Enaminones as building blocks in heterocyclic syntheses: A new approach to polyfunctionally substituted cyclohexenoazines

Article abstract of DOI:10.1002/jhet.5570400421

A variety of polyfunctionally substituted condensed pyridines and pyrazolotetrahydroquinazolines have been synthesized utilizing cyclic enaminones as starting materials.

Full text of DOI:10.1002/jhet.5570400421

Jul-Aug 2003
Enaminones as Building Blocks in Heterocyclic Syntheses: A New
Approach to Polyfunctionally Substituted Cyclohexenoazines
Saleh Al-Mousawi[a], Mervat Mohammed Abdelkhalik [b], Elizabeth John [a],
689
*
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 December 19, 2002
Received Revised June 30, 2003
A variety of polyfunctionally substituted condensed pyridines and pyrazolotetrahydroquinazolines have
been synthesized utilizing cyclic enaminones as starting materials.
J. Heterocyclic Chem., 40, 689(2003).
In conjunction to our previous interest in utilizing enam-
for this reaction product as the HMBC spectra revealed
correlation between the cyano function at d = 116.47 and
the singlet pyridyl-H in position 4 at d = 8.33 ppm. The
alternative structure 10 which could have resulted via ini-
tial condensation at the carbonyl function should display a
correlation between the pyridyl-CH and the carbonyl func-
tion in position 7, which is not observed. Structure 7 was
ruled out based on the stability of the reaction product on
reflux in ethanol/hydrochloric acid solution, a condition
that would lead to hydrolysis of the imine moiety in 7 or
rearrangement into 8.
inones as building blocks for synthesis of polyfunctionally
substituted heteroaromatics as potential agrochemicals or
intermediates in dye and pharmaceutical industries [1-6],
we report here our further results in this area. Thus enam-
inones 2a,b were synthesized via condensation of 1a,b
with dimethylformamide dimethylacetal (DMFDMA) in
refluxing xylene utilizing modified literature procedure
[
7]. The enaminones 3,4 were prepared following litera-
ture procedures [1,5,6] (Scheme1).
Scheme 1
Similarly, reacting 2a,b with cyanothioacetamide
afforded 11a,b in good yield. Structures 11a,b were estab-
lished for these reaction products based on analogy to the
well established behavior of 2a,b towards malononitrile.
Compounds 11a,b thus reacted with phenacyl bromide to
yield the thienoquinolines 13a,b probably formed via
intermediacy of 12a,b that could not be isolated. Ready
Scheme 2
The enaminones 2a,b reacted with malononitrile in
refluxing acetic acid and in presence of ammonium acetate
to yield products of condensation via dimethylamine elim-
ination. These may thus be formulated as 6-10. Thus, ini-
tial Michael addition at the activated double bond can
afford 6 that would then cyclise into 7 or isomerise into 8.
Alternatively, condensation of the carbonyl group in 2a,b
to the active methylene moiety would afford 9 that can
then cyclise into 10 (Scheme 2). The acyclic compound 6
1
3
could be ruled out based on the C NMR spectra that
3
revealed the presence of only three sp carbons at d = 50.6
and 33.32 ppm for the two CH and at d = 28.44 ppm for
2
the two equivalent CH groups. Structure 8 is established
3

6
90
S. Al-Mousaw, M. M. Abdelkhalik, E. John, M. H. Elnagdi
Vol. 40
formation of condensed thiophenes from reaction of
-thioxopyridine-3-carbonitrile is a well-established route
to pyridothiophenes that has been recently utilized by us for
synthesis of benzotriazolylthienopyridines [8] (Scheme3).
cated pyridyl H-5 and H-4 as two doublets at d = 7.68
ppm and 7.97 ppm with J = 8.2 Hz. If these were for H-3
and H-2 in 15, one would expect J of 4-6 Hz [12].
Reacting 3 with acetylacetone afforded 14b based on
observations similar to those discussed above. The reac-
tion of 3 with cyanothioacetamide has afforded the
pyridinthione 16 by similar sequence.
2
Scheme 3
The reaction of heterocyclic amines with 4a,b has been
recently utilized by us for synthesis of azolopyrimidines
[
3
11-14]. Now we have found that 2a,b also react with
-amino-1H-pyrazole 17 to yield a pyrazolo[1,5-a]quina-
zoline derivatives that may be formulated as 18-20.
Structures 20a,b were established by synthesizing them
via the reaction of 21 with 1a,b. In contrast to the behav-
ior of 2a, compound 2b reacted with 17 to yield the enam-
inone 19 that cyclized further into 20 in refluxing DMF
(
Scheme 4).
Compounds 2a,b reacted with 3-aminocoumarine 22 to
yield equilibrium mixture of enaminones 23a,b and 24a,b.
Similar reaction of 4a,b with 22 gave a mixture of the
Z-and E- enaminones 25a,b and 26a,b in relative ratio
8
5:15 for 4a and 80:20 for 4b. The predominance of Z
form for these products reflects the effect of hydrogen
bonding in stabilizing this structure (Scheme 5). Trials to
effect cyclisation of 23-26 into pyridine derivatives under
diversity of cyclisation reaction conditions failed.
