5-烷氧基-3,4-二卤-2(5H)-呋喃酮与不饱和胺的反应研究

为了深入探索5-烷氧基-3,4-二卤-2(5H)-呋喃酮与胺类试剂发生的反应,进一步在氟化钾作催化剂和四氢呋喃作溶剂的条件下,研究了其与系列不饱和胺的反应,通过旋光度,UV-Vis,IR,1H NMR,13C NMR,MS,元素分析和X射线单晶衍射等表征方法对产物进行结构表征,发现大多数情况下发生预期的串联迈克尔加成-消除反应,得到了16个新的β-胺基-2(5H)-呋喃酮化合物.当不饱和胺为空间位阻较大的2,5-二甲基-3-吡咯啉时,与位阻较大的5-孟氧基-3,4-二卤-2(5H)-呋喃酮反应只是生成异常的2(5H)-呋喃酮开环产物,而与位阻较小的5-甲氧基-3,4-二卤-2(5H)-呋喃酮反应则既有正常的β-胺基-2(5H)-呋喃酮产物,也有经开环重排反应的机理得到的异构体产物.后者表明,底物的位阻大小也是影响反应的因素,甚至导致同时存在竞争反应.     

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%.     

5-烷氧基-3,4-二卤-2(5H)-呋喃酮与脂肪胺类的反应研究

在氟化钾作催化剂和四氢呋喃作溶剂的条件下,研究了系列脂肪胺亲核试剂与5-烷氧基-3,4-二卤-2(5H)-呋喃酮发生的反应,通过旋光度,UV-Vis,IR,1H NMR,13C NMR,MS,元素分析和X射线单晶衍射等表征方法对产物进行结构表征,发现通常情况下发生预期的串联迈克尔加成-消除反应,合成了13个新的β-胺基-2(5H)-呋喃酮.但是,空间位阻较大的二环己基胺与5-烷氧基-3,4-二卤-2(5H)-呋喃酮反应时,却得到了4个异常的2(5H)-呋喃酮开环产物,其可能是经开环重排反应的机理得到的.     

5-(S)-烷氧基-3，4-二卤-2(5H)-呋喃酮在二甲基甲酰胺中的Michael加成-消除反应

5-羟基 - 2 (5H) -呋喃酮是一些具有生理活性天然产物的重要结构组份 [1] ,γ-内酯类的结构片段在一些抗病毒药物或前体结构中也常出现 ,由于内酯环的立体构型与药物的生物活性密切相关 ,因此它的合成具有十分重要的价值[2 ] .近年来利用天然手性助剂薄菏醇和冰片等的手性 5-烷氧基 - 2 (5H) -呋喃酮合成天然产物已引起人们的广泛关注 [1,3～ 13] .我们在研究手性 5-烷氧基 - 3,4-二卤 - 2 (5H) -呋喃酮 (4a_ 4 d)与 Wittig- Horner试剂 (O,O-二乙氧基丙酮基膦酸二乙酯 ) (5)的反应时 ,当以 DMF为溶剂 ,金属钠为催化剂时 ,并未得到目标…     

3-卤-4-脂肪胺基-5-联苯氧基-2(5H)-呋喃酮的合成

以硫酸为催化剂,4-羟基联苯与粘卤酸在甲苯溶剂中回流,经脱水醚化反应合成了3,4-二卤-5-联苯氧基-2(5H)-呋喃酮化合物.以这2个新型的中间体与不同的代表性脂肪胺类在KF催化的室温条件下,通过串联的迈克尔加成-消除反应,得到了16个新的3-卤-4-脂肪胺基-5-联苯氧基-2(5H)呋喃酮化合物,产率43%~79%(大部分55%以上).新化合物的结构经FTIR、UV、~1H NMR、~(13)CNMR、MS和元素分析确证.     

水介质中吡喃并[3,2-c]吡喃-5-酮衍生物的三组分一锅合成

水介质中在氯化三乙基苄基铵(TEBAC)催化下, 芳醛与丙二腈和4-羟基-6-甲基吡喃-2-酮三组分一锅反应合成了一系列2-氨基-3-氰基-4-芳基-4H,5H-吡喃-5-酮. 该反应具有产率高、污染少、操作简单、环境友好等优点.     

5-取代-3,4-二卤-2(5H)-呋喃酮的Sonogashira偶联反应

以5-取代-3,4-二卤-2(5H)-呋喃酮为底物进行Sonogashira偶联反应, 考察了反应温度、反应时间、钯催化剂种类与用量、碱种类与用量、溶剂、底物结构等对偶联反应的影响, 合成了28种新的2(5H)-呋喃酮衍生物, 其结构用IR, ¹H NMR, ¹³C NMR, MS和元素分析等方法进行了表征. 在优化的反应条件下, 即反应溶剂为甲苯、催化剂为3 mol% Pd(PPh₃)₄和10 mol% CuI、碱为6 equiv. KF、反应时间72 h、反应温度30 ℃时, 反应产率42%～84%. 利用该Sonogashira偶联反应合成新型的多官能团烯二炔结构化合物, 不仅合成途径简捷、反应条件温和, 绝大部分反应产率中等以上, 而且无需额外加入配体, 适用于芳香的和脂肪的末端炔烃.     

5-(S)-孟氧基-3,4-二卤-2(5H)-呋喃酮与4-硝基邻苯二胺的Michael加成―消除反应

在Et3N作为碱的温和条件下,5-(S)-孟氧基-3,4-二卤-2(5H)-呋喃酮与芳香胺4-硝基邻苯二胺发生串联的Michael加成―消除反应,生成了新的含有苯环结构的5-孟氧基-4-氨基-3-卤-2(5H)-呋喃酮类化合物。新化合物的结构通过紫外―可见光谱(UV-Vis)、红外光谱(IR)、质谱(MS)、核磁共振氢谱(1H NMR)、核磁共振碳谱(13C NMR)和元素分析等表征证实。该多环结构卤代2(5H)-呋喃酮化合物的合成,能为某些多官能团的结构复杂的2(5H)-呋喃酮化合物的合成提供新途径。     

(1R,4S,5S)-6-环己基-4-[(1R,2S,5R)-5-甲基-2-异丙基环己氧基]-3-氧杂-6-氮杂双环[3.1.0]-2-己酮的合成及结构表征

环已胺与差向异构体5-[(1R,2S,5R)-5-甲基-2-异丙基环己氧基]-3-溴-2(5H)-呋喃酮发生不对称Mi-chael加成-分子内亲核取代反应,并经柱层析分离,得到一对手性氮杂环丙烷-丁内酯衍生物,其中的标题化合物为首次得到的新手性化合物,产率17%,其结构经IR、1H NMR、13C NMR和HRMS进行了表征。     

含联苯醚结构2(5H)-呋喃酮衍生物的合成

以硫酸为催化剂,不同4'-烷氧基-4-羟基联苯与粘卤酸在甲苯溶剂中回流,经脱水醚化反应合成了16个新型的5-(4'-烷氧基-4-联苯氧基)-3,4-二卤-2(5H)-呋喃酮化合物,产率30%~58%(大部分47%以上).中等产率可能与该酸催化的反应为SN2亲核取代反应有关.新化合物的结构经FTIR,UV,1H NMR,13C NMR和元素分析确证.这些具有不同生物活性基团化合物的设计与合成,为新型2(5H)-呋喃酮衍生物的合成,以及由不同羟基化合物合成芳香醚类化合物提供了参考.     

Preparation of 7-hydroxy-2-oxoindolin-3-ylacetic acid and its [13C2], [5-n-3H], and [5-n-3H]-7-O-glucosyl analogues for use in the study of indol-3-ylacetic acid catabolism

An improved synthesis of 7-hydroxy-2-oxoindolin-3-ylacetic acid via the base-induced condensation reaction between oxalate esters and 7-benzyloxyindolin-2-one is described. 7-Benzyloxyindolin-2-one was prepared in four steps and 50% overall yield from 3-hydroxy-2-nitrotoluene. The yield of the title compound from 7-benzyloxyindolin-2-one was 56%. This route was used to prepare 7-hydroxy-2-oxoindolin-3-yl[13C2]acetic acid in 30% yield from [13C2]oxalic acid dihydrate. The method could not be extended to the preparation of the corresponding [14C2]-compound. However, an enzyme preparation from Zea mays roots catalysed the conversion of carrier-free [5-n-3H]indol-3-ylacetic acid with a specific activity of 16.7 Ci mmol-1 to a mixture of 7-hydroxy-2-oxo[5-n-3H]indolin-3-ylacetic acid and its [5-n-3H]-7-O-glucoside in ca. 3 and 40% radiochemical yield respectively. The glucoside was converted into the 7-hydroxy compound in 80% yield by means of beta-glucosidase.     

2,6,7-Trihydroxy-4,9-dioxodeca-2,5,7-trienoic and 2-hydroxy-2-(3-hydroxy-4-methyl-2,5-dioxocyclopent-3-en-1-ylidene)acetic acid esters: Synthesis and structural specificity

Claisen condensation of acetone and butan-2-one with diethyl oxalate in the presence of metallic sodium leads to the formation of ethyl 2,6,7-trihydroxy-4,9-dioxodeca-2,5,7-trienoate and ethyl 2-hydroxy-2-(3-hydroxy-4-methyl-2,5-dioxocyclopent-3-en-1-ylidene)acetate, respectively.     

A new synthesis of dibenzo[b,g][1,5]naphthyridine-6,12(5H,1H)dione (epindolidione)

A new convenient synthesis of dibenzo[b,g][1,5]naphthyridine-6,12(5H,11H)dione starting from N-phenylglycine ethyl ester is described. Ester condensation of N-phenylglycine ethyl ester with diethyl oxalate followed by reaction with aniline under acid catalysis gave a mixture of diethyl dianilinomaleate and diethyl dianilinofumarate in 54% yield. Upon heating this mixture in a high-boiling inert solvent, 3-anilino-2-ethoxycarbonyl-4-quinolone was obtained in 72% yield. Final ring closure of the quinolone derivative using polyphosphoric acid gave the epindolidione.     

An improved method for 14C-labelling of farnesylacetic acid and its geranyl ester

Farnesylacetic acid was efficiently labelled with 14C at the 5-position and gefarnate, a potent ulcer inhibitor, was prepared from it in radioactive form for use in metabolic studies. Condensation of [carbonyl-14C]acetyl chloride (5) with t-butyl 2-ethoxymagnesiomalonate (6) followed by acid-catalyzed deprotection and decarboxylation gave ethyl 3-oxo[3-14C]butanoate (8). Alkylation of the keto ester (8) with geranyl bromide (9) afforded the unsaturated keto ester (10), which was hydrolyzed and decarboxylated to give geranyl[2-14C]acetone (11). Grignard reaction of 11 with cyclopropylmagnesium bromide followed by treatment with hydrobromic acid yielded [4-14C]homofarnesyl bromide (13). Cyanation of 13 with potassium cyanide and subsequent hydrolysis gave [5-14C]farnesylacetic acid (1) in 6.1% yield from barium [14C]carbonate (3). Chlorination of 1 followed by esterification with geraniol afforded [5-14C]gefarnate (2) in 88% yield.     

Characteristic aroma compounds from different pineapple parts

Characteristic aroma volatile compounds from different parts of cayenne pineapple were analyzed by headspace-solid phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC/MS). The main volatile compounds were esters, terpenes, ketones and aldehydes. The number and content of aroma compounds detected in pulp were higher than those found in core. In pulp, the characteristic aroma compounds were ethyl 2-methylbutanoate, ethyl hexanoate, 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF), decanal, ethyl 3-(methylthio)propionate, ethyl butanoate, and ethyl (E)-3-hexenoate; while in core the main compounds were ethyl 2-methylbutanoate, ethyl hexanoate and DMHF. The highest odor units were found to correspond to ethyl 2-methylbutanoate, followed by ethyl hexanoate and DMHF. The odor units found for pulp were higher than those for core.     

