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    Synthesis of Novel Oxazoles and Their Hydrazones: Vijay V Dabholkar and Sagir Ahmed Sabir Ali Syed

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    Yogesh Rathi
    Oxazoles are well known as important structural units in a wide variety of biologically active natural products. The ability of a, b-unsaturated ketones to react with various nucelophilic reagents prompted us to synthesis some new fused oxazole compounds.

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    Synthesis of Novel Oxazoles and Their Hydrazones: Vijay V Dabholkar and Sagir Ahmed Sabir Ali Syed

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    Yogesh Rathi
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    Oxazoles are well known as important structural units in a wide variety of biologically active natural products. The ability of a, b-unsaturated ketones to react with various nucelophilic reagents prompted us to synthesis some new fused oxazole compounds.

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    Oxazoles are well known as important structural units in a wide variety of biologically active natural products. The ability of a, b-unsaturated ketones to react with various nucelophilic reagents prompted us to synthesis some new fused oxazole compounds.

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    52 views5 pages

    Synthesis of Novel Oxazoles and Their Hydrazones: Vijay V Dabholkar and Sagir Ahmed Sabir Ali Syed

    Uploaded by

    Yogesh Rathi
    Oxazoles are well known as important structural units in a wide variety of biologically active natural products. The ability of a, b-unsaturated ketones to react with various nucelophilic reagents prompted us to synthesis some new fused oxazole compounds.

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    Attribution Non-Commercial (BY-NC)
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    of 5

    Vol.3, No.4 (2010), 761-765 ISSN: 0974-1496 CODEN: RJCABP http://www.rasayanjournal.

    com

    SYNTHESIS OF NOVEL OXAZOLES AND THEIR HYDRAZONES


    1

    Vijay V Dabholkar1 and Sagir Ahmed Sabir Ali Syed1*


    Organic Research Laboratory, Department of Chemistry, KC College, Churchgate, Mumbai-20 Mumbai University, Maharashtra, Mumbai (India) *E-mail: [email protected]

    ABSTRACT 2, 4-disubstituted Oxazoles (2) were prepared from Hippuric acid/acetyl glycine, substituted aromatic aldehydes, acetic anhydride and sodium acetate as a catalyst. Further reacting with hydrazine hydrate yielded corresponding hydrazones (3), which on condensation reaction with different aldehydes revealed final Schiff base. The structures of the compounds have been elucidated on the basis of spectral analysis. Keywords: Hippuric acid, Acetyl glycine, Oxazoles, Hydrazones.
    2010 RASYAN. All rights reserved

    INTRODUCTION
    Substituted Oxazole derivatives are found to be associated with various biological activities such as antibacterial1, antifungal2, antitubercular3, anti-inflammatory4. Oxazoles are well known as important structural units in a wide variety of biologically active natural products as well as useful synthetic intermediates5-7. The oxazolone ring occurs naturally and the total synthesis of natural products with a wide variety of biological activities containing Oxazole moiety is an area of intense research. Other applications of Oxazole derivatives include the use as pesticides, fluorescent whitening agents, lubricants, dyes and pigments 8-16. Therefore, there is considerable interest of having available efficient routes to these heterocycles and better understand their reactivity. The ability of , -unsaturated ketones to react with various nucelophilic reagents prompted us to synthesis some new fused oxazole compounds. Schiff base of 2-methyl / phenyl -4-benzylidene -5hydrazino -1, 3-Oxazole (4) were obtained by condensing 2-methyl / phenyl-4-benzylidene-5-Oxo-1, 3Oxazole (2) with hydrazine hydrate and aromatic aldehydes (Scheme-1).

