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Synthesis and Characterization of Novel Thiazole Anchored Pyrazolyl Benzoxazoles

H. N. Akolkar and B. K. Karale*

P. G. Department of Chemistry, Radhabai Kale Mahila Mahavidyalaya, Ahmednagar, 414001, India

DOI : http://dx.doi.org/10.13005/ojc/310151

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Article Published : 12 Mar 2015
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ABSTRACT:

3-Formylchromone 1 was treated with 1-(4-(4-bromophenyl)thiazol-2-yl)hydrazine 2 to get (1-(4-(4-bromophenyl)thiazol-2-yl)-1H-pyrazol-4-yl)(2-hydroxyphenyl)methanone ­­­­­­­­(3a-e). Compound 3 on treatment with NH2OH/HCl gavethe compound 2-[(E)-{1-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-1H-pyrazol-4-yl}(hydroxyimino)methyl]phenol (4a-e). Compound 4 on treatment with POCl3 gave 2-(1-(4-(4-bromophenyl)thiazol-2-yl)-1H-pyrazol-4-yl)benzo[d]oxazole (5a-e). The synthesized compounds have been characterized with the help of spectral techniques.

KEYWORDS:

Benzo[d]oxazole; Thiazole; Pyrazole; 3-Formylchromone

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Akolkar H. N, Karale B. K. Synthesis and Characterization of Novel Thiazole Anchored Pyrazolyl Benzoxazoles. Orient J Chem 2015;31(1).


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Akolkar H. N, Karale B. K. Synthesis and Characterization of Novel Thiazole Anchored Pyrazolyl Benzoxazoles. Orient J Chem 2015;31(1). Available from: http://www.orientjchem.org/?p=7622


Introduction

Heterocyclic compounds are pharmacologically and medicinally very important because most of the drugs present in the market today are containing heterocyclic scaffolds. Benzoxazole derivatives exhibits anthelmintic1, antiulcer2, antitumor3, antimicrobial4,5andanticancer6 activities. Benzoxazole containing compounds are also acts as RSK2 inhibitor7 and α1-AR antagonist8.

Thiazole scaffold containing compounds are associated with anti-inflammatory9, cyclooxygenase-2 inhibitor10, analgesic11,monoamine oxidases12 and immunosuppressive13 activities. Pyrazole is one of the most important pharmacologically active heterocyclic compound. Pyrazole and its derivatives are associated with fungicidal14, anti-angiogenic15, antidiabetic16, antiparasitic17, antitubercular18, antimicrobial19 and antioxidant19 activities.

3-For mylchromoneis one of the class of chromone family. Chromone derivatives are known to have acetylcholinesterase inhibitor20,antitumor21, breast cancer resistance protein ABCG2 inhibition22activities.

The various pharmacological activities associated with benzoxazole, thiazole and pyrazole prompted us to synthesizesome novel thiazole anchored pyrazolyl benzoxazole  derivatives.

Experimental Section

(1-(4-(4-Bromophenyl)thiazol-2-yl)-1H-pyrazol-4-yl)(2-hydroxyphenyl)methanone 3a-e.

3-Formylchromone 1 (0.012 mol) was dissolved in 25 mL of ethanol with thiazolyl hydrazine 2 (0.012 mol). The reaction mixture heated under reflux for 40 min to get corresponding hydrazone. To the same reaction mixture 1.2 g KOH in 10 mL H2O was added and heating was continued for 4 hr. After completion of reaction the contents were cooled to room temperature and poured into crushed ice. The resulting solution was neutralized with conc. HCl. The solid obtained was separated by filtration and crystallized from ethanol to afford compound 3.

3a

IR (KBr):3085 (O-H), 1656 (C=O), 1612 (C=N), 1109 (Ar-Cl), 1218 (C-O) cm-1; 1H NMR (DMSO-d6): δ 7.40-7.82 (m, 7H, Ar-H), 8.21 & 8.97 (s, 2H, Pyrazole), 12.40 (s, 1H, O-H); MS: m/z:[M+] 493;Elem. Anal. Calcd.: C, 46.09; H, 2.04; N, 8.49; found: C, 46.12; H, 2.08; N, 8.53 %.

2-[(E)-{1-[4-(4-Bromophenyl)-1,3-thiazol-2-yl]-1H-pyrazol-4-yl}(hydroxyimino)methyl]phenol 4a-e:

Compound 3 (0.055 mol) was dissolved in 20 mL of ethanol in 150 mL conical flask. To this 10 mL of 20% KOH was added with constant stirring at 40C, and to this hydroxylamine hydrochloride (1.1 mol) was added in portion wise. Further stirring was continued for 3-4 h at room temperature. Then reaction mixture was poured into crushed ice and acidified with acetic acid. The product obtained was separated by filtration and crystallized from ethanol to afford compound 4.

4a

IR (KBr): 3185 (OH), 1630 (C=N), 1113 (Ar-Cl) cm-1; 1H NMR (DMSO-d6): 7.27-7.97 (m, 7H, Ar-H), 8.05-8.89 (s, 2H, pyrazole), 9.90 (s, 1H, -OH of oxime), 11.97 (s,1H, Ar-OH); MS: m/z:[M+] 508;Elem. Anal. Calcd.: C, 44.73; H, 2.17; N, 10.98; found: C, 44.77; H, 2.21; N, 11.02 %.

Table-1: Characterization data of synthesized compounds

Compd

R1

R2

R3

M.P.

(0C)

Yield (%)

3a

Cl

H

Cl

202

69

3b

H

Me

Cl

248

64

3c

H

H

Cl

208

67

3d

H

H

Br

205

61

3e

H

H

Me

196

59

4a

Cl

H

Cl

256

57

4b

H

Me

Cl

254

60

4c

H

H

Cl

244

53

4d

H

H

Br

222

58

4e

H

H

Me

204

48

5a

Cl

H

Cl

268

51

5b

H

Me

Cl

290

57

5c

H

H

Cl

240

55

5d

H

H

Br

250

59

5e

H

H

Me

232

46

2-(1-(4-(4-Bromophenyl)thiazol-2-yl)-1H-pyrazol-4-yl)benzo[d]oxazole 5a-e:

Compound 4 (0.055 mol) were dissolved in 15 mL of POCl3 in 50 mL RBF and the contents were heated under reflux for 2.5 h. After completion of reaction the contents were cooled to room temperature and poured into crushed ice, and neutralized by adding sodium acetate. The solid thus obtained was separated by filtration and crystallized from ethanol gave compound 5.

Scheme 1 Scheme 1 

Click here to View Scheme

 

5a

IR (KBr): 1586&1539 (C=N), 1239 (C-OC), 1114 (Ar-Cl) cm-1; 1H NMR (DMSO-d6): δ 7.35-7.83 (m, 7H, Ar-H), 8.36&9.11 (s, 2H, Pyrazole); MS: m/z:[M+] 490;Elem. Anal. Calcd.: C, 46.37; H, 1.84; N, 11.38; found: C, 46.41; H, 1.88; N, 11.42 %.

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