Synthesis of Fused Compounds on the Basis of Chalcogen Chlorides and 2-Allylphenols

Efficient methods have been developed for regioselective synthesis of new organochalcogen compounds containing 2,3-dihydro-1-benzofuran-2-ylmethyl and 7-methyl-2,3-dihydro-1-benzofuran-2-ylmethyl substituents by reactions of selenium and sulfur dichlorides and tellurium tetrachloride with 2-allylphenol and 2-allyl-6-methylphenol.     

Functionalization of methyl 3-acetyl-5-[(methoxycarbonyl)amino]-2-methyl-1<Emphasis Type="Italic">H</Emphasis>-indole-1-carboxylate

Oxidative heterocyclization of methyl 3-{1-[2-(carbamoylhydrazinylidene)]ethyl}-2-methyl-5-[(methoxycarbonyl)amino]-1H-indole-1-carboxylate by the action of selenium dioxide in acetic acid and heating of the corresponding thiosemicarbazone in boiling acetic anhydride gave 1,2,3-selenadiazole and 2,3-dihydro-1,3,4-thiadiazole derivatives, respectively. Methyl 3-acetyl-2-methyl-5-[(methoxycarbonyl)amino]-1H-indole-1-carboxylate reacted with selenium dioxide in dioxane–water (30: 1) at 80?90°C to form methyl 5-[(methoxycarbonyl)amino]-2-methyl-3-(2-oxoacetyl)-1H-indole-1-carboxylate whose condensation with o-phenylenediamine afforded methyl 2-methyl-5-[(methoxycarbonyl)amino]-3-(quinoxalin-2-yl)-1H-indole-1-carboxylate.     

Reaction of Dimethyl Sulfoxide with 4-Acyloxycoumarins

Dimethyl sulfoxide converts 4-acetoxycoumarin (1) exclusively to 2-(2-hydroxybenzoyl)-2-[(methylthio)methyl]-2,3-dihydro-4 H-furo[3,2-c]chromen-4-one (3) at 180°C under a nitrogen atmosphere, but in the absence of nitrogen, the products obtained are dicoumarol and its dehydrative cyclization products 7 H-bis[1]benzopyrano[4,3-b: 3′,4′-c]pyran-6,8-dione (9) and (3). Under similar conditions, 4-benzoyloxycoumarin (1a) affords benzoic acid, 4-hydroxy-3-({2-[(methylthio)methyl]-3-oxo-2,3-dihydro-1-benzofuran-2-yl}methyl)-2H-chromen-2-one (7), and 3-(2-hydroxybenzoyl)-3,4-dihydro-2H,5H-pyrano[2,3-b] chromen-5-one (8).     

Rhenium tricarbonyl core complexes of thymidine and uridine derivatives

Thymidine and uridine were modified at the C2' and C5' ribose positions to form amine analogues of the nucleosides (1 and 4). Direct amination with NaBH(OAc)3 in DCE with the appropriate aldehydes yielded 1-{5-[(bis(pyridin-2-ylmethyl)amino)methyl]-4-hydroxytetrahydrofuran-2-yl}-5-methyl-1H-pyrimidine-2,4-dione (L1), 1-{5-[(bis(quinolin-2-ylmethyl)amino)methyl]-4-hydroxytetrahydrofuran-2-yl}-5-methyl-1H-pyrimidine-2,4-dione (L2), and 1-[3-(bis(pyridin-2-ylmethyl)amino)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-pyrimidine-2,4-dione (L5), while standard coupling procedures of 1 and 4 with 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid (2) and 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid (3) in the presence of HOBT-EDCI in DMF provided a second novel series of bifunctional chelators: 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid [(3-hydroxy-5-(5-methyl-4-oxo-3,4-dihydro-2H-pyrimidin-1-yl)tetrahydrofuran-2-yl)methyl] amide (L3), 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid [(3-hydroxy-5-(5-methyl-4-oxo-3,4-dihydro-2H-pyrimidin-1-yl)tetrahydrofuran-2-yl)methyl] amide (L4), 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid [2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-3-yl] amide (L6), and 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid [2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-3-yl] amide (L7). The rhenium tricarbonyl complexes of L1-L4, L6, and L7, [Re(CO)3(LX)]Br (X=1-4, 6, 7: compounds 5-10, respectively), have been prepared by reacting the appropriate ligand with [NEt4][Re(CO)3Br3] in methanol. The ligands and their rhenium complexes were obtained in good yields and characterized by common spectroscopic techniques including 1D and 2D NMR, HRMS, IR, cyclic voltammetry, UV, and luminescence spectroscopy and X-ray crystallography. The crystal structure of complex 6.0.5NaPF6 displays a facial geometry of the carbonyl ligands. The nitrogen donors of the tridentate ligand complete the distorted octahedral spheres of the complex. Crystal data: monoclinic, C2, a = 24.618(3) A, b = 11.4787(11) A, c = 15.5902(15) A, beta = 112.422(4) degrees , Z = 4, D(calc) = 1.562 g/cm3.     

