Three-component synthesis of some 2-amino-5-hydroxy-[1,2,4]triazolo[1,5-a] pyrimidine-6-carbonitriles and 2-(cyanoamino)-4-hydroxypyrimidine-5- carbonitriles

Article abstract of DOI:10.1007/s00706-010-0371-8

Nine new 2-amino-5-hydroxy-[1,2,4]triazolo-[1,5-a]pyrimidine-6- carbonitriles and eight 2-(cyanoamino)-4-hydroxypyrimidine-5-carbonitriles have been synthesized in a simple and convenient method by three-component condensation of aromatic aldehydes, ethyl

Full text of DOI:10.1007/s00706-010-0371-8

Monatsh Chem (2010) 141:1101–1106
DOI 10.1007/s00706-010-0371-8
ORIGINAL PAPER
Three-component synthesis of some 2-amino-5-hydroxy-
[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitriles and
2-(cyanoamino)-4-hydroxypyrimidine-5-carbonitriles
•
Reza Ranjbar-Karimi Khalil Beiki-Shoraki
•
Asghar Amiri
Received: 29 March 2010 / Accepted: 3 August 2010 / Published online: 8 September 2010
Ó Springer-Verlag 2010
Abstract Nine new 2-amino-5-hydroxy-[1,2,4]triazolo-
[1,5-a]pyrimidine-6-carbonitriles and eight 2-(cyanoamino)-
4-hydroxypyrimidine-5-carbonitriles have been synthesized
in a simple and convenient method by three-component
condensation of aromatic aldehydes, ethyl cyanoacetate, and
3,5-diamino-1,2,4-triazole or cyanoguanidine hydrochloride
in alkaline ethanol. All new synthesized compounds were
characterized bynuclear magneticresonance (NMR), infrared
(IR), ultraviolet (UV), mass spectrometry (MS), and ele-
mental analyses.
analgesic, anti-inflammatory, antiparkinsonian, and andro-
genic–anabolic activities [10–12].
It is well known that multicomponent reactions (MCR)
consisting of two or more synthetic steps, which are carried
out without isolation of any intermediate, allow to reduce
time and save money, energy, and raw materials. Also, the
development of simple synthetic routes for widely used
organic compounds from readily available reagents is one
of the major tasks in organic synthesis.
Manyliterature reportsconcerningthe synthesis ofsystems
incorporating a triazolopyrimidine moiety [13] either start
from reaction of hydrazine with an acid derivative (orthofor-
mate [14] or activated acids [15]) or via oxidative cyclization
of a hydrazone with reagents such as N-Bromosuccinimide
(NBS) [16], lithium iodide or sodium carbonate [17],
Pb(OAc)4 [18], FeCl3 [19], and iodobenzene diacetate [20].
In this paper, we report the first synthesis of some amino
derivatives of triazolopyrimidine by three-component
condensation of aromatic aldehydes, ethyl cyanoacetate,
and 3,5-diamino-1,2,4-triazole in alkaline ethanol.
Keywords Triazolopyrimidine ꢀ Pyrimidine ꢀ Aldehyde ꢀ
Three-component synthesis ꢀ Triazole
Introduction
Fused triazole and pyrimidine ring systems have been an
interesting topic in the fields of medicinal and agricultural
chemistry for many years [1, 2]. Among their important
effects, some triazolopyrimidine derivatives are known as
dual thrombin/factor Xa inhibitors [3], blood pressure reg-
ulators [4], antibacterial agents [5], human adenosine A2a
and A3 receptor ligands [6], and cardiovascular vasodilators
[7]. Additionally, many triazolopyrimidine-2-sulfonamide
derivatives, such as florasulam, flumetsulam, and metosu-
lam, are commercially available as acetolactate synthase-
inhibiting herbicides [8, 9]. Recently some new substituted
pyrimidine derivatives have been synthesized, which exhibit
Results and discussion
One of the most widely used routes for preparation of
2-amino-1,2,4-triazolo[1,5-a]pyrimidines is cyclocondensa-
tion of 3,5-diamino-1,2,4-triazole with unsaturated aldehydes
and ketones followed by heteroaromatization of the resulting
2-amino-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidines [21,
22]. There is no report concerning one-pot synthesis of
2-amino-[1,2,4]triazolopyrimidine compounds using aro-
matic aldehydes, ethyl cyanoacetate, and 3,5-diamino-1,2,4-
triazole. Of course synthesis of 2-amino-6-hydroxy-4-
arylpyrimidine-5-carbonitriles has been developed by
three-component condensation of aromatic aldehydes, ethyl
R. Ranjbar-Karimi (&) ꢀ K. Beiki-Shoraki ꢀ A. Amiri
Department of Chemistry, Faculty of Science, Vali-e-Asr
University, 77176 Rafsanjan, Islamic Republic of Iran
e-mail: karimi_r110@yahoo.com
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R. Ranjbar-Karimi et al.
