CA2153342A1

CA2153342A1 - Process for the preparation of esters of 2-cyanoacrylic acid and use of the esters so prepared as adhesives

Info

Publication number: CA2153342A1
Application number: CA002153342A
Authority: CA
Inventors: Valery Alexandrovich Dyatlov; Georgy Arkadievich Katz
Original assignee: EUROTAX Ltd
Current assignee: EUROTAX Ltd
Priority date: 1993-01-11
Filing date: 1994-01-10
Publication date: 1994-07-21
Also published as: EP0682651A1; KR960700221A; WO1994015907A1; PL310073A1; JPH08505383A; AU5714294A

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 polymerization inhibiting conditions and, additionally, in the presence of an acid catalyst when 2-cyanoacrylic acid is a reactant, continually removing the water or hydrohalic acid produced and recovering the ester. The esters thereby prepared and many of which are novel compounds 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

~ 94115907 P~T/IE94/00002 21533~2 Description Process for the preparation of esters o~ 2-cyanoacrylic acid and use of the esters so prepared as adhesives Technical Field S 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. Many of these esters are novel compounds.

~3ackground Art 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 Knoevenagel Condensation Method (H.
I_ee. (Ed.) (1981) Cyanoacrylic Resins - The Instant Adhesives, Pasadena Technology Press, Pasadena, U.S.A.). According to the Knoevenagel method a cyanoacetate ester 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 Knoevenagel method is limited to the preparation of alkyl cyanoacrylates which have an alkyl moiety with no more than ten -) 94/15907 ~CTIE94/00002 21~33~2 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 5 literature to have been prepared by the Knoevenagel method and has been used in the preparation of a medical adhesive (Kublin, K.S. and Miguel, F.M., (1970) J. Amer. Vet. Med. Ass. Vol. 156, No. 3, p.313-8 and Alco, J.J. and DeRenzis, F.A., (1971) J. Pharmacol. Ther. Dent.
Vol. 1, No. 3, p.l29-32).

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

Additionall~, multifunctional cyanoacrylates, such as bis 15 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 20 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 acidi~lcation. The carboxylic acid is then converted to its acid 25 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 bis, multifunctional or long chain non-distillable cyanoacrylates.

~ 94115907 PCTI~E94/00002 21~33~2 Patent Publication DE 34 15 181 Al describes the preparation for the first time of (x-cyanoacrylic acid which can be considered as the obvious precursor for alkylcyanoacrylates. 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 oc-cyanoacrylate esters.

Patent Publication JP 91 075538 describes oc-acetoxy-ol-cyanopropionic acid esters which can be thermally converted to cyanoacrylate esters by elimin~tion of a molecule of acetic acid.

Kandror I.I. et al. ((1990) Zh. Obsch. Khemii., Vol. 60, No. 9.
p.2160-8) successfully converted a-cyanoacrylic acid (prepared according to Patent Publication DE 34 15 181 A1) 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 oc-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 ) 94/15907 PCT/IE9410000' 21~33~2 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 5 synthesised by S.J. Harris ((1981) J. Polym. Sci. Polym. Chem. Ed.
Vol. 19, No. 10, p.2655-6). The n-dodecylthio cyanoacrylate so prepared conferred improved moisture resistance when used as an additive In an ethyl cyanoacrylate adhesive.

Cyanoacrylate adhesive monomers, such as the most commonly lO 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 15 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 20 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 25 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 can be used as a glue which resulted in a copolymer being formed. Such copolymers have desirable properties for the reasons stated in the preceding paragraph. However, 30 such multifunctional cyanoacrylate monomers cannot be used as improving additives because of their insolubility in cyanoacrylates.

) 94115907 PCT/IE94100002 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 poly(alkyl methacrylates) S as reactive thickeners would be expected to provide improved theImaVmoisture resistance to the final joint and also improve the gap-filling ability of the adhesive.

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

10 Disclosure of Invention 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 15 conditions and, additionally, in the presence of an acid catalyst when 2-cyanoacrylic acid is a reactant, continually removing the water or hydrohalic 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 20 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' 25 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.

~) 94/15907 PCT/IE94/00002 6 21~33~2 The following reaction scheme depicts the reactions involving a) the acid and b) the acid chloride.
CN O CN O
l 11 1 11 a) CH C--C--OH + ROH 1~ CH - C--C--OR + H20 CN O CN O
l 11 1 11 b) CH-- C--C--Cl + ROH ~ CH C--C--OR +HCl 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. ~n 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 - 20 especially gaseous sulphur dioxide which is bubbled into the reaction rnixture, 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.

~ 94115907 PCT/IE94/00002 ` _ 21533~2 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 5 a free radical polymerisation inhibitor.

