CHAPTER IV

HOFMANN REARRANGEMENT IN CROSSLINKED POLYMERIC MATRICES

The Hofmann degradation reaction has been used as a

synthetic route for the preparation of amines 180-187

Tanaka and Senju reported the Hofmann degradation of

p~lyacrylamides~~' Sodium hypochlorite was used as the

reagent and polyvinyl amine hydrochloride was isolated

almost quantitatively. The effects of reaction conditions

on the degradation reaction and the yield of amino

compounds were demonstrated in these studies.

Eldridge has reported the preparation of graft

polyvinyl amine by the Hofmann degradation of

polyaory1ami.de grafted to crosslinked polyvinyl alcohol

particles containing magnetic iron oxide 89,186-190. It

was observed that the conversion of amide to amine groups

was limited to about 25% and was accompanied by hydrolysis

and chain scission. Hofmann rearrangement of crosslinked

polyacrylamides as well as amide function attached to

styrene-based copolymers are discussed in this chapter.

Hofmann degradation reaction was carried out so as to

facilitate the preparation of polymeric amines and to

study the effect of various reaction parameters on the

extent of Hofmann rearrangement in polymeric networks.

This section deals with the preparation of polymeric

amides and its conversion to polymeric amine through an

intrapolymeric rearrangement. For the preliminary

investigations, 2% DVB-crosslinked gel-type polymer was

used. An amide function was introduced into the polymer

through the following steps: (i) Chloromethylation of the

resin (ii) Oxidation of chloromethyl polystyrene into

polymeric aldehyde (iii) Oxidation of aldehyde into acid

(iv) Conversion of acid into acid chloride and

(v) Reaction of acid chloride with dry ammonia giving

amide .

Rearrangement condition was applied and the products

were analysed. A temperature-dependent competition

between rearrangement and hydrolysis was observed.

Polyacrylamide resins with three different

crosslinking agents (in 5-20 mole per cent crosslink

densities) were prepared by copolymerization. The resins

were treated with hypobromite and the products were

characterised by chemical and spectroscopic methods. The

relation between the molecular character and extent of

crosslinking of the polymer and the extent of

rearrangement was derived in terms of the amino function

in the rearranged products.

RESULTS AND DISCUSSION

Preparation of Polymeric Amide from DVB-

Crosslinked Polystyrene

2% DVB-crosslinked polystyrene support was selected

for the preliminary investigations of the Hofmann

rearrangement in crosslinked polymeric matrices. The

support was prepared by the copolymerization of styrene

and divinylbenzene by the free radical suspension

polymerization technique using benzoyl peroxide as the

initiator. The macroreticular resin thus produced was

chloromethylated by treating with chloromethyl methyl

ether and SnC14. The chloromethyl polystyrene was

oxidised into polymeric aldehydes by treating with

dimethyl sulphoxide and sodium bicarbonate (Scheme IV.1).

For introducing a rearrangeable amide function into the

polymeric backbone, resin 4 was first converted into the

polymer analogue of aldehyde. The polymeric aldehyde was

treated with sodium dichromate in glacial acetic acid

containing a few drops of concentrated H2S04. Prolonged

heating and stirring is required for the effective

conversion of the aldehyde into the carboxylic acid. The

polymeric acid (17) was converted into the corresponding

acid chloride analogue (18) by treating with thionyl

191 chloride . For this purpose, resin 17 was thoroughly

dried in an air oven and swelled in benzene. The pre-

swollen resin was treated with SOC12. The apparatus used

were completely free from moisture and a calcium chloride

trap was used. The acid chloride thus produced was

converted into polymeric amide (19) by passing dry ammonia

after swelling in dried dioxane (Scheme IV.1).

DMSO CH2C1 -$ m c H O C1CH2nlg'm NaHC03 SnC14/CH2C$

Na2Cr207, CO OI-I

HAc

Scheme IV.l. preparation of polymeric amide

2. Synthesis of polymeric mine from Polymeric

Amide by Hofmann Rearrangement

Polystyrene supported amide was subjected to Hofmann

rearrangement. The resin was treated with sodium

hypobromite in strong alkaline medium. The reaction

temperature was varied from OOC to 70°c. The product was

washed with water and organic solvents. It was dried

under vacuum.

