Heterocycles thioamides

Heterocyclic thiones have been extensively studied because of their facility to yield coordination complexes. All the ligands contain thione and occasionally thiol (mer-capto) groups directly attached to the carbon atoms of heterocyclic molecules. They have been previously reviewed by Raper in 1985576, and very recently the same author has reviewed28 the copper complexes of heterocyclic thioamides and related ligands. 

Hadjikakou, S.K., Xanthopoulou, M.N., Hadjiliadis, N. and Kubicki, M. (2003) Synthesis, structural characterisation and study of mercury (II) iodide complexes with the heterocyclic thioamides pyridine-2-thione (pytH) and thiazolidine-2-thione (tzdtH). Crystal structures of [Hgl2(pytH)2] and [Hgl2(tzdtH)2]. Can J Anal Sci Spec, 48 (1), 38-45. 

To our knowledge only one example of a heterocyclic thioamide S-oxide has been reported previously (15). This is probably due to their low chemical stability. 

The pressure-tuning Raman spectra of five solid, diiodine heterocyclic thioamide compounds (mbztS)f (mbztS = N-methyl-2-mercaptobenzothiaz-ole) (1) [(mbztS)f]fIfi (2) (pySH)f (pySH = 2-mercaptopyridine) (3) [(pySH)(pyS] [If (4) (thpm)(Ifi or possibly [(thpm)IJ-v[If- (thpm = 2-mercapto-3,4,5,6-tertahydropyrimidine (5) have been measured for pressures up to 50 kbar using a diamond-anvil cell. Compounds 1, 4, and 5 undergo pressure-induced phase transitions at 35, 25, and 32 kbar. 

Corban G. J., Hadjikakou S. K., Hadjiliadis N., et al. Synthesis, structural characterization, and computational studies of novel diiodine adducts with the heterocyclic thioamides Aknethylbenzothiazole-2-thione and benzimidazole-2-thione Implications with the mechanism of action of antithyroid drugs. 

The most widely used method for the preparation of carboxylic acids is ester hydrolysis. The esters are generally prepared by heterocyclization (cf. Chapter II), the most useful and versatile of which is the Hantzsch s synthesis, that is the condensation of an halogenated a- or /3 keto ester with a thioamide (1-20). For example ethyl 4-thiazole carboxylate (3) was prepared by Jones et al. from ethyl a-bromoacetoacetate (1) and thioformamide (2) (1). Hydrolysis of the ester with potassium hydroxide gave the corresponding acid (4) after acidification (Scheme 1). 

A limited series of amide replacements have been examined including thioamides (219) [163], reverse amides (220) [164], heterocycles (221) [164], ethers (222) [165], carbamates (223), (224) [165], ureas (225) [165] and ketones (226) [166] (see Table 6.19). In general, replacement of the amide results in a loss of binding affinity compared to AEA. In some cases, replacement of the amide results in increased stability with regard to hydrolysis by FAAH [164, 165]. 

There is an enormous literature on thiocarbonyl compounds, due in part to the technical and industrial importance of many of them, including thioamides, thioureas, xanthates, dithiocarbamates and so forth. An excellent, and recent, general review is available.107 There are also specialized reviews germane to the present chapter Griffin, Woods, and Klayman2 discussed the use of thioureas in the synthesis of heterocycles the preparation of thiazoles from thioamides is included in a three-part volume on Thiazoles 108 the use of carbon disulfide in the synthesis of trithiones and related heterocycles has been reviewed by Mayer109 and Huisgen110 has reported numerous examples of 1,3-dipolar cycloadditions in which carbon disulfide was used. 

Thioamides and their use in the preparation of the heterocyclic compounds are widely reported in the literature. Also they attract considerable interests in peptide chemistry. Molecular and crystal structures of some thioamide derivatives have been confirmed by X-ray diffraction data.8 10 Lawesson s reagent or phosphorus pentasulfide (P4S10) is actively used for the synthesis of thio-carbonyl compounds. Their preparation methods, reactions, applications in the synthesis of heterocycles and biological effects are mainly described in this section. 

Reports regarding selenoamides and selenoureas are less than the corresponding thioamides, thioureas, amides and ureas because of instability of compounds including selenium atom and their difficulty in the preparation. Recently, preparation methods to overcome some difficulties have been developed. Their reactions, preparation, application to heterocycles or biological assay systems have been actively investigated. 

Novel C-4 thiazole kainoid analogues have been synthesised from kainic acid 43. This was converted into the a-bromoketone 44 in three steps, which reacted with thioamides and thioureas to form thiazole and aminothiazole heterocycles 45. All the synthesised thiazole kainic acid derivatives exhibited strong binding to the kainate receptors <00BMCL309>. 

General procedure for alkylation of amidic and thioamidic heterocyclic systems... 

Subsequent studies on thioamide pyrans with application of the competitive reactions method contribute to our understanding of the mechanisms of heterocyclizations with cyanothioacetamide 114 (89ZOR1331). 2,6-Diaminothiopyrans 115, on heating in benzene, open their thiopyran ring reversibly forming intermediate 116, which can eliminate cyanothioacetamide 114 or malononitrile 27a with formation of UNs 30 or 117, respectively. The direction of the subsequent reaction with... 

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