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THE REAGEON OF TRIMETHOXYEOROXENE WITH
SOME ARYL GRIGNARD REAGENTS

Times}: for “:0 Degree 0‘; M. 5.

v v NM! nag-1 ~3ng gun. may? ;
MECflflAL‘: 3:2.th u'fiigaimd

Thoma: Faul E’ovkock

1957

THESIS
Q. l

LIBRARY

Michigan State
University

 

 

 

MICHIGAN STATE UNIVERSITY
W

EAST LANST NG, MICHIGAN

THE REACTION OF TRIMETHOXYBOROXINE WITH SOME
ARYL GRIGNARD‘REAGENTS

By

Thomas Paul Povlock

A THESIS

Submitted to the College of Science and Arts of Michigan
State University of Agriculture and Applied Science
in.partial fulfillment of the requirements
for the degree of

MASTER OF SCIENCE

Department of Chemistry

195 7

4-2”.3-3'

@- 5W7

ACKNOWLEDGMENT

The author wishes to express his sincere
appreciation to Dr. w. T. Lippincott, for the
encouragement, aid, and guidance which he so
generously gave during the course of the
investigation and preparation of this thesis.

\’ V \I \I \ ‘ \
'X‘fi'znnc-n-k *tit’r

ii

VITA

Name: Thomas Paul Povlock
Born: January 22, l93h in Salamanca, New York
Academic Career: Salamanca High School, l9h7-l9Sl

Kent State University,
Kent, Ohio, 1951-1955

Michigan State University,
East Lansing, Michigan, 1955‘1957

Degrees Held: B. S. - Kent State University, 1955

iii

Wu

4" .3

THE REACTION OF TRIMETHOXYBOROXINE WITH SOME
ARYL GRIGNARD REAGENTS

By

Thomas Paul Pavlock

AN ABSTRACT

Submitted to the College of Science and Arts of Michigan
State University of Agriculture and Applied Science
in partial fulfillment of the requirements
for the degree of

MASTER OF SCIENCE
Department of Chemistry

Year 1957

+V‘f

iv

ABSTRACT

The reaction of trimethoxyboroxine with some aryl Grignard reagents
was studied in an attempt to find a new method for the synthesis of
borinic acids. As a result of a study of the effect of temperature and
the effect of changing the mole ratio of trimethoxyboroxine to phenyl
magnesium bromide, it was found that the highest yield was obtained
when the reaction proceeds at 25°C. and with the mole ratio of boroxine
to Grignard of one to nine.

Using the reaction conditions developed for the preparation of
diphenylborinic acid, di(gftolyl), di(mrtolyl), di(pftolyl),
di(pfanisyl), di(pfchlorophenyl), di(g:naphthyl), and di(pfbiphenyl)
borinic acids were prepared. Of these acids, di(gftolyl), di(mftolyl),
diTpftolyl), and di(pfbiphenyl) have not been reported in the literature.
As a result of a study to determine the most successful method of
preparation and isolation of aminoethyl diphenylborinate, it was found
that the boronic acid must be completely removed before attempting the
esterification with ethanolamine.

Melting points, neutralization equivalents, and elemental analysis
were used to characterize the borinic esters. The melting points of

the boronic acids were correlated with the literature values.

TABLE OF CONTENTS

mmODUCTIONOOOOOOOOODOOIOOIOOOOOOIIOIIO...IIOIOOOOIOIOOOOOOOOOOO l

I. MOSGOOOOIOOIOOOIOOIOIO00...... ......... O ...... 00.0.00... 1

II. Historical.................................................
A. Borinic Acids........................................
B. Boronic Acids........................................
C. Trimethoxyboroxine...................................

P'WNN

MEMTALOOOODIOOOOIOI ........ C0.0000IOOOOOOCOOOOIOOOOOOIOI...

\‘l

I. Genera]- ProcedllrelOOOOOOIOOOOI.00....OOOOOOOOOOOOOOOOOOOOOI

x]

III ReagentSOOO0.00IOIIOIIIOOOIOOOOOOI.00'...OOOIOOOIOOIOOOOOOO

7
III. Preparation of Intermediates............................... 8
A. Preparation of Bromomesitylene....................... 8
B. Preparation of Trimethoxyboroxine.................... 9
C. Preparation of p-Chlorobromobenzene....... ........... 10

IV. Preparation of Grignard Reagents........................... 11
A. Genera—.1-ProcedllreOOOOOOo.0000....IIIOOOOOOOOOOOIOIIO. 11
B. Preparation of Grignard Reagent from p-Bromobiphenyl. 13

V} Reaction of the Aryl Magnesium Bromide with Trimethoxy-
boroxine................................................ 13
A. General Procedure.................................... 13
B. Effect of Temperature................................ 1h
C. Effect of Ratio Change............................... 16

VI. Isolation and Purification of Reaction Products............ 16
A. General Procedure for Borinates...................... 16
B. Other Methods........................................ 17
C. Purification of the Boronic Acids.................... 18

VII 0 AnalySis 0f the PrOduCtS . C O O O O C C C U C O I O O U 0 0 O O O O O O O O C O O O O O O D 0 20
A O Neutral-ization qulivalents O C O O O O C C O D U C U C . C O C O C O . O O 0 . O 20

B O Melting POintS . C O O O O O C O C O I C C I O I C C D O O C O O O C O O I O O C O O C C O . 20

C. Carbon, Nitrogen, and Hydrogen.Analysis.............. 21

D O Boron AnalySiS O O C C O O O O C O C O O O O C O C C O C C 0 O C C O C O O O O O O O O O O O 21
RmmTS‘UOCOOIOOIIOOIQOOOOOIOOOUCIOOOOUOI..COOIOCOOIOICOOOOOOOOO. 25
I. Effect of Temperature............................ ...... .... 25

II. Effect of Ratio of Boroxine to Grignard Reagent............ 25

vi

TABLE OF CONTENTS - Continued

III. Methods of Isolation........................... ........ .... 29
IV. Effect of Steric Factors................................... 31
V. Effect of Electrical Factors....... ....... ................. 31
DISCUSSION. ..... .................... ......... ... ....... .......... 3b
CONCLUSION........ ........... .................................... 39

BBLIOGRAPI-l-Ylooooooouooo ooooo 000000.000.0009000000000.00000000000 ho

vii

TABLE

I.

II.

III.

VI.

VII.

VIII.

LIST OF TABLES

Physical Constants of Borinic Acids........................
Yield of Aminoethyl Borinates..............................

Melting Points of Boronic Acids............................

. Melting Points and Neutralization Equivalents of Borinates.

. Analysis of Aminoethyl Borinates...........................

