Method of obtaining 4-phenyl-benzophenone

The present invention relates to a process for the preparation of 4-phenylbenzophenone. This compound may find use as an intermediate in the synthesis of drugs, for example in the synthesis of bifonazole, an antifungal drug.

Methods for obtaining 4-phenylbenzophenone known so far from the literature consist in heating substrates without the use of a catalyst or with the use of a catalyst.

It is known (Nenitzescu, Isacescu, Jonescu, Ann. 1931, 491, 217) to obtain 4-phenylbenzophenone without the use of a catalyst by heating three times excess biphenyl with benzoyl chloride, distilling off excess biphenyl with steam and crystallization of 4-phenyl benzophenone .

The disadvantage of this method is the long heating time of the substrates and the tedious distillation with steam of the reacted biphenyl.

It is also known (LM Lang. HR Henze J. Am. Chem. Soc. 1941, 63, 1939) a method of obtaining 4-phenylbenzophenone, which consists in quickly adding equimolar amounts of benzoyl chloride and biphenyl chloride dissolved in carbon disulphide to a suspension of chloride aluminum in carbon disulphide. The mixture is boiled for four hours, after which the carbon disulphide is distilled off and the product obtained is crystallized. 4-Phenyl-benzophenone is obtained in a yield of about 75%.

The disadvantage of this method is the use of highly toxic and explosive carbon disulphide.

Surprisingly, it turned out that it is possible to condense biphenyl with benzoyl chloride in the presence of aluminum chloride in chloroform, which usually cannot be used in Friedel-Crafts reaction because it reacts with substrates.

The process of the invention consists in preparing a chloroform-stable complex of aluminum chloride with benzoyl chloride. To this end, benzoyl chloride is added dropwise to the suspension of aluminum chloride in chloroform at room temperature. The chloroform biphenyl solution is then added dropwise to the chloroform solution of the aluminum chloride and benzoyl chloride heated to boiling, and the whole is heated.

The advantage of the method according to the invention is the elimination of very toxic carbon disulphide by the use of much less toxic chloroform, and thus the reduction of fire and explosion hazard.

The subject of the invention is further explained in the production example.

Example. In a round-bottomed flask with a capacity of 2 dm³ equipped with a reflux condenser, thermometer, stirrer and dropping funnel placed 80 g (0.6 mol) anhydrous aluminum chloride and 600 cm³ dry chloroform. 69 cm are added dropwise to the mixture³ (0.6 mol) benzoyl chloride and the mixture is stirred at room temperature for 1 hour and then heated to reflux. 61.6 g (0.4 mol) of biphenyl in 200 cm are poured into the boiling solution^J dry chloroform and the whole is refluxed for 1 hour. A mixture of

170 The reaction 632 is poured to 1.0 dm and stirred, then the layers are separated. The chloroform layer after washing is concentrated and the residue crystallized from acetone to give 76.0 g of 4-phenylbenzophenone (74%), m.p. 97-98 °.

170 632

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