Scandium ion-enhanced oxidative dimerization and N-demethylation of N,N-dimethylanilines by a non-heme iron(IV)-oxo complex

Oxidative dimerization of N,N-dimethylaniline (DMA) occurs with a nonheme iron(IV)-oxo complex, [Fe(IV)(O)(N4Py)](2+) (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine), to yield the corresponding dimer, tetramethylbenzidine (TMB), in acetonitrile. The rate of the oxidative dimerization of DMA by [Fe(IV)(O)(N4Py)](2+) is markedly enhanced by the presence of scandium triflate, Sc(OTf)(3) (OTf = CF(3)SO(3)(-)), when TMB is further oxidized to the radical cation (TMB(?+)). In contrast, we have observed the oxidative N-demethylation with para-substituted DMA substrates, since the position of the C-C bond formation to yield the dimer is blocked. The rate of the oxidative N-demethylation of para-substituted DMA by [Fe(IV)(O)(N4Py)](2+) is also markedly enhanced by the presence of Sc(OTf)(3). In the case of para-substituted DMA derivatives with electron-donating substituents, radical cations of DMA derivatives are initially formed by Sc(3+) ion-coupled electron transfer from DMA derivatives to [Fe(IV)(O)(N4Py)](2+), giving demethylated products. Binding of Sc(3+) to [Fe(IV)(O)(N4Py)](2+) enhances the Sc(3+) ion-coupled electron transfer from DMA derivatives to [Fe(IV)(O)(N4Py)](2+), whereas binding of Sc(3+) to DMA derivatives retards the electron-transfer reaction. The complicated kinetics of the Sc(3+) ion-coupled electron transfer from DMA derivatives to [Fe(IV)(O)(N4Py)](2+) are analyzed by competition between binding of Sc(3+) to DMA derivatives and to [Fe(IV)(O)(N4Py)](2+). The binding constants of Sc(3+) to DMA derivatives increase with the increase of the electron-donating ability of the para-substituent. The rate constants of Sc(3+) ion-coupled electron transfer from DMA derivatives to [Fe(IV)(O)(N4Py)](2+), which are estimated from the binding constants of Sc(3+) to DMA derivatives, agree well with those predicted from the driving force dependence of the rate constants of Sc(3+) ion-coupled electron transfer from one-electron reductants to [Fe(IV)(O)(N4Py)](2+). Thus, oxidative dimerization of DMA and N-demethylation of para-substituted DMA derivatives proceed via Sc(3+) ion-coupled electron transfer from DMA derivatives to [Fe(IV)(O)(N4Py)](2+).     

Reaction of difluorocarbene with 2H-azirines: generation and transformations of strained azomethine ylides -- aziriniodifluoromethanides

The reaction of difluorocarbene with azirines affords a new type of azomethine ylides, viz., strained aziriniodifluoromethanides. 1,3-Dipolar cycloadditions of ylides derived from 2-unsubstituted 3-arylazirines to dimethyl acetylenedicarboxylate and aldehydes give derivatives of 2,2-difluoro-1-azabicyclo[3.1.0]hex-3-ene-3,4-dicarboxylic acids and 1,4-oxazin-3(4H)-ones, respectively. Ylides derived from 2-mono- and 2,2-disubstituted azirines undergo isomerization to 2-aza-1,3-diene derivatives. 2,2-Difluoro-1-azabicyclo[3.1.0]hex-3-enes are transformed into 2-fluoropyridine derivatives in high yields and react with amines to give 2,4-diamino-1-azabicyclo[3.1.0]hex-2-ene derivatives.     

Synthesis and crystal structures of ring A modified glycyrrhetinic acid derivatives derived from 2,3-oxirane and 2,3-thiirane intermediates

A general method for the introduction of thiol groups at positions 1, 2, and 3 of glycyrrhetinic acid has been developed starting from a protected 2α,3α-oxido-derivative. Conversion into the corresponding 2β,3β-epithio-derivative was followed by ring-opening leading to either 2- or 3-substituted thio derivatives. Conversely, 3α-configured allylic alcohol intermediates derived from the 2,3-epoxide provided efficient access to both diastereoisomeric 3-thio derivatives as well as 1α-thio derivatives. The stereochemistry of the newly formed stereogenic centers was rigorously proven using X-ray crystallography.     