Temperature Effect in the Reaction of Trimethoxyboroxine
With Phenyl MagrleSj-um BromideOOOOO00.00.000.000.0.0.00.0...

Effect of Changing the Mole Ratio of Trimethoxyboroxine to
Pherml MagrleSj-um Bromide at 25 ......O..O..............C...

Comparison of Several Methods of Isolation of Borinic Acids

. Effect of Steric Factors...................................

. Effect of Electrical Factors................ ...... .........

viii

Page

6
15
19
23
2h

26

26
3O
32
32

LIST OF GRAPHS

GRAPH Page
I. Percent of Aminoethyl Diphenylborinate vs. Temperature 0C. 27

II. Percent of Aminoethyl Diphenylborinate vs. Mole Ratio of
Trimethoxyboroxine to Phenyl Magnesium Bromide............ 28

INTRODUCTION

I. Purpose

This study was undertaken to examine the reaction of trimethoxy-
boroxine with aryl Grignard reagents in order to find a new method for
synthesis of aryl borinic acids, and to improve the yields over the
currently used methods. In an attempt to elucidate a possible
mechanism for the reaction, a study of the effects of certain electri-
cal and steric factors was made.

From this study eight aryl borinic acids and eight aryl boronic
acids were obtained from the reaction of the appropriate Grignard
reagent with trimethoxyboroxine. Of the compounds prepared, four
borinic acids and one boronic acid have not been reported in the
literature. The yield of borinic acid isolated as the aminoethyl
ester was found to be approximately tws times that obtained from
currently used methods (1). The effect of temperature, ratio of tri-
methoxyboroxine to Grignard reagent, steric effects, and electrical
factors were studied along with the methods of isolation and purifi-
cation of the borinic acids and their esters. It was found that steric
factors and both electron donating and withdrawing groups decrease the
yield of borinic acid. A mechanism has been suggested to account for

some of these facts.

II. Historical
A. Borinic Acids

Aryl borinic acids, having the general formula RzBOH, have been
known since 189A when Michaelis (2) described the isolation of
diphenylborinic acid from the hydrolysis of the corresponding chloride.
Since the methods of isolation and characterization were doubtful, it
was not known whether or not the earlier workers had actually prepared
the reported compounds. In the case of the diphenylborinic acid, it
was not until 1955 that Letsinger (l) isolated and characterized this
acid. The yield of borinic acid was nonspecified in some of the early
work and when reported ranged from 20-hO percent.

Table I lists the alkyl and aryl borinic acids for which the melt-
ing or boiling points have been reported. Other borinic acids have
been prepared and isolated as an alkyl ester, but were not converted
to the acid. The boiling points of the acids which have been recorded
are actually those of the anhydride. Letsinger (1) has showed that
when diphenylborinic acid was distilled, the anhydride was recovered.

In some cases there are discrepancies in the reported physical
constants of the borinic acids as shown in Table I. Di(p:bromophenyl)
borinic acid is listed with two different melting points. Di(E-bipheny1)
borinic acid (6) is listed as melting above 300°C, but the isolated
compound was never proved to be the borinic acid. It was found as a
bydproduct in the preparation of the boronic acid and was assumed to

be the borinic acid.

Borinic acids have been prepared by use of one of the following
reactions, followed by hydrolysis.
l. Moist air oxidation of trialkylborines (R3B)(8).

2. Reaction of trialkylborines with iodine to prepare the di-
alkyliodoborines (9).

3. Reaction of trialkylborates [(RO)3B] or cyclic borates
ocHz

(RD-B: | ) with an excess of alkyl or aryl Grignard reagents
-' O-CH2

at -6o°c. (10).
Of these preparations, method 3 gives the best yields and is the most
widely used procedure.-

Two of the main difficulties in the preparation of borinic acids
anatheir separation from the boronic acid and the preparation of a
suitable derivative for characterization. Borinic esters obtained from
the above methods were separated from the boronic ester by use of a
method developed by Letsinger (1). This method consists of treating
the mixture of esters in ether solution with ammonia. The borinic
ester complexes with ammonia and precipitates from solution. The
complex is then treated with a solution of ethanolamine in water or
toluene to prepare the aminoethyl borinate. This ester is an excellent
derivative because it can be prepared easily, recrystallizes readily
from an ethanol-water mixture, melts sharply, analyzes well, and over

a period of months shows no sign of decomposing.

B. Boronic Acids
Boronic acids, having the general formula RB(OH)2, have received

far more attention in the literature than the borinic acids. In a

review article by Lappert (ll), seventy alkyl and aryl boronic acids
were reported along with their melting points. As in the case of the
borinic acids, there are reported different melting points for some of
the boronic acids (Table III).
The most important methods for the preparation of alkyl or aryl
boronic acids depends on one of the following procedures.
1. The addition of a metal alkyl or aryl to a trialkyl borate
and the hydrolysis of the boronic ester (12).
2. The addition of a metallic alkyl or aryl to a boron trihalide
to obtain the alkyl or aryl boron dihalide, which on hydrolysis
gives the boronic acid (13).
3. Anhydrous air oxidation of a trialkylborine to a boronic ester

and the hydrolysis of the latter (13).

C. Trimethoxyboroxine

Trimethoxyboroxine, I, is believed to be a six-membered ring

compound containing alternate boron and oxygen atoms with one methoxy
group attached to each boron atom. This structure was verified by
molecular weight determinations, elemental analysis, Raman spectra and

the solubility in anhydrous ether while one of its components, boric

anhydride, is insoluble as determined by Ogle (1h).
Quill and co-workers (15,16) studied the reaction of trimethoxy-
boroxine with alcohols and aryl amines. The reaction with alcohols is

illustrated in the following equation:

6ROH . (CHBOBO)3 -———e» 3(Bo)2B—OCH3 L 3H20

The following reaction illustrates the reaction of trimethoxyboroxine

with aniline:

OCH3 ooh,
T
B.\ B
0/ o 0/ \o
2(CH30BO)3 + <:::>>NH2 -—-ss 1 I T I
HSCO-B B - N - B B-OCH3
\O/ ‘ \O/

O + 2CH30H

TABLE I

PHYSICAL CONSTANTS OF BORINIC ACIDS

l

 

 

 

r

 

 

R in REBOH Melting Point Boiling Point Reference
CZHS- ~51 to -h8 35-37/75 mm. 3
CHC1=CH- 66-68/3 mm. b
CgHg- 210-213/1 mm. 2
prl-C6H4- 75 5
prr-C6H4- 113 7
82-8h 2
prHBO-CGH4 107 i 7
prGHg-CGH4 >300 o
2—CH3-5-Cl-CSH3- 81 5
gfclohs- 172 7'
2:010H7- 105-106 8
chs-g-c 10H 1, -* 8

 

*Isolated as the ethanolamine ester melting at 2280C.

