l v. 21.1

a .munfiwvrlo .9 "u...ed....na..v¢._e.v....il .

- ‘l‘il'blu’lr— (.oil‘.’

Janna!" ‘1‘: it... v 7'. "H"... ”t...

n “U“ uvvnhpnu‘ EHJMDJRP?! vnnlt
fir.“ ..

10?: pl»... 0!.

 

3 .u ,
’c' E

«5131'
e '7

W92'F1‘»
U 'a 1;"
23 'ufi'v

:‘3

he):
Iva-11.":
Ant?! .3
I 2 1.! pr .
‘33.

 

.‘3

in;

H:
.

W"

I.
D. -‘Ilfittuilél‘ 3...?
1|!" 1| »DOD\$|. til-t

F.\, 11. .

"H

 

o C
'1

IA. DID? t0

: . -,.‘ 2
’o”".'c"'
." e'
0”,4‘
n,¢§vf

‘2

 

.. 1. -. .
1 .b.:f..u.1
A 44 7 .- V
a. -233.-. ..

. ...

 

4.3.1.. nary .

.2315...“ :1 . .Il

 

, p . , . . f‘lllrhn
I 3 .aa 12.1»?

       

 

an‘i. .17. Y;
, L . ‘9r41.",1&.v.r-|0.|
. . . Us" I: 1.. u
. . . . ‘.!.I.I.y V.Avl"..l!lyb
4 ... ‘ . :...‘...-u.,
{’11:le : 1.... . x... 113.... . ..
3‘9... It: xtln... 17.1. I. 10......th 4E. .
. . .. . .1..i..€t-.1..0 :. : ‘.3
. .v.. I . . v t! ‘ Hogvl .71. L itllu‘-‘ I
I. A f .1... £0) 5...: 9.1.5.... .I. ‘ I o».)ill“l..h'l. ‘ I. .f ‘l
—”°v 1:3..' I cll . . x..f.§..l. ‘ . A ‘ T. .Plu . liluv. .‘ri v | ,
b "Y‘u Ir. 0 . ' ‘ 1| w -t u<..n . .
1.3.3.1. nu... .: .. ~15... ‘ . _ . 2. 1 f . ..H.L .v. . .
_ .uans llv fil“... Lu I. .vl’c Jvoo ciihn. :11! . ‘
t ‘ . . 94:. 1-01.‘ V‘l.(1u....o...olu.u... Jan ”5&7"? .v. y 0 . V
—J . I'll! b.Y..t....lo....ovr§1; .1. . .
cl .1! 03.]. n.‘ . y
. . .i 1 o. wanri|qt5txzz \ ulv. 0.
“.4 . .hal-"léujll‘flfl55w .‘4 . , ‘u ..

- ' ‘
I'll- l,

I II‘ [vilg
_ It! - I i

llllllll“Nullllllllllll \llllllllllll

 

 

 

 

31 29300
f \
LIBRARY
Michigan State
University
K I
This is to certify that the
dissertation entitled

ORGANOCLAY AS TRIPHASE CATALYSTS

presented by
Chi-Li Lin

has been accepted towards fulfillment
of the requirements for

Ph.D. degree in Inorganic Chemistry

%a/M/ fiat”: 0" ‘ W

j r professor

Date Aug 15 1988

 

MS U is an Affirmative Action/Equal Opportunity Institution 042771

 

 

 

 

 

 

PLACE N RETURN BOXto movomochockunfrom your mood.
TOAVOD FlNESMunonorbduoddodn.

DATE DUE DATE DUE DATE DUE

    
  

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

IIEQ

__J
[5%

 

 

 

 

 

 

 

 

MSU In An Ailinndlvo ActioNEqunl Opponmiiy Institution
Walla-9.1

 

ORGANOCLAY AS TRIPHASE CATALYSTS

By
Chi-Li Lin

A DISSERTATION

Submitted to
Michigan State University
in partial fulfillment of the requirements
for the degree of
DOCTOR OF PHILOSOPHY
Department of Chemistry

1988

ABSTRACT

ORGANOCLAY AS TRIPHASE CATALYSTS

By

Chi-Li Lin

A new type of triphase catalysts has been synthesized by intercalation of
quaternary onium cations in smectite clays. These clay-supported phase transfer
catalysts, as well as other triphase catalysts, are easily recovered by filtration and ideally
suited for continuous flow methods. However, the onium-ion functionalized smectite
clays have certain advantages over conventional tn'phase catalysts: i) they are stable
under reaction conditions and provide efficient interfacial surfaces for the catalysis of
organic reactions. ii) their catalytic prOperties are comparable to analogous biphase

catalysts. iii) they can avoid using polar solvent in the catalytic process.

The mechanistic investigation of this organoclay catalysis for alkylbromide
displacement has indicated that the reaction mixtures form an oil-in-water emulsion in
which the organoclay plays an essential role in stabilizing the emulsion. Three
fundamental kinetic steps of the organoclay catalysis have also been proposed. In
additional, the organoclays have been applied to a variety of useful synthetic

transformations in which the organoclays were shown to be more efficient than the

analogous polymer-supported phase transfer catalysts. The catalytic properties of several
commercial organoclays and organo-layered compounds were also studied in comparison

with those of our organoclay.

Furthermore, the intercalation of chiral phase transfer cations in smectites has
developed a new series of triphase chiral catalysts. The stereoselectivity and mechanism
of these organoclays in the borohydride reduction of ketones and in the epoxidation of
chalcone were studied. Although a great deal of research needs to be. done before the
kinetic steps of clay-supported chiral catalysis can be proposed. It has to be emphasized
that the clay-supported chiral catalysts are pracncally superior to conventional biphase
catalysts. Moreover, for a given chiral cation we are able to alter its Optical selectivity by

intercalating the cation on various clay hosts.

TO MY FAMILY

iv

Acknowledgments

I would like to thank Dr. 'I'J. Pinnavaia for his guidance and support though my graduate

study and to Dr. CH. Brubaker for his guidance in editing this dissertation and Dr. N.

Jackson and CK. Chung for helpful discussions.

My special gratitude is extended to my family for their encouraging support.

I also would like to thank all past and present group members for the friendship.

TABLE OF CONTENTS

Chapter Page
LIST OF TABLES ....................................... VII
LIST OF FIGURES ........................................ X
CHAPTER I. INTRODUCTION
A. Structure and Properties of Layered Silicates ....................... 1
1. Structure .......................................... 1
2. Ion Exchange ....................................... 3
3. Swelling and Catalytic Properties
of Smectites ....................................... 3
B. The Principles of Phase Transfer Catalyst ......................... 9
1. The Nature of Phase Transfer Catalyst ........................ 9
2. Mechanism of Phase Transfer Catalysis ...................... 10
3. Applications of Phase Transfer Catalysis ...................... 12
4. Systems Related to Phase Transfer Catalysis ................... 12
a) Reactions at the interface ............................ 12
b) Micelle-Catalyzed Reactions .......................... 12
C. Some AspeCts of Chiral Phase Transfer Catalysis ................... 13
1. Nature of Chiral Phase Transfer Catalysis ..................... l3
2. Mechanism ....................................... 13
a) Epoxidation of Elecrron.Poor Olefins ..................... 19
b) Borohydride Reductions ............................. 19
3. Other Reactions .................................... 22
D. Development of Triphase Catalysis ........................... 22
1. Nature of Triphase Catalysis ............................. 22
2. Polymer. Supported Phase Transfer Catalysis ................... 32
a) Mechanism .................................... 35
b) Applications of Polymer-Supported Phase
Transfer Catalysts ................................ 3S
3. Inorganic.Based Catalysis .............................. 35

a) Synthesis, Structure Characteristics
and Behavior of Inorganic.Based Phase

Transfer Catalysts ................................ 36
b) Mechanism and Applications .......................... 38
4. Polymer-Supported Chiral Phase

Transfer Catalysts ................................... 38

a) Nature of Polymer-Supported Chiral
Phase Transfer Catalysts ............................ 38
b) Mechanism and Applications .......................... 39
E. Research Objectives ..................................... 4 4

vi

Chapter Page
CHAPTER II EXPERIMENTAL

A. Material ............................................ 46
1. Natural Sodium Hectorite ............................... 46
2. Laponite R ....................................... 46
3. Fluorohectorite ..................................... 47
4. Reagents ......................................... 4 7
B. Preparation of Organoclay Phase Transfer
Catalysts ........................................... 48
C. Preparation of Clay-Supported Chiral catalyst ..................... 48
D. Organoclay Phase Transfer Catalysis ........................... 4 9
E. The Applications of Organoclay Phase
Transfer Catalyst 1n Organic Synthesis ......................... 50
1. Synthesis of Ethers .................................. 50
2. Oxidation of Benzyl Alcohol ............................. 50
3. Synthesis of n. Pentyl Thiocyanate ......................... .51
4. Synthesis of Dipentyl Sulfide ............................ 51
5. C-Alkylation of Benzyl Cyanide .......................... .51
6. Dehalogenation of vis. Dibromides ......................... 51
7. Halogen Exchange ReaCtion ............................. 52
8. Blank Reactions and Control Reactions ...................... 52
F. Comparison of the Catalytic Pr0perties of
Organoclays ......................................... 52
G. Comparison of the Catalytic Properties of .
Some Organo-Layered Compounds ........................... 53
H. Asymmetric Reduction of Ketones ............................ 53
I. Asymmetric Epoxidation of Chalcones ......................... 54
J. The Determination of Enantiomeric Excess
of Reaction by 1H NMR .................................. 55
K. Physical Measurements .................................. .55
1. Infrared Spectroscopy ................................. 55
2. X-ray Diffraction Studies ........................ . ....... 55
3. Gas Chromatography ................................. 56
4. Proton NMR Spectroscopy .............................. 56
5. Specific Rotation .................................... 56
6. Orbial Shaking Water Baths ............................. 56

vii

Chapter Page
CHAPTER III RESULTS AND DISCUSSION
A. Preparation of Organoclay Phase Transfer

Catalysts ........................................... 57
B. The Catalytic Properties of Organoclays 1n
Alkylbromide Displacement by Cyanide Ion ...................... 63
The Dependence of Catalytic Reactivity on
the Loading of Onium Cation ............................ 64
2. The Dependence of Catalytic ReaCtivity on
the Molecular StruCture of the Onium Cation ................... 69
3. The Dependence of Catalytic Reactivity on the
Molecular Structure of the Organic Substrates ................... 7 S
4. The Dependence of Catalytic Reactivity on the
Concentration of Substrates and Catalysts ............. ' ........ 75
5. The Dependence of Catalytic Reactivity on
the Layer Charge of Clay Host ............................ 76
6. The Dependence of Catalytic Reactivity on
the Polarity of Organic Solvent ......... L ................. 84
7. The Mechanism of Organoclay Catalysis
in Alkylbromide Displacement by Cyanide Ion .................. 88
C. Organic Synthesis Catalyzed by Organoclay ...................... 88
1. Synthesis of Aromatic Ether from Phenol ..................... 91
2. Oxidation of Alcohols ................................. 94
3. Synthesis of Alkyl Thiocyanate ........................... 94
4. Synthesis of Sulfide .................................. 94
5. C—alkylation of Nitriles ................................ 99
6. Dehalogenation of vic.Dibromides ......................... 100
7. Halogen Exchange .................................. 100
D. Comparison of the Catalytic Properties of
Organoclay ......................................... 100
E. Comparison of the Catalytic Properties of
Some Organo-Layered Compounds ........................... 108
F. Preparation of Clay-Supported Chiral Catalysts .................... 112
G. The Stereoselectivity and Mechanism of Organoclay
in the Asymmetric Reduction of Ketones ....................... 112
l. The Dependence of Enantiomeric Excess on
the Layer Charge of Clay Host ........................... 115

2. The Dependence of Enantiomeric Excess on
the Molecular Structure of Chiral Cation

and Organic Substrates ................................ 121
3. The Dependence of Enantiomeric Excess on
the Concentration of Catalyst and Substrates ................... 123

viii

Chapter Page

4. The Dependence of Enantiomeric Excess

on the Temperature .................................. 130
5. The Dependence of Enantiomeric Excess on
the Polarity of Organic Solvent ........................... 131
6. Conclusion ....................................... 131
H. The Stereoselecdvity and Mechanism of Organoclay
in Asymmetric Epoxidation of Chalcones ....................... 132
1. The Dependence of Enantiomeric Excess on
the Layer Charge of Clay Host ........................... 135
2 The Dependence of Enantiomeric Excess on
the Temperature .................................... 136
3 The Dependence of Enantiomeric Excess on
the Polarity of Organic Solvent ........................... 143
4. The Dependence of Enantiomeric Excess on the
Concentration of Chalcone ............................. 144
5 The Dependence of Enantiomeric Excess on the
Volume Ratio of Aqueous and Organic Phases ................. 144
6 Conclusion ....................................... 145
CHAPTER IV RECOMMENDATIONS .......................... 151

ix

LIST OF TABLES
TABLE Page

1. Products Formed by Ion Exchange Reaction
of Hexadecyltrimethylammonium Chloride
with Na+-Hectorite and Their Activity for
Triphase Catalysts ..................................... 71

2. Produc1s Formed by Ion Exchange Reac1ion
of Tetrabutylammonium Chloride with
N a+—Hectorite and Their Acrivity for
Triphase Catalysts ..................................... 72

3. Homoionic Organohectorites as Phase
Transfer Catalysts for the Displacement
Reaction of Alkylbromide with Cyanide ........................ 73

4. The Dependence of kobs Values on Alkyl
Chain Length for Conversion of .
Alkylbromides to Cyanide ................................ 77

5. Dependence of kobs Values on Potassium
Cyanide Concentration for Conversion of
Pentylbromide to Pentylcyanide ............................. 78

6. Dependence of kobs Values on Organoclay
Concentration for Conversion of

Pentylbromide to Pentylcyanide ............................. 81
7. Dependence of kobs Values on the Clay Host for
Conversion of Pentylbromide to Pentylcyanide .................... 85

8. Dependence of kobs Values on the Polarity
of Organic Solvent for Conversion of

PentylbromidetoPentylcyanide. . . . . . . . . . . . . . . . . . . . .. ....... 86
9. Synthesis of Phenyl n-Pentyl Ether ........................... 95
10. Oxidation of Benzyl Alcoho ............................... 96
11. Synthesis of n-Pentyl Thiocyanate ........................... 97
12. Synthesis of n-Dipentyl Sulfide ............................. 98
13. C-Allrylation of N itriles ................................. 101
14. Dehelogenation of vie-Dibromides .......................... 102

TABLE Page
15. Synthesis of Alkylchloride from Alkylbromide ................... 103

16. Infrared Data and 1H NMR Data for the Products
by Organoclay Triphase Catalysis ........................... 105

17. Catalytic Reactivities of Commercial
Organoclay in the Synthesis of
n-Pentylcyanide from n-Pentylbromide
under Triphase Reaction Conditions .......................... 109

18. Catalytic Reacrivities of Organolayered
Compounds for the Synthesis of
n-Pentylchloride from n-Pentylbromide under

Triphase Catalysis Conditions ............................. 110
19. X-ray Basal Spacings Data of Clay-supported

Chiral Catalysts ...................................... 113
20. Infrared Data and 1H NMR Data for

Benzyl t-Butyl Ketone .................................. 116
21. The Blank Reactions of Borohydride

Reduction of Butyl Phenyl Ketone .......................... 120

22. Asymmetric Borohydride Reduction of
Phenyl Ketones in the Presence of
Clay-Supported Chiral Catalysts ............................ 124

23. The Dependence of Excess Enantiomer on
the Concentration of Clay-Supported
Chiral Catalysts in Asymmetric Borohydride
Reduction of Ketones .................................. 129

24. The Dependence of Enantiomeric Excess on
Temperature in Asymmetric Borohydride
Reduction of Ketones with Clay-Supported
Chiral Catalysts ...................................... 133

25. The Dependence of Enantiomeric Excess on
the Polarity of Organic Solvent in
Asymmetric Borohydride Reduction of Ketones
with Clay-Supported-Chiral Catalysts ......................... 134

26. Dependence of Enantiomeric Excess on the
Molecular Structure of Chiral Catalysts
for Asymmetric Epoxidation of Chalcone
with Clay-Supported Chiral Catalysts ......................... 138

27. The Blank Reaction of Epoxidation of Chalcone .................. 139

xi

TABLE Page

28. Dependence of Enantiomeric Excess on
the Layer Charge of the Clay Host for
Asymmetric Epoxidation of Chalcone with

Clay-Supported Chiral Catalysts ............................ 142
29. Dependence of Enantiomeric Excess on the .

emperature for Asymmetric Epoxidation of

Chalcone with Clay-Supported Chiral Catalysts ................... 146

30. Dependence of Enantiomeric Excess on
the Polarity of Organic Solvent for
Asymmetric Epoxidation of Chalcone ........................ 149

31. Dependence of Enantiomeric Excess on the
Concentration of Substrates and Volume
Ratio of Aqueous and Organic Phase for
Asymmetric Epoxidation of Chalcone with
Clay-Supported Chiral Catalysts ............................ 150

xii

 

 

 

|
1C

LIST OF FIGURES

FIGURE

10.

The schematic structure of a 2 : l

diocmhedral aluminum silicate minerals ..............

The schematic structure of a 2 : 1

trioctahedral magnesium silicate minerals .............

Smectite clays classification .....................

The mechanism of phase transfer catalysis

with 8N2 displacement reactions ...................

Chiral phase transfer catalysts : salts of
quinine (a-f), salts of ephedrine (g-j), 8 S. 9
R-quinine (k), 8 S, 9 R-cinchonidine (l), 8 R,

9 S-quinidine (m) and 8 R, 9 S-cichonine (n) ..... h .......

Preferred conformation of benzquuinium
cation (1)

Preferred conformation of benzquuinium
cation about C4-C9 bond (A and B)
Preferred conformation of benzquuinium

cation about C3-C9 bond (C and D) (63, 64) ............

The transition states for asymmetric
epoxidation of cyclohexenones catalyzed

by (-) N-benzquuininium cation (63) ................

Asymmetric methylation of 6,7-dichloro-
5-methoxy-2-pheny1-l-indanone catalyzed by
8-R, 9-S, N—(p-trifluoromethyl benzyl)
cinchonium bromide catalysts (the catalyst

structure is in the Figure 5f) (73) ...................

Asymmetric alkylation of 2-carbomethoxy-
l-indanone catalyzed by chiral crown ethers
(67) and quinine (The catalyst structure

is in Figure 51:) (63, 74) ........................

Michael addition of thiols to a B
unsaturated ketones catalyzed by
cinchonidine (The catalyst Structure is

in Figure 51) (63. 75) ..........................

xiii

Page

........... 4

........... 6
........... 8

..... 11

......... 14

......... 17

......... 20

......... 23

......... 24

......... 26

FIGURE Page

11. 2+2 Cycloaddition reaCtions catalyzed
by quinidine (The catalyst structure
is in Figure 5k) (63, 76) ................................. 27

12. Asymmetric epoxidation of electron-poor
olefins catalyzed by benzyl quininium
chloride (The catalysts structure is in
figure 5a) (63, 83-69. 77-78) .............................. 28

13. The process of triphase catalysis for
8N2 displacement reacrions ............................... 30

14. The mechanism of polymer..supported phase
transfer catalysis : a) mass transfer or
reactant form bulk liquid to the surface
of the catalyst particle b) diffusion of
reactant through the polymer matrix to the
active sites. c) intrinsic reaction at the
active sites, d) diffusion of product through
the polymer matrix to the particle surface
and e) mass transfer of product from the
surface of the catalyst to the bulk solution.
A Phosphonium substituted catalyst is used for
illustratioon here, but this basic mechanism can
apply to most polymer-supported-supported PT C’s ................. 33

15. Alkyl-functionalization of silica gel
and alumina ........................................ 37

16. The strucmre of polymer..bound alkaloids
(AC) and polymeric amines (DE) (48) ........................ 40

17. The mechanism of Michael addition catalyzed
by polymer-bound cinchonal alkaloids (48) ...................... 42

18. Schematic representation of onium cation
intercalation in smectite clay .............................. .58

19. Arrangements of alkylarnmonium ions in the
layer silicates with different loading of
the onium cation. 3) very low cation
loading b) medium cation loading c) high
cation loading d) homoionic compound ........................ 60

20. A combination system of sodium hectorite
and homoionic organoclay ................................ 62

xiv

FIGURE Page

21. The three..component system toluene/ water/
hectorite supported [C16H33PBu3]+ is
presented by mass ratio at room
temperature. 0 , emulsion;A, wet solid
pastem, gel;o , suspension;
I, emulsion with extra toluene ............................. 65

22. A proposed model for the uniform
organoclay colloid emulsion formed under
triphase reaction conditions ............................... 67

23. Dependence of kobs values on potassium
cyanide concentration for the conversion
of pentylbromide to pentylcyanide
catalyzed by [C16H33PBu3]+-hectorite ........................ 79

24. Dependence of kobs values on organoclay
concentration for conversion of
pentylbromide to pentylcyanide catalyzed
by [C 16H33PBu3]+-hectorite .............................. 82

25. The fundamental kinetic steps of the
organoclay in the alkylbromide displacement
by cyandie ion : i) the organic substrates
are attracted to the alkyl chain of catalysts
by hydrOphobic interaction. and the inorganic
anions are attracred to the polar end of
catalysts by electrostatic interactions
ii) displacement reaction occur in the
emulsion phase. iii) the products are
transferred from the emulsion phase back to
the organic phase or aqueous phase ........................... 89

26. The 1H NMR Spectrum of n..butyl phenyl
alcohol (0.06 M in CDC13) in presence of
various amount of chemical shift reagent
Eu(hfc)3. The molar ratios of chemical
shift reagent and the alcohol are 0. 0.32,
0.43, 0.52 and 0.87 in (a)-(e), respectively ...................... 117

27. Configuration of (-) Epoxychalcone .......................... 137

28. The possible conformation of
transition state epoxidation of
the chalcone catalyzed by 151AA ........................... 140

29. The hypOthesis of the dependence of
the reaction rate on the temperature
A) Epoxidation of chalcone by F151AA
B) Epoxidation of chalcone by 15 1AA ....................... 147

XV

Chapter I

INTRODUCTION

A. Structure and Properties of Layered Silicates

1. Structure

The layered silicate described in this dissertation belongs to a Class of clay
minerals known as smectite. The term" clay minerals" refers to specific structural types
silicate with particle size less than 2 11m and with a definite stoichiometry and crystalline
structure. Recent advances in X-ray crystallography and structural analysis have
affirmed that completely ordered clay structures represent no more than ideal models
(1,2).

