Method for preparing phenolics using a catalyst

Abstract

The invention is directed to a method for preparing a phenolic compound comprising reacting a furanic compound with a dienophile in the presence of a catalyst comprising yttrium.

Claims

1. Method for preparing a phenolic compound comprising reacting a furanic compound with a dienophile in the presence of a catalyst comprising yttrium.

2. Method according to claim 1, wherein the catalyst further comprises a ligand.

3. Method according to claim 1, wherein the catalyst comprises yttrium(III) triflate.

4. Method according to claim 1, wherein the catalyst is applied on a solid support.

5. Method according to claim 1 wherein the furanic compound is a compound according to formula I ##STR00010## wherein R.sub.1 and R.sub.2 are independently selected from the group consisting of H, linear or branched C.sub.1-C.sub.8 alkyl, F, Cl, Br, I, CH.sub.2F, CH.sub.2Cl, CH.sub.2Br, CH.sub.2I, CN, NO.sub.2, CHO, CO.sub.2H or esters thereof, CH.sub.2NH.sub.2 or secondary amines, tertiary amines, quaternary amines or amides thereof, and CH.sub.2OH or esters or ethers thereof; and wherein the furanic compound is optionally bound to a solid support.

6. Method according to claim 1 wherein the dienophile is acetylene, optionally substituted with one or more linear or branched C.sub.1-C.sub.8 alkyl groups, or wherein the dienophile is a compound according to formula (II) ##STR00011## wherein EWG is an electron withdrawing group and R.sub.3H, linear or branched C.sub.1-C.sub.8 alkyl.

7. Method according to claim 1, wherein the phenolic compound is one or more phenolic compound selected from the group consisting of compounds according to the following formulae IIIa-IIIh: ##STR00012##

8. Method according to claim 1, wherein reacting the furanic compound with the dienophile is carried out in an apolar, aprotic and/or non-coordinating solvent.

9. Method according to claim 1, wherein reacting the furanic compound with the dienophile is carried out at a temperature ranging from 60-350 C.

10. Method according to claim 1, wherein the phenolic compound is reacted further in one or more reaction steps selected from the group consisting of hydrolysis, oxidation, reduction, nucleophilic addition, olefination, rearrangement, decarboxylation, and decarbonylation to obtain a final phenolic product.

11. Method according to claim 10, wherein the final phenolic product is selected from the group consisting of phenol, o-alkylphenol, m-alkylphenol, p-alkylphenol, cresols, o-hydroxybenzoic acid, m-hydroxybenzoic acid, p-hydroxybenzoic acid, 2,6-dialkylphenol, 2,5-dialkylphenol, 2,4-dialkylphenol, 2,3-dialkylphenol, 3,4-dialkylphenol, 3,5-dialkylphenol, xylenols, 2,3,4-trialkylphenol, 2,3,5-trialkylphenol, 2,3,6-trialkylphenol, 2,4,5-trialkylphenol, 2,4,6-trialkylphenol, 3,4,5-trialkylphenol, o-nitrophenol, m-nitrophenol, p-nitrophenol, o-cyanophenol, m-cyanophenol, p-cyanophenol, catechol, resorcinol, hydroquione, o-halophenol, m-halophenol, p-halophenol, o-aminophenol, m-aminophenol, p-aminophenol, o-hydroxystyrene, m-hydroxystyrene, p-hydroxystyrene, o-hydroxybenzyl alcohol, m-hydroxybenzyl alcohol, p-hydroxybenzyl alcohol, o-hydroxybenzyl amine, m-hydroxybenzyl amine, p-hydroxybenzyl amine, o-hydroxyacetophenone, m-hydroxyacetophenone, p-hydroxyacetophenone, o-hydroxybenzaldehyde, m-hydroxybenzaldehyde, p-hydroxybenzaldehyde, o-hydroxybenzamide, m-hydroxybenzamide, p-hydroxybenzamide and combinations thereof.

12. Method according to claim 2, wherein the ligand is a sulfonate ligand.

13. Method according to claim 12, wherein the sulfonate ligand comprises an alkyl group, an aryl group, or an electron-withdrawing group.

14. Method according to claim 13, wherein the electron-withdrawing group is a halogenated group comprising at least one halogen atom, a perhalogenated group, a perfluoroalkyl, or a trifluoromethyl group.

15. Method according to claim 4, wherein the solid support comprises a polymeric support, silica, alumina, silica-alumina, or a zeolite.

16. Method according to claim 6, wherein EWG is I, CN, NO.sub.2, CO.sub.2X, C(O)NX, C(NY)X, CF.sub.3, CCl.sub.3, CBr.sub.3, CI.sub.3, SO.sub.2X, SO.sub.3X, COH, COX, COF, COCl, COBr, or COI, wherein X and Y are independently H, or linear or branched C.sub.1-C.sub.8 alkyl, optionally substituted with halogens and optionally polymer-supported.

17. Method according to claim 8, wherein the solvent is a C.sub.4-C.sub.12 hydrocarbon, ether, esters, toluene, heptane, or mesitylene.

18. Method according to claim 9, wherein the temperature ranges from 20-180 C.

Description

EXAMPLES

Example 1

(1) A catalyst (about 0.09 mmol, 0.1 equivalent) was weighed into a reactor and dissolved in toluene (0.5 mL). Methyl propiolate (MP) (80.1 L, 1 equivalent) was added to the mixture, then 2-methylfuran (2-MF) (85.2 L, 1.05 equivalent) was added. The reaction mixture was stirred for 2 h at 140 C. The product (2-methyl-5-hydroxymethylbenzoate, MHMB) was obtained by evaporation, addition of dichloromethane, washing with water, drying and filtration. The yield was determined by HPLC.

(2) Table 1 shows as comparative result that AlCl.sub.13 and aluminium(III) trifluoromethanesulfonate (Al(OTf).sub.3) as catalyst provided a yield of 0-3%, except for THF which provided 19% yield (with 48% 2-MF remaining)

(3) TABLE-US-00001 TABLE 1 Comparative examples Catalyst Mol % catalyst Solvent T ( C.)/t Yield AlCl.sub.3 12% THF 140/2 H 19% AlCl.sub.3 8% Toluene RT/16 H 2% AlCl.sub.3 12% MeCN 140/2 H 0% AlCl.sub.3 17% MeOH 140/2 H 0% AlCl.sub.3 17% EtOAc 140/2 H 3% Al(OTf).sub.3 9% THF 140/2 H 2% Al(OTf).sub.3 9% Toluene 140/2 H 2% Al(OTf).sub.3 11% MeCN 80/2 H 1% Al(OTf).sub.3 13% MeOH 80/2 H 1% Al(OTf).sub.3 14% EtOAc 80/2 H 0%

(4) Surprisingly high yields were obtained with yttrium(III) trifluoromethanesulfonate (Y(OTf).sub.3) as catalyst, as shown in Table 2.

(5) TABLE-US-00002 TABLE 2 Eq. Catalyst catalyst Solvent T ( C.)/t Yield Y(OTf).sub.3 6% THF 140/2 H 34% Y(OTf).sub.3 10% Toluene 140/2 H 78% Y(OTf).sub.3 9% MeCN 140/2 H 46% Y(OTf).sub.3 8% MeOH 140/2 H 6% Y(OTf).sub.3 73% EtOAc 140/2 H 37%

(6) For Y(OTf).sub.3 as catalyst, a yield of 76% was obtained with heptane and a yield of 78% with mesitylene as solvent (using the same procedure).

Example 2

(7) A supported catalyst was prepared by washing Amberlyst 15 resin in a column with methanol and water and a saturated Na.sub.2SO.sub.4 solution until the eluent in neutral, washing with water and drying to give the Na.sup.+ exchanged resin. The resin (2 g) was contacted with the catalyst Y(OTf).sub.3 (2 mmol) and ethanol (5 mL) for 16 hours, then the solvent was filtered off, the resin washed thoroughly, and then dried. The reaction of 2-MF and MP was performed with this catalyst at 120 C. After about 45 hour the yield was about 30%.

Example 3

(8) An experiment as in Example 1 was performed, but the 2-MF (1.05 eq.) was added continuously over 180 minutes to a solution of 2.86 mol/L MP in toluene, with Y(OTf).sub.3 (0.05 eq.) as catalyst, at 150 C., provided a 79% yield of MHMB.

Example 4

(9) ##STR00008##

(10) Yttrium triflate (0.11 mmol, 0.01 equivalent) was weighed into a reactor and dissolved in toluene (6.5 mL). Methyl propiolate (MP) (960 L, 1 equivalent) was added to the mixture, then furan (809 L, 1.1 equivalent) was added. The reaction mixture was heated to 140 C. and stirred for 6 h. The reaction mixture was cooled to room temperature then washed with saturated sodium bicarbonate solution, then water. The organics were dried over sodium sulfate, filtered and reduced to an oil. This was purified by column chromatography to methyl 2-hydroxybenzoate (27% yield) and methyl 2-hydroxybenzoate (31% yield).

Example 5

(11) ##STR00009##

(12) Yttrium triflate (0.11 mmol, 0.01 equivalent) was weighed into a reactor and dissolved in toluene (6.5 mL). Methyl propiolate (MP) (960 L, 1 equivalent) was added to the mixture, then 2,5-dimethylfuran (1282 L, 1.1 equivalent) was added. The reaction mixture was heated to 140 C. and stirred for 2 h. The reaction mixture was cooled to room temperature then washed with saturated sodium bicarbonate solution, then water. The organics were dried over sodium sulfate, filtered and reduced to an oil. This was purified by column chromatography to 4 separate regioisomers of the desired product (Combined yield=83%).

Example 6

(13) A supported catalyst was prepared by washing Amberlyst 15 resin in a column with methanol and water and a saturated Na.sub.2SO.sub.4 solution until the eluent in neutral, washing with water and drying to give the Na.sup.+ exchanged resin. The resin (2 g) was contacted with the catalyst Y(OTf).sub.3 (2 mmol) and ethanol (5 mL) for 16 hours, then the solvent was filtered off, the resin washed thoroughly, and then dried. The reaction of 2,5-dimethylfuran and methyl propiolate was performed at 120 C. using this catalyst. After 16 hours, reaction mixture was cooled to room temperature then filtered to remove the catalyst, and the filtrate was washed with water. The organics were dried over sodium sulfate, filtered and reduced to an oil. This was purified by column chromatography yield the same 4 products as were isolated in the reaction with the non-supported catalyst (Combined yield=77%).