Synthesis and Crystal Structure of Rctt-1-(2-benzoxazolyl)-2-(4-chlorophenyl)-4-phenyl-3-(4-pyridinyl)cyclobutane

1INTRODUCTIONThephotodimerizationof1,2-bisarylethenederivativesisaconvenientwayforsynthesizingtetraarylsubstitutedcyclobutane.Forthisreason,thephotochemistryofstilbeneandstyrylpyridinederivativeshasbeenextensivelystudied[1,2].UpontheirradiationwithUVlight(?=300～400nm),thesemonomersareconvertedtohead-to-tailphotodimersinpolarsolventwithperfectyields.Inrecentyears,ourgrouphasbeenstudyingthephotodimerizationreactionsofheteroarylethenescontainingbenzoxazolyl[3]andphenyloxazolyl[4]groups.Itw…     

Synthesis of 2-, 4- and 5-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans and their leukotriene B4 receptor antagonistic activity

Variable benzo[b]furan derivatives having (E)- and (Z)-2-alkylcarbamoyl-1-methylvinyl groups at the 2-, 4- and 5-positions and a carboxylpropoxy or (1-phenyl)ethoxy group at the 7-position were prepared to find novel and selective leukotriene B4(LTB4) receptor antagonists. (E)-2-(2-diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (4v) showed selective inhibition to the human BLT2 receptor (hBLT2). On the other hand, (E)-2-acetyl-4-(2-diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (7v) inhibited both human BLT(1) receptor (hBLT1) and hBLT2. The (E)-2-(2-diethylcarbamoyl-1-methylvinyl) group lay on approximately the same plane as the benzo[b]furan ring, whereas the (E)-4-(2-diethylcarbamoyl-1-methylvinyl) group had the torsion angle (45.7 degree) from the benzo[b]furan ring plane. However, the (Z)-(2-alkylcarbamoyl-1-methylvinyl)benzo[b]furans were inactive. The inhibitory activity depended on the conformation of the 2-diethylcarbamoyl-1-methylvinyl group.     

Le longifolène—XVIII : Solvolyse des tosylates de (7αH)-longifolanyle-3α et 3β

Solvolysis of the 3α- and 3β-tosylates of (7αH)-longifolanyl gives only products of ring contraction, but no longifolene. The mechanism of the solvolysis is discussed, on the basis of a ring inversion in the case of the 3β substituent. This ring inversion is proved by the NMR spectrum of 4α-²H(7αH)-longifolan-3β-ol. obtained by stereoselective monodeuteriation of (7αH)-longifolan-3-one and reduction.     

Reactions of the heavier group 14 element alkyne analogues Ar'EEAr' (Ar' = C6H3-2,6(C6H3-2,6-Pri2)2; E = Ge, Sn) with unsaturated molecules: probing the character of the EE multiple bonds

Reactions of the alkyne analogues Ar'EEAr' (Ar' = C6H3-2,6(C6H3-2,6-Pr(i)2)2; E = Ge (1); Sn (2)) with unsaturated molecules are described. Reaction of 1 and 2 with azobenzene afforded the new hydrazine derivatives Ar'E{(Ph)NN(Ph)}EAr' (E = Ge (3); Sn (4)). Treatment of 1 with Me3SiN3 gave the cyclic singlet diradicaloid Ar'Ge{mu2-(NSiMe3)}2GeAr' (5), whereas 2 afforded the monoimide bridged Ar'Sn{mu2-N(SiMe3)}SnAr' (6). Reaction of 1 with t-BuNC or PhCN yielded the adduct Ar'GeGe(CNBu(t))Ar' (7) or the ring compound (8). In contrast, the tin compound 2 did not react with either t-BuNC or PhCN. Treatment of 1 with N2CH(SiMe3) generated Ar'Ge{mu2-CH(SiMe3)}{mu2:eta2-N2CH(SiMe3)}{mu2-N2CH(SiMe3)}GeAr' (9) which contains ligands in three different bridging modes and no Ge-Ge bonding. Reaction of 1 with an excess of N(2)O gave a germanium peroxo species Ar'(HO)Ge(mu2-O)(mu2:eta2-O2)Ge(OH)Ar' (10) which features a ring. Oxidation of 1 by tetracyanoethylene (TCNE) led to cleavage of the Ge-Ge bond and formation of a large multiring system of formula Ar'Ge3+{(TCNE)2-}3{(GeAr')+}3. The digermyne 1 also reacted with 1 equiv of PhCPh to give the 1,2-digermacyclobutadiene 12, which has a ring, and with Me(3)SiCCH or PhCC-CCPh to activate a flanking C6H3-2,6-Pr(i)2 ring and give the tricyclic products 13 and 14. The "distannyne" 2 did not react with these acetylenes. Overall, the experiments showed that 1 is highly reactive toward unsaturated molecules, whereas the corresponding tin congener 2 is much less reactive. A possible explanation of the reactivity differences in terms of the extent of the singlet diradical character of the Ge-Ge and Sn-Sn bonds is discussed.     

