Scope and limitations of a novel synthesis of 3-arylazonicotinates

Article abstract of DOI:10.3390/molecules17055924

The reaction of 3-oxo-3-phenyl-2-phenylhydrazonal with functionally substituted and heteroaromatic substituted acetonitrile to yield arylazonicotinic acid derivatives and 5-arylsubstituted pyridines was established. In some cases the produced nicotinates could not be isolated as they underwent thermally induced 6p-electrocyclization yielding polynuclear pyridine derivatives.

Full text of DOI:10.3390/molecules17055924

Molecules 2012, 17, 5924-5934; doi:10.3390/molecules17055924
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Scope and Limitations of a Novel Synthesis of
3-Arylazonicotinates
Omniya Sayed Zaky 1,*, Moustafa Sherief Moustafa 2,*, Maghraby Ali Selim 1,
Awatef Mohamed El-Maghraby 1 and Mohamed Hilmy Elnagdi 2
1
Chemistry Department, Faculty of Science at Qena, South Valley University, P.O. Box 83523,
Qena, Egypt
2
Department of Chemistry, Faculty of Science, University of Kuwait, P.O. Box 5969,
Safat 13060, Kuwait
* Authors to whom correspondence should be addressed; E-Mails: chem_omniya@yahoo.com (O.S.Z.);
mostafa_msm@hotmail.com (M.S.M.).
Received: 27 January 2012; in revised form: 13 May 2012 / Accepted: 15 May 2012 /
Published: 18 May 2012
Abstract: The reaction of 3-oxo-3-phenyl-2-phenylhydrazonal with functionally substituted
and heteroaromatic substituted acetonitrile to yield arylazonicotinic acid derivatives and
5-arylsubstituted pyridines was established. In some cases the produced nicotinates could
not be isolated as they underwent thermally induced 6π-electrocyclization yielding
polynuclear pyridine derivatives.
Keywords: 3-oxo-3-phenyl-2-phenylhydrazonal; arylazonicotinic acid; pyridine;
electrocyclization; heteroaromatics
1. Introduction
3-oxo-3-Substituted-2-arylhydrazonals 1 are versatile, readily obtainable reagents [1] that have been
extensively utilized in the synthesis of polyfunctional substituted aromatics and heteroaromatics [2,3].
In the past we have reported novel synthesis of polyfunctional pyridazines 4 via heating 1 with
dimethyl acetylenedicarboxylate (2) as well as acrylonitrile (3) in presence of triphenylphosphine or a
tertiary amine base [4,5] (Scheme 1). We have also reported that condensing active methylene nitriles
5 with 1 affords products that were believed to be the pyridazine imines 6 [6]. Recently however
Al-Mousawi et al. [7,8] realized that this structure cannot be correct as reported 13C-NMR data for the

Molecules 2012, 17
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product lacked a carbonyl carbon at δ < 175 ppm. It was revealed that the products of condensing 1
with ethyl cyanoacetate are really the arylazonicotinates 7 (cf. Scheme 1), as clearly revealed by the
X-ray crystal structure (Figure 1).
Scheme 1. Chemical reactivies of 3-oxo-3-substituted-2-arylhydrazonals 1.
O
O
CO2Me
O
CN
CN
CO2Me
CO2Me
CHO
R
R
CO2Me
2
R
3
N
N
N
N
N
NH
Ar
Ar
10
1
Ar
4
CN
H2C
X=CO2Et
X
5
O
O
O
X
X
R
R
X
HN
N
N
N
NH
N
O
R
Ar
Ar
N
6
N
8
7
Ph
O
X
N
N
N
Ar
9
Figure 1. X-ray structure of compound 7.

