Synthesis of novel 3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones

An efficient method for the synthesis of novel 3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones from various 2-dimethylaminomethylidenecyclohexane-1,3-diones, (1,3-thiazol-2-yl)acetonitriles, and dimethylformamide dimethyl acetal was developed. These transformations proceeded through intermediate 2-[2-(4-aryl-1,3-thiazol-2-yl)-2-cyanoethenyl]-3-oxocyclohex-1-en-1-olates. They were isolated as piperidinium salts and used in further heterocyclization reactions with aromatic amines, giving novel 1-aryl-3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones. These compounds were also obtained by preparative three-step “one pot” synthesis under controlled microwave irradiation. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 412–417, February, 2008.     

Synthesis of 3S-methylundec-1-ylbromide, a key synthon in the synthesis of (S,S,S)-diprionylacetate, from L-(-)-menthol

Three new approaches to the synthesis of 1-bromo-3S-methylundecane, a key synthon in the synthesis of (S,S,S)-diprionylacetate, a sex pheromone of pine sawflies of the genera Diprion and Neodiprion, were proposed based on chemo-and stereoselective transformations of L-(-)-menthol derivatives. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 73–76, January–February, 2006.     

Molecular and crystal structures of stereoisomeric2R,3R,6S-2-(1′S-hydroxy-1′-biphenylyl)- and2R,3R,6S-2-(1′R-hydroxy-1′-biphenylyl)methyl-3-methyl-6-isopropylcyclohexanones

It was established by X-ray diffraction analysis that 2-(1′-hydroxy-1′-biphenylyl)methyl-3-methyl-6-isopropylcyclohexanone, one of the minor products of the directed aldol reaction of (−)-menthone bromomagnesium enolate with 4-phenylbenzaldehyde, has the2R,3R,6S, 1′R configuration. The characteristic features of the spatial structure of this β-hydroxyketone were compared with those of the major stereoisomeric product of the above-mentioned reaction. The latter has the2R,3R,6S,1′S configuration. In the crystals, both stereoisomers have the cyclohexanone ring in a chair-like conformation with the three substituents in equatorial positions and are characterized by the presence of the annelated (cis-fused) pseudoring with an −OH…O=C< intramolecular hydrogen bond. The structures of the stereoisomers differ in the orientation of the aryl group and the hydrogen atom at the C(1′) chiral center with respect to the cyclohexanone ring. The results of X-ray diffraction analysis were compared with the data of molecular mechanics calculation for the energetically most favorable conformations of the isolated molecules of β-hydroxyketones under study. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 11, pp. 2251–2257, November, 1998.     

Synthesis ofN-(3-azido-2-nitroxypropyl)-,N-(2,3-diazidopropyl)-, andN-(2-azido-3-methoxypropyl)-N-alkylnitramines

N-(3-Azido-2-nitroxypropyl)-N-alkylnitramines andN-(2,3-diazidopropyl)-N-alkylnitramines were prepared by nitration and azidation ofN-alkyl-N-(2-hydroxy-3-chloropropyl)sulfamates andN-(3-azido-2-hydroxypropyl)-N-alkylsulfamates. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 206–208, January, 1999.     

Reaction of 2-(2-oxoethylidene)furan-3(2H)-ones with isopropylidenehydrazides of aromatic carboxylic acids: Synthesis of 3-hydroxy-3-(2-oxoethyl)-2,3-dihydropyridazin-4(1H)-ones

3-Hydroxy-3-(2-oxoethyl)-6-phenyl-2,3-dihydropyridazin-4(1H)-ones were obtained by the reaction of methyl 3-oxo-5-phenylfuran-2(3H)-ylideneacetate or 2-[2-(4-chlorophenyl)-2-oxoethylidene]-5-phenylfuran-3(2H)-one with benzoic or p-nitrobenzoic isopropylidenehydrazides. Equilibrium C₍₅₎H and C₍₅₎H₂ tautomeric forms were detected in solutions of the 4-chlorophenyl derivatives in DMSO-d₆. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1156–1158, August, 2007.     

3-(2-Quinolyl)- and 3-(5-carbethoxyfuryl-2)coumarins

3-(2-Quinolyl)- and 3-(5-carbethoxyfuryl-2)coumarins were prepared by reaction of substituted salicylaldehydes and hetarylacetonitriles. Alkylation and acylation of 3-hetaryl-7-hydroxycoumarins were studied. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 432–434, September–October, 2005.     

Synthesis of (3RS)- and (3SR)-acetoxy-(3aRS,8bSR)-N-acetyl-5-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles

Stereoisomeric 3-acetoxy-5-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles differing by the configuration of the C³ atom were synthesized. The reaction of N-acetyl-6-(cyclopent-2-en-1-yl)-2-methoxyaniline with 50% hydrogen peroxide in the presence of Na₂WO₄-H₃PO₄ in AcOH gave (3RS,3aRS,8bSR)-N-acetyl-3-hydroxy-5-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole which was converted into the corresponding 3-O-acetyl derivative by treatment with acetic anhydride in pyridine. N-Acetyl-6-(cyclopent-2-en-1-yl)-2-methoxyaniline reacted with iodine in methylene chloride in the presence of NaHCO₃ to produce (3SR,3aRS,8bSR)-3-acetoxy-5-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole which was subjected to acetylation at the nitrogen atom by reaction with acetic anhydride. The structure of (3RS,3aRS,8bSR)-N-acetyl-3-hydroxy-5-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole was proved by X-ray analysis. Original Russian Text ? N.A. Likhacheva, A.A. Korlyukov, R.R. Gataullin, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 3, pp. 406–409.     

1-( p -Fluorophenyl)-2-(2′-pyridyl)ethanol and 1-( p -fluorophenyl)-2-(2′-pyridyl)ethene obtained from the condensation reaction of 2-picoline and p -fluorophenylaldehyde under catalyst-and solvent-free conditions

The novel intermediate 1-(p-fluorophenyl)-2-(2′-pyridyl)ethanol or 2-[2′-(1-hydroxy-1-(p-fluorophenyl)ethyl]pyridine and the corresponding novel dehydration compound 1-(p-fluorophenyl)-2-(2′-pyridyl)ethene or 2-[p-fluorophenylvinyl]pyridine were obtained from the condensation reaction of p-fluorophenylaldehyde and 2-picoline under catalyst-and solvent-free conditions. The intermediate 1-(p-fluorophenyl)-2-(2′-pyridyl)ethanol was obtained at 42 h reaction time and temperature of 120°C, respectively. ¹H-NMR, IR spectroscopic data of the 1-(p-fluorophenyl)-2-(2-pyridyl)ethanol clearly showed the presence of the-CH₂-CHOH-group. The compound was obtained as a white powder with m.p. 121–122°C and a yield of 8%. For 1-(p-fluorophenyl)-2-(2-pyridyl)ethene, the reaction conditions were similar, but the reaction temperature was increased to yield the double bond in the 1-(p-fluorophenyl)-2-(2′-pyridyl)ethene. At the reaction temperature of 140°C, the compound was a slightly brown powder with a m.p. of 78°C and yield of 18%. ¹H-NMR, IR spectroscopic data for the 1-(p-fluorophenyl)-2-(2′-pyridyl)ethene showed the presence of a double bond in trans configuration (-CH=CH-), characteristic of a styrylpyridine.     

3-(2-Pyridyl)coumarins

3-(2-Pyridyl)coumarins were prepared by reaction of substituted salicylaldehydes and 2-pyridylacetonitrile. Benzylation, acylation, and aminomethylation of 7-hydroxy-3-(2-pyridyl)coumarin was studied. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 428–431, September–October, 2005.     

Quantum chemical study of the transformation of 2-(N-alkylamino)-3-(indol-1-yl)-and 2-(N-alkylamino)-3-(indol-3-yl)maleimides by protic acids: Tandem hydride transfer/cyclization mechanism

The geometric parameters, the charge distribution, and the energetics of N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)-and N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimides and their conjugated acids were studied by density functional theory calculations at the B3LYP/6-31G(d) level. The mechanism of the tandem hydride transfer/cyclization sequence, which occurs after protonation of N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)-and N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimides, was analyzed. The investigation of the potential energy surface for the tandem hydride transfer/cyclization of the iminium cation that formed upon protonation revealed that the hydride transfer followed by intramolecular cyclization at position 7 of the indole fragment in N-methyl-2-(N-ethylanilino)-3-(indol-1-yl)maleimide is the preferable process, unlike alternative intramolecular cyclization involving the cationic center at the C(2) atom of the indole fragment and the benzene ring of the N-ethylaniline fragment of the indoleninium cation in N-methyl-2-(N-ethylanilino)-3-(indol-3-yl)maleimide. A study of the key intermediates of the assumed reaction mechanism demonstrated that these intermediates are actually stationary points on the potential energy surface (minima and transition states). Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2069–2073, December, 2006.     

