Synthesis and reactions of 3-[3-(dimethylamino)propenoyl]-1,7-diphenyl [1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-one

Article abstract of DOI:10.3184/030823408X303989

3-Acetyl-1,7-diphenyl[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-one(1) reacts with N,N-dimethylformamide dimethylacetal (DMFDMA) yielding the enaminone 2. The latter compound reacts with active methylene compounds, hydrazine hydrate, hydroxylamine and some heterocyclic amines to afford trisubstituted pyridine, substituted pyrazole, substituted isoxazole and azolopyrimidines. The antimicrobial activities of the compounds prepared were screened.

Full text of DOI:10.3184/030823408X303989

152 RESEARCH PAPER
MARCH, 152–156
JOURNAL OF CHEMICAL RESEARCH 2008
Synthesis and reactions of 3-[3-(dimethylamino)propenoyl]-1,7-diphenyl
[1,2,4]triazolo[4,3-a]pyrimidin-5(1h)-one
Thoraya A. Farghaly
Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt
3-Acetyl-1,7-diphenyl[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-one (1) reacts with N,N-dimethylformamide dimethylacetal
(DMFDMA) yielding the enaminone 2. The latter compound reacts with active methylene compounds, hydrazine
hydrate, hydroxylamine and some heterocyclic amines to afford trisubstituted pyridine, substituted pyrazole,
substituted isoxazole and azolopyrimidines. The antimicrobial activities of the compounds prepared were screened.
Keywords: enaminone, dimethyformamide dimethylacetal, triazolo[4,3-a] pyrimidin-5(1H)-one, pyridines
The chemistry of enaminones has attracted the interest of
many research groups within the last few decades as they
have proved to be useful organic synthons.1,2 Although
numerous enaminones have been prepared and their reactions
studied, the enaminone 2 namely 3-[3-(dimethylamino)
propenoyl]-1,7-diphenyl[1,2,4]triazolo[4,3-a]pyrimidin-5
(1H)-one has not been reported hitherto. I report here the
synthesis of the new enaminone 2 and the results of its
chemical reactions with active methylene compounds,
hydrazine hydrate, hydroxylamine and some heterocyclic
amines. As shown below, the results of such study indicate that
this new enaminone 2 is an excellent precursor for synthesis
of new functionalised derivatives of 7-phenyl-3-(2-pyridinyl)-
[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-one 5 (Scheme 1). The
latter derivatives are expected to be useful pharmaceuticals
since several 2,3,6-trisubstituted pyridines3,4 and 1,2,4-
triazolo[4,3-a]pyrimidinones5-9 have been reported to exhibit
various biological activites.
Results and discussion
The starting enaminone 2 was prepared in this study by
reaction
of
3-acetyl-1,7-diphenyl[1,2,4]triazolo[4,3-a]
pyrimidin-5(1H)-one 110 with dimethylformamide dimethyl-
acetal (DMFDMA) in refluxing toluene. The spectral data
1
(MS, IR, H NMR) together with the elemental analysis of
the compound 2 are all consistent with the assigned structure
O
COCH
3
N
MeO
Me
Me
CH
N
+
N
MeO
Ph
N
N
Ph
toluene
1
O
O
H
C
C
N
C
H
N(Me)
2
N
+
RCOCH2X
Ph
N
N
3
Ph
2
N(Me)2
R
H
H
X
Het
H
X
O
O
O
Het
R
Me N
2
4
6
NH3
NH3
X
R
X
N
N
R
Het
Het
5
R / X
7
O
N
a
b
c
CH3 / CH3CO
CH3 / C2H5OCO
Ph / C2H5OCO
N
Het =
Ph
N
N
Ph
Scheme 1
* Correspondent. E-mail: thoraya-f@hotmail.com
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JOURNAL OF CHEMICAL RESEARCH 2008 153
H
H
H
C
N(Me)2
H
C
C
O
N
O
N
C
O
N(Me)2
C
C
O
N
N
N
N
N
Ph
N
Ph
Ph
Ph
Z
E
Fig. 1
2. Although compound 2 can has two stereoisomeric
structures, namely the Z and E forms (Fig. 1), it seems to exist
alternating isomeric structure 7 for the isolated products from
reaction of 2 with 3a–c is discarded.
