合成乙拉西坦的方法改进

以2-吡咯烷酮为起始原料,经成盐与缩合反应合成了乙拉西坦,总收率60.2%.其结构经1H NMR, IR和MS确证.     

液相色谱–质谱法测定血清中左乙拉西坦含量

建立测定血清中左乙拉西坦浓度的液相色谱–质谱方法。血清样品用甲醇提取,离心分离除去蛋白,采用液相色谱–质谱法测定其中左乙拉西坦的含量。流动相为甲醇–0.1%甲酸(体积比为80∶20),色谱柱为Agilent C18柱(100 mm×4.6 mm,3.5μm)。左乙拉西坦含量在1 000~100 000 ng/m L范围内与色谱峰面积线性关系良好,线性相关系数r2=0.999,检出限为10 ng/m L。测定结果的相对标准偏差为0.93%(n=6),样品加标回收率为99.4%~101.3%。该方法具有较高的灵敏度、准确度和良好的精密度,适合血清中左乙拉西坦含量的测定。     

乙拉西坦的合成

2-吡咯烷酮经N-烷基化、氨解反应合成了乙拉西坦,总收率42．6％。其结构经^1H NMR,^13C NMR和IR表征。     

离子色谱-电导检测法测定左乙拉西坦中四丁基溴化铵残留

建立了左乙拉西坦原料药中痕量四丁基溴化铵测定的离子色谱方法。以Dionex IonPac CS17阳离子交换色谱柱为分析柱,15 mmol/L甲磺酸溶液-乙腈淋洗液,流速为1.0 mL/min,抑制型电导检测器。样品基质及常见阳离子对测定无干扰,四丁基溴化铵质量浓度在0.5～20 mg/L范围内与峰面积线性关系良好,相关系数为0.9997,定量限(LOQ)为0.5 mg/L,检出限(LOD)为0.15 mg/L,加标回收率为98.0%～103.7%。方法可用于左乙拉西坦原料药中痕量四丁基溴化铵的检测。     

一种新型荧烷染料的合成

以间二乙氨基苯酚(1)和邻苯二甲酸酐(2)为原料制得2一羧基-4'-二乙氨基-2'-羟基二苯甲酮(3);在浓硫酸作用下,3与2-甲基-5-对甲氧基苯基-1,3,4-噁二唑(4)反应合成了一种新型的荧烷染料--2-(5-甲基-1,3,4-噁二唑-2-基)-6-二乙氨基荧烷,其结构经1H NMR,IR和元素分析表征.合成3的较适宜条件为:132mmol,n(1):n(2)=1.0:1.2,36%NaOH 60 mL,反应时间10 h,分解时间6 h,收率71.8%,纯度83.4%(HPLC).     

新型苯乙酰脒类化合物的合成及其感光性能

以氢化铝锂为还原剂,甲基叔丁基醚为溶剂,1,5-二氮杂双环[4.3.0]-5-壬烯(1)于55℃反应9 h制得1,5-二氮杂双环[4.3.0]壬烷(2),收率87.9%,纯度95.0%。2分别与溴代苯乙酮(3a),对甲氧基溴代苯乙酮(3b)和对溴基溴代苯乙酮(3c)进行消除反应合成了3个新型的苯乙酰基潜双环脒类化合物(4a~4c),其结构经1H NMR和LC-MS表征。采用正交实验对合成4a~4c的反应条件进行了优化。在最佳反应条件[以甲苯为溶剂,3a 25.2 mmol,n(3a)∶n(K2CO3)∶n(2)=1.0∶2.0∶1.4,于15℃反应24 h]下,1,5-二氮杂双环[4.3.0]-5-苯乙酰基壬烷(4a)收率89.0%,纯度87.9%。感光性能研究结果表明,1,5-二氮杂双环[4.3.0]-5-(4-甲氧基)苯乙酰基壬烷(4b)经紫外曝光400 mJ·cm-1,其引发性能最强,分解转化近45%;曝光2 000 mJ·cm-1,4b分解转化近90%。     