Smectites are composed of units made up of two silica tetrahedra sheets and a
central octahedral sheet of magnesia or alumina. The silicate tetrahedral are usually
oriented so that the three basal oxygen atoms of each tetrahedron lie on the same plane,
while the fourth oxygen atom defines a second common plane. The octahedral sheet
contains a cation, usually Al or Mg, surrounded by six oxygens in an octahedral
arrangement. The tetrahedral and octahedral sheets are combined so that the tips of the
tetrahedrons of each silica sheet and the oxygens of the octahedral sheet form a common
layer. Smectite clays are 2:1 layer minerals which are divided broadly into two structures

: dioctahedral aluminum silicate minerals (Figure 1) and trioctahedral, magnesium

2

silicate rrrinerals (Figure 2). These can subdivided into groups in which the layer charge
arises predominantly from isomorphous substitution in the octahedral layer and from
substitution in tetrahedral layer. Further subdivisions can be made on the basis of layer
charge density (Figure 3). Cations at particular locations of the silicate structure can be
replaced by various Other cations with similar ionic radii without changing the structural
characteristics of the mineral. If the replacing cation has a lower valence, a net negative
charge will develop. Charge neutrality is achieved either by an opposing substitution
with cations of higher valence or, as is usually the case, by the presence of additional
cations, normally, arrays of hydrated alkaline earth or alkali metal cations in the
interlayer region of the structure. The charge balancing cations are usually located
adjacent to the points of anionic charge on the basal planes. However, small anhydrous
cations, mainly H+ or Li+, can migrate through the oxygen sheet to the neighborhood of
the substitution, where the anionic charge arises. Hectorite, Laponite and Fluorohectorite
are the three smectites of principal interest in the present work. The idealized unit cell

composition for hectorite is

Mo.67[Mgs.33Li0.67lV1(Si8.o)1V020(0H.F)4

in which the superscripts (IV) and (VI) refer to the respective cation in tetrahedral and
octahedral sites, and M represents a univalent or equivalent compensating cation (1).
The commercial filler, Laponite is a synthetic low-charge hectorite (about 0.4 e- per
Ozo[OH,F]4) which, unlike the natural mineral, can be obtained with a negligible iron
content. Fluorohectorite is anOther synthetic high-charge smectite (about 1.8 e- per
020F4) in which the octahedral lattice hydroxyl groups have been replaced with fluoride

ions. The idealized unit cell composition for Laponite and Fluorohectorite are

Lio.36[LiO.36M85.64](Si8.00)020(0H)4

Lil.6[Li1.6Mg4.4](5i8.00)020F4

Interlamellar spacings in general depend upon the species of exchangeable cation present,
the nature of solvent, and whether or not any electrolytes are present.
2. Ion Exchange

The hydrated compensating cations of minerals are exchangeable. However,
there is a size limitation for ion replacement. Hectorite, for example, exhibits an average
distance about 8.7 A between exchange sites based on the calculation of a cation
exchange capacity (73 milliequivalents per 100 g of air dried clay) and_the a and b unit
cell parameter of the mineral (5.25 x 9.18 A) (3). Thus, cations with cross-section
diameters greater than this value will fill the interlamellar spaces before an homoionic
clay is achieved. And although the interlamellar surface is very large (750 mZ/g), the
size of the exchanging ion can be a limiting factor in determining ion loading.

The kinetics and equilibria of the exchange reaction depend on several variables
(4,5). In general the exchange equilibrium favors a) cations with higher valence charge;
b) the larger cation between species of a particular valence. Certain cations because of
their size can take up a very favorable interlayer position. The rate of exchange reaction
is determined mainly by the swelling properties of the mineral, the nature and
concentration of cations. In smectite the position of exchangeable cations are about 80
percent on the basal plane surfaces, with the remainder on the edges.
3. Swelling and Catalytic Properties of Smectites

Smectite clays can be swelled by adsorption of water or organic solvent. With
multiple layers of solvents the galleries become liquid-like, and accessible for chemical
reactions. The osmotic swelling of smectite clays is limited by the electrostatic
interactions between the anionic silicate layers and compensating interlayer cations. As

the solvent content increases the basal spacings of smectite clays also increase. The

Figure 1.

The schematic structure of a 2 : 1 dioctahedral aluminum
silicate mineral

lnterloyer Region

AAI OO

©OH

'Si

Figure 2. The schematic structure of a 2 : l trioctahedral magnesium
silicate mineral

 

lnterloyer Region

AMQ OSi

00 ©OH

SMECTITE CLAYS

DIOCTAHEDRAL TRIOCTAHEDRAL
MONTMORI LLIONITE HECTORITE .
BEIDELITE - SAPONITE
NONTRONITE

Figure 3 Smectite clays classification

swelling and increases in basal spacing on treatment with solvent not only can be used
for identification of these minerals but also plays a very important role in catalytic
reaction as well.

In the last few decades, smectite clays and their derivatives have shown catalytic
activity in numerous reactions (68). Most of the reactions make use of the acidic nature
of cation-exchanged or acid treated clay. Both Lewis and Bronsted activity have been
noted, the former deriving from aluminum or iron species located at crystal edges (9).
The Bronsted activity, however, results either from free acid or from the dissociation of
interlayer water molecules coordinated to polarizing interlayer exchangeable cations.

Catalytic organic reactions have often been shown to take place in the
interlamellar space. We should expect, therefore, to find instances of unusual factors in
these reactions since they occur in a region of high acidity and possibly, in a restricted
2D reaction space.

B. The Principles of Phase Transfer Catalyst

1. The Nature of Phase Transfer Catalyst

Chemists frequently encounter the problem of bringing together two mutually
insoluble reagents in sufficient concentration to attain conveniently rapid reaction rates.
The traditional procedure would involve dissolving the reactants in a homogeneous
medium. But a suitable solvent is not always available and it is usually expensive and
difficult to remove after reaction and may present environmental problems in large scale
operations.

The technique of " phase transfer catalysis " can permit or accelerate reactions
between ionic compounds and organic, water-insoluble substrates in solvents of low
polarity (10-12). The basic function of the phase transfer catalyst is to transfer ions, free
radicals, neutral molecules, or even energy (in a chemical form) from one phase to
another. It is clear that PTC has considerable advantages over conventional procedures

since it can: a) remove the requirement for expensive anhydrous or aptotic solvents, b)

10
improve reaction rates, c) lower reaction temperatures, d) simplify work-up e) permit
reactions that do not proceed using conventional methods, 1') modify selectivity, and g)
increase yields.

Reactions involving phase transfer phenomena were performed since 1913 (13).
A considerable number of such reactions are buried in olderliterature (14-16) and
especially in patents (17-29) in which quaternary ammonium or phosphonium salts were
used as catalysts for two phase reactions. Since some of the authors entered the field
more or less incidentally and did not reflect on the mechanisms involved in such catalytic
reactions, few realized the potential and scope of the new technique.

PT C techniques as we know them today originated in the work of Makosza and
coworker in 1965 (30) and the term "Phase Transfer Catalysis" was coined by Starks and
first used in patents in 1968 (11). Although PT C has emerged only in the last decade it
already has become a widely useful synthetic technique.

2. Mechanism of Phase Transfer Catalysis

The mechanism of phase transfer catalysis varies to some extent with the type of
system involved (neutral, acidic or basic condition). All phase transfer catalyzed
reactions involve at least two steps: a) transfer of one reagent from its "normal" into the
second phase; and b) reaction of the transferred reagent with the nontransferred reagent.
For the simplest 8N2 displacement reactions the mechanistic pathway is illustrated in
Figure 4 (31, 32).

In this Figure Q+ represents an onium salt cation which forms an ion pair with
anion Y‘ in the aqueous phase and extracts the anion into the organic phase. Once the
anion has been transferred into the organic phase it reacts with RX and forms a new salt
[Q+X-]. The new salt [Q+X-] then returns to the aqueous phase, where Q+ picks a new
Y- ion for the next cycle. It is necessary to consider the mechanism by which the anion
is transferred when we study the system of phase transfer catalysis. There are several

possible mechanisms for the phase transfer step (33) : a) simple ion exchange across the

11

23:23. 505323...
«zm 5.2. 31.3.8 .832. 3a.... .0 ...».cagoo... 2; .e 932“.

omega
Amaoosc<v -X+O ... ->+21||I .X+2 ... ->+O

III'

......................... k. .

among
.2590. -X+O ... >mtlll. xm ... .>+O

12

interface; b) transfer of Q+ back and forth across the interface with anion exchange in
the aqueous phase; c) transfer of the inorganic salts into the organic phase for exchange
d) transfer of anion at the organic-crystalline solid interface (at SL systems) e) formation
of micelles in the; aqueous phase and transfer of anions across the micelle interface. PT C
as it being defined is not based on any mechanism. Hence, extensive investigations are
need to elucidate the mechanism of any PT C systems.

3. Applications of Phase Transfer Catalysis

Since the discovery of phase transfer catalysis, numerous applications have been
described (32—37), not only in organic chemistry, but also in inorganic chemistry (38),
analytical applications (39), electrochemistry (40, 41), photochemistry (42, 43), and
especially in polymer chemistry (44—50).

In organic synthesis PT C has emerged as a broadly useful tool for : a)
nucleophilic displacement reactions b) alkylation and condensation reactions c) reactions
of dihalocarbenes and other carbenes d) ylide-mediated reactions e) oxidation and
reduction reactions f) and various miscellaneous reactions. In those reactions the
technique of phase transfer catalysis provides a method which can avoid the use of polar
aprotic solvent and also improve the reaction rate. Although phase transfer catalysis has
suffered difficulties of separation at some later stage it appears to have high potential
along synthetic lines.

4. Systems Related to Phase Transfer Catalysis

:1) Reactions at the interface (51) Reactions occurring at an interface tend to be
rate limited by the amount of interfacial area available and are therefore highly sensitive
to the amount of agitation and concentration of reactant species at the interface.

b) Micelle-catalyzed reactions (52-54) Surfactant molecules possessing well
defined diphilic properties usually form small aggregations of 10-50 organic molecules
dispersed in the aqueous phase. These small aggregations are called micelles, wherein

the nonpolar organic part of the molecules occupy the internal volume while the highly

13
polar groups of the surfactant occupy the outer surface. The positively charged outer
surface attracts and concentrates anions from the bulk aqueous solution into a counter ion
layer near the surface of'the micelle and reaction may occur at the micelle surface.
C. Some Aspect of Chiral Phase Transfer Catalysis

In the recent literature three different approaches have been used for asymmetric
induction : chiral reagents (55, 56), chiral auxiliaries (57-62) and chiral catalysts (63-65).
The disadvantage of the first two methods with respect to an economical process is that
both are used in stoichiometric amounts and have to be recycled. Chiral phase transfer
catalysts offer a potentially simple, one step solution to this problem.

1. Nature of Chiral Phase Transfer Catalysis

Phase transfer catalysis involves ion pairs with a rather close association.
Therefore with strongly orienting chiral catalyst cations it is possible to obtain significant
asymmetric induction.

To date virtually all the work has employed onium salts based on ephedrine and
its relatives, the cinchona alkaloids and crown ethers (Figure 5). Some confusion still
remains in the literature concerning the effectiveness of these catalysts (66). However,
the recent results reported by Cram (67) show a great optical yield ( ~99%).

Two generalizations seem to be emerging in the area of phase transfer chiral
catalysis. An hydroxy substituent B to the quaternary ammonium center of the chiral
catalyst is required for significant enantioselectivity. The enantiomeric excess increases
with higher dilution of organic substrates, lower temperature, faster agitation and less
polar solvents. The concentration of catalyst controls the rate of reaction but to have
little effect on the enantiomeric excess.

2. Mechanism

In order to establish a reasonable mechanism of asymmetric induction it is

necessary to determine the preferred conformations of chiral phase transfer catalysts in

solution . At present, the accurate determination of ground-state conformations of the

14

Figure 5. Chiral phase transfer catalysts : salts of quinine (a-f), salts
of ephedrine (g-j), 8 S, 9 R-quinine (k), 8 S, 9 R-
cinchonidine (l), 8 R, 9 S-quinidine (m) and 8 R, 9 S-
cichonine (n).

15

 

 

 

nzo
...:aoazo azaoazo
«I Pm
Tu
«C F:
.x V‘\ I
":0. / K
foam. ...... ma
1 :0

 

nuoqruo ”zoo .
8 foo o
2.120.410 «:00 a
”10...... foo o
N02.2.0 nzoo ..
nzao £00 a
N... ...
..a
...
.00 N...
... \
m
.. ... H
J. z

 

 

16

.”:oo

”:oo

 

 

I
_. ..... who
.../2 a a .
m
I
I_
...
0 ...
«U. ...:
L

17

Figure 6. Preferred conformation of benzquuinium cation (I).
Preferred conformation of benzquuinium cation about C4-
C9 bond (A and B). Preferred conformation of
benzquuinium cation about C3-C9 bond (C and D) (63, 64)

OH

 

 

 

 

...»...
H

H o
C.

H H
.6 N.

19

chiral phase transfer catalysts in solution is rarely feasible. Nevertheless, several
preferred conformations of chiral catalysis in the transition state have been proposed by
Wynberg (63) and Dolling (64) (Figure 6). In the following the mechanism of two
particular reactions catalyzed by cinchona alkaloids will be discussed.

a) Epoxidation of Electron-Poor Olefins

So far the enantiomeric excesses (ee) obtained by using chiral phase transfer
catalysts in epoxidation reactions have not been exceedingly high, except in a few cases
(68,69). The reaction, however has a large scope and furnishes optically active epoxides
inaccessible by other routes. Because of the lack of kinetic data and the complexity of
phase transfer asymmetric catalysis it is very difficult to propose a mechanism.

Wynberg has presented a hypothetical mechanism for the cyclohexenone
epoxidation catalyzed by chalcone (63). By using a preferred conformation of the
benzquuininium salt (Figure 6), assuming a tight ion pair between the catalytic cation
and the peroxide anion with the hydrogen bonding between the hydroxyl of the alkaloid
and the carbonyl oxygen of the ketone he predicted a transition structure fitting the
description in Figure 7. When t-butyl hydroperoxide is the reagent, it forrrrs an ion pair
with the quinuclidine nitrogen of the alkaloid in a fairly compact structure. This t-
BuOO' quininium complex allows the approach of cyclohexenone or chalcone from one
side and favors one of two possible enantiomers only.

b) Borohydride Reductions

There are a few references on borohydride reductions of ketones with chiral
catalysts, mainly ephedrine and the cinchona alkaloids (68-71). These limited results
imply that the catalysts decomposed under the reaction conditions (66, 72), however the
decomposition is slow.

No detailed mechanisms have been proposed. But most research groups recognize
that the borohydride anion will form an ion pair with the catalyst cation, and the

interaction of the B hydroxyl of the catalyst with the ketone will favor one of two

20

Figure 7. The transition states for asymmetric epoxidation of
cyclohexenones catalyzed by (-) N-benzquuininium cation
63).

21

 

22
possible diastereomeric transition states. Further investigations are required before a
clear picture emerges in this system.
3. Other Reactions

The use of optically resolved catalysts for the direct synthesis of enantiomerically
pure compounds remains one of the dreams of the chemist. It would seem that chiral
phase transfer catalysts are particularly well adapted to this problem. Recently, Wynberg
and Dehmlow have written detailed reviews of the applications of chiral phase transfer
catalysis (34, 63).

Several successful applications of chiral phase transfer catalysts in asymmetric
reactions have been investigated. Dolling and his co-workers (73) demonstrated the
methylation of a substituted indanone in 95% yield and 92% ee by using 8-R, 9-S, N-(p-
trifiuoromethylbenzyl) cinchonium bromide as catalyst (Figure 8). For the Michael
reaction, Wynberg (63, 74) found an 87% yield with an cc of 76% by adding methyl
vinyl ketone (MVK) to 2-carbomethoxy-l-indanone catalyzed by quinine (Figure 9).
Later studies by Cram showed that ee’s approaching 99% could be obtained using chiral
crown ethers as catalyst (67).

Similarly Michael additions of thiols to a,b unsaturated ketones catalyzed by
cinchonidine obtained relatively high ee’s (Figure 10) (63, 75). The wide range of
enones and thiols potentially amenable to this reaction and the versatility of the sulfur
and carbonyl functionality (Figure 10) make this reaction useful in many ways. In Figure
11 it shows that a variety of aldehydes were able to react with ketene to form the
corresponding b-lactones in excellent chemical and nearly quantitative enantiomeric
yields (63, 76). Also chalcones (63, 77, 78), quinones (79-82) and cyclohexenones (83)
are epoxidized successfully to optically active epoxyketones and epoxyquinones by 30%

hydrogen peroxide,t-buty1hydroperoxide, and 28% sodium hypochlorite (Figure 12).

23

 

cr 7)
CI H NaOH, Solvent
.-
CH X, PTC
01130 3
cr 0
Cl CH3
ee : 92 °/o
c1130
Figure 8. Asymmetric methylation of 6,7-dichloro-S-methoxy-Z-phenyl-1-

indanone catalyzed by 8-R, 9-S, N-(p-trifluoromethylbenzyl)
cinchonium bromide catalysts (the catalyst structure is in the Figure 5f)
(73).

24

Figure 9. Asymmetric alkylation of 2-carbomethoxy-1-indanone
catalyzed by chiral crown ethers (67) and quinine (The
catalyst structure is in Figure 5k) (63, 74).

25

$2.

.xbm

"zoo. :ouazo
__
o

20 m3. magi; __

559.0 ..mm P

EEO nzouoo

 

VS... azoaoo

   

\
o

¥>2

26

 

O
0
R Clnehonidlne
R SH . / ;
3' Solvent
0
R!
R S
RI
Figure 10. Michael addition of thiols to a B unsaturated ketones catalyzed by

cinchonidine (The catalyst structure is in Figure 51) (63, 75).

27

 

0 fl Quinidine
II I
Q—CHZ - c - c1 * CCI3CH -
Toluene
-4o°c
o
//
QC" -<=
l |
H - c — o

ccr3

enantiomeric excess > 95%

Figure 11. 2+2 Cycloaddition reactions catalyzed by quinidine (The catalyst
structure is in Figure 5k) (63, 76)

28

Figure 12. Asymmetric epoxidation of electron- poor olefins-catalyzed
by benzyl quininium chloride (The catalysts structure is in
figure 5a) (63, 83-69, 77-78)

29

 

 

OH
I
....
b ,
O
I R none
0‘ b i
ll
0

R4
Hz a. Q
mo eonc
“3
II
o b

BONC

: benzquulnlnlum
chloride

: 30% H202 10% NaOH,
or t-BuOOH,
or 28% NaOCI

30

Figure 13. The process of triphase catalysis for 3N2 displacement
reactions.

 

31

 

 

 

E . ..x

xx + ...,
>m 030m -x

xx ..>

 

U_Z<om0 mDOmDO<
.- L

mains—.40 mm<In:m._.

 

32
D. Development of Triphase Catalysis

1. Nature of Triphase Catalysis

A new type of heterogeneous catalysis, termed "triphase catalysis", has recently

been introduced (84), in which the catalyst and each one of a pair of reactants is located

in separate phases. Figure 13 illustrates the general features of a simple displacement

reaction of a triphase catalyst system.

In general, the reactivity of triphase catalysts is lower than that for a comparable
biphase catalytic process. But triphase catalysis makes the catalyst recovery processes
facile, and from the practical point view, it is very attractive. Also, the low energy, and
capital requirements for processing, together with its ideal suitability for continuous flow
methods, give triphase catalysis appears to have great potential as a versatile technique in
organic synthesis.

Several triphase catalysrs have been attempted previously by bonding of biphase

transfer catalysts to some polymers (84-99) or inorganic supports (100-105, 106-108).

The general application of these catalysts is still under investigation.

2. Polymer-Supported Phase Transfer Catalysis

Polymer-supported phase transfer catalysts are the first and the best studied
triphase catalysts that have been employed. This approach originally showed great
promise for solving two important PT C deficiencies : lowering catalyst cost by recycling
and eliminating residual catalyst in the product. But this promise has not been realized
because in the polymer-supported phase transfer catalysis, the reaction rates are limited

by diffusion processes which have recently been reviewed by Ford (44, 45).
a) Mechanism

There is considerable debate concerning the mechanism of polymer-supported
phase transfer catalysis in liquid-liquid systems (94, 96, 109-112). In general, the

fundamental kinetic steps for polymer-supported phase transfer catalysis are as follows

(Figure 14): a) mass transfer of reactant from bulk liquid to the surface of the catalyst

Figure 14.

33

The mechanism of polymer-supported phase transfer
catalysis : a) mass transfer or reactant form bulk liquid to
the surface of the catalyst particle b) diffusion or reactant
trough the polymer matrix to the active sites, c) intrinsic
reaction at the active sites, d) diffusion of product through
the polymer matrix to the particle surface and e) mass
transfer of product from the surface of the catalyst to the
bulk solution. A Phosphonium substituted catalyst is used
for illustration here, but this basic mechanism can apply to
most polymer-supported-supported P'I'C’s.

 

34

 

 

35

particle, b) diffusion of reactant through the polymer matrix to the active sites, c) reaction
at the active sites, (1) diffusion of product through the polymer matrix to the particle

surface, e) mass transfer of product from surface of the catalyst to bulk solution. The

same five fundamental kinetic steps must occur in catalyst regeneration.

The major disagreement is whether the reaction occur in an aqueous solvation

shell, at an organic-aqueous interface (111, 112) or in an organic solvation shell (94, 96,

109, 110) within the polymer (Figure 14 step (c)) . No clear conclusion has been

reached. Probably different polymer (e.g. chloromethyated,crosslinked polystyrene or
commercial anion exchange resin ) and different supported phase transfer catalyst (e.g.
onium cation, crown ether, cryptand, polyethylene glycol, phosphoric acid amide,

phosphonic ester amine oxide or aza-crown ether) will cause changes in the reactive site
from a hydrophilic to hydrophobic shell.

b) Applications of Polymer-Supported Phase Transfer Catalysts

Recently synthetic applications of polymer-supported phase transfer catalyst have

been reviewed by Dehmlow & Dehmlow (34). But none of them has found any

industrial applications because polymer-supported phase catalysts generally suffer from

diffusion limitation, gradual loss of activity and mechanical instability. A new type of

polymer-supported phase catalyst called "chiral polymeric phase transfer catalyst" has

been under investigation since 1978 (113). But none of these more results are

satisfactory due to the fundamental problem involving diffusion through the polymeric
matrix (113-119).

3. Inorganic-Based Catalysis

So far there are only a few reports describing the study and use of inorganic-based
triphase catalysts. Silica gel or alumina (55, 100-103, 106-108, 120), Aerosil-‘200 or
aminoalkyl Corning Glass (121) and clay (104, 105) are three general types of inorganic
supports that have been used. These inorganic-based triphase catalysts show different

properties from the corresponding onium salts supported on polymer matrices. Because

36

different inorganic matrices having different chemical structures, surface area, size and
geometries of the micropores are differently functionalized, there is not any general
mechanism that can apply to those systems. The following sections will focus on silica
gel and alumina as inorganic supports.

a) Synthesis, Structure Characteristics and Behavior

of Inorganic Based Phase Transfer Catalysts

The synthesis of these supported onium salts starts from the anchoring of an
alkyltrialkoxysilane (either a haloalkyl or arninoalkytrialkoxysilane) on the surface of
silica gel or alumina to afford the alkyl functionalized inorganic matrix (Figure 15).
However, the surface of silica gel or alumina needs to be activated before the anchoring
process by refluxing with 35% hydrochloric acid to transform the strained siloxane
linkages into free OH groups.

The degree of functionalization of alumina is less than that of silica gel, consistent
with the fact that the surface concentration of hydroxyl groups is lower in alumina than in
silica gel (0.1-2.5 OH / nm2 and 4-10 OH / nm2 respectively). The linkage between the
inorganic matrix and the organic function is very stable under acidic conditions but is less
stable to base. For examples, 6OSiC3NH3+Br (0.89) loses 43% functionalization after
24 hours in aqueous 0.1N NaOH at room temperature (108) (where 608i indicates that
silica gel with a mean pore diameter of 60 A is the matrix, C3 indicates the length of the
alkyl chain supporting the ammonium salt, and the value in parenthesis represents the
loading as millirnoles of the counterion of the onium salt per gram of catalytic support).

