2-Cyanoacrylates. Synthesis, Properties, and Applications

 Russian Chemical Re views 66 (I l) 953 — 962 (1997) - .._r.'.‘-.;_-..&..;_—_J_..n;.'__,.\._- © "1997 Russian Academy of Sciences and Turpion Ltd UDC 542.933:547.39l;S47.24l 2-Cyanoacrylates. Synthesis, properties and applications 7" Yu G G-ololobov, W Gruber Contents I. Introduction II. Methods for the synthesis of alley] 2-cyanoacrylates , Ill. Physical properties of 2-cyanoacrylrates IV. Chemical properties of 2-cyanoacrylic acid and its derivatives V. Prospects for the application ol“2-cyanoacrylates Abstract. Methods for the synthesis, properties and applications of allcyl 2-cyanoacrylates are surveyed. The reactions of alkyl 2-cyanoacrylales with various nncleophiles {thio1s, alcohols, diols, hydrogen sulfide. phosphines, etc.) including a new reaction involving insertion of isocyanates and lsothiocyanates into the C: C bonds in the adducts of alkyl 2-cyanoacrylates with trialkylphosphines are considered. The prospects for the use of alkyl 2~eyanoacrylates in organic synthesis, in the chemistry of polymers and in the chemistry of adhesives are described. The bibliography includes I i 7 references. I. Introduction Al‘-:Cl-lg5[CN)CGOE: + Ts}-E3 -——* Ea} _,__.. ref,’ C(CN)-COOEE _,q 3 rl " NH “N Ts’, N’ f 9”" *" F‘r3l°=l\'Ts + —r‘CH2—C 15 (E20051). 2). Reactions of 2-cyanoacryiates with nuclenphiles containing active hydrogen atoms When ACAS react with weak nucleophilcs, irrespective of the particular experimental procedure. conditions are created under which ACAS instantaneously‘ polymerise. However, when the nueieophile contains an active hydrogen atom, polymerisation of ACA is suppressed, because the primary adduct 6 is stabilised through self-protonaticn. .;: —. -C.t—t;=C(CN)(‘.0OR -= §*uCHactcNtcooii —— E" H H 6 --- NnCHgCH(CN)COOR. Supplied by The British Library - "The world's knowledge" The interaction of ACAs with thiols of diverse structures under conditions when excess thiol is present (which is achieved by adding the ACA to the reactions mixture) apparently gives rise to zwittcr—ion 16 in the first stage of the process. Since the proton at the sulfur atom in this zwitter-ion is relatively active, this species is rapidly self-protonated giving sulfide 17.7“ Dlthio- and thio-acids react with ACAS in a similar way. RS}.-1 + Cl-l;=C(CN)COOE1 = R$iCH25(CN)C0OEl ~—-- 'EI 16 —- RSCH2CH(CN}COOEt :7 R = Alk, Ar, HOCI-lgCH2, HSCH2CI-I2. HC1'NH2CHg, HCI-l‘-lH2Cl-i;Cl-l(COOH), HOOCCE-ig. Ac, {ETO)2P(S}, (Et0)2P(0)- Alcohols can be introduced in this reaction instead of thiols. Normally, alcohols cause only polymerisation of ACAS, because they are less acidic and less nucleophilic than thiois; however, under special conditions (in the presence of an acid the conjugate union of which is a weak nucleophile), formation of relatively stable adducts of ACAS with alcohols is possible. Unlike CAA, which reversibly adds water, its esters undergo instantaneous polymerisation in the presence of water. Treatment ofethyl cyanoacrylate with hydrogen sulfide in the presence of l % of Et3N gives aniinodihydrothlopyran 17 in a quantitative yield. N CODE‘: Et;N NH1 Cl-I;=C[CN)COOEt + H28 S / COOEt The interaction of AC;\s with phosphites 18a,b derived from pyrocatechol has been descrihed.5” The reaction gives rise to cyclic phosphonates 203,]: via the corresponding zwitzer-ions 19a,b {Scheme 6). Scheme 6 10%” CN Y = —cH;CH:— ta). 6- (b). In these case, too, the zwitter-ions 19n,h formed initially undergo self-protonationfi“ It should be noted that it is the formation of five-rnembered phosphorus-containing rings that ensures the success of the synthesis of monomeric products according to Scheme 6. When phosphites that cannot be con- vened into five-rnembered phosphoranes like 29 are used in this reaction, oligorneric derivatives are formed. c. Interaction of 2-cyanoacrylates with weal: nucleophiles in the presence of acids The zwitter-ions 6 formed initially in the reactions of weak nuclcophiles with ACAS can also be protonatccl by an acid present in the reaction mixture and forming no strong bonds with the nucleophile. In this case, the reaction yields salt 21. Yu G Gololobov, V Grubcr 958 Nu: - CH3“-‘C(CN)C0OR ———* Kucnzctcnqcook 335- 6 —~ .