Enaminones in heterocyclic synthesis: A new regioselective synthesis of 2,3,6-trisubstituted pyridines, 6-substituted-3-aroylpyridines and 1,3,5-triaroylbenzenes

Article abstract of DOI:10.1002/jhet.5570390528

1-Substituted-3-dimethylaminopropenones 1a-d reacted with acetylacetone and with ethyl acetoacetate to yield regioselectively 2,3,6-trisubstituted pyridines. Refluxing 1a-d in acetic acid/ammonium acetate resulted in the formation of 6-substituted-3-aroylpyridines, whereas refluxing in acetic acid alone afforded 1,3,5-triaroylbenzene.

Full text of DOI:10.1002/jhet.5570390528

Sep-Oct 2002
Enaminones in Heterocyclic Synthesis: a New Regioselective
Synthesis of 2,3,6-Trisubstituted Pyridines, 6-Substituted-3-
Aroylpyridines and 1,3,5-Triaroylbenzenes
1035
Balkis Al-Saleh [a], Mervat Mohammed Abdelkhalik [b],
Afaf Mohammed Eltoukhy [b], and Mohammed Hilmy Elnagdi *[c]
[a] Department of Chemistry, Faculty of Science, University of Kuwait, P. O. Box 5969 Safat, 13060 Kuwait
[b] Department of Chemistry, Girls College for Arts, Science and Education, Ain Shams University,
P. O. Box 11757 Heliopolis, Cairo, A. R. Egypt
[c] Department of Chemistry, Faculty of Science, Cairo University, Giza, A. R. Egypt
e-mail: Shelmy@access.com.eg
Received March 13, 2002
1-Substituted-3-dimethylaminopropenones 1a-d reacted with acetylacetone and with ethyl acetoacetate to
yield regioselectively 2,3,6-trisubstituted pyridines. Refluxing 1a-d in acetic acid/ammonium acetate
resulted in the formation of 6-substituted-3-aroylpyridines, whereas refluxing in acetic acid alone afforded
1,3,5-triaroylbenzene.
J. Heterocyclic Chem., 39, 1035 (2002).
1
Enaminones are readily obtainable, versatile reagents
and their chemistry has recently received considerable
attention [1-3]. In conjunction with our interest in exploring
the synthetic potential of 1-substituted-3-dimethylamino-
propenones 1a-d we report here efficient syntheses of
2,3,6-trisubstituted pyridines, 6-substituted-3-aroylpyri-
dines and of 1,3,5-triaroylbenzenes utilizing 1a-d as start-
ing materials. 2,3,6-Trisubstituted pyridines have found
extensive utility as pharmaceuticals, e.g., 2,6-diamino-3-
phenylazopyridine is used as antibacterial for urinary tract
infection [4]. Synthetic approaches to pyridines are well
documented [5,6]. Moreover, several 2,3,6-trisubstituted
pyridines have previously been synthesized via reacting
1-substituted-3-dimethylaminopropanone hydrochlorides
with β-aminovinyl ester [7] and 2-substituted-5-aroyl-
pyridines have been obtained earlier via reacting hydroxy-
methyleneacetophenone with ammonia [8].
difference experiments. For example, the H NMR spectra
of compound 4a revealed two singlets at δ = 2.65 and 2.92
ppm for the acetyl and methyl protons, along with two
doublets at δ = 7.80 and 8.10 ppm J = 8.0 Hz for pyridine
H-5 and H-4. 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]. Moreover, irradiating the signal at δ
= 8.10 ppm enhanced the acetyl methyl signal at δ = 2.65
ppm and vice versa (Scheme 1).
Scheme 1
Compounds 1a,b reacted readily with acetylacetone in
refluxing acetic acid and in the presence of ammonium
acetate to yield a product that may be formulated as 4a,b
or 5a,b. Thus initial addition of active methylene moiety to
the α,β-unsaturated double bond in 1 would yield the
Michael adduct 2 that cyclizes in the presence of ammo-
nium acetate into 4. Alternately initial condensation of
active methylene moiety with carbonyl function would
yield 3 which in the presence of ammonium acetate
cyclizes into 5. Although it is generally accepted that car-
banions initially add to the activated double bond in
enones [9], it has been recently shown that the situation is
different in the reaction of malononitrile with enaminones
and products resulting from either initial addition across
the activated double bond or at the carbonyl moiety has
been isolated. The outcome of the reaction has been shown
to depend on the applied reaction conditions [10,11].
