J. Atoms and Molecules / 2(5); 2012 / 356–360 Tejas Vyas et al

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Research Article

Journal of Atoms and Molecules An International Online JournalAn International Online JournalAn International Online JournalAn International Online Journal ISSN ISSN ISSN ISSN –––– 2277 2277 2277 2277 –––– 1247124712471247

SYNTHESIS AND CHARACTERIZATION OF VARIOUS 3-[3,5-BI S (TRIFLUOROMETHYL)PHENYL]-5-(SUBSTITUTED PHENYL)-1,2 -ISOXAZOLE

Tejas Vyas1*, Kiran Nimavat 2, Kartik Vyas 3

1Research Scholar JJT University, Rajasthan, India 2 Govt. Science College, Gandhinagar 3 Sheth L.H. Science College, Mansa

Received on: 28-09-2012 Revised on: 08-10-2012 Accepted on: 18–10–2012

Abstract:

Some novel heterocyclic compounds containing isoxazole ring systems were prepared from various

chalcones. The synthesized compounds have been characterized by elemental analysis and spectral

methods

Key Words: Isooxazole; 3-[3,5-bis(trifluoromethyl)phenyl]-5-(Substituted phenyl)-1,2-isoxazole;

Hydroxyl amine hydrochloride, isooxazole compounds

Introduction:

Chalcones are synthesized by condensing

ketones with aromatic aldehydes in the

presence of suitable bases. They are very

useful intermediates for the synthesis of

five[1,2], six- [1,3] and seven-membered [4]

heterocyclic compounds. Chalcone

derivatives exhibit diverse pharmacological

activities [5-14]. It is therefore, not surprising

that many synthetic methods have been

developed for the preparation of heterocycles

starting from chalcone precursors that have

been tested for their antimicrobial activities.

* Corresponding author

Tejas Vyas,

Email: tv71104@yahoo.com Tel: +91 – 9879104795

J. Atoms and Molecules / 2(5); 2012 / 356–360 Tejas Vyas et al

All rights reserved© 2011 www.jamonline.in 357

Earlier we have reported Synthesis of novel 4-

[3,5-bis(trifluoromethyl)phenyl]-6

(Substituted phenyl)-1,6-dihydropyrimidine-

2-thiol[15].

Synthesis and Characterization of novel 6-

[3,5-bis(trifluoromethyl)phenyl]-4-

(substitutedphenyl)-1,4-dihydropyrimidin-2-

ol[16].

Synthesis, characterization and biological

screening of novel (E)-1- (3,5-

bis(trifluoromethyl)phenyl)-3-

(substituted)phenylprop-2-en-1-one[17].

In the present communication we wish to

report the reaction of various novel

halosubstituted chalcones with hydroxyl

amine hydrochloride. The structures of the

various synthesized compounds were assigned

on the basis of IR, 1H-NMR spectral data and

elemental analysis. These compounds were

also screened for their antimicrobial activity.

Materials and methods:

The solvents and reagents used in the

synthetic work were of analytical grade

obtained from Hi-media and were purified by

distillation or crystallization where necessary

and their boiling or melting points were

compared with the available literature values.

Melting points were determined in open

capillaries and are uncorrected. IR spectra

were recorded FTIR Unicorn Maltson 1000

spectrophotometer.1H-NMR spectra were

recorded on Bruker Ac-80 (80 MHz)

spectrometer (300MHz in DMSO-d6 ) using

TMS as internal standard and chemical shifts

are indicated in δ (ppm). The progress of the

reaction was monitored on precoated silica gel

60 F 254 plates (Merck) using different

solvent systems and visualizing the spots

under ultraviolet light and iodine chamber.

Elemental analyses for C, H and N were

carried out using a Perkin -Elmer C, H, and N

analyzer.

