S. S. Zlotskii

Solvent- and halide-free synthesis of pyridine-2-yl substituted ureas through facile C–H functionalization of pyridine N-oxides

A novel solvent- and halide-free atom-economical synthesis of practically useful pyridine-2-yl substituted ureas utilizes easily accessible or commercially available pyridine N-oxides (PyO) and dialkylcyanamides. The observed C–H functionalization of PyO is suitable for the good-to-high yielding synthesis of a wide range of pyridine-2-yl substituted ureas featuring electron donating and electron withdrawing, sensitive, or even fugitive functional groups at any position of the pyridine ring (63–92%; 19 examples). In the cases of 3-substituted PyO, the C–H functionalization occurs regioselectively providing a route for facile generation of ureas bearing a 5-substituted pyridine-2-yl moiety.

New routes to the preparation of gem-cyclopentenedicarboxylic acid derivatives

A new route was developed to design esters of gem-dicarboxylic acids of cyclopentene series by CH alkylation of diethyl malonate with cis-1,4-dichlorobutene. Diethyl cyclopent-3-ene-1,1-dicarboxylate was reacted with dichlorocarbene. The structures of the isolated compounds were described in detail by 1H, 13C NMR spectroscopy and GC–MS.

Selective functionalization of the primary hydroxy group in triols

A procedure was suggested for preparing functionally substituted 1,2-diols by O-alkylation of hydroxyalkyl-1,3-dioxacyclanes with alkyl halides, followed by acid hydrolysis. The conditions for selective cleavage of the ethers obtained were found. (2,2-Dimethyl-1,3-dioxolan-4-yl)methyl benzoate under the conditions of acid deacetalization undergoes saponification of the ester group.

Cyclopropyl-containing sulfonyl amino acids: Exploring the enantioseparation through chiral ligand-exchange chromatography

In the scope of a broader study focused on glutamate receptors regulators, we have been engaged in synthesis, analysis and pharmacological characterization of rigid analogues of glutamic acid. These compounds exhibited the bioisosteric replacement of the distal carboxylic group with the sulfonic one. Besides the sophisticated synthetic approach, we targeted preparation of a series of cyclopropyl-containing sulfonyl amino acids and development of a chromatographic enantioselective method suitable for distinguishing and quantifying the resulting isomers. Due to chelating ability, the chiral ligand-exchange chromatography (CLEC) was used for diastereo- and enantioseparation of the synthesized compounds. The CLEC-based enantioseparation was achieved by using a chiral mobile phase (CMP) system with N,N-dimethyl-(S)-phenylalanine [(S)-DMP] as the chiral selector. Only one of the investigated enantiomeric pairs was undiscriminated with the employed CLEC–CMP system which, very importantly, produced the simultaneous diastereo- and enantioseparation of two compounds of the series. Furthermore, the large α and RS values computed for three enantiomer pairs could be a good basis for a successful scale-up to a semi-preparative level.

Cyclic acetals in the synthesis of polyoxamacrocycles

A selective one-pot procedure to access 8-, 9-, and 10-membered polyoxacycles bearing ester functions was elaborated. The procedure involved the copper-promoted reactions of cyclic acetals with ethyl 2-diazo-3-oxobutanoate to give the target compounds in yields up to 99%.

Dichlorocarbenation of conjugated diene hydrocarbons

Partial and complete dichlorocarbenation of conjugated diene hydrocarbons in the presence of the phase-transfer catalyst catamine AB has been studied. It has been shown that at the initial stages of the process (conversion of the reactant olefins below 30%), alkenyl-gem-dichlorocyclopropanes are the main products. In the case of complete carbenation, corresponding bicyclic structures are formed. The structures of the resulting stereoisomers have been described in detail using 1H and 13С NMR methods. The relative reactivity of the initial dienes has been determined using a method of competitive kinetics.

Synthesis of tertiary amines containing gem-dichlorocyclopropane and cycloacetal fragments

Reactions of secondary amines containing gem-dichlorocyclopropane and cycloacetal fragments with allyl chloride, trans-1,3-dichloropropene, benzyl chloride, and chloromethyl-gem-dichlorocyclopropane were studied. The corresponding tertiary amines were obtained in 20–85% yield. Microwave radiation stimulates N-alkylation of the secondary amine containing the heterocyclic moiety. The structures of the tertiary amines prepared were studied. The configuration of the double bond in the trans-1,3-dichloropropene derivative is retained.

Products of direct hydroalkoxylation of norbornene with alcohols over H-beta zeolite catalyst

The reaction of direct hydroalkoxylation of norbornene in the presence of H-beta zeolite catalyst has been studied. It has been found that the selectivity for exo-alkoxynorbornanes of the reaction of norbornene with monohydric alcohols (saturated, unsaturated, or aromatic) reaches 98% at a conversion of 78–98% of the unsaturated compound. The reaction of norbornene with diols (ethylene glycol and 2-butene-1,4-diol) in the presence of H-beta zeolite affords mono- and diethers, whose yield and ratio can be controlled by varying reaction parameters.

New method of preparation of alkoxyacetic acids

In this work, we report the results of lowtempera� ture ozonolysis of benzyl and phenyl allyl ethers for the preparation of methyl benzyland phenoxyace� tates. The esters of arylacetic acids were prepared by two methods: in the methanol-methylene chloride system in the presence of alkali at -65°C or in methanol at -78°C followed by the treatment of intermediate per� oxide products with semicarbazide hydrochloride. The ozonolysis of benzyl and phenyl allyl ethers Ia and Ib in the presence of NaOH was found to lead in high yield and selectivity to esters IIa and IIb, respectively. Byproducts formed in small amounts are the corre� sponding alkoxyacetic aldehydes IIIa and IIIb. At the same time, the treatment of primary ozonation prod� ucts (peroxides) with semicarbazide hydrochloride gives a mixture of esters IIa and IIb and acetals IVa and IVb (Table 1).

Synthesis of amino derivatives of 1,3,5-triazines containing hetero- and carbocyclic moieties

Reactions of chloro-sim-triazines with secondary amines containing 1,3-dioxolane and hemdichlorocyclopropane moieties were studied. Structures of amino derivatives of 1,3,5-triazines containing cyclic acetal and cyclopropane moieties were examined.