Synthesis of new pyridazino[4′,3′:4,5]-thieno[3,2-d]-1,2,3-triazine and pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine derivatives

Summary 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-one (2), 3-substituted 8,9-diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-ones (3a–c), 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-one (4), 8-chloro-3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazine (5), 8-substituted 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazines (6a–h) and 7-substituted 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-ones(7a–c) were synthesized from 5-amino-3,4-diphenylthieno[2,3-c]pyridazine-6-carboxamide (1).

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Synthese neuer Pyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-und Pyrimido[4,5:4,5]thieno[2,3-c]pyridazin-Derivate

Zusammenfassung Folgende Verbindungen wurden ausgehend von 5-Amino-3,4-diphenylthieno[2,3-c]pyridazin-6-carboxamid (1) synthetisiert: 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-on (2), 3-substituierte 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-one (3a–c), 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8[7H]-on (4), 8-Chlor-3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin (5), 8-substituierte 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazine (6a–h) und 7-substituierte 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-one (7a–c).

     

Synthesis and functionalization oftrans-2-(2′-aminocyclohexyloxy)-andtrans-2-(2′-azidocyclohexyloxy)acetic acid

Summary Synthesis of the hydrochloride oftrans-2-(2-aminocyclohexyloxy)acetic acid (4) fromtrans-2-(2-azidocyclohexyloxy)acetic acid (1) is described.4 was acylated at the amino group to give compounds5–8.1 was converted into acid chloride (9) and amides10–13.

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Synthese und Funktionalisierung dertrans-2-(2-Aminocyclohexyloxy)- undtrans-2-(2-Azidocyclohexyloxy)essigsäure

Zusammenfassung Die Synthese destrans-2-(2-Aminocyclohexyloxy)essigsäurehydrochlorids (4), ausgehend vontrans-2-(2-Azidocyclohexyloxy)essigsäure (1), wird beschrieben.4 wurde durch Acylierung der Aminogruppe in die Verbindungen5–8 übergeführt.1 wurde in das Säurechlorid9 und die Carbonsäureamide10–13 umgewandelt.

     

Synthesis of 4,4′-bis(4-aminophenoxy)benzophenone and polyimides based on this compound

Synthesis of 4,4-bis(4-aminophenoxy)benzophenone was performed starting from chloral. Various polyimides were obtained by reactions of 4,4 -bis(4-aminophenoxy)benzophenone with aromatic tetracarboxylic acid dianhydrides. Some of the polyimides obtained are crystalline compounds.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 673–676, March, 1996.     

Reaction of 2-methyl-4,5-dihydrofuran with hydrogen chloride

Reaction of 2-methyl-4,5-dihydrofuran with HCl at 0°C yields 5-chloro-2-pentanone (13%) and 1-(2-methyltetrahydrofuryl-2)-5-chloro-2-pentanone (27%) and at 200° 5-chloro-2-pentanone exclusively.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. I. M. Gubkin State Petroleum and Gas Academy, 117917 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 9, pp. 2188–2191, September, 1992.     

Diastereomeric Oxathia[n](1,1′)ferrocenophanes

Zusammenfassung Neue Oxathiaferrocenophane wurden durch Umsetzung von 1,1-Bis(hydroxymethyl)ferrocen mit Dithiolen dargestellt, welche Sauerstoff in den Alkylketten enthalten. Die Reaktion von 1,1-Bis(-hydroxyethyl)ferrocenen mit Dithiolen führte zu Mischungen von Diastereomeren, aus welchen reine Stereoisomere isoliert und charakterisiert wurden. Einige Aspekte des stereochemischen Verlaufes dieser Reaktionen werden diskutiert.

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Diastereomere oxathia[n](1,1)ferrocenophane

Novel oxathiaferrocenophanes have been synthesized by the reaction of 1,1-bis(hydroxymethyl)ferrocene with dithiols bearing oxygen in chains. The reactions of 1,1-bis(-hydroxyethyl)ferrocenes with dithiols afforded mixtures of diastereomeric products from which pure stereoisomers were isolated and characterized. Some aspects concerning a stereochemical course of the reactions described are discussed.

