NEW PROCESS FOR PREPARING BIPHENYL COMPOUNDS

Abstract

The present invention relates to a process for preparing a compound having the formula (I), said process comprising the following steps: a) the addition of an oxygen source into a solution of a compound of formula (II), in a water-miscible solvent, b) the addition of a laccase in the solution obtained after step a); and c) the possible recovering of the compound of formula (I) thus obtained.

##STR00001##

Claims

1. A process for preparing a compound having the formula (I): ##STR00056## wherein: R.sub.1 is H or OH; R.sub.2 is a (C.sub.1-C.sub.6)alkoxy group; R.sub.3 is H or forms a C═O group with the carbon atom carrying it; R.sub.4 is R or R’; R being chosen from the group consisting of: —CHO, —CN, —COR.sub.a, —COOR.sub.a, —R.sub.a, and (C.sub.2-C.sub.6)alkenyl groups, R.sub.a being a (C.sub.1-C.sub.6)alkyl group; R′ being a (C.sub.1-C.sub.6)alkoxy group; and wherein, when the bond ‘a’ linking the cores A and B is a single bond, then the compound of formula (I) has the following formula (I-1): ##STR00057## and when the bond ‘a’ linking the cores A and B is a double bond, then the compound of formula (I) has the following formula (I-2): ##STR00058## said process comprising the following steps: a) the addition of an oxygen source into a solution of a compound of formula (II) in a water-miscible solvent, said compound of formula (II) having the following formula: ##STR00059## wherein R.sub.1, R.sub.2, and R.sub.4 are as defined above in formula (I), and R′.sub.3 is H when R.sub.1 is OH and R′.sub.3 is OH when R.sub.1 is H, said water-miscible solvent being chosen from the group consisting of: dioxane, DMSO, acetone, and mixtures thereof; b) the addition of a laccase in the solution obtained after step a); and c) the recovering of the compound of formula (I) thus obtained, in particular by centrifugation or filtration.

2. The process of claim 1, wherein the water-miscible solvent is acetone.

3. The process of claim 1 or 2, wherein the laccase is from Trametes versicolor.

4. The process of claim 1, wherein the amount of laccase for one gram of compound of formula (II) is from 1.5 mg to 75 mg, preferably from 3 mg to 15 mg.

5. The process of claim 1, wherein the solution of the compound of formula (II) in a water-miscible solvent is prepared by adding said compound of formula (II) in said water-miscible solvent, and adding a buffer solution.

6. The process according to claim 5, wherein the amount of water-miscible solvent is comprised between 5% and 10% of volume in comparison with the total volume of the mixture formed by said solvent and the buffer solution.

7. The process of claim 1, wherein the addition of an oxygen source according to step a) is carried out for a sufficient time to saturate the solution in dissolved oxygen.

8. The process of claim 1, wherein the solution of the compound of formula (II) in the water-miscible solvent used for step b) is saturated in oxygen.

9. The process of claim 1, wherein the pH of the solution of the compound of formula (II) in the water-miscible solvent is comprised between 4 and 7.

10. A process for the preparation of a compound having the following formula (III): ##STR00060## R and R.sub.2 being as defined in claim 1, and R.sub.5 being a (C.sub.1-C.sub.6)alkyl group; said process comprising the steps of: preparing a compound of formula (I-1 ) using the process according to claim 1, alkylating the compound of formula (IA) with a compound R.sub.5X, X being a halogen atom, preferably I, and the possible recovering of the compound of formula (III).

11. The process of claim 10, wherein R is —CHO, —CH.sub.2—CH═CH.sub.2 or COOR.sub.a, R.sub.a being a (C.sub.1-C.sub.6)alkyl group.

12. A process for the preparation of a compound having the following formula (IV): ##STR00061## R.sub.2 being as defined in claim 1, and R.sub.6 being H or a (C.sub.1-C.sub.6)alkyl group, said process comprising the steps of: preparing a compound of formula (I-1) with R being CHO, using the process claim 1, reacting the compound of formula (I-1) with a hydrogenation agent, in order to obtain a compound of formula (IV) wherein R.sub.6═H, and, if necessary, alkylating the compound of formula (IV) wherein R.sub.6═H with a compound R.sub.5X, X being a halogen, preferably 1, and R.sub.5 being a (C.sub.1-C.sub.6) alkyl group, in order to obtain a compound of formula (IV) wherein R.sub.6═(C.sub.1-C.sub.6) alkyl, and the possible recovering of the compound of formula (IV).

