The use of functionalized polymers as polymeric reagents in solid phase organic synthesis. A review

Reactwe I'olvmers. 8 (1988) 273-284

273

Elsevier Science Publishers B.V.. Amsterdam Printed in "[he Netherlands

T H E U S E OF F U N C T I O N A L I Z E D P O L Y M E R S AS P O L Y M E R I C R E A G E N T S IN S O L I D P H A S E ORGANIC S Y N T H E S I S . A REVIEW * AIIMED AKELAII

Chernist£v Department of Facult.vof Science. Tanta Unwersitv, Tanta (Egyptl (Received November 4. 1986; accepted in revised form September 8, 1987)

The application of functionalized polymers in solid-phase organic synthesis for soh,ing the problems which accompany con+'entional chemical reactions and for proeiding the possibility" of automation in chemical procedures is described. A brief description of the swlthesis of functionalized polymers and the effect of polymer structure and properties on their reactwi O" as well as an explanation of potential advantages and disadvantages of using polymeric reagents will also be discussed. The polymers" properties can be modified either by chemical reactions on pendant groups or hy changing the physical nature of the pol.vmers, such as their physical form, soh:ation hehaviour, porosiO', and stability. Such properties have a great importance for the functionalization reactions and for the eventual application of the reactive polymers, and must be considered during the design of a polymeric reagent, ltowever, all these properties in turn depend on the conditions employed during resin preparation and the degree of crosslinking of the resin as determined by the extent of swelling. Some examples will be described in order to deeelop the principles associated with the main utilization of functionalized polymers as polymeric reagents in solid-phase organic" synthesis.

INTRODUCTION

Reactive functionalized polymers have recently found widespread applications as reactive materials in a variety of biological [1,2] and other technological uses [3], based on the advantages of the functional groups and the

* Paper presented at the ESF Workshop on Reactive Polymers as Supports and Catalysts, Tirrenia. Italy. October 1-3, 1986. 0167-6989/88/$03.50

properties of the polymeric molecule. The use of reactive polymers in solid-phase synthesis [4-9] has also emerged as an attractive approach on a commercial industrial scale. This technique offers great promise in solving the problems accompanying conventional chemical reactions and for providing the possibility of automation by carrying out reactions in flow reactors. The aim of this article is to illustrate the principles and the basic framework relating the chemical structures and physical proper-

~+ 1988 Elsevier Science Publishers B.V.

274 ties of functionalized polymers with their reactivities in chemical modifications and in applications in organic synthesis, in an attempt to achieve the requirements for ideal polymeric reagents. Polymeric reagents are reactive functionalized polymers which are used to effect the chemical transformation of a reaction substrate to afford the reaction product, the polymeric reagent itself forming the polymeric by-product: A reactant +

B product +

®-x

, ®--v

polymeric reagent

polymeric by-product ~.~regeneration~

The polymeric reagent is usually used in stoichiometric amounts or in excess to increase reaction rate and hence to drive the reaction to completion to improve the yield. Their applications represent an important aspect of recent developments in organic synthesis. However, the comparison between the reactivities of the polymeric reagents and their analogues used in homogeneous reactions is not always simple, since the physical properties of the support can exert a strong influence on the performance of the reagent. The laboratory use of polymeric reagents has several considerable advantages, such as simplification of the procedure, automation, use of excess polymeric reagent, regeneration and reuse of polymeric by-product, reduced use of toxic and malodorous compounds, and increased stability of otherwise unstable reagents. However, their use on a commercial scale has met with drawbacks becoming apparent in industrial processes, such as high costs and the reduction of the degree of functionalization during regeneration. In addition, there are also some other disadvantages such

as slow reactions and low reactivities, low product yields, difficulties with separation of impurities, additional synthesis time, and restriction of the ultimate capacity of functionalization. Some of these disadvantages can be solved by a proper choice of the support.

PREPARATION POLYMERS

OF

FUNCTIONALIZED

The attachment of functional groups to the polymeric support is frequently the first step towards the use of reactive functionalized polymers for a specific application. In principle, the required active functional group can be introduced onto polymeric support chains either by (i) polymerization of monomers containing the desired functional groups, or by (it) chemical modification of preformed polymer [10,11]. Each of the two approaches has its own advantages and disadvantages. Although a proper choice of the polymeric matrix is an important factor for successful utilization of polymeric reagents, many types of readily available natural and synthetic polymers have been chemically functionalized for use as reactive supports. A wide range of inorganic supports [12] have also been modified and are suitable for various catalytic and chromatographic applications. However, they cannot meet the capacity demands of polymeric reagents as a result of their low loading capabilities. In addition, polysaccharides, with their very low cost, possess a functionality for derivatization and have also been functionalized for use as reactive polymers [13,14], as illustrated by the example given in Scheme 1. However, they have the significant disadvantage of being insoluble in solvents suitable for chemical modifications. They are also subject to biological and chemical breakdown of the matrix. These drawbacks are sufficient to limit their use as supporting reagents.

175 Cell--OH

:C,~ OCOCHpNEI 2 . . . . .

~C'~-- OCOCH2N÷Et2BJ Br-

20 % DS. 0 72 mmol/g

15 "/. DS, 0 37 mmol [g

I

Cell--OK

,,.j

L

OCOCH'2C I

........

~

,'C/r-- OCOCH c N÷ ( r l - - Bu ; C '-

30 */. DS, 129 mmol/g

,~C ~r"- O C O C H ~ C H 2

! /. :C ~

18 "/* DS, 0 4 7 mr'qol [g

OCOCH~ P * ( n - - B,J) . CI-

7 2 % DS,O 17 mmol/g

l

',,C~

O C O - - (CH 2 )z NEt2 33% DS, 114 mmol/g

~'~j~'-- OCO(CH.~):, N * E t : B u

Br"

29 % DS. 0 69 mmol/g

Scheme 1. Chemical functionalization of cellulose [14].

In spite of the widespread use of the polystyrene matrix as a support for reagents, based on its reactivity and stability relative to other types of synthetic polymers, poly(methyl methacrylate) (PMMA) resins have recently been prepared and chemically modified for utilization as supports for reagents and catalysts [15 17]. A wide range of crosslinked rigid spherical P M M A resins beads have been prepared by the well-defined suspension polymerization technique [18]. Polymer composition and polymerization conditions were empirically adjusted to produce a variety of structural characteristics desirable for various types of chemical applications. These conditions include appropriate adjustment of the monomer:diluent as well as monomer:crosslinker ratios to allow a variety of bead polymers to be generated, ranging from gel-type to macroreticular species. The selection of suitable diluents was determined by the solubility characteristics of linear PMMA. as summarized in Table 1: details of a number of prepared resins are shown in Table 2. This support has the advantage of having a polar character as well as a functionality for direct attachment or generation of a variety of functional groups. In addition it fulfills the major

requirements for an ideal support, such as (i) ease of preparation with controlled degree of crosslinking to give spherical porous beads, (ii) compatibility with most organic solvents, (iii) chemical and mechanical stability, (iv) inertness of the backbone towards reactants and reagents, and (v) low cost and commercial availability of the monomer. Modifications of the ester functions of P M M A by the replacement of the methoxy group with an amino group or by reduction were successfully carried out. The amination

TABLE 1 Solubility characteristics of methyl m c t h a c r y l a t e ( M M A ) , its linear h o m o p o l y m e r ( P M M A ) , and its copolymers with styrene (v/v#~, ratio) Solvent

MMA

PMMA

10%

20%

Benzene "]'oluene n-ttcxane Cyclohexane Methanol iso-Propanol n-Heptanol Cyclohexanone n-Pentanol

S S S S S S S S S

S S 1 I 1 I I S S

S S I I I I 1 S I

S S 1 I 1 I 1 S I

S: soluble, I: insoluble.

