Studies with Enaminones: The reaction of enaminones with Aminoheterocycles. A route to Azolopyrimidines, Azolopyridines and Quinolines

Article abstract of DOI:10.1002/jhet.5570410219

The enaminones 1b,d,f react with 4-phenyl-3-methyl-5-pyrazoleamine 3a to yield the pyrazole derivatives 4a-c that cyclised readily on reflux in pyridine solution in presence of hydrochloric acid to yield the pyrazolo[1,5-a]pyrimidines 5a-c. Similarly 3(5)

Full text of DOI:10.1002/jhet.5570410219

Mar-Apr 2004
267
Studies with Enaminones: The reaction of enaminones with
Aminoheterocycles. A route to Azolopyrimidines, Azolopyridines and
Quinolines
Sarah Almazroaa, Mohamed H. Elnagdib and Abdellatif M. Salah El-Din*b
a
Department of Chemistry, Girl's College of Education, Ryad,
Kingdom of Saudi Arabia
Department of Chemistry; Faculty of Science; Cairo University ,Giza-A. R. Egypt
b
e-mail: shelmy@access.com.eg
Received December 18, 2002
Received Revised October 18, 2003
The enaminones 1b,d,f react with 4-phenyl-3-methyl-5-pyrazoleamine 3a to yield the pyrazole deriva-
tives 4a-c that cyclised readily on reflux in pyridine solution in presence of hydrochloric acid to yield the
pyrazolo[1,5-a]pyrimidines 5a-c. Similarly 3(5)-amino-1H-triazole (3b) reacted with 1b,d,f to yield the tri-
azolo[1,5-a]pyrimidines 5d-f. In contrast attempted condensation of the 5-tetrazoloamine (3c) with 1a,d,e
resulted in its trimerisation and only triaroylbenzene 8a,d,e was isolated. The reaction of 1a,b,d with
anthranilonitrile 9a and the reaction of 1a-c with the 2-aminocyclohexene thiophene-3-nitrile 10a afforded
the cis enaminones 11a-c and 12a-c. Similarly, reaction of 1a-c with the methylanthranilate 9b and reaction
of 1b,e with ethyl 2-aminocyclohexene thiophene-3-carboxylate 10b afforded the cis enaminones 11d-f and
12d,e respectively. Attempted cyclization of 11a-c into quinoline failed. Successful cyclization of 11d into
the quinolinone 13 could be affected, on heating for five minutes in a domestic microwave oven at full
power. The reaction of 1a-c,f with piperidine afforded the trans enaminones 14a-d. Similarly, trans 14e was
formed from the reaction of 1b with morpholine. The coupling reaction of 1b with excess of benzene diazo-
nium chloride afforded the formazane 16. The enaminone 2 reacted with heterocyclic amines to yield the
pyridones 17,18.
J. Heterocyclic Chem., 41, 267 (2004).
Scheme 1
In conjunction to our interest in the chemistry of enam-
inones [1-3], we report here our results aiming to further
explore synthetic potential of this class of compounds. The
newly required enaminones 1a-f and 2 were prepared via
refluxing methyl ketones and dibenzylketone with excess of
dimethylformamide dimethylacetal (DMFDMA). Attempted
preparation of 1b,c by refluxing the respective methyl
ketones with DMFDMA in refluxing acetic acid [4] or in
toluene solution [5] utilizing reported procedure for synthesis
of enaminones from reaction of arylmethyl ketones with
DMFDMA resulted in less than 25% yield even after pro-
longed reflux. The enaminones 1b,d,f reacted with the
aminopyrazole derivative 3a to yield the enaminone 4a-c.
The structures of which proved to exist in the c i s form as 1H
NMR revealed the presence of olifinic protons at δ 5.95 and
6.85 ppm with J = 9 Hz typical for cis olefinic protons.
We believe that domination the cis form is a result of
hydrogen bonding of the NH and aroylcarbonyl which
"fixes" this form. Compounds 4a-c readily cyclized into
the pyrazolo[1,5-a]pyrimidines 5a-c on reflux in pyridine
solution in the presence of concentrated hydrochloric acid
(cf. Scheme 1).
4,5
X
Y
R
4,5
X
Y
R
a
b
c
C-Ph C-Me 4-ClC H
d
e
f
N
N
N
CH
CH
CH
4-ClC H
Thienyl
4-CH C H
3 6 4
6
4
6
4
C-Ph C-Me Thienyl
C-Ph C-Me 4-CH C H
3
6
4
In contrast to this attempted consideration of 5-tetrazole
amine 3c with 1a,d,f failed, only the triaroyl benzenes
8a,d,f were isolated. We believe that acidity of the reaction
mixture has prompted such trimerization which has very
recently been reported to occur on refluxing enaminones in
acetic acid solution. Formation of intermediates 6 and 7 is
suggested although direct concerted 2+2+2 cycloaddition
leading directly to 7 cannot be overlooked (cf. Scheme 2).
The reaction of pyrazole amines with enaminones has
been reported earlier, however to our knowledge this is the
first reported isolation of 4 thus confirming structure of the
formed pyrazolo[1,5-a]pyrimidines. Similar to the
reported behavior of 1,2,4-1H-triazolo-5-amine (3b)
toward enaminones, 3b reacted with 1b,d,f to yield the
1,2,4-triazolo[1,5-a]pyrimidines 5d-f, respectively.

268
S. Almazroa, M. H. Elnagdi and A. M. Salah El-Din
Vol. 41
Trimerization of enaminones into triazoylbenezenes has
recently been reported from our laboratories [6,7].
microwave oven at full power. The reaction of 1a,c,f with
piperidine afforded the t r a n s enaminones 1 4 a , c , f .
Scheme 2
Table 1
Compound 1a-d reacted with anthranilonitrile 9a and
methylanthranilate 9b to yield the cis enaminones 11a-f.
The 1H NMR showed the presence of a mixture of the cis
Relative concentration of cis and trans form of enaminones 11, 12 as
1
indicated from H NMR
1
Compounds
Cis form
Trans form
form 11 and trans form 11'. H NMR indicated the pre-
dominance of the cis form (cf. Table 1 for relative concen-
tration of cis and trans forms in the mixture as indicated
from H NMR). Predominance of cis form is a result of
hydrogen bonding. Although the trans form can also be
stabilized through hydrogen bonding with ester group, it
seems that this effect does not give as much stability to the
trans form.
11b
11e
11f
12a
12c
12e
7
4
4.2
6.5
6
1
1
1
1
1
1
1
4
Similarly, trans 14b was formed from the reaction of 1b
with morpholine.
Similar to established behavior of enaminones toward
aromatic diazonium salts [8,9] 1b couples with benzene
diazonium chloride to yield the arylhydrazone 15 as major
Similarly, the reaction of 1a-c with 2-aminocyclohexene
thiophene-3-nitrile 10a and the reaction of 1b,e with ethyl
2-aminocyclohexene thiophene-3-carboxylate 10b afforded
the corresponding enaminones 12a-e (c f. Scheme 3).
Scheme 3
Scheme 4
11
X
R
12
X
R
a
b
c
d
e
f
CN
CN
CN
Ph
4-ClC H
thienyl
a
b
c
d
e
CN
CN
CN
Ph
4-ClC H
2-NO C H
2 6 4
4-ClC H
6
4
6
4
CO Me Ph
CO Me 4-ClC H
CO Me 2-NO C H
2 6 4
CO Et
2
2
6
4
CO Et
furyl
2
6
4
2
2
Attempted cyclization of 11a-c into quinoline failed.
Successful cyclisation of 11d into the quinolinone 13
could be affected, on heating for five minutes in domestic

Mar-Apr 2004
Studies with Enaminones: The reaction of enaminones with Aminoheterocycles
269
7.89 (m, 9H, H-Ar), 7.62 (d, J = 9Hz, olefinic H), 8.25 (s, 1H,
NH), 12.42 (d, 1H, NH).
reaction product [10,11]. However GCMS indicated
always the presence of the formazane 16. Pure 16 could be
prepared on coupling 1ab with excess benzene diazonium
chloride in DMF solution at 0 °C. The reaction of 2 with
aminoazoles afforded the azolylpyridones 17 and 18
(Scheme 4).
Anal. Calcd. for C
H N O: C, 75.69; H, 6.03; N, 13.24 %.
20 19 3
Found: C, 75.60; H, 6.00; N, 13.20.
1-(4-Chlorophenyl)-3-(2H-[1,2,4]triazol-3-ylamino)-propenone
(4d).
This compound was obtained in 66 % yield, mp 136-38 °C; IR
(KBr): ν 3355-3230 (NH), 3022 (CH, olefinic), 2912 (CH,
EXPERIMENTAL
-1
aliphatic), 1652 cm (CO); H NMR (d -DMSO): δ = 6.54 (d, J =
1
6
9Hz, olefinic H), 6.95-7.85 (m, 4H, H-Ar), 7.45 (d, J = 9Hz, olefinic
All melting points were measured on Gallenkamp electrother-
mal melting point apparatus and are uncorrected. IR spectra were
recorded as KBr pellets on a Pye Unicam SP 3-300
Spectrophotometer. H NMR spectra were recorded in deuterated
dimethylsulfoxide (d -DMSO): or deutrated chloroform (CDCl )
H), 8.25 (s, 1H triazoleH-5), 8.65 (s, 1H, NH), 12.42 (d, 1H, NH).
Anal. Calcd. for C H N OCl. C, 53.13; H, 3.65; N, 22.53; Cl,
11 9 4
14.26 %. Found: C, 53.20; H, 3.70; N, 22.50; Cl, 14.30.
1
6
3
1-Thiophen-2-yl-3-(2H-[1,2,4]triazol-3-ylamino)-propenone (4e).
at 200 MHz on a Varian Gemini NMR spectrometer using tetram-
ethylsilane (TMS) as an internal reference and results are
expressed as δ values. Mass spectra were performed on a
Shimadzu GCMS-QP 1000 Ex mass spectrometer at 70 eV.
Microwave experiments were conducted in a microwave oven
DAEWOO, edition II (KOR-8667). Elemental analyses were car-
ried out at the Microanalytical center of Cairo University.
This compound was obtained in 61% yield, mp 96-98 °C; IR
(KBr): ν 3345-3240 (NH), 3030 (CH, olefinic), 2922 (CH,
aliphatic), 1646 cm-1 (CO); 1H NMR (d6-DMSO): δ = 6.35 (d,
J = 9Hz, olefinic H), 7.05-7.70 (m, 3H, thiophene H), 7.35 (d, J =
9Hz, olefinic H), 8.14 (s, 1H triazoleH-5), 8.45 (s, 1H, NH),
12.52 (d, 1H, NH).
Anal. Calcd. for C H N OS: C, 49.08; H, 3.66; N, 25.44; S,
9 8 4
14.56 %. Found: C, 49.0; H, 3.70; N, 25.50; S, 14.60.
Preparation of Pyrazole Derivatives 4 a - c and Tr i a z o l e
Derivatives 4d-f.
1-p-Tolyl-3-(2H-[1,2,4]triazol-3-ylamino)-propenone (4f).
General Procedure.
This compound was obtained in 65 % yield, mp 103-105 °C;
IR (KBr): ν 3365-3250 (NH), 3020 (CH, olefinic), 2918 (CH,
To a solution of each of enaminone 1b,d,f (10 mmole) in
ethanol (20 ml), 4-phenyl-3-methyl-5-pyrazoleamine 3a or 3(5)-
amino1H-triazole 3b (10 mmole) was added. The reaction mix-
ture was refluxed for 6 h. The solid product formed on evapora-
tion the excess solvent was collected by filtration and crystallized
from ethanol to give 4a-f respectively.
-1
1
aliphatic), 1655 cm (CO); H NMR (d -DMSO): δ = 2.38 (s,
6
3H, CH ), 6.70(d, J = 9 Hz, olefinic H), 7.25-7.85 (m, 4H, H-Ar),
3
7.65 (d, J = 9 Hz, olefinic H), 8.28 (s, 1H triazole H-5), 8.55 (s,
1H, NH), 12.62 (d, 1H, NH).
Anal. Calcd. for C
H N O: C, 63.15; H, 5.30; N, 24.55 %.
12 12 4
Found: C, 63.20; H, 5.20; N, 24.50.
1-(4-Chloro phenyl)-3-(5-methyl-4-phenyl-2H- p y r a z o - 3 -
ylamino)-propenone (4a).
Cyclization of 4a-c into Pyrazolo[1,5-a]pyrimidine Derivatives
5a-c and 4d-f into Triazolo[1,5-a]pyrimidine Derivatives 5d-f.
This compound was obtained in 76 % yield, mp 91-92 °C; IR
(KBr): ν 3350-3240 (NH), 3024 (CH, olefinic), 2916 (CH,
General Procedure.
-1
aliphatic), 1650 cm (CO); H NMR (d -DMSO): δ = 2.85 (s,
1
6
3H, CH ), 5.95 (d, J = 9Hz, olefinic H), 7.14-8.18 (m, 9H, H-Ar),
A solution of each of 4a-f (10 mmole) was refluxed in pyridine
(20 ml) for 2h, then 1ml of concentrated hydrochloric acid was
added and the reflux continued for further one hour. After cool-
ing, the reaction mixture was poured into ice-cold water, the solid
precipitate so formed was filtered off and recrystalized from
ethanol to afford 5a-f respectively.
3
7.50 (d, J = 9Hz, olefinic H), 8.10 (s, 1H, NH), 12.02 (d, 1H,
+
NH); MS (EI, 70 eV): m/z (%)= 337 [M , (37)].
Anal. Calcd. for C
H N Ocl: C, 67.56; H, 4.77; N, 12.44;
19 16 3
Cl, 10.49 %. Found: C, 67.70; H, 4.60; N, 12.50; Cl, 10.60.
3-(5-Methyl-4-phenyl-2 H-pyrazo-3-ylamino)-1-thiophen-2-yl-
propenone (4b).
7-(4-Chlorophenyl)-2-methyl-3-phenylpyrazolo[1,5- a]pyrimi-
dine (5a).
This compound was obtained in 71% yield, mp 96-97 °C; IR
(KBr): ν 3350-3244 (NH), 3020 (CH, olefinic), 2918 (CH,
1
This compound was obtained in 77% yield mp 196-198 °C; H
-1
aliphatic), 1660 cm (CO); H NMR (d -DMSO): δ = 2.80 (s, 3H,
1
NMR (d -DMSO): δ = 2.84 (s, 3H, CH ), 7.14-8.28 (m, 11H, H-
13
6
Ar), C NMR (d -DMSO): δ = 18.65, 122.20, 124.90, 127.40,
3
6
CH ), 5.90 (d, J = 9Hz, olefinic H), 7.10-7.85 (m, 8H, H-Ar), 7.42
6
128.10, 128.62, 129.05, 129.87, 132.60, 133.90, 135.10, 136.70,
3
(d, J = 9Hz, olefinic H), 8.35 (s, 1H, NH), 12.22 (d, 1H, NH).
142.20, 158.20, 165.10.Anal. Calcd. for C
H, 4.41; N, 13.14, Cl, 11.09 %. Found: C, 71.30; H, 4.40; N,
13.20, Cl, 11.10.
H N Cl. C, 71.36;
19 14 3
Anal. Calcd. for C
H N OS: C, 66.00; H, 4.89; N, 13.58; S,
17 15 3
10.36 %. Found: C, 65.90; H, 4.90; N, 13.50; S, 10.30.
3 - ( 5 - M e t h y l - 4 - p h e n y l - 2 H- p y r a z o - 3 - y l a m i n o ) - 1 - p - t o l y l -
propenone (4c).
2-Methyl-3-phenyl-7-thiophen-2-yl-pyrazolo[1,5- a]pyrimidine
(5b).
This compound was obtained in 65 % yield mp 110-111 °C; IR
(KBr): ν 3360-3254 (NH), 3015 (CH, olefinic), 2921 (CH,
This compound was obtained in 73% yield mp 158-160 °C; IR
-1
(KBr): ν 2925 (CH, aliphatic), cm ; H NMR (d -DMSO): δ =
1
-1
aliphatic), 1645 cm (CO); H NMR (d -DMSO): δ = 2.39 (s,
1
6
6
3H, CH ), 2.75 (s, 3H, CH ), 5.98 (d, J = 9Hz, olefinic H), 7.05-
2.82 (s, 3H, CH ), 7.10-7.65 (m, 10H, H-Ar).
3
3
3

270
S. Almazroa, M. H. Elnagdi and A. M. Salah El-Din
Vol. 41
Anal. Calcd. for C
H
N S: C, 70.08; H, 4.50; N, 14.42; S,
3
General procedure.
17 13
11.00 %. Found: C, 70.10; H, 4.60; N, 14.50, S, 10.90.
2-Methyl-3-phenyl-7-p-tolyl-pyrazolo[1,5-a]pyrimidine (5c).
This compound was obtained in 65% yield mp 178-180 °C; IR
To a solution of each of compounds 1a-d (10 mmole) in diox-
ane (20 ml), was added (10 mmole) of each of anthranilonitrile
9 a, methylanthranilate 9 b, 2-amino-cyclohexene thiophene-3-
nitrile 1 0 a, ethyl 2-aminocyclohexene thiophene-3-carboxylate
10b. The reaction mixture was refluxed for 8 h in each case and
left to cool over night. The precipitated solid in each case was
separated by filtration and recystallized from the proper solvent.
-1
1
(KBr): ν 2918 (CH, aliphatic), cm ; H NMR (d -DMSO): δ =
6
2.35 (s, 3H, CH ), 2.85 (s, 3H, CH ), 7.05-7.78 (m, 11H, H-Ar).
3
Anal. Calcd. for C
Found: C, 80.30; H, 5.70; N, 14.0.
3
H N : C, 80.24; H, 5.72; N, 14.04 %.
20 17 3
2-(3-Oxo-3-phenylpropenylamino)benzonitrile (11a).
7-(4-Chlorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine (5d).
This compound was obtained in 75% yield mp 123-125 °C
(EtOH); IR (KBr): ν 3350-3244 (NH), 3018 (CH, olefinic), 2925
1
This compound was obtained in 72% yield mp 226-228 °C; H
NMR (d -DMSO): δ = 7.14-8.25 (m, 6H, H-Ar), 8.50 (s, 1H, tri-
6
azole H-5).
-1
1
(CH, aliphatic), 2218 (CN), 1635 cm (CO); H NMR (d -
6
DMSO): δ = 6.45 (d, J = 9Hz, olefinic H), 7.05-7.90 (m, 9H, H-
Ar), 7.78 (d, J = 9Hz, olefinic H), 12.20 (d, 1H, NH), -MS (EI, 70
+
EV): m/z (%) = 248(36) [M ].
Anal. Calcd. for C H N O: C, 77.40; H, 4.87; N, 11.28 %.
16 12 2
Found: C, 77.30; H, 4.90; N, 11.30.
Anal. Calcd. for C H N Cl: C, 57.28; H, 3.06; N, 24.29; Cl,
11
7 4
15.37 %. Found: C, 57.30; H, 3.10; N, 24.20; Cl, 15.40.
7-(Thiophen-2-yl-[1,2,4]triazolo[1,5-a]pyrimidine (5e).
This compound was obtained in 72% yield mp 180-182 °C;
1
H NMR (d -DMSO): δ = 7.0-7.30 (m, 3H, H, thiphene), 7.55 (d,
6
2-[3-(4-Chlorophenyl)-3-oxo-propenylamino)benzonitrile (11b).
1H, pyrimidine H), 8.40 (s, 1H, triazole H-5) 8.88 (d, 1H, pyrim-
idine H).
Anal. Calcd. for C H N S: C, 53.45; H, 2.99; N, 27.70; S,
This compound was obtained in 71% yield mp 133-135 °C
(EtOH); IR (KBr): ν 3341-3238 (NH), 3019 (CH, olefinic), 2920
9
6 4
-1
(CH, aliphatic), 2221 (CN), 1639 cm (CO); H NMR (d -
1
6
15.85 %. Found: C, 53.50; H, 3.10; N, 27.60; S, 15.90.
DMSO): δ = 6.55 (d, J = 9Hz, olefinic H), 7.0-7.95 (m, 8H, H-
Ar), 7.71 (d, J = 9Hz, olefinic H), 12.40 (d, 1H, NH), -MS (EI, 70
7-p-Tolyl-[1,2,4]triazolo[1,5-a]pyrimidine (5f).
+
EV): m/z (%) = 282 (40) [M ].
Anal. Calcd. for C H N OCl: C, 67.97; H, 3.92; N, 9.91; Cl,
This compound was obtained in 75% yield mp 188-190 °C; IR
-1
(KBr): ν 2914 (CH, aliphatic), cm ; H NMR (d -DMSO): δ =
1
16 11 2
12.54 %. Found: C, 68.00; H, 4.00; N, 9.90; Cl, 12.50.
6
2.37 (s, 3H, CH ), 7.15-7.78 (m, 5H, H-Ar), 8.30 (s, 1H, triazole
3
H-5), 8.55 (sd, 1H, pyrimidine H).
2-(3-Oxo-3-thiophen-2-yl-propenylamino)benzonitrile (11c).
Anal. Calcd. for C
Found: C, 68.60; H, 4.70; N, 26.70.
H N : C, 68.56; H, 4.79; N, 26.65 %.
12 10 4
This compound was obtained in 75% yield mp 114-116 °C
(EtOH); IR (KBr): ν 3350-3304 (NH), 3025 (CH, olefinic), 2920
-1
(CH, aliphatic), 2214 (CN), 1630 cm (CO); H NMR (d -
1
General Procedure for the Preparation of 8a,d,e.
