ЯМР протонов: основы и применение в определении структуры молекул

NMR via protons, hydrogen 1 nuclei

Proton nuclear magnetic resonance (proton NMR, hydrogen 1 NMR, or 1H NMR) is the application of nuclear magnetic resonance in NMR spectroscopy with respect to hydrogen 1 nuclei within the molecules of a substance, in order to determine the structure of its molecules. In samples where natural hydrogen (H) is used, practically all the hydrogen consists of the isotope 1H (hydrogen 1; i. e. having a proton for a nucleus). Simple NMR spectra are recorded in solution, and solvent protons must not be allowed to interfere. Deuterated (deuterium = 2H, often symbolized as D) solvents especially for use in NMR are preferred, e. g. deuterated water, D2O, deuterated acetone, (CD3)2CO, deuterated methanol, CD3OD, deuterated dimethyl sulfoxide, (CD3)2SO, and deuterated chloroform, CDCl3. However, a solvent without hydrogen, such as carbon tetrachloride, CCl4 or carbon disulfide, CS2, may also be used. Historically, deuterated solvents were supplied with a small amount (typically 0.1%) of tetramethylsilane (TMS) as an internal standard for referencing the chemical shifts of each analyte proton. TMS is a tetrahedral molecule, with all protons being chemically equivalent, giving one single signal, used to define a chemical shift = 0 ppm. It is volatile, making sample recovery easy as well. Modern spectrometers are able to reference spectra based on the residual proton in the solvent (e. g. the CHCl3, 0.01% in 99.99% CDCl3). Deuterated solvents are now commonly supplied without TMS. Deuterated solvents permit the use of deuterium frequency field lock (also known as deuterium lock or field lock) to offset the effect of the natural drift of the NMR's magnetic field In order to provide deuterium lock, the NMR constantly monitors the deuterium signal resonance frequency from the solvent and makes changes to the to keep the resonance frequency constant. Additionally, the deuterium signal may be used to accurately define 0 ppm as the resonant frequency of the lock solvent and the difference between the lock solvent and 0 ppm (TMS) are well known. Proton NMR spectra of most organic compounds are characterized by chemical shifts in the range +14 to 4 ppm and by spin spin coupling between protons. The integration curve for each proton reflects the abundance of the individual protons. Simple molecules have simple spectra. The spectrum of ethyl chloride consists of a triplet at 1.5 ppm and a quartet at 3.5 ppm in a 3:2 ratio. The spectrum of benzene consists of a single peak at 7.2 ppm due to the diamagnetic ring current. Together with carbon 13 NMR, proton NMR is a powerful tool for molecular structure characterization.

Chemical shift values, symbolized by δ, are not precise, but typical they are to be therefore regarded mainly as a reference. Deviations are in ±0.2 ppm range, sometimes more. The exact value of chemical shift depends on molecular structure and the solvent, temperature, magnetic field in which the spectrum is being recorded and other neighboring functional groups. Hydrogen nuclei are sensitive to the hybridization of the atom to which the hydrogen atom is attached and to electronic effects. Nuclei tend to be deshielded by groups which withdraw electron density. Deshielded nuclei resonate at higher δ values, whereas shielded nuclei resonate at lower δ values. Examples of electron withdrawing substituents are OH, OCOR, OR, NO2 and halogens. These cause a downfield shift of approximately 2–4 ppm for H atoms on Cα and of less than 1–2 ppm for H atoms on Cβ. Cα is an aliphatic C atom directly bonded to the substituent in question, and Cβ is an aliphatic C atom bonded to Cα. Carbonyl groups, olefinic fragments and aromatic rings contribute sp2 hybridized carbon atoms to an aliphatic chain. This causes a downfield shift of 1–2 ppm at Cα. Note that labile protons ( OH, NH2, SH) have no characteristic chemical shift. However, such resonances can be identified by the disappearance of a peak when reacted with D2O, as deuterium will replace a protium atom. This method is called a D2O shake. Acidic protons may also be suppressed when a solvent containing acidic deuterium ions (e. g. methanol d4) is used. An alternate method for identifying protons that are not attached to carbons is the heteronuclear single quantum coherence (HSQC) experiment, which correlates protons and carbons that are one bond away from each other. A hydrogen that is not attached to a carbon can be identified because it does not have a crosspeak in the HSQC spectrum. Functional groupCH3CH2CHCH2R0.81.31.6C=C1.62.02.6C≡C1.72.22.8C6H52.32.62.9F4.34.44.8Cl3.03.44.0Br2.73.44.1I2.23.24.2OH3.33.53.8OR3.33.43.7OC6H53.84.04.3OCOR3.64.15.0OCOC6H53.94.25.1OCOCF34.04.4 CHO2.22.42.5COR2.12.22.6COOH2.12.32.6COOR2.02.32.5CONR22.02.12.4CN2.12.53.0NH22.52.73.0NR22.22.42.8NRC6H52.63.03.6NR3+3.03.13.6NHCOR2.93.33.7NO24.14.24.4SR2.12.53.1SOR2.63.1 =O (aliphatic aldehyde) 9.5=O (aromatic aldehyde) 10M H (metal hydride) 5 to 15

The integrated intensities of NMR signals are, ideally, proportional to the ratio of the nuclei within the molecule. Together with chemical shift and coupling constants, the integrated intensities allow structural assignments. For mixtures, the signal intensities can be used to determine molar ratios. These considerations are valid only when sufficient time is allowed for full relaxation of the affected signals, as determined by their T1 values. A further complication arises from the difficulty of integrating signals of very different line shapes.

If there are other NMR active nuclei present in a molecule, spin spin coupling will be observed between the hetero atoms and the protons. This occurs most frequently in compounds that contain phosphorus or fluorine, as they are both spin 1/2 nuclei of 100% abundance. For example, the 1H signals for the protons in fluoromethane are split into a doublet by the fluorine atom; conversely the fluorine 19 NMR spectrum of this compound shows a quartet due to being split by the three protons. Typical 2J coupling constants between fluorine and protons are 48 Hz or so; the strength of coupling declines to 2 Hz in 4J coupling. Even larger coupling constants may be seen in phosphines, especially if the proton is directly bonded to the phosphorus. Coupling constants for these protons are often as large as 200 Hz, for example in diethylphosphine, where the 1J P H coupling constant is 190 Hz. These coupling constants are so large that they may span distances in excess of 1ppm (depending on the spectrometer), making them prone to overlapping with other proton signals in the molecule.

Occasionally, small peaks can be seen shouldering the main 1H NMR peaks. These peaks are not the result of proton proton coupling, but result from the coupling of 1H atoms to an adjoining carbon 13 (13C) atom. These small peaks are known as carbon satellites as they are small and appear around the main 1H peak i. e. satellite (around) to them. Carbon satellites are small because only very few of the molecules in the sample have that carbon as the rare NMR active 13C isotope. As always for coupling due to a single spin 1/2 nucleus, the signal splitting for the H attached to the 13C is a doublet. The H attached to the more abundant 12C is not split, so it is a large singlet. The net result is a pair of evenly spaced small signals around the main one. If the H signal would already be split due to H–H coupling or other effects, each of the satellites would also reflect this coupling as well (as usual for complex splitting patterns due to dissimilar coupling partners). Other NMR active nuclei can also cause these satellites, but carbon is most common culprit in the proton NMR spectra of organic compounds. Sometimes other peaks can be seen around 1H peaks, known as spinning sidebands and are related to the rate of spin of an NMR tube. These are experimental artifacts from the spectroscopic analysis itself, not an intrinsic feature of the spectrum of the chemical and not even specifically related to the chemical or its structure. Carbon satellites and spinning sidebands should not be confused with impurity peaks.