Preparation of phenyl compounds

Abstract

The invention relates to a method for preparing a compound comprising two phenyl groups by reacting a bisfuranic compound with a dienophile; and to such compounds.

Claims

1. A method for preparing a compound comprising two phenyl groups by reacting a bisfuranic compound with a dienophile, wherein the dienophile is an alkyne or an alkene and wherein the bisfuranic compound is according to any of the formulae (IIa-IId) ##STR00035## wherein the furanic moieties are optionally substituted, and wherein each R.sub.2 is independently H, a heteroatom, a halogen, or linear or branched C.sub.1-C.sub.8 alkyl, wherein said alkyl is optionally further substituted by halogens and/or heteroatoms, each R.sub.3 is independently selected from the group consisting of H, a halogen, a heteroatom functional group, and optionally with halogen or heteroatom substituted and/or optionally heteroatom containing C.sub.1-C.sub.40 hydrocarbyl group, wherein two of said R.sub.3 groups can be joined to form a ring, or wherein two of said R.sub.3 groups on the same atom are combined to form a substituent having a double bond with said atom, and wherein R.sub.6 is selected from the group consisting of a heteroatom functional group and optionally with halogen or heteroatom substituted and/or optionally heteroatom containing C.sub.1-C.sub.40 hydrocarbyl group.

2. The method according to claim 1, wherein the dienophile is an alkene according to formula (IIIa) or an alkyne according to formula (IIIb) or ##STR00036## wherein R.sub.5 is an electron withdrawing group EWG, and in case of an alkyne according to formula (IIIb), R.sub.5 is EWG or selected from the same group as R.sub.3, wherein R.sub.4 is H, linear or branched C.sub.1-C.sub.8 alkyl, or EWG, wherein EWG is independently selected from the group consisting of CN, NO.sub.2, CO.sub.2X, C(O)NX, C(NY)X, CF.sub.3, CCl.sub.3, CBr.sub.3, Cl.sub.3, SO.sub.2X, SO.sub.3X, COH, COX, COF, COCl, COBr, COI, wherein X and Y are independently selected from the group consisting of H and linear or branched C.sub.1-C.sub.8 alkyl, optionally substituted with halogens and optionally polymer-supported.

3. The method according to claim 2, wherein R4 is hydrogen.

4. The method according to claim 2, wherein the bisfuranic compound comprises a backbone structure according to formula (I) ##STR00037## wherein R.sub.1 is a linking group or is a covalent bond, and wherein the furanic moieties are optionally substituted, wherein the dienophile is an alkyne according to formula (IIIb) and wherein the compound comprising two phenyl groups is a bisphenol compound according to formula (VII): ##STR00038## wherein in each phenyl group, R.sub.5 is independently at the 2 or 3 position.

5. The method according to claim 2, wherein an alkyne dienophile is used and wherein the product is a bisphenol.

6. The method according to according to claim 2, wherein the dienophile is an alkene with formula (IIIa), wherein R.sub.4 is H and R.sub.5 is SO.sub.3X, wherein X is H or linear or branched C.sub.1-C.sub.8 alkyl, optionally substituted with halogens.

7. The method according to claim 1, wherein the reaction is catalysed with a Lewis acid.

8. The method according to claim 1, comprising further reacting the compound comprising two phenyl groups in one or more reactions selected from the group consisting of hydrolysis, reduction, oxidation, decarboxylation, decarbonylation, nucleophilic addition, olefination, rearrangement and combinations thereof.

9. The method according to claim 1, further comprising removing substituents from the formed phenyl groups.

10. A compound having formula (IX): ##STR00039## wherein each R.sub.5 is COH, SO.sub.2X, or SO.sub.3X, wherein X is H or linear or branched C.sub.1-C.sub.8 alkyl, said linear or branched C.sub.1-C.sub.6 alkyl substituted with halogens, wherein R.sub.6 is O, and and wherein R.sub.3 is as defined in claim 1, or a salt thereof.

11. A compound according to claim 10, having the formula ##STR00040## wherein X is H or linear or branched C.sub.1-C.sub.8 alkyl, optionally substituted with halogens, or a salt thereof.

12. The method according to claim 5, wherein the product is bisphenol A, AP, AF, B, BP, C1, C2, E, F, TMC or Z.

13. The method according to claim 9, comprising removing all substituents other than hydroxyl.

14. The method according to claim 12, wherein the product is bisphenol A, B, C1, E, F or Z.

Description

EXAMPLE 1

(1) ##STR00024##

(2) To a reactor was charged furfuryl alcohol (9.65 ml) and the stirring was started. Furan (145 ml) was then charged to the reactor. The mixture was cooled to 1 C., then trifluoroacetic acid (10 g) was dropwise. This was stirred for 36 hours at 1 C. then the mixture was washed with aqueous saturated sodium bicarbonate solution (2200 ml), then the organics were dried (MgSO.sub.4) filtered, and reduced to an viscous liquid by rotary evaporation. This crude mixture was then subjected to distillation, with the collected product distilling at a head temperature of 76 C. and a pressure of 16 mbar. This yielded 2,2-difurylmethane as a light yellow liquid (9.89 g, 60%). The structure was confirmed by 1H NMR.

EXAMPLE 2

(3) ##STR00025##

(4) 2,2-difurylmethane (715 mg) was charged to a reactor, then dimethyl acetylenedicarboxylate (1.8 ml) was added. The reactor was sealed, and the mixture was heated to 110 C., with stirring, for 2 hours. The reaction mixture was cooled to room temperature, and the reaction mixture was purified by flash chromatography to give the desired product as a yellow gum (1.57 g, 76%). The structure was confirmed by 1H NMR.

EXAMPLE 3

(5) ##STR00026##

(6) 2,2-difurylpropane (1 g) was charged to a reactor, then dimethyl acetylenedicarboxylate (2.1 ml) was added. The reactor was sealed, and the mixture was heated to 110 C., with stirring, for 2 hours, then 150 C. for 30 minutes. The reaction mixture was cooled to room temperature, and the reaction mixture was purified by flash chromatography to give the desired product as a light yellow gum (2.3 g, 88%). The structure was confirmed by 1H NMR.

EXAMPLE 4

(7) ##STR00027##

(8) The product of the Diels-Alder reaction between 2,2-difurylmethane (1039 mg) was charged to a reactor, then methanol (20 ml) was added and the mixture stirred until solution was achieved. To this was charged concentrated sulfuric acid (500 L), and the reactor was sealed, heated to 130 C., and held for 6 hours. The reaction mixture was cooled to 20 C., then the reaction mixture was diluted with dichloromethane (20 ml). The solution was then washed with aqueous saturated sodium bicarbonate solution (220 ml), then the organics were dried (MgSO.sub.4) filtered, and reduced to an viscous liquid by rotary evaporation. This liquid was purified by flash chromatography to give the desired product as a light yellow solid (631 mg, 60%). The structure was confirmed by 1H NMR.

EXAMPLE 5

(9) ##STR00028##

(10) The product of the Diels-Alder reaction between 2,2-difurylpropane (1.9 g) was charged to a reactor, then methanol (10 ml) was added and the mixture stirred until solution was achieved. To this was charged concentrated sulfuric acid (500 L), and the reactor was sealed, heated to 130 C., and held for 6 hours. The reaction mixture was cooled to 20 C., then the reaction mixture was diluted with dichloromethane (20 ml). The solution was then washed with aqueous saturated sodium bicarbonate solution (220 ml), then the organics were dried (MgSO.sub.4) filtered, and reduced to an viscous liquid by rotary evaporation. This liquid was was purified by flash chromatography to give the desired product as a brown gum (1443 mg, 75%). The structure was confirmed by 1H NMR.

EXAMPLE 6

(11) ##STR00029##

(12) To a reactor was charged the tetra-ester product (500 mg) and methanol (3.6 ml) and this was dissolved with stirring. To this was added 4M aqueous sodium hydroxide solution (3.6 ml) and the reaction mixture was heated to 60 C. and held for 4 hours. The reaction mixture was cooled to 20 C. then washed with DCM (210 ml). The aqueous layer was then acidified to pH1 with concentrated sulfuric acid, then the organics were extracted twice with EtOAc (215 ml). The combined organics were dried (Na.sub.2SO.sub.4), filtered and reduced to yield the desired product as a light brown gum (383 mg, 88%). The structure was confirmed by 1H NMR.

EXAMPLE 7

(13) ##STR00030##

(14) To a reactor was charged the tetra-ester product (750 mg) and methanol (5.1 ml) and this was dissolved with stirring. To this was added 4M aqueous sodium hydroxide solution (5.1 ml) and the reaction mixture was heated to 60 C. and held for 4 hours. The reaction mixture was cooled to 20 C. then washed with DCM (210 ml). The aqueous layer was then acidified to pH2 with concentrated sulfuric acid, then the organics were extracted twice with EtOAc (215 ml). The combined organics were dried (Na.sub.2SO.sub.4), filtered and reduced to yield the desired product as a brown gum (540 mg, 82%). The structure was confirmed by 1H NMR.