An expedient cyclization of polyfunctional (aryl)(pyrimidinyl)(pyranyl)methanes into spiro[furo[3,2-c]pyran-2,5’-pyrimidine] scaffold

Spirocyclization of morpholinium 3-[(aryl)(1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl)methyl]-6-methyl-2-oxo-2H-pyran-4-olate by the action of sodium acetate-N-bromosuccinimide system in ethanol at room temperature results in spiro[furo[3,2-c]pyran-2,5’-pyrimidine] derivatives in 92–98% yields, the protocol allowing to avoid column chromatography purification. This new highly efficient and facile procedure is a convenient way to substituted unsymmetrical spiro scaffold containing pyrimidine-2,4,6-trione and 2,3-dihydro-4H-furo[3,2-c]pyran-4-one fragments promising for biomedical applications.     

Unexpected course of rearrangement of substituted S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides

Three series of S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides differing in substitution at the isothiuronium moiety (none, one or two methyl groups) and at the benzene ring were prepared and characterized. These salts were then treated with various bases (acetate, triethylamine, Na₂CO₃) to give either 1-hydroxy-3-oxo-1,3-dihydro-2H-isoindol-2-carbothioamides or the product of S to N isobenzofuranone-3-yl migration, i.e., 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas. If ammonia was used in reaction with N,N′-dimethyl isothiuronium salts then 3-hydroxy-2,3-dihydro-1H-isoindol-1-ones were formed together with 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas in parallel reaction with the yields increasing with ammonia concentration. The formation of isoindolones takes place in two steps with an aldehyde intermediate, which can be trapped with N,N-dimethylhydrazine.     

Condensed diazepines. synthesis of 1-aryl-3,5-dihydro-4H-1-benzofuro-[2,3-<Emphasis Type="Italic">d</Emphasis>][1,2]diazepin-4-ones

The cyclocondensation of (2-aroyl-1-benzofuran-3-yl)acetic acids and their methyl esters with hydrazine hydrate under various experimental conditions has been studied. Optimal conditions have been found for obtaining 1-aryl-3,5-dihydro-4H-1-benzofuro[2,3-d][1,2]diazepin-4-ones.     

Molecular structures of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-5-carboxylate and methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-3-carboxylate

The structure of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-5-carboxylate is determined by X-ray crystallography and further used to elucidate the structure of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-3-carboxylate, using the data of homo- and heteronuclear 2D NMR correlation spectroscopy.     

Ruthenium-mediated cycloaromatization of acyclic enediynes and dienynes at ambient temperature

