Richard F. Daley and Sally J.

Daley
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Organic Chemistry
Chapter 10

Nuclear Magnetic Resonance

10.1 Theory of Nuclear Magnetic Resonance 10.2 Shielding 478 10.3 Chemical Shift and Molecular Structure 10.4 Interpreting Proton NMR Spectra 10.5 Spin-Spin Splitting 491 10.6 Integration Signals in an NMR Spectrum 10.7 Analyzing an NMR Spectrum 503 Sidebar Magnetic Resonance Imaging 10.8 Strategy for Solving Spectral Problems Key Ideas from Chapter 10 519 475 480 484 501 511 513

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Copyright 1996-2005 by Richard F. Daley & Sally J. Daley All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the copyright holder.

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Chapter 10

Nuclear Magnetic Resonance

Chapter Outline
10.1 10.2 10.3 10.4 10.5 10.6 10.7 10.8 Theory of Nuclear Magnetic Resonance
The physical principles behind nuclear magnetic resonance

Shielding
How nearby atoms in a molecule change the observed location for the resonance signal in an NMR spectrum

Chemical Shift and Molecular Structure

Correlating the chemical shift of a proton with molecular structure

Interpreting Proton NMR Spectra

Correlating an NMR spectrum with the structure of the original molecule

Spin-Spin Splitting
Interaction of a proton at resonance with protons on adjacent carbons not at resonance

Integration of Signals in an NMR Spectrum

Determining the relative numbers of protons for each signal in an NMR spectrum

Analyzing an NMR Spectrum

Techniques for analyzing an NMR spectrum

Spectroscopic Analysis of Unknown Organic Compounds

Combining IR, NMR, and MS to deduce the structure of a unknown compound

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Objectives
Understand the molecular basis for nuclear magnetic resonance spectroscopy Know how the molecular features of a molecule affect the position of resonance for a particular proton in an NMR Be able to sketch the expected NMR for simple molecules Use spin-spin splitting along with integration to further learn about the structure of a molecule Be able to combine the information from an IR, NMR, and MS to postulate a reasonable structure for an unknown compound

The quick harvest of applied science is the usable process, the medicine, the machine. The shy fruit of pure science is Understanding. - Lincoln Barnett

hapter 10 continues the study of molecular spectroscopy techniques by investigating nuclear magnetic resonance (NMR). NMR provides information about the nuclei of the atoms in a molecule. Nuclear magnetic resonance spectroscopy is a powerful tool that chemists use to help determine the structure of molecules. The environment of the nuclei in a molecule affects the appearance and position of the signals in the NMR spectrum. A number of nuclei give rise to NMR spectra. These include 1H, 13C, 15N, 19F, and 31P. Because organic compounds contain carbon and hydrogen, organic chemists use both proton (1H) and carbon (13C) magnetic resonance. Most frequently, they use proton NMR, although carbon NMR is becoming much more widely used. Assume NMR means proton magnetic resonance, unless otherwise stated. Chapter 9 covered IR spectroscopy and mass spectrometry. IR spectroscopy provides information about the bonds in a compound and is particularly useful for the identification of functional groups. Combining IR, NMR, and MS along with chemical analysis provides sufficient information to routinely identify most unknown compounds. The goal of Chapter 9 and this chapter is to provide you with the tools

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needed to identify the structure of unknown compounds based on these three spectral types.

10.1 Theory of Nuclear Magnetic Resonance

Nuclear spin is the sum of the spin quantum numbers of the particles in the nucleus.

The magnetic moment of a nucleus is the magnetic field generated by the nuclear spin.

A nucleus with an odd atomic number and/or an odd mass number has a nuclear spin. It is the transition between nuclear spin states that the NMR spectrometer detects. Such a nucleus behaves as if it were spinning on an axis. For a proton the nuclear spin, based on the spin quantum number, has one of two possible values: +1/2 or 1 1/2 . Under ordinary circumstances, both spin states have the same energy level. The simplest example of an atom with a nuclear spin is a hydrogen atom that contains a single proton in its nucleus. Visualize a proton as a spinning sphere with a positive charge. Because the spinning movement of a charged particle generates a magnetic field (called H), a proton behaves similarly to a small bar magnet. See Figure 10.1. Chemists call this magnetic field the magnetic moment of the nucleus.

N S

Spinning proton

Bar magnet

Figure 10.1. A spinning proton generates a magnetic field called its magnetic moment. The magnetic field (H) of a proton resembles the magnetic field of a small bar magnet.

If you place a small magnet in the magnetic field of a larger magnet, the small magnet immediately aligns itself with the magnetic field of the larger magnet. This alignment is either parallel with or antiparallel to the field of the larger magnet. The external magnetic field of the larger magnet is called Ho. When you place a nucleus with a magnetic moment in an external magnetic field, as with the small
There are a variety of possible nuclear spins: 0, 1/2, 1, 3/2, etc. Any non-zero spin states all give rise to magnetic resonance spectra. In this text, we consider only the 1/2 spin states which includes 1H, 13C, 15N, 19F, 31P, and some other elements.
1

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magnet, the two spin states of the nucleus align themselves with the applied magnetic field. The +1/2 spin state aligns itself parallel to the applied field, and the 1/2 spin state aligns antiparallel with the applied field. Chemists often call the +1/2 spin state the -spin state and the 1/2 the -spin state. Because the -spin state aligns itself against the applied magnetic field, it is the higher energy state. See Figure 10.2. Typically, nearly equal amounts of both spin states are in the magnetic field.

H0

+
H

- sp in state

- sp in sta te

Figure 10.2. The nuclear spin states of a proton in the presence of an external magnetic field, H0. The magnetic field of the spin state on the left is the lower energy -spin state. The one on the right is the higher energy -spin state.

A nucleus undergoes spin flip when going from parallel to antiparallel to the external magnetic field.

A nucleus in resonance is spin flipping in time with the applied radiofrequency field.

As stated earlier, in the absence of an external magnetic field the energy levels of the two spin states are the same. If you apply an external magnetic field, the energy levels change so that one energy level is greater than the other. The difference in energy between the two spin states is directly proportional to the strength of the applied magnetic field. Still, this energy difference is quite small even in very powerful magnetic fields. For example, with a magnetic field strength of 25,000 gauss, the energy difference is only about 105 kcal/mole. This energy difference is around the energy of photons in the radiofrequency region of the electromagnetic spectrum. When photons of proper energy strike nuclei aligned with the external magnetic field of the NMR spectrometer, then the nuclei flip to the other alignment. This flip, called a spin flip, between the two spin states requires just the right combinations of magnetic field and electromagnetic radiation. A nucleus is then in resonance as it flips in time with the applied radiofrequency. The NMR spectrometer detects and records this absorption of energy. A typical student instrument has a magnetic field of 14,092 gauss and a radiofrequency of 6 x 107 Hz or 60 MHz. In research laboratories, spectrometers commonly operate at the higher radiofrequencies of 200 MHz, 300 MHz, and 500 MHz. There are two types of NMR spectrometers. One type has a stable magnetic field and

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a variable radiofrequency. The other type has a stable radiofrequency and a variable magnetic field. When using a 60 MHz instrument to look at most organic molecules, the total range for the radiofrequency is about 750 Hz, or about 0.18 gauss for the magnetic field. Figure 10.3 is a schematic diagram of an NMR instrument.
M ag net p ol es Sam pl e Ho Rad i of r eq uency r ecei ver

Pl o t t er o ut pu t

Radi o f r equ ency t r an s m i t t er

Figure 10.3. Schematic diagram of an NMR spectrometer.

Because chemists commonly use NMR spectrometers of various magnetic field strengths, they adopted a machine independent method to measure chemical shift. This method measures chemical shift as parts per million (ppm) of the applied field. Each measurement produces the same value for a given proton whether the applied field is the 14,092 gauss of the 60 MHz instrument or 46,972 gauss of the 200 MHz instrument. A chemical shift of one ppm is equal to 60 Hz, or 1.4 x 102 gauss, for a 60 MHz NMR and 200 Hz, or 4.7 x 102 gauss for a 200 MHz NMR. Figure 10.4 shows the separation of peaks with increasing magnetic field.

H0
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Figure 10.4. The energy difference between the and states increases with increasing applied magnetic field strength. This is known as the Zeeman effect.

Most student NMR instruments have a fixed radiofrequency and a variable magnetic field. The machine plots the spectrum on a special paper designed to read the chemical shift in Hz and ppm. The number of Hz in one ppm depends on the radiofrequency of the instrument. The chemical shift value in ppm stays the same if the radiofrequency was varied, or if the magnetic field was varied.

10.2 Shielding
Section 10.1 briefly examined the spin flip, or resonance, of an isolated proton if that proton were placed within an NMR spectrometers magnetic field. A proton is an isolated hydrogen nucleus, but the protons in actual organic molecules are not isolated at all. They are a part of a molecule. An organic molecule is made up of carbon atoms, heteroatoms, the electrons associated with the bonds of the atoms, and the nonbonding electrons present on some heteroatoms. The arrangement of these four molecule parts affects the resonance of the proton being considered. The protons electrons and the electrons in the adjacently bonded atoms surround the proton and partially shield it from an externally applied magnetic field. The shielding is a result of a small magnetic field generated by the movement of the electrons within the applied magnetic field. This internally generated, or induced, magnetic field always opposes the externally applied magnetic field, so chemists say the protons in the molecules are shielded from the applied magnetic field. See Figure 10.5.

A proton is shielded when electrons from adjacent atoms cause resonance to occur at higher field strength than it otherwise would.

Ha

Hb

Ha

Hb

C C
(a)

C C
(b)

Figure 10.5. The magnetic field of non-equivalent adjacent protons affects the position of resonance. (a) The magnetic field of proton Ha shields proton Hb. (b) The magnetic field of proton Ha deshields proton Hb.

Because of the shielding, the effective magnetic field reaching the proton from an externally applied magnetic field is less than the amount that would reach the proton if it was not shielded. Thus, a

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shielded proton requires a greater amount of applied magnetic energy for resonance to occur. In a 60 MHz spectrometer, an unshielded proton absorbs at 14,092 gauss. For a proton shielded by 0.5 gauss, the magnetic field at the proton then becomes 14,091.5 gauss. You must increase the applied field to 14,092.5 gauss to bring this proton into resonance. See Figure 10.6.

Sh ie ld in g

H0

H 0 = 14,092

H 0 = 14 , 09 2

H 0 = 14,092.5

Figure 10.6. A bare, or isolated, proton is in resonance in a 14,092 gauss field at 60 MHz (left). A proton shielded by 0.5 gauss does not resonate at 14,092 gauss (center), but it does at 14,092.5 gauss (right).

A proton, as well as the nuclei of all kinds of atoms that resonate, requires a specific amount of applied magnetic energy to spin flip. Each proton that is surrounded by a different set of atoms within a molecule has a different amount of shielding. The differences in shielding are due to different magnetic environments in the molecule. The factors that affect the magnetic environment include nonbonding electrons, the electronegativity of adjacent atoms, and electron circulation. Thus, the resonance of each of these protons occurs at a different combination of magnetic field and radiofrequency. For example, consider the protons in methanol. The electronegative oxygen withdraws electron density from its proton, giving it less shielding than the methyl protons. Therefore, the hydroxyl protons absorb at a lower magnetic field than the methyl protons.

H More shielded H H C OH

Less shielded

The number of absorptions in an NMR spectrum tells how many different types of hydrogens a molecule contains. The amount of shielding for each NMR signal also allows the chemist to deduce the structural features of the molecule in the region of each of the protons.

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This information from an NMR spectrum is particularly valuable when determining the carbon skeleton of a molecule.

10.3 Chemical Shift and Molecular Structure

Chemical shift is the measure of the amount of shielding possessed by a proton as a result of the induced magnetic fields from the electrons belonging to the surrounding atoms.

Shielding produces the variations in the positions of the absorption peaks in an NMR spectrum. These variations result in changes in the chemical shift of the protons. Because the induced magnetic fields of protons are small in relation to the applied magnetic field, an absolute measurement scale is impractical to use. Instead, the amount of shielding, or chemical shift, is measured relative to a standard substance. There are two possible types of standards substances: external where the substance is measured separately from the sample and internal where the substance is added to the sample. Tetramethylsilane, (CH3)4Si, abbreviated as TMS, is used as the internal standard substance. In TMS, the silicon shields the methyl protons more than almost any other organic compound. TMS does not react with the compound under study and, when the spectrum is completed, the TMS evaporates easily. All the hydrogens in TMS are equivalent so it gives only one peak. The position of TMS on an NMR spectrum is always assigned a value of zero.

CH 3 H3C Si CH 3 CH 3
Tetramethylsilane (TMS)

Downfield is lower applied magnetic field.

Upfield is higher applied magnetic field.

Most student NMR spectrometers operate at 60 MHz, so this book uses only spectra recorded at 60 MHz, unless labeled otherwise. Figure 10.7, an NMR spectrum of methanol, shows two signals for the methanol and one signal for the TMS. The TMS signal occurs at 0.0 ppm. The methyl protons absorb at 203 Hz (0.048 gauss) downfield from the TMS signal. This absorption is called downfield because the magnetic field required for resonance to occur in methyl protons is lower than for the TMS protons. The methyl protons absorb upfield from the hydroxyl proton because methyl resonance requires a higher magnetic field than does a hydroxyl resonance. The hydroxyl protons absorb 285 Hz (0.067 gauss) downfield from TMS. The chemical shifts are 3.4 ppm for the methyl protons and 4.8 ppm for the hydroxyl proton.

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HO CH 3

10 600

9 500

7 400

5 300

4 200

2 100

0 0

ppm ( ) Hz

Figure 10.7. A 60 MHz NMR spectrum of 10% methanol in CDCl3. The methyl protons absorb at 3.4 ppm and the hydroxyl proton at 4.8 ppm.

Deshielding moves the resonance of the affected protons downfield from where resonance occurs when the molecule does not contain an electronegative substituent.

Within a molecule, an electronegative substituent affects the resonance of nearby protons by pulling the electrons toward itself and decreasing the amount of shielding felt by the protons. Chemists call this electronegative pull deshielding. Deshielding influences protons on the carbon adjacent to the electronegative functional group and, to a much smaller extent, the second carbon. Figure 10.7 shows the deshielding effects of the electronegative oxygen atom on both the methyl and the hydroxyl groups. The chemical shift of a methyl group in a hydrocarbon is 0.9 ppm, so the oxygen has deshielded the methyl hydrogens in methanol by 2.5 ppm. Other electronegative atoms besides oxygen produce similar deshielding effects. Chlorine, for example, causes a chemical shift of 3.1 ppm for the methyl protons in methyl chloride. This shift is reasonable because chlorine has a slightly lower electronegativity than oxygen so it exerts a smaller deshielding affect. Table 10.1 lists the chemical shifts of various methyl substituted electronegative groups showing the correlation of electronegativity with the chemical shift that results from deshielding.
Compound CH3X (CH3)3N (CH3)2O CH3F CH3Cl CH3Br CH3I Electronegativity of X 3.1 3.5 4.1 2.8 2.7 2.2 Chemical Shift (in ppm) for the CH3 2.2 3.3 4.3 3.1 2.7 2.2

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CH3CH3 CH3H

2.5 2.2

0.9 0.2

Table 10.1. Variation of chemical shift of a methyl group with electronegativity of the heteroatom X.

