Production of farnesol

Abstract

The present invention relates to an improved way for the production of farnesol.

Claims

1. A process for the production of the compound of formula (I): ##STR00011## wherein the process comprises the steps of: (1) reacting a compound of formula (II): ##STR00012## by a rearrangement process in the presence of: (i) at least one mononuclear vanadium catalyst having the following formula: ##STR00013## wherein R is an alkyl or aryl group or a M(R.sub.1).sub.3 group, where M is Si, Sn or Ge and R.sub.1 is an alkyl or aryl group, and wherein the catalyst is present in a weight ratio of the compound of formula (II) to the catalyst in a range of 10:1 to 500:1, and (ii) 0.001 to 0.015 mol equivalent relative to the compound of formula (II) at least one least one saturated fatty acid with a 16-22 carbon chain selected from the group consisting of stearic acid, palmitic acid, arachidic acid and behenic acid to thereby form a compound of formula (III): ##STR00014## and thereafter (2) conducting hydrogenation of the compound of formula (III) to the compound of formula (I).

2. The process according to claim 1, wherein the mononuclear vandium catalyst is at least one catalyst compound selected from the group consisting of: ##STR00015##

3. The process according to claim 1, wherein the reaction of step (1) is carried out in at least one non-polar aprotic solvent.

4. The process according to claim 3, wherein the at least one non-polar aprotic solvent is selected from aliphatic solvents having a boiling point above 280 C., and aromatic solvents.

5. The process according to claim 1, wherein the reaction of step (1) is carried out at a temperature between 30 C. and 180 C.

6. The process according to claim 1 wherein the hydrogenation of step (2) is carried out with H.sub.2 gas.

7. The process according to claim 1, wherein the hydrogenation of step (2) is a transfer hydrogenation.

8. The process according to claim 7, wherein the transfer hydrogenation is carried out in the presence of at least one metal-complex, wherein the metal is selected from the group consisting of Ir, Rh and Ru.

9. The process according to claim 8, wherein the metal-complex is selected from the group consisting of pentamethylcyclopentadienyl Ir-complex (Cp*Ir), pentamethylcyclopentadienyl Rh-complex (Cp*Rh) and Ru-arene-complexes.

10. The process according to claim 8, wherein the metal-complex also comprises at least one organic ligand which comprises at least one N and/or P atom.

11. The process according to claim 10, wherein the at least one organic ligand comprises 1,2 amino alcohols and/or mono-sulfonated 1,2-diamines.

12. The process according to claim 7, wherein the transfer hydrogenation is carried out in the presence of at least one alcohol or a salt thereof, formic acid or a salt thereof or a formic acid/trimethylamine complex.

13. The process according to claim 4, wherein the solvent is xylene or toluene.

14. The process according to claim 9, wherein the metal-complex is a Ru-p-cymene complex or a Ru-benzene complex.

Description

EXAMPLES

Example 1

(1) E,Z-dehydronerolidol to (2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesol (step (1)) 36.6 g (0.163 Mol) of E,Z-dehydronerolidol, and 465 mg (1.63 mMol) of stearic acid, and 5.90 g (0.212 Mol) of triphenylsilanol, and 2.95 g (3.26 mMol) of tris-(triphenylsiloxy)-vanadium oxide and 163 g of vacuum pump oil were weighed into the 350 ml four-necked flask.

(2) The reaction mixture was heated up to 140 C. under a slight argon overflow.

(3) The reaction mixture was stirred for five hours. Afterwards the reaction mixture was cooled down to room temperature and the product ((2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesal) was obtained by distillation in a yield of 82.6%. The amount of the 4 ((2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesal isomers were (32 wt-%, 24 wt-%, 25 wt-%, 19 wt-%).

Example 2

(4) The same reaction as in Example 1 was carried out but instead of vacuum pump oil xylenes was used as a solvent.

(5) The yield ((2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesal was 82.2%. The amount of the 4 ((2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesal isomers were (34 wt-%, 24 wt-%, 25 wt-%, 17 wt-%)

Example 3

(6) The same reaction as in Example 1 was carried out, but without stearic acid.

(7) The yield ((2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesal was 79.9%. The amount of the 4 ((2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesal isomers were (29 wt-%, 19 wt-%, 31 wt-%, 21 wt-%)

Example 4

(8) E-dehydronerolidol to (2E/6E, 2Z/6E)-farnesol

(9) The same reaction as in Example 1 was carried out, but E-dehydronerolidol was used as starting material.

(10) The yield (2E/6E, 2Z/6E)-farnesal was 89.2%. The amount of the 2 (2E/6E, 2Z/6E)-farnesal isomers were (52 wt-%, 48 wt-%)

Example 5

(11) (2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesal to (2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesol (step (2))

(12) In a 25 ml round bottomed flask with magnetic stirrer and argon overlay 12.3 mg (0.02 mMol) of dichloro(p-cymene)ruthenium(II) dimer and 9.5 mg (0.044 mMol) of N-(2-aminoethyl)-4-methylbenzenesulfonamide were solved in 9 ml (8.05 g; 91 mMol) of ethyl acetate under stirring for 30 minutes at room temperature.

(13) Afterwards 1.74 g (20 mMol) of formic acid triethylamine complex 5:2 and then 1.07 g (4.9 mMol) of farnesal (2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesal) (obtained from example 1) were weighed in. The solution was stirred for 20 hours at RT.

(14) (2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesol was obtained in yield of 98%. The amount of the 4 (2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesal isomers were (28 wt-%, 25 wt-%, 25 wt-%, 22 wt-%)

Example 6

(15) (2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesal to (2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesol (step (2))

(16) In a 250 ml flask with magnetic stirrer and argon overlay 8.75 g (32.6 mMol) of farnesal ((2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesal) (obtained by example 1) and 6.66 mg (23.6 mMol) of triisopropoxyaluminum were solved in 20.5 g (342 mMol) of isopropanol. The reaction mixture was stirred under reflux at a temperature of 98 C. for 19 h.

(17) Afterwards (2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesol was obtained by extraction at yield of 81.4%. The amount of the 4 (2E/6E, 2Z/6E, 2E/6Z, 2Z/6Z)-farnesal isomers were (29 wt-%, 25 wt-%, 25 wt-%, 21 wt-%)

Example 7

(18) (2E/6E, 2Z/6E)-farnesal to (2E/6E, 2Z/6E)-farnesol (step (2))

(19) The same reaction as in Example 5 was carried out, but (2E/6E, 2Z/6E)-farnesal from Example 4 was used as starting material.

(20) The yield (2E/6E, 2Z/6E)-farnesol was 86.2%. The amount of the 2 (2E/6E, 2Z/6E)-farnesol isomers were (52 wt-%, 48 wt-