取代-1,3-二氢吲哚-2-酮化合物的合成

取代苯胺经酰化、环合反应制得关键中间体取代靛红衍生物4a～4k,再用三乙基硅烷/三氟乙酸体系室温还原制得取代-1,3-二氢吲哚-2-酮类化合物1a～1k,后者可用于合成舒尼替尼等酪氨酸激酶抑制剂类抗肿瘤药.     

3,6-二甲氧基-2,5-二氢吡嗪-2-羧酸乙酯的合成

用苄氧羰基氨基乙酸在N-甲基吗啉的催化下与氯甲酸异丁酯反应后,无需分离直接与氨基丙二酸二乙酯盐酸盐反应得到(2-苄氧羰基氨基乙酰胺基)丙二酸二乙酯,经Pd/C催化氢解、环合后在二氯甲烷中与Me3OBF4反应制得α-取代丝氨酸的合成中间体3,6-二甲氧基-2,5-二氢吡嗪-2-羧酸乙酯,总收率35.1%.     

6-乙酰氨基-1,2,3,4-四氢-1-萘酮的合成

目的:合成中间体6-乙酰氨基-1,2,3,4-四氢-1-萘酮.方法:以苯甲酰基丙酸为原料,经过硝化、硝基还原、酰化、羰基还原、环合得到6-乙酰氨基-1,2,3,4-四氢-1-萘酮.结果与结论:只需经过5步反应就可以合成目标化合物,总收率14.7%.     

罗替戈汀手性中间体S(-)2-(N-正丙基)胺基-5-甲氧基四氢萘的合成

目的 合成罗替戈汀关键手性中间体S(-)2-(N-正丙基)胺基-5-甲氧基四氢萘.方法 以5-甲氧基-2-四氢萘酮为起始物,经过正丙胺胺化、10％钯炭催化氢化还原、手性拆分3个步骤合成得到该中间体.结果手性中间体S(-)2-(N-正丙基)胺基-5-甲氧基四氢萘的总收率为21.5％.结论该路线的原料廉价易得、收率高,...     

取代咪唑酮合成工艺研究

目的:优化取代咪唑酮类化合物的合成工艺.方法:采用正交设计法,重点考察反应溶剂,投料比例及温度对收率的影响.结果:投料比例对收率的影响最为显著.结论:使收率由低于10%提高到42.5%,使得更加符合工业生产的要求.     

新型喹唑啉酮类化合物合成工艺研究

目的 优化取代喹唑啉酮类化合物的合成工艺,重点考察温度、时间2个因素对关键中间体化合物合成的影响。 方法 平行试验比较温度、时间和缩合剂催化酯键的氨解反应,并对试验结果进行整体化分析;采用正交设计的方差分析考察反应物、温度及时间对收率的影响。 结果和结论 所得化合物的结构经过¹H NMR、MS和¹³C NMR等方法确证,当反应温度为30 ℃,反应时间为24 h,缩合剂(DCC)与反应物的投料比为1.5:1时,酯键氨解反应的收率最高(65.41%),使得取代喹唑啉酮类化合物的合成路线更加符合工业生产的要求。体外抗真菌活性实验结果表明,所测定的先导化合物对5种临床致病菌都具有潜在的抗真菌活性,值得进一步研究。     

(4S)-1-芴甲氧羰基-4-叠氮基-L-脯氨酸的合成

目的合成用于caspofungin类似物全合成的关键中间体--(4S)-1-芴甲氧羰基-4-叠氮基-L-脯氨酸.方法以(4R)-1-叔丁氧羰基-4-羟基-L-脯氨酸乙酯(2)为原料,经羟基甲磺酰化、叠氮基取代、酯水解、氨基脱叔丁氧羰基保护及9-芴甲氧羰基再保护合成了关键氨基酸中间体(4S)-1-芴甲氧羰基-4-叠氮基-L-脯氨酸,通过质谱(MS)和氢谱(1H-NMR)确证其结构.结果该工艺反应条件温和、操作简便、收率高,总收率达62.3%.     

1,4,5,8-四甲氧基萘-2-甲醛的合成

对紫草素合成中间体1,4,5,8-四甲氧基萘-2-甲醛的制备工艺进行了改进,由萘茜在溴化四丁基铵催化下进行还原甲基化的收率由文献报道的44%提高到90%,标题化合物总收率72%(以对二甲氧基苯计).     

