Studies on enamines and azaenamines: 2-Oxoarylhydrazonals as C-1 nucleophiles

Article abstract of DOI:10.3987/COM-08-11373

2-Oxoarylhydrazonals 1a,b react with aldehydes; piperidine; morpholine and benzotriazole to yield the corresponding Mannich bases 2a,f, and 4. Formaldehyde reacts with 1a,b to yield the hydroxymethylarylhyrazons 5a,b together with bisarylhydrazones 6. The hydroxymethyl derivatives 5a are converted to arylhydrazonal 7 upon oxidation in refluxing nitrobenzene. The reaction of aldehydes and malononitrile with 1a,b in ethanolic solution in presence of chitozan as heterogeneous catalyst afforded 6-amino-1,4-dihydropyridazins 14a,b. The Japan Institute of Heterocyclic Chemistry.

Full text of DOI:10.3987/COM-08-11373

HETEROCYCLES, Vol. 75, No. 9, 2008
2201
HETEROCYCLES, Vol. 75, No. 9, 2008, pp. 2201 - 2211. © The Japan Institute of Heterocyclic Chemistry
Received, 25th February, 2008, Accepted, 16th April, 2008, Published online, 21st April, 2008. COM-08-11373
STUDIES ON ENAMINES AND AZAENAMINES: 2-OXOARYLHYDRAZ-
ONALS AS C-1 NUCLEOPHILES
Saleh M. Al-Mousawi,* Moustafa Sherief Moustafa, and Mohamed Hilmy
Elnagdi
Department of chemistry, Faculty of Science; University of Kuwait: Safat; 13060:
Kuwait, p.o. Box 5969, Tel.: +965-4987081; Fax: +965-4816482;
E-mail: salehalmousawi@hotmail.com
Abstract – 2-Oxoarylhydrazonals 1a,b react with aldehydes; piperidine;
morpholine and benzotriazole to yield the corresponding Mannich bases 2a,f, and
4. Formaldehyde reacts with 1a,b to yield the hydroxymethylarylhyrazons 5a,b
together with bisarylhydrazones 6. The hydroxymethyl derivatives 5a are
converted to arylhydrazonal 7 upon oxidation in refluxing nitrobenzene. The
reaction of aldehydes and malononitrile with 1a,b in ethanolic solution in
presence
of
chitozan
as
heterogeneous
catalyst
afforded
6-amino-1,4-dihydropyridazins 14a,b.
INTRODUCTION
Enamines are versatile reagents and their chemistry is receiving considerable recent interest.1-3 Recently
we recognized that aldehyde hydrazones are azaenamines as hydrazone lone pair resonance renders C-1
quite nucleophilic.4-6 In conjunction of this work we report on the reactivity of 2-oxo-1-arylhydrazonals
1a,b toward α,β-unsaturated nitriles and Mannich bases.
RESULTS AND DISCUSSION
Thus 1a or 1b reacted with a mixture of formaldehyde or benzaldehyde and piperidine or morpholine to
yield Mannich bases 2a-f in 60-85 % yields. Benzotriazole reacted also as a secondary amine. Thus
mixing 1a,b with formaldehyde and benzotriazole 3 gave a corresponding Mannich products together
with products of molecular formula C19H20N4O2 (336.39) and C21H24N4O2 (364.45) respectively
corresponding to the condensation of the latter with 1a,b via water elimination together with other
1
product. Although either alkylation at benzotriazole N-1 or N-2 may take place, the H NMR of the
reaction product indicated that only N-1 alkylated products 4 were formed (Scheme 1).

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HETEROCYCLES, Vol. 75, No. 9, 2008
O
R
N
NH
Ph
1
a, R = Me
b, R = Et
1a
N
N
X
NH
R1CHO
HCHO
NH
3
N
X
N
N
O
O
Me
N
R
N
R1
NH
Ph
N
NH
Ph
a, R = Me, R1 = H, X = CH2
b, R = Et, R1 = H, X = CH2
c, R = Me, R1 = H, X = O
d, R = Et, R1 = H, X = O
e, R = Me, R1 = Ph, X = O
f, R = Et, R1 = Ph, X = O
4
2a-f
Scheme 1
The other product in this reaction could also be obtained by treatment of 1a,b with formaldehyde and was
thus assigned structure 6a,b and are assumed to be formed via initial formation of adduct the 5a,b which
then condense with another molecule of 1a,b to yield the final isolable 4. Intermediate 5a,b has been
isolated in 50 and 53 % yields respectively. It is of value to report here that 2a has been obtained earlier
by Mustafa et al. Via reacting 2-phenylhydrazonopenta-2,3,4-trione with Mannich bases.7
Compound 5a could be readily oxidized into arylhydrazonal 7 upon reflux in nitrobenzene. Although the
chemistry of arylhydrazonals have been explored recently by Elnagdi et al.8-11 Utilizing these
arylhydrazonals as precursors to a wide number of heterocycles they utilized expensive functionally
substituted enamines as precursor to those arylhydrazonals. The formation of 5a from 2-oxo-1-
arylhydrazonals may thus provide a quite inexpensive route to arylhydrazonals.
