Patent GB-1191869-A (GB)
Title: Production of Amides Substituted on the Nitrogen Atom
IPC: C07D233/32
Filed: 1967-08-22
Abstract: 1,191,869. N-substituted amides and thioamides. BADISCHE ANILIN- & SODAFABRIK A.G. 22 Aug., 1967 [23 Aug., 1966], No. 38626/67. Heading C2C. [Also in Division D1]  N-substituted amides and thio-amides containing one or more groups wherein one or more of the amido nitrogens bears at least one aliphatic radical having a-CHO group attached to the #-carbon atom are prepared by reacting, in stoichiometric proportions for each N-substituent to be introduced, at 0-120‹ C. in the presence of a non- oxidizing strong acid, either: (1) a corresponding amide having at least one hydrogen on the said N atom or atoms with formaldehyde and a CH-acid aldehyde (an aldehyde having at least one hydrogen in the α-position to the -CHO group); (2) a corresponding amide having at least one methylol group on the N atom or atoms, or an etherified derivative thereof, with a CH-acid aldehyde; or (3) a corresponding amide having at least one α-alkylol group on the N atom or atoms, or an etherified derivative thereof, with formaldehyde. The amide starting materials of processes (2) and (3) are prepared by reacting an amide of the kind used in process (1) with a stoichiometric proportion of respectively, formaldehyde or CH- acid aldehyde, N,N-dimethylol-2-oxohexahydropyrimidine being thus prepared by reacting 2- oxohexahydropyrimidine with formaldehyde. The said etherified derivatives are either produced in situ by including an appropriate alkanol in the reaction mixture, or may be prepared by etherification of the isolated N-alkylol amide, N,N<SP>1</SP> - dimethoxymethylimidazolidinone - 2 being prepared by reacting the corresponding dimethylol compound with methanol in the presence of HC1. Novel substituted amides and thio-amides claimed per se have the general formula wherein X is oxygen or sulphur, R<SP>3</SP> and R<SP>4</SP> are the same or different C 1 -C 4  alkyl radicals, and either (1) Y is C 1 -C 8  alkyl, C 6 -C 10  aryl, C 7 -C 12  aralkyl, C 5 -C 6  cycloalkyl, a secondary amino group: where R<SP>5</SP> and R<SP>6</SP> are C 1 -C 8  alkyl or phenyl groups, or -OR<SP>7</SP> where R<SP>7</SP> is C 1 -C 4  alkyl, C 5 -C 6  cycloalkyl, C 2 -C 3  hydroxyalkyl, or C 3 -C 6  alkoxyalkyl ; and R<SP>1</SP> is hydrogen, C 1 -C 4  alkyl, C 6 -C 10  aryl, C 7 -C 12  aralkyl, C 5 -C 8  cycloalkyl, or the radical wherein R<SP>3</SP> and R<SP>4</SP> are as above; or (2) Y and R<SP>1</SP> together form an alkylene chain having 3-5 methylene groups; or (3) Y is the group -NR<SP>5</SP>R<SP>6</SP>; R<SP>5</SP> and R<SP>1</SP> together form an alkylene chain having 2-3 methylene groups which chain may be substituted by up to three C 1 -C 4  alkyl groups; and R<SP>6</SP> is a C 1 -C 8  alkyl radical, a phenyl radical or the radical (II) wherein R<SP>3</SP> and R<SP>4</SP> are as above; or (4) Y is -OR<SP>7</SP> and R<SP>1</SP> and R<SP>7</SP> together form an alkylene chain having 3-5 methylene groups. Examples detail the preparation of 2-oxo hexahydropyrimidyl-N-methyl- N<SP>1</SP>-neopental, -N,N<SP>1</SP>-dineopental, its 5,5-dimethyl-analogue, -N,N<SP>1</SP>-di-(2-ethyl-2-n-butyl-npropanol); pyrrolidone-N-neopental; imidazolidinon - 2 - yl - N,N<SP>1</SP> - neopental; and N,N<SP>1</SP>- dimethyl ureido-N<SP>1</SP>-neopental.