The preparation and aqueous basic oxidation of diethyl 1-methyl-3-hydroxy-5-phenylpyrrole-2,4-dicarboxylate

Diethyl 1-methyl-3-hydroxy-5-phenylpyrrole-2,4-dicarboxylate has been synthesized in good yield from readily available materials, diethyl benzylidenemalonate and ethyl sarcosinate. It was found to react with oxygen in aqueous base to give two oxidation products, ethyl 1-methyl-2-oxo-3-hydroxy-5-phenyl-3-pyrroline-4-carboxylate ( 9 ) and ethyl 1-methyl-2,3-dioxo-5-phenyl-4-pyrroline-4-carboxylate ( 10 ). These two oxidation products are postulated to arise from the decomposition of a common intermediate, diethyl 1-methyl-2-hydroperoxy-3-oxo-5-phenyl-4-pyrroline-2,4-dicarboxylate. Reaction of the title compound with oxygen in pyridine containing Triton B again produced two products, the dioxo compound ( 10 ) and diethyl 1-methyl-2-hydroxy-3-oxo-5-phenyl-4-pyrroline-2,4-dicarboxylate ( 12 ). Compound 12 was shown to react in aqueous base to give exclusively 9 . The hydration of 10 in acidic and basic media is also discussed.     

Fluorocontaining 1,3-Dicarbonyl Compounds in the Synthesis of Pyrimidine Derivatives

Hexafluoroacetylacetone reacts with urea (thiourea) to yield respectively 4,6-bis(hydroxy)-4,6-bis(trifluoromethyl)hexahydropyrimidin-2-one(thione). The dehydration of the products and also reaction of nonsymmetrical fluoroalkyl-containing 1,3-diketones with urea (thiourea) afford substituted pyrimidines. The condensation of fluorinated 3-oxoesters and 1,3-diketones with benzaldehyde and urea (thiourea) results in 5-alkoxycarbonyl(acyl)-4-hydroxy-2-oxo(thioxo)-6-phenyl-4-fluoroalkylhexahydropyrimidines that on dehydration furnish 5-alkoxycarbonyl(acyl)-2-oxo(thioxo)-4-phenyl-6-fluoroalkyltetrahydropyrimidines. Ethyl 7-nonafluorobutyl-5-phenyl-2,3-dihydrothiazolo[3,2-a]pyrimidine-6-carboxylate hydrobromide forms in reaction of dibromoethane with ethyl ether of 2-thioxo-4-phenyl-6-nonafluorobutyltetrahydropyrimidine.     

Application of sec-butanol to the derivatization of hydroxyfuranones.

This paper reports the use of sec-butanol for the derivatization of chlorinated hydroxyfuranones. The following hydroxyfuranones were investigated: 3,4-dichloro-5-hydroxy-2(5H)-furanone, 3,4-dibromo-5-hydroxy-2(5H)-furanone, 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone, and 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone. Their derivatization products were analyzed by gas chromatography/mass spectrometry. The sec-butyl derivatives of the hydroxyfuranones investigated yield ions that are less abundant than those obtained for the corresponding isopropyl derivatives. However, sec-butyl derivatives are easily detectable in especially dirty matrixes because they produce double peaks in the chromatogram. The ion intensity of the first peak in the pair is lower than that of the second peak, but both are characterized by the same spectrum. The formation of multiple peaks is related to the formation of diastereoisomers during derivatization.     

Analysis and some chemical properties of MX (3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone), the potent drinking water mutagen

Summary The solubility of the potent drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in water (50.8, 44.7, 43.7, and 51.0 mg/ml at pH values 2, 5, 7, and 9, respectively) was only slightly dependent on pH, on the contrary to octanol/water partition (log P_ow 1.13, 0.84, –0.44, and –1.02 at pH 2, 5, 7, and 9, respectively). MX was stable in ethyl acetate and acidic water solutions. The recovery of MX during isolation from water or urine samples was about 100% but about 73–82% in the methylation process. The alternative isolation and derivatization methods tested for MX did not give better results.     

Preparative synthesis of ethyl 5-acyl-4-pyrone-2-carboxylates and 6-aryl-, 6-alkyl-, and 5-acylcomanic acids on their basis

A simple and efficient method for the synthesis of ethyl 5-alkanoyl- and 5-aroyl-4-pyrone-2-carboxylates was developed, which is based on the condensation of 1-R-2-(dimethyl-aminomethylidene)butane-1,3-diones, obtained from 1,3-diketones and dimethylformamide dimethyl acetal, with diethyl oxalate in the presence of NaH in THF. Ethyl 5-acyl-4-pyrone-2-carboxylates were used in the synthesis of 6-R- and 5-RCO-comanic acids.