Thiocarboxylic esters

SYNTHESIS OF THIOLS, THIOETHERS, THIOACETALS AND S-ALKYL THIOCARBOXYLIC ESTERS... 

A procedure, which has been used successfully for the synthesis of dialkyl thioethers from thioacetamide has been extended to the preparation of a range of 5-alkyl thiocarboxylic esters [35] (Table 4.20). The intermediate 5-acyl ethaniminium salt (Scheme 4.14) is not stable and is converted directly into the 5-alkyl thioester. The choice of catalyst affects the yield of the thioesters. Thus, 5-n-octyl thiobenzoate... 

TABLE 4.20 S-Alkyl thiocarboxylic esters from thioacetamide ... 

Both Bu3SnH and (Me3Si)3SiH are able to reduce alkyl iodides or bromides but not alcohols. However, in the Barton-McCombie reaction, they reduce certain alcohol derivatives, namely, ones that contain a C=S double bond (e. g., thiocarboxylic esters or thiocarbonic esters). Figure 1.39 shows how the OH group of cholesterol can he removed by means of a Barton-McCombie reaction. The C=S-containing alcohol derivative used there is a xanthate. 

Thioesters of the type RSC(=S)R (a dithiocarboxylic ester) and RSC(C=0)R (a thiocarboxylic ester) can be generated by reaction of carboxylic acids with thiols. 

An acyl transfer agent which can be used for the synthesis of acid anhydrides is obtained from the reaction of an acid chloride with 4-benzylpyridine (equation 24). In this way benzoic acid anhydride and cinnamic acid anhydride were obtained in 72% and 57% yields, respectively. As the intermediate, 1-acyl-4-benzylidene-l,4-dihydropyridines, can be isolated, Ais procedure should be well suited for the preparation of mixed anhydrides. Mixed aromatic and aliphatic anhydrides can be prepared with 2-ben-zoylthio-l-methylpyridinium chloride and salts of carboxylic acids. These reactions are carried out in aqueous solution. Iliey make use of the high reactivity of esters of thiocarboxylic esters towards nucleophiles. The mixed anhydrides of benzoic acid with 3-phenylpropanoic acid, phenoxyacetic acid, isobu-tyric acid, p-toluic acid and cinnamic acid were formed in 82, 79,61,91 and 66% yields, respectively. 

Three different types of thiocarboxylic esters (and also thiolactones) exist the thiol, thioxo- and dithioesters which, according to the lUPAC rules, are named S-alkyl (S-aryl) carbothioates (1), 0-alkyl (0-aryl) carbothioates (2) or alkyl (aryl) carbodithioates (3). Acylation-type reactions were used for the first preparations of thiol carboxylic esters (1) by Tjuttschew (1863), Saytzeff and Lukaschewicz (1868) and Michler (1875). Thioxocarboxylic esters (2) were first obtained via an acylation route by Matsui (1908). On the other hand, alkyl dithiobenzoates (3 R = Ph), which were first mentioned in a patent by Bioch and H6hn (1908), and alkyl alkanedithioates (3 R = Me, Et, PhCH2), first described by Houben and Schultze (1910), were prepared by alkylation of the corresponding metal carbodithioates. 

Table 1 Physical and Spectroscopic Data of Thiocarboxylic Esters...

Thiocarboxylic esters do not play a major role in biochemistry, with the one exception of acetyl-CoA (4 R = Me), the prototype of acyl-CoAs (4), which represent important energy rich intermediates in amino acid, lipid and glucose metabolism. In fact the thiol esters (4) fit in with the scope of this chapter. They are often formed by acylation reactions and themselves react as acylating agents. 

Methyl and S-aryP thiocarboxylic esters can also be prepared directly from carboxylic acids if thiocyanates or chlorothioformates are used instead of thiols (equations 11 and 12). 

Special thiol carboxylic esters (29) were prepared from aroyl halides and arcne thiolates. These 4,4 -disubstituted S-aryl arenecarbothioates might gain importance from a practical point of view, since they exhibit liquid crystal properties and could be useful as components of a display cell. Another thiocarboxylic ester (30), which was obtained from a zinc thiochelate and benzoyl chloride (equation 19), ° might be potentially useful as a precursor for organic conductors. 

The open-chained thioacetamide, on the other hand, yields iminium salts (34) on acylation. Reaction of (34) with alkyl halides and subsequent hydrolysis results in the formation of thiocarboxylic esters (1). This reaction is actually performed in one step under phase transfer catalysis (equation 21). No unpleasant smelling thiols or thiocarboxylic acids are required as educts, the yields are high and a large variety of substituents R and R are possible. ... 

Acid anhydrides in the presence of basic catalysts can be used instead of acyl chlorides in acylation reactions of thiols.Mixed anhydrides of N-protected amino acids and ethyl carbonate yield the corresponding S-f-butyl thiocarboxylic esters, which are useful reagents for peptide syntheses (equation 22). Acylation of thiols with ketenes (equation 23) is a method of long standing. In many cases the yields are nearly quantitative. Functionalities such as acetamino groups or carbon-carbon double bonds in the thiol are not attacked under the mild reaction conditions and optically active thiol esters are obtained without racemization. 3 ... 

Phenyl carboxylates are reactive enough to form thiocarboxylic esters directly with thiols or thiolate anions. This reaction was applied for the preparation of polyhexamethylene thioterephthalates (equation 24). ... 

Claisen (cf. Volume 2, Chapter 3.4) and Dieckmann (,cf. Volume 2, Chapter 3.5) condensation reactions work well with thiocarboxylic esters (equations 33 and 34). ... 

Phenols undergo Friedel-Crafts type reaction with RSCN in the presence of BCI3 to give the ortho-imino products which, upon hydrolysis, give thiocarboxylic esters . 

This ring is formed by treating a 2-chloro(2-acylamino)pyridine with LDA and a thiocarboxylate ester under argon. 

O-Alkyl thiocarboxylates. Exposure of ketene silyl acetals to hydrogen sulfide at -78°C leads to thiocarboxylic esters. Thus an ordinary ester is converted to the thioester in two steps. 

In a second type of synthesis, amidines are the starting materials. They are, for instance, thioacylated by means of thiocarboxylic esters and subsequentely oxidatively cyclized to give the thiadiazole system 2 ... 

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