Preparation of tocopherols

The invention provides methods for producing tocopherol compounds of the Vitamin E family by reduction of various 4-chromanone trienol materials. In preferred embodiments the invention provides methods of preparing and hydrogenating 4-chromanone trienols to provide gamma-tocopherol.

FIELD OF THE INVENTION
 This invention relates generally processes for producing vitamin E and
 related compounds. In particular, the invention relates to processes for
 producing tocopherols and certain tocopherol derivatives, including gamma
 ##STR1##
 1=d-tocopherols
 1a=d-alpha tocopherol R.sub.1.dbd.R.sub.2.dbd.R.sub.3.dbd.CH.sub.3
 1b=d-beta tocopherol R.sub.1.dbd.R.sub.3.dbd.CH.sub.3, R.sub.2.dbd.H
 1c=d-gamma tocopherol R.sub.1.dbd.H, R.sub.2.dbd.R.sub.3.dbd.CH.sub.3
 1d=d-delta tocopherol R.sub.1.dbd.R.sub.2.dbd.H, R.sub.3.dbd.CH.sub.3
 tocopherol.
 BACKGROUND OF THE INVENTION
 The naturally occurring vitamin E family of compounds includes a number of
 homologous tocopherols 1, and tocotrienols 2.
 ##STR2##
 These compounds differ in the number and position of aromatic ring methyl
 groups, and in the degree of side chain unsaturation.
 Naturally occurring vitamin E (d-alpha-tocopherol, 1a) is an important
 nutritional supplement in humans and animals, and is obtained commercially
 by isolation from a variety of plant oils, or semi-synthetically by ring
 methylation of less-substituted tocopherol compounds, such as the related
 naturally occurring d-gamma-tocopherol 1b. An important source of
 tocopherols is chemical synthesis, which provides d,l-alpha-tocopherol, 3.
 Commercially available samples of 3 are typically composed of mixtures of
 optical isomers at the 2, 4', and 8' positions,
 ##STR3##
 D,L-gamma tocopherol, 4, differs from 3 only by the presence or absence of
 a 5-methyl substituent on the aromatic ring.
 ##STR4##
 3 and 4 provide much of the biological activity of 1a, and are widely used
 due to lower cost and greater availability. The other tocopherols have
 also been shown to possess important antioxidant or vitamin E activity in
 mammals and humans, and are included in many modern commercial nutritional
 supplements. For a general discussion of vitamin E chemistry, see L.
 Machlin, ed., "Vitamin E: A Comprehensive Treatise", Marcel Dekker, NY,
 1980.
 It is known that d,l-alpha-tocopherol 3 is obtained by reacting
 trimethylhydroquinone with either phytol or isophytol in the presence of
 an acid. Other known technologies for preparation of tocopherols and
 tocotrienols were reviewed by S. Kasparek in chapter 2 of Machlin's
 Treatise, pp. 8-65. References 140-166 of Kasparek's chapter provide the
 primary references to other methods of preparing compound 3.
 Kabbe and Heitzer reported a multi-step synthesis of d,l-alpha-tocopherol,
 3, (Synthesis 888, 1978). Two known compounds,
 (2-acetyl-3,5,6-trimethylhydroquinone and farnesylacetone 5) were
 condensed to give a 4-chromanone tocotrienol compound 6, whose structure
 is shown in Scheme 1 below.
 ##STR5##
 The 4-keto group of compound 6 was (a) reduced with sodium borohydride to
 give the corresponding alcohol, (b) the alcohol was dehydrated to give the
 tetra-olefin, and (c) the four carbon-carbon double bonds of the
 tetra-olefin were hydrogenated to give d,l-alpha-tocopherol 3. Kabbe
 et.al.'s multi-step process to produce alpha tocopherol from a
 4-chromanone trienol is industrially undesirable however, because
 stoichiometric quantities of expensive borohydride reagents are consumed
 and undesirable borate wastes are formed, multiple reaction steps and
 solvents are employed, and equipment and operational costs are high. Kabbe
 et.al. made no suggestion that a simpler process could be employed.
