QUINONES AND PROCESS OF OBTAINING SAME

Abstract

Disclosed is a process for the oxidation of at least one chroman (C1) in a solvent mixture comprising at least two solvents or in a C-bearing solvent, with a gaseous compound comprising, essentially consisting of, or consisting of oxygen in the presence of a copper catalyst, said copper catalyst exhibiting the oxidation state (+1) or (+2). A further part of the disclosure is a composition comprising at least one chroman (C1) and/or at least one quinone (C30), a solvent mixture comprising at least two solvents or a C-bearing solvent, a copper catalyst, said copper catalyst exhibiting the oxidation state (+1) or (+2) and a gaseous compound comprising, essentially consisting or consisting of oxygen. A quinone preparation and a process of making same is also part of the invention.

Claims

1.-22. (canceled)

23. Process for the oxidation of at least one chroman (C1) ##STR00061## with R1, R3, R4, R5 being H or CH.sub.3, R2 being OH, OAc, OCOC.sub.1-C.sub.18-alkyl, and R6 being alkyl, alkenyl, in a solvent mixture comprising at least two solvents or in a C-bearing solvent, with a gaseous compound comprising oxygen in the presence of a copper catalyst, said copper catalyst exhibiting the oxidation state (+1) or (+2).

24. The process according to claim 23, wherein the gaseous compound comprising oxygen is actively moved through the solvent mixture comprising at least two solvents or through the C-bearing solvent.

25. The process according to claim 23, wherein the copper catalyst is used in an amount ranging from 0,001 to 10 molar equivalents with respect to the molar amount of chroman (C1) used.

26. The process according to claim 23, wherein the copper catalyst is a copper halide.

27. The process according to claim 23, wherein the copper catalyst is combined with at least one metal compound selected form the group consisting of Na, Li, K, Cs, Mg, Ca, Sr, Ba, Fe, Cr, Mn, Co, Ni, Zn, La, Ce, Pr, Nd compounds.

28. The process according to claim 23, wherein the chroman (C1) is at least one of the group consisting of -tocopherol of formula (C3), (C4), (C5) and -tocotrienol of formula (C12), (C13), (C14).

29. The process according to claim 23, wherein the solvent mixture comprising at least two solvents or the C-bearing solvent is free of any detergent.

30. The process according to claim 23, wherein the at least two solvents of the solvent mixture comprise water and an organic solvent.

31. The process according to claim 30, wherein the at least two solvents of the solvent mixture comprise as organic solvent at least one primary alcohol or at least one secondary alcohol or a mixture of at least one primary and at least one secondary alcohol

32. The process according to claim 30, wherein the weight ratio of the organic solvent to water ranges from 0.01:1 to 499:1.

33. Composition comprising: a) at least one chroman (C1) ##STR00062## with R1, R3, R4, R5 being H or CH.sub.3, R2 being OH, OAc, OCOC.sub.1-C.sub.18-alkyl, and R6 being alkyl, alkenyl and/or at least one quinone (C30) ##STR00063## with R7, R8, R10 being H or CH.sub.3; R9 being alkyl, alkenyl; b) a solvent mixture comprising at least two solvents or a C-bearing solvent; c) a copper catalyst, said copper catalyst exhibiting the oxidation state (+1) or (+2); d) a gaseous compound comprising, essentially consisting or consisting of oxygen; said composition being obtained by the process according to claim 23.

34. Composition according to claim 33, wherein the gaseous compound in the composition is in the form of gas bubbles, the amount of which is higher than that amount, which is obtained, when a) to c) are combined and stored under ambient air.

35. Process for obtaining a quinone preparation comprising the steps: i) removing one solvent from the solvent mixture comprising at least two solvents of the composition of claim 33, or removing the C-bearing solvent of the composition of claim 33; with optionally adding hydrochloric acid prior or during removing one solvent from the solvent mixture or removing the C-bearing solvent; iia) distilling off remaining solvent(s) or iib) degassing the composition or iic) distilling off remaining solvent(s) and degassing the composition; iii) applying the composition of step iia), step iib) or step iic) onto a separation means, the diameter of the surface of said separation means being larger than the height of said separation means; iv) optionally subjecting the remainder from step iii) to a further distillation, or i) removing one solvent from the solvent mixture comprising at least two solvents of the composition of claim 33, or removing the C-bearing solvent of the composition of claim 33. with optionally adding hydrochloric acid prior or during removing one solvent from the solvent mixture or removing the C-bearing solvent; iia) distilling off remaining solvent(s) or iib) degassing the composition or iic) distilling off remaining solvent(s) and degassing the composition; iii) applying the composition of step iia), step iib) or step iic) to another distillation step; iv) optionally subjecting the remainder from step iii) to a further distillation, or i) removing one solvent from the solvent mixture comprising at least two solvents of the composition of claim 33, or removing the C-bearing solvent of the composition of claim 33 with optionally adding hydrochloric acid prior or during removing one solvent from the solvent mixture or removing the C-bearing solvent; iia) distilling off the remaining solvent(s); or iib) degassing the composition; or iic) distilling off remaining solvent(s) and degassing the composition; iii) applying the composition of step iia), step iib) or step iic) onto a separation column; iv) optionally subjecting the remainder from step iii) to a further distillation.

36. The process according to claim 35, wherein after step i) it comprises: ia) reducing the volume of the removed one solvent from the composition and/or; ib) adding hydrochloric acid to said removed one solvent; ic) storing or reinjecting the thus obtained mixture of step ia) or ib), or id) adding hydrochloric acid to the removed one solvent from the composition and/or; ie) reducing the volume of the mixture obtained in step id); if) storing or reinjecting the thus obtained mixture of step id) or ie).

37. The process according to claim 35, wherein the separation means or the separation column comprises a solid support, said solid support being selected from at least one of silica, silica based material also named modified silica, zeolite, aluminum oxide, alumina silicates, carbon, carbon based materials, carbohydrate, polymeric organic materials, acrylic polymers, ascorbic acid, tetrasodium iminodisuccinate, citric acid, dicarboxymethylglutamic acid, ethylenediaminedisuccinic acid (EDDS), ethylenediaminetetraacetic acid (EDTA), methylene phosphonic acid, malic acid, or nitrilotriacetic acid (NTA), preferably being silica.

38. The process according to claim 37, wherein the solid support, preferably silica, has a particle size ranging from 5 m to 1000 m; and a mean pore size ranging from 1 to 100 nm.

39. The process according to claim 37, wherein the solid support is suspended in a suspending solvent or a mixture of suspending solvents selected from the group consisting of aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, carboxylic acids, esters, alcohols, ethers, ketones, acetals, ketals, nitriles, dimethyl sulfoxide, formamide, dimethylformamide and water; the slurry thus obtained is applied to the separation means or to the separation column.

40. The process according to claim 35, wherein the composition after step iia), step iib) or step iic) is dissolved or suspended in a diluting solvent or diluting solvent mixture selected from the group consisting of aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, carboxylic acids, esters, alcohols, ethers, ketones, acetals, ketals, nitriles, dimethyl sulfoxide, formamide, dimethylformamide and water, and the diluted composition thus obtained is subjected to step iii).

41. The process according to claim 35, wherein iii) after applying the composition of step iia), iib) or step iic) onto the separation means, the diameter of the surface of said separation means being larger than the height of said separation means or after applying the composition of step iia), iib) or step iic) onto the separation column; iiia) one elutes impurities and by-products with a mixture of a non-polar and a polar solvent having a volumetric ratio ranging from 90:10 to 99:1; iiib) one elutes the product with a mixture of a non-polar and a polar solvent having a volumetric ratio ranging from 60:40 to 85:15; iv) optionally one subjects the remainder from step iiib) to a further distillation or, iii) after applying the composition of step iia), iib) or step iic) onto the separation means, the diameter of the surface of said separation means being larger than the height of said separation means or after applying the composition of step iia), iib) or step iic) onto the separation column; iiia) one elutes the product with a mixture of a non-polar and a polar solvent having a volumetric ratio ranging from 60:40 to 85:15; iiib) one elutes impurities and by-products with a mixture of a non-polar and a polar solvent having a volumetric ratio ranging from 90:10 to 99:1; iv) optionally one subjects the remainder from step iiia) to a further distillation.

42. The process according to claim 41, wherein the non-polar solvent is at least one of heptane or cyclohexane, the polar solvent is at least one of isopropylacetate or ethylacetate and the mixture of the non-polar solvent and the polar solvent comprises at least one polar solvent and at least one non-polar solvent.

43. Quinone preparation obtained by the process according to claim 35 comprising: A) 90 to 100 w % of quinone (C30) ##STR00064## with R7, R8, R10 being H or CH.sub.3; R9 being alkyl, alkenyl; B) 0,0001 to 9999/1000 ppm of Cu; C) 0,0001 to 100 ppm of organic chlorine; D) minor components with minor components being all chemical entities besides those mentioned under A), B) and C) which at most amount up to 10 w % minus the amount of components B) and C), and with the sum of A) to D) not exceeding 100 w %.

44. An animal nutrition composition, dietary supplement, or beverage additive comprising the quinone preparation according to claim 43.

Description

CN1, EXAMPLE 1052

Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0491] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,15 g (1.56 mol) of water and placed in the reactor. 144,20 g (312.51 mmol) of -tocopherol of formula C5 were solubilized in 386,38 g (3.8 mol) of 3-hexanol and added to the reactor. The reaction mixture was maintained at 25 C. while bubbling 40 l/h of air through it for a period of 4,75 h (altogether being an embodiment of the inventive composition). The aqueous phase was removed. The organic phase was washed three times with water at 48 C. and the at least one solvent or the C-bearing solvent of the organic phase removed under reduced pressure. 150,9 g of crude -tocopherol quinone of formula C33 (MW=446.71 g/mol) corresponding to a yield of 94,1% were obtained.

CN2, EXAMPLE 1053

[0492] Purification of Sample from CN1 by Degassing

[0493] 148,6 g of crude -tocopherol quinone of formula C33 were subjected to a reduced pressure of 2,310.sup.2 Pa and a temperature of 110 C. for 155 min, after which 132,8 g of -tocopherol quinone of formula C33 were obtained. The amount of organic chlorine was 73 ppm, of chloride was 47 ppm and of Cu ions was 70 ppm.

CN3, EXAMPLE 1056

[0494] Further purification of sample from CN2 by application onto a short-plug as separation means

[0495] A G3 glass suction filter (volume of 1 l, 12.5 cm inner diameter) was filled with a slurry of silica (particle size 40 to 63 m) in n-heptane to a height of 6.7 cm giving a volume of 822 ml. 35,5 g of -tocopherol quinone of formula C33 from CN2 (example 1053) were dissolved in 14,2 g of n-heptane and applied onto the wet silica. Under suction another 1000 ml of n-heptane were added. Thereafter elution was realized two times with 2.428 g of a solution of n-heptane comprising 3 w % of isopropyl acetate yielding fractions 1 and 2 followed by one elution with 2.428 g of a solution of n-heptane containing 20 w % of isopropyl acetate yielding fraction 3. Said fraction 3 was freed from solvent and dried to give 34,0 g of -tocopherol quinone of formula C33 (quinone preparation of the invention). The amount of organic chlorine in said quinone preparation was 18 ppm, the amount of chloride <3 ppm and the amount of Cu was <3 ppm.

CN4, COMPARATIVE EXAMPLE 384

Reaction of Chroman C1 in the Absence of Catalyst

[0496] 25 g (58.04 mmol) of -tocopherol of formula C5 were solubilized in 225 g of dimethylformamide and the reaction mixture supplemented with 30 l/h of air for 6 h at room temperature. Thereafter 0,8 g (5.8 mmol) of potassium bicarbonate were added with stirring and 30 l/h of air was added for another 24 h. Potassium bicarbonate was filtered off and a sample taken for HPLC analysis. No quinone C30 could be detected.

CN5, COMPARATIVE EXAMPLE 389

Reaction of Chroman C1 in the Absence of Catalyst

[0497] 32 g (74.29 mmol) of -tocopherol of formula C5 were solubilized in 92,27 g of n-hexanol and the reaction mixture supplemented with 30 l/h of air for 6 h at room temperature. A sample was taken for HPLC analysis. No quinone C30 could be detected.

CN6, COMPARATIVE EXAMPLE 1023

[0498] Reaction of Chroman C1 without Actively Moving a Gaseous Compound Containing Oxygen Through the Reactor

[0499] 55,0 g (120 mmol) of -tocopherol of formula C3 or C5 were solubilized in 550 ml solvent. 5,12 g (30.0 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were added. The mixture was left standing under air for 8 h. Afterwards in the case of the solvent methanol 200 ml of cyclohexane and 100 ml of water were added, in the case of the solvent n-hexanol 200 ml of water were added. The phases were separated. The organic phase was washed with water and the respective yield was determined from the organic phase by HPLC-w % as described in the Table 12.

TABLE-US-00013 TABLE 12 R,R,R--tocopherol rac--tocopherol quinone of quinone of formula C33 formula C32 Yield [%] Yield [%] Solvent Methanol n-Hexanol Methanol n-Hexanol 0.25 eq CuCl.sub.2 2 H.sub.2O 5.2 2.7 3.5 2.4

CN7, COMPARATIVE EXAMPLE 1004

[0500] Reaction of Chroman C1 without Actively Moving a Gaseous Compound Containing Oxygen Through the Reactor

[0501] 1,0 g (2.32 mmol) of -tocopherol of formula C3 or C5 was respectively solubilized in 10 ml solvent and each mixture placed in a distinct 100 ml Erlenmeyer flask. 1,0 g, (37.2 mmol) of CuCl.sub.2, CAS no: 7447-39-4 was added to each mixture. Each flask was placed on a shaker set at a speed of 40 rpm at room temperature and shaken for 8 h or 16 h respectively. After 8 h or 16 h the reaction mixture was filtered over 1,5 g silica to remove CuCl.sub.2. The silica was washed with the solvent used for the reaction. The yields determined by HPLC-w % in the solution after filtration are described in Table 13.

