SYNTHESIS OF ASPIRIN DERIVATIVES AS ANTIMICROBIAL AGENT

Introduction

• Over the centuries, many antibacterial drugs were used to treat bacterial-causing diseases including food poisoning, pneumonia and intestinal infection [Y. G¨ulkok, T. Bic¸er, F. K. Onurda˘g, S. ¨ Ozgen, M. F. S¸ahin, and D. S. Do˘gruer, 2012, E. Rubinand H.M. Reisner, Eds, 2009].
• The improper usage of these drugs has caused the bacteria to evolve into drug resistant bacteria which reduce the effectiveness of the drugs [R. Richard-Kortum, 2010].
• The continuing development of new antibacterial agents therefore remains a priority [Y. G¨ulkok, T. Bic¸er, F. K. Onurda˘g, S. ¨ Ozgen, M. F. S¸ahin, and D. S. Do˘gruer, 2012].

Objectives

• To synthesize aspirin and its halide-containing derivatives from salicylic acid halides and acetic anhydride.

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• To characterize the synthesized aspirin and its derivatives using melting point determination, Proton Nuclear Magnetic Resonance (H-NMR), Mass Spectroscopy and Fourier-Transform Infrared (FT-IR)spectroscopy.

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• To evaluate the antibacterial activity of the synthesized aspirin and its derivatives against a multi-resistant drug E.coli

Review of Related Literature

• Aspirin is a generally utilized medication for antipyretic, pain relieving, and mitigating [K. L. Williamson, 2013]. The interest of anti-inflammatory medicine and its subsidiaries for other organic properties is expanding because of its accessibility and reactivity as antecedent for additional adjustment through relating carboxyl gathering [Z. Ngaini, M. A. Moh’d Arif, H. Hussain, E. S. Mei, D.Tang, and D. H. A. Kamaluddin, 2012]. Aspirin subsidiaries have demonstrated antibacterial exercises against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa [A. Lawal and J. A. Obaleye, 2007, B. B. Chavan, P. D. Chitte, N. P. Choudhary, K. G. Albhar, and V. I. Hukkeri, 2012]. Other critical organic properties of anti-inflamatory medicine subordinates are accounted for antitumor, anticancer, antifungal, and antimicrobial specialists [Z. Ngaini, M. A. MohdArif,H.Hussain, E. S.Mei,D.Tang, and D. H. A. Kamaluddin, 2012, B. B. Chavan, P. D. Chitte, N. P. Choudhary, K. G. Albhar, and V. I. Hukkeri, 2012].

Review of Related Literature (Cont’d)

• Lawal et al. (2006) revealed that the amalgamation of anti-inflamatory medicine and paracetamol with metal edifices shows that the Aspirin subordinates display solid hindrance to the Bacillussubtilis and it show higher action than the first anti-inflamatory medicine. Lawal et al. (2006) discovered that the expansion of the cobalt and ferum metal with chlorine ligands shows the most noteworthy antibacterial action to hinders Bacillus subtilis.

Aspirin

• Aspirn (Acetyl Salicylic Acid) is a white crystalline weak acidic salicylicate that has analgesic and anti-inflammatory properties (Richard, C. B. 2012). It is also used to prevent cardiovasular disease and cancer (Cemel, A. and Ahmet, S. 2008).

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Aspirin: The Molecule

SYNTHESIS OF ASPIRIN

Synthesis

Purification

Characterization

Reactions

Synthesis procedure

• Mix salicylic acid derivatives (solid) with acetic anhydride (liquid) and a catalytic amount of H₂SO₄.

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• Heat for 10 min at 90⁰C.

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• Cool down to room temperature and add water (crystallization solvent).

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• Induce crystallization.

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• Filter the crystals.

Biological activity

• Analgesic (painkiller)
• Antipyretic (fever reducer)
• Anti-inflammatory (inhibition of the synthesis of prostaglandins)

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• Side effects: gastric irritation, bleeding

Apparition of new analgesics (Tylenol)

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Aspirin Synthesis

5-chlorosalicylic Acid+ Acetic Anhydride

Salicylic Acid+Acetic Anhydride

5-bromosalicylic Acid+ Acetic Anhydride

Mixtures + Heat

Reaction Mixtures (Cooled and crystallized) And tested with Ferric chloride (To remove unreacted salicylic acid

Salicylic acid derivatives + Acid anhydride

Mass Spectrophotometer Analysis

H-NMR Analysis

FTIR Analysis

Determination of the Melting Point of the Products