WO1996014292A1

WO1996014292A1 - Process for the purification of a non-enolisable ester with a metallic reagent selected from a metal, a metal oxide or a metal hydride

Info

Publication number: WO1996014292A1
Application number: PCT/IE1995/000053
Authority: WO
Inventors: Valery Alexandrovich Dyatlov; Viktor Maleev; Tatiana Guseva
Original assignee: Saldane Limited
Priority date: 1994-11-04
Filing date: 1995-10-18
Publication date: 1996-05-17
Also published as: AU3753195A; IE940864A1

Abstract

A process for purification of non-enolisable esters, especially esters of 2-cyanoacrylic acid, from contaminating volatile acids, non-volatile acids and other substances which can decompose to generate strongly acidic impurities, comprises reacting a solution of the ester with a metallic reagent selected from a metal, metal oxide and a metal hydride or a mixture thereof in the form of a dispersion, emulsion or suspension. The metallic reagent is optionally supported on a solid, insoluble support. The process is especially suitable for the purification of liquid, non-distillable esters of 2-cyanoacrylic acid.

Description

PROCESS FOR THE PURIFICATION OF A NON-ENOLISABLE ESTER WITH A METALLIC REAGENT SELECTED FROM A METAL, A METAL OXIDE OR A METAL HYDRIDE

Technical Field

This invention relates to a process for the purification of esters, in particular, esters of 2-cyanoacrylic acid so that they can be obtained uncontaminated by acidic impurities, especially non-volatile acidic impurities.

Background Art

The ability of esters of 2-cyanoacrylic acid to polymerise rapidly (anionic polymerisation) under the influence of moisture or nucleophilic substances has led to their commercial exploitation as instantaneous adhesives. This polymerisation reaction is inhibited by acidic species and such inhibition may be partial or total. Partial inhibition leads to greatly increased setting times for the adhesive compositions with accompanying loss of industrial usefulness, and total inhibition leads to complete loss of adhesive properties. Very small (p.p.m.) amounts of acidic contaminants are able to cause inhibition of the anionic polymerisation process.

Several methods for the preparation of esters of 2-cyanoacrylic acid have been described. Patent Publication WO 94/15907 describes the synthesis of esters of 2-cyanoacrylic acid via its direct acid- catalysed esterification wherein a strong, usually non-volatile acid is used as catalyst. Patent Publication WO 94/15907 further describes the synthesis of esters of 2-cyanoacrylic acid via reaction of the derived 2- cyanoacryloyl chloride with, for example, an alcohol. In each instance, the esters of 2-cyanoacrylic acid which are formed may sometimes be contaminated by small amounts of acidic substances sufficient to inhibit their anionic polymerisation reaction to a greater or lesser degree. Such acidic substances may be derived inter alia from the strong acid catalyst mentioned supra, from side-reactions which take place during the preparation of intermediate 2-cyanoacryloyl chloride to give substances which may later release strong acids such as hydrochloric acid, or from residual unesterified 2-cyanoacrylic acid or 2-cyanoacryloyl chloride.

The extremely low level of acid contamination which can be tolerated when esters of 2-cyanoacrylic acid are to be utilised as instantaneous adhesives means that removal of such contamination is essential. In the case of distillable esters of 2-cyanoacrylic acid this can be achieved by distillation. However, few esters of 2-cyanoacrylic acid can be purified in this way as esters wherein the esterifying group contains more than about eight carbon atoms suffer decomposition at their boiling points even if the distillation is attempted at reduced pressure. A very large number of esters of 2-cyanoacrylic acid fall into this category. In the case of solid esters of 2-cyanoacrylic acid, recrystallisation may sometimes be used as a method for their purification. This is not always convenient as large volumes of solvent may be required. The use of basic substances for the removal of acidic contaminants from esters of 2-cyanoacrylic acid has not been utilised hitherto due to the instantaneous polymerisation reaction which these esters undergo upon their exposure to nucleophilic species.

Thus, a process for the removal of acidic contaminants, especially non-volatile acidic contaminants, from liquid, non-distillable esters of 2-cyanoacrylic acid has not yet been described.

However, a process for the removal of acidic contaminants, especially non-volatile acidic contaminants, from non-enolisable esters, generally and esters, including distillable and solid esters, of 2- cyanoacrylic acid in particular, is required which overcomes the aforementioned problems associated with known processes for their purification. 292 PCME95/00053

Disclosure of Invention

Accordingly, there is provided a process for the purification of non-enolisable esters from contaminating volatile acids, non-volatile acids and other substances which can decompose to generate strongly acidic impurities, which comprises reacting a solution of said ester with a metallic reagent selected from a metal, a metal oxide and a metal hydride or a mixture thereof in the form of a dispersion, emulsion or suspension, said metallic reagent optionally being supported on a solid, insoluble support.

By volatile acid herein is meant any acid which can be largely, but not completely, removed by sparging with an inert gas, by heating or by pumping under reduced pressure.

