Process for the synthesis of polyhydroxystilbene compounds
The invention relates to a process for the synthesis of stilbene derivatives of formula (I)-(E) or (I)-(Z) in which R represents hydrogen or an OH group, by deprotection in the presence of an aluminum halide and of a tertiary amine of a compound of formula (II)-(E) or (II)-(Z) in which A represents hydrogen or an OR′ 1 group, and R 1 , R 2 , R 3 and R′ 1 independently represent an alkyl or aralkyl group.
1. A process for the synthesis of an (E)-stilbene derivative of formula (I)-(E) or a (Z)-stilbene derivative of formula (I)-(Z)
wherein:
R is hydrogen or an OH group,
R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are independently a hydrogen or a substituent selected from the group consisting of:
a halogen;
a nitro group;
a linear or branched C 1 -C 6 alkyl group;
a linear or branched C 2 -C 6 alkenyl group;
a C 3 -C 10 cycloalkyl group;
a cycloalkylalkyl group wherein the cycloalkyl and alkyl groups are as defined above;
a monocyclic, bicyclic or tricyclic C 6 -C 14 aryl group;
a C 7 -C 16 aralkyl group; and
a C(═O)R 10 group wherein R 10 is a linear or branched C 1 -C 6 alkyl group, a C 3 -C 10 cycloalkyl group, a cycloalkylalkyl group wherein the cycloalkyl and alkyl groups are as defined above, a monocyclic, bicyclic or tricyclic C 6 -C 14 aryl group, a C 7 -C 16 aralkyl group, an OR 11 group wherein R 11 is a hydrogen, a linear or branched C 1 -C 6 alkyl group, a C 3 -C 10 cycloalkyl group, a cycloalkylalkyl group wherein the cycloalkyl and alkyl groups are as defined above, a monocyclic, bicyclic or tricyclic C 6 -C 14 aryl group or a C 7 -C 16 aralkyl group, or an NR 12 R 13 group wherein R 12 and R 13 independently are a hydrogen, a linear or branched C 1 -C 6 alkyl group, a C 3 -C 10 cycloalkyl group, a cycloalkylalkyl group wherein the cycloalkyl and alkyl groups are as defined above, a monocyclic, bicyclic or tricyclic C 6 -C 14 aryl group or a C 7 -C 16 aralkyl group;
wherein all the above alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl radicals may be unsubstituted or substituted,
comprising the step of deprotecting a compound of formula (II)-(E) or (II)-(Z)
wherein A is a hydrogen or an OR′ 1 group and R 1 , R 2 , R 3 and R′ 1 independently are a linear or branched C 1 -C 6 alkyl group or a C 7 -C 16 aralkyl group, optionally substituted on the aryl part by one or more C 1 -C 4 alkoxy or halogen groups,
wherein the deprotecting step is carried out by the use of an aluminium halide and of a tertiary amine of formula NR a R b R c wherein R a , R b and R c are independently a linear or branched C 1 -C 4 alkyl group.
2. A process according to claim 1 for the preparation of an (E)-stilbene derivative of formula (I)
wherein R is a hydrogen or an OH group,
comprising the step of deprotecting a compound of formula (II)
wherein A is a hydrogen or an OR′ 1 , group and R 1 , R 2 , R 3 and R′ 1 , are independently a linear or branched C 1 -C 6 alkyl group or a C 7 -C 16 aralkyl group, optionally substituted on the aryl part by one or more C 1 -C 4 alkoxy or halogen groups,
wherein the deprotecting step is carried out by the use of an aluminium halide and of a tertiary amine of formula NR a R b R c wherein R a , R b and R c are independently a linear or branched C 1 -C 4 alkyl group.
3. A process according to claim 1 , wherein R 1 , R 2 , R 3 and R′ 1 , in the formula (II)-(E) or (II)-(Z) are independently a linear or branched C 1 -C 3 alkyl group or a benzyl group optionally substituted on the phenyl part by one or more C 1 -C 4 alkoxy or halogen groups, and wherein R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are as defined above.
4. A process according to claim 2 , wherein R 3 and R′ 1 in the formula (II) are independently a linear or branched C 1 -C 3 alkyl group or a benzyl group optionally substituted on the phenyl part by one or more C 1 -C 4 alkoxy or halogen groups.
5. A process according to claim 2 , wherein R 1 , R 2 , R 3 and R′ 1 in the formula (II)-(E) or (II)-(Z) or (II) are independently a methyl group or a benzyl group.
6. A process according to claim 1 , wherein the aluminium halide is selected from the group consisting of aluminium chloride, aluminium bromide and aluminium iodide.
7. A process according to claim 6 , wherein the aluminium halide is aluminium chloride.
8. A process according to claim 1 , wherein the tertiary amine is selected from the group consisting of triethylamine, tripropylamine, tributylamine, N,N-dimethylethylamine, N,N-diethylmethylamine and N,N-dimethylbutylamine.
9. A process according to claim 8 , wherein the tertiary amine is triethylamine.
10. A process according to claim 1 , wherein the aluminium halide to tertiary amine molar ratio is between 1:1 and 1:2.
11. A process according to claim 10 , wherein the aluminium halide to tertiary amine molar ratio is between 1:1.5 and 1:1.6.
12. A process according to claim 1 , wherein between 1 and 10 molar equivalents of aluminium halide and between 1 and 20 molar equivalents of tertiary amine per ether group to be deprotected in the compounds of formula (II)-(E) or (II)-(Z) is used.
13. A process according to claim 12 , wherein between 1 and 4 molar equivalents of aluminium halide and between 1 and 6 molar equivalents of tertiary amine per ether group to be deprotected in the compounds of formula (II)-(E) or (II)-(Z) is used.
14. A process according to claim 1 , wherein an aluminium halide/tertiary amine of formula NR a R b R c complex is used in the deprotecting step.
15. A process according to claim 1 , wherein the deprotecting step is carried out in the presence of at least one solvent.
16. A process according to claim 15 , wherein the solvent is chlorobenzene or toluene.
17. A process according to claim 1 , wherein the deprotecting step is carried out at a temperature of between 50° C. and 120° C.
18. A process according to claim 4 , wherein R 1 , R 2 , R 3 and R′ 1 in the formula (II)-(E) or (II)-(Z) or (II) are independently a methyl group or a benzyl group.
19. A process according to claim 2 , wherein between 1 and 10 molar equivalents of aluminium halide and between 1 and 20 molar equivalents of tertiary amine per ether group to be deprotected in the compound of formula (II) is used.
20. A process according to claim 19 , wherein between 1 and 4 molar equivalents of aluminium halide and between 1 and 6 molar equivalents of tertiary amine per ether group to be deprotected in the compound of formula (II) is used.
21. A process according to claim 1 , wherein the deprotecting step is carried out at a temperature of between 80° C. and 100° C.
22. A process according to claim 1 , wherein the deprotecting step is carried out without solvent.