Dr. Jugal Kishore Rai Deka, Postdoctoral Fellow, JNCASR, Bangalore | Department of Chemistry

Dr. Jugal Kishore Rai Deka, Postdoctoral Fellow, JNCASR, Bangalore

Abstract: N-acyl- and N,N'-diacylhydrazines have found applications in diverse fields such as pesticides, pharmaceuticals, polymer chemistry, dyestuffs, protein probes and chemical industries. They are also important building blocks for the chemical synthesis of a wide variety of biologically active heterocyclic scaffolds. Many natural products and aza-peptidomimetics contain N-acyl- and N,N'-diacylhydrazine motifs embedded in their structure. In addition, N-acyl- and N,N'-diacylhydrazines by themselves possess a wide range of biological activities. For example, RH-5849 (1,2-dibenzoyl-1-tert-butylhydrazine) and related N-alkyl-N,N'-diacylhydrazines are potent pesticides that were marketed in the 1980s. Despite their huge significance in chemistry and biology, the conformational properties of these molecules have remained poorly understood. In N-acylhydrazines (R1-CO-R2N–NR3R4), one of the nitrogen atoms is amidic in character whereas the other nitrogen atom contains a free electron pair. On the other hand, in N,N-diacylhydrazines (R1–CO–NR3–NR4–CO–R2) both the nitrogen atoms are of amide character. The three-dimensional structures of these molecules are often described by the repulsion between their nitrogen lone pairs. In this thesis, we have carried out systematic investigations of the conformational properties of various N-acyl- and N,N'-diacylhydrazines. We first studied the conformational properties of ~60 N,N'-diacylhydrazines using gas phase theoretical calculations, solution phase 1D and 2D NMR spectroscopy and solid-state X-ray crystallography. We observed that when the substituents on nitrogen atoms are hydrogens, the N,N'-diacylhydrazines predominantly adopted trans-trans (t-t) (> 90%) amide bond geometries (H-N-C=O ~180°) whereas both N-alkylated and N,N'-dialkylated N,N'-diacylhydrazines preferred trans-cis (t-c) amide bond geometries. We discovered that the amidic nitrogen lone pairs can participate in unusual nN → σ*/π*Ar interactions with σ* or π*Ar orbital on the acyl substituents and modulate the conformational preference of N,N'-diacylhydrazines. In N-arylhydrazides, where one of the nitrogen lone pairs is free, the nN → π*Ar interactions were much stronger and they play vital roles in stabilizing the E-ac conformer of these molecules. We also observed that when a leaving group such as F was present in the aryl ring at the ortho-position of the CO group, nN → π*Ar interactions facilitated an intramolecular SNAr auto-cyclization reaction to produce indazolone, a heterocycle with a wide range of biological activities. Our results provide a structural basis for the accurate prediction of the most stable conformation as well as the relative population of various amide bond rotamers of N-acyl- and N,N'-diacylhydrazines in solution. Overall, our study revealed the importance of various previously unappreciated weak noncovalent interactions in the stabilization of N-acyl- and N,N'-diacylhydrazines, which should also be important in other N─N bond containing systems that contain N-acyl- and N,N'-diacylhydrazine motifs embedded in their structure.

Email: jd918@snu.edu.in

Profile Summary: 

Ph.D. dissertation, Shiv Nadar University 2021 "Conformational properties of N-acyl- and N,N'-diacylhydrazines: Discovery of some unusual noncovalent interactions involving their nitrogen atoms"

List of publications:

included in the thesis:

1.  Deka, J. K. R.; Sahariah, B.; Baruah, K.; Bar, A. K.; Sarma, B. K. Conformational control of N-methyl-N,N'-diacylhydrazines by noncovalent carbon bonding in solution. Chem. Commun. 2020, 56 (36), 4874-4877.

Note: This work has been published as a front cover: Chem Commun202056, 4861-4960. ISSN 1359-7345.

2.  Deka, J. K. R.; Sahariah, B.; Sakpal, S. S.; Bar, A. K.; Bagchi, S.; Sarma, B. K. Evidence of an nN(amide)→π*Ar interaction in N-Alkyl-N,N'-diacylhydrazines. Org. Lett. 2021, 23 (18), 7003-7007.

Note: This work has been published as a front cover: Org. Lett202123 (18), 7003-7312.

3.  Deka, J. K. R.; Kalita, D.; Sahariah, B.; Sarma, B. K. nN→π*Ar interactions stabilize the E-ac isomers of arylhydrazides and facilitate their SNAr autocyclizations. Chem. Commun. 2021, 57 (85), 11236-11239.

4.  Deka, J. K. R.; Sahariah, B.; Baruah, K.; Kalita, D.; Sarma, B. K. Conformational properties of N, N¢-diacylhydrazines: Understanding the steric and stereoelectronic effects to develop guidelines for their a priori structure prediction. (Manuscript under preparation).

Not included in the thesis:

1.  Baruah, K.; Sahariah, B.; Sakpal, S. S.; Deka, J. K. R.; Bar, A. K.; Bagchi, S.; Sarma, B. K. Stabilization of azapeptides by Namide···H-Namide Hydrogen Bonds. Org. Lett. 2021, 23 (13), 4949-4954.

2.  Rahim, A.; Baruah, K.; Sahariah, B.; Deka, J. K. R.; Sarma, B. K. Solid-phase synthesis of hybrid 2,5-diketopiperazines using acylhydrazide, carbazate, semicarbazide, amino acid, and Primary Amine submonomers. J. Org. Chem. 2020, 85 (5), 2927-2937.

Research Advisor: Dr. Bani Kant Sarma, Former Faculty

Research Type: