Process for the purification of phosphonium salts

Details Process for the purification of phosphonium salts Process for the purification of phosphonium salts

2002-06-05

2003-10-07

Vollano, Jean F. (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Phosphorus containing

C210S660000

Reexamination Certificate

active

06630605

ABSTRACT:

The present invention relates to a process for the purification of phosphonium salts which have a hydrocarbon radical with 5 to 40 carbon atoms, in particular ionylideneethylphosphonium salts such as 3,7,11-trimethyldodeca-2,4,6,10-tetraen-1-ylphosphonium salts.
To prepare carotenoids in many cases phosphonium salts and aldehydes are reacted in a Wittig reaction. Thus, to synthesize lycopene, a red pigment which occurs as natural carotenoid in tomatoes, 3,7,11-trimethyldodeca-2,4,6,10-tetraen-1-ylphosphonium salts are reacted for example with 2,7-dimethyl-2,4,6-octatrienedial. &bgr;-Ionylideneethylphosphonium salts can be converted correspondingly into &bgr;-carotene and 2-hydroxy-&bgr;-ionylideneethylphosphonium salts can be converted correspondingly into zeaxanthin etc.
EP 0 382 067 describes the preparation of 3,7,11-trimethyldodeca-2,4,6,10-tetraen-1-ylphosphonium salts by reacting 3,7,11-trimethyldodeca-1,4,6,10-tetraen-3-ol with at least one equivalent of triarylphosphine in an inert solvent in the presence of a C
1
-C
6
-alkanoic acid or boron trifluoride-etherate. The phosphonium salt which is initially produced can be converted into the chloride, bromide, sulfate, hydrogen sulfate, phosphate or a sulfonate.
No simple process for the purification of the phosphonium salts, in particular for removing the phosphine which is employed in excess, or the acid.
It is an object of the present invention to provide a process which makes it possible to purify the crude phosphonium salts simply and effectively.
We have found that this object is achieved by use of a solid phase. The use of a solid phase has the advantage over processes of purification by extraction from one liquid phase into another liquid phase that any solvent can be used without the need to ensure the formation of two phases.
In a first aspect, the invention relates to a process for the purification of phosphonium salts of the formula
R—P
⊕
R′
3
X
⊖
in which R is a hydrocarbon radical with 5 to 40 carbon atoms, R′ is C
1
-C
4
-alkyl or C
6
-C
10
-aryl and X is an equivalent of an anion, in which
a) a solution of the crude phosphonium salt is passed over a bed of a cation exchange resin in salt form,
b) the cation exchange resin is washed with at least one polar protic or aprotic and/or at least one nonpolar solvent, preferably with at least one polar protic and at least one nonpolar solvent in any sequence, and
c) the phosphonium salt is eluted from the cation exchange resin with an electrolyte solution, where appropriate in combination with a polar aprotic solvent.
In a second aspect, the invention relates to a process for the purification of phosphonium salts of the formula
R—P
⊕
R′
3
X
⊖
in which R, R′ and X have the meanings indicated above, in which
a) a solution of the crude phosphonium salt is passed over a bed of an adsorber resin,
b) the adsorber resin is washed with at least one nonpolar solvent and/or at least one electrolyte solution, preferably with at least one nonpolar solvent and at least one electrolyte solution in any sequence, and
c) the phosphonium salt is eluted from the adsorber resin with a polar protic or aprotic solvent.
X is an equivalent of an anion such as halide, e.g. chloride or bromide, sulfate, phosphate, a sulfonate such as benzenesulfonate or toluenesulfonate, C
1
-C
6
-alkanoate, in particular acetate, or hydroxytrifluoroborate.
“C
6
-C
10
-Aryl” is preferably phenyl or tolyl, in particular phenyl.
The radical R is a linear, branched and/or cyclic hydrocarbon radical with 5 to 40 carbon atoms, preferably 10 to 20 carbon atoms, in particular 15 carbon atoms. It may comprise one or two heteroatoms, in particular oxygen atoms. If the radical R comprises a hydroxyl group, this may be protected by conventional hydroxyl protective groups such as those mentioned hereinafter as R″. The process of the invention is particularly suitable for the purification of phosphonium salts employed for synthesizing carotenoids by the Wittig reaction, i.e. those phosphonium salts in which R comprises one to 8 isoprene units, preferably 2 to 4 isoprene units, in particular 3 isoprene units.
Typical examples of R are the following radicals of the formulae Ia-Ik (in which R″ is hydrogen or a hydroxyl protective group, such as acyl, e.g. acetyl, propionyl or benzoyl; alkyl, e.g. methyl, ethyl or t-butyl; silyl, e.g. t-butyldimethylsilyl; or alkoxyalkyl, e.g. 2-methoxy-2-propyl or tetrahydropyranyl):
R is preferably an ionylideneethyl radical. The term “ionylideneethyl” is intended to be understood in its broadest possible meaning and to include all C
15
radicals which are distinguished from naturally occurring ionones by two carbon atoms and/or can be regarded as degradation products of naturally occurring carotenoids. These include, in particular, &psgr;-ionylideneethyl or pseudoionylideneethyl (3,7,11-trimethyldodeca-2,4,6,10-tetraen-1-yl; Ic), &agr;-ionylideneethyl (Id), &bgr;-ionylideneethyl (Ie), 3-hydroxy-4-keto-&bgr;-ionylideneethyl (If, R″=H), 3-hydroxy-&bgr;-ionylideneethyl (Ig, R″=H), 3-hydroxy-&agr;-ionylideneethyl (Ih, R″=H), 4-keto-&bgr;-ionylideneethyl (Ij).
The phosphonium salts can be prepared in a variety of ways. If R is an ionylideneethyl radical, they are expediently obtained by reacting the corresponding vinylionol with at least one mole equivalent of phosphine of the formula PR′
3
in a solvent in the presence of an acid. The vinylionols can in turn be obtained, for example, from ionones by vinyl Grignard reaction.
Thus, a phosphonium salt in which R is a radical of the formula Ic is expediently obtained by reacting 3,7,11-trimethyldodeca-1,4,6,10-tetraen-2-ol with the phosphine and the acid.
The phosphine is preferably used in excess, e.g. 1.1 to 3 equivalents. Triarylphosphines are preferred, and triphenylphosphine is most preferred. The acid is preferably employed in an excess of at least 3, in particular at least 8, equivalents. Suitable acids are C
1
-C
6
-alkanoic acids, boron trifluoride-etherate, hydrochloric acid, hydrobromic acid, phosphoric acid or a sulfonic acid such as benzenesulfonic acid or toluenesulfonic acid. If an alkanoic acid such as acetic acid is used as acid, this is expediently also employed as solvent.
The process of the invention starts from a solution of the crude phosphonium salt in a solvent such as optionally chlorinated or aromatic hydrocarbons, ethers, alcohols or esters, such as hexane, dichloromethane, trichloromethane, benzene, toluene, xylene, diisopropyl ether, tetrahydrofuran, methanol, ethanol and the like. The crude phosphonium salt is particularly preferably dissolved in a C
1
-C
6
-alkanoic acid, in particular acetic acid, or a mixture thereof with water.
The cation exchanger according to the first aspect of the invention is preferably a strongly acidic cation exchanger, which may be macroporous or in gel form, with low or high crosslinkage. Ion exchangers based on polystyrene with sulfo groups have proved particularly suitable. Such ion exchangers are commercially available for example under the name S1468, S100 from Bayer or the name Amberlite IR-120, Amberlite 200 from Rohm and Haas. Before loading of the phosphonium salt to be purified, the cation exchanger is converted into the salt form, i.e. a form in which the anionic groups which are covalently bonded to the resin are associated with metal cations, preferably alkali metal cations, in particular sodium ions. If the cation exchanger is not already in salt form, this can be effected in a simple manner by passing an aqueous solution of a metal hydroxide over the bed of cation exchanger.
The adsorber resin according to the second aspect of the invention preferably has an average pore size of from 50 to 100 Å, in particular 60 to 100 Å. Suitable adsorber resins are, inter alia, those based on polystyrene or polyacrylate. Polyacrylate adsorber resins are preferred. Suitable resins are commercially available under the name XAD2, XAD4, XAD7, XAD16 from Rohm and Haas.
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