6
DMSO): δ = 6.61 (d, J = 9Hz, olefinic H), 7.15-7.99 (m, 7H, H-
Ar), 7.66 (d, J = 9Hz, olefinic H), 12.30 (d, 1H, NH), -MS (EI, 70
Each of compound 1a,d,e (10 mmol) was refluxed in acetic
acid (20 ml) for 4 h after which it was cooled to room tempera-
ture. The precipitate, which formed, was collected by filtertration
and successively crystallized from ethanol/dioxane (3:1 v/v).
+
EV): m/z (%) = 254 (46) [M ].
Anal. Calcd. for C
12.61 %. Found: C, 66.10; H, 4.00; N, 11.10; S, 12.70.
H N OS: C, 66.12; H, 3.96; N, 11.02; S,
14 10 2
1,3,5-Tri-benzoylbenzene (8a).
Methyl 2-(3-oxo-3-phenylpropenylamino)benzoate (11d).
Yield (71%) mp 242-244 °C; -IR (KBr) ν
-1
= 1666 (CO),
13
max
cm - H NMR (d -DMSO): δ = 6.95-7.75 (m, 18H, Ar-H)
This compound was obtained in 65% yield mp 108-110 °C
(EtOH); IR (KBr): ν 3310-3250 (NH), 3025 (CH, olefinic), 2920
1
C
NMR (d -DMSO): δ = 127.90, 129.85, 131.96, 135.20, 136.80,
6
H
6
C
137.86, 188.50 (CO). -MS (EI, 70 EV): m/z (%) = 390(100)
-1
(CH, aliphatic), 1710, 1640 cm (CO); H NMR (d -DMSO): δ
1
6
= 3.85 (s, 3H, CH ), 6.41 (d, J = 9Hz, olefinic H), 7.05-7.90 (m,
3
9H, H-Ar), 7.70 (d, J = 9Hz, olefinic H), 12.29 (d, 1H, NH).
+
[M ].
Anal. Calcd. for C
83.10; H, 4.70.
H O : C, 83.06; H, 4.65 %. Found: C,
27 18 3
Anal. Calcd. for C
Found: C, 72.60; H, 5.40; N, 4.90.
H NO : C, 72.58; H, 5.37; N, 4.98 %.
17 15 3
1,3,5-Tri-thiopheno–2-ylbenzene (8d).
Methyl 2-[3-(4-chlorophenyl)-3-oxo-propenylamino)benzoate
(11e).
Yield (78%) mp 262-264 °C; -IR (KBr) ν
-1
= 1660 (CO),
cm - H NMR (d -DMSO): δ = 7.3-8.35 (m, 12H, Ar-H). -MS
max
1
6
H
This compound was obtained in 68% yield mp 114-115 °C
(EtOH); IR (KBr): ν 3315-3250 (NH), 3023 (CH, olefinic), 2924
+
(EI, 70 EV): m/z (%) = 408(8.0) [M ].
Anal. Calcd. for C O S : C, 61.74; H, 2.96; S, 23.55 %.
H
21 12
3 3
-1
(CH, aliphatic), 1708, 1642 cm (CO); H NMR (d -DMSO): δ
1
6
= 3.89 (s, 3H, CH ), 6.42 (d, J = 9Hz, olefinic H), 7.05-8.10 (m,
Found: C, 61.70; H, 3.00; S, 23.50.
1,3,5-Tri-furano-2-ylbenzene (8e).
yield (70%) mp 238-240 °C; -IR (KBr) ν
3
8H, H-Ar), 7.60 (d, J = 9Hz, olefinic H), 13.10 (d, 1H, NH).
Anal. Calcd. for C H NO Cl: C, 64.67; H, 4.47; N, 4.44; Cl,
17 14 3
11.23 %. Found: C, 64.70; H, 4.40; N, 4.50; Cl, 11.30.
= 1654 (CO),
max
-1
1
cm - H NMR (d -DMSO): δ = 6.85-8.10 (m, 12H, Ar-H).
6
Anal. Calcd. for C
70.10; H, 3.40.
H
O : C, 70.00; H, 3.36 %. Found: C,
H
21 12
Methyl 2-[(3-(2-nitrophenyl)-3-oxo-propenylamino)benzoate (11f).
6
This compound was obtained in 69% yield mp 120-122 °C
(EtOH); IR (KBr): ν 3320-3240 (NH), 3021 (CH, olefinic), 2922
Preparation of enaminones 11a-f and 12a-e.

Mar-Apr 2004
Studies with Enaminones: The reaction of enaminones with Aminoheterocycles
271
-1
(CH, aliphatic), 1715, 1640 cm (CO); H NMR (d -DMSO): δ
1
3-Benzoyl-1H-quinolin-4-one (13).
6
= 3.85 (s, 3H, CH ), 6.25 (d, J = 9Hz, olefinic H), 7.14-7.98 (m,
3
8H, H-Ar), 7.72 (d, J = 9Hz, olefinic H), 12.82 (d, 1H, NH).
Anal. Calcd. for C H N O : C, 62.58; H, 4.32; N, 8.58 %.
17 14 2 5
Found: C, 62.60; H, 4.40; N, 8.60.
