Reactive Polymers Fundamentals and Applications

Home , Cyanoacrylate, Ethyl cyanoacetate, Ethyl cyanoacrylate

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Cyanoacrylates were commercially introduced in for polymerization. Instead of aqueous formaldehyde, 1950 by Tennesee Eastman Company. Cyanoacrylate paraformaldehyde was used with an organic solvent to adhesives are monomeric adhesives. They are gener- remove the water by azeotropic distillation. The sta- ally quick-setting materials which cure to clear, hard bility of the monomer can be enhanced by the redistil- glassy resins, useful as sealants, coatings, and par- lation of the crude monomer in the presence of small ticularly adhesives for bonding together a variety of quantities of acidic stabilizers, e.g., sulfur dioxide. substrates [1]. Polymers of alkyl 2-cyanoacrylates are Several other methods for cyanoacrylate monomer also known as superglues. production have been described, including the pyro- In addition to their use as adhesives, cyanoacrylates lysis of 3-alkoxy-2-cyanopropionates [8], transester- have been reported to have highly herbicidal prop- ification of ethyl cyanoacrylate [9], and displacement erties, as they disrupt photosynthetic electron trans- of cyanoacrylate monomer from its anthracene Diels- portation [2–4]. Alder adduct by treatment with maleic anhydride. This last method is used for the synthesis of monomers 13.1 Monomers that are not accessible or may be difficult to prepare by the retropolymerization route, for example difunc- 13.1.1 Synthesis tional cyanoacrylates [10], thiocyanoacrylates [11], and perfluorinated monomers. In 1895 von Auwers and Thorpe [5] attempted to synthesize diethyl-2,2-dicyanoglutarate (Figure 13.1) by base-catalyzed condensation of aqueous formalde- 13.1.2 Crosslinkers hyde and ethyl cyanoacetate. They isolated a mixture To improve the cohesive strength, difunctional mono- of oily oligomers and an amorphous polymer of higher meric crosslinking agents may be added to the mono- molecular weight. mer compositions. These include alkyl bis(2-cyano- In fact, ethyl cyanoacrylate monomer was synthe- acrylates), triallyl isocyanurates, alkylene diacrylates, sized as an intermediate, which underwent an imme- alkylene dimethacrylates, trimethylol propane triacry- diate polymerization reaction. The condensation of late, and alkyl bis(2-cyanoacrylates) [15]. formaldehyde with cyanoacetate is still the most important method for the commercial production of the 13.1.3 Commercial Products monomers, cf. Figure 13.2. The reaction mechanism takes place as a base-catalyzed Knoevenagel conden- Commercial products consist mainly of monofunc- sation of cyanoacetate and formaldehyde to give an tional monomers. Commonly encountered monomers intermediate disubstituted methylol derivative. are shown in Table 13.1. The monomers are usually A.E. Ardis [6] at B.F. Goodrich (in 1947) found low-viscosity liquids with excellent wetting proper- that the polymer-oligomer mixture obtained in ties. The basic structure of cyanoacrylate monomers the formaldehyde-cyanoacetate condensation reac- and polymers is shown in Figure 13.3. The syntheses tion could be thermally depolymerized with acid cat- of the monomers and the raw materials are shown in alysts. However, the monomer prepared by utilizing Figures 13.4 and 13.5. Because of the high electro- these methods was unstable and the yields were low. negativity of the nitrile group and the carboxylate Later [7] it was realized that the water is responsible

CN CN CN CN CN H C H CH2 C CH O + CH C H C CH C H 2 COR 2 2 C OR-H2O CO R R O C C OR O O O O O Figure 13.2 Synthesis of cyanoacrylates: Knoeve- Figure 13.1 2,4-Dicyanoglutaric acid ester. nagel reaction.

318 REACTIVE POLYMERS FUNDAMENTALS AND APPLICATIONS

Table 13.1 Commercially Available Cyanoacrylates

Compound Remarks Methyl cyanoacrylate Strongest bonding to metals, good stability against solvents Ethyl cyanoacrylate General purpose Allyl cyanoacrylate >100 ◦C service temperature n-Butyl cyanoacrylate Flexible, medical applications [12] Isobutyl cyanoacrylate Medical applications [12] 2-Octyl cyanoacrylate Medical applications [13,12] 2-Methoxyethyl cyanoacrylate Weak odor 2-Ethoxyethyl cyanoacrylate Weak odor 2-Methoxy-1-methylethyl cyanoacrylate Weak odor Methacryloyloxyethyl-2-cyanopenta-2,4-dienoate Strong adhesive [14]

CN CN Cl Cl CH C CH2 C CC CH CO H 2 n 3 COR COR H Cl O O O H2 O Cl2 Figure 13.3 Basic structure of cyanoacrylate monomers and polymers.

