Multinuclear magnetic resonance analysis of 2-(trifluoromethyl)-2-oxazoline

(1)H, (19)F, (13)C, (15)N, and (17)O NMR chemical shifts and (1)H-(1)H, (1)H-(19)F, (1)H-(13)C, (19)F-(13)C, and (19)F-(15)N coupling constants are reported for 2-(trifluoromethyl)-2-oxazoline.     

19F and 1H NMR spectra of halocarbons

19F NMR chemical shifts and coupling constants are reported for 215 compounds. For 77 of these compounds, 1H NMR spectral data are also given. Long-range couplings, including 8J(F,F) and 5J(F,H), are reported. The complexity of halocarbon spectra owing to the presence of rotational isomers, asymmetric centers, long-range couplings, and chlorine isotope effects are illustrated, and the methods used for analyzing such complex spectra are briefly discussed.     

13C NMR spectra of some 1-, 3- and 4-monosubstituted and disubstituted isoquinolines

Chemical shifts and substituent chemical shift (SCS) effects are reported for 21 monosubstituted iso-quinolines, carrying a halogeno, amino, piperidino or ethoxy group in position 1, 3 or 4. In some cases, assignments of ¹³C resonances were based on the spectra of the corresponding 5-deutero derivatives. For the fluoroisoquinolines some ¹³CF coupling constants are given. The ¹³C NMR spectra of 15 disubstituted isoquinolines were measured; with a few exceptions, mainly the 3,4- and 1,4-disubstituted isoquinolines, the chemical shifts agreed well with those calculated by addition of the SCS effects.     

Unambiguous assignment of trifluoromethylpyrazole regioisomers by 19F-15N correlation spectroscopy

Analysis of the 19F chemical shifts of trifluoromethylpyrazole regioisomers has shown that while chemical shift is in general a reliable predictor of regiochemistry in this series, there is a narrow chemical shift range in which the two isomers overlap and the regiochemistry cannot be assigned with certainty. We have examined the usage of 19F--15N correlation spectroscopy as a method to provide a second unambiguous confirmation of regiochemistry of 3- and 5-trifluoromethylpyrazole regioisomers. In the case of 3-trifluoromethyl analogs, one expects a three-bond coupling to the pyridine type nitrogen (N-2). In the case of the 5-trifluoromethyl pyrazole the situation is exactly reversed, with the fluorines of the trifluoromethyl moiety being 3-bonds from the pyrrole type nitrogen (N-1). We have observed that 3-trifluromethyl analogs follow the expected pattern of readily observable 3-bond coupling. However, 19F--15N couplings in 5-trifluromethyl analogs do not follow the normal pattern of 3-bond coupling. Using this information we have been able to develop unambiguous methods to distinguish the isomers.     

Mono‐ and difluorinated 1,1,2,2,9,9,10,10‐octafluoro[2.2]paracyclophanes (AF4s)—A 1H and 19F NMR study

Complete assignment of the ¹H and ¹⁹F chemical shifts in 4‐fluoro‐AF4 (1) were based on the nOes seen in its ¹⁹F‐¹H HOESY spectrum. This allowed for identification of features which can further be applied to the assignment of the regiochemistry of substituted perfluoroparacyclophanes (PCPs) and AF4s: (i) an aromatic fluorine couples with the two fluorines in the closest bridge that are syn to it, with constants of ca. 20 Hz; (ii) an aromatic fluorine couples with the bridge fluorine five bonds away that is anti to it in the same paraphenylene moiety, with a constant of ca. 3.5 Hz; (iii) the geminal coupling of the bridge fluorines is 246 Hz if they have an ortho fluorine and 238 Hz if they do not; (iv) a bridge fluorine couples with those aromatic protons in the same paraphenylene moiety that are four or five bonds away and anti. These features have been used to assign the regiochemistry of the pseudo‐ortho, pseudo‐meta and pseudo‐para‐difluoro AF4s 2–4. It has also been demonstrated that SCS for the bridge fluorines can be used as well for this assignment. Copyright © 2009 John Wiley & Sons, Ltd.     

Spin-spin coupling and substituent and halogen isotope shift effects in the fluorine NMR spectra of fluorinated cyclopropanes and cyclopropyl ethers

The (19)F NMR spectra of a series of fluorinated cyclopropanes, most of which contain chlorine or bromine on the ring, have been observed and analyzed. A scheme has been developed to assign the resonances and the molecular stereochemistry, based on substituent effects, comparison of related molecules, and isotope shifts induced by the halogens. Replacement of fluorine by chlorine shifts cis fluorine resonances to lower field, and bromine has an even greater downfield influence. However, the shift effect of bromine compared to chlorine on gem or trans fluorines is variable. The magnitude of the isotope shifts is found to be regularly related to the geometrical relationship of the halogen to the observed fluorine and thus makes a significant contribution to the fluorine assignments. The three-bond spin-spin coupling constants between fluorine atoms in cyclopropanes display unusual behavior and are not helpful for assignment of the fluorine resonances. The signs of the coupling constants have been investigated by spin-tickling experiments, and the previously developed relation of the coupling constant sign to its temperature dependence has been found to be violated for some molecules.     

Additivity scheme in nmr chemical shifts of disubstituted pyridines

An additivity relationship for chemical shifts similar to that found in the literature for coupling constants has been tested in eleven disubstituted pyridines. The chemical shifts of these disubstituted pyridines were measured in different solvents at different concentrations and extrapolated to infinite dilution.In order to compute the “effects” of the different substituents, the chemical shifts of the corresponding monosubstituted pyridines and of pyridine were measured in the same solvents at different concentrations. These chemical shifts were extrapolated to infinite dilution.In most cases it was found that the extrapolated chemical shifts for disubstituted pyridines are in good agreement with those calculated using the additivity relationship. Only in a few cases was it found that the additivity scheme does not hold.     

A 1H NMR and theoretical investigation of the conformations of some monosubstituted cyclobutanes

The complete analysis of the complex (1)H NMR spectra of some monosubstituted cyclobutanes was achieved to give all the (1)H chemical shifts and (n)J(HH) (n = 2, 3 and 4) coupling constants in these molecules. The substituent chemical shifts of the substituents in the cyclobutane ring differ significantly from those in acyclic systems. For example, the OH and the NH(2) groups in cyclobutanol and cyclobutylamine produce a large shielding of the hydrogens of the opposite CH(2) group of the ring compared with little effect on the comparable methylene protons of butane. These effects and the other (1)H shifts in the cyclobutanes were modelled successfully in the CHARGE program. The RMS error (calculated vs observed shifts) for the 34 (1)H shifts recorded was 0.053 ppm. The conformational equilibrium in these compounds between the axial and the equatorial conformers was obtained by comparing the observed and the calculated (4)J(HH) couplings. These couplings in cyclobutanes, in contrast to the corresponding (3)J(HH) couplings, show a pronounced orientation dependence; (4)J(eq-eq) is ca 5 Hz and (4)J(ax-ax) ca 0 Hz. The couplings in the individual conformers were calculated at the B3LYP/EPR-III level. The conformer energy differences ΔG(ax-eq) vary from 1.1 kcal mol(-1) for OH to 0.2 kcal mol(-1) for the CH(2)OH substituent. The values of the conformer energy differences are compared with the previous IR data and the corresponding theoretical values from molecular mechanics (MM) and DFT theory. Generally, good agreement is observed although both the MM and the DFT calculations deviate significantly from the observed values for some substituents.     

The proton magnetic resonance spectra of some disubstituted acetophenones

An accurate measurement of the chemical shifts and the coupling constants of some disubstituted acetophenones has been made. The acetophenones studied contained nitro, bromo or amino groups substituted in either the 3,4 or 2,5 positions. For compounds with no substituent adjacent to the acetyl group, the chemical shifts and the coupling constants estimated by the simple additivity of the substituent increments were found to be in reasonable agreement with the experimental values. The two nitro, bromo derivatives substituted in positions 2 and 5 probably prefer the conformer in which the proton H-6 is adjacent to the acetyl methyl group whilst the 3,4-disubstituted bromo, nitro and bromo, amino derivatives prefer the conformer in which the H-6 proton is adjacent to the carbonyl group.     

Full multinuclear resonance analysis of 4-amino-1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane

The complete assignment of 19F, 1H and 13C NMR spectra for a monosubstituted octafluoro[2.2]paracyclophane derivative is described for the first time. The unambiguous assignments were achieved through the combination of 19F--1H HOESY, 1H COSY and 19F COSY techniques and then further confirmed employing a complementary approach using a Karplus-dependent 3JCF interaction. Interesting aspects of the coupling patterns for various JHH, JHF, JCF and JFF interactions are also discussed.     

