WO2006042835A1 - Procede de preparation d'alcools primaires aliphatiques et intermediaires associes pour la mise en oeuvre de ce procede - Google Patents

Procede de preparation d'alcools primaires aliphatiques et intermediaires associes pour la mise en oeuvre de ce procede Download PDF

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WO2006042835A1
WO2006042835A1 PCT/EP2005/055296 EP2005055296W WO2006042835A1 WO 2006042835 A1 WO2006042835 A1 WO 2006042835A1 EP 2005055296 W EP2005055296 W EP 2005055296W WO 2006042835 A1 WO2006042835 A1 WO 2006042835A1
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group
atoms
straight
process according
alkyl
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Georgios Sarakinos
Quirinus Bernardus Broxterman
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Dsm Ip Assets B.V.
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    • 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
    • C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
    • C07F3/02—Magnesium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/32—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions without formation of -OH groups

Definitions

  • High-molecular-weight aliphatic saturated primary alcohols for instance with 24- 32 C-atoms, preferably with 26-30 C-atoms, are useful products for use for instance in food or pharmaceutical products.
  • policosanol is a mixture of high- molecular-weight aliphatic primary alcohols with as its main component octacosanol (C28). It is used for instance for improvement of serum lipid profiles, which makes it an interesting compound for the prevention and treatment of cardiovascular diseases, and as a cholesterol-lowering additive in foods.
  • the present invention now makes it possible to prepare high-molecular-weight aliphatic linear, straight-chain primary alcohols in a simpler synthetic process.
  • specific mixtures of high molecular-weight aliphatic linear straight-chain primary alcohols can easily be prepared e.g. by the choice of the starting materials.
  • the present invention discloses a method to prepare high-molecular-weight aliphatic linear, straight-chain primary alcohols having between 24 up to and including 32 carbon atoms, preferably between 26 up to and including 30 carbon atoms, comprising the steps of: a. transforming the alcohol group of an ⁇ -functionalised- ⁇ -hydroxy linear straight chain alkyl or alkene (i) into an alkoxy-metal complex (ii), b. optionally, followed by a transformation of the ⁇ -group into a nucleophilic group, c. followed by a coupling reaction of the component as formed on its ex ⁇ position.
  • Y is a leaving group (LG), including all halogens, or an aldehyde group
  • A is a alkylene or alkenylene group having from 3 up to and including 28 C-atoms, preferably up to and including 26 carbon atoms.
  • the component (ii) can be formed by adding a suitable reagent (acting as a base) to (i) which results in the formation of an alkoxy-metal complex.
  • a suitable reagent is for example, a metal hydride such as LiH, NaH, KH, CaH 2 , AIH 3 etc or an alkyllithium such as methyllithium, ethyllithium, etc or an alkylmagnesium halide, such as methylmagnesium chloride or bromide, ethylmagnesium chloride or bromide, etc or a trialkylaluminum such as trimethylaluminum, etc.
  • the resulting complex can be either
  • Z Li + , Na + , K + , etc or [MgCI] + , [MgBr] + , [ZnBr] + , etc or [AIMe 2 J + , [AIMeCI] + , [TiCI 2 J + , etc or [TiCI 3 J + , [SnCI 3 ] + ;
  • Z Mg 2+ , Ca 2+ , Zn 2+ , etc or [AIMe] 2+ , [AICI] 2+ , [TiCI] 2+ , etc or [TiCI 2 ] 2 ", [SnCI 2 ] 2+ etc;
  • the present invention also relates to any new component (ii).
  • a of formula (2) is an alkenylene group having from 3 up to and including 28 C-atoms
  • the complex is not known in the prior art.
  • such complex can be useful as intermediate in the preparation of high-molecular-weight aliphatic saturated primary alcohols as in the method according to the invention.
  • a of formula (2) is an alkylene group having from 13 up to and including 28 C-atoms
  • the complex is not known in the prior art either.
  • such complex can be useful as intermediate in the preparation of high molecular-weight aliphatic saturated primary alcohols as in the method according to the invention.
  • the coupling reaction is a so-called organometallic cross- coupling reaction.
  • Y is a leaving group (LG). Any leaving group known to the person skilled in the art can be used. Preferably acetate is excluded as leaving group. Examples of suitable leaving groups are for example described in D. S. Kemp & F. Vellaccio, Organic Chemistry, Worth: New York, 1980; pp 99-102, 143-144, 179-180, OSO 2 Ar (Ar represents an aryl group), OMs (OMs represents a mesylate group), OTf (OTf represents a triflate group), OP(O)(OR 11 ) 2 (R 11 is an alkyl group, preferably an alkyl group with 1 -5 C-atoms) or halogens, such as for example F, Cl, Br, I.
  • LG leaving group
  • ⁇ -halo- ⁇ -hydroxy alkylenes or alkenylenes (i) comprising a leaving group can be synthesized easily by a person skilled in the art, using known methods.
  • the starting materials for this transformation are for example ⁇ , ⁇ -dihydroxy alkylenes or alkenylenes. It was found that an organometallic cross-coupling reaction gives a high yield. Surprisingly, the complex-formation does not interfere with the catalyst as used in the organometallic cross coupling.
  • the alcohol group of an ⁇ -functionalised- ⁇ -hydroxy linear straight chain alkyl or alkene (i) is transformed into an alkoxy-metal complex (ii), whereafter an organometallic cross-coupling takes place with an organometallic reagent (R-CH 2 - M 1 (X)).
  • R-CH 2 -M 1 (X) R represents H or a linear straight-chain alkyl or alkenyl-CH 2 - group with 1 - 25 C-atoms
  • M 1 represents Li, Na, Mg, K or a boron-, zinc- or manganese based group.
  • X can be optionally present and represents a halogen group, for example I, Br, Cl or F.
  • the organometallic reagent is typically an organomagnesium (Grignard), organolithium or organozinc reagent, such as for example CH3(CH 2 ) 17 MgCI. Many such reagents are commercially available. If they are not, they can be synthesized from the corresponding inexpensive alkyl chloride, bromide or iodide by methods known to persons skilled in the art.
  • the reaction preferably is carried out in the presence of a transition metal catalyst (cat. M), which may be in the form of a neutral or cationic metal complex M 2 L 1 a L 2 b X, an anionic complex Q d [M 2 L 1 a L 2 b Xc]e, a soluble transition metal nanocluster, or as heterogeneous catalyst wherein the metal in the zero oxidation state is deposited in the form of microcrystalline material on a solid carrier, wherein M 2 can be any transition metal known to catalyze such coupling reactions, for instance Mn, Fe, Cu, Ni or Pd.
  • a transition metal catalyst cat. M
  • M transition metal catalyst
  • L 1 and L 2 are ligands (for instance optionally substituted phosphines and bisphosphines such as triphenylphosphine, bis-diphenylphosphinopropane, 1 ,1 '-diphosphaferrocene (dppf), phosphites or bisphosphites, PN ligands in which there is both a coordinating P atom and a N atom present, N-N ligands such as phenanthrolines),
  • X is an anion which may be a halide, a carboxylate or a composite anion such as BF 4 " or PF 6 "
  • Q is a cation for instance an alkaline metal ion (for instance sodium, potassium) or a tetraalkylammonium salt
  • a, b, c, d and e are integers from 0-5.
  • the clusters contain from 2 to many thousands of metal atoms and may carry ligands or anions on the outer rim.
  • suitable catalysts are Cu 2+ salts, such as Li 2 CuCI 4 .
  • Suitable carrier materials for heterogenous catalysts are, for instance, carbon black, silica, aluminum oxide.
  • M 1 represents an alkali metal, e.g. Li, Na or K, a transition metal catalyst is not particularly preferred.
