Tadeusz S. Jagodziński

Intramolecular hydrogen bonding of the enol forms of β-ketoamides and β-ketothioamides. Deuterium isotope effects on 13C chemical shifts☆

Abstract Deuterium isotope effects of 13 C chemical shifts are studied in a series of enol and keto forms of β-ketoamides and the corresponding thioamides. In addition, the 2,6-cyclohexanediketo-1-amides and thioamides are studied. The effects of ring size (five- and six-membered rings) on the isotope effects and the tautomeric nature of the systems are also looked into. Rather unusual isotope effects are found for the amides, indicating a tautomeric system of the CONHRCOHNHR type. This is supported by the 17 O chemical shift studies. The isotope effects of the simple amides are compared with those of the tetracyclines and piroxicams. The study of N -phenyl-3-phenyl-3-oxo-propiothioamide at low temperature reveals that this thioamide exists as a mixture of s-cis and s-trans species. The isotope effects and the influence of intramolecular hydrogen bonding in the two species can thus be studied. Thioamides of indan-1,3-diones show tautomeric behaviour, as revealed by very large deuterium isotope effects of both signs. Deuteriation shifts the equilibrium in the direction of the thioamide. Finally, the tendency of a series of β-hydroxy esters, thioesters, anhydrides, amides, thioamides, aldehydes and ketones to become tautomeric is discussed in terms of hydrogen bonding, isotope effects, 2 Δ C(OD), and the nature of the acceptor.

A friedel-crafts synthesis of m-substituted thiophenecarbothioamides

Abstract The reaction of thiophene and 2,5-dimethylthiophene with isothiocyanates in the presence of aluminum chloride in nitromethane gave rise to the formation of the N-substituted carbothioamides of thiophene-2-carboxylic and 2,5-dimethyl-thiophne-5-carboxylic acid, respectively. Under similar conditions, 2-ethylthio-5-methylthiophene was attacked by the reagent at the carbon atom adjacent to the ethylthio group, whereas 2-phenyl-5-methylthiophene yielded a mixture of the 3 and 4-carbothioamides.

Reactions of β-keto thioamides with α,β-unsaturated aldehydes. Synthesis of 6-hydroxypiperidine-2-thiones and 6H-thiopyrans

Mixtures of 3-benzoylated and 3-unsubstituted 6-hydroxypiperidine-2-thione derivatives were formed in the reaction of benzoyl(acetyl) thioacetamides with α,β-unsaturated aldehydes in refluxing ethanol in the presence of catalytic amounts of triethylamine. A mechanism for the debenzoylation was proposed. Derivatives of 6H-thiopyran were obtained when an analogous reaction was carried out in refluxing pyridine. The structures of all compounds were determined with the aid of 1D NMR (1H, 13C, 13C-DEPT-135) and 2D NMR (1H, 1H COSY, 1H, 1H NOESY, 13C, 1H COSY) spectroscopy.

Reactivity and diastereoselectivity of Michael additions of amines to achiral α,β-unsaturated thioamides

Abstract Heterocyclic, aliphatic amines add to acyclic and cyclic α,β-unsaturated thioamides yielding β-amino-functionalized derivatives. In the case of cyclic acceptors, the formation of both kinetic and thermodynamically controlled products is observed. Tailoring of cis or trans products is thus possible. A mechanism for the addition to cyclic acceptors is proposed and evidence presented to support it. Ease of addition is studied in relation to the structure of the acceptors.

Domino Knoevenagel/Michael addition/C-acylation reaction. Synthesis of 1,3-cyclohexane-1,3-diones

The three component reactions of Meldrum’s acid, 1,3-bis-(benzotriazol-1-yl)propan-2-one or 1-benzotriazol-1-ylpropan-2-one and an aldehyde, carried out in DMF at 60 oC gave rise to 2,4-bis-(benzotriazol-1-yl)cyclohexane-1,3-diones or 4-benzotriazol-1-ylcyclohexane-1,3-diones, respectively, in fairly high yields. Unlike similar reactions reported earlier with acetone, the reactions with 1,3-bis-(benzotriazol-1-yl)propan-2-one and 1-benzotriazol-1-ylpropan-2-one proceeded via an intramolecular acylation of the other methyl group of acetone.