CHAPTER I1

BENZIL-BENZILIC ACID REARRANGEMENT IN CROSSLINKED

MACROMOLECULAR SYSTEMS

Control over reactivity, rate and specificity can be

attained in functional transformations of organic

compounds by attaching the reactive species on a polymeric

backbone. The polymer matrix is often intended as a label

for mechanistic investigations of polymer supported

organic reactions. Molecular rearrangements are governed

by a number of parameters characteristic of the substrate

and the environment. In polymer-analogous molecular

rearrangements, the polymer provides a unique

microenvironment for the rearrangeable functional. group

and thus participates in the course of the rearrangement.

The polymer can influence the mechanistic and kinetic

responses of the functional species by its characteristic

molecular property and topographical behaviour.

The base-induced transformation' of an OC -diketone

into an oC-hydroxy acid is one of the most important

molecular rearrangements in organic chemistry 137-140. The

reaction is recognized as the prototype of a general

class of rearrangements and has been the subject of

numerous synthetic and mechanistic investigations

including applications of tracer techniques with isotopes

of carbon, hydrogen and oxygen. The rearrangement has

been investigated in the case of aromatic, semi-aromatic,

alicyclic, aliphatic as well as in heterocyclic

&- diketones 141-150. In view of this generalized nature

of the benzil-benzilic acid rearrangement it was thought

of interest to examine the effects of possible

macromolecular constraints on the rearrangement. when

carried out in a polymeric environment or on a polymer-

supported system.

s his chapter deals with the investigations of the

rearrangement of PC-diketo systems attached to an

insoluble, crosslinked polymeric network through a

covalent bond and rearrangement of benzil units existing

as part of the chain of the soluble linear polymers. The

preparation of polymeric K-hydroxy compounds and the

effects of the polymeric backbone on the ext.ent of

reaction and oxidation of the benzoin analogue into the

&-diketone are subjected to detailed study. The study

centers mainly on the rearrangement of

polymeric &-diketones into g-hydroxy acids. The effects

of molecular level reaction parameters are discussed. The

role of the macromolecular backbone on the course of the

rearrangements is investigated in detail. The molecular

character, frequency of crosslinking units and the

swellability in solvents are the factors which deem a

thorough investigation in these cases. The migratory

aptitude is studied under different reaction conditions

and the possible role of the 'polymer effect' is

discussed.

Terephthalaldehyde (TPA) was subjected to self

benzoin condensation and the resulting linear polybenzoin

was converted to polybenzil 151f152. Facile benzil-

benzilic acid rearrangement was observed in these systems.

In polybenzil derived from TPA, the rearrangeable function

exists as part of the backbone itself, not as a pendant

group, (in contrast to the polymer supported systems) and

the rearrangement process demands a chain contraction

within the polymer backbone.

RESULTS AND DISCUSSION

Polymers have been designed to serve as a support

material by immobilizing the rearranging systems and to

provide a typical hydrophobic or hydrophilic environment

for the functional groups. The chemical and physical

participation of the matrix in the course of the

rearrangement is related to the so called polymeric effect

which in turn is related to the molecular character of

the monomers. Properties such as the polar nature and

hydrophilic-hydrophobic composition are dependent on the

molecular properties of the monomers and thus a proper

choice of the monomer can produce polymer supports with

different physicochemical properties. The structurally

different polymer supports can impart different

microenvironmental effect^ on the rearranging functional

species. Two different types of polymer supports were

designed to investigate the benzil-benzilic acid

rearrangement in polymer matrices.

1 (a). Divinylbenzene (DVl3)-Crosslinked Polystyrene (1)

Styrene-DVB polymers with different crosslink

densities were prepared by suspension polymerization. The

inhibitors were removed from the monomers by washing with

0.1 N sodium hydroxide and water. The monomers in the

required ratio were dissolved in toluene and the mixture

was suspended in water containing PVA (MW 72000) as the

stabilizer. Benzoyl peroxide was used to initiate the

free radical polymerization. The size of the polyrner bead

depends on the extent of dispersion in solution, the rate

of agitation and the temperature. When the polymerization

is initiated, tough, insoluble and almost co~npletely

spherj.ca1 crosslinked beads of the polymer precipitate

out. DVB is a rigid and non-polar crosslinking agent and

the polymer produced by the copolymerization of styrene

and DVB is hard, rigid and hydrophobic (Scheme 11.1).

Scheme 11.1. Preparation of DVB-crosslinked polystyrene

DVB-crosslinked polystyrene samples with crosslink

densities 2, 5, 10, 15 and 20 mole per cent were prepared.

These "crosslink density" percentages are not absolute;

the figures indicate the relative amount of the

crosslinking agent in the polymerization mixture. The

amount of built in crosslinking agent in the crosslinked

polymer cannot be exactly determined. The crosslinking

percentages were adjusted by varying the monomer-

crosslinker ratio. Commercially available DVB c:ontainS

about 55% polymerizable isomer and the rest is a mixture

of ethyl styrene and other isomers. This composition was

taken into account in the calculation of the weight

of DVB.

The polymer sample obtained by the c~polymer~zation

was purified by repeated washing with water, ethanol,

dichloromethane, acetone and the resulting beads subjected

to soxhlet extraction with benzene for 24 h. The beads

were dried at 10oOc, weighed and the IR spectra were

recorded using KBr pellets. The spectrum was compared

with that of authentic samples. The yields ofthe pxoducts

are given in Table 11.1.

