2(5H)-呋喃酮与含氮亲核试剂反应研究进展

2(5H)-呋喃酮作为一种α,β-不饱和环丁内酯,可发生多种反应,特别是其不饱和碳碳双键上连有卤素时,2(5H)-呋喃酮的高反应性使其被广泛应用于有机合成.按照反应后五元环内酯产物上取代基位置的不同,综述了2(5H)-呋喃酮与含氮亲核试剂通过Michael加成、串联的Michael加成-消除、偶极环加成和钯催化耦合等反应合成β-取代、α,β-取代和γ-取代环状衍生物在近十几年的研究进展.     

(5S)-5-烷氧基-3,4-二卤-2(5H)-呋喃酮与氨基酸的串联反应

在氢氧化钾作用下,直接以不同种类氨基酸为亲核试剂,与手性(5S)-5-烷氧基-3,4-二卤-2(5H)-呋喃酮在室温下进行串联的不对称迈克尔加成-消除反应,合成了15个新的光学活性2(5H)-呋喃酮衍生物.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,确定了目标化合物的化学结构和绝对构型.     

5-芳酰氨基-2-苯基-2H-1, 2, 4-噻二唑-3-酮的合成

用1-芳酰基-5-苯基-2-硫代双脲与溴进行氧化成环反应制备了九个新的5-芳酰氨基-2-苯基-2H-1, 2, 4-噻二唑-3-酮, 相应的1-芳酰基-5-苯基-2-硫代双脲可以通过苯基脲与酰基异硫氰酸酯加成制得。     

(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。     

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.     

一锅法合成4-(5-芳基-1,3,4-噻二唑-2-氨甲基)苯酚衍生物

以2-氨基-5-芳基噻二唑衍生物和对羟基苯甲醛为原料,经亲核加成/脱水、还原两步一锅法合成了一系列新的4-(5-芳基-1,3,4-噻二唑-2-氨甲基)苯酚衍生物,反应具有时间短、后处理简单等优点.采用元素分析,NMR,IR以及质谱等多种谱学技术对产物进行了详细表征.     

4-(5-喹啉-3-基-四氮唑-2-基)丁胺的合成

三苯基膦钯催化3-溴喹啉完成氰化取代制得3-氰喹啉(1);1与叠氮化钠经[2+3]环加成合成了3-(2H-四氮唑-5-基)喹啉(2);2与N-(4-溴丁基)邻苯二甲酰亚胺反应制得2-[4-(5-喹啉-3-基-四氮唑-2-基)丁基]异吲哚-1,3-二酮(3);3经肼解合成了4-(5-喹啉-3-基-四氮唑-2-基)丁胺(4...     

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。     

5-烷氧基-4-环胺基-3-卤-2(5H)-呋喃酮的合成与表征

在氟化钾作用下,亲核试剂环状仲胺与5-烷氧基-3,4二卤-2(5H)-呋喃酮在室温下发生串联的迈克尔加成-消除反应,合成了17个新化合物.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,确定了目标化合物的化学结构和绝对构型.     

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Ft抖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（1HNMR）、核磁共振碳谱（13CNMR）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。     

5-Hydroxy-3-phenyl-5-vinyl-2-isoxazoline and 3-phenyl-5-vinylisoxazole: synthesis and reactivity

5-Hydroxy-3-phenyl-5-vinyl-2-isoxazoline has been synthesized by reacting benzonitrile oxide with the enolate ion of methyl vinyl ketone. From 5-hydroxy-5-vinyl-2-isoxazoline, 5-vinylisoxazole was then quantitatively obtained by dehydration-aromatization under acidic conditions. Similar results, though not quantitative, were also found by treatment in 2-propanol under basic conditions (i-PrOH/H₂O, Na₂CO₃, reflux). In contrast to 2-propanol, reactions performed in methanol (and, in part, those carried out in ethanol) revealed a more complex behaviour, the nucleophilic addition of ROH onto the vinyl group being mainly observed. Nucleophilic addition was also found with alkyllithiums. The mechanism of the nucleophilic addition is discussed. Epoxidation and further reaction with benzonitrile oxide of both 3-hydroxy-5-phenyl-5-vinyl-2-isoxazoline and 3-phenyl-5-vinylisoxazole are also described.     