The coupling reaction of 4a,b with aromatic and het-
eroaromatic diazonium salts has been extensively utilized
in recent years for synthesis of arylhydrazonopropanals
that proved to be excellent starting materials for synthesis
of polyfunctionally substituted pyridazines [6,15-17]. In
this work, trials to couple 3 with benzenediazonium chlo-
ride failed. However, p-nitrobenzene diazonium chloride
Although enaminones 4a,b have been recently reported
to react smoothly with ethyl acetoacetate and acetylace-
tone in refluxing acetic acid and in presence of ammonium
acetate [9,10], we failed to condense 2a,b in similar man-
ner with these reagents. However, enaminone 3 reacted
smoothly with both reagents to yield products that were
formulated as the pyridines 14a,b and not isomeric 15a,b
1
1
based on H NMR. Thus, H NMR spectra of 14a indi-
Scheme 4

Jul-Aug 2003
Enaminones as Building Blocks in Heterocyclic Syntheses
691
Scheme 5
coupled readily with 3 to yield arylhydrazonopropanals
that proved to exist as an equilibrium mixture of 27 and 28.
Thus, H NMR showed two formyl signals at d = 9.52 and
14.00 (br s, 1H, NH) for the anti-form 28 whereas signals
at d = 7.55-7.60 (m, 2H, coumarinyl-H), 7.67-7.80 (m,
2H, coumarinyl-H); 8.24 (d, 2H, J = 9.2 Hz, p-nitro-
phenyl-H), 8.32 (d, 2H, J = 9.2 Hz, p-nitrophenyl-H), 8.64
(s, 1H, coumarinyl H-4), 9.52 (s, 1H, CHO), 12.92 (br s,
1H, NH) revealed the syn-form 27.
1
1
0.01 ppm of relative intensity 2:1. Also, two NH signals
at d = 12.93 and 14.01 ppm of the same relative intensities
appeared. The downfield shift of formyl proton in the anti-
form is a result of hydrogen bonding with the hydrazone
The enaminone 5 also coupled with benzene diazonium
1
1
NH as indicated in structure 28. Thus the H NMR spectra
chloride to yield 29. H NMR of this reaction product indi-
revealed signals at d = 7.45-7.48 (m, 2H, coumarinyl-H),
cates that it exists solely in the iminohydrazone form.
The enaminones 2 a , bf ailed to couple with aromatic dia-
zonium salts however, compound 2 bcoupled readily with
diazotised heterocyclic amine 30 yielding a biscoupling
7
.66-7.67 (m, 2H, coumarinyl-H), 7.81 (d, 2H, J = 6.7 Hz,
p-nitrophenyl-H), 8.01 (d, 2H, J = 9.2 Hz, p-nitrophenyl-
H); 8.52 (s, 1H, coumarinyl H-4), 10.01 (s, 1H, CHO),
product of molecular formula C H N (MW = 292).
1
4 12 8
This was formulated as 3 3and is assumed to be formed v i a
initial Japp Klingman type cleavage of the dimethy-
laminomethylene moiety in 2 byielding3 1that cyclised into
Scheme 6
3
2and then coupled further with 3 0to yield a hydrazone
that cyclises into the final isolable product 3 3. This same
product was isolated on coupling 5 with 3 0(Scheme 6).
EXPERIMENTAL
All melting points are uncorrected. IR spectra were recorded in
1
KBr disks using a Shimadzu IR-740 spectrophotometer. H and
1
3
C NMR spectra were recorded on a Bruker Ac-80 spectrometer
2
with [ H ]DMSO as solvent (unless stated otherwise) and TMS
6
as internal standard; chemical shifts are reported in d units (ppm).
Mass spectra were measured on Gs/MS INCOS XL Finnigan
MAT. Microanalyses were performed on LECO CHNS-932.

6
92
S. Al-Mousaw, M. M. Abdelkhalik, E. John, M. H. Elnagdi
Vol. 40
Analytical measurements were performed in Analab in Kuwait
University, and Analytical data unit at Cairo University.
nmr (DMSO): d = 1.98-2.05 (m, 2H, CH ), 2.46 (t, 2H, J = 6.4
2
Hz, CH ), 2.86 (t, 2H, J = 6.4 Hz, CH ), 8.35 (s, 1H, H-4), 13.01
2
2
(
br s, 1H, NH).
General Procedure for the Preparation of Compounds2a,b and 3.
Anal. Calcd. for C H N O (188.18): C, 63.82; H, 4.29; N,
1
0 8 2 2
A suspension of each of cyclohexane-1,3-dione 1a, 5,5-
dimethylcyclohexane-1,3-dione 1b (10 mmol) and 3-acetyl-
benzo[b]pyran-2-one (10 mmol) was treated with N,N-dimethyl-
formamide dimethylacetal (1.46 g, 11 mmol) in xylene (20 ml).
The reaction mixture was heated under reflux for 3 to 5 h. The
solid product obtained upon cooling was recrystallized from the
proper solvent.
14.89. Found C, 63.95; H, 4.37; N, 14.90.
7
,7-Dimethyl-2,5-dioxo-1,2,5,6,7,8-hexahydroquinoline-3-car-
bonitrile (8b).
