2,3a-二氢-苯并吡喃[4,3-c]吡唑-3-酮类衍生物的合成及其活性

为了进一步寻找新型黄酮类农药,以苯并吡喃[4,3-c]并吡唑-3-酮为先导结构,以4-氯苯甲醚为起始原料.设计合成了33种新型的2,3a-二苯并吡喃[4,3.c]吡唑-3-酮类化合物,其结构经MS,~1H NMR和元素分析确证.并对化合物7k的单晶进行了结构测定,对目标化合物进行了杀虫和杀菌活性测试.结果表明,大部分化合物显示出一定的杀菌活性和弱的杀虫活性.     

1,4-二氨基-3,6-二硝基吡唑[4,3-c]并吡唑的合成、热性能及量子化学研究

以自制的3,5-二甲基-4-氨基吡唑为原料,经重氮化、环化、硝化、氧化、脱羧硝化以及N-胺化等反应合成了1,4-二氨基-3,6-二硝基吡唑[4,3-c]并吡唑(LLM-119),采用红外光谱、核磁共振、质谱及元素分析等手段表征了中间体及目标物的结构;对4-重氮基-3,5-二甲基吡唑内盐的后处理方法进行了改进,采用冷冻结晶法代替萃取法,避免大量使用有机试剂,简化操作过程,收率由77.0%提高到86.1%;初步探讨了N-胺化反应的机理,从理论上分析了收率偏低的原因;利用DSC,TG等热分析手段研究了LLM-119的热性能,其热分解峰温为232.05℃,表明LLM-119具有较好的热稳定性;首次采用B3LYP方法,在6-31G(d,p)基组水平上对LLM-119的结构进行了全参数优化,获得其稳定的几何构型和键级;在振动分析的基础上求得体系的振动频率、IR谱及不同温度下的热力学性质,并得到了温度对热力学性能影响的关系式;用Monte-Carlo方法从理论上计算LLM-119的密度为1.85 g/cm3,与实验值接近,运用Kamlet公式预测爆速为8733.94 m/s.     

3-甲基-5-氰基-6-氨基-1-苯基-4-(3,4-二甲氧基苯基)-1,4-二氢吡喃[2,3-c]吡唑的合成和晶体结构

标题化合物C22H20N4O3 3是由2-氰基-3-(3,4-二甲氧基苯基)丙烯腈1和3-甲基-1-苯基-2-吡唑-5-酮2在KF-Al2O3催化下在N,N-二甲基甲酰胺(DMF)溶剂中反应而得。结构通过单晶X-射线衍射分析确定,其晶体属于三斜晶系,空间群Pī,a = 9.450(3),b = 10.876(2), c = 11.435(2) ,a = 115.51(1), b = 102.82(1),g = 98.47(2), Mr = 388.42, V = 994.1(3) 3,Dc = 1.298 g/cm3, Z = 2, m (MoKa) = 0.089 mm-1, F(000) = 408。晶体结构用直接法解出,使用全矩阵最小二乘法对原子参数进行修正,最后的偏离因子R = 0.0420,wR = 0.1070。单晶X-射线衍射分析表明平面Ⅰ与平面Ⅱ、平面Ⅲ、平面Ⅳ的夹角分别为102.31、29.24和1.43。平面Ⅱ与平面Ⅲ和平面Ⅳ的夹角分别为73.50和100.91,平面Ⅲ和平面Ⅳ的夹角为27.81, 另外晶体中还存在分子间氢键。     

10-氯-5-二乙氧基甲基-1,3-二甲基色烯并[4,3-d]吡唑并[3,4-b]吡啶-6(3H)-酮的合成和晶体结构

利用L-脯氨酸催化的5-氯水杨醛(1)与6-甲基-4-羟基吡喃酮(2)的缩合反应及硫酸铜催化下与1,3-二甲基-5-氨基吡唑(3)的串联反应,合成得到了10-氯-1,3-二甲基-5-(2-氧代丙基)色烯并[4,3-d]吡唑并[3,4-b]吡啶-6(3H)-酮(4)和10-氯-5-二乙氧基甲基-1,3-二甲基色烯并[4,3-d]吡唑并[3,4-b]吡啶-6(3H)-酮(5).化合物5的结构通过单晶X射线衍射法确定:晶体属于三斜晶系,空间群P-1;相对分子质量Mr=803.68;晶胞参数a=1.03160(10)nm,b=1.42900(13)nm,c=1.44268(15)nm;V=1.9448(3)nm~3;Z=2;晶胞密度Dc=1.372g/cm~3;吸收系数μ=0.228mm-1;单胞中电子的数目F(000)=840.晶体结构用直接法解出,经全矩阵最小二乘法对原子参数进行修正,最终的偏离因子为R=0.0681,w R=0.2051.在晶体结构中色烯环与吡啶环及吡唑环近似于共平面.     

