Organic Syntheses, CV 4, 392
[I. METHOD A]
Submitted by R. B. Davis and J. A. Ward, Jr.
1.
Checked by B. C. McKusick and R. L. Morgan.
1. Procedure
Caution! These operations should be conducted in a good hood.
A
1-l. three-necked flask is fitted with a
stirrer, a condenser, a
dropping funnel, and a heating mantle.
Sixty-one grams (1.25 moles) of sodium cyanide and 100 ml. of distilled water are added, and the mixture is warmed with stirring for about 15 minutes while the
sodium cyanide dissolves. Then
400 ml. of methanol (Note
1) is introduced, and the mixture is rapidly heated to gentle reflux.
Fifty grams (0.42 mole) of benzyl cyanide is added all at once, followed by dropwise addition of a solution of
53 g. (0.50 mole) of benzaldehyde and
30 g. (0.26 mole) of benzyl cyanide (Note
2). The addition requires about 40 minutes, during which time the reaction mixture turns from yellow to green and crystalline
2,3-diphenylsuccinonitrile begins to separate (Note
3). The reaction mixture is stirred at gentle reflux for 30 minutes after the addition is complete. The reaction mixture, now blue in color, becomes brown as it is cooled to room temperature.
The nitrile is separated from the cooled reaction mixture by suction filtration, washed successively with
150-ml. portions of 75% aqueous methanol, water,
75% aqueous methanol, and
ether, and dried in air overnight. It is obtained as a colorless solid that weighs
84–89 g. (
72–77%) and melts over a range of 1–2° between
202° and 206° (Note
4). It is the
meso-isomer of
2,3-diphenylsuccinonitrile mixed with a small amount of the
dl-isomer. Recrystallization from
glacial acetic acid (about 27 ml. per g.), followed by washing with 150-ml. portions of water,
75% aqueous methanol, and
ether, yields
79–84 g. (
68–72%) of the pure
meso-isomer, m.p.
238–239° (Note
5).
2. Notes
1.
Reagent grade methanol, very low in acetone content, is used; that available from Rascher and Betzold or Baker is satisfactory.
3. Initial precipitation, occurring during the course of the addition, is exothermic. Hence gentle reflux is advised, and the operator should be prepared to remove the heating mantle for a few minutes should the refluxing become vigorous. Early seeding, if seed is available, is helpful in this regard.
4. Prepared mixtures of the isomeric nitriles have been reported to melt over a range of 1–2° between
206° and 221°.2
5. The checkers used a calibrated
thermometer and observed a melting point of
229–230° for an analytically pure sample which was heated in an
open capillary in an oil bath.
[II. METHOD B]
Submitted by J. A. McRae and R. A. B. Bannard
3.
Checked by R. T. Arnold and Stuart W. Fenton.
1. Procedure
Caution! This preparation should be conducted in a good hood.
Two hundred and five grams (1 mole) of α-phenylcinnamonitrile,
4 2250 ml. of methanol, and
750 ml. of ether are placed in a
5-l. round-bottomed flask fitted with a
two-necked adapter supporting a
1-l. separatory funnel and
reflux condenser. The
α-phenylcinnamonitrile is dissolved by gentle heating, and the solution is heated under reflux. A solution of
274 g. (4 moles) of 95% potassium cyanide in 600 ml. of water (which has been preheated to 45°) is added rapidly from the separatory funnel (Note
1). A small amount of
potassium cyanide precipitates. The solution is heated under reflux for 1 hour, after which a solution of
154 g. (2 moles) of ammonium acetate in 250 ml. of water is added rapidly from the separatory funnel (Note
2). Heating is discontinued, and the mixture is allowed to stand for 24 hours. The slightly orange-yellow crystalline product is collected on a
Büchner funnel and washed, first with two 300-ml. portions of water at 60° to remove inorganic salts, then with
800 ml. of 70% methanol for removal of water and some unreacted
α-phenylcinnamonitrile, and finally with two
300-ml. portions of ether for further drying. The colorless needles thus obtained consist of a mixture of the stereoisomeric α,α'-diphenylsuccinonitriles and, after drying at room temperature for 6 hours, weigh
213–218 g. (
92–94%). This mixture of stereoisomers melts over a 1–2° range in the region of
202–206° (Note
3).
The mixed dinitrile can be recrystallized from
glacial acetic acid (using 27 ml. per g.) to give pure
meso-α,α'-diphenylsuccinonitrile. Residual
acetic acid is removed readily by washing the crystalline product with small portions of water, aqueous
methanol (70%), and
ether; yield
95–98% (based on mixed dinitrile); m.p.
240–241.5° (cor.).
2. Notes
1. Care must be exercised to avoid superheating of the solution before addition of the cyanide; otherwise
ether and
α-phenylcinnamonitrile will be lost through the condenser. Superheating can be avoided by adding a boiling chip periodically as the solution approaches its boiling point. No difficulty with superheating occurs after the cyanide has been added.
2. Addition of the
ammonium acetate solution may be omitted; the yield is then
203–208 g. (
87.5–89.6%).
3. The mixture of dinitriles has been reported to melt over a 1–2° range in the region of
206–221°.2 Analysis of a sample of the mixture of dinitriles produced by the present method showed that no impurities are present.
3. Discussion
In addition, 2,3-diphenylsuccinonitriles have been prepared by treating
α-bromo- or α-chlorobenzyl cyanide with
sodium iodide in
acetone solution,
11 and by the condensation of
benzyl cyanide,
benzaldehyde, and
sodium cyanide.
12 The mixture of stereoisomeric 2,3-diphenylsuccinonitriles has been separated into the
meso compound and the racemic form.
13
Method I is more practical than Method II, which had been developed earlier, since it affords
2,3-diphenylsuccinonitrile in a single procedure and in good yields from readily available materials.
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