Studies with 2-arylhydrazononitriles: Further investigations on the utility of 2-arylhydrazononitriles as precursors to 1,2,3-triazole amines

Article abstract of DOI:10.3184/030823407X244869

3-Oxo-2-arylhydrazonobutanenitriles react with hydroxylamine hydrochloride in ethanolic sodium acetate to yield either amidoximes or isoxazolamines depending on the nature of the substituent. The amidoximes cyclise in refluxing DMF containing piperidine t

Full text of DOI:10.3184/030823407X244869

JOURNAL OF CHEMICAL RESEARCH 2007
SEPTEMBER, 515–518
RESEARCH PAPER 515
Studies with 2-arylhydrazononitriles: further investigations on the utility
of 2-arylhydrazononitriles as precursors to 1,2,3-triazole amines
Saleh Mohammed Al-Mousawi*, Moustafa Sherief Moustafa and Mohamed Hilmy Elnagdi
Department of Chemistry, Faculty of Science, University of Kuwait, Safat 13060, PO Box 5969, Kuwait
3-Oxo-2-arylhydrazonobutanenitriles react with hydroxylamine hydrochloride in ethanolic sodium acetate to
yield either amidoximes or isoxazolamines depending on the nature of the substituent. The amidoximes cyclise
in refluxing DMF containing piperidine to form 2-aryl-1,2,3-triazol-5-amines. The isoxazolamines rearranged into
1,2,3-triazolamines on refluxing in DMF. Amidoxime 2c cyclised in acetic anhydride to give 2-arylhydrazono-1,2,4-
oxadiazole 9c, which rearranged to acetylamino-1,2,3-triazole 8c. The prepared acetyl-1,2,3-triazolamines 8b,c were
utilised as precursors to triazolopyridines and pyrazolyltriazoles.
Keywords: arylhydrazones, amidoximes, ketonitriles, isoxazoleamines, pyrazoles, 1,2,3-triazoleamines, fused 1,2,3-triazoles,
fused pyridines
The synthetic potentialities of 2-arylhydrazononitriles have
recently been reviewed.1 Elnagdi et al. showed that these
readily obtainable2-4 versatile starting materials are excellent
precursors to pyrazolamines, 1,2,4-triazolamines,5 1,2,3-
triazolamines,6 isoxazol-3-amines7 and pyridazin-6-imines.8
Recently Elnagdi et al. have reported that 2-phenylhydrazono-
3-oxobutanenitrile 1a reacted with hydroxylamine
hydrochloride in ethanolic sodium acetate to yield amidoxime
2a that cyclised readily into 4-acetyl-2-phenyl-1,2,3-triazol-5-
amine 3a upon reflux in DMF in presence of piperidine.9
amidoxime 2b would cyclise readily to 3b in a way similar
to that reported recently from our laboratories.10 However,
13C NMR of the reaction product indicated that this was not
the case, as it indicated the absence of the carbonyl carbon
in the range d = 180–200 ppm. We therefore considered the
formation of isomeric isoxazoles 4b and/or 5b. While 4b
can be produced via cyclisation of the initially formed 2b,
formation of 5b can take place only via intermediacy of the
initial product of condensation of the keto carbonyl of 1b
with hydroxylamine, yielding 6b, that could then cyclise to
5b (Scheme 1).
The subsequent chemical behaviour of the reaction product
led us to conclude that 4b is the correct structure. Thus, when it
was heated in DMF in the presence of piperidine it rearranged
readily into 3b, which reacted readily with malononitrile to
yield the triazolo[4,5-b]pyridine 7b (Scheme 1).
Results and discussion
As part of this work, we subjected 1b to hydroxylamine
hydrochloride in ethanolic sodium acetate. Unexpectedly,
a condensation product with elimination of water was
obtained. We had expected that an intermediately formed
OH
O
N
Me
NH2
N
NH
Ar
ii
∆,
reflux
2a,c
NH2
N
NC
O
MeCO
NH2
O
Me
Ar
N
Me
CN
i
iii
Me
ii
N
N
N
N
NH2
N
N
HN
Ar
N
N
Ar
N
4b
3a-c
Ar
7b,c
1a-c
N
OH
N
Me
N
O
CN
Me
NH2
N
N
NH
Ar
Ar
5b
Scheme 1 Reagents: i, NH2OH.HCl, EtOH, NaOAc; ii, DMF/piperidine; iii, CH2(CN)2, EtOH
* Correspondent. E-mail: salehalmousawi@hotmail.com
6b
PAPER: 07/4783

516 JOURNAL OF CHEMICAL RESEARCH 2007
Me
OH
NHCOCH3
NH2
O
N
MeCO
MeCO
N
O
O
(ii)
iii
i
ii
Me
NH2
N
Me
N
N
N
N
N
N
N
N
NH
Ar
NH
Ar
Ar
Ar
3c
2c
8c
9c
Ar = p-ClC6H4
Scheme 2 Reagents: i, Ac2O; ii, reflux, DMF; iii, AcOH/Ac2O.
