Novel alpha-cyanoacrylate compound, method of preparing same and adhesive comprising same

EP 0 127 855 A1 Européisches Patentamt 0’ European Patent Office Office européen des brevets O 1 27» 855 A1 ® Publication number: ® EUROPEAN PATENT APPLICATION @ Application number: 841059827 @ Int. CL“: C 07 C 121/413 A 61 L 15/O6 ® Date offilingz 25.05.34 @ Priority: 3o.o5.s3 JP 95735133 @ Applicant: Kabushiki Kaisha Alpha Giken 1-3-4-, Kasuga lbaraki-shi Osaka-fu(JP) @ Date of publication of application: 12.12.84 Bulletin 34/5o @1nventor: l-lirakawa,Eisuke 11-7, Nagaycshi-Rokutan 2-chome Designated Contracting States: Hirano-ku Osaka-shi(JP) DEFRGB Representative: Tfirk, Dietmar, Dr. rer. nat. et al, Redies, Redies, Turk & Gille Patentanwilte Brucknerstrasse 20 D-4000 Dusseldorf 13(DE) @ Novel alpha-cyanoacrylate compound, method of preparing same and adhesive comprising same. oz-cyanoacrylate compounds expressed by the following general formula: FIG. 1 CN CH: wherein R‘ designates-CHz—or— CH—and R’ designates alkyl groups, alkenyl groups or alkynyl groups of C1 to C4. These compounds are preferably synthesized by the reaction of the compounds expressed by the following general formula: NC—CHz—C—OR‘—C—O—R’ O! p. 3 @- ~l O U! .0 on. N ..a 0 II N o 0 wherein R‘ and R‘ are same as the above described, with formaldehyde products and then the depolymerization ofthe resulting dehydrating condensation polymers. These com- pounds are effectively used as fast-setting adhesives. Croydon Printing Company Ltd. 10 15 2O 25 0127855 NOVEL a—CYANOACRYLATE COMPOUND, METHOD OF PREPARING SAME AND ADHESIVE COMPRISING SAME BACKGROUND OF THE INVENTION The present invention relates to the novel a- cyanoacrylate compounds, a method of preparing same and adhesives comprising same. a-cyanoacrylate compounds expressed by the following general formula have been well known as instant adhesives: H CN \ / [C = C‘\ H C - O - R H 0 Such adhesives are fast set time and put together the substrates made of various kinds of material with each other strongly. a—cyanoacry1ate compounds expressed by the above described general formula, in which R is alkoxyalkyl group, halogenated alkyl group, alkenyl group, alkynyl group or the like in addition to alkyl group, have been known. However, almost of them have such disadvantageous that they have an irritating odor whereby being disadvantageous in handling, the cir- cumference of the surfaces bonded being whitened, and the polymerization set products being fragile whereby having lower impact resistance and bending resistance. 10 15 20 25 0127855 It is an object of the present invention to pro- vide novel 0-cyanoacrylate compounds. It is another object of the present invention to provide a novel method of preparing said¢z- cyanoacrylate compounds. It is further an object of the present invention to provide novel adhesives comprising same a-cyano- acrylate compounds. SUMMARY OF THE INVENTION The inventor of the present invention synthesized various kinds of u-cyanoacrylate compound and investi- gated their properties and bonding performance to various kinds of substrate (including living bodies). As a result, it was found that the novel a-cyanoacry- late compounds expressed by the following general formula solved the above described disadvantages and had a superior bonding performance. cm H I ‘c=c—c-0-121-c—o—R2 / H I? II 0 oc H3 wherein R1 designates — CH2 - or - éfi - and R2 desig- nates alkyl groups, alkenyl groups or alkynyl groups 0 of C1 to C4. Said urcyanoacrylate compounds are preferably prepared by the reaction of the compounds expressed 10 15 20 25 0127855 by the following general formula with formaldehyde products and then the thermal depolymerization of the resulting dehydrating condensation polymers: 2 NC - CH2 — c — 0 — R1 — c — o — R H H O 0 1 and R2 are same as the above described. wherein R BRIEF DESCRIPTION OF THE DRAWINGS ____________________________________ 1 Fig. 1 shows a H—NMR spectrum of the compound 1 (ethoxycarbonylmethyl a—cyanoacrylate) of the com- pounds according to the present invention: Fig. 2 shows a mass spectrum of said compound 1; Fig. 3 shows an IR-spectrum of said compound 1; 1 Fig. 4 shows a H-NMR spectrum of the compound 2 (methoxycarbonylmethyl a—cyanoacrylate) of the com- pounds according to the present invention: Fig. 5 shows a mass spectrum of said compound 2; Fig. 6 shows an IR-spectrum of said compound 2; 1 Fig. 7 shows a H—NMR spectrum of the compound 4 (allyloxycarbonylmethyl a—cyanoacrylate) of the com- pounds according to the present invention; Fig. 8 shows a mass spectrum of said compound 4; Fig. 9 shows an IR-spectrum of said compound 4; Fig. 10 shows a 1H—NMR spectrum of the compound 6 (1-ethoxycarbonylethyl a-cyanoacrylate) of the com- pounds according to the present invention; 0127855 Fig. 11 shows a mass spectrum of said compound 6; and Fig. 12 shows an IR-spectrum of said compound 6. DESCRIPTION OF THE INVENTION 5 The novel u-cyanoacrylate compounds according to the present invention are expressed by the following general formula: CN H I 2 \C=C-C-0-R1"C"‘0"R H’ u H 0 1° 0 CH3 I wherein R1 designates - CH2 - or - CH - and R2 desi- gnates alkyl groups, alkenyl groups or alkynyl groups of C to C4. 1 Said compounds are diesters containing two ester 15 parts in one molecule. Concretely speaking, they include methoxycarbonylmethyl a-cyanoacrylate, ethoxycarbonylmethyl u-cyanoacrylate, butoxycarbonylmethyl u-cyanoacrylate, 20 allyloxycarbonylmethyl a-cyanoacrylate, propargyloxycarbonylmethyl u—cyanoacrylate, 1-methoxycarbonylethyl u—c¥anoacry1ate, 1-ethoxycarbonylethyl u-cyanoacrylate, .l—butoxycarbonylethy1 u—cyanoacrylate, 25 l-allyloxycarbonylethyl a—cyanoacrylate and the 10 15 20 25 0127855 like. Olefinic protons of a-cyanoacrylate were common- compounds expressed by the above described general formula, respectively. Protons of - CH2 - put between two ester parts were observed in the form of single signal at 6==4.77 and protons of - g:3~ were observed in the form of quartet signal at 6==5.16 and in the form of doublet signal at 6==1.56. Protons of the end ester part were observed similarly as in usual esters. Chemical shifts, splitting mode and integral ratio of each signal satisfied those for each compound. The strongest base peak was commonly observed at m/e = 80 in their mass spectra. This strongest base peak at m/e = 80 was resulted from an ion expressed by the following formula: H\C _ C /CN H./ "‘ \.C+ H O In addition, a molecular ion peak M+ of each com- pound was observed though it was weak. Also fragment ion peaks of each compound, which could be guessed from the splitting mode of the above described struc—’ ture, were observed. 5 10 15 20 25 0127855 The absorption of 2240 cm-1 resulting from VC EN: the absorption of 1740 cm_1 resulting from VC==O, the absorption of 3135 cm-'1 resulting from “c -H (olefin) 1 resulting from “C =C and the absorption of 1620 cm- were commonly observed in IR-spectra. a-cyanoacrylate compounds according to the present invention is preferably synthesized by the reaction of the compounds expressed by the following general formula with formaldehyde products and then the thermal depolymerization of the resulting dehydrating conden- sation polymers: V NC-CH —c-0-121-c-0-122 2 H u 0 0 wherein R1 and R2 are same as the above described. Said compounds as raw materials expressed by the above described general formula are obtained by for example the dehydrochloric condensation reaction between cyanoacetic acid and chloroacetates or the dehydrating condensation reaction between cyanoacetic acid and lactates. Said formaldehyde products include formaldehyde and the substances