Thiocoumarins, reactions

The intramolecular version of this reaction provides a general method for the preparation of biologically active heterocycles such as coumarins, quinolinones, and thiocoumarins (yield, 50-91%) (Equation (48) and Table 2).47,47b The reaction tolerates various functional groups such as Br, GHO, etc. 

Such a coupling reaction when achieved in electrophilic media was shown to be of a general character. Thus, thiocoumarines could be also converted into corresponding TT-donor dimers in one step and in good yields. 

Kaiser and Wulfers reported the first example of a thietane formation reaction involving photolysis of thiobenzophenone with olefins [27]. Since then a large number of systems have been reported. Thiobenzophenone and related compounds, xanthione and related compounds, the a,p-unsaturated thiones such as thiocoumarin, and adamantanethione have been most thoroughly examined. The wavelength dependence of these reactions has been systematically investigated in order to ascertain differences, if any, in the photochemistry of the thione S2 and T states. Scheme 1 shows one example of photocycloaddition of... 

Toda et al. reported that the topotactic and enantioselective photodimerization of coumarin and thiocoumarin takes place in single crystals without significant molecular rearrangements [49]. Molecular motion needs to be called upon to explain the photochemically activated cycloaddition reaction of 2-benzyl-5-benzylidenecyclopentanone. The dimer molecules, once formed, move smoothly in the reactant crystal to form the product crystal [50]. Harris et al. investigated the reactivity of 10-hydroxy-10,9-boroxophenanthrene in the solid state and the mechanism of the solid-state reaction was characterized by both X-ray diffraction and thermal analysis [51]. It was demonstrated that the solution chemistry of 10-hydroxy-10,9-boroxophenanthrene is different from that in the solid state, where it undergoes dimerization and dehydration to form a monohydride derivative. 

Perkin reaction of this aldehyde with phenylacetic acid gives a mixture of the benzothiophene 13 (57%) and the thiocoumarin 14 (40%). ... 

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 ). 

Since photochemical reactions in inclusion compounds have been described in one chapter of the previous book [1], enantioselective (3-lactam formation reactions are summarized in this present chapter as a typical application of the inclusion technique for enantioselective photosynthesis. In addition, as a representative enantioselective single-crystal-to-single-crystal photoreaction, the photodimerization reactions of coumarin and thiocoumarin in their inclusion compound with a chiral host are also described. Furthermore, a host-catalyzed photodimerization reaction of chalcone and 2-pyridone in the solid state is also added to this chapter as a unique example of the application of inclusion techniques to selective photoreaction. 

The steric course of the photodimerization reactions of coumarin (37a) and thiocoumarin (37b) succeeded in being controlled almost perfectly by carrying out the reaction in inclusion complexes using various host compounds. Furthermore, enantioselective dimerization reactions of 37a and 37b were found to proceed through a single-crystal to single-crystal process. 

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. 

Thiocoumarin (127) underwent [2 + 2]-photocycloaddition reactions in better yields than 126. In contrast to coumarin, cis- and trans-fused products are being found, however, for example, in the reaction with 2,3-dimethyl-2-butene, possibly because the thiopyran ring is more flexible than the pyran ring due to the longer C—S bonds. HTproduct is favored with electron donor-substituted olefins [121]. Electron acceptor substitution in 3-position, as in 3-cyano-l-thiocoumarin (128), leads to an improved performance in [2 + 2]-photocycloaddition reactions [122]. 

Irradiation of 1 1 host-guest crystals of coumarin 85a with (/ ,/ )-(— )-6a derived from tartaric acid gave the (— )-antvdtedd-to-head dimer 86a of 96% ee [88]. Enantiospecific photodimerization of thiocoumarin 85b gave optically pure (+ )-anti-head-to-head dimer 86b when the 1 1 complex with R,R)- — )-6b was used. X-ray structure analysis revealed that the distance between the two ethylenic double bonds was short enough (3.59 and 3.42 A for 85a and 3.73 and 3.41 A for 85b) for addition to occur and topochemically [89]. Further, both reactions were found to proceed via a single crystal-to-single crystal transformation. 

The influence of high intensity ultrasound on various reactions of 4-hydroxycoumarin in aqueous conditions has been studied <03S1286>. 4-Hydroxycoumarins and -thiocoumarins undergo an asymmetric Michael addition to a, 3-unsaturated enones in the presence of imidazoline catalysts. High yields and enantioselectivities are observed and the method has been used to prepare kg quantities of enantiopure warfarin (Scheme 24) <03AG(E)4955>. 

A cyclic thiocoumarin derivative was prepared from 4-methoxybenzylidene thiosalicylaldehyde in a novel use of the three C unit of carbon suboxide. 2-[(4-methoxphenylimino)methyl]thiophenol suspended in ether was treated at -10X with ethereal carbon suboxide during 30 mins, and after stirring at 0 C for 2 nours and completion of reaction over 3-4 days the product, thtocoumarin-3-(N-4-methoxyphenyl)amide, was obtained in 51% yield (ref. 125) by way of a postulated lactam. 

Coumarins and thiocoumarins are accessible from the reaction of methyl salicylate or thiosalicylate with anions derived from simple esters <97JHC1159>. 

Upon oxidation of 1-thiocoumarins (319) with selenium dioxide in iVTV-dimethylformamide, ring-contraction occurs, yielding benzo[ ]thio-phen-2-aldehyde in 80% yield. Possible reaction paths are discussed. A related ring-contraction to 2-bromomethylbenzo[A]thiophen occurs when... 

Thiocoumarin reacts with phenylmagnesium bromide to give a mixture of 2-phenyl-A -thiochromene and thioflavone, the latter product being presumed to arise by oxidation of 4-hydroxy-2-phenyl-A -chromene, formed via a thiopyrylium cation. 4-Hydroxythiocoumarin has been acetylated at the 3-position, by treatment with acetic acid and phosphorus oxychloride reactions of the product with amines and with phenylhydrazine have been studied. ... 

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