新型甾体N,N-二甲基缩氨硫腙类化合物的合成及其抗肿瘤活性

以乙醇（或甲醇为溶剂）,冰醋酸为催化剂,去氢表雄酮、孕烯醇酮、雌酮和3,5-二羟基-6-甲酰基-B-降胆甾烷分别与N,N-二甲基硫代氨基脲经缩合反应,合成了4个新型的具有不同甾核结构特征的甾体N,N-二甲基缩氨硫腙类化合物（1～4）,其结构经¹H NMR, ¹³C NMR, IR和HR-EI-MS表征。采用MTT法测定了1~4对肝癌细胞(HepG)、人鼻咽癌细胞(CNE-2)和人肾上皮细胞（HEK-293T）的体外抑制细胞生长增殖活性。结果表明：1~3对HepG和CNE-2具有明显的抑制活性。     

新型含胍基和季铵基团壳聚糖衍生物的合成

N,N-二甲基-1,3-丙二胺与单氰胺经亲核加成反应制得中间体N,N-二甲基-N′-胍基-1,3-丙二胺（2）; 以壳聚糖为起始原料,依次与氯乙酸、环氧氯丙烷经取代反应制得N-（1-羟基-3-氯丙基）-羧甲基壳聚糖（4）; 4与2经季铵化反应合成了一系列含有胍基和季胺基团的羧甲基壳聚糖衍生物（5）,其结构经¹H NMR, IR和元素分析表征。研究了反应配比［γ=m（2）∶m（4）］和反应时间对5取代度的影响,结果表明,当γ为3∶1,反应时间为10 h时,取代度最高(73%)。     

金刚烷基甜菜碱型和季铵盐阳离子型表面活性剂的合成研究

以金刚烷胺为起始反应物,首先在过量甲酸存在下,与甲醛发生埃斯韦勒-克拉克甲基化反应合成了N,N-二甲基金刚烷叔胺,在此基础上通过N,N-二甲基金刚烷叔胺与氯乙酸钠、溴代正丁烷、溴代正辛烷、溴代十二烷、溴代十六烷等一系列季铵化试剂的季铵化反应,分别合成了N,N-二甲基金刚烷甜菜碱型表面活性剂及N-(1-金刚烷基)-N,N-二甲基正丁基溴化铵、N-(1-金刚烷基)-N,N-二甲基辛基溴化铵、N-(1-金刚烷基)-N,N-二甲基十二烷基溴化铵、N-(1-金刚烷基)-N,N-二甲基十六烷基溴化铵等金刚烷季铵盐阳离子型表面活性剂,产率分别为75%,75%,61%,44%,54%.采用元素分析,IR,1H NMR等分析手段对5种产物进行了结构鉴定,测试了各种金刚烷表面活性剂水溶液的表面张力.     

一种新的选择性氧化苏-（1S，2S）-2-（N，N-二甲胺基）-1-（对硝基苯基）-1，3-丙二醇的N-甲基为N-甲酰基的方法

报告多官能团化合物苏—(1S，2S)—2—(N，N-二甲胺基)—1—(对硝基苯基)—1，3—丙二醇与聚合物支载条件下的溴试剂发生的—种新的选择性N-甲基氧化为N-甲酰基的反应．在Na2HPO4存在下，苏—(1S，2S)—2—(N，N-二甲胺基)—1—(对硝基苯基)—1，3．丙二醇于水—CCL4体系中被717阴离子交换树脂支载的溴在60℃氧化24h给出51％收率的苏—(1S，2S)—2—(N-甲基—N—甲酰胺基)—1—(对硝基苯基)-1，3-丙二醇.这种选择性N—甲基氧化为N-甲酰基的反应在2—氨基—1，3—丙二醇衍生物化学中是第—次观察到．     