TABLE-US-00014 TABLE 13 R,R,R--tocopherol quinone of rac--tocopherol quinone of formula C33 formula C32 Yield [%] Yield [%] Solvent Methanol n-Hexanol Methanol n-Hexanol 8 h 14.6 17.0 13.2 10.1 16 h 31.7 17.6 32.0 18.6

CN8, COMPARATIVE EXAMPLE 903

[0502] Reaction of Chroman C1 without Actively Moving a Gaseous Compound Containing Oxygen Through the Reactor

[0503] 5,0 g (11.00 mmol) of -tocopherol of formula C5 were solubilized in 39,5 g of methanol and 5,0 g, (37.19 mmol) of CuCl.sub.2, CAS no: 7447-39-4 were added. The whole was stirred for 48 h at room temperature. 20 ml of cyclohexane and 25 ml of bi-distilled water were added. The organic phase was washed two times with 25 ml of bi-distilled water and the solvent of the unified organic phases was removed under reduced pressure. 5,8 g of a crude product were obtained containing 4,59 w % of quinone of formula C33. This corresponds to a yield of 5,4% as determined by HPLC.

CN9, COMPARATIVE EXAMPLE 1015

[0504] Reaction of Chroman C1 without Actively Moving a Gaseous Compound Containing Oxygen Through the Reactor

[0505] 55,0 g (94,0%, 120 mmol) of rac--tocopherol of formula C3 were solubilized in 550 ml of the respective solvent. 5,12 g (30.0 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were added respectively. Each mixture was stirred with a speed of 100 rpm. After 8 h in the case of methanol as solvent, 200 ml of cyclohexane and 100 ml of water, in the case of n-hexanol as solvent, 200 ml of water were added to each mixture. The phases separated. The organic phase obtained from each mixture was washed with water and the yields were determined in each organic phase by HPLC-w % as shown in the Table 14.

TABLE-US-00015 TABLE 14 rac--tocopherol quinone of formula C32 Yield [%] Solvent Methanol n-Hexanol 0.25 eq CuCl.sub.2 2 H.sub.2O 9.5 9.9

CN10, EXAMPLE 968

Use of an Appropriate Amount of Catalyst, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0506] 1,69 g (9.91 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were solubilized in 15 g (0.83 mol) of water and placed in the reactor together with 83 g of n-hexanol. A solution of 44,90 g (98.93 mmol) of -tocopherol of formula C3 in 39,9 g of n-hexanol was added dropwise at 25 C. during 4 h. The mixture was stirred for another 8 h. During the whole reaction air at a rate of 12 to 14 l/h was bubbled through the reaction mixture while stirring with 1200 rpm. After termination of the reaction 54 ml of bi-distilled water were added to the mixture and the phases were separated. The organic phase was washed twice with 54 ml of bi-distilled water. A sample of the organic phase was taken and revealed a yield of 92,8% of -tocopherol quinone of formula C32 as determined by HPLC.

CN11, EXAMPLE 952

Use of an Appropriate Amount of Catalyst, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0507] 4,22 g (24.75 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 and 4,19 g (98.85 mmol) of LiCl, CAS no: 7447-41-8 were dissolved in 35,7 g of bi-distilled water, supplemented with 33 g of n-hexanol and placed in the reactor. A solution of 90 g n-hexanol containing 42,15 g (98.83 mmol) of -tocopherol of formula C3 was added dropwise at room temperature into the reactor during a time span of 2 h with simultaneously injecting into reaction mixture air with a rate of 12 to 14 l/h. The reaction mixture was stirred for another 6 h at 1000 rpm while air was further bubbled through the mixture. The organic phase was separated and washed three times with 30 ml of bi-distilled water (35 C.). A sample of this purified organic phase was determined by HPLC-w % to show a yield of 92,7% of quinone of formula C32.

CN12, EXAMPLE 985

Use of an Appropriate Amount of Catalyst, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0508] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were solubilized in 28,15 g of water and placed in the reactor. A solution of 134,6 g (312.51 mmol) of -tocopherol of formula C3 in 388,3 g of n-hexanol was added dropwise at 25 C. during 2 h. The mixture was further stirred for 5 h. During the whole reaction air at a rate of 40 l/h was bubbled through the reaction mixture and the reaction mixture while stirred at 1000 rpm. After termination of the reaction the aqueous phase was separated. A sample of the upper organic phase was taken and revealed a yield of 96% of -tocopherol quinone of formula C32 as determined by HPLC-w %.

CN13, EXAMPLE 988

Use of an Appropriate Amount of Catalyst, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0509] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were solubilized in 28,15 g of water and placed in the reactor together with 87,46 g of n-hexanol. A solution of 134,60 g (312.51 mmol) of -tocopherol of formula C3 in 298,86 g of n-hexanol was added dropwise at 25 C. during 2 h and the mixture was further stirred for 4,5 h. During the whole time air at a rate of 40 l/h was bubbled through the reaction mixture while stirring at 1000 rpm. After termination of the reaction the aqueous phase was separated. A sample of the upper organic phase was taken and revealed a yield of 97% of -tocopherol quinone of formula C32 as determined by HPLC.

CN14, EXAMPLE 905

Use of an Appropriate Amount of Catalyst, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0510] 13,32 g (78.1 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,2 g (1.6 mol) of water and placed in the reactor. 143,2 g (312.5 mmol) of -tocopherol of formula C5 were solubilized in 386,4 g (3.8 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 25 C. while bubbling 40 l/h of air through the mixture for 6 h. The aqueous phase was separated and the organic phase was washed three times with 170 ml water at 25 C. The solvent was removed at 100 C./8102 Pa and the product further degassed at 100 C./2102 Pa yielding 100% of quinone C33 as determined by HPLC-w %. By the methods indicated supra, the amount of organic chlorine was determined to be 77 ppm, the amount of chloride was determined to be 21 ppm and the amount of Cu ions was determined to be 13 ppm.

CN15, EXAMPLE 1052, CF. CN1

Use of an Appropriate Amount of Catalyst, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN16, EXAMPLE 1086

Use of an Appropriate Amount of Catalyst, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0511] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,15 g (1.56 mol) of water and placed in the reactor. 134,60 g (312.51 mmol) of -tocopherol of formula C5 were solubilized in 386,38 g (3.78 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 25 C. while bubbling 80 l/h of air through it for a period of 4 h. The aqueous phase was removed. The organic phase was washed three times with 170 ml water at 40 C. and a sample taken from the washed organic phase revealed a yield of 95% of quinone C33 as determined by HPLC-w %.

