Determining Molecular Structure by Nuclear Magnetic Resonance of Hydrogen NUGENT F. CHAMBERLAIN Research and Development Division, Humble Oil & Refining Co., Baytown, rex. ,This paper presents a method for rapid and accurate determination of important features of the molecular structure of hydrocarbons and their derivatives, for either pure compounds or mixtures of compounds. This technique has been developed from a detailed study of the spectra of over 400 pure compounds obtained under standardized and reproducible conditions. The chemical shift information is summarized in a series of charts. This technique has saved many hours in petroleum research, in that a variety of organic functional groups under a wide variety of conditions can b e identified quickly and positively without precise calibration with the exact compounds being studied. It has been used to identify the starting compounds, reaction intermediates, and products in organic chemical research problems, and to characterize petroleum hydrocarbon mixtures. This technique should add substantially to the knowledge of the structure of complex organic compounds.
T
instrumentation and technique of nuclear magnetic resonance have been developed to the point where the NMR spectrometer has become a reliable and useful analytical tool. It is being applied rather extensively to a variety of problems in physical and organic chemistry, sometimes with dramatic results in terms of the speed and accuracy with which difficult problems can be solved. In the most favorable cases, the proposed structure of a relatively pure compound can be completely confirmed or rejected in 10 to 15 minutes. The basic principles of nuclear magnetic resonance spectrometry are discussed by Andrew (5) and Gutowsky (8) and reviewed by Reilly (34). Briefly, the high resolution S M R spectrometry of hydrogen provides information concerning the chemical nature, spatial position, and number of each type of hydrogen present in a molecule. HE
The absorption band locations (the chemical shifts) indicate the chemical nature of the hydrogens and provide some information concerning their spatial positions. The band multiplicities produced by
56
ANALYTICAL CHEMISTRY
spin-spin interaction provide additional information concerning the spatial positions of the hydrogens. The band intensities, under proper operating conditions, are directly proportional to the number of hydrogens contributing to the band (42). Xeyer, Saika, and Gutowsky (R?'), after a study of the K&IR spectra of over 100 compounds, concluded that high resolution KMR appeared promising in organic structural and qualitative analysis. Their summary chart of the chemical shifts of various hgdrogrn-containing functional groups is suitable for identifying broadly the chcrnically different types of hydrogen present in a molecule, and has led to development of techniques for characterizing petroleum fractions (61). Althrough this chart has been used widely in the determination of molecular structure, overlap of the chemical shift ranges of the various functional groups is so great that it is usually necessary to confirm proposed structures by comparing their spectra with the spectra of a number of pure compounds having structural features similar to those of the unidentified compound. If this overlap could be reduced appreciably, structural determinations could be greatly speeded. This calls for a marked improvement of the correlation of chemical shift n-ith hydrogen type. Information obtained with the better instrumentation, techniques, and theory now available indicated that the possibility of improving this correlation justified a detailed study. During this study, the spectra of over 400 compounds were produced under standardized and reproducible conditions for the specific purpose of achieving the best correlation of chemical shift with hydrogen type under conditions encountered in normal analytical work. The conclusions and correlations presented here are based on a systematic study of these spectra. A dramatic improvement in the chemical shift correlations and in the speed of organic structural determinations has been achieved. This paper presents this analytical method in detail, so that e v m those new to the field can use it, and those contemplating the use of N h l R can evaluate its advantages.
ADVANTAGES AND DISADVANTAGES
High resolution nuclear magnetic resonance spectrometry has the follon ing advantages and disadvantages in petroleum and organic chemical analysis.
Advantages. It is generally faster than other spectrometric techniques because of simpler sample preparation, shorter running time, or simpler interpretation requirements. It supplies unique information in many cases, or complements information supplied by other analytical methods. Intensity calibration is not necessary. Chemical shift calibration can be entirely indirect. Both are of great importance in the study of compounds for which no direct calibration samdes are available. It is nondestructive to the sample. The s a m d e can even be sealed in elass tubes, &der vacuum or inert gas if desired. Only a small sample is required, varying from 0.3 to 0.01 cc., depending on the nature of the sample and the information needed. It is relatively insensitive to sample impurities. This is an advantage when the major component of a mixture is being studied, but a serious disadvantage when minor constituents are to be studied. Disadvantages. High resolution equipment is complex and expensive ($35,000 or more), as is its maintenance. A highly skilled operator and maintenance personnel are required. The sample must be a liquid of low viscosity. Gaseous and solid samples must be liquefied or dissolved in suitable solvents and viscous liquids must be diluted. Quantitative accuracy is not as good as desired, but is being improved. The method is not useful for trace analysis. PROCEDURE FOR PRODUCING SPECTRA
Most of the spectra used in this study were obtained on a prototype of the Varian V-4300 high resolution N M R spectrometer (Varian Associates, Palo Alto, Calif.), operating a t a frequency of 30 hfc. and a field strength of 7047 gauss. The magnet was equipped with the V-K3506 superstabilizer system and associated slo~vsweep unit to improve stability and resolution. Samples werc
contained in h i m . outside diameter glass tubes which nere spun a t a rate of about 900 r.p.m. to average out the horizontal field gradients. Spectra nere recorded with a Sanborn Model 151 galvanometer type recorder (Sanborn Co.). Slveep rate of the magnetic field and the horizontal chart scale were deterniined frequently (about every 30 minutes or less, as conditions required) by nieasuriiig the displacenient between the peaks produced by pure toluene. The value (40) used for this displacement was 48.4 parts per 10,000,000 (34.1 niilligauss a t 30 Mc.). Nore recent measurements of this displacement by tlie sideband technique indicate this value is 49.0 parts per 10,000,000 (p./lO M.), but the earlier value has been retained to be consistent. For record spectra the sweep was always from low to high field. Because high resolution spectra can be obtained only on liquid samples of low viscosity, and present equipment does not permit running samples a t temperatures much removed from room temperature. solvents were necessary n i t h ninny samples. Solvents were chosen to produce minimum distortion of or interference with the sample spectrum. The sample frequently had to be observed in several different solvents to determine the true and complete sample spectrum. All peak displacements were measured with respert to the peak produced by a suitable internal reference standard dissolved in the sample, and calculated as displacements from the peak produced by benzene. Measurements were made directly from the recorded spectrum, To reduce the error due to magnetic field instability remaining after superstabilization. it n-as necessary to use a sweep rate of 1.2 p./10 Ill. per second. K h e n necessary to achieve higher resolution, additional scans were made at slower sv-eep rates. Samples were not degassed. Repetition of some of the work at a frequency of 40 l I c . , using the necessary T'arian equipment. has confirmed the validity of the chemical shift data at this frequency. INTERNAL vs. EXTERNAL STANDARDS
With w r y fciv euceptions, present X l I R spectrometers are not sufficiently stable to permit long-term calibration on the magnetic field. Therefore, with each sample a standard has to be employed which establishes the reference point for determining tlie peak displacements. For some types of work a reference standard is desirable even when long-term stability of the magnetic field has been achieved. The reference material may be external to the sample, or niised n i t h the sample as a n internal qtandard. The choice of external or internal standardization depends on the type of information desired and the objective of the work. A knonledge of the characteristics of
each type of standard is a prerequisite to making this choice. External Standards. An external standard is essentially a means for calibrating t h e magnetic field external t o t h e sample cell. It establishes a fixed point in field strength n i t h o u t regard to t h e nature of t h e sample involved. consequently, a n y factors in t h e sample itself nhich affect t h e magnetic field a t a n observed nucleus lvill change the position of its resonance with respect to a n external standard. This is desirable when studying the nature and extent of all the influences which can produce shifts in the SAIR resonance bands. The factors which affect the magnetic fields within the sample cell are discussed by Reilly (34). Their relative importance is indicated by the magnitudes of the shifts they produce in the compounds studied :
Shifts Due to Variations in Llolecular structure hIagnetic susceptibilitSolvent (nature and conen.)'
Magnitude, p./lON. 0 to 90"
References (8,27)
0 to 6*
(fl-14)
0 to O d
[ I 3(cf. 2,11,
I?, 18,44, 40 11 Kith some OH shifts ranging to 140 p./10 31. Referred to benzene. e Includes changes in molecular n-eight in some cases. After correction for magnetic susceptibility.