The exact structure of these systems during catalysis remains unknown and not all
the questions concerning the disposition of the aqueous and organic phases in the
functionalized pores have been answered. The major advantage of silica gel or alumina-
based triphase catalysts is that under liquid-liquid phase transfer catalysis these systems
can catalyze reactions without being stirred and do not need the use of polar solvent.

This catalysis is not controlled by diffusion but by the regeneration of the catalytic

 

 

37

 

 

OH /--OH
A1203 "‘3' é—OH
5'02 0 Reflux é—OH
/
Silica gel or Activated Silica gel
Alumina or Alumina
RSl(OR)3.

7—°\

/—o—sm

; o/

/

 

Aikyi-functlonalized
Silica gel or Alumina

Figure 15. Alkyl-functionalization of silica gel and alumina

38

centers and the long alkyl chains of catalytic centers act as an anion pump between the
aqueous, organic phases, both of which are present in the third solid phase.
b) Mechanism and Applications

A general mechanism similar to those for polymer-supported phase transfer
catalysts are operate in these systems. However, the diffusion steps are replaced by the
adsorption of the organic substrate and desorption of organic products on the matrix. The
precise mechanism of these systems during catalysis remains unknown, due to the
complex nature of the interactions of the inorganic salts, organic species and solvents
within the different domains of the functionalized support.

Various applications concerning the use of silica gel or alumina-based triphase
catalyst in nucleophilic substitution reactions have been reported : halogen exchange
(101, 102, 106), synthesis of alkyl chlorides from alcohols (101), synthesis of phenyl
ethers and sulfides (101), reduction of carbonyl compounds with aqueous sodium
borohydride (101), synthesis of nitriles, thiocyanates (103) and N-alkylphthalimides
(106). Depending on the reaction conditions, however, the functionalized inorganic
matrices could lose some of their functionalization during some reactions. Then,
reactions were actually catalyzed both by the phase transfer catalyst and the silica gel or
alumina-based triphase catalysts as well as the hydrolysed catalytic groups .

4. Polymer-Supported Chiral Phase Transfer Catalysts

a) Nature of Polymer-Supported Chiral Phase Transfer Catalysts

The use of polymer-supported chiral phase transfer catalysts for asymmetric
synthesis has increased significantly in recent years, and there are a number of reviews

concerning this topic (48, 122-123).

In order to prepare an effective polymer-supported chiral phase transfer catalyst
there are several requirements that have to be met : i) The polymer support must be
compatible with the reaction solvent as well as being chemically, thermally and

mechanically stable under the reaction condition. ii) The rate of the catalytic reaction

 

 

39

should not be appreciably diminished and the chemical selectivity and enantiomeric
excess should be at least comparable to the homogeneous analog. However, high
enantiomeric excesses have not be obtained under the triphase systems. Nevertheless, the
experiments confirm that the solution reactions can be translated successfully into the
supported system.

The polymer supported chiral phase transfer catalysts can be divided into two
main classes: polymer-bound alkaloids and polymeric amines (Figure 16). By varying
the loading of chiral phase transfer catalyst on the polymer, the nature of the polymer
backbone (polar or nonpolar), the nature of the chiral phase transfer catalyst and degree
of cross-linking of the polymer, one is able to design an effective polymer-supported
chiral phase transfer catalyst for a particular utilization.

b) Mechanism and Applications

So far the enantiomeric excesses obtained by using polymer-supported chiral
phase transfer catalysts are lower than those obtained by using the analogous
homogeneous chiral phase transfer catalysis, except in few cases. Both Chiellini and
Kobayashi have showed that the steric course of the reaction catalyzed by cinchona
alkaloids is dominated by the configurations of C-8 and G9 in the alkaloids and by the
nature of the C-3 group only in the case of bulky substituted alkaloids (48, 124, 125).
Figure 17 shows the reaction mechanism in Michael type addition in the presence of
polymer-supported cinchonal alkaloids. A multicenter transition state involving the
activated double bond, the nitrogen atom and the hydroxyl group is proposed. Although
little promise of supported chiral phase transfer catalysts has appeared, the optimism

remains. Furthermore recent work has attempted aim to exploit the chiral functional

polymer as a chiral reagent

40

Figure 16. The structure of polymer-bound alkaloids (A-C) and
polymeric amines (D-E) (48).

41

«33:6
_

.m. z
\ An: «:0

_
13.0 . :o . _._z+

 

 

 

 

 

 

42

Figure 17. The mechanism of Michael addition catalyzed by polymer-
bound cinchonal alkaloids (48). '

 

 

43

+ 68.85%... i

O
...
_
o
o

3:330

_ _

 

 

 

 

ll

 

 

 

 

 

am— «I
/ \ .
G ..olo/l m 1
ohms . z
. /
. c
I m. I
_ _
fl?
0 ... a .5259.
a u
m m
/o .. o\
\ /
o u o z
u /.
... m z
_ p
O n: max .5332;

 

44

E. Research Objectives :

Smectite Clays as Phase Transfer catalysts

Phase transfer catalysis has found use both in research and commercial
applications because of its advantages of simplicity, mild reaction conditions, and high
efficiency. One serious disadvantage of phase transfer catalysts is that they are very
expensive and difficult to remove from the reaction mixture at some later stage. Also,
phase transfer catalysts sometimes form undesirable emulsions and do not lend
themselves to convenient chemical processing methods.

Triphase catalysis has been developed to solve these problems. From the point of
view of industrial applications, these triphase catalysts are very attractive due to being
easily recovered by filtration and ideally suited for continuous flow methods. The
triphase catalysts developed to date make use of polymer or inorganic matrices (e.g.,
silica gel, alumina, glass). Polymer supported phase transfer catalysis is sorrretimes
limited by diffusion of reaction substrates to the polymer matrix and suffers from the
necessity to use polar solvent. Inorganic based phase transfer catalysts are not stable
under mild basic reaction conditions and lose functionalization at room temperature.
Borh of polymer and inorganic-supported phase transfer catalysts have lower catalytic
reaCtivity and higher manufacturing costs than comparable soluble phase transfer

catalysts.

Smectite clays, having an ordered layer structure, provide certain advantages over
polymer and inorganic matrices as phase transfer catalysts supports. This study has
shown that onium-ion functionalized smectite clays are stable under various reaction
conditions and provide efficient interfacial surfaces for the catalysis of organic reactions.
There is no need to use polar solvents in clay-supported phase transfer catalysis and the

catalytic reactivity of the clay-supported phase transfer catalysts is comparable to

analogous biphase transfer catalysts.

 

 

45

The main objeCtive of this study was to explore different approaches to
intercalated clay phase transfer catalysts and to investigate the mechanism and the
applications of clay-supported phase catalysts.

The first part of this work examines the dependence of onium cation loading and
the catalytic reactivity of clay-supported onium catalysts. Also, in order to study the
mechanism of clay-supported phase transfer catalysis in a nucleophilic displacement
reaction several parameters controlling the efficacy of these triphase systems have been
investigated (e.g., the structure of substrates and supported onium cations, the
concentrations of substrates and catalyst, the layer charge of the clay support and the
polarity of the organic solvent). In this part the triphase catalysis technique has been
expanded by applying it to variety of other useful synthetic transformation.

In the last few years, polymer-supported chiral phase transfer catalysis for
asymmetric induction has received a great attention for the growing demand for optically
pure compounds in the pharmaceutical and agro-chemical industries. The success of
clay-supported phase transfer catalysts inspired the idea of studying the clay-supported
chiral phase transfer catalysts. Thus, the second part of this dissertation describes the
preparation and study of clay-supported chiral phase transfer catalysts.

The mechanism of borohydride reduction using clay-supported chiral phase
transfer catalysis has been examined by studying the dependence of enantiomeric excess
on several experimental parameters (e.g., the structure of the supported chiral catalyst
and substrates, the concentration of catalyst and substrates, the layer charge of the clay
support, the reaction temperature and the polarity of the organic solvent). Further
applications of clay-supported chiral phase transfer catalysts in epoxidations of

unsaturated ketones have also been examined.

46

Chapter II

EXPERIMENT

A. Material
1. Natural Sodium Hectorite

Naturally-occurring California sodium hectorite with a particle size less than 2
run was obtained from the Source Clay Mineral Depository, University of Missouri, in
the pre-centrifuged and spray dried form. The mineral was purified by removing
carbonates and free iron oxides according to procedures described in the literature (126).

The idealized anhydrous unit-cell formula of hectorite is
Nao,67[Lio,67Mg5,33(Si8,oo)Ozo(OH,F)4] and experimentally determined cation-
exchanged capacity is about 73 meq. / 100g of air dried clay.
2. Laponite R

Synthetic hectorite with a structural formula of
Lio,36[Lio_36Mg5,64(8i8,00)Ozo(OH)4] was obtained from Laporte Company, England
and was used as supplied from the manufacturer. The particle size of this mineral is
approximately 2 run with a cation exchange capacity around

55 meq. / 100g of air dried clay.

47

3. Fluorohectorite

This synthetic hectorite was donated as an aqueous suspension by Corning Glass
Works USA and used without further purification. In this mineral the octahedral lattice
hydroxyl groups have been replaced by fluoride ions. The unit cell formula is
Lil,6[L11,6Mg4.4(813,00)020F4]. The mineral has a particle size less than 2 um and
cation exchange capacity of approximately 125 meq. / 100 g air dried clay.

4. Commercial Organoclay and Organo-Layered Compounds

Commerical organoclay, Benton 34, was donated by Baroid Co. and the ECCT
organoclay series was obtained from English China Clay Co.. Layered compounds were
synthesized by Ahmad Moini according to literature techniques and intercalated with
onium ions using procedures analogous to the intercalation of organoclays (127-137)

5. Reagents

All onium salts were obtained from Chemical Dynamics Corporation and Aldrich
Chemical Company. (-) N-dodecyl N-methylephedrinium bromide and tris[3-
(heptafluoropropyl-hydroxymethylene)-(+)-camphorato], europium (III) derivative
(Eu(hfc)3) were obtained from Aldrich Chemical Company. (-) N-benzyl quininium
chloride was obtained from Fluka Chemie. All Other organic and inorganic reagents and
organic solvents were obtained from Aldrich Chemical Company. All reagents and
organic solvents were ACS grade and were used as obtained except ethyl ether and
absolute alcohol (138, 139).

Phenyl t-butyl ketone was synthesized as described in ref. 138 : The Grignard
reagent was prepared from 0.32 mole of magnesium, 0.34 mole of bromobenzene and
250 ml of ether distilled from phosphorus pentoxide. Without cooling, pivalonitrile (0.33
mole) was added rapidly to the Grignard reagent solution. The solution was then
refluxed and the mixture was poured onto cracked ice mixed with 20% hydrochloric acid
and allowed to stand overnight for complete hydrolysis. The phenyl t-butyl ketone was

extracted with ether and the extracts being washed further with water, saturated sodium

48

bicarbonate solution and then dried with sodium sulfate and distilled at reduced pressure
(138). The 1H NMR and FT IR spectra of product (T able.20) were identical with those
of authentic samples.

Synthesis of (+) n-benzquuinidium chloride was conducted as described in ref.
139 : Fifty mmole of quinidin was dissolved in a mixture of 50 ml benzene and 10 ml
ethanol and allowed to stand at room temperature with 50 mole of benzyl chloride for
26 hr. The solvent was evaporated and product was washed with pentane and
recrystallized from absolute alcohol which was purified as in ref 139.
B. Preparation of Organoclay Phase Transfer Catalysts
l. A 0.5 wt% aqueous suspension of a sodium hectorite was stirred vigorously for
24 hr with a known amount of an tetrabutyl ammonium or hexdecyltributylphosphonium
salt dissolved in water or methanol solution (0.073M). The products were washed free of
excess onium salt with ethanol, resuspended in deionized water, collected by
centrifugation, and air dried at room temperature. In order to study the loading of onium
ion corresponding to the number of onium ion equivalents used in the reaction the meq.
ratios of onium ion to clay employed ranged from 0.25 to 10.0. The products were then
examined by X-ray diffraction (Table 1 and 2 samples 1AA-14AM).
2. A 1.0 wt% aqueous suspension of smectite clay was stirred vigorously for 24 hr
with 2 cation exchange capacity (CEC) of alkylarnmonium or alkylphosphonium salt
dissolved in water or methanol solution (0.073M). The products were washed free of
excess onium salt with ethanol (testing by bromide or chloride electrode), resuspended in
deionized water, collected by centrifugation, and air dried at room temperature. The
products were examined by X-ray diffraction (Table 3 Samples 15AA-26AM and Table 7
Samples L18AA, F18AA, L22AA, F22AA, L26AA, F26AA).
C. Preparation of Clay-Supported Chiral catalyst

In a typical experiment, a 1.0 wt% smectite clay aqueous suspension was added to

a vigorously stirred aqueous solution containing of 2CEC chiral onium salt ((-) N-

49

dodecyl N-Methylephedrinium bromide or (-) benzyl quininium chloride ) (0.073 M).
After 24 hr of reaction, the products were washed free of excess chiral onium salt with
ethanol (monitored by a polarimeter), resuspension in deionized water and air dried at
room temperature. The products were examined by X-ray diffractiometer (Table 19
Samples 131AA, F131,151AA and F151AA).

D. Organoclay Phase Transfer Catalysis

General Methods.

The reactions of alkyl bromides with potassium cyanide under triphase conditions
were canied out as follows: The air dried organoclay phase transfer catalyst was
dispersed in 3.0 ml aqueous solution of potassium cyanide in a 15 x 150 mm pyrex
culture tube with magnetic stirring bar and fitted with a teflon screw cap. After the
mixture was Stirred for a few hours 2.0 mmole alkylbrorrride and 0.5 ml decanc as
internal standard were added in 6 ml of toluene or other organic solvent. The tubes were
immersed in an oil bath maintained at 90.0 i 0.5°C and reaction rates were determined
by withdrawing 1 111 samples from the upper excess organic layer and analyzing the
products mixtures by GLC (see section K. Physical Measurements for details of
instrumentation used). The reproducibility of the observed rate constants were high and
the errors are within 5%. Pseudo first-order rate constants were calculated with a least-
squares program.

Similar methods were used in Studying the reaction rates under biphase
conditions, except that an appropriate amounts of onium salts were used in place of the
organoclay phase transfer catalyst. Parameters which have been investigated to control
the efficacy of organoclay phase transfer catalyst are listed as follows: 1. Loading of
intercalated onium cation; 2. Molecular structure of intercalated phase transfer catalysts;
3. Molecular structure of substrate; 4. Concentration of organoclay and potassium

cyanide; 5. Layer charge of clay host; and 6. Polarity of solvent.

50

E. Applications of Organoclay Phase Transfer Catalyst

in Organic Synthesis

In the following reactions the [MeN(C3H17)]3+-hectorite (25AA) and
[Bu3PC16H33]3+-hectorite (26AA) were utilized as catalysts. The stabilities of
organoclays in the reaction condition were examined by the X-ray d-spacing of the
recovered catalysts and the control reactions described below.
1. Synthesis of Ethers

To a Coming no. 9826 culture tube containing 0.05 mmole of organoclay phase
transfer catalyst was added to 2.5 M sodium hydroxide solution (6ml), followed by 10
mole pentyl bromide, 5 mole phenol and 0.5 ml of decanc as internal standard. The
tube was placed in an oil bath maintained at 90 i 05°C for the time indicated in Table 7.
The reaction mixtures were quenched to room temperature by cooling with an ice bath.
The catalyst was removed by filtering and the chemical yields were determined by
withdrawing 1 111 samples from the upper organic layer of the filtrate and analyzing the
product mixtures by GLC. The organic layer was then extracted by ethyl ether, washed
with 2.5 M sodium hydroxide solution, neutralized by sodium bicarbonate solution and
dried over sodium sulfate. The product was collected by distillation and analyzing by FT
IR, and 1H NMR (Table 7 and Table 16).
2. Oxidation of Benzyl Alcohol

Organoclay phase transfer catalyst (0.05 mmole) was dispersed in 5 ml of 10%
aqueous sodium hypochlorite in a Corning no. 9826 culture tube. After the mixture was
stirred for 2 h, 1.0 mole of benzyl alcohol dissolved in 2 ml toluene and 0.5 ml of
decanc as internal standard were added. The tubes were immersed in an oil bath
maintained at 50 i 05°C for the time indicated in Table 8 and the reaction mixtures were
cooled rapidly to room temperature by use of an ice bath. The catalyst was removed by
centrifugation or filtering and the chemical yield were determined by withdrawing 1 111

samples fiom the upper organic layer of the filtrate and analyzing the product mixtures

51

by GLC. The organic phase was extracted with ethyl ether and dried over sodium
sulfate. The product was collected by distillation and analyzed by analogous procedure
to the procedures described above (Table 8 and Table 16).
3. Synthesis of n-Pentyl Thiocyanate

Organoclay phase transfer catalyst (0.05 mole), sodium thiocyanate (10
mole), 2 ml of water 0.5 ml of internal standard, decane, and n-pentyl bromide (5.0
mmole)were added to a Comin g 9826 culture tube and placed in a oil bath maintained at
90 i 05°C. The reaction times were given in Table 9 and the analogous procedure as
above was performed in the determination of the chemical yield and the purification of
the product. The product was analyzed by FT IR and 1H NMR (Table 9 and Table 16).
4. Synthesis of Dipentyl Sulfide

Organoclay phase transfer catalyst (0.05 mmole) was mixed with 0.5 ml decanc,
3.0 ml of water containing dissolved sodium sulfide (6.0 mole) and l-bromopentane
(5.0 mole). The mixtures were Stirred vigorously at 90 :i: 0.5 0C for 0.5 hr. The
emulsion was broken by centrifugation and the same workup procedure as above was
used for the determination of chemical yield and product collection. Analogous analysis
as above was used to identify the product (Table 10 and Table 16).
5. C-Alkylation of benzyl cyanide

Organoclay phase transfer catalyst (0.05 mmole) was added to a culture tube
containing decane (0.5 ml) 1-pentyl bromide (5.0 mmole), benzyl cyanide (5.0 mole)
and 50% sodium hydroxide solution (2.0 ml). Reaction temperature was maintained at
50 :i: 0.5°C for the time indicated in Table 12. Product was collected by the usual
workup procedures and analyzed by GLC, FI‘ IR, 1H NMR (Table 12 and Table 16).
6. Dehalogenation of vis-Dibromides

Organoclay phase transfer catalyst (0.05 mmole) was mixed with 2.0 ml of water
containing dissolved sodium iodide (0.264 mole) and sodium thiosulfate (32.0 mmole)

and toluene (2.0 ml) containing dissolved 1,2-dibromo-l,2-diphenyl ethane (1.0 mmole).

U1
IQ

After vigorous stirring for the reaction time indicated in Table 13 at 90 :i: 05°C the
emulsion was broken by centrifugation, and product was obtained and analyzed in the
similar procedure (Table 10 and Table 16).
7. Halogen Exchange Reaction

Organoclay phase transfer catalyst (0.05 mmole) was added to 6 ml of toluene
containing n-alkyl bromide (2.0 mole) and 3 ml of water containing sodium chloride
(6.67 mrrrole). Reaction temperature was maintained at 90 :t 05°C for the time indicated
in Table 14 and emulsion was broken by centrifugation. Similar collection and analysis
procedure of product was used (Table 15 and Table 16).
8. Blank Reactions and Control Reactions

Each blank reaction was run under the same condition as described except
without using catalyst. Each catalyzed reactions was repeated for controlled reaction in
the same procedure, except that the catalysts were removed by filtration after half the
reaction time and the reaction was continued under the same procedure with the filtrate.
The recovered catalyst was washed with ethanol and water and X-ray d001 Spacing were
measured. The stabilities of organoclays in the reaction condition were proved by the
retention of d-spacing of recovered catalysts, and the discontinuation or slowdown of the
reaction after the filtration of catalysts.
F. Comparison of the Catalytic Properties of Organoclay

The catalytic properties of a series of commercial organoclay (Benton 34, ECCT
40, ECCT AF and ECCT PS) were investigated in cyanation reactions. The triphase
conditions were carried out as follows : Commercial organoclay (0.13 g) was dispersed in
3.0 ml aqueous solution of potassium cyanide (20.0 mmole) in a Corning no. 9826
culture tube. After the mixture was stirred for 2 h 2.0 mmole n-pentylbromide and 0.5 ml
decanc as internal Standard were added in 6 ml of toluene. The reaction mixtures were
placed in an oil bath maintained at 90 i 05°C. The reaction times are indicated in Table

17. The reaction mixtures were quenched to room temperature by cooling with an ice

53

bath. The catalyst was removed by filtration. The organic layer was then extracted by
ethyl ether, washed with 2.5 M sodium hydroxide solution, neutralization by sodium
bicarbonate solution and dried on sodium sulfate. The chemical yield of product was
determined by GLC.
G. Comparison of the Catalytic Properties of Some

Organo-Layered Compounds

The catalytic properties of some organo-layered compounds were examined for
bromide displacement both by cyanide and by chloride. The cyanation was carried using
analogous procedures as in commercial organoclay except that 0.1 g of organo-layered
compound was used. However, all of the organo-layered compounds in these Studies
underwent de-intercalation or decomposition under the cyanation reactions as indicated
by the X-ray data for the recovered catalysts. The triphase reaction conditions for
chloride displacement of alkylbromide are performed as follows : Air dried organo-
layered compound (0.1 g) was added to 6 ml of toluene containing n-alkylbromide (2.0
mole) and 3 ml of water containing sodium chloride (6.67 mole). Decane (0.5 ml)
was also added as internal standard. The reaction temperature was maintained at 90 :l:
0.5°C for the time given in Table 18. Product was collected and purified by usual
workup procedure. The chemical yield of reaction was determined by GLC.
H. Asymmetric Reduction of Ketones
1. In a typical experiment, potassium borohydride (3 mole), 0.25 mole ketones
(phenyl t-butyl ketone or phenyl n-butyl ketone), benzene (6 ml), water (5 ml), and clay-
supported chiral catalyst were mixed in a flask and Stirred at various temperatures for
suitable times. The reaction was followed by GLC and catalyst was separated by
filtering. The aqueous phase was extracted with benzene and the combined organic
fraction were dried over sodium sulfate. After the evaporation of the solvent, the residue
was examined by FT IR, 1H NMR, GLC and polarimetry. Enantiomeric excesses were

determined by 1H NMR spectroscopy with Eu(hfc)3 as chiral shift reagents.

54

The parameters which have been studied to control the optical purity of products
were as follows : 1. Layer charge of clay support; 2. Structure of chiral catalyst; 3.
Structure of carbonyl compound; 4. Concentration of substrates and clay-supported
chiral catalyst; 5. Reaction temperature; and 6. Polarity of solvent.

2. Blank reaction

Blank reactions 1 and 2 in Table 21 were run using analogous procedures to those
described above except that clay-supported chiral catalysts were not used. The reaction
mixtures consisted of 6 mmole potassium borohydride dissolved in 5 ml of water and 3
ml of benzene solution containing 0.25 mmole phenyl n-butyl ketone and phenyl t-butyl
ketone respectively at 40C.

In order to examine the degree of desorption of chiral cation inside the gallery and
decomposition of the clay-supported chiral catalysts under the reaction conditions,
similar reactions were run without carbonyl compounds and catalyzed by. 131AA ((-) N-
Dodecyl N-Methyl ephedrinium hectorite), F131AA ((-) N-Dodecyl N-Methyl
ephedrinium F-hectorite), 151AA ((-) N-Benzquuininium hectorite), and F151AA ((-) N-
Benzquuininium F-hectorite) in blank reactions 3, 4, 5 and 6 respectively (Table 21).
After three reaction days the organic phases were collected and purified as described
before and examined by polarimetry. The stabilities of the organoclays under the
reaction conditions were proved by the absence of specific rotation of the reaction
residues when no carbonyl compound was used.