By non-volatile acid herein is meant any acid or polyacid which cannot be removed by sparging the reaction mixture with an inert gas under any reasonable conditions of temperature and pressure.

Examples of such non-volatile acids include, but are not limited to, alkyl- or arylsulfonic acids which may be employed as catalysts for the direct esterification of 2-cyanoacrylic acid. Further examples include, but are not limited to, phosphoric acid, polyphosphoric acid or halo- derivatives thereof which may be formed as by-products during the preparation of 2-cyanoacryloyl halides from 2-cyanoacrylic acid by reacting the latter with a phosphorus halide, especiaUy with phosphorus tri- or pentachloride to yield 2-cyanoacryloyl chloride. Additional examples of non-volatile acids include substances such as those indicated in formulae (I)-(V):

which may be formed from 2-cyanoacrylic acid as by-products during its conversion to 2-cyanocryloyl chloride by reaction with a phosphorus chloride.

Compounds of types (I)-(ffl) may, on storage, liberate hydrochloric acid. Compounds (IV) and (V) are capable of both releasing hydrochloric acid and of acting as strongly acidic inhibitors in their own right. Preferably, the ester is an ester of 2-cyanoacrylic acid, more especially a liquid, non-distillable ester.

The invention will be described hereinafter with particular reference to esters of 2-cyanoacrylic acid.

According to one aspect of the invention the metallic reagent used for removing contaminating acidic species from esters of 2- cyanoacrylic acid can be a suspension of a metal in an inert organic solvent and in the absence of a solid, insoluble support. The metal can be an alkali, alkaline earth or transition metal. Preferably, the metal is selected from lithium, sodium, potassium, calcium, aluminium and iron. The inert organic solvent is suitably any dry inert solvent, especially hexane, toluene or benzene.

For example, as is well known, finely-divided suspensions of potassium in benzene or of sodium in toluene can be prepared by melting these metals in boiling solvent, stirring vigorously to generate an emulsion, and then cooling the mixture to give the required suspension of solid metal.

In another aspect of the invention, the metallic reagent is a suspension of a metal oxide or of a metal hydride in an inert organic solvent which can be used to remove acidic contaminants from esters of 2-cyanoacrylic acid. The inert organic solvent is suitably any dry inert solvent, especially hexane, toluene or benzene. Suitably, the metal oxide is the dry oxide of an alkali, alkaline earth or other metal. Examples include, but are not limited to, magnesium oxide, calcium oxide and aluminium oxide.

Suitably, the metal hydride is the hydride of any alkali, alkaline earth or other metal, such hydride being unable to chemically reduce any unsaturated linkages present in said esters either in the carboxylic moiety or in the esterified radical. In a preferred embodiment of this aspect of the invention the metal hydride is calcium hydride. In a further aspect of the invention a solid, insoluble support is used to carry the metal, metal oxide or metal hydride or mixture thereof utilised to remove contaminating acidic impurities from esters. The support may take the form of either an inert or a reactive support.

By inert support herein is meant any supporting medium able to carry by adsorption a metal, metal oxide or metal hydride as defined supra, but which is unable to react with said metal, metal oxide or metal hydride.

By reactive support herein is meant a supporting medium which is able to react with the metal, metal oxide or metal hydride to form a new chemical species which then operates to remove the contaminating acidic impurities.

The choice of supporting medium depends upon the type of metal, metal oxide or metal hydride which is being used. Typical supports include, but are not limited to, powdered charcoal, aluminium oxide, silicon oxide and aluminosilicates. Some of these supports may behave either as inert or as reactive supports depending upon the nature of the metal, metal oxide or metal hydride which is adsorbed thereon. For example, charcoal behaves as an inert support towards iron oxide but as a reactive support towards potassium with which it forms an inclusion compound. A metal oxide can be utilised as a reactive support. For example, calcium oxide can be treated with a limited amount of sodium metal to provide via a metathesis reaction calcium oxide carrying a mixture of sodium oxide and calcium metal. Thus, a solid support may be freed from residual moisture and then loaded with a metal, a metal oxide, a metal hydride or a mixture of metal(s) and metal oxide(s).

Optionally, the metal is applied to the surface of the support by chemical reduction of a metal oxide which forms the support or which has been applied to the surface thereof. Layers of metal oxides can be applied to the surface of a support by thermal breakdown of an appropriate salt adsorbed thereon. For example, a layer of iron oxide can be deposited on powdered aluminium oxide by coating the latter with iron nitrate and then heating the product.

The ester to be purified according to the invention may be dissolved in an inert organic solvent such as hexane, benzene or toluene. Alternatively, esters prepared in such solvents by the acid- catalysed esterification of a carboxylic acid or by reaction of an acyl halide with an alcohol or phenol can be purified in solution without evaporation of the solvent and intermediate isolation of contaminated ester. These solutions may optionally contain a stabiliser which inhibits the anionic polymerisation, a stabiliser which inhibits the free-radical polymerisation or a mixture of such stabilisers. However, the presence of a stabiliser is not essential.