3-亚甲基苯并吡喃-2,4-二酮与烯醇硅醚的Diels-Alder反应合成3,4- 二氢-2H,5H-吡喃并[3,2-c][1]苯并吡喃-5-酮衍生物

通过4-羟基香豆素与苯甲醛、甲醛和戊醛缩合产生的quinone methide与烯醇硅醚的Diels-Alder反应, 以较高产率合成了一系列含有硅氧基的3,4-二氢-2H,5H-吡喃并[3,2-c][1]苯并吡喃-5-酮衍生物. 用X射线单晶衍射确定了其中5个化合物的空间构型. 利用密度泛函(DFT)方法计算反应物之间的前线分子轨道相互作用, 对反应的区域选择性进行了研究, 计算结果与实验值相符.     

超声作用下四组分一锅法合成二氢吡喃并[2,3-c]吡唑衍生物

报道了在超声波作用下,乙醇作溶剂,无任何催化剂下由醛、水合肼、乙酰乙酸乙酯(或丁酰乙酸乙酯)和丙二腈四组分简单、方便、有效地合成了一系列二氢吡喃并[2,3-c]吡唑衍生物.该方法具有产物产率高、反应时间短、条件温和及操作简单的优点.     

四氢吡啶并[4,3-d]二氢嘧啶酮衍生物的合成及其初步抗癌活性测定

为寻找新型抗癌药物的先导化合物,设计合成了16种未见文献报道的四氢吡啶并[4,3-d]二氢嘧啶酮衍生物2a～2p,结构经1H NMR,IR,MS,元素分析确证.初步的生物活性测试结果表明,在100μg/mL浓度下,目标化合物对白血病K562细胞的增殖表现出显著的抑制活性,对卵巢癌HO-8910和肝癌SMMC-7721细胞系的增殖也表现出一定的抑制活性.     

四组分一锅法合成多取代吡喃[2,3-c]吡唑-5-腈

在三乙胺催化下,以乙酰乙酸甲酯、苯肼、芳醛和丙二腈等4组分为原料,经一锅法合成了一系列多取代的吡喃并[2,3-c]吡唑衍生物(5a～5j),反应在10～15 min内即可完成.所有产物由IR、1HNMR和MS确证.该方法具有产率高、操作简单等优点.     

2-氨基-3-氰基-4-(4-氟苯基)-4H-苯并[h]苯并吡喃的合成和晶体结构

标题化合物与N,N-二甲基甲酰胺(DMF)形成的1:1混合结晶物C20H23FN2OC3H7NO由对氟苯甲醛、丙二腈、-萘酚在六氢吡啶存在下合成并经DMF与水的混合溶剂重结晶而得, 其结构通过元素分析、IR 和1H NMR对化合物进行了表征,用X-射线单晶衍射法测定了该化合物的晶体结构。结果表明,晶体属于单斜晶系,P21/n空间群,a = 6.365(1), b = 10.620(2), c = 29.122(6) ? b = 92.00(1), V = 1967.3(6) ?, Mr = 389.42, Z = 4, Dc = 1.315 g/cm3, m (MoKa) = 0.092 mm-1, F(000) = 816。晶体结构用直接法解出,经全矩阵最小二乘法修正,最终偏离因子R = 0.047, wR = 0.1053。化合物分子中,原子C(1), C(2), C(3), C(4), C(5) 和O(1)形成1个六员环,该六员环中C(1)C(2)键长为1.346(3) 牛砻魑肆被肺焦瓜蟆?     

