Organic Syntheses, Coll. Vol. 4, p.68 (1963); Vol. 39, p.3 (1959).
Caution! Benzeneboronic acid
and its anhydride are toxic substances and may irritate mucous tissues such as those of the eyes. In case of contact, carefully wash exposed parts of the body with soap and water (Note 1)
The apparatus consists of a four-necked 5-l. round-bottomed Morton flask2
fitted with a 500-ml. graduated dropping funnel with a pressure-equalizing side arm
, a 1-l. graduated dropping funnel
of the same type, a thermometer
, an efficient mechanical stirrer (Note 2)
, and an inlet for dry nitrogen
. The apparatus is thoroughly swept with dry nitrogen
, and the reaction flask is charged with 1.5 l. of anhydrous ether
, dry nitrogen (Note 3)
being used for pressure transfer.
Three hundred thirty-six milliliters (312 g., 3 moles) of methyl borate
is distilled directly into the 500-ml. dropping funnel shortly before starting the reaction (Note 4)
. One liter (544 g., 3 moles) of a 3M ethereal solution of phenylmagnesium bromide
is pressure-transferred with dry nitrogen
to the 1-l. dropping funnel (Note 5)
. During subsequent operations until the hydrolysis step, a positive pressure of 10–20 mm. of nitrogen
is maintained in the closed system by means of a mercury bubbler
to prevent access of atmospheric moisture. The ether
is cooled to below −60° by a bath of Dry Ice and acetone
and is kept below −60° all during the reaction (Note 6)
. The reactants are added to the well-stirred reaction mixture alternately in small portions, first 10 ml. of methyl borate
and then 30 ml. of phenylmagnesium bromide
, the rate of addition being as rapid as is possible without the temperature of the mixture rising above −60° (Note 7)
. Stirring is continued for an additional 20 minutes below −60° after the addition of the reagents is completed.
The stirred mixture, maintained at or below 0°, is hydrolyzed by the addition of 200 ml. of distilled water during 5 minutes. It is then neutralized by addition of a solution of 84 ml. of concentrated sulfuric acid
in 1.7 l. of distilled water during 15 minutes. The mixture is transferred to a 5-l. separatory funnel
, the ether
layer is separated, and the aqueous layer is extracted with three 250-ml. portions of ether
The combined ether
layer and extracts are transferred to a 5-l. round-bottomed flask equipped with a Hershberg stirrer
a dropping funnel, a Claisen head with a water-cooled condenser
, an electric heating mantle
, and an ice-cooled receiver (Note 8)
. After approximately one-half of the ether
has been removed by distillation from the stirred mixture, 1.5 l. of distilled water is added slowly while the distillation is continued until a head temperature of 100° is reached (Note 9)
While stirring is continued, the aqueous distilland is cooled in an ice bath (Note 10)
. The benzeneboronic acid
, which separates as small white crystals, is collected on a Büchner funnel
and washed with petroleum ether
. The petroleum ether
removes traces of dibenzeneborinic acid
, which are seen in the hot mother liquor as globules of brown oil and which may color the product. The acid is dehydrated to benzeneboronic anhydride
by heating it in an oven
at 110° and atmospheric pressure for 6 hours (Note 11)
. Benzeneboronic anhydride
is obtained as a colorless solid, weight 240–247 g.
) (Note 12)
, m.p. 214–216°.
The submitters found that for a preparation of this size a 1-inch Duplex Dispersator (Premier Mill Corp., Geneva, New York) operating at 7500 r.p.m. provided excellent agitation of the heterogeneous reaction mixture. For smaller preparations (1-l. flask) they found that a Stir-O-Vac (Labline, Inc., 217 N. Desplainer St., Chicago 6, Illinois) operating at 5000 r.p.m. was satisfactory. The type of agitation is very important for, whereas the submitters obtained yields of around 91%, the checkers obtained yields of only 77–80% with either a Morton stirrer2
(excessive splashing deposited some of the reaction mixture on the warm upper walls of the flask) or a Polytron dispersion mill type of stirrer
(there was too much hold-up in the stirrer housing).
) forms a 1:1 azeotrope (b.p. 54.6°) with methanol
Since the presence of even a small amount of methanol
reduces the yield considerably more than would be expected from the stoichiometry, 46,7 methyl borate
stocks should be freshly distilled through a good column to remove as fore-run any methyl borate-methanol
azeotrope which may have been formed by hydrolysis during storage.
Mallinckrodt analytical reagent grade ether
, dried over sodium
, was used. The methyl borate was the commercial product of American Potash and Chemical Corporation
containing 99% ester as received. The phenylmagnesium bromide was purchased as a 3.0M solution in ether from Arapahoe Special Products, Inc., Boulder, Colorado
The yield of benzeneboronic anhydride
is highly dependent upon the reaction temperature, as the following data of the submitters show. At a reaction temperature of 15° the yield was 49%
; at 0°, 76%
; −15°, 86%
; −30°, 92%
; −45°, 92%
; −60°, 99%.
The yields are based on the combined first and second crops of benzeneboronic acid
At a given temperature, the maximum yield of benzeneboronic acid
and the minimum amount of by-product dibenzeneborinic acid
are obtained when neither reagent is present in excess. The addition of small increments of reactants is a convenient approximation imposed by the difficulty of adjusting stopcocks to small rates of flow. Alternatively, the Hershberg dropping funnel8
or other metering device may be used to maintain the stoichiometry. Addition times, which depend upon the efficiency of stirring and heat transfer, vary from about 1 hour at −60° to 15 minutes at 0°.
Stirring is helpful during the ether
distillation to prevent superheating.
Small amounts of benzene
, and biphenyl
, which may be formed in the reaction, are removed by the steam distillation. Enough water has been added to ensure solution of all of the product.
The product crystallizes at 43° with a temperature rise to 45°. The solubility of benzeneboronic acid
in water (g./100 g. of water) is approximately 1.1 at 0° and 2.5 at 25°; the solubility-temperature relationship is linear to at least 45°.
If benzeneboronic acid
rather than its anhydride is desired, it can be obtained by air-drying the moist acid in a slow stream of air nearly saturated with water. The yield of acid is 282–332 g.
One can readily convert the anhydride to the acid by recrystallizing it from water. Benzeneboronic acid
gradually dehydrates to the anhydride if left open to the atmosphere at room temperature and 30–40% relative humidity. The melting point observed is that of the anhydride because the acid dehydrates before it melts.
The submitters report a yield of 91%
and state that an additional 27 g.
) of acid can be obtained from the aqueous mother liquor.
The present procedure is also applicable to the synthesis of substituted benzeneboronic acids.4 Benzeneboronic acid
and its anhydride are of use as starting materials for the synthesis of phenylboron dichloride15
and of various substituted boronic and borinic acids and esters.7,16
This preparation is referenced from:
Copyright © 1921-, Organic Syntheses, Inc. All Rights Reserved