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

The inert or~anic solvent can be any inert solvent which does not cause anionic polymerisation of cyanoacrylic acid or its esters. Suitable 10 inert solvents include benzene, hexane, toluene, xylene and chlorinated hydrocarbons.

In the case of acid - catalysed esterification nitroalkanes can be used.

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

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 20 constant.

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

When secondary alcohols or phenols are being esterified in accordance with the invention, irrespective of whether 2-cyanoacrylic 25 acid or an acid halide thereof is used, the reaction should preferably be carried out in the presence of sulphur dioxide to optimize conditions, because of the tendency of the cyanoacrylate monomers produced to polymerise under the reaction conditions.

.) 94/15907 PCT/IE94/00002 21533~2 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 cyalloacryolyl halide is reacted with the alcohol or phenol in sulphur 5 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 hydrohalic acid is removed as solvent is distilled off preferably 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 hydrohalic acid, as appropriate, forces the reaction to go to completion, more particularly under boiling solvent conditions and stirring.

The invention also provides a novel method for the preparation of 2-cyanoacryloyl chloride, which comprises reacting 2-cyanoacrylic acid with phosphorus trichloride.

Many of the esters which can be prepared by the process according to the invention are novel compounds. Thus, in a further aspect of the invention there is provided esters of 2-cyanoacrylic acid of the general formula I:
CN
H C / O (I) o R

wherein R is i) C l l or C13 or higher saturated, optionally mono-or polysubstituted, linear-, branched- or cyclo-alkyl;
ii) C7-C1() saturated, optionally mono- or polysubstituted, branched alkyl;

. ) 94/15907 PCT/IE94/00002 21 5~3i~

iii) C7-Clo, optionally mono- or polysubstituted, cycloalkyl;
iv) C12 saturated, optionally mono- or polysubstituted, branched- or cyclo-alkyl;
v) Cs or higher unsaturated, substituted or unsubstituted, linear-, branched- or cyclo-alkenyl or -alkynyl;
vi) C2-C12 substituted alkyl where the or each substituent is a functional group which is not a free hydroxyl group, a hydroxyl group esterified by 2-cyanoacrylic acid, or an ether group;
vii) C2-C12 substituted alkyl where the alkyl group is substituted by more than one ether group;
viii) C13 or higher substituted alkyl where the or each substituent is a functional group;
ix) C3 or higher substituted alkyl where the or each substituent is a hydroxyl group;
x) Cs or higher substituted alkyl where the or each substituent is a simple or compound ether group;
xi) a mono- or polysubstitutedphenyl group;
xii) a mono- or polysubstituted biphenyl, naphthyl, anthracyl, phenanthryl or other cyclic or polycyclic aromatic or heteroaromatic group; or xiii) a hydroxy-termin~ted or a hydroxy-substituted oligomer or polymer.

Substituents can include heteroelements.

It will be appreciated that the main chain of any ester herein described can contain a heteroelement or ether function.

Functional groups which are representative of those which would 30 normally be used to substitute an R group as hereinabove defined include, for example, halogen, carboxyl, nitrile~ acyl-amino, unsaturated and heteroelement-containing groups.

. ~ 94/15907 I'CT/E 94/00002 21~33~2 In a still further aspect of the invention there is provided the mono- or bis(2-cyanoacrylate) esters of di-, tri-, tetra-, penta-, hexa-and poly-ethylene glycols or derivatives thereof.

As indicated above, the process according to the invention can be 5 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, aryl cyanoacrylates prepared in accordance with the invention 10 would inherently be expected to give more thermally resistant bonds on account of their aromaticity and would also be expected to be low viscosity monomers 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 15 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 20 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, sllpra 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.

~ 94/15907 PCTIIE94/00002 11 ` 21~33q2 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 H / CN CN / H
H2C C ~ . C C~ ~C = C

O o In the same way tri and tetrafunctional cyanoacrylates can beprepared in accordance with the invention, for example from pentaerythritol C--CH2~ll \C=CH2 CN

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 (CH--CH2)n OH
O +
EI CN
C--O ~ \C=C

C CE~ 2 H / \ CO2H
CN

12 21533~2 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:

O O
H CN
C- C
H/ \ - R--N R'--R R' N--R--=\/CN
1I n It should be stated that the nitrogen of polyimides is not basic enough to seriously destabilise cyanoacrylate monomer.

Alternatively, it is postulated that cyanoacrylate multifunctionality can be affixed on thermally resistant cyclic phenol 10 formaldehyde resins called calixarenes of the following formula:

~C~2--n O
C=O
C =CH2 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 13 21S33~2 that shrinL~age 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 5 (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 l 0 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 15 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
Il l l l 11 C--OCH2 - - -Si - O- Si- O-Si - - - CH20C
H2C = C R' R' R' C =C~12 CN CN

Compatibility with regular ethyl/methyl cyanoacrylate monomer 20 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 25 property is particularly important in bonding highly dissimiiar 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.

