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[EN] 971,700. Araliphatic acids, esters, alcohols and amines. BOOTS PURE DRUG CO. Ltd. Jan. 12, 1962 [Feb. 2, 1961], No. 3999/61. Heading C2C. [Also in Division A5] The invention comprises compounds of general formula which are (A) acids, and their inorganic and organic salts, wherein X is COOH, R1 is isobutyl, s-butyl, pentyl (other than n-pentyl), 1-methylcyclohexyl, 1-ethylcyclohexyl or cycloheptyl, and R2 is hydrogen or methyl, and if R2 is methyl R1 may also be ethyl, n-propyl, t-butyl or cyclohexyl, (B) alcohols wherein X is CH 2 OH, R1 is isobutyl, s-butyl, pentyl (other than n-pentyl or t-pentyl); 1-methylcyclohexyl, 1-ethylcyclohexyl or cycloheptyl, and R2 is hydrogen or methyl, and, if R2 is methyl, R1 may also be n-propyl, iso-propyl, t-butyl or t-pentyl, (C) esters wherein X is COOR3, R1 is isobutyl, pentyl (other than n-pentyl or t-pentyl), cyclohexyl, 1-methylcyclohexyl, 1-ethylcyclohexyl or cycloheptyl, R2 is hydrogen or methyl, and R3 is alkyl (1-8C) or optionally N-alkylated aminoalkyl (2-8C), and if R3 is other than ethyl or if R2 is methyl, R1 may also be s-butyl, t-butyl or t-pentyl, (D) amines wherein X is CH 2 NH 2 , R1 is isobutyl; s-butyl, t-butyl, pentyl (other than n-pentyl), cyclohexyl, 1-methylcyclohexyl, 1-ethylcyclohexyl or cycloheptyl, and R2 is hydrogen or methyl. Methods for their preparation are enumerated. In examples: (1) 4-R 1-acetophenones are refluxed with sulphur and morpholine and treated to yield acids, (2) acids with alcohols form esters, (3) esters are hydrolyzed to acids, (4) 4-R1- phenylacetyl chlorides are reacted with alcohols to yield esters, (5) 4-R1-phenylacetamides are reduced with lithium aluminium hydride to amines, (6) ethyl 4-R 1-phenylacetates are treated with ethyl carbonate yielding ethyl 4-R1-phenylmalonates from which the c-methyl ester may be obtained with methyl iodide and which is hydrolyzed to give via the sodium salt the substituted malonic acid which on decarboxylation yields acids, (7) 4-R 1-cyclohexanones are reacted with ethyl bromoacetate and zinc giving ethyl 4-R1-cyclohex-1-enylacetates which on dehydrogenation yield esters, (8) 4-R1-benzyl chlorides with sodium cyanide give nitriles which on hydrolysis yield acids, (9) 4-R1-benzenes with ethyl oxalyl chloride and aluminium chloride give ethyl 4-R 1-phenylglyoxalates which on hydrogenation and hydrolysis yield acids, (10) esters are reduced with lithium aluminium hydride to yield alcohols.
