Chemical modification of polymers. II. Attachment of carboxylic acid containing molecules to polymers

Reactive Polymers, 12 (1990) 133-153 Elsevier Science Publishers B.V., Amsterdam - Printed in The Netherlands

133

STATE-OF-THE-ART-REPORT

C H E M I C A L M O D I F I C A T I O N OF P O L Y M E R S II. A T T A C H M E N T OF C A R B O X Y L I C ACID CONTAINING MOLECULES TO POLYMERS * JEAN-CLAUDE SOUTIF and JEAN-CLAUDE B R O S S E

Laboratoire de Chimie et Physicochimie Macromol~culaire, Unitd de Recherche Associde au CNRS No. 509, Facult~ des Sciences, Universitd du Maine, Route de Laval, 72017 Le Mans (France) (Received July 29, 1989; accepted in revised form August 27, 1989)

The attachment of a molecule bearing an acid function to a macromolecular chain can be afforded by various types of linkages. Many of these are easily accessible and some can be reversible links. The ester linkage is specially well developed with hydroxylated polymers or non-hydroxylated polymers (especially epoxidized polymers) used as supports. Special attention is paid to the glycidyl group ( = 2,3-epoxypropyl) which has been introduced to various polymers, providing species with pendent expoxy arms. The catalysis, stereochemistry, secondary reactions, methods of evaluation of the epoxide content, spectroscopic characterization and the mechanism of the addition of acids to epoxides are reviewed

INTRODUCTION The first part of this review on chemical modification of polymers has illustrated with some examples the vast possibilities offered by this method of synthesis. The concept of chemical modification has been defined a s an application of traditional reactions of organic chemistry to macromolecules. Five main areas of interest are involved: • synthesis of copolymers not accessible by classical routes, • comparison of polymer modification/monomerization-polymerization, • aids to the analysis of the microstructures of polymers, • introduction of reactive sites along a polymer chain, and • fixation of active molecules (supported catalysts and reagents, phase transfer catalysts, supported synthesis, pharmacological use). The diversity of the methods of access to a given polymer is illustrated here by the attachment of acids to polymeric supports. * Part 1: Ref. [157]. 0923-1137/90/$03.50

© 1990 - Elsevier Science Publishers B.V.

134

The attachment of a molecule bearing an acid function to a macromolecular chain can be afforded by various types of linkages. Many of these are easily accessible and some can be reversible links. A special place is given to the ester bond, which is most frequently encountered and is accessible by many different methods.

1. M I S C E L L A N E O U S B O N D S

The amide bond, used by RJngsdorf [1] for chlorambucil *, requires the preparation of a polymer with lateral amine groups, followed by their condensation with carboxylic acid catalyzed by a carbodiimide. A succinimido derivative can also be used [2]:

b

{-~.~-,~-~]-. o

o

.....

~O

CO2H

~

O

The action of hydrazine on polymethyl methacrylate [3] has also been used, leading to a reactive polymeric hydrazide able to react with acids. The amide linkage has also been introduced in the chain by polycondensation of the N-carboxyanhydride of an amino acid [4] whose structure is close to that of chlorambucil:

°~"°~ °

[.co ..HI

I-""

.

OH2

N(CH2CH2(31)2

-[

1"

OH2

N(CH2CH2CI)2

Less frequently, the anhydride group has been obtained by a two-step modification of a crosslinked polystyrene [5] or directly from vinyl chloroformate [6]:

O

CI

Yo

" K2C03

O

~i

O-CO-R

0

Structures including oxazoline rings [7] can also lead to the immobilisation of acids on a polyacid-type polymeric carrier. One must however underline that esterification is the most favoured way. The following examples, classified according to the chemical nature of the polymeric carrier used for the * Systematic name: 4-{ p-[bis(2-chloroethyl)amino]phenyl} butyric acid.

135 modification, give a partial view of the different routes to obtain these polymers. The use of epoxidized polymers has been further developed in order to highlight different problems which are encountered in, for example, catalysis, mechanisms, kinetic studies, the influence of the microstructure, etc.