Table 1 Synthesis of 2-amino-
[1,2,4]triazolopyrimidine
derivatives
NH2
N
N
H2N
N
H
Ar
Ar
CN
CN
N
4
N
Ar-CHO
NC CO2Et
H2N
+
OH
N
N
H
CO2Et
EtOH, NaOH
1
2
5a-5i
3
Product
Aldehyde
Time (min)
Yield (%)
5a
5b
5c
5d
5e
5f
180
145
140
150
140
160
160
85
83
89
91
92
93
90
CHO
HO
CHO
MeO
Me2N
Me
CHO
CHO
CHO
O2N
CHO
MeO
5g
CHO
MeO
5h
5i
140
160
90
92
N
S
CHO
CHO
cyanoacetate, and guanidine hydrochloride [23]. The target
products 5a–5i were synthesized by a three-component con-
densation procedure as shown in Table 1. Firstly, the
aromatic aldehyde 1 reacted with ethyl cyanoacetate (2) to
affordintermediate 3, which cyclizedwith3,5-diamino-1,2,4-
triazole (4) to give 2-amino-[1,2,4]triazolopyrimidines 5a–5i.
The formation of the products 5a–5i is assumed to take place
via an initial addition of the more nucleophilic endocyclic
nitrogen in 3,5-diamino-1,2,4-triazole to the intermediate 3
with subsequent intramolecular cyclization and aromatization
to give the final products 5a–5i, adapting a mechanism pos-
tulated by Shaaban [24]. The method exploited works well
with a variety of aromaticaldehydes as well as heteroaromatic
aldehydes to afford corresponding 2-amino-[1,2,4]triazolo-
pyrimidine derivatives in excellent yields (Table 1). We
reasoned that electron-donating as well as electron-with-
drawing groups present in aryl aldehydes do not alter the
theme of the method in terms of yield. The mass spectrum of
compound 5a, taken as an example of the prepared series,
1 reacted with ethyl cyanoacetate (2) to afford intermediate 3,
which cyclized with cyanoguanidine hydrochloride (6) to
give 2-(cyanoamino)-4-hydroxypyrimidine-5-carbonitriles
7a–7h.
We used a series of aromatic and heteroaromatic
aldehydes having electron-donating as well as electron-
withdrawing substituents to obtain the corresponding
2-(cyanoamino)-4-hydroxypyrimidine-5-carbonitriles (Table 2).
As can be seen from Table 2, when aromatic aldehydes
containing electron-donating groups were employed, a
longer reaction time was required than those of electron-
withdrawing groups on aromatic rings. The structures of all
compounds were characterized by 1H NMR, 13C NMR, IR,
MS, and elemental analyses.
