Novel N-chlorinated derivatives of 2H-1-benzopyran-2-imines

A series of new N-chlorobenzopyran-2-imines were prepared in moderate to good yields, by reacting sodium hypochlorite in an acidic medium with benzopyran-2-imines obtained via the Knoevenagel condensation. Some of the N-chlorobenzopyran-2-imines obtained are potential antiproliferating agents.     

Benzazoles: II. Synthesis and arenesulfonylation of 1-methyl-1H-benzimidazol-2-amine

The reaction of 1-methyl-1H-benzimidazol-2-amine with arenesulfonyl chlorides in the presence of triethylamine afforded 1-arenesulfonyl-3-methyl-2,3-dihydro-1H-benzimidazol-2-imines instead of expected N-(1-methyl-1H-benzimidazol 2-yl)arenesulfonamides.     

A new approach to the synthesis of strained cyclic systems: II. Mass spectrometric study of 2-dialkylamino-3-phenylthiophenes and their structural isomers, iminothietanes and iminocyclobutenes

Triads of isomeric N-alkyl-N-methyl-3-phenylthiophen-2-amines, N-methyl-3-alkyl-4-methylidene-3-phenylthietan-2-imines, and N-methyl-4-alkylsulfanyl-2-phenylcyclobut-2-en-1-imines (Alk = Me, Et, Bu) were synthesized from 1,3-dilithio-3-phenylpropyne, methyl isothiocyanate, and alkyl halides, and their fragmentation under electron impact was studied. Primary decomposition of the molecular ions of 2-aminothiophenes is determined by the localization of a radical cation center on the nitrogen atom, and it follows a path typical of alkyl(aryl)amines with elimination of hydrogen atom or methyl or propyl radical from the α-carbon atom in the N-alkyl substituent. Fragmentation of the iminothietanes involves cleavage of the four-membered ring in half to give neutral MeNCS molecule and 1-alkyl-1-phenylallene radical cation. Alkylsulfanyl(imino)-cyclobutenes undergo cleavage at the sulfur-containing side chain according to general relations holding in the fragmentation of alkyl sulfides.     

Single step synthesis of 2,3-dialkyl-6-nitro-quinazolin-4(3H)-imines and 3,5-dialkyl-9-nitro-imidazo[1,2-c]quinazolin-2(3H)-ones

A single step synthesis of 2,3-dialkyl-6-nitro-quinazolin-4(3H)-imines and 3,5-dialkyl-9-nitro-imidazo-[1,2-c]-quinazolin-2(3H)-ones from simple carbonyl compounds, primary amines or amino acid methyl esters and 2-azido-5-nitro-benzonitrile was developed. Key intermediates were N,N′-disubstituted amidines obtained by rearrangement of 4,5-dihydrotriazoles; the new heterocyclic rings were formed by spontaneous intramolecular reaction of the amino and cyano groups which are present in the intermediates.     

New,simple, and efficient method for the synthesis of N-substituted 4-trifluoromethyl-5-(alkan-1-ol)-pyridin-2(1H)-imines

A new, simple, and efficient method for the synthesis a novel series of 1-substituted 4-(trifluoromethyl)-5-(alkan-1-ol)-pyridin-2(1H)-imines from the reaction of 3-(5,6-dihydro-4H-pyran-3-yl)-4,4,4-trifluorobut-2-enenitrile and 3-(4,5-dihydrofuran-3-yl)-4,4,4-trifluorobut-2-enenitrile with primary amines – is described. The products were obtained in 29–82% yield.     

New atropoisomeric alkenylphenylglycine derivatives: Synthesis of (5R*)- and (5S*)-isomers of (1R*,3aR*,4S*,11S*)-3a,5,9,11-tetramethyl-4,5-dihydro-3aH-1,4-methano[1,3]oxazolo[3,2-a]quinolin-2-one

We synthesized methyl ester of N-(1-methylbut-2-en-1-yl)-N-phenylglycine which underwent acid catalyzed aromatic amino Claisen rearrangement to provide methyl-N-[2-(1-methylbut-2-en-1-yl)phenyl]glycinate. A mixture of syn- and anti-atropisomeric methyl-N-acetyl-N-[4-methyl-2-(1-methylbut-2-en-1-yl)phenyl]glycinates was obtained either by the reaction of this ester with acetyl bromide or by the reaction of the sodium salt of N-acetyl-2-(1-methylbut-2-en-1-yl)-4-methylaniline with methyl bromoacetate. Upon saponification of the synthesized ester mixture the syn-atropisomer of N-acetyl-N-[4-methyl-2-(1-methylbut-2-en-1-yl)phenyl]glycine was isolated by fractional crystallization. Treatment of the obtained acids with acetic anhydride, ethyl chloroformate, dicyclohexylcarbodiimide or isopropenylacetate leads to compounds of 4,5-dihydro-3aH-methano[1,3]oxazolo[3,2-a]quinolin-2-one structure.     

Modification of biologically active amides and amines with fluorine-containing heterocycles 6. Methyl 3,3,3-trifluoro-2-(3-methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)propionate in cyclocondensation with 1,3-binucleophiles

A reaction of methyl 3,3,3-trifluoro-2-(3-methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)propionate with 1,3-binucleophiles (N-benzylurea, N-substituted 3-aminocrotonates, N-substituted 3-aminocyclohexenones, and 6-aminouracyls), leading to the formation of fluorine-containing heterocyclic 3-methyl-1-phenylpyrazol-5-one derivatives, was studied.     

Effect of substitutents on the tautomeric equilibrium of 5-hydroxy-1,4-naphthoquinon-4-imines

Tautomeric equilibria ofpara- andana- quinoid forms of 5-hydroxy-1,4-naphthoquinone-4-imines in solutions were studied by UV and¹H NMR spectroscopy. Theana-form is electron-withdrawing substituents at position 6. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 358–362, February, 1997.     

Reaction of hexafluoro-N-(4-N,N-dialkylaminophenyl)-1,4-naphthoquinon-4-imines with primary amines

Amination of 2,3,5,6,7,8-hexafluoro-N-(4-N,N-dialkylaminophenyl)-1,4-naphthoquinon-4-imines with primary amines led to the formation of 3-amino derivatives, which further underwent cyclization into 7-alkyl(aryl)-1,2,3,4,6-pentafluoro-5H-benzo[a]phenazin-5-ones. The spectral properties of compounds obtained were examined.     

Reactions of fluoroalkanesulfonyl azides with cyclic vinyl ethers

The addition reactions of fluoroalkanesulfonyl azides to dihydropyran or dihydrofuran were studied. These reactions do not give the corresponding N-fluoroalkanesulfonyl azilidines but N-fluoroalkanesulfonyl-tetrahydropyranon-2-imines or N-fluoroalkanesulfonyl-tetrahydro-furano-2-imines. The reaction mechanism is discussed.     

The dramatic effect of thiophenol on the reaction pathway of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with thiophenolates: ring expansion versus nucleophilic substitution

Ethyl 4-methyl-2-oxo-7-phenylthio-2,3,6,7-tetrahydro-1H-1,3-diazepine-5-carboxylate and/or ethyl 6-methyl-2-oxo-4-(phenylthiomethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate were obtained in the reaction of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with PhSNa or PhSK with or without PhSH, depending on the reagent ratio, reaction time, or temperature, as a result of ring expansion and/or nucleophilic substitution. The reaction pathway was affected strongly by the basicity-nucleophilicity of the reaction media. The results obtained were confirmed by reactions of 4-mesyloxymethyl-6-methyl-5-tosyltetrahydropyrimidin-2-one with PhSNa/PhSH and ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with NaCN/HCN or NaCH(COOEt)₂/CH₂(COOEt)₂.     