2. E S T E R L I N K A G E S a. Hydroxylated polymers a. 1 Direct esterification

Acid catalysis by p-toluene sulfonic acid, with azeotropic elimination of water resulting from the condensation, has been used to bind amino acids to poly(ethylene glycol) [8]. Also, molecular sieves allow good yields of esterification by improving water elimination. a.2 Acid activation

Anhydrides (for example butyric anhydride on dextran [9]) have seldom been used. The most frequently employed intermediates are acid chlorides [10]. The HC1 produced during the reaction can be removed by basic compounds such as: KOH (salicylic acid on starch [11]); N a O H in a Schotten-Baumann process (esterification of poly(vinyl alcohol) by photosensitive acids [12]); N, N-dimethyl aniline (2,4-dichlorophenoxyacetic acid on poly(2-hydroxyethyl methacrylate [13]); pyridine (esterification of poly(vinyl alcohol) by butyryl chloride [14]); or dimethylformamide (DMF) (for p-aminosalicylic acid on poly(vinyl alcohol) [15]). Alkyl chloroformates are boundary cases of acid chlorides and provide a convenient method for the attachment of alcohols to hydroxylated polymers. [16-19]. Carbodiimides [20,21], ion exchange resins [22] and also imidazole or benzotriazole derivatives [23,24] can be considered as acid activators:

~N

CO

CO

I

(I)

4"W4"-H CO CO

(I)

I

.

I

l

Although it cannot be compared directly with activation processes, the synthesis of intermediate reagents allows the attachment of acids to: • polysiloxanes [25]: CH 3

' CH3

CH3

CH3

+i,_o+

+

H

(CH2)2

I

CH3-Si- CH3 I

CH2 "O-CO-R

136

• polyacids [26]:

. o.O

CO2H

CO'O--CH2-CHOH

"c°~-°'~o+ ,/~1_o

,/3Lo

OH

-o-co-

OH

Ketenes with poly(vinyl alcohol) [27] or amylose [28] lead to/3-ketoesters:

OH

O-CO-CH2-CO-CH3

O

a.3 Transesterification Transesterification allows, for example, the attachment of palmitic acid to starch [29] or p-aminosalicylic acid to poly(vinyl alcohol) [30]:

H2N

CO2CH3

+

"'

O

OH

NH2

This reaction has also been successfully accomplished between acid and an unsaturated ester [31] for the synthesis of polymerizable derivatives of di- and trichloro phenoxy acetic acids: R-CO2H + CH3CO2-CH=CH 2 ~ R - C O 2 - C H = C H 2 Reactions analogous to the alkylation of acids, such as the grafting of poly(methyl methacrylate) [32] or carboxy-terminated polystyrene [33] on mesylated cellulose acetate are also known:

CH2"O'SO2CH3

~.co;

÷

I

CH2'O ~ CO-R

'

I

I

OAc R-CO2H=

w~,~CO2H

OAc or

~

"~'~"

Ph

CO CH3-O/

CO2H

137

b. Non-hydroxylated polymers b. 1 Halogenated derivatives Alkali metal salts of acids react with halogenated derivatives leading to the formation of the corresponding esters: X(CH2CH20)r ] CH2CH2X

R-CO2Na

,,

R-CO2-(CH2CH20 ) ~:~CO-R

CI Cl,~CI

Nat ~ ~ l ( = R-CO2Na)

CH2,-CI

CH2-C[

0 CH2 O-CO-R

No_oo_

PTC

R )/

Silver salts of carboxylic acids, investigated for the synthesis of methacrylates [37,38] have not yet been used to our knowledge for the chemical modification of halogenated polymers by acids. Crown ethers, often used in organic chemistry [39], should also be efficient for this type of reaction on polymers. The direct reaction of an acid with poly(p-chloromethyl styrene) to obtain a polymer containing N-substituted 5-(p-diethylaminobenzylidene)rhodanine in the side chain has been reported [40]:

~,"

~

~,c~S Jt S

It could be compared to the synthesis of poly(acyloxymethylglutamates) [41]: O -'3r-C - CiiH - N H

I (CH2)2 I

CO2H

]-- +

CI'CH2-O--C--R II O

DMF TEA

O II

--I--c-- C H - NHJI (CH2) 2 I

CO 2 - CH2 - O - - C ~ R II

O

138

b.2 Unsaturated polymers The addition of cinnamic acid to the carbon-carbon double bonds of polybutadiene has been accomplished with p-toluene sulfonic acid as a catalyst [42]:

O--CO-CH=CH--~

c. Addition of acids to epoxidized polymers The reaction of acids with oxirane rings leads to fl-hydroxyesters:

O

HO O--CO-R

This reaction usually needs less severe conditions than the preceding reactions. In solution and with a catalyst, the reaction temperature is usually between 60 and 100 ° C. Leading to numerous applications, its mechanism studies and catalysts have been described. This kind of support has also been used in the case of anhydrides [431 and acid chlorides [44]. The chlorine atom is then attached to the less substituted carbon atom:

~ ,

~ - - CH=CH-COCI O ~

0

o

o O_ o,

An early route to polymeric carriers of active molecules was provided by the chemical modification of epoxidized polydienes [45]. Other polymers such as synthetic polysaccharides prepared by epoxidation of poly(5,6-dihydro-2, H-pyran-6,2-diyloxymethylene) [46] can also be considered. The glycidyl group ( = 2,3-epoxypropyl) introduced onto various polymers provides species with pendent epoxy arms, for example on: • polysiloxanes [4?]:

H

Ptcatalyst

(CIH2)3 O \ ~O /

"4

139 • polyamides [48]:

+N.~"~ N~O. ~

co.}L Nal-VDMSO_{_N.~ N_CO.~O 4

R= -CH2-CHOH-CH2-O - ~ ~ - I ~

O- CH2 \CH -CH2 \ / O

• cellulose [49]:

H

OH

i

O~ /

OH

The second way of synthesis involves the use of a reactive monomer. Among the various examples encountered, three possibilities are schematized below: • a first route is offered by p-(epoxyethyl)styrene obtained from p-chlorostyrene which can be polymerized or copolymerized by a radical process [50]:

CI

MgCi

CHO

However, this monomer is quite difficult to prepare. 2,3-epoxypropyl vinylbenzyl ether, more easily obtained [51], has also been copolymerized with styrene. • epoxidized polyesters have been synthesized and further modified [52]. The oxirane group was on the diol moiety of the polyester. A diacid chloride bearing an oxirane ring is also accessible. This allowed the preparation of epoxidized polyamides [53,54]: O

O

,,

HC=CH ' HO-CO- J ~'~CO2H

HC--CH "HO-COJ ~,-,,-CO2H

'CI-COJ

CH ~"~ CO-CI

/ O\ -[- CO'OH--OH CO- NH- R - NH ]

The quite surprising inertness of oxirane with regards to the acid chloride group was explained by the electron-attracting effect of the substituents [54]. However, the polycondensates

140 synthesized have certain drawbacks such as a lack of stability concomitant with solubility problems. An epoxidized polyether has also been proposed [55]: 0~0

.

"[',o/~o--/"x.~/'~

-

"["o/Xo~ 0

In the methacrylate family, the species most investigated so far for pharmacological use (due to its low toxicity [56]), is glycidyl methacrylate. As a reactive monomer or comonomer, numerous chemical modification reactions, many of them involving acids [44,57-65], have been described:

\CO2-CH2

CO2-CH2

xCH__CH ~ \0 /

CO2-CH2

~CH--CH2

\CH__CH 2

X'Or

I I HO O~CO-R

The reactivity of the glycidyl group, an evident similarity with glycerides, the non-toxic spacer group it generates, and the polyacid-type support have justified the choice of this polymeric carrier for the attachment of acids with pharmacological properties. Glycidol and epichlorhydrin have been used as models for the study of the reaction. The addition compound with glycidol is also a product resulting from the release of the acid, with its spacer group, by hydrolysis of the polymeric carrier. Epichlorhydrin is another suitable reagent for the synthesis of intermediate products [66] for the attachment of acids on polyacids, as shown for indomethacin [26,67].

c.1 Catalysis The examples of catalysts found in the literature involve mainly reactions conducted on small molecules. However, catalysts can be used as well in the case of epoxidized polymers. Excepting for a few examples of acids [68] (sulfuric acid and phosphoric acid or p-toluenesulfonic acid) or their salts, alumina [69], a derivative of chromium triacetate [70], or chelates of chromium [71], most of the catalysts used for the addition of carboxylic acids to an epoxide can be classified as basic compounds. These include: potassium hydroxide [72], sodium hydroxide [73]; triphenyl phosphine [74]; trimethylamine [75] and various tertiary amines [76,77] (sometimes in the presence of chromium oxide, halide or acetyl acetonate [78]); quinoline [79] and pyridine [80] (sometimes as an ion-exchange resin [81]). Alkali salts are also effective [73]. However, their action could be explained by a reaction leading to a secondary product: / ~CH

\o /

CH

\ + X-,+M + R.-CO2H

"

/ CH-CH

+

R-CO2, + M

HO" \x

This effect should be compared to the reinforcement of the strength of acids by LiC1 observed in 'non-aqueous solvents [82].

