水相中邻苯二醌衍生物的电化学合成与原位转化

以绿色合成为目标的方法和技术是目前有机合成化学研究的重要内容。水相中的有机电化学合成兼有水相有机合成和有机电化学合成两种方法的优点,是一种重要的绿色合成技术,也是目前绿色化学研究的热点之一。研究表明,水相中邻苯二酚电化学氧化生成邻苯醌,该中间体非常活泼,可以与双烯发生[4+2]环加成反应生成烯酮衍生物,或者在亲核试剂的作用下,发生Michael加成反应生成取代邻苯二酚或者苯并杂环衍生物,而这些化合物常常具有各种抗菌、抗病毒(包括HIV)、抗肿瘤、保肝、扩冠等重要的生理作用。因此,水相中邻苯醌的电化学合成及其原位转化是一种有效的合成多羟基芳香化合物及其衍生物的方法。考虑到很多多羟基芳香化合物具有抗HIV整合酶的潜在活性,近三年来,我们开展了多羟基芳香族化合物电化学合成工作。本报告将简单介绍本课题组在这一方面的研究结果。     

3, 5-二叔丁基邻苯二酚的过氧化降解偶合反应研究

3, 5-二叔丁基邻苯二酚过氧化氢氧化制备3, 5-二叔丁基邻苯醌时, 发现在氢氧化钾溶液中发生了氧化降解偶合反应, 制得了3, 5-二叔丁基-5-(2, 4-二叔丁基-6-羟基苯氧基)-2-呋喃酮 2; 并对其生成作了较合理的解释。     

苯酚在碳纳米管修饰玻碳电极表面的电氧化机理研究

以含有苯酚的PBS溶液为电解液,采用循环伏安法研究了苯酚在碳纳米管修饰的玻碳电极表面电化学氧化的机理。结果表明,苯酚在碳纳米管修饰电极表面的氧化机理为：苯酚先于正向扫描中不可逆氧化为苯醌后,在负向扫描中被还原为对苯二酚和邻苯二酚,对苯二酚和邻苯二酚可进一步发生可逆氧化还原反应而存在于溶液中。对苯二酚和邻苯二酚的生成对苯酚氧化形成苯醌的峰电流产生干扰,从而影响苯酚电化学测定的灵敏度和准确性。     

苯酚在多壁碳纳米管修饰的玻碳电极表面的电氧化机理研究

以含有苯酚的PBS溶液为电解液,采用循环伏安法研究了苯酚在碳纳米管修饰的玻碳电极表面电化学氧化的机理。结果表明,苯酚在碳纳米管修饰的电极表面的氧化机理为:苯酚先于正向扫描中不可逆氧化为苯醌后,在负向扫描中被还原为对苯二酚和邻苯二酚,对苯二酚和邻苯二酚可进一步发生可逆氧化还原反应而存在于溶液中。对苯二酚和邻苯二酚的生成对苯酚氧化形成苯醌的峰电流产生干扰,从而影响苯酚电化学测定的灵敏度和准确性。     

2-芳胺基-6-巯基嘌呤衍生物的合成研究

以2,6-二氯嘌呤为原料,分别采用硫脲分步法、硫脲一步法和硫氢化钾法合成2-氯-6-巯基嘌呤(化合物1),比较不同方法的特点以及对产物收率的影响。结果表明,采用硫氢化钾法合成路线,可以使产物收率达到96. 5%,而且产物纯度好,后处理简单。以化合物1为原料,进一步合成了2-氯-6-苄硫基嘌呤(化合物2)以及三种2-芳胺基-6-巯基嘌呤衍生物(3a～3c),并研究了微波辐射对2-[(4-苄氧基)苯胺基]-6-巯基嘌呤(3c)合成反应的影响,结果表明,微波辐射可以有效提高反应速率,缩短反应时间,产率提高到66. 3%。产物结构经1H NMR表征。     

4 ,5-二取代-1 ,2-苯醌的电化学合成及反应机制

邻苯二酚在不同亲核试剂存在下经电解氧化 ,一步合成了 4,5_二取代_1,2_苯醌类化合物 ;对电解氧化_迈克尔加成反应进行了探讨 ,提出了可能的反应历程 .     

