CHAPTER I11 MOLECULAR REARRANGEMENT IN MACROMOLECULAR CAVITIES

CHAPTER I11 MOLECULAR REARRANGEMENT IN MACROMOLECULAR CAVITIES The concept of 'cavity in solution' has been put forward by Cramer in 1950's during his revolutionary work on inclusion compounds 157f158. He believed that molecules of suitabe size and geometry can be trapped in these organized cavities without any chemical bonding. Structure of the inclusion compounds in the near vicinity of the entrapped molecules is exemplified by the structure of the solvents in the environment of an ion. ~hysicochemists were against to this hypothesis. A start in research of inclusion compounds was made around 1960s and in the following years many papers were published related to the synthesis and molecular transformation of diverse compounds which have excellent applications in the field of agriculture, pharmaceuticals and industry 159-166 The establishment of a correlation between the molecular movement of the organic substrates within organized macromolecular assemblies and the rate and extent of molecular rearrangement form the subject matter for this chapter. Polyethyleneglycols (PEGS) were used for mimicking the typical inclusion compounds like cyclodextrins and crown polyethers in these investigations 167-170. Benzil-benzilic acid rearrangement

was carried out in PEG media of different concentrations and molecular weights. The encapsulation of & -diketone systems in the cavities of styrene based copolymers and its rearrangement to a-hydroxy acids were also studied. A system containing a rearrangeable molecular species was encapsulated in these cavities. These systems are completely immobilized in contrast to the conventional inclusion compounds. The behaviour of encapsulated molecules in the ordered cavities of inclusion compounds and the immobilized low-molecular weight species appended on insoluble crosslinked polymeric network can be compared here. Moreover, the systems can be suggested as alternatives to chemically functionalized polymers. The introduction of a low-molecular weight functional species into the polymeric backbone is carried out through a series of polymer-analogous reactions which is a laborious, time-consuming process. The loading of the required functional group might be seriously affected by this prolonged treatment eventhough the initial capacity of the resin is high. The problems can be overcome if the required low molecular weight species can be introduced directly into the polymer matrix during the process of polymerization as a guest molecule. The encapsulation of low molecular weight organic molecules in the cavities of the three

dimensional polymeric networks without any chemical bonding could lead to the low molecular weight properties for these molecules 1711172. At the same time, the resulting polymer will have physical properties typical of a functionalized polymer. Here the encapsulation of &-diketone in the cavities of styrene based copolymers and its rearrangement was icvestigated. These results can be compared with those of analogous reactions in a covalently supported polymer network and those in solutions. Instead of the stepwise sequential synthesis of the benzil analogues, the benzil encapsulated polymer was prepared in a single step. The polymer-incorporated K-diketone was subjected to rearrangement. A comparison between the molecular encapsulation and the preparation of colvalently bonded &-diketone is given in Scheme 111.1. Crosslinked polymers consist of infinite networks in which linear chains are interconnected by the bifunctional monomer. In the case of styrene based copolymers, inner spaces or cavities of definite size are produced during polymerization process depending on the nature of the crosslinking agent. For DVB-crosslinked polystyrenes, these cavities have a hydrophobic environment. Molecules can be trapped in these 'pockets' without recourse to

Scheme 111.1. Preparation of covalently bound polymeric benzil and encapsulated benzil A: Monomer, B: Crosslinking monomer chemical bonding. The method can be used for the functionalization of polymers if the size and geometry of the guest molecules are acceptable to the geometry of the cavities (Scheme 111.2).

A + B F Encapsulation @- F Scheme 111.2- Two routes for the pregaration of functional polymers A, B: Monomers; F', Fn& F"': Reagents F,F1, & F2: Functional groups Butanediol dimethacrylate (BDDMA) and ethyleneglycol dimethacrylate (EGDMA) are also used as the crosslinking agents in the process of encapsulation. The resulting polymers were subjected to benzil-benzilic acid rearrangement under basic conditions.