) 94/1~907 PCT/IE94/00002 14 21533~

In fact, liquid silicon containing cyanoacrylate monomers would be expected to possess an improved capacity for bonding RTV (Room Temperature Vulc.ani7.ing) silicone surfaces together depicted as follows:

C--OCH2--Si-R' H2C = C R" ~ ~

l,ong 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:
H ~CN
C=C
H C=O
\~
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 15 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 ~ormula:
CN
H C _/ O CF2--(CF2)n--CF3 Il o O 94/15907 PCT/l:E94/00002 21~33~2 prepared in accordance with the invention may overcome this problem.

Similarly, adhesion to polyvinyl acetate could be improved by an additive prepared by grafting cyanoacrylate units onto a partially hydrolysed polyvinyl acetate backbone on free hydroxy groups as 5 follows:

--CH2--C--CH2--C~n ~ C--CH2--C--CH2_C~
o OH O--C=O o O O--C=O
C--O CH3 C=O C=O CH3 Bonding of perspex poly(methyl methacrylate) to itself may be improved by employment of a poly(methyl methacrylate) containing grafted cyanoacrylate units as follows:

.
fl~3 fH3 C--CII2 ' C--CE~2--n I n - f=o f o. o CH2CH20H CH2CH20--C = O
,~c ~

Poly(methyl methacrylate) is, in fact, used as a thickener for cyanoacrylates and strength reduction of bonds utilising this inert non-reactive filler may be overcome by use of the above active compound.
More importantly the gap filling ability of normal cyanoacrylate 15 monomers is very poor, even thickened versions containing poly(methyl 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.

~ 94/15907 PCT/IE94100002 16 21 !;33~2 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 5 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:
CN
H2C = C~ 11 O CH3 COCH2C _ CH20C--C=CH2 3.

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 product of 1,4-butanediol and 15 ~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:

] [ 1 ] [
o o ~ CH2/ C=O C=O
C =CH2 CH3 CN
and which may also provide a way of bonding polyvinylformal films.

-~. ~ 94/~5907 . I'CTIIE94/00002 21S3~12 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:
H CN H CN
/ ' \
C--C ~ C =C
H ~CO2H H CO2R
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.

The infinite variation of the value of R in cyanoacrylate esters 1~ prepared in accordance with the invention and having the following formula:
CN
H2C = C

means that one can tailor the molecule for specific uses. For example, fine tuning could be made of the refractive index thereof lS 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:

- ~ . . ~ . .

~ 94/15907 . PCT/IE94/00002 ~1533~2 H--C =O
~, o ~C=O

H2C = C

~CN

Variation of the substituent R in the cyanoacrylate es~ers prepared in accordance with the invention means that one can vary the hydrophilicity of the polymer and hence control the rate of breakdown 5 by hydrolysis which is rapid when R is for example r~r~

O O o Sometimes only temporary bonding is required and a more hydrophilic polyethylene glycol functional cyanoacrylate monomer of the following formula:
CN
/

H2C = C

would be a likely candidate, debonding much faster than conventional cyanoacrylates in the presence of water.

E~looming or turning white on surfaces can be a problem with cyanoacrylates but with the in~lnite variety of monomers resulting 15 from the process in accordance with the invention, this problem is more likely to be overcome.

~ 94/15907 rCTllE94100~02 19 21~3i2 Bonding of liquid crystal materials might be accon,~plished by the use of sterol-containing cyanoacrylates.

As indicated above drugs and other active agents n~ay be chemically bound into the cyanoacrylate molecule. Following its 5 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:

2 3' 0 OH 11 1' H~CCH20H o O

~ ~ R--O C~I2--o--(CH2)nO--C\

0~ CN
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 15 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.

Carboxy-esters of the following general formula:
CN

\11/ \ (CE I2)nCO2H
O

`
~ 94/15907 PCT/IE94/00002 215~312 prepared in accordance with the invention may be useful as additives to control the setting times of cyanoacrylate-based adhesive compositions.

Furthermore, monomeric esters of the following general formula:
CN
H2C_/ O
~ \(CH2)nC02R
O

would be expected to exhibit usefully low vapour pressures and, therefore, to be less irritating to the user than conventional low molecular weight cyanoacrylates.

Best Modes for Carrying Out the Invention The invention will be further illustrated by the following Examples.

Example l 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 600C.
Cracking was carried out under 20 mm vacuum with continuous sparging with sulphur dioxide by dropwise addition of ethyl 2-cyanoacrylate 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~b yield) 2-cyanoacrylic acid m.p. 93-4C.lH NMR in (CD3)2 CO o 11 .7 (H)s CO2H, 7.1 (H)s=CHa, 6.9 (H)s=CHb ppm.