Sc(Ⅲ)催化胺对邻亚甲基苯醌氮杂迈克尔加成反应合成贝蒂碱衍生物

邻亚甲基苯醌化合物是一类非常活泼和重要的中间体,被广泛应用于天然产物和药物化学中.以2-[羟基(苯基)甲基]苯酚类化合物和胺为原料,1,2-二氯乙烷为溶剂,在Sc(III)促进下原位生成邻亚甲基苯醌,并发生氮杂迈克尔加成反应合成贝蒂碱衍生物.反应在封管条件下90℃搅拌4 h完成,以76%～96%的产率得到目标产物.     

单壁碳纳米管-氧化石墨烯复合修饰电极测定邻苯二酚

制备了用于测定邻苯二酚的单壁碳纳米管-氧化石墨烯复合修饰玻碳电极.用循环伏安法研究了邻苯二酚在该电极上的电化学行为.结果表明,该修饰电极对邻苯二酚具有良好的电催化性能.在最佳实验条件下,采用差分脉冲伏安法对邻苯二酚进行了测定,其氧化峰电流与邻苯二酚浓度在2×10~(-6)~1×10~(-4) mol/L范围内呈线性关系,相关系数为0.996 2,检出限为4×10~(-7) mol/L.该电极具有良好的重现性,用于模拟废水中邻苯二酚的测定结果令人满意.     

重氮化反应高效合成1H-吲唑-3-羧酸衍生物

报道了邻氨基苯乙酰胺和邻氨基苯乙酸酯在重氮化试剂作用下直接转化为对应的1H-吲唑-3-羧酸衍生物.该反应操作简单,反应条件温和,反应迅速,产率高,底物范围广,为1H-吲唑-3-羧酸衍生物的合成提供了一种更加高效简洁的新方法.该方法被成功应用于药物分子格拉司琼和氯尼达明的合成,分别以46%和60%的总收率得到了目标产物.初步的机理研究表明重氮盐是该反应的关键中间体.     

2,4-二氯苯酚的电化学氧化降解反应研究

采用循环伏安法和原位红外光谱技术研究了2,4-二氯苯酚在Pt电极上的电化学氧化降解反应,结合Fukui函数值预测了2,4-二氯苯酚在电化学氧化过程中的反应位点. 结果表明,Pt电极对2,4-二氯苯酚有良好的电催化活性,2,4-二氯苯酚在电极表面反应主要有3个途径：直接通过电化学反应脱去氯离子,生成苯酚;在·OH的进攻下,C—Cl键断裂,4位Cl较2位Cl先脱去,生成苯二酚,并可进一步氧化生成苯醌以及不饱和羧酸;在·OH的进攻下发生苯环开环反应,生成含氯不饱和羧酸. 在1700 mV左右,2,4-二氯苯酚可经电化学氧化生成CO₂.     

Study of the oxidation of some catechols in the presence of 4‐amino‐3‐thio‐1,2,4‐triazole by digital simulation of cyclic voltammograms

Electrochemical oxidation of catechol and its derivatives ( 1a–d ) has been studied in the presence of 4‐amino‐3‐thio‐1,2,4‐triazole ( 3 ) at various pHs. Some electrochemical techniques such as cyclic voltammetry using the diagnostic criteria derived by Nicholson and Shain for various electrode mechanisms and controlled‐potential coulometry were used. Results indicate the participation of catechols ( 1a–d ) with 3 in an intramolecular cyclization reaction to form the corresponding 1,2,4‐triazino[5,4‐b]‐1,3,4‐thiadiazine derivatives. In various scan rates, based on an electron transfer–chemical reaction–electron transfer–chemical reaction mechanism, the observed homogeneous rate constants (k_obs) for Michael addition reaction were estimated by comparing the experimental cyclic voltammetric responses with the digital simulated results. The oxidation reaction mechanism of catechols ( 1a–d ) in the presence of 4‐amino‐3‐thio‐1,2,4‐triazole ( 3 ) was also studied. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 340–345, 2007     

