Synthesis and Evaluation of Some Novel 2-Amino-4-Aryl Thiazoles for Antitubercular Activity

Article abstract of DOI:10.1002/jhet.3098

A series of novel 2-amino-4-aryl thiazoles were synthesized from α-chloroacetophenone and thiourea at room temperature using acetone as solvent. The structures of synthesized compounds were confirmed by spectral data. All the compounds were evaluated for antitubercular activity by macro broth dilution method against Mycobacterium Tuberculosis H37Rv as standard strain. The synthesized compound displays notable antitubercular activity.

Full text of DOI:10.1002/jhet.3098

Month 2018
Synthesis and Evaluation of Some Novel 2-Amino-4-Aryl Thiazoles for
Antitubercular Activity
a
Gangadhar B. Gundlewad
and Bhagwan R. Patilb
*
aDepartment of Chemistry, Shri Shivaji College, Parbhani, Maharashtra 431401, India
bDepartment of Chemistry, Sharda Mahavidyalaya, Parbhani, Maharashtra 431401, India
*
E-mail: gbgundlewad@rediffmail.com
Received May 12, 2017
DOI 10.1002/jhet.3098
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel 2-amino-4-aryl thiazoles were synthesized from α-chloroacetophenone and thiourea at
room temperature using acetone as solvent. The structures of synthesized compounds were confirmed by
spectral data. All the compounds were evaluated for antitubercular activity by macro broth dilution method
against Mycobacterium Tuberculosis H37Rv as standard strain. The synthesized compound displays notable
antitubercular activity.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
worldwide and an estimated 1.4 million TB deaths,
additional 0.4 million deaths resulting from TB disease
among people living with HIV [21]. Currently, TB is treated
with the combination of first line antitubercular drugs like
rifampicin, isoniazid, ethambutal, and Pyrazinamide for 6 to
8 months. The organism Mycobacterium Tuberculosis
shows resistance to isoniazid and rifampicin. Totally, drug
resistant TB and possibility of infection with HIV is a
serious problem. The earlier mentioned drugs have side
effects like hepatotoxicity, breathlessness, pruritus, hyper
pigmentation nausea, vomiting, and diarrhea.
The first line antitubercular agent Pyrazinamide is a
nicotinamide analog. Pyrazinamide kill the dormant
nongrowing tubercle bacilli of low metabolism activity
when administered with isoniazid or rifampicin. This is
never used alone, because of these side effects of current
drugs and the serious threats of TB, the search of new
effective anti-TB drug against the resistant strains having
fever or no side effects has gaining more importance.
It was found that the biological activity of thiazole increases
with increase in lipophilic character of the molecule, it is an
important parameter related to membrane permeation in
biological system [22]. The halogen substituted aromatic
substituents at fourth position increases lipophilic nature. In
addition, the amino group at second position of thiazole
would be essential element for hydrogen bonding [23].
Therefore, the present study was designed to synthesize
such scaffold and to evaluate their antitubercular activity.
In recent years, the interest in synthesis of biologically
active heterocyclic compounds is greatly increased. The
heterocycles containing nitrogen and sulfur atom has
acquired more importance in medicinal chemistry. The
thiazole ring is a part of many potent biologically
active molecules such as Sulfathiazole (Antimicrobial
drug), Tiazofurin (Antineoplastics drug), and Ritonavir
(Antiretroviral drug). This class of compounds has
various medicinal applications like antibiotics [1], photo
sensitizers [2], antibacterial [3], antitubercular [4,5],
antifungal [6], anti-HIV [7], and anti-inflammatory [8].
Some thiazole derivatives have found applications in
drug development for the treatment of allergies [9],
hypertension [10], and schizophrenia [11]. Amino
thiazoles are also used as ligands of estrogen receptors [12].
Several methods for the synthesis of thiazole and its
derivatives were developed by Hantzsch, Tchernic,
Cook Helborn, Gabriel, and other groups [13,14].
