Imidazo[1,2-a]benzimidazole derivatives

3-Amino derivatives of 9-alkyl(benzyl)-2-arylimidazo[1,2-a]benzimidazoles, obtained by the reduction of the appropriate 3-nitro(nitroso) derivatives, are extremely unstable, and the imidazole ring opens readily resulting in conversion to 2-(-carboxybenzylamino)benzimidazoles. The reaction apparently proceeds through the intermediate formation of 2-(-cyanobenzylamino)benzimidazole, which is a tautomeric form of the 3-amino compound and can react as such to form 3-acylamino derivatives and anils. If there is a methyl group in the 3-position of the ring, the amine is quite stable and can be isolated in free form.See [1] for communication IV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 673–677, May, 1971.     

Reaction of 3-Methyleneisocamphanone with Derivatives of Malonic Acid

Reaction of 3-methyleneisocamphanone with malononitrile, ethyl cyanoacetate or diethyl malonate in the presence of catalytic quantities of alkali or under catalysis with tetramethylguanidine in ethanol proceeds according to classical scheme of the Michael reaction and gives rise to 3-exo-(2,2-dicyanoethyl)-, 3-exo-(2-cyano-2-ethoxycarbonylethyl)-, or 3-exo-(2,2-diethoxycarbonylethyl)isocamphanone respectively. When the reaction with ethyl cyanoacetate and diethyl malonate is carried out in methanol occurs transalkylation of the ester groups resulting in the corresponding methyl esters, and in THF occurs hydrolysis to form carboxylic acids. In ethanol or methanol in the presence of equimolar or excess amounts of alkali compounds with cyano groups suffer cyclization into the corresponding 2-alkoxy-3-cyano- or 1-alkoxy-3-alkoxycarbonyl-7,7,8-trimethylbicyclo[2.2.1]hepteno[2.3-b]pyridines. In THF partially form analogous tricyclic 2-hydroxypyridines.     

Azines and Azoles: CXX. Synthesis of Acyclic Analogs of N1-Ribosides of Barbituric Acid and Its 5-ylidene Derivatives

The reaction of 2,4,6-tris(trimethylsiloxy)pyrimidine with 2-oxabutane-1,4-diyl diacetate in methylene chloride in methylene chloride in the presence of SnCl₄ proceeds regioselectively to form 1-[(2-acetoxyethoxy)methyl]barbituric acid. The latter is readily deacetylated to a free acyclic analog of N-ribosides of barbituric acid. 1-[(2-Acetoxy- and 2-hydroxyethoxy)methyl]barbituric acids easily react with aromatic and heterocyclic aldehydes in water and organic solvents, forming 5-ylidenebarbituric acids. The structure of the products was proved by ¹H NMR and UV spectroscopy. Certain of the products exhibit a moderate antimicrobial and antiviral activity.     

Cascade Transformations of (2,2-Diaryl-3,3-dichloroaziridin-1-yl)acetates

Esters of (2,2-diaryl-3,3-dichloroaziridin-1-yl)acetic acid prepared from glycine derivatives under alkylation conditions afford esters of 2-[N-alkyl-N-(2,2-diaryl-1-cyanovinyl)amino]-3,3-diarylacrylic acid in 20-40% yield. The reaction resulting in these compounds proceeds through a cascade of 3-chloro-2-azadiene and ylide intermediates. 3-Chloro-2-azadienes originating from (2,2-diaryl-3,3-dichloroaziridin-1-yl)acetates react with primary and secondary amines at the carbon atom of imine group providing ketenimines which undergo ketenimine-nitrile rearrangement or fragmentation. The other bases (KOH, MeONa, DBU) effect dehydrochlorination of the mentioned 3-chloro-2-azadienes giving nitrile-ylides which are trapped by nucleophilic reagents. The 3-chloro-2-azadiene obtained from methyl (2,2-diaryl-3,3-dichloroaziridin-1-yl)acetate and DBU was relatively stable and was isolated as an individual compound. (2,2-diaryl-3,3-dichloroaziridin-1-yl)propionates behave as nonfunctionalized dichloroaziridines.     