RESULTS AND DISCUSSION Benzil-Benzilic Acid Rearrangement in Soluble Macrornolecular Cavities As part of the studies of molecular rearrangements in macromolecular matrices, the relation between the molecular movement and the rate and extent of the rearrangement was ineestigated. For this purpose, the course of benzil-benzilic acid rearrangement was followed in macromolecular assemblies. The commonly available and cheap PEG derivatives were used for these studies. PEG with different molecular weights (which could lead to different cavity sizes) were employed for the investigations. Polymeric media with different PEG concentrations were prepared in a water-alcohol mixture and the viscosity of the medium was measured using an AVS- 400 viscometer. Rearrangement was carried out in these organized media using low molecular weight benzil. The reactions were conducted under identical conditions and the kinetics of the reaction was followed titrimetrically. Rate constants were calculated following the second order rate equation for benzil-benzilic acid rearrangement. It was expected that, as the PEG concentration increases, the rate of rearrangement will normally decrease. This is due to the reduced molecular movement

of the reagent molecules into the interior cavities of the macromolecular assemblies. Such a situation will create the partial inaccessibility of the rearranging systems to the attacking species. As the concentration of the medium increases, the molecular movement decreases and consequently the inaccessibility increases. This can be correlated to the increased degree of crosslinking in heterogeneous polymeric systems with rearrangeable functional groups. Thus, crosslinking can be considered as a case of infinite viscosity. To derive correlation between the viscosity of the soluble macromolecular assemblies and the crosslink densities of insoluble polymeric matrices, a series of kinetic investigations were carried out. (a). Benzil-Benzilic Acid Rearrangement in PEG-400 and PEG-6000 Media Polyethyleneglycol with molecular weight 400 was selected for the preliminary investigations. 5, 10, 15 and 20% solutions of PEG-400 in water-ethanol mixture were prepared. Low molecular weight benzil and potassium hydroxide were added to the mixture and the progress of the reaction was followed titrimetrically. Rate constants were calculated according to the second order rate equation of benzil-benzilic acid rearrangement. The average rate constants were calculated. These results are presented in Table 111.1.

Table 111.1. Benzil-benzilic acid rearrangement in. PEG-400 medium PEG concen- Avarage time Viscosity of Mean k -1 tration of flow (mole/litre) (8) ( sec (Kg m s min- From Table 111.1, it can be seen that, in contrast to the expectation, the rate of rearrangement increases with increased concentration of the PEG medium (Figure 111.1). For the control experiment constructed without adding any PEG, -1 min the rate constant was 1.79 x lom4 (mole/litre)-' It was observed that the rate pf the reaction is directly proportional to the PEG concentrtion and a regular increase in rate constant was observed with increase in the PEG content. For the reaction where 20% PEG medium was used, the rate constant was observed as 4.67-1 x (mole/litre)-i min.

Concentration of PEG (%) Figure 111.1. Concentration of PEG rate constant The cation binding property of the PEGS is responsible for this unexpected results 160,173-179. In the second series of experiments, PEG-6000 was used for

the kinetic investigations. PEG-6000 is freely soluble in water. A set of reaction media was prepared by varying the concentration of PEG. The rearrangement was carried out under identical conditions. Rate constants were calculated and the values are presented in Table 111.2. Table 111.2. Benzil-benzilic acid rearrangement in PEG-6000 medium PEG concen- Avarage time Viscosity of Mean k tration of flow (m~le/li~re)-~ - (%I (sec) (Kg m s min Here also, the relation between the rate constant and PEG concentration is linear (Figure 111.2). For the blank experiment the rate constant obtained was 1.78 x loa4 (mole/litre)-i min-l. A gradual increase in the k values was observed upto the 20% medium. Rate constant of the reaction in the 20% medium was 5.63 x min -1. (mole/litre)-'

0 5 10 15 20 2 5 concentration of PEG (8) Figure 111.2. Concentration of PEG & rate constant

