CN114516782A - 一种香紫苏二醇化合物的合成方法 - Google Patents
一种香紫苏二醇化合物的合成方法 Download PDFInfo
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- sclareol
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- XVULBTBTFGYVRC-HHUCQEJWSA-N sclareol Natural products CC1(C)CCC[C@]2(C)[C@@H](CC[C@](O)(C)C=C)[C@](C)(O)CC[C@H]21 XVULBTBTFGYVRC-HHUCQEJWSA-N 0.000 title claims abstract description 47
- XVULBTBTFGYVRC-UHFFFAOYSA-N Episclareol Natural products CC1(C)CCCC2(C)C(CCC(O)(C)C=C)C(C)(O)CCC21 XVULBTBTFGYVRC-UHFFFAOYSA-N 0.000 title claims abstract description 30
- LAEIZWJAQRGPDA-UHFFFAOYSA-N Manoyloxid Natural products CC1(C)CCCC2(C)C3CC=C(C)OC3(C)CCC21 LAEIZWJAQRGPDA-UHFFFAOYSA-N 0.000 title claims abstract description 30
- -1 sclareol compound Chemical class 0.000 title claims abstract description 22
- 238000010189 synthetic method Methods 0.000 title claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 17
- 239000003446 ligand Substances 0.000 claims abstract description 17
- IMKJGXCIJJXALX-UHFFFAOYSA-N ent-Norambreinolide Natural products C1CC2C(C)(C)CCCC2(C)C2C1(C)OC(=O)C2 IMKJGXCIJJXALX-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229940096995 sclareolide Drugs 0.000 claims abstract description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000000654 additive Substances 0.000 claims abstract description 12
- 239000003513 alkali Substances 0.000 claims abstract description 12
- 229910052741 iridium Inorganic materials 0.000 claims abstract description 12
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims abstract description 12
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052698 phosphorus Inorganic materials 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 11
- IMKJGXCIJJXALX-SHUKQUCYSA-N Norambreinolide Chemical compound CC([C@@H]1CC2)(C)CCC[C@]1(C)[C@@H]1[C@]2(C)OC(=O)C1 IMKJGXCIJJXALX-SHUKQUCYSA-N 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 229910052751 metal Inorganic materials 0.000 claims abstract description 8
- 239000002184 metal Substances 0.000 claims abstract description 8
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 230000009471 action Effects 0.000 claims abstract description 4
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 230000000996 additive effect Effects 0.000 claims description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 230000002194 synthesizing effect Effects 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 239000000758 substrate Substances 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 claims description 3
