Checked by R. S. Schreiber and Wm. Bradley Reid, Jr..
1. Procedure
In a
1-l. three-necked round-bottomed flask (Note
1) are placed
90.0 g. (0.456 mole) of benzanilide2 (Note
2) previously dried in an
oven at 120° (Note
3) and
95 g. (0.456 mole) (Note 4) of phosphorus pentachloride. The solids are mixed by shaking, and lumps are reduced by manipulation with a rod. A
short reflux condenser and a
small dropping funnel are attached.
The mixture is heated in an
electric mantle or oil bath at 110° for 30 minutes and heated under reflux at 160° for 90 minutes or until active evolution of
hydrogen chloride ceases (Note
5). To the mixture are added slowly through a dropping funnel first
36.4 g. (0.46 mole) of pyridine (Note
6) previously dried over pellet-form
potassium hydroxide, and then
42.4 g. (0.456 mole) of freshly distilled aniline. The contents of the flask are mixed by swirling. The mixture is heated at 160° for about 20 minutes or until the red color is discharged, at which point the flask is removed from the source of heat. The mixture is cooled to about 90°, and 250 ml. of water is added slowly through the dropping funnel with agitation to ensure separation of the solid product in granular form. After the mixture has cooled to room temperature, the solid is collected on a
Büchner funnel and air-dried.
The crude
diphenylbenzamidine hydrochloride is transferred to a
1-l. beaker and treated with
500 ml. of 28% ammonia water (
hood). The mixture is stirred mechanically and warmed very gently for an hour. The
diphenylbenzamidine is collected on a Büchner funnel and air-dried. The melting point of the product at this stage is
130–136°.
To purify the product it is recrystallized from
80% ethanol (Note 7), using 8–10 ml. per gram of diphenylbenzamidine. The small insoluble residue of unconverted hydrochloride which may remain (Note
8) is removed by filtering the hot solution. The solution is chilled in an
ice-salt bath, and the crystalline product is collected on a Büchner funnel, pressed dry, and finally dried in the air or in an oven at 100°. The yield is
91–100 g. (
73–80%) (Note
9) of product having a melting point of
142–144° (Note
10) and (Note
11). Recrystallization of 100 g. of this material from
800 ml. of 80% ethanol gives
87 g. (
87% recovery) of pure
N,N'-diphenylbenzamidine, m.p.
144–145°.
2. Notes
1. An all-glass apparatus is desirable as cork connections are attacked during formation of the imido chloride. The checkers used mechanical stirring.
2. The
benzanilide should be of good quality, or tarry material will form and interfere with purification of the product.
Benzanilide is readily made by the Schotten-Baumann procedure from
aniline,
10% aqueous sodium hydroxide, and
benzoyl chloride in the proportions 6:30:5, and after crystallization from
95% ethanol is sufficiently pure.
3. The use of
benzanilide dried by fusion
3 did not improve the yield.
5. Isolation of the imido chloride by distillation under reduced pressure offers no advantage.
6.
Pyridine serves to make all the
aniline available. It does not prevent combination of
hydrogen chloride with the
N,N'-diphenylbenzamidine even when two equivalents of
pyridine are used. In the presence of
pyridine the reaction mixture is a suspension and is easily handled. In the absence of
pyridine it solidifies to a cake, which must be pulverized to permit liberation of the amidine from the hydrochloride.
7. A series of tests showed
ethanol of 78–82% by weight (sp. gr. 0.8344–0.8442 at 25.5°; 84–87% by volume) to be the best solvent. To dissolve
1.0 g. of N,N'-diphenylbenzamidine at the boiling point required
15.5 ml. of 94% (by weight) ethanol,
7.24 ml. of 80% ethanol, and
11 ml. of 71% ethanol, and the recoveries on chilling were respectively
45%,
73%, and
45%; ten intermediate concentrations of
ethanol gave results consistent with these. The solubility of
N,N'-diphenylbenzamidine in
methanol is greater than in
ethanol, but recovery is relatively low.
8. The undissolved residue is unchanged hydrochloride and is usually small. If considerable it may be re-treated with
ammonia and the free base recovered.
9. By chilling to 20° the yield is about
68% of pure material that melts at
144–145°. A second crop of less pure material can be obtained from the mother liquor by concentrating and chilling. By chilling in a
Dry Ice-ethanol bath the yield is about
80% but the product is less pure. Admixed tarry material may be removed in large part by extraction with cold
ether, in which the tar dissolves readily.
10. The checkers used a
Fisher-Johns block.
11. This method is capable of extension to the preparation of other N,N'-disubstituted amidines.
5 In some preparations it may be advantageous to remove
phosphorus oxychloride by distillation under reduced pressure before addition of the amine. The method is not wholly satisfactory for preparation of N,N'-diarylformamidines, which are better made by the orthoformic ester method
6 During preparation of
diphenylacetamidine considerable gluey material formed by decomposition of the intermediate
N-phenylacetimidochloride7 is an impediment to the isolation of the product.
8 This amidine is better prepared by the method of Sen and Ray.
9
3. Discussion
N,N'-Diphenylbenzamidine and closely related amidines have been made by several procedures which involve interaction of amines with N-substituted imido chlorides either preformed
10 or formed
in situ from an acylamine by action of
phosphorus trichloride,
11 phosphorus oxychloride,
4 or
phosphorus pentachloride.
5 Diphenylbenzamidine is formed from
aniline and
benzanilidochloroiodide,
12 from
aniline and
phenyl benzimido ether,
13 and from
aniline hydrochloride and
N-phenylbenzamidine.
14 It is obtained also from
carbanilide and
benzoyl chloride,
15 from
carbodiphenylimide and
phenylmagnesium bromide,
16 from
aniline hydrochloride and
benzonitrile at 220–240°,
17 and from
benzanilide and
phenyl isocyanate.
18 Amidines, including
diphenylbenzamidine, are obtainable from nitriles by heating with ammonium or amine salts of sulfonic acids,
19 by heating
benzotrichloride with amines,
20 and from Schiff bases by action of
tert-amyl hypochlorite.
21 Good yields are claimed for a patented process using an acylamine,
benzenesulfonyl chloride, and amine in the presence of
pyridine.
22 The method described is based on the procedures of Wallach
3 and Hill and Cox.
5
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