(b). Model Reaction I: Hydrolysis of Ethyl Acetate in PEG-6000 Medium A simple model reaction was selected to extend the studies on the relation between molecular mobility and the rate of reactions. The kinetics of the hydrolysis of ethyl acetate was followed in PEG-6000 medium. A set of experiments was arranged by dissolving PEG at different concentrations in dilute HCl. The reactions were conducted in a thermostat at constant temperature. Measured quantity of ethyl acetate was added and the kinetics of the reaction was followed titrimetrically. The rate constants were calculated. The k values are given in Table 111.3. Table 111.3. Hydrolysis of ethyl acetate in PEG-6000 medium PEG concen- Viscosity of Mean k tration (mole/&*tre)-' (%) (Kg rn s min

From these results, it can be seen that the rate constant is inversely proportional to the concentration of PEG (Figure 111.3). For the control experiment the rate constant was recorded as 6.06 x (mole/litre)-lmin-i whereas the reaction in 20% PEG solution shows a k value -1 which is equivalent to 3.18 x (rnole/litre)-i min. The decreased mobility of the substrate molecules appears to be responsible for this phenomenon. 0 5 10 15 20 2 5 Concentration of PEG (%I Figure 111.3- Kinetics of the hydrolysis of ethyl acetate in PEG-6000 medium

(c). Model Reaction 11: Saponification of ester in PEG-6000 Medium The saponification of ethyl acetate which is a second order reaction was selected to investigate the cation binding property of the polyethyleneglycols under rearrangement conditions. PEG-6000 was used for this purpose. A series of solutions with different PEG contents were prepared and the saponification was carried out in these solutions. Kinetics was followed titrimetrically and the rate constants were calculated. The results are presented in Table 111.4. Table 111.4. Saponification of ethyl acetate in PEG-6000 medium PEG concen- Viscosity of Mean k tration (mole/i.$tre)-l (%) (Kg m s min Here also a linear relationship was observed between the rate constant of the reaction and concentration of the medium. For the control experiment the rate constant was

5.60 x (mole/litre)-i inin-'. For 20% PEG solution the observed k value is 11.56 x lo-' (mole/litre)-i min-l. Polyethyleneglycols are known to complex metal ions. This property brings the possibility of increased salt solubility and increased anion reactivity in organic solvents. PEG with molecular weight 400 and 6000 can complex with potassium ions and thus facilitate release of hydroxide ions from KOH. The selective cation binding property of the polyethyleneglycols thus increased the mobility and reactivity of the anions. Benzil-benzilic acid rearrangement is usually effected by employing potassium hydroxide as the reagent. In presence of PEG, potassium ions are selectively complexed and more reactive exposed anions are present in the solution. Due to the increased reactivity of the anions, the rate of the rearrangement increases. The cation binding property and hence the increased reactivity of the reagent takes predominance over the constraints imposed by the viscous medium on the mobility of the anions.. 2. Encapsulation of 1,2-Diketo Systems in the Cavities of Crosslinked Polymeric Networks and its Rearrangement to CX!-Hydroxy Acids The encapsulation of reactive organic substrates in the cavities of macronet polymers was investigated and suggested as an alternative route for the conventional

multi-step synthesis of functional polymers. Crosslinked polystyrene- @ -diketone system was studied as a model reaction. Crosslinking copolymerization of styrene with divinylbenzene in the presence of benzil in the dissolved state resulted in the formation of benzil encapsulated styrene-divinylbenzene crosslinked polymeric systems. Benzil encapsulated polymers were synthesised with varying crosslink densities by adjusting the styrene/dvb monomer ratio. The results are discussed in terms of the selective molecular size of the guest molecules and the cavity dimensions within the host polymeric systems. Experiments were carried out by changing the crosslinking agents. Butanediol dimethacrylate (BDDMA) and ethyleneglycol dimethacrylate (EGDMA) were employed as the crosslinking agents. The molecular character and cavity dimensions of the substrate encapsulated polymeric system were drastically changed with the changes in the crosslinking agents. The behaviour of these polymeric systems towards encapsulation process and the stability of the encapsulated systems are different for different polymer systems. The benzil-encapsulated polymers were characterized by spectral analysis and the stability of these resin were tested by treatment with different organic solvents, dilute acid and alkalies at various temperatures.

(a). Encapsulation of Benzil Molecules in the Cavities of DVB-Crosslinked Polystyrene Networks Crosslinking copolymerization of styrene with DVB in the presence of benzil in the dissolved state resulted in the formation of benzil entrapped styrene-dvb polymeric systems. Free radical initiated suspension polymerization technique was selected for the polymerization. The guest molecules were dissolved in the diluent and mixed with the monomer mixture and the initiator. It was then added to the PVA solution (MW. 72000 )and heated at 80 c for about 6 h with mechanical stirring. The precipitated polymer was washed with water, methanol, benzene and dichloromethane. The yellow coloured polymer obtained was characterized by IR spectra. A strong band corresponding to the C=O absorption apppeared at 1690 cm -1. A comparison between the IR spectra of PS-DVB copolymer and benzil-encapsulated PS-DVB copolymer is possible from Figure 111.4. Figures 111.5 and 111.6 show the scanning electron micrographs of styrene-divinylbenzene ('2%) copolymer and its benzil encapsulated counterpart respectively. The surface of the crosslinked copolymer is rough with a wrinkling effect. This shows the presence of empty space or 'cavities' within the system. The cavities disappeared during encapsulation (Figure 111.6). In contrast to the corrugated surface of the styrene-dvb copolymer, the encapsulated system shows a relatively smooth surface.

basis of the cavity sizes of the polymeric networks and molecular dimensions of the guest molecules. As the crosslink density changes, the cavity dimensions and sizes drastically change and it becomes unsuitable for the guest molecules. The foreign molecules with suitable molecular dimensions are entrapped in the well defined cavities of the polymer matrix. These cavities are designed by the three-dimensional arrangement of the structural units in the polymer systems. A typical situation is expressed in Scheme 111.3. If the cavity sizes are not suitable to accomodate the guest molecules, the molecules will not be accepted in the network and no encapsulation is possible. This may be the reason for the refusal of the 5 and 8% crosslinked resins to entrap the guest molecules. The morphology of the polymer like pore size and pore geometry are sensitively dependent on the polymerization conditions. With the variations in the temperature, rate of stirring and the distribution of the monomers in the suspension medium the polymer produced are of variable morphological characteristics. In actual practice, it is difficult to attain reproducibility in the case of higher crosslinked densities due to the faster polymerization kinetics. By trial, it is possible to determine the most suitable crosslinking for encapsulation.

Ibl Figure 111.5. Scanning electron micrographs of PS-DVB resin

Figure 111.6. Scanning electron micrograph of benzil-encapsulated PS-DVB resin DVR-crosslinked polystyrenes with different crosslink densities were prepared in the presence of the guest molecules. ~enzil was strongly entrapped in the networks of PS-DVB resins w ith 2, 3, 4 mole per cent crosslink densities, Benzil molecules entrapped in the cavities of resins with 5 and 8 mole per cent crosslink densities esca2ed on repeated washing. This can be explained on the

11 Scheme 111.3. Synthesis of benzil-encapsulated resin PS-DVB (b). Encapsulation of CC -Diketone in the Cavities of BDDMA-Crosslinked Polystyrene BDDMA-crosslinked polystyrene was prepared in presence of benzil in solution. Benzil was dissolved in the diluent and the polymerization was carried out by suspension polymerization in water. 2, 4, 6 and 8 mole

per cent crosslinked resins were prepared. It was observed that the guest molecules are entrapped in these polymers, though the extent of encapsulations are different. The yellow coloured resins were collected and the surface adsorbed benzil, if any, was removed by washing. The dried resin was characterized by IR spectroscopy. Typical IR spectra of PS-BDDMA resin and the corresponding benzil encapsulated resin are given in Figure 111.7. Benzil molecules are entrapped in the well-defined cavities of styrene-bddma copolymer. The surface properties of the polymer and the encapsulated system are different (Figures 111.8 and 111.9). The molecular representation of the benzil- encapsulated PS-BDDMA resin is given in Scheme 111.4. Scheme 111.4. Synthesis of benzil encapsulated PS-BDDMA resin