  • the reaction preferably is performed under an inert atmosphere (e.g. dry nitrogen or dry argon).
  • the reaction is carried out in the presence of a solvent.
  • Suitable solvents are for instance ethyl ether, tetrahydrofuran (THF), /-propyl ether di-n-propyl ether, dimethoxyethane (DME) or methyl f-butyl ether or mixtures of these solvents with a dipolar aprotic solvent such as NMP, DMF or DMA (dimethylacetamide) in any proportion, most preferably THF, and the concentration of each of the reactants is preferably between 0.2 and 3 molar.
  • a proton source e.g. aqueous NH 4 CI
  • All steps as described above can take place in one pot; no intermediate purification steps need to take place in order to give a high yield.
  • R 1 -OH is obtained directly, wherein R 1 represents a linear, straight-chain alkyl group having 24-32, or preferably 26-30, C-atoms, which can then be isolated in a simple work-up procedure as described later in this document.
  • the product obtained from the coupling step is R 2 -OH and additionally a reduction of the double bond(s) must be performed in a separate step, to lead to the desired product R 1 -OH.
  • This hydrogenation step usually takes place in a separate pot.
  • an alkyl magnesium halide most preferably an alkyl magnesium chloride or bromide (for instance an amount of 1 to 5 equivalents, preferably 1 -2 equivalents) is reacted with 1 equivalent of an ⁇ -Y- ⁇ -alkoxy-metal complex (pre-formed in situ from the corresponding alcohol and a suitable organometallic reagent, as described above) wherein Y is a leaving group (as described above), preferably an alkyl chloride or bromide, in the presence of a transition metal catalyst.
  • the transition metal catalyst is based on a transition metal M 2 chosen preferably from Mn, Fe, Cu, Ni, Pd, most preferably Cu.
  • Suitable sources of catalyst precursors are for instance precursors of Cu 1 (for example CuCI, CuI, CuOTf), Cu" (for example CuCI 2 , Li 2 CuCI 4 ), Ni 0 (for example Ni(COD) 2 ), Ni" (for example NiCI 2 , Ni(acac) 2 , NiBr 2 ), or Pd" (for example PdCI 2 , Pd(OAc) 2 , Pd 2 (dba) 3 ), Mn 1 " (for example MnCI 3 , Mn(acac) 3 ) or Fe 1 " (for example Fe(acac) 3 ).
  • Cu 1 for example CuCI, CuI, CuOTf
  • Cu for example CuCI 2 , Li 2 CuCI 4
  • Ni 0 for example Ni(COD) 2
  • Ni for example NiCI 2 , Ni(acac) 2 , NiBr 2
  • Pd for example PdCI 2 , Pd(OAc) 2 , Pd 2 (dba) 3
  • Preformed catalysts can also be used, for example (PPh 3 ) 2 NiCI 2 , (dppp)NiCI 2 or (dppf)NiCI 2 .
  • the readily available catalyst Li 2 CuCI 4 as a solution in THF is used.
  • the amount of catalyst that is used is calculated with respect to the electrophile and is preferably lower than 0.05 equivalents, more preferably between 0.001 and 0.03 equivalents calculated with respect to the electrophile. Preferably less than 4 equivalents of each ligand with respect to the amount of metal M 2 are used.
  • the reaction is run in the presence of a 1 ,3-diene, for example 1 ,3-butadiene, isoprene or 2,3-dimethyl-1 ,3-butadiene, in a relative amount of 0.1 to 2.0 equivalents calculated with respect to the electrophile.
  • a 1 ,3-diene for example 1 ,3-butadiene, isoprene or 2,3-dimethyl-1 ,3-butadiene
  • the temperature at which the reaction is performed preferably lies between -78 to 80 0 C, more preferably between -20 and 80 0 C.
  • the reaction time required is preferably between 1 and 24 hours.
