Calix[n] arenes mediated phase-transfer catalytic synthesis of purine derivatives

Article abstract of DOI:10.1002/kin.20394

A new route was designed to achieve the synthesis of purine derivatives under phase-transfer catalysis conditions using calix[n]arenes TAC_nA (n = 4, 6, and 8) as phase-transfer catalyst for the first time in this particular type of synthesis. The compounds were synthesized in excellent yields (70%-80%) and the structures were established on the basis of consistent IR, ¹H NMR, FAB-Mass, and elemental analyses data. Their purity has been ascertained by chromatographic resolution using acetonitrile, methanol, and water (50:30:20, v/v) as eluenting system. Moreover, the kinetics of the reaction was studied and it was found to obey first-order kinetics. Effect of various parameters, namely, temperature, amount of catalyst, stirring speed, and so on was also investigated.

Full text of DOI:10.1002/kin.20394

Calix[n]arenes Mediated
Phase-Transfer Catalytic
Synthesis of Purine
Derivatives
PRATIBHA SHARMA, ASHOK KUMAR, VINITA SAHU, JITENDRA SINGH
School of Chemical Sciences, Devi Ahilya University, Takshashila Campus, Indore, MP 452 001, India
Received 10 June 2008; revised 10 September 2008; accepted 19 September 2008
DOI 10.1002/kin.20394
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: A new route was designed to achieve the synthesis of purine derivatives under
phase-transfer catalysis conditions using calix[n]arenes TACnA (n = 4, 6, and 8) as phase-
transfer catalyst for the first time in this particular type of synthesis. The compounds were
synthesized in excellent yields (70%–80%) and the structures were established on the basis
of consistent IR, 1H NMR, FAB-Mass, and elemental analyses data. Their purity has been
ascertained by chromatographic resolution using acetonitrile, methanol, and water (50:30:20,
v/v) as eluenting system. Moreover, the kinetics of the reaction was studied and it was found to
obey first-order kinetics. Effect of various parameters, namely, temperature, amount of catalyst,
stirring speed, and so on was also investigated. ꢀ 2008 Wiley Periodicals, Inc. Int J Chem Kinet
C
41: 265–274, 2009
expensive reagents [1–3]. PTC is considered to have a
great potential for industrial scale applications too. Or-
ganic chemists and chemical engineers have been ex-
ploiting PTC by virtue to enhance productivity, quality,
safety, vis-a`-vis from the viewpoint of environmental
considerations.
A number of phase-transfer catalysts are being de-
veloped to combat the requirement of synthetic chem-
istry applications [4]. In this context, the potential of
calix[n]arenes in phase-transfer catalyst mediated syn-
thesis is yet to be explored. Currently, the chemistry
of calix[n]arenes is growing at a very fast rate and
has received increasing attention due to their utiliza-
tion in supramolecular chemistry. Most of the time,
calix[n]arenes were reported to promote host–guest in-
teractions in the solvent extraction processes. Investi-
gations are continuously going on to explore the utility
of this wonderful system in many disciplines of science
[5,6].
INTRODUCTION
Interaction between two substances located in differ-
ent phases of a mixture is often inhibited because of
the inability of reagents to come together. Tradition-
ally, this problem is solved by the use of an appropriate
mutual solvent. An alternative solution to the hetero-
geneity problem is the introduction of phase-transfer
catalysts. The term phase-transfer catalysis (PTC)
encompasses several effective techniques of which
typical advantages are simplicity, mild conditions,
high-reaction rates, high selectivities, and the use of in-
Correspondence to: Pratibha Sharma; e-mail: drpratibhasharma@
yahoo.com.
Contract grant sponsor: Department of Science & Technology,
Govt. of India, New Delhi.
Contract grant number: SR/S-1/IC-17/2006.
2008 Wiley Periodicals, Inc.
c
ꢀ

266
SHARMA ET AL.
antineoplastic [11,12], antibiotic [13], and antitubercu-
lar [14] agents. Moreover, these compounds have found
wide application as adenosine receptor ligands [15,16],
antiparasitic agents [17], cyclin-dependent kinase in-
hibitors [18], antitumor [19], and antiviral compounds
[20].
