polystyrene-supported cr(vi) reagents: a new class of recyclable oxidising reagents

REACTIVE &

FUNCTIONAL POLYMERS

ELSEVIER Reactive & Functional Polymers 34 (1997) 19-25

Polystyrene-supported Cr(V1) reagents: a new class of recyclable oxidising reagents

Shiney Abraham, P.K. Rajan, K. Sreekumar *

Department of Chemistry, University of Kerala, Kariavattom, Trivandrum, 695 581 Kerala, India

Received 16 October 1996; accepted 14 February 1997

Abstract

Polystyrene-supported isoxazolinium chromate and chlorochromate resins were prepared and developed as ~ recyclable reagents for oxidation of alcohols to carbonyl compounds. Divinylbenzene (DVB) and ethylene glycoldim thacrylate (EGDMA) crosslinked polystyrene resins (2%) were used as the macromolecular supports. These insoluble Cr( J I) reagents were found to be selective in carrying out oxidation reactions. EGDMA-crosslinked polystyrene-supported reagents showed higher reactivity in terms of functional group capacity, reaction time and product yield. The spent reagent can be recycled and reused without appreciable loss of reactivity.

Keywords: Polystyrene-supported Cr(VI) reagents; Macromolecular supports; Polymeric reagents

1. Introduction

Polymeric reagents have been developed for use in functional group transformations [ 141 and in peptide synthesis [5,6]. In all of these appli- cations, advantage is taken of the insolubility of the polymeric reagent and of its byproduct which allows for easy removal of any excess reagent or spent material from the desired product.

Many chromium(V1) oxidising reagents in- cluding neutral [7] and ionic [8] complexes with nitrogen heterocycles are well known. Even though these oxidising reagents have many ad- vantages, they all suffer from several drawbacks: (a) tedious recovery of the oxidation product from the precipitated or colloidal Cr(II1) and/or Cr(V1) oxides, (b) nitrogen heterocyclic com-

pound used as a coreagent is never recovered, and (c) chromium is carcinogenic at any stage of its oxidation [9]. But when these’ reagents were anchored to an insoluble polymer support, it was expected to eliminate mubh of the difficulties encountered with these lob-molec- ular-weight reagents. The present aper de- scribes the preparation of DVB- and $ GDMA- crosslinked polystyrene-supported isoxazolinium chromate and chlorochromate reagents and their application as oxidising reagent i for alcohols.

2. Experimental

* Corresponding author.

DVB- and EGDMA-crosslinked polystyrene resins were prepared by suspension polymerisa- tion method. Chloromethylation of polystyrene [lo] and subsequent oxidation [12] and esteri-

1381-5148/97/$17.00 0 1997 Elsevier Science B.V. All rights reserved. PIZ S1381-5148(97)00020-5

20 S. Abraham et al. /Reactive & Functional Polymers 34 (1997) 19-25

fication [ 131 reactions were done according to literature procedures.

2. I. Preparation of polystyrene bound 1,3 diketones (6a, 6b)

Carbethoxy polystyrene resin (10 g), preswollen in THF (20 ml), was refluxed with acetophenone (15 ml) in the presence of sodium ethoxide (5 g) for 12 h. The mixture was cooled to room temperature and dil. H2SO4 (20 ml) was added and stirred for 30 minutes. It was then filtered at the pump, washed with water, ethanol and acetone (20 ml x 3 times each), dried in vacuum. Yield: 10.99 g for 6a and 11.2 g for 6b.

2.2. Preparation of polymeric isoxazole resin (7a, 7W

Polymeric /I-diketo resin (10 g) was heated to reflux with hydroxylamine hydrochloride (4 g) in the presence of pyridine (10 ml) for 12 h. The mixture was cooled to room temperature and water (10 ml) was added, filtered at the pump, washed with water, acetonitrile, ethanol and acetone (20 ml x 3 times each), dried. Yield: 9.8 g for 7a and 9.67 g for 7b.

2.3. Quaternisation of polymeric isoxazole resin @a, SW

Polymeric isoxazole resin (10 g), preswollen in acetonitrile (20 ml), was reacted with methyl iodide (10 ml) at the refluxing temperature for 10 h. After the reaction, the mixture was filtered, washed with water, ethanol and acetone (20 ml x 3 times each), dried and weighed. Yield: 10.5 g for 8a and 10.6 g for Sb.

2.4. Preparation of polystyrene-supported chromate resin (9a, 9b)

Quaternised polymeric isoxazole (10 g), preswollen in acetonitrile (10 ml), was stirred at 30°C with CrG3 (3 g) dissolved in water (10 ml) for a period of 10 h. The resin was filtered and

washed with distilled water until the filtrate was clear. It was then washed with acetone, dried and weighed. Yield: 9.82 g for 9a and 9.80 g for 9b.

2.5. Preparation of polystyrene-supported chlorochromate resin (lOa, lob)

Polymeric isoxazole resin (10 g), preswollen in acetonitrile (20 ml), was suspended in an acetonitrile-water mixture (1 : 1 v/v), CrG3 (4 g) and concentrated HCl (10 ml) were added. The mixture was stirred at room temperature for 10 h and filtered, the resin was washed with distilled water until the filtrate was clear. Finally it was washed with acetone (10 ml) and dried. Yield: 10.8 g for 10a and 11 g for lob.

2.4. Oxidation of alcohols

The alcohol (1 mmol) was dissolved in chloroform (10 ml). A two-fold molar excess of the polymeric reagent was added and the reaction mixture was stirred. The reaction was followed by thin layer chromatography. After the completion of the reaction, resin was filtered and washed with chloroform. The combined filtrate and washing on evaporation of the solvent af- forded the corresponding car-bony1 compounds.

3. Results and discussion

3.1. Synthesis ofpolystyrene-bound chromate and chlorochromate resins

2% DVB-crosslinked polystyrene (la) and EGDMA-crosslinked polystyrene (lb) were used as the macromolecular supports. Synthesis of polystyrene-bound Cr(V1) reagents involved a se- ries of polymer-analogous reactions. The reaction sequence is shown in Scheme 1.

A chloromethyl group was introduced on to the polystyrene resin beads (la, lb) by Friedel Crafts reaction with chloromethyl methyl ether using a Lewis acid catalyst such as SnCb [lo]. Chloromethyl methyl ether, which is carcinogenic, can be replaced by less carcinogenic long-

S. Abraham et al. /Reactive & Functional Polymers 34 (1997) 19-25 21

HzCOOGHs

CGH5COCH~ CIHSONa

C2H50H *

H’ CH2COOH

4a,4b

.

Scheme 1. Preparation of polystyrene-supported isoxazolinium chromate and chlorochromate resin.

chain chloromethyl alkyl ethers [ 111. The sub- stitution of chloromethyl group was evidenced by the strong absorption band in IR spectrum around 690 cm-’ (C-Cl str). The chlorine capacity was determined using modified Volhard’s method by digesting the resin with pyridine followed by determination of the displaced chlorine as silver chloride. The capacities were found to be 4.2 and 4.4 meq/g for 2a and 2b, respectively. Reaction of the chloromethyl polystyrene, (2a, 2b) with KCN in DMF-water mixture gave cyanomethyl polystyrene [ 121 (3a, 3b) which was characterised by IR absorption band at 2240 cm-’ (C=N str). The cyanomethyl polystyrene on hydrolysis with CH$OOH-HzS04 mixture

resulted in polystyrene carboxylic acid resin [ 131 (4a, 4b), formation of which was supdotted by the IR absorption bands at 1690 cm+’ (C=O str) and 1420 cm-’ (C-O str). The acid group capacity determined by volumetric m+od was found to be 3.5 and 3.7 meq/g for resi s 4a and

“, 4b, respectively. The acid-functionalise resin on treatment with absolute ethanol in then presence of a small amount of H2SO4 afforde d the formation of carbethoxy polystyrene [ 141~ (5a, 5b), characterised by absorption bands at 1700 cm-’ (C=O str) and 1240 cm-’ (C-O str) iin the IR spectrum. The ester group capacity *as determined by saponification method. The capacities were found to be 3.1 and 3.3 meq/g fok- resin 5a

22 S. Abraham et al, /Reactive & Functional Polymers 34 (1997) 19-25

and 5b, respectively. The carbethoxy polystyrene resin was converted to the ,&diketo resin (6a, 6b) by Claisen condensation with acetophenone and sodium ethoxide. This was evidenced by IR spectral values and elemental analysis. The j?-diketo resin was a tautomeric product as evidenced from the IR spectral values. The IR spectra showed enol absorption bands at 1560-1640 cm-’ which were assigned to C=O . . . H and C=C stretching vibrations characteristic of cyclic intramolec- ular hydrogen-bonded molecules. The absorption bands at 1680-1700 cm-’ were assigned to two C=O stretching vibrations of the keto form. The enol capacity determined by acety- lation method [ 151 was found to be 2.6 meq/g for DVB-crosslinked resin and 2.9 meq/g for EGDMA-crosslinked resin. The p-diketo resin was converted to the isoxazole-functionalised resin (7a, 7b) by reaction with hydroxylamine hydrochloride in pyridine. Absence of characteristic coloration with neutral FeCls indicated the nonformation of oxime. The oxime formation was prevented due to the predominance of the enol form over the keto form. The formation of polystyrene-bound isoxazole resin gave strong absorption bands at 1630 cm-’ (C=N str) and 1650 cm-’ (C=C str) in the IR spectrum. The capacity of I- incorporated in the resin was determined by treatment of the resin with AgN03 followed by determination of the displaced iodide as silver iodide. The capacities were 1.4 meq/g and 2.2 meq/g for resins Sa and 8b, respectively.

The isoxazolinium iodide resin was then converted to isoxazolinium chromate resin (9a, 9b) by reaction with 003 in CHsCN-Hz0 mixture. The resins showed strong IR bands at 940 cm -I, 890 cm-’ and 758 cm-l characteristic of chromate functional group. The isoxazolinium chlorochromate resin (lOa, lob) was prepared from isoxazole resin by reaction with 003 and concentrated HCl in CHsCN-Hz0 mixture. The formation of chlorochromate function in the resin was supported by the observation of strong bands at 3050 cm-’ (N-H str) and 958 cm-‘, 835 cm-’ and 755 cm- l (ClCrG3- str) in the IR spectrum. The chromate and chlorochromate functions were

estimated iodometrically and had capacities of 1.2 meq/g and 1.3 meq/g, respectively.

3.2. Oxidation reaction using polystyrene-bound Cr( VZ) reagents

The polystyrene-bound isoxazolinium chromate and chlorochromate resins were observed to be capable of oxidising primary and secondary alcohols to the corresponding carbonyl compounds. The oxidation conditions involve stirring of the alcohol with a two-fold molar excess of the resin in solvents like chloroform at 30°C. The work up of the reaction mixture involved filtra- tion of the spent residue, washing and removal of the solvent from the combined filtrate and washing to afford the oxidised product. The different alcohols which were oxidised using this procedure, the yield and conditions of oxidation are presented in Table 1.

It is seen that the time required for completion of the reaction is slightly reduced in the case of EGDMA-crosslinked Cr(V1) reagents when compared to DVB-crosslinked reagents. The enhanced reactivity of the former can be attributed to the flexibility of the system and also to the increased compatibility with reagents and solvents. A reasonable explanation to the increased reactivity of EGDMA-crosslinked support is the possibility of the diester of EGDMA taking part in a sort of in- tramolecular reaction and as a result of which the degree of crosslinking is considerably low. This leads to better diffusion profiles for the low molec- ular weight reagents, substrates and solvents [ 161.

When compared to isoxazolinium chromate resins, chlorochromate resin showed a slight increase in reactivity which can be explained by the less basic nature of the anion bound to chromium in chlorochromate than that bound to chromium in chromate resin [ 171.

3.3. Eflect of reaction conditions on the extent of oxidation reaction

The oxidation reaction using polystyrene-supported Cr(V1) reagents were found to be affected


Table 1 Oxidation of alcohols using DVB- and EGDMA-crosslinked polystyrene-supported chromate and chlorochromate resin

Alcohol a Timeb (h) Product c Isolated yield (%) me/be W)

9a 9b 10a lob 9a 9b 10a lob

Benzoin 31 30 29 28 Benzyl 83 82 85 84 95 Benzhydrol 36 35 34 32 Benzophenone 78 80 83 84 49 Benzyl alcohol 40 39 38 37 Benzaldehyde 75 78 81 80 (179) n-Butanol 38 37 36 35 n-Butyraldehyde 75 75 80 80 (75) Cholesterol 46 45 41 42 A5-Cholestenone 78 77 81 82 85 p-Nitro benzyl alcohol 43 31 41 29 p-Nitro benzaldehyde 76 80 80 81 58 cy-Phenyl ethanol 36 41 34 40 Acetophenone 78 75 82 81 ~(205) p-Methyl benzyl alcohol 40 38 38 36 p-Methyl benzaldehyde 80 80 80 83 ‘(202) p-Methoxy a-phenyl ethanol 37 36 35 35 p-Methoxy acetophenone 82 81 85 86 39 cis- 1,2Cyclohexane diol 33 36 30 34 2-Hydroxy cyclohexanone 81 85 83 88 105

a Alcohol-to-resin ratio, 1 : 2; solvent, chloroform; temperature, 30°C. b Includes time for preswelling also. c Characterised by comparison with authentic samples (IR, mp/bp).

by the nature of the solvent, temperature, effective molar concentration of the reagent function and catalyst. It has been observed that only when there is an effective interaction between the reagent function, the substrate and the reaction medium, reaction takes place with reasonable extent of functional group conversion.

3.3.1. Effect of solvent In order to investigate the effect of the na-

ture of solvent on the reactivity of polystyrene- supported isoxazolinium Cr(V1) reagents, oxidation of benzoin was conducted using DVB- and EGDMA-crosslinked polystyrene-supported isoxazolinium chromate resins in different solvents of varying polarity. The studies reveal that THE is the most effective solvent. The time for maximum conversion using isoxazolinium chromate resin in various solvents are presented in Table 2.

The conversion rate was higher in acetonitrile and also in dichloromethane. The polystyrene support is hydrophobic in nature. But the introduction of chromate function on to this polystyrene matrix gave some polarity to the network. Thus, in this case the ability of hydrocarbon solvents in swelling this polymer matrix was found to be decreased and good results were obtained with slightly polar solvent like THE

Table 2 Details of oxidation of benzoin in various solvents using isoxazolinium chromate resin

Solvent Time for maximum conversion (h) a

9a 9b

Dichloromethane 30 28 Tetrahydrofuran 27 26 Chloroform 31 30 Dioxane 34 33 Benzene 32 31 Acetonitrile 28 27 Cyclohexane 35 32

a Resin-to-alcohol ratio, 2 : 1; temperature, 30°C.

3.3.2. Infuence of temperature Influence of temperature on the extent of ox-

idation reaction was studied by carryin 1

out the reaction at different temperatures varyng from 20°C to 60°C. The procedure was to stir benzoin dissolved in chloroform with a two-fold molar excess of the reagent at the specified ltempera- ture. The time for maximum conversion using DVB- and EGDMA-crosslinked isoxazolinium chromate resin at temperatures 20,30,40,50 and 60°C are given in Table 3.

As the temperature was increased, the time for maximum conversion was decreased gradually. The higher reactivity of the oxidising magent at higher temperature may be due to the a tainment of the required activation energy by the m olecules.

24 S. Abraham et al. /Reactive & Functional Polymers 34 (1997) 19-25

Table 3 Table 5 Effect of temperature on oxidation of benzoin using isoxazolinium chromate resin

Effect of catalyst on the oxidation efficiency of DVB- and EGDMA-crosslinked polystyrene-supported isoxazolinium chromate resin

Temperature (“C) Time for maximum conversion (h) a

9a 9b

20 40 37 30 31 30 40 26 23 50 24 20 60 20 17

a Alcohol-to-resin ratio, 1 : 2; solvent, chloroform.

Catalyst Time for maximum conversion (h) a

9a 9b

2 N T&S04 24 22 Acetic acid 21 25 Water 30 27 No catalyst 31 30

a Alcohol, benzoin; alcohol-to-resin ratio, 1: 2; temperature, 30°C.

Table 4 Dependence of extent of reaction on the relative concentration of the reagent

Molar ratio % of benzil after 10 ha

9a 9b

1:l 10 12 I:2 15 18 1:3 19 23 1:4 21 21 1:5 29 32

a Solvent, chloroform; temperature, 30°C; alcohol, benzoin.

3.3.3. Concentration of the reagentfunction

action using isoxazolinium chromate resins. The oxidation of benzoin was selected as a model reaction to study this effect. The reactions were carried out with 2 N H2SO4, acetic acid, Hz0 and without any catalyst. The presence of catalyst was found to enhance the speed of the oxidation reaction. Thus it was observed that only 24 h was needed for complete conversion of benzoin using DVB- crosslinked polystyrene-supported isoxazolinium chromate, when H2SO4 was used as the catalyst, while 3 1 h was needed when there was no catalyst. The results are presented in Table 5.

Oxidation reaction using polystyrene-supported isoxazolinium chromate reagent was found to be dependent on the concentration of the reagent function. In order to study the dependence of the reactivity of isoxazolinium chromate reagent on the effective concentration, the oxidation reaction of benzoin was conducted at different reagent to substrate ratios such as 1 : 1, 2:1,3:1,4:1and5:1.Thepercentageofbenzil obtained after a definite time interval (10 h) was determined spectrophotometrically. The results are given in Table 4.

3.4. Regeneration of the spent resin

With an increase in resin-to-alcohol ratio, there was a corresponding increase in the percentage of benzil formed. It was found that the percentage of benzil formed was almost tripled when the resin-to-alcohol ratio was changed from 1 : 1 to 5 : 1.

3.3.4. Efect of catalyst The presence of small amounts of acid (H2SO4

or CHsCOOH) enhances the rate of oxidation re-

A major consideration in the use of polymer- supported isoxazolinium Cr(V1) reagent was the possibility of recycling and reuse of the spent reagent. The polymeric byproduct obtained after the oxidation reaction was found to have chromium in the +3 oxidation state along with some unreacted Cr(V1) species. The partially spent reagent could get rid of the chromium species by reacting with alcoholic KOH solution. All the chromium species was removed from the resin as potassium salt. The regenerated resin obtained from chromate resin was in the quaternised form which on reaction with CrOs in water- acetonitrile mixture resulted in the formation of isoxazolinium chromate resin, while the regenerated resin obtained from chlorochromate resin was the isoxazole resin which on reaction with CrOs and concentrated HCl in water-acetonitrile


Table 6 Regeneration of the DVB- and EGDMA-crosslinked isoxazolinium chromate and chlorochromate resin

No. of cycles Capacity (meq/g) Isolated yield (%) a

9a 9b 10a lob 9a 9b 10a lob

1 1.2 1.3 1.3 1.4 83 82 85 84 2 1.1 1.2 1.2 1.3 81 80 83 82 3 1.0 1.1 1.2 1.2 79 78 83 80 4 0.8 1.0 1.1 1.2 76 76 81 80 5 0.8 1.0 1.1 1.1 76 76 81 78

a Alcohol, benzoin; solvent, chloroform; resin-to-alcohol ratio, 2 : 1; yield determined spectrophotometrically.

medium resulted in the formation of isoxazolinium chlorochromate resin as in the original case. The regenerated resins were found to be of almost identical reactivity as that of the original resin. The details are given in Table 6.

Acknowledgements

The authors thank the U.G.C. New Delhi for the award of a Senior Research Fellowship to Shiney Abraham.

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polystyrene-supported cr(vi) reagents: a new class of recyclable oxidising reagents

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