Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
  • C07F9/02—Phosphorus compounds
  • C07F9/28—Phosphorus compounds with one or more P—C bonds
  • C07F9/54—Quaternary phosphonium compounds
  • C07F9/5428—Acyclic unsaturated phosphonium compounds
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
  • C07F9/02—Phosphorus compounds
  • C07F9/28—Phosphorus compounds with one or more P—C bonds
  • C07F9/54—Quaternary phosphonium compounds
  • C07F9/5442—Aromatic phosphonium compounds (P-C aromatic linkage)

Definitions

• the present invention relates to a process for the preparation of quaternary phosphonium salts by reacting a tertiary phosphine with an optionally substituted, saturated or mono- or polyunsaturated electrophile with 3 to 25 carbon atoms in ternary solvent mixtures.
• Quaternary phosphonium salts serve as starting materials or intermediates in the synthesis of mono- or polyunsaturated organic valuable substances or active substances by means of the Wittig reaction.
• target compounds include terpenes, in particular carotenoids such as e.g. /? - Carotene or retinoids such as Vitamin A acetate. These are still produced using the Wittig reaction on a total synthetic scale on an industrial scale.
• DE-A 27 27 384 discloses a process for the preparation of aqueous polyenyltriarylphosphonium salt solutions which i.a. characterized in that organic solvents used in the production are driven off with steam from the crude product solution.
• DE-A 27 29 974 also describes a process for the preparation of aqueous, finely divided dispersions of polyenyltriarylphosphonium salts in a corresponding manner.
• EP-A 0 579 113 relates to a process for the preparation of cyclic acetals of 3-formyl-2-butenyl-triphenylphosphonium chloride.
• the substep of the reaction of the chloride with triphenylphosphine is carried out in an alkanol with 1 to 3 carbon atoms and / or an aliphatic or cycloaliphatic hydrocarbon with 6 to 8 carbon atoms or a corresponding hydrocarbon mixture.
• DE-A 25 05869 discloses a process for the preparation of symmetrical carotenoids from the molecular halves by dimerizing their phosphonium salts in two-phase reaction systems.
• the object of the present invention was to find conditions for the production of organic phosphonium salts under which an undesired precipitation of the phosphonium salts and the disadvantages of the previously known processes are avoided.
• the object was surprisingly achieved according to the invention by providing a process for the preparation of quaternary phosphonium salts by reacting a trialkyl, trialkenyl or triarylphosphine with an optionally substituted, mono- or polyunsaturated aliphatic, cycloaliphatic or aromatic-aliphatic alcohol with 3 to 25 Carbon atoms or its carboxylic acid esters or ethers in the presence of an acid or an optionally substituted, aliphatic, cycloaliphatic or aromatic-aliphatic halide having 3 to 25 carbon atoms, which is characterized in that the reaction is carried out in a ternary solvent mixture.
• the process according to the invention is suitable for the preparation of quaternary phosphonium salts starting from aliphatic, cycloaliphatic or aromatic-aliphatic alcohols with 3 to 25 carbon atoms which may in each case be unsaturated one or more times olefinically or acetylenically, and still further substituents or functional groups which are stable under the reaction conditions can wear. It is also suitable for the preparation of quaternary phosphonium salts starting from the corresponding carboxylic acid esters of these alcohols, preferably those derived from saturated aliphatic carboxylic acids.
• the process is also suitable for the preparation of quaternary phosphonium salts starting from aliphatic, cycloaliphatic or aromatic-aliphatic halides with 3 to 25 carbon atoms, which can be saturated or also mono- or polysolefinically or acetylenically unsaturated and, in addition, also others can carry stable substituents or functional groups under the reaction conditions.
• suitable starting materials for the process according to the invention are, in addition to the alcohols mentioned, the ethers derived therefrom, the newly added ether residue being able to contain 1 to 6 carbon atoms and usually an aliphatic, sometimes also a cyclic or aromatic and optionally substituted Represents rest.
• the starting compounds to be reacted according to the invention with a tertiary phosphine can be branched or unbranched and contain cyclic structural elements, which in turn can be saturated, unsaturated or aromatic, the mono- individual structural elements, in turn, substituents such as halogen atoms, alkyl radicals having one to 7 carbon atoms such as methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, pentyl and / or hexyl, or else Heteroatoms such as N, O, which in turn can carry further substituents.
• Halogen is to be understood as F, Cl or Br in the context of the entire present invention.
• substituents include, for example, amines such as NH 2) dibenzylamine and dimethylamine, but also oxygen-bonded substituents such as methoxy-, acety- or benzyloxy-.
• the starting compounds can also under the reaction conditions stable functional groups such.
• All mono- or poly-olefinically unsaturated compounds mentioned in the context of the present invention can be present or used or obtained in the form of their respective double bond isomers or in the form of mixtures thereof.