     

Synthesis and crystal structure ofN,N′-DicyclohexylpiperazineN,N′-dioxide octahydrate

N,N-DicyclohexylpiperazineN,N-dioxide octahydrate, C₁₆H₄₆N₂O₁₀,M _r=426.55, monoclinic, space groupC2/m (No. 12),a=12.961(4),b=11.533(4),c=7.907(1) Å, =98.37(2)^o,V=1169.3(6) ų,Z=2. The structure was solved by the direct method and refined toR=0.045 for 1192 observed MoK reflections. TheN,N-dioxide molecule occupies a site of symmetry 2/m. The piperazine ring takes the chair form with the two N–O bonds oriented axially in atrans configuration. Hydrogen bonding between the water molecules, as well as between theN-oxide groups and water molecules, gives rise to a puckered layer composed of edge-sharing four-membered, five-membered, six-membered, and eight-membered rings. Adjacent layers are cross-linked by theN,N-dicyclohexylpiperazine moieties lying between them, thereby generating a sandwich structure consolidated by covalent and hydrogen bonding. Supplementary Data relating to this article are deposited with the British Library as Supplementary Publication No. SUP 82062 (8 pages).     

α-Cyclopropylalkyl cations of a spiro[2.4] heptane system

-Cyclopropylalkyl cations of a spiro[2.4]heptane system, which are possible intermediates in solvolytic reactions of the corresponding cyclopropylalkanol derivatives, have been generated from compounds of the spiro(indan-2,1-cyclopropane), spiro(indan-1,1-cyclo-propane), and spiro[acenaphthylene-1(2H),1-cyclopropane] classes under long life conditions (HSO{in3}F-SO{in2}FCl-CD{in2}Cl{in2}, –100 °C).Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2194–2198, December, 1994.This work was carried out with the financial support of the Russian Foundation for Basic Research (Project No. 93-03-4715).     

Synthesis of new 4,4′-bis(arylethynyl)benzophenones and 4,4′-bis(arylglyoxalyl)benzophenones based on chloral

4,4-Diiodobenzophenone was obtained by a three-stage synthesis from chloral and iodobenzene. 4,4-Bis(arylethynyl)benzophenones were synthesized by cross-coupling of 4,4-diiodobenzophenone with terminal arylethynes in the presence of a complex Pd catalyst; further oxidation of the products obtained in an iodine/DMSO medium afforded new bis(arylglyoxalyl)benzophenones.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 670–672, March, 1996.     

Kraftfeldrechnungen an linearen Oligopyrrolen: 2,2′-Bipyrrol, 2,2′-Furylpyrrol und Prodigiosen

Using a specific force field model, relative stabilities of 2,2-bipyrrole and 2,2-furylpyrrole conformers as well as of prodigiosene tautomers, configurations, and conformations, are studied. 2,2-Bipyrrole adopts anantiperiplanar conformation in accord with other theoretical calculations and experimental findings. Its rotational barrier calculated by this method compares favourably to the one derived by other means. For the parent prodigiosene the (Z)sp,sp arrangement is found to be the most stable one. The two possible tautomers within its dipyrrin fragment do not show a significant energy difference.

     

Room temperature phosphorescence optosensing for gadolinium

An optosensing method for gadolinium based on the room-temperature phosphorescence behavior in aqueous solution induced by the transient adsorption of the complex formed by 1,4-bis (1-phenyl-3-methyl-5-pyrazolone-4-)butanedione (1,4) with Gd (III) on the chelating resin Chelex 100 (packed in a flow cell) is proposed. The proposed optosensing is satisfactory for the determination of the gadolinium ion in the range 8 × 10^–7–5 × 10^–5 M with a correlation coefficient of 0.995. The relative standard deviation was 2.0% for determination of 5× 10^–6 M gadolinium ion (n = 10). The response mechanism of the optosensing and the interferences of other lanthanide ions were also investigated. The method has been used to determine gadolinium ion in synthetic sample.     

Synthesis of some 5′-O-amino acid derivatives of uridine as potential inhibitors ofUDP-glucuronosyltransferase

Summary In an attempt to develop potential inhibitors ofUDP-glucuronosyltransferase, some 5-O-amino acid derivatives of uridine were synthesized. N-protectedL-amino acids were coupled at the 5-O-position of 2,3-O-isopropylideneuridine by esterification employing the method of symmetrical anhydrides in presence of 4-dimethylaminopyridine, 5-O-(N-benzyloxycarbonyl-O-tert.butyl-L-threonl)-23-O-isopropylideneuridine (1), 5-O-(N-tert.butyloxycarbonyl-O-benzyl-L-seryl)-2,3-O-isopropylideneuridine and (2), 5-O-(N-tert.butyloxycarbonyl-L-valyl)-2,3-O-isopropylideneuridine (3), and 5-O-(N-tert.butyloxycarbonyl-L-valyl)-2,3-O-isopropylideneuridine (4) were obtained in good yield after column chromatography on silica gel. The treatment of2 withTFA/CH₂Cl₂ (6:1) at room temperature for 30 min led to a selective removal of theBoc group without deblocking of the 2,3-O-isopropylidene group of uridine. Treatment of2 withTFA/H₂O (5:1) at room temperature for 1 h, however, released bothBoc and 2,3-isopropylidene groups. TheZ group of1 was deprotected by catalytic hydrogenolysis over 10% Pd/C/ammonium formate.