- 239000012429 reaction media Substances 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 3
- 235000011152 sodium sulphate Nutrition 0.000 claims description 3
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 229910000404 tripotassium phosphate Inorganic materials 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 claims description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
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- YPZUZOLGGMJZJO-UHFFFAOYSA-N ambrofix Natural products C1CC2C(C)(C)CCCC2(C)C2C1(C)OCC2 YPZUZOLGGMJZJO-UHFFFAOYSA-N 0.000 description 6
- YPZUZOLGGMJZJO-LQKXBSAESA-N ambroxan Chemical compound CC([C@@H]1CC2)(C)CCC[C@]1(C)[C@@H]1[C@]2(C)OCC1 YPZUZOLGGMJZJO-LQKXBSAESA-N 0.000 description 6
- 150000002596 lactones Chemical class 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000002304 perfume Substances 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
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- 229910010084 LiAlH4 Inorganic materials 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000283222 Physeter catodon Species 0.000 description 2
- BXMJNGVLZAWGJH-UHFFFAOYSA-N [Ir].C1CCC=CC=CC1 Chemical compound [Ir].C1CCC=CC=CC1 BXMJNGVLZAWGJH-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
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- 239000012280 lithium aluminium hydride Substances 0.000 description 2
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
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- 235000005881 Calendula officinalis Nutrition 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
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- 239000002537 cosmetic Substances 0.000 description 1
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- 239000012279 sodium borohydride Substances 0.000 description 1
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- 239000007787 solid Substances 0.000 description 1
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Abstract
本发明提供了一种香紫苏二醇化合物的合成方法，以香紫苏内酯为原料，在由金属铱和二茂铁P,N,N骨架结构类配体组成的催化剂体系作用下发生氢化反应，以高收率得到香紫苏二醇。该催化反应需在叔丁醇钾等碱添加剂的作用下，以异丙醇、甲苯等为溶剂在室温到100摄氏度下进行反应。该反应活性高、反应条件温和，起始原料廉价易得，清洁环保，具有很高的工业应用价值。
Description
技术领域
本发明属于有机合成领域，具体涉及一种香紫苏二醇化合物的铱催化氢化合成方法。
背景技术
龙涎香是一种具有清雅的动物香香气的香料，和麝香、灵猫香、海里香并称为四大动物香料。龙涎香不仅香味持久，而且调和性好，在高档名贵香水中具有很重要的位置[(a)王耀，陶飞燕，周志刚，罗诚，徐恒，合成化学，2018，26(1)55-65；(b)王文军，陈莎，戴乾圜，有机化学，2001，21(3)167-172]。
龙涎香来自于抹香鲸的代谢物，由于抹香鲸濒临灭绝，天然龙涎香越来越少，所以龙涎香的替代品应运而生。目前最能体现龙涎香特征的是降龙涎醚[(c)陆佳庆，潘仙华，欧文华，香料香精化妆品，2008，(1)23-30]。香紫苏醇是唯一实用的合成降龙涎醚的原料[(d)翟周平，农林科技通讯，2002，000(009)，33-33]。香紫苏醇只要经过氧化，还原，环化三个环节就可得到降龙涎醚[(b)]。
香紫苏二醇是合成降龙涎醚的重要中间体，它是由香紫苏醇经过氧化得到内酯，然后再经过还原得到的。因此研究香紫苏二醇的制备对于降龙涎醚的合成具有非常重要的意义。由香紫苏内酯到香紫苏二醇这一步，早期报道的是用LiAlH4，因为其价格昂贵而且操作要求较高，目前用的较多的是NaBH4还原[(e)吴亚，陕西：陕西师范大学，2005.]。但是无论是LiAlH4还是NaBH4相对于直接用氢气还原，价格都要昂贵，而且后处理也麻烦，原子经济性不高。由于环境污染问题越来越突出，国家对环保越来越重视，因此探索新的合成路线，丰富香紫苏二醇的合成方法具有重要的现实意义。
发明内容
本发明的目的是提供一种香紫苏二醇化合物的合成方法，该方法不需要加入大量的碱，操作简单、原料易得、反应活性高，极大的降低了反应成本，具有很高的工业应用价值。
本发明提供了一种香紫苏二醇化合物的合成方法，香紫苏内酯I和氢气为原料，利用金属铱盐和二茂铁P,N,N类配体原位生成铱催化剂，在碱添加剂作用下，发生氢化反应以高收率几乎定量生成香紫苏二醇II。
所述香紫苏内酯化合物具有以下I结构：
所述香紫苏二醇化合物具有以下II结构：
二茂铁P,N,N类配体(L)，其结构通式如下：
其中Ar为苯基及取代苯基，萘基及取代萘基，R为氢、C1-C40烷基、C3-C12环烷基、苯基及取代苯基，所述取代苯基、取代萘基、取代杂环芳香基团的取代基选自C1-C40烷基、C1-C40烷氧基、卤素、硝基、酯基或氰基中的一种或多种，取代基个数为1-5个。
所述碱添加剂选自KOH、NaOH、Na2CO3、Cs2CO3、K2CO3、NaHCO3、iPr2NEt、iPrNMe2、NEt3、tBuOK、、tBuONa、tBuOLi、MeONa、MeOK或K3PO4中的一种或两种以上
反应介质为甲苯、苯、甲醇、乙醇、异丙醇、二氯甲烷、二氯乙烷、四氯化碳、乙酸乙酯、乙醚、四氢呋喃、二甲基亚砜或N,N-二甲基甲酰胺中的至少一种。
所述金属铱选自[Ir(COD)Cl]2、Ir(COD)2BF4或Ir(COD)2BARF的一种。
所述二茂铁P,N,N类配体与金属铱的摩尔比为1-5：1。
所述底物香紫苏内酯化合物和催化剂的摩尔比为100-50000：1。
所述底物香紫苏内酯化合物和碱添加剂的摩尔比为100-10000：1。
在本发明中，所述香紫苏二醇II的制备方法按以下反应路线进行：
具体步骤如下：
在手套箱中，将铱-环辛二烯络合物与二茂铁P,N,N配体溶于溶剂，室温下搅拌30分钟，将其加入到底物香紫苏内酯I的溶剂中，加入碱添加剂，将其置于高压反应釜中，氢气置换3次，然后通入氢气至20-100bar，20-100℃下反应1-24小时，慢慢释放氢气，除去溶剂后加水，然后用乙酸乙酯萃取，硫酸钠干燥，除去溶剂得到香紫苏二醇产品II。
所述的铱-环辛二烯络合物催化剂包括[Ir(COD)Cl]2、Ir(COD)2BF4或Ir(COD)2BARF中一种。优选为[Ir(COD)Cl]2。
反应介质甲苯、苯、甲醇、乙醇、异丙醇、二氯甲烷、二氯乙烷、四氯化碳、乙酸乙酯、乙醚、四氢呋喃、二甲基亚砜或N,N-二甲基甲酰胺中的至少一种。优选为异丙醇。
碱添加剂选自KOH、NaOH、Na2CO3、Cs2CO3、K2CO3、NaHCO3、iPr2NEt、iPrNMe2、NEt3、tBuOK、tBuONa、tBuOLi、MeONa、MeOK或K3PO4中的一种或两种以上。优选为tBuOLi。
所述的二茂铁P,N,N类配体(L)，其结构通式如下：
其中Ar为苯基及取代苯基，萘基及取代萘基；R为氢、C1-C40烷基、C3-C12环烷基、苯基及取代苯基；所述取代苯基、取代萘基的取代基选自C1-C40烷基、C1-C40烷氧基、卤素、硝基、酯基或氰基中的一种或多种，取代基个数为1-5个。
所述配体与铱的摩尔比为1-5：1。
所述底物和催化剂的摩尔比为100-50000：1
所述底物和碱添加剂的摩尔比为100-10000：1
所述的催化反应条件为：
温度：室温-100℃，优选为100℃；
压力：20bar；
时间：0.1-24小时，优选为12小时。
本发明具有以下优点：
1、所用试剂廉价易得。
2、反应活性高、反应条件温和、收率高、选择性好。
3、相比于传统方法，该方法极大的降低了反应成本，简化工艺。
4、配体制备简单，催化剂用量少，整个工艺适合工业化生产。
附图说明
图1为实施例1制备的香紫苏二醇的核磁共振氢谱
图2为实施例1制备的香紫苏二醇的核磁共振碳谱；
具体实施方式
下面的实施例将对本发明予以进一步的说明，但并不因此而限制本发明。核磁共振是通过Bruker400核磁共振仪测定，气相色谱(GC)是通过Agilent 7820色谱测定。
实施例1
L-1的结构式如下：
在手套箱中，将1.3mg[Ir(COD)Cl]2与2.1mg配体L-1溶于2mL甲醇中，室温下搅拌30分钟，将其加入到10g香紫苏内酯中，加入44.8mg叔丁醇钾，30mL甲醇，将其置于高压反应釜中，氢气置换3次，然后通入氢气至20bar，25℃下反应12小时，慢慢释放氢气，除去溶剂后加水，然后用乙酸乙酯萃取，硫酸钠干燥，除去溶剂后得到白色固体。柱层析，然后经NMR测定，得到原料香紫苏内酯4.3g，香紫苏二醇5.2g。然后再经GC分析建立分析方法。核磁数据如下：
1H NMR(400MHz,CDCl3)δ3.80–3.75(m,1H),3.47–3.41(m,1H),1.92-1.87(dt,1H),1.68–1.14(m,14H),0.96-0.96(m,3H),0.79(m,6H).13C NMR(400MHz,CDCl3)δ73.0,64.0,59.3,56.0,44.2,41.9,39.3,39.0,33.4,33.3,27.9,24.6,21.5,20.5,18.4,15.3；
实施例2
L-2的结构式如下：
将实施例1中的配体L-1用配体L-2代替其余同实施例1。GC监测转化率为70％。
实施例3
将实施例1中的碱添加剂叔丁钾用叔丁醇锂代替，其余同实施例1。GC监测转化率为80％。
实施例4
将实施例3中的甲醇用异丙醇代替，其余同实施例3。GC监测转化率为89％。
实施例5
