A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1964, 44, 51
DOI: 10.15227/orgsyn.044.0051
Submitted by P. L. Pickard1 and T. L. Tolbert2.
Checked by C. L. Dickinson, H. D. Hartzler, and B. C. McKusick.
1. Procedure
The apparatus consists of a 1-l. three-necked flask equipped with a mechanical stirrer, a 250-ml. dropping funnel, and a Friedrichs reflux condenser fitted with a calcium chloride drying tube. Magnesium turnings (13.4 g., 0.55 g. atom) and 200 ml. of anhydrous diethyl ether are put in the flask (Note 1). Slow stirring is started, and 4 ml. of bromobenzene (Note 2) is added from the funnel. After reaction has started (Note 3), the stirring rate is increased, and moderate reflux is maintained by addition of 80.5 g. of bromobenzene (making a total of 86 g. or 0.55 mole) in 100 ml. of ether. The solution is refluxed for 30–45 minutes after the addition and is cooled to room temperature. Stirring is continued while a solution of 51.5 g. (0.50 mole) of benzonitrile (Note 2) in 100 ml. of ether is added slowly enough (Note 4) to maintain only a gentle reflux. On completion of the addition, the reaction, mixture of pale-yellow liquid and white solid is refluxed with stirring for 4–6 hours. The stirred mixture is cooled to room temperature, and the Grignard-nitrile complex is decomposed by cautious addition of 120 ml. (3 moles) of anhydrous methanol (Note 5).
On completion of the methanol addition, the mixture is stirred for 30 minutes and filtered. Low-boiling material is stripped from the filtrate, and the residue is distilled through a 45-cm. Vigreux column at reduced pressure. There is a fore-run, b.p. 120–127° (3.5 mm.), that weighs about 5 g. Then 55–73 g. (61–81%) of diphenyl ketimine is collected at 127–128° (3.5 mm.) or 151–152° (8 mm.); n20D 1.6180–1.6191 (Note 6). The product should be stored under nitrogen to prevent yellowing.
2. Notes
1. Freshly opened commercial (Baker and Adamson) anhydrous ether is suitable. The checkers found it more convenient to use commercial phenylmagnesium bromide than to prepare it. They obtained 80 g. (88%) of the ketimine by charging the flask with 175 ml. (0.525 mole) of 3N phenylmagnesium bromide (Arapahoe Chemicals, Boulder, Colorado), then adding 51.5 g. of benzonitrile as described.
2. Both bromobenzene and benzonitrile (white label grade, Eastman Kodak Company) were distilled before use.
3. If the reaction does not start spontaneously, a crystal of iodine may be added and the mixture may be warmed.
4. Care should be taken to prevent a buildup of unreacted nitrile that could result in uncontrolled reaction.
5. The methanol should be added as fast as possible. A quantity of gummy material will form as the decomposition progresses, but with continued addition of methanol it will be rapidly converted to crystalline methoxymagnesium bromide.
6. Gas chromatographic analysis of the product from three consecutive preparations showed less than 0.1% impurity. Similar results were obtained on 0.005-ml. samples in an F. and M. 202 Temperature Programed Gas Chromatograph using two columns: a 12-foot column of 10% HiVac grease and 5% Marlex-50 on 100–140 mesh Gas Chrom A, at a constant temperature of 275°, with a helium flow rate of 120 ml. per minute; and a 20-foot column of 20% GE-SE 30 on 100–140 mesh Gas Chrom A, programed at 3.3° per minute from 250° to 300°, with a helium flow rate of 120 ml. per minute.
3. Discussion
This procedure is a modification of the method employed by Moureu and Mignonac,3 who first reported the preparation of ketimines via Grignard-nitrile complexes. The use of methanol in the decomposition step results in higher yields and extends the method to the less stable ketimines.4 The preparation of diphenyl ketimine by the thermal decomposition of benzophenone oxime has been described in Organic Syntheses.5
4. Merits of the Preparation
The procedure is general and is often the best way to make ketimines.

References and Notes
  1. Celanese Chemical Company, Clarkwood, Texas.
  2. Chemstrand Research Center, Inc., Durham, North Carolina.
  3. C. Moureu and G. Mignonac, Compt. Rend., 156, 1801 (1913).
  4. P. L. Pickard and T. L. Tolbert, J. Org. Chem., 26, 4886 (1961).
  5. A. Lachman, Org. Syntheses, Coll. Vol. 2, 234 (1943).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

methanol (67-56-1)

diethyl ether (60-29-7)

benzonitrile (100-47-0)

magnesium turnings (7439-95-4)

nitrogen (7727-37-9)

iodine (7553-56-2)

bromobenzene (108-86-1)

Phenylmagnesium bromide (100-58-3)

Benzophenone oxime (574-66-3)

Diphenyl ketimine (1013-88-3)

helium (7440-59-7)

methoxymagnesium bromide