Method for Synthesis of novel 3-[3,5-

bis(trifluoromethyl)phenyl]-5-(Substituted

phenyl)-1,2-isoxazole: A mixture of (2E)-1-

[3,5-bis(trifluoromethyl)phenyl]-3-(2-

methoxyphenyl)prop-2-en-1-one, (0.02 mol),

hydroxylamine hydrochloride(0.02 mol) and

sodium acetate in ethanol (25 ml) was

refluxed for 6hr. The mixture was

concentrated by distilling out the solvent

under reduced pressure and poured into ice

water. The precipitate obtained was filtered,

washed and recrystallized. The completion of

the reaction was monitored by TLC.

All the above compounds were purified by

means of silica gel column and confirmed by

1H NMR and 13C NMR, IR, Mass and

Elemental analysis.

(2a). 3-[3,5-bis(trifluoromethyl)phenyl]-5-

(2-Methoxy phenyl)-1,2-isoxazole

MS; m/z 387; mp 278oC; Anal. Calcd. For

C18H11F6NO2; C, 55.82; H, 2.86; F, 29.43; N,

3.62; O, 8.26; Found; C, 55.76; H, 2.73; F,

29.39; N, 3.57; O, 8.22; IR (cm-1): 3049 (C-H

stretching of aromatic ring), 1703 (C=O

J. Atoms and Molecules / 2(5); 2012 / 356–360 Tejas Vyas et al

All rights reserved© 2011 www.jamonline.in 358

stretching ), 1681, 1585 and 1531 (C=C

stretching of aromatic ring), 1240 (N-O

stretching ), 1084 (C-H in plane deformation

of aromatic ring), 1012 (C-F stretching), 829

(C-H out of plane bending of 1,4-

disubutituion); 1H NMR (DMSO-d6) ppm:

6.7 to 6.9 (m, 4H aromatic), 3.86 (s, 3H, -

OCH3), 7.52-7.58 (m, 3H aromatic

fluorinated ring).

Similarly remaining compounds were

confirmed by element analysis and their mass

spectra.

(2b). 3-[3,5-bis(trifluoromethyl)phenyl]-5-

(2-Chloro phenyl)-isoxazole

MS; m/z 391; Anal. Calcd. For

C17H8ClF6NO; C, 52.13; H, 2.06; Cl, 9.05; F,

29.10; N, 3.58; O, 4.08; Found; C, 52.08; H,

2.04; Cl, 9.01; F, 29.01; N, 3.43; O, 4.01.

(2c). 3-[3,5-bis(trifluoromethyl)phenyl]-5-

(2-Fluoro phenyl)-isoxazole

MS; m/z 375; Anal. Calcd. For C17H8F7NO;

C, 54.41; H, 2.15; F, 35.44; N, 3.73; O, 4.26;

Found; C, 54.31; H, 2.06; F, 35.37; N, 3.63;

O, 4.15.

(2d). 3-[3,5-bis(trifluoromethyl)phenyl]-5-

(2-Bromo phenyl)-isoxazole

MS; m/z 436; Anal. Calcd. For

C17H8BrF6NO; C, 46.82; H, 1.85; Br, 18.32;

F, 26.14; N, 3.21; O, 3.67; Found; C, 46.71;

H, 1.67; Br, 18.21; F, 26.05; N, 3.11; O, 3.54.

(2e). 3-[3,5-bis(trifluoromethyl)phenyl]-5-

(3-Chloro phenyl)-isoxazole

MS; m/z 391; Anal. Calcd. For

C17H8ClF6NO; C, 52.13; H, 2.06; Cl, 9.05; F,

29.10; N, 3.58; O, 4.08; Found; C, 52.02; H,

2.02; Cl, 9.01; F, 29.04; N, 3.49; O, 4.01.

(2f). 3-[3,5-bis(trifluoromethyl)phenyl]-5-

(3-Methoxy phenyl)-isoxazole

MS; m/z 387; Anal. Calcd. For C18H11F6NO2;

C, 55.86; H, 2.86; Cl, 29.43; N, 3.62; O, 8.26;

Found; C, 55.76; H, 2.72; F, 29.32; N, 3.54;

O, 8.12.

