芳烃侧链硝酸氧化研究
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摘要
芳烃侧链氧化反应在有机氧化反应中占有重要的地位,其氧化产物及其衍生物是一类重要的精细化工中间体,广泛应用于医药、农药、染料和高分子材料等领域,在国民经济和社会发展中具有重要的价值。
本文提出了一种在中压条件下,用稀硝酸选择性氧化多甲基取代芳烃制备相应苯甲酸的新方法。优化了反应工艺,考察了硝酸浓度、反应温度及反应时间等因素对反应转化率、选择性和产率的影响。研究结果表明：取代基的电子效应和位阻效应是稀硝酸能选择性氧化多甲基取代芳烃的主要原因。芳环上的取代基吸电子能力越弱,其对位甲基反应活性越高,不同取代基对位甲基氧化难易顺序为：-Br>-Cl>-F>-N02；甲基与吸电子取代基的相对位置决定了其被氧化的难易程度,其反应活性顺序为：p-CH3>m-CH3>o-CH3。与文献方法相比,该方法具有操作简单、氧化剂价廉易得、无需昂贵的催化剂、后处理简单、反应时间短、容量性大、转化率高、选择性高和产率较好等优点。
本文采用稀硝酸中压氧化法合成了8个取代芳酸化合物：3-甲基-4-硝基苯甲酸、3-甲基-4-氟苯甲酸、3-甲基-4-溴苯甲酸、3-甲基-4-氯苯甲酸、4-甲基-3-硝基苯甲酸、2-甲基-3-硝基苯甲酸、3,5-二甲基-4-硝基苯甲酸和3,5-二甲基-4-氟苯甲酸。目标产物均经核磁氢谱和核磁碳谱进行了表征,产物的结构均得到了确证。
同时,研究发现：当用硝酸氧化2-氟对二甲苯和2-溴对二甲苯时,结果不甚满意,反应没有选择性。
本文还研究了在中压下,用稀硝酸氧化制备取代芳烃二羧酸。采用这种方法合成了9个取代芳烃二羧酸化合物：4-硝基间苯二甲酸、4-氟间苯二甲酸、4-溴间苯二甲酸、4-氯间苯二甲酸、2-硝基对苯二甲酸、2-氟对苯二甲酸、2-溴对苯二甲酸、3-硝基邻苯二甲酸和4,4’-联苯二甲酸。与文献方法相比,该方法具有产率高、操作简单、原料易得和后处理简单等优点,从而有利于工业化。
Alkylarenes oxidation reactions are of major importance in organic oxidation. The oxidation products and derivatives constitute a particular class in fine chemical intermediates, which have found a large number of uses from medicine, pesticide, dye, polymer materials and so on. It is valuable in the economic and social development.
An efficient and practical method for the selective oxidation of polyalkybenzenes to the corresponding benzoic acid compounds with diluted nitric acid in autoclave has been reported in this thesis.In order to optimize the synthesizing process, the influences of nitric acid concentration, temperature and time on the selectivity and yield have been studied. It was found that the order of oxidation is Br>Cl>F>NO2, when the methyl group is para orientation. The position of the CH3 relative to the electron-withdrawing group also infected the oxidation (para>meta>ortho). Compare to the methods that described in the literatures, this synthetic method is better at simple work-up,without expensive catalyst, simple disposal, short reaction time, high conversion, high selectivity and good yield.
A series of compounds, such as 4-nitro-3-methylbenzoic acid,4-fluoro-3-methyl benzoic acid,4-bromo-3-methyl benzoic acid,4-chloro-3-methylbenzoic acid,3-nitro-4-methylbenzoic acid,3-nitro-2-methylbenzoic acid,4-nitro-3,5-dimethylbenzoic acid and 4-fluoro-3,5-dimethyl benzoic acid have been synthesized with this new method. These compounds were characterized by 1H NMR or/and 13C NMR, respectively.
Unfortunately, the results aren't satisfactory, owing to oxidation reactions of 2-fluoro-p-xylene and 2-bromo-p-xylene give poor selectivity.
In addition, a low-costing method for synthesizing substitute aromatic dicar-boxylic acid has been studied in this paper. This synthetic strategy is superior to that described in the literatures in good yields, simple work-up,easily obtained materials and simple disposal.In that case, this route is easy to commercialize. We have synthesized 4-nitroisophthalic acid,4-fluoroisophthalic acid,4-bromoisophthalic acid, 4-chloroisophthalic acid, Nitroterephthalic acid,2-fluoroterephthalic acid,2-brom-oterephthalic acid,3-Nitrophthalic acid and biphenyl-4,4'-dicarboxylic acid by this novel method.
本文提出了一种在中压条件下,用稀硝酸选择性氧化多甲基取代芳烃制备相应苯甲酸的新方法。优化了反应工艺,考察了硝酸浓度、反应温度及反应时间等因素对反应转化率、选择性和产率的影响。研究结果表明：取代基的电子效应和位阻效应是稀硝酸能选择性氧化多甲基取代芳烃的主要原因。芳环上的取代基吸电子能力越弱,其对位甲基反应活性越高,不同取代基对位甲基氧化难易顺序为：-Br>-Cl>-F>-N02；甲基与吸电子取代基的相对位置决定了其被氧化的难易程度,其反应活性顺序为：p-CH3>m-CH3>o-CH3。与文献方法相比,该方法具有操作简单、氧化剂价廉易得、无需昂贵的催化剂、后处理简单、反应时间短、容量性大、转化率高、选择性高和产率较好等优点。
本文采用稀硝酸中压氧化法合成了8个取代芳酸化合物：3-甲基-4-硝基苯甲酸、3-甲基-4-氟苯甲酸、3-甲基-4-溴苯甲酸、3-甲基-4-氯苯甲酸、4-甲基-3-硝基苯甲酸、2-甲基-3-硝基苯甲酸、3,5-二甲基-4-硝基苯甲酸和3,5-二甲基-4-氟苯甲酸。目标产物均经核磁氢谱和核磁碳谱进行了表征,产物的结构均得到了确证。
同时,研究发现：当用硝酸氧化2-氟对二甲苯和2-溴对二甲苯时,结果不甚满意,反应没有选择性。
本文还研究了在中压下,用稀硝酸氧化制备取代芳烃二羧酸。采用这种方法合成了9个取代芳烃二羧酸化合物：4-硝基间苯二甲酸、4-氟间苯二甲酸、4-溴间苯二甲酸、4-氯间苯二甲酸、2-硝基对苯二甲酸、2-氟对苯二甲酸、2-溴对苯二甲酸、3-硝基邻苯二甲酸和4,4’-联苯二甲酸。与文献方法相比,该方法具有产率高、操作简单、原料易得和后处理简单等优点,从而有利于工业化。
Alkylarenes oxidation reactions are of major importance in organic oxidation. The oxidation products and derivatives constitute a particular class in fine chemical intermediates, which have found a large number of uses from medicine, pesticide, dye, polymer materials and so on. It is valuable in the economic and social development.
An efficient and practical method for the selective oxidation of polyalkybenzenes to the corresponding benzoic acid compounds with diluted nitric acid in autoclave has been reported in this thesis.In order to optimize the synthesizing process, the influences of nitric acid concentration, temperature and time on the selectivity and yield have been studied. It was found that the order of oxidation is Br>Cl>F>NO2, when the methyl group is para orientation. The position of the CH3 relative to the electron-withdrawing group also infected the oxidation (para>meta>ortho). Compare to the methods that described in the literatures, this synthetic method is better at simple work-up,without expensive catalyst, simple disposal, short reaction time, high conversion, high selectivity and good yield.
A series of compounds, such as 4-nitro-3-methylbenzoic acid,4-fluoro-3-methyl benzoic acid,4-bromo-3-methyl benzoic acid,4-chloro-3-methylbenzoic acid,3-nitro-4-methylbenzoic acid,3-nitro-2-methylbenzoic acid,4-nitro-3,5-dimethylbenzoic acid and 4-fluoro-3,5-dimethyl benzoic acid have been synthesized with this new method. These compounds were characterized by 1H NMR or/and 13C NMR, respectively.
Unfortunately, the results aren't satisfactory, owing to oxidation reactions of 2-fluoro-p-xylene and 2-bromo-p-xylene give poor selectivity.
In addition, a low-costing method for synthesizing substitute aromatic dicar-boxylic acid has been studied in this paper. This synthetic strategy is superior to that described in the literatures in good yields, simple work-up,easily obtained materials and simple disposal.In that case, this route is easy to commercialize. We have synthesized 4-nitroisophthalic acid,4-fluoroisophthalic acid,4-bromoisophthalic acid, 4-chloroisophthalic acid, Nitroterephthalic acid,2-fluoroterephthalic acid,2-brom-oterephthalic acid,3-Nitrophthalic acid and biphenyl-4,4'-dicarboxylic acid by this novel method.
引文
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[28]陈洪,黄思庆,等.植物用抗病毒剂的研究—含氟苯甲酸糖酯的合成[J].合成化学,2001,9(4)：337-340.
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[2]Tian H, She X, Shi Y. Electronic probing of ketone cantalyts for asymmetric epoxidat-ion search for more robust catalysts[J].Org. Lett.,2001,3(5):715-718.
[3]Wu X, She X, Shi Y.Highly enantioselective epoxidation of α,β-unsaturated esters by chiral dioxirane[J].J. Am. Chem. Soc.,2002,124(30):8792-8793.
[4]Suresh K, Tardio J, Deepak B,et al. Wet oxidation and catalytic wet oxidation[J].Ind. Eng. Chem. Res.,2006,45(4):1221-1258.
[5]Hindmarsh E, Turner J, Ure A. Process for the production of terephthalic Acid[P]:US, 5563293,1995-06-06.
[6]Alfred S, Bayside N. Preparation of aromatic polycarboxylic acids[P]:US,2833816, 1958-05-06.
