Imidazole 4-vinylimidazole

So far, many kinds of nucleophiles active for hydrolysis such as imidazolyl-, amino-, pyridino-, carboxyl- and thiol-groups, have been used for preparation of hydrolase models. Overberger et al.108,1091 prepared copolymers of vinylimidazole and acrylic acid 60 (PVIm AA), by which the cationic substrate, 61 (ANTI), was hydrolyzed. This kind of copolymer is considered to be a model of acetylcholinesterase. With ANTI, the rate of the copolymer catalysis was higher than that of imidazole itself in the higher values of pH, as is seen in Table 9. In this work, important contributions of the electrostatic interactions are clear. The activity of the copolymer was not as high with the negatively charged and neutral substrates. 

Shimidzu etal.111 studied the catalytic activity of poly (4(5)-vinylimidazole-co-acrylic add) 60 (PVIm AA) in hydrolyses of 3-acetoxy-N-trimethylanilinium iodide 61 (ANTI) and p-nitrophenylacetate 44 (PNPA). The hydrolyses of ANTI followed the Michaelis-Menten-type kinetics, and that of PNPA followed the second-order kinetics. Substrate-binding with the copolymer was strongest at an imidazole content of 30 mol%. The authors concluded that the carboxylic acid moiety not... 

Similarly, /V-sulfonyl-protected vinylimidazole 597 reacts with PTAD to provide the cycloaddition reaction product 598 which easily undergoes the retro-Diels-Alder reaction upon heating or with acid treatment. The primary product is easily isomerized using a base to the aromatized condensed imidazole 599 (Scheme 95) <1998TL4561>. 

First-Order Observed Rate Constants for 1 1.95 Imidazole-Phenol Copolymer, Poly-4(5)-vinylimidazole, and Imidazole-Catalyzed Solvolyses of PNPA° ... 

Copolymer of 4(5)-vinylimidazole and p-vinylphenol Poly-4(5)-vinylimidazole Imidazole... 

As one might expect the rate of p-nitrophenyl heptanoate hydrolysis increased at low ethanol concentrations as a result of apolar binding. The rate of p-nitrophenyl acetate hydrolysis also increased markedly at low ethanol concentration. This finding was explained by a conformational effect on the polymer, that is, lower ethanol concentration brings about a shrinkage of the polymer, which increases concerted interactions of the imidazole residues. The hydrolysis of 3-nitro-4-dodecanoyloxybenzoate was found to be 1700 times faster in the presence of poly[4(5)-vinylimidazole] compared to free imidazole (77). A double-displacement mechanism was demonstrated for this system (75). 

Certain transition metal complexes can serve as templates for the synthesis of chelating NHC ligands. For example, 1-phenylphosphole complexes of pal-ladium(II) are attacked in a Diels-Alder reaction by 1-vinylimidazole. If 1,2-dichloroethane is used as the solvent the imidazole is alkylated in situ and then subjected to a spontaneous carbometallation reaction [Eq. (37)]. 

Overberger and coworkers carried out an interesting study on the hydrolysis of various 3-nitro-4-acyloxybenzoic acid substrates (V) catalyzed by imidazole (VI) and poly[4(5)-vinylimidazole] (VII) in ethanol-water mixtures [Overberger et al., 1973]. 

Chain transfer to the monomer is discussed by Van den Grampel in connection with polymerization of N-vinylimidazole in the presence of poly(methacrylic acid). Degradative addition by a radical at the 2-position of the imidazole ring can be illustrated by the reaction ... 

Additions to /V-alkeny I imidazoles are influenced by conjugation with the heteroring (Equation 9) a vinyl group is not cleaved when l-vinyl-3-alkyl quaternary salts are thermolyzed and 1-vinylimidazole is not subject to thermal rearrangement (80AHC(27)24t, 82CHEH90,84JHC133). 

Imidazole-containing polymers and copolymers have been obtained from a variety of derivatized imidazoles, including the unsubstituted 1-, 2- and 4(5)-vinylimidazole monomers. Primary interest in these polymers has centered around metal complexation, ion exchange and catalytic properties. 

In the area of catalysis, the esterolysis reactions of imidazole-containing polymers have been investigated in detail as possible models for histidine-containing hydrolytic enzymes such as a-chymotrypsin (77MI11104). Accelerations are observed in the rate of hydrolysis of esters such as 4-nitrophenyl acetate catalyzed by poly(4(5)-vinylimidazole) when compared with that found in the presence of imidazole itself. These results have been explained in terms of a cooperative or bifunctional interaction between neighboring imidazole functions (Scheme 19), although hydrophobic and electrostatic interactions may also contribute to the rate enhancements. Recently these interpretations, particularly that depicted in Scheme 19, have been seriously questioned (see Section 1.11.4.2.2). 

Fig. 18 Reaction rate of hydrolysis of p-nitrophenyl acetate as a function of inverse temperature. Thermosensitive imidazole-containing copolymers (PVCL-Vim, PNIPA-Vim), 1-methylimidazole and poly(l-vinylimidazole) act as catalysts. Numbers in the copolymer abbreviations denote the Vim content (in mole percent). Vim 1-vinylimidazole. (Adapted from Ref. [18])...

Both poly(l-butyl-5-vinylimidazole), poly(lB-5IM), and poly(l-methyl-5-vinyl-imidazole), poly(lM-5IM), have no quatemizable nitrogen, so that the coulombic interaction with the substrate is not necessarily to be considered. Using these polymers, hydrolyses of several 3-nitro-4-acyloxy benzoic acid having various acyl chain length (8) (n = 0,5,10,16) have been made (55). The apparent rates of hydrolyses are tabulated in Table 7. 

Accordingly, several kinds of combinations such as IM+-IM+, IM+-IM, IM-IM, IM-IM-, IM- -IM-, can be thought to be in poly(4(5)-vinylimidazole). The cooperation of imidazole in the catalysis can be seen in the hydrolysis of sym-dichloro-acetone by imidazole in 95% dioxane solution (71). The rate of the hydrolysis is represented as... 

The degree of polymerization of poly(4(5)-vinylimidazole) greatly affects the catalysis rate, kat, and the fraction of the neutral imidazole moiety in the polymer (73,90). In hydrolyses of the negatively charged substrate, NABS (1), and the neutral substrate, PNPA(5), the k increases with the degree of polymerization. 

Fig. 4. Rates of hydrolysis of PNPA by poly(4(5)-vinylimidazole) and imidazole...

The reduced activity of poly(4(5)-vinylimidazole) in comparison to imidazole in the hydrolyses at low t i values, as is shown in Fig. 4, is considered (70) A larger fraction of the protonated imidazole moieties excludes the substrate or a more extended conformation of the polymer which is caused by an increase of the protonated imidazole moieties and renders difficult the IM-IM cooperation. 

IM-IM cooperation. It is difficult to establish the IM-IM" cooperation in poly(4(5)-vinylimidazole), since pK2 value is more than 14.5 (74). The IM-IM" cooperation can be observed in hydrolyses of PNPA(5) and 4-acetoxy-3-nitrobenzoic acid [n = 0 in (8)] by poly(5(6)-vinylbenzimidazole), of which pK2 value is estimated to be 12.7 (26). The hydrolyses rates increase sharply as the pH approaches the pK2 value of the polymer. In contrast, such a drastic enhancement in the rate is not observed in the benzimidazole-catalysed hydrolysis, nevertheless, pK2 value of the benzimidazole being 12.7. N-Alkylated polymers such as poly(N-vinylimidazole), poly(NIM), and poly(2-methyl-N-vinylimidazole), poly(2MIM), which have no anionic form in imidazole moieties, show the hydrolytic activities slightly less than that of poly(4(5)-vinylimidazole). In cases of low molecular weight analogues, such as N-methylimidazole and imidazole, the hydrolytic activity of the former is about 75% of the activity of imidazole (75, 76). These phenomena appear to support the IM-IM" cooperation in poly(4(5)-vmylimidazole) indirectly. In the hydrolyses of NABS(l) and NABA(3) by poly(5(6)-vinylbenzimidazole), the activity enhancement is about 50-fold compared with the activity of benzimidazole, in spite of these anionic substrates being used (23, 26). 

IM-OH cooperation. It is interesting that the appearance of a cooperation between imidazole and hydroxyl moieties in the synthetic polymer is found, as is observed in a-chymotrypsin-catalyzed hydrolysis. The cooperation is ascertained in the hydrolyses catalyzed by copolymers of 4 5)-vinylimidazole with vinyl alcohol, poly(IM-al) (VI), and with p-vinylphenol, poly(IM-ph) (VII) (77, 78). 

Molar extinction coefficients of both protonated and neutral imidazole moietis increase with the content of carboxyl groups in the poly(4(5)-vinylimidazole-co-... 

IM-COOH-OH cooperation. Polymers such as poly(4(5)-vinylimidazole-co-7-vinyl-7-butyrolactone), poly(IM-la), and poly(4(5)-vinylimidazole-co-acrylic acid-covinyl alcohol) derived from poly(4(5)-vinylimidazole-co-methyl acrylate-co-vinyl acetate), both of which contain imidazole, carboxylic acid and hydroxyl moieties are synthesized and studied as a model of a-chymotrypsin (29). The former has a relatively ordered sequence and the latter has a random one. Results are tabulated in Table 11. The polymers cited in the Tabel contain a similarly low quantity of imidazole moiety, so that the cooperation of two subsequent imidazole moieties need not be discussed. Polymers such as L-84, L-68, M-83 and A-84 have higher catalytic activities than the polymer V-82. This suggests that the catalytic activity of the imidazole moiety in the polymers is much promoted by the carboxylate moiety in the polymers. The catalytic activities of L-84 and L-68 which have an ordered sequence are more than twice as high as that of M-83, having a random sequence. From these results it is concluded that the introduction of the hydroxyl moiety which has little cooperative effect on the imidazole moiety in V-82 in this reaction conrfition into imidazole and carboxylate — containing polymer, increases... 

A clear-cut molecular relay system is materialized with the combination of two nucleophile moieties such as hydroxamic acid and imidazole introduced in a polymer (38, 40, 82). Hydroxamate anion has a high nucleophilicity but deacylation of the acylhydroxamate is very slow. The significance of the deacylation step in the hydrolysis in polymer catalyst is pointed out in several works, for example, the deacylation of acetylated poly(4(5)-vinylimidazole) (83,84) and the aminolysis of nitrophenyl ester of poly(styrene-co-acrylic acid) (85—87). To promote the deacylation velosity of the acylated hydroxamic acid imidazole moiety is introduced in the hydroxamic acid-containing polymer. The polymers are shown in tire following page. 

The significance of the coulombic field is observed (79). Figure 9 shows the catalytic activities of poly(4(5)-vinylimidazole-co-acrylic acid), poly(IM-ac), and low molecular weight imidazole derivatives in hydrolyses of various substituted phenyl acetates of which leaving groups have different activities. 

Alkenyl groups in A-alkenylazoles act as weak or moderate -electron acceptors. Thus, the basic pKa of 1-vinylimi-dazole (5.14) is nearly 2 pK units lower than that of imidazole. Examination of 1SN NMR spectra of 1-vinylimidazoles and -benzimidazoles shows that the nitrogen attached to the vinyl group resonates in at a higher field than N(3). In accord with these results 1-vinylimidazoles form less stable complexes with transition metals than 1-alkylimidazoles. 

Proton conducting copolymers of vinylphosphonic acid and 4-vinylimidazole have been reported recently by Bozkurt et al. [7]. Since the imidazole ring can act as a proton hopping site in the polymer matrix [8-10], these copolymers had ionic conductivity of about 10 S cm at 60°C without solvent or salt. To realize fast proton transport in copolymer systems, it is essential to design an ion conductive paths that uses the IL domain. 

---