Me2N
O
In an attempt to cyclise 2c to the 1,2,3-triazole derivative 3c via
refluxing in acetic anhydride, an acylated product was formed.
Initially we thought that this product is acetyl derivatives of
3c (compounds 8c). However, 8c proved to be different from
the product of reaction 2c with acetic anhydride. The latter
was thus assigned structure 9c. Heating 9c in DMF gives 3c.
We believe that initially a Katritzky–Boulton11 rearrangement
of 9c into 8c occurred and that 8c was then deacetylated under
the reaction conditions.
NHCOMe
i
ii
N
N
8b,c
3b,c
N
Ar
10b,c
b, Ar = p-MeOC6H4, Y = H
c, Ar = p-ClC6H4, Y = Ac
We have investigated the potential utility of 8b,c
for synthesis of azolyl-1,2,3-triazoles as well as 1,2,3-
triazoloazines. Refluxing 8b,c with dimethylformamide
dimethylacetal (DMFDMA) afforded the trans-enaminones
10b,c based on their H NMR. Thus, the H NMR of 10b
revealed two olefinic protons at d = 5.85 and 7.13 ppm
with the coupling constant J = 12 Hz. A smaller J would be
expected for cis olefinic protons.
Compounds 10b,c were refluxed with hydrazine hydrate in
ethanol to yield the pyrazolyl-1,2,3-triazole 11b,c. Refluxing
10b in DMF in the presence of piperidine gave 1,2,3-triazolo-
[4,5-b]pyridine 12b (Scheme 3).
iv
iii
H
N
N
O
NH
1
1
NH-Y
N
N
N
N
N
N
Ar
Ar
11b,c
12b
Scheme 3 Reagents: i, Ac2O/AcOH; ii, DMFDMA, xylene;
iii, N2H4.H2O/EtOH; iv, DMF, piperidine.
Coupling of 10b,c with benzenediazonium chloride gave
15b,c via intermediacy of the nonisolable 13b,c, or their
hydrolysis products 14b,c. Enaminones are known to react
readily with aromatic diazonium salts to yield arylazo (or
arylhydrazono) derivatives.12 This is thus a further application
of this reaction.
Although 15b,c can also, at least in theory, exist as 16 or
17 or other tautomers, 13C NMR as well as NOE difference
experiment supported the proposed hydrazone structure 15b,c
(Scheme 4).
To our knowledge, this is the first reported rearrangement
of arylazoisoxazol-3-amines into 1,2,3-triazole derivatives.
In contrast to 1b, compound 1c reacted with hydroxylamine
hydrochloride in ethanolic sodium acetate yielding 2c that
cyclised into 3c on refluxing in DMF in the presence of
piperidine. The latter also condensed with malononitrile,
yielding 7c (Scheme 1).
PhN=N
NMe2
O
O
N
COCH3
NHCOMe
i
N
N
10b,c
Ph
N
N
N
N
N
N
Ar
Ar
13b,c
14b,c
ii
PhN=N
O
PhN=N
PhNH-N
O
HO
N
NH
N
N
N
N
N
N
N
N
N
Ar
16
N
Ar
Ar
15b,c
17
Scheme 4 Reagents: i, PhN2+Cl-; ii, (deacetylation).
PAPER: 07/4783

JOURNAL OF CHEMICAL RESEARCH 2007 517
2H, NH2, D2O-exchanged), 6.9 (d, 2H, J = 8 Hz, Ar–H), 7.7 (d, 2H,
J = 8 Hz, Ar–H); δC 171.6, 162.2, 156.5, 147.2, 125.4 (2CH), 118.2,
115.65 (2CH), 56.22 (CH3), 11.9 (CH3). MS: m/z (%) 232 (M+, 95),
221 (30), 189 (20), 147 (30), 135 (25), 121 (80), 107 (40), 73 (35), 55
(35). Anal. Calcd for C11H12N4O2 (232.2): C, 56.9; H, 5.2; N, 24.1.
Found C, 56.8; H, 5.1; N, 23.8%.