Benzo[f]-3-aza- and -10-azafluoroanthenes

Reduction of 3-methyl-9-(o-tolyl)-2-azafluoren-9-ol (I) with tin in hydrochloric acid gave 3-methyl-9-(o-tolyl)-2-azafluorene, dehydrocyclization of which on a K-16 catalyst at 520–500°C gave a complex mixture, from which four substances — 2-methylbenzo[f]-3-azafluoranthene, 11-methylbenzo[f]-10-azafluoranthene, benzo[f]-3-azafluoroanthene (II), and I-were isolated and identified by means of the IR, UV, and PMR, and mass spectra. It is shown that the dehydrocyclization proceeds through the hydrogen atoms of the methyl group of the tolyl substituent and takes place at the 8-C or 1-C atom of the azafluorene system. The formation of products II and I constitutes evidence that the reaction is accompanied by partial demethylation or oxidation.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1245–1247, September, 1977.     

Competing processes in condensation of 3,3-bis(methylthio)-2-cyano-<Emphasis Type="Italic">N</Emphasis>-arylacrylamides with cyanoacetanilides

Reaction of cyanoacetanilides with 3,3-bis(methylthio)-2-cyano-N-arylacrylamides proceeds to form isomeric N,1-diaryl-1,6-dihydropyridine-3-carboxamides. A single crystal consisting of 2-amino-4-methylthio-N-(2-methoxyphenyl)-6-oxo-1-phenyl-5-cyano-1,6-dihydropyridine-3-carboxamide and 2-amino-4-methylthio-1-(2-methoxyphenyl)-6-oxo-N-phenyl-5-cyano-1,6-dihydropyridine-3-carboxamide was studied by XRD.     

Homogeneous and heterogeneous asymmetric reactions. Part 5. Diastereoselective and enantioselective hydrogenation of cyclic β-keto esters on modified Raney-nickel catalysts

The hydrogenations of methyl 2-oxoeyclopentanecarboxylate ( 1 ), ethyl 2-oxocyelohexanecarboxylate ( 3 ), and 2-methylcyclohexanone ( 5 ) on unmodified Raney-Ni catalyst lead predominately to the formation of the cis-hydroxy diastereoisomers of 2 , 4 , and 6 , respectively (Scheme 2). In the asymmetric hydrogenations on catalysts modified with chiral tartaric acid ((R, R )-C₄H₆O₆/Raney-Ni and (R, R)-C₄H₆O₆/NaBr/Raney-Ni), the predominance of the cis-isomer increases significantly. The hydrogenations of β-keto esters 1 and 3 proceed with an enantioselectivity of 10–15% on the modified catalysts, while the similar hydrogenation of 5 yields optically inactive 6 . The (1S,2R)-enantiomers of the cis-isomers of 2 and 4 are formed in larger quantity, whereas the (lR,2R)-enantiomers of the corresponding trans-isomers predominate (Scheme 1). The enantioselective formation of trans- 2 and trans- 4 can be interpreted mainly in terms of the asymmetric hydrogenation of cyclic β-keto esters through the keto form, while that of the corresponding cis-hydroxy esters proceeds through the enol form.     

Characterization and oxidative addition reactions for iridium cod complexes

Three different [Ir(LL′)(cod)] complexes (LL′ = N-aryl-N-nitrosohydroxylaminato) (cupf), trifluoroacetylacetonato (tfaa), and (methyl 2-(methylamino)-1-cyclopentene-1-dithiocarboxylato-κN,κS) (macsm)) were synthesized, characterized, and their rates of oxidative addition with methyl iodide were determined. Formation of an isosbestic point during the oxidative addition of methyl iodide with the complexes containing tfaa and cupf as bidentate ligands indicated formation of only one product, while an increase in absorbance maximum observed for macsm confirms that the same reaction between the complex and methyl iodide occurs. Kinetic results for all complexes, except [Ir(tfaa)(cod)], showed simple second-order kinetics with a zero intercept (within experimental error). Rates of oxidative addition for bidentate ligands in acetonitrile showed an increase of an order of magnitude with a change in the type of bidentate ligands. Computational chemistry using density functional theory calculations showed that the oxidative addition reaction proceeds through a “linear” transition state with the methyl iodide unit tilted towards the LL′-bidentate ligand.     

Reactions of spirocyclopropane-containing 1- and 2-pyrazolines with electrophilic reagents

Hydrochlorination of spiro(1-pyrazoline-3,1′-cyclopropanes) proceeds regioselectively at the azocyclopropane group to form 3-(2-haloethyl)pyrazoline derivatives. If the latter contain a halogen atom in the heterocycle, they are readily converted into (2-haloethyl)pyrazole hydrohalides. Bromination of 3-cyanospiro(2-pyrazoline-5,1′-cyclopropane) withN-bromosuccinimide at 20°C proceeds with retention of the cyclopropane ring to form 3-bromo-3-cyanospiro(1-pyrazoline-5,1′-cyclopropane), which is converted into (2-bromoethyl)cyanopyrazole in ∼60% yield at ∼20°C after 3–4 days.     

Transformations of 3-methyl-2-azafluorene involving the methyl and methylene groups

The condensation of 3-methyl-2-azafluorene with benzaldehyde at the methyl group, as a result of which the cis and trans forms of 3-styryl-2-azafluorene are formed, proceeds without catalysts. The subsequent condensation with benzaldehyde takes place in the presence of potassium ethoxide and leads to 3-styryl-9-benzylidene-2-azafluorene. Treatment of azafluorene with phenoxyacetyl chloride in the presence of triethylamine yielded 3-methyl-9-(-hydroxy--phenoxyethylidene)-2-azafluorene. On the basis of the spectral data it was concluded that the latter exists in the form of a mixture of the enol form and the zwitterionic form. 3-Methyl-9-(-phenyl--cinnamoyloxyallylidene)-2-azafluorene was obtained by acylation of azafluorene with cinnamoyl chloride under the same conditions. The PMR and IR spectral data are presented.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 79–81, January, 1978.     

Cyclization of a cysteine conjugate of N-(3,5-Dichlorophenyl)succinimide

N-(3,5-Dichlorophenyl)-2-cysteinylsuccinimide methyl ester hydrochloride ( 5 ) was prepared from N-(3,5-dichlorophenyl)maleimide ( 3 ) and cysteinyl methyl ester hydrochloride. Attempted neutralization of the cysteine conjugate salt with triethylamine resulted in spontaneous cyclization of 5 to form the more stable 2-(N-3,5-dichlorophenylcarbamoylmethyl)-5-carbomethoxy-1,4-thiazine- 3-one ( 6 ). Similar results might be expected in vivo should these metabolites of succinimides be formed.     

Strukturelle Abwandlungen an partiell silylierten Kohlenhydraten mittels Triphenylphosphin/Azodicarbonsäure-diäthylester. 3. Mitteilung [1]