  • an alkylzinc iodide (preferred amount 1.05-1.5 equivalents calculated with respect to the electrophile) is reacted with 1 equivalent of an alkyl bromide or iodide (ii), preferably iodide, optionally in the presence of a tetraalkylammonium halide R 3 4 NX, wherein each R 3 , independently, represents an alkyl group, for instance an alkyl group with 1 -16 C-atoms and X represents a halogen, for instance Cl, Br or I, for instance n- Pr 4 NI, H-Bu 4 NBr, D-Bu 4 NI (preferred amount 1 -5 equivalents with respect to the alkyl halide), and optionally in the presence of a styrene
  • the reaction preferably is carried out in the presence of a solvent.
  • Suitable solvents that may be used are for instance ethers, NMP, DMF or mixtures thereof.
  • the reaction preferably is run at temperatures between -30 and 25 0 C.
  • the reaction time required preferably is between 2 and 30 h.
  • the nucleophilic reagent may be of the general structure RCH 2 BR 4 2 (wherein each R 4 independently represents an alkyl group, for instance an alkyl group with 1-10 C-atoms, or may be part of a ring, for instance as in 9- BBN), RCH 2 B(OH) 2 or RCH 2 B(OR 4 ) 2 , wherein R is as above.
  • alkyl-(9-BBN) reagent (preferred amount 1 -3 equivalents, calculated with respect to the amount of electrophile), is reacted with for instance an alkyl chloride, bromide or tosylate (ii), preferably a bromide or a tosylate.
  • the reaction is catalyzed by a source of Pd 0 or Pd", such as Pd(OAc) 2 , PdCI 2 , or Pd 2 (dba) 3 , preferably Pd(OAc) 2 , in an amount calculated with respect to the electrophile of 0.01-0.10 equivalents.
  • Addition of a stabilizing ligand for the metal may be beneficial.
  • the source of the phosphine ligand may also be the corresponding phosphonium salt (less susceptible to oxidation), such as (HP( ⁇ -Bu) 2 Me)BF 4 .
  • the relative amount of the phosphine may be 0.05-0.20 equivalents calculated with respect to the electrophile, preferably in a molar ratio 2:1 to Pd.
  • a base is added, for instance a phosphate salt such as Na 3 PO 4 H 2 O or K 3 PO 4 H 2 O; an alkali metal hydroxide, for instance NaOH, KOH, LiOH or CsOH; or a bulky alkoxide base such as LiOf-Bu, NaOf-Bu or KOf-Bu, in a proportion of 1 -4 equivalents calculated with respect to the electrophile.
  • the reaction preferably is carried out in the presence of a solvent.
  • Suitable solvents that can be used are the ethers mentioned above, also dioxane or a bulky alcohol, such as f-amyl alcohol.
  • THF is preferably used as the solvent with alkyl-(9-BBN) derivatives and f-amyl alcohol with alkyl boronic acids.
  • the addition of one or two equivalents of water with respect to the electrophile may be beneficial.
  • the reaction preferably is run at temperatures between 25 and 10O 0 C (higher temperatures are preferred for more unreactive alkyl chloride electrophiles).
  • the stoichiometries of these reactions are as above (for instance an excess organometallic reagent, preferably 1 -3 equivalents, most preferably 1 -1 .5 equivalents).
  • the preferred solvents are here the ethers mentioned above (preferably THF), but also toluene can be suitably used, especially when higher reaction temperatures are required.
  • Y is a halogen, but does not act as a leaving group as described above; instead, the halogen is transformed into a nucleophilic organometallic group. In this case a reversed-polarity set of coupling partners is needed.
  • This specific embodiment is also included in the present invention.
  • the transformation of the halogen Y into an organometal group can take place immediately after the formation of the alkoxy-metal complex.
  • a metal such as Li, Mg, Zn, etc is added to the solution of the alkoxy-metal (ii), so that the corresponding organometallic reagent (iii), e.g.
