International Journal of Organic Chemistry, 2011, 1, 148-157
doi:10.4236/ijoc.2011.14022 Published Online December 2011 (http://www.SciRP.org/journal/ijoc)
Poly Ethylene Glycols (PEG) and Micelles as Efficient
Catalysts for the Oxidation of Xanthine Derivatives under
Conventional and Non-Conventional Conditions
Somannagari Shylaja1, Kola Ramesh1, Pochampally Giridhar Reddy1, Kamatala Chinna Rajanna2*,
Pondichery Kuppuswamy Saiprakash2
1Department of Chemistry, Osmania University, Hyderabad, India
2Department of Chemistry, CBIT, Hyderabad, India
Received August 18, 2011; revise September 24, 2011; accepted October 9, 2011
Abstract
Oxidation of Xanthine alkaloid have been studied with various one and two electron oxidizing agents using
PEGs and micelle forming surfactants. The reaction is too sluggish in solution phase, but moderately fast in
presence of PEGs and micelles. However, the reactions are dramatically enhanced under microwave irradia-
tions. Present protocol has several advantages, such as solvent-free conditions, during work-up, fast reaction
times, high yields, eco-friendly operational and experimental simplicity, readily available additives as cata-
lysts.
Keywords: Oxidation, Xanthine Alkaloids, One and Two Electron Oxidizing Agents, Poly Ethylene Glycols
(PEG), Micelle Forming Surfactants, Catalysts, Microwave Irradiations
1. Introduction
Xanthine alkaloids (xanthines) are purine bases, found in
body tissues and fluids and in some plants. They are pro-
bably the most widely known and used alkaloids, being
constituents of popular daily beverages tea and coffee.
Xanthine alkaloids include: Caffeine, Theobromine, Pen-
toxifylline, Theophylline, Aminophylline, Dimenhydri-
nate, Dyphylline, 1-Methyl-3-isobutylxanthine, Xanthi-
nol Niacinate, Uri c A ci d , Xanthine.
Xanthine is an intermediate found in the degradation
of adenosine mono phosphate (AMP) to uric acid, being
formed by oxidation of hypoxanthine. Caffeine, theophyl-
line, and theobromine alkaloids are methylated xanthine
derivatives; they differ only in the number and position
of methyl substituents around the xanthine ring system.
Caffeine alkaloid is a central nervous system (CNS) sti-
mulant. It is also a diuretic and is used in combination
with analgesics. Theophylline and theobromine are minor
alkaloids of tea; theobromine also occurs in cocoa. Caf-
feine, theobromine, and theophylline and their deriva-
tives are used in medicine for their bronchodilator effects
[1]. Uric acid is an oxidation product of xanthine and
hypoxanthine, formed via xanthine oxidase enzyme; it is
the final oxidation product of catabolism of purines which
originate from food. A decrease in pH, as it occurs in
inflamed tissues, facilitates the formation of uric acid cry-
stals, which are the initial cause of gout. Furthermore,
xanthine is sparingly soluble in water, and metabolic ab-
normalities can occasionally lead to its precipitation as
aggregates, although xanthine “stones” are quite rare [2].
The N-methyl derivatives of xanthine (see Table 1), in-
cluding theophylline (3,7-dihydro-1,3-dimethyl-1H-purine-
2,6-dione), theobromine (3,7-dihydro-3,7-dimethyl-1H-pu-
rine-2,6-dione), and caffeine (3,7-dihydro-1,3,7-trim ethyl-
1H-purine-2,6-d ione), ar e alkaloids th at are widely distri-
buted in plant products and beverages and are known to
have many physiological effects, such as gastric acid se-
cretion, diuresis, and stimulation of the central nervous
system [3]. Besides, these compounds are considered to
be risk factors for asthma, kidney malfunction and car-
diovascular diseases [4].
Solvents play essential roles in ch emical processes not
only serving to put reactants into contact by dissolution
but also affecting rates, chemo-, regio- and stereo-selec-
tivity of the reactions. Until most recently, organic sol-
vents were the most common and perhaps the only choi-
ces of solvents among chemists. The most used organic
solvents comprise hydrocarbons (including halogenated
and aromatic hydrocarbons), ethers and alcohols. Despite
the usefulness and importance of these compounds in-

149 S. SHYLAJA ET AL.
Table 1. NMR and Mass Spectral data for selected reaction products.
Spectral data
Entry Substrates Product m/z 1H NMR
1 Caffeine 1,3,7-Try methyl uric acid 210δ 3.35(N-CH3); δ 3.41(N-CH3)
δ 3.73(N-CH3); δ 13.49(O-H)
2 Theobromine 3,7-Dimethyl uric acid 196δ 9.45(N-H); δ 3.24(N-CH3)
δ 3.73(N-CH3); δ 1 3.49(O-H)
3 Theophyllene 1,3-Dimethyl uric acid 196δ 3.35(N-CH3); δ 3.41(N-CH3)
δ 13.43(O-H); δ 13.92(N-H)
4 Xanthine Uric acid 168δ 13.91(N-H); δ 9.48( N-H)
δ 13.41(O-H); δ 15.53(N-H)
5 Hypoxanthine Uric acid 168δ 13.91(N-H); δ 9.48(N-H )
δ 13.41(O-H); δ 15.53(N-H)
organic reactions they undoubtedly have high flammabil-
ity and volatility, their hazardness and toxicity have a
detrimental impact on the environment. In recent past
this scenario has been substantially changed by environ-
mentally benign substitutes (green solvents) for volatile
and toxic organic solvents under the concepts of Green
Chemistry and green reaction processes [5,6]. Poly (eth-
ylene glycol) (PEG) [7-9], a biologically acceptable
polymer used extensively in drug delivery and in bio
conjugates as tools for diagnostics has been used as a
solvent medium support for various transformations. In
recent times PEG has surpassed even ionic liquids in
forefront of research PEG is economically cheap and
environmentally safe. To date some of the more impor-
tant reactions have been carried out and investigated in
PEG [7-23]. Besides the use of safer solvents, in recent
past increasing attention has also been paid for designing
eco friend- ly reactions using environmentally safe and
economically cheap reagents to prevent environmental
pollutions according to the guidelines given by Paul An-
astas and John Warner [5]. Recent reviews and publica-
tions [24-27] in the field of solvent-free organic synthesis
revealed that organic reactions performed under these
conditions are not only simple but also satisfy both eco-
nomical and environmental demands by replacing the
toxic solvents. Solvent free reactions further, have gained
much attention because of their enhanced selectivity,
mild reaction conditions, and associated ease of manipu-
lation. Apart from solvent free organic synthesis, quite
some attention has been paid to develop methodologies
using ultrasound and microwaves. Methods developed
under sonicated [28-33] and microwave irradiated condi-
tions [34-36] proved to good tools to save energy and
reduce reaction times to a greater extent. Considerable
efforts were also diverted to use economically cheap and
environmentally safe reagents as catalysts to design or-
ganic synthesis. A survey of literature reveals that Mi-
celles act as a kind of micro reactors and enhance the rate
and selectivity of a variety of chemical and biochemical
reactions. A close parallelism between enzymatic reac-
tions and micellar reactions has attracted the attention of
several synthetic organic chemists and biochemists [37-
40]. Far the past several years, our group has focused its
attention in designing synthetic protocols using a variety
of eco friendly materials such as micelle-forming surfac-
tants and unconventional energy sources (such as mi-
crowave irradiation and ultrasound) to enhance Vilsmei-
er-Haack (VH) and Hunsdiecker reactions [40-43]. Dr-
amatic rate accelerations followed by an increase in the
product yield were observed in all these reactions. En-
couraged by the striking features and applications of
PEGs, micelles, and microwave irradiation in chemical
processes and organic synthesis, coupled with zeal to
employ atom economy eco-friendly reagents, the author
proposes to take up Oxid ation of certain biologically im-
portant compounds such as xanthine (XAN), hypoxan-
thine (HXAN), caffeine (CAF), theophylline (TPL), theo-
bromine (TBR), using commonly available laboratory
desktop eco friendly reagents such as hydrogen peroxide
(H2O2), tetra butyl Hydrogen peroxide (TBHP), Potas-
sium peroxy disulfate (K2S2O8), Potassium peroxy di-
phosphate (K4P2O8), Sodium perborate (NaBO4), Potas-
sium periodate (KIO4), Pyridinium chloro chromate (PCC)
and Quinolonium chloro chromate (QCC). The proposed
work is taken up different stages 1) to conduct the reac-
tions under and microwav e conditions to save energy; 2)
to conduct the reactions in a mortar by grinding with a
pestle under solvent-free conditions or by using micro-
wave irradiation under solid phase conditi ons.
