WO2007042114A1

WO2007042114A1 - Process for the oxidation of organic substrates by means of singlet oxygen at high reaction temperatures

Info

Publication number: WO2007042114A1
Application number: PCT/EP2006/008906
Authority: WO
Inventors: Walther Jary; Eduard Perndofer; Martin Lassnig
Original assignee: Dsm Fine Chemicals Austria Nfg Gmbh & Co Kg
Priority date: 2005-10-13
Filing date: 2006-09-13
Publication date: 2007-04-19
Also published as: AT502537B1; AT502537A1

Abstract

Process for the oxidation of organic substrates by means of singlet oxygen, in which organic substrates which react with 1O2 are admixed with 10-70% strength H2O2 in an organic solvent in the presence of a molybdenum-based catalyst at a pH of 9 - 14 and a temperature in the range from 500C to the reflux temperature, whereupon the oxidation to the corresponding oxidation products occurs subsequent to the catalytic decomposition of H2O2 into water and 1O2.

Description

Process for the oxidation of organic substrates by means of singlet oxygen at high reaction temperatures

The invention relates to a process for the oxidation of organic substrates by means of singlet oxygen at high reaction temperatures.

The only singlet oxygen oxidation (¹θ₂-Ox) which is at present carried out industrially is the photochemical ¹O₂-Ox, in which the ¹O₂ is generated photochemically. The disadvantages of this process are the high costs of the photochemical facilities required and a restricted life. The lamps required degenerate relatively quickly during the oxidation as a result of fouling of the glass surface. In addition, this process is not suitable for colored substrates. The process is actually suitable only for fine chemicals which are prepared on a relatively small scale. (La Chimica e I'lndustria, 1982, Vol. 64, page 156) For this reason, attempts have been made to find other process variants for ¹O₂-Ox which are suitable for the ¹O₂-Ox of hydrophobic organic substrates which are not soluble in water.

J. Am. Chem. Soc, 1968, 90, 975, describes, for example, the classical "dark" ¹O₂-Ox in which ¹O₂ is not generated photochemically but instead is generated chemically. Here, hydrophobic substrates are oxidized by means of a hypochlorite/H₂O₂ system in a solvent mixture comprising water and an organic solvent. However, this process has found only a few synthetic applications, since many substrates are only sparingly soluble in the medium required. The opportunities for use are also fairly restricted because of secondary reactions between hypochlorite and substrate or solvent. In addition, a large part of the ¹O₂ is deactivated in the gas phase. Furthermore, this process is not suitable for an industrial scale since an addition reaction of hypochlorite with H₂O₂ occurs in the organic medium and a large excess of H₂O₂ is required to suppress the secondary reaction of substrate with hypochlorite. An additional disadvantage is the formation of stoichiometric amounts of salts.

One variant of "dark" ¹θ₂-Ox which is not based on hypochlorite and should thus avoid part of the above disadvantages is known, for example, from J. Org. Chem., 1989, 54, 726 or J. MoI. Cat., 1997, 117, 439, according to which certain water-soluble organic substrates are oxidized by means of H₂O₂ and a molybdate catalyst in water as solvent. According to Membrane Lipid Oxid. Vol. II, 1991, 65, the ¹θ₂-Ox of water-insoluble, organic substrates by means of the molybdate/H2θ₂ system is difficult, because it was assumed that none of the customary solvents is able to maintain the molybdate-catalyzed disproportionation of H₂O₂ in water and ¹θ₂. However, the use of molybdenum catalysts is also associated with other disadvantages such as difficult recyclability or environmental pollution.

The use of molybdate-LDH catalysts for singlet oxygen oxidation is known from various literature references, for example from Adv. Synth. Catal. 2004, 346, 152-164, Chem. Commun., 1998, 267, or Chem. Eur. J. 2001, 7, 2547, but these do not have satisfactory selectivity and do not give satisfactory yields. EP 1 169 281 discloses the singlet oxygen oxidation of organic substances in an organic solvent in the presence of a homogeneous catalyst based on molybdenum at from 0 to 50⁰C.

A further possible way of generating ¹θ₂ chemically is, for example, heating of triphenyl phosphite ozonide which is obtained from triphenyl phosphite and ozone. However, this method as described, for instance, in J. Org. Chem., Vol. 67, No 8, 2002, page 2418, can be employed only for mechanistic studies since triphenyl phosphite is an expensive and also hazardous chemical. The base-catalyzed disproportionation of peracids forms not only ¹O₂ but also further reactive compounds which lead to by-products. It was accordingly an object of the present invention to make the oxidation of organic substrates by means of singlet oxygen (¹O₂) possible while avoiding accumulation of hydrogen peroxide in the reaction mixture and avoiding molybdenum-containing wastewater and also to discover a catalytic system for this purpose which has a high activity and selectivity.

This object has unexpectedly been able to be realised when the reaction is carried out at high reaction temperatures.

The present invention accordingly provides a process for the oxidation of organic substrates by means of singlet oxygen, wherein organic substrates which react with ¹O₂ are admixed with 10-70% strength H₂O₂ in an organic solvent in the presence of a molybdenum-based catalyst at a pH of 9 - 14 and a temperature in the range from 50⁰C to the reflux temperature, whereupon the oxidation to the corresponding oxidation products occurs subsequent to the catalytic decomposition of H₂O₂ into water and ¹O₂.

In the process of the invention, organic substrates are oxidized by means of singlet oxygen.

As organic substrates which react with ¹O₂, it is possible to use the following compounds: olefins which have one or more, i.e. up to 10, preferably up to 6, particularly preferably up to 4, C=C double bonds; electron-rich aromatics such as C₆-C₅₀-, preferably up to C₃₀-, particularly preferably up to C₂₀-phenols, polyalkylbenzenes, polyalkoxybenzenes; polycyclic aromatics having from 2 to 10, preferably up to 6, particularly preferably up to 4, aromatic rings; sulfides such as alkyl sulfides, alkenyl sulfides, aryl sulfides which are either monosubstituted or disubstituted on the sulfur atom and heterocycles having an O, N or S atom in the ring, for example C4-C50-, preferably up to C30-, particularly preferably up to C₂o-furans, C₄-C_5O-, preferably up to C30-. particularly preferably up to C₂₀-pyrroles, C₄-C_6O-, preferably up to C30-. particularly preferably up to C₂o-thiophenes, C₄-C₆o-. preferably up to C₃₀-, particularly preferably up to C₂o-indoles.

The substrates can have one or more substituents such as halogen (F, Cl, Br, I), cyanide, carbonyl groups, hydroxyl groups, C1-C50-, preferably up to C30-, particularly preferably up to C₂o-alkoxy groups, C₁-C5₀-, preferably up to C30-, particularly preferably up to C₂₀-alkyl groups, C₆-C₅₀-, preferably up to C30-, particularly preferably up to C₂₀-aryl groups, C₂-C₅₀-, preferably up to C30-, particularly preferably up to C₂₀-alkenyl groups, C₂-C₅₀-, preferably up to C30-, particularly preferably up to C₂o-alkynyl groups, carboxylic acid groups, ester groups, amide groups, amino groups, nitro groups, silyl groups, silyloxy groups, sulfone groups, sulfoxide groups, etc. Furthermore, the substrates can be substituted by one or more NR1 R2 radicals, where R1 and R2 can be identical or different and are each H; Ci-C₅₀-, preferably up to C₃₀-, particularly preferably up to C₂o-alkyl; formyl; C₂-C₅₀-, preferably up to C30-, particularly preferably up to C₂₀-acyl; C₇-C₅₀-, preferably up to C₃₀-, particularly preferably up to C₂o-benzoyl; where R1 and R2 can together also form a ring, e.g. in a phthalimido group.

Examples of suitable substrates are: 2-butene; isobutene; 2-methyl-1-butene; 2-hexene; 1 ,3-butadiene; 2,3-dimethylbutene; D⁹ⁱ¹⁰-octalin, 2-phthalimido-4- methyl-3-pentene; 2,3-dimethyl-1 ,3-butadiene; 2,4-hexadiene; 2-chloro-4- methyl-3-pentene; 2-bromo-4-methyl-3-pentene; 1 -trimethylsilylcyclohexene; 2,3-dimethyl-2-butenyl-para-tolyl sulfone; 2,3-dimethyl-2-butenyl-para-tolyl sulfoxide; Λ/-cyclohexenylmorpholine; 2-methyl-2-norbornene; terpinols; α- pinene; β-pinene; β-citronellol; ocimene; citronellol; geraniol; farnesol; terpinene; limonene; fra/7S-2,3-dimethylacrylic acid; α-teφinene; isoprene; cyclopentadiene; 1 ,4-diphenylbutadiene; 2-ethoxybutadiene; 1 ,1'- dicyclohexenyl; cholesterol; ergosterol acetate; 5-chloro-1 ,3-cyclohexadiene; 3- methyl-2-buten-1-ol; 3,5,5-trimethylcyclohex-2-en-1-ol; phenol, 1 ,2,4- trimethoxybenzene, 2,3,6-trimethylphenol, 2,4,6-trimethylphenol, 1 ,4- dimethylnaphthalene, furan, furfuryl alcohol, furfural, 2,5-dimethylfuran, isobenzofuran, 2,3-dimethylindole, dibenzyl sulfide, (2-methyl-5-ferf- butyl)phenyl sulfide, etc.

The substrates are converted into the corresponding oxidation product by means of the oxidation according to the invention. Alkenes, (polycyclic) aromatics or heteroaromatics are converted, in particular, into hydroperoxides or peroxides which can react further under the reaction conditions to form alcohols, epoxides, acetals or carbonyl compounds such as ketones, aldehydes, carboxylic acids or esters if the hydroperoxide or the peroxide is not stable.

The oxidation according to the invention is carried out in an organic solvent. Suitable solvents are CrC₈-alcohols such as methanol, ethanol, propanol, i- propanol, butanol, i-butanol, n-butanol, tert-butanol, ethylene glycol, propylene glycol, acetone, 1 ,4-dioxane, tetrahydrofuran, formamide, N-methylformamide, dimethylformamide, sulfolane, propylene carbonate and mixtures thereof. Preference is given to using methanol, ethanol, propanol, i-propanol, ethylene glycol, propylene glycol, acetone, formamide, N-methylformamide or dimethylformamide, particularly preferably methanol, ethanol, ethylene glycol, propylene glycol, formamide or dimethylformamide, as solvent. If desired, up to 25% of water can be mixed into the organic solvent. However, the addition of water gives no advantages in the reaction. Preference is therefore given to no water being added.

The appropriate substrate is taken up or dissolved in the solvent selected. A molybdenum-based catalyst is then added to the solvent/substrate mixture. The catalyst can here be used in the forms customary for ¹θ2 oxidations, for example as oxide, oxo complex, nitrate, carboxylate, hydroxide, carbonate, chloride, etc., or as molybdate-LDH catalyst.

The amount of catalyst used depends on the substrate used and is in the range from 0.001 to 50 mol%, preferably from 0.1 to 10 mol%.

If appropriate, a base is added to the reaction mixture so that a pH of from 9 to

14, preferably from 10 to 13, is set.

Suitable bases are customary bases such as NaOH, KOH, etc.

10-70% strength, preferably 40-50% strength, H₂O₂ is subsequently added.

The consumption of H₂O₂ in the process of the invention is dependent on the substrate used. In the case of reactive substrates, from 2 to 3 equivalents of

H₂O₂ are preferably required, while less reactive substrates are preferably reacted with from 3 to 10 equivalents of H₂O₂.

The reaction temperature is in the range from 50⁰C to reflux temperature, preferably from 55⁰C to reflux temperature.

The higher the reaction temperature, the more quickly can the H₂O₂ be added, so that the reaction time can be significantly minimized.

The course of the reaction can be followed by means of UV spectroscopy, GC,

DC, GC-MS or by means of HPLC.

After the reaction is complete, the reaction mixture is worked up.

The work-up of the reaction solution containing the oxidation product is carried out, if appropriate after reduction of the peroxides, by customary methods such as extraction, drying and isolation of the oxidation product.

The catalyst can, particularly when glycols are used as solvents, be recycled in a simple manner and be reused a number of times. This can be carried out in a simple fashion by, after isolating the product, distilling off water from the remaining solution which contains the catalyst and reusing the resulting catalyst solution directly for a fresh reaction.

The process of the invention is particularly useful for the oxidation of substituted or unsubstituted 2,3-dimethylindole to prepare 2-(N-acetylamino)acetophenone. This variant for preparing 2-(N-acetylamino)acetophenone is novel and is therefore also provided by the present invention.

¹O₂ is generated in a simple and efficient way by means of the process of the invention.

The process of the invention gives the desired end products in high yields of up to 100% and high purity.

The process of the invention is simple to carry out and is best suited for the industrial scale since it can be carried out in simple multipurpose plants and with the aid of simple work-up steps and can be employed for a broad spectrum of substrates. A further advantage is the multiple reusability of the molybdenum catalyst used.

Example 1 :

40.0 g of beta-citronellol were taken up in 240 ml of methanol and placed in a 500 ml double-walled vessel. 3.1 g of sodium molybdate were dissolved in 23.2 g of water and added to the solution, and the pH was then adjusted to pH=11.7 by means of sodium hydroxide.

The mixture was heated to 55°C and 2.9 equivalents of hydrogen peroxide (50% strength) were then metered in over a period of 6 hours.

After reduction of the peroxides, the reaction mixture was analyzed by gas chromatography. Conversion: >95% based on citronellol used.

Product: (1 :1 mixture of: 3,7-dimethyloct-7-ene-1 ,6-diol and 3,7-dimethyloct-5- ene-1 ,7-diol)

Example 2:

240.0 g of beta-citronellol were taken up in 1500 ml of ethylene glycol and 16.7 g of sodium molybdate and 30 g of water were added. (pH = 10.3). The solution was placed in a double-walled vessel and heated to 55°C. 313.1 g of hydrogen peroxide were added over a period of 6 hours (43.5 ml/h). After the reaction was complete, the reaction mixture was introduced into a sodium sulfite solution (193.5 g of sodium sulfite in 550 ml of water) and the peroxide solution was reduced at 60⁰C. The sodium sulfate was filtered off and the solution was extracted with MTBE (4 times with 500 ml each time). The MTBE extracts were then evaporated.

Yield: 266 g (1 :1 mixture of: 3,7-dimethyloct-7-ene-1 ,6-diol and 3,7-dimethyloct- 5-ene-1,7-diol)

Example 3

10.9 g of 2,3-dimethylindole were dissolved in 250 ml of ethylene glycol. 0.9 g of sodium molybdate and 1.5 g of water were added. The mixture was then heated to 50⁰C. 5.2 equivalents of hydrogen peroxide were metered in over a period of 17 hours. The peroxide-containing solution was reduced by means of sodium sulfite/water, the precipitated sodium sulfate was filtered off and the reaction mixture was extracted with MTBE (twice with 150 ml each time). The combined organic extracts were then evaporated. The residue was taken up in 30 ml of methanol and the product was crystallized out at O⁰C. This gave 2-(N-acetylamino)acetophenone having a purity of 97.5%.

Example 4:

240.0 g of beta-citronellol were taken up in 1500 ml of ethylene glycol and 16.7 g of sodium molybdate and 30 g of water were added. (pH = 10.3). The solution was placed in a double-walled vessel and heated to 70⁰C. 313.1 g of hydrogen peroxide were added over a period of 6 hours (43.5 ml/h). After the reaction was complete, the reaction mixture was introduced into a sodium sulfite solution (193.5 g of sodium sulfite in 550 ml of water) and the peroxide solution was reduced at 60⁰C. The sodium sulfate was filtered off and the solution was extracted with MTBE (4 times with 500 ml each time). The MTBE extracts were then evaporated.

Example 5:

10.9 g of 2,3-dimethylindole were dissolved in 250 ml of ethylene glycol. 0.9 g of sodium molybdate and 1.5 g of water were added. The mixture was then heated to 70°C. 5.2 equivalents of hydrogen peroxide were metered in over a period of 17 hours. The peroxide-containing solution was reduced by means of sodium sulfite/water, the precipitated sodium sulfate was filtered off and the reaction mixture was extracted with MTBE (twice with 150 ml each time). The combined organic extracts were then evaporated. The residue was taken up in 30 ml of methanol and the product was crystallized out at 0⁰C.

This gave 2-(N-acetylamino)acetophenone having a purity of 97.5%. Example 6:

1.6 g of citronellol were taken up in 9.6 ml of methanol and placed in a 20 ml double-walled vessel. 0.124 g of sodium molybdate was dissolved in 0.93 g of water and added. The pH was set to pH = 11.7 by means of 0.02 g of 5% strength NaOH and the solution was brought to reflux temperature (72°C methanol/water). 2.9 equivalents of 50% strength hydrogen peroxide were then added over a period of 30 minutes.

Analysis of the mixture after reduction of the peroxides indicated complete conversion (1 :1 mixture of: 3,7-dimethyloct-7-ene-1 ,6-diol and 3,7-dimethyloct- 5-ene-1 ,7-diol)

Example 7:

1.6 g of citronellol were taken up in 9.6 ml of methanol and placed in a 20 ml double-walled vessel. 0.124 g of sodium molybdate was dissolved in 0.93 g of water and added. The pH was set to pH = 11.7 by means of 0.02 g of 5% strength NaOH and the solution was brought to reflux temperature (73°C methanol/water). 2.9 equivalents of 50% strength hydrogen peroxide were then added all at once. After 5 minutes, the reaction mixture was reduced.

Analysis of the mixture after reduction of the peroxides indicated complete conversion (1 :1 mixture of: 3,7-dimethyloct-7-ene-1 ,6-diol and 3,7-dimethyloct- 5-ene-1 ,7-diol) Example 8: Trial with recycling of glycol catalyst solution

240.0 g of beta-citronellol were taken up in 1500 ml of ethylene glycol and 16.7 g of sodium molybdate and 30 g of water were added. (pH = 10.3). The solution was placed in a double-walled vessel and heated to 70⁰C. 313.1 g of hydrogen peroxide were added over a period of 6 hours (43.5 ml/h). After the reaction was complete, the reaction mixture was introduced into a sodium sulfite solution (193.5 g of sodium sulfite in 550 ml of water) and the peroxide solution was reduced at 6O⁰C. The sodium sulfate was filtered off and the solution was extracted with MTBE (4 times with 500 ml each time). The MTBE extracts were then evaporated.

Yield: 266 g (1 :1 mixture of: 3,7-dimethyloct-7-ene-1 ,6-diol and 3,7-dimethyloct- 5-ene-1 ,7-diol)

Recycling of the glycol phase with catalyst

The water was removed from the glycol/water phase by means of distillation or using a membrane.

240.0 g of beta-citronellol were added to the remaining 1556 g of ethylene glycol/catalyst/water. The yellow-orange solution was heated to 55⁰C and 313 g of hydrogen peroxide were added (43.5 ml/min). After the reaction was complete, the reaction mixture was introduced into a sodium sulfite solution (193.5 g of sodium sulfite in 550 ml of water) and the peroxide solution was reduced at 60°C. The sodium sulfate was filtered off and the solution was extracted with MTBE (4 times with 500 ml each time). The MTBE extracts were then evaporated.

Yield: 258 g (1 :1 mixture of: 3,7-dimethyloct-7-ene-1 ,6-diol and 3,7-dimethyloct- 5-ene-1 ,7-diol) The glycol/water/cataiyst phase could be processed as described above and reused.

Claims

Claims:

1. A process for the oxidation of organic substrates by means of singlet oxygen, wherein organic substrates which react with ¹θ₂ are admixed with 10-70% strength H₂O₂ in an organic solvent in the presence of a molybdenum-based catalyst at a pH of 9 - 14 and a temperature in the range from 5O⁰C to the reflux temperature, whereupon the oxidation to the corresponding oxidation products occurs subsequent to the catalytic decomposition of H₂O₂ into water and ¹O₂.

2. The process as claimed in claim 1 , wherein olefins containing from 1 to 10 C=C double bonds; Cβ-Csrj-phenols, polyalkylbenzenes; polyalkoxybenzenes; polycyclic aromatics having from 2 to 10 aromatic rings; alkyl sulfides, alkenyl sulfides, aryl sulfides which are either monosubstituted or disubstituted on the sulfur atom and also C^Cβfj-heterocycles which have an O₁ N or S atom in the ring and may be unsubstituted or monosubstituted or multiply substituted by halogens, cyanide, carbonyl groups, hydroxy! groups, C<|-C5o-alkoxy groups, C-|-C5o-alkyl groups, Cβ-Csrj-acryl groups,

C2-C5Q-alkenyl groups, C2-C5Q-alkynyl groups, carboxylic acid groups, ester groups, amide groups, amino groups, nitro groups, silyl groups, silyloxy groups, sulfone groups, sulfoxide groups or one or more NR^ R^ radicals, where R-| and R2 can be identical or different and are each H; C<|-C5rj-alkyl; formyl; C2-C5fj-acyl; C7-C5o-benzoyl, where R1 and R2 can together also form a ring, are used as substrates which react with ¹O₂.

3. The process as claimed in claim 1 , wherein C-i-Cs-alcohols, acetone, 1 ,4- dioxane, tetrahydrofuran, formamide, N-methylformamide, dimethylformamide, sulfolane, propylene carbonate or a mixture thereof is used as solvent.

4. The process as claimed in claim 3, wherein methanol, ethanol, propanol, i- propanol, ethylene glycol, propylene glycol, acetone, formamide, N- methylformamide or dimethylformamide is used as solvent.

5. The process as claimed in claim 1 , wherein, depending on the substrate, from 0.001 to 50 mol% of catalyst are used.

6. The process as claimed in claim 1 , wherein, depending on the substrate used, from 2 to 10 equivalents of H₂O₂ are used.

7. The process as claimed in claim 1 , wherein the reaction temperature is in the range from 55°C to reflux temperature.

8. The process as claimed in claim 1 , wherein, after the corresponding oxidation products have been isolated from the reaction mixture, water is removed from the catalyst-containing solution which remains and the catalyst/solvent mixture obtained in this way is used for further oxidations.

9. A process for the oxidation of substituted or unsubstituted 2,3-dimethylindole, wherein the substituted or unsubstituted 2,3-dimethylindole is admixed with 10-70% strength H₂O₂ in an organic solvent in the presence of a molybdenum-based catalyst at a pH of 9 - 14 and a temperature in the range from 50⁰C to the reflux temperature, whereupon the oxidation to substituted or unsubstituted 2-(N-acetylamino)acetophenone occurs subsequent to the catalytic decomposition of H₂O₂ into water and ¹O₂.