{luCl-I2Cl-l(Cl\')C0Ol{. X‘ 2: In this reaction, the acid not only protonates the zwitter-ion 6, but also activates ACA molecules. This has been confirmed by the data of IR spectroscopy?" according to which the nitrile and carboxyl groups in ACAs are protonated by acids, and this increases the overall eiectrophiiicity of the ACA molecule. The activating influence of acids ensures the murrence of reactions of ACAs with weak nucleophiles, which do not enter into these reactions without acids. Thus 1,3,2-benzodioxachloro- phosphole 23 does not react with ACAs in benzene a‘ 20 °C; however. when the reaction mixture contains CF3COOH, the process yields phosphor-late 24 (Scheme 7 .'-" Scheme’! 0 . '/ E :P--C1+CH1=C(CN)COOEt £530-95+ \ o 23 O\+ —- \ i ’!P—CH2CH{CN)COOEt _CFJC(O)C1 Oct cF3coo~ o / 0\ ll —- g I /P-CI-I:CH(CN}CO0Et. o - 24 This reaction is an example of conjugate addition of a weak nucleophile and a strong acid to an ACA; the proton of the acid acts as an inductor. Alcohols and other lowly nucleophilic reagents can also enter into these reactions.” ti. Interaction of 2-cyanoacrylates with C]-I-acids in the presence of bases In addition to P-, S- and O-nuclcophiles, C-nucleophiies (deriv- atives of CI-I-acids) can also add to ACAs under certain condi- tions giving rise to monomeric compounds {Scheme 3).” Scheme 8 B: + Ci-I:=C(Cl\’)CO0Et = iscnzércmcoost -3- lb 611 -—* Polymer, 3; + cnarxrr = in -.~ E:H(x)Y. 2s 25 énoov + Cl-i2=C(CN)COOEt =Y(x)CHc1-l25(CN>C00Et, 273 1'73 +1314. —- Y(x)CHCH;CH(CN‘JCO0Er + B: 2-: B: — amine; x = 1-1, COOR(R = I-LE1); Y - N01, CN, Ac. This version of the Michael reaction is possible only for those CI-l-acids that react with minor amounts of amines {present as catalysts of the reaction) much more rapidly than ACAS react with these amines. Thus, sufficiently basic amines (B) and relatlveiy strong Cl-I-acids with pK. < 13 (for example, 25) should be used. The acids should be rapidly converted into the conjugated bases 26, which would either cause polymerisation of the ACA or react with the ACA to give adduct 27-4. Thus, Scheme 8 reflects a fairly complex system of eouilibnum processes, the outcome of which Supplied by The British Library - "The world's know|edge" u ).,...,.........._......M. . -.,..._......_.....W.......,_.____......_.,.~,......a..w.. 4Yv\«~‘r4:-}'4’~Il“/‘MRI"V‘x‘1““*»v"‘4>b*"' M.......,s._....,.....s._-a._.u_..._.s.s..,.s..,..s...o..._..,..s..._. 2-Cyanoacrylates. Synthesis, properties and applications depends on the acidity of the Cl-I-acid, basicity of amine B. electrophilicity of the ACA, the nature of the solvent, tempera- ture and the order of mixing the reactants. The results obtained in the study cited 73 showed that the Michael reaction involving ACAS can be used as a general method for the synthesis of esters of substituted eyanocarboxylic acids. The method is suitable for the preparation of various functionally substituted compounds. V. Prospects for the application of 2-cyanoacrylates Although the intense development of the ‘monomeric’ chemistry of ACAs has started not long ago, it has led to two important consequences. On the one hand, the chemistry of ACAS has stimulated investigation of the chemical properties of the miller- ions '7 formed by AC!-ks and trialkylphosphines, and this has resulted in the discovery of the insertion of the carbamide fragment into the C—C bond (Scheme 5). This, in turn, stimu- lated the development of a new branch of catalysis, namely, intramolecular electrophiiic catalysis by a phosphoniurn centre. On the other hand, even the first studies on CAA and its esters provided grounds to expect that new ACAS would be synthesised, and this would markedly extend the performance characteristics of cold-setting adhesives and open up new ways for their use in industry, medicine and organic synthesis. 1. The ways to extend the temperature range of performance of adhesives based on 2-cyanoacrylates The strength of gluing surfaces together with an ACA depends on at least two factors. all other factors being the same, namely, the adhesive capacity of the cyanoacrylate itself and on the stability of the adhesive joint under the conditions of its performance (temperature, moisture content and hostility of the medium). industrially manufactured methyl and ethyl 2-cyanoacrylates forrn high-strength adhesive joints at room temperature; however, the stability of these joints at elevated {> 80- 100 “(D or low i: < -100 °C) temperatures is relatively low (especially in hostile or moist media). At the same time, ample experimental material on this topic implies that the temperature range of operation of cyanoacrylate adhesives have markedly extended, and their performance characteristics have improved. The relatively low stability of ACA polymers used under rigorous conditions can be explained by the fact that the polymer backbone contains a quaternary carbon atom (see Scheme 4). Polymers incorporating this fragment are known to possess low thermal stabilitles.“ Therefore, to increase the thermal stability of adhesive joints based on ACAs, the structure of the polymer backbone should be modified by introduction of fragments that would enhance the tolerance of the chain to high temperatures and hostile media (mostly water at various pH). The existing theoret- ical calculations 4- 75v 75 provide only general recommendations on the increase in the quality of adhesives based on ACAS. One of the possible ways of solving this problem is elaboration of cross-linked structures." Two approaches to the formation of ‘cross-linked‘ structures based on ACAs have been considered in the literature. One of them involves introduction of unsaturated carbon—carbon bonds into the ester fragment of ACAS; subse- quently, these bonds ensure cross-linking of the structure. Allyl and propargyl 2-cyanoacrylates as well as other esters of CAA containing more bullcy unsaturated groups have low viscosities; this is a necessary condition for attaining the inter- facial Contact between the adhesive and the substrate at the first stage of the formation of an adhesive joint.”-45v75‘3° Under the action of traces of moisture or other active reagents, the C=C bond of the aerylate is cleaved on the surfaces being glued together.”-9‘ Study on the thermodynamics of polymerisation of ailyl cyanoacrylate and allyloxyethyl cyanoacrylategi makes it possible to conclude that at room temperature these monomers are completely converted into the corresponding polymers by an 959 anionic mechanism, and above l0O “C, cross-linked structures are formed as a result ofrupture ofthe multiple bonds in the ally} and propargyl fragrnents.‘“5- 75v 79- 33 it has been noted 3‘ that the inter- faciai interaction between substrate and adhesive is due to van der Waals and dipole—dipole forces. In addition to these adhesive forces, chemical bonds of various natures (adsorption theory of adhesion) contribute to the interaction.“ It is noteworthy that, whereas the C=C bond of the acrylatc is cleaved by an anionic mechanism, rupture of multiple bonds in the ester fragment of the molecule occurs only with the participation of free radicals.” As a result, an adhesive joint based on unsaturated esters of CAA possesses better performance characteristics than a similar joint based on saturated deriv2.tives.“5- 5* The main drawback of cross- iinked structures based on unsaturated 2-cyanoacrylates (regard- ing their practical use) is that in this case, strengthening of adhesive joints occurs only at elevated temperatures {> 100 “C). However. it is often necessary that joints be strengthened below 100 “C. In addition, this procedure can yield a rigid cross-linked polymer and, consequently, the adhesion layer can become brittle.” Elastomers can be partly dissolved in ACA5 during gluing to give interpenetrating networks 57 (the process is described in terms of the diffusion theory of adhesion). The second approach to the production of a cross-linked adhesive layer is based on copolyrnerisation of methyl or ethyl cyanoacry- lates with unsaturated compounds of various types. Apparently, by selecting an appropriate cornonomer, one can obtain adhesive joints with properties varying over a wide range. This approach is more advantageous, because in some cases, a ‘cross-linked’ adhesive joint can be obtained at low temperatures. Unsaturated compounds containing electronegative polar groups have been used as comonomers, because, on the one hand, owing to these groups, compounds enter in the copolymerisation with ACAS and, on the other hand, these substituents ensure additional cohesion with the substrate. This line of research has led to impressive progress.3"" """"’5 Evidently, the structure of 2-cyano- acrylates derived from diols 37 and triols9‘ is nearly ideal, because in these cases, a cross-linked adhesive joint is formed rapidly under conditions close tci those used 1' or the polymerisation of the main monomer. Unfortunately, at present, it is fairly difficult to produce bis- and Iris-cyanoacrylatcs in large amounts. Some methods proposed for their synthesis 3“= 37 are labour-consuming and expensive; direct esterification of CAA 4‘ '43 or its chloride as well as transesteriilcation of methyl cyanoacrylate with diols39 can be used only on a laboratory scale. Judging by several publica.ti0ns.77'97‘ W3 the research aimed at the involvement of esters of 2-cyano-2.4-pentadienoic acid in the copolymerisation with ACAS is proceeding vigorously. The derivatives of ethylene glycol and 2-cyano-2,4-peutadienoic acid are especially efficient? These esters polyrnerise at room tempera- ture in the presence of the same catalysts that induce polymer- isation of ACA to give a cross-linked structure. It has been shown 7'"-9'-' that the performance characteristics of ACAS are markedly improved when they are used as mixtures with buta- disne derivatives. These cross-linking reagents are synthesised by the K.n5vena- gel reaction between the corresponding esters of cyanoaoetic acid and aldchydes (Scheme 9).”-99 Scheme 9 ZnCl Cl-l2(C:\l}COOEt + R’CH=Cl-lCi-10 j‘ :"' R'CH=CHCH=C[CN'JCO0El R’ = H, Me. A significant feature of the process shown in Scheme 9 is that anhydrous zinc chloride dissolved in dioxane or THF is used as the catalyst. A method 1' or the synthesis of bis-2-cyanopentadienoates derived from diois containing disiloxane units in the chain has been recently described in a patent.‘-03 Supplied by The British Library - "The world's knowledge" 'r r" —-r————~- --~ v--—~.... .........-.,.. r,....,_,,_,_,_,_ Cm them and thus fix any traces left there, for example, finger. prints. l '7 439 {"1935} 37'. C 5 Buck J’. Polym. Sci. 16 2475 (i978) Supplied by The British Libraiy- "The world's knowledge" Yu G Goiolobov. V Gruber 960 2. The use of 2-cyanoacrylates in medicine The ability of ACAs to polyrnerise on the surface of a living tissue over periods of several seconds under very mild conditions without special initiation permits these compounds to be regarded as promising surgical materials.“‘4 it is of prime importance that the polymer based on an ACA is destroyed relatively quickly in a Eiving organisrn.‘°5 Polymers based on isobutyl and isoamyl cyanoaerylates are highly biocornpatible. It should also be mentioned that ACAs are relatively non-toxic and possess antimicrobial activities. l,2-isopropylidencglyceryl cyanoacrylates are quite promising in this respect.” Laboratory and clinical tests on the regeneration of tissue cells and restoration of other characteristics of an organism have shown that ACAs ensure strong and elastic connection of tissues; simultaneously, they exhibit antiseptic properties and pose no harmful conse- quences. ‘95 Medical adhesives of this type are used during surgical operations on lungs. brains, heart, kidneys, on organs of diges- tion, sight and respiration, bone tissue and teeth.“-‘°““°9 Efficient medicinal adhesives of the MK series and SO-9m, SO-9t and SO-57 trademarks prepared using fluorinated meth- acrylates as conionorners have been developed in the former USSR by Russian, Ukrainian and Azerhaijanian chemists. These forrnuiations are non-toxic and tolerant to disinfectants.“ They possess bacteriostaric and bactericide properties; besides, they are biodegradable in an organism and Form no toxic products of decomposition. They also cause no immunological reaction.