O') 94/15907 PCT/IE94/0000 21 21~33~2 Example 2 Svnthesis of 2-cyanoacryloyl chloride A mixture of 3.65 g 2-cyanoacrylic acid obtained according to Example 1, 8.5 g phosphorus pentachloride and 0.01 g hydroquinone in 5 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 2-cyanoacryloyl chloride lH NMR C6D6 o5.9(H) dJ=l=CHa; 5.4(H) dJ=l = CHb.

Example 3 Synthesis of 2-cyanoacryloyl chloride 0.98 g of 2-cyanoacrylic acid was added to 250 ml of boiling anhydrous toluene under a dry argon atmosphere. About 20 ml of toluene was distilled off and the solution was cooled to 60C when 2.7 15 ml of phosphorus trichloride was added. The rnixture was stirred at 60C during 6 hours with constant sparging of argon. It was then cooled to 15C and any unreacted phosphorus trichloride was distilled off in vacuum together with 100 ml of toluene. The rem~ining solution was decanted from polyphosphoric acid to give a colourless solution of 20 2-cyanoacryloyl chloride in toluene. In this Example toluene can be replaced as solvent by carbon tetrachloride.

Example 4 Preparation of 1.8-octanediol bis(2-cyanoacrylate) from cyanoacrylic 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 ` ) 94/15907 . PCTIIE94/00002 21~33~2 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 A1 supra). The solution was heated to reflux and 2.92 g (0.02 mole) of 1,8-octanediol 5 in 250 ml sulphur dioxide inhibited benzene was added gradually from the dosing funnel with stirring and constant removal of benzene/water azeotrope by distillation. While the azeotropic solvent distilled off additional anhydrous benzene was added, and the mixture was stirred at benzene reflux temperature for 0.5 hours after all the water had been 10 removed. Then excess of solvent was distilled off to leave 50 ml 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. 67-8C. lH NMR C6D6 7-05 (2H, s, CHa=C-), 6.7 (2H, s, CHb=C-), 4.3 (4H, t, -OCH2-), and 1.2-2.0 lS (12H, m, -(CH2)6-) ppm.

Example 5 Preparation of 1.2-ethvleneglycol bis(2-cyanoacrylate) In a similar manner to that followed in Exarnple 3 into a flask with stirrer, a sulphur dioxide inlet system, a dry dosing funnel and a 20 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-toluene-sulphonic acid, 0.1 g methylhydroquinone and 250 ml dry benzene.
The mixture was heated to reflux with stirring and continuous sparging with sulphur dioxide and gradually 0.372 g ethyleneglycol ~0.06 mole) 25 in 200 ml benzene was added at the same rate at which an azeotropic mixture of benzene and water was dishlled off.

After the addition had been completed the mixture was refluxed until the azeotrope no longer appeared, while adding fresh dry benzene via the dosing funnel. After the azeotrope ceased to come over the 30 mixture was boiled for a further 30 minutes while benzene was 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 ~ 94/15907 PCT/IE94/00002 ~1~3312 anhydrous toluene to give 5.06 g (46% yield) 1,2-ethyleneglycol bis(2-cyanoacrylate) m.p. 104-5C. lH NMR in C6D6 ~7.1 (2H, s, CHa=C-), 6.7 (2H, s, CHb-C-), 4.6 (4H, s, -OCH2-) ppm.

Example 6 Preparation of 1.2-ethyleneglycol bis(2-cyanoacrylate) from cyanoacryloyl 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 o-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 containing 1.24 g (0.02 mole) of ethylene glycol. ~he reaction rnixture was stirred at 20C with a fast stream of sulphur dioxide and dry argon. Then the ethylene glycol solution 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(2-cyanoacrylate) m.p. 104-5C.lH
NMR in C6D6 ~ 7.1 (2H, s, CHa=c-)~ 6.7 (2H, s, CHb-c-)~ 4.6 (4H, s, -OCH2-) ppm.

Example 7 Synthesis of the n-hexadecyl ester of 2-cyanoacrylic acid Into a 0.5 litre flask fitted with mechanical stirrer, thermometer, argon inlet adaptor with a device for admitting a stream of gas under ~) 94/15907 . rCT/lE94/00002 21~33~2 the surface of the reaction rnixture, a dosing funnel protected with a Drierite drying tube, a Liebig condenser provided with a vacuum distilla~ion 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 S0 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 rnixture was boiled for 15 minutes following which the reflux condenser was substituted by a Liebig condenser 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 rnl dry benzene was added from the dosing funnel while refluxing and stirrin~
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 5C and left overnight (17 hours), following which crystals of 2-cyanoacrylic acid had fallen out which were filtered off. The volatiles were removed by distillation under vacuum and the rem~ining solid recrystallised from hexane to give 1.57 g n-hexadecyl 2-cyanoacrylate (49~o yield) solid; m.p. 51-3C [Elemental Analysis Calculated for C2oH3sNo2 C = 74.8, H =
lO.9, N = 4.4, Found C = 73.5, H - 11. l , N = 4.1].