    EXPERIMENTAL
    Melting points of all synthesized compounds were determined in open capillary tubes on an electro thermal apparatus and are uncorrected. The purity of the compounds was monitored by thin layer chromatography on silica gel coated aluminium plates (Merck) as adsorbent and UV light as visualizing agent. IR spectra (KBr in cm-1) were recorded on a Perkin-Elmer spectrophotometer in the range of 4000-400 cm-1. 1H NMR spectra were recorded on a Varian 500 MHz NMR spectrometer using CDCl3/DMSO-d6 as solvent and TMS as an internal standard (chemical shifts in ppm). Synthesis of 2, 4-disubsituted-oxazoles (2) A mixture of aromatic aldehydes (0.25 moles), Hippuric acid (44.8 gm, 0.25 mole) / acetyl glycine (29 gm, 0.25 moles), anhydrous sodium acetate (15 gm), and acetic anhydride (59 ml) was heated at 110C, with constant stirring. The mixture become almost solid, and then as the temperature rises, it gradually liquefies and turns deep yellow in color. After completion of the reaction monitored by TLC the reaction is allowed to cool and ethanol (100 ml) is added slowly to the contents of the flask. After allowing the reaction mixture is left to stand overnight, the yellow color product is filtered and washed with ice cold ethanol and finally with boiling water and recrystallized in ethanol to yield 2a. 2-methyl / phenyl-4-Benzylidene-5-hydrazino-1, 3- Oxazole (3)

    NOVEL OXAZOLES AND THEIR HYDRAZONES

    V.V. Dabholkar and S. A. S.Ali Syed

    Vol.3, No.4 (2010), 761-765

    Mixture of 2 (0.05 mole), Hydrazine hydrate (0.05 mole), Methanol (10 mL) was taken in 100 mL round bottom flask and the mixture was reflux for 1 hr. After monitoring the reaction on TLC, the reaction mixture was cooled and dumped on to ice, filtered and recrystallized from ethanol to yield 3. Schiff base of 2-methyl / phenyl-4-Benzylidene-5-hydrazino-1, 3-Oxazole (4) Mixture of 3 (0.05 mole), aromatic aldehydes (0.05 mole), Potassium hydroxide (0.1 mole), Ethanol (10 mL) was taken in 100 mL round bottom flask and the mixture was reflux for 4 hrs. After monitoring the reaction on TLC, the reaction mixture cooled and dumped on to ice, filtered and recrystallized from ethanol to yield 4. The physical and characterization data of the compounds 4a-u are listed in the Tables I Antimicrobial evaluation Representative samples were screened for their antimicrobial and antifungal activity against gramnegative bacteria, E coli and P aeruginosa and gram-positive bacteria, S aureus, and C diphtheriae using disc diffusion method17, 18. The zone of inhibition was measured in mm and the activity was compared with standard drug. The results of antibacterial screening studies are reported in Table II.

    RESULTS AND DISCUSSION


    The Schiff base of 2-methyl / phenyl -4-benzylidene -5-hydrazino -1, 3-Oxazole (4) were obtained by condensation of 2-methyl / phenyl-4-benzylidene-5-Oxo-1, 3-Oxazole (2) with hydrazine hydrate followed by different aromatic aldehydes with good yield. Further, the representative compounds were screened for their antimicrobial activity against gram negative as well as gram positive bacteria, which shows convincing activity.

    ACKNOWLEDGEMENT
    The authors are grateful to the Principal Ms. Manju J. Nichani and Management of K.C. College, Mumbai for providing necessary facilities. Authors are also thankful to the Director, Institute of Science, Mumbai for providing spectral analyses.