CN17, EXAMPLE 977

Use of an Appropriate Amount of Catalyst, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0512] 40,07 g (235.04 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were placed in the reactor and solubilized in 84.6 g of water. A solution of 101,23 g (235.03 mmol) of -tocopherol of formula C3 in 291,9 g of n-hexanol was added dropwise at 25 C. during a time span of 2 hours into the reactor while stirring at 1200 rpm and injecting air into the reaction mixture with a rate of 30 l/h. Stirring and air injection was continued for an additional hour after which a sample of the upper viz. organic phase was taken for HPLC analysis indicating a yield of 100% of quinone of the formula C32.

CN18, EXAMPLE 979

Use of an Appropriate Amount of Catalyst, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0513] 16,87 g (99.0 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 36,0 g (2.0 mol) of water and placed in the reactor. 83,0 g of n-hexanol were added to the reactor. 42,6 g (98.9 mmol) of rac--tocopherol C3 were dissolved in 39,9 g n-hexanol and added to the reactor within 4 h followed by 1 h of stirring (1200 rpm). Through the whole time the reaction mixture was maintained at 25 C. while bubbling 12-14 l/h of air through it. The aqueous phase was removed and the organic phase was washed three times with 54 ml water. The yield of quinone C32 in the organic phase was determined to be 95,5% by HPLC-w %.

CN19, EXAMPLE 977 CF. CN17

High Yield in Short Reaction Times, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN20, EXAMPLE 1052 CF. CN1

High Yield in Short Reaction Times, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN21, EXAMPLE 1021

High Yields in Short Reaction Times, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0514] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,15 g (1.56 mol) of water and placed in the reactor. 134,60 g (312.51 mmol) of -tocopherol of formula C5 were solubilized in 386,42 g (3.78 mol) of n-hexanol and added to the reactor. The reaction mixture was maintained at 25 C. with stirring at 1000 rpm while bubbling 40 l/h of air through it for a period of 4,75 h. A sample of the organic phase was taken and revealed 99% of -tocopherol quinone of formula C33 as determined by HPLC-w %.

CN22, EXAMPLE 1060

High Yields in Short Reaction Times, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0515] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,15 g (1.56 mol) of water and placed in the reactor. 134,60 g (312.51 mmol) of -tocopherol of formula C5 were solubilized in 386,36 g (3.78 mol) of n-hexanol and added into the reactor. The reaction mixture was maintained at 25 C. under stirring at 1000 rpm while bubbling 40 l/h of air through it for 4,75 h. The aqueous phase was removed. The organic phase was washed three times with water at 48 C. and the solvent removed at 90 C. at 2102 Pa. A sample of the residue was taken and revealed a yield of 100% of -tocopherol quinone of formula C33 as determined by HPLC-w %.

CN23, EXAMPLE 946

High Yields in Short Reaction Times, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0516] 4,22 g (24.6 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 and 10,06 g (49.48 mmol) of MgCl.sub.26 H.sub.2O were solubilized in 35.7 g of water and placed in the reactor. A solution of 42,6 g (98,93) mmol) of -tocopherol of formula C3 in 122,9 g of n-hexanol was also placed in the reactor. Thereafter air at a rate of 12 to 14 l/h was bubbled through the mixture while said mixture being stirred with air intake for 5 h at 23 C. After termination of the reaction the phases were separated and the organic phase was washed 3 times with 30 ml of water at 35 C. A sample of the organic phase was taken and revealed a yield of 94,9% of -tocopherol quinone of formula C32 as determined by HPLC-w %.

CN24, EXAMPLE 1054

High Yields in Short Reaction Times, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0517] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,15 g (1.56 mol) of water and placed in the reactor. 134,60 g (312.51 mmol) of -tocopherol of formula C5 were solubilized in 386,38 g (3.33 mol) of 3-heptanol and added to the reactor. The reaction mixture was maintained at 25 C. with stirring at 1000 rpm, while bubbling 40 l/h of air through it for a period of 5 h. The aqueous phase was removed. The organic phase was washed three times with 170 ml of water at 46 C. and the at least one solvent or the C-bearing solvent of the organic phase removed at 90 C. during 90 min under reduced pressure. A sample was taken and revealed a yield of 95,2% of -tocopherol quinone of formula C33 as determined by HPLC-w %. The amount of organic chlorine was analyzed by the methods indicated supra to be 60 ppm, the amount of chloride was 26 ppm and the amount of Cu was 12 ppm.

CN25, EXAMPLE 1032

High Yields in Short Reaction Times, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0518] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,15 g (1.56 mol) of water and placed in the reactor, which was thereafter supplemented with 87,5 g (856.42 mmol) of n-hexanol. The reaction mixture was maintained at 40 C. under stirring at 1000 rpm while bubbling 40l/h of air through it. 134,60 g (312.51 mmol) of -tocopherol of formula C5 were solubilized in 298,87 g (2.93 mol) of n-hexanol and added dropwise into the reactor during 4 h while stirring and bubbling. After a further hour of reaction, the aqueous phase was removed. The organic phase was washed three times with water and the solvent removed at 90 C. and 2102 Pa. A sample of the residue was taken and revealed a yield of 99% of -tocopherol quinone of formula C33 as determined by HPLC-w %. With the methods indicated supra, the amount of organic chlorine was determined to be 149 ppm, the amount of chloride to be 21 ppm and the amount of Cu ions to be 31 ppm.

CN26, EXAMPLE 877

High Yields in Short Reaction Times, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0519] 13,32 g (78.1 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,2 g (1.6 mol) of water and placed in the reactor. 143,2 g (312.5 mmol) of -tocopherol of formula C5 were solubilized in 386,4 g (3.8 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 15 C. while bubbling 40 l/h of air through the mixture for 6 h. The aqueous phase was separated, and the organic phase was washed three times with 170 ml water at 45-50 C. The solvent was removed at 100 C./1010.sup.2 Pa and the product further degassed at 100 C./110.sup.2 Pa yielding 99,1% of quinone C33 as determined by HPLC-w %. By the methods indicated supra, the amount of organic chlorine was determined to be 27 ppm, the amount of chloride was determined to be 9 ppm and the amount of Cu ions was determined to be 5 ppm.

CN27, EXAMPLE 905 CF. CN14

High Yields in Short Reaction Times, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN28, EXAMPLE 935

High Yields in Short Reaction Times, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0520] 5,8 g (25.9 mmol) of CuBr.sub.2, CAS no: 7789-45-9 were solubilized in 9.4 g of water and placed in the reactor together with 38,8 g of 2-ethyl-1-hexanol. A solution of 42,61 g (98.99 mmol) of -tocopherol of formula C3 in 90,6 g of 2-ethyl-1-hexanol was added dropwise at 50 C. during 2 h. The mixture was further stirred for 5 h at 50 C. During the whole reaction air at a rate of 12 to 14l/h was bubbled through the reaction mixture while stirring at 1000 rpm. After termination of the reaction, the phases were separated, and the organic phase was washed 3 times with 30 ml of bi-distilled water. A sample of the organic phase was taken and revealed 34% of -tocopherol quinone of formula C32 as determined by HPLC-w %.

CN29, EXAMPLE 942

High Yields in Short Reaction Times, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0521] 4,22 g (24.6 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 and 10,06 g (49.48 mmol) of MgCl.sub.26 H.sub.2O were solubilized in 35.7 g of water and placed in the reactor together with 34,6 g of n-hexanol. A solution of 42,6 g (98.93 mmol) of -tocopherol of formula C3 in 88,3 g of n-hexanol was added dropwise at 23 C. during 2 h followed by stirring for another 5 h. During the whole reaction air at a rate of 12 to 14 l/h was bubbled through the reaction mixture while stirring at 1000 rpm. After termination of the reaction, the phases were separated and the organic phase was washed 3 times with 30 ml of bi-distilled water (35 C.). A sample of the organic phase was taken and revealed a yield 97,5% of -tocopherol quinone of formula C32 as determined by HPLC-w %.

CN30, EXAMPLE 952 CF. CN11

High Yields in Short Reaction Times, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN31, EXAMPLE 976

High Yields in Short Reaction Times, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0522] 1,69 g (9.91 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were solubilized in 15 g of water and placed in the reactor. A solution of 42,6 g (98.93 mmol) of -tocopherol of formula C3 in 122,3 g of n-hexanol was likewise placed in the reactor. The reactor was warmed to 25 C. and air was bubbled through the reaction mixture at a rate of 12 to 14l/h for 10 h while stirring at 1200 rpm. 54 ml of bi-distilled water were added followed by stirring and phase separation. The organic phase was washed two times with 54 ml of bi-distilled water. A sample of the organic phase was taken and revealed a yield of 92,5% of -tocopherol quinone of formula C32 as determined by HPLC-w %.

CN32, EXAMPLE 941

Further Metal Compound in Addition to CuCl.SUB.2., Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0523] 4,2 g (24.64 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 and 4,19 g (98,85 mmol) of LiCl, CAS no: 7447-41-8 were dissolved in 35,65 g (1.98 mol) of water and placed in the reactor. 42,6 g (98.93 mmol) of -tocopherol of formula C3 were solubilized in 122,92 g (1.20 mol) of n-hexanol and added into the reactor. The reaction mixture was maintained at 25 C. under stirring at 1000 rpm while bubbling 12-14 l/h of air through it during 5 h. The aqueous phase was removed. The organic phase was washed three times with 30 ml of water. A sample of the organic phase was taken and revealed 94,6% of -tocopherol quinone of formula C32 as determined by HPLC-w %.

CN33, EXAMPLE 946 CF. CN23

Further Metal Compound in Addition to CuCl.SUB.2., Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN34, EXAMPLE 390

[0524] Amount of Metal Compound Used with Respect to Chroman C3, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0525] 4,02 g (23.58 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 and 3,99 g (94,13 mmol) of LiCl, CAS no: 7447-41-8 were dissolved in 84,65 g (4.69 mol) of water and placed in the reactor. 101,23 g (235.03 mmol) of -tocopherol of formula C3 were solubilized in 291,9 g (2.86 mol) of n-hexanol and added into the reactor during 2 h 15 min followed by stirring for 10,3 h. During the whole reaction the reaction mixture was maintained at 22 to 25 C. with stirring at 1000 rpm while bubbling 30 l/h of air through the reaction mixture. After addition of water and phase separation a sample of the organic phase revealed a yield of 87,2% of -tocopherol quinone of formula C32 as determined by HPLC-w %.

CN35, EXAMPLE 946, CF. CN23

[0526] Amount of Metal Compound Used with Respect to Chroman C3, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN36, EXAMPLE 952, CF. CN11

[0527] Amount of Metal Compound Used with Respect to Chroman C3, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN37, EXAMPLE 960

Concentration of Copper Catalyst in One of the at Least Two Solvents of the Solvent Mixture, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0528] 4,22 g (24.8 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 6,3 g (350.0 mmol) of water and placed in the reactor. 27,9 g (273.0 mmol) of n-hexanol were added to the reactor. 44,9 g (98.9 mmol) of -tocopherol of formula C3 were solubilized in 95,1 g (0.9 mol) of n-hexanol and added dropwise to the reactor over a period of 4 h followed by further stirring for 10 h. During the whole time the reaction mixture was stirred at 1000 rpm at 25 C. and 12-14 l/h of air were bubbled through the mixture. 54 ml of water were added to the reactor and the aqueous phase was separated. The organic phase was washed twice with 54 ml water yielding 87,2% of quinone C32 as determined in the organic phase by HPLC-w %.

CN38, EXAMPLE 974

Concentration of Copper Catalyst in One of the at Least Two Solvents of the Solvent Mixture, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0529] 3,37 g (19.8 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 33,0 g (1.8 mol) of water and placed in the reactor. 83,0 g (0.8 mol) of n-hexanol were added to the reactor. 44,9 g (98.9 mmol) of -tocopherol of formula C3 were solubilized in 39,9 g (0.4 mol) of n-hexanol and added dropwise to the reactor over a period of 4 h followed by further stirring for 5 h. During the whole time the reaction mixture was stirred at 1200 rpm at 25 C. and 12-14 l/h of air were bubbled through the mixture. The aqueous phase was separated, and the organic phase was washed three times with 54 ml water yielding 89,5% of quinone C32 as determined in the organic phase by HPLC-w %.

CN39, EXAMPLE 958

Concentration of Copper Catalyst in One of the at Least Two Solvents of the Solvent Mixture, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0530] 4,22 g (24.8 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 6,3 g (350.0 mmol) of water and placed in the reactor. 44,9 g (98.9 mmol) of -tocopherol of formula C3 were solubilized in 123,0 g (1.2 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 25 C. while bubbling 12-14 l/h of air through the mixture for 18 h. 54 ml of water were added, and the aqueous phase was separated. The organic phase was washed twice with 54 ml water yielding 91,8% of quinone C32 as determined by HPLC-w %.

CN40, EXAMPLE 952, CF. CN11

Concentration of Copper Catalyst in One of the at Least Two Solvents of the Solvent Mixture, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN41, EXAMPLE 971

Concentration of Copper Catalyst in One of the at Least Two Solvents of the Solvent Mixture, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0531] 3,37 g (19.8 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 8,0 g (444.4 mmol) of water and placed in the reactor. 83 g (0.81 mol) of n-hexanol were added to the reactor. 44,9 g (98.9 mmol) of -tocopherol of formula C3 were solubilized in 39,9 g (0.4 mol) of n-hexanol and added dropwise to the reactor over a period of 4 h followed by further stirring for 12 h. During the whole time the reaction mixture was stirred at 1200 rpm at 25 C. and 12-14 l/h of air were bubbled through the mixture. 54 ml of water were added to the reactor and the aqueous phase was separated. The organic phase was washed twice with 54 ml water yielding 93,5% of quinone C32 as determined by HPLC-w %.