Synthesis of novel ferrocene-containing 1,3-thiazinan-2-imines: One-pot reaction promoted by ultrasound irradiation

A simple one-pot synthesis of new ferrocene-containing 1,3-thiazinan-2-imines from 3-arylamino-1-ferrocenylpropan-1-ols and phenyl isothiocyanate has been developed. The key intermediate β-hydroxy thioureas were generated in situ using ultrasound irradiation and subsequent cyclization was achieved by the addition of acetic acid. The scope of the reaction towards various 3-arylamino-1-ferrocenylpropan-1-ols has been explored and the corresponding 3-aryl-6-ferrocenyl-N-phenyl-1,3-thiazinan-2-imines were obtained in moderate to high yields (52–90%).     

Rhodium-catalyzed reactions of 3-diazoindolin-2-imines with enamines and their extensions towards 5H-pyrazino[2,3-b]indoles

The rhodium-catalyzed reactions of 3-diazoindolin-2-imines with β-enamino esters furnished 2,3-diaminoindoles in excellent yields with wide functional group tolerance. The synthesized 2,3-diaminoindoles could be converted into 5H-pyrazino [2,3-b]indoles via a sequential dehydrogenation/6π-ERC/aromatization process.     

Nitropyrazoles: XII. Transformations of the 4-Methyl Group in 1,4-Dimethyl-3,5-dinitropyrazole and Cyclization of the Transformation Products

A preparative procedure for the synthesis of 1,4-dimethyl-3,5-dinitropyrazole by nitration of 1,4-dimethylpyrazole was developed. The reaction of 1,4-dimethyl-3,5-dinitropyrazole with dimethoxymethyl- (dimethyl)amine (N,N-dimethylformamide dimethyl acetal) gave (E)-N,N-dimethyl-2-(1-methyl-3,5-dinitropyrazol- 4-yl)ethenylamine. Acid hydrolysis of the latter afforded (1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde, and the reaction with sodium nitrite in hydrochloric acid led to formation of 2-hydroxymino-2-(1-methyl- 3,5-dinitropyrazol-4-yl)acetaldehyde. The corresponding O-methyloxime and phenylhydrazone reacted with K₂CO₃ to give 6-methyl-4-nitropyrazolo[4,3-d]isoxazole-3-carbaldehyde O-methyloxime and 1-methyl-3-nitro-4-(2-phenyl-2H-1,2,3-triazol-4-yl)pyrazol-5-ol, respectively. Treatment of (1-methyl-3,5-dinitropyrazol-4-yl)-acetaldehyde with benzenediazonium chloride gave (1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde phenylhydrazone which underwent intramolecular cyclization with replacement of the 5-nitro group by the action of K₂CO₃ in acetonitrile; in the reaction with K₂CO₃ in ethanol, the 5-nitro group was replaced by ethoxy.     

Catalyst free,regioselective one-pot three-component synthesis of thiazol-2-imine derivatives in ionic liquid

A one-pot three-component approach for the synthesis of thiazol-2-imines has been described by the reaction of amine, phenyl isothiocyanate and β-nitroacrylate in [Hbim]BF₄ ionic liquid. The method is applicable for aromatic, benzylic, aliphatic and cyclic amines. Reusable reaction media, regioselectivity, mild reaction condition, catalyst free and high yield of products are the salient features of this protocol.     

Synthesis of 3-alkylamino-3-(2-hydroxyaryl)-1-polyfluoroalkylprop-2-en-1-ones and 2-polyfluoroalkyl-4H-chromen-4-imines

Condensation of Schiff"s bases (prepared from 2-hydroxy- or 2-hydroxy-5-methylacetophenones and primary amines) with ethyl polyfluoroalkanoates in the presence of LiH in THF affords 3-alkylamino-3-(2-hydroxyaryl)-1-polyfluoroalkylprop-2-en-1-ones, which undergo cyclization in acidic media into 2-polyfluoroalkyl-4H-chromen-4-iminium salts. When neutralized with aqueous ammonia, the latter give 2-polyfluoroalkyl-4H-chromen-4-imines in high yields.     