• the starting compounds are reacted with a tertiary phosphine.
• the structure of the organic residues of the phosphine is not critical and can be varied over a wide range.
• the organic radicals of the phosphine can be selected from the groups of the alkyl, alkenyl or aryl radicals having 1 to 9 carbon atoms and, within these groups, the same or different, preferably the same.
• the radicals mentioned may in turn be substituted, for example by one or more halogen atoms or else one or more alkyl radicals having 1 to 4 carbon atoms, such as e.g. Methyl, ethyl, isopropyl and / or part.
• Suitable phosphines include Trimethyl, triethyl and triallyphosphine as well as triphenyl, tri-para-tolyl, tri-ortho-tolyl and trimesityl phosphine.
• a particularly preferred tertiary phosphine is triphenylphosphine.
• a ternary solvent mixture is to be understood as a mixture of substances which contains three different solvent components and preferably consists of three different solvent components.
• the individual components are preferably distinguished by a different polarity or different release properties. They can be completely or partially miscible with one another and form a mixture which can be single or, in the case of partially miscible components, two or more phases.
• the implementation to be carried out in the context of the method according to the invention can take place independently of one another in one or more of the present phases.
• Suitable solvent components are: water, alcohols with 1 to 6 carbon atoms and 1, 2 and / or 3 hydroxyl functions such as e.g. Methanol, ethanol, propanol, isopropanol, 1-butanol, 2-butanol, glycol, 1,2-propanediol, 1,3-propanediol or mixtures thereof and hydrocarbons with 5 to 12 carbon atoms or mixtures thereof.
• Suitable hydrocarbons can be branched or unbranched aliphatic, cyclic, cycloaliphatic, aromatic and aromatic-aliphatic.
• Examples include: n-pentane, n-hexane, cyclohexane, methylcyclohexane, 1, 2-dimethylcyclohexane, 1,3-dimethylcyclohexane, 1,4-dimethylcyclohexane, ethylcyclohexane, 2-methylhexane. 3-methylhexane, n-heptane, cycloheptane, methylcycloheptane, n-octane, benzene, toluene, ortho-xylene, meta-xylene, para-xylene or mixtures thereof.
• water it has proven to be advantageous to use water as one of the solvent components. Furthermore, it has proven to be advantageous to use, in addition to water as the first component, an alcohol such as methanol or ethanol as the second component and a hydrocarbon as the third component. It is not necessary to use the individual components in pure form. Thus, it can sometimes be advantageous to use a mixture of different hydrocarbons as the hydrocarbon component, for example a mixture of different isomers of heptane or also hydrocarbon cuts consisting of hydrocarbons having 6 to 8, preferably 6 or 7, particularly preferably 7, carbon atoms.
• Typical ingredients of such a C 7 cut which can also be referred to as technical heptane or in the context of the present invention as heptane, usually comprise at least one of the following compounds: hexane, heptane, octane, isooctane, cyclohexane, toluene, cyclopentane, methylcyclopentane, dimethylcyclopentane ( 1,1-, 1,2-, 1,3-), ethylcyclopentane, 2-methylhexane, 3-methylhexane, 2-methylheptane, 3-methyl ylheptane, 4-methylheptane, 2-ethylhexane, 3-ethylhexane, methylcyclohexane, dimethylcyclopentane (1,1-, 1, 2-, 1,3-) and the like.
• the selected hydrocarbon component can also contain aromatic and / or aliphatic-aromatic mass components, provided that
• Comparable considerations can also be made for the other components of the solvent mixture to be used according to the invention.
• an alcohol such as methanol, ethanol or n- or iso-propanol can be chosen as the alcohol component, which contains further alcohols as secondary constituents or impurities.
• the alcohol component selected can also Contain water, which is then attributed to the water component of the tertiary solvent mixture according to the invention.
• the usual low water content of technical solvents should not be considered as an independent third component of the solvent mixture.
• An example of an alcohol containing water is methanol, which can contain up to about 40% by weight of water. Such methanol is to be regarded as a preferred solvent for the alcohol component of the ternary solvent mixtures to be used according to the invention.
• the total amount of the finished ternary solvent mixture is at least about 5% by weight, preferably at least about 10% by weight, of water.
• Solvent mixtures preferred in the context of the present invention accordingly consist of water, methanol and heptane, methanol being able to be used in a non-predried form, heptane being an isomer mixture as described above and at least about 5% by weight, preferably at least about 10, of the finished solvent mixture % By weight consists of water.
• the proportions of the alcohol or hydrocarbon component can in principle be freely selected within wide limits. It has proven to be expedient to use the alcohol component as the main component in quantitative terms. It is advantageous to use those solvent mixtures which consist of at least about 50% by weight of the alcohol component, preferably methanol, and additionally contain at least about 10% by weight of water. Ternary solvent mixtures which are particularly preferred in the process according to the invention consist of approximately 55-85% by weight of methanol, 10-25% by weight of heptane and 5-20% by weight of water,
