Process for the preparation of ketone compounds

Details Process for the preparation of ketone compounds Process for the preparation of ketone compounds

1991-12-11

1993-08-10

Reamer, James H.

Organic compounds -- part of the class 532-570 series

Organic compounds

Oxygen containing

C07C 4545

Patent

active

052351092

DESCRIPTION:

BRIEF SUMMARY
CROSS REFERENCE TO RELATED APPLICATION

This application is a national phase of PCT/HU90/00026 filed Apr. 18, 1990.


FIELD OF THE INVENTION

The invention relates to an improved, large scale process for the preparation of ketones of formula (I) ##STR2## wherein R is halogen atom or hydroxyl,


BACKGROUND OF THE INVENTION

It is known that the ketones of formula (I) can be used as intermediates for the preparation of isoflavone derivatives (see e.g. HU PS No. 163,515) as well as anabolics since they effect metabolism.
From an industrial point of view those processes are the most advantageous wherein resorcinol is used as starting material, e.g. the desired product may be obtained according to the Houben-Hoesch reaction: wherein the resorcinol is reacted in anhydrous medium with benzyl cyanide in the presence of dry hydrogen chloride gas and anhydrous tin chloride (see e.g. J. Chem. Soc. /1923/, 404 and J. Am. Chem. Soc. 48, 1926, 791). The yield in this reaction is 50% and the drawback of this process is that the hydrolysis of the "ketimine" derivate intermediate is a very corrosive procedure.
Alternatively 2-hydroxy-4-n-butoxy-phenyl-benzyl ketone or 4-hydroxy-2-n-butoxy-phenyl-benzyl ketone may be obtained when reacting the mono-n-butyl ether of resorcinol with phenyl-acetyl-chloride in the presence of pyridine, then removing pyridine by distillation, dissolving the residue in ether, extracting the solution with hydrogen chloride several times, removing the ether by distillation, thereafter treating the 1-phenyl-acetyloxy-4-n-butyloxy-phenol thus obtained in nitrobenzene with aluminum chloride and steam distilling the mixture thus obtained (see Example 7 of HU PS No. 168,744). The starting material of the first step, i.e. the mono-n-butyl ether of resorcinol, can be obtained e.g. when reacting resorcinol with n-butyl bromide in the presence of dimethyl formamide. Regarding that from resorcinol diether derivatives may also be formed, in order to obtain an end product of good quality, the monoethers have to be purified before the second reaction step.
The analogous phenol compound can be prepared by the known, so called Bouveault reaction too, wherein 2 moles of anhyrous aluminium chloride are reacted with phenol. In the first step of this reaction phenoxy-aluminium dichloride forms while hydrogen chloride gas is released. In the second reaction step said phenoxy-aluminium dichloride is then reacted with the acid chloride derivative in the presence of a further mole of aluminium chloride (Olah, Gy:Friedel Crafts and related reactions, Vol. I, page 97, 1963).
The drawbacks of these known processes are as follows:


DESCRIPTION OF THE INVENTION

The present invention relates to a process for the preparation of ketones of formula (I) and salts thereof ##STR3## wherein R, R.sup.2, R.sup.3, R.sup.4, R.sup.6 are the same as mentioned above wherein phenols of formula (II) ##STR4## are reacted with acid chlorides of the formula (IV) ##STR5## in the presence of inert, anhydrous organic solvent and anhydrous aluminum chloride by a method known per se, the mixture thus obtained is decomposed with an aqueous acid solution and the phases obtained are separated. According to the invention the phenol derivative is reacted with 1 mole aluminum chloride--calculated for the phenol derivative--at a temperature between 0.degree. C. and 40.degree. C. in the presence of halogenated hydrocarbon, preferably dichloroethane. Thereafter the complex of the formula (III) thus obtained ##STR6## is reacted with an acid chloride of the formula (IV) ##STR7## preferably in the presence of the solvent used previously at a temperature ranging from 10.degree. C. to 60.degree. C., thereafter adding an aqueous acid solution to the mixture thus obtained, separating the phases and recovering the desired ketone compound from the organic layer.
We have surprisingly discovered that when reacting e.g. resorcinol with 1 mole of anhydrous aluminum chloride, without hydrogen chloride formation a hydrogen-aluminum-trichloro-3-hydroxy phenolate (referred

REFERENCES:
patent: 4053517 (1977-10-01), Reininger et al.
patent: 4268691 (1981-05-01), Fung et al.
patent: 4508924 (1985-04-01), Mueller et al.
patent: 5068447 (1991-11-01), Gors et al.
Scheilhauser, Pharmazie, vol. 43 (2), pp. 86-90 (1988).
Dauksas et al, Chem. Abst., vol. 109, #17006y (1988).

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