Other methods developed by different workers, from
α-haloketone and thioamide using β-cyclodextrin as catalyst
[15], by the reaction of acetophenone with thiourea using
Br2/I2 as catalyst [16], from α-bromoketone, primary amine
and phenylisothiocynate in presence of catalytic amount of
triethylamine [17], 2-aminothiazole derivatives were
synthesized from α-bromoketone, thiourea catalytic amount
of ammonium chloride [18], ring expansion of
1-arylmethyl-2-(thiocynatomethyl)aziridine with an acyl
chloride in presence of TiCl4 [19].
Tuberculosis (TB) is a highly contagious infectious disease.
According to World Health Organization, one-third of world’s
population is currently infected with TB [20]. In 2015, there is
an estimated 10.4 million of new (incident) TB cases
RESULT AND DISCUSSION
The reaction of α-chloroacetophenone and thiourea in
acetone at room temperature gives 2-amino-4-arylthizole.
© 2018 Wiley Periodicals, Inc.

G. B. Gundlewad and B. R. Patil
Vol 000
Scheme 1. Synthesis of 2-amino-4-arylthiazoles (T1–T16). [Color figure can be viewed at wileyonlinelibrary.com]
Table 1
The reaction was completed within 15–34 min. After
completion of reaction, the solid so obtained was filtered,
washed with diethyl ether, neutralization of its aqueous
solution afforded 2-amino-4-arylthiazole. (Scheme 1) All
the products were confirmed by spectral analysis. IR
spectra shows absorption band at 3320–3370 cmÀ1 for
─NH stretching; 3110–3150 cmÀ1 for ─OH stretching;
2350–2370 cmÀ1 for C═N stretching; 1580–1610 cmÀ1
for C─N stretching; 1050–1070 cmÀ1 for C─S stretching;
732–750 cmÀ1 for C─S─C bending. In1HNMR, spectra
singlet δ 6.6–7.0 for C─H proton indicates formation of
thiazole ring. Mass spectra shows clear and distinct
molecular ion peak corresponding to the expected
molecular weight of compounds.
Antitubercular activity of 2-amino-4-arylthiazoles.
Sr. No
Entry
Interpretation
01
02
03
04
05
06
07
08
09
10
11
12
13
14
15
16
17
18
Pyrazinamide
ÀVe
ÀVe
ÀVe
ÀVe
ÀVe
ÀVe
ÀVe
ÀVe
ÀVe
ÀVe
ÀVe
ÀVe
ÀVe
ÀVe
ÀVe
ÀVe
ÀVe
+Ve
T1
T2
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
T13
T14
T15
Antitubercular activities of synthesized compounds
were studied by macrobroth dilution method using
Pyrazinamide (1000 μg/mL) as positive control and
M. tuberculosis H37Rv as standard strain. The results
(Table 1) show that all the compounds exhibited
T16
Growth control
Legends: +Ve = growth seen, ÀVe = no growth.
Table 2
Characterization data of 2-amino-4-arylthiazoles (T1–T16).
Entry
T1
Compound
Yield (%)a
80
MP (°C)b
Reaction time (min)
15
160
T2
77
75
142
150
20
22
T3
T4
77
81
175
132
27
17
T5
(Continues)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Synthesis and Evaluation of Some Novel 2-Amino-4-Aryl Thiazoles for
Antitubercular Activity
Table 2
(Continued)
Entry
T6
Compound
Yield (%)a
76
MP (°C)b
122
Reaction time (min)
24
T7
74
77
118
129
25
32
T8
T9
82
77
112
135
16
21
T10
T11
T12
T13
T14
73
72
79
75
130
121
116
167
24
29
20
26
T15
71
68
157
145
31
34
T16
aYields were isolated and unoptimized.
b
1 °C.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

G. B. Gundlewad and B. R. Patil
Vol 000
good activity against said strain of microorganism at
1500 μg/mL. The results can be correlated with the
antitubercular activity of reported derivatives of thiazole,
for example, 4-methyl-N-(4–0 × 0–2-phenylthiazolidin-3-
yl)-2-(pyrazine-2-yl)thaizol-5-carboxamide (MIC 30 μg/mL)
[24], 2-aminothazol-4-yl)methylester (MIC 1–10 μg/mL)
[23], Thiazole based on t-3-alkyl-r-2,C-6-diarylpiperidin-
4-one (MIC 265 μg/mL) [25], Substituted phenyl
thiazole derivatives (MIC 100 μg/mL) [26], S-derivatives
of clubbed triazolyl thiazole (MIC 332 μg/mL) [5],
and N-3-(4- (chlorophenylthiazol-2-yl)-2-(amino)methyl)-
quinazoline-4-(3H)-one (MIC 100 μg/mL) [27].