Consequently conclusive structure elucidation for the
structure of products of reacting 1 with acetylacetone
seemed mandatory. Structure 4 could be established for the
The reaction of 1c,d was attempted with acetylacetone
under the same reaction conditions did not afford the
expected pyridines 4c,d. However, products 7c,d were
obtained. These are assumed to be formed via initial addition
of two molecules of 1c,d yielding intermediate 6 that
cyclises by action of ammonia into 7c,d [7]. Compounds
7b,d have been prepared earlier in the self-condensation
1
reaction product based on H NMR spectra and NOE

1036
B. Al-Saleh, M. M. Abdelkhalik, A. Mohammed Eltoukhy, and M. H. Elnagdi
Vol. 39
spectra were recorded on a Varian EM-390 400 MHz spectrometer
reaction of hydroxymethylenacetophenone in the presence of
2
in [ H ] DMSO as solvent and TMS as internal standard; chemi-
NH [8]. Although, reactivity of C-2 in enaminones toward
6
3
cal shifts are reported in δ units (ppm). Mass spectra were mea-
sured on MS 30 and MS 9 (AEI), 70 eV. Microanalyses were per-
formed on LECO CHNS-932. Microanalytical data were obtained
from the Microanalytical Data Unit at Cairo University The
authors are grateful to University of Kuwait R. A. for Analytical
Facilities provided by SAF through project Sc 101. Compounds
1a-d were prepared following published procedure [19].
nitrogen electrophiles have recently been reported [13-15], to
our knowledge only reaction of enaminones with 1,4-naph-
thoquinone has recently been reported [16]. In a trial to iso-
late intermediate 6, compounds 1c,d were refluxed in acetic
acid alone, however under this condition the triaroylbenzene
derivatives 9c,d were the only isolable products. It is most
likely that intermediate 6 reacted swiftly with a third mole-
cule of 1c,d yielding intermediate 8 that loses three mole-
cules of dimethylamine yielding the final product 9c,d. It is
3-Dimethylamino-1-naphthalen-2-yl-prop-2-en-1-one (1a).
This compound was obtained in 92% yield, 2.07 g; mp 106 °C;
-1
IR (KBr) ν
= 3425 (NMe ), 3054 (arom. CH), 1677 cm
1
max
2
interesting to report here that the H NMR spectra of this
+
1
(CO); MS (EI, 70 eV): m/z = 225 [M ]; H NMR (CDCl ): δ
=
H
3
symmetrically trisubstituted benzene, taking compound 9c as
typical example, showed a singlet for 3 protons at δ = 8.45
ppm for the three benzene protons. This excluded completely
the possibility of non-symmetrical substituted regioisomers
for this reaction product (Scheme 2).
3.18 (s, 3H, NCH ), 3.36 (s, 3H, NCH ), 5.90 (d, 1H, J = 12.3
3
3
Hz, H-2), 7.33-7.55 (m, 2H, arom. H) 7.86-8.05 (m, 5H; 4H
arom. H and 1H H-3), 8.49 (s, 1H, arom. H).
Anal. Calcd. for C
H NO (225.28): C, 79.97; H, 6.71; N,
15 15
6.22. Found: C, 80.20; H, 6.48; N 6.32.
1-(4-Chlorophenyl)-3-dimethylaminoprop-2-en-1-one (1b).
This compound was obtained in 90% yield, 1.90 g; mp 102 °C;
Scheme 2
IR (KBr) ν
= 3440 (NMe ), 3070 (arom. CH), 2970 (aliph.
max
2
-1
CH), 1646 (CO), 1600 cm (arom. C=C); MS (EI, 70 eV): m/z =
+
1
209 [M ]; H NMR (CDCl ): δ = 2.95 (s, 3H, NCH ), 3.14 (s,
3
H
3
3H, NCH ), 5.78 (d, 1H, J = 12.3 Hz, H-2), 8.01 (d, 2H, J = 8.1
3
Hz, arom-H), 8.05-8.21 (m, 3H, arom-H and H-3); (209.5).
Anal. Calcd. for C
H NOCl: C, 63.00; H, 5.72; N 6.68.
11 12
Found C 63.06, H 5.70, N 6.65.
3-Dimethylamino-1-p-tolylprop-2-en-1-one (1c).
