Structures and reactivities of benzo-1,2,3-dithiazolium salts and their selenium analogs

A number of benzo-1,2,3-dithiazolium chlorides (I) and their selenium analogs — benzo-1,2,3-thiaselenazolium, benzo-2,1,3-thiaselenazolium, and benzo-1,2,3-diselenazolium salts — were synthesized. The electronic structures and reactivities of the I cation and salts I–IV are discussed on the basis of a quantum-chemical calculation of cation I and the PMR spectra of salts I–IV. Successive substitution of the sulfur atoms in the I cation by selenium atoms, particularly in the 2 position, substantially increases the degree of transfer of positive charge to the condensed benzene ring. The trend of the nucleophilic reactivities of 6-methoxy derivatives of salts I–IV in the reaction with aromatic amines is the same as the trend of the degree of localization of the positive charge in the 6 position.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 912–916, July, 1978.     

New heterocyclic system — Bis[1,2,3-benzotriazolo[5,6-b;5′,6′-k]]-18-crown-6

It was shown that 1,2,3-triazole derivatives are formed in the reaction of tetra-nitrodibenzo-18-crown-6 with excess hydrazine or ethylhydrazine in DMSO, while the reaction with phenylhydrazine leads to isomeric products of nucleophilic substitution of the nitro group.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 256–257, February, 1988.     

Nucleophilic reactivity of amines with an α-formylglycyl enol-tosylate fragment

The E-enol-tosylate of S-3-benzyl-6-formylpiperazine-2,5-dione reacts with 1°- and 2°-amines to yield its respective 3S-benzyl-6E-endiamine products while a 3°-amine, DABCO, exclusively yields a bis-3,6-ylidenepiperazine-2,5-dione product. These competitive reaction pathways with amine electron donors are shown to arise mechanistically via the same intermediate, or its tautomers, with an H-bond assisted nucleophilic substitution process being operative in the former case and an elimination reaction pathway in the latter instance.     

Synthesis, Properties, and Reactions of 5-Substituted Derivatives of 2,3-Diphenylquinoxaline [1]

Catalytic hydrogenation of 5-nitro-2,3-diphenylquinoxaline led to the corresponding amine which, in turn, afforded products of nucleophilic substitution on reaction with alkoxymethylene derivatives. Thermal cyclization of selected alkoxymethylene derivatives yielded substituted pyridoquinoxalines. The conditions for successful hydrolysis of ester, decarboxylation of the acid, following chlorination of pyridone and reductive removal of the chlorine atom from it to produce parental heterocycle 2,3-diphenyl-pyrido[2,3-f]quinoxaline were found. All of the tested products of the nucleophilic substitution showed no antibacterial activity.     

Synthesis and reactivity of polyfluorinated fluorosulfatocarbinols in the presence of bases

Compounds CF₃CR(OH)CF₂OSO₂F (I) (R=MeO, Ph) were synthesized by the reaction of -(fluorosulfato)pentafluoroacetone with MeOH or C₆H₆/A1Cl₃. In the presence of bases compound (I), depending on the reaction conditions, forms either cyclic sulfates or products of their isomerization — substituted -fluorosulfato-trifluoropropionic acid fluorides which are capable of nucleophilic substitution of FSO₃ groups in reaction with the nucleophiles.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1584–1588, July, 1991.     

Electrophilic and nucleophilic aromatic substitution: Analogous and complementary processes

Analysis of many variants of nucleophilic aromatic substitution of hydrogen proceeding according to an addition—elimination pattern reveals that this is the major reaction pathway, whereas nucleophilic replacement of halogen or another nucleofugal group is the secondary process, i.e.,ipso-substitution. In this respect electrophilic and nucleophilic aromatic substitution can be considered as analogous processes.This account is published in connection awarding Prof. M. Mgkosza the degree ofDoctor Honoris causa by the Russian Academy of Sciences for his investigations in the fields of physical organic chemistry and fine organic synthesis.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3. pp. 531–544, March, 1996.     

Synthesis of heterocyclic systems on the basis of intramolecular nucleophilic substitution of a nitro group (review)

Literature data on reactions involving intramolecular nucleophilic substitution of nitro groups that lead to new five-, six-, and seven-membered heterorings in various di-, tri-, and polycyclic systems are systematized and correlated. The effect of the conformational structures of the reacting molecules and dipolar aprotic solvents on the reaction and the yields of cyclization products is demonstrated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 867–886, July, 1982.     