[7]Mae K. Composition of synthetic porous crystalline material its synthesis and use[P]: US,4954325,1990.
[8]刘晔,刘蒲,等.微波条件下V2O5/TiO2低温选择氧化甲苯制苯甲酸[J].催化学报,1998,3：224-228.
[9]Hill D, Rudd C,Johnson M. Design and application of a cylindrical mode applicator for the in-line microwave preheating of liquid thermoset[J].J. Microwave. Power. Eletromag. Energ., 1998,23(1):17-20.
[10]Taku N, Noriko A. A biomimetic study of cytochrome P450 related oxidations of tol-uenes using synthetic hemin[J].Bull.Chem. Soc.Jpn.,1996,69(12):3513-3521.
[11]Marcel G, Peter R,Bernard W. TOL plasmid-specified xylene oxygenase is a wide substrate range monooxygenase capable of olefin epoxidation[J].Enzyme.Microb. Tech.1994,16(7):608-615.
[12]王连生.环境化学进展[M].北京：化学工业出版社,1995：378-394.
[13]Yue B,Zhu S,Xie G,et al.Synthesis and characterization of dawson mixedvalence tris(tetrabutylammonium) octadecatungstodiperchlorate[J].Chin. Chem.Lett.,1995,6(3): 215-216.
[14]Attamisio D, Suber L, Thorslund K. Aerobic photooxidation of substituted benzenes catalyzed by the tungsten isopolyanion [W10O32]4[J].Inorg. Chem.,1991,30(3):590-592.
[15]丁正谊.芳烃用Ce(Ⅲ)/Ce(Ⅵ)及Ag(Ⅰ)/Ag(Ⅱ)体系选择性间接电氧化的研究[J].化学试剂,1996,18(4)：243-244.
[16]Falgayrac G, Savall A. Electrochemical activation of the catalytic effect of cobalt in autoxidation of toluene in acetic acid[J].J.Appl.Electrochem.,1999,29:253-255.
[17]Dorin B,Jean L, Gilles F,et al.Electrochemical assistance of catalytic oxidation in li-quid phase using molecular oxygen:oxidation of toluenes[J].Catal. Today,1999,48: 363-369.
[18]Kreh R, Robert M, Joseph L. Selective oxidations with ceric methanesulfonate and ceric trifluoromethanesulfonate[J].Terahedron. Lett.,1987,28(10):1067-1068.
[19]Kreh R, Robert M, Joseph L. Mediated electrochemical synthesis of aromatic aldehy-des ketones and quinones using ceric methanesulfonate[J].J. Org. Chem.,1989,54(7): 1526-1531.
[20]唐陪堃.精细有机合成化学及工艺学[M].天津：天津大学出版社,2002：279-280.
[21]Raghavendrachar P, Ramachandran S.Liquid phase catalytic oxidation of p-xylene[J]. Ind. Eng. Chem. Res.,1992,31(2):453-462.
[22]郭琛.论我国精TA的发展前景与发展思路[J].现代化工,2002,22(10)：1-13.
[23]Lindsay S, Richards D, Thomas C.The role of Vanadium(V) in the oxidation of cyclohexanol to adipic acid by nitric acid[J].J. Chem. Soc. Perkin Trans Ⅱ,1985,10:16-20.
[24]张铸勇,祁国珍.精细有机合成单元反应[M].广州：华南理工大学出版社,2003：307-317.
[25]陈柏洲.对苯二甲醛制备技术进展[J].染料工业,1994,31(2)：25-26.
[26]穆光照.有机活性中间体[M].北京：科学出版社,1988：107-139.
[27]Zaugg H, Rapala R,et al.Organic syntheses. Vol 111.New York:John Wiley and Sons Inc., 1955:820-822.
[28]陈洪,黄思庆,等.植物用抗病毒剂的研究—含氟苯甲酸糖酯的合成[J].合成化学,2001,9(4)：337-340.
[29]Coren L, Cardoni O, Fogari R, et al. A new antogonist for the treatment of essential hypertension[J].Clin. Pharm.Thera.,1996,60:341-343.
[30]Ogiwara T, Azuma J,Watase T, et al.A phase I clinical study of BIBR277 capsules in healthy normal subjects[J].Rinsho. Yakuri.,1995,26:321-324.
[31]Cristopher G, Joseph P, David G. Counterion effects in indium-catalysed aromatic ele-ctrophilic substitution reactions[J].Tetrahedron Lett.,2002,43(27):4789-4791.
[32]Winkler R, Richter M, Kniipfer U, et al. Regio and chemoselective enzymatic N-oxygenation in vivo in vitro and in flow[J].Angew. Chem.Int. Edit.,2006,45(47):8016-8018.
[33]Almog J, Klein A, Sokol A, et al. Urea nitrate and nitrourea:powerful and regiosel-ective aromatic nitration agents[J].Tetrahedron Lett.,2006,47(49):8651-8652.
[34]Gohier F, Castanet A. The first regioselective metalation and functionalization of unprotected 4-halobenzoic Acids[J].J.Org. Chem.,2005,70(4):1501-1504.
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