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CN113511993B - Synthesis method of beta-apo-8' -ethyl carotenoate - Google Patents

Synthesis method of beta-apo-8' -ethyl carotenoate Download PDF

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CN113511993B
CN113511993B CN202110762043.3A CN202110762043A CN113511993B CN 113511993 B CN113511993 B CN 113511993B CN 202110762043 A CN202110762043 A CN 202110762043A CN 113511993 B CN113511993 B CN 113511993B
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CN113511993A (en
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吴世林
邸维龙
黄海青
张贵东
肖亨
江华峰
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Guangzhou Wisdom Bio Technology Co ltd
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Abstract

The invention relates to the technical field of feed additives, and discloses a synthesis method of beta-apo-8' -ethyl carotenoate, which comprises the following steps: the synthesis of beta-apo-8 '-ethyl caronate by using C10+ C2 → C12, C12+ C15 → C27, C27+ C3 → C30 has the advantages that C10 dialdehyde, vinyl ether (R = alkyl), C15 triphenyl phosphate (X = Br or Cl) and carbethoxyethylidene triphenyl phosphine serving as reactants are rich and cheap in source, vitamin A with high raw material cost is not needed, and the purification steps in the synthesis process are few and simple in operation, so that the synthesis route is low in industrial difficulty and easy to realize large-scale production, and the production cost of beta-apo-8' -ethyl caronate is favorably reduced.

Description

Synthesis method of beta-apo-8' -ethyl carotenoate
Technical Field
The invention relates to the technical field of feed additives, and in particular relates to a synthesis method of beta-apo-8' -ethyl carotenoate.
Background
Beta-apo-8' -ethyl carotenoate, also known as apo ester, belongs to one member of the carotenoid family, is widely used in the feed industry for coloring the skin, the shin and the fat of broilers, particularly broilers, and the yolk of the birds, and is mainly used in the food industry for coloring edible oil, margarine, jam, jelly and drink products thereof. Apoester is a carotenoid synthesized chemically, and the synthetic route mainly comprises the following two types:
1. the British patent publication with publication number GB1137429A and the U.S. patent publication with publication number US5773635A report (C15 + C10+ C5) route:
Figure BDA0003150290830000011
the route can generate 10-15% of beta-carotene in the process of synthesizing C25 aldehyde, the beta-carotene has similar properties with the C25 aldehyde, the beta-carotene can be removed only by repeated crystallization, and the post-treatment is difficult and complicated.
2. The (C20 + C10) route reported in U.S. patent publication No. US 3989785A:
Figure BDA0003150290830000012
Figure BDA0003150290830000021
the raw material C20 triphenyl phosphonium salt used in the route needs to be prepared by vitamin A, so that the cost of the raw material is too high, and the economic value is not large.
Therefore, it is necessary to design a new synthetic route.
Disclosure of Invention
In view of the above, the present invention provides a method for synthesizing beta-apo-8' -ethyl carotenoate, which solves the problems of difficult post-treatment and high raw material cost of the existing apo ester synthesis route, in order to overcome at least one of the disadvantages of the prior art.
In order to solve the technical problems, the invention adopts the following technical scheme:
a synthetic method of beta-apo-8' -ethyl carotenoate comprises the following synthetic routes:
Figure BDA0003150290830000022
wherein the compound 1 is 2, 7-dimethyl-2, 4, 6-octatrienedial (C10 dialdehyde for short); the compound 2 is trimethyl orthoformate; the compound 3 is a vinyl ether (R = alkyl); the compound 4 is a C15 triphenyl phosphonium salt (X = Br or Cl); the compound 5 is carbethoxyethylidene triphenylphosphine; the compound I is 8, 8-dimethoxy-2, 7-dimethyl-2, 4, 6-octatrienal; the compound II is 2, 7-dimethyl-8-methoxyl-2, 4, 6-decatriene-1-aldehyde-10-acetal; the compound III is 12 '-methoxy-beta-apo-10' -carotene acetal; the compound IV is beta-apo-10' -carotenal (C27 aldehyde for short); the compound V is beta-apo-8' -ethyl carotenoate (apo ester for short).