lH NMR â6.24 (lH, s, CHa=C-)~ 5.38 (lH, s, CHb=C-), 3.89 (2H, t, J=5.8Hz, -CH2OCO-), 1.32 (28H, m, (CH2)l4-), 0.91 (3H, t, -CH3) ppm. 13C NMR C ~13.62 CH3, 22.29 CH3CH2, 31.56 CH3CH2CH2, 29.0(CH2)lo, 25.27 CH3 (cH2)l2 CH27 7.95 (CH3(CH2)l3CH2), 65.98 CH3 (CH2)14 CH20, 113.85 C, 115.99 CN, 159.78 C=O.

Example 8 Preparation of 4~4'-isopropylidenediphenol b~s(2-cvanoacrylate) A solution of 0.01 mole of 2-cyanoacryloyl chloride (prepared as described in Example 3) in 120 ml of dry toluene was placed in a 500 -~) 94/15907 I'CT/IE94/00002 25 21~33~

ml flask fitted with a mechanical stirrer, a thermometer, argon and sulphur dioxide inlet adaptors, a dosing funnel and a Liebig condenser.
The solution was sparged with sulphur dioxide while 1 g of 4,4'-isopropylidenediphenol dissolved in 50 ml of hot toluene was added S dropwise. The stirred mixture was heated at 50C for two hours during which time it was sparged with argon and with sulphur dioxide.
The volume was then reduced in vacuum to 50 ml and the resulting solution was cooled and filtered. Residual solvent was removed in vacuum and the remaining yellow oil was washed with hexane to give a solid which was recrystallised from anhydrous benzene containing sulphur dioxide to give 4.4'-isopropylidenediphenol bis(2-cyanoacrylate) 1.21 g, 80%, m.p. 54-56C. IH NMR ~C6D6) 1.47 (6H, s. CH3), 5.53 (2H, s, =cH2)~ 6.21 (2H, s, =cH2)~ 6.72 and 7.04 (8H, ABq, J = 8 Hz. aryl H) ppm. A satisfactory elemental analysis was 1 5 obtained.

Example 9 Bis(2'-cyanoacrylate) ester of 1.3-di(4'-hvdroxybutyl)-1,1 3.3-tetramethyl- 1 .3-disiloxane A 500 ml flask was fitted with a stirrer, a thermometer, argon and sulphur dioxide inlet adaptors, a dosing funnel protected with a drying tube and a Liebig condenser arranged for distillation, and was charged with 150 ml of anhydrous toluene and 0.05 g of hydroquinone.
The mixture was refluxed, stirred and sparged with argon, while 1 g of 2-cyanoacrylic acid was added. 20 rnl of water-toluene azeotrope was distilled off, and then 2.2 g of phosphorus pentachloride in 50 ml of dry toluene was added dropwise with constant distillation of toluene.
The rnixture was stirred and refluxed for 1 hour and then sparged with sulphur dioxide while 50 ml of toluene containing by-product phosphorus oxychloride was distilled off to leave a colourless solution of 2-cyanoacryloyl chloride in toluene. A solution of 1.4 g of 1,3-di(4'-hydroxybutyl)-1,1,3,3-tetramethyl-1,3-disiloxane in 55 ml of toluene was added dropwise with stirring. The resulting mixture was heated for 1 hour, cooled~ and solvent removed in vacuum to leave ~) 9411~907 PCT/IE94100002 26 21~33~

2.1 g of a colourless oil. This oil was washed using hot hexane to leave 2.06 g of the title compound. Elemental Analysis Calculated for C2oH32ossi2N2: C 55.05%, H 7.34%, N 6.39%, Si 12.84%; Found: C
55.75%, H 7.59%, N 5.98%, Si 12.12%, lH NMR in (CD3)2CO:
0.0997 (12H, s, Si-CH3), 0.611 (4H, t, J = 9.4 Hz, Si-CH2), 1.498 (4H, m, Si-CH2C~2-), 1.769 (4H, m, C~l2cH2o-)~ 4.29 (4H, t, J = 5.6 Hz, CH2O-), 6.80 (2H, s, H-C=C-) and 7.067 (2H, s, H-C=C-) ppm.