2H), 2.34 (s, 3H); M.S.–m/z À332 M+, Anal. % Calcd for
C10H9IN2OS: C, 36.16; H, 2.73; N, 8.43. Found: C,
36.11; H, 2.70; N, 8.58.
Synthesis of 2-(2-aminothiazol-4-yl)-6-iodo-4-methylphenol
(T2). White solid, IR (KBr.) cmÀ1 3320–3370 (─NH2),
3120 (─OH), 2356 (C═N), 1608 (C─N), 1051 (C─S),
749 (C─S─C Bending);1HNMR (CDCl3) δ ppm = 12.12
(s, 1H), 7.31 (d, 1H), 7.14 (d, 1H), 6.61 (s, 1H), 4.12
(s, 2H), 2.35 (s, 3H); M.S.–m/z À332 M+, Anal. % Calcd
for C10H9IN2OS: C, 36.16; H, 2.73; N, 8.43. Found: C,
36.10; H, 2.70; N, 8.57.
Synthesis of 6-(2-aminothiazol-4-yl)-2,4-diiodo-3-methylphenol
(T3). White solid, IR (KBr.) cmÀ1 3315–3350 (─NH2),
3130 (─OH), 2350 (C═N), 1600 (C─N), 1048 (C─S), 749
(C─S─C Bending);1HNMR (CDCl3) δ ppm = 12.11
(s, 1H), 7.51 (s, 1H), 6.58 (s, 1H), 4.13 (s, 2H), 2.31
(s, 3H); M.S.–m/z À457 M+, Anal. % Calcd for
C10H8I2N2OS: C, 26.22; H, 1.76; N, 6.12. Found: C, 26.25;
CONCLUSION
A series of novel 2-amino-4-aryl thiazoles were
synthesized from α-chloroacetophenone and thiourea
under mild and catalyst free condition. The structures of
compounds were confirmed by spectral analysis. These
compounds were screened for antitubercular activity by
Macro Broth dilution method using Pyrazinamide as
positive control and M. tuberculosis H37Rv as standard
strain. All the synthesized compounds inhibit growth at
1500 μg/mL concentration.
H, 1.75; N, 6.10.
Synthesis of 2-(2-aminothiazol-4-yl)-4-chloro-6-iodophenol
(T4). White solid, IR (KBr.) cmÀ1 3310–3350 (─NH2),
3120 (─OH), 2355 (C═N), 1610 (C─N), 1055 (C─S), 745
1
(C─S─C Bending); HNMR (CDCl3) δ ppm = 12.10 (s,
1H), 7.44 (d, 1H), 7.32 (d, 1H), 6.88 (s, 1H), 4.12 (s, 2H);
M.S.–m/z À351 M+, Anal. % Calcd for C9H6ClIN2OS: C,
30.66; H, 1.72; N, 7.95. Found: C, 30.60; H, 1.70; N, 7.87.
Synthesis of 4-iodo-2-methyl-6-(2-(methylamino)thiazol-4-yl)
phenol (T5). White solid, IR (KBr.) cmÀ1 3312 (─NH),
3116 (─OH), 2360 (C═N), 1604 (C─N), 1049
(C─S), 732 (C─S─C Bending); 1HNMR (CDCl3) δ
ppm = 12.17 (s, 1H), 7.66 (d, 1H), 7.33 (d, 1H), 6.67
(s, 1H), 5.15 (q, 2H), 3.04 (d, 3H), 2.22 (s, 3H); M.S.–m/z
À346 M+, Anal. % Calcd for C11H11IN2OS: C, 38.16; H,
EXPERIMENTAL
All the chemicals were of analytical grade. The melting
points were determined by open capillary methods and
are uncorrected. Synthesized compounds were purified
by simple crystallization. The purity of compound was
checked by thin-layer chromatography. The IR spectra
were recorded on “Shimadzu” IR spectrophotometer
using KBr pallet. 1HNMR spectra were recorded on
“Avance-300” spectrometer using CDCl3 as solvent and
tetramethylslane as internal standard. Mass spectra were
recorded in electron impact mode.
