Thiocoumarins synthesis

A review of Claisen rearrangements in aqueous solution has appeared. The synthesis of natural products utilizing tandem Diels-Alder additions with sigmatropic rearrangement processes has been reviewed, and a brief review of the regioselective synthesis of coumarins, quinolones and thiocoumarins with 3,4-fused pyran or furan ring systems by the Claisen rearrangement has been presented. ... 

And 5-acetylamino-2-mercaptocinnamic acid has been efficiently cyclized yielding 7- and 6-aminothiocoumarin, respectively, by this approach.These have been extensively utilized for the synthesis of other thiocoumarins (see p. 125). 

Apart from the chemistry of the 4-hydroxy derivative (see p. 126) relatively little investigation in this area has been conducted. Thiocoumarin-3-carbonyl compounds have proved to be effective precursors for the synthesis of the pharmaceutically useful 3-(2-benzimidazolyl) derivatives. Thus, on interaction of the 3-carboxamide with o-phenylenediamine or the 3-aldehyde with o-nitroanilines, the above benzimidazoles or their TV-oxides are formed. 

Amino- and 7-aminothiocoumarin have been thoroughly explored as useful precursors to a wide variety of thiocoumarins. Thus, substituents such as Cl, Br, I, SCN, CN, OH, and OMe have been introduced by way of the Sandmeyer reaction. 6-Aminothiocoumarin is brominated in the 5-posi-tion, whereby 5-bromo- or 5,6-dibromothiocoumarin may be made by way of the corresponding diazonium salt, using hypophosphorous acid or cuprous bromide, respectively. Alternatively, 6-acetylaminothiocoumarin may be nitrated in the 5-position and thus 5-nitro-, 5-amino-, 5,6-diamino-, or 6-chloro-5-nitrothiocoumarins can be prepared by classical syntheses. These derivatives are useful intermediates for the synthesis of further fused thiocoumarins (e.g., 23, 24 and 25 ). 

In our attempt to extend the coupling reaction of arenes with alkenes to the coupling with alkynes, as shown in Scheme 4, it was found that the reaction of arenes with ethyl propiolate in TFA (trifluoroacetic acid) gave addition products instead of a coupling product [3]. This addition reaction has been extended to various alkynes and various arenes and also to intramolecular reactions for synthesis of heterocycles such as coumarins, quinolines, and thiocoumarins. 

The intramolecular version of this reaction provides a general method for synthesis of biologically active heterocycles, for example coumarins, quinolinones, and thiocoumarins, as shown in Schemes 7 and 8 [3a, c]. The reaction tolerates a variety of functional groups, for example Br, CHO, etc. 

Benzisothiazoles.—Synthesis. A number of 1,2-benzisothiazole-3-acetic acids (128) have been prepared with the aim of studying their potential activity as plant hormones. They were produced, usually in near-quantitative yields, by the action of hydroxylamine on substituted 4-hydroxy-l-thiocoumarins (127) (c/. ref. 56). 5-Chloro-l,2-benzisothiazole-3-acetic acid proved very potent, possessing an activity about three times that of of heteroauxin. ... 

This reaction also allows the synthesis of other interesting scaffolds with a wide range of biological activities, among them are coumarins and thiocoumarins [64] and their derivatives that display a remarkable array of biochemical and pharmacological actions and are abundant in numerous natural products. 

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