Delocalization Of Nitrogen Lone Pair Research Articles

Synthesis, spectral characterization and conformational assignment of N-formyl-2,7-diaryl-1,4-diazepan-5-ones as potent antibacterial agents and type I DHQase inhibitors

• Four N -formyldiazepan-5-ones are synthesized and characterized by IR, mass and NMR spectra. • The conformational assignment is made by NMR spectral studies. • All the formamides prefer to adopt flattened boat conformations. • Antibacterial efficacy for 9-12 have been evaluated by resazurin reduction assay. • Molecular docking is performed for 9-12 with type 1 3-DHQase protein target. Four new N -formyl-1,4-diazepan-5-ones 9-12 have been synthesized and their spectral characterization is made using IR, mass and NMR spectra. In NMR spectra, the compounds 9-12 show doubling of NMR spectral signals due to the delocalization of nitrogen lone pair into the carbonyl П cloud and thereby creating a partial double character at N C(= O ) bond which results in an equilibrium between syn and anti rotamers. The preferred conformations of N -formyl-1,4-diazepan-5-ones 9-12 are arrived from the NMR spectral data, dihedral angles (°) and destabilizing strain factors. The syn and anti rotamers of these compounds prefer to adopt equilibrium between flattened boat conformations with quasi-axial orientations of aryl groups at C-2 and C-7. Furthermore, all the compounds are active against all the tested bacterial strains. The compounds 9 & 10 against E. coli strain, compound 11 against B. cereus strain and compounds 11 & 12 against S. typhi strain show equal potency as that of standard drug Streptomycin. Hence, the formamides 9-12 are believed to be good antibacterial agents. The synthesised molecules are subjected to molecular docking studies with 3-dehydroquinate dehydratase (DHQase) protein. The molecular modelling studies exhibit high inhibition and binding energy are conforming to antibacterial activity. The compounds 9-12 exhibit better docking score and glide energy than that of DHQase co-crystallized ligand.

Synthesis, spectroscopic and conformational analysis of 1,4-dihydroisonicotinic acid derivatives

Structural and conformational properties of 1,4-dihydroisonicotinic acid derivatives, characterized by ester, ketone or cyano functions at positions 3 and 5 in solid and liquid states have been investigated by X-ray analysis and nuclear magnetic resonance and supported by quantum chemical calculations. The dihydropyridine ring in each of the compounds exists in flattened boat-type conformation. The observed ring distortions around the C(4) and N(1) atoms are interrelated. The substituent at N(1) has great influence on nitrogen atom pyramidality. The 1H, 13C and 15N NMR chemical shifts and coupling constants are discussed in terms of their relationship to structural features such as character and position of the substituent in heterocycle, N-alkyl substitution and nitrogen lone pair delocalization within the conjugated system.

Spectral analysis, structural elucidation and evaluation of chemical reactivity of synthesized ethyl-4-[(2-cyano-acetyl)-hydrazonomethyl]-3,5-dimethyl-1H-pyrrole-2-carboxylate through experimental studies and quantum chemical calculations

This paper describes the synthesis, spectral analysis, structural elucidation and chemical reactivity of pyrrole hydrazide–hydrazone: ethyl-4-[(2-cyano-acetyl)-hydrazonomethyl]-3,5-dimethyl-1H-pyrrole-2-carboxylate (ECAHDPC). The 1H, 13C NMR isotropic chemical shifts and electronic absorption spectra have been calculated by GIAO and TD-DFT methods, respectively, and corroborate well with experimental data. The NH proton of the hydrazide–hydrazones (CNNHCO) frame appears as singlet at δ=11.69ppm due to delocalization of nitrogen lone pair with carbonyl group and its proton involvement in intramolecular H-bonding. The calculated wavenumbers of dimer are in good agreement with the experimental results and confirm that the stable conformer forms dimer by hydrogen bonding interactions between pyrrolic NH and carbonyl CO group of ester giving red shift and resonance assisted hydrogen bonding. The binding energy of intermolecular interaction is found to be 10.19kcal/mol after basis set superposition error correction. QTAIM calculations confirm the existence of intermolecular conventional hydrogen bond (NH⋯O), intra and intermolecular non-conventional hydrogen bond (CH⋯O) and intramolecular interaction (C⋯N). The NBO analysis has been performed to evaluate charge transfer and delocalization of electron density. The static first hyperpolarizability (β0) of monomer has been found to be 6.59×10–30esu. The maximum value of reactivity descriptors (fk+, sk+, ωk+) at C(9) indicate that this site is more susceptible to nucleophilic attack, favoring for the formation of heterocyclic compounds.

New diketopyrrolopyrrole (DPP) derivative as fluorescent probe for Zn2+

New turn-on fluorescent probe DPPL2, was rationally designed and synthesized based on the skeleton of diketopyrrolopyrrole (DPP), which presented sensitivity, selectivity for Zn2+ over other metal ions except some disturbance with Cd2+. Particularly, results demonstrated fluorescence enhancement and blue shift of DPPL2 upon Zn2+ binding. This phenomenon was a typical photoinduced electron transfer (PET) and intramolecular charge transfer (ICT) process which was attributed to diminishing the electron of the nitrogen lone pair delocalization on the DPP core upon Zn2+ binding. For comparison, DPPL3 (acylation of nitrogen atom of DPPL2) was synthesized and no fluorescence enhancement was observed, which further indicated that lone pair electrons of nitrogen atoms attached to DPP core were ascribed to PET process. 1H NMR titrations and DFT calculations also proved that PET and ICT process of system.