2. Experimental Details
2.1. Materials and Methods
All chemicals used were of analytical grade. Doubly dis-
tilled water (distilled over alkaline KMnO4 and acid di-
chromate in an all glass apparatus) was used whenever
required. Acetonitrile and other solv ents were HPLC gra-
de and used as such throug hout the work.

S. SHYLAJA ET AL.
150
Xanthine (XAN), hypoxanthine (HXAN), caffeine
(CAF), theophylline (TPL), theobromine (TBR), hydro-
gen peroxide(H2O2), tetra butyl Hydrogen peroxide (TB-
HP), Potassium peroxy disulfate (K2S2O8), Potassium
peroxy diphosphate (K4P2O8) and Sodium perborate (Na-
BO4), and Potassium periodate(KIO4), were procured from
Aldrich or E-Merck. Pyridinium chloro chromate (PCC)
and Quinolonium chloro chromate (QCC) were prepared
according the method of Corey as cited in literature [44].
2.2. Typical Experimental Procedure for
Oxidation of Xanthine Alkaloids
A neat mixture of xanthine alkaloid (1.0 mmol) dissolved
in acetonitrile and Reagent (1.2 mmol) were placed in a
50 ml R.B. flask and refluxed for several hours till the
reaction is completed as ascertained by TLC. After com-
pletion of the reaction, the contents were extracted with
dichlorom ethan e (2 - 25 ml) a nd wash ed with wat er (4 0 ml).
The reactions were too sluggish even under reflux condi-
tions. The dichloromethane layer was separated and dried
over MgSO4. After evaporation of the solvent, the res idue
was purified by flash column chromatography (SiO2, ethyl
acetate—hexane 1:2) to afford the end product. Main pro-
duct of oxidation was characterized as uric acid derivative
from IR, NMR and Mass spectroscopi c studies (Table 1).
2.3. Typical Experimental Procedure for PEG/
Micelle Mediated Oxidation of Xanthine
Alkaloids
A neat mixture of xanthine alkaloid (1.0 mmol) dissolved
in acetonitri le, PEG / micelle forming surfactant and Rea-
gent (1.2 mmol) were placed in a 50 ml R.B. flask and
refluxed for several hours till the reaction is completed as
ascertained by TLC. After completion of the reaction, the
contents were treated according the above procedure to
pure product of oxidation (Scheme 1). The reactions times
decreased in presen ce of PEG/ m icelles (Tables 2 to 5).
R1
R
R
N
O
O
N
N
N
R
R
R
N
N
N
N
R1
R
R
N
O
O
N
N
NOH
H
O
O
O
2
3
1
2
3
2
3
H
Uric acid derivatives)
Reagent / Reflux
(i)
(ii) Reagent / PEG/ Reflux
(iii) Reagent / Micelle / Reflux
(iv) Reagent / PEG / MWI
(v) Re a ge n t / M ice lle / M WI
Scheme 1. Reagent = H2O2, TBHP, K2S2O8, K4P2O8, KIO4,
NaBO4, PCC, QCC; Substrate = Xanthine, Hypoxanthine.