This compound was obtained in 92% yield, 1.73 g; mp 94 °C; IR
(KBr) ν
= 3434 (NMe ), 3070 (arom. CH), 2970 (aliph. CH),
max
2
-1
1644 (CO), 1600 cm (arom.C=C); MS (EI, 70 eV): m/z = 189
+
1
[M ]; H NMR (CDCl ): δ = 2.40 (s, 3H, CH ), 2.93 (s, 3H,
3
H
3
NCH ), 3.13 (s, 3H, NCH ), 5.73 (d, 1H, J = 12.3 Hz, H-2), 7.22
3
3
(d, 2H, J = 8.0 Hz, arom-H), 7.79-7.83 (m, 3H, arom-H and H-3).
Anal.Calcd. for C NO (189.25): C, 76.15; H, 7.99; N,
H
12 15
7.40. Found: C, 76.15; H, 7.81; N, 7.59.
3-Dimethylamino-1-(4-methoxy-phenyl)-prop-2-en-1-one (1d).
This compound was obtained in 85% yield, 1.74 g (85%); M.
Similar to the behavior of 1c,d compounds 1a,b
afforded the pyridine derivatives 7a,b on reflux in acetic
acid and ammonium acetate, while 1a afforded the tri-
aroylbenzene 9a on reflux in acetic acid (Scheme 2).
Similar to the behavior of 1a,b with acetylacetone, com-
pounds 1a-d react with ethyl acetoacetate to yield the pyri-
dine derivatives 4e-h. Alternate isomeric structures 5e-h
p. 100 °C. IR (KBr) ν
= 3430 (NMe ), 3060 (arom. CH),
max
2
-1
2980 (aliph. CH), 1674 (CO), 1600 cm (arom.C=C); MS (EI, 70
+
1
eV): m/z = 205 [M ]; H NMR (CDCl ): δ = 2.56 (s, 3H, CH ),
3
H
3
2.94 (s, 3H, NCH ), 3.87 (s, 3H, NCH ), 5.72 (d, 1H, J = 12.3
3
3
Hz, H-2), 6.93 (d, 2H, J = 7.5 Hz, arom-H), 7.79 (d, 1H, J = 12.3
Hz, H-3), 7.93 (d, 1H, J = 7.5 Hz, arom. H).
1
were ruled out based on the H NMR, which revealed pyri-
Anal. Calcd. for C
H NO (205.25): C, 70.22; H, 7.37; N,
12 15 2
dine protons with a coupling constant value J 8.2 Hz,
that is typical for pyridine H-3 and H-4 [12] (Scheme 1).
Compounds 4f-h have also been obtained earlier from the
reaction of 1-aroyl-3-dimethylaminopropanone hydrochlo-
ride or hydroxymethylenacetophenone derivatives with
ethyl 3-aminocrotonate [7,17]. Some descriptions of 7 and 9
has been described in a recent communication [18]
6.82. Found: C, 69.98; H, 7.08; N, 6.80.
General Procedure for the Preparation of the Pyridine Derivatives
4a,b.
To a solution of each of the enaminone 1a-d (10 mmol) and
ammonium acetate (1 g) in acetic acid (10 ml), acetylacetone (1.2
g, 12 mmol) was added. The reaction mixture was heated under
reflux for 1 hour. The solvent was evaporated in vacuum; the
residual solid was crystallized from dioxane.
EXPERIMENTAL
1-(2-Methyl-6-naphthalen-2-yl-pyridin-3yl)ethanone (4a).
This compound was obtained in 82% yield, 2.14 g; mp 112 °C;
All melting points are uncorrected. IR spectra were recorded in
1
IR (KBr) ν
= 3050 (arom. CH), 2990 (aliph. CH), 1678 (CO),
KBr with a Pye Unicam SP 1100 spectrophotometer. H NMR
max

Sep-Oct 2002
Enaminones in Heterocyclic Synthesis
1037
-1
+
1
J = 7.5 Hz, OCH CH ), 7.28 (d, 2H, J = 8.2 Hz, phenyl-H), 7.81
1600 cm (arom.C=C); MS (EI, 70 eV): m/z = 261 [M ];
H
2
3
(d, 1H, J = 8.2 Hz, pyridyl H-5), 8.01 (d, 2H, J = 8.2 Hz, phenyl-
H), 8.16 (d, 1H, J = 8.2 Hz, pyridyl H-4).