3.20; N, 8.09. Found: C, 37.99; H, 3.18; N, 8.01.
Synthesis of 2-iodo-4-methyl-6-(2-(methylamino)thiazol-4-yl)
phenol (T6). White solid, IR (KBr.) cmÀ1 3315 (─NH),
3110 (─OH), 2320 (C═N), 1600 (C─N), 1045 (C─S),
1
750 (C─S─C Bending); HNMR (CDCl3) δ ppm = 12.09
(s, 1H), 7.51 (d, 1H), 7.32 (d, 1H), 6.71 (s, 1H), 4.13 (q,
2H), 2.41 (d, 3H), 2.29 (s, 3H); M.S.–m/z À346 M+,
Anal. % Calcd for C11H11IN2OS: C, 38.16; H, 3.20; N,
8.09. Found: C, 37.98; H, 3.14; N, 8.01.
General procedure for the synthesis of 2-amino-4-
arylthiazole.
Corresponding α-chloroacetophenone
Synthesis of 2,4-diiodo-3-methyl-6-(2-(methylamino)thiazol-
4-yl)phenol (T7).
White solid, IR (KBr.) cmÀ1 3318
(1 mmol.) and thiourea (1 mmol.) were dissolved separately
in acetone. Both the solutions were mixed and kept at room
temperature for 15–34 min. The resulting white product
was filtered and washed with diethyl ether. Neutralization
of its aqueous solution with dilute ammonia afforded
2-amino-4-arylthiazole and recrystallization from absolute
ethanol gave analytically pure products. (Table 2).
Synthesis of 2-(2-aminothiazol-4-yl)-4-iodo-6-methylphenol
(T1). White solid, IR (KBr.) cmÀ1 3313–3370 (─NH2),
(─NH), 3100 (─OH), 2330 (C═N), 1610 (C─N), 1059
(C─S), 745 (C─S─C Bending); 1HNMR (CDCl3) δ
ppm = 12.13 (s, 1H), 7.45 (s, 1H), 6.69 (s, 1H), 4.14
(q, 2H), 2.40 (d, 3H), 2.28 (s, 3H); M.S.–m/z À472 M+,
Anal. % Calcd for C11H10I2N2OS: C, 27.99; H, 2.14; N,
5.93. Found: C, 27.80; H, 2.10; N, 5.90.
Synthesis of 4-chloro-2-iodo-6-(2-(methylamino)thiazol-4-yl)
phenol (T8). White solid, IR (KBr.) cmÀ1 3312 (─NH),
3116 (─OH), 2360 (C═N), 1604 (C─N), 1049 (C─S),
752 (C─S─C Bending); HNMR (CDCl3) δ ppm = 11.79
(s, 1H), 7.65 (d, 1H), 7.34 (d, 1H), 6.71 (s, 1H), 5.05 (s,
3150 (─OH), 2360 (C═N), 1605 (C─N), 1055
(C─S), 755 (C─S─C Bending); 1HNMR (CDCl3) δ
ppm = 12.10 (s, 1H), 7.51 (d, 1H), 7.32 (d, 1H), 6.71
1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Synthesis and Evaluation of Some Novel 2-Amino-4-Aryl Thiazoles for
Antitubercular Activity
(s, 1H), 4.20 (q, 2H), 2.45 (d, 3H); M.S.– m/z À365 M+,
Anal. % Calcd for C10H8ClIN2OS: C, 32.76; H, 2.20; N,
7.64. Found: C, 32.70; H, 2.18; N, 7.63.
ppm = 12.21 (s, 1H), 7.27 (s, 1H), 6.78 (s, 1H), 1.99
(s, 1H), 6.7–7.4 (m,7H), 2.21 (s, 3H); M.S.– m/z À484 M+,
Anal. % Calcd for C20H14I2N2OS: C, 41.12; H, 2.42; N,
4.80. Found: C, 41.11; H, 2.44; N, 4.81.
Synthesis of 4-iodo-2-methyl-6-(2-(phenylamino)thiazol-4-yl)
phenol (T9). White solid, IR (KBr.) cmÀ1 3363 (─NH),
Synthesis of 4-chloro-2-iodo-6-(2-(naphthalen-3-ylamino)
thiazol-4-yl)phenol (T16).
White solid, IR (KBr.) cmÀ1
3124 (─OH), 2360 (C═N), 1593 (C─N), 1060 (C─S), 752
1
3382 (─NH), 3119 (─OH), 2375 (C═N), 1605 (C─N),
(C─S─C Bending); HNMR (CDCl3) δ ppm = 12.26 (s,
1
1055 (C─S), 755 (C─S─C Bending); HNMR (CDCl3) δ
1H), 7.54 (d, 1H), 7.17 (q, 1H), 6.82 (s, 1H), 1.58 (s, 1H),
7.40 (t, 2H) 7.31 (q, 3H), 2.26 (s 3H); M.S.– m/z À408
M+, Anal. % Calcd for C16H13IN2OS: C, 47.07; H, 3.21;
ppm = 12.3 (s, 1H), 7.57 (d, 1H), 7.12 (d, 1H), 6.81
(s, 1H), 2.29 (s, 1H), 6.7–7.4 (m, 7H); M.S.– m/z À478
M+, Anal. % Calcd for C19H12ClIN2OS: C, 47.67; H,
2.53; N, 5.85. Found: C, 47.65; H, 2.55; N, 5.82.
N, 6.86. Found: C, 47.10; H, 3.20; N, 6.85.
Synthesis of 2-iodo-4-methyl-6-(2-(phenylamino)thiazol-4-yl)
phenol (T10). White solid, IR (KBr.) cmÀ1 3380 (─NH),
3140 (─OH), 2365 (C═N), 1600 (C─N), 1055 (C─S),
1
745 (C─S─C Bending); HNMR (CDCl3) δ ppm = 12.2
Acknowledgments. We gratefully acknowledge the Haffkine
Institute Mumbai, for providing antitubercular activity studies,
IICT Hyderabad, for providing spectral data, Principal, Shri
(s, 1H), 7.5 (d, 1H), 7.17 (d, 1H), 6.81 (s, 1H), 1.58
(s, 1H), 7.41 (t, 2H) 7.33 (q, 3H), 2.28 (s, 3H); M.S.– m/z
À408 M+, Anal. % Calcd for C16H13IN2OS: C, 47.07; H,
3.21; N, 6.86. Found: C, 47.10; H, 3.22; N, 6.84.
Shivaji College, Parbhani
&
Principal, DSM College,
Parbhani. We are thankful to UGC WRO for financial
assistance.
Synthesis of 2,4-diiodo-3-methyl-6-(2-(phenylamino)thiazol-
4-yl)phenol (T11).
White solid, IR (KBr.) cmÀ1 3370
(─NH), 3170 (─OH), 2360 (C═N), 1608 (C─N), 1057
(C─S), 755 (C─S─C Bending); 1HNMR (CDCl3) δ
ppm = 12.02 (s, 1H), 7.17 (s, 1H), 6.89 (s, 1H), 1.55
(s, 1H), 7.48 (t, 2H) 7.34 (q, 3H), 2.27 (s, 3H); M.S.– m/z
À533 M+, Anal. % Calcd for C16H12I2N2OS: C, 35.98; H,
REFERENCES AND NOTES
[1] Hoshino, K.; Ishida, H.; Omovskaya, O.; Dudley, M.; et al.