When a carbon contains more than one electronegative substituent, the deshielding effects are almost additive. Each additional electronegative atom causes a similar, though slightly smaller, deshielding effect. The chemical shift data for the various chlorinated derivatives of methane shows this additive effect. CH3Cl 3.1 ppm CH2Cl2 5.3 ppm CHCl3 7.3 ppm

Vinyl and aryl compounds provide much less shielding for their protons than do alkanes. Peaks appear at 7.2 ppm for benzene protons, 5.3 ppm for ethene protons, and 0.9 ppm for ethane.
H H H H C H H Benzene 7.2 ppm H H C H H H H C H H C H H

Ethene 5.3 ppm

Ethane 0.9 ppm

Anisotropic shielding caused by the nonuniform magnetic field in the vicinity of a bond.

The magnetic field internally induced by electrons is strong enough to deshield vinyl and aryl protons. The circulation of the electrons in the bonds causes the internal magnetic field. The three conjugated bonds of benzene interact to produce a ring of current and an even stronger induced magnetic field than does a compound with only one double bond. At the center of the ring, the induced field opposes the external field; however, outside the ring, the induced field reinforces the applied field. The deshielding of the protons is caused by anisotropic shielding. Figure 10.8 shows this effect in benzene.

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H H H

H H H

H0
Figure 10.8. The induced magnetic field of the electrons in benzene reinforces the applied field where the protons are located. This is an example of anisotropy in benzene.

Because the bonds of alkenes and arenes deshield their protons, you might expect an even larger amount of deshielding in alkynes because a triple bond has two bonds. However, just the opposite occurs. Acetylenic protons absorb around 2.5 ppm compared to 5 - 6 ppm for alkenes and 7 - 8 ppm for arenes. With alkynes the two bonds form a cylinder of electron density around the CC bond. The axis of the induced magnetic field is aligned parallel to the CC bond of the triple bond, placing the adjacent protons in a region where the induced field opposes the external field. This is another effect of the anisotropy of the magnetic fields around a bond. As a result, the protons are shielded, as shown in Figure 10.9.

H C

H0

Figure 10.9. The acetylenic triple bond aligns itself with the external magnetic field. As the electrons circulate, they create an induced magnetic field. The protons lie along the axis of the induced magnetic field within the area where the induced magnetic field opposes the external magnetic field.

10.4 Interpreting Proton NMR Spectra

An NMR spectrum provides four types of information: 1) the position (energy) of the signals, 2) the number of signals present, 3)

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the intensity of the signals, and 4) the multiplicity (splitting) of the signals. You must use all four of these types of information to interpret NMR spectra. This section covers the position and number of signals. The next two sections cover the signal intensity and splitting. Protons with different chemical shifts are magnetically and chemically nonequivalent. Each nonequivalent proton produces a separate NMR signal. For example, the NMR spectrum in Figure 10.10 shows the protons in the two methyl groups in methyl acetate. Although each of the three protons in each methyl group has the same magnetic environment, the two methyl groups have different environments. Therefore, each set of protons experiences a different induced magnetic field, and each set resonates at a different applied magnetic field. The difference shows up in their signals: one appears at 3.7 ppm and the other at 2.1 ppm.
2.1 ppm O CH3 C O CH3 3.7 ppm

Methyl acetate

The methyl group attached to oxygen is more deshielded, so it appears further downfield from TMS at 3.7 ppm.

O CH3COCH3

1 0

ppm ( )

6 0 0

5 0 0

4 0 0

3 0 0

2 0 0

1 0 0

H z

Figure 10.10. The NMR spectrum of methyl acetate (CH3COOCH3).

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The environment of a proton determines its chemical shift. Each atom in the molecule contributes a characteristic amount of shielding to the total amount of shielding a particular proton experiences. The amount of shielding that a particular atom contributes is relatively constant for any molecule containing that atom. Figure 10.11 shows the general regions of a typical NMR spectrum where certain types of protons resonate. The OH and NH bonds tend to vary widely over a range of the spectrum based on their concentration. Higher concentrations tend to produce more deshielding because of hydrogen bonding. The proton on a carbonyl group of aldehydes is subject to the same conditions as those on a double bond as well as the electron-withdrawing effect of the oxygen. Their signals appear around 9.5 ppm. Signals for acid protons on a carboxylic acid appear above 10 ppm.
COOH (12.5 - 11 ppm) RCHO ArH ArOH C C H ArNH2 C CH

ROH RNH2 Alkyl Groups

10 600 9 500 8 7 400 6 5 300 4 200 3 2 100 1 0 0 ppm ( ) Hz

Figure 10.11. Regions where different types of protons resonate in the NMR.

Alkyl groups show a wide range of positions because they are affected by the functional groups adjacent to them. For example, consider the effect of a chlorine atom on the protons bonded to the same carbon as the chlorine. A methyl group in a hydrocarbon appears at 0.9 ppm, but in methyl chloride it appears at 3.2 ppm. The difference between the two is 2.3 ppm.
CH3CH3 0.9 ppm CH3Cl 3.2 ppm

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A methylene group appears at 1.3 ppm in a hydrocarbon and at 3.6 ppm in ethyl chloride. The difference is again 2.3 ppm.
CH3CH2CH3 1.3 ppm CH3CH2Cl 3.6 ppm

A methine group appears at 1.6 ppm in a hydrocarbon and at 3.9 ppm in 2-chloropropane. Again the difference is 2.3 ppm.
CH3 CH3CHCH3 1.6 ppm CH3 CH3CHCl 3.9 ppm

The shielding constant is a measure of how much a group affects the resonance position of adjacent protons.

The change in resonance position of 2.3 ppm is the characteristic amount of shielding of a chlorine atom. Chemists call this constant amount of shielding the shielding constant. Table 10.2 lists the base values of the CH, CH2, and CH3 groups. Group CH CH2 CH3 Base value 1.6 1.3 0.9

Table 10.2. Base values for the CH, CH2, and CH3 groups.

The shielding effects of an atom primarily affect the protons bonded to the same carbon as itself. However, atoms with larger shielding constants also shield the protons on adjacent carbons. This shielding is much smaller because the protons are farther away. For example, the methyl group in ethyl chloride appears at 1.5 ppm,
CH3CH2CH3 0.9 ppm CH3CH2Cl 1.5 ppm

which is only 0.6 ppm downfield from a methyl group in a hydrocarbon (0.9 ppm). Thus, the shielding constant for chlorine in adjacent bonds is 0.6 ppm and is called the shielding constant. Table 10.3 lists both the and the shielding constants for a variety of functional groups. Functional Group Shielding Constant Shielding Constant

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Functional Group

C C C C Ph F Cl Br I OX (X = H, R) OX (X = Ph, C C O SX (X = H, R)

O)

C N
NX2 (X = H, R) NO2

Shielding Constant 0.7 0.8 1.3 3.3 2.3 1.8 1.3 2.4 2.9 1.2 1.1 1.2 1.4 3.2

Shielding Constant 0.1 0.2 0.3 0.7 0.6 0.9 0.9 0.3 0.4 0.4 0.4 0.3 0.2 0.7

Table 10.3. A table of and shielding constants for a variety of functional groups.

Use the data in Table 10.2 and 10.3 either to predict the position or to confirm the identification of the signals in an NMR spectrum. These numbers do have a limitation: they do not cover all the possible arrangements of atoms in a molecule. Although the numbers are usually within 0.2 ppm for the shielding constants, they can be as much as 0.6 or 0.7 ppm in error. This is especially true when two or more shielding groups affect the position of a proton. The larger the number of functional groups, the larger the potential error. Calculating proton positions is helpful when identifying an unknown. For example, by using the numbers in Tables 10.2 and 10.3, you can calculate predicted positions of the protons in methyl acetate CH3COOCH3. Here is the calculation of the position for the CH3 group adjacent to a carbonyl group. 0.9 for the CH3 1.2 constant for carbonyl 2.1 ppm This number agrees with the observed position of 2.1 ppm as shown in the spectrum in Figure 10.10. The other CH3, which is attached to an sp3 hybrid oxygen, has the following calculated position. 0.9 for the CH3 2.9 constant for COO group 3.8 ppm This number agrees very well with the observed 3.7 ppm.