NMR (CDCl ): δ = 2.65 (s, 3H, COCH ), 2.92 (s, 3H, CH ),
3
H
3
3
7.53-7.57 (m, 2H, naphthyl-H), 7.80 (d, 1H, J = 8.0 Hz, pyridyl
H-5), 7.88-7.92 (m, 1H; naphthyl-H), 7.96-8.02 (m, 2H, naph-
thyl-H), 8.10 (d, 1H, J = 8.0 Hz, pyridyl H-4), 8.21 (d, 1H, J =
Anal. Calcd. for C
H NO (255.30): C, 75.27; H, 6.71; N,
16 17 2
5.49. Found: C, 75.06; H, 6.74; N, 5.76.
13
8.5 Hz, naphthyl-H), 8.58 (s, 1H, naphthyl-H); C NMR
Ethyl 6-(4-Methoxyphenyl)-2-methylnicotinate (4h).
This compound was obtained in 78% yield, 2.11 g; mp 67 °C
(CDCl ): δ = 200.39 (CO), 159.14, 138.47,136.06, 134.40,
3
C
133.81, 131.06, 129.31, 129.18, 128.99, 128.12, 127.52, 127.34,
126.85, 124.94, 117.93, 29.78, 25.85.
(lit. [7] mp 68-69 °C; IR (KBr) ν
= 3070 (arom. CH), 2993
max
-1
(aliph. CH), 1712 (CO), 1590 cm (arom.C=C); MS (EI, 70 eV):
Anal. Calcd. for C
H NO (261.31): C, 82.73; H, 5.79; N,
18 15
+
1
m/z = 271 [M ]; H NMR (DMSO): δ = 1.32 (t, 3H, J = 7.5 Hz,
5.36. Found: C, 82.66; H, 5.63; N, 5.42.
H
OCH CH ), 2.76 (s, 3H, CH ), 3.81 (s, 3H, OCH ), 4.30 (q, 2H,
2
3
3
3
1-[6-(4-Chlorophenyl)-2-methylpyridin-3-yl]ethanone (4b).
This compound was obtained in 80% yield, 1.96 g; mp 109 °C;
J = 7.5 Hz, OCH CH ), 7.04 (d, 2H, J = 7.3 Hz, arom.H), 7.81
2
3
(d, 1H, J = 8.10 Hz, pyridyl H-5), 8.10 (d, 2H, J = 7.3 Hz,
arom.H), 8.16 (d, 1H, J = 8.11 Hz, pyridyl H-4).
IR (KBr) ν
= 3068 (arom. CH), 2990 (aliph. CH), 1677 (CO),
max
-1
+
1
Anal. Calcd. for C
H NO (271.30): C, 70.83; H, 6.32; N,
1600 cm (arom.C=C); MS (EI, 70 eV): m/z = 245 [M ];
H
16 17 3
5.16. Found: C, 70.86; H, 6.17; N, 4.97.
NMR (CDCl ): δ = 2.63 (s, 3H, COCH ), 2.85 (s, 3H, CH ),
3
H
3
3
7.45 (d, 2H, J = 8.0 Hz, phenyl-H), 7.63 (d, 1H, J = 8.0 Hz,
pyridyl H-5), 8.02 (d, 2H, J = 8.0 Hz, phenyl-H), 8.06 (d, 1H, J =
8.0 Hz, pyridyl H-4).
General Procedure for the Preparation of the Pyridine Derivatives 7.
A stirred suspension of acetic acid (10 ml) and ammonium
acetate (1 g), was treated with each of the enaminone 1a-d (10
mmol). The reaction mixture was heated under reflux for 1 hour
after which it was cooled to room temperature. The precipitate,
which formed, was collected by filtration and successively crys-
tallized from dioxane.
Anal. Calcd. for C
H NOCl (245.7): C, 68.43; H, 4.92; N,
14 12
5.70. Found: C, 68.38; H, 4.59; N, 5.61.
General Procedure for the Preparation of the Pyridine Derivatives
4e-h.
To a solution of each of the enaminones 1a-d (10 mmol) and
ammonium acetate (1 g) in acetic acid (10 ml), ethyl acetoacetate
(1.56 g, 12 mmol) was added. The reaction mixture was heated
under reflux for 1 hour. The solvent was evaporated under vac-
uum, and the residual solid was crystallized from dioxane.
Naphthalen-2-yl-(6-naphthalen-2-yl-pyridin-3-yl)methanone (7a).