(2g). 3-[3,5-bis(trifluoromethyl)phenyl]-5-

(3,4 Dimethoxy phenyl)-isoxazole

MS; m/z 417; Anal. Calcd. For C19H13F6NO3;

C, 54.69; H, 3.14; F, 27.32; N, 3.36; O, 11.50;

Found; C, 54.52; H, 3.07; F, 27.23; N, 3.24;

O, 11.43.

(2h). 3-[3,5-bis(trifluoromethyl)phenyl]-5-

(3,4-Dichloro phenyl)-isoxazole

MS; m/z 426; Anal. Calcd. For

C17H7Cl2F6NO; C, 47.91; H, 1.66; Cl, 16.64;

F, 26.75; N, 3.29; O, 3.75; Found; C, 47.84;

H, 1.53; Cl, 16.53; F, 26.64; N, 3.15; O, 3.65.

(2i). 3-[3,5-bis(trifluoromethyl)phenyl]-5-

(4-Chloro phenyl)-isoxazole

MS; m/z 391; Anal. Calcd. For

C17H8ClF6NO; C, 52.13; H, 2.06; Cl, 9.05; F,

29.10; N, 3.58; O, 4.08; Found; C, 52.02; H,

2.02; Cl, 9.01; F, 29.04; N, 3.49; O, 4.01.

J. Atoms and Molecules / 2(5); 2012 / 356–360 Tejas Vyas et al

All rights reserved© 2011 www.jamonline.in 359

(2j). 3-[3,5-bis(trifluoromethyl)phenyl]-5-

(4-Fluoro phenyl)-isoxazole

MS; m/z 375; Anal. Calcd. For C17H8F7NO;

C, 54.41; H, 2.15; F, 35.44; N, 3.73; O, 4.26;

Found; C, 54.31; H, 2.06; F, 35.37; N, 3.63;

O, 4.15.

(2k). 3-[3,5-bis(trifluoromethyl)phenyl]-5-

(4-Bromo phenyl)-isoxazole

MS; m/z 434; Anal. Calcd. For

C17H8BrF6NO; C, 46.82; H, 1.85; Br, 18.32;

F, 26.14; N, 3.21; O, 3.67; Found; C, 46.71;

H, 1.67; Br, 18.21; F, 26.05; N, 3.11; O, 3.54.

(2l). 3-[3,5-bis(trifluoromethyl)phenyl]-5-

(2,4-Dimethyl phenyl)-isoxazole

MS; m/z 385; Anal. Calcd. For C19H13F6NO;

C, 59.23; H, 3.40; F, 29.58; N, 3.64; O, 4.15;

Found; C, 59.15; H, 3.32; F, 29.43; N, 3.52;

O, 4.05.

All the above compounds were purified by

means of silica gel column and confirmed by

1H NMR, IR, Mass and Elemental analysis.

Antimicrobial study of the above synthesised

compound was also carried out.

Methanol

O

RCF3

CF3

CF3

CF3

N O

R

NH2OH.HCl/CH3COONa

References

1. ABD El-Latif, N.A.; AMR Abd, E.-G.E.;

Ibrahiem, A.A. Synthesis, reactions and

pharmacological screening of heterocyclic

derivatives using nicotinic acid as a

natural synthon.Monatsh. Chem. 2007,

138, 559-567.

2. Gaede, B.J.; Mcdermott, L.L. Novel

perfluoroalkyl-substituted pyrazoles.1.

hydroxypyrazoles.J. Heterocycl. Chem.

1993, 30, 49-54.

3. Shibata, K.; Katsuyama, I.; Izoe, H.;

Matsui, M.; Muramatsu, H. Synthesis of

4,6-di substituted 2-methyl pyridines and

their 3-carboxamides. J. Heterocycl.

Chem. 1993, 30, 277-281.

4. Jiaxi, X.; Wang, C.; Zhang, Q. Synthesis

of 1-3,3a,5-tetraaryl-3a,4,5,6-

tetrahydro3H-1,2,4-trizolo[4,3-a][1,5]

benzodiazepines. Heteroatom Chem.

2001, 6, 557-559.

5. Vibhute, Y.B.; Basser, M.A .Synthesis

and activities of a new series of chalcones

J. Atoms and Molecules / 2(5); 2012 / 356–360 Tejas Vyas et al

All rights reserved© 2011 www.jamonline.in 360

as anti bacterial agents. Indian J. Chem.

2003, 42B, 202-205.

6. Bhat, B.A.; Dhar, K.L.; Saxena, A.K.;

Shanmugavel, M. Synthesis and

biological evaluation of chalcones and

their derived pyrazoles as potential

cytotoxic agent. Bioorg. Med. Chem.

2005, 15, 3177-3180.

7. Michael, L.E.; David, M.S.; Prasad, S.S.

Chalcones: A new class of antimitotic

agents. J. Med.Chem. 1990, 33, 1948-

1954.

8. Kalirajan, R.; Palanivelu, M.;

Rajamanickam, V.; Vinothapooshan G.;

Andarajagopal, K.Synthesis and

biological evaluation of some heterocyclic

derivatives of chalcones. Int. J. Chem.Sci.

2007, 5, 73-78.

9. Udupi, R.H.; Bhat, R.; Krishna, K.

Synthesis and biological activity of

Mannish bases of certain 1,2-pyrazolines.

J. Heterocycl. Chem. 1998, 8, 143-146.

10. Alka, P.; Saxena, V.K. Synthesis and

antiviral activity of 4-(arylhydrazono)-3-

methyl-1-(3,5-dinitrobenzoyl)-2-

pyrazolin-5-ones. Indian J. Chem. 1987,

26B, 390-392.

11. Urmila, G.; Vineeta, S.; Vineeta, K.;

Sanjana, C. Synthesis and antifungal

activity of new fluorine containing 4-

(substituted phenylazo) pyrazoles and

isoxazoles. Indian J. Heterocycl. Chem.

2005, 14, 265-266.

12. Pandey, V.K.; Gupta, V.D.; Tiwari, D.N.

Synthesis of substituted benzoxazines as

potential antiviral agents. Indian J.

Heterocycl. Chem. 2004, 13, 399-400.

13. Clinton, R.O.; Manson, A.J.; Stonner,

F.W.; Beyler A.L.; Potts, G.O; Arnold, A.

Steroidal [3,2-c]pyrazoles. J. Am. Chem.

Soc. 1959, 81, 1513-1514.

14. Kalirajan, R.; Sivakumar, S.U.; Jubie, S.;

Gowramma B.; Suresh, B. Synthesis and

biological evaluation of some heterocyclic

derivatives of chalcones. Int. J. Chem.

Tech. Res. 2009, 1, 27-34.

15. Tejas Vyas.; Kiran Nimavat.; Kartik

Vyas.; “Synthesis of novel 4-[3,5-

bis(trifluoromethyl)phenyl]-6-(Substituted

phenyl)-1,6-dihydropyrimidine-2-thiol”

International journal for pharmaceutical

research scholars” V-1,I-2,00120,2012.

16. Tejas Vyas.; Kiran Nimavat.; Kartik

Vyas.; “Synthesis and Characterization of

novel 6-[3,5-bis(trifluoromethyl)phenyl]-

4-(substitutedphenyl)-1,4-

dihydropyrimidin-2-ol” International

journal for pharmaceutical research

scholars” V-1,I-3,00123,2012.

17. Tejas Vyas.; Kiran Nimavat.; Kartik

Vyas.; “Synthesis, characterization and

biological screening of novel (E)-1- (3,5-

bis(trifluoromethyl)phenyl)-3-

(substituted)phenylprop-2-en-1-one”, Der

Pharmacia Sinica, 2012, 3(2):266-270.