IE930599A1 - Process for the preparation of esters of 2-cyanoacrylic acid¹and use of the esters so prepared - Google Patents

Abstract

A process for the preparation of esters, including non-distillable esters, of 2-cyanoacrylic acid comprises reacting 2-cyanoacrylic acid or an acid halide thereof with an alcohol, including a diol or polyol, or a phenol in the presence of an inert organic solvent under polymerisation inhibiting conditions and, additionally, in the presence of an acid catalyst when 2-cyanoacrylic acid is a reactant, continually removing the water or hydrohalous acid produced and recovering the ester. The esters thereby prepared include substituted or unsubstituted long chain alkyl cyanoacrylates and multifunctional cyanoacrylates, including bis cyanoacrylates. Such esters have a wide range of applications. For example, they can be grafted onto polymer backbones to improve properties of said polymers such as thermal resistance.

Description

Process for the preparation of esters of 2-cyanoacrvlic acid and use of the esters so prepared This invention relates to a process for the preparation of esters of 2-cyanoacrylic acid, including long chain esters, and the use of the esters so prepared.

Cyanoacrylate esters are the main constituent of instant or rapid bonding adhesives, commonly known as 'superglues'. Bonding in the case of such adhesives results from the conversion of a low viscosity liquid to a solid polymer by anionic polymerisation. Cyanoacrylate esters are also used for the manufacture of polyalkylcyanoacrylate nanoparticles and nanocapsules used as drug and other active agent carrier systems.

Until now, the only commercial route for the preparation of cyanoacrylate esters was the Knoevangel Condensation Method (H. Lee.

(Ed.) (1981) Cyanoacrylic Resins - The Instant Adhesives, Pasadena Technology Press, Pasadena, U.S.A.). According to the Knoevangel method cyanoacetate and formaldehyde are reacted together in the presence of an amine to give oligomers of polyalkylcyanoacrylates.

The free cyanoacrylate monomer is generated by thermally cracking the oligomer under vacuum and distilling onto anionic acid stabiliser under vacuum. Following the distillation step, a free radical stabiliser, such as methylhydroquinone, may be added to inhibit free radical polymerisation during storage. Free radical polymerisation can be initiated, for example, by exposure to light.

The Knoevangel method is limited to the preparation of alkyl cyanoacrylates which have an alkyl moiety with no more than ten carbon atoms. Above ten carbon atoms, the monomers cease to be distillable at temperatures below their respective thermal destruction temperatures. In fact, n-octyl cyanoacrylate is the monomer with the greatest number of carbon atoms that has been reported in the literature to have been prepared by the Knoevangel method and has been used in the preparation of a medical adhesive (Kublin, K.S. and CdF7 /33/ L Miguel, F.M., (1970) J. Amer. Vet. Med. Ass. Vol. 156, No. 3, p.3138 and Alco, J.J. and DeRenzis, F.A., (1971) J. Pharmacol. Ther. Dent. Vol. 1, No. 3, p. 129-32).

Short chain (less than ten carbon atoms) alkyl cyanoacrylates 5 with polar groups such as hydroxyl, carboxyl and ester groups and aryl cyanoacrylates cannot generally be prepared by the Knoevangel Condensation Method because of their high boiling points.

Additionally, multifunctional cyanoacrylates, such as bis cyanoacrylates, cannot be synthesised because they are non-distillable below their thermal destruction temperatures.

A method for the preparation of bis cyanoacrylates, which are indicated to be useful as thermally and moisture resistant acrylate additives are the subject of U.S. Patent No. 3,903,055. The method can involve essentially three or five steps. In the five-step method, ethyl or isobutyl cyanoacrylate is reacted with anthracene to form its stable Diels-Alder anthracene adduct. Basic hydrolysis of the adduct gives the corresponding acid salt from which the corresponding acid is obtained upon acidification. The carboxylic acid is then converted to its acid chloride with thionyl chloride and then reacted with diol to give the bis anthracene diester. Displacement of the adduct by the stronger dienophile maleic anhydride gives bis cyanoacrylates in good yield. However, this multi-step method is purely a laboratory method and scaling up to a commercially viable level has not proved practicable.