Stereoselective synthesis of the 5'-hydroxy-5'-phosphonate derivatives of cytidine and cytosine arabinoside

Both the (R)- and (S)-5'-hydroxy 5'-phosphonate derivatives of cytidine and cytosine arabinoside (ara-C) have been prepared via phosphite addition or a Lewis acid mediated hydrophosphonylation of appropriately protected 5'-nucleoside aldehydes. Phosphite addition to a cytosine aldehyde protected as the 2',3'-acetonide gave predominately the 5'R isomer, while phosphite addition to the corresponding 2',3'-bis TBS derivative favored the 5'S stereochemistry. In contrast, phosphite addition to the 2',3'-bis TBS protected aldehyde derived from ara-C gave only the 5'R adduct. However, TiCl(4)-mediated hydrophosphonylation of the same ara-C aldehyde favored the 5'S stereoisomer by a 2:1 ratio. Once all four of the diastereomers were in hand, the stereochemistry of these compounds could be assigned based on their spectral data or that obtained from their O-methyl mandelate derivatives. After hydrolysis of the phosphonate esters and various protecting groups, the four alpha-hydroxy phosphonic acids were tested for their ability to serve as substrates for the enzyme nucleoside monophosphate kinase and for their toxicity to K562 cells.     

Reaction of allenylmagnesium and allenylindium bromides with nitrile oxides: synthesis of novel 5-butynyl- and 5-methylisoxazoles

5-Butynylisoxazoles were obtained in high yields through a domino addition, C-O heterocyclization involving allenylmagnesium bromide and benzonitrile oxide in dry THF, in which the corresponding 5-methylisoxazoles were isolated in trace amounts. However, when the reactions were attempted in aqueous media using allenylindium bromide, 5-methylisoxazoles were formed as the sole products in high yields.     

Synthesis of 5-methyl-5-octyloxycarbonylnorborn-2-yl (meth)acrylates

[4+2]-Cycloaddition of cyclopentadiene to octyl methacrylate with dicyclopentadiene used as starting compound, and also thermal and catalytic addition of (meth)acrylic acids to 5-methyl-5-octyloxycarbonylnorborn-2-ene in the presence of a catalyst, BF₃O(C₂H₅)₂, were studied. 5-Methyl-5-octyloxycarbonylnorborn-2-yl (meth) acrylates, new monomers for polymer synthesis, were prepared.     

5-氟尿嘧啶和5-氯尿嘧啶及其互变异构体的理论计算研究

采用HF/3-21G方法, 对6种气相和水相中可能存在的5-氟尿嘧啶(和5-氯尿嘧啶)互变异构体进行了构象分析.采用B3LYP/6-311＋G**方法对处于优势构象时的各互变异构体进行了几何全优化, 并计算出它们的总能量、焓、熵、吉布斯自由能. Onsager反应场溶剂模型用于水相的计算. 计算结果表明, 5-氟尿嘧啶和5-氯尿嘧啶在气相中和水相中主要以双酮形式存在. 5-氟尿嘧啶和5-氯尿嘧啶的熵效应小, 对互变异构平衡没有显著的影响, 而焓变对互变异构产生了主要的影响. 讨论了水溶剂化作用对异构体的能量、电荷分布和偶极矩的影响. 溶剂化自由能与异构体的气相偶极矩存在相关性. 另外, 详细地将5-氟尿嘧啶和5-氯尿嘧啶与尿嘧啶进行了对比, 获得三者最稳定异构体间电子结构异同的有用信息.     

Synthesis of polyamideamines from 5-oxazolones

Polyamideamines with a sequence of two amide and one amine linkage in a main chain were synthesized from the polyaddition of 2-isopropylidene-4-alkyl-3-oxazolin-5-ones and primary diamines. The polyaddition reaction proceeded through 1,4-conjugate addition of an amine group to 3-oxazolin-5-one and subsequent ring opening of the intermediate addition product with another amine. Although aliphatic diamines gave oily polymers, xylylenediamines afforded amorphous solid polymers. The reduced viscosities and polymer melt temperature of the polymers were 0.05–0.12 and 90–130°C., respectively.     

