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LIBRARY
Michigan State
University

 

 

 

This is to certify that the

dissertation entitled

DIPOLE MOMENT EFFECT ON PHOTOCYCLOADDITION
OF DOUBLE BONDS TO TRIPLET BENZENE RINGS

presented by

Jong-Ili Lee

has been accepted towards fulfillment
of the requirements for

Ph.D. degree in Chemistry

($.4/ww

v Mary ro essor J
Date M ' /7/ 8&7

 

MS U is an Affirmative Action/Equal Opportunity Institution

0-12771

 

 

PIACE IN RETURN Box to remove this checkout from your record.
To AVOID FINES return on or before date due.
MAY BE RECALLED with earlier due date if requested.

 

DATE DUE DATE DUE DATE DUE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

6/01 cJCIRC/DatoDuepes-pts

DIPOLE

DIPOLE MOMENT EFFECT ON PHOTOCYCLOADDITION OF DOUBLE
BONDS TO TRIPLET BENZENE RINGS

by

long-Ill Lee

A DISSERTATION

Submitted to
Michigan State University
In partial fulfillment of the requirements
for the degree of

DOCTOR OF PHILOSOPHY

Department of Chemistry

2001

DlPOl

T
substitutc
lm'estig:

reglO‘selt

Abstract

DIPOLE MOMENT EFFECT ON PHOTOCYCLOADDITION OF DOUBLE

BONDS TO TRIPLET BENZENE RINGS

By

Jong—lll Lee

The regioselectivity of the intramolecular [2+2] photocycloaddition of ortho-
substituted para-butenoxy benzaldehydes, benzonitriles and cyclic phenyl ketones was
investigated. This investigation probed the effect of dipole moment on the

regioselectivity of cycloaddition.

Ortho substituted p-butenoxybenzaldehydes with electron-withdrawing groups
and a weak electron-donating group (Al-F, AI-CF3 and Al-CH3) generate syn-addition
isomers, double bonds added toward substituents, while one with a strong electron-
donating group (Al-OCH3) generates an anti-addition isomer, with the double bonds
adding away from the substituents. Results show the interactions between the molecular
dipole and transition dipole on the exciplex state to be the major factor in determining
regioselectivity. The relatively low regioselectivity observed for Al-F is attributed to the

direction of the molecular dipole moment, which aligns close to the molecular axis.

pButc
methyl (Al-CL
antitonformz
compared to 1

moment.

Ortht
Vetting ratit
generate the
affording, h
light source

Stlecttt'ity ;

p-Butenoxy tetralone (TT) and chromanone (CR), that are analogues of ortho
methyl (Al-CH3) and methoxy (Al-OCH3) substituted p-butenoxybenzaldehydes with
anti-conformation, form anti-addition products. Opposite regioselectivity of TT,
compared to its analog Al-CH3, is attributed to its opposite direction of molecular dipole

moment.

Ortho substituted p-butenoxybenzonitriles produced both regioisomers with
varying ratios depending on the light source. Upon irradiation with 254 nm, all nitriles
generate the anti-addition products as major isomers, with only CN-CI-I3 and CN-OCH3
affording, minor syn-addition products in 16.7 and 18.2% respectively. Changing the
light source to 313 nm degrades the regioselectivity for all cases and a complete loss of

selectivity is observed for CN-CF3.

To
Jeong-Hee,
Yarim,
and

S unwoo

iv

The at
encourageme

chemist and 1

Appr

and for the L

ltzt‘t

the Wigner

The

Wilmin-

Acknowledgments

The author wishes to appreciate Prof. Wagner for his guidance, support, and
encouragement throughout the course of this research. He has molded me into a better

chemist and guides me to choose the right path.

Appreciation is also given to the Department of Chemistry for its excellent faculty

and for the use of its fine research facilities.

I take pleasure in thanking my fellow graduate students, and especially those of

the Wagner Group, for many enjoyable associations during my stay at Michigan State.

The author also thanks National Institutes of Health and Michigan State

University for generous financial support.

ABSTRACT]
ACK\O\\'l
LIST OF '
LIST OF

PART 1. l

LIBRtE
1.2. PHO'
1.2.1..
1.2.2.
1.3. PHO
1.3.1.
1.3.2.
1.3.3.
1.3.4.
1.3.5.
1.3.6.
1.4. 'H
1.5. Go

:1:
S;
"I

N

[Q 5.)

l-qu‘

..........

TABLE OF CONTENTS

 

 

 

 

 

 

ABSTRACT I
ACKNOWLEDGMENTS - - - - - - -------- V
LIST OF TABLES ---I_X
LIST OF FIGURES- - X
PART I. INTRODUCTION ...... 1
1.1 . BRIEF HISTORY ......................................................................................................... 1
1.2. PHOTOCYCLOADDITION OF BENZENE ........................................................................ 2
1.2.1. Modes of Photocycloaddition ............................................................................ 2
1.2.2. Empirical Rule for Photocycloaddition Modes Prediction ............................... 4

1.3. PHOTOCYCLOADDITION 0F TRIPLET BENZENE TO DOUBLE BONDS ........................... 6
1.3. 1. Nature of the Excited State of Substituted Benzene ........................................... 6
1.3.2. Triplet Phenyl Ketone ........................................................................................ 8
1.3.3. Biradical character of mt“ triplet state of acylbenzene ................................... 9
1.3.4. Biradical Intermediate .................................................................................... 12
1.3.5. Regioselectivity ................................................................................................ 13
1.3.6. Benzonitrile System ......................................................................................... 15

1.4. 1H NMR DATA FOR SOME PHOTOPRODUCTS ......................................................... 17
1.5. GOALS OF RESEARCH .............................................................................................. 24
PART 2. RESULT S- ------- . ------------- - - - - ............. 25
2.1. RING SUBSTITUTION ................................................................................................ 25
2.2. PREPARATION OF REACTANTS ................................................................................. 26

2.3. PHOTOCHEMISTRY OF 4-(3-BUTEN- 1-OXY)-2-MEIIIYLBENZALDEHYDE (AL-CH3) . 34
2.4. PHOTOCHEMISTRY OF 4-(3-BUTEN-l-OXY)-2-ME'IHOXYBENZALDEHYDE (AL-OCH3)

....................................................................................................................................... 38
2.5. PHOTOCHEMISTRY OF 4-(3-BUTEN- l -OXY)-2-FLUOROBENZALDEHYDE (AL-F) ....... 41
2.5.1. Irradiation of 4-fonnyl-2-fluoro-1 1 -oxabicyclo[6. 3. 0]undeca-1,3, 5-triene (Al-
F-COr). ...................................................................................................................... 45
2.6. PHOTOCHEMISTRY OF 4-(3-BUTEN-l-OXY)—2-TRIFLUOROMETHYLBENZALDEHYDE
(AL-CF3) ........................................................................................................................ 48
2.6.1. Irradiation of 4fonnyl-2-trifluoromethyl-1 1 -oxabicyclo[ 6. 3. 0] undeca-I ,3, 5-
triene (Al-CF3~C0t). ................................................................................................. 50

2.7. PHOTOCHEMISTRY 0F 4-(3-BUTEN- l .oxy)-2-METHYLBENZONITRILE (CN-CH3) 52
2.8. PHOTOCHEMISTRY 0F 4-(3-BUTEN- l -OXY)-2-ME’IHOXYBENZONI'I'RILE (CN-OCH3)

....................................................................................................................................... 57
2.9. PHOTOCHEMISTRY OF 4-(3-BUTEN- 1 -OXY)-2-FLUOROBENZONITRILE (CN-F) ......... 63

vi

ZRLDI
deC‘
2.9.2. 1711
deCl
2.10. PHOT1
11111101101
2m11
mdmi
2.11. P1101
2.12. P1101
2.13. C0311

PART 3. D.

3.1. REGlO
3.2. OVER;
3.2.]. F .
3.2.2. B
33. PHOT(

PART 4. E

{thug
4.2.6131.
1215
122(
1mm
{314
4.3.2. 4
I334
4344
4354
4.3.6. 4
4.3.7. 4
439g

2.9.1. Thermal chemistry of I~cyano-2-fluoro-8-oxatricyclo[7.2.0.09'5]undeca-2, 10-

 

 

diene (CN-F-CBt) ...................................................................................................... 69
2.9.2. Thermal chemistry of 1-cyano-1 1-fluor0-8-oxatricyclo[7.2.0.09'5Iundeca-2, 10-
diene (CN-F-CBa) ..................................................................................................... 71
2.10. PHOTOCHEMISTRY OF 4-(3-BUTEN- 1 -OXY)-2-
TRIFLUOROFLUOROMETHYLBENZONTTRRE (CN-CF3) .................................................... 73
2.10.1. Thermal chemistry of I-cyano-2-trifluoromethyl-8-oxatricyclo[7.2.0.095]
undeca-Z, 10-diene ( CN- CF 3-CBt) ............................................................................ 78
2.1 1. PHOTOCHEMISTRY OF 6-(3-BUTEN-1-OXY)-I~TETRALONE (TT) ........................... 79
2.12. PHOTOCHEMISTRY or 6-(3-BU'I'EN- 1 -OXY)— 1 -CHROMONONE (CR) ...................... 85
2.13. COMPUTATIONAL STUDIES .................................................................................... 89
PART 3. DISCUSSION -- - - ..... - - 91
3.1. REGIOSELBC'I'IVI‘I’Y ................................................................................................. 91
3.2. OVERALL MECHANISM ............................................................................................ 94
3.2.1. Formation of Exciplex ..................................................................................... 96
3.2.2. Biradical ........................................................................................................ 105
3.3. PHOTOCHEMISTRY OF BENZONITRILE DERIVATIVES ............................................. 1 10
PART 4. EXPERIMENTAL - - - - 112
4.1. INSTRUMENTATION ............................................................................................... l 12
4.2. CHEMICALS ........................................................................................................... 1 13
4.2.1. Solvents .......................................................................................................... 113
4.2.2. Chromatography Material ............................................................................ I 15
4.3. PREPARATIONS OF REACTANTS ............................................................................. 1 16
4.3.1. 4-( 3 -Buten-1 -oxy)-2—methylbenzaldehyde ..................................................... 1 I 6
4.3.2. 4-( 3-Buten-1 -oxy)-2-methoxylbenzaldehyde ................................................. 124
4.3.3. 4-( 3 -Buten-I -oxy )-2-fluorobenzaldehyde ...................................................... 126
4.3.4. 4-(3-Buten-1-oxy)-2-trifluoromethylbenzaldehyde ....................................... 131
4.3.5. 4-( 3 -Buten-I -oxy )-2-methylbenzonitrile ........................................................ 133
4.3.6. 4-(3-Buten-1 -oxy)-2-methoxybenzonitrile ..................................................... 135
4. 3. 7. 4-( 3 -Buten-I -oxy)-2 fluorobenzonitrile ........................................................ 139
4.3.8. 4-(3-Buten-I -oxy)-2-trifluoromethylbenzonitrile .......................................... 146
4. 3. 9. 6-(3-Buten-1-oxy)- I -tetralone ....................................................................... 150
4.3.10. 6-( 3 -Buten-1 -oxy)-1-chromonone ............................................................... 153
4.4 GENERAL PROCEDURES .......................................................................................... 157
4.5. IDENTIFICATION OF PHOTOPRODUCTS ................................................................... 158
4.5.1. Photolysis of 4-(3-buten-1 -oxy)-2-methylbenzaldehyde ................................ 158
4.5.2. Photolysis of 4-( 3 -buten-I -oxy)-2-methoxybenzaldehyde ............................. 160
4.5.3. Photolysis of 4~( 3-buten-I -oxy )-2-fluorobenzaldehyde ................................ 162
4.5.4. Photolysis of 4-(3-Buten-1 -oxy)-2-trifluoromethylbenzaldehyde .................. 166
4.5.5. Photolysis of 4-( 3-buten-1 -oxy)-2-methylbenzonitrile .................................. 169
4.5.6. Photolysis of 4-( 3 -buten-1 -oxy )-2-methoxylbenzonitrile .............................. 1 71
4. 5. 7. Photolysis of 4-(3-buten-1 -oxy)-2fluorobenzonitrile ................................... 1 75

vii

4.5.8. P11
4.5.9. 6-1
4.5.10. 6
4.6.CONIP1

REFERES

4.5.8. Photolysis of 4-( 3 -buten-1 -oxy )-2-trifluoromethylbenzonitrile ..................... 181

4. 5. 9. 6-( 3 -Buten-1 -oxy)- I -tetralone ....................................................................... 185
4.5.10. 6-( 3 -Buten-I -oxy )- I —chromonone ............................................................... I 88

4.6. COMPUTATIONAL ANALYSIS ................................................................................. 190
REFERENCE 191

 

viii

.l’umber

1.11121. 5131.
ORBIC‘I'C
1.11111: 2. SE
OXATRlC‘
1.11111: 3. SEL
meme
TABLE I. SE1
oxmuc
TABLE 5. TH.
TABLE 6. Sn
TABLE 7. GR
(AL-X1
1.11111: 8. D1
suasm
1111.19. G
(AL-X 1
TAIL: 10. '.
scam
TABLE 11.
BUYS
TABLE 12. t
BUB

 

List of Tables

Number Page
TABLE 1. SELECTED CHEMICAL SHIFTS AND COUPLING CONSTANTS OF SOME 4-ACETYL-1 1-
OABICYCLo[6.3.O]UNDECA-l,3,5-TRIENE (COT) DERIVATIVES ................................. 18
TABLE 2. SELECTED CHEMICAL SHIFTS AND COUPLING CONSTANTS OF SOME 4-ACETYL-l 1-
OXATRICYCLo[6.3.0.0"4]UNDECA-2,5-DIENE (CB) DERIVATIVES .............................. 20
TABLE 3. SELECTED CHEMICAL SHIFTS AND COUPLING CONSTANTS OF SOME 4-ACETYL-1 l-
OXATRICYCLO[6.3.O.03‘6]UNDECA-1,4-DIENE (LCB) DERIVATIVES ........................... 22
TABLE 4. SELECTED CHEMICAL SHIFTS AND COUPLING CONSTANTS OF SOME 4-ACETYL-1 1-
OXATRICYCLo[6.3.O.0"6]UNDECA-2,4—DIENE (CH) DERIVATIVES ............................. 23
TABLE 5. THESIS NOTATION OF PHOTOREACTANTS ............................................................ 25
TABLE 6. SINGLET AND TRIPLET ENERGY OF REACTANTS. ................................................. 89
TABLE 7. GROUND STATE ENERGY OF ORTHO SUBSTITUTED P-BUTENOXYBENZALDEHYDE
(AL-X) ....................................................................................................................... 90
TABLE 8. DIPOLE MOMENTS AND ENERGY OF ANTI/SYN CONFORMER OF ORTHO
SUBSTITUTED P-BU'I‘ENOXYBENZALDEHYDE(AL-X). .................................................. 90
TABLE 9. GROUND STATE ENERGY OF ORTHO SUBSTITUTED P-BUTENOXYBENZALDEHYDE
(AL-X) ....................................................................................................................... 98
TABLE 10. TRIPLET EXCITED STATE ENERGY AND DIRECTION OF DIPLOE MOMENT OF ORTHO
SUBSTITUTED P-BUTENOXYBENZALDEHYDE (AL-X) .................................................. 99
TABLE 11. ENERGY (IN KCAt/MOL) OF BIRADICALS (BR) OF ORTHO SUBSTITUTED P-
BUTENOXYBENZALDEHYDE ...................................................................................... 107
TABLE 12. CALCULATED ENERGY OF CH AND CO OF ORTHO SUBSTITUTED P-
BUI'ENOXYBENZALDEHYDE. ..................................................................................... 109

ix

.l'umber

FIGLRE 1. 51
11011112 2. D1
(AI-X1
11011115 3. Et
BLTEXC
FIGLRE 4 E0
EICIPU
Item: 5. C.
FIGLRE 6. D'
X) FOR

List of Figures

Number Page
FIGURE 1. STRUCTURE OF PHOTOREACTANTS .................................................................... 25
FIGURE 2. DIPOLE INTERACTION OF ORTHO SUBSTITUTED P-BUTENOXYBENZALDEHYDE
(AL-X) WITH SYN CONFORMER FOR SYN ADDITION. ................................................. 100
FIGURE 3. EQUILIBRIA BETWEEN TWO ADDITION MODES OF ORTHO SUBSTITUTED P-
BUTENOXYBENZALDEHYDE (AL-X) ON EXCIPLEX STATE. ........................................ 101
FIGURE 4 EQUILIBRIA BETWEEN Two ADDITION MODES OF BUTENOXYTETRALONE (IT) ON
EXCIPLEX STATE. ...................................................................................................... 103
FIGURE 5. CALCULATED GEOMETRY OF P-BUTENOXYBENZALDEHYDE. ........................... 105
FIGURE 6. DIPOLE INTERACTION OF ORTHO SUBSTITUTED P-BUTENOXYBENZONITRILE (CN-
X) FOR SYN ADDITION. ............................................................................................. 1 10

11 1811

 

aromatie'tty (it

during photol

l.l. Brief 11'

FIN;

“11011112 (I

Bry-
Blythe lit

'm 1959.3

311

and Sl’nth

Part 1. Introduction

It is well documented that the benzene ring has a strong tendency to maintain its
aromaticity during the thermal chemistry of benzene, while benzene loses its aromaticity

during photoinduced chemical reactions.
1.1. Brief History

Fritzsche reported the first photodimerization of an aromatic compound in 1866

exploring anthracene photodimer.l

Bryce-Smith made the landmark discovery of photoisomerization of benzene to
fulvene in 1957,2 and reported the first photocycloaddition of excited benzene to alkenes

in 1959.3

© 254 nm
———>
50 °C

Since the initial discovery, a variety of mechanism studies have been carried out

and synthetic applications were also extensively searched. 4' 5' 6' 7

lnl9

 

found that ph
cycloadditior
photoproduct

by secondar}

 

1‘2 PITOIOC)|

1.2.1. MOdes

Irrad

formaIlOn of

substitution

In 1987 Wagner and N ahrn discovered a new [2+2] photocycloaddition. They
found that phenyl ketones with the lowest mt* triplet states undergo intramolecular
cycloaddition to double bonds to produce bicyclo[4,2,0]octa-2,4-dienes as initial
photoproducts. The initial photoproducts then undergo thermal rearrangement followed

by secondary photoreaction to produce a cyclobutene.8' 9' '0

O
hv A hv \
—-> O = 1
Q 0
o O
\J

 

>1

0

1.2. Photocycloaddition of Benzene

1.2.1. Modes of Photocycloaddition

Irradiation of benzene at 254 nm in the presence of an alkene can lead to
formation of 1,2-(ortho), 1,3-(meta), and 1,4-(para) cycloadducts depending on the

substitution pattern of the arene and alkene.

©+H -"-"-* CD + 4? + (D

1 ,2-adduct 1 ,3-adduct 1,4-adduct

 

For 31
the products.
occur with v;
cycloadditio

W112
meta photo:
1966.

W11
ClTlopente
Smith. Gil

"1910 phor.

For all modes of cycloaddition, the stereochemistry of the alkene is preserved in
the products.11 Generally, both ortho10 and metal2 photocycloadditions are facile and
occur with various substituents on the aromatic rings and double bonds. In contrast, para
cycloaddition is very inefficient and rarely observed.

Wilzbach and Kaptan” and Bryce-Smith, Gilbert, and Orger” discovered the
meta photocycloaddition of benzene to alkenes independently and simultaneously in
1966.

Wilzbach and Kaplan reported that irradiation of benzene with a 10% solution of
cyclopentene produced a 1:1 ratio of adducts through the meta cyclization mode. Bryce-
Smith, Gilbert, and Orger reported that irradiation of cis-cyclooctene in benzene gave a

meta photocycloaddition adduct.

Regioselectivity was demonstrated for benzene with bearing either electron-donor
group or electron-withdrawing groups. Srinivasan and Subrahmanyam observed
intermolecular meta photocycloaddition of the double bond generally occurs at the 2- and
6- positions of the benzene ring, relative to the electron donor group.15 However, as the
size of donor groups increases, the double bond adds to the 3- and 5-position relative to
the ring substituent. Comelisse observed regioselectivity with electron-withdrawing
groups on the benzene has a strong preference for position 2 and 4 Without adduct at

position 1.16

Regiost
Addition react
l3—addttion a

undergoes 2.6

Comp
mMmmn
tycloadditior
such as addit
presence of
"WI Cycloa
ltTadiatiou (

"13101 pl'OdI

Regioselectivity for intramolecular photocycloaddition has also been studied.
Addition reactions of S-phenylpent-l-ene and its derivatives shows two principal modes:
1,3-addition and 2,6-addition, Gilbert and Taylor‘7 observed that S-phenylpent-l-ene

undergoes 2,6 as well as 1,3 addition in a ratio of 72:28.

Compared to other cycloaddition modes, para cycloaddition has drawn little
attention to investigate the mechanistic nature of this pathway. Generally, para
cycloaddition shows low efficiency and became the major pathway in only a few cases,
such as addition of dienes and allenes to benzene.18 When benzene was irradiated in the
presence of isoprene, the para cycloadduct was produced as the major adduct with the
meta cycloadduct as the minor product in the ratio of 4:1 respectively. Similarly,
irradiation of cyclonona— 1 , 2-diene in benzene produced the para cycloadduct as the

major product. '9’20

1.2.2. Empirical Rule for Photocycloaddition Modes Prediction

Some empirical rules to formulate factors that affect the regioselectivity of this
photocycloaddition were proposed by several researchers.

Bryce-Smith postulated that differences in ionization potentials (AIP) between the
benzene ring and the alkene could be used to predict the mode of the cyclization.21 Ortho

cycloaddition is preferred with a strong donor and acceptor alkenes (9.6 eV < [P < 8.65

cV) while me

and alkenes l

Houl
orbital inter;

alkene is eit

Mat
cycloadditi
mechanism
MOI of cl:
materials.
Sfineral. th

and ClCCIrt

Gleam” r
methoxy}
Photocyc
gives a 2
memo“

respect“

eV) While meta cycloaddition is preferred in the reactions between benzene (IP=9.24eV)

and alkenes having IP’S ranging from 9.6 eV to 8.65 eV.

Honk derived the same conclusion as Bryce-Smith and Gilbert but on the basis of
orbital interactions. They also found that the ortho cycloaddition is favored when the

alkene is either a better donor or a better acceptor than benzene.22

Mattay23'24 has also presented an empirical correlation between the modes of
cycloaddition and the free enthalpies of electron transfer based on the exciplex
mechanism and the Weller equation. According to Mattay’s rule, the Gibbs free energy
(AG) of electron transfer can be accurately calculated from redox potentials of starting
materials, excitation energy of the excited species, and coulombic interaction energy. In
general, the mode of cycloaddition changes from meta to ortho when AG is 1.4-1.6 eV

and electron transfer predominates when AG 5 0.

Gilbert demonstrated this empirical rule in photoreactions of benzenes with both
electron releasing and electron Withdrawing substituents. Photocycloaddition between 4-
methoxybenzonitn'le and cis-cyclooctene produces the endo meta cycloadduct while
photocycloaddition between electron rich ethyl vinyl ether and 4-methoxybenzonitrilc
gives a 2:1 mixture of ortho cycloaddition products, l-cyano-8-ethoxy-4-
methoxy[4.2.0l‘6]octa—2,4-dienc and 4-cyano-7-ethoxy-1-methoxy[4.2.0]octa-2,4-diene

respectively.25

1.3. Photo

1.313.311

CannOt be
orbitals. T
ftpresem
‘Ps‘l’s - I
group 111

511138111111

CN OMe

254 nm ‘03 /
aOEt M90 NC \ 0E1
MeO-.—CN
OMe

254 nm

0

 

 

 

 

CN

1.3. Photocycloaddition of Triplet benzene to Double Bonds

1.3.1. Nature of the Excited State of Substituted Benzene

Since its frontier orbitals are degenerate the actual frontier orbital of benzene
cannot be described with a single frontier orbital but rather combinations of four frontier
orbitals. The lowest excited triplet (TI) and second lowest excited singlet (S2) is
represented as ‘I’3‘I’4+ ‘1’2‘1’5 (Em) and the lowest excited singlet (81) is represented as
‘1’3‘1’5 - 95%; (B2,). 26 Substitution on the benzene ring with an electron-withdrawing
group like cyano or acyl group simplifies the description of the excited states of
substituted benzenes by removing the degeneracy of the frontier orbitals. If an electron-
withdrawing group stabilizes ‘1’4 and destabilizes ‘1‘3 then the lowest excited triplet, 3B1“,
(Tl) would be mostly a ‘1’3‘1’4 component. Carbons l and 4, top and bottom carbons on the

ring would possess high electron density.

Gen
distribution
kinetics. so
and Himta:

S13'1“ densit

basis 01 a]

spin dc“;

Set .
roe .

1,12 1/4‘ \1/4
. v
1/12 — 1/4K y1/4 5

1/3
mfijm 4+ + 1/12/+\1/12
W + ' —
1/4 1/4 1/12|\'/‘1/12 W3
1/3

Generally, it is very difficult to know the exact electronic charge and spin density

 

distribution of excited states. However, it can be predicted from reaction products,
kinetics, some Spectroscopic analysis, and quantum mechanical calculations. Wagner27' 28
and Hirota29 independently found that ortho and para to the nitrile group has the highest

spin density in triplet benzonitriles.

O
c 0.90 c c
1
0.12 G <—> 6 2
0.034 5 3
0.93 4

Wagner pointed out that triplet benzonitrile is essentially a 1,4 diradical on the
basis of analysis of the EPR spectra of triplet fluorobenzonitriles. The study showed that

spin density on the carbon (C4) para to the cyano group is close to unity as shown above.

This stron g1)
structure for
Paquc
I-methane rt
electron witl
the rearrang'

mmmn

1.3.2. Tripl

Phi
intersysten
The losses
Patterns 01
Clem-On O

militaHiL

This strongly suggested that a quinoidal structure is the most dominant valence bond
structure for the benzonitrile triplet state.

Paquette and co-workers30 reported several examples of regiospecificity in the di-
tt-methane rearrangements of benzonorboradienes substituted by electron donating or
electron withdrawing groups. They have shown that cyano and acetyl substituents direct
the rearrangement such that the double bond bridges to the benzene ring ortho or para but

not meta. This suggests that the excited state is a 1,4 diradical.

1.3.2. Triplet Phenyl Ketone

Phenyl ketones are known to reach their triplet States with fast efficient
intersystem crossing rate (k 15,; ~10"sec", <I>isc=l) Via the n,1t* lowest Singlet state.3 1' 32
The lowest triplet of phenyl ketones could be either n,1t* or 1t,tt* depending on the
patterns of ring substituents. The n,1t* transition is a result of excitation of a non-bondin g
electron of oxygen to the W" orbital of the carbonyl group and produces an alkoxy
radical-like excited state.”‘34 On the other hand, It,1t* transition is made by the excitation

of an 1! electron to 112* of whole 1: bond system of the molecule and 113,112“ triplets show

little radical-like reactivity. This is because of charge-transfer components and a lack of

strong spin localization on the carbonyl oxygen.”36

Generally, unsubstituted alkyl phenyl ketones have n,1I:* lowest triplets about 3
kcal per mole lower in energy than their 1t,1t* triplets. However electron-donating

substituents at any ring position lower TI,Tt* and raise n,1t* transition energies to generate

attr‘ losses
substituents
withdrawing

M“ triplet b

 

 

enough to in

1.3.3. Biradi

Wag
triplet benzt
miles of t
lml’amolec'
States Whil
Cycloaddit
attributed
"’7‘: triple
almost fut

a 1t,1t* lowest triplet state.l6 On the other hand, inductively electron-withdrawing
substituents lower n,1t* transition energies relative to It,tt* energiesm’m'38 Para electron-
withdrawing substituents like carbonyl and nitrile groups lower 1t,1t* triplet energies and
Tut“ triplet becomes the lowest triplet. Meta substituents do not stabilize 1t,1t* triplets

enough to invert triplet levels.39

1.3.3. Biradical character of It,1t* triplet state of acylbenzene

Wagner and Nahm discovered the first intramolecular 1,2-photocyc1ization of a
triplet benzene to an olefin during their study of the intramolecular quenching of 1t,tt*
triplets of ketones with remote unsaturated tethers.8' 9 They found that double bonds add
intramolecularly to the benzene moiety of phenyl ketones with the lowest 1c,1t* triplet
states While phenyl ketone with the lowest n,tt* triplet states did not Show any modes of
cycloaddition reactivity. The difference in reactivity for the two types of triplets is
attributed to their different spin densities at the para position to the carbonyl group. The
n,1t* triplet has only partial radical character at the para position while the It,tt* triplet has
almost full radical character at the para carbon. Valence bond representations of two

triplet states for an aryl ketone are shown below.27

Botl
intramolecu
reactivity. T
position in t;

llllle Spin dc

mm
:o: :0: 30°
<——> Q. <—»
n R R

3112.1?“

Both ortho and para-substituted ketones with the 1t,1t* triplet state undergoes
intramolecular ortho cycloaddition, but meta-substituted ketones do not Show any
reactivity. This is attributed to the amount of unpaired electron density at those three
position in the 1t,1t* triplet; unlike ortho and para positions, the meta position has very

little spin density.28

Wagner and Sakamoto40 demonstrated the effect of spin density on the reactivity
of photocycloaddition reaction by irradiation of both 1-butenoxy-2-acetonaphthone and
2-butenoxy-l-acetonaphthone. Two acetonaphthone promoted ortho photocycloaddition
from their tt,1t* triplet states. Due to the different spin density, two isomer a and b
showed the large kinetic differences. A faster reaction rate for isomer a than isomer b is
attributed to the higher unpaired electron density on the or positions versus the [3 positions

of naphthalene ring in triplet states.

