光学活性紫苏醇的合成及其选择性氧化研究
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摘要
光学活性紫苏醇的合成及其选择性氧化研究是开发我国丰富的松节油资源，利用松节油合成一系列精细化学品的一条重要途径。以松节油中的主要成分β-蒎烯的环氧化合物2，10-环氧蒎烷为原料，经催化重排合成紫苏醇，紫苏醇不仅可作为一种单体香料，还可作为一种重要的有机反应中间体，用来合成一系列更有价值的香料化合物。如紫苏醇选择氧化合成紫苏醛，紫苏醛肟化得到一种高甜度、低热值、味质好、无毒副作用的新型食品添加剂紫苏葶等。
利用β-蒎烯的环氧化合物2，10-环氧蒎烷的开环重排合成紫苏醇是文献报道过的最简易的方法。但该方法在工业生产中存在如紫苏醇产率低、反应过程中原料的聚合量大、产物不易分离等缺点。本文系统研究了2，10-环氧蒎烷液相催化重排的反应规律，对合成紫苏醇的工艺进行了新的探索；同时对紫苏醇在活性MnO_2、CrO_3／SiO_2载体试剂和重铬酸钠三种氧化剂的作用下进一步选择氧化合成紫苏醛进行了探索性研究，获得了一些有应用价值的结果。
1．研究了2，10-环氧蒎烷液相重排的反应规律和产物分布，考察了反应温度、反应时间、溶剂用量、溶剂、溶剂中的含水量等对重排反应的影响。结果表明：在酸催化剂存在下，强极性非质子溶剂中，2，10-环氧蒎烷于353-363 K可定向重排生成紫苏醇。一定条件下反应，2，10-环氧蒎烷的转化率为98.9％，紫苏醇产率为43.8％，原料的聚合量为39.6％；
2．以固定床反应工艺代替传统的搅拌釜式反应，考察了空速、反应温度、溶剂用量对重排反应的影响。结果表明：固定床反应合成紫苏醇在降低2，10-环氧蒎烷聚合量、提高紫苏醇的产率、简化产物分离等方面比传统的间歇搅拌釜式反应器优越。当反应温度为353 K，空速为1.5／h，溶剂用量与2，10-环氧蒎烷体积比为8：1时，2，10-环氧蒎烷的转化率达到91.2％，紫苏醇产率为69.9％，原料的聚合量接近于0；
3.研究了活性MnOZ、Cr03/510:载体氧化试剂和重铬酸钠液相
选择性氧化紫苏醇合成紫苏醛的反应。结果表明:活性MnO:可以选
择性氧化紫苏醇生成紫苏醛，以乙酸乙醋作溶剂，氧化反应温度控
制在328K一溶剂回流温度之间，紫苏醇与氧化剂的质量比为1:4，搅
拌反应4h，紫苏醇转化率可以达到997%，紫苏醛产率达70%以
上;用干混法制备的CrO3/510:载体试剂是紫苏醇液相选择性氧化合
成紫苏醛的高效氧化剂，以二氯甲烷作溶剂，CrO3/510:载体氧化剂
的负载量为2 mmol/g，氧化剂与紫苏醇的摩尔比为2.5:1，室温下搅
拌反应90 min，紫苏醇转化率达到95.0%，紫苏醛产率为57.9%;用
NaZCrZO:作氧化剂，采取边反应边蒸馏的实验工艺，通过三水平三
因素Lg(3，)的正交试验，优化条件下反应，紫苏醛的产率达到
40.0%。
Studies on synthesis and selective oxidation of optical perillyl alcohol are an important procedure to develop abundant turpentine oil of our country and to synthesize a series of fine chemicals. Perillyl alcohol is obtained from rearrangement of 2,10-epoxypinane, which is prepared by epoxidation of 3 -pinene. 3 -pinene is a crucial component of turpentine oil. Perillyl alcohol can be used not only as a kind of flavor but also as an important organic intermediate to produce a series of more important flavors and perfumes. For example, Perillyl aldehyde can be prepared by selective oxidation of perillyl alcohol, and perillatine, obtained from oxidation of perillyl aldehyde, is a sort of new food additive with properties of high sweetness, low caloricity, good flavor and without toxin etc. Synthesis of perillyl alcohol by rearrangement of beta-pinene epoxide is the simplest method reported by literature from 1970 to 2002. But there are some shortcomings in industry production such as low yield of perillyl alcohol, high degree of polymerization, tedious separation of products and so on. In this thesis, rearrangement reaction of 2,10-epoxypinane and selective oxidation of perillyl alcohol are investigated. Some valuable results are obtained as follows:
1. The reaction and the product distribution of liquid isomerization of 2,10-epoxypinane are studied. Effects of reaction conditions on isomerization are investigated. It is discovered that isomerization of 2,10-epoxypinane produce mainly perillyl alcohol in 353 ~ 363 K catalyzed by acid catalysts in strongly polar protonic solvent. Perillyl alcohol can be obtained with 43.8% yield, 98.9% conversion of 2,10-epoxypinane and 39.6% polymerization in optimum condition.
2. Effects of reaction conditions on isomerization in fixed bed are also studied. The results show that synthesis of perillyl alcohol in fixed
bed is better than in stirred reactor in reducing degree of polymerization, improving yield of perillyl alcohol and simplifying separation of products. Perillyl alcohol can be obtained with 69.9% yield, 91.2% conversion of 2,10-epoxypinane and degree of polymerization is near to 0 in the optimum conditions in 353 K, 1.5/h space velocity and the volume ratio of solvent to 2,10-epoxypinane is 8 to 1.
3. Selective oxidation of perillyl alcohol to perillyl aldehyde is studied in the presence of active MnO2, CrO3/SiO2 supported oxidant and Na2Cr2O7. The results show that active MnO2 can be used to oxidize perillyl alcohol to perillyl aldehyde selectively, and conversion of perillyl alcohol is 99.7%, yield of perillyl aldehyde is over 70% in optimum reaction condition with ethyl acetate as solvent, under solvent reflux temperature for 4 h, the mass ratio of oxidant to perillyl alcohol is 4 to 1. CrCVSiO2 supported reagent, prepared by dry mixing method, is an efficient oxidant which oxidize perillyl alcohol to perillyl aldehyde in liquid phase under mild conditions, and conversion of perillyl alcohol is 95.0%, yield of perillyl aldehyde is 57.9% with dichloromethane as solvent under room temperature for 90 min, the ratio of oxidant to perillyl alcohol is 2.5 to 1, loading of CrO3 is 2 mmol/g. The yield of perillyl aldehyde is 40.0% in optimum reaction conditions by 33-orthogonal experiments with the technology of distillation by Na2Cr2O7 oxidant.
利用β-蒎烯的环氧化合物2，10-环氧蒎烷的开环重排合成紫苏醇是文献报道过的最简易的方法。但该方法在工业生产中存在如紫苏醇产率低、反应过程中原料的聚合量大、产物不易分离等缺点。本文系统研究了2，10-环氧蒎烷液相催化重排的反应规律，对合成紫苏醇的工艺进行了新的探索；同时对紫苏醇在活性MnO_2、CrO_3／SiO_2载体试剂和重铬酸钠三种氧化剂的作用下进一步选择氧化合成紫苏醛进行了探索性研究，获得了一些有应用价值的结果。
1．研究了2，10-环氧蒎烷液相重排的反应规律和产物分布，考察了反应温度、反应时间、溶剂用量、溶剂、溶剂中的含水量等对重排反应的影响。结果表明：在酸催化剂存在下，强极性非质子溶剂中，2，10-环氧蒎烷于353-363 K可定向重排生成紫苏醇。一定条件下反应，2，10-环氧蒎烷的转化率为98.9％，紫苏醇产率为43.8％，原料的聚合量为39.6％；
2．以固定床反应工艺代替传统的搅拌釜式反应，考察了空速、反应温度、溶剂用量对重排反应的影响。结果表明：固定床反应合成紫苏醇在降低2，10-环氧蒎烷聚合量、提高紫苏醇的产率、简化产物分离等方面比传统的间歇搅拌釜式反应器优越。当反应温度为353 K，空速为1.5／h，溶剂用量与2，10-环氧蒎烷体积比为8：1时，2，10-环氧蒎烷的转化率达到91.2％，紫苏醇产率为69.9％，原料的聚合量接近于0；
3.研究了活性MnOZ、Cr03/510:载体氧化试剂和重铬酸钠液相
选择性氧化紫苏醇合成紫苏醛的反应。结果表明:活性MnO:可以选
择性氧化紫苏醇生成紫苏醛，以乙酸乙醋作溶剂，氧化反应温度控
制在328K一溶剂回流温度之间，紫苏醇与氧化剂的质量比为1:4，搅
拌反应4h，紫苏醇转化率可以达到997%，紫苏醛产率达70%以
上;用干混法制备的CrO3/510:载体试剂是紫苏醇液相选择性氧化合
成紫苏醛的高效氧化剂，以二氯甲烷作溶剂，CrO3/510:载体氧化剂
的负载量为2 mmol/g，氧化剂与紫苏醇的摩尔比为2.5:1，室温下搅
拌反应90 min，紫苏醇转化率达到95.0%，紫苏醛产率为57.9%;用
NaZCrZO:作氧化剂，采取边反应边蒸馏的实验工艺，通过三水平三
因素Lg(3，)的正交试验，优化条件下反应，紫苏醛的产率达到
40.0%。
Studies on synthesis and selective oxidation of optical perillyl alcohol are an important procedure to develop abundant turpentine oil of our country and to synthesize a series of fine chemicals. Perillyl alcohol is obtained from rearrangement of 2,10-epoxypinane, which is prepared by epoxidation of 3 -pinene. 3 -pinene is a crucial component of turpentine oil. Perillyl alcohol can be used not only as a kind of flavor but also as an important organic intermediate to produce a series of more important flavors and perfumes. For example, Perillyl aldehyde can be prepared by selective oxidation of perillyl alcohol, and perillatine, obtained from oxidation of perillyl aldehyde, is a sort of new food additive with properties of high sweetness, low caloricity, good flavor and without toxin etc. Synthesis of perillyl alcohol by rearrangement of beta-pinene epoxide is the simplest method reported by literature from 1970 to 2002. But there are some shortcomings in industry production such as low yield of perillyl alcohol, high degree of polymerization, tedious separation of products and so on. In this thesis, rearrangement reaction of 2,10-epoxypinane and selective oxidation of perillyl alcohol are investigated. Some valuable results are obtained as follows:
1. The reaction and the product distribution of liquid isomerization of 2,10-epoxypinane are studied. Effects of reaction conditions on isomerization are investigated. It is discovered that isomerization of 2,10-epoxypinane produce mainly perillyl alcohol in 353 ~ 363 K catalyzed by acid catalysts in strongly polar protonic solvent. Perillyl alcohol can be obtained with 43.8% yield, 98.9% conversion of 2,10-epoxypinane and 39.6% polymerization in optimum condition.
2. Effects of reaction conditions on isomerization in fixed bed are also studied. The results show that synthesis of perillyl alcohol in fixed
bed is better than in stirred reactor in reducing degree of polymerization, improving yield of perillyl alcohol and simplifying separation of products. Perillyl alcohol can be obtained with 69.9% yield, 91.2% conversion of 2,10-epoxypinane and degree of polymerization is near to 0 in the optimum conditions in 353 K, 1.5/h space velocity and the volume ratio of solvent to 2,10-epoxypinane is 8 to 1.
3. Selective oxidation of perillyl alcohol to perillyl aldehyde is studied in the presence of active MnO2, CrO3/SiO2 supported oxidant and Na2Cr2O7. The results show that active MnO2 can be used to oxidize perillyl alcohol to perillyl aldehyde selectively, and conversion of perillyl alcohol is 99.7%, yield of perillyl aldehyde is over 70% in optimum reaction condition with ethyl acetate as solvent, under solvent reflux temperature for 4 h, the mass ratio of oxidant to perillyl alcohol is 4 to 1. CrCVSiO2 supported reagent, prepared by dry mixing method, is an efficient oxidant which oxidize perillyl alcohol to perillyl aldehyde in liquid phase under mild conditions, and conversion of perillyl alcohol is 95.0%, yield of perillyl aldehyde is 57.9% with dichloromethane as solvent under room temperature for 90 min, the ratio of oxidant to perillyl alcohol is 2.5 to 1, loading of CrO3 is 2 mmol/g. The yield of perillyl aldehyde is 40.0% in optimum reaction conditions by 33-orthogonal experiments with the technology of distillation by Na2Cr2O7 oxidant.
引文
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81．王央贡，陈家威，杨细香，铬酸／硅胶受载试剂的制备及醇氧化的研究，化学试剂，1985，7(3)：133．
82．陈振初，黄宪，重铬酸季铵盐聚合物试剂的制备及其在醇氧化中的应用，化学试剂，1980，2(5)：24．
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91．丁清杰，蔡琨，选择性氧化的研究-盐酸三甲胺三氧化铬的制备及应用，有机
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70. Dawben W G, Milton Lorber, Fullerton D S, Allylic oxidation of olefins with chromium trioxide-pyridine complex, J. Org. Chem., 1969, 34(11): 3587.
71. Caninell G, Cardillo G, Chromium oxidation in organic chemistry, springer-verlag, Berlin, 1984, 118.
72. W. A. Mosher, D M Preiss, Oxidation of alcohols by electrochemically regen-erated nickel oxide hydroxide. Selective oxidation of hydroxysteroids, J. Am. Chem. Soc., 1953, 75: 5605.
73. J. C Collins, W W Hess, A new, highly selective synthesis of aromatic aldehydes by aerobic free-radical oxidation of benzylic alcohols, catalysed by n-hydroxyphthalimide trader mild conditions. Polar and enthalpic effects, Tetrahedron Lett., 1968, 3(4): 363.
74. Carlsen, Per H. J.; Braenden, Jon Eric, Oxidation of alcohols with potassium chlorochromate, Acta Chem. Stand. Ser. B, 1987, 41(5): 313.
75. E J Corey, G Schmidt, Microwave assisted selective oxidation of benzylic alcohols with calcium hypochlorite under solvent-free conditions, Tetrahedron Lett., 1979, 16(4): 399.
76. Aizpurua J M, Palomo Claudio, Chlorotrimethylsilane/chromium (Ⅵ) reagents as new and versatile oxidation systems, Tetrahedron Lett., 1983, 24(40): 4367.
77. Rathore R, Bhushan Vidya, Chandrasekaran S, Highly selective oxidation of benzylic alcohols with cetyltrimethyl ammonium permanganate, Chem. Lett., 1984,14: 2131.
78. Choudary B M, Durgaprasad A, Valli V L K, Selective oxidation of alcohols by chromia-pillared montmorillonite catalyst, Tetrahedron Lett., 1990, 31 (40): 5785.
79. Hirano Masao, Kuroda Hisanori, Morimoto Takashi, Oxidation of aromatic alcohols with chromium (ⅵ) trioxide in the presence of "wet-aluminium oxide" in aprotic solvent, Bull. Chem. Soc. Japan, 1990, 63(8): 2433.
80. Ji Dong Lou, Chromic acid adsorbed on kieselguhr: a new reagent for the oxidation of primary alcohols to aldehydes, Synth. Commun., 1989, 19(11): 1841.
81．王央贡，陈家威，杨细香，铬酸／硅胶受载试剂的制备及醇氧化的研究，化学试剂，1985，7(3)：133．
82．陈振初，黄宪，重铬酸季铵盐聚合物试剂的制备及其在醇氧化中的应用，化学试剂，1980，2(5)：24．
83. Fillppo J S, Chern C I, Chemisorbed chromyi chloride as a selective oxidant, J. Org. Chem., 1977, 42(12): 2182.
84. Carranza R S, Perez G C, Perez G S, Study of alkyl nitrites oxidation with DMSO, Tetrahedron, 1986, 42(15): 4133.
85. J G Moffatt, Dimethyl sulfoxide (DMSO), a very useful group of procedures for oxidation of alcohols to ketones, J. Org. Chem., 1971, 36: 1909.
86. Shapley Patricia A, Zhang Na Jie, Cerium or ruthenium catalyzed oxidation of alcohols to carbonyl compounds by means of sodium bromate, J. Amer. Chem. Soc., 2000, 122(6): 1079.
87. Yasutaka Ishii, Tatsuya Nakano, Meerwein Ponndorf Verley, Type reduction of ketones and oppenauer type oxidation of alcohols under the influence of Cp_2ZrH_2, J. Org. Chem., 1986, 51: 240.
88. Kazuaki Ishihara, Hideki Kurihara, Hisashi Yamamoto, Bis(pentafluoro-phenyl)borinic acid as a highly effective oppenauer oxidation catalyst for allyic and benzylic alcohols, J. Org. Chem., 1997, 62: 5664.
89. Bessette, Steven M, Quantitation of monoterpenoid compounds with potential medicinal use in biological fluids, PCT Int. Appl., WO 0111026, 1999, 6.
90. Masao Hirano, Toshiyuki Kobayashi, Oxidation of alcohols by silica gel-supported ammonium chlorochromate in solventless system, Synthetic Commu-nications, 1994, 24(13): 1823.
91．丁清杰，蔡琨，选择性氧化的研究-盐酸三甲胺三氧化铬的制备及应用，有机
化学，1988，8：457．
92. Yoshinao Tamaru, Yoshimi Yamada, Kenji Inoue, Oxidation of primary and secondary alcohols by the catalysis of palladium, J. Org. Chem., 1983, 48: 1286.
93．李谦和，尹笃林，张剑峰，β-蒎烯环氧化反应的研究，林产化学与工业，1997，17(2)：19．
94．肖毅，β-蒎烯的环氧化及其催化重排研究，[硕士学位论文]，长沙：湖南师范大学，1999．
95．王建华，化学反应器设计，成都科技大学出版社，1990，235．
96．樊能廷，有机合成事典，北京理工大学出版社(第一版)，1995，60．
97. Khadikar B, Chitnaris A, Khare A, An easy preparation of a silica gel supported chromium trioxide oxidant and its use in the selective oxidation of alcohols, Synth. Commun., 1996, 26(2): 205.
98．张铸勇，祁国珍，庄莆，精细有机合成单元反应，华东理工大学出版社，1998，372．
99．北京师范大学，华中师范大学，南京师范大学 无机化学教研室，无机化学(第三版)，高等教育出版社，1992，861．
100．穆光照，实用溶剂手册(第一版)，上海科学技术出版社，1990，90．
101. Francis A. Carey, Advanced Organic Chemistry (The first edition), 1983, 50.
102. Masao Hirano, Toshiyuki Kobayashi, Takashi Morimoto, A facile preparation of an alumina-supported chromium reagent and its application to the chemoselective oxidation of various alcohols, Synthetic Communications, 1994, 24(13): 1823.
103．伊亨云，朱金明，概率论与数理统计(第一版)，重庆大学出版社，1995，25．