  • the ⁇ -halo- ⁇ -alkoxy-metal complex Y-CH 2 -CH 2 -A-CH 2 -O-Z (ii) (m 1 , pre ⁇ formed in situ from the corresponding alcohol (i) and a suitable base, as described above), is reacted with Mg metal to form an alkyl- ⁇ -halomagnesiumide- ⁇ -alkoxy-metal complex YMg-CH 2 -CH 2 -A-CH 2 -O-Z (iii), most preferably an alkyl magnesium chloride or bromide.
  • Compound (iii) is then reacted with RCH 2 Y 1 (R as above) in the presence of a transition metal catalyst.
  • An amount of, for instance, 1 to 5 equivalents, preferably 1 -2 equivalents of (iii) can be reacted with about 1 equivalent of RCH 2 Y 1 .
  • suitable RCH 2 Y 1 are alkyl halide, alkyl tosylate, etc.
  • the transition metal catalyst is based on a transition metal M 2 chosen preferably from Mn, Fe, Cu, Ni, Pd, most preferably Cu. They can be in the form of pre-formed complexes or made in situ from a catalyst precursor and one or more ligands.
  • an activator for instance a reducing agent, such as NaBH 4
  • Suitable sources of catalyst precursors are for instance precursors of Cu 1 (for example CuCI, CuI, CuOTf), Cu" (for example CuCI 2 , Li 2 CuCI 4 ), Ni 0 (for example Ni(COD) 2 ), Ni" (for example NiCI 2 , Ni(acac) 2 , NiBr 2 ), or Pd" (for example PdCI 2 , Pd(OAc) 2 , Pd 2 (dba) 3 ), Mn 1 " (for example MnCI 3 , Mn(acac) 3 ) or Fe 1 " (for example Fe(acac) 3 ).
  • Preformed catalysts can also be used, for example (PPh 3 ) 2 NiCI 2 , (dppp)NiCI 2 or (dppf)NiCI 2 .
  • the readily available catalyst Li 2 CuCI 4 as a solution in THF is used.
  • the amount of catalyst that is used is calculated with respect to the electrophile and is preferably lower than 0.05 equivalents, more preferably between 0.001 and 0.03 equivalents calculated with respect to the electrophile. Preferably less than 4 equivalents of each ligand with respect to the amount of metal M 2 are used.
  • the reaction is run in the presence of a 1 ,3-diene, for example 1 ,3-butadiene, isoprene or 2,3-dimethyl-1 ,3-butadiene, in a relative amount of 0.1 to 2.0 equivalents calculated with respect to the electrophile.
  • the temperature at which the reaction is performed preferably lies between -78 to 80 0 C, more preferably between -20 and 80 0 C.
  • the reaction time required is preferably between 1 and 24 hours.
  • an amount of, for instance, 1 to 5 equivalents, preferably 1-2 equivalents of (iii) is reacted with 1 equivalent of an alkyl halide, alkyl tosylate, etc RCH 2 Y 1 wherein Y 1 is a leaving group, most preferably a bromide or iodide, preferably iodide, in the presence of a transition metal catalyst, optionally in the presence of a tetraalkylammonium halide R 3 4 NX, wherein each R 3 , independently, represents an alkyl group, for instance an alkyl group with 1 -16 C-atoms and X represents a halogen, for instance Cl, Br or I, for instance /1-Pr 4 NI, H-Bu 4 NBr, H-Bu 4 NI (preferred amount 1 -5 equivalents with respect to the alkyl halide), and optionally in the presence of a styrene preferably a mono- or polyfluorinated styrene
  • the reaction preferably is carried out in the presence of a solvent.
  • Suitable solvents that may be used are for instance ethers, NMP, DMF or mixtures thereof.
  • the reaction preferably is run at temperatures between -30 and 25 0 C.
  • the reaction time required preferably is between 2 and 30 h.