EXPERIMENTAL

I. General Procedure

Grignard reagents from bromobenzene, gfbromotoluene, mfbromotoluene,
pfbromotoluene, pfbromoanisole, pfchlorobromobenzene, gfbromonaphthalene,
pfbromobiphenyl, and bromomesitylene were prepared in anhydrous ether
solution. Trimethoxyboroxine, prepared from trimethyl borate and boric
anhydride, was dissolved in anhydrous ether and added to each Grignard
reagent. The reaction mixture was hydrolyzed and the ether layer
removed and distilled yielding an oil containing a mixture of boronic
and borinic acids. The boronic acid was removed by heating this oil

with hot water. The borinic acid was dissolved in ether and converted

to the aminoethyl ester by adding a mixture of ethanolamine in water.

II. Reagents

Bromobenzene - Eastman Kodak Companyu Practical grade. Redis-
tilled and the fraction boiling at 620 and 30 mm. was used.

ngromotoluene - Eastman Organic Chemicals. White label.
Redistilled and the fraction boiling at 650 and 15 mm. was used.

mrBromotoluene - Eastman Kodak Company. White label. Redistilled
and the fraction boiling at 670 and 15 mm. was used.

prromotoluene - Dow Chemical Company. Redistilled and the
fraction boiling at 850 and 30 mm. was used.

prromoanisole - Eastman Kodak Company. White label. Redistilled

and the fraction boiling at 98—990 and 16 mm. was used.

ngromonaphthalene- Eastman Kodak Company. White label. Redis-
tilled and the fraction boiling at 1370 and 15 mm. was used.

prromobiphenyl - Eastman Kodak Company. White label. Used as
received.

Ethanolamine - Eastman Kodak Company. White label. Used as
received.

Diethyl ether - Anhydrous grade dried over sodium metal for three
days.

Trimethyl borate - Anderson Chemical Company. Used as received.

Boric anhydride - Baker Chemical Company. Used as received.

Mesitylene - Matheson-Coleman-Bell. Used as received.

Bromine - Mallinckrodt Chemical Company. Used as received.

prhloroaniline - Eastman Kodak Company. White label. Used as

received.

III. Preparation of Intermediates
A. Preparation of Bromomesitylene

Bromomesitylene was prepared from the method described in Organic
Syntheses (17). In a l-liter three-necked flask equipped with a
stirrer, dropping funnel, and a parallel side arm holding a thermometer
and a reflux condenser were placed 213 g. (1.77 moles) of mesitylene
and 150 m1. of carbon tetrachloride. A rubber tube from the top of
the condenser to the water drain was used to remove the hydrogen bromide
Vapors. The flask was cooled to 1000 in an ice-salt bath. Ninety-six
milliliters (1.87 moles) of bromine in 190 ml. of carbon tetrachloride

'were added over a period of two and one-half hours while the temperature

was maintained between 10-1500. After all the bromine was added, the
mixture was refluxed for one hour. The reaction mixture was washed
with a saturated sodium bisulfite solution, two 200 ml. portions of
water, and two 250 ml. of a 5 percent sodium hydroxide solution. The
reaction mixture was dried over calcium chloride and the carbon tetra-
chloride distilled at atmospheric pressure through a hO cm. Fenske
column. The residue was then added to l-liter of 95 percent ethyl
alcohol which had previously reacted with 17 g. of sodium metal. The
reaction mixture was refluxed for two hours, allowed to stand overnight,
and then diluted with 3-liters of water and separated. The water layer
was washed with three 100 ml. portions of carbon tetrachloride removed
from the first distillation. The extracts were combined with the crude
product and dried over calcium chloride. After the carbon tetrachloride
had been removed by distilling through the Fenske column at reduced
pressure, there was collected 200.6 g. of bromomesitylene at 101-1020

and 15 mm. Yield 58% based on mesitylene.

B. Preparation of Trimethoxyboroxine

The boroxine was prepared following a procedure of Goubeau and
Keller (18). In a 500 ml. one-neck flat4bottomed flask were placed
69.h g.(l mole) of boric anhydride and 103.8 g. (1 mole) of trimethyl
borate along with a glass covered stirring bar. The flask was con-
nected to a reflux condenser and placed in a heating mantle on top of
a magnetic stirrer. The reaction mixture was stirred and refluxed
from two to four hours or until the boric anhydride dissolved. The

flask was cooled to room temperature and then immersed in a dry ice-

lO

isopropyl alcohol bath until the contents of the flask froze. The
flask was removed from the bath, permitted to warm to room temperature,
and the trimethoxyboroxine stored in a glass stoppered Erlenmeyer flask.
At one time during this research it became necessary to prepare
trimethoxyboroxine from boric anhydride obtained from other companies.
Boric anhydride from Matheson-Coleman-Bell and Anderson Chemical Company
were used, but in both cases the boric anhydride would not dissolve
in the trimethyl borate even after prolonged reflux periods of 50 hours.
It was believed that the boric anhydride contained water, so a sample
was heated in a vacuum oven for 2h hours at 200°C and at a pressure of
30 mm. of mercury using phosphoric anhydride as the dehydrating agent.
The boroxine could not be prepared using the boric anhydride derived
in this manner.
Boric anhydride was then prepared by dehydrating boric acid using
a vacuum oven at 20000 and at a pressure of 30 mm. of mercury with
phosphoric anhydride as the dehydrating agent. The sample was heated
for to hours. Trimethoxyboroxine was prepared from the boric anhydride

obtained from the dehydration of boric acid.

C. Preparation of prhlorobromobenzene

prhlorobromobenzene was prepared following the procedure from
Organic Syntheses (19). A mixture of 127.5 g. (1 mole) of pfchloro-
aniline and 300 ml. (2.5 moles) of h8 percent hydrobromic acid were
placed in a 2-liter flask. The flask was cooled to 00 in an ice-salt
bath. A solution of 70 g. (1 mole) of sodium nitrite in 125 ml. of

‘water was added rapidly keeping the temperature below 100 by adding

ll

ice to the solution. While the diazonium solution was being made, a
mixture of 79 g. (0.55 mole) of cuprous bromide and 80 ml. (0.6 mole)
of L8 percent hydrobromic acid were heated to boiling in a 5-1iter
three-necked flask equipped with a steam inlet tube, a dropping funnel,
and a condenser set for distillation and provided with a 2-liter
receiving flask. The diazonium solution was added to the cuprous
bromide-hydrobromic acid solution by way of the dropping funnel while
a current of steam was passed through the mixture. The addition was
over a period of A5 minutes. When the addition was complete, the
mixture was steam distilled until no more oil was recovered. The
distillate was cooled in an ice-water bath. The solid recovered from
the distillate was filtered and recrystallized twice from ethanol-water
mixture. The yield of pfchlorobromobenzene was 137 g., 71.6% based on

p-chloroaniline. Melting point 67°C (lit. m.pt. 67.n°(2o)).

