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).

F A + B @ - F

Encapsulation

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 P E G medium

(Figure 111.1).

For the control experiment constructed without adding

any P E G , the rate constant was 1.79 x lom4 (mole/litre)-'

-1 min 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

- 1 4.67 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 (mole/litre)-'

-1 min .

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 m i n

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 1 1 1 . 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

-1 to the C=O absorption apppeared at 1690 cm . 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 p o l y s t y r e n e s with different crosslink

densities were prepared in the presence of the guest

molecules. ~ e n z i l was strongly entrapped in t he networks

of PS-DVB resins w i t h 2, 3, 4 mole per cent crosslink

densities, Benzil molecules entrapped in t h e cavities of

resins with 5 and 8 mole per cent crosslink densities

esca2ed on repeated washing. This can be explained on t h e

Scheme 111.3.

11

Synthesis of benzil-encapsulated PS-DVB resin

(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-~ike tone-encapsu la ted 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 BDDMA- crosslinked 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