Organic compounds

Abstract

An allylic oxidation process includes forming a mixture containing -Guaiene and an iron (III)-X porphyrin complex catalyst in a sustainable solvent, introducing molecular oxygen into the mixture, and effecting allylic oxidation to produce an ,-unsaturated ketone, Rotundone.

Claims

1. An allylic oxidation process comprising: forming a mixture containing a-Guaiene and an iron (III)-X porphyrin complex catalyst, wherein X is selected from the group consisting of CI, Br, I, mesylates, triflates, and carboxylates, in a sustainable solvent, introducing molecular oxygen into the mixture, and effecting allylic oxidation to produce an ,-unsaturated ketone, Rotundone.

2. The process according to claim 1, wherein the mixture additionally contains a base coordination compound.

3. The process according to claim 1, including exposing the mixture to electromagnetic radiation.

4. The process according to claim 1, wherein the sustainable solvent is selected from the group consisting of water, acetone, ethanol, 2-propanol, ethyl acetate, isopropyl acetate, methanol, methyl ethyl ketone, 1-butanol, t-butanol and mixtures thereof.

5. The process according to claim 1, wherein the sustainable solvent is selected from the group consisting of cyclohexane, heptane, toluene, methylcyclohexane, methyl t-butyl ether, isooctane, acetonitrile, xylenes, dimethyl sulfoxide, acetic acid, ethylene glycol and mixtures thereof.

6. The process according to claim 1, wherein the catalyst is an iron (III) porphyrin complex catalyst, having a chloride counter-ion.

7. The process according to claim 1, wherein the porphyrin complex is a tetraphenylporphyrin complex.

8. The process according to claim 1, wherein the catalyst is selected from chloro(tetraphenylporphyrinato)iron(III) and hemin chloride.

9. The process according to claim 2, including exposing the mixture to electromagnetic radiation.

10. The process according to claim 4, wherein the sustainable solvent is selected from the group consisting of cyclohexane, heptane, toluene, methylcyclohexane, methyl t-butyl ether, isooctane, acetonitrile, xylenes, dimethyl sulfoxide, acetic acid, ethylene glycol and mixtures thereof.

11. The process according to claim 2, wherein the catalyst is an iron (III) porphyrin complex catalyst, having a chloride counter-ion.

12. The process according to claim 3, wherein the catalyst is an iron (III) porphyrin complex catalyst, having a chloride counter-ion.

13. The process according to claim 4, wherein the catalyst is an iron (III) porphyrin complex catalyst, having a chloride counter-ion.

14. The process according to claim 5, wherein the catalyst is an iron (III) porphyrin complex catalyst, having a chloride counter-ion.

15. The process according to claim 11, wherein the porphyrin complex is a tetraphenylporphyrin complex.

16. The process according to claim 12, wherein the porphyrin complex is a tetraphenylporphyrin complex.

17. The process according to claim 13, wherein the porphyrin complex is a tetraphenylporphyrin complex.

18. The process according to claim 14, wherein the porphyrin complex is a tetraphenylporphyrin complex.

19. The process according to claim 2, wherein the catalyst is selected from chloro(tetraphenylporphyrinato)iron(III) and hem in chloride.

20. The process according to claim 3, wherein the catalyst is selected from chloro(tetraphenylporphyrinato)iron(III) and hem in chloride.

21. The process according to claim 4, wherein the catalyst is selected from chloro(tetraphenylporphyrinato)iron(III) and hem in chloride.

22. The process according to claim 5, wherein the catalyst is selected from chloro(tetraphenylporphyrinato)iron(III) and hem in chloride.

23. The process according to claim 6, wherein the catalyst is selected from chloro(tetraphenylporphyrinato)iron(III) and hem in chloride.

Description

EXAMPLE 1. PREPARATION OF ROTUNDONE 2 FROM -GUAIENE 1 UNDER FE(III)-CATALYSIS AND LIGHT IRRADIATION (PHOTOCATALYTIC)

(1) Chloro(tetraphenylporphyrinato)iron(III) (34 mg, 0.05 mmol) and imidazole (6.7 mg, 0.1 mmol) were added to -Guaiene 91% (1 g, 4.5 mmol) in a 1:1 ethanol/water mixture (20 ml), under stirring. Oxygen was bubbled into the greenish turbid mixture which was stirred at 45 C. under light irradiation with a 300 W Osram Ultra Vitalux lamp until complete conversion was detected (8-16 hours). The product distribution contained Rotundone 2 (31%), ketone 5 (9%), hydroxy-Rotundone 6 (16%) and Corymbolon 7 (1%). The green-brown turbid mixture was partially evaporated under reduced pressure and the residue extracted with tert-butyl methyl ether. The combined organic layers were dried over MgSO.sub.4, filtered and evaporated. The residual brown oil (1.22 g) was bulb-to-bulb distilled at 150-230 C./0.045 mbar, giving 0.63 g Rotundone 2 of 45% GC-purity (29% corr. yield) and 0.39 g of a residue.