“ The second way of using ACAS in medicine is associated with the development of medical preparations of prolonged action based on them. A procedure has been elaborated for incorporat- ing medical preparations into an ACA-based polymeric matrix. When an ACA is introduced into an intensely stirred solution ofa drug, it polymerises to give particles with a size of l70—350 nm containing molecules of the drug sorbed in the poiymenc matrix. This procedure was used to obtain immobilised apornorphine "'3 and oxytocin. ' 13 The procedure is general and, apparently, it can be used in several ‘variants. 3. Other applications of 2-cyanoacrylates Polymers based on ACAS are used to produce photo- and electrono-resists. By chemical deposition of perfluoroethyl cyano- acrylate vapour on a support, a photoresist with a sensitivity of‘ 0.2 J crrr‘ has been obtained.“ Positive electronoresists have been obtained using hornopolymers of ACAs and their copoly- mcrs with functionally subszituted :nonomers.’°5 Lengthening of the hydrocarbon chain in the ester group of ACAS markedly decreases the adhesive properties of these compounds. Alltyl cyanoacrylates in which the alicyi chain consists of more than six methylene units have found application in the formation of Lar.gmuir—Blodgett monomoiecular layer5.l ‘5 Monolayers are formed by polymerisation cl‘ CAA esters (from hexyl to decyl ester) directly on the water surface. Since the energy of interaction of the cyano-group in the polymer with water is relatively low (14.6 kl), the monolayer can be easily transferred on a solid support. At the same time, monornoleculat layers of poly(alltyl cyanoacrylates) exhibit some adhesion both to hydrophilic and to hydrophobic surfaces. The above technology for the preparation of Langrnuir—Blodgett films can be used in the production of micro-instruments by the submicron technology. Cyanoacrylates are readily soiuble in liquid carbon dioxide? ‘ 5 therefore, ACAS packed in aerosol bottles can be used in those cases where a high concentration of ACA vapour is needed. It is clear that the aerosol use or" ACAs would help to solve some unexpected problems, because it would permit almost instanta- neous production of a polymeric adhesive surface on various objects. ACA vapours deposited on various surfaces polymcrise on them and thus fix any traces left there, For example, finger- prints.” Supplied by The British Library - 1k fir if: The data presented in this review provide grounds for believing that at present, a new stage in the development of the chemistry of ACAs has started. This can lead to development of cold-setting adhesives with better performance properties; in addition, new applications of CA:-\ derivatives can appear, and the use of ACAs in organic and organometallic synthesis can become wider. The review was prepared with the support of the Russian Foundation for Basic Research (Project No. 95-O3-08200). References 1. US P. 2 467 926; Chem. Ahsrr. 43 6222 (1949) 2. US P. 2 '.r'2’.l 858 (£955) 3. .\J Lee C yariaacrylare Resirti — the Jmram Ac.lhe.rt've.r (Pasadena: Pasadena Technology Press, 1931) 4. L M Pr-itylvcin, D A Kardashov, V ‘L Valcula Monomer-n_ve Kiel‘ (Monomeric Adhesircsj (Moscow: Khimiya, i988) Y Okarnoto, P T Klerrtarczylr. J. Aa'Fie.v. 4031 (1993) J Y Yang, A Garton J. Appl. Palym. Sci‘. 48 359 (1993) N N Trolirnov. D A Aronovich, V S Etlls, M Pinchuk P.'mnna:.ty (9) 55 (1976) 8. K L Shantha, S Thennarasu, N Krishnamurti J. Adhes. Sci‘. Techno]. 3 237 (1989) 9. J M Rooney Polym. J. (3) 975 (1981) I0. BRD P. 3 415 181 ; Cfrem. Absrr. 104 £48 334 (1986) 11. Yu G Goiolobov, T O Krylova Her. Chem. 6 271 (1995) l2. Yu G Gololobov, G D Koiornnilcova, 1'' O Krylova Zh. Obsizcli. ."(him. 64 4| l (1994) i3: M Yonezawa, S Sumki, H Ito, K. Ito Yukifioseikugnfcu Kyoknirhi 25 31] (I967) l-4. K G Cborbadjiev, P Ch Novakov Eur. Poiym. J. 27 439 (1991) 15. Yu H Voitekurias, Ya N Pirig Kiner. Kata}. 33 W74 (1992) 5 16. D C Pepper, C Blrkinsltou Polym. De-grad. Stab. I6 24] (I986) 17. J M Rooney Br. Polym. J’. 13 I60 (1931) i8. K G Chorbadjiev, P Ch Novaltov Eur. Palym. .!.271009 (1991) 19. T Matsumoto, K C Pani, R M Hardawsy. F Leonard Mil’. Med. 13 2515 (1967) 20. H .la[‘t”e, C W R Wade. A F I-legyeli, R M Rice. 3 Hodge J. .3t'on-ted. Mater. Res. 20 2 I7 (1986) 2]. N G Senchcnya, N V Sergienlro, K A Mtiger, L I Makurova, T I Guseva. A A Zhdanov, Yu G Gololobov Jzv. Akad. .-‘\v’aur’c, Ser. Khim. 949 U995)“ 22. T l Guseva, Ix’ G Senchenya, K A Mager, V A 'l'syryapl