When esters of 2-cyanoacrylic acid are to be purified according to the process of the invention the presence of a mixture of stabilisers which inhibit anionic and free-radical polymerisation reactions is preferred. These inhibitors must themselves be stable under the conditions of the purification process. The most preferred types of anionic polymerisation inhibitors are sulfonic acid esters, and the most preferred types of free-radical polymerisation inhibitors are appropriately substituted esters of 2-cyanoacrylic acid. By appropriately substituted ester in this context is meant a substituted ester effective to achieve the requisite inhibition.

The purification step according to the invention is carried out by vigorously mixing a solution of the ester to be freed from acidic contaminants with an emulsion, suspension or dispersion of one of the metallic reagents hereinabove described.

Suitable inhibitors of anionic and free-radical polymerisation reactions may first be added to the solution when polymerisable esters such as esters of 2-cyanoacrylic acid are to be purified.

Preferably, the mixture is sparged with a dry inert gas such as nitrogen, argon or helium before and during the purification process in order to remove any volatile acids which may be present. The temperature at which the purification process is carried out depends upon the nature of the ester to be purified, the solvent used, and the nature of the metallic reagent used. The process according to the invention can be carried out at temperatures between -20°C and 150°C, preferably between +20°C and 110°C. The purification of esters containing chemical functionality which is prone to free-radical polymerisation can be carried out at 20°C-40°C in order to prevent thermally-induced free-radical polymerisation reactions from taking place. When thermally stable esters are being purified by the process according to the invention wherein an alkali metal such as sodium is the metallic reagent then it is preferable to conduct the process at a temperature higher than the melting point of the metal, so that an emulsion of molten metal is present.

The duration of the purification process according to the invention depends upon the level of acid contamination initially present in the ester, the temperature at which the purification is carried out, and the nature of the metallic reagent used for purification.

Initial sparging with an inert gas as described supra removes much of any volatile acid contamination which may be present, and this reduces the time needed to complete the purification process.

In the case of esters of 2-cyanoacrylic acid which polymerise by the anionic polymerisation process, the progress of the purification reaction can be monitored by measuring the setting time of the isolated ester needed to give a satisfactory adhesive bond.

The isolation of purified ester from the reaction mixture is preferably carried out by cooling to ambient temperature, removal of the metallic reagent by filtration or centrifugation, and evaporation of the solvent under polymerisation-inhibiting conditions.

For liquid esters of 2-cyanoacrylic acid, anionic polymerisation can be inhibited by the addition of non-volatile stabilisers additional to any which may have been present during the purification process, by the addition of volatile stabilisers, or by the addition of a mixture of volatile and non- volatile stabilisers. Suitable non- volatile anionic polymerisation inhibitors are 3-hydroxypropanesulfonic acid, methanesulfonic acid or sulfonic acid esters such as γ-propanesultone. Suitable volatile anionic polymerisation inhibitors are carbon dioxide and sulfur dioxide. Free-radical polymerisation reactions are preferably inhibited by the addition of suitable amounts of hydroquinone.

Modes for Carrying Out the Invention

The invention is further illustrated by the following Examples.

Example 1

Preparation of a suspension of aluminium in an inert solvent

A suspension of aluminium powder in mineral oil or wax was stirred with hot benzene or hot toluene and then collected by filtration under a dry inert atmosphere. The washing process was repeated four times to ensure complete removal of mineral oil or wax, and the metal powder was then resuspended in fresh benzene or toluene.

Example 2

Preparation of a suspension of sodium in toluene

A 500 ml flask provided with a mechanical stirrer, an inlet for dry nitrogen, and a reflux condenser was charged with 200 ml of dry toluene and 2 g of sodium. The mixture was heated to reflux with vigorous stirring and continuous sparging with nitrogen to give an emulsion of molten sodium in toluene. This was then cooled with continuous vigorous stirring to yield a finely-divided suspension of sodium in toluene. Example 3

Preparation of sodium on aluminium oxide

Powdered aluminium oxide (8 g) was dried by heating at 600°C under an inert atmosphere during 4 hours. Towards the end of this time a stream of hydrogen chloride gas was passed over the oxide to remove residual surface moisture. The adsorbent was cooled to 110°C and placed in a 150 ml flask provided with a mechanical stirrer and an inlet for dry argon. Sodium (0.5 g) was added and the mixture was stirred to yield a gray coating of sodium on the inert finely divided aluminium oxide support.

Example 4

Preparation of a mixture of metallic sodium and aluminium oxide

A 500 ml flask was provided with a mechanical stirrer, and inlet for dry argon and a condenser arranged for distillation, and was charged with 8 g of aluminium oxide and 350 ml of dry toluene. The mixture was heated and 100 ml of a toluene- water azeotrope was distilled off. The condenser was then arranged for reflux and 1 g of sodium was added with continuous sparging of argon. The mixture was stirred at reflux during 2 hours and then cooled with continuous stirring to give a mixture of metallic sodium and aluminium oxide suspended in toluene.

