Isocyanides in the synthesis of nitrogen heterocycles

Isocyanides have long proved themselves to be irreplaceable building blocks in modern organic chemistry. The unique features of the isocyano group make isocyanides particularly useful for the synthesis of a number of important classes of nitrogen heterocycles, such as pyrroles, indoles, and quinolines. Several cocyclizations of isocyanides via zwitterions and radical intermediates as well as transition-metal-catalyzed syntheses of different types of heterocycles have recently been developed. Methods starting from isocyanides often have distinct advantages over alternative approaches to the same heterocycles because of their enhanced convergence, the great simplicity of most of the operations with them, and the great variety of isocyanides readily available for use. Isocyanides have also been used in some enantioselective syntheses of chiral heterocyclic compounds, including natural products as well as precursors thereof.     

RCM-mediated synthesis of trifluoromethyl-containing nitrogen heterocycles

A ring-closing metathesis mediated pathway to trifluoromethyl-containing piperidines is detailed. This involves the development of a synthetic route to a new (trifluoromethyl)allylating reagent via a Diels-Alder/retro-Diels-Alder strategy, its application in the synthesis of a series of trifluormethyl-substituted diolefin precursors for ring-closing metathesis, and eventually the successful cyclization of these precursor molecules into the corresponding functionalized piperidines.     

N-oxides in the quinoxaline series

Acyl derivatives of 2-aminoquinoxaline and their 1-N -oxides, as well as methyl derivatives of some of those compounds, are synthesized. IR spectra of these compounds in the solid state, and UV spectra of their solutions, showed that, with respect to the ability of its 2-acylamino derivatives to tautomerize to the imido form, quinoxaline is close to pyrimidine, and below quinoline and pyridine. With respect to the amideimide tautomerism equilibrium position, N-oxides of 2-acylaminoquinoxalines differ little from acylamides of quinoxaline themselves. The action of benzene sulfochloride on 2-aminoquinoxaline-1-N-oxide in pyridine below 0°leads to deoxidation of the N O group, and introduction of the benzene sulfonyloxy group at position 3 in the quinoxaline ring.For Part VIII see [17].     

Microwave assisted synthesis of triazolobenzoxazepine and triazolobenzoxazocine heterocycles

Intramolecular click chemistry was utilized to effect synthesis of the benzofused, triazole ring systems. The trimethylsilyl group was found to impede the reaction progress, and therefore, conditions employing in situ removal of the TMS group coupled with microwave irradiation give the penultimate targets with good conversion.     

Intramolecular charge transfer processes in a series of styryl derivatives of pyridine and quinoline N-oxides

Intramolecular charge transfer processes in a series of thetrans-isomers of styryl derivatives of pyridines and quinolines, their hydrochlorides and molecular complexes with BF₃ have been studied by electronic and IR spectroscopy. Electron donor groups involved in direct resonance conjugation with the N-oxide group intensify these processes, while electron acceptor nitro groups somewhat weaken them. Protons and BF₃ coordinate to the oxygen of the NO group to form strong 11 complexes, except in the cases of 4-(4-dimethylaminostyryl)quinoline and pyridine N-oxides, in which a second acceptor molecule adds to the amino group.Petrozavodsk State University, Petrozavodsk 185640, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, 1093–1102, August, 1998.     

N-oxides of the quinoxaline series

When di-N-oxides of -hydroxymethyl derivatives of quinoxaline are heated with dimethyl sulfoxide, the oxidation of a CH₂OH group and the reduction of a neighboring NO group takes place. The N-oxides of 2,3-bis(hydroxymethyl)qninoxaline undergo similar redox processes in the presence of alkaline reagents.For part XV, see [5].     

An atom-economic synthesis of nitrogen heterocycles from alkynes

A robust route to 2,4-disubstituted pyrrole heterocycles relying upon a cascade reaction is reported. The reaction benefits from operational simplicity: it is air and moisture tolerant and is performed at ambient temperature. Control over the reaction conditions provides ready access to isopyrroles, 2,3,4-trisubstituted pyrroles, and 3-substituted pyrollidin-2-ones.     

N-oxides of the quinoxaline series

A further study of the chemical behavior of quinoxaline and its -methyl and hydrdxy derivatives and their N-oxides in oxidation reactions and reactions with acetic anhydride has been carried out. The features of these reactions connected with the structure of the reacting N-oxides are discussed.For part XIV, see [10].     

N-oxides of the quinoxaline series

The reaction of quinoxaline N-oxides with benzenesulfonyl chloride and benzoyl chloride is investigated, and its mechanism discussed. The reaction products are investigated.     

N-oxides of the quinoxaline series

The IR spectra of the hydrochlorides of 2-aminoquinoxaline (II) and its N-oxides are discussed and a comparison of them with the spectra of the analogous sales of 2-aminopyridine and its N-oxide is made. On the basis of the results obtained, it may be concluded that II and its 4-N-oxide are protonated at the cyclic atom of nitrogen N₍₁₎ O group.For part XVI, see [1].     

Oxidation with p-(Methoxycarbonyl)perbenzoic acid 2. Oxidation of nitrogen heterocycles to the N-oxides

Conclusions We have examined the oxidation of various nitrogen heterocycles to the N-oxides with p-(methoxycarbonyl)perbenzoic acid.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2337–2339, October, 1978.Part 1 [1].Deceased.     

Sulfonation of pyridine, 3-hydroxypyridine,and their N-oxides

The sulfonation of pyridine derivatives and their N-oxides in fuming sulfuric acid was studied. 3-Hydroxypyridine N-oxide is sulfonated in the 2 position of the pyridine ring. A probable scheme for the substitution is proposed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 813–815, June, 1973.     

Alpha-(N-carbamoyl)alkylcuprate chemistry in the synthesis of nitrogen heterocycles

The conjugate adducts obtained via coupling of alpha-(N-carbamoyl)alkylcuprates with alpha,beta-ynoates, alpha-allenyl esters, or alpha.beta-enoates or enimides undergo N-Boc deprotection and cyclization onto the ester functionality upon treatment with PhOH/TMSCl, catecholboron bromide, or trimethylsilyl triflate. This two-pot sequence provides synthetic routes to 4-alkylidinepyrrolidine-2-ones, 4-alkylidinepyrrolizidin-2-ones, and 4-alkylidineindolizidin-2-ones via allenyl esters; pyrrolin-2-ones, tetrahydropyrrolizin-2-ones, and tetrahydroindolizin-2-ones via alpha/beta-ynoates; pyrrolidin-2-ones, pyrrolizidin-2-ones, and indolizidin-2-ones via alpha,beta-enoates or alpha.beta-enimides. The reluctance of gamma-carbamoyl-alpha,beta-enoates to undergo E/Z isomerization requires the use of (Z)-beta-iodo-alpha,beta-enoates readily prepared by the addition of HI to the alkynyl esters for the efficient preparation of pyrrolinones, tetrahydropyrrolizinones, and tetrahydroindolizinones. Utilization of omega-functionalized alpha,eta-ynoates or beta-iodo-alpha,beta-enoates allows for cyclization onto the omega-functionality providing for a synthetic route to quinolizidines.     

Acid-base equilibria of substituted pyridine N-oxides in methanol

Acid dissociation constants in methanol for eight substituted pyridine N-oxides having a wide range of acid-base properties, [quinoline N-oxide (bi-cyclic amine N-oxide) and pyridine (heterocyclic amine)] have been determined using the potentiometric titration method. A linear correlation between ourmethanol data and aqueous pK _a values from the literature has been found. As in polar aprotic solvents cationic homoconjugation phenomenon has been found to be present for sufficiently basic N-oxides. The tendency of substituted pyridine N-oxides towards cationic homoconjugation in methanol is weaker than in polar aprotic solvents and increases with increasing basicity of N-oxides. It has also been found that, in contrast to polar aprotic solvents, the cationic homoconjugation phenomenon in methanol is much more pronounced for heterocyclic amines than their N-oxides.     

Direct sp3 C-H bond activation adjacent to nitrogen in heterocycles

Activation of sp(3) C-H bonds adjacent to nitrogen in heterocycles is an attractive transformation that is emerging as a practical method in organic synthesis. This tutorial review aims to summarize the key examples of direct functionalization of nitrogen-containing heterocycles via metal-mediated and metal-catalyzed processes, which is meant to serve as a foundation for future investigations into this rapidly developing area of research. The review covers functionalization of N-heterocycles via alpha-lithiation with alkyllithium/diamine complexes, alpha-amino radical formation, metal-catalyzed direct C-H activation, C-H oxidations and oxidative couplings, and metal-catalyzed carbene insertions.     

Nitration of some 3,5-disubstituted pyridine N-oxides

The preparation of 3-chloro-5-methoxypyridine N-oxide and its nitration are reported. Mononitration yields 5-chloro-3-methoxy-2-nitro-pyridine N-oxide while more drastic conditions give 3-chloro-5-methoxy-2,6-dinitropyridine. Removal of various substituents by base hydrolysis is also discussed.     

Catalytic synthesis and reactions of nitrogen heterocycles (Review)

Studies at the Latvian Institute of Organic Synthesis and literature data from 1984–1994 on organic catalysis in the chemistry of N-heterocycles are reviewed. 77 to prospects for further developments in catalytic reactions of N-heterocycles are examined.