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The following example of 3,3-dimethyl-2-butanone shows the effects of shielding.

CH3 C CH3 H3C C H3C O

Again, using the information in Tables 10.2 and 10.3, calculate the position of the CH3 adjacent to the carbonyl. 0.9 base position of methyl groups 1.2 constant for carbonyl groups 2.1 ppm. The other three CH3 groups are magnetically equivalent and are to the carbonyl. The shielding constant for the carbonyl group is 0.4 ppm, so the predicted positions of these methyl groups is 1.3 ppm: 0.9 base position of methyl groups 0.4 constant for carbonyl groups 1.3 ppm The signals in the spectrum appear at 2.2 and 1.3 ppm, respectively, as shown in Figure 10.12.

O (CH 3 )3 CCCH 3

1 0

ppm (

6 0 0

5 0 0

4 0 0

3 0 0

2 0 0

1 0 0

H z

Figure 10.12. The NMR spectrum of 3,3-dimethyl-2-butanone.

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Exercise 10.1 Predict the number of NMR signals and their locations for each of the following compounds. a) 1-Propanol c) Ethyl propanoate e) Hexane g) 2,3-Dimethyl-2-butene Sample solution b) 1,4-Dichlorobutane is symmetrical between C2 and C3, so it has only two resonance signals. ClCH2CH2CH2CH2Cl The position of the resonances of the protons on the carbons bearing the chlorine atoms is 1.3 + 2.3 ppm = 3.6 ppm. The protons on the adjacent carbons experience only the shielding and so the resonance is 1.3 + 0.6 ppm = 1.9 ppm. The positions of resonance in the actual spectrum are 3.6 and 2.0 ppm respectively. The shielding constants apply only to protons bonded to sp3 hybrid carbons. Although substituent groups also affect vinyl and aromatic protons, they do so to a much smaller extent due to the strong deshielding of the electrons. Protons bonded to a double bond usually appear between 4.6 and 6 ppmtypically about 5.3 ppm. Electron-donating groups shield those protons in an amount proportional to the electron density of the group. Typically, this amount is in the range of 0.3 to 0.5 ppm. Conversely, an electron-withdrawing group deshields those protons in an amount proportional to the strength of the electron-withdrawing power of the group. Typically, this deshielding is in the range of 0.3 to 1.5 ppm. Chapter 14 covers this topic in greater length. Arenes also show the same type of effects toward donating or withdrawing groups on the ring, as do alkenes. These effects are due to conjugation, so the substituent affects only those protons bonded ortho or para to itself. Chapter 16 covers this topic in greater length. The shielding or deshielding of the ortho and para protons relative to the meta protons usually allows you to infer the general class of the substituent. Meta protons appear at, or near, 7.3 ppm. An electron-withdrawing group deshields the ortho or para protons, but an electron-donating group shields the ortho or para protons. This effect changes the position of the ortho or para signals by 0.2 to 1.0 ppm. For example, the ortho and para protons of benzoic acid appear b) 1,4-Dichlorobutane d) 2,2-Dibromobutane f) Toluene (methylbenzene) h) N-Methylethanamine

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at 8.2 ppm, and those of phenol appear at 6.8 ppm. The meta protons appear at 7.5 and 7.2 ppm respectively.
O OH OH H 8.2 ppm H H 7.5 ppm 8.2 ppm H 6.8 ppm H H 7.2 ppm

6.8 ppm

Exercise 10.2 Predict the number of resonance signals and their locations for each of the following compounds. Only approximate locations for vinyl and aryl protons are possible. a) 2-Butene c) Nitrobenzene e) 1-Phenyl-1-propene Sample solution c) Nitrobenzene has two absorptions in the NMR. The nitro group is an electron-withdrawing substituent, so one signal is near 8 ppm and the other at 7.2 ppm. b) Methyl benzoate d) Phenyl butanoate f) 1-Butene

10.5 Spin-Spin Splitting

The NMR spectra of methanol, methyl acetate, and 3,3dimethyl-2-butanone, which you examined earlier, all have one single sharp absorption signal for each type of proton. It turns out, however, that protons giving a single absorption signal are the exception rather than the rule. Usually, instead of a singlet, each signal appears as a collection of absorption signals called peaks. A single absorption signal can be split into two peaks (a doublet), three peaks (a triplet), four peaks (a quartet), etc. Chemists call the splitting of NMR signals spin-spin splitting. Thus, a signal for a proton with three adjacent protons splits into a quartet. For example, look at the spectrum of 1,1dichloroethane (Figure 10.13). The spectrum has three peaks: the TMS peak at 0.0 ppm, the CH peak at 5.9 ppm, and the CH3 peak at 2.1 ppm. The CH is adjacent to the three hydrogens of the CH3 group, so its signal splits into a quartet. The CH3 group is adjacent
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A singlet is an NMR absorption signal with only one absorption. A peak is one or more absorptions making up the signal for a proton in an NMR spectrum. A doublet (2), triplet (3), quartet (4), etc. describes a resonance signal split into a collection of peaks. Spin-spin splitting is the process that splits an NMR signal into multiple peaks.

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to the single hydrogen of the CHCl2 group, so its signal splits into a doublet.

Cl2HC

CH3

1 0

ppm ( )

6 0 0

5 0 0

4 0 0

3 0 0

2 0 0

1 0 0

H z

Figure 10.13. The NMR spectrum of 1,1-dichloroethane. Spin-spin splitting produces a quartet for the methine proton and a doublet for the methyl group.

Vicinal protons are protons attached to adjacent carbons.

The magnetic fields of adjacent protons cause spin-spin splitting. For example, all three protons in the methyl group of 1,1dichloroethane are equivalent and all have the same chemical shift; thus, you would expect them to produce one peak. However, because of the magnetic moment of the vicinal proton in the CHCl2 group, their signal splits into two lines. You have now studied three types of magnetic fields that influence protons. They are the external magnetic field, the induced fields of any shielding substituents, and the magnetic fields of adjacent protons. Thus, each type of proton in a molecule resonates at a different location in the NMR spectrum. Return to Figure 10.13 and assume that the spectrometer is scanning the region of the spectrum where methyl protons appear. Recall from Section 10.1 that when an external magnetic field is applied to a compound, the protons align themselves with that applied magnetic field with approximately half of the protons aligning themselves parallel to the applied magnetic field and the other half aligning themselves antiparallel to the applied magnetic field. Thus, in approximately half of the 1,1-dichloroethane molecules, the methyl protons are under the influence of the methine protons with their magnetic moment parallel to the applied field, and the other half are under the influence of the methine protons with their magnetic moment antiparallel to the applied field.

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When the magnetic moment of the methine proton is aligned parallel to the applied magnetic field it exerts a slightly stronger total magnetic field over the methyl protons. Thus, it effectively deshields the methyl protons, absorbing radio frequency energy at a lower external magnetic field. When the magnetic moment of the methine proton is aligned antiparallel to the external magnetic field it shields the methyl protons. They absorb radio frequency energy at a higher external field. Figure 10.14 shows the effects of an applied magnetic field.
Chemical Shift of H b

Cl H b Cl Hb
Reinforces Field

Cl H b Hb Cl Hb
Opposes Field

Hb

H 0 Vector
Increas ing H 0
Figure 10.14. When the vicinal proton is aligned with the applied magnetic field, it deshields Hb; when aligned against the field, it shields Hb.

Spin-spin splitting is a reciprocal property in that the protons on two vicinal carbons split each other. You observed this in 1,1dichloroethane. The methyl protons split the signal for the methine proton into a quartet, and the methine proton splits the signal for the methyl protons into a doublet. Figure 10.15 shows the possible spin states of the methyl protons.