Example 5

Synthesis of the Z? -?-cvanoacrylate ester of diethylene glycol

10.85 g of 2-Cyanoacrylic acid was dissolved in 250 ml of hot dry toluene containing 2 mg of γ-propanesultone. The solution was charged into a 500 ml flask provided with a mechanical stirrer, dropping funnel, argon inlet and condenser arranged for distillation, and was cooled to 40°C. A solution of 23.3 g (111.9 mmol) of phosphorus pentachloride in 150 ml of dry toluene was added drop wise with stirring and sparging with argon. 200 ml of toluene and by¬ product phosphorus oxychloride were then distilled off to leave 200 ml of a colourless transparent solution of impure 2-cyanoacryloyl chloride in toluene.

A 500 ml flask provided with a mechanical stirrer, an inlet for argon and a condenser arranged for distillation was charged with 200 ml of toluene containing 111.9 mmol of 2-cyanoacryloyl chloride prepared from 10.85 g of 2-cyanoacrylic acid as described supra. This was heated to 45°C and a solution of 5.39 g (55.9 mmol) of diethylene glycol in 150 ml of dry toluene was added dropwise with stirring and sparging of argon. The mixture was stirred at room temperature during a further 1.5 hours, and 250 ml of solvent was then distilled off to give 150 ml of a colourless solution containing 15 g of the bis- cyanoacrylate ester of diethylene glycol. H NMR spectrum in 3:1 toluene/C₆D₆ 3.22 (4H, m, -C//₂OC//₂-), 3.47 (4H, m, 2 <2> -C ₂OC(0)-), and 5.57 and 6.36 (2s, each 2H, 2 @ H₂C=C-) p.p.m.

Example 6

Synthesis of the fr/s-cvanoacrylate ester of 1.3-fa^'j-(3- hvdroxypropyDtetramethyldisiloxane

A 300 ml flask provided with a mechanical stirrer, an inlet for argon and a condenser arranged for distillation was charged with 100 ml of a solution of 10.4 mmol of 2-cyanoacryloyl chloride in toluene obtained from 1 g of 2-cyanoacrylic acid as described in Example 5 supra. The mixture was brought to reflux and a solution of 1.25 g

(4.99 mmol) of l,3-ύ«-(3-hydroxypropyl)tetramethyldisiloxane in 150 ml of dry benzene was added dropwise with constant stirring, sparging of argon and distillation of solvent. After 150 ml of solvent had been distilled off there was left 75 ml of a colourless solution containing 2.1 g of the few-cyanoacrylate ester of l,3-to(3-hydroxypropyl)- tetramethyldisiloxane in a toluene-benzene mixture. H NMR spectrum in 3:1 toluene/C₆D₆ -0.002 (12H, s, C ^Si groups), 0.388 (4H, m, -C/ ₂SiO- groups), 1.536 (4H, m, -CH₂C ₂CH₂- groups), 4.397 (4H, t, J 8 Hz, -C/ ₂OC(0)- groups), and 5.77 and 6.44 (2s, each 2H, 2 @ / C=C-) p.p.m.

Example 7

Synthesis of the fr s-cvanoacrylate ester of 1.3-bis-(4- hydroxybutyDtetramethyldisiloxane

A 300 ml flask provided with a mechanical stirrer, an inlet for argon and a condenser arranged for distillation was charged with 100 ml of a solution of 10.4 mmol of 2-cyanoacryloyl chloride obtained from 1 g of 2-cyanoacrylic acid as described in Example 5 supra. The mixture was brought to reflux and a solution containing 30 mg of hydroquinone and 1.4 g (5.02 mmol) of l,3-dw-(4-hydroxybutyl)- tetramethyldisiloxane in 150 ml of dry toluene was added dropwise with constant stirring, sparging with argon and distillation of solvent. The mixture was stirred, while 175 ml of solvent was removed by distillation to give 75 ml of a colourless solution containing 2.25 g of the 6 5-cyanoacrylate ester of l,3-6/$-(4-hydroxybutyl)- tetramethyldisiloxane in toluene.

Example 8

Synthesis of the fr/.s-cvanoacrylate ester of triethylene glycol

A 500 ml flask provided with a mechanical stirrer, an argon inlet and a condenser arranged for distillation was charged with 175 ml of a solution of 52.5 mmol of 2-cyanoacryloyl chloride in toluene obtained from 5.12 g of 2-cyanoacrylic acid as described in Example 5 supra. A solution of 3.9 g (26 mmol) of triethylene glycol and 1 mg of γ- propanesultone in 250 ml of hot dry toluene was added dropwise at 50°C-55°C with continuous stirring and sparging of argon. The mixture was stirred at 45°C during a further 2.5 hours, and 250 ml of solvent was then distilled off in vacuo at 70°C to give 175 ml of a colourless solution containing 8 g of the 6/->-cyanoacrylate ester of triethylene glycol in toluene. A further 1 mg of γ-propanesultone was added to this solution. ^lH NMR spectrum in 3:1 toluene/C_όD_ό 3.36 (8H, m, -CH₂OCH₂CH₂OCH₂-), 4.07 (4H, m, -C ₂OC(0)- groups), and 5.55 and 6.34 (2s, each 2H, ₂C=C-) p.p.m.