For the chemical shift to be really useful for structure determinations, the shift of a chemically distinct hydrogen type must be reproducible to about 4 pJ10 11.or less under all conditions encountered in normal analytical TT-ork. Shifts produced by combined solvent and susceptibility effects must be reduced below this level. \Then external standardization is used, it Tvill be necessary to measure all the extraneous factors and correct for the total shift they produce for each sample. Alternatively, these effects can be eliminated by extrapolating the chemical shift data to infinite dilution of the sample in a magnetically isotropic solvent such as carbon tetrachloride or tetraniethylsilane. Internal Standards. T o study only t h e effects of molecular structure on N J I R spectra, it would be faster and more convenient t o employ a standardization scheme which eliminates t h e need for t h e corrections describes in t h e preceding section. A properly chosen internal standard provides a means of calibrating the magnetic field a t the sample molecule, so that, essentially, only the effects of molecular
structure on chemical shift are observed. Because sample and standard are molecularly dispersed, the bulk magnetic susceptibility of the resulting solution affects the field about both types of molecules in the same way and produces the same shift in the spectra of both. K h e n factors other than changes in bulk magnetic susceptibility do not interfere, the relative shift between sample and standard peaks remains constant. Then the positions of the sample peaks relative to the standard, nhich is assigned a fixed value, remain constant regardless of the magnetic susceptibility of the resulting solution. This is n ell demonstrated by Bothner-By and Glick (12). Thus the internal standard eliminates the shifts due to magnetic susceptibility. The effect of concpntration and of solvent can be reduced to a satisfactorily low value if internal standards can be found having resonance peaks 15 hich shift in tlie same direction and a t essentially the same rate as the resonance peaks of the sample being studied. Simple aliphatic molecules can be used as reliable internal standards for one another ( I $ ) , and cyclohexane and some paraffins are satisfactory (as defined in this mork) internal standards for some aromatics (13. 45). The question remaining was n hether satisfactory internal standards for n ide classes of other compounds could be found so that only a few standards viould be needed. Tiers has shown that tetramethylsilane is a very good internal standard for use with a wide variety of compounds observed in low concentration in carbon tetrachloride (36). It has been found in this laboratory that a relatively small number of compounds can be used successfully as internal standards for a wide variety of compounds observed a t all concentrations in any one of several convenient solvents. although some precision must be sacrificed. The compounds used as solvents and as internal standards in this study are listed in Table I. The chemical shifts of the standards were determined, when possible, by direct internal standardization with benzene. One disadvantage of internal standards is that they contaminate the sample. When such contamination cannot be tolerated, it is necessary to use external standardization and make the necessary corrections. Procedure for Standardization. Liquid samples were a l ~ v a y sobserved without internal standards first, and t h e spectra so obtained n-ere used t o determine t h e relative displacements of t h e resonance peaks. Then t h e sample was observed again after addition of about 10 to 50 mole % ( 5 t o 10 volume %) of the standard compound VOL. 31, NO. 1, JANUARY 1959
57
to determine the displacement of the resonance peaks from the standard and thence from benzene. Time mas saved by controlling the concentration of the standard only roughly. For rapid analytical work this is desirable. Relative shifting or distortion of the sample peaks was observed to obtain information on hydrogen-bonded hydrogens or on sample-standard interactions which might be useful or detrimental. When detrimental interactions were observed, the sample was rerun u-ith a different standard compound. The effects of solvents, \Then used, were revealed by observing the sample in several different solvents. Hydro-
Table I.
gen-containing solvents yere usually used as the standards also. If the solvent was a n unreliable standard under the circumstances, an additional standard compound was added. Time was saved by not measuring or controlling solvent concentration. Development of the basic data in this way makes them directly applicable to compounds of varying solubility and to mixtures of varying composition: this is time-saving and idens the range of applicability of the technique. CHEMICAL SHIFT
The feature of an YAIR spectrum which gives the most information about
Internal Standards and Solvents for NMR Spectrometry
Positions of Peaks, p./lO M. Compound Abbrev. Primary Use from Benzene Acetone .4 Solvent standard for oxygenated com53.1 pounds Benzene B Standard for nonaromatic compounds. 0.0 Tends to produce marked relative shifting of peaks in aromatic and certain other types of compounds Carbon disulfide Preferred solvents for all applicable situ... Carbon tetrachloride CC1, ations, because no proton spectra are Droduced Chloroform Cm Sofvent. Not a reliable standard, pos1.4 sibly because of its tendency to form hydrogen bonds ( 2 5 ) Cyclohexane C Preferred standard for aromatic com55.8 pounds and other compounds where applicable Dimethyl formamide DMF Solvent standard for many types of compounds studied. Main disadvantages are interference caused by aldehyde peak to spectra of aromatic compounds and formation of a false peak in spectra of certain quinoids, condensed aromatics, and alcohols. The best general solvent found llid-point between methyl peaks 45.1 hldehyde peak -5.8 Dimethyl sulfoxide D l I S Solvent standard for oxvgenated com47.4 .pounds 1,4-D Solvent standard for oxvaenated com1,4-Dioxane 36.6 pounds HMDS Standard for all types of compounds? Hexamethyl 70.7 disiloxane Kot yet widely tested HMPA Has solvent properties approaching Hexamethyl phosphoramide those of dimethyl formamide, but does not produce the undesirable aldehyde peak. Solvent standard Midpoint between methyl peaks 47.2 Methanol RIeOH Solvent standard for oxygenated or nitrogen compounds 39.2 Methyl peak OH peak not useful as internal standard Pyridine P Solvent for certain compounds not soluble in other solvents. Unreliable standard Peak 1 -17.3 Peak 2 -3.4 Toluene To1 a. Standard for nonaromatic compounds Ring peak 0.4 48.8 llrthvl neak b. Standarh for calibrating sweep Displacement between peaks 48.4 a Water W Solvent for polycarboxylic acids and salts. S o t suitable for internal standard Peaks produced by hydroxyl groups shift markedly with changes in solvent and concentration and are unreliable for use as standards. Deuterated forms of the solvents, especially CDCll and D20, are useful when solvent peaks interfere seriously with sample spectrum. " I
(I
58
ANALYTICAL CHEMISTRY
the chemical nature of the hydrogens in the sample is the chemical shift. Theoretical mathematical expressions for chemical shifts which have been developed to date (26, SO, 31, 3.9, %') are unsuitable, because of complexity and uncertainty, for use in general analytical nork. The fastest and most accurate way to determine chemical shifts for general analytical nork is to measure them for typical functional groups. This involves considerable work, but once the information is correlated, identification of the functional groups present in a sample is speeded. Measurement. The chemical shift of a given functional group is t h e displacement in terms of frequency, magnetic field, or dimensionless units from the reference position to t h e position which would be occupied by the resonance peak of that group if it produced only one sharp peak. Because of spin-spin coupling among atoms, hindered internal motion in some molecules. relaxation broadening, and peak enhancement effects. the resonance band produced by a group of chemically equivalent hydrogens may, under different circumstances, vary from single or multiple sharp peaks to single or multiple broad peaks, and the bands may be a>-nimetrical or asymmetrical. The position from \\-hich the chemical shift should be measured in some of the complex bands is not obvious, and mathematical selection of the precise chemical shift is often difEcult and involwd (4). Therefore, an approximation of the chemical shift has been used in all cases. The spectra of Figures 1 and 2 were not obtained a t the iiiasimuni resolution of which the instrumcnt v a s capable. The second-order splitting which becomes visible a t iiiasinium resolution is neither necessary nor dcsirable for chemical shift nieasurtments. I n general, the band position is t8aktw as the center of arca of the band of peaks produced by a group of equivaleiit hydrogens. I n Pigurc, 1, A and B, all the bands are ncll separated from each other, so that t'he band positions are taken as the geometric centrrs of the essentially syminrtrical hands. In B this may not be obi-ious for the a-CH group, which ronsists of seven peaks, because the last two peaks on the high field side are difficult to discern. Figure 1, C, presents the problem of selecting the band position for the /3-CH2 and y C H , peak groups which are not well separated. The peaks nearest each other in the t n o bands are enhanced so that the bands are no longer symmetrical and the center of area is no longer the geometric center of the bands. For convenience the band positions were selected as the center of the -y-CH3 triplet and the peak just to the high field side of the
R
-CH,
A. ETHYL 4LCOHOL HC-
*
9 'SOPROPYL ALCOHOL
hO
?