Structural Modification on Partially Silylated Carbohydrates by Means of Triphenylphosphine/Diethyl Azodicarboxylate Reaction of methyl 2, 6-bis-O-(t-butyldimethylsilyl)-β-D -glucopyranoside ( 1a ) with triphenylphosphine (TPP)/diethyl azodicarboxylate (DEAD) and Ph₃P · HBr or methyl iodide yields methyl 3-bromo-2, 6-bis-O-(t-butyldimethylsilyl)-3-deoxy-β-D -allopyranoside ( 3a ) and the corresponding 3-deoxy-3-iodo-alloside 3c (Scheme 1). By a similar way methyl 2, 6-bis-O-(t-butyldimethylsilyl)-α-D -glucopyranoside ( 2a ) can be converted to the 4-bromo-4-deoxy-galactoside 4a and the 4-deoxy-4-iodo-galactoside 4b . In the absence of an external nucleophile the sugar derivatives 1a and 2a react with TPP/DEAD to form the 3,4-anhydro-α- or -β-D -galactosides 5 and 6a , respectively, while methyl 4, 6-bis-O-(t-butyldimethylsilyl)-β-D -glucopyranoside ( 1b ) yields methyl 2,3-anhydro-4, 6-bis-O-(t-butyldimethylsilyl)-β-D -allopyranoside ( 7a , s. Scheme 2). Even the monosilylated sugar methyl 6-O-(t-butyldimethylsilyl)-α-D -glucopyranoside ( 2b ) can be transformed to methyl 2,3-anhydro-6-O-(t-butyldimethylsilyl)-β-D -allopyranoside ( 8 ; 56%) and 3,4-anhydro-α-D -alloside 9 (23%, s. Scheme 3). Reaction of 1c with TPP/DEAD/HN₃ leads to methyl 3-azido-6-O-(t-butyldimethylsilyl)-3-deoxy-β-D -allopyranoside ( 10 ). The epoxides 7 and 8 were converted with NaN₃/NH₄Cl to the 2-azido-2-deoxy-altrosides 11 and 13 , respectively, and the 3-azido-3-deoxy-glucosides 12 and 14 , respectively (Scheme 4 and 5). Reaction of 7 and 8 with TPP/DEAD/HN₃ or p-nitrobenzoic acid afforded methyl 2,3-anhydro-4-azido-6-O-(t-butyldimethylsilyl)-4-deoxy-α- and -β-D -gulopyranoside ( 15 and 17 ), respectively, or methyl 2,3-anhydro-6-O-(t-butyldimethylsilyl)-4-O-(p-nitrobenzoyl)-α- and -β-D -gulopyranoside ( 16 and 18 ), respectively, without any opening of the oxirane ring (s. Scheme 6). - The 2-acetamido-2-deoxy-glucosides 19a and 20a react with TPP/DEAD alone to form the corresponding methyl 2-acetamido-3,4-anhydro-6-O-(t-butyldimethylsilyl)-2-deoxy-galactopyranosides ( 21 and 22 ) in a yield of 80 and 85%, respectively (Scheme 7). With TPP/DEAD/HN₃ 20a is transformed to methyl 2-acetamido-3-azido-6-O-(t-butyldimethylsilyl)-2,3-didesoxy-β-D -allopyranoside ( 25 , Scheme 8). By this way methyl 2-acetamido-3,6-bis-O-(t-butyldimethylsilyl)-α-D -glucopyranoside ( 19b ) yields methyl 2-acetamido-4-azido-3,6-bis-O-(t-butyldimethylsilyl)-2,4-dideoxy-α-D -galactopyranoside ( 23 ; 16%) and the isomerized product methyl 2-acetamido-4,6-bis-O-(t-butyldimethylsilyl)-2-deoxy-α-D -glucopyranoside ( 19d ; 45%). Under the same conditions the disilylated methyl 2-acetamido-2-deoxy-glucoside 20b leads to methyl 2-acetamido-4-azido-3,6-bis-O-(t-butyldimethylsilyl)-2,4-dideoxy-β-D -galactopyranoside ( 24 ). - All Structures were assigned by ¹H-NMR. analysis of the corresponding acetates.     