IV. Preparation of Grignard Reagents
A. General Procedure

Grignard reagents from bromobenzene, gfbromotoluene, mfbromotoluene,
pfbromotoluene, pfbromoanisole,[pfchlorobromobenzene, gfbromonaphthalene,
and bromomesitylenaiwere prepared following the procedure from Organic
Syntheses (21). In a l-1iter three-necked flask equipped with a stirrer,
dropping funnel, and a parallel side arm holding a reflux condenser
and a thermometer were placed 9.7 g. (0.h mole) of magnesium turnings.
The condenser and dropping funnel were protected with calcium chloride

~

‘11- .
Flve tenths of a milliliter of ethyl bromide was added as an initiator.

12

drying tubes. Ten milliliters of anhydrous ether and 5 ml. of the
bromide were added to the flask. After the reaction was initiated, the
stirring started, and the remainder of 62.8 g. (0.h mole) of bromo-
benzene, 68.h g. (0.h mole) of gfbromotoluene, 68.h g. (0.h mole) of
gybromotoluene, 68.h g. (0.h mole) of pfbromotoluene, 7h.8 g. (0.h mole)
of pfbromoanisole 76.h g. (0.h mole) of pfchlorobromobenzene 82.8 g.
(0.h mole) of gfbromonaphthalene, or 80.0 g. (0.h mole) of bromomesitylene,
which had previously been diluted with 170 m1. of anhydrous ether, was
added to the flask over a period of one hour. After the addition, the
reaction mixture was refluxed for two hours. The contents of the flask
'was cooled to room temperature, a 5 m1. aliquot was removed for
analysis, and the ether solution of trimethoxyboroxine was added to the
remainder of the Grignard reagent as described in section V.

The 5 m1. aliquot was analyzed following a procedure of Fieser
(22). Twenty milliliters of distilled water was added along with an
excess of standard 0.h531 N hydrochloric acid to the aliquot, and the
excess of acid was neutralized with standard 0.h532 N sodium hydroxide
to a methyl orange end point. The following is a sample calculation
using the Grignard reagent from bromobenzene as the example.

hO.7O m1. of O.h53l N HCl

c.018h

0.0025

0.0089 moles of Grignard in

H

20.09 ml. of 0.h532 N NaOH

aliquot
220 m1. total volume
229- = S x = 0 398 moles of Grignard reagent pre-
X 0.00 9 '

pared.

13

B. Preparation of the Grignard Reagent From prromobiphenyl

In a 1-liter three-necked flask equipped with a stirrer, dropping
funnel, and parallel side arm holding a reflux condenser and thermometer
were placed 9.7 g. (0.h mole) of magnesium turnings. The condenser
and dropping funnel were protected with calcium chloride drying tubes.
One hundred sixty milliliters of anhydrous ether was saturated with
pfbromobiphenyl. Twenty milliliters of the ether solution and 0.5 m1.
of ethyl bromide were added to the flask. After the reaction was
initiated, the remainder of the solid 93.2 g. (0.h mole) of pfbromo-
biphenyl was added through the side arm at a rate fast enough to keep
the ether refluxing. The reaction mixture was not stirred. The remain-
ing 1h0.m1. of the saturated ether solution was added simultaneously
with the solid. Twenty milliliters of ether was used to wash the
dropping funnel and added to the flask. After the addition was com-
plete, the reaction mixture was stirred and refluxed for three hours.
The contents of the flask were cooled to room temperature, a 5 m1.
aliquot was removed for analysis, and the ether solution of trimethoxy-
boroxine was added to the remainder of the Grignard reagents as des-
cribed in section V. The aliquot was analyzed following the procedure

of Fieser (22).

‘V} Reaction of the Aryl Magnesium Bromide With Trimethoxyboroxine
A . General Procedure

The addition of trimethoxyboroxine to the aryl Grignard reagent
fines carried out in exactly the same manner for all the reactions. The

fkillowing is the general procedure and the reaction with phenyl

lb

magnesium bromide will be used as the example.

To a l-liter three—necked flask containing the phenyl magnesium
bromide equipped with a stirrer, dropping funnel, and a parallel side
arm holding a reflux condenser and a thermometer was added 100 m1. of
anhydrous ether. The condenser and drOpping funnel were protected
with calcium chloride drying tubes. The contents of the flask were
cooled to 2500 by placing the flask in a water bath. Analysis showed
that 0.398 mole of phenyl magnesium bromide had been prepared. To this
solution 7.7 g. (0.0hh mole) of trimethoxyboroxine (9 to 1 mole ratio
of Grignard reagent to trimethoxyboroxine) was dissolved in 150 m1. of
anhydrous ether and added dropwise over a period of two hours while
the temperature was maintained between 2h-26OC. The temperature was
kept constant by adding ice to the water bath. After the addition of
the boroxine, the reaction mixture was stirred for three hours at the
same temperature. Forty milliliters of concentrated hydrochloric acid
in 300 ml. of water was used to hydrolyze the reaction mixture. The
ether layer was separated and washed twice with 100 ml. portions of
water. Diphenylborinic acid was isolated from the ether solution by
the procedure given in Part VI and converted to the aminoethyl ester.
The yield of ester from this reaction was 19 g., 62.h%. A summary of

the yields of the other borinates is given in Table II.

28. Effect of Temperature
The effect of temperature on the percent of aminoethyl diphenyl-
knorinate isolated was studied. The procedure was the same as given in

tflle preceding paragraph except that the temperatures of ~600, 6°, 160

TABLE II

YIELD OF AMINOETHYL BORINATES*

15

 

 

 

Compound Grams Grams Percent
Obtained Theoretical Yield
Aminoethyl diphenylborinate 19.0 30.h 62.h
Aminoethyl di(oftolyl)borinate 18.9 31.9 59.3
Aminoethyl di(m-toly1)borinate 18.6 30.8 60.3
Aminoethyl di(pftolyl)borinate 10.0 30.3 33.0
Aminoethyl di(pfanisyl)borinate 13.0 3h.2 38.0
Aminoethyl di(gfnaphthy1)borinate 25.0 h0.3 62.0
Aminoethyl di(p:bipheny1)borinate 11.0 26.h h1.7
Aminoethyl dimesitylborinate 0.0 3h.0 0.0
.Aminoethyl di(p:chlorophenyl)borinate 5.3 37.5 1h.2

*One to 9 mole ratio of boroxine to Grignard reagent at 2h-26OC.

