Patent GB-652003-A (GB)
Title: Manufacture of naphthyl-propionic acids and derivatives thereof
IPC: C07C59/64
Filed: 1948-07-06
Abstract: Naphthyl-(2)-propionic acids or esters, nitriles or amides of such acids are prepared by reacting a naphthyl-(2)-methyl halide, which contains in the methyl residue at least one hydrocarbon radical and in the 6-position of the naphthalene nucleus an esterified or etherified hydroxyl group, with an a -halogen-acetic acid, which contains in the a -position two hydrocarbon radicals, or with an ester, nitrile or amide of such acid, in the presence of a metal or metal alloy capable of splitting off halogen.  The naphthyl-(2)-methyl halide may contain one alkyl substituent in the methyl residue and is reacted with an a ,a -dialkyl-a -halogen-acetic acid or with an ester, amide or nitrile of such acid.  A suitable ester of a -halogen acetic acid is an a -halogen-isobutyric acid ester.  The b -naphthyl-(2)-propionic acid may be subsequently esterified, e.g. with diazomethane or diazo-ethane or by indirect means using the acid chlorides or alkali salts of the corresponding carboxylic acids, while the b -naphthyl-(2)-propionic acid ester, nitrile or amide may be hydrolysed to the free acid.  When the desired b -naphthyl-(2)-propionic acid contains an esterified or etherified hydroxyl group in the 6-position it may be hydrolysed to a free hydroxyl group, e.g. by alkaline or acidic hydrolysis or in the case of an aralkyl ether a reducing agent, e.g. hydrogen in the presence of a catalyst, may be used.  The hydroxy compounds so obtained may then be esterified, e.g. with acetic, propionic or benzoic acid or etherified, e.g. with methyl, ethyl, propyl or benzyl alcohol.  Metals and metal alloys mentioned capable of splitting off halogen are zinc, magnesium, sodium, the zinc-copper couple and sodium amalgam.  In the examples: (1) b  - (6 - methoxy - naphthyl - 2) - b  - methyl-a ,a -dimethyl-propionic acid methyl ester is prepared which is hydrolysed to the free acid and the methoxy group is then hydrolysed to yield b  - (6 - oxynaphthyl - 2) - b  - methyl - a ,a -dimethyl propionic acid; this acid may be converted to the corresponding acid chloride with oxalyl chloride and then reacted with methanol to yield the methyl ester referred to above, or the acid chloride may be reacted with other alcohols or amino-alcohols, oxyacids, or phenols with the formation of the corresponding ester; (2) b -(6-methoxy-naphthyl-2)-b  - ethyl - a ,a  - dimethyl - propionic acid methyl ester is prepared and is hydrolysed with a solution of caustic potash in methanol to b  - (6 - oxynaphthyl - 2) - b  - ethyl - a ,a -dimethyl-propionic acid; the acid is converted to the corresponding propionic acid ethyl ester with diazo-ethane and the hydroxy group may then be etherified with dimethyl sulphate to yield b  - (6 - methoxy - naphthyl - 2) - b  - ethyl-a ,a -dimethyl-propionic acid ethyl ester which may be converted to the free propionic acid with an ethyl alcohol solution of potassium hydroxide.  The Specification as open to inspection under Sect. 91 refers to the preparation of the above compounds wherein the 6-position of the naphthalene nucleus is substituted with a hydroxyl group or any substituent convertible into a hydroxyl group.  Alkenyl groups, e.g. the allyl group, are mentioned as additional examples of hydrocarbon groups with which the desired propionic acids may be substituted.  When carbon to carbon multiple bonds, particularly those of an aliphatic native, are present in the desired products they may be hydrogenated in known manner.  This subject-matter does not appear in the Specification as accepted.