Example 10 2-Cyanoacrylic acid ester of 2-hydroxypropyl-l-methacrylate/1-hydroxypropyl-2-methacrylate CH3 CN l H3 CN
CH2=C C =CH2 + CH2=C C =CE~2 Il, l 11 11 1 11 (X) (Y) The hydroxypropylmethacrylate used in tnis preparation was an approximately 2: l mixture of 2-hydroxypropyl- l -methacrylate and I -hydroxypropyl-2-methacrylate. A 500 ml flask was fitted with a 15 stirrer, a thermometer, argon inlet adaptor, dosing funnel protected wi~h a drying tube, and Liebig condenser arranged for distillation. The flask was charged with 150 rnl of anhydrous toluene and 0.05 g of hydroquinone. The mixture was refluxed while l g of 2-cyanoacrylic acid was added with stirring and sparging with argon. About 20 ml of 20 toluene-water azeotrope was distilled off. The mixture was then cooled and 0.94 g of phosphorus trichloride was added with stirring and sparging with argon. The resulting mixture was stirred at 45-50C for I hour and 30 rnl of solvent was then distilled off in vacuum to leave a colourless soluhon of 2-cyanoacryloyl chloride in toluene. A solution 25 of 1.4 g of hydroxypropyl methacrylate isomers in 20 ml of toluene was added dropwise to the stirred cyanoacryloyl chloride solution. The mixture was then heated at 45-50C for 1 hour, cooled, and evaporated ~ 94/15907 PCT/IE~4/00002 27 21533~

in vacuum to give 1.95 g of a colourless oil. This oil was washed with hot hexane to leave 1.65 g of a mixture of 2-cyanoacrylate esters of the isomeric hydroxypropyl methacrylates. Elemental Analysis Calculated for CllH13O N: C 59.0%, H 5.8%, N 6.2%, Found: C 55.75%, H 7.59%, N 5.98%, lH NMR in (cD3)2co 1.23 (3H, 2d, CH3-X, Y)~
1.93 (3H, s, CH3-,X, Y), 3.67 (0.7H, d, J = 6.3Hz, CH2O-, Y), 4.07 (1.3H, m, CH20-, X), 4.22 (lH, m, CH-, X, Y), 5.63 (lH, m, J = 7Hz, CHa=C-CH3,X,Y),6.12(1H,m,J=7Hz,CHb=C-CH3,X,Y),6.86 (lH, s, CHa=C-CN, X, Y), and 7.09 (lH, s, CHb=C-CN) ppm.

Examplell 2'-Carboxyethyl 2-cyanoacrylate 9.8 g of 2-cyanoacrylic acid, 0.2 g of 4-toluenesulphonic acid and 0.1 g of hydroquinone were dissolved in 250 ml of anhydrous benzene in a 500 ml flask which had previously been washed with 10 %
15 sulphuric acid and dried using acetone, and which was fitted with a stirrer, a thermometer, sulphur dioxide and argon inlet adaptors, a dosing funnel and a Liebig condenser arranged for distillation. The solution was sparged with sulphu~ dioxide and brought to reflux when a suspension of 9.9 g of 3-hydroxypropionic acid in 200 ml of benzene 20 was added dropwise with continuous removal of benzene-water azeotrope by distillation. The mixture was heated with stirring and sparging with sulphur dioxide until the benzene-water azeotrope ceased to appear, and was then refluxed for a further 30 minutes. The volume was reduced to 100 ml by removal of solvent by distillation. The 25 residual colourless solution was cooled, filtered, and diluted with 500 ml of heptane to give 8.S g of a solid which was collected. The solid was recrystallised from 1: 1 benzene: heptane which had been saturated with sulphur dioxide to yield 6.51 g of 2'-carboxyethyl 2-cyanoacrylate.

) 94/15907 PCTI~E94/00002 21~3312 Example 12 bis(2-Cyanoacrylate) ester of poly(butadiene)-~ -diol The poly(butadiene)diol used in this preparation was a hydroxy termin~ted resin of MW 2800 containing 60% trans-1,4-, 20% c~s-1,4-and 20% 1,2-vinyl units.

