Synthesis of heterocycles from arylacetonitriles: Powerful tools for medicinal chemists

Arylacetonitriles are versatile building blocks for the construction of heterocyclic scaffolds in medicinal chemistry. These intermediates are able to engage in a variety of synthetic transformations, giving rise to diverse biologically active structures. This digest focuses on recent applications of this synthetic methodology by drug discovery teams across several disease areas, with an emphasis on different reaction types.     

Local atomic and electronic structure of quantum dots based on Mn- and Co-doped ZnS

Solid solutions of zinc sulfide with manganese and cobalt are synthesized. Based on the analysis of X-ray diffraction profiles the conclusion is drawn about the formation of a hexagonal wurtzite type structure in the synthesized quantum dot (QD) solutions. The average crystallite sizes are 8 nm and 22 nm for the samples with manganese and cobalt respectively. Results of IR and optical spectroscopy are consistent with the powder X-ray diffraction and X-ray fluorescence data. The question about particle aggregation in isopropanol and DMF solutions is considered. The QD structures based on ZnS particles doped with Mn and Co transition metal atoms are modeled. The possibility to apply X-ray absorption near edge structure (XANES) spectroscopy to verify the atomic structure parameters around the positions of doping transition metal atoms in QDs of the ZnS family is shown. Partial densities of ZnS:Mn and ZnS:Co electronic states are calculated.     

Structure of a bimolecular crystal of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane and methoxy-<Emphasis Type="Italic">NNO</Emphasis>-azoxymethane

The crystal structure of the bimolecular crystal of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) and methoxy-NNO-azoxymethane (МАМ) (1:2) is studied. The CL-20 molecules adopt a ζ-conformation. The crystal structure is formed by layers of CL-20 and МАМ molecules, between which there are shortened NO^δ–?N^δ+O contacts of the neighboring CL-20 and МАМ molecules.     

Structure–reactivity relationship in Diels–Alder reactions obtained using the condensed reaction graph approach

By the structural representation of a chemical reaction in the form of a condensed graph a model allowing the prediction of rate constants (logk) of Diels–Alder reactions performed in different solvents and at different temperatures is constructed for the first time. The model demonstrates good agreement between the predicted and experimental logk values: the mean squared error is less than 0.75 log units. Erroneous predictions correspond to reactions in which reagents contain rarely occurring structural fragments. The model is available for users at https://cimm.kpfu.ru/predictor/.     

Mathematical simulation of the formation of liquid products from catalytic cracking gases over a zeolite-containing catalyst modified with Group VI and VIII metals

The kinetics of the formation of liquid products from catalytic cracking gases over a zeolite-containing catalyst in a flow reactor in the temperature range from 260 to 420°C at GHSV = 30–264 h^–1 and an on-stream time of 5–25 s has been investigated. A kinetic model for the process proceeding according to a likely scheme is proposed. The rate constants and activation energies of certain reactions involved in the process have been determined. A mathematical model of the process taking into account the mass and heat balances, as well as hydrodynamic conditions, has been developed. The concentration and temperature fields and the pressure over the catalyst bed height have been calculated. The target product yield on has been plotted as a function of the on-stream time.     

Y-type zeolites for the catalytic oxidative degradation of organic azo dyes in wastewater

Cobalt- and iron-containing catalysts active in the oxidation of organic dyes with hydrogen peroxide have been prepared from granular synthetic NaY and HY zeolites without a binder by ion exchange followed by heat treatment at 350–500°C. It has been demonstrated by X-ray photoelectron spectroscopy that cobalt and iron in these catalysts are in the form of Co²⁺ and Fe³⁺ ions on the support surface. The FeHY and CoNaY catalysts are most effective and stable in the oxidation of the anionic dye carmoisine in weakly acidic and alkaline media.     

The use of 2D diffractometry data for oriented samples in the choice of a unit cell

An approach for the substantiated choice of the indexing procedure of a diffraction pattern is described. The technique is based on a combined use of powder X-ray diffraction data in Bragg–Brentano schemes and 2D GIXD of mainly oriented polycrystalline samples.     

Properties of methylammonium lead iodide perovskite single crystals

The technique for growing CH₃NH₃PbI₃ single crystals from saturated solutions in concentrated hydroiodic acid is improved by introducing a reducing agent (hypophosphorous acid). The structure of perovskite is confirmed by single crystal XRD. By energy dispersive spectroscopy and X-ray photoelectron spectroscopy it is established that the stoichiometry of the grown crystals corresponds to the CH₃NH₃PbI₃ compound. Changes in the photoluminescence intensity during in-air measurements show that the crystals synthesized using the reducing agent are more stable in the external environment with laser exposure than without it.     

A polymer regulator of enzyme activity

The reaction of the amino group of α-chymotrypsin with poly(N,N-diethylacrylamides) bearing terminal carboxyl groups which have the degree of polymerization ranging from 30 to 180 and which possess an LCST of 34–29°C affords polymer derivatives of the enzyme. It is found that, upon an increase in the temperature of the aqueous solution of the resulting derivatives to 40°C, the derivative with a degree of polymerization of 180 precipitates at 34°C, while the derivatives with a degree of polymerization of 30–80 remain in solution. The activity of α-chymotrypsin as a part of the derivatives with a degree of polymerization of 30 does not change with increasing temperature, whereas the activity of the enzyme as a part of the derivatives with degrees of polymerization of 60 and 80 decays almost to zero near the LCST of the initial polymers. Such a change in the enzyme activity is reversible (the activity fully recovers with a decrease in temperature).     

Reaction of <Emphasis Type="Italic">N</Emphasis>-chloroamines with carbanions derived from ethyl acetoacetate and diethyl malonate

Carbanions derived from ethyl 3-oxobutanoate and diethyl malonate reacted with an equimolar amount of N-chloro-N-ethylethanamine, N-chloromorpholine, or N-chloropiperidine to give diethyl 2,3-diacetylbutanedioate and tetraethyl ethane-1,1,2,2-tetracarboxylate in 68–83% yield. The possibility of heterocoupling of ethyl 3-oxobutanoate and diethyl malonate carbanions by the action of N-chloro-N-ethylethanamine and the effect of the molar reactant ratio on the selectivity of oxidative homo- and heterocoupling were studied.