Patent GB-1179000-A (GB)
Title: A process for preparing 1,4-naphthoquinones and chemical intermediates used therein
IPC: C07C46/00
Filed: 1967-10-23
Abstract: 1,179,000. Naphthoquinones and intermediates therefor. STERLING DRUG Inc. 23 Oct., 1967 [25 Oct., 1966 (2)], No. 48161/67. Heading C2C. [Also in Division C4] A process for preparing the antimalarial agent 2 - hydroxy - 3 - (8 - cyclohexyloctyl or 7- cyclohexylheptyl) - 1,4 - naphthoquinone comprises reacting 2-(8-cyclohexyloctyl or 7-cyclohexylheptyl) - 1,4 - naphthoquinone with a peroxide under alkaline conditions to form 2-(8- cyclohexyloctyl or 7-cyclohexylheptyl) - 1,4 - naphthoquinone-2,3-oxide and hydrolysing the 2,3- oxide under acidic conditions. 2 - (8 - Cyclohexyloctyl or 7 - cyclohexylheptyl)- 1,4-naphthoquinone is obtained by reacting 2-(8- cyclohexyloctyl or 7 - cyclohexylheptyl) - 1 - naphthol (prepared by treating the cyclohexyl-octanoyl- or -heptanoyl-naphthol with amalgamated zinc in the presence of methanol and concentrated hydrochloric acid) with a diazotized salt of sulphanilic acid to form 2-(8-cyclohexyloctyl or 7 - cyclohexylheptyl) - 4 - (4 - sulphophenylazo) - 1-naphthol; reducing the azo compound to form 4 - amino - 2 - (8 - cyclohexyloctyl or 7 - cyclohexylheptyl) - 1 - naphthol; oxidizing said 4 - amino compound to form 2-(8-cyclohexyloctyl or 7 - cyclohexylheptyl) - 1,4 - dihydro - 4 - imino - 1-oxonaphthalene; and hydrolysing said 4-imino compound, usually in the form of the chromate or sulphate salt, under acidic conditions. The foregoing 1,4-naphthoquinones are also obtained by oxidizing the foregoing 2-substituted naphthols or 4-amino compounds utilizing chromium trioxide. 2 - (8 - Cyclohexyloctanoyl or 7 - cyclohexylheptanoyl) - 1 - naphthol is obtained by the interaction of α-naphthol and the appropriate cyclohexylalkanoic acid in the presence of boron trifluoride etherate; 8-cyclohexyloctanoic acid is obtained by reacting either 8-cyclohexyl-7-ketooctanoic acid (obtained by treating 2-cyclohexylacetylcyclohexanone with potassium hydroxide) or 8 - cyclohexyl - 6 - keto - octanoic acid (obtained by treating 2-[3-cycloherylpropanoyl]- cyclopentanone with KOH) with hydrazine hydrate followed by KOH and final treatment with concentrated hydrochloric acid; 7-cyclohexylheptanoic acid is similarly obtained from 7 - cyclohexyl - 6 - keto - heptanoic acid (obtained from 2 - cyclohexylacetyl - cyclopentanone with KOH); the foregoing cyclopentanones and cyclohexanone are obtained by appropriate acylation of a 1-substituted-cyclopentene or -cyclohexene (the 1-substituent in the case of the cyclopentene is morpholino-, piperidino-, and diethylamino-; in the case of the cyclohexene it is piperidino-, pyrrolidino-, morpholino- and dimethyl-, diethyl-, di-n-propyl- and di-n-hexylamino-) to give first a 2-cyclohexylacetyl- or 2-(3- cyclohexylpropanoyl)- 1 - substituted cyclopentene or -cyclohexene which is converted on acid hydrolysis to the desired cyclopentanone or cyclohexanone. The foregoing 1-substitutedcyclopentenes and -cyclohexenes are obtained by reacting cyclopentanone or cyclohexanone with the appropriate secondary amine in the presence of p-toluenesulphonic acid.