Abstract:In this work, new N-substituted 2-aminopyrrole derivatives were synthesized. Initially, some crotonitriles were prepared by condensation of malononitrile with arylmethylketones, which was followed by conversion of them to the bromocrotonitriles. Finally, the synthesis of new N-substituted 2-aminopyrrole derivates were successfully achieved by cyclization of the bromocrotonitriles of (R)-1-phenylethylamine applying Gewald method.
Tertiary propargylamines (such as N,N-dialkylpropargylamines, N-propargylpyrrolidine, -piperidine, and -morpholine), isothiocyanates, and bromoacetonitrile have been shown to be readily available building blocks for the highly selective one-pot construction of rare-functionalized pyrroles, namely so far inaccessible 1-substituted 2-amino-5-(cyanomethylsulfanyl)-1Hpyrroles, in up to 92 % yield. This highly efficient and operationally simple approach includes the initial formation of lithium but-2-ynimidothioate (adduct of monolithiated propargylamine and isothiocyanate), its transformation into potassium buta-2,3dienimidothioate under the action of the t-BuOK/DMSO system (through acetylene-allene isomerization and the exchange by cations), intramolecular cyclization into potassium thienylamide (at � 15°C), followed by its re-cyclization into potassium pyrrolylsulfide at a higher temperature (45-60°C), and the final S-alkylation of the latter with bromoacetonitrile. The total reaction time is 45-60 min.[a] Dr. Scheme 4. Plausible mechanism of pyrrole ring construction from propargylamines 1 and isothiocyanates.Scheme 5. Reaction products obtained from lithiated propargylamine 1 b and 2-(vinyloxy)ethyl isothiocyanate by procedure A. Scheme 6. Plausible mechanism of dipyrromethane 5 formation during synthesis of pyrrole 4 i from propargylamine 1 b and 2-(vinyloxy)ethyl isothiocyanate.
Tertiary propargylamines (such as N,N-dialkylpropargylamines, N-propargylpyrrolidine, -piperidine, and -morpholine), isothiocyanates, and bromoacetonitrile have been shown to be readily available building blocks for the highly selective one-pot construction of rare-functionalized pyrroles, namely so far inaccessible 1-substituted 2-amino-5-(cyanomethylsulfanyl)-1Hpyrroles, in up to 92 % yield. This highly efficient and operationally simple approach includes the initial formation of lithium but-2-ynimidothioate (adduct of monolithiated propargylamine and isothiocyanate), its transformation into potassium buta-2,3dienimidothioate under the action of the t-BuOK/DMSO system (through acetylene-allene isomerization and the exchange by cations), intramolecular cyclization into potassium thienylamide (at � 15°C), followed by its re-cyclization into potassium pyrrolylsulfide at a higher temperature (45-60°C), and the final S-alkylation of the latter with bromoacetonitrile. The total reaction time is 45-60 min.[a] Dr. Scheme 4. Plausible mechanism of pyrrole ring construction from propargylamines 1 and isothiocyanates.Scheme 5. Reaction products obtained from lithiated propargylamine 1 b and 2-(vinyloxy)ethyl isothiocyanate by procedure A. Scheme 6. Plausible mechanism of dipyrromethane 5 formation during synthesis of pyrrole 4 i from propargylamine 1 b and 2-(vinyloxy)ethyl isothiocyanate.
Sequential processing of monolithiated tertiary propargylamines with 2-(vinyloxy)ethyl isothiocyanate and t-BuOKDMSO results in the intro-duction of a highly reactive 2-(vinyloxy)ethyl group at the position 1 of the pyrrole ring thus formed. In this way, a series of new 5-sulfanyl-1-[2-(vinyloxy)ethyl]-1H-pyrrol-2-amines was obtained in a yield of up to 92%. The latter in the presence of t-BuOKDMSO system (110120 C, 1015 min) eliminates vinyl alcohol to give rare-functionalized 1-vinylpyrroles, namely 5-sulfanyl-1-vinyl-1H-pyrrol-2-amines, inaccessible by the known methods.
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