Compound 8b was obtained as white crystals in 75 % yield
(1.62 g); mp: 327° ; ir (KBr) n
= 2953 (NH), 2230 (CN),
max
-
1
+
1
1668 cm (CO). MS (EI, 70 EV): m/z = 216 [M ]. H nmr
DMSO): d = 1.03 (s, 6H, 2 CH ), 2.40 (s, 2H, CH ), 2.80 (s, 2H,
(
3
2
2
-Dimethylaminomethylenecyclohexan-1,3-dione (2a).
CH ), 8.33 (s, 1H, H-4), 12.95 (br s, 1H, NH).
2
Compound 2a was obtained as brown crystals in 60 % yield
Anal. Calcd. for C H N O (216.23): C, 66.65; H, 5.59; N,
12 12 2 2
(
(
[
1.0 g) from (CHCl /pet.ether); mp: 116°, Lit. mp. 114° [7] ; ir
12.96. Found C, 66.48; H, 5.55; N, 13.09.
3
-
1
KBr) n
= 1656 cm (CO). MS (EI, 70 EV): m/z = 167
max
General Procedure for the Preparation of Compounds 11a,b.
+
1
M ]. H nmr (DMSO): d = 1.77-1.80 (m, 2H, CH ), 2.29 (t, 4H,
2
J = 6.4 Hz, 2 CH ), 3.02 (s, 3H, NCH ), 3.39 (s, 3H, NCH ),
A mixture of each of compound 2a,b (1.67 g, 10 mmol) and
cyanothioacetamide (1 g, 10 mmol) in ethanol 20 ml in the pres-
ence of few drops of triethylamine, was refluxed for 20 min. The
solution was poured onto water containing drops of concentrated
hydrochloric acid to deposit a solid that was collected by filtra-
tion and crystallized from proper solvent.
2
3
3
7
.99 (s, 1H, CH).
2
-Dimethylaminomethylene-5,5-dimethylcyclohexan-1,3-dione 2 b.
Compound 2b was obtained as yellow crystals in 70 % yield
(
(
1.36 g) from (CHCl / pet.ether) mp:
3
9
4 °, Lit. mp 94 °[7]. ir (KBr) n
= 1663 cm-1 (CO); MS
max
5
-Oxo-2-thioxo-1,2,5,6,7,8-hexahydroquinoline-3-carbonitrile
+
1
EI, 70 EV): m/z = 195 [M ]. H nmr (DMSO) d = 0.96 (s, 6H,
CH ), 2.21 (s, 4H, 2 CH ), 3.04 (s, 3H, NCH ), 3.38 (s, 3H,
(
11a).
2
3
2
3
NCH ), 7.95 (s, 1H, CH).
Compound 11a was obtained in 57 % yield (1.16 g) from
ethanol/DMF; mp >350°; ir (KBr) n = 2955 (NH), 2229
3
max
3
-(3-Dimethylaminopropenoylcoumarine) (3).
Compound3 was obtained as yellow crystals in 60 % yield (1.45
-
1
+
1
(
CN), 1663 cm (CO). MS (EI, 70 EV): m/z = 204 [M ]. H
nmr (DMSO): d = 2.01-2.07 (m, 2H, CH ), 2.52 (t, 2H, J = 6.4
2
-
1
g) from ethanol; mp: 160°; ir (KBr) n
= 1717 and 1680 cm
Hz, CH ), 2.95 (t, 2H, J = 6.4 Hz, CH ), 8.31 (s, 1H, H-4), 14.36
m a x
2
2
+
1
(
CO). MS (EI, 70 EV): m/z = 243 [M ]. H nmr (DMSO): d =
(br s, 1H, NH).
2
.99 (s, 3H, NCH ), 3.19 (s, 3H, NCH ), 6.31 (d, 1H, J = 12 Hz,
Anal. Calcd for C H N OS (204.18): C, 58.82; H, 3.95; N,
3
3
10 8 2
vinyl 2-H), 7.28-7.37 (m, 2H, arom. H), 7.56-7.65 (m, 2H, arom.
H), 7.94 (d, 1H, J = 12 Hz, vinyl 3-H), 8.61 (s, 1H, pyran 4-H).
13.72, S 15.68. Found C, 58.51; H, 3.67; N, 13.30; S, 15.34.
,7-Dimethyl-5-oxo-2-thioxo-1,2,5,6,7,8-hexahydroquinoline-3-
7
Anal. Calcd. for C H NO (243.25): C, 69.12; H, 5.39; N,
1
4
13
3
carbonitrile (11b).
5
3
.76. Found C, 69.33; H, 5.39; N, 5.69.
Compound 11b was obtained in 83 % yield (1.92 g) from
-amino-5,5-dimethylcyclohex-2-enone (5).
ethanol/dioxane; mp >350°; ir (KBr) n
= 3007 (NH),
max
-
1
+
A mixture of 5,5-dimethylcyclohexane-1,3-dione 1b (1.4 g, 10
2229(CN), 1670 cm (CO). MS (EI, 70 EV): m/z = 232 [M ].
1
mmol), ammonium acetate (0.77 g, 10 mmol), acetic acid (0.6
ml, 10 mmol) was refluxed in toluene (20 ml) using Dean Stark
apparatus for 5 to 6 h. The solvent was evaporated in vacuum,
and the residual solid was crystallized from acetonitrile.