3-氯-5-(三氟甲基)-2-乙胺基吡啶的合成

以2,3-二氯-5-三氟甲基吡啶为起始原料,经亲核取代、脱羧、加氢还原及酰胺水解等4步反应合成了3-氯-5-(三氟甲基)-2-乙胺基吡啶,纯度97.4%,总收率61.36%,其结构经1H NMR确证。     

一种合成拉坦前列素的新方法

拉坦前列素是治疗青光眼和高眼压症的首选药物.现有合成方法存在路线长、收率低、异构体杂质难以分离等问题.本研究以苯甲酰基科里内酯为原料,氧化后与2-氧代-4-苯丁基膦酸二甲酯通过改良Horner-Wadsworth-Emmons反应形成ω侧链,经还原、脱保护、氢化、四氢吡喃基(THP)保护、还原内酯得到内半缩醛,然后以(4-羧基丁基)三苯基溴化鏻与六甲基二硅基胺基钠(NaHMDS)形成磷叶立德通过Wittig反应形成α侧链,经酯化、脱保护基后,合成了拉坦前列素,并用正相液相色谱法纯化,制得终产物,产物用1H NMR,13C NMR,IR和HRMS进行了结构表征.结果表明,拉坦前列素纯度达99.91%,总收率为19.2%.为拉坦前列素的合成提供一种高收率、高纯度、可大批量合成的新方法.     

HPLC法测定(S)-2-氨基丁酰胺对映异构体

使用高效液相色谱-柱前衍生化法测定了(S)-2-氨基丁酰胺盐酸盐的对映异构体。采用梯度洗脱;流动相A为0.1 mol/L乙酸铵溶液,流动相B为乙腈溶液;流速1.5 m L/min;波长336 nm;柱温为40℃。(S)-2-氨基丁酰胺盐酸盐对映异构体的检出限和定量限分别为0.0085μg/m L和0.0319μg/m L。对映异构体的浓度在0.03~3.0μg/m L范围内线性关系良好(r2=0.9992),回收率在91.8%~104.6%之间。方法能够有效控制左乙拉西坦重要中间体(S)-2-氨基丁酰胺的光学纯度。     

2,3-二甲基-4-氯吡啶-N-氧化物的合成工艺改进

对2,3-二甲基-4-氯吡啶-N-氧化物(4)的合成工艺进行了改进。以2,3-二甲基吡啶为原料,经氧化(钨酸钠为催化剂,双氧水为氧化剂,收率96.5%),硝化(65%的浓硝酸为硝化剂,收率86.3%,纯度99.0%)及氯化(乙酰氯为氯化剂,收率86.8%,纯度98.6%)合成了4,总收率72.2%,4的结构经1H NMR表征。     

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.     

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.     

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.     

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.     

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.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Microwave-assisted copper-catalyzed stereoselective ring expansion of three-membered heterocycles with α-diazo-β-dicarbonyl compounds

Microwave-assisted copper-catalyzed ring expansions of three-membered heterocycles with α-diazo-β-dicarbonyl compounds were investigated. Thiiranes generated 3-acyl-5,6-dihydro-1,4-oxathiines in the presence of copper sulfate and trans-3-acyl-5,6-dihydro-1,4-oxathiines as stereospecific products for 1,2-disubstituted cis-thiiranes through an intramolecular S_N2 process. Oxiranes gave rise to 2-acyl-5,6-dihydro-1,4-dioxines under the catalysis of copper hexafluoroacetylacetonate and cis-3-acyl-5,6-dihydro-1,4-dioxines as stereospecific products for 1,2-disubstituted cis-oxiranes via an intimate ion-pair mechanism. The current method provides a direct and simple strategy in efficient preparation of 3-acyl-5,6-dihydro-1,4-oxathiines and 2-acyl-5,6-dihydro-1,4-dioxines, important agents in medicinal and agricultural chemistry, from readily available thiiranes and oxiranes, respectively.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.