Difference between ¹H NMR signals of primary amide protons as a simple spectral index of the amide intramolecular hydrogen bond strength

Abstract

The effect of the intramolecular H‐bonding of the primary amide group on the spectral properties and reactivity of this group towards electrophiles has been studied in systematic rows of 1,2,5,6,7,8‐hexahydro‐7,7‐dimethyl‐2,5‐dioxo‐1‐R‐quinoline‐3‐carboxamides and 2‐aryliminocoumarin‐3‐carboxamides using 1H and 15N NMR spectroscopy and the kinetics of model reactions. The upfield signal of the amide proton that is not intramolecularly H‐bonded (Ha) depends on external factors such as solvent nature and concentration. At the same time, the downfield chemical shift of the Hb proton (bonded by the intramolecular hydrogen bond) depends mostly on the strength of the intramolecular H‐bond, which is affected by such internal factor as electron nature of substituent R. The substituent's influence on the Hb proton's chemical shift is more effective in deuterochloroform medium than in DMSO‐d6 where the intramolecular hydrogen bond is less stable. The value Δδ(H) = δ(Hb) − δ(Ha) is suggested as a simple comparative spectral index of the intramolecular hydrogen bond strength in these and similar compounds. By contrast, the effect of R on the 15N NMR chemical shift of the amide nitrogen has turned out to be too small to estimate changes of the electron density at the nitrogen. The effect of the intramolecular H‐bond on the reactivity of the amide group is twofold. When the cleavage of the H‐bond occurs on the rate limiting step it dramatically reduces the reaction rate. In the other case, the strengthening of the H‐bond favors the reaction rate because of the increase of the electron density at the amide nitrogen. Copyright © 2011 John Wiley & Sons, Ltd.

RuII(η6‐p‐cymene) Complexes of Bioactive 1,2‐Benzothiazines: Protein Binding vs. Antitumor Activity

“…This singlet splits into two separate broad singlets upon coordination to the Ru(cym) fragment and appeared at 6.06–6.38 (H b ) and 5.50–5.21 (H a ) ppm (in CDCl 3 ) with one integral for each signal (Figure 1). This may be due to the involvement of NH 2 protons in hydrogen bonding as has been reported for related compounds 17. The presence of hydrogen bonds was further corroborated in the molecular structures of 2a and 2b by single‐crystal X‐ray diffraction analysis (see below).…”

Internal plasticization of poly(vinyl) chloride using glutamic acid as a branched linker to incorporate four plasticizers per anchor point

“…Conjugation of the carbonyl amides to the triazole aromatic group results in downfield shifts of the amide protons. The differences between the 1 H chemical shifts of the two amides likely arises from intramolecular H‐bonding of the more downfield amide proton j at δ 11.3 ppm. The proton peaks of 6'a at δ 1.6, 1.4, and 0.9 [labeled g , h , and i in Fig.…”

Highly Polarized Coumarin Derivatives Revisited: Solvent‐Controlled Competition Between Proton‐Coupled Electron Transfer and Twisted Intramolecular Charge Transfer

“…It is well known that the chemical shift of a proton is proportional to the strength of a hydrogen bond it is involved in, and so NMR can be used as a technique for the characterization of hydrogen bonding in solution. To investigate the influence of solvents on hydrogen bonds in Amide‐PhF 5 and H‐Amide‐Ph , we performed additional NMR measurements in selected polar and nonpolar solvents (Figure SF5).…”