I. Asymmetric epoxidation of chalcones

The reactions were performed as follows : 0.48 mmole chalcone dissolved in
benzene or other organic solvents (3 ml), 1.5 ml of 30 wt% H202 , 1.5 ml of 12 wt%
NaOH and 0.2 mmole homoionic clay-supported chiral catalyst were mixed with a
magnetic stirring bar in a flask placed in a orbit shaker with speed 360 rpm at various
temperatures. The reaction was followed by TLC and the catalyst was separated by

filtration from the reaction residues after the reaction was completed. The aqueous phase

55

was extracted with benzene, and the organic fraction were combined and dried over
sodium sulfate. After the evaporation of the organic solvent at reduced pressure, the
residue was examined by FT IR, 1H NMR and polarimeter. The enantiomeric excess
was determined by 1H NMR with Eu(hfc)3 as a shift reagent.

Several components were investigated to control the enantiomeric excess of
epoxychalcone : 1. Molecular structure of intercalated chiral catalysts; 2. Layer charge
density of clay host; 3. The reaction temperature; 4. The polarity of organic solvents; 5.
Concentration of chalcone; and 6. Volume ratios of aqueous and organic phases. '

J. The Determination of Enantiomeric Excess of Reaction by 1H NMR

Shift reagents, introduced in 1969, provide a method for the determination of
molecular Structures. The shift reagents, in general, are ions in the rare earth series
coordinated to organic ligands. Addition of Shift reagents to appropriately functionalized
samples can result in substantial magnification of the chemical shift differences of
nonequivalent protons. The cre set the group of interest coordinations to the functional
group, the greater is the shift per increment of shift reagent. In a typical experimental
procedure 0.4 ml CDCl3 solution containing 0.6 M alcohols or epoxychalcones were
prepared at 0.87 mole ratio [mole of chemical Shift reagent Eu(hfc)3 per mole of alcohols
or epoxychalcone].

K. Physical Measurements
1. Infrared Spectroscopy

Infrared spectra were recorded on a IBM Single beam FT IR44 model
spectrophotometer. Solution Spectra were obtained by using 0.1mm NaCl cells and solid
spectra were recorded by mixing the samples with KBr and pressing them into disks.

2. X-ray Diffraction Studies

X-ray d001 basal Spacings were determined for oriented film samples with a

Philips X-ray diffractometer by using Ni-filtered Cu-Ka radiation ( 7. (Ka) = 1.5405 A).

The film samples were prepared by allowing an aqueous suspension of the samples to

56

evaporate on a microscope glass slide and monitoring the diffraction over a 29 ranging
from 20 to 450. The peak positions in the angle 20 were converted to d-basal spacing
with a standard chart.
3. Gas Chromatography

All product mixtures along with solvent and internal standards were analyzed by
gas-liquid chromatography on a Hewlett-Packard model 5880A with a flame ionization
detector and a capillary 25 m x 0.25 mm crosslinked dimethylsilicone column with GB-l
liquid phase and 0.25 11m film tickness. The output of the detector was recorded on high
Speed printer/plotter with key Stroke programme for data handling system. Products were
identified by comparison of GLC retention times with those of an authentic sample. The
percentage yield of products was determined by integration of the chromatographic peaks
of starting reagents and internal standard. Integrations were carried out by the dual
channel integration and computation, cartridge tape units, and BASLIC programming.
4. Proton NMR Spectroscopy

Proton nuclear magnetic resonance Spectra were recorded on a Bruker WM-250
MHz spectrometer. Chemical shifts were usually measured relative to tetramethyl silane
as an internal standard and are reported in units of ppm.
5. Specific Rotation

All specific rotations were measured on a Perkin-Elmer Co. model 141
polarimeter with sodium D line (5890 A) or mercury line (5780 A, 5460 A) at room
temperature.
6. Orbit Shaking Water Baths

The shaker used in this study are orbit shaker models 3545 from Lab-Line
instruments Inc. The Shaker Speed were ranging form 25 to 400 rpm and temperature

control has platinum RTD sensor within :1: 0.05 °C error.

57

Chapter III

RESULTS AND DISCUSSION

A. Preparation of Organoclay Phase Transfer Catalysts

The reaction of sodium hectorite in aqueous suSpension with various amounts of
hexadecyltrimethyl ammonium salt dissolved either in water or methanol results in
products in which the sodium ion is displaced by hexadecyltrimethyl ammonium ion
(samples 1AA-7AA and 1AM-7AM). Analogous products are obtained by reaction of
the aqueous sodium hectorite with tetrabutylammonium salt in water (samples 8AA-
14AA) or methanol (samples 8AM-14AM). For both types of reaction conditions, the
displacement of sodium ion by onium ions was strongly favored. Nearly complete cation
exchange was achieved by using stoichiometric amounts of reagents. The use of a two to
ten fold excess of onium ion assured complete cation exchange and formation of a
homoionic product. Figure 18 represents the exchange reaction, wherein the negatively
charged silicate layers have thickness of 9.6 A.

Table 1 and Table 2 illustrate, respectively, the d-spacing of a series of various
cation loadings of hectorite-supported hexadecyltrimethyl ammonium and hectorite-
supported tetrabutyl ammonium cations. The d-spacing of clay-supported
hexadecyltrimethyl ammonium cation increases as the amount of onium ion used

increases until the organoclay becomes a homoionic product. This could be explained by

58

Figure 18. Schematic representation of onium cation intercalation in
smectite clay

 
   

9':

 

1 3+

60

Figure 19. Arrangements of alkylammonium ions in the layer silicates
with different loading of the onium cation cation. a) very
low cation loading b) medium cation loading c) high cation
loading d) homoionic compound

61

 

 

 

 

 

 

 

 

 

8.

_o o o_.

a a
+ :2... +12

 

a a
ex: ea:

....l...

.5

 

 

 

re 6 om

§3¢2+ +3
.... +amz/\/\I\.1\/\

_o o o.

 

 

 

62

 

[o o as 9 9|

1. 9’ +
mt Na’ Na” Na Na Na

 

lo 9 9 99 9|

+ NR "’ +
NH: 3 "33+ NH3

 

Figure 20. A combination system of sodium hectorite and homoionic organoclay

63

the fact that the loading of organoclay increase as the number of onium ions used
increases until it reaches the cation exchange capacity, then even by using the excess
onium cation will not increases the loading of onium cation. The crowding caused by
increasing of the loading may alter the orientation of the long alkyl chain of onium cation
inside the gallery from parallel to perpendicular relative to the a, b plane of clay host.
Thus, an increase in the d-spacing with increasing loading is expected (Figure 19).
Besides the mixed cation product (Figure 19 A-C), a combination of sodium hectorite
and homoionic product is another possible system (Figure 20). This combination syStem
would result in a similar dependence of d-spacin g on the cation loading. However, the d-
spacing of hectorite-supported tetrabutyl ammonium cations are independent of cation
loading. Since the tetrabutyl ammonium cation has four equivalent alkyl chains,
changing the orientation of the cation dose not affect the d-spacing.

A series of onium ion exchanges form of hectorite was prepared using similar
procedures (Table 3). For a given onium cation, samples were prepared either in an
aqueous system (samples given a AA designation) or in an aqueous methanol system
(samples given in AM designation). Both methods resulted in analogous organoclays
with Similar d001 spacing and catalytic aCtivity (Table 3) .

B. The Catalytic Properties of Organoclays in Alkylbromide

Displacement by Cyanide Ion

The catalytic activity of each organoclay under "triphase" reaction conditions was
established by determining the pseudo first-order rate constant, kobs. for the reaction of
an alkylbromide in organic solvent (toluene) with potassium cyanide in aqueous solution
to yield a nitrile. A similar method was utilized in Studying the catalytic reactivity under
"biphase" conditions, except that the onium ion was dissolved in solution rather than
being supported in clay galleries. The blank reactions that were conducted under
conditions without catalyst (Table 1 and 2, blank 1) or with sodium hectorite as catalyst

(Table 1 and 2, blank 2) showed little or no catalytic reactivity.

64

These studies found that the more reactive triphase reaction mixtures formed
uniform organic liquid-water-clay colloidal emulsions. The results, along with the
catalytic activity data discussed below, demonstrated that organoclays which formed
emulsions under triphase reaction conditions were more active than those which did not.
Hence, organoclays which formed emulsions were the materials of choice for efficient
triphase catalysts. The emulsions are relatively Stable and need a long time to break on
their own. However, they were easily broken by low speed centrifugation or by filtering.

Under typical reaction conditions, all three phases will enter into emulsion
formation of the oil-in-water type. The clay phase plays an essential role in stabilizing
the emulsion, making it more effective than the biphase mixtures formed without
organoclay. More water can be added to the emulsion without the water separating from
the emulsion. However, if more organic phase is added to the emulsion it will separate
from the emulsion as a separate liquid. These observations along with a phase diagram
of toluene-water-organoclay (Figure 21) prove that the reaction emulsions are organoclay
stabilized organic liquid droplets dispersed in an aqueous phase. The emulsion is indeed
a triphase system, consisting of two liquid phases and a solid phase (Figure 22).

l. The Dependence of Catalytic Reactivity on the Loading

of Onium Cation

Table 1 and Table 2 Show the pseudo first order rate constants for conversion of
pentylbromide to pentylcyanide catalyzed by samples 1AA-14AA and 1AM-14AM under
triphase reaction conditions. The catalytic activity of hectorite-supported onium ions
increases as the loading of catalytically active onium ion increases. The optimum
reaction rates were obtained with the homoionic exchange forms of the clay ( sample
4AA-7AA, 4AM-7AM, llAA-14AA, 11AM-14AM). Swelling clays having as few as
about 25% of the inorganic exchange ions replaced by onium ions were catalytically
active, but homoionic derivatives in which all of the exchange ion were onium ions were

preferred.

65

Figure 21. The three-component system toluene/ water/ hectorite
supported [C16H33PBu3]+ is presented by mass ratio at
room temperature. 0 , emulsion;A , wet solid paste;A. gel;e
, suspension;e,emulsion with extra toluene.

66

mCmDHOF

 

1 k P p _ L _
code C 4 o e e
oeee e a e
IOCC 4 a a a O».
044 4 e 4
add a e 4 ON
at a e e
e c
o 1 e Om;
0‘ 4 4
4 e o
. . . . 0..
o
o e
0 ¢ cm
4
o
O O 4 om
oo
o
oo 0 ON
0
o

009
pounds

67

Figure 22. A proposed model for the uniform organoclay colloid
emulsion formed under triphase reaction conditions.

68

 

omega
maooaca

69

The hectorite-supported hexadecyltrimethylammonium ion having as little as
about 50% loading of onium cation exhibit an ability to stabilize an emulsion of the
reaction mixtures. In contrast, in the hectorite-supported tetrabutylammonium ion system
the triphase reaction mixtures spontaneously separated into different phases upon
cessation of stirring.

The catalytic activities of hectorite-supported hexadecytrimethylammonium ion
and tetrabutylammonium ion are not expected to be linearly related to the loading of
onium cation inside the gallery, because a substantial factor of the reaction occurs at
external rather than internal surfaces. Increasing the loading of onium cations will
increase the total cation sites in the organoclay and this will enhance the ability of
organoclay to form a stabilized emulsion. The emulsion forming ability is also
influenced by the clay particle size , the nature of the onium ion, the orientation of the
onium cation and the degree of onium cation loading. The difference in the PTC activity
for the hectorite-immobilized hexadecyltrimethylammonium ion and the
tetrabutylammonium ion are probably related to the difference in a combination of these
factors. For the hectorite-supported tetrabutyl ammonium ion system, the organoclay
showed a poor catalytic performance even in its homoionic exchange form (Table 2).

2. The Dependence of Catalytic Reactivity on the Molecular

Structure of the Onium Cation

There are two basic requirements for a phase transfer catalyst for nucleophilic
substitution : the catalyst must be a cation with enough organic structure to transfer the
desired anion into the organic phase; the effective cation-anion bonding must be "loose"
enough to allow high anion reactivity. However, the intrinsic biphasic activity of the
onium ion does not play a determinative role in the catalytic activity of their
corresponding triphase catalytic systems, because the triphase systems involve a different

reaction mechanism from that of the biphase system.

70

For instance, [BU4N]+, [(C12H25)2NMe2]+ and [C16H33PBu3]+ salts are
known as efficient phase transfer catalysts. However, in the triphase system clay-
supported [Bu4N]+ exhibited a poor catalytic properties being only 0.13 times as active
as the unsupported catalyst (Table 3, samples 18AA, 18AM) while clay-supported
[(C12H25)2NMe2]+ and [C16H33PBu3]+ retained their catalytic properties. On the
contrary, [C16H33NMe3]+ and [C14H29NMe3]+ which are poor phase transfer catalysts
in biphase system, were about 2.2 and 2.0 times more active when they were clay-
supported, respectively (Table 3, samples 19AA, 19AM and 20AA, 20AM). Thus, the
clay environment can substantially moderate the properties of onium ions as phase
transfer catalysts.

A survey of clay-supported onium ions as catalysts in the conversion of
pentylbromide to pentylcyanide is illusuated in Table 3. Equivalent reaction conditions
were investigated for both triphase and biphase systems. Values in parentheses are kobs
values determined under biphase conditions. In most cases the kobs values under
triphase conditions were lower than those under biphase reaction conditions, except for
the hectorite-supported hexadecyltrimethylammonium ion and tetradecyltrimethyl
ammonium ion systems which were more active than the corresponding biphase catalyst.
However, the convenience and efficiency of recovery of the organoclay catalyst more
than compensated for the reduced activity of the onium ion.

The phase transfer catalytic activity of the immobilized onium ion derivatives
does not correlate linearly with their d001 spacingis or with the intrinsic activity of the
onium ion as a biphase catalyst (Table 3).

The homoionic onium ion exchange forms of hectorite which formed uniform
emulsions under triphase reaction conditions (Table 3, samples 19AA through 26AM) are
more active than those which did not (Table 3, samples 15AA through 18AM). In these
studies one observed that the organoclay with onium cations containing a long alkyl

chain (samples 19AA through 26AM) can function as an emulsion former while the

 

71

 

.8... 0.5.0 ...... ... 330.00 8 08.. 0.03 080.00.. 8308 m
.8... 0.5... 0.... ... 03.. 0.03 :0. 82:0 ..0 >20 02 m

..e.ee.8_.-+.mm=e.ozmeze 38505 0 ... ... use; .8 ...m 5

025.8 833.80.. 0.088 0.0m ”0:030. .8 0 ... 00.80.00.800 0.088 0.~ .00.... 0.03 08030. 083000.. 2F
.0000 .0 0.8... 0800008800 0... 0. 008000.003 ..0 80.80800 00.. 88800 0.8 .080 .8... 0000.... w.
3.0 0.0. 00.0. 0.00. - 00m .25.
02.0 0.... 00.m 0.0m - 00m 320
mm. .0 0.0. 00.N 0.0m - 00m E<n
w. . .0 0.... 00.. 0.0. - 00m 25..
30.0 0.0. 2.0 n... - 00m 2<m
08.0 ..3 0n .0 06 - 00m E<~
0.0.0 0.: mad Om - 00m 3...:
0m. .0 0.... 00.0. - 0.00. 00.... <<>
0m. .0 0.... 00.m - 0.0m 00m <<0
mm . .0 N0. 00.~ - 0.0N 00m <<n
0m . .0 >6. 00. . - 0.0. 00m <<v
80.0 ...: 3.0 - m6 00m <<m
0.0.0 0.2 0m .0 - 06 00m <<~
000.0 0.... 2.0 - ma .00N <<.
.000 0 0 - - - - mm 0.5.5
000.0 - - - - - 0. 0.5:.

1... 6.60.0 .30 008 .0552: ... .803 ... 00.03 ...
maroo. 5-02 111018200 08 :0. 8.8.0 ..0. 83:0 080.02.-..2 0008....
.9...me < .000 2 2.0.0 .8 2 20.0 .8 00.3 .020 .8

 

 

89.300 3020...... 00.. .0300... 00.... 0.... 0....0.0om-+az 5.3 0.0.0020
8380880150883003xom 00 000003. 00:20.6 ..0. .... 00800". 80:00.0 . 0.0a...

72

 

 

...... ....0... 0.... ... 50.0.00 m0 000... 003 0...0.00.. 80.000 0
...... 0.00... 0.... ... 08.. 003 ..0. 8.....0 .0 00.0 07. .1.
..0...0.00..-+_Z0..m0 00.000090 0 0. .0 £0.03 .8 0.m ...
00.0000 83000.00 0.088 00~ ”0:0...0. .8 0 ... 00.80.00.800 0.088 00 .00.... 0.03 0.00000. 0832.0. 0:...
.0000 .0 0.8... 05000000800 0... 0. 00.80.00.800 ..0 00.0.0800 .0. 80.800 0.0. .00.0 .8... 00:80 0
000.0 0.0. 00.0. 0.00. - 00a 20.0.
000.0 0.0. 00... 0.0m - 000 2<m.
000.0 0.0. 00.0 0.0m - 00m SEN.
0000 0.0. 00.. 0.0. - 00m 2.... .
000.0 0.0. n 0.0 m .0 - 00m 2.00.
0~00 0.0. 0w .0 00 - 000 .2<0
.000 0.0. 30 Wm - 00.0 .>.<w
0m00 0.0. 00.0. - 0.00. 000 <<0.
0000 0.0. 00.m - 0.0m 00m «JR.
300 ..n . 00.0 - 00m 00m <<m.
30.0 ..n. 00.. - 0.0. 00.0 <<..
N000 0.0. n00 - n .0 000 <<0.
0.00 0.0. 0w .0 - 0.n 00m <<0
m000 0.0. 20 - ON 00m <<w
.000 0 0 - - - - mm 0.00.0
000.0 - - - - - .1. . 0.0....
. .... .0..00.0 00.0 008 .0..0...08 ... .203 ... .0.03 ...
...er.. 0.0...0. 8!... .. .001 .008... ..0. 8:80 ..0. 8:80 0....0.00..-0Z .0083:
0.3.2 0 .80 2 ms... .... s. 08... .... 0.3 n... .5
U0...

 

~a...0...0..0u 0.00.053

 

3.0.0.00 00000.... .0. 0.0.00.0 ..0..... 0:0 o...0.00..-+0z .00..

00000.0 80.008800930080... .0 0000090 0000000.... :0. .3 008.0". 0.2.00.0 N 0.00...

73

Table 3 Homoionic Organohecmrites as Phase Transfer Catalysts for
the Displacement Reaction of Alkylbromide with Cyanide

 

 

Sample d001, A Triphase
Onium Ion Number?! Air-dried kobs. hrlb
[C6115CHzNMe3]+ ISAA 14.7 0.006
15AM 14.7 0.006
(0.005)§
[C6H5CHzP(C6H5)3]+ 16AA 18.4 0.012
16AM 18.4 0.014
(0.005)
[CH3NC5H4-C5H4NCH312+ 17AA 13.0 0.003
(0.000)
[Bu4N]+ 18AA 14.7 0.074
18AM 14.7 0.067
(0.563)
[Me3NC16H33]+ 19AA 18.0 0.164
19AM 18.0 0.161
(0.073)
[Me3NC14H29]+ ZOAA 17.0 0.142
20AM 17.0 0.122
(0.066)
[C6H5CH2NMe2C 14H291+ 21AA 18.1 0.163
21AM 18.0 0.153
(0.383)
[C6H5CH2NMe2C16H33]+ 22AA 18.3 0.161
22AM 18.3 0.165
(0.369)
[C6H5CH2NMe2C13H37]+ 23AA 18.3 0.164
23AM 18.3 0.162
(0.418)
[M02N(C12st)2]+ 24AA 20.1 0.162
24AM 20.5 0.165
(0.541)
[MeN(C3H17)3]+ 25AA 21.0 0.181
25AM 20.1 0.185
(1.100)
[Bu3PC16H33]+ 26AA 20.1 0.846
26AM 20.5 0 860

(2.200)

 

74

Table 3 continued

Q

IO

The description AA indicates that the clay was synthesized by ion exchange
of sodium hectorite in aqueous medium. The designation AM indicates that
the organoclay was prepared in aqueous methanol. In both types of synthesis
2 meq. of onium ion was used per meq.of clay and the organoclay was washed
free of excess onium ion.

The triphase kobs values are for the conversion of pentylbromide to
pentylcyanide at 90°C under the following conditions: 2.0 mmole
pentylbromide in 6.0 ml toluene, 20 mole potassium cyanide in 3 ml water,
0.073 meq. organoclay.

Values in parenthesis are kobs values determined under equivalent biphase
conditions, wherein an equivalent amount of onium ion

was present as a soluble bromide or chloride salt.

75

organoclay with onium cation containing short alkyl chain (samples 15AA through
16AA) do not have this ability. These results indicated that molecular structure of the
onium ions inside the gallery affect the ability of the organoclay to serve as an emulsion
former and an effective catalyst. The emulsion forming property allows the reagents to
be brought together in sufficient concentration by stirring and thereby attain conveniently
rapid reaction rates. This could explain why the key to efficient phase transfer catalytic
activity by an organoclay is the ability of the clay to form an emulsion containing the
clay, the organic phase and the aqueous phase.
3. The Dependence of Catalytic Reactivity on the Molecular

Structure of the Organic Substrates

Other parameters that controlled the efficiency of this triphase systems were also
investigated. The results in Table 4 show that organohectorites were useful catalysts for
the chemical conversion of other alkylbromides to alkylcyanides. Increasing the
alkybromide chain length from five to nine or twelve carbon atoms slightly slowed but
did not dramatically alter the reaction rates. These results are in accord with the
hypothesis that the crucial requirement for an effective triphase catalysis is the formation
of an emulsion. Since the length of alkyl chain of the organic substrates does not
influence the conformation of the colloid emulsion, it will not affect substantially the
catalytic reactivity. The slight differences in kobs values for the C5H113r, C9H193r
and C12H258r substrates are due to the nature of organic substrates (Table 4).
4. The Dependence of Catalytic Reactivity on the Concentration

of Substrates and Catalysts

The data in Tables 5 and 6 as well as in Figures 23 and 24 illustrate that the
pseudo first-order rate constants for the organoclay catalysts were linearly dependent on
the concentration of potassium cyanide and organoclay. It is too early to derive a

reaction mechanism on organoclay catalysts. However, future studies of the dependence

76

of the reaction rate on the concentration of organic substrate will help in understanding
whether the reaction occurs at a aqueous-clay interface or at a organic-clay interface.
5. The Dependence of Catalytic Reactivity on the Layer

Charge of Clay Host

The effects of clay layer charge on the catalytic efficiency of organoclay were
intensively studied. Three clays of different layer charge densities were examined :
Laponite, and a synthetic hectorite with a charge density of about 0.4 e' per 020(0H)4
unit and a cation exchange capacity of about 55 meq. per 100 g of air dried clay; a natural
hectorite (California) with a charge density of about 0.6 e' per 020(OH,F)4 unit and a
cation exchange capacity of about 73 meq. per 100 g of air dried clay; a synthetic
fluorohectorite with about 1.8 e- per 020F4 unit and a cation exchange capacity of about
122 meq. per 100 g of air dried clay. The kobs values of the homoionic
[C16H33NMe3]+, [C16Iil33PBu3]+ and [Bu4N]+ exchange forms for the pentylbromide
to pentylcyanide conversion show that catalytic activity was lowest for Laponite, but the
hectorite and fluorohectorite supported catalysts were highly efficient. The kobs value of
[C16H33NMe3]+-hecton'te is 15 times as high as kobs of [C16H33NMe3]+-Laponite. In
the [C16H33PBu3]+ system, a similar result was obtained, the kobs value of hectorite
being 10 time as high as kobs of Laponite. But changing the layer charge density from
hectorite to F-hectorite did not affect the reaction rate dramatically in both clay-
supported [C16H33NMe3]+ and [C16H33PBu3]+ systems (Table 7).

The low (100] for [C15H33NMe3]+-Laponite and [C16H33PBu3]+-Laponite
indicated that the onium ion is oriented with the long hydrocarbon chain essentially
parallel to the silicate surface. In [C16H33NMe3]+-hectorite, with d001 = 18.0 A the
chains are inclined with regand to the layers. The [C16H33NMe3]+ in F-hectorite forms
a lipid-like bilayer, as indicated by d001 of 28 A. These results, along with the catalytic
activity data discussed eariler, indicate that the catalytic activities of organoclays depend

nonlinearly on the orientation and loading of the onium cation inside the gallery. The

77

Table 4 The Dependence of kobs Values on Alkyl Chain
Length for Conversion of Alkylbromides to Cyanidea

 

 

Organoclay Alkylbromide

Catalyst C5H1 lBr C9I-1193r C12H253r
[MeN(C3H17)3]+- 0.140 0.123 0.165
hectorite
[Bu3PC15H33]+- 0.575 0.458 0.378
hectorite
[Me3NC16H33]+- 0.129 0.081 0.057
hectorite
[Me3NC14H29]+- 0.1 15 0.095 0.066
hectorite
[Me2N(C12H25)2] + 0.127 0.075 0.059
hectorite

 

3 Reaction conditions: 2.0 mmole RBr in 6 ml toluene; 20.0 mmole
KCN in 3 ml water; 0.10 g homoionic organoclay; 900C.

78

Table 5 Dependence of k 5 Values on Potassium Cyanide Concentration
for Conversion Ofl’entylbromide to Pentylcyanide;

 

 

Concentration of KCN kobs. hr-1
moles/liter

1.67 0.146

3.33 0.278

5.00 0.423

6.67 0.575

 

a Reaction conditions: 2.0 mmole pentylbromide in 6.0 ml
toluene; 3.0 ml potassium cyanide solution: 0.1 g homoionic
[Bu3PC16H33]+-hectorite; 900C.

79

Figure 23. Dependence of k bs values on potassium cyanide
concentration for te conversion of pentylbromide to
pentylcyanide catalyzed by [C16H33PBu3]+-hectorite.

80

—f—

 

 

0.0

rad

1.0

 

 

wd

( L .41”) sqox

81

Table 6 Dependence of k 5 Values on Organoclay Concentration
for Conversion 0? entylbromide to Pentylcyanide;

 

[Bu3PC16H33]+-Hectoriteb kobs. ill-1
in Suspension, gms.

 

0.025 0.130
0.050 0.303
0.075 0.476
0.100 0.575
0.125 0.746
0.150 0.891
0.175 1.036

 

a Reaction conditions: 2.0 mmole pentylbromide in 6.0 ml
toluene; 20.0 mmole potassium cyanide in 3.0 ml water; 900C.
b Fully exchanged homoionic organoclay.

82

Figure 24. Dependence of kobs values on organoclay concentration for
conversion of pentylbromide to pentylcyanide catalyzed by
[C16H33PBu3]+—hectorite.

83

0N0

0P0
_

b

NCO
_

b

mod
0

b

A63 Becacczlenxfoanza

cV0.0
_

00.0

 

 

 

(L—Jq) sqox

84

cation orientation determined the ability of the clay to form stable emulsion. A similar
relationship between the d001, kobs. and the layer charge density of the clay host was
observed for both the clay-supported [C16H33PBu3]+ and clay-supported
[C16H33NMe3]+ systems.

Hence, a given onium ion with a long hydrocarbon chain, and a clay host with
sufficient layer charge to cause inclination of the alkyl chains relative to the clay layer, is
preferred. The charge density needed to cause inclination of the onium ion chains will
depend on the size of the onium ion, but a value near 0.6 e' per 020(OH,F)4 unit is
typical.

In the clay-supported [Bu4N]+ systems, changing the layer charge density of the
clay support from laponite to hectorite does not alter d001 dramatically. Since [Bu4N]+
has four equivalent alkyl chains, changing the orientation of [Bu4N]+ ion in the
interlayers of clay does not alter d001 significantly. Yet, the kobs value for hectorite was
4.35 times as high as that for laponite. Thus, higher clay charge densities increase the
loading of onium cation and enhance b0th the active sites and the organophilic character
of the organoclay and thereby improve the catalytic activity. However, the second factor
is not expressive in the clay-supported [Bu4N]+ system, Therefore, poor catalytic
activity was observed in this system even with a catalyst of hectorite exchange form.

6. The Dependence of Catalytic Reactivity on the Polarity

of Organic Solvent

Phase transfer catalysis, in general, involves a formation of an ion pair and the
transfer of this ion pair from its "normal" phase into the second phase. Therefore, one
can expect that the physical and chemical properties of this ion pair will affect the
reactivity of phase transfer catalysis. Although little systematic information is available
in biphase systems, it is known that the interactions with solvent will strongly influences

the behavior of ion pairs.

85

$300530 .008 2.0.0
£033 _8 m 3 03:98 833.300 0.088 0.0m ”0:030. _8 0 3 038051800 3088 0d
”0:030:00 02:38 w330=8 05 000:: 0000 3 035.8380: 9 038053800

.0 :380800 00.. 00m: 0:0 00.0063 :3 83:0 05 33 0082008 .33 0003 93—0 =< a

 

- - «80 S; to: 0.: +2300
M: 2 3a 033 :8 $06 0: memfioamaa
83 is. 33 S: :00 0.: memsozmcé
.39. < .58 £9. < .88 39. < .88 :3 52:0
:0 0e 8:832 3e 0.0 832cm :3 0c 8<8enn
0890030 080.00: 03:83

 

doESiBbEm 9 038003.950
00 :380800 .50 3.0: .35 05 :0 0030> m 0x 00 00:00:09.9 h 030,—.

86

Table 8 Dependence of kobs Values on the Polarity of Organic
Solvent for Conversion of Pentylbromide to Pentylcyanide?!

 

 

Organic

Solvent kobs. hr-1
Chlorobenzene 0.254
Toluene 0.575
Decane 0.950

 

a Reaction conditions: 2.0 mmole pentyl bromide in 6 ml toluene;
20.0 mmole potassium cyanide in 3 ml water; 0.10 g [Bu3PC16H33]+-
hectorite; 900C.

87

Three groups of solvents have been classified in this respect : 1) Polar protic
solvents readily solvate both anions and cations and give a high degree of dissociation of
ion pairs. 2) Polar aprotic solvents readily solvate cations but not anion. Ion pairs are
highly dissociated in such solvents. 3) Nonpolar aprotic solvents exhibit good
solubilities toward onium salts but negligible solubility of inorganic salts . In these
solvents the dominant species are ion pairs and the interaction of ion pairs and solvent is
weak.

In PT C reactions it has been found that nonpolar and dipolar aprotic solvents
function well. In general, reactions are faster in the solvents of greater dielectric
constant.

In polymer-based triphase catalyst systems the nature of the organic solvent will
affect the catalytic activity for different reasons. Regen has proposed that the organic
solvent can determine the absorption of reactant on the polymer and control the extent of
swelling, which in turn will detemrine the number of active sites available for catalysis,
and establish the nature of the microenvironment at the active site, thus affecting the free
energy of activation. In the reaction of an alkylbromide with aqueous sodium cyanide
catalyzed by polystyrene-bound phase transfer catalysts, Regen’s work has shown a
modest dependence of rate on the type of organic solvent used (89), and Ford has
demonstrated a reaction rate decreasing with solvent in the order Chlorobenzene > toluene
> decane over wide ranges of particle sizes and polymer cross-linking (95).

An analogous reaction catalyzed by the hectorite-supported [C16H33PBu3]+
showed the opposite dependence of catalytic reactivity on the polarity of solvent (Table
8). The pseudo first rate constant increased as the polarity of the solvent decreased
(Chlorobenzene < toluene < decane). By using the reaction model shown in Figure 22,
we can predict that the kinetics of bromide displacement by cyanide occurring in
organoclay systems are determined partially by the hydrophobic interactions between the

emulsion phase and the organic substrates (alkylbromide), and partially by the

88

electrostatic interactions between the the emulsion phase and inorganic anion (cyanide
anion). Increasing the polarity of organic solvent utilized will increase the interaction
between the organic solvent and organic substrates and consequently weaken the
interactions between the emulsion phase and the organic substrates. This will decrease
the partition of the organic substrates in the reactive center and decrease the catalytic
reacrivity.
7. The Mechanism of Organoclay in Alkylbromide

Displacement by Cyanide Ion

On the basis of the investigations discussed above, the organoclay catalysis
mechanism for alkylbromide displacement can be summarized as follows. The reaction
mixtures formed an oil-in water type emulsion in which the organoclay plays an essential
role in stabilizing the emulsion. The ability of organoclay to serve as an emulsion former
of reaction mixtures is controlled by three factors : the loading of onium ion, the
orientation of the onium cation inside the gallery (both are affected by the preparation
method and layer charge of the clay host) and the molecular structure of the intercalated
onium cation. The fundamental kinetic steps of the organoclay systems for the cyanide
displacement reaction are : i) the alkybromide are attracted to the alkyl chain of catalysts
by hydrophobic interaction, and the CN' are attracted to the polar end of catalysts by
electrostatic interactions; ii) displacement reaction occur in the emulsion phase; iii) the
products, alkylcyanide and Br- are transferred from the emulsion phase back to the
organic phase and aqueous phase respectively (Figure 25).
C. Organic Synthesis Catalyzed by Organoclay

In the previous studies we have demonstrated the feasibility of triphase catalysis
for the attack of cyanide ion on alkylbromides catalyzed by organoclay. In addition to the
cyanation reactions, we now demonstrate that organoclays can be applied to a variety of
useful synthetic transformations, including : 1) ether synthesis, 2) oxidation of alcohols,

3) synthesis of thiocyanates and sulfides, 4) C-alkylation of nitriles, 5) dehalogenation of

89

Figure 25. The fundamental kinetic steps of the organoclay in the
alkylbromide displacement by cyanide ion : i) the organic
substrates are attracted to the alkyl chain of catalysts by
hydrophobic interaction and the inorganic anions are
attracted to the polar end of catalysts by electrostatic
interactions. ii) displacement reaction occur in the emulsion
phase. iii) the products are transferred from the emulsion
phase back to the organic phase or aqueous phase.

zzzzzz

0000000000000

91

vic-dibromides, and 6) halogen exchange. Analogous applications of other triphase
catalysis systems have been surveyed by Dehmlow (34). In the following examples
[MeN(C8H17)]3+-hectorite (25AA) and [Bu3PC16H33]+-hectorite (26AA) were utilized
as catalysts.

The X-ray d001 values of the recovered catalysts used in the above reactions
showed that the catalysts retained their initial d-spacing after the reactions. This
indicates that the organoclays are very stable and do not lose their functionization under
the reaction conditions. The slight difference in X-ray d001 values between the‘original
catalysts and recovered catalysts are probably due to the adsorption of organic species
from the reaction mixture. The products were identified by comparing their 1H NMR
spectrum and IR spectra with those for authentic samples (Table 16) or their GLC spectra
with those of Standard samples.

1. Synthesis of aromatic ethers from phenol

Conventional methods for the preparation of alkyl and aryl ethers are many in
number. However, considerable effort is still being expended in developing new and
more convenient procedures. Organoclays were found to be useful triphase catalysts in
the synthesis of ethers. A phenoxide ion generated by treatment of phenol with aqueous
sodium hydroxide (2.5 M), was reacted with n-pentylbromide at 900C. The reactions
were catalyzed by organoclays 25AA and 26AA (Table 9). Phenyl l-pentylether was
produced in 83% yield within 1.5 and 2 h respectively (Table 9). The molar ratio of
nucleophile, pentylbromide, and catalyst used was 2/1/0.01. In this reaction, unlike the
previous triphase reaction, catalyst 25 AA exhibited better catalytic reactivity than 26AA.
Reeves has reported a similar reaction catalyzed by a polymer-supported phase transfer
catalyst that gave 81% conversion in 1 hr at 1100C and the molar ratio of nucleophile,
pentylbromide and catalyst used was 3/1/0.01 (120). Since the reaction conditions were

not identical, it is hard to compare the efficiency of those two catalyst systems.

92

1. Ether Synthesis

 

2.5 M NaOH
05H11Br + Q—OH ’ Q—O— 05”"

90°

2. Oxidation of Alcohol

H

107 NaOCL
Q—w °
50°

3. Synthesis of Thiocyanates and Sulfides

 

90°

90°

93

4. C-Alkylation at Activated CH-Bonds

50%NaOH f"
50 -

 

5. Dehalogenation of vic-Dihalide

 

Brl-l H

l | Mel + Nazszo3 l
©-°-°- - Q-c-‘°-©

I I . l

H Br 9° H

6. Halogen Exchange

RBr + NaCl ——"’ RC1 + NaBr
90°

94

However, in other studies of similar reaction conditions, the organoclay exhibit a higher
catalytic activity than polymer—supported phase transfer catalysts.
2. Oxidation of Alcohols

Reaction of benzyl alcohol dissolved in toluene with 10% aqueous sodium
hypochlorite in the presence of catalysts 25AA or 26AA at 500C gave benzaldehyde in
83.2% and in 98.4% yield within 10.0 h (Table 10). Further oxidation to benzyl acid
occurred for a longer reaction timer. Regen has attempted a similar reaction catalyzed by
a polymer-supported phase transfer catalysts but it afforded only 51% conversion after 50
h at 500C (86). These results demonstrate that for the oxidation of alcohols, a higher
catalytic reacrivity was found tor the organoclay than for the polymer-supported phase
transfer catalyst.
3. Synthesis of alkyl thiocyanate

The reaction between aqueous sodium thiocyanate solution and n-pentylbromide
was conducted at 900C with organoclay as the triphase catalyst. With a 2/l/0.01 molar .
ratio of thiocyanate, n-pentylbromide and catalyst used, n-pentylthiocyanate was
obtained in 99% and 95% chemical yield after reaction time of 1.5 h and 0.5 h in the
presence of organoclay 25AA and 26AA, respectively (Table 11). By using a polymer-
supported catalyst, Reeves carried out the same reaction under an analogous reaction
condition except at a higher reaction temperature (1100C). He observed a 94% chemical
yield of n-pentylthiocyanate after 2 h (120). This example shows that an organoclay
exhibits better catalytic properties than a polymer-supported phase transfer catalysts.
4. Synthesis of sulfide

The conversions of n-pentyl bromide to n-dipentyl sulfide were catalyzed by
organoclay 25AA or 26AA at 900C. The chemical yields obtained for the two catalysts
were 91% and 97%, respectively after a reaction time of 0.5 h (Table 12). Reeve used
polymer as support in preparation of his triphase catalysts (polystyrene supported-
(CH3)3-PBu-3+). A similar alkylsulfide synthesis with a 1.2/1/0.01 molar ratio of sulfide,

9S

 

 

Table 9 Synthesis of Phenyl n-pentyl ether9
Catalyst Time, hr Yield,% doo1,Ah
BlankQ 1.0 38.5 -
[McN(C8H17)3]+- 1.5 83.0 21.0
hectorite
[Bu3PCl6H33]+ 2.0 83.0 22.9
hectorite

 

a Reaction conditions: 5.0 mmole n-pentylbromide; 10.0 mmole phenol and
6.0 ml of 2.5 M sodium hydroxide solution; no organic solvent is used;
0.05 mole homoionic organoclay; 900C.

X-ray d001 spacing for recovered catalyst.

No homoionic organoclay was used in this blank run.

1010"

96

Table 10 Oxidation of Benzyl Alcoholfi

 

 

Catalyst Time, hr Yield,% d001,/XL
Blanks 10 10.7 -
[MeN(C3H17)3]+- 10 83.2 22.5
hectorite
[Bu3PC16H33]+ 10 98.4 22.5
hectorite

 

Reaction conditions: 2 mmole benzyl alcohol in 3 ml toluene; 5 ml
10% sodium hypochlorite; 0.05 mmole homoionic organoclay; 500C.
X-ray d001 spacing for recovery catalyst.

No homoionic organoclay was used in this blank run.

IOO’ I”

97

 

 

 

Table 11 Synthesis of n-Pentyl Thiocyanateg
Catalyst Time, hr Yield,% d001,Ab
BlankQ 1.5 28.7 -
[MeN(C3H17)3]+- 1.5 99.0 19.2
hectorite
[Bu3PC16H33]+ 0.5 95.0 19.0
hectorite
a Reaction conditions: 10.0 mmole sodium thiocyanate in 4 ml water; 5.0

mmole n-pentyl bromide; no organic solvent is used ; 0.05 mole homoionic
organoclay; 900C.

X-ray d001 spacing for recovered catalyst.

No homoionic organoclay was used in this blank run.

lOlO‘

98

Table 12 Synthesis of n-Dipentyl Sulfideg

 

 

Catalyst . Time, hr Yield,% d001,A.b
BlankQ 1.0 20.0 -
[MeN(C3H17)3]+- 0.5 91.0 21.0
hectorite
[Bu3PC16H33]+ 0.5 97.0 23.2
hectorite

 

a Reaction conditions: 6.0 mmole sodium sulfide in 3.0 ml water;

5.0 mmole n-pentylbromide; no organic solvent is used; 0.05 mole
homoionic organoclay; 900C.

X-ray d001 spacing for recovered catalyst.

No homoionic organoclay was used in this blank run.

10 IO‘

99

n-pentylbromide and catalyst was undertaken by Reeve at 110°C. He observed a 98%
chemical yield after a reaction time of 1.5 h (120). The reaction rates of organoclays are
three time as great as the rate observed for a polymer-supported phase transfer catalyst
when the reaction is run of the same temperature. Organoclays proved to be highly
efficient catalysts in the application of sulfide synthesis.

5. C-alkylation of nitriles

The alkylation of phenylacetonitrile with n-pentylbromide was carried out under
triphase system with 50% sodium hydroxide aqueous solution at 500C. The molar ratio
of phenylacetonitrile, n-pentylbromide and catalyst was 1/ 1/0.01. After 6 h reaction time
a 85% monalkylation was obtained when it catalyzed by 25AA while a 82% chemical
yield was received after 2 h when it catalyzed by 26AA (Table 13). Only monalkylation
was obtained in both reactions. Organoclay 25AA inherits a lower catalytic activity than
26AA as usual.

Dou attempted analogous reactions under both biphase and triphase condition by
using tributyhexadecyl phosphonium bromide and the corresponding polymer-supported
cation as catalysts (142). Under biphase condition, 88% monoalkylation and 9%
dialkylation (in percent for 100% of substrate) was achieved after 10 h at 700C with a
1/ 1/0.01 molar ratio of phenylacetonitrile, n-pentylbromide and catalyst. Increasing the
amount of catalyst by altering the molar ratio to l/ 1/0.1, gave 70% monalkylation and
13% dialkylation after reaction time of 5 h under the analogous conditions. Triphase
reaction conditions gave a best overall yield, up to 72%, and 4.5% dialkylation at 700C
for 10 h reaction time. Comparisons of the catalytic properties of [Bu3PC16H33]+-
hectorite (26AA), polymer supported [Bu3PC16H33]+ and Bu3PC16H33Br indicated
that the organoclays are not only better catalysts than the corresponding polymer
supported catalysts but sometimes they exhibit higher catalytic reactivities and

specificities than the analogous biphase catalysts.

100

6. Dehalogenation of vic-dibromides

Dehalogenation of meso-1,2-dibromo-1,2diphenylethane to stilbene in toluene
was canied out through the use of sodium thiosulfate and sodium iodide. When the
reaction was catalyzed by organoclays 25AA or 26AA, completely stereospecific
conversion to trans-stilbene with 95% and 98% yield, respectively, was obtained at 90°C
after 7 h reaction time (Table 14). Under similar reaction conditions Regen observed the
same product in 100% chemical yield after 12 h by utilizing polymer-supported phase
transfer catalysts (86). As expected, organoclays are better catalysts than other triphase
catalysts.

7. Halogen Exchange

The reactions of aqueous sodium chloride and alkybromide in toluene were
catalyzed by [MeN(C8H17)]3+-hectorite (25AA) and [Bu3PC16H33]+-hectorite (26AA)
at 900C. Table 15 illustrates the conversions for a series of alkybromides to the
corresponding alkylchlorides. The reaction rates were not altered drastically by
increasing the hydrocarbon chain length of the alkylbrornides. These reactions were
limited by the thermodynamic equilibrium values at 3 : 10 for a Br- : Cl- ratio.

By using excess sodium chloride, Regen was able to obtain a modest reaction rate
when the chloride-bromide exchange reaction was catalyzed by polymer-CH2-Bu3P+ at
elevated temperature, 110°C (86, 95). We can expect our reaction rates to increase more
than 11 times if we use an analogous concentration of sodium chloride.

D. Comparison of the Catalytic Properties of Organoclay

The catalytic properties of a few commercial organoclays were studied in
comparison with that of our organoclay (Table 17). In the cyanation reaction organoclay,
Benton 34, exhibited no catalytic activity and gave 0% chemical yield after 24 h reaction
time. Under analogous reaction conditions organoclay ECCT 40 , ECCT AF and ECCT
PS showed modest catalytic activity and received a similar result of 73% chemical

conversion within 8 h. These results, in comparison with our previous work listed in

101

Table 13 C-Alkylation of N itrilesa

 

 

Catalyst Time, hr Yield,% acclaim
Blankfl 6.0 3.5
[MeN(C3H17)3]+- 6.0 85.8 21.5 ‘
hectorite
[Bu3PC16H33]+ 2.0 82.0 21.9
hectorite

 

a Reaction conditions: 5.0 mmole n-pentylbromide; 5.0 mmole benzylcyanide;
2.0 ml of 50% sodium hydroxide solution; no organic solvent is used;

0.05 mmole homoionic organoclay; 500C.

X-ray d001 spacing for recovered catalyst.

No homoionic organoclay was used in this blank run.

1010‘

102

 

 

Table 14 Dehologenation of vic-Dibromidesfi
Catalyst Time, hr Yield,% doo1,A!2
Blankfi 21.0 0.0 -
[MeN(C3H17)3]+- 7.0 95.0 22.5
hectorite
[Bu3PC16H33]+ 7 .0 98.0 20.0
hectorite

 

a Reaction conditions: 1.0 mmole meso- 1,2-dibromo—1,2 diphenylethane in
2.0 ml toluene, 0.246 mmole sodium iodide; 32.0 mmole sodium thiosulfate
in 2.0 ml water; 0.05 mmole homoionic organoclay; 90°C.

1; X-ray d001 spacing for recovered catalyst.

