Radical-induced oxidation of RAFT agentsa - A kinetic study

Article abstract of DOI:10.1002/pola.24554

Radical-induced oxidation of reversible addition-fragmentation chain transfer (RAFT) agents is investigated with respect to the effect of molecular structure on oxidation rate. The radicals are generated by homolysis of either azobisisobutyronitrile or alkoxyamine and transformed in situ immediately into peroxy radicals through transfer to molecular oxygen. It is found that the oxidation rate depends on the structure of Z- and R-group of thiocarbonylthio compounds. For dithioesters with identical Z-phenyl substituent, the oxidation rate decreases in the order of cyanoisopropyl (-C(Me)₂CN) > cumyl (-C(Me)₂Ph) > phenylethyl (-CH(Me)Ph) > 2-methoxy-1-methyl-2- oxoethyl (-CH(Me) -C(=O)OCH₃) > benzyl (-CH₂Ph). For dithioesters with identical R-group, the oxidation rate decreases in the order of Z = phenyl- ～ benzyl- > RS- (trithiocarbonates) > RO- (xanthates). The stability of the RAFT agents toward oxidation correlates well with the chain transfer abilities as those previously reported by Rizzardo and coworkers. The priority of the oxidation reaction over the RAFT process, and the subsequent influence on RAFT polymerization are also investigated.

Full text of DOI:10.1002/pola.24554

Radical-Induced Oxidation of RAFT Agents—A Kinetic Study
CHANGXI LI,1,2 JUNPO HE,1,2 YANWU ZHOU,1,2 YUANKAI GU,1,2 YULIANG YANG1,2
1Key Laboratory of Molecular Engineering of Polymers at Fudan University, Ministry of Education, Shanghai 200433, China
2Department of Macromolecular Science, Fudan University, Shanghai 200433, China
Received 20 October 2010; accepted 20 December 2010
DOI: 10.1002/pola.24554
Published online 18 January 2011 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: Radical-induced oxidation of reversible addition-
fragmentation chain transfer (RAFT) agents is investigated with
respect to the effect of molecular structure on oxidation rate.
The radicals are generated by homolysis of either azobisisobu-
tyronitrile or alkoxyamine and transformed in situ immediately
into peroxy radicals through transfer to molecular oxygen. It is
found that the oxidation rate depends on the structure of Z-
and R-group of thiocarbonylthio compounds. For dithioesters
with identical Z-phenyl substituent, the oxidation rate
decreases in the order of cyanoisopropyl (AC(Me)2CN) > cumyl
For dithioesters with identical R-group, the oxidation rate
decreases in the order of Z ¼ phenylꢀ ꢁ benzylꢀ > RSꢀ (tri-
thiocarbonates) > ROꢀ (xanthates). The stability of the RAFT
agents toward oxidation correlates well with the chain transfer
abilities as those previously reported by Rizzardo and co-
workers. The priority of the oxidation reaction over the RAFT
process, and the subsequent influence on RAFT polymerization
C
V
are also investigated.
2011 Wiley Periodicals, Inc. J Polym
Sci Part A: Polym Chem 49: 1351–1360, 2011
(AC(Me)2Ph)
>
phenylethyl (ACH(Me)Ph)
>
2-methoxy-1-
KEYWORDS: kinetics; molecular structure; oxidation; RAFT; radi-
methyl-2-oxoethyl (ACH(Me) AC(¼O)OCH3) > benzyl (ACH2Ph).
cal polymerization
INTRODUCTION Thiocarbonylthio compounds are widely
used mediating agents in controlled/‘‘living’’ radical polymer-
ization based on reversible addition-fragmentation chain
transfer (RAFT) process.1,2 The thiocarbonylthio moieties
retain at the chain end of the polymerization product. The
stability of the thiocarbonylthio compounds has attracted
much attention, because it relates not only to the chain end
functionality but also to the possible chain degradation of
the polymerization product.3,4 The fidelity of thiocarbo-
nylthio moieties at the chain ends has been proven by
NMR5,7 and MALDI-TOF or ESI-MS.8–17 These functionalities
can be removed deliberately by aminolysis,18–27 hydroly-
sis,28,29 and reduction,30–32 aiming to improve the degrada-
tion stability of the product or obtain a mercapto end group.
Systematic studies19,33–40 using thermogravimetric analysis
(TGA) have revealed that dithioesters undergo thermal
decomposition at carbon-sulfur single bond, which is then
used to completely remove thiocarbonylthio terminus of
RAFT polymerization products.19,37–40 Thermal decomposi-
tion may also occur during polymerization, although to a
much less extent, causing retardation and broadened molec-
ular weight distribution.34 The removal of thiocarbonylthio
terminus for stabilization purpose is also achieved by post-
treatment of polymer products with tributylstannane,40 azo-
bisisobutyronitrile (AIBN)41–43 or by ultraviolet radia-
tion,44,45 which involves radical disproportionation process
that form saturated or unsaturated chain ends.42,46
In the background of organic chemistry, it has been reported
that thiocarbonyl group can be converted into carbonyl
group by a number of oxidizing agents, such as inorganic
and organic peroxides, as well as molecular oxygen under
irradiation.47 Recently, Vana and coworkers performed oxida-
tion reaction of the dithioester end group of poly(methyl
methacrylate) (PMMA) using tert-butyl hydroperoxide.8 Zard
and coworkers48 achieved high yielding carbonyl group from
thiocarbonyl group in xanthates by ozonolysis. Barner-
Kowollik and coworkers49 used the oxidation reaction
induced by AIBN-derived radical in air in the presence of
THF to prepare hydroxyl end-functionalized polymer. These
findings pave a new way to functionalize RAFT polymer
product.
It is important to note that AIBN-induced oxidation of thio-
carbonylthio may relates to many reaction processes in
RAFT-based polymerization. Trace amount of oxygen due to
incomplete deaeration may lead to partial oxidation of the
RAFT agent. This could be one of the reasons for the observa-
tion of thioester species in mass spectrometry,10–13,15,16,50–52
although peroxides in solvent tetrahydrofuran (THF) used for
mass spectroscopy may also results in formation of thio-
ester. AIBN treatment of RAFT polymerization product to
remove thiocarbonythio termini41 may also result in thio-
ester moieties that retain at the chain ends. The preparation
of dithioesters possessing leaving group derived from AIBN,
for instance 2-cyanoprop-2-yl dithiobenzoate (CyDB), by the
Additional Supporting Information may be found in the online version of this article. Correspondence to: J. He (E-mail: jphe@fudan.edu.cn)
C
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Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 49, 1351–1360 (2011) 2011 Wiley Periodicals, Inc.
RADICAL-INDUCED OXIDATION OF RAFT AGENTS, LI ET AL.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
RAFT process53 may form oxidized byproduct in the presence
of oxygen.
perature were both 230 ꢂC. The electron multiplier voltage
was set on 70 eV.
It is thus necessary to investigate the oxidation kinetics and
affecting factors to achieve better control on the RAFT-based
polymerization. The relationship between stability and mo-
lecular structure will be helpful for the development of
‘‘more oxygen tolerant’’ RAFT agents. The basic knowledge of
the oxidation is also vital to the kinetic study of the RAFT
process initiated by alkoxyamine, a model reaction developed
in our laboratory.54 In the present work, a series of thiocar-
bonylthio compounds with different leaving and activating
groups are subject to radical induced oxidation. The depend-
ence of oxidation rate on molecular structure, as well as the
influence of the oxidation on RAFT polymerization, will be
discussed.
Matrix-assisted laser desorption ionization time-of-flight
mass spectroscopy (MALDI-TOF MS) analysis were per-
formed on a Voyager-DE STR (Applied Biosystems, Framing-
ham, MA) equipped with a nitrogen laser emitting at 337 nm
with a 3-ns pulse duration. The instrument was calibrated
with Angiotensin and Insulin and operated in the reflector
mode. The accelerating potential is 20 kV. For each spectrum,
1000 laser shots were accumulated. The matrix used was R-
cyano-4-hydroxycinnamic acid (CHCA). Samples were pre-
pared by mixing the solution of polymer (5 lL, 10 mg/mL
in CHCl3), the matrix (45 lL, 10 mg/mL in methanol) and
sodium trifluoroacetate (STFA, cationizing agent, 5 lL, 10
mg/mL in methanol). An aliquot of 1 lL of the resulting mix-
ture was spotted on the gold plate and air-dried.
