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Synthesis of Unexpected Bifunctionalized Thiazoles by Nucleophilic Attack on Allenyl Isothiocyanate
Author(s) -
Jawabrah AlHourani Baker,
Richter Frank,
Vrobel Kai,
Banert Klaus,
Korb Marcus,
Rüffer Tobias,
Walfort Bernhard,
Lang Heinrich
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201301851
Subject(s) - chemistry , nucleophile , isothiocyanate , moiety , hydrazoic acid , nucleophilic addition , reactivity (psychology) , phenyl isothiocyanate , medicinal chemistry , azide , stereochemistry , organic chemistry , catalysis , medicine , alternative medicine , pathology
Treatment of allenyl isothiocyanate with a variety of nucleophiles leads to 5‐methylthiazoles with a functional group at the 2‐position. The same pattern of reactivity is also seen with N ‐aminophthalimide. In the presence of azide salt, hydrazoic acid, or N , N ‐disubstituted hydroxylamines, however, allenyl isothiocyanate is converted into bifunctionalized thiazoles. We explain the formation of these products by nucleophilic addition at the isothiocyanato moiety followed by ring closure and an N–N or N–O cleavage reaction to generate short‐lived 2‐imino‐5‐methylidenethiazole or 5‐methylidenethiazol‐2‐one. Such intermediates are trapped by addition reactions to give the final heterocyclic compounds. In the case of N , N ‐disubstituted hydroxylamines, the primary addition products with allenyl isothiocyanate can be detected as unstable intermediates by IR and NMR spectroscopy.