Salen Mn（Ⅲ）配合物的合成及其在离子液体中对苯乙烯环氧化反应的催化性能

合成了在5,5’位上分别含羟基叔胺基和酯基叔胺基取代基的新型手性水杨醛Schiff碱的Salen Mn（Ⅲ）配合物1～4．在CH2Cl2／H2O反应体系中,以吡啶氮氧化物（PyNO）为助催化剂,NaCl0为氧化剂,考察了配合物1—4对苯乙烯环氧化的催化性能．以氯化-双[3-（叔丁基）-5-（N,N-二（乙醇基）氨基亚甲基）水杨醛]缩（1r,2R）-二苯基乙二胺[N,N’,O,O’]锰（Ⅲ）2和氯化-双[3-（叔丁基）-5-（N,N-二（乙酰乙酯基）氨基亚甲基）水杨醛]缩（1R,2R）-二苯基乙二胺[N,N’,O,O’]锰（11I）4为例,研究了不同的离子液体[BMIM]PF6和[BMIM]BF4对苯乙烯环氧化反应的影响．结果显示,两种离子液体的加入均能使催化剂循环使用,在离子液体[BMIM]PF。中,配合物2和4催化得到的环氧化物ee％值分别为53．2％和55．8％,且催化剂可以重复使用四次,效果好于在离子液体[BMIM]BF4中对苯乙烯的催化的影响．     

Cu(ClO4)2诱导的N-苯基二吡啶甲基胺的邻位苯甲基化及其溴桥联铜配合物的形成

N-苯基二吡啶甲基胺和苯甲基溴在Cu(ClO4)2存在的条件下反应导致N-苯基二吡啶甲基胺的邻位苯甲基化和一个新的溴桥联的双核铜配合物的形成。实验结果显示阴离子显著影响反应的选择性,CuCl2和Cu(NO3)2不能提高N-苯基二吡啶甲基胺邻位苯甲基化的选择性。NMR和元素分析数据证实N-苯基二吡啶甲基胺邻位苯甲基化产物的形成。X-射线晶体结构数据表明溴桥联的双核铜配合物中铜原子被3个N原子,1个配位溴离子和1个μ2-桥联的溴结合形成扭曲的三角双锥的构型。研究结果表明Cu(ClO4)2可作为N-苯基二吡啶甲基胺邻位烷基化反应的催化剂。研究结果有助于设计新的选择性苯甲基化催化剂。     

[5C+1N]成环反应：吡啶-4(1H)酮类化合物的一种简便合成方法

用N,N-二甲基丙烯酰基二硫缩烯酮类化合物2与各种脂肪胺类化合物3在N,N-二甲基甲酰胺溶剂中60 ℃条件下,氮乙烯基发生分子内的亲核取代反应,通过[5C+1N]成环反应,合成了系列吡啶-4(1H)酮类化合物4,产率在75%~95%之间。     

无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应

开发了无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应.应用该反应在甲醇中回流,以39%~83%的收率合成了一系列4-(N-(2,2-二氟乙基)(N-杂环芳基甲基)氨基)-5,5-二取代呋喃-2(5H)-酮,其结构经1H NMR,13C NMR和HR-ESI-MS表征,并进一步通过3-氯-4-(N-2,2-二氟乙基)(N-嘧啶-5-基甲基胺基)-5,5-螺(4-甲氧基环己基)呋喃-2(5H)-酮(8)的晶体衍射间接证实.测试了所合成化合物的生物活性,结果表明,在600μg·mL^-1浓度时4-(N-2,2-二氟乙基)(N-6-氯吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3a)和4-(N-2,2-二.氟乙基)(N-6-氟吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3c)对桃蚜的死亡率均为100%.     

