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Goal compound synthesis namely: Take the vanillic acid as outset raw material, obtains 4- hydroxyl - 3- anisole methyl formate with the methyl alcohol reflux conditions, then after the etherification, the nitration, the return to original state, the ring closure response obtains 6- methoxy - 7- animal pen oxygen radical kui zuo lin - 4- alkone, then passes through the chlorination, the substitution aniline, to escape responses again and so on animal pen oxygen radical, etherification to obtain the goal compound; The goal compound and the diethylamine had the amine substitution reaction to obtain TM1, namely 4- benzene amino - 6- methoxy - 7- [2- hydroxyl - 3-(N, N- two ethyl aminos) third oxygen radical] kui zuo lin; Through zuo has the etherification with the Austria niter to respond obtains TM2, namely 4- benzene amino - 6- methoxy - 7- [2- hydroxyl - 3-(2- methyl - 5- nitryl imidazole) third oxygen radical] kui zuo lin.

目标化合物的合成即:以香草酸为起始原料,与甲醇回流条件下得到4-羟基-3-甲氧基苯甲酸甲酯,然后经过醚化、硝化、还原、环合反应得到6-甲氧基-7-苄氧基喹唑啉-4-酮,然后再经氯化、取代苯胺、脱苄氧基、醚化等反应得到目标化合物;目标化合物与二乙胺发生胺取代反应得到了TM1,即4-苯氨基-6-甲氧基-7-[2-羟基-3-丙氧基]喹唑啉;通过与奥硝唑发生醚化反应得到TM2,即4-苯氨基-6-甲氧基-7-[2-羟基-3-(2-甲基-5-硝基咪唑)丙氧基]喹唑啉。

The other for: safrole, sassafras oil, safrole different 82 yuan / kg; 1 - phenyl -2 - propanone 2,500 yuan / kg; 3.4 dioxane methylene diphenyl -2 - propanone 7200 yuan / ton; Piperonal 1,000 yuan / kg; N-acetyl-o-amino benzoic acid 11500 yuan / ton; anthranilic acid 15,500 yuan / ton; Phenylacetate 15,000 yuan / ton; acetic anhydride 9900 yuan / ton; trichloromethane 4100 yuan / ton ; anhydrous ether 8500 yuan / ton; piperidine 58000 yuan / ton; methyl ethyl ketone 10,000 won / ton; sulfate 1,200 yuan / ton; hydrochloride 400 yuan / ton; ethanol 4200 yuan / ton.

另供:黄樟素、黄樟油、异黄樟素82元/公斤;1-苯基-2-丙酮2500元/公斤;3.4 亚甲基二氧苯基-2-丙酮7200元/吨;胡椒醛1000元/公斤;N-乙酰邻氨基苯酸11500元/吨;邻氨基苯甲酸15500元/吨;苯乙酸15000元/吨;醋酸酐9900元/吨;三氯甲烷4100元/吨;无水乙醚8500元/吨;哌啶58000元/吨;甲基乙基酮10000元/吨;硫酸1200元/吨;盐酸400元/吨;无水乙醇4200元/吨。

The other for: safrole, sassafras oil, safrole different 82 yuan / kg; 1 - phenyl -2 - propanone 2,500 yuan / kg; 3.4 dioxane methylene diphenyl -2 - propanone 7200 yuan / ton; Piperonal 1,000 yuan / kg; N-acetyl-o-amino benzoic acid 11500 yuan / ton; anthranilic acid 15,500 yuan / ton; Phenylacetate 15,000 yuan / ton; acetic anhydride 9900 yuan / ton; trichloromethane 4100 yuan / ton ; anhydrous ether 8500 yuan / ton; piperidine 58000 yuan / ton; toluene 5200 yuan / ton; methyl ethyl ketone 10,000 won / ton; sulfate 1,200 yuan / ton; hydrochloride 400 yuan / ton; anhydrous Ethanol 4200 yuan / ton.

另供:黄樟素、黄樟油、异黄樟素82元/公斤;1-苯基-2-丙酮2500元/公斤;3.4 亚甲基二氧苯基-2-丙酮7200元/吨;胡椒醛1000元/公斤;N-乙酰邻氨基苯酸11500元/吨;邻氨基苯甲酸15500元/吨;苯乙酸15000元/吨;醋酸酐9900元/吨;三氯甲烷4100元/吨;无水乙醚8500元/吨;哌啶58000元/吨;甲苯5200元/吨;甲基乙基酮10000元/吨;硫酸1200元/吨;盐酸400元/吨;无水乙醇4200元/吨。

Synthesis of target compounds namely: to vanillic acid as the starting material with methanol under reflux conditions for 4 - hydroxy -3 - p-methyl, then ether, and nitration, reduction, cyclization reaction 6 - methoxy -7 - benzyloxy-quinazoline -4 - one, and then by the chloride in place of aniline, benzyloxy-off, such as etherification reaction of the target compounds; target compounds with the second and third occurrence of substitution reactions of amines by the TM1, that is, 4 - amino-benzene -6 - methoxy -7 - [2 - hydroxy -3 -(N, N-diethyl amino) oxy c] quinazoline; with ether occurred Ornidazole reaction of TM2, namely, 4 - amino-benzene -6 - methoxy -7 - [2 - hydroxy -3 -(2 - methyl -5 - nitroimidazole) C oxy] quinazoline.

本论文以嘌呤类似物喹唑啉为母核,分别在其4位和7位引入结构多样的取代苯氨基和柔性侧链,设计了一系列4-取代苯胺基-6-甲氧基-7-(2-羟基取代丙氧基)喹唑啉类化合物。目标化合物的合成即:以香草酸为起始原料,与甲醇回流条件下得到4-羟基-3-甲氧基苯甲酸甲酯,然后经过醚化、硝化、还原、环合反应得到6-甲氧基-7-苄氧基喹唑啉-4-酮,然后再经氯化、取代苯胺、脱苄氧基、醚化等反应得到目标化合物;目标化合物与二乙胺发生胺取代反应得到了TM1,即4-苯氨基-6-甲氧基-7-[2-羟基-3-丙氧基]喹唑啉;通过与奥硝唑发生醚化反应得到TM2,即4-苯氨基-6-甲氧基-7-[2-羟基-3-(2-甲基-5-硝基咪唑)丙氧基]喹唑啉。

The condensation of 3 carbethoxy isoquinol 4 one with carbamidine, amidine, carbamide and sulfocarbamide gave isoquinolo pyrimidine derivatives, respectively and isoquinolo quinoline derivatives were synthesized by the reaction of o aminobenzaldehyde or o aminopiperonal with isoquinol 4 one.

报道了利用 3 乙氧甲酰基异喹啉 4 酮分别与胍、脒、脲及硫脲类化合物缩合反应合成异喹啉并嘧啶衍生物,邻氨基苯甲醛、邻氨基胡椒醛分别与异喹啉 4 酮反应合成异喹啉并喹啉化合物。6个新化合物的结构通过元素分析、红外光谱、核磁共振氢谱和质谱予以证

The same year with the Institute of Fine Chemicalto develop fine chemical products - o-aminobenzoic acid, and 1.4 million yuan of funds into an annual output of 200 tons built anthranilic acid production line, by the province for the Prohibition of Chemical Weapons Convention to fulfill the work of leadership Office approval in April 2002 with an annual output of 200 tons of the scale of operation, product quality compared with similar products in the domestic leading level, in October 2002 to carry out technical transformation again, the scale of production from 200 tons; years expanded to 500 tons; in size, and product performance, production capacity of plant expansion requirements, in 2003 officially put into operation. The end of 2004 our company moved to Sequoia small city are on the 1st, covering over 20,000 square meters, anthranilic acid after the removal of the production line expanded to 1200 tons; in size, at the same time developed a 2,2 - Dithio Benzophenone acid, benzo-iso thiazoline -3 - one, dichloro-acetonitrile, thiophene tons of ketones, a series of inter-amino benzoic acid, etc. Fine Chemical Products.

同年公司与上海桑迪精细化工研究所合作开发精细化工产品—邻氨基苯甲酸,并投入140万元资金建成了年产200吨邻氨基苯甲酸生产线,经省履行禁止化学武器公约工作领导小组办公室批准于2002年4月以年产200吨的规模投入运行,产品质量与国内同类产品相比处于领先水平,2002年10月公司再次进行技改,把生产规模由原来的200吨;年扩到500吨;年规模,且产品性能、生产装置能力达到扩产的要求,2003年正式投入运行。2004年末我公司搬迁至杉城小均1号,占地2万多平方米,搬迁后邻氨基苯甲酸生产线扩大到1200吨;年规模,同时开发了2,2-二硫代二苯甲酸、苯并异噻唑啉-3-酮、二氯乙腈、噻吨酮、间氨基苯甲酸等一系列化工精细产品。

Aniline compounds are used as raw material and reacted with anthranilic acid and then phenyl iodide as alkylating agents to give alkylating products followed by cyclizing with concentrated sulphuric acid to give a N-phenyl-acridone(or 3-ethoxyl-N-phenylacridone).The structure of intermediate and target compound are determined by IR and MS.

以苯胺类化合物为原料,先后以邻氯苯甲酸和碘苯为烷基化试剂进行了N 烷基化反应,再用浓硫酸使其环化制得N-苯基吖啶酮和3-乙氧基-N-苯基吖啶酮,并用红外光谱及质谱仪检测了各中间体及目标产物的结构。

Based on the synthesis method and the function of decreasing blood glucose levels of rosiglitazone, and the report on benzoquinones which resulted in a significant decrease in blood glucose levels, a novel non-thiazolidinedione class of PPARy agonist 2, 5-Dihydroxy-3-{4-[2-(methyl- pyridin-2- yl-amino)- ethoxy] -phenyl}-6-phenyl-[l, 4] benzoquinone (4) was designed and synthesized.

在合成罗格列酮的基础上,根据某些醌类结构化合物的类似胰岛素作用,设计并合成了一种非噻唑烷二酮类PPARγ激动剂2,5-二羟基3-{4-[2-(甲基-2-吡啶氨基)-乙氧基]-苯基}-6-苯基-1,4苯醌(4)。

In this thesis,the AM1,MNDO,MINDO/3(mainly AM1)and INDO/S-CI semiempirical MO methods were used toinvestigate the excited-state intramolecular protontransfer reactions of salicylic acid derivatives—salicylic acid,methyl salicylate,salicylaldehyde,o-hydroxyaceto-phenone,salicylamide and 3-hydroxy-picolinamide (6 conformers and 2-3 anion species);2-(2'-hydroxy-5' methylphenyl) benzotriazole(4 conformers),2-(2' hydroxyphenyl) benzimidazole (3 conformers and 3anion species),Bis-2,5-(2-benzoxazolyl)hydroquinone(3 conformers),2-(2'-hydroxyphenyl)benzothiazole(2conformers) and 7-azaindole dimer (2 conformers).Theinvestigations were described as follows.Geometry optimization,relative stability andhydrogen bonding energy First,for sylicylic acid derivative molecules,the AM1,MNDO and MINDO/3 methods were used toinvestigate ground-state geometry optimization,energies,relative stabilities and hydrogen-bondingenergies on the five kinds of the molecules(designing 6 conformers and 2-3 anion species).Comparing with experimental data,the optimizedgeometry,the order of stability,the hydrogen-bonding energies and the distances between O-O in O-H..O hydrogen bonds by AM1 method were in agreementwith the experimental data,however,the C-C bondlengths optimized by MNDO and MINDO/3 were longer,C-O and O-H bond lengths were shorter;for C-N bondlengths,the results opitimized by MNDO method werethe same as those by AM1 method,nevertheless the C-Nbond lengths given by MINDO/3 method were muchshorter.For some sylicylic acid derivatives(e.g.methyl salicylate,salicylamide),the order ofstabilities on the conformers given by MNDO andMINDO/3 methods were not in agreement with theexisting conformers deduced by experimental methods,and the hydrogen bonding energies calculated by MNDO.and MINDO/3 methods were smaller.Second,the studyon the other systems found that the optimizedgeometry of the proton-transfered product with INDOmethod could not be obtained,only could theoptimized geometry of reactant be obtained,and thecalculated hydrogen bonding energies were greater.Many results of calculation indicated that the studyon the excited-state intramolecular proton transferreaction system using AM1 method was suitable andreliable.

