Indian Journal of Chemistry
Vol. 45B, April 2006, p p. 943-950
Epoxidation and oxidation reactions using divinyl benzene
crosslinked polystyrene supported t-butyl hydroperoxide
M S Sheela & K Sreekumar*
Department of Polymer Chemistry, Mannaniya College of Arts and Science, Pangode
Kallara (Via) Thiruvananthapuram 695 605, Kerala, India
*Department of Applied Chemistry, Cochin University of Science and Technology
CUSAT Campus, Kochi 682 022, Kerala, India
E-mail: [email protected]
Received 4 March 2004; accepted (revised) 20 July 2005
Divinyl benzene (DVB) crosslinked polystyrene supported t-butyl hydroperoxide resin has been prepared and employed
in the epoxidation of olefins and oxidation of alcohols. The reagent is found to be efficient as the low molecular weight tbutyl hydroperoxide. Presence of catalyst enhanced the reaction efficiency remarkably. Influence of various reaction parameters
such as solvent, temperature and molar excess of the reagent on the reactivity of the polymeric reagent is also being investigated.
Keywords : Polystyrene supported reagent, epoxidation, oxidation reaction, heterogeneous reaction, polymer analogous reaction
IPC: Int.Cl7 C07 D
Over the last one decade, combinatorial chemistry has
revolutionized the pharmaceutical industry’s discovery
of new drug like compounds and permanently altered
the drug-development processes1,2. The application of
solid supports for synthesizing compound libraries for
biological screening purposes by combinatorial and
parallel techniques has achieved considerable interest
am ong scientists fr om a cad emic an d indu strial
organisations3-5. Solid phase synthesis continues to
hold a dominant position in combinatorial synthesis as
more chemistries are developed in this field 6-8. A wide
range of polymeric reagents have been developed since
the introduction of Merrifield resin 9-11. Polystyrene
bound t-butyl hydroperoxide has been developed as a
solid phase organic reagent for the conversion of alkyl
and aryl halides to hydroxy compounds through a
Grignard type reaction 12. The present work describes
the epoxidation of olefins and oxidation of alcohols
using DVB crosslinked polystyrene supported t-butyl
hydroperoxide reagent.
Results and Discussion
P reparation and Characterization of the Reagent .
2% Divinyl benzene (DVB) crosslinked polystyrene
resin 1 was functionalized to incorporate t-butyl hydroperoxide (TBHP) group by a three step polymer analogous reaction 12 as shown in Scheme I . The steps include (1) Friedel–Crafts alkylation of polystyrene with
bromoacetone, (2) Grignard reaction of 2-oxopropyl
polystyrene and (3) conversion of t-butyl alcohol to
TBHP.
Friedel-C rafts alkylation of po lystyrene w ith
bromoacetone yielded 79% of oxopropyl resin 2 which
showed intense absorption band at 1720 cm -1 in the
infrared region. The resin 2 was converted to t-butyl
alcohol resin 3 by Grignard reaction using methyl
io dide . Th e IR a bs or ptio n ba nd a t 1720 c m - 1
disappeared indicating the conversion of the keto group.
The t-butyl hydroperoxide (TBHP) resin 4 obtained
from the t-butyl alcohol showed strong IR absorption
bands at 876, 1520 (C = C arom str) and 3310 (O-H
str) cm -1.
Epoxidation of Olefins . The polymeric TBHP was
found to epoxidise olefins in reasonable yields as per
S c he m e II . Details of catalyzed and uncatalyzed
epoxidation of various olefins using the polymeric
TBHP are presented in Ta ble I . Attempts were made
initially to follow the reported procedure for alkaline
944
INDIAN J. CHEM., SEC B, APRIL 2006
+
CH3COCH2Br
CH2COCH3
(2)
anhydrous AlCl3
(1)
THF
CH3I/Mg
CH3
CH3
(1) 70% H2SO4, 100C
CH2
C
CH2
OOH
(2) H2O2
C
OH
CH3
CH3
(3)
(4)
Scheme I— Functionalisation of polystyrene resin
CH3
C
+
C
CH2
C
OOH
Substrate to resin, 1:2,
dioxan, 70°C
CH3
CH3
O
C
C
+
CH2
C
OH
CH3
Scheme II— Epoxidation of olefins using
polymeric t-butyl hydroperoxide reagent
e po xida tion 1 3 . Ad d itio n o f a lk ali ef f e cte d n o
appreciable variation in either the yield or reaction
time as observed in the uncatalysed reaction. Hence,
the epoxidation reactions were performed in the
absence of alkali.