Experimental
IR spectra were recorded in KBr and were determined on a Perkin-
Elmer 2000 FT-IR system. NMR spectra were determined on a
1
Bruker DPX spectrometer, at 400 MHz for H NMR and 100 MHz
for 13C NMR, in CDCl3 or DMSO-d6 as solvent and TMS as internal
standard; chemical shifts are reported in d (ppm). Mass spectra were
measured on VG Autospec QMS 30 and MS 9 (AEI) spectrometers,
with EI 70 eV. Elemental analyses were measured using a LEO
CHNS-932 Elemental Analyser in the Analytical Laboratory of
Kuwait University.
1-[5-Amino-2-(4-methoxyphenyl)-2H-1,2,3-triazol-4-yl]ethanone (3b)
Compound 4b (2.32 g, 0.01 mol) in N,N-dimethylformamide (10 ml)
containing a few drops of piperidine was heated under reflux for 4 h,
cooled, and then poured into ice-water. The solid which separated was
collected by filtration and crystallised from ethanol to give yellow
plates(yield 75%), m.p. 143–145°C. IR: νmax 3452, 3355 (NH2),
1660 cm-1 (CO). NMR: δH (CDCl3) 2.6 (s, 3H, CH3), 3.8 (s, 3H,
CH3), 6.3 (s, 2H, NH2, D2O-exchanged), 7.1 (d, 2H, J = 8 Hz, Ar–H),
8.8 (d, 2H, J = 8 Hz, Ar–H); δC (DMSO-d6) 193.7 (CO), 159.7,
155.3, 133.4, 132.3, 120.7 (2CH), 115.7 (2CH), 80.1, 56.5 (CH3),
27.6 (CH3). MS: m/z (%) 232 (M+, 100), 189 (15), 148 (15), 121 (85).
Anal. Calcd for C11H12N4O2 (232.2): C, 56.9; H, 5.2; N, 24.1. Found
C, 57.1; H, 5.2; N, 24.1%.
Synthesis of hydrazono-nitriles 1b,c: general procedure
A cold solution of aryldiazonium salt (0.01 mol) was prepared by
adding sodium nitrite (0.7 g) in H2O (5 ml) to a cold solution of an
arylamine hydrochloride (0.01 mol of arylamine in 5 ml concentrated
HC1) with stirring. The resulting aryldiazonium salt solution was
then dropped into a cold solution of 3-aminocrotononitrile (0.82 g,
0.01 mol) in ethanol (10 ml) and subsequently sodium acetate (2 g)
was added. The reaction mixture was then kept at room temperature
for 1 h. The resulting solid product which separated was filtered off
and dissolved in acetic acid (20 ml). Concentrated hydrochloric acid
(12 ml) was added, and the mixture was refluxed for 15 min, allowed
to cool, and then poured into ice-water. A yellow solid was obtained,
which was isolated and recrystallised from ethanol.
Synthesis of triazolopyridines 7b,c, general procedure
Equimolecular amounts of compound 3b,c (0.01 mol) and
malononitrile (0.66 g, 0.01 mol) in N,N-dimethylformamide (10 ml)
were treated with a few drops of piperidine. The reaction mixture
was heated to reflux for 3 h. After cooling, the mixture was poured
onto ice-water. The solid, so formed, was collected by filtration and
crystallised from ethanol.
2-[2-(4-Methoxyphenyl)hydrazono]-3-oxobutanenitrile
(1b):
Yellow plates (90%), m.p. 130–132°C. IR: νmax 3198 (NH), 2213
(CN), 1667 cm-1 (CO). NMR: δH (CDCl3) 2.5 (s, 3H, CH3), 3.8 (s,
3H, OCH3), 6.9 (d, 2H, J = 8 Hz, Ar–H), 7.3 (d, 2H, J = 8 Hz, Ar–
H), 9.6 (s, 1H, NH, D2O exchangeable); δC (DMSO-d6) 193.5 (CO),
157.9, 136.4, 130.3, 119.1 (2CH), 115.6 (2CH), 112.2, 56.2, 25.5
(CH3). MS: m/z (%) 217 (M+, 98), 122 (65), 107 (80), 77 (50). Anal.
Calcd for C11H11N3O2 (217.2): C, 60.8; H, 5.1; N, 19.3. Found: C,
60.6; H, 4.9; N, 19.3%.
2-[2-(4-Chlorophenyl)hydrazono]-3-oxobutanenitrile (1c): Yellow
plates (82%), m.p. 220–222°C. IR (KBr): νmax 3236 (NH), 2211 (CN),
1667 cm-1 (CO). NMR (DMSO-d6): δH 2.4 (s, 3H, CH3), 7.4 (d, 2H,
J = 8 Hz, Ar–H), 7.5 (d, 2H, J = 8 Hz, Ar–H), 12.3 (s, 1H, NH, D2O-
exchangeable); δC 193.5 (CO), 141.9, 130.3 (2CH), 129.9, 118.8
(2CH), 115.2, 111.8 56.2, 25.5 (CH3). MS: m/z (%) 221 (M+, 100),
139 (40), 111 (85), 75 (15). Anal. Calcd for C10H8ClN3O (221.6): C,
54.1; H, 3.6; N, 18.9. Found C, 54.0; H, 3.6; N, 19.0%.
2-[2-(4-Chlorophenyl)hydrazono]-N-hydroxy-3-oxobutanamidine (2c)
The nitrile 1c (2.21 g, 0.01 mol), hydroxylamine hydrochloride
(0.69 g; 0.01 mol), and sodium acetate (0.82 g, 0.01 mol) in ethanol
(20 ml) were refluxed for 4 h. After cooling, the mixture was poured
onto ice-water. The solid which separated was collected by filtration
and crystallised from ethanol to give yellow needles (yield 75%),
m.p. 207–208°C. IR: νmax 3478 (OH), 3340, 3285 (NH2), 3155 (NH),
1697 cm-1 (CO). NMR: δH (CDCl3) 2.5 (s, 3H, CH3), 6.1 (br, 1H,
OH, D2O-exchanged), 6.5 (br, 2H, NH2, D2O-exchanged), 7.2 (d, 2H,
J = 8 Hz, Ar–H) 7.3 (d, 2H, J = 8 Hz, Ar–H), 13.4 (s, 1H, NH, D2O-
exchanged); δC (DMSO-d6) 199.4 (CO), 152.1, 142.4, 130.5 (2CH),
128.4, 127.8, 117.1 (2CH), 27.4 (CH3). MS: m/z (%) 254 (M+, 95),
237 (80), 221 (40), 195 (10), 141 (20), 127 (60), 111 (40), 90 (15), 69
(45). Anal. Calcd for C10H11ClN4O2 (254.6): C, 47.1; H, 4.3; N, 22.0.
Found C, 47.5; H, 4.2; N, 22.0%.
5-Amino-2-(4-methoxyphenyl)-7-methyl-2H-[1,2,3]triazolo[4,5-
b]pyridine-6-carbonitrile (7b): Yellow fibrous crystals (yield 62%),
m.p. 277–278°C. IR: νmax 3469, 3366 (NH2), 2218 cm-1 (CN). NMR:
δH (CDCl3) 2.9 (s, 3H, CH3), 3.9 (s, 3H, CH3), 5.4 (s, 2H, NH2, D2O-
exchanged), 7.1 (d, 2H, J = 8 Hz, Ar–H), 8.2 (d, 2H, J = 8 Hz, Ar–H);
δC (DMSO-d6) 160.9, 159.3, 157.0, 149.2, 133.7, 133.4, 122.2 (2CH),
116.3, 115.9 (2CH), 97.5, 56.67 (OCH3), 17.17 (CH3). MS: m/z (%)
280 (M+, 80), 265 (20), 232 (40), 221 (50), 207 (20), 147 (20), 121
(30), 97 (40), 81 (50), 69 (95), 57 (80). Anal. Calcd for C14H12N6O
(280.3): C, 59.9; H, 4.3; N, 29.9. Found C, 59.9; H, 4.3; N, 29.5%.
5-Amino-2-(4-chlorophenyl)-7-methyl-2H-[1,2,3]triazolo[4,5-
b]pyridine-6-carbonitrile (7c): Yellow crystals (yield 58%), m.p.
289–290°C. IR: νmax 3390, 3386 (NH2), 2230 cm-1 (CN). NMR: δH
(CDCl3) 2.9 (s, 3H, CH3), 5.5 (s, 2H, NH2, D2O-exchanged), 7.5 (d,
2H, J = 8 Hz, Ar–H), 8.2 (d, 2H, J = 8 Hz, Ar–H). δC (DMSO-d6)
159.4, 157.1, 149.5, 138.9, 134.6, 134.1, 130.8 (2CH), 122.2 (2CH),
116.1, 98.6, 17.2 (CH3). MS: m/z (%) 284 (M+, 65), 235 (95), 218
(50), 193 (15), 138 (30), 124 (75), 110 (80), 90 (30), 69 (35). Anal.