-
H~C-CC-CH~ I 0
)\
/I
H
i1:
Y
HOC
c n-PROPYL
ALCOHOL
-CLo
:
:
-.&.-.$-,
>
i
: :
: >
: : :
: :
I
: :
I
:- : :
8UCREASlWG MAGNETIC FIELD ( t i 0 1 ----*
Figure 1.
cc,nti>r of the O-CH, sestet (the cnd peaks of this sextet do not show). The, umctsrtainty is of the order of 1 to 2 p. '10 11. a t the worst. In the high field end of Figure 2, A , the n l k ~1 groups have produced peaks n hicli are w r y close together, and very poorly Irsolved. and for nhich the wlection of band pcsitions is a t best a gu('s5.. In such cases the highest field pcnlL has bccn designated as thc posi-
Resonance band positions for lower aliphatic alcohols
tion of the band produced by the terminal methyl group, n i t h the position of the CH2 bands designated as indicated. I n Figure 2 , B , the problem of a n asymmetrical doublet produced by the y-methyl group ariseq. In this case. the band position has been chosen as two thirds of the way from the smaller peak tonard the larger. The band position for the 6-CH group has been chosen a t what appears to be
about the geonirtrical center of the band. This band is qo broad t h a t even though its high field peak merges n i t h the doublet produced by the methyls, the shape of the band does not seem t o have been changed unduly. Figure 2 , C, illustrates overlapping peaks. The band positions h a w been chosen as follon s: for -y-CH3,center of the triplet it produces; for P-CH,, center of doublet i t produces; for P-CH?, the
c.
8
I
Figure 2.
ISOBUTYL
C. S E C O N D A R Y
ALCOHOL
BUTIL
ALCOHOL
(*
TR8CI
XCLJ
Resonance band positions for butanols VOL. 31,
NO. 1, JANUARY 1959
59
position of the fourth peak of the quintet it produces (asymmetrical band) ; for OH and a-CH, centers of their bands. Figure 2, D, consists of only two sharp well-separated peaks and the band position is a t the center of each peak. For more complicated spectral groups the band positions were chosen on the basis of the work of Bernstein et nl. (9) and Pople et al. (52). Causes. Chemical shifts may be attributed to secondary magnetic fields set up by several types of electronic currents induced into the molecule by the applied magnetic field (26, 31, 36’). These secondary fields, and therefore the chemical shifts, are directly proportional to the strength of the applied field. Local diamagnetic currents induced in each atom produced a field proportional to the electron density of the atom. This field opposes the applied magnetic field, causing the nucleus to resonate a t a higher applied field and increasing the chemical shift. Thus, other factors being equal, the chemical shift of a hydrogen-containing group should increase linearly with decreasing electron-withdrawing power (electronegativity) of adjacent groups. This is true for simple aliphatic molecules ( 2 , 7 , 19). Paramagnetic currents may be set up corresponding to the mixing of ground and excited electronic states by the applied magnetic firld. The magnetic field set up by the paramagnetic currents reinforces the applied field and decreases the chemical shift. I n aromatic rings and possibly in some other structures there are intpratomic currents (pi electrons) flowing in closed circuit., around a molecular path. The aromatic ring may thus be considered as a one-turn closed conductor in which current is induced by a n applied magnetic field. The field produced by this current opposes the applied field in the vicinity of the faces of the ring and reinforces i t in the vicinity of the edges of the ring. The resonances of atoms and groups attached to the ring are shifted to lower applied field positions, but the resonances of atoms or groups held over the faces of the ring (by steric hindrance or molecular association) are shifted to higher applied field positions. Pople ( S I ) states that “for most nuclei, the magnitude of the chemical shift of a particular nucleus is determined principally by the local circulation on its own atom. Protons are exceptions, however, in that the total electron density on a hydrogen atom is relatively small, so that circulation in other parts of the molecule will be more significant.” This susceptibility of the hydrogen resonance t o the effects of nearby groups provides considerable useful information concerning such 60
a
ANALYTICAL CHEMISTRY
groups, even when they do not contain hydrogen. The effect drops off rapidly, because a t distances greater than one bond length i t is a function of l j r 3 , where r is the distance betneen group centers. Allred and Rochow ( 2 ) found that the effect of strong electronegative groups in shifting the resonances of hydrogencontaining groups to lower applied field positions extends to a significant degree to groups beta to the electronegative group. This study confirms this and further indicates a noticeable but negligible effect on groups as far removed as gamma to the strongest electronegative groups.
Thus, for the aliphatic alcohols, the hydrogens on the carbon to m-hich the OH is attached are labeled a-alcoholic hydrogens and those on the carbon atom beta to the alcohol group are the @-alcoholic hydrogens. These are recorded in the charts simply as alpha, beta, gamma, etc., n i t h the reference group named separately for each conipound type. The reference group is usually the strongest electronegative group in the molecule or is an aromatic ring. I n general, when tn-o strongly electronegative groups lie close to a third group of weaker electronegativity, the resonance of the weaker group is shifted to a greater extent than nould be caused by either of the other groups singly. This type of double-group shifting is indicated by the terminology az,a@, p2, etc. The squared term is used when a group of interest is located a t the same distance from t n o similar stronger electronegative groups (similar groups are those producing equivalent chemical shifts). Vhen the group of interest is alpha to one stronger elec-
CHEMICAL SHIFT CHARTS
Designation of Functional Groups. T o show t h e influence of key groups on chemical shifts, a reference group has been chosen for each compound type and other groups in t h e compound have been referred, by spatial position. to this reference group. The designation scheme is shown in Figure 3.
Linear
I
Chain Hz Hz Hz
A r o m a t i c Ring
1 Acid i
- CI C 1 - C-CHn I
O H- [
I
%
E l m I1
IAldehydic H P H - C
CH3
-
I I H
H
CH3 I
-C
C
I
El
- CH3
CHa
Ring R e f .
4 I ’ H
H
(Refla
-?-
”y 1?!!
E I H Chain
0
H
glRefl
Iftef.l@rnpJq Branched
c
& H onI Rin
E!
pJpJ
Note The same designations used for aliphatics ore olso used f o r alicyclics and cyclics Multiple H
?
Reference
Groups H
H
?
c - c - c Az
I
Hz
HlzJW
- C - c - c I
Hz
I
Hz
?
4 Refer en c e G r o upsl
1
Hz
mWI
T h e designation gr, g8, a s , and Y 2 6 although strictly applicable, a r e not used b e c a u s e the e f f e c t of t h e r e f e r e n c e group on t h e chemical group. s h i f t is negligible a t distances greater than t h e
Ole fins
Non-Terminal H
Figure 3.
G r o u p designations used in chemical shift charts
-70
-60
[ I I I I
-50
I
I I I I
I
-40 I I I 1
- 30
1 I I I I
I/
- 20 I I I
I
0
-10
I I I I
I
I I I 1
20
10
1-rTn-p
I I
I
30
50
40
I
I I I I ] 1 I 1 1 1 1 1 1 I
60 I I I I
I
1 1
1 ' 701
PARAFFINS AND OLEFINS PARAFFINS
I
-CH3 -CHp- i a t o m e t h y l ) -CHZ-(o+ to m e t h y l )
Reference:Group: -CH3
Short o r highiy b r a n c h e d chains-
CYCLOPARAFFINS (NAPHTHENES)
R e l a t i v e positions l o r e q u a t o r i a l o n d polar methyls 7
'A
-CH3
R e f e r e n c e : Ring.