Table 11.1. preparation of DVB-crosslinked polystyrene(1)

Crosslink Wt. of the monomer (g) Yield density ..................... (9)

% Styrene DVB

(b). Tetraethyleneglycol Diacrylate (TTEGDAI-Crosslinked Polystyrene ( 2 )

The intrinsic reactivity of a functional group

attached to a polymeric backbone is identical to that of

the low molecular weight analogue. But the

microenvironment created within the macromolecular matrix

can change the reactivity of the active site. A polar

polymeric support has been designed with TTEGDA as the

crosslinking agent. The styrene-TTEGDA copolymer thus

produced provides a different local environment for the

rearranging system and facilitates a comparison of the

effect of the molecular character of the two supports on

the extent of the rearrangement. This polymer system has

a flexible network due to the extended length of the

crosslinks (Scheme 11.2).

Scheme 11.2. I'reparation of TTEGDA-crosslinked polystyrene

PS-TTEGDA resin was prepared by solution

polymerization technique using CH OH-CHC1 mixture as the 3 3

solvent and potassium persulphate as the initiator. 5,

10, 15 and 20 percent crosslinked resins were prepared by

adjusting the monomer ratio. The resin was freed from all

low molecular weight impurities by soxhlet extraction and

characterized by IR spectral analysis. The results are

given in Table 11.2.

Table 11.2. Preparation of PS-TTEGDA resin

Crosslink Wt. of the monomer ( g ) Yield density ..................... ( g )

( % ) Styrene TTEGDA

2. Chloromethylation of the Polystyrene (Resins 1 and 2)

Functionalization of styrene-based copolymers

involves electrophilic substitution on the aromatic ring.

The first step of the polymer-analogous reaction series

employed for introducing a dicarbonyl system into the

polymer backbone is the chloromethylation of the aromatic

ring. The reaction was carried out using anh:ydrous

SnC14, as the Lewis acid catalyst and chloromethyl methyl

ether. Dichloromethane was employed as the solvent

(Scheme 11.3).

Scheme 11.3. Preparation of chloromethyl polystyrene

The chloromethylated resins (3a & 3b)were purified by

repeated washing or soxhlet extraction using suitable

solvents. The degree of chloromethylation was determined

by estimating the chlorine content. In the Volhards

method of chlorine estimation, the resin was equilibrated

with pyridine and the pyridinium chloride thus formed was

treated with silver nitrate solution in excess. AyCl was

precipitated and the excess AgN03 was titrate'd with

ammonium thiocyanate using ferric alum as the indicator.

The results are presented in Table 11.3.

Table 11.3. Chlorine capacity of PS-DVB and PS-TTEGDA resins

PS-DVB resin (3a) PS-TTEGDA resin (3b)

Crosslink Chlorine capa- Crosslink Chlorine capa- density ( % ) city (meq/g) density ( % ) city (rneq/g)

3. Synthesis of Polymeric Aldehydes (4)

An aldehyde functional group can easily be introduced

into the polymer matrix via chloromethylation. Resin 3

was purified by soxhlet extraction using chloroform. The

resin was dried and treated with dimethyl sulphoxide at

138Oc to convert the CH2C1 group into - CHO group

(Scheme 11.4).

Scheme 11.4. Preparation of polymeric aldehyde

Dimethyl sulphide was removed by repeated washing

with hot water and common organic solvents. 1:t was

subjected to soxhlet extraction using benzene. The

aldehyde function was tested by the 2,4-dinitro phenyl

hydrazine reagent. A bright orange colour was developed

in the resin beads. The extent of functionalization was

calculated by estimating the residual chlorine in the

resin. IR spectrum was recorded using KBr pellets and a

strong peak was observed at 1700 cm-l, corresponding to

the C=O stretching absorption. Results of the

estimations are given in Table 11.4.

Table 11.4. Capacity of polymeric aldehyde (4)

PS-DVB resin (4a) PS-TTEGDA resin (4b)

Crosslink Residual Aldehyde Crosslink Residual Aldehyde density chlorine capacity density chlorine capacity

( % ) (meq/g) (meq/g) ( % ) (meq/g) (meq/g)

4. Preparation and Characterization of Polymeric

Analogue of &-~ydroxy Ketone ( 5 )

The cyanide ion-catalyzed benzoin condensation of

aldehydes is one of the thoroughly investigated reaction

in organic chemistry. The reaction is an excellent

example for specific catalysis and perhaps for that

reason, was one of the early organic reactions subjected

to kinetic study at the beginning of the twentieth

century. The benzoin condensation was extended here to

polymeric aldehydes.

(a). Intrapolymeric Benzoin Condensation

The preliminary investigations of polymer-analogous

benzoin condensation were carried out using 2% DVB-

crosslinked polystyrene copolymer containing aldehyde

functions in the aromatic rings (resin 4a or 4b). The

pre-swollen resin was treated with KCN at 108-120'~~ and

the unreacted cyanide was removed by washing with water

and water-miscible organic solvents. The polymeric

aldehyde undergoes benzoin condensation giving the polymer

analogue of K-hydroxy ketone (Scheme 11.5).

KCn/ EtOH

Dioxane

~ H O ~ H O HC C I II OH 0

5a or 5b

Scheme 11.5. Intrapolymeric benzoin condensation

The product was characterized by IR spectroscopy. A

broad peak was generated in the region 3380-3440 cm-I

corresponding to the 0 - H stretching vibrations of the

benzoin analogue. Peaks at 1090 and 1270 cm-I originate

from the C-0 stretching and 0 - H deformation vibrations

respectively. The strong peak at 1695 cm-I is due to the

C=O stretching vibrations (Figure 11.1).