正交设计法优化新型氮唑类抗真菌化合物关键中间体的合成工艺

目的 优化新型氮唑类抗真菌化合物关键中间体的合成工艺。方法 采用正交设计法,重点考察反应温度、投料比、反应时间及溶剂4个因素对收率的影响。结果 反应温度对反应收率的影响最为显著,其次是反应时间;投料比及溶剂对收率影响不明显。结论 新工艺的收率可达50%左右,反应杂质少,后处理简便。     

利拉利汀的合成工艺研究

目的研究利拉利汀的合成工艺。方法以甲基脲为原料,经环合、亚硝化、还原、环合、溴代、取代6步反应得到关键中间体8-溴-7-(2-丁炔基)-3,7-二氢-3-甲基-1H-嘌呤-2,6-二酮(8);再以邻氨基苯乙酮为起始原料,经缩合、环合、还原反应得到中间体2-氯甲基-4-甲基喹唑啉(11);中间体8与中间体11经亲核取代反应得到中间体12,继而与(R)-3-(叔丁氧羰基氨基)哌啶发生取代反应、脱Boc保护基得到目标产物(1),其结构经1H-NM R、M S确证。结果与结论该合成路线,总收率达21.9%(以甲基脲计),原料价廉易得,反应条件温和,后处理简单,为工业化生产奠定了基础。     

由Valiolamine制备伏格列波糖

Valiolamine和1,3-二羟基丙酮在Pd/C作用下催化氢化得到伏格列波糖,收率75%.     

Analysis on improving the conversion rate and waste reduction on bioconversion of Citrullus lanatus seed oil and its characterization

The works focus on maximizing the efficiency and reducing the wastage of reactant to make the possibility of upscaling in the bio-fuel production process for maximum yield conditions. Bio-oil derived from the Citrullus lanatus (Watermelon) for synthesizing methyl ester was used as a feedstock. The value of 1.13 mg KOH/g FFA content is recorded in the oil by employing the titration technique. Henceforth, transesterification using base catalyst reaction was allowed to transform watermelon seed oil into methyl ester. The experimental variables like methanol to oil molar ratio, KOH, and time remained for optimization based on the Taguchi technique. The outcome of the work was a 6:1 M ratio, 1 wt% KOH, 150 min and 55 °C are optimal experimental conditions for maximum conversion efficiency of 93.2%. Amid the four entities, the molar ratio was identified as the substantial influencing variable. The EN14214 standards were compared with characteristics of watermelon methyl ester, and the values obtained have fulfilled the requirements.     

福司氟康唑合成新工艺

目的 优化福司氟康唑合成工艺。方法 以廉价易得氟康唑为起始原料,使用三氯氧磷进行氯磷酸酯化,之后与苄 醇进行缩合,得到中间体 c,将中间体 c 用 Pd/C 催化,以甲酸铵为氢供体,进行脱苄基,经过酸化,析晶,得福司氟康唑。结 果 总收率达 70.7%,纯度为 98.8%,产品结构经 1 H NMR 确证。结论 本文设计了一条新的合成路线,该合成过程操作简单, 起始原料便宜易得,反应条件温和,收率高,易于工业化。     

Hydrierung des 1H-Benzotriazols

Hydrogenation of 1H-Benzotriazole The hydrogenation of 1H-benzotriazole (I) to 4, 5, 6, 7-tetrahydrobenzotriazole (II) with different catalysts as well as the influence of solvents, pressure and temperature was investigated. Great differences in activity exist between Pd, Pt, Rh as black catalysts and the same metals on carriers. Pd/C (10%) was the most suitable catalyst under normal and high pressure. The reaction rates in solvents (CH₃COOH, dioxane, CH₃OH) free of water are increased at the most fifteenfold by addition of 5–10% of water.     

氟哌酸中间体—3-氯-4-氟苯胺亚甲基丙二酸二乙酯的合成工艺改进

3-氯-4-氟苯胺在适当的Lewis酸存在下,与原甲酸三乙酯及丙二酸二乙酯缩合,一步制得了3-氯-4-氟苯胺亚甲基丙二酸二乙酯(Ⅲ),反应收率几乎为100％,本方法可在氟哌酸的生产巾完全代替乙氧_亚甲基丙二酸二乙酯工艺。     

丙酮缩二乙醇液相裂解制备2—乙氧基丙烯

丙酮和原甲酸三乙酯以氯化铵为催化剂反应制得丙酮缩二乙醇,再在硅油中高温裂解制得2－乙氧基丙烯,总收率64．8％。     

Microwave-modified hydrotalcites for the transesterification of soybean oil

The effects of hydrothermal treatment (traditional and microwave-assisted) in the catalytic activity of hydrotalcite were studied in the soybean oil methanolysis for a biofuel production. The catalysts were produced by coprecipitation (pH ≥ 10) and then characterized by x-ray diffraction, infrared spectroscopy, scanning electron microscopy, surface chemical composition, N₂ physisorption at 77 K and surface basicity. Reactions were carried out at 180 °C for 60, 120 and 180 min, molar ratio methanol:soybean oil of 12:1 and 5 wt% of the catalyst. The microwave treatment reduced the aluminum content of catalyst lamellae and increased the surface basicity. The best yield of methyl esters was 95.6% for the catalyst treated by microwave at 110 °C for 300 min. The high yield of methyl esters shows that the use of microwaves in the synthesis of hydrotalcite can reduce the preparation time and increase the industrial competitiveness of this material as a catalyst in the biofuels industry.     

Design and study of ibuprofen disintegrating sustained-release tablets comprising coated pellets.

One challenge in tableting of sustained-release multiparticulates is maintaining the desired drug release after compaction. The aim of this study was to design sustained-release ibuprofen tablets which upon oral ingestion rapidly disintegrate into sustained-release pellets in which the integrity of the pellet core and/or coat is preserved. First free films composed of Eudragit RS 30D and RL 30D in 4:1 ratio and containing different levels of triethyl citrate (TEC) were prepared and tested to optimize the plasticizer level. Cured Eudragit based pellets with 60% ibuprofen loading which in our previous study showed proper mechanical properties for compression were coated with Eudragit RS 30D/RL 30D (4:1) containing 20% triethyl citrate at different coating levels. The mechanical properties of the coated pellets were tested. Polymer coated pellets were compacted into tablets either alone or with a blend of excipients comprising Avicel, PEG 4000, cross-linked PVP. A 3(2) full factorial design was used to optimize the filler blend composition. Effects of pellet to filler ratio, compression force and granulation of filler on tablet characteristics were investigated. Results of mechanical test showed that the coating of cured pellets had no significant effect on yield point and elastic modulus of the pellets. In the case of 5% coating level sustained release of ibuprofen over a period of 24h was achieved. The results obtained from tableting procedure showed that by selecting suitable filler blend (60% Avicel, 10% cross-linked PVP and 30% PEG 4000), compression force, and granulation of filler it was possible to prepare sustained-release tablets containing high ratio of coated pellets (even 80%) with desirable strength, disintegration time, and drug release rate. It was observed that compression force, pellet to filler ratio, composition of filler blend and granulation of fillers had no effect on drug release rate from compacted pellets but had significant influence on tablet strength, friability, and disintegration time. SEM graphs and in vitro release profiles for compacted pellets showed no apparent damage to the coated pellets as a result of the compaction process.     

Solvent-free K–CaO/Ca(OH)2 mixed-phase nanocatalytic single-step methanolysis,ethanolysis and aminolysis of Pongamia pinnata triglycerides

In this report, the K–CaO/Ca(OH)₂ mixed-phase nanodendrites were prepared and used as a heterogeneous catalyst for the one-pot solvent-free synthesis of methyl esters, ethyl esters and alkyl amides from Pongamia pinnata triglycerides. A modified incipient-wetness chemical impregnation method was used to prepared potassium hydroxide doped CaO, MgO, and ZnO nanocrystallites. The prepared K–CaO/Ca(OH)₂ nanocrystallites were found as the most efficient heterogeneous catalyst (4%, w/w) for aminolysis (6:1 M ratio of diethanolamine/oil, 110 °C), methanolysis (9:1 M ratio of methanol/oil at 65 °C) and ethanolysis (9:1 M ratio of ethanol/oil at 75 °C) of Pongamia pinnata oil and took 40 min for the completion (99% yield) of all the reactions. The K–CaO/Ca(OH)₂ nanodendrites were found to be efficient at room temperature (25–30 °C) also and reused for 10 reaction cycles. The pseudo-first-order reaction kinetic model was applied and the first-order rate constant was calculated as 0.112 min^?1, 0.093 min^?1, and 0.118 min^?1 for the methanolysis, ethanolysis, and aminolysis of Pongamia pinnata oil, respectively.