Conclusion
Herein we report synthesis of several new 2-amino-
5-hydroxy[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitriles
5a–5i and 2-(cyanoamino)-4-hydroxypyrimidine-5-carbo-
nitriles 7a–7h via a simple and convenient method by
three-component condensation of aromatic aldehydes,
ethyl cyanoacetate, and 3,5-diamino-1,2,4-triazole or
cyanoguanidine hydrochloride, respectively, in alkaline
ethanol. The method exploited works well with a variety of
aromatic aldehydes as well as heteroaromatic aldehydes to
afford corresponding triazolopyrimidine and pyrimidine
1
revealed a molecular ion peak at m/z = 252. Its H NMR
spectrum revealed a broad singlet signal at d = 3.4 ppm due
to NH2 protons and multiple signals at d = 6.9–7.9 ppm due
to phenyl protons, in addition to a singlet signal at 13.1 ppm
due to the OH proton. With this encouraging result in hand,
we attempted the synthesis of some 2-(cyanoamino)-
4-hydroxypyrimidine-5-carbonitrile compounds. Products
7a–7h were synthesized by a three-component condensation
procedure as shown in Table 2. Firstly, the aromatic aldehyde
123

Three-component synthesis of some 2-amino-5-hydroxy-[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitriles
1103
Table 2 Synthesis of
H
2-(cyanoamino)-4-
hydroxypyrimidine-5-
carbonitriles
N
NH2
NC
Ar
NH .HCl
CN
OH
6
Ar
CN
N
NC CO2Et
+
Ar-CHO
NC
N
N
H
CO2Et
EtOH, NaOH
H
7a-7h
1
2
3
Product
Aldehyde
Time (min)
Yield (%)
7a
7b
7c
7d
7e
7f
150
160
158
160
155
140
150
89
85
81
78
75
83
85
CHO
HO
CHO
CHO
CHO
CHO
CHO
MeO
Me2N
Me
O2N
MeO
7g
CHO
MeO
N
7h
148
86
CHO
cyanamide derivatives in excellent yields (Tables 1, 2).
Electron-donating as well as electron-withdrawing groups
present in aryl aldehydes do not alter the theme of the
method in terms of yield.
completion of reaction as monitored by TLC. After
reaction completion (140–180 min), the reaction mixture
was poured into iced water and neutralized by HCl (1:1)
to get the desired product. The separated solid was filtered
and washed with little distilled water to remove acid.
Finally, the crude product was purified by recrystallization
from ethanol to get pure product in almost quantitative
yield.
Experimental
All reagents and solvents were purchased from Merck and
Aldrich and used without further purification. The reactions
were carried out under an atmosphere of air unless other-
wise specified. The elemental analyses for C, H, and N
were performed using a Heraeus CHN-O-Rapid analyzer,
and results agreed with calculated values. 1H NMR spectra
were recorded at 500 MHz and 13C NMR spectra at
125 MHz on a Bruker spectrometer. Chemical shifts are
reported in ppm relative to tetramethylsilane as internal
standard. Mass spectra were taken by a Micromass Plat-
form II in electrospray ionization (EI) mode (70 eV). Silica
plates (Merck) were used for thin-layer chromatography
(TLC) analysis.
2-Amino-5-hydroxy-7-phenyl[1,2,4]triazolo[1,5-a]-
pyrimidine-6-carbonitrile (5a, C12H8N6O)
White solid; m.p.: 182–184 °C (EtOH); IR (KBr):
ꢀ
m = 3,360, 3,310, 2,831, 2,229, 1,721, 1,583, 1,559, 1,460,
1,428, 1,262, 806 cm-1; UV–vis (95% EtOH): kmax = 420,
1
410, 265 nm; H NMR (CDCl3): d = 3.9 (bs, 2H, NH2),
6.91–7.92 (m, 5H, Ar–H), 13.11 (bs, 1H, OH) ppm; 13C
NMR (CDCl3): d = 94.31, 112.61, 117.81, 118.53, 134.40,
148.13, 151.34, 153.47, 153.72, 164.75 ppm; MS (EI):
m/z = 252 (M?), 225, 175, 147.