EXPERIMENTAL
Syntheses of the RAFT Agents
Materials
All RAFT agents were synthesized according to litera-
ture.53,56–58 The characterization results of 1H NMR, FTIR,
and GC-MS are given in Supporting Information.
AIBN (Shanghai 4th Factory of Chemicals, 99%) was recrys-
tallized from methanol. Methanol (Lingfeng Chemicals,
99.5%), petroleum ether (60–90 C range, Shenxiang Chemi-
ꢂ
Oxidation Reaction of RAFT Agents
cals, 99%), and dichloromethane (Lingfeng Chemicals, 99%)
were dried over CaCl2 and distilled before use. Cyclohexane
(Feida, 99.5%), benzene (Shenxiang Chemicals, 99%) and tol-
uene (Lingfeng Chemicals, 99%) was dried over sodium and
distilled before use. Methyl methacrylate (MMA, Shanghai
Fourth Factory of chemicals, 98%) and styrene (Yonghua
Special Chemicals, 99%) were distilled after being stirred
over CaH2 for 24 h.
Thiocarbonylthio compounds (as listed in Table 1; 0.1 mmol)
and AIBN (0.032 g, 0.2 mmol) were dissolved in benzene
(10 mL) in a 100-mL flask, which was then sealed without
degassing. The reaction mixture was heated at 60 ꢂC for a
predetermined period.
Oxidation Reaction of PEDB in the
Presence of Alkoxyamine
1-Phenylethyl dithiobenzoate (PEDB; 0.026 g, 0.1 mmol) and
1-(2,2,6,6-tetramethylpiperidinyloxy)-1-phenyl-ethane (PEET;
synthesized according to literature procedures55; 0.065 g,
0.4 mmol) were dissolved in cyclohexane (10 mL) in a 100-
mL flask, which was then sealed without degassing. The
Measurements
High-performance liquid chromatography (HPLC) was per-
formed on an instrument composed of a Waters 515 pump,
a C-18 column and a UV detector with the wavelength set at
254 and 300 nm. Acetonitrile/water (v/v ¼ 85/15) mixture
was used as eluent (1.0 mL/min) at 40 ꢂC. 1H NMR and
13C NMR were carried out on a Bruker (500 MHz) NMR
instrument, using tetramethylsilane (TMS) as the reference.
Gel permeation chromatography (GPC) was performed on a
Waters 410 system equipped with a guard column and three
TSK columns (TSK Gel H-type, pore size 15, 30, and 200 Å)
in series, a Waters 410 RI detector, using THF as the eluent
ꢂ
reaction mixture was heated at 90 C for a period of 16 h.
Oxidation Reactions of Polymeric RAFT
Agents, PMMA-RAFT, and PS-RAFT
PMMA-RAFT (0.280 g, 0.1 mmol) and AIBN (0.065 g, 0.4
mmol) were dissolved in benzene (10 mL) in a 100-mL flask,
which was then sealedꢂ without degassing. The reaction mix-
ture was heated at 60 C for 4 h before quenched into liquid
nitrogen to stop the reaction.
ꢂ
at a flow rate of 1 mL/min at 40 C. The columns were cali-
brated by narrow polystyrene standard with molecular
weight ranging from 2.2 ꢃ 103 to 5.2 ꢃ 105 g/mol. Gas chro-
matography–mass spectrometry (GC-MS) was performed on
an Agilent Technologies 6890N system, equipped with a
mass-selective detector using electron impact ionization.
Analytes were separated by a HP-5MS capillary column of 30
m (0.25 i.d. and 0.25-lm film thickness), which was inserted
directly into the ion source of the MS system. Helium
(99.999%) was the carrier gas maintained at a flow-rate of
1.0 mL/min. The injector was kept at 280 ꢂC, and samples
were split injected (1 lL, split ratio 100:1). The column oven
temperatureꢂ was programmed to start at 80 ꢂC for 2 min,
PS-RAFT (0.228 g, 0.1 mmol) reacts with AIBN under the
same conditions as in PMMA-RAFT system.
RESULTS AND DISCUSSION
The Oxidation of Thiocarbonylthio
Compounds Initiated by AIBN
The oxidation reactions are performed by heating the solu-
tion of RAFT agents, either small molecular or polymeric, in
the presence of air and AIBN. The results are listed in Table
ꢂ
1. As an example, PEDB, which is stable in air up to 100 C
in the absence of AIBN (run 1 in Table 1), is completely oxi-
dized at 60 ꢂC within 8 h in the presence of both air and
AIBN. The oxidation reaction is monitored by ultraviolet–visi-
ble spectroscopy (UV–vis) and high-performance liquid
ꢂ
ꢂ
ramp at 10 C/min to 280 C, and held at 280 C for 5 min.
EI spectra were scanned between 50 and 550 Da in the full-
scan acquisition mode. The transfer line and EI source tem-
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TABLE 1 Experimental Conditions and Results of Oxidation Reaction
Radical Feed
Source Molar Ratio Atmosphere (ꢂC)
Temperature Reaction
Run Dithioestera
1
Time (h) Solvent
Product
–
–
air
100
80
60
60
60
60
60
60
16
4
tert-butyl benzene no reaction
2
3
4
5
6
7
8
AIBN
AIBN
AIBN
AIBN
AIBN
AIBN
AIBN
1:10
1:2
1:2
1:2
1:2
1:2
1:2
N2
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
air
Air
Air
Air
Air
Air
8
8
8
4
3
10
9
AIBN
AIBN
1:2
1:2
Air
Air
60
60
38
46
Benzene
Benzene
10
11
12
13
AIBN
PEET
PEET
1:2
1:4
1:4
O2
Air
N2
60
90
90
5
Benzene
16
8
Cyclohexane
Cyclohexane
14
15
a
PS-RAFTb
PMMA-RAFTb
AIBN
AIBN
1:4
1:4
Air
Air
60
60
4
4
Benzene
Benzene
PS-thioester
PMMA-thioester
b
PEDB, CDB, BDB, CyDB were synthesized according to literature ref.
53. BDES was synthesized according to literature ref. 56. DBTTC was
synthesized according to literature ref. 57. EtoCDB was synthesized
according to literature ref. 58.
PS-RAFT and PMMA-RAFT are polystyrene(Mn,GPC ¼ 2280 g/mol, Mw
/
Mn ¼ 1.10) and poly(methyl methacrylate) (Mn,GPC ¼ 2800 g/mol, Mw/Mn
¼ 1.14), respectively, prepared by RAFT polymerizations mediated by
cumyl dithiobenzoate (CDB).
chromatography (HPLC). As shown in Figure 1, the absorp-
tion band at 300 nm of dithioester decreases along with
time and finally disappears at 8 h. The solution changes
from pink to light yellow in color (inset in Fig. 1). This cor-
responds to a decrease in PEDB peak and an increase in a
new peak at retention time ¼ 6.4 min in HPLC diagram. 1H
NMR spectrum in Figure 2 shows all aromatic, methyl and
methine protons, whose chemical shifts and integration val-
ues correlates to the expected oxidized structure. More
importantly, the structure of thioester in the oxidation prod-
uct is confirmed by the presence of signals at d ¼ 191 ppm
in 13C NMR spectrum [Fig. 2(b)], which is assigned to car-
bonyl group (The signal for thiocarbonyl group should be at
ꢁ234 ppm59). Figure 3 shows the gas chromatography-mass
spectroscopy (GC-MS) results, in which the molecular ion at
m/z ¼ 242 is assignable to the anticipated oxidation prod-
uct, 1-phenylethyl benzothioate (PEBT), while the base peak
is benzoyl cation (m/z ¼ 105).
All of the RAFT agents in Table 1 undergo oxidation in a way
in which carbonyl sulfur is replaced by oxygen. This desul-
furization of thiocarbonyl moiety in dithioesters has long
RADICAL-INDUCED OXIDATION OF RAFT AGENTS, LI ET AL.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
FIGURE 1 UV–vis spectrometry
(a) and HPLC (b) monitoring the
oxidation reaction of PEDB (0.026
g, 0.1 mmol) and AIBN (0.032 g,
0.2 mmol) in benzene at 60 ꢂC in
the presence of air. The insets
are snapshots of the reaction
vessels
showing
the
color
change during the reaction.
been achieved using oxidation reagents such as
Hg(CH3COO)2, KMnO4, and meta-chloroperoxybenzoic acid.60
Nevertheless, the study on radical induced oxidation, as that
in the present case, in the RAFT system is still scarce.8,49 It
is also noted that azo-type radical initiator such as AIBN are
widely used to create the peroxy radical oxidation environ-
ment in organic and pharmaceutical chemistry.61 The same
species, that is, the peroxy radical, is supposed to be the oxi-
dizing agent in the present work. Thus, the peroxy radical
adds to thiocarbonylthio moiety to form an intermediate rad-
ical, which cyclizes into oxathiirane62 and expels a cyanoiso-
propoxy radical. The oxathiirane transforms into more stable
carbonyl moiety and releases sulfur.62 Indeed, yellowish solid
was observed on the wall of the flask during oxidation reac-
tion. One of the possible further pathway of the expelled cya-
noisopropoxy radical is to react with thiocarbonythio moiety
again, forming another carbonyl species through the oxathiir-
ane intermediate, and expel a cyanoisopropyl radical. The
overall oxidation reaction process is tentatively proposed in
Scheme 1.
kinetics under parallel conditions. The concentration of per-
oxy species, [peroxy], is assumed to be on a steady state at
the initial stage. The conversion rate of thiocarbonylthio moi-
ety (C(¼¼S)S) is expressed by:
ꢀ
ꢁ
½Cð¼ SÞSꢄ
½Cð¼ SÞSꢄ0t
ln
¼ kox½peroxyꢄt
(1)
The linearity in kinetic plots in Figures 4 and 5 indicates the
applicability of the steady state assumption. Increase the
concentration of oxygen results in higher concentration of
peroxy radical. Therefore, the reaction in the presence of
pure oxygen displays faster rate than that under air, as
shown in the case of PEDB (Fig. 4).
It is interesting to find that the reaction rate depends on
chemical structure, that is, the structure of leaving (R-)
and stabilizing (Z-) groups, of the thiocarbonylthio com-
pounds. For dithioesters with identical Z-phenyl substituent
(run 3–7 in Table 1), the conversion rate estimated from
the slop in Figure 4 decreases in the order of cyanoiso-
propyl (AC(Me)2CN) > cumyl (AC(Me)2Ph) > phenylethyl
(ACH(Me)Ph) > 2-methoxy-1-methyl-2-oxoethyl (ACH(Me)
AC(¼¼O)OCH3) > benzyl (ACH2Ph). This is surprisingly the
same order of the leaving ability of R-group, or chain trans-
fer coefficients of dithioesters, as that previously reported by
Rizzardo and coworkers.53 The effect of R-group on the oxi-
dation rate of dithioesters is unexpected because the leaving
group is apart from thiocarbonyl sulfur atom by two r- and
one p-bonds. This indicates that the R-group is able to either
activate the thiocarbonyl or stabilize the reaction
Influence of Molecular Structure on Oxidizability of
Thiocarbonylthio Compounds
The oxidation rate of dithioester is a function of concentra-
tions of dithioester and peroxy species. Thus, the conversion
rate exhibits a decaying mode along with reaction time due
to consumption of AIBN and oxygen. Nonetheless, dithioest-
ers are readily oxidized to 100% conversion, provided that
the peroxy species is enough. The oxidizabilities of various
thiocarbonylthio compounds are compared by measuring the
FIGURE
2
1H- (a) and 13C- (b)
NMR spectra of the oxidation
product, PEBT. (The signals with
star symbol are from purification
solvent, cyclohexane).
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ARTICLE
FIGURE 4 Kinetic plots of oxidation reactions for RAFT agents
with identical Z (phenyl) group but different R group. The oxi-
dation rate decreased in the order of CyDB (R ¼ AC(Me)2CN) >
CDB (R ¼ AC(Me)2Ph) > PEDB (R ¼ ACH(Me)Ph) > MADB (R ¼
ACH(Me)AC(¼O)OCH3) > BDB (R ¼ ACH2Ph).
FIGURE 3 Gas chromatography-mass spectroscopy (GC-MS)
spectra of PEBT.
intermediate. Because there is no previous report or evi-
dence on the presence and structure (if any) of intermediate
in the desulfurization, we will try to explain the fact accord-
ing to the ab initio study63–66 on the influence of R-group on
the stability of thiocarbonylthio compounds. We hereby
assume that the susceptibility of thiocarbonyl toward peroxy
radicals is similar to that toward carbon-centered radicals.
As pointed out by Coote,63 the substituent can affect the sta-
bility of the thiocarbonythio compound through both elec-
tronic and steric factors. A strong electron-withdrawing
group, such as cyano group in AC(Me)2CN, would reduce the
electron donating ability of R-group and, therefore, reduce
the stability of C¼¼S bond via the resonance structures
(Scheme 2).
From the results in Table 1 and Figure 5, it is clear that the
ease of oxidation is also dependent on the nature of the Z
substituent of the RAFT agents. BDB and DBTTC have identi-
cal leaving group. The former is completely oxidized within
8 h, whereas the latter needs 38 h. EtoCDB shows the high-
est stability, reaching a conversion of 73% within 46 h.
Thus, the stability of the RAFT agents toward oxidation
increases in the order Z ¼ phenyl– ꢁ benzyl– < RS– (trithio-
carbonates) < RO– (xanthates). This again correlates with
the reactivity of thiocarbonylthio compounds in the RAFT
polymerization,67,68 albeit in an inverse order. As previously
reported, the apparent chain transfer coefficients of
dithioesters with Z ¼ phenyl are in the range of 190–
500,53,69 while trithiocarbonates is 53.70 Xanthates are only
effective to more active radicals such as poly(vinyl acetate)
propagating radical but unable to mediate the polymeriza-
tion of styrene and (meth)acrylates.
Thus, CyDB is most easily oxidized in comparison with other
dithioesters. Substituents AC(Me)2Ph, ACH(Me)Ph, and
ACH2Ph with different methyl groups affect the stability of thio-
carbonylthio compounds by distorting the rigid S¼¼CAS planar
system. More bulky substituents lead to more distorted planar
system and lower stability of the corresponding compounds.
The agreement between the reactivity of thiocarbonylthio com-
pounds in oxidation and in RAFT polymerization reflects the
FIGURE 5 Kinetic plots of oxidation reactions for RAFT agents
possessing different Z groups. The oxidation rate decreases in
the order of PEDB (phenyl dithiobenzoate) ꢁ BDES (benzyl
SCHEME 1 The proposed AIBN-initiated oxidation reaction pro-
cess of the RAFT agents. [Color figure can be viewed in the
online issue, which is available at wileyonlinelibrary.com.]
dithiobenzoate)
(xanthates).
>
DBTTC (trithiocarbonates)
>
EtoCDB
RADICAL-INDUCED OXIDATION OF RAFT AGENTS, LI ET AL.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
SCHEME 2 The resonance structure of the thiocarbonylthio
compound.
SCHEME 3 The zwitterionic canonical form of xanthate.
electronic feature of molecular orbital. The stabilities of xan-
thates and trithiocarbonates are associated with the electron
donating abilities of lone pair substituents, alkylthio and alkoxy
groups, through the resonance structure64,67,71–78 (Scheme 3).
Other radical source, such as alkoxyamine, gives similar
results. Heating PEDB and PEET (1-(2,2,6,6-tetramethylpiper-
idinyloxy)-1-phenyl-ethane) in a well-deaerated cyclohexane
solution results in no change of HPLC diagram (Supporting
Information) because the leaving groups in the reactants are
identical. However, in the presence of air, the reaction gives
the oxidized product, PEBT. The pink color of PEDB fades
and the solution becomes light yellow, whereas UV–vis spec-
trum [Fig. 6(a)] indicates the disappearance of the character-
istic absorption band of thiocarbonylthio moiety. In addition,
thioester with R-group derived from the solvent, cyclohexyl
benzothioate (CHBT), is observed by HPLC [Fig. 6(b)] with
the characterization by LC-MS (Fig. 7), GC-MS and NMR (Sup-
porting Information). CHBT is formed through a process sim-
ilar to that proposed by Barner-Kowollik.49 It is interesting
to note that the formation of CHBT lags obviously behind
the primary oxidation product, PEBT. This indicates that per-
oxy radical, formed from PEET-released phenylethyl radical
and oxygen, would attack preferentially thiocarbonyl group
rather than cyclohexane. Nevertheless, once a cyclohexyl rad-
ical is generated, it will undergo the RAFT process with the
residual PEDB, resulting in cyclohexyl dithiobenzoate, which
will be quickly oxidized to CHBT.