16

and 350 were used. The temperature was controlled at -600 by immersing
the reaction flask in a dry ice-isopropyl alcohol bath with the
temperature range between ~65 to -550C. At 60 the temperature was
controlled by a salt-ice bath with the range between 5-700. At 160

the reaction flask was immersed in a circulating water bath and the
temperature controlled between two degrees, and at 350 the reaction
mixture was heated to the reflux temperature of ether with the
temperature remaining constant over the reaction period. These results

are summarized in part I of the result section.

0. Effect of Ratio Change

The effect of changing the mole ratio of trimethoxyboroxine to
Grignard reagent was also studied. Here the reaction procedure was
identical with that given above except that the mole ratios of tri-
methoxyboroxine to Grignard reagent of 1 to 3, 1 to 6, and l to 12 were

“used. The results are summarized in Part II of the result section.

‘VI. Isolation and Purification of Reaction Products
.A. General Procedure for Borinates

The following isolation and purification method, adapted from a
Ixrocedure of Letsinger (1), was used in all of the reactions. The ether
solution from the reaction of trimethoxyboroxine with the Grignard
J?eagent was heated on a steam bath to remove the solvent. One hundred
nmilliliters of water was added to the resultant oil and the mixture
Enas heated on a steam bath for 15 minutes to remove the boronic acid

lfllat had dissolved in the ether. The oil was separated from the water

17

and diluted to 250 ml. with ether. The water layer was evaporated to
recover the boronic acid. A mixture of ethanolamine in an equal volume

of water was added to the ether solution and stirred until the precipitate,
aminoethyl borinate, ceased to form. The solid was filtered, washed

with three 50 m1. portions of water, and dried. The solid was recrystal-
lized by dissolving in the least amount of hot ethyl alcohol, and water
was added until the first appearance of a solid. The beaker was cooled

in an ice-water bath and filtered through a Buchner funnel. The solid

was washed with two 50 ml. portions of water and dried in a vacuum

desiccator. '

B. Other Methods
A study was made in effort to find a satisfactory procedure for
the isolation and purification of the aminoethyl diphenylborinate. The
best procedure found is given in part A. The following are other
methods tried:
1) Preparation of the ester without removal of the boronic acid.
The ether solution was placed in a one-neck flask equipped with
a stirrer. An equal volume of ethanolamine and water was placed
in the flask, and the contents of the flask stirred for one
hour. The aminoethyl diphenylborinate was filtered, washed
with water, and recrystallized.
2) Removal of the borinic acid by preparation of the potassium
salt followed by esterification. In a two-necked flask equipped
with a stirrer and reflux condenser were placed the ether

solution and an excess of l N potassium hydroxide. The reaction

l8

mixture was stirred and refluxed for three hours. The water
layer was separated and acidified with dilute hydrochloric acid.
The resulting oil was extracted with three 75 ml. portions of
ether and treated with a solution of ethanolamine in water.
The aminoethyl diphenylborinate was filtered, washed with
water, and recrystallized.

3) Direct removal of the boronic acid by treatment with water.
In a two-necked flask equipped with a stirrer and reflux con-
denser were placed the ether solution and 100 ml. of water.
The reaction mixture was refluxed for one hour. After cooling,
the ether layer was separated and treated with ethanolamine in
an equal volume of water. The aminoethyl diphenylborinate was
filtered, washed with water, and recrystallized.

The results obtained from the study of different methods of iso-

lation are summarized in Part III of the result section.

C. Purification of the Boronic Acids

Phenylboronic acid, gftolylboronic acid, mftolylboronic acid,
11~tolylboronic acid, pranisylboronic acid, and pfbiphenylboronic acid
:isolated from the reaction mixture were recrystallized from water.
ggéNaphthylboronic acid and mesitylboronic acid were recrystallized from
a benzene solution. Table III summarized the observed and the literature

melting points for these acids.

TABLE III

MELTING POINTS OF BORONIC ACIDS*

19

 

 

 

 

Compound MeltinggPoint Reference
Obs. Lit.
Phenylboronic acid 2lh-215 216 12
ngolylboronic acid 167-168 168 7
meolylboronic acid 156~l57 157 7
'137-lto 23
prolylboronic acid 238-239 2h0 12
21:5 7
ijAnisylboronic acid 207-208 209-210 7
‘ngaphthylboronic acid 215—216 219 2b
202' 7
laéBiphenylboronic acid 229-231 232~23h 2h
Mesitylboronic acid 170-171 --

 

“Melting points were obtained using a modified Thiele apparatus
with mineral oil as the bath liquid.

20

VII. Analysis of the Products
A. Neutralization Equivalents

Neutralization equivalents of the aminoethyl borinates were de-
termined using a procedure of Stone (25) for the calculation of total
amines. Samples ranging from 0.b-0.9 g. (20 meq.) were weighed into a
250 ml. beaker and 100 m1. of isopropyl alcohol was added. The solu-
tion was titrated with standard 0.2h05 N hydrochloric acid in isopropyl
alcohol to a sharp decrease in apparent pH as measured with a pH meter
using glass and calomel electrodes. A plot of change in apparent pH
per change in volume against volume was used to determine the exact
neutralization equivalent. The results are given in Table IV. The
following is a sample calculation using aminoethyl diphenylborinate

as the example.

Wt. of sample 799.5 mg.
Volume of 0.2h05 N HCl 17.75 ml.
Meq. 3.5h5 meq.
Eq. wt. (obs.) 225.3

Eq. wt. (calc.) 225

B. Melting Points

A modified Thiele apparatus with mineral oil as the bath liquid
Baas used to determine the melting point of the esters. The thermometer
Enas calibrated using a Jenaer Normalglas calibrated thermometer. The

Iwesults are summarized in Table IV.

21

0. Carbon, Nitrogen, and Hydrogen.Analysis

Micro-analysis were by Micro-Tech Laboratories, Skokie, Illinois.

The results are summarized in Table V.