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Synthese von 5-O-Aminosäurederivaten des Uridins als potentielle Inhibitoren derUDP-Glukuronosyl-Transferase

Zusammenfassung In einem Versuch, potentielle Inhibitoren derUDP-Glukuronosyl-Transferase zu entwickeln, wurden einige 5-O-Aminosäurederivate des Uridins synthetisiert. N-GeschützteL-Aminosäuren wurden durch Veresterung mit der 5-O-Position des 2,3-isopropylidenuridins gekuppelt (Methode der symmetrischen Anhydride in der Gegenwart von 5-Dimethylaminopyridin). Solcherweise wurden 5-O-(N-Benzyloxycarbonyl-O-tert.butyl-L-threonly)-2,3-O-isopropylidenuridin (1), 5-O-(N-tert.Butyloxycarbonyl-O-benzyl-L-seryl)-2,3-O-isopropylidenuridin (2), 5-O-(N-tert.Butyloxycarbonyl-L-leucyl)-2,3-O-isopropylidenuridin (3) und 5-O-(N-tert.Butyloxycarbonyl-L-valyl)-2,3-O-isopropylidenuridine (4) nach Säulenchromatographie (Kieselgel) in guter Ausbeute hergestellt. Die Behandlung von2 mitTFA/CH₂Cl₂ (6:1) bei Zimmertemperatur (30 min) führte zu einer selektiven Abspaltung derBoc-Gruppe ohne Deblockierung der 2,3-O-Isopropylidengruppe des Uridins. Eine Behandlung von2 mitTFA/H₂O (5:1) bei Zimmertemperatur für 1 Stunde führte hingegen zur Abspaltung sowohl derBoc als auch der 2,3-O-Isopropylidengruppe. DieZ-Gruppe von1 wurde durch katalytische Hydrogenolyse auf 10% Pd/C/Ammoniumformiat abgespalten.

     

Molecular and crystal structure of 4,5,4′,5′-tetrahydro-2,2′-(1,4-phenylene)bisoxazoline

4,5,4,5-Tetrahydro-2,2-(1,4-phenylene)bisoxazoline, which is one of the most promising stabilizers-consolidators of heterochain polymers, was studied by X-ray structural analysis.Deceased.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2506–2507, October, 1996.     

Transformed steroids

The approaches to the synthesis of various 16,17-disubstituted pregna-4,9-dien-3,20-diones from the corresponding 9-derivatives with labile epoxide, dioxolane, and oxathiolane ringsD have been studied. The transformation has been found to proceed efficiently when the 9-sulfinic esters are used at the intermediate stage and then elimination of sulfinic acid by TsOH/SiO₂ is carried out.For part 193, see ref. 7.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 983–986, May, 1993.     

A general route for the synthesis of pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine derivatives

Summary A facile synthesis of 8-substituted pyrimido[4,5:4,5]thieno[2,3-c]pyridazines (6a–i) has been accomplished. The sequence involves the ring closure of a heterocyclic aminonitrile precursor (3) after reaction with (dichloromethylene)-dimethylammonium chloride.

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Eine allgemeine Synthese von Pyrimido[4,5:4,5]thieno[2,3-c]pyridazin-Derivaten

Zusammenfassung Es wurde ein einfacher Syntheseweg für 8-substituierte Pyrimido[4,5:4,5]thieno-[2,3-c]pyridazine entwickelt. Die Reaktion verläuft über den Ringschluß eines heterocyclischen Aminonitrilvorläufers (3) nach Umsetzung mit Dichlormethylen-dimethylammoniumchlorid.

     

New route for the synthesis of 2-thiouracil analogues of 3′-azido-2′,3′-dideoxy nucleosides

Summary Reaction of 3-azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-D-erythro-pentofuranoside (5) with silylated 2-thiouracil and 5-alkoxy-2-thiouracils in the presence of trimethylsilyl trifluoromethanesulfonate afforded an anomeric mixture of the corresponding 3-azido-2,3-dideoxy-2-thiouridine derivatives with the -anomer as the main product. Deprotected nucleosides were obtained by treatment with tetrabutylammonium fluoride.

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Ein neuer Weg zur Synthese von 2-Thiouracil-Analogen von 3-Azido-2,3-dideoxy-Nucleosiden

Zusammenfassung Die Reaktion von 3-Azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-D-erythro-pentofuranosid (5) mit silyliertem 2-Thiouracil und 5-Alkoxy-2-thiouracil in Gegenwart von Trimethylsilyltrifluormethansulfonat ergab eine anomere Mischung der entsprechenden 3-Azido-2,3-dideoxy-2-thiouridin-Derivate, wobei das -Anomer das Hauptprodukt darstellte. Die ungeschützten Nucleoside wurden mittels Behandlung mit Tetrabutylammoniumfluorid erhalten.

