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. 2021 Aug 13;26(16):4908.
doi: 10.3390/molecules26164908.

Synthesis of Novel N-Acylhydrazones and Their C-N/N-N Bond Conformational Characterization by NMR Spectroscopy

Rubina Munir  1   2 , Noman Javid  3 , Muhammad Zia-Ur-Rehman  4 , Muhammad Zaheer  4 , Rahila Huma  2 , Ayesha Roohi  2 , Muhammad Makshoof Athar  1
Affiliations

Synthesis of Novel N-Acylhydrazones and Their C-N/N-N Bond Conformational Characterization by NMR Spectroscopy

Rubina Munir et al. Molecules. .

Abstract

In this article, a synthesis of N'-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides and their structural interpretation by NMR experiments is described in an attempt to explain the duplication of some peaks in their 1H- and 13C-NMR spectra. Twenty new 6-methyl-1H-pyrazolo[3,4-b]quinoline substituted N-acylhydrazones 6(a-t) were synthesized from 2-chloro-6-methylquinoline-3-carbaldehyde (1) in four steps. 2-Chloro-6-methylquinoline-3-carbaldehyde (1) afforded 6-methyl-1H-pyrazolo[3,4-b]quinoline (2), which upon N-alkylation yielded 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetate (3). The hydrazinolysis of 3 followed by the condensation of resulting 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazide (4) with aromatic aldehydes gave N-acylhydrazones 6(a-t). Structures of the synthesized compounds were established by readily available techniques such as FT-IR, NMR and mass spectral studies. The stereochemical behavior of 6(a-t) was studied in dimethyl sulfoxide-d6 solvent by means of 1H NMR and 13C NMR techniques at room temperature. NMR spectra revealed the presence of N'-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides as a mixture of two conformers, i.e., E(C=N)(N-N) synperiplanar and E(C=N)(N-N)antiperiplanar at room temperature in DMSO-d6. The ratio of both conformers was also calculated and E(C=N) (N-N) syn-periplanar conformer was established to be in higher percentage in equilibrium with the E(C=N) (N-N)anti-periplanar form.

Keywords: NMR; acylhydrazone; conformer; pyrazolo[3,4-b]quinoline; quinoline; rotamer; stereoisomer.

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Conflict of interest statement

The authors declare that they have no significant conflict of interest.

Figures

Figure 1
Figure 1
Stereoisomers of N-Acylhydrazones.
Scheme 1
Scheme 1
Synthesis of 6-methyl-1H-pyrazolo[3,4-b]quinoline substituted N-acylhydrazones 6(a–t).
Figure 2
Figure 2
(a) 1H NMR and (b) 13C NMR spectra of N-Acylhydrazone 6k.
Figure 2
Figure 2
(a) 1H NMR and (b) 13C NMR spectra of N-Acylhydrazone 6k.
Figure 3
Figure 3
Rotational isomers arising due to C-N Bond C(O)-NH rotation.
Figure 4
Figure 4
All the possible stereoisomers of N-Acylhydrazones 6(a–t).
Figure 5
Figure 5
Possible interactions of E-Isomer in solution.
Figure 6
Figure 6
Possible intramolecular interactions in E(C=N) (N-N)—Antiperiplanar form of 6q.
See this image and copyright information in PMC

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