To date, the method of U.S. Patent No. 3,903,055 supra has remained the only feasible method of producing hw-multifunctional or long chain non-distillable cyanoacrylates.

Patent Publication DE 34 15 181 Al describes the preparation for the first time of α-cyanoacrylic acid which can be considered as the obvious precursor for alky Icy anoacrylates. The cyanoacrylic acid is prepared from a cyanoacrylic acid alkyl ester, in which the alkyl group contains from 2-18 carbon atoms, or the Diels-Alder adduct thereof by pyrolysis. The pyrolysis is preferably carried out on silicate-type surfaces such as quartz surfaces. The cyanoacrylic acid so prepared is indicated to be useful for stabilising or regulating the curing time of adhesives based on monomeric cyanoacrylic acid esters. It is also indicated that the cyanoacrylic acid so prepared can be used to prepare the diol esters of the acid. However, there is no indication in the specification as to how this can be accomplished.

Patent Publication JP 91 065340 describes a versatile route to pyruvic acid cyanohydrin and its esters as intermediates for the preparation of α-cyanoacrylate esters.

Patent Publication JP 91 075538 describes a-acetoxy-acyanopropionic acid esters which can be thermally converted to cyanoacrylate esters by elimination of a molecule of acetic acid.

Kandror I.I. et al. ((1990) Zh. Obsch. Khemii., Vol. 60, No. 9, p.2160-8) successfully converted α-cyanoacrylic acid (prepared according to Patent Publication DE 34 15 181 Al) to its acid chloride by the use of phosphorus pentachloride. Other chlorinating agents, such as thionyl chloride, were found not to be suitable. The product was obtained as a solution in o-xylene/toluene. Any attempts to isolate the pure product resulted in its decomposition. However, Kandror et al. successfully converted the acid chloride in solution to its thioester which spontaneously polymerised upon isolation. Kandror et al. have also successfully converted α-cyanoacrylic acid to its very unstable trialkylsilyl esters.

To date there have been no reports in the literature concerning the conversion of cyanoacrylic acid or its chloride to its alkyl ester monomers, whether short chain, long chain, bis or multifunctional cyanoacrylates, more particularly by a method which can be carried out on a commercial scale.

The preparation of a long chain cyanoacrylate (a thioester) by the strictly laboratory method of U.S. Patent No. 3,903,055 supra was synthesised by S.J. Harris ((1981) J. Polym. Sci. Polym. Chem. Ed.

Vol. 19, No. 10, p.2655-6). The n-dodecyl thiocyanoacrylate so prepared conferred improved moisture resistance when used as an additive in an ethyl cyanoacrylate adhesive.

Cyanoacrylate adhesive monomers, such as the most commonly used ethyl ester, can have their physical properties improved by the addition of linear organic polymers. Thus, non-reactive rubbers can be dissolved in such monomers to give adhesive compositions with much improved toughness/impact resistance when cured in the final adhesive bond. However, to date improvement in thermal/moisture resistance of rapid bonding cyanoacrylates has only been modest.

An improvement in adhesion, as well as toughness, would be expected if the non-reactive rubbers additionally contained chemically bound multi-cyanoacrylate functionality. Furthermore, it would be expected that any resulting increased cross-linked density could well provide significantly improved thermal moisture resistance to the final cyanoacrylate bond, relative to that of compositions containing only non-reactive rubbers.

J.P. Kennedy et al. ((1990) Am. Chem. Soc. Div. Polym. Chem. 31(2) p.255-6) prepared a cyanoacrylate-capped polyisobutylene by esterification of a hydroxy-terminated polyisobutylene. The method of U.S. Patent No. 3,903,055 supra was used to generate a multifunctional cyanoacrylate ester monomer which resulted in a copolymer being formed. Such copolymers have desirable properties for the reasons stated in the preceding paragraph.

Linear polymers such as poly(methyl methacrylate) are used as thickeners for cyanoacrylate monomers, so that the viscosity of the adhesive can be increased to a desirable level for a particular application. The use of cyanoacrylate-capped polyalkylmethacrylates as reactive thickeners would be expected to provide improved thermal/moisture resistance to the final joint and also improve the gapfilling ability of the adhesive.

Accordingly, for the above reasons, a method for generating cyanoacrylate esters on a practical and commercial scale is sought.

