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
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.