5-溴-7-氮杂吲哚的合成工艺研究

以7-氮杂吲哚为原料,经氢化还原、溴化和脱氢等三步反应,制备了5-溴-7-氮杂吲哚;研究了氢化还原和溴化反应的工艺条件。较佳工艺条件:1氢化还原,反应压力为4 MPa,反应温度为95℃,反应时间12 h,溴化,7-氮杂吲哚啉和溴素的摩尔比为1∶1.15,总收率74.7%。     

吡咯并[2,3-c]氮杂卓-4,8-二酮衍生物的合成

将N-(2-吡咯甲酰基)-β-丙氨酸甲酯(Ⅲ)与卤代烃经烷基化反应得到的产物水解,得到N-(1-烷基-2-吡咯甲酰基)-β-丙氨酸(Ⅱa～Ⅱc),收率84.7%～91.2%;以化合物Ⅱ为原料,在多聚磷酸-P2O5作用下,经分子内环化反应合成了标题化合物1-烷基-6,7-二氢-1H,5H-吡咯并[2,3-c]氮杂-4,8-二酮(Ⅰa～Ⅰc),收率69.1%～77.2%。3步反应总收率为61.8%～69.1%。测定了3个标题化合物对α-葡萄糖苷酶的抑制作用。     

6-(1-苯基-乙基)-8H-吡咯并[3,4-b]吡啶的合成

以2,3-吡啶二羧酸作为起始原料,通过环合、氢化及内酰胺还原反应合成标题化合物,作为合成莫西沙星侧链(S,S)-2,8-二氮杂双环[4.3.0]壬烷的新型中间体。对各个中间体制备过程中原料的用量比进行了探究:在2,3-吡啶二酸酐的制备中,2,3-吡啶二羧酸与SOCl2的物质的量比为1∶1.35;在6-(1-苯基-乙基)-吡咯并[3,4-b]吡啶-5,7-二酮的制备中,2,3-吡啶二酸酐与SOCl2的物质的量比为n(2,3-吡啶二酸酐)∶n(SOCl2)=1∶1.10;在目标产物的制备中,n(6-(1-苯基-乙基)-6H-吡咯并[3,4-b]吡啶-5,7-二酮)∶n(Na BH4)∶n(BF3·Et2O)=1∶3.2∶3.2×0.95。另外,在氢化还原反应中,选用冰醋酸作为反应溶剂,目标化合物总收率73.7%,并通过1HNMR对中间体及产物结构进行了确证。该研究为(S,S)-2,8-二氮杂双环[4.3.0]壬烷的合成提供了新思路。     

铑催化烯丙醇参与的N-苯基-7-氮杂吲哚的C-H烷基化研究

实现了铑催化的N-芳基-7-氮杂吲哚与烯丙醇的C-H烷基化反应,以中等至良好的收率得到了一系列含氮杂吲哚的β-芳基丁酮化合物。最佳反应条件为N-芳基-7-氮杂吲哚(0. 1 mmol),3-丁烯-2-醇(0. 3 mmol),[Cp*RhCl_2]_2(5mol%),AgSbF_6(20mol%),AgOAc (0. 2 mmol)和甲醇/水(v/v=200∶1,1 m L),在100℃下反应24 h。此反应具体良好的官能团兼容性,为含氮杂吲哚的β-芳基丁酮化合物提供了一种新颖、方便的合成方法。     

4-氯-7-氮杂吲哚的合成研究

4-氯-7-氮杂吲哚的合成通过过氧化、解离、氯化步骤实现:①氧化,7-氮杂吲哚和间氯过氧苯甲酸进行络和,形成过氧化络和物。②解离,通过碳酸钾溶液解离苯甲酸得到7-氮杂吲哚的过氧化物。③氯化,过氧化物进行氯化得到产品。对产品质量非常重要。     

浅谈7-氮杂吲哚是生物碱的重要骨架及其药理作用

7-氮杂吲哚衍生物是一类重要的化合物，其在生理学、药物学以及功能材料领域有着广泛的应用．本文着重阐述7-氮杂吲哚是生物碱的重要骨架及其药理作用。     

4-甲氧基-9H-吡啶并[2,3-b]吲哚的合成研究

以2-氯吡啶为原料,经N-氧化、硝化、甲氧基化、胺解、加成-消除、环合6步反应合成4-甲氧基-9H-吡啶并[2,3-b]吲哚。其结构经IR,1H NMR,MS进行了确证。并对反应条件进行了研究,确定优化反应条件为:n(4-甲氧基吡啶-N-氧化物)∶n(1-对甲苯磺酰基-1,2,3-苯并三氮唑)=1.5∶1,成环反应时间2 h。该合成总收率为35.0%。     