Example 9

Synthesis of the cyanoacrylate ester of 2-hvdroxyethyl methacrylate

A 500 ml flask provided with a mechanical stirrer, an argon inlet and a condenser arranged for vacuum distillation was charged with 175 ml of a solution of 48.7 mmol of 2-cyanoacryloyl chloride in toluene obtained from 4.75 g of 2-cyanoacrylic acid as outlined in Example 5 supra. A solution of 6.37 g (48.97 mmol) of 2-hydroxyethyl methacrylate, 1 mg of γ-propanesultone and 1 mg of (1,1,3 - trihydro)tetrafluoropropyl 2-furfurylidene-2-cyanoacetate in 75 ml of dry toluene was added dropwise with stirring and sparging of argon at 35°C. The mixture was stirred at 40°C during 1.5 hours and 100 ml of solvent was then distilled off at that temperature in vacuo to give 150 ml of a colourless solution of the cyanoacrylate ester of 2-hydroxyethyl methacrylate in toluene. A further 1 mg of γ-propanesultone and 1 mg of (l,l,3-trihydro)tetrafluoropropyl 2-furfurylidene-2-cyanoacetate were added to this solution. H NMR spectrum in 3:1 toluene/CόDό 1.76 (3H, dd, Jγ 1.5 Hz, J₂ 1.0 Hz, C /₃C=C-), 3.84 (4H, m, - OC ₂C//₂0-), 5.16 and 6.05 (2s, each 1H, C//₂=C(CH₃)-), and 5.35 and 6.14 (2s, each 1H, C//₂=C(CN)-) p.p.m.

Example 10

Purification of a thermally stable ester using an emulsion of sodium metal in an inert solvent and in the absence of polymerisation inhibitors

200 ml of a suspension of finely divided sodium in toluene prepared as described in Example 2 supra was shaken during 2 minutes to ensure complete suspension of the metal, and 50 ml of this suspension was added to 75 ml of a solution of the 6 j-cyanoacrylate of l,3-bis-(3-hydroxypropyl)tetramethyldisiloxane prepared according to Example 6 supra. The resulting mixture was heated at reflux with constant stirring and sparging of argon during 8 hours. About 100 ml of solvent was then distilled off and the suspension was filtered to yield 75 ml of a colourless transparent solution. The remaining solvent was distilled off in vacuo while sparging with sulfur dioxide to give 2.1 g of the liquid ^-cyanoacrylate ester of l,3-bis-(3-hydroxypropyl)- tetramethyldisiloxane saturated with sulfur dioxide. 0.01 mg of γ- propanesultone was added using a dilute stock solution in benzene, and residual solvent was evaporated in vacuo to give 1.9 g of the pure stabilised /$-cyanoacrylate ester. *H NMR C₆D₆ -0.002 (12H, s,

C ₃Si groups), 0.388 (4H, m, -C ₂SiO- groups), 1.536 (4H, m, -CH₂C/ ₂CH₂- groups), 4.397(4H, t, / 8 Hz, -C ₂OC(0)- groups), and 5.77 and 6.44 (2s, each 2H, 2 @ // C=C-) p.p.m.

Example 11

Purification of a thermally stable ester using sodium on aluminium oxide and in the absence of polymerisation inhibitors

0.5 g of finely divided sodium on aluminium oxide prepared as described in Example 3 supra was added to 75 ml of the toluene solution of the ^ .-'-cyanoacrylate ester of 1 ,3-6/.y-(4-hydroxybutyl)- tetramethyldisiloxane prepared as described in Example 7 supra. 100 ml of dry toluene was added to the mixture which was then heated at reflux with stirring and constant sparging of argon during 2 hours. 100 ml of solvent was then distilled off and the suspension was filtered to give 75 ml of a colourless transparent solution. The remaining solvent was distilled off in vacuo with sparging by sulfur dioxide to give 2.3 g of the liquid ό j-cyanoacrylate ester of l,3-bis-(4- hydroxybutyl)tetramethyldisiloxane saturated with sulfur dioxide. 0.01 mg of γ-propanesultone was added using a stock solution in benzene and residual solvent was evaporated in vacuo to give 2.0 g of the pure ester stabilised with γ-propanesultone. Example 12

Purification of a thermally stable ester using a mixture of metallic sodium and aluminium oxide and in the presence of a free-radical polymerisation inhibitor