Even though, uncatalyzed epoxidation of olefins is
observed only rarely in the literature, the polymeric
TBHP reported here was found to epoxidise a number
of olefins even in the absence of catalysts yielding
products ranging from 40 to 55%. When the substrate
contains an -OH group in addition to the double bond,
the polymeric TBHP attacked both the groups. This
was observed with cholesterol, in which the major
product was that obtained by the oxidation of –OH
group. When 68% of the oxid ized produ ct was
produced, the yield of epoxide was only 10%. In
addition to olefins, triple bonded compounds like
diphenyl acetylene were epoxidised to the unsaturated
epoxy compound in 46% yield. Product showed IR
absorption at 917, characteristic of the epoxy group and
at 1650 cm -1 (C=C str). The products were identified
in comparison with the physical constants of authentic
samples and also from IR spectral values. The epoxide
content was also determined by the estimation of oxirane
oxygen by using HCl in the presence of dioxan at various
time intervals.
The presence of metal catalysts showed remarkable
inf luen ce on the rate of e poxidatio n rea ctio ns.
Catalysts utilized for epoxidation were tried for
oxidation also. The results are presented in Table I ,
[VO (acac) 2] being sparingly soluble in dioxan could
be r emoved from the re action mixtu re only by
fractional crystallization. BTEAH could be removed
from the reaction mixture by aqueous extraction.
Though [VO (acac) 2] was found to be most effective
in terms of reaction time and product yield the
difficulty encountered with its removal from the
reaction mixture limits its application. The epoxidation
SHEELA et al.: DIVINYL BENZENE CRO SSLINKED PO LYSTYR ENE
945
Table I—Epo xidatio n of olefins using DVB-cros slinked polystyrene supported TBHP resin
O lefin
a
Reac tion time
(hr)
b
c
Product
Isolated yield
(%)
Cinnamic acid
42
Phenyl glycid ate
40
Ethylcinnamate
36
Ethyl phenyl glycidate
55
Allyl b romide
32
Ep ibromohydrin
50
Choles terol
58
Cholestenone and Epo xide
56
Styrene oxide
34
24
Cyclo hexene o xide
52
24
Epoxymethyl propio nate
50
36
Acenaphthylene o xide
40
Diphenylac etylene
36
1,2-Epo xyd iphenylethene
46
2-Chlo ro acrylonitrile
36
1-Chloro 1,2-epoxycyanoethane
45
Cinnamic acid
e
16
Phenyl glycid ate
82
Cinnamic acid
f
16
Phenyl glycid ate
85
Cinnamic acid g
12
Phenyl glycid ate
90
e
24
Cyclo hexene o xide
52
Cyclohexenef
16
Cyclo hexene o xide
84
g
16
Cyclo hexene o xide
92
Styrene
d
Cyclohexene
Methyl methacrylate
Ac enaphthylene
Cyclohexene
Cyc lohexene
d
d
a
Olefin to resin ratio, 1:2; s olvent, dioxan; temperature,70°C
b
Includes time for preswelling also
c
Characterized by comparison with authentic s amples (m.p. /b.p. & IR)
d
Temp erature, 30°C
e
Catalyst, BT EAH (1mmole)
f
Catalyst, MoO 3 (1mmole)
g
Catalyst, VO (ac ac)2 (1mmole)
reaction catalyzed by [VO (acac) 2 ] produced 90%
phenyl glycidate with cinnamic acid in 12 hr, whereas
the uncatalyzed reaction yielded only 40% epoxide
even after 42 hr. Similarly, cyclohexene yielded 92%
epoxide in 16 hr while the uncatalyzed reaction gave
only 52% yield in 24 hr.
Simple first order kinetic equation was applied to
compute the rate constants of the epoxidation reactions.
The rate constants for epoxidation of cinnamic acid in
the pre sence of [VO (acac) 2], MoO 3 and under
uncatalyzed conditions are 4.5 × 10-4, 4.1 × 10-4 and
8.8 × 10-5 sec-1 respectively. Epoxidation may be
assumed to follow pseudo first order kinetics as it was
carried out with a large excess (substrate to reagent
molar ratio, 1:10) of the TBHP. The reaction is
assumed to involve the nucleophilic attack of the olefin
on TBHP followed by the proton transfer, which is
assumed to occur by a concerted intramolecular
process. The intermediate decays to give the epoxide.
68&10
The probable mechanism for catalyzed and uncatalyzed
epoxidation is depicted in Scheme III . When the metal
catalyst comes in contact with TBHP, it results in the
formation of a metal TBHP complex. The increase in
the reaction rate might probably occur through the
nucloeophilic displacements on the electrophilic
oxygen of the O–O bond in the metal TBHP complex.
The intermediate formed as a result of this nucleophilic
attack finally decays to give the epoxide. An increase
in the coordination number, when the hydroperoxy
hydrogen is replaced by a metal ion might have
resulted in the enhancement of the reaction rate when
transition metal catalysts are used.
The effect of various reaction parameters such as
solvent, temperature and molar ratio of substrate to
resin on epoxidation of cinnamic acid was investigated.
The effect of various solvents on epoxidation reaction
is shown in Ta ble II . The details of swelling are
presented in Tab le III . Resin 1 appeared to swell
946
INDIAN J. CHEM., SEC B, APRIL 2006
C
C
C
C
C
+
O
O
O
O
H
LnM
+
L(n-1) M
O
O
+
C
L(n-1) MOR
+
R
C
C
C
C
O
C
M
OR
O
RO
C
+ LH
C
O
OH
C
L (n-1) MOOR
R OOH
+
O
C
H
C
O
M
+
RO
M
MOR
C
C
C
+
C
C
O
LnM = transition metal catalyst
Scheme III —Probable mechanism for epoxidation of olefins
m axim um in a ce ton itrile wh ile T BHP s ho we d
maximum swelling in dioxan. The efficiency of the
reagent was found to be maximum in dioxan.
Influence of temperature is shown in Ta ble IV .
Olefins containing vinyl groups, when epoxidised at
elevated temperature, resulted in the polymerized
product, instead of the epoxide. In the case of methyl
m etha cr yla te , a lm os t th e e ntir e s ub str ate go t
polymerized before epoxidation. However, at room
temperature, these substrates were epoxidised with
considerable yields. In the case of substrates like
cinnamic acid, cyclohexene, ethyl cinnamate etc, the
reaction took place only at higher temperature. At 30°C,
the epoxidation of cinnamic acid did not commence
even after 24 hr. As the temperature was raised from
50- 80°C, the product yield was found to increase from
42 - 63% in 24 hr. When the temperature was increased
further from 80°C, the yield of epoxide remained
almost constant, without showing further improvement
in efficiency.
An increase in the molar concentration of the
polymeric reagent enhanced the epoxidation reaction
to a great extent. The influence of molar ratio on
epoxidation reaction is presented in Ta ble V . The
reaction was found to be most efficient in the presence
of a five-fold molar excess of the reagent.
Oxidation Reactions . The polymeric TBHP was
used for the oxidation of alcohols to corresponding
carbonyl compounds; primary to aldehydes and
secondary to ketones in yields ranging from 56 to
84%. The results are presented in Ta ble IV . The
polymeric byproduct, t -butyl alcohol resin can be
recycled to the original reagent by a single step
without considerable loss in hydroperoxide capacity.
Oxidation of alcohols using the polymeric TBHP
and regeneration of the reagent from the spent resin
are shown in Schem e IV .
The rate of reaction was found to be diffusion
controlled and depended on the molecular size of the
substrate. Subs trates with larger molecular size
required longer period for the penetration of the
reagent function when compared to smaller substrates.
Cholesterol was oxidized to cholestenone in 58 hr
while benzhydrol and benzoin were oxidised in 36-37
hr in order to produce an yield around 80%. The
presence of substituents in the substrates markedly
affected the reaction rate. This was evidenced by the
oxidation of α-phenyl ethanol and various substituted
α-phenyl ethanols. A maximum yield of 79% was
obtained from the chloro substituted α-phenyl ethanol
while the methyl substituted one gave the minimum
yield, 50% in a period of 24 hr.