    REFERENCES
    1. 2. 3. 4. 5. 6. 7. K. Tsuji, H. Isgikawa, Bio-org. Med. Chem. Lett, 4, 1601(1994). C. George, N. Martin, R. Ray, J. Med. Chem.16, 1402(1973). C.G.Anna, I.M.B.Helenam, G.F. Scitt, E.B.Clifton, R.C. Brent, Tetrahedron Lett, 46, 7355(2005) George, C.; Michael, J.F. J. Med. Chem.14 (1971), 1075-77. P. Wipf, Chem.Rev, 2115(1995). S. Cicchi, F.M. Cordero, D. Giomi,Prog. Heterocycl.Chem, 12, 217(2001). J.R. Lewis, Natural Product Reports, 12, 135 (1995); K.J. Doyle, C.J. Moody,Tetrahedron 50, 3761 (1994); G. Videnov, D. Kasier, G. Jung, Angew.Chem.Int. Ed.Engl., 35(13/14), 1503(1996); A.R. Katritzky, C. W. Rees, Eds.; Pergamon Press: Oxfort, Chapter 18(1984). S.A. Lang Jr., Y.l. Lin, in: A.R. Katritzky, C.W. Rees, K.T. Potts (Eds), Comprehensive Heterocyclic Chemistry, Vol. 6, Pergamon, Oxford, (1984), Chapter 4.16 and Chapter 4.18; T.M.V.D. Pinho E Melo, Curr. Org. Chem. 9, 925 (2005) V.S.C. Yeh, Tetrahedron 60 , 11995(2004) Y. Hamada, T. Shioiri, Chem. Rev. 105,4441(2005) P. Wipf, Chem. Rev. 95, 2115(1995). Vijay V. Dabholkar and Sagar D. Parab, Indian Journal of Chemistry, 46B, 344(2007). Vijay V. Dabholkar and Sushil Kumar J. Mishra, Indian Journal of Chemistry, 45B , 2112(2006). Vijay V. Dabholkar and Sushil Kumar J. Mishra, Heterocyclic Communication, 12(3-4) , 241(2006). Vijay V. Dabholkar and Ashish S. Sanghvi, Indian Journal of Heterocyclic Chemistry, 16 , 105(2006). R. Cruickshank, J.P. Duguid and B.P. Marmion, Medicinal Microbiology,12th Edn,11, 1975, (Churchill Livingstone, London). B.A. Arthington-Skaggs, M. Motley and C.J. Morrison, J. Clin. Microbiology, 38, 2254(2000).

    8. 9. 10. 11. 12. 13. 14. 15. 16. 17.

    18.

    [RJC-687/2010]
    NOVEL OXAZOLES AND THEIR HYDRAZONES

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    Vol.3, No.4 (2010), 761-765 Table-1: Characterization of synthesized Compounds 4 Spectral data IR (KBr cm-1)/1H NMR/13C NMR (ppm) in DMSO-d6 /C H and N Analysis.

    Compd

    R1

    R2

    R3

    R4

    m.p (C )

    4a

    CH3

    220-222

    IR: 3031 (CH-Str), 1664 (C=N), H NMR: 2.1 (s, 3H, CH3), 6.9- 7.7(m, 12H, ArH & CH)

    [Found : C, 74.72, H, 5.23, N, 14.52, C18H15N3O requires C, 74.70, H, 5.33, N, 14.42 %] 4b 4c 4d 4e 4f 4g 4h 4i CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 H H OCH3 OCH3 OCH3 OH OH OCH3 H H H H H H H OH OCH3 OH OCH3 OH OCH3 OCH3 OH OCH3 H H H H OH H H H 225-227 240-243 238-240 228-230 230-232 225-227 218-220 255-257 IR: 3028 (CH-Str), 1658 (C=N) IR: 3125 (OH), 3018 (CH-Str), 1664 (C=N) IR: 3031 (CH-Str), 1662 (C=N) IR: 3138 (OH), 3028 (CH-Str), 1655 (C=N) IR: 3122 (OH), 3018 (CH-Str), 1664 (C=N) IR: 3132 (OH), 3022 (CH-Str), 1652 (C=N) IR: 3128 (OH), 3025 (CH-Str), 1612 (C=N) IR: 3127 (OH), 3018 (C=CHR), 1664 (C=N), H NMR: 1.9 (s, 3H, CH3), 3.7 (s, 3H, OCH3), 3.8 (s, 3H, OCH3), 6.87.8(m, 9H, ArH & 2CH), 8.2 (br,1H,OH), [Found : C, 65.74, H, 5.24, N, 11.50, C20H19N4O3 requires C, 65.65, H, 5.15, N, 11.42 %] 4j 4k 4l 4m CH3 CH3 C6H5 C6H5 OCH3 OCH3 H H OH OH H H OH OCH3 OH OCH3 H OH H OH 230-233 218-220 255-257 248-250 763 IR: 3120 (OH), 3017 (CH-Str), 1660 (C=N) IR: 3131 (OH), 3018 (CH-Str), 1664 (C=N) IR: 3118 (OH), 3025 (CH-Str), 1652 (C=N) IR: 3142 (OH), 3030 (CH-Str), 1660 (C=N)
    V.V. Dabholkar and S. A. S.Ali Syed
    1

