Facile regioselective green synthesis of triazolo [4,3-a] pyrimidines in aqueous medium

Article abstract of DOI:10.2174/157017809787003124

Regioselectivity is investigated in multi-component reaction of amino triazole, carbonyl compounds and α-cyano esters derivative and exclusive synthesis of triazolopyrimidines is developed in aqueous medium in excellent yields in shorter period using microwaves or ultrasonic waves. Path and mechanism of the reaction has also been discussed. The operational simplicity, environmental friendly conditions, regioselective formation of target product, high yield in significantly very short reaction time, are major benefits.

Full text of DOI:10.2174/157017809787003124

100
Letters in Organic Chemistry, 2009, 6, 100-105
Facile Regioselective Green Synthesis of Triazolo [4,3-a] Pyrimidines in
Aqueous Medium
Anshu Dandia*, Ruby Singh, Dharmendra Singh and Kapil Arya
Department of Chemistry, University of Rajasthan, Jaipur 302004, India
Received April 03, 2008: Revised September 20, 2008: Accepted September 20, 2008
Abstract: Regioselectivity is investigated in multi-component reaction of amino triazole, carbonyl compounds and ꢀ-
cyano esters derivative and exclusive synthesis of triazolopyrimidines is developed in aqueous medium in excellent
yields in shorter period using microwaves or ultrasonic waves. Path and mechanism of the reaction has also been dis-
cussed. The operational simplicity, environmental friendly conditions, regioselective formation of target product, high
yield in significantly very short reaction time, are major benefits.
Keywords: ꢀ-Cyano acrylates, microwave irradiations, ultrasound, aqueous medium, triazolopyrimidines.
INTRODUCTION
ditions or prolonged reaction times. The use of ultrasounds
in organic transformations is now well known to enhance, in
some cases, reaction rates and yield/selectivity of reactions
and in several cases facilitates organic transformation at am-
bient conditions which otherwise require drastic conditions
of temperature and pressure [24].
1,2,4-Triazole system is a structural unit of many drugs
that have antimycotic activity, e.g., Fluconazole, Itracona-
zole, Voriconzole, Tricyclazole, Furconazole, Hexaconazole,
Tetraconazole, Quinconazole, Penconazole [1-2], herbicidal
activity, e.g., Lucarbazone, Bencarbazone e.g., and Virucidal
activity, e.g., Ribavirin.
The search for alternative reaction media to replace vola-
tile, flammable and often toxic solvents commonly used in
organic synthetic procedures is an important objective of the
development of green chemical processes. From both the
environmental and economic points of view, using aqueous
media to perform organic reactions has attracted intense in-
terest, since water is the most environmentally acceptable,
safe and inexpensive solvent [25]. In addition, using water as
the solvent generally means easier workup because most
organic compounds are lipophilic and are easily separated
from aqueous media.
Further, the importance of triazolopyrimidines is well
recognized in the field of medicinal chemistry because these
heterocycles have a structure similar to that of purine and
adenine, their fused ring system differing in having the
pyrimidine nitrogen atom in a bridgehead position [3-5]. Tri-
azolo pyrimidines are useful building blocks in the synthesis
of herbicidal drugs, e.g. Metosulam, Flumetsulam, Azaf-
enidin, Diclosulam, Penoxsulam, Floransulan, and Cloran-
sulam etc.
Recently, C.M. Richardson et al. described the tria-
zolopyrimidines as novel CDK2 inhibitors [6]. Beside these
triazolopyrimidines are also useful as potential anticancer
[7], antibronchoconstrictor [8], antiviral [9], diuretic [10],
antibacterial [11] and antifungal [12] agents.
On the other hand, the utility of multi-component reac-
tions (MCRs) involving domino process with at least three
different simple substrates has emerged as a powerful strat-
egy [26]. This methodology allows molecular complexity
and diversity to be created by the facile formation of several
new covalent bonds in a one-pot transformation quite closely
approaching the concept of an ideal synthesis and is particu-
larly well adapted for combinatorial synthesis [27].
