Crystal structure investigation of (4<Emphasis Type="Italic">S</Emphasis>,5<Emphasis Type="Italic">S</Emphasis>)-4-[(dichloroacetoxy)methyl]-5-(4-nitrophenyl)-2-oxazolidinone

The structure of (4S,5S)-4-[(dichloroacetoxy)methyl]-5-(4-nitrophenyl)-2-oxazolidinone has been determined by crystal structure investigation.     

Synthesis and characterization of novel 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and dihydro-alkylthio-benzyloxopyrimidine (S-DABO) analogs containing a benzo[<Emphasis Type="Italic">d</Emphasis>]thiazol moiety

A series of novel dihydro-alkylthio-benzyloxopyrimidine (S-DABO) and 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio)thymine (HEPT) analogs bearing a (benzo[d]thiazol-2-yl)methyl moiety at the C⁶ position of the pyrimidine core have been synthesized. 5-Allyl-6-{(benzo[d]thiazol-2-yl)methyl}-2-thiouracil and 5-allyl-6-{(benzo-[d]thiazol-2-yl)methyl}uracil were alkylated to give, respectively, S²- and N¹- ethoxymethyl and -methylthiomethyl uracil derivatives. 5-Allyl-6-[(benzo[d]thiazol-2-yl)methyl]-2-thiouracil was also alkylated by S² with methyl bromoacetate and hydrolyzed to the corresponding acid.     

Molecular rearrangements of (-)-modhephene and (-)-isocomene to a (-)-triquinane

The preparation and further rearrangement of (-)-modhephene (1) to a (-)-triquinane 5 has been assessed through acid catalysis. The rearrangement involved protonation, 1,2 sigma-bond and methyl shifts, and deprotonation. Monitored experiments by 1H NMR spectroscopy suggested the intermediate (-)-isocomene (3), which was further evidenced when a sample of natural (-)-3 undergoes acid-catalyzed conversion to the (-)-triquinane 5. In addition, deuterated (-)-modhephene (1-d) labeled stereospecifically at the 14beta geminal methyl group at C4 was synthesized, through the corresponding chiral deuterated primary alcohol, in 5 steps, starting from natural (-)-14-hydroxymodhephene (8), and rearranged under acid catalysis to elucidate the stereochemical factors that control the methyl shift at this position. The final deuterium-labeled (-)-triquinane, 5-d, obtained from [14-(2)H1]-1-d was established to have deuterium in the methyl group at C5 by 13C NMR spectroscopy. This stereoselective methyl migration is in accordance with the molecular orbital demand formulated by the quantum chemical calculations performed in the present study.     

Nitrile oxide cycloaddition routes to 2-(isoxazolyl)-benzoates and 2-(1,2,4-oxadiazol-3-yl)benzoates

Cycloaddition of aromatic nitrile oxides to methyl o-vinylbenzoate produced methyl 2-(3-aryl-2-isoxazolin-5-yl)benzoates; the isoxazolines were converted to methyl 2-(3-arylisoxazol-5-yl)benzoates. Reaction of the nitrile oxide from o-methoxycarbonylbenzohydroximinoyl chloride ( 11 ) with phenylacetylene, styrenes, and aromatic nitriles resulted in methyl 2-(5-phenylisoxazol-3-yl)benzoate, methyl 2-(5-aryl-2-isoxazolin-3-yl)-benzoates ( 15 ), and methyl 2-(5-aryl-1,2,4-oxadiazol-3-yl)benzoates, respectively. The isoxazolines 15 were converted to the corresponding isoxazoles 16 .     

Synthesis and Crystal Structure of (E)-2-(1-(2-Hydroxy-4-methoxyphenyl)ethylideneamino)-3-(4-hydroxyphenyl)methyl Propionate

(E)-2-(1-(2-Hydroxy-4-methoxyphenyl)ethylideneamino)-3-(4-hydroxyphenyl)methyl propionate (C22H27O6N, Mr = 401.45) has been synthesized by a condensation reaction of paeonol with tyrosin methyl ester hydrochloride, and its structure was determined by IR, NMR, HR MS and X-ray single-crystal diffraction. The crystal belongs to the monoclinic system, space group P21/c, with a = 11.91291(15), b = 9.49947(12), c = 19.8727(3) , β = 106.1104(15)°, V = 2160.60(5)3, Z = 4, Dc = 1.234 g/cm3, μ = 0.739 mm-1, F(000) = 856, R = 0.0466 and wR = 0.1461 for 3859 observed reflections with (Ⅰ> 2σ(Ⅰ)). In the crystal structure, the title compound is constructed by a centrosymmetric dimmer unit composed of a pair of π-π stacking enantiomers, and such units are linked by intermolecular O(5)-H(5)…O(1) and intramolecular N(1)-H(1)…O(1) hydrogen bonds.     