10

 

 

Wagr

adding to the

the Urbirad

NO 0 m
—-—->
a
O m
b

Wagner proposed that the 1t,1t* triplet behaves like a biradical, one radical site

   

0

adding to the remote double bond the way a S—hexenyl radical would cyclize, generating

the 1,4-biradical (BR) that cyclizes to form CH as shown below.-

5! a»!
08' \ O \ 0‘ \
we <—» >430 —» we
R R R
1C,1t* State
0 o
<——
R O R

 

CH

11

1.3.4. Birad

 

 

too
which is 101
remote dout
initial photo

material cis-

 

intermediate

W Carried
has Obsen'.

Strongly so

0 ‘
TE
1C

0

1.3.4. Biradical Intermediate

Upon irradiation of phenyl ketone, a charge transfer complex (CT) is formed,
which is followed by the cycloaddition of the radical center para to the acyl group to the
remote double bond. The addition generates a 1,4 biradical which will either close to the
initial photoproduct or cleave to give starting material. During decay to the starting
material cis-trans isomerization was observed supporting the presence of a biradical

intermediate during the course of reaction.8

The photochemisz of lCP which, has a cyclopropyl group at the double bond,
was carried out to support the idea of a 1,4 biradical intermediacy.“’l No cyclopropyl ring
was observed intact after irradiation of lCP. The opening of the cyclopropyl ring

strongly suggests the existence of a biradical intermediate as shown below.

\ hV/MBOH O

O
O D
j C O
1 CP V
30%

 

 

   

Not Found

12

1.3.5. Regit‘

lntIt"
creates two
from the thii

Elect

 

 

alkene moie
the remote d
hladltouru 1
substituent 1

Retinal and

1.3.5. Regioselectivity

Introduction of a third substituent on the benzene ring of the p-alkenoxy ketones
creates two possible directions of cycloaddition, one added toward and one added away
from the third substituent.

Electron withdrawing and alkyl groups ortho to the alkenoxy group cause the
alkene moiety to add toward the third substituent. Strong electron donating groups force
the remote double bond to add away from the third group. Wagner, Sakamoto and
Madkour42 suggested that this regioselectivity reflects inductive effects of the third
substituent both on the nature of initial triplet state cycloaddition and the competing

thermal and photochemical reactions of the resultant photoproducts.

”case—03014:!"
We X233? is

13

Wag

methyl is a _

Wag
little steric 1.

electronic n;

Occurs towai

 

Wagner pointed out that the preference for addition toward isopropyl rather than

methyl is a Steric effect.IO

i-Pr /

 

Me

Wagner and Smart observed a higher degree of regioselectivity in a system with
little Steric interaction between the third group and the alkene tether.43 Regardless of the
electronic nature of the third substituents ortho to the acetyl group, photocycloaddition

occurs toward them. Only fluorine was found to give 9% of the other isomer.

MAI—O34

X=Me, OMe, era
X=F (9%) and F (91%)

Wagner suggested that the direction of the carbonyl induced the regioselectivity
based on the fact that fluorine, the smallest substituent studied, is the only one that
showed both regioisomers. Wagner and Smart43 also observed that indanone, whose
carbonyl is pointing away from the alkyl group, generated only regioisomers with the

double bonds adding away from the substituents.

l4

 

1.3.6. Benzt

Gilbl

 

 

photocycloa

CN

©OME

to

intramolect
' 45
Gllben at

by 1’3 (lien

° 1

hv
CD ——>

O

 

1.3.6. Benzonitrile System

Gilbert reported that 2-methoxybenzonitriles undergoes efficient intermolecular

photocycloaddition with electron rich alkenes.44

NC OEt NO

ON
OMe
t ——> ‘—-
OMe A

0E1

2’ and 4’ cyano substituted 4—phenoxybut-l-ene were shown to undergo
intramolecular ortho cycloaddition upon both direct irradiation and triplet sensitization by
Gilbert45 and Wagner“, respectively. The forrnation of the cyclooctatriene was quenched

by 1,3 dienes whereas its intramolecular cyclization to cyclobutene was not quenched.

'FI
hv hv R
/’ ‘ 0 = O —-> 1:03
— 4' at 254 nm
Ft 2' at >290 nm Ft 0 -R O

in MeCN
or
2' in acetone FI=CN, R'=H
111:}: 00,51 R=H, FI'=CN

 

15

 

McCullough47 observed that naphthonitrile systems Show the same type of
cycloaddition. When 2,3-dimethyl-2-butenyl(l-cyano-2-naphthyl) methyl ether in
benzene was irradiated, a 20:1 mixture of two ortho cycloaddition products, c and (1,
respectively were detected as shown below. During the reaction no ring opening to
cyclooctatriene was observed. Prolonged irradiation removed the initially formed major

product and produced only one cycloadduct, d that was initially formed as the minor

CN CN
Be::ene +

c d

16

1.1 ‘11 N)

 

in 11
‘11 sane d.
I
understand:
The follow:
products 111.

Wagner ms

chemical sh

 

1.4. ‘H NMR Data For Some Photoproducts

In the process of characterizing photoproducts so as to differentiate regioisomers,
lH NMR data analysis played a crucial role throughout this research. Therefore, thorough
understanding of the ‘H NMR spectra for many similar skeletal structures is necessary.
The following tables are a collection of key 1H NMR data of some ortho cycloaddition
products that are CH, CO, CB and LCB, previously reported by other members of the
Wagner research group. Product assignments depended heavily on comparison of NMR

chemical shifts and coupling constants.

17

Table 1. l
oabicyclol."
l

‘ Chemical 5’

1’:

ezntzst,
2.38 '
It

01

CDC];

6.021110.

    

6.361113) .

 

 

Table 1. Selected chemical shifts and coupling constants of some 4—acetyl-l l-
oabicyclo[6.3.0]undeca-l,3,5-triene (COT) derivatives

 

Chemical Shifts (coupling constants)

Ref.

Chemical Shifts (coupling constants)

Ref.

 

 
  
 

  
   
  

 

    
 
 

 
 
  

 

 
  
 

 

 

 

 
   
   

 

692(12566) 9 5,95 2.3503, 6, 6, 2) 43
3.06 11.3, 7.9.4 2.5113. 4. 3. 2)
627025 I (:26 ) 3, 1.96
2.36 o 2.1' '2‘, . 2.13
o ’ \5.4(6.6) (12' 9’ 6'5)
7.0(6.8) o I \5.4(6_8) 4.202, 9, 5)
CDCls 7.12(8.1) 4.28112. 9. 5)
CD3OD
6.02(11.3, 7.9, 7.9) 2-25' 2-56 43 H 0’1'93U‘S) 43
I 3.07 3 9H3
6.36(11.3) I 161,219 698“. 1.5 7 CH3
""CH3
0
\5.36(8.0, 2.2) o
639‘s”) 7.116.525 £219)
CDC13
CD3OD
206(16, 5.5.2) 49 5.88(qdd, 1.5, 9.5.6.7) 49
1.67116. 9) 209(14, 7, 4)
/ 2.81 \ //3.03
5.92(br s) / 3.5 (8 8 5)
3.7(6, 7, 7)
0 \5.36(s)
C6136
o 22303.4, 6.3) 50 50
2.04034, 1.9)
7.13(6.2)
5 1o \ 4.02
13 2\3 ,/ 0 4.13
575‘ -6- )1 \ 5.34(8.8, 1.9)
CDC}3 CDC13

 

 

 

 

l8

 

 

Table l. (1

HI

—-4

7.05(6.1) 1
1.
5.73 \
(132. 6.1 )
6.0‘

CDC];
524(9.3,7.

 

l

 

H300

 

Table 1. (Cont’d)

 

 

 

 

 

 

 

 

43 5.92(9.5,6.3,1.6) 49
(13.2.6.1)f \5.33(9.4, 2.5) 1' \ ( )
5.15.1
6.01(13.2, 9.4) 6'95 (5")
CDCI3 CD03
5.24(9.3,7.1) 49 5.85(17.1,9.6,7.5) 49
o 7 x
_1 , .. 5.23(6.03,
7.19(5.34) 5 4(53405) 7.3(6.03,0.75) 31.0.75)
CDC13 CDC];
6.8(9.2,6.5,1.6) 49 5.94(13.1,5.94) 51

 

7.2(4.6)
CDC13

 

6.28(13.2,
2.19)

  

 

 

 

19

 

Table 2.

oratricyclt

.____L_
Chemical

1 —

58512.7).

 

Table 2. Selected chemical shifts and coupling constants of some 4—acetyl-1 l-

oxatricyclo[6.3.O.01'4]undeca-2,5-diene (CB) derivatives

 

 

 

 

 

 

 

   
 

Chemical Shifts (coupling constants) Rcf- Chemical Shifts (coupling constants) Ref.
0 5.83(d,11.1) 50 o 5.75(10.2, 3) 43
5.65(2.7) \‘f 'l I 5.59““) 62712-8) \{ is, 5.65
4
[He (10.2.4522)
0‘“ : O“ .=
6. 2.7 5 H 6.27(2.6) 9: H
06‘ ) >3; ‘8" \ 2.39
3.51(m)
3.64(6, 6.2.7)
C6D6 CD30D
5.43 ,1.5 43 5.47 ,1.4
o (q 117 \//°/ (9 )_ 4s
. 6.31(2.9) ., CWT—(L4)
. ‘—2.22
o = /o‘° CH3 (7.4 1.4)
6.5(2.9) w CH3 6..41(2 9) E123; CH3 ’
H36 H36
CD30D CD301)
o 5.7(9.6,2.9) 48 5.7.4(101 3.1) 43
6.21 \f ’/ 3508168 26) 6.29(2.8)\/ 5.61
(3.0) :H ' ' ' ' ° ‘ 13 (10.1.6.6, 2.3)
‘ ‘ T‘ ‘89 17.26.13. 2
6.33 (,5: '3013311155968) 642128)" H\ ‘ 226 )
(3‘0) CH3 (15.,9 2.9 2.6) H36 2.51 (17'7'2)
(12.6, 8, 6, 2)
CD3OD CD3OD
H/ 1.58(1.5) 49 1 .49(1_5) 5.62(br 8) 49
5.97 0C 3 C
(15) \€ add 15 42 4 a
@(q""’) 5.63 /.~,°‘~1.7(m)
~ _ ‘——1.59(m) (dq0.6,1.5?\._u=‘ H 2.06(11.1)
0‘ .-: 1.8(m)
‘42:.- “\ /
/ 1.81m) 3.57(9, 6, 7)
3.62(6, 7, 6) 3.65t8.4. 8. 3)
3.72(9, 6, 6.5) CeDe
C6D6

 

   
     

 

 

 

20

 

 

CD30D

 

‘

53512.9“

’4
5.51294)

 

CD30D

 

Table 2. (Cont’d)

 

   
 

   

 

 

628(3 0 - , 5.54 (4.4) 6 23(2-97 I 4.75(6.1.3.2)
“ ‘. ‘ 6
6.50(3.03)° 5 6.35 2 97 O
V23— ( - ) VEL-
li'i.80(m) 43.8mm)
CD309 CD3OD
0 F 49 6.58(2.88) 51
6.35(2.9) N?

    
    
   

, 5.31 (15.6,
6.5.2.8)

6.5(2.94) O

/

3.79

095

CD3OD

 

 

 

 

 

21

 

 

Table 3.

oxauicyci

3......—
Chemlcal

5.B1(2.8

6.04(2.8. C
3

 

 

(2.8, 0.9)

3.49
(6.6,

CD.

 

 

Table 3. Selected chemical shifts and coupling constants of some 4-acetyl-11-
oxau'icyclo[6.3.0.03'6]undeca-l ,4-diene (LCB) derivatives

 

Chemical Shifts (coupling constants)

Ref.

Chemical Shifts (coupling constants)

Ref.

 

    

 

 

  

 

 

 

o 165(14) 9 50
5.61(2.6 \( / CH
’ 6 7 a 192.1
In 0‘ 3.77
6.04(2.6, .9) / .
3.54 4.97 (2.5. 8.5. 8.5)
3.32 4.98(6-6) (6.4,) (6.4.2.7)
(6.6.0.9)
C6D
Cd). 6
2.12(1 3. 5) 49 1 .82(14) 43
224(13, 9) 2.1 1 (14)
o
6.11(2.6) \y / H .— 2.56
[a ‘||9§ "n.<
/ o \
6.15(2.8) / 3.37
3.42 4.72(6.6, 2.5) 3.49 4.76(6.6)
(6.6, 1.7) (6.6, 0.9)
CD30D CD3OD
1.62(14) 51 51
2.11(14)

 

3.49

4.76(6.6)
(6.6, 0.9)

C6D6

 

 

 

 

 

22

 

Table 4

oxatriqclI

. —-

Chemical

6|

5.69
(9.6, 5.6)

 

5.53
(9.8, 5.6‘

 

 

Table 4. Selected chemical shifts and coupling constants of some 4-acetyl-l 1-
oxatricyclo[6.3.0.0"6]undeca-2,4-diene (CH) derivatives

 

Chemical Shifts (coupling constants)

Ref.

Chemical Shifts (coupling constants)

Ref.

 

     
  

 

 

 

  

 

 

5.34(9. 6) 3 6.69(s) 49
5.69
(9.6, 5.6) \V0
2.47
5 53 “(6.5, 1 6)
(9. 6, 5. 6)
5. 43
(9. 6) 68"")
C6D6
6.26(5.4) 52 o 49
\
6. 27(10) [0
5.31 (10)
CDC13 CDC”
49 o F 49

 

 

  

6.53(10,7.6)
5.3(10,2.34)
CDCI3

 

 

 

23

 

 

1.5. 606!

Ti

cycloaddi'

a To deter

 

 

With 5
b. To stud:

and nil

1.5. Goals of Research

The goal of this research is to understand the mechanism of photochemical

cycloadditions of excited triplet benzene to alkenes. The main focus of this study is:

a To determine the regioselectivity of the initial ortho photocyclization onto bezene rings
with substituents ortho to carbonyl and cyano groups.
b. To study the effect of the dipole moment of electron withdrawing groups such as acyl

and nitrile on the corresponding regioselectivity.

24

 

 

11. Ring

Table 5. T

Ring SI

W=aldehy

deh‘

‘1'
~

4% A... N. 2 - N. C a
W W W “W “W n“ w w

W

Part 2. Results

2.1. Ring Substitution

 

 

 

Figure 1. Structure of photoreactants

Table 5. Thesis notation of photoreactants

 

 

 

 

Ring Substituents Name Thesis
Notation
W=aldehyde, R=CH3 4-(3-Buten-l-oxy)-2-methylbenzaldehyde Al-CH3
W=aldehyde, R=OCH3 4-(3-Buten-l-oxy)-2-methoxybenzaldehyde Al-OCH3
W=aldehyde, R=F 4-(3—Buten-1-oxy)-2-fluorobenzaldehyde Al-F

 

W=aldehyde, R=CF3 4-(3-Buten-l-oxy)-2-trifluoromethylbenzaldehyde Al-CF3

 

 

 

 

 

W=CN, R=CH3 4-(3-Buten-1-oxy)-2-methylbenzonitrile CN-CH3
W=CN, R=OCH3 4-(3-Buten-l-oxy)-2-methoxybenzonitrile CN-OCH3
W=CN, R=F 4-(3-Buten-l-oxy)-2-fluorobenzonitrile CN-F
W=CN, R=CF3 4-(3-Buten-1-oxy)-2-trifluoromethylbenzonitrile CN-CF3
W, R=COCH2CH2CH2 6-(3-Buten-l-oxy)-1-tetralone 'I'T

 

 

W, R=COCH2CH20 2,3-Dihydro-7-(3-buten-l-oxy)-4H-benzopyran-4-one CR

 

 

 

25

 

 

 

2.2. Prep

emenficai
mfimw
phenol )1.-

name)

bHMMm

 

MmHo,

N

OH

(5

MH
Wet
0=c

 

 

 

2.2. Preparation of Reactants

4-(3-Buten-l-oxy)-2-methylbenzaldehyde (Al-CH3) was prepared by
esterification of cresol with acetyl chloride in pyridine and benzene at 0°C followed by
Fries rearrangement49 with aluminum chloride in nitrobenzene at 0°C. The resulting
phenol was alkylated using 4-bromobutene with potassium carbonate in refluxing acetone
followed by oxidation of the acetyl group with iodine. The carboxylic acid was reduced
by lithium aluminium hydride (LAH) to the alcohol which was then oxidized to 4-(3-

buten—l-oxy)-2-methylbenzaldehyde by pyridinium chlorochromate (PCC).

 

0 OH
OH

O
acetyl chloride, pyridine A|C|3
p +
benzene. 0°C a nitrobenzene, 0°C

 

 

 

 

 

 

0
0 o
\ 1. l2, pyridine \ potassium carbonate
e—— -
'_ 2. NaOH, acetone, reflux
t b th
s earn a NBr
LAH. HO O O
ether,
0°C
V
O/\‘\ 0/1
\ PCC > \
NaOAc, RT
OH 0 H

 

 

26

 

brominai
bmmobU'

treated b _\

10X)')-2-,

 

OH

 

 

lEdUCtionSf

diisobmyla

4-(3-Buten-l-oxy)-2-methoxybenzonitrile (CN-OCH3) was prepared by
brornination53 of 3-methoxyphenol in acetonitrile followed by alkylation using 4-
bromobutene with potassium carbonate in refluxing acetone. The resulting product was
treated by copper cyanide in N-methylpyrrolidone54 at 180-185 °C to produce 4-(3-buten-

l -oxy)-2-methoxybenzonitri1e.

 

 

 

Br Br
O-CHa NBS O-CHa NBr O-CH3
> >
CHacN- RT Potassium Carbonate
Acetone, Reflux /
OH CH
CN
O-CHa CuCN 160-165°c

t

 

N-methylpyrrolidone

    

 

4-(3-Buten-1-oxy)-2-methoxybenzaldehyde (Al-OCHB) was prepared by

reduction” of the cyano group of 4-(3-buten-1-oxy)—2-methoxybenzonitrile using

diisobutylaluminium hydride (DIBAH) in hexane at —78 °C.

27

 

NE

 

4-
3-meth0x
potassium
buten- 1-0

180185:

 

—-—-

 

 

 

9H3

9H3
0 O
DIBAH H\
.5004; - .4}ch
Hexane, -78°C 0”

 

Al-OCH3

 

 

4-(3-Buten-1-oxy)-2-fluorobenzaldehyde (Al-F) was prepared by bromination of
3-methoxyphenol in acetonitrile followed by alkylation using 4-bromobutene with
potassium carbonate in acetone while refluxing. The resulting product, 1-bromo-4-(3-
buten-l-oxy)-2-fluorobenzene, was treated by copper cyanide in N-methylpyrrolidone at
180-185 °C to replace the bromine atom with a cyano group. The resulting product, 4-(3—
buten-1-oxy)-2-fluorobenzonitrile, was reduced with diisobutylaluminium hydride

(DIBAH) in hexane at —70 °C to afford Al-F.

 

 

 

 

 

Br Br
> ’
CH3CNv RT potassium carbonate /
OH acetone, reflux
OH O
O H CN
F F CuCN 180-185°C
‘ DIBAH ‘ .
/ hexane, .70 °C / N-methylpyrrolldone
Al-F

 

 

28

bromine:
bromobu
lbmmo

N-meth)l

 

OH

 

 

 

4-(3-Buten-1-oxy)-2-trifluoromethylbenzonitrile (CN-CF3) was prepared by
bromination56 of 3-trifluoromethylphenol in acetonitrile followed by alkylation using 4-
bromobutene with potassium carbonate in acetone while refluxing. The resulting product,
1-bromo—4-(3-buten-1-oxy)~2-trifluoromethylbenzene, was treated by copper cyanide in

N-methylpyrrolidone at 180-185 °C to give CN-CF3.

 

 

 

Bf Bf
E P/CF" NBS CFa NBr : /CF3
> >
CH3CN potassium carbonate /
acetone, reflux
0“ OH OJ
CN

CF3 CuCN 180-185°C
‘

of

 

N-methyipyrroiidone

 

 

4-(3-Buten-1-oxy)—2—trifluoromethylbenzaldehyde (Al-CF3) was prepared by
reduction of cyano group of CN-CF3 using diisobutylaluminium hydride (DIBAH) in

hexane at -78 °C.

29

 

 

4
anion)l;
methylsi

then trea

 

amnfi,
nmow,
resuitir
inrefiu:
add“;
MH031

Chlond

 

 

F30
DIBAH H\
Eager;- - 434;.
hexane, -78°C 0”

 

 

4-(3-Buten-l-oxy)-2-methylbenzonitrile (CN-CH3) was prepared by

sulfonylation of carboxylic acid of 4—buten-l’-oxy-2-methylbenzoic acid with

methylsulfonyl chloride (MSC) in pyridine followed by saturation with ammonia gas and

then treatment again with methylsulfonyl chloride (MSC) to give CN-CH3.

0\ 1. pyridine, MSC, RT

\ .

c o/—\= 2 NH3. RT > N50 Of—\=
Ho/ 3. MSC. 0 °C

CN-CH3

 

 

 

 

4—(3-Buten-1-oxy)—2—trifluoromethylbenzonitrile (CN-F) was prepared by
esterification of 3-fluorophenol with acetyl chloride in pyridine and benzene at 0°C
followed by Fries rearrangement with aluminium chloride in nitrobenzene at 0°C. The
resulting phenol was alkylated using 4-bromobutene with potassium carbonate
inrefluxing acetone followed by oxidation of the acetyl group with iodine. The carboxylic
acid, 4-buten-1’-oxy-2-methylbenzoic acid, was sulfonated with MSC in pyridine

followed by saturation with ammonia gas and then treating again with methyl sulfonyl

chloride (MSC) again to give CN-F.

3O

 

o
’U‘CH3

 

 

 

 

OH 0 OH
acetyl chloride, pyridine aluminium chloride
» a
benzene, 0°C F F
0 CH3
BTW I
o/I 0’1 O/\‘\
\ . .
\ 1. pyridine, MSC, RT ¢1-|2/pyndme.RT \
‘2. NH RT F 2. NaOH,
F 3' ,, steam bath F
CN 3. MSC, 0 C
0 0“ 0 CH3
CN-F

 

 

31

methox

follow

acetonn

 

 

mOl
met
The

4t

6-(3-Buten-l-oxy)-1-tetralone (TT) was prepared by demethylation of
methoxytetralone using sodium cyanide in dimethyl sulfoxide (DMSO) at 180 °C
followed by alkylation using 4-bromobutene with potassium carbonate in refluxing

acetone.

 

 

o
$
“o’CHa omso, 160 °c OH

 

\ 4
.0 potassium carbonate
0 acetone, reflux

 

 

2,3-Dihydro-7-(3-buten-l-oxy)-4H-benzopyran-4-one (CR) was prepared by
monoalkylation57 of resorcinol using a refluxing mixture of acrylonitrile and sodium
methoxide. Cyclization58 was then done using an acetic acid-sulfuric acid-water mixture.
The resulting product, 2,3—dihydro—7-hydroxy-4H-benzopyran-4—one, was alkylated using

4—bromobutene with potassium carbonate in refluxing acetone to give CR.

32

 

 

acetic acid,
sulfuric acid,
H20

0
("D h «N5
O O potassium carbonate 0

acetone, reflux

 

CR

 

33

 

O acrylonitrile/NaOCH3 NC
>
refl x I O
HO OH " 0 OH

reflux

OH

 

2.3. Phi

 

//

Oi

 

‘

A
in NMR 1
pressure )
PM) Was
hOUI’s of i
several pl

phOTOprOC

 

and mad,
Pyrex filte
aldehlde ;
immediate

fonowed t

Th
S‘m‘i‘hyla

2.3. Photochemistry of 4-(3-buten-l-oxy)-2-methylbenzaldehyde (Al-CH3)

6
H /——\= hv, pyrex 10 +
O acetonitrile HT’ H o
o ’

O 3 2

 

 

 

Ai-CH3 Al-CHS-COt Al-CH3-CBt

hv T

 

 

A solution of Al-CH3 (1.9 mg) in deuterated acetonitrile (0.75 mL, 1.3 x 10'2 M)

in NMR tube was purged with argon for 15 minutes and then irradiated with a medium
pressure mercury arc lamp through a Pyrex filter sleeve. One peak (a doublet around 6.42
ppm) was observed after 30 minutes but disappeared on prolonged irradiation. After three
hours of irradiation, NMR analysis of the reaction mixture showed the presence of
several photoproducts. Preparatory scale photolysis was carried out to isolate the
photoproducts. Al-CH3 (150 mg) was dissolved in freshly distilled acetonitrile (50 mL)
and irradiated in an immersion well with a medium pressure mercury arc lamp through a
Pyrex filter. After 7 hours of irradiation, 1H NMR showed the presence of the starting
aldehyde and its products. The reaction mixture was concentrated at reduced pressure
immediately. The reaction mixtures were isolated and purified by preparative TLC

followed by HPLC.

The photoproduct collected from HPLC at 3.5 minutes was identified as 4-formyl-

S-methyl-l 1-oxabicyclo[6.3.0]undeca—l,3,5-triene (Al-CH3-C0t) by its characteristic 1H

34

MIR. ll

ppmlH
3159401]
coupling
respecti‘
protons

1.6H1c

oxatricyt
the leli
PpmiH-l
6.37 pm
uniquen-
SUbSller:

plOIOn (H

Al
CB! sou];

 

NMR. It showed peaks corresponding to three vinyl protons: a doublet of doublets at 6.77
ppm(H-3), a quartet of doublets of doublets at 5.93 ppm(H-6) and a doublet of doublets
at 5.40(H-2). Peaks at 6.77 and 5.40 ppm are coupled to one another with 6.6 Hz
coupling constant and both are also coupled to H-8 with 1.1 and 2.2 coupling constants,
respectively. The peak at 5.93 ppm is assigned to H-6 coupled to two vicinal allylic
protons H-7a and H-7B with 8.2 and 7.5 Hz coupling constants and to the methyl with

1.6 Hz coupling constant.

A thermally unstable photoproduct in the mixture was identified as l-formyl-8-
oxatricyclo[7.2.0.09'5]undeca-2, lO-diene (Al-CH3-CBt) by its characteristic 1H NMR in
the mixture. It showed peaks corresponding to three vinyl protons: a doublet at 6.42
ppm(H-l l), a doublet at 6.37 ppm(H-lO) and multiplet at 5.62(H-3). Peaks at 6.42 and
6.37 ppm are coupled to one another with 3 Hz coupling. This AB quartet pattern
uniquely identifies angular cyclobutenes arising from cyclization toward the ring
substituent. The peak at 5.62 ppm is assigned to H-10 next to the methyl group. That

proton (H-10) coupled to two vicinal allylic protons H-40t, H413 and the methyl group.

Al-CHB-COt turned into Al-CHB-CBt upon prolonged irradiation but Al-CH3-

CBt could not be isolated due to its thermal instability.