  • the ⁇ -halo- ⁇ -alkoxy-metal complex Y-CH 2 -CH 2 - A-CH 2 -O-Z (ii) (m 1 , pre-formed in situ from the corresponding alcohol (i) and a suitable base, as described above), is reacted with Li, Na or K metal to form an ⁇ -Li- ⁇ - alkoxy-metal complex Li-CH 2 -CH 2 -A-CH 2 -O-Z (iii) or an ⁇ -Na- ⁇ -alkoxy-metal complex Na-CH 2 -CH 2 -A-CH 2 -O-Z (iii) or an ⁇ -K- ⁇ -alkoxy-metal complex K-CH 2 -CH 2 -A-CH 2 -O-Z (iii).
  • An amount of, for instance, 1 to 5 equivalents, preferably 1 -2 equivalents of (iii) is reacted preferably with an alkyl halide or tosylate RCH 2 Y 1 , preferably an alkyl bromide, iodide or tosylate.
  • a metal catalyst is not particularly preferred in these cases.
  • the stoichiometries of these reactions are as above (for instance an excess organometallic reagent, preferably 1 -3 equivalents, most preferably 1 -1 .5 equivalents).
  • the preferred solvents are here the ethers mentioned above (preferably THF), but also toluene can be suitably used, especially when higher reaction temperatures are required.
  • a proton source is added (e.g. aqueous NH 4 CI) to form an OH-group again.
  • the coupling reaction is a Wittig reaction as for instance generally described in M. B. Smith and J. March in March's Advanced Organic Chemistry, Reactions, Mechanisms and Structure, 5 th Edition, Wiley & Sons: New York, 2001 ; pp 1231 -1237 and in F. A. Carey and R. J. Sundberg in Advanced Organic Chemistry, Part B: Reactions and Synthesis, 3 rd Edition, Plenum: New York, 1990: pp 95-102. In that case Y is an aldehyde.
  • a suitable reagent base
  • R 7 is an alkyl having less than or equal to 6 carbon atoms or aryl, for instance phenyl group.
  • reagents that will not attack the aldehyde group
  • metal hydrides such as LiH, NaH, KH, CaH 2 , AIH 3
  • the product R 2 OH having one or more double bonds must be hydrogenated to yield the desired product alcohol R 1 -OH.
  • an alkyl triphenylphosphonium halide most preferably an alkyl triphenylphosphonium chloride, bromide or iodide is reacted with a base such as an organolithium reagent, for instance n-butyllithium, n-hexyllithium or phenyllithium, or an amide ion, for instance lithium, sodium or potassium amide or hexamethyldisilylamide, or a lithium, sodium or potassium alkoxide, preferably methoxide, ethoxide, f-butoxide or f-amylate, in a stoichiometry of, for instance, 1 to 1 .5 equivalents (preferably 1.01 -1.1 equivalent) to produce the phosphonium ylide reagent.
  • a base such as an organolithium reagent, for instance n-butyllithium, n-hexyllithium or phenyllithium, or an amide ion
  • the Wittig reaction preferably is carried out in the presence of a solvent.
  • the preferred solvents are ethers, such as ethyl ether, THF, /-propyl ether, di-n-propyl ether, dimethoxyethane (DME) or methyl f-butyl ether; or DMSO, liquid ammonia, toluene, xylenes, ethanol or other low molecular weight alcohols, water, dichloromethane or mixtures thereof, and the concentration of each of the reactants is preferably between 0.2 and 3 molar.
  • the temperature at which the above reaction is performed depends on the ease of formation of the ylide and preferably lies between -78 and +100 0 C.
  • the reaction time required is preferably between 1 and 24 hours.
  • the preformed (as above) ⁇ -alkoxymetal- ⁇ -aldehyde (ii) (preferably 1 -1 .5 equivalents) is added without isolation and purification of the phosphonium ylide.
  • the temperature at which the reaction is performed is preferably between 0 and 100 0 C, more preferably between 20 and 70 0 C.
  • the reaction time required is preferably between 1 and 24 hours, more preferably between 1 and 8 h.