Synthesis and Crystal Structure of 5-[（1H-1,2,4-Triazol-1- yl）methyl]-4-（2,3-dimethoxybenzylideneamino）-2- 2H-1,2,4-triazole-3（4H）-thione Monohydrate

1 INTRODUCTION Heterocyclic compounds bearing the 1,2,4-tri- azole moiety have attracted considerable attention over the past few decades since they exhibit some fungicidal activities against Puccinia recondite and applications in the field of root-growth regu- lation[1~3]. Meanwhile, 4-amino-5-mercapto-1,2, 4-triazole moiety has great versatility in fusing tovarious ring systems and possesses a broad spec- trum of biological activities[4, 5]. In our con- tinuous work directed towards the…     

Unravelling the reaction mechanism of the reductive ring contraction of 1,2-pyridazines

Substituted pyrroles may be synthesized from selected 1,2-pyridazines through a reductive ring contraction involving the addition of four electrons and four protons. Our density functional theory computations of this reaction mechanism show that the first reduction event must be preceded by the uptake of one proton by 1,2-pyridazine and that the reaction proceeds through a 2e(-)/3H(+)-bearing intermediate. In the absence of electron-withdrawing groups able to resonate charge away from the ring, this intermediate lies too high in energy, making the reaction sequence thermodynamically inaccessible. After another two-electron reduction and the addition of two more protons, the original 1,2-pyridazine ring opens. Ring contraction and ammonia elimination then proceed with very small barriers, irrespective of the substituents present in the original 1,2-pyridazine. By establishing the need for electron-withdrawing resonant groups in the 3- and 6-positions to stabilize the critical intermediate in the initial stages of the reaction, this work suggests that the scope of the reductive ring contraction of 1,2-pyridazines may be expanded to pyridazines bearing COCH(3) groups, amides or aryls in these positions. We also explain the lack of reactivity of unsubstituted 1,2-pyridazine and analyze the feasibility of bypassing the high energy 2e(-)/3H(+)-intermediate through disproportionation of earlier 2e(-)/2H(+)-bearing intermediates.     

Thromboxane A2 receptor antagonists. III. Synthesis and pharmacological activity of 6,6-dimethylbicyclo[3.1.1]heptane derivatives with a substituted sulfonylamino group at C-2

Four stereoisomers of the title compounds based on side chain ring junctions, (+)-7a, (+)-7b, (-)-7c and (-)-24, were synthesized from (-)-myrtenol and (+)-nopinone. The (1R,2R,3S,5S)-isomer (+)-7b had the most potent inhibitory activity against platelet aggregation and did not show partial agonist activity (shape change of platelets). We also synthesized the antipode, (-)-7b, and derivatives of (+)-7b with various kinds of substituents at the sulfonylamino group, 34a-n and p. The one-carbon homologated compound, (+)-58, was also prepared. The inhibitory activities of these compounds against platelet aggregation were measured.     

Recyclization of 2-(3,6-diaryl-2,5-dihydropyridazin-4-yl)-1H-benzimidazoles to 2-[(3,5-diarylpyrazol-4-yl)methyl]-1H-benzimidazoles

2-(3,6-Diaryl-2,5-dihydropyridazin-4-yl)-1H-benzimidazoles undergo a previously unknown type of recyclization of the pyridazine ring to a pyrazole to give 2-[(3,5-diarylpyrazol-4-yl)methyl]-1H-benzimidazoles. It is suggested that the mechanism of this conversion, which includes formation of a secondary enhydrazine group in the diazine ring and its subsequent contraction, occurs after the intramolecular formation and opening of a cyclopropane ring. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 853–861, June, 2008.     

Synthesis and investigation of the boron cluster anion [7-(2'-pyridyl)-7,8-nido-dicarbaundecaborate] and its protonated form

The structurally chiral [7-(2'-pyridyl)-7,8-nido-C(2)B(9)H(11)](-), [](-), anion was prepared by a partial degradation reaction of 1-(2'-pyridyl)-1,2-closo-C(2)B(10)H(11). From this anion a protonated specie, H[7-(2'-pyridyl)-7,8-nido-C(2)B(9)H(11)] , and a tetramethylammonium salt, [NMe(4)][7-(2'-pyridyl)-7,8-nido-C(2)B(9)H(11)], [NMe(4)][] can be obtained. The (1)H{(11)B} DNMR study on in the temperature range from 298 to 203 K identified the weakly basic nitrogen atom in the pyridine ring as the proton accepting site in solid state and low temperature and revealed pronounced weakening of the nitrogen-proton interaction while the temperature increases. Capillary electrophoresis and X-ray diffraction confirmed the pyridine nitrogen atom as the proton binding site. Separation of the electrophoretically pure racemic [7-(2'-pyridyl)-7,8-nido-C(2)B(9)H(11)](-) ion into two peaks by the chiral selector beta-cyclodextrine has been achieved.     

Photoisomerization of 2H,6H-thiin-3-one 1-oxides to 3H,7H-[1,2]oxathiepin-4-ones

Oxidation of 2H, 6H-thiin-3-ones 1a – c with 3-chloroperbenzoic acid affords the corresponding 1-oxides 2a – c . On irradiation (350 nm) in either benzene or MeCN, these cyclic sulfoxides 2 isomerize to 3H, 7H-1,2-oxathiepin-4-ones 3 . The tetramethyl derivative 3a is isolated by flash chromatography at ?10°, but, at higher temperatures, it undergoes ring contraction and H₂O elimination to give 4,4-dimethyl-2(2-methylprop-2enylidene)thietan-3-one ( 4 ). Diemthyloxathiepinones 3b and 3c undergo ring contraction in MeOH to afford 1-(4-methylthiophen-2-yl)ethanone ( 5 ) and two diastereoisomeric 4,4-dimethyl-2-methoxy-2-(1-methoxyethyl)thietan-3-ones ( 6 and 7 , respectively).     

Synthesis of new 14-membered macrolide antibiotics via a novel ring contraction metathesis

[reaction: see text] A novel ring opening ring closing metathesis (ROM-RCM) was demonstrated for cyclic conjugated dienes, effecting the excision of a C(2)H(2) unit and a net ring contraction. Applying the ring contraction metathesis, new 14-membered ring macrolide antibiotics were synthesized in a single step from existing 16-membered ring macrolides. This new class of macrolide antibiotics will provide access to new therapeutics for the treatment of macrolide-resistant bacterial infections.     

Electrophoretic investigation of the boron cluster anion [7-(2'-pyridyl)-nido-7,8-dicarbaundecaborate]- and its protonated zwitterionic product

ACN is a better solvent than methanol for both [NMe(4)] [7-(2'-pyridyl)-nido-7,8-C(2)B(9)H(11)] and its protonated anion. The investigated laboratory preparations of the salt and of its protonated anion are electrophoretically pure solids stable for 2 months at 4 degrees C. At a longer storage, the solid salt is more stable than the solid protonated anion. In the 40:60 v/v water-methanol solvent, decomposition products of the salt anion are detectable after one-week storage of the salt solution at 4 degrees C. The protonated anion does not decompose for almost 1 year in water-organic solutions at 4 degrees C. The exchange of the proton between the protonated anion and the solution is reversible and fast at room temperature. The pH dependence of the mobility of the [7-(2(-pyridyl)-nido-7,8-C(2)B(9)H(11)](-) anion reveals that the basicity of the nitrogen atom in the pyridine ring is not significantly affected by the bonding of the pyridyl group to the nido-7,8-C(2)B(9)H(11) cluster in position 7 and that the proton from the solution is accepted by the nitrogen atom in the 2-pyridyl ring. The UV-spectra of the salt and of its protonated anion indicate that the accepted proton is probably slightly shifted to the open face of the nido-7,8-C(2)B(9)H(11) cluster. The [1](-) is chiral.     

