Very well reproducible but greener solvents need to be used

Details


Summary:

This paper reports the reactivity of the methylene group of 1-naphthyl-2-cyanoacetamide 1 which was tested towards different reagents. These new compounds have been reported to be characterized by elemental analysis, IR, 1HNMR, 13C NMR, and mass spectral analysis. Their in-vitro antibacterial activity against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria are also reported. Mild to moderate activity against the bacteria are reflected in the results. Since the compound 1 was used as the precursor for different types of products, the reaction sequences for each class of compounds were depicted by the authors in Schemes 1, 2, 3, 4, 5 and 6. The overall reaction schemes and the outcomes along with the recommendations are listed below:

Original Procedure:

  • Scheme 1 depicts the reaction: Equimolar amounts of 1 (0.21 g, 1 mmol) and the aldehydes 4-hydroxybenzaldehyde (0.122 g, 1 mmol) or piperonal (0.15 g, 1 mmol) in ethanol (15 mL) containing few drops of piperidine were heated under reflux for 30 min.
  • Equimolar amounts of 1 (0.21 g, 1 mmol) and the aldehydes 4-hydroxybenzaldehyde (0.122 g, 1 mmol) or piperonal (0.15 g, 1 mmol) in ethanol (15 mL) containing few drops of piperidine were heated under reflux for 30 min. Treatment of the latter compounds with malononitrile furnished the aminopyridone derivatives 6a, b. Formation of 6 may be proceeded via Michael type addition followed by auto-oxidation of the intermediates 4a, b. The structures of 6a, b were confirmed chemically by alternative synthesis, by reaction of 1 with the benzylidenemalononitriles 5 under a similar reaction conditions to give products identical in all respects (mp, mixed mp, and spectral analysis) with 6a, b (Scheme 1).
  • Schemes 2, 3, 4, 5 and 6 depict the syntheses of compounds 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23.

Modifications/ Comments:

  • The reported yields for 2a & 2b are 97% and 95% respectively. But, I found the actual yields to be around 82% in both cases. The yield of 6a and 6b obtained through the route using 5, was about 60% which is not very significant. The authors have mentioned another process of auto-oxidation in scheme 1, but did not mention the details. Nothing is mentioned about the characterization of compounds 3a, b and 4a, b.
  • The yields for some of the compounds were variable and often differing from the reported ones. 7 (72%), 8 (80%), 9 (30%), 10 (87%), 11 (67%) and 12 (69%). Other compounds could not be tested due to the huge number of compounds reported.
  • The formation of compound 9 took long time with very low yield than the reported one (Scheme 2).
  • The volatility of solvents increase upon heating, so the harmful impact on both human and environment will increase. The utilization of eco-friendly solvents will be useful.


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