Compound 6b was reacted with dimethylformamide dimethyl acetal (DMFDMA) to afford 8 (Scheme 2).
We have investigated the behavior of 4 toward electrophiles and found that hydrazone carbon is still
nucleophilic in this compound as it coupled with benzenediazonium chloride to yield formazane 10 via
intermediate 9 that readily underwent Japp-Kilingemann reaction to yield 10.12

HETEROCYCLES, Vol. 75, No. 9, 2008
2203
O
O
O
CH2OH
R
R
HCHO
R
1a,b
N
N
N
NH
Ph
HN
NH
Ph
Ph
5a,b
6a,b
nitrobenzene
5a
6b
DMFDMA
CH3
O
O
N
CHO
R
N
N
NH
Ph
Ph
7
8
Scheme 2
It is assumed that hydroxylmethylbenzotriazole 11 is formed in this reaction but could not be isolated.
Reacting 4 with DMFDMA afforded 12 which are formed via initial protonation of 4 to yield 1a that then
condensed with DMFDMA to yield 12 (Scheme 3). Compound 12 could be also obtained, in better yield,
via reacting 1a with DMFDMA.
N
N
O
O
N
N
NPh
N
N
Me
Me
PhN NCl
N
NPh
N
N
+
N
NH
Ph
N
CH2OH
Ph
10
9
11
4
O
DMFDMA
DMFDMA
1a
N
N
Ph
12
Scheme 3

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HETEROCYCLES, Vol. 75, No. 9, 2008
Recently Elnagdi et al.4-6 reported that 1a,b react with benzylidenemalononitrile 13 to yield the
dihydropyridazines 14c,d. We have now found that an equimolar mixture of benzaldehyde and
malononitrile react in refluxing ethanol in the presence piperidine to yield 14a,b in almost same yields
reported earlier for reaction of 1a,b and 13. Attempts to extend this methodology replacing benzaldehyde
by formaldehyde resulted only in the formation of the hydroxymethylarylhydrazone 5. We looked for an
alternate catalyst for this multicomponent reaction. The chitozan has been recently employed efficiently
as a mild basic heterogeneous catalysis. When formaldehyde, malononitrile and 1a were mixed in
ethanolic solution in presence of chitosan, a product of molecular formula C13H12N4O (240.26) was
formed. Although, it seemed quite logical to assign structure 14a for this product, but there is a slim
possibility that this product is really 15 remained. HMBC indicated that, methylene H at δ = 3.17 ppm is
coupled 4J with carbonyl carbon at δ = 196.3 ppm; thus excluding completely possible formation of 15 in
which methylene protons are far from carbonyl carbon. To establish the structure of this product, 14a,c
were hydrolysed by acetic acid in presence of hydrochloric acid to yield a dihydropyridazinone 16a,c (cf.
scheme 4). Moreover, 15NNMR and 15NHMBC were run and inspected 15N spectrum of 14a revealed four
nitrogen signals at δ = 67, 159, 259 and 345 ppm for an amino group, pyridazine N-1, CN group, and
pyridazine N-2 respectively. 1H HMBC-15N indicated an amino protons showing coupled 4J with N at δ =
159 ppm, while 5-CH2 with N at δ = 345 ppm. This further established proposed structure 14a-d.
CN
1a,b
+
R1
CN
13
piperidine / EtOH
R1 = Ph
O
R1
O
R1
CN
R
CN
R
5
chitozan
EtOH
AcOH / HCl
6
4
CH2(CN)2
1a,b
R CHO
1
+
+
N
N 1
3
2
N
14a,c
O
N
NH2
Ph
Ph
16a,c
14a-d
O
NH2
a, R = Me, R1 = H
b, R = Et, R1 = H
CN
R
c, R = Me, R1 = Ph
d, R = Et, R1 = Ph
N
N
R1
Ph
15
Scheme 4

HETEROCYCLES, Vol. 75, No. 9, 2008
2205
CONCLUSION
It could thus be revealed that the title compounds react as C-1 nucleophiles as would be expected for an
azaenamines. A novel route to arylhydrazonals could be achieved. Moreover, the route to the 6-amino-
1,4-dihydropyridazines via multicomponent reaction in presence of chitozan could be further explored.