D. Boron Analysis

Boron analysis were obtained following a procedure of Johnson (26).
A sample ranging from 0.2-0.h g. (equivalent to 0.15 g. of boric acid)
was placed in a 25 ml. flask fitted with a parallel side arm holding a
small Allihn condenser and a small dropping funnel. Through the addition
tube 0.5 ml. of a saturated sodium hydroxide solution was added, and
while the apparatus was shaken 10 ml. of 5 percent hydrogen peroxide was
added dropwise from the funnel. On completion of the additions the
solution was warmed gently to decompose the peroxide. One and five
tenths milliliters of saturated sodium hydroxide was then added followed
Toy the 31 w addition of 2-3 ml. of 30 percent hydrOgen peroxide. During
'the addition the flask was warmed and shaken. The mixture was then
Ileated to reflux for one-half hour. The flask was removed and its
contents transferred to a nickel crucible (to x h5 mm). The flask was
‘washed with 5 m1. portions of water until the rinsings were neutral to
Zlitmus. The crucible was heated on a steam bath until the rate of
eavaporation became extremely slow, about three hours. The sample was
<3arefully heated with a micro burner until the material solidified.
Tlle crucible was heated slightly stronger until the effervesence ceased.
Tflle crucible was finally heated to red heat for ten minutes. After
(Hooling, the crucible was placed in a 300 ml. beaker with 75 ml. of

halter. After the salts had dissolved, the crucible was removed and

22

rinsed carefully. The solution was heated to boiling and filtered into
a 500 ml. flask fitted with a reflux condenser. Two drops Of a methyl
red solution were added followed by 3 N hydrochloric acid until an
excess of 3-5 ml. was present. The solution was refluxed for one-half
hour. The flask was cooled and the condenser rinsed thoroughly, the
rinsings added to the flask. The solution was roughly neutralized with
10 percent sodium hydroxide, and the exact neutrality with 0.2080 N
hydrochloric acid and 0.1971 N sodium hydroxide. To the neutral solu~
tion were added three drops of phenolphthalein and 10 g. of mannitol.
The solution was then titrated with 0.1971 N sodium hydroxide to the
first faint pink color by the phenolphthalein. The percent of boron
was then calculated from the amount of alkali consumed between the
Inethyl red and phenolphthalein end points. The results are summarized
in Table V. The following is a sample calculation using aminoethyl

[diphenylborinate as the example.

ll

1 ml. of 0.1971 N NaOH 0.00216 g. of boron

5.12 ml. of 0.1971 N NaOH 0.0101 g. of boron
Wt. of sample 0.210 g.

Percent boron h.80%

23

TABLE IV

MELTING POINTS AND NEUTRALIZATION EQUIVALENTS OF BORINATES*

 

 

 

Name MeltingLPoints Neut. EqJ
Obs. Lit. Obs. Calc.
Aminoethyl diphenylborinate 189 190(1) 225.3 225
Aminoethyl di(g:tolyl)borinate 181-181.§ -- 255 253
Aminoethyl di(mftolyl)borinate 180-181 -- 256 253
Aminoethyl di(pftolyl)borinate 186-187 -- 251 253
Aminoethyl di(pfanisyl)borinate l73-l7h -- 287 285
Aminoethyl di(gfnaphthyl)borinate 202-203 -- 326.5 325
Aminoethyl di(pfbiphenyl)borinate 217-218 -- 381 377
Aminoethyl di(pfchlorophenyl)- 223-22h --
borinate

 

*Melting points were obtained using a modified Thiele apparatus
with mineral oil as the bath liquid. Neutralization equivalents
were obtained from following a procedure of Stone (25).

28

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25

RESULTS

I. Effect of Temperature

Table VI and Graph I summarize the results obtained by varying the
temperature in the preparation of aminoethyl diphenylborinate. These
results indicate that a maximum yield of the borinate is obtained when
the reaction proceeds at 250. The small yield of borinate at ~600 and
60 may be explained by reasoning that the activation energy is too high
to form an appreciable amount of the borinic acid at these temperatures.

The boronic acid was not isolated from these reactions because it
is quite soluble in the aqueous acid used for hydrolysis and also
because it oxidizes readily to phenol in water. Since the water
extract contains magnesium salts and boric acid produced by decomposition
of unreacted boroxine, the problem of isolation becomes exceedingly
difficult. It was observed, however, that at ~600 the yield of boronic

acid isolated is the same as the yield of the borinate.

II. Effect of Ratio of Boroxine to Grignard Reagent

Table VII and Graph II summarizes the results obtained by changing
the mole ratio of trimethoxyboroxine to phenyl magnesium bromide in the
preparation of aminoethyl diphenylborinate at 250. These results
indicate that a maximum in yield is obtained when the mole ratio of
trimethoxyboroxine to phenyl magnesium bromide of l to 9. The low
yield at the mole ratio of l to 3 could be explained by reasoning that

the concentration of Grignard reagent is too low to force the reaction

 

 

26

TABLE VI

TEMPERATURE EFFECT IN THE REACTION OF TRIMQTHOXYBOROXINE
WITH PHENYL MAGNESIUM BROMIDE

 

W 2::_ 7.

Temperature 0C. Percent Yield of
Aminoethyl Diphenylborinate

 

~60 11.2

o 18.t
16 h2.6
25 62.11
35 51.7

 

v

*One to nine mole ratio of trimethoxyboroxine to Grignard
Reagent.

TABLE VII

EFFECT OF CHANGING THE MOLE RATIO OF TRIMETHQXYBOROXINE TO
PHENYL MAGNESIUM BROMIDE AT 25

 

 

 

Ratio of Boroxine Percent Yield of
to Grignard Aminoethyl Diphenylborinate
1-3 1607’ 15
1-6 56.2
1‘9 62oh

1-12 113.7, 115

27

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

   

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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1+..+1+111, , , . . ... . .. . . . .. . .
...H. . . , . .. .,.. ... H. .. .H. . _ - .. ._ .
11-. . . OH
. H H . .m,. . , .d .
,. H. .. . ; .L . . . . . .. . H . ... J “H
. .. .. . H Um H . .. 1 I . . .. . «SW S
H. . .H . “H H H P3... 1. T
9 HH . .H. . 1 W ,. . , , H,.p m .3 ,w
111w. . . .H . . 1. fi1 . . .. 1 .,. ”a 41
1H”... .. ..me H1 1 . .1.” 1 Wu... H.
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11.1%? . ., _ , . . 1 . . , . 1 1 O .. .411.
... . _ . ,. . . .. , .:
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1 . w . , . . . , 2., ..
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.. M. H. L. H - - H11...H.. «. ,. . .. ..H .I1TH. . ..M;H...H
H. .H H 1H : HH uzmmmmm ohmcwflno op mqflxonom Mo Oflpmm . pm .:
.. .% H . A .... ; mac: .m> mpwafluonazflosmfim ahsvmocflsd mo pqmopmm y. g“ th.uu
H .11: H. h 1 ..H. H 1? 5 £3 3.“
1.1..-+..-ilt.f . . . . . ._ - :1:
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:.H ..U , .JH . ..HH H UK ..th ”T“. M.. T”. UH “Sufi, THHHHHH “1.3 HHHHLH... .... . i . ...HH ......n.
TUNNF ...wfiw . . h ...E. .L 1.HH.....H,N..U.H.I1HH “I. .H “HUM“ “H” ”H”? ..HHHH 3“ “RH: ..UH :.. H. . ..Uvflfi
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..... .-...H---1. m .. . .. .. . .. ....” ....-. .,. ”3...”- .....HH..-1 .. . .... . -.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

29

in favor of the borinic acid. This is reasonable because boric acid
was isolated from the reaction mixture after hydrolysis and was not
found in any of the other reactions of this series. Since boric acid
is soluble in aqueous solutions, any boric acid formed from the
hydrolysis of the unreacted boroxine would dissolve in the acid solu-
tion used for hydrolysis. Boric acid was recovered only when it was

present in larger amounts than that required to saturate the solution.