13. A process for the preparation of a compound having the ##STR00062## following formula (V): R.sub.2 being as defined in claim 1, and R.sub.6 being H or a (C.sub.1-C.sub.6)alkyl group, said process comprising the steps of: preparing a compound of formula (I-1) with R being COOR.sub.a, using the process of claim 1, reacting the compound of formula (I-1) with methanol in the presence of a base, in order to obtain a compound of formula (V) wherein R.sub.6═H, and, if necessary, alkylating the compound of formula (V) wherein R.sub.6═H with a compound R.sub.5X, X being a halogen and R.sub.5 being a (C.sub.1-C.sub.6) alkyl group, in order to obtain a compound of formula (V) wherein R.sub.6═(C.sub.1-C.sub.6) alkyl, and the possible recovering of the compound of formula (V).

14. A process for the preparation of a compound having the following formula (VI): ##STR00063## R.sub.2 being a (C.sub.1-C.sub.6) alkoxy group, R.sub.7 being a (C.sub.2-C.sub.10)alkenyl group, and R.sub.8 being a (C.sub.1-C.sub.6)alkyl group, said process comprising the steps of: preparing a compound of formula (V) with R.sub.6 being a (C.sub.1-C.sub.6)alkyl group, using the process according to claim 13, reacting the compound of formula (V) with an alcohol R.sub.7OH in the presence of a catalyst and of N,N′-diisopropyl carbodiimide, in order to obtain a compound of formula (VI), and the possible recovering of the compound of formula (VI).

15. A process for the preparation of a compound having the following formula (VII): ##STR00064## R.sub.2 being as defined in claim 1, and R.sub.8 being a (C.sub.1-C.sub.6)alkyl group, said process comprising the steps of: preparing a compound of formula (I-1) with R being CHO, using the process according to claim 1, alkylating the compound of formula (I-1) with a compound R.sub.8X, X being a halogen for obtaining a compound having the following formula (III-1): ##STR00065## R.sub.2 and R.sub.8 being as defined above in formula (VII), reacting the compound of formula (III-1) with a Wittig reagent, in order to obtain a compound having the formula (VII), and the possible recovering of the compound of formula (VII).

16. A process for the preparation of a compound having the following ##STR00066## R′ and R.sub.2 being as defined in claim 1, and n being an integer varying from 1 to 6, said process comprising the steps of: preparing a compound of formula (I-2), using the process of claim 1, reacting the compound of formula (I-2) with a hydrogenation agent in order to obtain a compound having the following formula (VIII-1): ##STR00067## R′ and R.sub.2 being as defined in claim 1, reacting the compound of formula (VIII-1) in the presence of a base with a compound having the following formula (IX): ##STR00068## n being as defined above, and X being a halogen atom, in order to obtain a compound of formula (VIII), and the possible recovering of the compound of formula (VIII).

17. A process for the preparation of a compound having the following formula (X): ##STR00069## Alk being a (C.sub.1-C.sub.6)alkyl group, R.sub.2 being as defined in claim 1, and R.sub.9 being a (C.sub.2-C.sub.10)alkenyl group, said process comprising the steps of: preparing a compound of formula (I-1) with R being a (C.sub.1-C.sub.6) alkyl group, using the process of claim 1, reacting the compound of formula (I-1) with a compound R.sub.7X, X being a halogen in the presence of K.sub.2CO.sub.3 in a solvent, and the possible recovering of the compound of formula (X).

18. A compound having one of the following formulae: ##STR00070##

Description

EXAMPLES

[0217] Preparation of Compounds of Formula (I)

[0218] Vanillin, 2-methoxy-4-methylphenol and 2,6-dimethoxyphenol were supplied by Alfa Aesar; Eugenol was purchased from Sigma Aldrich and Acetovanillon was bought from Acros organic.

[0219] Enzymatic Dimerization: General Procedure

[0220] A solution of 1.5 g of compound of formula (II) in 20 mL of acetone was added to 180 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was saturated in O.sub.2 for 5 min. Laccase from Trametes versicolor (20 U, 12.4 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight). This procedure is was adapted on 15 g in the case of vanillin.

[0221] Kinetic Investigation

[0222] The enzymatic dimerization general procedure is followed using vanillin and 0.1 mL of dioxane, used as reference is added in the solution. 0.4 mL of solution is sampled regularly, filtered and diluted in deuteriated acetone. The samples are analyzed by NMR. The vanillin conversion is extracted from the ratio of CHO peak integration at 9.81ppm and the dioxane peak integration at 3.63 ppm.

