Patent GB-632341-A (GB)
Title: Manufacture of acyl derivatives of acetoacetic acid amides
Filed: 1947-07-29
Abstract: Acyl derivatives of amides of acetoacetic acid are manufactured by reacting two equivalents of an alkali metal compound of an acetoacetic amide, of the general formula CH3COCH(Me)CONHR (wherein Me represents an alkali metal and NHR the residue of a diazotizable amine), with one equivalent of an acylating agent, whereby half of the acetoacetic amide alkali metal compound is converted to the free amide and the other half acylated to form a compound of the general formula <FORM:0632341/IV (b)/1> (wherein R1CO represents the acyl radical of the acylating agent used), or a tantomeric form thereof. The products of the reaction may be separated by utilizing their different solubilities by suitable choice of solvent for the reaction, and the alkali metal compound of the diacylacetic amide may, if desired, be converted to the free amide.  Thus the reaction may be carried out in a water-immiscible solvent (e.g. benzene or chlorobenzene) into which the acetoacetic amide may be introduced, then converted to its alkali metal compound and this treated with the acylating agent, the regenerated acetoacetic amide remaining in solution whilst the alkali metal compound of the diacylacetic amide is precipitated and may be separated by filtration and converted to the free amide, e.g. by solution in water and acidification. Alternatively the reaction may be effected in an aqueous medium, in which case the free acetoacetic amide is precipitated whilst the alkali metal compound of the diacylacetic amide remains in the aqueous solution, from which, after filtration, the free amide may be obtained by acidification.  In this latter case it is possible to add a further quantity of alkali metal hydroxide and acylating agent to convert a further amount of acetoacetic amide, and this process may be repeated several times until substantially all the acetoacetic amide has reacted with an equivalent quantity of acylating agent. The diazotizable amines from which the acetoacetic amides are derived may be primary mono- or di-amines of the aromatic or heterocyclic series, e.g. aniline, o- or m-toluidine, o-, m- or p-chloraniline, o- or p-anisidine, o- or p-phentidine, 2 : 5-dimethoxy-or diethoxy-aniline, 2 : 4-dimethoxy-4-chloraniline, 2-methoxy- or ethoxy-5-methylaniline, benzidine, o-tolidine, dehydrothiotoluidine, 2 - aminothiazole, 2 - aminobenzthiazole or 2-amino-6-methoxybenzthiazole.  Suitable acylating agents are acid chlorides and anhydrides, preferably containing an acyl radical of more than two carbon atoms, e.g. higher fatty acid chlorides such as stearic acid chloride, or chlorides of aromatic or araliphatic carboxylic acids such as benzoic, o-, m- or p-chlorobenzoic, 2 : 5-dichlorobenzoic, m- or p-nitrobenzoic, 3-nitro-4-methoxybenzoic, o-toluic or cinnamic acid, naphthalene-1- or 2- carboxylic acid, diphenyl-4 : 41-dicarboxylic acid, phthalic acids, especially terephthalic acid, phenylacetic or phenoxyacetic acid.  Examples describe the use of certain of the foregoing starting materials in both modifications of the process.  The products are useful as intermediates for the dyestuff industry, especially when employed in the process described in Specification 20391/47, as open to inspection under Sect. 91).