具体实施方式 detailed description

[0026] 下面，结合具体实施方式，对本发明做进一步描述： [0026] Next, with reference to specific embodiments, the present invention is further described:

[0027] -种制备β-阿朴_8'_胡萝卜醛的方法，包括如下步骤： [0027] - kind of preparation of β- apo _8'_ carrot aldehyde, comprising the steps of:

[0028] (1)以2，6，6-三甲基-1-环己烯甲醇和三苯基膦为原料，在浓盐酸或浓硫酸条件下合成为2，6，6-三甲基-1-环己烯甲基三苯基季鱗盐；即在反应瓶中加入甲醇，加入2，6，6-三甲基-1-环己烯甲醇和三苯基膦，2,6,6_三甲基-1-环己烯甲醇和三苯基膦的摩尔比为1: (1-1.5);混合搅拌均匀后，在低于15°C下滴加浓盐酸或浓硫酸，其中，环柠檬醇与浓盐酸或浓硫酸的摩尔比为1:(1-1.5)。 [0028] (1) 2,6,6-trimethyl-1-cyclohexen-methanol as a raw material, and triphenylphosphine, in concentrated hydrochloric acid or concentrated sulfuric acid under conditions for the synthesis of 2,6,6-trimethyl -1-cyclohexene methyltriphenylphosphonium quaternary salt scales; i.e., addition of methanol in a reaction flask was added 2,6,6-trimethyl-1-cyclohexene methanol and triphenylphosphine, 2,6, 6_ molar ratio of trimethyl-1-cyclohexene methanol and triphenylphosphine is 1: (1-1.5); after mixing evenly, at less than 15 ° C was added dropwise concentrated hydrochloric acid or concentrated sulfuric acid, wherein ring or lemon alcohol with concentrated hydrochloric acid concentrated sulfuric acid molar ratio of 1: (1-1.5). 滴加完毕后在氮气保护下加热回流6-10小时。 After the dropwise addition was heated at reflux under nitrogen for 6-10 hours. 待步骤（1)反应完毕后，冷却至室温，加入水，用正己烷萃取两次，水层用二氯甲烷萃取三次，合并有机层，然后用无水Na 2S04干燥，减压除去溶剂，用环己烷或石油醚洗涤除去杂质，或经硅胶柱层析分离得到粘稠状固体，即2,6,6_三甲基-1-环己烯甲基三苯基季鱗盐。 After step (1) completion of the reaction, cooled to room temperature, water was added, extracted twice with n-hexane, and the aqueous layer was extracted three times with dichloromethane, the organic layers combined, dried over anhydrous Na 2S04 and then dried under reduced pressure to remove the solvent, with cyclohexane or petroleum ether to remove impurities, or by silica gel column chromatography to give a viscous solid, i.e. 2,6,6_ trimethyl-1-cyclohexen-methyl triphenyl salt scales.