Accordingly, the invention provides a process for the preparation of esters of 2-cyanoacrylic acid, which process comprises reacting 2-cyanoacrylic acid or an acid halide thereof with an alcohol or a phenol in the presence of an inert organic solvent under polymerisation inhibiting conditions and, additionally, in the presence of an acid catalyst when 2-cyanoacrylic acid is a reactant, continually removing the water or hydrohalous acid produced and recovering the ester.

The process according to the invention can be used to prepare a wide range of cyanoacrylate esters, including substituted or unsubstituted long chain alkyl cyanoacrylates and multifunctional cyanoacrylates, including bis cyanoacrylates.

The process according to the invention can be carried out in a simple, rapid and facile, effectively one step process with the attendant advantages. Thus, the process according to the invention is a 'one pot' process in contrast with the prior art methods described above with their inherent limitations.

The term alcohol as used herein includes diols and polyols.

The preferred acid halide is the acid chloride.

The following reaction scheme depicts the reactions involving a) the acid and b) the acid chloride.

CN O CN O I II I II a) CH=C — C — OH + ROH-► CH = C — C — OR + H2O CN O CN O I II I II b) CH=C —C—Cl + ROH -► CH=C — C — OR + HC1 When 2-cyanoacrylic acid is used as a reactant, the acid catalyst is a non-volatile acid stabiliser.

Preferably, the acid catalyst is an anionic non-volatile acid stabiliser such as, for example, an aliphatic sulphonic acid, an aromatic sulphonic acid or a sultone. An essential characteristic of the acid catalyst is that it does not react with the alcohol or phenol. Especially suitable acid catalysts are methane sulphonic acid and p-toluene sulphonic acid.

Preferably, the process is carried out under anionic polymerisation inhibiting conditions. Such anionic polymerisation inhibiting conditions can involve the use of an excess of 2-cyanoacrylic acid, where cyanoacrylic acid is a reactant.

Alternatively, the anionic polymerisation inhibiting conditions can involve the use of a weak acid.

An especially suitable weak acid is sulphur dioxide, more especially gaseous sulphur dioxide which is bubbled into the reaction mixture, as further demonstrated below.

Further, preferably, when sulphur dioxide is used as an anionic polymerisation inhibitor, gaseous sulphur dioxide is bubbled into the reaction mixture as a continuous stream of sulphur dioxide.

Other anionic polymerisation inhibitors include aliphatic sulphonic acids, aromatic sulphonic acids, sultones, carbon dioxide and boron trifluoride.

Further, preferably, the process is carried out in the presence of a free radical polymerisation inhibitor.

A suitable free radical polymerisation inhibitor is benzoquinone, hydroquinone, methylhydroquinone or naphthoquinone.

The inert organic solvent can be any inert solvent which does not cause anionic polymerisation of cyanoacrylic acid or its esters. Suitable inert solvents include benzene, hexane, toluene and xylene.

The process according to the invention can be carried out at a temperature in the range 20-200°C, more especially 80-100°C.

When 2-cyanoacrylic acid is a starting compound, the esterification reaction is carried out under the conditions hereinabove specified with continual removal of water by azeotropic distillation.

Preferably, the total volume of the reaction solvent is kept constant.

Also preferably there is a gradual addition of alcohol or phenol into the reaction mixture.

When a cyanoacryolyl halide is a starting compound, an acid catalyst is not required as indicated above. In one embodiment the method of Kandror, I.I. (1990) supra can be used so that the cyanoacryolyl halide is reacted with the alcohol or phenol in sulphur dioxide saturated solvent under a dry inert gas such as argon. Other suitable inert gases include xenon, helium and nitrogen. The alcohol or phenol is added to the acid halide solution in sulphur dioxide - saturated solvent and the hydrohalous acid is removed as solvent is distilled off under a stream of sulphur dioxide and argon.

As an alternative to sulphur dioxide in the above embodiment, there can be used boron trifluoride.

In each case, the removal of water or hydrohalous acid, as appropriate, forces the reaction to go to completion, more particularly under boiling solvent conditions and stirring.