Compound 11a (10 mmol) was heated for 3 minutes in domestic
microwave oven at full power. The residue cooled to deposit a solid,
which was crystallized from DMF/EtOH (1:2) to afford 13; yield
(70%) mp 230-232 °C; IR (KBr): ν 3340-3280 (NH), 1670, 1650
-1
1
cm (CO); H NMR (d -DMSO): δ = 685-7.95 (m, 9H, H-Ar) 8.31
13
2-(3-Oxo-3-phenylpropenylamino)-4, 5, 6, 7-tetrahydrobenzo -
[b]thiophene-3-carbo-nitrile (12a).
6
(s, 1H), 8.95 (s, 1H, NH), 12.12 (d, 1H, NH) C NMR (d -DMSO):
6
δ = 115.90, 116.30, 118.20, 122.80, 128.60, 129.20, 131.10, 133.95,
This compound was obtained in 79% yield mp 168-170 °C
(AcOH); IR (KBr): ν 3350-3154 (NH), 3018 (CH, olefinic), 2925
135.10, 137.25, 148.15, 155.30, 184.40 (CO), 188.20 (CO).
Anal. Calcd. for C H NO : C, 77.10; H, 4.45; N, 5.62 %.
16 11
Found: C, 76.90; H, 4.60; N, 5.70.
2
-1
(CH, aliphatic), 2210 (CN), 1640 cm (CO); H NMR (d -
1
6
DMSO): δ = 1.82 (m, 4H), 2.75 (m, 4H), 6.65 (d, J = 9Hz,
olefinic H), 7.10-7.89 (m, 5H, H-Ar), 7.62 (d, J = 9Hz, olefinic
H), 10.99 (d, 1H, NH).
Preparation of piperidine-1-yl propenone 14a-d and 3-mor-
pholin-4-yl-1-(4-chloro-phenyl)propenone 14e.
Anal. Calcd. for C
10.40 %. Found: C, 70.10; H, 5.30; N, 9.10; S, 10.50.
H N OS: C, 70.10; H, 5.23; N, 9.08; S,
18 16 2
General procedure.
Each of compounds 1a-c,f (10 mmol) was boiled in excess of
piperidine, 1b was boiled with morpholine, for 3 minutes then
left to cool to room temperature. The solid so formed in each case
was collected by filtertration and recystallized from ethanol to
afford 14a-e respectively.
2-[3-(4-Chlorophenyl)-3-oxo-propenylamino]-4,5,6,7-tetrahy -
drobenzo[b]thiophene-3-carbonitrile (12b).
This compound was obtained in 79% yield mp 178-180 °C; IR
(KBr): ν 3355-3159 (NH), 3018 (CH, olefinic), 2922 (CH,
-1
1
aliphatic), 2222 (CN), 1645 cm (CO); H NMR (d -DMSO): δ
6
1-Phenyl-3-piperidin-1-yl-propenone (14a).
= 1.80 (m, 4H), 2.79 (m, 4H), 6.60 (d, J = 9Hz, olefinic H), 7.15-
7.95 (m, 4H, H-Ar), 7.69 (d, J = 9Hz, olefinic H), 11.90 (d, 1H,
This compound was obtained in 79% yield mp 96-98 °C; IR
-1
(KBr): ν 3012 (CH, olefinic), 2939 (CH, aliphatic), 1635 cm
1
(CO); H NMR (d -DMSO): δ = 1.50 (m, 6H, 3CH ), 3.40 (m,
+
NH); MS (EI, 70 EV): m/z (%) = 342 (43) [M ].
6
4H, [CH ] N), 5.96 (d, 1H, J = 13Hz, olefinic H), 7.30 (d, 1H, J
2
Anal. Calcd. for C
H N OSCl: C, 63.06; H, 4.41; N, 8.17; S,
18 15 2
9.35 %. Found: C, 63.10; H, 4.30; N, 8.10; S, 9.50.
2 2
= 13Hz, olefinic H), 7.40-7.85 (m, 5H, Ar-H); -MS (EI, 70 EV):
+
m/z (%) = 215 (87) [M ].
2-[3-(2-Nitrophenyl)-3-oxo-propenylamino]-4,5,6,7-tetrahydro-
benzo[b]thiophene-3-carbonitrile (12c).
A n a l. Calcd. for C
Found: C, 78.20; H, 8.00; N, 6.50.
H NO: C, 78.10; H, 7.96; N, 6.51 %.
14 17
This compound was obtained in 74% yield mp 138-140 °C
(EtOH); IR (KBr): ν 3335-3169 (NH), 3012 (CH, olefinic), 2920
1-(4-Chlorophenyl)-3-piperidin-1-yl-propenone (14b).
This compound was obtained in 72% yield mp 132-134 °C; IR
-1
1
(CH, aliphatic), 2220 (CN), 1640 cm (CO); H NMR (d -
6
DMSO): δ = 1.82 (m, 4H), 2.76 (m, 4H), 6.61 (d, J = 9Hz,
olefinic H), 7.65-8.10 (m, 4H, H-Ar), 7.68 (d, J = 9Hz, olefinic
H), 11.90 (d, 1H, NH).
Anal. Calcd. for C H N O S: C, 61.18; H, 4.28; N, 11.89; S,
18 15 3 3
9.07 %. Found: C, 61.20; H, 4.30; N, 11.90; S, 9.10.
-1
(KBr): ν 3019 (CH, olefinic), 2935 (CH, aliphatic), 1631 cm
1
(CO); H NMR (d -DMSO): δ = 1.56 (m, 6H, 3CH ), 3.44 (m,
6
2
4H, [CH ] N), 5.95 (d, 1H, J = 14Hz, olefinic H), 7.44 (d, 2H Ar-
2 2
H), 7.65 (d, 1H, J = 14Hz, olefinic H), 7.88 (d, 2H Ar-H).
