新型丁二炔-二酰胺大环化合物的合成及与TTF和DNP在溶液中的络合行为

由三甘醇和四甘醇出发,经炔丙基烷基化、Mitsunobu反应和Eglinton偶联反应3步合成了2个含均苯四甲酸二酰亚胺结构单元以及丁二炔结构单元的大环化合物,关环产率分别为81%和85%.大环化合物及中间体的化学结构经核磁共振氢谱、碳谱、低分辨质谱、高分辨质谱或元素分析等确认.通过氘代丙酮中1HNMR实验以及氯仿中紫外滴定实验研究了这类大环化合物与客体分子四硫富瓦烯(TTF)和1,5-二甲氧基萘(DNP)在溶液中的相互作用,结果发现,大环化合物的核磁化学位移及紫外光谱均发生变化.通过得到的主-客体间的络合常数可知,此类新型大环化合物与TTF和DNP之间有一定的络合作用.     

1,x-elimination reactions: extending the limits of a classical organic reaction

Alpha,omega-dibromo derivatives in which the two terminal carbon atom are separated by an unsaturated spacer unit ("pi spacer") undergo 1,x-elimination reactions (with x=6, 8, 10, and 14), using Mori's reagent (nBu3SnSiMe3/CsF). The resulting cumulenic intermediates cyclodimerize in a subsequent step yielding novel macrocyclic acetylenic and bridged aromatic compounds (cyclophanes). Thus 1,6-eliminations were carried out with dibromide 17 to yield 1,3,7,9-cyclododecatetrayne (20) and with benzylbromide 24 to provide cyclophanes 26 and 27. By 1,8-eliminations the 16-membered macrocycle 33 could be prepared from enediyne 31, the benzannelated 1,5-cyclooctadiyne 41 from dibromide 38, and a mixture of cyclophanes 45 and 46 from the precursor 43. 1,10-Eliminations were carried out successfully with dibromides 47, 50, and 53 yielding the corresponding unsaturated cyclophanes ("cyclophynes") 49, 52, and 55. The influence of the solvent on the cyclodimerization 47-->49 was investigated, with acetonitrile providing the highest yields. The heterophanes 59 a and b were obtained by 1,10-elimination of the precursor dibromides 57 a and b, and in an elimination experiment involving a 1:1 mixture of the dibromides 50 and 57 b the "mixed dimer" 60 was isolated, besides the homodimers 52 and 59 b. The method reached its limits with the 1,14-elimination of 68, 70, and 74 providing the cyclophanes 69, 71, and 75 in varying amounts. Two final debrominations with 76 and 77, which in principle could undergo 1,16- and 1,20-eliminations reactions, respectively, failed. The structures of the new cyclophanes 49, 50, 59 a, and 59 b were established by X-ray structural analysis; all other structure assignments rest on the usual spectroscopic and analytical data.     

Furopyridines. XIII. Reaction of 2-methylfuro[2,3-b]-, -[3,2-b]-, -[2,3-c]- and -[3,2-c]pyridines with lithium diisopropylamide

Lithiation of 2-methylfuro[2,3-b]- 1a , -[2,3-c]- 1c and -[3,2-c]pyridine 1d with lithium diisopropylamide at ?75° and subsequent treatment with deuterium chloride in deuterium oxide afforded 2-monodeuteriomethyl compounds 2a, 2c and 2d , while 2-methylfuro[3,2-b]pyridine 1b gave a mixture of 1b, 2b , 2-methyl-3-deuteriofuro[3,2-b]pyridine 2′b and 2-(1-proynyl)pyridin-3-ol 5 . The same reaction of 1a at ?40° gave 3-(1,2-propadienyl)pyridin-2-ol 3 and 3-(2-propynyl)pyridin-2-ol 4 . Reaction of the lithio intermediates from 1a, 1c and 1d with benzaldehyde, propionaldehyde and acetone afforded the corresponding alcohol derivatives 6a, 6c, 6d, 7a, 7c, 7d, 8a, 8c and 8d in excellent yield; while the reaction of lithio intermediate from 1b gave the expected alcohols 6b and 8b in lower yields accompanied by formation of 3-alkylated compounds 9, 11, 12 and compound 5 . While reaction of the intermediates from 1a, 1b and 1d with N,N-dimethylacetamide yielded the 2-acetonyl compounds 13a, 13b and 13d in good yield, the same reaction of 1c did not give any acetylated product but recovery of the starting compound almost quantitatively.     

具有酯基和酰氨基的新型杯[4]冠醚与杯[6]冠醚的合成

乙醇胺与氯乙酰氯反应得到Ⅳ一(2．氯乙酸酯基乙基)一氯乙酰胺(1)．1与杯 [4]芳烃和杯[6]芳烃分别在K2c03／苯和K2c03／甲苯体系中反应48 h，以37％和 25％的产率得到具有酯基和酰氨基的杯芳烃冠醚．经核磁、质谱、元素分析等表征 证实杯[4]冠醚为l，3．桥联方式，杯[6]冠醚为l，4．桥联方式，且均采取杯式构 象．     

新型六氢吡啶-2,3-并吲哚化合物的合成及其抗肿瘤活性

以3-取代氧化吲哚与丙烯酸酯为原料,经Michael加成反应制得中间体--3-丙酸酯取代氧化吲哚（3a~3d）; 3a~3d与甲胺发生酰胺化反应制得3 丙酰胺取代氧化吲哚（4a~4d）; 4a~4d用氢化铝锂还原-环化,合成了4个六氢吡啶-2,3-并吲哚化合物(5a~5d）; 5a和5b用氢化铝锂还原合成了2个六氢吡啶-2,3-并吲哚化合物（6a和6b）, 5a～5d, 6a和6b均为新化合物,总产率42%～61%,其结构经¹H NMR, ¹³C NMR和HR-ESI-MS表征。采用MTT法研究了5a～5d, 6a和6b对人肺癌细胞（A549）,人前列腺（PC-3）和人白血病细胞（K562）的体外抗肿瘤活性。结果表明：5b对A549, PC 3和K562的抑制活性均较好,其IC₅₀分别为27.2μmol·L^-1, 37.5 μmol·L^-1和21.7 μmol·L^-1。     

有生物活性的哒嗪酮-氨基甲酸酯类衍生物的合成

氨基甲酸酯衍生物;有生物活性的哒嗪酮-氨基甲酸酯类衍生物的合成     

An efficient route for synthesis of 5,6‐diphenylimidazo‐[2,1‐b]thiazoles as antibacterial agents

The reaction of 4,5‐diphenylimidazol‐2‐thione ( 1 ) with aromatic ketones 2a‐i using the acidified acetic acid method afforded the 4,5‐diphenyl(2‐imidazolylthio)acetophenones 3a‐h in good yields. While, the cyclized product 4i was obtained directly upon reaction of 1 with α‐acetyl naphthalene. Compounds 3a‐h were cyclized directly to the corresponding 3‐aryl‐5,6‐diphenylimidazo[2,1‐b]thiazoles (4a‐c) and ( 4e‐h ). In the same manner the reaction of 1 with aliphatic and/or alicyclic ketones gave the 3‐(4,5‐diphenyl‐2‐imidazolylthio)acetone derivatives 5a‐d , 2‐(4,5‐diphenylimidazolylthio)cycloalkanones 8a,d and the tricyclic compounds 9b‐c respectively. The cyclized compounds 6a‐d and 9a,d were obtained by cyclization of 5a‐d and 8a,b respectively. Oxidation of 1 gives the corresponding bis(4,5‐diphenyl‐2‐imidazolyl)‐disulfide ( 10 ) in 90% yield. Some of the synthesized compounds were tested for antifungal and antibacterial activity.     

Nickel(II) complexes of 3-acetyl-4,5-dihydro-1,2,4-triazole hydrazones

3-Acetyl-1,2,4-triazole hydrazones (3b,c) and methylhydrazone (4d) were prepared by reacting triazoles (1b–d) with an excess of hydrazines at room temperature. Square planar nickel(II) complexes (8b,c) of (3b,c) were obtained from their reaction with Ni(OAc)₂ in a 2:1 mol ratio in EtOH at room temperature. The spectral data suggest structures (8b,c) for the obtained complexes, which result from ring opening of the triazole ring followed by recyclization to give the 5-arylhydrazono-2,3-dihydro-4H-1,2,4-triazine ligand (7b,c). The reaction of triazole methylhydrazone (4d) with Ni(OAc)₂ in EtOH resulted, however, in the formation of the starting triazole (1d). All new compounds were characterized by elemental analysis, i.r., ¹H-n.m.r. ¹³C-n.m.r. and hrms.     

Some aspects of the chemistry of pyrimido[1,2-B]pyridazinones

On reacting the 3-aminopyridazines 1a,d,e with dimethyl acetylenedicarboxylate (DMAD), the pyrimido[1,2-b]pyridazin-2-(2H)-ones 2e-g , whereas starting from 1f , the 4(4H)-ones 5a and 3b,d were prepared. In the 2(2H)-one series, the reactions of 2b with various amino compounds resulted in various types of products. The reaction of N-methylaminopyridazines 1g,h with DMAD led to the endo-N-substituted derivatives 8a,b , whereas 1h with diethyl ethoxymethylenemalonate (DEM) gave the exo-N-substituted compound 1k. The constitution of the compounds was proved by spectroscopic and chemical evidences.     

Studies on the reaction of N‐(3‐carbethoxy‐4,5,6,7‐tetrahydrobenzo[b]thien‐2‐yl)‐N′‐phenylthiourea with hydrazine hydrate (Part 1)

The reaction of N‐(3‐carbethoxy‐4,5,6,7‐tetrahydrobenzo[b]thien‐2‐yl)‐N′‐phenylthiourea ( 1 ) with hydrazine hydrate in 1‐butanol afforded a mixture of compounds 2, 3 and 4 . Treatment of 3 and 4 with nitrous acid gave 6 and 8 respectively, while reactions of 3 with acetylacetone gave 7 . Synthesis of tetracyclic compounds 9a‐f and 11 from the reactions of 3 with ethyl orthoformate or appropriate acids, acid chloride, carbon disulphide and/or ethyl chloroformate. Also its reaction with isothiocyanate derivatives gave the corresponding thiosemicarbzides 12a,b which on, refluxing in alcoholic KOH gave the unexpected tetracyclic products 14a,b . Similarly the tetracyclic compounds 16a‐e and 19 were obtained by cyclization of 4 and 18 respectively.     

Synthese et etude des complexes [C5H4(CH2)3C5H4]Ti(C5H5)2 presentant un pont entre deux ligands cyclopentadienyles

The complex (di-η⁵-C₅H₄CH₂CH₂CH₂C₅H₄)Ti(η¹-C₅H₅)₂ (I) can be obtained unambiguously starting from the corresponding bridged titanocene dichloride. Attempts to synthesize the isomeric compounds (η⁵-C₅H₅)₂ Ti(di-η¹-C₅H₄-CH₂CH₂CH₂C₅H₄) (I′) by the action of a convenient bridged dianion on (C₅H₅)₂ TiCl₂ afford several compounds, one of them is the complex I. The possibility of interconversion of these complexes by a fluctional process is discussed.     

三氟亚乙基取代的N-苯甲酰基氮杂环丙烷的合成

发展了一种制备三氟亚乙基取代的N-苯甲酰基氮杂环丙烷的新颖方法. 三氟甲基取代的炔丙胺化合物1在盐酸作用下脱去叔丁基亚磺酰基得到三氟甲基炔丙胺盐酸盐2, 当用NaOH作碱对2进行苯甲酰化反应时意外地以中等产率获得了N-苯甲酰基-2-三氟亚乙基氮杂环丙烷类化合物3a～3c. 在类似条件下也可以从1出发采用“一锅法”制得氮杂环丙烷3d和3e. 化合物3b可以在酸催化下发生开环反应得到化合物6b. 化合物3和6的结构经IR, 1H NMR, 19F NMR, MS, HRMS和元素分析进行确证.     

Synthesis,Characterization, and Screening for Anti‐inflammatory and Antimicrobial Activity of Novel Indolyl Chalcone Derivatives

Because of the great biological importance of substituted indole derivatives, in the present study, a series of pyrazolylindole, thiazolylindole, and pyrimidinylindole derivatives have been synthesized with good yield. The precursor indolyl chalcone 2a – d was prepared by reaction of 3‐chloro‐1H‐indole‐2‐carbaldehyde 1 with different ketones. Then, compounds 3b – d , 4 , and 5a – d have been synthesized by the reaction of chalcones 2a – d with hydrazine, phenylhydrazine, and thiosemicarbazide. When the chalcone derivative 2b subjected to react with hydroxylamine hydrochloride gave isoxazolylindole derivative 6b . N‐thiazolidine pyrazolyl indole 7 was obtained by reacting compound 5a with ethyl chloroacetate. On the other hand, when chalcone derivative 2b allowed to react with urea and thiourea gave the corresponding pyrimidinylindole derivatives 8 and 9 . Finally, when chalcone derivative 2b reacted with ethyl cyanoacetate or malononitrile gave pyridinylindole derivatives 10 and 11 . The structures of the all synthesized compounds were elucidated on the basis of spectral analysis infrared, NMR, and mass spectroscopy. Some of the synthesized compounds were screened for their antimicrobial and anti‐inflammatory activity. Compound 4b was the highest antibacterial activity against all strains of bacteria with values higher than those of the corresponding reference antibiotics (ciprofloxacin and levofoxacin, respectively) and almost the same as (gemifloxacin, moxifloxacin, clindamycin, gentamycin, and streptomycin). Compounds 4 , 5 , 6 , and 7 showed high anti‐inflammatory activity compared with the standard drug indomethacin.     

6,7-二氧亚甲基-3-氮杂(硫杂)-1(2H,4H)吖啶酮及其衍生物的合成

氮杂吖啶酮;硫杂吖啶酮;杂环化合物;6;7-二氧亚甲基-3-氮杂(硫杂)-1(2H;4H)吖啶酮及其衍生物的合成     

Synthesis of 1‐methyl‐, 4‐nitro‐, 4‐amino‐and 4‐iodo‐1,2‐dihydro‐3H‐pyrazol‐3‐ones

4‐Aminopyrazole‐3‐ones 4b, e, f were prepared from pyrazole‐3‐ones 1b‐d in a four‐step reaction sequence. Reaction of the latter with methyl p‐toluenesulfonate gave 1‐methylpyrazol‐3‐ones 2b‐d . Compounds 2b‐d were treated with aqueous nitric acid to give 4‐nitropyrazol‐3‐ones 3b‐d. Reduction of compounds 3b‐d by catalytic hydrogenation with Pd‐C afforded the 4‐amino compounds 4b, e, f. Using similar reaction conditions, nitropyrazole‐3‐ones derivatives 2c, d were reduced into aminopyrazole‐3‐ones 5e, f. 4‐Iodopyrazole‐3‐ones 7a, 7c and 8 were prepared from the corresponding pyrazol‐3‐ones 2a, 2c and 6 and iodine monochloride or sodium azide and iodine monochloride.     

新型胍基葡萄糖苷的合成及生物活性

将2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖基异硫氰酸酯(1)与2-氨基-4/6-取代-苯并噻唑(2a~2e)反应, 生成糖基硫脲衍生物(3a~3e), 再在伯胺存在下经氯化汞脱硫, 得到一系列新的多乙酰基胍基糖苷类化合物(4a~4d, 5a~5d, 6a~6d, 7a~7d), 糖基的保护基团在甲醇钠/甲醇条件下脱除. 所有新化合物的结构均经IR, 1H NMR, MS谱和元素分析证实, 所得产物均为β-构型. 生物活性测试结果表明, 化合物4c, 6c, 8b, 8c等对HIV-1蛋白酶表现出了较高的抑制活性; 化合物7c具有抗流感乙型病毒活性; 化合物5e, 7c, 7d等对血管紧张素转化酶具有抑制活性.     

An unusual exchange between alkylidyne alkyl and bis(alkylidene) tungsten complexes promoted by phosphine coordination: kinetic, thermodynamic, and theoretical studies

d0 Tungsten alkylidyne alkyl complex (Me3SiCH2)3W(CSiMe3)(PMe3) (4a) was found to undergo a rare, PMe3-promoted exchange with its bis(alkylidene) tautomer (Me3SiCH2)2W(=CHSiMe3)2(PMe3) (4b). Thermodynamic studies of the exchange showed that 4b is favored and gave Keq and the enthalpy and entropy of the equilibrium: DeltaH degrees = -1.8(0.5) kcal/mol and DeltaS degrees = -1.5(1.7) eu. Kinetic studies of the alpha-H migration between 4a and 4b by variable-temperature NMR gave rate constants k1 and k-1 for the reversible reactions and activation enthalpies and entropies: DeltaH1 = 16.2(1.2) kcal/mol and DeltaS1 = -22.3(4.0) eu for the forward reaction (4a --> 4b); DeltaH2 = 18.0(1.3) kcal/mol and DeltaS2 = -20.9(4.3) eu for the reverse reaction (4b --> 4a). Ab initio calculations at the B3LYP level revealed that PMe3 binds with the bis(alkylidene) tautomer relatively more strongly than with the alkylidyne tautomer and thus stabilizes the bis(alkylidene) tautomer.     

One-Pot formation of novel [3+3] NH-CH2 bridged cyclophanes

The new [3+3] NH-CH₂ bridged cyclophanes bearing different functional groups and different cavity sizes were prepared in one pot by treating diamine derivatives with dialdehyde derivatives. Factors important for efficiently form-ing these macrocycles include reaction concentration (10 or 100?mmol), temperature (room temperature or 40–50?°C) and solvent (CHCl₃). Preliminary fluorescence spectrometer and HRMS-ESI studies demonstrated the inner cavity of the new [3+3] NH-CH₂ bridged cyclophanes bearing three hydroxyl groups (3c) as a new highly selective probe for the naked eye detection of Ag⁺ in PBS buffer.     

Synthesis,characterization and studies of new 3‐benzyl‐4H‐1,2,4‐triazole‐5‐thiol and thiazolo[3,2‐b][1,2,4]triazole‐5(6H)‐one heterocycles

3‐Benzyl‐4‐phenyl‐1,2,4‐triazole‐5‐thiol ( 1 ) was synthesized and used as starting material for preparation of 1,2,4‐triazole bearing substituted thiosemicarbazides moiety ( 4a‐d ) in high yields. The thiosemicarbazides 4a‐d were cyclized in basic medium to give two triazole rings linked by thiomethylene group ( 5a‐d ), while cyclization of thiosemicarbazides 4a‐d with chloroacetyl chloride in the presence of CHCl₃ and K₂CO₃ afforded the thiazolidinone derivatives 6a‐d . The reaction of thiosemicarbazides 4a‐c with phenacyl bromide in the presence of EtOH and fused CH₃COONa gave the corresponding thiazoline ring systems 7a‐c . Condensation of the 3‐benzyl‐1,2,4‐triazole‐5(1H)‐thiol ( 1 ) with chloroacetic acid and aromatic aldehydes ( 8a‐ g) in boiling acetic acid/acetic anhydride mixture in the presence of fused sodium acetate gave one single isomer only, which might be 9a‐g or 10a‐g . Upon application of Micheal addition reaction on compounds 9a‐e with cyclic secondary amines such as piperidine or morpholine the 2‐benzyl‐6‐(α‐amino‐aryl/methyl)‐1,3‐thiazolo[3,2‐ b][1,2,4]‐triazol‐5‐ols ( 11a‐j ) were obtained in good yields The structure of all new compounds were determined using both spectral and elemental analyses.     

Bridged cyclophosphazenes resulting from deprotonation reactions of cyclotriphophazenes bearing a P-NH group

Cyclotriphosphazene derivatives containing a P-NHR group in the side-chain react in the presence of a strong base to form stable intermolecular bridged products. Reaction of sodium hydride with mono-spiro cyclophosphazene derivatives having a P-NH group, N(3)P(3)Cl(4)[O(CH(2))(3)NH], (1a) or N(3)P(3)Cl(4)[CH(3)N(CH(2))(3)NH], (1b) leads to formation of bis-cyclophosphazenes bridged with an eight-membered cyclophosphazene ring in an ansa arrangement (2a, 2b) whereas reaction of sodium hydride with mono-amino cyclophosphazene derivatives [N(3)P(3)Cl(5)(NHR), R = n-hexyl, 3a; i-Pr, 3b; Ph, 3c] give bis-cyclophosphazenes bridged with a four-membered cyclophosphazane ring in a spiro arrangement (4a-c). In the latter reaction P-O-P bridged compounds (5a-c) were also obtained as a result of hydrolysis reactions associated with the amount of moisture in the solvent tetrahydrofuran. In addition, it was found that reaction of a mixture of cyclotriphosphazene with either mono spiro compound, (1a) or (1b), in the presence of sodium hydride lead to formation of the first examples of asymmetrically-bridged cyclophosphazenes (6a-b).