N-azolylmethyl ketones as building blocks in heterocyclic synthesis: Synthesis of new polyfunctionally substituted azolylarylazophenols, azolylpyridones and azolylthiophenes

Article abstract of DOI:10.1002/jhet.5570400125

The title compounds 1a-b and 2 reacted with 2-arylhydrazonopropanals 3a-c to yield polyfunctionally substituted azolylarylazophenols 5 and 8. The reaction of 1b and 2 with phenylisothiocyanate in the presence of α-haloketones afforded the azolylthiophenes 12a,b and 13a,b. The reaction of 20 with α-haloketone afforded 5-benzotriazol-1 -yl-6-methyl-2-(2-oxopropylsulfanyl)nicotinonitrile 21 that was utilized as building blocks for the synthesis of condensed pyridines. Compound 21 was condensed with dimethylformamide dimethylacetal to yield thieno[2,3-b]pyridin-3-yl- N,N-dimethylformamidine derivative 22. This was further cyclized with sodium hydride to 1H-thieno[2,3-b; 4,5- b]dipyridin-4-one derivative 23.

Full text of DOI:10.1002/jhet.5570400125

Jan-Feb 2003
N-Azolylmethyl Ketones as Building Blocks in Heterocyclic
Synthesis: Synthesis of New Polyfunctionally Substituted
Azolylarylazophenols, Azolylpyridones and Azolylthiophenes
171
a
b
a
Balkis Al-Saleh , Mervat Mohammed Abdelkhalik , Morsy Ahmed El-Apasery ,
c
and Mohammed Hilmy Elnagdi *
[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
Received June 10, 2002
The title compounds 1a-b and 2 reacted with 2-arylhydrazonopropanals 3a-c to yield polyfunctionally
substituted azolylarylazophenols 5 and 8. The reaction of 1b and 2 with phenylisothiocyanate in the presence
of α-haloketones afforded the azolylthiophenes 12a,b and 13a,b. The reaction of 20 with α-haloketone
afforded 5-benzotriazol-1-yl-6-methyl-2-(2-oxopropylsulfanyl)nicotinonitrile 21 that was utilized as build-
ing blocks for the synthesis of condensed pyridines. Compound 21 was condensed with dimethylformamide
dimethylacetal to yield thieno[2,3-b]pyridin-3-yl-N,N-dimethylformamidine derivative 22. This was further
cyclized with sodium hydride to 1H-thieno[2,3-b; 4,5-b`]dipyridin-4-one derivative 23.
J. Heterocyclic Chem., 40, 171 (2003).
The reactivity of N-functionally substituted alkylbenzo-
via elimination of two water molecules. These can thus be
formulated as 5 or its positional isomer 7 formed most
likely via the presumed intermediates 4 and 6 respectively
(Scheme 2). Structure 5 has been established based on the
H NMR spectra, as it revealed two aryl singlets at δ ~ 7.76
and 8.34 ppm. This excludes completely structure 7 that
triazoles toward electrophiles has been extensively utilized
in the last decade by Katritzky et al. [1,2] and Elnagdi et
al. [3-7] in the syntheses of polyfunctionally substituted
heterocycles. Recently we have shown that N-functionally
substituted pyrazolyl [8], N-1,2,4-triazolyl and N-benzimi-
dazolyl-methyl ketones [9], also furnished carbanions
under mild conditions. This enabled ready coupling with
aromatic diazonium salts and condensation with dimethyl-
formamide dimethylacetal. In conjunction with this work
we report our finding on the reactivity of azolylmethyl
ketones of types 1 and 2 (Scheme 1) toward carbon elec-
trophiles in neutral and basic conditions.
1
Thus, it has been found that 1a,b and 2 react with 2-aryl-
hydrazonopropanals 3a-c to yield products of condensation

172
B. Al-Saleh, M. M. Abdelkhalik, M. A. El-Apasery, and M. H. Elnagdi
Vol. 40
Scheme 4
could have resulted, as it should display two doublets in its
H NMR spectrum. Similarly, compound 2 reacted with 3a-
1
c to yield 8a-c. Similar to the recently reported behavior of
1a toward phenylisothiocyanate [7], compound 1b reacted
with phenylisothiocyanate and α-haloketones in dimethyl
formamide in the presence of potassium hydroxide to yield
the azolylthiophenes 11a,b (Scheme 3). These are believed
to be formed via intermediacy of 9 and 10a,b. The possible
formation of thiazoles 12a,b was readily excluded based on
1
H NMR which indicated in each case the presence of NH
signal at δ ~ 9.5 ppm. Similarly, compound 2 reacted with
phenylisothiocyanate and α-haloketones under similar
reaction conditions to yield 13a,b. It is of value to report
that in earlier work [7], thiazoles were formed from reac-
tion of 1c with the same reagents under the same reaction
conditions, demonstrating dependency of the final product
on the nature of the utilizing ketone.
1a was then investigated to access complex heterocyclic sys-
tems (Schemes 5 and 6). Accordingly, dimethylformamide
dimethylacetal condensed with 1a yielding the enaminone
18 [7]. Compound 18 reacted with cyanothioacetamide to
Scheme 3
1
yield products that were formulated as 20 rather than 19. H
NMR revealed pyridine H proton at δ = 8.01 ppm as singlet.
4
For compound 19, this proton should appear as a doublet
confirming this structural assignment. Compound 20 reacted
with chloroacetone to yield 5,6-disubstituted-2-(2-oxopropy-
lsulfanyl)-nicotinonitrile 21, this is in contrast to the reported
direct formation of 1-(3-amino-5-benzotriazol-1-yl-6-
methylthieno[2,3-b]pyridin-2-yl) derivative on reacting 20
with phenacyl bromide [11]. Compound 21 condensed with
dimethylformamide dimethylacetal affording the thieno[2,3-
b]pyridin-3-yl-N,N-dimethylformamidine derivative 22.
This was further cyclized with sodium hydride to thieno-
[2,3-b:4,5-b’]dipyridin-4-one derivative 23. It is of value to
report that H in 23 appeared at δ = 9.04 ppm as a singlet, this
9
low field shift is a result of deshielding by the anisotropic
effect of the N-lone-pair.
Scheme 5
In light of these results, another electrophile was treated
under an alkaline condition (Scheme 4). In fact, the reac-
tion of 1c with benzylidenemalononitrile in ethanolic
piperidine has afforded a product of molecular formula
C
H N O. This is assumed to be 17, formed via
24 15 5
rearrangement of the initially formed 4H-pyrane 15 into
the 1,2,3,4-tetrahydropyridine 16 that auto-oxidized under
reaction conditions into the pyridone 17. Ready oxidation
of dihydroazines into azines has been reported earlier
under mild conditions [10].
One may thus conclude that attaching a methylene
ketone to the ring nitrogen in benzotriazole, benzimida-
zole, triazole and imidazole activate the methylene
moiety toward carbon electrophiles. Thus enabling the
To increase the synthetic scope on the utility of these
types of substrates, chemical modification of the synthon

Jan-Feb 2003
N-Azolylmethyl Ketones as Building Blocks in Heterocyclic Synthesis
173
Scheme 6
This compound was obtained in 77% yield (3.01 g); mp. 217°;
-1
ir (KBr) ν
= 3432 (OH) cm ; MS (EI, 70 EV): m/z (%) = 391
max
+
1
[M ]; H nmr (deuteriochloroform): δ = 7.37 (s, 1H, H ), 7.48-
H
2
DMFDMA
7.56 (m, 7H, arom. H), 7.59-7.64 (m, 4H, arom. H), 7.67-7.69 (m,
2H, arom. H), 7.99 (s, 1H, H ), 8.19 (d, 1H, J = 8.4 Hz, benzo-
5
13
triazolyl-H), 11.55 (s, 1H, OH); C NMR (deuteriochloroform):
δ
= 156.01, 152.99, 145.16, 144.07, 143.90, 142.46, 138.44,
C
135.00, 131.76, 131.37, 130.24, 128.79, 124.20, 124.04, 123.39,
122.97, 120.51, 118.92, 115.64, 111.85.
Anal. Calcd. for C H N O (391.42): C, 73.64; H, 4.38; N,
24 17
5
17.89. Found C, 73.64; H, 4.53; N, 17.62.
2-Benzotriazol-1-yl-4-phenylazo-5-thiophen-2-yl-phenol (5b).
This compound was obtained in 92% yield (3.65 g); mp.
-1
280°; ir (KBr) ν
= 3422 (OH) cm ; MS (EI, 70 EV): m/z
max
+
1
(%) = 397 [M ]; H nmr (DMSO): δ = 7.28 (dd, 1H, J = 4 Hz,
H
thienyl H ), 7.47-7.51 (m, 1H, thienyl H ), 7.56 (d, 1H, J = 8.0
4
3
Hz, benzotriazolyl-H), 7.59-7.65 (m, 5H, Ph), 7.68 (s, 1H, H ),
2
synthesis of a variety of polyfunctionally substituted
azolyl and azinyl heteroaromatics. This is in contrast
with the reported ready elimination of the benzotriazole
moiety during reaction of alkyl benzotriazoles with
electrophilic reagents, no such elimination has been
observed in our systems.
7.86 (dd, 1H, J = 4.6 Hz, thienyl H ), 7.93 (m, 2H, benzotria-
5
zolyl-H), 7.97 (s, 1H, H ), 8.18 (d, 1H, J = 8.2 Hz, benzotria-
5
13
zolyl H), 11.68 (s, 1H, OH); C nmr (DMSO): δ = 155.68,
C
153.01, 145.91, 141.17, 138.19, 137.15, 134.37, 132.28,
132.17, 130.42, 129.22, 128.98, 128.35, 125.17, 124.43,
124.11, 120.22, 116.62, 116.32, 112.63.
Anal. Calcd. for C H N OS (397.38): C, 66.49; H, 3.80; N,
22 15
5
17.63; S, 8.05. Found C, 66.72; H, 4.08; N, 17.52; S, 7.84.
EXPERIMENTAL
2-Benzotriazol-1-yl-5-furan-2-yl-4-phenylazo-phenol (5c).
All melting points are uncorrected. IR spectra were recorded in
KBr with a Pye Unicam SP 1100 spectrophotometer. H NMR
This compound was obtained in 91% yield (3.46 g); mp.
1
-1
260°; ir (KBr) ν
(%) = 381 [M ]; H nmr (DMSO): δ = 6.76-6.78 (m, 1H,
= 3435 (OH) cm ; MS (EI, 70 EV): m/z
max
spectra were recorded on a Varian EM-390 400 MHz spectrome-
+
1
H
2
ter in deuteriochloroform or [ H ] DMSO as solvent and TMS as
6
furyl H ), 7.08 (d, 1H, J = 3.4 Hz, furyl H ), 7.47-7.51 (m, 1H,
4
3
internal standard; chemical shifts are reported in δ units (ppm).
Mass spectra were measured on MS 30 and MS 9 (AEI) instru-
ments operating at 70 eV. Microanalyses were performed on a
LECO CHNS-932. Compounds 1a,b and 2 were prepared fol-
lowing published procedure [12,13,9].
furyl H ), 7.56-7.64 (m, 5H, Ph), 7.76 (s, 1H, H ), 7.89 (m, 2H,
5
6
benzotriazolyl H), 7.93 (s, 1H, H ), 8.01-8.02 (m, 1H, benzo-
3
triazolyl-H), 8.17 (d, 1H, J = 8.1 Hz, benzotriazolyl H), 11.54
13
(s, 1H, OH); C nmr (DMSO): δ = 155.56, 153.08, 149.58,
C
145.89, 145.22, 140.97, 134.35, 132.57, 132.18, 130.49,
128.95, 125.16, 123.94, 123.71, 120.21, 116.44, 116.38,
114.02, 113.97, 112.65.
2-Benzotriazol-1-yl-1-phenylethanone (1c).
A mixture of benzotriazole (1.19 g, 10 mmol), and phenacyl
bromide (1.99 g, 10 mmol), in DMF (20 ml) and in the presence
of sodium hydroxide (0.05 g) was heated under reflux for 2 h.
The solvent was reduced under vacuum, poured into water and
neutralized with diluted hydrochloric acid solution to deposit a
Anal. Calcd. for C H N O (381.38): C, 69.28; H, 3.96; N,
22 15
5 2
18.36. Found C, 69.18; H, 4.11; N, 18.13.
4-Benzimidazol-1-yl-6-phenylazo-biphenyl-3-ol (5d).
This compound was obtained in 80% yield (3.12 g); mp. 288°;
solid, which was crystallized from ethanol. Yield: 1.70 g (72 %);
-1
ir (KBr) ν
= 3420 cm (OH); MS (EI, 70 EV): m/z (%) = 390
max
-1
mp 115°. ir (KBr) ν
= 1689 (CO) cm ; MS (EI, 70 EV): m/z
+
1
max
[M ]; H nmr (DMSO): δ = 7.27 (s, 1H, H ), 7.29-7.30 (m, 2H,
H
2
+
1
(%) = 237 [M ]; H nmr (deuteriochloroform): δ = 6.11 (s, 2H,
H
arom. H), 7.38-7.40 (m, 1H, arom. H), 7.46-7.57 (m, 8H, arom.
H), 7.64-7.66 (m, 2H, arom. H), 7.77-7.79 (m, 1H, arom. H), 7.90
CH ), 7.37-7.41 (m, 2H, arom. H), 7.47-7.57 (m, 3H, arom. H),
2
7.66-7.70 (m, 1H, arom. H), 8.06-8.11 (m, 3H, arom. H).
(s, 1H, H ), 8.47 (s, 1H, benzimidazolyl H ), 11.20 (s, 1H, OH).
5
2
Anal. Calcd. for C H N O (237.25): C, 70.87; H, 4.67; N,
14 11
3
Anal. Calcd. for C H N O (390.43): C, 76.90; H, 4.65; N,
25 18
4
17.71. Found C, 70.90; H, 4.53; N, 17.69.
14.35. Found C, 77.09; H, 4.73; N, 14.26.
General Procedure for the Preparation of Compounds 5a-f.
2- Benzimidazol-1-yl-4-phenylazo-5-thiophen-2-yl-phenol (5e).
To a stirred suspension of each of compound 3a-c (10 mmol) in
ethanol (20 ml) containing potassium hydroxide (0.56 g, 10
mmol), each of compound 1a,b (10 mmol) was added. The reac-
tion mixture was heated under reflux for 2 h. The solvent was
evaporated under reduced pressure and the remaining product was
triturated with water and neutralized with hydrochloric acid to
deposit a solid, which was crystallized from ethanol/dioxane (3:1).
This compound was obtained in 85% yield (3.36 g); mp. 276°; ir
-1
(KBr) ν
= 3439 (OH) cm ; MS (EI, 70 EV): m/z (%) = 396
max
+
1
[M ]; H nmr (DMSO): δ = 7.25-7.31 (m, 3H, arom. H), 7.37-
H
7.40 (m, 1H, thienyl H ), 7.54 (d, 1H, J = 4.8 Hz, thienyl H ), 7.62-
4
3
7.35 (m, 4H, arom. H), 7.76-7.78 (m, 1H, arom. H), 7.84 (d, 1H, J =
4.6 Hz, thienyl H ), 7.88 (s, 1H, H-3), 7.92 (d, 2H, J = 8.0 Hz, ben-
5
zimidazolyl H), 8.46 (s, 1H, benzimidazolyl H ), 11.40 (s, 1H, OH);
2
13
4-Benzotriazol-1-yl-6-phenylazobiphenyl-3-ol (5a).
C nmr (DMSO): δ = 156.46, 153.03, 145.10, 143.82, 141.11,
C

174
B. Al-Saleh, M. M. Abdelkhalik, M. A. El-Apasery, and M. H. Elnagdi
Vol. 40
138.40, 136.16, 134.91, 132.02, 130.40, 128.89, 128.28, 124.26,
124.09, 123.03, 121.96, 120.49, 118.48, 116.49, 115.76, 111.87.
1-(4-Benzimidazol-1-yl-3-methyl-5-phenylaminothiophen-2-
yl)ethanone 11a.
Anal. Calcd. for C H N OS (396.38): C, 69.69; H, 4.07; N,
14.14; S, 8.07. Found C, 69.63; H, 4.18; N, 13.95; S, 7.83.
23 16
4
This compound was obtained in 75% yield (2.60 g); mp. 240°;
-1
ir (KBr) ν
= 3086 (NH), 1614 (CO) cm ; MS (EI, 70 EV):
max
+
1
m/z (%) = 347 [M ]; H nmr (deuteriochloroform): δ = 2.10 (s,
2- Benzimidazol-1-yl-5-furan-2-yl-4-phenylazo-phenol (5f).
H
3H, CH ), 2.52 (s, 3H, COCH ), 7.10-7.14 (m, 1H, arom. H),
7.17-7.23 (m, 2H, arom. H), 7.36-7.41 (m, 3H, arom. H), 7.46-
3
3
This compound was obtained in 68% yield (2.58 g); mp. 273°;
-1
ir (KBr) ν
= 3435 (OH) cm ; MS (EI, 70 EV): m/z (%) = 380
max
7.51 (m, 3H, arom. H), 8.96 (s, 1H, benzimidazolyl-H), 9.57 (br
+
1
[M ]; H nmr (DMSO): δ = 6.75 (t, 1H, J = 3.4 Hz, furyl H ),
H
4
13
s, 1H, NH); C nmr (deutereochloroform): δ = 189.9 (CO),
C
7.03 (d, 1H, J = 3.4 Hz, furyl H ), 7.28-7.30 (m, 2H, arom. H),
3
151.8, 143.6, 143.0, 142.4, 141.3, 134.0, 130.0, 124.5, 124.1,
123.7, 120.2, 119.8, 119.2, 115.7, 110.7, 29.5, 14.5.
7.36-7.38 (m, 1H, furyl H ), 7.55-7.63 (m, 3H, arom. H), 7.71 (s,
5
1H, H-6), 7.76-7.82 (m, 1H, benzoimidazolyl H), 7.84-7.87 (m,
3H, benzoimidazolyl H), 7.98 (s, 1H, H-3), 8.46 (s, 1H, benzoim-
Anal. Calcd. for C H N OS (347.36): C, 69.15; H, 4.93; N,
20 17
3
12.10; S, 9.21. Found C, 68.95; H, 5.01; N, 12.08; S, 9.00.
idazolyl H ), 11.55 (s, 1H, OH).
2
Anal. Calcd. for C H N4O (380.39): C, 72.62; H, 4.24; N,
(4-Benzimidazol-1-yl-3-methyl-5-phenylaminothiophen-2-yl)-
23 16
2
14.73. Found C, 72.88; H, 4.25; N, 14.56.
phenylmethanone (11b).
General Procedure for the Preparation of Compounds 8a-c.
This compound was obtained in 69% yield (2.82 g); mp. 150°;
-1
ir (KBr) ν
= 3055 (NH), 1606 (CO) cm ; MS (EI, 70 EV):
max
Similar reaction conditions as for compounds 7a-f using com-
pound 2 (10 mmol) were utilized. The target product 8a-c was
crystallized from ethanol/dioxane (3:1).
+
1
m/z (%) = 409 [M ]; H nmr (DMSO): δ = 1.83 (s, 3H, CH ),
H
3
7.01-7.03 (m, 1H, arom. H), 7.26-7.32 (m, 7H, arom. H), 7.50-
7.57 (m, 3H, arom. H), 7.69-7.71 (m, 2H, arom. H), 7.76-7.78 (m,
6-Phenylazo-4-[1,2,4]-triazol-1-yl-biphenyl-3-ol (8a).
1H, arom. H), 8.38 (s, 1H, benzimidazolyl H ), 9.36 (br s, 1H,
2
13
NH); C nmr (DMSO): δ = 188.3 (CO), 153.3, 145.6, 144.6,
C
This compound was obtained in 88% yield (3.0 g); mp. 230°;
142.5, 141.8, 140.8, 134.6, 132.5, 130.31, 129.4, 128.8, 124.7,
124.3, 123.6, 120.1, 119.8, 118.4, 117.4, 111.5, 15.0.
-1
ir (KBr) ν
= 3415 (OH) cm ; MS (EI, 70 EV): m/z (%) = 341
max
+
1
[M ]; H nmr (deuteriochloroform): δ = 7.38 (s, 1H, H ), 7.46-
H
2
Anal. Calcd. for C H N OS (409.43): C, 73.33; H, 4.68; N,
25 19
3
7.51 (m, 6H, arom. H), 7.55-7.57 (m, 2H, arom. H), 7.79-7.81 (m,
2H, arom. H), 8.11 (s, 1H, H ), 8.27 (s, 1H, triazolyl H ), 8.89 (s,
10.26; S, 7.81. Found C, 73.11; H, 4.74; N, 10.39; S, 7.60.
5
4
1H, triazolyl H ), 10.61 (s, 1H, OH).
2
1-(3-Methyl-5-phenylamino-4-[1,2,4]-triazol-1-yl-thiophen-2-
yl)ethanone (13a).
Anal. Calcd. for C H N O (341.36): C, 70.37; H, 4.43; N,
20 15
5
20.52. Found C, 70.31; H, 4.58; N, 9.87.
This compound was obtained in 80% yield (2.40 g); mp. 185°;
4-Phenylazo-5-thiophen-2-yl-2-[1,2,4]-triazol-1-yl-phenol (8b).
This compound was obtained in 85% yield (3.0 g); mp. 271°;
-1
ir (KBr) ν
= 3064 (NH), 1613 (CO) cm ; MS (EI, 70 EV):
max
+
1
m/z (%) = 298 [M ]; H nmr (deuteriochloroform): δ = 2.05 (s,
H
-1
3H, CH ), 2.43 (s, 3H, COCH ), 7.04-7.07 (m, 1H, arom. H),
ir (KBr) ν
= 3435 (OH) cm ; MS (EI, 70 EV): m/z (%) = 396
3 3
max
+
1
7.27-7.36 (m, 5H, arom. H), 8.26 (s, 1H, triazolyl H ), 8.77 (s,
4
[M ]; H nmr (DMSO): δ = 7.23 (t, 1H, J = 4 Hz, thienyl H ),
H
4
1H, triazolyl H ), 9.16 (br s, 1H, NH).
7.54-7.64 (m, 5H, arom. H), 7.82 (d, 1H, J = 4.2 Hz, thienyl H ),
7.94-7.96 (m, 2H, arom. H), 8.15 (s, 1H, H ), 8.32 (s, 1H, tria-
2
5
Anal. Calcd. for C H N OS (298.29): C, 60.39; H, 4.73; N,
15 14
4
3
18.78; S, 10.73. Found C, 60.59; H, 4.79; N, 18.80; S, 10.71.
zolyl H ), 9.15 (s, 1H, triazolyl H ), 11.71 (s, 1H, OH).
4
2
Anal. Calcd. for C H N OS (347.32): C, 62.24; H, 3.78; N,
20.17; S, 9.21. Found C, 62.48; H, 3.99; N, 19.95; S, 9.11.
18 13
5
(3-Methyl-5-phenylamino-4-[1,2,4]-triazol-1-yl- -thiophen-2-
yl)phenyl-methanone (13b).
5-Furan-2-yl- 4-phenylazo-2-[1,2,4]-triazol-1-yl-phenol (8d).
This compound was obtained in 72% yield (2.60 g); mp. 190°;
-1
ir (KBr) ν
= 3069 (NH), 1617 (CO) cm ; MS (EI, 70 EV):
This compound was obtained in 87% yield (2.85 g); mp. 236°;
max
+
1
-1
m/z (%) = 360.36 [M ]; H nmr (DMSO): δ = 1.88 (s, 3H,
ir (KBr) ν
= 3435 (OH) cm ; MS (EI, 70 EV): m/z (%) = 380
H
max
+
1
CH ), 7.05-7.07 (m, 1H, arom. H), 7.26-7.35 (m, 7H, arom. H),
[M ]; H nmr (DMSO): δ = 6.79 (t, 1H, J = 3.6 Hz, furyl H ),
3
H
4
7.49-7.53 (m, 3H, arom. H), 7.57-7.59 (m, 1H, arom. H), 7.65-
7.00 (d, 1H, J = 3.6 Hz, furyl H ), 7.54-7.65 (m, 4H, arom. H),
3
7.67 (m, 2H, arom. H), 8.26 (s, 1H, triazolyl H ), 8.80 (s, 1H, tri-
7.81-7.96 (m, 3H, arom. H), 8.12 (s, 1H, H ), 8.26 (s, 1H, tria-
4
3
13
azolyl H ), 9.29 (br s, 1H, NH); C nmr (DMSO): δ = 188.47,
zolyl H-4), 9.16 (s, 1H, triazolyl H ), 11.70 (s, 1H, OH).
2
C
2
153.33, 153.28, 147.62, 144.20, 141.51, 140.71, 132.54, 130.45,
Anal. Calcd. for C H N O (331.32): C, 65.25; H, 3.96; N,
18 13
5 2
129.44, 128.75, 124.66, 120.12, 119.31, 117.99, 14.87 (CH ).
21.14. Found C, 65.09; H, 4.07; N, 21.09.
3
Anal. Calcd. for C H N OS (360.36): C, 66.66; H, 4.48; N,
20 16
4
General Procedure for the Preparation of Compounds 11a,b and
13a,b.
15.55; S, 8.88. Found C, 67.00; H, 4.48; N, 15.40; S, 9.06.
5-Benzotriazol-1-yl-2-oxo-4,6-diphenyl-1,2-dihydropyridine-3-
carbonitrile (17).
A stirred suspension of each of compound 1b and 2 (10 mmol)
and phenyl isothiocyanate (1.35 g, 10 mmol) in DMF (20 ml) in
the presence of potassium hydroxide (0.06 g); α-haloketone (10
mmol) is added to the stirred solution after 10 h and the reaction
mixture is heated under reflux for 4 h. The solvent was removed
and the residue was triturated with water and neutralized with
hydrochloric acid. The solid product was crystallized from ethanol.
Benzylidenemalononitrile (1.54 g, 10 mmol) was added to a
stirred suspension of compound 1c (2.37 g, 10 mmol) in ethanol
(20 ml) in the presence of sodium hydroxide (0.5 g). The reaction
mixture was heated under reflux for 2 h. The solvent was reduced
under vacuum; poured onto water and the residue was neutralized

Jan-Feb 2003
N-Azolylmethyl Ketones as Building Blocks in Heterocyclic Synthesis
175
with diluted hydrochloric acid solution to deposit a solid, which
3H, COCH ), 3.01 (s, 6H, NMe ), 7.53 (t, 1H, J = 8.6 Hz, benzo-
3 2
was crystallized from dioxane. Yield: 2.40 g (62 %); mp. > 300°;
triazolyl-H), 7.61-7.67 (m, 2H, benzotriazolyl-H), 7.97 (s, 1H, H ),
8.23 (d, 1H, J = 8.6 Hz, benzotriazolyl-H), 8.42 (s, 1H, amidine-H).
4
-1
ir (KBr) ν
= 3060 (NH), 2229 (CN), 1672 (CO) cm ; MS
max
+
1
(EI, 70 EV): m/z (%) = 389 [M ]; H nmr (DMSO): δ = 7.00-
Anal. Calcd. for C H N OS (378.38): C, 60.31; H, 4.80; N,
H
19 18 6
7.26 (m, 10H, arom. H), 7.33-7.40 (m, 2H, benzotriazolyl-H),
7.60 (d, 1H, J = 8.6 Hz, benzotriazolyl-H), 7.78 (d, 1H, J = 8.6
Hz, benzotriazolyl-H), 13.46 (br s, 1H, NH).
22.21; S, 8.46. Found C, 60.14; H, 4.88; N, 21.98; S, 8.21.
8-Benzotriazol-1-yl-7-methyl-1H-thieno[2,3-b; 4,5-b’]dipyridin-
4-one (23).
Anal. Calcd. for C H N O (389.40): C, 74.02; H, 3.88; N,
24 15
5
To a suspension of compound 22 (3.78 g, 10 mmol) in dioxane
(20 ml), sodium hydride (0.4 g, 60 % dispersion) was added. The
reaction mixture was heated under reflux for 6 h. The solvent was
reduced under vacuum; poured into water and the residue was
neutralized with diluted hydrochloric acid solution to deposit a
17.99. Found C, 74.27; H, 4.02; N, 18.21.
5-Benzotriazol-1-yl-6-methyl-2-thioxo-1,2-dihydropyridine-3-
carbonitrile (20).
Cyanothioacetamide (1 g, 10 mmol) was added to a stirred sus-
pension of the enaminone 18 (2.30 g, 10 mmol) in ethanol (20 ml)
in the presence of few drops of triethyl amine. The reaction mixture
was heated under reflux for 2 h. The solvent was reduced under vac-
uum; poured onto water and the residue was neutralized with
diluted hydrochloric acid solution to deposit a solid, which was
solid, which was crystallized from dioxane/ethanol (1:3). Yield:
-1
2.0 g (60 %); mp. > 300 °; ir (KBr) ν
= 33.92 (OH) cm ; MS
max
+
1
(EI, 70 EV): m/z (%) = 333 [M ]; H nmr (DMSO): δ = 2.48 (s,
H
3H, CH ), 3.84 (br s, 1H, NH), 6.62 (d, 1H, J = 8.4 Hz, H ), 7.57
3
3
(t, 1H, J = 8.6 Hz, benzotriazolyl-H), 7.68 (t, 1H, J = 8.6 Hz,
benzotriazolyl-H), 7.76 (d, 1H, J = 8.4 Hz, H ), 8.26-8.30 (m,
crystallized from ethanol. Yield: 1.70 g (64 %); mp. 290°; ir (KBr)
2
13
-1
2H, benzotriazolyl-H), 9.04 (s, 1H, H ); C nmr (DMSO): δ =
ν
= 3013 (NH), 2224 (CN) cm ; MS (EI, 70 EV): m/z (%) = 267
9
C
max
+
1
161.23 (CO), 156.97, 145.92, 142.65, 134.41, 130.62, 129.93,
129.50, 128. 45, 127.65, 126.21, 125.82, 124.79, 120.65, 111.97,
111.59, 22.23.
[M ]; H nmr (deuteriochloroform): δ = 2.38 (s, 3H, CH ), 7.36-
3
7.38 (m, 1H, benzotriazolyl-H), 7.52-7.59 (m, 1H, benzotriazolyl-
H), 7.62-7.69 (m, 1H, benzotriazolyl-H), 8.01 (s, 1H, pyridyl H ),
4
8.18-8.27 (m, 1H, benzotriazolyl-H), 13.65 (br s, 1H, NH).
Anal. Calcd. for C H N5OS (333.38): C, 61.26; H, 3.33; N,
17 11
Anal. Calcd. for C H N S (267.24): C, 58.42; H, 3.39; N,
21.01; S, 9.60. Found C, 61.14; H, 3.48; N, 20.92; S, 9.87.
19 14
2
26.21; S, 11.97. Found: C, 58.51; H, 3.54; N, 25.95; S, 11.82.
Acknowledgement.
5-Benzotriazol-1-yl-6-methyl-2-(2-oxopropylsulfanyl)nicotino-
The authors are grateful to the University of Kuwait R. A. for
financial support through project Sc 103. Analytical facilities
provided by SAF are highly appreciated.
nitrile (21).
Chloroacetone (0.92 g, 10 mmol) was added to a stirred sus-
pension of compound 20 (2.67 g, 10 mmol) in DMF (20 ml) in
the presence of potassium hydroxide (0.5 g). The reaction mix-
ture was heated under reflux for 6 h. The solvent was reduced
under vacuum; poured onto water and the residue was neutralized
with diluted hydrochloric acid solution to deposit a solid, which
REFERENCES AND NOTES
[1] A. R. Katritzky, S. A. Henderson and B. Yang, J.
Heterocyclic Chem., 35, 1123 (1998).
[2] A. R. Katritzky, X. Lan, J. Z. Yang and O. V. Densiko,
Chem. Rev., 98, 409 (1998).
[3] A. Al-Naggar, M. M. Abdel-khalik and M. H. Elnagdi, J.
Chem. Res. (S), 654, (1999).
[4] H. Behbehani, M. M. Abdel-khalik and M. H Elnagdi,
Org. Prep. Proced. Int., 31, 551, (1999).
[5] S. Al-Mousawi, M. M. Abdel-khalik, S. El-Sherbiny, E.
John and M. H. Elnagdi, J. Heterocyclic Chem., 38, 949 (2000).
[6] F. Al-Omran, N. Al-Awadi, O. Youssef and M. H. Elnagdi,
J. Heterocyclic Chem., 37, 167, (2000).
[7] B. Al-Saleh, M. M. Abdel-khalik, O. A. Salah and M. H.
Elnagdi, Heteroatom Chemistry, 13, 141, (2002).
[8] M. H. Mohamed, M. M. Abdel-Khalik and M. H. Elnagdi,
J. Heterocyclic Chem., 38, 685, (2001).
[9] M. Abdel-Megid, M. H. Elnagdi and A. M. Negm, J.
Heterocyclic Chem., 39, 105 (2002).
[10] M. H. Elnagdi and A. W. Erian, Bull. Chem. Soc. Jpn., 63,
1854, (1990).
was crystallized from ethanol/dioxane (1:2). Yield: 2.60 g (80
%); mp. 259°; ir (KBr) ν
-1
= 2228 (CN), 1676 (CO) cm ; MS
max
+
1
(EI, 70 EV): m/z (%) = 323 [M ]; H nmr (deuteriochloroform):
= 2.46 (s, 1H, CH ), 2.48 (s, 1H, COCH ), 6.79 (s, 2H, CH ),
δ
H
3
3
2
7.34 (d, 1H, J = 8.4 Hz, benzotriazolyl-H), 7.50 (t, 1H, J = 8.6
Hz, benzotriazolyl-H), 7.59 (t, 1H, J = 8.6 Hz, benzotriazolyl-H),
8.08 (s, 1H, pyridyl H ), 8.20 (d, 1H, J = 8.4 Hz, benzotriazolyl-
4
13
H); C nmr (DMSO): δ = 192.37 (CO), 160.68, 157.78,
C
148.15, 145.86, 134.42, 131.60, 129.82, 128.79, 125.73, 120.58,
111.62, 106.04, 31.57 (CH ), 29.89 (CH ), 22.11 (COCH ).
Anal. Calcd. for C H N OS (323.30): C, 59.44; H, 4.05; N,
21.66; S, 9.90. Found C, 59.64; H, 4.07; N, 21.66; S, 9.68.
2
3
3
16 13
5
N’-(2-Acetyl-5-benzotriazol-1-yl-6-methyl-thieno[2,3-b]pyridin-
3-yl)-N,N-dimethylformamidine (22).
To a suspension of compound 20 (3.23 g, 10 mmol) in xylene (20
ml), dimethylformamide dimethylacetal (1,19 g, 10 mmol) was
added. The reaction mixture was heated under reflux for 4 h. The
solvent was removed and the residue cooled to deposit a solid, which
was crystallized from dioxane/ethanol (1:1). Yield: 2.50 g (65 %);
mp. 264°; ir (KBr) ν
[11] F. Al-Omran, J. Heterocyclic Chem., 37, 1219, (2000).
[12] A. R. Katritzky and J. Wu, Synthesis, 597, (1994).
[13] A. R. Katritzky and J. V. Shcherbakov, J. Heterocyclic
Chem., 33, 2031, (1996).
-1
= 1636 (CO) cm ; MS (EI, 70 EV): m/z
max
+
1
(%) = 378 [M ]; H nmr (DMSO): δ = 2.29 (s, 3H, CH ), 2.55 (s,
H
3