work were provided by E. M. Amir, D. G‘ I* p’ and N’
w’
Mitchell.
LITERATURE CITED
(1) Alexander, S., J. Chem. Phys. 32, 1701
(1960). Anet, F.A. L., Can. J. Chem. 39,2262 (1961). (3) Bartz K. W.,Chamberlain, N. F., ANAL. HEM. 36,2151 (1964).
(2)
(4) Bothner-By, A. A., et al., J. Am. Chem. SOC.84,2748 (1962). (5) Brugel, W. von, et al., Electrochem. 64, 1121 (1960). (6) Chamberlain, N. I?., ANAL. CHEM. 31, 56 (1959). (7) Corio, P. L., Chem. Rev. 60, 363 (1960). (8) Fasenden, R. WV Waughi J. s . ~ J. Chem.Phys. 30,944 (1959). (9)CHEM. Francis, 35,1363 S. A.,(1963). Archer, E. D.,ANAL. (10) Golub, M. A., et ul., J . Am. C h . SOC.84,4981 (1962).
(11) Jackman, L.M., “Nuclear Magnetic Resonance Spectroscopy,” p, 87, Pergamon Press, New York, 1959. (12) Reddy, G. S., Goldstem, J. H., J . Am. Chem. Soc. 83,2045 (1961). (13) Schaeffer, T.,Can. J. Chem. 40, 1 (1962). (14)Tiers, G.V. D., J . Phys. Chem. 62, 1151 (1958). (15) Tiers, G. V. D., Minnesota Mining and Manufacturing Co., St. Paul, Minn. private communication, March 1958. RECEIVEDfor review June 15, 1966. Accepted July 21,1966.
Determination of Components in Phenol Mixtures by Nuclear Magnetic Resonance MARTIN W. DIETRICH, JAMES
S. NASH,’
and ROBERT E. KELLER
Research Department, Organic Chemicals Division, Monsanto Co., St. Louis, Mo. Many mixtures of phenols in hexamethylphosphoramide were found to give NMR spectra containing a well resolved hydroxyl peak for each component. These peaks occur in the region 8 to 13 p.p.m. and are free from interference due to aromatic proton absorption. The chemical shift of a particular phenol is not affected by concentration or by the presence of other phenols. The hydroxyl peaks of ortho-, meta-, and para-alkyl phenols, as well as certain polyalkyl phenols, occur in characteristic chemical shift regions. A linear plot is obtained when the hydroxyl chemical shift of meta- or para-substituted phenols is plotted against Hammett’s constant for the substituent. A similar plot is obtained when the hydroxyl chemical shift for ortho-substituted phenols is plotted against Taft’s constant for the substituent. These observed correlations provide a basis for identifying and measuring components in mixtures of phenols.
T
identification of components in mixtures of phenols has been investigated by several techniques. Although excellent results are reported in specific cases, each method has limitations. Gas chromatography probably is the most extensively used of these techniques, particularly after conversion to the trimethylsilyl ethers ( 7 ) . Although excellent separations are obtained, a subsequent identification of the chromatographic peaks is needed. Also, in the case of highly hindered phenols, quantitative conversion to the trimethylsilyl ether can prove difficult (4). Infrared spectrometry is an excellent HE
Present address: University of Kentucky, Lexington, Ky.
