Process for the Preparation of 2-Cyanoacryloyl Chloride and Use of the Compound so Prepared for the Preparation of Esters of 2-Cyanoacrylic Acid

 WORLD INTELLECTUAL_ PROPERTY ORGANIZATION International Bureau INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (51) IIlte1'H3ti0l131 Patent C13-9SifiC3ti0n 6 3 (11) International Publication Number: WO 95/32183 C07C 253/30, 255/23 _ , , (43) International Publlcatlon Date: 30 November 1995 (30.11.95) (21) International Application Number: PCT/IE95/00017 (81) Designated States: AM, AU, BG, BR, BY, CA, CN, CZ, DE, EE, FI, GB, GE, HU, JP, KG, KP, KR, KZ, LK, LR, LT, (22) International Filing Date: 8 February 1995 (08.02.95) LV, MD, MN, MX, NO, NZ, PL, RO, RU, SD, SI, SK, TJ, UA, US, UZ, VN, European patent (AT, BE, CH, DE, DK, ES, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OAPI (30) Priority Data: patent (BF, BJ, CF, CG, CI, CM, GA, GN, ML, MR, NE, S940423 24 May 1994 (24.05.94) IE SN, TD, TG), ARIPO patent (KE, MW, SD, SZ). (71) Applicant (for all designated States except US): SALDANE Published LIMITED [IHIE]; Molyneux House, Bride Street, Dublin 8 With international search report. (IE). (72) Inventors; and (75) InventorslApplicants (for US only): DYATLOV, Valery Alexandrovich [RU/RU]; Malyl Levshinskyl per., 12-6, Moscow, 110934 (RU). MALEEV, Viktor [RU/RU]; Str. B, Apt. 66, Serpuchovskaya, 70, Moscow, 113093 (RU). (74) Agent: ANNE RYAN & CO.; 60 Northumberland Road, Ballsbridge, Dublin 4 (IE). (54) Title: PROCESS FOR THE PREPARATION OF 2—CYANOACRYLOYL CHLORIDE AND USE OF THE COMPOUND SO PREPARED FOR THE PREPARATION OF ESTERS OF 2-CYANOACRYLIC ACID (57) Abstract A process for the preparation of 2-cyanoacryloyl chloride in pure form comprises reacting 2-cyanoacrylic acid with a chlorinating agent, said reaction being carried out under side-reaction and polymerisation inhibiting conditions. A preferred chlorinating agent is a volatile chlorinating agent which forms only volatile by-products during the course of the reaction. Suitable volatile chlorinating agents include oxalyl chloride, sulfur oxychloride, trifluoroacetyl chloride and phosgene. Various methods can be used to inhibit polymerisation initiating conditions such as the use of a catalyst which forms an intermediate complex with the chlorinating agent, thereby preventing the formation of a mixed anhydride. The 2-cyanoacryloyl chloride formed can be used to form esters useful in the manufacture of adhesives and which esters are free of contaminants which would otherwise affect the setting time of the adhesives. AT AU BB BE BF BG BJ BR BY CA CF CG CH CI CM CN CS CZ DE DK ES FI FR GA FOR THE PURPOSES OF INFORMATION ONLY Codes used to identify States party to the PCT on the front pages of pamphlets publishing intemational applications under the PCT. Austria Australia Barbados Belgium Burkina Faso Bulgaria Benin Brazil Belarus Canada Central African Republic Congo Switzerland Cote d’Ivoire Cameroon China Czechoslovakia Czech Republic Germany Denmark Spain Finland France Gabon United Kingdom Georgia Guinea Greece Hungary Ireland Italy Japan Kenya Kyrgystan Democratic People's Republic of Korea Republic of Korea Kazakhstan Liechtenstein Sri Lanka Luxembourg Latvia Monaco Republic of Moldova Madagascar Mali Mongolia Mauritania Malawi Niger Netherlands Norway New Zealand Poland Portugal Romania Russian Federation Sudan Sweden Slovenia Slovakia Senegal Chad Togo Tajikistan Trinidad and Tobago Uldaine United States of America Uzbekistan Viet Nam I WO 95/32183 10 15 20 25 PCT/IE95/00017 Description Process for the preparation of 2-cyanoacryloyl chloride and use of the compound so prepared for the preparation of esters of 2-cyanoacrylic acid Technical Field This invention relates to a process for the preparation of 2- cyanoacryloyl chloride and to the use thereof in the preparation of esters of 2-cyanoacrylic acid. 2-Cyanoacryloyl chloride which has the formula: CN / H2C=' C \ 0- Cl ll 0 can potentially be used to prepare a wide range of cyanoacrylate monomers. Background Art The ability of 2-cyanoacrylates to polymerise rapidly under the influence of moisture or nucleophilic substances has led to their exploitation as instantaneous adhesives. However, the inherent ability ' of 2-cyanoacrylates to undergo rapid anionic polymerisation gives rise to complications as regards the synthesis of free 2-cyanoacryloyl chloride. Accordingly, whereas esters of 2-cyanoacrylic acid are known and well characterised since the 1940s, 2-cyanoacryloyl chloride has not been isolated and characterised. 