Proton Sponge Zwitterions with Positively and Negatively Charged Hydrogen Bonds: Extremely Polar Organic Compounds and Interplay of [NHN]+ and [NHN]- Properties.

Six previously unknown zwitterions with positively and negatively charged [NHN] hydrogen bonds were synthesized by acylation of 4,5-bis(dimethylamino)-1-tosylamino-8-aminonaphthalene with subsequent alkaline treatment of the resulting 8-acylamino derivatives. Using NMR and XRD measurements in conjunction with quantum chemical DFT/PBE1PBE/6-311++G(d,p) calculations, it was shown that the negatively charged [NHN]- bond in such compounds commonly differs from the [NHN]+ bond by significantly lower linearity, higher asymmetry, and moderate to strong paramagnetic shift of the chelated NH proton signal. Among other remarkable findings, the most important are (1) unusually high polarity (µ = 21-26 D) of the obtained zwitterions, (2) sharp difference in structures of the solid 1,8-bis(tosylated) zwitterion (BTZ) grown from MeCN or DMF, and (3) registration for one of the stereoisomers of BTZ with the record short [NHN]- hydrogen bridge (N···N = 2.510 Å) almost reaching the theoretical limit (2.50 Å) for the [NHN]+ hydrogen bond.

Reaction of quinaldine with 4,6-di(tert-butyl)-3-nitro-1,2-benzoquinone. Dependence of the outcome on the reaction conditions and a deeper insight into the mechanism.

Condensation of quinaldine with 4,6-di (tert-butyl)-3-nitro-1,2-benzoquinone results in the formation of 5,7-di (tert-butyl)-2-(quinoline-2-yl)-1,3-tropolone, 5,7-di (tert-butyl)-4-nitro-2-(quinoline-2-yl)-1,3-tropolone, 3,3-dimethyl-2-(5-hydroxy-4-nitro-3-tert-butyl-6-quinoline-2-yl-pyridine-2-yl)butanoic acid, 6-(2,2-dimethylprop-3-yl)-5-tert-butyl-4-nitro-2-(quinoline-2-yl)-pyridine-3-ol, 1,7-di (tert-butyl)-3-(quinoline-2-yl)-2-azabicyclo-[3.3.0]octa-2,7-diene-4,6-dione-N-oxide. The formation of 1,3-tropolone and pyridine-2-yl butanoic acid derivatives proceeds through a ring expansion and 2-azabicyclo [3.3.0]octa-2,7-diene-4,6-dione-N-oxide via the contraction of the o-quinone ring. The structure of the heterocyclic compounds obtained was justified by X-ray diffraction analysis, NMR spectroscopy, IR- and HRMS-spectrometry, and the proposed mechanisms of their formation include the participation of an intermediate product of the expansion reaction of the o-quinone cycle - 5,7-di (tert-butyl)-4-nitro-2-(quinoline-2-yl)-cyclohepta-1,3,5-triene-1,3-diol, which was first isolated preparatively. The DFT/B3LYP/6-311++G** methods were used to determine the thermodynamic stability of tautomeric forms of intermediate products, as well as the relative stability of NH and OH tautomers of 5,7-di (tert-butyl)-2-(quinolin-2-yl)-1,3-tropolone and 5,7-di (tert-butyl)-4-nitro-2-(quinolin-2-yl)-1,3-tropolone.

A Multifield Study on Dimethyl Acetylenedicarboxylate: A Reagent Able to Build a New Cycle on Diaminoimidazoles.

A new effective method for the synthesis of imidazo[1,5-b]pyridazines derivatives (yields = 68-89%) by the interaction of 1,2-diamino-4-phenylimidazole with DMAD, in methanol and in the presence of a catalytic amount of acetic acid, is proposed. The course of reaction has been examined by classical organic methods, HPLC-MS analysis, and quantum-chemical calculations.

Mechanisms of nitric oxide generation in living systems.

In modern chemical and biochemical studies, special attention is paid to molecular systems capable of generating nitric oxide (NO), which is one of the most important signalling molecules in the body and can trigger a whole cascade of reactions. Despite the importance of this molecule, the mechanisms of its formation in living organisms remain a subject of debate. This review combines the most important methods of releasing NO from endogenous and exogenous sources. The history of endogenous NO donors dates back more than 150 years, since the synthesis of nitroglycerin, which remains the standard vasodilator today, even though it is known that it and many other similar compounds lead to the development of a nitrate tolerance. Particular awareness is devoted to the mechanisms of NO formation without the participation of enzymes, since these methods are most important for creating exogenous sources of NO as drugs. The study of NO formation methods is centred on both the creation of new NO donors and understanding the mechanisms of tolerance to them.

Lithium-Promoted Cycloaddition of Indole-2,3-dienolates and Carbon Disulfide as a One-Pot Route to Thiopyrano[4,3-b]indole-3(5H)-thiones.

A new approach for the annulation of a thiopyrane ring to an indole core under mild conditions was developed. Treating 2-methyl-3-acylindoles with lithium diisopropyl amide leads to the elimination of a proton from the 2-methyl group. The lithium indole-2,3-dienolates obtained were found to react with CS2 to give the corresponding thiopyrano[4,3-b]indole-3(5H)-thiones. The mechanism represents a stepwise addition through ion-pair formation, according to PCM/B3LYP/6-311++G**, PBE1PBE/6-311++G**, and MP2//HF/6-311++G** quantum chemical calculations. AIM calculations revealed the essential role of the Li atom at all stages of the process.

From 3-Acyl-2-methylindoles to γ-Carbolines: Li-Promoted Cycloaddition Reaction and Its Quantum Chemical Study.

A one-pot cycloaddition strategy for obtaining γ-carbolines under mild conditions was developed. The reaction represents a new approach to the annulation of a pyridine ring to an indole core. Treating 2-methyl-3-benzoylindoles with lithium diisopropyl amide leads to the elimination of a proton from the 2-methyl group. The organolithium compounds generated were found to react with nitriles. The resulting 4,5-dihydro-1H-pyrido[4,3-b]indol-1-ols undergo spontaneous water elimination to give the corresponding γ-carbolines. The applicability of this reaction for the synthesis of isoquinolines has been shown. For the first time, a lithium atom was found to be part of an eight-centered polycyclic transition state according to a detailed DFT PCM/DFT/B3LYP/6-311++G(d,p) and ab initio PCM/MP2//HF/6-311++G(d,p) quantum chemical study.

Comprehensive study of nitrofuroxanoquinolines. New perspective donors of NO molecules.

The goal of present work is the study of NO releasing mechanisms in nitrofuroxanoquinoline (NFQ) derivatives. Mechanisms of their structural non-rigidity and pathways of NO donation - spontaneous or under the action of sulfanyl radicals or photoirradiation - were considered in details, both experimentally and quantum chemically. Furoxan-containing systems of the discussed type are not capable of spontaneous or photoinduced decomposition under mild conditions, and sulfanyl (radical) induced processes are the most preferable. It was shown that appropriate modification of NFQ through [3 + 2] cycloaddition and subsequent aromatization is a powerful tool to design new prospective donors of NO molecule. Two newly obtained NFQ derivatives were proven to have unusually high NO activity in full accordance with the theoretical model. We hope that these examples will encourage community to seek for new NO active molecules among cycloadducts and modified furoxanes.