CN42, EXAMPLE 872

Concentration of Chroman C1 in One of the at Least Two Solvents of the Solvent Mixture, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0532] 13,32 g (78.1 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,2 g (1.6 mol) of water and placed in the reactor. 142,6 g (312.5 mmol) of -tocopherol of formula C3 were solubilized in 285,2 g (2.8 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 25 C. while bubbling 40 l/h of air through the mixture for 5 h. The mixture was washed three times with 170 ml water at 45 C. yielding 97,5% of quinone C32 as determined in the organic phase by HPLC-w %.

CN43, EXAMPLE 1052, CF. CN1

Concentration of Chroman C1 in One of the at Least Two Solvents of the Solvent Mixture, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN44, EXAMPLE 875

Concentration of Chroman C1 in One of the at Least Two Solvents of the Solvent Mixture, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0533] 13,32 g (78.1 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,2 g (1.6 mol) of water and placed in the reactor. 142,6 g (312.5 mmol) of -tocopherol of formula C3 were solubilized in 142,6 g (1.4 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 25 C. while bubbling 40 l/h of air through the mixture for 5,5 h. The mixture was washed three times with 170 ml water at 45 C. water yielding 91,1% of quinone C32 as determined in the organic phase by HPLC-w %.

CN45, EXAMPLE 403

Weight Ratio of Organic Solvent to Water, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0534] 22,76 g (133.7 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 47,9 g (2.7 mol) of water and placed in the reactor. 57,2 g (89.5 mmol)R,R,R--tocopherol C5 were dissolved in 165,0 g n-hexanol and added to the reactor. The reaction mixture was maintained at 25 C. under stirring (750 rpm) while bubbling 30 l/h of air through it for 7 h. The phases were separated and the aqueous phase was removed. The organic phase was washed three times with 100 ml water and the solvent removed at 85 C./3,510.sup.2 Pa. A sample of the residue was taken and revealed a yield of 97,9% of -tocopherol quinone of formula C33 as determined by HPLC.

CN46, EXAMPLE 872, CF. CN42

Weight Ratio of Organic Solvent to Water, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN47, EXAMPLE 405

Weight Ratio of Organic Solvent to Water, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0535] 11,93 g (70.0 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 25,1 g (1.4 mol) of water and placed in the reactor. 30,0 g (46.5 mmol) of -tocopherol of formula C5 were solubilized in 173,0 g (1.7 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 850 rpm at 35-40 C. while bubbling 30 l/h of air through the mixture for 6 h. The aqueous phase was separated, the organic phase was washed three times with 100 ml water and the solvent was removed at 85 C. under reduced pressure yielding 96,2% of quinone C33 as determined by HPLC-w %.

CN48, EXAMPLE 941, CF. CN32

Weight Ratio of Organic Solvent to Water, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN49, EXAMPLE 1052, CF. CN1

Weight Ratio of Organic Solvent to Water, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN50, EXAMPLE 971, CF. CN41

Weight Ratio of Organic Solvent to Water, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN51, EXAMPLE 968, CF. CN10

Weight Ratio of Organic Solvent to Water, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN52, EXAMPLE 952, CF. CN11

Weight Ratio of Organic Solvent to Water, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN53, EXAMPLE 958, CF. 39

Weight Ratio of Organic Solvent to Water, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN54, EXAMPLE 875, CF. CN44

Weight Ratio of Organic Solvent to Water, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN55, EXAMPLE 974, CF. CN38

Weight Ratio of Organic Solvent to Water, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN56, EXAMPLE 390, CF. CN34

Weight Ratio of Organic Solvent to Water, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN57, EXAMPLE 960, CF. CN37

Weight Ratio of Organic Solvent to Water, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN58, EXAMPLE 905, CF. CN14

Short Reaction Time, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN59, EXAMPLE 1032, CF. CN25

Short Reaction Time, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN60, EXAMPLE 879

Short Reaction Time, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0536] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,15 g (1.56 mol) of water and placed in the reactor. 134,6 g (312.5 mmol) of -tocopherol of formula C5 were solubilized in 386,38 g (3.0 mol) of 2-octanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 25 C. while bubbling 80 l/h of air through the mixture for 6 h. The aqueous phase was separated, and the organic phase was washed three times with 170 ml water at 45 C. The solvent was removed at 130 C./1010.sup.2 Pa and the product further degassed at 130 C./1,310.sup.2 Pa yielding 98,8% of quinone C33 as determined by HPLC-w %. By the methods indicated supra, the amount of organic chlorine was determined to be 61 ppm, the amount of chloride was determined to be 9 ppm and the amount of Cu ions was determined to be 11 ppm.

CN61, EXAMPLE 1021, CF. CN21

Short Reaction Time, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN62, EXAMPLE 1074

Short Reaction Time, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0537] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,15 g (1.56 mol) of water and placed in the reactor. 134,60 g (312.51 mmol) of -tocopherol of formula C5 were solubilized in 386,38 g (3.33 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 25 C. while bubbling 40 l/h of air through it for a period of 6 h. The aqueous phase was removed. The organic phase was washed three times with 170 g bi-distilled water at 44-49 C. and a sample taken from the washed and slightly concentrated organic phase revealed a yield of 98% of quinone C33 as determined by HPLC-w %.

CN63, EXAMPLE 941, CF. CN32

Short Reaction Time, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN64, EXAMPLE 877, CF. CN26

Short Reaction Time, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN65, EXAMPLE 1054, CF. CN24

Short Reaction Time, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN66, EXAMPLE 1052, CF. CN1

Short Reaction Time, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN67, EXAMPLE 1086, CF. CN16

Short Reaction Time, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN68 EXAMPLE 1024

Moderate Temperature, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0538] 9,99 g (58.60 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 21,11 g (1.17 mol) of water and placed in the reactor. 100,95 g (234.38 mmol) of -tocopherol of formula C5 were solubilized in 289,77 g (2.84 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 10 C. while bubbling 30 l/h of air through it for a period of 9 h. The aqueous phase was removed. The organic phase was washed three times with 128 ml water at 40-45 C. and a sample taken from the washed organic phase revealed a yield of 93,6% of quinone C33 as determined by HPLC-w %. The at least one solvent or the C-bearing solvent of the organic phase mainly containing n-hexanol was removed during 45 min under reduced pressure at 90 C. By the methods indicated supra, the amount of organic chlorine was determined to be 100 ppm, the amount of chloride was determined to be 100 ppm and the amount of Cu ions was determined to be 105 ppm.