producing formaldehyde in the reaction. However, paraformaldehyde is indust- rially important. - ; The reaction of said compounds as raw materials expressed by the above described formula with said 10 15 20 25 01 27855 formaldehyde products is carried out at a molar ratio of the latter calculated as formaldehyde to the former of for example 0.9 to 1.1 : l in the presence of suit- able basic catalysts, for example amines such as piperydine, ethanolamine and diethylamine or basic compounds such as alkaline metal hydroxide and alka- line metal alkoxide in suitable solvents; for example inactive solvents such as benzene, toluene, chloroform and trichloroethylene at 50 to 150°C, preferably 70 to 130°C to obtain dehydrating condensation polymers. The thermal depolymerization is carried out by washing the resulting compounds as raw materials with water or diluted aqueous solutions of acids and then heating under vacuum at 130 to 250°C, preferably 150 to 220°C in the presence of suitable depolymerization catalysts such as phosphorus pentoxide, phosphoric acid and condensed phosphoric acid. The novel a-cyanoacrylate compounds according to the present invention show a bonding performance to a substrate made of various kinds of material in the same manner as the known a-cyanoacrylate such as ethyl u-cyanoacylate and are effectively used as fast set- ting adhesives. The adhesives comprising the novel a-cyanoacrylate compounds according to the present invention are odorless or slightly give out fragrance 0127855 whereby being remarkably easy to handle in the prepar- ing process and the bonding process, producing no whitening in the bonding process, and improving the polymerization set products in brittleness. In addi- 5 tion, they are superior to the conventional u- cyanoacrylate in bonding strength to various kinds of substrate, for example metals, plastics, rubber, glass, wood and the like, particularly plated articles. It is perhaps owing to the chelate effect. Furthermore, the 10 adhesives comprising u-cyanoacrylate, in which R2 is allyl group (CHZCH = CH2), of the novel a-cyanoacrylate compounds according to the present invention have such an advantage that the substrate bonded therewith does not show a large reduction in bonding strength.even 15 when kept in a long time under the high temperature condition (for example one month at 150°C). In addi- tion, the adhesives according to the present invention are superior in bonding (i.e. joining, bleed—stopping) strength to tissues of living bodies such as skin, gum, 20 blood vessel and various kinds of organ and absorptivity into tissues after bonding. Additives such as radical polymerization inhibi- tors, anion polymerization inhibitors, plasticizers, tackifiers, coloring agents, fillers, diluents, water, 25 perfumes, carhoxylic acids, carboxylic anhydrides 10 15 20 25 0127855 and polyisocyanates may be added to the adhesives according to circumstances. The present invention is more particularly described and explained by means of the following Examples, in which "parts" and "%" are all by weight. EXAMPLE 1 325 parts of ethyl cyanoacetoxyacetate was added drop by drop to the mixture of 65 parts of paraform- aldehyde, 350 parts of toluene and 0.4 parts of pipery- dine put in a four—necked flask provided with a stirrer, a thermometer, a water-separating means and a dropping funnel with heating at 95 to 110°C and stirring. The reaction was continued with reflux-condensing to drive out the produced water. The stoichiometric amount of water was driven out within two hours and then the reaction mixture was cooled. After cooling the reac- tion mixture (condensation polymers) was washed with diluted aqueous solutions of acids and then toluene and water contained in the reaction mixture were distilled away under vacuum. Then the depolymerization was carried out by adding 4 parts of phosphorus pentoxide and 2 parts of hydroquinone and heating the resulting mixture under vacuum at l§0 to 200‘b to obtain 125 parts of the crude monomer. 