a B+ 18
-CH2-
{2
H ON RING
::::
I
m
OLEFINS Reference: >C=C=
C o n j dtolef.-
Ie n e s
A-
TERMINAL OLEFINIC H
0
-CH:
A
C o n j . diolef
--
-Mono.olefins
I -A -Mona.oIafins
NON-TERMINAL CYCLIC O L E F I N S R e f e r e n c e : C:
-CH3
= C:
( a to
ring)
R e l o t t v e positions f o r e q u a t o r i a l and p o l a r m e t h y l s 2
C6 RING
RING A L K Y L H
C5 RING RING OLEFINIC H
{
,
MONO-OLEFIN RING 5
-70
56 5 8 6 -No
Imm
- S h i e l d e d
-
e p
aP-a 4 I I I
a2 I
o f
c a r b o n s in r i n g by M e g r o u p on o t h e r o l e f i n i c c a r b o n
6t
I I l I / I I l I I I l I I I I I I I I I I I I I I I I I I I I I I I I I I I I l 1 1 1 1 1 1 1 1 1 1 1 1 l 1 1 1 I I I I I I I l I I I I ~ - 60 - 50 - 40 - 30 -20 -10 0 IO 20 30 40 50 60 70
PARTS PER 10 MILLION FROM BENZENE
Figure 4. Hydrogen magnetic resonance chemical shifts
tronegative group and beta to a similar one, the term cup is used to describe its position. Because electronegative groups farther removed than beta from a given group have negligible influence on its chemical shift, double terms greater than cup are not used, unless the term is squared. For instance, the tcrm a y is not used, but the term y? is used in the charts. ay is recorded simply 3 s a , and P+y is recorded simply as p. For polysubstituted aromatic ring compounds it is often necessary to use tivo reference groups, one of the substituents and the ring, to show the locations of other functional groups. The strongest electronegative substituent is normally chosen as the primary refvrence group, and it is to this group that the simple alpha, beta, gamma, or 0. m, p refer. K h e n necessary to use the ring as a n additional reference point, the notations alpha to the ring, beta to ring, or ring reference are used. Description. T h e chemical shift information derived from this study is presented in Figures 4 t o 13. T o show distinctly as many useful characteristics as possible, a separate chart for each major compound t y p e is presented and these are further sub-
divided according t o type of suhstituent, size and number of rings, etc. Within each subsection the hydrogencontaining functional groups are listed separately, to shon the effect on the cheniical shift of the spatial position of each group n i t h rclspect to the reference group. The chart scales show the chemical shifts in parts per 10,000.000 of displacement from benzene. This is defined as chemical shift = 10'(H, Hb) 'Hb, nhere H , is the resonance position of thc sample and H , is the resonaiice position of benzene. Because ( H , - Hb) X4 a t 40 Mc., and XG at GO N c . ) . I n all cases, an increase of the scale numbers in the positil'e direction represents a n increase in the applied magnetic field.
If the ranges of cheniical shifts of two groups overlap, the total range of both groups may be indicated by a single bar on the chart n i t h small vertical lines to indicate the average locations of the individual sh.ifts. Khere practical, the actual amount of overlap is shown. Although the average accuracy found for the chemical shifts is of the order of + l p.,'10 AI.. the precision is better than this. Therclfore, for a series of compounds in n.hic*h the internal standard has a high degree of reliability. relative shifts of less than 1 p.,/lO 11.are indicaated with accuracy. For t'his reason sci-era1 chimical shift differences of less than 1 p.,,'10 11. are rccorded on the charts. Reliability. The number of compounds from n-hich d a t a w r e dcrived for each section of the charts is shown in Table 11. If a compound rightfully falls into two different classifications, it is counted in both. The charts were prepared by plotting t h e chemical shifts of every tlistinguishably different type of hydrogen /in every compound and then drawing bars t o include t,hc extreme limits of each group, as s h o n x in Figures 14 and 15. VOL. 31, NO. 1 , JANUARY 1959
61
Table 11.
Types and Numbers of Cornpounds Studied in Preparing Chemical Shift Charts
Compound Type
s o . of Compounds
Hydrocarbons Paraffins Cycloparaffins
Olrfins Polvole fins
Aromatics, 1 ring
Sormal Branched Cyclopentanes Cyclohexanes Condensed cycloparaffins Aliphatic CJ-clopentenes Crclohesenes Bicyclo (2,2,1) Ci Aliphatic Cyclo Cj Cyclo C6 Cvclo Cs Bicyclo (2,2,1) C7 Tricyclo C8 Methylbenzenes and benzene Other alkyl benzenes
Aromatics, multiring nncondensed Aromatics, 2-ring condensed 3 +-ring ring hromatic Uncondensed naphthenes Condensed ilromatic olefins
6 6 16
18
Monocarboxylic Dicarboxylic Monoalcohols Polyols
Alcohols
Aldehydes Esters (alcohol Of aliphatic acids moiety) Of alicyclic acids Of aromatic acids Esters (acid Of aliphatic moiety) alcohols Of alicvclic alcohols Of aromatic alcohols Ethers Ketones (nonaromatic)
Compoiind Type Alcohols Aldehrdes Esters (alcohol moiety) Esters (acid moietr)
4 16
3 12 3
-
1 1
Esters of aromaticsnbstituted aliphatic acids Ethers Ketones
1 1 1 1% 13
-
Phenols
-
Chlorine compounds
Bromine compounds Iodine compoiinds
Amines
5
Amides
k
Other
Monocarboxylic Dicarboxylic Alcohols Monoalcohols Esters (alcohol Of aliphatic acids moiety) (acid Of aliphatic moiety: alcohols Ketones (non- Monoketones aromatic) Diketones Crclic ethers 3-membered ring 5-membered ring 6-membered ring Furans Cyclic ester
1
rlromaticaliphn tic Aromaticalicvclic Aromaticaromatic Benzene mono-
Chloroalkanes Chlorocvcloalkanw Chloroal kvl aromatics Chloro olefins Bromonlkanes Bromoalkrl aromatics Iodoalkanes
-4liphatic Cyclic Aromatic monoamines Aromatic diamines Aliphatic Aromatic Pyridine Nitrobenzene
2
Siloxanw
1
2 6
3 6
3
2
3 1
Thioalkanes
-4romaticsubstituted aliphatic acids
62
ANALYTICAL CHEMISTRY
1
2
8 3
5 3
3 4 2 2
1
2 2 1
3 6
1 1 1
11 8 2
3
Thiocycloalkanes Thiols Aromatic sulfides Thiophenes Rnlfoxides
LTonothio Dithio
2 2 2
AliDhatic Aromatic
4 2 1
Aliphatic Aromatic
Bicyclo (2,2,1) C? compounds
XIonocarboxvlic Polycarboxylic
6 8
Sulfur Compounds
7 1
Aliphatic
Oxygenated Aromatics A4cids
13
Silicon Compounds
Oxygenated hlicyclics Acids
12
Sitrogen Cornpounds
1
-
5
13
Halogen Compounds
i
6 5 12 5 4 4 2 12 4
Of diphatsicacids Of aromatic acids Of aliuhatic alcohols Of aromatic alcohols
5 2
2
6
1
Monoalcohols
Benzene polyols
Quinones
5 4
Compounds
01s
i
Oxygenated Aliphatics Acids
s o . of
Olefins Diolefin hlcohol Esters Ketone
4
1 1