Molecules 2012, 17
5926
However, in some case pyridazinones 8 were the reaction products rather than nicotinates. In light of
the enormous potential of arylazonicotinates both as new pyridone dyes [9] and as biologically active
compounds with anticonvulsant activity that act due to synaptic and non-synaptic mechanisms and some
studies that have proved their antitumor and antimicrobial activities [10], we were interested in defininh
further the behavior of 1 toward 5 to see if the reaction would afford 7 or 8. In the present article we
report on the reactivity of 1a–d toward a variety of derivatives of 5 where we noted that this reaction
may produce derivatives of 7 or 8 depending on the nature of 5. Distinguishing between 7 and 8 could be
easily accomplished based on 13C-NMR data as the absence of a carbonyl carbon signal would mean that
the product is not an arylpyridazine derivative. Also with some derivatives of 7 electrocyclization and
loss of hydrogen leading to novel 6-aryl-6H-pyrido[3,2-c]cinnolin-2-ones 9 seems probable.
2. Results and Discussion
Compounds 1a–d reacted with malononitrile 5b yielding the arylazonicotinonitriles 7b,h,
respectively as indicated by the absence of carbonyl carbon absorptions in the 13C-NMR of the
products. Similar to their behavior toward malononitrile compounds, 1a–d condensed with 5a,c–k to
yield phenylazonicotinates 7a,c–g (Scheme 2).
Scheme 2. Syntheses of phenylazonicotinates 7a,c–g.
O
O
C N
C H O
R
C N
R
E tO H
pip
H 2
C
N
X
+
N
X
N H
P h
N H
P h
5
A
1
a, X = C O 2E t
b , X = C N
a, R = P h
N H
b , R = p-P hC 6H 4
c, R = 2-thionyl
d , R = 2-fiuryl
c, X = C O N H 2
d , X = C S N H 2
e, X = C O N H N H 2
X
O
N
f, X =
S
O
R
N
N
g, X =
N
H
N P h
O
N
N
h , X =
X
B
S
H N
j, X =
N
H
R
P h
N
S
N
k , X =
P h
7
N
L , X = C O N H N = C H P h
a, R = P h;
b , R = P h;
c, R = P h;
d , R = P h;
e, R = p-P hC 6H 4 ;
f, R = p-P hC 6 H 4 ;
X =
X = C N
S
O
X = C O N H 2
X = C S N H 2
X = C N
X = C O N H N H 2
N
g, R = 2-thionyl;
h , R = 2-furyl;
X =
S
X = C N
Phenylazonicotinates 7a,b were converted to aminopyridinones 10a,b by reduction using Zn/AcOH
(Scheme 3).

Molecules 2012, 17
5927
Scheme 3. Syntheses of aminopyridinones 10a,b.
O
O
X
X
HN
AcOH
HN
Zn
Ph
Ph
N
NH2
NPh
10a,b
7a,b
The reaction of 1a,b with 5c,d,k in ethanolic piperidine solution resulted in the formation of 12a–c.
It is believed that the initially formed derivative of 7 readily underwent a 6π electrocyclization yielding
11a–c that then aromatized to the final products 12a–c (Scheme 4).
Scheme 4. Syntheses of compounds 12a–c.
O
O
X
HN
CHO
EtOH
pip
5c,d,k
+
N
R
NH
Ph
N
R
N
Ph
1a,b
7a-c
electrocyclization
O
N
O
X
X
Aromatized
N
HN
N
NH
R
N
R
Ph
Ph
Ph
11a-c
12
a, R= H,
S
N
X=
b, R= Ph, X= CONH2
c, R= Ph, X= CSNH2
We believe that the decreased aromaticity of the thiophene ring as compared to benzene is behind
this ready electrocyclization, and in support of this conclusion we have found that 1c also afforded
14b–d,g,k upon reaction with 5b–d,g,k; again the initially formed derivative of 7 underwent
electro-cyclization to 13 and then aromatized to yield 14b–d,g,k (Scheme 5).

Molecules 2012, 17
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Scheme 5. Syntheses of compounds 14b–d,g,k.
O
N
X
O
HN
CHO
EtOH
pip
S
5b-d,g,k
+
S
N
NH
Ph
N
Ph
1c
7b-d,g,k
O
X
N
O
X
S
Aromatized
HN
N
S
N
Ph
NH
N
14b-d,g,k
Ph
13b-d,g,k
Similar to this behavior compound 1d reacted with 5c–e,g–k to afford compounds 16c–e,g–k under
the same reaction conditions (Scheme 6).