35

 

 

 

 

hi—rkr»LPL

 

m . m m . m
[FF h n b P h h h L » lb b bl L— blip
z. .. .\ 3.....125. ,

 

 

a a
b tr _ H b h P by b b L?
11 JJ
_
_
m
60.202
N n o
o
9 x
o
m a. e

:UQU 5 50610-2? 122 I.

 

36

 

T H n n v m e p a m 3 a

_.p-pprpp—uppr—ppp»—r.bp—P-nhrrrup—.~.P—pbr._r->~—»nhP

 

 

 

m E __
«molar—0.2 9.6.2
2 :0 o
s O... I 1 5.0.5588 0
fl: x95 .2. illi/IK I
o m .
26.104426 222822.4—

 

 

 

37

 

 

 

 

 

 

 

 

 

 

Ea H a n v m e 4. m m
h . p p — F — _ p r F b p p p h L p h H — w . r _ r _ L t _ . r — . s r .
fillj}, b. 112.1.{411245 11.1.. ted—“tillJmllla Willi“), .111 .3
m6 6.... o.» be
L h — p h r _ — P b b _ Li bl» bLllP b P » Lib FLIL
11.x, ...\ 5.511).). i... ‘4 . (.51 19:5]. \1

. .. m t... 2. .. ..._.

g: a 2.. Z 3
n _
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m
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. .68 5 50-26-25 ”.22 2.

 

 

36

 

T. H N n G

.-p>—>-P—.Pb-—Lnr>—pnb>

 

 

 

 

 

m w h o a o." «

~p>pp—TPP-—..pwabhy—P»>k—HHHL11

 

_
m a. 2

535.2 962

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a. O... I ikmdfigceoom 0

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o m .
wig—«Co flair—.22...

 

37

2.4. Pho

 

 

 

is

M) in ar
medium
irradiati
PhOtolys

methox:

 

311d ifra
mefi
preSSUre

Wilfred

2.4. Photochemistry of 4-(3-buten-1-oxy)-2-methoxybenzaldehyde (Al-OCH3)

 

H O/_'\= hv, pyrex

acetonitrile,RT

 

 

Al-OCH3 AI-OCHS-CHa

 

 

A solution of Al-OCH3 (2.2 mg) in deuterated acetonitrile (0.75 mL, 1.41 x 10'2
M) in an NMR tube was purged with argon for 15 minutes and then irradiated with a
medium pressure mercury arc lamp through a Pyrex filter sleeve. After four hours of
irradiation, several photoproducts were observed by 1H NMR. Preparatory scale
photolysis was carried out to isolate the photoproducts. 4-(3-Buten-l-oxy)-2-
methoxybenzaldehyde (135 mg) was dissolved in freshly distilled acetonitrile (50 mL)
and irradiated in an immersion well with a medium pressure mercury arc lamp through a
Pyrex filter. After 8 hours of irradiation, the reaction mixture was concentrated at reduced
pressure. 1H NMR showed the single product. The reaction mixtures were isolated and

purified by silica gel chromatography followed by HPLC.

The photoproduct was identified as 3-formyl-4-methoxy-1l-oxatricyclo[6.3.0.0"6]
undeca—2,4—diene (Al-CHSO-CHa) by its characteristic 1H NMR in the mixture. It
showed peaks corresponding to two vinyl protons: a doublet of doublets at 6.78 ppm(H-

5) and a broad singlet at 4.66 ppm(H-Z). The peak at 4.66 ppm is assigned to a proton on

38

CTlO

pro

enol ether based on its upfield shift. The peak at 6.78 was coupled to bridgehead

proton(H—6) with 5.37 Hz; a typical coupling constant value for this system.

39

 

p—
—

 

 

 

 

 

 

«106100-?

a
memo

o z
2 o a 0
f0

3090 E «20.22001? .8 .522 I.

 

40

 

 

 

 

NMR t
prESSUI
NMR ;

phOlOI

Watt

2.5. Photochemistry of 4-(3-buten-l-oxy)-2-fluorobenzaldehyde (Al-F)

 

     

 

 

6
F 5 8 9
H F “I 6 5
/—\__ hv, pyrex ' O 10
O acetonitrile HT> H . J 7 + 0
0 ' Y 0 2
o 11 10 H F
A”: Al-F-CBt AI-F-COa

 

 

A solution of Al-F (2.1 mg) in deuterated acetonitrile (0.75 mL, 1.44 x 10'2 M) in

NMR tube was purged with argon for 15 minutes and then irradiated with a medium
pressure mercury arc lamp through a Pyrex filter sleeve. After 30 minutes of irradiation,
NMR analysis of the reaction mixture was showed the presence of two major
photoproducts. After 2 hours of irradiation, only one remained with several minor
products. Preparatory scale photolysis was carried out to isolate the photoproducts. Al-F
(160 mg) was dissolved in freshly distilled acetonitrile (50 mL) and irradiated in an
immersion well with a medium pressure mercury arc lamp through a Pyrex filter. After 1
hour of irradiation, the reaction mixture was concentrated at reduced pressure. 1H NMR
showed the presence of the starting aldehyde and its products. The reaction mixture was

isolated and purified by preparative TLC followed by HPLC.

41

charactt

iormylc

ofdoub
5.40111-
coupling
coupling
with 65

10.44 H

 

 

fonnyl-
it mi:
3.1.2) do
and 5,5
10) is c

the “lit

One photoproduct collected at 9.5 minutes from HPLC was identified as 4-
formyl-3-fluoro-l l-oxabicyclo[6.3.0]undeca—1,3,5-triene (Al-F-COa) by its
characteristic 1H NMR. It showed peaks corresponding to three vinyl protons: a doublet
of doublets at 6.15 ppm(H-S), a doublet of triplets at 5.89 ppm(H-6) and a doublet at
5.40(H-2). Peaks at 6.15 and 5.89 ppm are coupled to one another with a 12.6 Hz
coupling constant and the peak at 6.15 ppm(H-S) is coupled to fluorine with a 4.4 Hz
coupling constant. The peak at 5.89 ppm coupled to the two vicinal allylic protons H—7
with a 5.49 Hz coupling constant. The peak at 5.4 ppm (H-2) coupled to fluorine with a

10.44 Hz coupling constant.

Another photoproduct collected at 6.5 minutes from HPLC was identified as 4-
formyl-2-fluoro-l 1-oxabicyclo[6.3.0]undeca-1,3,5-triene (Al-F-COt) by its characteristic
1H NMR. It showed peaks corresponding to three vinyl protons: a doublet at 7.08 ppm(H-
3), a doublet of triplets at 5.76 ppm(H-6) and multiplet at 5.57 ppm(H-2). Peaks at 7.08
and 5.57 ppm are coupled to one another with ~7 Hz coupling. The peak at 5.76 ppm (H-
10) is coupled to the two vicinal allylic protons (H-4) with 6.59 Hz coupling constant and

the fluorine atom with a 23.07 coupling constant.

42

 

 

 

 

 

 

 

111.11
Mm.
m
59...:
N n o
o
o. I
a u.
m a o

58 5 .84? Co :22 :.

 

 

43

 

 

 

 

«009+?

 

 

:08 s 5042 .3 x22 :.

 

 

2.5.1.

F-CO

w'm

lhn

PM

due

0X

Sh

2.5.1. Irradiation of 4-formyl-2-fluoro-ll-oxabicyclo[6.3.0]undeca-l,3,5-triene (Al-

F-COt).

 

 

 

 

6
F 8 9 h
H 10 v >
0 003CN
0 3 2
Al-F-COt

Al-F-CBt

 

 

A solution of Al-F-COt (2.0 mg) in deuterated acetonitrile (0.75 mL) was purged
with argon for 15 minutes and then irradiated with a medium pressure mercury arc lamp
through a Pyrex filter sleeve. After 30 minutes of irradiation, NMR analysis of the
reaction mixture showed the presence of one photoproduct. The product was not isolated

due to thermal instability and was one of the products in NMR scale reaction.

The thermally unstable photoproduct was identified as l-formyl-2-fluoro—8-
oxatricyclo[7.2.0.09’5]undeca-2,lO-diene (AI-F-CBt) by its characteristic ‘H NMR. It
showed peaks corresponding to three vinyl protons: a triplet at 6.45 ppm(H-l l), a
doublet at 6.39 ppm(H-lO) and a doublet of doublet of doublets at 5.44(H-3). Peaks at
6.45 and 6.39 ppm are coupled to one another with a 2.75 Hz coupling constant and the

peak at 6.45 ppm (H-S) is coupled to fluorine with ~2.75 Hz coupling constant. The peak

45

Al?

at 5.44 ppm is coupled to two vicinal allylic protons H-4a, H-4B with 6.04 and 3.85 Hz

coupling constants, respectively and fluorine with a 15.93 Hz coupling constant.

In an NMR scale reaction, AI-F-CBt and Al-F-COt were formed in 2:1 ratio and

Al-F—COa and Al-F-COt were formed in a 1:2.68 ratio in a preparatory scale reaction.

46

 

 

 

 

 

 

2 : m

.m0-n_._< u4<

O
lE.c.s_cc.8c o
4 x85 .2. ”/I.\ I
m

..:< ac 225522..

or :0

 

 

47

 

 

 

in NM]
pressm
NMR

Aim 1
Conve
photo

ream

COt
21 d0!

PDm

Prov

2.6. Photochemistry of 4-(3-buten-l-oxy)-2-trifluoromethylbenzaldehyde (Al-CF3)

 

F30

H OF—\= hv, pyrex

O acetonitrile,RT

 

A"CF3 AI-CFS-CBt

 

 

A solution of Al-CF3 (2.0 mg) in deuterated acetonitrile (0.75 mL, 1.1 x 10'2 M)

in NMR tube was purged with argon for 15 minutes and then irradiated with a medium
pressure mercury arc lamp through a Pyrex filter sleeve. After 30 minutes of irradiation,
NMR analysis of the reaction mixture showed the presence of several photoproducts.
After 2 hours the reaction was complete. The major product was thermally unstable and
converted to another product, which obsorbes UV light at 317 nm. Preparatory scale
photolysis was carried out to isolate the photoproducts with 50 mg of Al-CF3. The

reaction mixture was isolated and purified by preparative TLC followed by HPLC.

The photoproduct collected at 13 minutes from HPLC was identified as Al-CF3-
COt by its characteristic 1H NMR. It showed peaks corresponding to three vinyl protons:
a doublet at 5.52 ppm(H-Z), a doublet of doublets at 6.90 ppm(H-6) and a doublet at 7.14
ppm(H—3). The peaks at 7.14 and 5.52 ppm are coupled to one another with a 6.3 Hz
coupling constant and the large upfield shift of proton H-2 is indicative of an enol ether
proton. The peak at 7.14 ppm(H-3) is coupled to the two vicinal allylic protons(H—7) with

7.69 and 7.14 Hz coupling constatnts.

48

 

 

 

 

5068.2
N n o
o.
o one
a h o .

:80 E 50.20.: go 522 I.

 

 

49

pt

if.

C l

m

cl

at

pr

2.6.1. Irradiation of 4-formyl-2-trifluoromethyl-ll-oxabicyclo[6.3.0]undeca-l,3,5-

triene (Al-CF3.COt).

 

hv, pyrex
H O acetonitrile,RT

 

 

 

Al-CF3-COt Al-CF3-CBt

 

 

A solution of Al-CF3-C0t (2.0 mg) in deuterated acetonitrile (0.75 mL) was
purged with argon for 15 minutes and then irradiated with a medium pressure mercury
arc lamp through a Pyrex filter sleeve. After 1 hour of irradiation, NMR analysis of the

reaction mixture showed the presence of a photoproduct and starting material Al-CFB-

COt.

The thermally unstable photoproduct in the mixture was identified as l-formyl-Z-
trifluoromethyl-8-oxatricyclo[7.2.0.09'5]undeca-2,lO-diene (Al-CF3-CBt) by its
characteristic 1H NMR. It showed peaks corresponding to three vinyl protons: a doublet
at 6.43 ppm(H-l 1), a doublet at 6.51 ppm(H-lO) and a multiplet at 6.82 ppm(H-3). The
peaks at 6.43 and 6.51 ppm are coupled to one another with a 2.75 Hz coupling constant
and the peak 6.82 ppm(H-3) is coupled to three fluorine atoms and two vicinal allylic

protons H-4.

50

 

 

 

 

 

 

 

K.—

 

.mOAugx‘

2 :0

hfl....

cm

x
on...

15.95858

 

4 x25 .2.

 

9.0.2

0
II CIA NYIA
Il/l|\ I
on“.

 

51

2.7. Photochemistry of 4-(3-buten-1-oxy)-2-methylbenzonitrile (CN-CH3)

 

 

CN-CH3 CN-CHa-COa CN-CHS-CBt

 

 

A solution of CN-CH3 (2.0 mg) in deuterated acetonitrile (0.75 mL, 1.43 x 10'2
M) in an NMR tube was purged with argon for 15 minutes and then irradiated with a
medium pressure mercury arc lamp through a Pyrex filter sleeve. After 14 days of
irradiation, NMR analysis of the reaction mixture showed the presence of several

photoproducts with very low conversion.

A quartz test tube containing a solution of CN-CH3 (8.0 mg) in deuterated
acetonitrile (3.0 mL, 1.43 x 10'2 M) was purged with argon for 20 minutes and then
irradiated in a Rayonet reactor with 254 nm lamps. After 18 hours of irradiation, NMR

analysis of the reaction mixture showed the presence of several photoproducts.

Another solution of CN-CH3 (2.0 mg) in deuterated acetone (0.75 mL, 1.43 x 10'
2 M) in an NMR tube was purged with argon for 15 minutes and then irradiated through a
313 nm filter solution. After 24 hours of irradiation, NMR analysis of the reaction
mixture showed the presence of several photoproducts. Preparatory scale photolysis was
carried out to isolate the photoproducts. CN-CH3 (183 mg) was dissolved in freshly

distilled acetone (50 mL) and irradiated through a 313 nm filter solution. After 16 hours

52

 

 

of irra
show:

isolatu

meth}
MIR.
abroa

5.77 a.

 

 

peak 6
consta

DIOtor

of irradiation, the reaction mixture was concentrated at reduced pressure. 1H NMR
showed the presence of the starting nitrile and its products. The reaction mixture was

isolated and purified by silica gel chromatography followed by HPLC.

One photoproduct collected at 8 minutes from HPLC was identified as 4-cyano-3-
methyl-1l-oxabicyclo[6.3.0]undeca—l,3,5-triene (CN-CH3-COa) by its characteristic 1H
NMR. It showed peaks corresponding to three vinyl protons: a singlet at 5.25 ppm(H-2),
a broad doublet at 5.77 ppm(H-S) and a doublet of triplets at 6.77 ppm(H-6). The peaks at
5.77 and 6.77 ppm are coupled to one another with a 13 Hz coupling constant and the
peak 6.77 ppm(H-6) is coupled to two vicinal allylic protons H-7 with a 4.4 Hz coupling
constatnt. The large upfield shift of proton H-2 at 5.25 ppm is indicative of an enol ether

proton.

Another photoproduct collected at 3 minutes from HPLC was identified as l-
cyano-2-methyl-8-oxatricyclo[7.2.0.09'5]undeca-2,lO-diene (CN-CHS-CBt) by its
characteristic IH NMR. It showed peaks corresponding to three vinyl protons: a doublet
at 6.77 ppm(H-IO), a doublet at 6.17 ppm(H-l 1) and a quartet of triplets at 5.48 ppm(H-
3). The peaks at 6.77 and 6.17 ppm are coupled to one another with a 2.8 Hz coupling
constants. The peak at 5.48 ppm(H-3) is coupled to two vicinal allylic protons H-4 with a

6.04 Hz coupling constant and the methyl group with a 1.65 Hz coupling constant.

The CN-CH3-COa/ CN-CHB-CBt ratios were measured by NMR analysis to be

1:2, 5:1 and 3:1 with the light sources of >300 nm, 254 nm and 313 nm, respectively.

53

Dune

dong

 

 

Dimerization between the double bond of the butenyl tether and acetone was observed

along with dimerzation between acetones by ‘H NMR, 13c NMR, DEPT, IR and MS.

54

 

 

 

 

 

 

 

 

 

m00.95.20

 

2050 E «00.2.5.va .3 £22 :.

 

55

 

 

 

 

 

v m w b
_ . p _ r _ . . > — > . p L p w L

.119. .l 4. ..H. (11. ltlwll

; n 2

 

 

ion w.m Ntw
Lb—Fbpp~hhp_—>L Err.

( gjfil

 

 

 

 

 

 

: 2 60.96.20 _.
2 : ‘
o... 02 _

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on

 

 

2090 E .mutmzotzu .3 .522 I.

 

56

23.1

NC

 

 

2.8. Photochemistry of 4-(3-buten-l -oxy)-2-methoxybenzonitrile (CN-OCH3)

9H3
0
NC O/—\= hv, pyrex 010 + :5...
acetonitrile, FtT>
NC
on 100

H3

 

 

CN-OCH3
CN-OCH3-COa CN-OCH3-CBt

a
10 9 7 6

£035
0

NC 3

9 2 4

CH3

CN-OCHS-LCBa

 

 

A solution of CN-OCH3 (2.7 mg) in deuterated acetonitrile (0.75 mL, 1.8 x 10'2
M) in an NMR tube was purged with argon for 15 minutes and then irradiated with a
medium pressure mercury arc lamp through a Pyrex filter sleeve. After 20 hours of
irradiation, NMR analysis of the reaction mixture showed the presence of several

photoproducts with very low conversion.

Another solution of CN-OCH3 (10.8 mg) in deuterated acetonitrile (3.0 mL, 1.8 x
10'2 M) in a quartz test tube was purged with argon for 20 minutes and then irradiated in
a Rayonet reactor with 254 nm lamps. After 18 hours of irradiation, NMR analysis of the

reaction mixture showed the presence of several photoproducts.

57

throu
react

phott

 

dissol

soluti

presu

reacti

Another solution of CN-OCH3 (2.7 mg) in deuterated acetone (0.75 mL, 1.8 x
10’2 M) in an NMR tube was purged with argon for 15 minutes and then irradiated
through a 313 nm filter solution. After 30 hours of irradiation, NMR analysis of the
reaction mixture showed the presence of three photoproducts. Preparatory scale
photolysis was carried out to isolate the photoproducts. CN-OCH3 ( 177 mg) was
dissolved in freshly distilled acetone (50 mL) and irradiated through a 313 nm filter
solution. After 28 hours of irradiation, the reaction mixture was concentrated at reduced
pressure. 1H NMR showed the presence of the starting nitrile and its products. The

reaction mixture was isolated and purified by preparative TLC followed by HPLC.

Two products eluted after at 9 minutes of HPLC. one photoproduct was isolated
and identified as 4-cyano—3-methoxy-11-oxabicyclo[6.3.0]undeca-1,3,5-triene (CN-
OCH3-C0a) by its characteristic 1H NMR while the other product was identified in the
mixture. It showed peaks corresponding to three vinyl protons: a singlet at 5.32 ppm(H-
2), a doublet of triplets at 5.75 ppm(H-6) and a doublet of triplets at 5.83 ppm(H-S). The
peaks at 5.75 and 5.83 ppm are coupled to one another with ~12 Hz coupling constant
and the peak at 5.75 ppm(H-6) is coupled to the two vicinal allylic protons H-7 with 4.4
Hz coupling constatnt. The large upfield shift of proton H-2 at 5.32 ppm is indicative of

an enol ether proton.
The other photoproduct to elute after 9 minutes was identified as ll-cyano-l-

methoxy-4-oxatricyclo[7.2.0.03’7]undeca—2,10-diene (CN-OCH3-LCBa) by its

characteristic 1H NMR. It showed peaks corresponding to two vinyl protons: a singlet at

58

 

 

4.92
4.93

alhl‘.

idem
CBts
a dou
4.65 r

Hzco

 

andH

 

Ofant

mfifsu

313 nr

4.92 ppm(H-2) and a doublet at 6.9 ppm(H-lO). The large upfield shift of proton H-2 at
4.92 ppm is indicative of an enol ether proton. The proton H-lO at 6.9 ppm coupled to the

allylic proton H-9 with a 1 Hz coupling constant that is typical value for this structure.

Another photoproduct collected at 6 minutes was not stable thermally and
identified as 1-cyano-2-methoxy-8-oxatricyclo[7.2.0.095]undeca-2,10-diene (CN-OCH3-
CBt) by its characteristic 1H NMR. It showed peaks corresponding to three vinyl protons:
a doublet at 6.29 ppm(H-lO), a doublet at 6.18 ppm(H-l 1) and a doublet of doublets at
4.65 ppm(H-3). The peaks at 6.29 and 6.18 ppm are coupled to one another with a 2.75
Hz coupling. The peak at 4.65 ppm(H-3) coupled to the two vicinal allylic protons H40
and H-4B with 6.59 and 2.8 Hz coupling constants and its lager upfield shift is indicative

of an enol ether proton.

The ratios of CN-OCH3—C0a: CN-OCH3-CBt: CN-OCHB-LCBa were
measured by NMR analysis to be 8: 2: 1 and 10: 1 :1 with the light sources of 254 nm and

313 nm, respectively.

59

 

 

 

 

 

 

 

 

 

 

 

 

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press
NMF

Very

M) .
Solu
the
isol
diss
501‘
Pre
tea

HP

2.9. Photochemistry of 4-(3-buten-1-oxy)-2-fluorobenzonitrile (CN-F)

F
hv, ex
NC O/_\= p yr >
acetomtnlefiT

CN'F CN-F—CBt CN-F—CBa

 

 

 

 

 

A solution of CN-F (2.0 mg) in deuterated acetonitrile (0.75 mL, 1.39 x 10'2 M)

in an NMR tube was purged with argon for 15 minutes and then irradiated with a medium
pressure mercury arc lamp through a Pyrex filter sleeve. After 14 days of irradiation,
NMR analysis of the reaction mixture showed the presence of several photoproducts with

very low conversion.

Another solution of CN-F (2.0 mg) in deuterated acetone (0.75 mL, 1.39 x 10'2
M) was purged with argon for 15 minutes and then irradiated through a 313 nm filter
solution. After 24 hours of irradiation, NMR analysis of the reaction mixture was showed
the presence of several photoproducts. Preparatory scale photolysis was carried out to
isolate the photoproducts. 4-(3-Buten-l-oxy)-2-fluorobenzonitrile (166 mg) was
dissolved in freshly distilled acetone (50 mL) and irradiated through a 313 nm filter
solution. After 48 hours of irradiation, the reaction mixture was concentrated at reduced
pressure. 1H NMR showed the presence of the starting nitrile and its products. The
reaction mixture was isolated and purified by silica gel chromatography followed by

HPLC.

63

 

cym

 

char

316

i3}

Hzc

 

coup.
1140

“lfll

Cyan
char
315.
doul
9.89
4a 2
lite

COn

The photoproduct collected off the HPLC at 9.5 minutes was identified as 1-
cyano-2-fluoro-8-oxatricyclo[7.2.0.09’5]undeca—2,10—diene (CN-F-CBt) by its
characteristic lH NMR. It showed peaks corresponding to three vinyl protons: a doublet
at 6.25 ppm(H-l 1), a doublet at 6.33 ppm(H-lO) and a doublet of doublets of doublets at
5.33 ppm(H-3). The peaks at 6.25 and 6.33 ppm are coupled to one another with a 2.75
Hz coupling and the peak at 6.33 ppm is coupled to the fluorine atom with ~3 Hz
coupling constant. The peak 5.33 ppm(H-3) is coupled to the two vicinal allylic protons
H-4a and H46 with 8.24 and 3.3 Hz coupling constants and also coupled to fluorine

with a 15.38 Hz coupling constant.

Another photoproduct collected off the HPLC at 5.5 minutes was identified as 1-
cyanol1-fluoro-8-oxatricyclo[7.2.0.09'5]undeca-2,10-diene (CN-F-CBa) by its
characteristic 1H NMR. It showed peaks corresponding to three vinyl protons: a doublet
at 5.11 ppm(H-lO), a doublet of doublets at 5.72 ppm(H-2) and a doublet of doublet of
doublets at 5.93 ppm(H-3). Peaks at 5.72 and 5.93 ppm are coupled to one another with a
9.89 Hz coupling. The peak at 5.72 ppm(H-2) is coupled to the vicinal allylic proton H-
4a and the peak at 5.93 ppm is coupled to the two vicinal allylic protons H-4a and H-4B.
The peak at 5.11 ppm(H-lO) is coupled to a fluorine atom with a 8.79 Hz coupling

constant .

The ratios of CN-F—CBt: CN-F—CBa were measured by NMR analysis to be 1.6:

1 and 1: 1.8 ratio with the light sources of >300 nm and 313 nm, respectively.

 

 

 

11

n.m

v..."

prkprr'r

if!

 

 

 

o—

 

 

 

 

 

50.“.-20

or F...

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2000 5 501-20 0.. x22 :.

 

65

 

 

 

v m

n n > .F —

o.m Non
—__»n»~»..L»I

1.2),. \ll

 

 

c—

 

b

b

L

o h

h h 1». F u h in h

 

Jalfil . I

o.m o.»

»I_»>pb.»».__»»»—lpl

80.420
2 a

40... 02
. I. N

a
cm

2000 E «m0-n_-ZU.Io «22 I.

 

 

 

 

flue
Witt
Aft:
pm.
the
diet

7.2

 

 

 

254 / rtz 1° 9 8 7 6
ms fl= W » ms
acetomtnleRT NC F 3 o

2 4

CN-F CN-F—LCBa

 

 

A quartz test tube containing another solution of 4—(3-buten-l-oxy)—2-
fluorobenzonitrile (8.0 mg) in deuterated acetonitrile (3.0 mL, 1.39 x 10'2 M) was purged
with argon for 15 minutes and then irradiated in a Rayonet reactor with 254 nm lamps.
After 30 hours of irradiation, NMR analysis of the reaction mixture was showed the
presence of several photoproducts. After 60 hours of irradiation, one of the products in
the mixture was assigned as 1 l-cyano-l-fluoro.4-oxatricyclo[7.2.0.03 '7]undeca-2,10-
diene (CN-F-LCBa) based on the characteristic two vinylic peaks at 4.96 ppm (H-2) and

7.23 ppm (H-10).

67

 

 

 

30...-u20

 

02 565.528..

 

E0303: «mm

o—

0.20

8010102
“I

 

 

68

2.9.1. Thermal chemistry of 1-cyano-2-fluoro-8-oxatricyclo[7 2.0.05”s ]undeca-2,10-

diene (CN-F-CBt)

 

 

9
00300 F 3
I» 1 0

CN-F-CBt CN-F-COI

 

 

 

A solution of CN-F-CBt (1.1 mg) in deuterated methanol (1 mL) was purged with
argon and heated in a constant temperature bath at 80 °C. The reaction progress was
monitored by HPLC and 1H NMR. After 12 hours of heating, a single product was

formed.

The product was identified as 4-cyano-5-fluoro-11-oxabicyclo[6.3.0]undeca-
1,3,5-triene (CN-F-COt) by its characteristic 1H NMR. It showed peaks corresponding to
three vinyl protons: a doublet at 5.40 ppm(H-2), a doublet of triplets at 5.70 ppm(H-6)
and a doublet at 6.86 ppm(H-3). The peaks at 5.40 and 6.86 ppm are coupled to one
another with a 7.32 Hz coupling. The peak at 5.70 ppm(H-6) is coupled to two vicinal
allylic protons H-7 with a 5.86 Hz coupling constant and coupled to fluorine with a 23.93

Hz coupling constant.

69

 

 

h h h — h F F b

7......IIIJ

 

 

O 02
o u.
m s o
Donn—0 5 501.20 .3 £22 I.

 

70

diet

wi‘

pn

2.9.2. Thermal chemistry of l-cyano-l1-fluoro-8-oxatricyclo[7.2.0.0"]undeca-2,10-

diene (CN-F-CBa)

 

 

 

 

A solution of CN-F-CBa (2.2 mg) in deuterated methanol (1 mL) was purged

with argon and heated in a constant temperature bath at 50 °C. The reaction progress was
monitored by HPLC and 1H NMR. After 24 hours of heating, a single product was

produced. Same result was observed after heating at 80 °C for 6 hours.