For the preparation of the complex molecules much ef-
forts have been directed towards the synthetic manipulation
of triazolopyrimidines. A number of reports dealing with the
preparation of these system have appeared, which, however,
usually require drastic conditions, long reaction times and
complex synthetic pathways and often require volatile or-
ganic solvents [13-21]. Thus new route for the synthesis of
these molecules have attracted considerable attention in
search for a rapid entry to these heterocycles.
In continuation to our general interest on the economic
and environmentally benign synthesis of biodynamic hetero-
cycles [28] and particular interest on use of aqueous medium
[29] for heterocyclic synthesis, we report herein for the first
time the microwave/ ultrasound promoted, economic,
ecofriendly, and facile multi-component regioselective syn-
thesis of triazolopyrimidines by simple addition of an equi-
molar mixture of amino triazole 1, ethyl cyanoacetate 2 and
carbonyl compound 3 in aqueous medium under micro-
waves/ultrasonic waves (Scheme 1).
In recent years, microwave-assisted reactions are well es-
tablished and have gained popularity [22]. The beneficial
effects of microwave irradiation are finding an increased role
in multiple kilogram scale in fine chemical and drugs [23],
especially in cases when usual methods require forcing con-
RESULT AND DISCUSSION
*Address correspondence to this author at the Department of Chemistry,
University of Rajasthan, Jaipur 302004, India;
E-mail: dranshudandia@yahoo.co.in
The reaction was studied under different reaction condi-
tions to find out the role of substituents, giving the products
1570-1786/09 $55.00+.00
© 2009 Bentham Science Publishers Ltd.

Facile Regioselective Green Synthesis of Triazolo
Letters in Organic Chemistry, 2009, Vol. 6, No. 1
101
N
N
NH
N
(4)
NH2
COOEt
O
CN
N
NH
MW
Aq.
H2C
+
+
N
NH2
COOEt
(1)
(2)
(3)
N
N
N
NH
(5)
H2N
EtOOC
O
O
O
3e; CH3COC6H5
3f; CH3COC6H4.4-OCH3
3a; C6H5.CHO
3b; 2-NO2.C6H4.CHO
3c;3-NO2.C6H4.CHO
3g
3h
3i
3d; 4-Cl.C6H4.CHO
Scheme 1.
Table 1. Comparative Study for Synthesis of Triazolopyrimidines [Power =600 Watt for Water and 360 Watt for Ethanol]
N
N
N
N
N
N
N
N
N
NO2
NH
NH
NH
Cl
H2N
H2N
H2N
COOEt
COOEt
COOEt
5b
5d
5h
Entry
Reaction conditions
Method
Temp.# (°C)
Time / Yield (%)
5d
5b
5h
i.
ii.
Ethanol
Ethanol + Triethylamine
Ethanol
ꢀ
Reflux
Reflux
78
Intermediate 6b
12 hrs./65
4 min./87
Intermediate 6d
10 hrs./68
5 min./91
Intermediate 6h
9 hrs./62
ꢀ
iii.
iv.
v.
MW
US
3.5 min./88
2.5 hrs./85
7 hrs./84
Ethanol
r.t
3 hrs./86
2 hrs./89
Water
ꢀ
Reflux
95
8 hrs./80
6 hrs./88
vi.
vii.
viii.
ix.
x.
Water
MW
US
6 min./94
8 min./92
10 min./96
4 hrs./90
Water
r.t
5 hrs./92
4 hrs./92
Neat (MCR)
MW
MW
US
110
96
4 min./85
3 min./88
4 min./86
Water/PTC**
4 min./85
5 min./80
7 min./90
Water/PTC**
r.t.
2.5 hrs./82
4+4* min./86
5+4 min./88
5+4 min./86
5+4 min./86
2 hrs./85
3 hrs./83
xi.
xii.
xiii.
xiv.