N
+
O
N (CH )
3 3
H3C
O
N
H
N
CH
2
OMe
N
n
CH3
R
N
H3C
A systematic perusal of literature survey reveals
that a number of synthetic routes are available for the
construction of substituted purine nucleus deriving
from amidines or guanidines with retrosynthetic
disconnection at the ring fusion [21], inverse electron
demand Diels–Alder cycloaddition (IEDDAC) reac-
tion [22], metal-catalyzed cross-coupling reactions
[23], SNAr displacement in anilines and amines fol-
lowed by N-alkylation and N-arylation [24]. However,
the methods reported so far are tedious with low out-
come of the overall yields. Thus in continuation of our
work on heterocyclic compounds [25–30] and in quest
of developing a synthetic strategy under phase-transfer
catalytic condition, a novel route has been designed to
obtain 7-[4ꢁ-(3ꢁ-methylisoxazolyl-5ꢁ(4ꢁH)-one)-8-(2ꢁ-
methylprop-1ꢁ-en-1ꢁ-yl)-7H-purine derivatives 8a–c.
The synthesis of designed purine derivatives was
achieved by the insertion of a reactive intermediate,
namely, dimethylvinylidine carbene (generated in situ,
Scheme 1) into the N N moiety of substituted
3-methyl-4-[(E)-pyrimidin-4-yldiazenyl]isoxazol-
5(4H)-one 4a–c successively followed by cyclization
and rearrangement yields appropriately substi-
tuted 7-[4ꢁ-(3ꢁ-methylisoxazolyl-5ꢁ(4ꢁH)-one)-8-(2ꢁ-
methylprop-1ꢁ-en-1ꢁ-yl)-7H-purines 8a–c.
1a
1b
Figure 1 (1a) Structure of calix[n]arene TACnA (n = 4, 6,
and 8) and (1b) structure of synthesized purines (R = H, Cl,
OH).
Some functionalized calix[n]arenes were also de-
veloped as new phase-transfer agents for normal
PTC reactions, namely, in Aldol-type condensa-
tion and Michael addition reactions in water [7,8].
Calix[4]arene based multisite phase-transfer catalysts
exhibited significant high-catalytic activity as com-
pared to single-site phase-transfer catalysts in Darzens
condensation, O/N-alkylation reactions and ethyl ben-
zene oxidation [9]. The water-soluble calix[n]arenes
act as efficient inverse phase-transfer catalysts in the
nucleophilic substitution reaction of alkyl and arylalkyl
halides with nucleophiles in water [10]. Water-soluble
calix[n]arene catalytic system provides additional op-
tions in the field of biphasic catalysis for synthetic
chemistry and process engineering. Hence, keeping in
view such considerations, we have explored the poten-
tial of supramolecular calix[n]arenes 1a as the effec-
tive PTC to synthesize potentially significant purine
systems 1b (Fig. 1).
Purine derivatives are of great importance in
biomedical sciences. These are used in the regulation of
many biological processes and as constituents of DNA
and RNA. Purines, purine nucleosides, and nucleotides
participate in the signal transduction and regulation of
many biological processes in cells and tissues as lig-
ands of receptors and as second messengers (c-AMP).
The interest in modified purine derivatives is immense
as pharmacophoric entities. For instance, purine bases
and their nucleosides constitute an important group of
EXPERIMENTAL METHODS
All the chemicals, namely, potassium hydroxide, ben-
zene, ethanol, and other reagents used were of AR
grade purity. Calix[n]arenes TACnA (n = 4, 6, and 8)
were prepared as per the literature procedure [31,32].