The photoproduct was identified as 4-cyano-3-fluoro-1 l-
oxabicyclo[6.3.0]undeca-1,3,5-triene (CN-F-COa) by its characteristic lH NMR. It
showed peaks corresponding to three vinyl protons: a doublet at 5.31 ppm(H-2), a
doublet of doublets at 5.76 ppm(H-S) and a doublet of triplets at 5.98 ppm(H-6). Peaks at
5.76(H-5) and 5.98(H-6) ppm were coupled to one another with a 12.64 Hz coupling. The
peak at 5.76(H-5) is coupled to fluorine atom with a 4.94 Hz coupling constant and the
peak at 5.98(H-6) ppm is coupled to the two vicinal allylic proton H-7 with a 5.49 Hz
coupling. The peak at 5 .31 ppm(H-2) coupled to fluorine with a 9.34 Hz coupling
constant and its large upfield shift is indicative of an enol ether proton. Irradiation of CN-

F-COt and CN-F-COa gave only trace of corresponding CB.

71

 

 

 

 

8320

or

 

0050 E 000-m-20 00 522 I.

hcm o.n 0.0
P . p b . h I p r p I .
I ) .. tJ.. . . :
I...._..,.\._a .I. III ...I. _.._.I..IIII.
I... III... IIII...::I
.3 II _II. .I .

: ._ _ .I_

_

.I I

_

 

72

2.10. Photochemistry of 4-(3-buten-l-oxy)-2-trifluorofluoromethylbenzonitrile (CN-

CF 3)

 

 

 

 

8
F3C 5 6 ””97 6
O. 5
NC O/——\:- hv, pyrex > ., J 7 + NC 3 O
acetonltnle,FtT F30 2 4
CN-CFS CN-CF3-CBt CN-CFS-LCBa

 

 

A solution of CN-CF3 (2.1 mg) in deuterated acetonitrile (0.75 mL, 1.16 x 10'2

M) was purged with argon for 15 minutes and then irradiated with a medium pressure
mercury arc lamp through a Pyrex filter sleeve. After 36 hours of irradiation, NMR
analysis of the reaction mixture showed the presence of several products on the complete

depletion of the reactant.

A quartz test tube contains another solution of CN-CF3 (8.4 mg) in deuterated
acetonitrile (3.0 mL, 1.16 x 10'2 M) was purged with argon for 15 minutes and then
irradiated in a Rayonet reactor with 254 nm lamps. After 12 hours of irradiation, NMR
analysis of the reaction mixture showed the presence of several photoproducts on the
complete depletion of the reactant. The major product was identical to one of the

products observed with irradiation of >300 nm.

Another solution of CN-CF3 (2.0 mg) in deuterated acetone (0.75 mL, 1.5 x 10'2

M) was purged with argon for 15 minutes and then irradiated through a 313 nm filter

73

solution. After 22 hours of irradiation, NMR analysis of the reaction mixture showed the
presence of two photoproducts. Preparatory scale photolysis was carried out to isolate the
photoproducts. CN-CF3 (148 mg) was dissolved in freshly distilled acetone (50 mL) and
irradiated through a 313 nm filter solution. After 24 hours of irradiation, the reaction
mixture was concentrated at reduced pressure. 1H NMR showed the presence of the
starting nitrile and its products. The reaction mixture was isolated and purified by

preparative TLC followed by HPLC.

One photoproduct collected off the HPLC at 11 minutes was identified as l-
cyano-2-trifluoromethyl-8-oxatricyclo[7.2.O.09'5]undeca-2,lO-diene (CN-CF3-CBt) by
its characteristic 1H NMR. It showed peaks corresponding to three vinyl protons: a
doublet at 6.22 ppm(H-l 1), a doublet at 6.31 ppm(H-lO) and a multiplet at 6.51 ppm(H-
3). Peaks at 6.22 and 6.31 ppm are coupled to one another with a 2.75 Hz coupling
constant. The peak a 6.51 ppm(H-3) coupled to two vicinal allylic protons H-4 and three

fluorine atoms.

The other photoproduct collected off the HPLC at 7 minutes was identified as 11-
cyano—l-trifluoromethyl-4-oxatricyclo[7.2.O.O3'7]undeca-2,lO-diene (CN-CF3-LCBa) by
its characteristic 1H NMR. It showed peaks corresponding to two vinyl protons: a singlet
at 4.93 ppm(H—Z) and a singlet at 6.94 ppm(H-lO). The large upfield shift of the proton

at 4.93 ppm(H-Z) is indicative of an enol ether proton of linear cyclobutene structure.

74

The ratios of CN-CF3-CBt: CN-CFB-LCBa were measured by NMR analysis to
be 1:10, 1:10 and 1:1 ratio with the light sources of >300 nm, 254 nm and 313 nm,

respectively.

75

 

 

 

 

 

 

 

 

an a a n e m m h
- _ — p b p P — - p P L — p P — p n — P Lr P lpl
l l. 3.!) E... 4% 153... gm
_. * 2r (0 h
0. _ ... _ m _
:
2
50.90.20
or 2
~10... oz
... n
m m. 0 u.
v n

2000 5 50.90.20 ..o «22 I.

 

76

 

PH

— if k Lr r
.

if};

 

 

N o—

804.9520

:80 E §0A-mm0.z0 .3 x22 2.

 

 

 

 

77

2.10.1. Thermal chemistry of l-cyano-2-trifluoromethyl-S-oxatricyclo[7.2.0.095]

undeca-2,10-diene (CN-CFB-CBt)

 

 

 

CN-CF3-CBt CN-CF3-COt

 

 

,-

A solution of CN-CF3-CBt (2.4 mg) in deuterated methanol (1 mL) was purged
with argon and heated in a constant temperature bath at 100 °C. The reaction progress
was monitored by HPLC and 1H NMR. After 24 hours of heating, the mixture showed a
compound absorbing UV around 320 nm and decomposed products.

The photoproduct was identified as 4-cyano-5-trifluoromethyl-l l-oxabicyclo
[6.3.0]undeca-l,3,5-triene (CN-CFS-COt) by its characteristic IH NMR. It showed peaks
corresponding to three vinyl protons: a doublet at 5.16 ppm(H-Z), a triplet at 6.41
ppm(H-6) and a doublet at 6.54 ppm(H—3). Peaks at 5.16 and 6.54 ppm are coupled to one
another with a 6.59 Hz coupling. The peak at 6.41 ppm(H-6) coupled to the two vicinal

allylic protons H-7 with a 7.69 Hz coupling.

78

2.11. Photochemistry of 6-(3-Buten-1-oxy)-1-tetralone ('l'l‘)

 

 

.0 O/—\= hv, pyrex >
O acetonitrile,RT

 

 

 

A solution of TT (2.1 mg) in deuterated acetonitrile (0.75 mL, 1.29 x 10'2 M)

was purged with argon for 15 minutes and then irradiated with a medium pressure
mercury arc lamp through a Pyrex filter sleeve. After 8 hours of irradiation, NMR
analysis of the reaction mixture showed the presence of several photoproducts.
Preparatory scale photolysis was carried out to isolate the photoproducts. TT (182 mg)
was dissolved in freshly distilled acetonitrile (50 mL) and irradiated with a medium
pressure mercury arc lamp through a Pyrex filter sleeve. After 8 hours of irradiation, the
reaction mixture was concentrated at reduced pressure. 1H NMR showed the presence of
the starting ketone and its products. The reaction mixture was isolated and purified by

preparative TLC followed by HPLC.

79

One photoproduct collected off the HPLC at 13 minutes was identified as 15-oxa-
tetracyclo[10, 3, 0, 01's, 03’8]pentadeca-2,9-diene-7-one (TT-CBa) by its characteristic 1H
NMR. It showed peaks corresponding to three vinyl protons: a doublet of doublets at 5.69
ppm(H-9), a doublet at 5.83 ppm(H-2) and a doublet of doublet of doublets at 5.96
ppm(H-lO). Peaks at 5.69(H-9) and 5.96 ppm(H-lO) are coupled to one another with a
9.9 Hz coupling constant and the peak at 5.96 ppm(H-lO) is coupled to two vicinal allylic
protons H-ll with a coupling constant of 6.9 Hz and 1.8 Hz. The peak at 5.83 ppm(H-2)

is coupled to allylic proton H-40t with a 2.1 Hz coupling constant.

Another photoproduct collected off the HPLC at 10 minutes was identified as 15-
oxa—tricyclo[ 10, 3, O, 03’8]pentadeca-l, 3, 9-triene-7-one ('IT-COa) by its characteristic
1H NMR. It showed peaks corresponding to three vinyl protons: a doublet at 6.21 ppm(H-
9), a doublet of triplets at 5.86 ppm(H-IO) and a singlet at 5.38 ppm(H-2). Peaks at 6.21
and 5.86 ppm are coupled to one another with ~12 Hz coupling constant and the peak at
5.86 ppm(H-lO) is coupled to the two vicinal allylic protons H-ll with a coupling
constant of 4.5 Hz. The large upfield shift of the proton at 5.38 ppm(H-2, singlet) is

indicative of an enol ether.
The other photoproduct collected off the HPLC at 9 minutes was identified as 15-

oxa—tetracyclo[10, 3, O, 01'"), 04’9]pentadeca-2, 4-diene-5-one (TT-CHt) by its

characteristic IH NMR. It showed peaks corresponding to two vinyl protons: a doublet at

80

5.5 ppm(H-2) and a doublet at 6.6 ppm(H-3). Two peaks were coupled to one another

with a 10 Hz coupling constant that is a typical value for this structure.

TT-CBa, 'l'F-COa and 'I'F-CHt were observed in 10:2:1 ratio.

81

 

 

 

 

 

 

an a u n v o a.
H. p _ L _ _ _ . h l
/_ . ... .. ...‘l‘ jg? N111! ill.) \1111 1
J0) 0.”... a. fix; ......“ ._ in ,3“
r. ,. T. . a“ _ _ a ., . __
.
. ...? a a. k
4.. . o _ 2
N

 

 

 

 

2000 E 50-: ..o .522 I.

 

 

 

82

 

 

 

  

up w.

5 on

.68 s 59:? x22 :.

 

 

83

 

 

 

 

m N
.xofi
2
a. o o
p
: m n

.68 5 .5?» do :22 :.

 

 

84

2.12. Photochemistry of 6-(3-huten-l-oxy)-1-Chromonone (CR)

0
0 n. m
0 acetonitrile,RT

CR

    

 

 

  

 

A solution of CR (2.1 mg) in deuterated acetonitrile (0.75 mL, 1.28 x 10'2 M)

was purged with argon for 15 minutes and then irradiated with a medium pressure
mercury arc lamp through a Pyrex filter sleeve. After 2 hours of irradiation, NMR
analysis of the reaction mixture showed the presence of several photoproducts.
Preparatory scale photolysis was carried out to isolate the photoproducts. CR (170 mg)
was dissolved in freshly distilled acetonitrile (50 mL) and irradiated through a Pyrex
filter sleeve. After 8 hours of irradiation, the reaction mixture was concentrated at
reduced pressure. 1H NMR showed the presence of the starting ketone and its products.
The reaction mixture was isolated and purified by silica gel chromatography followed by

HPLC.

One photoproduct collected off the HPLC at 22 minutes was identified as 4,15-
dioxa-tricyclo[10, 3, 0,03'8 ]pentadeca-1, 3, 9-triene-7-one (CR-COa) by its characteristic
1H NMR. It showed peaks corresponding to three vinyl protons: a singlet at 5.3 ppm(H-

2), a doublet of triplets at 5.8 ppm(H-IO) and a doublet at 6.2 ppm(H-9). Peaks at 6.2 and

85

5.8 ppm are coupled to one another with a 12.5 Hz coupling constant and the peak at 5.8
ppm(H-IO) is coupled to the two vicinal allylic protons H-7 with a coupling constant of
4.5 Hz. The large upfield shift of the proton at 5.38 ppm(H-2, singlet) is indicative of an

enol ether.

The other photoproduct collected off the HPLC at 12 minutes was identified as
8,15-dioxa-tetracyclo[10, 3, O, 0""), 04’9]pentadeca-2, 4-diene-5-one (CR-CHt) by its
characteristic 1H NMR. It showed peaks corresponding to two vinyl protons: a doublet at
5.3 ppm(H-2) and a doublet at 6.5 ppm(H-3). Two peaks were coupled to one another

with a 10 Hz coupling constant that is a typical value for the CHt structure.

Two products were identified as CR-COa and CR-CHt in 10 > 1 ratio.

86

 

 

 

 

   

/
O. .
p: o_.
n.000 5 «0005.6 :22 :_

9m

 

 

87

 

n
b b l— p b P L L h P h L P b

N v m o h

P L b — p b L- P r— L

jejjfili

N

 

 

 

 

.58 ... .236 cc azz :.

 

88

Singlet and triplet energy of reactants were measured on a fluorescence

spectrophotometer and UV-VIS spectrometer as shown in Table 6.

Table 6. Singlet and triplet energy of reactants.

 

 

 

 

 

 

S;(kcal/mol) T1(kcal/mol) S.(kca1/mol) T1(kca1/mol)
Al-CH3 96.3 67.6 CN-CH3 96.3 78.3
Al-OCH3 94.7 67.3 CN-OCH3 96.9 78.3
Al-F 97.6 69.9 CN-F 101.4 77.0
Al-CF3 98.6 66.5 CN-CF3 98.6 78. l

 

 

 

 

 

 

2.13. Computational Studies

Ab initio calculation of excited and ground states using the (U )HF/6-3 16’” method

were carried out to provide additional insight into the factors that control the

regioselectivity associated with the ortho [2+2] photocycloaddition.

Geometry optimization and energy calculations of ground states of Al-CH3, Al-

OCH3, Al-F and Al-CF3 were carried out for both conformers.

89

 

Table 7. Ground state energy of ortho substituted p-butenoxybenzaldehyde (Al-X)

 

 

 

 

 

 

Emi(kcal/mol) Esyn(kcal/mol)
Al-CH3 -384204.040 -384204.675
Al-OCH3 431171.3178 431166.181
Al-F 421739.154 421735.948
Al-CF3 -57031 1.278 -570308. 198

 

 

 

 

Geometry optimization, energies and dipole moment of excited triplet states of

Al-CHB, Al-OCH3, Al-F, and Al-CF3 were carried out for both conformers.

Table 8. Dipole moments and energy of anti/syn conformer of ortho substituted p-
butenoxybenzaldehyde(Al-X).

 

 

 

 

 

 

 

Anti conformer Syn conformer

Emfi(kcal/mol) Dipole (Debye) Esyn(kcal/mol) Dipole(Debye)
Al-CH3 -384148. 1 12 3.489 -384147.79O 4.469
Al-OCH3 431 1 14.499 4.962 431 108.415 4.924
Al-F 421683.555 4.397 421677.992 6.381
Al-CF3 -570256.652 4.846 -570254.585 7.264

 

 

 

 

 

Geometry optimization and energies of BR, CH, CO, and CB of Al-CH3, Al-

OCH3, Al-F, and Al-CF3 were carried out for both conformers and both regioisomers.

 

Part 3. Discussion

3.1. Regioselectivity

A high degree of regioselectivity was observed in photocycloaddition of ortho
substituted p-butenoxybenzaldehydes and cyclic analogues while ortho substituted p-

butenoxybenzonitrile showed relatively low degree of regioselectivity.

 

x \
X X
H o H C > H
<— 4— hv 0 hv @» —>
O o o o

X=OCH3, F (27.2%) X=CH3, CF3, F (72.8%)

 

 

Generally, in case of the benzaldehyde system, electron-withdrawing groups
direct the addition of the double bonds towards these substituents (syn-addition) while
strong electron-donating groups drives the double bond away from the substituent (anti-

addition).

 

 

x
_hv_> —> —>
0 o
x.—cH2 (92.3%), o (> 90%) X=CH2 (7.7%). O (< 10%)

 

 

91

In case of cyclic phenylketone systems, p-butenoxy tetralone ('IT) and
chromanone (CR), which are analogues of ortho methyl (Al-CH3) and methoxy (Al-
OCH3) substituted p—butenoxybenzaldehydes with anti-conformation, form regioisomers

with the double bonds adding away from the substituents (anti-addition).

 

x {>9
«HOW .2021" "CG .300... “433'”
CH3CN CH30N

X=CH3 (33-54%). OCHa (§7-1°/o). x=CI-I3 (66.7%),OCH3 (42.9%),
F (38.5 /o). CFa (>90 A) F (61.5%), CF3 (<10%)

 

 

Regioselectivity of ortho substituted p-butenoxybenzonitrile showed a
dependancy on the light source. In case of the light source over 300 nm, only CF3 group

showed a high degree of anti regioselectivity.

 

x o x \ x
<— <- NC ‘254nm C-Q—O 254""? N C —> —>
CH3CN CH3CN o
x.-CH3 (83.3%), OCH3 (81.8%), X=CH3116-7°/°). OCHa (182%)
F, CF3

 

 

92

In case of direct irradiation with 254 nm, the initial [2+2] ortho cycloaddition of

the double bond is anti to all ortho ring substituents with over 80% selectivity.

 

313nm 313nm _>
<—4— NC 4— Nc—O-o ——> NC "
acetone acetone 0

X=CH3 (75%). OCH3 (91.7%), X=CH3 (25%), OCH3 (8.3%),
F (64.3%), CF3 (50%) F (35.7%), CF3 (50%)

 

 

In case of sensitization by acetone with 313nm light source, stronger electron-

donating groups showed higher degree of regioselectivity.

A high degree of regioselectivity was observed in the photocycloaddition of ortho
substituted p—butenoxyacetophenone. In nearly all cases studied, electron-donating and
electron-withdrawing groups direct the remote double bond syn. The difference between
the two systems implies the presence of another major factor that determines
regioselectivity. In order to understand the reason for this regioselectivity, each step of

the reaction mechanism must be analyzed.

93

3.2. Overall Mechanism

Irradiation of p-butenoxybenzaldehyde derivatives generates a charge transfer
complex (exciplex; EX) that subsequently collapses to a biradical (BR). Then, the
biradical (BR) can either convert to starting material or cyclize to form cyclohexadiene

(CH).

 

 

 

Subtle electronic or steric effects at any step of initial cyclization mechanism

could have profound effect on the regioselectivity. The significance of these factors on

each step of the reactions scheme will be discussed.

Cyclohexadiene (CH) thermally opens to cyclooctatriene (CO) which can

photochemically cyclizes to either linear (LCB) or angular cyclobutene (CB). There are

94

two different modes of addition for each conformer of the two possible carbonyl

 

fOtOIIlCI‘S.
x \
H
O o
o
hv
x
x
“ ‘ “ 0°
0 QC 0 .
AI-X-CHt Al-X-CHa

l

X
I
O

H
0

 

 

 

 

 

I x
[Id
0

I
x
\
O
:I:
E
\
O
I
[Ii
0

Al-X-CBt AI-X-LCBt Al-X-LCBa Al-X-CBa

 

95

3.2.1. Formation of Exciplex

The conformational structure of the exciplex has been shown to affect
regioselectivity in the ortho photocycloaddition of 2-substituted 4-
butenoxyacetophenone. It is believed that charge transfer interactions will be stronger
with a more positive carbon center. Since there is no strong steric interaction, after
considering inductive and resonance effects of substituents to the acetyl group, it was
concluded that all studied electron-donating and electron-withdrawing groups facilitate a

syn orientation of the remote double bonds toward themselves.

 

 

   

X=CH3, oer-13, F, CF3 K>>1

 

 

Considering little difference in the structures between acetophenone and

benzaldehyde derivatives, varying regioselectivity suggests that electronic effect is not
solely responsible for the regioselectivity. It was suggested that the regioselectivity is

associated with a differentiating effect by dipole-dipole interactions on exciplex

96

formation.46 The following scheme shows the overall mechanism when the double bond

adds toward the substituents (syn addition).

 

x\ X\
Hi =2 :3»

O
Ganti
ml hv l
1
S
1 Santi syn

 

 

97

The rate of the triplet state anti—>syn rotation was measured to be ~107 in

photokinetic study of o-alkyl phenyl ketone by Wagner and Chen.59

Ab initio calculations on the ground states and excited triplet states of ortho
substituted p-butenoxybenzaldehydes were carried out. The calculation suggests that anti
conformers are more stable for the derivatives with all substituted
butenoxybenzaldehydes in the ground state as well as excited triplet state. An exception
was the mild electron-donating methyl group for which compound, syn conformer is
more stable in the ground state while syn and anti conformer are similar in energy at

excited triplet state.

Table 9. Ground state energy of ortho substituted p-butenoxybenzaldehyde (Al-X)

 

 

 

 

 

AE=Eamr Esyn (kcal/mol) Calculated Ratio(anti/syn)
Al-CH3 -0.635 25.50 : 74.50
Al-OCH3 5.137 99.98 : 0.02
Al-F 3.206 99.56 : 0.44
Al-CF3 3.080 99.45 : 0.55

 

 

 

 

 

98

Table 10. Triplet excited state energy and direction of diploe moment of ortho substituted
p-butenoxybenzaldehyde (Al-X)

 

 

 

 

 

 

Dipole (Debye), tr Dipole (Debye), u AE(kca1/mol) Calculated

of antioconformer of syn-conformer Ratio (anti/syn)
Al-CH3 0.322 50.014 I 49.986
Al-OCH3 6.084 99.996 2 0.004
Al-F 5.563 99.992 2 0.008
Al-CF3 2.067 97.037 : 2.963

 

 

 

 

 

 

 

=9 molecular dipole

—> charge transfer
dipole

 

side a side t

syn conformer
syn addition

 

 

Figure 2. Dipole interaction of ortho substituted p-butenoxybenzaldehyde (Al-X) with

syn conformer for syn addition.

100

 

 

 

 

II F
Elm

 

 

5.

8

Figure 3. Equilibria between two addition modes of ortho substituted p-

l

 

 

 

butenoxybenzaldehyde (Al-X) on exciplex state.

101

Consideration of interactions between the molecular dipole of the excited triplet
state and the charge transfer dipole can provide insight into the interactions between two
dipoles at the exciplex state. When the exciplex is formed, the induced additional dipole
will change direction and size of the dipole moment vector from those of calculated
triplet states. In case of the syn conformer, the molecular dipole will rotate clockwise

after formation of exciplex, while that of anti conformer rotate anticlockwise.

The equilibria between exciplexes from the two different modes of cycloadditions
with major conformers can be considered in explaning the observed regioselectivity. The
dipole associated with charge transfer likely prefers to align itself perpendicular and not
parallel to the molecular dipole. In case of Al-CH3, it was believed that the rate of
rotation after excitation is slower than subsequent reaction rates. The major ground state
conformation (syn), remains the same throughout the reaction and gives the syn

cyclization product.

102

'IT and CR were synthesized to demonstrate the same dipole moment effect on
regioselectivity. The fused ring systems prevent bond rotation and thus allow only one
molecular dipole moment. Irradiation of TT shows opposite regioselectivity from Al-
CH3 because it has opposite molecular dipole moment. The Scheme below illustrates

that the anti addition imparts a perpendicular interaction between the two dipoles.

 

 

   

anti addition syn addition

 

 

Figure 4 Equilibria between two addition modes of butenoxytetralone (IT) on exciplex

state.

The same result was observed in the photochemistry of CR. The structure and

direction of the molecular dipole moment of CR is a analogous to the favored anti

conformation of Al-OCH3.

103

 

 

   

anti addition

 

 

A similar explanation can be offered for the regioselectivity of acetophenones.
Fluorine substituted acetophenones can proceed through both possible cyclization modes

because fluorine is small size can allow to exist on both sides of the carbonyls.

104

3.2.2. Biradical

Two noninterconverting biradicals (BR) formed from the exciplex (EX) can
subsequently couple to form either syn or anti addition products or decay to the ground

state .

 

 

 

Figure 5. Calculated geometry of p-butenoxybenzaldehyde.

It was calculated that the C-C bond being formed has a bond distance of about
2.27 A and the angle between the double bond and the incipient bond of about 108 °.60
Since our system is analogous to the exo cyclization of a hexenyl radical,61 these results
can be applied to our system. It was believed that the transition state for the radical
addition reaction is similar in structure to the exciplex with small differences; the
distance between the ring carbon and the internal double bond carbon becomes about
2.27 A and the external double bond carbon moves away vertically from the plane of the

benzene ring to reach the 108° proposed angle of addition.

105

 

 

 

It is possible that kPS at kpa, but in order for the differential biradical partitioning to

be totally responsible for the observed regioselectivity kps and kpa must show a large
difference depending on the substituents, since there can be little difference between the

rate of the syn and anti biradical decay to the ground state of the starting material

(kds=kda)-

106

Table 11. Energy (in Kcal/mol) of biradicals (BR) of ortho substituted p-

 

 

 

 

 

butenoxybenzaldehyde
X o o
H s" H s5
X

X=CH3 -384168.5252 -384l68. 1224
X=OCH3 431 129.1497 431 128.9966
X: 421699.31099 421699.0888
X=CF3 -570274.0517 -570273.9174

 

 

 

 

 

Ab initio calculation was carried out to estimate the stability of both biradicals.
The result shows that two biradicals are similar in energy with a difference less than 1

Kcal/mol. The position of ring substituent X did not affect the stability of biradicals.

In order to form the cyclobutane ring of CH, the triplet biradical must undergo
intersystem crossing to generate a singlet biradical. Both singlet and triplet surfaces of
biradicals rise in energy along the reaction coordinate. The singlet surface is soon
stabilized during bond formation while the triplet surface continuously rises. This causes
surface crossing at a point and the ISC at this point benefits from large spin-orbital
coupling (SOC). Michl’s calculations62 suggest that soc will be strong in those
geometries in which there is a significant covalent interaction between the two radical
centers. Geometric difference by a slight puckering of the benzene ring at the ortho

carbon to the tether might change the ISC rate.

107

3.2.3. CH-CO Equilibrium

It is known from this study and other studies that substituents change the

cyclohexadiene (CH) - cyclooctatriene (CO) equilibrium.

 

  
  
      

 

Z=CHO X=CH3 < 5°/o > 95%
Z=CHO X=F < 5% > 95%
Z=CHO X=CF3 < 5% > 95%
Z=CN X=F < 5% > 95%
Z=CN X=CF3 < 93:? > 93:?
Z,X=- CH ) -CO- > o < o
Z,X=- (CI-12)2-CO- > 95% < 5°/o

  

When syn cycloaddition occurs, aldehydes with CH3, F and CF3 and nitriles with
F and CF3 substituents were found to shift the equilibrium towards the cyclooctatriene

(CO). For all those cases, no cyclohexadiene was detected by NMR during irradiation of

 

the starting aldehydes.
x
o
x
Z=CHO X=OCH3 > 95% < 5%
Z=CHO X=F < 5% > 95%
Z=CN X=CH < 5% > 95%
= = < o > 957
Z,X=-(CH2)3-CO- < 5% > 957:
Z,X=-O(CH2)2-CO- < 5% > 95%

 

 

108

For anti cycloaddition, equilibria lie toward CO. The table below shows the

result of ab initio calculations.

Table 12. Calculated energy of CH and C0 of ortho substituted p-butenoxybenzaldehyde.

 

 

 

 

 

 

 

(in Kcal/mol) CH CO

Anti addition Syn addition Anti addition Syn addition
Al-CH3 -384180.16 -384180.64 -384180.62 -384185.28
Al-OCH3 431 148.05 431 143.83 431 149.86 431149.49
Al-F 421715.39 421713.74 421720.24 421717.97
Al—CF3 -570289.42 -570283. 16 -570289.93 -570292.65

 

 

 

 

 

Results show that all substituents on the nitrile system have two regioisomers and

the equilibriums shifted to CO when the cycloaddition is either in the syn and anti modes.

Those results indicate that it is unlikely that this thermal process is responsible for the

observed regioselectivity.

109

 

3.3. Photochemistry of Benzonitrile Derivatives

Photolysis of benzonitrile derivatives produced both regioisomers in most of the
cases as compared to the results of the butenoxybenzaldehyde system, in which only

fluorine substituted benzaldehyde showed regioselectivity in both directions.

 

1:? molecular dipole

   

—> charge transfer

[: dipole
side a g side t
Syn addition

 

 

Figure 6. Dipole interaction of ortho substituted p—butenoxybenzonitrile (CN-X) for syn
addition.

For the nitrile system, the direction of molecular dipole moments on the exciplex
will align close to the middle axis going through cyano group and tether. Therefore, the
interaction between the two dipoles will be smaller than that of the benzaldehyde system.
The result suggests that the differentiating effect of the dipole moment is weak in nitrile
derivatives. Generally, triplet sensitized reaction conditions give more syn addition

products relative to direct irradiation.