250 ml of a suspension of a mixture of sodium and aluminium oxide prepared as described in Example 4 supra was shaken during 2 minutes to ensure complete suspension and then 50 ml of this mixture was added to 150 ml of a solution of the fcw-cyanoacrylate ester of diethyleneglycol prepared as described in Example 5 supra. 1 mg of ethyl 2-furfurylidene-2-cyanoacetate was added and the mixture was heated to boiling for 5 hours during which time there was constant stirring, sparging of argon and slow distillation of 100 ml of solvent. The resulting gray suspension was filtered to yield a colourless transparent solution from which solvent was distilled off in vacuo with sparging of sulfur dioxide to give 12 g of the liquid ft j-cyanoacrylate ester of diethyleneglycol saturated with sulfur dioxide. 0.01 mg of γ- propanesultone was added to give 11.2 g of the pure ester stabilised with γ-propanesultone. H NMR spectrum in C^O^ 3.34 (4H, m, - C ₂OC//₂-), 3.06 (4H, m, 2 @ -C /₂OC(0)-), and 6.02 and 6.55 (2s, each 2H, / ₂C=C-)p.p.m.

Example 13

Purification of a thermally stable ester using a metal hydride in the presence of a free-radical polymerisation inhibitor

0.5 g of calcium hydride was added to 175 ml of a solution of the ft/j-cyanoacrylate ester of triethyleneglycol prepared as described in Example 8 supra. 2 mg of pyrogallol was added and the mixture was heated under reflux during 5 hours with stirring and constant sparging of argon. 100 ml of toluene was distilled off to give 75 ml of a white suspension. This was filtered to yield a colourless transparent solution. Solvent was distilled off in vacuo with sparging of sulfur dioxide to give 8 g of the liquid

ester of triethyleneglycol saturated with sulfur dioxide. 0.01 mg of γ-propanesultone was added using a stock solution in benzene and residual solvent was evaporated in vacuo to give 7.2 g of the pure ester stabilised with γ-propanesultone. ^lH NMR spectrum in C₆D₆ 3.30 (8H, m, -C ₂OC /₂C ₂OC//₂-), 4.05 (4H, m, -C/ OC(0)- groups), and 5.57 and 6.32 (2s, each 2H, ₂C=C-)p.p.m.

Example 14

Purification of a thermally unstable ester using a mixture of two metals and a metal oxide and in the presence of a free-radical polymerisation inhibitor and an anionic polymerisation inhibitor

1 g of a dispersion of a reagent prepared from 0.25 g of sodium, 0.25 g of calcium and 0.5 g of calcium oxide was added to 150 ml of a solution of the 2-cyanoacrylate ester of 2-hydroxyethyl methacrylate prepared as described in Example 9 supra. The mixture was heated at 45°C-50°C for 8 hours with stirring and sparging of argon. 50 ml of toluene was then distilled off in vacuo at 45°C with sparging of sulfur dioxide to give 100 ml of a gray suspension. This was filtered to give a colourless transparent solution. 0.1 mg of ethyl 2-furfurylidene- cyanoacetate was added and the solvent was distilled off in vacuo with sparging of sulfur dioxide to give 10 g of the liquid cyanoacrylate ester of 2-hydroxyethyl methacrylate saturated with sulfur dioxide. 0.01 mg of γ-propanesultone was added using a stock solution in benzene and residual solvent was evaporated in vacuo to give 8.9 g of pure ester stabilised with γ-propanesultone. *H NMR spectrum in CgDg 1.79 (3H, dd, J_λ 1.5 Hz, J₂ 1 Hz, C//₃C=C-), 3.93 (4H, m, -OC ₂C ₂)-), 5.21 and 6.09 (2s, each 1H, / ₂C=C(CH₃)-), and 5.52 and 6.24 (2s, each 1H, / ₂C=C(CN)-) p.p.m.

Example 15

A suspension of aluminium powder (0.6 g) in dry toluene prepared as described in Example 1 supra was added to 175 ml of a solution of the WaV-cyanoacrylate ester of triethyleneglycol prepared as described in Example 8 supra. The resulting mixture was heated under reflux during 8 hours with constant stirring and constant sparging of dry argon. 100 ml of toluene was distilled off to give 75 ml of a gray suspension. This was filtered to give a colourless transparent solution. The remaining toluene was distilled off in vacuo with constant sparging of sulfur dioxide to give 8.2 g of the liquid ft/j-cyanoacrylate ester of triethyleneglycol saturated with sulfur dioxide. 0.01 mg of γ- propanesultone was added using a stock solution in benzene and residual solvent was evaporated in vacuo to give 7.5 g of the pure bis- cyanoacrylate ester of triethyleneglycol stabilised with γ- propanesultone. H NMR spectrum in C ^ 3.30 (8H, m, -C ₂OC /₂CH₂OC /₂-), 4.05 (4H, m, -C /₂OC(0)- groups), and 5.57 and 6.32 (2s, each 2H, C=C-)p.p.m.