Cl CH2 CO H O CN Figure 13.5 Synthesis of chloroacetic acid. ++H C H CH2 O C OR N O H CN CN CCH - - 2 Y CH C Y + 2 C O R C O R -H2O O O

CN N N N CH2 C H C C C OR Y CCH - 2 Y CH2 C O OC R C O R - O O Figure 13.6 Resonance structures of the growing anions.

CN CH C 2 in this way exhibit high molecular weights, usually COR more than 106 Da. O Figure 13.4 Synthesis of cyanoacrylates: Mannich reaction. 13.2 Special Additives groups, they undergo rapid anionic polymerization on 13.2.1 Plasticizers contact with basic catalysts. The anionic polymeriza- Adhesives based on cyanoacrylate esters are effective tion is facilitated by the possibility of resonance struc- bonding agents for a wide variety of materials, but do tures, as shown in Figure 13.6. The polymers formed not give a permanent bond in joints involving glass. Propery of Reed Elsevier

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A strong bond to glass is obtained initially but gener- Table 13.4 Comonomers and Polymeric Additives ally the joint fails after a period of weeks or months Compound Reference at room temperature conditions. The extremely rapid curing rate on glass caused by the basic nature of the Methacrylate oleﬁn copolymer [18] Short-chain alternating acrylic copolymers [19] surface is responsible for high stresses that are gener- Polyester from aliphatic/aromatic acids [20] ated in the bond line immediately adjacent to the glass, Elastomer from a core-shell polymer [21] at a molecular level. These stresses make the polymer Acrylate [22] in the bond line uniquely susceptible to chemical or physical degradation [16]. tion of plasticizer needed for good durability is about Cyanoacrylate adhesive bonds also tend to be rela- 30–50%. tively brittle; therefore, the adhesive compositions are Also, comonomers for cyanacrylate polymers and often plasticized [17]. Typical plasticizers include var- polymeric additives have been described as plasticiz- ious alkyl esters and diesters and alkyl and aromatic ers. These are listed in Table 13.4. phosphates and phosphonates, diallyl phthalates, and Components that may form semi-interpenetrating aryl and diaryl ethers. Plasticizers are summarized in polymer networks are based on poly(ethyl-2-cyano- Table 13.2. acrylate) and an oligo(ethylene glycol) diglycidyl For glass bonding, dibutyl phthalate is a suitable ether. These formulations were developed to reduce plasticizer in n-butyl cyanoacrylate [16]. The glass the brittleness of neat poly(cyanoacrylate)s [23]. bonds were tested for durability by subjecting them Some of these materials were found to be transpar- to a sequence of washing cycles in a domestic dish- ent and exhibited great ﬂexibility, which was main- washer. The results shown in Table 13.3 suggest that tained after 24 h of immersion in water and subsequent the bond strength decreases with increasing propor- drying. tions of plasticizer. Levels greater than about 40% result in bonds of reduced strength. The concentra- 13.2.2 Accelerators The esters of 2-cyanoacrylic acid are also com- Table 13.2 Plasticizers [15] monly called quick-set adhesives, since they generally Compound Compound harden after a few seconds when used or the joined Dioctyl phthalate Dimethyl sebacate parts exhibit at least a certain degree of initial strength. Triethyl phosphate Tri(2-ethylhexyl)phosphate However, in the case of some substrates, especially Tr i(p-cresyl)phosphate Glyceryl triacetate acidic substrates such as wood or paper, the polymer- Glyceryl tributyrate Diethyl sebacate ization reaction may be very greatly delayed. Dioctyl adipate Isopropyl myristate Acidic materials exhibit a pronounced tendency to Butyl stearate Lauric acid Dibutyl phthalate Trioctyl trimellitate draw the adhesive, which is often highly liquid, out of Dioctyl glutarate the joint gap by capillary action before hardening has taken place in the gap. Even in cases in which, for reasons of geometry, the Table 13.3 Durability of Bonds to Glass with Various adhesive must be applied in a relatively thick layer Amounts of Plasticizer [16] in the joint gap or in cases where relatively large Dibutyl Phthalate Bond Strength Durabilitya amounts of adhesive are applied and relatively large (%) (N mm−2) drops of adhesive protrude from between the parts to 02.705be joined, rapid hardening throughout may rarely be 10 3.20 3 achieved [24]. 20 3.20 5 Therefore, attempts have been made to accelerate 25 1.94 5 the polymerization for such applications by means of 30 2.46 50 certain additives. The methods used may roughly be 40 1.86 90 50 0.80 90 divided into three categories: 60 0.32 20 70 0.08 10 • Addition of accelerators directly to the adhesive a Number of Dishwasher Cycles. formulation. This is possible to only a very limited Propery of Reed Elsevier