110

It was found that different cyclobutene photoproducts were formed when
irradiation conditions were changed in the case of fluorine substituted benzonitrile

derivative (CN-F).

 

 

 

 

 

\\
254 nm 313 nm O
I x - NC 0 0 NC + CE"
N C O acetonitnle acetone ! O

F F

CBa

 

 

In the case of CN-CF3, the ratio of LCBa was increased from 50% to over 90%
when the reaction condition was changed from acetone sensitization to direct irradiation.

A similar tendency was observed for unsubstituted p-butenoxybenzonitrile.

254 nm 313 nm O
I \ <-—— ——-—->
NC 0 acetonitrile NC 0 acetone NC ! O

 

 

 

 

 

LCB co CB

 

 

Those observations raise many questions. It is possible that the singlet and triplet
electronic states of the nitrile system is different and undergoes a different reaction
pathway to generate different photoproducts. Gilbert performed a quenching study to

show the presence of a reaction pathway from the singlet state.45

111

Part 4. Experimental

4.1. Instrumentation

This section describes the instrumentation used to characterize all substrates

presented in this research.

‘HandnC:

FT-IR :

UV:

HPLC :

GC:

FS:

MP:

Varian Gemini 300, Varian VXR-300, and Varian VXR-500
Nicolet 42/Infrared Spectrophotometer with a 0.025 mm
212308-0 Aldrich IR cell
Joel JMS-HXI 10 Mass Spectrometer and VG Trio-1

Benchtop GC-MS with a Hewlett Packard 5890 Gas

Chromatography

Shimadzu UV—160 Recording UV-VIS

Rainin Dynamax HPLC interfaced with a dual wavelengh

programmable detector and fraction collector
Varian 1400 and 3400 Gas Chromatography with Hewlett
Packard HP3393A, HP3392A, and HP3395 Integrators

Perkin-Elmer MPF44A Fluorescence Spectrophotometer
Thomas Hoover Capillary Melting Point Apparatus

Melting Points are not corrected.

112

4.2. Chemicals

This section describes the preparation, purification, and identification of all
chemicals used in this research. A11 substrates used in the preparation of the
photoprecursors were the highest purity commercially available. The purity of such

compounds was checked by gas chromatography or 1H NMR prior to use.

4.2.1. Solvents

a. Acetonitrile‘”

Reagent-grade acetonitrile (2L) was refluxed over P205 (2g) for four hours, then
distilled through a one foot column packed with glass helices. The solvent was then
refluxed over Call; for 24 hours and then fractionally distilled through a half meter

column packed with glass helices. The middle fraction (80%) which boiled at 81-82°C

was saved and stored over type 4A Linde molecular sieves.

b. Acetone62

Capillary GC/GC-MS grade acetone (2L) was treated successively with small
amounts of KMnO4 (0.5 gram portions) until a violet color persists. Anhydrous K2CO3 (8
gram) was added and the mixture was refluxed for 12 hours. The solvent was then

fractionally distilled through a one foot column packed with glass helices. The middle

113

fraction (90%) which distilled between 56-57 °c was saved and stored over type 411

Linde molecular sieves.

c. Methanol64

Reagent-grade absolute methanol was refluxed over Mg metal (2.5 g/1200ml)
overnight, then distilled through a half meter column packed with glass helices. The

middle fraction (80%) which distilled between 64-65 °C was saved.

(1. Benzene62

Reagent-grade benzene (3.5L) was stirred over conc. H2804 (0.5L) until the acid
washing remained colorless (usually three portion of cone. H2SO4). The benzene layer
was subsequently separated, washed with distilled water (3 x 150 mL), saturated
NaHCO;; (3 x 200 ml), saturated NaCl (2 x 100 ml), and then dried over MgSO4. The
filtered benzene was then refluxed for 24 hours over P205 (150 gram). After the stated
period, the benzene was distilled through a meter column packed with stainless steel

helices. The first and last 10 % were discarded. The middle fraction distilled between at

78-80 °C.

114

4.2.2. Chromatography Material

The majority of the photoreactants were purified by silica gel chromatography
and photoproducts were purified by HPLC. Preparative thin layer chromatography
(Analtech Uniplate silica gel plates of 20 x 20 cm, 1000 micron) was utilized for samples
up to 150 miligrams. Flash chromatography (Aldrich [cat#22,719-6] silica gel, Merck,

grade 60, 230-400 mesh, 60A.) was used for larger samples.

115

4.3. Preparations of Reactants

4.3.1. 4-(3-Buten-1-oxy)-2-methylbenzaldehyde

 

0
OH 0*

,0

 

 

acetyl chloride, pyridine
»
benzene, 0°C

O/\‘\ O
I \ ‘1 . 12, pyndlne \
steam bath 0

— 2. NaOH,
LAH. HO O O
ether,
0°C

 

V

0 O/\‘\
. \ PCC , \
O NaOAc, m 0

0H

 

  

 

116

potassium carbonate

aluminium chloride
Q nitrobenzene, 0°C
0

 

 

e

acetone, reflux
N Br

 

a. 3-methylphenyl acetate

Acetyl chloride (9.74 g, 0.124 mol) was added dropwise to a mixture of m-cresol
(13.4 g, 0.124 mol) and pyridine (9.78 g, 0.124 mol) in 20 mL of dry benzene at 0°C. The
mixture was stirred under nitrogen at room temperature for 24 hours. The mixture was
hydrolyzed with 5% HCl (25 mL) and organic layer was separated. The organic layer was
extracted four times with 10 mL portions of 2 N NaOH and dried over magnesium
sulfate. The extract was concentrated in vacuo to give a crude yellow oil. Purification of

the crude product by vacuum distillation gave 3-methylphenyl acetate as a colorless

liquid (18.25 g, 98%), bp (218 °C).

1H NMR (CDC13, 300 MHz, 5 ppm): 2.28 (s, 3H), 2.36 (s, 3H), 6.92 (m, 2H), 7.02

(broad d, J = 7.8 Hz, 1H), 7.24 (dd, J = 8.4 and 7.2 Hz, 1H).

lSC-NMR(CDC13, 75 MHz, 8 ppm): 20.90, 21.10, 118.35, 122.01, 126.46, 128.98,

139.42, 150.48 and 169.42.

FT-IR (CC14, cm’l): 1209.5, 1369.6, 1489.2, 1589.6, 1614.6, 1768.95, 2924 and 3036

cm'1

GC-MS (m/z): 43.0, 77.0, 107.1, 108.1(Base), 150.1(M+°).

117

b. 4-hydroxy-2-methy[acetophenone

A solution of 3-methylphenyl acetate (15.0 g, 0.1 mol) in nitrobenzene (50 mL)
was added dropwise to a solution of aluminium chloride (26.67 g, 0.2 mol) in
nitrobenzene (200 mL) at 0°C under argon. The reaction mixture was warmed to room
temperature and stirred for 96 hours. The mixture was then hydrolyzed with 5% H0 (200
mL). The nitrobenzene layer was diluted with ether (200 mL) and extracted with 50 mL
portions of 2N NaOH. The combined aqueous washings were acidified with HCl to a pH
of 3-5 and extracted with ether (6 x 100 mL). The organic extracts were dried over
magnesium sulfate, filtered, and concentrated in vacuo. Purification by vacuum
distillation gave 4-hydroxy-2-methy1acetophenone as a white solid (7.5 g, 50%), mp

(129-131°C).

1H NMR (CDC13, 300 MHz, 5 ppm): 2.53(s, 3H), 2.54(s, 3H), 6.70(s, 1H), 6.71(d, J = 9

Hz, 1H) and 7.71(d, J =9 Hz,1H).

13C-NMR (CDC13, 75 MHz, 8 ppm): 22.54, 29.03, 112.37, 118.96, 129.50, 133.04,

142.82, 158.77 and 200.17.

Fr-IR (ccn, cm"): 1240.4, 1363.9, 1647.4 and 3182.9 cm".

GC-MS (m/z): 51.1, 77.0, 107.0, 135.0 (Base) and 150.0 (M”).

118

c. 4-(3-Buten-l-oxy)-2-methylacetophenone

4—hydroxy-2-methylacetophenone (4.0 g, 0.0266 mol), 4-bromo-1-butene (4.60
g, 0.019 mol) and anhydrous potassium carbonate (11.03 g, 0.078 mol) in dry acetone (50
mL) were refluxed under argon for 40 hours. The cooled mixture was gravity filtered to
remove the salt formed during the reaction and concentrated in vacuo. The resulting
yellow oil was diluted with ether (50 mL) and extracted with 2N NaOH (4 x 25 mL). The
organic layer was dried over magnesium sulfate, gravity filtered and concentrated in
vacuo to give a crude yellow liquid. Purification of the crude product by column
chromatography on silica gel (hexanezethyl acetate, 95:5) gave 4-buten-1’-oxy-2-

methylacetophenone in 68% yield as pale yellow liquid (3.69 g).

1H NMR (CDC13, 300 MHz, 5 ppm): 2.51 (s, 3H), 2.53 (s, 3H), 2.53 (m, 2H), 4.02 (t, J =
6.6 Hz, 2H), 5.07-5.18 (m, 2H), 5.87 (ddt, J = 18, 10.5, and 6.6 Hz, 1H), 6.71 (m, 2H)

and 7.72 (d, J = 9.6 Hz, 1H).

13C-NMR (CDC13, 75 MHz, 5 ppm): 22.58, 29.01, 33.42, 67.09, 110.92, 117.23, 117.96,

129.75, 132.51, 134.01, 142.15, 161.22 and 199.39.

FT-IR(CC14, cm'l): 1246.2, 1317.6, 1450.7, 1566.4, 1603.1, 1674.4, 2928.3 and

3050 cm".

119

GC-MS (m/z): 43.2, 55.1, 77.0, 107.2, 135.2 (Base) 150.3, 189.2 and 204.2 (M+°).

d. 4-(3-Buten-1-oxy)-2-methylbenzoic acid

Iodine (2.54 g, 0.01 mol) was added to the solution of 4-(3-buten-1-oxy)-2-
methylacetophenone (2.04 g, 0.01mol) in pyridine (5 mL). The reaction mixture was
heated on the steam bath for 30 min then stirred over night at room temperature. Excess
pyridine was removed by vacuum distillation and the residue was washed with water.
Sodium hydroxide (3g) was added to the suspension in the water (50 mL). The mixture
was heated on the steam bath for 1 hour and acidified with concentrated hydrochloric
acid. The precipitate was filtered and extracted with saturated sodium carbonate solution.
The aqueous layer was acidified with concentrated hydrochloric acid and filtered.
Purification of the crude product by column chromatography on silica gel
(chloroformzacetone, 3:1) gave 4-buten-l ’-oxy-2-methylbenzoic acid as solid (mp. 130-

132 °C) in 49% yield (1.0 g).

1H NMR (CDCl3, 300 MHz, 5 ppm): 2.53 (q, J = 6.6, 2H), 2.61 (s, 3H), 4.02 (t, J = 6.6

Hz, 2H), 5.09-5.20 (m, 2H), 5.88 (ddt, J = 17.1, 10.5, and 6.6 Hz, 1H), 6.77 (m, 2H) and

8.05 (d, J = 9.6 Hz, 1H).

120

l3C-NMR (CDC13, 75 MHz, 5 ppm): 22.69, 33.45, 67.18, 111.43, 117.32, 117.69,

120.45, 134.07, 134.09, 144.26, 162.39 and 172.79.

FF-IR(CC14,cm") : 1244.2, 1603.1, 1680.2, 2000-3350 cm“.

GC-MS (m/z) : 55.3(Base), 76.7, 105.0, 134.6, 152.0, 166.1, 178.0 and 206.1 (M").

e. 4-(3-Buten-1-oxy)-2-methylbenzyl alcohol

A suspension of lithium aluminium hydride (0.42 g, 0.011 mol) in anhydrous
ether (10 mL) was cooled in an ice bath. A solution of 4-(3-buten-1-oxy)-2-
methylbenzoic acid (1.5 g, 9 mmol) in tetrahydrofurane (25 ml) was added over 30 min
period. The mixture was stirred at RT for 3 hrs and then cooled in an ice bath while water
(25 mL) was added. The mixture was stirred overnight at RT. Magnesium sulfate was
added and stirring continued for 3 hrs. The salt was removed by filteration and washed
well with hot tetrahydrofuran and ether. Solvent was removed by vacuum distillation and
the solid was recrystalized from benzene. The aqueous layer was acidified with
concentrated hydrochloric acid and filtered. Purification of the crude product by column
chromatography on silica gel (chloroformzacetone, 3:1) gave 4-buten-l ’-oxy-2-

methylbenzoic acid as pale yellow liquid in 49% yield (0.84 g).

121

1H NMR (CDC13, 300 MHz, 5 ppm): 2.32 (s, 3H), 2.53 (q, #66 Hz, 2H), 4.00 (t, J = 6.6
Hz, 2H), 4.58 (s, 2H), 5.07-5.19 (m, 2H), 5.87 (ddt, J = 17.1, 10.5, and 6.6 Hz, 1H), 6.71

(m, 2H) and 7.72 (d, J = 8.4 Hz, 1H).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 18.86, 33.57, 63.11, 67.04, 111.28, 116.82, 116.94,

129.40, 131.07, 134.39, 137.99 and 158.45.

FF-IR (CC14, cm"): 752.3, 898.9, 991.5, 1253.9, 1383.1, 1502.7, 1608.8, 2928.3 3078.8,

3383.6 and 3609.3 cm“.

GC-MS (m/z): 39.0, 55.1(Base), 77.0, 91.1, 109.0, 120.0, 38.2, 151.1, 177.2 and

192.2(M”).

f. 4-(3-Buten-1-oxy)-2-methylbenzaldehyde

Pyridinium chlorochromate (1.8 g, 8.35 mmol) and sodium acetate (0.14 g, 1.65
mmol) were suspended in dichloromethane (12.5 mL). The mixture was stirred
vigorously by using an overhead stirrer. A solution of the 4-(3-Buten-1-oxy)-2-
methylbenzyl alcohol (0.8 g, 4 mmol) in dichloromethane (2 mL) was added and was
stirred overnight. After 15 hours, it was diluted with ether (80 mL) and filtered through a
short pad of silica gel. The ether layer was dried over magnesium sulfate, gravity filtered,

and concentrated in vacuo to give a crude yellow liquid. Purification of the crude product

122

by column chromatography on silica gel (hexanezethyl acetate, 90:10) gave 4-(3-buten-1-

oxy)-2-methylbenzaldehyde as colorless liquid in 68% yield (0.52 g).

 

 

 

1H NMR (CDC13, 300 MHz, 5 ppm): 2.52 (q, I = 6.6 Hz, 2H3), 2.60 (s, 3H”), 4.05 (t, J =
6.6 Hz, 2H7), 5.08-5.19 (m, 2H10), 5.86 (ddt, J = 17.1, 10.5, and 6.6 Hz, 1H9), 6.70 (d, J =
2.4 Hz, 1H3), 6.8 (dd, J = 8.4 Hz, 2.4 Hz, 1H5), 7.71 (d, J = 8.4 Hz, 1H6) and 10.07 (5,

1H12)-

13C-NMR (CDC13, 75 MHz, 5 ppm): 19.85, 33.35, 67.26, 111.81, 117.37, 117.43,

127.78, 133.88, 134.70, 143.21, 162.92 and 191.15.

FF-IR(CC14, cm'l): 733.0, 912.4, 1122.7, 1250.1, 1325.3, 1498.8, 1588.4, 1601.1,

1687.9, 2720, 2930.2 and 3110 cm".

GC-MS (tn/z): 38.9, 55.0(Base), 77.0, 91.0, 107.1, 124.1, 135.0, 162.1, 178.1 and

190.0(M”).

123

UV: 220.6, 269.2(max) and 297.

Anal: Calcd: C(%), 75.76; H(%), 7.42. Found: C(%), 75.16; H(%), 7.56.

4.3.2. 4-(3-Buten-l-oxy)-2-methoxylbenzaldehyde

 

 

9H3 9H3
O O
DIBAH H,
NEG-OOH: > C00“:
Hexane, -78°C 0”

Al-OCH3

 

 

4-(3-Buten-1~oxy)-2-methoxylbenzonitri1e (CN-OCH3) (0.49 g, 2.4 mmol) was
dissolved in 3 mL of dry hexane under argon atmosphere. The solution was cooled to —78
°C, and 0.04 mL of a l M hexane solution of diidobutylaluminum hydride was added.
After 1 hr, ether (10 mL) and silica (1.5 g) were added, and the mixture was kept stirring
at 4 °C for 15 hrs. Water was added, and the mixture was extracted twice with ether. The
ether layer was dried over magnesium sulfate, gravity filtered and concentrated in vacuo
to give a crude yellow liquid. Purification of the crude product by column
chromatography on silica gel (hexanezethyl acetate, 90:10) gave 4-(3-buten-1-oxy)-2-

methoxylbenzaldehyde as colorless liquid in 85% yield (0.42 g).

124

 

 

 

1H NMR (CDC13, 300 MHz, 5 ppm): 2.59 (q, J = 6.6 Hz, 21-13), 3.85 (s, 3H”), 4.08 (t, J =
6.6 Hz, 2H7), 5.10-5.20 (m, 2Hlo), 5.87 (ddt, J=17.1, 10.5, and 6.6 Hz, 1H9), 6.41 (d, J =
2.1 Hz, 1H3), 6.52 (dd, J = 8.7 Hz, 1.5 Hz, 1H5), 7.8 (d, J = 8.7 Hz, 1H6) and 10.30(s,

1H12)-

l3C-NMR (CDC13, 75 MHz, 5 ppm): 33.42, 55.59, 67.64, 98.64, 105.89, 117.59, 119.18,

130.27, 133.88, 163.04, 166.07 and 188.37.

FF-IR (CC14, cm'l): 733.0, 912.4, 1122.7, 1250.1, 1325.3, 1498.8, 1588.4, 1601.1,

1687.9, 2720, 2930.2 and 3110 cm].

GC-MS (m/z): 39.0, 55.1, 63.1, 77.1, 92.0, 108.0, 124.0, 135.0, 151.0 (Base), 165.1,

177.1 and 206.1 (M+').

UV: 228.6, 268.0(max) and 302.

125

Anal: Calcd: C(%), 69.89; H(%), 6.84. Found: C(%), 69.81; H(%), 6.79.

4.3.3. 4-(3-Buten-1-oxy)-2-fluorobenzaldehyde

 

Br 31'

O F NBS F N Br F
> ’
CH3CN, RT 0 potassium carbonate 0 /
acetone, reflux

CN

0 F DIBAH Q F ‘ CuCN 180-185°C
‘ .
hexane, -70 °C N-methylpyrrolidone

 

 

 

 

of of

 

 

a. 4-Bromo-3-fluorophenol

NBS(17.8 g, 0.1 mol) was added to 3-fluorophenol (11.2 g, 0.1 mol) in DMSO (9
g, 0.11 mol) and CH3CN (200 mL). The mixture was stirred at room temperature for 1 hr,
the solvent evaporated and the residue treated with 100 mL of ethyl ether and water (3 x
50 mL). The ethereal layer was dried over MgSO4, filtered and evaporated, and the crude

product was obtained and purified by fractional distillation at reduced pressure (b.p. 60-

126

65 £11

90:1

"a
\.—/

111‘

111‘)

146

 

 

 

GC

65 at 3.54 mmHg) followed by flash chromatography on silica gel (hexanezethyl acetate,

90:10) gave 4-Bromo-3-fluorophenol as white solid (mp. 72-73 °C) in 24 % yield (4.5

g).

1H NMR (CDC13, 300 MHz, 5 ppm): 5.19 (s, 1H), 6.53 (ddd, J = 8.7, 2.7 and 1.2 Hz,

1H), 6.64(dd, J = 9.6 and 3 Hz, 1H) and 7.34(t, J = 8.4 Hz, 1H).

FT-IR(CC14, cm"): 734.97, 843.00, 964.53, 1097.64, 1151.05, 1305.97, 1448.72,

1468.02, 1498.34, 1599.19, 2980.40 and 3206.10 cm".

GC-MS (m/z): 57.1, 83.0(Base), 95.0, 111.0, 134.8, 160.8 and 191.8(M+°).

b. 1-Bromo4-(3-buten-l-oxy)-2-fluorobenzene

4-Bromo-3-fluorophenol (4.0 g, 0.020 mol), 4-bromo-1-butene (3.3 g, 0.024 mol)
and anhydrous potassium carbonate (7 g, 0.05 mol) in dry acetone (250 mL) were
refluxed under argon for 40 hours. The cooled mixture was gravity filtered to removed
the salt formed during the reaction and concentrated in vacuo. The resulting yellow oil
was diluted with ether (100 mL) and extracted with 2N NaOH (4 x 50 mL). The organic
layer was dried over magnesium sulfate, gravity filtered and concentrated in vacuo to

give a crude yellow liquid. Purification of the crude product by column chromatography

127

on 51

fluor

13(3

133

 

 

148

(3(

Cl

on silica gel (hexanezethyl acetate, 95:5) gave 1-bromo-4~(3-buten-l-oxy)-2-

fluorobenzene as colorless liquid in 40.6 % yield (2.1 g).

1H NMR (CDC13, 300 MHz, 6 ppm): 2.51 (q, J = 5.4, 2H), 3.95 (t, J = 6.6, 2H), 5.12 (m,
2H), 5.85 (ddt, J = 17.1, 10.5, and 6.6 Hz, 1H9), 6.57 (ddd, J = 8.7, 2.7 and 1.2 Hz, 1H),

6.68 (dd, J = 9.6 and 3 Hz, 1H) and 7.37 (t, J=8.4 Hz, 1H).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 33.44, 67.73, 103.37(d), 111.85(d), 117.36, 117.38,

133.24, 133.58(d), 158.91(d) and 159.95(d).

FT-IR (CC14, cm"): 617.30, 833.35, 1022.40, 1167.08, 1290.54, 1321.41, 1468.02,

1489.24, 1663.76, 1694.98, 2985 and 3070 cm].

GC-MS (m/z): 55.1 (Base), 81.0, 93.1, 161.0, 190.0, 216.1 and 245.1 (M").

c. 4-(3-Buten-l-oxy)-2-fluorobenzonitrile

A solution of 1-bromo4-(3-buten-1-oxy)-2-fluorobenzene (2.1 g, 8.5 mmol) and
cuprous cyanide (13.6 g) in 100 mL of N-methylpyrrolidone was heated at 180-185 °C
for 21 h. It was then poured into 400 mL of a 1:1 mixture of water and concentrated
aqueous ammonium hydroxide. After the resulting mixture had been stirred with cooling

for 3 h, the mixture was extracted with ether. The ethereal layer was extracted by

128

 

 

 

1H 1'

5.12

13C

 

117.

133

G(

saturated potassium carbonate and N aOH (2N). The ether layer was dried over MgSO4,
gravity filtered and concentrated in vacuo to give a crude yellow liquid. Purification of
the crude product by column chromatography on silica gel (hexanezethyl acetate, 90:10)

gave 4-(3-uten-l-oxy)-2-fluorobenzonitrile as colorless liquid in 17.2% yield (0.27 g).

1H NMR (CDC13, 300 MHz, 8 ppm): 2.56 (br q, J = 5.4, 2H), 4.04 (t, J = 6.6 Hz, 2H),
5.12-5.21 (m, 2H), 5.86 (ddt, J = 17.1, 10.5, and 6.6 Hz, 1H9), 6.69 (dd, J = 11.1 and 2.1

Hz, 1H), 6.75 (dd, J = 8.7 and 2.7 Hz, 1H) and 7.50 (t, J = 8.7 Hz, 1H).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 33.13, 68.09, 100.30, 102.71(d), 111.64(d), 114.42,

117.76, l33.76(d), 134.20, 158.91(d) and 159.95(d).

FT-IR(CC14, cm"): 617.50, 834.10, 1024.33, 1101.49, 1172.07, 1253.89, 1302.18,

1336.84, 1498.94, 1500.02, 1574.11, 1622.34, 2231.92, 2856.94 and 2926.39cm".

GC-MS (m/z): 54.8(Base), 83.8, 100.0, 120.0, 137.0, 150.0, 163.1, 191.2(M+°).

Anal: Calcd: C(%), 69.10; H(%), 5.27; N(%), 7.33. Found: C(%), 69.02; H(%), 5.20;

N(%), 7.32.

129

 

114.

010

018

Wa
driq

yell

 

 

 

liqt

d. 4-(3-Buten-1-oxy)-2-fluorobenzaldehyde

4-(3-Buten-1-oxy)-2-fluorobenzonitrile (0.2 g, 1.05 mmol) was dissolved in 3 mL
of dry hexane under argon atmosphere. The solution was cooled to -78 °C, and 0.04 mL
of a 1 M hexane solution of diidobutylaluminum hydride was added. After 1 hr, ether (10
mL) and silica (1.5g) were added, and the mixture was kept stirring at 4 °C for 15 hrs.
Water was added, and the mixture was extracted twice with ether. The ether layer was
dried over magnesium sulfate, gravity filtered and concentrated in vacuo to give a crude
yellow liquid. Purification of the crude product by column chromatography on silica gel
(hexanezethyl acetate, 90:10) gave 4-(3—buten-1-oxy)-2-fluorobenzaldehyde as colorless

liquid in 58.9% yield (0.12 g).

 

 

 

1H NMR (CDC13, 300 MHz, 5 ppm): 2.57 (br q, J = 5.1, 2H3), 4.07 (t, J = 6.6 Hz, 2H,),
5.12-5.19 (m, 21110), 5.87 (ddt, J = 16.8, 10.2, and 6.5 Hz, 1H9), 6.62 (dd, J = 12.3 and 2.4
Hz, 1H3), 6.76 (dd, J = 8.7 and 2.4 Hz, 1H5), 7.80 (t, J = 8.7 Hz, 1H6) and 10.18 (s,

1 Haldehyde)-

l3C-NMR (CDC13, 75 MHZ, 5 ppm): 33.12, 67.92, 101.8(d), 111.52(d), 117.61, 117.64,

130.00(d), 133.47, 165.5(d), 166.15(d), and 185.81(d).

130

 

150

CC

UV

An;

 

 

 

4.3.

FT-IR (CC14, cm"): 650.09, 733.04, 910.52, 1095.71, 1129.21, 1253.89, 1437.15,

1504.67, 1577.97, 1820.41, 1689.86, 2862, and 2933 cm'l.

GC-MS (m/z): 55.1(Base), 75.0, 83.0, 95.0, 122.9, 138.9, 153.0, 166.0 and 194.0 (M+°).

UV : 216.6, 264.6(max), 283 and 292.8.

Anal: Calcd: C(%), 68.03; H(%), 5.71. Found: C(%), 67.69; H(%), 5.79.

4.3.4. 4-(3-Buten-1-oxy)-2-trifluoromethylbenzaldehyde

 

F3C

F30
DIBAH H\
Ewe/x— - were
hexane, -78°C 0”

 

Al-CF3

 

 

4-(3-Buten-1-oxy)-2-trifluoromethylbenzonitrile (CN-CF3) (0.2 g, 0.83 mmol)
was dissolved in 3 mL of dry hexane under argon atmosphere. The solution was cooled to
—78 °C, and 0.04 mL of a 1 M hexane solution of diidobutylaluminum hydride was

added. After 1 hr, ether (10 mL) and silica (1 .5 g) were added, and the mixture was kept

131

 

 

stirr

 

ethe

in V

chrt

tnfl

 

111

stirring at 4 °C for 14 hrs. Water was added, and the mixture was extracted twice with
ether. The ether layer was dried over magnesium sulfate, gravity filtered and concentrated
in vacuo to give a crude yellow liquid. Purification of the crude product by column
chromatography on silica gel (hexanezethyl acetate, 90:10) gave 4-(3-buten-l-oxy)-2-

trifluoromethylbenzaldehyde as colorless liquid in 54 % yield (0.11 g).

 

 

 

1H NMR (CDC13, 300 MHz, 5 ppm): 2.57 (br q, J = 6.6, 2H3), 4.11 (t, J = 6.6 Hz, 2H7),
5.11-5.22 (m, 2H10), 5.87 (ddt, J = 17.0, 10.2, and 6.6 Hz, 1H9), 7.11 (dd, J = 8.8 and 2.2

Hz, 1H3), 7.22 (d, J = 2.2 Hz, 1H5), 8.09 (d, J = 8.3 Hz, 1H6) and 10.23 (br s, lHaldchydc).