All the synthesized compounds were identified by IR
1H NMR and FAB Mass spectroscopy as well as ele-
mental analysis. Melting points were determined on an
electrothermal apparatus by open capillary method and
H C
3
CH
CH3
3
aq. KOH
conc.HCl,CaCl2
C
C
H C
C
CH
3
H3C
C
CH
Stirring, 30 min
H C
3
Cl
OH
(5)
(6)
Scheme 1
International Journal of Chemical Kinetics DOI 10.1002/kin

PHASE-TRANSFER CATALYTIC SYNTHESIS OF PURINE DERIVATIVES
267
1
are uncorrected. The H NMR spectra were recorded
In a 250-mL round-bottomed flask, an equimo-
lar quantity of 1-ethoxy-2-pyrimidinylazo butane-1,3-
dione 3a–c and hydroxylamine hydrochloride were
taken together in ethyl alcohol (25 mL) and allowed
to undergo refluxation for 3-4 h at 80◦C to obtain crys-
tals of required 3-methyl-4-[(E)-(5-methylpyridin-2-
yl)diazenyl]isoxazol-5(4H)-one 4a–c in good yield
(70%–75%). An overview of systematic method-
ology of schematic pathway is depicted in
Scheme 2.
on a Bruker DRX300 instrument (300 MHz) in CDCl3
using TMS as an internal standard. Chemical shifts
are reported in δ units (ppm) values. All IR spectra
were run on a Shimadzu 460 spectrophotometer in
KBr Discs; frequencies are reported in cm−1. FAB
mass spectra (FAB MS) were recorded on a JEOL SX
102 Mass Spectrometer. To ascertained the purity of all
the synthesized compounds, analytical thin layer chro-
matography was performed on E Merck silica gel G
(0.50 mm, plate no. 5700) using acetonitrile, methanol,
and water (50:30:20, v/v) as eluent. Elemental analyses
were performed on an Elementar Vario EL-III Carlo-
Erba-1108 equipment.
Preparation of 7-[4ꢀ-(3ꢀ-Methylisoxazolyl-
5ꢀ(4ꢀH)-one)-8-(2ꢀ-methylprop-1ꢀ-en-1ꢀ-yl)-
7H-purine 8a–c
Preparation of 3-Methyl-4-[(E)-(5-methyl-
pyridin-2-yl)diazenyl]isoxazol-5(4H)-one
4a-c
In a 250-mL three-necked flask fitted with drop-
ping funnel and a mechanical stirrer, a mixture
of 50% aq. KOH (25 mL), TACnA as PTC (1.0
mmol), and benzene (5 mL) was taken and stirred for
30 min. To this, 3-methyl-4-[(E)-(5-methylpyridin-2-
yl)diazenyl]isoxazol-5(4H)-one 4a–c (10 mmol) was
added slowly and stirred for further 5–7 h under ni-
trogen atmosphere. 3-Chloro-3-methyl-1-butyne (25
mmol) in benzene (5 mL) was added slowly to the
mixturewithcontinuous stirring. Contents werediluted
with water (125 mL), followed by extraction twice with
ether to afford crude product, which was then purified
on an alumina column. Solid crystals of 1-isoxazolyl-
2-[2ꢁ-methyl-prop-1-en-1-yl] imidazo[4,5-b] pyridine
8a–c were then obtained in good yield. An overview
of synthetic pathway is depicted in Scheme 3.
In a 250-mL round-bottomed flask, solution of 4-
aminopyrimidine 1a–c (10 mmol) in concentrated hy-
drochloric acid (4.0 mL) and distilled water (4.0 mL)
was taken. To this aqueous solution of sodium nitrite
(0.69 g, 10 mmol) was added dropwise within 10–15
min at 0–5◦C. Meanwhile, ethyl acetoacetate (1.30 g,
10 mmol), sodium acetate (0.82 g, 10 mmol), and ethyl
alcohol (20 mL) were taken in another beaker at 0◦C.
Now, the diazotized solution was added dropwise to
this solution under temperature-controlled conditions.
The crystals of 1-ethoxy-2-pyrimidinylazo butane -1,3-
dione 3a–c thus obtained were filtered, washed with
water, and dried.
COOEt
H C
O
O
3
H C
2
N
NH2
+
-
COCH
N X
3
NaNO2 / HCl
0–5 C
N
O
N
Et
N
N
N
N
CH3COONa,
C2H5OH
N
N
R
R
R
(3a–c)
(1a–c)
(2a–c)
C2H5OH
Reflux for 4 h
.