15N NMR of 1,4‐dihydropyridine derivatives

In this article, we describe the characteristic (15)N and (1)HN NMR chemical shifts and (1)J((15)N-(1)H) coupling constants of various symmetrically and unsymmetrically substituted 1,4-dihydropyridine derivatives. The NMR chemical shifts and coupling constants are discussed in terms of their relationship to structural features such as character and position of the substituent in heterocycle, N-alkyl substitution, nitrogen lone pair delocalization within the conjugated system, and steric effects.

Sensitivity of the H/D isotope shifts of the 13C nuclear shielding to the nitrogen lone pair delocalization in anilines and acetanilides

AbstractTwo‐ and three‐bond deuterium isotope shifts (2Δ and 3Δ) of the 13C nuclear shielding were measured for a series of para‐substituted anilines and acetanilides, in which the amide NH or the amine NH2 hydrogens were partially exchanged with deuterium. The results show that when strong electron‐donating groups are present at the para position in acetanilides, the 2Δ(C‐1) isotope shifts are smaller than the 3Δ(C‐2,6) isotope shifts. Empirical correlations that relate 2Δ isotope shifts with 1H(NH), 13C(C‐ipso), 15N(NH2 or NH), 17O(CO) NMR chemical shifts and with 3Δ isotope shifts are presented. The results are interpreted in each series as depending on the characteristic nitrogen lone pair delocalization.

Crystal structure of 2,2,4,4-tetrachloro-6,6-bis(trimethylsilylamino)cyclo-triphosphazene, N3P3Cl4(NHSiMe3)2

The X-ray crystal structure of N3P3Cl4(NHSiMe3)2 has been determined. Crystals are monoclinic, space group C2/c, with a= 13.749(6), b= 7.343(3), c= 20.124(3)A, β= 95.24(3)°, and Z= 4; R= 0.049 for 961 unique observed reflections. The phosphazene ring lies on a crystallographic two-fold axis and is planar within 0.031(2)A. The exo P–N bond distance is 1.609(5) and the Si–N bond distance is 1.757(5)A which suggests preferential nitrogen lone pair delocalization to the phosphorus atom. The P–N distances in the ring alternate (from the P with the exo N atoms) from 1.617(5) to 1.551(5) to 1.591(4)A. The structural and 31P n.m.r. parameters of N3P3Cl4(NHSiMe3)2 are compared to those of the analogous t-butylamino derivative.

Electronic delocalization in NC and NN bonds

AbstractFor a series of compounds with NC or NN bonds, the CNDO/S parameterized calculations for Qπ, the electronic charge density on the nitrogen atom, and π bond orders Pπ provide evidence for the simultaneous dependence of the 15N chemical shift on both of these parameters. The multilinear regressions obtained produce high values for the regression coefficients. The results throw some light on the nitrogen lone pair delocalization mechanism.

13C nuclear magnetic resonance spectroscopy of nitrogen heterocycles. Part 4. intra-extra Configuration of the N-acetyl group in phenothiazine and related systems with a ‘butterfly’ shape

Nitrogen lone-pair delocalization into aromatic rings has been studied for phenothiazine, N-acetylphenothiazine, and related tricyclic systems with a ‘butterfly’ conformation, by using 13C n.m.r. spectroscopy. Pyridazo[4,5-d][1,4]benzothiazines, phenoxazines, acridane, and simple model compounds such as diphenylamine, 2-methylthioaniline, and their corresponding N-acetyl derivatives were examined. The preferred configuration of the N-acetyl group has been determined for CDCl3 and Me2SO solutions. Nitrogen lone-pair delocalization of the N-acetyl group into the aromatic system is strongly hindered for all tricyclic compounds, and greatly reduced for N-acetyldiphenylamine and also for 2-methylthioacetanilide in Me2SO. For this last compound, the decrease of conjugation is due to a solvent-induced change of conformation; for tricyclic systems it is a consequence of the preferred extra-configuration of the N-acetyl group.

Electronic and steric effects in arylphosphoramidates and phosphorimidates as monitored by carbon‐13 nuclear magnetic resonance

Abstract13C NMR chemical shifts and 13C31P couplings are reported for ten arylphosphoramidates and five arylphoshorimidates. The para‐carbon chemical shifts in the phosphoramidates are interpreted in terms of substantial nitrogen lone pair delocalization into the aromatic ring, a phenomenon which is subject to steric inhibition of resonance. By contrast, in the phosphorimidates the electron release into the phenyl ring is not attenuated by steric congestion. Conformational changes about the arylN bond in all compounds have been monitored by vicinal 31PNC13C couplings.

Applications of 15N NMR spectroscopy to the study of unsymmetrically N‐substituted amides and model peptide compounds

Abstract13C and 15N spectra of unsymmetrically N‐substituted formamides and alkyl‐, substituted alkyl‐, and arylcarboxamides, which can be considered as model peptide compounds, were determined and discussed in terms of nitrogen lone pair delocalization. Differential solvent shifts and through‐space steric effects are considered as a tentative explanation of the difference in screening between geometrical diastereoisomers. Z‐E assignment and the thermodynamic stability of diastereoisomers can also be predicted in some circumstances from a consideration of the 15N chemical shifts. Data concerning small peptides are discussed in the light of the results obtained using the model compounds.

15N n.m.r.: Substituent effects on nitrogen chemical shifts in anilinium ions

Abstract15N chemical shifts were measured in a series of anilinium fluorosulfonate salts and compared with chemical shift data from a comparable series of 15N‐enriched aniline derivatives. A smaller overall range of nitrogen chemical shifts was observed for the protonated aniline series compared with that for the unprotonated anilines and is attributed to the elimination of nitrogen lone pair delocalization in the former series. Further‐more, it was found that the range of nitrogen chemical shifts in the protonated anilines is determined primarily by substituent electronic effects from the ortho ring position with almost negligible contributions from the para position.