The resonance will remarkably raise the energy of LUMO
(and HOMO) and reduce the reactivity of C¼¼S toward radical
addition.67 Indeed, the partial charge on sulfur of the C¼¼S is
more negative, as calculated by Rizzardo67 and Coote63 using
different levels of theory. The strongest deactivating effect is
given by alkoxy substituent. Thus, xanthates are the most
stable thiocarbonylthio compounds toward oxidation by per-
oxy radicals. Trithiocarbonates follows but are more stable
than dithioesters.
A remarkable feature of the reaction is the high selectivity
preferring radical-induced oxidation rather than RAFT pro-
cess between AIBN-derived cyanoisopropyl radical and thio-
carbonythio compounds. The starting materials are con-
verted nearly completely to thioesters under the reaction
conditions. The selectivity may be due to following reasons:
(1) The RAFT process of cyanoisopropyl radical with
dithioesters is very slow because cyanoisopropyl itself is a
much better leaving group than others53; (2) The cyanoiso-
propyl radical generated from AIBN homolysis is trapped
very quickly by molecular oxygen to form the peroxy radical,
which will react readily with the C¼¼S group in thiocarbo-
nylthio compound. If the oxidation is carried out in proton-
donating solvent, such as THF49 or cyclohexane (vide infra),
thioesters from dithioester precursors formed through the
RAFT process with solvent-derived radicals are observed.
Therefore, it seems that the property of cyanoisopropyl radi-
cal as the best leaving group, and the use of relatively inert
solvent, benzene, lead to formation of carbonylthio species
free of byproducts and, consequently, facilitate the compari-
son of oxidation stability of various RAFT agents in the pres-
ent work.
We have also tried to conduct the oxidation reaction initiated
by UV irradiation. Thus, benzene solutions of PEDB and
BDES were irradiated by UV of 300–600 nm in the presence
of air for 8 h, respectively, then analyzed by HPLC and GC-
MS in the same way as that initiated by AIBN. Surprisingly,
no oxidized product was observed even after the disappear-
ance of the feed dithioesters, possibly because the oxidation
product is decomposed to very low molecular weight species
by UV irradiation. Indeed, there is no signal detected in GC
as well. Nonetheless, more work should be done after these
preliminary results to understand the mechanism of the
reaction under UV irradiation.
FIGURE 6 UV–vis spectrometry
(a) and HPLC (b) monitoring the
reaction of PEDB (0.024 g, 0.1
mmol) and PEET (0.032 g, 0.2
mmol) in cyclohexane at 90 ꢂC in
the presence of air.
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FIGURE 7 LC-MS characterization
of the reaction products of PEDB
(0.024 g, 0.1 mmol) and PEET
(0.032 g, 0.2 mmol) in cyclohex-
ane at 90 ꢂC in the presence of
air.
FIGURE 8 UV–vis spectra (a) and GPC
diagrams (b) of PMMA-RAFT (Mn
¼
2800 g/mol, Mw/Mn ¼ 1.14) before and
after heating with AIBN in benzene in
the presence of air. Reaction condi-
tions: PMMA-RAFT: 0.28 g, 0.1 mmol;
AIBN: 0.065 g, 0.4 mmol, 60 ꢂC for
4 h.
Radical-Induced Oxidation of Dithioesters Terminus of
Polymerization Product and Its Effect on RAFT
Polymerization
assignable to oxidized products, for example, PMMA with
different x-end groups but the same thioester terminus
(Table 2).
Dithioester terminus of the RAFT polymerization products
undergoes oxidation readily as well in the presence of radi-
cal and oxygen. Heating polystyrene or PMMA, prepared by
cumyl dithiobenzoate-mediated RAFT polymerization, to-
gether with AIBN in benzene solution at 60 ꢂC in the pres-
ence of air results in rapid oxidation of dithioester moiety as
indicated by UV–vis, whereas the polymer molecular weights
remain nearly unchanged (Figure 8). In addition, Figure 9
shows the MALDI-TOF MS spectrum of PMMA product, in
which the main series (P1) and a minor series (P3) are
The high content of oxidized product is reminiscent that
these species may also be formed readily during the RAFT
polymerization system where deaeration has not been well
done. This would lead to reduced controllability of the RAFT
polymerization. To inspect the issue, two parallel experi-
ments are carried out in which one system is well deaerated
before polymerization under nitrogen and the other poly-
merizes in the presence of air. As shown in Figure 10, the
former system seems to polymerize through RAFT process,
FIGURE 9 Matrix-assisted laser
desorption ionization time-of-
flight mass spectrum (MALDI-
TOF MS) of oxidation product of
PMMA-RAFT (Mn ¼ 2800 g/mol,
Mw/Mn ¼ 1.14) in the presence of
AIBN and air in benzene. (a: full
view, b: partial enlargement.).