The benzoin analogue (5a & 5b) obtained by the

cyanide ion-catalyzed condensation of polymeric aldehyde

was also characterised by noise-decoupled C ~ ~ N M R

spectroscopy. The carbon atoms C7 and C8 of the benzoin

analogue show characteristic peaks (Figure 11.2).

The carbonyl carbon shows a distinct peak at 166.0

ppm. The peak at 86.2 ppm corresponds to the carbon atom

to which the hydroxyl group is bonded. The ring carbons

exhibit characteristic peak at 126 ppm.

(b). Crossed Benzoin Condensation Between Pol.ymeric Aldehyde (4a or 4b) and Substituted Benzaldehydes

A polymer containing benzoin units is obtained by the

crossed benzoin condensation between polymer-bound

aldehyde and benzaldehyde. A heterogeneous mixture of the

two aldehydes was treated with cyanide under optimum

reaction conditions. Three possible products are expected

as depicted in Scheme 11.6.

3-0 E ~ O H AH o

Scheme 11.6. Crossed benzoin condensation between polymeric aldehyde and substituted benzaldehydes

The self condensation between low molecular aldehydes

and crossed condensation between the polymeric aldehyde

and low molecular aldehyde (Step I and I1 in Scheme 11.6)

are observed to be facile. The cyanide ion readily

attacks the low molecular aldehyde resulting in the

formation of the "active aldehyde" intermediate species,

leading to the formation of 5c or 5d and low mo:lecular

benzoin. The mixture of the product was washed with

organic solvents like toluene, benzene, dichloro~nethane

and acetone. This removes the low molecular benzoin. The

polymeric benzoin analogue was collected, and dried under

vacuum. IR spectra show peaks at 3380-3440, 1680-1700,

1270, 1090 cm-l corresponding to 0-H stretching, C=O

stretching, 0-H deformation and C-0 stretching vibrations

respectively.

A series of substituted benzaldehydes were employed

for the synthesis of crossed benzoins. The advantage of

the mixed benzoins over the self condensation product is

the increased freedom of mobility of the reaction site due

to its less rigidity (Scheme 11.7).

H-C - C H-C- C I I I OH 0

I I I OH 0

I

HC-OH I

HC-OH I C=O

Scheme 11.7. Polymeric analogues of self and mixed benzoins: rigid and flexible systems

Ortho- and para- substituted benzaldehydes were

subjected to benzoin condensation and the hydroxyl

capacity was measured by acetylation. These results were

used to draw a correlation between the substituent effect

and extent of benzoin condensation (Table 11.5).

Table 11.5. Effect of substituents on the extent of P O ~ Y ~ ~ I : analogous mixed benzoin condensation

Low molecular Hydroxyl capacity Percentage aldehyde of mixed benzoin condensation

( meq/g ( % )

Benzaldehyde 2.6

0-chlorobenzal- 1.5 dehyde

P-chlorobenzal- 1.7 dehyde

Cinnamaldehyde 2.4

Anisaldehyde 2.8

0-nitrobenzal- 1.3 dehyde

P-methyl benzal- 2.6 dehyde

The yield of the benzoin units was low when ortho-

substituted benzaldehyde was used for the condensation.

Electron-withdrawing substituents were found to decrease

the extent of the condensation reaction. This could be

due to the steric and electronic destabilization of the

intermediate species and the resultant decreased

reactivity of the species to attack the carbonyl carbon of

the polymeric aldehyde.

Various substituents were introduced into the

polymeric system through the low molecular benzaldehydes

in order to study the substituent effects on the extent of

polymeric benzil-benzilic acid rearrangement. From these

observations it appears that, the polymer-analogous

benzoin condensation is also sensitive to the electronic

and steric participation of the various substituents

present in the low molecular part of the mixed benzoins.

A weight increase approximately corresponding t.o the

molecular weight of the low molecular aldehyde was

observed during the course of mixed benzoin condensation.

(c). Effect of Crosslinking on Polymeric Benzoin Condensation

DVB-crosslinked polystyrene and TTEGDA-crosslinked

polystyrene (2, 5, 10, 15 and 20 per cent crosslink

densities) with aldehyde groups in the aromatic ring were

subjected to intrapolymeric benzoin condensation. The

reactions were carried out under identical conditions and

the benzoin units were estimated by chemical methods. The

percentage condensation was calculated and the feasibility

of the reaction was observed to decrease gradually with

increasing crosslink density (Table 11.6).

Table 11.6. Effect of crosslinking on benzoin condensation in crosslinked po:lymeric systems

PS-DVB resin PS-TTEGDA resin

Resin Cross- Percent- Resin Cross- Percent- No. link age con- No. link age con-

density densation density densation ( % ) ( % ) ( % ) ( % )

These results show a regular gradation in the extent

of condensation with crosslink density in the case of the

PS-DVB resin. Comparatively high benzoin capacity was

expected for PS-TTEGDA resin due to its flexible nature

and easy accessibility of the cyanide ion for the atldehyde

function. But the results show that in many cases the

percentage condensation is less in the case of PS-TTEGDA

resin compared to PS-DVB resin with the corresponding

crosslink density. These observations are explainable on

the basis of the chain length of the TTEGDA crosslinking

units. Due to the flexible nature of the crosslinking

units, the coiling of the polymer chain is not intensive

and thereby the aldehyde functions are spaced far apart.

Under these circumstances, due to the increased distance

between the reactive sites, a state of high dilution is

attained and the aldehyde groups are less prone to the

condensation reaction.