Caffeine, Theophylline, and Theobromine PEGs-PEG-200,
PEG-300, PEG-400 and PEG-600; Micelle-TX-100, SDS,
CTAB.
Table 2. Oxidation of caffeine and its related compounds in presence of TX-100 and various oxidizing agents.
Entry 1a 1b 1c 1d 1e
Substrate CAF TPL TBR HXAN XAN
(a) Under solution phase conditions
TBHP H2O2 K 2S2O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%)
1a 8.30 72 8.30 70 7.50 72 7.2070 7.5072 7.5070 8.20 70 8.3070
1b 8.30 72 8.30 70 7.50 72 7.2070 8.2070 7.5070 8.20 70 8.3070
1c 8.30 72 8.30 70 7.50 72 7.2070 8.2070 7.5070 8.30 69 8.3070
1d 9.00 70 9.00 68 8.20 70 8.0068 8.2070 8.2068 8.40 69 8.5068
1e 9.00 68 9.00 68 8.20 68 8.0065 8.3065 8.2065 8.40 68 8.5068
(b) Under microwave irradiation.
TBHP H2O2 K 2S2O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%)
1a 200 74 200 73 210 75 20078 21074 21074 220 70 21070
1b 210 72 210 70 210 72 21075 21070 21072 220 70 21070
1c 210 72 210 70 210 72 21075 21070 21072 220 70 21070
1d 240 69 250 68 220 70 24072 24068 24070 240 68 23068
1e 240 68 250 68 220 68 24070 24065 24068 240 65 23068

151 S. SHYLAJA ET AL.
Table 3. Oxidation of caffeine and its related compounds in presence of SDS and various oxidizing agents.
(a) Under solution phase conditions.
TBHP H2O2 K 2S2O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%)
1a 9.00 70 9.00 70 8.30 70 8.3070 8.4070 8.2070 8.40 70 9.0070
1b 9.00 70 9.15 70 8.30 70 8.3070 8.4070 8.3070 8.40 70 9.0070
1c 9.00 70 9.20 70 8.30 70 8.3070 8.5070 8.3070 8.40 69 9.0068
1d 9.15 70 9.30 68 8.40 68 8.4570 9.0070 8.5068 9.00 69 9.1068
1e 9.15 68 9.30 68 8.40 68 8.4569 9.0068 8.5065 9.00 68 9.1065
(b) Under microwave irradiation.
TBHP H2O2 K 2S2O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%)
1a 240 72 240 70 220 72 220 72 220 72 220 72 240 70 220 70
1b 240 72 240 70 220 72 220 72 220 70 220 70 240 70 220 70
1c 240 72 240 70 220 72 220 72 220 70 220 70 240 70 220 70
1d 270 69 270 69 240 70 260 70 250 68 260 69 260 68 240 68
1e 270 68 270 68 240 65 260 70 250 65 260 68 260 65 240 65
Table 4. Oxidation of Caffeine and its related compounds in presence of CTAB and various oxidizing agents.
(a) Under solution phase conditions.
TBHP H2O2 K 2S2O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%)
1a 9.30 72 9.20 70 9.00 72 9.0072 9.2073 9.1070 9.00 70 9.3070
1b 9.30 70 9.20 70 9.00 70 9.0070 9.2070 9.2070 9.10 68 9.3068
1c 9.30 70 9.20 70 9.00 70 9.0070 9.2070 9.2070 9.15 68 9.3068
1d 9.45 68 9.40 68 9.20 68 9.3070 9.3071 9.3065 9.30 68 9.4066
1e 9.45 68 9.40 68 9.20 65 9.3068 9.3068 9.3065 9.30 68 9.4064
(b) Under microwave irradiation.