Anal. Calcd. for C
H NOCl: C, 67.33; H, 6.46; N, 5.61; Cl,
14 16
14.20 %. Found: C, 67.30; H, 6.50; N, 5.60; Cl, 14.10.
1-(2-Nitrophenyl)-3-piperidin-1-yl-propenone (14c).
This compound was obtained in 75% yield mp 136-137 °C; IR
Ethyl 2-[3-(4-Chlorophenyl)-3-oxo-propenylamino]-4,5,6,7-
tetrahydrobenzo[b]thiophene-3-carboxylate (12d).
This compound was obtained in 74% yield mp 128-130 °C
(EtOH); IR (KBr): ν 3350-3175 (NH), 3018 (CH, olefinic), 2922
-1
(KBr): ν 3010 (CH, olefinic), 2936 (CH, aliphatic), 1645 cm
1
(CO); H NMR (d -DMSO): δ = 1.54 (m, 6H, 3CH ), 3.36 (m,
-1
(CH, aliphatic), 1695, 1645 cm (CO); H NMR (d -DMSO): δ
1
6
= 1.23 (t, 3H, CH ), 1.60 (m, 4H), 2.70 (m, 4H), 4.15 (q, 2H,
6
4H, [CH ] N), 5.96 (d, 1H, J = 13Hz, olefinic H), 7.60 (d, 1H, J
2
3
CH ), 5.92 (d, 1H, J = 9Hz, olefinic H), 7.15-7.98 (m, 4H, H-Ar),
2 2
= 13Hz, olefinic H), 7.68-8.14 (m, 4H, Ar-H).
2
7.50 (d, 1H, J = 9Hz, olefinic H), 11.99 (d, 1H, NH).
Anal. Calcd. for C
Found: C, 64.50; H, 6.30; N, 10.70.
H N O : C, 64.60; H, 6.20; N, 10.76 %.
14 16 2 3
Anal. Calcd. for C
H NO SCl: C, 61.61; H, 5.17; N, 3.59; S,
20 20 3
8.22 %. Found: C, 61.60; H, 5.20; N, 3.60; S, 8.20.
3-Piperidin-1-yl-1-p-tolyl-propenone (14d).
This compound was obtained in 75% yield mp 125-127 °C; IR
Ethyl 2-(3-furan-2-yl-3-oxo-propenylamino)-4,5,6,7-tetrahydro-
benzo[b]thiophene-3-carboxylate (12e).
-1
(KBr): ν 3018 (CH, olefinic), 2930 (CH, aliphatic), 1640 cm
1
(CO); H NMR (d -DMSO): δ = 1.52 (m, 6H, 3CH ), 2.35 (s,
This compound was obtained in 71% yield mp 148-150 °C
(EtOH); IR (KBr): ν 3355-3165 (NH), 3018 (CH, olefinic), 2922
6
3H, CH ), 3.39 (m, 4H, [CH ] N), 5.99 (d, 1H, J = 14Hz, olefinic
2
3
2 2
-1
(CH, aliphatic), 1700, 1645 cm (CO); H NMR (d -DMSO): δ
1
6
= 1.12 (t, 3H, CH ), 1.60 (m, 4H), 2.65 (m, 4H), 4.11 (q, 2H,
H), 7.40 (d, 1H, J = 14Hz, olefinic H), 7.10-7.85 (m, 4H, Ar-H).
A n a l. Calcd. for C NO: C, 78.56; H, 8.35; N, 6.11 %.
Found: C, 78.50; H, 8.30; N, 6.10.
3
CH ), 5.96 (d, 1H, J = 9Hz, olefinic H), 6.6 (m, 1H, furan H-4),
H
15 19
2
7.23 (d, 1H, furan H-3), 7.30 (d, 1H, J = 9Hz, olefinic H), 7.91 (d,
1H, furan H-5), 11.84 (d, 1H, NH).
1-(4-Chlorophenyl)-3-morpholin-4-yl-propenone (14e).
This compound was obtained in 74% yield mp 114-116 °C; IR
Anal. Calcd. for C H NO S: C, 62.59; H, 5.54; N, 4.05; S,
18 19 4
9.28 %. Found: C, 62.50; H, 5.60; N, 4.00; S, 9.30.
-1
(KBr): ν 3025 (CH, olefinic), 2955 (CH, aliphatic), 1635 cm

272
S. Almazroa, M. H. Elnagdi and A. M. Salah El-Din
Vol. 41
1
(CO); H NMR (d -DMSO): δ = 3.45 (m, 4H, 2CH ), 3.64 (m,
was collected by filtration and crystallized from ethanol to give
17 and 18 respectively.
6
4H, [CH ] N), 6.02 (d, 1H, J = 14Hz, olefinic H), 7.40 (d, 2H Ar-
2
2 2
H), 7.60 (d, 1H, J = 14Hz, olefinic H), 7.90 (d, 2H Ar-H).
1-(5-Methyl isoxazol-3-yl)-3,5-diphenyl-1H-pyridin-4-one (17).
Anal. Calcd. for C
14.08 %. Found: C, 62.10; H, 5.60; N, 5.60; Cl, 14.10.
