V. V. Alekseev

Ring-chain isomerism (tautomerism) of functionally substituted hydrazones (review)

The known data on the ring-chain tautomerism (isomerism) of hydrazones with functional substitutents in the alkylidene or hydrazine fragment of the molecules are systematized. The structural factors and conditions that determine the reversible conversion of the corresponding linear derivatives to representatives of heterocycles — isoindole, tetrahydrofuran, pyrazole, isoxazole, 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazine, 1,2,4-triazine, 1,3,4-thiadiazine, 1,2,4,5-tetrazine, etc. — are correlated.

Synthesis of pyrazole, 1,3,4-thiadiazole, and 1,2,4-triazole derivatives by condensatoin of 1,3-dioxo compounds with thiosemicarbazide derivatives

The reaction of β-diketones with 2-unsubstituted thiosemicarbazides leads to the formation of the corresponding 1-thiocarbamoyl-5-hydroxy-2-pyrazolines, which readily undergo aromatization to give pyrazoles, while the reaction of benzoylacetaldehyde leads to the formation of the corresponding hydrazone. Acetylacetone 2-methyl- and 2,4-dimethylthiosemicarbazones are inclined to undergo tautomerization and, depending on the conditions, can exist in enehydrazine, hydrazone, 1,2,4-triazoline, and 1,3,4-thiadiazoline forms or mixtures of these forms. Upon heating these substances are converted to mixtures of the 1,3,5-trimethylpyrazole and the corresponding 1,2,4-triazoline-5-thione. The structures of the compounds were studied by means of IR and 1H, 13C, and 15N NMR spectroscopy and mass spectrometry.

Ring-Chain Tautomerism of 3-Unsubstituted Trifluoromethyl-Containing n-Acyl-5-Hydroxy-2-Pyrazolines

Reaction of the hydrazides of aromatic and pyridine-3(4)-carboxylic acids with 4-ethoxy-1,1,1-tri-fluorobut-3-en-2-one leads to the formation of derivatives having a 5-hydroxy-2-pyrazoline structure. In solution in DMSO-d6 they are capable of exhibiting ring-chain equilibrium involving the 5-hydroxy-2-pyrazoline and enehydrazine tautomers. The latter form is represented by a mixture of Z- and E-isomers with a significant preponderance of the latter. The product from the reaction of 4-aminobenzohydrazide with 4-ethoxy-1,1,1-trifluorobut-3-en-2-one in a ratio of 1:2 has a structure containing 5-hydroxy-2-pyrazoline and enamine fragments.

Synthesis of derivatives of 1,2,4-triazin-3-thione and 5-amino-2-acyl-2,3-dihydro-1,3,4-thiadiazolium salts from 1,2-dicarbonyl compounds and 4-substituted thiosemicarbazides

The reactions of methyl- and phenylglyoxal with 2,4-disubstituted thiosemicarbazides and of diacetyl with 4-monosubstituted thiosemicarbazides gave monothiosemicarbazones which were converted in trifluoroacetic acid into previously unknown 5-amino-2-acyl-2,3-dihydro-1,3,4-thiadiazolium salts. Diacetyl monosemithiocarbazones are cyclized to 5-methylene-1,2,4-triazin-3-thiones which are also obtained in the reaction ofdiacetyl with 2,4-disubstituted thiosemicarbazides. In particular cases the monothiosemicarbazones are converted into the corresponding 5-alkoxy-1,2,4-triazin-3-thiones in the presence of alcohols. The 3-thio-1,2,4-triazinium cations are formed from the 5-methylene- and 5-alkoxy derivatives in trifluoroacetic acid.

1,2,4-Trimethyl-1,2,4-triazolidine-3-thiones and 3,4-dimethyl-2-methylimino-1,3,4-thiadiazolidines

The reaction of aldehydes and ketones with 1,2,4-trimethylthiosemicarbazide in chloroform in the presence of CF3COOH gives the corresponding 1,2,4-triazolidine-3-thiones, which in an excess of trifluoroacetic acid irreversibly and quantitatively recyclize to 2-imino-1,3,4-thiadiazolidine derivatives.

RING-RING TAUTOMERISM

The superposition within a single molecule of competing ring-chain tautomeric pairs, the minimum structural requirement of which is the presence of one nucleophilic (OH, NH, SH, etc.) and two electrophilic (C=N, C=O, etc.) centers or the reverse, is a method of constructing ring-ring or ring-chain-ring tautomeric systems. On the basis of the structural characteristics of alkylidene derivatives of thiohydrazides, thiosemicarbazides, thiocarbonohydrazides and amidrazones, bis-hydrazones, bis-oximes, and oximohydrazones of 1,3-dioxo compounds, it has been possible to realize for the first time heterocyclic, tautomeric combinations of pyrazoline—isoxazoline, isoxazoline—1,3,4-thiadiazoline, pyrazoline—1,3,4-thiadiazoline, 1,3,4-thiadiazoline-1,2,4-triazolidene, 1,2,4-triazolidene—1,2,4,5-hexahydrotetrazine, 1,2,4,5-hexahydrotetrazine—tetrahydropyran, tetrahydropyran—1,3,4-thiadiazoline, etc.

2-phenyl-1,3,4-thiadiazol-2-ines

According to data from the1H and13C NMR spectra in nonpolar media and the mass spectra, alkylidene derivatives of thiobenzhydrazide have a 1,3,4-thiadiazol-2-ine structure rather than a thiobenzhydrazone structure. The products of condensation of thiobenzhydrazide with acetone and anisaldehyde in methanol undergo partial isomerization to thiobenzhydrazones. The hydrochlorides of the compounds under discussion are the corresponding 1,3,4-thiadiazolinium salts, in which the proton is coordinated with the N4, atom. The 2-phenyl-5,5-dimethyl-1,3,4-thiadiazol-2-ine anion has a noncyclic thioenolate structure.

Mass-spectrometric identification of the tautomeric forms of bisthiocarbonohydrazones of ketones in the gaseous phase

Electron-impact mass spectrometry was used to identify the 2-hydrazono-1,3,4-thiadiazolidone form and linear tautomeric forms of bisthiocarbonohydrazones of acetone, pinacolone, and acetophenone. For the derivatives para-nitro- and para-methoxyacetophenone in the gaseous phase, a third possible 1,2,4-triazolidine-3-thione tautomer was detected in addition to the other two. Ions characterizing each of the tautomeric forms were found in the mass spectra of bisthiocarbohydrazones of acetophenones.

Ring-chain tautomerism of the thiosemicarbazones of substituted benzaldehydes and acetophenones in acid media

Ring-chain tautomerism between the protonated form of the thiosemicarbazone and the 5-amino-2,3-dihydro-1,3,4-thiadiazolium cation is characteristic for thiosemicarbazones and 4-methylthiosemicarbazones of substituted benzaldehydes and acetophenones in CF3COOH solutions.

Ring-chain tautomerism of 3-alkylthio-1,5-dihydro-1,2,4-triazolium salts

Ring-chain tautomerism in S-alkylisothiosemicarbazonium salts was detected for the first time by PMR and 13C NMR spectroscopy. It was shown that substitution at the nitrogen atoms stabilizes the cyclic 1,5-dihydro-1,2,4-triazolium form. The data from the mass spectra are given.