将实施例4中的温度从室温升高到100℃，其余同实施例4。GC监测内酯完全转化。处理后柱层析得到产品10g，收率99％。
实施例6
将实施例5中称取的金属铱和配体的质量都减半，其余同实施例5。GC监测内酯完全转化。处理后柱层析得到产品10g，收率99％。
实施例7
将实施例6中称取的碱量减为十分之一，其余同实施例6。GC监测内酯完全转化。处理后柱层析得到产品10g，收率99％。
以上所述实施案例仅表达本发明的实施方式，但并不能因此而理解为对本发明专利的范围的限制，应当指出，对于本领域的技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些均属于本发明的保护范围。
Claims (9)
1.一种香紫苏二醇化合物的合成方法，其特征在于：以香紫苏内酯化合物和氢气为原料在由金属铱和二茂铁P,N,N类配体组成的催化剂体系和碱添加剂的作用下，发生氢化反应生成香紫苏二醇。
2.按照权利要求1所述香紫苏二醇的合成方法，其特征在于：所述香紫苏内酯化合物具有以下I结构：
3.按照权利要求1所述香紫苏二醇的合成方法，其特征在于：所述香紫苏二醇化合物具有以下II结构：
4.按照权利要求1所述香紫苏二醇的合成方法，其特征在于：二茂铁P,N,N类配体(L)，其结构通式如下：
其中Ar为苯基及取代苯基，萘基及取代萘基，R为氢、C1-C40烷基、C3-C12环烷基、苯基及取代苯基，所述取代苯基、取代萘基、取代杂环芳香基团的取代基选自C1-C40烷基、C1-C40烷氧基、卤素、硝基、酯基或氰基中的一种或多种，取代基个数为1-5个。
5.按照权利要求1所述的香紫苏二醇化合物的合成方法，其特征在于：所述金属铱选自[Ir(COD)Cl]2、Ir(COD)2BF4或Ir(COD)2BARF的一种。
6.按照权利要求1所述的香紫苏二醇化合物的合成方法，其特征在于：所述二茂铁P,N,N类配体与金属铱的摩尔比为1-5：1。
7.按照权利要求1所述的香紫苏二醇化合物的合成方法，其特征在于：所述底物香紫苏内酯化合物和催化剂的摩尔比为100-50000：1。
8.按照权利要求1所述的香紫苏二醇化合物的合成方法，其特征在于：所述底物香紫苏内酯化合物和碱添加剂的摩尔比为100-10000：1。
9.根据权利要求1所述的香紫苏二醇化合物合成方法，其特征在于：该方法具体为：
在手套箱中，将金属铱与二茂铁P,N,N配体溶于溶剂，室温下搅拌30分钟，将其加入到底物香紫苏内酯的溶剂中，加入碱添加剂，将其置于高压反应釜中，氢气置换3次，然后通入氢气至20-100bar，20-100℃下反应1-24小时，慢慢释放氢气，除去溶剂后加水，然后用乙酸乙酯萃取，硫酸钠干燥，除去溶剂得到产品；
碱添加剂选自KOH、NaOH、Na2CO3、Cs2CO3、K2CO3、NaHCO3、iPr2NEt、iPrNMe2、NEt3、tBuOK、、tBuONa、tBuOLi、MeONa、MeOK或K3PO4中的一种或两种以上；
反应介质为甲苯、苯、甲醇、乙醇、异丙醇、二氯甲烷、二氯乙烷、四氯化碳、乙酸乙酯、乙醚、四氢呋喃、二甲基亚砜或N,N-二甲基甲酰胺中的至少一种。
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1768944A (zh) * | 2004-11-01 | 2006-05-10 | 中国科学院大连化学物理研究所 | 一种以膦－亚磷酰胺酯为配体的催化剂及制法和应用 |
| CN106414375A (zh) * | 2014-01-24 | 2017-02-15 | 奇华顿股份有限公司 | 化合物中或与之相关的改进 |
| WO2019138000A1 (en) * | 2018-01-10 | 2019-07-18 | Basf Se | Use of a ruthenium catalyst comprising a tetradentate ligand for hydrogenation of esters and/or formation of esters and a ruthenium complex comprising said tetradentate ligand |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1768944A (zh) * | 2004-11-01 | 2006-05-10 | 中国科学院大连化学物理研究所 | 一种以膦－亚磷酰胺酯为配体的催化剂及制法和应用 |
| CN106414375A (zh) * | 2014-01-24 | 2017-02-15 | 奇华顿股份有限公司 | 化合物中或与之相关的改进 |
| WO2019138000A1 (en) * | 2018-01-10 | 2019-07-18 | Basf Se | Use of a ruthenium catalyst comprising a tetradentate ligand for hydrogenation of esters and/or formation of esters and a ruthenium complex comprising said tetradentate ligand |
Non-Patent Citations (1)
| Title |
|---|
| "MANGANESE CATALYZED HYDROGENATION OF ENANTIOMERICALLY PURE ESTERS": ""Manganese Catalyzed Hydrogenation of Enantiomerically Pure Esters"", 《ORGANIC LETTERS》, vol. 20, pages 2654 - 2658, XP055574003, DOI: 10.1021/acs.orglett.8b00864 * |
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