Subject thioamides

The preparation and reactions of V-thiocarbonyl carbohydrate derivatives, such as sugar isothiocyanates, thioamides, thioureas, thiocarbamates and their conjugates have been the subject of valuable comprehensive as well as specialized accounts, which should be consulted for details.198... 

Katritzky offers a general one-pot alternative approach to polysubstituted pyrroles utilizing disubstituted olefins of which a wider variety is commercially available compared to acetylenes . Thus, thioamides 32 were subjected to Mannich condensation with aldehydes and BtH to yield functionalized thioamides 33 which were then treated with base... 

Recrystallization of thioamides 24f-h gave colorless or slightly yellow prismatic crystals [49]. All three thioamides were subjected to X-ray single crystal analysis, and it was revealed that they prefer the same conformation 24-1 in which a benzyl group was placed close to the thiocarbonyl group, the same as the major isomer in solution. The alkenyl double bonds are perpendicular to the thioamide group, and twist in the range of 87.9° to 100.5°. 

The resulting thioamide 64 is subjected to cyclodehydratization with the PEG supported Burgess reagent 6225 with the sulfur atom instead of the carbonyl group performing the intramolecular attack on the sulfonate group in a similar way to that described above. The conversion of the oxazoline into a thiazoline ring as the final step yields curacin A (1). 

Ireland utilized a sulfide ring contraction process for the ring-forming step of his synthesis of 47 (see Scheme 1.16) The diethyl acetal of 5-hydroxyhexanal (73) was converted to the trichloroethyl carbonate and the acetal hydrolized to produce aldehyde 74 in 86% yield. Addition of the zinc enolate of N,N-dimethylethanethioamide (75) to 74 then afforded an intennediate hydroxy thioamide which was subjected to acylation and reductive carbonate cleavage to yield 76 (53%). Acylation with chloroacetyl chloride was followed by ring closure to give the macrocycle 77 (24%). 

Synthesis from o-isoascorbic acid Syntheses of 2 and its antipode 37 from the commercially available D-isoascorbic acid have been reported by conversion to the enantiomerically pure acetonide lactone 29 on a large scale in 75% yield (Scheme 5). Lactone 29 was treated with amino vinylsilane 30 to give the amide 31 in 82% yield, which was used in two different ways. Mitsunobu conditions were not successful to convert 31 to 32. However, the conversion has been achieved in 88% yield by mesylation and then subjection to intramolecular cyclization. Treatment of 32 with Lawesson s reagent afforded the respective thioamide, which was treated with BFj OEtj followed by direct reduction with LiBEtjH to provide the 2-(ethylthio)pyrrolidine 35. Cyclization of 35 afforded the single stereoisomeric tetrahydroindolizine 36. Catalytic hydrogenation of 36 followed by deprotection provided 2-cp/-lentiginosine (2). 

A facile and efficient synthetic route to densely substituted thiophenes based on base induced cyclization reaction between thioamides derived from morpholine and a-haloketones has been reported. Thus, the thioamides 4 were subjected to treatment with the haloketones 5 (R = H, Ar, Me) under basic conditions to provide the tetrasubstituted thiophenes 6. Likewise, the reaction was also demonstrated to give good yields of thiophenes when the haloketones were replaced with 2-bromo-3-oxobutyric acid derivatives or propargyl bromide <04T6085>. 

Other methods that have been reported include inducing the cyclization reaction by incorporating thioamide groups [491], copolymerized AF-vinylpyrrolidone [492], or vinyl halogen monomers in copolymerized or grafted form [493]. Stabilizers based on maleic acid are also effective [494,495]. Reviews on the subject have been published by Brown [496] and Krcma [497]. 

A variety of amides and thioamides were subjected to similar treatment but in the presence of triethylamine [30] good yields of aliphatic and benzenoid nitriles were obtained (see Table 6.1). A somewhat more complex intermediate was suggested for this reaction ... 

A proposal for the mechanism of the Fukuyama indole synthesis is proposed as shown below. Treatment of the isonitriles 1 with tributyltin hydride and a catalytic amount of AIBN, affords a-stannoimidoyl radical 2, followed by cyclization, to give radical 16. It was found that the substrates bearing radical-stabilizing groups at the P-position gave indoles 3 in excellent yield after tautomerization, and acidic workup. Similarly, when thioamide derivatives such as 2-alkenylthioanilide 18 are subjected to radical-initiating conditions, radical 5 or imidoyl radical species are formed, which then undergo radical cyclization to furnish 2,3-disubstiuted indoles 6. 

The Hantzsch synthesis has been used to prepare a number of natural and synthetic cyclic peptides incorporating thiazoles. Pattenden and coworkers used the Hantzsch thiazole synthesis in their preparation of an N-Boc protected L-proline thiazole based amino acid, which was subsequently used to generate cyclic hexaeptides and octapeptides. Thioamide 165, prepared from commercially available Boc-L-proline, was subjected to Holzapfel s modified conditions to generate the desired thiazole 166 in 61% yield. The biological evaluation of these compounds is currently under investigation. 

The first example of asymmetric thio-Claisen rearrangement based on axial chirality has been described by our group and involves atropisomeric thioanilides bearing an ortbo-tert-butyl group [132]. These axially chiral thioamides were subjected to LDA deprotonation followed by S-allylation with various allyl halides. 

The hydrogen peroxide oxidation of N-(ethoxycarbonyl)pyrrole-2-thio-carboxamide (225) has been the subject of a recent study by Papadopoulos, who found that in basic media (225) is converted into the corresponding amide, whereas in acidic solution the sulphine (271) is formed. The thiocarbonyl group in (272) [the cyclization product obtained by heating (225) in quinoline] behaved similarly. Several examples of the formation of heterocyclic compounds, especially isothiazole derivatives, by oxidative treatment of appropriate thioamides have appeared. The... 

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