L-脯氨酸催化一锅法合成4 H-吡喃并[2,3-c]吡唑衍生物

以L-脯氨酸为绿色催化剂,3-甲基-5-吡唑酮(或1-苯基取代物)和芳醛及丙二腈为原料,就微波辅助的一锅法成环缩合反应进行研究。实验结果表明,乙醇/水为溶剂,催化剂用量10mol%,微波功率300W和80℃下反应10～15 min,即可得到4H-吡喃并[2,3-c]吡唑类化合物(4a～4j),合成收率达85～94%。该方法具有产率高、反应时间短、操作简单等优点。     

Synthesis and Crystal Structure of 2-Ethoxycarbonylmethyl-8-chloro-3a,4-dihydro-3a-methyl-chromeno[4,3-c]pyrazol-3（2H）-one

The crystal structure of the title compound 2-ethoxycarbonylmethyl-8-chloro-3a,4-dihydro-3a-methyl-chromeno[4,3-c]pyrazol-3(2H)-one(C15H15ClN2O4,Mr = 322.74) has been prepared and determined by single-crystal X-ray diffraction.The crystal is of orthorhombic,space group Pccn with a = 16.7246(10),b = 19.6626(12),c = 9.3013(6) ,V = 3058.7(3) 3,Z = 8,Dc = 1.402 g/cm3,μ = 0.269 mm-1,F(000) = 1344,the final R = 0.0506 and wR = 0.1464 for 2568 reflections with I 2σ(I).In addition,disordered C(14) and C(15) atoms exist in the crystal structure.     

Synthesis and mesomorphic properties of 7-alkoxybezopyrano[2,3-c]pyrazol-3-one

A new series of fused polyheterocyclic aromatic compounds, 7-alkoxybezopyrano[2,3-c]pyrazol-3-one (C- n BPP), were synthesised and characterised by infrared, ¹H-nuclear magnetic resonance (NMR), ¹³C-NMR and two-dimensional ¹H-¹³C cosy spectra. Their phase transition behaviour was investigated by differential scanning calorimetry and polarising optical microscopy. All of these compounds showed enantiotropic mesophases with temperature domains of 12–60°C and 22–69°C on heating and cooling processes for a carbon number of the alkoxy chain from 2 to 10. The effect of the length of the alkoxy chain on the mesomorphic properties was discussed. Comparison of C- n BPP and several kinds of coumarin derivatives indicated that the intermolecular hydrogen bonding acted as the driving force of the mesophase formation.     

新型2-氨基-呋喃并[2,3-d]嘧啶-4(3H)-酮衍生物的合成及抗肿瘤活性

报道应用aza-Wittig反应,采用易得的原料,在温和的条件下,以78%～90%的产率有效的合成了新型2-氨基-呋喃并[3,2-d]嘧啶-4(3H)-酮衍生物5,其结构经IR,1H NMR,MS和元素分析确认.为进一步得到结构确认,化合物5c经X射线衍射分析证实.运用噻唑蓝(MTT)标准法对化合物5进行了体外抗肿瘤活性的测定,其中5f对肺癌细胞A459的IC50值为18.4μmol/L,显示出潜在良好的抗肿瘤活性.     

Catalyst-free three-component approach to efficient synthesis of chromeno[4,3-b]pyrrol-4(1H)-one derivatives

A mild, efficient, and environmentally benign one-pot synthesis of functionalized chromeno[4,3-b]pyrrol-4(1H)-ones by a three-component domino reaction of 4-aminocoumarins, arylglyoxal monohydrates, and 1,3-dicarbonyl compounds in refluxing ethanol without the use of catalyst is reported. The present protocol features operational simplicity, short reaction time, good yields, and the absence of aqueous workup procedure and chromatographic separation.     

Synthesis and Crystal Structure of 2-Ethoxy-3-n-butyl-benzofuro[2,3-d]pyrimidin-4（3H）-one

The crystal structure of the new title compound 2-ethoxy-3-n-butyl- benzofuro[2,3d]pyrimidin-4（3H）-one （C16H18N2O3, Mr = 286.32） has been prepared and determined by singlecrystal X-ray diffraction. The crystal is of monoclinic, space group P21/c with a = 13.7167（14）, b = 13.113（1）, c = 8.378（1） A, β = 98.992（2）^o, V = 1488.4（3） A^3, Z = 4, Dc = 1.278, F（000） = 608, μ = 0.089 mm^-1, MoKa radiation （2 = 0.71073）, R = 0.0498, wR = 0.1238 for 2336 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals that all ring atoms in the benzo[4, 5]furo [2,3-d] pyrimi- dinone moieties are almost coplanar.     

Synthesis of (1H)-3,4-Dihydropyrrolo[2,1-c][1,4]oxazin-1-one Derivatives

It has been found that some acyl derivatives of 1,2,3,4-tetrahydro-1-indolizin-1-one 1and (1H)-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one 2 show remarkable anti-inflammatory and analgesic activities1,2. The interest in extending the study of structure-activity relationships and search of new potent anti-inflammatory and analgesic agents led us to design and synthesize (1H)-3,4-dihydropyrrolo[2,1-c][1,4]oxazin-1-one 3 derivatives. NO 1 NNHO2 87654321ONO3 A few examples of the p…     

Novel Synthesis of Thieno[2,3-c]Pyridazine and Pyrimido[4',5':4,5]thieno[2,3-c]pyridazine Derivatives

Abstract

Novel series of thieno[2,3-c]pyridazines and pyrimido[4′,5′:4,5] thieno-[2,3-c]pyridazines have been synthesized from the readily accessible 4-cyano-5,6-dimethylpyridazin-3(2H)-thione 3b.     

A NOVEL SYNTHESIS OF 2-SUBSTITUTED-4H-THIENO [2,3-d][1,3] OXAZIN-4-ONE AND 2,3-DISUBSTITUTED THIENO [2,3-d]PYRIMIDIN-4(3H)-ONE DERIVATIVES

Abstract

The synthesis of acetic 2-{[1-methyl-2-(4-oxo-5,6,7,8-tetrahydro-4H-benzo [4,5]-thieno [2,3-d] [1,3-oxazin-2-yl)ethylidene]amino}-4,5,6,7-tetrahydrohenzo[b]thiophene ?3-carboxylic acid anhydride 5 and 2-(oxopropyl)-5,6,7,8-tetrahydro-4H-benzo-[4,5] thieno[2,3-d][1,3]oxazin-4-one 7, has been achieved in three steps from ethyl 2-amino-4,5,6,7-tetrahydrobenzo(b]thiophene-3-carboxlate 1 via the reaction with ethyl acetoacetate followed by hydrolysis and acetic anhydride-induced cyclization. The 2-substituent in compound 5 has two functional groups i.e. active methylene and acid anhydride which are suitably located for intramolecular transformation. Thermal and/or base catalyzed intramolecular cyclization of 5 afforded 2-(4-acetoxy-(hydroxyl)-2-methyl-5,6,7,8-tetrahydrobenzo[4,5] thieno[2,3-b]pyridin-3-yl)-5,6,7,8- tetrahydro-4H-benzo[4,5]thieno[2,3-d] [1,3]oxazin-4-one 10 and 9 respectively. Treatment of 5 with hydrazine hydrate, aromatic and/or heterocyclic amines induced the same intramolecular cyclization with a concomitant oxazine-pyrimidine interconversion to give 3-amino(aryl or heteryl)-2-(4-hydroxy-5,6,7,8-tetrdhydrobenzo-[4,5]thieno[2,3-b]pyridin-3-yl)-3,4,5,6,7,8-hexahydrobenzo[4,5] thieno[2,3-d] pyrimid in-4-one 11–14 respectively.     

Synthesis,Antibacterial, and Antifungal Activities of Imidazo[2,1-c][1,2,4]triazoles and 1,2,4-Triazolo[4,3-a]pyrimidinones

A straightforward method has been developed for the synthesis of 1-phenyl-imidazo [2,1-c][1,2,4]triazole derivatives 5a–j and 1-phenyl-[1,2,4]triazolo[4,3-a]pyrimidinones derivatives 6a–g starting from 5-amino-1-phenyl[1,2,4]triazole and p-toluenesulfonic acid (PTSA). This methodology affords a number of 1-phenyl-imidazo [2,1-c][1,2,4]triazoles 5a–j and 1-phenyl-[1,2,4]triazolo[4,3-a]pyrimidinones 6a–g in reasonable yields and short reaction times. The structures of all new compounds were elucidated using infrared, ¹H and ¹³C NMR, and high-resolution mass spectrometry. Some of the newly synthesized compounds were screened for their antimicrobial activity.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications ^® for the following free supplemental resource(s): Full experimental and spectral details.]