• the ternary solvent mixtures which can be used in the process according to the invention can form one, two and, if appropriate, also multiphase mixtures. Mixtures which are in the form of two-phase mixtures, generally in the form of an aqueous and an organic phase, are preferably used.
• the process according to the invention is particularly suitable for the preparation of quaternary phosphonium salts of the general formula I.
• R 1 is an optionally substituted, mono- or polyunsaturated aliphatic, cycloaliphatic or aromatic-aliphatic radical with 3 to 25 carbon atoms
• R 2 is an alkyl, alkenyl or aryl radical with 1 to 9 carbon atoms
• X is the anion equivalent of an organic or inorganic Acid means by reacting a phosphine of the general formula II
• R 1 has the meaning given above and R 1 'is an optionally substituted, aliphatic, cycloaliphatic or aromatic-aliphatic radical having 1 to 21 carbon atoms, Y OH, Cl, Br, O (CO ) R 3 or OR 3 and R 3 is an aliphatic hydrocarbon radical having 1 to 6 carbon atoms and R 4 is H or CH 3 and in the case of the reaction of an electrophile of the general formula IV R 1 in formula I for a structural element of the general Formula V
• R 4 R 1 ' ⁇ c (V) stands, wherein R1 'and R 4 have the meaning given above.
• phosphines include: trimethyl, triethyl and triallyphosphine and triphenyl, tri-para-tolyl, tri-ortho-tolyl and trimesitylphosphine.
• Preferred leaving groups Y of the general formulas III and IV are: OH, Cl, Br, OR 3 or O (CO) R 3 , ie an ester derived from an acid R 3 COOH and an alcohol, where R 3 is an aliphatic hydrocarbon radical Represents 1 to 6 carbon atoms.
• the esters derived from acetic acid are particularly preferred.
• the process according to the invention is suitable for the preparation of quaternary phosphonium salts of the general formula I '
• R 1 ' has the meaning given above
• R 2' is an aryl radical having 1 to 9 carbon atoms R 4 'H or CH 3
• X is the anion equivalent of an organic or inorganic acid, by reacting a phosphine of the general formula II' P (R 2 ' ) 3 (II'), where R 2 'has the meaning given above, with an optionally substituted, mono- or polyunsaturated electrophile of the general formulas IV or VI,
• electrophiles which can be used according to the invention are the following compounds, the alcohols mentioned also being able to be used in the form of their chlorides or bromides and, where appropriate, hydroxyl and / or carbonyl functions present in protected form, for example as acetals, ketals and / or ethers may be present: retinol, retinol acetate (Viatmin A acetate), ß-vinyl-ionol, 3,7,11-trimethyl-dodeca-1, 4,6,10-tetraen-3-ol, 1,1-dimethoxy -2-methyl-but-3-en-2-ol, 6-hydroxy-3- (7-hydroxy-3,7-dimethyl-nona-1, 3,5,8-tetraenyl) -2,4,4 -trimethyl-cyclohex-2-enone, 4- (7-hydroxy-3,7-dimethyl-nona-1, 3,5,8-tetraenyl) -3,5,5-trimethyl-
• Preferred electrophiles are, for example: retinol, retinol acetate (Viatmin A acetate),. ß-vinyl-ionol, 3,7,11-trimethyl-dodeca-1,4,6,10-tetraen-3-ol, 1,4-dibromobut-2-ene, 1,4-dichloro-but- 2-en, 4-bromo-2-methyl-but-2-enal, 4-chloro-2-methyl-but-2-enal, 4-acetoxy-2-methyl-but-2-enal, 2-bromo 2-methyl-but-3-enoic acid ethyl ester, 2-chloro-2-methyl-but-3-enoic acid ethyl ester, 6-hydroxy-3- (5-hydroxy-3-methyl-pent-3-en-1-ynyl) - 2,4,4-trimethyl-cydohex-2-enone, 6-acetoxy-3- (5-hydroxy-3-methyl-pent-3-en-1-yn
• Examples of phosphonium salts of the general formula I accessible by the process according to the invention include those which can serve as starting materials or intermediates for the synthesis of compounds of the carotenoid or retinoid series by Wittig olefination: Examples include: ⁇ -ionylidene ethyl -triphenylphosphonium hydrogen sulfate or chloride, axerphtylphosphonium hydrogen sulfate or chloride, 3,7,11,15-tetramethyl-hexadeca-2,4,6,8,10,14-hexaen-yl-1-triphenylphosphonium hydrogen sulfate or chloride , 5- (2 ', 6', 6'-trimethyl-cyclohexen-1'-yI-1 ') - 3-methyl-pentadien-2,4-yl-1-triphenylphosphonium hydrogen sulfate or chloride, 9- [2 ', 6', 6'-Trimethylcyclohexen
• the reaction of alcohols, ethers and esters according to the invention with the selected tertiary phosphine is advantageously carried out in the presence of an organic or inorganic acid.
• Suitable acids include hydrochloric acid, sulfuric acid, hydrobromic acid, formic acid, acetic acid, propionic acid or phosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid, para-toluenesulfonic acid, benzenesulfonic acid or trifluoroacetic acid, preferably hydrochloric acid and sulfuric acid. These are usually used in an amount of about 0.9 to about 1.1 equivalents, based on the amount of phosphine used.
• the anion equivalents of said acids, in particular hydrochloric, sulfuric and hydrobromic acids usually form the counterions X of those in the context of Phosphonium salts of the general formula I prepared according to the process of the invention
• the substituted halide ion in particular Cl or Br, usually forms the counterion X of said phosphonium salts of the general formula I.
• a very particularly preferred embodiment of the process according to the invention is characterized in that for the preparation of quaternary phosphonium salts of the formula I "
• reaction conditions under which the process according to the invention is usually carried out have no particular requirements.