ꢀ-Cyano acrylates ꢁ + 1 (Ethanol)
ꢀ-Cyano acrylates + 1 (Water)
Anil ꢁꢁ+ 2 (Ethanol)
Anil + 2 (Water)
MW
MW
MW
MW
78
3+4 min./80
3+5 min./90
5+4 min./80
2.5+5 min./88
4+5 min./82
4+6 min./92
4+7 min./82
3+6 min./90
95
78
95
*4+4 indicates, first irradiation for 4 min gives intermediate (detected by TLC) and then further irradiation for 4 min after adding 3-aminotriazole.
**Cetyl trimethyl ammonium bromide is used as phase transfer catalyst.
ꢁꢀ-Cyano acrylates synthesized in situ by reaction of ethyl cyanoacetate (2) + carbonyl compound (3).
ꢁꢁAnil synthesized in situ by reaction of 2-aminotriazole (1) + carbonyl compound (3).
#The final temperature is measured at the end of microwave irradiation by introducing a glass thermometer in the reaction mixture in the beaker.

102 Letters in Organic Chemistry, 2009, Vol. 6, No. 1
Dandia et al.
in higher yields with operational simplicity. In the present
work, we studied the synthesis of 5b, 5d and 5h taking dif-
ferent parameters as shown in Table 1.
ethyl cyanoacetate 2 in ethanol and water (entry xi-xiv). The
results showed the formation of identical products as formed
in MCR reaction.
From the results obtained as shown in Table 1, it is clear
that the MCR of (1), (2) and (3) occurred successfully in
ethanol without using any catalyst under microwave and
ultrasound bath (entry iii and iv). However, intermediate 6
was formed when the reaction was carried out convention-
ally in ethanol and in absence of catalyst (entry i). The reac-
tion was also performed under neat condition in absence of
any solvent and catalyst under microwaves but the product
required further purification and recrystallization with suit-
able solvents giving comparatively lower yield (entry viii). A
very good result was obtained in aqueous medium both un-
der microwaves and ultrasonic waves giving the pure crystal-
line product upon post reaction cooling, while in case of mi-
crowaves comparatively high yield (92-94%) was achieved
in few minutes.
In order to check the general applicability for the synthe-
sis of triazolopyrimidines, benzaldehyde and other aromatic
aldehydes containing both electron withdrawing or donating
group as well as cyclic ketones were used successfully to
give the corresponding triazolopyrimidines in good to excel-
lent yields Table 2.
The multi-component condensation of amino triazole (1),
active methylene compound (2) and carbonyl compounds
(3d) shows high degree of regioselectivity to give a product
of molecular formula C14H14ClN5O2. Two possible isomeric
structures 4 and 5 were proposed, as both the amino function
and ring nitrogen in aminotriazole are active sites of nucleo-
philic attack on ꢀ,ꢁ-unsaturated nitriles. The products were
identified in all cases as structure 5 based on the chemical
and spectral data.
To further improve the procedure, reaction was also stud-
ied using cetyl trimethyl ammonium bromide as phase trans-
fer catalyst (entry ix and x) but no change in yields was ob-
served, although reaction time was reduced slightly. The
present protocol simplified the synthesis of triazolopyrimidi-
nes into a one-pot fashion under aqueous media using mi-
crowaves. Therefore, the current procedure is more facile
and friendly to environment.
The TLC monitoring of the reaction studies during the
progress of reaction indicated that intermediacy of alkene-
nitrile (6), which may result in the formation of either prod-
uct 4 or 5 involving either attack of NH2 or imino ring nitro-
gen. It is difficult to distinguish these two isomers on the
basis of spectral studies.
To confirm the pathway we have carried out the reaction
of the pre-synthesized alkene-nitrile with 2-aminotriazole
(route-A) or the reaction of anil with ethylcyanoacetate
(route B), where in all cases the identical product (5) was
The present reaction was also studied alternatively by the
step-wise synthesis which involves the reaction of ꢀ-cyano
acrylates 6 with amino-triazole 1 and reaction of anil 9 with
Table 2. Experimental, Physical and Analytical Data of Synthesized Compounds (5a-5i)
Compd
Time (min.)