The most precise data obtained were from the alkyl benzenes. All but three were liquids which could be observed without solvent, most were of extremely high purity, all produced relatively sharp resonance peaks which made possible the highest precision in the chemical shift measurements, and cyclohexane proved to be an accurate and reliahle standard for all. Consequently. Figure 13 presents the best data which could be obbained by this technique. Ring hydrogrn and methyl hj-drogen shifts are precise to less than 1 p,'10 SI., so that the effects of methyl group shielding can be clearly defined. (Precision here refers to t h r repeatability of the chemical shift value for corresponding hydrogens in different compounds and different samples). The grcatest spread of Yalues, 4.5 p.,'10 AI., was obtained for the CH group in isopropylbcnzenes, but most of this spread (3.5 11. '10 AI.) \vas caused by one lon- value out of four. The low value n-as measured for the only one of these four compounds dissolved in a solwnt. ThuP the chemical shifts obtained for the alkyl bpnzenes are adequat'e for analytical work-that is, the unexplained spread of values is! n-ith only one exception, Ivithin the 4 p/10 AI. limit that espuience has elion-n to be desirahle. Certain samples, the most troublesome of vhich are the aromatic acids. are difficult to dissolve and there can be little or no control over s o l ~ e n type t or concentration. r o t only are these acids difficult to dissolve in acceptable solvents, but the fact that they are aromatic tends to make the solvent effects even more serious than they might he for nonaromatic conipounds. Figure 15, then, presents the least precise data obtained in this study. Because of space limitations, the data for only the monocarboxylic acids are shon-n. but the data for mono- and poljmrboxylic acids and esters are summarized in the chart section. In this case, the unexplained spread of values. excluding acid hydrogen shifts, ranges f r m i 1.5 p . j l 0 SI.. which is well within the desired limit, to 8.5 p./lO SI., which is over twice as great as desired. Furthermore, there is considerable overlap in most of the adjacmt chart regions. Consequently, these data are not so useful as the data for the alkyl benzenes, but' they h a l e been of apprrciable T.nlue in analytical n-ork. The magnitude of the chemical shift variations introduced by t'he use of different solvents is indicated in Table 111, u-hich presents the chemical shift' data for the compounds studied in more than one solvent. The range, rather than the standard deviation, is used as the measure of scatter of the data because the scatter is not random. It
-70 ~
- 50
-60 I
I
I
I
~
l
l
- 30
-40 l
l
~
l
l
l
l
-10
20
~
l
l
l
l
~
l
l
0 l
'
~
l
l
l
'
to ~ l
20 l
'
l
30 ~
l
T
50
40
T
l
60
AROMATICS A L K Y L BENZENES Reference
-6
-CH3
Aromatic Ring
No of methyl groups 3n r i n g
=
3 4
M U L T I RI NG UN CON DENS E D AROM A T I C s Reference
B v+ I t
Q
-CH:
m 62
012
r"
-CHz-
a
- CH3
Aromatic Ring
m
a2
-CHP-
-CH:
H ON RING
ab
I
I
a3
I
I
CONDENSED AROMATIC N A P H T H E N E S Reference
Aromatic Ring
a2aB
-CHz- IN NAPHTHENE BRIDGE 'Ondenled
H ON AROM RlNG
Arom
+ai
I
2
a
I
I
-
H ON AROM. RING
CONDENSED RING AROMATICS Reference: Aromatic Ring
H ON AROM. RING
AROMATIC O L E F I N S R e f e r e n c e . C:
= :C
1, -70
{
TERMINA L NON-TERMINAL H ON AROM. RING
OLEFINIC H
E
I
Single A r o m Ring
UNCONDENSED AROMATIC N A P H T H E N E S R e f e r e n c e : Aromatic Ring
Vrb+
III
No of a d p c e n l methyl groups
H ON RING
70
II l l l II ~ I I I I I1 1I 1 I 1 ~1 ' l 1 l 1 i
~ 1 I1
a E+
-CHz- IN NAPHTHENE RING
I
I
I
a
-CH3 -CH3
F o r t h e r l f r o m ring Closest to ring-
I
I
1I
-CHz-
4" i a f I '
I a a
?6 lo ring t o ring
Position w i t h r e s p e c t t o orom r i n g
I I I I l I I I l l l l l t l l l l I I I I I I I I I I I I I I I l I I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 - 60 50 -40 - 30 -20 -10 0 10 20 30 40 50 60 70
-
PARTS PER 10 MILLION FROM BENZENE
Figure 5.
is encouraging t h a t the range values vary only from 0.1 to 3.1 p./lO lI., averaging 0.9 p.AO SI., because all these values are vel1 within the desired precision. Gnexplained variations in chemical shift data presented in the remaining sections of the charts varj between the t n o extremes just illustrated. Most of these variations are small enough to permit the identification of the functional groups present in the samples encountered in everyday analytical nork. Some of the variations can probably be explained either in terms of structure variations or reduced in magnitude as instrumentation and technique? improve. The data presented so far shol\- that a given hydrogen type can be identified reasonably well from its chemical shift, provided the investigation is limited to the narron range of compounds included in a single shift chart section. For generally useful work, hoivever, the hydrogen type must be identifiable under all conditions and in all compound types normally encountered. The reliability n ith which comparable methyl groups may be identified in all
Hydrogen magnetic resonance chemical shifts
situations studied is indicated in Figure 16. Figure 16, A , shows that methyls alpha to single ring aromatics and not influenced by other functional groups have a chemical shift ~ l u of e 50 =t 2 p. '10 AI., while methyls alpha to multiring aromatics have a shift of 47 i. 1 p. '10 11. These narrow ranges of chemical shifts are characteristic of niethyl groups alpha to aromatic rings, and not influenced by other structural features, in all types of compounds and under all conditions studied. Likenise, a chemical shift of 57.5 =t 1.5 p.,'lO SI. is characteristic of methyls beta to aromatic rings and not influenced by other functional groups. Methyl groups gamma or farther from a strong electronegative or aromatic group or beta or farther from an olefin group, ar? influenced to a negligible extent by the reference functional group. Such methyls should be comparable to the methyls in paraffin chains, and Figure 16, A and B , shows this to be true under a11 conditions studied. The characteristic shift of paraffinic methyl groups is 62.5 i 2.5 p./10 11. To obtain maximum flexibility in predicting chemical shifts for new or un-
usual compounds it is desirable that the measured shifts of hydrogen-containing groups alpha to different strong electronegative groups be accurate enough to permit estimation of the relative shifts between them. Two studies of this point indicate that acceptable accuracy has been achieved. A study of the entire group of aliphatic alcohols and ethers indicated that the chemical shifts of the methylene hydrogens in -CH2-0and -CH2-OH groups overlapped so much that it \\a3 not practical to show them beparately. Yet a study of comparable alcohols and ethers (EtOH us. E t O E t , PrOH LIS. PrOPr, etc.) indicated there should be a difference in shift of approximately 1.5 p./lO 11.betneen the alpha hydroxy and alpha ether methylene hydrogens, with the ether type having the greater shift (Figure 6). A study of the trvo types of oxymethylene groups in the same aliphatic molecule should show 11-hether this difference is real. The following data were obtained from the spectrum of 2-ethoxyethanol: CHa-CH?-O-CH*-CHr-OH U
VOL. 31,
b
c
NO. 1, JANUARY 1959
63
I I I I
I l l 1
I I I I
I I I I
I l l 1
-
R e f e r e n c e GrouDs: -COOH
ACIDIC H
I I I I
I I I I
{
I I I I
I I I I
I I I I
I I I I
I l l 1
I I I I
I I I I
a n d -COOR
?
-OH,'
MONOCARBOXYLIC ACIDS
DMS
DMF
POL YCARBOXYLIC ACIDS in solvent indicated
1,q-D
A L I P H A T I C ALDEHYDES AND KETONES R e f e r e n c e G r o u p s : -CHO
and
Pf
Q
- CH3 -CH2-
>CO
I
I
ALDEHYDIC H
A L I PHATIC ALCOHOLS AND E T H E R S R e f e r e n c e Groups: -OH a n d - 0 -
ALCOHOLIC H
A L I P H A T I C ESTERS
a
-CH3 TOALCOHOLS
OF A L K Y L ACIDS (ALCOHOL MOIETY ONLY)
Ref e r e n c e G r o u p s : - 0 O C - A l k y l
B 7+ I=
I
-
=
- CH3
a
B
I
II
a
-CHz-
W
P I
7+
Y 1
~~
A L I P H A T I C ESTERS
OF AROMATIC
ACIDS (ALCOHOL MOIETY ONLY)
-en3
Reference G r o w : -0OC-Arom
-CHz-
Figure 6.
Table 111.
