Non Hydroquinone Cyanaoacrylate Cracking Process

US 20080l08844Al (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0108844 A1 Baggaley (43) Pub. Date: May 8, 2008 (54) NON HYDROQUINONE CYANOACRYLATE (30) Foreign Application Priority Data CRACKING PROCESS NOV. 2, 2006 (GB) .............................. .. GB062l98.l (76) Inventor: John Baggaley, Oakham (GB) Publication Classification (51) Int. Cl. C07C 253/30 (2006.01) Correspondence Address: C07C 255/40 (2006.01) ALTIMATIA, L.L.C. (52) US. Cl. ....................................... .. 558/357; 558/441 16 ELM RIDGE ROAD (57) ABSTRACT PENNINGTON, NJ 08534 A process for producing a monomer comprising thermally cracking a pre-polymer in the presence of a stabiliser to form (21) App1.No.; 11/854,639 a monomer as a distillate , the stabiliser preventing the re- polymerisation of the monomer during cracking while not being carried over in the distillate in normally detectable (22) Filed: Sep. 13, 2007 amounts. US 2008/0108844 A1 NON HYDROQUINONE CYANOACRYLATE CRACKING PROCESS CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of GB Patent application number GBO62198.1-Filed 2nd November 2006. [0002] Process for Producing a Monomer [0003] The present invention relates to a process for producing a monomer particularly a monomer of a cyanoacrylate. [0004] The process is especially suitable for producing a monomer for application as an adhesive particularly for medical applications e.g. sealing wounds and joining broken bones without the need for extemal mechanical appliances such as sutures. [0005] The process is also particularly suitable for pro- ducing an adhesive for cosmetic applications e.g. for the decoration of finger and toenails. [0006] Generally speaking these adhesives are made using an alkyl cyanoacrylate pre-polymer which itself is prepared by reacting formaldehyde with a cyanoacetate which may be methyl, ethyl or other homologue in the presence of a base such as piperidine, water then being removed to provide a pre-polymer of a cyanoacrylate. [0007] In order to produce the monomer the cyanoacrylate pre-polymer is cracked by a thermolytic distillation process and the monomer is distilled over to a receiving vessel. [0008] In order for the crack to be effective, acids in the form of known anionic stabilisers to stop anionic re-poly- merisation during the formation of the monomer are added to the pre-polymer. In addition known radical stabilisers (also known as anti-oxidants) are also added to the pre- polymer to stop radical re-polymerisation of the monomer during the cracking process. [0009] The crude cyanoacrylate monomer is then re-dis- tilled and stabilised with anionic acid and radical stabilisers to prevent the monomer re-polymerising i.e. solidifying during storage and before use. [0010] One problem with the current radical stabilisers used in the thermolytic process is that they tend to be carried over in the distillate. This is undesirable as their excessive loss from the polymer solution during the cracking process leaves it depleted in the particular stabiliser and therefore unstable. The polymer solution forms degradation products with associated reduced yields of the monomer. This stabi- lizer carry over phenomenon also restricts the temperature and vacuum at which the cracking and distillation can be undertaken and reduces process efficiency. [0011] Another problem is that the currently preferred radical stabilizers for the cracking process are usually poten- tially harmful compounds such as hydroquinones or closely related alkylphenols with hydoquinone impurities and it is undesirable that they are carried over and present in signifi- cant amounts in the distilled monomer and thereafter in derived adhesive formulations, especially when these are to be used on the human body for say medical and/ or cosmetic applications. These adhesive formulations in turn require stabilizers, including radical stabilizers, to provide adequate shelf-life but at the same time not unduly compromising adhesive curing performance which is affected by radical stabilzers. The currently preferred radical stabilizers for the cracking process are not necessarily the optimum stabilizers May 8, 2008 for the derived adhesive products and their presence com- promises adhesive curing performance. [0012] It is therefore an object of the present invention to provide a process whereby there is no carry over of the stabilisers in the thermolytic process or any such carry over of such stabilisers in monomers is held below the level where any toxins are present in potentially harmful amounts and, in addition, allow adhesive products to be subsequently formulated with selected suitable stabilizers to provide opti- mum shelf life stability and curing performance. [0013] According therefore to the present invention, a process for producing a monomer comprises thermally cracking a pre-polymer in the presence of a stabiliser to form a monomer as a distillate, the stabiliser preventing the re-polymeri sation of the monomer during cracking while not being carried over in the distillate in normally detectable amounts. [0014] The thermal cracking process may take place under a vacuum. [0015] Preferably the stabiliser has a vapour pressure which is such that at the temperature at which the pre- polymer cracks and the monomer distillate is formed, the stabiliser is not carried over to the distillate during the cracking process in normally detectable amounts. [0016] Suitably the stabiliser has a vapour pressure which is lower than the boiling point of