Direct Investigation of Covalently Bound Chlorine in Organic Compounds by Solid‐State ³⁵Cl NMR Spectroscopy and Exact Spectral Line‐Shape Simulations

Abstract

35/37 Cl NMR spectroscopy studies of organic systems are very rare, with only a few neat liquids having been studied. [1] The lack of chlorine NMR spectroscopy data may be explained by the fact that 35 Cl and 37 Cl are quadrupolar (spin I = 3/2) and low-frequency isotopes. The quadrupole moments of the chlorine nuclei couple with the electric field gradient (EFG) tensor at the nuclei; this phenomenon is known as the quadrupolar interaction (QI). The quadrupolar coupling constant, C Q , and the quadrupolar asymmetry parameter, h Q , describe the magnitude and asymmetry of the QI. In solution, one of the consequences of the QI is fast relaxation, which means that the 35/37 Cl NMR signals for covalently bound chlorines are very broad and are of low intensity. [1] For these reasons, chemically distinct chlorine sites are very difficult to distinguish with solution NMR spectroscopy. However, in the solid state, nuclear spin relaxation is typically slower, thus enabling higher quality 35 Cl NMR spectra to be collected, at least in principle. Unfortunately, the magnitude of the QI for covalently bound chlorines is very large because of the substantial, anisotropic EFG at the Cl atom, owing mainly to its electronic configuration when it forms a chlorine-carbon bond. Conventional wisdom is that such chlorine sites cannot be studied in powders by solid-state NMR spectroscopy as the central transition (CT; m I = 1/2$À1/2) can span tens of megahertz in typical commercially available magnetic fields. For this reason, only ionic chlorides [2] and inorganic chlorides [3] have been studied, as the EFG at these chlorides is often an order of magnitude smaller than at covalently bound chlorine atoms in organic molecules. The bonding environments for these types of chlorine atoms are substantially different from the environments in those chloride-containing molecules that have been studied previously. [2, 3] A partial 35 Cl NMR spectrum for hexachlorophene has been briefly mentioned in the literature. [4] On the other hand, most of the interesting chlorine chemistry occurs when Cl is covalently bound to a carbon atom, where the chlorine atom often acts as a leaving group. Chlorine atoms are also important in many organic pharmaceuticals as well as in crystal design applications where they can form halogen bonds. [5] Recent studies show that covalently bound chlorine is also important in biological chemistry where, for example, the tryptophan 7-halogenase was found to selectively chlorinate tryptophan moieties. [6] Herein, we show that with the combination of an ultrahigh magnetic field (B 0 = 21.1 T) and the state-of-the-art WURST-QCPMG pulse sequence, [7] it is possible to acquire highquality 35 Cl NMR spectra of organic compounds that contain a covalently bound chlorine atom in powder samples in a reasonable amount of time. We have acquired 35 Cl NMR spectra of 5-chlorouracil (1); the pesticide 2-chloroacetamide (2); sodium chloroacetate (3); a,a'-dichloro-o-xylene (4); chlorothiazide (5), a diuretic pharmaceutical also k...

A Study of Transition‐Metal Organometallic Complexes Combining 35Cl Solid‐State NMR Spectroscopy and 35Cl NQR Spectroscopy and First‐Principles DFT Calculations

“…We conducted spectral simulations utilizing both WSolids and QUEST, and found that there were no substantial differences between the spectra generated by each method. This is likely because even the largest C Q magnitudes reported herein are substantially smaller than those observed by Perras et al [48] For example, the 35 Cl SSNMR spectrum of 12 was simulated with both programs, and resulting quadrupolar parameters were identical (within uncertainties, Figure S11), thereby confirming the validity of the simulations completed using WSolids. 35 Cl T 2 measurements and spectral intensity distributions: Many of the CT powder patterns observed in the 35 Cl SSNMR spectra obtained for complexes 1-14 have intensity distributions that do not match precisely with analytical simulations.…”

“…All analytical simulations shown thus far were completed using second-order perturbation theory under the high-field approximation (i.e., n 0 @ n Q , and a pure Zeeman basis set is used). Perras et al [48] recently demonstrated that the high field approximation can fail, and that the low frequency regions of 35 Cl SSNMR spectra acquired at 21.1 T (n 0 = 88.2 MHz) for a series of organochlorine compounds were not simulated correctly using perturbation theory. In this work, the values of C Q for covalently bound chlorine atoms are on the order of 70 MHz (i.e., n Q = 35 MHz).…”

“…[45] In contrast, there are very few publications regarding the application of 35 Cl SSNMR spectroscopy to systems with Cl in less spherically symmetric environments (i.e., covalently bound Cl atoms). To date, the works by Chapman and Bryce, [46] Rossini et al [47] and Perras and Bryce [48] have provided the most comprehensive structural studies of such Clcontaining systems using the variable-offset quadrupolar Carr-Purcell-Meiboom-Gill (QCPMG) [49][50][51][52][53][54][55] and WURST-QCPMG techniques. [56,57] In each, a series of bridging and/or terminal chlorine environments were investigated for a variety of different systems, including Cl-containing salts, metallocenes and organochlorine compounds.…”

Solid‐state nuclear magnetic resonance and nuclear quadrupole resonance as complementary tools to study quadrupolar nuclei in solids

“…The satellite transitions were included in the simulations, with the area corresponding to the central transitions filled in with color. Much like the case in Figure A, the line widths of the central transition of 35/37 Cl ( Q ( 35 Cl) = −81.65(80) mb, Q ( 37 Cl) = −64.35(64) mb) covalently bonded to carbon are manageable by SSNMR and also provide information on the chemical shift. As is immediately apparent however, the line widths of the central transitions of 79/81 Br ( Q ( 79 Br) = 313(3) mb, Q ( 81 Br) = 262(3) mb), and 127 I ( Q ( 127 I) = −696(12) mb) covalently bonded to carbon become prohibitively large, spanning hundreds of MHz.…”

Spin–Spin Coupling between Quadrupolar Nuclei in Solids: 11B–75As Spin Pairs in Lewis Acid–Base Adducts

“…13 As the static magnetic field strength of commercially available instruments increases, allowing faster acquisition of broad quadrupolar powder patterns, and as broadband pulse sequences are developed, 58 the acquisition of solid-state NMR spectra that fall outside of the high-field regime is becoming more practical. Recent examples of very broad quadrupolar powder patterns in solids, which were all acquired at B 0 = 21.14 T, include the 127 I NMR spectrum of SrI 2 , with a breadth of approximately 10 MHz, 59 61 Finally, a recent study we have conducted features the 121 Sb NMR spectrum of solid Ph 4 SbBr, whose central transition spans 5.5 MHz with a C Q ( 121 Sb) value of 159 MHz (ν 0 ( 121 Sb) = 215.4 MHz). 27 Note that the breadth of a quadrupolar powder pattern at a specific magnetic field strength depends not only on the magnitude of the quadrupolar interaction (i.e., values of C Q and η), but also on the spin number of the nucleus, with the total width of the powder pattern decreasing for increasing values of I.…”