Computation and analysis of 19F substituent chemical shifts of some bridgehead‐substituted polycyclic alkyl fluorides

The ¹⁹F NMR shieldings for several remotely substituted rigid polycyclic alkyl fluorides with common sets of substituents covering a wide range of electronic effects were calculated using the DFT‐GIAO theoretical model. The level of theory, B3LYP/6–311+G(2d,p), was chosen based on trial calculations which gave good agreement with experimental values where known. The optimized geometries were used to obtain various molecular parameters (fluorine natural charges, electron occupancies on fluorine of lone pairs and of the C? F bond, and hybridization states) by means of natural bond orbital (NBO) analysis which could help in understanding electronic transmission mechanisms underlying ¹⁹F substituent chemical shifts (SCS) in these systems. Linear regression analysis was employed to explore the relationship between the calculated ¹⁹F SCS and polar substituent constants and also the NBO derived molecular parameters. The ¹⁹F SCS are best described by an electronegativity parameter. The most pertinent molecular parameters appear to be the occupation number of the NBO p‐type fluorine lone pair and the occupation number of the C? F antibonding orbital. This trend suggests that in these types of rigid saturated systems hyperconjugative interactions play a key role in determining the ¹⁹F SCS. Electrostatic field effects appear to be relatively unimportant. Copyright © 2003 John Wiley & Sons, Ltd.     

Characterization by NMR of reactants and products of hydrofluoroether isomers,CF3(CF2)3OCH3 and (CF3)2C(F)CF2OCH3, reacting with isopropyl alcohol

The 3M Company product Novec? 71IPA DL, a mixture of methoxyperfluorobutane, methoxyperfluoroisobutane and 4.5 wt.% isopropyl alcohol, has been found to be very stable at ambient temperature, producing fluoride at the rate of ~1 ppm/year. Our earlier kinetic and theoretical studies have identified the reaction mechanism. This paper identifies the ¹H and ¹⁹F NMR chemical shifts, multiplicities, and coupling constants of reactants and the major products that result from aging the mixture in sealed Pyrex NMR tubes for periods up to 1.8 years at temperatures from 26 °C to 102 °C. Chemical shifts and coupling constants of fluorine and hydrogen atoms on the hydrofluoroethers and isopropyl alcohol are traced through the reactions to their values in the products – esters, isopropylmethyl ether, and HF. These spectral positions, multiplicities, and coupling constants are presented in table format and as figures to clarify the transformations observed as the samples age. Copyright © 2013 John Wiley & Sons, Ltd.     

Through‐space 19F–15N couplings for the assignment of stereochemistry in flubenzimine

Through‐space ¹⁹F–¹⁵N couplings revealed the configuration of flubenzimine, with the CF₃ group on N4 pointing towards the lone pair of N5. The ¹⁹F–¹⁵N coupling constants were measured at natural abundance using a spin‐state selective indirect‐detection pulse sequence. As ¹⁵N‐labelled proteins are routinely synthesized for NMR studies, through‐space ¹⁹F–¹⁵N couplings have the potential to probe the stereochemistry of these proteins by ¹⁹F labelling of some amino acids or can reveal the site of docking of fluorine‐containing drugs. Copyright © 2016 John Wiley & Sons, Ltd.     

13C?19F spin–spin coupling in some monofluoro-substituted polycyclic aromatic hydrocarbons

The determination and complete assignment of the ¹³C? ¹⁹F coupling constants and ¹³C chemical shifts for 15 monofluoro derivatives of nine polycyclic aromatic hydrocarbons are reported. Fluorine substitutent effects on the ¹³C chemical shifts are given and their regular behaviour, making comparisons between different compounds possible, is discussed. The numerical values of the ¹³C? ¹⁹F long range coupling constants are found, with a few exceptions, to decrease in an alternating manner along the periphery of the molecules. In several cases the signs of the coupling constants have been determined. It appears that the signs alternate, but additional evidence is required. The magnitudes of different types of coupling constants are discussed in terms of steric and electronic effects. CNDO/2 and INDO calculations of the ¹³C? ¹⁹F coupling constants in the fluoronaphthalenes have been performed using the ‘sum-over-states’ method with the aim of examining the orbital and spin–dipole contributions to the various couplings.     

Carbon-13 nuclear magnetic resonance spectroscopy IX—monosubstituted ethylenes

Carbon-13 chemical shifts of sixteen monosubstituted ethylenes were obtained. In order to explain the chemical shifts, σ and π electron densities of these compounds are calculated by the σ-included ω-HMO method.