Synthesis, Crystal Structure and Fungicidal Activity of 3- ( 4- Chloro- 3- ethyl- 1 -methyl- 1 H- pyrazol- 5-yl ) - 6- (E) phenylvinyltriazolo [ 3, 4-b ] - 1,3, 4-thiadiazole

1　ＩＮＴＲＯＤＵＣＴＩＯＮＩｎｒｅｃｅｎｔｙｅａｒｓ ,ｔｒｉａｚｏｌｏ[3,4, ｂ] 1 ,3,4 ｔｈｉａｄｉａｚｏｌｅｄｅｒｉｖａｔｉｖｅｓｈａｖｅｂｅｅｎａｔ ｔｒａｃｔｉｎｇｍｕｃｈａｔｔｅｎｔｉｏｎｆｒｏｍｃｈｅｍｉｓｔｓａｎｄｐｈａｒｍａｃｏｌｏｇｉｓｔｓｂｅｃａｕｓｅｔｈｅｙｓｈｏｗｂｒｏａｄｓｐｅｃｔｒａｏｆｂｉｏｌｏｇｉｃａｌａｃｔｉｖｉｔｉｅｓ,ｓｕｃｈａｓｉｎｓｅｃｔｉｃｉｄａｌ[1 ] ,ａｎｔｉｆｕｎｇａｌ[2 ] ,ｈｅｒｂｉｃｉｄａｌ[3] ,ａｎ ｔｉｂａｃｔｅｒｉａｌ[4] ,ｈｙｐｏｔｅｎｓｉｖ…     

(E)-1-alkyl-4-

(E)-1-Alkyl-4-[2-(alkylsulfonyl)-1-ethenyl]pyridinium salts were synthesized in two steps. These sulfones were stable at pH 7.3 and underwent a nucleophilic vinylic substitution (S(N)V) with mercaptans, including thiouracile, to give the corresponding 4-(thiovinyl)-pyridinium salts. The X-ray diffraction structure of (E)-1-methyl-4-[2-(ethylsulfanyl)-1-ethenyl]pyridinium iodide indicated conjugation of the sulfur with the pyridinium ring. (Z)-1-Methyl-4-[2-(methylsulfanyl)-1-ethenyl]pyridinium iodide, prepared from the corresponding thioether by reaction with methyl iodide in diethyl ether, underwent isomerization to the E isomer in a first-order reaction in deuterated [D6]DMSO with an activation energy of 14 kcalmol(-1). At pH 7, the (E)-1-methyl-4-[2-(methylsulfonyl)-1-ethenyl]pyridinium iodide (19) reacted specifically with thiols. The reaction of this sulfone with glutathione in a TES buffer at pH 7 was a second-order reaction (k = 4,100 M(-1)s(-1) at 30 degrees C) and gave the corresponding substitution product with an intense long wavelength absorption band (lambdamax=360 nm, epsilon = 27,500 M(-1)cm(-1)). The modification of different enzymes of known structure with 19 showed the high selectivity of this reagent towards thiol groups and its usefulness in the quantitative determination of free thiol groups in proteins.     

Remarkable synthesis of 2-(Z)-6-(E)-4H-[1,4]-thiazepin-5-ones by zwitteronic rhodium-catalyzed chemo- and regioselective cyclohyrocarbonylative ring expansion of acetylenic thiazoles.

Cyclohydrocarbonylative ring expansion of acetylenic thiazoles in the presence of CO, H(2), and catalytic quantities of the zwitterionic rhodium complex (eta(6)-C(6)H(5)BPh(3))(-)Rh(+)(1,5-COD) and triphenyl phosphite affords thiazepinones in 61 to 90% yields. This novel transformation of a 5- to a 7-membered heterocycle is readily applied to acetylenic thiazoles containing hydro, alkyl, alkyl halide, vinyl, and benzo substitutents in positions 4 and 5 of the thiazole ring in addition to alkyl-, ether-, ester-, vinyl-, and aryl-substituted alkynes at position 2.     

Fluorinated pyrido[2,3-c]pyridazines. II. Synthesis and antibacterial activity of 1,7-disubstituted 6-fluoro-4(1H)-oxopyrido[2,3-c]pyridazine-3- carboxylic acids

Chemical modification of pyridonecarboxylic acid antibacterials with a 1,8-naphthyridine ring, such as enoxacin and tosufloxacin, to their 2-aza derivatives was studied. A new series of 1,7-disubstituted 6-fluoro-4(1H)-oxopyrido[2,3-c]pridazine-3-carboxylic acids (25-27) was prepared by a route involving either alkylation of ethyl 6-fluoro-4(1H)-oxo-7-(p-tolylthio)pyrido[2,3-c]pyridazine-3-carbox ylate (7) or intramolecular cyclization of ethyl 2-(2,6-dichloro-5-fluoronicotinoyl)-2-[2-(p-fluorophenyl)hydraz ono]acetate, (20), followed by displacement reaction with cyclic amines at C-7; the N-1 substituent in these compounds included of ethyl, 2-fluoroethyl and p-fluorophenyl groups, and the C-7 functional group comprised variously-substituted piperazines and pyrrolidines. Antibacterial activities of these compounds were markedly inferior to those of enoxacin and tosufloxacin.     

