甲酰基-8-羟基喹啉的合成

以8-羟基喹啉为原料,通过Reimer-Tiemann反应合成了5-甲酰基-8-羟基喹啉(收率15.0%)和7-甲酰基-8-羟基喹啉(收率21.5%),其结构经1HNMR和IR表征。     

7-硝基-8-羟基喹啉的合成

以8-羟基喹啉为原料,经硝化和脱磺酸基保护两步反应合成了7-硝基-8-羟基喹啉,总收率69％,纯度高于99％.其结构经1H NMR,13C NMR和HR-MS确证.     

天然5,7-二羟基-3-异戊烯基黄酮与5-羟基-3-异戊烯基黄酮的全合成

以2,4,6-三羟基苯乙酮和2,6-二羟基苯乙酮为原料, 分别通过甲基保护酚羟基、 苯甲酰氯酰化、 Bake-Venkataraman重排、 异戊烯基化、 酸催化关环及EtSLi脱去甲基等6步反应, 以高收率完成了天然5,7-二羟基-3-异戊烯基黄酮(1a, 收率80.6%)和5-羟基-3-异戊烯基黄酮(1b, 收率84.9%)的全合成, 所有化合物均经 ¹H NMR 和 ¹³C NMR表征确定. 通过密度泛函理论方法对目标产物(1a和1b)的生物活性进行了预测. 结果表明, 3位异戊烯基侧链的存在能大大增强化合物相应的生物活性, 而且是化合物生物活性增强必需的取代基. 另外, 目标产物1a的生物活性高于产物1b, 归因于黄酮类化合物分子中A环上的7-OH属增效基团, 起到增强生物活性的作用, 化合物1a分子中A环上有7-OH, 而化合物1b分子中则无该基团. 本合成方法对其它3-烃基黄酮类天然化合物的合成具有潜在的适用性, 所预测的生物活性结果为3-烃基黄酮类化合物的构效关系研究奠定了基础.     

1-羟基-1-甲基-3-氧-异吲哚类衍生物的合成

邻苯二甲酸酐与丙二酸反应合成邻乙酰基苯甲酸(1);1经酰氯化反应得邻乙酰基苯甲酰氯(2);2与伯胺反应合成了3个1-羟基-1-甲基-3-氧-异吲哚化合物,总收率65.0%～76.8%,其结构经1H NMR, 13C NMR, IR和MS表征.     

5-羟基-3,4-二氢异喹啉-1-酮的合成

以异喹啉为起始原料,经成盐、磺化得异喹啉-5-磺酸(3),3与熔融的氢氧化钠和氢氧化钾反应得1,5-二羟基异喹啉(4),以5%Pd-C为催化剂还原4得5-羟基-3,4-二氢异喹啉-1-酮(1),总收率47.6%。1的结构经1H NMR和MS确证。     

高纯度(>99%)6-羟基犬尿喹啉酸的合成

以丁炔二羧酸二甲酯和对氨基苯酚为原料,经迈克尔加成、环合和碱水解反应合成了6-羟基犬尿喹啉酸,总收率43.3%,纯度>99%,其结构经1H NMR,13C NMR和HR-MS确认。     

硫酸氢钠催化合成对羟基苯甲酸异丁酯

在一水硫酸氢钠存在下，异丁醇与对羟基苯甲酸发生酯化作用，高收率地合成了对羟基苯甲酸异丁酯。研究了一水硫酸氢钠用量、异丁醇用量和反应时间对羟基苯甲酸异丁酯收率的影响。当对羟基苯甲酸、异丁醇和硫酸氢钠的物质的量比为1：3：0.036，回流分水7h时，酯收率达99%。     

2-羟基-5,6,7,8-四氢-5,8-亚甲基喹啉-3-羧酸的合成

5,6,7,8-四氢喹啉及衍生物是医药和农药的重要中间体。2-羟基-5,6,7,8-四氢-5,8-亚甲基喹啉-3-羧酸是合成HIF脯氨酰羟化酶抑制剂的重要中间体,其合成方法目前无文献报道。本文以降冰片烯为起始原料,经水合、氧化、缩合、环合和水解5步反应合成目标产物,总收率43.09%,结构经¹H NMR、 ¹³C NMR和MS确证。该路线具有原料廉价易得、操作简单、后处理方便且收率较高等优点,适合工业化生产。     

加兰他敏重要中间体溴那维定的合成

以6-溴异香草醛和酪胺为原料,经一锅法进行连续的两步还原胺化制得N-甲基-N-(4-羟基苯乙基)-2-溴-5-羟基-4-甲氧基苯甲胺(4),收率85%。以5%聚乙二醇为相转移催化剂,氯仿为溶剂,铁氰化钾为氧化剂,对4进行氧化偶联,合成了加兰他敏的重要中间体溴那维定,收率39%,其结构经1H NMR,IR和MS确证。     

苄基异喹啉生物碱Neolitacumonine、Mollinedine和Papaverine的全合成

研究了苄基异喹啉生物碱的一条新的通用合成路线.其关键步骤为1-苄基-3,4-二氢异喹啉的铜催化氧化芳构化串联反应.以胡椒醛或3,4-二甲氧基苯甲醛为起始原料,经8步反应,分别以42%、37%和37%的总收率实现了三个苄基异喹啉生物碱Neolitacumonine、Mollinedine和Papaverine的全合成.     

手性杯[4]丝氨酸衍生物的合成及其催化性能

以对叔丁基苯酚为原料,经环化缩合、脱叔丁基、酚羟基醚化、甲酰化和氧化反应制得5-羧基-25,26,27,28-四正丙基杯[4]芳烃(5);5与O-苄基-N-苄氧羰基丝氨酸反应制得5-(O-丝氨酸)-25,26,27,28-四正丙基杯[4]甲酸酯(7),其结构经~1H NMR,~(13)C NMR和MS(ESI)表征。研究了溶剂和水的用量对7催化性能的影响。结果表明:水为溶剂,其用量为10 eq.时,收率和非对映选择性分别为95%和3∶97 dr;当水的用量为30 eq.时,收率和非对映选择性分别为93%和98∶2 dr。     

An unexpected ring-opening in the reissert reaction on 2,3-diphenylquinoxaline-n-oxide.

When quinoxaline-N-oxide 1 is reacted with KCN and benzoyl chloride in water (the Reissert reaction) or methanol, the products are 2-,5- and 6- chloroquinoxaline (the latter being the major product: 42±6 %) and small amounts of 2-cyanoquinoxaline. Using three equivalents of trimethylsilyl cyanide instead of KCN, and dichloromethane as the solvent, leads to a 72 % yield of 2-cyanoquinoxaline. The reaction of trimethylsilyl cyanide and benzoyl chloride with 2,3-diphenylquinoxaline-N-oxide 2 leads to an unexpected ring-opening product 13; its structure is based on spectroscopic data and on an X-ray crystallographic analysis.     

Chemistry of thienopyridines. XLII. Three novel compounds derived from thienopyridine N-oxides

Extension of the Reissert-Henze reaction to treatment of thieno[2,3-b]pyridine 7-oxide with potassium thiocyanate and benzoyl chloride in water-methylene chloride gives a 2% yield of bis(6-thieno[2,3-b]pyridyl) disulfide. Peroxidation of 5-ethylthieno[2,3-b]pyridine ( 4 ) forms the 7-oxide 5 (53%), converted to a monopicrate 5a . Picrate 5a undergoes N-deoxygenation to 4 -picrate on drying at 78° in vacuo, but shows the expected additive mass spectrum of 5 (thermally stable) and picric acid. Nucleophilic displacement of chloride ion from 7-chlorothieno[3,2-b]pyridine (derived, in turn, from thieno[3,2-b]pyridine 4 -oxide) by the anion from ethyl cyanoacetate gives 7-(1-cyano-1-ethoxycarbonyl)methylene-4,7-dihydrothieno[3,2-b]pyridine (82%), stable in this iminodienic tautomeric form.     

Preparation and reactions of 1,3-diphosphacyclobutane-2,4-diyls that feature an amino substituent and/or a carbonyl group

The preparation and properties of a 1-amino-1,3-diphosphacyclobutane-2,4-diyl and a 1-benzoyl-1,3-diphosphacyclobutane-2,4-diyl, which can be regarded as functionalized cyclic biradical derivatives, were investigated. Hydrolysis of 1-diisopropylamino-3-methyl-2,4-bis(2,4,6-tri-tert-butylphenyl)-1,3-diphosphacyclobutane-2,4-diyl (7), which is formed by reaction of Mes*C[triple chemical bond]P (4; Mes*=2,4,6-tBu(3)C(6)H(2)) with lithium diisopropylamide and iodomethane, resulted in ring-opening of the 1,3-diphosphacyclobutane-2,4-diyl skeleton, as well as de-aromatization of one of the Mes* rings. 3-Oxo-1,3-diphosphapropene 8 and 7-phosphabicyclo[4.2.0]octa-1(8),2,4-triene 9 were the resultant products, and these were subsequently characterized. Isomerization and oxidation of 7 occurred in the presence of TEMPO (2,2,6,6-tetramethyl-1-piperidinoxy) to give the first example of a cyclic dimethylenephosphorane derivative, namely 3-oxo-1,3-diphospha-1,4-diene 10. 1-Benzoyl-3-tert-butyl-2,4-bis(2,4,6-tri-tert-butylphenyl)-1,3-diphosphacyclobutane-2,4-diyl (12) was isolated and characterized from the reaction of 4 with tert-butyllithium and benzoyl chloride. Compound 12 was subsequently heated and underwent rearrangement of the benzoyl group and ring-expansion to afford 1-oxo-1H-[1,3]diphosphole 13. Reaction of 4 with lithium diisopropylamide and benzoyl chloride afforded the 2H-[1,2,4]oxadiphosphinine 15, which was probably formed through the 1,3-diphosphacyclobutane-2,4-diyl intermediate 14. Thermolysis of 15 afforded 1-oxo-1H-[1,3]diphosphole 16 in an Arbuzov-type rearrangement.     

达比加群酯中间体3-【【【2-{[(4-氰基苯基)氨基]甲基}-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸乙酯的合成

以对氨基苯腈为起始原料,经胺化反应制得N-(4-氰基苯基)甘氨酸(4);4与N-[3-氨基-4-(甲基氨基)苯甲酰基]-N-2-吡啶-β-丙氨酸乙酯(5)经酰胺化后经闭环反应,合成了达比加群酯的关键中间体——3-【【【2-{[(4-氰基苯基)氨基]甲基}-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸乙酯,总收率79.6%,其结构经~1H NMR和ESI-MS确证。     

An unusual reaction of 2-(2-pyridylcarbonyl)- and 2-(2-quinolylcarbonyl)benzoyl chlorides with p-nitroaniline

In the reaction of 2-(2-pyridylcarbonyl)benzoyl chloride, which exists in the form of 6,11-dioxo-6,11dihydrobenzo[b]quinolizinium chloride, with p-nitroaniline, 2-(4-nitrophenylimino)-6, 11-dihydro-2H-benzo-[b]quinolizine-6, I I -dione is unexpectedly formed. When it reacts with water or methanol there is an opening of the quinolizine ring and aromatization of the quinoid fragment with the formation of 2-[4-(4nitrophenylamino)-2-pyridylcarbonyl]benzoic acid or its methyl ester. Under the action of antimony pentachloride, 2- 2-quinolylcarbonyl)benzoylchloride-3 (2-quinolyl)-3-chloro- 1, 3-dihydrobenzo[c]furan-1 -one -is converted to 3-(2-quinolyl)-1,3-dihydrobenzo[c]furan-1-on-3-ylium hexachlorantimonate, which undergoes isomerizing recyclization upon heating to 7,12-dioxo-7,12-dihydrobenzo[b/ hexachloroantimonate. The latter enters into an analogous reaction with p-nitroaniline, thereby forming 5-(4-nitrophenylimino)-7,12-dihydro-5H-dibenzo[b,f]quinolizine-7,2-dione.Riga Technical University, Riga LV-1048. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 938–944, July, 1995. Original article submitted May 31, 1995.     

Synthesis and characterization of benzyl and benzoyl substituted oxime-phosphazenes

Two oxime-cyclophosphazenes were prepared from hexakis(4-formylphenoxy)cyclotriphosphazene (2) and hexakis(4-acetylphenoxy)cyclotriphosphazene (7). The reactions of these oximes with benzyl chloride, benzenesulfanoyl chloride, benzoyl chloride, 4-methoxybenzoyl chloride and 2-chlorobenzoyl chloride were studied. Hexa and pentasubstituted compounds were obtained from the reaction of hexakis(4-[(hydroxyimino)methyl]phenoxy)cyclotriphosphazene (3) with benzyl chloride (4) and benzoyl chloride, respectively. However, the oxime groups on 3 rearranged to nitrile (5) in the reaction of 3 with benzenesulfanoyl chloride and 1-napthalenesulfanoyl chloride. Hexasubstituted compounds were also obtained from the reactions of hexakis(4-[(1)-N-hydroxyethaneimidoyl]phenoxy)cyclotriphosphazene (8) with benzoyl chloride (10), 4-methoxybenzoyl chloride (11) and 2-chlorobenzoyl chloride (12). A trisubstituted compound was obtained from the reaction of 8 with benzyl chloride (9). All the products were generally obtained in high yields. Pure and defined products could not be obtained from the reaction of 3 with 4-methoxybenzoyl chloride and 2-chlorobenzoyl chloride. The structures of the compounds were defined by elemental analysis, IR, ¹H, ¹³C and ³¹P NMR spectroscopy.     

[60]Fullerene diol issued from pentaerythritol derivatives

A new [60]fullerene diol is synthesized in good yield, in two steps starting from reaction of C₆₀²⁻ anion with the benzylideneacetal derived from 2,2-bis(iodomethyl)-1,3-propanediol. The corresponding [60]fullerene bis-mesylate is also formed in a similar way starting from bis-iodo bis-mesylate compound in the same series. The scope of this fullerene diol in synthesis is exemplified by its easy esterification with 4-formyl benzoyl chloride.     

正十六烷基磺酰氯的合成

正十六烷醇经亚磺酰甩作用转换成1－氯代正十六烷,在相转移催化剂条件下,1－氯代正十六烷和硫脲进行亲核反应,合成正十六烷基异硫脲盐酸盐,并以此为中间体用氯气氧化法制备正十六烷基磺酰氯,纯度大于95％,总收率为67％。     

含吡啶环的N-(1,3,4-噻二唑-2-基)苯甲酰胺类化合物的合成及其抑菌活性

以3-吡啶乙酸盐酸盐与氨基硫脲为原料经环化反应制备中间体2-氨基-5-(3-吡啶亚甲基)-1,3,4-噻二唑,后者与取代苯甲酰氯反应合成了一系列含吡啶环的N-(1,3,4-噻二唑-2-基)取代苯甲酰胺(3a~3k),其结构通过IR、~1H NMR、~(13)C NMR、MS和元素分析确证。用菌丝生长速率法测定了目标化合物对灰霉菌的离体抑菌活性,结果表明,部分化合物对病原菌有一定的抑制活性。