52 No homoionic organoclay was used in this blank run

103

Table 15 Synthesis of Alkylchloride from Alkylbromideil

 

 

 

 

 

 

 

 

Catalyst alkylbromide Time, Yield domh
(hr) (%) (A)

Blanle C5H11Br 48.0 0.0 -
[MeN(C3H17)3]+- C5H11Br 78.0 73.4 21.8
hectorite
[Bu3PC16H33]+ C5H1 1Br 48.0 64.5 22.4
hectorite

Blank2§ C9H19Br 48.0 0.0 -
[MeN(C3H17)3]+- C9H198r 54.0 73.5 21.8
hectorite
[Bu3PC15H33]+ C9H19Br 48.0 62.8 22.4
hectorite

Blank3§ C12H258r 48.0 0.0 -
[MeN(C3H17)3]+- Cleszr 54.0 63.3 21.8
hectorite
[Bu3PC15H33]+- C12H258r 48.0 56.4 22.4

hectorite

 

104

Table 15 continued

Reaction conditions: 2.0 mmole alkylbromide in 6.0 ml toluene; 6.67 mole
sodium chloride in 3.0 ml water", 0.05 mmole homoionic organoclay; 900C.
1: X-ray d001 spacing for recovered catalyst.
Q No homoionic organoclay was used in this blank run.

105

 

.8003N .8003.—
.0 800083 J 833.0

m 583.8 .5888 .8888

.3 0N2
.3 v0: .3 0mN~ .3 05m"
.3 $2 .8 mm: .m 003
.m 3% .3 Ram .8 anon 055.8035. 3:08-:

a 8... .. 8e

.. 8e .. m: .. 8w

.... 82 .3 82 .3 82

.e we: a 8.: .... 8N.

.. 22 .8 82 a 8:

.. 82 a 82 .8 8:

a 8: .e 2 8 .... 88
.... 88 .3 88 .... 88 8282 :28

m 000 .m 03.

.3 m; .3 n5 .3 cow

.3 :00— .3 m2: .3 be:
.m 002 .3 33 .3 32

.8 on: .m 002 ...m 002
.m #02 .8 whwm .sm RQN

 

 

9 8% .3 Son .3 38 Sam 5:08-: .08..
QMEZT: #780 > 2ng
039350 05:00... 3300590

3 8:8... c5 .8 an: :22 3 es. 3.5 8285 2 use...

106

 

58:2
Eaamms .Eamcmfi .m 8&2.

Sam was .. Sauna
.888: .683:
.u 588.: .. 588.8

.Eaaov.m .Eqanné
.: 5&8: .. 6888

Own .5 ovn .m ooh

m o2. .m con .5 OS

.m 8o .3 CR: .5 an»;
.8 com" .3 82 .3 8m:
.3 anon .3 89m .3 95m

.m> wave .5. cm. .8 own
.3 59 .3 Sb— .3 num—

m 33 .E 82 .E NOS
.5 cmNN .m nhwm .m> Son
.5 3% .5 08m .8 Neon

E a; .5 8n

.3 2a .3 3: .E 82
am $318 2.2 .5 SN—
.3 mmg .E n52 .m mm:
.m Vnwm .m> Row .5 «man

23.8-85

0:25:30:
_.9:om-~

08:8 3:25

 

3.27::

fl—qu>

0385

 

3.880 2 22¢

107

.8020: m: 8:80.520 03:88:00

38: 3 8:058 3825 :: m: 0028388882 0. 28:3: 02:38 203 :85: .8825
£80 : 0.5 82: wimmpa 0:: Ex .83 388:: 05 838

.3 38:50 203 800% Bow 8:8 5:2 88 80 3%: .3 38:30 203 :80on :0::_0m
8082.88 .3 098:8 0:: 2:23.

8308 3 not: 8: N 88:5 5 03880: 80508 on. 3:808: 3:33 803 30:00.8 25. w

0|

.Dl

388800 2 03:9

108

Table 3, indicated that similar catalytic properties are obtained for the commercial
organoclay of the ECCT series, and our 19AA-25AM organoclays. However,
[Bu3PC15H33]+-hectorite exhibited a reaction rate which is about four times as fast as
that of the organoclay of ECCT series.
E. Comparison of the Catalytic Properties of Some

Organo-Layered Compounds

A series of layered compounds and their intercalation with alkylamonium ions
were synthesized . The six major layered compound are alpha-zirconium phosphate
(Zr(HP04)2), sodium molybdenum bronze (NaxMoO3), sodium titanate (NaTi307),
sodium tintanium sulfides (NaTiSz), Zn-Cr layered double hydroxide (anCr(OH)6) and
layered chloro tin phosphate (SnCl(OH)(HPO4). The intercalated onium ions were
(C12H25)NH(CH3)2+. (C16H33)N(CH3)3+ and (C12H25)2N(CH3)2+. except for the
layered double hydroxide in which case the intercalated ion was dodecylsulfate. The
catalytic properties of organo-layered compounds were investigated for bromide
displacement both by cyanide and chloride. All of the organo—layered compounds in
these studies were either deintercalated or decomposed in the cyanation reactions, as
indicated by the X-ray data of the recovered catalysts. In the chloride displacement of
pentylbromide reaction, only (C12H25)NH(CH3)2+-zirconium phosphate gave a positive
results (Table 18). Emulsion formation was observed in the (C12H25)NH(CH3)2+-
zirconium phosphate system and an analogous chemical conversion, 62.8% yield after 48
h, was observed for organoclay 26AA. The catalytic conversions, observed for
(C12H25)2N(CH3)2+-[Zr2Cr(0H)6]-[C12H25504]. (C12H25)NH(CH3)2+-Ch10r0 tin
phosphate and (C12H25)2N(CH3)2+-sodium tintanium sulfides were due to the de-
intercalation of the onium cations and their subsequent involvement as biphase catalysts,
and can be proved by the continuation of the reaction after removing the solid catalysts.
Although the catalytic reactivities of the organo-layered compounds were disappointing,

these triphase technique might be able to improve by varying the crystallinity of the

109

Table 1? Catalytic Reactivities of Commercial Organoclay in the
Synthesis of n-Pentylcyanide from n-Pentylbromide under
Triphase ReaCtion Conditionsfl

 

 

Catalyst Time, hr Yield,%
Benton 34h 24.0 0.0
ECCI‘ 40!: 8.0 73.0
ECCT AFh 8.0 7 3.0
ECCT PSD 8.0 72.0
[MeN(C3H17)3]+- 8.0 77.0
hectorite
[Bu3PC16H33]+- 3.5 95.0
hectorite

 

a Reaction conditions: 2.0 mmole n-pentylbromide in 6.0 ml toluene; 20.0
mmole sodium cyanide in 3.0 ml water; 0.13 g of organoclay; 900C.
Benton 24 was donated by Baroid Co. and ECCT organoclay series were obtained
from English China Clay Co.

110

 

AVOEEOXUS

 

 

 

3: 03:8: 2 : o3 IBEUVZQENGV
302032

0: 03:3. od oém +NAm=UVZAnNm§UV
8°25

0: 03:; ed oém +mAm5vammm£UV
3.955

8: 03:: 3... 3:. [423823328

538:0":
8:36: 0:53: $.20; 208$ 933:0

 

magma—0:00

«6.33:0 8:..th :02: 02:.0..£b:0m-: 80:: our—02035:: :0
305:»: 05 :0: «2:09:00 :80»£0::w.5 :0 8230:3— 833“: 3 03a.

.008 "0:509:00 00:93—05:30 w o: .o ".033 :8 Qm E 02:93 833.80:
0:088 36 ”0:020. :8 c 5 02805359: 0:088 QN 600.: 0:03 8:030: $32.0: 0.5. w

 

111

 

 

53.2
9. 03% o: 0.3 IRRBVZQNINGV
$52
2. 03925 3:. 0% 83523920:
8 032,25 0.: 3m .vomnmmfiofifioromé
.vommmmfiufifiorumé
2. 03.28: on: gum Ilkamovzfimmfiuv
con—3:0":
83:5 0:330 $.20; 2.06: 9336

 

3.5.8 E 2%...

112

layered host compounds and by altering the molecular structure of the intercalated onium
ion.
F. Preparation of Clay-Supported Chiral Catalysts

Asymmetric synthesis by using chiral phase transfer catalysts or polymer-
supported chiral phase transfer catalysts has been a subject of interest to several authors
in the last few years. Although the optical purity of the resulting products is low, and
few reaction mechanism have been studied, they are important as an imaginative new
series of catalysts.

In our previous studies of clay-supported phase transfer catalysts we successfully
have translated the solution reactions into triphase systems. With thisbackground, we
attempt to develop a clay-supported chiral phase transfer catalysis. The intercalation of
(-) N-dodecyl-N-methyl ephedrinium and (-) N-benzquuininium on hectorite or
flurohectorite was achieved following an analogous preparation procedure as for the
clay-supported phase transfer catalysts reported earlier. Table 19 illustrates that the d-
spacing of the clay supported (-) N -dodecyl N -methyl ephedrinium increases from 18.57
A to 25.80 A when the layer charge density of clay host increase from 0.6 e' per O4[OH,
F14 (hectorite) to 1.8 e- per O4F4 (F-hectorite). A similar dependence of d-spacing on
the layer charge density of clay support was observed for the clay-supported (-) N-
benzquuininium. This dependence, as previous discussed, is due to the different
orientations of the chiral cation on the clay host of different layer charge density. Cation
orientation appears to be a determinative factor on the efficiency and Stereoselectivity of
the asymmetric synthesis.

G. The Stereoselectivity and Mechanism of the Asymmetric

Reduction of Ketones Catalyzed by Organoclay

There are few studies on asymmetric borohydride reduction of carbonyl
compounds catalyzed by chiral phase transfer catalysts. Colonna and his co-workers

reported that (-) N-dodecyl N-methylephedrinium bromide and (-) N-benzquuininium

113

Table 19 X-ray Basal Spacings Data of Clay-supported Chiral Catalysts?-

 

 

Samples Number d001, A
(-) N-Dodecyl N-Methyl 131AA 18.57
ephedrinium hectorite
(-) N -Dodecyl N -Methyl F131AA 25.80

ephedrinium F-hectorite

 

(-) N-Benzquuininium 151AA 19.60
hectorite
(-) N-Benzquuininium F151AA 22.84
F-hecton'te

a Clay-supported chiral catalysts were prepared under following condition:

1% aqueous clay solution was stirred vigorously with 0.073 M aqueous
chiral onium salt solution for 24 hours. The products were washed free
of excess onium salt. and collected by centrifugation, and air dried at
room temperature; for l meq of clay, 2 meq of chiral onium ion was used.

114

chloride gave 10.6% and 22% ee, respectively, in the reduction of t-butyl phenyl ketone
under biphase condition (69, 143, 141) (the ee numbers given in the literatures were
13.9% and 28.5% according the maximum value of [aJDzo = 30.0 in acetone, but we
recalculated the ee number assuming the value of [a]D20 = 39.6 in acetone (143)).
However, neither chiral catalyst was able to promote asymmetric induction in the
reaction of ketones with less hindered reactive center such as phenyl n-propanone.

So far, no detailed mechanism of asymmetric borohydride reduction catalyzed by
(-) N-dodecyl N-methylephedrinium bromide and (-) N-benzquuininium chloride has
been proposed. However, most research groups have recognized that in order to obtain a
high optical activity in the borohydride reduction, a tight ion pair between the
borohydride anion and the chiral cation has to form, and the B hydroxy group of the
chiral cation should interact with the ketone by oxygen H-bonding.

Several authors have recognized that the Stereoselectivity of chiral catalysis is
affected by the polarity of the solvent employed, the molecular structure of the chiral
phase transfer catalyst, the molecular structure of the substrate and the conditions of the
reaction (temperature, time and catalyst-substrate molar ratio). We have investigated the
behavior of clay-supported chiral phase transfer catalysts in the asymmetric reduction of
ketones by consideration of similar experimental parameters.

In the following experiments, t-butyl phenyl ketone was synthesized according to
the reported literature. The identification of the t-butyl phenyl ketone and the reaction
products was achieved by comparing their 1H NMR spectra and IR spectra with those of
authentic samples (Table 20). The enantiomeric excess of products were determined by
1H NMR in the presence of Eu(hfc)3 as a chiral shift reagent (Figure 26). The non-
catalyzed reactions run under analogous conditions gave 11% chemical yield after 48 h
and 75% conversion after 24 h for n-butyl phenyl ketone and
t-butyl phenyl ketone respectively (Table 21 blank 1-2). Other blank reactions run

without ketones exhibited a zero specific rotation after 72 h under similar reaction

115

conditions (Table 21 blank 3-6). These results indicated that the organoclay of this study

are stable under the reaction conditions and the onium cation is not desorbed into

solution.
1. The Dependence of Enantiomeric Excess on the Layer
Charge of Clay Host

In the reduction of n-butyl phenyl ketone, hectorite-supported (-) N-dodecyl N-
methylephedrinium (131AA) afforded a low reaction rate but high optical activity
compared with the corresponding chiral phase transfer catalysts 100% chemical yield
with 799.7% enantiomeric excess was obtained after a reaction time of 24 h (Table 22).
Replacing the hectorite support (sample 131AA) by F-hectorite (sample F131AA)
resulted in enhancing the catalytic reactivity but decreasing the Stereoselectivity of
organoclay, giving a 100% chemical conversion but essentially no optical yield after 16 h
(Table 22).

Similar influences of support on catalytic activity were observed for hectorite and
F-hectorite-supported (-) N-benzquuininium (151AA and F151AA). However, both
151AA and F151AA show no significant Stereoselectivity (0~1.6% and 1.6~5.0% ee‘
respectively) (Table 22). When the layer charge densities of the clay host are increased,
the active sites and organophilic characters of the organoclay are enhanced. This
enhancement leads to immovement of the catalytic activity of the organoclay.

The predominant enantiomer for the products had R configurations when the
reactions were catalyzed by a hectorite-support chiral catalysts. In contrast, F-hectorite
supported chiral catalysts favored the S isomer. This effect was seen clearly for low
temperature reactions (Table 24). It is evident that the clay host plays an important role
in asymmetric borohydride reduction. The important energy difference between hectorite
and F-hectorite may express themselves in the "best fits" of the transition states. Since
the hydroxy-group and reactive cation center of the catalysts are involved in the

transition state of reaction, their positions and orientations relative to clay support will

116

was... .3 23:8. 350.... S. .... 05.3»...08050. 0. 050.0. 35808 803 3...... 1.0.52.0
......00 .002 ES . .c was... .3 3.5.30 803 0.500% aces—em

.8038 0.5%.... 0... ..o 5.8.59.5 .3 3.00:8 0.83 0.8300...— 0.5.

08...... 80:08 .3 BE. 9... 0:05.00 5.3 03.... 300...... 0... 89¢ 3.00.9.0 0.83 “.803...— 05.

.8038 v... 8.80.820 3.0.5300

0| 'Ul

.91

8.3.3....

.3 3.00:8 ...... 0.83... 8:68 .23 .003. :05 9... £3.38 0.2.3.005 8068 00.883.

.0083 5.3 00:33 803 800.50 0;. es. .050 .33 3.08.5 33 0.5.0.. 3.5.. 3.3-. 2:.

“I

 

8.38.5 .. Same... .... panama
.833. .83.? .. 8&3...

89.2.5 .83 ow...
m Samoa; .m 8.336

Ear—ems .m 8.33..

.m mos. .m 3K. .3 was.
.3 gm .8 82 .E 3.2
.8 men. .3 3m. .8 mm:

.8 em: .5 comm .:0 comm

.m X3 .5 can .3 Omen
.3 Noon .5 exam .3 ween
.... 93

.5 >2. .m 8a .m on:

.0 Na: .8 mum. .8 8m—

.E man. .5. 03: ...... co:

.0. 2.3 .E 82 .0 :2
...m thm .... Cam .8 Gem

99.87..
3.5.. 325. -..

99.00?
380m 125..

0.0.5.3—
3.5.. 19.5..

 

 

322:. 3-80 a 29:8
3500?. 3.5.— 3.5...
c5 .282 .35.. 3.5-. 2.93. 38.. 3....-. 8. sea ..22 m. as 38 85.... cm 2......

Figure 26.

117

The 1H NMR Spectrum of n-butyl phenyl alcohol (0.06 M
in CDC13) in presence of various amount of chemical shift
reagent Eu(hfc)3. The molar ratios of chemical shift reagent
and the alcohol are 0, 0.32, 0.43, 0.52 and 0.87 in (a)-(e),
respectively. -

118

3

3V -

E r

.3

.3

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

119

E i..-

E

.3

 

 

 

E

 

 

 

 

 

 

 

120

.2 83 2.: a 8:68

55 ~208th S: 332 do §-§om a no @8388 9.03 80:88 238% 22.

'Ol

6:653 3525

3 0:83 55 040 3 388% 93 0:98. math: no woman 33 3:83 mo 20% Roman—5

OI

Oaths—85MB 2.8580; 295: Nd
Us“? .8 06 3 35.383 83388 0.088 0 655.3 E o.m ”22.8.80 scanned m
.Uovn v8: 33 zfioocawuo 25582. 2. ”.883 E. ofi 5

 

 

 

 

35283 833.52— oBEE 90:02.3 1: Qm E 0:98— 3088 Wm ”22:38 couoaom w.
06 ed 9Q. - (£3 E mo x55
ed od ad. - <<R _ an .455
ad ed 3:. - <<EE av “Ea—m
ad ad ad. - <52 mm :55
ed oi 3N 3.5-. - a :55
ed q: 3: EB-.. - a x55
u a
8:35 as .22» 2 .08: 956;. .882
ocfioam 32825 5:83. 0:93— .».com 335.5 5383—
m 2.93— .55; 335 Mo couoavom unflinchom mo 32.83. :55 2F 5 32¢.

121

certainly play an important role on the stereochemical course of the asymmetric induction
in the triphase system. Therefore, for a given chiral cation, the ion will orient differently
in the clay host and these differences in orientation will (Table 19) result in different
stereoselectivities.

In presence of hectorite-supported (-) N -dodecyl N-methylephedrinium (131AA),
t-butyl phenyl alcohol was produced within 24 h with no significant optical yield (Table
22). However, utilizing F-hectorite-N-dodecyl N-methylephedrinium (F 131AA),
hectorite-(-) N-benzquuininium (151AA) and F-hectorite-(-) N-benzquuininium
(F151AA) as catalysts, the t-butyl phenyl alcohols were formed with 11.2%, 19.7% and
32.7% ee, respectively. These Optical yields are comparable to the analogous biphase
system catalyzed by (~) N-dodecyl N-methylephedrinium bromide and (-) N-
benzquuininium chloride (10.6% and 22% ee respectively)(144). Comparing these
results with previous data of the reduction of n-butyl phenyl ketone, a opposite
stereoselectivity was observed for a given organoclay. Also for a given intercalated
chiral catalyst, the organoclay with Fohectorite as the support afforded a t-butyl phenyl
ketone with higher optical purity than the organoclay with hectorite as the support.

The generalizations concerning the dependence of the catalytic reactivity and
stereoselectivity of organoclays on the clay host can be summarized as follows : 1) For a
given chiral cation the effectiveness of F-hectorite supported catalysts is higher than that
of hectorite supported catalysts; 2) Hectorite supported catalysts favor R isomers in the
reduction of n-butyl phenyl ketones (Table 22 and 24); 3) F-hectorite supported catalysts
favor of S isomers in the reduction of n-butyl phenyl ketones (Table 22 and 24) and R
isomers in the reduction of t-butyl phenyl ketones (Table 22).

2. The Dependence of Enantiomeric Excess on the Molecular
Structure of Chiral Cations and Organic Substrates
In PT C systems it has been reported by several authors that catalysts derived from

cinchona alkaloids have higher catalytic activity and stereoselectivity than those derived

122

from ephedra alkaloids (63, 64, 143, 144). In the organoclay systems the degree of
stereoselectivity depends both on the molecular structure of chiral cation, and on the clay
support. The general rule about the dependence of the stereoselectivity of the reaction on
the molecular structure of biphase catalysts is not held in the organoclay. For example in
the reduction of n-butyl phenyl ketones, F-hectorite-(-) N-dodecyl N-methylephedrinium
(F131AA) was more efficient than hectorite-(-) N-benzquuininium (151AA) and as
active as F-hectorite-(-) N-benzquuininium (F151AA) (Table 22). Furthermore,
hectorite-supported (-) N-dodecyl N—methylephedrinium (131AA) exhibited a higher
asymmetric induction than hectorite, and F-hectorite-supported (-) N-benzquuininium
cation (151AA and F151AA) (Table 22).

In contrast, for the reduction of t-butyl phenyl ketones, clay supported (-) N-
benzquuininium (151AA and F151AA) have higher efficiency and stereoselectivity than
clay supported (-) N-dodecyl N-methylephedrinium (131AA and F131AA). These
results can be rationalized by the molecular structures of catalysts and organic substrates.
The (-) N-dodecyl N-methylephedn’nium cation and n-butyl phenyl ketones, with linear
alkyl chains fit naturally on top of each Other. (-) N-benzquuininium has been suggested
to prefer a conformation in which the quinoline ring, the C9-O bond, and the n-benzyl
group lie in one plane (Figure 6). This structure does not prefer either ketone. Therefore,
steric effects introduced by the molecular structure of the ketones become important
factors on the stereochemical course of the asymmetric reduction of ketones. Since the t-
butyl group is more hindered than n-butyl group, we can expect a higher optical yield in
the reduction of the t-butyl phenyl ketone catalyzed by (-) N-benzquuininium chloride
under biphase system (131, 132). One must emphasize that, while most chiral catalysts
and polymer-supported chiral catalysts fail to promote the asymmetric reduction of less
hindered ketones, organoclay 131AA is able to achieve about 25.1% optical yield in the
reduction of n-butyl phenyl ketone (Table 24).

123

3. The Dependence of Enantiomeric Excess on the Concentration

of Catalyst and Substrates

For the borohydride reduction of ketones the influences of catalyst concentration
on the enantiomeric excess have not been studied for the biphase catalyst systems.
However, for the reduction of t-butyl phenyl ketone catalyzed by polystyrene-(-) N-
benzquuininium Lamaty reported that the effects of catalyst concentration on the
enantioselectivity depended on the method of mixing the reactants (145). Since Lamaty
did not report the stability of catalysts, we suspect that the variation of specific roration of
products are partially due to decomposition of the catalysts under the reaction conditions
(25 0C and 12 hr). Our studies indicated that for the reduction of n-butyl phenyl ketone
catalyzed by the F-hectorite-(-) N-dodecyl N-methylephedrinium cation (F131AA) the
optical purity of products were the same when 0.2 mmole or 10.0 mmole of catalyst was
used (Table 23). Since the concentration of catalyst will not affect the conformation of
the transition state, increasing the concentration of catalyst will affect the excess
enantiomers of products by decreasing the relative reaction rate of the non-catalyzed
pathway. For the reduction of n-butyl phenyl ketone the non-catalyzed reaction rates are
very low (Table 21) and negligible compared to that of the catalyzed reaction. Therefore,
the effect of catalyst concentration is not significant. However, for the reduction of t-
butyl phenyl ketone the non-catalyzed reaction rate is comparable to the catalyzed
reaction rate (Table 21). We can expect a dependence of catalyst concentration on the
enantioselectivity until the catalyzed reaction rate is high enough that the non-catalyzed
reaction pathway becomes negligible. In the future it would be worthwhile to study the
dependence of enantiomeric excess on the catalyst concentration in the t-butyl phenyl
ketone.