[EN] The invention comprises compounds of general formula <FORM:0971700/C1/1> which are (A) acids, and their inorganic and organic salts, wherein X is COOH, R1 is isobutyl, s-butyl, pentyl (other than n-pentyl), 1-methylcyclohexyl, 1-ethylcyclohexyl or cycloheptyl, and R2 is hydrogen or methyl, and if R2 is methyl R1 may also be ethyl, n-propyl, t-butyl or cyclohexyl, (B) alcohols wherein X is CH2OH, R1 is isobutyl, s-butyl, pentyl (other than n-pentyl or t-pentyl), 1-methylcyclohexyl, 1-ethylcyclohexyl or cycloheptyl, and R2 is hydrogen or methyl, and, if R2 is methyl, R1 may also be n-propyl, iso-propyl, t-butyl or t-pentyl, (C) esters wherein X is COOR3, R1 is isobutyl, pentyl (other than n-pentyl or t-pentyl), cyclohexyl, 1-methylcyclohexyl, 1-ethylcyclohexyl or cycloheptyl, R2 is hydrogen or methyl, and R3 is alkyl (1-8C) or optionally N-alkylated aminoalkyl (2-8C), and if R3 is other than ethyl or if R2 is methyl, R1 may also be s-butyl, t-butyl or t-pentyl, (D) amines wherein X is CH2NH2, R1 is isobutyl, s-butyl, t-butyl, pentyl (other than n-pentyl), cyclohexyl, 1-methylcyclohexyl, 1-ethylcyclohexyl or cycloheptyl, and R2 is hydrogen or methyl. Methods for their preparation are enumerated. In examples: (1)4-R1-acetophenones are refluxed with sulphur and morpholine and treated to yield acids, (2) acids with alcohols form esters, (3) esters are hydrolyzed to acids, (4) 4-R1-phenylacetyl chlorides are reacted with alcohols to yield esters, (5) 4-R1-phenylacetamides are reduced with lithium aluminium hydride to amines, (6) ethyl 4-R1-phenylacetates are treated with ethyl carbonate yielding ethyl 4-R1-phenylmalonates from which the c-methyl ester may be obtained with methyl iodide and which is hydrolyzed to give via the sodium salt the substituted malonic acid which on decarboxylation yields acids, (7) 4-R1-cyclohexanones are reacted with ethyl bromoacetate and zinc giving ethyl 4-R1-cyclohex-1-enylacetates which on dehydrogenation yield esters, (8) 4-R1-benzyl chlorides with sodium cyanide give nitriles which on hydrolysis yield acids, (9) 4-R1-benzenes with ethyl oxalyl chloride and aluminium chloride give ethyl 4-R1-phenylglyoxalates which on hydrogenation and hydrolysis yield acids, (10) esters are reduced with lithium aluminium hydride to yield alcohols. ALSO: Therapeutic compositions comprise a compound of general formula <FORM:0971700/A5-A6/1> wherein R1 is ethyl, propyl, butyl, pentyl (except n-pentyl), alkenyl (2-4C), alkoxy (2-3C), allyloxy, phenoxy, phenylthio, or cycloalkyl (5-7C) optionally substituted by methyl or ethyl in 1-position; R2 is hydrogen or methyl; X is COOH, COOR3 (where R3 is alkyl (1-8C) or optionally N-alkylated aminoalkyl (2-8C)), COOM (where M is NH4 or a single equivalent of a nontoxic metallic cation), COOH.B (where B is nontoxic organic base), CONH2, CH2NH2, or CH2OR4 (where R4 is hydrogen or alkanoyl (1-3C)), in association with a solid or liquid pharmaceutically acceptable diluent or carrier. Administration, in humans and animals, may be oral, parenteral or topical, and compositions mentioned are capsules, tablets, lozenges, effervescent granules, mixtures, elixirs, syrups, suspensions, ointments, creams and lotions. The compounds have analgesic and antipyretic activity. The Provisional Specification relates to such compositions containing compounds of general formula 4-R1-Ph-CR2R3-X wherein R1 represents alkyl (2-4C), branched alkyl (5-8C), alkoxy (2-4C), alkyleneoxy (2-4C), phenoxy, phenylthio, or cycloalkyl (4-8C); Ph represents phenyl; R2 represents hydrogen, R3 represents hydrogen or alkyl (1-3C), or R2 and R3 together represent methylene; X represents COOR4 (where R4 is hydrogen or alkyl (1-4C)), COOM (where M is ammonium or an equivalent of a nontoxic metallic cation), COOH.B (where B is a nontoxic organic base), CONR5R6 (where R5 and R6 are each hydrogen or alkyl (1-4C) or with the nitrogen atom form a heterocyclic ring), CHO, CH2NH2, and CH2OR7 (where R7 is alkyl (1-8C) or alkanoyl (1-4C)). Additional compounds enumerated are 4-ethyl- and 4-n-butyl - phenylacetic acid, 4 - t - butylphenyl-N - ethylacetamide, 4 - t - butylphenylacetmorpholide, and a - 4 - t - butylphenylbutyric and -pentanoic acids; tablets are prepared containing 4-t-butylphenylacetic acid. |