EXPERIMENTAL
All melting points are uncorrected and were determined with Sanyo (Gallaenkamp) instrument. Infrared
spectra were recorded in KBr and were determined on a Perkin-Elmer 2000 FT–IR system.1H NMR and
1
13C NMR spectra were determined on a Bruker DPX at (100 MHz for H NMR and 125 MHz for 13C
NMR) spectrometer in CDCl3 or DMSO-d6 as solvent and TMS as internal standard; chemical shifts are
reported in δ (ppm). Mass spectra were measured on VG Autospec Q MS 30 and MS 9 (AEI)
spectrometers, with EI 70 EV. Elemental analyses were measured by means of LEOCHNS-932 Elemental
Analyzer.
General procedure to syntheses of compounds (2a-f)
A mixture of 1a,b (0.01 mol) and formaldehyde (0.30 g, 0.01 mol) or benzaldehyde (1.06 g, 0.01 mol) in
presence of piperidine (8 mL) or morpholin (8 mL), were refluxed for 1-2 h (monitored by TLC). The
reaction mixture was evaporated under reduced pressure in vacuum. The solid product, so formed, was
recrystallized from EtOH.
3-(2-Phenylhydrazono)-4-(piperidin-1-yl)butan-2-one (2a)
o
Yellow crystals; yield 85 %; mp 113-115 C. Anal. Calcd for C15H21N3O (259.3): C, 69.47; H, 8.16; N,
1
16.20. Found: C, 69.59; H, 8.16; N, 16.36. IR (cm-1): 2938 (NH), 1661 (CO); H NMR (DMSO-d6): δ,
ppm = 1.40-1.51 (m, 6H, pip-H), 2.20-2.50 (m, 7H, pip-H and Me), 3.56 (s, 2H, CH2), 6.95-7.35 (m, 5H,
Ar-H), 12.11 (br, 1H, NH, D2O exchangeable); 13C NMR (DMSO-d6):δ, ppm = 196.7 (CO), 144.3, 139.5,
130.5 (2C), 122.8, 114.6 (2C), 54.1 (2C), 53.2, 26.7 (2C), 24.9, 24.6. MS: m/z (%) 259 (M+, 45), 167
(100), 123 (65), 98 (95), 77 (80).
2-(2-Phenylhydrazono)-1-(piperidin-1-yl)pentan-3-one (2b)
o
Yellow crystals; yield 82 %; mp 102-103 C. Anal. Calcd for C16H23N3O (273.3): C, 70.30; H, 8.48; N,
1
15.37. Found: C, 70.38; H, 8.67; N, 15.47. IR (cm-1): 2943 (NH), 1664 (CO); H NMR (DMSO-d6): δ,
ppm = 1.02 (t, 3H, J = 8, Me) 1.39-1.51 (m, 6H, pip-H), 2.30 (m, 4H, pip-H), 2.88 (q, 2H, J = 8, CH2),
3.57 (s, 2H, CH2), 6.94-7.35 (m, 5H, Ar-H), 12.08 (br, 1H, NH, D2O exchangeable); 13C NMR
(DMSO-d6): δ, ppm = 199.4 (CO), 144.4, 138.8, 130.5 (2C), 122.7, 114.5 (2C), 54.2 (2C), 53.4, 29.6,
26.7 (2C), 24.6, 9.9. MS: m/z (%) 273 (M+, 25), 187 (60), 122 (50), 104 (85), 77 (100).
4-Morpholino-3-(2-phenylhydrazono)butan-2-one (2c)
o
Yellow crystals; yield 90 %; mp 117-119 C. Anal. Calcd for C14H19N3O2 (261.3): C, 64.35; H, 7.33; N,

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HETEROCYCLES, Vol. 75, No. 9, 2008
16.08. Found: C, 64.39; H, 7.65; N, 15.89. IR (cm-1): 2964 (NH), 1662 (CO); 1H NMR (CDCl3): δ, ppm =
2.49 (m, 7H, morpholin-H, Me), 3.72 (m, 6H, morpholin-H, CH2), 7.02-7.38 (m, 5H, Ar-H), 11.88 (br,
13
1H, NH, D2O exchangeable); C NMR (CDCl3): δ, ppm = 197.5 (CO), 143.8, 138.1, 130.1 (2C), 122.9,
114.4 (2C), 67.7 (2C), 53.4, 53.2 (2C), 24.9. MS: m/z (%) 261 (M+, 15), 169 (55), 105 (50), 100 (60), 77
(100).