• the reaction temperature, concentrations of the starting materials in the selected solvent mixture, reaction times and purity of the reagents used are generally in areas which are well known to the person skilled in the art and for example in Houben-Weyl, "Methods of Organic Chemistry", Volume 12 / 1, Thieme, Stuttgart, 1963 and Volume E1, Thieme, Stuttgart, 1982 or also in Johnson, Kaska, Starzewski, Pixon "Ylides ans Imines of Phosporus", Wiley, New York, 1993.
• the electrophile to be reacted is usually used in a purity of about 50 to about 99%.
• the selected phosphine is generally used in a purity of about 80 to about 99.5% and in an approximately equimolar ratio to the electrophile, ie in about 0.9 to about 1.1 equivalents based on the amount of electrophile.
• the reaction is advantageously carried out in the presence of an organic or inorganic acid.
• Hydrochloric acid is preferably used, usually in the form of an approximately 10 to approximately 36% by weight aqueous solution or sulfuric acid in the form of an approximately 70 to approximately 98% by weight aqueous solution.
• aqueous sulfuric acid especially those with a concentration of about 70 to about 80% by weight.
• the selected acid is usually used in an amount, based on the amount of electrophile to be reacted, of from about 0.9 to about 1.2 equivalents.
• the reaction procedure does not differ fundamentally from the procedures in the processes known per se to the person skilled in the art. This is usually done
• Phosphine in the chosen ternary solvent mixture and then, in the case of the reaction of alcohols or esters as electrophile, the acid.
• the acid is usually added slowly, possibly dropwise and at temperatures from about room temperature to about 70 ° C.
• the acid addition is then usually complete after about 1 to about 10 hours.
• the electrophile to be reacted can be added at the same time or with a time delay, usually after the acid has been added, and is normally carried out within the same temperature range and is normally also completed after 1 to 10 h. To complete the conversion, the reaction mixture is usually stirred at temperatures in the specified range.
• reaction vessel There are no special requirements for the reaction vessel or the reactor.
• the reaction mixture can be worked up and the reaction product can be isolated by methods known per se to the person skilled in the art.
• ternary solvent mixture used according to the invention it is particularly advantageous to separate the ternary solvent mixture used according to the invention from the remaining constituents of the reaction mixture after the reaction has ended and to return it to the reaction process. It may be necessary to restore the original composition of the ternary solvent mixture. This is expediently carried out by adding one or two components of the selected solvent mixture. Of course, any other composition different from the originally selected composition can also be set in this way.
• the desired process usually gives the desired phosphonium salts in excellent yields and high purity, which is a particular advantage especially for reactions on an industrial scale. In principle, however, the process can be carried out with good success on any scale.
• a further particular advantage of the method according to the invention is that the suitable composition of the ternary solvent mixture can generally largely prevent the undesired precipitation or crystallization of the phosphonium salts to be synthesized.
• the process described is particularly suitable for continuously carried out reactions on an industrial scale.
• the process according to the invention is particularly suitable for the production of quaternary phosphonium salts, which are valuable starting materials or intermediates for the production of polyisoprenoids or carotenoids and retinoids.
• the invention accordingly also relates to the use of phosphonium salts prepared by the process according to the invention for the production of polyisoprenoids, in particular retinol (vitamin A), vitamin A acetate, vitamin A propionate, vitamin A palmitate, retinal, retinoic acids,? -Carotene, ⁇ -carotene, ⁇ -carotene "Zeaxanthin, Astaxanthin, Canthaxanthin, Lycopin, Citranaxanthin, j5-Apo-8'-carotinal, Crocetin, ⁇ -Cryptoxanthin, /?
• triphenylphosphine 139.7 g of triphenylphosphine were placed in a solvent mixture consisting of 206.8 g of methanol, 44.46 g of water and 40.68 g of heptane at 40 ° C. with stirring. 72.7 g of 75% sulfuric acid were added dropwise within 1 h. Then 130 g of jff-vinyl-ionol with a purity of 92.1% were metered in over the course of 2 h, the temperature was raised to 50 ° C. and the mixture was stirred for 4 h. After extractive work-up,? -Lonolydentriphenylphosphonium hydrogen sulfate was obtained in a yield of 99.9% (based on the triphenylphosphine used).
• triphenylphosphine 585.5 g of triphenylphosphine were introduced with stirring in a mixture of 1014.2 g of methanol and 221.4 g of water at a temperature of 40 ° C. Then 304.7 g of a 75% strength sulfuric acid were added dropwise within 1 h and then 544.8 g of 92.1% strength? -Vinyl-ionol were added at a temperature of 50 ° C. in the course of 4 hours. The mixture was stirred for 4 h at 50 ° C and worked up extractively. The target compound was obtained in a yield of 97.9% of theory. Th. (Based on triphenylphosphine used).

