Syntheses of 3-Acyl-4-hydroxy-2(1H)quinolones

3-Acyl-4-hydroxy-2(1H)-quinolones 5 are obtained by hydrolytic ring opening and subsequent decarboxylation from the corresponding pyrano[3,2-c]quinolin-2,5(6H)-diones 4 , which in turn are easily obtained from 1:2 condensation of anilines 1 with diethyl malonate 2a or 1:1 condensation of diethyl alkyl- or arylmalonates 2b–e with 4-hydroxy-2(1H)-quinolones 3 . Nitropyranoquinolinediones 6 furnish after ringopening 3-nitroacetyl-4-hydroxy-2(1H)quinolones 8 . Pyranoquinolines 7 and 9 with acetyl- or aminosubstituents are hydrolyzed during basic ringopening to yield 5 .     

3-(2-氟-4-氯-5-甲氧羰基乙巯基苯基)-5-异丙叉基恶唑烷-2,4-二酮的合成

通过2-氟-4氯-5甲氧羰基乙巯基苯基异氰酸酯与2—羟基—3—甲基—3—丁烯酸乙酯发生加成、闭环反应制得除草剂3—(2—氟-4氯—5—甲氧羰基乙巯基苯基)—5-异丙叉基噁唑烷—2，4-二酮，优化反应条件为n(异氰酸酯)：n(2—羟基—3—甲基—3—丁烯酸乙酯)＝1：1．25—1：1．30。     

Synthesis of pyrazolo[4′,3′:5,6]pyrido[1,2-a]benzimidazole derivatives and study of their fluorescence properties

Synthesis of pyrazolo[4′,3′ :-5,6′pyrido]1,2-a benzimidazoles was achieved by the condensation of 1-chloro-2-formyl-3-methyl pyrido[1,2-a]benzimidazole-4-carbonitrile and 1-chloro-3-methyl pyrido[1,2-a]benzimidazole-2,4-dicarbonitrile with hydrazine hydrate and phenyl hydrazine. The fluorescence properties of the resulting compounds were studied. Some of the compounds when applied on polyester fibres as fluorescent brighteners gave excellent results.     

新除草剂RZH-01-004的合成及除草活性

通过7-氯-5-氟4异氰酸酯基-2,2-二甲基-2,3-二氢-1-苯并呋喃和2-羟基-甲基-3-丁烯酸乙酯发生加成环化反应制得除草剂3-（7-氯-5-氟-2,2-二甲基-2,3-二氢-1-苯并呋喃-4-基）-5-（1-甲基亚乙基）-1,3-噁唑烷．2,4-二酮,收率70％,含量97.8％。产品结构用CIMS,HNMR进行了确定。室内生测结果表明,RZH-01-004苗后茎叶处理对大多数阔叶杂草有较高的除草活性。     

Disperse Dyes Derived from 4-Phenylazo-1-naphthylamine and 4-Phenylazo-5-hydroxy-1-naphthylamine

Application of the Bucherer reaction between 1-naphthol and alky lamines gave a satisfactory synthesis of N-substituted 1-naphthylamines. A method avoiding the use of pressurised reaction vessels, i.e. reaction of 1-naphthol with alkylamines in the presence of zinc chloride and hydrochloric acid, is reported. Coupling of diazotised 6-chloro-2,4-dinitroaniline to the above intermediates affords blue dyes which colour synthetic-polymer fibres in deep shades of generally good fastness to light and sublimation. Similar use as coupling components of 5-hydroxy-1-naphthylamines enables blue dyes to be obtained without the use of trisubstituted anilines as diazo component. Dyes thus derived from 2-chloro-2-nitroaniline absorb at longer wavelength than those from 6-chloro-2,4-dinitroaniline with analogous 1-naphthyl-amine-based couplers. Similar bathochromic shifts are observed in dyes derived from 2-methoxy-1-naphthylamines as coupling components, but these dyes have poor stability. Relationships between colour and dye structure are reported, and the use of 4-amino-1,8-naphthalimides as diazo components was additionally investigated. These give, with N-substituted 1-naphthylamines as coupling components, deep bluish-violet dyes of good fastness properties.     

Ring closure reaction of 5-hydroxy-pyrido[2,3-d]pyrimidine-2,4,7-triones to benzo[b]pyrimido[4,5-h]1,6-naphthyridine-1,3,6-triones

N-Substituted aminouracils ( 1 ) react with malonates by cyclocondensation to 5-hydroxy-pyrido[2,3-d]pyrimidine-2,4,7-triones ( 2 ), which give with triethylorthoformate and aniline 6-(phenylaminomethylene)-pyrido[2,3-d]pyrimidine-tetraone ( 3 ). Halogenation of 2a - d (with R² = Me) with phosphorylchloride leads to 5,7-dichloro-pyrido[2,3-d]pyrimidine-2,4-diones ( 4 ) by cleavage of the methyl group at N-8, whereas Vilsmeier reaction of 2 affords 5-chloro-6-formyl derivatives ( 6 ), which cyclize with arylamines to give benzo[b]pyrimido[4,5-h] 1,6-naphthyridines ( 9 ). Compounds 9 were obtained independently by amination of the tosylates 5 to the 5-arylamino compounds 8 , and Vilsmeier formylation to yield 9 .     

The chlorination of 1,4-dihydroxyanthraquinone with thionyl chloride

The chlorination of 1,4-dihydroxyanthraquinone (quinizarin) using thionyl chloride yielded three different products, depending on the purity of the starting material and catalysts used. The compounds isolated were 9-chloro-10-hydroxy-1,4-anthraquinone (3a), 2,4-dichloro-1-hydroxy-anthraquinone (2) and the new compound 1-hydroxy-4-(4-hydroxy-anthraquinone-1-oxy)-anthraquinone (4a). Some acylated derivatives of 3a and of 4a are reported.     

Synthese von Glutaconaldehyden aus Quadratsäure-Pyridiniumbetainen

Synthesis of Glutaconaldehydes from Pyridinium Betaines of Squaric Acid The pyridinium ring of squaric acid betaines ( 2 ) is opened by hydroxide ions. Electronegative substituents (RCl, CN) at C-3 promote this reaction. The stereochemistry of the resulting 5-(2-hydroxy-3,4-dioxocyclobut-1-en-1-yl)aminopenta-2,4-dienales ( 3 ) is confirmed by NMR-spectroscopy. Treatment of 3 with sodium hydroxide results in further hydrolysis to the sodium salts of glutaconaldehydes ( 5 ) and 3-amino-4-hydroxycyclobut-3-ene-1,2-dione ( 6 ). These products are also directly obtained from the nicotinic acid derivates 2 d (RCOOEt) and 2 e (RCONH₂), in the latter case cyclisation of the glutaconic acid derivate to the known 3-formylpyrid-2-one ( 10 ) is observed.     

Studies on the Vilsmeier-haack reaction. Part XIII: Novel heterocyclo-substituted 4,4′-bi-pyrazolyl dithiocarbamate derivatives

5-Imino-3-methyl-l-phenyl-2-pyrazoline-4-dithiocarbamic acid (I) underwent simultaneous formylation and dimerization reactions with the Vilsmeier reagent giving 4-[5′-imino-3-(1″-formyl-2″-dimethylaminoethenyl)-3′-methyl-1′-phenyl-1′H-pyrazolo-4′-dithiocarbamyl-2,4-dihydro-3-imino-5-methyl-2-phenyl-1-pyrazoline]dithiocarbamate (II) which hydrolysed with sodium hydroxide to give 4-[3′-(1″-formyl-2″-hydroxyethenyl)-3′-methyl-1-phenyl-1′-H-pyrazolo-4′-dithiocarbamyl-1′-pyrazoline]dithiocarbamate-5,5′-dione (IV). Treatment of II and/or IV with morpholine, piperidine, piperazine, hydroxylamine, hydrazine hydrate or phenylhydrazine afforded the corresponding dipyrazolo-4,4′-dithiocarbamate derivatives with different heterocyclic systems at the 3-position. The structures of these compounds were confirmed by microanalysis data, IR and ¹H-NMR spectrometry. All synthesized compounds have been screened in vitro against Gram-positive and Gram-negative bacteria, and fungi.     

泛昔洛韦的合成

以2-氨基-6-氯嘌呤(2)为原料,在相转移催化剂四丁基溴化铵催化下与3-溴丙烷-1,1,1-三甲酸乙酯(3)缩合,得2-氨基-6-氯-9-(2,2-二乙氧羰基丁酸乙酯-4-基)嘌呤(4)。4用乙醇钠溶液脱羧得2-氨基-6-氯-9-(2-乙氧羰基丁酸乙酯-4-基)嘌呤(5)。5在AlCl3催化下,用NaBH4作还原剂还原得2-氨基-6-氯-9-(4-羟基-3-羟甲基丁基)嘌呤(6)。6在4-二甲基氨基吡啶(DMAP)催化下,与醋酐反应得2-氨基-6-氯-9-(4-乙酰氧基-3-乙酰氧基甲基丁基)嘌呤(7)。7在Pd-C催化下,氢化脱氯得泛昔洛韦(1)。以2-氨基-6-氯嘌呤(2)计总收率为55%。     