Example 16

Estimation of the amount of residual acidic contaminants in 2- cvanoacrylate esters purified according to the process of the invention

Estimation of the amount of residual acidic contamination, if any, in 2 -cyanoacrylate esters purified according to the process of the invention was carried out by measuring the setting time of an adhesive composition prepared from the ester under test. The levels of residual acidic contamination are too low to permit the use of traditional chemical methods for their measurement. In effect, what is measured is the setting time of a standard sample of the well-known instantaneous adhesive ethyl 2-cyanoacrylate versus its setting time as an admixture with 10% w/w of the cyanoacrylate ester under test. It is known that if standard ethyl 2-cyanoacrylate contains more than 50 p.p.m. of residual acidic contaminants then the time needed to form a satisfactory adhesive bond between two prepared steel lap shears is greater than 10 minutes.

100 ± 1 mg of the cyanoacrylate ester to be tested was placed in a polyethylene bottle and 900 ± 1 mg of commercial ethyl 2- cyanoacrylate Sicomet (Sicomet is a trade mark) having a setting time of 1 minute in the lap shear test was added. The mixture was stirred well to ensure complete solution and the resulting adhesive composition was used to bond prepared steel lap shears. The setting time necessary to achieve satisfactory bonding was measured and the results for a series of esters are presented in the following Table.

Table

Sample Ester Purification Setting time as in Example method as in supra Example supra

1 6 10 5 mins

2 7 11 5 mins

3 5 12 2.5 mins

4 8 13 3.5 mins

5 9 14 4.5 mins

6 8 15 5 mins

7 8 none > 480 mins

8 9 none > 480 mins

Claims

Claims: -

1. A process for the purification of non-enolisable esters from contaminating volatile acids, non-volatile acids and other substances which can decompose to generate strongly acidic impurities, which process comprises reacting a solution of said ester with a metallic reagent selected from a metal, a metal oxide and a metal hydride or a mixture thereof in the form of a dispersion, emulsion or suspension, said metallic reagent optionally being supported on a solid, insoluble support.

2. A process according to Claim 1, wherein the ester is an ester of 2-cyanoacrylic acid.

3. A process according to Claim 2, wherein the ester is a liquid, non-distillable ester.

4. A process according to any preceding claim, wherein the metallic reagent is a suspension of a metal in an inert organic solvent in the absence of a solid, insoluble support.

5. A process according to Claim 4, wherein the metal is an alkali, alkaline earth or transition metal.

6. A process according to Claim 5, wherein the metal is selected from lithium, sodium, potassium, calcium, aluminium and iron.

7. A process according to any one of Claims 1-3, wherein the metallic reagent is a suspension of a metal oxide or a metal hydride in an inert organic solvent.

8. A process according to Claim 7, wherein the metal oxide is a dry oxide of an alkali, alkaline earth or other metal.

9. A process according to Claim 8, wherein the metal oxide is magnesium oxide, calcium oxide or aluminium oxide.

10. A process according to Claim 7, wherein the metal hydride is the hydride of an alkali, alkaline earth or other metal, said hydride being unable to chemically reduce any unsaturated linkages present in said esters either in the carboxylic moiety or in the esterified radical.

11. A process according to Claim 9 or 10, wherein the metal hydride is calcium hydride.

12. A process according to any one of Claims 4-11, wherein the inert organic solvent is a dry inert organic solvent selected from hexane, toluene and benzene.

13. A process according to any preceding claim, wherein a solid, insoluble support is used to carry the metal, metal oxide or metal hydride or mixture thereof.

14. A process according to Claim 13, wherein the support is an inert support.

15. A process according to Claim 13, wherein the support is a reactive support.

16. A process according to any one of Claims 13-15, wherein the metal is applied to the surface of the support by chemical reduction of a metal oxide which forms the support or which has been applied to the surface thereof.

17. A process according to any preceding claim, wherein the ester to be purified is dissolved in an inert organic solvent.

18. A process according to any preceding claim, which is carried out in the presence of an inhibitor of anionic polymerisation.

19. A process according to Claim 18, wherein the inhibitor of anionic polymerisation is a sulfonic acid ester.

20. A process according to any preceding claim, which is carried out in the presence of an inhibitor of free-radical polymerisation.

21. A process according to Claim 20, wherein the inhibitor of free-radical polymerisation is a substituted ester of 2-cyanoacrylic acid effective to achieve such inhibition.

22. A process according to Claim 21, wherein the inhibitor is ethyl 2-furfurylidene-2-cyanoacetate.

23. A process according to any preceding claim, wherein the mixture is sparged with a dry inert gas before and during the purification process so as to remove any volatile acids present.

24. A process according to any preceding claim, which is carried out at a temperature in the range -20°C-150°C.

25. A process according to any preceding claim, which is carried out at a temperature in the range 20°C-40°C in order to prevent thermally induced free-radical polymerisation reactions.