Protecting‐Group‐Free Total Synthesis of Isoquinoline Alkaloids by Nickel‐Catalyzed Annulation of o‐Halobenzaldimine with an Alkyne as the Key Step

An efficient short total synthesis of benzo[c]phenanthridine alkaloids including oxyavicine, oxynitidine, and oxysanguinarine is described. Thus, N‐methyl‐o‐bromobenzaldimines 1 b – d undergo regioselective cyclization with 4‐(benzo[d][1,3]dioxol‐5‐yl)but‐3‐yn‐1‐ol ( 2 b ) in the presence of [Ni(cod)₂] (cod=1,5‐cyclooctadiene). In situ oxidation of the resultant isoquinolinium salts gives isoquinolinone derivatives 5 b – d with benzo[d][1,3]dioxol‐5‐yl substitution at the C₃ atom and a (CH₂)₂OH group at the C₄ atom. Later, oxidation of the alcohol group in 5 b – d to the aldehyde moiety followed by acid‐catalyzed cyclization and dehydration completes the total syntheses to give oxyavicine, oxynitidine, and oxysanguinarine in 67, 65, and 60 % yields, respectively. The synthesis requires four steps from o‐bromobenzaldehyde derivatives. Transformations of these alkaloids to the other alkaloids in this family are also discussed herein.     

Electrochemical oxidation of catechols in the presence of ethyl‐2‐chloroacetoacetate. Synthesis and mechanistic study

Electrochemical oxidation of catechol and some of 3‐substituted catechols ( 1a‐c ) has been studied in the presence of ethyl‐2‐chloroacetoacetate ( 3 ) in water/acetonitrile (90:10) solution using cyclic voltammetry and controlled‐potential coulometry. The results indicate that the quinones derived from catechols ( 1a‐c ) participate in Michael addition reactions with ethyl‐2‐chloroacetoacetate( 3 ), with consumption of only two electrons per molecule of 1 , to form the corresponding benzofurans ( 10a‐c ). The electrochemical synthesis of benzofurans ( 10a‐c ) has been successfully performed at a carbon rod electrode and in an undivided cell with good yields and purity. A new two‐electron mechanism for the electrode process is proposed.     

Electro‐Oxidation of 3,4‐Dihydroxybenzoic Acid in the Presence of 6‐Methyl‐1,2,4‐Triazine‐3‐Thione‐5‐One: Unique Synthesis of 7H‐Thiazolo[3,2‐b]‐1,2,4‐Triazin‐7‐One Derivative in Aqueous Media

The electrochemical oxidation of 3,4‐dihydroxy benzoic acid ( 1 ) has been studied in the presence of 6‐methyl‐1,2,4‐triazine‐3‐thione‐5‐one ( 2 ) in aqueous solution. The oxidation mechanism of 1 and its reaction in the presence of 2 was offered. It was confirmed that 1 is converted to 7H‐thiazolo[3,2‐b]‐1,2,4‐triazin‐7‐one derivative 5 through Michael addition reaction of 2 to anodically generated o‐benzoquinone. The results of the research were used for electrochemical synthesis of 5 in an undivided cell in good yield and purity.     

O-氯丙基和O-氰丙基间苯二酚杯芳烃的合成，晶体结构和电化学性质

四烃基和四二茂铁基间苯二酚杯芳烃在丙酮回流条件和碳酸钾存在下用1-溴-3-氯丙烷或4-氯丁腈进行烃基化反应分别生成全取代的O-氯丙基和O-氰丙基间苯二酚杯芳烃,晶体结构测定表明烷基间苯二酚杯芳烃倾向于以全顺式构型存在,而芳基间苯二酚杯芳烃倾向于以顺-反-反式构型存在。本文还已经了四二茂铁基间苯二酚杯芳烃的电化学性质。     

A New Route to Vitamin E Key‐Intermediates by Olefin Cross‐Metathesis

Ru‐Catalyzed olefin cross‐metathesis (CM) has been successfully applied to the synthesis of several phytyl derivatives ( 2b, 2d – f, 3b ) with a trisubstituted C?C bond, as useful intermediates for an alternative route to α‐tocopheryl acetate (vitamin E acetate; 1b ) (Scheme 1). Using the second‐generation Grubbs catalyst RuCl₂(C₂₁H₂₆N₂)(CHPh)PCy₃ (Cy = cyclohexyl; 4a ) and Hoveyda–Grubbs catalyst RuCl₂(C₂₁H₂₆N₂){CH‐C₆H₄(O‐ⁱPr)‐2} ( 4b ), the reactions were performed with various C‐allyl ( 5a – f, 7a,b ) and O‐allyl ( 8a – d ) derivatives of trimethylhydroquinone‐1‐acetate as substrates. 2,6,10,14‐Tetramethylpentadec‐1‐ene ( 6a ) and derivatives 6c – e of phytol ( 6b ) as well as phytal ( 6f ) were employed as olefin partners for the CM reactions (Schemes 2 and 5). The vitamin E precursors could be prepared in up to 83% isolated yield as (E/Z)‐mixtures.     

Influence of Halogen Substitution in the Ligand Sphere on the Antitumor and Antibacterial Activity of Half‐sandwich Ruthenium(II) Complexes [RuX(η6‐arene)(C5H4N‐2‐CH=N‐Ar)]+

New complexes [(η⁶‐p‐cymene)Ru(C₅H₄N‐2‐CH=N–Ar)X]PF₆ [X = Br ( 1 ), I ( 2 ); Ar = 4‐fluorophenyl ( a ), 4‐chlorophenyl ( b ), 4‐bromophenyl ( c ), 4‐iodophenyl ( d ), 2,5‐dichlorophenyl ( e )] were prepared, as well as 3a – 3e (X = Cl) and the new complexes [(η⁶‐arene)RuCl(N‐N)]PF₆ (arene = C₆H₅OCH₂CH₂OH, N‐N = 2,2′‐bipyridine ( 4 ), 2,6‐(dimethylphenyl)‐pyridin‐2‐yl‐methylene amine ( 5 ), 2,6‐(diisopropylphenyl)‐pyridin‐2‐yl‐methylene amine ( 6 ); arene = p‐cymene, N‐N = 4‐(aminophenyl)‐pyridin‐2‐yl‐methylene amine ( 7 )]. X‐ray diffraction studies were performed for 1a , 1b , 1c , 1d , 2b , 5 , and 7 . Cytotoxicities of 1a – 1d and 2 were established versus human cancer cells epithelial colorectal adenocarcinoma (Caco‐2) (IC₅₀: 35.8–631.0 μM), breast adenocarcinoma (MCF7) (IC₅₀: 36.3–128.8.0 μM), and hepatocellular carcinoma (HepG2) (IC₅₀: 60.6–439.8 μM), 3a – 3e were tested against HepG2 and Caco‐2, and 4 – 7 were tested against Caco‐2. 1 – 7 were tested against non‐cancerous human epithelial kidney cells. 1 and 2 were more selective towards tumor cells than the anticancer drug 5‐fluorouracil (5‐FU), but 3a – 3e (X = Cl) were not selective. 1 and 2 had good activity against MCF7, some with lower IC₅₀ than 5‐FU. Complexes with X = Br or I had moderate activity against Caco‐2 and HepG2, but those with Cl were inactive. Antibacterial activities of 1a , 2b , 3a , and 7 were tested against antibacterial susceptible and resistant Gram‐negative and ‐positive bacteria. 1a , 2b , and 3a showed activity against methicillin‐resistant S. aureus (MIC = 31–2000 μg · mL^–1).     

