DE1902412A1 - Process for the preparation of N-mono-substituted 2-aminobenzphenones - Google Patents

Description

Process for the preparation of N-monosubstituted 2-aminobenzophenones

N-monosubstituted 2-aminobenzophenones have as starting products for the preparation of benzodiazepine derivatives substituted in the 1-position has become of great importance. Because a direct Alkylation of the 2-aminobenzophenone leads to mixtures of the mono- and disubstituted compound (J. Org. Chem. 27 (1962) 3785), must be used in the manufacture of the monosubstituted 2-aminobenzophenones Detours are taken.

According to Sternbach and coworkers (J. Org. Chem. 27 (1962) 3781), the tosyl compound of 2-aminobenzophenone is first prepared here, alkylates them with alkylating agents and then splits off the tosyl group again. According to a different procedure one starts with appropriately substituted quinazolines which are alkylated on the nitrogen atom in the 1-position and subsequently saponified (see U.S. Patent 3,322,764).

It has now been found that N-monosubstituted aminobenzophenones easily and in good yield by reacting 3-phenylanthranil ^ n with alkylating agents and subsequent reduction of the resulting quaternary compounds with ring opening ^ can be created.

009832/1955

Ref. 2856

RX

+ HX

R = alkyl

Dialkyl sulfates are primarily used as alkylating agents for this purpose, ' Trialkyloxonium salts and alkyl fluorosulfonates in question, where the 3-phenylanthraniles used as starting materials preferably in the 5-position with chlorine, bromine and trifluorine thyl can be substituted. The reduction of the quaternary salts can be carried out catalytically with the help of the usual catalysts, like Raney nickel, palladium, platinum etc., as well as with nascent Hydrogen, i.e. with iron-acetic acid, zinc-hydrochloric acid, etc.

The alkylation with the aid of the trialkyloxonium salts already takes place at room temperature, while for the alkylation with Dialkyl sulfate temperatures between 70-120 ° are necessary.

The catalytic reduction of the anthranilium salts can take place at room temperature; for the reduction with nascent Hydrogen temperatures between 50-100 ° have proven to be particularly useful.

Q09832 / 1955

- 3 - Ref. 2856

Example I t

355 g (1 mol) of N-methyl-S-phenyl-S-chloro-anthranilium methyl sulfate are suspended in 100 ml of dioxane, 3 g of palladium carbon (5% Pd) are added and the hydrogen pressure is 30-50 atm. hydrogenated until 1 mol of hydrogen is absorbed, the temperature not exceeding 50 °.

After filtering off the catalyst, it is evaporated in vacuo, the residue triturated with water, neutralized by adding alkali, filtered off with suction and recrystallized from alcohol.

Yield: 198 g (81% of theory) of 2-N-methylamino-5-chloro-benzophenone. Mp .: 94-95 °.

The same product is obtained in 60% yield if one 177.5 g of N-methyl-S-phenyl-S-chloro-anthranilium methyl sulfate in 1000 ml of glacial acetic acid are mixed with 215 g of iron powder and 50 ml of water over the course of one hour at 100 ° and this is done for 2 hours Stirring temperature. After cooling, the reaction mixture is filtered off with suction, the 2-N-methylamino-5-chlorobenzophenone formed is obtained both in the residue and in the acetic acid filtrate. The isolation takes place here by boiling the Residue with alcohol and concentration of the alcoholic extract and, on the other hand, by diluting the acetic acid filtrate with Water and filtering off the precipitate.

009832/1955

- 4 - Ref. 2856

Production of the N-methyl-3-phenyl- ■ required as a starting product 5-chloro-anthranilium methyl sulfate:

229.5 g (1 mole) of 3-phenyl-5-chloranthranil and 400 ml of chlorobenzene are heated to 100 and 504 g (4 mol) of dimethyl sulfate are added dropwise over the course of 45 minutes. It will be 1/2 hour at 100 Stirred, cooled, the precipitated crystal sludge filtered off with suction and washed with benzene.

Yield: 320 g (90% of theory).

Example 2 ;

34.5 g (0.1 mol) of N-ethyl-S-phenyl-S-chloro-anthranilium tetrafluoroborate are suspended in 200 ml of dioxane, mixed with 0.5 g of palladium-carbon and at a hydrogen pressure of 30-50 atm. until hydrogenated to take up 0.1 mol of hydrogen. Work-up is carried out as described in Example 1.

Yield: 25 g (85% of theory) of 2-N-ethylamino-5-chlorobenzophenone. Mp .: 56 °.

Production of the N-ethyl-3-phenyl-5-chloro-anthranilium-tetrafluoroborate used as the starting product:

23 g (0.1 mol) of 3-phenyl-5-chloranthranil are dissolved in 100 ml of ethylene chloride and at room temperature with 19 g. (0.1 mol) Triethyloxonium fluoroborate, dissolved in 70 ml of ethylene chloride,

00 * 832/1965

- 5 - Ref. 2856

offset. The quaternary salt precipitates after just a few minutes. The reaction mixture is stirred for a further 2 hours Sucked off the reaction product and washed with ethylene chloride.

Yield: 32 g (94% of theory)
Pp .: 180-182 °.

009832/1955

Claims (1)

- 6 - ·. Ref. 2856 claim Process for the preparation of N-monoalkylated 2-aminobenzophenones, characterized in that 3-phenylanthraniles reacts with alkylating agents and the quaternary salts formed in the process with ring opening to give the N-monoalkylated 2-aminobenzophenones reduced. 00 9 8.3 2/195 5