Ho vector Increasing Ho
Figure 10.15. There are eight possible combinations of nuclear spins for the three methyl protons in 1,1-dichloroethane. These represent four different magnetic field

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strengths with a ratio of 1:3:3:1. The arrow pointing up is parallel to the applied field and the arrow pointing down is antiparallel.

The arrangement of the magnetic moments of the three hydrogens of the methyl group, as shown in Figure 10.15, produces four signals in a ratio of 1:3:3:1. At one extreme of the arrangement, the three protons align themselves parallel to the external magnetic field. At the other extreme, they align themselves antiparallel to the external field. Between the two extremes there are two groups of three. In the first group of three, two protons align themselves parallel with the external field, and the other aligns itself antiparallel to the external magnetic field. In the second group of three, one proton aligns itself parallel to the external magnetic field, and the other two align themselves antiparallel to the external magnetic field. This arrangement produces a quartet in the NMR similar to Figure 10.16.

Chemical shift of the methine group

Figure 10.16. These eight combinations, as shown in Figure 10.15, cause the splitting of the signal of the CHCl2 group into a quartet. The areas of the peaks are in a 1:3:3:1 ratio seen in Figure 10.15.

A multiplet is a NMR signal that is split into multiple peaks by spinspin splitting.

This analysis of spin-spin splitting patterns extends to more complicated systems than the above example. Here is a simple rule that allows you to predict spin-spin splitting patterns. The number of peaks into which the signal for a particular proton splits equals the number of vicinal protons plus one. Table 10.4 gives the relative areas of these multiplets. These relative areas are determined by an analysis like that shown in Figure 10.15. The table of relative areas is known as Pascals triangle.
Number of equivalent protons causing splitting 0 Number of peaks in the multiplet 1 (singlet) Intensities of the lines in the multiplet 1

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Number of equivalent Number of peaks in the Intensities of the lines in protons causing splitting multiplet the multiplet 1 2 (doublet) 1 1 2 3 (triplet) 1 2 1 3 4 (quartet) 1 3 3 1 4 5 (quintet) 1 4 6 4 1 5 6 (sextet) 1 5 10 10 5 1 6 7 (septet) 1 6 15 20 15 6 1 Table 10.4. Splitting patterns and relative peak intensities of common multiplets.

CH3CH2Br

1 0

ppm ( )

6 0 0

5 0 0

4 0 0

3 0 0

2 0 0

1 0 0

H z

Figure 10.17. The NMR spectrum of bromoethane shows the spin-spin splitting pattern produced by a typical ethyl group.

Canting is signal dissymmetry due to the proximity of two signals that are splitting each other. The spectrum of 1,1dichloroethane is in figure 10.13, page 000.

The triplet and quartet in the spectrum of bromoethane (Figure 10.17) are not symmetrical. Signal dissymmetry commonly occurs in NMR spectra and helps to determine which protons are splitting each other. In general, the stronger signals are on the side of the multiplet closest to the signal responsible for the splitting. Canting, the term used to describe signal dissymmetry, is more pronounced when the two signals are closer together. The ethyl group pattern, as shown in Figure 10.18, is an example of this phenomenon. Canting also occurs in the spectrum of 1,1-dichloroethane.

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Figure 10.18. The peaks in a multiplet often point toward the absorption of the protons that cause the splitting. The two signals in the ethyl splitting pattern from bromoethane point toward each other.

An important characteristic of spin-spin splitting is that protons having the same magnetic environment do not split each other. For example, benzene gives only one single peak in the NMR spectrum, even though there are several possible sets of vicinal protons. It gives only one peak because all the protons are equivalent to each other, and they all have the same chemical shift. Exercise 10.3 Sketch the appearance of the NMR spectra of the following compounds. Show how many signals you would expect to find, the location of these signals, and how many peaks each signal splits into. a) 1,2-Dichloroethane c) Diisopropyl ether e) Ethyl acetate Sample solution a) All the protons in 1,2-dichloroethane are chemically equivalent and thus have the same chemical shift. Because chemically equivalent protons do not split each other, the spectrum should show a singlet at the following calculated position. 1.3 ppm for base 2.3 ppm for Cl 0.6 ppm for Cl 4.2 ppm b) 1,1,2-Trichloroethane d) p-Diethoxybenzene f) C6H5CH(CH3)2

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Magnetic coupling is the interaction of protons on adjacent atoms that results in spin-spin splitting. Geminal protons are protons on the same carbon. Geminal splitting is spin-spin splitting between geminal protons that are not equivalent. The coupling constant is the characteristic interval between adjacent peaks in a multiplet. The NMR spectrum of 1,1-dichloroethane is in Figure 10.13, page 000.

The range of magnetic coupling is usually limited to protons on adjacent carbons. Protons separated by more than three bonds seldom produce spin-spin splitting because protons transmit their splitting information through the electrons in the bonds between the nuclei rather than through space. Geminal protons are normally equivalent, thus they do not usually split one another. In cases where they are not equivalent, splitting, called geminal splitting, occurs. Sets of magnetically coupled protons have a characteristic spacing between adjacent pairs of peaks in a multiplet. This spacing, called the coupling constant, is represented by the symbol J. The coupling constant has the same value, in Hz, for any magnetic field strength. The coupling constant for 1,1-dichloroethane is approximately 7 Hz. Thus, the interval between the two peaks of the methyl doublet is approximately 7 Hz, as is the distance between any adjacent pair of peaks in the methine quartet. Table 10.5 lists some typical coupling constants.
Molecular Fragment Approximate coupling constant, J. Molecular Fragment Approximate coupling constant, J.

H C C H H C C H H C C H
C H H
7 Hz

C H
(In rigid systems)

12 Hz

10 Hz

H C C H
H H

2 Hz

15 Hz

2 Hz

H
6 Hz

C C

C H

2 Hz

O C C H H H
C C
8 Hz 3 Hz

C C H

C H

1.5 Hz

C H

2 Hz

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Table 10.5. Typical values of proton coupling constants. Included in this table are some 2J and 4J coupling constants (right column) as well. See below for a discussion of the right column constants.

Spin-spin splitting occurs in all cases when the protons on adjacent carbon atoms have different magnetic environments. An exception to this is where conformational changes take place faster than the time frame for measuring an NMR spectrum. For example, cyclohexane has two sets of protonsaxial and equatorial. Each of these sets of hydrogens is in a different magnetic environment.

H H H

H H

H H H H H H

Equatorial hydrogens of cyclohexane

Ring flips in cyclohexane is introduced in Section 3.6, page 000.

Axial hydrogens of cyclohexane

As you may recall, these two sets of hydrogens are exchanged via a ring flip. This ring flip occurs at a higher rate than the time frame for measurement on an NMR spectrometer. Thus, cyclohexane gives rise to a single peak in the NMR spectrum. To observe separate signals for the axial and equatorial hydrogens, the rate of ring flip must be slowed by cooling the sample or the time frame for measurement of the NMR must be shortened by increasing the magnetic field and radio frequency of the instrument. However, in most cases where the protons readily exchange with the protons on another atom, splitting does not occur. Protons on atoms that hydrogen bond, particularly oxygen or nitrogen, usually are not split even though there is a proton on an adjacent atom. They arent split because protons involved with hydrogen bonding are constantly being exchanged and thus are not in the same magnetic environment long enough to be split by any adjacent protons. This hydrogen bonding exchange significantly broadens many, but not all, such peaks in the NMR. Figure 10.19 shows the NMR spectrum of 2propanol. The signal at 3.1 ppm is the OH peak that illustrates this signal broadening.

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CH3CHCH3 OH

1 0

ppm ( )

6 0 0

5 0 0

4 0 0

3 0 0

2 0 0

1 0 0

H z

Figure 10.19. The NMR spectrum of 2-propanol showing signal broadening at 3.1 ppm due to proton exchange of the OH protons.