The resulting resin was subjected to chemical and

spectroscopic analyses. The rearrangement was observed to

be facile in these crosslinked polymeric matrices. The

amide undergoes a Hofmann type rearrangement yielding

polymer-bound amine as the product (Scheme IV.2).

Scheme IV.2. Hofmann rearrangement of polymeric amides into polymeric amines

The product polymer gives the characteristic tests

for primary amines. The amino capacity was determined by

the acetylation method. The extent of rearrangement was

calculated from the results. The percentage migrations

observed during these studies are less than expected. IR

spectral analysis shows that the carbonyl absorption of

the polymeric amide does not disappear completely during

the rearrangement. However, a slight shift was observed

to the longer wavenumber region (Figure IV.1).

The product was tested for the presence of acid

function in the resin. The carboxylic capacity was

determined by equilibrating a weighed quantity of pre-

swollen sample with standard alkali. The unreacted alkali

was estimated by titration with acid. The carboxyl

capacity was found to be higher than the amino capacity

(Table IV.l). These results indicate simultaneous

hydrolysis with the rearrangement.

3 . Rearrangement/Hydrolysis - Effect of Temperature

Hofmann rearrangement was carried out using DVB-

crosslinked polystyrene supported benzamide at different

temperatures varying from OOC to 70°c. The product was

isolated, purified and the amino and carboxyl groups were

estimated by chemical methods. Typical results are given

in Table IV.l.

Table IV.1: Temperature dependence of Hofmann rearrangement in polystyrene matrices: Competition between hydrolysis and rearrangement

Tempe- Capacity Amino Carboxyl Percent- Percent- Hydrolysis/ rature of amide group capacity age mig- age hyd- migration

ration rolysis ratio (Oc (meq/g ) (meq/g ) (meq/g ) ( % ) ( % )

39.5% rearrangement was observed at OOC whereas only

13.3% rearrangement occured at 70°c. 4 5 . 8 % hydrolysis

was observed at OOC and 68.75% hydrolysis was observed at

70°c. These results suggest a competition between the

rearrangement and hydrolytic reactions and the ratio of

these two reactions is temperature-dependent. The

percentage migration is inversely proportional to the

temperature whereas the percentage hydrolysis is directly

proportional to the temperature (E'igure'1~.2)..

At higher temperatures, the hydrolytic reaction is

dominant resulting in the formation of polymeric acids

(Scheme IV.3).

Figure IV.2. Rearrangement Vs hydrolysis

70 -

60 - 0 = Rearrangement = Hydrolysis

d# - E 0

.rl

u E 0 u X W

20 -

10 -

.

0 20 4 0 6 0 8 0 100

Temperature ( O C )

CONH

NH2

COOH

Scheme IV.3. Rearrangement Vs hydrolysis -

4. Synthesis of Crosslinked Polyacrylamide Resins

Differently crosslinked polyacrylamides (PA) were

192 designed for studying Hofmann rearrangement . In the

previous cases, the rearrangeable amide function was

anchored to the polystyrene support by a series of polymer

analogous reactions. The amide group w,as attached to the

support as a pendant group. Acrylamide on

copolymerization with crosslinking agents like DVB, TTEGDA

or N,N1-methylene bisacrylamide (NNMBA) gave the

corresponding crosslinked polymer network with amide

functions. These polymeric amides can be subjected to

Hofmann rearrangement.

(a). Synthesis of DVB-Crosslinked Polyacrylamide (21)

DVB-crosslinked polyacrylamide was prepared by

solution polymerization (Scheme IV.4) by using benzoyl

peroxide as the free radical initiator and ethanol as the-

solvent. The precipitated polymer was purified by soxhlet

extraction.

CONH

- CH2 - CH- -CH2 I

CONH2

-CH - CH2 - CH - CH2 - CH - C H y I I CONH2 CONH

21

Scheme IV.4. Preparation of DVB-crosslinked polY- acrylamides

DVB-crosslinked polyacrylamides with varying

crosslink densities were prepared by adjusting the molar

ratio of the acrylamide and DVB. PA-DVB resin with 5, 10,

15 and 20 mole per cent DVB contents were prepared. The

details of the copolymerization are given in Table IV.2.

