Pyrroles from ketoximes and acetylenes

This order of base activity corresponds almost exactly to that observed in the formation of pyrroles from ketoximes and acetylene, evidently for the same causes. The failure of trimethylbenzylammonium hydroxide to catalyze the reaction of vinylation is believed (59MI1 66MI1) to be caused by its lack of coordination. Along with inhibition of the reaction with water, pyridine, o-phenanthroline, and diketones, this indicates the reaction occurs by complex ionic mechanisms in which the participation of the complex ion as an intermediate is possible. 

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). 

Fig. 5. Bench-scale production of pyrroles from ketoximes and acetylene (84M11) 1, reactor 2, extractor 3, stripper 4, extragent collector 5, extragent trap 6, vacuum pump 7, extragent trap 8, explosive valve 9, rotameter 10, refluxer column 11, cooler.

Under these reaction conditions, nitriles can readily transform to the salts of the corresponding carboxylic acids. This may account for the loss of ketoxime without visible signs of resinification occasionally observed in the synthesis of pyrroles from ketoximes and acetylene or its equivalents, i.e., vinyl halides and dihaloethanes (see Section V.B). 

The corresponding 2-hydroxy-2,3-dihydropyrrole (94a), the product of rearrangement of the O-vinyloxime 93a (see Section IV.B), is converted to the 3//-pyrrole 97 under the conditions of the reaction with acetylene (85KGS1573), and this provides more evidence for the O-vinyloxime route to pyrroles from ketoximes and acetylene. 

Recently, (88ZOR1789) in the synthesis of pyrroles from ketoximes and acetylene (KOH/DMSO, 95°C, 5 hr, atmospheric pressure), the formation of dipyrrylethanes (98a-c) along with the normal products, NH-pyrroles and /V-vinylpyrroles, was observed in a number of cases. 

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. 

A thorough investigation of the composition of reaction mixtures has revealed (86MI2) that the KOH/DMSO-catalyzed synthesis of pyrroles from ketoximes and acetylene is accompanied by the formation of Z-l-(2-methylthiovinyl)pyrroles (99), which can be isolated in a yield of about 0.1% (Scheme 48). The pyrroles 99a-c are characterized in detail (86MI3) by H-NMR (Table XXV). I3C-NMR, IR and mass spectra. 

Under optimal or close to optimal conditions for the synthesis of pyrroles from ketoximes and acetylene in the KOH/DMSO system, almost none of the acetylenic alcohols are formed. 

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