Preparation method of quinone compound

文档序号：1915871 发布日期：2021-12-03 浏览：23次中文

阅读说明：本技术 一种醌类化合物的制备方法 (Preparation method of quinone compound ) 是由李智张子宁于 2020-05-28 设计创作，主要内容包括：本发明公开了一种醌类化合物的制备方法。本发明提供了一种醌类化合物的制备方法,其包括下述步骤：在碱的存在下,将如式II所示的化合物和如式III所示的化合物进行缩合反应,得到如式I所示的醌类化合物即可；所述的碱的碱性强于苯酚钠。该方法操作简单,适于工业化生产。(The invention discloses a preparation method of quinone compounds. The invention provides a preparation method of quinone compounds, which comprises the following steps: in the presence of alkali, carrying out condensation reaction on a compound shown as a formula II and a compound shown as a formula III to obtain a quinone compound shown as a formula I; the alkali is more basic than sodium phenolate. The method is simple to operate and suitable for industrial production.)

1. A preparation method of a quinone compound shown in a formula I comprises the following steps: in the presence of alkali, carrying out condensation reaction on a compound shown as a formula II and a compound shown as a formula III to obtain a quinone compound shown as a formula I; the alkalinity of the alkali is stronger than that of sodium phenolate;

wherein R is¹Is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

R²is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

R³is hydrogen,C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

or, R²、R³And the carbon atoms to which they are attached form C₆～C₁₀Aryl of (a), C substituted by one or more hydroxy groups₆～C₁₀Aryl of (a), or 5-to 10-membered heteroaryl; the hetero atom in the heteroaryl is selected from one or more of N, O and S, and the number of the hetero atoms is 1,2 or 3;

R⁴is O;

R⁵is O;

R⁶is C₃～C₁₀₀By one or more R^6-1Substituted C₃～C₁₀₀Or, C₃～C₁₀Cycloalkenyl group of (a);

R^6-1independently is C₆～C₁₀Aryl of (a), or 5-to 10-membered heteroaryl; the hetero atom in the heteroaryl is selected from one or more of N, O and S, and the number of the hetero atoms is 1,2 or 3;

x is halogen.

2. The method of claim 1, wherein R is represented by formula I¹Is hydrogen, C₁～C₁₀Alkyl or C₁～C₁₀Alkoxy group of (a);

and/or, R²Is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a); r³Is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a); or, R²、R³And the carbon atoms to which they are attached form C₆～C₁₀Aryl of (a), or C substituted by one or more hydroxy groups₆～C₁₀Aryl of (a);

and/or, R⁶Is C₃～C₁₀₀Alkenyl groups of (a).

3. The method of claim 2, wherein R is represented by formula I²Is hydrogen, C₁～C₁₀Alkyl or C₁～C₁₀Alkoxy group of (a); r³Is hydrogen, C₁～C₁₀Alkyl or C₁～C₁₀Alkoxy group of (a); or, R²、R³And the carbon atoms to which they are attached form C₆～C₁₀Aryl of (a), or C substituted by one or more hydroxy groups₆～C₁₀Aryl group of (1).

4. The process for preparing a quinone compound of formula I as claimed in claim 3, wherein R is²Is hydrogen, C₁～C₄Alkyl or C₁～C₄Alkoxy group of (a); r³Is hydrogen, C₁～C₄Alkyl or C₁～C₄Alkoxy group of (a); or, R²、R³And the carbon atoms to which they are attached together form a phenyl group, or a phenyl group substituted with one or more hydroxyl groups.

5. The process for the preparation of a quinone compound of formula I according to claim 1, wherein each group is defined as in any one of the following schemes:

scheme 1:

R¹is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

R²is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

R³is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

alternatively, the first and second electrodes may be,R²、R³and the carbon atoms to which they are attached form C₆～C₁₀Aryl of (a), or C substituted by one or more hydroxy groups₆～C₁₀Aryl of (a);

R⁴is O;

R⁵is O;

R⁶is C₃～C₁₀₀By one or more R^6-1Substituted C₃～C₁₀₀Or, C₃～C₁₀Cycloalkenyl group of (a);

R^6-1independently is C₆～C₁₀Aryl of (a);

x is halogen;

scheme 2:

R¹is hydrogen, C₁～C₁₀Alkyl or C₁～C₁₀Alkoxy group of (a);

R²is hydrogen, C₁～C₁₀Alkyl or C₁～C₁₀Alkoxy group of (a);

R³is hydrogen, C₁～C₁₀Alkyl or C₁～C₁₀Alkoxy group of (a);

or, R²、R³And the carbon atoms to which they are attached form C₆～C₁₀Aryl of (a), or C substituted by one or more hydroxy groups₆～C₁₀Aryl of (a);

R⁴is O;

R⁵is O;

R⁶is C₃～C₁₀₀Alkenyl of (a);

x is halogen;

scheme 3:

R¹is hydrogen, C₁～C₄Alkyl or C₁～C₄Alkoxy group of (a);

R²is hydrogen, C₁～C₄Alkyl or C₁～C₄Alkoxy group of (a);

R³is hydrogen, C₁～C₄Alkyl or C₁～C₄Alkoxy group of (a);

or, R²、R³And the carbon atoms to which they are attached together form a phenyl group, or a phenyl group substituted with one or more hydroxyl groups;

R⁴is O;

R⁵is O;

R⁶is phytyl orn is 0 to 9;

x is halogen.

6. The process for the preparation of a quinone compound of formula I according to claim 1, wherein each group is defined as in any one of the following schemes:

scheme a:

the compound shown in the formula II is 1, 4-benzoquinone, 2-methyl-1, 4-benzoquinone, 2, 3-dimethyl-1, 4-benzoquinone, 2,3, 5-trimethyl-1, 4-benzoquinone, 2, 3-dimethoxy-5-methyl-1, 4-benzoquinone, 2-methyl-1, 4-naphthoquinone and 5-hydroxy-1, 4-naphthoquinone;

R⁶is 3-methyl-2-buten-1-yl, (all-E) -3, 7-dimethyl-2, 6-octadien-1-yl, (all-E) -3,7, 11-trimethyl-2, 6, 10-dodecatrien-1-yl, phytyl, (all-E) -3,7,11, 15-tetramethyl-2, 6,10, 14-hexadecatetraen-1-yl, (all-E) -3,7,11,15,19,23, 27-heptamethyl-2, 6,10,14,18,22, 26-dioctadecylheptaen-1-yl, (all-E) -3,7,11,15,19,23,27,31, 35-nonamethyl-2, 6,10,14,18,22,26,30, 34-trihexadecanonaen-1-yl or (all-E) -3,7,11,15,19,23,27,31,35, 39-decamethyl-2, 6,10,14,18,22,26,30,34, 38-forty decaen-1-yl;

scheme b:

the compound shown in the formula II is 2, 3-dimethoxy-5-methyl-1, 4-benzoquinone; r⁶Is composed ofn is 0,1, 2,3, 4, 5, 6, 7, 8 or 9;

scheme c:

the compound shown in the formula II is 2-methyl-1, 4-naphthoquinone; r⁶Is composed ofn is 0,1, 2,3, 4, 5, 6, 7, 8 or 9.

7. The method for preparing the quinone compound represented by the formula I as claimed in any one of claims 1 to 6, wherein when R is¹Is C₁～C₁₀When there is an alkyl group, said C₁～C₁₀Alkyl of (A) is C₁～C₄Alkyl groups of (a);

and/or when R¹Is C₂～C₁₀When said alkenyl is said C₂～C₁₀Alkenyl of (A) is C₂～C₅Alkenyl of (a);

and/or when R¹Is C₁～C₁₀Alkoxy of (2), said C₁～C₁₀Alkoxy of C₁～C₄Alkoxy group of (a);

and/or when R²Is C₁～C₁₀When there is an alkyl group, said C₁～C₁₀Alkyl of (A) is C₁～C₄Alkyl groups of (a);

and/or when R²Is C₂～C₁₀When said alkenyl is said C₂～C₁₀Alkenyl of (A) is C₂～C₅Alkenyl of (a);

and/or when R²Is C₁～C₁₀Alkoxy of (2), said C₁～C₁₀Alkoxy of C₁～C₄Alkoxy group of (a);

and/or when R³Is C₁～C₁₀When there is an alkyl group, said C₁～C₁₀Alkyl of (A) is C₁～C₄Alkyl groups of (a);

and/or when R³Is C₂～C₁₀When said alkenyl is said C₂～C₁₀Alkenyl of (A) is C₂～C₅Alkenyl of (a);

and/or when R³Is C₁～C₁₀Alkoxy of (2), said C₁～C₁₀Alkoxy of C₁～C₄Alkoxy group of (a);

and/or when R²、R³And the carbon atoms to which they are attached form C₆～C₁₀Aryl of (2), said C₆～C₁₀Aryl of (a) is phenyl;

and/or when R²、R³And the carbon atoms to which they are attached together form C substituted by one or more hydroxy groups₆～C₁₀Aryl of (2), said C₆～C₁₀Aryl of (a) is phenyl;

and/or when R⁶Is C₃～C₁₀₀When the alkenyl group is the above-mentioned alkenyl group, the beta-position and the gamma-position of X are a double bond;

and/or when R⁶Is C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀The alkenyl group contains 1 to 15 double bonds;

and/or when R⁶Is represented by one or more R^6-1Substituted C₃～C₁₀₀When the alkenyl group is the above-mentioned alkenyl group, the beta-position and the gamma-position of X are a double bond;

and/or when R⁶Is represented by one or more R^6-1Substituted C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀The alkenyl group contains 1 to 15 double bonds;

and/or when R⁶To be multiple of R^6-1Substituted C₃～C₁₀₀When said alkenyl group is (b), said plurality is 2 or 3;

and/or when R^6-1Independently is C₆～C₁₀Aryl of (2), said C₆～C₁₀Aryl of (a) is phenyl;

and/or when R⁶Is C₃～C₁₀When the cycloalkenyl group is (a), the beta-position and the gamma-position of X are a double bond;

and/or when R⁶Is C₃～C₁₀Cycloalkenyl of (a), C₃～C₁₀The cycloalkenyl group of (a) contains 1-5 double bonds;

and/or when R⁶Is C₃～C₁₀Cycloalkenyl of (a), C₃～C₁₀Cycloalkenyl of (a) is C₃～C₆Cycloalkenyl group of (a);

and/or, when X is halogen, the halogen is chlorine, bromine or iodine.

8. The process for preparing a quinone compound of formula I as claimed in claim 7, wherein when R is¹Is C₁～C₁₀When there is an alkyl group, said C₁～C₁₀Alkyl of (a) is methyl;

and/or when R¹Is C₂～C₁₀When said alkenyl is said C₂～C₁₀Alkenyl of (a) is 3-methyl-2-buten-1-yl;

and/or when R¹Is C₁～C₁₀Alkoxy of (2), said C₁～C₁₀Alkoxy of (b) is methoxy;

and/or when R²Is C₁～C₁₀When there is an alkyl group, said C₁～C₁₀Alkyl of (a) is methyl;

and/or when R²Is C₂～C₁₀When said alkenyl is said C₂～C₁₀Alkenyl of (a) is 3-methyl-2-buten-1-yl;

and/or when R²Is C₁～C₁₀Alkoxy of (2), said C₁～C₁₀Alkoxy of (b) is methoxy;

and/or when R³Is C₁～C₁₀When there is an alkyl group, said C₁～C₁₀Alkyl of (a) is methyl;

and/or when R³Is C₂～C₁₀When said alkenyl is said C₂～C₁₀Alkenyl of (a) is 3-methyl-2-buten-1-yl;

and/or when R³Is C₁～C₁₀Alkoxy of (2), said C₁～C₁₀Alkoxy of (b) is methoxy;

and/or when R⁶Is C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀The alkenyl group of (a) contains 1,2, 3, 4, 5, 6, 7, 8, 9 or 10 double bonds;

and/or when R⁶Is C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀Alkenyl of (A) is C₅～C₁₀₀A terpenyl group of (a);

and/or when R⁶Is represented by one or more R^6-1Substituted C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀The alkenyl group of (a) contains 1,2, 3, 4, 5, 6, 7, 8, 9 or 10 double bonds;

and/or when R⁶Is represented by one or more R^6-1Substituted C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀Alkenyl of (A) is C₅～C₁₀₀A terpenyl group of (a);

and/or when R⁶Is C₃～C₁₀Cycloalkenyl of (a), C₃～C₁₀The cycloalkenyl group of (a) contains 1,2, 3, 4 or 5 double bonds.

9. The method of claim 8, wherein R is the number of R⁶Is C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀Alkenyl of is "n is 0 to 19;

and/or when R⁶Is represented by one or more R^6-1Substituted C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀Alkenyl of is "n is 0 to 19;

and/or when R⁶Is C₃～C₁₀Cycloalkenyl of (a), C₃～C₁₀Cycloalkenyl of

10. The method of claim 9, wherein R is the number of R⁶Is C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀Alkenyl of is "n is 0,1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19;

and/or when R⁶Is represented by one or more R^6-1Substituted C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀Alkenyl of is "n is 0,1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19.

11. The method of claim 10, wherein R is the number of R⁶Is to be an R^6-1Substituted C₃～C₁₀₀Said is substituted by one R^6-1Substituted C₃～C₁₀₀The alkenyl group of (a) is a 3-phenyl-2-propen-1-yl group.