Figure 111.8. Scanning electron micrograph of PS-BDDMA resin Figure 111.9. Scanning electron micrograph of benzil encapsulated PS-BDDMA resin

(c). Encapsulation of OC-Diketones in the Cavities of EGDMA-Crosslinked Polystyrene g-diketone-encapsulated polystyrene was prepared by using ekhyleneglycol dimethacrylate as the crosslinking agent. &-diketone was dissolved in the diluent and the monomer mixture was mixed with it. The solution was suspended in PVA solution (MW.72000) and stirred mechanically. The precipitated polymer was washed with water and organic solvents. The encapsulation of benzil molecules in the cavities of PS-EGDMA matrix is represented in Scheme 111.5. Scheme 111.5. Synthesis of benzil encapsulated PS-EGDMA resin

under similar conditions. A slow release of the benzil molecules was observed in these cases. The intensity of the yellow colour of the resin decreased during these treatments but the IR spectra showed that the process of encapsulation was not severely affected by these treatments. The slow release of the benzil molecules may be due to the flexible nature of the crosslinking units under swollen conditions. The cavity sizes may be affected by the swelling process and thus the entrapped molecules liberated from the cavities. (d). Benzil-Benzilic Acid Rearrangement in the Cavities. of DVB-Crosslinked Polystyrene Networks bc-~iketone-encapsulated polystyrenes were subjected to benzil-benzilic acid rearrangement conditions. The benzil-entrapped polymers showed characteristic features of the covalently bonded polymeric benzils. The rearrangement was found to be facile in these heterogenized homogeneous systems. The polymeric product and the solution phase of the reaction mixture were analysed separately. Chemical analysis showed the presence of hydroxyl and carboxyl groups in the polymeric product. These functional groups were estimated by the usual methods. Resins with 2, 3, 4, 5 and 8% crosslinking were subjected to the rearrangement. The results of the functional group estimations are given in Table 111.5.

The benzil encapsulated resin was characterized by IR. A strong band corresponding to the carbonyl absorption of the diketo group was appeared at 1690-1700 cm-l. The IR spectra of PS-EGDMA resin and the corresponding benzil encapsulated resin are shown in Figure 111.10. The method of bulk polymerization was also applied for the preparation of benzil-encapsulated PS-DVB, PS- BDDMA and PS-EGDMA resins. In this method no diluent or suspension medium was needed. The guest molecules were dissolved directly in the monomer mixture. B ~ ~ Z O Y ~ peroxide was used as the initiator. The mixture was heated in a water bath at 80 c with stirring. The resulting polymers which are not in the bead form, can be collected after purification. Encapsulated polymers were tested for their stability under different conditions. The resins were stirred with dilute acids and organic solvents. PS-DVB resin with 2% to 4% crosslink densities are found to be stable under almost all the conditions. The entrapped benzil molecules were not eluted even after prolonged treatment with acids and organic solvents. The physical properties and the spectra are identical for the resins before and after these treatments. However, &-diketone encapsulated PS- BDDMA and PS-EGDMA resins were comparatively less stable

Table 111.5. Extent of benzil-benzilic acid rearrangement in the cavities of PS-DVB resin Crosslink Hydroxyl Carboxyl Resin density capacity capacity (mole %) (meq/g ) (meq/g ) 14a 2 2.2 2.4 14b 3 1.3 1.4 14c 4 1.7 1.7 14d 5 trace trace 14e 8 negligible negligible For the 5 and 8% crosslinked resins, the functional group capacities were almost zero. From the colour and IR absorptions of the precursor resins it was evident that there was no effective encapsulation of benzils within the cavities of these polymers. No rearrangement was observed in these resins. The hydroxyl and carboxyl group capacities of the three resins show that there is no regular relation between the crosslink density and functional group capacity. This is in contrast to the covalently supported polymeric benzils and benzilic acids. Moreover, for the highly crosslinked resins, the functional changes are not observable.