141

D M F [83], dimethylacetamide [84] and hexamethylphosphotriamide (HMPT) [85], used as solvents and catalysts, can be related to the tertiary amine group. The formation of a quaternary a m m o n i u m by the addition of amine to expoxide [86,87] has been mentioned to explain the activity of teFtiary amines. The product resulting from the rearrangement of such a c o m p o u n d was identified during epoxystyrene polymerization initiated by 4-ethylpyridine [88]. A m m o n i u m halides have also been used [89-93], the nature of the halide having great influence [61,87], but a reaction similar to that mentioned for alkali halides cannot be disregarded: / ~CH

CH

\ + X-,+NR4 + R-CO2H

"

\o /

/ CH-CH

HO"

+

R-CO2-,+NR4

\x

Lastly, the synthesis of an anion exchange resin by the amination of glycidyl methacrylate copolymers by (CH3)3NH +, -C1 has been studied [94]. Different observations have led to suggest to use the salt resulting from the neutralization of the acid to be fixed by a tetraalkyl a m m o n i u m hydroxide [95] as a catalyst. This eliminates the ambiguity concerning the nature of the active species and avoids the formation of undesirable addition products. Among the possible a m m o n i u m derivatives, the simplest (tetramethyl) was chosen for its stability and availability. The benzyl trimethyl a m m o n i u m group has already been used as a catalyst [72], the a m m o n i u m salt then being produced in situ. Compared to the corresponding trialkylamine, the use of a tertiary a m m o n i u m salt can avoid some secondary reactions [96]. c.2 Stereochernistry Whereas the epoxidation by a peracid preserves the stereochemistry of the double bond due to the cis addition irrespective of the proposed mechanism [97-102], the opening of the oxirane ring by an acid involves a Walden inversion [95]. Moreover, with neutral conditions the nucleophilic attack involves almost exclusively the less substituted carbon [103]. The regioselectivity is reduced with the increase of the acid and oxirane steric hindrance [104], with the nucleophilicity of the acid [105], and depending on the stereochemistry of the oxirane ring [106]. This regioselectivity allows the synthesis of natural nucleoside analogues by addition of acids to the corresponding epoxides in H M P T [85]. However, during the one-step synthesis of glycol monobenzoate via the action of perbenzoic acid on an unsaturated c o m p o u n d [107], an example of configuration retention was observed with an aromatic substituent, and a phenonium ion was proposed for the transition state [108]: PhCOOO

I~'~ H~OH PhGO~~ Ph ." . . . Ph" GOCH3 H

Ph

IoQ

/

. . . . . .

OCH3

.H

. •

OCH3

c.3 Secondary reactions Besides the addition on the oxirane, some concurrent reactions are likely to occur with one or the other reagent. When acid stability is clear cut, only the esterification of the alcohols formed

142

during the main reaction can give rise to a decrease of the acid concentration independently of that of the oxirane: R-CO2-CH2-CHR'-OH + R-CO2H ~ R-CO2-CH2-CHR'-O-CO-R

+ H20

However, this reaction occurs usually at high temperatures with a strong acid as catalyst and leads anyway to acid immobilisation. For this reason, it is difficult to prove except on simple molecules [95]. A polymer study underlines the problem of the reliability of the method used to evaluate the epoxide decay. The results obtained during parallel dosage of oxirane and acid after the reaction on crosslinked copolymers of glycidyl methacrylate with sebacic acid in anhydrous medium (tetrahydrofuran) correspond to the attachment of more than two acid molecules per reacted oxirane molecule [109]. Moreover, it seems from the yield ( - 20%) that the hydroxyl formed (or initially present?) are more reactive than the oxiranes. The exact stoichiometry of the oxirane should in this case be regarded as suspect. The presence of water, formed in situ by esterification reactions or initially present in the solvent or the reagents, can lead to partial hydrolysis of the reaction products or of the oxirane, with formation of a diol: R-CO2-CH2-CHW-OH + H20 ~ R-CO2H + HO-CH2-CHR'-OH An anhydrous solvent is of course preferable to avoid this reaction. Nevertheless, many other reactions can affect the epoxide. Isomerization to allylic alcohol catalyzed by a tertiary amine [110,111]: O

