The study of the three-component interaction between 1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide, heterylcarbaldehydes and active methylene nitriles

D A Lega,V P Chernykh,L A Shemchuk

doi:10.24959/ophcj.16.876

Abstract

Some peculiarities of the three-component interaction of 1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide with active methylene nitriles and heterylcarbaldehydes have been described in this article. It has been found that if malononitrile is used, the products of the three-component reaction are 2-amino-4-heteryl-3-cyano-6-ethyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazine 5,5-dioxides irrespective of the heteryl fragment nature in the initial aldehyde. When using ethyl cyanoacetate (as the active methylene nitrile) in the three-component interaction instead malononitrile the reaction lost its selectivity. In this case, depending on the heterylcarbaldehyde, three different types of products were obtained, namely 2-amino-3-alkoxycarbonyl-4-heteryl-4H-pyranes (for pyridine-3-, pyridine-4-carbaldehydes and furan-2-carbaldehyde), thriethylammonium salt of bis(1-ethyl-1H-2,1-benzothiazin-2,2- dioxo-4-ol-3-yl)(2-thienyl)methane (for thiophen-2-carbaldehyde) or ethyl 2-cyano-3-(1H-indol-3-yl)acrylate (for indol-3-carbaldehyde). Formation of a stable triethylammonium salts was considered as the process competitive with formation of 2-amino-4H-pyranes. It has allowes to propose the modiŸed mechanism of 2-amino-4H-pyranes formation. This mechanism includes the stage of forming triethylammonium salts of bis-adducts. According to this mechanism 2-amino-3-ethoxycarbonyl-4-(2-thienyl)-4H-pyrane without any impurity of bis-adduct could be selectively obtained using the three-component interaction. Triethylammonium salts of bis-adducts were obtained by direct interaction of 1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide with heterylcarbaldehydes in the presence of equimolar amounts of triethylamine. It has been shown that the three-component interaction of 1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide with active methylene nitriles and heterylcarbaldehydes is a more effective tool in order to obtain condensed 2-amino-4-heteryl-4H-pyranes compared to the stepwise approach.

Highlights

ВИВЧЕННЯ ТРИКОМПОНЕНТНОЇ ВЗАЄМОДІЇ ЕТИЛ-1Н-2,1-БЕНЗОТІАЗИН-4(3Н)-ОН 2,2-ДІОКСИДУ З МЕТИЛЕНАКТИВНИМИ НІТРИЛАМИ ТА ГЕТЕРИЛКАРБАЛЬДЕГІДАМИ Д.А.Лега, В.П.Черних, Л.А.Шемчук Ключові слова: 2,1-бензотіазин 2,2-діоксид; гетерилкарбальдегіди; метиленактивні нітрили; 4Н-пірани; трикомпонентна взаємодія; триетиламонієві солі Описані деякі особливості трикомпонентної взаємодії етил-1Н-2,1-бензотіазин-4(3Н)-он 2,2-діоксиду з метиленактивними нітрилами та гетерилкарбальдегідами
As the result of the experiments conducted it has been found that the three-component reaction of 1ethyl-1Н-2,1-benzothiazin-4(3Н)-one 2,2-dioxide (1) with heterylcarbaldehydes (2а-е) and malononitrile (3) leads to formation of the target 2-amino-3-cyano4H-pyranes (4а-е) (Scheme 2, Method А) in high or excellent yields in all cases, except pyridine-2-carbaldehyde (Table 1)
As the result of high reactivity of pyridine-3-carbaldehyde (4а) and pyridine-4-carbaldehyde (4b) the interaction in these cases proceeded in ethanol at the room temperature for 10 min with almost quantitative yields of the target products (4a,b) (Table 1, Method А)

Summary

Introduction

ВИВЧЕННЯ ТРИКОМПОНЕНТНОЇ ВЗАЄМОДІЇ ЕТИЛ-1Н-2,1-БЕНЗОТІАЗИН-4(3Н)-ОН 2,2-ДІОКСИДУ З МЕТИЛЕНАКТИВНИМИ НІТРИЛАМИ ТА ГЕТЕРИЛКАРБАЛЬДЕГІДАМИ Д.А.Лега, В.П.Черних, Л.А.Шемчук Ключові слова: 2,1-бензотіазин 2,2-діоксид; гетерилкарбальдегіди; метиленактивні нітрили; 4Н-пірани; трикомпонентна взаємодія; триетиламонієві солі Описані деякі особливості трикомпонентної взаємодії етил-1Н-2,1-бензотіазин-4(3Н)-он 2,2-діоксиду з метиленактивними нітрилами та гетерилкарбальдегідами. В этом случае в зависимости от природы гетерилкарбальдегида были получены три типа продуктов, а именно 2-амино-3-алкоксикарбонил-4-гетерил-4Н-пираны (для пиридин-3-, пиридин-4-карбальдегидов и фуран-2-карбальдегида), триэтиламмониевая соль бис(1-этил1H-2,1-бензотиазин-2,2-диоксо-4-ол-3-ил)(2-тиенил)метана (для тиофен-2-карбальдегида) или этил2-циано-3-(1H-индол-3-ил)акрилат (для индол-3-карбальдегида). A variety of new compounds are continuously synthesized due to design of novel biologically active substances In this regard, derivatives of benzothiazinone S,S-dioxide occupy a special place since they are very promising compounds for creating new drugs. Derivatives of benzothiazinone S,S-dioxide occupy a special place since they are very promising compounds for creating new drugs This is associated with their fairly wide range of biological activities. The cyclic sulfonamides (sultams) are important therapeutic and chiral agents [9] This group includes derivatives of 2,1-benzothiazine (benzosultams), the important class of heterocyclic compounds, due to the fact that derivatives of this heterocyclic system possess the versatile range of biological activities. Derivatives of 3,4-dihydro-2,1-benzothiazine 2,2-dioxide have proven their effectiveness against heart diseases as the inhibitors of lipogenase (Fig. 2) [10]

Methods

Results

Conclusion