A 500 ml flask was fitted with a mechanical stirrer, a thermometer, argon and sulphur dioxide inlet adaptors, a dosing funnel protected with a drying tube and a Liebig condenser arranged for distillation, and was charged with 150 ml of anhydrous benzene and O.OS g of hydroquinone. The mixture was brought to reflux, stirred and sparged with argon, and 1 g of 2-cyanoacrylic acid was added.
About 20 ml of benzene-water azeotrope was distilled off and then 2.2 g of phosphorus pentachloride dissolved in 50 ml of dry benzene was added dropwise with stirring and constant removal of benzene by distillation. The mixture was refluxed during 1 hour, sparged with sulphur dioxide, and 50 ml of benzene containing by-product phosphorus oxychloride was removed by distillation to give a colourless solution of 2-cyanoacryloyl chloride in benzene. A solution of 0.05 g of hydroquinone and 12.6 g of poly(butadiene)diol in lS0 ml of dry benzene was added dropwise to the 2-cyanoacryloyl chloride solution with stirring and constant removal of benzene by distillation.
After refluxing for a further 1 hour the mixture was cooled and solvent removed in vacuum to give 13.5 g of high-viscosity yellow transparent polymer. This polymer was soluble in benzene, toluene, chloroform, hexane and heptane, but practically insoluble in alcohol, diethyl ether or ethyl 2-cyanoacrylate. Its solubility characteristics were retained when it was stored in a freezer, but cross-linking with accompanying loss of solubility took place on heating. The freshly-prepared polymer had IH NMR (C6D6) 2.11 (m, CH2-), 3.85(d, J 3.4 Hz, CH2(CH)-O)~ 3.94 (d, J 6.0 Hz, CH2(cH)-o)~ 4.34 (d, J 6.0 Hz, CH2-O-CO), 4.48 (d, J 6.0 Hz, CH2-o-co)~ 5.00, 5.03, 5.05 (ms, CH=C-), 5.36 (s. CH~=C(CN)-), 5.40 (s, CH2=C(CN)-), 5.48 (m, CH2=), 6.21 (s, CH. =C(CN)-) and 6.23 (s, CH2=C(CN)-) ppm.

~ 94/15907 PCT/IE94/00002 29 21~33~2 Example 13 2-Cyanoacrylic acid ester of polyethylene glycol 4-tert-octylphenyl ether A 500 ml flask was fitted with mechanical stirrer, thermometer, argon and sulphur dioxide inlet adaptors, dosing fuIlnel protected with a drying tube, and Liebig condenser arranged for distillation. The flask was charged with 250 ml of anhydrous toluene, and 1 g of 2-cyanoacrylic acid was added to the boiling solvent with stirring and sparging with argon. 20 ml of toluene/water azeotrope was removed by distillation and 2.2 g of phosphorus pentachloride dissolved in 50 ml of dry benzene was then added dropwise with stirring and constant removal of benzene by distillation. The mixture was stirred under reflux for 1 hour and then sparged with sulphur dio~ide, while lO0 ml of toluene containing by-product phosphorus oxychloride was distilled of~ to leave a residual colourless solution of 2-cyanoacryloyl chloride in toluene. A solution of 7.4 g of Triton-X100 (Triton is a Trade Mark) and 0.5 g of hydroquinone in 50 ml of benzene was then added dropwise to the 2-cyanoacryloyl chloride solution with stirring and constant removal of benzene by distillation. The mixture was refluxed during l hour, cooled, and solvent was distilled off in vacuum to give 8.1 g of a colourless oil which was washed with hot hexane to give 7.8 g of the 2-cyanoacrylate ester of polyethylene glycol 4-tert-octylphenyl ether. Elemental ~nalysis Calculated for C3gH63NO2: C
67.35%, H 9.30%, N 2.07%, Found C 66.7%, H 9.6%, N 1.9%, lH
NMR in 1: 1 C6D6: (CD3)2CO 0.75 (9H, s, (CH3)3C-), 1.37 (6H, s~
(CH3)2C-), 1.77 (2H, s, CH2)~ 3.62 (m, CH2O-), 3.98 (t, J = 4 Hz, CH2O-), 4.13 (t, J = 5 Hz, CH2O-), 4.43 (m, 2H, CH2OCO-), 6.08 (s, lH, H-C=C-), 6.67 (s, lH, H-C=C-), 6.88 and 7.33 (2d, each 2H~ A2B2, J = 7.2 Hz, aryl) ppm.

-~) 94/15907 PCT/IE94/00002 21~33~2 Example 14 bis(2-Cvanoacrylate) ester of diethyleneglycol A 500 ml flask was fitted with a mechanical stirrer, a thermometer, argon and sulphur dioxide inlet adaptors, a dosing funnel protected with a drying tube and a Liebig condenser arranged for distillation. The flask was charged with 150 ml of anhydrous benzene and 0.05 g of hydroquinone, and then l.0 g of 2-cyanoacrylic acid was added to the refluxing mixture with stirring and sparging using argon.
About 20 ml of water-benzene azeotrope was removed by distillation, and 2.2 g of phosphorus pentachloride dissolved in 50 ml of dry benzene was then added dropwise with constant stirring and removal of benzene by distillation. The mixture was refluxed for 1 hour, sparged using sulphur dioxide, and then 50 ml of benzene containing by-product phosphorus oxychloride was removed by distillation to leave a colourless solution of 2-cyanoacryloyl chloride in benzene. A solution of 0.4 g of diethylene glycol in 55 ml of benzene was dried by distilling off lO ml of a benzene-water azeotrope, and the dried solution was then added dropwise to the 2-cyanoacryloyl chloride solution with stirring.
The mixture was heated for l hour. cooled, and solvent removed by distillation in vacuum to leave 1.5 g of a colourless oil. This was washed using hot hexane to give 1.15 g (75%) of the title compound.
Elemental Analysis Calculated for Cl~Hl2OsN2: C 54.54%, H 4.54%, N 10.60%; Found C 55.12%, H 4.68~o, N 9.89%, lH NMR (C6D6) 3.10 (4H, t, J 6 Hz, CH20CH2), 3.90 (4H, t, J 6 Hz, C~I2-O-CO), 5,48 (2H, d, J 1 Hz, CHa=C-), 6.31 (2H, d, J 1 Hz, CHb=C-) ppm.