Temp. (°C)
M.P. (°C)
Yield (%)
Rfa
Analysis calcd (found) %
H
C
N
5a
5b
5c
5d
5e
5f
6
6
98
95
94
95
93
96
92
94
92
129-131
124-126
115-117
168-170
142-145
240-242
228-230
340-342
254-256
92
94
94
92
86
93
92
96
93
.81
.82
.87
.75
.78
.82
.74
.78
.92
58.94
(58.73)
50.91
5.30
(5.28)
4.27
24.55
(24.47)
25.44
(50.70)
50.91
(4.29)
4.27
(25.36)
25.44
8
(50.71)
52.59
(4.25)
4.41
(25.52)
21.90
8
(52.79)
60.19
(4.43)
5.72
(21.96)
23.40
11
13
9
(60.00)
58.35
(5.74)
5.81
(23.47)
21.26
(58.55)
54.74
(5.85)
6.51
(21.20)
26.60
5g
5h
5i
(54.54)
56.30
(6.48)
6.91
(26.68)
25.25
10
12
(56.51)
62.37
(6.93)
6.47
(25.17)
21.39
(62.60)
(6.40)
(21.20
aUsing solvent system benzene : ethyl acetate (8:2).

Facile Regioselective Green Synthesis of Triazolo
Letters in Organic Chemistry, 2009, Vol. 6, No. 1
103
H
N
N
N
N
H
N
N
N
N
NH
NH
NH
N
Path i
N
NH2
COOEt
CH
C
H
COOEt
NC
CN
N
NH
COOEt
CH CH
CHO
C
COOEt
COOEt
N
NH2
7
CH
4
(1)
H2C
+
Cl
Cl
Cl
CN
Route A
Cl
(2)
N
N
N
N
H
N
Cl
N
N
(3d)
NH
N
NH
6
N
NH
H
Cl
Cl
Path ii
ꢀ-cyano acrylates
C-C
N
HN
EtOOC
NH2
COOEt
H
EtOOC
Cl
5
8
N
NH
H
N
COOEt
H
N
N
N
N
H2C
N
CHO
CN
N
NH
N
NH
N
N
CH
Cl
N
+
(2b)
N
CH
Cl
Cl
N
N
NH2
CH
N
Route B
C
C
H
H2N
(1)
COOEt
C
CH2
Cl
(3d)
HN
H
EtOOC
N
COOEt
5
11
Cl
10
9
Anil
Scheme 2. Postulated mechanism for the Synthesis of triazolo [4,3-a] pyrimidine.
obtained (Scheme 2). Thus, even in case of alkene nitrile the
product obtained results from the initial attack of the amino
group followed by cyclization at N-4 centre instead of N-2
centre as reported earlier by O. A. Kuznetsova [13].
lin Sonorex) operating at 230 V generating 33 KHz output
frequency.
GENERAL PROCEDURE
The IR spectra of 5a-5i displayed characteristic absorp-
tion in the region 3470-3240 (symmetric and asymmetric
stretching) of (NH2 & NH), 2310-2175 (CꢀN) and 1605-
1630 cm-1 (C=N). The 1HNMR spectra of 5d showed signals
at ꢁ 1.70-1.78 (t, 3H, CH3, J=6Hz), 4.20-4.35 (q, 2H, CH2,
J=6Hz), 4.62 (s, 1H, CH), 6.78 (s, 2H, NH2), 6.88-7.16 (d,
2Ar-H) 7.26-7.86 (d, 2Ar-H), 7.92 (1H, triazolic proton),
8.57 (s, 1H, NH) ppm. The presence and position of NH and
NH2 protons are confirmed by deuterium exchange. In the
mass spectrum of 5d, the molecular ion peak was observed
at m/z 319 ([M+], 70%) corresponding to its molecular
weight along with base peak at 165.
Synthesis of Ethyl 5-amino-7-(4-chlorophenyl)-7,8-
dihydro[1,2,4]triazolo[4,3-a]pyrimidine-6-carboxylate (5d).
It has been synthesized by different ways.
(A) Conventional Method
A solution of 3-amino-1,2,4-triazole (1) (0.01 mol),
ethyl cyanoacetate (2) (0.01 mol) and p-chlorobenzaldehyde
(3d) (0.01mol) in ethanol (25 ml) was refluxed for 5 days.
However, no reaction occurred after intermediate stage. Then
the reaction was continued after addition of 4-5 drops of
triethylamine, immediately a colour change occurred from
yellow to red and progress is monitored by TLC. The reac-
tion mixture was kept overnight at room temperature. The
resulting precipitate was filtered, washed with ethanol, dried
and recrystallized from ethanol.
EXPERIMENTAL
Melting points were determined on a Toshniwal appara-
tus and were uncorrected. The purity of compounds was
checked on thin layers of silica gel in various non-aqueous
solvent systems, for e.g. benzene: ethyl acetate (9:1), ben-
zene: dichloromethane (8:2). IR spectra (KBr) were recorded
(B) Microwave Activation Method
1
on a Magna FT IR–550 spectrophotometer and H NMR and
(i) Using Water
13C NMR spectra was recorded on a Bruker DRX-300 using
CDCl3 at 300.15 and 75. 47 respectively. TMS was used as
internal reference. Mass spectrum of representative com-
pound was recorded on a Kratos 50 mass spectrometer at 70
eV. The reactions were carried out in a multimode MW oven
(Panasonic-NN-781JF) equipped with inverter technology
(generating fixed frequency throughout the required time)
for realistic control of the microwave operating at 1000W
generating 2450 MHz frequency and ultrasonic bath (Bande-
A equimolar mixture of 1, 2 and 3d (.01mol) in water (8-
10 ml) in open borosil beaker covered with petridish (100
ml) was irradiated intermittently inside a microwave oven at
640 watt till the completion of reaction (TLC control). The
crystalline product started to separate out just after cooling
the reaction mixture, which was washed with water and
found to be pure by TLC, with no need of further purifica-
tion process.

104 Letters in Organic Chemistry, 2009, Vol. 6, No. 1
Dandia et al.
(ii) Neat
(C) Ultrasonic Radiation
An equimolar mixture (0.01 mol) of 1, 2 and 3d con-
tained in an open borosil beaker was placed in the micro-
wave oven and irradiated for 3 min (TLC) at 640 w. The
reaction mixture was cooled at room temperature to give
solid mass, which was crystallized from ethanol.
Equimolar quantity of 1, 2 and 3d were added in a coni-
cal flask in water (10 ml). The mixture was introduced under
ultrasonic waves using ultrasonic bath (operating at 230 V
generating 33 KHz output frequency) for 4 hrs. at room tem-
perature. The product started to separate out during the
course of reaction. The crystalline solid was filtered and
found pure on TLC with no need of further recrystallization.
(iii) Ethanol / MW:
An equimolar (.01m) quantity of 1,2 and 3d were placed
in a beaker and the minimum quantity of ethanol, sufficient
to make slurry was added. The mixture was placed in the
MW oven and irradiated at power output 360 watts intermit-
tently for 4-5 min (TLC). The product started to separate out
immediately after cooling the reaction mixture to room tem-
perature (or in some cases during the course of reaction). The
crystalline solid that separated out was filtered and found to
be pure on TLC with no need of further recrystallization.
All compounds listed in Table 2 were synthesized simi-
larly in comparatively high yields and reduced times using
water under microwave irradiation.