H NO Cl: C, 62.03; H, 5.61; N, 5.56; Cl,
13 14 2
This compound was obtained in 66% yield mp 182-184 °C; IR
-1
(KBr): ν 1655 cm (CO); H NMR (d -DMSO): δ = 2.35 (s, 3H,
1
6
CH ), 7.14-7.85 (m, 12H, H-Ar), 8.1 (s, 1H, isoxazol H-4),
3-(4-Chlorophenyl)-3-oxo-2-(phenylhydrazono)-proionaldehyde
(15).
13
C
NMR (d -DMSO): δ = 17.35 (CH ), 102.50, 122.70, 125.90,
3
6
3
127.70, 128.90, 135.10, 138.20, 148.70, 159.90, 185.70 (CO).
Anal. Calcd. for C N O : C, 76.81; H, 4.91; N, 8.53 %.
Found: C, 76.90; H, 4.80; N, 8.50.
A cold solution of benzene diazonium salt (10 mmol) was pre-
pared by a solution of sodium nitrite (10 mmol in H O) to a cold
H
21 16
2 2
2
solution of the aniline with stirring. The resulting solution of the
benzene diazonium salt was added to a cold solution of 1b (10
mmol) in ethanol (50 ml) containing sodium acetate. The reaction
mixture was stirred at room temperature for 30 min. The solid
product, so formed, was washed with water and crystallized from
the ethanol; yield (74%) mp 151-153 °C; IR (KBr): ν 3350-3240
3,5-Diphenyl-1-(2H-[1,2,4]triazol-3-yl-1H-pyridin-4-one (18)
This compound was obtained in 69% yield mp 197-198 °C; IR
-1
(KBr): ν 1665 cm (CO); H NMR (d -DMSO): δ = 7.14-7.85
1
6
(m, 12H, H-Ar), 8.5 (s, 1H, triazole H-5).
-1
1
Anal. Calcd. for C
H N O: C, 72.60; H, 4.49; N, 17.82 %.
(NH), 1695 (CHO), 1650 cm (CO); H NMR (d -DMSO): δ =
6
6.85-7.75 (m, 9H, H-Ar), 9.3 (s, 1H, CHO), 11.5 (s, 1H, NH); MS
19 14 4
Found: C, 72.60; H, 4.40; N, 17.90.
+
(EI, 70 eV): m/z (%)= 286[M , (34)].
Anal. Calcd. for C H N O Cl: C, 62.84; H, 3.87; N, 9.77,
15 11
Cl, 12.37 %. Found: C, 62.80; H, 3.80; N, 9.70, Cl, 12.40.
2 2
REFERENCES AND NOTES
[1] B. Al-Saleh, M. M. Abdel-Khalik, A. Al-Enzy, and M. H.
Elnagdi, J. Chem. Res (S), 654 1999.
3-Aza-1-(4-chlorophenyl)-3-(phenylamino)-2-(phenyldiazenyl)-
prop-2-en-1-one (16).
[2] C. Reidlinger, R. Dworczak, and H. Junek, Monatschefte
fur Chemie, 129, 1207 (1998).
[3] M. Buback, J. Abeln, T. Hubsch, C. Ott, and L. F. Tietze,
Liebigs Ann., 9 (1995).
[4] S: M. Al-Mousawi, K. S: George, and M. H. Elnagdi,
Pharmazie, 8, 54 (1999).
[5] M. M. Abdel-Khalik; M. H. Elnagdi, and S: M. Agamy;
Synthesis, 1168 (2000).
[6] B. Al-Saleh, M. M. Abdel-Khalik, A. M. Eltoukhy and M.
H. Elnagdi, J. Heterocycl. Chem. 39, 1035 (2002).
[7] M. M. Abdel-Khalik and M. H. Elnagdi; S y n t h e t i c
Commun., 32, 159 (2002).
[8] F. Al-Omran, M. M. Abdel-Khalik, and M. H. Elnagdi;
Synthesis, 91 (1997).
A cold solution of benzene diazonium salt (20 mmol) was pre-
pared as described above. The resulting solution of the benzene
diazonium salt was added to a cold solution of 1b (10 mmol) in
DMF (50 ml). The reaction mixture was stirred at room tempera-
ture for 30 min. The solid product, so formed, was washed with
water and crystallized from the DMF/ethanol (1:2); yield (64%)
-1
mp 270-272 °C; IR (KBr): ν 3350-3240 (NH), 1660 cm (CO);
1
H NMR (d -DMSO): δ = 6.85-7.75 (m, 14H, H-Ar), 12.45 (s,
+
6
1H, NH); MS (EI, 70 eV): m/z (%)= 362[M , (24)].
Anal. Calcd. for C
Cl, 9.77 %. Found: C, 66.10; H, 4.20; N, 15.60, Cl, 9.80
H N OCl: C, 66.21; H, 4.17; N, 15.44,
.
20 15 4
Preparation of azolylpyridone 17 and 18.
[9] H. A. Al-Awadi; Y. A. Ibrahim and M. H. Elnagdi,
Tetrahedron, 57, 1609 (2001).
General Procedure.
To a solution of 2 (10 mmole) in ethanol (20 ml), was added
(10 mmole) of each of 3-amino-5-methyl isoxazole or 3-amino-
1,2,4-triazole. The reaction mixture was refluxed for 6 h. The
solid product, so formed, on evaporation of the excess solvent
[10] B. Al-Saleh, N. Al-Awadi; H. Al-Kandari; M. M. Abdel-
Khalik, and M. H. Elnagdi, J. Chem. Res. (S) 16 (2000).
[11] K. M. Al-Zaydi, E. A. Hafez, and M. H. Elnagdi, J. Chem.
Research (S), 154 (2000); (M) 510 (2000).