Efficient synthesis of 3-aroylcinnolines from aryl methyl ketones

Article abstract of DOI:10.1016/S0040-4020(00)01141-8

An efficient synthesis of 3-aroylcinnolines starting from the appropriate aryl methyl ketones is described. The latter were converted in two steps to the corresponding 3-oxo-3-aryl-2-arylhydrazonopropanals, which upon acid catalyzed cyclization in conc. s

Full text of DOI:10.1016/S0040-4020(00)01141-8

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 1609±1614
Ef®cient synthesis of 3-aroylcinnolines from aryl methyl ketones
Nouria A. Al-Awadi,p Mohamed Hilmy Elnagdi, Yehia A. Ibrahim,
Kamini Kaul and Ajith Kumar
Department of Chemistry, Kuwait University, P.O. Box 5969, Safat 13060, Kuwait
Received 20 September 2000; revised 14 November 2000; accepted 30 November 2000
AbstractÐAn ef®cient synthesis of 3-aroylcinnolines starting from the appropriate aryl methyl ketones is described. The latter were
converted in two steps to the corresponding 3-oxo-3-aryl-2-arylhydrazonopropanals, which upon acid catalyzed cyclization in conc. sulfuric
acid or polyphosphoric acid (PPA) led to the corresponding 3-aroylcinnolines. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
and to our knowledge the route has been adopted only a few
times in the last 40 years.8±12 Moreover, cyclization of the
monophenylhydrazones of benzil and 4,6-dimethyl-1,2-
cyclohexanedione in sulfuric acid was reported more than
half a century ago. However, no further report for the appli-
cation of this procedure to other derivatives was reported.13
Signi®cant commercial interest in the development of
benzopyridazine derivatives, particularly pharmaceutical
uses of pyridazines and cinnolines is shown by the large
number of patents ®led in this area.1 For example cin-
oxacine 12 is a cinnoline analogue of quinoline antibac-
terials used for urinary tract infection and ICI-D-7569 23
is an anxiolytic agent (Scheme 1).
2. Results and discussion
In conjunction with our recent interest in the synthesis of
benzopyridazines4,5 as potential pharmaceuticals, samples
of 3-aroylcinnolines with different functional substituents
on the benzo moiety were required. The main synthetic
route to cinnolines is the cyclization of o-substituted aryl-
hydrazones6 or diazotization of o-substituted anilines.7 Both
approaches cannot be readily adopted for preparing 3-acyl
and/or 3-aroylcinnolines with functional substituents on
the benzo moiety of the molecule. Although cyclization of
functionally substituted arylhydrazones, readily obtained
via coupling of diazotised aromatic amines with 1,3-bifunc-
tionally substituted methylenes, is a very interesting
approach that would enable synthesis of the required deriva-
tives, the scope of this synthetic route has not been de®ned
In the present work we describe an ef®cient synthesis of 3-
aroylcinnolines 5 by the acid catalyzed cyclization of 3-oxo-
3-aryl-2-arylhydrazonopropanals 4. This reaction represents
an easy access to 3-aroylcinnolines 5 of potential biological
applications. Although the synthesis of 3-acetylcinnolines
was reported a long ago,12 its application and generality to
other derivatives has not been followed up. Moreover, it
constitutes a tedious, low yielding and long procedure.
The present method offers an ef®cient, simple and general
synthetic procedure for 3-acylcinnoline and its substituted
derivatives, thus, complementing the few known literature
procedures for the synthesis of other cinnoline derivatives.
The required 2-arylhydrazonopropanals 4a±i were prepared
as described previously via coupling diazotised aromatic
amines with the enaminones 3a±g in ethanolic sodium
hydroxide solution.14 Compounds 4 were shown based on
1H NMR and 13C NMR to exist as a mixture of anti and syn
hydrazones with the anti form always prevailing as shown in
Table 1. The starting enaminones 3 were readily obtained
from the appropriate aryl methyl ketones.
Thus, heating the hydrazones 4a,b,d,e,h,i with conc. H2SO4
at 1008C for 3±5 m afforded good yields of the correspond-
ing cinnoline derivatives 5a,b,d,e,h,i,j. However, similar
treatment of the other hydrazones 4c,f,g led to the formation
of a mixture of the corresponding cinnoline together with
other sulfonation products from which a pure product was
Scheme 1.
Keywords: 2-arylhydrazono-3-oxopropanal; cinnolines; aryl methyl
ketones.
p
Corresponding author. Tel.: 1965-4845098; fax: 1965-4836127;
e-mail: nouria@kuc01.kuniv.edu.kw
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01141-8

1610
N. A. Al-Awadi et al. / Tetrahedron 57 (2001) 1609±1614
Table 1. NMR (DMSO-d6) data for the hydrazones 4a±i and the respective aldehydic CHO in 1H NMR
1H NMR d
13C NMRa d
Product anti, syn %
4a 78, 22
Molecular formula
anti, syn CHO, NH (s)
Other H's
C15H12N2O2 (252.27)
10.02, 14.1 9.56, 12.3
7.18±7.89 (m, 10 H)
116.5, 117.5, 125.2, 126.8,
128.8, 129.6, 129.9, 130.2,
130.4, 130.9, 132.9, 133.0,
134.8, 137.1, 137.9, 138.7,
142.3, 143.2, 189.1, 189.6,
191.8, 193.2
4b 85, 15
4c 78, 22
C15H11N2ClO2 (286.5)
9.99, 14.35 9.52, 12.69
9.96, 14.2 9.54, 11.85
7.22±7.91 (m, 9H)
116.7, 117.7, 125.5, 126.9,
128.9, 129.7, 130.3, 130.5,
131.7, 132.8, 135.9, 136.6,
137.8, 138.0, 139.6, 142.3,
143.0, 188.9, 189.6, 190.6, 193.0
56.35, 56.57, 114.2, 115.1,
116.2, 117.4, 124.7, 126.6,
129.7, 130.0, 130.2, 130.5,
132.6, 133.2, 133.4, 140.1,
142.4, 143.4, 163.5, 165.0,
189.3, 189.6, 189.9, 191.5
117.9, 124.0, 127.2, 130.5,
131.9, 132.7, 142.1, 143.9,
149.9, 188.6, 190.8
113.5, 114.1, 116.4, 117.8,
122.5, 123.4, 125.1, 126.9,
130.2, 130.6, 132.5, 138.3,
142.2, 143.2, 148.8, 150.3,
150.6, 152.3, 177.5, 178.4,
188.6, 189.2
C16H14N2O3 (282.5)
7.07±7.49 (m, 9H),
3.87 (s, 3H, OCH3)
4d 79, 11
4e 86, 14
C15H11N3O4 (297)
10.05, 14.28 9.5, 12.5
9.95, 14.31 9.51, 12.11
7.05±8.39 (m, 9H)
6.79±8.11 (m, 8H)
C13H10N2O3 (242.2)
4f 95, 5
C13H10N2O2S (258.3)
C16H14N2O3 (282.5)
9.99, 14.35 9.50, 12.18
9.99, 14.44 9.51, 12.78
7.24±8.06 (m, 8H)
116.4, 118.1, 125.0, 127.0,
128.7, 129.9, 130.2, 130.6,
132.6, 135.9, 136.7, 137.3,
138.1, 139.6, 142.2, 143.6,
181.5, 182.0, 188.9, 189.3
56.9, 115.5, 115.7, 118.3, 119.1,
128.7, 129.3, 129.8, 130.8,
132.3, 132.7, 134.3, 135.6,
136.4, 136.8, 137.6, 138.2,
157.7, 158.7, 188.5, 189.2,
191.7, 192.6
4g 78, 22
6.98±7.87 (m, 9H),
3.75 (s, 3H, OCH3)
4h 45, 55
4i 67, 33
C15H11N3O4 (297)
10.01, 13.9 9.63, 12.1
7.59±8.23 (m, 9H)
7.14±7.9 (m, 9H)
115.8, 117.5, 126.4, 126.5,
129.0, 130.0, 130.0, 131.1,
133.5, 134.6, 135.8, 135.9,
137.3, 143.2, 143.3, 144.6,
148.2, 149.1, 189.6, 190.2,
191.7, 193.6
114.9, 115.7, 116.2, 117.3,
124.3, 126.1, 128.8, 129.8,
129.9, 130.9, 131.9, 132.1,
133.1, 133.3, 134.8, 134.9,
135.3, 136.5, 137.7, 140.5,
144.2, 189.2, 189.9, 191.9, 193.4
C15H11N2ClO2 (286.5)
10.17, 14.15 9.58, 12.08
a
Signals due to both anti and syn isomers, compound 4d showed signals assignable for the major anti isomer due to solubility reason.
1
dif®cult to isolate. Replacing sulfuric acid with poly-
phosphoric acid overcame this problem. Thus, successful
conversion of 4c,f,g into the corresponding cinnoline
derivatives 5c,f,g was readily achieved in good yields
by heating with PPA at 100±1208C for 8±10 m. Cycli-
zation of the m-chlorophenylhydrazones 4i gave as
expected a mixture of the corresponding 3-benzoyl-5-
chlorocinnolines 5i and its isomeric 7-chloro derivative
signal assignment of 5a was made using H NMR, NOE-
difference spectra, H,H-COSY, HMQC and HMBC NMR
techniques. Thus, from 1H NMR, H-4 was readily assigned
at d 8.87 (s, 1H). By irradiation at H-4 from NOE-difference
experiment H-5 was assigned at d 8.3 (showed highest NOE
enhancement). From these assignments and H,H-cosy, other
protons were readily assigned by examining the different
cross peaks. Thus, H-6, H-7, H-8 were assigned at d 8.0
(t, 1H), 8.15 (t, 1H), 8.6 (d, 1H), respectively. The phenyl
protons H-11, H-12, H-13 were assigned at d 8.04 (d, 2H),
7.6 (t, 2H), 7.75 (t, 1H), respectively. Similarly the different
cinnoline protons of other derivatives were assigned as
shown in Table 2. It was found in HMBC experiment that
cross peaks appear only for 3-bond H±C coupling. From
decoupled 13C NMR, DEPT-CH, HMQC and HMBC the
1
5j in about a 1:9 ratio as determined from the H NMR
spectra of the mixture obtained. From this mixture a pure
sample of 5j was obtained by fractional crystallization
(Scheme 2).
The structure of the formed cinnolines was con®rmed by 1H
NMR and 13C NMR spectroscopy. Full proton and carbon

Table 2. NMR (DMSO-d6) data for the cinnolines 5a±j
Product
Molecular formula
1H NMR d multiplicity, J(Hz)
13C NMR d
H-4
H-5
H-6
H-7
H-8
Other H's
5a
5b
5c
5d
5e
C15H10N2O (234)
C15H9N2ClO (268.5)
C16H12N2O2 (264)
C15H9N3O3 (279)
C13H8N2O2 (224)
8.88 s
8.32 d, 8.0
8.01 t, 7.5
8.13 t, 8.0
8.16 t, 8.0
8.11 t, 8.0
8.18 t, 8.2
8.10 t, 8.6
8.61 d, 8.2
8.62 d, 8.5
8.61 d, 8.4
8.63 d, 8.7
8.58 d, 8.5
8.05, 7.74, 7.61 d, 7.2, t, 7.3, t,
7.5
126.2, 126.3, 129.3, 129.5,
129.8, 131.8, 133.1, 134.2,
134.3, 137.0, 151.2, 152.4, 193.6
126.4, 129.4, 126.6, 129.9,
133.2, 133.7, 134.3, 135.8,
139.8, 139.2, 151.2, 152.1, 192.3
56.5, 114.7, 125.8, 126.4, 129.4,
129.5, 129.8, 133.0, 133.9,
134.4, 151.1, 153.1, 164.4, 191.7
124.2, 126.3, 126.7, 129.7,
129.9, 132.9, 133.3, 134.7,
142.5, 150.6, 151.3, 151.4, 192.6
113.9, 125.4, 126.0, 126.3,
129.6, 129.8, 133.1, 134.2,
150.3, 151.38, 151.42, 151.5,
178.1
8.91 s
8.81 s
9.01 s
8.82 s
8.34 d, 8.0
8.3 d, 8.0
8.37 d, 8.1
8.29 d, 8.6
8.02 t, 7.6
8.02 t, 7.5
8.04 t, 8.0
7.97 t, 7.9
8.13, 7.69 d, 8.5, d, 8.5
8.10, 7.14, 3.8 d, 7.0, d, 7.0, s
8.42, 8.29 d, 8.8, d, 8.8
8.23, 8.11, 6.89 d, 1.2, d, 3.5, dd,
3.5, 1.3
5f
C13H8N2OS (240)
8.95 s
8.34 d, 8.2
8.01 t, 7.5
8.14 t, 7.22
8.62 d, 8.2
8.45, 8.23, 7.37 dd, 3.9, 1.0, dd,
4.8, 1.0 dd, 4.8, 3.9
125.7, 126.5, 129.3, 129.7,
1229.8, 133.2, 134.4, 138.4,
139.0, 140.9, 151.3, 151.5, 182.5
5g
5h
C16H12N2O2 (264)
C15H9N3O3 (279)
8.62 s
9.2 s
7.6 s
8.87 d, 9.3
-
-
7.7 d, 8.6
8.75 dd, 9.2, 2.4
8.51 d, 8.8
9.39 d, 2.3
8.19, 7.73, 7.6 d, 8.0, t, 7.8, t, 7.6
8.07, 7.77, 7.63 d, 7.5, t, 7.6, t,
7.6
126.2, 126.9, 127.1, 128.1,
129.4, 131.8, 132.4, 134.6,
136.7, 149.1, 151.3, 153.4, 193.1
5i*
C15H9N2ClO (268)
C15H9N2ClO (268)
8.7 s
-
8.21 d, 8.2
8.05 d, 8.2
8.14 t, 8.3
-
8.65 d, 8.6
8.75 s
8.07, 7.74, 7.61 d, 7.8, t, 7.5, t,
7.6
8.05, 7.74, 7.62 d, 8.3, t, 7.3 t,
7.6
5j
8.95 s
8.41 d, 8.2
125.2, 126.2, 128.5, 129.3,
131.8, 133.9, 134.4, 136.9,
138.5, 151.2, 152.7, 193.3

1612
N. A. Al-Awadi et al. / Tetrahedron 57 (2001) 1609±1614
Scheme 2.
different carbon signals of 5a were assigned at d 152.4 (C-
3), 126.2 (C-4), 126.3 (C-4a), 129.5 (C-5), 133.0 (C-6),
134.2 (C-7), 129.8 (C-8), 151.2 (C-8a), 193.6 (C-9), 137.0
(C-10), 131.8 (C-11), 129.3 (C-12), 134.3 (C-13).
nucleophilic attack by the aromatic ring of the hydrazone
moiety on the formyl carbonyl carbon (7 to 8), followed by
elimination of water to give 5 (Scheme 3). Alternatively,
one may assume initial isomerization of 7 into 9 which then
undergoes 6p electrocyclization also yielding 8 via a quasi
aromatic six membered transition state followed by dehydra-
tion to yield the corresponding cinnoline derivative 5. Kinetic
study of this acid catalyzed cyclization as well as gas phase
pyrolytic cyclization including substituents effect proved that
the second pathway is more favorable and details of this study
will be the subject of another publication. Moreover, ¯ash
vacuum pyrolysis of the hydrazones 4 into the cinnolines 5
is now under investigation and will be reported soon.
2.1. Mechanism of the acid catalyzed cyclization of 2
Two mechanistic pathways may be suggested to account for
the acid catalyzed conversion of 4 into 5. Both start with
protonation of 4 to 7. The ®rst mechanism involves a
3. Experimental
Melting points are uncorrected. IR: (KBr) Shimadzu IR-740

N. A. Al-Awadi et al. / Tetrahedron 57 (2001) 1609±1614
1613
Scheme 3.
1
spectrometer. H and 13C NMR: Bruker Avance 400 spec-
trometer. Ms: Gc/Ms INCOS XL Finnigan MAT. Micro-
analysis: LECO CHNS-932.
3.1.5. 3-(2-Furyl)-3-oxo-2-phenylhydrazonopropanal
(4e). From aniline and 3e. Yield 1.72 g (71%); mp 114±
1168C (Lit.14 115±1168C).
3.1.6. 3-Oxo-2-phenylhydrazono-3-(2-thienyl)propanal
(4f). From aniline and 3f. Yield 1.9 g (74%); mp 114±
1158C (Lit.14 113±1158C).
3.1. 2-Arylhydrazono-3-oxopropanal 4a±i; General
procedure
3.1.7. 3-Oxo-3-phenyl-2-(4-methoxyphenylhydrazono)-
propanal (4g). From p-anisidine and 3a. Yield 2.0 g
(71%); mp 102±1038C. IR: 3435, 3084, 3009, 2968, 2855,
1645, 1631, 1607 cm21. Anal. Calcd For C16H14N2O3:
C, 68.08; H, 4.96; N, 9.93. Found: C, 68.25, H, 5.01, N,
9.95.
A cold solution of the diazonium salt (10 mmol) (prepared
by adding a cold solution of sodium nitrite (0.7 g) in water
(5 mL) to a solution of the appropriate arylamine (10 mmol)
in conc HCl (5 mL)) was added to a cold solution of the
appropriate enaminones 3 in EtOH (50 mL) containing
NaOH (1.6 g). The mixture was then stirred at room
temperature for 1 h, and the solid precipitated was collected
and crystallized from EtOH.
3.1.8. 3-Oxo-3-phenyl-2-(4-nitrophenylhydrazono)pro-
panal (4h). From p-nitroaniline and 3a. Yield 2.16 g
(73%); mp 143±1458C. IR: 3435, 3116, 3089, 2989, 1646,
1650 1596 cm21. Anal. Calcd For C15H11N3O4:C, 60.61; H,
3.70; N, 14.14. Found: C, 60.66, H, 3.88, N, 14.21.
3.1.1. 3-Oxo-3-phenyl-2-phenylhydrazonopropanal (4a).
From aniline and 3a. Yield 1.96 g (78%); mp 82±848C
(Lit.14 mp 82±848C).
3.1.9. 3-Oxo-3-phenyl-2-(3-chlorophenylhydrazono)pro-
panal (4i). From m-chloroaniline and 3a. Yield 1.8 g
(65%); mp 141±1438C. IR: 3435, 3074, 3024, 2981, 1651,
1637, 1592 cm21. Anal. Calcd For C15H11ClN2O2: C, 62.82;
H, 3.84; N, 9.77. Found: C, 63.09, H, 4.03, N, 9.77.
3.1.2.
3-Oxo-3-(4-chlorophenyl)-2-phenylhydrazono-
propanal (4b). From aniline and 3b. Yield 2.15 g (75%);
mp 135±1378C. IR: 3423, 3023, 2905, 2781, 1648,
1636 cm21. Anal. Calcd For C15H11ClN2O2: C, 62.82; H,
3.84; N, 9.77. Found: C, 62.79, H, 4.05, N, 9.82.
3.2. 3-Aroylcinnolines 5a±j; General procedures
3.1.3. 3-Oxo-3-(4-methoxyphenyl)-2-phenylhydrazono-
propanal (4c). From aniline and 3c. Yield 2.03 g (72%);
mp 141±1438C. IR: 3430, 3170, 2968, 2865, 2795, 1649,
1624, 1607 cm21. Anal. Calcd For C16H14N2O3: C, 68.08; H,
4.96; N, 9.93. Found: C, 67.84, H, 4.96, N, 9.72.
(A) A mixture of the appropriate 3-oxo-2-arylhydrazono-
propanal 4 (1.5 g) in conc. H2SO4 (20 mL) was heated at
1008C for 3±5 m. After cooling and dilution with cold
water the precipitate was collected, washed with water
and recrystallized from ethanol.
3.1.4. 3-Oxo-3-(4-nitrophenyl)-2-phenylhydrazonopro-
panal (4d). From aniline and 3d. Yield 2.15 g (75%); mp
173±1758C. Anal. Calcd For C15H11N3O4: C, 60.61; H,
3.70; N, 14.14. Found: C, 60.36, H, 3.80, N, 13.84.
(B) A mixture of the appropriate 3-oxo-2-arylhydrazono-
propanal 4 (1.5 g) and polyphosphoric acid (20 mL) was
heated at 100±1208C for 8±10 m. After cooling and dilu-
tion with cold water the precipitate was collected, washed

1614
N. A. Al-Awadi et al. / Tetrahedron 57 (2001) 1609±1614
with water and recrystallized from ethanol using charcoal
to remove charring materials.
IR: 3065, 2924, 1641, 1625, 1595, 780, 720 cm21. Anal.
Calcd For C15H9N3O3: C, 64.51; H, 3.25; N, 15.05.
Found: C, 64.16, H, 3.53, N, 14.62.
3.2.1. 3-Benzoylcinnoline 5a. Yellow crystals from 4a
using procedure A. Yield 0.84 g (60%); mp 138±1398C.
Ms: m/z 234 (85, M1), 206 (60%), 178 (40%), 129 (5%),
105 (65%), 101 (25%), 77 (100%). IR: 3055, 1661, 1615,
1599, 755, 697 cm21. Anal. Calcd For C15H10N2O: C, 76.92;
H, 4.27; N, 11.96. Found: C, 76.65, H, 4.46, N, 11.77.
3.2.9. 3-Benzoyl-7-chlorocinnoline 5j. Lemon yellow
¯akes from 4i using procedure A. Yield 0.7 g (50%); mp
181±1838C. Ms: m/z 268, 270 (60%, 20%, M1), 242 (15%),
240 (45%), 214 (7%), 212 (20%), 165 (1%). 163 (3%), 137
(5%), 135 (15%), 105 (70%), 77 (100%). IR: 3080, 3056,
1663, 1609, 1599, 779, 714 cm21. This compound was
isolated from the reaction mixture containing also the 5-
chloro-isomer 5i by fractional crystallization. The ratio of
3.2.2. 3-(4-Chlorobenzoyl)cinnoline 5b. Pale yellow crys-
tals from 4b using procedure A. Yield 0.7 g (50%); mp
152±1548C. Ms: m/z 268, 270 (95%, 35%, M1), 240
(3%), 242 (1%), 212 (10%), 214 (3%), 139 (85%), 141
(30%), 129 (5%), 111 (95%), 113 (35%), 101 (25%). IR:
3054, 1661, 1615, 1589, 755, 697 cm21. Anal. Calcd For
C15H9ClN2O: C, 67.03; H, 3.35; N, 10.42. Found: C, 66.64,
H, 3.51, N, 10.29.
1
the two isomers in the mixture as determined by H NMR
was 90:10 of 5j, 5i, respectively. Anal. Calcd For
C15H9ClN2O (5j): C, 67.03; H, 3.35; N, 10.42. Found: C,
66.74, H, 3.53, N, 10.25.
Acknowledgements
3.2.3. 3-(4-Methoxybenzoyl)cinnoline 5c. Yellow crystals
from 4c using procedure B. Yield 0.77 g (55%); mp 189±
1918C. Ms: m/z 264 (95%, M1), 236 (25%), 208 (5%), 135
(100%), 129 (5%), 107 (20%), 101 (10%). IR: 3096, 2973,
1647, 1596, 799, 765 cm21. Anal. Calcd For C16H12N2O2: C,
72.71; H, 4.58; N, 10.60. Found: C, 72.42, H, 4.83, N, 10.42.
The support of the University of Kuwait received through
research grant no. SC091 and the facilities of ANALAB and
SAF are gratefully acknowledged.
References
1. Heinisch, H.; Frank, H. Progress in Medicinal Chemistry.
Ellis, G. P., West, G. G., Eds.; Elsevier: Amsterdam, 1990.
2. Coates, W. G. In Pyridazines and their Condensed Deriva-
tives, Katritzky, A. R., Rees, C. W., Scriven, F. V., Eds.; In
Comprehensive Heterocyclic Chemistry II, Pergamon:
London, 1996; Vol. 6, pp 87.
3.2.4. 3-(4-Nitrobenzoyl)cinnoline 5d. Buff powder from
4d using procedure A. Yield 0.84 g (60%); mp 210±2128C.
Ms: m/z 279 (100%, M1), 251 (35%), 223 (8%), 150 (36%),
129 (6%), 101 (28%). IR: 3111, 3082, 1658, 1599, 797,
750 cm21. Anal. Calcd For C15H9N3O3: C, 64.51; H, 3.25;
N, 15.05. Found: C, 64.16, H, 3.53, N, 14.67.
3. Melikian, A.; Schlewer, G.; Chambon, J. P.; Wermuth, C. G.
J. Med. Chem. 1992, 35, 4092±4097.
3.2.5. 3-(2-Furoyl)cinnoline 5e. Yellow crystals from 4e
using procedure A. Yield 0.77 g (55%); mp 181±1838C.
Ms: m/z 224 (45%, M1), 196 (70%), 168 (100%), 129
(10%), 101 (30%), 95 (95%), 67 (10%). IR: 3160, 3058,
1644, 1634, 1616, 1559, 766, 751 cm21. Anal. Calcd For
C13H8N2O2: C, 69.64; H, 3.57; N, 12.50. Found: C, 69.37, H,
3.66, N, 12.31.
4. Al-Awadhi, H.; Al-Omran, F.; Elnagdi, M. H.; Infantes, L.;
Foces-Foces, C.; Jagerovic, N.; Elguero, J. Tetrahedron 1995,
51, 12745±12762.
5. Al-Omran, F.; Khalik, M. M. A.; Al-Awadhi, H.; Elnagdi,
M. H. Tetrahedron 1996, 52, 11915±11928.
6. Newkome, G. R.; Paudler, W. W.; Contemporary Hetero-
cyclic Chemistry: Synthesis, Reactions and Applications.
John Wiley & Sons, New York, 1982; pp. 214±215 and
references cited therein.
3.2.6. 3-(2-Thienoyl)cinnoline 5f. Pale yellow plates from
4f using procedure B. Yield 0.84 g (60%); mp 140±1428C.
Ms: m/z 240 (45%, M1), 212 (50%), 184 (30%), 129 (5%),
111 (100%), 101 (20%), 83 (35%). IR: 3060, 1631, 1618,
793, 723 cm21. Anal. Calcd For C13H8N2OS: C, 65.00; H,
3.33; N, 11.66; S, 13.33. Found: C, 64.75, H, 3.49, N, 11.62;
S, 13.60.
7. (a) Bruce, J. M. J. Chem. Soc. 1959, 2366±2375. (b) Besford,
L. S.; Bruce, J. M. J. Chem. Soc. 1964, 4037±4044.
8. Barber, H. J.; Washbourn, K.; Wragg, W. R.; Lunt, E. J. Chem.
Soc. 1961, 2828±2843.
9. Condensed Pyridazines including Cinnolines and Phthala-
zines, Castle, R. N., Ed.; Wiley Interscience: New York, 1973.
10. Kanner, C. B.; Pandit, U. K. Tetrahedron 1981, 37, 3513±
3518.
3.2.7. 3-Benzoyl-6-methoxycinnoline 5g. Yellow crystals
from 4g using procedure B. Yield 0.49 g (35%); mp 195±
1978C. Ms: m/z 264 (95%, M1), 236 (25%), 208 (2%), 159
(2%), 131 (5%), 105 (100%), 77 (100%). IR: 3062, 1656,
1618, 1598, 764, 699 cm21. Anal. Calcd For C16H12N2O2: C,
72.71; H, 4.58; N, 10.60. Found: C, 72.49, H, 4.63, N, 10.40.
11. Gewald, K.; Calderon, O.; Shaefer, H.; Hain, U. Liebigs Ann.
Chem. 1984, 1390±1394.
12. Baumgarten, H. E.; Anderson, C. H. J. Am. Chem. Soc. 1958,
80, 1981±1984.
13. Moore, B. P. Nature 1949, 163, 918±919.
14. Al-Omran, F.; Abdel Khalik, M. M.; Abou-Elkhair, A.;
Elnagdi, M. H. Synthesis 1997, 91±94.
3.2.8. 3-Benzoyl-6-nitrocinnoline 5h. Yellow crystals from
4h using procedure A. Yield 0.7 g (50%); mp 188±1908C.