CONCLUSION
We have developed a simple, economic and eco-friendly
highly efficient synthetic strategy for exclusive synthesis of
triazolopyrimidines using inexpensive and commercially
Table 3. Spectral Data of Synthesized Compounds (5a- 5i)
Compd
5a
IR (cm-1)
1HNMR (ꢀ, ppm)
13CNMR (ꢀ, ppm)
3465-3235 (br, NH &
NH2), 1745 (C=O), 1625
(C=N), 1115 cm-1 (C-O)
1.70-1.88 (t, 3H, CH3, J=6.1Hz), 4.10-4.18 (q, 2H,
CH2, J=6.1Hz), 4.65 (s, 1H, CH), 6.95 (s, 2H,
NH2*), 6.82-7.72 (m, 5Ar-H), 8.10 (s, 1H, triazolic
proton) & 8.57 (s, 1H, NH*)
13.2 (CH2-CH3), 52.6 (C-7), 58.9 (CH2-CH3), 88.2 (C-
6), 122.3-143.4 (aromatic carbons), 150.3, 152.1 (two
ring C=N), 160.1 (C-5) & 168.2 (C=O)
5b
5c
5d
5e
5f
3485-3235 (br, NH &
NH2), 1730 (C=O), 1630
(C=N), 1570 & 1385
(NO2), 1095 cm-1 (C-O)
1.73-1.78 (t, 3H, CH3, J=6.3Hz), 4.20-4.25 (q, 2H,
CH2, J=6.3Hz), 4.73 (s, 1H, CH), 6.90 (s, 2H,
NH2*), 6.89-7.62 (m, 4Ar-H), 8.50 (s, 1H triazolic
proton) & 8.97 (s, 1H, NH*)
13.5 (CH2-CH3), 42.8 (C-7), 56.6 (CH2-CH3), 87.3 (C-
6), 121.5-141.2 (aromatic carbons), 151.3, 152.9 (two
ring C=N) 161.3 (C-5) & 166.2 (C=O)
3475-3245 (br, NH &
NH2), 1740 (C=O), 1635
(C=N), 1575 & 1380
(NO2), 1075 cm-1 (C-O)
1.80-1.88 (t, 3H, CH3, J=6.2Hz), 4.30-4.35 (q, 2H,
CH2, J=6.2Hz), 4.52 (s, 1H, CH), 6.70 (s, 2H, NH2*, 6), 120.5-141.3 (aromatic carbons), 152.3, 153.6 (two
6.88-7.66 (m, 4Ar-H), 8.20 (s, 1H triazolic proton)
& 8.77 (s, 1H, NH*)
12.7 (CH2-CH3), 48.6 (C-7), 57.3 (CH2-CH3), 88.3 (C-
ring C=N), 161.4 (C-5) & 166.4 (C=O)
3470-3240 (br, NH &
NH2), 2920-2880 (br, ali.
CH), 1735 (C=O), 1630
(C=N), 1130 cm-1 (C-O)
1.70-1.78 (t, 3H, CH3, J=6Hz), 4.20-4.35 (q, 2H,
CH2, J=6Hz), 4.62 (s, 1H, CH), 6.78 (s, 2H, NH2*),
6.88-7.16 (d, 2Ar-H) 7.26-7.86 (d, 2Ar-H), 7.92 (s,
1H, triazolic proton), 8.57 (s, 1H, NH*)
13.9 (CH2-CH3), 55.4 (C-7), 60.2 (CH2-CH3), 86.2 (C-
6), 122.3-139.3 (aromatic carbons), 152.6, 153.2 (two
ring C=N), 152.4 (C-5) & 167.2 (C=O)
3440-3220 (br, NH &
NH2), 2925-2875 (br, ali.
CH), 1715 (C=O), 1620
(C=N), 1150 cm-1 (C-O)
1.72-1.75 (t, 3H, CH3, J=6.4Hz), 2.02 (s, 3H, CH3),
4.22-4.31 (q, 2H, CH2, J=6.4Hz), 6.70 (s, 2H,
NH2*), 7.88-8.21(m, 5Ar-H & 1H triazolic proton),
8.78 (s, 1H, NH*)
12.8 (CH2-CH3), 28.6 (CH3), 52.3 (C-7), 58.4 (CH2-
CH3), 85.4 (C-6), 125.2-140.3 (aromatic carbons),
150.2, 153.1 (two ring C=N), 160.2 (C-5) & 167.1
(C=O)
3435-3215 (br, NH &
NH2), 2935-2885 (br, ali.
