Igor V. Svitanko

Direct oxidation of alkanoic acids and their amides to γ-lactones by peroxydisulphate-containing systems

The reaction of one-electron oxidation of alkanoic acids (I) and their amides (VI) on treatment with Na2S2O8-containing systems has been studied. As a result of the direct one-pot reaction acids (I) and amides (VI) are converted into γ- and δ-lactones, the reaction being regioselective and leading mainly to γ-lactones in up to 35% yield. The regioselectivity of the oxidative lactonisation depends greatly on the nature of alkyl substituents. The results obtained are presented in terms of a mechanism suggesting the generation of acyloxyl and amidyl radicals from (I) and (VI), respectively, followed by a rearrangement via a 1,5- or 1,6-H shift into the corresponding 3- and 4-carboxy- or -carboxamido-alkyl radicals. The latter undergo oxidative cyclisation to produce γ- and δ-lactones. The system Na2S2O8–NaCl–NaOH converts carboxamides (VI) into amines with loss of one carbon atom as a result of a Hoffmann type rearrangement.

N,O-acylotropy in N-methylpentanehydroxamic acid

Abstract N-Methylpentanehydroxamic acid (N-methyl-N-pentanoylhydroxylamine) 1 rearranges into N-methyl-O-pentanoylhydroxylamine 2 through spontaneous N→O acyl migration.

Stereochemistry of the oxidative lactonization of 2- and 3-methylpentanoic acids in the sodium peroxydisulfate-metal chloride system

Conclusions1.The oxidative lactonization of 2- and 3-methylpentanoic acids in the sodium peroxydisulfate—copper chloride or sodium chloride systems takes place regioselectively at the C4 atom with the formation of 2,4- and 3,4-dimethyl-4-butanolides.2.The oxidative lactonization of 3-methylpentanoic acid in the Na2S2O8-CuCl2 system takes place diastereoselectively and leads to trans- and cis-3,4-dimethyl-4-butanolides in a ratio of 1.6∶1. The diastereoselectivity of the reaction is explained by complex formation between the intermediate acyloxyl radicals and the copper ions.

A two-phase solution procedure using mixtures of algorithms in the structure---property problem

Prediction of the properties of chemical compounds by mathematical methods of pattern recognition is considered. The investigation was carried out by the example of the activity of cell division enzyme inhibitors. An approach based on mixtures of algorithms is used as the method for the construction of recognition models. A two-phase solution procedure for the structure–property problem is analyzed. The local classifier based on the nearest neighbor algorithm and the method of clustering sets is also described. New algorithms for the construction of classifier mixtures are compared. The methods of coordinated prediction of the activity of new compounds are examined. A comparison of mathematical modeling results with molecular design methods based on the coordination of compounds with known structures of therapeutic targets is also presented. An experimental study of the biological activity is conducted.

Reaction of N-hydroxy(alkoxy)amidyl and amidoxy radicals in the sodium peroxydisulfate-copper chloride oxidizing system

Conclusions1.N,O-unsubstituted alkanehydroxamic acids R(CH2)4CONHOH (where R=H or Me) are convered in the Na2S2O8-CuCl2 oxidizing system to γ-lactones and 3-chloroalkanoic acids, respectively, by way of N-hydroxyamidyl radicals R(CH2)4CONHO and amidoxyl radicals R(CH2)4C(O)NHO.2.In the Na2S2O8-CuCl2 oxidizing system O-methylpentanehydroxamic acid is converted to a mixture of γ- and δ-valerolactones, with a significant preponderance of γ-lactone.

Reaction of primary aliphatic amines in oxidation systems containing sodium peroxydisulfate

Conclusions1.Primary aliphatic amines RCH2CH2NH2 are converted by the action of the Na2S2O8-CuCl2 system into nitriles RCH2CN, 2,2-dichloroalkanals RCCl2CHO, acids RCH2COOH, and chloroalkanes RCH2CH2Cl. The formation of 2, 2-dichloroalkanals and chloroalkanes are new reactions of oxidative substitution of the amino group in primary aliphatic amines.2.A mechanism for the reactions has been proposed, including the production of aminyl radicals RCH2-CH2NH and their oxidation into aldimines RCH2CH=NH, predecessors of all the reaction products.

Stereochemistry of oxidative chlorination of cyclohexanecarboxylic acid and its methyl ester in the sodium peroxydisulfate-copper chloride system

Conclusions1.Oxidative chlorination of cyclohexanecarboxylic acid and its methyl ester in the peroxydisulfate-copper chloride system occurs preferentially at C3 and C4 atoms.2.Oxidative chlorination of cyclohexanecarboxylic acid is a stereoselective reaction, and trans-3- and trans-4-chlorocyclohexanecarboxylic acids are predominantly formed.

Reaction of amidyl radicals in sodium peroxydisulfate-metal chloride oxidation systems

Conclusions1.Unsubstituted alkanoic acid amides R(CH2)4CONH2 (R=H or alkyl) convert in Na2S2O8-CuCl2 and Na2S2O8-NaCl oxidation systems via intermediate amidyl radicals R(CH2)4C(O)NH intoγ- and δ-lactones with a considerable predominance ofγ-lactones.2.Monoalkyl amides of alkanoic acids are lactonized to an inappreciable extent by the action of the S2O82−-Cl− system; N,N-diethyl valeramide undergoes oxidative dealkylation into N-alkyl valeramide.3.As the result of an oxidative, Hoffmann type rearrangement in a Na2S2O8-NaCl-NaOH system, unsubstituted alkanoic acid amides convert into amines containing one carbon atom less than the initial amides.