TBHP H2O2 K 2S2O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%)
1a 270 70 270 70 240 72 240 72 260 70 260 70 270 70 240 70
1b 270 70 270 70 240 72 240 72 260 70 260 70 270 70 240 70
1c 270 70 270 70 240 72 240 72 260 70 260 70 270 70 240 70
1d 290 69 300 68 270 70 280 70 280 68 280 69 280 68 260 68
1e 290 68 300 68 270 68 280 68 280 65 280 65 280 65 260 68

S. SHYLAJA ET AL.
152
Table 5. Oxidation of caffeine and its related compounds in presence of PEG-300 and various oxidizing agents.
(a) Under solution phase conditions.
TBHP H2O2 K 2S2O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%)
1a 8.15 70 8.45 70 7.40 72 7.5072 7.4570 7.4572 8.00 70 8.0070
1b 8.15 70 8.45 70 7.40 72 7.5070 8.1570 7.4570 8.20 70 8.0070
1c 8.15 70 8.45 70 7.40 72 7.5070 8.1570 7.4570 8.20 69 8.0070
1d 9.00 68 9.30 68 8.30 70 8.2070 8.3068 8.3068 8.30 68 8.4568
1e 9.00 68 9.30 65 8.30 68 8.2070 8.3068 8.3068 8.30 65 8.4568
(b) Under microwave irradiation.
TBHP H2O2 K 2S2O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%)
1a 200 74 210 75 200 78 16080 20075 20075 200 73 20073
1b 200 70 210 70 200 72 16076 21072 20074 210 72 20072
1c 200 70 210 70 200 72 16075 21070 20072 200 72 21072
1d 240 68 250 65 220 68 18070 24068 22070 210 68 22068
1e 240 68 250 65 220 65 18068 24065 22068 220 65 22068
2.4. Typical Experimental Procedure for
Microwave Irradiated (MWI) Oxidation of
Xanthine Alkaloids
A neat mixture of xanthine alkaloid (1.0 mmol) dissolved
in acetonitrile, PEG/micelle forming surfactant and Re-
agent (1.2 mmol) were placed in a 50 ml R.B. flask. The
reaction mixture was inserted in a silica gel bath and
placed in a laboratory microwave oven and irradiated
(700 W) three times for three to five minutes with a pe-
riod of 20 seconds time intervals. After completion of the
reaction, the contents were treated according the above
procedure to pure product of oxidation (Scheme 1). The
reactions times decreased from several hours to few mi-
nutes under microwave irradiation in presence of PEG/
micelles (Tables 2-5).
3. Results & Discussion
Oxidation reactions with xanthine alkaloids were too
sluggish in acetonitrile media even under reflux condi-
tions with longer reaction times. However, micelle medi-
ated and PEG mediated reactions are underwent with
moderate progress, which could be seen from the data
presented in Table 2-5 and Figures 1-4. These data also
depict that nature of Oxidizing agent had significant ef-
fect on the rate of oxidation. Peroxide reagents are found
superior over other reagents while structural variation of
PEG had only a little influence on the rate of oxidation.
But when the reactions are conducted in micellar media
noticeable rate enhancements were noticed with TX-100
on par with PEG. However, anionic (SDS) and ca-
0
10
20
30
40
50
60
70
80
H2O2 TBHPPDSPDPSPBPCCQCCPPI
PEG 200 m edi at ed Caff i ene O xi dat i on
R. T (hrs )
Y i eld (%)
(a)
0
10
20
30
40
50
60
70
80
H2O2PCC PDPPDSPPIQCC SPBTBHP
MWI on PEG 200 mediated oxidation of Caffiene
R. T (mi n )
Yield (%)
(b)
Figure 1. PEG mediated caffeine oxidation with various
reagents. (a) Under solution phase; (b) Under Microwave
Irradiation.