CN69, EXAMPLE 877, CF. CN26

Moderate Temperature, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN70, EXAMPLE 883

Moderate Temperature, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0539] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,15 g (1.56 mol) of water and placed in the reactor. 134,60 g (312.51 mmol) of -tocopherol of formula C5 were solubilized in 386,38 g (4.4 mol) of n-pentanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 15 C. while bubbling 40 l/h of air through it for a period of 7 h. The aqueous phase was separated, and the organic phase was washed three times with 170 ml of water at 20-41 C. The solvent was removed at 100 C./10102 Pa and the product further degassed at 100 C./2,4102 Pa yielding 93,4% of quinone C33 as determined by HPLC-w %. By the methods indicated supra, the amount of organic chlorine was determined to be 30 ppm, the amount of chloride was determined to be 480 ppm and the amount of Cu ions was determined to be 630 ppm.

CN71, EXAMPLE 941, CF. CN32

Moderate Temperature, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN72, EXAMPLE 942, CF. CN29

Moderate Temperature, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN73, EXAMPLE 1060, CF. CN22

Moderate Temperature, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN74, EXAMPLE 905, CF. CN14

Moderate Temperature, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN75, EXAMPLE 988, CF. CN13

Moderate Temperature, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C32

CN76, EXAMPLE 894

Moderate Temperature, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0540] 13,32 g (78.1 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,2 g (1.6 mol) of water and placed in the reactor. 143,2 g (312.5 mmol) of -tocopherol of formula C5 were solubilized in 386,4 g (4.4 mol) of n-pentanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 25 C. while bubbling 40 l/h of air through the mixture for 8 h. The aqueous phase was separated, and the organic phase was washed three times with 170 ml water at 25 C. The solvent was removed at 100 C./1010.sup.2 Pa and the product further degassed at 100 C./210.sup.2 Pa yielding 94,0% of quinone C33 as determined by HPLC-w %.

CN77, EXAMPLE 1054, CF. CN24

Moderate Temperature, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN78, EXAMPLE 879, CF. CN60

Moderate Temperature, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN79, EXAMPLE 994

Moderate Temperature, Batchwise Synthesis of -Tocopherol Quinone of Formula C32

[0541] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 was dissolved in 28,15 g (1.56 mol) of water and placed in the reactor. 134,60 g (312.51 mmol) of -tocopherol of formula C3 were solubilized in 386,32 g (3.78 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 25 C. while bubbling 40 l/h of air through it for a period of 7 h. The aqueous phase was removed, and the organic phase was washed three times with water. The at least one solvent or the C-bearing solvent of the organic phase was removed under reduced pressure at 80 C. yielding 145,3 g corresponding to a yield of 92,1% as determined by. The product was degassed at 110 C. and 2,3102 Pa and the amount of organic chlorine was determined to be 126 ppm, the amount of chloride 14 ppm and the amount of Cu was 49 ppm.

CN80, EXAMPLE 1032, CF. CN25

Moderate Temperature, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN81, EXAMPLE 1042

Influence of Reaction Temperature and Reaction Time on Formation of Reagent Traces and Side-Product Traces, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0542] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,15 g (1.56 mol) of water and placed in the reactor, which was thereafter supplemented with 87,5 g (856.42 mmol) of n-hexanol. The reaction mixture was maintained at 25 C. under stirring at 1000 rpm while bubbling 40l/h of air through it. 134,60 g (312.51 mmol) of -tocopherol of formula C5 were solubilized in 298,87 g (2.93 mol) of n-hexanol and added dropwise into the reactor during 4 h while stirring and bubbling. After a further two hours of reaction, the aqueous phase was removed. The organic phase was washed three times with 170 ml of water at 40-47 C. Removal of solvent from the organic Phase yielded 98,6% of -tocopherol quinone of formula C33 as determined by HPLC-w %. By the methods indicated supra, the amount of organic chlorine was determined to be 88 ppm, the amount of chloride was determined to be 12 ppm and the amount of Cu ions was determined to be 8 ppm.

CN82, EXAMPLE 1032, CF. CN25

Influence of Reaction Temperature and Reaction Time on Formation of Reagent Traces and Side-Product Traces, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0543] This example per se is an inventive example, however, serves as comparison with respect to reaction temperature and reaction time on the aforementioned trace-formation.

CN83, EXAMPLE 1036

Influence of Reaction Temperature and Reaction Time on Formation of Reagent Traces and Side-Product Traces, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0544] This example per se is an inventive example, however, serves as comparison with respect to reaction temperature and reaction time on the aforementioned trace-formation.

[0545] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,15 g (1.56 mol) of water and placed in the reactor, which was thereafter supplemented with 87,5 g (671.89 mmol) of 2-ethylhexanol. The reaction mixture was maintained at 55 C. under stirring at 1000 rpm while bubbling 40 l/h of air through it. 134,60 g (312.51 mmol) of -tocopherol of formula C5 were solubilized in 298,72 g (2.29 mol) of 2-ethylhexanol and added dropwise into the reactor during 4 h while stirring and bubbling. After a further hour of reaction, the aqueous phase was removed. The organic phase was washed three times with 170 ml of water at 48 C. A sample of the combined organic phases was taken and revealed 98% of -tocopherol quinone of formula C33 as determined by HPLC. The solvent was removed from the organic phase, and by the methods indicated supra, the amount of organic chlorine was determined to be 356 ppm, the amount of chloride was determined to be 34 ppm and the amount of Cu ions was determined to be 40 ppm.

CN84, EXAMPLE 886

Influence of Reaction Temperature and Reaction Time on Formation of Reagent Traces and Side-Product Traces, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0546] 13,32 g (78.1 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,2 g (1.6 mol) of water and placed in the reactor. 143,2 g (312.5 mmol) of -tocopherol of formula C5 were solubilized in 386,4 g (3.8 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 10 C. while bubbling 40 l/h of air through the mixture for 8 h. The mixture was washed three times with 170 ml water at 45-50 C. and the solvent removed at 100 C./1010.sup.2 Pa. The product was further degassed at 100 C./110.sup.2 Pa yielding 95,6% of -tocopherol quinone C33 as determined by HPLC-w %. By the methods indicated supra, the amount of organic chlorine was determined to be 70 ppm, the amount of chloride was determined to be 80 ppm and the amount of Cu ions was determined to be 95 ppm.

CN85, EXAMPLE 877, CF. CN26

Influence of Reaction Temperature and Reaction Time on Formation of Reagent Traces and Side-Product Traces, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN86, EXAMPLE 883, CF. CN70

Influence of Reaction Temperature and Reaction Time on Formation of Reagent Traces and Side-Product Traces, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN87, EXAMPLE 1080

Influence of Reaction Temperature and Reaction Time on Formation of Reagent Traces and Side-Product Traces, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0547] 13,32 g (78.1 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,2 g (1.6 mol) of water and placed in the reactor. 144,2 g (312.5 mmol) of -tocopherol of formula C5 were solubilized in 386,4 g (3.8 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 25 C. while bubbling 40 l/h of air through the mixture for 4,75 h. The aqueous phase was separated, and the organic phase was washed three times with 170 ml water at 47-49 C. The solvent was removed at 100 C./1010.sup.2 Pa and the product further degassed at 100 C./110.sup.2 Pa yielding 94,5% of quinone C33 as determined by HPLC-w %. By the methods indicated supra, the amount of organic chlorine was determined to be 44 ppm, the amount of chloride was determined to be 32 ppm and the amount of Cu ions was determined to be 30 ppm.

