NMR Spectroscopy Introduction NMR Spectroscopy is an analytical method for determining the structure of organic compounds. Specifically, NMR spectroscopy provides information about the carbon skeleton of an organic molecule. Only elements with an odd number of protons or neutrons in its nucleus can be analyzed by NMR spectroscopy. The most useful type of NMR analyses are proton (1H) and carbon-13 (13C) NMR spectroscopy (Carbon-13 is an isotope of the more naturally abundant carbon 12). We will only study proton NMR spectroscopy. In proton NMR spectroscopy, only H atoms give rise to peaks in the spectrum.

Sample Preparation Samples (both solids and liquids) for one-dimensional NMR spectroscopic analysis are usually dissolved in a . Only organic which do not contain H atoms can be used in NMR spectroscopy, otherwise peaks from the solvent will appear in the spectrum. Frequently, deuterated organic solvents are used, which means all of the H atoms of those solvents are replaced by , the 2H isotope of H, which is not detectable in NMR spectroscopy. Some common solvents that are used for NMR spectroscopic analysis are listed in Table 6.3. Compounds must be completely soluble in the solvent for NMR analysis.

Solvent Molecular Formula Carbon tetrachloride CCl4 CDCl3 Deuterated CD6O Deuterated dimethylsulfoxide (DMSO) CD6SO CD3OD

Table 6.3: Common Solvents Used for NMR Analysis

Appearance of the Proton NMR Spectrum Shown below in Figure 6.1 is a typical, one-dimensional proton NMR spectrum. (The term “spectrum” is the singular form of the word; “spectra” is the plural form of the word.) Two-dimensional spectra or NMR spectra of other atoms (i.e., 13C ) look different. For proton NMR, “peaks” originate from the baseline of the spectrum. Only the H atoms of an organic molecule give rise to peaks in a proton NMR spectrum. Peaks appear at different positions along the baseline (horizontal axis, frequency) depending on what type of H atom is responsible for giving rise to that peak. The term “resonance” is also used to describe a peak in an NMR spectrum. The Language of NMR Spectroscopy The proton NMR spectrum of ethyl acetate is given in Figure 6.1. There are three distinct peaks or resonances in the spectrum. Two of the peaks are split or have multiplicities greater than 1. The peak at 0 ppm corresponds to TMS, the internal standard and is not counted as a peak. The triplet at 1.1-1.35 ppm corresponds to the Hb of the CH2- group of ethyl acetate. The singlet has a chemical shift of 2.0 ppm, and corresponds to the Ha hydrogens of the methyl group of ethyl acetate. Finally, the quartet at 4.0-4.4 ppm corresponds to the Hc hydrogens of the other methyl group of ethyl acetate. O Hb Hb Ha C Hc COC Hc Ha Ha Hc Ethyl Acetate Figure 6.1: Typical one-dimensional proton NMR spectrum

Tetramethylsilane (TMS) or other “internal standards” are used to calibrate the x-axis of the spectrum to set the scale for the spectrum. TMS is used most frequently and always gives rise to a peak at zero. The units of x-axis of the spectrum are parts per million (ppm) or hertz (Hz). The ppm units are more commonly used and run from 1-10ppm or 1-12ppm in a typical proton spectrum. The specific ppm unit where a peak appears in the spectrum is referred to as the chemical shift of the proton(s) that give rise to that peak. The far left side of the spectrum is referred to as downfield and the far right side of the spectrum is referred to as upfield. The vertical axis is a measure of peak intensity. The area under the peak (or peak height and width) represents the relative number of H atoms that correspond to that peak.

Chemical Shift (δ) The chemical shift of a proton is the position of the peak in the NMR spectrum that corresponds to that proton. The chemical shift is the ppm unit at which the peak appears, “shifted from” the zero point defined by the TMS internal standard. The chemical shift itself is reported in ppm units. The chemical shift of a proton is dependent on what kind of atom the proton is bonded to and on the kinds of other atoms that are near to the proton. Protons can be categorized into seven chemical shift ranges. The Table 6.4 given below defines these ranges. Protons bonded to the same atom usually appear together as a single peak. Protons in the same chemical shift range may have different specific chemical shifts due to differences in environment of protons in the same range.