Infrared spectroscopy of gas phase benzenium ions: protonated benzene and protonated toluene, from 750 to 3400 cm-1

Gas phase C 6H 7 (+) and C 7H 9 (+) ions are studied with infrared photodissociation spectroscopy (IRPD) and the method of rare gas tagging. The ions are produced in a pulsed electric discharge supersonic expansion source from benzene or toluene precursors. We observe exclusively the formation of either the C 2 v benzenium ion (protonated benzene) or the para isomer of the toluenium ion (protonated toluene). The infrared spectral signatures associated with each ion are established between 750 and 3400 cm (-1). Comparing the gas phase spectrum of the benzenium ion to the spectrum obtained in a superacid matrix [ Perkampus, H. H.; Baumgarten, E. Angew. Chem. Int. Ed. 1964, 3, 776 ], we find that the C 2 v structure of the gas phase species is minimally affected by the matrix environment. An intense band near 1610 cm (-1) is observed for both ions and is indicative of the allylic pi-electron density associated with the six membered ring in these systems. This spectral signature, also observed for alkyl substituted benzenium ions and protonated naphthalene, compares favorably with the interstellar, unidentified infrared emission band near 6.2 microm (1613 cm (-1)).     

Quinazolines and 1,4-benzodiazepines. XLVI. Photochemistry of nitrones and oxaziridines

The cyclic nitrones 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5a ) and 1,3-dihydro-7-methylthio-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5b ) are photoisomerized to readily isolable oxaziridines, 7-chloro-4,5-epoxy-5-phenyl-1,3,4–5-tetrahydro-2H-1,4-benzodiazepin-2-one ( 6a ) and 4,5-epoxy-5-phenyl-1,3,4,5-tetrahydro-7-methylthio-2H-1,4-benzo-diazepin-2-one ( 6b ). Oxaziridine 6b upon further irradiation gave ring expansion and ring contraction products, 4,6-dihydro-2-phenyl-9-methylthio-5H-1,3,6-benzoxadiazocin-5-one ( 7b ) and 4-benzoyl-3,4-dihydro-6-methylthioquinoxalin-2(1H)-one ( 8b ) respectively. The ring contraction product, 4-benzoyl-6-chloro-3,4-dihydroquinoxalin-2(1H)-one ( 8a ), was obtained from irradiation of oxaziridine 6a .     

(+)-(1S,7aS)-1-羟基-7a-甲基-茚满-4-烯-5-酮的合成及其烷基化反应研究

以2-甲基-2-(3-丁酮)环戊烷-1,3-二酮为原料,经环合和还原反应合成了手性(+)-(1S,7aS)-1-羟基-7a-甲基-茚满-4-烯-5-酮(3);3在其羟基未进行保护情况下与不同芳香侧链进行α,β-不饱和酮的α-位烷基化反应,制备了5个3的衍生物,其结构经1H NMR确证。     

The stereodivergent asymmetric synthesis of a range of 2-(1′-hydroxyalkyl)phenols

The use of the (S)-α-methylbenzyl group as a chiral auxiliary has allowed the diastereoselective ortho-deprotonation of a chromium tricarbonyl complexed phenoxy ring. When the resultant ortho-anion is treated with an aldehyde two diastereoisomeric complexes are formed, in relatively poor dr, which differ in the configuration of the newly formed benzylic stereogenic centre. However, both ortho-formylation followed by treatment with Grignard reagents and ortho-acylation followed by reduction with Super-Hydride^® were found to be completely diastereoselective, giving access to either epimer of the corresponding benzylic alcohol complexes in >99:1 dr. Subsequent oxidative removal of the chromium tricarbonyl unit, followed by cleavage of the O-α-methylbenzyl chiral auxiliary gives enantiopure 2-(1′-hydroxyalkyl)phenols. Following this stereodivergent procedure, either enantiomer of the product may be accessed from a single antipode of [(α-methylbenzyloxy)benzene]Cr(CO)₃.