320 REACTIVE POLYMERS FUNDAMENTALS AND APPLICATIONS

extent, however, since substances having a basic or nucleophilic action, which would normally bring R1 about a pronounced acceleration of the polymer- (CH2 CH2 O)n Si O

ization of the cyanoacrylate adhesive, are generally R2 used at the expense of the storage stability of such compositions. n = 4...10 • The second common method is the addition of the Figure 13.7 Silacrown ethers [25]. accelerators shortly before application of the adhesive in virtually a two-component system. How- 13.2.2.2 Calixarenes ever, this method has the disadvantage that the working life is limited after the activator has been Cyanoacrylate adhesive compositions that employ mixed in. In addition, with the small amounts of calixarene compounds as additives give substantially activator that are required, the necessary accuracy reduced fixture and cure times on wood and other of metering and homogeneity of mixing are diffi- deactivating surfaces such as leather, ceramic, plas- cult to achieve. tics, and metals with chromate-treated or ceramic oxide surfaces [29–31]. • A third process is the use of activators in the form of a dilute solution. The solution is sprayed onto the 13.2.2.3 Amines parts before they are bonded onto the places where the adhesive is still liquid after the substrates have Solutions of lower fatty amines, aromatic amines, and been joined. The solvents used for such dilute solu- dimethylamine are used that are sprayed on the sur- tions of activators are generally low-boiling organic face before the cyanoacrylate is applied, or at the solvents. same time. Examples are N,N-dimethylbenzylamine, N-methylmorpholine, and N,N-diethyltoluidine. N,N-Dimethyl-p-toluidine, when subsequently Cure accelerators include crown ethers, calixarene applied to the joined parts, causes even relatively compounds, silacrown compounds, and amines. large amounts of adhesive to harden within seconds. The poly(cyanoacrylate) so formed is completely free of turbidity. Disadvantages include the very high 13.2.2.1 Silacrown Compounds volatility of the substance, which does not permit Silacrown compounds as additives give substantially long waiting times between the application of the reduced fixture and cure times on wood and other accelerator solution to the substrates to be bonded deactivating surfaces such as leather, ceramic, plas- and the subsequent bonding process. The compound tics, and metals with chromate-treated or acidic oxide is also toxic [24]. surfaces. Silacrown accelerators have significantly lower 13.2.2.4 Disulfides reported acute toxicity than the crown ether com- Examples of disulfides are dibenzodiazyl disulfide, pounds. The lower observed toxicity of silacrowns 6,6 -dithiodinicotinic acid, 2,2 -dipyridyl disulfide, or in comparison to crown ethers may be related to the bis(4-tert-butyl-1-isopropyl-2-imidazolyl) disulfide hydrolytic instability of the Si–O–C linkage. Thus, [24], cf. Figure 13.8. The disulfides have a good accel- while the silacrown ring is stable in the cyanoacrylate erating action, but they nevertheless permit a long composition, it will open up in biological environ- waiting time between application of the activator and ments, reducing both acute and chronic risk [26]. application of the adhesive. In addition, they avoid Silacrowns are prepared by transesterification of spontaneous, merely superficial hardening. alkoxysilanes with poly(ethylene glycol)s (PEGs), i.e., they are reaction products of silanes but are not themselves silanes. Silacrown compounds are 13.2.3 Thickeners commercially available and are reportedly readily Thickeners are added to increase the viscosity of 2- synthesized in good yield [25–28]. Silacrown ethers cyanoacrylate adhesive compositions. The 2-cyano- are shown in Figure 13.7. acrylate monomer generally has a low viscosity of Propery of Reed Elsevier

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NN 13.2.4 Stabilizers SS Stabilizers have to be added both for the production and for storage. The stabilizer systems are added so NN that no polymerization occurs during transportation HOOC SS COOH and storage in sealed drums, even at elevated temper- atures and after long periods. After application polymerization occurs immediately. Accordingly, besides radical polymerization