12. The method for preparing a quinone compound represented by formula I according to claim 1, wherein said compound represented by formula I has any one of the following structures:

13. the method for preparing a quinone compound represented by the formula I as set forth in claim 1, wherein the condensation reaction is carried out in the presence of a protective gas;

and/or, the condensation reaction is carried out in an organic solvent, or, the condensation reaction is carried out under the condition of no solvent;

and/or the anion of the alkali is hydride, hydroxide, amino anion, carbonate, phosphate orR^xIs C₁～C₁₅Alkyl of (C)₃～C₁₀Or by one or more R^x-1Substituted C₁～C₅Alkyl groups of (a); r^x-1Independently of the others, hydroxy, or, by one or more C₁～C₃Alkyl-substituted C of₃～C₁₀Cycloalkenyl group of (a);

and/or, the cation of the alkali is alkali metal ion or alkaline earth metal ion;

and/or the molar ratio of the alkali to the compound shown as the formula II is (2-4): 1;

and/or the condensation reaction is carried out in the presence of an initiator, wherein the initiator isR^1-IIIs hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a); r^2-IIIs hydrogen、C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a); r^3-IIIs hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a); or, R²、R³And the carbon atoms to which they are attached form C₆～C₁₀Aryl of (a), C substituted by one or more hydroxy groups₆～C₁₀Aryl of (a), or 5-to 10-membered heteroaryl; the hetero atom in the heteroaryl is selected from one or more of N, O and S, and the number of the hetero atoms is 1,2 or 3; r^4-IIIs O; r^5-IIIs O;

and/or, the condensation reaction is carried out in the presence of a reducing agent;

and/or the molar ratio of the compound shown as the formula III to the compound shown as the formula II is (0.1-2.0): 1;

and/or the temperature of the condensation reaction is 35-100 ℃;

and/or the reaction time of the condensation reaction is 0.1 to 336 hours;

and/or the post-treatment of the condensation reaction comprises the following steps: removing solid, and performing column chromatography.

14. The method according to claim 13, wherein when the condensation reaction is carried out in the presence of a shielding gas, the shielding gas is an inert gas or nitrogen;

and/or, when the condensation reaction is carried out in an organic solvent, "the base is more basic than sodium phenolate" means: in the organic solvent, the alkali is stronger than sodium phenolate;

and/or, when the condensation reaction is carried out in an organic solvent, the organic solvent is a non-polar organic solvent;

and/or when the condensation reaction is carried out in an organic solvent, the molar volume ratio of the compound shown as the formula II to the organic solvent is 0.1-0.3 mol/L;

and/or the molar ratio of the base to the compound shown as the formula II is 2:1, 2.5:1 or 4: 1;

and/or, when the condensation reaction is carried out in the presence of an initiator, the molar ratio of the initiator to the compound of formula II is 0.01:1, 0.025:1, 0.05:1, 0.075:1, 0.10:1, 0.15:1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1, or 0.8: 1;

and/or, when the condensation reaction is carried out in the presence of a reducing agent, the reducing agent isR^7-1And R^7-2Independently is C₁～C₄Alkyl groups of (a);

and/or, when the condensation reaction is carried out in the presence of a reducing agent, the molar ratio of the reducing agent to the compound of formula II is 0.01:1, 0.025:1, 0.05:1, 0.075:1, 0.10:1, 0.15:1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1, or 0.8: 1;

and/or the molar ratio of the compound shown in the formula III to the compound shown in the formula II is 0.2:1, 0.4:1, 0.5:1, 1:1, 1.05:1, 1.65:1 or 1.70: 1;

and/or the condensation reaction temperature is 50 ℃, 60 ℃, 65 ℃,70 ℃, 75 ℃, 80 ℃, 85 ℃, 90 ℃ or 95 ℃;

and/or the post-treatment of the condensation reaction comprises the following steps: removing solid, and performing column chromatography; the method for removing the solid is centrifugation or filtration.

15. The method according to claim 14, wherein when the condensation reaction is carried out in the presence of a shielding gas, the shielding gas is nitrogen;

and/or, when the condensation reaction is carried out in an organic solvent, the organic solvent is a halogenated hydrocarbon solvent and/or a hydrocarbon solvent;

and/or when the condensation reaction is carried out in an organic solvent, the molar volume ratio of the compound shown as the formula II to the organic solvent is 0.1-0.2 mol/L;

and/or, when the condensation reaction is carried out in the presence of a reducing agent, the reducing agent is

16. The method according to claim 15, wherein when the condensation reaction is carried out in an organic solvent, and the organic solvent comprises a halogenated hydrocarbon solvent, the halogenated hydrocarbon solvent is a halogenated alkane solvent and/or a halogenated aromatic hydrocarbon solvent;

and/or, when the condensation reaction is carried out in an organic solvent, and the organic solvent comprises a hydrocarbon solvent, the hydrocarbon solvent is an alkane solvent and/or an aromatic hydrocarbon solvent.

17. The method according to claim 16, wherein when the condensation reaction is carried out in an organic solvent, the organic solvent comprises a halogenated hydrocarbon solvent, and the halogenated hydrocarbon solvent comprises a halogenated alkane solvent, the halogenated alkane solvent is dichloromethane and/or 1, 2-dichloroethane;

and/or, when the condensation reaction is carried out in an organic solvent, the organic solvent comprises a halogenated hydrocarbon solvent, and the halogenated hydrocarbon solvent comprises a halogenated aromatic hydrocarbon solvent, the halogenated aromatic hydrocarbon solvent is one or more of fluorobenzene, chlorobenzene, bromobenzene, iodobenzene, benzotrifluoride, o-dichlorobenzene, m-dichlorobenzene and p-dichlorobenzene, and can also be chlorobenzene or o-dichlorobenzene;

and/or, when the condensation reaction is carried out in an organic solvent, the organic solvent comprises a hydrocarbon solvent, and the hydrocarbon solvent comprises an alkane solvent, the alkane solvent is mineral oil;

and/or, when the condensation reaction is carried out in an organic solvent, the organic solvent comprises a hydrocarbon solvent, and the hydrocarbon solvent comprises an aromatic hydrocarbon solvent, the aromatic hydrocarbon solvent is one or more of benzene, toluene, o-xylene, p-xylene, m-xylene and mesitylene, and can also be toluene.

18. The method of claim 13, wherein the anion of the base is hydroxide, carbonate or carbonateR^xIs C₁～C₁₅Alkyl groups of (a);

and/or when R^xIs C₁～C₁₅When there is an alkyl group, said C₁～C₁₅The alkyl group of (A) is methyl, ethyl, isopropyl,R^x-2Is C₁～C₁₂Alkyl groups of (a);

and/or when R^xIs C₃～C₁₀In the case of a cycloalkyl group of (A), said C₃～C₁₀Cycloalkyl being bridged ring C₅～C₁₀Cycloalkyl groups of (a);

and/or when R^xIs represented by one or more R^x-1Substituted C₁～C₅Said plurality is 2,3 or 4 when said alkyl group is (a);

and/or when R^x-1Independently by one or more C₁～C₃Alkyl-substituted C of₃～C₁₀Cycloalkenyl of (a), C₁～C₃Alkyl of (a) is methyl;

and/or when R^x-1Independently by one or more C₁～C₃Alkyl-substituted C of₃～C₁₀Cycloalkenyl of (a), C₃～C₁₀The cycloalkenyl group of (A) is monocyclic C₃～C₆Cycloalkenyl group of (a);

and/or when R^xIs represented by one or more R^x-1Substituted C₁～C₅When there is an alkyl group, said C₁～C₅Alkyl of (a) is n-propyl, isopropyl or neopentyl;

and/or, when the cation of the alkali is an alkali metal ion, the alkali metal ion is a lithium ion, a sodium ion or a potassium ion;

and/or, when the cation of the alkali is alkaline earth metal ion, the alkaline earth metal ion is magnesium ion or calcium ion.

19. The method of claim 18, wherein the quinone compound of formula I,li, andthe carbon atom to which it is attached is a tertiary carbon atom;

and/or when C₁～C₁₅Alkyl of (A) isWhen R is in the above-mentioned range^x-2Is C₁～C₁₂The linear alkyl group of (1);

and/or when R^xIs C₃～C₁₀In the case of a cycloalkyl group of (A), said C₃～C₁₀Cycloalkyl of (a) is adamantyl;

and/or when R^x-1Independently by one or more C₁～C₃Alkyl-substituted C of₃～C₁₀With one or more C₁～C₃Alkyl-substituted C of₃～C₁₀Cycloalkenyl of

20. The method of claim 19, wherein when C is C, the quinone compound of formula I is prepared₁～C₁₅Alkyl of (A) isWhen R is in the above-mentioned range^x-2Is C₁～C₇The linear alkyl group of (1);

and/or when R^xIs C₃～C₁₀In the case of a cycloalkyl group of (A), said C₃～C₁₀Cycloalkyl of

21. The method of claim 20, wherein when C is C, the quinone compound of formula I is prepared₁～C₁₅Alkyl of (A) isWhen is in use, theIs tert-butyl,

22. The method of claim 18, wherein the base is selected from one or more of the following group: alkali metal hydrides, alkali metal hydroxides, alkali metal carbonates and alkali metalsAnd (3) salt.

23. The method of claim 18, wherein the base is selected from one or more of the following group: sodium hydride, sodium hydroxide, sodium carbonate, potassium carbonate,Sodium salt anda potassium salt.

24. The method of claim 18, wherein the base is selected from one or more of the following group: sodium hydroxide, sodium carbonate, potassium carbonate,Sodium salt anda potassium salt.

25. The method of claim 23 or 24, wherein when said base comprises sodium hydroxide, said sodium hydroxide is generated in situ from water and sodium hydride;

and/or, when said base comprisesWhen the sodium salt is mentionedThe sodium salt is sodium methoxide, sodium 2-methyl-2-nonanolate, sodium tert-butoxide, sodium 1-adamantanolate, sodium isopropoxide, sodium ethoxide, sodium terpineolate, sodium 3-ethyl-3-pentanolate, sodium 2-methyl-2-hexanolate, sodium 1, 3-propanediol, sodium glycerolate, sodium tert-butoxide, sodium ethoxide, sodium methoxide, sodium ethoxide, sodium methoxide, sodium methoxide, sodium methoxide, sodium methoxide, sodium methoxide, sodium methoxide, sodium methoxide, sodium methoxide, sodium methoxide, sodium methoxide, sodium methoxide, sodium methoxide, sodium methoxide, sodium methoxide,Sodium pentaerythritol or sodium 2-methyl-2-pentanolate;

and/or, when said base comprisesWhen the potassium salt is present, theThe potassium salt is potassium methoxide, potassium 2-methyl-2-nonanoate, potassium tert-butoxide, potassium 1-adamantanolate, potassium isopropoxide, potassium ethoxide, potassium terpineolate, potassium 3-ethyl-3-pentanolate, potassium 2-methyl-2-hexanoate, potassium 1, 3-propanediol, potassium glycerolate, potassium pentaerythritol or potassium 2-methyl-2-pentanolate;

and/or, when said base comprisesWhen the sodium salt is mentionedSodium salt ofIn situ generation with sodium hydride;

and/or, when said base comprisesWhen the potassium salt is present, theThe potassium salt is prepared fromGenerated in situ with potassium hydride.

26. The method of claim 25, wherein when said base comprises sodium hydroxide and said sodium hydroxide is generated in situ from water and sodium hydride, said amount of water is a catalytic amount and said molar amount of sodium hydride is the same as said molar amount of base;

and/or, when said base comprisesSodium salt of the compoundSodium salt ofWhen generated in situ with sodium hydride, saidThe amount of (A) is a catalytic amount, and the molar amount of the sodium hydride is the same as that of the base.

27. The method of claim 26, wherein when the amount of water is a catalytic amount, the catalytic amount is: the molar ratio of the water to the compound shown as the formula II is (0.08-0.15): 1, e.g. 0.10: 1;

and/or, when saidWhen the amount of (a) is a catalytic amount, the catalytic amount means: saidThe molar ratio of the compound to the compound shown in the formula II is (0.03-0.3): 1, e.g. 0.03: 1. 0.05: 1. 0.06: 1. 0.07: 1. 0.123: 1. 0.125: 1. 0.165: 1. 0.25: 1 or 0.3: 1.