153 S. SHYLAJA ET AL.
tionic (CTAB) micelle mediated reactions are relatively
less effect over TX-100 (Tables 2-4; Figures 3(a), 3(b)
4(a) and 4(b)). It is inter esting to not e that PEG (Table
5; Figures 1, 2(a) and 2(b)), and TX-100 probably be-
have in the same way because both of them have poly-
oxy ethylene moieties.
The efficient catalytic activity o f micelles could be at-
tributed to the fact micelles act as “ micro reactors” to fa-
cilitate the reactions through electrostatic/hydrophobic
interactions operating between reactive species [37-41].
The catalytic activity of PEGs could be explained in similar
lines to those of non-ionic micelles due to their structural
resemblance. Reaction times are reduced from several
hours (6 to 9 hr) to few minutes (6 to 9 minutes) between
reactions performed under standard oil-bath conditions
(heating under reflux) and microwave irradiations. The
observed dramatic rate enhancements under microwave
irradiations in the present study could be well explained
due to the formation of “molecular radiators” by direct
coupling of microwave energy to specific reagents in
homogeneous solution (microscopic hotspots) [45-47]
and by the elimination of wall effects caused by inverted
temperature gradients.
0
10
20
30
40
50
60
70
80
PEG200 PEG300PEG400 PEG600
Caffiene Oxidation with TBHP
R.T (hrs )
Yield (%)
(a)
0
10
20
30
40
50
60
70
80
PEG200 PEG300PEG400 PEG600
MWI Caffeine Oxidation by TBHP
R. T (m i n)
Y i el d (% )
(b)
Figure 2. Effect of structure of PEG on TBHP oxidation of
caffeine (a) Under solution phase; (b) Under microwave Ir-
radiation.
0
10
20
30
40
50
60
70
80
H2O2 TBHPPDSPDPSPBPCCQCCPPI
Tx medi at ed O x i dat i on of Caff iene
R. T (hrs)
Yield (%)
(a)
0
10
20
30
40
50
60
70
80
H2O2TBHPPDSPDPSPB PCCQCCPPI
MW I on TX100 mediat ed Caff i ene O xi dat i on
R. T (mi n)
Y i el d (% )
(b)
Figure 3. TX-100 mediated caffeine oxidation with various
reagents. (a) Under solution phase; (b) Under microwave ir-
radiation.
0
10
20
30
40
50
60
70
80
TX100 SDS CTAB
Mi cel l e m edi at ed TBHP oxidati on of Caff i ene
R. T (hrs)
Yield (%)
(a)
0
10
20
30
40
50
60
70
80
TX100 SDS CTAB
MWI on Micelle mediated TBHP Caffiene Oxidation
R. T (mi n)
Y iel d (%)
(b)
Figure 4. TBHP oxidation of caffeine under micellar condi-
tions. (a) Under micellar conditions in solution phase; (b)
Micellar effects under microwave irradiation.

S. SHYLAJA ET AL.
154
4. Conclusions
In summary, we have developed a simple and efficient me-
thod for oxidation of xanthine alkaloids using PEGs and
micelle forming surfactants. Xanthine alkaloid oxidation
is too sluggish in solution phase but moderately progres-
sed in presence of PEGs and micelles. However, the re-
actions are dramatically enhanced under microwave irra-
diations. Present protocol has several advantages, parti-
cularly solvent-free conditions, during work-up, fast re-
action times, high yields, eco-friendly operational and ex-
perimental simplicity, readily available additives as cata-
lysts.
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156
Electronic Supplementary Material
Elaborated data presented separately in Tables S1-S3 as
supplementary data depict the oxidation of various xan-
thine related compoun ds with d ifferent oxid izing ag - ents
in other PEG media.
Table S1. Oxidation of caffeine and its related compounds in presence of PEG-200 and various oxidizing agents.
Entry 1a 1b 1c 1d 1e
Substrate CAF TPL TBR HXAN XAN
(a) Under solution phase conditions.