Diastereoselective synthesis of 5-benzylthio- and 5-mercaptohexahydropyrimidin-2-ones

A three-stage diastereoselective synthesis of (4R^∗,5R^∗,6S^∗)-5-mercapto-4-methyl-6-phenylhexahydropyrimidin-2-one has been developed. The first stage involves the formation of 4-hydroxy-5-(4-methoxybenzylthio)-4-methyl-6-phenylhexahydropyrimidin-2-one by the reaction of N-[(phenyl)(tosyl)methyl]urea with the sodium enolate of 1-(4-methoxybenzylthio)propan-2-one. Reduction of the obtained compound by NaBH₄-CF₃COOH and removal of the p-methoxybenzyl protecting group results in the target compound.     

Synthesis,Structure and Cytotoxicity Testing of Novel 7-(4,5-Dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-Imine Derivatives

The appropriate 1-arylhydrazinecarbonitriles 1a–c are subjected to the reaction with 2-chloro-4,5-dihydro-1H-imidazole (2), yielding 7-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-imines 3a–c, which are subsequently converted into the corresponding amides 4a–e, 8a–c, sulfonamides 5a–n, 9, ureas 6a–I, and thioureas 7a–d. The structures of the newly prepared derivatives 3a–c, 4a–e, 5a–n, 6a–i, 7a–d, 8a–c, and 9 are confirmed by IR, NMR spectroscopic data, as well as single-crystal X-ray analyses of 5e and 8c. The in vitro cytotoxic potency of these compounds is determined on a panel of human cancer cell lines, and the relationships between structure and antitumor activity are discussed. The most active 4-chloro-N-(2-(4-chlorophenyl)-7-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)benzamide (4e) and N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-[1,1′-biphenyl]-4-sulfonamide (5l) inhibits the growth of the cervical cancer SISO and bladder cancer RT-112 cell lines with IC₅₀ values in the range of 2.38–3.77 μM. Moreover, N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-phenyl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-4-phenoxybenzenesulfonamide (5m) has the best selectivity towards the SISO cell line and induces apoptosis in this cell line.     

Highly regioselective direct halogenation: a simple and efficient method for preparing 4-halomethyl-5-methyl-2-aryl-1,3-thiazoles

An unprecedented C4-methyl regioselective halogenation of 4,5-dimethyl-2-aryl-1,3-thiazoles (1) has been accomplished. The reaction of compound 1 with N-chlorosuccinimide and N-bromosuccinimide under mild conditions provides an efficient and operationally simple method for obtaining 4-chloromethyl-5-methyl-2-aryl-1,3-thiazoles (2) and 4-bromomethyl-5-methyl-2-aryl-1,3-thiazoles (3), respectively, in good yields without the formation of 4-methyl-5-halomethyl regioisomers.     

Solvent-dependent Baylis–Hillman reactions for the synthesis of 3-benzyl-3-hydroxyoxindoles and benzo-δ-sultams

We have developed a solvent-dependent method for the preparation of novel benzo-δ-sultam and 3-benzyl-3-hydroxy-N-methyloxindole scaffolds. A variety of 3-(methoxy(phenyl)methyl)-1-methyl-1H-benzo-[c][1,2]thiazine 2,2-dioxides and 3-benzyl-3-hydroxy-1-methylindolin-2-ones were obtained in moderate to high yields via DBU-catalyzed Baylis–Hillman reaction of a number of (E)-N-(2-formylphenyl)-N-methyl-2-phenylethenesulfonamides in DMF and MeOH, respectively. The proof of the structures relies on analytical investigation and X-ray crystallography. Whereas reaction of (E)-N-(2-formylphenyl)-N-methyl-2-phenylethenesulfonamides in MeOH presumably proceeds through intramolecular Baylis–Hillman/dehydration, 3-hydroxy-N-methyloxindoles seem to have been generated via intramolecular Baylis–Hillman/1,3-H shift/oxidation/intramolecular cyclization tandem sequences in DMF.