N N inhibitors, inhibitors against anionic polymerization SS are generally added to cyanoacrylate adhesives. Sta- N N bilizers are summarized in Table 13.6. A typical stabilizer to prevent radical polymer-

ization is hydroquinone. Boron trifluoride prevents Figure 13.8 2,2 -Dipyridyl disulfide, 6,6 -dithiodinico- anionic polymerization. tinic acid, and bis(4-tert-butyl-1-isopropyl-2-imidazolyl) disulfide. 13.2.4.1 Acidic Cation Exchanger It has been proposed to add a strongly acidic cation Table 13.5 Thickeners exchanger as inhibitor. Cation exchangers are based on crosslinked poly(styrene)-containing sulfonic acid Compound Reference groups. Fumed silica [26] The disadvantage of this approach is that the ion Poly(cyanoacrylate) [15] Poly(lactic acid) [15] exchanger added can easily impede the outflow of the Poly(glycolic acid) [15] adhesive and that, as a solid, it does not act throughout Lactic-glycolic acid copolymers [15] the entire volume of the adhesive. Poly(ε-caprolactone) [15] Poly(3-hydroxybutyric acid) [15] Polyorthoesters [15] 13.2.4.2 Acid Groups on Container Polyacrylates [15] Walls Polymethacrylates [15] It has been proposed to modify the surface of storage containers for cyanoacrylate adhesives in such a way that they contain acid groups [32]. Although this pro- posal can be successfully implemented, it is afflicted several centipoise, and therefore the adhesive pene- by the problem that the inhibition occurs in the vicin- trates into porous materials such as wood and leather ity of the container wall. or adherents with a rough surface. Thus, good adhesion bond strengths are difficult to achieve. Thickeners 13.2.4.3 Sulfur Compounds are summarized in Table 13.5. Various polymers can be used as thickeners, and Sulfur Dioxide. Another method of stabilizing examples include poly(methyl methacrylate), metha- cyanoacrylate adhesives is to add sulfur dioxide as crylate-type copolymers, acrylic rubbers, cellulose an inhibitor. Although this measure has been success- derivatives, poly(vinyl acetate), and poly(2-cyano- fully applied in practice, it is important to bear in mind acrylate). A suitable amount of thickener is generally that sulfur dioxide is a gaseous substance and that uni- about 20% by weight or less based on the total weight form addition is difficult so that quality variations can of the adhesive composition. occur. In addition, sulfur dioxide can escape from the Fumed silica for use as thickener is treated with adhesive containers by diffusion during storage. poly(dialkylsiloxane) or trialkoxyalkylsilanes [26]. The purpose of the silane which is retained on the Dioxathiolanes. Cyclic organic sulfates, sulfites, surface of the silica is to maintain the fumed silica in sulfoxides, and sulfinates, for example 2-oxo-1,3,2- a dispersion within the composition. dioxathiolanes, act in raising the ceiling temperature Propery of Reed Elsevier

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Table 13.6 Stabilizers

Compound Reference Sulfur dioxide [15] 6-Hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid [15] Lactone [15] Boron trifluoride [15] Hydroquinone [15] Catechol [15] Pyrogallol [15] p-Benzoquinone [15] 2-Hydroxybenzoquinone [15] p-Methoxyphenol [15] tert-Butylcatechol [15] Organic acid [15] Butylated hydroxyanisole [15] Butylated hydroxytoluene [15] tert-Butyl hydroquinone [15] Alkyl sulfate [15] Alkyl sulfite [15] 3-Sulfolene [15] Alkyl sulfone [15] Alkyl sulfoxide [15] Mercaptan [15] Alkyl sulfide [15] Dioxathiolanes [33]

and hence to improve the thermal stability of the treatments include corona discharge exposure of the adhesives [33]. substrate surface, acid etching, plasma treatment, etc. 4,5-Dimethyl-2-oxo-1,3,2-dioxathiolane is a liquid However, these methods are clearly not applicable to with a boiling point of 185 ◦C. This is an inhibitor for the bonding of plastic substrates in the domestic or the anionic polymerization and should be effective household areas. Alternatively, various primer com- throughout the entire volume of the adhesive. It can positions have been developed which are designed to be added more uniformly and more easily than gases. be applied to the plastic substrate to be bonded prior In addition, the discoloration of the adhesive during to application of the adhesive [35]. Primers contain storage is prevented [34]. mostly aminic structures. Some primers are listed in Table 13.7. 13.2.5 Primers 13.2.6 Diazabicyclo and It is well known in the adhesive field that there are plastic substrates made from certain types of plastic Triazabicyclo Primers materials which are extremely difficult to bond. Such 1,5-Diazabicyclo[4.3.0]non-5-ene, 1,8-diazabicyclo- difficult-to-bond materials include low surface energy [5.4.0]undec-7-ene, and 1,5,7-triazabicyclo[4.4.0]dec- plastics such as poly(ethylene) and poly(propylene) 5-ene are shown in Figure 13.9. It is well known that and highly crystalline materials such as polyac- solutions of amines and other organic and inorganic etals and poly(butylene terephthalate). As a conse- bases will accelerate the curing of cyanoacrylate adhe- quence of the difficulty in bonding substrates made sives. Diazabicyclo and triazabicyclo compounds also from these plastics materials with adhesives, various confer adhesion to nonpolar substrates [36,37]. surface treatments have been employed where such This primer acts in a two-component adhesive sys- materials require bonding. Examples of such surface tem comprising 2-cyanoacrylate adhesive and the Propery of Reed Elsevier