Compound 5 was obtained as yellow crystals in 65 % yield (0.9
H nmr (DMSO): d = 1.03 (s, 6H, 2 CH ), 2.44 (s, 2H, CH ),
3 2
2.91 (s, 2H, CH ), 8.24 (s, 1H, H-4), 14.41 (br s, 1H, NH).
2
Anal. Calcd for C H N OS (232.23): C, 62.06; H, 5.21; N,
12 12 2
12.06, S 13.79. Found C, 61.92; H, 5.07; N, 11.83; S, 13.00.
General Procedure for the Preparation of Compounds 13a,b.
-
1
g); mp: 167 °; ir (KBr) nmax = 2953 and 2890 (NH ), 1684 cm
(
2
+
1
A mixture of each of compound 11a,b (10 mmol) was refluxed
with bromoacetophenone (1.99 g. 10 mmol) in DMF (10 ml) for
30 min. The solid formed was collected by filtration and crystal-
lized from ethanol.
CO). MS (EI, 70 EV): m/z = 139 [M ]. H nmr (DMSO): d =
0
1
.96 (s, 6H, 2 CH ), 1.90 (s, 2H, CH ), 2.12 (s, 2H, CH ), 4.91 (s,
3 2 2
H, olefenic-H), 6.84 (br s, 2H, NH2).
Anal. Calcd. for C H NO (139.19): C, 69.03; H, 9.41; N,
8
13
1
0.06. Found C, 69.29; H, 9.24; N, 10.21.
3
-Amino-2-benzoyl-7,8-dihydro-6H-thieno[2,3-b]quinolin-5-
General Procedure for the Preparation of Compound 8a,b.
A suspension of 2a,b (1.67 g, 10 mmol), malononitrile (0.66 g,
one (13a).
Compound 13a was obtained in 59 % yield (1.89 g) from chlo-
roform; mp = 266°; ir: 1685 and 1646 (CO), 3420 cm (NH2).
MS (EI, 70 EV): m/z = 322 [M ]. H nmr (DMSO): d = 2.06 (t,
2H, J = 6.4 Hz, CH2), 2.54 (m, 2H, CH2), 2.92 (t, 2H, J = 6.4
-1
1
0 mmol) and ammonium acetate (0.77 g, 10 mmol) was
+
1
refluxed in acetonitrile (10 ml) for 2 h. The solvent was reduced
to deposit a solid that was crystallized from acetonitrile.
Hz, CH ), 7.37-7.39 (m, 1H, arom-H), 7.46-7.50 (m, 2H, arom-
2
2
,5-Dioxo-1,2,5,6,7,8-hexahydroquinoline-3-carbonitrile (8a).
Compound 8a was obtained as brown crystals in 70 % yield
H), 8.04-8.06 (m, 2H, arom-H), 8.14 (s, 2H, NH D O exchange-
able), 8.91 (s, 1H, H-4).
Anal. Calcd for C18H N O S (322.31): C, 67.07; H, 4.38; N,
2
2
(
1
1.31 g); mp: 305°; ir (KBr) n
686 and 1656 cm (CO). MS (EI, 70 EV): m/z = 188 [M ].
= 2952 (NH), 2230 (CN),
max
14 2 2
-
1
+
1
H
8.69, S 9.937. Found C, 66.71; H, 4.457; N, 8.98; S, 9.72.

Jul-Aug 2003
Enaminones as Building Blocks in Heterocyclic Syntheses
693
3
-Amino-2-benzoyl-7,7-dimethyl-7,8-dihydro-6H-thieno[2,3-b]-
General Procedure for the Preparation of Compounds 19 and 20.
quinolin-5-one (13b).
To a suspension of 2a,b (1.67 g, 10 mmol) in pyridine (10 ml),
3- aminopyrazole 17 (0.83 g, 10 mmol) was added and the reac-
tion mixture was refluxed for 10 min. The solid formed was col-
lected by filtration and crystallized in ethanol
Compound 13b was obtained in 50 % yield (1.75 g); mp =
-
1
2
33°; ir: 1674 and 1646 (CO), 3396 cm (NH ). MS (EI, 70 EV):
2
+
1
m/z = 350 [M ]. H nmr (DMSO): d = 1.04 (s, 6H, CH ), 2.62
3
(
7
s, 2H, CH ), 3.09 (s, 2H, CH ), 7.52-7.59 (m, 3H, arom-H),
.75-7.77 (m, 2H, arom-H), 8.60 (s, 2H, NH D O exchange-
2 2
2 2
5
,5-Dimethyl-2-[(1H-pyrazol-3-ylamino)-methylene]-cyclo-
hexane-1,3-dione (19).
able), 9.18 (s, 1H, H-4).
Anal. Calcd for C20H N O S (350.36): C, 68.56; H, 5.18; N,
Compound 19 was obtained in 71 % yield (1.65 g); mp 183°;
18
2 2
-
1
8
.00; S, 9.142. Found C, 68.12; H, 5.023; N, 8.39; S, 9.51.
General Procedure for the Preparation of Compounds 14a,b and
6.
To a stirred suspension of compound 3 (2.43 g, 10 mmol) and
ammonium acetate (1 g), acetic acid (10 ml), each of acetylace-
tone (1.0 g, 10 mmol) and ethyl acetoacetate (1.3 g, 10 mmol)
was added. The reaction mixtures were heated under reflux for 30
min, and then allowed to cool to room temperature. The solid
products so obtained were collected by filtration, and crystallized
from ethanol / dioxane.
ir: 2952 and 2869 (2 NH), 1668 cm (CO). MS (EI, 70 EV): m/z
+
1
=
233 [M ]. H nmr (DMSO):d = 1.00 (s, 6H, CH ), 2.33 (s, 2H,
3
CH ), 2.41 (s, 2H, CH ), 6.47 (d, 1H, J = 2.0 Hz, pyrazolyl H-4),
2
2
1
7
.76 (d, 1H, J = 2.0 Hz, pyrazolyl H-5), 8.53 (d, 1H, J = 12 Hz,
CH), 12.53 (d, 1H, J = 16 Hz, NH), 12.80 (br s, 1H, NH).
Anal. Calcd. for C H N O (233.26): C, 61.78; H, 6.48; N,
12 15 3 2
18.02. Found C, 62.10; H, 6.67; N, 18.32.
General Procedure for the Preparation of Compounds 20a,b.
A suspension each of cyclohexane and 5,5-dimethylcyclo-
hexane-1,3-dione (1.12 g, 10 mmol), in acetic acid (10 ml) was
refluxed with enaminone of 3- aminopyrazole (1.38 g, 10 mmol)
for 1.5 h. The solid formed was collected by filtration and crys-
tallized in ethanol.
Ethyl 2-methyl-6-(coumarin-3-yl)nicotinic acid ester (14a).
Compound 14a was obtained in 69 % yield (2.10 g); mp.164°;
-
1
+
ir: 1727 and 1677 cm (CO). MS (EI, 70 EV): m/z = 309 [M ].
8
,9-Dihydro-7H-pyrazolo[1,5-a]quinazolin-6-one (20a).
1
H nmr (DMSO) d = 1.35 (t, 3H, J = 7.08 Hz, OCH CH ), 2.81
2
3
(
(
1
1
s, 3H, CH ), 4.34 (q, 2H, J = 7.08 Hz, OCH CH ), 7.40-7.48
m, 2H, coumarinyl-H), 7.68 (d, 1H, J = 8.2 Hz, H-5), 7.97 (d,
H, J = 8.2 Hz, H-4), 8.24-8.29 (m, 2H, coumarinyl-H), 8.94 (s,
H, coumarinyl H-4).
Compound 20a was obtained as yellow crystals from ethanol
3
2
3
-
1
in 50 % yield (0.93 g); mp = 182°; ir: 1676 cm (CO). MS (EI,
+
1
70 EV): m/z = 187 [M ]. H nmr (CDCl ): d = 2.35-2.41 (m,
3
2H, CH ), 2.74-2.77 (t, 2H, J = 6.4 Hz, CH ), 3.50-3.54 (t, 2H,
2 2
Anal. Calcd for C H NO (309.31): C, 69.89; H, 4.89; N,
J = 6.4 Hz, CH ), 6.82 (d, 1H, J = 2.16 Hz, pyrazolyl H-4), 8.29
1
8
15
4
2
4
3
.53. Found C, 69.91; H, 4.93; N, 4.34.
(d, 1H, J = 2.16 Hz, pyrazolyl H-5), 9.03 (s, 1H, quinazolinyl H-
5
).
-(5-Acetyl-6-methylpyridin-2-yl)coumarin (14b).
Compound 14b was obtained in 75 % yield (2.10 g); mp. 207°;
Anal. Calcd. for C H N O (187.20): C, 64.16; H, 4.85; N,
10 9 3
22.45. Found C, 64.52; H, 4.85; N, 22.437.
-
1
+
ir: 1727 and 1681 cm (CO). MS (EI, 70 EV): m/z = 279 [M ].
1
8,8-Dimethyl-8,9-dihydro-7H-pyrazolo[1,5-a]quinazolin-6-one
H nmr (DMSO): d = 2.50 (s, 3H, COCH ), 2.73 (s, 3H, CH ),
3
3
(
20b).
7
.37-7.44 (m, 2H, coumarinyl H), 7.64-7.68 (m, 1H, coumarinyl
H), 7.93 (d, 1H, J = 8.5 Hz, coumarinyl H), 8.22 (d, 1H, J = 8.24
Hz, pyridyl H-3), 8.29 (d, 1H, J = 8.25 Hz, pyridyl H-4), 8.87 (s,
Compound 20b was obtained as yellow crystals from ethanol
in 50 % yield (1.07 g); mp = 142°; ir: 1679 cm-1 (CO). MS (EI,
1
H, coumarinyl H-4).
Anal. Calcd for C H NO (279.28): C, 73.11; H, 4.69; N,
70 EV): m/z = 215 [M+]. 1H nmr (DMSO): d = 1.14 (s, 6H,
1
7
13
3
CH ), 2.50 (s, 2H, CH ), 2.59 (s, 2H, CH ), 6.91 (d, 1H, J = 2.16
3
2
2
5
6
.02. Found C, 73.41; H, 4.70; N, 4.82.