1 See Ref. 8.

A linear relationship exists between carbon-13 chemical shifts and the calculated electron densities, and also between substituent constants and electron densities. A slope of unity is obtained between the chemical shifts of α carbons of monosubstituted ethylenes and those of carbons adjacent to the substituents in monosubstituted benzenes. On the other hand, a plot of chemical shifts of C_ortho of benzene derivatives against that of the β carbon in ethylene derivatives gives a slope of 3. These slopes can be explained by the calculated electron densities. A slope of 4/3 is obtained between the direct coupling constant ¹J(C? H) of the α carbon in monosubstituted ethylenes and that in the corresponding substituted methanes.     

Self-consistent Perturbation Theory of 13C magnetic resonance parameters in pyridines

The ¹³C chemical shifts for pyridine and 22 of its monosubstituted derivatives, the ¹³C? ¹⁹F couplings for fluoropyridines and the ¹³C? ¹⁵N couplings for pyridine, the pyridinium cation and pyridine-N-oxide have been calculated using the SCF-INDO Finite Perturbation Theory. Experimental ¹³C chemical shifts show only modest correlation with calculated shieldings; trends and magnitudes are, however, reasonably reproduced in some cases. Theory yields a correct account of the magnitudes, signs and trends for the various couplings except for ²J(CF). Addition of an empirical correction of + 33.5 Hz to the Fermi contact term leads also to excellent reproduction of this coupling.     

1H and 13C NMR spectral assignment of androstane derivatives

(1)H and (13)C NMR spectroscopic data for 5alpha-androstanes and halo-5alpha-androstanes with different substituents at positions C-3, C-9, C-11 and C-17 were examined and assigned by a combination of 1D and 2D NMR experiments. The substituent effects on the (13)C chemical shifts were compared with those of epi-androsterone, used as a reference compound. The coupling constants (n)J((19)F,(13)C) were measured for compounds 6, 8, 11 and 14.     

A correlation of substituent effects with proton chemical shifts in aromatic tetrazolic acids

The effect of substituents on the proton chemical shifts and spin–spin coupling constants in ortho-, meta- and para-substituted 5-phenyltetrazoles (tetrazolic acids) in DMSO–CH₃CN (1:1, v/v) was studied. With the meta- and para- substituted compounds the additivity rule of chemical shifts was obeyed, thereby enabling increments characterizing the effects of individual substituents in monosubstituted benzenes to be determined. By employing the Smith and Proulx equation, the chemical shifts of the aromatic protons were correlated with the F, R and Q substituent constants. The values of these constants are 1.02, ?0.004 and 5.49, respectively, for the tetrazolyl substituent.     

Carbon-13 nuclear magnetic resonance spectroscopy—VII:para-substituted fluorobenzenes

C-13 and F-19 NMR spectra of seventeen para-substituted fluorobenzenes were measured and the chemical shifts as well as coupling constants with respect to substituents were analysed. The chemical shifts of the fluorine, the C₁ and the C₂ atoms were found to depend on the total electron densities. In the case of the C₃ atom, the chemical shifts seem to depend on π-electron densities rather than the total electron densities. The present calculations also indicate that the chemical shift of the C₄ atom depends mainly on σ-electron densities due to the inductive effects of substituents. The strongest factor influencing the coupling constant, ⁿJ(C? F), is also considered to be the π-electron densities on the carbon atoms. In the case of the direct couplings, ¹J(C? F), the π-bond orders are important.     

Through‐space 19F–19F spin–spin coupling in ortho‐fluoro Z‐azobenzene

We report through‐space (TS) ¹⁹F–¹⁹F coupling for ortho‐fluoro‐substituted Z ‐azobenzenes. The magnitude of the TS‐coupling constant (^TSJ_FF) ranged from 2.2–5.9 Hz. Using empirical formulas reported in the literature, these coupling constants correspond to non‐bonded F–F distances (d_FF) of 3.0–3.5 Å. These non‐bonded distances are significantly smaller than those determined by X‐ray crystallography or density functional theory, which argues that simple models of ¹⁹F–¹⁹F TS spin–spin coupling solely based d_FF are not applicable. ¹H, ¹³C and ¹⁹F data are reported for both the E and Z isomers of ten fluorinated azobenzenes. Density functional theory [B3YLP/6‐311++G(d,p)] was used to calculate ¹⁹F chemical shifts, and the calculated values deviated 0.3–10.0 ppm compared with experimental values. Copyright © 2015 John Wiley & Sons, Ltd.