CH), 1720 (C=O), 1615
(C=N), 1130 cm-1 (C-O)
1.71-1.74 (t, 3H, CH3, J=6.3Hz), 2.05 (s, 3H, CH3),
3.59 (s, 3H, OCH3), 4.25-4.33 (q, 2H, CH2,
J=6.3Hz), 6.70 (s, 2H, NH2*), 6.78-6.88 (d, 2Ar-H),
6.96-6.88 (d, 2Ar-H), 8.01(1H triazolic proton),
8.78 (s, 1H, NH*)
14.6 (CH2-CH3), 26.4 (CH3), 54.1 (C-7), 54.6 (OCH3),
55.2 (CH2-CH3), 87.4 (C-6), 126.8-153.6 (aromatic
carbons), 153.1, 154.1 (two ring C=N), 161.1 (C-5) &
169.3 (C=O)
5g
5h
3485-3245 (br, NH &
NH2), 2925-2865 (br, ali.
CH), 1740 (C=O), 1625
(C=N), 1090 cm-1 (C-O)
1.42-1.45 (t, 3H, CH3, J=6Hz), 1.45-1.72 (t, 4H,
CH2), 1.85-1.98 (m, 4H, CH2), 4.25-4.45 (q, 2H,
CH2, J=6Hz), 5.97 (s, 2H, NH2*), 7.95 (s, 1H, tria-
zolic proton), 9.80 (s, 1H, NH*)
12.4 (CH2-CH3), 17.5 (2CH2, cyclo pantane ring), 37.3
(2CH2, cyclo pantane ring), 53.3 (spiro carbon), 57.3
(CH2-CH3), 97.6 (C-6), 152.3, 154.1 (two ring C=N),
162.2 (C-5) & 168.4 (C=O)
3465-3240 (br, NH &
NH2), 2935-2875 (br, ali.
CH), 1760 (C=O),
1645(C=N), 1070 cm-1 (C-
O)
1.22-1.46 (t, 3H, CH3, J=6Hz), 1.60-1.75 (t, 4H,
CH2), 1.92-2.09 (m, 2H, CH2), 2.21-2.54 (t, 4H,
CH2), 3.99-4.35 (q, 2H, CH2, J=6Hz), 6.55 (s, 2H,
NH2*), 7.92 (s, 1H, triazolic proton), 9.70 (s, 1H,
NH*)
13.9 (CH2-CH3), 21.2 (2CH2, cyclo hexane ring), 29.3
(CH2, cyclohexane ring), 35.1 (2CH2, cyclohexane
ring), 48.1 (spiro carbon), 61.1 (CH2-CH3), 93.4 (C-6),
), 151.3, 153.1 (two ring C=N), 161.7 (C-5) & 167.2
(C=O)
5i
3475-3245 (br, NH &
NH2), 2925-2870 (br, ali.
CH), 1740 (C=O), 1605
(C=N), 1140 cm-1 (C-O)
1.50-1.62 (m, 2H, CH2), 1.65-1.78 (t, 3H, CH3,
J=6Hz), 1.98-2.04 (t, 2H, CH2), 2.15-2.48 (t, 2H,
CH2), 4.20-4.32 (q, 2H, CH2, J=6Hz), 5.87 (s, 2H,
NH2*), 7.05 (t, 1H,), 7.15 (t, 1H), 7.35 (d, 1H,
J=2Hz), 7.66 (d, 1H, J=8Hz), 7.95 (s, 1H triazolic
proton) & 8.79 (s, 1H, NH*)
-
*Presence and position of NH and NH2 protons are confirmed by deuterium exchange.

Facile Regioselective Green Synthesis of Triazolo
Letters in Organic Chemistry, 2009, Vol. 6, No. 1
105
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ACKNOWLEDGEMENTS
Financial assistance from Council for Scientific and In-
dustrial Research (01/ 2248/08/EMR-II, 9/149/398/2005/
EMR-I), New Delhi are gratefully acknowledged. We are
also thankful to Regional Sophisticated Instrumentation Cen-
tre Chandigarh, and Central Drug Research Institute,
Lucknow, for the elemental and spectral analyses.
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