2-Cyanoacryloyl chloride has been observed in solution only. The first reported observation of 2-cyanoacryloyl chloride in solution by NMR was described in 1990 by Kandror, I.I. et al. However, all efforts to isolate 2-cyanoacryloyl chloride from solution were unsuccessful. WO 95/32183 10 15 20 25 30 PCT/IE95/000 17 Kandror, I.l. et al. ((1990) Zh. Obsch. Khemii., Vol. 60, No. 9, p. 2160-8) have described two methods for the preparation of 2- cyanoacryloyl chloride—containing solutions. The first method involved the reaction of 2-cyanoacrylic acid with phosphorus pentachloride at a temperature of 110°C using a toluene—xylene mixture as a solvent, followed by distillation off of phosphorus oxychloride and a portion of the solvent. The resulting solution contained a mixture of 2—cyanoacryloyl chloride, polyphosphoric acid and polymers formed from 2-cyanoacrylic acid in the form of a solution in xylene. Conversion of 2-cyanoacrylic acid to 2—cyanoacryloyl chloride together with polymer was reported by NMR to be 95-99%, the yield of 2-cyanoacryloyl chloride was not estimated. 13C and 31P NMR analysis of 2—cyanoacryloyl chloride prepared by this method shows that deleterious by—products which are formed include those resulting from chlorination of, and addition of hydrogen chloride to, the olefinic bond of cyanoacryloyl chloride, and from the addition of phosphorus oxychloride to its nitrile group to yield substances containing the -C(Cl)=N-P(O)Cl;;_ function. 2- Cyanoacryloyl chloride obtained by this method cannot be isolated from the mixture and polymerises spontaneously once the solvent is distilled off in vacuo. Vacuum distillation or precipitation of the product with an inert solvent also leads to instantaneous polymerisation. The second method involved the reaction of 2-cyanoacrylic acid with thionyl chloride in toluene or toluene—xylene solution at a temperature of 110°C followed by distillation off of hydrochloric acid, sulfur dioxide and a portion of the solvent to give a mixture of 2—cyanoacryloyl chloride, 2-cyanoacrylic acid and polymers formed from 2-cyanoacrylic acid in the form of a solution in xylene. No yield or conversion has been estimated. NMR analysis shows that the product of the reaction is a solution of a mixture of 2—cyanoacryloyl chloride and 2-cyanoacrylic acid in a ratio of 65:35, together with mixed anhydride by-products resulting from the side and polymerisation reactions. Attempts to complete the reaction and WO 95/32183 10 15 20 25 30 PCT/IE95/00017 convert residual 2-cyanoacrylic acid and mixed anhydrides into 2- cyanoacryloyl chloride resulted in polymerisation of the mixed anhydrides, 2-cyanoacryloyl chloride and 2-cyanoacrylic acid. The 2—cyanoacryloyl chloride could not be isolated in pure form from the reaction mixture using this method and the yield could not be 5 estimated. However, according to NMR data, the yield is less than 65% and it appears that a significant amount of polymeric and side reaction products were not taken into account. Thus, pure 2-cyanoacryloyl chloride was not obtained and chemically characterised in accordance with either of the two methods described above. In the case of each method, 2- cyanoacryloyl chloride can only be obtained in the form of a solution contaminated with non-volatile by—products. 2-Cyanoacryloyl chloride is used as a starting material for obtaining esters of 2-cyanoacrylic acid. Because of the contamination of the 2-cyanoacryloyl chloride referred to above this necessitates that any resulting ester be purified to remove the contaminants formed during 2-cyanoacryloyl chloride production. If such contaminants, which are generally of an acidic nature, are not removed, these can affect the setting times of adhesives formed from the esters. The highest level of strongly acidic contamination tolerable in cyanoacrylate adhesive compositions is generally less than 1 p.p.m. As regards the contaminants, the most undesirable contaminants are traces of residual phosphorus oxychloride, non- volatile strong acids such as phosphoric and polyphosphoric acids, and the deleterious chlorinated by-products mentioned supra. These by-products can slowly release hydrochloric acid via hydrolysis by atmospheric moisture during, for example, storage of a cyanoacrylate adhesive composition, leading to loss of adhesive properties by acid inhibition of the anionic polymerisation pathway. Complicated procedures are required to purify the esters from the non-volatile mixtures of contaminants, in particular in the case of non—distillable liquid esters which cannot be purified by either distillation or by recrystallisation. W0 95/32183 10 15 20 25 PCT/H