276 TABLE 2 Monomer phase composition Resin no.

DVB ratio v/v%

Ia

1

Ib Ic Id Ie If I8 Ih Ii

1 2 2 2 5 5 10 20

Diluent:monomer

and solvent

inhibition

data for PMMA

Diluent

resins, Ia-i

Swelling (g/g) Cyclohexanone

Toluene

Dioxane

Acetone

Water

_

0.31

0.88

1.57

0.76

_

Tol:i-PrOH(1:4) Tol:HepOH(1:4) Cyclohexanone: Cyclohexanone Tol:i-PrOH(1:4) Cyclohexanone: Cyclohexanone Cyclohexamone

1.35 0.41 1.49 1.42 0.65 0.51 0.43 0.77

0.73 1.12 1.80 1.42 0.35 1.09 0.78 0.97

2.14 3.57 244 _ 1.55 1.03 0.73

0.31 0.86 1.22 1.27 0.11 0.76 0.35 0.31

0.20 0.55 0.81 0.0 0.29 0.49 0.16 0.14

PenOH( 1:4)

PenOH( 1:4)

ratio = 1:l. Me

I CHr=C-COOMe

+ DVB

I

7

CCOMe -

%c::,:_,” b-

b-

0’

P

=CH2CHZOH

“~2

CONH

(CH 2)n NHCO-

R-

X

-

~~C~~CHZI,NHCO--R-P+(Ph)JX-

Pa-c a-

n=O

.R=CHZ,

X=CI

b-

n-2

,R=CHZ,

X=CI

c-

n-2

,Rs

CHz,X=Br w

Scheme 2. Aminolysis

of PMMA

resins [15].

IR spectroscopy. The percentage of reduction was also obtained quantitatively by further chemical modification through etherification

reactions and the conversion of the ester groups to hydroxymethyl groups, Schemes 2 and 3, were followed by nitrogen analysis and SOC12

PYr.

-

@&cHzCI

-

~xClii~-R-P+(PhlxX-

I

LIAIH,

QGHzoH

P (3

I CHzOCO-R-X XFJ-C a-R=CH2

.XzCI

b-

=(CH,),,,X=Br

C-

=\t//-CHz,X=Br

Scheme 3. Acylation

of reduced

PMMA

resins [16,17].

277

NH, NH.,

LIA H 4

i '

x~'-'b

MA/

'

"x~-:b

Scheme 4. Preparation of pyridine and quinoline derivatives of PMMA resins [17]. and acetylation, and halogen analysis. Another way of modification of special interest is the nucleophilic substitution of picolinvl- and quinaldinyl-lithium reagents on the carbonyls of the ester groups of P M M A resins, as shown in Scheme 4.

REACTIVITIES AGENTS

OF

POLYMERIC

RE-

The support, in addition to holding the reactive groups, plays an important role in determining the reactivity of reagent moieties [4 9]. A polymeric reagent may have a quite different reactivity from the conventional reagent due to the effects of several factors: steric hindrance by the polymer to the attachment of reactants to the reactive sites, incompatibility of the reactants and the polymer, or adsorption of the products onto the resin. Thus. more drastic reaction conditions may be required to reach satisfactory conversion. The design of a reactive functionalizcd polymer for use as a polymeric reagent must be planned bearing these important factors in mind, in order to maximize the advantages of the s,,'stcm while minimizing any potential problem. Appropriate choice of support structure and properties as well as reaction conditions can overcome the problems of slow reaction and lower yields of product than in homogeneous reactions. Although linear soluble polymers have several advantages arising from the homo-

geneity of the reactions, their use as polymeric reagents may give rise to a disadvantage in the form of their difficulty in separation from the reaction mixture. In turn, this limits the possible automation of the technique. In the use of a crosslinked functionalized polymer as a support for a reagent, the following properties are required in order to lead to an ideal effective reagent: (1) It should be totally insoluble in common solvents (a prerequisite for automation) to avoid losses of active groups and to facilitate easy handling, separation, and purification. (2) It should have a high degree of substitution with uniformly distributed reactive functional groups to avoid the use of large masses of polymer. (3) It should undergo straightforward reactions with the reactants, free of any side reactions or undesirable competing functionalities. (4) II should be capable of being recycled. through regeneration of the polymeric byproduct after use via a simple procedure. (5) In terms of physical form, the rcagcnt should consist of small spherical beads, necessary for column operation. There are a number of morphologies for crosslinked functionalized polymers. Those most frequently encountered, with enhanced properties as polymeric reagents, are microporous and macroporous resins of various crosslinking ratios. They are adequately penetrated by most reagents and retain sufficient mechani-

278 cal stability to provide ease of handling. They have found wide application in solid-phase reactions. (6) In terms of the support porosity, the polymeric reagent should have a porous structure to allow diffusion of reactants and solvents to the reactive sites; this depends on total surface area (internal and external), total pore volume, and average pore diameter. These physical parameters are closely interrelated, i.e., if a polymer has a large mean pore diameter then the number of pores is relatively small and the total interior surface area is restricted. The degree of crosslinking and the conditions employed during preparation of the resin determine the effective pore size. A high porosity allows good flow properties and does not hinder the penetration of substrates, leading to high activity of the polymeric reagent. (7) With regards to solvation behaviour, the support should have a backbone compatible with both solvents and reactants to favour the equivalence of all functional groups as in homogeneous systems. However, the factors that control the solvation of the bound reagents and transport of the reactants in the polymer can be modified, either by chemical reactions on the pendant groups or by alteration of the physical nature of the polymer. Good solvents diffuse quickly into crosslinked polymeric networks, resulting in swelling. The network becomes highly expanded and extremely porous. As the degree of crosslinking decreases, gel networks result which consist largely of solvent with only a small fraction of polymer backbone. The crosslinker ratio controls in an inversely proportional sense the degree of swelling, i.e., as the degree of crosslinking increases, the ability of the network to expand in a good solvent becomes reduced and penetration of reagents into the interior decreases. By using a copolymerization technique, the chemical structure of the polymer can be varied over a wide range in order to obtain a product with a

particular combination of properties. The hydrophilic or hydrophobic character of the polymer can be charged by variations in the nature and ratio of the comonomer units. Thus, solvent compatibility with the resin can be adjusted by proper selection of the comonomeric units in the polymer chain. (8) Concerning chain mobility the support should have a backbone which does not impose steric restrictions on the reactants circulating near the active sites. The mobility of the polymer chains and the substituents, i.e., free rotational motion, is a function of the degree of swelling, the crosslinking density, temperature, the flexibility of the chain segments, and the free volume generated by randomly distributed substituents. Crosslinkers restrict the long-range mobility of chain segments, thereby reducing substantially the collision frequency of substituents attached to different chain segments. The reactivity of a functional group may be low when it is directly attached to the backbone, as a result of the low mobility of the active sites and the steric hindrance imposed by neighbouring side groups or by the backbone. Thus, rate constants of reactions often decrease as the degree of substitution increases, which normally means that the overall reaction cannot go to completion. This problem of decreasing reactivity when using polymeric-reagents can be overcome by increasing the separation of the reactive site from the backbone via spacer groups. However, the polarity at the active site may be altered by the insertion of spacer groups, as may the distribution of active sites within the matrix, which can be adjusted by the comonomer units. (9) The support should have a stable linkage between the backbone and the reactive moiety to avoid leaching of the active reagents in use or recycle. (10) The support should have chemical stability. It should have a backbone which is inert towards the reactants, i.e., the structure of the backbone must be chemically stable

"Y~9

_1

APPLICATIONS AGENTS

and not susceptible to degradative scission by most chemical reagents under ordinary conditions. In this respect condensation polymers are of less use as supports for reagents. The support should also have good mechanical and thermal stabilities under reaction conditions. These stabilities are generally determined by the nature of the polymer and the extent of crosslinking. Increased physical stability can be achieved with increased crosslinking, but there always exists a balance between the required mechanical properties and the porosity of the network. (11) Surface impurities on the polymer beads have a great influence on the apparent lack of reactivity of a functionalized polymer. The reactivity may also be decreased by interfering functionalities introduced during preparation or chemical modification of the reagent. Furthermore, the reaction rate of the polymeric reagent depends on the concentration of the reactants, the nature of the solvent. the temperature of reaction, and the stirring rate.

+

~._P,~,~:,

POLYMERIC

RE-

Since the development of the concept of performing chemical reactions on solid phases in heterogeneous media, the application of chemical reagents covalently attached to functionalized polymers has found widespread use in solid-phase synthesis.

Polymeric Wittig reagents Many useful syntheses using polymeric Wittig reagents have been studied. The attachment of a phosphine moiety to a polymeric support has made it possible to overcome the main disadvantages accompanying conventional Wittig reactions, i.e., the difficulty of separating the product from triphenylphosphine oxide and the high cost of the reagent. For example, polystyryldiphenylmethoxymethyl- and methyhhiomethylphosphonium chlorides have been prepared by treatment of the polymeric phosphine reagent with methyl chloromethyl ether or thioether and used for conversion of carbonyl corn-

CI3SIH

R'--C~C--Z--Me

OF

C'CH---Z

://~'-- P . P h , 2 ~

~

XVlII

÷--CH:,--Z ~Vll

a-

Z =O

--Me

.... M e

C'-

[ Ph)p

8 9 5 °/o D S . 2 4 2

mmol

Pig

b - Z = 2 0 8 mr~'ol S / g

Y i e l d ,a/o

Z

~ I

R II

0

Ph

H

85

0

P~

Ph

92

0

-- ( C H 2 ) 4 -

0

- (CHp) 5 -

89

95

S

Ph

H

S

Ph

Ph

86 79

S

Ph

Me

81

Scheme 5. Preparation of vinyl ethers and thioethers h~' polymericWittig reagents XVlla,b [1O].

280

)~VlH

R = Me

93 %

R= Et

87%

-X'TX"

(Ph).

"Elk"

(ph} 2

Scheme 6. Preparation of vinyl ethers by polymeric phosphorane reagent [19].

native transformations. In addition to the relatively high yields of the products, the active reagent can be regenerated for reuse in further applications.

p o u n d s to substituted vinylethers and thioethers [19], as shown in Scheme 5. In addition, a polymeric phosphorane has been used to convert formate esters to vinyl ether derivatives [19], as illustrated in Scheme 6. The usefulness of these reagents arises from the simple work-up, eliminating separation problems, and from the ability to utilize the enol-ether intermediates with a protected aldehyde group as starting substances for alter-

Polymeric dehydrating reagents Polymeric phosphine reagents have also been used for the preparation of poly(styryldiphenylphosphine dibromide) as a mild and

Ph

J ~

~

Z

ph

Ph

II ,,--..--c--..--~.~

~~-.- - I~~

O

r ~-

li @-~(~1~.

-~-~'~"

~--.=~=N--~'

Br? Z

R

O

Ph

Ph

R'

Yield.% 92

S

Ph

Ph

88

O

Ph

CsH..

85

O

C6H..

CoH..

76

Scheme 7. Preparation of carbodiimides from urea and thiourea derivatives [20]. R

O

I II R--CH--C--NH--R"

Ph +

,--, I÷ (PS~--P--B -

O r Br-

~

2Et3N

I Ph

[I

;~-.~ (U~/~p(Ph)

R 2 *

[

R--C:C:N--R'

"

R'

Yield,*/,

P~

Ph

Me

Ph

90 70

Ph

n - - Bu

89

Scheme 8. Preparation of keteneimines from N-substituted amides containing a-hydrogen [20].

_,Xl

0

Ph

II *

PS~-P

Br

O

I*

~ "

Ph---C--NH--Ph

E[ ' N --Br

B¢-

--'-

"

~I -

I

'PS~P[Ph)?

+

Ph--C~----N-Iph

[

88 %

Ph

Scheme 9. Preparation of imidoyl bromide from amides containing no a-h?,Idrogen [201.

efficient reagent for the synthesis of some compounds which are sensitive to water and high distillation temperatures. Some examples are carbodiimides from N,N'-disubstituted urea and thiourea [20], Scheme 7, ketenimines from N,N'-disubstituted amides containing ~x-hydrogen [20], Scheme 8, and imidoyl bromide from N-substituted amides containing no ~x-hydrogen [20], Scheme 9.

phosphonium salts have not previously been used as stoichiometric reagents in spite of their superior chemical and thermal stabilities relative to the corresponding ammonium salts. In general, they have only been used ax phase-transfer catalysts in similar organic reactions. Hence, polymeric phosphonium salts have been prepared and used for supporting bromine to be used in stoichiometric quantitie,,, for direct bromination of alkenes and carbonvl compounds under miM conditions [21], as shown m Scheme 10. in addition to the simplicitv of the method and the cxcellcnt \ields of the brommatcd products a~, a result of using excess polymeric reagent, the resull-

Polymeric halo,genatm~¢ reaj¢ents Various functionalized polymers have been used as halogen carriers in the halogenation of organic substrates. However. polymeric R--CH

Br XXll

*

P(PhJ. i

a-

R= Ph

b-

~ ='PS:

-

~IC~

P {PX)~Br XXII I a b ]

! ° XX'J

a b

Bf

-Ph

.COCH

I

--~"

'

-CH~CM

)

Ph

--:

t ....

r'~

13-

I ...... B "

Re~ent

XXl',/ a

Substrate

~

~X,'~ a

0 ~~

0 -~-x "

~.j

.~

XXVa

CP~CH

CHO

CH

Co~d;t io~s

Y i e id

%oi v

Te~p

.B -

THe-

~ t

Br

(-¢ I.:

i t

.," F. (.;

r t

40rn'r:

90

r t

4b~q

~C

~ t

4C m'n

7~

-~'"

; '~

~S

ref

' h

92

" t

3t) me

O,'t"

r t

4'. m q

85 °

PhCOCP'

XXI'¢ b

Br

Reaction

Pr o d i j ( t

PhCOCP'

"'~'"

C~t - - ( . h O

T,me 1h

7(:

3 f~ "',


I XXIV ~ XXl'v' a

CH[ [COOEt

):

C~:C00Et):

gt()H

I t3r XXIV b XXIVa

Ph--C~CH:

P~(-H(_H*~

C~

.'.'

I Br XXIV b • Obtained

wit ~ regemerated

-esl~

Scllcme 10. Brominaticm of carhon\'l compoun&, and alken¢~, ,aith polymeric brominating reagent XXIV [211.

282 used as stoichiometric reagents to increase the activity of these anions in nucleophilic reactions. Carboxylic acid esters have been prepared in both nonpolar and polar solvents with excellent yields [22], as shown in Scheme 11. Hydrophilic and hydrophobic solvents are equally effective, indicating that the microenvironment of the reaction site in the resin is almost independent of the nature of the

ing polymeric by-product can be simply regenerated after use to give the polymeric brominating reagent without loss of activity.

Polymer-bound nucleophiles As a result of the advantages of using phosphonium salts, polymeric reagents with various bound anions have been prepared and

R

R'--X

soIv

temp

Ph

Me--I

BZ

rt.

BZ Bz CH2Cl2 THF EtOH N20 BZ BZ MeOH Bz

60"

O2N ~ C ~

=--Pr--I Me--I

i--

PhCH~CH--

Pr--I

PhCH?CJ Me--I PhCH2CI

rt

r t, rt r.t. rt 60" ref rt 60 =

tln~h Yield,%

5 12

95 73 86 88 90 81" 85 82 90" 83 80

5

5 4 6 12 10 6 15 8

"Obtained with regener@ted resin

Scheme 11. Preparation of carboxylic acid esters from alkyl halides and polymeric reagents XXV [22]. ~ S ~ - C H 2 P (Ph)3 O - - A C

R'--X

XXV]

Ar--O

~

~

R'--X O

Me--I

. Ar --

Y

ONa

Product* M e .

solv OH

O? N - - - ~ - O

O2 N - - ~

~

~ O M e

O

~S--~C,2P ,ph)3X- ÷ R ' - - O - - A r

tlme,h

Bz EtOH

12 12

50 60

OMe EtOH

12

50

EtOH

20

57

Me

IJ 70 43:

.~O H

~

Yield,°/~

~OCH2Ph O

PhCH2CI

BZ

~ o HCH2Ph

20

88.

12,:90 ~

• Reactions at room temperature ÷Obt~lr~ed with reger~rated resin

Scheme 12. Preparation of ethers from alkyl halides and polymeric reagents XXVI [22].

283

R'--X

p-<£'~---CHzP'(Ph)3 - O 2 S - - p h

*

~AVH

=

~

PhSO

( P s ' ~ CH2P*(Ph)q X- *

~Na

R'--O~S--Ph

Y

R e a ¢ t iorl

R'--

X

t l m e h ÷ Yleld?/o

Me--I

2

80

Et

2

60

3

50

--I

,--- P---

I

PhCH; C'

3

75

EtOCO--CHjCI

3

55

÷

berzene

,n r e ~ u x , n g

Scheme 13. Preparation of sulphones from alkvl halides and polymeric reagent XXVll [22].

medium. Runs with catalytic amounts of the polymeric salt did not give satisfactory results in esterification reactions, showing that the polymeric reagent probably increases the nucleophilicity of the carboxylate anions. C/O-Alkylated phenols have been synthesized bv the reaction of polymer-bound phenoxide anions with alkyl halides [22], as shown in Scheme 12. The results of these reactions show that O-alkylation products are predominant. except for the reaction of methyl iodide

~

--X

:PS~---CH;P

+

÷

Ph)

Y

-

with phenoxide ion in which C-alkylation of phenol is favoured. Thus, the polymeric reagents seem to increase the activities of the anions in a similar manner to low molecular catalysts. The reactions of polymer-supported sulfinate anion with alkyl halides in benzene gave the sulfones in good yields [22]. as shown in Scheme 13. The effectiveness of the polymeric salts as anion-activating reagents has been studied in numerous nucleophilic substitution reactions, f-~

--

--

'PS--CH2P

÷

',Ph)jX

-

+ R'--Y

XXV:; ~

K

Y

Y

R'--X

R "--Y

SCN

P~CH ?('L

PhCH2SCN

temp

solv

B;'

t,me

Yield

3

56

ref

+ PhC 14;)NC:S NC 2

P~CHp~r

PhCN2SCN

CHpC' 2

ref

3

93

PmCH2Bq--gu--£r

P~CH2NO 2

Bz

r t

24

8~

n - - B u - - - NO 2

8Z

rt

24

21

CIC~2COOEt

OzN - - CH2COOEt

BZ

rt

24

33

Scheme 14. Preparalion of thiocyanates and nitroalkanes from alkvl halides and polymeric reagents XXYlll [231. O

li

R--C--R"

OH +

"F'S)~ CHeP+(Ph)? BH 4

I

R--CH---R"

-- ~

XXlX RC OR"

Product ~"

temp t

me, h Yield,%

PhCOMe

PhCH (OH) Me

tel

3

70 70

PhCODh

PhCH(OH) Ph

ref

3

90

PhCHC

PhCH?O~-

ret

3

r t

48

98 I(}(]

+react.ons ,n benzene

Scheme 15. Reduction of carbonvl compounds with polymeric reducing reagent XXIX [231.

284

such as the preparation of alkyl thiocyanates and nitroalkanes [23], as shown in Scheme 14. In addition, a polymeric reducing reagent has been prepared and used in the reduction of aldehydes and ketones in non-polar solvents [23], Scheme 15.

REFERENCES 1 A. Akelah. Biological applications of functionalized polymers. A review, J. Chem. Technol. Biotechnol., 34-A (1984) 263-286. 2 A. Akelah and A. Selim, Applications of functionalized polymers for controlled release formulations of agrochemicals and related biocides, Chim. Ind., 69 (1987) 62-67. 3 A. Akelah, Technological applications of functionalized polymer, J. Mater. Sci., 21 (1986) 2977-3001. 4 P. Hodge and D.C. Sherrington, Polymer-Supported reactions in Organic Synthesis, Wiley, London, 1980. 5 N.K. Mathur. C.K. Narang and R.E. Williams, Polymers as Aids in Organic Chemistry, Academic Press, New York, NY. 1980. 6 M.A. Kraus and A. Patchornik. Polymeric reagents, J. Polym. Sci., Macromol. Rev., 15 (1980) 55-106. 7 J.M.J. Fr6chet, Synthesis and applications of organic polymers as supports and protecting groups, Tetrahedron, 37 (1981) 663-683. 8 W.T. Ford, Polymeric Reagents and Catalysts, ACS Symposium Series, No. 308, American Chemical Society, Washington, DC, 1986. 9 A. Akelah and D.C. Sherrington, Recent development in the application of functionalized polymers in organic synthesis, Polymer, 24 (1983) 1369-1386. 10 J.M.J. Fr6chet and M.J. Farrall, Functionalization of crosslinked polystyrene resins by chemical modification: a review, in: S.S. Lablana (Ed.), Chemistry and Properties of Crosslinked Polymers, Academic Press, New York, NY, 1977, pp. 59-83. 11 A. Akelah, Preparation, properties and characterization of functionalized polymers, J. Macromol. Sci., Rev. Macromol. Chem. Phys., C-27 (1987) in press. 12 A. Akelah, Use of functionalized silica in catalysis and organic synthesis, Br. Polym. J.. 13 (1981) 107-110.

13 A. Akelah and D.C. Sherrington, Synthesis of some vinyl derivatives of cellulose and their grafting copolymerization with styrene. J. Appl. Polym. Sci.. 26 (1981) 3377-3384. 14 A. Akelah and D.C. Sherrington, Preparation and synthetic application of cellulose-supported phase transfer catalysts, Eur. Polym. J., 18 (1982) 301-305. 15 A. Akelah, M. Hassanein, A. Selim and E.R. Kenawy, Synthesis and chemical modification of poly(methyl methacrylate) resins, Eur. Polym. J., 22 (1986) 983985. 16 A. Akelah, M. Hassanein, M. EI-Sakran and E.R. Kenawy, Phase transfer catalytic behaviour of modified poly(methacrylate) resins containing phosphonium salt groups, Polym. Prepr. Amer. Chem. Soc. Div. Polym. Chem., 27 (1) (1986) 468--469. 17 A. Akelah and A. Selim, Chemical modification of poly(methyl methacrylate) resins with pyridine derivatives, submitted for publication. 18 A. Akelah, S.B. Kingston and D.C. Sherrington, Rigid macroreticular poly(N,N-dimethyl-p-vinylbenzamide) based supports for use in solid phase synthesis, Polymer, 24 (1983) 281-284. 19 A. Akelah, Preparation and application of functional polymers. Preparation of vinyl ethers and thioethers using polymer-supported phosphonium salts, Eur. Polym. J., 18 (1982) 559-561. 20 A. Akelah and M. EI-Borai. Preparation and application of functional polymers. Preparation of carbodiimides, ketenimines and imidoyl bromides using a polystyryldiphenylphosphine dibromide, Polymer, 21 (1980) 255-257. 21 A. Akelah, M. Hassanein and F. Abdel-Galil, preparation of poly(vinylbenzyltriphenylphosphonium perbromide) and its application in the bromination of organic compounds, Eur_Polym. J., 20 (1984) 221-223. 22 M. Hassanein, A. Akelah and F. AndeI-Galil, Synthesis of poly(vinylbenzyltriphenylphosphonium-bound nucleophilic) reagents and their applications for anionic activation in nucleophilic substitutions, Eur. Polym. J., 21 (1985) 475-478. 23 A. Akelah and F. Abdel-Galil, Chemical modification of poly(vinylbenzyhriphenylphosphonium salts) and their applications as reagents in organic synthesis, 10th International Conference on Phosphorus Chemistry, Bonn, F.R.G., 31 August-6 September 1986.