The synthesis method comprises the following steps:
1. synthesis of Compound I
Dissolving C10 dialdehyde in solvent 1, adding trimethyl orthoformate, carrying out catalytic reaction with catalytic amount of acid catalyst, neutralizing with alkali to remove acid catalyst after reaction, adding water for washing, recovering solvent 1 under reduced pressure, adding ethanol for refluxing, cooling, filtering to remove unreacted C10 dialdehyde, and recovering ethanol from mother liquor to obtain compound I.
Wherein the molar ratio of the C10 dialdehyde to trimethyl orthoformate is 1:0.5 to 1, preferably 1:0.5 to 0.7; the solvent 1 is dichloromethane, chloroform, ethyl acetate or toluene, preferably dichloromethane; the acid catalyst is sulfuric acid, p-toluenesulfonic acid, trifluoroacetic acid or nitric acid, preferably trifluoroacetic acid or p-toluenesulfonic acid; the alkali is sodium methoxide or sodium ethoxide.
2. Synthesis of Compound II
Dissolving a compound I in a solvent 2, adding vinyl ether, cooling to-25-5 ℃, adding a catalytic amount of Lewis acid for catalytic reaction, adding water for washing after the reaction is finished, and recovering the solvent 2 under reduced pressure to obtain a compound II.
Wherein the molar ratio of the compound I to the vinyl ether is 1:0.9 to 1.2, preferably 1:1; the vinyl ether is vinyl methyl ether or vinyl ethyl ether, preferably vinyl ethyl ether; the solvent 2 is dichloromethane, toluene, petroleum ether, n-hexane or cyclohexane, and toluene is preferred; the Lewis acid is zinc chloride, ferric chloride or boron trifluoride, and preferably boron trifluoride; the temperature of the reaction is preferably-20 to-15 ℃.
3. Synthesis of Compound III
Dissolving the compound II in a solvent 3, adding C15 triphenyl phosphonium salt, cooling to-15-0 ℃, then dropwise adding alkali liquor, recovering the solvent 3 after the reaction is finished, adding dichloromethane for dissolution, and washing with water to obtain a compound III.
Wherein the molar ratio of the compound II to the C15 triphenyl phosphonium salt is 1:1.0 to 1.5, preferably 1:1.2; the molar ratio of the C15 triphenyl phosphonium salt to the alkali is 1:1 to 1.5, preferably 1:1.1; the alkali liquor is 15-30 wt% of sodium methoxide methanol solution or 10-18 wt% of sodium ethoxide ethanol solution; the solvent 3 is ethanol or methanol; the temperature of the reaction is preferably-5 to-10 ℃.
4. Synthesis of Compound IV
Adding an acid water solution into a dichloromethane solution of the compound III, removing methoxy and aldehyde group protecting groups, separating a water layer after the reaction is finished, recovering dichloromethane, adding ethanol for refluxing, cooling, filtering and drying to obtain a mauve compound IV.
Wherein the aqueous solution of the acid is 0.5 to 15 weight percent of aqueous solution of sulfuric acid, trifluoroacetic acid, nitric acid or hydrochloric acid; the volume ratio of the dichloromethane to the acid aqueous solution is 1:1 to 3.
5. Synthesis of Compound V
Adding the compound IV and carbethoxyethylidene triphenylphosphine into a solvent 4, refluxing, cooling to 35-45 ℃ after the reflux is finished, filtering and drying to obtain beta-apo-8' -ethyl carotenoate.
Wherein the molar ratio of the compound IV to the carbethoxyethylidene triphenylphosphine is 1:1 to 1.25; the solvent 4 is ethanol, toluene or cyclohexane, preferably ethanol.
The invention designs a route for synthesizing beta-apo-8 '-ethyl caronate by C10+ C2 → C12, C12+ C15 → C27, C27+ C3 → C30, wherein C10 dialdehyde, vinyl ether (R = alkyl), C15 triphenyl phosphate (X = Br or Cl) and carbethoxyethylidene triphenyl phosphine which are used as reactants have rich and cheap sources, vitamin A with high raw material cost is not needed, and the synthesis process has few purification steps and simple operation, so that the synthesis route has low industrial difficulty and is easy to realize large-scale production, and the production cost of the beta-apo-8' -ethyl caronate is favorably reduced.
Compared with the prior art, the invention has the following beneficial effects: 1. the purification steps are few, and the operation is simple; 2. the raw material source is rich and cheap; 3. the industrialization difficulty is not large, and the large-scale production is easy to realize.
Detailed Description
The invention designs a route for synthesizing beta-apo-8' -ethyl carotenoate by C10+ C2 → C12, C12+ C15 → C27, C27+ C3 → C30, which comprises the following steps:
Figure BDA0003150290830000041
Figure BDA0003150290830000051
in order to make the technical solutions of the present invention better understood by those skilled in the art, the present invention is further described in detail with reference to the following specific embodiments.
Example 1
The method for synthesizing beta-apo-8' -ethyl carotenoate according to the route comprises the following steps:
s1, synthesizing a compound I
Figure BDA0003150290830000052
Dissolving 16.4g (0.1 mol) of C10 dialdehyde in 120ml of dichloromethane, adding 7.42g (0.07 mol) of trimethyl orthoformate and 0.3 g of p-toluenesulfonic acid for catalytic reaction, maintaining the reaction temperature at 30-35 ℃ for reaction, tracking the reaction by using a liquid phase, taking the end point when the increment of the product content is 0.3-0.5% in half an hour, adding 0.1g of sodium methoxide for neutralization reaction, washing with 40ml of multiplied by 2 water, decompressing and recovering dichloromethane, adding 200ml of absolute ethyl alcohol for refluxing for half an hour after recovery is finished, recovering dichloromethane and recovering the residual methanol after the reaction is finished, wherein the residual methanol is removedCooling to room temperature, filtering to obtain 4.1g of unreacted C10 dialdehyde, recovering ethanol from the mother liquor to obtain compound I, and calculating the yield according to the actually consumed C10 dialdehyde (actually fed-recovered raw material) to obtain 14.3 g of target product with the content of 96.6% and the yield of 90.8%. 1 H-NMR(300MHz,CDCl 3 ):10.12(1H,-CHO),6.10～7.62(4H,-CH＝),4.35(1H,CH),3.21(6H,-OCH 3 ) 1.96 (alkenylmethyl hydrogen).
S2. Synthesis of Compound II
Figure BDA0003150290830000053
21.74g (content 96.6%,0.1 mol) of the compound I obtained in the step S1 is dissolved in 150ml of toluene, then 7.2g (0.1 mol) of vinyl ethyl ether is added, the mixture is cooled to-20 to-15 ℃, then 0.2g of boron trifluoride is added for catalytic reaction, TLC is used for tracking reaction, water washing is added after the reaction is finished, the solvent is recovered under reduced pressure, 29.2g of crude compound II is obtained, the content of liquid phase analysis is 89.7%, and the yield is 92.9%. 1 H-NMR(300MHz,CDCl 3 ) 10.10 (1H, -CHO), 6.25 to 7.52 (4H, -CH =), 4.32 (1H, acetal hydrocarbon), 1.12 (3H, -O-CH) 2 CH* 3 ) (ii) a 3.51 (1H, tertiary hydrocarbon); 3.40 (2H, -O-CH- 2 CH 3 ),3.21(6H,-OCH 3 ),1.95(2H,-CH 2 -, 1.82 (alkenylmethylhydrogen).
