Synthesis of some N1-(3-hydroxy-2-pyridyl)benzamides

Article abstract of DOI:10.1080/10426500500270032

Benzoxazoles are of special interest because of having various types of biological properties such as antihistaminic, antihelmintic antifungal and antibacterial activities.^1-10 Benzamide derivatives, as the possible metabolites of benzoxazoles,

Full text of DOI:10.1080/10426500500270032

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Phosphorus, Sulfur, and Silicon
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Synthesis of Some N1-(3-
Hydroxy-2-pyridyl)benzamides
A. Mobinikhaledi a , N. Foroughifar a & M. Fallah a
a Department of Chemistry , University of Arak ,
Arak, Iran
Published online: 15 Aug 2006.
To cite this article: A. Mobinikhaledi , N. Foroughifar & M. Fallah (2006) Synthesis of
Some N1-(3-Hydroxy-2-pyridyl)benzamides, Phosphorus, Sulfur, and Silicon and the
Related Elements, 181:4, 717-721, DOI: 10.1080/10426500500270032
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Phosphorus, Sulfur, and Silicon, 181:717–721, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500270032
Synthesis of Some N1-(3-Hydroxy-2-pyridyl)benzamides
A. Mobinikhaledi
N. Foroughifar
M. Fallah
Department of Chemistry, University of Arak, Arak, Iran
Benzoxazoles are of special interest because of having various types of biolog-
ical properties such as antihistaminic, antihelmintic antifungal and antibacte-
rial activities.1−10 Benzamide derivatives, as the possible metabolites of benzox-
azoles, show various types of biological activities.11,12 Some N-(2-hydroxyphenyl)-
benzamides, which showed significant activity compared to phenylacetamides and
furamides,11 have been synthesized by treating 2-aminophenol with carboxylic acid
chlorides under weak basic solution.11,12 However, synthesis and especially biolog-
ical activity of N-(3-hydroxy-2-pyridyl)benzamides were not studied well. Owing to
the versatility of benzamides we have extended the reaction of 2-amino-3-pyridinol
with different carboxylic acid chlorides in order to preparation of some new benza-
mide derivatives containing a hydroxypyridyl ring.
Keywords 2-Amino-3-pyridinol; 3-hydroxy-2-pyridyl; benzamide
INTRODUCTION
Benzamide derivatives are of special interest because of biological prop-
erties such as antihistaminic, antihelmintic, antifungal, and antibac-
terial activities.1−12 Several article have reported biological activities
of some N-(2-hydroxyphenyl) benzamides, phenylacetamides, and fu-
ramides. N-(2-hydroxyphenyl)benzamides, which showed significant
activity compared to phenylacetamides and a furamides,10 have been
synthesized by treating 2-aminophenol with carboxylic acid chlorides
under a weak basic solution. However, the synthesis and especially the
biological activity of N-(3-hydroxy-2-pyridyl)benzamides were not stud-
ied well. Owing to the versatility of benzamides, we have extended the
reaction of 2-amino-3-pyridinol with different carboxylic acid chlorides
Received May 19, 2005; accepted May 24, 2005.
Address correspondence to A. Mobinikhaledi, Department of Chemistry, Faculty of
Science, University of Arak, Dr. Beheshti Avenue, Arak, Iran. E-mail: akbar mobini@
yahoo.com
717

718
A. Mobinikhaledi et al.
in order to prepare some new benzamide derivatives containing a hy-
droxypyridyl ring.
RESULTS AND DISCUSSION
The reaction of carboxylic acids and thionyl chloride in benzene gave the
related acid chlorides. A further reaction of the acid chlorides with 2-
amino-3-pyridinol afforded N1-(3-hydroxy-2-pyridyl)benzamides 3(a–i)
as shown in Scheme 1.
SCHEME 1
1
The HNMR spectra of the synthesized compounds are simple and
consist of the aromatic protons signals and two OH and NH proton sig-
nals. The aromatic protons including pyridine ring protons resonate as
a multiple signal at 7.10–8.35 ppm depending on the Ar group. How-
ever, the 1HNMR spectra of 3b, 3c, 3d, and 3f show a singlet signal in
the aliphatic region due to the resonance of the CH3 or OCH3 group.
On the basis of 1H NMR spectra, the structures of 3(a–i) are obtained
as a result of the nucleophilic attack on the NH2 group. In the 1HNMR
spectra of these compounds, the OH and the NH protons resonate as a
broad singlet signal at a lower chemical shift as compared to those of
the starting material. This is in support of a nucleophilic attack on the
NH2 group.
The IR spectra of 3(a–i) display two absorption bands at 1606–
11720 cm−1 and 3200–3502 cm−1, which are assigned to carbonyl and
NH groups, respectively, and are in support of the expected reactions.