Japan KokaiTokkyoKoho CODEN; JKXXAF JP 2002322054 A2
20021108; 2002;Chem Abstr 2002, 137, 346134.
[2] Shimada, Y. Japan KokaiTokkyoKoho CODEN; JXXAF JP
02113070 A2 19900425; 1990;Chem Abstr 1990, 113, 99405.
[3] Dighe, S. N.; Chaskar, P. K.; Jain, K. S.; Phoujdar, M. S.;
Shrinivasan, K. V. ISRN Organic Chemistry 2011. https://doi.org/
10.5402/2011/434613.
[4] Karuvalam, R. P.; Haridas, K. R.; Nayak, S. K.; Guru Row, T.
N.; Rajeesh, P.; Rishikesan, R.; SuchethaKumari, N. Eur J Med Chem
2012, 49, 172.
[5] Shiradakar, M. R.; Murahari, K. K.; Gangadasu, H. R.; Suresh,
T.; Kalyan, C. A.; Panchal, D.; Kaur, R.; Burange, P. Bioorg Med Chem
2007, 15, 3997.
[6] Chimenti, F.; Bizzarri, B.; Maccioni, E.; Secci, D.; Bolosco, A.;
Fioravanti, R.; Chimenti, P.; Granese, A.; Carradori, S.; Rivanera, D.; Lilli,
D.; Zicari, A.; Distinto, S. Bioorg Med Chem Lett 2007, 17, 4635.
[7] Masuda, N.; Moritomo, A.; Yamamoto, O.; Fujji, M.; Ohgami,
T.; Kantani, T.; Ohta, S.; Kageyama, M. Synth Commun 2005, 35, 2305.
[8] Kalkhambkar, R. G.; Kulkarni, G. M.; Shivkumar, H.; Rao,
N. R. Eur J Med Chem 2007, 42, 1272.
[9] Carter, J. S.; Kramer, S.; Talley, J. J.; Penning, T.; Collins, P.;
et al. Bioorg Med Chem Lett 1999, 9, 11171.
[10] Patt, W. C.; Hamilton, H. W.; Taylor, M. D.; Ryan, M. J.; et al.
J Med Chem 1992, 35, 2562.
2.26; N, 5.24. Found: C, 36.00; H, 2.25; N, 5.25.
Synthesis of 4-chloro-2-iodo-6-(2-(phenylamino)thiazol-4-yl)
phenol (T12). White solid, IR (KBr.) cmÀ1 3360 (─NH),
3160 (─OH), 2372 (C═N), 1610 (C─N), 1049 (C─S),
1
749 (C─S─C Bending); HNMR (CDCl3) δ ppm = 12.0
(s, 1H), 7.52 (d, 1H), 7.32 (d, 1H), 6.9 (s, 1H), 1.9 (s,
1H), 7.48 (t, 2H) 7.30 (q, 3H); M.S.– m/z À428 M+,
Anal. % Calcd for C15H10ClIN2OS: C, 42.03; H, 2.35; N,
6.53. Found: C, 42.00; H, 2.36; N, 6.53.
Synthesis of 4-iodo-2-methyl-6-(2-(naphthalen-3-ylamino)
thiazol-4-yl)phenol (T13).
White solid, IR (KBr.) cmÀ1
3392 (─NH), 3120ss (─OH), 2365 (C═N), 1615 (C─N),
1
1075 (C─S), 759 (C─S─C Bending); HNMR (CDCl3) δ
ppm = 12.03 (s, 1H), 7.57 (d, 1H), 7.12 (d, 1H), 6.81 (s,
1H), 1.59 (s, 1H), 6.7–7.4 (m, 7H), 2.23 (s 3H); M.S.–
m/z À458 M+, Anal. % Calcd for C20H15IN2OS: C,
52.41; H, 3.30; N, 6.11. Found: C, 52.42; H, 3.28; N, 6.10.
Synthesis of 2-iodo-4-methyl-6-(2-(naphthalen-3-ylamino)
[11] Jaen, J. C.; Wise, l. D.; Caprathe, B. W.; Tecle, H.; Bergmeir,
S.; Humblet, C. C.; Heffner, T. G.; Meltzner, L. T.; Pugsley, T. A. J
Med Chem 1990, 33, 311.
