CA1173842A - Preparation of tocopheryl acetate and tocopheryl propionate - Google Patents
Preparation of tocopheryl acetate and tocopheryl propionateInfo
- Publication number
- CA1173842A CA1173842A CA000420769A CA420769A CA1173842A CA 1173842 A CA1173842 A CA 1173842A CA 000420769 A CA000420769 A CA 000420769A CA 420769 A CA420769 A CA 420769A CA 1173842 A CA1173842 A CA 1173842A
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- CA
- Canada
- Prior art keywords
- tocopheryl
- isophytol
- phytol
- reacted
- trimethylhydroquinone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/70—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with two hydrocarbon radicals attached in position 2 and elements other than carbon and hydrogen in position 6
- C07D311/72—3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrane Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
PREPARATION OF TOCOPHERYL ACETATE
AND TOCOPHERYL PROPIONATE
Abstract of the Disclosure Tocopheryl acetate or tocopheryl propionate is prepared by a process in which trimethylhydroquinone is reacted with phytol or isophytol in the presence of a proton donor and zinc chloride and of a liquid hydrocarbon as the solvent, the tocopherol obtained is then esterified, and the esterification mixture is worked up in a conventional manner to give tocopheryl acetate or tocopheryl propionate, wherein the mixture obtained in the reaction of trimethylhydroquinone with phytol or isophytol is cooled to room temperature, acetic anhydride or propionic anhydride is added and the resulting mixture is heated to 20-60°C or allowed to warm up to this temperature.
AND TOCOPHERYL PROPIONATE
Abstract of the Disclosure Tocopheryl acetate or tocopheryl propionate is prepared by a process in which trimethylhydroquinone is reacted with phytol or isophytol in the presence of a proton donor and zinc chloride and of a liquid hydrocarbon as the solvent, the tocopherol obtained is then esterified, and the esterification mixture is worked up in a conventional manner to give tocopheryl acetate or tocopheryl propionate, wherein the mixture obtained in the reaction of trimethylhydroquinone with phytol or isophytol is cooled to room temperature, acetic anhydride or propionic anhydride is added and the resulting mixture is heated to 20-60°C or allowed to warm up to this temperature.
Description
1~a'7~8~
Preparation of tocopheryl acetate and tocopheryl propionate The present invention reLates to an improved pro-cess for the preparation of tocopheryL acetate c~3 co-o~'J `l ~ ~ ~
by reacting trimethylhydroquinone with phytol or isophytol in the presence of a proton donor and zinc chloride and then esterifying the tocopherol ~ith acetic anhydride or propion;c anhydride.
Apart from the improvement according to the inven-tion, this process is kno~n in principle and in many variants, but the embodiments known hitherto are unsatis-factory.
According to ExampLe 1 of U.S. Patent 3,444,213, trimethylhydroquinone is condensed with isophytol in the presence of 3lacial acetic acid and BF3 etherate, the volat;le constituents are substantially separated off from the reaction mixture, and the crude tocopherol is heated ~ith acetic anhydride and pyridine. This procedure is relatively troubLesome and consumptive of energy, requires the presence of pyr;dine and in spite of this g;ves a yield of ~ocopheryl acetate of only 87X, uhich is unsatis-factory in view of the expensive starting materials.
A sinilar situation is found in the case of the ~.
l~t7~
prDcess described in U.5. Patent 3,708,505, in ~hich tri-~ethyihydroquinone is condensed ~ith isophytol in the presence of an scid and zinc chLoride ~nd of benzene as the diluent, and the reaction mixture is then subjected, at the boil, to an esterification reaction ~ith acetic anhydrideO Depending on the type of acid used, crude yieLds of tocopheryl acetate of from ~8 to 93.6Z are obtained in this c~se. Ho~ever, when the purities, ~hich ~re from b4 to 89.5X, ~re taken into account~ the yields of pure product are correspondingly lo~er. Moreover, the fact that the estcrification takes 6 hours at the boiling point constitutes a d;sadvantage.
~ apanese Patent 149,984 further~ore discloses that tocopheryl acetate ~ay ~e prepared by reacting toco-pherol uith acetic anhydride in the presence of hydrogen chloride ~nd zinc dust or cf zinc chloride. This reaction proceeds adiabatically, the temperature of the reaction ~ixture increas;n~ from room temper3ture to ~bo~t 60C~
takes about 1-2 hours ~nd gives a yield of ester of 96X~
b~sed on the d,l-a-tocopherol employed.