EXAMPLE 2. PREPARATION OF ROTUNDONE 2 FROM -GUAIENE 1 UNDER FE(III)-CATALYSIS IN THE DARK (LIGHT EXCLUSION)

(2) Chloro(tetraphenylporphyrinato)iron(III) (34 mg, 0.05 mmol) and imidazole (6.7 mg, 0.1 mmol) were added to -Guaiene 91% (1 g, 4.5 mmol) in a 1:1 ethanol/water mixture (20 ml) under stirring. Oxygen was bubbled into the greenish turbid mixture at 45 C. The reaction flask was wrapped with an aluminum foil to exclude light. After 8 hours GCMS indicated complete conversion to a mixture comprising Rotundone 2 (25%), Rotundol 3 (1%), Epoxy-Guaiene 4 (4%), ketone 5 (5%), and hydroxy-Rotundone 6 (20%). The green-brown turbid mixture was evaporated partially under reduced pressure and the residue extracted with tert-butyl methyl ether. The combined organic layers were dried over MgSO.sub.4, filtered and evaporated. The residual brown oil (1.22 g) was bulb-to-bulb distilled at 150-230 C./0.045 mbar, giving 0.77 g Rotundone 2 of 43% GC-purity (34% corr. yield) and 0.24 g of a residue.

EXAMPLE 3. PREPARATION OF ROTUNDONE 2 FROM -GUAIENE 1 UNDER FE(III)-CATALYSIS AND AIR

(3) Air was bubbled into a greenish turbid mixture of chloro(tetraphenylporphyrinato)iron(III) (34 mg, 0.05 mmol), imidazole (6.7 mg, 0.1 mmol) and -Guaiene 91% (1 g, 4.5 mmol) in a 1:1 ethanol/water mixture (20 ml) under stirring and at 45 C. After 49 hours, GCMS indicated 96% conversion to a mixture comprising Rotundone 2 (21%), epoxy-Guaiene 4 (5%), ketone 5 (4%), hydroxy-Rotundone 6 (10%), and Corymbolon 7 (1%). After evaporation of the ethanol under reduced pressure the dark mixture was extracted with tert-butyl methyl ether against water. The combined organic layers were dried over MgSO.sub.4, filtered and evaporated to 1.3 g of a brownish residue, which was purified by bulb-to-bulb distillation at 150-230 C./0.025 mbar giving 0.76 g of Rotundone 2 with 41% GC-purity (32% corr. yield) and 0.28 g of a residue.

EXAMPLES 4-12. PREPARATION OF ROTUNDONE 2 FROM -GUAIENE 1 UNDER FE(III)-CATALYSIS IN VARIOUS SOLVENTS OR MIXTURES OF SOLVENTS

(4) Examples 4 through 12 demonstrate the allylic oxidation of 1 g -Guaiene 1 (91%) to the ketone (Rotundone 2) in a mixture with 1% ((chloro(tetraphenylporphyrinato)iron(III))) and 2% imidazole.

(5) General conditions included use of 20 ml solvent or mixture of solvents at 45 C. There was no intentional irradiation of, or light exclusion of the mixture, unless otherwise indicated.

(6) TABLE-US-00001 TABLE 1 product distribution [%] Oxygen- compound No. 2 dist. purity 2 Ex. Solvent.sup.b Time [h] addition 1 2 3 4 5 6 7 corr..sup.a dist. 4 EtOH/H.sub.2O 8 gas inlet 25 1 4 5 20 34% 43% 5 EtOH/H.sub.2O 4 balloon 29 1 5 6 13 1 27% 30% 6 H.sub.2O 24 gas inlet 30 1 4 5 24 1 20% 32% 7 iPrOH/H.sub.2O 8 gas inlet 28 6 13 17 1 18% 28% 8 MeOH/H.sub.2O 12 gas inlet 29 1 4 4 16 20% 28% 9 EtOH/H.sub.2O 30 balloon 25 16 13 6 1 22% 25% 3:1 10 EtOH/H.sub.2O 23 balloon 27 4 4 18 20% 27% 1:3 11 EtOH 30 balloon 2 23 20 5 4 18% 21% 12 MeCN/H.sub.2O 7 balloon 24 16 13 8 20% 27% 3:1 .sup.aMolar yield (in mol %) after distillation (corrected by purity of product after distillation and substrate purity). .sup.bsolvent mixtures are 1:1 if not otherwise indicated.

