Nitriles acid thioamides

Methylisothiazole-5-carboxylic acid has also been prepared by alkaline hydrolysis of the 5-nitrile. The 5-acids decarboxylate readily at or near their melting points but otherwise behave normally, forming acid chlorides, esters, amides, hydra-zides, and nitriles. The esters undergo the Claisen condensation to form ]8-ketoesters, and the nitriles form thioamides with hydrogen sulfide in pyridine. An anomalous reaction is the reduction of 5-cyano-... 

Carboxylic acid thioamides from nitriles GN GSNH2... 

Reactions of a silyllithium reagent with carboxylic acid derivatives, including esters, nitriles, acid chlorides, and thioamides, have been extensively investigated by Fleming. He found that the reaction of acid chlorides with 2 equiv. of PhMe2SiLi affords 1,1-disilylalkoxide 80, in... 

When the Neimentowski reaction is carried out under conventional reaction conditions, the yield and purity of the product are significantly affected by the reaction temperature, reaction time, and reagent ratios. As a result, numerous variations and modifications of this reaction have appeared in the literature since its initial discovery over 100 years ago, resulting in improved yields. Variations of the anthranilic acid component inelude the use of o-acylaminobenzamides, ammonium o-acylaminobenzoates, o-aeetamino-benzonitriles, ° methyl anthranilates, acetanthranils, and isatoic anhydrides in place of anthranilic acid. Conditions wherein the amide component has been replaced with either a nitrile, imidate, " thioamide, or amidine have been reported. Reaction conditions including acetic anhydride" and alkaline peroxide were also developed. More recently, reaction conditions under microwave irradiation have been reported.Details regarding these modifications are summarized below. 

Reaction of Anthranilic Acids or Isatoic Anhydrides with Nitriles, Imidates, Thioamides, or Amidines... 

Nitriles from carboxylic acid thioamides CSNHg CN... 

Chloroform-sodium hydroxide benzyltriethylammonium chloride Nitriles from carboxylic acid thioamides s. 29, 456... 

Via intermediates Amidines from nitriles via carboxylic acid thioamides and thioiminoester salts... 

Aromatic thioamides can be prepared as described in the literature by different ways, either by S -> O exchange between the corresponding benzamides and phosphorus pentasulfide in pyridine solution in the presence of triethylamine (65, 646) as strong base, or by action of H2S on the appropriate nitrile with pyridine and triethylamine solvents using the method of Fairfull et al. (34, 374, 503). In this reaction, thioacetamide in acidic medium can also be used as a H2S generator with dimethylform-amide as the solvent (485). 

Several examples exist for the conversion of 5-aminothiazoles into the corresponding thiazolopyrimidines. Shaw and Butler report the formation of aminothiazole thiocarboxyamide 27 from the thioamide 26 and carbon disulphide using Cook and Heilbron s procedure. Methylation of 27 gave carboxythioimidate 28 which then reacted with sodium hydroxide to give amino-nitrile 29, and with formic acid and acetic anhydride to give the thiazolopyrimidine 30. 

Simple isothiazole-4-carboxylic acids have been made from the corresponding nitriles, which are available in turn from the halogeno derivatives, or directly by the olefin route.5-Aminoiso-thiazole-4-esters and -nitriles are readily obtained by the thioamide route. The 4-acids behave normally and form acid chlorides, esters, amides, and hydrazides. In contrast to the 5-series... 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Tiazofurine (142) is an antimetabolite with antineoplastic activity. It preferentially affects leukemic lymphocytes over normal cells due to selective activation by formation of its adenine dinucleotide by transformed cells. Of the syntheses available, one starts by conversion of iniidate 138 to methyl 2,5-anhydroallonothioate (139). Next, condensation with ethyl 2-amino-2-cyanoac-etate leads to the thioamide which undergoes thiol addition to the nitrile function to produce the amminothiazolecarboxyester system of 140 directly. Sodium nitrite in aqueous hypophosphorus acid eliminates the superfluous amino group via the diazonium transformation to give 141. This synthesis of tiazofurine (142) concludes by ester amide exchange in methanolic ammonia [48]. 

The oxidation of thioamides 63 with a wide variety of oxidizing agents is a well-employed method for the synthesis of 3,5-disubstituted-l,2,4-thiadiazoles 64 <1982AHC285>. However, this method is limited mainly to arylthioamides. The most common oxidizing agents tend to be halogens, hydrogen peroxide, dimethyl sulfoxide (DMSO), and nitrous acid. Yields from these reactions are variable and depend on the thioamide, oxidant, and conditions used (Equation 19). By-products such as nitriles and isothiocyanates are usually formed. 

Sandmeyer s valuable isatin synthesis involves the removal of sulphur from diphenylthiourea (I) (p. 169) with basic lead carbonate. Hydrogen cyanide is combined with the reactive diphenylcarbodiimide (II) so obtained, and the nitrile (III) produced is converted by means of hydrogen sulphide into tbe thioamide (IV). Concentrated sulphuric acid brings about ring closure and the product is the a-anil of isatin (V). Then, by hydrolysis with dilute sulphuric acid, aniline is removed ... 

Thioamides are dehydrosulphurated to nitriles, or converted into 1,2,4-thiadiazoles, depending on whether the reactions are performed in non-acidic solvents such as dichloromethane, chloroform and methanol or in acetic acid. 

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