Calcd for C13H9ClN6 (284.7): C, 54.8; H, 3.1; N, 29.5. Found C,
54.6; H, 3.2; N, 29.2%.
Synthesis of triazoles 8b,c: general procedure
Equimolar amounts of amine 3b,c (0.01 mol) and acetic anhydride
(1.02 g, 0.01 mol) in glacial acetic acid (20 ml) were heated to reflux
for 2 h. After cooling, the reaction mixture was poured into ice-water.
The solid so formed was collected by filtration and crystallised from
petroleum ether (b.p. 60–80°C) to give yellow crystals.
N-[5-Acetyl-2-(4-methoxyphenyl)-2H-1,2,3-triazol-4-yl]acetamide
(8b): Yellow granules (70%), m.p. 126–127°C. IR: νmax 3321 (NH),
1716 (CO), 1670 cm-1 (CO). NMR (DMSO-d6): δH 2.1 (s, 3H, CH3),
2.5 (s, 3H, CH3), 3.38 (s, 3H, OCH3), 7.1 (d, 2H, J = 8 Hz, Ar–H), 7.9
(d, 2H, J = 8 Hz, Ar–H), 10.1 (br, 1H, NH, D2O-exchanged); δC 192
(CO), 169.4 (CO), 145.4, 138.9, 133.8, 130.9 (2CH), 130.7, 121.5
(2CH), 56.8 (OCH3), 28.8 (CH3), 24.2 (CH3). MS: m/z (%) 274 (M+,
60), 232 (100), 217 (10), 189 (25), 135 (15), 121 (40), 107 (25), 92
(15), 77 (15), 64 (10). Anal. Calcd for C13H14N4O3 (274.3): C, 56.9;
H, 5.1; N, 20.4. Found C, 56.8; H, 5.2; N, 20.3%.
N-[5-Acetyl-2-(4-chlorophenyl)-2H-1,2,3-triazol-4-yl]acetamide
(8c): Yellow solid (63%), m.p. 160–162°C. IR: νmax 3287 (NH), 1693
(CO), 1674 cm-1 (CO). NMR (DMSO-d6): δH 2.1 (s, 3H, CH3), 2.6
(s, 3H, CH3), 7.6 (d, 2H, J = 8 Hz, Ar–H), 8.1 (d, 2H, J = 8 Hz, Ar–
H), 10.2 (br, 1H, NH, D2O-exchanged); δC 192 (CO), 169.4 (CO),
145.4, 138.2, 133.9, 130.8 (2CH), 125.3, 121.1 (2CH), 28.7 (CH3),
19.5 (CH3). MS: m/z (%) 278 (M+, 30), 236 (95), 194 (25). Anal.
Calcd for C12H11ClN4O2 (278.7): C, 51.7; H, 3.9; N, 20.1. Found C,
51.6; H, 4.0; N, 19.0%
1-(5-Amino-2-(4-chlorophenyl)-2H-1,2,3-triazol-4-yl)ethanone (3c)
The amidoxime 2c (2.54 g, 0.01 mol) was refluxed for 6–8 h in N,
N-dimethylformamide (10 ml) containing a few drops of piperidine.
The solution was cooled and then poured onto ice-water. The solid
which separated was collected by filtration and crystallised from
petroleum ether (b.p. 60–80°C) to give yellow granules (66%), m.p.
117–118°C. IR: νmax 3479, 3384 (NH2), 1676 cm-1 (CO). NMR
(CDCl3): δH 2.6 (s, 3H, CH3), 5.1 (s, 2H, NH2, D2O-exchanged),
7.4 (d, 2H, J = 8 Hz, Ar–H) 7.9 (d, 2H, J = 8 Hz, Ar–H); δC 194.6
(CO), 154.6, 138.3, 133.9, 130.7 (2CH), 120.7 (2CH), 117.5, 27.2
(CH3). MS: m/z (%) 236 (M+, 100), 194 (15), 125 (10), 111 (65), 90
(20), 75 (10). Anal. Calcd for C10H9ClN4O (236.6): C, 50.8; H, 3.8;
N, 23.6. Found C, 51.2; H, 3.9; N, 23.3%.
4-(4-Methoxyphenyl)-5-methylisoxazol-3-amine (4b)
The nitrile 1b (2.17 g, 0.01 mol), hydroxylamine hydrochloride (0.69
g; 0.01 mol), and sodium acetate (0.82 g, 0.01 mol) were heated
to reflux for 2 h in ethanol (20 ml). After cooling, the mixture was
poured into ice-water. The solid which separated was collected by
filtration and crystallised from petroleum ether (60–80°C) to give
yellow needles (83%), m.p. 165–166°C. IR: νmax 3430, 3274 cm-1
(NH2). NMR (CDCl3): δH 2.7 (s, 3H, CH3), 3.9 (s, 3H, OCH3), 5.3 (s,
1-[2-(4-Chlorophenyl)hydrazono]-1-(5-methyl-1,2,4-oxadiazol-3-
yl)propan-2-one (9c)
Equimolecular amounts of the amidoxime 2c (2.54 g, 0.01 mol) and
acetic anhydride (1.02 g, 0.01 mol) in glacial acetic acid (20 ml) was
PAPER: 07/4783

518 JOURNAL OF CHEMICAL RESEARCH 2007
heated for 2 h under reflux. After cooling, the mixture was poured
into ice-water. The solid so formed was collected by filtration and
crystallised from petroleum ether (b.p. 60–80°C) to give faintly
yellow fibrous crystals (62%), m.p. 170–172°C. IR): νmax 3327 (NH),
1677 cm-1 (CO). NMR: δH (CDCl3) 2.3 (s, 3H, CH3), 2.7 (s, 3H,
CH3), 7.4 (d, 2H, J = 8 Hz, Ar–H), 8.1 (d, 2H, J = 8 Hz, Ar–H),
9.3 (br, 1H, NH, D2O-exchanged); δC (DMSO-d6) 195.5 (CO), 167.8,
147.1, 138.1, 134.8, 130.3 (2CH), 122.2 (2CH), 118.3, 27.6 (CH3),
25.1 (CH3). MS: m/z (%) 278 (M+, 20), 236 (100), 221 (20), 194 (20),
139 (20), 125 (40), 111 (70), 90 (20). Anal. Calcd for C12H11ClN4O2
(278.7): C, 51.7; H, 3.9; N, 20.1. Found C, 51.7; H, 4.0; N, 20.2%.
(2CH), 105.9, 104.5, 19.5 (CH3). MS: m/z (%) 302 (M+, 70), 260 (95),
125 (40), 111 (25), 94 (30), 75 (15). Anal. Calcd for C13H11ClN6O
(302.7): C, 51.5; H, 3.6; N, 27.7. found C, 51.6; H, 3.6; N, 27.7%.
Synthesis of the triazolopyridines 15b,c, general procedure
Benzenediazonium chloride solution was prepared by the standard
literature procedure from aniline (0.93 g, 0.01 mol), concentrated
hydrochloric acid, and sodium nitrite. Compound 10b,c (0.01 mol)
in ethanol (50 ml) was stirred with sodium acetate (5 g), and the
diazonium salt solution was added gradually to the mixture. After
the addition was complete, the reaction mixture was kept at room
temperature for 1 h. The solid which separated was collected by
filtration and crystallised from ethanol to give a dark yellow powder.
2-(4-Methoxyphenyl)-6-(2-phenylhydrazono)-2H-[1,2,3]
triazolo[4,5-b]pyridin-7(6H)-one (15b): Yellow solid (79%), m.p.
253–255°C. IR: νmax 3435 (NH), 1626 cm-1 (CO). NMR: δH (DMSO-
d6) 3.8 (s, 3H, OCH3), 7.1 (d, 2H, J = 8 Hz, Ar–H), 7.4-7.8 (m, 5H,
Ar–H), 8.1 (d, 2H, J = 8 Hz, Ar–H), 8.4 (s, 1H, CH), 15.8 (br, 1H, NH,
D2O-exchanged); δC (CDCl3) 169.3 (CO), 161.0, 159.4, 141.4, 140.2,
135.8, 132.9, 130.4 (2CH), 130.0 (2CH), 130, 129.7, 119.3 (2CH),
115.0 (2CH), 56.6 (CH3). MS: m/z (%) 346 (M+, 100), 269 (15), 241
(75), 158 (25), 107 (25), 72 (25), 77 (70). Anal. Calcd for C18H14N6O2
(346.35): C, 62.4 H, 4.0; N, 24.2. Found C, 62.2; H, 3.9; N, 24.4%.
((Z)-2-(4-Chlorophenyl)-6-(2-phenylhydrazono)-2H-[1,2,3]
triazolo[4,5-b]pyridin-7(6H)-one (15c): yellow solid (70%),
m.p. 192–94°C. IR: νmax 3355 (NH), 1629 cm-1 (CO). NMR: δH
(DMSO-d6) 7.3–7.8 (m, 7H, Ar–H), 8.2 (d, 2H, J = 8 Hz, Ar–H), 8.5
(s, 1H, CH), 16.0 (br, 1H, NH, D2O-exchanged); δC (CDCl3) 169.4
(CO), 161.0, 159.4, 141.4, 140.2, 135.8, 132.9, 130.4 (2CH), 130.2
(2CH), 130, 129.7, 122.3 (2CH), 120.0 (2CH). MS: m/z (%) 350 (M+,
100), 273 (30), 245 (45), 210 (15), 182 (25), 162 (30), 125 (20), 111
(70), 93 (20), 77 (98). Anal. Calcd for C17H11ClN6O (350.7): C, 58.2;
H, 3.1; N, 23.9. Found C, 58.2; H, 3.0; N, 23.7%.
Synthesis of the enaminoketones 10b,c, general procedure
The acetmidotriazole 8b,c (0.01 mol) and N,N-dimethylformamide
dimethylacetal (1.19 g, 0.01 mol) were heated to reflux for 6 h in
xylene (20 ml). The reaction mixture was evaporated under reduced
pressure to yield a crude product which from toluene formed dark
yellow crystals.
N-[5-[3-(Dimethylamino)acryloyl]-2-(4-methoxyphenyl)]-
2H-1,2,3-triazol-4-yl]acetamide (10b): Yellow granules (70%),
m.p. 173–175°C. IR νmax 3254 (NH), 1681 (CO), 1639 cm-1 (CO).
NMR: δH (DMSO-d6) 2.1 (s, 3H, CH3), 2.9 (s, 3H, NCH3), 3.2 (s,
3H, NCH3), 3.8 (s, 3H, OCH3), 5.8 (d, 1H, J = 12 Hz, CH), 7.1 (d,
J = 8 Hz, 2H, Ar–H), 7.8 (d, 1H, J = 12, CH), 7.9 (d, J = 8, 2H,
Ar–H), 10.1 (br, 1H, NH, D2O-exchanged); δC (CDCl3) 186.4 (CO),
167.3 (CO), 155.5, 145.5, 142.0, 134.9, 130.9 (2CH), 128.3, 121.5
(2CH), 92.4, 56.8 (OCH3), 46.0 (NCH3), 38.1 (NCH3), 25.1 (CH3).
MS: m/z (%) 329 (M+, 95), 312 (25), 285 (30), 243 (80), 121 (10), 98
(40), 70 (15). Anal. Calcd for C16H19N5O3 (329.4): C, 58.3; H, 5.8; N,
21.2. Found C, 58.1; H, 5.8; N, 21.3%.
N-[2-(4-Chlorophenyl)-5-(3-(dimethylamino)acryloyl)-2H-1,2,3-
triazol-4-yl]acetamide (10c): Yellow crystals (65%), m.p. 186–
188°C. IR: νmax 3265 (NH), 1686 (CO), 1637 cm-1 (CO). NMR:
δH (DMSO-d6) 2.1 (s, 3H, CH3), 2.9 (s, 3H, NCH3), 3.3 (s, 3H,
NCH3), 5.8 (d, 1H, J = 12 Hz, CH), 7.6 (d, J = 8 Hz, 2H, Ar–H),
7.8 (d, 1H, J = 12 Hz, CH), 8.1 (d, J = 8 Hz, 2H, Ar–H), 10.2 (br,
1H, NH, D2O-exchanged); δC (CDCl3): 180.1 (CO), 167.3 (CO),
155.5, 146.3, 142.0, 138.4, 132.9, 130.5 (2CH), 120.9 (2CH), 91.9,
45.6 (CH3), 38.1 (CH3), 24,5 (CH3). MS: m/z (%) 333 (M+, 80), 316
(40), 292 (90), 263 (40), 247 (80), 221 (40), 111 (20), 98 (95), 70
(20). Anal. Calcd for C15H16ClN5O2 (333.7): C, 53.9; H, 4.8; N, 20.9.
Found C, 53.9; H, 4.8; N, 20.7%.
The authors are grateful to Kuwait University Research
Administration for financial support through project No.
SC11/02 and for SAF facilities projects GS01/01; GS03/01.