TBHP H2O2 K 2S2O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%)
1a 8.00 72 8.30 70 7.30 74 7.3074 7.4573 7.3072 8.00 72 8.0070
1b 8.00 72 8.30 70 7.30 73 7.3072 8.0070 7.4570 8.00 70 8.0070
1c 8.00 72 8.30 70 7.30 72 7.3072 8.0070 7.4570 8.00 69 8.0070
1d 9.00 70 9.30 68 8.00 70 8.0068 8.2068 8.0068 8.30 68 8.4568
1e 9.00 68 9.30 68 8.00 68 8.0065 8.3068 8.0068 8.30 68 8.4568
(b) Under microwave irradiation.
TBHP H2O2 K 2S2O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%)
1a 180 75 200 75 180 78 150 80 180 75 180 75 200 73 200 73
1b 200 70 210 70 180 72 150 78 210 72 200 74 210 72 200 72
1c 200 70 210 70 180 72 150 78 180 70 180 72 200 72 210 72
1d 240 68 250 65 200 68 180 72 240 68 220 70 210 68 220 68
1e 240 65 250 65 200 65 180 70 240 65 220 68 220 65 220 68
Table S2. Oxidation of caffeine and its related compounds in presence of PEG-400 and various oxidizing agents.
(a) Under solution phase conditions.
TBHP H2O2 K 2S7O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%)
1a 8.30 70 8.45 70 8.00 72 8.0072 8.1570 8.0072 8.20 70 8.1570
1b 8.30 68 9.00 70 8.15 70 8.0070 8.3070 8.0070 8.30 69 8.2068
1c 8.30 68 9.00 70 8.15 70 8.0070 8.3070 8.0070 8.30 69 8.2068
1d 9.30 68 9.30 68 8.30 70 8.3069 8.3068 8.0068 8.30 68 8.4568
1e 9.30 68 9.30 65 8.30 68 8.3068 8.3068 8.3068 8.30 65 8.4568
(b) Under microwave irradiation.
TBHP H2O2 K 2S2O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%)
1a 210 73 220 75 210 78 180 78 210 74 210 73 210 70 210 72
1b 210 70 220 70 210 72 180 75 210 72 200 72 210 68 220 70
1c 210 70 220 70 210 72 180 74 210 70 200 70 210 68 210 70
1d 260 68 250 65 240 65 200 68 240 65 220 70 220 68 220 68
1e 260 68 250 65 240 65 200 65 240 65 220 68 220 65 220 65

157 S. SHYLAJA ET AL.
Table S3. Oxidation of caffeine and its related compounds in presence of PEG-600 and various oxidizing agents.
(a) Under solution phase conditions.
TBHP H2O2 K 2S2O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%) RT (hrs) Yield (%)
1a 8.45 70 9.00 70 8.20 72 8.2072 8.3070 8.2072 8.30 70 8.3070
1b 8.45 68 9.20 70 8.30 70 8.2070 8.4570 8.2070 8.30 69 8.3068
1c 8.45 68 9.20 70 8.30 70 8.2070 8.4570 8.2070 8.30 69 8.3068
1d 9.45 68 9.40 68 8.45 70 8.4069 8.4568 8.4068 8.40 68 8.4568
1e 9.45 68 9.40 65 8.45 68 8.4068 8.4568 8.4068 8.40 65 8.4568
(b) Under microwave irradiation.
TBHP H2O2 K 2S2O8 K 4P2O8 PCC QCC NaBO4 KIO4
ENTRY RT
(sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%) RT (sec) Yield (%)
1a 240 70 240 72 220 75 200 74 220 74 220 72 220 70 210 70
1b 240 70 250 68 220 70 200 72 220 70 220 70 220 68 220 70
1c 240 70 250 68 220 70 200 72 220 70 220 70 220 68 220 70
1d 280 68 280 65 260 65 220 68 250 65 220 68 240 68 220 68
1e 280 68 280 65 260 65 220 65 250 65 220 68 240 65 220 68