NH2OH HCl
R
H
1a
H3C
N
1b Cl
1c OH
N
O
N
N
N
O
R
(4a–c)
Scheme 2
International Journal of Chemical Kinetics DOI 10.1002/kin

268
SHARMA ET AL.
H3C
N
N
O
H3C
O
N
C
C
:
+
N
N
H3C
R
(4a–c)
(6)
aq. KOH
TACnA(PTC)
+
N
(CH )
3 3
Entry
R
4a
H
where TACnA =
CH
N
2
OMe
H3C
N
n
O
O
4b Cl
4c OH
N
N
R
N
C
CH3
H3C
(7a–c)
N
O
H3C
H C
3
N
N
O
H
C
O
N
R
N
N
N
N
C
CH3
CH3
O
C
N
R
N
C
CH
3
CH
3
(8a–c)
H3C
N
N
O
N
C
N
~H
N
R
C
O
N
N
O
O
H3C CH3
H3C
H3C
O
O
~H
(11a–c)
N
N
N
N
C
C
C
C
CH3
CH3
CH3
N
N
H
R
N
R
N
CH3
(10a–c)
(9a–c)
Scheme 3
International Journal of Chemical Kinetics DOI 10.1002/kin

PHASE-TRANSFER CATALYTIC SYNTHESIS OF PURINE DERIVATIVES
269
Synthesis of 7-[4ꢀ-(3ꢀ-Methylisoxazolyl-
5ꢀ(4ꢀH)-one)-8-(2ꢀ-methylprop-1ꢀ-en-1ꢀ-yl)-
7H-purine 8a
H4), 10.31 (s, 1H, OH); FAB-MS m/z 287; Anal.
Calcd for C13H13N5O3: C, 54.35; H, 4.56; N, 24.38.
Found: C, 54.34; H, 4.56; N, 24.36.
mp (◦C) 126–127; Yield: 76%; IR (KBr) (cm−1): 3011
( C H, sp2), 2987 (C H, sp3), 1738 (C O), 1629
(C C/C N), 1451, 1365 (C H, bending, sp3), 1061
REACTION MECHANISM AND KINETIC
MODEL
1
(C O), 1047 (C N); H NMR (δ ppm): 2.51 (s, 6H,
CH3), 2.83 (s, 3H, CH3), 3.02 (s, 1H, CH-CO ),
4.34 (s, 1H, CH ), 7.41 (s, 1H, CH, H4), 7.53 (s,
1H, CH, H2); FAB-MS m/z 271; Anal. Calcd for
C13H13N5O2: C, 57.56; H, 4.83; N, 25.82. Found: C,
57.51; H, 4.81; N, 25.79.
Kinetic Measurement
For kinetic measurement a 100-mL three-necked flask
was used consisting of an agitating device and inlets
for thermometer and samples. The reaction aliquots
were prepared in volumetric flasks. Reactor was im-
mersed in an isothermal water bath and charged with
required quantity of 3-methyl-4-[(E)-pyrimidin-4-
yldiazenyl]isoxazol-5(4H)-one (4a), 50% KOH, PTC
in benzene. Stirring was started and organic layer was
extracted at regular intervals of time by stopping the
stirring intermittently to allow the adequate separation.
Each time five samples were taken and completion of
reaction was monitored by TLC and HPLC (Fig. 2).
Synthesis of 2-Chloro-7-[4ꢀ-(3ꢀ-Methyl-
isoxazolyl-5ꢀ(4ꢀH)-one)-8-(2ꢀ-methylprop-1ꢀ-
en-1ꢀ-yl)-7H-purine 8b
mp (◦C) 119–120; Yield: 75%; IR (KBr) (cm−1): 3019
( C H, sp2), 2980 (C H, sp3), 1743 (C O), 1635
(C C/C N), 1458, 1370 (C H, bending, sp3), 1069
1
(C O), 1050 (C N); H NMR (δ ppm): 2.62 (s, 6H,
CH3), 2.93 (s, 3H, CH3), 3.22 (s, 1H, CH), 4.54
(s, 1H, CH ), 7.48 (s, 1H, CH, H4); FAB-MS m/z
306; Anal. Calcd for C13H12ClN5O2: C, 51.07; H, 3.96;
N, 22.91. Found: C, 51.05; H, 3.93; N, 22.89.