The ruthenium(II) cation, [Cp*Ru(NCMe)3]OTf (4), triggers the Bergman cycloaromatization of acyclic endiynes at room temperature in THF solvent. Treatment of 1,2-di(1-alkynynyl)cyclopentenes (13-Me, alkynyl = propynyl; 13-Prn, alkynyl = pentynyl; 13-Bui, alkynyl = 4-methyl-pent-1-ynyl) with 4 in THF solvent at room temperature gives rise to the ruthenium arene complexes: [Cp*Ru{(3a,4,5,6,7,7a-eta)-2,3-dihydro-5,6-dialkyl-1H-indene}]OTf (15-Me, alkyl = methyl, 64% yield; 15-Prn, alkyl = n-propyl, 73% yield; 15-Bui, alkyl = 4-methyl-1-pentynyl, 88% yield). In a similar fashion, the room-temperature reaction of 4 with 1-ethynyl-2-(1-propynyl)cyclopentene (11) and [2-(1-propynyl)-1-cyclopenten-1-yl]trimethylsilane (14) leads to the formation of [Cp*Ru{(3a,4,5,6,7,7a-eta)-2,3-dihydro-5-methyl-1H-indene}]OTf (12, 92% yield) and [Cp*Ru{(3a,4,5,6,7,7a-eta)-2,3-dihydro-6-methyl-1H-inden-5-yl)trimethylsilane}]OTf (16, 77% yield), respectively. The bis(TMS)-substituted enediyne (1-cyclopentene-1,2-diyldi-2,1-ethynediyl)bis(trimethylsilane) (9-TMS) and 4 underwent reaction at 100 degrees C to give [Cp*Ru{(3a,4,5,6,7,7a-eta)-2,3-dihydro-1H-inden-5-yl)trimethylsilane}]OTf (10, 69% yield). Deuterium-labeling studies rule out a mechanism that involves a ruthenium-vinylidene intermediate, and provide support for the involvement of a p-benzyne intermediate. In a similar fashion, complex 4 is shown to trigger the cycloaromatization of the conjugated dienyne, 1-ethenyl-2-(1-pentynyl)cyclopentene (19), at room temperature in chloroform-d1 solvent to give [Cp*Ru{(3a,4,5,6,7,7a-eta)-2,3-dihydro-5-(1-propyl)-1H-indene}]OTf (20, 96% yield), with no deuterium enrichment. In the absence of ruthenium the thermal cyclization reactions of unsubstituted acyclic enediynes (Bergman cycloaromatization) and acyclic conjugated dienynes (Hopf cyclization) typically require elevated temperatures (150-250 degrees C). Complexes 10 and 15-Prn were characterized structurally by X-ray crystallography.     

Reactions of Hydrazonoyl Halides 33 1 : Synthesis of Some New 2,3-Dihydro-1,3,4-thiadiazoles Containing Pyrazol-3-yl,Indolin-2-one-2-yl and Indan-1,3-dione-2-yl Moieties

Some new 2,3-dihydro-1,3,4-thiadiazoles containing pyrazol-3-yl, indolin-2-one-2-yl and indan-1,3-dione-2-yl moieties in a good yields obtained from the reaction of hydrazonoyl halides with thiocarbamate and carbodithioate in ethanolic triethylamine respectively. In contrast, pyrazolylthiourea reacts with hydrazonoyl halides under the same condition afford corresponding hydrazonoyl sulfide derivatives.     

Synthesis of 3-pyrrol-3′-yloxindoles with a carbamate function

By the reaction of methyl {4(3)-[2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)acetyl]phenyl} carbamates with ethyl 3-aminocrotonate at boiling in the mixture toluene-anhydrous ethanol, 2: 1, ethyl 5-{3(4)-[(methoxycarbonyl)amino]phenyl}-2-methyl-4-(2-oxo-2,3-dihydro-1H-indol-3-yl)-1H-pyrrole-3-carboxylates were obtained. The condensation of methyl {3(4)-[2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)acetyl] phenyl}carbamates with ethyl acetoacetate in the presence of ammonium acetate and 20 mol% of 1-methyl-3-butylimidazolium chloride or 1-methyl-3-octylimidazolium tetrafluoroborate at boiling in anhydrous ethanol led to the formation of the corresponding 3-pyrrol-3′-yloxindoles with a carbamate function.     

Reactions of chloromethyloxirane and dihalopropanols with chalcogens in basic reducing systems

Chloromethyloxirane and 2,3-dibromopropan-1-ol reacted with a solution of selenium or tellurium in the system hydrazin hydrate-potassium hydroxide (K₂Se₂, K₂Te₂) to give allyl alcohol; the reaction was accompanied by regeneration of the initial free chalcogen. 1,3-Dichloropropan-2-ol reacted with selenium in the same system to give oligomeric product having a 2-hydroxypropane-1,3-diyldiseleno monomeric unit, while the reaction with tellurium led to the formation of allyl alcohol and almost complete regeneration of initial tellurium. Probable reaction mechanisms are discussed. Polyselenide oligomers containing a hydroxy group in a monomeric unit were formed in reactions of chloromethyloxirane and 1,3-dichloropropan-2-ol with selenium in the system hydrazine hydrate-2-aminoethanol. Under analogous conditions 2,3-dibromopropan-1-ol was converted into allyl alcohol with regeneration of elemental selenium. Reductive cleavage of polyselenide oligomers gave Se-methyl derivatives of 2-hydroxypropane-1,3-diselenol.     