On the other hand, in the PS-DVB resin, the reactive

sites are rigidly held in the backbone due to the well-

defined morphology of the resin. DVB is more rigid than

TTEGDA crosslinks and the aldehyde groups are more closer

in the backbone. Therefore benzoin condensation is more

feasible in this polymer system.

(a). Effect of Hyperentropic Factor on Intrapolymeric Benzoin Condensation

The proximity of the pendant aldehyde groups bonded

to the phenyl rings in the polymer matrix is a decisive

factor which controls the extent of benzoin condensation.

The facile intrapolymeric benzoin condensation gives

evidence for the effective site-site interaction in

polymer-bound aldehydes. This was again tested by

preparing polymeric aldehydes with varying functional

group capacity. The resulting aldehydes were subjected to

benzoin condensation under identical reaction conditions

and the extent of intrapolymeric benzoin condensation was

estimated. The results show a linear relationship between

the functional group capacity of aldehyde and hydroxyl

value of benzoin (Figure 11.3). This gives evidence for

the effective site-site interaction in crosslinked

polymers. Otherwise, no intrapolymeric benzoin

condensation is possible in the case of aldehydes with

very low functional group capacity.

0 1 2 3 4 5

-CHO Capacity (meq/g)

Figure 11.3. Effect of hyperentropic f act(or on intrapolymeric benzoin condensation

5. Synthesis of Polymeric Diketones (6)

A diketo group was introduced into the polymer matrix

by oxidising the &-hydroxy ketone (resin 5a, 5b, 5c or

5d) using nitric acid as the oxidising agents. The yellow

colour of the benzoin analogue was intensified during

oxidation. In a second method resin 5 was treated. with

copper (11) acetate, ammonium nitrate and aqueous acetic

acid. The product was purified by repeated washing until

it is free from the last trace of acid. Polymeric

analogues of benzil (6a-6d) were obtained in almost

quantitative yield (Scheme 11.8).

H-C - C I OH

II 0

Scheme 11.8. Oxidation of polymeric analogue of benzoin into benzil

The IR spectrum shows a strong band at 1700 crn-I

corresponding to the C=O stretching vibration. The

spectrum appears as a single peak in this region with a

shoulder. This observation suggests a trans configuration

for the dicarbonyl groups. Therefore both the carbonyl

groups are not IR active. This configuration is

attributable to the rigidity of the polymer backbone and

the resulting spatial strain. The strong band in the

region 3440 cm-l which was present in the benzoin analogue

disappeared (or diminished) during oxidation

(Figure 11.4).

"1 3 C' CP-MAS spectrum was also used for monitoring the

benzoin-benzil conversion. The peaks at 173.6 ppm and

194.2 ppm were assigned to the carbon atoms of the

dicarbonyl group. The peak at 194.2 ppm is entire1:y a new

peak and was not present in the benzoin analogue (Figure

11.5). This shows that the carbon (C7) to which the

hydroxyl group is bonded in the benzoin analogue is

converted to a carbonyl carbon. The presence of well

separated peaks at 173.6 ppm and 194.2 ppm correspond to

the carbonyl carbons show an environmental difference .of

the carbon atoms. This appears to be imparted by the

backbone material.

The unreacted hydroxyl group in the benzil analogue

was estimated by acetylation method. The rearrangeable

diketo function was calculated from these results.

Benzil-Benzilic Acid Rearrangement in Crosslinked

Polystyrene Networks

The diketo resin was subjected to benzil-benzilic

acid rearrangement under basic conditions. The pre-

swollen resin was treated with potassium hydroxide and

absolute ethanol at 1 2 0 ~ ~ . A gentle and constant magnetic

stirring was applied throughout the course of the

reaction. The hydroxide ion attacks the carbonyl carbon

of the diketo group and the resulting species undergoes a

benzil-benzilic acid type rearrangement (Scheme 11.9).

'm C- C *-@$ C - C-OR -'@ II I I I I I / \ 0 0 0 - 0 0 - C-OR

I\ 0

'C"

HO / 'COO-

Scheme 11.9. Polymer-analogous benzil-benzilic acid rearrangement

The potassium salt of the & -hydroxy acid was

treated with HC1-dioxane mixture and stirred at room

temperature. The free acid was washed with water and

dried. The resin shows the characteristic tests for an

organic acid. The carboxyl group was estimated by

equilibrating a weighed quantity of pre-swollen sample

with standard sodium hydroxide at room temperature. The

hydroxyl group was also estimated and the results obtained

from the estimation are agreeable .with that of the

carboxyl values.

The IR band in the region 3380-3440 cm-I which was

present in the benzoin analogue and disappeared on

oxidation, reappeared during rearrangement. The resin was

analysed at different time intervals of the reaction and a

gradual reappearance of the peak was observed. This

corresponds to the 0-H stretching absorption of the

tertiary hydroxyl group. The shoulder of the C=O

stretching band which was present in the benzil analogue

in the region 1680-1700 cm-I disappeared during the course

of the rearrangement. However, the carbonyl absorption

remains strong and intense in this region with a small

shift to the higher wavenumber region. The C-0 stretching

and 0-H deformation absorptions also reappeared during the

rearrangement. A typical IR spectrurn of polymeric

analogue of benzilic acid to (7) is given in Figure 11.6.

The carbon atom bonded to the hydroxyl and carboxyl

groups shows a characterisitc peak at 89.2 ppm in the

c13 NMR spectrum (Figure 11.7) . The peak at 194.2 ppm in

the benzil analogue disappeared and. the peak at

173.6 ppm was shifted to 166.6 ppm. The low-field shift

of the carbonyl carbon clearly indicates the generation of

-COOH group from dicarbonyl group 153-156. The results are

in accordance with the results obtained from chemical

analysis and IR spectra.

