Thiocarboxylic acids reactions

Third in importance are the S-glucuro-nides formed from aliphatic and aromatic thiols (reaction 12 in Fig. 13.21) and from di-thiocarboxylic acids (reaction 13) such as di-ethyldithiocarbamic acid, a metabolite of dis-ulfiram. As for C-glucuronidation (reaction 14), this reaction has been seen in humans for 1,3-dicarbonyl drugs such as phenylbutazone and sulfinpyrazone (28) (Fig. 13.23). 

The only other thiocarboxylic acid examined thus far in this reaction has been thiobenaoio acid, reported by Nylen and Otoeo1740 to give only a poor yield of /J-bydroxyetbyl thioben2oate on addition t > ethylene oxide. 

In this method, the cyclic peptide is generated through cysteine-perthioester cyclization to afford a Xaa-Cys bond whose thiol is then used for the second ligation step to the core through a thiol addition reaction (Scheme 25).[S71 For the perthioester cyclization, the linear precursor 91 consists of an activated N-terminal Cys(Npys) and a C-terminal thiocarboxylic acid which favors cyclization due to intramolecular mixed disulfide formation between them. 

Studies of metal ion promotion of the reactions of thiocarboxylic acids and anhydrides,363 thioamides368"370 and a variety of other sulfur compounds have been carried out. The interested reader should consult the comprehensive review by Satchell.17... 

The reaction of thioethers with ethyleneirnine in the presence of acid yields sulfonium compounds. The reaction is reversible under alkaline conditions (125). Compounds in which double-bonded sulfur can exist in tautomerism with a form having a free SH group, such as thiourea (126,127), thiocarboxylic acids (128), and thiophosphates (129), react to give aminoalkylated products. The (1 ammoetliyl thiocarboxylate rearranges to give the amide. 

In 1996 we performed a classical U-4CR of primary amines, aldehydes and isocyanides, but instead of using carboxylic acids we employed thiocarboxylic acids [17]. The reaction leads highly chemoselectively to a-aminoacyl thioamides and no trace of a-aminothioacyl amides is found. This finding is not noteworthy per se and... 

Fukuyama [5] obtained the thioester 35 from the reaction of the thiocarboxylic acid anion 34 with the / -lactone compound 17. After acidic deprotection of the Boc group, the thiazoline ring is successfully closed in benzene under Dean-Stark conditions (35 —> 33) in yields between 60 and 80 %. Ehrler [6] and Pattenden [7] choose a more classical way. They close the thiazoline ring by condensation of the aminothiol hydrochloride 5 x HCl with a nitrile. The yields are generally modest (45 and 55 %) except in one case [6]. Installation of the necessary nitrile function hinders its repetitive use, as this procedure causes a considerable loss of material. Heathcock [8] and Ehrler [6 choose the thiol-amide 37 as a key compound. Titanium tetra-... 

The reaction of thiocarboxylic acid amides 573 with carbodiimides affords 1,2,4-ttiazoles... 

The esters of phenothiazine-lO-thiocarboxylic acid undergo a similar thermal decomposition yielding 10-dialkylaminoalkylpheno-thiazines and COS however, they are more stable than their oxygen analogs, and the reaction therefore needs more severe conditions, so that the yields are lower owing to the formation of resinous by-products. ... 

Alternatively, the addition of thiols or thiocarboxylic acids to alkenes can be carried out under base catalysis. For example, the reaction of racemic 4-/m-butoxy-2-cyclopentenone with (—)-10-mercaptoisoborneol occurs in the presence of a catalytic amount of A, M, A 1, /V -tetrameth vl-ethylenediamine. The addition product was, however, a 1 1 mixture of the corresponding diastereomeric sulfides 65. 

Although acylation reactions rank among the best-known methods for the synthesis of thiocarboxylic 5-esters (1), there exist other important and convenient routes, - e.g. the alkylation of thiocarboxylate anions (equation 1) or radical addition of thiocarboxylic acids to carbon-carbon double bonds (equation 2). These methods are not dealt with here (qf. Volume 4, Chapter 1.5). 

Unlike carboxylic esters, open-chained S-alkyl thiocarboxylates cannot be obtained by direct proton-catalyzed esterification. Whereas thiocarboxylic acids react with alcohols to form esters as expected, thiol esters are formed on reaction of carboxylic acids with thiols, but the equilibrium is shifted towards the educts and the reaction is not useful for synthetic purposes. Therefore, activation is necessary and several methods have been developed to meet this requirement. 

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. ... 

By addition of thiols to isonitriles thioformimidates (274 equation 147) are accessible. 2-Methyl-propaneisonitrile inserts into the thietane system to give triiminothiolanes (275 Scheme 42). A related insertion of isonitriles into a C—S bond was observed in the reaction of alkylmercaptocyanoacetic acid esters, labile thioimidates (276) are the products. - The addition of thiocarboxylic acids to isonitriles, giving mixed anhydrides of thioformimidic acids and carboxylic acids has been studied. ... 

Reaction of cyclopropenones with thiocarboxylic acids and 70% perchloric acid in ethanol gave 3,3-bis(acylsulfanyl)cyclopropenes 2 in 44-99% yield. 

Thiocarboxylic acid hydrazides and thiosemicarbazides a) Thiocarboxylic acid hydrazides. The reaction of carbon disulfide... 

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