Intramolecular electrophilic cyclization of functional derivatives of unsaturated compounds: II. Synthesis and transformation of N-{(2Z)-5-[(arylsulfanyl)methyl]dihydrofuran-2(3H)-ylidene}-N-alkyl(aryl)aminium perchlorates

N-Alkyl(aryl)amides of allylacetic acid when reacting with arylsulfenyl chlorides in acetic acid in the presence of lithium perchlorate undergo a selective cyclization to form N-{(2Z)-5-[(arylsulfanyl)methyl] dihydrofuran-2(3H)-ylidene}-N-alkyl-(aryl)aminium perchlorates. Treating of the latter with sodium acetate leads to the formation of the corresponding 5-[(arylsulfanyl)methyl]lactones, and with sodium ethylate, to 5-[(arylsulfanyl) methyl]-2-iminolactones. In reaction with secondary cycloalkylamines in the presence of water a transamidation and tetrahydrofuran ring opening occurs to afford 5-arylsulfanyl-4-hydroxypentanoic acid amides.     

Fused polycyclic nitrogen-containing heterocycles 13. Synthesis of 6-phenyl-2-phenylimino-6H-1,3,4-thiadiazine-5-carboxylic acid and its intermolecular cyclodehydration accompanied by sulfur extrusion to form dipyrazolo[1,5-a,1′,5′d]pyrazine

Condensation of methyl phenylchloropyruvate with 4-phenylthiosemicarbazide proceeds as the Bose reaction to form 5-methoxycarbonyl-6-phenyl-2-phenylimino-6H-1,3,4-thiadiazine, which is hydrolyzed to give carboxylic acid. In the presence of polyphosphoric acid, the latter undergoes intermolecular cyclodehydration accompanied by sulfur extrusion to yield dipyrazolo [1,5-a,1′,5′d]pyrazine.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 432–435, February, 2005.     

Synthesis of Phaitanthrin E and Tryptanthrin through Amination/Cyclization Cascade

Phaitanthrin E was biomimetically synthesized from methyl indole‐3‐carboxylate and methyl anthranilate or anthranilic acid using the ester group as an activating group. The reaction proceeds through NCS‐mediated dearomatization/TFA‐catalyzed protonation of indolenine/C(2) amination/Et₃N‐promoted aromatization and cyclization in one‐pot procedure. This method is capable of converting simple biomass materials to phaitanthrin E. The synthesis not only allows assessment of antiproliferative activity, but also affords experimental support for the hypothetical biosynthetic pathway of phaitanthrin E. The resulting phaitanthrin E derivatives were evaluated for in vitro antiproliferative activity against human colorectal cancer cells (DLD‐1). The biogenetic intermediate of phaitanthrin E showed higher antiproliferative activity than the natural product, phaitanthrin E. Furthermore, a concise synthesis of tryptanthrin is also accomplished from indole‐3‐carbaldehyde and methyl anthranilate using the aldehyde group as an activating group.     

Difference in the behavior of methyl (S)-α-bromopropionate in its addition to trimethylvinylsilane depending on the method of initiation

The addition of methyl (S)-2-bromopropionate to trimethylvinylsilane initiated by systems based on iron pentacarbonyl affords a racemic adduct and is accompanied by racemization of the unreacted chiral ester. In the presence of benzoyl peroxide, the reaction proceeds similarly, but no racemization of the starting chiral ester occurs.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 715–718, March, 1996.     

Synthesis of isoxazolinylxanthines

1-[5-(3-Arylisoxazolin-2-yl)methyl]-3,7-dimethylxanthines have been synthesized by the [2+3] cycloaddition of arylnitrile oxides to allyltheobromine. 7-{5-[3-(2,4-Dichlorophenyl)isoxazolin-2-yl]methyl}-1,3-dimethylxanthine was obtained by the addition of 2,4-dichlorobenzonitrile oxide to allyltheobromine. The addition of arylnitrile oxides to structural isomers of methylxanthines proceeds regioselectively with the formation of 3,5-disubstituted isoxazolines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii. No. 2, pp. 245–248, February, 2007.     