7-氮杂吲哚及其衍生物5-溴-7-氮杂吲哚的合成

7-氮杂吲哚是一种重要的杂环化合物,是合成维罗非尼、ABT-199等抗肿瘤药物的重要中间体,具有较高的生物医药价值。优化了合成7-氮杂吲哚的方法,以廉价易得的2-氨基-3-甲基吡啶为起始原料,经过两步反应,以48%的总收率得到7-氮杂吲哚。并在此合成方法的基础上进一步合成了5-溴-7-氮杂吲哚,经过三步反应,总收率达到43%。该合成方法具有原料易得、操作简便、路线简短、收率较高等优点。产物的结构经过核磁共振和高分辨质谱得到确认。     

6-氮杂-螺[3,4]辛烷盐酸盐的合成

以环丁酮(1)为起始原料,与磷酰乙酸三乙酯经Witting-Horner-Emmons反应得2-环丁烯基乙酸甲酯(2),然后与硝基甲烷经迈克尔加成得2-(1-硝基甲基)环丁基乙酸甲酯(3),再经氢化还原、分子内胺解得6-氮杂-螺[3,4]辛烷-7-酮(4),最后经氢化铝锂还原、酸化等5步反应得到目标化合物6-氮杂-螺[3,4]辛烷盐酸盐,总收率为27%。其结构经1H NMR和MS进行确证。     

7-溴-9-甲基-2,3,4,9-四氢-1H-吡啶并[3,4-b]吲哚的合成

以6-溴吲哚-3-甲醛为原料,通过N-甲基化、Henry反应、烯烃还原、硝基还原、Pictet-Spengler等反应5步合成得到7-溴-9-甲基-2,3,4,9-四氢-1H-吡啶并[3,4-b]吲哚的合成,5步反应总收率25.1%。产物结构经1H NMR和ESI-MS确证。并对色胺衍生物(5)与乙醛酸的Pictet-Spengler反应的条件进行考察,确定最佳反应条件为:浓盐酸为质子酸催化剂;反应温度50℃;反应时间8h。     

苯并[1,2,3]噻二唑-7-醛的合成

以2-氯-3,5-二硝基苯甲酸为起始原料,经过取代、酯化、还原重氮化等反应,合成了苯并[1,2,3]噻二唑-7-羧酸乙酯。并采用二异丁基氢化铝将其一步还原制备了苯并[1,2,3]噻二唑-7-醛。     

CONDENSATION PRODUCTS OF 7H-BENZO[DE]NAPHTHACENE-7-ONE

Condensation reaction of 7H-benzo[de]naphthacene-7-one (1 Kohno, Y., Kohno, M., Saito, Y. and Inokuchi, H. 1975. Crystal Structure of Tetrabenzo[a,cd,j,lm]perylene. Acta Cryst., B31: 2076–2080.  [Google Scholar]) was conducted in fused salt using zinc dust at 275°C for 2 h. The reaction products were isolated by column chromatography and then purified by recrystallization, yielding crystals of orange-yellow needles as the main product. This compound with an absorption maximum at 450 nm was identified as trinaphtho[2,3-c; 2′,1′,8′-fgh; 2″,1″,8″-uva]-pentaphene by one-dimensional and two-dimensional ¹H NMR spectroscopy, which was one of expected condensation products. We are now trying to isolate the other expected condensation products, benzo[vwx]dinaphtho[2,1-a; 8′,1′,2′-cde]hexaphene and benzo[cd]naphtho[2,3-f]anthra[3,2,1-lm]perylene, from the byproducts.     

