新型1,3,4-噁二唑-2-硫酮衍生物的合成及其抗肿瘤活性

以手性氨基酸和间甲基苯甲酸(或苯乙酸)为原料,经酯化、缩合、肼解和环合反应合成了12个新型的1,3,4-噁二唑-2-硫酮衍生物(6a~6f或7a~7f),其结构经1H NMR,FT-IR和ESI-MS表征。用MTT法研究了6和7的抗肿瘤活性。结果表明:(2S)-5-(3-甲基苯甲酰胺基)苯乙基-1,3,4-噁二唑-2-硫酮(6f)和(2S)-5-(2-羟基-苯乙酰胺基)乙基-1,3,4-噁二唑-2-硫酮(7b)对红白血病细胞(K562)抑制活性较好。     

2,2′-联吡啶取代的1,3,4-噁二唑硫醚的合成及晶体结构

利用基团拼合原理,将2,2′-联吡啶和硫醚结构引入到1,3,4-噁二唑母体结构中.以1,10-菲罗啉为原料,经过氧化、酯化、肼解以及环合等化学反应,合成了中间体2,2′-联吡啶-3,3′-二甲酰肼、2,2′-联吡啶-3,3′-二(5-[1,3,4-噁二唑-2-硫酮])以及4个2,2′-联吡啶-3,3′-二(5-[1,3,4-噁二唑-2-硫醚])系列目标化合物,其结构通过1 H NMR和单晶X-射线衍射等进行表征.晶体结构分析表明:2,2′-联吡啶的3和3′位上取代基不同,2个吡啶环所在平面的偏转角度不同,1,3,4-噁二唑-2-硫醚结构能使2个吡啶环呈现较大的偏转角度.     

含1,3,4-噁二唑和1,3,4-噻二唑的硫醚类化合物的合成

在KOH作用下,芳甲酰肼1a～1e与CS2环化生成5-芳基-2-巯基-1,3,4-噁二唑(2a～2e);将2a～2e与氯乙酸乙酯反应,生成2-(5-芳基-1,3,4-噁二唑)硫基乙酸乙酯(3a～3e);3a～3e肼解得2-(5-苯基-1,3,4-噁二唑-2-硫基)乙酰肼(4a～4e);4a～4e与芳酰基异硫氰酸酯5a～5d反应得到双酰基氨基硫脲衍生物A1～A19;A1～A19在H2SO4催化下环合得到目标化合物B1～B19;目标化合物的结构经IR,1H NMR,MS,HRMS确证.     

2,5-取代-1,3,4-噁二唑衍生物的合成与杀菌活性

利用生物活性亚结构拼接原理,将吡啶环、噻唑环引入到1,3,4-噁二唑母体结构中,设计并合成了一系列新型含吡啶(噻唑)的1,3,4-噁二唑衍生物.通过IR,1H NMR,EI-MS及元素分析等方法对所合成的化合物进行了结构表征.代表化合物2-(6-氯吡啶-3-甲硫基)-5-(吡啶-4-基)-1,3,4-噁二唑(I)经单晶X衍射证实了结构.初步测定了所合成化合物的杀菌活性,并比较了在1,3,4-噁二唑母体结构中引入噻唑杂环和引入吡啶杂环后其杀菌活性的差异.结果表明:目标化合物对测试的5种菌均具有一定的杀菌活性,对水稻纹枯病的抑制效果普遍优于对其它菌种的抑制效果;在1,3,4-噁二唑母体结构中引入噻唑杂环比引入吡啶杂环对其杀菌活性更有利.     

5-(4-氟苯基)-1,3,4-噁二唑-2-巯基乙酰腙类化合物的合成、表征及生物活性

以4-氟苯甲酸为原料,经过酯化、肼解、关环生成5-(4-氟苯基)-1,3,4-噁二唑-2-硫酮,再与溴乙酸乙酯、水合肼反应得到中间体2-[(4-氟苯基)-1,3,4-噁二唑-2-硫基]-乙酰肼,最后中间体酰肼与取代苯甲醛在冰乙酸中回流得到一系列含有1,3,4-噁二唑环的乙酰腙类化合物。目标化合物结构经元素分析、IR、1H NMR、ESI-MS得到确证,并通过K-B纸片法初步测定了它们的生物活性。结果表明,部分化合物具有一定的抑菌活性。     

新型含异噁唑环1,3,4-噁二唑啉衍生物的合成

以N-羟基-4-甲氧基苯甲醛肟氯化物为原料,经两步反应制得3-对甲氧基苯基-5-甲基-异噁唑-4-甲酰肼(3);3依次经缩合和环合反应合成了一系列新型的2-芳基3-乙酰基-5-(3-对甲氧基苯基-5-甲基-异噁唑-4-基)-Δ4-1,3,4-噁二唑啉衍生物,其结构经~1H NMR,13C NMR,IR,MS(EI)和元素分析表征。     

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).     

2,5-二取代-1,3,4-噻二唑衍生物的合成与表征

苯并噁唑啉酮和1,3,4-噻二唑衍生物具有多种生物活性,制备含有苯并噁唑啉酮结构的1,3,4-噻二唑衍生物非常有意义。本文以邻氨基苯酚和尿素为初始原料,经多步合成反应,制备了10个新的2-(芳甲酰氨基)-5-(2-苯并噁唑啉酮-3-甲基)-1,3,4-噻二唑化合物(7a～7j),并利用IR、1H NMR和元素分析对其结构进行了表征。     

(3-苄基-4-芳酰基-1,2,4-三唑-5-基)(5-本基-1,3,4-噁二唑-2-基)硫醚的合成

通过3-苄基-4-芳酰基-1,2,4-三唑-5-巯基负离子在2-甲磺酰基-5-苯基-1,3,4-噁二唑环2-位上的亲核取代反应,制得13个新的(3-苄基-4-芳酰基-1,2,4-三唑-5-基)(5-苯基-1,3,4-噁二唑-2-基)硫醚衍生物.经元素分析、IR、~1H NMR和MS裂解碎片分析确认结构.初步观察了它们在0.01％浓度时对大肠杆菌繁殖的抑制作用.     

N′-（5-芳基-1,3,4-噁二唑-2-基）-N-（邻苯磺酰甲酰亚胺乙酰基）硫脲的合成及抑菌活性

将邻苯甲酰磺酰亚胺、1,3,4-噁二唑2个杂环同时引入到酰基硫脲中,合成了12种新的N-′（5-芳基-1,3,4-噁二唑-2-基）-N-（邻苯磺酰甲酰亚胺乙酰基）硫脲化合物,化合物的结构均经元素分析、1H NMR和IR等测试技术得以确证。抑菌法生物活性测试结果表明,大部分化合物对黄瓜灰霉病菌、油菜菌核病菌抑制效果很好,特别是化合物5b和5l对5种病菌抑制率均在87%以上,有的病菌抑制率达到100%。     

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.