2-Bromomethyl derivatives of benzofuran and indole and their reactions with some nucleophilic reagents

The corresponding 2-bromomethyl derivatives of benzofuran and indole were obtained by bromination of 2-methyl-3-carbethoxy-5-methoxybenzofuran and 1,2-dimethyl-3-earbethoxy-5-methoxyindole with N-bromosuccinimide. A number of alkyl(aryl)thiomethyl and dialkylaminomethyl derivatives were obtained by reaction of the 2-bromomethyl derivatives with nucleophilic reagents.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 308–311, March, 1973.     

Studies on the chemistry of pharmacologically active heterocycles. Part I. Acid hydrolysis of hydrazino-1,2,4-triazine derivatives

The acid hydrolysis of 3-hydrazino-5,6-disubstituted-1,2,4-triazine, 3,5-dihydrazino-6-substituted-1,2,4-triazine, and 2-hydrazinopyrimidine derivatives was studied. It was found that the reaction proceeded through the formation of 3-keto and 3,5-diketo derivatives of the related 2,3-dihydro, 2,3,4,5-tetrahydro-1,2,4-triazines, and 2-keto derivatives of 1,2-dihydropyrimidines. It was concluded from these reactions that in 1,2,4-triazine derivatives the C-5 carbon is more reactive than the C-3 carbon toward nucleophiles. The reaction mechanism is discussed.     

Synthesis of certain alkenyl purines and purine analogs

Synthesis of alkenyl derivatives of certain purines and purine analogs is described. Direct alkylation of the sodium salt of 6-chloropurine (1) either with 1-bromo-2-pentene or 4-bromo-2-methyl-2-butene in N,N-dimethylformamide furnished N-7, 4a and N-9, 3a , 3b alkenyl derivatives. Similar alkylation of 2-amino-6-chloropurine (2) provided the corresponding N-7, 4c-4e and N-9, 3c-3e alkenyl derivatives. Acid hydrolysis of these chloro derivatives 3a-3e, 4a,c-e furnished the corresponding alkenyl hypoxan-thines 6a, 6b and 7a or alkenyl guanines 6c-6e and 7c-7e. Treatment of 3a-3d with thiourea in absolute ethanol provided the corresponding 6-thio derivatives 5a-5d. Alkylation of the sodium salt of either purine-6-carboxamide (8) or 1,2,4-triazole-3-carboxamide (10) gave mainly one isomer 9a, 9b and 11a, 11b. The direct alkylation of pyrrolo[2,3-d]pyrimidin-4(3H)-one (12) gave N-3 alkenyl derivatives 13a, 13b , and the N-7 alkenyl derivatives 16a, 16b have been prepared starting from the 4-chloro derivative 14 . Synthesis of 2-amino-7-(2-penten-1-yl)pyrrolo[2,3-d]pyrimidin-4(3H)-one (19a) has been accomplished starting from 2-amino-4-methoxypyrrolo[2,3-d]pyrimidine (17) . These alkenyl derivatives were found to be devoid of anti-HCMV activity in vitro.     

Synthesis of 2-carbethoxybenzofuran derivatives

A mixture of 3-formyl and 3-acetoxymethyl derivatives is formed in the oxidation of 2-carbethoxy-3-methyl-7-ethylbenzofuran with selenium dioxide. Reduction with lithium aluminum hydride gives 2,3-dihydroxymethyl derivatives, which are converted to 2,3-diformyl derivatives by successive oxidation. A number of derivatives of 3-methyl-7-ethylbenzofurancarboxylic acid were obtained.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 756–759, June, 1987.     

Azasteroids. Synthesis by Diels-Alder Reaction between Maleimides, Citraconimide, and Triazolindiones and 1-(1-Trialkylsiloxyvinyl)-3,4-dihydronaphthalene Derivatives

Summary. 18-Nor-16-azaestrane derivatives with 8β, 13β, and 14β orientation were isolated from Diels-Alder reactions between maleimides or citraconimide and 1-(1-siloxyvinyl)naphthalene derivatives. (8RS)-13,14,16-Triazaestrane derivatives were synthesized from 1,2,4-triazolin-3,5-diones. The parent 11-oxo derivatives were obtained by desilylation, and they were transformed into 11-hydroxyimino derivatives. 3-Hydroxy derivatives, finally were synthesized by cleavage of the 3-methoxy group with BBr₃. During these transformations the stereochemistry of the steroidal skeleton was not changed. The stereochemistry of these “unnatural” steroids was elucidated by spectroscopic methods, and compared with results from calculations, and with the configuration of natural estrane derivatives. Finally, an improved method for the synthesis of the starting material, 6-methoxy-1-[(1-trialkylsiloxy)-vinyl]-3,4-dihydronaphthalene was developed.     