Line No. 1 2
3 4 5
6 7
8 9
10 11
12 13 14
15 16 17 18
19 20 21
Compound Succinic acid Glutaric acid Tartaric acid Pimelic acid 3-OH-2 cyclohexene-1-one o-Toluic acid m-Toluic acid 2,4-Di Me benzoic acid 2,5-Di Me benzoic acid 3,4-Di Me benzoic acid 2,4,6-Tri Me benzoic acid p-Isopropyl benzoic acid lJ2-Benzene dicarb. acid 1,3-Benzene dicarb. acid o-Methoxybenzoic acid p-Xethoxybenzoic acid Di Me isophthalate Di Me isophthalate 2 4 6-Tri &leacetophenone &&one Quinone
22 23 24 25 26
a
a I
I
6
I B
I
Y
1
Hydrogen magnetic resonance chemical shifts
Relative Errors Introduced b y Use of Different Solvents and Standards
Solvents" DMF, DMS D l l F . 1.4-D DMF; 1&D, MeOH DMF, MeOH Cm, DMF, 1,4-D A, DRIF, 1,4-D A, DRIF, 1,4-D A. DMF. 1.4-D. 3IeOH
A. Cm A: Cm(C)
Xone (1,4-D), HMDS A, Cm, 1,4-D, DRIS, D M F A(C), Cm(C), 1,4-D(C),D?VIS(C),DMF(C)
Av. Value and (Range) of Chemical Shift in Parts per 10 Million 24.4(0.3) 25.2(0.3) 26. S(O.1) 13.8(0.7) 25.1(0.8) 28.9(0.8) lO.O(O.7) 25.6(0.6) 0.4(0.5) 23,5(0,6) -2.9(1.6) 0.3( 1.3) 24.9(0.7) - 1.8(1.2) -2.1(0.6) 1.O i l . 2 ) 1.8(0.8) 23.810.8) 25.2i0.7) 23. $1.2) 24.9(2 , o j -2.0( 1.3) 2.5.210.41 1.3i0.1) -1.7(0.4) 2 .q o .5 ) 24. ?io. Si 25.2(0.5) -0.7( 1.4) 22,6(0.7) 29. i ( O . 6 ) -3.4(0.4) - 1.5(0.4) -5.8(0.6) -3.5( 1 . 4 ) 1.4(0.5) 17.5(0.5) -2.3( 1.8) 17.S(0.2) 2.1(0.8) -3.412.61 -R . iio . I i 17.8(0.5) 16.3(2.0) -6 3(2 4) 2.8(0.6) 3.2( 1.6) 0,8(3.1) 1.3(1.4)c 1.9(1.6) -2.8(0. i ) 2.5(1.0) 2.1(1. O )
Saphthoquinone Cm, HMPA 1,2-Benzenediol A, D M F 4.0(0.2) lJ3-Benzenediol A, DhlF 26.8(1.2) Acetamide RIeOH, W(h) 3.7(1 . O ) A, DMF, MeOH o-Phenylenediamine 3.211.0) 6.4( 1.0) m-Pheny lenediamine 27 A, DMF, MeOH 28 A, DRIF, MeOH p-Phenylenediamine 29 Max. = 3 . 1 Rlin. = 0 . 1 Range summarv ' Abbreviations used for solvents and standards are defined in Table I. When solvent itself was not used as internal standard, compound used as the internal standard is indicated in parenthesis immediately following solvent designation. In spite of these b Pyridine appears to be an undesirable standard because of its reactivity and tendency to shift peaks preferentially. deficiencies, however, it is sometimes useful as a solvent. Omitting data for DMF solvent. DLIF interacts with quinone to form a new peak.
64
ANALYTICAL CHEMISTRY
I I I I
I l l 1
I l l 1
I l l 1
I I I I
I l l 1
I I I I i I I I I
1 1 1 1
1 1 1 1
1 1 1 1
1 1 1 1
1 1 1 1
i l l 1
ALICYCLIC KETONES
-CH,
Reference Group: X O
as
H ON RING
No. Carbons in r i m3- 6 '
ii"at:
e+
a
e+
ring
6 ,!
6
ALICYCLIC ALCOHOLS -CH3
Reference Group. -OH
H O N RING CYCLIC ETHERS, S A T U R A T E RINGS R e f e r e n c e Atom: -0-
a
=
ALCOHOLIC H
l a to
CH
- CH,
3 - M E M B E R E D RlNG
ring
B*
-CH,-
I CH,
n
i
I a
i n ring
t o ring
02
5 - M E M B E R E D RING
I a
[ :l
6 - M E M B E R E D RING.
-CH,-
a2 a5 hCa
IN RING
a2
IN RING
-CH2- IN RING
I
aB I
azly2
FURANS
-CH,
R e f e r e n c e Atom -0-
ii I II -70
-
-40
-30
Figure 7.
RIethylene Type a (a-0-) b ( r O - , 0-OH) c (a-OH, B-O-)
Chem. Shift, p./10 11. from Bz
Chem. Shift from c
35.3 35.6 34.2
+1.1 +1.4 0
The chemical shift of the alpha ether methylene is 1.1 to 1.4 p./10 11. greater than t h a t of the a-hydroxymethylene, hich agrees well with the value predicted from the individual compounds. I n 2-ethoxyethanol, however, the entire spectrum is shifted about 4 p./lO hf. to lon-er field positions because of the presence of tlyo oxygens in such a small molecule. Another check of this type is afforded by comparison of the chemical shifts of the methylene hydrogens in -CH2C1 and in -CH20H groups. Using the data obtained for the alcohols as an average, the shift charts (Figures 4 and 10) indicate the relative shift between the CY- chloro- and a-hydroxymethylenes should be of the order of 0.8 p./lO U. on the average, with the a-chloromethylene having the larger shift. Comparison of the spectra of n-butyl alcohol and n-hutvl chloride indicates
l a 10-0-
1 1 1 1 1 I 1 1 1 1 1 1 I I J 30
- 20 -10 0 10 20 PARTS PER 10 MILLION FROM BENZENE
6
I a
to ring
H ON RING
I
-
I I I I I I I I I I II I I I I I I I I I I I I I I I
1 1 1 1 I I 60 -50
B
CH, H ON RING
CYCLIC E S T E R S ( L A C T O N E S )
to r i n g
f
I
l a toring at0.co.l I 8 10-0- a-co-
IIIII IIIIIIIIIIIIIII 40
50
60
70
Hydrogen magnetic resonance chemical shifts
Table IV. Chemical Shifts Measured b y Humble Method Compared with Those Measured a t Low Concentration in Carbon Tetrachloride Using Tetramethylsilane as Internal Standard
Compound Benzene Ethylbenzene Ring Methylene Bibenzyl Ring Methvlene p-Xy1en"e Ring Cyclo-octatetraene Methanol Methyl Toluene Ring Methvl Acetone" Acetic acid Cyclohexane
Data of This Study Internal Chem. shift, Data of Tiersa, Solvent standard p./10 M. C.S., p./lO M. Kone Sone CSZ
Kone None Cyclohexane
Sone
Cyclohexane
None None
Toluene Benzene
None
Cvclohexane
None None Yone
Benzene Benzene Benzene
A Chem.
Shift6
0.0
0.0
0.0
0.0 45.3
1.5 46.5
1.5 1.2
0.4 42.4
1.6 43.9
1.2 1.5
1.9 14.7
3.2 15.8
1.3 1.1
39.1
38.9
0.4 48.8 53.1 51.5 55.8
1.7 49.3 51.8 52.0 58.3
-0.1
1.3 0.5 -1.3 0.5 2.5 Average A = 0 . 9
All com ounds run as 1 to 6 vol. 70solutions in CC14, with tetramethylsilane as internal stangard. Chemical shifts converted to p./lO M. from benzene by subtracting 2.734 from Tiers' reported value and multiplying the difference by 10 (36). * Tiers' value minus value from this study.