2-Amino-5-hydroxy-7-(4-hydroxyphenyl)[1,2,4]triazolo-
[1,5-a]pyrimidine-6-carbonitrile (5b, C12H8N6O2)
Yellow solid; m.p.: 192–194 °C (EtOH); IR (KBr):
ꢀ
General procedure for the synthesis
of triazolopyrimidine derivatives
m = 3,341, 3,315, 2,842, 2,230, 1,625, 1,589, 1,568, 1,462,
1,425, 1,232, 805 cm-1; UV–vis (95% EtOH): kmax = 415,
1
413, 260 nm; H NMR (CDCl3): d = 3.30 (bs, 2H, NH2),
Aromatic aldehyde (10 mmol) and ethyl cyanoacetate
(10 mmol) were added to 6 cm3 2 M NaOH solution in
25 cm3 ethanol. The mixture was stirred mechanically for
15 min, then 3,5-diamino-1,2,4-triazole (10 mmol) was
added and the reaction mixture was refluxed until
3.51 (bs, 1H, OH), 7.16 (d, J = 9.1 Hz, 2H, Ar–H), 7.15 (d,
J = 9.1 Hz, 2H, Ar–H), 8.75 (bs, 1H, OH) ppm; 13C NMR
(CDCl3): d = 96.22, 113.63, 116.56, 122.93, 133.63,
147.00, 150.31, 152.49, 166.03, 166.71 ppm; MS (EI):
m/z = 268 (M?), 242, 191, 165.
123

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R. Ranjbar-Karimi et al.
2-Amino-5-hydroxy-7-(4-methoxyphenyl)[1,2,4]-
triazolo[1,5-a]pyrimidine-6-carbonitrile
(5c, C13H10N6O2)
2-Amino-7-(3,5-dimethoxyphenyl)-5-hydroxy[1,2,4]-
triazolo[1,5-a]pyrimidine-6-carbonitrile
(5g, C14H12N6O3)
White solid; m.p.: 102–104 °C (EtOH); IR (KBr):
Brown solid; m.p.: 172–175 °C (EtOH); IR (KBr):
ꢀ
ꢀ
m = 3,345, 3,321, 2,835, 2,227, 1,740, 1,585, 1,567, 1,471,
m = 3,349, 3,310, 2,838, 2,222, 1,708, 1,580, 1,566,
1,452, 1,244, 802 cm-1; UV–vis (95% EtOH): kmax = 421,
1,452, 1,448, 1,220, 825 cm-1; UV–vis (95% EtOH):
1
1
417, 250 nm; H NMR (CDCl3): d = 3.83 (bs, 2H, NH2),
kmax = 421, 410, 241 nm; H NMR (CDCl3): d = 3.80 (s,
3H, CH3), 3.81 (s, 3H, CH3), 3.28 (bs, 2H, NH2), 6.09 (s,
3.85 (s, 3H, CH3), 7.14 (d, J = 8.9 Hz, 2H, Ar–H), 8.06 (d,
J = 8.9 Hz, 2H, Ar–H), 8.30 (s, 1H, OH) ppm; 13C NMR
(CDCl3): d = 53.73, 98.24, 114.94, 116.18, 123.90, 133.50,
145.13, 154.53, 155.41, 162.85, 163.56 ppm; MS (EI):
m/z = 282 (M?), 252, 227, 211, 135.
1H, Ar–H), 8.02 (s, 2H, Ar–H), 9.22 (s, 1H, OH) ppm; 13
C
NMR (CDCl3): d = 54.12, 55.09, 98.58, 114.23, 117.35,
123.04, 133.92, 135.43, 148.27, 151.13, 153.60,
167.12 ppm; MS (EI): m/z = 312 (M?), 287, 282, 252,
176.
2-Amino-7-(4-(dimethylamino)phenyl)-5-hydroxy-
[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile
(5d, C14H13N7O)
2-Amino-5-hydroxy-7-(4-pyridyl)[1,2,4]-
triazolo[1,5-a]pyrimidine-6-carbonitrile
(5h, C11H7N7O)
Yellow solid; m.p.: 225–226 °C (EtOH); IR (KBr):
ꢀ
m = 3,361, 3,318, 2,830, 2,230, 1,716, 1,582, 1,562, 1,459,
Yellow solid; m.p.: 229–231 °C (EtOH); IR (KBr):
1,450, 1,231, 800 cm-1; UV–vis (95% EtOH): kmax = 426,
411, 256 nm; 1H NMR (CDCl3): d = 3.06 (s, 6H, CH3), 3.31
(bs, 2H, NH2), 6.81 (d, J = 9.1 Hz, 2H, Ar–H), 7.92 (d,
J = 9.1 Hz, 2H, Ar–H), 13.27 (s, 1H, OH) ppm; 13C NMR
(CDCl3): d = 42.12, 96.21, 111.64, 117.88, 118.39, 133.43,
133.50, 142.16, 148.73, 153.47, 153.72, 164.75 ppm; MS
(EI): m/z = 295 (M?), 279, 270, 252, 176, 151, 135.
