Patent GB-802841-A (GB)
Title: Process for the manufacture of derivatives of 4-hydroxy-isophthalic acid
IPC: C07C235/46
Filed: 1956-07-02
Abstract: The invention comprises compounds of the general formula <FORM:0802841/IV (b)/1> and salts thereof, wherein of R1 and R2 one represents a hydroxyl group and the other represents an unsubstituted or substituted amino group which may carry lower alkyl or alkenyl, aryl or aralkyl radicals ("lower" indicating not more than 6 carbon atoms in the group), and the preparation thereof by: (a) hydrolysing one of the ester groups in a diester of 4-hydroxy-isophthalic acid and reacting the resulting monoester with ammonia or an amine; (b) reacting 4-hydroxy-isophthalic acid with a heavy metal salt, in the ratio of 1 mol. of 4-hydroxy-isophthalic acid to 1/n mol. of heavy metal salt (n being the valency of the metal), reacting the resulting 3-mono heavy metal salt of 4-hydroxy-isophthalic acid with an alkyl halide and treating the 3-mono-alkyl ester with ammonia or an amine; (c) introducing a carboxyl group into the para-position to the hydroxyl group of a compound having the general formula <FORM:0802841/IV (b)/2> wherein Z1 and Z2 represent hydrogen, lower alkyl or alkenyl, aryl or aralkyl radicals; and (d) subjecting a compound having the general formula <FORM:0802841/IV (b)/3> in the presence of a basic alkali metal compound, or an alkali metal salt of the compound itself, to the action of carbon dioxide at an elevated temperature and pressure.  The resulting products may be converted into salts, if desired.  In examples, dimethyl 4-hydroxyiso-phthalate is either hydrolysed with methanolic potash solution or heated with lead monoxide and water to form the 1-monomethyl ester of 4-hydroxy-isophthalic acid, which is reacted with ammonia to form 4-hydroxy-iso-phthalic acid-1-monoamide; 4-hydroxy-isophthalic acid is heated with silver acetate to form the 3-monosilver salt, which is then reacted with methyl iodide to form the 3-monomethyl ester, which on treatment with ammonia yields 4-hydroxy-iso-phthalic acid-3-monoamide; salicylamide and potassium carbonate are heated with carbon dioxide under pressure to form 3-cyano-4-hydroxy-benzoic acid which is hydrolysed by sulphuric acid to 4-hydroxy-isophthalic acid-3-monoamide, whilst salicylamide, when dissolved in methanolic potassium hydroxide solution, mixed with kieselguhr and sea sand, evaporated to dryness, and heated in a rapid stream of carbon dioxide forms the 4-hydroxy-isophthalic acid - 3 - monoamide directly; similarly salicylic acid methylamide is heated with potassium carbonate and carbon dioxide under pressure to form 4 - hydroxy - isophthalic acid - 3 - monomethylamide directly; and p-hydroxybenzamide is heated with potassium carbonate and carbon dioxide under pressure to form 4-hydroxy-isophthalic acid-1-monoamide, which may be treated with sodium bicarbonate solution and evaporated to form the sodium salt.  A list is given of other substituents (Z1, Z2) on the amide nitrogen atom, including p-chlorophenyl.  Starting materials.  p-Hydroxy - benzamides may be prepared by reacting an ester of p-hydroxy-benzoic acid with ammonia or a corresponding primary or secondary amine; they may be converted into alkali metal salts by evaporation of a solution of the material in an alcoholic alkali metal hydroxide solution.