乙酰基香豆素及其衍生物与吲哚的固相光反应研究

乙酰基香豆素及其衍生物与吲哚的固相光反应研究杜大明，王永梅，孟继本，周秀中张慧萍（南开大学化学系，天津，３０００７１）（云南师范大学化学系）关键词香豆素，吲哚，固相光反应近年来固相光化学发展非常迅速，引起国内外学者的关注［１～３］．我们研究了异种分子...     

合成双吲哚甲烷类衍生物的研究进展

双吲哚甲烷类衍生物具有丰富的生物活性和药理活性,在医药领域得到了广泛的应用.近年来,对双吲哚甲烷类衍生物的合成研究引起了人们的热点关注.对双吲哚甲烷类衍生物的合成方法进行了综述,并将催化剂按照不同的类型分为:(1)路易斯酸催化剂,(2)分子碘催化剂,(3)质子酸催化剂,(4)固载催化剂,(5)杂多酸催化剂,(6)有机小分子催化剂,(7)配合物催化剂,(8)离子液体催化剂,(9)其它类型的催化剂.     

微波促进下三组分反应构建3-取代吲哚衍生物

吲哚化学的研究是杂环化学中最活跃的领域之一,特别是有关3-取代吲哚衍生物的合成.3-取代吲哚衍生物可以构建许多天然产物和相应具有生物活性化合物,其合成方法的研究格外令人关注.介绍了在微波辐射下,通过取代苯甲酰甲醛水合物、取代苯胺和4-羟基香豆素三组分,在三氟乙酸的催化下反应构建一系列官能团化的3-取代吲哚衍生物.该反应具有反应操作简单、原料廉价易得及原子经济性高等优点.     

3-吲哚羧酸酯类化合物合成方法的研究进展

吲哚衍生物因其可以亲和多种受体而被认为是设计药物先导化合物的优势结构.其中,3-吲哚羧酸酯类化合物是广泛存在于天然产物及药物分子中的重要的结构单元,如盐酸阿比多尔、托烷司琼、PD 0298029、Grandilodine A等均为3-吲哚羧酸酯类药物分子或天然产物.基于此,近年来关于3-吲哚羧酸酯类化合物及其衍生物的合成不断地被报道,金属催化的以及非金属条件下的合环反应用来构建吲哚中的吡咯环是近年来研究的热点,而在吲哚C-3位直接进行官能团化合成酯基官能团同样具有较高的效率.在相关研究的基础上,按照上述分类方法,综述了近年来3-吲哚羧酸酯类化合物的合成研究进展.     

疏水作用对光化学和光物理过程的影响——Ⅷ.N-烷基吲哚在不良溶剂中的簇集及其荧光光谱

本文研究了链长不同的N-烷基吲哚和3-甲基-N-烷基吲哚在二甲基亚砜-水(DMSO-H_2O)混合溶剂中的稳态和时间分辩荧光光谱,发现随混合溶剂中水的体积分数增大、短链吲哚衍生物的荧光峰位置红移。荧光寿命增长、而长链吲哚衍生物荧光峰位置明显兰移、荧光寿命变短。表明长链吲哚衍生物在混合溶剂中发生簇集,簇集体中微环境的极性和环己烷相似,利用时间分辨荧光光谱计算出长链吲哚衍生物在溶液本体相和簇集体中的分布。     

疏水作用对光化学和光物理过程的影响——Ⅷ.N-烷基吲哚在不良溶剂中的簇集及其荧光光谱

本文研究了链长不同的N-烷基吲哚和3-甲基-N-烷基吲哚在二甲基亚砜-水(DMSO-H_2O)混合溶剂中的稳态和时间分辩荧光光谱, 发现随混合溶剂中水的体积分数增大、短链吲哚衍生物的荧光峰位置红移。荧光寿命增长、而长链吲哚衍生物荧光峰位置明显兰移、荧光寿命变短。表明长链吲哚衍生物在混合溶剂中发生簇集,簇集体中微环境的极性和环己烷相似, 利用时间分辨荧光光谱计算出长链吲哚衍生物在溶液本体相和簇集体中的分布。     

核苷研究Ⅴ: 双乙酰赛吲哚毒素的全合成

赛吲哚霉素的双乙酰衍生物已由吲哚曼 -吲哚法合成。吲哚-3-乙酸经催化氢化, 甲酯化和氨解反应得到吲哚曼-3-乙酰胺(9); 将4-去氧-D-核-吡喃己糖以三苯甲基保护后乙酰化。消除保护基再经氧化和甲酯化等反应, 得到1,2,3-O-三乙酰基-4-去氧-β-D-核-吡喃己糖醛酸甲酯(6), 将化合物6和9先缩合后脱氢即得到赛吲哚霉素的双乙酰衍生物2。赛吲哚霉素的类似物1-(3-氨羰甲基吲哚基)-2,3,4,6-O-四乙酰基-β-D-吡喃葡萄糖苷(13)也由相似的方法合成。     