26. A process according to any preceding claim, wherein the purified ester is isolated from the reaction mixture by cooling to ambient temperature, removal of the metallic reagent and evaporation of the solvent under polymerisation-inhibiting conditions.

27. A process according to any one of Claims 3-26, wherein anionic polymerisation is inhibited solely or additionally by a non- volatile stabiliser, a volatile stabiliser or a mixture thereof.

28. A process according to Claim 27, wherein when a non¬ volatile anionic polymerisation inhibitor is used, the inhibitor is selected from 3-hydroxypropanesulfonic acid, methanesulfonic acid and a sulfonic acid ester.

29. A process according to Claim 27 or 28, wherein a volatile inhibitor of anionic polymerisation is used and is selected from carbon dioxide and sulfur dioxide.

AMENDED CLAIMS

[received by the International Bureau on 9 Apri l 1996 (09.04.96) ; original claim 2 cancelled; original claims 3-29 renumbered as claims 2-28 (4 pages) ]

1. A process for the purification of non-enolisable esters of 2-cyanoacrylic acid from contaminating volatile acids, non-volatile acids and other substances which can decompose to generate strongly acidic impurities, which process comprises reacting a solution of said ester with a metallic reagent selected from a metal, a metal oxide and a metal hydride or a mixture thereof in the form of a dispersion, emulsion or suspension, said metallic reagent optionally being supported on a solid, insoluble support.

2. A process according to Claim 1, wherein the ester is a liquid, non-distillable ester.

3. A process according to any Claim 1 or 2, wherein the metallic reagent is a suspension of a metal in an inert organic solvent in the absence of a solid, insoluble support.

4. A process according to Claim 3, wherein the metal is an alkali, alkaline earth or transition metal.

5. A process according to Claim 4, wherein the metal is selected from lithium, sodium, potassium, calcium, aluminium and iron.

6. A process according to Claim 1 or 2, wherein the metallic reagent is a suspension of a metal oxide or a metal hydride in an inert organic solvent.

7. A process according to Claim 6, wherein the metal oxide is a dry oxide of an alkali, alkaline earth or other metal.

8. A process according to Claim 7, wherein the metal oxide is magnesium oxide, calcium oxide or aluminium oxide. 9. A process according to Claim 6, wherein the metal hydride is the hydride of an alkali, alkaline earth or other metal, said hydride being unable to chemically reduce any unsaturated linkages present in said esters either in the carboxylic moiety or in the esterified radical.

10. A process according to Claim 8 or 9, wherein the metal hydride is calcium hydride.

11. A process according to any one of Claims 3-10, wherein the inert organic solvent is a dry inert organic solvent selected from hexane, toluene and benzene.

12. A process according to any preceding claim, wherein a solid, insoluble support is used to carry the metal, metal oxide or metal hydride or mixture thereof.

13. A process according to Claim 12, wherein the support is an inert support.

14. A process according to Claim 12, wherein the support is a reactive support.

15. A process according to any one of Claims 12-14, wherein the metal is applied to the surface of the support by chemical reduction of a metal oxide which forms the support or which has been applied to the surface thereof.

16. A process according to any preceding claim, wherein the ester to be purified is dissolved in an inert organic solvent.

17. A process according to any preceding claim, which is carried out in the presence of an inhibitor of anionic polymerisation.

18. A process according to Claim 17, wherein the inhibitor of anionic polymerisation is a sulfonic acid ester. 19. A process according to any preceding claim, which is carried out in the presence of an inhibitor of free-radical polymerisation.

20. A process according to Claim 19, wherein the inhibitor of free-radical polymerisation is a substituted ester of 2-cyanoacrylic acid effective to achieve such inhibition.

21. A process according to Claim 20, wherein the inhibitor is ethyl 2-furfurylidene-2-cyanoacetate.

22. A process according to any preceding claim, wherein the mixture is sparged with a dry inert gas before and during the purification process so as to remove any volatile acids present.

23. A process according to any preceding claim, which is carried out at a temperature in the range -20°C-150°C.

24. A process according to any preceding claim, which is carried out at a temperature in the range 20°C-40°C in order to prevent thermally induced free-radical polymerisation reactions.

25. A process according to any preceding claim, wherein the purified ester is isolated from the reaction mixture by cooling to ambient temperature, removal of the metallic reagent and evaporation of the solvent under polymerisation-inhibiting conditions.

26. A process according to any one of Claims 2-25, wherein anionic polymerisation is inhibited solely or additionally by a non¬ volatile stabiliser, a volatile stabiliser or a mixture thereof.

27. A process according to Claim 26, wherein when a non- volatile anionic polymerisation inhibitor is used, the inhibitor is selected from 3-hydroxypropanesulfonic acid, methanesulfonic acid and a sulfonic acid ester. 28. A process according to Claim 26 or 27, wherein a volatile inhibitor of anionic polymerisation is used and is selected from carbon dioxide and sulfur dioxide.