Synthesis of 7H-Benzo [de] -s-triazolo [5,1-a] isoquinolin-7-one derivatives and study of their fluorescent properties

N-Aminonaphthalimide (4a) and N-amino-5-nitronaphthalimide (4b) prepared from acenaphthene (1a) and 5-nitroacenaphthene (1b) by oxidation, cyclization with acetic anhydride and subsequent treatment with hydrazine sulphate were reacted with a variety ofcarboxylic acid amides such as formamide, acetamide, benzamide, cinnamic amide, coumarin-3-carboxamide and urea using zinc chloride in ethanediol at 150°C to give the 10-substituted and 6-nitro-10-substituted-7H-benzo[de]-s-triazolo[5,1-a]-isoquinolin-7-ones (6a–6f and 6b–6m), respectively. Acetylation of the 10-amino derivative 6f and reductive acetylation of the 6-nitro-10-substituted derivatives 6h–6m gave the 10-acetamido, 6-acetamido-, 6-acetamido-10-methyl, 6-acetamido-10-phenyl, 6-acetamido-10-(2-styryl), 6-acetamido-10-(coumarin-3-yl) and 6,10-bisacetamido derivatives (6g, 7a–7f), respectively. The fluorescent properties of the compounds 6a–6e and 7a–7f were studied. Compounds 6a, 6b and 7e were applied as fluorescent whiteners on polyester fibres and gave satisfactory results.     

Synthesis and Dyeing Examinations of 7H, 9H-Quinazolino [3,2-b] benz [d,e] isoquinolin-7-one

The synthesis and application of a representative compound of the new group of disperse dyes derived from 7H,9H-quinazolino[3,2-b] benz[d, e] isoquinolin-7-one (II) have been investigated. The MS, IR and NMR spectra of compound (II) are analysed, and its dyeing and colour properties are compared with 7H-benzimidazo-[2,1-a] benz [d.e] isoquinolin-7-one (I).     

7-羟甲基咪唑并[1,2-a]吡啶的合成

以6-氨基-3-吡啶甲酸为起始原料,经过酯化反应、环合反应、还原反应得到7-羟甲基咪唑并[1,2-a]吡啶,总收率为42％.     

7-甲基-2-芳基-2H-吡唑[3,4-e]并-1,2,4-三嗪-3-醇的合成

以寻找干扰嘌呤核酸代谢的抗肿瘤新药为目的,设计合成了嘌呤生物碱类似物。以3-甲基-5-氨基-4H-吡唑为原料,经重氮化偶合、氨解、关环等反应合成了9种新的标题类化合物,通过元素分析、1HNMR和质谱分析确定其结构。     

[η]-M-Beziehung von Polyoctenameren

Solution properties of polyoctenamers were studied. A relation [η]-M in toluene at 25°C was elucidated. The k_θ-value derived from this relation agrees quite well with similar data of polybutadiene, polypentenamer and polyethylene. No evidence was found for the existence of cyclic structures in polyoctenamers.     

Condensation of 7 H -Benzo[ de ]naphthacene-7-one (9,10-Dibenzanthrone)

We have synthesized undecacyclic aromatic hydrocarbons using condensation of dibenzoanthrones. For example, dibenzo[ a,o ]dinaphtho[3,2,1- cd ;1,2,3- lm ]perylene, diphenanthra[1,2,3- cd ; 3,2,1- lm ]perylene and diphenanthra[2,3,4- cd ;4,3,2- lm ]perylene were produced from 5,6-, 8,9- and 10,11-dibenzoanthrones, respectively. In the present study, we have extended our work and aimed to synthesize new undecacyclic aromatic hydrocarbons by the use of 9,10-dibenzoanthrone (7 H -benzo[ de ]naphthacene-7-one) as a starting material. 9,10-Dibenzoanthrone was prepared by the cyclization of 1,2'-dinaphthylketone in aluminum chloride anhydride and sodium chloride, and the structure was confirmed by NMR measurements. It dissolves into ethanol and crystallizes in pale yellow needles; its melting point is 198.2-199.3°. The condensation of 9,10-dibenzoanthrone should give undecacyclic aromatic hydrocarbons such as benzo[ vwx ]naphtha[12,1,2- cde ] hexaphene.     

The enantiomers of 7aH-cyclopenta[b]pyran-7-ones and their thermal racemization

The separation of the enantiomers of 7aH-cyclo-penta[b]pyran-7-ones 1 was performed by enantioselective liquid chromatography with the sorbent/solvent systems triacetylcellulose/methanol, tribenzoylcellulose/methanol, and (+)-poly(trityl methacrylate)/silica gel/n-heptane/isopropanol. Barriers to ring opening were determined for two 7a-methyl and two 7a-phenyl substituted 2,4,5-triaryl derivatives by thermal racemization of the enantiomers. Substituted cyclopentadienones 2 are discussed as intermediates in the thermal electrocyclic ring opening/ring closure reactions.