WO2014195401A2

WO2014195401A2 - Process for the preparation of silicone containing b-hydroxyl esters

Info

Publication number: WO2014195401A2
Application number: PCT/EP2014/061681
Authority: WO
Inventors: Ananth Iyer
Original assignee: Dsm Ip Assets B.V.
Priority date: 2013-06-05
Filing date: 2014-06-05
Publication date: 2014-12-11
Also published as: WO2014195401A3

Abstract

Disclosed herein are processes for forming silicon containing beta-hydroxyl esters. The processes are performed in the presence of a Cr(III) salt. The resulting reaction product mixture is purified by contacting it with amorphous silica and/or goethite.

Description

PROCESS FOR THE PREPARATION OF SILICONE CONTAINING BETA-

HYDROXYL ESTERS

Related Applications

This application claims priority to US Provisional Patent Application 61/831559, which is hereby incorporated by reference in its entirety.

Field

The present invention relates to a process for the preparation of silicone containing β-hydroxyl esters, in particular those containing at least one ethylenically unsaturated group.

Background

Silicone hydrogels find useful applications as biomedical materials, especially in the areas of contact lenses, wound care, etc. In many instances, these silicones are obtained by polymerization of monomers or pre-polymers.

β-hydroxyl esters of silicones are useful in silicone hydrogel formulations containing silicone and hydrophilic components. One such example is methyldi(trimethylsiloxy)sylylpropylglycerol methacrylate (SiGMA), mentioned in US patent 4139692.

β-hydroxyl esters are not easy to obtain synthetically and exclusively, particularly due to the presence of competing side reactions that produce undesirable byproducts. Non-silicone β-hydroxyl esters are prepared by the reaction of an alkyl or aryl epoxide with an alkyl or aryl carboxylic acid. Five reactions occur for the reaction between an organic acid and an organic epoxide. See, for example, Shecther, L, et al; Ind. & Eng. Chem.; vol. 48, (1956). These five reactions are shown below.

1 ) Ad

Condensation Esterification

Etherification

Disproportionation

Only reaction 1 (addition esterification) produces a desirable reaction product for a silicone hydrogel application. The other four reactions produce undesirable byproducts.

The occurrence of the various reactions is largely dependent on the catalyst employed. In a non-catalyzed system, reactions 1 , 3 and 4 predominantly occur. In acid catalyzed systems, reaction 4 (etherification) occurs predominantly. In base catalyzed systems, the intended reaction (reaction 1 ) is known to predominantly occur, although reaction 5 (disproportionation) is also reported, resulting in the formation of undesirable di-esters and glycol. Tertiary amines are among the various catalyst systems preferred in the past. For example trimethyl amine, dimethyl ethanol amine, methyl diethanol amine, ethyl methyl ethanol amine, dimethyl ethyl amine, dimethyl propyl amine, dimethyl 3-hydroxy-1 -propyl amine, dimethylbenzyl amine, dimethyl 2-hydroxy-1 -propyl amine, diethyl methyl amine, dimethyl 1 -hydroxy-2-propyl amine, pyridine, quinolone, and mixtures thereof. Other non-amine base catalysts reported include alkali metal hydroxides, alkali metal (Li, Na, K) salts of aliphatic carboxylic acids, such as acetic acid, propionic acid, methacrylic acid, acrylic acid, and the like.

While on the one hand these tertiary amines and alkali metal salts of carboxylic acids are good enough catalysts in effecting conversion to β-hydroxyl esters for industrial applications, the formation of greater or equal to 1 % of diesters and glycols can be detrimental for use in biomedical monomers and polymers.

Moreover, the siloxane (Si-O) bond in silicones is particularly susceptible to heterolytic scission in the presence of bases and can undergo re- equilibration reactions. Hence, this substantially negates the use of base catalysts in effecting the synthesis of β-hydroxyl esters using silicone epoxides or carboxylic acids because the siloxane backbone is significantly altered or degraded. Some of the rearrangement products are crosslinkers following the above reaction 5, specifically when the R substituent is a vinyl containing group.

Summary

Chromium (III) salts with organic acids are known as catalysts for facilitating epoxy-carboxylic acid reactions. Such Cr(lll) salts include simple

chromium(lll) tricarboxylate salts of fatty acids containing 1 -60 C atoms. The advantage of this catalyst is that it facilitates the epoxy-carboxylic acid reaction with minimal side-reactions of the etherification or disproportionation reactions described earlier.

Surprisingly, the formation of β-hydroxyl esters of silicones by the reaction of a silicone containing epoxide or carboxylic acid and an epoxide or carboxylic acid in the presence of a chromium (III) salt, such as a chromium (III) salt of carboxylic acid like chromium 2-ethyl-hexanoate, is possible without substantially rearranging or degrading the siloxane (Si-O) units of the silicone.