2-苯亚胺官能化吲哚基铕胺基配合物与芳基取代甲脒的反应性（英文）

2-(苯亚胺基次甲基)吲哚铕胺基配合物[η1∶η1-2-(C6H5NH=CH)C8H5N]2Eu[N(Si Me3)2](1)与二芳基取代甲脒(2,6-R2C6H3N=CHNH(C6H3R2-2,6)(R=iPr(2),Me(3))经过配体交换反应,分别得到了含吲哚基脒基铕配合物[η1∶η1-2-(C6H5NH=CH)C8H5N]Eu[(η3-2,6-iPr2C6H3)N=CHN(C6H3iPr2-2,6)][N(Si Me3)2](4)和含脒基的稀土铕配合物[(η3-2,6-Me2C6H3)N=CHN(C6H3Me2-2,6)]2Eu[N(Si Me3)2](5)。结果表明,脒基的位阻显著影响了吲哚基稀土金属胺基配合物与二芳基取代甲脒的配体交换反应。配合物4和5通过IR、元素分析和X射线单晶衍射分析进行了表征。     

无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应（英文）

开发了无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应.应用该反应在甲醇中回流,以39%～83%的收率合成了一系列4-(N-(2,2-二氟乙基)(N-杂环芳基甲基)氨基)-5,5-二取代呋喃-2(5H)-酮,其结构经~1H NMR, ~(13)C NMR和HR-ESI-MS表征,并进一步通过3-氯-4-((N-2,2-二氟乙基)(N-嘧啶-5-基甲基胺基)-5,5-螺(4-甲氧基环己基)呋喃-2(5H)-酮(8)的晶体衍射间接证实.测试了所合成化合物的生物活性,结果表明,在600μg·mL~(-1)浓度时4-((N-2,2-二氟乙基)(N-6-氯吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3a)和4-((N-2,2-二氟乙基)(N-6-氟吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3c)对桃蚜的死亡率均为100%.     

2-(苯并吖啶酮)-乙基咪唑酸酯探针对荧光和质谱的双增敏作用

采用3种不同衍生方法对胺类化合物进行标记,比较衍生效率的差别,给出最优方法:5-(2-羟乙基)-(苯并吖啶酮与N,N-羰基双咪唑(CDI)缩合形成的双敏感探针2-(苯并吖啶酮)-乙基咪唑酸酯(BAEIC)与胺的衍生效率最高,产物稳定。BAEIC在N,N-二甲基甲酰胺(DMF)溶剂中以4-二甲氨基吡啶(DMAP)为催化剂,在80℃条件下与胺反应生成的亲核取代物,不仅表现出强烈的荧光,同时具有很强的质谱离子化能力。估算了衍生物在乙腈和甲醇水溶液中百分离子化值δ在5.62%～58.08%和2.14%～56.58%范围内。本方法具有良好的重现性,激发和发射波长为λex/λem=280/510nm,荧光检出限为0.12～0.59μg/L(8.6～79fmol);在线APCI-MS检出限为1.9～14μg/L(544～825fmol)。     

Reactivity of 2-thiohydantoins towards various electrophilic reagents: applications to the synthesis of new 2-ylidene-3,5-dihydro-4H-imidazol-4-ones

A new route to 5-(imidazolidin-2-ylidene)-2-methylsulfanyl-3,5-dihydro-imidazol-4-ones 4a-c using ketene dithioacetal intermediates 3a-c is described. The reactivity of thiohydantoin derivatives 2a-c towards N,N-dimethylformamide diethylacetal (DMF-DEA) was also explored using solvent-free technique under microwave irradiation (mu omega). The (1)H- and (13)C-NMR spectra of some representative products are discussed.     

An efficient synthesis of 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles

Ethyl α-(dimethylaminomethylene)-2-cyanomethyl-4-phenylquinoline-3-carboxylate(2) as new synthons directed to 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles was obtained by the condensation of ethyl 2-cyanomethyl-4-phenylquinoline-3-carboxylate(1) and N,N-dimethylformamide dimethyl acetal(DMFDMA).Reaction of this enamine with primary amines(3) in HOAc-DMF at120 ℃then affords 2-substituted 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitrile derivatives(4) in good yields by a tandem addition-elimination-cyclization reaction.     

Studies with polyfunctionally substituted heteroaromatics: New routes for the synthesis of polyfunctionally substituted pyridines and 1,2,4-triazolo[1,5-a]pyridines

The 1-substituted ethylidenemalononitriles 1a–c condensed with triethyl orthoformate in refluxing acetic anhydride to yield the dienes 2a–c . On the other hand, a mixture of N,N-dimethylformamide and triethyl orthoformate condensed with 1a–d to yield the N,N-dimethylaminopentadienonitriles 2d–g . The pentadienonitriles 2d–g were also formed from the reaction of 1a–d with dimethylformamide dimethylacetal in refluxing acetic acid. When compounds 1a–c were treated with dimethylformamide dimethylacetal in refluxing p-xylene, a mixture of 3 , 4 and 2e–g was formed. The reaction of 2a , b with hydrazine hydrate afforded the N-amino-2-iminopyridines 5a , b . These were converted into the triazolo[1,5-a]pyridines 8a–d on treatment with benzoyl chloride and with dimethylformamide dimethylacetal. On the other hand, the reaction of 2c with hydrazine hydrate afforded the pyrazolo[3,4-b]pyridine 7c . Treatment of 2a , c or 2e , g with cyanoethanoic hydrazide afforded the N-(cyanoacetamido)pyridines 9a , b . The dienes 2d , f , g afforded the pyridones 11a–c on treatment with acetic acid and hydrochloric acid mixture. Compounds 11b , c were also formed on treatment of 2b , c with acetic acid hydrochloric acid mixture. The reaction of 2d , g with ethanolic sodium ethoxide gave the ethoxypyridines 13a , b .     

Amide acetals in the synthesis of pyridothienopyrimidines

Methyl 3-amino-4-arylaminothieno[2,3-b]pyridine-2-carboxylates containing various substituents in the benzene ring were synthesized by the Thorpe-Ziegler reaction of 4-arylamino-2-chloropyridine-3-carbonitriles with methyl thioglycolates. The influence of the substituent in the benzene ring, acetal structure, the solvent and the process temperature on the reactions of obtained compounds with amide acetals was studied. It was established that reactions with dimethylacetamide dimethylacetal in toluene smoothly results in amidine derivatives, viz., methyl 4-arylamino-3-[1-(dimethylamino)ethylidene]aminothieno[2,3-b]pyridine-2-carboxylates, regardless of the substituent in the benzene ring. Analogous reaction of p-fluoroderivative with dimethylacetamide dimethylacetal in refluxing anhydrous ethanol leads to intramolecular cyclocondensation to produce substituted pyridothienopyrimidines, viz., 5H-1-thia-3,5,8-triazaacenaphthenes, in good yields. Amidine derivatives were the major products in the case of the coupling of aminothienopyridines with dimethylformamide dimethylacetal under the same conditions. A new approach to the synthesis of substituted pyridothienopyrimidines, viz., 3H-1-thia-3,5,8-triazaacenaphthylenes, based on the prolonged heating of methyl 4-arylamino-3-[1-(dimethylamino)ethylidene]aminothieno[2,3-b]pyridine-2-carboxylates in the excess of acetic anhydride was elaborated. Putative mechanisms of the processes concerned are given.     

Syntheses with nitriles. 60. Preparation of 4-amino-5-cyano-6-phenylpyrimidines from 2-amino-1,1-dicyano-2-phenylethene

The reaction of 2-amino-1,1-dicyanobut-1-ene and 2-amino-1,1-dicyano-2-phenylethene, respectively, with N,N-dimethylformamide dimethylacetal provided the corresponding (N,N-dimethylaminomethylene)amino derivatives. 2-[(N,N-Dimethylaminomethylene)amino]-1,1-dicyano-2-phenylethene was converted into 4-amino-5-cyano-6-phenylpyrimidines by treatment with primary aliphatic and aromatic amines. The structure of the reaction products was confirmed by ¹³C nmr spectroscopy.     