m = 3,347, 3,316, 2,840, 2,214, 1,702, 1,586, 1,583, 1,450,
ꢀ
1,443, 1,271, 815 cm-1; UV–vis (95% EtOH): kmax = 426,
1
407, 246 nm; H NMR (CDCl3): d = 3.41 (bs, 2H, NH2),
7.41 (d, J = 8.2 Hz, 2H, Py-H), 8.23 (d, J = 8.2 Hz, 2H,
Py-H), 9.81 (s, 1H, OH) ppm; 13C NMR (CDCl3):
d = 97.23, 113.27, 118.31, 122.63, 132.25, 147.20,
152.62, 155.61, 168.44 ppm; MS (EI): m/z = 253 (M?),
228, 229, 176.
2-Amino-5-hydroxy-7-(4-methylphenyl)[1,2,4]triazolo-
[1,5-a]pyrimidine-6-carbonitrile (5e, C13H10N6O)
White solid; m.p.: 234–235 °C (EtOH); IR (KBr):
2-Amino-5-hydroxy-7-(2-thienyl)[1,2,4]triazolo-
[1,5-a]pyrimidine-6-carbonitrile (5i, C10H6N6OS)
ꢀ
m = 3,352, 3,323, 2,228, 1,700, 1,574, 1,559, 1,449,
ꢀ
Red solid; m.p.: 229–231 °C (EtOH); IR (KBr): m = 3,340,
1,445, 1,237, 814 cm-1
;
UV–vis (95% EtOH):
3,320, 2,218, 1,717, 1,580, 1,575, 1,430, 1,449, 1,201,
805 cm-1; UV–vis (95% EtOH): kmax = 416, 410, 241 nm;
1H NMR (CDCl3): d = 3.55 (bs, 2H, NH2), 7.34 (dd,
J = 8.2, 7.3 Hz, 1H, Th–H), 8.05 (d, J = 8.2 Hz, 1H,
Th–H), 8.20 (d, J = 7.3 Hz, 1H, Th–H), 9.81 (s, 1H, OH)
ppm; 13C NMR (CDCl3): d = 97.50, 116.79, 128.68,
128.83, 135.49, 137.17, 139.36, 140.25, 147.77,
162.61 ppm; MS (EI): m/z = 258 (M?), 228, 229, 176.
kmax = 413, 410, 242 nm; 1H NMR (CDCl3): d = 2.21
(s, 3H, CH3), 3.51 (bs, 2H, NH2), 7.01 (d, J = 8.2 Hz, 2H,
Ar–H), 7.98 (d, J = 8.2 Hz, 2H, Ar–H), 12.21 (s, 1H, OH)
ppm; 13C NMR (CDCl3): d = 43.12, 93.40, 112.16,
117.81, 119.23, 132.85, 133.17, 140.20, 148.13, 151.79,
152.74, 165.83 ppm; MS (EI): m/z = 266 (M?), 252, 250,
241, 176, 151, 135.