Enantiospecific synthesis of (S)-(+)-3-methylheneicosan-2-one, an analog of the sex pheromone of the German cockroach (Blatella germanica L.) from (−)-(1R,4S)-menthone

An enantiospecific synthesis of (S)-(+)-3-methylheneicosan-2-one, an analog of the sex pheromone of the German cockroach (Blatella germanica L.), was carried out through selective transformations of (3R,6S)-3,7-dimethyloctane-6-olide obtained from (−)-menthonevia the Baeyer—Villiger reaction. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1071–1073, May, 1997.     

Chemistry of naphthazarin derivatives 13. Conformational analysis of 3-(alk-1-enyl)-2-hydroxy-1,4-naphthoquinones by quantum chemistry methods

The molecular structures of various conformers of 2-hydroxy-1,4-naphthoquinone; 3-(alk-1-enyl)-2-hydroxy-1,4-naphthoquinones; 2,5,8-trihydroxy-1,4-naphthoquinone; and 3-(alk-1-enyl)-2,5,8-trihydroxy-1,4-naphthoquinones were studied by density functional theory (B3LYP/6-31(d), B3LYP/6-31(d, p)) and ab initio (MP2/6-31G, MP2/6-31(d)) methods. The strengths of the intramolecular hydrogen bonds formed by the β-hydroxy group with the O atom at C(1) and with the double bond π-electrons of the alkenyl substituents in the quinonoid rings were estimated. The compounds studied mainly exist as rotamers with the former-type hydrogen bonds. The splitting of the quinonoid bands of the stretching vibrations of the β-hydroxy group in the IR spectra of 3-(alk-1-enyl)-2-hydroxy-1,4-naphthoquinones and 3-(alk-1-enyl)-2,5,8-trihydroxy-1,4-naphthoquinones in hexane solutions is due to the existence of rotamers formed upon internal rotation of the alkenyl substituent. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1667–1673, October, 2006.     

Molecular Structure and Conformational Composition of 1-[(Methylthio)methyl]-2-nitrobenzene (MTMNB): A Theoretical and Experimental Study

The conformational composition of gaseous MTMNB and the molecular structures of the rotational forms have been studied by electron diffraction at 130^∘C aided by results from ab initio and density functional theory calculations. The conformational potential energy surface has been investigated by using the B3LYP/6-31G(d,p) method. As a result, six minimum-energy conformers have been identified. Geometries of all conformers were optimized using MP2/6-31G(d,p), B3LYP/6-31G(d,p), and B3LYP/cc-pVTZ methods. These calculations resulted in accurate geometries, relative energies, and harmonic vibrational frequencies for all conformers. The B3LYP/cc-pVTZ energies were then used to calculate the Boltzmann distribution of conformers. The best fit of the electron diffraction data to calculated values was obtained for the six conformer model, in agreement with the theoretical predictions. Average parameter values (r_a in angstroms, angle α in degrees, and estimated total errors given in parentheses) weighted for the mixture of six conformers are r(C–C) = 1.507(5), r(C–C)_{ring, av} = 1.397(3), r(C–S)_av = 1.814(4), r(C–N) = 1.495(4), r(N–O)_av = 1.223(3), ∠(C–C–C)_ring = 116.0–122.5, ∠ C6–C4–C7 = 118.2(4), ∠ C–C–S = 113.6(6), ∠ C–S–C = 98.5(12), ∠ N–C–C4 = 121.9(3), ∠(O–N–C)_av = 116.8(3), ∠ O–N–O = 127.0(4). Torsional angles could not be refined. Theoretical B3LYP/cc-pVTZ torsional angles for the rotation about C–N bond, φ_C−N, were found to be 30.5–36.5^∘ for different conformers. As to internal rotation about C–C and C–S bonds, values of φ_C−C = 68–118^∘ and φ_C−S = 66–71^∘ were obtained for the three most stable conformers with gauche orientation with respect to these bonds. Some conclusions of this work were presented in a short communication in Russ. J. Phys. Chem. 2005, 79, 1701.     

Interaction of 3-amino-2-(isoxazol-3-yl)-4-methoxymethyl-6-methyl-thieno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridine with Raney nickel

3-Amino-2-(isoxazol-3-yl)-4-methoxymethyl-6-methylthieno[2,3-b]pyridine was synthesized by the reaction of 2(1H)-thioxopyridine-3-carbonitrile with 3-chloromethylisoxazole in the presence of two equivalents of KOH. Boiling of 3-amino-2-(isoxazol-3-yl)-4-methoxymethyl-6-meth-ylthieno[2,3-b]pyridine with Raney nickel results in 4-aminothieno[2,3-b;4,5-b′]dipyridine or 5-(4-amino-2-pyridyl)pyridine depending on the reaction conditions. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 669–670, March, 2008.     

Synthesis of (S)-6-methylhept-5-en-2-ol, the aggregation pheromone ofGnathotrichus sulcatus

An enantioselective (ee−50%) four-step synthesis of (S)-6-methylhept-5-en-2-ol (“sulcatol”), which is the aggregation pheromone ofGnathotrichus sulcatus, from 3S,7-dimethylocta-1,6-diene was developed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 713–717, April, 2000.     

Synthesis ofN-substituted 2-(5,6,7,8-tetrafluoro-4-oxo-1,4-dihydroquinolin-3-yl)glyoxylic acids

Methods for the synthesis of the earlier unknownN-substituted 2-(5,6,7,8-tetrafluoro-4-oxo-1,4-dihydroquinolin-3-yl)glycoxylic acids their esters from copper chelate of ethyl pentafluorobenzoylpyruvate were developed. The structure of intermediate ethyl 4-(R-amino)-2-oxo-3-pentafluorobenzoylbut-3-enoates is discussed. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1234–1239, July, 2000.     

Chemical transformations of reaction products of 2-methyl-3-(4-tolyl)-4(3<Emphasis Type="Italic">H</Emphasis>)-quinazolone with benzil and its 4,4′-derivatives

The reaction of 2-methyl-3-(4-tolyl)-4(3H)-quinazolone with benzil produces 2-[(Z)-3-oxo-2,3-diphenylprop-1-enyl]-3-(4-tolyl)-4(3H)-quinazolone, which is readily transformed into 2-(3,3-diphenylsuccinimido)-N-(4-tolyl)benzamide on dissolution in organic water-containing solvents. The rearrangement mechanism was suggested and investigated by the quantum chemical PM3 method. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 146–151, January, 2007.     

3,3,3-Trifluoro-<Emphasis Type="Italic">N</Emphasis>′-(3-trifluoromethylphenyl)-1,2-propanediamine and its <Emphasis Type="Italic">N</Emphasis>-mono-and <Emphasis Type="Italic">N,N</Emphasis>-dicarboxyethyl derivatives: synthesis,protolytic and complexation properties

3,3,3-Trifluoro-N′-(3-trifluoromethylphenyl)-1,2-propanediamine (5) was synthesized by the reaction of 2-diazo-1,1,1-trifluoro-3-nitropropane or 3,3,3-trifluoro-1-nitropropene with 3-aminobenzotrifluoride followed by the reduction of the nitro group. The Michael 1,4-addition of diamine 5 to acrylic acid occurs only at the N(1) atom and affords N-mono-or N,N-dicarboxyethyl derivatives 6 and 7, depending on the reactant ratio. Protolytic equilibria 5–7 in aqueous solutions were studied by pH-potentiometry and UV spectroscopy. Only the aliphatic amino group can be protonated in an aqueous solution, while the aromatic amino group remains unprotonated even in 12 M HCl. The stability constants of transition metal (Cu²⁺, Ni²⁺, Zn²⁺) complexes with ligands 5–7 were determined by pH-potentiometric titration. The stability of the complexes and selectivity of the ligands toward Cu²⁺ ions increase with an increase in the number of N-carboxyethyl groups. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2465–2469, November, 2005.     

Synthesis of novel N2-adamantyl derivatives of 2-amino-6-methyl-4(3H)-pyrimidinone as potential activators of tumor necrosis factor (TNF) release

A method has been developed for the synthesis of N²-adamantyl-2-amino-6-methyl-4(3H)-pyrimidinones based on the reaction of (adamant-1-yl)alkylamine with 2-(ethylsulfanyl)-6-methyl-4(3H)-pyrimidinone which can lead to the corresponding derivatives in which the exocyclic nitrogen atom and the adamantyl radical are separated by a hydrocarbon fragment. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1541–1544, October, 2006.     

Reduction of (<Emphasis Type="Italic">E</Emphasis>)-3-aryl-2-(thiazol-2-yl)acrylonitriles with lithium aluminum hydride

Reduction of (E)-3-aryl-2-(4-arylthiazol-2-yl)acrylonitriles with lithium aluminum hydride in dry ether afforded (Z)-1-amino-3-aryl-2-(thiazol-2-yl)prop-1-ene derivatives in 15 to 40% yields. The structure of (Z)-1-amino-3-(2-chlorophenyl)-2-[4-(4-methylphenyl)thiazol-2-yl]prop-1-ene was confirmed by X-ray diffraction analysis. Dedicated to Academician N. K. Kochetkov on the occasion of his 90th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1301–1303, May, 2005.