the prepolymer so that the stabiliser is not carried over to the distillate during the cracking process in normally detectable amounts. [0017] Conveniently the stabiliser has a molecular weight which is sufiiciently high such that the stabiliser is substan- tially not carried over to the distillate during the cracking process in normally detectable amounts. [0018] The stabiliser which is present during thermal cracking may be a sterically hindered polyphenolic com- pound. [0019] In one embodiment the stabiliser is selected from 1,3 ,5 -trimethyl-2,4,6-tris(3 , 5-di-tert-butyl-4 -hydroxyben- zyl) benzene available as proprietary brands Anox 330 (Trade Mark) or Irganox 1330 (Trade Mark). [0020] In another embodiment the stabiliser is hexaphe- nol. [0021] In yet another embodiment the stabiliser is 1,1 Bis (2-methyl-4-tert-butylphenyl) butane available as the pro- prietary brand Lowinox 44B25 (Trade Mark). [0022] In a still further embodiment the stabiliser is 1,1, 3-Tris (2-methyl-4-hydroxy-5-t-butylphenyl) butane avail- able as a proprietary brand Lowinox CA 22 (Trade Mark). [0023] Preferably a stabiliser is added to the monomer so produced as the distillate to prevent the monomer reverting to the pre-polymer. [0024] Suitably the selected stabiliser is a radical stabiliser which is added in the exact required amount. [0025] Conveniently the radical stabiliser is selected from quinone, hydroquinone, p-tert-butyl catechol, p-methoxy phenol, 2,6-di-tert-butyl-p-cresol and 2,2-methylene-bis-(4- methyl-6-tert-butyl) phenol but this is by no means an exhaustive list and other unmentioned radical stabilisers may well be suitable and effective. [0026] The stabiliser to be added to the monomer may be an anionic stabiliser which again can be added in the exact desired quantity. [0027] In this case the anionic stabiliser is selected from methane sulphonic acid, p-toluene sulphonic acid, trifluo- romethane sulphonic acid, hydroxy propane, sulphonic acid, US 2008/0108844 A1 sulphur dioxide and hydrofluoric acid but here again this is by no means an exhaustive list and other unmentioned anionic stabilisers may well be suitable and effective. [0028] Suitably the pre-polymer is a cyanoacrylate com- pound which may be an alkyl, alkoxy, cycloaliphatic, unsat- urated alkyl or aromatic cyanoacrylate. [0029] Conveniently the cyanoacrylate is selected from a methyl, ethyl, n-propyl, iso propyl, n-butyl, iso-butyl, n-pen- tyl, 2-pentyl, 3-pentyl, n-hexyl, 2-hexyl, 3-hmay well be suitable hexyl, n-heptyl, 2-heptyl, 3-heptyl, 4-heptyl, n-oc- tyl, 2-octyl, 3-octyl, methoxy ethyl, ethoxy ethyl, propoxy propyl, cyclobutyl, cycloheptyl, cyclohexyl, cyclooctyl, cyclopentyl and allyl cyanoacrylate but as before this is by no means an exhaustive list and other unmentioned cyanoacrylates may well be suitable and effective. [0030] In one embodiment of the invention the cyanoacry- late pre-polymer is made from the reaction of a cyanoacetate and formaldehyde. [0031] Preferably piperidine is added to the mixture to act as a catalyst. [0032] Suitably the formaldehyde is paraformaldehyde. [0033] Heptane may be added to the mixture to act as an azeotrope solvent but the addition of heptane is not essential and the reaction to form the prepolymer can take place in a mixture which is solvent-free. [0034] An embodiment of the invention will now be particularly described with reference to the following example: [0035] In this embodiment the pre-polymer is manufac- tured immediately prior to its being cracked to form the monomer. It will be appreciated however that it would be possible to crack the pre-polymer from an already prepared pre-polymer bought off the shelf so to speak. [0036] The prepolymer to be manufactured in this example is ethyl cyanoacrylate. This is prepared from ethyl cyanoacetate and paraformaldehyde as the basic constitu- ents. [0037] The equipment described hereinafter in both the preparation of the pre-polymer and in the cracking process is conventional and well known in the art and so will not be described in detail. [0038] Firstly, in order to prepare the prepolymer, all the compounds to form it are added to a conventional three necked 500 ml borosilicate glass mixing vessel fitted with a stirrer. There is also provided a known type Dean and Stark condenser connected to an outlet end of the mixing vessel together with a monomer receiving vessel for receiving the monomer condensate. The receiving vessel is connected to an outlet end of the condenser, a thermometer being pro- vided to measure the temperature of the contents of the glass mixing vessel and a heating mantle to heat the contents of the glass vessel. [0039] To the glass mixing vessel are added 241 gm of ethyl cyanoacetate, 0.7 gm piperidine, 60 gm of paraform- aldehyde and 70 gm heptane which takes no part in any reaction but merely acts as a solvent. The cyanoacetate, piperidine and paraformaldehyde are reacted together under reflux conditions with any water forming in the vessel as a result of the reaction being removed by azeotropic distilla- tion via the Dean and Stark condenser as is conventional. [0040] Secondly, in order to prepare the monomer from the prepolymer just produced iin the mixing vessel, 6.9 gm of phosphorus pentoxide, 0.6 gm p-toluene sulphonic acid and 4.6 gm of Anox 330 are added to the prepolymer in the May 8, 2008 mixing vessel. The glass mixing vessel is then heated by the mantle so that the prepolymer is allowed thermally to depolymerise or crack at a temperature of between 140 and 180° C. under a vacuum of 7>X< * >X< *