EXAMPLE 8

(15) ##STR00031##

(16) A reactor was charged with the 4,4-methylenebis[phenol-2,3-dicarboxylic acid] starting material (300 mg), copper(I) oxide (24 mg), 1,10-phenanthroline (60 mg), NMP (1200 L) and quinoline (330 L). The reactor was sealed, heated to 190 C. with microwave heating, and held for 1 hours, with stirring. The reaction mixture was cooled to ambient temperature then added to a stirred 1M solution of aqueous hydrochloric acid, and the organics were extracted with ethyl acetate (210 ml). The combined organics were washed with water, dried (Na.sub.2SO.sub.4), filtered and reduced by rotary evaporation to obtain the desired product as a light brown oil (101 mg, 63%). The structure of the product as bisphenol F (bis(4-hydroxyphenyl)methane) was confirmed by 1H NMR.

EXAMPLE 9DECARBOXYLATION WITH MODEL COMPOUNDS

(17) ##STR00032##

(18) A reactor was charged with 2-hydroxybenzoic acid (91 mg), copper(I) oxide (10 mg), 1,10-phenanthroline (24 mg), NMP (1 ml) and quinoline (364 mg, 333 L). The reactor was sealed, heated to 165 C., and held for 40 hours, with stirring. The reaction mixture was cooled to ambient temperature then brought directly onto silica and purified by flash chromatography, eluting with n-hexane and ethyl acetate. Appropriate fractions were collected for the product peak and were reduced by rotary evaporation to yield a yellow liquid. This was dissolved in dichloromethane (10 ml) and washed with 1N aqueous hydrochloric acid solution (210 ml) and subsequently with water (10 ml). The combined aqueous phase was extracted with dichloromethane (35 ml). All the organic phases were combined and dried (MgSO.sub.4), filtered, and reduced by rotary evaporation to obtain the desired product as orange oil (21 mg, 33%). The structure was confirmed as phenol by 1H NMR.

EXAMPLE 10DECARBOXYLATION WITH MODEL COMPOUNDS

(19) ##STR00033##

(20) A reactor was charged with 3-hydroxybenzoic acid (91 mg), copper(I) oxide (10 mg), 1,10-phenanthroline (24 mg), NMP (1 ml) and quinoline (364 mg, 333 L). The reactor was sealed, heated to 165 C., and held for 40 hours, with stirring. The reaction mixture was cooled to ambient temperature then brought directly onto silica and purified by flash chromatography, eluting with n-hexane and ethyl acetate. Appropriate fractions were collected for the product peak and were reduced by rotary evaporation to yield a yellow liquid. This was dissolved in dichloromethane (10 ml) and washed with 1N aqueous hydrochloric acid solution (210 ml) and subsequently with water (10 ml). The combined aqueous phase was extracted with dichloromethane (35 ml). All the organic phases were combined and dried (MgSO.sub.4), filtered, and reduced by rotary evaporation to obtain the desired product as orange oil (65 mg, 50%). The structure was confirmed as phenol by 1H NMR.

EXAMPLE 11DECARBOXYLATION WITH MODEL COMPOUNDS

(21) ##STR00034##

(22) A reactor was charged with 5-hydroxy-2-methylbenzoic acid (100 mg), copper(I) oxide (10 mg), 1,10-phenanthroline (24 mg), NMP (1 ml) and quinoline (364 mg, 333 L). The reactor was sealed, heated to 170 C., and held for 40 hours, with stirring. The reaction mixture was cooled to ambient temperature then brought directly onto silica and purified on a Reveleris X2 Flash Chromatography System, eluting with n-hexane and ethyl acetate. Appropriate fractions were collected for the product peak and were reduced by rotary evaporation to yield a yellow liquid. This was dissolved in dichloromethane (10 ml) and washed with 1N aqueous hydrochloric acid solution (210 ml) and subsequently with water (10 ml). The combined aqueous phase was extracted with dichloromethane (35 ml). All the organic phases were combined and dried (Na.sub.2SO.sub.4), filtered, and reduced by rotary evaporation to obtain the desired product as orange oil (33 mg, 47%). The structure was confirmed as 4-methylphenol by 1H NMR.