28. the method of claim 13, wherein R is the number of R^1-IIIs C₁～C₁₀When there is an alkyl group, said C₁～C₁₀Alkyl of (A) is C₁～C₄Alkyl groups of (a);

and/or when R^1-IIIs C₂～C₁₀When said alkenyl is said C₂～C₁₀Alkenyl of (A) is C₂～C₅Alkenyl of (a);

and/or when R^1-IIIs C₁～C₁₀Alkoxy of (2), said C₁～C₁₀Alkoxy of C₁～C₄Alkoxy group of (a);

and/or when R^2-IIIs C₁～C₁₀When there is an alkyl group, said C₁～C₁₀Alkyl of (A) is C₁～C₄Alkyl groups of (a);

and/or when R^2-IIIs C₂～C₁₀When said alkenyl is said C₂～C₁₀Alkenyl of (A) is C₂～C₅Alkenyl of (a);

and/or when R^2-IIIs C₁～C₁₀Alkoxy of (2), said C₁～C₁₀Alkoxy of C₁～C₄Alkoxy group of (a);

and/or when R^3-IIIs C₁～C₁₀When there is an alkyl group, said C₁～C₁₀Alkyl of (A) is C₁～C₄Alkyl groups of (a);

and/or when R^3-IIIs C₂～C₁₀When said alkenyl is said C₂～C₁₀Alkenyl of (A) is C₂～C₅Alkenyl of (a);

and/or when R^3-IIIs C₁～C₁₀Alkoxy of (2), said C₁～C₁₀Alkoxy of C₁～C₄Alkoxy group of (a);

and/or when R^2-II、R^3-IIAnd the carbon atoms to which they are attached form C₆～C₁₀Aryl of (2), said C₆～C₁₀Aryl of (a) is phenyl;

and/or when R^2-II、R^3-IIAnd the carbon atoms to which they are attached together form C substituted by one or more hydroxy groups₆～C₁₀Aryl of (2), said C₆～C₁₀Aryl of (a) is phenyl;

and/or, said R^1-IIAnd said R¹The same; said R^2-IIAnd said R²The same; said R^3-IIAnd said R³The same is true.

29. The method of claim 28, wherein R is the number of R^1-IIIs C₁～C₁₀When there is an alkyl group, said C₁～C₁₀Alkyl of (a) is methyl;

and/or when R^1-IIIs C₂～C₁₀When said alkenyl is said C₂～C₁₀Alkenyl of (a) is 3-methyl-2-buten-1-yl;

and/or when R^1-IIIs C₁～C₁₀Alkoxy of (2), said C₁～C₁₀Alkoxy of (b) is methoxy;

and/or when R^2-IIIs C₁～C₁₀When there is an alkyl group, said C₁～C₁₀Alkyl of (a) is methyl;

and/or when R^2-IIIs C₂～C₁₀When said alkenyl is said C₂～C₁₀Alkenyl of (a) is 3-methyl-2-buten-1-yl;

and/or when R^2-IIIs C₁～C₁₀Alkoxy of (2), said C₁～C₁₀Alkoxy of (b) is methoxy;

and/or when R^3-IIIs C₁～C₁₀When there is an alkyl group, said C₁～C₁₀Alkyl of (a) is methyl;

and/or when R^3-IIIs C₂～C₁₀When said alkenyl is said C₂～C₁₀Alkenyl of (a) is 3-methyl-2-buten-1-yl;

and/or when R^3-IIIs C₁～C₁₀Alkoxy of (2), said C₁～C₁₀The alkoxy group of (b) is methoxy.

30. The method of claim 29, wherein the quinone compound of formula I is prepared byIs 1, 4-hydroquinone.

31. A process for the preparation of quinone compounds of formula I according to claim 1, wherein said condensation reaction has the reaction parameters according to any one of the following schemes:

scheme A:

the condensation reaction is carried out in the presence of protective gas; the condensation reaction is carried out in an organic solvent, the organic solvent is a halogenated aromatic hydrocarbon solvent, and the molar volume ratio of the compound shown as the formula II to the organic solvent is 0.1-0.3 mol/L; the alkali is sodium hydroxide orSodium salt, R^xIs composed ofR^x-2Is C₁～C₇The molar ratio of the alkali to the compound shown as the formula II is (2-4): 1; the condensation reaction is carried out inIn the presence of a catalyst, saidThe molar ratio of the compound to the compound shown in the formula II is (0.025-0.10): 1; the molar ratio of the compound shown as the formula III to the compound shown as the formula II is (0.2)2.0): 1; the temperature of the condensation reaction is 40-100 ℃;

scheme B:

the condensation reaction is carried out in the presence of nitrogen; the condensation reaction is carried out in chlorobenzene or o-dichlorobenzene, and the molar volume ratio of the compound shown as the formula II to the chlorobenzene or o-dichlorobenzene is 0.1-0.2 mol/L; the base isSodium salt, R^xIs tert-butyl, The molar ratio of the alkali to the compound shown as the formula II is (2-2.5): 1; the condensation reaction is carried out inIn the presence of a catalyst, saidThe molar ratio of the compound to the compound shown in the formula II is (0.05-0.10): 1; the molar ratio of the compound shown as the formula III to the compound shown as the formula II is (0.2-1.70): 1; the temperature of the condensation reaction is 70-80 ℃;

scheme C:

the condensation reaction is carried out in the presence of nitrogen; the condensation reaction is carried out in chlorobenzene or o-dichlorobenzene, and the molar volume ratio of the compound shown as the formula II to the chlorobenzene or o-dichlorobenzene is 0.1-0.2 mol/L; the base is sodium hydride andsodium salt, R^xIs composed of Is tert-butyl,The molar ratio of the alkali to the compound shown as the formula II is (2-2.5): 1; the condensation reaction is also described inIn the presence of a catalyst, saidThe molar ratio of the compound to the compound shown in the formula II is (0.05-0.10): 1; the molar ratio of the compound shown as the formula III to the compound shown as the formula II is (0.2-1.70): 1; the temperature of the condensation reaction is 70-80 ℃;

scheme D:

the condensation reaction is carried out in the presence of nitrogen; the condensation reaction is carried out in chlorobenzene or o-dichlorobenzene, and the molar volume ratio of the compound shown as the formula II to the chlorobenzene or o-dichlorobenzene is 0.1-0.2 mol/L; the base is sodium hydride andR^xis composed of Is tert-butyl,The molar ratio of the alkali to the compound shown as the formula II is (2-2.5): 1, theThe molar ratio of the compound to the compound shown in the formula II is (0.03-0.3): 1; the condensation reaction is also described inIn the presence of a catalyst, saidThe molar ratio of the compound to the compound shown in the formula II is (0.05-0.10): 1; the molar ratio of the compound shown as the formula III to the compound shown as the formula II is (0.2-1.70): 1; the temperature of the condensation reaction is 70-80 ℃.

Technical Field

The invention relates to a preparation method of quinone compounds.

Background

The benzoquinone compound has unique structural and functional characteristics, widely exists in nature and plays an important role. The compounds of coenzyme Q10, vitamin K, plastoquinone and the like containing quinone functional groups are electron transfer carriers in biochemical processes of eukaryotic respiration, photosynthesis and the like. Research shows that coenzyme Q10 and vitamin K are indispensable vitamins in human body and have positive effect on organs and tissues such as heart, skeleton and the like, but the food sources of the vitamins are limited, so that chemical synthesis is an important source of the vitamins, and the market potential of a successful synthesis method is huge.

The classical method for synthesizing quinone compounds generally adopts phenol, aryl ether and other raw materials, carries out side chain modification through functional reactions such as Lewis acid, metal catalytic coupling and the like, and then carries out deprotection and oxidation on the aryl ether, wherein the reactions use more catalysts, protecting group reagents and oxidants, and have longer steps and lower efficiency.

Therefore, the development of a novel method for synthesizing the quinone compound, which is simple, convenient, efficient and widely applicable, is of great significance.

Disclosure of Invention

The invention aims to solve the technical problem that the existing preparation method of the quinone compound is single, so that the invention provides a preparation method of the quinone compound. The method is simple to operate and suitable for industrial production.

The invention provides a preparation method of a quinone compound shown as a formula I, which comprises the following steps: in the presence of alkali, carrying out condensation reaction on a compound shown as a formula II and a compound shown as a formula III to obtain a quinone compound shown as a formula I; the alkalinity of the alkali is stronger than that of sodium phenolate;

wherein R is¹Is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

R²is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

R³is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

R⁴is O;

R⁵is O;

R⁶is C₃～C₁₀₀By one or more R^6-1Substituted C₃～C₁₀₀Or, C₃～C₁₀Cycloalkenyl group of (a);

x is halogen.

In one embodiment, some features of the above-described preparation method are as follows, and the remaining features are as described in any one of the above-described or below (hereinafter referred to as "in one embodiment"): r¹Is hydrogen, C₁～C₁₀Alkyl or C₁～C₁₀Alkoxy group of (2).

In a certain embodiment, R²Is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

R³is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

or, R²、R³And the carbon atoms to which they are attached form C₆～C₁₀Aryl of (a), or C substituted by one or more hydroxy groups₆～C₁₀Aryl group of (1).

In a certain embodiment, R²Is hydrogen, C₁～C₁₀Alkyl or C₁～C₁₀Alkoxy group of (a);

R³is hydrogen, C₁～C₁₀Alkyl or C₁～C₁₀Alkoxy group of (a);

or, R²、R³And the carbon atoms to which they are attached form C₆～C₁₀Aryl of (a), or C substituted by one or more hydroxy groups₆～C₁₀Aryl group of (1).

In a certain embodiment, R²Is hydrogen, C₁～C₄Alkyl or C₁～C₄Alkoxy group of (a);

R³is hydrogen, C₁～C₄Alkyl or C₁～C₄Alkoxy group of (a);

or, R²、R³And the carbon atoms to which they are attached together form a phenyl group, or a phenyl group substituted with one or more hydroxyl groups.

In a certain embodiment, R⁶Is C₃～C₁₀₀Alkenyl groups of (a).

In a certain embodiment, R⁶Is chlorophyllin n is 0 to 9 (e.g., 0,1, 2,3, 4, 5, 6, 7, 8, or 9).

In a certain embodiment, R^6-1Independently is C₆～C₁₀Aryl group of (1).

In a certain embodiment, R¹、R²And R³At most one of which is hydrogen.

In a certain embodiment, R¹、R²And R³One of which is hydrogen.

In a certain embodiment, R¹Is hydrogen, R²And R³Is not hydrogen.

In a certain embodiment, R²Is hydrogen, R¹And R³Is not hydrogen.

In a certain embodiment, R³Is hydrogen, R¹And R²Is not hydrogen.

In a certain embodiment, R¹、R²And R³Are not all hydrogen.

In a certain embodiment, R¹、R²And R³Two of which are hydrogen.

In a certain embodiment, R¹、R²And R³Are all hydrogen.

In a certain embodiment, R¹Is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

R²is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

R³is hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

or, R²、R³And the carbon atoms to which they are attached form C₆～C₁₀Aryl of (a), or C substituted by one or more hydroxy groups₆～C₁₀Aryl of (a);

R⁴is O;

R⁵is O;

R⁶is C₃～C₁₀₀By one or more R^6-1Substituted C₃～C₁₀₀Or, C₃～C₁₀Cycloalkenyl group of (a);

R^6-1independently is C₆～C₁₀Aryl of (a);

x is halogen.

In a certain embodiment, R¹Is hydrogen, C₁～C₁₀Alkyl or C₁～C₁₀Alkoxy group of (a);

R²is hydrogen、C₁～C₁₀Alkyl or C₁～C₁₀Alkoxy group of (a);

R³is hydrogen, C₁～C₁₀Alkyl or C₁～C₁₀Alkoxy group of (a);

or, R²、R³And the carbon atoms to which they are attached form C₆～C₁₀Aryl of (a), or C substituted by one or more hydroxy groups₆～C₁₀Aryl of (a);

R⁴is O;

R⁵is O;

R⁶is C₃～C₁₀₀Alkenyl of (a);

x is halogen.

In a certain embodiment, R¹Is hydrogen, C₁～C₄Alkyl or C₁～C₄Alkoxy group of (a);

R²is hydrogen, C₁～C₄Alkyl or C₁～C₄Alkoxy group of (a);

R³is hydrogen, C₁～C₄Alkyl or C₁～C₄Alkoxy group of (a);

or, R²、R³And the carbon atoms to which they are attached together form a phenyl group, or a phenyl group substituted with one or more hydroxyl groups;

R⁴is O;

R⁵is O;

R⁶is chlorophyllinn is 0 to 9 (e.g., 0,1, 2,3, 4, 5, 6, 7, 8, or 9);

x is halogen.

In a certain embodiment, the compound represented by formula II may be 1, 4-benzoquinone, 2-methyl-1, 4-benzoquinone, 2, 3-dimethyl-1, 4-benzoquinone, 2,3, 5-trimethyl-1, 4-benzoquinone, 2, 3-dimethoxy-5-methyl-1, 4-benzoquinone, 2-methyl-1, 4-naphthoquinone, or 5-hydroxy-1, 4-naphthoquinone;

R⁶is 3-methyl-2-buten-1-yl(all-E) -3, 7-dimethyl-2, 6-octadien-1-yl(all-E) -3,7, 11-trimethyl-2, 6, 10-dodecatrien-1-ylChlorophyll base(all-E) -3,7,11, 15-tetramethyl-2, 6,10, 14-hexadecatetetraen-1-yl(all-E) -3,7,11,15,19,23, 27-heptamethyl-2, 6,10,14,18,22, 26-dioctadecylheptaen-1-yl(all-E) -3,7,11,15,19,23,27,31, 35-nonamethyl-2, 6,10,14,18,22,26,30, 34-trihexadecanonaen-1-ylOr (all-E) -3,7,11,15,19,23,27,31,35, 39-decamethyl-2, 6,10,14,18,22,26,30,34, 38-forty-decaen-1-yl

In a certain scheme, the compound shown in the formula II can be 2, 3-dimethoxy-5-methyl-1, 4-benzoquinone; r⁶Is composed ofn is 0,1, 2,3, 4, 5, 6, 7, 8 or 9.