Hz, pyrazolyl H-4), 8.46 (d, 1H, J = 2.16 Hz, pyrazolyl H-5),
8
1
.84 (s, 1H, quinazolinyl H-5).
Anal. Calcd. for C H N O (215.25): C, 66.95; H, 6.09; N,
9.52. Found C, 66.161; H, 6.029; N, 19.46.
-(Coumarin-3-yl)-2-thioxo-1,2-dihydropyridine-3-carbonitrile
12 13 3
(
16).
To a stirred suspension of compound 3 (2.43 g, 10 mmol) and
ammonium acetate (1 g), acetic acid (10 ml), cyanothioacetamide
1.0 g, 10 mmol) was added. The reaction mixture was heated
General Procedure for the Preparation of Compounds 23-24a,b.
(
A mixture of aminocoumarine 22 (1.61 g, 10 mmol) and 2a,b
(1.67 g, 10 mmol) was refluxed in acetic acid for 1 h. The solu-
tion was allowed to cool and the solid obtained was crystallized
in ethanol/dioxane.
under reflux for 15 min, and then allowed to cool to room tem-
perature. The solid product so obtained were collected by filtra-
tion, and crystallized from ethanol/dioxane. Compound 16 was
obtained in 68 % yield (1.9 g); mp = 298°; ir: 3103 (NH), 2225
2
2
-[(Coumarin-3-ylamino)-methylene]cyclohexane-1,3-dione 23-
4a.
-
1
+
1
(
CN), 1704 cm (CO). MS (EI, 70 EV): m/z = 280 [M ]. H
nmr (DMSO): d = 7.22 (d, 1H, J = 7.70 Hz, coumarinyl H-8),
.47 (t, 1H, J = 7.70 Hz, coumarinyl H-6), 7.52 (d, 1H, J = 8.28
Hz, pyridyl H-5), 7.77 (t, 1H, J = 7.70 Hz, coumarinyl H-7), 7.84
d, 1H, J = 8.10 Hz, pyridyl H-4), 8.23 (d, 1H, J = 7.80 Hz,
7
Compounds 23,24a were obtained as yellow crystals in 35 %
-
1
yield (1.03 g); mp = 202°; ir: 2968 (NH), 1725 and 1666 cm
+
1
(
(CO). MS (EI, 70 EV): m/z = 283 [M ]. H nmr (DMSO): d =
1.90-1.96 (m, 2H, CH ), 2.48 (t, 4H, J = 6.4 Hz, 2 CH ), 7.41 (t,
coumarinyl H-5), 8.64 (s, 1H, coumarinyl H-4), 14.10 (br s, 1H,
NH).
2
2
1H, J = 7.68 Hz, coumarinyl H-6), 7.47 (d, 1H, J = 7.68 Hz,
coumarinyl H-8), 7.58 (t, 1H, J = 7.68 Hz, coumarinyl H-7),
7.73 (d, 1H, J = 7.80 Hz, coumarinyl H-5), 8.42 (s, 1H,
Anal. Calcd for C H N O S (280.23): C, 64.29; H, 2.88; N,
1
5 8 2 2
1
0.00; S, 11.44. Found C, 64.14; H, 3.07; N, 10.27; S, 11.32.

6
94
S. Al-Mousaw, M. M. Abdelkhalik, E. John, M. H. Elnagdi
Vol. 40
coumarinyl H-4), 8.60 (d, 1H, J = 12.8 Hz, methylene-H), 12.64
coumarinyl-H), 7.81 (d, 2 (1/3)H, J = 6.7 Hz, p-nitrophenyl-H),
8.01 (d, 2 (1/3)H, J = 9.2 Hz, p-nitrophenyl-H), 8.24 (d, 2
(2/3)H, J = 9.2 Hz, p-nitrophenyl-H); 8.32 (d, 2 (2/3)H, J = 9.2
Hz, p-nitrophenyl-H); 8.52 (s, 1 (1/3)H, coumarinyl H-4); 8.64
(
br s, 1H, NH).
Anal. Calcd for C H NO (283.27): C, 67.84; H, 4.63; N,
1
6
13
4
4
.95. Found C, 67.23; H, 4.6; N, 5.057.
(
1
s, 1 (2/3)H, coumarinyl H-4), 9.52 (s, 1 (2/3)H, CHO), 10.01 (s,
(1/3)H, CHO), 12.92 (br s, 1 (2/3)H, NH); 14.00 (br s, 1 (1/3)H,
NH).
Anal. Calcd for C H N O (365.29): C, 59.18; H, 3.04; N,
5
1
,5-Dimethyl-2-[(coumarin-3-ylamino)-methylene]cyclohexane-
,3-dione (24b).
Compound 24b was obtained as yellow crystals in 75 % yield
18 11 3 6
-
1
(
2.33 g); mp = 256°; ir 2954 (NH), 1708 and 1668 cm (CO).