It is an object of the present invention to pre-p~re tocopheryl acetate fro~ triMe~hylhydroquinone and phytol or isGphytol in ~ ~anner ~hich is simpler and nore econo~ic~l than hitherto~
~ e h~ve found that ~hi~ object ~ aehieved ~nd that, surprisingly, the ~cetylation of tocopherol ~ith acetic anhydride in the presence of hydro~en chloride and 2inc dust or z;nr. ehloride ~lso proceeds virtuallr to com-pletion ~n ~ short ti~e ~nd ~ithou~ exterr~l heatin~ if, ~ 2 ~
3~
instead of using isolated and dry ~-tocopherol as a starting material, the two-phase dark mixture obtained in the reaction of trimethylhydroquinone with phytol or isophytol in the presence of a proton donor, preferably hydrogen chloride, and zinc chloride and of a liquid hydrocarbon is cooled and then reacted with acetic anhydride. After the addition of acetic anhydride has ended, the acetylation is virtually complete.
In this process, the tocopheryl acetate is obtained in good yield and, surprisingly, in very pure form.
Equally successful results were obtained in the preparation of tocopheryl propionate when the reaction mixture described was reacted with propionic anhydride.
The present invention accordigly relates to a process for the preparation of tocopheryl acetate or tocopheryl propionate by reacting trimethylhydroquinone with phytol or isophytol in the presence of a proton donor, zinc dust or - zinc chloride, and a liquid hydrocarbon as the solvent, esteri-fying the tocopherol obtai.ned and working up the esterification mixture to give tocopheryl acetate or tocopheryl propionate, wherein the mixture obtained in the reaction of trimethylhydro-quinone with phytol or isophytol is cooled and then reacted with acetic anhydride or propionic anhydride at from 0 to 60C.
In a particu].arly advantageous embodiment of the novel process, a mixture obtained by reacting trimethylhydro-quinone with phytol or is.ophytol while separating off water is reacted with acetic anhydride or propionic anhydride, at from 0 to 60C.
1~'7~3~
~he first step is advantageously carried out by ~radually adding phytol or isophytol to a mixture of tri-~ethylhydroquinone, the proton donor, z;nc chLor;de and the hydrocarbon at from 80 to 130C, and keeping the mix-ture uithin this temperature range for about 1-10 hours, uhiLe mixing thoroughly.
$n this process, the molar ratio of trimethyL-hydroquinone to phytol or isophytol is preferably from 0.9:1 to 1.1:1, and that of trimethylhydroquinone to zinc chloride is from 20:1 to 1:1.
About 0.5-2 liters of the hydrocarbon solvent are advantageously employed per moLe (152 9) of trimethyL-hydroquinone.
SuitabLe proton donDrs are strong mineraL acids, eg. hydrochloric acid, hydrogen chLor;de or suLfuric ac;d, strong acid saLts, eg. sodium hydrogen sulfate, and strong organic acids, eg. p-toluenesulfonic acid or tri-fluoroacetic acid, but hydrochloric acid or hydrogen chloride is preferably empLoyed.
Suitable solvents are hydrocarbons, eg. hexane, heptane, cyclohexane, benzene or toluene.
Since uater is split off in the condensation of trimethylhydroquinone ~ith phytol or isophytol, it is advisable to separat~ off continuously the ~ater formed and that already present in the reaction mixture. Although this is not absolutely netessary since the reattion proceeds smoothly even ~hen ~ater is not separated off, if this is not done a relatively large amount of carboxy~ic acid anhydride is required in the subsequent acylation step.
1~7;~
Furthermore, it may be advisable to carry out the reaction in a conventional manner in the presence of a small amount of a nitrogen base, such as ammonia or an organic amine, eg. stearylamine, or ~ith a phytol or iso-phytol ~h;ch has been treated at from 20 to 120C ~ith ammonia or an organic amine tcf. U.S. Patent 4,191,692 and German Patent 2,606,830).
After the condensat;on is complete, the reaction mixture obtained ;s cooled~ acetic anhydride or propionic anhydride is added at from 0 to 6ûC and if necessary the mixture is allo~ed to contin~e reacting for a further 0.5-3 hours at from 0 to 60C. ~orking up to give toco-pheryl acetate or tocopheryl propionate is then carried out in a convent;onal manner by extracting the mixture, for example ~ith water or aqueous methanol, and isolating the tocopheryl salt from the remaining hydrocarbon phase.
The acylation is exothermic, so that external heating of the reaction mixture is in general not necessary.
The carboxylic acid anhydride is advantageously added at from 20 to 50C, ~hile cooling ~ith ~ater. The acylation may also be carried out at a lo~er temperature, eg. ûC, but in ~eneral this has no substantial advan-tages, and the reaction nixSure must be cooled beforehand to the ~o~er temperature.
For the acylation step also, it is, surprisingly, not absolutely necessary that the ~ater formed in the con-densation of trimethylhydroquinone ~ith phytol or isophytol be removed from ~he reaction mixture either dur;ng or after the condensation. It ;s only necessary to add to the ~ ~'7~
reaction mixture a further molar amount of carboxylic acid anhydride equivaLent to the a~ount of ~ater present. For dry reaetion mixtures, in general from 1 to 1.5, preferably from 1.1 to 1.3, moles of carboxylic acid anhydride are required per mole of initially used trimethylhydroquinone, ~hereas for reaction mixtures for ~hich the ~ater of con-densation has not been remcved, from Z to 3, preferably from 2.1 to 2.5, moles are accordingly required. It is possible to use larger amounts of carboxylic acid anhy-dride, but this is of no further economic advantage. Even~hen ~ater of condensat;on is present in the reaction mixture, the acylation is virtually complete directly after the final amount of anhydride has been added, ie.
the content of free tocopherol is less than 0.1X (measured by high pressure column chromatography).
~ urthermore, essent;al features of the novel pro-cess are that the tocopherol formed in the condensation does not require to be isola~ed, and that the reaction mixture ob~ained in the condensation can be subjected to esterification, ~ithout further purification or process steps. In spite of this, the tocopheryl salt obtained in the novel process is, surprisingly, very pure. ~he car-boxylic ac;d anhydride residues ~hich in prior processes ~ere usually present in the product and ~ere difficult tv separate off are absent. Even from reaction mixtures in heptane, ~here the condensation has been carried out us;ng an excess of trimethylhydroquinone, a pure toco-pheryl saLt is obtained since the trimethyLhydroquinone is completely converted, for example in the reaction w;th ~IL7.~8~2 acetic anhydride, to trimethylhydroquinone diacetate, which can be readily extracted from the heptane solut;on using aqueous ~ethanol. This is very important since separation of tocopheryl acetate and trimethylhydroquinone diacetate by distillation ~ould be extremel~ difficult technically.
The process according to the invention gives very good quality tocopheryl acetate in a simple manner and in a yield of from 94 to 98X. ~he content of f ree tocopherol is less than 0.1X~
a) A mixture which contained 33.4 9 ~0.2 mole) of trimethylhydroquinone, 5 9 of zinc chloride, 0.5 9 of stearylamine and 250 ml of heptane and ~as saturated with hydrogen chloride gas ~as heated at the boil (98C~ while the HCl saturation uas ~aintained, 62.8 9 (0.21 mole) of isophytoL uere added in the course of one hour, and the mixture ~as kept at this temperature for a further hour.
b) The very dark, tvo-phase reaction mixture thus obtained ~as cooled to room temperature and 47 9 (û.46 mole) of acetic anhydride ~ere then added, the tem-perature being kept at 40C by ~ooling. The reaction mixture was cooled to room temperature and then extracted ~ith three times 200 ~l of a ~ixture of methano~ and ~ater ~1 1 V/V)r The remainin~ heptane phase ~as evaporated to dryness, and 96~1 ~ of pale yellow d~l-a-tocopheryl a~etate ~ith 8 purity of 93.0X ~ere obtained (USP XX), corres-pondin~ to a ~ieLd of 9~.5%, based on ~rimethylhydro-quinon~. The con~ent of free tocopherol was less than 1~7;~ 2 0.1% by veight according to HPLC. Distillation of the product gave 98Z pure tocophery~ acetate (USP X%).
~he procedure described in Example 1 ~as followed, except that the ~ater of reaction formed was additionally separated off in the first stage. Acetylation ~as carried out by adding 27 9 tO.27 mole) of acetic anhydride instead of 47 9 as stated in Example 1. The tocopheryl acetate ~as obtained in a purity of 94X and in a yield of 98Z (USP-XX).
The procedure descr;bed ir, Example 1a) was followed~ and the reaction mixture obta;ned was then cooled to ûC instead of room temperature. 47 9 (0.46 mole) of acetic anhydride ~ere then added at 0C in the course of 20 m;nutes, ~hile stirring, the mixture was extracted ~ith three times 20û ml of a 1:1 m;xture of ~ethanol and ~ater, and the remaining heptane phase ~as then evaporated to dryness. 96 9 of 94% pure tocopheryl acetate ~ere obtained, corresponding to a yield of 95%.
The purity of the distilled product ~as 97X.
The procedure descr;bed in Example 1a) ~as follo~ed, except Shat 38 ~ ~0.25 mole) of trimethylhydro-quinone were employed ins~ead of 30.4 ~ S0.2 mole).
57.2 9 (0.56 moLe) of acetic anh~dride were edded at room temperatur~ to the reaction mixture obtained, the tempera-ture increasin~ to 55C, and the mixture ~as then extracted three t;mes with 90% strength aqueous methanol 3~
and once ~ith 75Z strength methanoL. 95.8 9 of 94.9% pure tocopheryl acetate ~ere obtained, corresponding to a yield of 96.2X, based on the 97X strength isophytol employed.
It ~as possible to distil the tocopheryl acetate without difficuLty~ since the product obtained no longer conta;ns any trimethylhydroquinone diacetat 2 . The purity of the distilled product was 97.2X 5USP XX).
The procedure described in Example la) ~as follo~ed. The dark t~o-phase reaction mixture obtained in this condensation uas cooled to room temperature, after ~hich 59.9 9 (0.46 mole) of propionic anhydride ~ere added, the temperature increasing to 50C. The reaction mixture was allo~ed to cool to room temperature and then extracted with three times 200 ml of a methanol/uater mix-ture (1:1 v/v), and the remaining heptane phase ~as evaporated to dryness. 101.Z g of paLe ~ello~ d,l-~-toco-pheryl propionate u;th a purity of 90.5X ~gas chroma-tosraphy) uere obtained, corresponding to a yield of 94.1%, based on trimethylhydroquinone employed. The content of free tocopherol ~as less than 0.1X by ~eight according to HPLC. Distillation of the product gave 95.2% pure toco-pheryl propionate.
g _
Preparation of tocopheryl acetate and tocopheryl propionate The present invention reLates to an improved pro-cess for the preparation of tocopheryL acetate c~3 co-o~'J `l ~ ~ ~
by reacting trimethylhydroquinone with phytol or isophytol in the presence of a proton donor and zinc chloride and then esterifying the tocopherol ~ith acetic anhydride or propion;c anhydride.
Apart from the improvement according to the inven-tion, this process is kno~n in principle and in many variants, but the embodiments known hitherto are unsatis-factory.
According to ExampLe 1 of U.S. Patent 3,444,213, trimethylhydroquinone is condensed with isophytol in the presence of 3lacial acetic acid and BF3 etherate, the volat;le constituents are substantially separated off from the reaction mixture, and the crude tocopherol is heated ~ith acetic anhydride and pyridine. This procedure is relatively troubLesome and consumptive of energy, requires the presence of pyr;dine and in spite of this g;ves a yield of ~ocopheryl acetate of only 87X, uhich is unsatis-factory in view of the expensive starting materials.
A sinilar situation is found in the case of the ~.
l~t7~
prDcess described in U.5. Patent 3,708,505, in ~hich tri-~ethyihydroquinone is condensed ~ith isophytol in the presence of an scid and zinc chLoride ~nd of benzene as the diluent, and the reaction mixture is then subjected, at the boil, to an esterification reaction ~ith acetic anhydrideO Depending on the type of acid used, crude yieLds of tocopheryl acetate of from ~8 to 93.6Z are obtained in this c~se. Ho~ever, when the purities, ~hich ~re from b4 to 89.5X, ~re taken into account~ the yields of pure product are correspondingly lo~er. Moreover, the fact that the estcrification takes 6 hours at the boiling point constitutes a d;sadvantage.
~ apanese Patent 149,984 further~ore discloses that tocopheryl acetate ~ay ~e prepared by reacting toco-pherol uith acetic anhydride in the presence of hydrogen chloride ~nd zinc dust or cf zinc chloride. This reaction proceeds adiabatically, the temperature of the reaction ~ixture increas;n~ from room temper3ture to ~bo~t 60C~
takes about 1-2 hours ~nd gives a yield of ester of 96X~
b~sed on the d,l-a-tocopherol employed.
It is an object of the present invention to pre-p~re tocopheryl acetate fro~ triMe~hylhydroquinone and phytol or isGphytol in ~ ~anner ~hich is simpler and nore econo~ic~l than hitherto~
~ e h~ve found that ~hi~ object ~ aehieved ~nd that, surprisingly, the ~cetylation of tocopherol ~ith acetic anhydride in the presence of hydro~en chloride and 2inc dust or z;nr. ehloride ~lso proceeds virtuallr to com-pletion ~n ~ short ti~e ~nd ~ithou~ exterr~l heatin~ if, ~ 2 ~
3~
instead of using isolated and dry ~-tocopherol as a starting material, the two-phase dark mixture obtained in the reaction of trimethylhydroquinone with phytol or isophytol in the presence of a proton donor, preferably hydrogen chloride, and zinc chloride and of a liquid hydrocarbon is cooled and then reacted with acetic anhydride. After the addition of acetic anhydride has ended, the acetylation is virtually complete.
In this process, the tocopheryl acetate is obtained in good yield and, surprisingly, in very pure form.
Equally successful results were obtained in the preparation of tocopheryl propionate when the reaction mixture described was reacted with propionic anhydride.
The present invention accordigly relates to a process for the preparation of tocopheryl acetate or tocopheryl propionate by reacting trimethylhydroquinone with phytol or isophytol in the presence of a proton donor, zinc dust or - zinc chloride, and a liquid hydrocarbon as the solvent, esteri-fying the tocopherol obtai.ned and working up the esterification mixture to give tocopheryl acetate or tocopheryl propionate, wherein the mixture obtained in the reaction of trimethylhydro-quinone with phytol or isophytol is cooled and then reacted with acetic anhydride or propionic anhydride at from 0 to 60C.
In a particu].arly advantageous embodiment of the novel process, a mixture obtained by reacting trimethylhydro-quinone with phytol or is.ophytol while separating off water is reacted with acetic anhydride or propionic anhydride, at from 0 to 60C.
1~'7~3~
~he first step is advantageously carried out by ~radually adding phytol or isophytol to a mixture of tri-~ethylhydroquinone, the proton donor, z;nc chLor;de and the hydrocarbon at from 80 to 130C, and keeping the mix-ture uithin this temperature range for about 1-10 hours, uhiLe mixing thoroughly.
$n this process, the molar ratio of trimethyL-hydroquinone to phytol or isophytol is preferably from 0.9:1 to 1.1:1, and that of trimethylhydroquinone to zinc chloride is from 20:1 to 1:1.
About 0.5-2 liters of the hydrocarbon solvent are advantageously employed per moLe (152 9) of trimethyL-hydroquinone.
SuitabLe proton donDrs are strong mineraL acids, eg. hydrochloric acid, hydrogen chLor;de or suLfuric ac;d, strong acid saLts, eg. sodium hydrogen sulfate, and strong organic acids, eg. p-toluenesulfonic acid or tri-fluoroacetic acid, but hydrochloric acid or hydrogen chloride is preferably empLoyed.
Suitable solvents are hydrocarbons, eg. hexane, heptane, cyclohexane, benzene or toluene.
Since uater is split off in the condensation of trimethylhydroquinone ~ith phytol or isophytol, it is advisable to separat~ off continuously the ~ater formed and that already present in the reaction mixture. Although this is not absolutely netessary since the reattion proceeds smoothly even ~hen ~ater is not separated off, if this is not done a relatively large amount of carboxy~ic acid anhydride is required in the subsequent acylation step.
1~7;~
Furthermore, it may be advisable to carry out the reaction in a conventional manner in the presence of a small amount of a nitrogen base, such as ammonia or an organic amine, eg. stearylamine, or ~ith a phytol or iso-phytol ~h;ch has been treated at from 20 to 120C ~ith ammonia or an organic amine tcf. U.S. Patent 4,191,692 and German Patent 2,606,830).
After the condensat;on is complete, the reaction mixture obtained ;s cooled~ acetic anhydride or propionic anhydride is added at from 0 to 6ûC and if necessary the mixture is allo~ed to contin~e reacting for a further 0.5-3 hours at from 0 to 60C. ~orking up to give toco-pheryl acetate or tocopheryl propionate is then carried out in a convent;onal manner by extracting the mixture, for example ~ith water or aqueous methanol, and isolating the tocopheryl salt from the remaining hydrocarbon phase.
The acylation is exothermic, so that external heating of the reaction mixture is in general not necessary.
The carboxylic acid anhydride is advantageously added at from 20 to 50C, ~hile cooling ~ith ~ater. The acylation may also be carried out at a lo~er temperature, eg. ûC, but in ~eneral this has no substantial advan-tages, and the reaction nixSure must be cooled beforehand to the ~o~er temperature.
For the acylation step also, it is, surprisingly, not absolutely necessary that the ~ater formed in the con-densation of trimethylhydroquinone ~ith phytol or isophytol be removed from ~he reaction mixture either dur;ng or after the condensation. It ;s only necessary to add to the ~ ~'7~
reaction mixture a further molar amount of carboxylic acid anhydride equivaLent to the a~ount of ~ater present. For dry reaetion mixtures, in general from 1 to 1.5, preferably from 1.1 to 1.3, moles of carboxylic acid anhydride are required per mole of initially used trimethylhydroquinone, ~hereas for reaction mixtures for ~hich the ~ater of con-densation has not been remcved, from Z to 3, preferably from 2.1 to 2.5, moles are accordingly required. It is possible to use larger amounts of carboxylic acid anhy-dride, but this is of no further economic advantage. Even~hen ~ater of condensat;on is present in the reaction mixture, the acylation is virtually complete directly after the final amount of anhydride has been added, ie.
the content of free tocopherol is less than 0.1X (measured by high pressure column chromatography).
~ urthermore, essent;al features of the novel pro-cess are that the tocopherol formed in the condensation does not require to be isola~ed, and that the reaction mixture ob~ained in the condensation can be subjected to esterification, ~ithout further purification or process steps. In spite of this, the tocopheryl salt obtained in the novel process is, surprisingly, very pure. ~he car-boxylic ac;d anhydride residues ~hich in prior processes ~ere usually present in the product and ~ere difficult tv separate off are absent. Even from reaction mixtures in heptane, ~here the condensation has been carried out us;ng an excess of trimethylhydroquinone, a pure toco-pheryl saLt is obtained since the trimethyLhydroquinone is completely converted, for example in the reaction w;th ~IL7.~8~2 acetic anhydride, to trimethylhydroquinone diacetate, which can be readily extracted from the heptane solut;on using aqueous ~ethanol. This is very important since separation of tocopheryl acetate and trimethylhydroquinone diacetate by distillation ~ould be extremel~ difficult technically.
The process according to the invention gives very good quality tocopheryl acetate in a simple manner and in a yield of from 94 to 98X. ~he content of f ree tocopherol is less than 0.1X~
a) A mixture which contained 33.4 9 ~0.2 mole) of trimethylhydroquinone, 5 9 of zinc chloride, 0.5 9 of stearylamine and 250 ml of heptane and ~as saturated with hydrogen chloride gas ~as heated at the boil (98C~ while the HCl saturation uas ~aintained, 62.8 9 (0.21 mole) of isophytoL uere added in the course of one hour, and the mixture ~as kept at this temperature for a further hour.
b) The very dark, tvo-phase reaction mixture thus obtained ~as cooled to room temperature and 47 9 (û.46 mole) of acetic anhydride ~ere then added, the tem-perature being kept at 40C by ~ooling. The reaction mixture was cooled to room temperature and then extracted ~ith three times 200 ~l of a ~ixture of methano~ and ~ater ~1 1 V/V)r The remainin~ heptane phase ~as evaporated to dryness, and 96~1 ~ of pale yellow d~l-a-tocopheryl a~etate ~ith 8 purity of 93.0X ~ere obtained (USP XX), corres-pondin~ to a ~ieLd of 9~.5%, based on ~rimethylhydro-quinon~. The con~ent of free tocopherol was less than 1~7;~ 2 0.1% by veight according to HPLC. Distillation of the product gave 98Z pure tocophery~ acetate (USP X%).
~he procedure described in Example 1 ~as followed, except that the ~ater of reaction formed was additionally separated off in the first stage. Acetylation ~as carried out by adding 27 9 tO.27 mole) of acetic anhydride instead of 47 9 as stated in Example 1. The tocopheryl acetate ~as obtained in a purity of 94X and in a yield of 98Z (USP-XX).
The procedure descr;bed ir, Example 1a) was followed~ and the reaction mixture obta;ned was then cooled to ûC instead of room temperature. 47 9 (0.46 mole) of acetic anhydride ~ere then added at 0C in the course of 20 m;nutes, ~hile stirring, the mixture was extracted ~ith three times 20û ml of a 1:1 m;xture of ~ethanol and ~ater, and the remaining heptane phase ~as then evaporated to dryness. 96 9 of 94% pure tocopheryl acetate ~ere obtained, corresponding to a yield of 95%.
The purity of the distilled product ~as 97X.
The procedure descr;bed in Example 1a) ~as follo~ed, except Shat 38 ~ ~0.25 mole) of trimethylhydro-quinone were employed ins~ead of 30.4 ~ S0.2 mole).
57.2 9 (0.56 moLe) of acetic anh~dride were edded at room temperatur~ to the reaction mixture obtained, the tempera-ture increasin~ to 55C, and the mixture ~as then extracted three t;mes with 90% strength aqueous methanol 3~
and once ~ith 75Z strength methanoL. 95.8 9 of 94.9% pure tocopheryl acetate ~ere obtained, corresponding to a yield of 96.2X, based on the 97X strength isophytol employed.
It ~as possible to distil the tocopheryl acetate without difficuLty~ since the product obtained no longer conta;ns any trimethylhydroquinone diacetat 2 . The purity of the distilled product was 97.2X 5USP XX).
The procedure described in Example la) ~as follo~ed. The dark t~o-phase reaction mixture obtained in this condensation uas cooled to room temperature, after ~hich 59.9 9 (0.46 mole) of propionic anhydride ~ere added, the temperature increasing to 50C. The reaction mixture was allo~ed to cool to room temperature and then extracted with three times 200 ml of a methanol/uater mix-ture (1:1 v/v), and the remaining heptane phase ~as evaporated to dryness. 101.Z g of paLe ~ello~ d,l-~-toco-pheryl propionate u;th a purity of 90.5X ~gas chroma-tosraphy) uere obtained, corresponding to a yield of 94.1%, based on trimethylhydroquinone employed. The content of free tocopherol ~as less than 0.1X by ~eight according to HPLC. Distillation of the product gave 95.2% pure toco-pheryl propionate.
g _
Claims (12)
1. A process for the preparation of tocopheryl acetate or tocopheryl propionate by reacting trimethylhydroquinone with phytol or isophytol in the presence of a proton donor, zinc dust or zinc chloride, and a liquid hydrocarbon as the solvent, esterifying the tocopherol obtained and working up the esteri-fication mixture to give tocopheryl acetate or tocopheryl pro-pionate, wherein the mixture obtained in the reaction of tri-methylhydroquinone with phytol or isophytol is cooled and then reacted with acetic anhydride or propionic anhydride at from 0 to 60°C.
2. A process as claimed in claim 1, wherein a mixture obtained by reacting trimethylhydroquinone with phytol or isophytol while separating off water is reacted with acetic anhydride or propionic anhydride, at from 0 to 60°C.
3. The process of claim 1 wherein the mixture obtained by reacting trimethylhydroquinone with phytol or isophytol is cooled to room temperature and then reacted with acetic anhydride or propionic anhydride at 20 to 60°C.
4. The process of either of claims 1 or 2 wherein said proton donor is at least one of hydrogen chloride gas, a strong mineral acid or a strong acid salt.
5. The process of either of claims 1 or 2 wherein said proton donor is selected from the group consisting of hydrogen chloride gas, hydrochloric acid, and sulfuric acid.
6. The process of either of claims 1 or 2 wherein said liquid hydrocarbon is selected from the group consisting of at least one of hexane, heptane, cyclohexane, benzene and toluene.
7. A process for the preparation of tocopheryl acetate or tocopheryl propionate by reacting trimethylhydroquinone with phytol or isophytol in the presence of a proton donor, zinc chloride, and a liquid hydrocarbon as the solvent, esterifying the tocopherol obtained and working up the esterification mixture to give tocopheryl acetate or tocopheryl propionate, wherein the mixture obtained in the reaction of trimethyl-hydroquinone with phytol or isophytol is cooled and then reacted with acetic anhydride or propionic anhydride at from 0 to 60°C.
8. A process as claimed in claim 7, wherein a mixture obtained by reacting trimethylhydroquinone with phytol or isophytol while separating off water is reacted with acetic anhydride or propionic anhydride, at from 0 to 60°C.
9. The process of claim 7 wherein the mixture obtained by reacting trimethylhydroquinone with phytol or isophytol is cooled to room temperature and then reacted with acetic anhydride or propionic anhydride at 20 to 60°C.
10. The process of either of claims 7 or 8 wherein said proton donor is at least one of hydrogen chloride gas, a strong mineral acid or a strong acid salt.
11. The process of either of claims 7 or 8 wherein said proton donor is selected from the group consisting of hydrogen chloride gas, hydrochloric acid, and sulfuric acid.
12. The process of either of claims 7 or 8 wherein said liquid hydrocarbon is selected from the group consisting of at least one of hexane, heptane, cyclohexane, benzene and toluene.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3203487.3 | 1982-02-03 | ||
| DE19823203487 DE3203487A1 (en) | 1982-02-03 | 1982-02-03 | METHOD FOR PRODUCING TOCOPHERYL ACETATE OR TOCOPHERYL PROPIONATE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1173842A true CA1173842A (en) | 1984-09-04 |
Family
ID=6154593
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000420769A Expired CA1173842A (en) | 1982-02-03 | 1983-02-02 | Preparation of tocopheryl acetate and tocopheryl propionate |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP0087576B1 (en) |
| CA (1) | CA1173842A (en) |
| DE (2) | DE3203487A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3367100D1 (en) * | 1982-07-29 | 1986-11-27 | Basf Wyandotte Corp | Alpha tocopherol process |
| US6005122A (en) * | 1996-12-23 | 1999-12-21 | Basf Aktiengesellschaft | Preparation of α-tocopherol or α-tocopheryl acetate by reacting trimethylhydroquinone and phytol or isophytol, with recycling of the zinc halide condensation catalyst |
| FR2784104B1 (en) | 1998-09-18 | 2002-12-27 | Rhone Poulenc Nutrition Animal | PROCESS FOR THE PREPARATION OF VITAMIN E |
| DE10011403A1 (en) * | 2000-03-09 | 2001-09-13 | Degussa | Production of alpha-tocopherol acetate useful as feed additive involves condensation of trimethylhydroquinone and isophytol in presence of a regenerable catalyst system followed by acylation of the resultant alpha-tocopherol |
| EP1663937A2 (en) * | 2003-09-15 | 2006-06-07 | DSM IP Assets B.V. | Synthesis of alpha-tocopheryl alkanoates and precursors thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3708505A (en) * | 1971-02-25 | 1973-01-02 | Diamond Shamrock Corp | Process for preparation of d,l-alpha tocopherol |
| DE2606830C3 (en) * | 1976-02-20 | 1981-08-27 | Basf Ag, 6700 Ludwigshafen | Process for the production of tocopherol |
| JPS6019309B2 (en) * | 1976-09-29 | 1985-05-15 | 日清製粉株式会社 | Production method of high purity dl-α-tocopherol |
-
1982
- 1982-02-03 DE DE19823203487 patent/DE3203487A1/en not_active Withdrawn
-
1983
- 1983-01-22 EP EP83100571A patent/EP0087576B1/en not_active Expired
- 1983-01-22 DE DE8383100571T patent/DE3367775D1/en not_active Expired
- 1983-02-02 CA CA000420769A patent/CA1173842A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| EP0087576A1 (en) | 1983-09-07 |
| EP0087576B1 (en) | 1986-11-20 |
| DE3367775D1 (en) | 1987-01-08 |
| DE3203487A1 (en) | 1983-08-11 |
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