Received 9 August 2007 ; accepted 3 September 2007
Paper 07/4783 doi: 10.3184/030823407X244869
References
Synthesis of pyrazolyltriazoles 11b,c, general procedure
1
2
3
S. M. Riyadh, I. A. Abdelhamid, H. M. Ibrahim, H. M. Al-Matar and
M. H. Elnagdi, Heterocycles, 2007, in press.
Equimolecular amounts of 10b,c (0.01 mol) and hydrazine hydrate
(0.5 g, 0.01 mol) in N,N-dimethylformamide (20 ml) were refluxed
for 5 h. After cooling, the reaction mixture was poured into ice-water.
The solid so formed was collected by filtration and crystallised from
ethanol.
2-(4-Methoxyphenyl)-5-(1H-pyrazol-3-yl)-2H-1,2,3-triazol-4-
amine (11b): Yellow granules (70%), m.p. 149–150°C. IR: νmax 3433,
3387 (NH2), 3313 cm-1 (NH). NMR: δH (CDCl3) 3.8 (s, 3H, OCH3),
4.8 (br, 2H, NH2, D2O-exchanged), 6.8 (d, 1H, J = 8 Hz, CH), 6.9 (d,
2H, J = 8 Hz, Ar–H), 7.6 (d, 1H, J = 8 Hz, CH), 7.9 (d, 2H, J = 8 Hz,
Ar–H), 10.3 (br, 1H, NH, D2O-exchanged); δC (DMSO-d6) 158.2,
151.7, 134.2, 130.7, 122.2, 119.2 (2CH), 115.7, 115.6 (2CH), 102.8,
56.4 (CH3). MS: m/z (%) 256 (M+, 100), 241 (30), 121 (20), 107 (20),
92 (20), 77 (20). Anal. Calcd for C12H12N6O (256.3): C, 56.2; H, 4.7;
N, 32.7. Found C, 55.9; H, 4.9; N, 32.5%.
N-[2-(4-Chlorophenyl)-5-(1H-pyrazol-3-yl)-2H-1,2,3-triazol-4-
yl)acetamide (11c): Yellow crystals (68%), m.p. 251–252°C. IR νmax
3258 (NH), 3200 (NH), 1668 cm-1 (CO). NMR: δH (CDCl3) 2.1 (s,
3H, CH3), 6.6 (d, 1H, J = 8 Hz, CH), 7.6 (d, 2H, J = 8 Hz, Ar–H), 7.8
(d, 1H, J = 8 Hz, CH), 8.0 (d, 2H, J = 8 Hz, Ar–H), 10.0 (br, 1H, NH,
D2O-exchanged), 13.2 (br, 1H, NH, D2O-exchanged); δC (DMSO-d6)
170.0 (CO), 142.8, 142.1, 140.8, 138.7, 132.6, 130.7 (2CH), 120.5
F. Al-Omran, M. M. Abdel Khalik, A. A. ElKhair and M. H. Elnagdi,
Synthesis, 1997, 91-94.
V. Kryštof, P. Cankar, I. Fryšová, J. Slouka, G. Kontopidis, P. Dzubák,
M. Hajdúch, J. Srovnal, W.F. de Azevedo, M. Orság, M. Paprskárová,
J. Rolcik, A. Látr, P.M. Fischer, and M. Strnad, J. Med. Chem., 2006,
49, 9500.
4
S. A. Abdallah, N. H. Metwally, H. F. Anwar, and M. H. Elnagdi,
J. Heterocycl. Chem., 2005, 42, 781.
5
6
H.M. Al-Matar, S.M. Riyadh and M.H. Elnagdi, Arkivoc, 2007, xii, 53.
S.I. Aziz, H.F. Anwar, D.H. Fleita and M.H. Elnagdi, J. Heterocycl.
Chem., 2007, 44, 725.
7
8
9
M. H. Elnagdi, M. R. H. Elmoghayer, E. A. Hafez and H. H. Almina,
J. Org. Chem., 1975, 40, 2604.
H. Al-Awadhi, F. Al-Omran, M. H. Elnagdi, L. Infantes, C. Foces-Foces,
N. Jagerovic and J. Elguero, Tetrahedron, 1995, 51, 19.
S.A.S. Ghozlan, I.A. Abdelhamid, H.M. Ibrahim and M.H. Elnagdi,
Arkivoc, 2006, xv, 53.
10 S. M. Al-Mousawi and M. S. Moustafa, Beilstein J. Org. Chem., 2007,
3, 12.
11 A.J. Boulton and A.R. Katritzky, Rev. Chim. (Acad. R.P. Roumaine), 1962,
7, 691.
12 F. Al-Omran, M.M. Abdel Khalik, A.A. ElKhair and M.H. Elnagdi,
Synthesis, 1997, 91.
PAPER: 07/4783