Synthesis of New Crown Ethers Containing Appended Pyridine, 10-hydroxybenzoquinoline, 8-hydroxyquinoline and 2-amino-1-hydroxybiphenyl Sidearms

Twelve crown ethers containing one or two arms were synthesized. Two methods were used to attach arms to the azacrown ethers. Ligands 4 - 12 were prepared by a nucleophilic substitution of secondary macrocyclic amine functions on RX ( X=bromide or tosylate groups). Ligands 13 - 15 were obtained via a Mannich reaction of secondary macrocyclic amines with 5-chloro-8-hydroxyquinoline or a substituted-phenol. Diaza-18-crown-6 was treated with 2-bromomethyl-9-methyl-1,10-phenanthroline at the same conditions in which 4 - 8 and 10 - 12 were prepared. In this case, the main product was the diazacrown ether containing one arm. Twelve new aza-crown ethers bearing aromatic and aliphatic side arms were prepared by nucleophilic substitution by secondary macrocyclic amine functions on halide or tosylates or via a Mannich reaction of the macrocyclic secondary amines with phenolic compounds. R=derivatives of pyridine, 8-hydroxyquiniline, and 1-hydroxybiphenyl. Crown ether include aza-15-crown-5 diaza-18-crown-6 diazatrithia-15 (and 16)-crown-6 and diaza-21-crown-7     

Purines,pyrimidines and condensed systems based on them. 10. Reactivity of 1,3-dimethyl-6-chlorolumazine with respect to amines: Competition of aminodechlorination and aminodehydrogenation reactions

1,3-Dimethyl-6-chlorolumazine reacts with secondary alkylamines and hydrazine to form 1,3-dimethyl-6-amino(hydrazino) derivatives in good yields. At the same time, 6-chloro-7-amino-1,3-dimethyllumazines are formed by the action of primary amines and liquid ammonia, in addition to the nucleophilic substitution products of chlorine.Article for Communication 9, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1202–1207, September, 1992.     

Synthesis,Properties, and Reactions of 5-Substituted Derivatives of 2,3-Diphenylquinoxaline [1]

Summary. Catalytic hydrogenation of 5-nitro-2,3-diphenylquinoxaline led to the corresponding amine which, in turn, afforded products of nucleophilic substitution on reaction with alkoxymethylene derivatives. Thermal cyclization of selected alkoxymethylene derivatives yielded substituted pyridoquinoxalines. The conditions for successful hydrolysis of ester, decarboxylation of the acid, following chlorination of pyridone and reductive removal of the chlorine atom from it to produce parental heterocycle 2,3-diphenyl-pyrido[2,3-f]quinoxaline were found. All of the tested products of the nucleophilic substitution showed no antibacterial activity.Dedicated to Prof. Dr. M. Uher on the occasion of his 65^th birthday     

Azaindole derivatives. 62. Synthesis and transformations of condensed three-ring systems that include a 5-azaindoline fragment

The reaction of 7-carbamoyl- and 7-cyano-6-chloro-5-azaindolines with hydrazine leads to the formation of pyrrolo[2,3-d]pyrazolo[5,4-b]pyridine, whereas the reaction of 7-carbamoyl-5-azaindolines with dimethylformamide diethylacetal gives pyrrolo[1,2-c]pyrido]4,3-d]pyrimidines — two new heterocyclic systems. The chemical properties of the synthesized compounds, including cleavage of the pyrimidine ring under the influence of nucleophilic agents, were studied.See [1] for communication 61.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1370–1373, October, 1982.     

Rationalization of the conflicting effects of hydrogen bond donor solvent on nucleophilic aromatic substitution reactions in non-polar aprotic solvent: reactions of phenyl 2,4,6-trinitrophenyl ether with primary and secondary amines in benzene-methanol mixtures

The kinetics of the reactions of phenyl 2,4,6-trinitrophenyl ether with piperidine and cyclohexylamine respectively were studied at different amine concentrations in benzene. The reaction of cyclohexylamine was not base-catalysed while that of piperidine was catalysed by one molecule of the nucleophilic amine. Addition of small amounts of hydrogen-bond donor solvent, methanol to the benzene medium of the reactions produced different effects—rate diminution followed by rate increase in one and continuous rate diminution in the other. These effects are compared with that of aniline (previously studied) in which a continuous rate increase was observed. The results are rationalized in terms of the effect of amine-solvent interaction on the nucleophilicity of the amines in addition to some other factors operating through cyclic transition states leading to products. It is evident from the rationalization that the idea of ‘dimer nucleophile’ in nucleophilic aromatic substitution reactions is erroneous.     

Vicarious nucleophilic substitution in enamine derivatives of 1-hydroxynaphthalene-2,4-dicarbaldehyde

The reaction of aromatic amines with highly stable Schiff base enamines formed from an alkyl amine and 1-hydroxynaphthalene-2,4-dicarbaldehyde resulted in nucleophilic substitution of the alkyl amine with the aromatic amine in ethyl alcohol at room temperature within 1-2 min. This reactivity, regioselectivity and formation of stable derivatives are due to extra stabilization through extended conjugation in these systems.     