CN88, EXAMPLE 905, CF. CN14

Influence of Reaction Temperature and Reaction Time on Formation of Reagent Traces and Side-Product Traces, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN89, EXAMPLE 1054, CF. CN24

Influence of Reaction Temperature and Reaction Time on Formation of Reagent Traces and Side-Product Traces, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN90, EXAMPLE 879, CF. CN60

Influence of Reaction Temperature and Reaction Time on Formation of Reagent Traces and Side-Product Traces, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

CN91, EXAMPLE 1024, CF. CN68

Influence of Reaction Temperature and Reaction Time on Formation of Reagent Traces and Side-Product Traces, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0548] This example per se is an inventive example, however, serves as comparison with respect to reaction temperature and reaction time on the aforementioned trace-formation.

CN92, EXAMPLE 1040

Influence of Reaction Temperature and Reaction Time on Formation of Reagent Traces and Side-Product Traces, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0549] This example per se is an inventive example, however, serves as comparison with respect to reaction temperature and reaction time on the aforementioned trace-formation.

[0550] 13,32 g (78.13 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,15 g (1.56 mol) of water and placed in the reactor. 134,60 g (312.51 mmol) of -tocopherol of formula C5 were solubilized in 386,42 g (3.78 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 25 C. while bubbling 40 l/h of air through it for a period of 23 h. The aqueous phase was removed. The organic phase was washed three times with water and the at least one solvent or the C-bearing solvent of the organic phase removed at 90 C. during 45 min under reduced pressure. A sample was taken and revealed a yield of 96% of quinone C33 as determined by HPLC-w %. By the methods indicated supra, the amount of organic chlorine was determined to be 293 ppm, the amount of chloride was determined to be 27 ppm and the amount of Cu ions was determined to be 23 ppm.

CN93, EXAMPLE 1010

Influence of Reaction Temperature and Reaction Time on Formation of Reagent Traces and Side-Product Traces, Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0551] This example per se is an inventive example, however, serves as comparison with respect to reaction temperature and reaction time on the aforementioned trace-formation.

[0552] 13,32 g (78.1 mmol) of CuCl.sub.22 H.sub.2O, CAS no: 10125-13-0 were dissolved in 28,2 g (1.6 mol) of water and placed in the reactor. 144,2 g (312.5 mmol) of -tocopherol of formula C5 were solubilized in 386,4 g (3.8 mol) of n-hexanol and added to the reactor. The reaction mixture was stirred at 1000 rpm at 40 C. while bubbling 40 l/h of air through the mixture for 5 h. The aqueous phase was separated, and the organic phase washed three times with 170 ml water at 40 C. The solvent was removed at 90 C./210.sup.2 Pa yielding 148,9 g, 88,8 t % of -tocopherol quinone of formula C33 as determined by HPLC-w %. By the methods indicated supra, the amount of organic chlorine was determined to be 250 ppm, the amount of chloride was determined to be 70 ppm and the amount of Cu ions was determined to be 100 ppm.

CN94, EXAMPLE 1044 WITH SAMPLE FROM EXAMPLE 1042

Influence of the Separation Means on Formation of Reagent Traces and Side-Product Traces, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0553] A G3 glass suction filter (volume of 1 l, 12.5 cm inner diameter) was filled with a slurry of 355 g of silica (particle size 40 to 63 m) in n-heptane to a height of 6.7 cm giving a volume of 822 ml. 35,5 g of -tocopherol quinone of formula C33 of example 1042 (cf. CN81) were dissolved in 35,5 g of n-heptane and applied onto the wet silica. Under suction another 1000 ml of n-heptane were added. Thereafter elution was realized two times with 2.428 g of a solution of n-heptane comprising 3 w % of isopropyl acetate yielding fractions 1 and 2 followed by one elution with 2.428 g of a solution of n-heptane containing 20 w % of isopropyl acetate yielding fraction 3. Said fraction 3 was freed from solvent and dried to give 34,1 g of -tocopherol quinone of formula C33 (quinone preparation of the invention). The amount of organic chlorine in said quinone preparation was 16 ppm, the amount of chloride <3 ppm and the amount of Cu was <3 ppm

CN95, EXAMPLE 1033 WITH SAMPLE FROM EXAMPLE 1032

Influence of the Separation Means on Formation of Reagent Traces and Side-Product Traces, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0554] A G3 glass suction filter (volume of 1 l, 12.5 cm inner diameter) was filled with a slurry of 355 g silica (particle size 40 to 63 m) in n-heptane to a height of 6.7 cm giving a volume of 822 ml. 35,5 g of -tocopherol quinone of formula C33 of example 1032 (cf. CN25) were dissolved in 35,5 g of n-heptane and applied onto the wet silica. Under suction another 1000 ml of n-heptane were added. Thereafter elution was realized two times with 2.428 g of a solution of n-heptane comprising 3 w % of isopropyl acetate yielding fractions 1 and 2 followed by one elution with 2.428 g of a solution of n-heptane containing 20 w % of isopropyl acetate yielding fraction 3. Said fraction 3 was freed from solvent and dried to give 34,1 g of -tocopherol quinone of formula C33 quinone preparation of the invention. The amount of organic chlorine in said quinone preparation was 76 ppm, the amount of chloride <3 ppm and the amount of Cu was <3 ppm.

CN96, EXAMPLE 1038 WITH SAMPLE FROM EXAMPLE 1036

Influence of the Separation Means on Formation of Reagent Traces and Side-Product Traces, Semi-Batchwise Synthesis of -Tocopherol Quinone of Formula C33

[0555] A G3 glass suction filter (volume of 1 l, 12.5 cm inner diameter) was filled with a slurry of 355 g silica (particle size 40 to 63 m) in n-heptane to a height of 6.7 cm giving a volume of 822 ml. 35,5 g of -tocopherol quinone of formula C33 of example 1036 (cf. CN83) were dissolved in 35,5 g of n-heptane and applied onto the wet silica. Under suction another 1000 ml of n-heptane were added. Thereafter elution was realized two times with 2.428 g of a solution of n-heptane comprising 3 w % of isopropyl acetate yielding fractions 1 and 2 followed by one elution with 2.428 g of a solution of n-heptane containing 20 w % of isopropyl acetate yielding fraction 3. Said fraction 3 was freed from solvent and dried to give 30,0 g of -tocopherol quinone of formula C33 (quinone preparation of the invention). The amount of organic chlorine in said quinone preparation was 210 ppm, the amount of chloride <3 ppm and the amount of Cu was <3 ppm.

CN97, EXAMPLE 895 WITH SAMPLE FROM EXAMPLE 886