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Biochemistry (AREA)
• General Health & Medical Sciences (AREA)
• Molecular Biology (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Priority Applications (7)

Applications Claiming Priority (2)

Publications (1)

Family

ID=34683507

Family Applications (1)

Country Status (8)

Cited By (1)

Families Citing this family (12)

Citations (3)

Family Cites Families (5)

• 2003
  • 2003-12-17 DE DE10359434A patent/DE10359434A1/de not_active Withdrawn
• 2004
  • 2004-12-14 CA CA002546480A patent/CA2546480A1/en not_active Abandoned
  • 2004-12-14 CN CN2004800375929A patent/CN1894265B/zh not_active Expired - Lifetime
  • 2004-12-14 WO PCT/EP2004/014207 patent/WO2005058924A1/de not_active Ceased
  • 2004-12-14 US US10/582,912 patent/US7547807B2/en not_active Expired - Lifetime
  • 2004-12-14 EP EP04820433A patent/EP1697388B1/de not_active Expired - Lifetime
  • 2004-12-14 DE DE502004011432T patent/DE502004011432D1/de not_active Expired - Lifetime
  • 2004-12-14 JP JP2006544306A patent/JP4659757B2/ja not_active Expired - Lifetime
  • 2004-12-14 AT AT04820433T patent/ATE474844T1/de not_active IP Right Cessation

Patent Citations (3)

Also Published As

Similar Documents

Legal Events