Regioselective cycloaddition of C-carbamoylnitrones to methyl (E)-2-(2-phenylcyclopropylidene)acetate and methyl (E)-2-methylidene-3-phenylcyclopropane-1-carboxylate

N-Aryl-C-(arylcarbamoyl)nitrones regioselectively add to methyl 2-(2-phenylcyclopropylidene)-acetate and methyl 2-methylidene-3-phenylcyclopropanecarboxylate to give in each case two diastereoisomeric 5-oxa-6-azaspiro[2.4]heptane-4-carboxylates.     

(-)-(R)- and (+)-(S)-Carvone in the Synthesis of Optically Active Acetylenic Alcohols,Ethers, and Dichlorosilyl Derivatives

Reaction of butyllithium with acetylene and 1-hexyne gave the corresponding lithium acetylides which reacted with (-)-(R)- and (+)-(S-carvone in a stereospecific fashion to give lithium (1-ethynyl- or 1-hexynyl)-5-isopropenyl-2-methyl-2-cyclohexenolates. Hydrolysis of the latter gave individual optically active tertiary terpene alcohols having both acetylenic and p-menthene fragment. Their treatment with methyl iodide in the presence of hexamethylphosphoric triamide afforded the corresponding methyl ethers. The reaction of 3-ethynyl-5-isopropenyl-3-methoxy-2-methylcyclohexene with butyllithium and trichloro(vinyl)silane yielded optically active dichlorosilyl-containing acetylenic compounds.     

The Synthesis of (±)-11-Deoxydaunomycinone via Regioselective Tandem Diels-Alder Reactions

The 2,5-dimethylidene-3,6-bis[(Z)-(2-nitrophenyl)sulfenylmethylidene]-7-oxabicyclo[2.2.1]heptane ( 13 ) can be used to generate polyfunctional and multicyclic molecules with high regio- and stereoselectivity via two successive Diels-Alder additions using two different dienophiles. This principle has been applied to the synthesis of (±)-11-deoxydaunomycinone ( 7 ), the aglycone of an important antitumor drug. The 2,3-didehydroanisole adds to 13 and gives the monoadduct 14 with high regioselectivity. No trace of bis-adduct is observed. The 1,4-epoxy-1,2,3,4-tetrahydro-5-methoxy-3-methylidene-2-[(Z)-(2-nitrophenyl)sulfenylmethylidene]anthracene ( 15 ) obtained on treating 14 with K₂CO₃ adds to methyl vinyl ketone to give [(1RS, 2SR, 5RS,12RS)-5,12-epoxy-1,2,3,4,5,12-hexahydro-7-methoxy-1-(2-nitrophenyl)sulfenyl-2-naphthacenyl]methyl ketone ( 16 ) with high regio- and stereoselectivity. The acid-catalyzed 7-oxanorbornadiene→phenol rearrangement of 16 is regioselective and gives (5-acetoxy-3,4-dihydro-7-methoxy-2-naphthacenyl) methyl ketone ( 20 ) which was transformed into (±)-7,11-dideoxydaunomycinone ((±)- 24 ), a known precursor of 7 .     

Synthesis of Methyl 5(6)-(4-Aminophenoxy)- and 5(6)-(2-Aminophenoxy)-2-benzimidazolyl Carbamates and Their Biological Properties

A procedure was developed for preparation of methyl 5(6)-(4-aminophenoxy)- and 5(6)-(2-aminophenoxy)-2-benzimidazolyl carbamates by reaction of 3,4,4`-triaminodiphenyl or 3,4,2`-triaminodiphenyl ethers respectively with methyl cyanocarbamate in water solution in the presence of 7-10 molar excess of acetic acid. The helminthicidal properties, embryotoxicity, and overall toxicity of compounds obtained were estimated.     

Synthesis of new functionally substituted hetarylcarbamates from methyl {4-[(2<Emphasis Type="Italic">E</Emphasis>)-3-(4-methoxyphenyl)-prop-2-enoyl]phenyl}carbamate

Three-component condensation of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl}- carbamate with ninhydrin and L-proline in methanol–water (10: 1) afforded methyl {4-[1,3-dioxo-1′- (4-methoxyphenyl)-1,1′,2′,3,5′,6′,7′,7a′-octahydrospiro[indene-2,3′-pyrrolizin]-2′-ylcarbonyl]phenyl}carbamate. Heating of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl}carbamate with isatin and benzylamine in methanol gave methyl {4-[4′-(4-methoxyphenyl)-2-oxo-5′-phenyl-1,2-dihydrospiro[indole-3,2′-pyrrolidin]-3′-ylcarbonyl]phenyl}carbamate. The condensation of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2- enoyl]phenyl}carbamate with sarcosine and 11H-indeno[1,2-b]quinoxalin-11-one generated in situ from ninhydrin and o-phenylenediamine in boiling ethanol led to the formation of methyl {4-[4′-(4-methoxyphenyl)-1′-methyl-11,11a-dihydro-5aH-spiro[benzo[b]phenazine-6,2′-pyrrolidin]-3′-ylcarbonyl]phenyl}carbamate.     