Novel Synthesis and Structure of Phosphanyl Sugar Derivatives 1

Abstract

Some phosphanyl sugar derivatives, which are analogs of sugars having a phosphorus atom in place of the ring oxygen, were synthesized from 2- and 3-phospholenes as starting materials. Catalytic cis-dihydroxylation of 2-phospholene or 3-phospholene 1-oxide derivatives with osmium(VIII) oxide in the presence of a cooxidant afforded 3-deoxy- or 1-deoxy-tetrofuranose-type phosphanyl sugar derivatives, respectively. cis- Dihydroxylation of 4-acyloxy-2-phospholene 1-oxide derivatives gave tetrofuranose type phosphanyl sugar derivatives. Some of these derivatives of phosphanyl sugars were subjected to structural analyses using ¹H NMR and X-ray crystallography.

     

Synthesis of 1,4-diazines by ring expansion of 1,3-diazines

Fully saturated piperazin-3-one and quinoxalin-3-one derivatives were prepared by reactions of 2-anilino-2-ethoxy-3-oxothiobutanoic acid anilide with aliphatic 1,2-diamines. An unusual ring expansion of the intermediate 1,3-diazines leads to 1,4-diazines. Moreover, quinoxalin-3-one derivatives from chiral trans-1,2-diaminocyclohexane were obtained with diastereoselectivity >95%.     

Synthesis of 2,3-diformyl-5-ethylbenzofuran and its derivatives

A mixture of 3-formyl and 3-acetoxymethyl derivatives is formed in the oxidation of 2-carbethoxy-3-methyl-5-ethylbenzofuran with selenium dioxide. Reduction of the products with lithium aluminum hydride gives the corresponding 2,3-dihydroxymethyl derivatives, which are converted to 2,3-diformyl derivatives by successive oxidation by the Fetizon method and with manganese dioxide. The corresponding benzofuro[2, 3-d]pyridazines were synthesized by reaction of 2-carbethoxy-3-formyl-5-ethylbenzofuran with hydrazine hydrate.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 893–895, July, 1982.     

Vilsmeier formylation of 2-methyl-3 -carbethoxy-5-methoxy- and 2-methyl-5-methoxyindoles

The corresponding 6- and 3-formyl derivatives were obtained by formylation of 2-methyl-3-carbethoxy-5-methoxy- and 2-methyl-5-methoxyindole derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 339–341, March, 1971.     

Synthesis of 4‐(2‐hydroxyphenyl)‐1‐phenyl‐1,2,4‐triazolidine‐3,5‐dione derivatives through cyclic transformations of 3‐(2‐phenylcarbazoyl)‐2(3H)‐benzoxazolone derivatives

Four 3‐(3‐benzylidene‐2‐phenylcarbazoyl)‐2(3H)‐benzoxazolone derivatives 3 have been synthesized from benzoxazolone derivatives 1 and benzaldehyde N‐chloroformylphenylhydrazone 2. By acid hydrolysis, these compounds yielded 3‐(2‐phenylcarbazoyl)‐2(3H)benzoxazolone derivatives 4 which were not isolated and were transformed via an intramolecular reaction into 4‐(2‐hydroxyphenyl)‐1‐phenyl‐1,2,4‐triazolidine‐3,5‐dione derivatives 5 in a good yield. Attempts to cyclize these compounds by intramolecular elimination of water into tricyclic compounds 6 with various dehydrating agents were unsuccessful.     

Azo coupling and aminomethylation of 2,5-diphenylpyrrole and its derivatives

The azo coupling of 2,5-diphenylpyrrole with arenediazonium chlorides has given previously unknown 3-arylazopyrroles and 4-phenylazo-3-phenylhydrazono-3H-pyrrole. The methylation and reductive acetylation of the anylazo derivatives have led to N-methylarylazo and acetylamino derivatives of 2,5-diphenylpyrrole. 3-Amino-2, 5-diphenylpyrrole has been obtained by the reduction of 3-p-chlorophenylazo-2,5-diphenylpyrrole. The aminomethylation of 2,5-diphenylpyrrole and its derivatives with bis(dialkylamino)methanes had led to aminomethyl derivatives.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5. pp. 612–615, May, 1986.     