[0029] (2)将步骤（1)中制得的2,6,6_三甲基-1-环己烯甲基三苯基季鱗盐与2,6，11，15_ 四甲基-2，4，6，8，10，12，14-十六碳七烯二醛经过Wittig反应，即得β-阿朴-8 ' -胡萝卜醛。 [0029] (2) the step (1) obtained in 2,6,6_-trimethyl-1-cyclohexen-methyltriphenylphosphonium salt and quaternary scales 2,6,11,15_ tetramethyl - 2,4,6,8,10,12,14- hexadecene seven ene aldehyde through Wittig reaction, to give the β- apo -8 '- carrot aldehyde. 即将步骤（1)中制得的2，6，6-三甲基-1-环己烯甲基三苯基季鱗盐，在室温条件下搅拌，加入甲醇钠的甲醇溶液，滴加完毕后在氮气保护下搅拌0.5-lh，接着再加入2,6，11，15-四甲基_ 2,4,6,8，10，12，14-十六碳七烯二醛，室温反应1-4小时。 Is about to step (1) obtained in 2,6,6-trimethyl-1-cyclohexen-triphenyl-methyl quaternary salt scales, at room temperature with stirring, was added a solution of sodium methoxide in methanol, after the addition was complete stirred for 0.5-lh under nitrogen, was added followed by _ 2,4,6,8,10,12,14- 2,6,11,15- tetramethyl-hexadecene heptaene dialdehyde room temperature 1- 4 hours. 所述2,6,6-三甲基-1-环己烯甲基三苯基季鱗盐、甲醇钠和2，6，11，15-四甲基-2，4,6,8,10,12,14-十六碳七烯二醛的摩尔比为1: (1-2): (1-1.5)。 The 2,6,6-trimethyl-1-cyclohexen-methyl triphenyl scales salts, sodium methoxide and 2,6,11,15- tetramethyl -2,4,6,8,10 , the molar ratio of 12,14- hexadecene heptaene dialdehyde is 1: (1-2): (1-1.5). 步骤(2)反应后，加饱和氯化铵溶液，CH2C12萃取三次，合并有机层，用无水Na 2S04干燥有机层，减压除去溶剂，经硅胶柱层析或重结晶，得到β-阿朴-8胡萝卜醛。 Step (2) of the reaction, saturated ammonium chloride solution, CH2C12 extracted three times, the organic layers combined, dried over anhydrous Na 2S04 organic layer was dried and the solvent was removed under reduced pressure, purified by silica gel column chromatography or recrystallization, to give β- apo -8 carrot aldehyde. 其中，所述硅胶柱层析中的洗脱系统为石油醚:乙酸乙酯= 10:1。 Wherein, the silica gel column chromatography eluent system of petroleum ether: ethyl acetate = 10: 1.

[0030]本发明的β-阿朴-8 胡萝卜醛的合成路线如下： [0030] β- apo -8 carrot aldehyde synthesis route of the present invention are as follows:

[0032] 所有实施例中，1H-NMR、13C-NMR由Bruker AV-400型核磁共振仪测定，以氘代氯仿(CDC13)为溶剂，四甲基硅烷(TMS)为内标;质谱用Agilent 6210(D0F-MAS)质谱仪测定。 [0032] All examples, 1H-NMR, 13C-NMR by the Bruker AV-400 nuclear magnetic resonance was measured in deuterated chloroform (CDCl3) as solvent and tetramethylsilane (TMS) as internal standard; MS with Agilent 6210 (D0F-MAS) mass spectrometer. [0033]实施例1 β_阿朴_8'_胡萝卜醛的制备： [0033] Example 1 β_ apo ​​_8'_ carrot aldehyde prepared:

[0034] 在100mL反应瓶中加入甲醇（50mL)，2,6,6_三甲基-1-环己稀甲醇（1.54g, lOmmol) 和三苯基膦(3.14g, 12mmol)，混合搅拌均勾后。 [0034] In the reaction flask was added 100mL of methanol (50mL), 2,6,6_ trimethyl-1-cyclohexene methanol (1.54g, lOmmol) and triphenylphosphine (3.14g, 12mmol), mixing after all hook. 在低于15°C下滴加1.5g浓盐酸，滴加完毕后在氮气保护下加热回流8小时。 1.5g of concentrated hydrochloric acid was added dropwise at below 15 ° C, the addition was complete after heating at reflux under nitrogen for 8 hours. TLC(石油醚：乙酸乙酯= 5:1)检测反应终点。 TLC (petroleum ether: ethyl acetate = 5: 1) detecting the end of the reaction. 待反应完毕后却至室温，加入20mL水，用正己烷萃取(25mL X 2)，水层用二氯甲烷萃取(25mL X 3)，合并有机层，无水Na2S04干燥，减压除去溶剂，用环己烷(或石油醚)洗涤除去杂质，或经硅胶柱层析(乙醇)分离得到粘稠状固体，即为2,6,6_三甲基-1-环己烯甲基三苯基季鱗盐，产率50%。 After completion of the reaction was to room temperature, was added 20mL of water, and extracted with n-hexane (25mL X 2), the aqueous layer was extracted with methylene chloride (25mL X 3), the organic layers combined, dried over anhydrous Na2S04, the solvent was removed under reduced pressure, with cyclohexane (or petroleum ether) and dried to remove impurities, or by silica gel column chromatography (ethanol) to give a sticky solid which is 2,6,6_ trimethyl-1-cyclohexene methyltriphenylphosphonium quaternary salt scales, yield 50%. [0035] 在反应瓶中加入2，6，6-三甲基-1 -环己烯甲基三苯基季鱗盐(4.34g，lOmmo 1)和甲醇(20mL)。 [0035] In the reaction flask was added 2,6,6-methyl-1 - cyclohexene methyltriphenylphosphonium scales quaternary salt (4.34g, lOmmo 1) and methanol (20mL). 甲醇钠(0.81 g，15mmo 1)溶于20mL甲醇中，室温搅拌下加入到反应瓶中，滴加完毕后在氮气保护下搅拌〇. 5h，然后再加入2，6，11，15-四甲基-2，4，6，8，10，12，14-十六碳七烯二醛(2.96g，lOmmol)，室温反应4h。 Sodium methoxide (0.81 g, 15mmo 1) was dissolved in 20mL of methanol, stirring at room temperature was added to the reaction flask. After the addition was complete the mixture was stirred under nitrogen billion. 5h, then added tetramethylammonium 2,6,11,15- yl -2,4,6,8,10,12,14- hexadecene heptaene dialdehyde (2.96g, lOmmol), room temperature 4h. 反应完成后加入饱和氯化铵溶液40mL，CH 2C12萃取(25mL X3)，有机层用无水硫酸钠干燥后减压除去溶剂，经硅胶柱层析(石油醚：乙酸乙酯= 10:1) 或重结晶，得到β-阿朴-8 胡萝卜醛，产率38 %。 Saturated ammonium chloride solution was added after the completion of the reaction 40mL, CH 2C12 was extracted (25mL X3), the organic layer was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure, purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10: 1) or recrystallization to give β- apo -8 carrot aldehyde, yield 38%.

[0036] 实施例2 β_阿朴-8'-胡萝卜醛的制备： Preparation Example 2 β_ apo-8'carrot aldehyde [0036] Implementation:

[0037] 在100mL反应瓶中加入甲醇（50mL)，2,6,6_三甲基-1-环己稀甲醇（1.54g, lOmmol) 和三苯基膦(2.62g, lOmmol)，混合搅拌均勾后。 [0037] In the reaction flask was added 100mL of methanol (50mL), 2,6,6_ trimethyl-1-cyclohexene methanol (1.54g, lOmmol) and triphenylphosphine (2.62g, lOmmol), mixing after all hook. 在低于15°C下滴加1.5g浓盐酸，滴加完毕后在氮气保护下加热回流6小时。 1.5g of concentrated hydrochloric acid was added dropwise at below 15 ° C, the addition was complete after heating at reflux under nitrogen for 6 hours. TLC(石油醚：乙酸乙酯= 5:1)检测反应终点。 TLC (petroleum ether: ethyl acetate = 5: 1) detecting the end of the reaction. 待反应完毕后却至室温，加入20mL水，用正己烷萃取(25mL X 2)，水层用二氯甲烷萃取(25mL X 3)，合并有机层，无水Na2S04干燥，减压除去溶剂，用环己烷(或石油醚)洗涤除去杂质，或经硅胶柱层析(乙醇)分离得到粘稠状固体，即为2,6,6_三甲基-1-环己烯甲基三苯基季鱗盐，产率45%。 After completion of the reaction was to room temperature, was added 20mL of water, and extracted with n-hexane (25mL X 2), the aqueous layer was extracted with methylene chloride (25mL X 3), the organic layers combined, dried over anhydrous Na2S04, the solvent was removed under reduced pressure, with cyclohexane (or petroleum ether) and dried to remove impurities, or by silica gel column chromatography (ethanol) to give a sticky solid which is 2,6,6_ trimethyl-1-cyclohexene methyltriphenylphosphonium quaternary salt scales, yield 45%. [0038] 在反应瓶中加入2,6,6_三甲基-1-环己烯甲基三苯基季鱗盐(4.34g，lOmmol)和甲醇(20mL)。 [0038] added 2,6,6_ trimethyl-1-methyl-cyclohexene reaction flask triphenyl scales salt (4.34g, lOmmol) and methanol (20mL). 甲醇钠(0.54g，1 Ommo 1)溶于20mL甲醇中，室温搅拌下加入到反应瓶中，滴加完毕后在氮气保护下搅拌〇. 5h，然后再加入2，6，11，15-四甲基-2，4，6，8，10，12，14-十六碳七烯二醛(2.96g，10mmol)，室温反应lh。 Sodium methoxide (0.54g, 1 Ommo 1) was dissolved in 20mL of methanol, stirring at room temperature was added to the reaction flask. After the addition was complete the mixture was stirred under nitrogen billion. 5h, then add four 2,6,11,15- methyl -2,4,6,8,10,12,14- hexadecene heptaene dialdehyde (2.96g, 10mmol), room temperature lh. 反应完成后加入饱和氯化铵溶液40mL，CH 2Cl2萃取(25mL X3)，有机层用无水硫酸钠干燥后减压除去溶剂，经硅胶柱层析(石油醚：乙酸乙酯= 10:1) 或重结晶，得到β-阿朴-8 胡萝卜醛，产率23 %。 Saturated ammonium chloride solution was added after the completion of the reaction 40mL, CH 2Cl2 was extracted (25mL X3), the organic layer was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure, purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10: 1) or recrystallization to give β- apo -8 carrot aldehyde, yield 23%.

[0039] 实施例3 β_阿朴_8'_胡萝卜醛的制备： Preparation Example 3 β_ apo ​​_8'_ carrot aldehyde [0039] Implementation:

[0040] 在100mL反应瓶中加入甲醇（50mL)，2,6,6_三甲基-1-环己稀甲醇（1.54g, lOmmol) 和三苯基膦(3.85g, 15mmol)，混合搅拌均勾后。 [0040] In the reaction flask was added 100mL of methanol (50mL), 2,6,6_ trimethyl-1-cyclohexene methanol (1.54g, lOmmol) and triphenylphosphine (3.85g, 15mmol), mixing after all hook. 在低于15°C下滴加1.5g浓盐酸，滴加完毕后在氮气保护下加热回流10小时。 1.5g of concentrated hydrochloric acid was added dropwise at below 15 ° C, the addition was complete after heating at reflux under nitrogen for 10 hours. TLC(石油醚：乙酸乙酯= 5:1)检测反应终点。 TLC (petroleum ether: ethyl acetate = 5: 1) detecting the end of the reaction. 待反应完毕后却至室温，加入20mL水，用正己烷萃取(25mL X 2)，水层用二氯甲烷萃取(25mL X 3)，合并有机层，无水Na2S04干燥，减压除去溶剂，用环己烷(或石油醚)洗涤除去杂质，或经硅胶柱层析(乙醇)分离得到粘稠状固体，即为2,6,6_三甲基-1-环己烯甲基三苯基季鱗盐，产率52%。 After completion of the reaction was to room temperature, was added 20mL of water, and extracted with n-hexane (25mL X 2), the aqueous layer was extracted with methylene chloride (25mL X 3), the organic layers combined, dried over anhydrous Na2S04, the solvent was removed under reduced pressure, with cyclohexane (or petroleum ether) and dried to remove impurities, or by silica gel column chromatography (ethanol) to give a sticky solid which is 2,6,6_ trimethyl-1-cyclohexene methyltriphenylphosphonium quaternary salt scales, yield 52%. [0041 ] 在反应瓶中加入2,6,6_三甲基-1-环己烯甲基三苯基季鱗盐(4.34g，lOmmol)和甲醇(20mL)。 [0041] Add 2,6,6_ trimethyl-1-cyclohexen-methyl triphenyl reaction flask scales salt (4.34g, lOmmol) and methanol (20mL). 甲醇钠（1.08g，20mmol)溶于20mL甲醇中，室温搅拌下加入到反应瓶中，滴加完毕后在氮气保护下搅拌〇. 5h，然后再加入2，6，11，15-四甲基-2，4，6，8，10，12，14-十六碳七烯二醛(4.44g，15mmol)，室温反应2h。 Sodium methoxide (1.08g, 20mmol) was dissolved in 20mL of methanol, stirring at room temperature was added to the reaction flask. After the addition was complete the mixture was stirred under nitrogen billion. 5h, then add 2,6,11,15- tetramethyl -2,4,6,8,10,12,14- hexadecene heptaene dialdehyde (4.44g, 15mmol), reaction at room temperature 2h. 反应完成后加入饱和氯化铵溶液40mL，CH 2C12萃取(25mL X3)，有机层用无水硫酸钠干燥后减压除去溶剂，经硅胶柱层析(石油醚：乙酸乙酯= 10:1) 或重结晶，得到β-阿朴-8 胡萝卜醛，产率35 %。 Saturated ammonium chloride solution was added after the completion of the reaction 40mL, CH 2C12 was extracted (25mL X3), the organic layer was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure, purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10: 1) or recrystallization to give β- apo -8 carrot aldehyde, yield 35%.