The process according to the invention can be used to prepare previously unobtainable, non-distillable cyanoacrylate monomers for a wide variety of uses. Cyanoacrylates prepared in accordance with the invention can be grafted onto polymer backbones to improve properties of said polymers such as thermal resistance. For example, phenyl cyanoacrylate prepared in accordance with the invention would inherently be expected to give more thermally resistant bonds on account of its aromaticity and would also be expected to be a low viscosity monomer similar to the methyl - and ethyl esters. As indicated above, to date improvement in thermal resistance of rapid bonding cyanoacrylates has been only modest. For example, the monomers can be prepared with a high number of ether linkages or multifunctional hydroxyl groups for the preparation of biodegradable drug or other active agent-containing nanocapsules or nanoparticles, more especially nanocapsules. Furthermore, drugs and other active agents can be chemically bound to such cyanoacrylates so as to achieve controlled release/absorption of the active agents with time.

Other uses for the cyanoacrylate monomers prepared in accordance with the invention include use in the preparation of a wide range of adhesives, including rapidly biodegradable medical adhesives or adhesives for temporary bonding.

Further specific examples of the uses of the cyanoacrylate esters prepared in accordance with the invention are indicated below.

U.S. Patent No. 3,903,055, supra describes bis cyanoacrylates as thermally resistant cyanoacrylate additives which are prepared from their respective anthracene adducts by displacement with maleic anhydride. However, as indicated above the bis cyanoacrylates so prepared are difficult to purify by this method.

The process according to the invention is versatile and can be used to produce a wide variety of bis cyanoacrylates according to the following general reaction scheme, wherein R can have a multiplicity of values as hereinabove described: CH H0C; co2h CN CN \ c c \x)ROC/ In the same way tri and tetrafunctional cyanoacrylates can be prepared in accordance with the invention, for example from pentaerythritol ch20, o \H c > CN =ch2 The quantities of tetrafunctional additive needed to provide significant improvements in cross-link density for thermal resistance improvement would be less than for bis cyanoacrylates. Polyfunctional cyanoacrylates can be readily synthesised in accordance with the invention from polyvinylalcohol as follows: (CH—CH2)n I o I c=o \=ch2 CN (CH—CH2)n I OH + H CN \ = cZ / \ co2h It is also postulated that further improvement can be rendered by attachment of cyanoacrylate units to a thermally resistant backbone containing OH functionality in the following manner.

H CN \ Ζ c=c co2h Ο ο ο Ί I I r C c \ ζ \ ζ \,ζ \ R' Ν— (R)—Ν Rx Ν—|ζ Vζ II ο CN ο I c=o CH.

It should be stated that the nitrogen of polyimides is not basic enough to seriously destabilise cyanoacrylate monomer.

Alternatively, it is postulated that cyanoacrylate 5 multifunctionality can be affixed on thermally resistant cyclic phenol formaldehyde resins called calixarenes of the following formula: CN n = 4, 5, 6, 7, 8 Anhydride-containing cyanoacrylates may be useful compounds provided functionality is added after removal of acid in the process according to the invention.

The relatively low resistance of cyanoacrylate bonds is due in part to shrinkage as monomer is converted to polymer. It is postulated that shrinkage on cure by cyanoacrylates (to polymer on bonding two surfaces together) and resultant stress cracking on heating can be minimised by incorporation of cyanoacrylate functionality into Bailey's spiroorthocarbonate monomers which expand upon cure (polymerisation). Acrylic rubbers have been incorporated into cyanoacrylate compositions to improve thermal resistance and impact strength and thus make them tougher, because cyanoacrylates are brittle in bonds. Further improvement in these properties may result from grafting cyanoacrylate functionality onto the acrylic rubber or nitrile rubber.

Poly (cyanoacrylate) bonds possess low moisture resistance and increased cross-link density should improve this property at the same time as improving the thermal resistance, because of the improved integrity of the polymer. The well known water repellant nature of silicones may be utilised in accordance with the invention by provision of silicone backbone multifunctional cyanoacrylates as cyanoacrylate additives as indicated by the following structural formula: O R R R O II iii || C — OCH2 -- -Si - O- Si - O-Si -- - CH2OC h2c = cZ R' R' R' c=ch2 \ / CN CN Compatibility with regular ethyl/methyl cyanoacrylate monomer would be improved by increasing the phenyl content of the silicone backbone with additionally an expected improvement in thermal resistance and oxygen permeability. The latter property is of particular interest as regards the oxygen permeability of wound dressings. More rubbery and flexible bonds may result, which property is particularly important in bonding highly dissimilar surfaces.

Grafting cyanoacrylate functionality onto a silicone backbone also has application in instant dental adhesives which could be formed in this manner and which would be stable in an aqueous environment.

In fact, liquid silicon containing cyanoacrylate monomers would be expected to possess an improved capacity for bonding RTV (Room Temperature Vulcanizing) silicone surfaces together depicted as follows: O R II I C— OCH2—Si-R' h2c = c \ CN I R Long alkyl chain cyanoacrylates prepared in accordance with the invention as additives may also provide improved moisture resistance of existing cyanoacrylate adhesive compositions and improved bonding to polyethylene as indicated by the following structural formula: Another aspect of the present invention is the bonding of difficult plastics. While polyethylene can be bonded with cyanoacrylate by prior application of amine primer, PTFE (polytetrafluoroethylene) and cyanoacrylate can only be bonded together with the greatest of difficulty employing plasma etching or by the use of highly toxic metal carbonyl primers. Employment of fluorine-containing alkyl cyanoacrylates as depicted by the following structural formula prepared in accordance with the invention may overcome this problem: CN • F H2C = c , \ I xC_O-CH2-C II I F F I I „ C-C-F I I F F Similarly, adhesion to polyvinyl acetate could be improved by an additive prepared by grafting cyanoacrylate units onto a polyvinyl acetate backbone on free hydroxy groups as follows: j_C_CH2-C-CH2-cj-n I o I c=o I ch3 I OH I o-c=o I CH, IcI o I c= I ch3 CH2—C—CH2—C-L I I J^n o o-c=o I I o c=o ch3 I C-CN II ch2 Bonding of perspex (polymethyl methacrylate) to itself may be improved by employment of a polymethacrylate containing grafted cyanoacrylate units as follows: CH3 I — C-CH2 — . I c=o I o I CH2CH2OH CH3 I C-CH2 — I n c = o o CH2CH2O —c = o I CH, 'CN Poly(methyl methacrylate) is, in fact, used as a thickener for cyanoacrylates and strength reduction of bonds utilising this inert nonreactive filler may be overcome by use of the above active compound. More importantly the gap filling ability of normal cyanoacrylate monomers is very poor, even thickened versions containing polymethyl methacrylate and thioxotropic cyanoacrylate compositions containing silanised silica. This gap filling property could be substantially improved by use of the additive having the above indicated structural formula.

Multifunctional methacrylates have already been shown to confer some (again modest) improvement in thermal resistance as additives with cyanoacrylate monomers, provided that a free radical curing agent is incorporated into the composition. Having the cyanoacrylate functionality attached directly to the multifunctional methacrylate in one molecule as depicted in the following formula is expected to provide some benefits over the two separate ingredients and is an example of the versatility of the process according to the invention: H,C=C CN Z O \ll coch2c o CH3 II I ch2oc-c=ch2· Such a molecule would be anionically and free-radically curing and would be expected to provide an instant cyanoacrylate with improved gap filling capability. Polymerisation of methacrylates is also accelerated in the absence of air.

Adhesion to Valox (a condensation of product of 1,4-butanediol and dimethyl terephthalate) used for electronic trimmers in the microelectronics industry, may be improved by additives prepared by grafting cyanoacrylate functionality onto polyvinyl formal resins, which is a technique which has been successfully employed for methacrylates, illustrated as follows: and which may also provide a way of bonding polyvinylformal films.

It is expected that adhesion to glass would be the result of incorporation of alkoxysilyl functionality into the cyanoacrylate monomer provided acid is removed following the esterification reaction, depicted as follows: CN C=C / \_ CN co2H CO2R I Si -(OR')3 Improved adhesion would result from Si-O-Si bond formation.

General metal adhesion could be improved by attachment of more polar groups onto the molecule, for example (Iron complexing moiety) The infinite variation of the value of R in cyanoacrylate esters prepared in accordance with the invention and having the following formula: H2C = CN / C Xco2r means that one can tailor the molecule for specific uses. For example, fine tuning could be made of the refractive index thereof when polymerised for bonding glass lenses together.

New low or pleasant odour cyanoacrylates may result from chemically binding cyanoacrylate to fragrance compounds such as vanillin as follows: SCN H2C = C Sometimes only temporary bonding is required and a more hydrophilic polyethylene glycol functional cyanoacrylate monomer of the following formula would be a likely candidate, debonding much faster than conventional cyanoacrylates in the presence of water: CN / h2c=c xcoch2ch2och2ch2och2ch3 Blooming or turning white on surfaces can be a problem with cyanoacrylates but with the infinite variety of monomers resulting from the process in accordance with the invention, this problem is more likely to be overcome.

Bonding of liquid crystal materials may be accomplished by the use of cholesterol-containing cyanoacrylates.

As indicated above drugs and other active agents may be chemically bound into the cyanoacrylate molecule. Following its polymerisation release of the active agent occurs by the hydrolytic breakdown in the body of the polycyanoacrylate. It is postulated that great control over such release could be achieved by chemical incorporation of the active agent, for example cortisone, into the polycyanoacrylate, for example, as follows: Variation of the substituent R in the cyanoacrylate esters prepared in accordance with the invention means that one can vary the hydrophilicity of the polymer and hence control the rate of breakdown by hydrolysis which is rapid when R is for example At present poly cyanoacrylate is used to microencapsulate drugs for gradual release into the body.

It is postulated that hydroxy-functional antibiotics/antifungal agents could be chemically bound into cyanoacrylates to provide additives for cyanoacrylate products for wounds, preventing infection while healing takes place. Antibiotic would not leach out as it would as a simple additive, but would remain only as long as the polycyanoacrylate bond lasts and the wound has healed naturally with accumulation of connective tissue.

Example 1 Synthesis of 2-cyanoacrylic acid Into a cracking apparatus consisting of a dosing funnel connected with quartz tube length (45 cm) provided with an electric heater, sulphur dioxide inlet tube and cold trap collector was charged 63 g (0.5 mole) ethyl 2-cyanoacrylate. The quartz tube was heated to 600°C. Cracking was carried out under 20 mm vacuum with continuous sparging with sulphur dioxide by dropwise addition of ethyl 2cyanoacrylate into the heated cracking quartz tube. After completion of cyanoacrylate addition the tube was cooled and the product collected in the cooled collector and recrystallised from toluene to give 15.6 g (32% yield) 2-cyanoacrylic acid m.p. 93-4^.^ NMR in (CD3)2 CO δ 11.7 (H)s CO2H, 7.1 (H)s=CHa, 6.9 (H)s=CHb ppm.

Example 2 Synthesis of chloroanhydride of 2-cyanoacrylic acid A mixture of 3.65 g 2-cyanoacrylic acid obtained according to Example 1 was added to 8.5 g phosphorus pentachloride, 0.01 g hydroquinone, 30 ml dry o-xylene and 30 ml dry toluene was stirred under a dry argon atmosphere for 10-15 minutes to give a colourless transparent solution. Phosphoryl chloride and half of the solvent was distilled off in vacuum. The residue was a solution of the pure chloroanhydride of 2-cyanoacrylic acid Ή NMR CeD6 55.9(H) dJ=l=CHa; 5.4(H) dJ=l = CHb.

Example 3 Preparation of 1.8-octanediol ///5(2-cyanoacrylate) from cyanoacrvlic acid Into a 0.5 litre flask fitted with mechanical stirrer, thermometer, sulphur dioxide inlet adaptor, dosing funnel protected with a drying tube (Drierite; Drierite is a Trade Mark) and a Liebig Condenser provided with a vacuum distilling adaptor and receiver flask was charged 250 ml sulphur dioxide inhibited anhydrous benzene containing 0.05 g hydroquinone, 0.1 g p-toluene-sulphonic acid and 3.88 g (0.04 mole) 2-cyanoacrylic acid (DE 34 15 181 Al supra). The dosing funnel was charged with sulphur dioxide inhibited anhydrous benzene. The solution was heated to reflux and 2.92 g (0.02 mole) 1,8octanediol was added gradually with stirring. The mixture was then added with stirring and constant distillation and removal of benzenewater azeotrope. While the azeotropic solvent distilled off additional anhydrous benzene was stirred at benzene reflux temperature for 0.5 hours after all the water had been removed. Then excess of solvent was distilled off to leave 50ml solution which was cooled and filtered and the solid recrystallised from sulphur dioxide inhibited anhydrous toluene to give 2.55 g (42%) 1,8-octanediol bis (2-cyanoacrylate) m.p. όϊ-δθσ^Η NMR C6D6 δ 7.05 (2H)s=CH2, 6.7 (2H)s=CH2, 4.3 4Ht OCH2, 1.2-2.0 12 Hm (CH2)6 ppm.

Example 4 Preparation of L2-ethyleneglvcol Z?is,(2-cyanoacrvlate) In a similar manner to that followed in Example 3 into a flask with stirrer, a sulphur dioxide inlet system, a dry dosing funnel and a Liebig Condenser with a receiver flask for collection of azeotrope was added 9.8 g (0.1 mole) of 2-cyanoacrylic acid and 0.2 g p-toluenesulphonic acid, 0.1 g methylhydroquinone and 250 ml dry analar benzene. The mixture was heated to reflux with stirring and continuous sparging with sulphur dioxide and gradually 0.372 g ethyleneglycol (0.06 mole) in 200 ml benzene was added at the same rate at which an azeotropic mixture of benzene and water was distilled off.

After the addition has been completed the mixture is refluxed until the azeotrope no longer comes off, while adding fresh dry benzene via the dosing funnel. After the azeotrope ceases to come over the mixture was boiled for a further 30 minutes while benzene distilled off until 100 ml remained in the reaction flask. Then the mixture was cooled and the product was filtered off and then recrystallised from anhydrous toluene to give 5.06 g (46% yield) 1,2-ethyleneglycol bis(2cyanoacrylate) m.p. 104-5°C Ή NMR in C6D6 ppm 07.1 (2H)s=CHa, δ6.7 (2H)s=CHb, 4.6 (4H)s OCH2 ppm.

Example 5 Preparation of 1.2-ethyleneglycol fris(2-cyanoacrylate) from cyanoacrvlovl chloride Into a 0.5 litre flask fitted with a mechanical stirrer, thermometer, sulphur dioxide stream inlet adaptor, argon inlet adaptor, dry dosing funnel (protected with a Drierite drying tube and Liebig Condenser provided with a vacuum distilling adaptor and receiver flask connected with a vacuum pump was charged 30 ml of a solution containing 4.64 g (0.04 mole) cyanoacryloyl chloride in 0-xylene and 220 ml sulphur dioxide saturated anhydrous toluene and 0.05 g methyl hydroquinone. The dosing funnel was charged with 200 ml sulphur dioxide inhibited anhydrous toluene. The reaction mixture was stirred at 20°C with a fast stream of sulphur dioxide and dry argon. Then 1.24 g (0.02 mole) of ethyleneglycol was added with stirring. The mixture was stirred under vacuum with the stream of sulphur dioxide and argon while toluene was distilled off with the hydrochloric acid. Additional toluene was added dropwise from the dosing funnel. After addition of the toluene excess solvent was distilled off under vacuum. The residue was recrystallised from sulphur dioxide inhibited anhydrous toluene to give 1.07 g (26%) 1,2-ethyleneglycol bis(2cyanoacrylate) m.p. 104-5^.^ NMR in C6D6 δ 7.1 2Hs=CH2, 6.7 2Hs=CH2, 4.6 4Hs OCH2 ppm.

