阅读说明：本技术 一种番茄红素的合成方法 (Method for synthesizing lycopene ) 是由 晏日安 谭奇坤 于 2020-06-23 设计创作，主要内容包括：本发明公开了一种番茄红素的成方法。该方法包括：以假性紫罗兰酮、氯碘甲烷、溴化锂和三甲基硅甲基锂为原料制得2,6,10-三甲基-2,5,9-十一烷三烯-1-醛；将其与四乙基亚甲基二磷酸酯反应得到3,7,11-三甲基-1,4,6,10-四烯十二烷基膦酸二乙酯；3,7,11-三甲基-1,4,6,10-四烯十二烷基膦酸二乙酯与2,7-二甲基-2,4,6-辛三烯二醛反应得到番茄红素粗品。本发明解决了目前番茄红素的合成中容易造成副产物不易分离的问题,以一种全新的方法制备番茄红素合成过程的中间体,三步反应合成番茄红素,合成工艺过程简单,操作方便,生产过程绿色环保,成本相对低廉,易于实现工业化。(The invention discloses a method for preparing lycopene. The method comprises the following steps: preparing 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde by using pseudo ionone, chloroiodomethane, lithium bromide and trimethyl silyl lithium as raw materials; reacting the diethyl ester with tetraethyl methylene diphosphate to obtain 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate; reacting 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate with 2, 7-dimethyl-2, 4, 6-octatrienedial to obtain a lycopene crude product. The invention solves the problem that byproducts are not easy to separate in the synthesis of the lycopene at present, prepares the intermediate of the synthesis process of the lycopene by a brand new method, synthesizes the lycopene by three-step reaction, has simple synthesis process, convenient operation, green and environment-friendly production process, relatively low cost and easy realization of industrialization.)

1. A synthesis method of lycopene is characterized by comprising the following steps:

(1) pseudo ionone, chloroiodomethane, lithium bromide and trimethyl silyl lithium are taken as raw materials, tetrahydrofuran or/and toluene are taken as solvents, low-temperature reaction is carried out, and then high-temperature reaction is carried out, so as to obtain 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde;

(2) tetraethyl methylene diphosphate reacts with 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde in a solvent under the action of an alkaline catalyst to obtain 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate;

(3) reacting 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate with 2, 7-dimethyl-2, 4, 6-octatrienedial in a solvent under the action of an alkaline catalyst, recrystallizing a product after reaction to obtain a lycopene crude product, and heating the lycopene crude product in ethanol and carrying out condensation reflux reaction to obtain the lycopene.

2. A method of synthesizing lycopene according to claim 1, wherein in the step (1):

the molar ratio of the pseudo ionone, the chloroiodomethane, the lithium bromide and the trimethyl silyl lithium is 1: 1: 1: 1-1: 4: 4: 4;

the temperature of the low-temperature reaction is-80 ℃ to-30 ℃;

the low-temperature reaction time is 0.5-4 h;

the temperature of the temperature raising reaction is 0-35 ℃;

the reaction time for raising the temperature is 6-18 h.

3. A method of synthesizing lycopene according to claim 1, wherein in the step (1):

the molar ratio of the pseudo ionone, the chloroiodomethane, the lithium bromide and the trimethyl silyl lithium is 1: 3: 3: 3;

the temperature of the low-temperature reaction is-78 ℃;

the time of the low-temperature reaction is 1 h;

the temperature of the reaction at the elevated temperature is 25 ℃;

the reaction time is 12 hours when the temperature is increased;

trimethyl silyllithium is added into pseudo ionone, chloroiodomethane and lithium bromide at the speed of 0.5mL/min for reaction.

4. A method of synthesizing lycopene according to claim 1, wherein in the step (2):

the alkaline catalyst is at least one of sodium hydride, sodium ethoxide and potassium tert-butoxide;

the mole ratio of the 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde, tetraethyl methylene diphosphate and alkaline catalyst is 1: 0.8: 0.8-1: 3: 3;

the reaction time is 0.5-8 h;

the reaction temperature is 0-55 ℃;

the solvent is at least one of toluene, tetrahydrofuran and N, N-dimethylformamide.

5. A method of synthesizing lycopene according to claim 1, wherein in the step (2):

the alkaline catalyst is sodium hydride;

the mole ratio of the 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde, tetraethyl methylene diphosphate and alkaline catalyst is 1: 1.2: 1.2;

the reaction time is 2 hours;

the reaction temperature is 35 ℃;

the tetraethyl methylene diphosphate is added to a solvent containing a basic catalyst at a rate of 1mL/min, followed by addition of 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde at a rate of 1 mL/min; controlling the temperature of the reaction system to be 0 ℃ when adding the reagent;

the solvent is toluene.

6. A method of synthesizing lycopene according to claim 1, wherein in the step (3):

the alkaline catalyst is at least one of sodium hydride, sodium ethoxide and potassium tert-butoxide;

the molar ratio of the 2, 7-dimethyl-2, 4, 6-octatrienedial to the 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate to the alkaline catalyst is 1: 0.8: 0.8-1: 5: 5;

the reaction time is 0.5-8 h;

the reaction temperature is 0-55 ℃;

the solvent is at least one of toluene, tetrahydrofuran and dimethyl sulfoxide;

the recrystallization solvent is one of dichloromethane, chloroform and petroleum ether.

7. A method of synthesizing lycopene according to claim 1, wherein in the step (3):

the alkaline catalyst is potassium tert-butoxide;

the molar ratio of the 2, 7-dimethyl-2, 4, 6-octatrienedial to the 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate to the alkaline catalyst is 1: 2.2: 2.6;

the reaction time is 3 hours;

the reaction temperature is 30 ℃;

adding the 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate into a solvent containing a basic catalyst at the speed of 1mL/min, and then adding 2, 7-dimethyl-2, 4, 6-octatrienedial at the speed of 1 mL/min; controlling the temperature of a reaction system to be-30 ℃ when adding a reagent;

the solvent is a mixed solution of tetrahydrofuran and dimethyl sulfoxide with the volume ratio of 8: 1;

the recrystallization solvent is dichloromethane.

8. A method of synthesis of lycopene according to claim 1, characterized in that:

the reflux reaction time in the step (3) is 0.5-4 h, and the reflux reaction temperature is 50-100 ℃.

9. A method of synthesis of lycopene according to claim 1, characterized in that:

the reflux reaction time in the step (3) is 1 h; the temperature of the reflux reaction was 75 ℃.

10. A method of synthesis of lycopene according to claim 1, characterized by comprising the following steps:

(1) pseudo ionone, chloroiodomethane, lithium bromide and trimethyl silyl lithium are used as raw materials, tetrahydrofuran is used as a solvent, the raw materials are firstly reacted for 1 hour at minus 78 ℃, and then the temperature is raised to 25 ℃ for 12 hours to obtain 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde;

(2) tetraethyl methylene diphosphate reacts with 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde in a solvent under the action of an alkaline catalyst sodium hydride at the temperature of 35 ℃ for 2 hours to obtain 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate;

(3) reacting 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate with 2, 7-dimethyl-2, 4, 6-octatrienedial in a solvent at 30 ℃ for 3h under the condition of a basic catalyst of potassium tert-butoxide, recrystallizing the reacted product to obtain a lycopene crude product, and heating the lycopene crude product in ethanol and carrying out condensation reflux reaction to obtain the lycopene.

Technical Field

The invention belongs to the field of food additives, and particularly relates to a synthesis method of a food colorant lycopene.

Background

Lycopene is a natural and safe food colorant, and is a nutrient enhancer with excellent performance. Lycopene not only has bright color and strong tinting strength, but also has excellent physiological function. With the continuous exploration on the physiological activity of lycopene, the application prospect of lycopene in the fields of food, medicine, cosmetics and the like is wider and wider. It is also becoming more and more important how to efficiently and inexpensively prepare lycopene.

At present, there are three main ways of producing lycopene: chemical synthesisMethods, natural extraction methods and microbial fermentation methods. The natural extraction method has high cost and low yield. The intermediate product of the microbial fermentation method during production can affect the separation purity of lycopene, and the related technology needs to be further mature. The chemical synthesis of lycopene has the characteristics of high yield and low cost, and has higher economic benefit. And the chemically synthesized lycopene can be used as a food colorant to be added into various foods (modified milk, flavored fermented milk, candies, instant grains, baked foods, solid soup bases, semi-solid compound seasonings, beverages and jellies) specified in the GB 2760-2014 food safety national standard food additive use standard. At present, the chemical synthesis route of lycopene used in industry uses pseudoionone as raw material and carries out nucleophilic addition, selective hydrogenation and SN₁Substitution salifying reaction to generate triphenyl (3,7, 11-trimethyl-2, 4,6, 10-tetraene dodecyl) -phosphine bromide, and finally carrying out Wittig reaction with 2, 7-dimethyl-2, 4, 6-octatriene-1, 8-dialdehyde to obtain the lycopene. Triphenylphosphine oxide which is not easy to separate and recover is generated in the process of synthesizing the lycopene by the Wittig method, and a byproduct phosphonate is easy to dissolve in water and separate when the lycopene is synthesized by the Wittig-Horner method. The invention provides a synthesis method of lycopene, aiming at meeting the higher development requirements of the food industry in the future and enabling people to obtain cheaper green and safe lycopene, and under the background of a feasible scheme that the industry needs easy industrialization, relatively cheap production cost and considerable yield of final products.

Disclosure of Invention

In order to overcome the disadvantages and shortcomings of the prior art, the invention aims to provide a preparation method of lycopene.

The purpose of the invention is realized by the following scheme:

lycopene of formula C₄₀H₅₆The relative molecular weight is 536.85, the deep red needle crystal is dissolved in chloroform, benzene and grease, is insoluble in water, is unstable to light and oxygen, and turns brown when meeting iron.

The structural formula of the lycopene is as follows:

the synthesis method of the lycopene comprises a preparation method of alpha-substituted-alpha, beta-unsaturated aldehyde and a Wittig-Horner reaction, and specifically comprises the following steps:

(1) pseudo ionone (compound I), chloroiodomethane, lithium bromide and trimethyl silyl lithium are used as raw materials, tetrahydrofuran or/and toluene are used as solvents, low-temperature reaction is carried out, and then temperature rise reaction is carried out, so that 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde (compound II) is obtained;

(2) tetraethyl methylene diphosphate (compound III) reacts with 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde (compound II) in a solvent under the action of an alkaline catalyst to obtain 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate (compound IV);

(3) reacting diethyl 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl phosphonate (compound IV) with 2, 7-dimethyl-2, 4, 6-octatrienedial (compound V) in a solvent under the action of an alkaline catalyst, recrystallizing a product after reaction to obtain a lycopene crude product, heating the lycopene crude product in ethanol, and carrying out condensation reflux reaction to obtain the lycopene (compound VI).

The molar ratio of the pseudo ionone, the chloroiodomethane, the lithium bromide and the trimethyl silyllithium in the step (1) is 1: 1: 1: 1-1: 4: 4: 4, preferably 1: 3: 3: 3; the temperature of the low-temperature reaction in the step (1) is-80 ℃ to-30 ℃, and is preferably-78 ℃; the low-temperature reaction time in the step (1) is 0.5-4 h, preferably 1 h; the temperature of the temperature-raising reaction in the step (1) is 0-35 ℃, and is preferably 25 ℃; the reaction time for raising the temperature in the step (1) is 6-18 h, preferably 12 h; to avoid too violent reaction, it is preferable to add trimethylsilyllithium to the pseudoionone, chloroiodomethane and lithium bromide at a rate of 0.5 mL/min.

The alkaline catalyst in the step (2) is at least one of sodium hydride, sodium ethoxide and potassium tert-butoxide, preferably sodium hydride; the molar ratio of the 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde, the tetraethyl methylene diphosphate and the basic catalyst in the step (2) is 1: 0.8: 0.8-1: 3: 3, preferably 1: 1.2: 1.2; the reaction time in the step (2) is 0.5-8 h, preferably 2 h; the reaction temperature in the step (2) is 0-55 ℃, and preferably 35 ℃; for good catalytic effect, the tetraethyl methylene diphosphate is preferably added to the solvent containing the basic catalyst at a rate of 1mL/min, and then 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde is added at a rate of 1 mL/min; in order to avoid the reaction from being too violent, the temperature of the reaction system is preferably controlled to be 0 ℃ when the reagent is added; the solvent in the step (2) is at least one of toluene, tetrahydrofuran and N, N-dimethylformamide, and is preferably toluene.

The alkaline catalyst in the step (3) is at least one of sodium hydride, sodium ethoxide and potassium tert-butoxide, preferably potassium tert-butoxide; the molar ratio of the 2, 7-dimethyl-2, 4, 6-octatrienedial, the 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate and the alkaline catalyst in the step (3) is 1: 0.8: 0.8-1: 5: 5, preferably 1: 2.2: 2.6; the reaction time in the step (3) is 0.5-8 h, preferably 3 h; the reaction temperature in the step (3) is 0-55 ℃, and preferably 30 ℃; in order to achieve good catalytic effect, preferably 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate is added into solvent containing alkaline catalyst at the speed of 1mL/min, and then 2, 7-dimethyl-2, 4, 6-octatrienedial is added at the speed of 1 mL/min; in order to avoid too violent reaction, the temperature of the reaction system is preferably controlled to be-30 ℃ when the reagent is added; the solvent in the step (3) is at least one of toluene, tetrahydrofuran and dimethyl sulfoxide, and is preferably a mixed solution of tetrahydrofuran and dimethyl sulfoxide with a volume ratio of 8: 1; the recrystallization solvent in the step (3) is one of dichloromethane, chloroform and petroleum ether, and dichloromethane is preferred.

The reflux reaction time in the step (3) is 0.5-4 h, preferably 1 h; the temperature of the reflux reaction in the step (4) is 50 ℃ to 100 ℃, and preferably 75 ℃.

Preferably, the synthesis method comprises the following steps:

(1) pseudo ionone, chloroiodomethane, lithium bromide and trimethyl silyl lithium are used as raw materials, tetrahydrofuran is used as a solvent, the raw materials are firstly reacted for 1 hour at minus 78 ℃, and then the temperature is raised to 25 ℃ for 12 hours to obtain 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde;

(2) tetraethyl methylene diphosphate reacts with 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde in a solvent under the action of an alkaline catalyst sodium hydride at the temperature of 35 ℃ for 2 hours to obtain 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate;

(3) reacting 3,7, 11-trimethyl-1, 4,6, 10-tetraene dodecyl diethyl phosphonate with 2, 7-dimethyl-2, 4, 6-octatrienedial in a solvent at 30 ℃ for 3h under the condition of a basic catalyst of potassium tert-butoxide, recrystallizing the reacted product to obtain a lycopene crude product, and heating the lycopene crude product in ethanol and carrying out condensation reflux reaction to obtain the lycopene.

The synthetic route of the method is preferably as follows:

in the present invention, the temperature and pressure are not specified, and both are carried out at room temperature and atmospheric pressure.

The invention designs a total synthetic route by synthesis and inverse synthetic analysis, and based on the organic synthesis theory, by constructing multistep reactions, such as preparation of alpha-substituted-alpha, beta-unsaturated aldehyde, Wittig-Horner reaction and the like, searching for proper synthetic reaction conditions, such as reactant molar ratio, temperature, reaction time, solvent and the like, lycopene is finally synthesized, and the structure of a final product is identified by infrared spectroscopy (IR), High Resolution Mass Spectrometry (HRMS) and Nuclear Magnetic Resonance (NMR), and the result is determined to be a target final product.

Compared with the prior art, the invention has the following advantages and beneficial effects:

1. the invention adopts a brand new technical route and technical means to synthesize the intermediate product 2,6, 10-trimethyl-2, 5, 9-undecane triene-1-aldehyde.

2. The invention adopts a synthesis route characterized by the Wittig-Horner reaction, avoids the problem that byproducts are not easy to separate caused by the Wittig reaction in the prior art, and is a key step for green synthesis of lycopene.

3. The lycopene is synthesized by 3 steps of reaction, compared with the existing lycopene synthesis process, the method has the advantages of short reaction steps, considerable reaction yield and certain industrialization potential.

4. The synthetic method has the advantages that the raw materials are cheap and easy to obtain, the pseudo ionone and the 2, 7-dimethyl-2, 4, 6-octatriene-1, 8-dialdehyde used in the reaction are chemical intermediates commonly applied to the industrial production of the carotenoid, the raw material sources are wide, the production cost is relatively low, and the industrialization is easy to realize.

Detailed Description

The present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto.