Beta-carotene synthesis (II)
By using a method of reacting specific alcohol solvents with halogen compounds, the problem of solvent selection affecting yield and purity in the existing β-carotene production is solved, and efficient and environmentally friendly β-carotene production is achieved.
Patent Information
- Application Number
- CN202380068841.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2022-09-29
- Filing Date
- 2023-09-25
- Publication Date
- 2025-05-06
AI Technical Summary
In the existing β-carotene production methods, the selection of solvents has an impact on yield and purity, and the commonly used ethanol solvents are inconvenient to regenerate.
Specific alcohol solvents, such as 1-pentanol, 2-pentanol, 2-methyl-butane-1-ol, 2-methyl-2-butanol and 3-methyl-1-butanol are used as solvents to produce β-carotene by reacting with a halogen compound.
The high yield and high purity production of β-carotene is achieved, while the halogen-free and non-aromatic solvents used are environmentally friendly and easy to regenerate.
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Abstract
Description
[0001] The present invention relates to a method for producing beta-carotene in a specific solvent.
[0002] Beta-carotene is an organic, intense red-orange pigment found in abundance in fungi, plants and fruits. Beta-carotene is an important product that has many different applications.
[0003] β-carotene is a compound of formula (I)
[0004]
[0005] β-Carotene is a member of the carotenes, which are terpenoids (isoprenoids) biochemically synthesized from eight isoprene units and thus have 40 carbons. Among the carotenes, β-carotene is distinguished by having β-rings at both ends of the molecule.
[0006] Beta-carotene is the most common form of carotene found in plants.
[0007] When used as a food coloring, its E number is E160a(ii).
[0008] Furthermore, in nature, β-carotene is a precursor (inactive form) of vitamin A formed through the action of β-carotene 15,15'-monooxygenase.
[0009] Beta-carotene is the compound that gives vegetables their vibrant yellow, orange, and red colors. The body converts beta-carotene into vitamin A (retinol).
[0010] In addition to its coloring properties, beta-carotene has several health benefits, such as effects on eye health, improved cognitive function, skin protection, and cancer prevention.
[0011] The common method of producing beta-carotene is shown in the scheme below:
[0012]
[0013] Because of its importance, there is always a need for improved methods of obtaining beta-carotene.
[0014] Surprisingly, we have found that the choice of a specific solvent leads to excellent yields and excellent purity of the resulting β-carotene.
[0015] The specific solvent is an alcohol represented by a compound of formula (IV),
[0016] R-OH(IV),
[0017] Where R is a straight or branched C3-C 10-alkyl fragment.
[0018] Therefore, the present invention relates to a process (P) for producing a compound of formula (I),
[0019]
[0020] wherein a compound of formula (II) is reacted with a compound of formula (III),
[0021]
[0022] wherein X is a halogen (preferably Cl, Br or I),
[0023] characterised in that at least one compound of formula (IV) is used as solvent,
[0024] R-OH(IV),
[0025] Where R is a straight or branched C3-C 10 Alkyl fragment.
[0026] In the context of the present invention, all disclosed compounds (represented by chemical formulae) may be in any possible stereochemical configuration.
[0027] The method according to the invention has several advantages.
[0028] A major advantage of the improved synthesis of the present invention is that the solvent (or mixture of solvents) used is halogen-free and non-aromatic. This means that the solvent used is environmentally friendly. In addition, the solvent used in the novel method according to the present invention can be easily regenerated. When ethanol is used (as in many prior art methods), this regeneration is not so easy to carry out.
[0029] Preferably, compounds of formula (II) are used, wherein X is Cl, Br or I.
[0030] More preferably, a compound of formula (IIa) is used,
[0031]
[0032] Therefore, the present invention relates to process (P1) which is process (P), wherein a compound of formula (II) wherein X is Cl, Br or I is used.
[0033] Therefore, the present invention relates to process (P1') which is process (P) wherein a compound of formula (IIa) is used,
[0034]
[0035] The process according to the invention is carried out in at least one alcohol of the formula (IV) as solvent.
[0036] Preferably, the process according to the invention is carried out in at least one compound of the formula (IV) in which R is a linear or branched C4-C8-alkyl fragment.
[0037] More preferably, the process according to the invention is carried out in at least one compound of the formula (IV) in which R is a linear or branched C4-C7-alkyl fragment.
[0038] Particularly preferred are compounds of formula (IV) wherein R is a linear or branched C5 alkyl moiety.
[0039] Most preferably, 1-pentanol, 2-pentanol, 2-methyl-butan-1-ol, 2-methyl-2-butanol and / or 3-methyl-1-butanol are used as solvent.
[0040] Even more preferred is a mixture of 2-methyl-2-butanol and 3-methyl-1-butanol.
[0041] Most preferred is 25:75 (weight % with respect to solvent, based on the total weight of the solvent mixture) of 2-methyl-2-butanol and 3-methyl-1-butanol.
[0042] The invention therefore relates to process (P2) which is process (P), (P1) or (P1′), wherein the process is carried out in at least one alcohol of the formula (IV) in which R is a linear or branched C4-C8-alkyl fragment.
[0043] The invention therefore relates to process (P2') which is process (P), (P1) or (P1'), wherein the process is carried out in at least one alcohol of the formula (IV) in which R is a linear or branched C4-C7-alkyl fragment.
[0044] The present invention therefore relates to process (P2") which is process (P), (P1) or (P1'), wherein the process is carried out in at least one alcohol of the formula (IV) in which R is a linear or branched C5-alkyl fragment.
[0045] Therefore, the present invention relates to process (P2'') which is process (P), (P1) or (P1'), wherein the process is carried out in 1-pentanol, 2-pentanol, 2-methyl-butan-1-ol, 2-methyl-2-butanol and / or 3-methyl-1-butanol.
[0046] Therefore, the present invention relates to process (P2"") which is process (P), (P1) or (P1'), wherein the process is carried out in a mixture of 2-methyl-2-butanol and 3-methyl-1-butanol.
[0047] Therefore, the present invention relates to process (P2""') which is process (P), (P1) or (P1'), wherein the process is carried out in a mixture of 2-methyl-2-butanol and 3-methyl-1-butanol in a ratio of 25:75 (wt. % relating to the solvent, based on the total weight of the solvent mixture).
[0048] Typically, a base is also added to the reaction mixture.
[0049] The base is typically an alkali metal hydroxide, an alkaline earth metal hydroxide, an alkali metal carbonate, an alkaline earth metal carbonate, KF / Al2O3, NaOCH3 and KOCH3.
[0050] Preferably, the base is CsOH, KOH, NaOH, Na2CO3, K2CO3 or Na2CO3.
[0051] The base is usually used in a molar excess relative to the compound of formula (III), usually 2 to 20 molar equivalents relative to the compound of formula (III).
[0052] Therefore, the present invention relates to process (P3) which is process (P), (P1), (P1'), (P2), (P2'), (P2"), (P2"'), (P2"") or (P2""'), wherein the process is carried out in the presence of at least one base.
[0053] The present invention therefore relates to a process (P3') which is process (P3), wherein the base is selected from the group consisting of alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates, alkaline earth metal carbonates, KF / Al2O3, NaOCH3 and KOCH3.
[0054] Therefore, the present invention relates to a process (P3") which is process (P3), wherein the base is selected from the group consisting of CsOH, KOH, NaOH, Na2CO3 and K2CO3.
[0055] The amount of the compound of formula (II) used is at least 2 molar equivalents (with respect to the compound of formula (III)).
[0056] Therefore, the present invention relates to method (P4), which is method (P), (P1), (P1'), (P2), (P2'), (P2"), (P2"'), (P2""), (P2""'), (P3), (P3') or (P3"), wherein the amount of compound of formula (II) used is at least 2 molar equivalents (with respect to the compound of formula (III)).
[0057] The compound of formula (IV) is used as a solvent and is therefore used in excess relative to the compound of formula (II) and the compound of formula (III).
[0058] Normally and preferably the base is used in the process according to the invention in an excess of the compound of formula (II).
[0059] Typically and preferably, the amount used is from 1.5 to 4 molar equivalents (with respect to the compound of formula (II)).
[0060] Therefore, the present invention relates to process (P5) which is process (P3), (P3′) or (P3″), wherein the at least one base is used in an amount of 1.5 to 4 molar equivalents (with respect to the compound of formula (II)).
[0061] The process according to the invention is generally carried out at a temperature of -5°C to 120°C.
[0062] Therefore, the present invention relates to process (P6), which is process (P), (P1), (P1'), (P2), (P2'), (P2"), (P2"'), (P2""), (P2""'), (P3), (P3'), (P3"), (P4) or (P5), wherein the process according to the invention is typically carried out at a temperature of -5°C to 120°C.
[0063] The following examples further illustrate the present invention without limiting it. All percentages and parts given are by weight and temperatures are given in ° C. and pressures are absolute unless otherwise stated. Example
[0064] Example 1
[0065] Under an inert gas atmosphere, C as a compound of formula (III) 10 -dialdehyde (0.53g, 1 equivalent, 3.2mmol) and vinyl salt (5.0g, 2.3 equivalents, 7.4mmol) as a compound of formula (IIa) were suspended in 1-pentanol (14.9mL). The yellow suspension was warmed to 38°C. Sodium hydroxide solution (2.8g, 2.6mL, 10% by weight, 2.2 equivalents, 7.1mmol) was added dropwise over 16 hours. The reaction mixture was then stirred at 40°C for another hour and at 100°C for 1 hour. After 30 minutes at 100°C, the color change from orange to purple indicated a change in the crystal form. The oil bath was removed and the reaction mixture was cooled to 40°C. Then, 5mL of deionized water was added and the reaction mixture was cooled to 20°C. The red suspension was filtered and the filter cake was subsequently rinsed with amyl alcohol and water. The red crystals were dried overnight under vacuum at 50°C.
[0066] The product was obtained as dark purple crystals in 86% yield and 93.7% purity (1.58 g).
[0067] Example 2
[0068] Under an inert atmosphere, a solution of the vinyl salt in amyl alcohol (13.1 g, 25.9 wt%, 2.1 eq, 6.75 mmol) was adjusted to neutral pH with aqueous sodium hydroxide solution (5%). 10 -dialdehyde (0.530g, 1 equivalent, 3.21mmol) and amyl alcohol (5mL). The yellow suspension is cooled to 0°C. Sodium hydroxide solution (2.3g, 2.1mL, 10% by weight, 1.76 equivalents, 5.66mmol) is added within 2 hours. Afterwards, a second portion of sodium hydroxide solution (0.57g, 0.51mL, 10% by weight, 0.44 equivalents, 1.41mmol) is also added within 2 hours. Then, the reaction mixture is warmed to 40°C and stirred for 1 hour, and then heated to reflux for another 1 hour. After 30 minutes, the color change from orange to purple indicates the change of crystal form. Remove the oil bath and cool the reaction mixture to 40°C. Deionized water (5mL) is added and the reaction mixture is cooled to 0°C. The red suspension is filtered, and the filter cake is then rinsed with amyl alcohol and water. The red crystals are dried overnight at 50°C under vacuum.
[0069] The product was obtained as dark purple crystals in 90% yield and 92.8% purity (1.67 g).
[0070] Example 3
[0071] In a 1-liter reactor, C 10 -dialdehyde (9.03 g) (which is a compound of formula (III)) and anhydrous K2CO3 (18.9 g), and 3-methyl-1-butanol (97.5 g) are added. The mixture is heated to an internal temperature of 40° C. Thereafter, the vinyl salt of the compound of formula (IIa) (60.1 g) dissolved in 156 g of 3-methyl-1-butanol is added (the maximum concentration of water in the mixture must not exceed 2% by weight). The addition is completed over a period of 60 minutes.
[0072] After the addition of the vinyl salt solution was complete, the dark red suspension was stirred for 240 minutes at 40° C. At the end of this time, a further 0.02 equivalents of the vinyl salt (as a solution in 3-methyl-1-butanol) were added.
[0073] The reaction mixture was heated to 90° C. The reaction mixture was maintained at this temperature for a further 2 hours.
[0074] Finally the reaction mixture was cooled to 20°C and deionized water (150 g) was added. The solid was filtered off.
[0075] The solid product was washed with MeOH (90.0 g), water (200 g), and finally washed again with MeOH (90.0 g).The dark purple solid was dried under reduced pressure at 40°C for 8 hours.
[0076] Yield: 28.41 g of crude β-carotene, a mixture of isomers of all-trans β-carotene (85-92 wt %) and β-carotene cis isomers (8-15 wt %).
Claims
1. A method for producing a compound of formula (I), wherein a compound of formula (II) is reacted with a compound of formula (III), Where X is a halogen, Features At least one compound of formula (IV) is used as solvent, R-OH(IV), Where R is a straight or branched C3-C 10 Alkyl fragment.
2. The process according to claim 1, wherein a compound of formula (II) is used, wherein X is Cl, Br or I.
3. The method according to claim 1, wherein a compound of formula (IIa) is used, 4. The process according to any one of the preceding claims, wherein the process is carried out in at least one alcohol of formula (IV) wherein R is a linear or branched C4-C8 alkyl fragment.
5. The process according to any one of the preceding claims 1 to 3, wherein the process is carried out in at least one alcohol of formula (IV), wherein R is a linear or branched C5 alkyl fragment.
6. The process according to any one of the preceding claims 1 to 3, wherein the process is carried out in 1-pentanol, 2-pentanol, 2-methyl-butan-1-ol, 2-methyl-2-butanol and / or 3-methyl-1-butanol.
7. The process according to any one of the preceding claims, wherein the process is carried out in the presence of at least one base.
8. The process according to claim 7, wherein the base is an alkali metal hydroxide, an alkaline earth metal hydroxide, an alkali metal carbonate, an alkaline earth metal carbonate, KF / Al2O3, NaOCH3 and KOCH3.
9. The method of claim 7, wherein the base is selected from the group consisting of CsOH, KOH, NaOH, Na2CO3 and KCO3.
10. The process according to any one of the preceding claims 7 to 9, wherein the at least one base is used in an amount of 1.5 to 4 molar equivalents (with respect to the compound of formula (II)).
11. A process according to any one of the preceding claims, wherein the compound of formula (II) is used in an amount of at least 2 molar equivalents (with respect to the compound of formula (III)).
12. The process according to any one of the preceding claims, wherein the process according to the invention is generally carried out at a temperature of from -5°C to 120°C.