The chemical and spectral analyses give conclusive

evidence for the intrapolymeric rearrangement. The

reaction was observed to be facile in the crosslinked

networks inspite of the environmental constraints imposed

by the rigid, crosslinked, high molecular weight polymeric

backbone. However, the possibility for the complete

detachment of the migrating group from the migration

origin during the rearrangement can be ruled out. If

complete bond breaking occurs before the bond formation

with the migration terminus, it would be difficult for the

bulky polymeric moiety to migrate to the carbon atom.

Therefore, it appears that the rearrangement involves a

cyclic transition state, with bond breaking and bond

formation taking place in a single step (Scheme 11.10).

C - C

0 0 II i l 0 0

'@+\q$i 5 +q C C / \

SO-?' KO-C OH HO- C I I ' 'OH II

0 0 0

Scheme 11-10. Mechanism of polymeric benzil-benzilic acid rearrangement

(a). Effect of Substituents

A series of polymeric 1,2-diketones with different

substituents in the aromatic ring were prepared by the

oxidation of mixed benzoins. Merrifield resin was used as

the matrix. These resins were subjected to benzil-

benzilic acid rearrangement under identical conditions.

The hydroxyl and carboxyl capacity of the resins were

estimated and compared. Results of the preliminary

investigations are given in Table 11.7.

Table 11.7. Hydroxyl values in polymers 5c, 6c and 7c and carboxyl capacity of resin 7c

Structure Reaction Temp. Hydroxyl value (meq/g) Carboxyl of time ....................... value of

diketone (h) (OC) Benzoin ~enzil Benzilic benzilic acid acid

5c 6c 7c (meq/g )

Facile rearrangement was observed in these mixed

diketones also. It was also observed that the reaction

conditions like the extent of reaction and temperature are

less rigorous in the case of mixed benzils than those

required in the case of benzil obtained by self-

condensation. The system is less rigid and the reactive

sites are more exposed to the reagent. Hence the

reactions are more feasible in such cases.

The rearrangement of mixed benzils also follow the

same mechanism as shown in Scheme 11.11.

Scheme 11.11. Mechanism of the rearrangement of mixed benzil into benzilic acid

Mixed diketones with o-chloro, p-chloro, p-methyl, p-

methoxy, o-nitro groups and some other groups as the

substituents were subjected to rearrangement. The effects

of the substituents were investigatd based on the

percentage migration of the diketone. The percentage

migration, in each case, was calculated from the

rearrangeable diketo groups and the hydroxyl and carboxyl

capacity of the rearranged product. The results are

given in Table 11.8.

Table 11.8. Effect of substituents on polymer-analogous benzil-benzilic acid rearrangement

Structure of the diketone

Hydroxyl Diketo Hydroxyl Percentage capacity capacity capacity migration of benzoin of benzil of benzi-

lic acid 5c 6c 7 c

(meq/g ) (meq/g ) (meq/g ) ( % )

These results indicate that the' ortho effect is

prominent in polymer analogous molecular rearrangements.

Polymeric benzil with o-chloro substituent gives only

37.8% migration whereas the corresponding para-compound

gives 63.7% migration. Ortho-nitro compound shows only

41.6% migration. This can be explained on the basis of

the steric participation of the ortho substituent which is

not favourable for the rearrangement since the formation

of a new covalent bond between the migrant and the

migration terminus is hindered.

Diketones with electron donating substituents were

observed to give comparatively high yields of the product.

The +I effect of the methyl and methoxy groups favours

the attack of migrant to the cabonyl carbon which is the

migration terminus. Thus, diketones with p-methyl and

p-methoxy groups showed 94 .0 and 88.5 per cent migration

respectively. Diketone without any substituent in the

phenyl ring gives 90.4 per cent migration.

However, the studies of the substituent effect on the

extent of polymer-analogous benzil-benzilic acid

rearrangement do not indicate any regualr trend in the

electronic effects of substituents. For example, the +I

effect of the -OCH3 group is larger than that of the -CH3

group. But diketone with methyl substituent gives 94.0

per cent migration whereas the corresponding methoxy

systems gives only 88.5 per cent migration. These results

suggest that the molecular level reaction parameters are

subject to complications by the inestimable polymer

effecl..~ arising from the complexity of the crosslinked

systems.

(b). Effect of the Nature of Crosslinking

The molecular characteristics of the crosslinking

agents like its polarity, hydrophilicity and rigidity

were found to affect the migratory aptitude of the

rearrangeable functions. For a comparative study, two

different types of polymer supports were employed. PS-DVB

resin is a typical hydrophobic polymer with rigid

crosslinking units. On the other hand, PS-TTEGDA resin is

a hydrophilic and polar polymer support with flexible

crosslinking. The diketo group was attached to both the

polymers and subjected to rearrangement under identical

reaction conditions. Dioxane was used as the solvent for

PS-TTEGDA resin whereas toluene was used as the solvent

for PS-DVB resin. The results are presented in

Table 11.9.

Table 11.9. Effect of the nature of crosslinking on the rearrangement

Crosslink Crosslinking Duration Solvent Percentage density agent of reaction migration

( % ) (h) ( % )

DVB 75 Toluene 82.3 5

T T E G D A 6 0 Dioxane 85.2

DVB 7 5 Toluene 74.0 10

T T E G D A 6 0 Dioxane 75.0

DVB 7 5 Toluene 54.5

'TTEGDA 6 0 Dioxane 60.0

85.2 per cent migration was observed in 60 h for 5%

PS-TTEGDA resin. But for 5% PS-DVB resin only 82.3 per

cent migration was observed in 75 h duration. This was

the case with resins of 10 and 15 per cent crosslink

density. The results are explainable on the basis of the

crosslinking pattern of the two polymer networks. The

reactive sites are buried deep in the rigid polymer

network in the case of PS-DVB resin and the diffusion

controlled movement of the hydroxide ion into the interior

of the polymer is difficult. But the reactive sites are

more available to the reagent in the case of PS-TTEGDA

resin due to its less rigid nature.

(c). Effect of the Degree of Crosslinking

The microenvironmental effect of the polymeric

backbone on the extent of migration of the rearrangeable

functional group attached to it is determined by the

frequency of crosslinking units within the matrix. A

correlation between the percentage migration and extent of

crosslinking was obtained using two 'different polymer

supports with varying crosslink densities.

PS-DVB resin with 2, 5, 10, 15 and 20 per cent

crosslink densities were prepared and converted to the

corresponding benzil analogues by a series of polymer

analogous reactions. Benzaldehyde was used for preparing

mixed benzoins. Rearrangement was carried out under

identical conditions using toluene as the solvent. The

percentage migration was calculated by chemical methods.

Typical results are given in Table 11.10.

Table 11-10. Effect of the divinylbenzene content on the extent of rearrangement

Crosslink Hydroxyl Diketo Hydroxyl Percentage density capacity capacity capacity migration

( % ) of benzoin of benzil of benzi- lic acid

5c 6 c 7 c (meq/g) (meq/g ) (meq/g) ( % )

Diketo function was introduced into the hydrophilic

PS-TTEGDA resins with 5, 10, 15 and 20 per cent crosslink

densities. Polar solvents like dioxane is more compatible

to the polar polymer matrix and the reaction is carried

out in dioxane under identical conditions. The &-hydroxy

acid formed by the rearrangement was estimated. The

results are given in Table 11.11. Hydroxyl groups

obtained by the partial cleavage of the ester functions of

a few crosslinking units were exempted from the

calculations.

Table 11.11. Effect of the tetraethyleneglycol diacrylate content on the benzil-benzilic acid rearrangement

Crosslink Hydroxyl Diketo Hydroxyl Percentage density capacity capacity capacity migration

( % ) of benzoin of benzil of benzi- lic acid

5d 66 7d (meq/g 1 (meq/g (meq/g 1 (%)

Diketo systems attached to PS-DVB and PS-TTEGDA

resins show regular decrease in the extent of

rearrangement with increase in crosslink density. 2% PS-

DVB resin gives 94.4% migration whereas 20 per cent PS-DVB

resin gives only 25% migration. The trend is similar in

the case of PS-TTEGDA resin also. Here the 5% resin gives

85.2% migration whereas the 20% matrix gives only 38.4%

migration.

These results can be explained as arising from the

increased rigidity of the polymer matrix and hence the

poor accessibility of the reagent to the reactive sites

rather than the steric participation of the polymer matrix

on the course of the rearrangement. The diffusion-

controlled penetration of the reagent into the interior of

the matrix is prevented by the high frequency crosslinks.

The decrease in the extent of rearrangement with the

increased degree of crosslinking is more prominent in the

case of PS-DVB resin due to the high rigidity of the

matrix. Hydrolysis of ester crosslinking units was

observed to some extent in the case of PS-TTEGDA resin.

Due to this hydrolytic reaction, unexpectedly higher

functional group capacities were recorded in the

estimation processes. Hence, a control experiment was

conducted in the case of PS-TTEGDA resin and this

functional group value was subtracted from the final

values (Table 11.11).

(a). Effect of Solvation

The effect of solvent on the course of benzil-

benzilic acid rearrangement was studied by using

1,2-diketo systems attached to a hydrophobic PS-DVB matrix

and a hydrophilic PS-TTEGDA matrix (resins 6c and 6d) . A

series of solvents with varying polarity were used for the

investigations. The rearrangement was carried out in

basic medium under identical conditions. The solvents

used for the studies are toluene, benzene, methanol,

water, THF and dioxane. The extent of rearrangement was

calculated in all the cases. Typical results are given in

Tables 11.12 and 11.13.

Table 11-12. Effect of solvation on benzil-benzilic acid rearrangement in PS-DVB matrix

Crosslink Percentage migration ( % ) density ...............................................

( % ) Dioxane THF Methanol Water Benzene Toluene

Table 11.13. Effect of solvation on benzil-benzilic acid rearrangement in PS-TTEGDA matrices

- - --

Crosslink Percentage migration ( % ) density ...............................................

( % ) Dioxane THF Methanol Water Benzene Toluene

Favourable interaction between the polymeric matrix

and the solvent is an essential factor for the effective

functionalization and functional group transformation in

polymer matrices. In polymer supported strategy, the

functional groups are anchored or immobilized on the

polymer support. These reactive sites are distributed on

the surface of the polymer beads or it may be buried in

between the crosslinks. If the polymer and solvent are

compatible, the movement of the reagent is facilitated by

the good swelling behaviour of the backbone and hence the

reaction rate increases. If the solvent and the polymer

are totally incompatible, the reaction is almost

inhibited. Benzene and toluene are found to be the best

solvents for the benzil-benzilic acid rearrangement in

hydrophobic PS-DVB networks (Figure 11.8).

PS-DVB resin undergoes effective swelling in non-

polar solvents like benzene and toluene. In a good-

swollen benzil analogue, the movement of the hydroxide ion

into the interior of the polymer is facilitated. This

favours the attack of the hydroxide ion at the carbonyl

carbon of the diketo system and hence the percentage

migration. PS-DVB resin does not show an effective

swelling in solvents like water and methanol and the

movement of the attacking species is hindered and thereby

the percentage migration is reduced. PS-TTEGDA resin, on

the other hand, shows poor swelling property in

0 5 10 15 20 25

Crosslink Density ( 8 )

Figure 11.8. Effect of solvation on the extent of benzil-benzilic acid rearrangement in DVB- crosslinked polystyrene matrix

hydrot'arbon solvents. However, it shows good swelling

behaviour in polar solvents like dioxane, THF and

methanol. PS-TTEGDA resin immobilized diketo systems

therefore undergo higher extents of migration in these

solvents (Fiyure I1 . 9 ) .

Crosslink Density ( % )

Figure 11.9- Effect of solvation on the extent of benzil-benzilic acid rearrangement in TTEGDA-crosslinked polystyrene matrix

Crosslinked polymers are macroscopically insoluble in

almost all the solvents. They can be solvated only to a

limited extent. This limited solvation also depends on

the molecular character of the polymer backbone. However,

by absorbing considerable amount of solvent, the

crosslinked polymeric network can expand largely and

become extremely porous forming a pseudo-gel. With

increased crosslinking, the polymer becomes more and more

rigid and free space in between the crosslinks available

for penetration of solvent is reduced. Thus the ability

for uptake of solvents is reduced. DVB and TTEGDA-

crosslinked polystyrenes represent two different types of

polymer supports with entirely different molecular

properties. The compatibility of the polymer with

different solvents is thus different depending on the

nature of the solvent. The migratory aptitude in polymer-

analogous molecular rearrangement is determined by the

characteristics of the solvents which influence the

swelling pattern of the matrix. In solvents which cannot

effectively swell the polymer network, movement or

diffusion of the reagent within the network to the

migration origin is difficult and hence the rate and

overall extent of the rearrangement are considerably

decreased.

7. Kinetics of Benzil-Benzilic Acid Rearrangement in

Crosslinked Polymeric Matrices

Standard kinetic analysis of polymer supported

reactions continues to be a challenging problem. Due to

the true heterogeneity of polymer supported reaction

systems, attempt to quantify the differences in reaction

rates between polymer supported reactions and its low

molecular analogues can be misleading. Moreover it may

not be accurate to speculate on possible mechanistic

difference between the homogenous and supported reactions.

Moreover diffusional limitation is imposed on reactions

occuring in crosslinked polymeric networks. All these

factors limit the utility and interpretation of kinetic

observations.

However, rate constants calculated based on the

probable rate equation can be used as a probe to

differentiate between reactivity under various reaction

conditions. Studies using easily swellable 5% TTEGDA-

crosslinked polystyrene matrix indicate that, benzil-

benzilic acid rearrangement in polymeric matrices follows

the second order reaction kinetics13'. Kinetics of the

rearrangement was followed in different solvents by

titrimetric method and the rate constants were calculated.

The k values are a measure of the solvation effect. The

rate constant values are given in Table 11.14.

From the results it is clear that dioxane is the best

solvent for benzil-benzilic acid rearrangement. In

dioxane medium, the observed k value was 3.08 x

-1 -1 (mole/litre) min . A gradual decrease in rate constant

values was observed with change in the polarity of the

solvent. The k value for the reaction in water is only

- 1 0.23 x (rnole/litre)-l rnin . The reactions were

Table 11-14. Rate constants of benzil-benzilic acid rearrangement in polymeric matrices

Solvent Solvent/water Rate constant ratio k

(mole/litre)-'min-'

Dioxane 2:l 3.08 x

THF 2:l 2.36 x

Methanol 2:l 0.81 x

Water - 0.23 x

carried out at the boiling point of the solvents and all

other reaction conditions were kept constant. Rate

constants were calculated by following the concentration

of potassium hydroxide present in the bulk phase

titrimeterically. Pre-swollen resin, rather than dry

resin is more suitable for carring out these studies for

getting consistent results.

8. Investigations of Salt Effect

Kinetic studies were carried out in presence of added

salts with different ionic strengths. It was observed

that the rate constants of polymer-analogous benzil-

benzilic acid rearrangement are sensitive to the presence

of these salts. KC1 and BaC12 with different

concentrations were employed for the studies. The kinetic

observations are presented in Tables 11.15 and 11.16.

Table 11-15: Salt effect on benzil-benzilic acid rearrangement in polymer matrices: Effect of KC1

Concent- Concent- Concent- k ration of ration of ration of (mole/litre)-' benzil KOH KC1 (meq/g ) (N) (N) mi n -1

Table 11.16: Salt effect on benzil-benzilic acid rearrangement in polymer matrices14 Effect of BaC12

Concent- Concent- Concent- k ration of ration of ration of (mole/litre)-l benzil KOIl BaC1

(N) (N) -1

(meq/g ) min

The kinetic picture of the benzil-benzilic acid

rearrangement in polymer matrices was complicated by the

addition of outside ions. KC1 or BaC12 increases the

ionic strength of the reaction medium and this increases

the rate. The effect is more pronounced with barium

chloride (Figure 11-10). The results are in accordance

with the positive salt effect observed in the

case of low-molecular weight benzil-benzilic acid

rearrangement 138,139

Figure 11.10- Salt effect on benzil-benzilic acid rearrangement in polymeric matrices

1.0 - 0 = KC1

= BaC12

0.8 -

* I 0 3 0.6 - \ Y

0.4 6

0.2- .

0 0.1 0.2 0.3 0.4 0.5

Concentration of the salt [N)

9. Molecular Rearrangements in Macromolecular

Solutions

The course of benzil-benzilic acid rearrangement in

insoluble crosslinked polymeric networks was discussed

earlier in this section. The effects of polymeric

backbone - its molecular character, frequency of

crosslinking and swellability were mentioned in this

connection. The preparation of a soluble polybenzoin from

a dialdehyde, its oxidation to the polybenzil and

rearrangement of the polybenzil into soluble &-hydroxy

acid by benzil-benzilic acid rearrangement are

investigated in this section.

The studies of molecular rearrangements in insoluble,

crosslinked polymeric matrices have some limitations due

to the heterogeneity of the system. The purification and

characterization of the product is difficult in these

systems. The interpretation of the results become

difficult in many cases. Such difficulties are largely

not there in the case of linear soluble, polymers. The

products are isolable with sufficient purity and

charactt:i~:ization is less difficult in these polymers.

(a). Synthesis of Polybenzoin ( 8 )

A polymeric analogue of benzoin was obtained by the

self-benzoin condensation of terephthalaldehyde. A

solution of the dialdehyde in dimethylformamide (DMF) was

subjected to benzoin condensation by using potassium

cyanide as the catalyst. A light yellow coloured

polymeria product was precipitated on acidification of the

reaction mixture. The last traces of the potassium

cyanide was removed by repeated washing with water. It

was expected that the dialdehyde undergoes a self-benzoin

condensation in presence of the cyanide ions

(Scheme 11.12).

OHC -Q CHO KCN Et OH/DHF II I

0 OH 0 OH

Scheme 11.12- Synthesis of polybenzoin from tere- phthalaldehyde

The product was characterized by spectral analysis.

IR spectrum was recorded using KBr pellets. The spectrum

shows characteristic peaks at 3440, 1680 and 1080 cm-I

corresponding to the 0-H str., C=O str., and C-0 str.

vibrations respectively.

NMR spectrum (Figure 11.11) was recorded in DMSO.

The polymer contains two types of ring protons with

different chemical and magnetic environment. This is due

to the presence of carbonyl and hydroxyl functional

groups in the molecule. 6 7.5-7.2 (m) and 6 8.1-7.9 (m)

correspond to the ring protons. 6 6.0 (s) is due to the -&H proton and 54.5-4.3 (s) corresponds to the hydroxyl

I

proton in the molecule.

(b). Synthesis of Polybenzil (9)

The polybenzoin obtained by the self-benzoin

condensation of TPA was oxidised to the correspondiny

polybenzil. The benzoin was heated with concentrated

nitril' acid. The secondary hydroxyl group was oxidised

into the carbonyl group. The reaction is depicted in

Scheme 11.13.

Scheme 11.13. Oxidation of polybenzoin into polybenzil

The precipitated polybenzil was washed repeatedly

with water to remove nitric acid. The products show

strong IR absorptions at 1700 cm-I corresponding to the

C=O stretching vibration. The band at 3440 cm-' which was

present in the benzoin analoguc disappeared during

oxidation reaction.

NMR spectral analysis gave some interesting results.

The spectrum (Figure 11.12) shows a peak at

68.18-8.01 (rn) corresponding to the ring protons. This

indicates the presence of only one type of ring protons.

The benzoin analogue showed two peaks ( 6 8.1-7.2) in this

region. This is due to the transformation of the

secondary alcoholic group into a carbonyl group resulting

the formation of a dicarbonyl system during oxidation.

Furthermore, the peaks at 66.0 (s) and 54.5-4.3 (s)

present in the benzoin analogue disappeared during the

formation of benzil. The -?H proton and hydroxyl proton I

disappeared during oxidation.

(c). Synthesis of Benzilic Acid (10) from Polybenzil: Benzil-Benzilic Acid Rearrangement

The benzil analogue was subjected to benzil-benzilic

acid rearrangement by applyiny the rearrangement

conditions. The resulting solution was acidified using

dilute HC1 and free benzilic acid was precipitated. From

the product analysis it is evident that, the rearrangement

was facile in these systems just like the rearrangement of

pendant gC-diketo systems. The reaction is depicted in

Scheme 11.14.

Scheme 11.14. Conversion of polybenzil from TPA into OC -hydroxy acid

The product was characterized by chemical and

spectroscopic methods. IR spectrum shows absorptions at

3450 cm-I corresponding to the 0 - H vibrations, which was

not present in polybenzil.

NMR spectrum (Figure 11.13) was recorded in DMSO.

10.1 (s) corresponds to the carboxyl proton. 8.1-

7.9 (in) and 6 4.4 (s) are due to the aromatic ring

protons and hydroxyl proton respectively.

The foregoing investigations indicate that a

rearrangeable functional group attached to a linear or

crosslinked polymeric support can undergo intramolecular

migrations under suitable conditions. The molecular

properties , and morphological characteristics of the

backbone are decisive factors in controlling the migratory

aptitudes. However, the rearrangement can be effected in

these macromolecular networks like any other solution

phase low molecular weight reactions. The effect of

molecular level reaction parameters and physical and

chemical nature of the polymeric matrix on the migratory

aptitude can be investigated. A systematic analysis of

the results offers a better understanding of the

mechanistic aspects of supported reactions and the

polymer effects .

MOLECULAR REARRANGEMENT IN MACROMOLECULAR CAVITIES