Patent GB-879576-A (GB)
Title: Improvements in and relating to alkanoic acids and salts thereof
Filed: 1958-08-28
Abstract: The invention comprises acids and esters of the general formula <FORM:0879576/IV (b)/1> (wherein R1 represents a hydrogen atom or a C1-4 alkyl group, R2 represents a hydrogen atom or a group COOR1, R3, R4 and R5 each represents a hydrogen atom or a C1-4 alkyl group, Ar represents a phenyl group which is unsubstituted or substituted by halogen atoms or methyl, methoxy, 3,4-methylendioxy or hydroxy groups, and n is 0, 1, 2 or 3, at least one of R1, R2 and R3 being other than hydrogen when n is 0) and salts of the above acids, e.g. derived from sodium and calcium hydroxide, and acid addition salts of the above acids and esters, e.g. prepared from inorganic and organic acids such as hydrochloric, hydrobromic, phosphoric, acetic, benzoic, tartaric, citric and methanesulphonic acids, and the preparation thereof by: (a) (when R2 is hydrogen) catalytically reducing an oxime of the general formula <FORM:0879576/IV (b)/2> (wherein X represents COOH) and, if desired, alkylating and esterifying the product; (b) (when R4 is hydrogen) catalytically hydrogenating a compound of the general formula <FORM:0879576/IV (b)/3> (wherein R11 represents a C1-4 alkyl group and R21 a hydrogen atom or a group COOR11) and, if desired, monoalkylating the product, and further, if desired, hydrolysing and, if necessary and desired, decarboxylating the alkylation product, and, if desired, esterifying the hydrolysed product.  The compounds wherein n is 0 or 1 and R1 is C1-4 alkyl can also be prepared by reacting esters of the general formulae <FORM:0879576/IV (b)/4> with nitroalkanes of the general formula R4-CH2-NO2 to form compounds of the general formulae <FORM:0879576/IV (b)/5> and subjecting these to catalytic hydrogenation and the products to reductive alklyation if desired.  The compounds in which R1 and R2 are both hydrogen can also be prepared by treating compounds of the general formula <FORM:0879576/IV (b)/6> with an alkali metal hypohalite, and, if desired, reductively alkylating the products.  The compounds in which R1 is hydrogen can also be prepared by reacting compounds of the general formula <FORM:0879576/IV (b)/7> with compounds of the general formula <FORM:0879576/IV (b)/8> (wherein Am represents an imido group or an imido group which may be N-substituted by a C1-4 alkyl radical) in the presence of an alkaline condensing agent, and hydrolysing and, if desired, alkylating the product.  The products are useful as fast acting central nervous system stimulants.  Phenylacetic acid esters of the general formula <FORM:0879576/IV (b)/9> wherein R12 represents the COOR11 radical, and R11, R5 and n have the above significance are prepared, for example, by alkylating phenyl malonic acid diethyl esters with o -chloroalkyl cyanides.  In examples diethyl phenyl malonate and chloracetonitrile and a -chloropropionitrile are reacted to form ethyl 2-carbethoxy-3-cyano-2-phenyl-propionate and -butyrate respectively.  3-Oximino-2-phenylbutyronitrile is prepared by reacting a -phenyl-acetoacetonitrile and hydroxylamine hydrochloride. Ethyl 2-(p-methoxyphenyl)-cyanoacetate is prepared by reacting diethyl carbonate and p-methoxyphenyl-acetonitrile in the presence of sodium.  Ethyl a -phenyla -propyl-cyanoacetate is prepared by reacting diethyl carbonate and a -phenylvaleronitrile in the presence of sodium.