A Facile and Efficient One‐Pot Electrochemical Synthesis of Thiazole Derivatives in Aqueous Solution

In the present work, the electrooxidation of hydroquinones 1a and 1b , and catechols 1c and 1d was studied in the presence of rhodanine ( 3 ) as nucleophile in a mixture of EtOH and phosphate buffer solution as ‘green’ media using cyclic voltammetry and controlled‐potential coulometry. The results indicated that the corresponding p‐ and o‐quinones formed from the hydroquinones and catechols, respectively, participate in Michael addition reaction to yield new thiazole derivatives. The electrochemical syntheses of these new thiazole derivatives were performed successfully at three graphite rod electrodes in undivided cells in good‐to‐excellent yields at room temperature without any catalyst.     

Redox Non‐Innocence and Isomer‐Specific Oxidative Functionalization of Ruthenium‐Coordinated β‐Ketoiminate

This article deals with isomeric ruthenium complexes [Ru^III(L^R)₂(acac)] (S=1/2) involving unsymmetric β‐ketoiminates (AcNac) (L^R=R‐AcNac, R=H ( 1 ), Cl ( 2 ), OMe ( 3 ); acac=acetylacetonate) [R=para‐substituents (H, Cl, OMe) of N‐bearing aryl group]. The isomeric identities of the complexes, cct (cis‐cis‐trans, blue, a ), ctc (cis‐trans‐cis, green, b ) and ccc (cis‐cis‐cis_, pink, c ) with respect to oxygen (acac), oxygen (L) and nitrogen (L) donors, respectively, were authenticated by their single‐crystal X‐ray structures and spectroscopic/electrochemical features. One‐electron reversible oxidation and reduction processes of 1 – 3 led to the electronic formulations of [Ru^III(L)(L ^? )(acac)]⁺ and [Ru^II(L)₂(acac)]^? for 1 ⁺‐ 3 ⁺ (S=1) and 1^? – 3^? (S=0), respectively. The triplet state of 1 ⁺‐ 3 ⁺ was corroborated by its forbidden weak half‐field signal near g≈4.0 at 4 K, revealing the non‐innocent feature of L. Interestingly, among the three isomeric forms ( a – c in 1 – 3 ), the ctc ( b in 2 b or 3 b ) isomer selectively underwent oxidative functionalization at the central β‐carbon (C?H→C=O) of one of the L ligands in air, leading to the formation of diamagnetic [Ru^II(L)(L ′ )(acac)] (L ′ =diketoimine) in 4 / 4′ . Mechanistic aspects of the oxygenation process of AcNac in 2 b were also explored via kinetic and theoretical studies.     

Migratory Shift in Oxidative Cyclodehydrogenation Reaction of Tetraphenylethylenes Containing Electron‐Rich THDTAP Moiety

Four tetraphenylethylenes ( 2 a – d ) containing an electron‐rich 2,3,4,6‐tetrahydro‐1,6‐dithia‐3a‐azaphenalene (THDTAP) moiety have been synthesized. The 2 a – d show aggregation‐induced emission (AIE) with yellowish green photoluminescence (PL) in THF‐H₂O (v/v, 1:9) solution and in the solid state. Compounds 2 a – d undergo 1,2‐migratory shift in oxidative cyclodehydrogenation reactions to afford the unexpected products 3 a – d which display green PL in CH₂Cl₂ solution and are non‐emissive in the solid state. The PL intensities of 3 a – d are clearly enhanced in the presence of meta‐chloroperoxybenzoic acid (mCPBA) owing to the oxidation of the S‐atoms on the THDTAP moiety. In contrast, the PL of 2 a – d in THF‐H₂O (v/v, 1:9) solution is quenched by adding mCPBA, ascribable to the oxidation of the C=C bond on the ethylene moiety. It is found that the absorption of 3 a – d is distinctly red‐shifted from the UV/Vis region to the NIR region upon acidification, arising from the protonation of the N‐atom on the THDTAP moiety. Furthermore, 3 a – d display nonlinear optical response (NLO) and optical limiting (OL) behaviour which is superior to that of the well‐known OL material C₆₀.