Membrane enhanced polymer synthesis
This invention relates to the synthesis of polymers. More specifically, the present invention relates to the synthesis of heterobifunctional polymers and polymers with narrow and mono-disperse molecular weight distributions, and especially to the application of membranes to the synthesis of these polymers.
1. A process for the preparation of heterobifunctional or mono-disperse polymers comprising the following steps:
(a) reacting an excess of an initial polymer dissolved in a solvent with a branch point molecule to form a polymer mixture containing at least the initial polymer and a conjugate comprising at least two polymer molecules covalently bound to the branch point molecule such that each polymer molecule has a terminal which is bound to the branch point molecule and at least one unbound terminal;
(b) contacting the polymer mixture with a semi-permeable membrane which has a rejection for the conjugate which is greater than the rejection for the initial polymer, so that the ratio between the concentrations of the conjugate and the initial polymer in the retentate is increased; and
(c) cleaving the polymer from the branch point molecule of the conjugate;
wherein the at least one unbound terminal of the polymer molecule of the conjugate is chemically modified to either modify the functionality of the unbound terminal of the polymer or add additional monomer or polymer units to the polymer and said modification occurs either prior to or subsequent to step (b) such that the polymer cleaved from branch point molecule comprises the initial polymer comprising at least one chemically modified terminal.
2. The process as in claim 1 , wherein the process is a process for the preparation of heterobifunctional polymers and said chemical modification involves the removal of any protecting groups that may be present at the unbound terminal of the polymer followed by the functionalisation of the unbound terminal.
3. The process according to claim 1 , wherein the process is a process for the preparation of monodisperse polymer and said chemical modification involves the removal of any protecting groups that may be present at the unbound terminal followed by reaction of the unbound terminal of the polymer present in the conjugate with another polymer or monomer unit.
4. The process according to claim 1 , wherein the chemical modification of the polymer occurs prior to step (b).
5. The process according to claim 1 , wherein the chemical modification occurs subsequent to step (b).
6. The process according to claim 1 in which more than one membrane filtration step is used to purify the conjugate or its derivatives from the initial polymer, reagents and by-products, by contacting mixtures containing the conjugate or its derivatives and the initial polymer, reagents and by-products with the semi-permeable membrane which has a rejection for the conjugate or its derivatives which is greater than the rejection for at least one of the initial polymer, reagents and by-products present, so that the ratio between the concentrations in the retentate of the conjugate or one of its derivatives and at least one of the initial polymer, reagents and by-products, is increased.
7. The process according to claim 1 , in which additional solvent is added to the retentate and permeated through the membrane to remove further initial polymer, by-products or excess reagents by diafiltration.
8. The process according to claim 7 in which the additional solvent is the same as the reaction solvent.
9. The process according to claim 1 in which the additional solvent is not the same as the reaction solvent, and in which the polymer product is maintained dissolved in the solvents throughout the diafiltration.
10. The process according to claim 1 in which the initial polymer is selected from the group consisting of: polyethylene glycol, polypropylene glycol, polybutylene oxide and block copolymers of any of these, polypropylene oxide block copolymers of polypropylene oxide and polyethylene glycol, polydimethylsiloxane (PMDS), polybutadiene and polyisoprene, nylons and polyesters formed with either the di-acid in excess to generate polymers terminating in carboxylic acids, or the di-amine/diol in excess to generate polymers terminating with amino/hydroxyl groups, and polyethylene sulphide.
11. The process as claimed in claim 1 in which the linkage between the initial polymer and the branch point molecule is selected from the group consisting of: ether, ester, and amide, linkages, including phosphate esters, silyl ethers, acetals, orthoesters, thio-ethers, and olefin bonds.
12. The process according to claim 1 in which the membrane is a polymeric membrane.
13. The process according to claim 1 in which the membrane is a ceramic membrane.
14. The process according to claim 2 , wherein the chemical modification of the polymer occurs prior to step (b).
15. The process according to claim 3 , wherein the chemical modification of the polymer occurs prior to step (b).
16. The process according to claim 2 , wherein the chemical modification occurs subsequent to step (b).
17. The process according to claim 3 , wherein the chemical modification occurs subsequent to step (b).
18. The process according to claim 2 in which more than one membrane filtration step is used to purify the conjugate or its derivatives from the initial polymer, reagents and by-products, by contacting mixtures containing the conjugate or its derivatives and the initial polymer, reagents and by-products with the semi-permeable membrane which has a rejection for the conjugate or its derivatives which is greater than the rejection for at least one of the initial polymer, reagents and by-products present, so that the ratio between the concentrations in the retentate of the conjugate or one of its derivatives and at least one of the initial polymer, reagents and by-products, is increased.
19. The process according to claim 3 in which more than one membrane filtration step is used to purify the conjugate or its derivatives from the initial polymer, reagents and by-products, by contacting mixtures containing the conjugate or its derivatives and the initial polymer, reagents and by-products with the semi-permeable membrane which has a rejection for the conjugate or its derivatives which is greater than the rejection for at least one of the initial polymer, reagents and by-products present, so that the ratio between the concentrations in the retentate of the conjugate or one of its derivatives and at least one of the initial polymer, reagents and by-products, is increased.