Synthesis and tautomerism of 2-[3(5)-aryl(methyl)pyrazol-4-yl]-1-benzimidazoles

An efficient method has been developed for the synthesis of 2-[3(5)-aryl(methyl)pyrazol-4-yl]-1H-benzimidazoles by cyclocondensation of 2-acylmethyl-1H-benzimidazoles benzoylhydrazones with DMF dimethylacetal. The tautomerism of the compounds obtained via migrations of a proton between the pyrazole nitrogen atoms has been studied by ¹H NMR. The more stable tautomers have electron acceptor aryl substituents placed at position 3 of the pyrazole ring and electron donor aryl substituents or a methyl at position 5. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1370–1377, September, 2006.     

One-Pot Three-Component Synthesis of a Series of 2-Amino-4-(4-oxo-4H-chromen-3-yl)-5-(2,2,2-trifluoroacetyl)-6-(trifluoromethyl)-4H-pyrans and 2-Amino-4-(4-oxo-4H-chromen-3-yl)-5-(thiophene-2-carbonyl)-6-(trifluoromethyl)-4H-pyrans as Promising Anticancer Agents

Russian Journal of Organic Chemistry - Novel functionalized 2-amino-4-(4-oxo-4H-chromen-3-yl)-5-(2,2,2-trifluoroacetyl)-6-(trifluoro­methyl)-4H-pyrans and...     

Reactions of 5-[3-(trifluoromethyl)-phenyl]furan-2-carbaldehyde

The Knoevenagel condensations of 5-[3-(trifluoromethyl)phenyl]furan-2-carbaldehyde with seven compounds containing an active methyl or methylene group have been studied. The compounds used were: methyl 2-cyanoacetate, malononitrile, 2-furylacetonitrile, acetophenone, 2-thioxo-1,3-thiazolidin-4-one (rhodanine), 5,5-dimethylcyclohexane-1,3-dione (dimedone), and methyl 2-azidoacetate. The effect of microwave irradiation on the condensation reactions was studied and compared with “’classical”’ conditions. Thermolysis of methyl 2-azido-3-{5-[3-(trifluoromethyl)phenyl]-2-furyl}propenoate afforded methyl 2-[3-(trifluoromethyl)phenyl)]-4H-furo[3,2-b]pyrrole-5-carboxylate. (2E)-3-{ 5-[3-(Trifluoromethyl)phenyl]-2-furyl}propenoic acid was converted to the corresponding azide, which was cyclized on heating into 2-[3-(trifluoromethyl)phenyl)]-4,5-dihydrofuro[3,2-c]pyridin-4-one. The latter after successive action of POCl₃ and NH₂NH₂-Pd/C gave 2-[3-(trifluoromethyl)-phenyl]furo[3,2-c]pyridine. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 825–831, June, 2006.     

Experimental and Computational Investigations of 4-((E)-(2-Amino-5- Nitrophenylimino)Methyl)-5- (Hydroxymethyl)-2-Methylpyridin-3-Ol Schiff Base Derived from Vitamin B<Subscript>6</Subscript>

An unsymmetrical tridentate Schiff base 4-((E)-(2-amino-5-nitrophenylimino)methyl)-5-(hydroxymethyl)- 2-methylpyridin-3-ol is newly synthesized and characterized experimentally. Its geometrical parameters, the assignment of IR bands and NMR chemical shifts are also computed by the density functional theory (DFT) method. In addition, the atoms in molecules (AIM) analysisis employed to investigate its geometry. Only one of the diamine–NH₂ groups undergoes the condensation reaction. In the structure of the synthesized Schiff base, the remaining aminogroup lies in the para position with respect to the nitro group (isomer 1). In both gas and solution phases, isomer 1 is more stable than isomer 2 with the meta orientation of the amino and nitro groups. The NMR chemical shifts and the AIM analysis show that isomer 1 is a more favorite structure for the synthesized Schiff base. It has no planar structure. The phenolic proton is engaged in the intramolecular hydrogen bond with the azomethine nitrogen atom. The experimental results are in good agreement with the theoretical ones, confirming the validity of the optimized geometry.     

Synthesis and anticancer activity evaluation of (<Emphasis Type="Italic">E</Emphasis>)-3-{[5-(aryl)-1,3,4-oxadiazol-2-yl]methyl}-5-(3,4,5-trimethoxybenzylidene)thiazolidine-2,4-diones

A series of new substituted (E)-3-{[5-(aryl)-1,3,4-oxadiazol-2-yl]methyl}-5-(3,4,5-trimethoxy-benzylidene) thiazolidine-2,4-diones have been synthesized. The products have been characterized by their IR, ¹H NMR, ¹³C NMR, and mass spectral properties and evaluated for anticancer activity against four human cancer cell lines: A549, A375, MCF-7, and HT-29.     

A novel synthesis of (2S)-3-(2,4,5-trifluorophenyl)propane-1,2-diol by sharpless asymmetric epoxidation method

Synthesis of (2S)-3-(2,4,5-trifluorophenyl)propane-1,2-diol by the Sharpless asymmetric epoxidation reaction has been achieved. 2,4,5-Trifluorobenzaldehyde with methyl 2-(triphenyl-λ⁵-phosphanylidene)acetate gave methyl (E)-3-(2,4,5-trifluorophenyl)acrylate in 83% yield. The reduction of ester group with DibalH followed by Sharpless asymmetric epoxidation gave ((2R,3R)-3-(2,4,5-trifluorophenyl)oxiran-2-yl)methanol. Pd/C-catalyzed hydrogenation of epoxy alcohol furnished (2S)-3-(2,4,5-trifluorophenyl)propane-1,2-diol with >90% ee and 71% yield.     

Heterocyclizations of 1-(Benzothiazol-2-yl)-4-phenylthiosemicarbazide

1-(Benzothiazol-2-yl)-4-phenylthiosemicarbazide reacted with methyl iodide in the presence of sodium acetate in boiling ethanol to give 2,2′-dithiobis[N-(5-methylsulfanyl-4-phenyl-4H-1,2,4-triazol-3-yl)-benzenamine]. The reaction of the title compound with dimethyl acetylenedicarboxylate in dioxane led to the formation of methyl 3-(benzothiazol-2-yl)-2-(2-methoxy-2-oxoethyl)-2,3-dihydro-1,3,4-thiadiazole-2-carboxylate.     

The reaction of (4R,5R)- and (4S,5S)-4,5-epoxy-2(E)-hexenoates and secondary amines.

A reaction of methyl (4R,5R)-4,5-epoxy-2(E)-hexenoate 1 with N-benzylmethylamine gave a diastereomerically pure methyl (4R,5R)-4,5-epoxy-(3S)-N-benzylmethylamino hexanoate 6 and methyl (4S,5R)-4-N-benzyl-methylamino-5-hydroxy-2(E)-hexenoate 7. The former was chemoenzymatically converted to (-)-osmundalactone 11, which is an aglycone of osmundalin. On the other hand, the directly conjugated addition of dimethylamine to methyl (4S,5S)-4,5-epoxy-2(E)-hexenoate 1 followed by treatment with MeOH at 40 degrees C exclusively provided methyl (4R,5S)-4-dimethylamino-5-hydroxy-2(E)-hexenoate 16, which was converted into L-(-)-forosamine 18.     

Aqueous hydrolysis of 3-[2-(3-methyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-yl)-ethylamino]-and 3-[2-(5-methyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-yl)ethylamino]-propanoates

Noncatalytic hydrolysis of methyl 3-[2-(3-methyl-1H-pyrazol-1-y)ethylamino]-and methyl 3-[2-(5-methyl-1H-pyrazol-1-yl)ethylamino]propanoates at 200°C was performed. According to X-ray diffraction data, the resulting acids exist exclusively as salts.     

Synthesis 5-(pyrazolin-3-ylmethylidene)-2-thiohydantoins and 2-alkylsulfanyl-5-(pyrazolin-3-ylmethylidene)-3,5-dihydro-4<Emphasis Type="Italic">H</Emphasis>-imidazol-4-ones

A reaction of 3-allyl- and 3-phenylthiohydantoins with 1,5-diphenyl- and 1-phenyl-substituted 3-formyl-2-pyrazolines was used to obtain a series of 5-(pyrazolin-3-ylmethylidene)-2-thioxotetrahydro-4H-imidazol-4-ones, the subsequent alkylation of which with methyl iodide or ethyl chloroacetate gave the corresponding 2-alkylthio-5-(pyrazolin-3-ylmethylidene)-3,5-dihydro-4H-imidazol-4-ones in the yields from 30 to 77%. The oxidation of (5Z)-3-phenyl-5-[(1,5-diphenylpyrazolin-3-yl)methylidene]-2-methylsulfanyl-4,5-dihydroimidazol-4-one with lead tetraacetate led to the corresponding pyrazole in 48% yield.