[12] Fink, B. A.; Mortensen, D. S.; Stauter, S. R.; Aron, Z. D.;
Katzenellenbogen, J. A. Chem Biol 1999, 6, 205.
thiazol-4-yl)phenol (T14).
White solid, IR (KBr.) cmÀ1
3395 (─NH), 3170 (─OH), 2372 (C═N), 1625 (C─N),
1
1065 (C─S), 757 (C─S─C Bending); HNMR (CDCl3) δ
[13] Hantzsch, A.; Weber, J. H. Ber Dtsch Chem Ges 1887, 20,
3118.
ppm = 12.13 (s 1H), 7.58 (d 1H), 7.19 (d 1H), 6.91
(s 1H), 2.01 (s 1H), 6.7–7.4 (m 7H), 2.21 (s 3H); M.S.–
m/z À458 M+, Anal. % Calcd for C20H15IN2OS: C,
52.41; H, 3.30; N, 6.11. Found: C, 52.40; H, 3.31; N, 6.12.
Synthesis of 2,4-diiodo-3-methyl-6-(2-(naphthalen-3-ylamino)
[14] Metzger,
J.
V.
In
Comprehensive
Heterocyclic
ChemistryKatritky, R.; Rees, C. W. Eds.; Pergamon: New York, 1984;
Vol 6, pp. 235–332.
[15] Narender, M.; Somi Reddy, M.; Sridhar, R.; Nageswar, Y. V. D.;
Rama Rao, K. Tetrahedron Lett 2005, 46, 5953.
[16] Pattan, S. R.; Dighe, N. S.; Nirmal, S. A.; Merekar, A. N.;
Laware, R. B.; Shinde, H. V.; Musmande, D. S. Asian J Research Chem
2009, 2(2), 196.
thiazol-4-yl)phenol (T15).
White solid, IR (KBr.) cmÀ1
3372 (─NH), 3115 (─OH), 2371 (C═N), 1617 (C─N),
1
1088 (C─S), 769 (C─S─C Bending); HNMR (CDCl3) δ
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

G. B. Gundlewad and B. R. Patil
Vol 000
[17] Heravi, M. M.; Moghimi, S. Tetrahedron Lett 2012, 53, 392.
[18] Pagore, V. P.; Tekale, S. U.; Rupnar, B. D.; Pawar, R. Der
Chemica Sinica 2015, 6(5), 49.
[19] Dhooghe, M.; Waterniky, A.; De Kimpe, N. J. Org Chem
2005, 70, 227.
[20] http://www.who.int/tb/challenges/xdr_map08pdf
[21] http://www.who.int/tb/publications/global_report/en/
[22] Parker, M. A.; Kurrasch, D. M.; Akiba, S.; Nichols, D. E.
Bioorg Med Chem 2008, 16, 4661.
[25] Aridoss, G.; Amirthaganesan, S.; Kim, M. S.; Jeong, Y. T. Eur
J Med Chem 2009, 44, 4199.
[26] Pattan, S. R.; Bukitagar, A. A.; Pattan, J. S.; Kapadnis, B. P.;
Jadhav, S. J. IJC Sec B 2009, 48B, 1033.
[27] Pattan, S. R.; Krishna Reddy, V. V.; Manvi, F. V.; Desai, B. G.;
Bhat, A. R. IJC Sec B 2006, 45B, 1778.
[23] Karuvalam, R. P.; Haridas, K. R.; Nayak, S. K.; GuruRow, T. N.;
Rajesh, P.; Rishikesan, R.; Suchetha Kumari, N. Eur J Med Chem 2012, 49,
172.
SUPPORTING INFORMATION
Additional Supporting Information may be found online
in the supporting information tab for this article.
[24] Dhumal, S. T.; Deshmukh, A. R.; Khillare, L. D.; Arkile, M.;
Sarkar, D.; Mane, R. A. J Heterocyclic Chem 2017.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet