Facile one-pot synthesis of 4-aryl-3-methyl-1-phenylpyrazolo[3,4-b]-[1,5] benzothiazepine derivatives via a regioselective nucleophilic addition

Article abstract of DOI:10.1080/10426500490274646

4-Arylidene-3-methyl-1-phenylpyrazole-5-one reacts with 2-aminobenzenethiol in ethanol-acetic acid solution to produce a mixture of 4-aryl-3-methyl-1-phenylpyrazolo[3,4-b][1,5]benzothiazepines, 2-arylbenzothiazoles and 3-methyl-1-phenylpyrazole-5-one.

Full text of DOI:10.1080/10426500490274646

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Phosphorus, Sulfur, and Silicon and the Related
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FACILE ONE-POT SYNTHESIS OF 4-ARYL-3-METHYL-1-
PHENYLPYRAZOLO[3,4-b]-[1,5]BENZOTHIAZEPINE
DERIVATIVES VIA A REGIOSELECTIVE NUCLEOPHILIC
ADDITION
a
a
Fawi M. Abd El Latif & Eman A. El Rady
a
South Valley University , Aswan, Egypt
Published online: 11 Aug 2010.
To cite this article: Fawi M. Abd El Latif & Eman A. El Rady (2004) FACILE ONE-POT SYNTHESIS OF 4-ARYL-3-METHYL-1-
PHENYLPYRAZOLO[3,4-b]-[1,5]BENZOTHIAZEPINE DERIVATIVES VIA A REGIOSELECTIVE NUCLEOPHILIC ADDITION, Phosphorus,
Sulfur, and Silicon and the Related Elements, 179:2, 215-219, DOI: 10.1080/10426500490274646
To link to this article: http://dx.doi.org/10.1080/10426500490274646
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Phosphorus, Sulfur, and Silicon, 179:215–219, 2004
Copyright ꢀC Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490274646
FACILE ONE-POT SYNTHESIS OF
-ARYL-3-METHYL-1-PHENYLPYRAZOLO[3,4-b]-
4
[
1,5]BENZOTHIAZEPINE DERIVATIVES VIA
A REGIOSELECTIVE NUCLEOPHILIC ADDITION
Fawi M. Abd El Latif and Eman A. El Rady
South Valley University, Aswan, Egypt
(
Received March 2, 2003; accepted July 26, 2003)
4
-Arylidene-3-methyl-1-phenylpyrazole-5-one reacts with 2-amino-
benzenethiol in ethanol-acetic acid solution to produce a mix-
ture of 4-aryl-3-methyl-1-phenylpyrazolo[3,4-b][1,5]benzothiazepines,
2
-arylbenzothiazoles and 3-methyl-1-phenylpyrazole-5-one.
Keywords: 2-Arylbenzothiazoles; pyrazolo[1,5]benzothiazepine; spec-
tral characterization
Previously we have shown that 2-aminobenzenethiol 2 and its ana-
logues are useful precursor for the synthesis of seven-membered
1−4
ring.
Most of the reactions lead to the formation of a seven-membered
ring based on condensation of 2-aminophenol derivatives followed by
5
−8
cyclization.
However, the azepine derivatives are of importance in
9
,10
medicinal chemistry because of their remarkable effect.
In this
sequence, this article describes a convenient and simple route for the
preparation of pyrazolo[3,4-b][1,5]benzothiazepine derivatives.
RESULTS AND DISCUSSION
2
-Aminobenzenethiol 2 reacts directly with arylidenes 1 in ethanol solu-
tion in the presence of a catalytic amount of acetic acid to give 4-aryl-3-
methyl-1-phenylpyrazolo[3,4-b][1,5]benzothiazepines 5 predominantly,
concomitant with a minor amount of 3-methyl-1-phenylpyrazole-5-one
1
0 and 2-arylbenzthiazoles 12 (c.f. Schemes 1 and 2). Formation of the
products seems to be formed through a nucleophilic addition of the
amine function of 2 to 1 resulting in formation of the intermediate 3,
which may present in its enol form 4, which subsequently loses water
to give the target compound 5. However, if the addition starts from
2
15

2
16
F. M. A. El Latif and E. A. El Rady
SCHEME 1
the thiol function to yield the intermediates 6 and 7, the final product
1
would be 8 which is ruled out based on spectral data. H NMR spectra
(
DMSO-d6,) of 5 showed one singlet at δ = 2.1 ppm due to the protons
13
of the methyl group. However, C NMR spectra of 5 showed absorption
at 14.20 ppm assigned for methyl carbon. The lack of absorption due to

Thiazepine Derivatives
217
SCHEME 2
the NH as the lake of any singlet signal at δ <7.0 and at <90 ppm in
1
13
their H and C NMR spectra which would appear for C-4 of structure
8
demonstrates the assumption of regioselectivity of this addition.
On the other hand, it is worthy to mention that the minor amount
of colorless crystals that formed during reflux were identified as 3-
methyl-1-phenylpyrazol-5-one 10 by both spectroscopic analysis and
comparison with an authentic sample. Meanwhile, isolation of 2-
phenylbenzothiazole 12a from the reaction mixture prompt us to sug-
gest a plausible pathway forming both 10 and 12. Formation of 2-
arylbenzthiazoles 12 seems possible to proceed from the intermediate
3
which loses pyrazolone moiety 10 via broken the bond a to yield the
intermediate cation 9. Intramolecular nucleophilic attack by lone pair
electrons of the sulfur atom on the electrophilic carbon leads to the
dihydro intermediate 11 which is readily oxidized under an aerobic
conditions to give 12 (c.f. Scheme 2).
EXPERIMENTAL
All melting points were measured on a Gallen-Kamp melting point
apparatus and are uncorrected. IR spectra were recorded (potassium

2
18
F. M. A. El Latif and E. A. El Rady
bromide, ν = cm− ) were run on a Shimadzu 408 and a Pye Unicam
Spectrophotometer. The 1H, C NMR spectra (DMSO-d6, CDCl3,
δ = ppm) were recorded on a Bruker WM 300 MHz Spectrometer and
TMS was used as internal standard. Mass spectra were recorded on a
mass spectrometer MS 9 (AET) EI Mode at 70 ev. All the Microanalysis
were carried out at Microanalytical Center, Cairo University, Egypt.
1
13
Preparation of 4-Aryl-3-methyl-1-phenylpyrazolo[3,4-b]-
[
1,5]benzothiazepine Derivatives 5
General Procedure
To ethanol solution (20 ml) of 1a (1.04 g, 4 mmol) an equimoluar
amount of 2 (0.52 g, 4 mmol) was added. The mixture was boiled un-
der reflux in presence of 0.1 ml of acetic acid for 3 h. The pyrazolone
1
0 that crystallized after cooling at room temperature was filtered and
washed with ethanol. The residue was concentrated in vacuum where-
upon 2-phenylbenzothiazole 12a was isolated after addition of 5 ml of
methanol, filtered, and washed with cold methanol. The remainder so-
lution was diluted with a mixture of 3 ml of water acidified by 0.1 ml of
concentrated hydrochloric acid. The solid formed was filtered, washed
well with cold water, dried, and crystallized. In analogy, 1b,c reacted
with 2 (4 mmol each) under the same reaction conditions to give the
corresponding 5b,c 12b,c, and pyrazolone 10. The reactions were mon-
itored by tlc using toluene/ethyl acetate (3:1, v : v).
4
-Phenyl-3-methyl-1-phenylpyrazolo[3,4-b][1,5]benzothiaze-
◦
1
pine (5a): m.p.: 325 C (MeOH). Yield: 55%. H NMR: 2.1(s, 3H, CH3),
7
1
.1–7.9 (m, 14H, Ar-H). 13C NMR: 14.20 (CH3), 117.2–128.3 (benzene),
+
38.5 (C-3), 140.5 (C-4), 148.4 (C-10a). MS, m/e = 369 (M , 80%). Anal
Calcd. for C23H19N3S (369.49): C, 74.77; H, 5.18; N, 11.37. S, 8.68.
Found: C, 74.87; H, 5.10; N, 11.30; S, 8.49.
4
-(4-Nitrophenyl)-3-methyl-1-phenylpyrazolo[3,4-b][1,5]ben-
◦
1
zothiazepine (5b): m.p.: 235 C (EtOH). Yield: 45%. H NMR: 2.11 (s,
3
(
6
1
H, CH3), 7.0–7.8 (m, 13H, Ar-H). 13C NMR: 14.21 (CH3), 118.1–129.3
+
benzene), 138.9 (C-3), 141.5 (C-4), 148.8 (C-10a). MS: m/e = 414 (M ,
5%). Anal Calcd. for C23H18N4O2S (414.48): C, 66.65; H, 4.38; N,
3.52. S, 7.73. Found: C, 66.77; H, 4.10; N, 13.30; S, 7.59.
4
-(4-Chlorophenyl)-3-methyl-1-phenylpyrazolo[3,4-b][1,5]-
◦
1
benzothiazepine (5c): m.p.: 298 C (MeOH). Yield: 50%. H NMR:
.10 (s, 3H, CH3), 7.0–7.9 (m, 13H, Ar-H). C NMR: 14.12 (CH3),
17.2–129.4 (benzene), 138.2 (C-3), 141.5 (C-4), 148.9 (C-10a). MS:
1
3
2
1
m/e = 404 (M + 1, 75%). Anal Calcd. for C23H18ClN3S (403.93):
C, 68.37; H, 4.49; N, 10.40. S, 7.94. Found: C, 68.57; H, 4.30; N, 10.30;
S, 7.79.

Thiazepine Derivatives
219
1
◦
2
-Phenylbenzothiazole (12a): m.p.: 110 C (EtOH). Yield: 25%. H
+
NMR: (CDCl3, δ = ppm): 7.0–7.9 (m, 9H, Ar-H). MS; m/e = 211 (M ,
9
0%). Anal Calcd. for C13H9NS (211.28): C, 73.90; H, 4.29; N, 6.63. S,
1
5.17. Found: C, 73.72; H,4.38; N, 6.53; S, 15.10.
◦
2
-(4-Nitrophenyl)benzothiazole (12b): m.p.: 105 C (EtOH).
1
Yield: 15%. H NMR: (CDCl3, δ = ppm): 7.0–7.9 (m, 8H, Ar-H). MS;
m/e = 257 (M + 1, 85%). Anal. Calcd. for C13H8N2O2S (256.28): C,
6
0.93; H, 3.15; N, 10.93. S, 12.51. Found: C, 60.99; H, 3.25; N, 10.73; S,
1
2.75.
◦
2-(4-Chlorophenyl)benzothiazole (12c): m.p.: 220 C (EtOH).
1
Yield: 20%. H NMR: (CDCl3, δ = ppm): 7.1–7.9 (m, 8H, Ar-H). MS;
m/e = 246 (M + 1, 90%). Anal Calcd. for C13H8NclS (245.73): C, 63.54;
H, 3.28; N, 5.70. S, 13.05. Found: C, 63.82; H, 3.15; N, 5.53; S, 12.99.
REFERENCES
[
1] F. M. Abd El Latif, E. A. El-Rady, M. A. Khalil, and M. A. El-Maghraby, J. Hetero-
cyclic Chem., 39, 299 (2002).
[2] E. A. El-Rady, J. Heterocyclic Chem., 39, 1109 (2002).
[3] F. M. Abd El Latif, J. Heterocyclic Chemistry, 37, 1659 (2000).
[4] F. M. Abd El Latif, Phosphorus, Sulfur, Silicon, 167, 267 (2000).
[5] C. M. Teresa, C. Cenzo, O. Valentina, B. A. Maria, and P. Pierpaslo, J. Heterocyclic.
Chem., 34, 1347 (1997).
[
[
[
[
6] D. Ali, B. Besher, Y. Fathy, and F. Rida, Z. Naturforsch. B: Chem. Sci., 47(3), 418
(
1992).
7] A. R. Katritzky, B. V. Rogovoy, C. Chassaing, et al., J. Heterocyclic Chem., 37, 1655
2000).
8] A. Sharma, S. Pant, C. K. Sharma, and C. Umesh, Phosphorus, Sulfur, Silicon, 117,
21 (1996).
9] C. Y. Fiakpui, O. A. Phillips, K. S. K. Murthy, and E. E. Knaus, J. Heterocyclic Chem.,
6, 377 (1999).
10] S. Vega, J. A. Diaz, V. Darias, and C. C. Sanchez Mateo, J. Heterocyclic Chem., 37,
89 (2000).
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