S3, synthesizing a compound III
Figure BDA0003150290830000061
31.4g (content: 89.7%,0.1 mol) of the compound II obtained in the step S2 was dissolved in 280ml of methanol, 65.46g (0.12 mol) of brominated C15 triphenyl phosphonium salt was cooled to-5 to-10 ℃, 27.36 g of a 30wt% sodium methoxide methanol solution was added dropwise over 1 hour, the incubation reaction was continued, the TLC-follow-up reaction was carried out, methanol was recovered after the reaction was completed, 200ml of dichloromethane was added to dissolve the compound II, and 50ml of X3 water was added to wash the compound II to obtain a compound III, which was directly used in the next step without purification. 1 H-NMR(300MHz,CDCl 3 ):1.00(6H,C(CH 3 ) 2 ) 1.68 (3H, cyclomethylhydrogen), 1.46 (2H, -CH) 2 -),1.60(2H,-CH 2 -),1.98(2H,-CH 2 -),1.83(9H,-CH 3 ) 6.25 to 6.82 (9H, -CH =), 4.32 (1H, acetal hydrocarbon), 1.10 (3H, -O-CH) 2 CH* 3 ) (ii) a 3.51 (1H, tertiary hydrocarbon); 3.40 (2H, -O-CH;) 2 CH 3 ),3.21(6H,-OCH 3 ),1.95(2H,-CH 2 -)。
S4, synthesizing a compound IV
Figure BDA0003150290830000062
And (2) adding 250ml of trifluoroacetic acid aqueous solution with the concentration of 5wt% into the dichloromethane solution of the compound III obtained in the step (S3), fully stirring and reacting for 3 hours under reflux, separating a water layer after the reaction is finished, recovering dichloromethane, adding 250ml of ethanol for refluxing, cooling, filtering and drying to obtain 30.1g of a mauve compound IV (C27 aldehyde), wherein the content of a liquid phase is 97.3 percent, and the yield is 80 percent based on the compound II. 1 H-NMR(300MHz,CDCl 3 ):1.01(6H,C(CH 3 ) 2 ) 1.68 (3H, cyclomethylhydrogen), 1.46 (2H, -CH) 2 -),1.60(2H,-CH 2 -),1.98(2H,-CH 2 -),1.83(9H,-CH 3 ),6.25～6.88(11H,-CH＝),9.85(1H,-CHO)。
S5, synthesizing a compound V
Figure BDA0003150290830000071
37.7g (0.1 mol) of C27 aldehyde and 43.4g (0.12 mol) of carbethoxyethylidene triphenylphosphine are added into 250ml of ethanol to be heated and refluxed for 2 hours, the mixture is cooled to 35 to 45 ℃ after the reflux is finished, and 38.2g of beta-apo-8' -ethyl caronate is obtained after filtration and drying, the content is 96.1 percent, and the yield is 83 percent. 1 H-NMR(300MHz,CDCl 3 ):1.01(6H,C(CH 3 ) 2 ) 1.68 (3H, cyclomethylhydrogen), 1.46 (2H, -CH 2-), 1.60 (2H, -CH) 2 -),1.98(2H,-CH 2 -),1.83(12H,-CH 3 ),6.25～6.88(12H,-CH＝),1.10(3H,-O-CH 2 CH* 3 )；3.40(2H,-O-CH* 2 CH 3 )。
Example 2
S1, synthesizing a compound I
Figure BDA0003150290830000072
Dissolving 16.4g (0.1 mol) of C10 dialdehyde in 120ml of dichloromethane, adding 5.3g (0.05 mol) of trimethyl orthoformate and 0.3 g of p-toluenesulfonic acid for catalytic reaction, maintaining the reaction temperature at 30-35 ℃ for reaction, tracking the reaction by using a liquid phase, taking the end point when the increment of the product content is 0.3-0.5% in half an hour, adding 0.1g of sodium methoxide for neutralization reaction, washing with 40ml of multiplied by 2 water, then decompressing and recovering dichloromethane, after recovery, adding 200ml of absolute ethyl alcohol for refluxing for half an hour, cooling to room temperature, filtering to obtain 8.6g of unreacted C10 dialdehyde, recovering ethanol from mother liquor to obtain a compound I, and obtaining 9.3 g of target product according to the yield of actually consumed C10 dialdehyde (actual feeding-recovered raw material), wherein the content is 96.2%, and the yield is 93.1%.
S2. Synthesis of Compound II
Figure BDA0003150290830000081
21.74g (content: 96.6%,0.1 mol) of the compound I obtained in the step S1 is dissolved in 150ml of toluene, then 6.48g (0.09 mol) of vinyl ethyl ether is added, the mixture is cooled to-20 to-15 ℃, then 0.2g of boron trifluoride is added for catalytic reaction, TLC tracking reaction is carried out, after the reaction is finished, water is added for washing, the solvent is recovered under reduced pressure, 28.8g of crude compound II is obtained, the content of liquid phase analysis is 87.7%, and the yield is 91.8%.
S3, synthesizing a compound III
Figure BDA0003150290830000082
31.4g (content: 89.7%,0.1 mol) of the compound II obtained in the step S2 is dissolved in 280ml of methanol, 54.55g (0.1 mol) of brominated C15 triphenyl phosphonium salt is cooled to-5-10 ℃, 44.57 g of methanol solution of 20wt% sodium methoxide is dripped in for 1 hour, then the heat preservation reaction is continued, the TLC tracking reaction is carried out, the methanol is recovered after the reaction is finished, 200ml of dichloromethane is added for dissolution, and 50ml of multiplied by 3 water is washed to obtain a compound III, and the compound III directly enters the next step without being purified.
S4, synthesizing a compound IV
Figure BDA0003150290830000083
Adding 200ml of trifluoroacetic acid aqueous solution with the concentration of 0.5wt% into the dichloromethane solution of the compound III obtained in the step S3, fully stirring and reacting for 3 hours under reflux, separating a water layer after the reaction is finished, recovering dichloromethane, adding 250ml of ethanol for refluxing, cooling, filtering and drying to obtain 28.6g of a mauve compound IV (C27 aldehyde), wherein the content of a liquid phase is 97.1 percent, and the yield is 76 percent by taking the compound II as a reference.
S5, synthesizing a compound V
Figure BDA0003150290830000091
37.7g (0.1 mol) of C27 aldehyde and 36.17g (0.1 mol) of carbethoxyethylidene triphenylphosphine are added into 250ml of ethanol, heated and refluxed for 2 hours, cooled to 35-45 ℃ after the reflux is finished, filtered and dried to obtain 36.4g of beta-apo-8' -ethyl caronate with the content of 96.1 percent and the yield of 79 percent.
Example 3
S1, synthesizing a compound I
Figure BDA0003150290830000092
Dissolving 16.4g (0.1 mol) of C10 dialdehyde in 120ml of dichloromethane, adding 10.6g (0.1 mol) of trimethyl orthoformate, carrying out catalytic reaction by 0.3 g of p-toluenesulfonic acid, maintaining the reaction temperature at 30-35 ℃ for reaction, tracking the reaction by using a liquid phase, taking the end point when the increment of the product content is 0.3-0.5% in half an hour, adding 0.1g of sodium methoxide for neutralization reaction, washing by 40ml of multiplied by 2 water, then decompressing and recovering dichloromethane, after recovery, adding 200ml of absolute ethyl alcohol for refluxing for half an hour, cooling to room temperature, filtering to obtain 10g of unreacted C10 dialdehyde, recovering ethanol from mother liquor to obtain a compound I, and calculating the yield according to the actually consumed C10 dialdehyde (actually fed material-recovered raw material) to obtain 7.1 g of target product, the content is 96.5%, and the yield is 86.8%.
S2. Synthesis of Compound II
Figure BDA0003150290830000101
Dissolving 21.74g (content: 96.6%,0.1 mol) of the compound I obtained in the step S1 in 150ml of toluene, adding 8.64g (0.12 mol) of vinyl ethyl ether, cooling to-20-15 ℃, adding 0.2g of boron trifluoride to perform catalytic reaction, tracking the reaction by TLC, washing with water after the reaction is finished, and recovering the solvent under reduced pressure to obtain 30.2g of a crude compound II, wherein the content of the compound I by liquid phase analysis is 79.4%, and the yield is 85%.
S3, synthesizing a compound III
Figure BDA0003150290830000102
31.4g (content: 89.7%,0.1 mol) of the compound II obtained in the step S2 is dissolved in 280ml of methanol, 81.825g (0.15 mol) of brominated C15 triphenyl phosphonium salt is cooled to-5-10 ℃, 81.036 g of methanol solution of sodium methoxide with the concentration of 15wt% is dripped into the solution for 1 hour, the heat preservation reaction and the TLC tracking reaction are continued, the methanol is recovered after the reaction is finished, 200ml of dichloromethane is added for dissolution, and 50ml of multiplied by 3 water is added for washing to obtain a compound III, and the compound III directly enters the next step without purification.
S4, synthesizing a compound IV
Figure BDA0003150290830000103
600ml of a trifluoroacetic acid aqueous solution with a concentration of 15wt% was added to the dichloromethane solution of the compound III obtained in the step S3, and the mixture was sufficiently stirred under reflux for reaction for 3 hours, after the reaction was completed, the aqueous layer was separated, dichloromethane was recovered, 250ml of ethanol was further added for reflux, and 28.6g of a magenta compound IV (C27 aldehyde) was obtained by cooling, filtering, and drying, the liquid phase content was 97%, and the yield was 76% based on the compound II.
S5, synthesizing a compound V
Figure BDA0003150290830000111
37.7g (0.1 mol) of C27 aldehyde and 45.2g (0.125 mol) of carbethoxyethylidene triphenylphosphine are added into 250ml of ethanol and heated and refluxed for 2 hours, the mixture is cooled to 35 to 45 ℃ after the reflux is finished, and the mixture is filtered and dried to obtain 37.28g of beta-apo-8' -ethyl carotenoate with the content of 96.2 percent and the yield of 83 percent.
Example 4
This example examines the effect of different solvents 1 on the yield of the synthesis compound I. The procedure is as in example 1 except that chloroform, ethyl acetate and toluene are used instead of dichloromethane. The results are given in the following table:
solvent 1 Methylene dichloride Chloroform Ethyl acetate Toluene
Quality of target product 14.3 g 13.6 g 10g 12 g
Content of the target product 96.6％ 95％ 82％ 96％
Yield of the target product 90.8％ 86.4 78％ 76.2％
Example 5
This example examines the effect of different acid catalysts on the yield of synthesis compound I. The same procedure as in example 1 was repeated except that sulfuric acid, trifluoroacetic acid and nitric acid were used instead of p-toluenesulfonic acid. The results are given in the following table:
acid catalyst Para toluene sulfonic acid Sulfuric acid Trifluoroacetic acid Nitric acid
Quality of the target product 14.3 g 14.7 g 12 g 7g
Content of the target product 96.6％ 97.3％ 95.5％ 97％
Yield of the target product 90.8％ 93.3％ 76.2％ 44.4％
Example 6
This example examines the effect of different bases on the yield of the synthesis compound I. The procedure is as in example 1 except that sodium ethoxide is used instead of sodium methoxide. 14.5 g of the expected product are finally obtained, the content is 97%, and the yield is 92.1%.
Example 7
This example investigates the effect of different vinyl ethers on the yield of synthesis compound II. The same procedure as in example 1 was repeated except that vinyl methyl ether was used instead of vinyl ethyl ether. 27.5g of crude compound II was finally obtained, the content by liquid phase analysis was 90.7%, and the yield was 93.1%.
