A. V. Gulevskaya

ONSH: Optimization of Oxidative Alkylamination Reactions through Study of the Reaction Mechanism

Oxidative alkylamination of electron-deficient (hetero)aromatic compounds, via the nucleophilic substitution of hydrogen, is a methodology that has made significant progress since the introduction of AgPy(2)MnO(4) as oxidant. This oxidant generally gives good conversions and yields, whereas the use of KMnO(4) only sometimes works equally well. In order to rationalize this, the reaction mechanism of oxidative alkylamination has been studied. 3-Nitropyridine (1), 1,3-dinitrobenzene (2), and quinazoline (3) were chosen as model substrates and n-butylamine and pyrrolidine as model alkylamines. The rate-limiting step of the mechanism for these substrate/alkylamine combinations was determined. With the use of (1)H NMR spectroscopy thermodynamic properties of sigma(Eta)-adduct formation were deduced and the effect of additives on the adduct formation was investigated. The fundamental insights resulting from these studies led to the identification of a cheap additive (tetrabutylammonium chloride), which in combination with the standard and cheap oxidant KMnO(4) generally gave excellent yields, similar to the ones previously obtained with more expensive AgPy(2)MnO(4).

Nucleophilic Aromatic Substitution of Hydrogen as a Tool for Heterocyclic Ring Annulation

Publisher Summary S N H methodology finds significant use in organic synthesis. A major advantage of this methodology is that it eliminates the necessity of first introducing a good leaving group into an aromatic substrate. Moreover, in classical S N ipso reactions an acid, such as HHal, H 2 SO 4 or HNO 2 is normally liberated that has to be scavenged. However, in S N H processes, a water molecule is typically formed that can contribute to “green chemistry.” This chapter deals with S N H cyclizations. S N H based heterocyclizations allow the synthesis of a great variety of heterocyclic structures differing in ring size, number of heteroatoms and their type, and degree of unsaturation. Various arenes and hetarenes with appropriate electron deficiency can be used as substrates. In context to future prospects, it is observed that a large number of known S N H cyclizations deals with the pyrrole ring closure, therefore search for new substrates, reagents, and cyclization schemes for the annulation of other heterocyclic rings is desirable. It is also important to optimize reaction conditions as many existing transformations do not provide high enough yields.

6,8-Dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione: a novel method of pyrrole-ring annulation to an azine nucleus based on a tandem SNH–SNH process

Abstract 6,8-Dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione has been shown to react with some secondary amines in the presence of an oxidant to produce 6,8-dimethylpyrrolo[2′,3′;3,4]pyridazino[6,5-d]pyrimidine-7,9(6H,8H)-dione derivatives. The reaction represents a new method of pyrrole-ring annulation to an azine nucleus via a tandem SNH–SNH process.

Purines, pyrimidines, and fused systems based on them

Abstract6,8-Dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione reacts with ammonia or primary amines in the presence of an oxidant to give the corresponding 4-amino derivatives. Reactions with secondary amines (dimethylamine, piperidine, or morpholine) proceed with difficulty, resulting in 3-amino derivatives.

Heterocyclization of enediynes promoted by sodium azide: a case of ambiguity of X-ray data and structure revision.

It has been shown that contrary to the literature data the tandem cyclization of (Z)-1-aryl-3-hexen-1,5-diynes promoted by sodium azide results in the formation of the corresponding [1,2,3]triazolo[1,5-a]pyridines, not 1H-benzotriazole derivatives. Apparently, incorrect structure elucidation made by previous investigators originates from misinterpretation of X-ray data. A number of new transformations of this type as well as X-ray and NMR experiments are discussed.

Nucleophilic cyclizations of enediynes as a method for polynuclear heterocycle synthesis

In this review, data on the heterocyclization of enediynes, initiated by attack of an external anionic nucleophile or a nucleophilic group present in the molecule at the C ≡ C bond of the enediyne, are summarized.

Cyclizations of enediynes under the action of electrophiles

Cyclizations of enediynes initiated by the attack of an external electrophile at the C≡C bond have been considered in this review.

Nucleophilic Substitution of Hydrogen Atoms in the Pyridazine Series. (Review)

Information has been generalized on the nucleophilic substitution of hydrogen in monocyclic and condensed pyridazines, pyridazine N-oxides, and pyridazinium cations.

Purins, pyrimidines, and related condensed systems. 22. Synthesis and heterocyclization of 7-alkynyl- and 6,7-dialkynyllumazines

The reaction of 6,7-dichloro-1,3-dimethyllumazine with terminal alkynes under Sonogashira conditions gave 7-alkynyl-6-chloro- and 6,7-dialkynyl-1,3-dimethyllumazines. It was found that the alkynyllumazines readily add primary and secondary alkylamines at the 7-alkynyl group to form stable enamines, hydrolysis of which gives 7-(β-hydroxyvinyl)lumazines. The heterocyclization of 7-(β-aminovinyl)- and 7-(β-hydroxyvinyl)lumazines has been carried out to give pyrrolo-, pyrido-, furo-, and pyranopteridines.

Reactions of oxidative nucleophilic substitution of hydrogen in nitroarenes

The review summarizes information on the reactions of oxidative nucleophilic substitution of hydrogen in nitro derivatives of carboaromatic substrates with N-, C-, O-, and P-nucleophiles.