Multicomponent reaction for the first synthesis of 2,2-dialkyl- and 2-alkyl-2-aralkyl-5,6-diaryl-2H-1,3-thiazines as scaffolds for various 3,4-dihydro-2H-1,3-thiazine derivatives

Abstract

A two-step sequence for the synthesis of various 3,4-dihydro-2H-1,3-thiazines is presented. In the first step, 2H-1,3-thiazines were prepared by a new multicomponent reaction (MCR). Starting from β-chlorovinyl aldehydes, this MCR offers an efficient and facile access to 2,2-dialkyl- and 2-alkyl-2-aralkyl-5,6-diaryl-2H-1,3-thiazines. The potential of these products in subsequent reactions was verified by the conversion to 3,4-dihydro-2H-1,3-thiazine-containing bisamides, β-lactams, and methoxy amides.

Microwave-Assisted Asinger Synthesis of Thiazolines

“…MeOH incompatibility of aqueous ammonia with the other components, specially 2-bromoketone, affording some degradation products related to competition in nucleophilic substitution on 2-bromoketones which resulted sensitive to ammonia. This behavior was kept with the introduction of other solvents (entries 4-7) at different temperatures (entries 8-10) as well as diverse ammonia sources (entries [11][12][13][14][15][16][17][18].…”

“…On the other hand, since its discovery in the late fifties [10][11][12], Asinger reaction has showed the distinctive advantages provided by multicomponent reactions applied to the synthesis of cyclic compounds [13][14][15][16][17], however, these apparent benefits are missed probably due to the few starting materials reported in literature which are compatible (and sometimes soluble) with aqueous ammonia, in addition to reaction temperatures close to ambient conditions or lower [18,19].…”

Steroidal Pyrimidines and Dihydrotriazines as Novel Classes of Anticancer Agents against Hormone-Dependent Breast Cancer Cells

“…Our interest in the preparation of structurally diverse heterosteroids lead to a need for a facile flexible strategy, in which a common intermediate can be used in a conjunctive fashion to form an array of N -heterocycles attached or fused to the steroid core. Hence, we turned to β-chlorovinyl aldehydes, which are readily available by the Vilsmeier–Haack reaction (Tasneem, 2003 ) and proved to be highly reactive ambident electrophiles (Bera et al, 2008 ; Bezboruah et al, 2013 ; Brockmeyer et al, 2014 ; Kroger et al, 2015 ). Recently, we have reported the synthesis of steroidal pyridazines (Komkov et al, 2015 ; Volkova et al, 2016 ), thiadiazoles (Zavarzin et al, 2013 ), and 4,5-disubstituted pyrimidines (Komendantova et al, 2017 ) via condensation of β-chlorovinyl aldehydes with bis-nucleophiles such as oxamic acid thiohydrazides and amidines.…”

Efficient Synthesis of 4‐ and 5‐Substituted 2‐Aminopyrimidines by Coupling of β‐Chlorovinyl Aldehydes and Guanidines

“…They are stable for storage in solution and do not require any special conditions for preparation. Chlorovinyl aldehydes proved to be highly reactive ambident electrophiles that easily undergo a variety of cyclization reactions, especially with compounds having bis‐nucleophilic properties . Inspired by these previous studies and in continuation of our research on the synthesis of N‐heterocycles, we elaborated a conceptually simple, practical and general methodology for the synthesis of 4,5‐substituted pyrimidines based on the condensation of β‐chlorovinyl aldehydes with amidines under mild conditions.…”