This compound was obtained in 85% yield, 3.05 g; mp 145 °C;
-1
IR (KBr) ν
= 3055 (arom. CH), 1651 (CO), 1600 cm
max
+
1
(arom.C=C); MS (EI, 70 eV): m/z = 359 [M ]; H NMR
(DMSO): δ = 7.56-7.66 (m, 4H, arom. H), 7.97-8.17 (m, 8H,
H
arom. H), 8.33-8.82 (m, 4H, arom. H), 9.10 (s, 1H, pyridyl H-2).
Ethyl 2-Methyl-6-naphthalen-2-yl-nicotinate (4e).
Anal. Calcd. for C
3.90. Found: C, 86.67; H, 4.73; N, 4.03.
H NO (359.40): C, 86.88; H, 4.77; N,
26 17
This compound was obtained in 89% yield, 2.60 g; mp 92 °C;
IR (KBr) ν
= 3080 (arom. CH), 2924 (aliph. CH), 1715 (CO),
max
-1
+
1
(4-Chlorophenyl)-[6-(4-chlorophenyl)pyridin-3-yl]methanone (7b).
This compound was obtained in 81% yield, 2.65g; mp 191 °C
(lit. [8] mp 190 °C); IR (KBr) ν
1596 cm (arom. C=C); MS (EI, 70 eV): m/z = 291 [M ]; H
NMR (DMSO): δ = 1.46 (t, 3H, J = 7.2 Hz, OCH CH ), 2.99 (s,
H
2
3
3H, CH ), 4.44 (q, 2H, J = 7.5 Hz, OCH CH ), 7.52-7.57 (m,
3
2
3
= 3055 (arom. CH), 1600
max
2H, naphthyl-H), 7.80 (d, 2H, J = 8.16 Hz, pyridyl H-5), 7.88-
7.92 (m, 1H, naphthyl-H), 7.96-8.00 (m, 2H, naphthyl-H), 8.22
(d, 1H, J = 8.2 Hz, naphthyl-H), 8.33 (d, 1H, J = 8.2 Hz, pyridyl
H-4), 8.58 (s, 1H, naphthyl-H).
-1
+
(arom.C=C), 1640 cm (CO); MS (EI, 70 eV): m/z = 328 [M ];
1
H NMR (CDCl ): δ = 7.48 (d, 4H, J = 8.0 Hz, arom. H), 7.84
3
H
(d, 2H, J = 8.0 Hz, arom-H), 7.77 (d, 1H, J = 8.3 Hz, pyridyl H-
5), 8.02 (d, 2H, J = 8.0 Hz, arom-H), 8.24 (d, 1H, J = 8.3 Hz,
pyridyl H-4), 9.08 (s, 1H, pyridyl H-2).
Anal. Calcd. for C
H NO (291.33): C, 78.33; H, 5.88; N,
19 17 2
4.81. Found: C, 78.45; H, 5.93; N, 5.07.
Anal. Calcd. for C H NOCl (328.2): C, 65.87; H, 3.38; N,
18 11
2
4.27. Found: C, 65.72; H, 3.19; N, 4.27.
Ethyl 6-(4-Chlorophenyl)-2-methylnicotinate (4f).
This compound was obtained in 84% yield, 2.32 g; mp 76 °C;
p-Tolyl-(6-p-tolylpyridin-3-yl)methanone (7c).
This compound was obtained in 78% yield,2.23 g; mp 184 °C;
IR (KBr) ν
= 3090 (arom. CH), 2979 (aliph. CH), 1724 (CO),
max
-1
+
1
1607 cm (arom.C=C); MS (EI, 70 eV): m/z = 275 [M ];
H
IR (KBr) ν
= 3100 (arom. CH), 2916 (aliph. CH), 1643 (CO),
max
NMR (CDCl ): δ = 1.44 (t, 3H, J = 6 Hz, OCH CH ), 2.93 (s,
-1
+
1
3
H
2
3
1603 cm (arom.C=C); MS (EI, 70 eV): m/z = 287 [M ];
H
3H, CH ), 4.42 (q, 2H, J = 6 Hz, OCH CH ), 7.47 (d, 2H, J = 8.0
3
2
3
NMR (CDCl ) δ = 2.45 (s, 3H, CH ), 2.48 (s, 3H, CH ), 7.34
3
H
3
3
Hz, phenyl-H), 7.62 (d, 1H, J = 8.0 Hz, pyridyl H-5), 8.03 (d, 2H,
J = 8.0 Hz, phenyl-H), 8.29 (d, 1H, J = 8.0 Hz, pyridyl H-4).
