Process for the epoxidation of a tetrasubstituted alkene

Abstract

This invention relates to a process for the epoxidation of a tetrasubstituted alkene such as terpinolene to the corresponding epoxide such as terpinolene epoxide by reacting the tetrasubstituted alkene with performic acid prepared in situ from formic acid and hydrogen peroxide in the presence of at least one buffering agent. Further, the invention relates to the use of an oxidizing agent comprising hydrogen peroxide and formic acid for the in-situ epoxidation of a tetrasubstituted alkene.

Claims

1. A process for the epoxidation of a tetrasubstituted alkene to the corresponding epoxide comprising reacting the tetrasubstituted alkene with performic acid prepared in situ from formic acid and hydrogen peroxide in the presence of at least one buffering agent wherein the tetrasubstituted alkene is terpinolene of the formula (Ia) ##STR00007## and the corresponding epoxide is terpinolene epoxide of formula (IIa) ##STR00008##

2. The process according to claim 1 wherein the buffering agent is selected from salts of inorganic acids, salts of organic acids and any combination thereof.

3. The process according to claim 1 wherein the buffering agent is a salt selected from phosphates, formates, acetates, carbonates, citrates, sulfates and any combination thereof.

4. The process according to claim 1 wherein the buffering agent is selected from alkali metal and alkaline earth metal phosphates, alkali metal and alkaline earth metal formates and any combination thereof.

5. The process according to claim 1 wherein the buffering agent is selected from alkali metal phosphates.

6. The process according to claim 1 wherein the buffering agent is selected from di-(alkali metal) hydrogen phosphates.

7. The process according to claim 1 wherein the reaction is carried out in the presence of at least one inert organic solvent.

8. The process according to claim 7 wherein the inert organic solvent is selected from non-halogenated aliphatic hydrocarbons, non-halogenated cycloaliphatic hydrocarbons, non-halogenated aromatic hydrocarbons, halogenated aliphatic hydrocarbons, halogenated aromatic hydrocarbons, amides, ethers, esters, ketones, nitriles and any combination thereof.

9. The process according to claim 7 wherein the inert organic solvent is selected from non-halogenated inert organic solvents.

10. The process according to claim 1 wherein the temperature is from 0 to 70° C.

11. The process according to claim 1 wherein the terpinolene epoxide of formula (IIa) is further converted via limonene-4-ol to terpinene-4-ol.

12. The process according to claim 1, wherein the terpinolene epoxide of formula (IIa), limonene-4-ol or terpinene-4-ol is further converted into (±)-2-exo-(2-Methylbenzyloxy)-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane, any of its individual enantiomers or any non-racemic mixture thereof.

Description

EXAMPLE 1: EPOXIDATION OF TERPINOLENE IN TOLUENE USING DISODIUM HYDROGEN PHOSPHATE (NA.SUB.2.HPO.SUB.4.) AS BUFFERING AGENT

(1) 600 g (4.141 mol) terpinolene (94% w/w) were dissolved in 1200 g toluene in a 4000 ml glass reactor. 240 g (1.673 mol) Na.sub.2HPO.sub.4 (99% w/w) were added in solid form at room temperature. 200 g (4.348 mol) formic acid (100% w/w) were slowly added at 10-15° C. under stirring (start pH: 2.15) before 425 g (6.25 mol) hydrogen peroxide (50% w/w) were dosed in over 6 h at 30° C. (end pH: 2.98). The mixture was stirred over 8 h at 17-18° C.

(2) Phases were separated. 600 ml aqueous K.sub.2SO.sub.3 solution (20% w/w) were added to the organic phase under stirring for peroxide reduction. Phases were separated and the organic phase was extracted with 600 ml aqueous NaOH solution (10%). Finally the organic phase was extracted twice with each 600 ml demineralized water and a sample for quantitative GC analysis was taken: a content of 27.5% terpinolene epoxide equal to a yield of 79.8% was determined.

(3) The organic phase was concentrated (evaporation of toluene) and the distillation sump was distilled over a short column for product purification.

EXAMPLE 2: EPOXIDATION OF TERPINOLENE IN TOLUENE USING SODIUM FORMATE (NAOOCH) AS BUFFERING AGENT

(4) 146.8 g (1.013 mol) terpinolene (94% w/w) were dissolved in 300 g toluene in a 1000 ml glass reactor. 28.4 g (0.405 mol) sodium formate (97% w/w) were added in solid form at room temperature. 47.1 g (1.013 mol) formic acid (99% w/w) were slowly added at <20° C. under stirring before 103.3 g (1.519 mol) hydrogen peroxide (50% w/w) were dosed in over 4 h at 40° C. The mixture was stirred over 8 h at 17° C.

(5) Phases were separated. 150 ml aqueous K.sub.2SO.sub.3 solution (20% w/w) were added to the organic phase under stirring for peroxide reduction. Phases were separated and the organic phase was extracted with 150 ml aqueous NaOH solution (10%). Finally the organic phase was extracted with 150 ml demineralized water and a sample for quantitative GC (gas chromatography) analysis was taken: a content of 23.4% terpinolene epoxide equal to a yield of 71.0% was determined.

