A microwave induced cyclisation of α‐phenylsulfonyl‐enaminoacrylates for the preparation of 4‐aryl‐4H‐1,4‐benzothiazine 1,1‐dioxide derivatives

Abstract

Several 4-aryl-4H-1,4-benzothiazine 1,1-dioxide derivatives have been prepared in good yields by microwave promoted cyclisation of α-phenylsulfonyl-enaminoacrylate intermediates in basic media. Benzothiazines were obtained without the use of a catalyst in short reaction times.J. Heterocyclic Chem., 42, 1007Chem., 42, (2005.During the course of our research toward the synthesis of novel 4-aryl-4H-1,4-benzothiazine 1,1-dioxide derivatives [1-3], we decided to explore some new alternatives for the crucial cyclisation step of the α-phenylsulfonyl enaminoacrylate intermediates to the corresponding benzothiazines. Despite this kind of cyclisation is relatively easy for their isostere counterpart α-phenylcarbonyl enaminoacrylates for the synthesis of 1-arylquinolones by the widely employed Groche's methodology [4], it was not achieved in high yields for the preparation of 4-aryl substituted 1,4-benzothiazines unless a 5% silver nitrate was used as a catalyst (Scheme 1) [2]. The silver nitrate, may complex the chlorine atom of the aromatic ring lowering the energy of the transition state of the aromatic substitution bringing the reaction to completion in high yields. Recently, a great interest in microwave promoted reactions has emerged in organic synthesis [5], it has been used for the preparation of heterocycles [5-10] and valuable organic intermediates in short reaction times without the use of costly reagents and catalysts. This available technology has led us to test microwave irradiation for the synthesis of organofluorine aromatic amides [11] and the cyclisation of enaminoacrylates to 4-aryl-4H-1,4-benzothiazines (4 a-i) without the aid of catalyst (Scheme 2), standard conditions were established varying the microwave power source and the reaction time (Table 1). Our results show that microwave irradiation is a good alternative for the cyclisation step instead of use of a catalyst. Although a slightly lower, comparable yields of the benzothiazines were obtained and the methodology is also affordable even for the cyclisation of hindered ortho-substituted acrylates (3f, 3i). In view that nucleophilic aromatic substitution (S N Ar) reactions have not been explored much under microwave irradiation conditions [12], this work represents a new contribution to the knowledge of the application of microwave synthesis to achieve this goal efficiently in short reaction times.

Modelling One-Pot Method for Synthesis of 2,3-Dihydro-1<i>H</i>-pyrrolo[2,1-<i>c</i>][1,4]benzothiazine 5,5-Dioxides and Their Homologues

“…The promising approach is also the cyclization of 2-[(2-halogenophenyl)sulfonyl]ethylenamines containing electronwithdrawing group A in the presence of bases [20][21][22][23][24][25][26] (Figure 1).…”

“…The most significant limitation of this method is mainly concerned with the leaving halogen (X) activity. For instance, the cyclization of orto-chloroderivatives (X = Cl) could be successfully carried out only in the presence of strong bases [20], silver nitrate [22,23], potassium carbonate-crown-ether [21] or requires the application of microwave technology [24,25]. In the case of fluoroderivatives (Х = F), the cyclization proceeds readily [26].…”

High yield synthesis of 4H‐1,4‐benzothiazine‐1,1‐dioxide derivatives

“…An alternative method reported by Schou started from pyridinium sulfonate salts which were converted into 2-cyanomethylsulfonyl acetanilides: base catalyzed ring closure gave the Soxidized benzothiazinic system [3]. Another recent method involved the microwave assisted cyclization of -phenylsulfonyl enaminoacrylates [9]. In this paper we report a new high yield synthesis of 3-substituted 4H-1,4-benzothiazine-1,1-dioxides: this procedure is characterized by few almost quantitative steps allowing the preparation of the target compounds bearing a free, unsubstituted NH suitable for further functionalization.…”