Vicarious nucleophilic substitution reactions in azolopyridazines controlled by methyl substituents

Azolopyridazines, when treated with bromomethyl phenylsulfone in DMSO-t-BuOK at room temperature, yield mainly typical VNS reaction products, while 7-methylazolopyridazines under the same conditions undergo annulation with simultaneous conventional ipso nucleophilic substitution of the chlorine at C6. Consequently, methyl substitution offers a convenient means of controlling the course of VNS carbanion substitution. These competitive reactions illustrate the role of charge distribution and steric hindrance for the course of the nucleophilic substitution, and the methylated azolopyridazines appear to be convenient substrates for highly efficient propose annulation in fused azolopyridazine systems.     

Synthesis of polyfunctionally substituted benzothiazines based on vinylthionahlobenzenes and 2-mercaptoethylamine

Regioselective nucleophilic substitution of the fluorine atoms in positions 2 and 5 of the benzene ring takes place in the reaction of 3,6-bis(vinylthio)-1,2,4,5-tetrafluoro- and 3-vinylthio-6-chloro-1,2,4,5-tetrafluorobenzenes with 2-mercaptoethylamine in isopropyl alcohol-water-dimethylformamide mixture at 40–45°C in the presence of KOH. The products of disubstitution obtained are converted into 1,4-benzothiazines on heating to 100°C in dimethylformamide in the presence of K₂CO₃ as a result of intramolecular substitution.Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, Irkutsk 664033, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 706–709, May, 1998.     

Ambidentate reactivity of 3-azapyrylium systems in nucleophilic attack reactions

It has been shown that recyclization of 4-acylmethyl-3-azapyrylium salts under the influence of primary amines affords 4-(-hydrozystyryl)pyrimidinium salts, which, upon further heating with the amine, are recyclized to form 4-acylaminopyridinium salts. It has been established that nucleophilic attack of 6-acylmethyl-substituted 3-azapyrylium salts in aqueous NaOH solution leads to functionally substituted pyridines. By means of MNDO quantum-chemical calculations with an accounting for solvation effects, in a continuum model, it has been shown that two directions of nucleophilic attack of the azapyrylium ring — at positions 2 and 6 — are equally probable.Rostov State University. Scientific-Research Institute of Physical and Organic Chemistry, Rostov State University, Rostov-on-Don 344010. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 697–700, May, 1994. Original article submitted April 18, 1994.     

Studies on pyran,its analogs,and related compounds

The action of guanidine on esters of chromone-2-carboxylic acids leads to the opening of the pyrone ring and to the formation of hydantoin derivatives — 2-imino-5-(2-hydroxybenzoylmethylene)tetrahydroimidazol-4-ones — in addition to other reaction products.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 7, pp. 874–875, July, 1970.     

α-Branched amines through radical coupling with 2-azaallyl anions,redox active esters and alkenes

α-Branched amines are fundamental building blocks in a variety of natural products and pharmaceuticals. Herein is reported a unique cascade reaction that enables the preparation of α-branched amines bearing aryl or alkyl groups at the β- or γ-positions. The cascade is initiated by reduction of redox active esters to alkyl radicals. The resulting alkyl radicals are trapped by styrene derivatives, leading to benzylic radicals. The persistent 2-azaallyl radicals and benzylic radicals are proposed to undergo a radical–radical coupling leading to functionalized amine products. Evidence is provided that the role of the nickel catalyst is to promote formation of the alkyl radical from the redox active ester and not promote the C–C bond formation. The synthetic method introduced herein tolerates a variety of imines and redox active esters, allowing for efficient construction of amine building blocks.

A mild method for the construction of α-branched amine derivatives is presented. SET processes between the Ni catalyst, redox active esters and 2-azaallyl anions generate azaallyl radicals and alkyl radicals that functionalize the alkenes.     

Ultrasound-promoted aromatic nucleophilic substitution of dichlorobenzene iron(II) complexes

The nucleophilic aromatic substitution under ultrasound irradiation of a dichlorobenzene iron η⁶-complex with various secondary amines is reported. The reaction time at moderate temperatures is considerably shortened (15 min) compared to non sonicated reaction conditions at room temperature (several days) or at solvent refluxing temperature (12-48 h). Controlled mono- or di-substitution was achieved by the tuning of the amine nucleophilicity and the solvent polarity. The method was successfully applied to the synthesis of differently substituted phenylenediamines.     

Synthesis of New Substituted 4-Amino-3,5-dinitropyridine Derivatives

Facile synthetic routes for the preparation of some new 4-amino-3,5-dinitropyridine derivatives have been revealed. Nitration of 2-chloropyridin-4-amine （1） as a starting material, in an unexpected one-step reaction, to give dinitrated derivatives, followed by nucleophilic substitution reactions with sodium azide, potassium fluoride, ammonia, methylamine, and 4-nitroimidazol, respectively, gave substituted 4-amino-3,5-dinitropyridine derivatives. Meanwhile, its azide derivative underwent a ring closure conversion into 7-amino-6-nitro-[1,2,5]oxadiazolo[3,4-b]- pyridine-1-oxide. It is of significance that all of the nucleophilic substitution reactions were carried out under mild conditions.