13C-NMR(CDC13, 75 MHz, 5 ppm): 33.23, 67.96, 112.85(q), 116.88, 117.79, 121.57,

125.21, 126.52, 131.67, 133.48, 162.95 and 187.76.

FF-IR (CC14, cm'l): 650.09, 734.0, 911.3, 1095.71, 1127.44, 1460.15, 1579.32, 1820.41,

1697.8, 2780.2, 2930.2 and 3130 cm".

GC-MS (m/z): 55.4(Base), 63.3, 75.3, 95.2, 113.2, 125.2, 145.3, 173.3, 189.3, 216.4 and

244.2 (M").

132

UV: 217.6, 269.8(max) and 290.

Anal: Calcd: C(%), 59.02; H(%), 4.54. Found: C(%), 60.38; H(%), 5.22.

4.3.5. 4-(3-Buten-l-oxy)-2-methylbenzonitrile

 

 

o\ 1. pyridine, MSC, RT

\ .

C O °F\= 2 NHa-RT > NEG or\=
HO/ 3. MSC, 0 °C

CN-CH3

 

 

4-(3-Buten-1-oxy)-2-methy1benzoic acid (2.55 g, 12.4 mmol) and dry pyridine

(85 mL) were stirred at RT. Then methyl sulfonyl chloride (MSC, 1.92 g) was added
dropwise into the reaction flask. After 1 hour dry ammonia gas was passed for 2 min. The
mixture was cooled to 0°C and additional methyl sulfonyl chloride (16 g) was added and
stirred at RT for 24 hours. The mixture was poured into diluted acid and pH was adjusted
to 7. The mixture was extracted with ethyl acetate (2X100 mL) and concentrated in vacuo
to give a crude yellow liquid. Purification of the crude product by column
chromatography on silica gel (hexanezethyl acetate, 95:5) gave 4-(3-buten-1-oxy)-2-

methylbenzonitrile as colorless liquid (1.8 g, 77.6 %).

133

 

 

 

1H NMR (CDC13, 300 MHz, 5 ppm): 2.46 (s, 3H“), 2.52 (qt, J = 6.6 and 1.6 Hz, 2H3),
4.01 (t, J = 6.6 Hz, 2H7), 5.07-5.19 (m, 2H"), 5.85 (ddt, J = 17.0, 10.4, and 6.6 Hz, 1H9),
6.71 (d, J = 2.2 Hz, 1H3), 6.75 (dd, J = 8.2, and 2.2 Hz, 1H5) and 7.47 (d, J = 8.2 Hz,

1H6).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 20.61, 33.26, 67.30, 104.32, 112.40, 116.11,

117.40, 118.54, 133.76, 134.10, 143.96, and 161.95.

FT-IR (CC14, cm'l): 721.5, 1248.1, 1377.3, 1458.4, 1498.9, 1606.9, 2224.2, 2855.0, and

2924.5 cm".

GC-MS (m/z): 39.2, 55.2(Base), 77.1, 89.0, 104.0, 116.0, 133.0, 159.1 and 187.1M").

UV: 211, 246.8(max), 275.0 and 285.

Anal: Calcd: C(%), 76.98; H(%), 7.00; N(%), 7.48. Found: C(%), 75.69; H(%), 7.13;

N(%), 7.16.

134

 

 

0.x
telr
31h:
CV3

rEdi

 

4.3.6. 4-(3-Buten-l-oxy)-2-methoxybenzonitrile

 

Br

O-CHS NBS O_CH3 NBI’ O-CHa
> >
CHacN, RT 0 potassium carbonate 0 /
acetone, reflux
0.. 0.. OJ

CN

 

 

‘

 

I o-CH3 CuCN 180-185°C

N-methylpyrrolidone

 

 

a. 4-Bromo-3-methoxy-phenol

NBS (17.8 g, 0.1 mol) was added to 3-methoxy phenol (12.4 g, 0.1 mol) in
DMSO (9 g, 0.11 mol) and CH3CN (200 mL). The mixture was stirred at room
temperature for 1 hr, the solvent evaporated and the residue treated with 100 mL of ethyl
ether and water (3 x 50 mL). The ethereal layer was dried over MgSO4, filtered and

evaporated, and the crude product was obtained and purified by fractional distillation at

reduced pressure (b.p. 72-73 °C at 3.54 mmHg) followed by flash chromatography on

135

 

G1

 

 

 

 

We

rcr

yel

01'!

Ch

0X

silica gel (hexanezethyl acetate, 90: 10) gave 4-bromo-3-methoxyphenol as white solid

(mp. 82-83 °C) in 10.8% yield (2.2 g).

1H NMR (CDC13, 300 MHz, 5 ppm): 3.86 (s, 3H), 4.9 (s, 1H), 6.33 (dd, J = 8.4 and 2.7

Hz, 1H), 6.46 (d, J = 2.7 Hz, 1H) and 7.35 (d, J=8.4 Hz, 1H).

GC-MS (m/z): 51.1, 65.1, 93.1, 108.1, 131.0, 159.0, 187.0, 204.0 (Base, M”).

b. 1-Bromo-4-(3-Buten-l-oxy)-2-methoxybenzene

4-Bromo-3-methoxy-phenol (2.0 g, 9.9 mmol), 4-bromo—1-butene (1.62 g, 12.1
mol) and anhydrous potassium carbonate (3.44 g, 0.024 mol) in dry acetone (50 mL)
were refluxed under argon for 50 hours. The cooled mixture was gravity filtered to
remove the salt formed during the reaction and concentrated in vacuo. The resulting
yellow oil was diluted with ether (50 mL) and extracted with 2N N aOH (4 x 25 mL). The
organic layer was dried over magnesium sulfate, gravity filtered and concentrated in
vacuo to give a crude yellow liquid. Purification of the crude product by column
chromatography on silica gel (hexanezethyl acetate, 95:5) gave l-bromo-4—(3-buten-l-

oxy)-2-methoxybenzene as colorless liquid in 18.1% yield (0.46 g).

136

1H NMR (CDC13, 300 MHz, 5 ppm): 2.54 (q, J = 6.59 Hz, 2H), 3.86 (s, 3H), 3.99 (t, J =
6.59Hz, 2H), 5.16 (m, 2H), 5.90 (ddt, J = 17.0, 10.4, and 6.59 Hz, 1H), 6.38 (dd, J = 8.79

and 2.75 Hz, 1H), 6.50 (d, J = 2.75 Hz, 1H) and 7.39 (d, J = 8.79 Hz, 1H).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 33.44, 55.95, 67.33, 100.32, 102.21, 106.33,

117.08, 132.95, 134.10, 156.32, and 159.35.

GC-MS (m/z): 55.1 (Base), 63.], 79.1, 93.1, 128.8, 159.0, 203.9, 257.1 (M”).

c. 4-(3-Buten-l-oxy)-2-methoxybenzonitrile

A solution of 1-bromo-4-(3-buten-1-oxy)-2-methoxybenzene (0.4 g, 1.95 mmol)

and cuprous cyanide (3.1 g) in 23.5 mL of N-methylpyrrolidone was heated at 180—185
°C for 21 h. It was then poured into 400 mL of a 1:1 mixture of water and concentrated
aqueous ammonium hydroxide. After the resulting mixture had been stirred with cooling
for 3 h, the mixture was extracted with ether. The ethereal layer was extracted by
saturated potassium carbonate and NaOH (2N). The ether layer was dried over MgSO4,
gravity filtered and concentrated in vacuo to give a crude yellow liquid. Purification of
the crude product by column chromatography on silica gel from dichloromethane gave 4-

(3-buten-1-oxy)-2-methoxybenzonitrile as pale yellow liquid in 27.8% yield (0.11 g).

137

 

 

 

1H NMR (CDC13, 300 MHz, 6 ppm): 2.52 (q, J = 6.59 Hz, 2H), 3.85 (s, 3H), 4.02 (t, J =
6.59Hz, 2H), 5.12 (m, 2H), 5.85 (ddt, J = 17.0, 10.4, and 6.59 Hz, 1H), 6.42 (d, J = 2.2

Hz, 1H), 6.47 (dd, J = 8.79 and 2.2 Hz, 1H), and 7.41 (d, J = 8.79 Hz, 1H).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 33.26, 55.91, 67.59, 98.88, 106.1, 116.94, 117.48,

133.72, 134.78, 162.73, 163.89 and 180.03.

FT-IR (CC14, cm'l): 724.7, 1115.30, 1250.1, 1451.5, 1496.3, 1612.8, 2223.7, 2877.0, and

2930.2, 3014.2 cm".

GC-MS (m/z): 55.2 (Base), 77.2, 89.2, 120.2, 132.2, 149.2, 162.3, 175.1 and 203.3

(M").

UV: 215.6(max), 247.6, 287.0 and 293.2.

138

Anal: Calcd: C(%), 70.92; H(%), 6.45; N(%), 6.89. Found: C(%), 70.95; H(%), 6.60;

N(%), 6.75.

4.3.7. 4-(3-Buten-l-oxy)-2-fluorobenzonitrile

 

o
’ch113

OH 0 OH
acetyl chloride, pyridine aluminium chloride
4 >
O F benzene, 0°C F F
0 CH3

BI'W J

“’1 ”k Cm
\ 1.pyridine.MSC, m0 \ 1.12/pyridine,RT O \
‘ ¢
0 F 2. NH, RT F 2. NaOH,

 

 

 

 

3. MSC, 0°C steam bath F
C” 0 0H 0 CH3

 

 

a. 3-fluorophenyl acetate

Acetyl chloride (9.74 g, 0.124 mol) was added dropwise to the mixture of 3-

fluorophenol (13.7 g, 0.124 mol) and pyridine (9.78 g, 0.124 mol) in 20 mL of dry

139

benzene at 0°C. The mixture was stirred under nitrogen at room temperature for 24
hours. The mixture was hydrolyzed with 5% BC] (25 mL) and organic layer was
separated. The organic layer was extracted four times with 10 mL portions of 2 N NaOH
and dried over magnesium sulfate. The extract was concentrated in vacuo to give a crude
yellow oil. Purification of the crude product by vacuum distillation gave 3-fluorophenyl

acetate as colorless liquid (18.5 g, 97%).

1H NMR (CDC13, 300 MHz, 5 ppm): 2.25 (s, 3H), 6.85 (dd, J = 2.5 and 2.3 Hz, 1H),

6.93 (ddd, J = 8.5, 2.5 and 0.9 Hz, 1H) and 7.30 (m, 2H).

13C-NMR (CDC13, 75 MHz, 5 ppm): 20.73, 109.5(d), 112.6(d), 117.25(d), 130(d),

151.4(d), 162.66(d) and 168.80.

FT-IR (CC14, cm"): 733.04, 910.52, 1122.71, 1209.52, 1371.56, 1487.31, 1601.12, and

1768.95 cm".

GC-MS (m/z): 43.1, 57.0, 64.1, 83.0, 112.0(Base) and 154.0(M+°).

b. 4-hydroxy-2-fluoroacetophenone

A solution of 3-fluorophenyl acetate (15.4 g, 0.1 mol) in nitrobenzene (50 mL)

was added dropwise to a solution of aluminium chloride (26.67 g, 0.2 mol) in

140

nitrobenzene (200 mL) at 0°C under argon. The reaction mixture was warmed to room
temperature and stirred for 96 hours. After stirring, the mixture was hydrolyzed with 5%
HC] (200 mL). The nitrobenzene layer was diluted with ether (200 mL) and extracted
with 50 mL portions of 2N NaOH. The combined aqueous washings were acidified with
HCI to pH 3-5 and extracted with ether (6 x 100 mL). The organic extracts were dried
over magnesium sulfate, filtered, and concentrated in vacuo. Purification by vacuum

distillation (b.p. 139- 140 °C at 3.54 mmHg) gave 4-hydroxy-2-fluoroacetophenone as a

white solid (6.16 g, 40 %), mp (115-117 °C).

1H NMR (CDC13, 300 MHz, 6 ppm): 2.61 (d, J = 5.2, 3H), 6.63 (dd, J = 12.6 and 2.4 Hz,
1H) 6.71 (dd, J = 8.8 and 2.4 Hz, 1H), 6.85 (s, 1H), and 7.85 (t, J = 8.8 Hz, 1H).
l3C-NMR (CDC13, 75 MHz, 6 ppm): 31.16(d), 103.56(d), 112.13, 117.20, 132.44(d),

162.17(d), 163(d), 195.80.

FT-IR (CC14, cm’l): 854.57, 1247.17, 1278.97, 1338.77, 1367.70, 1570.26, 1651.28 and

3115.43 em".

GC-MS (m/z): 43.2, 57.1, 63.1, 77.0, 83.0, 95.0, 111.0, 139.1 (Base) and 154.1 (M+°).

c. 4-(3-Buten-l-oxy)-2-fluorolacetophenone

141

4—hydroxy-2-fluorolacetophenone (4.0 g, 0.0266 mol), 4-bromo-l-butene (4.60 g,
0.019 mol) and anhydrous potassium carbonate (11.03 g, 0.078 mol) in dry acetone (50
mL) were refluxed under argon for 40 hours. The cooled mixture was gravity filtered to
removed the salt formed during the reaction and concentrated in vacuo. The resulting
yellow oil was diluted with ether (50 mL) and extracted with 2N NaOH (4 x 25 mL). The
organic layer was dried over magnesium sulfate, gravity filtered and concentrated in
vacuo to give a crude yellow liquid. Purification of the crude product by column
chromatography on silica gel (hexane:ethyl acetate, 90: 10) gave 4-buten-1’-oxy-2-

fluoroacetophenone as colorless liquid in 55% yield (3.04 g).

1H NMR (CDC13, 300 MHz, 5 ppm): 2.51 (s, 3H), 2.53 (s, 3H), 2.53 (m, 2H), 4.02 (t, J =
6.6 Hz, 2H), 5.07-5.18 (m, 2H), 5.87 (ddt, J=18, 10.5, and 6.6 Hz, 1H), 6.71 (m, 2H) and

7.72 (d, J=9.6 Hz, 1H).

13C-NMR(CDC13, 75 MHz, 5 ppm): 22.58, 29.01, 33.42, 67.09, 110.92, 117.23, 117.96,

129.75, 132.51, 134.01, 142.15, 161.22 and 199.39.

FT-IR (CC14, cm’l): 839.14, 968.39, 1130.43, 1165.15, 1259.68, 1361.92, 1435.22,

1574.11, 1618.48, 1680.21, 2945.66 and 3077.4 cm".

GC-MS (m/z): 42.9, 54.9 (Base), 63.0, 82.9, 93.6, 109.9, 138.8, 153.8, 179.9, 192.9 and

207.9 (M”).

142

d. 4-(3-Buten-l-oxy)-2-fluorobenzoic acid

Iodine (4.3 g, 0.017 mol) was added to the solution of 4-(3-buten-l-oxy)-2-
fluoroacetophenone (3.5 g, 0.017 mol) in pyridine (10 mL). The reaction mixture was
heated on the steam bath for 30 min then stirred over night at room temperature. Excess
pyridine was removed by vacuum distillation and the residue was washed with water.
Sodium hydroxide (5 g) was added to the suspension in the water (50 ml). The mixture
was heated on the steam bath for 1 hour and acidified with concentrated hydrochloric
acid. Precipitation was filtered and extracted with saturated sodium carbonate solution.
The aqueous layer was acidified with concentrated hydrochloric acid and filtered.
Purification of the crude product by column chromatography on silica gel (chloroform:
acetone, 3: 1) gave 4-buten-l’-oxy-2-fluorobenzoic acid as yellowish solid (mp. 143-145

°C) in 49% yield (1.75 g).

1H NMR (CDC13, 300 MHz, 5 ppm): 2.55 (qt, J = 6.6 and 1.0 Hz, 2H), 4.04 (t, J = 6.6

Hz, 2H), 5.08-5.20 (m, 2H), 5.86 (ddt, J = 17, 10.4, and 6.6 Hz, 1H), 6.63 (dd, J = 12.6

and 2.2 Hz, 1H) 6.72 (dd, J = 8.8 and 2.2 Hz, 1H) and 7.95 (t, J = 8.8 Hz, 1H).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 33.23, 67.85, 102.7(d), 110.78(d), 117.63, 133.4,

133.62, 134.06, 164.1(d), 164.5(d) and 169.16.

143

I‘T-IR (CC14, cm'l): 642.38, 846.86, 933.87, 1020.47, 1178.66, 1244.24, 1300.19,

1452.58, 1620.41, 1692.14 and 2953 cm“.

GC-MS (m/z): 55.3 (Base), 83.1, 94.1, 121.0, 138.9, 155.9, 169.0, 182.0 and 210.1

(M").

e. 4-(3-Buten-l-oxy)-2-fluorobenzonitrile

4-(3-Buten-1-oxy)-2-fluorobenzoic acid (1.5 g, 7.14 mmol) and dry pyridine (85
mL) were stirred at RT. Then methyl sulfonyl chloride (MSC, 1.13 g) was added
dropwise into the reaction flask. After 1 hour, dry ammonia gas was passed for 2 min.
The mixture was cooled to 0°C and additional methyl sulfonyl chloride (9.44 g) was
added and stirred at RT for 20 hours. The mixture was poured into diluted acid and pH
was adjusted to 7. The mixture was extracted with ethyl acetate (2X100 mL) and
concentrated in vacuo to give a crude yellow liquid. Purification of the crude product by
column chromatography on silica gel (hexanezethyl acetate, 95:5) gave 4-(3-buten-l-

oxy)-2-fluorobenzonitrile as colorless liquid ( 0.97 g, 71%).

 

 

 

144

1H NMR(CDC13, 300 MHz, 6 ppm): 2.54 (qt, J = 6.6 and 1.6 Hz, 2H8), 4.03 (t, J = 6.6
Hz, 2H7), 5.09-5.20 (m, 2Hm), 5.84 (ddt, J = 17.0, 10.4, and 6.6 Hz, 1H9), 6.68 (dd, J =

11 and 2.2 Hz, 1H3), 6.73 (dd, J = 8.8 Hz and 1.6 Hz, 1H5) and 7.49 (d, J = 8.8 Hz, 1H5).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 33.06, 68.06, 92.74, 102.7(d), 111.6(d), 114.38,

117.72, 133.36, 134.1, 164.1(d) and 164.5(d).

 

FT-IR (CC14, cm'l): 634.66, 839.14, 920.16, 989.61, 1022.40, 1115.00, 1172.87,

1300.19, 1506.60, 1572.18, 1622.34, 2231.92, 2936.03 and 3060 cm".

GC-MS (m/z): 39, 55 (Base), 63, 82, 93, 100, 108, 120, 137, 150, 163 and 191 (M+°).

UV: 207.0, 243.6(max), 276.8 and 283.2.

Anal: Calcd: C(%), 69.10; H(%), 5.27; N(%), 7.33. Found: C(%), 69.02; H(%), 5.20;

N(%), 7.32.

145

 

4.3.8. 4-(3-Buten-l-oxy)-2-trifluoromethylbenzonitrile

 

Br Br

0 o N:
> >
CH3CN potassium carbonate 0 /
acetone, reflux
OH OH 0

CN

 

 

 

CFa ‘ CuCN 180-185°C
O N-methylpyrrolidone

of

 

 

a. 4-Bromo-3-trifluoromethyl-phenol

NBS (17.8 g, 0.1 mol) was added to 3-trifluoromethylphenol (16.2 g, 0.1 mol) in
DMSO (9 g, 0.11 mol) and CH3CN (200 mL). The mixture was stirred at room
temperature for 1 hr, the solvent evaporated and the residue treated with 100 mL of ethyl
ether and water (3 x 50 mL). The ethereal layer was dried over MgSO4, filtered and
evaporated, and the crude product was obtained and purified by fractional distillation at
reduced pressure (b.p. 75-76 °C at 3.54 mmHg) followed by flash chromatography on
silica gel (hexanezethyl acetate, 90: 10) gave 4-bromo-3-methoxyphenol as white solid

(mp. 77 — 79 °C) in 21.6% yield (5.2 g).

146

 

1H NMR (CDC13, 300 MHz, 5 ppm): 5.60 (s, 1H), 6.84 (dd, J = 8.8 and 2.7 Hz, 1H),

7.15 (d, J = 2.7 Hz, 1H) and 7.50 (d, J = 8.8, 1H).

13C-NMR (CDC13, 75 MHz, 6 ppm): 110.05, 115.24(q). 119.94, 122.37(q), 131.02,

135.96 and 154.60.

GC-MS (m/z): 40.1 (Base), 71.1, 83.1,113.1,132.1,161.1,l92.0, 221.0, 241.0 (M”).

b. l-Bromo-4-(3-buten-l-oxy)-2-trifluoromethylbenzene

4-Bromo-3-trifluoromethylphenol (3.0 g, 12.5 mmol), 4-bromo-l-butene (2.03 g,
15 mmol) and anhydrous potassium carbonate (6.0 g, 43.4 mmol) in dry acetone (250
mL) were refluxed under argon for 51 hours. The cooled mixture was gravity filtered to
removed the salt formed during the reaction and concentrated in vacuo. The resulting
yellow oil was diluted with ether (200 mL) and extracted with 2N NaOH (4 x 100 mL).
The organic layer was dried over magnesium sulfate, gravity filtered and concentrated in
vacuo to give a crude yellow liquid. Purification of the crude product by column
chromatography on silica gel (hexanezethyl acetate, 90: 10) gave l-bromo-4-(3-buten-1-

oxy)-2-trifluoromethylbenzene as pale yellow liquid in 42.5% yield (1.57 g).

147

1H NMR (cpch, 300 MHz, 6 ppm): 2.54 (br q, J = 6.6 Hz, 2H), 3.99 (t, J = 6.6 Hz, 2H),
5.10520 (m, 2H), 5.87 (ddt, J = 17.03, 10.44, and 6.60 Hz, 1H), 6.88 (dd, J = 8.8 and

2.75 Hz, 1H), 7.20 (d, J = 2.75 Hz, 1H) and 7.54 (d, J = 8.8, 1H).

l3C-NMR (CDC13, 75 MHz, 6 ppm): 34.18, 68.53,]10.20, 115.03(q). 117.91, 119.16,

122.86(q), 130.21, 134.27, 136.15 and 158.1.

GC-MS (m/z): 55.2 (Base), 149.1, 175.1, 217.2, 253.0, 295.1 (M").

c. 4-(3-Buten-1-oxy)-2-trifluoromethylbenzonitrile

A solution of 1-bromo4-(3-buten-l-oxy)-2-trifluoromethylbenzene (1.3 g, 4.4
mmol) and cuprous cyanide (7.9 g, mol) in 100 mL of N-methylpyrrolidone was heated at
180-185 °C for 21 h. It was then poured into 500 mL of a 1:1 mixture of water and
concentrated aqueous ammonium hydroxide. After the resulting mixture had been stirred
with cooling for 3 h, the mixture was extracted with ether. The ethereal layer was
extracted by saturated potassium carbonate and NaOH (2N). The ether layer was dried
over MgSO4, gravity filtered and concentrated in vacuo to give a crude yellow liquid.
Purification of the crude product by column chromatography on silica gel (hexane:ethyl
acetate, 90: 10) gave 4-(3-buten-1-oxy)-2-trifluoromethylbenzonitrile as colorless liquid

in 65.2% yield (0.69 g).

148

 

 

 

1H NMR (CDC13, 300 MHz, 5 ppm): 2.57 (br q, J = 6.6 Hz, 2H), 4.10 (t, J = 6.6 Hz, 2H),

 

5.11-5.21 (m, 2H), 5.85 (ddt, J = 17.03, 9.9, and 6.60 Hz, 1H), 7.08 (dd, J = 8.2 and 2.2

Hz, 1H), 7.24 (d, J = 2.2 Hz, 1H) and 7.73 (d, J = 8.2, 1H).

13C-NMR(CDC13, 75 MHz, 6 ppm): 33.24, 68.87, 102, 115.03(q), 116.30, 117.58,

118.37, 122.5(q). 130.21, 133.69, 137.04, 162.4.

FT-IR (CC14, cm'l): 841.2, 920.16, 989.61, 1022.40, 1115.00, 1172.87, 1300.19,
1506.60, 1572.18, 1622.34, 2227.3, 2947.3 and 3021.0 cm".

GC-MS (m/z): 55.2(Base), 69.1, 108.2, 120.1, 139.2, 151.0, 170.2, 187.2, 200.2, 213.2
and 241.2 (M”).

UV: 208.8, 248.6(max), 277 and 290.

Anal: Calcd: C(%), 59.75; H(%), 4.18; N(%), 5.81. Found: C(%), 60.76; H(%), 4.53;

N(%), 5.46.

149

4.3.9. 6-(3-Buten-1 -oxy)-l-tetralone

 

O

o
F
O/CHs DMSO, 180 °c OH

 

 

 

N Br
\ 4
J/\ potassium carbonate
0 acetone, reflux

 

 

a. 6-Hydroxy-1-tetralone

Methoxytetralone (5.29g, 30 mmol) and sodium cyanide (7.5g, 150 mmol) are
added to DMSO (40 mL). The reaction mixture was heated at 180 °C for 5 h under
nitrogen. The mixture was poured into ice-water and acidified with 6N HCl. The
resulting precipitation is collected by filteration, washed with water, and dried.
Recrystalization from benzene gives 6-hydroxy-l-tetralone as pale yellow crystals (2.5 g,

51%), mp. 154-157 °C.

150

1H NMR (CDC13, 300 MHz, 6 ppm): 2.08 (q, J = 6.3 Hz, 2H), 2.61 (t, J = 6.3 Hz, 2H),
2.87 (t, J =6 .3 Hz, 2H), 6.70 (d, J = 1.8 Hz, 1H), 6.79 (dd, J = 8.7 and 1.8 Hz, 1H) 7.6 (br

s, 1H) and 7.96 (d, J = 8.7 Hz, 1H).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 23.24, 29.89, 38.77, 114.62, 114.64, 125.66,

130.18, 147.83, 161.34 and 198.76.

FF-IR (CC14, cm’l): 455.20, 538.26, 652.02, 835.28, 895, 1110.98, 1288.61, 1348.41,

1560.61, 1652.5, 2708.4, 2948.5, 3078.2, 2500-3500 cm".

GC-MS (m/z): 51.0, 66.0, 77.0, 91.1, 106.1, 134.0(Base), 147.1 and 162.1(M+°).

b. 6-(3-Buten-l-oxy)-l-tetralone

6-Hydroxy-1-tetralone (1.62 g, 0.01 mol), 4-bromo-1-butene (2.7 g, 0.02 mol) and
anhydrous potassium carbonate (5.5 g, 0.04 mol) in dry acetone (150 mL) were refluxed
under argon for 42 hours. The cooled mixture was gravity filtered to removed the salt
formed during the reaction and concentrated in vacuo. The resulting yellow oil was
diluted with ether (50 mL) and extracted with 2N NaOH (4 x 30 mL). The organic layer
was dried over magnesium sulfate, gravity filtered and concentrated in vacuo to give a

crude yellow liquid. Purification of the crude product by column chromatography on

151

silica gel (hexane : ethyl acetate, 90: 10) gave 6-(3-buten-1-oxy)-l-tetralone as pale

yellow liquid in 46.8% yield (1.01 g).

 

 

 

1H NMR (CDC13, 300 MHz, 6 ppm): 2.09 (q, J = 6.6 Hz, 2H3), 2.53 (q, J = 6.6 Hz,
2Hm), 2.58 (t, J = 6.6 Hz, 2114), 2.90 (t, J = 6.6 Hz, 2112), 4.05 (t, J = 6.6 Hz, 2H9), 5.10—
5.21 (m, 21112), 5.86 (ddt, J = 17.03, 9.9, and 6.60 Hz, 1H“), 6.69 (d, J = 2.4 Hz, 1H5),

6.80 (dd, J = 9 and 2.4 Hz, 1H7) and 7.98 (d, J = 9 Hz, 1H3).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 23.29, 30.04, 33.36, 38.80, 67.19, 113.07, 113.33,

117.26, 126.15, 129.49, 133.94, 146.87, 162.79 and 197.11.

FT -IR (CC14, cm'l): 650.09, 731.11, 906.66, 1035.91, 1126.57, 1258.03, 1350.34,

1495.02, 1599.19, 1670.57 and 2947.61em".

GC-MS (m/z): 55.0, 76.9, 89.0, 106.1, 134.0(Base), 147.0, 162.0, 204.1 and 216.1(M+').