1
Synthesis of Some N -(3-Hydroxy-2-pyridyl)benzamides
719
EXPERIMENTAL
Melting points were determined with an elctrothermal digital melting
point apparatus. IR spectra were taken on a Galaxy series FT-IR 5000
spectrophotometer in potassium bromide pellets. 1H NMR spectra were
recorded at 25◦C on Bruker 500 MHz spectrometers using Me4Si (TMS)
as an internal standard. Reaction courses and product mixtures were
monitored by Thin Layer Chromatography (TLC).
General Procedure for the Synthesis of
N1-(3-Hydroxy-2-pyridyl)benzamides 3(a–i)
Appropriate aromatic carboxylic acid (1 mmol) and thionyl chloride
(5 mL) were refluxed for 1–2 h. After the completion of the reaction
as monitored by TLC, the reaction mixture was cooled and the excess
amount of thionyl chloride evaporated under reduced pressure to give
the desired acid chloride. The prepared acid chloride was dissolved in
ether (10 mL) and the solution was added dropwise for 1 h to a stirred,
ice-cold mixture of 2-amino-3-pyridinol (1 mmol), sodium bicarbonate
(1 mmol), diethyl ether (10 mL) and water (10 mL). The mixture was
then stirred overnight at r.t. and flittered. The crude product was pre-
cipitated out from the filtrate, which recrystallized from a mixture of
water and ethanol.
N1-(3-Hydroxy-2-pyridyl)benzamide (3a)
Yield 40%, m.p. 95–97◦C.
IR (KBr): υ = 3200, 1630, 1590, 1100 cm−1
.
1HNMR (DMSO-d6): δ = 7.49–7.96 (m, 8H, Ar-H), 11.05 (bs, 1H, OH),
12.95 (bs, 1H, NH).
Anal. calcd. for C12H10N2O2: C, 67.2; H, 4.67; N, 13.07%. Found: C,
67.50; H, 4.53; N, 13.01%.
N1-(3-Hydroxy-2-pyridyl)-2-methylbenzamide (3b)
Yield 50%, m.p. 104–106◦C.
IR (KBr): υ = 3259, 3159, 2659, 1692, 1575, 1067 cm−1
.
1HNMR (DMSO-d6): δ = 2.49 (s, 3H, CH3), 7.28–7.82 (m, 7H) 8.10 (bs,
1H, OH), 8.30 (bs, 1H, NH).
Anal. calcd. for C13H12N2O2: C, 68.35; H, 5.26; N, 12.27%. Found: C,
68.53; H, 5.03; N, 11.95%.
N1-(3-Hydroxy-2-pyridyl)-3-methylbenzamide (3c)
Yield 55%, m.p. 120–121◦C.
IR (KBr): υ = 3502, 2970, 1687, 1589, 1215 cm−1
.

720
A. Mobinikhaledi et al.
1HNMR (DMSO-d6): δ = 2.35 (s, 3H), 7.35–7.76 (m, 7H, Ar-H), 10.20
(bs, 1H, OH), 12.20 (bs, 1H, NH).
Anal. calcd. for C13 H12N2O2: C, 68.35; H, 5.26; N, 12.27%. Found: C,
68.45; H, 5.14; N, 12.10%.
N1-(3-Hydroxy-2-pyridyl)-4-methylbenzamide (3d)
Yield 50%, m.p. 122–123◦C.
IR (KBr): υ = 3400, 3202, 1606, 1600, 1070 cm−1
.
1HNMR (DMSO-d6): δ = 2.42 (s, 3H), 7.24–7.47 (m, 7H, Ar-H), 9.98 (bs,
1H, OH), 10.65 (bs, 1H, NH).
Anal. calcd. for C13H12 N2O2: C, 68.35; H, 5.26; N, 12.27%. Found: C,
68.10; H, 5.43; N, 12.44.
N1-(3-Hydroxy-2-pyridyl)-3-nitrobenzamide (3e)
Yield 60%, m.p. 183–184◦C.
IR (KBr): υ = 3300, 3100, 1680, 1630, 1010 cm−1
.
1HNMR (DMSO-d6): δ = 7.23–7.34 (m, 4H, Ar-H), 7.95–8.35 (m, 3H,
Ar-H), 10.00 (bs, 1H, OH), 10.95 (bs, 1H, NH).
Anal. calcd. for C12H9N3O4: C, 55.56; H, 3.47; N, 16.20%. Found: C,
55.24; H, 3.10; N, 15.93%.
N1-(3-Hydroxy-2-pyridyl)-4-methoxybenzamide (3f)
Yield 50%, m.p. 123–125◦C.
IR (KBr): υ = 3481, 3174, 2947, 1720, 1606, 1078 cm−1
.
1HNMR (DMSO-d6): δ = 3.80 (s, 3H), 7.10–7.12 (m, 7H, Ar-H), 10.00
(bs, 1H, OH), 10.60 (bs, 1H, NH).
Anal. calcd. for C13H12N2O3: C, 63.87; H, 4.91; N, 11.46%. Found: C,
64.15; H, 4.71; N, 11.61%.
N1-(3-Hydroxy-2-pyridyl)-2-chlorobenzamide (3g)
Yield 40%, m.p. 142–144◦C.
IR (KBr): υ = 3459, 3359, 1667, 1473, 1051 cm−1
.
1HNMR (DMSO-d6): δ = 7.40–7.79 (m, 7H, Ar-H), 11.20 (bs, 1H, OH),
13.30 (bs, 1H, NH).
Anal. calcd. for C12H9ClN2O2: C, 57.90; H, 3.62; N, 11.26%. Found: C,
57.73; H, 3.40; N, 11.53%.
N1-(3-Hydroxy-2-pyridyl)-4-chlorobenzamide (3h)
Yield 55%, m.p. 119–120◦C.
IR (KBr): υ = 3440, 3160, 1720, 1620 cm−1
.