Hydrogenolysis of the C?O bond of the 1,2,4-oxadiazine ring. Adams platinum hydrogenation of 3-aryl-5,6-dihydro-5-(substituted)-methylene-4H-1,2,4-oxadiazine derivatives

Adams platinum hydrogenation of Z-3-aryl-5,6-dihydro-5-(substituted)methylene-4H-1,2,4- oxadiazine ( 1a-f ) proceeds very slowly through C? O bond fission to give N-(1-substitutedcarbonyl-2-propylidene)benzamide ox-ime derivative 2 as the main product. In the reaction of 5-(arylcarbamoyl)methylene analogues 1d-f , 5-(aryl-carbamoyl)methyl-5,6-dihydro-3-phenyl-4H-1,2,4-oxadiazine ( 4 ) and N-aryl-3-hydroxybutanamide derivative 5 are also obtained as well as compound 2 .     

Facile Synthesis of Novel Functionalized Pyridine Annulated Oxirane Methyl Coumarins

A one‐pot synthesis of series of new ethyl‐7‐oxirane methyl‐2‐methyl‐5‐oxo‐5H‐benzopyrano[3,4‐c]pyridine‐1‐carboxylates ( 6a–e ) from 3‐allyl‐2‐hydroxy acetophenones ( 1a–e ) via key intermediate 8‐allyl‐4‐chloro‐3‐formyl coumarins ( 2a–e ) is described. The reaction involves Michael addition of 8‐allyl‐4‐chloro‐3‐formyl coumarins with ethyl 3‐amino crotonoate followed by cyclization, and per acid epoxidation proceeds under mild conditions and gives products in good‐to‐excellent yields.     

Über den Anteil sigmatroper 1, 5-Wanderung von Kohlenwasserstoffgruppen bei der thermolytischen Skelettisomerisierung 5,5-disubstituierter 1, 3-Cyclohexadiene

On the Extent of Sigmatropic 1, 5-Migration of Hydrocarbon Groups in the Thermolytic Skeletal Rearrangement of 5,5-Disubstituted 1,3-Cyclohexadienes The uncatalyzed skeletal isomerization of 5, 5-disubstituted 1, 3-cyclohexadienes was investigated with the aim to establish the extent to which sigmatropic 1,5-shifts of hydrocarbon groups are participating in these reactions. Gas phase pyrolysis of 5,5-diethyl-1,3-cyclohexadiene ( 7 ) at 460° followed by chloranil aromatization yields only 4% of 1,3-diethylbenzene resulting from 7 through a 1, 5-ethyl migration in the primary reaction step. 2, 3-Dimethylethylbenzene (56%) and 1, 4-diethylbenzene (4%) are obtained as other C₁₀-compounds. This shows that isomerization proceeds mainly through a sequence of electrocyclic and 1, 7-shift reactions. Ethylbenzene (24%) and other aromatic C₈- and C₉-hydrocarbons are formed to a considerable extent, indicating that C, C-bond cleavage is a major competing process and that the 1, 3-diethylbenzene found is the result of a radical recombination reaction and not of a concerted sigmatropic shift of the ethyl group. 5-Methyl-5-phenyl-1, 3-cyclohexadiene ( 12 ) yields 3-methylbiphenyl ( 14 ) and biphenyl upon thermolysis and aromatization. Through ¹³C-substitution of the methyl group in 12 it is shown that in solution at 300° skeletal isomerization proceeds through electrocyclic and 1, 7-H-shift reactions exclusively. In the gas phase at 500° 4% of the isomerization product is formed by a 1, 5-shift of a substitutent, presumably of the methyl group, through a dissociative mechanism. Thermolysis of 5, 5-diphenyl-1, 3-cyclohexadiene ( 22 ) at 560° in the gas phase leads to 1, 1-diphenyl-1, 3, 5-hexatriene ( 23 ) and 1-vinyl-4-phenyl-1, 2-dihydronaphthalene ( 24 ) through electrocyclic reaction steps. In addition a small amount of m-terphenyl is obtained at high conversion of 22 . This indicates that sigmatropic 1,5-phenyl migration can participate in product formation only at high temperature and in the absence of other irreversible pathways to stable products.