Thioamides from amines

Tertiary amines from thioamides. Alkyldichlorocerium reagents (alkyl group being primary) react with imino thioethers, which are formed by treatment of thioamides with MeOTf. 

Thiopyrrolopyrimidines (135) are available directly from thioamide derivatives (134) upon heating with substituted amines (Equation (46)) <84S703>. 

Dihydro-2//-l,3,5-thiadiazines containing a ring carbonyl or thiocarbonyl group are synthesized from reaction of thioamides with phenoxycarbonyl isocyanate, dimerization of thiocarbamoylisothiocyanates, or dimerization of carbamoyl isocyanates. The latter two [4-1-2] cycloaddition reactions complement the tabulated list of dienes and dienophiles presented in Table 2 (Section 9.09.9.2). 3,6-Disubstituted-3,4-dihydro-2//-l,3,5-thiadiazines are synthesized by treatment of N-substituted A, Wbis(l//-l,2,3-benzotriazol-l-ylmethyl)-amines with thioamides and zinc bromide (Section 9.09.9.1.3). 

Prim, amines from carboxylic acid thioamides s. 17, 77 CSNH2 CH2NH2... 

Synthesis of Amines, Amides, Ureas, Thioamides, and Thioureas. The Fukuyama-Mitsunobu reaction is the best method to synthesize secondary amines from primary amines, avoiding formation of undesired tertiary amines and/or the quaternary ammonium salts (eq 1). ... 

Prim, amines from carboxylic acid thioamides... 

The reaction of dichlorocarbene with primary amides, amidines, thioamides, and aldoximes all yield the corresponding nitriles. N,N-Disubstituted ureas likewise yield the corresponding N,N-disubstituted amine nitrile. This reaction amounts to a dehydration in the case of primary amides, aldoximes, and N,N-disubstituted ureas the elements of hydrogen sulfide are lost from thioamides, and HCN from amidines. 

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

Glycoamidines have been readily prepared by a mercury-promoted reaction of the corresponding thioamides with amines.69 TV-Boc protected amidines have been prepared from /V-(Boc) thioamides by treatment with base and mercury(II) chloride (Scheme 34).70... 

The formation of thioamides from amines (methylamine, dimethylamine and morpholine) and dithioester sulphines, prepared from dithio esters and peracids, is thought to proceed via the intermediates shown in equation 102325. 

The reaction of thioaldehydes, generated from phosphonium ylides and sulphur with secondary amines such as dimethylamine, leads to thioamides. If the thioaldehydes possess a a-hydrogen atom enamines are produced (equation 103)326. 

Direct reduction of a peptide bond with diborane 59 or a thioamide bond with several reductive procedures 60 is an alternative route for the production of a reduced peptide bond in a peptide. In some cases the reductive amination does not give satisfactory results. As described earlier, preparation of Boc-Pher )[CH2N]Pro-OH by reductive amination yields two diastereomers (Scheme ll). 57 In this case treatment of Boc-Phe-Pro-OBzl by diborane yielded the reduced pseudodipeptide Boc-Pher )[CH2N]Pro-OBzl without epimerization (Scheme 12). However, in some cases diborane is not entirely selective for the amide bond and can reduce ester functions when they are present. Another procedure is to prepare endothiopeptides directly from protected dipeptides 61-66 followed by their selective reduction. 60 ... 

Amidines have been prepared from other amidines on insoluble supports by nucleophilic displacement of one amine by another (Entry 1, Table 13.18). Polystyrene-bound thioamides can be converted into amidines by treatment with an aliphatic or aromatic amine in the presence of EDC (Entry 2, Table 13.18). Alternatively, resin-... 

Table 13.21) or from amides by treatment with Lawesson s reagent. Thioamides can also be prepared on cross-linked polystyrene by the addition of H2S to nitriles (Entry 5, Table 13.21), by thiocarbamoylation of resin-bound organolithium compounds (Entry 6), or by the acylation of amines with reactive thio acid derivatives (Entry 7, Table 13.21). 

L-Prolinethioamides (39, R = alkyl including chiral alkyl), prepared from proline and amines, are effective in acetone-benzaldehyde reactions.110 Mechanistic studies focused in particular on suppression of non-enantioselective side-reactions, and also on the role of the side-chain of the catalyst acting as hydrogen bond donor, especially as the thioamides (with their more acidic N—H protons) are more catalytic than their amide analogues. 

Various 2-substituted iV-phenyl-6-phenylimino-3,6-dihydro-2//-thiopyran-4-amines, which are available from 6-substitutcd-5,6-dihydro-2//-thiopyran-2-thioncs, thermally rearrange to 5,6-dihydropyridine-2(l//)-thiones. A resonance stabilized thioamide anion is proposed as the intermediate (Scheme 107) <2001T8305>. 

Carbanions from hydrocarbons, nitriles, ketones, esters, TV./V-dialkyl acetamides and thioamides, and mono and dianions from (3-dicarbonyl compounds are some of the most common nucleophiles through which a new C-C bond can be formed. This C-C bond formation is also achieved by reaction with aromatic alkoxides. Among the nitrogen nucleophiles known to react are amide ions to form anilines however, the anions from aromatic amines, pyrroles, diazoles and triazoles, react with aromatic substrates to afford C-arylation. 

Amination of enethiolates has only been recently tackled by Beslin and Marion [136] and Hartke et al. [137]. Silylketene dithioacetals or lithium enethiolates react with azodicarboxylates to yield a-hydrazino-dithioesters, thionoesters or thioamides. Homologous dithioesters, bearing an amino moiety on the f5 position, have been prepared from the reaction of silylketene dithioacetals with an imine in the presence of a Lewis acid [138]. 

In contrast, the reaction of thionoesters bearing a /Tcarbonyl group with primary amines does not lead to thioamides, but instead to a-oxo ami-noketene acetals, arising from elimination of H2S rather than ROH [71]. 

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