(NR3)

..=

HO-CHz-CH~CH~OR

CH2-OR

or to a ketone in acidic medium [111] in the absence of a good nucleophile [112]: O

/\

--CH2-CH - - C H -CH2

CH2-1CI- CH2-CH2" g

O

leads to limitation of the level of acid immobilisation achieved. The addition of a hydroxyl group, the polymerization of the epoxide and all the related reactions (see hereafter) can involve several epoxidized units or their derivatives: O

R-CO,z-CHR'-OH

+

• X\ R

.

R-CO2-CHR'..O-CH2-CHR-OH

This reaction is associated with a faster decrease of the epoxide concentration than that of the acid. It is catalyzed by bases [72,110] like the addition of acid, and is competitive with the latter. It can induce the crosslinking of the product [113] when it occurs between two polymeric chains. It is generally considered as negligible [109] (the reaction of an acid on an epoxide can even be conducted in an alcohol used as the solvent [114]) or, on the contrary, as the main secondary

143

reaction [84]. Despite, the differences concerning the reagents and the reaction conditions, here again the stoichiometry can be considered as suspicious (HCI dosage [109] or methyl ethyl ketone procedure [84]). This reaction has been proved, however, on simple molecules [115]: COCH2CI ~

0

+ CICH2-CO2H '

"OH

+

0

In the case of polymers, this reaction could arise between two chains, though this is unlikely

[116]: 0 --CH

~CH 2

/\

CH2.

CHa-

+

,,

--CH 2 ~ 0

CH2-

0

I

N

0

">--4"\CH2 -

_ CH2

It is much more likely between two vicinal oxiranes on the same chain [117-120]:

dioxane

/ MeOH

0

On a small molecule a tetrahydrofuran ring has been identified [121]: OH

CH3(CH2 ) 5 ~ C H

2~

O

(CH2)7CO2CH3CI3CO2H O

THF

'

H O 5 , ~ j ~ CH3(CH2)

(CH2)7CO2CH3

The same reaction has been observed in an HCI catalysed reaction [122] and this is a serious drawback for the use of HC1 to analyse epoxidized polyisoprenes, for example:

It has also been seen with tetramethyl ammonium bromide [123]:

1 OH

O

O

144 This reaction occurs after a protonation of the expoxide and when the next unit is also an epoxide [124]:

[/

\]

"4-/

x-__/ M__

Similar reactions occur also with unsaturated units [125]:

All these reactions need extreme conditions, prolonged time and elevated temperature [116], and high hindrance to the penetration of the reagent.

c.4 Epoxide content The most often used methods involve the addition of HX (X = C1 or Br) to the oxirane ring [126] in aqueous solution or in alcohol saturated with MgC12 [114], in ether [127], acetic acid [1281, D M F [129], methyl ethyl ketone [84,130] (sensitive to acids and alcohols), or as pyridine hydrochloride. The excess of reagent is evaluated afterwards and the epoxide content obtained by difference with a blank. The reagent (HBr) can also be generated in situ by action of perchloric acid on ammonium bromide [131]. A study of the advantages and drawbacks of this method [132] points out some possible interactions with other functionalities such as carbon-carbon double bonds, alcohols [130] and amines [133]. Furthermore, the need for precision in the process has made it preferable to use in some cases vapour phase chromatography [112] for measuring the level of epoxide content, or indeed spectroscopy. These procedures are used, however, as references for other methods, degradation by periodic acid or lead tetracetate [134] and calorimetric (DSC) analysis [124]. Other methods involve the addition of a secondary amine [135] (sensitive to ketones and esters), the elementary dosage of oxygen [136] (but this cannot distinguish from other functional groups) or the formation of coloured derivatives with dinitrobenzene sulfonic acid [137] or amines [126], evaluated by colorimetry (very efficient for small quantities). However, all these methods also involve chemical modifications, with all the restrictions already mentioned. The presence of isomers with different reactivities, secondary reactions and the isomerization of the epoxide which decrease the reliability of methods available for pure products [126] can all present problems. Compared to chemical methods, IR [138] and ~H N M R [139] offer many advantages.

c.5 Spectroscopic characterization of epoxidized polymers aH N M R is obviously the best choice [124,139,140]. The signals of hydrogens located on the oxirane ring ordinarily appear between 2.5 and 3 ppm (up to 4 ppm for - C O - C H - O - C H - C O [53]) and those in the ~-position are displayed towards lower field positions'. With ~C N M R

145

[62,140-143] the chemical shifts are between 40 and 65 p p m according to the nature of the substituents and the stereochemistry of the oxirane. The characteristic absorptions in IR spectroscopy can be observed at 1250 cm -1, 840 cm -1 (cis) and 885 cm -~ (trans) [126], but this technique may indicate the presence of epoxide even when a chemical method is negative [144]. IR and near-IR have been used for the evaluation of epoxy resins [145], of glycidyl methacrylate copolymers [138] and of epoxidized natural rubber [123]. c. 6 Mechanism of the addition of acids to oxiranes A review of the different mechanisms proposed [76] points out the diversity of the conclusions, but it must be underlined that the reactions were realized under various conditions [146]. The protonation of the epoxide can easily be achieved with a strong acid (HCI [147]) or in the case of styrene oxide. The resulting form is then stabilised by resonance [148]. Phenomena of autocatalysis are sometimes observed in the absence of a catalyst [149]. The following examples concern only basic catalysis by tertiary amines or a m m o n i u m salts. A reaction mechanism is directly related to the reaction order observed with respect to each reagent, and to the nature of the intermediate activated complex and of the catalyst. The order with respect to the epoxide is in all cases one, but this is not always so for the acid and the catalyst [75,150]. The catalysis by amines has been explained in three different ways: • Their action allows the ionisation of the acid [72,150,151] in equilibrium with an intermediate complex (I): R'CO2H + NR3

o R'CO2(~) +

'

•

L-'NNR.

[ R'CO2H.... NR3 } (i)

O

~

O

R'CO2 + HNR3

oG)

I R'CO2H R'CO2-CHa-CH-R"

R'CO2-CHa-CHOH-R"

+

R'CO?

An order of ¼ (in bulk) or ½ (in dioxane) was observed with respect to the acid and to the catalyst [150]. The difference in the effect is explained by an equilibrium between associated pairs of ions and free ions [146]. A non-integer order, attributed to the coexistence of ionic and concerted mechanisms, was also found for a reaction in xylene solution [151]. • The concerted mechanism [77,79] involves the formation of an intermediate complex (II), whose structure is not always described [152], between the acid, the epoxide and the tertiary amine, after the formation of I by interaction of the amine with the acid. This complex allows the mechanism to involve the three reagents during the rate-determining step of the reaction, with a unit order with respect to the acid and to the amine: R" 11) +

0 / \

-~ NR"

r

/2-" IR'--C~, [

, ,O

111)O ' " "H,,

NR3

.

NR3 + R'CO2-CH2-CHOH-R"

146

A non-integer order is explained by the coexistence of the ionic mechanism [153] where the influence of the solvating power of the solvent can be important. The ionization of the acid by the amine, after a preliminary reaction of the latter with the oxirane, seems to prevail now:

NR3 +

(Ill)

o • ~XR"

+ R'CO2H

fast

fast

@ ® FteN-CH2-CHR"-O (111)