III. Methods of Isolation

Four methods were studied in an attempt to find the most satis-
factory method of isolation of aminoethyl diphenylborinate. These
methods were described in section VI of the Experimental. The results
from this study are summarized in Table VIII. Method 1, removal of
the solvent and boronic acid followed by esterification, which gave
the highest yield of ester (62.h%) was used to isolate the borinic
acids in all subsequent reactions of Grignard reagents with the boroxine.
The yield obtained by method 2 (preparation of the ester without
removal of the boronic acid) is slightly more than one-half that of
method 1, and shows the necessity of removing the boronic acid before
attempting esterification. Method 3, which attempts to remove the
borinic acid from ether by extracting with aqueous potassium hydroxide,
gives surprisingly lOW'yields (h0.7%) 0f the ester. This is difficult
to explain but suggests that extraction with aqueous base is quite
inefficient. Method h, removal of boronic acid from the reaction mix-

ture by boiling with water and subsequent esterification of the remaining

30

TABLE VIII

COMPARISON OF SEVERAL METHODS FOR ISOLATION OF BORINIC ACIDS-x-

 

 

 

Method** Aminoethyl Diphenylborinate
Grams Grams Percent Ester
Obtained Theoretical Obtained
1 11.1 17.7 62.h
2 6.2 17.7 35.0
3 7.2 17.7 h0.7
h 8.3 17.7 h6.9

* O O O I O O
Identical and optimum reaction conditions were used in each case.

“"The four methods studied are:

1. Removal of the solvent and boronic acid followed by
esterification.

2. Preparation of the ester without removal of the boronic
acid.

3. Removal of the borinic acid by preparation of the potassium
salt followed by esterification.

h. Direct removal of the boronic acid by treatment with
water.

31

borinic acid, gave a h6.7% yield of ester. This suggests that the

boronic acid cannot be successfully removed with boiling water.

IV. Effect of Steric Factors

The study of steric effects in this reaction is illustrated in
Table IX. Results of reacting phenyl, gftolyl, gynaphthyl, and
mesityl Grignard reagents with the boroxine gave a clear indication
of the susceptibility of this reaction to steric factors. Substitution
of one gfmethyl group has virtually no effect on the yield of borinate,
whereas blocking both ortho positions of the Grignard completely prevents
the reaction. No reaction between mesityl magnesium bromide and boroxine
was evidenced even after increasing the reaction time to fifteen hours,
five times the usual procedure. It is interesting to note that the
yield of the di(gftolyl)borinic ester is nearly twice that of the
di(pftolyl)borinic ester. Since electrical factors are nearly the same
in these two compounds, the steric effect of the single gfmethyl group
appears opposite to that of the two gfmethyl groups. The yield of
ester from the gfnaphthyl Grignard is almost identical with that

obtained from the g—methyl compound.

V. Effect of Electrical Factors

The influence of electron donating and electron withdrawing sub-
stituents in the Grignard reagent has been studied with phenyl, pftOIyl,
mftolyl, pranisyl, pfchlorophenyl, Erbiphenyl, and gfnaphthyl Grignard
reagents. These results are summarized in Table X. In general, the

results indicate that the highest yields of ester (62% of theoretical)

32

TABLE IX

EFFECT OF STERIC FACTORS*

 

Percent Yield of

 

Compound Borinate
Aminoethyl diphenylborinate 62.h
Aminoethyl di(27tolyl)borinate 59.3
Aminoethyl di(gfnaphthyl)borinate 62.0
Aminoethyl dimesitylborinate 0.0

 

*One to nine mole ratio of boroxine to Grignard reagent at 250-

TABLE X

EFFECT OF ELECTRICAL FACTORS*

 

Compound Percent Yield of
Borinate
Aminoethyl diphenylborinate 62.h
Aminoethyl dng-naphthyl)borinate 62.0
Aminoethyl diQp-biphenyl)borinate hl.7
Aminoethyl diQp-anisyl)borinate 38.0
Aminoethyl diQp-tolyl)borinate 33.0
Aminoethyl di(pfchlor0phenyl)borinate lb.2**
Aminoethyl di(mftolyl)borinate 60.3

*One to nine mole ratio of boroxine to Grignard reagent at 25°.

**Low-yield due in part to air oxidation of the borinic acid.

33

are obtained with the phenyl and Ernaphthyl compounds. The Erbiphenyl
and pranisyl Grignards gave approximately the same yield (h0% of
theoretical), somewhat lower than that obtained from the first two
members of the series. The yield in the case of the pftolyl compound
was 33%, somewhat less than the p-anisyl and p-biphenyl and signifi-
cantly less than the mftolyl which was 60.2%. Finally, the pfchloro-
phenyl Grignard reagent gave a poor yield (lh.2%). The actual yield
-is probably somewhat higher than this, but the di(pychlorophenyl)
borinic acid is especially susceptible to autoxidation. This oxidation
accounts in part for the low yield.

In general, it appears that both electron donating and electron
withdrawing substituents decrease the yield of borinic acid in this

reaction.

3h

DISCUSSION

The study of the effect of temperature, mole ratio of boroxine to
Grignard reagent, steric, and electrical factors were made to gain
insight into the nature of this new reaction, to explore its scope,
and to attempt to elucidate a possible mechanism.

The significance of the effect of temperature suggests that tri-

G

B
O/ \O

l
{ORG/BC}

could be found at low temperatures. This observation is founded on the

phenylboroxine,

following facts. First, the isolated yield of boronic acid is the same
as that of the ester of the borinic acid. If the boronic acid is
present before hydrolysis, it should react with the excess Grignard
reagent. This reaction has been shown to proceed at these conditions
by Letsinger (8). The second reason for the suggested compound is that
the boroxine ring should be stable at this temperature as it is formed
under similar conditions.

At higher temperatures increased yields of borinic acids were
obtained. It is conceivable that the initial reaction is the preparation
of triphenylboroxine. Two facts suggest that this may not be the case.
First, the isolation of boric acid from the reaction mixture. This

can be obtained from the hydrolysis of either trimethoxyboroxine or a

35

mono- or di-substituted phenyl boroxine, but not from triphenylboroxine
which would give only phenylboronic acid. Second, at the higher
temperatures the boroxine ring becomes unstable as shown by its
decomposition at 680.

The increased yield of borinic acid could be explained by the
increase in energy acquired by the Grignard reagent which facilitates
its reaction with the boron compound. The attacking reagent could
do one of two things. The Grignard reagent could cause complex

formation, as Shown in Figure I, or cause the ring to rupture, as shown

in Figure II.

OCR3 OCH3

B B
\

O/ O ’ \O
H CO 1'3 R-R H CO B R/R
3 \O/ \ 3 \ \OCH3

, OCR3 0ng

I

MEX

I II

The significance of changing the ratio of boroxine to Grignard
reagent, in addition to supporting the Law of Mass Action, lies in the
observation that considerable amounts (15%) of borinic ester are formed
.at a 3 to 1 ratio of Grignard reagent to boroxine. Since the yield of
Inorinic acid exceeds that of boronic acid, it appears that the reaction
of the Grignard reagent occurs more readily at the boron atom containing
a phenyl group than at a boron atom containing a methoxy group. This

siggests that a phenyl group on boron activates the boron for further

36

attack. This activation is not noticeable at the lower temperatures.

Further support for this picture comes from the studies at 6 to l
and 9 to 1 ratios of Grignard reagent to trimethoxyboroxine. In these
two cases, even though there is enough Grignard reagent to form the
theoretical amount of borinic acid, boronic acid and boric acid are
isolated after hydrolysis.

One interpretation of this observation is that two Grignard mole-
cules attack a given boron atom before the ring ruptures. In fact two
(or even all three boron atoms) may be doubly substituted by phenyl
groups before ring rupture occurs. Rupture of the ring gives rise to
borate type structures which can react slowly with the Grignard to give
boronates and ultimately borinates. That the entire reaction cannot
proceed by an instantaneous decomposition of the ring to the borate
structure followed by reaction of this structure with Grignard reagent
is shown by the fact that borates react with Grignard reagents under
these conditions to give yields of borinates less than half those
obtained in the present reaction.

The significance of the steric effect is illustrated by the re-
action of mesityl magnesium bromide with the boroxine. Only mesityl-
boronic acid is isolated. This accentuates the importance of blocking
the area around the small boron atom thus preventing attack by a second
substituent. In the case of gftolyl magnesium bromide the yield is
approximately equal to that obtained from the phenyl Grignard and nearly
twice that from the pftolyl compound. The high yield from the gftolyl

compound, clearly opposite to its expected behavior on the basis of

37

both steric and electrical grounds can be explained by reasoning that
the ortho methyl group weakens the carbon-magnesium bond by steric
hindrance. This assists the reaction by making the magnesium more
available for coordination with the oxygen atom of the boroxine.

On the basis of the above reasoning, the following general
mechanism is proposed. This mechanism has not been established but is
included partly as a working guide toward a better understanding of
the reaction and partly to stimulate thinking on future research in
this area.

The initial reaction is probably

OCR3 R
I
B B
\
?/’ \\O 0” O
Rng + I I I + Mg Br(OCH3)
HBCO-B B-OCH3 "’ HBCO-B B-OCR3
R
Followed by: I
If ‘x
R O O
a A to
R” 3
l I + RMgX At low temperature
\0 ’ RxB/R
O, \O"ng
l
O-B B-OCH
HBC ‘0’ 3

At higher temperature

f‘f.“"--"""‘~

38

The complex, I, may decompose by ring rupture or react with more

Grignard reagent. R‘ ’R
O/B
R‘B /R I ngX
O/B \O’ng / H3 CO ~B\ O/B‘OCH3
HacO-é\\OI/R-OCH3 II
RMex.
I
R\B/R
O/ \O,,ng

l
R-B\O/B—OCH3

Compound II reacts slowly to yield boronic and borinic acids.

R IR R\ ’R
\
O/ Ong O/B\O---ng
I I + Rng ———-> R I
R-B\ E—OCH3 \,B\ R-OCH3
O’ R 9’
flex
III

Complex III on hydrolysis gives two molecules of borinic acid and

one of boric acid.

 

39

CONCLUSION

. The reaction between trimethoxyboroxine and aryl Grignard reagents

is found to proceed to give aryl boronic and aryl borinic acids.

. The yields of borinic acids isolated as the aminoethyl ester ranged

from lh—o2 percent.

. A mechanism is proposed which is supported by studies of effect of

temperature, effect of changing ratio of boroxine to Grignard

reagent, and effect of steric and electrical factors.

Aminoethyl esters of di-(gftolyl), di-(pftolyl), di-(mftolyl), and
di-(pfbiphenyl) borinic acids and mesitylboronic acid were prepared
by this reaction. These acids have not previously been reported in

the literature.

Aminoethyl esters of diphenyl, di-(g-naphthyl), di-(p-anisyl), and
di-(p-chlorophenyl) borinic acids and phenyl, gftolyl, mftolyl,
pftolyl, prehisyl, Ernaphthyl, and pfbiphenyl boronic acids were also
prepared by this method. These boronic and borinic acids have been

reported.

. The yields of the borinic esters obtained from this reaction were

in nearly all cases twice that obtained from currently used methods.

l.

2.

10.
ll.
12.

13.

1h.

15.

16.

17.

to

BIBLIOGRAPHY

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A. Michaelis, M. Behrens, J. Robinson, and W} Geisler, Ber., 21;
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§§, t07 (1936).

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1251, b023 C. A., go, 2995d (1952).

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L. L. Quill, P. R. Ogle, Jr., and W} T. Lippincott, Unpublished
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L. I. Smith, Organic Synthesis, Coll. Vol. II, John Wiley and Sons,
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hl

18. J. Goubeau and H. Keller, Z. anorg. Chem., 262, 1 (1951).

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22. L. R. Fieser, Experiments in Organic Chemistry, Second Edition
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23. D. L. Yabroff, G. E. K. Branch, and B. Bittman, J. Am. Chem. Soc.,
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CHEMISTRY LIBRARY

Date Due

 

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OF :SA‘IEI‘IMEI‘NT OF CHEMISTRY

DE EAST LANSING, MICHIGAN

‘ CHEMISTRY LIBRARY
TneSIS c 9 “R”
Povlock, . Q 1

The reactioh of trine thoxy‘ooroxine

with some aryl Grignard reagents.

The 35. a, CHEMISTRY LIBRARY
Povlock, c.2

The reacti
I — on ,
With some aryd trinetno

 

IYboroxine A
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