9
870 Kotaiah et al.
Asian J. Chem.
Alkylating agent/ Physical grinding/
CO / RT/ 5-10 mins
In PEG-600: A mixture of 1 (1.42 g, 10 mM), alkylating
agent (10 mM) and PEG-600 (20 mL) was stirred at RT for
h. At the end of this period, the mixture was poured into
K
2
3
2
ice-cold water (50 mL). The separated solid was filtered,
washed with water (2 × 10 mL) and dried. The crude product
was recrystallized from ethanol to obtain pure 2(a-c). For
yields, please see Table-1.
OH
OH
N
N
Alkylating agent/
H
3
C
N
SH
R
S
H
3
C
N
(1)
(
2 a-c)
2 3
Ethanol/ K CO / RT/ 2 hrs
Under microwave irradiating conditions: Mixture of
1
(1.42 g, 10 mM) and alkylating agent (10 mM) was taken in
Alkylating agent/
a 10 mL CEM-reaction tube sealed by rubber stopper and
subjected to microwave irradiation for 5 min at 130ºC in the
commercial micro-wave reactor.After that, the tube was cooled
and the completion of reaction was checked by TLC. Then,
the mixture was poured into ice-cold water (2 × 20 mL). The
separated solid was filtered, washed with water (2 × 10 mL)
and dried. The crude product was recrystallized from ethanol
to obtain pure 2(a-c). For yields please see Table-1.
PEG-600/ RT/ 2 hrs
Alkylating agent/
Microwave irradiation
4
50 W / 5 mins
2a, R= -CH
b, R=-CH
2c, R=Ph-CH
3
2
2
-CH
3
2
Alternate synthesis of 2a-b
O
OH
OEt
HN
N
EtOH/ KOH
N
S
R
H
2
RESULTS AND DISCUSSION
H C
3
O
Reflux/ 3 hrs H C
3
R
S
N
HSO
4
3
(2 a-b )
Reaction of 1 with each of the alkylating agents, like
dimethyl sulphate (DMS), diethyl sulphate (DES) and benzyl
2
a, R= -CH
3
2 3
2b, R=-CH -CH
chloride (PhCH
2
Cl), in the presence of K
2
CO as a mild base,
3
Alternate synthesis of 2c
by a simple physical grinding of the reaction mixture in a
mortar and pestle under solvent-free conditions for 10-15 min
at room temperature, followed by processing, gave, respec-
tively 6-methyl-2-(methylthio)pyrimidin-4(3H)-one (2a, i.e.,
O
OH
OEt
HN
EtOH/ KOH
N
S
R
2
H N
H
3
C
O
Reflux/ 3 hrs
R
S
H
3
C
N
HCl
5
3
(
2 c )
R = CH
R = C
2c, i.e., R = PhCH
3
), 6-methyl-2-(ethylthio)pyrimidin-4(3H)-one (2b, i.e.,
) and 6-methyl-2-(benzylthio)pyrimidin-4(3H)-one
Cl), as the products identical with the one
2
H
5
2c, R=Ph-CH
2
OH
OH
(
2
N
RT /1-2 h
6-9
N
reported in the earlier methods in all respects (m.p. m.m.p
and co-tlc analysis).
H
3
C
N
SH
H
3
C
N
SH
The reaction was also carried out in ethanol as a solvent.
Thus, treatment of 1, independently, with each of dimethyl
sulphate (DMS), diethyl sulphate (DES) and benzyl chloride
(
PhCH
presence of K
gave, respectively, 2a (i.e., 2, R = CH
and 2c (i.e., 2, R = PhCH ) identical with the same products
2
Cl) in ethanol at room temperature for 2 h in the
CO as a base, followed by simple processing,
), 2b (i.e., 2, R = C
2
3
OH
N
3
2 5
H )
O
O
O
O
O
N
2
+
H
O
obtained above (Scheme-I).
H C
3
S
O
O
The reaction was also carried out in PEG-600 as a solvent.
Thus, treatment of 1, independently, with each of dimethyl
sulphate (DMS), diethyl sulphate (DES) and benzyl chloride
(PEG-600 with chelating hydrogen)
O
OH
OH
O
S
O
O
S
H
3
C
CH3
N
N
O
+
O
O
+
Dimethyl sulphate
H
C
N
SCH
3
CH
3
(
PhCH
the use of any base, followed by simple processing, gave,
respectively, 2a (i.e., 2, R = CH ), 2b (i.e., 2, R = C ) and 2c
i.e., 2, R = PhCH ) identical with the same products obtained
above (Scheme-I). In the case of PEG-600, it was found that
the use of K CO as a base was not required. Mechanistic
2
Cl) in PEG-600 at room temperature for 2 h without
N
S
3
H
3
C
O
or
DES / Cl-CH
2
3
H
2 5
(
2
Scheme-I
2
3
similar to that of the crown ethers or that of the proton sponge
i.e., 1, 8-dimethylaminonaphthalene). The latter acts as a very
strong base due to its ability to extract hydrogen from an acidic
substrate and then retain it by chelation through lone pair of
electrons on the two nitrogen atoms of the two amino groups
Scheme-I).
(a-c) could also be prepared by an alternative method.
Thus, 1 on reaction independently, with each of dimethyl sul-
phate, diethyl sulphate and benzyl chloride under microwave
irradiation conditions for 5 min and subsequent processing,
1
0
explanation of these results is that, probably PEG-600 dis-
solves the substrates 1 and the reagent (i.e. the alkylating agent,
DMS, DES etc.), bringing them together thereby providing
an effective means for chemical reaction to occur. Further,
PEG-600 is able to extract the hydrogen from the -SH of thiou-
racil and is able to retain it in its claws by chelation through
several lone pairs of electrons in its oxygen containing chain.
The sulphanyl anion from the substrate 1 then attacks the posi-
tively polarised methyl carbon of the alkylating agent bringing
about product formation. i.e., 2 this role of PEG-600 is
(
(
2
gave, respectively 2a (i.e., 2, R = CH
3
), 2b (i.e., 2, R = C
2
H )
5
Kotaiah