The effects of enantiomeric excess on the concentrations of ketone and
borohydride anion have also been studied (Table 22). Increasing the concentration of the

substrates enhanced the non-catalyzed reactions but it does not change the conformation

124

 

 

 

 

 

 

m 3 :82 x 3 ca 5.5-. 5.5
m 9o 99: «a q... 3 3.5-. <52
m S 2.2 a q... ow 3.5-.. <32
m 3 2x: a as 3 EB-.. <52
m a.» 32 3 ca 3 EB-.. <32
m 3 2x: a 3 3 SB-.. <52
m a
a. .20; a .20; 2 fish 28.8 28a. 9.23. 38:2
.825 3805 8:83. «:5. «8328 oaeam
2:36 35 3.89220
we 3:895 05 E 3:20! 195m ..o actuated untuzneem 03088.34‘ mm 035.

 

a 2...: c8. 2 as 3 3.5-. 5.33

 

125

 

 

 

a 2 Ex: 2 ca 3 33-. <<§m
m 2: 3x: 2 3 ca 3.2: 3:22
a 3.: 2.2 2 3 3 3.5-. <<8E
m 3 c8. 2 as on 3.5... <<§m
m 3 Ex: 2 Q... 3 3.5... 522.2
a a
a .22» a .22» 2 .229 295: 22:8 9.80-2 35:2
32.8 32.5.6 8:802 3:9 moonmeo 295m

 

B=§=8 N3 2%...

126

 

 

 

 

 

 

a 2.: 3x: 3 ed ca .53-. <32
2 a2 .39 3 ed 3 2.52 <32
m 32 Q82 3 3 on 2.5-. <32
m ha 982 E 3 3 33-, <32
2 ed 32 3 ed 3 EB-.. <32
m 2 ix: 3 3 3 EB-.. <32
m 8 3x: 3 3 ca 33-: <32
m 3 Q82 3 3. 3 EB-.. <32
u a.

22. 22> 22. 22> 2 .22: 29:8 28.8 9.20-2 “Benz

3225 32506 8882 «:8. 282.8 225m

 

3.22.8 «a 225

127

 

 

 

 

 

 

 

2 3m 32 2 ca 3 225-. <32m
2 3.; 282 2 ed 3 23..-. <32m
a 5m 32 2 o3 ad .25-. <32".
2 2m ix: 2 3 3 2.3-. <32”.
m an Ex: 2 3 on 2.3-.. 3322
m 3 2.2 2 od 3 2:5-.. <32m
m 3 0.2: 2 3 on 2.3-.. 3322
m Q». 32 2 3 3 EB-.. <32;
u

2. .22» 2. .22» 2 .22... 28:: 28.8 380.2 38:2

22:5 2282.0 8882 .25. 28228 295m

 

255:8 33 2%»

128

..cowao. 5.7. .823
2. 2853. go Seaman on. 5 AN: 2 and 522 E. .3 3:22.22. 83 «.398 utoEoucacm o
.2265... BEBE 2. 2.83.
.23 020 .3 3820.. 203 82.85 6:28. wag... no @023 2.3 .28... .8 22» 32825 n
.Uovxsoocaws 2:20:52 088:. Nd .2225 .2. ed 6:359 ...: QM 3:38:00 .5288 3.5an: a

882.8 33 2%.»

129

 

 

 

Table 23 The Dependence of Excess Eenantiomer on the Concentration
of Clay Supported Chiral Catalysts in Asymmetric Borohydride
Reduction of Ketones;
Sample Amount of Time, Chemical Optical
Number Catalyst hr Yield, % Yield, %
mmole 12 Q
F131AA 0.2 48 100.0 12.1 S
F131AA 10.0 36 100.0 11.4 S
a Remaining reaction conditions: 2.5 mmole n-butyl phenyl ketone

in 3.0 ml benzene; 6 mmole potassium borohydride in 5.0 ml
water; -100C.

12 Chemical yield of alcohol was based on starting ketone. Product was
detected by GLC with decanc as internal standard.

g Enantiomeric excess was determined by 1H NMR (250 MHz) in the presence
of Eu(hfc)3 as chiral shift reagent.

130

of the transition state. Thus, when the non-catalyzed reaction pathways are insignificant,
the concentrations of substrates do not affect the enantiomeric purity of the products.
4. The Dependence of Enantiomeric Excess on the Temperature

For both n-butyl phenyl ketone and t-butyl phenyl ketone reduction the
enantiomeric purity of the corresponding alcohols increased with decreasing the
temperature (Table 24). For F-hecton‘te-(-) N-dodecyl N-methylephedrinium (F131AA)
as catalyst, the reduction of n-butyl phenyl ketone afforded 12.1%, 0.8%, 0%, 0% cc at
the reaction temperatures of ~100C, 40C, 250C and 500C respectively. The reduction of
t-butyl phenyl ketone gave 11.4% and 8.7% cc at ~100C and 40C respectively. For the
reduction of n-butyl phenyl ketone hectorite-(-) N-dodecyl N-methylephedrinium
(131AA) showed a similar dependence and afforded 25.1% and 9.7% cc at -100C and
40C respectively. Temperature can affect the degree of asymmetric induction in two
ways. First, as the temperature increases, it promotes the reaction through the non-
catalyzed pathway, which results in racemic mixtures. At lower reaction temperatures
the reaction rate of the non-catalyzed pathway, which has a higher activation energy, is
not comparable to that of the catalyzed pathway. Therefore, the catalyzed reaction
becomes the major reaction pathway (according to the Arrehenius equation : rate
coefficient k = A exp (-Ea/RT)) . Similarly the small energy difference between
diastereomeric reaction paths will caused greater stereoselectivity at low temperature.

Also, molecular motion increases with temperature and the conformation of the
transition state through the catalyzed pathway will lose its rigidity and decrease the
stereoselectivity. This second effect may not be as drastic for the more hindered t-butyl
group as for the n-butyl group. Thus, in the reduction of t-butyl phenyl ketone, the

temperature effects are higher than those in n-butyl phenyl ketone.

131

5. The Dependence of Enantiomeric Excess on the Polarity

of Organic Solvent

Another important generalization that seems to be emerging in enantioselectivity
concerns the nature of the organic solvent employed. In a biphase catalyst system, more
often than not, the highest inductions are observed with non-polar solvents. Ion pairs
with strong association play a crucial role in the asymmetric induction. Media capable of
hydrogen bonding or solvating chiral ion pairs generally inhibit induction because of a
weakening of the ion pair interaction. This could also explain why in solvents with high
dielectric constant, where the force between two charged species is weak, the
enantiomeric purities are substantially lower than in solvents with low dielectric constant.
Similarly, in clay-supported chiral catalysis one observed the dependence of
stereoselectivity on the polarity of organic solvents employed. In the presence of
benzene, hectorite-H N-dodecyl N-methylephedrinium (131AA) afforded a predominant
enantiomer of R configuration with 9.7% optical yield in the n-butyl phenyl ketone
reduction, whereas in THF, 131AA afforded a predominant enantiomer of opposite
configuration with 8.6% cc (Table 25). The complexity of clay-supported chiral catalysts
and the lack of kinetic data make it difficult to rationalize the results. However, from our
knowledge of previous experiments, the organic solvents can affect the emulsion
formation of reaction mixtures which in turn affect the reaction rate of catalyzed
pathway. When the catalyzed reaction becomes the major reaction pathway we can
expect to obtain a higher degree of enantioselectivity. The organic solvents can also alter
the interaction of the chiral ion pair and influence the asymmetric induction. There is no
generalization of the solvent effects in this system. It is necessary to study each clay-
supported chiral catalyst individually for this subject.
6. Conclusion

Although a great deal of research needs to be done before the mechanism of clay-

supported chiral catalysis can be proposed, it appears worthwhile to summarize the

132

results of the study of ketone reduction : 1) For a given intercalated chiral cation, the
organoclays of hectorite and F-hectorite supports tend to afford predominant enantiomers
with opposite configurations; 2) The concentrations of substrates do not affect the degree
of enantioselectivity; 3) The concentration of hectorite-supported (-) N-dodecyl N-
methylephedrinium (131AA) catalyst affects the reaction rate but not the stereoselectiviy
for the reduction n-butyl phenly ketone. However, this concentration effect of catalyst
should be studied individual for different clay-supported chiral catalysts and organic
substrates. 4) In general, low temperature favors the stereochemical course of
asymmetric ketone reduction. However, the extent of the temperature dependence is
different for various ketones. 5) Changing the solvent can afford products in favor of
opposite isomer. However, the effects of organic solvents are not clear at this point.

It has to be said that the clay-supported chiral catalysts are practically superior to
conventional biphase catalysts. Moreover, for a given chiral catalyst we are able to alter
its optical selectivity by intercalatin g the chiral catalysts on various clay hosts.

H. The Stereoselectivity and Mechanism of Asymmetric

Epoxidation of Chalcones Catalyzed by Organoclays

The epoxide function plays an important role in metabolic processes. It is
surprising therefore that the catalytic synthesis of optically active epoxides leaves much
to be desired. Wynberg has attempted to epoxidize chalcone under the influence of
quinine and ephedrine but the results were disappointing. However, chalcones and
related compounds could be transformed in excellent chemical yields into optically active
epoxides by using quaternary salts derived from quinine as chiral phase transfer catalysts
in biphase systems (63). A limited study and the lack of kinetic data make it difficult to
drive conclusions concerning the role of the catalyst structure and to propose reaction
mechanisms. Nevertheless, Wynberg and Dollin g have stated that the cinchona alkaloids

are by far the better all around catalysts; and that the absolute configuration at C-8-C-9 of

133

 

 

 

 

Table 24 The Dependence of Enantiomeric Excess on Temperature

in Asymmetric Borohydride Reduction of Ketones with

Clay-Supported Chiral Catalystsa
Sample ketone Temp. Time, Chemical Optical
Number R-Group 0C hr Yield, Yield,

%._b %. 2

F131AA n-butyl -10 48.0 100.0 12.1 S
F131AA n-butyl 4 16.0 100.0 0.8 S
F131AA n-butyl 25 8.5 100.0 0.0
F131AA n—butyl 50 5.0 100.0 0.0
F131AA t-butyl - 10 22.5 100.0 11.4
F131AA t-butyl 4 10.0 100.0 8.7
131AA n-butyl -10 72.0 100.0 25.1
131AA n-butyl 4 24.0 100.0 9.7

 

Reaction conditions: 2.5 mmole ketone in 3.0 ml benzene; 6 mole potassium
borohydride in 5.0 ml water“, 0.2 mmole homoionic organoclay.

with decanc as internal standard.

Eu(hfc)3 as chiral shift reagent.

Chemical yield of alcohol was based on starting ketone and detected by GLC
Enantiomeric excess was determined by 1H NMR (250 MHz) in the presence of

134

Table 25 The Dependence of Enantiomeric Excess on the Polarity of
Organic Solvent in Asymmetric Borohydride Reduction of
Ketones with Clay-Supported Chiral Catalystsfl

 

 

Sample Organic Time, Chemical Optical
Number Solvent hr Yield, % Yield,%
12 2
131AA CC14 24.0 100.0 5.4 R
131AA C6H6 24.0 100.0 9.0 R
131AA THE 24.0 100.0 8.6 S

 

a Reaction conditions: 2.5 mmole benzyl n-butyl ketone in 3.0 ml organic
solvent; 6 mmole potassium borohydride in 5.0 ml water; 0.2 mmole homoionic
organoclay;40C. .

Chemical yield of alcohol was based on starting ketone and detected by GLC.
Enantiomeric excess was determined by 1H N MR (250 MHz) in the presence of
Eu(hfc)3 as chiral shift reagent.

1010'

135

the alkaloids govern the absolute configurations of the products. A mechanism, as
discussed in chapter 1, concerning a compact ion pair was presented by Wynberg (63).

Epoxidation of chalcone catalyzed by benzyl quininium chloride affords a 34%
optical yield in the presence of 30% hydrogen peroxide and 10% sodium hydroxide. The
predominant configuration of epoxychalcone is S with an R configuration at the a-carbon
and an 8 configuration at the B-carbon (Figure 27). Kobayashi has utilized a polystyrene
supported quininium salt as a catalyst in chalcone epoxidations, and the results do
parallel those of the analogous non—supported reactions (43).

The phase transfer-mediated asymmetric epoxidation by using clay-supported
ephedrinium salt (131AA) was attempted with little success (T able 26). However, clay-
supported cinchona alkaloids (151AA, F151AA) exhibit a higher stereoselectivity than
analogous non-supported or polymer supported cinchona alkaloids and afforded products
with maximum optical yield, up to 46.7% (Table 29). The blank reactions were carried
out under the conditions either without the chalcone or clay-supported chiral catalysts
(Table 27). No specific rotations was observed by polarimeter when no chalcone was
used. These results indicated that both 151AA and F151AA were stable under the
reaction conditions. If organoclays lost their functionizations or the intercalated cation
decomposed under the reaction conditions the specific rotations of the reaction residence
should be greater than 0. The non-catalyzed reaction rate was very low and non
significant product was observed after 3 days (Table 27).

l. The Dependence of Enantiomeric Excess on the Layer

Charge of Clay Host

According to the previous discussion, the layer charge density of the clay host
affects both the loading and the orientation of onium cation. This, in turn, influences the
catalytic and stereoselective properties of clay supported chiral catalysts. For the
epoxidation of chalcone catalyzed by the F-hectorite supported n-benzyl quininium

(F151AA) the reaction rate was about 5 times as fast as that of the analogous reaction

136

catalyzed by hectorite supported n-benzyl quininium (151AA). Nevertheless, these two
clay-supported chiral catalysts possess a similar enantioselectivity and afforded
predominant enantiomers of opposite configuration. For instance, with F151AA as
catalyst, the reactions afford a 100% chemical yield and 27.9% enantiomeric excess of
epoxychalcone with a predominant isomer of S configuration (Table 28). In contrast, a
predominant R enantiomer was found in the analogous reaction catalyzed by 151AA
(21.0% ee). These results were consistent with the observations in the asymmetric
borohydride reduction. For a given intercalated chiral cation, the F-hectorite support and
hectorite support afforded analogous products with predominant enantiomers of opposite
configuration.

For a preferred conformation of benzyl quininium cation (Figure 6), tight ion
pairing between the chiral cation and the peroxide anion, and hydrogen bonding between
the hydroxyl of the alkaloid and the carbonyl oxygen of the chalcone, suggest the
conformations of transition state shown in Figure 28. The various possible
conformations of transition state introduced by diverse clay hosts have different
activation energies. The various organophilic characteristics of diverse clay hosts also
affect the catalytic activity of the organoclay. These may explain the influence of clay
hosts on the catalytic and enantiomeric properties of clay-supported chiral catalysts.

2. The Dependence of Enantiomeric Excess on the Temperature

Colonna has reported that in the presence of polymer-supported chiral catalysts,
the degree of asymmetric induction in the epoxidation of chalcones decreases as the
temperature increases (146). A‘ similar dependence of stereoselectivity on the
temperature were reported for other asymmetric induction under biphase systems (63,
147). However, in the organoclay catalysis, we discovered, that fOr the chalcone
epoxidation, the enantiomeric purity of the epoxychalcone increased with temperature.
Table 29 illustrates that the reaction catalyzed by F511AA in presence of carbon

tetrachloride afforded 46.7% ee at 250C and 17.0% ee at 40C. Analogous reactions in

137

 

 

Figure 27. Configuration of (-) Epoxychalcone.

138

 

 

Table 26 Dependence of Enantiomeric Excess on the Molecular Structure

of Chiral Catalysts for Asymmetric Epoxidation of Chalcone

with Clay Supported Chiral Catalystsé
Sample Reaction Chemical Optical
Number Time, hr Conversion, % Yield,%

12 9

131AA 102 100.0 0.7 a—S, B—R
151AA 102 100.0 21.0 a—S, B—R

 

a Reaction conditions : 0.48 mmole chalcone in 3 ml benzene; 30%
H202 1.5m] and 12% N aOH 1.5 ml; 250C; 0.2 mmole homoionic organoclay.

b The reaction was monitored by TLC until no trace of the starting reagent
(chalcone) was present.

Q Enantiomeric excess was determined by 1H NMR (250 MHz) in the presence of
Eu(hfc)3 as chiral shift reagent.

139

.. < 8% < 2.5 8.. 8.8.2:

5.3 368223 .3 .252 do hoe—macro; a :0 3.3368 0.83 20226.. 2.28% 05.
.cm 035. E

3.86:. 0:5 .6282 on. .22. 258 8: 2.3 8.60:. .8228. 05 we 8...: OH“. 25.
.003 $285.96 2.5682. 208:. Nd ..E n.—

mOaZ gen. .2... .2. n4 NONE oeom "econ—.3 .8 Gm 6:026:60 23.83.

.003 ”.8 2. 39.2 $3 9... .8 m.—

NONE amen "econ—.3 .5 ca 5 0:835 2688 cad ”2.2.6.50 .8283. m

OI'UI

.Dl

 

 

od - QS. <52". mm 25.5
od - ONE ()2 2 Am 6:85
ad ad o3» - m. 255

u u .2.
.5233— :omm..0>=oU .2 .083. 23:52
056on 32:86 .5263”— .deEU .5203“

 

a 2.8.2.0 .o 8828...". ..o 888.. 28... 2F R 2...»

140

Figure 28. The possible conformation of transition state of the
chalcone epoxidation catalyzed by 151AA

142

.8030.

 

 

 

......m .820 v... £0.53 ..0 00:30... 0... ... G: .2 SN. ”:27. ... .3 00885.00 2.3 3.00.8 0.580.235. M
0:80.... 83 6.50.5.0. 809.0. wig... 0... .0 008. 0.. ....5 Us... .... 029.58 33 80.5.3. 0.... m.
$2008.30 080.080.. 0.088 Nd "U03 ”.8 n. :92
Q0... ...... .8m.. NON: $0.“ “8030.. 0.835 .8 m ... 0.50.20 0.088 5.... . 80.50.50 80.53.. 3.8.080... w.
.... .mé ...... 08. 8. <<.n.
m... ...-.. ...: 08. 8 <32”.
m m

o... .20; .0 80.80800 .... .08.... 508:2
.880 .8825 888.. oasam

8.9.3.0 ......U 0080.53-86

....3 0.50.5.0 .0 8083300.". 08088....< 5.. .8: 8.0 0...
.0 03.2.0 .0»... 0... .5 mmooxm 0.580382... .0 0080.52.00 mu 0...“...

143

the presence of benzene bear 27.9% ee at 25°C and 10.6% ee at 4°C. In contrast
utilizing 151AA as the catalyst, a predominant isomer of opposite configuration was
obtained with 25.3% cc at 250C and 14.2% ee at 40c.

Although increasing the temperature will enhance the reaction through the non-
catalyzed pathway, this is not significant for chalcone epoxidation at the experimental
temperatures used here (Table 27). Figure 29 presents a hypothesis concerning the
dependence of reaction rate on the temperature. For the expoidation catalyzed by
F151AA the formation rate of R isomer is higher than that of S isomer at high
temperature . However, the formation rate of the S isomer does not respond to
temperature as drastically as that of the R isomer. Therefore, as .the temperature
decreases the formation rates of R and S isomers become equal and no enantioselectivity
will be observed. Furthermore at extremely low temperatures one can expect that the S
isomer to become the predominant product. An analogous dependence of optical yield
on the temperature was obeyed for the epoxidation catalyzed by 151AA. The reaction
rate of S isomer instead of the R isomer responds more drastically to temperature change.
Thus, the prevalent enantiomers have an R configuration at high temperature while a
predominant S isomer is expected at low temperature.

3. The Dependence of Enantiomeric Excess on the Polarity

of Organic Solvent

Both Wynberg and Colonna have claimed that the quininium salt catalyzed phase
transfer reaction are subject to strong solvent effects (63, 148). Non-polar aprotic
solvents give higher asymmetric induction than solvents with high dielectric constants
which inhibit the asymmetric induction by weakening the ion pair interaction (63, 148).
However, in the polymer-supported chiral catalyst systems there is no direct correlation
between the dielectric constant of the solvent and the enantiomeric excess of the

epoxychalcone obtained (146). The epoxidation of chalcone catalyzed by F151AA

144

afford 46.7%, 27.9% and 8.2% cc in the presence of carbon tetrachloride, benzene and
THF respectively (Table 30).

While utilizing 151AA as catalySts the degree of stereoselectiviy in the
epoxidation of chalcones was nearly the same in the presence of carbon tetrachloride and
benzene (25.3% and 21.0%). Since CC14 and C6H5 have similar dielectric constant
(2.23 and 2.28 respectively); An analogous solvent effect on the optical activity should
be observed in CCl4 and C6H6, if there is a direct correspondence between the polarity
of solvent and the optical activity of the reaction. It is too early to rationalize the solvent
effects on the stereoselectivity of the organoclay systems. However, according to
previous studies we can expect different organoclays to have varying dependencies of
organic solvent on the enantioselectivity of the epoxidation reaction.

4. The Dependence of Enantiomeric Excess on the Concentration

of Chalcone

Since the concentration of chalcone does not affect the conformation of transition
state of reaction, there is no substantial change of the stereoselectivity of the reaction
when the different concentrations of chalcone are employed (Table 31). This observation
is identical with that of the asymmetric borohydride reduction in the organoclay systems.
5. The Dependence of Enantiomeric Excess on the Volume Ratio

of Aqueous and Organic Phases

Table 31 illustrates the results concerning the dependence of enantiomeric excess
of products on the volume ratio of the aqueous and organic phases. For a constant
concentration of catalyst and substrate, the catalytic reactivity and stereoselctivity of the
reaction decreases as the aqueous volume employed increases. The epoxidation of
chalcone was complete after 44 h and the optical yield was 29.1% when the volume ratio
of aqueous and organic phases equal to 1. It took 64 h and 102 h to complete the
reactions when the volume ratio was increased to 5/3 and 7/3, and the optical yield were

20.8% and 15.4% optical purities, respectively. The volume ratio of aqueous and organic

145

phases is especially important in determining the characteristics of the emulsion for
reaction. This, in turn affects the reaction through the catalyzed pathway and influences
the degree of enantioselectivity.
6. Conclusions

A few results of epoxidation of chalcone catalyzed by organoclay are summarized
as follows : 1) For a given intercalated chiral cation the F-hectorite and hectorite supports
yielded epoxychalcones with predominant enantiomers of opposite configuration. 2) The
concentration of chalcone does not affect the optical purity of product. 3) Over the
experimental temperature range, 250C to 40C, the stereoselectivity of the reaction
increases with temperature. 4) Carbon tetrachloride is thus for the solvent of choice in
the asymmetric epoxidation of chalcone catalyzed by organoclay 151AA or F151AA. 5)
The volume ratio of aqueous and organic phases is especially important in determining a
characteristics of the emulsion of reaction mixtures, which in turn affects the catalyzed

reaction rate and influences the degree of enantioselectivity.

.80w00.

 

 

 

 

 

 

...... .0....0 00 20.5.5 .0 00:05.0 0... ... .0: S. anv 0.22 ... .... 000.8550 003 0000.5 0.580.800... 0
80.0.0 00>. 0.50.0.5. 80w00. 8.0.0.. 0... .0 000.. 0.. .....0 0..... .... 005.808 003 00.500. 0..... m
. 00.008030 005.080.. 0.088 Nd ”.8 n. .0007.
c0N. 0:0 .80. NONE 008 ”80200. 0.8030 .8 m ... 0.50.0..0 0.088 mvd . 800.0000 80.500. 8.0.080... .0
a... .010 $0 0.8. S. :00 m... <<§
.... .010 N... 0.8. 00. 0.00 c <<.0.
01.. ...-.. a... 0.8. cm 0:00 mm <52.
m... ...... 0.0. 0.8. N. 0:00 c <52.
6
M -- ...........................................................................................................................
m... .....e 8.. 0.8. o... 300 n <52...
010.010 ...: 0.8. N. :00 ... <50...
.0. 0
00.0.0; 00 80.05800 ....08.... 80>.0m 00 508:7.
.00..0O 0.0.82.0 80.5000 0.0030 .080 ... 0.080m

 

8....an 80.0
00.500.54.50 ....3 0.50.0..0 .0 00000.50m 0.808803. .
5. 0.805080... 0... .5 mmooxm 0.580.808”. .0 00.50.5000 0N 0.00...