2-Amino-5-hydroxy-7-(4-nitrophenyl)[1,2,4]-
triazolo[1,5-a]pyrimidine-6-carbonitrile
(5f, C12H7N7O3)
General procedure for the synthesis of (cyanoamino)
pyrimidine derivatives
Brown solid; m.p.: 160–163 °C (EtOH); IR (KBr):
m = 3,355, 3,319, 2,815, 2,233, 1,710, 1,579, 1,562,
ꢀ
Aromatic aldehyde (10 mmol) and ethyl cyanoacetate
(10 mmol) were added to 6 cm3 2 M NaOH solution in
25 cm3 ethanol. The mixture was stirred mechanically for
15 min, then cyanoguanidine hydrochloride (10 mmol)
was added and the reaction mixture was refluxed until
completion of reaction as monitored by TLC. After reac-
tion completion (140–160 min), the reaction mixture was
poured into iced water and neutralized by HCl (1:1) to get
1,450, 1,447, 1,231, 804 cm-1; UV–vis (95% EtOH):
kmax = 417, 415, 248 nm; 1H NMR (CDCl3): d = 3.12
(bs, 2H, NH2), 7.21 (d, J = 8.6 Hz, 2H, Ar–H), 8.09 (d,
J = 8.6 Hz, 2H, Ar–H), 11.01 (s, 1H, OH) ppm; 13C NMR
(CDCl3): d = 95.42, 112.19, 116.57, 119.24, 133.81,
134.46, 140.55, 147.18, 150.93, 152.63, 166.43 ppm; MS
(EI): m/z = 297 (M?), 281, 272, 252, 176, 151, 135.
123

Three-component synthesis of some 2-amino-5-hydroxy-[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitriles
1105
UV–vis (95% EtOH): kmax = 354, 262 nm; 1H NMR
(CDCl3): d = 2.57 (s, 3H, CH3), 3.61 (bs, 1H, NH), 6.80
(d, J = 8.1 Hz, 2H, Ar–H), 7.21 (d, J = 8.1 Hz, 2H, Ar–H),
8.26 (s, 1H, OH) ppm; 13C NMR (CDCl3): d = 28.67, 90.55,
112.10, 116.48, 117.49, 132.80, 151.73, 154.44,
165.67 ppm; MS (EI): m/z = 251 (M?), 237, 161.
the desired product. The separated solid was filtered and
washed with little distilled water to remove acid. Finally,
the crude product was purified by recrystallization from
ethanol to get pure product in almost quantitative yield.
2-(Cyanoamino)-4-hydroxy-6-phenylpyrimidine-5-
carbonitrile (7a, C12H7N5O)
2-(Cyanoamino)-4-hydroxy-6-(4-nitrophenyl)pyrimidine-5-
carbonitrile (7f, C12H6N6O3)
White solid; m.p.: 120–122 °C (EtOH); IR (KBr):
m = 3,342, 3,319, 2,232, 1,705, 1,575, 1,566, 1,420,
ꢀ
1,410, 822 cm-1; UV–vis (95% EtOH): kmax = 375,
252 nm; 1H NMR (CDCl3): d = 4.13 (bs, 1H, NH),
7.01–8.02 (m, 5H, Ar–H), 8.43 (s, 1H, OH) ppm; 13C
NMR (CDCl3): d = 94.11, 112.24, 116.60, 118.35, 134.81,
136.35, 152.74, 153.04, 147.77, 164.56 ppm; MS (EI):
m/z = 237 (M?), 212, 197, 161, 96.
Orange solid; m.p.: 130–132 °C (EtOH); IR (KBr):
ꢀ
m = 3,382, 3,210, 2,843, 2,223, 1,681, 1,556, 1,429,
838 cm-1; UV–vis (95% EtOH): kmax = 371, 261 nm;
1H NMR (CDCl3): d = 6.13 (bs, 1H, NH), 7.23–8.21 (m,
4H, Ar–H), 8.71 (s, 1H, OH) ppm; 13C NMR (CDCl3):
d = 99.87, 113.15, 116.44, 118.24, 133.46, 134. 25,
152.13, 153.56, 166.51 ppm; MS (EI): m/z = 282 (M?),
237, 161.
2-(Cyanoamino)-4-hydroxy-6-(4-hydroxyphenyl)-
pyrimidine-5-carbonitrile (7b, C12H7N5O2)
2-(Cyanoamino)-6-(3,5-dimethoxyphenyl)-4-hydroxy-
pyrimidine-5-carbonitrile (7g, C14H11N5O3)
White solid; m.p.: 166–168 °C (EtOH); IR (KBr):
ꢀ
m = 3,432, 3,220, 2,905, 2,247, 1,715, 1,676, 1,575,
Yellow solid; m.p.: 118–120 °C (EtOH); IR (KBr):
1,566, 1,432, 1,420, 834 cm-1; UV–vis (95% EtOH):
ꢀ
m ¼ 3;341; = 3,341, 3,320, 2,841, 2,227, 1,640, 1,565,
1
kmax = 382, 262 nm; H NMR (CDCl3): d = 3.70 (s, 1H,
NH), 4.52 (s, 1H, OH), 6.89 (d, J = 8.1 Hz, 2H, Ar–H),
7.85 (d, J = 8.1 Hz, 2H, Ar–H), 8.16 (s, 1H, OH) ppm; 13
1,451, 1,440, 815 cm-1
;
UV–vis (95% EtOH):
1
kmax = 356, 251 nm; H NMR (CDCl3): d = 3.76 (s, 3H,
CH3), 3.79 (s, 3H, CH3), 3.91 (bs, 1H, NH), 6.23 (s, 1H,
Ar–H), 8.35 (s, 2H, Ar–H), 8.20 (s, 1H, OH) ppm; 13C
NMR (CDCl3): d = 53.10, 54.22, 95.51, 113.21, 116.61,
128.55, 132.91, 134.81, 147.20, 152.19, 155.65,
166.19 ppm; MS (EI): m/z = 397 (M?), 267, 237.
C
NMR (CDCl3): d = 93.10, 113.21, 117.69, 118.36, 133.82,
137.30, 147.67, 151.46, 153.55, 165.16 ppm; MS (EI):
m/z = 253 (M?), 228, 161.
2-(Cyanoamino)-4-hydroxy-6-(4-methoxyphenyl)-
pyrimidine-5-carbonitrile (7c, C13H9N5O2)
2-(Cyanoamino)-4-hydroxy-6-(4-pyridyl)-
pyrimidine-5-carbonitrile (7h, C11H6N6O)
White solid; m.p.: 122–124 °C (EtOH); IR (KBr):
ꢀ
m = 3,339, 3,210, 2,825, 2,243, 1,668, 1,583, 1,562,
Yellow solid; m.p.: 190–192 °C (EtOH); IR (KBr):
1,421, 804 cm-1; UV–vis (95% EtOH): kmax = 371,
ꢀ
m = 3,351, 3,326, 2,821, 2,219, 1,652, 1,580, 1,456,
1
1,441, 805 cm-1; UV–vis (95% EtOH): kmax = 352,
261 nm; H NMR (CDCl3): d = 2.82 (bs, 1H, NH), 3.87
1
(s, 3H, CH3), 7.14–8.01 (m, 4H, Ar–H), 8.10 (s, 1H, OH)
ppm; 13C NMR (CDCl3): d = 53.26, 96.18, 113.14,
116.57, 117.64, 130.76, 135.30, 150.04, 153.67, 146.71,
163.55 ppm; MS (EI): m/z = 267 (M?), 237, 161.
257 nm; H NMR (CDCl3): d = 3.81 (bs, 1H, NH), 7.40
(d, J = 8.0 Hz, 2H, Py-H), 8.15 (d, J = 8.0 Hz, 2H, Py-
H), 9.63 (s, 1H, OH) ppm; 13C NMR (CDCl3): d = 93.66,
113.56, 117.41, 123.51, 133.20, 135.41, 153.66, 155.60,
166.53 ppm; MS (EI): m/z = 238 (M?), 161.
2-(Cyanoamino)-4-(4-(dimethylamino)phenyl)-6-
hydroxypyrimidine-5-carbonitrile (7d, C14H12N6O)
Acknowledgments Support of this investigation by Vali-E-Asr
University is gratefully acknowledged.
ꢀ
Red solid; m.p.: 140–142 °C (EtOH); IR (KBr): m = 3,341,
3,247, 2,827, 2,251, 1,670, 1,572, 1,558, 1,449, 813 cm-1
;
UV–vis (95% EtOH): kmax = 368, 268 nm; 1H NMR
(CDCl3): d = 3.07 (s, 6H, CH3), 3.78 (bs, 1H, NH), 6.82
(d, J = 7.9 Hz, 2H, Ar–H), 7.95 (d, J = 7.9 Hz, 2H, Ar–
H), 8.10 (s, 1H, OH) ppm; 13C NMR (CDCl3): d = 52.62,
91.69, 111.70, 117.51, 118.27, 133.81, 153.77, 154.26,
163.98 ppm; MS (EI): m/z = 280 (M?), 237, 161.
References
1. Vu CB, Shields P, Peng B, Kumaravel G, Jin XW, Phadke D,
Wang J, Engber T, Ayyub E, Petter RC (2004) Bioorg Med Chem
Lett 14:4835
2. Jackson R, Ghosh D, Paterson G (2000) Pest Manage Sci 56:1065
3. Deng JZ, McMasters DR, Rabbat PMA, Williams PD, Coburn
CA, Yan Y, Kuo LC, Lewis SD, Lucas BJ, Krueger JA, Strulovici
B, Vacca JP, Lylea TA, Burgey CS (2005) Bioorg Med Chem
Lett 15:4411
2-(Cyanoamino)-4-hydroxy-6-(4-methylphenyl)pyrimidine-
5-carbonitrile (7e, C13H9N5O)
ꢀ
White solid; m.p.: 89–102 °C (EtOH); IR (KBr): m = 3,336,
4. Rusinov VL, Petrov AY, Pilicheva TL (1986) Khim Farm Zh
20:178
3,232, 2,810, 2,262, 1,690, 1,562, 1,551, 1,440, 823 cm-1
;
123

1106
R. Ranjbar-Karimi et al.
5. Rusinov VL, Myasnikov AV, Pilicheva TL (1990) Khim Farm Zh
24:39
15. Wang Y, Sarris K, Sauer DR, Djuric SW (2007) Tetrahedron Lett
48:2237
6. Okamura T, Kurogi Y, Hashimoto K, Nishikawa K, Nagao Y
(2004) Bioorg Med Chem Lett 14:2443
7. Novinson T, Springer RH, O’Brien DE, Scholten MB, Miller JP,
Robins RK (1982) J Med Chem 25:420
8. Kleschick WA, Costales MJ, Dunbar JE, Meikle RW, Monte WT,
Pearson NR, Snider SW, Vinogradoff AP (1990) Pestic Sci
29:341
9. Chen Q, Zhu X-L, Jiang L-L, Liu Z-M, Yang G-F (2008) Eur J
Med Chem 43:595
10. Amr AE, Hegab MI, Ibrahim AA, Abdalah MM (2003) Monatsh
Chem 134:1395
11. Amr AE, Abdulla MM (2002) Indian J Heterocycl Chem 12:129
12. Nehad AA, Amr AE, Alhusien AI (2007) Monatsh Chem 138:559
13. Shaban MAE, Morgaan AEA (1999) Adv Heterocycl Chem
75:243
16. Chen H, Shang Z, Chang J (2006) Synth Commun 36:445
17. Guetzoyan LJ, Spooner RA, Lord JM, Roberts LM, Clarkson GJ
(2010) Eur J Med Chem 45:275
18. Nagamatsu T, Yamasaki H, Akiyama T, Hara S, Mori K, Ku-
sakabe H (1999) Synthesis 4:655
19. Khattab AF, El-Essawy FA (2005) J Chem Res 11:736
20. Kumar R, Nair RR, Dhiman SS, Sharma J, Prakash O (2009) Eur
J Med Chem 44:2260
21. Desenko SM, Kolos NN, Tueni M, Orlov VD (1990) Khim
Geterotsikl Soedin 7:938
22. Desenko SM, Orlov VD, Lipson VV (1990) Khim Geterotsikl
Soedin 1638
23. Deshmukh MB, Salunkhe SM, Patil DR, Anbhule PV (2009) Eur
J Med Chem 44:265
24. Shaaban MR (2008) J Fluorine Chem 129:1156
14. Rashad AE, Heikal OA, El-Nezhawy AOH, Abdel-Megeid FME
(2005) Heteroat Chem 16:226
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