VOL. 31, NO. 1, JANUARY 1959
e
65
I I I I
1 1 1 1
I I I I
I l l 1
I I I I
AROMATIC ALDEHYDES AND KETONES Reference Groups: - C H O
I I I I
I I I I I I I I I
ANALYTICAL CHEMISTRY
I l l 1
I I I I
I I I I
I I I I
( C = 0 conjugated with ring 1
a n d :CO
I I I I
I I I I
CARBONYL
I I I I
I l l 1
r,ng
I B to r i n g
r r l l l l l r l l l l l I l l l l l I I I I I l l r l I l l l l I l l l l I l l l l l l l l l r l l l l r
a relative shift of 1.4 p./lO i K,with the a-chloromethylene having the larger shift. The relative shift actually found in 2-chloroethanol was 1.7 p./10 M. Comparisons such as these two indicate that the spectral data from which the shift charts were derived are sometimes better than the charts indicate, and that usefulness of the charts might be improved significantly by further study. They also provide some additional evidence t h a t the technique used in obtaining the data is sound. Comparisons of the Humble data with related data obtained by other workers are presented in Tables IV and V. Table IV compares the chemical shifts measured by the Humble technique at high sample concentration using several different internal standards with those measured by Tiers (86) a t low sample concentration in carbon tetrachloride using only tetramethylsilane as the internal standard. Because Tiers' values represent the chemical shifts a t infinite dilution in a magnetically isotropic solvent, the differences between these and the Humble values are attributed to interac-
66
I I I I
tions between sample molecules and between sample and standard a t the high concentrations. The average difference of 0.9 p./10 31. is considered a small price to pay for the higher signalto-noise ratio, speed, and other advantages realized a t high s:mple concentrations. Table V compares the chemical shifts obtained by Humble using varying concentrations of internal standard with those obtained by Corio and Dailey (I?') using uniform 50% solutions of the sample in cyclohexane. Because all the compounds shon n are aromatics, the adverse solvent effects should be a t their worst. The differences noted can be attributed to variations in the selections of band centers and to slightly greater error in the Humble method of measuring the shifts (the side band technique used by Corio and Dailey is considered to be more precise). Except for acetophenone, for which benzene apparently is not as good a standard as cyclohexane, there appears to be no debit which can definitely be attributed to the varying concentrations and types of standards in the Humble samples.
The reliablity of these data s h o m that the NMR technique described here provides a means of identifying a rather narrow chemical shift region with a particular type of hydrogencontaining functional group under a yariety of conditions and in many compound types. A given chemical shift region is not usually exclusive to a single functional group, but the number of groups identifiable with i t is usually small and of such naturc that reasonable choice among the indiyidual groups can be made from other spectral features or from non-XhIR data. This is of considerable value analytically. Use. T h e chemical shift charts can be used t o predict t h e chemical shifts of t h e resonance bands which would be produced by a proposed compound, or to determine the functional groups responsible for the chemical shifts observed in a sample. To predict the spectrum of a proposed compound, designate all the functional groups in that compound according to the scheme in Figure 3, then read the chemical shift for each group from the proper shift chart section or sections. To determine the functional groups
-30 - 20 -10 1 1 1 1 1 1 I I I I I I I 1 1 1
-70 -60 - 50 -40 [ I I I I I I I I I I I I I I I I
0
20 30 I I I I I I I I i
10
I I I I I T I I I I
i
i
40 i
50 ~ ~
~
i
60 70 i ~ 1 i 1 1i 1 i
i
OX Y GE N A T E D AROMATICS, CONTINUED
AROMATIC S U B S T I T U T E D ALIPHATIC ACIDS AND THEIR E S T E R S and -COOR
References. -COOH
' cszcm
-CH2c io ON ARoM'
%!znsed
ring-
ACIDIC
DMF
2'4-D]A~.
L'I
naphthyl
a
8-a
byi I
1
Phenyl
H i s not conjugated with ring 1 a W a
-CH2H ON AROM. RlNG
to ring
1
AROMATIC E S T E R S OF A L I P H A T I C OR AROMATIC ACIDS (ALCOHOL MOIETY ONLY
1 OP
or - 0 O C - A r .
-CH3
Q to r i n g
a IQ
-CH2-
=
H ON AROM. RlNG QUINONES
10
Single r i n g
= 0
References: -00C-Aliph.
I
I
p o s i t i o n i n solvent indicated.
AROMATIC S U B S T I T U T E D A L I P H A T I C K E T O N E S (C.0 Reference: C :
a
Y
to r i n g
H ON QUINONE R l N G H A L O G E N COMPOUNDS
-
CHLOROCYCLOALKANES (CG RING) Reference: -CI
H ON R I N G {
-CH,-CH: Herochlorocyclohexones
-70
1 1 1 1 1 l I I I I I I I I I I l I I l l l l l l l l l l l l l l l l l l l I I I I I I I I I I I I I I I I I I 1 I I I I I 1 1 1 1 1 1 1 - 60 -50 -40 - 30 -20 -10 0 10 20 30 40 50 60 70
PARTS PER 10 MILLION FROM BENZENE
Figure 9.
responsible for the chemical shifts observed in a sample, i t is generally advisable to search all the charts at each chemical shift to be sure t h a t no possibilities are overlooked. Elimination of overlapping possibilities must be made o n the basis of other features of the N M R spectrum, of independent information obtained from the nature of the synthesis, or from other analytical methods. Many times the NMR data plus a knowledge of the source of the
Table V.
Hydrogen magnetic resonance chemical shifts
sample are sufficient t o define the sample molecular structure completely. At other times NMR can provide only a few specific bits of information n hich can be coupled with information supplied by infrared, ultraviolet, mass spectrometry, and gas chromatography, to solve the analytical problem. There can be all degrees of completeness betxeen these extremes. hfany compound types are not represented in the charts and many gaps
exist in the data for some of the compound types included. Much of the missing information can be deduced, however, from a study of the charts and observation of a few additional spectra. For instance, no data are given for the chemical shifts of CH2 and CH groups attached to cyclic olefins (Figure 4). This information can be deduced in several ways. The charts show that chemical shifts of comparable groups fall in the order
Chemical Shifts Measured by Humble Method Compared with Those Measured a t Constant Concentration in Cyclohexane
Compound Nitrobenzene Benzaldehyde Me benzoate Acetophenone Benzoic acid Benzyl chloride Toluene Benzyl alcohol Phenol .4niline
Solvent None Kone None None 1,4-D None None Kone
cs*
Xone
Data from This Study Chem. Shift, p./10 AI.,' Internal Ring H Onlv standard Ortho ALIeta Para Cyclohexane -10.6 -4.7 -6.2 Cyclohexane -3.3 -7.4 -4.6 Cyclohexane -9.5 -2.5 -3.9 -5.8 -1.0 -1.7 Benzene 14-D
dyclohexane Cyclohexane Cyclohexane Benzene Cyclohexane
-7.0 -0.5 0.4 0.3 3.1 7.4
-0.5 -0.5 0.4 0.3 3.1 1.2
-1.8 -0 5 0.4 0.3 3.1 2.4
Data of Corio and D ailey Chem. Shift, p./10 M. Ortho Meta Para -9.7 -7.3 -9.3 -6.3 -6.3* 0.0
-3.0 -2.3 -2.0 -2.7 -l.Ob 0.0
-4.2 -3.7 -2 7 -2.7 -1.7b 0.0
0.7 3.7 7.7
0.7 3.7 1.3
0.7 3.7 4.0 hv. A
1 0
1.0
A Chem. Shift
1.0
=
Ortho
Meta
0.9 0.1 0.2 -0.5 0.7 0.5 0.6 0.4 0.4 0.3
1.7
0.4
Para
1.0
2.0 0.9 1.2
0.4
0.4
0.5 -1.7 -1.0 0.5 0.1 0.5 0.5 0.6 0.6 0.4 0.4 0.4 0.4 0.1 -1.1 -
All samples except benzoic acid observed at. 50y0 concentration in cyclohexane using cyclohexane as internal standard ( 1 7 ) . Signs reversed to conform to Humble convention. In acetone solvent using acetone as internal standard.
VOL. 31, NO. 1, JANUARY 1959
67
~
i
-50
-40
- 30
-20
-!O
0
10
30
20
50
40
60
70
HALOGEN COMPOUNDS, CONTINUED CHLOROALKANES ( A L I P H A T I C CHLORIDES 1
-CHz a3
Reference.