Anal: Calcd: C(%), 77.75; H(%), 7.46. Found: C(%), 76.88; H(%), 7.54.

152

4.3.10. 6-(3-Buten-l-oxy)-l-chromonone

 

 

acrylonitrile/NaOCHa NC
>
reflux \L

acetic acid,
sulfuric acid, reflux
H20

 

 

V

O O
F - Ni
0 O potassium carbonate 0 OH

acetone, reflux

 

CR

 

 

a. 3-(3-Hydroxyphenoxy) propanenitrile

A mixture of resorcinol (11g, 0.1 mol), acrylonitrile (10 mL) and sodium
methoxide (1.08 g, 0.02 mol) was refluxed for 7 h. Excess of acrylonitrile was distilled
off and the residue was extracted with CHC13. The organic layer was washed, dried with
CaClz and concentrated. The residue was repeatedly extracted with ether and the layer
was dried over magnesium sulfate, gravity filtered and concentrated in vacuo to give a

crude yellow liquid. Purification of the crude product by column chromatography on

153

silica gel (hexanezethyl acetate, 90: 10) gave 3-(3-hydroxyphenoxy) propanenitrile as

white solid ( m.p. 85-86, lit. 87-88”) in 23.6% yield (3.85 g).

1H NMR (CDC13, 300 MHz, 6 ppm): 2.79(t, J=6.3 Hz, 2H), 4.13(t, J=6.6 Hz, 2H),

5.57(s, 1H), 6.39(d, J=2.3 Hz, 1H), 6.46(m, 2H) and 7.12(t, J=8.2 Hz, 1H).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 18.52, 62.48, 102.41, 106.66, 109.01, 120.35,

130.32, 156.97 and 158.88.

FF-IR (CC14, cm'l): 979.4, 1054.5, 1154.6, 1179.7, 1242.2, 1292.4, 1342.5, 1486.4,

1611.6, 2268.87, 2944.9, 3032.6 and 3351.8 cm'l.

GC-MS (m/z): 39.0, 53.0, 65.0, 82.1, 93.0, 110.0 (Base), 123.1 and 163.1 M").

b. 2,3-Dihydro-7-hydroxy-4H-benzopyran4-one

3-(3-Hydroxyphenoxy) propanenitrile (3.0 g, 18.4 mmol) in concentrated
sulphuric acid-glacial acetic acid-water (1: 1 :1 15 mL) was refluxed for 5h. The deep red
mixture was taken up in ether, washed with saturated. Sodium bicarbonate and water,
dried over sodium sulfate and evaporated. Purification of the crude product by column
chromatography on silica gel (CHCl3zMeOH, 9: 1) gave 2,3-dihydro-7-hydroxy4H-

benzopyran4-one as white solid ( mp. 146-148, lit. 147-148”) in 10% yield (0.3 g).

154

1H NMR (CDC13, 300 MHz, 6 ppm): 2.77 (t, J = 6.4 Hz, 2H), 4.50 (t, J = 6.4 Hz, 2H),
6.40 (d, J = 2.3 Hz, 1H), 6.55 (dd, J = 8.6 and 2.3 Hz, 1H) 7.0 (s, 1H) and 7.81 (d, J = 8.6

Hz, 1H).

c. 2,3-Dihydro-7-(3-buten-l-oxy)4H-benzopyran4-one

2,3-Dihydro-7-hydroxy4H-benzopyran4-one (0.25 g, 1.5 mmol), 4-bromo-1-
butene (0.41 g, 3 mmol) and anhydrous potassium carbonate (0.82 g, 5.9 mmol) in dry
acetone (25 mL) were refluxed under argon for 40 hours. The cooled mixture was gravity
filtered to removed the salt formed during the reaction and concentrated in vacuo. The
resulting yellow oil was diluted with ether (25 mL) and extracted with 2N NaOH (4 x 10
mL). The organic layer was dried over magnesium sulfate, gravity filtered and
concentrated in vacuo to give a crude yellow liquid. Purification of the crude product by
column chromatography on silica gel (hexanezethyl acetate, 90: 10) gave 2,3-dihydro-7-

(3-buten-l-oxy)4H-benzopyran4-one in 48.8% yield (0.16 g).

 

8 11
71 \
than
30 o9

 

 

155

 

 

1H NMR (CDC13, 300 MHz, 6 ppm): 2.50 (q, J = 6.6 Hz, 2H), 2.70 (t, J = 6.9 Hz, 2H),
3.99 (t, J = 6.6 Hz, 2H), 4.46 (t, J = 6.9 Hz, 2H), 5.06-5.16 (m, 21112), 5.83 (ddt, J =
17.03, 9.9, and 6.60 Hz, 1H“), 6.35 (d, J = 2.1 Hz, 1H), 6.52 (dd, J = 8.7 and 2.1 Hz, 1H)

and 7.77 (t, J = 8.7 Hz, 1H).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 33.22, 37.31, 67.256, 67.42, 101.18, 110.12,

115.12, 117.34, 128.74, 133.76, 163.66, 165.162 and 190.39.

FT-IR (CC14, cm'l): 778.2, 981.6, 1049.7, 1166.8, 1187.4, 1190.6, 1238.8, 1294.1,

1344.6, 1487.9, 1566.2, 1613.0, 2976.1, and 3027.5 cm".

GC-MS (m/z): 55.1(Base), 63.0, 80.0, 91.0, 108.0, 119.0, 136.0, 147.0, 164.0, 177.0,

190.1 and 218.1 (M”).

Anal: Calcd: C(%), 71.54; H(%), 6.47. Found: C(%), 70.96; H(%), 6.40.

156

4.4 General Procedures

Small Scale irradiations were carried out using about 0.2 mg of reactant in 0.75
mL of deuterated acetonitrile or acetone in an NMR tube. The NMR tubes were sealed by
a rubber stopper with Teflon tape over it. A long needle was inserted through the stopper
for inflowing gas and a short needle for a vent. The sample solutions were degassed by
bubbling with argon gas for 20 min. The irradiation sources included a medium pressure
mercury arc lamp and a Rayonet reactor. The light from the source was filtered through a
Pyrex or 313 nm filter solution. Samples for irradiation with 254 nm were placed in 5 mL

quartz tubes.

Large scale irradiation were done using 0.1-0.2 g of reactants in degassed solvent
such as acetonitrile and acetone in a 13 x 100 mm Pyrex culture tubes. The samples were
degassed by argon-bubbling for 30 min. The photoreactions were monitored by HPLC
and NMR. The ratios of isomers were measured by NMR analysis. The photoproducts
were isolated by preparative TLC or HPLC. HPLC was operated with a Rainin column

(Si-80-125-C5) at the flow rate of 0.8 mllmin.

Thermal chemistry of photoproducts (CB) was examined using 0.1-0.2 mg of

photoproducts in 0.75 mL of deuterated methanol.

Cyclooctatn'enes (CO) were irradiated to confirm the formation of corresponding

photoproducts (CB).

157

 

4.5. Identification of Photoproducts

4.5.1. Photolysis of 4-(3-buten-l-oxy)-2-methylbenzaldehyde

In an NMR tube, 4-(3-buten-1-oxy)-2-methylbenzaldehyde (1.9 mg, 0.01 mmol)
was dissolved in deuterated acetonitrile (0.75 mL, 1.3 x 10'2 M). The sample was purged
with argon for 15 minutes and then irradiated with a medium pressure mercury arc lamp
through a Pyrex filter sleeve. Reaction progress was monitored by 1H NMR and HPLC.
After three hours of irradiation, NMR analysis of the reaction mixture showed the

presence of several photoproducts.

Large scale photolysis was carried out to isolate the photoproducts. 4-(3-Buten-1-
oxy)-2-methylbenzaldehyde (150 mg, 0.79 mmol) was dissolved in freshly distilled
acetonitrile (50 mL) and irradiated in an immersion well with a medium pressure mercury
arc lamp through a Pyrex filter. The reaction progress was monitored by HPLC. The
reaction mixture was concentrated at reduced pressure and separated using preparative
TLC (hexane:ethy1 acetate, 80:20) followed by HPLC isolation (hexane:ethyl acetate,
80:20). Al-CH3-C0t (11 mg, 7.3% yield) was collected at 3.5 minutes but Al-CH3-CBt

could not be isolated due to its thermal instability.

158

 

 

 

6 7 9
H m hv, pyrex 8
kg 0 — .. - 1. +
O acetonltnle,RT H O

032

 

“'0'“ Al-CHa-CO AI-CH3-CB

hv T

 

 

a. 4-Formyl-5-rnethyl-ll-oxabicyclo[6.3.0]undeca-1,3,5-triene (Al-CH3-C0t)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.87 (s, 3H), 1.88-2.08 (m, 2H9), 2.153 (ddd, J =
13.2, 7.5 and 6 Hz, 1H7), 2.51 (ddd, J = 13.2, 8.2 and 4.4 Hz, 1H7), 3.05 (m, 1H3), 4.04
(ddd, J = 11, 8.8 and 6 Hz, lHlo), 4.24 (m, lHlo), 5.40 (dd, J = 6.6 and 2.2 Hz, 1H2), 5.93

(qdd, J = 8.2, 7.5 and 1.6 Hz, 1H5), 6.77 (dd, J = 6.6 and 1.1 Hz, 1H3), 9.39 (s, lHajdchyde).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 22.2, 27.8, 32.0, 44.1, 69.7, 95.8, 130.1, 134.7,

139.9, 149.0, 169.5 and 194.4.

GC-MS (m/z): 55.0(Base), 64.9, 77.0, 91.0, 104.9, 121.0, 134.9, 148.9, 162.1, 175.0 and

190.1(M+°).

159

b. l-Formyl-8-oxatricyclo[7.2.0.095]undeca-2,10-diene (Al-CH3-CBt)
1H NMR (CDC13, 300 MHz, 5 ppm): selected signals: 5.62 (m, 1H3), 6.37 (d, J = 3H2,

1H”), 6.42 (d, J = 3H2, lHto), 9.40 (s, lHaldchydc).

4.5.2. Photolysis of 4-(3-buten-1-oxy)-2-methoxybenzaldehyde

In an NMR tube, 4-(3-buten-l-oxy)-2-methoxybenzaldehyde (2.2 mg, 0.011
mmol) was dissolved in deuterated acetonitrile (0.75 mL, 1.41 x 10’2 M). The sample was
purged with argon for 15 minutes and then irradiated with a medium pressure mercury
arc lamp through a Pyrex filter sleeve. Reaction progress was monitored by 1H NMR and
HPLC. After four hours of irradiation, NMR analysis of the reaction mixture showed the

presence of several photoproducts.

Large scale photolysis was carried out to isolate the photoproducts. 4-(3-buten-
1-oxy)-2-methoxybenzaldehyde (135 mg, 0.66 mmol) was dissolved in freshly distilled
acetonitrile (50 mL) and irradiated in an immersion well with a medium pressure mercury
arc lamp through a Pyrex filter. The reaction progress was monitored by HPLC. The
reaction mixture was concentrated at reduced pressure and separated using preparative
TLC (hexanezethyl acetate, 80:20). One major product was identified by NMR analysis as
3-formyl4-methoxy- 1 l-oxatricyclo[6.3.0.0l ’6]undeca-2,4-diene (Al-CHBO-CHa) (15

mg, l 1.1% yield).

160

 

 

9H3
0 2
O acetonltnle,RT O 8
7

Al-OCHS Al-OCHS-CHa

 

   

3-Formyl4-methoxy-ll-oxatricyclo[6.3.0.0l"]undeca-2,4-diene (Al-CH30-CHa)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.96 (tdd, J = 16.11, 7.81 and 7.32 Hz, 2H9), 2.17
(dddd, J = 17.09, 5.37, 2.44, and 1.95 Hz, 1H7), 2.42 (m, 1H3), 2.70 (dd, J = 17.09 and
2.44 Hz, 1H,), 3.37 (br (1, J = 4.9, 1H6), 3.64 (s, 3HMc), 3.82 (m, 2Hm), 4.66 (s, 1H2),

6.78 (dd, J = 5.37 and 2.93 Hz, 1H5) and 9.47 (s, lHaldchydc).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 21.27, 28.96, 36.92, 52.02, 56.96, 65.48, 82.40,

96.81, 139.65, 147.63, 156.41, 193.49.

161

4.5.3. Photolysis of 4-(3-buten-l-oxy)-2-fluorobenzaldehyde

 

 

    

F 6 7 8 9
H 5
o w - .
O acetonltnle,FiT O
0 11 10 F 2
Al-F
Al-F-CBt Al-F-COa

 

 

In a NMR tube, 4-(3-buten-1-oxy)-2-fluorobenzaldehyde (2.1 mg, 0.011 mmol)

was dissolved in deuterated acetonitrile (0.75 mL, 1.44 x 10’2 M). The sample was purged
with argon for 15 minutes and then irradiated with a medium pressure mercury arc lamp
through a Pyrex filter sleeve. Reaction progress was monitored by 1H NMR and HPLC.
NMR analysis of the reaction mixture showed the presence of two major photoproducts

among several products in 2:1 ratio and one of them was thermally unstable.

Large scale photolysis was carried out to isolate the photoproducts. 4-(3-buten-l-
oxy)-2-fluorobenzaldehyde (160 mg, 0.82 mmol) was dissolved in freshly distilled

acetonitrile (50 mL) and irradiated in an immersion well with a medium pressure mercury

162

arc lamp through a Pyrex filter. The reaction progress was monitored by HPLC. The
reaction mixture was concentrated at reduced pressure and separated using preparative
TLC (hexanezethyl acetate, 80:20) followed by HPLC (hexanezethyl acetate, 80:20). Two
major products were identified by NMR analysis as 4-formy1-3-fluoro-l l-
oxabicyclo[6.3.0]undeca-1,3,5-triene (Al-F-COa) (4 mg, 2.5% yield) and 4-formyl-2-
fluoro-l l-oxabicyclo[6.3.0]undeca-l,3,5-triene (Al-F-COt) (10.7 mg, 6.7% yield) in
1:2.68. Al-F-COt was collected at 6.5 minutes and Al-F-COa was collected at 9.5
minutes from HPLC. One of the products in NMR scale reaction turned out to be Al-F-

COt.

a. 4-Formyl-3-fluoro-1l-oxabicyclo[6.3.0]undeca-l,3,5-triene (Al-F-COa)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.87 (dddd, J = 12.08, 10.99, 7.69 and 6.59 Hz,
1H9), 2.25 (dddd, J = 12.08, 11.54, 8.24 and 7.69 Hz, 1H9), 2.43 (dd, J = 11.74 and 5.49
Hz, 2H7), 3.32 (m, 1H3), 4.35 (ddd, J = 8.79, 8.24 and 7.69 Hz, 2H10), 5.40 (d, J = 10.44
Hz, 1H2), 5.89 (dt, J = 12.64 and 5.49 Hz, 1Ho) and 6.15 (dd, J=12.64 and 4.4 Hz, 1H5)

and 10.09 (S, lHaldehyde)o

l3C-NMR (CDC13, 75 MHz, 5 ppm): 19.40, 33.65, 67.09, 73.27, 112.05, 116.5(d),

127.89, 134.45, 137.70, 160.50(d), 206.60.

163

GC-MS (m/z): 55.1(Base), 77.0, 83.0, 97.0, 109.0, 115.0, 138.0 165.1, 179.0 and 194.1

(M"‘).

b. 4-Formyl-2-fluoro-l1-oxabicyclo[6.3.0]undeca-1,3,5-triene (Al-F-COt)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.86 (d quartet, J = 13.19 and 6.59 Hz, 1H9), 2.20
(d quartet, J = 14.28 and 7.14 Hz, 1119-), 2.31 (dtd, J = 15.93, 9.34 and 7.14 Hz, 1H7),
2.53 (d quartet, J = 15.9 and 3.3 Hz, 1H7), 3.05 (m, 1H3), 4.23 (dt, J = 8.79 and 7.14 Hz,
11110), 4.33 (dt, J = 8.79 and 6.59 Hz, 11110:), 5.57 (d, J = 6.59 Hz, 1H2), 5.76 (dt, J =

23.07 and 6.59 HZ, 1H6) and 7.08 (d, J = 7.14 Hz, ”'13) and 9.46 (S, lHaldehyde)-

l3C-NMR (CDC13, 75 MHz, 5 ppm): 27.99(d), 31.23, 41.38, 70.02, 96.37, 111.36(d),

128.35(d), 148.63(d), 154.99, 173.19 and 191.23.

GC-MS (m/z): 55.1(Base), 77.0, 83.0, 97.0, 109.0, 115.0, 138.0, 151.0, 166.0 and 194.1

(M+°).

164

4.5.3.1. Irradiation of 4-formyl-2-fluoro-lloxabicyclo[6.3.0]undeca-l,3,5-triene

(Al-F-COt).

 

 

 

 

N'F'CO' Al-F-CBt

 

 

In an NMR tube, 4-formy1-2-fluoro-1l-oxabicyclo[6.3.0]undeca-1,3,5-triene (Al-
F-COt) (2.0 mg, 0.01 mmol) was dissolved in deuterated acetonitrile (0.75 mL). The
sample was purged with argon for 15 minutes and then irradiated with a medium pressure
mercury arc lamp through a Pyrex filter sleeve. Reaction progress was monitored by 1H
NMR and HPLC. NMR analysis of the reaction mixture showed the presence l-formyl-2-

fluoro-8-oxatricyclo[7.2.0.09'5]undeca-2,10-diene (Al-F-CBt).

1-Formyl-2-t'luoro-8-oxatricyclol7.2.0.0"5]undeca-2,10-diene (AI-F-CBt)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.89 (H6), 2.01 (H4), 2.15 (H6), 2.25 (H5), 2.38

(H4), 3.81 (t, J = 5.49, 2H7), 5.44 (ddd, J = 15.93, 6.04 and 3.85 Hz, 1H3), 6.39 (d, J =

2.75 Hz, 1H”), 6.45 (t, J = 2.75 Hz, lHlo).

165

4.5.4. Photolysis of 4-(3-Buten-1-oxy)-2-trifluoromethylbenzaldehyde

 

"' O of—\___ hv, pyrex

acetonitrile,F1T

 

Al-CF3 Al-CF3-CBt

 

 

In an NMR tube, 4-(3-buten-1-oxy)-2-trifluoromethylbenzaldehyde (2.0 mg,

0.0082 mmol) was dissolved in deuterated acetonitrile (0.75 mL, 1.1 x 10’2 M). The
sample was purged with argon for 15 minutes and then irradiated with a medium pressure
mercury arc lamp through a Pyrex filter sleeve. Reaction progress was monitored by 1H
NMR and HPLC. NMR analysis of the reaction mixture showed the presence of one
major photoproduct among several products after 2 hours of irradiation. After overnight
at room temperature, the initial product converted to another product, which absorbs UV

light at 317 nm.

Large scale photolysis was carried out to isolated the photoproducts. 4-(3-Buten-
1-oxy)-2-trifluoromethylbenza1dehyde (50 mg, 0.20 mmol) was dissolved in freshly

distilled acetonitrile (15 mL) and irradiated in an immersion well with a medium pressure

166

mercury arc lamp through a Pyrex filter. The reaction progress was monitored by HPLC.
The reaction mixture was concentrated at reduced pressure and separated using
preparative TLC (hexane:ethyl acetate, 80:20) followed by HPLC (hexanezethyl acetate,
80:20). The products were collected at 13 minute from HPLC and identified by NMR
analysis as 4-formy1-2-trifluoromethyl-11-oxabicyclo[6.3.0]undeca-1,3,5-triene (Al-CF3-

C00 (4 mg, 8% yield).

4-Formyl-2-trifluoromethyl-ll-oxabicyclo[6.3.0]undeca-l,3,5-triene (Al-CF3-COt)

1H NMR (CDC13, 300 MHz, 6 ppm): 2.04 (qd, J = 10.44 and 8.24 Hz, 1H9), 2.19 (ddd, J

= 7.14, 6.49 and 6.04 Hz, 1H,), 2.42 (ddd, J = 7.14, 6.59 and 6.04 Hz, 1H7), 2.69 (m,

1H9»), 3.15 (m, 1H3), 4.13 (ddd, J = 8.79, 5.49 and 4.94 Hz, le), 4.34 (ddd, J = 8.79,

8.24 and 1.65 Hz, 11110.), 5.52 (d, J = 6.3 Hz, 1H2), 6.90 (dd, J=7.14 and 7.69 Hz, 1H5),

7.14 (C1, .1 = 6.3 HZ, 1H3) and 9.53 (S, lHaldehyde)-

UV: 317 nm.

4.5.4.1. Photochemistry of 4-formyl-2-trifluoromethyl-ll-oxabicyclo[6.3.0]undeca-

1,3,5-triene (Al-CF3-C0t)

167

 

hv, pyrex
acetonitrile,FiT

 

   

Al-CFB-COt Al-CFS-CBt

 

 

In an NMR tube, Al-CF3-COt (2.0 mg, 0.0082 mmol) was dissolved in

deuterated acetonitrile (0.75 mL). The sample was purged with argon for 15 minutes and
then irradiated with a medium pressure mercury arc lamp through a Pyrex filter sleeve.
Reaction progress was monitored by 1H NMR and HPLC. NMR analysis of the reaction
mixture showed the presence of l-formyl-2-trifluoromethyl-8-
oxatricyclo[7.2.0.09'5]undeca-2,10-diene (Al-CF3-CBt). The thermally unstable

photoproduct in the NMR scale reaction of Al-CF3 was found to be Al-CF3-CBt.

1-Formyl-2-trifluoromethyl-8-oxatricyclo[7.2.0.0”5]undeca-2,10-diene (Al-CF3-CBt)

1H NMR (CDC13, 300 MHz, 5 ppm): selected signals: 4.24 (t, J = 6.59 Hz, 2H7), 6.43 (d,

J = 2.75 Hz, 1H“), 6.51 (d, J = 2.75 Hz, lHlo), 6.82 (m, 1H3) and 9.45 (s, lHatdehydc).

168

4.5.5. Photolysis of 4-(3-buten-l-oxy)-2-methylbenzonitrile

In an NMR tube, 4-(3-buten-1-oxy)-2-methylbenzonitrile (2.0 mg) was dissolved
in deuterated acetonitrile (0.75 mL, 1.43 x 10’2 M). The sample was purged with argon
for 15 minutes and then irradiated with a medium pressure mercury arc lamp through a
Pyrex filter sleeve. Reaction progress was monitored by 1H NMR and HPLC. NMR
analysis of the reaction mixture showed the presence of several photoproducts after 14

days of irradiation.

 

 

.. 0 re -
acetonitrile,F1T

CN-CH3

 

CN-CH3-COa CN-CHS-CBt

 

 

4-(3-Buten-1-oxy)-2-methylbenzonitrile (2.0 mg, 0.0053 mmol) was dissolved in

deuterated acetonitrile (0.75 mL, 1.43 x 10'2 M) inside a quartz test tube. The sample was
purged with argon for 20 minutes and then irradiated using a Rayonet reactor with 254
nm light bulbs. Reaction progress was monitored by time resolved ‘H NMR and HPLC.
NMR analysis of the reaction mixture showed the presence of several photoproducts on

the complete depletion of reactant after 18 hours of irradiation.

In an NMR tube, 4-(3-buten-1-oxy)-2-methylbenzonitrile (2.0 mg, 0.0053 mmol)

was dissolved in deuterated acetone (0.75 mL, 1.43 x 10'2 M). The sample was purged

169

with argon for 15 minutes and then irradiated with a medium pressure mercury arc lamp
through a 313 nm filter solution. Reaction progress was monitored by 1 H NMR and
HPLC. NMR analysis of the reaction mixture showed the presence of several
photoproducts after 24 hours of irradiation. Large scale photolysis was carried out to
isolate the photoproducts. 4-(3-Buten-1-oxy)-2-methylbenzonitrile (183 mg) was
dissolved in freshly distilled acetone (50 mL) and irradiated with a medium pressure
mercury arc lamp through a 313 nm filter solution. The reaction progress was monitored
by HPLC. The reaction mixture was concentrated at reduced pressure and separated using
HPLC (hexane:ethy1 acetate, 80:20). Two major products were collected at 8 minutes and
3 minutes from HPLC and identified by NMR analysis as 4-cyano-3-methyl-11-
oxabicyclo[6.3.0]undeca-l,3,5-triene (CN-CH3-C0a) (9 mg, 5% yield) and 1-cyano-2-
methyl-8-oxatricyclo[7.2.0.09’5]undeca-2,10—diene (CN-CH3-CBt) (2 mg, 1% yield),
respectively. The CN-CH3—COa/CN-CH3-CBt ratios were measured by NMR analysis

to be 1:2, 5:1 and 3:1 with the light source of >300 nm, 254nm, and 313 nm, respectively.

a. 4-Cyano-3-methyl-ll-oxabicyclo[6.3.0]undeca-l,3,5-triene (CN-CH3-C0a)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.80 (dddd, J = 12.09, 9.34, 6.59 and 6.04 Hz,
1H9), 2.17 (s, 3H), 2.33 (dddd, J = 12.09, 11.54, 10.44 and 8.24 Hz, 1H9), 2.39 (dddd, J =
9.89, 9.34, 4.4 and 1.65 Hz, 1H7), 2.45 (dddd, J = 9.34, 9.0, 4.4 and 1.65 Hz, 1H7), 3.20
(m, 1H3), 4.18 (ddd, J = 8.79, 8.24 and 3.3 Hz, lHtov), 4.29 (ddd, J = 8.79, 6.59 and 6.04

Hz, 1Hlo), 5.25 (s, 1H2), 5.77 (br (1, J=l3 Hz, 1H5), 6.77 (dt, J=13 and 4.4 Hz, 1H6).

170

UV: 310 nm.

b. l-Cyano-2-methyl-8-oxatricyclo[7.2.0.0”5]undeca-2,10-diene (CN-CHS-CBt)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.89 (dtd, J = 12.64, 6.04 and 1.65 Hz, 1H6), 1.95
(d, J = 1.65 Hz, 3Hmyl), 2.09 (ddd, J = 15.9, 5.1, and 4.3 Hz, 1H4), 2.16 (dddd, J =
12.64, 7.69, 6.04 and 1.65 Hz, 1H6), 2.21 (m, 1H5), 2.30 (m, 1H4), 3.81 (ddd, J = 8.24 Hz,
7.14 Hz, 1H7), 3.93 (ddd, J = 8.24 Hz, 3.29 Hz, 1H7), 5.48 (t quartet, J = 6.04 Hz and

1.65 Hz, 1H3), 6.17 (d, J = 2.8Hz, 1H”), 6.77 (d, J = 2.8 Hz, lHlo).

4.5.6. Photolysis of 4-(3-buten-l-oxy)-2-methoxylbenzonitrile

4-(3-Buten-l-oxy)-2-methoxybenzonitrile (2.7 mg, 0.013 mmol) was dissolved in
deuterated acetonitrile (0.75 mL, 1.8 x 10'2 M). The sample in a quartz test tube was
purged with argon for 20 minutes and then irradiated using a Rayonet reactor with 254
nm lamps. Reaction progress was monitored by 1H NMR and HPLC. NMR analysis of
the reaction mixture showed the presence of several photoproducts on the complete

depletion of reactant after 18 hours of irradiation.

In an NMR tube, 4-(3-buten-l-oxy)-2-methoxybenzonitri1e (2.7 mg, 0.013 mmol)

was dissolved in deuterated acetone (0.75 mL, 1.8 x 10'2 M). The sample was purged

171

 

with argon for 15 minutes and then irradiated with a medium pressure mercury arc lamp
through a 313 nm filter solution. Reaction progress was monitored by time resolved 1H
NMR and HPLC. NMR analysis of the reaction mixture showed the presence of several

photoproducts after 30 hours of irradiation.