Example 15 2-Cyanoacrylic acid ester of 2-hydroxyethyl-l-methacrylate A 500 ml flask was fitted with a mechanical stirrer, a 30 thermometer, argon and sulphur dioxide inlet adaptors, a dosing funnel protected with a drying tube, and a Liebig condenser arranged for distillation. The flask was charged witll lS0 ml of anhydrous benzene ~) 94tl5907 PCT/~E94/00002 31 21S33~2 and 0.05 g of hydroquinone, and then 1.0 ~ of 2-cyanoacrylic acid was added to the refluxing mixture with stirrin~ and sparging using argon.
About 20 ml of beuzene-water azeotrope was removed by distillation and 2.2 g of phosphorus pentachloride dissolved in 50 ml of dry 5 toluene was added dropwise with stirring and constant removal of benzene by distillation. The mixture was refluxed for 1 hour, sparged using sulphur dioxide, and 50 ml of a benzene-toluene mixture containing by-product phosphorus oxychloride was distilled off to leave a colourless solution of 2-cyanoacryloyl chloride. A solution of 1.2 g 10 of 2-hydroxyethyl-1-methacrylate in 50 ml of benzene was added dropwise to the cyanoacryloyl chloride solution. The mixture was refluxed for 1 hour, cooled, and solvent was distilled off in vacuum to give 2.0 g of a colourless oil. This was washed using hot hexane to leave 1.65 g (75%) of the title compound. Elemental Analysis Calculated for CloH1104N: C57.41%, H5.21%, N6.69%; Found C 57.11%, H 5.48%, N 6.14%, lH NMR (C6D6) 1.80 (3H, s, CH3), 4.08 (4H, s, -OCH2CH20-), 5.32 (lH, s CHa=C(CH3)), 5.88 (lH, s CHa=C(CN)), 6.07 (lH, s, CHb=C(CH3)), 6.45 (lH, s, CHb=C(CN)) ppm.

Claims

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 hydrohalic 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 2-cyanoacrylic 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, xylene or a chlorinated hydrocarbon.

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

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

13. Esters of 2-cyanoacrylic acid of the general formula I:

(I) wherein R is i) C11 or C13 or higher saturated, optionally mono-or polysubstituted, linear-, branched- or cyclo-alkyl;
ii) C7-C10 saturated, optionally mono- or polysubstituted, branched alkyl;
iii) C7-C10 optionally mono- or polysubstituted, cycloalkyl;
iv) C12 saturated, optionally mono- or polysubstituted, branched- or cyclo-alkyl;
v) C5 or higher unsaturated, substituted or unsubstituted, linear-, branched- or cyclo-alkenyl or -alkynyl;
vi) C2-C12 substituted alkyl where the or each substituent is a functional group which is not a free hydroxyl group, a hydroxyl group esterified by 2-cyanoacrylic acid, an ether group or a chloroethyl group and when R is a group of the formula -R1CO2R2, R1 is not -CH2 or -CH-CH3 when R2 is alkyl, alkenyl or alkynyl of up to four carbon atoms;
vii) C2-C12 substituted alkyl where the alkyl group is substituted by more than two ether groups;

viii) C13 or higher substituted alkyl where the or each substituent is a functional group;
ix) C3 or higher substituted alkyl where the or each substituent is a hydroxyl group;
x) C5 or higher substituted alkyl where the or each substituent is a simple or compound ether group;
xi) a mono- or polysubstituted phenyl group;
xii) a mono- or polysubstituted biphenyl, naphthyl, anthracyl, phenanthryl or other cyclic or polycyclic aromatic or heteroaromatic group; or xiii) a hydroxy-terminated or a hydroxy-substituted oligomer or polymer.

14. The mono- or bis(2-cyanoacrylate) esters of di-, tri-, tetra-, penta-, hexa- and poly-ethylene glycols or derivatives thereof.

15. An adhesive composition containing an ester of 2-cyanoacrylic acid prepared in accordance with the process as claimed in any one of Claims 1-12.

16. A polymer formed from an ester of 2-cyanoacrylic acid prepared in accordance with the process as claimed in any one of Claims 1-12.

17. A cross-linked polymer formed from an ester of 2-cyanoacrylic acid prepared in accordance with the process as claimed in any one of Claims 1-12.

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 1-12.