1
Synthesis of Some N -(3-Hydroxy-2-pyridyl)benzamides
721
1HNMR (DMSO-d6): δ = 7.5–8.20 (m, 7H, Ar-H), 8.90 (bs, 1H, OH), 10.90
(bs, 1H, NH).
Anal. calcd. for C12H9ClN2O2: C, 57.90; H, 3.62; N, 11.26%. Found: C,
57.98; H, 3.36; N, 11.49%.
N1-(3-Hydroxy-2-pyridyl)-4-bromobenzamide (3i)
Yield 40%, m.p. 243–245◦C.
IR (KBr): υ = 3270, 2910, 1690, 1587, 1012 cm−1
.
1HNMR (DMSO-d6): δ = 7.71–8.35 (m, 7H, Ar-H) 11.40 (bs, 1H,OH),
13.40 (bs, 1H, NH).
Anal. calcd. for C12H9BrN2O2: C, 49.13; H, 3.07; N, 9.55%. Found: C,
49.36; H, 3.19; N, 9.77%.
REFERENCES
[1] T. Hisano, M. Ichikawa, K. Tsumoto, and M. Tasaki, Chem. Pharm. Bull., 30, 2996
(1982).
[2] M. Prudhomme, J. Guyot, and G. Jeminet, J. Antibiotics, 39, 934 (1986).
¨
[3] S. Ersan, S. Nacak, R. Berkem, and T. Ozden, Arzneim. Forsch., 47, 963 (1997).
˙
¨
˙ ¨
[4] E. Sener, I. Yalcın, O. Temeiz, I. Oren, A. Akın, and N. Ucartu¨rk, Farmaco, 52, 99
(1997).
˙
¨
¨
˙
[5] I. Oren, O. Temiz, I. Yalcın, E. Sener, Akın, and N. Ucartu¨rk, Forsch., 47, 1393
(1997).
¨
˙
¨
˙
[6] O. Temiz, I. Oren, E. Sener, I. Yalcın, and N. Ucartu¨rk, Farmaco, 53, 337 (1998).
˙
¨
˙ ¨
˙ ¨
¨
[7] I. Yalcın, I. Oren, E. Sener, A. Akın, and N. Ucartu¨rk, J. Med. Chem., 27, 401 (1992).
[8] O. Temiz, I. Oren, and N. Altanlar, Farmaco, 57, 175 (2002).
˙
[9] E. Sener, O. Temeiz, I. Yalcın, and N. Altanlar, Farmaco, 55, 397 (2000).
˙
¨
¨
˙
[10] I. Oren, O. Temiz, I. Yalcın, E. Sener, and N. Altanlar, Eur. J. Pharm. Sci., 7, 153
(1998).
˙
¨
¨
˙
[11] E. Sener, K. Bingo¨l, I. Oren, O. Arpacı, K. I. Yalcın, and N. Altanlar, Farmaco, 55,
469 (2000).
˙
[12] E. Sener, K. I. Yalcın, and N. Altanlar, Farmaco, 57, 451 (2002).