1-Morpholino-2-(2-phenylhydrazono)pentan-3-one (2d)
o
Yellow crystals; yield 87 %; mp 108-110 C. Anal. Calcd for C15H21N3O2 (275.3): C, 65.43; H, 7.69; N,
1
15.26. Found: C, 65.62; H, 7.90; N, 15.43. IR (cm-1): 2938 (NH), 1661 (CO); H NMR (DMSO-d6): δ,
ppm = 1.16 (t, 3H, J = 8, Me) 2.48 (m, 4H, morpholin-H), 2.99 (q, 2H, J = 8, CH2), 3.72 (m, 6H,
13
morpholin-H, and CH2), 7.01-7.38 (m, 5H, Ar-H), 11.82 (br, 1H, NH, D2O exchangeable); C NMR
(DMSO-d6): δ, ppm = 200.4 (CO), 143.9, 137.4, 130.1 (2C), 122.8, 114.4 (2C), 67.7 (2C), 53.4, 53.5 (2C),
29.9, 9.6. MS: m/z (%) 275 (M+, 25), 183 (85), 105 (85), 100 (90), 77 (100).
4-Morpholino-4-phenyl-3-(2-phenylhydrazono)butan-2-one (2e)
Yellow crystals; yield 80 %; mp 149-150 oC. Anal. Calcd for C20H23N3O2 (337.42): C, 71.19; H, 6.87; N,
12.45. Found: C, 70.93; H, 7.20; N, 12.66. IR (cm-1): 2974 (NH), 1662 (CO); 1H NMR (CDCl3): δ, ppm =
2.36 (m, 7H, morpholin-H and Me), 3.74 (m, 4H, morpholin-H), 4.93 (s, 1H, CH), 6.99-7.45 (m, 10H,
13
Ar-H), 12.68 (br, 1H, NH, D2O exchangeable); C NMR (CDCl3): δ, ppm = 195.4 (CO), 14.86, 13.78,
136.5, 129.5 (2C), 128.7 (2C), 128.2, 127.7 (2C), 122.2, 113.8 (2C), 67.5, 66.2 (2C), 51.7 (2C), 24.3. MS:
m/z (%) 337 (M+, 85), 250 (100), 207 (20), 176 (20), 105 (20), 77 (10).
1-Morpholino-1-phenyl-2-(2-phenylhydrazono)pentan-3-one (2f)
Yellow crystals; yield 83 %; mp 133-135 oC. Anal. Calcd for C21H25N3O2 (351.45): C, 71.77; H, 7.17; N,
1
11.96. Found: C, 71.64; H, 7.38; N, 11.96. IR (cm-1): 2976 (NH), 1668 (CO); H NMR (DMSO-d6): δ,
ppm = 0.94 (t, 3H, J = 8, Me) 2.50-3.54 (m, 10H, morpholin-H and CH2), 4.93 (s, 1H, CH), 6.99-7.45 (m,
10H, Ar-H), 12.68 (br, 1H, NH, D2O exchangeable); 13C NMR (DMSO-d6): δ, ppm = 198.2 (CO), 142.9,
138.1, 136.6, 129.5 (2C), 129.2 (2C), 128.3, 127.7 (2C), 122.1, 113.7 (2C), 67.7, 66.2 (2C), 51.7 (2C),
28,9, 8.7. MS: m/z (%) 351 (M+, 25), 264 (100), 259 (35), 207 (25), 176 (15), 105 (20), 77 (30).
Synthesis of 4-(1H-benzo[1,2,3]triazol-1-yl)-3-(2-phenylhydrazono)butan-2-one (4)
A mixture of 1a (1.62 g, 0.01 mol), formaldehyde (0.30 g, 0.01 mol) and benzotriazole (1.19 g, 0.01 mol)
in dioxane (10 mL) were refluxed for 1-2 h (monitored by TLC). The reaction mixture was evaporated
under reduced pressure in vacuum yielding a crude product. This crude product contains compounds 4
and 6a. These were separated by long column chromatography using a mixture of petroleum ether ( bp
60-80) and EtOAc (3:1) as an eluent. Compound 4 when separated from column chromatography was
recrystallized from petroleum ether (bp 60-80) and gave yellow crystals; yield 55 %; mp 127-129 oC.
Anal. Calcd for C16H15N5O (293.33): C, 65.52; H, 5.15; N, 23.88. Found: C65.55; H, 5.44; N, 23.59. IR

HETEROCYCLES, Vol. 75, No. 9, 2008
2207
1
(cm-1): 3289 (NH), 1664 (CO); H NMR (CDCl3): δ, ppm = 2.53 (s, 3H, Me), 5.84 (s, 2H, CH2),
13
7.09-8.05 (m, 9H, Ar-H), 10.28 (br, 1H, NH, D2O exchangeable); C NMR (CDCl3): δ, ppm = 196.1
(CO), 145.7, 142.4, 135.1, 132.7, 129.5 (2C), 128.4, 124.7, 123.7, 119.8, 114.8 (2C), 110.4, 38.4, 24.1.