147

Figure 29. The hypothesis of the dependence of the reaction rate on the
temperature A) Epoxidation of chalcone by F151AA B)
Epoxidation of chalcone by 151AA

 

Ink

148

HT

(3)

 

 

 

1/T

(A)

 

 

Ink

 

.4.“

149

.8095.

.....0 .085 00 20.5.5 .0 00:80.0 0.0 0. .0... .2 and M22 .... .3 000.8550 003 0008.0 0.580.885
8000.0 003 5000.000. 80w00. 00.0.0.0 0... .0 000.0 00 ..80 0..... .... 005.808 003 00.500. 0.....

«DID

0.0500030 0.00.0800 0.088 N... .003 ..8 n. $002
002 000 .8n.. NONE 000m .8038 0.0030 .8 m 0. 0000.000 0.08... «0... . 800.008 00.500. 88.080... 0

 

 

 

 

0... .0... 0... 0.8. 8. 0000 <<.0.

0... .0... 0.0. 0.8. 8. 300 <<.0.

0... .00 0.0 0.8. 0. 0.... <<.0..

0... .0... a... 0.8. on 0000 <<.0.0

0... .0-.. ...... 0.8. o. 300 <50...

0 ...

2. .0.0.> .00 80.0.0800 ... .08.... 80>.0m .00802

0.0000 .00.8000 00.5000 0.0030 0.080m
0050.000 .0 00.000505 0.008800... .0. 80>.0m 0.0030

.0 5.8.00 0... 00 0000.5 0.580.885 .0 0000000000 on 0.00...

80000. .....0 .0800 00

 

 

 

 

20.5.5 .0 00500.0 0... 0. A a: .2 03 v 022 .... .... 008.8050 003 0008.0 0.580.805 .0
8000.0 003 80000. 000.00 0... .0 000.0 00 ..80 0..... .3 0058008 003 00.500. 0..... 0
00300500030 0.00.0800 0.088 Nd 500000.. .8 0.... ”0000.050 00.500. 8.8080”. .0.
0... .010 ...0. 0.8. 8. 00.0 0.0 0.0 <<.0..
0.0 .0... 0.0. 0.8. 5 00.0 0.0 0.0 <<.0..
0... .0... .0. 0.8. 3 00.0 0.. 0.. <50...
0... .0-.. 0.0. 0.8. 8. 00.. 0.. 0.. <<.0..
O
b 0... .0-... .0. 0.8. 3. 00.0 0.. 0.. <<.0..
min 5:0 0.8 0.8. ON 3.... 0.. n. <<.n.0
w .0.. a .0.. .8 .8
.05; 00.0.0800 ... .08.... 0.08... 00m. $0.” 50802
.5000 00.8000 00.5000 0000.000 1002 NON: 0.080m

 

000.000 ......0 80800.05 5.3 88.2.0
.0 000000.005 0.008800. .0. 00000 0.0030 000 00000.). .0 000m 080.0>
000 00.0.0085 .0 00000000000 0... 00 0000.5 0.5888005 .0 0000000000 .m 0.00...

151

CHAPTER IV

RECOMMENDATIONS

Although in this study we have successful translated solution reactions into a
triphase organoclay system, there are a few studies worthy of exploring in the future.

Several parameters which control the efficiency of the organoclays in
nucleophilic substitution remain to be studied : 1) the dependence of the catalytic activity
on the swelling properties of the organoclay in various organic solvents. 2) the
dependence of the catalytic properties on the volume ratio of aqueous and organic phases.
Preparation of a new series of organoclays by intercalation of crown ethers or cryptands
in the clay may be worthwhile to attempt. In addition to the reactions that were
investigated in this study, the organoclays can emerge as a broadly useful tools in other
organic synthesis : 1) alkylation and condensation reactions 2) Ylide-mediated reactions
3) miscellansous reactions.

The investigations of organo—layered compounds as triphase catalysts have just
been initiated. The catalytic properties and mechanisms of organo-layered compounds
remain obscure. However, this technique can be understood better by synthesis of
various organo—layered compounds with different crystallinity and molecular structure of
the intercalated onium ion. The mechanisms of catalysis of organo-layered compounds

can be investigated by examining the parameters that control the efficiency of the

152

organoclay catalysts (e.g., the structure of intercalated onium cations, the concentration
of substrates and catalySts. the degree of crystallinity of the layered compounds and the
polarity of organic solvent). Furthermore, the intercalation of chiral catalysts in the
layered compounds perhaps can be developed into other types of triphase chiral catalysts.

It is evident that the clay-supported chiral catalysts are superior to corresponding
chiral catalysts and polymer-supported chiral catalysts. Attempts to prepare a new series
of clay-supported chiral catalysts by intercalating the (+) n-benzyl quinidium cation or
chiral crown ether complexes (125) on the clay is worthwhile. For the borohydride
reduction the mechanism can be understood better by further examinations of the
dependence of catalytic activity and the stereoselectivity of the reaction on 1) the volume
ratio of aqueous and organic phases; 2) the method of mixing the reagents; 3) the alkyl
chain length of ketone; 4) the swelling of clay-supported chiral catalysts in various
organic solvents; and 5) temperature. The epoxidation of chalcones, catalyzed by
organoclays can be expanded into the epoxidation of electron-poor olefins ( e.g.,
chalcones, quinones and cyclohexenones) (68, 69, 77, 78, 81-83). The catalytic activity
and the stereoselectivity of the reaction might be improved by using t-butyl
hydroperoxide or 28% sodium hypochlorite instead of hydrogen peroxide.- Other
parameters that might affect the catalytic activity and the stereoselectivity of the system
are : 1) the method of mixing the reagents; 2) the swelling of clay-supported chiral
catalysts in various organic solvents; 3) the molecular structure of the organic substrate;
and 4) temperature.

In addition to the borohydride reduction and epoxidation of electron-poor olelfins,
several successful application of chiral phase transfer catalysts in asymmetric induction
have been investigated : Michael reactions (34, 63, 73-76), 1,4-thiol and thiolacetate
additions (34, 63, 75), selenophenol addition reaction (34, 63, 151), 2,2-cycloaddition
reaction (34, 64, 76, 150) and 1,2-additions (34, 63, 151). From our previous studies, we

153

can also expect that those reactions may achieved high stereoselectivities by utilizing the

clay-supported chiral catalysts.

>09°>’.°‘.‘"PP°

11.

12.
13.
14.
15.

16.
17.
18.

154

LIST OF REFERENCES

G. Brown, Ed., "X-Ray Identification and Crystal Structure of Clay Minerals",
Mineralogical Society, London, 1961.

G.W. Brindley and G. Brown, Eds, "Crystal Structures of Clay Minerals and
Their X-Ray Identification", Mineralogical Society, London, 1980.

TJ. Pinnavaia, Science, 1983 229, 365.

S.L. Swartzen-Allen and E. Matijec, Chem. Rev., 1974 14, 385.

E.T. Uskova, N .G. Vasilev, and LA. Uskov, Colloid J. USSR, 1968 3_Q, 118.
JD. Bemal, "The Origin of Life", Widenfield and Nicholson, London 1967.
D. Fishman LT. Klug and A. Shani, Synthesis, 1981, 137.

LS. Newton, Speciality Chemicals, 1984, 17.

B.I(.G. Theng, "The Chemistry of Clay—Organic Reactions", Adam I-Iilger,
London 1974.

CM. Starks, J. Am. Chem. Soc., 1971, 93, 195.

(a) CM. Starks and DR. Napier, US. patent, 3992432, 1976; (b) C.M. Starks and
DR. Napier, British patent, 1227144, 1976; (c) C.M. Starks and DR. Napier,
French patent, 1573164 1969; (CI) CM. Starks and DR. Napier, Australian patent,
439286, 1969; (e) C.M. Starks and DR. Napier, Netherlands patent, 6804687,
1968.

CM. Starks and RM. Owens, J. Am. Chem. Soc., 1973 25, 3613.

E. Muller, O.Bayer, and H. Morschel, Germ. Offen1., 268621, 1913.

J. Jarrousse, CR. Acad. Sci. Paris, 1951 232, 1421.

(a) A. T. Babayan, N. Gambaryan, and NP. Gambaryan, Zh, Obshch. Khim.,
1954 M. 1887; (b) A. T. Babayan, N. Gambaryan, and NP. Gambaryan, Chem.
Abstr., 4910879, 1955; (c) A. T. Babayan, N. Gambaryan, and NP. Gambaryan,
Chem. Zentralbl. Sonderb., 1950 SA, 4532.

G. Maerker, J.F. Carmichael, and W. Port, J. Org. Chem, 1961 26, 2681.

DuPont, British Patent 632346, 1949.

P. Edwards, US. Patent 2537981, 1951.

19.
20.
21 .
22.
23.
24.
25.
26.
27.
28.
29.
30.

31.
32.

33.
34.

35.

36.

37.
38.

39.

41.

155

Pest Control, Ltd., British Patent 692774, 1953.

R. Kohler and H. Pietsch, German Patent 944995, 1956.
BB. Copelin and GB. Crane, US. patent 2779781, 1957.
Farbenfabriken Bayer, German patent 959497, 1957.

B. Graham, US. Patent 2866802, 1958.

Gavaert Photo-Produce N.V., Beligian Patent 602793, 1961.
BE. Jennings, British Patent 907647, 1962.

W.S. Port, British Patent 912104, 1962.

RW. Kay, British Patent 916772, 1963.

F. Nerdel, British Patent 1052047, 1966.

BC. Oxenrider and RM. Hetterky, US. Patent 3297634, 1967.

M. Makosza and B. Serafinowa, Rocz. Chem, 1965 32, 1223 and subsequent
papers. .

E.V. Dehmlow, Angew. Chem. Inst. Edu., 1977 _1_6, 493.

CM. Starks and CL. Liotta, "Phase Transfer Catalysis Principles and
Techniques", Academic Press, New York, 1978.

J.E. Gordon R.E. Kutina, J. Am. Chem. Soci., 1977 22, 3903.

E.V. Dehmlow and 8.8. Dehmlow, "Phase Transfer Catalysis", Verlag Chemie,
Basel, 1983.

W.P Weber and G.W. Gokel, "Phase Transfer Catalysis in Organic Synthesis",
Springer Verlag, New York 1977.

R.A.B. Bannard, "Phase Transfer Catalysis and Some of its Applications to
Organic Chemistry", US. Dept. of Commerce NIRS AD-AO30 503 July, 1976.

H.H. Freedman, Pure and Appl. Chem, 1986 5_8, 857.

RM. Izatt and FF. Christensen, "Synthetic Multidentate Macrocyclic
Compounds", Academic press, New York, 1978.

N.A. Gibson and J .W. Hosking, Aust. J. Chem, 1965 1_8, 123.

(a) E. Laurent, R. Rauniyar and M. Tomalla, J. Appl. Electrochem 1984 1_4, 741;
(b) E. Laurent, R. Rauniyar and M. Tomalla, ibid, 1985 _l_§, 121.

SP. Ellis, D. Fletcher, W.M. Brooks and K.P. Healy, J. Appl. Electrochem, 1983
13, 735.

42.
43.

45.
46.
47.
48.
49.
50.

51.
52.

53.
54.
55.
56.
57.

58.
59.

61.
62.
63.

156

Z.Goren and I. Willner and H. Taniguchi, J. Org. Chem, 1984 42, 4755.
T.Kitamura, S. Kobayashi and H. Taniguchi, J.Org. Chem, 1984 42, 4755.
W.T. Ford, Adv. Polym. Sci., 1984 33, 49.

W.T. Ford, Polym. Sci. and Tech., 1984 a, 201.

DC. Sherrington, Macromol. Chem, 1984 3, 303.

J.W. Verbicky Jr., and EA. O’neil, J. Org. Chem, 1985 30, 1786.

E. Chiellini, R. Solaro and S. D’Antone, Polymer Sci. and Tech., 1984 24, 227.
Y. Iwai and M. Ueda, Polymer Sci. and Tech., 1984 24, 121.

(a) A.J. Dias and T.J. McCarthy, Polym. Mater. Sci. Eng., 1983 _4_9, 574; (b) A.J.
Dias and T.J. McCarthy, Macromolecules, 1984 l_7, 2529.

EM. Menger, Chem. Soc. Rev., 1972 _l_, 229.

K. Shinoda, R. Nakagawa, B. Tamamushi and T. Isemura, "Some
Physicochemical Properties of Colloidal Surfactants", Mir. Moscow, 1966.

RA. Rehinder and Zhur. Jses, K him. Obschch. Mendeleeva, 1966 11, 362.
P. Mukerjee, Adv. Colloid. Interface Sci., 1967 l, 241.

P.G. Duggan and W.S. Murphy, J. Chem. Soc., Perkin Trans. 1, 1976, 634.
P. Duhamel, J.Y. Valnot, E. Jamal, J. Tetrahedron Lett., 1983, 2863.

M. Pfau, G. Revial, A. Guingant and J. D’Angelo, J. Am. Chem. Soc., 1985 l_QZ,
273.

A. Enders, C hemtech, 1981, 504.

A.l. Meyers, D.R. Williams, G. W. Erickson, S. White and M. Druelinger, J. Am.
Chem Soc., 1981 _1_Q3, 3081.

K, Tomioka, K. Ando, Y. Takemasa and K. Koga, J. Am. Chem. Soc., 1984 _1_0_6,
2718.

S. Hashimoto and K. Koga, Tetrahedron Lett., 1979, 3495.
D. Enders and H. Eichenauer, Chem. Ber., 1979 _l_l_2, 2933.
H. Wynberg, Top. S tereochem., 1986 1_6, 87.

U. H. Dolling, D.L. Hughes, A. Bhattacharya, KM. Ryan, S. Karady L.M.
Weinstock and EU. Grabowski, ACS Symp. Ser., 1987 326, 68.

65.

67.
68.
69.
70.
71.

72.
73.

74

75.

76.
77.
78.
79.
80.
81.

82

83.
84.
85.
86.
87.
88.
89.

157

B. Bosnich, NATO ASI Series E "Asymmetric Catalysis", Martinus Nijhoff
Publishers, Dordrecht 1986.

E.V. Dehmlow, P.Singh and J. Heider, J. Chem. Research, 1981, 292.

DJ. Cram, and G.D.Y. Sogah, J. Chem. Soc. Chem. Comm, 1981, 625.

J. Balcells, S. Colonna and R. Fomasier, Synthesis, 1976, 266.

S. Colonna and R. Fomasier, Synthesis, 1975, 531.

R. Kinishi, Y. Nakajima, J. Oda and Y. Inouye, Agric. Biol. Chem, 1978 Q, 869.

R. Kinishi, N. Uchida, Y. Nakajima, J. Oda and Y. Inouye, Agric. Biol. Chem,
1980 14;, 643.

J. Heider, Doctoral Dissertation, T. U. Berlin, 1978.
U.H. Dolling, P. Davis and E.J. Grabowski, J. Am. Chem. Soc., 1984 106, 446.

. H. Wynberg and R. Helder, Tetrahedron Lett., 1975, 4057.

H. Hiemstra, PH.D. thesis, University of Groningen, Groningen, The Netherlands,
1980.

H. Wynberg and B.G.J. Staring, J. Chem. Soc. Chem. Comm, 1984, 1181.
H. Wynberg and B.G. Marsman, J. Org. Chem, 1979 _4_4_, 2312.

J .C. Hummelen and H. Wynberg, Tetrahedron Lett., 1978, 1089.

H. Wynberg and B.G. Marsman, J. Org. Chem, 1980 43, 158.

Y. Harigaya, H. Yamaguchi and M. Onda, Heterocycles, 1981 13, 183.

R. Helder, R.W. Laane, J.C.Wiering, J.C. Hummelen and H. Wynberg,
Tetrahedron Lett., 1976, 1831.

. G. Snatzke, F.L. Feringa, B. Greydanus, H. Pluim, H. Wynberg and B.G. Marsman, J.

Org. Chem, 1980 43, 4094.

B.G. Marsman, Ph.D. Thesis, University of Groningen, The Netherlands, 1981.
S.L. Regen, J. Am. Chem. Soc., 1975 21, 5956.

S.L. Regen, J. Am. Chem. Soc., 1976 28_, 6270.

S.L. Regen, J. Org. Chem. 1977, 42, 875.

S.L. Regen and A. Nigan, J. Am. Chem. Soc., 1978 190, 7773.

S.L. Regen and J.J. Besse, J. Am. Chem. Soc., 1979 _1_Q_l_, 4059.

S.L. Regen, J.C.K. Heh and J. Mclick, J. Org. Chem, 1979 44;, 1961.

90.
91.
92.

93.

94.

95.

96.
97.
98.
99.

100.
101.
102.
103.

104.
105.
106.
107.
108.
109.
110.
111.
112.
113.

158

S.L. Regen, Nov. J. Chem, 1982 629.
S.L. Regen, K. Fukunishi and B. Czech, J. Org. Chem, 1981 g, 1218.

M. Cinquini, S. Solonna, H. Molinari,F. Montanari and P. Tundo, J. Chem. Soc.
Chem. Commun., 1976, 394.

H. Molinari, F. Montanari and P. Tundo, J. Chem. Soc. Chem. Commun., 1977,
639 .

H. Molinari, F. Montanari, S. Quici and P. Tundo, J. Am. Chem. Soc., 1979 191.
3920.

(a) M. Tomoi and W.T. Ford, J. Am. Chem. Soc., 1981 123 3821; (b) M. Tomoi
and W.T. Ford, ibid, 1981 103 3828 .

F. Montanari and P. Tundo, J. Org. Chem, 1981 4_6_, 2125.

Y. Kimura and S.L. Regen, J. Org. Chem, 1983 _4_8 195 .

Y. Kimura, P. Kirszensztejn and S.L. Regen, J. Org. Chem, 1983 4_8, 385.
M. Tomoi, J. Poly. Sci. Polymer. Chem. Ed., 1985 21,49.

P. Tundo, Synthesis, 1978, 315.

P. Tundo and P. Venturello, J. Am. Chem. Soc., 1979 1m, 6606.

P. Tundo and P. Venturello, J. Am. Chem. Soc., 1981 123, 856.

(a) P. Venturello,P. Tundo and E. Angeletti, J. Am. Chem. Soc., 1982 M, 6547;
(a) P. Venturello,P. Tundo and E. Angeletti, ibid, 1982 M, 6551 .

A. Cornelius and P. Laszlo, Synthesis, 1982, 162.

A. kadkhodayan and T. J. Pinnavaia, J. Molec. Cataly., 1983 21, 109.

P. Tundo, J. Chem. Soc. Chem. Commun., 1977, 641.

P. Tundo and P. Venturello, Tetrahedron Lett., 1980, 2581 .

P. Tundo, P. Venturello and E. Angeletti, ls. J. chem, 1985 26, 283.

W.T. Ford, J. Lee and P. Tundo, Macromolecules, 1982 Q, 1246.

F. Montanari, S. Quici and P. Tundo, J. Org. Chem, 1983 4_8, 199.

SL. Regen, Angew. Chem, Int. Ed. Engl, 1979 L8, 421.

N. Oktani, C.A. Wikie, A. Nigan and S.L. Regen, Macromolecules, 1981 14, 516.
S. Colonna, R. Fomasier and U. Pfeiffer, J. Chem. Soc. Perkin Trans. 1, 1978 2, 8.

114.
115.
116.
117.

118.

119.

120.
121.
122.
123.
124.
125.
126.

138.
139.
140.
141.

142.
143.

144.
145.

146.

159

N. Kobayashi and K. Iwai, Makromol. Chem. Rapid Commun., 1981 2, 105.
S. Banfi, M. Cinquini and S. Colonna, Bull. Chem. Jpn., 1981 _5_4,, 1841.
G. Manecke and H. Winter, Makromol. Chem. Rapid C ommun., 1981 2, 569.

E. Chiellini, S. D’Antone and R. Solaro, Polym. Prepr. Am. Chem. Soc., Div.
Polym. Chem, 1982 23, 179.

DC. Sherrington and J. Kelly, Polym. prepr., Am. Chem. Soc., Div. Polym.
Chem, 1982 23, 177.

DC. Sherrington "Phase Transfer Catalysis in Polymer Chemistry", ed. C.E.
Carraher and L. Mathias, Plenum Press, New York, 249 1983 .

M. S. Chiles, D.D. Jackson and RC. Reeves, J. Org. Chem, 1980 45, 2915.
F. Rolla, W. Roth and L. Homer, Naturwissenschaften, 1977 Q, 337.

DC. Sherrington and J. Kelly, Polymer Sci.and Tech., 1984 24, 249.

Y. Kawakami and Y. Yamashita, Polymer Sci. and Tech., 1984 24, 263.

N. Kobayashi and K. Iwai, J. Org. Chem, 1981 16, 1823.

H. Hiemstra and H. Wynberg, J. Am. Chem. Soc., 1981 123, 417.

S. Landau Ph.D. thesis " Physical and Catalytic Properties of Hydroxy-Metal
Interlayered Smectite Minerals", 1985.

DE. Pearson, J. Am. Chem. Soc., 1950 22, 4169.
W.A. Jacolis and M. Heidelberge, J. Am Chem. Soc., 1919 4_1_, 2090.
EH. Cordes and RB. Dunlap, Acct. Chem. Res., 1969, 329.

I.V. Berezin, K. Martinek and A.K. Yatsimirskii, Russian Chemical Reviews,
1973, 787.

H. Komeili-Zadeh, H.J.-M. Dou, and J. Metzger, J. Org. Chem, 1978 43,156.

8. Colonna, S. Julia, A. Ginebreda, J. Guixer and A. Tomas, J. C. S. Perkin Trans.
1, 1981, 574.

S. Colonna, J. C. S. Perkin Trans. 1, 1978, 371.

(a) B. Boyer, G. Lamaty and J.-P. Roque and J. Solofo, Nouv. J. Chim, 1986 l_Q,
553; (b) B. Boyer, G. Lamaty and J .-P. Roque and J. Solofo, ibid , 1986 _1_0_, 559;
(c) B. Boyer, G. Lamaty and J .-P. Roque and J. Solofo, ibid, 1986 _1_Q, 563.

S. Colonna, S. Julia, J. Guixer J. Masana, J. Rocas, R. Annuziate and H. Molinari,
J. Chem. Soc. Perkin Trans. 1, 1982, 1317.

147.

148.
149.
150.

151.

160

H. Wynberg, S. Colonna and ABerto Re, J. Chem. Soc. Perkin Trans. 1, 1981,
547.

H. Wynberg and B. Greijdnus, J. C. S. Chem. Comm, 1978, 427.
H. Wynberg and H. Pluim, Tetrahedron Lett., 1979, 1251.

(a) D. Borrmann and R. Wegler, Chem. Ber., 1966 22, 1245; (b) D. Borrmann and
R. Wegler, Chem. Ber., 1967 $9.. 1575.

H. Wynberg and A.A. Smaardijk, Unpublished results.