Exercise 10.4 Draw the NMR spectra you would expect for each of the following compounds. a) 4-Methylmethoxybenzene b) 2-Methylbenzoic acid c) 1-Bromo-2-methylpropane d) 2-Butanone e) trans-3,3-Dimethyl-1-phenyl-1-butene f) Chloromethyl ethyl ether Sample solution d) 2-Butanone is a ketone with ethyl and methyl groups on either side of the carbonyl group. The position of the methyl group (a singlet) is 0.9 + 1.2 ppm = 2.1 ppm. The ethyl group has the CH2 at 1.3 + 1.2 = 2.5 ppm and the CH3 at 0.9 + 0.4 ppm = 1.3 ppm. The signal for the CH2 of the ethyl group splits into a quartet and the signal for the CH3 of the ethyl group splits into a triplet. The coupling constant for the ethyl group is about 7 Hz. Spin-spin splitting becomes more complicated when two or more magnetically non-equivalent protons split one proton. In most of these cases, the n + 1 rule for predicting splitting patterns fails. Consider Figure 10.20, which shows a single proton being split by two adjacent magnetically non-equivalent protons. In Figure 10.20 (a), one proton has a coupling constant of 8 Hz and the other a coupling

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constant of 6 Hz. Note that while there are two adjacent protons, the signal in the NMR has four linesa pair of doublets. The n + 1 rule predicts that there would be three lines from the two adjacent protons. Because the coupling constants are different, a pair of doublets is produced instead. Figure 10.20 (b) shows the effect of having J1 = 8 Hz and J2 = 11 Hz. It shows a pair of overlapping doublets.

J1 = 8 Hz

J1 = 8 Hz

J2 = 6 Hz J2 = 6 Hz

J2 = 11 Hz

J2 = 11 Hz (b)

(a)

Figure 10.20. An analysis of the splitting pattern for a single proton (a) where J1 = 8 Hz and J2 = 6 Hz and (b) where J1 = 8 Hz and J2 = 11 Hz.

Exercise 10.5 An important, but complex, splitting pattern is that of the vinyl group (CH2=CH). This common pattern is one you should learn to recognize. Using the values Jgeminal = 2 Hz, Jcis = 10 Hz, and Jtrans = 15 Hz as well as the chemical shifts shown below, draw the splitting patterns for each of the three protons on the vinyl group. Please take care in drawing this splitting pattern to scale.

4.6 ppm H

5.6 ppm H R

H 4.9 ppm
The right hand column in Table 10.5 shows the coupling constants between hydrogens that are not vicinal. These couplings include two geminal couplings as well as several couplings where the

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protons are on more distant carbons. The geminal couplings are both for rigid molecules which change conformations more slowly than the time frame for the NMR spectrum, if at all. More distant couplings generally have bonds between the protons that split each other.

10.6 Integration of Signals in an NMR Spectrum

The area under an NMR signal, not its height, is proportional to the number of hydrogens giving rise to that signal. For example, Figure 10.20 shows that the spectrum of 3,3-dimethyl-2-butanone has two singlets. One of these singlets comes from a single methyl group; the other comes from three methyls of the tert-butyl group. The area under the single methyl group signal is one third of the area that is under the signal for the three methyl groups. Therefore, the ratio of the number of hydrogens is 1:3. An NMR spectrometer has an integrator that computes the areas under the signals. By using the trace produced by the integrator, chemists determine the relative numbers of hydrogens represented by each signal in the spectrum. In Figure 10.20, note that the integration does not show that 3,3-dimethyl-2-butanone has three methyl hydrogens and nine hydrogens on the tert-butyl group. It simply indicates that there are three times as many hydrogens represented by the peak at 1.3 ppm as by the peak at 2.2 ppm.

An integrator is a device that computes the areas under the signals in an NMR spectrum.

O ( CH 3 ) 3 CCCH 3

4.5 units

1.5 units

10 600

9 500

7 400

5 300

4 200

2 100

0 0

ppm ( ) Hz

Figure 10.20. Integrated NMR spectrum of 3,3-dimethyl-2-butanone. As it passes over a signal, the integrator (upper trace) rises by an amount that is proportional to the area under the signal.

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Exercise 10.6 Match the following compounds with the spectra shown below. Assign the signals in the spectra to the specific protons they represent in the molecular structure. 4-Nitrotoluene 3-Ethylphenol a) 2-Methyl-3-butyn-2-ol 1,3-Dibromopropane 2-Chloropropane Oxacyclobutane

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b)

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c)

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Sample solution b) 4-Nitrotoluene. The doublet at 8 ppm arises from the protons adjacent (ortho) to the nitro group on the ring. The doublet at 7.2 ppm arises from the protons adjacent to the methyl group. The peak at 2.4 ppm arises from the methyl group protons.
2.4 ppm CH3 H H 7.2 ppm

H NO2

8.0 ppm

4-Nitrotoluene

10.7 Analyzing an NMR Spectrum

When beginning the interpretation of an NMR spectrum, it's easy to get bogged down in the minor details. Before looking at spinspin splitting, or canting, or the details of calculating the positions of peaks, make some tentative identifications of the types of molecular features present. The following rules may help you do this:

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1. Any broadened singlet is an OH or NH group. If the peak is deshielded above 10 ppm, the compound is almost certainly a carboxylic acid. The absence of a broadened peak is not evidence for the absence of an OH or NH proton. Sometimes a peak is so broadened that is does not appear above the baseline of the spectrum. Adding a drop of D2O to the NMR sample will make the OH and many NH bonds disappear through proton exchange. 2. An absorption between 9 and 10 ppm is an aldehyde. 3. Absorptions near 7 ppm suggest the presence of an aromatic ring. When the signal is closer to 8 ppm, the ring has an electron-withdrawing group (e.g., NO2 or CHO) bonded to it. When the signal is closer to 6.5 ppm, the ring has an electrondonating group (e.g., OH or NH2) bonded to it. 4. Absorptions in the 5 to 6 ppm range are most likely vinyl protons. Use coupling constants to differentiate between the cis and trans isomers. 5. Peaks in the 3 to 4 ppm range indicate protons bonded to a carbon that also bears an oxygen or a halogen. 6. A sharp singlet, or a peak with coupling constants of about 2 Hz, at 2.5 ppm suggests a terminal alkyne. 7. Signals at 2 to 2.5 ppm are protons on a carbon adjacent to an sp2 hybridized carbon, a carbon bonded with double bonds, or a carbonyl. 8. Signals below 2 ppm usually indicate sp3 hybridized hydrocarbon sections of the molecule. As you use these rules, keep in mind that they probably will not completely solve a spectrum, but they will usually get you started in the right direction. Their goal is to give you a simple method to eliminate some types of structural features and to include others. Figure 10.11, which delineates the regions where different types of protons resonate in the NMR, graphically illustrates many of these rules.

Figure 10.11 is found on page 000.

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10 600

9 500

7 400

5 300

4 200

2 100

0 0

ppm ( ) Hz

Figure 10.21. The NMR spectrum for the first NMR spectrum analyzed in this section.

Consider the NMR spectrum in Figure 10.21. It has four signals, indicating that the molecule contains four types of protons: two singlets at 7.2 and 2.3 ppm, a multiplet at 2.7 ppm, and a doublet at 1.3 ppm. Use the above rules to tentatively identify the types of molecular features present in the molecule. The peak at 7.2 ppm indicates an aromatic ring (Rule 3). The signals at 2.7 and 2.3 ppm indicate that there are two carbons bonded to the aromatic ring (Rule 7). The signal at 1.3 ppm simply indicates some hydrocarbon section of the molecule (Rule 8). Next, determine the integration ratios for the number of hydrogens present. They are 4:1:3:6. Not having a molecular formula, you don't know for sure how many hydrogens there are. To begin with, use the total of the integrals as the number of hydrogens present. That number is 14. Because 14 is an even number, it might be that 14 is the number of hydrogens in the molecule. Now, look at the details of the signals. The peak at 7.2 ppm indicates an aromatic ring that does not contain any electron-donating or electron-withdrawing groups. Because the integral for this signal indicates 4 protons, the ring must have two substituents. In addition, the substitutions must be symmetrical or nearly symmetrical because the signal is a sharp singlet. A sharp singlet is typical of many para substituents and of some ortho substituents, as long as the two are similar. Usually, a pair of meta substituents has a more complex aromatic region than either an ortho or para substituted molecule.

