Transformation of Thioamides

Desulfurization of phosphonylated thioamides has been achieved by nickel boride.71 73 

---

Transformations of thioamides to amides have been achieved in... 

Transformation of the Nitrile Groups of PAN into Amino Groups Thioamidation... 

The above transformation takes place via the catalytic effect of copper (I), which generated the corresponding carbenoid from a-diazo-p-keto esters. These Cu-carbenoides react with the thiocarbonyl group of thioamides, after cyclocondensation to afford 2-aryl-l,3-thiazole-5-carboxylates (Scheme 18).40... 

Thioamides have been transformed into the corresponding nitriles. Treatment of primary thioamides by tellurium tetrachloride or selenium tetrachloride in combination with triethylamine affords nitriles.66 Treatment of primary amides and thioamides with l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) gives nitriles.67 Reactions of thioamides with metal carboxylates in organic solvents enables the selective preparation of nitriles, imides or amides depending on the substitution pattern of the starting material (Scheme 33).68... 

On treatment with phosphorus pentasulfide, 4-amino-5-thio-477-[l,2,4]triazoles 86 are converted into 6-aryl-3-(2-aminophenyl)[l,2,4]triazolo[3,4-4][l,3,4]thiadiazoles 3. This transformation is presumed to involve three steps first, the transformation of the amide into the thioamide second, transfer of the thioaroyl group from the phenylamino side chain to the iV-amino group of the triazole ring and, finally, cyclodehydrosulfurization leading to 3 (Equation 21) <1989LA1055>. 

Thieno[4,3,2-/g]benz[l]azocine 187 is produced in high yield (79MI397) from oxime 186 by Beckman rearrangement in PPA. Transformations of amide and thioamide groups of azocines 187 and 188, lead to derivatives 189-192, as shown in Scheme 52. 

The most common source of imidates is nitriles (c/. Volume 6, Chapter 2.7) and, as these can be directly transformed into thioamides (c/. Section 2.4.3.4), this one-step approach is usually preferred. Moreover, depending on the reaction conditions and the substitution pattern, thiolysis of imidates may give thioesters rather than thioamides (c/. Volume 6, Chapter 2.5). However, some high-yield applications of imidates in thioamide synthesis have been reported and are detailed in equations (27) ° and (28). ... 

Thiolysis of A/-monosubstituted amidines, R C(= NH)HNR, proceeds unselectively giving a mixture of thioamides R C(S)NH2 and R C(S)NHR. However, lV,lV-disubstituted examples (67) can be cleanly transformed into tertiary thioamides (68 equation 31 ). ... 

Photochemical reactions of nitrogen-containing thiocarbonyl compounds ([2 + 2] cycloaddition to alkenes with formation of thietanes, transformations of thioimides to lactams and cyclic amines, cyclizations of thioamides) 03H(59)399. 

Biologically active molecules containing amide bonds suffer usually of pharmacokinetic liability. In order to increase their stability, bioisosteric transformation of the carboxamide have been performed and yielded a lot of successful examples especially in the area of petidomimetic. The isosteric replacements for peptidic bonds have been summarized by Spatola and by Fauchere. " The most used and well-established modihcations are iV-methylation, configuration change (o-conhguration at Ca), formation of a retroamide or an a-azapeptide, use of aminoisobutyric or dehydroamino acids, replacement of the amidic bond by an ester [depsipeptide], ketomethylene, hydroxyethyl-ene or thioamide functional group, carba replacement of the amidic carbonyl, and use of an olefinic double bond (Figure 15.33). 

The thionation of carboxamides with 1 shows some remarkable selectivitiesd the reagent is especially suited for the formation of )V,7V-disubstituted thiocarboxamides. Under similar conditions as described above, the transformations of 2-methyl-7V-phenylpropanamide and benzamide gave the corresponding thioamides in only 27% and 4.5% yields, respectively. This selectivity is somehow complementary compared with that of Lawes-son s reagent. 

It was reported that Bi(N03)3 5H20 is an efficient reagent for the deprotection of thioamides and thioureas. A variety of these compounds are rapidly transformed... 

Iwata et al. also established the direct catalytic asymmetric aldol reaction of thioamides (Scheme 8.39)." Treatment of an aldehyde and thioamide 259 in the presence of the catalyst containing [Cu(MeCN)4]BF4, (7 ,/ )-Ph-BPE, and lithium phenoxide 260 gave (3-hydroxythioamide 261 in good yield with high stereoselectivity. Thioamide features the direct transformation into aldehyde by using a Schwarz reagent (Scheme 8.40)." They converted aldol adduct 261 into (3-siloxyal-dehyde 262, which was further submitted to the direct stereoselective aldol reaction. Both diastereomers 263 and 264 were obtained in good yield. This protocol is effective to synthesize sequential 1,3-polyols. 

Other variants of this reaction involve the use of HCl salts of a volatile secondary amine in the presence of sodium acetate in DMF [434], dimethylammonium di-methylcarbamate [435] or catalysts [436]. Microwave irradiation leads to good yields of thioamide derivatives in short reaction times [437]. Transformations of dialdehydes with secondary diamines in the presence of sulfur can be used for the synthesis of polymers [438]. 

Gyclohexylamine added to a hot aq. soln. of Na-l-phenylazo-2-thiolsulfatoacet-amidonaphthalene, and the mixture boiled 5 min. NS-cyclohexyl-NO-l-phe-nylazo-2-naphthyl(thio6xamide). Y 96%.—Ar. Bunte salts cannot be transformed into thioamides. F. e. and limitations s. B. Milligan and J. M. Swan, Soc. 1959, 2969. 

Treatment of 3-acetyl-4-methylfurazan with sulfur in morpholine resulted in a Willgerodt-Kindler transformation into the corresponding thioamide (Scheme 74). On further treatment with sulfuric acid 3-methylfurazan-4-acetic acid is obtained (96ROC734, 96ZOR766). 

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]. 

---