    NOVEL OXAZOLES AND THEIR HYDRAZONES

    Vol.3, No.4 (2010), 761-765 4n C6H5 Cl H H H 250-252 IR: 3032 (CH-Str), 1647 (C=N), 1H NMR: 7.3- 7.9 (m, 16H, ArH & 2CH) [Found : C, 71.52, H, 4.15, N, 10.86, C23H16ClN3O requires C, 71.59, H, 4.18, N, 10.89%] IR: 3129 (OH), 3027 (CH-Str), 1652 (C=N) IR: 3126 (OH), 3031 (CH-Str), 1654 (C=N) IR: 3130 (OH), 3026 (CH-Str), 1648 (C=N) IR: 3128 (OH), 3030 (CH-Str), 1642 (C=N) IR: 3138 (OH), 3027 (CH-Str), 1649 (C=N) IR: 3132 (OH), 3026 (CH-Str), 1664 (C=N), 1H NMR: 3.5 (s, 3H, OCH3), 5.5 (br,1H,OH), 6.7- 8.0(m, 14H, ArH & 2CH), 9.4(br,1H,OH), 13C NMR: 55.11(OCH3), 112.92(CH), 119.33(C=C), 125.19-133.47(Ar-C), 147.29(C=N), 147.97(C=N), 150.20(C=N). [Found : C, 69.66, H, 4.60, N, 10.12, C24H19N3O4 requires C, 69.72, H, 4.63, N, 10.16%] IR: 3125 (OH), 3030 (CH-Str), 1664 (C=N), 1H NMR: 3.6 (s, 3H, OCH3), 3.8 (s, 3H, OCH3) 6.7- 8.0(m, 13H, ArH & 2CH), 9.9(br,1H,OH), 11.3(br,1H,OH),13C NMR: 55.16(OCH3), 55.58(OCH3), 112.96(CH), 120.08(C=C), 124.18-133.88(Ar-C), 147.29(C=N), 147.86(C=N), 150.19(C=N). [Found : C, 67.68, H, 4.62, N, 9.48, C25H21N3O5 requires C, 67.71, H, 4.77, N, 9.48%]

    4o 4p 4q 4r 4s 4t

    C6H5 C6H5 C6H5 C6H5 C6H5

    OCH3 OCH3 OH OH OH

    H H H H H OH

    OH OCH3 H OCH3 Cl OH

    H OH H H H H

    268-270 257-260 255-257 270-272 247-250 245-248

    C6H5 OCH3

    4u

    C6H5 OCH3 OH

    OCH3

    OH

    238-240

    __________________________________________________________________________________________________________________________

    NOVEL OXAZOLES AND THEIR HYDRAZONES

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    Vol.3, No.4 (2010), 761-765

    Scheme-1 Table-2: Antibacterial activity of compound 4 Zone of Inhibition (in mm) Gram Negative Gram Positive S.aureus C.diphtheria P.aeruginosa E.coli 4a 8 9 12 12 4d 9 11 14 10 4e 11 8 12 12 4i 9 10 10 11 4n 8 11 11 10 4o 10 11 12 14 4q 12 10 14 12 4t 13 16 18 14 4u 14 18 18 15 Ampicillin trihydrate 26 28 24 21 DMSO 00 00 00 00 * Diameter of the disc was 6 mm, concentration of the compounds taken was about 100 g/mL. Compounds

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