Polymers Knoevenagel reaction

Literature articles, which report the formation and evaluation of difunctional cyanoacrylate monomers, have been published. The preparation of the difunctional monomers required an alternative synthetic method than the standard Knoevenagel reaction for the monofunctional monomers, because the crosslinked polymer thermally decomposes before it can revert back to the free monomer. The earliest report for the preparation of a difunctional cyanoacrylate monomer involved a reverse Diels-Alder reaction of a dicyanoacrylate precursor [16,17]. Later reports described a transesterification with a dicyanoacrylic acid [18] or their formation from the oxidation of a diphenylselenide precursor, seen in Eq. 3 for the dicyanoacrylate ester of butanediol, 7 [6]. 

Introduction of these photocrosslinkable structures in macro-molecular chains can be performed by esterification of hydroxyla-ted polymers with cinnamoyl chloride. Cellulose Q).condensation products (4, ) and mainly poly(vinyl alcohol) have Been treated( by this method. Other chemical modifications have been studied as ester interchange of poly(vinyl acetate) 7) and Knoevenagel reaction on polyesters (8). Very few results on the synthesis of such photocrosslinkable polymers by polymerization have been reported. Therefore free radical polymerization of cinnamic acid vinyl derivatives did not lead to the expected polymers, but to insolubilization reactions. Howewer cationic procedure can be a good way in some cases since Kato et al. could polymerize by this way with high yields p-vinyl phenylcinnamate (9) and B-vinyloxyethyl cinnamate (10). 

Several strategies for the synthesis of polymer-bound enones have been described. One way is to start from immobilized [f-ketoesters, which can be prepared via transesterfica-tion of Wang resin with alkyl fl-keto carboxylates [31], or by treatment with diketene [16]. Knoevenagel reactions of these polymer-bound [f-ketoesters with aldehydes led to the formation of 2-alkylidene- or arylidene-P-ketoesters (Fig. 6.19 (A)). 

Hollinshead [32] used polymer-bound enones for the synthesis of highly functionalized pyrrolidines. 3-Hydroxyacetophenone was immobilized on chlorinated Wang resin and transformed into polymer-bound enones upon a Knoevenagel reaction with aldehydes. Pyrrolidines were then formed in the addition of azomethinylides, generated from imines, LiBr and DBU (Fig. 6.24). 

Having elucidated the optimum conditions for the Knoevenagel reaction in a flow reactor, a range of other reactions using different activated methylene derivatives and aldehydes (Table 14.3) was conducted. In all cases excellent product purities and yields were obtained. The reaction of benzaldehyde and ethyl cyanoacetate was also performed using 3-(dimethylamino)propyl-functionalized silica gel, 3-aminopropyl-functionalised silica gel, 3-(l,3,4,6,7,8-hexahydro-2H-pyrimidojl, 2-l]pyrimidino)propyl-functionalized silica gel and polymer-supported diazabicyclo[2.2.2]octane, whereby excellent conversions were obtained (> 99.0%) in all cases [37]. 

The Knoevenagel reaction [3] is one of the most important C-C bond-forming reactions available to synthetic chemists. It is widely used in the synthesis of important intermediates or end-products for perfumes [4], pharmaceuticals [5], e. g. antihypertensive and calcium antagonists [6], and polymers [7]. The reaction is catalyzed by bases, acids, or catalysts containing acid-base sites [8], e. g. bases such as ammonia, primary and secondary amines and their salts [1], and Lewis acids such as CUCI2 [9], ZnCl2 [10], and Sml3 [11]. 

The cyanoacryhc esters are prepared via the Knoevenagel condensation reaction (5), in which the corresponding alkyl cyanoacetate reacts with formaldehyde in the presence of a basic catalyst to form a low molecular weight polymer. The polymer slurry is acidified and the water is removed. Subsequendy, the polymer is cracked and redistilled at a high temperature onto a suitable stabilizer combination to prevent premature repolymerization. Strong protonic or Lewis acids are normally used in combination with small amounts of a free-radical stabilizer. 

As discussed in Section 7.1.4, polymer-bound acetoacetates can be used as precursors for the solid-phase synthesis of enones [33], For these Knoevenagel condensations, the crucial step is to initiate enolization of the CH acidic component. In general, enolization can be initiated with a variety of catalysts (for example, piperidine, piperidinium acetate, ethylenediamine diacetate), but for the microwave-assisted procedure piperidinium acetate was found to be the catalyst of choice, provided that the temperature was kept below 130 °C. At higher reaction temperatures, there is significant cleavage of material from the resin. 

Poly(chalcones) (183), which themselves are the products of Knoevenagel condensation of aromatic dialdehydes and diacetyl compounds, have been transformed into polylpyrazo-lines) (185) by reaction with phenylhydrazine (184) (72MI11107). The reaction (Scheme 88) was conveniently conducted in excess phenylhydrazine and yielded polymers which were described as being brilliantly fluorescent in solution. The poly(pyrazolines) (185) exhibited glass transition temperatures between 150 and 210 °C and were stable, in some cases, up to 630 °C. 

Solid-phase synthesis is of importance in combinatorial chemistry. As already mentioned RuH2(PPh3)4 catalyst can be used as an alternative to the conventional Lewis acid or base catalyst. When one uses polymer-supported cyanoacetate 37, which can be readily obtained from the commercially available polystyrene Wang resin and cyanoacetic acid, the ruthenium-catalyzed Knoevenagel and Michael reactions can be performed successively [27]. The effectiveness of this reaction is demonstrated by the sequential four-component reaction on solid phase as shown in Scheme 11 [27]. The ruthenium-catalyzed condensation of 37 with propanal and subsequent addition of diethyl malonate and methyl vinyl ketone in TH F at 50 °C gave the adduct 40 diastereoselectively in 40 % yield (de= 90 10). 

Thereby it must be emphasized that the application of methods from organic chemistry in polymer synthesis was only possible for chain structures, that are sufficiently soluble (see section 1.3). Here again, careful consideration of the mechanistic details of the reaction and the occurrence of side reactions are important ingredients of both oligomer and polymer synthesis. Thus, the Knoevenagel eondensation is feasible for eyano-substituted precursors 71... 

---