RADICAL-INDUCED OXIDATION OF RAFT AGENTS, LI ET AL.
1357

JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
TABLE 2 Assignment of Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass
Spectrum of Oxidation Product of PMMA-RAFT
Monoisotopic Mass
Degree of
Peak
P1
Exp.
Theo.
Structure
Ion
Na
Polymerization
1929.4
1929.7
17
P2
P3
1944.5
1980.4
1944.8
1980.7
Na
Na
18
17
P4
2000.4
2012.6
2002.0
2011.8
H
20
18
P5
Na
exhibiting a stepwise increase in molecular weight, whereas
the latter exhibits uncontrolled character in which the molec-
ular weight remains nearly constant after an induction pe-
riod of 4 h. It seems that the RAFT agent has been oxidized
during the induction period, as indicated by the color change
from pink to light yellow, and the oxidation product causes
retardation effect on the polymerization rate. On this base,
we suggest that termination by oxidation of the living chains
may occur in normal RAFT polymerizations if the system is
not well deaerated.
tion of radicals and limited amount of air in that system.
Indeed, they have observed higher polydispersity and tailing
effect in GPC profile of the product prepared in the presence
of oxygen, which may be a consequence of oxidation termi-
nation during the polymerization. In the presence of AIBN,
however, remarkable retardation has been observed by Moad
et al. for the RAFT polymerization of MMA.80
CONCLUSIONS
RAFT agents and dithioester chain terminus are subject to
radical-induced oxidation by molecular oxygen. The reaction
converts efficiently dithioester moieties to thioester species.
The stability of thiocarbonylthio compounds toward oxida-
tion depends on both the structures of Z- and R-substituents.
Electron abstracting or bulky group in R-substituent leads to
decreased stability, whereas electron-donating group in Z-
substituent, such as in trithiocarbonates and xanthates, leads
to remarkably increased stability of the compounds. The
behavior correlates very well with the chain transfer ability
of the RAFT agents. The oxidation of thiocarbonythio moiety
Zhu and coworkers have observed rate-enhancement in
RAFT polymerizations of MMA and styrene in the presence
of oxygen.79 The results are not in contradictory to the pres-
ent work because of different reaction conditions and differ-
ent molecular structure of dithioesters. In ref. 79, no radical
initiator has been used, and the RAFT polymerization is initi-
ated by the thermal initiation of monomers, in which oxygen
plays the role of forming additional peroxide initiators, caus-
ing increase in polymerization rate. The oxidation of the
RAFT agent may occur at a slow rate due to low concentra-
FIGURE 10 GPC traces monitor-
ing the RAFT polymerizations of
styrene mediated by PEDB at 60
ꢂC in the absence (a) and pres-
ence (b) of air. Feed: styrene:
PEDB:AIBN
ratio).
¼
2000:1:1 (molar
1358
WILEYONLINELIBRARY.COM/JOURNAL/JPOLA

ARTICLE
19 Moad, G.; Chong, Y. K.; Postma, A.; Rizzardo, E.; Thang, S.
exhibits strong competitiveness over the RAFT process there-
fore is detrimental to the livingness of the polymerization.
Understanding the oxidation reaction is of help in obtaining
better control on the polymerization.
H. Polymer 2005, 46, 8458–8468.
20 Mayadunne, R. T. A.; Rizzardo, E.; Chiefari, J.; Krstina, J.;
Moad, G.; Postma, A.; Thang, S. H. Macromolecules 2000, 33,
243–245.
This work is subsidized by the National Science Foundation of
China (20574009).
21 Xu, J.; He, J.; Fan, D.; Wang, X.; Yang, Y. Macromolecules
2006, 39, 8616–8624.
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