 

 

9H3
0
hv, rex
.... Q 0% F”. -
acetonltnle,RT NC

CN-OCHS

 

CN-OCHS-COa CN-OCH3-CBt

109 76
l 5

 

 

 

 

 

 

 

CN-OCH3-LCBa

 

 

In an NMR tube, 4-(3-buten-1-oxy)-2-methoxybenzonitrile (2.7 mg) was
dissolved in deuterated acetonitrile (0.75 mL, 1.8 x 10'2 M). The sample was purged with
argon for 15 minutes and then irradiated with a medium pressure mercury arc lamp
through a Pyrex filter sleeve. Reaction progress was monitored by 1H NMR and HPLC.
NMR analysis of the reaction mixture showed the presence of several photoproducts after
20 hours of irradiation. Large scale photolysis was carried out to isolate the
photoproducts. 4-(3-Buten-l-oxy)-2-methoxybenzonitrile (177 mg) was dissolved in

freshly distilled acetonitrile (50 mL) and irradiated in an immersion well with a medium

172

pressure mercury arc lamp through Pyrex filter sleeve. After 28 hours, the reaction
progress was monitored by HPLC. The reaction mixture was concentrated at reduced
pressure and separated using preparative TLC (hexanezethyl acetate, 80:20) and HPLC
(hexanezethyl acetate, 80:20). The reaction mixture was concentrated at reduced pressure
and separated using preparative TLC (hexanezethyl acetate, 80:20) and HPLC
(hexanezethyl acetate, 80:20). Two products came out at 9 minutes from HPLC.

One photoproduct was isolated and identified as 4-cyano-3-methoxy-11-
oxabicyclo[6.3.0]undeca-l,3,5-triene (CN-OCH3-C0a) (9 mg, 5%) while the other
photoproduct at 9 minutes in the mixture with CN-OCH3-C0a was identified as 11-
cyano-1-methoxy4-oxatricyclo[7.2.0.03'7]undeca-2, lO-diene (CN-OCH3-LCBa).
Another photoproduct collected at 6 minutes from HPLC was not stable thermally and
identified as l-cyano-2-methoxy-8-oxatricyclo[7.2.0.09'5]undeca-2,10-diene (CN-OCH3-
CBt). The ratios of CN-OCH3-C0a: CN-OCH3-CBt: CN-OCH3-LCBa were
measured by NMR analysis to be 8:22] and 10: 1 :1 with the light source of 254 nm and

313 nm, respectively.

a. 4-Cyano-3-methoxy-ll-oxabicyclo[6.3.0]undeca-l,3,5-triene (CN-OCH3-C0a)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.88 (ddt, J = 12.64, 6.59 and 6.04 Hz, 1H9), 2.24

(m, 1H9), 2.38 (dddd, J = 10.44, 5.49, 4.94, and 4.40 Hz, 1H7), 2.51 (dtd, J=17.58, 4.4

and 1.65 Hz, 1H7), 3.43 (m, 1H3), 3.77 (s, 3HMc), 4.31 (ddd, J=8.79, 8.24 and 3.85 Hz,

173

 

 

lHlo), 4.39 (ddd, J=9.34, 8.79 and 6.04 Hz, lHlo), 5.32 (s, 1H2), 5.75 (dt, J=12.09 and

4.40 Hz, 1H6), 5.83 (br (1, J=12.64, 1H5).

UV: 297 nm

b. 1-Cyano-2-methoxy.8-oxau-icyclo[7.2.o.o”‘]undeca-2,lo-diene (CN-OCH3-CBt)

1H NMR (CDC13, 300 MHz, 5 ppm): selected signals: 3.60 (s, 3Hmcmyl), 3.98 (ddd, 1H7),

 

4.15 (ddd, 1H7), 4.65 (dd, J = 6.59 and 2.75 Hz, 1H3), 6.18 (d, J = 2.75 Hz, 1H”), 6.29

(d, J = 2.75 Hz, lHlo).

c. 1l-Cyano-l-methoxy-4-oxatricyclo[7.2.0.03’7]undeca-2,10-diene (CN-OCH3-

LCBa)

1H NMR(CDC13, 300 MHz, 5 ppm): selected signals: 4.92 (s, 1H2) and 6.9 (d, J=1.0,

1H10)-

174

 

4.5.7. Photolysis of 4-(3-buten-l-oxy)-2-fluorobenzonitrile

 

 

F
hv, rex
No Q o/“\——-— F”. »
acetomtnle,RT

CN-F

 

 

CN-F-CBt CN-F-CBa

 

 

In an NMR tube, 4-(3-buten-l-oxy)-2-fluorobenzonitrile (2.0 mg, 0.01 mmol) was
dissolved in deuterated acetonitrile (0.75 mL, 1.39 x 10'2 M). The sample was purged
with argon for 15 minutes and then irradiated with a medium pressure mercury arc lamp
through a Pyrex filter sleeve. Reaction progress was monitored by 1H NMR and HPLC.
NMR analysis of the reaction mixture showed the presence of several photoproducts after

14 days of irradiation.

In an NMR tube, 4-(3-buten-l-oxy)-2-fluorobenzonitrile (2.0 mg, 0.01 mmol) was
dissolved in deuterated acetonitrile (0.75 mL, 1.39 x 10'2 M). The sample was purged
with argon for 15 minutes and then irradiated with a medium pressure mercury arc lamp
through a 313 nm filter solution. Reaction progress was monitored by 1H NMR and
HPLC. NMR analysis of the reaction mixture showed the presence of several
photoproducts after 24 hours of irradiation. Large scale photolysis was carried out to

isolate the photoproducts. 4-(3-Buten-l-oxy)-2-fluorobenzonitrile (166 mg, 0.87 mmol)

175

 

 

was dissolved in freshly distilled acetone (50 mL) and irradiated with a medium pressure
mercury arc lamp through a 313 nm filter solution. The reaction progress was monitored
by HPLC. The reaction mixture was concentrated at reduced pressure and separated using
preparative TLC (hexanezethyl acetate, 80:20) and HPLC (hexane:ethyl acetate, 80:20)
after 48 hours of irradiation. One photoproduct was collected at 9.5 minute using HPLC
and identified as 1-cyano-2-fluoro—8-oxatricyclo[72.0.08”5 ]undeca-2,lO-diene (CN-F-
CBt) (25.1 mg, 15%). Another photoproduct was collected at 5.5 minutes from HPLC
and identified as l-cyano-l 1-fluoro-8-oxatricyclo[7.2.0.095]undeca-2, lO—diene (CN-F-

CBa) (14.2 mg, 8.6%).

The ratios of CN-F-CBt: CN-F-CBa were measured by NMR analysis to be 1.6:]

and 1:1.8 ratio with the light sources of >300 nm and 313 nm, respectively.

a. l-Cyano-2-fluoro-8-oxatricyclo[7.2.0.0”’]undeca-2,10-diene (CN-F-CBt)

1H NMR(CDC13, 300 MHz, 8 ppm): 1.96 (ddd, J = 11.54, 8.24 and 3.85 Hz, 2H6), 2.22

(dddd, J = 15.38, 9.89, 6.04 and 3.30 Hz, 1H4), 2.28 (dddd, J = 15.38, 8.79, 6.04 and 3.85
Hz, 1H4), 2.44 (m, 1H5), 3.97 (ddd, J = 9.34, 8.24 and 7.69 Hz, 1H7), 4.18 (ddd, J = 9.34,
8.24 and 3.30 Hz, 1H7), 5.33 (ddd, J=14.28, 7.14 and 2.75 Hz, 1H3), 6.25 (d, J = 2.75 Hz,

1H”) and 6.33 (t, J = 2.75 HZ, Him).

176

 

13C-NMR (CDC13, 75 MHz, 8 ppm): 22.10(d), 28.39, 38.65, 5168,6124, 67.66,

102.28(d), 107.5, 135.17, 141.39 and 148.08.

GC-MS (m/z): 39, 41, 51, 55(Base), 63, 69, 75, 83, 89, 95, 107, 115, 122, 135, 140, 162,

172 and 191(M+').

b. l-Cyano-ll-fluoro-8-oxatricyclo[7.2.0.09’5]undeca-2,10-diene (CN-F-CBa)

1H NMR (CDC13, 300 MHz, 8 ppm): 1.93 (ddd, J = 12.09, 9.34 and 2.20 Hz, 11-16), 2.00
(ddd, J = 12.09, 4.40 and 3.85 Hz, 1H6), 2.24 (ddd, J = 18.13, 6.04 and 2.75 Hz, 1H4),
2.38 (ddd, J = 18.13, 6.59 and 2.20 Hz, 1H4), 2.51 (m, 1H5), 3.95 (ddd, J = 8.79, 8.24 and
7.14 Hz, 1H7), 4.18 (ddd, J = 9.34, 8.24 and 3.30 Hz, 1H7), 5.11 (d, J = 8.79 Hz, lHlo),

5.72 (dd, J = 9.89 Hz and 2.75Hz, 1H2) and 5.93 (ddd, J = 9.89, 6.59 and 2.2 Hz, 1H3).

lBC-NMR (CDC13, 75 MHz, 8 ppm): 24.18, 27.97, 37.28, 37.39, 66.76, 77.13, 107.46,

107.54, 120.13(d), 129.20 and 150.59(d).

GC-MS (m/z): 39.1, 55.1(Base), 63.0, 75.0, 83, 95.0, 109.0, 122.0, 135.0, 148.0, 164.0,

172.0 and 191(M”).

177

 

F 8

254 / rtz 1° 9 7 6
NC 0 o/—\= nrri 6.1a , 5
acetonrtnle,RT NC F 3 o

2 4

 

CN-F CN-F-LCBa

 

 

4-(3-Buten-l-oxy)-2-fluorobenzonitrile (8.0 mg, 0.042 mmol) was dissolved in
deuterated acetonitrile (3.0 mL, 1.39 x 10'2 M). The sample was purged with argon for 15
minutes and then irradiated by a Rayonet reactor with 254 nm lamps. Reaction progress
was monitored by 1H NMR and HPLC. NMR analysis of the reaction mixture showed the
presence of several photoproducts on the complete depletion of reactant after 30 hours of
irradiation. One product in the mixture was identified as 11-cyano-1-fluoro—4-

oxatricyclo[7.2.0.03’7]undeca-2,lO-diene (CN-F-LCBa).

4.5.7.1. Thermal chemistry of l-cyano-2-fluoro-8-oxatricyclo[7.2.0.0”5]undeca-Z,10-

diene (CN-F-CBt)

 

 

00300 F 8
, 1o

CN-F-CBt CN-F-COt

 

 

 

178

 

1—Cyano-2-fluoro-8-oxatricyclo[7.2.0.09’5]undeca-2,lO—diene (CN-F-CBt) (1.1
mg, 0.0058 mmol) in deuterated methanol (1 mL) was heated at 50 °C in the silicone oil
bath for 12 hours. The reaction was monitored by NMR and HPLC. The ring opening

product was identified as 4—cyano-5-fluoro—11-oxabicyclo[6.3.0]undeca—1,3,5-triene (CN-

F-COt).

4-Cyano-5-fluoro-ll-oxabicyclo[6.3.0]undeca-l,3,5-triene (CN-F-COt)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.85 (dddd, J = 19.04, 7.32, 6.84 and 5.37 Hz,
1H9), 2.23(dtd, J = 20.02, 7.81 and 4.40 Hz, 1H9), 2.43 (ddd, J = 16.6, 10.74, 5.86 and
2.93 Hz, 1H7), 2.55 (dddd, J = 16.6, 6.35, 5.86 and 2.93 Hz, 1H7), 3.07 (m, 1H3), 4.26
(ddd, J = 8.79, 7.81 and 4.88 Hz, le), 4.30 (ddd, J = 8.79, 7 .81 and 6.86 Hz, lHlo), 5.40

(d, J = 7.32 Hz, 1H2), 5.70 (dt, J = 23.93 and 5.86 Hz, 1H6), 6.86 (d, J = 7.32 Hz, 1H3).

UV: 320 nm.

179

4.5.7.2. Thermal chemistry of l-cyano-l1-t'luoro«-8-oxatricyclo[7.2.0.0"’5 lundeca-2,10-

diene (CN-F-CBa)

 

 

 

6 7 9
00300 5 3
, 1o
50°C NC 0
F 2
CN-F-CBa CN-F-COa

 

 

l-Cyano-l 1-f1uoro-8-oxatricyclo[7.2.0.09'5]undeca-2, lO-diene (CN-F-CBa) (2.2
mg, 0.012 mmol) in deuterated methanol (1 mL) was heated at 50 °C in the silicone oil
bath for 24 hours. The reaction was monitored by NMR and HPLC. The ring opening

product was identified as 4-cyano-3-fluoro—1l-oxabicyclo[6.3.0]undeca-1,3,5-triene (CN-

F-COa).

4-Cyano-3-fluoro-l1oxabicyclo[6.3.0]undeca-l,3,5-triene (CN-F-COa)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.91 (dddd, J = 12.09, 12.64, 4.94 and 4.39 Hz,

1H9), 2.28 (dddd, J = 12.09, 8.24, 7.69 and 4.39 Hz, 1H9), 2.47 (ddt, J = 10.44, 6.04 and

1.65 Hz, 1H7), 2.55 (dtd, J = 15.93, 3.86 and 1.65 Hz, 1H7), 3.35 (m, 1H3), 4.32 (ddd, J =

180

8.79, 7.69 and 4.39 Hz, lHlo), 4.41 (td, J = 8.79 and 6.59 Hz, 1H10v), 5.31 (d, J = 9.34 Hz,

1H2), 5.76 (dd, J = 12.64 and 4.94 Hz, 1H5) and 5.98 (dt, J = 12.64 and 5.49 Hz, 1H5).

13C-NMR (CDC13, 75 MHz, 5 ppm): 30.88, 31.12, 40.08, 70.59, 89.61, 90.11, 103.92,

120.45 and 132.07.

UV: 298 nm

4.5.8. Photolysis of 4-(3-buten-l-oxy)-2-trifluoromethylbenzonitrile

 

    

 

 

F30 ‘ 5 6 10 9 7 6
FL hv pyrex F3° "j J; / 5
— ' > + 0
NC 0 O acetonitrile,RT NC ! " 7 NC F3C 2 3 4
11 10
CN-CF3 cu-c|=3.cat CN-CFS—LCBa

 

 

In an NMR tube, 4-(3-buten-l-oxy)-2-trifluorofluoromethylbenzonitrile (2.1 mg,

0.0087 mmol) was dissolved in deuterated acetonitrile (0.75 mL, 1.16 x 10'2 M). The
sample was purged with argon for 15 minutes and then irradiated with a medium pressure
mercury arc lamp through a Pyrex filter sleeve. Reaction progress was monitored by 1H
NMR and HPLC. NMR analysis of the reaction mixture showed the presence of several

photoproducts after 36 hours of irradiation.

18]

4-(3-Buten-1-oxy)-2-trifluoromethylbenzonitrile (8.4 mg, 0.035 mmol) was
dissolved in deuterated acetonitrile (3.0 mL, 1.16 x 10'2 M). The sample was purged with
argon for 15 min and then irradiated by a Rayonet reactor with 254 nm lamps. Reaction
progress was monitored by 1H NMR and HPLC. NMR analysis of the reaction mixture
showed the presence of several photoproducts on the complete depletion of reactant after

12 hours of irradiation.

In an NMR tube, 4-(3-buten-1-oxy)-2-trifluoromethylbenzonitrile (2.0 mg, 0.0083
mmol) was dissolved in deuterated acetonitrile (0.75 mL, 1.5 x 10'2 M). The sample was
purged with argon for 15 minutes and then irradiated through a 313 nm filter solution.
Reaction progress was monitored by time resolved 1H NMR and HPLC. NMR analysis of
the reaction mixture showed the presence of several photoproducts after 22 hours of

irradiation.

Large scale photolysis was carried out to isolate the photoproducts. 4—(3-buten-l-
oxy)—2-trifluoromethylbenzonitrile (148 mg, 0.61 mmol) was dissolved in freshly
distilled acetonitrile (50 mL) and irradiated through a 313 nm filter solution. The reaction
progress was monitored by HPLC. The reaction mixture was concentrated at reduced
pressure and separated using preparative TLC HPLC (hexanezethyl acetate, 80:20) and

HPLC (hexanezethyl acetate, 80:20) after 24 hours of irradiation.

182

One photoproduct was collected at 11 minutes using HPLC and identified as l-
cyano-2-trifluoromethyl-8-oxatricyclo[7.2.0.09'5]undeca-2,10-diene (CN-CF3-CBt) (8
mg, 5.4%). Another photoproduct was collected at 7 minutes from HPLC and identified
as 1 1-cyano-1-trifluoromethyl-4-oxatricyclo[7.2.0.03’7]undeca-2,10-diene (CN-CF3-
LCBa) (6 mg, 4%).

The ratios of CN-CF3-CBt: CN-CF3-LCBa were measured by NMR analysis
to be 1: 10, 1:10 and 1:1 ratio with the light sources of >300 nm, 254 nm and 313 nm,

respectively.

a. l~Cyano-2-trifluoromethyl-8-oxatricyclo[7.2.0.09'5]undeca-Z,10-diene(CN-CFB-

CBt)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.85 (ddd, J = 9.89, 9.34 and 7.14 Hz, 1H6), 2.06
(ddd, J = 14.28, 7.14, and 3.85 Hz, 1H4), 2.34 (ddd, J = 9.89, 6.59 and 3.30 Hz, 1H6),
2.49 (m, 1H5), 2.53 (ddd, J = 15.38, 8.79, and 3.85 Hz, 1114), 4.02 (ddd, J = 8.79 and 3.85
Hz, 1H7), 4.19 (ddd, J = 8.79, 8.24 and 7.69 Hz, 1H7), 6.22 (d, J = 2.75 Hz, 1H“), 6.31

((1, J = 2.75 HZ, 1H10) and 6.51 (111, 1H3).

l3C-NMR (CDC13, 75 MHz, 5 ppm): 24.57, 28.33, 37.64, 67.11, 89.59, 131.55(q),

136.35 and 140.54.

183

b. 1l-Cyano-1-trifluoromethyl-4-oxatricyclo[7.2.0.03’7]undeca-2,lO—diene (CN-CF3-

LCBa)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.32 (m, J = 11.54 and 7.69 Hz, 1H6), 1.73 (dddd, J
= 11.54, 8.79, 7.69 and 2.2 Hz, 1H6), 2.22 (ddd, J = 15.93, 6.59, and 1.65 Hz, 1H3), 2.27
(ddd, J = 15.93, 7.14 and 1.65 Hz, 1H3), 2.33 (m, H7), 3.35 (dd, J = 5.49 and 1.65 Hz,
1H9), 4.03 (ddd, J = 8.79, 8.24 and 7.14 Hz, 1H5), 4.30 (ddd, J = 8.79 and 8.24 Hz, 1H5),

4.93 (d, H = 3 Hz, 1H2) and 6.94 (br s, le).

UV: 267.

4.5.8.1. Thermal chemistry of l-cyano-2-trifluoromethyl-8-oxatricyclo[7.2.0.0”5]

undeca-2,10-diene (CN-CFB-CBt)

 

 

6 7 9
coaoo F30 3
, 10
100°C ”0 o

CN-CF3-CBt CN-CF3-COt

 

 

 

184

l -Cyano—2-trifluoromethyl-8-oxatricyclo[7.2.0.09'5]undeca-2,10—diene (CN-CFB—
CBt) (2.4 mg, 0.01 mmol) in deuterated methanol (1 mL) was heated at 100 °C in the
silicone oil bath for 24 hours. The reaction was monitored by NMR and HPLC. The ring

opening product was identified as 4-cyano-5-trifluoromethyl-1 1-

oxabicyclo[6.3.0]undeca-1 ,3,5-triene (CN-F-COa).

4-Cyano-5-trifluoromethyl-1l-oxabicyclo[6.3.0]undeca-l,3,5-triene (CN-CF3-COt)
1H NMR (CDC13, 300 MHz, 5 ppm): seleted signals: 5.16 (d, J = 6.59 Hz, 1H2), 6.41 (t,

J = 7.69 Hz, 1H6) and 6.54 (d, J = 6.59 Hz, 1H3).

4.5.9. 6-(3-Buten-l-oxy)-1-tetralone

 

 

O/_\= hv, pyrex ’
O acetonitrile,RT

1T

 

 

 

185

In an NMR tube, 6-(3-Buten-l-oxy)-1-tetralone (2.1 mg, 0.01 mmol) was
dissolved in deuterated acetonitrile (0.75 mL, 1.29 x 10'2 M). The sample was purged
with argon for 15 minutes and then irradiated with a medium pressure mercury arc lamp
through a Pyrex filter sleeve. Reaction progress was monitered by time resolved 1H NMR
and HPLC. After 8 hours of irradiation, NMR analysis of the reaction mixture showed the

presence of several photoproducts.

Large scale photolysis was carried out to isolate the photoproducts. 6—(3-Buten-l-
oxy)-1-tetralone (182 mg, 0.84 mmol) was dissolved in freshly distilled acetonitrile (50
mL) and irradiated in an immersion well with a medium pressure mercury arc lamp
through a Pyrex filter. The reaction progress was monitored by HPLC. The reaction
mixture was concentrated at reduced pressure and separated using preparative TLC
(hexanezethyl acetate, 80:20) followed by HPLC (hexane:ethyl acetate, 80:20), after 8

hours of irradiation.

One photoproduct collected at 13 minutes from HPLC was identified as 15-oxa-
tetracyclo[10, 3, 0, 0"8, 03's]pentadeca-2,9-diene-7-one ('IT-CBa) (13 mg, 7.1%).
Another photoproduct collected at 10 minutes from HPLC was identified as 15-oxa-
tricyclo[10, 3, 0, 03’8]pentadeca-1, 3, 9-triene-7-one ('IT-COa) (2 mg, 1.1%). The other
photoproduct collected at 9 minutes from HPLC was identified as 15-oxa—tetracyclo[10,

3, 0, 01'"), 04'9]pentadeca-2, 4-diene-5-one (TT-CHt) (~l mg).

186

Three products were identified as TT-CBa, TT-COa, TT-CHt in 10:2:1 ratio.

a. 15-Oxa-tetracyclo[10, 3, 0, 0"“, 0”]pentadeca-2,9-diene-7-one (TT-CBa)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.60 (dddd, J = 13.18, 9.77, 9.27 and 8.79 Hz,
1H13), 1.81 (m, J = 5.85 Hz, 2H5), 1.91 (dddd, J = 13.18, 9.77 and 8.79 Hz, 1H”), 1.92
(m, 1H12), 2.17 (ddd, J = 8.79, 6.35 and 5.86 Hz, 1H4), 2.23 (dddd, J = 8.79, 6.35, 5.86
and 2.1 Hz, 1H4), 2.36 (m, J = 6.9 and 1.8 Hz, 2H“), 2.48 (t, J = 5.86 Hz, 2116), 4.04
(ddd, J = 15.63, 9.77 and 1.95 Hz, 1H14), 4.12 (ddd, J = 15.63, 8.79 and 1.95 Hz, 1H14~),
5.69 (dd, J = 9.9 and 2.4 Hz, 1H9), 5.83 (d, J = 2.1 Hz, 1H2) and 5.96 (ddd, J = 9.9, 6.9

and 1.8, lHlo).

13C-NMR (CDC13, 75 MHz, 5 ppm): 23.80, 24.14, 26.16, 26.45, 33.07, 38.88, 39.78,

42.25, 68.04, 125.16, 127.39, 131.29, 155.45 and 208.01.

b. lS-Oxa-tricycloIlO, 3, 0, 0”]pemadeca-1, 3, 9-triene-7-one (Tr-C03)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.80 (J = 15.93, 9.89, 6.04 and 3.3 Hz, 1H13), 1.91

(J = 15.93 and 6.59 Hz, 1H13), 1.95 (J = 9.89, 8.79, 6.59 and 4.94 Hz, 1H“), 2.15 (J =

9.89, 7.69 and 3.85 Hz, 1H“), 2.24 (m, J = 5.49 and 1.65 Hz, 1H4), 2.31 (m, 1H4), 2.40

(quintet, J = 5.49 Hz, 2H5), 2.49 (dd, J = 5.49 and 4.94 Hz, 2H6), 3.1 (m, 1H12), 4.21 (td, J

187

= 8.24 and 3.30 Hz, 1H”), 4.31 (td, J = 8.79 and 6.59 Hz, 1H14), 5.38 (s, 1H2), 5.86 (dt, J

= 12.6 and 4.5 Hz, lHlo) and 6.21 (br d, J = 12 Hz, 1H9).

UV: 309.

c. 15-Oxa-tetracyclo[10, 3, 0, 0"”, 0”]pentadeca-2, 4-diene-5-one (TT-CHt)

1H NMR (CDC13, 300 MHz, 5 ppm): 1.69 (dddd, 1H13). 1.96 (dddd, 1H13). 1.98 (tt, 2H7),
2.05 (t, 2H3), 2.09 (t, 2H"), 2.42 (t, 2116), 2.94 (tt, lle), 3.11 (br t, le), 4.17 (dt, 2H”),

5.53 (d, J = 10 Hz, 1H2) and 6.62 (d, J = 10 Hz, 1H3).

UV: 261

4.5.10. 6-(3-Buten-1-oxy)-l-chromonone

 

  
    

 

O
O O/—\= hv, pyrex >
O acetonitrile,RT

CR

 

188

In an NMR tube, 6—(3-buten-1-oxy)-l—chromonone (2.1 mg, 0.01 mmol) was
dissolved in deuterated acetonitrile (0.75 mL, 1.28 x 10'2 M). The sample was purged
with argon for 15 minutes and then irradiated with a medium pressure mercury arc lamp
through a Pyrex filter sleeve. Reaction progress was monitored by 1H NMR and HPLC.
After 2 hour of irradiation, NMR analysis of the reaction mixture showed the presence of

several photoproducts.

Large scale photolysis was carried out to isolate the photoproducts. 6-(3-buten-l-
oxy)-1-chromonone (170 mg, 0.78 mmol) was dissolved in freshly distilled acetonitrile
(50 mL) and irradiated in an immersion well with a medium pressure mercury arc lamp
through a Pyrex filter. The reaction progress was monitored by HPLC. After 8 hours of
irradiation, the reaction mixture was concentrated at reduced pressure and separated using

preparative TLC (hexanezethyl acetate, 80:20) and HPLC (hexanezethyl acetate, 80:20).

One photoproduct collected at 22 minutes from HPLC was identified as 4,15-
dioxa-tn'cyclo[10, 3, 0,03'8 ]pentadeca-l, 3, 9-triene-7-one (CR-COa) (10 mg, 5.3%). The
other photoproduct collected at 12 minutes from HPLC was identified as 8,15-dioxa-
tetracyclo[10, 3, 0, 0""), 04'9]pentadeca-2, 4-diene-5-one (CR-CHt) (~l mg). The ratio of

two product (CR-COaI CR-CHt) was 10: 1.

a. 4,15-Dioxa-tricyclo[10, 3, 0,0”1pentadeca-1, 3, 9-triene-7-one (CR-COa)

189

1H NMR (CDC13, 300 MHz, 5 ppm): 1.84 (ddt, J = 12.40, 6.26 and 5.95 Hz, 1H13). 2.24
(dddd, J = 12.40, 6.59, 6.22 and 4.3 Hz, 11113). 2.38 (dtd, J = 10.44, 6.51 and 4.42 Hz,
1H“), 2.42 (td, J = 15.31 and 3.85 Hz, 1H6), 2.51 (m, J = 10.44, 1H“), 2.77 (td, J = 15.31
Hz and 3.2 Hz, 1H5), 3.37 (m, 1H12), 4.35 (t, J = 7.8 Hz, 2H5), 4.38 (td, J = 8.54 and 3.30
Hz, 1H”), 4.47 (td, J = 8.54 and 6.59 Hz, 1H14). 5.39 (s, 1H2), 5.83 (dt, J = 12.5 and 4.5
Hz, 1Hno) and 6.22 (br (1, J = 12.5 Hz, 1H9).

UV: 297

b. 8,15-Dioxa-tetracyclo[10, 3, 0, 0"”, 0"]pentadeca-2, 4-diene-5-one (CR-CHt)

1H NMR (CDC13, 300 MHZ, 5 ppm): 1.77 (dddd, 1H3), 2.04 (dddd, 1115), 2.23 (dt,
2H6), 2.54 ((11, 1H”), 2.64 (dt, 1H”), 2.97 (It, 1H12), 3.24 (br 1, lHlo), 4.18 ((11, 2H14),

4.46 (m, 2H7), 5.38 (d, J = 10 Hz, 1H2) and 6.59 (d, J = 10 Hz, 1H3).

4.6. Computational Analysis

The ground state and excited triplet state geometry and energy of the
photoreactants, intermediates and photoproducts were obtained using Spartan. Directions
of dipole moment for photoreactants in the ground state and excited triplet state were
calculated. The ab initio calculations were carried out in the level of (U )HF/6-3 16”

using Spartan (version 5.0) on Silicone Graphics computers of SGI Indigo workstations.

190

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194