Example 8
This example examines the effect of different solvents 2 on the yield of synthetic compound II. The procedure of example 1 was repeated except that methylene chloride, petroleum ether, n-hexane and cyclohexane were used instead of toluene. The results are given in the following table:
solvent 2 Toluene Methylene dichloride Petroleum ether N-hexane Cyclohexane
Quality of target product 29.2g 29 g 28.4 g 27 g 27.2 g
Content of target product 89.7％ 85％ 88％ 89.1％ 86.6％
Yield of the target product 92.9％ 87.4 88.6％ 85.3％ 83.5％
Example 9
This example investigates the effect of different lewis acids on the yield of synthesis compound II. The procedure of example 1 was repeated except that zinc chloride and ferric chloride were used instead of boron trifluoride. The results are given in the following table:
lewis acid Boron trifluoride Zinc chloride Ferric chloride
Quality of the target product 29.2g 29.1 g 28.8g
Content of target product 89.7％ 81.1％ 85.2％
Yield of the target product 92.9％ 83.7％ 87.1％
Example 10
This example examines the effect of different alkalis on the yield of the synthesis compound III. The same procedure as in example 1 was repeated except that a methanol solution of sodium methoxide of 15wt%, an ethanol solution of sodium ethoxide of 10wt%, and an ethanol solution of sodium ethoxide of 18wt% were used instead of the methanol solution of sodium methoxide of 30wt%, respectively. The results are given in the following table:
Figure BDA0003150290830000121
example 11
This example examines the effect of different solvents 3 on the yield of the synthesis compound III. The procedure is as in example 1 except that ethanol is used instead of methanol. The final compound 23 g, content 96.6%, yield 61.1%.
Example 12
This example examines the effect of aqueous solutions of different acids on the yield of the synthesis compound IV. The same procedure as in example 1 was repeated except that aqueous solutions of sulfuric acid, nitric acid and hydrochloric acid were used instead of the aqueous solution of trifluoroacetic acid. The results are given in the following table:
Figure BDA0003150290830000122
Figure BDA0003150290830000131
example 13
This example examines the effect of different solvents 4 on the yield of synthetic compound V. The same procedure as in example 1 was repeated except that toluene and cyclohexane were used instead of ethanol. The results are given in the following table:
solvent 4 Ethanol Toluene Cyclohexane
Quality of the target product 38.2g 32.6 g 33.4 g
Content of target product 96.1％ 95.8％ 95.3％
Yield of the target product 83％ 70.8％ 72.6％
It should be understood that the above-described embodiments of the present invention are merely examples for clearly illustrating the present invention and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.

Claims (8)

1. A synthetic method of beta-apo-8' -ethyl carotenoate is characterized in that the synthetic route is as follows:
Figure FDA0004038873450000011
wherein the compound 1 is 2, 7-dimethyl-2, 4, 6-octatrienedial; the compound 2 is trimethyl orthoformate; compound 3 is a vinyl ether, wherein R = alkyl; the compound 4 is a C15 triphenyl phosphonium salt, wherein X = Br or Cl; the compound 5 is carbethoxyethylidene triphenylphosphine; the compound I is 8, 8-dimethoxy-2, 7-dimethyl-2, 4, 6-octatrienal; the compound II is 2, 7-dimethyl-8-methoxyl-2, 4, 6-decatriene-1-aldehyde-10-acetal; the compound III is 12 '-methoxy-beta-apo-10' -carotene acetal; the compound IV is beta-apo-10' -carotenal; the compound V is beta-apo-8' -ethyl carotenoate.
2. The process for the synthesis of ethyl beta-apo-8' -carotenoate according to claim 1, characterized by the synthesis of compound I: dissolving C10 dialdehyde in solvent 1, adding trimethyl orthoformate, carrying out catalytic reaction with catalytic amount of acid catalyst, neutralizing the acid catalyst with alkali after the reaction is finished, adding water for washing, then recovering solvent 1 under reduced pressure, adding ethanol for refluxing, cooling, filtering to remove unreacted C10 dialdehyde, and recovering ethanol from mother liquor to obtain compound I.
3. The process for the synthesis of ethyl beta-apo-8' -carotenoate according to claim 2, characterized by the synthesis of compound II: dissolving a compound I in a solvent 2, adding vinyl ether, cooling to-25-5 ℃, adding a catalytic amount of Lewis acid for catalytic reaction, adding water for washing after the reaction is finished, and recovering the solvent 2 under reduced pressure to obtain a compound II.
4. The process for the synthesis of ethyl beta-apo-8' -carotenoate according to claim 3, characterized by the synthesis of compound III: dissolving the compound II in a solvent 3, adding C15 triphenyl phosphonium salt, cooling to-15-0 ℃, then dropwise adding alkali liquor, recovering the solvent 3 after the reaction is finished, adding dichloromethane for dissolution, and washing with water to obtain a compound III.