本论文用AM1、MNDO、MINDO/3(主要是AM1)和INDO/S-CI半经验分子轨道方法对水杨酸衍生物系列——水杨酸、水杨酸甲酯、水杨醛、O-羟基乙酰苯酮、水杨酰胺和3-羟基吡啶酰胺(6种异构体和2-3种阴离子);2-(2'-羟基-5'-甲基苯基)苯并三〓唑(4种异构体);2-(2'-羟基苯基)苯并咪唑(3种异构体和3种阴离子);2,5-二间氮杂氧茚氢醌(3种异构体);2-(2'-羟基苯基)间〓杂硫茚(2种异构体)和7-〓吲哚二体(2种异构体)的激发态分子内质子转移反应在以下几个方面进行了较系统的理论研究:几何构型优化和相对稳定性及氢键能首先以水杨酸衍生物系列分子为例,用AM1、MNDO和MINDO/3方法考察了5种分子(每种分子设计6种异构体和2-3种阴离子)的基态几何构型优化,能量、相对稳定性和氢键能计算,通过和实验数据进行比较,AM1方法给出的优化几何构型、稳定性次序、氢键能和O—H。。。O氢键的0—0距离与实验数据吻合最好,MNDO和MINDO/3方法优化的C-C键长偏长,C-O键和O-H键长偏短;对于C-N键长,MNDO和AM1优化结果差别不大,而MINDO/3给出了过短的C-N键长,MNDO和MINDO/3方法给出的有些水杨酸衍生物分子(如水杨酸甲酯和水杨酰胺)异构体的稳定性次序和实验上推测的可存在异构体结果不一致,MNDO和MINDO/3方法给出的氢键能偏低,对其他体系的研究发现INDO方法常常不能得到质子转移产物的优化几何构型,只能得到反应物的优化构型,并且估算的氢键能偏高,大量的计算结果表明AM1方法对本论文研究的激发态分子内质子转移反应体系是适宜和可靠的。

Their chemical structures were characterizd on the basis of spectral and chemical evidences to be: Sarracenin (1), 2-methyl-5-hydroxy-7-O-ethyl caffeate chromome (2), Naringenin(3), 2-methyl-5, 7-dihydroxychromome (4), 2-methyl-6-hydroxyl-cinnamic acid methyl ester (5), eriodictyol (6), quercetin (7), Naringenin-7-O-β-D-glucoside( 8 ), eriodictyol-7-O-α-D-glucoside (9), quercetin-3-O-β-D-glucoside(10). In addition, one compound was abtained from the n-butanol frationk, which was finally identified as Morrosiside(11) by spectral and chemical evidences.

以波谱数据及其理化性质鉴定为:Sarracenin(1),2-甲基-5-羟基-7-O-咖啡酸乙酯色原酮(2),柚皮素(3),2-甲基-5,7-二羟基色原酮(4),2-甲基-6-羟基苯丙烯酸甲酯(5),圣草酚(6),槲皮素(7),柚皮素-7-O-β-D-葡萄糖苷(Naringenin-7-O-β-D-glucoside)(8),圣草酚-7-O-α-D-葡萄糖苷(eriodictyol-7-O-α-D-glucoside)(9),槲皮素-3-O-β-D-葡萄糖苷(quercetin--3-O-β-D-glucoside)(10);另外从正丁醇萃取部位分离得到1个化合物,以波谱数据和文献对照鉴定为:Morroniside(11)。

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