Ring transformations of aziridinyl 2-phosphonates: synthesis of 5-phosphono-2-oxazolidinones and 5-phosphono-2-imidazolidinones

Syntheses of 5-phosphono-2-oxazolidinones and 5-phosphono-2-imidazolidinones were achieved from the corresponding 1-vinyl-2-phosphonoaziridines. Regioselective aziridine ring opening employing methyl chloroformate affords 1-amido-2-chloroethylphosphonates, which were easily transformed into the corresponding 2-oxazolidinones upon heating in dimethyl sulfoxide. Treatment of the aziridine ring opening products with ammonia furnishes vinylphosphonates, which undergo a Michael type addition with several amines. In situ ring closure of the addition products yields the corresponding phosphonylated 2-imidazolidinones.     

On the synthesis and animation of 5-chloro-and 5-bromo-1,7-naphthyridine

A new synthesis of 5-chloro- and 5-bromo-1,7-naphthyridine, using 8-amino-1,7-naphthyridine as starting material is described. On amination with potassium amide in liquid ammonia, the 5-bromo compound undergoes a tele-amination into 8-amino- and 2-amino-1,7-naphthyridine and a Chichibabin reaction yielding 8-amino-5-bromo-1,7-naphthyridine. The reaction with the 5-chloro compound occurs at a much lower rate than the 5-bromo compound and only gives 8-amino-5-chloro-1,7-naphthyridine in a small yield. Convincing ¹H-nmr evidence is presented, showing that the 5-bromo- and 5-chloro-1,7-naphthyridine give addition of the amide ion at position 8 and that the 5-chloro compound also gives addition at position 2.     

Synthesis of 2-Amino-5-hydroxy-5-phosphonovaleric Acid

Russian Journal of General Chemistry - The synthesis of a new analog of 2-amino-5-phosphonovaleric acid (AP5), namely 2-amino-5-hydroxy-5-phosphonovaleric acid, by successive Michael addition of...     

Total synthesis of nor-1,6-germacradien-5-ols

The first total synthesis of (+/-)-nor-1,6-germacradien-5-ols is described. The synthetic route involves the RCM methodology for the ring formation and a selective 1,2 addition of MeLi to cyclodecenone. By altering the order of the last synthetic steps, TBSO-protected (+/-)-(1Z,6E)-nor-1,6-germacradien-5-ols (+/-)-(5S*,8R*)-16 and -(+/-)-(5S*,8S*)-16 were obtained. The synthetic strategy via cyclodecenone offers the possibility of preparing different analogues of the title compounds through addition of other nucleophiles. Moreover, nor-germacrene D could be accessed from the target molecule by methylenation of its carbonyl moiety. (+/-)-nor-1,6-Germacradien-5-ol [(+/-)-(1E,5S*,6E,8S*)-2] was synthesized in eight steps from isovaleric acid. The 10-membered ring was formed by RCM, and the tertiary alcohol moiety was introduced in the last step via a highly diastereoselective addition of MeLi to (+/-)-(1E,6E)-1,6-cyclodecen-5-one (+/-)-E,E-5. Addition of MeLi to cyclodecenone (+/-)-Z,E-5 also occurred with complete selectivity to provide (+/-)-(1Z,5S*,6E,8S*)-2. A slightly different synthetic pathway was also explored, in which the order of the final synthetic steps was switched: the enone formation and the addition of MeLi were conducted prior to the cyclization. When the hydroxy group was protected as a TBS ether, the newly formed olefin had exclusively Z configuration. Thus, TBSO-protected (+/-)-(1Z,6E)-nor-1,6-germacradien-5-ols (+/-)-16 were obtained as a 1:1 (5S*,8S*)/(5R*,8S*) mixture. The NMR spectra of these two diastereomers confirmed the relative stereochemistry of natural (-)-1,6-germacradien-5-ol (1) at C5 and C8.