EXAMPLE 3: EPOXIDATION OF TERPINOLENE WITHOUT AN INERT ORGANIC SOLVENT

(6) 10 g (0.071 mol) terpinolene (96% w/w) and 3 g (0.043 mol) sodium formate (97% w/w) were mixed at 10-15° C. in a 100 ml glass reactor. 3.3 g (0.072 mol) formic acid (99% w/w) were slowly added at <15° C. under stirring before 7.5 g (0.110 mol) hydrogen peroxide (50% w/w) were dosed in over 15 min at <17° C. The mixture was stirred over 2 h at 15° C., 15 h at 0° C. and 8 h at 10° C. and a sample for HPLC analysis was taken. Product terpinolene epoxide: 69 area-%, starting material terpinolene: 5 area-%.

EXAMPLE 4: EPOXIDATION OF TERPINOLENE IN TOLUENE WITH PARTIAL CONVERSION

(7) 650 g (4.295 mol) terpinolene (90% w/w) was dissolved in 925 g toluene in a 4000 ml glass reactor. 110 g (1.569 mol) sodium formate (97% w/w) were added in solid form at room temperature. 400 g (4.348 mol) formic acid (100% w/w) were slowly added at <20° C. under stirring before 240 g (3.529 mol) hydrogen peroxide (50% w/w) were dosed in over 3 h at 30° C. The mixture was stirred over 17 h at 0° C. and a sample for HPLC analysis was taken. Product terpinolene epoxide: 54 area-%, starting material terpinolene: 36 area-%. Work up was performed similar to example 1. The terpinolene fraction was recycled to a new epoxidation experiment, the terpinolene epoxide forwarded to the next reaction step.

EXAMPLE 5: EPOXIDATION OF TERPINOLENE IN TOLUENE USING DISODIUM HYDROGEN PHOSPHATE (NA.SUB.2.HPO.SUB.4.) AS BUFFERING AGENT

(8) 895.4 g (6.00 mol) terpinolene (91.3% w/w), 1105.8 g (12.00 mol) toluene and 301.26 g (2.10 mol) Na.sub.2HPO.sub.4 (99% w/w) were placed in a glass reactor at 20° C. 279.01 g (6.00 mol) formic acid (99% w/w) were slowly added over 15 minutes under stirring and reaction mixture was heated to 35° C. Then 572.96 g (8.40 mol) hydrogen peroxide (50% w/w) were dosed continuously over 5 h at 35° C. to the reaction mixture under stirring. The reaction mixture was stirred for further 3 h at 35° C.

(9) Water phase was separated and disposed. Then reaction mixture was cooled to 20° C. To the organic phase in the reactor were added 622 g (1.555 mol) sodium hydroxide solution (10% in water) over 30 minutes at 20° C. and mixture was stirred for 1 h at 20° C. Phases were separated.

(10) The lower aqueous phase was disposed. To the organic phase in the reactor were added 622 g demineralized water and mixture was stirred for 1 h at 20° C. Phases were separated.

(11) Organic product phase: 2082.3 g.

(12) A sample for quantitative GC analysis was taken: a content of 35.17% terpinolene epoxide equal to a yield of 80.2% was determined.

COMPARATIVE EXAMPLE 1 (ANALOGOUS TO EP 0032990 A1): EPOXIDATION OF TERPINOLENE IN TOLUENE USING SODIUM FORMATE (NAOOCH) AND ANHYDROUS SODIUM SULFATE AS BUFFERING AGENTS

(13) 149.2 g (1.00 mol) terpinolene (91.3% w/w), 184.3 g (2.00 mol) toluene, 12.1 g (0.084 mol) anhydrous sodium sulfate (Na.sub.2SO.sub.4, 99% w/w) and 7.9 g (0.112 mol) sodium formate (NaOOCH, 97% w/w) were placed in a glass reactor at 20° C. 46.5 g (1.00 mol) formic acid (99% w/w) were slowly added over 15 minutes under stirring and reaction mixture was heated to 35° C. Then 95.5 g (1.4 mol) hydrogen peroxide (50% w/w) were dosed continuously over 5 h at 35° C. to the reaction mixture under stirring. The reaction mixture was stirred for further 3 h at 35° C.

(14) Water phase was separated and disposed. Then reaction mixture was cooled to 20° C. To the organic phase in the reactor were added 104 g (0.26 mol) sodium hydroxide solution (10% in water) over 30 minutes at 20° C. and mixture was stirred for 1 h at 20° C. Phases were separated. The lower aqueous phase was disposed. To the organic phase in the reactor were added 103.7 g demineralized water and mixture was stirred for 1 h at 20° C. Phases were separated.

(15) Organic product phase: 322.3 g.

(16) A sample for quantitative GC analysis was taken: a content of 11.0% terpinolene epoxide equal to a yield of 23.3% was determined.