(d, 4H, J = 8.1 Hz, arom. H), 7.79 (d, 2H, J = 8.1 Hz, arom-H),
7.87 (d, 1H, J = 8.3 Hz, pyridyl H-5), 8.01 (d, 2H, J = 8.1 Hz,
arom-H), 8.20 (d, 1H, J = 8.3 Hz, pyridyl H-4), 9.06 (s, 1H,
pyridyl H-2).
Anal. Calcd. for C
H NO Cl (275.76): C, 65.27; H, 5.07; N,
15 14 2
5.07. Found: C, 65.21; H, 4.98; N, 5.23.
Anal. Calcd. for C
4.88. Found: C, 83.67; H, 5.73; N, 5.04.
H NO (287.34): C, 83.59; H, 5.96; N,
20 17
Ethyl 2-Methyl-6-p-tolylmethylnicotinate (4g).
This compound was obtained in 82% yield, 2.09 g; mp 55 °C
(4-Methoxyphenyl)-[6-(4-methoxyphenyl)pyridin-3-yl]-
methanone (7d).
(lit. [17] mp 54 °C); IR (KBr) ν
= 3090 (arom.CH), 2989
max
-1
(aliph. CH), 1711 (CO), 1600 cm (arom.C=C); MS (EI, 70 eV):
+
1
m/z = 255 [M ]; H NMR (DMSO): δ = 1.31 (t, 3H, J = 7.5 Hz,
This compound was obtained in 75% yield, 2.39 g; mp 186 °C
H
OCH CH ), 2.34 (s, 3H, CH ), 2.76 (s, 3H, CH ), 4.29 (q, 2H,
(lit. [8] mp 188 °C); IR (KBr) ν
= 3100 (arom. CH), 2993
2
3
3
3
max

1038
B. Al-Saleh, M. M. Abdelkhalik, A. Mohammed Eltoukhy, and M. H. Elnagdi
Vol. 39
-1
Anal. Calcd. for C
C, 75.12; H, 5.02.
H O (480.52): C, 74.99; H, 5.03. Found:
30 24 6
(aliph. CH), 1607 (arom.C=C), 1675 cm (CO); MS (EI, 70 eV):
+
1
m/z = 319 [M ]; H NMR (CDCl ): δ = 3.80 (s, 3H, OCH ),
3
H
3
3.91 (s, 3H, OCH ), 7.08 (d, 4H, J = 7.8 Hz, arom. H), 7.79 (d,
3
2H, J = 7.8 Hz, arom-H), 7.83 (d, 1H, J = 8.3 Hz, pyridyl H-5),
8.10 (d, 2H, J = 7.8 Hz, arom-H), 8.25 (d, 1H, J = 8.3 Hz, pyridyl
H-4), 9.11 (s, 1H, pyridyl H-2).
REFERENCES AND NOTES
[1] B. Al-Saleh, M. M. Abdelkhalik, A. Al-Enzy and M. H.
Elnagdi, J. Chem. Res. (S) 654 (1999).
[2] C. Reidlinger, R. Dworczak and H. Junek, Monatsh.
Chem., 129, 1207 (1998).
Anal. Calcd. for C
H NO (319.36): C, 75.22; H, 5.37; N,
20 17 3
4.39. Found: C, 75.28; H, 5.12; N, 4.40.
General Procedure for the Preparation of 9a,c,d.
[3] M. Buback, J. Abeln, T. Hubsch, C. Ott and L. F. Tietze,
Liebigs Ann. Chem., 9 (1995).
Each of compound 1a,c,d (10 mmol) was refluxed in acetic
acid (20 ml) for 2 hours after which it was cooled to room
temperature. The precipitate, which formed, was collected by
filtration and successively crystallized from ethanol/dioxane
(3:1 v/v).
[4] J. G. Hardman, L. E. Limbird, P. B. Molinoff, R. W.
Ruddon and A. G. Giman, The Pharmacological Basis of Therapeutic,
Goodman and Gillman's, ninth ed, 1070 (1996).
[5] J. A. Joule, K. Mills and G. F. Smith, Heterocyclic
Chemistry, third ed., Chapman & Hall, London, UK, 56-118 (1995).
[6] A. R. Katritzky, Handbook of Heterocyclic Chemistry,
Pergamon Press, Oxford, UK, 381-411 (1985).
[7] E. Gräf and R. Troschütz, Synthesis, 1216 (1999).
[8] P. Ollinger, W. Remp, H. Junek, Monatsh. Chem., 105, 346
(1974).
1,3,5-Tri-2-naphthoylbenzene (9a).
This compound was obtained in 90% yield, 4.87 g; mp 225
-1
°C; IR (KBr) ν
= 3047 (arom. CH), 1651 (CO), 1608 cm
max
+
1
(arom. C=C); MS (EI, 70 eV): m/z = 540 [M ]; H NMR
(DMSO): δ = 7.63-7.71 (m, 6H, naphthyl-H), 8.00 (t, 6H, J =
H
8.0 Hz, naphthyl-H), 8.10 (d, 3H, J = 8.8 Hz, naphthyl-H),
8.22 (d, 3H, J = 8.8 Hz, naphthyl-H), 8.45 (s, 3H, phenyl-H),
8.59 (s, 3H, naphthyl-H).
[9] P. Lue and J. V. Greenhill, Adv. Heterocycl. Chem., 67, 207
(1997); editor A. R. Katritzky, Academic Press, New York.
[10] F. Al-Omran, N. Al-Awadi, A. A. El-Khair and M. H.
Elnagdi, Org. Prep. Proced. Int., 29, 285 (1997); S. M. Agamy, M. M.
A. Abdebkhaler, M. H. Mohamed and M. H, Elnagdi, Z. Naturforsch,
56b, 1074 (2001).
[11] S. M. Al-Mousawi, K. S. George and M. H. Elnagdi,
Pharmazie, 8, 54 (1999).
[12] E. Breitmaier, Structure Elucidation by NMR in Organic
Chemistry, A Practical Guide, John Wiley & Sons Ltd, Chichester,
UK, 27 (1993).
[13] M. M. Abdelkhalik, M. H. Elnagdi and S. M. Agamy,
Synthesis, 1166 (2000).
[14] K. M. Al-Zaydi, E. A. Hafez and M. H. Elnagdi, J. Chem.
Res. (S), 154 (2000).
[15] M. M. Abdelkhalik, S. M. Agamy and M. H. Elnagdi, Z.
Naturforsch, 55b, 1211 (2000).
Anal. Calcd. for C
H O (540.58): C, 86.65; H, 4.48. Found:
39 24 3
C, 86.43; H, 4.44.
1,3,5-Tri-p-toluoylbenzene (9c).
This compound was obtained in 90% yield, 3.88 g; mp 156
°C; IR (KBr) ν
= 3060 (arom. CH), 2956 (aliph. CH), 1645
max
-1
+
cm (CO), 1602 (arom. C=C); MS (EI, 70 eV): m/z = 432 [M ];
1
H NMR (DMSO) δ = 2.42 (s, 9H, 3 CH ), 7.20 (d, 6H, J = 8.0
H
3
Hz, arom. H), 7.82 (d, 6H, J = 8.0 Hz, arom. H), 8.45 (s, 3H,
phenyl-H).
Anal. Calcd. for C
H O (432.52): C, 83.31; H, 5.59. Found:
30 24 3
C, 83.36; H, 5.42.
1,3,5-Tri-4-methoxybenzoylbenzene (9d).
[16] B. Al-Saleh, N. Al-Awadi, H. Al-Kandari, M. M.
Abdelkhalik and M. H. Elnagdi, J. Chem. Res. (S) 16 (2000).
[17] U. P. Basu, J. Indian Chem. Soc., 12, 289 (1935).
[18] M. M. Abdelkhalik and M. H. Elnagdi, Synthetic
Communications, 32, 153 (2002).
This compound was obtained in 88% yield, 4.22 g; mp 177 °C;
-1
IR (KBr) ν
= 3054 (arom. CH), 2956 (aliph. CH), 1676 cm
max
+
1
(CO), 1609 (arom. C=C); MS (EI, 70 eV): m/z = 480 [M ]; H
NMR (DMSO): δ = 3.90 (s, 9H, 3OCH ), 7.06 (d, 6H, J = 7.8
H
3
Hz, arom. H), 8.01 (d, 6H, J = 7.8 Hz, arom. H), 8.48 (s, 3H,
phenyl-H).
[19] F. Al-Omran, .M. M. Abdelkhalik, A. Abou-Elkhair and M.
H. Elnagdi, Synthesis, 91 (1997).