Model for Kinetic Reaction Mechanism
The formation of 7-[4ꢁ-(3ꢁ-methylisoxazolyl-5ꢁ(4ꢁH)-
one)-8-(2ꢁ-methylprop-1ꢁ-en-1ꢁ-yl)-7H-purine 8a–c
can be expressed as
Synthesis of 2-Hydroxy-7-[4ꢀ-(3ꢀ-methyl-
isoxazolyl-5ꢀ(4ꢀH)-one)-8-(2ꢀ-methylprop-1ꢀ-
en-1ꢀ-yl)-7H-purine 8c
mp (◦C) 130–131; Yield: 78%; IR (KBr) (cm−1) 3548
( OH str.), 3025 ( C H, sp2), 2984 (C H, sp3), 1739
(C O), 1624 (C C/C N), 1456, 1363 (C H, bend-
ing, sp3), 1068 (C O), 1051 (C N); 1H NMR (δ ppm):
2.53 (s, 6H, CH3), 2.83 (s, 3H, CH3), 3.04 (s, 1H,
CH CO ), 4.34 (s, 1H, CH ), 7.41 (s, 1H, CH,
k
C8H7N5O2 + :C=C=C(CH3)2 −−−→ C13H13N5O2 (org)
(1)
From (1) the change rate of the reaction is expressed
as
−d
[C8H7N5O2] =
dt
k[C8H7N5O2]o[:C=C=C(CH3)2]o
(2)
C5H6Cl-K+ + H2O
C5H7Cl + KOH (aq)
Inorganic phase
-
+
-
TACnAn+ nC5H6Cl + nK X
-
nC5H6Cl-K+ + TACnAn+Xn
.
Interfacial region
-
n :C=C=C(CH3)2 + TACnAn+Cln
-
+ -
TACnAn+ nC5H6Cl + nK X
.
Organic phase
C8H7N5O2 +:C=C=C(CH3)2
C13H13N5O2 +(org)
Figure 2 An overview of interfacial reaction mechanism.
International Journal of Chemical Kinetics DOI 10.1002/kin

270
SHARMA ET AL.
where the concentration of dimethylvinylidene carbene
was kept constant; Eq. (2) can now become
ous solution resulting no reaction with 3-methyl-
4-[(E)-pyrimidin-4-yl diazenyl]isoxazol-5(4H)-one
4a. However, the addition of small amount
of TACnA changes the scenario dramatically
and the 7-[4ꢁ-(3ꢁ-methylisoxazolyl-5ꢁ(4ꢁH)-one)-8-(2ꢁ-
methylprop-1ꢁ-en-1ꢁ-yl)-7H-purine 8a was isolated in
good yields. The reaction catalyzed by TACnA has
taken place predominantly in bulk organic phase and/or
at benzene–water interface.
−d
[C8H7N5O2] = kapp[C8H7N5O2]o
kapp = k[:C=C=C(CH3)2]o
(3)
(4)
dt
Therefore, the reaction of dimethylvinylidene carbene
and C8H7N5O2 is irreversible and can be expressed as
follows:
kapp
[C8H7N5O2] −−−→ [C13H13N5O2]o
(5)
Effect of Catalyst
The influence of the catalyst concentration in aqueous
solution upon the initial reaction rate is shown in Fig. 3.
The catalytic activities of TACnA increase in the order
of TAC4A < TAC6A < TAC8A. It is assumed that
these differences are attributable to their cavity sizes.
The reaction follows pseudo-first-order reaction rate
kinetics.
