Mercapto-substituted carboxylic acids

With Sulfur Nucleophiles N-Carboxy-protected aziridine-2-carboxylates react with thiols to give P-mercapto-ot-amino acid derivatives. The reaction is usually catalyzed by BF3 and the yields range from fair to excellent [15, 16, 108-111]. With N-unprotected 3-substituted aziridine-2-carboxylates, the ring-opening with thiols usually takes place with anti stereoselectivity, especially in the case of the C-3 aliphatic substituted substrates. In cases in which C-3 is aromatic, however, the stereoselectivity has been found to be a function of the substitution pattern on the aromatic ring 3-p-methoxy ph eri yl-su bs li In led aziridines 143a (Scheme 3.51) and... 

Types of compounds are arranged according to the following system hydrocarbons and basic heterocycles hydroxy compounds and their ethers mercapto compounds, sulfides, disulfides, sulfoxides and sulfones, sulfenic, sulfinic and sulfonic acids and their derivatives amines, hydroxylamines, hydrazines, hydrazo and azo compounds carbonyl compounds and their functional derivatives carboxylic acids and their functional derivatives and organometallics. In each chapter, halogen, nitroso, nitro, diazo and azido compounds follow the parent compounds as their substitution derivatives. More detail is indicated in the table of contents. In polyfunctional derivatives reduction of a particular function is mentioned in the place of the highest functionality. Reduction of acrylic acid, for example, is described in the chapter on acids rather than functionalized ethylene, and reduction of ethyl acetoacetate is discussed in the chapter on esters rather than in the chapter on ketones. 

It is often very useful to be able to alkylate a readily available chiral a-hetero-substitut-ed carboxylic acid in an enantiospecific manner, as a means of using the chiral center and at the same time building-up the rest of the target carbon skeleton. Such a reaction has been devised by Seebach and coworkers524. In this process a-hydroxy- and a-mercaptocar-boxylic acids were first reacted with pivaldehyde, to produce a 1,3-dioxolanone or 1,3-oxathiolanone. This was followed by reaction with base and alkylation by an alkyl halide and subsequent hydrolysis to regenerate the hydroxyl or mercapto group (equation 70). The product was obtained in greater than 95% ee. Similar reactions with other electrophiles were also successful. 

Pyrazolo[3,4-Z)]pyridines, the 7-chloro-6-fluoro-2,4-dimethylquinoline and its mercapto-thiadiazolyl or oxadiazolyl quinolines 21 were prepared via Diels-Alder reaction conversion of methyl 2-(3-oxo-3-phenylpropenylamino)benzoate into 3-benzoyl-l.S -quinolin-4-one 22 . A mixture of aniline derivatives and malonic ester gave a variety of 3-aryl-4-hydroxyquinolin-2(l//)-ones 23. Condensation of isatins with ketones afforded quinoline-4-carboxylic acids. 2-Aryl-l,2,3,4-tetrahydro-4-quinolinones 22 and carbazolylquinolone were also prepared. The substitution of 2-chloroquinoline gave the 2-substituted quinolines. Basic alumina has catalyzed the C-C bond formation between 2-hydroxy-1,4-naphthoquinone and 2-chloroquinoline derivative to give 21. Reaction of organic halides with 8-hydroxyquinolines gave the respective ethers. The azodye derivatives of 21 were prepared in the absence of solvent. Silica gel catalyzed the formation of 2-ketomethylquinolines from reaction of 2-methylquinolines with acyl chlorides. 

An improved synthesis of 5-substituted 4-amino-3-mercapto-(4H)-1,2,4-triazoles (105) has been reported which involves the reaction of thiocarbohydrazide with carboxylic acids at the melting temperature. The crude triazoles (105) then provided easy access to the 3,6-disubstituted l,2,4-triazolo[3,4-b][l,3,4]thiadiazoles (106) by reaction with carboxylic acids or their acid chlorides <97JHC1255>. 

When five equivalents of lithium metal were employed in the Birch reduction of thiophene-2-carboxylic acid, ring-opened 5-mercapto product and p,Y-unsaturated carboxylic acid were obtained. Upon heating at 150-160°C, dehydration to the corresponding p,Y-unsaturated 5-thiolactone occurred. It is noteworthy that the double bond was in a cis conformation. Substituted thiophene-2-carboxylic acids exhibited similar behavior (Scheme 117). 

Birch reduction of more heavily substituted thiophene carboxylic acid salts proceeded readily to afford the corresponding substituted 2,5-dihydrothiophenes however, the ring-opened by-product (Z)-5-mercapto-3-pentenoic acid was still detectable. Reduction of dilithium 3,4-dimethylthiophene-2,5-dicarboxylate also... 

Cyclic carbonates react with isocyanates in the presence of catalysts to give oxazolidi-nones with elimination of carbon dioxide The catalysts sometimes cause trimerization of the isocyanate. Carbonates derived from a-hydroxy carboxylic-, a-mercapto carboxylic and a-A-substituted amino acids react with isocyanates with elimination of carbon dioxide to give five-membered ring [3+2] adducts. ... 

Condensed 1,3f4-Thiadiazoles. - Triazolof3,4-b][1,3,4Jthiadiazoles and thiadiazolines are prepared by cyclisation of 3-mercapto-4-amino-1,2,3-triazoles with substituted alkyl carboxylic acids or treatment with HCl followed by reflux with aldehydes. Thiazolo[4,3-b]M,3,4Ithiadiazoles (368 R=Me,Ph,H,R =Ar) result from treatment of acyl rhodanines (367) with PCl. Further reactions of the former have been reported. Imidazo [2,3-b][1,3,4]-... 

The methods outlined, of course, are readily applicable to a wide variety of substituted heterocycles like the carboxyl, hydroxy and mercapto derivatives of pyridines, pyridine 1-oxides, pyrroles, etc. The application to amines and to diaza compounds such as pyrimidine, where the two centers are basic, is obvious except that now 23 takes the role of the neutral compound, 21 and 22 the roles of the tautomeric first conjugate bases, and 20 the role of the second conjugate base. Extensions to molecules with more than two acidic or basic centers, such as aminonicotinic acid, pyrimidinecarboxylic acids, etc., are obvious although they tend to become algebraically cumbersome, involving (for three centers) three measurable Kg s, four Ay s, and fifteen ideal dissociation constants (A ), a total of twenty-two constants of which seven are independent. 

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