Thioamides, tautomerism

When PAN-T samples are heated by a gradual increase of temperature, the mercapto groups of the tautomeric form of the thioamide groups, enter into an intramolecular reaction with the nitrile groups in accordance with the following scheme ... 

Thioamides react under mild conditions with conjugated azoalkenes (32) to give thiazolines (33) that exhibit hydrazono hydrazino tautomerism. X-ray diffraction studies on (33) showed the compound existed as the hydrazono tautomer <95S1397>. 

Beets " suggested that the bitterness of oximes is due to oxime-isonitroso tautomerism, a system analogous to the tautomerism of thioamides (see Section II,4,b). 

It is well known that l,3-thiazine-4,6-diones can exist in three tautomeric forms <1960CB671, 1976KGS1042>. Cycloaddition of chlorocarbonyl ketenes with thioamides has been reported to produce only the 4-hydroxy-l,3-thiazin-6-ones, whereas the same reaction with amides gives either 4-hydroxy-1,3-oxazin-6-ones or a mixture of tautomers depending on the substituents on the starting materials <2005ARK(xv)88>. 

Tautomerism is common in pteridine derivatives and the favored tautomers should be represented by the structural formulas. Amino groups exist as such and not in the iminodihydro form whereas the hydroxy and thiol functions 9 located adjacent or para to a ring nitrogen atom prefer the thermodynamically more stable amide (lactam) and thioamide (thioxo) configuration 8 (Scheme 1) . 

UV spectra play a very important role in the characterization of pteridines and in the determination of tautomeric equilibria as well as pKa values. The shape of the spectra, their dependence on the pH and the typical regions of absorbance are characteristic for structurally related pteridine derivatives and are therefore often used for structural assignments and proofs. A comparative study of xanthopterin (4) and isoxanthopterin (5), respectively, with their corresponding 6- and 7-thioxo derivatives indicates that the thioxo function causes a strong bathochromic shift of almost 70 nm in the neutral species (92HCA2317). Other striking features are the increased acidity of the thioamide ionization and the hypsochromic shift of the absorption on anion formation. 

The usual precursor to the thiazolo-fused systems is a cyclic thioamide or its tautomeric form . A convenient approach to the synthesis of bicyclic [5-5] systems, e.g., the tricyclic thiazolium salt 46 and 2,3-dihydroimidazo[2,l-A]thiazol-5-one 48, involves the N,S-dialkylation of appropriate precursors 45 and 47 with 1,2-dihaloalkanes (Scheme 31) <1999JMC2828, 2002EJC777>. 

Ultraviolet spectra have been used extensively in a study of tautomerism in 2-hydroxy- (821, 1081) and 2-mercaptopyrazines (821, 1100) (see Sections VI. 5 and VI1.3, respectively) and both compounds have been shown to exist predominantly in the form (2, X = 0, S). The wavelengths of the first and second absorption maxima of the different species of 2-mercaptopyrazine (neglecting the effect of methyl substitution) follow the sequence, cation > thioamide > anion > thiol... 

Thiazolin-4-one derivative 29 in hydrazino-hydrazono tautomeric equilibrium is synthesized by cyclization of l,2-diaza-l,3-butadiene 27 with aryl thioamide 28. Subsequent hydrolytic removal of the NH-Boc-hydrazo protecting group provided 5-acetyl-4-hydroxythiazole derivative 30a, which undergoes a-bromination to give a-bromomethyl ketone 30b. This bromide is used to prepare polyfunctionalized 4,5 -bithiazol-4 -ol derivatives via the Hantzsch thiazole synthesis <04SL2681>. 

Thiazinyl complexes can be obtained by reaction of 43 with thioisonico-tinamide (Scheme 28) [35]. Treatment of dichloromethane solutions of 43 with stoichiometric amounts of this thioamide, under reflux, affords [Ru(t 5-C5H5) 4,4-diphenyl-2-(p-pyridinyl)-4H-1,3-thiazinium-6-yl (CO)(P Pr3)]BF4 (98). The formation of 98 can be rationalized, formally, as the addition of one of the two NH bonds of the thioamide at the Cp-C. double bond of the allenylidene ligand of 43, followed by the coordination of the sulfur atom to the C atom of the resulting vinylidene. However, it should be taken into account that primary and secondary thioamides have the tautomeric forms shown in Eq. 3 [37]. 

Chemically, the grouping R-CS-N- as been referred to as thioamide, thionamide, thiocarbamide, or if R is N, as it is in thiouracil, PTU, and MMI, it is called a thioureylene. This structure may exist in either the thioketo or thioenol tautomeric forms. 

The cyclization of several thiourea derivatives 122, which were obtained from the reactions of a number of isothiocyanates 123 and thioamides 124, with AS2O3, phenylarsine oxide, and triphenylarsine, afforded the corresponding 1,3,5,2-dithiazarsinine compounds 125 (Scheme 37) <2002PS497>. Tautomerism between the thiourea 122a and imine-thiol 122b forms has been observed by H and NMR. 

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. 

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