Patent GB-1098355-A (GB)
Title: Method of preparation of dihydropyrrole derivatives
IPC: C07D207/34
Filed: 1964-12-21
Abstract: Dihydropyrroles of the general formula <FORM:1098355/C2/1> <FORM:1098355/C2/2> are obtained by contacting an olefinic compound of the formula (R)2C=C(R)2 with an azlactone or mesoionic azlactone of the respective general formula <FORM:1098355/C2/3> <FORM:1098355/C2/4> wherein each of R, R1, R2 and R3 represents hydrogen or monovalent aliphatic, cycloaliphatic, aromatic or heterocyclic groups attached to the ring atoms through a carbon to carbon bond or in the case when R3 is other than hydrogen through a carbon to nitrogen bond, also R may be cyano and R1 and R3 can together form an alkylene group, but in the reaction with a mesoionic azlactone at least one of the substituents R must be a hydrogen atom. The reactants are suitably contacted at between 0 DEG  and 140 DEG C., preferably between 50 DEG  and 140 DEG  C., and the reaction is preferably carried out in an inert solvent, especially benzene, toluene, xylene or dioxane. The process may also be conducted in an inert atmosphere, e.g. of nitrogen or argon.  The azlactone may be derived from an appropriate a -amino-carboxylic acid and the azlactone or mesionic azlactone is preferably formed in situ by starting with an appropriate a -amino carboxylic acid containing primary or secondary amino groups or its N-acyl derivative with the aid of an acid anhydride, e.g. acetic anhydride, and the resulting azlactone or mesoionic azlactone then reacts immediately with the unsaturated compound present as the other reactant.  Substituents may be present on the various R to R3 groups and the group R1 may be any natural alpha-amino acid residue. Examples of the group R2 are methyl, ethyl, n-pentyl, isopropyl, cyclohexyl, phenyl, b -pyridyl, p-chlorophenyl, o-nitrophenyl, betanaphthyl and p-acetaminophenyl. The unsaturated reactant may be e.g. propylene, cyclopentene, 1-hexene, norbornene, styrene, acenaphthylene, stilbene, 1,2-dihydronaphthalene, indene, butadiene, isoprene, phenyl butadiene, chloroprene, a cinnamic, acrylic, fumaric, maleic or mesaconic ester, ethylenetetracarboxylic ester, benzalacetone, dibenzoylethylene, benzalacetophenone, acrylonitrile, methacrylonitrile, fumaric acid dinitrile, 1 - phenyl phenyl - 2 - nitroethylene or cinnamonitrile. Several examples are given and the invention also includes as new products compounds of the given general formulaae in which R, R1, R2 and R3 are as defined above with the proviso that (a) not more than two of the groups R, R1, R2 and R3 represent hydrogen, (b) R1 and R3 can also together form an alkylene group, and (c) when the ring nitrogen is unsubstituted then R1 and R2 must always be aryl.  The invention also includes per se the following specific compounds which are products of certain of the examples: (1) dimethyl 2,5 - diphenyl - D 1 - pyrroline - 3,4 - dicarboxylate, (2) 2,5 - diphenyl - 3 - cyano-D 1-pyrroline, - 4 - carboxylate, (4) 1 - methyl - 2,3,3,5 - tetraphenyl (3) ethyl 2,3,5-triphenyl-D 1-pyrroline-4 - carboxylate, (4) 1 - methyl - 2,3,3,5 - tetraphenyl - 2,3 - dihydropyrrole, (5) dimethyl 1 - methyl - 2,5 - diphenyl - 2,3 - dihydropyrrole - 3,4 - dicarboxylate, (6) 1 - methyl-2,5-diphenyl - 3,4 - dibenzoyl - 2,3 - dihydrpyrrole, (7) methyl 1,4 - dimethyl - 2,5 - diphenyl-D 2-pyrroline - 3 - carboxylate, (8) dimethyl 1,4-dimethyl - 2,5 - diphenyl - D 2 - pyrroline - 3,4-dicarboxylate and (9) dimethyl 2,5-dimethyl-1 - cyclohexyl - D 2 - pyrroline - 3,4 - dicarboxylate. In one of the examples (Example 15), 1 - methyl - 2,5 - diphenyl - 3 - n - butylpyrrole is obtained by reacting anhydro-5-hydroxy-3-methyl-2,4-diphenyl-oxazolium hydroxide with n-hexene-(1), elimination of hydrogen occuring on working up the product.