Scheme 6. Syntheses of compounds 16c–e,g–k.
O
X
O
HN
CHO
O
EtOH
pip
5b-d,g-k
+
O
N
NH
N
NH
Ph
Ph
1d
15c-e,g-k
O
X
N
Aromatized
O
N
N
Ph
16c-d,g-k-L

Molecules 2012, 17
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In summary, we could clearly demonstrate that the structures of the products obtained by reacting
1a–d with active methylenes can be readily concluded via inspection of position of the carbonyl
carbon signals in the corresponding 13C-NMR spectra. When a arylhydrazone moiety in the
intermediates cyclises via addition to a CN function subsequent hydrolysis of the formed imine usually
occured leading to pyridazinones.
3. Experimental Section
3.1. General
Melting points are reported uncorrected and were determined with a Sanyo (Gallaenkamp)
instrument. Infrared spectra were recorded using KBr pellets and a Perkin-Elmer 2000 FT-IR
1
13
instrument. H- and C-NMR spectra were determined using a Bruker DPX instrument at 400 MHz
1
for H-NMR and 100 MHz for 13C-NMR and DMSO-d6 solutions with TMS as internal standard.
Chemical shifts are reported in δ (ppm). Mass spectra were measured using a VG Autospec Q MS 30
and MS 9 (AEI) spectrometers, using the EI (70 EV) mode. Elemental analyses were carried out using
a LEO CHNS-932 Elemental Analyzer
3.2. General Procedure for the Synthesis of Compounds 7a,c–g
A mixture of 1a–d (0.01 mmol), and active methylenenitrile derivatives 5a–l (0.01 mmol) in the
presence of piperidine (5 drops) and ethanol (10 mL) as a solvent was refluxed for 1–2 h. The reaction
mixture was evaporated. The solid product, so formed, was crystallized from a suitable solvent.
3-(4-Oxo-4,5-dihydrothiazol-2-yl)-6-phenyl-5-phenylazo-1H-pyridin-2-one (7a). Red crystals from
ethanol, yield 95%; m.p. up 300 °С; Anal. Calcd. for C20H14N4O2S (374) calcd: C, 64.16; H, 3.77;
1
N, 14.96. Found: C, 64.00; H, 3.54; N, 14.83; IR (KBr) υmax: 1,629 (CN), 1,670 (CO); H-NMR
(DMSO-d6): δ = 1.3 (s, 2H, CH2); 7.0–8.1 (m, 10H, Ph-H); 10.0 (br, 1H, NH, D2O exchangeable);
13C-NMR (DMSO-d6): δ = 163.7, 162.9, 143.0, 137.0, 134.9, 129.0, 128.4, 127.7, 126.2, 124, 100.0,
39.0; MS: m/z (%) 373 (M+, 10), 299 (85), 224 (5), 140 (20).
2-Oxo-6-phenyl-5-phenylazo-1,2-dihydropyridine-3-carbonitrile (7b). Dark yellow crystals from
ethanol, yield 95%; m.p. 153 °С; Anal. Calcd. for C18H12N4O (300): C, 71.99; H, 4.03; N, 18.66.
13
Found: C, 71.80; H, 3.99; N, 18.53; IR (KBr): υmax: 3,264 (NH), 1,660 (CO); C-NMR (DMSO-d6):
δ = 162.9, 156.9, 137, 134.9, 129.0, 128.4, 127.7, 126.2, 117.2, 106.7, 100.0; MS: m/z (%) 301 (M+,
50), 275 (20), 194 (15).
2-Oxo-6-phenyl-5-phenylazo-1,2-dihydropyridine-3-carboxylic acid amide (7d). Orange crystals from
ethanol, yield 98%, m.p. 190 °С; Anal. Calcd. for C18H14N4OS (334): C, 64.65; H, 4.22; N, 16.75.
Found: C, 64.59; H, 4.21; N, 16.62; IR (KBr): υmax: 3,399–3,266 (NH2), 1,614(CN), 1,680 (CO);
13
1H-NMR (DMSO-d6):  = 7.4–7.9 (m, 10H, Ph-H); 10.6 (br, 2H, NH2, D2O exchangeable); C-NMR
(DMSO-d6):  = 164.7, 135.7, 133.0, 130.3, 128.1, 126.4; MS: m/z (%) 334 (M+, 100), 105 (30),
77 (25).

Molecules 2012, 17
5930
6-Biphenyl-4-yl-2-oxo-5-phenylazo-1,2-dihydropyridine-3-carbonitrile (7e). Green crystals from
AcOH, yield 95%; m.p. 145 °С; Anal. Calcd. for C24H16N4O (376.13): C, 76.58; H, 4.28; N, 14.88.
13
Found: C, 76.57; H, 4.21; N, 14.62; IR (KBr) υmax: 3,343 (NH), 2,202 (CN), 1,655 (CO); C-NMR
(DMSO-d6): δ = 162.0, 156.9, 137.0, 136.6, 135.8, 132.8, 129.0, 127.4, 126.7, 117.2, 106.7, 100.0;
MS: m/z (%) 377 (M+, 90), 244 (20), 152 (50), 77 (30).
6-Biphenyl-4-yl-2-oxo-5-phenylazo-1,2-dihydropyridine-3-carboxylic acid hydrazide (7f). Buff
crystals from ethanol, yield 95%; m.p. 237 °С; Anal. Calcd. For C24H19N5O2 (409): C, 70.40; H, 4.68;
N, 17.10. found: C, 70.39; H, 4.61; N, 17.02; IR (KBr): υmax: 3,412–3,331 (NH2), 1,660 (CO);
13C-NMR (DMSO-d6): δ = 165.9, 162.9, 148.5, 137.0, 136.6, 135.8, 133.8, 131.3, 129.0, 127.4, 126.7,
100.0; MS: m/z (%) 409 (M+, 50) 324 (80), 181 (75), 77 (70).
3-Benzothiazol-2-yl-5-phenylazo-6-thiophen-2-yl-1H-pyridin-2-one (7g). Yellow crystals from
ethanol/AcOH, yield 98%; m.p. 242 °С; Anal. Calcd. for C22H14N4OS2 (414): C, 63.75; H, 3.40;
1
N, 13.52. Found: C, 63.71; H, 3.31; N, 13.42; IR (KBr): υmax: 3,264 (NH), 1,680 (CO); H-NMR
(DMSO-d6): δ = 7.2–7.3 (t, 3H, thiol-H); 7.6–8.2 (m, 9H, Ph-H); 8.6 (br, 1H, NH, D2O exchangeable);
9.0 (s, 1H, nicotine-H);13C-NMR (DMSO-d6): δ = 162.9, 156.0, 153.0, 137.7, 136.6, 133.0, 130.0,
129.0, 127.8, 126.4, 125.0, 124.0, 123.0, 122.0, 106; MS: m/z (%) 413(M+, 100), 304 (25), 111 (40),
77 (10).
6-Furan-2-yl-2-oxo-5-phenylazo-1,2-dihydropyridine-3-carbonitrile (7h). Green crystals from ethanol,
yield 95%; m.p. 214 °С; Anal. Calcd. for C16H10N4O2 (290): C, 66.20; H, 3.47; N, 19.30. Found:
1
C, 66.19; H, 3.31; N, 19.30; IR(KBr): υmax: 3,322 (NH), 1,631 (CO); H-NMR (DMSO-d6):
δ = 6.7–7.4 (m, 3H, furan-H); 7.6 (m, 2H, Ph-H); 8.1 (m, 2H, Ph-H); 8.1 (m, 1H, Ph-H); 13C-NMR
(DMSO-d6): δ = 149.1, 148.7, 133.3, 130.4, 129.9, 126.1, 123.3, 112.8, 79.1; MS: m/z (%) 289 (M+,
100), 197 (5), 130 (5), 77 (50).
Synthesis of 5-Amino-3-(4-oxo-thiazolidin-2-yl)-6-phenyl-1H-pyridin-2-one (10a). A mixture of 7a
(3.6 g, 0.1 mol) and Zn powder (2 gm) in acetic acid (20 mL) was refluxed for 2 h. then filtered while
hot. The reaction mixture was cooled to room temperature and then poured onto ice-water. The solid
thus formed was collected by filtration and crystallized from AcOH to give black crystals, yield 70%;
m.p. up 300 °С; Anal. Calcd. for C14H13N3O2S (287): C, 58.52; H, 4.56; N, 14.62. Found: C, 58.50;
H, 4.54; N, 14.53; IR (KBr): υmax: 3,432, 3,213 (NH2), 1,658 (CO); 13C-NMR (DMSO-d6): δ = 164.0,
162.9, 134.9, 128.4, 127.7, 126.2, 121.0, 108.0, 51.4, 39.0; MS: m/z (%) 287 (M+, 50), 207 (10), 93 (65),
55 (40).
Synthesis of 5-Amino-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (10b). A mixture of 7b
(0.1 mol) and and Zn powder (2 gm) in acetic acid (20 mL) was refluxed for 2 h. then filtered while
hot. The reaction mixture was cooled to room temperature and then poured onto ice-water. The solid
thus formed was collected by filtration and crystallized from AcOH to give pale brown crystals, yield
70%; m.p. 190 °С; Anal. Calcd. for C12H9N3O (211): C, 68.24; H, 4.29; N, 19.89. Found: C, 68.20;
H, 4.19; N, 19.83; IR (KBr): υmax: 3,432, 3,312, (NH2), 1,640 (CO); 13C-NMR (DMSO-d6): δ = 162.0,

Molecules 2012, 17
5931
156.9, 134.9, 128.4, 127.7, 126.0, 121.1, 117.2, 108.0, 106.7; MS: m/z (%) 211 (M+, 10), 129 (25),
77 (80).
6-Phenyl-3-(4-phenylthiazol-2-yl)-6H-pyrido[3,2-c]cinnolin-2-one (12a). Deep red crystals from
ethanol, Yield 98%; m.p. 150 °С; Anal. Calcd. for C26H16N4OS (432): C, 72.20; H, 3.73; N, 12.95.
1
Found: C, 72.19; H, 3.61; N, 12.92; IR (KBr): υmax: 1,614 (CN), 1,680 (CO); H-NMR (DMSO-d6):
δ = 7.2 (s, 1H, thiazole-H); 7.3–8.1 (m, 14H, Ph-H); 8.3 (s, 1H, nicotine-H); 13C-NMR (DMSO-d6):
δ = 157.2, 154.9, 149.2, 141.1, 140.6, 136.1, 134.3, 133.3, 133.2, 131.1, 130.8, 130.7, 130.1, 129.3,
128.8, 128.5, 127.0, 126.6, 121.3, 120.9; MS: m/z (%) 433 (M+, 100), 329 (10), 105 (20), 77 (15).
2-Oxo-6,8-diphenyl-2,6-dihydropyrido[3,2-c]cinnoline-3-carboxylic acid amide (12b). Red crystals
from ethanol, yield 90%; m.p. 230 °С; Anal. Calcd. for C24H16N4O2 (392): C, 73.46; H, 4.11; N, 14.28.
Found: C, 73.35; H, 4.00; N, 14.11; IR (KBr): υmax: 3,267, 3,189 (NH2); 13C-NMR (DMSO-d6):
δ = 165.0, 150.0, 148.9, 144.2, 139.8, 136.6, 130.0, 129.4, 127.4, 119.5, 118.0, 117.0; MS: m/z (%)
393 (M+, 100), 181 (75), 77 (50).
2-Oxo-6,8-diphenyl-2,6-dihydropyrido[3,2-c]cinnoline-3-carbothioic acid amide (12c). Orange
crystals from AcOH, yield 95%; m.p. 170 °С; Anal. Calcd. for C24H16N4OS (408): C, 70.57; H, 3.95;
N, 13.72. Found: C, 70.49; H, 3.71; N, 13.52; IR (KBr): υmax 3,399, 3,298 (NH2), 1670 (CO);
13C-NMR (DMSO-d6): δ = 164.0, 155.0, 144.0, 143.2, 141.0, 139.8, 136.6, 130.6, 129.0, 127.0, 119.5,
118.0, 116.9; MS: m/z (%) 407 (M+, 25), 391 (50), 151 (40), 51 (50).
8-Oxo-4-phenyl-4,8-dihydro-1-thia-4,5,9-triazacyclopenta[a]naphthalene-7-carbonitrile (14b). Yellow
crystals from ethanol, yield 97%; m.p. 210 °С; Anal. Calcd. for C16H8N4OS (304): C, 63.15; H, 2.65;
1
N, 18.14. Found: C, 63.05; H, 2.52; N, 18.11. IR (KBr): υmax: 1,640 (CO); H-NMR (DMSO-d6):
δ = 7.2–7.5 (m, 2H, thiazole-H); 7.6–7.7 (m, 5H, Ph-H); 13C-NMR (DMSO-d6): δ = 141.4, 138.7,
138.4, 136.8, 136.9, 135.8, 134.9, 132.7, 131.7, 129.7, 129.0, 128.2, 127.8, 126.1, 117.2, 79.16; MS:
m/z (%) 305 (M+, 80), 195 (5), 83 (15), 77 (25).
8-Oxo-4-phenyl-4,8-dihydro-1-thia-4,5,9-triazacyclopenta[a]naphthalene-7-carboxylic acid amide (14c).
Orange crystals from ethanol, yield 98%; m.p. 270 °С; Anal. Calcd. for C16H10N4O2S (322): C, 59.62;
H, 3.13; N, 17.83. Found: C, 59.59; H, 3.11; N, 17.80. IR (KBr): υmax: 3,400, 3,312 (NH2), 1,615 (CN),
1
1,680 (CO); H-NMR (DMSO-d6): δ = 7.2–7.2 (t, 2H, thiol-H); 7.6–8.0 (m, 5H, Ph-H); 8.1 (S, 1H,
13
nicotine-H); C-NMR (DMSO-d6): δ = 147.5, 139.3, 139.0, 138.1, 137.2, 136.2, 133.3, 133.0, 130.3,
129.9, 128.8, 128.2, 126.1, 115.0, 114.2; MS: m/z (%) 323 (M+, 100), 306 (15), 111 (90), 77 (30).
8-Oxo-4-phenyl-4,8-dihydro-1-thia-4,5,9-triazacyclopenta[a]naphthalene-7-carbothioic acid amide (14d).
Brown crystal from ethanol/AcOH, yield 90%; m.p. 195 °С; Anal. Calcd. for C16H10N4OS2 (338):
C, 56.79; H, 2.98; N, 16.56. Found: C, 56.65; H, 2.82; N, 16.41; IR (KBr): υmax: 1,640 (CO), 1,620
13
(CN); C-NMR (DMSO-d6): δ = 164.15, 146.7, 144.0, 141.0, 129.3, 127.0, 126.0, 118.5, 115.1; MS:
m/z (%) 339 (M+, 25), 111 (75), 77 (50).
7-(1H-Benzoimidazol-2-yl)-4-phenyl-4H-1-thia-4,5,9-triazacyclopenta[a]naphthalen-8-one (14g). Yellow
crystals from ethanol, yield 95%; m.p. 230 °С; Anal. Calcd. for C22H13N5OS (395): C, 66.82; H, 3.31;

Molecules 2012, 17
5932
1
N, 17.71. Found: C, 66.70; H, 3.21; N, 17.68; IR (KBr): υmax: 1,670 (CO), 1,620 (CN); H-NMR
(DMSO-d6): δ = 7.2–7.2 (t, 1H, NH, D2O exchangeable); 7.2–7.3 (m, 2H, thiol-H); 7.5–8.1 (m, 9H,
13
Ph-H); 8.4 (s, 1H, nicotine-H); C-NMR (DMSO-d6): δ = 151.9, 147.0, 138.5, 136.9, 136.0, 129.1,
128.9, 128.4, 128.1, 126.5, 123.3, 121.0; MS: m/z (%) 396 (M+, 100), 286 (25), 195 (15), 111 (90),
77 (30).
4-Phenyl-7-(4-phenylthiazol-2-yl)-4H-1-thia-4,5,9-triazacyclopenta[a]naphthalen-8-one (14K). Yellow
crystals from ethanol, yield 95%; m.p. 200 °С; Anal. Calcd. for C24H14N4OS2 (438): C, 65.73; H, 3.22;
1
N, 12.78. Found: C, 65.70; H, 3.11; N, 12.68; IR (KBr): υmax: 1,680 (CO), 1,620 (CN); H-NMR
(DMSO-d6): δ = 7.2–7.4 (t, 2H, thiol-H); 7.4–8.1 (m, 10H, Ph-H); 8.41 (s, 1H, thiazole-H); 8.6 (s, 1H,
13
nicotine-H); C-NMR (DMSO-d6): δ = 154.4, 140.2, 138.5, 137.0, 136.2, 133.8, 130.7, 130.3, 129.7,
128.9, 128.3, 128.1, 126.6, 126.1, 121.0, 119.52; MS: m/z (%) 439 (M+, 100), 368 (5), 236 (10), 111 (20).
8-Oxo-4-phenyl-4,8-dihydro-1-oxa-4,5,9-triazacyclopenta[a]naphthalene-7-carboxylic acid amide (16c).
Yellow crystals from ethanol, yield 95%; m.p. 288 °С; Anal. Calcd. for C16H10N4O3 (306): C, 62.74;
H, 3.29; N, 18.29.;Found: C, 56.40; H, 3.44; N, 16.32; IR (KBr): υmax: 1,685 (CO), 1,620 (CN);
1H-NMR (DMSO-d6): δ = 6.7–6.7 (m, 2H, furan-H); 7.0 (s, 1H, nicotine-H); 7.5–8.4 (m, 5H, Ph-H),
13
8.7 (br, 2H, NH2, D2O exchangeable); C-NMR (DMSO-d6): δ = 162.6, 149.0, 148.9, 139.9, 130.4,
129.8, 127.2, 126.5, 123.1, 112.7; MS: m/z (%) 307 (M+, 100), 290 (15), 95 (50), 77 (25).
8-Oxo-4-phenyl-4,8-dihydro-1-oxa-4,5,9-triaza-cyclopenta[a]naphthalene-7-carbothioic acid amide (16d).
Deep brown crystal from ethanol, yield 95%; m.p. 220 °С; Anal. Calcd. for C16H10N4O2S (322):
C, 59.62; H, 3.13; N, 17.38. Found: C, 59.40; H, 3.0; N, 17.3. IR (KBr): υmax: 1,638 (CO), 1,620 (CN);
13C-NMR (DMSO-d6): δ = 164.0, 155.0, 146.7, 143.0, 141.0, 129.3, 118.5, 115.1, 110.0; MS: m/z (%)
323 (M+, 25), 305 (75), 289 (60), 95 (80), 51 (40).
7-(1H-Benzoimidazol-2-yl)-4-phenyl-4H-1-oxa-4,5,9-triaza-cyclopenta[a]n-aphthalen-8-one (16g). Yellow
crystals from ethanol, Yield 98%; m.p. 278 °С; Anal. Calcd. for C22H13N5O2 (379): C, 69.65; H, 3.45;
N, 18.46. Found: C, 69.59; H, 3.41; N, 18.42; IR (KBr): υmax: 1,614 (CN), 1,670 (CO); 13C-NMR
(DMSO-d6): δ = 151.9, 149.1, 148.7, 146.9, 138.8, 129.2, 128.4, 126.5, 123.0, 120.9, 112.7; MS: m/z
(%) 380 (M+, 100), 286 (15), 195 (25), 95 (50), 77 (20).
7-Benzothiazol-2-yl-4-phenyl-4H-1-oxa-4,5,9-triazacyclopenta[a]naphthalen-8-one (16h). Orange crystals
from ethanol, yield 98%; m.p. 258 °С; Anal. Calcd. for C18H14N4O3 (396): C, 66.6; H, 3.05; N, 14.13.
1
Found: C, 66.59; H, 3.00; N, 14.12; IR (KBr): υmax: 1,614 (CN), 1,680 (CO); H-NMR (DMSO-d6):
δ = 6.7 (s, 1H, furan-H); 7.3 (s, 1H, furan-H); 7.4–7.7 (m, 9H, Ph-H); 8.6 (s, 1H, nicotine-H);
13C-NMR (DMSO-d6): δ = 158.8, 151.4, 151.4, 149.0, 148.9, 148.8, 140.1, 140.0, 137.8, 131.0, 130.4,
129.8, 126.6, 126.6, 125.7, 123.3, 123.1, 122.1, 121.6, 112.8; MS: m/z (%) 397 (M+, 100), 303 (5),
212 (10), 95 (40), 77 (10).
4-Phenyl-7-(4-phenylthiazol-2-yl)-4H-1-oxa-4,5,9-triaza-cyclopenta[a]naphthalen-8-one (16k). Yellow
crystals from ethanol, yield 98%; m.p. 230 °С; Anal. Calcd. for C24H14N4O2S(422): C, 68.23; H, 3.34;
N, 13.26. Found: C, 68.19; H, 3.21; N, 13.12; IR (KBr): υmax: 1,614 (CN), 1,680 (CO); 13C-NMR

Molecules 2012, 17
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(DMSO-d6): δ = 164.0, 155.0, 154.0, 146.7, 143.0, 139.0, 136.2, 129.3, 128.0, 127.0, 118.0, 115.1,
114.0, 110.0; MS: m/z (%) 423 (m+, 100), 329 (5), 238 (5), 95 (25), 77 (10).
8-Oxo-4-phenyl-4,8-dihydro-1-oxa-4,5,9-triazacyclopenta[a]naphthalene-7-carboxylic acid benzylidene
hydrazide (16l). Orange crystals from ethanol, yield 98%; m.p. 266 °С; Anal. Calcd. for C23H15N5O3
(409): C, 67.48; H, 3.69; N, 17.11. Found: C, 67.45; H, 3.59; N, 17.00; IR (KBr): υmax: 1,559 1,614
1
(CN), 1,680 (CO); H-NMR (DMSO-d6): δ = 6.7 (s, 1H, CH); 7.2 (s,1H, nicotine-H); 7.4–7.5 (t, 2H,
furan-H); 7.7–8.3 (m, 10H, Ph-H); 13C-NMR (DMSO-d6): δ = 130.5, 128.8, 127.4, 112.8, 106.4, 55.8,
18.9; MS: m/z (%) 410 (M+, 50), 291 (10), 105 (5), 77 (10).
4. Conclusions
In conclusion it has been found that 5 condenses with 1a to yield pyridazinones 7 as indicted from
13
the presence of a carbonyl carbon as δ = 165 ppm in the C-NMR. Initially formed imines 6 in this
case are readily hydrolysed under the reaction conditions to yield the final products. In fact this finding
supports our belief that heterocyclic imines like 6 are difficult to isolate as they readily afford the more
stable aromatic derivative.
Supplementary Materials
Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/17/5/5924/s1.
Acknowledgments
The authors are grateful to the Kuwait University Research Administration for financial support of
project SC 01/10, Analytical facitities provided by SAF projects No. GS 01/01 & GS 01/03 & GS
01/05 are greatly appreciated. Omnia Sayed Zaky is grateful to The Chemistry Department, Faculty of
Science at Qena, South Valley University for supporting her Ph.D. study.
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Sample Availability: Samples of the all compounds are available from the authors.
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(http://creativecommons.org/licenses/by/3.0/).