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Table 13.7 Primers

Compound Reference n-Octylamine [38] 1,5-Diazabicyclo[4.3.0]non-5-ene [36,37] 1,8-Diazabicyclo[5.4.0]undec-7-ene [36,37] 1,5,7-Triazabicyclo[4.4.0]dec-5-ene [36,37] Tetra-n-butyl ammonium ﬂuoride [39,40] Tributylphosphine [41] N,N,N,N-Tetramethylethylene diamine [35] N,N,N,N-Tetraethylethylene diamine [42] N,N,N,N-Tetramethyl-1,3-butane diamine [35] N,N-Dimethyl-N,N-di(2-hydroxypropyl)-1,3-propane diamine [35] N-2-Aminoethyl-3-aminopropyl-tris(2-ethylhexoxy)silane [35] Imidazole derivatives [43] 2-Phenyl-2-imidazoline [43] Organometallic compounds [44] Manganese(III) acetylacetonate [44]

H NH2 N N N N CH2

CH2 H N N N N CH2 CH2 NH2 + OC (CH2)10 CH3 Figure 13.9 1,5-Diazabicyclo[4.3.0]non-5-ene, 1,8- CH diazabicyclo[5.4.0]undec-7-ene, and 1,5,7-triazabi- 2 cyclo[4.4.0]dec-5-ene. CH2

NH2 azabicyclo primer. In poly(propylene) the application of 1,8-diazabicyclo[5.4.0]undec-7-ene, the tensile shear bond strength increases to 74 kg cm−2 in com- NH C(CH) CH parison to 7 kg cm−2 without primer. 2 10 3 CH2 CH 13.2.7 Polyamine Dendrimers 2 N CH2 CH2 NH C(CH2)10 CH3 Compounds with a variety of highly branched archi- CH2 tectures are known, including cascade, dendrimer, CH hyperbranched, and comb-like architectures. The 2 term multi-amine compounds refers to compounds NH C (CH2)10 CH3 with such branched architectures in which branching Figure 13.10 Condensation of tris(2-aminoethyl)- occurs via tertiary amine groups. amine and dodecyl aldehyde [45]. For example, polyamine dendrimers are prepared by the condensation of tris(2-aminoethyl)amine and substrate and will give effective bonding improvement dodecyl aldehyde followed by reduction with tetra- on polyoleﬁn substrates. n-butylammonium cyanoborohydride [45]. The reaction is shown in Figure 13.10. The contact between the adhesive and the multi-amine compound may 13.3 Curing be accomplished by mixing immediately prior to bonding. Ordinarily, however, using the multi-amine Cyanoacrylates can be polymerized both by radical compound in a primer composition will provide and by anionic mechanisms. The polymerization the most practical and convenient application to the of cyanoacrylates has been monitored by Raman Propery of Reed Elsevier

324 REACTIVE POLYMERS FUNDAMENTALS AND APPLICATIONS spectroscopy [46]. Cyanoacrylates polymerize Ferrocene and DAROCURTM 1173 (2-hydroxy- comparatively slowly with free-radical initiators. 2-methyl-1-phenyl-1-propane) are photocatalysts However, in the presence of catalytic amounts of suitable for cyanoacrylates [48]. Radiation times of anionic bases and in the presence of covalent bases 5–15 s are sufficient. such as amines and phosphines, they polymerize Acryloyloxyethyl-2-cyanopenta-2,4-dienoate is extremely rapidly. polymerized by heat or moisture, as well as by UV The exceptionally fast rate of anionic polymer- light [14]. UV light curable compositions have been ization of cyanoacrylates in the presence of a base, prepared by dissolving into the reactive monomers including water, made this class of monomers unique 1% of 1-hydroxy-cyclohexyl-phenyl-ketone. A drop among all acrylic and vinyl monomers. Consequently, of the composition was spread between glass/glass the anionic polymerization is initiated by traces of or glass/steel surfaces and subjected to UV radiation moisture which are to be found on almost all sur- with an intensity of 7 mW cm2 at 365 nm and faces. Accordingly, cyanoacrylate adhesives set very 4mWcm2 at 310 nm for 2 min. quickly when introduced between two surfaces stored under ambient conditions. Of the alkyl cyanoacrylate family of monomers, 13.4 Properties the methyl and ethyl esters are used extensively The particular advantage of cyanoacrylate adhesives in industrial and consumer-type adhesives. Conse- in terms of adhesives technology lies precisely in the quently, most of the published work on the poly- high reactivity coupled with the high bond strengths merization of cyanoacrylates focuses on anionic of the final materials, especially to polar substrates. polymerization. Due to high molar mass, good wetting properties, and polarity, poly(cyanoacrylate)s exhibit excellent adhesive properties. In addition, they have been found use- 13.3.1 Photo Curing ful as polymeric binding agents in controlled drug Although the predominant mechanism by which delivery systems. They are also useful for dry etching cyanoacrylate monomers undergo polymerization is processes. anionic, free-radical polymerization is also known to occur. Radical polymerization of cyanoacrylate can be achieved in the presence of a radical-forming com- 13.5 Applications and Uses ponent and a photosensitizer. The radical-generating Of the alkyl cyanoacrylate family of monomers, the component can be dibenzoyl peroxide and the methyl and ethyl esters are used extensively in indus- photoinitiator component is 2,4,6-triphenylpyrylium trial and consumer-type adhesives. tetrafluoroborate [47]. The chemical structures of these compounds are shown in Figure 13.11.Some metallocene salts are capable of generating both a 13.5.1 Rapid Prototyping cationic species and a free radical species upon expo- A three-dimensional printing process uses a pow- sure to radiation. der material as a substrate and a liquid binder as the ink. The three-dimensional printed specimens as such exhibit a porous structure and low mechanical strength. Therefore, three-dimensional prints are usually finished by an infiltration agent prior to their final use. For this, an epoxy resin, a cyanoacrylate, and a poly(urethane) are commonly used [50]. The type of C OOC infiltration agent greatly influences the final properties O O of the prints. O It has been reported that as a result of such post- treatment, the mechanical strength can be increased - BF4 by 100%. However, this is strongly influenced by the Figure 13.11 Dibenzoyl peroxide and 2,4,6-triphenyl- infiltration depth, which depends on the porous struc- pyrylium tetrafluoroborate. ture as such and the viscosity of the resin [51]. Propery of Reed Elsevier

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Table 13.8 Resist Composition [49]

Compound Amount (%) Cyclohexanone 88.5 Copolymer 11 Di-tert-butylphenyliodonium perﬂuorooctanesulfonate 0.44 Perﬂuorobutylsulfonyloxybicyclo[2.2.1]-hept-5-ene-2,3-dicarboximide 0.11 Tetrabutylammonium hydroxide 0.011

13.5.2 High-resolution hexafluoroarsenates, triflates, perfluoroalkane sul- Lithography fonates, substituted aryl sulfonates, and many others. A typical resist composition is shown in Table 13.8. In the microelectronics industry involving the con- struction of micromachines or magnetoresistive heads, there is a continued need to reduce the size of 13.5.3 Cosmetic and Medical structural features [49]. The ability to obtain a finer Applications resolution is limited by the wavelength of the light Cyanoacrylates are also used as adhesives in the ordi- used to create the lithographic pattern. The trend nary household. A case of an accidental aspiration of has been to move from so-called I-line radiation at a cyanoacrylate adhesive has been reported [52]. The 350–248 nm radiation with the goal to further reduce use of cyanoacrylate compounds in medical applica- the wavelength. tions has been reviewed [53]. A resist composition must possess desirable opti- Poly(alkyl cyanoacrylate)s are biodegradable and cal characteristics to enable image resolution at the biocompatible polymers. Ethyl cyanoacrylate, butyl desired radiation wavelength. The resist composition cyanoacrylate, and octyl cyanoacrylate have been must also possess suitable chemical and mechanical approved by the US Food and Drug Administration properties to enable the transfer to the image from the (FDA) [54]. Such polymers have also been proposed patterned resist to a substrate layer. as raw materials for the synthesis of nanoparticles to Resist compositions have been described, which are be used for drug delivery. capable of high resolution with [49]:

• improved stability/shelf-life, 13.5.3.1 Manicure Composition • improved etch resistance, Cyanoacrylate compositions are used as manicure compositions in treating chapped nails. When nails are • improved wettability, and manicured, it is generally observed that the moisture • improved thin-film adhesion. content in the nails becomes out of balance or lipids are eluted out from the nails. As a result, nail chapping The resists are imageable using 193 nm imag- proceeds under the manicure coating. Therefore, the ing radiation. The resist composition comprises an nail chapping can be prevented by adding to manicure imaging polymer, i.e., a 2-cyanoacrylate monomer, compositions a substance capable of keeping nails in and a radiation-sensitive acid generator. In detail, good health or improving the nail health. the polymer is a copolymer of methylcyclopentyl- Cyanoacrylates are hardened so quickly that the 5-norbornene-2-carboxylate and ethyl cyanoacrylate hardening reaction thereof is associated with heat gen- [49]. The polymerization is carried out with 2,2- eration. Therefore, when cyanoacrylates are applied azobisisobutyronitrile as radical initiator at 75 ◦C. to nails, there arises heat irritation. Avocado oil and To this copolymer an organic solvent is added, a jojoba oil can be added as plasticizer. In addition, these hydrophobic additive, which must be substantially oils can suppress the heat generation upon hardening transparent at 193 nm radiation. Bis-adamantyl tert- without deteriorating the quick hardening properties butyl carboxylate is preferred for such a purpose. of cyanoacrylates or impairing its storage stability. Acid generators include triaryl sulfonium hexafluo- Furthermore, these natural oils may prevent nails from roantimonate, diaryliodonium hexafluoroantimonate, keratinization [55]. Propery of Reed Elsevier

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13.5.3.2 Leak Control There has been a great deal of interest in using tissue adhesives in many surgical procedures in place Embolization of Blood Vessel Ruptures. A of sutures and staples for a variety of reasons, traumatic rupture of the abdominal aorta commonly including [61]: results in a rapid exsanguination and death before the patient reaches the hospital. In certain cases an 1. ease of application and reduced clinician time, open surgical repair can be performed. However, there are other methods, such as a repair using stent 2. location of repairable site as in contoured grafts. An embolization can be done using N-butyl- locations, 2-cyanoacrylate with or without associated metallic 3. biomechanical properties as in weak organs, such coils [56]. as liver and pancreas, and 4. minimized hypertrophy and scar formation as in Air Leaks after Lung Resection. 2-Octyl plastic surgery. cyanoacrylate was used as an adjunct to control air leaks after lung resection by application directly onto However, there have been a number of concerns ass- the visceral pleura [57]. The indications of this treat- ociated with the alkyl cyanoacrylates. These include: ment included a lack of standard sealants in patients with emphysematous lung that would not hold suture 1. their low viscosity and associated difﬁculties in and vast air leaks after decortications or extensive non- precise delivery at the application site in non- anatomic resections in patients that would not toler- medical and medical applications, ate the loss of tidal volume. All the air leaks sealed 2. poor shear strength of the adhesive joint, partic- immediately. There were no complications nor toxic- ularly in aqueous environments in both medical ity directly related to the 2-octyl cyanoacrylate resin. and non-medical applications, 2-Octyl cyanoacrylate is extremely effective in immediately controlling air leaks. It dries quickly, does not 3. high modulus or stiffness of cured polymers wash off the lung, and remains intact on the visceral at soft tissue application sites and associated pleura for several weeks. mechanical incompatibility, which can lead to adhesive joint failure and irritation of the sur- rounding tissue, 13.5.3.3 Skin Stripping 4. excessive heat generation upon application of Cyanacrylates can be used for skin surface biopsy monomers to living tissue due to the exception- because the polymers are formed with moisture and ally fast rate of curing resulting in necrosis, and adhere to the skin [58]. The stratum corneum is responsible for maintaining 5. site infection, among other pathological compli- a skin barrier function. In a medical study, samples cations, associated with prolonged residence of of the stratum corneum were collected for in vitro the non-absorbable tissue adhesives. investigations [59,60]. One drop of a cyanoacrylate resin was placed on a Problems with sterilization may arise. For example, glass slide. Afterwards the glass slide was attached to poly(2-octyl cyanoacrylate) degrades when exposed the test site with slight pressure and after a short time to a 160 ◦C dry heat sterilization cycle or 20–30 kGy of 1 min removed. (2–3 MRad) of electron beam radiation [13].

13.5.3.4 Tissue Adhesives 13.5.3.5 Bioabsorbable Polymers The isobutyl, n-butyl, and n-octyl cyanoacrylate esters Bioabsorbable polymers have been classiﬁed into are used clinically as blocking agents, sealants, and three groups [61,62]: tissue adhesives due to their much lower toxicity as compared with their more reactive methyl and ethyl • soluble, counterparts. Cyanoacrylate ester compositions can • be sterilized using visible light irradiation at room solubilizable, and temperature [12]. • depolymerizable. Propery of Reed Elsevier

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The most common materials used in bioabsorbable is mixed with ethyl cyanoacrylate in the presence of implants in orthopedic surgery [63] are poly(glycolic pyrophosphoric acid under a dry nitrogen atmosphere. acid), poly(lactic acid), and polydioxanone. The reaction is allowed to proceed by heating for 5 h ◦ Soluble polymers are water-soluble and have at 85 C[61]. hydrogen-bonding polar groups, the solubility being determined by the type and frequency of the polar References groups. Solubilizable polymers are usually insoluble salts, such as calcium or magnesium salts of car- [1] H.V. Coover, D.W. Dreifus, J.T.O. Conner, boxylic or sulfonic acid functional materials, which Cyanoacrylate adhesives, in: I. Skeist (Ed.), can dissolve by cation exchange with monovalent Handbook of Adhesives, third ed., Van Nos- metal salts. Depolymerizable systems have chains that trand Reinhold, New York, 1990 (Chapter 27), dissociate to simple organic compounds in vivo under pp. 463–477. the influence of enzymes or chemical catalysis. [2] Y.-P. Lv, X.-Y. Wang, B.-A. Song, S. Yang, K. Yan, G.-F. Xu, P.S. Bhadury, F. Liu, Ester of Triethylene Glycol. Bioabsorbable tis- L.-H. Jin, D.-Y. Hu, Synthesis, antiviral sue adhesives [62,64] are based on a methoxypropyl and antifungal bioactivity of 2-cyano-acrylate cyanoacrylate as the precursor of an absorbable tissue derivatives containing phosphonyl moieties, adhesive polymer and a polymeric, highly absorbable, Molecules 12 (5) (2007) 965–978. liquid comprising an oxalate ester of triethylene gly- [3] Q. Zhao, S. Liu, Y. Li, Q. Wang, Design, col as a modifier to modulate the viscosity of the synthesis, and biological activities of novel 2- overall composition, lower the heat of polymeriza- cyanoacrylates containing oxazole, oxadiazole, tion, and increase the compliance and absorption rate or quinoline moieties, J. Agric. Food Chem. 57 of the cured adhesive joint. Copolymers of caprolac- (7) (2009) 2849–2855. tone, D,L-lactide, and glycolide are also considered [4] T. Wang, W. Miao, S. Wu, G. Bing, X. Zhang, as bioabsorbable [61,65]. Z. Qin, H. Yu, X. Qin, J. Fang, Synthesis, crystal structure, and herbicidal activities of Cyanoacrylate-capped Heterochain Poly- 2-cyanoacrylates containing 1,3,4-thiadiazole mers. Although the admixture of a polymeric modi- moieties, Chinese J. Chem. 29 (5) (2011) fier has been shown to be effective in address- 959–967. ing most of the medical and non-medical [5] K.F. von Auwers, J.F. Thorpe, Studien in der drawbacks of cyanoacrylate-based adhesives rep- bernsteinsure- und glutarsure-gruppe. Ueber resented by methoxypropyl cyanoacrylate, there symmetrische α,α-dimethylglutarsuren, Liebigs remain technical drawbacks in these systems, such Ann. Chem. 310 (1895) 339. as mutual immiscibility of two or more polymers. [6] A.E. Ardis, US Patent 2 467 927, Assigned to Cyanoacrylate-capped heterochain polymers hav- B.F. Goodrich, New York (NY), April 19, 1949. ing two or more cyanoacrylate ester groups per chain [7] F.B. Joyner, G.F. Hawkins, Method of making α- have certain advantages. The heterochain polymer cyano-acrylates, US Patent 2 721 858, Assigned used for capping can be one or more absorbable to Eastman Kodak, Rochester, New York, polymers of the following types: polyester, polyester- October 25, 1955. carbonate, polyether-carbonate, and polyether-ester. [8] A.E. Ardis, Preparation of monomeric alkyl-α- The capped polymer can also be derived from a cyano-acrylates, US Patent 2 467 926, Assigned polyalkylene glycol such as PEG, or a block copoly- to B.F. Goodrich, New York (NY), April 19, mer of PEG and poly(propylene) glycol. 1949. The capping of the heterochain polymer can [9] A. Vojtkov, K.A. Mager, Y.V. Kokhanov, A.M. be achieved using an alkyl cyanoacrylate, or an Polyakova, Y.B. Vojtekunas, Method of prepar- alkoxyalkyl cyanoacrylate such as ethyl cyanoacryl- ing cyanacrylic acid esters, US Patent 726 086, ate or methoxypropyl cyanoacrylate, respectively, in Assigned to Inst. Elementoorganicheskikh So. the presence of phosphorus-based acids or precursors. (SU), April 5, 1980. In fact, the capping takes place as a transesterifica- [10] C.J. Buck, Modified cyanoacrylate monomers tion reaction. In the simplest case, a predried PEG and methods for preparation, US Patent 4 012