核苷研究——Ⅴ.双乙酰赛吲哚霉素的全合成

赛吲哚霉素的双乙酰衍生物已由吲哚瞒-吲哚法合成.吲哚-3-乙酸经催化氢化,甲酯化和氨解反应得到吲哚瞒-3-乙酰胺(9);将4-去氧-D-核-吡喃己糖以三苯甲基保护后乙酰化.消除保护基再经氧化和甲酯化等反应,得到1,2,3-O-三乙酰基-4-去氧-β-D-核-吡喃己糖醛酸甲酯(6),将化合物6和9先缩合后脱氢即得到赛吲哚霉素的双乙酰衍生物2.赛吲哚霉素的类似物1-(3-氨羰甲基吲哚基)-2,3,4,6-O-四乙酰基-β-D-吡喃葡萄糖苷(13)也由相似的方法合成.     

新型苯并咪唑取代的丙烯腈及丙烯酸酯衍生物的催化合成

从邻苯二胺出发,合成了2-氰甲基苯并咪唑,在优选出的催化剂吗啡啉/乙酸催化下,合成了新型的双苯并咪唑丙烯腈衍生物和3-吲哚-2-苯并咪唑丙烯腈衍生物;将2-氰甲基苯并咪唑经过碱性水解、酯化,得到苯并咪唑乙酸乙酯,后者经过Knoevenagel缩合/分子内酯交换接续反应高产率地得到了新型的苯并咪唑取代的香豆素衍生物。     

新型双吲哚马来酰亚胺衍生物的合成

以1-(3-氧代四氢吡喃丙基)-吲哚-3-乙醛酸甲酯(5)和吲哚-3-乙酰胺(6)为原料,在催化剂叔丁醇钾的四氢呋喃溶液存在下发生偶合反应,经浓盐酸处理得脱保护的中间体7,再经甲磺酰化反应、氨解反应得到4种新的具有不同氨烷基侧链的双吲哚马来酰亚胺衍生物9a,9b,9d,9e.目标产物结构通过1H NMR,13C NMR,MS和HRMS确证.     

含氮杂环化合物的固相光化学

本文研究了含氮杂环化合物同尿嘧啶醛、芳香醛酮、稠环化合物的固相光化学反应, 得到与液相光化学反应不同的结果。合成了十九种新化合物, 它们的结构由IR, ^1H NMR, MS和元素分析确定。用光谱方法表征了混晶的性质。X射线粉未衍射和差热分析表明, 吲哚同萘, 咔唑同蒽的混晶, 形成了分子化合物。对反应机理进行了初步探讨。     

Solid state reactions of nitrogenous heterocyclic compounds (II)

Solid state Michael addition reaction of indole with α, β-unsaturated carbonyl compounds was carried out, by which a series of compounds containing three different heterocyclic groups binding to one carbon atom were ob-tained. In the presence of Lewis acid, indole could undergo the solid state condensation reaction with aromatic ketones and aldehydes or quinones. The solid state reaction showed higher selectivity and yield than solution reaction. The structures of products were identified by IR,¹H NMR, MS. elemental analysis and X-ray crystal analysis. The reac-tion mechanism was also proposed. Project supported by the National Natural Science Foundation of China     

SOLID-STATE PHOTOCHEMISTRY OF INDOLES WITH NAPTHALENE AND PHENANTHRENE

Abstract— Solid-state irradiation of mixed crystals prepared by meltinga 1:3 molar mixture of indole and phenanthrene followed by resolidifying the melt gave an adduct 2a in 13.5% yield. An adduct 2b was obtained by irradiation of the mixed crystals of 3-methylindole and phenanthrene. Irradiation of the same mixtures of indoles and phenanthrene in solution gave no photoproduct. Irradiation of the mixed crystals of indole and naphthalene gave a similar photoadduct 3a, which was also formed in solution. The 1:1 mixed crystals of indole and phenanthrene and of indole and naphthalene were characterized by various spectroscopic methods. Among them powder X-ray diffraction spectral analysis and differential scanning calorimetry revealed that the former mixed crystal is a simple mixture of microcrystals of indole and phenanthrene, while the latter forms a molecular compound.     

Solid state reaction of aromatic ketones with heteroaromatics

The solid state reactions of p-nitroacetophenone,acetyl-ferrocene with indole were catalyzed by anhydrous zinc chloride or aluminum chloride,and gave exclusively the 1:2 condensation products.The solid state condensation of aromatic ketones with l-phenyl-3-methyl-5-pyrazolone was also investigated,and the 1:1 and 2:1 condensation products were obtained.The structures of eleven new products were determined by IR,MS,1H NMR and elemental analysis.     

Mechanochemical preparation of hydrogen-bonded adducts between the diamine 1,4-diazabicyclo[2.2.2]octane and dicarboxylic acids of variable chain length: an X-ray diffraction and solid-state NMR study

Mechanical mixing of solid dicarboxylic acids of variable chain length HOOC(CH(2))(n)COOH (n = 1-7) with solid 1,4-diazabicyclo[2.2.2]octane generates the corresponding salts or co-crystals of the formula [N(CH(2)CH(2))(3)N]-H-[OOC(CH(2))(n)COOH] (n=1-7). Preparation of the same systems from solution has been instrumental for a full characterization of the mechanochemical products by means of single-crystal and powder-diffraction X-ray analyses, as well as by solid-state NMR. The acid-base adducts, whether involving proton transfer from the COOH group to the N-acceptor, that is having ((-))O...H-N((+)) interactions, or the formation of neutral O-H...N hydrogen bonds, show a melting point alternation phenomenon analogous to that shown by the neutral carboxylic acids. The carbon chemical shift tensors of the COOH group obtained from the sideband intensity of low speed spinning NMR spectra provide a reliable criterion for assigning the protonation state of the adducts.     

固相萃取-高效液相色谱法同时测定羊肉制品中9种杂环胺

建立了同时测定羊肉制品中9种杂环胺的固相萃取-高效液相色谱(SPE-HPLC)分析方法。样品经2 mol/L NaOH超声提取、80 mL二氯甲烷液-液萃取,利用阳离子交换柱(MCX柱)净化和富集后进行HPLC分析。采用反相C18色谱柱,以乙腈和0.01 mol/L磷酸溶液(用三乙胺调整pH 3.6)为流动相对杂环胺进行梯度洗脱,使用二极管阵列检测器(DAD)分别在228 nm(2-氨基-9H-吡啶并［2,3-b］吲哚(AaC)、2-氨基-3-甲基-9H-吡啶并［2,3-b］吲哚(MeAaC))、253 nm(2-氨基-3-甲基咪唑并［4,5-f］喹啉(IQ)、1-甲基-9H-吡啶并［3,4-b］吲哚(Harman)、2-9H-吡啶并［3,4-b］吲哚(Norharman))、263 nm(2-氨基-3,8-二甲基咪唑并［4,5-f］喹喔啉(MeIQx)、2-氨基-3,4,8-三甲基咪唑并［4,5-f］喹喔啉(4,8-DiMeIQx)、3-氨基-1-甲基-5H-吡啶并［4,3-b］吲哚(Trp-p-2))、321 nm(2-氨基-1-甲基-6-苯基咪唑并［4,5-b］吡啶(PhIP))处进行检测。实验结果表明,9种杂环胺分离效果良好,回收率为50.27%～94.77%(n=6),相对标准偏差为0.08%～4.42%;通过全波长扫描,确定检出限(以信噪比(S/N)=3计)为1.6～41.0 μg/L。该方法操作简单,结果准确,重现性好,可用于同时检测羊肉制品中9种杂环胺的含量。     

UV-induced generation of rare tautomers of 2-thiouracils: a matrix isolation study

Unimolecular photoisomerization reactions were studied for 2-thiouracil, 6-aza-2-thiothymine, 1-methyl-2-thiouracil, and 3-methyl-2-thiouracil isolated in low-temperature Ar matrixes. The IR spectra have revealed that before UV irradiation all the matrix-isolated compounds adopted exclusively the oxo-thione tautomeric form. Upon UV (lambda > 320 nm) irradiation of the matrixes, two oxo-thiol photoproducts were generated for monomeric 2-thiouracil as well as for monomeric 6-aza-2-thiothymine. Generation of these products corresponds to transfer of a proton from either the N(1)-H or N(3)-H group to the sulfur atom of the C(2)=S thiocarbonyl moiety. The first of the above reactions was photoreversible. As a consequence, after prolonged UV irradiation most of the material was transformed into the oxo-thiol-N(1)H form. The hydroxy-thiol tautomers of 2-thiouracil and 6-aza-2-thiothymine were also photogenerated as minor products. For 1-methyl-2-thiouracil and 3-methyl-2-thiouracil, thione --> thiol phototautomeric reactions yielded the oxo-thiol isomers of the compounds. Since these reactions were photoreversible, the final stages of the photoinduced processes corresponded, for both methylated 2-thiouracils, to photostationary states. All the products of the investigated photoreactions were identified by comparison of their IR spectra with the spectra calculated at the DFT(B3LYP)/6-311++G(2d,p) level.     

Synthesis and autoxidation of new tetracyclic 9H,10H-indolizino[1,2-b]indole-1-ones.

The new tetracyclic 9H,10H-indolizino[1,2-b]indole-1-one derivatives (7a-d, 7ea, 7eb) have been synthesized by modified Fischer indole synthesis from the enol ether of 2,5-dihydroxy-7-methyl-6-cyano-indolizine (3) and arylhydrazines (4a-g). Attempted N-methylation of 7a-d produced a series of autoxidized products including 10-hydroperoxy-1-methoxyindolizino[1,2-b]indole (9a-d) as the major product accompanied with methylperoxides (10a-d and 11a-d) and 2-formyl-3-(pyridine-2-yl)indole (12a, 12c) derivatives as the minor products. A plausible mechanism of the autoxidation is postulated based on the isolation of some intermediates. The reaction is thought to proceed through azaenolate/enamine intermediates following a novel type of autoxidation.     

Mixed dimer and mixed trimer complexes of nBuLi and a chiral lithium amide

Multinuclear and multidimensional NMR spectroscopy have shown that lithium (S)-N-isopropyl-O-methyl-valinol (1-[6Li]) exists in a mixed 2:1 complex with nBu[6Li], (1-[6Li])2/nBu[6Li], in non-coordinating solvents such as hexane or toluene. A 6Li,1H-HOESY NMR spectrum indicates that the complex is a cyclic trimer with a large distance between the di-coordinated lithium and the carbanion of nBu[6Li]. Such arrangements are present in the solid state as previously reported by Williard and Sun. The exchange of lithium atoms within the trimer is slow at -33 degrees C. The exchange barrier (deltaG++) was determined to be 14.7 kcal x mol(-1) from quantitative 6Li,6Li-EXSY spectra. Addition of diethyl ether results in the formation of mixed dimers of (1-[6Li])/nBu[6Li], tetramers of nBu[6Li], and homodimers (1-[6Li])2. The apparent equilibrium constant of the mixed dimer was determined from the 6Li NMR integrals as K = 7.     

Reactivity of "Eu(OiPr)2" with phenols: formation of linear Eu3, square pyramidal Eu5, cubic Eu8, and capped cubic Eu9 polymetallic europium complexes

The direct reaction of europium with 2-propanol and phenols has been investigated under a variety of conditions. The reaction of europium metal with 2,6-dimethylphenol and 2,6-diisopropylphenol in 2-propanol at reflux revealed that polymetallic europium complexes could be generated by this method. Hx[Eu8O6(OC6H3Me2-2,6)12(OiPr)8], 1, and H5[Eu5O5(OC6H3iPr2-2,6)6(NCCH3)8], 2, were isolated by recrystallization in the presence of hexanes and acetonitrile, respectively, and characterized by X-ray crystallography. Complex 1 has a cubic arrangement of europium ions with face-bridging mu 4-O donor atoms, edge-bridging mu-O(phenoxide/phenol) ligands, and terminal O(isopropoxide/2-propanol) ligands. Complex 2 is mixed valent and has a square pyramidal europium core with four Eu(II) ions at the basal positions and one Eu(III) ion at the apex. Since these reactions gave complicated mixtures of products from which 1 and 2 could only be obtained in low yields, direct reactions under less forcing reaction conditions were investigated. Europium reacts slowly at room temperature to form arene-soluble divalent [Eu(OiPr)2(THF)x]n, 3. Complex 3 reacts with 2,6-dimethylphenol to form the arene-insoluble complex (H[Eu(OC6H3Me2)2(OiPr)])n, 4. Recrystallization of 4 in the presence of THF results in the crystallographically characterizable divalent trimetallic complex [Eu(OC6H3Me2-2,6)2(THF)2]3, 5, which has an unusual linear metal geometry. In the presence of HOiPr at ambient conditions in the glovebox, crystals of 5 slowly convert to the mixed valent H10[Eu8O8(OC6H3Me2-2,6)10(OiPr)2(THF)6], 6, which was found to have a cubic arrangement of europium atoms similar to 1 by X-ray crystallography. Complex 4, upon heating under vacuum, followed by reaction with THF, forms the arene-soluble divalent complex H18([Eu9O8(OC6H3Me2-2,6)10(THF)7][Eu9O9(OC6H3Me2-2,6)10(THF)6]), 7, which contains two types of capped cubic arrangements of europium ions in the solid state.