The rearrangement products of the 2, 3, 4 and 5% resins showed characteristic IR absorptions at 3400 cm -1 corresponding to the 0-H stretching vibrations. This arises from the tertiary alcoholic group of benzilic acid. A typical IR spectrum of the rearrangement product is given in Figure 111.11. Molecular rearrangements involve minimum spatial changes. The topographical properties of the polymer is little affected by the rearrangement of the encapsulated substrate. This is true in the case of the benzil- encapsulated styrene-dvb copolymer also. The scanning electron micrographs of the rearranged system (Figure 111.12) and its precursor are comparable. The solution phase of the reaction mixture was analysed separately. On acidification using dil. HC1, benzilic acid was precipitated. This arises from the diffusion of benzilic acid molecules from the cavities of the polymeric networks. A second possibility is the escape of benzil molecules under the rearrangement conditions and further rearrangement in the solution phase.

were employed for these studies. The hydroxyl and carboxyl groups in the product were estimated by chemical methods (Table 111.6). Table 111.6. Extent of benzil-benzilic acid rearrangement in the cavities of BDDMAcrosslinked polystyrene matrix Crosslink Hydroxyl Carboxyl Resin density capacity capacity (mole % ) (meq/g ) (meq/g The products were characterized by IR. A distinct peak was observed at 1680-1700 cm-' corresponding to the carbonyl absorption of the carboxyl group. The ester carbonyl peak was observed around 1720 cm-l. The peak observed at 3400 cm-i corresponds to the 0-H stretching vibration of the tertiary alcoholic group. (f). Benzil-Benzilic Acid Rearrangement in the Cavities of EGDMA-Crosslinked Polystyrene Matrix Benzil encapsulated in the cavities of ethyleneglycol dimethacrylate-crosslinked polystyrene was subjected to the rearrangement conditions. The resins with varying

crosslink densities were treated with potassium hydroxide. The products were collected by filtration and purified. The functionality of the resins was estimated and the results obtained are given in Table 111.7. Table 111.7. Extent of benzil-benzilic acid rearrangement in the cavities of PS-EGDMA resins Crosslink Hydroxyl Carboxy 1 Resin density capacity capacity (mole % ) (meq/g) (meq/g ) The extent of functionalization was found to be independent of the crosslink density here. Thus the amount of guest molecules entrapped in the cavities and the extent of functionalization within,the cavities are determined by the physical and morphological properties of the polymer. Upto a certain extent these properties are determined by the crosslink density. But factors such as temperature variation during the reaction, rate of stirring, surface tension of the suspension medium and other reaction variables are also important and often

dominant in many cases. Therefore the amount of functional groups entrapped in the cavities and hence the extent of the rearrangement are highly variable. Therefore the polymers do not exhibit any specific order in the extent of functionalization. The IR spectra showed a characteristic band at 3400 cm-' which was not present in the encapsulated precursor resin. The peak corresponds to the 0-H stretching vibrations of the &-hydroxy acid. From the investigations of the three encapsulated resins, it appears that the %-diketone molecules encapsulated within the organized cavities of the polymeric networks undergo the typical benzil-benzilic acid rearrangement giving the benzilic acids entrapped in the cavities (Scheme 111.6). The foregoing results indicate that molecular encapsulation furnishes a method for introduaing the characteristics of functionalization' in crosslinked polymers without recourse to chemical modification. The functional species are immobilized by entrapment in the interior cavities of polymer networks and the polymer provide a microenvironment for the reactive sites. Thus the clustering of molecules is completely avoided and a state of high dilution was attained even at relatively

Scheme 111.6. Rearrangauent of encapsulated benzil molecules into benzilic acid high concentrations due to the hyperentropic effect. The functional group entrapped within the cavities of the polymer act as a typical polymer-supported substrate. These undergo polymer-anarogous functional transformations and molecular rearrangements. The stability of the encapsulated system is determined by the molecular size, charge and geometry of the guest molecules and also by the cavity dimensions within the polymer networks. Analysis of the liberated molecules indicates absence of any chemical bonding between the guest molecules and the polymer. The problem of true heterogeneity in the polymer supported reactions can be minimised by the method of encapsulation.

HOFMANN REARRANGEMENT IN CROSSLINKED POLYMERIC MATRICES