Cyanoacetamide → HCID 178429416, compound

6-Hydroxypyrid-2-ones (formula I, R=hydrogen) which are unsubstituted at the pyridone nitrogen have been known for a long time. They were first discovered and described by Guareschi in the reaction of β-ketocarboxylic acid esters with cyanoacetamide (Mem. Accad. Torino cl. sci. fis. mat. e nat. [2], volume 46, page 11; Chemisches Zentralblatt 1896 I, 601). Other authors have obtained this compound by cyclising the reaction product of acetoacetic acid ethyl ester with malodinitrile (for example Kasturi, T.R.; Sharma, V.K.; Srinivasan, A.; Subrahmanyam, G.; Tetrahedron 29 (1973) 24, 4,103-09 and Gudriniece, E.; Rigerte, B.; Latv. PSR Zinat. Akad. Vestis, Kim. Ser. (1974) (2), (239-40). A process for the preparation of 5-cyanopyrid-6-ones by reacting halogenoacetic acid esters with nitrogen compounds and subsequently reacting the reaction mixture with alkali metal cyanides and then with dicarbonyl compounds is described in German Document No. 2,531,035 open for Inspection. This process constitutes a modification of the known Guareschi process - the reaction of cyanoacetamide with acetoacetic ester - in which, however, there is put in as an initial stage the preparation of the cyanoacetamide from chloroacetic acid by esterifying the latter, ammonolysing the ester to give chloroacetamide and reacting this product with sodium cyanide to give cyanoacetamide. Subjecting acetoacetic acid ethyl ester and cyanoacetamide to a condensation reaction in the presence of piperidine or potassium hydroxide to give 3-cyano-2,6-dihydroxy-4-methylpyridine, in order to improve the yield of the valuable end product, has also already been described (Journal of Organic Chemistry, volume 25 (1960), pages 560-564). Finally, a process for the preparation of N-alkylsubstituted 6-hydroxypyrid-2-ones, in which the cyanoacetic acid ethyl ester, acetoacetic acid ethyl ester and an alkylamine are reacted in alkanoic solution at 110° to 120° C. in an autoclave is known from German Document No. 1,956,142 open for inspection. In this case the amine is employed in a pure form and, after the completion of the reaction, the alkanol used as the solvent must be removed by distillation. If, for example, 1,4-dimethyl-3-cyano-6-hydroxypyrid-2-one is prepared by the instructions of this publication by reacting 1 mol of cyanoacetic acid ethyl ester, 1 mol of acetoacetic acid ethyl ester, 2 mols of methylamine and approx. 700 ml of n-butanol as solvent at a temperature of 115° C., a yield of about 70% is obtained after a reaction time of 4 hours, approx. 79% after a reaction time of 8 hours and approx. 80% after a reaction time of 16 hours. It is found in this connection that this known process evidently tends towards a limiting yield value at about 80% of theory, which is not exceeded even with a considerably prolonged reaction time. Apart from the fact that reaction times of 8 or 16 hours lead to a very poor space-time yield for the process, 80% of theory is also unsatisfactory for an industrial process, since not only must a loss of end product be accepted, but also the 20% of starting materials and by-products have to be eliminated in an ecologically satisfactory manner, which causes additional costs.

ORD record

ord-e855530b78214f129684f7693201d0e8

Source dataset

uspto-grants-1981_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04284782