3-硝基-2-氨基苯甲酸的合成

以邻苯二甲酸酐为起始原料,经硝化、脱水、酰胺化、霍夫曼重排4步反应合成了3-硝基-2-氨基苯甲酸,总收率19%,其结构经1H NMR, IR和元素分析表征.探讨了酰胺化和霍夫曼重排反应条件对产率的影响.结果表明, n(脲素) ∶ n(3-硝基邻苯二甲酸酐)=2.0 ∶ 1.0,于50 ℃～60 ℃反应5 h～6 h,酰胺化反应收率85%～91%.n(NaClO) ∶ n(3-硝基-2-甲酰胺基苯甲酸)=1.2 ∶ 1.0,于60 ℃反应3 h,重排反应收率94%.     

合成2-(三溴甲磺酰基)吡啶的工艺改进

聚乙二醇-400催化2-氯吡啶(1)与甲硫醇钠反应合成了2-甲硫基吡啶(2);2与次溴酸钠经氧化和溴化反应合成了2-三溴甲磺酰吡啶(3),其结构经1H NMR,IR和元素分析确证。合成2的最佳反应条件为:1 100mmol,甲硫醇钠0.12 mol,聚乙二醇-400(1.2 mL)为催化剂,于80℃反应4 h,收率98%。合成3的最佳反应条件为:2 95 mmol,n(2)∶n(溴素)=1.00∶6.58,于8℃反应5 h,收率95.1%,纯度99.6%。     

硫酸氢钾催化一锅法合成1-乙酰胺烷基-2-萘酚

以硫酸氢钾为催化剂,在无溶剂条件下催化2-萘酚和乙酰胺分别与苯甲醛、对硝基苯甲醛、水杨醛、茴香醛、香兰素等五种芳香醛的三组分反应,利用一锅法合成了系列1-乙酰胺烷基-2-萘酚.以1-乙酰胺基苯甲基-2-萘酚(AAN)的合成为模板反应考察了催化剂用量、反应温度、原料配比及反应时间等因素对产物收率的影响.结果表明,硫酸氢钾催化合成AAN反应的适宜条件为:n(2-萘酚)∶n(苯甲醛)∶n(乙酰胺)∶n(硫酸氢钾)=1∶1.2∶1.2∶0.05,90℃下反应40min,AAN的收率达92.1%.硫酸氢钾对其他四种反应也有较理想的催化作用,目标产物收率为69.1%～94.0%.     

一种高分子紫外光吸收剂的合成研究

以2-(2-羟基-5-甲基苯基)苯并三唑、聚缩醛和哌嗪为原料,在乙二醇二甲醚溶剂中,经Mannich反应合成1,4-二[2-(2-羟基-5-甲基苯基)苯并三氮唑]哌嗪,确定了较佳缩合工艺条件。考察了物料配比、反应温度和时间对反应收率的影响,并经过正交实验,确定了反应的最佳工艺条件:在乙二醇二甲醚溶剂中,反应温度95℃,反应时间为24 h,n(2-(2-羟基-5-甲基苯基)苯并三唑)/n(HCHO)/n(哌嗪)=1.0∶1.5∶0.7,产品收率为82%,纯度98%(HPLC面积归一化法)。产品结构经IR、MS和1H-NMR表征。     

呋咱并[3,4-e]-4,6-二氧化-1,2,3,4-四嗪新法合成与表征

自行设计了呋咱并[3,4-e]-1,2,3,4-四嗪-4,6-二氧化(FTDO)新的合成路线,采用3,4-二氨基呋咱(DAF)为起始原料,经过氧化﹑缩合﹑硝化﹑成环4步反应合成了FTDO,总收率为30.89%,并采用核磁共振光谱﹑红外光谱﹑质谱及元素分析等进行了结构表征.探讨了成环反应的机理,并研究了硝化及成环反应条件,确定硝化反应的最佳条件为:硝化试剂为100%HNO3,25℃下反应2 h,收率为99.54%;成环反应的最佳条件为:55℃下反应5 h,n(化合物4)∶n(P2O5)为1∶16,溶剂量为160 mL/g,收率为46.37%.     