Synthesis of 3-Hydroxy-6-Methyl- and 3-Hydroxy-2-(2-phenylethyl)pyridines and Their Sulfur-Containing Amino and Hydroxymethyl Derivatives

The aminomethylation of 3-hydroxy-6-methyl- and 3-hydroxy-2-(2-phenylethyl)pyridines by secondary amines has been investigated. It was shown that like 2-alkyl-3-hydroxypyridine aminomethylation is directed primarily to position 6 and then 4 of the pyridine ring. On heating the aminomethyl derivatives of 3-hydroxy-6-methyl- and 3-hydroxy-2-(2-phenylethyl)pyridines with acetic anhydride the corresponding acetoxy derivatives were obtained, which were converted on heating with hydrochloric or hydrobromic acids into hydroxy and bromomethyl derivatives. Isothioureidomethyl and benzimidazolylthiomethyl derivatives were synthesized by heating the bromomethyl-substituted derivative with thiourea or with 2-mercaptobenzimidazole. The structures of compounds were confirmed by data of ¹H NMR spectra. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1189–1194, August, 2005.     

1,3-dipolar cycloadditions of arylnitrile oxides and 2-diazopropane with 5-hydroxy-3-methyl-1,5-dihydropyrrol-2-one derivatives

The reactions of arylnitrile oxides 2 and 2-diazopropane 5 with 5-hydroxy-3-methyl-1,5-dihydropyrrol-2-one derivatives 1 have been studied. 1,3-dipolar cycloaddition of arylnitrile oxides and 2-diazopropane with 5-hydroxy-3-methyl-1,5-dihydropyrrol-2-one derivatives is taking place regiospecifically. The asymmetric induction expected by the chiral centre of the 5-hydroxy-3-methyl-1,5-dihydropyrrol-2-one derivatives was very effective, diastereoisomers 3 and 4 were formed in an approximate 90:10 ratio. The stereoselectivity of the 1,3-dipolar cycloaddition of the 2-diazopropane with the 5-hydroxy-3-methyl-1,5-dihydropyrrol-2-one derivatives are investigated. The attack of the 1,3-dipole occurred from the less hindered face of the dipolarophile, giving the isomer 6.     

Synthesis of coumestan derivatives via FeCl3-mediated oxidative ring closure of 4-hydroxy coumarins

A concise and efficient approach to the syntheses of coumestan analogues has been developed. The underpinning strategy involves a FeCl(3)-mediated direct intramolecular oxidative annellation of 4-hydroxy-3-phenyl-2H-chromen-2-one derivatives. Utilizing this synthetic protocol, a variety of coumestan derivatives were conveniently obtained from readily available reagents.     

Investigations in the field of 2, 1,3-thiadiazole and 2, 1,3-selenadiazole

Benzo-2, 1, 3-selenadiazole and its derivatives readily undergo nitration with sodium nitrate in concentrated sulfuric acid with the formation, usually in high yield, of the corresponding mononitro and dinitro derivatives. The initial benzp-2, 1, 3-selenadiazoles were synthesized from selenium dioxide and o-diamines. The latter were obtained by reducing o-nitroaniline with sodium dithionite or by the reductive cleavage of the corresponding derivatives of benzo-2,1, 3-thiadiazole.For part XLIX, see [14].     

Syntheses of (4,1-benzoxazepine-3-ylidene)acetic acid derivatives and their inhibition of squalene synthase

The (3,5-trans)-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid derivatives 1 have been previously identified as potent squalene synthase inhibitors. A series of (4,1-benzoxazepin-3-ylidene)acetic acid derivatives were synthesized and evaluated for their inhibition of rat and human squalene synthase, and the (E)-isomers were found to exhibit potent inhibitory activity, with the same potency as 4,1-benzoxazepine-3-acetic acid derivatives. In contrast the (Z)-isomers did not exhibit significant inhibitory activity, and the active conformation of the 4,1-benzoxazepine-3-acetic acid derivatives was deduced from the folded conformation of the (E)-isomers.     

Electrochemical partial fluorination of organic compounds. 74. Efficient anodic synthesis of 2-fluoro- and 2,3-difluoro-2,3-dihydrobenzofuran derivatives

Anodic fluorination of 3-substituted benzofuran derivatives in a variety of fluoride salts resulted in the formation of three fluorinated products; two stereoisomers of 2,3-difluoro-2,3-dihydrobenzofuran (cis and trans) and cis-2-fluoro-3-hydroxy-2,3-dihydrobenzofuran derivatives. Dehydrofluorination of the main products, cis-difluoro derivatives, furnished the nonaromatic 2-fluoro-3-benzofuranyledene derivatives instead of the aromatic 2-fluorobenzofuran derivatives.