As shown in Eq. (5), the change rate of these compo-
nents is
−d
[C8H7N5O2] = −kapp[C8H7N5O2]o
(6)
dt
Eq. (6) can be integrated as
[C8H7N5O2]o
ln
= −kapp
t
(7)
(8)
(9)
[C8H7N5O2]o,i
Effect of Amount of Catalyst
or
The effect of amount of catalyst was studied by varying
the amount of catalyst from 0.5 to 2.5 mmol. As shown
in Fig. 4, the rate constant continuously increases as
the amount of catalyst was increased. The rate of reac-
tion was directly proportional to the catalyst amounts.
A graph of the pseudo-first-order rate constant versus
the amount of catalyst (Fig. 4) suggested that the rate
of reaction is linearly dependent on the amount of cat-
alyst. The increase in rate was observed owing to the
increase in number of active sites for the interaction
at the benzene–water interface. The large cavity size
in the calix[n]arenes system provides stabilization of
3-chloro-3-methyl-1-butyne at the benzene–water in-
terface and increases the probability of interaction.
[C8H7N5O2]o = [C8H7N5O2]o,ie−k
app t
The conversion of C13H13N5O2 is defined as
[C8H7N5O2]o
(1 − x) =
[C8H7N5O2]o,i
Eq. (8) can be modified as
−ln(1 − x) = kapp t
(10)
RESULTS AND DISCUSSION
The reaction of 3-methyl-4-[(E)-pyrimidin-4-yl
diazenyl]isoxazol-5(4H)-one 4a with 3-chloro-3-
methyl-1-butyne 5 in the presence of aqueous potas-
sium hydroxide and catalytic amount of TACnA
(PTC) was carried out. The pseudo-first-order re-
action conditions were maintained upon taking into
consideration excess amount of 3-chloro-3-methyl-
1-butyne and aqueous potassium hydroxide. It was
noticed that, in the absence of phase-transfer cat-
alyst, no final product was isolated by the reac-
tion of 3-chloro-3-methyl-1-butyne 5 with 3-methyl-4-
[(E)-pyrimidin-4-yldiazenyl]isoxazol-5(4H)-one 4a
for 2.5 h. The reason was that 3-chloro-3-methyl-
1-butyne could be easily hydrolyzed in aque-
Effect of Amount of Substrate
Effect of amount of substrate was investigated by vary-
ing the substrate concentration from 5 to 25 mmol
and keeping constant all other parameters. The effect
of amount of substrate is shown in Fig. 5. The ob-
served pseudo-first-order rate constant decreases as the
amount of the substrate increases. These results suggest
that the concentration of the substrate in organic phase
is not important and that at the interface may be vi-
tal. The kinetics is not simple with respect to substrate
in the reaction in which the interfacial mechanism is
operative.
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PHASE-TRANSFER CATALYTIC SYNTHESIS OF PURINE DERIVATIVES
271
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
TAC4A
TAC6A
TAC8A
0
10
20
30
40
50
60
Time (min)
Figure 3 A plot of −ln(1 − x) versus time for different catalysts: 10 mmol of 3-methyl-4-[(E)-pyrimidin-4-yldiazenyl]isoxazol-
5(4H)-one 4a, 1.0 mmol catalyst, 10 mL of 50% of KOH, 20◦C temp, stirring speed = 800 rpm.
2.5
0.5 mmol
1.0 mmol
1.5 mmol
2.0 mmol
2.5 mmol
2.0
3.0 mmol
1.5
1.0
0.5
0.0
0
10
20
30
40
50
60
70
Time (min)
Figure 4 Effect of amount of TAC4A on the synthesis of 7-[4ꢁ-(3ꢁ-methylisoxazolyl-5ꢁ(4ꢁH)-one)-8-(2ꢁ-methylprop-1ꢁ-en-1ꢁ-
yl)-7H-purine 8a: 10 mmol of 3-methyl-4-[(E)-pyrimidin-4-yldiazenyl]isoxazol-5(4H)-one 4a, 10 mL of 50% of KOH, 20◦C
temp, stirring speed = 800 rpm.