Range Kind of Proton 0-1.5 ppm H atoms bonded to sp3 carbons where the sp3 carbons are only bonded to other sp3 carbons and (alkanes) 1.5 - 2.5 ppm H atoms bonded to sp3 carbons where the sp3 carbon is bonded to at least one sp2 C and no heteroatoms (allylic, benzylic, α-H) 2.5 - 4.5 ppm H atoms bonded to an sp3 C that is also bonded to at least one heteroatom 4.5 - 6.5 ppm H atoms bonded to sp2 carbons of alkenes (not aromatic sp2 carbons) 6.5 - 8.5 ppm H atoms bonded to sp2 carbons of an aromatic ring 10 - 12 ppm H atom bonded to an sp2 carbon atom of the carbonyl group of an aldehyde or H atom bonded to the sp3 oxygen of a carboxylic acid. Anywhere H atom directly bonded to a heteroatom other than the oxygen atom of a carboxylic acid. Show up as a broad singlet

Table 6.4: Proton NMR Spectroscopy Chemical Shift Ranges of Various Proton Types

Multiplicity (Splitting) Peaks in a NMR spectrum do not always show up as a single peak. Peaks may appear in five ways, shown in Figure 6.2.

singlet doublet triplet quartet multiplet 1:1 1:3:1 1:2:2:1 variable

Figure 6.2: Examples of Different Types of Peak Multiplicities in Proton NMR Spectroscopy

Peaks are split into parts due to other non-equivalent H atoms that are three bonds or less away from the proton. which corresponds to the peak being split. A peak will be split into n+1 parts, where n = the # of H three bonds away. H of the same exact type are referred to as “equivalent” H (typically H bonded to the same carbon atom) and will not split each other. Peaks are referred to as singlet (one peak), doublet (two peaks), triplet (three peaks), quartet (four peaks) or multiplet (five or more peaks). An example analysis of proton multiplicities in provided below. The ratios of the peak heights or areas for these different multiplicities are very characteristic. The two peaks of a doublet appear in a 1:1 ration, the three peaks of a triplet appear as a 1:3:1 ratio, the four peaks of a qurtet appear as a 1:2:2:1 ratio. The ratio of peaks that make up a multiplet vary.

Hydrogen atoms in a molecule that are not near (near defined as 3 bonds or less) any other hydrogen atoms will appear as singlets in the proton NMR spectrum (n=0, m=0 + 1= 1, singlet). Hydrogen atoms directly bonded to heteroatoms (OH, NH etc) usually appear as singlets as well, however the shape of the peak for these H atoms is usually low and broad as opposed to tall and sharp (with the exception of carboxylic acid OH hydrogens. These are usually sharp). Sometimes, protons bonded to heteroatoms do not appear in the spectrum at all.

The proton NMR spectrum at the left has two singlets. The low, broad “singlet corresponds to an OH hydrogen of an alcohol.

Doublets appear when one H atom is 3 bonds or less away (n =1; m =1+1=2, doublet). A doublet is present in the NMR spectrum of isopropyl alcohol. The doublet corresponds to the six, equivalent H atoms of the two methyl groups labeled as Ha protons in the structure. The Ha protons are split into two parts by the one Hb proton that is 3 bonds or less aways from the Ha protons. Hc does not appear and the Hb proton appears as a multiplet (split into seven parts parts) due to the six Ha hydrogens that are 3 bonds or less away from the Hb proton.

Ha Ha Ha C Hb Ha C C OHc Ha Ha

isopropyl alcohol

Integration The relative area under each peak corresponds to the relative number of protons that correspond to that peak. Integration measures the relative areas under peaks in the same spectrum. The integration of peaks is typically provided in two ways, using integration lines or by numerical ratios. The two methods of integration are illustrated in the proton NMR spectrum of isopropyl alcohol. For the line method, the rise of the line must be measured with a ruler. The ratio of the length of the rises for each peak corresponds to the ration of different types of protons. Integration is not always provided in an NMR spectrum.