Aleksander А. Golovanov

Objectives. The work sets out to systematize contemporary data on synthesis methods, chemical phenomena, areas and directions of practical application involving the biological activity of 2,2-dimethyl-4-chloromethyl-1,3-dioxolane and a number of its products. Results. The review of scientific literature sets out the latest data on methods of synthesis, chemical transformations, areas and directions of practical application of 2,2-dimethyl-4-chloromethyl-1,3-dioxolane and some products based on it (bis(2,2-dimethyl-4-methylene1,3-dioxolane) trithiocarbonate, patulolide, rivaroxaban, etc.). Chemical transformations of these compounds are described involving the use of 2,2-dimethyl-4-chloromethyl-1,3-dioxolane in the synthesis of substances that support various biological activities. Conclusions. The presence of two main centers of the chloromethyl group in 2,2-dimethyl-4-chloromethyl-1,3-dioxolane opens the way to a variety of derivatives through nucleophilic substitution and the dioxolane ring. The possibility of mass-producing polyfunctional substances, make this a valuable synthon for valuable transformations in the food industry. 2,2-dimethyl-4-chloromethyl-1,3-dioxolane is widely used in pharmaceutical, agrochemical, and oilfield applications for the targeted synthesis of compounds exhibiting anticancer, antifungal, antimicrobial, and anti-inflammatory activity.

The reactions of unsaturated Meldrum’s acid derivatives with azide ions were studied. The selectivity and reaction pathways were determined for two types of substrates, namely enyne and spirocyclopropane derivatives. The enyne derivative undergoes regioselective Huisgen 1,3-dipolar cycloaddition to form a 1,2,3-triazole, while the trimethylsilyl group remains intact, providing opportunities for subsequent modification of the molecule. In contrast, the spirocyclopropane derivative does not undergo cycloaddition but reacts through nucleophilic opening of the strained three-membered ring to form an organic azide. The structures of all the compounds obtained were confirmed using a combination of spectroscopic methods, including NMR spectroscopy, and elemental analysis. The thermal stability of the synthesized azide was assessed using simultaneous thermogravimetric and differential thermal analysis. The low enthalpy of decomposition indicates that this azide is not an explosive compound. The cytotoxicity of the compounds obtained toward human stromal, lung carcinoma, and melanoma cell lines was evaluated using the MTT assay. The cells remained completely viable at a concentration of 50 μM, indicating the absence of toxic effects under these conditions. A fundamental difference was found between the reactivities of activated unsaturated moieties in Meldrum’s acid derivatives. The developed approaches can be used to obtain new triazole and azide structures of interest as synthons for medicinal chemistry and materials science. The results contribute to the development of methods for selective transformations of highly reactive carbocyclic systems and expand the range of tools available for designing biologically active molecules and functional materials.

The direction of lithium aluminum hydride reduction of oximes, derived from two-ring products of cyclohexanone homocondensation, is determined by the position of the double bond in the oxime: [1,1'-bi(cyclohexane)]-1'-en-2-one oxime gives the corresponding primary amine, and [1,1'-bi(cyclohexylidene)]one oxime gives an aziridine derivative. The reaction pathways of [1,1'-bi(cyclohexane)]-1'-en-2-one oxime with methylmagnesium chloride have been established. Methods for the synthesis of bicyclic amines and aziridine derivatives from oximes have been developed.

A synthetic protocol has been developed for the gram-scale synthesis of 4,4,4-trifluorobut-2-ynal based on the commercially available, environmentally friendly fourth-generation refrigerant HFO-1234yf (2,3,3,3-tetrafluoropropene). The synthesis comprises the three following stages: obtaining 3,3,3-trifluoropropyne, its transformation into 4,4-diethoxy-1,1,1-trifluorobut-2-yne via the Bodroux–Chichibabin reaction, and subsequent hydrolysis of the latter compound, giving the final 4,4,4-trifluorobut-2-ynal. The proposed protocol expands the synthetic potential of CF3-alkynes by providing preparative availability for an original organofluorine substance.

Direct interactions of 1-arylpent-1-en-4-yn-3-ones with 2-hydrazinylbenzo[d]thiazoles lead to the formation of the mixtures of 3-styryl- and 5-styryl-1-(benzo[d]thiazol-2-yl)pyrazoles. Under the same conditions, 1,5-diarylpent-1-en-4-yn-3-ones give 5-aryl-3-arylethynyl-1-(benzo[d]thiazol-2-yl)-4,5-dihydro-1H-pyrazoles. We have described and estimated the highly regioselective one-pot synthetic route to luminescent 5-styrylsubstituted pyrazoles containing thiazole and benzo[d]thiazole fragments on the basis of pent-1-en-4-yn-3-ones (cross-conjugated enynones) and 2-hydrazinylbenzo[d]thiazoles. The synthetic protocol involves a preliminary addition of piperidine via the triple bond of pointed cross-conjugated enynones resulting in 1-(piperidin-1-yl)penta-1,4-dien-3-ones that in turn readily form 5-styryl-1-(benzo[d]thiazol-2-yl)pyrazoles with high regioselectivity in excellent yields. The proposed methodology is applicable to a wide range of 1-mono- and 1,5-disubstituted cross-conjugated enynones and monosubstituted hydrazines containing aryl and benzothiazole substituents. The obtained substances exhibit strong luminescence activity (absolute quantum yield reaches 0.7). Structural and regiochemical aspects of the newly synthesized pyrazoles were confirmed by spectral and analytical data.

Objectives . The work set out to obtain the corresponding cyclohexenyl derivatives of 1,4-dioxaspiro[4.5]decane, 1,5-dioxaspiro[5.5]undecane, and 1,4-dithiaspiro[4.5]decane by condensation of 2-(cyclohexen-1-yl)cyclohexanone (Wallach ketone) with 1,2-, 1,3-diols, and 1,2-ethanedithiol; to determine reaction duration and process temperature at which the maximum possible yield of the target cyclic derivatives of 2-(cyclohexen-1-yl)cyclohexanone is achieved; to evaluate the anticorrosive properties of the obtained acetals in an acidic medium; to carry out dichlorocarbenation using 1,4-dioxaspiro[4.5]decane as an example, and to establish the structure of the obtained isomers. Methods . Target compounds including cyclic acetals were obtained by a classical organic synthesis method involving condensation of 2-(cyclohexen-1-yl)cyclohexanone (Wallach ketone) with 1,2-, 1,3-diols, and 1,2-ethanedithiol. The following analysis methods were used to determine the qualitative and quantitative composition of the reaction masses: gas–liquid chromatography (Crystallux-4000M chromatograph with a flame ionization detector, a 25 m × 0.33 mm capillary column containing 100% polydimethylsiloxane as a stationary phase 0.5 μm), nuclear magnetic resonance spectroscopy (BrukerAM-500 device with operating frequencies of 500 and 125 MHz), and elemental microanalysis (rapid gravimetry method). Chlorine and sulfur were determined by the Schöniger method. Results. Under conditions of thermal heating of Wallach ketone with 1,2-, 1,3-diols, and 1,2-ethanedithiol, 1,4-dioxaspiro[4.5]decane, 1,5-dioxaspiro[5.5]undecane, and 1,4-dithiaspiro[4.5]decane were obtained with a yield of 95%. 5,5-Dimethyldioxane derivative was found to have a moderate inhibitory effect on acid corrosion of carbon steel St20 at a temperature of 60°С. Dichlorocarbenation of 1,4-dioxaspiro[4.5]decane was shown to occur with the formation of a mixture of two diastereomers (ratio is 1 : 2) as evidenced by doubled signals of carbon atoms in the carbon spectrum. Conclusions . 2-(Cyclohexen-1-yl)cyclohexanone 1 condenses with 1,2-, 1,3-diols, and ethanedithiol to form the corresponding spirocyclic derivatives in high yields. It is shown that 1,4-dioxaspiro[4.5]decane undergoes dichlorocarbenation under Mąkosza reaction conditions to form polycyclic gem-dichlorocyclopropane as a mixture of two diastereomers. 7-(Сyclohex-1-en-1-yl)-3,3-dimethyl-1,5- dioxaspiro[5.5]undecane is confirmed to inhibit steel corrosion in acidic media.

Unusual condensation of phenylpropargyl aldehyde with acetylacetone in acetonitrile in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene as a catalyst is described. It proceeds at room temperature with the formation of a racemic mixture of (2S,3S,4S,5S,6S)- and (2R,3R,4R,5R,6R)-3,5-diacetyl-2-methyl-4,6-bis(phenylethynyl)tetrahydro-2H-pyran-2-ylacetate instead of expected 3-(3-phenylprop-2-in-1-ylidene)pentane-2,4-dione. The X-ray diffraction and NMR studies of the molecular and crystal structures of this compound reveals an anometric effect that manifests itself at the axial position of the acetoxy group relative to the six-membered heterocycle.

A procedure has been developed for electrophilic addition of 1,2-, 1,3-, and 1,4-diols to 4-methyli­dene-1,3-dioxolane using trifluoroacetic acid as catalyst. Conditions have been found for the predominant formation of monoadducts in 31–70% yield.

Описана необычная конденсация фенилпропаргилового альдегида с ацетилацетоном в ацетонитриле в присутствии 1,8-диазабицикло[5.4.0]ундец-7-ена в качестве катализатора, которая при комнатной температуре протекает с образованием рацемической смеси (2S,3S,4S,5S,6S)- и (2R,3R,4R,5R,6R)-3,5-диацетил-2-метил-4,6-бис(фенилэтинил)тетрагидро-2H-пиран-2-илацетата вместо ожидаемого 3-(3-фенилпроп-2-ин-1-илиден)пентан-2,4-диона. Исследование молекулярной и кристаллической структуры данного соединения методом РСА и спектроскопии ЯМР позволило выявить аномерный эффект, который проявляется в аксиальном положении ацетоксигруппы относительно шестичленного гетероцикла.

As well as the cross-conjugated enynones, propynylidene derivatives of malonic ester and Meldrum’s acid that contain Me3Si, Et3Si and t-BuMe2Si groups, attach stereoselectively 4-methyl-, 4-methoxy- and 4-chlorothiophenol under conditions of base catalysis. In the process, there are sulfanilic compounds containing buta-1,3-diene and penta-1,4-dien-3-one fragments formed in high yields. In the thiylation products of the enyne derivatives of malonic ester and Meldrum’s acid, Me3Si, Et3Si and t-BuMe2Si groups are retained; desilylation occurs during the thiylation of 5-trialkylsilyl-1-phenylpent-1-en-4-yn-3-ones. There are some certain regularities determined for observed reactions. We also developed stereoselective methods for the S-containing polyunsaturated compounds obtaining.