MS: m/z (%) 293 (M+, 90), 222 (65), 195 (50), 174 (30), 118 (70), 105 (90), 91 (60), 77 (100), 65 (50).
General procedure to syntheses of compounds (5a,b) and (6a,b)
A mixture of 1a,b (0.01 mol) and formaldehyde (0.30 g, 0.01 mol), in dioxane (10 mL) were refluxed for
5-7 h (monitored by TLC). The reaction mixture was evaporated under reduced pressure in vacuum
yielding a crude product. This crude product contains two compounded 5a-b and 6a,b. The crude product
was washed with petroleum ether (60-80) to extract the adduct 5a,b as yellow crystals and the remaining
product 6a,b was recrystallized from EtOH giving orange crystals.
4-Hydroxy-3-(2-phenylhydrazono)butan-2-one (5a)
Yellow crystals; yield 50 %; mp 117-119 oC. Anal. Calcd for C10H12N2O2 (192.22): C, 62.49; H, 6.29; N,
1
14.57. Found: C, 62.24; H, 6.52; N, 14.31. IR (cm-1): 3305 (OH), 3280 (NH), 1646 (CO); H NMR
(DMSO-d6): δ, ppm = 2.36 (s, 3H, Me), 4.45 (s, 2H, CH2), 5.25 (br, 1H, OH) D2O exchangeable,
13
6.95-7.36 (m, 5H, Ar-H), 10.51 (br, 1H, NH, D2O exchangeable); C NMR (CDCl3): δ, ppm = 196.1
(CO), 144.0, 142.2, 129.7 (2C), 122.2, 114.5 (2C), 51.6, 24.7. MS: m/z (%) 192 (M+, 90), 174 (30), 162
(10), 105 (95), 92 (85), 77 (100), 65 (75).
1-Hydroxy-2-(2-phenylhydrazono)pentan-3-one (5b)
Yellow crystals; yield 53 %; mp 110-112 oC. Anal. Calcd for C11H14N2O2 (206.24): C, 64.06; H, 6.84; N,
1
13.58. Found: C, 64.20; H, 6.62; N, 13.81. IR (cm-1): 3303 (OH), 3277 (NH), 1652 (CO); H NMR
(DMSO-d6): δ, ppm = 1.38 (t, 3H, J = 8, Me), 3.10 (q, 2H, J = 8, CH2), 4.24 (s, 2H, CH2), 5.58 (br, 1H,
13
OH) D2O exchangeable, 7.01-7.38 (m, 5H, Ar-H), 10.51 (br, 1H, NH, D2O exchangeable); C NMR
(CDCl3): δ, ppm = 198.1 (CO), 146.2, 142.2, 130.7 (2C), 122.3, 115.5 (2C), 51.6, 28,9, 8.7. MS: m/z (%)
206 (M+, 85), 188 (45), 174 (25), 105 (95), 91 (70), 77 (95).
3,5-Bis(2-phenylhydrazono)heptane-2,6-dione (6a)
Orange crystals; yield 40 %; mp 204-205 oC. Anal. Calcd for C19H20N4O2 (336.39): C, 67.84; H, 5.99; N,
16.66. Found: C, 67.88; H, 6.19; N, 16.74. IR (cm-1): 3026 (2NH), 1639 (2CO); 1H NMR (DMSO-d6): δ,
ppm = 2.44 (s, 6H, 2Me), 3.73 (s, 2H, CH2), 7.00-7.40 (m, 10H, Ar-H), 10.96 (br, 2H, 2NH) D2O
exchangeable; 13C NMR (CDCl3): δ, ppm = 196.3 (CO), 143.2, 134.7, 129.3 (2C), 121.6, 113.4 (2C), 24.1,
7.6. MS: m/z (%) 338 (M+2, 15), 337 (M+1, 70), 336 (M+, 85), 319 (15), 229 (30), 202 (45), 108 (100), 93
(15).
4,6-Bis(2-phenylhydrazono)nonane-3,7-dione (6b)
Orange crystals; yield 40 %; mp 137-139 oC. Anal. Calcd for C21H24N4O2 (364.45): C, 69.21; H, 6.64; N,
15.34. Found: C, 68.98; H, 6.89; N, 15.39. IR (cm-1): 3253 (2NH), 1658 (2CO); 1H NMR (DMSO-d6): δ,

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HETEROCYCLES, Vol. 75, No. 9, 2008
ppm = 1.05 (t, 6H, J = 8, 2Me), 2.79 (q, 4H, J = 8, 2CH2), 3.41 (s, 2H, CH2), 6.92-7.33 (m, 10H, Ar-H),
13
11.28 (br, 2H, 2NH) D2O exchangeable; C NMR (CDCl3): δ, ppm = 199.6 (CO), 143.7 134.4, 129.8
(2C), 121.9, 113.8 (2C), 29.6, 8.9, 7.6. MS: m/z (%) 364 (M+, 40), 275 (95), 201 (60), 189 (40), 108 (100),
93 (70), 77 (55), 56 (90).
Synthesis of 3-oxo-2-(2-phenylhydrazono)butanal (7)
A mixture of 5a (1.92 g, 0.01 mol) and nitrobenzene (1 mL) were refluxed for 30 min in an oil bath at 150
oC. After cooling the mixture was poured onto cold petroleum ether (bp 60-80). The solid, so formed, was
collected by filtration and recrystallized from petroleum ether (bp 60-80) to give yellow product; yield
75 %; mp 127-129 ºC. Anal. Calcd for C10H10N2O2 (190.20): C, 63.15; H, 5.30; N, 14.73. Found: C,
63.04; H, 5.52; N, 14.51. IR (cm-1): 3273 (NH), 1746 (CO), 1691 (CHO); 1H NMR (DMSO-d6): δ, ppm =
2.41 (s, 3H, Me), 7.25-7.67 (m, 5H, Ar-H), 9.93 (br, 1H, CHO), 14.14 (br, 1H, NH, D2O exchangeable);
13C NMR (CDCl3): δ, ppm = 196.9 (CO), 187.5 (CHO), 141.8, 132.7, 132.7 (2C), 130.1, 117.3 (2C), 25.1.
MS: m/z (%) 190 (M+, 90), 161 (60), 118 (70), 105 (95), 92 (85), 77 (100).
Synthesis of 5-methyl-1-phenylpyridazin-4(1H)-one (8)
A mixture of compound 6b (3.64 g, 0.01 mol) and N,N-dimethylformamide dimethyl acetal (DMFDMA)
(1.19 g, 0.01 mol) in xylene (10 mL) was refluxed for 6 h. The reaction mixture was evaporated under
reduced pressure in vacuum yielding a crude product, which was crystallized from petroleum ether (bp
60-80) to give colorless product; yield 75 %; mp 130-131oC. Anal. Calcd for C11H10N2O (186.21): C,
1
70.95; H, 5.41; N, 15.04. Found: C, 70.70; H, 5.59; N, 15.37. IR (cm-1): 1628 (CO); H NMR
(DMSO-d6): δ, ppm = 2.16 (s, 3H, Me), 7.28-7.60 (m, 5H, Ar-H), 8.00 (s, 1H, CH), 8.21 (s, 1H, CH); 13C
NMR (125 MHz, CDCl3): δ, ppm = 170.9 (CO), 146.6, 143.5, 138.7, 130.1 (2C), 128.1, 127.5, 121.1 (2C),
13.2. MS: m/z (%) 186 (M+, 100), 158 (15), 130 (95), 104 (15), 77 (55).
Synthesis of 3-acetyl-1,5-diphenylformazan (10)
A solution of compound 4 (2.93 g, 0.01 mol) in EtOH (10 mL) was treated with sodium acetate (2 g).
Benzenediazonium chloride was then added gradually, with stirring, to the mixture. The diazonium salt
being prepared according to the standard literature procedures from aniline (0.93 g, 0.01 mol),
concentrated hydrochloric acid (2.5 mL), and sodium nitrite (0.69 g, 0.01 mol). After complete addition
of the diazonium salt, the reaction mixture was kept at rt for 1 h. The solid, so formed, was collected by
filtration and recrystallized from benzene to give red crystals; yield 87 %; mp 119-121 oC. Anal. Calcd for
C15H14N4O (266.30): C, 67.65; H, 5.30; N, 21.04. Found: C, 67.69; H, 5.62; N, 20.95. IR (cm-1): 3290
1
(NH), 1680 (CO); H NMR (DMSO-d6):δ, ppm = 2.69 (s, 3H, Me), 7.28-7.72 (m, 10H, Ar-H), 15.94 (s,
13
1H, NH) D2O exchangeable; C NMR (CDCl3): δ, ppm = 193.1, 147.4, 141.5, 130.2 (2C), 130.0 (2C),
129.2, 120.1 (2C), 114.8, 26.9. MS: m/z (%) 266 (M+, 85), 222 (15), 195 (25), 161 (35), 119 (30), 105
(70), 92 (100), 77 (90).

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Synthesis of 1-phenylpyridazin-4(1H)-one (12)
A mixture of compound 4 (2.93 g, 0.01 mol) and N,N-dimethylformamide dimethyl acetal (DMFDMA)
(1.19 g, 0.01 mol) in xylene (10 mL) was refluxed for 4-6 h (monitored by TLC). The reaction mixture
was evaporated under reduced pressure in vacuum yielding a crude product, which was crystallized from
o
petroleum ether (bp 60-80) to give colorless product; yield 68 %; mp 90-92 C. Anal. Calcd for
C10H8N2O (172.19): C, 69.76; H, 4.68; N, 16.27. Found: C, 69.76; H, 4.87; N, 16.55; IR (cm-1): 1614
(CO); 1H NMR (DMSO-d6): δ, ppm = 6.64 (d, 1H, CH), 7.28-7.58 (m, 5H, Ar-H), 8.07 (s, 1H, CH), 8.24
13
(d, 1H, CH); C NMR (CDCl3): δ, ppm = 169.8 (CO), 149.3, 142.8, 140.5, 129.6 (2C), 127.7, 120.6
(2C),116.6. MS: m/z (%) 172 (M+, 85), 145 (15), 45 (25), 117 (100), 104 (50), 90 (30), 77 (85), 63 (20).
General procedure to syntheses of compounds (14a-d)
A mixture of 1a,b (0.01 mol), formaldehyde (0.30 g, 0.01 mol) or benzaldehyde (1.06 g, 0.01 mol) and
malononitrile (0.66 g, 0.01 mol) in presence of chitozan (1.5 g) and EtOH (10 mL) as a solvent, were
refluxed for 2-4 h (monitored by TLC using a mixture from petroleum ether (bp 60-80): EtOAc 2:1). The
reaction mixture was evaporated under reduced pressure in vacuum. The solid product, so formed, was
recrystallized from EtOH to give yellow crystals.
6-Acetyl-3-amino-2-phenyl-2,5-dihydropyridazine-4-carbonitrile (14a)
Yield 70 %; mp 154-155 oC. Anal. Calcd for C13H12N4O (240.26): C, 64.99; H, 5.03; N, 23.32. Found: C,
1
64.75; H, 5.30; N, 23.00; IR (cm-1): 3358, 3314 (NH2), 2186 (CN), 1678(CO); H NMR (DMSO-d6): δ,
ppm = 2.41 (s, 3H, Me), 3.17 (s, 2H, CH2), 5.68 (br, 2H, NH2) D2O exchangeable, 7.28-7.54 (m, 5H,
13
Ar-H); C NMR (CDCl3): δ, ppm = 196.6 (CO), 150.3, 143.7, 139.7, 129.7 (2C), 128.4, 125.7 (2C),
120.3, 52.7, 24.5, 20.2. MS: m/z (%) 240 (M+, 70), 197 (100), 180 (30), 170 (75), 119 (50), 77 (85), 65
(15).
3-Amino-2-phenyl-6-propionyl-2,5-dihydropyridazine-4-carbonitrile (14b)
Yield 75 %; mp 125-126 oC. Anal. Calcd for C14H14N4O (254.29): C, 66.13; H, 5.55; N, 22.03. Found: C,
66.28; H, 5.83; N, 21.70; IR (cm-1): 3400, 3327 (NH2), 2181 (CN), 1682 (CO); 1H NMR (DMSO-d6): δ,
ppm = 1.14 (t, 3H, J = 8, Me), 2.86 (q, 2H, J = 8, CH2), 3.27 (s, 2H, CH2), 4.27 (br, 2H, NH2) D2O
13
exchangeable, 7.41-7.54 (m, 5H, Ar-H); C NMR (CDCl3): δ, ppm = 199.3 (CO), 150.3, 143.3, 139.8,
129.7 (2C), 128.3, 125.6 (2C), 120.3, 52.7, 29.9, 20.4, 8.2. MS: m/z (%) 254 (M+, 80), 197 (100), 170
(30), 119 (25), 77 (35).
6-Acetyl-3-amino-2,5-diphenyl-2,5-dihydropyridazine-4-carbonitrile (14c)
Yield 85 %; mp 236-238 ºC. Anal. Calcd for C19H16N4O (316.36): C, 72.14; H, 5.10; N, 17.7. Found: C,
71.80; H, 5.44; N, 17.42; IR (cm-1): 3411, 3311 (NH2), 2192 (CN), 1677 (CO); 1H NMR (DMSO-d6): δ,
ppm = 2.33 (s, 3H, Me), 3.33 (s, 1H, CH), 6.05 (br, 2H, NH2) D2O exchangeable, 7.18-7.56 (m, 10H,
13
Ar-H); C NMR (CDCl3): δ, ppm = 196.3 (CO), 150.7, 144.4, 142.5, 140.6, 129.8 (2C), 129.5 (2C),

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HETEROCYCLES, Vol. 75, No. 9, 2008
128.3, 127.7, 127.3 (2C), 126.2 (2C), 121.1, 57.2, 36.5, 25.2. MS: m/z (%) 316 (M+, 15), 273 (90), 246
(30), 239 (100), 197 (15), 180 (10), 119 (25), 77 (45), 65 (15).
3-Amino-2,5-diphenyl-6-propionyl-2,5-dihydropyridazine-4-carbonitrile (14d)
Yield 88 %; mp 250-252 oC. Anal. Calcd for C20H18N4O (330.39): C, 72.71; H, 5.49; N, 16.96. Found: C,
72.59; H, 5.70; N, 16.68; IR (cm-1): 3464, 3316 (NH2), 2186 (CN), 1688 (CO); 1H NMR (DMSO-d6): δ,
ppm = 1.04 (t, 3H, J = 8, Me), 2.94 (q, 2H, J = 8, CH2), 4.76 (s, 1H, CH), 6.06 (br, 2H, NH2) D2O
exchangeable, 7.18-7.55 (m, 10H, Ar-H); 13C NMR (CDCl3): δ, ppm = 198.4 (CO), 150.3, 143.3, 142.1,
140.1, 129.5 (2C), 128.9 (2C), 127.8, 127.2, 126.7 (2C), 125.6 (2C), 120.4, 56.8, 36.2, 29.5, 7.9. MS: m/z
(%) 330 (M+, 50), 273 (100), 253 (95), 246 (60), 197 (25), 170 (15), 156 (15), 118 (25), 93 (15), 77 (75),
56 (75).
General procedure to the syntheses of compounds (16a,c)
A mixture of 14a,c (0.01 mol), acetic acid (10 mL) and 37% hydrochloric acid (3.5 mL), were refluxed
for 15 min. The mixture was cooled and then poured onto ice-water. The solid, so formed, was collected
by filtration and crystallized from petroleum ether (bp 60-80) to give yellow crystals.
6-Acetyl-3-oxo-2-phenyl-2,3,4,5-tetrahydropyridazine-4-carbonitrile (16a)
Yield 80 %; mp 145-157 oC. Anal. Calcd for C13H11N3O2 (241.25): C, 64.72; H, 4.60; N, 17.42. Found: C,
1
64.73; H, 4.86; N, 17.10; IR (cm-1): 2261 (CN), 1708 (CO), 1692 (CO); H NMR (DMSO-d6): δ, ppm =
13
2.51 (s, 3H, Me), 3.16-3.90 (m, 3H, CH, CH2), 7.38-7.64 (m, 5H, Ar-H); C NMR (CDCl3): δ, ppm =
195.1, 157.5, 147.5, 139.6, 129.3 (2C), 128.2, 124.7 (2C), 112.6, 31.3, 24.5, 23.6. MS: m/z (%) 241 (M+,
100), 239 (50), 216 (20), 198 (35), 170 (20), 145 (15), 120 (25), 91 (30), 77 (85).
6-Acetyl-3-oxo-2,5-diphenyl-2,3,4,5-tetrahydropyridazine-4-carbonitrile (16c)
Yield 75 %; mp 165-166 oC. Anal. Calcd for C19H15N3O2 (317.35): C, 71.91; H, 4.76; N, 13.24. Found: C,
1
72.04; H, 5.11; N, 13.46; IR (cm-1): 2262 (CN), 1699 (CO), 1690 (CO); H NMR (DMSO-d6): δ, ppm =
2.48 (s, 3H, Me), 4.29 (d, 1H, J = 8, CH), 4.94 (d, 1H, J = 8, CH), 7.25-7.59 (m, 10H, Ar-H); 13C NMR
(CDCl3): δ, ppm = 194.6, 157.5, 157.4, 149.4, 139.5, 131.7, 129.9 (2C), 129.2 (2C), 128.4, 127.8 (2C),
124.4 (2C), 112.9, 39.4, 39.1, 24.8. MS: m/z (%) 317 (M+, 100), 290 (20), 246 (20), 220 (15), 180 (10),
156 (35), 129 (15), 116 (25), 91 (15), 77 (35).
ACKNOWLEDGEMENTS
The authors are grateful to Kuwait University Research Administration for the financial support of project
SC10/06 and for SAF facilities project GS01/02 and GS03/01.
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