3-(4-氯-5-环戊氧基-2-氟苯基)-4-亚胺基-5-异丙叉基恶唑烷-2-酮的合成

通过 4 氯 5 环戊氧基 2 氟异氰酸苯酯与 2 羟基 3 甲基 3 丁烯腈发生加成环化反应制得除草剂 3 (4 氯 5 环戊氧基 2 氟苯基 ) 4 亚胺基 5 异丙叉基恶唑烷 2 酮。反应分两阶段进行 ,首先在冰水浴中向 2 羟基 3 甲基 3 丁烯腈中滴加 4 氯 5 环戊氧基 2 氟异氰酸苯酯甲苯溶液 ,然后升至室温反应 4h。优化的反应条件为 :三乙胺作催化剂 ,n(4 氯 5 环戊氧基 2 氟异氰酸苯酯 )∶n(2 羟基 3 甲基 3 丁烯腈 ) =1 0∶1 2 ,加料方式为滴加 4 氯 5 环戊氧基 2 氟异氰酸苯酯甲苯溶液 ,第二阶段反应在室温下进行。反应条件优化以后 ,产品收率可由 39%提高到 5 6 %。产品结构用CIMS、1HNMR进行了确定。分离了其中一个副产物 ,并对其结构进行了鉴定。     

南海红树林内生真菌ZH-3代谢产物研究

研究南海红树林内生真菌ZH-3的代谢产物。采用反复硅胶柱色谱法、Sephadex LH-20凝胶色谱法等进行分离纯化,并通过理化常数测定和光谱分析鉴定其化学结构。从南海红树林内生真菌ZH-3的菌体中分离得到4个代谢产物,经波谱解析,分别为2-（3-chloro-2,6-dihydroxy-4-methylbenzoyl）-5-hydroxy-3-methoxybenzoate.（1）,3＇-dihydroxy-5,5＇-dimethyldiphenyl ether（2）,7,8-二甲基苯并[g]蝶啶-2,4（1H,3H）-二酮（3）,5-o-methylbostrycoidin （4）。初步药理活性显示化合物1对人体肝癌细胞hepG2抑制的IC50值为25μg·mL-1。所有化合物均首次从南海红树林内生真菌ZH-3中分离得到。     

沙奎那韦中间体合成工艺改进

治疗艾滋病的沙奎那韦的中间体———(3S,4 aS,8 aS)-2〔-(2R,3S)-3氨-基-2羟-基-4苯-基丁基〕-N-叔丁基-十氢异喹啉-3-羧酰胺(Ⅱ)是通过(2S,3S)-4氯--3羟-基-1苯-基丁烷-2氨-基甲酸苄酯(Ⅲ)和(3S,4 aS,8 aS)-N-叔丁基-十氢异喹啉-3-羧酰胺(Ⅴ)反应得到的。该文对工艺进行了如下改进:Ⅲ的环化和与Ⅴ的反应合并为“一锅煮”工艺,去除原有文献报道的柱层析过程,只需洗去氢氧化钾的分液操作,直接加入w(Pd)=10%的Pd/C催化剂,室温反应12 h即脱去保护基。反应完毕后,以乙腈重结晶即得到目标产物Ⅱ。改进后的工艺总产率达到87%,w(Ⅱ)=98.5%。该法原则上适用于多种H IV蛋白酶抑制剂的合成。     

Synthesis of 1,2-fused benzimidazo heterocycles from benzimidazole-2-acetonitrile and heterocyclic ortho-chloroaldehydes

The condensation of 5-chloro-4-formyl-3-methyl-1-phenylpyrazole with benzimidazole-2-acetonitrile led to the formation of the fused heterocycle 3-methyl-1-phenyl-1H-pyrazolo [4,3:5,6]pyrido[1,2-a]benzimidazole-5-car-bonitrile. Similar condensation of 2-chloro-3-formylquinoline derivatives gave the corresponding 1,2-fused benzimidazo heterocycles. These heterocycles underwent oxidative cyanation.     

Synthesis and bacteriostatic properties of acylarylureas and alkylarylureas

Fatty substituted ureas (RNHCONHR’) were prepared where R is an aliphatic acyl or alkyl group and R’ is a substituted phenyl group or a thiazole group. The benzene ring was generally substituted with chlorine, nitro, hydroxy, or a combination of these groups. The compounds were ineffective against gram-negative microorganisms but a number of samples inhibited the growth ofStaphylococcus aureus at 1 ppm. Bacteriostatic activity was generally observed where the acyl or alkyl group contained 6–10 carbon atoms and where R’ is 4-nitrophenyl, 4-chloro-3-nitrophenyl or a thiazole group derived from 2-amino-5-nitrothiazole. Scattered activity at 1 ppm was observed where R’ is 3-nitrophenyl, 2,4- and 3,5-dichlorophenyl, 2-hydroxy-5-chlorophenyl, 2-hydroxy-5-nitrophenyl, 3-nitro-4-hydroxyphenyl, 3,5-dinitrophenyl and 2-nitro-4-chlorophenyl. The alkylureas appear to be more active than the acylureas.     

相转移催化条件下的4-氯-2-氟苯肼的合成

以4-氯-2-氟苯胺为原料,冰乙酸为助溶剂,PEG-400相转移催化作用下进行重氮化反应,再经过还原、酸析、碱解等三步反应制备出目标化合物,产率≥74.0%.考察了催化剂用量、还原温度、酸析温度对反应收率的影响,适宜的反应条件是:重氮化、还原、酸析的反应温度分别为0℃、75℃、85℃.物质量的比为n(4-氯-2-氟苯胺...     

基于四甲基久洛尼定为原料的香豆素衍生物的合成

以间氨基苯酚和溴代异戊烯为起始原料经过亲核取代制备了N,N-二(3-甲基-2-丁烯)-3-羟基苯胺氢溴酸盐,通过亲电取代关环合成了8-羟基-1,1,7,7-四甲基久洛尼定,再经Vilsmeir-Haack反应引入醛基获得了9-甲酰基-8-羟基-1,1,7,7-四甲基久洛尼定,总收率为25.7%。对N,N-二(3-甲基-2-丁烯)-3-羟基苯胺氢溴酸盐的合成进行了工艺探索,结果表明当间氨基苯酚和溴代异戊烯投料比为1:2,CaCO3为缚酸剂时得到的收率较佳。以9-甲酰基-8-羟基-1,1,7,7-四甲基久洛尼定为原料,分别与噻吩乙腈、对溴苯乙腈进行缩合反应制备得到3-芳基香豆素衍生物,对其结构进行了核磁鉴定,并对其紫外光谱进行了测试。     

β-Cyclodextrin Based Molecularly Imprinted Solid Phase Extraction for Class Selective Extraction of Priority Phenols in Water Samples

Molecular imprinted polymer (MIP MAA-β-CD) with 2,4-dichlorophenol (2,4-DCP) and methacrylic acid functionalized β-cyclodextrin (MAA-β-CD) as the template molecule and the functional monomer, respectively, was prepared and used in molecular imprinted-solid phase extraction (MISPE) for the extraction of phenols (2,4-dichlorophenol, 2-chlorophenol, 4-chloro-3-methylphenol, 4-chlorophenol, 2,4,6-trichlorophenol, and 2-nitrophenol) from water samples. The MISPE method was optimized prior to the determination using gas chromatography coupled with a flame ionization detector (GC-FID). Under the optimized conditions, the MIP MAA-β-CD sorbent showed good linearity (0.01-12 mgL^?1), low limits of detection (0.14-0.75 µgL^?1), and good repeatability (RSD 2.3-3.6%, n = 3). Good recoveries were obtained in the range of 97-115% for tap water and between 88-103% for river water. The developed MIP MAA-β-CD SPE was then compared with other adsorbents. The unique properties of β-CD and presence of imprinted cavities explains the higher extraction recoveries obtained for phenols when using MIP MAA-β-CD SPE.     

Synthesis and electronic spectra of 3-hetaryl substituted coumarin derivatives 7-hydroxy-2H-chromen-2-on and 9-hydroxy-2H-benzo(f)chromen-2-on

The synthesis of 3-hetaryl substituted coumarin derivatives [7-hydroxy-2H-chromen-2-on and 9-hydroxy-2H-benzo(f)chromen-2-on] containing a hydroxyl group by reacting 2,4-dihydroxybenzaldehyde and 2,4-dihydroxynaphtaldehydes with 2-cyanomethylbenzothiazole, 2-cyanomethylbenzimidazole, 1-methyl-2-cyanomethylbenzimidazole and 2-cyanomethyl-4-phenylthiazole is presented. The absorption and steady-state fluorescence characteristics of the synthesised 3-hetaryl substituted 7-hydroxy-2H-chromen-2-on and 9-hydroxy-2H-benzo(f)chromen-2-on in a solution of ethanol and at different pH values are studied to assess their possible application as fluorescent probes for use in molecular biology and medicine.     

6-Substituierte 2,4-Diphenyl-1,3,4-oxadiazin-5-one

6-Substituted 2,4-diphenyl-1,3,4-oxadiazin-5-ones By reaction of dichloro acetylchloride and β-N-phenyl benzhydrazide 6-chloro-1,3,4-oxadiazin-5-one 2 is accessible which reacts with potassium phthalimide and potassium succinimide, respectively, to from 6-phthalimido- and 6-succinimido 2,4-diphenyl-1,3,4-oxidiazinon ( 3 and 4 ), respectively. The phthalimido substituent can be substituted by benzylamine or hydrazine.