In a certain scheme, the compound shown in the formula II can be 2, 3-dimethoxy-5-methyl-1, 4-benzoquinone; r⁶Is composed ofn is 0,1, 2,3, 4, 5, 6, 7, 8 or 9;

the condensation reaction may have the following reaction parameters: the condensation reaction is carried out in the presence of nitrogen; the condensation reaction is carried out in chlorobenzene or o-dichlorobenzene, and the molar volume ratio of the compound shown as the formula II to the chlorobenzene or o-dichlorobenzene is 0.1-0.2 mol/L; the base is sodium hydride andsodium salt, R^xIs composed ofIs tert-butyl, The molar ratio of the alkali to the compound shown as the formula II is (2-2.5): 1; the condensation reaction is also described inIn the presence of a catalyst, saidThe molar ratio of the compound to the compound shown in the formula II is (0.05-0.10): 1; the molar ratio of the compound shown as the formula III to the compound shown as the formula II is (0.2-1.70): 1; the temperature of the condensation reaction is 70-80 ℃.

In a certain scheme, the compound shown in the formula II can be 2, 3-dimethoxy-5-methyl-1, 4-benzoquinone; r⁶Is composed ofn is 0,1, 2,3, 4, 5, 6, 7, 8 or 9;

said condensationThe reaction may have the following reaction parameters: the condensation reaction is carried out in the presence of nitrogen; the condensation reaction is carried out in chlorobenzene or o-dichlorobenzene, and the molar volume ratio of the compound shown as the formula II to the chlorobenzene or o-dichlorobenzene is 0.1-0.2 mol/L; the base is sodium hydride andR^xis composed ofIs tert-butyl, The molar ratio of the alkali to the compound shown as the formula II is (2-2.5): 1, theThe molar ratio of the compound to the compound shown in the formula II is (0.03-0.3): 1; the condensation reaction is also described inIn the presence of a catalyst, saidThe molar ratio of the compound to the compound shown in the formula II is (0.05-0.10): 1; the molar ratio of the compound shown as the formula III to the compound shown as the formula II is (0.2-1.70): 1; the temperature of the condensation reaction is 70-80 ℃.

In one embodiment, the compound of formula II can be 2-methyl-1, 4-naphthoquinone; r⁶Is composed ofn is 0,1, 2,3, 4, 5, 6, 7, 8 or 9.

In one embodiment, the formula IIThe compound can be 2-methyl-1, 4-naphthoquinone; r⁶Is composed ofn is 0,1, 2,3, 4, 5, 6, 7, 8 or 9;

In one embodiment, the compound of formula II can be 2-methyl-1, 4-naphthoquinone; r⁶Is composed ofn is 0,1, 2,3, 4, 5, 6, 7, 8 or9；

The condensation reaction may have the following reaction parameters: the condensation reaction is carried out in the presence of nitrogen; the condensation reaction is carried out in chlorobenzene or o-dichlorobenzene, and the molar volume ratio of the compound shown as the formula II to the chlorobenzene or o-dichlorobenzene is 0.1-0.2 mol/L; the base is sodium hydride andR^xis composed ofIs tert-butyl, The molar ratio of the alkali to the compound shown as the formula II is (2-2.5): 1, theThe molar ratio of the compound to the compound shown in the formula II is (0.03-0.3): 1; the condensation reaction is also described inIn the presence of a catalyst, saidThe molar ratio of the compound to the compound shown in the formula II is (0.05-0.10): 1; the molar ratio of the compound shown as the formula III to the compound shown as the formula II is (0.2-1.70): 1; the temperature of the condensation reaction is 70-80 ℃.

In one embodiment, when R¹Is C₁～C₁₀When there is an alkyl group, said C₁～C₁₀The alkyl group of (A) may be C₁～C₄The alkyl group of (b) may be a methyl group.

In one embodiment, when R¹Is C₂～C₁₀When said alkenyl is said C₂～C₁₀The alkenyl group of (A) may be C₂～C₅The alkenyl group of (a) may also be 3-methyl-2-buten-1-yl

In one embodiment, when R¹Is C₁～C₁₀Alkoxy of (2), said C₁～C₁₀The alkoxy group of (A) may be C₁～C₄The alkoxy group of (b) may be a methoxy group.

In one embodiment, when R²Is C₁～C₁₀When there is an alkyl group, said C₁～C₁₀The alkyl group of (A) may be C₁～C₄The alkyl group of (b) may be a methyl group.

In one embodiment, when R²Is C₂～C₁₀When said alkenyl is said C₂～C₁₀The alkenyl group of (A) may be C₂～C₅The alkenyl group of (a) may also be 3-methyl-2-buten-1-yl

In one embodiment, when R²Is C₁～C₁₀Alkoxy of (2), said C₁～C₁₀The alkoxy group of (A) may be C₁～C₄The alkoxy group of (b) may be a methoxy group.

In one embodiment, when R³Is C₁～C₁₀When there is an alkyl group, said C₁～C₁₀The alkyl group of (A) may be C₁～C₄The alkyl group of (b) may be a methyl group.

In one embodiment, when R³Is C₂～C₁₀When said alkenyl is said C₂～C₁₀The alkenyl group of (A) may be C₂～C₅The alkenyl group of (a) may also be 3-methyl-2-buten-1-yl

In one embodiment, when R³Is C₁～C₁₀Alkoxy of (2), said C₁～C₁₀The alkoxy group of (A) may be C₁～C₄The alkoxy group of (b) may be a methoxy group.

In one embodiment, when R²、R³And the carbon atoms to which they are attached form C₆～C₁₀Aryl of (2), said C₆～C₁₀The aryl group of (a) may be phenyl.

In one embodiment, when R²、R³And the carbon atoms to which they are attached together form C substituted by one or more hydroxy groups₆～C₁₀Aryl of (2), said C₆～C₁₀The aryl group of (a) may be phenyl.

In one embodiment, the compound represented by formula II may be 1, 4-benzoquinone, 2-methyl-1, 4-benzoquinone, 2-methoxy-1, 4-benzoquinone, 2, 3-dimethyl-1, 4-benzoquinone, 2, 6-dimethyl-3- (3-methyl-2-buten-1-yl) -1, 4-benzoquinone, 2,3, 5-trimethyl-1, 4-benzoquinone, 2, 3-dimethoxy-5-methyl-1, 4-benzoquinone, 2-methyl-1, 4-naphthoquinone, or 5-hydroxy-1, 4-naphthoquinone.

In one embodiment, when R⁶Is C₃～C₁₀₀In the case of the alkenyl group of (3), the beta-and gamma-positions of X may be a double bond together.

In one embodiment, when R⁶Is C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀The alkenyl group of (a) may contain 1 to 15 double bonds, and may further contain 1,2, 3, 4, 5, 6, 7, 8, 9 or 10 double bonds.

In one embodiment, when R⁶Is C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀The alkenyl group of (A) may be C₅～C₁₀₀Can also be "n is 0 to 19 (e.g., 0,1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11)12, 13, 14, 15, 16, 17, 18 or 19, further for example 0,1, 2,3, 4, 5, 6, 7, 8 or 9) ".

In one embodiment, when R⁶Is C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀The alkenyl group of (A) may be C₃～C₅₀May also be C₃Alkenyl of, C₄Alkenyl of, C₅Alkenyl of, C₆Alkenyl of, C₇Alkenyl of, C₈Alkenyl of, C₉Alkenyl of, C₁₀Alkenyl of, C₁₅Alkenyl of, C₂₀Alkenyl of, C₃₀Alkenyl of, C₄₀Alkenyl of, C₄₅Alkenyl or C₅₀The alkenyl group of (A) may further be allyl or 2-buten-1-yl3-methyl-2-buten-1-yl2-hexen-1-yl(all-E) -3, 7-dimethyl-2, 6-octadien-1-yl(all-E) -3,7, 11-trimethyl-2, 6, 10-dodecatrien-1-ylChlorophyll base(all-E) -3,7,11, 15-tetramethyl-2, 6,10, 14-hexadecatetetraen-1-yl(all-E) -3,7,11,15,19,23, 27-heptamethyl-2, 6,10,14,18,22, 26-dioctadecylheptaen-1-yl(all-E) -3,7,11,15,19,23,27,31, 35-nonamethyl-2, 6,10,14,18,22,26,30, 34-trihexadecanonaen-1-ylOr (all-E) -3,7,11,15,19,23,27,31,35, 39-decamethyl-2, 6,10,14,18,22,26,30,34, 38-forty-decaen-1-yl

In one embodiment, when R⁶Is represented by one or more R^6-1Substituted C₃～C₁₀₀In the case of the alkenyl group of (3), the beta-and gamma-positions of X may be a double bond together.

In one embodiment, when R⁶Is represented by one or more R^6-1Substituted C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀The alkenyl group(s) may contain 1 to 15 double bonds, and may also contain 1,2, 3, 4, 5, 6, 7, 8, 9 or 10 double bonds.

In one embodiment, when R⁶Is represented by one or more R^6-1Substituted C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀The alkenyl group of (A) may be C₅～C₁₀₀Can also be "n is 0 to 19 (e.g., 0,1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 19, further e.g., 0,1, 2,3, 4, 5, 6, 7, 8, or 9) ".

In one embodiment, when R⁶Is represented by one or more R^6-1Substituted C₃～C₁₀₀When said alkenyl is said C₃～C₁₀₀The alkenyl group of (A) may be C₃～C₅₀May also be C₃Alkenyl of, C₄Alkenyl of, C₅Alkenyl of, C₆Alkenyl of, C₇Alkenyl of, C₈Alkenyl of, C₉Alkenyl of (2)、C₁₀Alkenyl of, C₁₅Alkenyl of, C₂₀Alkenyl of, C₃₀Alkenyl of, C₄₀Alkenyl of, C₄₅Alkenyl or C₅₀The alkenyl group of (A) may further be allyl or 2-buten-1-yl3-methyl-2-buten-1-yl2-hexen-1-yl(all-E) -3, 7-dimethyl-2, 6-octadien-1-yl(all-E) -3,7, 11-trimethyl-2, 6, 10-dodecatrien-1-ylChlorophyll base(all-E) -3,7,11, 15-tetramethyl-2, 6,10, 14-hexadecatetetraen-1-yl(all-E) -3,7,11,15,19,23, 27-heptamethyl-2, 6,10,14,18,22, 26-dioctadecylheptaen-1-yl(all-E) -3,7,11,15,19,23,27,31, 35-nonamethyl-2, 6,10,14,18,22,26,30, 34-trihexadecanonaen-1-ylOr (all-E) -3,7,11,15,19,23,27,31,35, 39-decamethyl-2, 6,10,14,18,22,26,30,34, 38-forty-decaen-1-yl

In one embodiment, when R⁶To be multiple of R^6-1Substituted C₃～C₁₀₀When the alkenyl group is (b), the plural number may be 2 or 3.

In one embodiment, when R^6-1Independently is C₆～C₁₀Aryl of (2), said C₆～C₁₀The aryl group of (a) may be phenyl.

In one embodiment, when R⁶Is to be an R^6-1Substituted C₃～C₁₀₀Said is substituted by one R^6-1Substituted C₃～C₁₀₀May be substituted by one R^6-1Substituted C₃～C₅₀The alkenyl group of (a) may also be a 3-phenyl-2-propen-1-yl group

In one embodiment, when R⁶Is C₃～C₁₀The cycloalkenyl group of (1) above, the beta-and gamma-positions of X may be a double bond together.

In one embodiment, when R⁶Is C₃～C₁₀Cycloalkenyl of (a), C₃～C₁₀The cycloalkenyl group of (a) may contain 1 to 5 double bonds, and may also contain 1,2, 3, 4 or 5 double bonds.

In one embodiment, when R⁶Is C₃～C₁₀Cycloalkenyl of (a), C₃～C₁₀The cycloalkenyl group of (A) may be C₃～C₆May also be 2-cyclohexen-1-yl

In a certain embodiment, when X is halogen, the halogen may be chlorine, bromine or iodine, and may also be chlorine or bromine.

In one embodiment, the compound of formula I can be of any of the following structures:

in one embodiment, the condensation reaction may also be carried out in the presence of a protective gas.

In one embodiment, the protective gas may be an inert gas or nitrogen, and may also be nitrogen.

In one embodiment, the condensation reaction may be carried out in an organic solvent or in the absence of a solvent.

In one aspect, when the condensation reaction can be carried out in an organic solvent, "the base is more basic than sodium phenate" means: in the organic solvent, the alkali is stronger than sodium phenolate.

In one embodiment, when the condensation reaction can be carried out in an organic solvent, the organic solvent is an organic solvent conventionally used in the condensation reaction of this type in the art, and can dissolve other materials.

In one embodiment, the organic solvent may be a nonpolar organic solvent, and may also be a halogenated hydrocarbon solvent and/or a hydrocarbon solvent.

In one embodiment, the halogenated hydrocarbon solvent may be a halogenated alkane solvent and/or a halogenated aromatic hydrocarbon solvent.

In one embodiment, the haloalkane solvent can be dichloromethane and/or 1, 2-dichloroethane.

In a certain embodiment, the halogenated aromatic hydrocarbon solvent may be one or more of fluorobenzene, chlorobenzene, bromobenzene, iodobenzene, benzotrifluoride, o-dichlorobenzene, m-dichlorobenzene and p-dichlorobenzene, and may also be chlorobenzene or o-dichlorobenzene.

In one embodiment, the hydrocarbon solvent may be an alkane solvent and/or an aromatic hydrocarbon solvent.

In one embodiment, the alkane solvent may be mineral oil.

In one embodiment, the aromatic hydrocarbon solvent may be one or more of benzene, toluene, o-xylene, p-xylene, m-xylene, and mesitylene, and may also be toluene.

In a certain scheme, the dosage of the organic solvent is based on the dosage of dissolving other materials.

In one embodiment, when the condensation reaction can be performed in an organic solvent, the molar volume ratio of the compound represented by the formula II to the organic solvent may be 0.1mol/L to 0.3mol/L, or may be 0.1mol/L to 0.2 mol/L.

In one embodiment, the anion of the base can be hydride, hydroxide, amino anion, carbonate, phosphate, or

R^xIs C₁～C₁₅Alkyl of (C)₃～C₁₀Or by one or more R^x-1Substituted C₁～C₅Alkyl groups of (a); r^x-1Independently of the others, hydroxy, or, by one or more C₁～C₃Alkyl-substituted C of₃～C₁₀The cycloalkenyl group of (1).

In one embodiment, the anion of the base can be hydroxide, carbonate orR^xIs C₁～C₁₅Alkyl group of (1).

In one aspect of the present invention,li, andthe carbon atom to which it is attached is a tertiary carbon atom.

In one embodiment, when R^xIs C₁～C₁₅When there is an alkyl group, said C₁～C₁₅The alkyl group of (A) may be methyl, ethyl, isopropyl,R^x-2Is C₁～C₁₂Alkyl group of (1).

In one embodiment, when C₁～C₁₅Alkyl of (A) isWhen R is in the above-mentioned range^x-2Can be C₁～C₁₂Linear alkyl group of (1).

In one embodiment, when C₁～C₁₅Alkyl of (A) isWhen R is in the above-mentioned range^x-2Can be C₁～C₇Linear alkyl group of (1).

In one embodiment, when C₁～C₁₅Alkyl of (A) isWhen is in use, theMay be a tert-butyl group,

In one embodiment, when R^xIs C₃～C₁₀In the case of a cycloalkyl group of (A), said C₃～C₁₀The cycloalkyl group of (A) may be a bridged ring C₅～C₁₀Cycloalkyl of (2), which may in turn be adamantyl (e.g.))。

In one embodiment, when R^xIs represented by one or more R^x-1Substituted C₁～C₅When said alkyl group(s) is (are), said plurality may be 2 or 3Or 4.

In one embodiment, when R^x-1Independently by one or more C₁～C₃Alkyl-substituted C of₃～C₁₀Cycloalkenyl of (a), C₁～C₃The alkyl group of (a) may be a methyl group.

In one embodiment, when R^x-1Independently by one or more C₁～C₃Alkyl-substituted C of₃～C₁₀Cycloalkenyl of (a), C₃～C₁₀The cycloalkenyl group of (A) can be monocyclic C₃～C₆The cycloalkenyl group of (a) can also be cyclohexenyl.

In one embodiment, when R^x-1Independently by one or more C₁～C₃Alkyl-substituted C of₃～C₁₀With one or more C₁～C₃Alkyl-substituted C of₃～C₁₀The cycloalkenyl group of (A) can be

In one embodiment, when R^xIs represented by one or more R^x-1Substituted C₁～C₅When there is an alkyl group, said C₁～C₅The alkyl group of (a) may be n-propyl, isopropyl or neopentyl.

In one embodiment, the cation of the base may be an alkali metal ion or an alkaline earth metal ion.

In one embodiment, the alkali metal ion may be lithium ion, sodium ion or potassium ion.

In one embodiment, the alkaline earth metal ion may be magnesium ion or calcium ion.

In one embodiment, the base may be selected from one or more (e.g., 2,3, 4, or 5) of the following groups: alkali metal hydrides, alkali metal hydroxides, alkali metal carbonates and alkali metalsSalt, more preferably selected fromOne or more (e.g. 2,3, 4 or 5) of the groups: sodium hydride, sodium hydroxide, sodium carbonate, potassium carbonate,Sodium salt andpotassium salt, and may be selected from one or more (e.g., 2,3, 4, or 5) of the following group: sodium hydroxide, sodium carbonate, potassium carbonate,Sodium salt anda potassium salt.

In one embodiment, the sodium hydroxide may be generated in situ from water and sodium hydride.

In one aspect, theThe sodium salt can be sodium methoxide, sodium 2-methyl-2-nonanolate, sodium tert-butoxide, sodium 1-adamantanolate, sodium isopropoxide, sodium ethoxide, sodium terpineolate, sodium 3-ethyl-3-pentanolate, sodium 2-methyl-2-hexanolate, sodium 1, 3-propanediol, sodium glycerolate, sodium pentaerythritol, or sodium 2-methyl-2-pentanolate.

In one aspect, theThe potassium salt can be potassium methoxide, potassium 2-methyl-2-nonanoate, potassium tert-butoxide, potassium 1-adamantanoate, potassium isopropoxide, potassium ethoxide, potassium terpineolate, potassium 3-ethyl-3-pentanolate, potassium 2-methyl-2-hexanoate, potassium 1, 3-propanediol, potassium glycerolate, potassium pentaerythritol or potassium 2-methyl-2-pentanolate.

In one aspect, theThe sodium salt can be prepared fromGenerated in situ with sodium hydride.

In one aspect, theThe potassium salt can be prepared fromGenerated in situ with potassium hydride.

In one embodiment, when the base is sodium hydroxide, the sodium hydroxide can be generated in situ from water and sodium hydride, wherein the amount of the water can be a catalytic amount, and the generated sodium hydroxide reacts to generate water again; the molar amount of sodium hydride may be the same as the molar amount of base. That is, the sodium hydroxide may be added in the form of water and sodium hydride.

In one aspect, when the amount of water can be a catalytic amount, the catalytic amount refers to: the molar ratio of the water to the compound shown as the formula II can be (0.08-0.15): 1, and may be 0.10: 1.

in one embodiment, when the base is sodium hydroxide, the sodium hydroxide may be partially added directly, and partially generated in situ from water and sodium hydride; the water can be generated by directly adding sodium hydroxide to participate in the reaction. That is, the sodium hydroxide may be added in the form of sodium hydroxide and sodium hydride, or may be added in the form of water, sodium hydroxide and sodium hydride.

In one embodiment, when the base isWhen the sodium salt is mentionedThe sodium salt can be prepared fromGenerated in situ with sodium hydride, whereinThe amount of (b) can be a catalytic amount, which results inSodium salt reacts and is regeneratedThe molar amount of sodium hydride may be the same as the molar amount of base. That is, as describedThe sodium salt can be prepared fromAnd sodium hydride.

In one aspect, when saidWhen the amount of (b) can be a catalytic amount, said catalytic amount refers to: saidThe molar ratio of the compound to the compound shown in the formula II can be (0.03-0.3): 1, may be 0.03: 1. 0.05: 1. 0.06: 1. 0.07: 1. 0.123: 1. 0.125: 1. 0.165: 1. 0.25: 1 or 0.3: 1.

in one embodiment, when the base isWhen the sodium salt is mentionedThe sodium salt can be added partially directly and partially fromIn situ generation with sodium hydride; saidCan be added directlySodium salt is generated after the reaction. That is to say that the first and second electrodes,the sodium salt can be prepared fromThe sodium salt and the sodium hydride are added in the form of sodium salt and can also be added in the form ofSodium salt and sodium hydride.

In a certain scheme, the molar ratio of the base to the compound shown in formula II may be (2-4): 1{ e.g., 2:1, 2.5:1 or 4:1}, and may also be (2-2.5): 1.

in one embodiment, the condensation reaction may also be carried out in the presence of an initiator, wherein the initiator is

R^1-IIIs hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

R^2-IIis hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

R^3-IIis hydrogen, C₁～C₁₀Alkyl of (C)₂～C₁₀Alkenyl or C₁～C₁₀Alkoxy group of (a);

or, R²、R³And the carbon atoms to which they are attached form C₆～C₁₀Aryl of (a), C substituted by one or more hydroxy groups₆～C₁₀Aryl of (a), or a 5-to 10-membered heteroAn aryl group; the hetero atom in the heteroaryl is selected from one or more of N, O and S, and the number of the hetero atoms is 1,2 or 3;

R^4-IIis O;

R^5-IIis O.

In one embodiment, when R^1-IIIs C₁～C₁₀When there is an alkyl group, said C₁～C₁₀The alkyl group of (A) may be C₁～C₄The alkyl group of (b) may be a methyl group.

In one embodiment, when R^1-IIIs C₂～C₁₀When said alkenyl is said C₂～C₁₀The alkenyl group of (A) may be C₂～C₅The alkenyl group of (a) may also be 3-methyl-2-buten-1-yl

In one embodiment, when R^1-IIIs C₁～C₁₀Alkoxy of (2), said C₁～C₁₀The alkoxy group of (A) may be C₁～C₄The alkoxy group of (b) may be a methoxy group.

In one embodiment, when R^2-IIIs C₁～C₁₀When there is an alkyl group, said C₁～C₁₀The alkyl group of (A) may be C₁～C₄The alkyl group of (b) may be a methyl group.

In one embodiment, when R^2-IIIs C₂～C₁₀When said alkenyl is said C₂～C₁₀The alkenyl group of (A) may be C₂～C₅The alkenyl group of (a) may also be 3-methyl-2-buten-1-yl

In one embodiment, when R^2-IIIs C₁～C₁₀Alkoxy of (2), said C₁～C₁₀The alkoxy group of (A) may be C₁～C₄The alkoxy group of (b) may be a methoxy group.

In one embodiment, when R^3-IIIs C₁～C₁₀When there is an alkyl group, said C₁～C₁₀The alkyl group of (A) may be C₁～C₄The alkyl group of (b) may be a methyl group.

In one embodiment, when R^3-IIIs C₂～C₁₀When said alkenyl is said C₂～C₁₀The alkenyl group of (A) may be C₂～C₅The alkenyl group of (a) may also be 3-methyl-2-buten-1-yl

In one embodiment, when R^3-IIIs C₁～C₁₀Alkoxy of (2), said C₁～C₁₀The alkoxy group of (A) may be C₁～C₄The alkoxy group of (b) may be a methoxy group.

In one embodiment, when R^2-II、R^3-IIAnd the carbon atoms to which they are attached form C₆～C₁₀Aryl of (2), said C₆～C₁₀The aryl group of (a) may be phenyl.

In one embodiment, when R^2-II、R^3-IIAnd the carbon atoms to which they are attached together form C substituted by one or more hydroxy groups₆～C₁₀Aryl of (2), said C₆～C₁₀The aryl group of (a) may be phenyl.

In one embodiment, R is^1-IIAnd said R¹The same; said R^2-IIAnd said R²The same; said R^3-IIAnd said R³The same is true.

In one aspect, theCan be 1, 4-hydroquinone.

In a certain scheme, the molar ratio of the initiator to the compound shown in the formula II can be (0.005-1): 1{ e.g., 0.01:1, 0.025:1, 0.05:1, 0.075:1, 0.10:1, 0.15:1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1, or 0.8:1}, and may be (0.025 to 0.10): 1, can also be (0.05-0.10): 1.

in one embodiment, the initiatorCan be generated in situ by the compound shown as the formula II and a reducing agent. That is, the initiator can be generated in situ in the reaction solution by directly adding the reducing agent (but not adding a separate initiator). In other words, the condensation reaction may also be carried out in the presence of a reducing agent.

In one embodiment, the reducing agent is a reducing agent that is conventional in the art for reducing quinone compounds, and may be a reducing agent that is conventional in the art for reducing quinone compoundsR^7-1And R^7-2Independently is C₁～C₄Alkyl group of (1).

In one aspect, the(may be)

In a certain scheme, the molar ratio of the reducing agent to the compound shown in formula II can be (0.005-1): 1{ e.g., 0.01:1, 0.025:1, 0.05:1, 0.075:1, 0.10:1, 0.15:1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1, or 0.8:1}, and may be (0.025 to 0.10): 1, can also be (0.05-0.10): 1.

in a certain scheme, the molar ratio of the compound shown in the formula III to the compound shown in the formula II can be (0.1-2.0): 1{ e.g., 0.2:1, 0.4:1, 0.5:1, 1:1, 1.05:1, 1.65:1, or 1.70:1}, and may be (0.2 to 1.70): 1.

in one embodiment, the condensation reaction may be carried out at a temperature of from 35 ℃ to 100 ℃ (e.g., 50 ℃, 60 ℃, 65 ℃,70 ℃, 75 ℃, 80 ℃, 85 ℃, 90 ℃ or 95 ℃), from 40 ℃ to 100 ℃, or from 70 ℃ to 80 ℃.

The progress of the condensation reaction can be monitored by TLC, HPLC and the like, and those skilled in the art can terminate the reaction according to the scale of the reaction, the degree of conversion of the raw material, the reaction efficiency (i.e., the relationship between the yield and the reaction time), the formation of impurities and the like to obtain the preferred yield and purity.

In one embodiment, the reaction time of the condensation reaction may be 0.1 to 336 hours (e.g., 3 hours, 5 hours, 6 hours, 12 hours, 21 hours, 24 hours, 28 hours, 30 hours, 36 hours, 40 hours, 48 hours, 60 hours, 72 hours, 96 hours, 100 hours, 120 hours, 144 hours, or 168 hours), and may be 5 to 100 hours.