Effect of Temperature
the range of 20–40◦C when the reaction con-
Temperature is an important factor in affecting the
reaction rate, because side reactions could be in-
duced at a temperature higher than 50◦C. The ef-
fect of temperature on the rate was studied in
ditions were 10 mmol 3-methyl-4-[(E)-pyrimidin-
4-yldiazenyl]isoxazol-5(4H)-one 4a, 1.0 mmol of
TAC4A, 10 mL of 50% of KOH, and 800 rpm
stirring speed. Evidence of irreversibility and
International Journal of Chemical Kinetics DOI 10.1002/kin

272
SHARMA ET AL.
2.5
2.0
1.5
1.0
0.5
0.0
5 mmol
10 mmol
15 mmol
20 mmol
25 mmol
0
10
20
30
40
50
60
Time (min)
Figure 5 Effect of amount of 3-methyl-4-[(E)-pyrimidin-4-yl diazenyl]isoxazol-5(4H)-one 4a on the synthesis of 7-[4ꢁ-(3ꢁ-
methylisoxazolyl-5ꢁ(4ꢁH)-one)-8-(2ꢁ-methylprop-1ꢁ-en-1ꢁ-yl)-7H-purine 8a: 1.0 mmol of TAC4A, 10 mL of 50% of KOH, 20◦C
temp, stirring speed = 800 rpm.
7
20 C
6
25 C
30 C
35 C
5
40 C
4
3
2
1
0
0
10
20
30
40
50
60
Time (min)
Figure 6 Effect of temperature on the synthesis of 7-[4ꢁ-(3ꢁ-methylisoxazolyl-5ꢁ(4ꢁH)-one)-8-(2ꢁ-methylprop-1ꢁ-en-1ꢁ-yl)-
7H-purine 8a: 10 mmol of 3-methyl-4-[(E)-pyrimidin-4-yl-diazenyl]isoxazol-5(4H)-one 4a, 1.0 mmol of TAC4A, 10 mL of
50% of KOH, stirring speed = 800 rpm.
pseudo-first-order kinetics was shown in Fig. 6. The
plot of −ln(1 − ×) versus time for all of temperatures
resulted a straight line. These results also justify the use
of Eq. (11) to calculate the constant kapp. From Fig. 6
it was also found that the reaction rate is increased
with an increase in the temperature. The reason was
International Journal of Chemical Kinetics DOI 10.1002/kin

PHASE-TRANSFER CATALYTIC SYNTHESIS OF PURINE DERIVATIVES
273
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
100 rpm
250 rpm
400 rpm
800 rpm
1500 rpm
0
10
20
30
40
50
60
70
Time (min)
Figure 7 Effect of stirring speed on the synthesis of 7-[4ꢁ-(3ꢁ-methylisoxazolyl-5ꢁ(4ꢁH)-one)-8-(2ꢁ-methylprop-1ꢁ-en-1ꢁ-yl)-
7H-purine 8a: 10 mmol of 3-methyl-4-[(E)-pyrimidin-4-yldiazenyl]isoxazol-5(4H)-one 4a, 1.0 mmol of TAC4A, 10 mL of
50% of KOH, 20◦C temp.
that the energy of reactant molecules is higher and the
collision between the molecules is also increased at a
higher temperature.
role in PTC processes due to greater van der Waal in-
teractions and large cavity size (surface area) to fit the
interacting molecule, which results in stabilization of
interacting molecules and an increase in the rate of
reaction.
Effect of Stirring Speed
The mass transfer between two phases is an important
factor in affecting the rate of reaction. In this work
the solution is agitated to enhance the mass transfer of
component between two phases. Figure 7 shows the
effect of various stirring speeds on the reaction rate.
Below 800 rpm, the reaction was highly affected by
the stirring speed in which the mass transfer plays an
important role. It was increased with an increase in the
stirring speed up to 800 rpm. A further increase in the
stirring speed shows no significant change in the rate
of reaction. The reaction was insensitive to the stirring
speed more than 800 rpm.
We are grateful to the Central Drug Research Institute,
Lucknow, India, for providing spectroanalytical facilities.
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