Disadvantageously, the resulting reaction crude is an undesirable green or blue color because of the presence of the chromium salt. Also, chromium is a heavy metal. As such, any health risks related to a significant amount of residual chromium remaining in the final products should be alleviated. This presents a limitation on the use of a Cr(lll) salt as a catalyst.

Further compounding this problem is that known distillation processes for the removal of residual chromium may not be available for high boiling point liquids. For example, certain poly(organo siloxanes), e.g. PDMS, containing liquids may possess a boiling point that is too high for known distillation processes.

Thus we have developed a process which makes possible the preparation of silicone containing β-hydroxyl esters without significant byproducts. Said process comprises:

a) forming a reaction product mixture by reacting a poly(organo siloxane) compound of formula 1

where Ri is an alkyl, vinyl, alkoxy group of linear, branched or cyclic structure or an aromatic group, having 1-20 C atoms,

R₂ and R₃ are each the same or different groups selected from alkyl, trialkylsiloxy, linear, branched or cyclic siloxane, alkoxy, alicyclic or aromatic groups,

R₄ is a divalent radical chosen from alkylene, polyether, perfluorinated polyether having up to 100 atoms,

n is an integer from 1-1000, and

A is a functional group that is either carboxylic acid or oxirane, with a compound of formula 2

where x is an integer from 0-18, where R₅ is H or an alkyl group having up to 18 C atoms, and

B is a functional group that is either an oxirane or a carboxylic acid, and wherein A and B are not both simultaneously oxirane or carboxylic acid, in the presence of a Cr(lll) salt,

b) contacting the reaction product mixture with amorphous silica and/or goethite, and

c) optionally repeating step b.

Detailed Description

The term "ethylenically unsaturated" refers to any groups that contains at least one C=C moiety. Some examples of such groups include, but not limited to, acryloyi, methacryloyl, allyl, vinyl, styrenyl, fumaryl, maleyl, crotonyl, itaconyl, cinnamyl acid, and 2,4-hexadecanoyl, etc.

The term "oxirane" or "epoxy" functionality represents a 1 ,2-epoxide of the structure:

The term "carboxylic acid" functionality represents the structure

Either the formula 3 or the formula 4 may represent A in formula 1 or B in formula 2. The /wv indicates the position where A or B is attached to the rest of the compounds according to formula 1 or 2. If A is an epoxy in formula 1 , then B is a carboxylic acid in formula 2. If A is a carboxylic acid in formula 1 , then B is an epoxy formula 2. The first step in the process is reacting a poly(organo siloxane) compound of formula 1 with a compound of formula 2 in the presence of a Cr(lll) organic salt.

Formula 1 represents the following poly(organo siloxane).

R-i is an alkyl, vinyl, or alkoxy group of linear, branched, cyclic or aromatic structure, having 1-20 C atoms. They include but are not limited to alkyl such as methyl, ethyl, propyl, butyl, pentyl and hexyl; aryl such as phenyl, tolyl and xylyl; aralkyl groups such as benzyl and phenethyl; and vinyl groups

In formula 1 , R₂ and R₃ are each independently selected from alkyl, trialkylsiloxy, cyclic or branched cyclic siloxane, alkoxy, alicyclic or aromatic groups . In embodiments, R₂ and R₃ are selected from a linear or branched alkyl group having 1 to 20 carbon atoms, a cycloalkyi group having 4 to 10 carbon atoms, or an aryl group or aryl-substituted hydrocarbon group having 6 to 10 carbon atoms.. A particularly preferred example of the polyorganosiloxane is a polydimethylsiloxane (R₂ and R₃ are both methyl).

Preferable examples of the linear or branched alkyl group having 1 to 20 carbon atoms include various functional groups such as methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl, t-butyl, pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, and dodecyl groups. Furthermore, preferable examples of the cycloalkyi group having 4 to 10 carbon atoms include various functional groups such as cyclopentyl and cyclohexyl. Preferable examples of the aryl group or aryl-substituted hydrocarbon group having 6 to 10 carbon atoms include various functional groups such as phenyl, toluyl, xylyl, ethylphenyl, benzyl, and phenethyl.

R₄ is a divalent radical chosen from alkylene, polyether, or

perfluorinated polyether. The alkylene divalent radical can be linear or branched containing 1-20 C atoms. They include but are not limited to alkylene such as methylene, ethylene, propylene, butylene, pentylene and hexylene radicals. The polyether radicals can include but are not limited to polyethylene glycol, polypropylene glycol, polybutylene glycol and their copolymers having up to 100 C atoms. The perfluorinated divalent radical can be linear or branched containing 1 -20 C atoms.