 The multi-step sequence is apparently necessary, at least in the case of
 preparation of alpha-tocopherol. The current inventors have found that the
 tri-methyl-4-chromanone compound 6, is not detectably converted to
 alpha-tocopherol by direct catalytic hydrogenation. Attempts to carry out
 direct hydrogenation of compound 6, (as illustrated in Scheme 2 and
 described in Comparative Example 1) have led instead to formation of a
 saturated ketone, 7. No further hydrogenation of 7 occurs, and no
 detectible quantity of 3 is produced.
 ##STR6##
 In the "gamma" series of compounds (i.e. 7,8-dimethyl tocopherols and
 tocotrienols), gamma tocopherol, 4, was first chemically synthesized by
 Jacob, Steiger, Todd and Wilcox (J. Chem. Soc. 1939, 542) by reacting the
 monobenzoate ester of 2,3-dimethylhydroquinone with phytyl bromide in the
 presence of zinc chloride, followed by removal of the benzoate to give a
 low yield (22%) of gamma-tocopherol. More recently, U.S. Pat. No.
 5,591,772 to Lane, Qureshi, and Salser reported isolation of the
 7,8-dimethyl-4-chromanone trienol compound 8 (whose structure is shown in
 Scheme 3) from natural sources.
 ##STR7##
 Pearce et al. (J. Med. Chem. 37, 526-541, 1994) adapted the method of Kabbe
 and Heitzer to synthesize compound 8 in racemic form and partially reduce
 it. See Scheme 3. 2-Acetyl-5,6-dimethyl-hydroquinone, 9, and
 farnesylacetone, 5, were condensed to give compound 8, then the 4-keto
 group of 8 was chemically reduced and removed with stoichiometric
 quantities of aluminum hydride reagents, to give the gamma-tocotrienol
 derivative 10. Lane et. al. and Pearce et.al. did not suggest a process
 for converting the 4-chromanone compound 8 to gamma tocopherol 4.
 Conversion of compound 8 to compound 10 with aluminum hydrides, then to
 gamma-tocopherol, compound 4, would require additional reduction steps and
 have many of the disadvantages of Kabbe's process for the production of
 alpha-tocopherol.
 Thus, despite the various known methods for preparing or isolating
 compounds related to the vitamin E family of compounds, there remains a
 need for simpler and more efficient methods of production of tocopherol
 derivatives.
 SUMMARY OF THE INVENTION
 In accordance with the purpose(s) of this invention, as embodied and
 broadly described herein, this invention, in one aspect, relates to a
 process for preparing a tocopherol compound, comprising reducing a
 4-chromanone trienol material
 ##STR8##
 in the presence of at least one hydrogen donor and a catalyst, under
 conditions and for a time sufficient to form at least some of a tocopherol
 compound
 ##STR9##
 wherein R.sub.2 and R.sub.3 are methyl or hydrogen, and PG is hydrogen or a
 removable protecting group.
 The invention further provides a process for preparing gamma-tocopherol by
 hydrogenation, comprising reacting
 ##STR10##
 and H.sub.2 at a pressure from about 400 to about 750 psig; in a reactor
 containing a solvent and a Raney nickel catalyst, at a temperature from
 about 135.degree. C. to about 200.degree. C., for a time from about 1 to
 about 10 hours.
 In view of Kabbe et.al.'s failure to suggest direct hydrogenation of the
 4-chromanone compound 6 to produce alpha-tocopherol, and the failure of
 attempts by the current inventors to produce alpha-tocopherol by direct
 hydrogenation of 6, it is particularly unexpected and surprising that
 gamma tocopherol, which differs from alpha-tocopherol only by the absence
 of a methyl group at the 5-position of the aromatic ring, can be produced
 in very high yield by the instant methods.
 Additional advantages of the invention will be set forth in part in the
 description which follows, and in part will be obvious from the
 description, or may be learned by practice of the invention. The
 advantages of the invention will be realized and attained by means of the
 elements and combinations particularly pointed out in the appended claims.
 It is to be understood that both the foregoing general description and the
 following detailed description are exemplary and explanatory only and are
 not restrictive of the invention, as claimed.
 DESCRIPTION OF THE PREFERRED EMBODIMENTS
 The present invention may be understood more readily by reference to the
 following detailed description of preferred embodiments of the invention
 and the examples included therein.
 Definitions and Use of Terms
 Before the present compounds, compositions and methods are disclosed and
 described, it is to be understood that the terminology used herein is for
 the purpose of describing particular embodiments only and is not intended
 to be limiting.
 It must be noted that, as used in the specification and the appended
 claims, the singular forms "a," "an" and "the" include plural referents
 unless the context clearly dictates otherwise. Thus, for example,
 reference to "an aromatic compound" includes mixtures of aromatic
 compounds, reference to "a pharmaceutical carrier" includes mixtures of
 two or more such carriers, and the like.
 Ranges are often expressed herein as from "about" one particular value,
 and/or to "about" another particular value. When such a range is
 expressed, another embodiment includes from the one particular value
 and/or to the other particular value. Similarly, when values are expressed
 as approximations, by use of the antecedent "about," it will be understood
 that the particular value forms another embodiment. It will be further
 understood that the endpoints of each of the ranges are significant both
 in relation to the other endpoint, and independently of the other
 endpoint.
 In this specification and in the claims which follow, reference will be
 made to a number of terms which shall be defined to have the following
 meanings:
 A protecting group (PG) is defined for the purposes of this invention as a
 substituent group which can be chemically bound to a phenolic oxygen atom,
 and subsequently removed (either chemically, in-vitro, or in-vivo) from
 the phenolic oxygen atom by predictable methods. Examples of many of the
 possible protective groups can be found in Protective Groups in Organic
 Synthesis by T. W. Green, John Wiley and Sons, 1981, pp. 10-86, which is
 incorporated herein by reference in its entirety.
 A reducing agent is defined for the purposes of this invention as any
 device, chemical compound, or composition which is capable of donating or
 transferring one or more electrons to another chemical compound or
 composition. A reducing agent may or may not also donate hydrogen nucleii
 to the other chemical composition.
 A hydrogen donor is defined for the purposes of this invention as a
 chemical compound or composition which is capable of donating or
 transferring a hydrogen nucleus to a chemical compound or composition
 which is being reduced. A hydrogen donor may or may not also donate
 electrons to the chemical compound or composition. The hydrogen donors may
 donate or transfer the hydrogen nuclei to another chemical compound or
 composition in association with various numbers of electrons (including
 acidic hydrogen, H.sup.+, with no associated electrons; neutral hydrogen,
 as H.sup..multidot., H-Donor, or H.sub.2, wherein the donor provides
 approximately one associated electron per hydrogen nucleus; or as hydridic
 hydrogen, H.sup.-, having approximately two associated electrons per
 hydrogen nucleus).
 The terms "alkene" or "olefin" as used herein intends a carbon-containing
 compound or functional group of 2 to 24 carbon atoms having 1 to 4
 carbon-carbon double bonds, excluding any carbon-carbon double bonds which
 are part of an aromatic ring. Preferred alkene or olefing groups within
 this class contain 2 to 12 carbon atoms. Asymmetric structures such as
 (AB)C.dbd.C(CD) are intended to include both the E and Z isomers. This may
 be presumed in structural formulae herein wherein an asymmetric alkene is
 present, or it may be explicitly indicated by the bond symbol .dbd..
 A residue of a chemical species, as used in the specification and
 concluding claims, refers to the moiety that is the resulting product of
 the chemical species in a particular reaction scheme or subsequent
 formulation or chemical product, regardless of whether the moiety is
 actually obtained from the chemical species. Thus, an ethylene glycol
 residue in a polyester refers to one or more --OCH.sub.2 CH.sub.2 O--
 units in the polyester, regardless of whether ethylene glycol was used to
 prepare the polyester. Similarly, a phenolic residue in a compound refers
 to one or more aryl groups having an oxygen singly bonded to a carbon atom
 which is part of an aryl ring, regardless of whether the residue is
 obtained by reacting phenol or an ester thereof to obtain the compound.
 References in the specification and concluding claims to parts by weight,
 of a particular element or component in a composition or article, denotes
 the weight relationship between the element or component and any other
 elements or components in the composition or article for which a part by
 weight is expressed. Thus, in a compound containing 2 parts by weight of
 component X and 5 parts by weight component Y, X and Y are present at a
 weight ratio of 2:5, and are present in such ratio regardless of whether
 additional components are contained in the compound.
 A weight percent of a component, unless specifically stated to the
 contrary, is based on the total weight of the formulation or composition
 in which the component is included.
 "Optional" or "optionally" means that the subsequently described event or
 circumstance may or may not occur, and that the description includes
 instances where said event or circumstance occurs and instances where it
 does not. For example, the phrase "optionally substituted lower alkyl"
 means that the lower alkyl group may or may not be substituted and that
 the description includes both unsubstituted lower alkyl and lower alkyl
 where there is substitution.
 By the term "effective amount" of a compound or property as provided herein
 is meant such amount as is capable of performing the function of the
 compound or property for which an effective amount is expressed. As will
 be pointed out below, the exact amount required will vary from process to
 process, depending on recognized variables such as the compounds employed
 and the processing conditions observed. Thus, it is not possible to
 specify an exact "effective amount." However, an appropriate effective
 amount may be determined by one of ordinary skill in the art using only
 routine experimentation.
 Discussion
 The present invention provides a process for preparing a tocopherol
 compound, comprising reducing a 4-chromanone trienol material
 ##STR11##
 in the presence of at least one hydrogen donor and a catalyst, under
 conditions and for a time sufficient to form at least some of a tocopherol
 compound
 ##STR12##
 wherein R.sub.2 and R.sub.3 are methyl or hydrogen, and PG is hydrogen or a
 protecting group. The tocopherol compound may have any combination of
 optical isomers at the 2, 4', and 8' carbon atoms.
 In one preferred embodiment, the protecting group and the oxygen bonded to
 the protecting group forms a C.sub.2 -C.sub.25 ester group. In these
 embodiments, the protecting group comprises the acyl portion of a
 carboxylic acid. The acyl portion of the carboxylic acid may be derived
 from a C.sub.2 -C.sub.25 carboxylic acid, or preferably a C.sub.2
 -C.sub.12 carboxylic acid. Examples of the ester groups which can be
 formed include but are not limited to an acetic acid ester group, a
 propionic acid ester group, a succinic acid ester group, benzoic acid
 ester groups, fatty acid ester groups, esters of amino acids, and the
 like.
 In certain preferred embodiments the 4-chromanone trienol material
 comprises
 ##STR13##
 and the tocopherol compound comprises
 ##STR14##
 In the above processes of the invention, the 4-chromanone trienol materials
 are reduced in the presence of at least one hydrogen donor and at least
 one catalyst. In particular, the three carbon-carbon double bonds and the
 carbon-oxygen double bond of the 4-chromanone trienol material are
 reduced. The carbon-carbon double bonds and the carbon-oxygen double bond
 may be reduced in any sequence or order. The reduction steps may be
 preceded by substitution of the starting material to form chemical
 intermediates with a variety of heteroatomic substituent groups. Chemical
 intermediates having various substituents bonded to the 4-chromanone
 trienol carbon skeleton (either transitory and stable) may be involved
 during the process of reducing. Preferably, all the carbon-carbon and
 carbon-oxygen double bonds are concurrently reduced via a single reducing
 method.
 At some point during the process of reducing, the carbon atoms having
 double bonds to be reduced are provided with new carbon-hydrogen bonds.
 Therefore, the reducing process requires at least one hydrogen donor, to
 provide the required hydrogen nucleii. During the process of reducing, a
 source of electrons must also be supplied by a reducing agent. The
 hydrogen donor may or may not also function as the reducing agent, to
 supply the required electrons. In many embodiments, the hydrogen donor
 does supplies electrons for the reduction step, and functions as a
 reducing agent. If the hydrogen donor does not supply electrons for the
 reduction step, a separate reducing agent must be provided to supply
 electrons for the reducing step. A plurality of reducing agents, or
 hydrogen donors, or mixtures of reducing agents and hydrogen donors can be
 utilized. More preferably, the reducing occurs in the presence a single
 hydrogen donor, which also supplies electrons, and therefore no separate
 reducing agent is required.
 In another preferred embodiment of the process, the reducing is by
 hydrogenation. Hydrogenation is defined for the purposes of this invention
 as a process of reducing in which a double bond is replaced by two carbon
 hydrogen bonds, wherein the hydrogen atoms (having both hydrogen nucleii
 and electrons) are transferred from the catalyst to a carbon atom.
 The hydrogen donor for hydrogenation reactions need not comprise H.sub.2.
 In fact, it is known in the art that carbon-carbon double bonds, and
 carbon-oxygen double bonds can be reduced via "transfer hydrogenation"
 reactions. Transfer hydrogenations do not employ H.sub.2 as a hydrogen
 donor. A variety of hydrogen donors for transfer hydrogenation reactions
 are known, which include but are not limited to hydrazine, alcohols, and
 silanes.
 The most preferred hydrogen donor is H.sub.2, i.e. hydrogen gas. The
 H.sub.2 can be present at a pressure from about atmospheric pressure to
 about 3000 psig. Preferably, H.sub.2 is present at a pressure from 100
 psig to about 1000 psig. Most preferably, H.sub.2 is present at a pressure
 from about 400 psig to about 750 psig.
 In the instant invention, the reduction of a 4-chromanone trienol material
 occurs in the presence of at least one catalyst. Catalysts are compounds
 or compositions which accelerate or improve the rate or selectivity of
 chemical reactions without substantial consumption of the catalyst
 compound or composition.
 In one group of embodiments, the catalyst comprises Raney nickel, Raney
 cobalt, copper chromite, or a mixture thereof. In a particularly preferred
 embodiment, the catalyst comprises Raney nickel. As is well known in the
 art, each of these types of catalysts may or may not contain small
 quantities of modifier or promoter materials, such as another transition
 metal, sulfur or halide compounds. Raney nickel catalysts are particularly
 preferred catalysts for hydrogenation reactions employing H.sub.2 as a
 hydrogen donor.
 In alternative embodiments, the catalyst of the process comprises at least
 one transition metal, transition metal salt, transition metal complex, or
 a mixture thereof In these embodiments, the transition metal, transition
 metal salt, or transition metal complex may comprise chromium, molybdenum,
 tungsten, manganese, rhenium, iron, ruthenium, osmium, cobalt, rhodium,
 iridium, nickel, palladium, platinum, or copper. In preferred embodiments,
 the transition metal, transition metal salt, or transition metal complex
 may comprise nickel, palladium, platinum, ruthenium, rhodium, rhenium, or
 chromium.
 Preferred transition metal salts comprise positively charged transition
 metal ions having chlorides, fluorides, bromides, iodides, nitrates,
 phosphates, sulfates, carboxylates, acetylacetonates, hydroxides, and the
 like as negatively charged counter-ions.
 Typically, the transition metal components of the catalysts of the process
 are present in a quantity of from about 0.000001 to about 10 mole %, based
 on the moles of 4-chromanone trienol material, or more preferably from
 about 0.5 mole % to about 1.0 mole %.
 In a preferred group of embodiments, the transition metal, transition metal
 salt, or transition metal complex comprising the catalyst is dispersed on
 or bonded to at least one support material. A wide variety of support
 materials are known as suitable in the art, and include but are not
 limited to support materials comprising carbon, activated charcoal,
 silica, alumina, titania, zirconia, a zeolite, a polymer, barium sulfate,
 or calcium sulfate. When the support material is a polymer, it is
 preferably an organic polymer or resin having functional groups suitable
 for bonding to the transition metal salt or complex.
 In the embodiments comprising supported catalysts, the transition metal,
 transition metal salt, or transition metal complex comprises from about
 0.1 to about 10 weight percent, based on the weight of the support
 material.
 The instant process for reducing a 4-chromanone trienol material can be
 carried out in the absence of solvent. Alternatively the process can be
 conducted in the presence of at least one solvent, or a mixture of
 solvents. A wide variety of solvents suitable for reduction reactions are
 known in the art, and include but are not limited to water, C.sub.1
 -C.sub.12 alcohols, C.sub.2 -C.sub.20 ethers, C.sub.1 -C.sub.12 esters, or
 alkyl or aryl C.sub.5 -C.sub.25 compounds containing only carbon and
 hydrogen. Preferred solvent species include, but are not limited to
 methanol, ethanol, n-propanol, isopropanol, butanol, ethyl acetate,
 ethylene glycol and ethylene glycol ethers, propylene glycol and propylene
 glycol ethers, and the like.
 The reduction of a 4-chromanone trienol is carried out under conditions and
 for a time sufficient to form at least some of a tocopherol compound.
 Suitable conditions and reaction times can vary widely depending on the
 nature of the 4-chromanone trienol material, the type of reduction
 reaction and the quantity of the hydrogen donor, the catalyst, the reactor
 design, and a variety of other factors, as will be apparent to those of
 skill in the art.
 Reduction reactions employing highly reactive reducing agents, such as
 boranes, aluminum hydrides, or silanes may be carried out below ambient
 temperatures, including temperatures as low as -78.degree. C., or as high
 as 250.degree. C. When the reduction reaction comprises a hydrogenation,
 hydrogenation is typically conducted at a temperature from about
 50.degree. C. to about 250.degree. C. Preferably, hydrogenations are
 conducted at a temperature from about 135.degree. C. to about 200.degree.
 C.
 The process of the instant invention can be carried out in batch reactors,
 or continuous reactors. The catalyst can be dissolved in the reaction
 medium, present as a slurry in the reaction medium, present in a fluidized
 bed, or present in a fixed bed. Suitable reaction times vary widely
 depending on other parameters of the reduction reaction. Typically the
 reaction time is from about 0.5 to about 48 hours. In certain preferred
 embodiments, the reaction time is from about 1 to 10 hours.
 In one embodiment, the process of the invention additionally comprises
 removal of the protecting group from a protected tocopherol derivative, to
 form a tocopherol having the structure
 ##STR15##
 wherein R.sub.2 and R.sub.3 are hydrogen or methyl.
 In certain embodiments of the the invention, the 4-chromanone trienol
 material is obtained by condensing farnesylacetone
 ##STR16##
 with a 2-acetyl-hydroquinone compound of the formula
 ##STR17##
 wherein R.sub.2 and R.sub.3 are methyl or hydrogen, and PG is hydrogen or a
 protecting group.
 In other embodiment of the invention, the farnesylacetone is produced by a
 method comprising:
 (a) reacting farnesol with a halogenating agent to provide a farnesyl
 halide compound;
 (b) condensing the farnesyl halide compound with an acetoacetate ester, in
 the presence of a base, to provide a farnesyl acetoacetate ester; and
 (b) hydrolyzing and decarboxylating the farnesyl acetoacetate ester; so as
 to produce farnesylacetone.
 The farnesol starting material of this embodiment may be provided by
 traditional methods of organic chemistry known in the art; or the farnesol
 may be isolated from natural or microbial sources, which may be improved
 by the methods of modern biotechnology as disclosed in U.S. Provisional
 Application Ser. No. 60/091,686, entitled "Method of Vitamin Production",
 to which this application claims priority. A variety of halogenating
 agents are known in the art for converting alcohols to alkyl halides.
 PBr.sub.3 is preferred halogenating agent for converting farnesol to
 farnesyl bromide, a preferred farnesyl halide compound. Condensation of
 acetoacetate esters with alkyl halides, and hydrolysis and decarboxylation
 of the resulting substituted acetoacetate esters is well known in the art.
 Methylacetoacetate and ethylacetoacetate are preferred acetoacetate esters
 for condensation with farnesyl halides.
 In one highly preferred embodiment, the instant invention provides a
 process for preparing gamma-tocopherol by hydrogenation, comprising
 reacting
 ##STR18##
 and H.sub.2 at a pressure from about 400 to about 750 psig; in a reactor
 containing a solvent and a Raney nickel catalyst, at a temperature from
 about 135.degree. C. to about 200.degree. C., for a time from about 1 to
 about 10 hours. The starting compounds of the invention may be readily
 synthesized using alternative techniques generally known to synthetic
 organic chemists. Suitable experimental methods for making and
 derivatizing aromatic compounds are described, for example, in the
 references cited in the Background section herein above, the disclosures
 of which are hereby incorporated by reference for their general teachings
 and for their synthesis teachings. Methods for making specific and
 preferred compounds of the present invention are described in detail in
 Examples 1 and 2 below.
 Experimental
 The following examples are put forth so as to provide those of ordinary
 skill in the art with a complete disclosure and description of how the
 compounds claimed herein are made and evaluated, and are intended to be
 purely exemplary of the invention and are not intended to limit the scope
 of what the inventors regard as their invention. Efforts have been made to
 ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.)
 but some errors and deviations should be accounted for. Unless indicated
 otherwise, parts are parts by weight, temperature is in .degree. C. or is
 at room temperature, and pressure is at or near atmospheric.

EXAMPLE 1
 This example illustrates the production of d,l-gamma-tocopherol.
 A solution of 18.9 grams (0.0446 mole) of the 7,8-dimethyl-4-chromanone
 tocotrienol 8, in 200 ml of ethyl alcohol was mixed with 2 grams
 (ethanol-wet weight) of Raney nickel catalyst, and hydrogenated with
 agitation at 500 psi of H.sub.2 and 150.degree. C. for 7 hrs. The reaction
 was cooled, vented, the catalyst filtered off, and the filtrate stripped
 of solvent under vacuum to leave 18.9 grams of a light yellow viscous oily
 product. Analysis of the product by proton NMR, mass spectroscopy, and IR
 spectroscopy established that it was gamma-tocopherol; assay by
 quantitative gas chromatography disclosed a composition of 97.07 wt
 %gamma-tocopherol, 4, the remainder being ethanol. The yield was 98.9% of
 theory.
 EXAMPLE 2
 This example is a comparative example to illustrate that the procedure for
 preparing gamma-tocopherol of Example 1 does not work for preparing
 alpha-tocopherol.
 A solution of 6.2 grams of 4-chromanone 6 in 200 ml of ethanol was mixed
 with 2 grams (wet wt.) of Raney nickel catalyst and hydrogenated at
 150.degree. C., 500 psig H.sub.2, with agitation for 7 hours. Workup as
 described in Example 1 gave 6.1 grams of a yellow syrup which was shown by
 proton NMR analysis to have no peaks consistent with the presence of
 olefins. Proton resonances observed (quartet, j=12 hz, 2.66 ppm) were
 consistent with a methylene at position 3, alpha to carbonyl; IR analysis
 showed the presence of the carbonyl group (1663 cm.sup.-1) and the mass
 spectrum showed m/e 444 (calc. for 11, 444). Gas chromatographic analysis
 did not detect the presence of any alpha-tocopherol in the crude product.
 Throughout this application, various publications are referenced. The
 disclosures of these publications in their entireties are hereby
 incorporated by reference into this application in order to more fully
 describe the state of the art to which this invention pertains.
 It will be apparent to those skilled in the art that various modifications
 and variations can be made in the present invention without departing from
 the scope or spirit of the invention. Other embodiments of the invention
 will be apparent to those skilled in the art from consideration of the
 specification and practice of the invention disclosed herein. It is
 intended that the specification and examples be considered as exemplary
 only, with a true scope and spirit of the invention being indicated by the
 following claims.