82 parts of the purified monomer having a boiling point of 91 to 93°C/O.5mmHg was 0127855 -10.. obtained by distilling the mixture of the resulting crude monomer, a small amount of phosphorus pentoxide and a small amount of hydroquinone (0.3 %, respectively) under vacuum. According to a gas chromatography of its 5 solution diluted with nitromethane, the purity of the resulting purified monomer was 99 %. The yield was 23.4 %. The characteristics of the resulting monomer were as follows: 10 Thus it was confirmed that the resulting monomer was ethoxycarbonylmethyl a—cyanoacrylate (hereinafter reffered to as compound 1) expressed by the following formula: cm I-I\ I C=C—C-O—CH-C-0-CH -cu H’ a 2 u 2 3 o o 15 (molecular weight: 183) (1) 1H-NM spectrum is as shown in Fig. 1 (100 M2, CDC1 solvent, TMS internal standard). 3 20 Olefinic protons of'a—cyanoacrylate were observed in the form of single signal at 0 = 7.15 and 6 = 6.65. Protons of — CH2 — put between two ester parts were observed in the form of single signal at.6 = 4.77. (2) Mass spectrum is as shown in Fig. 2. 25 iThe strong peak resulting from a cation expressed 10 15 20 25 01 27855 _ 11 - by the following formula was observed at m/e = 80. H CN \C::C/ / H A molecular ion peak M+ was observed at m/e = 183. (3) IR-spectrum is as shown in Fig. 3. C EN Expansion and contraction vibration 2240 cm-1 C =0 Expansion and contraction vibration 1740 cm-1 C —H (olefin) Expansion and contraction vibration 3135 cm-1 1 C =C Expansion and contraction vibration 1620 cm- (4) Elementary analysis Measured value Theoretical value C (%) 52.66 52.46 H (%) 5.06 4.95 N (%) 8.06 7.65 (5) Boiling point 91 to 93°C/0.5 mmHg EXAMPLES 2 to 5 The compounds 2 to 5 as shown in Table 1 were obtain~ ed from paraformaldehyde and methyl cyanoacetoxyacetate, n-butyl cyanoacetoxyacetate, allyl cyanoacetoxyacetate or propargyl cyanoacetoxyacetate, which were the starting materials, in the same manner as in EXAMPLE 1. 10 15 20 25 0127855 _ 12 _ In addition, H-NMR spectrum, a mass spectrum and an IR-spectrum of the compound 2 of compounds shown in Table 1, that is to say methoxycarbonylmethyl a-cyanoacrylate (molecular weight : 169) is shown in Fig. 4, Fig. 5 and Fig. 6, respectively. Furthermore, 1H—NMR spectrum, a mass spectrum and an IR-spectrum of the compound 4 of compounds shown in Table 1, that is to say al1yloxy- carbonylmethyl a-cyanoacrylate (molecular weight : 195) is shown in Fig. 7, Fig. 8 and Fig. 9, respectively. Table 1 CN H I ‘c =:c — C — 0 — CH2 — C — 0 — R2 }{’ I! H 0 O Elementary analysis (%) C : H N -——n-- a9m 91°C/0.5 mm!-lg i 23:3: Com- pound 2 CH3 ll3'Vl15°C/0.5 mHg 101'U1O3°C/0.5 mHg wwx:-.c-a\o\.t>.t> III! O‘mO\\llUO|-‘N U'|DU'|\DOLAJ-vJkO 98 m1oo°c/0. 5 mmHg (Note) The upper numerical value shows the measured value while the lower numerical value shows the theoretical value in the results of element- ary analysis. 10 15 20 25 01 27855 _ 13 _ EXAMPLE 6 372 parts of ethyl 2—cyanoacetoxypropionate was added drop by drop to the mixture of 75 parts of para- formaldehyde, 350 parts of toluene and 0.5 parts of piperydine put in a four—necked flask provided with a stir- rer, a thermometer, a water-separating means and a dropping funnel with heating at 95 to 110°C and stirring. The reac— tion was continued with reflux-condensing to drive out the produced water. The stoichiometric amount of water was driven out within two hours and then the reaction mixture was cooled. After cooling the reaction mixture (condensation polymers) was washed with diluted aqueous solutions of acids and then toluene and water contained in the reaction mixture were distilled off under vacuum. Then the depolymerization was carried out by adding 5 parts of phosphorus pentoxide and 3 parts of hydroquinone and heating the resulting mixture under vacuum of 2 to 4 mmHg at 150 to 190°C to obtain 163 parts of the crude monomer. 122 parts of the purified monomer having a boiling point of 98 to 99°C/1 mmHg was obtained by distil- ling the mixture of the crude monomer, a small amount of phosphorus pentoxide and a small amount of hydroquinone (0.3 %, respectively) under vacuum. The purity of the resulting purified monomer was 98.6 %. The yield was 31.7 %. 10 15 20 25 0127855 -14- The characteristics of the resulting monomer were as follows: Thus it was confirmed that the resulting monomer was l-ethoxycarbonylethyl a—cyanoacrylate (hereinafter referred to as compound 6) expressed by the following formula: — C — O — CH -CH H u H O 0 (molecular weight: 197) (1) 1H-NMR spectrum is as shown in Fig. 10 (100 MHZ, CDCl3 solvent, TMS internal standard). Olefinic protons of a-cyanoacrylate were observed in the form of single signal at 6 = 7.15 and & = 6.65. in the form of doublet signal at 6 = 1.56. (2) Mass spectrum is as shown in Fig. 11. The strong peak resulting from a cation expressed by the following formula was observed at m/e = 80. H /CN :C:C\ + H C H O A molecular ion peak M+ was observed at m/e = 197. (3) IR—spectrum is as shown in Fig. 12. 10 15 20 25 0127855 - 15 _ C EN Expansion and contraction vibration 2240 cmul C =0 Expansion and contraction vibration 1740 cm_l C -H (olefin) Expansion and contraction vibration 3135 cm'1 1 C =C Expansion and contraction vibration 1620 cm- (4) Elementary analysis Measured value Theoretical value C (%) 54.92 54.82 H (%) 5.69 5.62 N (%) 7.17 7.10 (5) Boiling point 98 to 99°C/0.5 mmHg EXAMPLES 7 to 9 The compounds as shown in Table 2 were obtained from paraformaldehyde and methyl 2-cyanoacetoxypropio- hate, n—buty1 2—cyanoacetoxypropionate or allyl 2- cyanoacetoxypropionate, which were the starting materials, in the same manner as in EXAMPLE 6. 10 15 20 25 0127855 _ 15 _ Table 2 CN CH3 }{\ I I 2 C = C — C - 0 - CH ‘- C — O — R / H H H O 0 96 W 98°C/1 mmflg 1l4'V116°C/1 mmfig 105 "'l06°C/l mml-Ig (Note) The upper numerical value shows the measured value while the lower numerical value shows the theoretical value in the results of element- ary analysis. EXAMPLE 10 The compounds obtained in the above described EXAMPLE 1 and EXAMPLE 6 were tested on the performance as adhesives. Also ethyl a-cyanoacrylate was tested on the performance as adhesives for COMPARATIVE EXAMPLE. The results are shown in Table’3. 0127855 _ 17 _ Table 3 ' Ethyl 0- V Compound 1 Compound 6 Cyanoacr late F—-—-—-------—-—~———--—‘~*'"——-""-‘““"“‘-‘T‘“‘““‘”JL“““" Odor odorless Slightly giv— gciving out ’ing out frag- strong irritat- grance ing odor I whitening ‘ whitened all over the surface of Petri dish Set time (sec) Fe/Fe NBR/NBR Tensile shear 2 strength (kg/cm ) ; E Fe/Fe 153 3 sus/sus 162 I A1/Al 146 E Ni-plating/Ni- 152 ; 90 4o plating § Zn-p1ating/Zn- 173 § 130 120 , plating A ? § : ' I z ABS/ABS Adherend g Adherend Adherend E | failure . fa11UP€ failure § 5 - I 3 NBR/NBR Adhepend ? Adherend Adherend I ' failure ‘ failure failure Joining of liv- ing body ? ' E . 3 K Note 1. The odor was tested on the basis of sensual test by five panelers. Note 2. The Whitening of a drop of adhesives fallen in a Clean Petri dish was investigated after leaving for twenty-four hours at room tem- perature. _18_ 0127355 Note 3. The set time was measured in accordance with JIS K 6861. Note 4. The tensile shear strength was measured in accordance with JIS K 6850. Also the compounds 2 to 5 and 7 to 9 obtained in the above described EXAMPLES 2 to 5 and 7 to 9 were tested on the performance in the same manner as in the above described. The compounds 2 to 5 all were odor- 10 less while the