The method provides a simple and cost effective route for effecting the reaction between a silicone epoxide or carboxylic acid with a carboxylic acid or epoxide which can optionally contain silicone as well.

The Cr(lll) salt is an organic Cr(lll) salt. The Cr(lll) salt may be added as such, or may be formed in situ, for example, by using an organic acid and an inorganic Cr(lll) salt.

Examples of suitable Cr(lll) salts include but are not limited to chromium acetate hydroxide, chromium acetate, chromium propionate, chromium pentanoate, chromium butyrate, chromium 2-ethyl-hexanoate, chromium octoate, chromium decanoate, chromium oleate, chromium 2-octenoate, chromium toluate, chromium cresylate, chromium benzoate, chromium alkyl benzoates, chromium abietate, chromium naphthenates, chromium alkoxide, chromium acrylate, chromium methacrylate and the like.

The amount of Cr(lll) salt in the reaction mixture may vary. Typically, an amount between 0.05% and 5% relative to the total weight of the compounds according to formula (I) and (II) used, preferably an amount between 0.08% and 2.5%.

The reaction can be carried out neat and in the absence of any solvents. This is preferred, for cost and environmental reasons. Alternatively, the reaction can also be effected in the presence of solvents, such as e.g. hydrocarbons, ethers, esters, ketones, and the like.

In order to effect the reaction without the premature polymerization of the ethylenically unsaturated moieties, polymerization inhibitors are advantageously added to the reaction mixture, especially when the reaction is carried out at elevated temperatures. A number of suitable inhibitors are known in literature and can be chosen from monomethyl ether of hydroquinone, p-benzoquinone, t-butylcatechol, 4- hydroxy-2,2,6,6-tetramethylpiperidine 1 -oxyl and the like. The inhibitor may be added up to 20,000 ppm based on the total weight of the reaction product and preferably in amounts between 500 ppm and 20,000 ppm based on the total weight of the product.

Surprisingly, it has now been found that removal of Cr to an acceptable level can be obtained by contacting the reaction product mixture of a ring- opening addition reaction between an epoxide and a carboxylic acid using catalysts comprising a Cr(lll) salt with commercial amorphous silica or goethite. The amorphous silica may be a silica gel. The exact valency of the chromium present after reaction is unknown, and in fact is also irrelevant. Chromium, which may be Cr(lll) or in another form, is adsorbed on the amorphous silica or goethite surface, and thereby removed so that no or an acceptable amount remains. What an acceptable amount is, may be determined by law or by organizations that approve products before entrance on the market, for example the Food and Drug Administration in the USA (FDA). Typically, chromium will be removed to the extent that the amount remaining in the desired final product is less than 10 ppm, as measured independently by Proton Induced X-ray Emission (PIXE) elemental analysis and inductively coupled plasma mass

spectrometry (ICP-MS) without any preparative modification to the sample.

In an embodiment, the step of contacting the resulting reaction product mixture with amorphous silica or goethite is performed by amorphous silica or goethite mixed with the crude. In an embodiment, the step of contacting the resulting reaction product mixture with amorphous silica or goethite is performed by amorphous silica or goethite is performed with amorphous silica or goethite present in the form of a filter media.

The amorphous silica can be selected from natural and synthetic sources. Although synthetic silica is preferred over the natural sources, amorphous silica from a synthetic source is likely to contain no crystalline silica. This is preferred from a human health point-of-view (silicosis). The synthetic silica can be accessed commercially as precipitated or fumed silica having a pH at a 5 wt % concentration in water of 1 -14, more preferably between 4 and 10, and most preferably between 6 and 8. The BET surface area as determined with nitrogen of these amorphous silica may vary between wide ranges, and typically will be between 1 -500 m²/g. Some examples of the commercial amorphous silica include, but are not limited to, Davisil^® grades 710, 633, 635, 636, 643, 12, and Merck grade 10180, 10181 , 9385, 7734, 7754. The amorphous silica may be modified with functionalities such as amine, thiol, carboxylate salt, glycol and combinations thereof.

The resulting β-hydroxyl esters may be used as building blocks in the synthesis of polymers. As a result of the fact that the form β-hydroxyl esters according to the invention comprise less side reaction products, the polymers prepared using the β-hydroxyl esters may have different properties than known polymers.

The disclosed process may result in β-hydroxyl esters or products prepared therefrom that are suitable for use in medical applications, including medical coatings and/or implants. For example, β-hydroxyl esters obtained by the process may be used to produce silicone hydrogels. Silicone hydrogels find useful applications as biomedical materials, especially in the areas of contact lenses, wound care, etc.