0

@

R,C02, R3N.CHzCHR._OH

The first step is also proposed for the addition of primary and secondary amines [154]. The c o m p o u n d III is proposed as the catalytic species, or as one of the catalytic species for the acid addition to the epoxide [58,62,80,87,114,155]. These two preliminary steps in addition to the normal reaction are supposed to be rapid, without any precise experimental data to confirm this. Generally the orders are not integer, due to the coexistence of parallel ionic and concerted mechanisms. Coexisting with acid catalysis, basic catalysis is sometimes supposed to explain a non-integer order with respect to the acid [80]. Despite some mathematical weaknesses encountered such as: surprising acceleration of the epoxide decay when the acid is totally reacted [72]; different order when the a m m o n i u m salt is formed in situ [87] or introduced into the medium; k determined in the 40% conversion zone without any justification of this choice [150]; arithmetic mistakes [151]; questionable simplifications: [-CO2H ] = [-CO2H]0 after 20 to 30% reaction [152]; and a equilibrium {-CO2H + amine [-CO2H --- amine]} displaced to the left by addition of acid [152], one must admit that each of the species mentioned exists in the reaction mixture. The degree of association between the acid and the amine has been indicated by IR for pyridine [152], and by tonometry, NMR, conductimetry and IR in the case of dimethyldodecylamine [76]. The formation of the addition product of tertiary amine has been proved and evaluated indirectly by the disappearance of the amine [80]. Intuitively, the formation of this addition product must be less easily reversible than the amine-acid association, and therefore it will prevail rapidly over the association. However, the coexistence of these two species, the association of solvated ion pairs and the formation of the complex explain the disparity of the observed reaction orders with the multiplicity of reaction conditions. No mechanism has been proposed when the catalyst is an a m m o n i u m salt. If one admits the possibility of anion exchange and the addition of the catalyst to the epoxide, the situation is then identical to the preceding case, and this justifies the use as catalyst of an arnmonium salt of the acid to be attached [95]. A study performed with a constant initial epoxide concentration or constant a c i d / e p o x i d e and catalyst/acid has shown that the increase of the acid concentration is accompanied by an increase of the conversion ( X ) of the epoxide. The value of the second-order kinetic constant k seems to be a linear function of the initial acid concentration a; the plot of X / [ c t ( 1 - X)] versus a (for a > 0.2mol 1-1) gives a straight line, but this does not pass through the origin. In fact, the application of a kinetic law with a reaction order of one with respect to each reagent, proposed in the case of a tertiary amine, does not take account of the nature of the different species existing in the reaction medium in the case of the a m m o n i u m salt, but allows the description by simple

147

relations of the influence of four reaction parameters: time, temperature, and catalyst and epoxide concentrations. The hypothesis of a unit order reaction with respect to the acid does not illustrate perfectly the reaction mechanism, but it allows a good representation of the acid conversion on the condition that the initial acid concentration is kept constant. The variation of the dielectric constant of the medium with the acid concentration has probably some influence [93], and an equilibrium between different species derived from the acid could be involved to explain this phenomenon, such as the existence of dimers, trimers, etc., but it is not sufficient to explain the results. A more precise mathematical description could only be proposed with the proposition of the corresponding mechanism. One must consider the proper reactivity of the catalyst with regard to the epoxide. The catalyst is in fact the ionised species of the acid to be attached. The reaction scheme should then involve an equilibrium between the catalyst and the epoxide on one hand and an addition product (designated by S in the following equations) on the other: (~ 1~ BOO2, N(CH3)4

0 '/ ~ R '

Jr"

k+ •

® R.CO2-CH2-CH(R')-O , NE~,Ha)4

k

S

®@

k

S Jr- RCO,2H

"

ds/dt = K+(c-s)(b-s-x)dx/dt = k.s(a-x)

FICO2-CH2-CHOH-R' -}-

k-.s-dx/dt

; [S] = s

;

RC02,

N(CH3)4

a = [acid]

; b = epoxide

; c = catalyst

The relation between s and t also depends on the ester concentration x, and this does not allow an integrated relation for x to be obtained. Due to the existence of parallel routes giving the ester, the use of a second-order law is the most simple way to represent the reaction kinetics. Some other methods for the treatment of the results obtained in the case of complex reactions have been reported [156].

CONCLUSION Amongst the differents methods used for the attachment of a molecule bearing an acid function to a macromolecular chain (amide, anhydride, ester), the ester linkage is most frequently involved when hydroxylated polymers and non-hydroxylated polymers (especially epoxidized polymers) are used as supports. The glycidyl group ( = 2,3-epoxypropyl) provides polymers with pendent epoxy arms and has been introduced onto various polymers. The review of catalysis, stereochemistry, secondary reactions, methods of evaluation of epoxide content, spectroscopic characterization, and mechanisms of the addition of acids to epoxides points out the diversity of the conclusions obtained from various reaction conditions.

148

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