Analysis of long‐range through‐space couplings via an intramolecular hydrogen bond

Abstract

In this work, 2-fluoro-benzamide (l), 2-fluoro-Nmethylbenzamide (2) and 2-fluoro-N,N-dimethylbenzamide (3) were chosen as model compounds in which to study long-range through-space couplings. In both 1 and 2 there should be strong intramolecular F-H bonds which would constitute eficient routes for transmitting nuclear spin information between the F atom and those of the amide moiety. The comparison of such couplings with those observed in the tertiary amide 3 can yield information about the transmission mechanisms that will help to define such couplings.* Author to whom correspondence should be addressed. It is also expected that different solvents would affect the coupling pathway without actually breaking the intramolecular hydrogen bond. There are strong intramolecular hydrogen bonds in o-salicylaldehyde derivatives' 2,1 and o-nitrophenol derivatives,'" for which it has been shown that a polar solvent increases the rapid exchange rate of the hydroxyl proton and destroys spin-spin c o u p h g associated with the OH, but the side-chain conformation remains adequate for intramolecular hydrogen bonding to take place. Traces of water, even in solvents of low polarity, can produce these effects.'" For this reason, side-chain parameters in 2 were also measured in four different solvents and the variations observed for both coupling constants and

Structure‐activity relationship study and NMR analysis of fluorobenzoyl pentapeptide GPR54 agonists

“…According to the results from NMR study in CDCl 3 , the molecules 13-24 may be classified into three groups: o-unsubstituted (13,15,16,20), o-monofluorinated (14, 17-19, 21, 22), and o,odifluorinated derivatives (23,24). An additional long-range spin-spin coupling between the aromatic fluorine and phenylalanine a-proton was observed only in o-monofluorinated derivatives, which supports the presence of interaction between the fluorine and the amide hydrogen (the longrange J coupling in 2-fluoro-N-methylbenzamide was reported 38 ). In addition, a significant downfield shift of NH signals was observed in o-monofluorinated derivatives compared to o-unsubstituted and o,o-difluorinated derivatives …”

“…In all spectra including o-monofluorinated derivatives, no long-range spin-spin couplings were observed, which indicated the absence of intramolecular hydrogen bonding between o-fluorine and amide hydrogen in DMSO. 38 Figure 2), which was in sharp contrast to the experiments in CDCl 3 . NMR analysis of whole structures of pentapeptide GPR54 agonists was also conducted in DMSO (Table IV).…”

A DFT and AIM analysis of the spin–spin couplings across the hydrogen bond in the 2‐fluorobenzamide and related compounds

“…These authors [6] established experimentally that the couplings were not through the bonds but through space involving an intramolecular N-H· · ·F hydrogen bond. The main argument was that 2-fluorobenzamide (1) and its N-methyl derivative (3) show spin-spin couplings between the aromatic fluorine and the nitrogen and carbon of the amide group, which are absent in the corresponding N,N-dimethylamide.…”

“…We should note that the important antibiotic PC190723 (2) [3 -5] shares part of the skeleton of 1. In 1993, Rae, Weigold, Contreras and Biekofsky [6] studied 1 (without being aware of the previous results [1,2] ) as well as its N-methyl 3 and N,N-dimethyl derivatives by 1 H, 13 C, 15 N and 19 F NMR spectroscopies (Table 2).…”

Hydrogen Bonding of Fluorinated Saccharides in Solution: F Acting as H‐Bond Acceptor in a Bifurcated H‐Bond of 4‐Fluorinated Levoglucosans

“…1) 15 N in peptides and nucleosides [9 -11]). 4 ) The h# J(Y,XH) (# ¼ digit) notation was introduced by Wüthrich and co-workers [12] to emphasise that one bond between the coupling partners Y and XH is a H-bond although couplings via Hbonds follow the same polarization mechanism as couplings via covalent bonds [9] [33], 2-fluoroanilines [22], and 2-fluorobenzamides [24], and a solvent-independent J(F,CH 3 ) value of 2.0 Hz was observed in 2-fluorotoluene [25]. The solvent dependence allows to discriminate between intramolecular H-bonds (solvent-dependent) and close contacts (solvent-independent), although, in the 2- To estimate the structural properties of 4-fluorinated levoglucosans that may qualify them as model compounds, as discussed in the Introduction, we compared the solid-statestructure of the myo-inositols 1 [17] and 6 [30] with that of levoglucosan (7) [34], and modeled the structure of the 4-fluorinated levoglucosan 9 and its defluoro analogue 21 (Fig.…”