11.5. Found C, 59.50; H, 3.35; N, 11.66.
+
1
MS (EI, 70 EV): m/z = 311 [M ]. H nmr (DMSO): d = 1.01
Amino-5,5-dimethyl-2-(phenylhydrazono)-cyclohex-3-enone
(
(
s, 6H, 2 CH ), 2.08 (s, 2H, CH ), 2.41 (s, 2H, CH ), 7.41 (t,
3 2 2
H, J = 7.68 Hz, coumarinyl H-6), 7.46 (d, 1H, J = 7.68 Hz,
29).
1
coumarinyl H-8), 7.58 (t, 1H, J = 7.68 Hz, coumarinyl H-7),
.73 (d, 1H, J = 7.80 Hz, coumarinyl H-5), 8.40 (s, 1H,
coumarinyl H-4), 8.60 (d, 1H, J = 12.8 Hz, methylene-H),
Compound 5 (10 mmol) was dissolved in ethanol (20 ml) and
7
treated with sodium acetate (1.23 g, 15 mmol), then gradually
treated under stirring with a solution of benzenediazonium chlo-
ride prepared from aniline and (10 mmol) and the appropriate
quantities of both hydrochloric acid and sodium nitrite. The solid
product, so formed, was collected by filtration and crystallized
from ethanol. Compound 29 was obtained in 80 % yield (1.94 g);
1
2.00 (br s, 1H, NH).
Anal. Calcd for C H NO (311.32): C, 69.44; H, 5.50; N,
1
8
17
4
4
.50. Found C, 69.50; H, 5.35; N, 4.64.
General Procedure for the Preparation of Compounds 25 a,b.
A mixture of aminocoumarine 22 (1.61g, 10 mmol) and 4a,b
-
1
mp = 226°; ir: 3151 and 3026 (NH ), 2953 (NH), 1620 cm
2
(CO). MS (EI, 70 EV): m/z = 243 [M+]. 1H nmr (DMSO): d =
(
10 mmol) was refluxed in pyridine for 4 hrs. The solution was
1.04 (s, 6H, 2CH ), 2.33 (s, 2H, CH ), 2.62 (s, 2H, CH ), 7.29-
3
2
2
allowed to cool and the solid obtained was crystallized in
ethanol/dioxane.
7.33 (m, 1H, arom-H), 7.43-7.47 (m, 2H, arom-H), 7.68 (m, 2H,
arom-H), 8.95 (br s, 1H, NH), 11.42 (br s, 1H, NH).
Anal. Calcd. for C H N O (243.30): C, 69.11; H, 7.04; N,
7.27. Found C, 69.12; H, 6.97; N, 17.21.
3
-(3-Oxo-3-phenylpropenylamino)coumarine (25a).
14 17 3
1
Compound 25a was obtained in 70 % yield (2.03 g) as yellow
-
1
3H-6,6-Dimethyldipyrazolo[5,1-c:5',1'-c']benzo[1,2-e:4,3-e']di-
1,2,4-triazine (33).
crystals; mp = 243°; ir: 2963 (NH), 1715 and 1638 cm (CO).
MS (EI, 70 EV): m/z = 291 [M ]. H nmr (DMSO): d = 6.40 (d,
+
1
0
2
.85 H, J = 8 Hz, H-2 in E form), 6.95 (d, 0.15H, J = 16 Hz, H-
in Z form), 7.34-7.87 (m, 9H, arom-H), 7.98 (s, 1H, coumarinyl
Each of compound 2b, 5 (10 mmol) was dissolved in ethanol
(20 ml) and treated with sodium acetate (1.23 g, 15 mmol), then
gradually treated under stirring with a solution of pyrazolyldiazo-
nium chloride (prepared from 3-aminopyrazol (10 mmol) and the
appropriate quantities of both hydrochloric acid and sodium
nitrite as has been described earlier ref.) The solid formed was
collected by filtration and crystallized from ethanol/dioxane.
Compound 33 was obtained in 80 % yield (2.33 g); mp >350°; ir:
H-4), 8.02 (d, 0.85 H, J = 8 Hz, H-1 in E form), 8.09 (d, 0.15H,
J = 16 Hz, H-1 in Z form), 11.95 (d, 1H, J = 12.4 Hz, NH).
Anal. Calcd for C18H NO (291.29): C, 74.21; H, 4.5; N,
13
3
4
3
.81. Found C, 74.13; H, 4.427; N, 4.861.
-(3-Oxo-3-thien-2-yl-propenylamino)coumarine (25b).
Compound 25b was obtained in 30 % yield (0.89 g) as yellow
-1
+
1
3
207 cm (NH). MS (EI, 70 EV): m/z = 292 [M ].
H nmr
-
1
crystals; mp = 254°; ir: 2967 (NH), 1712 cm (CO). MS (EI, 70
EV): m/z = 297 [M ]. H nmr (DMSO): d = 6.30 (d, 0.85 H, J =
8
7
(
DMSO): d = 1.71 (s, 6H, 2CH ), 5.83 (s, 1H, CH), 5.97 (d, 1H,
3
+
1
J = 1.92 Hz, pyrazolyl-H), 7.45 (d, 1H, J = 2.54 Hz, pyrazolyl-
H), 7.72 (d, 1H, J = 1.9 Hz, pyrazolyl-H), 8.52 (d, 1H, J = 2.54
Hz, pyrazolyl-H), 10.50 (s, 1H, NH).
Hz, H-2 in E form), 6.84 (d, 0.15H, J = 16 Hz, H-2 in Z form),
.22-7.85 (m, 7H, arom-H), 7.93 (s, 1H, coumarinyl H-4), 7.98
(
d, 0.85H, J = 8 Hz, H-1 in E form), 8.01(d, 0.15H, J = 16 Hz,
H-1 in Z form), 11.64 (d, 1H, J = 12.5 Hz, NH).
Anal. Calcd for C H NO S (297.26): C, 64.64; H, 3.73; N,
Anal. Calcd. For C H N (292.30): C, 57.52; H, 4.14; N,
1
4 12 8
3
8.34. Found C, 57.40; H, 4.22; N, 37.76.
1
6
11
3
Acknowledgement.
4
.71; S, 10.774. Found C, 64.67; H, 3.785; N, 4.835; S, 10.68.
The authors are grateful to University of Kuwait R. A. for
financial support through project Sc 05-00. Analytical facilities
provided by SAF are highly appreciated.
2
-[(4-Nitrophenyl)-hydrazono]-3-oxo-3-(coumarin-3-yl)-propi-
onaldehyde (27).
Compound 3 (10 mmol) was dissolved in ethanol (20 ml) and
treated with sodium acetate (1.23 g, 15 mmol), then gradually
treated under stirring with a solution of p-nitrobenzenediazonium
chloride prepared from p-nitroaniline and (10 mmol) and the
appropriate quantities of both hydrochloric acid and sodium
nitrite. The solid product, so formed, was collected by filtration
and crystallized from ethanol/dioxane. Compound 27 was
obtained in 45 % yield (1.65 g) as red crystals; mp = 209°; ir:
REFERENCES AND NOTES
[
1] F. M. El-Taweel and M. H. Elnagdi, J. Heterocyclic Chem.,
8, 981 (2001).
2] S. M. Al-Mousawi, M. A. Mohammed and M. H. Elnagdi, J.
HetrocyclicChem., 38, 989 (2001).
3] B. Al-Saleh, N. Al-Awadi, H-Al-Kandari, M. M. Abdelkhalik
and M. H. Elnagdi. J. Chem. Res. (s),16 (2000); ibid (M) 201 (2000).
4] A. Al-Etaibi, N. Al-Awadi; F. Al-Omran, M. M. Abdelkhalik
3
[
[
-
1
3
3
086 (NH), 1724 and 1685 cm (CO). MS (EI, 70 EV): m/z =
65 [M ]. 1H nmr (DMSO): d = 7.45-7.48 (m, 2 (1/3)H,
+
[
coumarinyl-H), 7.55-7.60 (m, 2 (2/3)H, coumarinyl-H), 7.66-
.67 (m, 2 (1/3)H, coumarinyl-H), 7.67-7.80 (m, 2 (2/3)H,
and M. H. Elnagdi. J. Chem. Res. (s),4 (1999); ibid (M) 151 (1999).
7
[5] F. Al-Omran, N. Al-Awadi, M. M. Abdelkhalik, K. Kaul, A.

Jul-Aug 2003
Enaminones as Building Blocks in Heterocyclic Syntheses
695
A. El-Khair and M. H. Elnagdi. J. Chem. Res. (s), 84 (1997); ibid (M) 308
1997).
6] F. Al-Omran, M. M. Abdelkhalik, A. A. El- Khair and M. H.
Elnagdi Synthesis, 91 (1997).
7] B. Al-Saleh, M. M. Abdelkhalik, A. Eltokhy and M. H.
Elnagdi. J. Heterocyclic Chem.,39, 1035(2002).
8] B. Al-Saleh, M. M. Abdelkhalik, M. A. El-Apasery and M. H.
Elnagdi J. Heterocyclic Chem.,40, 171,(2003).
9] M. M. Abdelkhalik, S. M. Agamy and M. H. Elnagdi, Z.
Naturforsch, 55, 1211 (2000).
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Res. (s),154 (2000); ibid (M) 510 (2000).
11] A. Al-Enzy, B. Al-Saleh and M. H. Elnagdi, J. Chem. Res. (s),
4 (1997); ibid (M) 110 (1997).
(
[12] S. Al-Moussawi, K. Kaul, M. A. Mohammed and M. H.
Elnagdi, J. Chem. Res. (s),318 (1997); ibid (M) 2026 (1997).
[13] B. Al-Saleh, M. M. Abdelkhalik, A. Al-Enzy, and M. H.
Elnagdi, J. Chem. Res. (s),648 (1999); ibid (M) 2801 (1999).
[14] B. Al-Saleh, N Al-Awadi, H. Alkandari, M. M. Abdelkhalik
and M. H. Elnagdi, J. Chem. Res. (s),16 (1997); ibid (M) 201 (2000).
[15] M. M. Abdelkhalik, S. M. Agamya and M. H. Elnagdi
Synthesis,861 (2001).
[16] F. Al-Omran, M. M. Abdelkhalik, A. Abou- Elkhair and M. H.
Elnagdi. Synthesis,91 (1997).
[17] N. Al-Awadi, M. H. Elnagdi, Y. A. Ibrahim, K. Kaul and A.
Kumar, Tetrahedron, 57, 1609, (2001).
[
[
[
[
[
[