Patent GB-1099500-A (GB)
Title: Preparation of pyrrole derivatives
IPC: C07D207/34
Filed: 1964-12-21
Abstract: Pyrroles of the general formula <FORM:1099500/C2/1> are obtained by contacting an acetylenic compound of the formula R3C=CR4 with an azlactone or mesoionic azlactone of the respective general formulae <FORM:1099500/C2/2> wherein each of R1 to R5 is hydrogen or a monovalent aliphatic, cycloaliphatic or heterocyclic group attached to the ring carbon atom through a carbon to carbon bond or in the case when R5 is other than hydrogen through a carbon to nitrogen bond, with the proviso (a) that when an azlactone of the first formula is used R5 in the resulting pyrrole is hydrogen, and (b) R1 and R5 can together form an alkylene group. The radicals R1 to R5 may be substituted, e.g. by amino, carbalkoxy, CN, halo, isocyanato, nitro, sulpho or thio or other group containing C and H and O, N, or S.  The substituent R1 may also be any natural alpha-aminocarboxylic acid residue.  The reaction is preferably effected at 0 DEG  to 140 DEG  C. and preferably in an inert solvent especially benzene, toluene, xylene or dioxane and the process can be conducted in an inert atmosphere, e.g. of nitrogen or argon.  The azlactone or mesoionic azlactone may be formed in situ in the reaction system from an appropriate alpha-amino carboxylic acid having primary or secondary amino groups or its N-acyl derivative by cyclization by means of an acid anhydride, e.g. acetic acid, and then reacts immediately after its formation with the acetylenic reactant also present.  The acetylenic compound may be acetylene itself or a substituted acetylene, e.g. a propiolic ester, acetylene dicarboxylic ester, dibenzoylacetylene, phenylpropiolic ester, p-chlorophenyl-acetylene, 1 - phenyl - 2 - acetyl - acetylene, 1 - hexyne or propargyl acetate.  Several examples are given and the invention also includes as novel products substituted pyrroles of the given general formula in which each of R1 to R5 are hydrogen or a monovalent aliphatic, cycloaliphatic, aromatic or heterocyclic group attached to the ring carbon atom through a carbon to carbon bond or when R5 is other than hydrogen through a carbon to nitrogen bond, with the proviso that (a) at least one of R3 and R4 is an alkoxycarbonyl group, (b) at least one of R1 and R2 is other than hydrogen, and (c) R1 and R5 can together form an alkylene group. The invention also includes per se the following specific products which are products of certain of the examples:-(1)  dimethyl 2-phenyl-5-methyl - pyrrole - 3,4 - dicarboxylate, (2)  dimethyl 2,5 - diphenylpyrrole - 3,4 - dicarboxylate, (3)  dimethyl 2-(0-nitrophenyl)-5-phenylpyrrole - 3,4 - dicarboxylate, (4) dimethyl-2-(p-methoxyphenyl) - 5 - phenylpyrrole - 3,4 - dicarboxylate, (5) methyl 2,5-diphenylpyrrole-3-carboxylate, (6) 2,3,5-triphenyl-4-acetylpyrrole, (7) 2,3,5-tri-phenylpyrrole, (8) dimethyl 2-(a -naphthyl) - 5 - phenylpyrrole - 3,4 - dicarboxylate, (9)  dimethyl 2-phenyl-5-p-chlorophenyl-pyrrole 3,4-dicarboxylate, (10) 2,3,4,5 - tetraphenyl - 1 - methylpyrrole, (11) 2,5 - diphenyl - 1 - methyl - 3 - n - butylpyrrole, (12)  1,3 - diphenyl 2,5 - dimethylpyrrole, (13) 1,2 - dimethyl 3,5- (or 4,5-) diphenylpyrrole, and (14) 2,3,5 - triphenyl - 1 - methyl - 4 - benzoyl - pyrrole.