compounds 7 to 9 all slightly gave out fragrance. The compounds 2 to 5 and 7 to 9 all did not produce the whitening. The compounds 2 to 5 and 7 to 9 all had the tensile shear strength of the same degree as the compound 1 or 6. They showed also the 15 desirable jointability to living bodies. In addition, an iron-piece/iron-piece bonded with the compound 4 (allyloxycarbonylmethyl u-cyanoacrylate) as adhesives was tested on tensile shear strength at higher temperature of 150'. The results are shown 20 in Table 4. However, COMPARATIVE EXAMPLE in Table 4 shows the adhesive of heat-resisting grade on the market which is obtained by adding aromatic carboxylic acids to ethyl u—cyanoacrylate. 25 It is found from this Table also that the com- 01 27855 _ 19 _ pound 4 is very effectively used as heat-resisting adhesives. Table 4 ; Compound 4 Tensile shear 2 strength (kg/Cm ) COMPARATIVE EXAMPLE At first After leaving for. 10 hours at 150°C After leaving for 7 days at l50°C__ After leaving for 15 days at 150°C After leaving for 29 days at 150°C _ 20 _ 0127855 what is claimed is: 1. a-cyanoacrylate compounds expressed by the follow- ing general formula: cu H I 5 ‘c=c—c-o-R‘-C-0-R2 H’ it ll 0 °cH .3 2 wherein R1 designates - CH2 - or - CH — and R desig- nates alkyl groups, alkenyl groups or alkynyl groups of C1 to C4. 10 2. A method of preparing a-cyanoacrylate compounds expressed by the following general formula: cm H I :c=-.c—c-0-R1-c-0-R2 H u u 0 OCH .3 15 wherein R1 designates - CH2 - or - CH - and R2 desig- nates alkyl groups, alkenyl groups or alkynyl groups of C to C4, comprising 1 a step for reacting the compounds expressed by the following genral formula: 20 NC-CH-C-Co—R1-C-O-R2 2 u .1 0 0 wherein R1 and R2 are same as the above described, with formaldehyde products; and a step for depolymerizing the resulting dehydrat- 25 ing condensation polymers. O1 2 7-8 55 -21.. 3. Adhesives comprising a—cyanoacrylate compounds expressed by the following general formula: H II ll 0 ‘EH3 wherein R1 designates - CH — or - CH - and R2 des1g- 2 nates alkyl groups. alkenyl groups or alkynyl groups of C1 to C4. I/Q 0127855 F|G.1 3(ppm>53 7 5 5 4 3 2 1 .0 2% 0127855 F|G.3 4000 3000 2(0) I500 IZW 8(1) (00 cm FlG.4 01 27855 2/e F|G.5 ‘Vlrlv !vt..$I. lt|u1.lD..v.!sr!.l.......%\n1tcs.|n :..2!6.tl.o.I.lIn1¢a..v..I\.||.Vn.....o». ..l§l. .. : F|G.6 400 1200 4000 7/5 0127855?’ FlG.7 FIG. 8 5'/é W ' 0127355 F|G.9 4000 3000 2000 1600 1200 . 800 400 FlG.1O 40(1) 3000 2000 FIG. 12 I600 [ZN BID o127855”“ mo -, EPO Form 1503. 03.82 E"',°°°a" Pam“ EUROPEAN SEARCH REPORT o1“‘%‘°Z""8"'§’-’”§°' FR-A-2 308 360 (ETHICON INC.) A 61 L 15/O6 * Page 20, lines 27-38; page 21, lines 1-10 * CHEMICAL ABSTRACTS, vol. 91, no. 7, 13th August 1979, page 646, no. 56325f, Columbus, Ohio, US; D.A. ARONOVICH et al.: "Carbalkoxymethyl esters of cyanoacetic and cyanoacrylic acids" & ZH. PRIKL. KHIM. (LENINGRAD) 1979, 52(4), 939-42 * Abstract * CHEMICAL ABSTRACTS SERVICE REGISTRY HANDBOOK, number section, part 1, 1978 supplement, page 958RG,American Chemical Society, Columbus, sEAHCHED(Int-CL’) Ohio, US; * Abstract 66470-71-1, "2-Propenoic acid, C 07 C 121/00 2-cyano-,2-methoxy-1-methyl—2-oxo ethyl ester, (S)-C8H9NO4" * FR-A-2 017 157 (MINNESOTA MINING AND MANUFACTURING CO.) * Pages 13-14 * Place of search Date of corn letion of the search Examiner THE HAGUE 07- 9-1984 VERHULST W. pl CATEGORY OF CITED DOCUMENTS : theory or princi e underlying the invention : earlier patent document. but published on, or : particularly relevant if taken alone after the filing date . : particularly relevant if combined with another : document cited in the application document of the same category : document cited for other reasons : technological background : non—written disclosure : member of the same patent family. corresponding : intermediate document document