1
predominantly in the E-form based on H NMR data. The
Similarly, the enaminone 2 reacts with active methylene
nitriles 8a–c in refluxing ethanol in the presence of piperidine to
yield products that are identified as the pyridinone derivatives
11a–c, respectively (Sheme 2). The structure assignment of
1H NMR spectrum revealed two doublet signals for olefinic
protons at δ 5.36 and 8.18 having coupling constant value
J = 13 Hz. This value is consistent with the E-isomer and not
the Z-isomer.11
1
the latter products was based on their spectral (IR, H NMR
Reaction of 2 with acetylacetone 3a in refluxing acetic acid
and in the presence of ammonium acetate gave one isolable
product whose mass spectra and IR data are consistent with
either structure 5a or 7a (Scheme 1). However, structure
5a was established for the isolated product on the basis of
its H NMR spectrum. For example, its H NMR spectrum
revealed two singlet signals at δ 2.69 and 2.88 ppm for the
acetyl and methyl protons along with two doublets at δ 8.34
and 8.37 ppm with J = 8.0 Hz. assigned for pyridine H-3 and
H-4 respectively. Such coupling value is characteristic for
pyridines H-3 and H-4 and much higher than that for H-2 and
H-3 (4-6 Hz).12,13
A similar reaction of 2 with each of ethyl acetoacetate 3b
and ethyl benzoyl acetate 3c in acetic acid and in the presence
of ammonium acetate under reflux also afforded the respective
products 5b and 5c. The 1H NMR spectra of the latter products
also revealed in each case two doublet signals with a coupling
constant value J = 8.0 Hz which is typical for pyridine H-3
and H-4.12,13 On the basis of the foregoing data, the other
and MS) and elemental analyses data (see Experimental).
The formation of 11 may proceed via intial Michael addition
of the active methylene compounds 8 across the activated
double bond yielding the adduct 9 followed by cyclisation and
elimination of dimethylamine to give the iminopyran 10 as an
intermediate which isomerises to the corresponding 11 via the
Dimroth type rearrangement.14
1
1
Reaction of enaminone 2 with heterocyclic amines proved
to be excellent synthetic strategy for fused azolopyrimidines.
Thus, reacting 2 with 2-aminoimidazole derivative 12,
3-amino-1,2,4-triazole 13 and 5-aminotetrazole 14 has
afforded imidazo[1,2-a]pyrimidine 15. [1,2,4]-triazolo[4,3-a]
pyrimidine 16 and tetrazolo[1,5-a]pyrimidine 17 derivatives,
respectively (Scheme 3).The structures of the latter products
15–17 were confirmed by their analytical and spectral (IR,
1
MS, H NMR) data (see Experimental). To account for the
formation of such products, it is suggested that reaction
of 2 with each of 12–14 starts with initial Michael addition
of the heterocyclic NH group to the enaminone double
O
C
H
C
O
C
H
N(Me)2
N
NC-CH2-X
N
+
Ph
N
N
8
Ph
2
N(Me)2
H
X
H
H
X
C
Het
O
NH
O
N
Het
9
10
X
8, 11
CN
a
X
C2H5OCO
N
b
c
N
H
Het
O
N
H
O
N
N
11
Het =
N
Ph
N
Ph
Scheme 2
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154 JOURNAL OF CHEMICAL RESEARCH 2008
O
N
O
N
CH
N(Me)2
CH
N
Ph
H
N
2
12
Ph
14
13
CN
N
Me2 N
O
N
N
N
N
Het
N
N
CN
Het
N
N
N
N
Het
17
15
H2N
-HNMe2
-H2O
N
N
Het
N
N
16
NC
N
N
N
N
N
N
N
NH2
N
H
NH2
NC
N
H
NH2
H
14
13
12
O
N
Het =
N
Ph
Ph
N
N
Scheme 3
bond followed by in situ elimination of dimethylamine and
condensation of the heterocyclic NH2 group with the side-
chain carbonyl group to give the isolated products 15–17 as
end products. This suggested reaction mechanism is similar to
literature related reactions.14-17
isoxazole. The alternative product 20 was ruled out as the H-3
proton in 20, would be expected to resonate at higher field,
at around δ 8.3 ppm.18 Also, compound 2 reacts with each of
hydrazine hydrate and guanidine hydrochloride as previously
described to yield 18 and 21, respectively.19-21
Finally, reaction of the enaminone 2 with some nitrogen
nucleophiles were examined. In our hands, the enaminone 2
reacted with hydroxylamine hydrochloride in the presence of
sodium acetate in refluxing ethanol to yield the substituted
isoxazole 19 rather than 20. The structure of 19 was
established based on the 1H NMR spectrum, which showed a
doublet signal at δ 9.15 ppm corresponding to the H-5 of an
Antimicrobial activity
All the products were tested for their antimicrobial activities
against four fungi species namely Aspergillus fumigatus AF,
Penicillium italicum PI, Syncephalastrum racemosum SR
and Candida albican CA as well as four bacteria species
Table 1 Antimicrobial activity of the products
Microorganism/IZC (cm)*
Compound
AF
PI
SR
CA
SA
PA
BS
EC
5a
+
0
+
+
0
+
+
0
0
0
0
0
0
0
0
0
+
+
0
0
+
0
0
0
0
0
0
+
0
0
0
5b
0
5c
0
+ +
+
0
+
0
+
11a
11b
11c
15
+
+
0
0
+
+
+
0
+
0
+
0
+
0
+
0
+
+
+
0
+
+
0
+
18
+
+
0
0
+
19
+ +
0
+ +
+ +
+ + +
+
0
+ + +
0
+ +
0
+ + +
+
21
0
Teb
Chb
+ + +
+ +
+ +
+ + +
+ + +
+ +
*IZD, inhibition zone diameter: + + + , inhibition value 1.1–1.5 cm; + + , inhibition value 0.6–1.0 cm, + , inhibition value 0.1–0.5 cm;
0, no inhibition detected.
a50 ml solution in DMF, whose concentration of 5 mg/ml was tested.
bTe = Terbinafin as standard antifungal agent and Ch = Chloroamphenicol as the standard antibacterial agent
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JOURNAL OF CHEMICAL RESEARCH 2008 155
H
C
O
N
O
N
N(Me)2
C
H
N
Ph
N
NH
NH2NH2.H2O
2
Ph
H2N
C
NH2
NH2OH
N
N
Het
18
N
H
Het
N
NH2
21
O
N
Het
N
Het
O
19
20
O
N
N
Het =
N
Ph
N
Ph
Scheme 4
compounds 3 (5 mmole) were added. The reaction mixture was heated
with stirring under reflux for 3–4 h, and the solvent was evaporated
under reduced pressure. The residuel solid formed was filtered and
crystallised from ethanol to give products 5a–c.
3-(6-Acetyl-5-methyl-pyridin-2-yl)-1,7-diphenyl[1,2,4]triazolo
[4,3-a]pyrimidin-5(1H)-one (5a): White crystals (1.68 g, 80%).
m.p. 220°C. IR: νmax 1701, 1681 cm-1. NMR (CDCl3): δH 2.69 (s,
3H, CH3), 2.88 (s, 3H, CH3), 6.59 (s, 1H, ArH), 7.27–8.15 (m, 10H,
ArH), 8.34 (d, J = 8 Hz, 2H, ArH), 8.37 (d, J = 8 Hz, 2H, ArH). MS:
m/z (%) 422 (M+ + 1, 13), 421(M+, 55), 420(47), 236 (14), 129 (35),
109 (25), 105 (12), 91(60), 84(44), 77(29), 57(100), 55(90). Anal.
Calcd for C25H19N5O2 (421. 46) C, 71.25; H, 4.54; N, 16.62. Found:
C, 71.03; H, 4.25; N, 16.40%.
3-(6-Ethoxycarbonyl-5-methyl-pyridin-2-yl)-1,7-diphenyl[1,2,4]
triazolo[4,3-a]pyrimidin-5(1H)-one (5b): White solid (1.65 g, 73%)
m.p. 180°C. IR: νmax 1732, 1697 cm-1. NMR (CDCl3): δH 1.45 (t,
J = 7 Hz, 3H, CH3), 2.97 (s, 3H, CH3), 4.44 (q, J = 7 Hz, 2H, CH2),
6.59 (s, 1H, ArH), 7.27–7.81 and 8.34–8.40 (m, 10H, ArH), 7.78 (d,
J = 8 Hz, 2H, ArH), 8.08 (d, J = 8 Hz, 2H, ArH). MS: m/z (%) 452
(M+ + 1, 4), 451 (M+, 12), 368 (39), 313 (18), 288 (14), 236 (31), 183
(18), 157 (15), 129 (37), 111 (38), 98 (72), 91 (13), 83 (100), 77 (13),
55 (38). Anal. Calcd for C26H21N5O3 (451.49) C, 69.17; H, 4.69; N,
15.51. Found: C, 69.43; H, 4.43; N, 15.21%.
3-(6-Ethoxycarbonyl-5-phenyl-pyridin-2-yl)-1,7-diphenyl[1,2,4]
triazolo[4,3-a] pyrimidin-5(1H)-one (5c): Yellow crystals (2.0 g,
79%) m.p. 240°C. IR: νmax 1720, 1685 cm-1. NMR (DMSO-d6): δH
1.08 (t, J = 7 Hz, 3H, CH3), 4.19 (q, J = 7 Hz, 2H, CH2), 6.70 (s, 1H,
ArH), 7.48–7.70 (m, 15H, ArH), 8.01 (d, J = 8 Hz, 2H, ArH), 8.37
(d, J = 8 Hz, 2H, ArH). MS: m/z (%) 515 (M+ + 2, 25), 514 (M+ +
1, 90), 513 (M+, 100), 512 (59), 485 (48), 484 (69), 468 (12), 207
(18), 179 (13), 128 (14), 103 (33), 91 (61), 77 (80). Anal. Calcd for
C31H23N5O3 (513.56) C, 72.50; H, 4.51; N, 13.64. Found: C, 72.24;
H, 4.19; N, 13.38%.
3-(5-Cyano-6-oxo-1,6-dihydropyridin-2-yl)-1,7-diphenyl[1,2,4]
triazolo[4,3-a]pyrimidin-5(1H)-one (11a): To a solution of enaminone
2 (1.93 g, 5 mmole) in ethanol (30 ml) was added malononitrile
(0.17 g, 5 mmole) and few drops of piperidine. The reaction mixture
was heated on a water bath at 30–40°C for 24 h, then left to cool.
The solid so formed was collected by filtration, washed with ethanol
and crystallised from dioxane to give red solid (1.42 g, 70%) yield
m.p > 300°C. IR: νmax 3386, 2221 1689, 1651 cm-1. NMR (CDCl3):
δH 6.60 (s, 1H, ArH), 7.27–7.92 (m, 10H, ArH), 8.19 (d, J = 8 Hz,
2H, ArH), 8.29 (d, J = 8 Hz, 2H, ArH), 13.90 (s, 1H, NH). MS: m/z
(%) 408 (M+ + 2, 24), 407 (M+ + 1, 22), 406 (M+, 44), 288 (72), 287
(88), 129 (64), 117 (20), 103 (62), 91 (78), 77 (100). Anal. Calcd for
C23H14N6O2 (406.41) C, 67.98; H, 3.47; N, 20.68. Found: C, 67.62;
H, 3.30; N, 20.45%.
namely Staphylococcus aureus SA, Pseudomonas aeruginosa
PA, Bacillus subtilis BS and Escherichia coli EC. The
organisms were tested against the activity of solutions of three
concentrations namely 1.0, 2.5 and 5 μg/ml of each compound
and using inhibition zone diameter in cm as criterion for
the antimicrobial activity. Chloroamphenicol as standard
antibacterial agent and Terbinafin as standard antifungal
agent were used as references to evaluate the potency of the
tested compounds under the same conditions. The results
obtained using solutions having 5 μg/ml of each compound
are summarised in Table 1. Such results showed that the
compound 19 exhibited the moderate degree of inhibition
against the test fungus species AF. The compounds 5c, 19 and
21 exhibited the moderate degree of inhibition against the test
fungus species PI. Furthermore, compound 19 inhibited the
bacteria species SA and BS. All other compounds exhibited
low or no activity against the microrganisms tested.
Experimental
All melting points were determined on an electrothermal Gallenkamp
apparatus and are uncorrected. Solvents were generally distilled and
dried by standard literature procedures prior to use. The IR spectra
were measured on a Pye-Unicam SP300 instrument in potassium
bromide discs. The 1H NMR spectra were recorded on a Varian
Mercury VXR-300 spectrometer (300 MHz for 1H NMR) and the
chemical shifts were related to that of the solvent DMSO-d6. The
mass spectra were recorded on a GCMS-Q1000-EX Shimadzu and
GCMS 5988-A HP spectrometers, the ionising voltage was 70 eV.
Elemental analyses were carried out by the Microanalytical Centre of
Cairo University, Giza, Egypt. 3-acetyl-1,7-diphenyl[1,2,4]triazolo[4,
3-a]pyrimidin-5(1H)-one 110 was prepared by the literature method.
3-[3-(Dimethylamino)propenoyl]-1,7-diphenyl[1,2,4]triazolo[4,3-a]
pyrimidin-5(1H)-one (2): A mixture of compound
1 (6.6 g,
20 mmole) and DMFDMA (2.68 g, 20 mmole) in dry toluene
(20 ml) was refluxed for 6 h. then left to cool to room temperature.
The precipitate was filtered off, washed with ether, dried and
recrystallised from ethanol to give orange crystals (6.16 g, 80%),
m.p. 212°C. IR: νmax 1685, 1650 cm-1. NMR (CDCl3): δH 2.91 (s, 3H,
N–CH3), 3.06 (s, 3H, N–CH3), 5.36 (d, J = 13 Hz, 2H, =CH), 6.63 (s,
1H, ArH), 7.42–8.17 (m, 10H, ArH), 8.18 (d, J = 13 Hz, 2H, =CH).
MS: m/z (%) 385 (M+, 10), 367 (22), 366 (12), 105 (3), 98 (100), 91
(3), 89 (7), 77 (26), 70 (16). Anal. Calcd for C22H19N5O2 (385.43) C,
68.56; H, 4.97; N, 18.17. Found: C, 68.38; H, 4.69; N, 18.00%.
General procedure for the preparation of 3-(5,6-disubstitutedpyridin-
2-yl)-1,7-diphenyl[1,2,4]triazolo[4,3-a] pyrimidin-5(1H)-one (5a–c)
To a solution of enaminone 2 (1.93 g, 5 mmole,) and ammonium
acetate (0.5 g) in acetic acid (10 ml), the appropriate active methylene
General procedure of preparation of compounds (11b–c)
To a solution of enaminone 2 (1.93 g, 5 mmole) and active methylene
nitrile compound 8 (0.005 mole) in toluene (30 ml) was added few
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156 JOURNAL OF CHEMICAL RESEARCH 2008
drops of piperidine. The reaction mixture was refluxed for 6 h and
the solvent was removed under vacuum. The solid so formed was
collected by filtration, washed with ethanol and crystallised from
ethanol to give compounds 11b–c.
was collected by filtration and recrystallised from ethanol/dioxane to
yield white crystals (1.46 g, 82%) m.p. > 300°C. IR: νmax 1701 cm-1.
NMR (DMSO-d6): δH 6.21 (d, J = 8 Hz, 2H, ArH), 6.57 (s, 1H, ArH),
7.41–8.14 (m, 10H, ArH), 9.15 (d, J = 8 Hz, 2H, ArH). MS: m/z 355
(M+, 41), 353 (100), 242 (22), 90 (76), 89 (25),77 (88). Anal. Calcd
for C20H13N5O2 (355.36) C, 67.60; H, 3.69; N, 19.71. Found: C,
67.40; H, 3.80; N, 19.53%.
3-(5-Ethoxycarbonyl-6-oxo-1,6-dihydropyridin-2-yl)-1,7-diphen
yl[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-one (11b): Yellow solid
(1.59 g, 70%) m.p. 232°C. IR: νmax 3421, 1716, 1651, 1612 cm-1.