[0223] Observations

[0224] After introduction of the laccase, the uncolored solution turned to yellow, revealing the creation of radicals. After few minutes, a brown precipitate appeared.

Example 1

Preparation of compound (1)

[0225] ##STR00037##

[0226] A solution of 1.5 g of vanillin in 20 mL of acetone was added to 180 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was saturated in O.sub.2 for 5 min. Laccase from Trametes versicolor (20 U, 12.4 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight).

[0227] Yield: 96%

[0228] Analyses: [0229] Mass: 302.1 (100%), 303.1 (18%), 304.1 (2%); [0230] .sup.1H NMR: δ 9.85 (s, CHO), 7.50 (s, 2H Ar), 4.00 (s, OCH.sub.3); [0231] .sup.13C NMR: δ 191.04 (CHO), 150.70 (Ar—C), 147.95 (Ar—C), 128.30 (Ar—C), 127.69 (Ar—C),124.52 (Ar—C), 109.10 (Ar—C), 55.88 (OCH.sub.3).

Example 2

Preparation of Compound (2)

[0232] ##STR00038##

[0233] Compound (2) is prepared from 4-hydroxy-3-methoxy-benzonitrile with a yield of 95%.

4-Hydroxy-3-methoxybenzonitrile synthesis

[0234] 750 mg (5 mmol) of vanillin were dissolved in 15 mL of acetic acid. 520 mg of NH.sub.2OH.HCl (7.5 mmol) are added and the mixture was stirred and warmed at 110° C. for 2 h. The reaction was stopped by adding H.sub.2O, the organic product extracted using CH.sub.2Cl.sub.2, dried and purified by flash chromatography (Ethyl acetate/cyclohexane 3/7).

[0235] Dimerization

[0236] A solution of 1.5 g of compound of 4-hydroxy-3-methoxybenzonitrile in 20 mL of acetone was added to 180 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was io saturated in O.sub.2 for 5 min. Laccase from Trametes versicolor (20 U, 12.4 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight).

[0237] Analyses: [0238] Mass: 296.1 (100%), 297,1 (18%), 298.1 (2%); [0239] .sup.1H NMR: δ 9.91 (s, 2H, HO), 7.57 (s, 2H, Ar), 7.42 (s, 2H, Ar), 3.93 (s, 6H, OCH.sub.3); [0240] .sup.13C NMR: δ 148.63 (Ar—C), 147.85 (Ar—C), 128.05 (Ar—C), 124.56 (Ar—C), 119.45 (Ar—C), 114.03 (Ar—C), 100.30 (CN), 56.15 (OCH.sub.3).

Example 3

Preparation of Compound (3)

[0241] ##STR00039##

[0242] A solution of 1.5 g of compound of acetovanillone in 20 mL of acetone was added to 180 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was saturated in O.sub.2 for 5 min. Laccase from Trametes versicolor (20 U, 12.4 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight).

[0243] Compound (3) is prepared from acetovanillone with a yield of 92%.

[0244] Analyses: [0245] Mass: 330.1 (100%), 331.1 (18%), 332.2 (2%); [0246] .sup.1H NMR: δ 7.49 (s, 4H, Ar), 3.93 (s, 6H, OCH.sub.3), 2,56 (s, 6H, C═OCH.sub.3); [0247] .sup.13C NMR: δ 196.07 (OCH), 149.22 (Ar—C), 147.06 (Ar—C), 127.81 (Ar—C), 124.23 (Ar—C), 124.04 (Ar—C), 109.03 (Ar—C), 55.76 (OCH.sub.3), 26.25 (CH.sub.3).

Example 4

Preparation of Compound (4)

[0248] ##STR00040##

[0249] A solution of 1.5 g of compound of methylvanillate in 20 mL of acetone was added to 180 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was saturated in 0.sub.2 for 5 min. Laccase from Trametes versicolor (20 U, 12.4 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight).

[0250] Compound (4) is prepared from methylvanillate with a yield of 90%.

[0251] Methyl Vanillate Synthesis

[0252] 15 g of vanillic acid (0.09 mol) were dissolved in 75 mL of methanol. 2.1 mL of sulfuric acid were added and the mixture is stirred and warm to reflux for 8 h. After evaporation of methanol, the solid is dissolved in 60 mL of ethylacetate, washed with 30 mL of NaHCO.sub.3 solution, water (2 times) and brine (1 time). The organic phase is evaporated under reduced pressure.

[0253] Analyses: [0254] Mass: 362.1 (100%), 363.1 (20%) , 364.1 (2%); [0255] .sup.1H NMR: δ 9.60 (s, 2H, HO), 7.46 (s, 4H, Ar), 3.90 (s, 6H, OCH.sub.3), 3.80 (s, 6H, OCH.sub.3 ester); [0256] .sup.13C NMR: δ 166,04 (OCH.sub.3ester), 148.60 (Ar—C), 147.27 (Ar—C), 125.25 (Ar—C), 123.93 (Ar—C), 119.21 (Ar—C), 110.89 (Ar—C), 55.97 (OCH.sub.3), 51.75(OCH.sub.3 ester).

Example 5

Preparation of Compound (5)

[0257] ##STR00041##

[0258] A solution of 1.5 g of compound of 2-methoxy-4-methylphenol in 20 mL of acetone was added to 180 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was saturated in 0.sub.2 for 5 min. Laccase from Trametes versicolor (20 U, 12.4 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight).

[0259] Compound (5) is prepared from 2-methoxy-4-methylphenol with a yield of 92%.

[0260] Analyses: [0261] Mass: 274.1 (100%), 275.1 (18%), 276.1 (2%); [0262] .sup.1H NMR: δ 6.73 (s, 2H, Ar), 6.53 (s, 2H, Ar), 3.79 (s, 6H, OCH.sub.3), 2.23 (s, 6H, CH.sub.3); [0263] .sup.13C NMR: δ 147.52 (Ar—C), 140.99 (Ar—C), 126.92 (Ar—C),125.68 (Ar—C), 123.04 (Ar—C), 111.61 (Ar—C), 55.85 (OCH.sub.3), 20.65 (CH.sub.3).

Example 6

Preparation of Compound (6)

[0264] ##STR00042##

[0265] A solution of 1.5 g of compound of 2,6-dimethoxy-phenol in 20 mL of acetone was added to 180 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was saturated in O.sub.2 for 5 min. Laccase from Trametes versicolor (20 U, 12.4 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight).

[0266] Compound (6) is prepared from 2,6-dimethoxy-phenol with a yield of 90%.

[0267] Analyses: [0268] Mass: 304.1 (100%), 305.1 (18%), 318.1 (2%); [0269] .sup.1H NMR: δ 8.32 (s, 2H, HO), 6.82(s, 4H, Ar), 3,84 (s, 12H, OCH.sub.3).

Example 7

Preparation of Compound (7)

[0270] ##STR00043##

[0271] A solution of 1.5 g of compound of eugenol in 20 mL of acetone was added to 180 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was saturated in O.sub.2 for 5 min. Laccase from Trametes versicolor (20 U, 12.4 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight).

[0272] Compound (7) is prepared from eugenol with a yield of 87%.

[0273] Analyses: [0274] Mass: 327.2 (100%), 326.2 (20%), 328,3 (10%); [0275] .sup.1H NMR: δ 6.74 (s, 2H Ar), 6.52 (s, 2H Ar), 5.94 (q, 2H CH—CH.sub.2), 5.03 (d, 4H CH—CH.sub.2), 3.79 (s, OCH.sub.3), 3.27 (d, 2H CH.sub.2); [0276] .sup.13C NMR: δ 147.80 (Ar—C), 141.62 (Ar—C), 138.38 (CH—CH.sub.2), 129.57 (Ar—C), 125.67 (Ar—C), 122.62 (Ar—C), 115.28 (Ar—C), 105.56 (CH—CH.sub.2), 55.64 (OCH.sub.3), 39.19 (CH.sub.2).

[0277] The above results show several advantages of the process of the invention: [0278] It is a green reaction.

[0279] Indeed the divanillin formation occurs at room temperature, under oxygen which could be replaced by air. The solvent used shows a low toxicity. To ensure the solubility of vanillin into the reaction medium, the compound was totally dissolved into acetone (10%) before adding the acetate buffer (90%). [0280] The product extraction is easy and the purity is high (95%). Indeed, the solvent conditions allowed the reactant solubility while the so formed product precipitated. The precipitate was filtered off, washed with water and analyzed by mass spectroscopy, NMR, and HPLC. [0281] A low quantity of enzyme is needed and can be reused. The experiments of the above examples were performed using 20 U of laccase. This amount is the minimal amount necessary to reach more than 85% conversion after 24 h. With 5 U or 10 U, 50% conversion is reached after 24 h.

[0282] The experiments are as follows: [0283] 5U: [0284] A solution of 1.5 g of compound of vanillin in 25 mL of acetone was added to 225 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was saturated in O.sub.2 for 5 min. Laccase from Trametes versicolor (5 U, 3.1 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight) and weighted. [0285] 10U: [0286] A solution of 1.5 g of compound of vanillin in 25 mL of acetone was added to 225 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was saturated in O.sub.2 for 5 min. Laccase from Trametes versicolor (10 U, 6.2 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight) and weighted.

[0287] 20U:

[0288] A solution of 1.5 g of compound of vanillin in 25 mL of acetone was added to 225 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was saturated in O.sub.2 for 5 min. Laccase from Trametes versicolor (20 U, 12.4 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight) and weighted.

[0289] 50U:

[0290] A solution of 1.5 g of compound of vanillin in 25 mL of acetone was added to 225 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was saturated in O.sub.2 for 5 min. Laccase from Trametes versicolor (50 U, 31 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight) and weighted.

[0291] 100U:

[0292] A solution of 1.5 g of compound of vanillin in 25 mL of acetone was added to 225 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was saturated in O.sub.2 for 5 min. Laccase from Trametes versicolor (100 U, 62 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight) and weighted.

[0293] The results of the above experiments are as follows:

TABLE-US-00001 Laccase units Yield (%) 100 85 50 85 20 87 10 54 5 56 [0294] Kinetic studies were realized and showed a good conversion, over 85% (not over due to NMR sensitivity) and a very high yield, over 90% after 24 h. [0295] The fact the divanillin precipitates while vanillin is still soluble allows the solution to be reused for a new reaction after filtration of divanillin.

[0296] Refill Procedure [0297] After 24 h of reaction, the precipitate was filtered and vanillin was added in the solution which was saturated in oxygen again. This experiment was repeated 8 times and the yield was still as high as 95%. [0298] The following experiment was carried out: [0299] A solution of 1.5 g of compound of vanillin in 25 mL of acetone was added to 225 mL of NaOAc buffer (0.1 M, pH 5.0). The solution was saturated in 0.sub.2 for 5 min. Laccase from Trametes versicolor (50 U, 31 mg) was added and the reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight) and weighted. The filtrate was kept. 1.5 g of vanillin was added in the solution which was saturated in oxygen again. The reaction was stirred at room temperature for 24 hours. The precipitate was filtered, washed with water and dried under vacuum (at 100° C. overnight) and weighted. This experiment was repeated 8 times.

TABLE-US-00002 Yield (%) 1st reaction 84 Refill 1 95 Refill 2 84 Refill 3 93 Refill 4 80 Refill 5 85 Refill 6 95 Refill 7 92 Refill 8 96

[0300] Chemical Modifications of Compounds of Formula (i)

[0301] Sodium borohydride, potassium hydroxide, triphenylphosphine, allyl bromide were supplied by Alfa Aesar.

[0302] Sodium acetate, acetic acid, laccase, hydroxylamine hydrochloride, sulfuric acid, iodomethane, 4-toluenesulfonic acid and N,N’-diisopropylcarbodiimide were io purchased from Sigma Aldrich.

[0303] 4-dimethylaminopyridine was bought from Acros organic, potassium carbonate was supplied by Prolabo, potassium tert-butoxide was purchased at ABCR and epichlorohydrine was bought at TCI.

Example 8

Preparation of Compound (8)

[0304] ##STR00044##

[0305] 20 mmol of divanillin (≈6 g) were dissolved in 100 mL of ethanol. The flask was put in an ice bath and 3.6 g of sodium borohydride (100 mmol) were added slowly. Then the mixture was stirred at room temperature for 30 min. 45 mL of water were added to stop the reaction and the solution is acidified with HCl to pH 7 and warmed for 5 min at 50° C. The solvent was evaporated; the resulting solid was solubilized in dichloromethane and washed 3 times with water. Yield: 80%.

[0306] Analyses: [0307] .sup.1H NMR: δ 8.25 (s, OH phenol), 6.9 (s, 2H Ar), 6.73 (s, 2H Ar), 5.065 (t, 2H OH), 4.46 (d, 4H CH.sub.2OH), 3.87 (s, OCH.sub.3); [0308] .sup.13C NMR: δ 151.14 (Ar—C), 149.67 (Ar—C), 128.81 (Ar—C), 127.36 (Ar—C), 120.94 (Ar—C), 108.59 (Ar—C), 63.78 (CH.sub.2OH), 55.32 (OCH.sub.3).

Example 9

Preparation of Compound (9)

[0309] ##STR00045##

[0310] 26 mmol of divanillin (≈8 g) were dissolved in 120 mL of DMF. 15.2 g of potassium carbonate (110 mmol) were added before a slow addition of 9.6 mL of iodomethane (158 mmol). After 15 h of stirring at 80° C., the mixture was filtered and the resulting solution poured into cold water. The methylated compound which precipitated was filtered off and dried under vacuum. Yield: 80%.

[0311] Analyses: [0312] .sup.1H NMR: δ 9.94 (s, CHO), 7.58 (s, 2H Ar), 7.55 (s, 2H Ar), 3.95 (s, OCH.sub.3), 3.68 (s, OCH.sub.3); [0313] .sup.13C NMR: δ 191.83 (CHO), 152.80 (Ar—C), 151.21 (Ar—C), 131.90 (Ar—C), 131.58 (Ar—C), 125.96 (Ar—C), 111.14 (Ar—C), 60.47 (OCH.sub.3), 55.93 (OCH.sub.3).

Example 10

Preparation of Compound (10)

[0314] ##STR00046##

[0315] 20 mmol of methylated divanillin (≈6 g) were dissolved in 100 mL of ethanol.

[0316] The flask was put in an ice bath and 3.6 g of sodium borohydride (100 mmol) were added slowly. Then the mixture was stirred at room temperature for 30 min. 45 mL of water were added to stop the reaction and the solution is acidified with HCl to pH 7 and warmed for 5 min at 50° C. The solvent was evaporated; the resulting solid is was solubilized in dichloromethane and washed 3 times with water. Yield: 85%.

[0317] Analyses: [0318] .sup.1H NMR: δ 6.99 (s, 2H Ar), 6.67(s, 2H Ar), 5.15 (t, 2H OH), 4.47 (d, 4H CH2OH), 3.83 (s, OCH.sub.3), 3.51 (s, OCH.sub.3); [0319] .sup.13C NMR: δ 151.93 (Ar—C), 144.86 (Ar—C), 137.52 (Ar—C), 132.14 (Ar—C), 120.27 (Ar—C), 110.20 (Ar—C), 62.69 (CH.sub.2OH), 59.83 (OCH.sub.3), 55.53 (OCH.sub.3).

Example 11

Preparation of Compound (11)

[0320] ##STR00047##

[0321] 26 mmol of dimethyl divanillate (≈8 g) were dissolved in 120 mL of DMF. 15.2 g of potassium carbonate (110 mmol) were added before a slow addition of 9.6 mL of iodomethane (158 mmol). After 15 h of stirring at 80° C., the mixture was filtered and the resulting solution poured into cold water. The methylated compound which precipitated was filtered off and dried under vacuum. Yield: 80%.

[0322] Analyses: [0323] .sup.1H NMR: δ 7.59 (s, 2H Ar), 7.41 (s, 2H Ar), 3.92 (s, OCH.sub.3), 3.84 (s, OCH.sub.3), 3.62 (s, OCH.sub.3); [0324] .sup.13C NMR: δ 165.63 (OCH.sub.3ester), 152.16 (Ar—C), 149.95 (Ar—C), 131.19 (Ar—C), 124.44 (Ar—C), 123.81 (Ar—C), 112.43 (Ar—C), 60.38 (OCH.sub.3), 55.73 (OCH.sub.3 ester), 52.81(OCH.sub.3).

Example 12

Preparation of Compound (12)

[0325] ##STR00048##

[0326] 7 mmol of methylated dimethyl divanillate (≈2.5 g) were dissolved in 10 mL of methanol. 2.5 g of KOH (45 mmol) were added and the solution was warmed to reflux for 9 h. The reaction was stopped with 2.5 mL of water. The remaining diester is extracted with diethylether. The aqueous phase was acidified with HCl and the diacid precipitated. Yield: 94%.

[0327] Analyses: [0328] .sup.1H NMR: δ 7.63 (s, 2H Ar), 7.42 (s, 2H Ar), 3.96 (s, OCH.sub.3), 3.64 (s, OCH.sub.3); [0329] .sup.13C NMR: δ 166.72 (COOH), 152.21 (Ar—C), 149.91 (Ar—C), 131.06 (Ar—C), 123.86 (Ar—C), 112.88 (Ar—C), 59.89 (Ar—C), 55.84 (OCH.sub.3), 55.86 (OCH.sub.3).

Example 13

Preparation of Compound (13)

[0330] ##STR00049##

[0331] 7 mmol of dimethyl divanillate (≈2.5 g) were dissolved in 10 mL of methanol. 2.5 g of KOH (45 mmol) were added and the solution was warmed to reflux for 9 h. The reaction was stopped with 2.5 mL of water. The remaining diester is extracted with diethylether. The aqueous phase was acidified with HCl and the diacid precipitated. Yield: 92%.

[0332] Analyses: [0333] .sup.1H NMR: δ 7.52 (s, 2H Ar), 7.48 (s, 2H Ar), 3.96 (s, OCH.sub.3); [0334] .sup.13C NMR: δ 166.91 (COOH), 148.20 (Ar—C), 147.24 (Ar—C), 125.23 (Ar—C), 124.06 (Ar—C), 120.66 (Ar—C), 111.20 (Ar—C), 55.84 (OCH.sub.3).

Example 14

Preparation of Compound (14)

[0335] ##STR00050##

[0336] 3 g of dimethyl divanillate (16 mmol of acid functional groups) was dissolved in 80 ml of CH.sub.2Cl.sub.2 under stirring. Subsequently 16 mmol of p-toluene sulfonic acid/4-dimethylaminopyridine catalyst in a molar ratio 1/1.2 was added. The flask was placed in an ice bath and subsequently an excess of undecenol (4.8 mL, 24 mmol) was added to the solution. Finally, N,N′-diisopropyl carbodiimide (DIPC, 7.2 ml 46 mol) was added dropwise under stirring. The reaction was left under stirring for 72 hours at room temperature. Afterwards the solution was washed three times with water, dried and the solvent was removed under reduced pressure. The product was a yellow brown viscous liquid. The acylurea formed was eliminated by filtration after dissolution of the product in toluene. The remaining reactants were eliminated by silica column purification using dichloromethane. Yield: 60%

[0337] Analyses:

[0338] .sup.1H NMR: δ 7.37 (s, 2H Ar), 7.58 (s, 2H Ar), 4.92 (m, 3H CH—CH.sub.2), 4.25 (t, 2H CH.sub.2—COO), 3.92 (s, OCH.sub.3), 3.62 (s, OCH.sub.3), 1.97 (m, 3H -CH.sub.2-), 1.67 (m, 2H —CH.sub.2—), 1.23 (m, 13H —CH.sub.2—);

[0339] .sup.13C NMR: δ 164.84 (COO), 152.12 (Ar—C), 150.30 (Ar—C), 138.56 (C=C), 131.26 (Ar—C), 125.08 (Ar—C), 123.50 (Ar—C), 114.34 (C=C), 112.55 (Ar—C), 64.59 (OCH.sub.2), 60.23 (OCH.sub.3), 56,06 (OCH.sub.3), 25.40-32.99 (CH.sub.2).

Example 15

Preparation of Compound (15)

[0340] ##STR00051##

[0341] Divinyl Synthesis: Wittig Reaction (15)

[0342] 3 g of triphenylphosphine (11.4 mmol) were dissolved in 30 mL of toluene. 0.7 mL of iodomethane (11.4 mmol) was added dropwise. The mixture is stirred to reflux at 120° C. under nitrogen flow. Methyltriphosphoniumiodide precipitated and was filtered off and dried under vaccum.

[0343] To a solution of methyltriphosphoniumiodide (8.8 g, 22 mmol) in dry THF (36 mL), 2.7 g of potassium tert-butoxide were added at 0° C. After 1 h of stirring at room temperature under nitrogen, 3.2 g of divanillin (10 mmol) was added. The mixture is stirred at 35° C. for 24 h. The solution is diluted with 75 mL of dichloromethane, washed with water and 2 times with brine. The solvent of the organic phase is evaporated. The remaining reactants were eliminated by silica column purification using dichloromethane/cyclohexane 50/50. Yield: 75%

[0344] Analyses: [0345] .sup.1H NMR: δ 7.17 (s, 2H Ar), 6.83 (s, 2H Ar), 6.70 (q, 2H CH—CH.sub.2), 5.77 (d, 2H CH—CH.sub.2), 5.19 (d, 2H CH—CH.sub.2), 3.87 (s, OCH.sub.3), 3.53 (s, OCH.sub.3); [0346] .sup.13C NMR: δ 152.34 (Ar—C), 145.84 (Ar—C), 136.25 (CH—CH.sub.2), 132.66 (Ar—C), 132.01 (Ar—C), 120.82 (Ar—C), 113.30 (CH—CH.sub.2), 109.25 (Ar—C), 59.94 (OCH.sub.3), 55.53 (OCH.sub.3).

Example 16

Preparation of Compound (16)

[0347] ##STR00052##

[0348] 6 g of 2,6-dimethoxy phenol dimer (20 mmol) were dissolved in 180 mL of ethanol. The flask was put in an ice bath and 6.75 g of sodium borohydride (178 mmol) were added slowly. Then the mixture was stirred at room temperature for 30 min. 80 mL of water were added to stop the reaction and the solution is acidified with HCl to pH 7 and warmed for 5 min at 50° C. The solvent was evaporated; the resulting solid was solubilized in dichloromethane and washed 3 times with water. Yield: 78%.

[0349] Analyses: [0350] .sup.1H NMR: δ 8.34 (s, 1H OH), 6.88 (s, 2H Ar), 3.90 (s, OCH.sub.3); [0351] .sup.13C NMR: δ 148.13 (Ar—C), 134.98 (Ar—C), 131.00 (Ar—C), 104.12 (Ar—C), 55.98 (OCH.sub.3).

Example 17

Preparation of Compound (17)

[0352] ##STR00053##

[0353] 5 g of reducted 2,6-dimethoxy phenol dimer (16 mmol) were dissolved in 16 mL of epichlorohydrin. 7.9 g of potassium hydroxide (141 mmol) and 1 g of tetrabutylammonium bromide (3.1 mmol) were added and the solution is stirred at room temperature for 4 h. The product is extracted with dichloromethane and washed with water. Dichloromethane and epichlorohydrin are removed from the organic phases under vacuum. Yield: 95%.

[0354] Analyses: [0355] .sup.1H NMR: δ 6.89 (s, 2H Ar), 4.11 (dd, 1H OCH.sub.2), 3.87 (s, OCH.sub.3), 3.76 (q, 1H OCH.sub.2), 2.74 (t, CH), 2.60 (q, CH.sub.2 epoxy), 2.50 (q, CH.sub.2 epoxy); [0356] .sup.13C NMR: δ 152.73 (Ar—C), 136.37 (Ar—C), 135.84, 104.81 (Ar—C), 173.55 (OCH.sub.2), 56.03 (OCH.sub.3), 50.11 (CH epoxy), 43.02 (CH.sub.2 epoxy).

Example 18

Preparation of Compound (18)

[0357] ##STR00054##

[0358] 26 mmol of bisphenol compound (7) (≈8 g) were dissolved in 120 mL of DMF. 15.2 g of potassium carbonate (110 mmol) were added before a slow addition of 9.6 mL of iodomethane (158 mmol). After 15 h of stirring at 80° C., the mixture was filtered and the resulting solution poured into cold water. The methylated compound which precipitated was filtered off and dried under vacuum. Yield: 85%.

[0359] Analyses: [0360] .sup.1H NMR: δ 6.93 (s, 2H Ar), 6.61 (s, 2H Ar), 6.03 (q, 2H CH—CH.sub.2), 5.13 (d, 4H CH—CH.sub.2), 3.89 (s, OCH.sub.3), 3.56 (s, OCH.sub.3), 3.42 (d, 2H CH.sub.2); [0361] .sup.13C NMR: δ 152.02 (Ar—C), 144.15 (Ar—C), 137.53 (CH—CH.sub.2), 134.73 (Ar—C), 132.29 (Ar—C), 122.19 (Ar—C), 115.77 (Ar—C), 112.15 (CH—CH.sub.2), 59.80 (OCH3), 55.44 (OCH.sub.3), 39.29 (CH.sub.2).

Example 19

Preparation of Compound (19)

[0362] ##STR00055##

[0363] 26 mmol of 2-methoxy-4-methoxyphenol dimer were dissolved in 120 mL of DMF. 15.2 g of potassium carbonate (110 mmol) were added before a slow addition of 19.1 g of allylbromide (156 mmol). After 15 h of stirring at 80° C., the mixture was filtered and the resulting solution poured into cold water. The methylated compound which precipitated was filtered off and dried under vacuum. Yield: 50%.

[0364] Analyses: [0365] .sup.1H NMR: δ 6.84 (s, 2H, Ar), 6.55 (s, 2H, Ar), 5.70 (m, 2H, CH—CH.sub.2), 4.99 (dd, 4H, CH—CH.sub.2), 4.21 (d, 4H, OCH.sub.2), 3.80 (s, 6H, OCH.sub.3), 2.26 (s, 6H, CH.sub.3); [0366] .sup.13C NMR: δ 151.98 (Ar—C), 142.92 (Ar—C), 134.95 (CH—CH.sub.2), 13.30 (Ar—C), 132.17 (Ar—C), 123.03 (Ar—C), 116.43 (CH—CH.sub.2), 112.67 (Ar—C), 73.21 (CH.sub.2), 55.36 (OCH.sub.3), 20.78 (CH.sub.3).