Eco-Friendly and Highly Efficient Synthesis, Including Multigram Synthesis, of Aldehyde Isonicotinoyl Hydrazones Using Sonochemistry

Author(s): Ligia S. da Silveira Pinto, Marcus V.N. de Souza, Emerson T. da Silva, Carlos R. Kaiser, Solange M.S.V. Wardell, James L. Wardell.

Journal Name: Letters in Organic Chemistry

Volume 13 , Issue 8 , 2016

Submit Manuscript
Submit Proposal

Graphical Abstract:


Abstract:

Background: The isoniazid has been a key compound in first-line tuberculosis (TB) treatment, usually in combination with other drugs. Following on from the use of isoniazid itself, various derivatives of isoniazid have also been investigated as anti-TB agents and other diseases. This work aims to synthesize, multigram scale, salicylaldehyde isonicotinoyl hydrazone from isoniazid and salicylaldehyde, using ultrasound. Additionally, we have been interested in establishing a general, smaller-scale, ultrasonic driven synthesis of arylaldehyde isoniazid N-acylhydrazones, particularly for use in our biological studies.

Methods: A Multiwave Eco-Sonics QR750 ultrasonic generator (20 KHz, 750 W) equipped with a converter/ transducer, and titanium oscillator (horn, diameter = 4 mm) was used for the ultrasonic irradiantion. Compounds were characterized by melting points, infrared spectra, mass spectra (CG/MS), electron microscopy, X-ray powder diffraction, solid-state 13C and solution NMR spectra.

Results: This work describes a green chemistry protocol, multigram scale (ca 4 mole) and highly efficient synthesis utilizing ultrasonic irradiation of salicylaldehyde isonicotinoyl hydrazone, a widely used compound in biological studies. With a short reaction time of 30 min, and a facile work up, involving washing with water, the important bioactive product was obtained in a high yield, 98.7%, and in a high purity 99.43%. Also prepared using ultrasonic irradiation with short reaction times, in high yields and high purities, but on smaller scales, were a series arylaldehyde isoniazid N-acylhydrazones, all of which exhibit promising activity against cancer and tuberculosis. Comparisons with the classical procedures indicate advantages in the ultrasonic irradiated methodology.

Conclusion: We report the high yielding ultrasonic synthesis of pure salicylaldehyde isonicotinoyl hydrazone on a 4 mole scale. In addition, a series of ten isoniazid N-acylhydrazone derivatives has been obtained using ultrasonic irradiation. The ultrasonic procedures are simple, safe, with short reaction times, and produce high yields.

Keywords: Green chemistry, isoniazid, N-acylhydrazone, SIH, bioactive, sonochemistry.

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 13
ISSUE: 8
Year: 2016
Page: [585 - 590]
Pages: 6
DOI: 10.2174/1570178613666160824123827
Price: $58

Article Metrics

PDF: 26
HTML: 2
EPUB: 1
PRC: 1