5. The process for the synthesis of ethyl beta-apo-8' -carotenoate according to claim 4, characterized by the fact that the synthesis of compound IV: adding an acid water solution into a dichloromethane solution of the compound III, removing methoxy and aldehyde group protecting groups, separating a water layer after the reaction is finished, recovering dichloromethane, adding ethanol for refluxing, cooling, filtering and drying to obtain a mauve compound IV.
6. The process for the synthesis of ethyl beta-apo-8' -carotenoate according to claim 5, characterized by the synthesis of compound V: adding the compound IV and carbethoxyethylidene triphenylphosphine into a solvent 4, refluxing, cooling to 35-45 ℃ after the reflux is finished, filtering and drying to obtain beta-apo-8' -ethyl carotenoate.
7. The process for synthesizing ethyl beta-apo-8' -carotenoate according to claim 6,
in the synthesis of the compound I: the molar ratio of the C10 dialdehyde to trimethyl orthoformate is 1:0.5 to 1; and/or the solvent 1 is dichloromethane, chloroform, ethyl acetate or toluene; and/or the acid catalyst is sulfuric acid, p-toluenesulfonic acid, trifluoroacetic acid or nitric acid; and/or the base is sodium methoxide or sodium ethoxide; and/or
In the synthesis of said compound II: the molar ratio of the compound I to the vinyl ether is 1:0.9 to 1.2; and/or the vinyl ether is vinyl methyl ether or vinyl ethyl ether; and/or the solvent 2 is dichloromethane, toluene, petroleum ether, n-hexane or cyclohexane; and/or the lewis acid is zinc chloride, ferric chloride or boron trifluoride; and/or the temperature of the reaction is-20 to-15 ℃; and/or
In the synthesis of said compound III: the molar ratio of the compound II to the C15 triphenyl phosphonium salt is 1:1.0 to 1.5; and/or the molar ratio of the C15 triphenyl phosphonium salt to the base is 1:1 to 1.5; and/or the solvent 3 is ethanol or methanol; and/or the alkali liquor is 15-30 wt% of methanol solution of sodium methoxide or 10-18 wt% of ethanol solution of sodium ethoxide; the temperature of the reaction is-5 to-10 ℃; and/or
In the synthesis of the compound IV: the aqueous solution of the acid is 0.5 to 15 weight percent of aqueous solution of sulfuric acid, trifluoroacetic acid, nitric acid or hydrochloric acid; the volume ratio of the dichloromethane to the acid aqueous solution is 1:1 to 3; and/or
In the synthesis of compound V: the molar ratio of the compound IV to the carbethoxyethylidene triphenylphosphine is 1:1 to 1.25; and/or the solvent 4 is ethanol, toluene or cyclohexane.
8. The process for synthesizing beta-apo-8' -carotenoic acid ethyl ester according to claim 7,
in the synthesis of the compound I: the molar ratio of the C10 dialdehyde to trimethyl orthoformate is 1:0.5 to 0.7; and/or the solvent 1 is dichloromethane; and/or the acid catalyst is trifluoroacetic acid or p-toluenesulfonic acid; and/or
In the synthesis of said compound II: the molar ratio of the compound I to the vinyl ether is 1:1; and/or the vinyl ether is vinyl ethyl ether; and/or the solvent 2 is toluene; and/or the lewis acid is boron trifluoride; and/or
In the synthesis of said compound III: the molar ratio of the compound II to the C15 triphenyl phosphonium salt is 1:1.2; and/or the molar ratio of the C15 triphenyl phosphonium salt to the base is 1:1.1; and/or
In the synthesis of compound V: the solvent 4 is ethanol.
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CN1215723A (en) * 1997-10-03 1999-05-05 霍夫曼-拉罗奇有限公司 Preparation method of carotenoid
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Denomination of invention: A synthetic method for b - Apo-8 '- carotene ethyl ester

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