In a preferred embodiment, the β-hydroxyl esters according to the invention comprise less than 10 ppm of chromium. This may be achieved by optimizing the pH of the purification process and/or by contacting the β-hydroxyl esters resulting from the process with silica and/or goethite a number of times. This can be done by repeatedly passing the β-hydroxyl esters over amorphous silica or goethite present in the form of a filter media.

The amount of Cr removal achieved by contacting with amorphous silica and/or goethite depends on the pH of the solution as well as the temperature of the process. The pH of the solution contacting the amorphous silica or goethite can preferably be between 3 and 12, more preferably between 5 and 10, and most preferably between 6 and 8. The temperature of the process can be between 0 and 60 °C and most preferably between 15 and 30 °C. The process is preferably carried out at atmospheric pressure (1 atm) or at elevated pressures of up to 100 psi.

In an embodiment, the method further comprises distilling off methyldi(trimethylsiloxy)sylylpropylglycerol methacrylate (SiGMA). SiGMA has the following formula 5:

The following examples illustrate embodiments of the claimed invention, but of course, should in no way be construed as limiting its scope. Examples

Example 1 :

67.33g of 3-(Glycidyloxypropyl)-1 ,1 ,1 ,3,5,5,5-heptamethyltrisiloxane (SE) (0.2 equivalents, eq) obtained from Gelest, Inc was reacted with 20.66g (0.24 eq of methacrylic acid) in the presence of 3 wt % Cr(lll) octoate (AMC2, AmPAC fine chemicals) catalyst and 0.09g polymerization inhibitor MeHQ at 90 °C overnight for 18h. The SE content was < 0.1 % as measured by gas chromatography analysis. The bottle green solution was diluted with 85g hexanes and excess methacrylic acid was extracted with a 0.4N wash of NaOH/2.5% NaCI solution. The raffinate was then further washed with 2.5% salt water until pH of the extract was neutral (6-8) as tested by pH paper.

The bottle green colored raffinate was dried over anhydrous sodium sulfate and contacted three times with 8 g amorphous silica followed by filtration to yield a clear colorless liquid. The hexanes was evaporated to yield the final product, SiGMA, as a clear, colorless liquid. The SiGMA yield was 96% yield with very low levels of dimethacrylate and glycol (<0.5%) as measured by gas chromatography analysis. Cr content was 4 ppm as measured by PIXE analysis.

Comparative Example 2:

67.33 g of SE obtained from Gelest, Inc was reacted with 20.66 g

(0.24 eq of methacrylic acid) in the presence of 0.3 wt % pyridine catalyst and 0.09 g polymerization inhibitor MeHQ at 75°C overnight for 26h it yielded a dark brown-black liquid. Gas chromatography analysis indicated 0% epoxide residual with significant amounts of lower retention time byproducts. The reaction was deemed degraded.

Comparative Example 2 demonstrates that the use of a pyridine catalyst does not result in the targeted product of SiGMA, and further purification of the reaction product was not possible.

Claims

A process for preparation of silicone containing β-hydroxyl ester comprising a) forming a reaction product mixture by reacting a poly(organo siloxane) compound of formula 1

(1 )

where Ri is an alkyl, vinyl, or alkoxy group of linear, branched, cyclic, or aromatic structure, having 1-20 C atoms,

R₂ and R₃ are each the same or different groups selected from alkyl, trialkylsiloxy, linear, branched, or cyclic siloxane, alkoxy, alicyclic or aromatic groups,

n is an integer from 1-1000, and

where x is an integer from 0-18,

where R₅ is H or an alkyl group having up to 18 C atoms, and

B is a functional group that is either an oxirane or a carboxylic acid, and wherein A and B are not both simultaneously oxirane or carboxylic acid, in the presence of a Cr(lll) salt, b) contacting the reaction product mixture with amorphous silica and/or goethite, and

c) optionally repeating step b.

2. The process according to claim 1 wherein the reaction between the compound of formula 1 and formula 2 is carried out in the presence of an inhibitor.

3. The process according to claims 1 or 2 wherein the Cr(lll) salt is selected from a carboxylate salt of Cr(lll).

4. The process according to any one of claims 1 -3 wherein said process is

conducted for a reaction time between about 1 and about 24 hours.

5. The process according to any one of claims 1 -3 wherein said process is

conducted for a reaction time between about 8 and about 18 hours.

6. The process according to any one of claims 1 -4, wherein step b) is carried out at a pH between 6 and 8.

7. The process according to any one of claims 1 -6, further comprising the step of distilling off methyldi(trimethylsiloxy)sylylpropylglycerol methacrylate.