From Thioamides

Dimethylaminoethylthiazoles (17) were prepared from thioamides and l-bromo-4-dimethylamino-2-butanone (16), with R, =Me, CH2Ph, (CH2)NHCOPh, and (Ac)2NCH2 (Scheme 9) (337, 392). 

Similarly, 5-thiazole alkanoic acids and their salts are obtained from thioamides and /3-halo -y-keto acids (695). Thus thioarylamides condensed with 3-aroyl-3-bromopropionic acid (88) in isopropanolic solution in the presence of Na COs give first 4-hydroxy-2-aryl-A-2-thiazoline-5-acetic acid intermediates (89), which were dehydrated in toluene with catalytic amounts of p-toluene sulfonic acid to 2,4-diaryl-5-thiazole acetic acid (90) (Scheme 39) (657), with R = H or Me Ar = Ph, o-, m- or p-tolyl, o-, m-, or P-CIC6H4, 0-, m-, or p-MeOC(iH4, P-CF3C6H4, a-thienyl, a-naphthyl (657). 

The use of a reagent bearing a basic center or the addition of a base to the reaction mixture was recognized as necessary to prevent the acid-catalyzed elimination of the elements of water from the intermediates. Since the publication of this work, a number of similar intermediates have been isolated from thioamides and a-halogeno carbonyl compounds (608, 609, 619, 739, 754, 801), and as a result of kinetic studies, the exact mechanism of this reaction has been well established (739, 821). 

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. 

RCN From amide % yield from thioamide From amidine... 

It has also been shown that the disproportionation reaction, with the generation of the ionic componnd from thioamide-iodine complexes, exhibits pressure dependence [2]. A pressnre increase, leads to the ionic iodonium salt (iii) from (ii) (Scheme 13.2). The favouring of [MBZIM) ] [I3] (24a) formation, is also proven by compntational stndies, based on energetic gronnds [6]. 

In contrast to thiomiinchnones, thioisomiinchnones (5) (l,3-thiazolium-4-olates) have received considerable attention over the past three decades, and a rich array of 1,3-dipolar cycloaddition chemistry is described in Section 10.2.5. These heterocycles were initially constructed by Potts (1,53,57) from thioamides and a-halo acid chlorides, an example of which is shown in Scheme 10.17 (58). 

TABLE 5. Stereochemistry of aldol reaction of magnesium enolates derived from thioamides with aldehydes... 

Preparation of thiazole Hantzsch synthesis can be applied to synthesize the thiazole system from thioamides. The reaction involves initial nucleophilic attack by sulphur followed by a cyclocondensation. 

Isothiazole synthesis Isothiazole can be prepared from thioamide in the following way. 

Sulfur Containing Heterocycles from Thioamide Precursors , M. Tisler, in Organic Sulfur Chemistry , ed. R. K. Freidlina and A. E. Skorova (invited lectures presented at the 9th International Symposium), Pergamon, Oxford, 1980, pp. 209-217. 

This section will be divided into a discussion of reactions carried out starting from thioamides, thioureas, substituted thioureas, dithiocarbamic acids and their ammonium salts, and miscellaneous syntheses. 

Epoxy-l,3-dioxepanes are readily converted into ring-opening products by reaction with nucleophiles. Thus, addition of 124 with dianions 123 generated from thioamides 122 and 2 equiv of -butyllithium yielded a mixture of diastereomers 125 and 126, which were separated by column chromatography (Scheme 31) <2005JOC8148>. 

The use of soft metal ions to direct the course of reactions of sulfur compounds has been utilised in the preparation of nitriles from thioamides. The first step involves the alkylation of the thioamide to give the iminothioester, which is then converted to the nitrile on treatment with mercury(n) salts (Fig. 4-41). 

Imidates, generated from secondary amides, are treated with trimethylsilyhnethyl triflate to give an azomethine ylid which reacts with electron-poor alkenes and acetylenes, yielding A2-pyrroline and pyrrole derivatives.54 Similar transformations are conducted from thioamides (vide infra). 

The starting materials are usually thiocarbonyl compounds, and among them thioamides are the most popular. Two routes allow access to S-allylke-tene aminothioacetals from thioamides deprotonation by base followed by S-allylation, or vice versa. 

Thiopyrrolopyrimidines (135) are available directly from thioamide derivatives (134) upon heating with substituted amines (Equation (46)) <84S703>. 

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