SHEELA et al.: DIVINYL BENZENE CRO SSLINKED PO LYSTYR ENE
947
Table II—Influence of nature of solvent on reagent efficiency
Reaction timea
(hr)
Yield a
(%)
Reac tion timeb
(hr)
Dio xan
16
82
38
72
Carb on tetrachlo ride
19
78
—
—
Tetrahyd rofuran
21
61
—
—
Benzene
35
53
—
—
Chloroform
22
70
36
82
Carbo n disulp hide
20
75
32
78
Dichlo romethane
19
72
34
70
Methano l
21
80
35
67
So lvent
a
Epoxidatio n of cinnamic acid; olefin to res in ratio, 1:2; catalyst, BTEAH
b
Oxid ation of benzoin, alcohol to res in ratio 1:5, temperature 70°C
Yield b
(%)
Table III—Swelling behavio ur of crosslinked p olystyrene resins
Eq uilibrium s welling factor*a
So lvent
Resin 1
Resin 4
Dichlo romethane
9.85
4.05
Tetrahyd rofuran
6.93
3.90
Chloroform
4.76
3.20
Dio xan
3.98
4.68
Carb on tetrachlo ride
3.13
2.04
2.98
1.36
11.36
4.12
Benzene
Aceto nitrile
a
* Swelling time, 20 hr; = (m-m0)/ m0 = weight before swelling; m= weight after swelling
Oxidation reactions were also found to be influenced
strongly by the presence of a catalyst as in the case of
epoxidation. Oxidation of benzoin and benzhydrol were
selected for this investigation. The use of a catalyst is
found to afford more or less similar yield of the product
in a much shorter reaction period. With BTEAH,
benzhydrol yielded 87% benzophenone in 18 hr while
the uncatalyzed reaction required 37 hr to give 84%
benzophenone. BTEAH and [VO(acac) 2 ] were found
to be highly efficient in the oxidation of alcohols
yielding almost quantitative amounts of the carbonyl
compounds. A similar rate enhancement effect was
observed during the oxidation of benzoin to benzil.
R ea ctio n pa ra me te rs like n atur e of s olve nt,
temperature and molar concentration of reagent
influenced oxidation reactions also. Influence of the
nature of solvent on oxidation of benzoin to benzil is
shown in Ta ble II . The percentage conversion of
benzoin was found to be maximum in acetonitrile. The
polystyrene matrix showed maximum swelling in
acetonitrile.
The influence of temperature on the oxidation of
alcohols is shown in Table V . The time for maximum
c on ve rs io n wa s re du ce d co ns id er ab ly a s th e
temperature was increased. The amount of benzil
obtained by oxidation of benzoin in the presence of
various concentrations of the reagent was measured by
spectrophotometric method. Details of the reaction are
presented in Table VI. The amount of benzil obtained
increased with an increase in the effective concentration
of the resin.
Thus, DVB crosslinked polystyrene supported
t - bu tyl h yd r op er o xide re age nt w a s em p lo ye d
successfully in oxidation and epoxidation reactions
with an efficiency comparable to that of its monomeric
counterpart. The presence of transition metal catalysts
enhanced the reaction rate in both epoxidation and
o xida tio n re ac tio ns . Bas ed o n the f o re go in g
948
INDIAN J. CHEM., SEC B, APRIL 2006
Table IV— Oxidation of alc ohols using DVB cros slinked polys tyrene supported TBHP resin
Alcoho la
Reac tion timeb
(hr)
Productc
Isolated yield
(%)
Benzoin
36
Benzil
Choles terol
58
Cholestenone & Epo xide
Benzhydrol
37
Benzop heno ne
84
Benzyl alco hol
20
Benzald ehyde
83
α -P henylethanol
p -Nitro-α -p henyl ethanol
24
Acetophenone
73
24
p -Nitroaceto phenone
56
p -Chlo ro-α -phenyl ethanol
24
p -Chloroacetophenone
79
p -Methyl-α -p henyl ethanol
24
p -Methylacetopheno ne
50
p -Methoxy-α -p henyl ethanol
24
p -Methoxyacetophenone
60
Benzoin
d
16
Benzil
82
Benzo in e
22
Benzil
80
Benzo in f
15
Benzil
85
d
Benzhyd ro l
18
Benzop heno ne
87
Benzhyd ro le
20
Benzop heno ne
83
f
21
Benzop heno ne
80
Benzhyd ro l
a
Alco hol to resin ratio 1:5; so lvent, chloro form; temperature, 70°C
b
Includes time for preswelling also
c
Characterized by comparison with authentic samples (m.p./b.p. & IR)
d
Catalyst, BT EAH (1mmole)
e
Catalyst, MoO 3 (1mmole)
f
Catalyst, [VO (ac ac)2 ] (1mmole)
82
CH3
R
CHOH
CH2
+
C
72&12
Substrate to resin, 1:5,
Chloroform, 700C
OOH
R
CH3
CH2
C
CH3
OH
+
R
C=O
R
R = alkyl, aryl
CH3
R = alkyl, aryl or H
Scheme IV —Oxidation of alcohols using polymeric t-butyl hydroperoxide reagent
observations it may be concluded that DVB crosslinked
polystyrene supported TBHP is a successful solid
phase organic reagent which utilizes the unique
features o f the macromo lecula r system and the
efficiency of the TBHP moiety.
M aterials and M ethods
The monomers were purified by low-pressure
distillation. Solvents used were of reagent grade and
were purified according to literature procedures. IR
spectra were recorded on a Perkin–Elmer 897 model
spectrometer using KBr pellets. 2% DVB crosslinked
p olys tyr en e w as pr ep ar e d by su sp e ns io n
polymerization and functionalized with t- butyl alcohol
moiety by polymer analogous reactions reported
earlier 14 .
Experimental Section
P reparation of TBHP resin . 2% DVB crosslinked
p olys tyr en e w as pr ep ar e d by su sp e ns io n
SHEELA et al.: DIVINYL BENZENE CRO SSLINKED PO LYSTYR ENE
949
Table V — Influence of temperature on reagent efficiency
Temperaturea
O
C
Yield a
%
30
Temperatureb
O
C
Yield b
%
No reaction
48
68
40
—
45
68
50
42
41
75
60
48
38
80
70
56
36
82
80
63
reflux
63
—
—
—
—
a
Epoxidation of cinnamic acid; substrate to molar ratio
b
Oxidation of benzoin to benzil; molar ratio, 1:5; solvent, chloroform
; solvent, dioxan, reaction time, 24 hr
Table VI—Influence of molar ratio on reagent efficiency
Molar ratio
a
b
Reaction timea
(hr)
Yield a
Yield b
(%)
Reac tion timeb
(hr)
( %)
1:1
42
62
49
63
1:2
39
58
46
68
1:3
38
61
40
70
1:4
36
63
38
78
1:5
32
69
36
82
Epo xidatio n of cinnamic acid; s olvent, dioxan; temp erature, 70°C
Oxidation of benzoin to benzil; solvent chloroform; temperature, 70°C
polymerization. Styrene (18.68 mL), DVB (0.95 mL)
and benzoyl peroxide (250 mg) were added to the
solution of poly(vinyl alcohol),(150 mg) in water (100
mL) kept at 80-90°C and stirred vigorously for 16 hr.
The bead shaped polystyrene 1 precipitated was
filtered, washed with various solvents and dried at
70 ° C in vacuum. 10 g of the dried beads were
suspended in a 4:1 v/v mixture of CS 2 and CH2Cl2 for
12 hr. Bromoacetone (20 g) in solvent mixture (20 mL)
taken in an RB flask was cooled in an ice-bath and
anhydrous AlCl3 (20g) added to it in small portions
with vigorous stirring. The preswollen polymer was
then added to the cold mixture with continuous stirring.
The mixture was then stirred at room temperature and
heated under reflux for 6 hr. It was then added to
aqueous ethanol to break the Lewis acid complex. The
2-oxopropyl resin was collected on a sintered glass
filter and washed with different solvents and dried in
vacuum. The oxopropyl polystyrene (5 g) preswollen
in THF for 12 hr was added to the freshly prepared
Grignard reagent prepared from methyl iodide (6 mL)
and heated under reflux for 6 hr. The reaction mixture
was then cooled, filtered and washed with dilute
H2SO 4, water and organic solvents. The t-butyl alcohol
resin was dried in vacuum.
P reparation of t-butyl hydroperoxide resin . The
t-butyl alcohol resin was suspended in THF (30 mL)
for 12 hr. The suspension was cooled in an ice-bath
and 70% H2SO4 (10 mL) was added drop wise with
mild shaking. The mixture was kept for 10 minutes
and 30 vol H2O2 (10 mL) was added to it. The reaction
mixture was brought to room temperature and stirred
for 10 hr. The resin was filtered, washed with water
(20 mL × 3 times), THF (20 mL × 3 times) methanol
(20 mL × 3 times) and acetone (20 mL × 3 times) and
dried in vacuum.
Epoxid ation of olefins . The olefin (1 mmole) in
dioxan (30 mL) was stirred with a two-fold molar excess of TBHP resin. The reaction was monitored by
TLC as well as by estimating the residual hydroperoxide capacity. After the completion of the reactions, resin
was filtered and washed with dioxan (10 mL × 3 times).
The combined filtrate and washings on evaporation of
the solvent afforded the corresponding epoxides.
950
INDIAN J. CHEM., SEC B, APRIL 2006
Oxidation of alcohols: General pro cedure . The
alcohol (1 mmole), dissolved in chloroform (20 mL),
was stirred with a five-fold molar excess of the TBHP
resin. The reaction was followed by TLC. After the
completion of the reaction, the resin was filtered and
washed with chloroform. The combined filtrate and
washings on evaporation of the solvent afforded the
corresponding compounds.
Acknowledgement
The authors thank the CSIR, New Delhi for a
Fellowship to one of the authors ( MSS) .
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