Table IV.2. Preparation of PA-DVB resin

Wt. of monomers (g) Crosslink ...................... Yield

Resin density ( % ) Acrylamide DVB (9)

(b). TTEGDA-Crosslinked Polyacrylamide (22)

The polymerization was carried out at 60°c using

methanol as the solvent. The purified monomers were

dissolved in methanol and mixed with ammonium persulphate

as the initiator (Scheme IV.5).

PA-TTEGDA resins with 5, 10, 15 and 20 mole per cent

crosslink densities were prepared by adjusting the rat0 of

the monomers. The resins were purified by soxhlet

extraction technique. The details of the preparation of

the PA-TTEGDA resins are given in Table IV.3.

Scheme IV.5. Preparation of TTEGDA-crosslinked poly- acrylamide

Table IV.3. Preparation of TTEGDA-crosslinked polyacrylamide resins

Wt. of monomers (g) Crosslink ...................... Yield

Resin density ( % ) Acrylamide TTEGDA (9)

The resulting polymers were characterized by IR

spectroscopy. The IR spectra of PA-TTEGDA resins showed

absorption peaks at 1690 (C=O, arnide) and 1740 cm-I ( C=O,

ester). The appearance of the peak near 1740 cm-l (ester)

indicates the incorporation of the TTEGDA crosslinking

units in the polymer.

(c). Preparation of NNMBA-Crosslinked Polyacrylamide (23)

NNMBA-crosslinked polyacrylamide resins were prepared

by solution polymerization using water as the solvent

(Schme IV.6). Ammonium persulphate was used as the free

radical initiator and the reaction was carried out at

70°c. Crosslink densities were adjusted by varying the

acrylamide/NNMBA ratio. Resins with different crosslink

densities such as 5, 10, 15 and 20 mole per cent of the

bifuctional crosslinking agent were prepared. The details

are given in Table IV.4.

The precipitated polymers were purified by soxhlet

extraction and characterized by IR.

I CONH2 CO CONH I I I

Scheme IV.6. Preparation of NNMBA-crosslinked poly- acry lamide

Table IV.4. Preparation of NNMBA-crosslinked polyacrylamide

Wt. of monomers (g) Crosslink ...................... Yield

Resin density ( % ) Acrylamide NNMBA ( g )

23a 5 13.5 1.54 13.7

5. Hofmann Rearrangement in Crosslinked

Po1yacrylami.de Matrices

As part of the studies of molecular rearrangement in

crosslinked macromolecular matrices, Hofmann rearrangement

reaction in 2% DVB-crosslinked polystyrene supported

amide functions was investigated. About 40% migration was

reported in these studies. Formation of carboxylate

functions was also observed which appears to be due to the

hydrolysis of the amide groups. The investigations on

Hofmann rearrangement were extended into crosslinked

polyacrylamide resins. DVB, TTEGDA and NNMBA-crosslinked

polymers were used for these studies.

(a). Hofmann Rearrangement in DVB-Crosslinked Polyacrylamide Matrices

DVB-crosslinked polyacrylamide resins with different

crosslink densities were subjected to Hofmann

rearrangement. The rearrangement was observed to be

facile in these polymers which was established by the

analysis of amino group in the resulting product. The

polymeric amide undergoes a Hofmann type rearrangement

resulting in the formation of the polymeric amine

(Scheme IV.7).

NaOBr CONH2 I

NaOH

2 4

scheme IV.7. Conversion of polymeric amide into polymeric amine

Polyacrylamide resins with 5, 10, 15 and 20 mole per

cent crosslinking agent were subjected to Hofmann

rearrangement using sodium hypobormite. The amino group

was detected by usual chemical tests and the amino

capacity was determined by the estimation of the amino

group by acetylation method. The results are given in

Table IV.5.

Table IV.5. Hofmann rearrangement in DVB-crosslinked polyacrylamide matrices

Crosslink Amino Resin density capacity

(mole % ) (meq/g )

The results suggest that the conversion of amide into

amine is not quantitative. 5% crosslinked resin shows

2.79 meq/g amino capacity. For 20% crosslinked resin, the

amino capacity was only 1.51 meq/g. As the frequency of

crosslinking units increases, the extent,of rearrangement

was found to be decreased. The decrease in amino capacity

with increasing crosslink density is explainable based on

the polymeric effect of the backbone. As the DVB content

increases, the polymer becomes more rigid and hydrophobic

and the accessibility of the rearranging functional group

is reduced. In all the cases, carboxyl function was

observed in the product. This indicates the hydrolysis of

the amide groups into the carboxylic acid function as a

parallel reaction alongwith the rearrangement.

(b). Hofmann Rearrangement in TTEGDA-Crosslinked Polyacrylamide Matrix

The resins prepared by the copolymerization of

acrylamide and TTEGDA containing rearrangeable amide

groups were subjected to Hofmann rearrangement. The amino

group in the products obtained by the degradation reaction

was monitored quantitatively. The results are presented

in Table IV.6.

Table IV.6. Hofmann rearrangement in WEGDA-crosslinked polyacrylamide matrices

Crosslink Amino Resin density capacity

(mole % ) (meq/g)

In the case of PA-TTEGDA resin also, the extent of

rearrangement was found to be inversely proportional to

the crosslink density. 5% crosslinked resin gives 1.95

meq/g amino capacity whereas the 20% resin gives only 0.70

meq/g. This decrease is related to the increased rigidity

of the network and hence the decreased accessibility of

the reactive sites.

(c). Hoffman Rearrangement in NNMBA-Crosslinked Polyacrylamide Matrix

Hofmann rearrangement condition was applied to PA-

NNMBA resin with 5, 10, 15 and 20% crosslink densities.

The products were isolated and the amino capacity was

estimated by acetylation method. The results are given in

Table IV.7.

Table IV.7. Hofmann rearrangement in NNMBA-crosslinked polyacrylamide matrix

Crosslink Amino Resin density capacity

(mole % ) (meq/g )

Comparatively high amino capacity was observed in the

case of PA-NNMBA resin. The 5% resin gives 3.10 meq/g

amino group and the 20% resin gives 1.75 meq/g amino

capacity. This may be due to the partial bond scission of

the NNMBA crosslinking units in the polymeric networks.

Chemical and spectral analyses of the rearrangement

products of all the three different types of

polyacrylamide resins showed that there is no quantitative

conversion of the amide into amine through the

rearrangement step and the presence of some other

functional groups are also observed. Carboxyl group was

detected in all the cases, which might be produced by the

hydrolysis of the pendant amide groups or the amide

linkages of the crosslinking units. Good yield of the

amino functional group can be achieved by adjusting the

reaction conditions. The use of excess alkali facilitates

the rearrangement reaction. However the use of large

excess bromine will cause some side reactions. PA-TTEGDA

and PA-NNMBA resins are superior to PA-DVB resin due to

the polar character and accessibility of the crosslinking

units and hence the reactive sites to the attacking

species. But the ester and amide linkages in the

crosslinking units are labile for hydrolytic reactions.

Therefore, these resins are least preferred.

One of the important observations of the studies of

Hofmann rearrangement in polymeric matrices is the

dominance of the 'polymer effect' on the course of the

rearrangement. The purity of the Hofmann product was

doubtful due to the side reactions of the amide analogue

and bond scission of the crosslinking units. However the

polymer influences the extent of the reaction by its

topographical peculiarities. From the results of the

previous investigations with benzil-benzilic acid

rearrangement in crosslinked macromolecular systems, it

might be expected that the migratory aptitude in polymeric . analogous Hofmann rearrangement is dependent on the

crosslink density of the backbone and on the molecular

character of the crosslinking agents. Due to the

heterogeneity of the polymeric systems, the reagent

present in the continuous phase must penetrate into the

interior of the network to attack the reactive sites. As

the degree of crosslinking increases, the ability of the

reagent to penetrate into the interior decreases. This

will result in a reduced extent of migration in highly

crosslinked polymers.

The amino capacity of the rearranged product and the

extent of side reactions are different for the various

acrylamide resins. But in all the cases, an inverse

relation was observed between the extent of rearrangement

and the extent of crosslinking.

EXPERIMENTAL