[0042]取实施例1-3制备得到的β-阿朴_8'_胡萝卜醛进行鉴定，如下为其各种光谱的数据结果： [0042] Preparation Example 1-3 was taken β- apo _8'_ carrot aldehyde implementation were identified as a result of its various spectrum data:

[0043] 产物β_阿朴-8 胡萝卜醛光谱数据： [0043] The product β_ apo ​​-8 carrot aldehyde spectral data:

[0044] 4-^^(4001^,0)(:13):39.45(8,110,6.12-6.96(111,1210,2.06-2.02(111,210,2.00 (s,9H),1.90(s,3H),1.72(s,3H),l.60-1.64(m,2H),l.45-1.49(m,2H),1.03(s,6H)； [0044] 4 - ^^ (4001 ^, 0) (: 13): 39.45 (8,110,6.12-6.96 (111,1210,2.06-2.02 (111,210,2.00 (s, 9H), 1.90 (s, 3H), 1.72 (s, 3H), l.60-1.64 (m, 2H), l.45-1.49 (m, 2H), 1.03 (s, 6H);

[0045] 13C-NMR(100MHz，CDC13)S194.6,149.4,138.7,137.7,136.9,135.2,133.1,131.9, 130.7,129.6,129.1,127.2,126.2,122.7,39.6,34.3,33.2,29.0,21.8,19.3,13.0,12.8, 9·7〇 [0045] 13C-NMR (100MHz, CDC13) S194.6,149.4,138.7,137.7,136.9,135.2,133.1,131.9, 130.7,129.6,129.1,127.2,126.2,122.7,39.6,34.3,33.2,29.0,21.8,19.3 , 13.0,12.8, 9.1 7〇

[0046] HRMS-ESI: Calcd ·For: C3〇H4()0[M+Na] +: 439 · 2977;Found: 439 · 2972。 [0046] HRMS-ESI: Calcd · For: C3〇H4 () 0 [M + Na] +: 439 · 2977; Found: 439 · 2972.

[0047] 对本领域的技术人员来说，可根据以上描述的技术方案以及构思，做出其它各种相应的改变以及形变，而所有的这些改变以及形变都应该属于本发明权利要求的保护范围之内。 [0047] The skilled artisan, according to the technical solutions described above as well as the idea, make the appropriate changes as well as other kinds of deformation, and all of these changes as well as the strain should belong to the scope of the invention as claimed Inside.