Oxidation by HNO 3 at atmospheric pressure of toluenes with electronegative substituents on the benzene ring was studied. A method enabling the corresponding benzoic acids to be obtained in high yields with minimal wastes was developed. The method could be used in the laboratory and in production of medicines.

Methods for identifying contaminants in Russian-made tramadol hydrochloride substance were developed. Detection of the RS , SR -isomer in tramadol hydrochloride substance was by HPLC with UV detection. Identification of (2 RS )[(dimethylamino)methyl]cyclohexanone was by chromatography in a thin layer of sorbent on Sorbfil F 254 plates. The HPLC method was validated in terms of efficiency, linearity, and reproducibility. Detection sensitivity for contaminants was 0.0001 mg/cm 3 (0.02%).

Разработаны методики определения посторонних примесей в отечественной субстанции трамадола гидрохлорида. Для обнаружения RS,SR-изомера в субстанции трамадола гидрохлорида предложен метод ВЭЖХ с УФ-детектированием. Для определения примеси (2RS)­[(диметиламино)метил]циклогексанона предложен метод хроматографии в тонком слое сорбента на пластинках «Sorbfil» F254. Проведена валидация методики ВЭЖХ по показателям эффективность, линейность и воспроизводимость. Чувствительность обнаружения примеси составила 0,0001 мг/см3 (0,02 %).

Изучено окисление толуолов с электроотрицательными заместителями в бензольном кольце азотной кислотой при атмосферном давлении. Разработан способ, позволяющий получать соответствующие бензойные кислоты с высокими выходами при минимальном количестве отходов. Способ может быть реализован как в лабораторной практике, так и на производстве получения лекарственных препаратов.

Предложен новый способ получения феназепама. При создании технологии производства феназепама реализованы общие принципы обеспечения качества субстанций лекарственных средств за счет использования условий и схем синтеза, позволяющих получать максимально чистые соединения.

A new means of preparing phenazepam is proposed. The new manufacturing technology for phenazepam implements the general principles for medicinal substance quality by using synthesis conditions and schemes yielding compounds as pure as possible.

Oxidative bromination of o -xylene with liquid bromine or hydrobromic acid in aqueous solution in the presence of an alkali-metal bromate as the oxidizing agent was studied. The proposed method allowed the amount of wastes to be reduced while maintaining a high yield of bromo- o -xylene, which is used in the synthesis of vitamin B 2 .

Изучено окислительное бромирование o-ксилола жидким бромом или бромистоводородной кислотой в водной среде в присутствии бромата щелочного металла, используемого в качестве окислителя. Предлагаемый метод позволяет сократить количество отходов при сохранении высокого выхода бром-o-ксилола, применяемого в синтезе витамина В2.

Разработан простой и удобный в технологическом плане способ получения 1,2,5-триметилпиперидин-4-она — ключевого соединения в синтезе лекарственного препарата промедол.

A simple and technologically convenient method for the preparation of 1,2,5-trimethylpiperidin-4-one, a key compound in the synthesis of the drug Promedol, was developed.

Разработана методика определения 2-эндо-(6-хлорпиридин-3-ил)-7-азабицикло-[2.2.1]гептана (эпибатидин) и 2-эндо-(6-хлорпиридин-3-ил)-7-азабицикло[2.2.1]гептан-7-ола (биомаркер эпибатидина) в плазме крови на уровне 1 ? 10-5 1 ? 10-3 мг/мл. Методика основана на извлечении компонентов из плазмы крови жидкостно-жидкостной экстракцией и газохроматографическом определении с использованием термоионного или масс-спектрального детекторов. С целью снижения предела обнаружения эпибатидина и его биомаркера при использовании масс-спектрометрического детектора в методику включена стадия дериватизации с помощью N,O-бис(триметилсилил)трифторацетамида или 2,3,4,5,6-пентафторбензилбромида.

A method has been developed for the determination of 2-endo(6′-chloropyridin-3′-yl)-7-azabicyclo[2.2.1]heptane (epibatidine) and 2-endo(6′-chloropyridin-3′-yl)-7-azabicyclo[2.2.1]heptane-7-ol (epibatidine biomarker) in blood plasma at a level of 1 × 10−5–1 × 10−3 mg/mL. The method is based on the extraction of components from blood plasma by liquid-liquid extraction followed by gas-chromatographic determination using thermionic or mass spectrometric detectors. To reduce the limit of detection for epibatidine and its biomarker in using the mass-spectrometric detector, a derivatization stage using N,O-bis(trimethylsilyl)trifluoroacetamide or 2,3,4,5,6-pentafluorobenzyl bromide has been included into the procedure.