  • the nucleophilic reagent is formed by treatment of a phosphonate reagent of type RCH 2 P(O)(OR 12 ) 2 with an appropriate strong base (as defined above in relation to the Wittig chemistry).
  • R, and A are defined as above.
  • R 12 represents, for instance, a small alkyl group, for instance a methyl or ethyl group. This modification of the original Wittig reaction is called Horner- Emmons, Wadsworth-Emmons or Wittig-Horner reaction.
  • the nucleophilic reagent is formed by treatment of alkoxy-metal complex (ii) with a phosphine PR 7 3 (as above) followed by addition of another equivalent of a suitable base (as above) to form phosphonium ylide (iv) (where Y is a halogen, A is a alkylene or alkenylene group having 3 up to and including 28 C-atoms and Z is as above). Without isolation, (iv) is reacted (as above) with aldehyde RCHO (R is as above) to give, after acidic quench, product R 2 -OH, which after isolation is hydrogenated to desired alcohol R 1 -OH.
  • the reverse-polarity Wittig reaction can also be modified to a Homer-Emmons alternative (via a phosphonate reagent) as described above.
  • a combination of methods can be used based on differences in for example melting point, boiling point, polarity, solubility, molecular size, functional groups and density.
  • solubility of the alcohols in water is negligible, it is possible to remove salts and other polar compounds by contacting the solution with a polar solvent like water.
  • the melting point of the produced alcohols generally is in the range 70-90 0 C, highest in a mixture free of salt, making crystallization from a concentrated solution in a solvent with a suitable polarity, or from a melt (in one or more steps) a possible purification method. Also adsorption on hydrophobic surfaces, for instance combined with chromatographic techniques is suitable. Also methods based on enhanced vapour pressure, for instance in supercritical media, are within reach. Also molecular filtration techniques based on size and polarity are possible.
  • a crystallization step is usually suitable, although solidification by evaporating the solvent from a purified solution can also be used. Crystals can be separated by filtration or sedimentation and subsequently dried.
  • stirred tanks For executing unit operations related to purification, isolation and recovery of the produced alcohols numerous (continuous / batch) equipment is available in the market: For instance stirred tanks, centrifuges, (pulsated) columns for liquid - liquid extraction, stirred tanks, columns, and dedicated cooled/heated surfaces for (melt-) crystallization, stirred tanks and columns like simulated moving beds for adsorption / chromatography, high pressure columns for supercritical extraction, membrane filtration equipment for molecular separation, centrifuges and rotating / static (pressure-)filters for solid-liquid separation and heated (stirred / moving) chambers for drying.
  • the invention will hereafter be elucidated by the following non-limiting example.

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Abstract

L'invention se rapporte à un nouveau procédé de préparation d'alcools primaires, à chaîne droite, linéaires, aliphatiques, à poids moléculaire élevé, possédant entre 24 et 32 atomes de carbone inclus, ledit procédé comprenant les étapes consistant à: (a) transformer le groupe alcool d'un alkyle ou alcène (i) à chaîne droite, linéaire, α-fonctionnalisé-φ-hydroxy en un complexe alcoxy-métal (ii), (b) à transformer éventuellement le groupe-a en un groupe nucléophile, et (c) à effectuer une réaction de couplage de ce composant tel que formé sur sa position-a. L'invention se rapporte en outre à un procédé de préparation de ces alcools protégés mettant en jeu une réaction de couplage croisé organométallique ou une réaction de Wittig, ainsi qu'à de nouveaux intermédiaires et des composés de départ pour la mise en oeuvre de ce procédé.
PCT/EP2005/055296 2004-10-18 2005-10-17 Procede de preparation d'alcools primaires aliphatiques et intermediaires associes pour la mise en oeuvre de ce procede WO2006042835A1 (fr)

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WO2011152501A1 (fr) * 2010-06-04 2011-12-08 株式会社カネカ Procédé de préparation d'alcools primaires aliphatiques, saturés, à longue chaîne

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