Example 6 Synthesis of the n-hexadecvl ester of 2-cyanoacrvlic acid Into a 0.5 litre flask fitted with mechanical sitrrer, thermometer, argon inlet adaptor with a device for admitting a stream of gas under the surface of the reaction mixture, a dosing funnel protected with a Drierite drying tube, a Liebig Condenser provided with a vacuum distillation adaptor and a receiver flask connected to a vacuum flask was charged 0.98 g (0.01 mole) 2-cyanoacrylic acid, 50 mg methylhydroquinone, 200 ml dry benzene and 100 ml dry toluene. A solution of 2.08 g (0.01 mole) phosphorus pentachloride in 50 ml of dry toluene was charged into the dosing funnel. While sparging with dry argon and stirring under reflux the phosphorus pentachloride solution was added dropwise. Following completion of the addition the reaction mixture was boiled for 15 minutes following which the reflux condenser was substituted by a Liebig Condeser with a receiver and a calcium chloride drying tube and 200 ml of solvent were distilled off. At this point 2.42 g (0.01 mole) n-hexadecyl alcohol in 50 ml dry benzene was added from the dosing funnel while refluxing and stirring and sparging with dry argon. Following addition of the alcohol the mixture was boiled for one hour and then the solvent was distilled off to give 50 ml remaining which was cooled to 5°C and left overnight (17 hours), following which crystals of 2-cyanoacrylic acid had fallen out which were filtered off. The volatiles were removed by filtration under vacuum and the remaining solid recrystallised from hexane to give 1.57 g n-hexadecyl 2-cyanoacrylate (49% yield) solid; m.p. 513°C [Elemental Analysis Calculated for C20H35NO2 C = 74.8, H = .9, N = 4.4, Found C = 73.5, H = 11.1, N = 4.1], n-Hexadecyl 2cyanoacrylate has not heretofore been prepared.

XH NMR 56.24 (H)s=CHa, 5.38 (H)s=CHb, 3.89 (2H)t CH2 J=5.8Hz, 1.32(28H)m CH2, 0.91(3H)t CH3 13c NMR C 513.62 CH3, 22.29 CH3CH2, 31.56 CH3CH2CH2, 29.O(CH2)io, 25.27 CH3 (CH2)i2 CH2, 27.95 (CH3(CH2)i3CH2), 65.98 CH3 (CH2)i4 CH2O, 113.85 C, 115.99 CN, 159.78 C=O.

The invention is not limited to the embodiments described above which may be modified and/or varied without departing from the scope of the invention.

Claims (18)

Claims:

1. A process for the preparation of esters of 2-cyanoacrylic acid, which process comprises reacting 2-cyanoacrylic acid or an acid halide thereof with an alcohol or a phenol in the presence of an inert organic solvent under polymerisation inhibiting conditions and, additionally, in the presence of an acid catalyst when 2-cyanoacrylic acid is a reactant, continually removing the water or hydrohalous acid produced and recovering the ester.

2. A process according to Claim 1, wherein 2-cyanoacrylic acid is used and the acid catalyst is a non-volatile acid stabiliser.

3. A process according to Claim 2, wherein the acid catalyst is methane sulphonic acid or p-toluene sulphonic acid.

4. A process according to any preceding claim, which is carried out under anionic polymerisation inhibiting conditions.

5. A process according to Claim 4, wherein the anionic polymerisation inhibiting conditions involve the use of an excess of 2cyanoacrylic acid.

6. A process according to any one of Claims 1-4, wherein the anionic polymerisation inhibiting conditions involve the use of a weak acid.

7. A process according to Claim 6, wherein the weak acid is sulphur dioxide.

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

9. A process according to Claim 8, wherein the free radical polymerisation inhibitor is selected from benzoquinone, hydroquinone, methylhydroquinone and naphthoquinone.

10. A process according to any preceding claim, wherein the inert organic solvent is benzene, hexane, toluene or xylene.

11. A process according to any preceding claim which is carried out at a temperature in the range 20°-200°C. 5

12. A process according to any preceding claim, wherein the alcohol is a diol or a polyol.

13. A process according to Claim 1, substantially as hereinbefore described with particular reference to the accompanying Examples. 10

14. The n-hexadecyl ester of 2-cyanoacrylic acid.

15. An adhesive composition containing an ester of 2cyanoacrylic acid prepared in accordance with the process as claimed in any one of Claims 1-13.

16. A polymer formed from an ester of 2-cyanoacrylic acid 15 prepared in accordance with the process as claimed in any one of Claims 1-13.

17. A cross-linked polymer formed from an ester of 2cyanoacrylic acid prepared in accordance with the process as claimed in any one of Claims 1-13.

18. 20 18. A co-polymer containing a polymer formed from an ester of 2-cyanoacrylic acid prepared in accordance with the process as claimed in any one of Claims 1-13.