A preparative method for the synthesis of analgesic epibatidine, which provides its endo - and exo -isomers with 9.9 and 8.8% yields, respectively, is described.

The problem of pain and analgesia is central in contemporary medicine. The leading place among the multitude of analgesic agents is occupied by opioids. However, opioids have significant disadvantages (respiratory inhibition reaching the level of respiratory arrest, rapidly developing tolerance, and psychological dependence). Thus, creation of new non-narcotic analgesics with high analgesic activity, as high as that of opioids, but not inducing physical dependence, is currently an active area of research. There is significant interest in the alkaloid (-)-epibatidine, identified by Daly in extracts of the skin of the Ecuadorian tree frog Epipedobates tricolor [1]. In mouse experiments, this compound had 200 times more analgesic activity than morphine. Analgesia induced by both (-)-epibatidine and its isomers was not countered by the opiate receptor antagonist naloxone. In addition, the new alkaloid was found to be an agonist of neuronal nicotinic acetylcholine receptors (nAChR). More than 100 studies addressing the synthesis and properties of epibatidine have been published. Most of these are addressed in reviews [2 – 4]. 2-(6-Chloropyridin-3-yl)-7-azabicyclo[2.2.1]heptane can exist as two diastereomers (endo and exo), differing in terms of the position of the 6-chloro-3-pyridine fragment relative to the azabicyclo moiety Of all the methods known for the synthesis of epibatidine, we believe that the method with the greatest potential for preparative-scale synthesis is the scheme reported in [5]. This method of preparing epibatidine has a number of advantages, as it uses available reagents and solvents and does not require expensive catalysts; each stage of the synthesis uses reactions which are classical in organic chemistry. In addition, this method can be used to synthesize both the endo and the exo isomers. However, the total yield of exo-epibatidine is no more than 1.5% in terms of 1-nitropentan-4-one (II) [5]. The aim of the present work was to optimize the synthesis conditions for each stage of this scheme. 1-Nitropentan-4-one (II) was prepared using the method described in [6]. However, use of these synthesis conditions gave a yield of 1-nitropentan-4-one (II) of no more than 45%. With the aim of increasing the yield of II, we proposed slow addition of methylvinylketone to the catalyst suspension (KF/Al 2 O 3 ) at a 15 – 20 fold molar excess of nitromethane, ensuring that the temperature of the mixture did not exceed 26 – 38°C. After distillation of the reaction mix, the excess (unreacted) nitromethane is used in the next synthesis, use of recovered nitromethane having no effect on target compound yield. The yield of II was 72 – 77%.

A new commercially applicable method for the synthesis of the myorelaxant 1,3,5-tris-(2′-diethylbenzylammonioethyl)- 1,3,5-triazine-2,4,6-trione tribromide (isocyuronium bromide) is described.

A new commercially applicable method for the synthesis of the myorelaxant 1,3,5-tris-(2-diethylbenzylammonioethyl)-1,3,5-triazine-2,4,6-trione tribromide (isocyuronium bromide) is described.

A new commercially applicable method for the synthesis of a myorelaxant - 1,3,5-tris-(2'-diethylbenzylammonioethyl)- 1,3,5-triazin-2,4,6-trione tribromide (isocyuronium bromide) - is described.

A number of permethrin derivatives having various substituents (Me, Et, Pr, Ph, PhCH2, PhCH2CH2) in position 2 of the cyclopropane ring were synthesized and assayed for insecticidal activity against typhoid flies, rice weevils, and black bean aphid and juvenile hormone activity against flour beetle chrysalises. The examined compounds showed a weak insecticidal activity. Some derivatives were found to exert knockdown effect analogous to that of commercial pyrethroid tetramethrin; however, unlike permethrin, they exhibited pronounced juvenile hormone activity.

The purity of the parent substance of ( E )-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methylnaphth-1-ylmethylamine (terbinafine) is evaluated via TLC identification of the main impurities appearing during its synthesis via alkylation of N-methylnaphth-1-ylmethylamine with 1-chloro-6,6-dimethyl-2-hept-2-en-4-yne The possible formation of impurities including N-methyl-N,N-di(methylnaphth-1-yl)amine, N-methylnaphth-1-ylmethylamine, N-methylnaphth-2-ylmethylamine, ( E )-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methylnaphth-1-ylmethylamine, ( Z )-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methylnaphth-1-ylmethylamine, ( E )-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methylnaphth-2-ylmethylamine, and ( Z )-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methylnaphth-2-ylmethylamine was confirmed by means of countersynthesis.