R e f e r e n c e : - C l ( a , B ) a n d -CH2Cl(o,rn,p)
H ON AROM. RING ~
B R 0 MOA L K Y L A R 0 M A T I CS
-CHz
I I
I
-
I
a
-
8
I
I
OP
II
a
-CHz-
a
Q
to ring
to ring
0,
-CH3
?map*
I ! ~ Q I Or i n g
a
-CHzH ON AROM RING
I a to
ring
lima'
methvl arOuD
R e f e r e n c e : -CI
a
-CHZOLEFINIC H
CH, > CH2 > CH, the actual differences depending on the compound type. The chart for the olefins shows that the difference in comparable resonances for CH3, CH,, and C H in this series is about 1 pJ10 11. For the cycle olefins, then, CH2 and C H shifts can be estimated by subtracting 1 and 2 p./lO AI., respectively, from the shifts of the proper methyl groups. A less accurate but sometimes necessary technique assumes additivity of the differences in chemical shift between paraffinic methyl groups and all other functional groups. The chemical shift values so estimated are usually a little lower than actually found by experiment, but are close enough for rough identification purposes. Figure 16, B, shows that the average chemical shift of paraffinic methyl groups is 62.5 p./lO M. Suppose it is desired to determine the chemical shift of a CH2 group which is alpha to an ether oxygen and also alpha to a carbonyl group (-OC-CHz-0-). Figure 6 shows the chemical shift of CHz-0to average 38.5 p./10 JI., and that of CHz-COto average 48.5 p./lO 11. The CH2-COshift is 62.5 - 48.5 = 14.0 p./lO M. less than that of the paraffinic methyl group. The desired
68
I
Y
7
-CH3
Reference - B r ( a , B ) and -CH2Br(o,rn,p)
*Shielded bv o d i o c e n t CHLORO OLEFINS
I
8rY2
-CH3
-I
CHLOROALKYL AROMATICS
~~
I
Y2 8
I
7
- Br
IODOALKANES Reference:
-
aa
-CH:
I
BROMOALKANES
b2
-CH3
Reference -CI
ANALYTICAL CHEMISTRY
{
TERMINAL NON- T E R M I N A L
laolefinic
a8
7
I
Terminal
L
shift of -0C-CH2-0 is then estimated as 38.5 - 14.0 = 24.5 p./lO hl. The shift for CH, cy2 to ether oxygen, which would be expected to be less than that for -0C-CHz-O--, is shown as 26.5 p./lO M. Thus the estimated value appears to be 3 or 4 p./lO AI. too low, but this is within the limits prescribed for reasonably good identification. INFORMATION AVAILABLE IN CHARTS
I n addition to the most obvious relationship of hydrogen chemical shift to type and position of electronegative group, the chemical shift charts show phenomena which are important to both the analyst and the chemist. A study of these phenomena should enable the research worker to devise means of using N N R to solve more of his problems. Chemical Shifts of HydrogenBonded Hydrogens. The marked shifting of the resonance positions of acidic and phenolic hydrogens with a change in solvent is shown in Figures 6 to 9 and 11. This marked shifting of resonance with change of either the type or the concentration of solvent is typical of hydrogens which are easily hydrogen-bonded, such as alcoholic,
acidic, amine, and phenolic hydrogens. It is seldom observed for hydrogens which cannot form hydrogen bonds for steric or chemical reasons. It appears, therefore, that this phenomenon is useful for identifying such hydrogens and for studying hydrogen bonding (15, 25). Because of rapid proton exchange, the resonances of all reactiye OH hydrogens in a sample occur a t the same position when the p H of the sample is outside the neutral range (outside about 6 to 8 pH.). S o exceptions to this rule have been observed in the many samples of different types which have been studied here. The actual position depends on the relative amounts of the various types of OH hydrogen (alcoholic, acidic. phenolic, water, caustic) present as well as on the total OH concentration ( 8 ) . -4 convenient way to test for O H is to add a small amount of acid or alcohol to the sample, depending on the location of the peak suspected of being produced by OH hydrogen, and to rerun the spectrum. If there is a marked shifting of one of the sample peaks accompanied by an increase in intensity of this same peak, and if no additional peak Ivhich can be attributed to the added OH hydrogen appears, the peak which shifts is identi-
NITROGEN COMPOUNDS ALIPHATIC AND CYCLIC AMINES
B I
-CH,
R e f e r e n c e -NY,
a I
-CH,-
AMINE H mp
AROMATIC AMINES ( N Q t o r i n g )
I1
R e f e r e n c e -NH,
ra p m
I
PYRIDINER e f e r e n c e =NReference
0
I
-N02
ALIPHATIC AMIDES, ACID MOIETY R e f e r e n c e -CONR,
-
ALIPHATIC AMIDES, AMINE MOIETY R e f e r e n c e >NCOR
AROMATIC AMIDE (DIPHENYL FORMAMIDE) H ON AROM. RING I
ozaop
I
p m
H ON RING
DIAMINES
H ON RING
I I
-
MONOAMINES
I
m om
0
NITROBENZENE
0
B I
AMINE H
H ON RING
I I
-CH,
a I
ALDEHYDIC H OF FORMAMIDES
-
&
- CH, -CH,H O N N
B
I
a I
I
ALDEHYDIC H OF FORMAMIDE
SILICON COMPOUNDS A L IP HAT I C SI L O X ANE S
-GH,
Reference ~ S I - O - S I $
-70
a I
1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I I I I I I I I I I I I I l I I I I l I I I I I I I I I I I I I I I l I I I l l l l l l l l l l l - 60 -50 - 40 -30 -20 -10 0 10 20 30 40 50 60 70
PARTS PER 10 MILLION FROM BENZENE Figure 1 1.
fied as due to OH hydrogen. If, on the other hand, there is little or no shifting of any of the sample peaks and if a new peak appears which can be attributed to the added OH hydrogen, it is concluded that there is no reactive OH hydrogen in the sample. It is considered possible that OH hydrogens in some samples could be so tightly hydrogen bonded within the molecule or so sterically hindered that they vvould be unable to exchange rapidly with the added OH hydrogens and n-ould not be identifiable by this technique. So far, hoir ever, no such hydrogens have been observed. The relationship betveen solvent and resonance position for alcoholic and amine hydrogens is not shown on the charts because it was not studied in sufficient detail. Aldehydic and thiolic hydrogens do not exhibit this type of resonance shift, indicating that thcy are not hydrogen bonded. Because the carboxylic acids were nearly all observed as saturated solutions in the various solvents, the resonance shifts indicated for the acidic hydrogens include both the effects of changing solvent and changing dilution. Time and equipment limitations pre-
Hydrogen magnetic resonance chemical shifts
vented a separation of these t n o variables in this study. Diamagnetic Shielding by Methyl Groups. Methyl groups on aromatic or olefinic structures tend to shift the resonances of adjacent hydrogen groups to higher applied field positions. Figure 5 shows the shielding effect of methyl groups on adjacent methyl groups and on the aromatic ring hydrogens for the methylated benzenes. The effect (attributed to donation of negative charge by the methyls) tends to extend all around the ring so t h a t the resonances of all the ring hydrogens shift t o higher field positions. The effect of methyl shielding is shown for methyls in Figure 10, for aromatic ring and phenolic -hydrogens in Figures 8 and 12, and for olefinic hydrogens in Figure 4. Similar shielding effects appear t o be produced by ethyl and propyl groups, but the data are not so clear and consistent as for the methyl groups. It may be that the shielding effects of the larger alkyl groups are masked by other factors not controlled in this study. Equatorial vs. Polar Substitution of Cyclohexanes a n d Cyclohexenes. I n
methylated cyclohexanes and cyclohexenes, it appears t h a t methyl groups in polar positions should be shielded more by adjacent hydrogen atoms and by the ring itself than methyl groups in the equatorial positions. The tentative shift in rebonancc positions between the equatorial and polar methyls, selected after a study of mono-, di-, and trimethylcyclohexanes, and mono- and dimethylcyclohexenes is s h o m in Figure 4. Olefinic Proton Types. Figure 4 shons t h a t the average chemical shifts of mono-olefinic, conjugated diolefinic, and allenic hydrogens are reasonably well separated, and t h a t there is an even greater separation between the average chemical shifts for terminal and nonterminal olefinic hydrogens of the same type. The separation betn een the shifts of terminal and nonterminal olefinic hydrogens is also shown in Figures 5 and 13. Under some conditions these differences should be useful for distinguishing among thesc olefin types. Effect of Alicyclic Ring Size on Chemical Shift. Gutowsky et al. (23) have reported t h a t for cyclic ethers, cyclic sulfides, and cyclic amines the VOL. 31, NO. 1, JANUARY 1959
69
-70
-60
-50
- 30
-40
- 20
20
10
-10
30
50
40
60
70
SULFUR COMPOUNDS ALIPHATIC T H I O L S Reference
B 76
-CH,
-SH
I II
-
a I
-CH2a I
-CH