(7) Compounds: -Guaiene 1, Rotundone 2, Rotundol 3, epoxy-Guaiene 4, ketone 5, hydroxy-Rotundone 6, and Corymbolon 7.

(8) Bubbling molecular oxygen through the mixture appears advantageous over introduction of the molecular oxygen via balloon.

EXAMPLES 13-15. PREPARATION OF ROTUNDONE 2 FROM -GUAIENE 1 UNDER FE(III)-CATALYSIS WITH VARIOUS LIGANDS

(9) Examples 13 through 15 demonstrate the allylic oxidation of -Guaiene 1 to the ketone (Rotundone 2) with iron porphyrin catalysts having different substituted porphyrin ligands. General conditions included mixing 1 g -Guaiene 1 (91%), 1 mol % iron porphyrin catalyst, 2 mol % imidazole, with molecular oxygen being introduced through an inlet into 20 ml of a EtOH/H.sub.2O solvent mixture at a molar ratio of 1:1, at 45 C. Percentages of compounds 1-7 were determined by GCMS after isolation.

(10) TABLE-US-00002 TABLE 2 Product distribution [%] time Compound No. 2 dist. purity Ex. Fe-porphyrin catalyst [h] 1 2 3 4 5 6 7 corr..sup.b 2 dist. 13 Fe-porphyrin.sup.a 8 25 1 4 5 20 34% 43% 14 Fe-(pentafluorophenyl) 26 30 10 2 13 27% 31% porphyrin (CAS 36965-71-6) 15 Fe-(p-methoxyphenyl) 31 1 29 1 3 5 19 1 10% 13% porphyrin (CAS 36995-20-7) .sup.aFe-porph (chloro(tetraphenylporphyrinato)iron(III)). .sup.bMolar yield (in mol %) after distillation (corrected by purity of product after distillation and substrate purity)

EXAMPLES 16-19. PREPARATION OF ROTUNDONE 2 FROM -GUAIENE 1 UNDER FE(III)-CATALYSIS AT VARIOUS TEMPERATURES

(11) Examples 16 through 19 demonstrate the allylic oxidation of 1 g -Guaiene 1 (91%) to the ketone (Rotundone 2) in a mixture with 1% Fe-porphyrin and 2% Imidazole at various temperature conditions. General conditions included bubbling O.sub.2 through an inlet for 30 minutes, then providing an O.sub.2 atmosphere with a balloon, with 1000 rpm mixing of the mixture in 20 ml solvent EtOH/H.sub.2O (1:1). Percentages of compounds 1-7 were determined by GCMS.

(12) TABLE-US-00003 TABLE 3 Product distribution [%] Compound No. Ex. T C. time [h] 1 2 3 4 5 6 7 2 dist. corr..sup.a purity 2 dist. 16 0-25 C. 24 32 2 3 13 28% 30% 17 25 C. 7 32 1 3 4 13 1 24% 27% 18 45 C. 8 25 1 4 5 20 34% 43% 19 80 C. 23.5 31 2 12 21 1 22% 41% .sup.aMolar yield (in mol %) after distillation (corrected by purity of product after distillation and substrate purity)

EXAMPLE 20: PREPARATION OF ROTUNDONE 2 FROM -GUAIENE 1 AT LARGER SCALE

(13) Oxygen was bubbled into a greenish turbid mixture of chloro(tetraphenylporphyrinato)-iron(III) (172 mg, 0.245 mmol), imidazole (67 mg, 1 mmol) and -Guaiene 91% (10 g, 45 mmol) in a 1:1 ethanol/water mixture (200 ml) under stirring and at 45 C. After 1 h the oxygen inlet was replaced by an oxygen balloon. After another 7 h stirring at 45 C. GCMS indicated a quantitative conversion to a mixture comprising Rotundone 2 (30%), epoxy-Guaiene 4 (3%), ketone 5 (7%), hydroxy-Rotundone 6 (13%), and Corymbolon 7 (1%). After evaporation of the ethanol under reduced pressure the dark brown mixture was extracted with tert-butyl methyl ether against water. The combined organic layers were dried over MgSO.sub.4, filtered and evaporated giving 14.3 g of a brownish residue, which was purified by bulb-to-bulb distillation at 150-230 C./0.1 mbar giving 8.6 g of Rotundone 2 with 38% GC-purity (33% corr. yield) and 2.3 g of a brown residue.