Reactions of 2,3-dichloro-1-propene with sulfur and tellurium in the system hydrazine hydrate-KOH

2,3-Dichloro-1-propene reacts with sulfur dissolved in the system hydrazine hydrate-KOH (with formation of K₂S₂ or K₂S) to afford bis(2-chloro-1-propene-3-yl)sulfide as the main product in both cases. Under similar conditions tellurium induces β-elimination of both chlorine atoms resulting in the formation of allene and complete regeneration of tellurium metal.     

Synthesis and Transformations of 5-Substituted 2-Aryl-7H-[1,2,4]triazolo[3,2-b][1,3]thiazin-7-ones and 2-Aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones

3-Aryl-1,2,4-triazole-5-thiones react with dimethyl acetylenedicarboxylate and methyl 3-phenyl-propynoate to afford the corresponding 5-substituted 2-aryl-7H-[1,2,4]triazolo[3,2-b][1,3]thiazin-7-ones. Treatment of 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones with alkalies leads to formation of 3-(benzimidazol-2-ylsulfanyl)-3-arylpropionic acids, their reaction with methyl p-toluenesulfonate yields 1-(3-methyl-2-thioxo-2,3-dihydro-1N-benzimidazol-1-yl)-3-phenyl-2-propen-1-one, and oxidation with hydrogen peroxide gives benzimidazole-2-sulfonic acid and 3-aryl-2-propenoic acids.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005, pp. 109–114.Original Russian Text Copyright © 2005 by Britsun, Esipenko, Chernega, Lozinskii.     

Synthesis of Some New Thieno[2,3-b]pyridines,Pyrimidino[4′,5′:4,5]thieno[2,3-b]-pyridines,and 2,3-Dihydro-1,3,4-thiadiazoles

Thieno[2,3-b]pyridines were synthesized from 6-benzofuran-2-yl-4-phenyl-2-sulfanylpyridine-3-carbonitrile and each of chloro acetone, ethyl chloroacetate, ω -bromoacetophenone, and chloroacetonitrile. These compounds were conveniently converted into novel pyrido[4′,5′:4,5]thieno[3,2-d]pyrimidines. Also, 2,3-dihydro-1,3,4-thiadiazole was synthesized from hydrazonoyl halides and 2-benzofuran-2-yl-3-(phenylamino)-3-thioxopropanenitrile. The structures of the products have been elucidated by elemental analyses, spectral data studies, and alternative syntheses whenever possible. The newly synthesized compounds were tested towards microorganisms.     

Copper(II) complexes containing chiral substituted 2-(4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one-2-yl)pyridine ligands: Synthesis, X-ray structural studies and asymmetric catalysis

New chiral N,N-bidentate ligands derived from substituted 2-(4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one-2-yl)pyridines have been prepared and characterised by means of ¹H, ¹³C NMR spectroscopy and optical rotation. Their Cu(II) complexes were characterized by means of elemental analysis, ¹H NMR spectroscopy and MS. By means of X-ray diffraction, molecular geometry of the complex of 2-(1-methyl-4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one-2-yl)pyridine with copper(II) chloride was determined. The complex exhibits heterochiral dimeric arrangement of two square pyramids with one terminal and one bridge-forming chlorine atoms and two nitrogen atoms in the bases of the pyramids. The tops of these pyramids are formed by the remaining chlorine atoms. The complexes prepared catalyse the Henry reaction with the overall yields of 41-97% and with the maximum enantioselective excess of 19%.     

Synthesis via pummerer intermediates. III. Rearrangements of 3-(methylsulfinyl)quinolinones, 3-(methylsulfinyl)cinnolinones, 3-(methylsulfinyl)chromanones and 3-(methylsulfinyl)chromones with acetic anhydride and with thionyl chloride

The reaction of 1-methyl-3-(methylsulfinyl)-4(1H)quinolinone ( 1 ) with acetic anhydride and thionyl chloride gave 3-[[(acetyloxy)methyl]thio]]-1-methyl-4(1H)quinolinone ( 2 ) and 3-[(chloromethyl)thio]-1-methyl-4(1H)quinolinone ( 3 ) respectively. 3-(Methylsulfinyl)-4(1H)cinnolinone ( 4 ) gave the corresponding products when treated under similar conditions. Treatment of 8-methoxy-3-(methylsulfinyl)-4H-1-benzopyran-4-one ( 11 ) with acetic anhydride and thionyl chloride gave bis addition vinyl Pummerer products 2,3-bis(acetyloxy)-2,3-dihydro-8-methoxy-3-(methylthio)-4H-1-benzopyran-4-one ( 12 ) and 2,3-dichloro-2,3-dihydro-8-methoxy-3-(methylthio)-4H-1-benzopyran-4-one ( 13 ), respectively.     

A novel series of 2,5-disubstituted 1,3,4-thiadiazoles as potential anticonvulsant agent

<正>In pursuit for better antiepileptic drug and the importance of semicarbazones and 2,5-disubstituted 1,3,4-thiadiazoles as anticonvulsant pharmacophore,a series of novel N-({5-[(6-methyl-1-benzofuran-3-y1)methyl]-1,3,4-thiadiazol-2-yl}carbamothioyl) -2/3/4-substitutedbenzamide were designed,synthesized and evaluated for their anticonvulsant activity.The findings of the present studies confirmed that the pharmacophore model with four binding sites is crucial for anticonvulsant activity. Structure-activity relationships among synthesized compounds were also established.     

Asymmetric palladium-catalyzed annulation of benzene-1,2-diol and racemic secondary propargylic carbonates bearing two different substituents

The palladium-catalyzed cyclization of benzene-1,2-diol with various racemic secondary propargyl carbonates having no acetylenic hydrogen in the presence of (R)-Binap as the chiral ligand afforded the two regioisomers of the corresponding 2,3-dihydro-1,4-dioxin derivatives in quite good yields, and also in enantioselectivities going from 40 to 97%. The cyclization of benzene-1,2-diol with methyl (R)-1-methyl-3-phenylpro-2-yn-1-yl carbonate in the presence of dppb as the achiral ligand afforded 2-benzylidene-3-methyl-2,3-dihydro-1,4-benzodioxine as the major product with 15% ee. The use of (R)-Binap as the chiral ligand afforded the (+) cyclized compound in 45% ee, when the (−) enantiomer was obtained with 77% ee in the presence of (S)-Binap. All the results suggest that in this case the enantioselective step is the diastereoselective protonation of the palladium-carbene intermediates.     

Mass spectra of new functionally substituted heterocycles: VI. Fragmentation of 3-methoxy-7-methyl-2-methylsulfanyl-4,5-dihydro-3H-azepine, its structural isomers, 5-methoxy-2,2-dimethyl-6-methylsulfanyl-2,3-dihydropyridine and 1-isopropyl-3-methoxy-2-methylsulfanyl-1H-pyrrole, and their linear precursors under electron impact

Mass spectra of previously unknown isomeric 1-isopropyl-3-methoxy-2-methylsulfanylpyrrole, 5-methoxy-2,2-dimethyl-6-methylsulfanyl-2,3-dihydropyridine, and 3-methoxy-7-methyl-2-methylsulfanyl-4,5-dihydro-3H-azepine were studied for the first time. Fragmentation of all heterocyclic compounds under electron impact begins with elimination of methyl radical, and the subsequent decomposition of the [M ? Me]⁺ ion (m/z 170) is specific for each isomers, which ensures their reliable identification in reaction mixtures. The corresponding linear precursors, methyl N-isopropyl-2-methoxybuta-2,3-dienimidothioate and 2-methoxy-N-(1-methylethylidene)-1-methylsulfanylbuta-1,3-dien-1-amine undergo isomerization and decomposition even under very mild temperature conditions, so that their mass spectra could not be recorded.