ACIDIC ELIMINATION FOR BIO-BASED AROMATICS

Abstract

A process for the preparation of an aromatic product is disclosed which includes a step b) of contacting one or more intermediate compounds with a further acid to form the aromatic product. The intermediate compounds can be obtained in step a) that includes contacting a 7-oxabicyclo[2.2.1]hept-2-ene core structure with an acidic mixture. The amount of acid in step b) is higher than the amount of acid in step a).

Claims

1. A process for the preparation of an aromatic product according to formula IIIa or IIIb, said process comprising a step a) of contacting a cycloadduct according to formula I with an acidic mixture comprising a first acid and optionally an activating agent to obtain one or more intermediate compounds, which is followed by a step b) of contacting one or more intermediate compounds with a further acid, which further acid is more of the first acid and/or an additional acid with respect to the first acid of step a) to form the aromatic product according to formula IIIa or IIIb, ##STR00015## wherein, R.sub.1 and/or R.sub.2 are independently selected from the group consisting of H, C.sub.1-C.sub.20 alkyl, CHO and hydrazones, oximes, hemiacetals and acetals thereof, CH.sub.2OH and esters and ethers thereof, CO.sub.2H and esters thereof, and amides and tertiary amines of CH.sub.2NH.sub.2 and optionally polymer-supported; R.sub.3 and/or R.sub.4 are independently selected from the group consisting of H, CH.sub.3, acetals, hemiacetal, hydrazones and oximes of CHO, CH.sub.2OH and esters and ethers thereof, CO.sub.2H and esters thereof, amides and tertiary amines of CH.sub.2NH.sub.2, and one or more electron-withdrawing groups, or R.sub.3 and R.sub.4 together represent —(CO)X(CO)—, wherein X═O, CH.sub.2, NH, NMe, NEt, NPr, NBu, NPh, or S; or R.sub.2 and R.sub.4 together represent —CH.sub.2ZC(O)—, wherein Z is selected from the group consisting of O, NH and S; and represents a single or double bond.

2. The process according to claim 1, wherein the intermediate compounds in step b) are present in a mixture including part of the acidic mixture.

3. The process according to claim 1, wherein the further acid is a dry acid.

4. The process according to claim 1, wherein the amount of further acid that is contacted with the one or more intermediate compounds is at least 0.25 molar equivalents.

5. The process according to claim 1, wherein step a) is carried out at a temperature below 100° C.

6. The process according to claim 1, wherein step b) further comprises heating the intermediate compounds to a temperature of more than 30° C.

7. The process according to claim 1, wherein the acid mixture comprises an activating agent selected from the group consisting of acylating agents, triflating agents, sulfonating agents, carbamylating agents, carbonylating agents, or combinations thereof.

8. The process according to claim 7, wherein the activation agent and cycloadduct are contacted in a molar range of 30:1 to 1:1.

9. The process according to claim 1, wherein the first acid and cycloadduct are contacted in a molar range of at least 0.01:1.

10. The process according to claim 1, wherein the first acid comprises an acid selected from the group consisting of organic acids, dry inorganic acids and solid acids.

11. The process according to claim 1, wherein the first acid and the further acid comprise the same type of acid.

12. The process according to claim 1, wherein steps a) and b) are continuous processes.

13. The process according to claim 1, wherein said process comprises removing at least part of unreacted activating agent.

14. The process according to claim 1, wherein step b) is followed by isolating the aromatic product by cooling or evaporative crystallization.

15. The process in accordance with claim 1, wherein said process further comprises the step of hydrolyzing the aromatic product to obtain a phthalic acid.

16. The process of claim 15, wherein said phthalic acid is according to any of formulae IVa-IVc, ##STR00016##

17. The process of claim 4, wherein, wherein the amount of further acid that is contacted with the one or more intermediate compounds is at 2 equivalents based on the starting amount of the cycloadduct.

18. The process of claim 5, wherein step a) is carried out at a temperature in the range of 10 to 60° C. and wherein step b) further comprises heating the intermediate compounds to a temperature in the range of 40° C. to 150° C.

19. The process of claim 9, wherein the first acid and cycloadduct are contacted in a molar range of 1:1 to 0.1:1.

20. The process of claim 1, wherein the one or more electron-withdrawing groups are selected from the group consisting of CF.sub.3, CCl.sub.3, CBr.sub.3, CI.sub.3, NO.sub.2, CN, SO.sub.2Q, SO.sub.3Q, COQ, COF, COCl, COBr, COI, CO.sub.2Q, C(O)NQ, and C(═NT)Q, wherein Q and T are independently H, or linear or branched C.sub.1-C.sub.8-alkyl, optionally substituted with halogens and optionally polymer-supported.

21. The process of claim 1, wherein R.sub.3 and R.sub.4 together represent —(CO)O(CO)—, —(CO)NMe(CO)—, —(CO)NEt(CO)— or —(CO)NPr(CO).

22. The process of claim 1, wherein R.sub.1 and R.sub.2 both are H or methyl, or R.sub.1 is hydrogen and R.sub.2 is methyl.

Description

EXAMPLE 1: PRODUCTION OF 3-MPA USING SULFURIC ACID

[0079] A mixture of acetic anhydride (3.048 mL, 4 equivalents) with sulfolane as an internal standard (0.211 mL, 0.2 equivalent) was prepared and cooled to 0° C. To this solution, sulfuric acid (0.308 mL, 0.5 equivalents) was added dropwise. The solution was kept at 0° C. and the Diels-Alder adduct of 2-methylfuran and maleic anhydride (2.0 g, 1 equivalent) was slowly added (over roughly 30 minutes), keeping the temperature beneath 10° C. The mixture was left to stir until a precipitate was visible, then the reaction mixture was heated up to 60° C. At the moment the precipitate dissolved into solution, the reaction mixture was split up in 5 reaction tubes (Tubes A to E).). Tubes A-E contained respectively 0, 0.64, 1.28, 1.93 and 2.57 equivalent of sulfuric acid (relative to the Diels-Alder adduct of 2-methylfuran and maleic anhydride) before the reaction solution was added. This point was taken as t=0.

[0080] Reactions were analysed by NMR after 30, 70, 120, 180, 240 and 300 minutes at 60° C. Sampling was done by taking 45 μL of reaction mixture diluting in 550 μL CDCl3.

[0081] Results are provided in FIG. 1 which displays the formed amount of 3-methylphthalic anhydride (3-MPA) with different sulfuric acid concentrations. Further, based on the amounts of formed 3-MPA, residual intermediate and amount of maleic anhydride, the mass balances of tubes A-E were found to be respectively, 87.50%, 84.45%, 83.59%, 83.84% and 86.45%.

[0082] Based on these results, it can be concluded that the addition of 0.6 equivalents further sulfuric acid to the reaction has a significant effect on the reaction time—which could be decreased from 6 to ˜2 hours. If 2.6 equivalents further acid is added, the reaction can already be stopped after ±30 minutes, with 1.5% intermediate remaining. This decreases the reaction time from 6 hours to <1 hour.

EXAMPLE 2: PRODUCTION OF 3-MPA USING SULFURIC ACID AND AMBERLYST-15

[0083] A mixture of acetic anhydride (3.048 mL, 4 equivalents) with sulfolane as an internal standard (0.211 mL, 0.2 equivalent) was prepared and cooled to 0° C. To this solution, sulfuric acid (0.308 mL, 0.5 equivalents) was added dropwise. The solution was kept at 0° C. and the Diels-Alder adduct of 2-methylfuran and maleic anhydride (2.0 g, 1 equivalent) was added slowly (over roughly 30 minutes), keeping the temperature beneath 10° C. The mixture was left to stir until a precipitate was visible, then the mixture was heated up to 60° C. At the moment the precipitate dissolved into solution, the reaction mixture was split up in 5 reaction tubes (Tubes A to E). Tubes A-E contained respectively 0, 50, 100, 200 and 400 mg of Amberlyst-15 resin before the reaction solution was added. This point was taken as t=0.

[0084] Reactions were analysed by NMR after 60, 120, 180, 240 and 300 minutes at 60° C. Sampling was done by taking 45 μL of reaction mixture diluting in 550 μL CDCl3.

[0085] Results are provided in FIG. 2 which displays the formed amount of 3-methylphthalic anhydride (3-MPA) with different sulfuric acid concentrations. Further, based on the amounts of formed 3-MPA, residual intermediate and amount of maleic anhydride, the mass balances of tubes A-E were found to be respectively, 87.4%, 89.0%, 91.6%, 93.1% and 96.8%.

[0086] Based on these results, it can be concluded that addition of Amberlyst-15 to the reaction has a significant effect on the conversion in time, as well as the selectivity to 3-MPA. The strongest effects are observed at high Amberlyst-15 loading, with the conversion after 5 hours being 7% higher, and the yield on 3-MPA 16% higher. This corresponds to a more selective reaction, with lower by-product formation, which is clearly shown by the improved mass balance. A slight reduction in processing time can also be achieved by this approach.

EXAMPLE 3: PRODUCTION OF 3-MPA USING SULFURIC ACID AND TRIFLUOROACETIC ACID

[0087] A mixture of acetic anhydride (3.048 mL, 4 equivalents) with sulfolane as an internal standard (0.211 mL, 0.2 equivalent) was prepared and cooled to 0° C. To this solution, sulfuric acid (0.308 mL, 0.5 equivalents) was added dropwise. The solution was kept at 0° C. and the Diels-Alder adduct of 2-methylfuran and maleic anhydride (2.0 g, 1 equivalent) was slowly added (over roughly 30 minutes), keeping the temperature beneath 10° C. The mixture was left to stir until a precipitate was visible, then the reaction mixture was heated up to 60° C. At the moment the precipitate dissolved into solution, the reaction mixture was split up in 5 reaction tubes (Tubes A to E).). Tubes A-E contained respectively 0, 0.64, 1.28, 1.93 and 2.57 equivalent of trifluoroacetic acid (relative to the Diels-Alder adduct of 2-methylfuran and maleic anhydride) before the reaction solution was added. This point was taken as t=0.

[0088] Reactions were analysed by NMR after 30 and 90 minutes at 60° C. Sampling was performed by taking 45 μL of reaction mixture diluting in 550 μL CDCl3.

[0089] Results are provided in FIG. 3 which displays the formed amount of 3-methylphthalic anhydride (3-MPA) with different trifluoroacetic acid concentrations. Based on these results, it can be concluded that the addition of a small amount of trifluoracetic acid already significantly reduces the time required for conversion to 3-methylphthalic anhydride, and increasing the levels of trifluoroacetic acid further increases the rate of reaction, with almost complete conversion achieved after 90 minutes with 2.57 eq. of trifluoroacetic acid.

EXAMPLE 4: PRODUCTION OF 3-MPA USING SULFURIC ACID AND TRIFLUOROMETHANESULFONIC ACID

[0090] A mixture of acetic anhydride (3.048 mL, 4 equivalents) with sulfolane as an internal standard (0.211 mL, 0.2 equivalent) was prepared and cooled to 0° C. To this solution, sulfuric acid (0.308 mL, 0.5 equivalents) was added dropwise. The solution was kept at 0° C. and the Diels-Alder adduct of 2-methylfuran and maleic anhydride (2.0 g, 1 equivalent) was slowly added (over roughly 30 minutes), keeping the temperature beneath 10° C. The mixture was left to stir until a precipitate was visible, then the reaction mixture was heated up to 60° C. At the moment the precipitate dissolved into solution, the reaction mixture was split up in 5 reaction tubes (Tubes A to E).). Tubes A-E contained respectively 0, 0.64, 1.28, 1.93 and 2.57 equivalent of trifluoromethanesulfonic acid (relative to the Diels-Alder adduct of 2-methylfuran and maleic anhydride) before the reaction solution was added. This point was taken as t=0.

[0091] Reactions were analysed by NMR after 30 and 90 minutes at 60° C. Sampling was performed by taking 45 μL of reaction mixture diluting in 550 μL CDCl3.

[0092] Results are provided in FIG. 4 which displays the formed amount of 3-methylphthalic anhydride (3-MPA) with different trifluoromethanesulfonic acid concentrations. Based on these results, it can be concluded that the addition of even a small amount of trifluoromethanesulfonic acid already significantly reduces the time required for conversion to 3-methylphthalic anhydride so that (almost) complete conversion has taken place within 30 minutes at all concentrations.

EXAMPLE 5: PRODUCTION OF 3-MPA USING SULFURIC ACID AND NAFION-NR50

[0093] A mixture of acetic anhydride (3.048 mL, 4 equivalents) with sulfolane as an internal standard (0.211 mL, 0.2 equivalent) was prepared and cooled to 0° C. To this solution, sulfuric acid (0.308 mL, 0.5 equivalents) was added dropwise. The solution was kept at 0° C. and the Diels-Alder adduct of 2-methylfuran and maleic anhydride (2.0 g, 1 equivalent) was slowly added (over roughly 30 minutes), keeping the temperature beneath 10° C. The mixture was left to stir until a precipitate was visible, then the reaction mixture was heated up to 60° C. At the moment the precipitate dissolved into solution, the reaction mixture was split up in 5 reaction tubes (Tubes A to E).). Tubes A-E contained respectively 0, 50, 100, 200 and 400 mg of Nafion-NR50 resin before the reaction solution was added. This point was taken as t=0.

[0094] Reactions were analysed by NMR after 30, 90, 120, 180 minutes at 60° C. Sampling was performed by taking 45 μL of reaction mixture diluting in 550 μL CDCl3.

[0095] Results are provided in FIG. 5 which displays the formed amount of 3-methylphthalic anhydride (3-MPA) with different Nafion-NR50 loadings. Based on these results, it can be concluded that the addition of Nafion-NR50 has a small effect on the rate of reaction, with slightly higher yield of 3-methylphthalic anhydride achieved in the same time period when compared to the control reaction. Without wishing to be bound by theory, the difference between the results with

[0096] Amberlyst-15 is believed to be due to the loading. The Nafion beads used in the present invention are approximately 20-50 times larger than the Amberlyst beads, so the relative acidic loading is very low. A mild acceleration with Amberlyst-15 (compared to no extra acid being added) is observed while the main advantage is in the selectivity (see Examples 1 and 2). Likely, increasing the acid loading of the Nafion beads further will give a significant rate increase while yielding the selectivity observed with Amberlyst-15.

EXAMPLE 6: PRODUCTION OF 3-MPA USING SULFURIC ACID AND AMBERLYST-36

[0097] A mixture of acetic anhydride (3.048 mL, 4 equivalents) with sulfolane as an internal standard (0.211 mL, 0.2 equivalent) was prepared and cooled to 0° C. To this solution, sulfuric acid (0.308 mL, 0.5 equivalents) was added dropwise. The solution was kept at 0° C. and the Diels-Alder adduct of 2-methylfuran and maleic anhydride (2.0 g, 1 equivalent) was slowly added (over roughly 30 minutes), keeping the temperature beneath 10° C. The mixture was left to stir until a precipitate was visible, then the reaction mixture was heated up to 60° C. At the moment the precipitate dissolved into solution, the reaction mixture was split up in 5 reaction tubes (Tubes A to E).). Tubes A-E contained respectively 0, 50, 100, 200 and 400 mg of Amberlyst-36 resin before the reaction solution was added. This point was taken as t=0.

[0098] Reactions were analysed by NMR after 30, 90, and 120 minutes at 60° C. Sampling was performed by taking 45 μL of reaction mixture diluting in 550 μL CDCl3.

[0099] Results are provided in FIG. 6 which displays the formed amount of 3-methylphthalic anhydride (3-MPA) with different Amberlyst-36 loadings. Based on the results, it can be concluded that the addition of Amberlyst-36 has a small positive effect on the rate of reaction to 3-methylphthalic anhydride, but at higher loadings and longer reaction times hydrolysis of the product anhydride by water present in the resin results in poor selectivity from 3-methylphthalic anhydride. It was observed that the combined formation of 3-methylphthalic anhydride and of its hydrolysed product increased with the amount of Amberlyst-36 being present, which is a clear indication of a rate enhancement.

EXAMPLE 7: PRODUCTION OF 3-MPA USING SULFURIC ACID AND AMBERLYST-15

[0100] In a 1 L reactor, mixture of acetic anhydride (570 ml) and sulfuric acid (42 ml) was cooled to 0° C., then the Diels-Alder adduct formed between 2-methylfuran and maleic anhydride (272 g) was added over a period of 60 minutes, maintaining an internal temperature of less than 10° C. To the mixture was added Amberlyst-15 resin (40.85 g) and the mixture was heated to 60° C. and held for 6 hours. The mixture was then cooled to 0° C. and the formed solid was then isolated by filtration. The isolated product was then washed with acetic acid (100 ml). After drying, this yielded a mixture of 3-methylphthalic anhydride and Amberlyst-15 as an off-white solid with black resin present (190.15 g total=149.3 g 3-methylphthalic anhydride, 61.0%). The filtrates of the reaction were then analysed by NMR against an internal standard (dimethyl maleate) which showed a further 89.8 g of 3-methylphthalic anhydride to be present (36.7%). The selectivity to 3-methylphathalic anhydride was therefore 97.7%.

COMPARATIVE EXAMPLE 1: PRODUCTION OF 3-MPA USING SULFURIC ACID

[0101] In a 1 L reactor, mixture of acetic anhydride (571 ml) and sulfuric acid (42 ml) was cooled to 0° C., then the Diels-Alder adduct formed between 2-methylfuran and maleic anhydride (271 g) was added over a period of 60 minutes, maintaining an internal temperature of less than 10° C. The mixture was then heated to 60° C. and held for 6 hours. The mixture was then cooled to 0° C. and the formed solid was then isolated by filtration. The isolated product was then washed with acetic acid (100 ml). After drying, this yielded 3-methylphthalic anhydride as an off-white solid (111.4 g, 45.7%). The filtrates of the reaction were then analysed by NMR against an internal standard (dimethyl maleate) which showed a further 91.2 g of 3-methylphthalic anhydride to be present (37.4%). The selectivity to 3-methylphathalic anhydride was therefore 83.1%.