NMR (CDCl3): δH 1.39 (t, J = 7 Hz, 3H, CH3), 4.34 (q, J = 7 Hz,
2H, CH2), 6.85 (s, 1H, ArH), 7.12 (d, J = 9 Hz, 2H, ArH), 7.16–8.32
(m, 10H, ArH), 8.59 (d, J = 9 Hz, 2H, ArH), 14.25 (s, 1H, NH).
MS: m/z (%) 455 (M+ + 2, 22), 454 (M+ + 1, 65), 453 (M+, 88), 406
(12), 380 (100), 353 (12), 287 (11), 145 (13), 129 (28), 120 (17),
116 (13), 103 (18), 91 (27), 77 (66). Anal. Calcd for C25H19N5O4
(453.46) C, 66.22; H, 4.22; N, 15.44. Found: C, 66.00; H, 4.25;
N, 15.24%.
3-(5-(2-benzimidazolyl)-6-oxo-1,6-dihydropyridin-2-yl)-1,7-diph
enyl[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-one (11c): Yellow solid
(2.04 g, 82%) m.p. 238°C; IR: νmax 3421, 3058 1691, cm-1. NMR
(CDCl3): δH 6.63 (s, 1H, ArH), 7.44–8.15 (m, 14H, ArH), 8.16 (d,
J = 8 Hz, 2H, ArH), 8.23 (d, J = 8 Hz, 2H, ArH), 11.0 (s, 1H, NH),
13.82 (s, 1H, NH). MS: m/z (%) 497 (M+, 14), 370 (32), 329 (60), 247
(34), 171 (21), 162 (21), 110 (63), 91 (24), 77 (100). Anal. Calcd for
C29H19N7O2 (497.52) C, 70.01; H, 3.85; N, 19.71. Found: C, 70.10;
H, 3.63; N, 19.50%.
3-(2-Aminopyrimidin-4-yl)-1,7-diphenyl[1,2,4]triazolo[4,3-a]pyrimidin-
5(1H)-one (21): To a mixture of enaminone 2 (1.68 g, 5 mmole) and
guanidine hydrochloride (0.5 g, 6 mmole) in absolute ethanol (30 ml),
anhydrous potassium carbonate (40 mmole) was added. The reaction
mixture was refluxed for 10 hrs., allowed to cool to room temperature
and then diluted the solid product was filtered off washed with water,
dried and recrystallised from ethanol/dioxane to give orange solid
(g, 50%) m.p. 126°C. IR: νmax 3398, 1693 cm-1. NMR (DMSO-d6): δH
6.25 (s, 2H, NH2), 6.53 (s, 1H, ArH), 7.02–8.11 (m, 10H, ArH), 7.41
(d, J = 8 Hz, 2H, ArH), 7.96 (d, J = 8 Hz, 2H, ArH). MS: m/z 382 (M+
+ 1, 5), 381 (M+, 5), 380 (40), 287 (24), 134 (52), 105 (17), 94 (100),
91 (32), 77 (84). Anal. Calcd for C21H15N7O (381.40) C, 66.13; H,
3.96; N, 25.71. Found: C, 66.43; H, 3.89; N, 25.50%.
Antimicrobial assay
Cultures of four fungi species namely Aspergillus fumigatus AF,
Penicillium italicum PI, Syncephalastrum racemosum SR and Candida
albican CA as well as four bacteria species namely Staphylococcus
aureus SA, Pseudomonas aeruginosa PA, Bacillus subtilus BS and
Escherichia coli EC were used to investigate the antimicrobial activity
of the compounds 5a–c, 11a–c, 15–18. The fungicide Terbinafin and
the bactericide Chloroamphenicol were used as standard under the
same conditions. The antimicrobial activity was assayed biologically
using the diffusion plate technique as previously described.22
General procedure of preparation of compounds (15–17)
A mixture of enaminone 2 (1.93 g, 5 mmole) and the appropriate
heterocyclic amines 12–14 (6 mmole) in dry toluene (20 ml)
was refluxed for 10 h then left to cool to room temperature.
The solvent was evaporated under vacuum then the solid so formed
was filtered off, washed with ethanol, dried and recrystallised from
the appropriated solvent to give products 15–17.
3-(2,3-Dicyanoimidazo[1,2-a]pyrimidin-7-yl)-1,7-diphenyl[1,2,4]
triazolo[4,3-a]pyrimidin-5(1H)-one (15): Orange solid (1.54 g,
72%) m.p. 222°C (dioxane). IR: νmax 2183, 2144, 1701 cm-1. NMR
(CDCl3): δH 6.60 (s, 1H, ArH), 7.01–7.32 (m, 10H, ArH), 7.42 (d,
J = 7 Hz, 2H, ArH), 7.84 (d, J = 7 Hz, 2H, ArH). MS: m/z (%) 457
(M+ + 2, 5), 456 (M+ + 1, 3), 455 (M+, 100), 454 (42), 352 (16),
287 (32),145 (14), 155 (41), 129 (13), 116 (25), 103 (21), 91 (61),
77 (80). Anal. Calcd for C25H13N9O (455.44) C, 65.93; H, 2.88; N,
27.68. Found: C, 65.85; H, 3.08; N, 27.46%.
3-([1,2,4]Triazolo[1,5-a]pyrimidine-7-yl)-1,7-diphenyl[1,2,4]triazolo
[4,3-a]pyrimidin-5(1H)-one (16): Yellow crystals (1.50 g, 74%)
m.p. 260°C (DMF); IR: νmax 1693 cm-1. NMR (CDCl3): δH 6.45 (s,
1H, ArH), 7.27–8.02 (m, 10H, ArH), 7.86 (d, J = 9 Hz, 2H, ArH),
8.11 (d, J = 9 Hz, 2H, ArH), 8.93 (s, 1H, ArH). MS: m/z (%) 408 (M+
+ 2, 18), 407 (M+ + 1, 65), 406 (M+, 100), 405 (79), 289 (33), 288
(59), 233 (33), 136 (26), 129 (21), 103 (57), 91 (82), 77 (80). Anal.
Calcd for C22H14N8O (406.41) C, 65.02; H, 3.47; N, 27.57. Found: C,
64.93; H, 3.22; N, 27.34%.
3-[Tetrazolo[1,5-a]pyrimidine-7-yl]-1,7-diphenyl[1,2,4]triazolo[
4,3-a]pyrimidin-5(1H)-one (17): White crystals (1.59 g, 78%) m.p.
204°C; IR: νmax 1689 cm-1. NMR (CDCl3): δH 6.63 (s, 1H, ArH),
7.32–7.85 (m, 10H, ArH), 7.91 (d, J = 8 Hz, 2H, ArH), 8.10 (d,
J = 8 Hz, 2H, ArH). MS: m/z (%) 408 (M+ + 1, 4), 407 (M+, 24), 288
(12), 105 (83), 91 (14), 77 (100). Anal. Calcd for C21H13N9O (407.40)
C, 61.91; H, 3.22; N, 30.94. Found: C, 61.83; H, 3.00; N, 30.63%.
3-[Pyrazol-3-yl]-1,7-diphenyl[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)
-one (18): A mixture of hydrazine hydrate (6 mmole) and enaminone
2 (1.68 g, 5 mmole) in absolute ethanol (30 ml) was refluxed for 2 h,
then left to cool to room temperature. The solid formed was filtered
off, washed with ethanol, dried and recrystallised from ethanol to
give product 18 (1.5 g, 85%) m.p. 170°C. IR: νmax 3116, 1685 cm-1.
NMR (DMSO-d6): δH 6.66 (s, 1H, ArH), 7.44–7.53 and 7.64–8.23
(m, 10H, ArH), 7.54 (d, J = 8 Hz, 2H, H-pyrazole), 8.25 (d, J = 8 Hz,
2H, H-pyrazole), 9.39 (s, 1H, NH). MS: m/z 354 (M+, 41), 353(100),
243(44), 235 (12), 230(41), 181(24), 1733(18), 156(18), 77(49). Anal.
Calcd for C20H14N6O (354.37) C, 67.79; H, 3.98; N, 23.72. Found: C,
67.66; H, 3.86; N, 23.39%.
Received 19 January 2008; accepted 14 March 2008
Paper 08/5049
doi: 10.3184/030823408X303989
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PAPER: 08/5049