Preparation of pyrroles from ketoximes and acetylenes

Trofimov, B. A., Preparations of Pyrroles from Ketoximes and Acetylenes, 51, 177. 

Preparation of pyrroles from ketoximes and acetylenes 90AHC(51)177. Pyrrole derivatives with phosphorus-containing substituents 93MI1. Pyrroles, general monograph 90CH(48,1)1 92CH(48,2)1. 

Porphyrin derivatives, hydrogenated hydroporphyrins, 43, 73 Preparation of pyrroles from ketoximes and acetylenes, 51, 177... 

So in comparison with DMSO, other nonhydroxylic polar solvents such as HMPA and sulfolane form systems rather less active in catalyzing the synthesis of pyrroles from ketoximes and acetylene. At least, alternative routes based on their application have not been well developed and remain of less preparative importance. In solvents such as ethers, alcohols, and hydrocarbons, the reaction fails to occur (80KGS1299 84MI1). 

This condensation helps one understand why the yield of pyrroles from ketoximes and acetylene is reduced in some cases and consequently allows a more directed search for ways to overcome this obstacle. Optimization of this side reaction would make possible a one-pot preparation of valuable dipyrroles with cyclopropyl or vinyl substituents, such as 98a,c for example. 

The considered reactions enrich the ideas about the processes accompanying synthesis of pyrroles from ketoximes and acetylenes and, when optimized, can gain preparative value as simple approaches to p-terphenyls and 1,3,5-triarylbenzenes. 

Volume 51 of Advances consists of three chapters, V. V. Mezheritskii and V. V. Tkachenko (Rostov-on-Don, U.S.S.R.) review the synthesis of peri-annelated heterocycles, a large and interesting class which has not previously been treated in a systematic fashion. R. M. Acheson (Oxford, U.K.) provides the first detailed survey of 1-hydroxypyrroles and their benzo derivatives, compounds which show an interesting and unusual chemistry. Finally, B. A. Trofimov (Irkutsk, U.S.S.R.) describes the minifold preparative possibility for pyrroles from ketoximes and acetylenes, a reaction discovered by Trofimov and developed by him into a most important entry into pyrrole chemistry. 

Mikhaleva, A.I., B.A. Trofimov, A.N. Vasiliev, and G.A. Komarova. Method for the preparation of 2- or 2,3-substituted pyrroles. 1982. USSR Author s Certificate 979,337. Mikhaleva, A.I., B.A. Trofimov, A.N. Vasiliev et al. 1982. Pyrroles from ketoximes and acetylene. XXII. Dihaloethanes instead of acetylene in the reaction with cyclohexanone oxime. Khim Geterocicl 9 1202-1204. 

Systematic research on this novel synthesis of pyrroles and especially of N-vinylpyrroles from ketoximes and acetylene is in progress. This is expected to lead to not only further extension of the preparative possibilities of the reaction, but also to discovery of new versions and analogs. The increased access to N-vinylpyrroles stimulates more and more synthetic and theoretical investigations in this field as well as work dealing with polymerization and practical application of these compounds (84MI1). For the 20 years since its discovery, the reaction of ketoximes with acetylene has become popular as a reliable preparative tool for wide application in the chemistry of pyrroles. 

This novel synthetic route to pyrroles from ketoximes, based on the use of vinyl chloride instead of acetylene, allowed a one-pot preparation of almost inaccessible 4,5-dihydrobenzo[g]indole (38) and its previously un-... 

In the preparation of pyrroles and N-vinylpyrroles from ketoximes, along with vinyl halides, dihaloalkanes as acetylene equivalents can also be used. Pyrroles and /V-vinylpyrroles are formed in a yield of about 30% in the reaction of ketoximes with dihaloalkanes in the presence of excess alkali metal hydroxide in DMSO (Scheme 60) (79IZV2840). 

Benzofuranyl)pyrroles, 2-(2-thienyl)pyrroles , 2,2 -dipyrroles, 3-(2-pyr-rolyl)indoles , 2-(2-benzimidazolyl)pyrroles and2-(2-, 3- and4-pyridyl)pyrroles were prepared using this method. Reaction of alkynes (for example, propyne) or allene with ketoximes in a superbase system (MOH/DMSO) leads to 2,5-di- or 2,3,5-trisubstituted pyrroles Pyrroles and dipyrroles were synthesized also from corresponding dioximes and acetylene in a KOH/DMSO system It has also been shown that 1,2-dichloroeth-ane can serve as a source of acetylene in pyrrole synthesis. Oxime 52 in the system acetylene/RbOH/DMSO at 70 °C afforded a mixture of three pyrroles 53-55 in low yields (equation 23). The formation of product 53 occurred through recyclization of pyrrolopy-ridine intermediate. ... 

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