In one embodiment, the post-treatment of the condensation reaction may comprise the steps of: removing solid, and performing column chromatography.

In one embodiment, the method for removing solids may be centrifugation or filtration.

In one embodiment, the condensation reaction may have the following reaction parameters: the condensation reaction is carried out in the presence of protective gas; the condensation reaction is carried out in an organic solvent, the organic solvent is a halogenated aromatic hydrocarbon solvent, and the molar volume ratio of the compound shown as the formula II to the organic solvent is 0.1-0.3 mol/L; the alkali is sodium hydroxide orSodium salt, R^xIs composed ofR^x-2Can be C₁～C₇The molar ratio of the alkali to the compound shown as the formula II is (2-4): 1; the condensation reaction is carried out inIn the presence of a catalyst, saidThe molar ratio of the compound to the compound shown in the formula II is (0.025-0.10): 1; the molar ratio of the compound shown as the formula III to the compound shown as the formula II is (0.2-2.0): 1; the condensation reaction temperature is 40-100 ℃.

In one embodiment, the condensation reaction may have the following reaction parameters: the condensation reaction is carried out in the presence of nitrogen; the condensation reaction is carried out in chlorobenzene or o-dichlorobenzene, and the molar volume ratio of the compound shown as the formula II to the chlorobenzene or o-dichlorobenzene is 0.1-0.2 mol/L; the base isSodium salt, R^xIs composed ofIs tert-butyl, The molar ratio of the alkali to the compound shown as the formula II is (2-2.5): 1; the condensation reaction is also described inIn the presence of a catalyst, saidThe molar ratio of the compound to the compound shown in the formula II is (0.05-0.10): 1; the molar ratio of the compound shown as the formula III to the compound shown as the formula II is (0.2-1.70): 1; the temperature of the condensation reaction is 70-80 ℃.

In one embodiment, the condensation reaction may have the following reaction parameters: the condensation reaction is carried out in the presence of nitrogen; the condensation reaction is carried out in chlorobenzene or o-dichlorobenzene, and the molar volume ratio of the compound shown as the formula II to the chlorobenzene or o-dichlorobenzene is 0.1-0.2 mol/L; the base is sodium hydride andsodium salt, R^xIs composed ofIs tert-butyl,The molar ratio of the alkali to the compound shown as the formula II is (2-2.5): 1; the condensation reaction is also described inIn the presence of a catalyst, saidThe molar ratio of the compound to the compound shown in the formula II is (0.05-0.10): 1; the molar ratio of the compound shown as the formula III to the compound shown as the formula II is (0.2-1.70): 1; the temperature of the condensation reaction is 70-80 ℃.

In one embodiment, the condensation reaction may have the following reaction parameters: the condensation reaction is carried out in the presence of nitrogen; the condensation reaction is carried out in chlorobenzene or o-dichlorobenzene, and the molar volume ratio of the compound shown as the formula II to the chlorobenzene or o-dichlorobenzene is 0.1-0.2 mol/L; the base is sodium hydride andR^xis composed ofIs tert-butyl,The molar ratio of the alkali to the compound shown as the formula II is (2-2.5): 1, theThe molar ratio of the compound to the compound shown in the formula II is (0.03-0.3): 1; the condensation reaction is also described inIn the presence of a catalyst, saidThe molar ratio of the compound to the compound shown in the formula II is (0.05-0.10): 1; the molar ratio of the compound shown as the formula III to the compound shown as the formula II is (0.2-1.70): 1; the temperature of the condensation reaction is 70-80 ℃.

In the present invention, unless otherwise specified, each term has the following meaning:

the term "plurality" means 2,3, 4 or 5.

The term "plurality" means 2,3, 4 or 5.

The term "basic" is defined to follow the bronsted-lowry definition and is the ability of a substance to bind to protons, the stronger the ability to bind to protons, the more basic. The basicity of a substance can be characterized by the pKa value of the conjugate acid of the substance, with the greater the pKa of its conjugate acid, the more basic the substance. The pKa may be measured in Lange's Handbook of Chemistry,13^thEdition, pages 5-93 or J.Am.chem.Soc.1975,97, 7006-. "a substance is more basic than sodium phenate" means: in the same solvent (or reaction system), the pKa of the conjugate acid of the substance is greater than that of phenol. For example, when measured by the above-mentioned literature method (J.Am. chem.Soc.1975,97,7006-7014), the pKa of phenol, which is the conjugate acid of sodium phenolate, is 18.0(Acc.chem.Res.1988,21,456-463) when measured in dimethylsulfoxide at 25 ℃ and, if the pKa of the conjugate acid of a base is greater than 18.0 in dimethylsulfoxide at 25 ℃, the base is considered to be more basic than sodium phenolate, whereas, the base is considered to be less basic than sodium phenolateSodium phenolate.

The term "halogen" refers to elemental fluorine, elemental chlorine, elemental bromine, or elemental iodine.

The term "hydrocarbyl" refers to a group formed by a hydrocarbon losing 1 hydrogen atom.

The term "alkyl" refers to a saturated straight or branched chain hydrocarbon group containing 1 or more carbon atoms. C for alkyl radicals containing n carbon atoms_nIs represented by C_m～C_nMeaning that the alkyl group contains at least m and at most n carbon atoms. Representative saturated straight chain alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, and the like; representative saturated branched alkyl groups include isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl and the like

The term "cycloalkyl" refers to a saturated monocyclic or polycyclic (e.g., spiro, fused, or bridged) alkyl group having from 3 to 10 ring carbon atoms, and also from 3 to 6 ring carbon atoms. Examples of cycloalkyl groups include, but are not limited to: adamantyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

The term "alkoxy" refers to-O- (alkyl), wherein "alkyl" is alkyl as defined above.

The term "alkenyl" refers to an unsaturated straight or branched chain hydrocarbon radical containing one or more double bonds and multiple carbon atoms. Representative linear alkenyl groups include, but are not limited to, ethenyl, propenyl, allyl, and the like.

The term "cycloalkenyl" refers to an unsaturated (but not aromatic), monocyclic or polycyclic (e.g., spiro, fused, or bridged) cyclic hydrocarbon group containing one or more double bonds and multiple carbon atoms. Representative cycloalkenyl groups include, but are not limited to, cyclopentenyl, cyclohexenyl, and the like.

The term "aryl" refers to phenyl or naphthyl.

The term "heteroaryl" refers to an aromatic group containing 1,2 or 3 members independently selected from a 5-6 membered monocyclic or 9-10 membered bicyclic (e.g., fused or bridged) ring of nitrogen, oxygen and sulfur, when bicyclic, at least one ring is aromatic, including but not limited to furyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, imidazolyl, pyrrolyl, pyrazolyl, triazolyl, thiazolyl, isothiazolyl, thiadiazolyl, benzimidazolyl, indolyl, indazolyl, benzothiazolyl, benzisothiazolyl, benzoxazolyl, benzisoxazolyl, quinolinyl, isoquinolinyl, and the like.

The above preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention without departing from the common general knowledge in the art.

The reagents and starting materials used in the present invention are either commercially available or prepared according to published literature.

The positive progress effects of the invention are as follows: (1) the synthesis is carried out by one step by a one-pot method, and separation and purification are not needed in the middle; (2) the raw materials are cheap and easy to obtain; (3) no protective group is used, so that hazardous waste is reduced; (4) no heavy metal reagent is used, and no harmful metal residue exists; (5) no external oxidant is used; (6) no strong lewis acid reagent is used; (7) the reaction condition is simple, and the product selectivity is high.

Detailed Description

The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.

Example 1

A dry 100mL flask was charged with a magnetic stirrer, 1.36g (10mmol, 1 eq.) of 2, 3-dimethyl-p-benzoquinone, 126mg (0.5mmol, 0.05 eq.) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 50mL of dry chlorobenzene, 1.73g (16.5mmol, 1.65 eq.) of 1-chloro-3-methyl-2-butene (isopentenyl chloride), and 237mg (1.5mmol, 0.15 eq.) of 2-methyl-2-nonanol, in that order. After the solid had dissolved, 0.8g of a commercially available 60% sodium hydride-mineral oil mixture (about 0.5 g sodium hydride, about 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round bottom flask, displacing the nitrogen andcontinuously introducing nitrogen bubbles into the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 48 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: column chromatography was performed on the ethyl acetate mixture to obtain 1.69g of 2, 3-dimethyl-5- (3-methyl-2-buten-1-yl) p-benzoquinone in 83% yield. A yellow oily liquid.¹H-NMR(400MHz,CDCl₃)δ(ppm)6.47(d,J＝1.9Hz,1H),5.19–5.10(m,1H),3.11(d,J＝7.3Hz,2H),2.06–1.99(m,6H),1.76(s,3H),1.63(d,J＝1.7Hz,3H).¹³C-NMR(101MHz,CDCl₃)δ(ppm)187.89,187.69,148.02,141.01,140.56,136.03,132.05,118.33,27.59,25.75,17.74,12.39,12.04.

Example 2

In a dry 10mL flask, a magnetic stirrer, 68mg (0.5mmol, 1 equivalent) of 2, 6-dimethyl-p-benzoquinone, 6.3mg (0.025mmol, 0.05 equivalent) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 87mg (0.83mmol, 1.66 equivalent) of 1-chloro-3-methyl-2-butene (isopentenyl chloride), and 23.7mg (0.15mmol, 0.3 equivalent) of 2-methyl-2-nonanol were sequentially added. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 48 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: the ethyl acetate mixture was subjected to column chromatography to give 97mg of 2, 6-dimethyl-3- (3-methyl-2-buten-1-yl) p-benzoquinone in a yield of 95%. A yellow oily liquid.¹H-NMR(400MHz,CDCl₃)δ(ppm)6.55(d,J＝2.2Hz,1H),4.94(t,J＝7.1Hz,1H),3.18(d,J＝7.0Hz,2H),2.06–2.01(m,6H),1.74(s,3H),1.67(s,3H).¹³C-NMR(126MHz,CDCl₃)δ(ppm)188.46,187.19,145.23,143.42,140.71,133.79,133.12,119.23,25.71,25.40,17.97,15.88,12.18.HRMS(ESI)calcd.For C₁₃H₁₇O₂ ⁺:205.1223.Found:205.1221(M-H⁺)。

Examples 3 to 31

Examples 3 to 31 were formed by changing the kinds and amounts of the raw materials in example 2. The material types and the dosage are specifically changed as shown in the following table:

note that: the equivalent weights in the above table are 1 equivalent of 2, 6-dimethyl-p-benzoquinone. HE ═ 2, 6-dimethyl-3, 5-bis (ethoxyacyl) -1, 4-dihydropyridine; HQ ═ 1, 4-hydroquinone.

K₂CO₃Has a pKa of 10.25, slightly higher than that of sodium phenolate (9.98).

In example 10, the yield was 56% based on the amount of sodium tert-butoxide added; in example 11, the yield was 47% based on the amount of sodium tert-butoxide added.

Example 32

A dry 10mL flask was charged with a magnetic stirrer, followed by 68mg (0.5mmol, 1 eq.) of 2, 6-dimethyl-p-benzoquinone, 6.3mg (0.025mmol, 0.05 eq.) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 143mg (0.83mmol, 1.66 eq.) of 1-chloro-3, 7-dimethyl-2, 6-dioctylene (geranylchloride), and 11.9mg (0.15mmol, 0.15 eq.) of 2-methyl-2-nonanol. After the solid had dissolved, 40mg of commercially available solid was added to the reaction flaskA60% sodium hydride-mineral oil mixture (about 24mg sodium hydride, 2 equivalents) was then connected to a round bottom flask with an air condenser to displace the nitrogen and keep bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 36 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: the ethyl acetate mixture was subjected to column chromatography to give 115.5mg of 2, 6-dimethyl-3- (3, 7-dimethyl-2, 6-diocten-1-yl) p-benzoquinone in 85% yield. A yellow oily liquid.¹H NMR(400MHz,CDCl₃)δ(ppm)6.55(q,J＝1.6Hz,1H),5.07–4.99(m,1H),4.94(tq,J＝7.0,1.3Hz,1H),3.19(d,J＝6.9Hz,2H),2.03(d,J＝1.7Hz,8H),1.97(dd,J＝8.9,6.2Hz,2H),1.73(d,J＝1.4Hz,3H),1.65(d,J＝1.5Hz,3H).¹³C NMR(101MHz,CDCl₃)δ(ppm)188.47,187.15,145.23,143.53,140.80,137.32,133.12,131.54,124.02,119.17,39.67,26.53,25.68,25.25,17.68,16.30,15.89,12.18.HRMS(ESI)calcd.For C₁₈H₂₅O₂ ⁺:273.1849.Found:273.1844(M-H⁺)

Example 33

In a dry 10mL flask, a magnetic stirrer, 68mg (0.5mmol, 1 equivalent) of 2, 6-dimethyl-p-benzoquinone, 6.3mg (0.025mmol, 0.05 equivalent) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 200mg (0.83mmol, 1.66 equivalent) of 1-chloro-3, 7, 11-trimethyl-2, 6, 10-dodecatriene (farnesyl chloride), and 11.9mg (0.15mmol, 0.15 equivalent) of 2-methyl-2-nonanol were added in this order. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 36 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: performing column chromatography on the ethyl acetate mixture to obtain 2, 6-dimethyl133.5mg of (E) -3- (3,7, 11-trimethyl-2, 6, 10-dodecatrien-1-yl) p-benzoquinone, yield 78%. A yellow oily liquid.¹H-NMR(400MHz,CDCl₃)δ(ppm)6.47(q,J＝1.6Hz,1H),5.07–4.93(m,2H),4.87(t,J＝14.8Hz,1H),3.11(d,J＝7.0Hz,2H),2.03–1.93(m,10H),1.91(d,J＝7.6Hz,2H),1.86(dd,J＝9.4,6.2Hz,2H),1.67(d,J＝1.4Hz,3H),1.60(t,J＝2.7Hz,3H),1.51(s,3H),1.50(s,3H).¹³C-NMR(101MHz,CDCl₃)δ(ppm)188.44,187.14,145.22,143.51,140.76,137.36,135.18,133.11,131.29,124.33,123.85,119.15,39.70,39.67,26.75,26.43,25.70,25.27,17.67,16.32,16.02,15.87,12.19.

Example 34

In a dry 10mL flask, a magnetic stirrer, 68mg (0.5mmol, 1 equivalent) of 2, 6-dimethyl-p-benzoquinone, 6.3mg (0.025mmol, 0.05 equivalent) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, (2E,7R,11R) -1-chloro-3, 7,11, 15-tetramethyl-2-hexadecene (phytyl chloride), 259mg (0.83mmol, 1.66 equivalent) of 2-methyl-2-nonanol, were added in this order. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 60 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: column chromatography was performed on the ethyl acetate mixture to give 109.5mg of 3, 5-dimethyl-2- ((2E,7R,11R) -3,7,11, 15-tetramethyl-2-hexadecen-1-yl) p-benzoquinone in 53% yield. A yellow oily liquid.¹H-NMR(400MHz,CDCl₃)δ(ppm)6.55(d,J＝1.8Hz,1H),4.98–4.89(m,1H),3.19(d,J＝7.0Hz,2H),2.03(d,J＝2.5Hz,6H),1.95–1.89(m,2H),1.72(s,3H),1.67–1.62(m,1H),1.52(dt,J＝13.3,6.6Hz,1H),1.33(ddt,J＝24.5,9.1,4.7Hz,5H),1.28–1.17(m,6H),1.14(ddd,J＝9.0,5.7,1.9Hz,3H),1.05(ddt,J＝18.0,10.3,7.7Hz,3H),0.86(d,J＝6.7Hz,6H),0.83(t,J＝6.3Hz,6H).¹³C-NMR(126MHz,CDCl₃)δ(ppm)188.45,187.15,145.20,143.56,140.74,137.78,133.12,118.85,40.00,39.38,37.43,37.39,37.30,36.64,32.79,32.65,27.98,25.28,25.26,24.80,24.47,22.73,22.63,19.75,19.72,16.22,15.88,12.20.

Example 35

A dry 10mL flask was charged with a magnetic stirrer, followed by 68mg (0.5mmol, 1 equivalent) of 2, 6-dimethyl-p-benzoquinone, 6.3mg (0.025mmol, 0.05 equivalent) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 100mg (0.83mmol, 1.66 equivalents) of allyl bromide, and 23.7mg (0.15mmol, 0.3 equivalent) of 2-methyl-2-nonanol. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 48 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: the ethyl acetate mixture was subjected to column chromatography to give 28mg of 3, 5-dimethyl-2-allylbenzoquinone in 32% yield. A yellow oily liquid.¹H-NMR(400MHz,CDCl₃)δ(ppm)6.57(s,1H),5.81-5.63(m,2H),5.09(d,J＝9.3Hz,1H),3.24(d,J＝6.6Hz,2H),2.05(s,6H).

Example 36

A dry 10mL flask was charged with a magnetic stirrer, 68mg (0.5mmol, 1 eq.) of 2, 6-dimethyl-p-benzoquinone, 6.3mg (0.025mmol, 0.05 eq.) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 112mg (0.83mmol, 1.66 eq.) of trans-1-bromo-2-butene (crotyl bromide), and 2-Methyl-2-nonanol 23.7mg (0.15mmol, 0.3 equiv.). After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 48 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: column chromatography was performed on the ethyl acetate mixture to give 46.5mg of 3, 5-dimethyl-2- (2-buten-1-yl) p-benzoquinone in 49% yield. A yellow oily liquid.¹H-NMR(400MHz,CDCl₃)δ(ppm)6.55(q,J＝1.7Hz,1H),5.55–5.42(m,1H),5.41–5.29(m,1H),3.16(d,J＝6.3Hz,2H),2.04(s,6H),1.62(dt,J＝6.4,1.5Hz,3H).¹³C-NMR(101MHz,CDCl₃)δ(ppm)188.37,187.04,145.33,142.45,141.12,133.09,127.36,125.71,29.13,17.87,15.90,12.05.

Example 37

A dry 10mL flask was charged with a magnetic stirrer, followed by 68mg (0.5mmol, 1 eq.) of 2, 6-dimethyl-p-benzoquinone, 6.3mg (0.025mmol, 0.05 eq.) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 134.5mg (0.83mmol, 1.66 eq.) of cis-1-bromo-2-hexene, and 23.7mg (0.15mmol, 0.3 eq.) of 2-methyl-2-nonanol. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 48 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: the ethyl acetate mixture was subjected to column chromatography to give 30mg of 3, 5-dimethyl-2- (cis-2-hexen-1-yl) p-benzoquinone in 28% yield. A yellow oily liquid.¹H-NMR(500MHz,CDCl₃)δ(ppm)6.55(q,J＝1.7Hz,1H),5.50–5.40(m,1H),5.19(dtt,J＝10.6,7.1,1.7Hz,1H),3.24(d,J＝8.6Hz,2H),2.15(qd,J＝7.4,1.7Hz,2H),2.05(s,3H),2.04–2.03(m,3H),1.42(h,J＝7.4Hz,2H),0.94(t,J＝7.4Hz,3H).

Example 38

In a dry 10mL flask, a magnetic stirrer, 68mg (0.5mmol, 1 equivalent) of 2, 6-dimethyl-p-benzoquinone, 6.3mg (0.025mmol, 0.05 equivalent) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 125.5mg (0.83mmol, 1.66 equivalent) of trans-1-chloro-3-phenyl-2-propene (cinnamyl chloride), and 23.7mg (0.15mmol, 0.3 equivalent) of 2-methyl-2-nonanol were added in this order. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 48 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: column chromatography was performed on the ethyl acetate mixture to give 114.5mg of 3, 5-dimethyl-2- (trans-3-phenyl-2-propen-1-yl) p-benzoquinone in 91% yield. A yellow oily liquid.¹H-NMR(400MHz,CDCl₃)δ(ppm)7.34–7.23(m,4H),7.26–7.15(m,1H),6.59(q,J＝1.6Hz,1H),6.42(dt,J＝15.8,1.6Hz,1H),6.11(dt,J＝15.9,6.7Hz,1H),3.39(dd,J＝6.8,1.6Hz,2H),2.10(s,3H),2.05(d,J＝1.7Hz,3H).¹³C-NMR(101MHz,CDCl₃)δ(ppm)188.24,186.93,145.52,141.75,141.62,137.03,133.12,131.90,128.52,127.38,126.11,124.91,29.54,15.95,12.25.

Example 39

A dry 10mL flask was charged with a magnetic stirrer, 68mg (0.5mmol, 1 equivalent) of 2, 6-dimethyl-p-benzoquinone, and 2, 6-dimethyl-benzoquinone in that order6.3mg (0.025mmol, 0.05 equiv.) of 3, 5-bis (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 132mg (0.83mmol, 1.66 equiv.) of 1-bromo-2-cyclohexene, 23.7mg (0.15mmol, 0.3 equiv.) of 2-methyl-2-nonanol. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 48 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: the ethyl acetate mixture was subjected to column chromatography to give 51mg of 3, 5-dimethyl-2- (2-cyclohexen-1-yl) p-benzoquinone in 47% yield. A yellow oily liquid.¹H-NMR(400MHz,CDCl₃)δ(ppm)6.55(q,J＝1.6Hz,1H),5.83–5.75(m,1H),5.51(dp,J＝10.1,2.0Hz,1H),3.88(ddt,J＝8.3,5.8,2.8Hz,1H),2.11(td,J＝4.0,1.8Hz,1H),2.09(s,4H),2.03(d,J＝1.6Hz,3H),1.88(dt,J＝12.9,3.7Hz,1H),1.79(dtd,J＝11.3,4.1,2.3Hz,1H),1.74–1.62(m,1H),1.62–1.51(m,1H).¹³C-NMR(126MHz,CDCl₃)δ(ppm)188.84,187.04,146.79,145.11,142.01,133.41,129.10,127.06,34.18,27.79,24.53,22.68,15.80,12.51.

Example 40

In a dry 10mL flask, a magnetic stirrer, 102.5mg (0.5mmol, 1 equivalent) of 3, 5-dimethyl-2- (3-methyl-2-buten-1-yl) p-benzoquinone, 6.3mg (0.025mmol, 0.05 equivalent) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 125.5mg (0.83mmol, 1.66 equivalent) of trans-1-chloro-3-phenyl-2-propene (cinnamyl chloride), and 23.7mg (0.15mmol, 0.3 equivalent) of 2-methyl-2-nonanol were added in that order. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. Heating the flask to 80 ℃, and stirring for reactionFor 36 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: the ethyl acetate mixture is subjected to column chromatography to obtain 110.5mg of 3, 5-dimethyl-2-trans-cinnamyl-6-isopentenyl p-benzoquinone with the yield of 69 percent. A yellow oily liquid.¹H-NMR(400MHz,CDCl₃)δ(ppm)7.36–7.25(m,4H),7.21–7.17(m,1H),6.44–6.37(m,1H),6.13(dt,J＝15.8,6.8Hz,1H),4.98–4.91(m,1H),3.40(dd,J＝6.7,1.6Hz,2H),3.21(d,J＝7.1Hz,2H),2.08(s,3H),2.04(s,3H),1.76–1.74(m,3H),1.67(d,J＝1.5Hz,3H).

EXAMPLE 41

In a dry 10mL flask, a magnetic stirrer, 68mg (0.5mmol, 1 equivalent) of 2, 3-dimethyl-p-benzoquinone, 6.3mg (0.025mmol, 0.05 equivalent) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 341mg (0.52mmol, 1.05 equivalent) of all E-1-chloro-3, 7,11,15,19,23,27,31, 35-nonamethyl-2, 6,10,14,18,22,26,30, 34-trihexadecanonaene (solaninyl chloride), and 23.7mg (0.15mmol, 0.3 equivalent) of 2-methyl-2-nonanol were sequentially added. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 36 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: the ethyl acetate mixture was subjected to column chromatography to give plastoquinone 179.8mg, 48% yield. A yellow oily liquid.¹H-NMR(400MHz,CDCl₃)δ(ppm)6.49–6.45(m,1H),5.11(t,J＝7.2Hz,9H),3.12(d,J＝7.2Hz,2H),2.06(t,J＝7.2Hz,16H),2.03(s,3H),2.01(s,3H),1.98(dd,J＝9.9,5.5Hz,16H),1.68(s,6H),1.62(s,3H),1.60(s,21H).

Example 42

In a dry 10mL flask, a magnetic stirrer, 75mg (0.5mmol, 1 equivalent) of 2,3, 5-trimethyl-p-benzoquinone, 12.6mg (0.05mmol, 0.1 equivalent) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 259mg (0.83mmol, 1.66 equivalent) of (2E,7R,11R) -1-chloro-3, 7,11, 15-tetramethyl-2-hexadecene (chlorophyllin-yl chloride), and 23.8mg (0.15mmol, 0.3 equivalent) of 2-methyl-2-nonanol were sequentially added. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction was stirred for 100 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: the ethyl acetate mixture was subjected to column chromatography to give 134.5mg of 2,3, 5-trimethyl-6- ((2E,7R,11R) -3,7,11, 15-tetramethyl-2-hexadecen-1-yl) p-benzoquinone in 63% yield. Brown oily liquid.¹H-NMR(500MHz,CDCl₃)δ(ppm)4.94(t,J＝7.0Hz,1H),3.20(d,J＝6.9Hz,2H),2.02(s,3H),2.01(s,6H),1.92(td,J＝7.4,3.8Hz,2H),1.73(s,3H),1.64(d,J＝17.4Hz,1H),1.52(hept,J＝6.7Hz,1H),1.43(s,1H),1.40–1.32(m,2H),1.31–1.18(m,10H),1.18–1.09(m,2H),1.09–1.00(m,2H),0.86(d,J＝6.7Hz,6H),0.83(t,J＝6.3Hz,6H).¹³C-NMR(126MHz,CDCl₃)δ(ppm)187.95,187.02,143.24,140.37,140.32,140.25,137.51,119.20,40.02,39.38,37.43,37.39,37.30,36.65,32.79,32.65,27.98,25.57,25.29,24.80,24.47,22.72,22.63,19.74,19.72,16.21,12.38,12.36,12.17.

Example 43

In a dry 10mL flask, a magnetic stir bar, 86mg (0.5mmol, 1 equivalent) of 2-menadione, 6.3mg (0.025 m) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, were added sequentiallymol, 0.05 eq), dry chlorobenzene 2.5mL, 87mg (0.83mmol, 1.66 eq) of 1-chloro-3-methyl-2-butene (isopentenyl chloride), 13.9mg (0.088mmol, 0.175 eq) of 2-methyl-2-nonanol. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 30 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: the ethyl acetate mixture was subjected to column chromatography to give 58mg of 2-methyl-3-isopentenyl-1, 4-naphthoquinone, yield 48%. A yellow oily liquid.¹H-NMR(500MHz,CDCl₃)δ(ppm)8.08(dt,J＝5.3,2.7Hz,2H),7.68(dd,J＝5.9,3.3Hz,2H),5.01(d,J＝7.2Hz,1H),3.36(d,J＝7.0Hz,2H),2.19(s,3H),1.80(s,3H),1.69(s,3H).¹³C NMR(101MHz,CDCl₃)δ(ppm)185.50,184.58,146.08,143.30,133.98,133.35,133.30,132.19,132.15,126.31,126.20,119.21,26.15,25.75,18.07,12.68.

Examples 44 to 45

Examples 44 to 45 were formed by changing the kinds and amounts of the respective raw materials in example 43. The material types and the dosage are specifically changed as shown in the following table:

example 46

In a dry 10mL flask, a magnetic stirrer, 86mg (0.5mmol, 1 equivalent) of 2-menadione, 6.3mg (0.025mmol, 0.05 equivalent) of 2, 6-dimethyl-3, 5-di (ethoxycarbonyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, (2E,7R,11R) -1-chloro-3, 7,11, 15-tetramethyl-2-hexadecene (chlorophyllin chloride) 259mg (0.83mmol, 1.66 equivalent), 11.9mg (0.075mmol, 0.15 equivalent) of 2-methyl-2-nonanol were added in this order. Until the solid is dissolvedThereafter, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen gas and continuously bubbling nitrogen gas through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 120 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: column chromatography was performed on the ethyl acetate mixture to give 166mg of 2-methyl-3- (3,7,11, 15-tetramethyl-2-hexadecen-1-yl) -1, 4-naphthoquinone (vitamin K1) in 82% yield. A yellow oily liquid.¹H-NMR(500MHz,CDCl₃)δ(ppm)8.07(dq,J＝7.0,4.0,3.5Hz,2H),7.68(dd,J＝5.8,3.2Hz,2H),5.01(t,J＝6.9Hz,1H),3.37(d,J＝6.9Hz,2H),2.19(s,3H),1.99–1.90(m,2H),1.78(s,3H),1.66(d,J＝21.1Hz,1H),1.55–1.48(m,1H),1.42(s,1H),1.34(tt,J＝10.6,4.9Hz,2H),1.30–1.17(m,10H),1.17–1.08(m,2H),1.03(m,2H),0.86(d,J＝6.6Hz,6H),0.82(dd,J＝6.6,3.9Hz,6H).¹³C-NMR(126MHz,CDCl₃)δ(ppm)185.47,184.54,146.22,146.21,143.34,137.96,133.33,133.27,132.21,132.16,126.31,126.19,118.82,40.04,39.38,37.42,37.38,37.30,36.65,32.78,32.65,27.98,26.01,25.29,24.82,24.80,24.46,22.73,22.64,19.74,19.72,16.32,12.70.

Example 47

Example 47 was formed by changing the kinds and amounts of the respective raw materials in example 46. The material types and the dosage are specifically changed as shown in the following table:

examples	Substitute for 2-methyl-2-nonanol, and equivalent of said substitute	Time/h	Yield/%)
				47	2-methyl-2-pentanol, 0.1	65	71

Example 48

In a dry 10mL flask, a magnetic stirrer, 86mg (0.5mmol, 1 equivalent), 6.3mg (0.025mmol, 0.05 equivalent) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 139mg (0.2mmol, 0.4 equivalent) of all E-1-bromo-3, 7,11,15,19,23,27,31, 35-nonamethyl-2, 6,10,14,18,22,26,30, 34-trihexadecanonaene (solanesol bromide), 11.9mg (0.075mmol, 0.15 equivalent) of 2-methyl-2-nonanol were added sequentially. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 36 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: the ethyl acetate mixture is subjected to column chromatography to obtain the vitamin K2-MK9142.5mg with 91 percent yield (calculated by solanesol bromide). Yellow solid.¹H-NMR(500MHz,CDCl₃)δ(ppm)8.07(dq,J＝6.9,4.1,3.5Hz,2H),7.67(dd,J＝5.8,3.3Hz,2H),5.14–4.94(m,9H),3.37(d,J＝6.9Hz,2H),2.19(d,J＝2.5Hz,3H),2.06(t,J＝7.5Hz,16H),2.02–1.95(m,16H),1.79(s,3H),1.68(s,3H),1.60(s,21H),1.56(s,3H)

Example 49

In a dry 10mL flask, a magnetic stirrer, 91mg (0.5mmol, 1 eq.) of 2, 3-dimethoxy-5-methyl-p-benzoquinone, 12.6mg (0.05mmol, 0.1 eq.) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 123.7mg (0.83mmol, 1.66 eq.) of 1-bromo-3-methyl-2-butene (isopentenyl bromide), and 39.7mg (0.25mmol, 0.5 eq.) of 2-methyl-2-nonanol were added in that order. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 21 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: column chromatography was performed on the ethyl acetate mixture to give 77.6mg of 2, 3-dimethoxy-5-methyl-6- (3-methyl-2-buten-1-yl) p-benzoquinone in 62% yield. An orange oily liquid.¹H-NMR(400MHz,CDCl₃)δ(ppm)4.94(t,J＝7.3Hz,1H),4.00(s,3H),3.98(s,3H),3.17(d,J＝7.1Hz,2H),2.02(s,3H),1.74(s,3H),1.68(s,3H).

Example 50

In a dry 10mL flask, a magnetic stirrer, 91mg (0.5mmol, 1 equivalent) of 2, 3-dimethoxy-5-methyl-p-benzoquinone, 12.6mg (0.05mmol, 0.1 equivalent) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry o-dichlorobenzene, 162mg (0.25mmol, 0.5 equivalent) of all-E-formula-1-chloro-3, 7,11,15,19,23,27,31, 35-nonamethyl-2, 6,10,14,18,22,26,30, 34-trihexadecanonaene (solaninyl chloride), and 23.8mg (0.15mmol, 0.3 equivalent) of 2-methyl-2-nonanol were added sequentially. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. Heating the flask to 100 ℃, and stirring for reactionFor 42 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: column chromatography of the ethyl acetate mixture gave 115mg of coenzyme Q9(CoQ9) in 58% yield (calculated as solanyl chloride). Yellow solid.¹H-NMR(500MHz,CDCl₃)δ(ppm)5.11(m,8H),4.94(d,J＝7.8Hz,1H),3.99(d,J＝2.5Hz,3H),3.98(s,3H),3.18(d,J＝6.9Hz,2H),2.06(t,J＝7.5Hz,16H),2.01(s,3H),1.99(t,J＝7.4Hz,16H),1.74(s,3H),1.68(s,3H),1.62(s,3H),1.60(s,21H).

Example 51

A dry 10mL flask was charged with a magnetic stir bar, in that order, 61mg (0.5mmol, 1 equivalent) of 2-methyl-p-benzoquinone, 6.3mg (0.025mmol, 0.05 equivalent) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 87mg (0.83mmol, 1.66 equivalent) of 1-chloro-3-methyl-2-butene (isopentenyl chloride), and 11.9mg (0.075mmol, 0.15 equivalent) of 2-methyl-2-nonanol. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 24 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: the ethyl acetate mixture was subjected to column chromatography to give 74.2mg of 2-methyl-6- (3-methyl-2-buten-1-yl) p-benzoquinone in 78% yield. A yellow oily liquid.¹H-NMR(500MHz,CDCl₃)δ(ppm)6.59(q,J＝1.7Hz,2H),5.18–5.11(m,1H),3.10(d,J＝7.6Hz,2H),2.03(d,J＝1.6Hz,3H),1.76(s,3H),1.63(s,3H).

Example 52

In a dry 10mL flask, magnetic force was added sequentiallyStirring bar, 69mg (0.5mmol, 1 eq.) of 2-methoxy-p-benzoquinone, 6.3mg (0.025mmol, 0.05 eq.) of 2, 6-dimethyl-3, 5-di (ethoxycarbonyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 87mg (0.83mmol, 1.66 eq.) of 1-chloro-3-methyl-2-butene (isopentenyl chloride), and 23.8mg (0.15mmol, 0.3 eq.) of 2-methyl-2-nonanol. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 36 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: the ethyl acetate mixture was subjected to column chromatography to give 70.1mg of 2-methoxy-5- (3-methyl-2-buten-1-yl) p-benzoquinone in a yield of 68%. A yellow oily liquid.¹H-NMR(400MHz,CDCl₃)δ(ppm)6.47(d,J＝1.9Hz,1H),5.14(tt,J＝7.1,1.6Hz,1H),3.82(s,3H),3.13(d,J＝7.3Hz,2H),1.78–1.74(m,3H),1.63(s,3H).

Example 53

In a dry 10mL flask, a magnetic stir bar, 87mg (0.5mmol, 1 eq.) of 5-hydroxy-1, 4-naphthoquinone, 6.3mg (0.025mmol, 0.05 eq.) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 87mg (0.83mmol, 1.66 eq.) of 1-chloro-3-methyl-2-butene (isopentenyl chloride), and 1.9mg (0.025mmol, 0.05 eq.) of t-butanol were added in that order. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 48 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: column chromatography was performed on the ethyl acetate mixture to give 49.7mg of 5-hydroxy-2- (3-methyl-2-buten-1-yl) -1, 4-naphthoquinone, yield 41%. Yellow oilAs a liquid.¹H-NMR(400MHz,CDCl₃)δ(ppm)12.08(s,1H),7.60(d,J＝2.7Hz,1H),7.24(d,J＝4.1Hz,2H),6.73(dt,J＝6.0,1.8Hz,1H),5.27–5.16(m,1H),3.26(d,J＝7.3Hz,2H),1.79(s,3H),1.67(s,3H).

Example 54

In a dry 10mL flask, a magnetic stirrer, 54mg (0.5mmol, 1 equivalent) of 1, 4-p-benzoquinone, 6.3mg (0.025mmol, 0.05 equivalent) of 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-dihydropyridine, 2.5mL of dry chlorobenzene, 87mg (0.83mmol, 1.66 equivalent) of 1-chloro-3-methyl-2-butene (isopentenyl chloride), and 11.9mg (0.075mmol, 0.15 equivalent) of 2-methyl-2-nonanol were added in that order. After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 80 ℃ and the reaction stirred for 36 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: column chromatography was performed on the ethyl acetate mixture to give 50.2mg of 2- (3-methyl-2-buten-1-yl) p-benzoquinone, yield 57%. A yellow oily liquid.¹H-NMR(500MHz,CDCl₃)δ(ppm)6.76(d,J＝10.1Hz,1H),6.70(dd,J＝10.1,2.5Hz,1H),6.53(dd,J＝4.1,1.8Hz,1H),5.19-5.10(m,1H),3.11(d,J＝7.3Hz,2H),1.76(s,3H),1.63(s,3H)；¹³C-NMR(126MHz,CDCl₃)δ(ppm)188.11,187.73,148.66,136.87,136.68,136.43,132.44,117.89,27.59,25.88,17.90.

Example 55

In a dry 10mL flask, a magnetic stirrer, 2, 3-dimethoxy-5-methyl-p-benzoquinone 91mg (0.5mmol, 1 eq.), 2, 6-dimethyl-3, 5-di (ethoxyacyl) -1, 4-di (ethoxyacyl) were added in that orderHydropyridine 12.6mg (0.05mmol, 0.1 equiv.), dry o-dichlorobenzene 2.5mL, all-E formula-1-chloro-3, 7,11,15,19,23,27,31,35, 39-decamethyl-2, 6,10,14,18,22,26,30,34, 38-forty carbon decaene 179mg (0.25mmol, 0.5 equiv.), 2-methyl-2-nonanol 23.8mg (0.15mmol, 0.3 equiv.). After the solid had dissolved, 40mg of a commercially available 60% sodium hydride-mineral oil mixture (about 24mg of sodium hydride, 2 equivalents) was added to the reaction flask, followed by attaching an air condenser to the round-bottomed flask, displacing nitrogen and continuously bubbling nitrogen through the reaction system. The flask was heated to 100 ℃ and the reaction stirred for 42 hours. Thereafter, the reaction solution was centrifuged at 10000 rpm for 2 minutes in a centrifuge tube, and the supernatant was taken and washed with petroleum ether: column chromatography was performed on the ethyl acetate mixture to obtain 102mg of coenzyme Q10(CoQ10) in 47% yield (based on 1-chloro-decamethyl-forty-carbon decene). An orange solid.¹H-NMR(400MHz,CDCl₃)δ(ppm)1.55(s,3H),1.60(s,21H),1.68(s,6H),1.74(s,3H),1.93–2.02(m,18H),2.01(s,3H),2.02–2.13(m,18H),3.18(d,J＝7.2Hz,2H),3.98(s,3H),3.99(s,3H),4.94(t,J＝7.1Hz,1H),5.06(t,J＝6.8Hz,1H),5.12(t,J＝6.8Hz,8H)ppm.

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