1-苯基-2-丙酮的合成新方法

以苯胺为原料,经重氮化反应和改进的Meerwein芳基化反应合成了1-苯基-2-丙酮(2)。优化的Meer-wein芳基化反应条件为:醋酸异丙烯酯为溶剂,氧化亚铜为催化剂,n(氟硼酸重氮盐)∶n(氧化亚铜)=10∶1,反应温度35℃~40℃,反应时间6 h。在优化反应条件下,2的收率达91%。     

2,5-二甲氧基-4-[(1E)-2-(1H-苯并咪唑-2-基)乙烯基]苯甲醛的合成

以2-甲基苯并咪唑(1)和2,5-二甲氧基-1,4-对苯二甲醛(3)为原料,经缩合反应合成了新化合物——2,5-二甲氧基-4-[(1E) -2-( 1H-苯并咪唑-2-基)乙烯基]苯甲醛(4),其结构经1H NMR,IR和ESI-MS表征.较佳缩合反应条件为:1 11 mol,n(1)∶n(3)=1.1∶1.0,回流反应6h,收率75.2％.     

合成3-(2-吡啶氨基)丙酸乙酯的工艺改进

以2-氨基吡啶(2)和丙烯酸乙酯(3)为起始原料,经一步反应合成了凝血酶因子抑制剂达比加群酯的关键中间体3-(2-吡啶氨基)丙酸乙酯,其结构经1H NMR和ESI-MS确证.最佳反应条件为:2 120 mmol,n(2)∶n(3) =1.00∶1.08,于100℃回流反应24h,收率79.6％.     

2α-甲基-2β-溴甲基青霉烷酸二苯甲酯的合成

以6,6-二氢青霉烷酸二苯甲酯-1-氧化物(Ⅰ)和2-巯基苯并噻唑为原料,通过热裂解开环反应和溴代环合反应,制备得到了β-内酰胺酶抑制剂他唑巴坦关键中间体2α-甲基-2β-溴甲基青霉烷酸二苯甲酯(Ⅲ)。考察了反应温度、反应时间、物料比、催化剂用量对目标产物的影响。结果表明,在n(Ⅱ)∶n(HBr)∶n(Na NO_2)=1∶3∶6,催化剂质量分数为4%,-5℃反应2. 5h的条件下,收率为85. 4%。产物结构经1HNMR、FTIR、MS等技术手段得到验证。     

杂多酸盐催化合成碳酸丙烯酯

以杂多酸盐为催化剂,尿素(1)和1,2-丙二醇(2)为原料合成了碳酸丙烯酯.考察了不同杂多酸盐的催化活性和影响反应的因素.较适宜的反应条件为: 1 500 mmol, n(1) ∶ n(2)=1 ∶ 2, w(钨硅酸锌)=2.0%,于165 ℃反应6 h,收率97.32%.硅钨酸锌重复使用5次后,收率仍高于90%.     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

A general and convenient synthesis of 4-(tosylmethyl)semicarbazones and their use in amidoalkylation of hydrogen,heteroatom, and carbon nucleophiles

A general synthesis of previously unknown semicarbazone-based α-amidoalkylating reagents, 4-(tosylmethyl)semicarbazones, has been developed. The synthesis involved three-component condensation of semicarbazones of aliphatic or aromatic aldehydes with the same or other aldehydes and p-toluenesulfinic acid. The scope and limitations of this reaction were investigated. The compounds obtained were demonstrated to be an efficient α-(4-semicarbazono)alkylating agents. They were reacted with H- (sodium borohydride), O- (sodium methylate), S- (sodium phenylthiolate), N- (pyrrolidine, sodium succinimide), P- (trialkyl phosphites), and C-nucleophiles (sodium diethyl malonate) to give the corresponding products of the tosyl group substitution, 4-substituted semicarbazones, including analogues of nitrofurazone. Among the prepared compounds tested in vitro for antibacterial and antifungal activity, three nitrofuryl-containing semicarbazones exhibited high biological activities with minimum inhibitory concentration (MIC) values of 8–32 μg/mL.     

Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki–Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.