     

New heterocyclic system based on vinylsulfonylfluorobenzene and X-ray structural study of this compound

Oxidation of 1,2,4,5-tetrafluoro-3,6-bus (vinylthio)benzene (1) affords 1,2,4,5-tetra fluoro3,6-bis(vinylsulfonyl)benzene (2) in 65 % yield. The reaction of compound 2 with allylamine gives a new heterocyclic compound, 5,6-difluorobenzo-[a,d]-bis(3,3-dihydro-l,l-sulfonylallyl-4,4-perhydroazine) (3). This compound is the product of nucleophilic addition at the vinylsulfonyl group and intramolecular replacement of fluorine atoms of the benzene ring. The structure of compound 3 has been established by X-ray structural study.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 430–433, February, 1996.     

Synthesis, Spectral and Structural Study of N-[1-(N,N,N′,N′-Tetramethylphosphoramidoyl)- 1H-Benzimidazol-2-yl]-Propionimidic Ethyl Ether

The preparation of N-[1-(N,N,N,N-tetramethylphosphoramidoyl)-1H-benzimidazol-2-yl]-proponimidic ethyl ester 2 has been achieved by the reaction of N-(1H-benzimidazol-2-yl)-proponimidic acid ethyl ester 1 with N,N,N,N-tetramethylchlorophosphoramide. The structure of compound 2 has been determined by X-ray diffraction. The results of (¹H, ¹³C, ³¹P) NMR, IR, EI-MS spectral data are consistent with those obtained from the X-ray diffraction. The compound crystallizes in the triclinic system, following the EsZ conformation. In the crystal, there are two weak C3–H3s1 and C15–H15sO1 intermolecular hydrogen bonds.     

Convergent synthesis of 2′,3′-dideoxy-3′-mercapto nucleosides — Potential anti-HIV agents

Summary Methyl 3-benzoylthio-5-O-tert-butyldiphenylsilyl-2,3-dideoxy--D-erythro-pentofuranoside (4) and its corresponding anomer5 were synthesized in four steps from 2-deoxy-D-ribose and used as substrates for the synthesis of nucleosides by condensation with silylated thymidine and N⁶-isobutyryladenine. The nucleosides were deprotected by treatment with Bu₄NF inTHF followed by reaction with MeONa in MeOH to give 3-deoxy-3-mercaptothymidine (8), 2,3-dideoxy-3-mercaptoadenosine (15) and its corresponding anomer16. In the latter reactions it was important to use degassed solvents to minimize formation of the corresponding disulfides of purine nucleosides. Using Bu₄NF, without subsequent reaction with MeONa in the deprotection reaction, resulted in intermolecular transesterification reactions.On leave from Chemistry Department, Faculties of Science and Education, Tanta University, Tanta, Egypt     

Conformational peculiarities of a new heterocyclic dihydrothienothiopyranoisoxazole system

The crystalline and molecular structures of 3H-3a,4-dihydro-7-methylthieno[3,2:5,6]thiopyrano[4,3-c]isoxazole and 3H-3a,4-dihydro-3-isopropoxycarbonyl-3a,7-dimethylthieno[3,2:5,6]thiopyrano[4,3-c]isoxazole are determined by X-ray analysis. The effect of steric factors on intramolecular 1,3-dipolar cycloaddition is shown.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 302–304, February, 1995.This work was financially supported by the Russian Foundation for Basic Research (Project No. 93-03-18461).     

Synthesis of formyl derivatives of benzocrown ethers containing N,S, and O heteroatoms in the macrocycle

A method for the synthesis of 4-bromobenzodithia-15(18)-crown-5(6) and 4-bromobenzodiaza-15 (18)-crown-5(6) by condensation of 3,4-di(2-haloethoxy)bromobenzene with polyoxaalkanes containing terminal SH or NHMe groups was suggested. The method for the synthesis of formyl derivatives of benzocrowns containing N, S, and O heteroatoms in the macrocycle based on the metallation of appropriate bromo derivatives with BuⁿLi followed by treatment of the resulting organolithium intermediates with DMF was developed. Oximes and semicarbazones of benzaldehydes containing a crown ether fragment were obtained, and their transformation into the original aldehydes by treatment with KNO₂ in an acid medium was studied.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 121–128, January, 1995.This study was financially supported by the Russian Foundation for Basic Research (Grant No. 94-03-08-531) and the International Science Foundation (Grant M8Q000).