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or

An example of the NMR of an ethyl group is in Figure 10.17, page 000.

The septet at 2.7 ppm and the doublet at 1.3 ppm with an integration ratio of 1:6 is typical of an isopropyl group. You should learn to recognize this pattern and the ethyl pattern, which is a quartet and a triplet. Both patterns are common in organic molecules. The signal position of 2.7 ppm is typical of a CH group on an aromatic ring (1.6 ppm for the position of a methine, CH, group + 1.3 ppm for the shielding constant of the aromatic ring). The doublet at 1.3 ppm is typical for a methyl group to an aromatic ring (0.9 ppm for the position of a methyl group + 0.3 ppm for the beta shielding constant of the aromatic ring). You can now add the following substituent.
CH(CH3)2

The remaining signal is a singlet at 2.3 ppm that integrates for 3 hydrogens. This signal indicates a methyl group attached to the ring (0.9 + 1.3 ppm). Thus, the structure is either ortho- or paraisopropylmethylbenzene. The effects of the substituents on the ring protons is more symmetrical for the para than for the ortho substitution pattern.
CH(CH3)2 CH(CH3)2

or
CH3 H3C

It is probably the para isomer, as the para isomer is more likely to have a singlet for the ring protons than the ortho isomer.
H H CH3 CH CH3 H3C H H

1.3 ppm

2.7 ppm

2.3 ppm

7.2 ppm

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Deciding between these two isomers based only on the NMR spectrum would be difficult. However, if you ran an IR spectrum of the compound, you could immediately tell that the NMR spectrum is of the para isomer. The ortho isomer has an IR absorption at 730 to 690 cm1, while the para isomer has an absorption at 830 to 780 cm1. Figure 10.22 shows another NMR spectrum for guided analysis. Because it has three signals, the molecule it represents contains three types of protons. The signal at 3.4 ppm indicates the presence of a carbon bearing either an oxygen or a halogen. The signals at 1.6 ppm and 0.9 ppm are for sp3 hydrocarbon sections of the molecule.

10 600

9 500

7 400

5 300

4 200

2 100

0 0

ppm ( ) Hz

Figure 10.22. The NMR spectrum for the second NMR spectrum analyzed in this section.

The integration ratios are 2:2:3. That adds up to seven, which is an odd number of hydrogens. Because the total is an odd number, the molecule must have either a substituent that does not appear in the NMR, an ether or halogen, or the actual number of hydrogens is a multiple of the integration values. As you continue with the analysis, work from both assumptions. The signal at 3.4 ppm, which integrates for two protons, must be a CH2 group attached to either a halogen or an oxygen. Because the predicted position for a chlorine (1.3 + 2.3 ppm) or an oxygen (1.3 + 2.4 ppm) are so close, include both as a possibility. If the substituent is an oxygen, the group is an ether because the spectrum does not show an OH proton signal. From this information, you know that the molecule is either an alkyl chloride (CH2Cl) or a symmetrical ether (CH2OCH2). Because the peak at 3.4 ppm is a triplet, it must also

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represent a proton group adjacent to two hydrogens, probably another CH2 group. The signal at 1.6 ppm, which is split into a sextet and integrates for 2 protons, appears to be a CH2 group adjacent to five protons. Because chlorine has a larger shielding constant (0.6 ppm) than does an OR group (0.3 ppm), the position of the signal is closer to that of a hydrogen to an ether (1.3 + 0.3 ppm) than that of a hydrogen to a chlorine (1.3 + 0.6 ppm). Thus, the molecule is more likely a dialkyl ether, but it needs some confirmation. Below are the fragments identified to this point. CH2CH2OCH2CH2 or CH2CH2Cl The final signal is a triplet at 0.9 ppm that integrates for three protons. In order to be consistent with the analysis of the sextet signal, this fragment must be a CH3 group adjacent to a CH2 group. Adding this to the fragments above, the spectrum is likely one of dipropyl ether, but may possibly be 1-chloropropane. There is not enough proof to know for sure. CH3CH2CH2OCH2CH2CH3 or CH3CH2CH2Cl The spectrum is of dipropyl ether. Running an infrared spectrum would immediately show a strong peak around 1050 cm1 for the CO bond of the ether. Exercise 10.7 Make structural generalizations about the types of protons in each of the spectra shown below. If possible, determine the actual structures that gave rise to the spectra. a)

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10 600

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0 0

ppm ( ) Hz

b)

+10 ppm

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c)

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Sample solution c) The complex pattern of peaks between 4.7 and 6.1 ppm is typical of the three signals of a terminal vinyl group. This is another pattern that you should, along with the ethyl and isopropyl groups, recognize instantly. The integral values from left to right are 1:1:1:1:1:3. The signal at 1.1 ppm is a methyl group adjacent to a single proton and, because the signal at 4.1 has five peaks, it is a CH group adjacent to four protons. The proton at 2.5 ppm is a single proton not magnetically coupled to the other protons in the molecule. Adjacent protons do not usually split a typical alcohol OH group. Thus, this molecule has the following fragments: CH2=CH, CHCH3, OH Exercise 10.8 The molecular formulas for the three compounds are: C4H8O2, C8H8O2, and C4H8O. What are the structures for the three compounds? Sample solution c) This molecular formula confirms the fragments proposed in Exercise 10.7 above. You can assemble these three fragments in only one way.

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OH
The molecule is 3-buten-2-ol.

SidebarMagnetic Resonance Imaging

Physicians have used NMR since the early 1980s to obtain images of tissues from living beings. This technique, known as magnetic resonance imaging (MRI), involves placing an individual in a magnetic field and irradiating that person with pulses of radio frequency. The radio frequency pulses excite the protons and as the protons relax, they emit a signal called a free-induction decay signal. A computer, using Fourier transform techniques, then processes this signal into an image. Figure 10.23 is an image of a normal human brain using MRI. This image is essentially a map of the density of protons contained in the water and lipid molecules in the brain.

Figure 10.23. Image of a normal human brain obtained by the technique of magnetic resonance imaging.

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The relaxation time is the time that an excited nucleus returns to its ground state.

Two important factors in the formation of the image are the presence of proton containing molecules and the mobility of the molecules. The most important factor is the presence of protons in the molecules in the head. Bones have few proton-containing substances and thus do not show up in the image. The instrument plots the various types of tissues using the relaxation times of the substances in these tissues. During relaxation the excited nucleus returns to a lower energy state. The relaxation times depend on the mobility of the molecules. Physicians use this plot to differentiate between healthy and diseased tissues. Relaxation occurs by several different processes. One is spinlattice relaxation. With spin-lattice relaxation the energy of one nucleus dissipates to nuclei in adjacent molecules. The time required for a nucleus to lose energy by spin-lattice relaxation is called T1. In another process for relaxation the excited nucleus transfers its energy to a single adjacent atom. Chemists call this process spin-spin relaxation. The time required for a nucleus to lose its energy in this manner is called T2. The amount of intermolecular contact is the main factor in determining the values of T1 and T2. For pure water the values of T1 and T2 are both about 3 seconds. For water in biochemical systems, the times are shorter ranging from .5 to 2 seconds. The more mobile the molecule, the less intermolecular contact there is between molecules, thus, the relaxation times become longer. In a biochemical system because water is mixed with a number of other components, individual water molecules are less mobile and thus have more efficient relaxation times. For larger molecules, the values of T1 and T2 are shorter, because they undergo relaxation more efficiently. With many molecules, and that includes water in biochemical systems, the values of T1 and T2 are different. A change in the environment also affects those values of T1 and T2. With tumors, lesions, or scar tissue the relaxation times of the proton containing molecules are different from the relaxation times in surrounding tissues. If, for example, the interval between radio frequency pulses is short compared to T1, the second pulse arrives before the nuclei have relaxed from the first pulse. Thus, there is no energy absorption and no signal is obtained from that tissue. Some regions have a large T1, whereas, others have a large T2. The computer assembling the image uses different timings and different orientations of the radio frequency pulses to obtain a detailed map of the different relaxation values. This imaging allows a physician to get a detailed picture of soft tissues without the damaging effects of x-rays or the need to inject contrastenhancing agents. Figure 10.24 shows an MRI image of the brain of a patient with <************>. <<<<<<<<<<<<Need Image>>>>>>>>>>>>>

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Figure 10.24. MRI image of a brain of a patient with <**********>.

Compare Figure 10.24 with Figure 10.23. You can see that Figure 10.24 has a region corresponding to the <*********>. The water molecules in this region have a shorter/longer relaxation time and thus appear darker/brighter than the surrounding healthy tissues.

10.10 Strategy for Solving Spectral Problems

Before you can use IR, NMR, and MS to accurately determine the structure of an unknown organic compound, you must work from a strategy, and you must understand the strengths and weaknesses of each type of spectroscopy. Until you gain an intuitive grasp of spectroscopy, simply scanning the three types of spectra looking for the obvious likely leads to failure. Table 10.6 summarizes the information provided by each spectroscopic technique. Use this table only as an approximate guide because the details of the information provided by each technique depend on the compound you are analyzing.
IR NMR MS Functional Groups E H S Alkyl Groups S E H Heteroatoms S S E Molecular Weight N N E Molecular Formula N S E Notes: E - Essential, H - Helpful, S - Sometimes, N - Never. Table 10.6. Utility of the various spectral types in determining molecular features.

Here are some suggestions for using IR, NMR, and MS spectra to determine the structure of an unknown organic compound. Take a sheet of paper, divide it into three columns and label the columns IR, NMR, and MS. In the appropriate column keep notes about the molecular features that you see in each spectrum. As you work, propose molecular structures and test them. Work carefully and you will successfully identify the compound. When considering the spectra, keep in mind the types of information available in each type of spectra. Refer to Table 10.6 if you need help. Use the following guidelines to assist your search for molecular features from each type of spectroscopy. IR Use the IR spectrum to help identify the functional groups present in the molecule. Then combine the IR spectrum with the MS to confirm the presence of any nitrogen-containing

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functional groups. If there is an OH group present, suspect that the molecular weight of the tentative molecular ion is low by 18 because of loss of water. NMR Use the NMR spectrum to confirm the structures of the alkyl groups and to suggest the locations of the functional groups, heteroatoms, alkenes, or aromatic rings. Do this by considering the effect of the particular group on the chemical shifts of nearby protons. MS Look for the molecular ion and determine its molecular weight. This is the molecular weight of the molecule you are identifying. Remember, however, that the molecular ion may not be visible. Also, when the molecular ion is small, the M+2 peak may be too small to be visible. If the molecular weight is odd, nitrogen is present. A particularly large M+2 peak indicates the presence of S, Cl, or Br. A peak at 127 or a mass loss of 127 usually indicates iodine. After you finish with this preliminary examination of the three types of spectra, decide on a tentative molecular formula and propose a few tentative structures. Then consider each structure, accounting for all its features in the spectra. Ask yourself the following questions. 1) Does the structure account for the major stretching frequencies of the IR? 2) Does it account for the chemical shift and any spin-spin splitting of each proton in the NMR? 3) Does the structure have the same molecular weight as that obtained by the MS? Figure 10.31 contains a set of spectra illustrating the above procedure. This set of spectra includes the IR, NMR, and MS of a single pure compound.
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Figure 10.31. IR, NMR, and MS of a single pure compound.

The IR spectrum in Figure 10.31 clearly shows an OH group at 3300 cm1. In addition, it shows some type of sp2 CH bonds with weak peaks in the 3100 to 3000 cm1 range. The peak at 1050 cm1 confirms that the alcohol is an aliphatic alcohol. The integration in the NMR is 5:2:1:2. The signal at 7.2 ppm in the NMR confirms the presence of sp2 CH bonds on an aromatic ring. Because this signal integrates for five protons, the ring is monosubstituted. The IR peaks at 740 and 690 cm1 confirm the monosubstitution. The MS indicates the molecular ion has a mass of 122 with a base peak at 91. This information, along with that gathered from the IR and NMR, makes it possible to deduce the molecular formula.

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122 Molecular weight 77 Phenyl group 17 OH group 28 Unaccounted mass Assuming that only carbon and hydrogen remain, a mass of 28 gives a formula of C2H4. Thus, the molecular formula is C6H5 + OH + C2H4 = C8H10O. Putting together all this information makes it possible to propose the following two structures. Both fit the data accumulated to date. Each molecule contains an alcohol and a monosubstituted aromatic ring with a two carbon chain.
OH OH

1-Phenylethanol

2-Phenylethanol

Going back to the spectra to confirm the proposed structures, the first molecule does not fit in with the integration of the NMR. The alkyl groups have a 2:2 ratio in the NMR, but 1-phenylethanol has a 1:3 ratio. The second molecule does fit. Therefore, the molecule is 2phenylethanol. Exercise 10.9 Below are IR, NMR, and MS spectra for two different compounds. Following the above example, make a list of the structural characteristics for each of the compounds that you find in the individual spectrum. Then combine this structural information and propose a compound that fits the data. Finally, verify that the structure you proposed accounts for the major features of all three spectra.

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Compound 1
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Compound 2
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Sample solution Aside from saturated alkyl groups, the IR of compound 2 shows little above 1500 cm1. The strong peak at 1100 cm1 suggests an ether. The positions of the peaks in the NMR indicate protons adjacent to an

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electronegative atom. These peaks are consistent with the presence of an ether group. The molecular weight of the molecule from the MS is 90. To calculate the molecular formula, subtract the oxygen (90 - 16) to get 74. Assuming the remaining portion of the molecule is carbons and hydrogens, this gives possible formulas of C5H14 or C6H2. Neither of these formulas is even close to the molecular formula of a alkane. The formula of C4H10 fits the formula of an alkane and the NMR integration. If compound 2 is an ether, the integration ratio of 2:3 suggests that the molecule is symmetrical and the actual ratio is 4:6. The weight of C4H10 is 58. Remaining is 74 - 58 = 16, the weight of another oxygen. Thus, the formula is C4H10O2. The following structure is the only four carbon symmetrical diether. CH3OCH2CH2OCH3

Key Ideas from Chapter 10

Hydrogen nuclei exist in two energy states when placed in a magnetic field. In the lower energy state, the magnetic moments of the nuclei align parallel to the external field. In the higher energy state, they align antiparallel to the external magnetic field. While aligned, the lower energy state nuclei absorb radiofrequency energy and go to the higher energy state. Chemists call this change resonance. The record of the exact energies required for resonance is a nuclear magnetic resonance spectrum. An NMR spectrum gives four types of information: 1) the number of sets of nonequivalent hydrogens, 2) the relative numbers of each type of hydrogen, 3) the chemical environment for each type of hydrogen, and 4) data about other nearby hydrogens through spin-spin splitting. Determining the structure of an unknown organic molecule using only one of the spectroscopic techniques is difficult; using a combination of IR, NMR, and MS with the proper strategy makes it relatively easy.

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