Proton-coupled electron transfer in ruthenium(II)-pterin complexes: formation of ruthenium-coordinated pterin radicals and their electronic structures

Ruthenium(II)-pterin complexes were prepared using tetradentate and tripodal tris(2-pyridylmethyl)amine (TPA) and tris(5-methyl-2-pyridylmethyl)amine (5-Me3-TPA) as auxiliary ligands together with 2-(N,N-dimethyl)-6,7-dimethylpterin (Hdmdmp) and 6,7-dimethylpterin (Hdmp) as pterin derivatives for ligands. Characterization was made by spectroscopic methods, X-ray crystallography, and electrochemical measurements. The pterin ligands coordinated to the ruthenium centers as monoanionic bidentate ligands via the 4-oxygen of the pyrimidinone moiety and the 5-nitrogen of the pyrazine parts. The striking feature is that the coordinated dmp- ligand exhibits a quinonoid structure rather than a deprotonated biopterin structure, showing a short C-N bond length for the 2-amino group. Those complexes exhibit reversible two-step protonation for both pterin derivatives coordinated to the ruthenium centers to give a drastic spectral change in the UV-vis spectroscopy. Doubly protonated Ru(II)-pterin complexes were stabilized by pi-back-bonding interaction and exhibited clear and reversible proton-coupled electron transfer (PCET) to give ruthenium-coordinated neutral monohydropterin radicals as intermediates of PCET processes. Those ESR spectra indicate that the unpaired electron delocalizes onto the PCET region (N5-C6-C7-N8) of the pyrazine moiety.     

一种新型Ni(Ⅱ)配位聚合物的合成、晶体结构和性质研究

溶剂热法合成了1个新配位聚合物{[Ni(C18H18N4O5)(DMF)]·(DMF}n.通过元素分析、红外光谱、热重以及X-射线单晶洐射对其进行了表征.该晶体为正交晶系,Pna21空间群.该化合物中,C18H18N4O5配体通过5个配位原子以及相邻的溶剂分子DMF上的1个配位原子与Ni(Ⅱ)原子配位,形成了1个扭曲的八面体配位构型.热重分析表明该化合物在140℃开始发生分解.     

Pyrazolines — Derivatives of 2-nitrochalcone

By the reaction of 2-nitrochalcone with hydrazine hydrate, 5-(2-nitrophenyl)-3-phenyl-1H-2-pyrazoline (I) and the hydrazone of 3-(5-(2-nitrophenyl)-3-phenyl-2-pyrazolin-1-yl)-3-(2-nitrophenyl)propiophenol (II) have been prepared. The acylation of both compounds I and II leads to N-acyl derivatives of the first. The acylating ability of formamide and N,N-dimethylformamide was observed in reactions with pyrazoline I. An x-ray structural study was carried out on compound II.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 360–366, March, 1993.     

Reactions with dimethylformamide‐dimethylacetal: Synthesis and reactions of several new pyridine and pyrazolo[3,4‐b]pyridine derivatives

6‐Aminopyridine‐2(1H)‐thiones 1a,b reacted with dimethylformamide‐dimethylacetal (DMF‐DMA) to give the corresponding 6‐{[(N,N‐dimethylamino)methylene]amino}pyridine derivatives 2a,b . The latter compounds reacted with hydrazine hydrate to afford the 3,6‐diamino‐1H‐pyrazolo[3,4‐b]pyridine derivative 4 and 3‐amino‐5‐hydrazino‐1H‐pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyrimidine derivative 7 , respectively. Compound 4 condensed with DMF‐DMA to yield the 3,6‐bis{[(N,N‐dimethylamino)methylene]amino}‐1H‐pyrazolo[3,4‐b]pyridine derivative 10 , which reacted with malononitrile to give the corresponding pyridopyrazolopyrimidine derivative 15 . © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:399–404, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20312