63 177
technique for the identification of individual phenols. Among other spectral features, characteristic absorption patterns (18) in the 5.0- to 6.0-micron region are often used to identify the aromatic substitution pattern. Mixtures of phenols, however, often display extensive peak overlap in this and other spectral regions used for identification, making analysis difficult. Reference to spectra of the pure components may be necessary for final identification. Several nuclear magnetic resonance (NMR) procedures for characterizing phenols have been reported. Characteristic patterns for the aromatic proton absorption and for the absorption of the protons on the carbon atoms alpha to the aromatic ring can yield information on the ortho-para ratio in alkyl phenols (3). For alkyl phenols which are not highly hindered, acetate derivatives can also be prepared. Distinct acetate methyl peaks are obtained for the ortho and pura isomers (8) providing a basis for the determination of this isomer ratio. Characteristic hydroxyl chemical shifts for meta- and para-substituted phenols in dimethyl sulfoxide (10) may also prove useful for isomer analysis. This report describes a procedure for the identification of phenols in mixtures of phenols, both alkyl and nonalkyl, using characteristic hydroxyl chemical shifts in hexamethylphosphoramide (HMPA). These mixtures often give well resolved hydroxyl peaks for each component, making quantitative analysis possible. EXPERIMENTAL
All phenols used in this study were obtained from commercial sources and were used without additional purifica-
tion. Phenol purity was determined from examination of the hydroxyl region of the NMR spectra in HMPA. No data are included for phenols which were found to be less than 90% pure by this procedure. The HMPA available from commercial sources (Borden Co., Eastman Kodak Co., and Aldrich Co.) was found to contain varying amounts of basic impurities. Phenols in these solvents display exchange broadened hydroxyl N M R peaks. Reduced pressure distillation gave a neutral material of low conductivity. However, broadened hydroxyl peaks were again observed. This broadening may arise from low levels of base not removed by distillation. Alternately, this broadening may reflect the natural dissociation of phenols in HMPA, with the resulting phenol-phenate proton exchange leading to hydroxyl line broadening. HMPA giving sharp phenolic hydroxyl peaks was obtained upon the addition of 250 mg. of Mallinckrodt AR ortho-boric acid to 100 ml. of distilled HMPA (Eastman, ca. 50% distillation center cut). This material was stored over Linde molecular sieve #4A before use. Boric acid was chosen because it is expected to react with residual amine impurities (15) as well as suppress phenol dissociation. Because of the wide variation observed in the level of impurities in HMPA, a slight change in the boric acid concentration may be necessary to obtain optimum resolution. All N M R measurements were made with a Varian Assoc. A-60 N M R spectrometer equipped with a variable temperature probe. Unless specified, NMR measurements were made a t the ambient probe temperature determined to be 40’ C. Spectra were obtained a t a sweep rate of 4.0 c.p.s./second. Chemical shift values are reported with reference to TMS = 0 and represent the average of at least two measurements. They are considered accurate to within *0.03 p.p.m. Unless indicated, all VOL 38, NO. 1 1 , OCTOBER 1966
1479
region 6,5 to 8.0 p.p.m. typical for aromatic pratons. Also, t h e phenolic proton peak must have a reasonably small line width. Because there are few structural units that have NMR peaks below about 8.0 p.p.m., an attempt wm made to find B solvent system in which phenolic protons give peaks in this region while remaining sharp. Most phenolic protons in the common NMR solvents give peaks above 8.0 p.p.m. Solvents were studied which might be expected to cause a low field shift for the phenolic proton through hydrogen bonding (IS). For this study, solvents were chosen which might be expected to act as Lewis bases toward phenols. No bases containing exchangeable hydrogens were chosen to avoid the complications to be expected with such compounds. Table I shows the chemical shift obtained for the hydroxyl proton of 2,6-di-tertbutylphenol in carbon tetrachloride containing various bases. A low mole fraction base was chosen because preliminary work indicated that, at high mole fraction base, some bases cause line broadening. This phenol was chosen because the high degree of hindrance about the hydroxyl group is expected to make hydrogen bonding especially difficult. Results showed that, of the 14 bases studied, hexamethylphosphoramide (HMPA) caused the largest shift of the phenolic hydroxyl signal. Under these conditions, however, the change in chemical shift wap small compared to the change desired. To increase the chemical shift change, this phenol was run as a 0.60M solution in HMP.4. A sharp hydroxyl peak a t 6 = 8.03 p.p.m. was obtained. This is
a I
I
12.0
10.0
4 .O
6.0
8.0 J(F?!?Ml
Figure 1. NMR spectrum of an equimolar mixture of phenol (2), 2-tert-butylphenol (1 ), 2-6-di-methylphenol (3), 2-methyl-6-tert-butylphenol (4), and 2,6-diferf-butylphenol (5) In carbon tetrachloride In hexamethylphosphoramide
a. b.
hydroxyl peak line widths, expressed as full line width a t one-half maximum peak height, are less than 2 C.P.S.
on the hydroxyl proton signal, this signal must occur in a region free of other absorption. I n particular, the hydroxyl peak must not occur in the
RESULTS
Choice of Solvent. T o develop a satisfactory N M R procedure for characterizing phenolic materials based Table 1. Effect of Bases on Chemical Shift of 2,6-Di-tert-butylphenol~
I
23
bOH ( P .P .m .
Base added from TMS) None 4.97 Triethylamine 4.97 Thiophene 4.97 Tetrahydrothiophene 4.97 Ethyl acetate 4.98 Acetonitrile 4.98 Ethyl carbonate 4.98 Aceto henone 4.99 Tetraf ydrof uran 5.02 Acetone 5.02 5.17 N,N-Dimethyl formamide Dimethyl sulfoxide 5.18 Pyridine 5.20 Trimethyl phosphate 5.25 5.38 Hexamethylphosphoramide All samples run in carbon tetrachloride as 0.60M in 2,6-di-tert-butylphenol with a mole fraction base* of 0.30. b Mole fraction base = Moles base Moles base + Moles 2,6-di-tert-butylphenol 0
1480
ANALYTICAL CHEMISTRY
I
12.0
I
I
8*o b(RRM,
10.0
6 .O
Figure 2. NMR spectrum of an approximately equimolar mixture phenol (2), 3-methoxyphenol ( l ) , and 4-methoxyphenol (3) a. b.
In carbon tetrachloride In hexamethylphosphoramide
4 .O
of
2-methoxy-
-~ ~
~~~~
~
~
~~
Table 11. Chemical Shifts of Monoalkyl Phenols in Hexamethylphosphoramide 6OH (p.p.m. to TMS) Substituent Ortho Me& Para
None 10.30 Methyl" 10.22 10.15 10.02 Ethyl 10.20 n-Propyl 10.18 10.03 iso-Propyl" 10.22 10.15 10.03 sec-Butyl 10.17 10.02 tert-Butyl" 10.33 10.12 10.07 n-Amyl 10.05 tert-Amyl 10.01 Cyclohexyl 10.15 10.07 n-Pentadecyl 10.12 Dodecyl 10.03 a Three peaks of an equimolar ortho: mefa:para mixture at least 75% resolved.
below the region of most aromatic hydrogen absorption. Alkyl phenols with varying degrees of steric hindrance about the hydroxyl group were examined to verify this effect. Phenols substituted with groups other than alkyl were also studied. Chemical Shifts in HMPA. The low field portion of t h e N M R spectrum of a n equimolar mixture of phenol, 2-tert-butylphenol, 2,6-dimethylphenol, 2 - methyl - 6 - tert butylphenol and 2,6-di-brtbutylphenol in carbon tetrachloride is shown in Figure la. As is typical for such mixtures, poorly resolved hydroxyl signals are observed in the region 4.4 to 5.1 p.p.m. Additional hydroxyl absorption may occur in the region 6.5 to 7.5 p.p.m., which is obscured by the aromatic absorption. Figure l b shows the same portion of the N M R spectrum of this phenol mixture in HMPA. Minor changes are obtained in the aromatic region (6.5 to 7.5 p.p.m.). High field alkyl (0.5 to 2.5 p.p.m.) and solvent (6 = 2.6 p.p.m., doublet) peaks are not shown. Although complete resolution is not obtained, a well defined phenolic hydroxyl peak is observed for each component. All hydroxyl peaks are in the region 8.0 to 10.2 p.p.m., which is below the aromatic proton absorption. Identification of the hydroxyl peaks in this spectrum was made by addition of the individual components. As was observed for 2,6-di-tert-butylphenol1the hydroxyl peak of each component is comparatively sharp (less than ca. 2 c.P.s.). Comparison to spectra of the individual components in HMPA showed that the chemical shifts are not affected by the presence of other phenols. The phenolic hydroxyl chemical shift was found also to be independent of concentration over the range 0.05 to 1.OM. At higher concentrations, some line broadening occurs. Many phenols containing other functional groups also give sharp phenolic hydroxyl signals in HMPA.
The low field portions of the N M R spectra of an equimolar mixture of 2methoxyphenol, Smethoxyphenol, and 4-methoxyphenol in carbon tetrachloride and in HMPA are shown in Figure 2. In carbon tetrachloride, no peaks are observed which are readily assignable to hydroxyl. These peaks are presumably obscured by the aromatic proton absorption. As was observed for mixtures of alkylphenols in HMPA, a well resolved hydroxyl peak is obtained for each component. High field methoxyl and solvent peaks are not shown. Again, low field shifts of the hydroxyl peaks are obtained in HMPA due to strong phenol-HMPA hydrogen bonding. The minor peaks at 6 = 6.3 p.p.m. and 6 = 9.0 p.p.m. are due t o the boric acid added to the HMPA. The occurrence in HMPA of sharp phenolic hydroxyl peaks which are not concentration dependent suggests that this may provide a method for identifying components in mixtures of phenols. To determine the utility of this procedure, N M R spectra of a series of substituted phenols were obtained. The phenols studied represent examples with a wide variation in steric hindrance about the hydroxyl group. Examples were also examined with structural units of widely varying electron donating or withdrawing properties. Table I1 summarizes the phenolic chemical shifts observed for phenol and monoalkyl phenols. Table I11 summarizes the data obtained from other monosubstituted phenols. Table IV summarizes the data obtained from polysubstituted phenols.
Table IV.
Table 111. Chemical Shifts of Monosubstituted Phenols Other than Alkyl Phenols in Hexamethylphosphoramide
subaOH (p.p.m. to TMS) stituent Ortho Metu Para None 10.30 Acetyl 11.88 11.53 Amino 9.07" Bromo" 11.27 10.88 10.75 Carbox Formylr~f lle67 10e95 lie@ Iodo 11.35 Methoxy" 9.92 10.30 9.80 Nitrob 12.1d 11.57" ll.gd Phenoxr 10.63 10.35 Phenyl 10.57 10.47 10.53 Trifluoromethyl 11.12 "Three peaks of an equimolar ortho: meta: ara mixture at least 75% resolved. * T%ee peaks of an equimolar ortho: mefa: ara mixture less than 75% r e solvel c Full line width at half maximum peak height between 2 and 10 C.P.S. d Full line width at half maximum peak height greater than 10 C.P.S. e Broad exchange averaged OH signal with area of two hydrogens per molecule. Three aldehyde peaks of an equimolar ortho:Ineta:para mixture fully resolved.
Sharp hydroxyl peaks ( h e width less than 2 c.p.5.) were obtained for most of the examples studied. All phenolic peaks occurred at lower field than typical aromatic proton peaks. Some phenols containing strongly electron withdrawing groups gave broadened hydroxyl peaks. Phenols containing other structural units with exchangeable protons also gave broadened hydroxyl
Chemical Shifts of Polysubstituted Phenols in Hexamethylphosphoramide
6OH
2 tert-Butyl tertButy1 tert-Butyl
tert-Butyl Methyl Methoxy Methyl iso-Propyl Methyl Methyl Methyl sec-Butyl Methyl Methyl iso-Propyl ~~
Methyl
3
Substituent positions 4 tertButy1 Methyl DimethylAmino Methyl
Methyl
5
Methyl Methyl
Methyl Methyl Methyl Methyl Methyl Methyl
Methyl Methyl seeButyl Methyl Methyl
Methyl
6 tert-Butyl tertButyl tertButyl
tert-Butyl Methyl Methoxy tertButy1 iso-Propyl tert-Butyl Methyl Ethyl
Methyl Methyl Methyl
(P.P*m. to TMS) 7.83 7.83 7.92 8.03 8.90 8.93 8.93 9.07 9.13 9.20 9.80 9.80 9.90 9.93b 9.95 9.97 10.01 10.02 10.0s
Chloro Methyl Methoxyl Formyl Chloro Chloro Chloro Chloro Chloro a Hydroxyl peak full line width at half maximum peak height greater than Relative positions in the dimethyl series confirmed by addition of the components.
10.34 11.4" 12.24 10 c.p:s. indivldual
VOL 38, NO. 11, OCTOBER 1966
1481
PlH
I 14.0
I
I
12.0
10.0 (BIM. lo TMSl
J0"
Figure 3. NMR spectra of 4-hydroxybenzoic various temperatures
peaks. In the case of the carboxy phenols, a broad exchange averaged hydroxyl peak resulting from both the phenol and acid protons is obtained. The formyl phenols gave two peaks below the aromatic absorption. The hydroxyl peak was identified by the slight line broadening observed for one of these peaks. Also, formyl protons were found to have similar chemical shifts in carbon tetrachloride and in HMPA. Variable Temperature Studies. A decrease in temperature caused a decrease of t h e hydroxyl peak line width both for individual phenols and phenol mixtures in HMPA. To prevent sample freezing, the addition of ca. 10% chloroform-d is necessary to obtain spectra below 0" C. The presence of this level of chloroform-d causes no change in the hydroxyl peak line width or chemical shift. Conversely, an increase in temperature causes an appreciable hydroxyl peak line broadening. Figure 3 shows the NMR spectrum of Chydroxybenzoic acid in HMPA at various temperatures. At 40" C., a broad hydroxyl peak with a n area of two protons is obtained from both hydroxyl environments. An increase in temperature above 40" C. causes a progressive sharpening of the hydroxyl peak. This is indicative of increasingly rapid exchange, with an approaching of the fast exchange limit case. At low temperatures, an appreciable decrease in the proton exchange rate is indicated. At -40" C., distinct peaks are obtained 1482
ANALYTICAL CHEMISTRY
I
I 8.0
6.0
acid
in
HMPA a t
,
for the phenolic OH (6 = 11.1 p.p.m. 1H) and for the carboxy OH (6 = 12.9 p.p.m., 1 H). Because the carboxy proton is expected to occur a t lower field, the peak a t 6 = 12.9 p.p.m. is assigned to the latter. The greater line width of this peak also supports this assignment. DISCUSSION
Phenols with Alkyl Substituents. The hydroxyl chemical shift data for the alkyl phenols reported in Tables I1 and IV are summarized in a correla11.0 TETRAALKYL PHENOLS
TRIALKYL
,
17.0
tion chart shown in Figure 4. Primary division of the data was made on the basis of the number of alkyl groups per aromatic ring. For the monoalkyl phenols, a further classification is established according to position of the alkyl group on the aromatic nucleus. Because of limited data, no attempt was made to extend this classification to polyalkylated phenols. The chemical shift ranges shown in Figure 4 can be used to determine the composition of alkyl phenol mixtures. The chemical shifts are found in three well separated regions. Hydroxyl peaks in the range ca. 9.8 to 10.3 p.p.m. are attributable to monoalkyl phenols and polyalkyl phenols which do not have substituents on both the 2 and 6 positions. Only a slight dependence of the hydroxyl chemical shift on the number of substituents was observed. No characteristic ranges for specific substitution patterns are evident other than for the monoakyl phenols. Hydroxyl peaks in the range ca. 8.9 to 9.2 p.p.m. are attributable to polyalkyl phenols containing substituents on both the 2 and 6 positions. One or both of the substituents, however, must be smaller or less highly branched than the tert butyl group. Hydroxyl peaks in the range ca. 8.9 to 9.2 p.p.m. are attributable to polyalkyl phenols containing substituents as large and highly branched as the tertbutyl group in both mtho positions. I t is often difficult t o identify individual peaks from complex phenol mixtures containing mono- and polyalkyl phenols. For such mixtures, however, it is possible to determine the average degree of aromatic substitution by measurement of the area of the aromatic proton peaks and the total area of the phenolic proton peaks. The
,
"0
,
,
,
;
PHENOLS
DIALKYL PHENOLS
MONOALKYL PHENOLS -PARA
- META
1
,
,:
~
,
,
I(71
-ORTHO 11.0
9 .o
10.0 JOH.
0 .O
I
(REM. to TMS)
Figure 4. Structure correlation chart for hydroxyl protons of alkyl phenols in hexamethylphosphoramide
ratio of these peak areas can be useful in identifying the types of phenols present. N M R spectra in chloroformd can also provide useful information about the identity of the alkyl substituents. For the monoalkyl phenols studied, three distinct absorption regions are observed: ortho, 10.15 to 10.33 p.p.m.; meta, 10.12 to 10.15 p.p.m,; para, 10.01 to 10.07 p.p.m. These data presented as bar graphs in Figure 4 allow ready identification of the substitution position of monoalkyl phenols in mixtures. Some overlap can be expected between peaks for certain ortho- and meta-alkyl phenols. This is not a serious limitation because the alkylation of phenols normally gives only a small amount of the meta isomers. The presence of certain polyalkyl phenols, however, may prevent this identification. For simple mixtures containing only the ortholmetalpara isomers of a single alkyl group, a quantitative analysis may also be possible. The three ortholmetalpara systems included in Table I1 gave hydroxyl peaks at least 75% resolved in equimolar mixtures. All the systems studied gave fully resolved ortho and para hydroxyl peaks in equimolar mixtures. Some earlier spectrometric (12) and N M R (16) studies have indicated a progressive increase in steric hindrance about the hydroxyl group of alkyl phenols with ortho-substituent size and degree of chain branching. Our results obtained using HMPA show that the degree of steric hindrance for alkyl phenols with one ortho substituent is relatively independent of substituent size or degree of chain branching. Alkyl phenols with two ortho substituents show a much greater degree of hindrance. The substituent size and degree of chain branching have little effect unless both substituents are tertbutyl. 2,6Di-tert-butylphenol displays a much larger degree of steric hindrance than 2-methyl-6-tert-butylphenol. The apparent discrepancy between our conclusions and those of the earlier works cited presumably arises because of a difference in the hydrogen bonding systems involved. In HMPA, the hydrogen bonding arises from phenolsolvent association rather than phenolphenol association. Phenols with Nonalkyl Substituents. Phenols with nonalkyl aromatic substituents have hydroxyl proton chemical shifts in a broader chemical shift range t h a n t h a t observed for the alkyl phenols (see Tables 11, 111, IV). This is not unexpected because these substituents introduce a large electronic effect not present in the alkyl phenols. Electron withdrawing groups increase the positive nature of the hydroxyl oxygen and cause a weakening of the oxygen-hydrogen bond. A bond
I
I
I
I
I
I
-1.0
.8
.6
A
.2
0
0-
I
I
I
I
.2
.4
.6
.E
Figure 5. Correlation of NMR chemical shift of with u (Hammett’s constant)
I 1.0
phenolic hydroxyl
Phenol
+ meta-substituted
0 para-substituted A poly-substituted
elongation or weakening can be expected to cause a low field shift of the hydroxyl proton signal (17). This effect is clearly indicated in the reported data. The effect of electron donating substituents is less clear. Shifts to both high and low field, with respect to phenol per se, are observed. Because the hydroxyl group acts as an electron donating group, this variation presumably arises from the complex electronic interactions obtained when two such groups are present on an aromatic ring. A more difficult analysis to determine the electron densities at each ring position may be necessary to explain the direction of the shift obtained with a particular electron donating substituent. Several workers have reported correlations of NMR chemical shifts with substituent constants, such as Hammett’s constant. Among these, Klinck and Stothers (6) report a rough correlation of the chemical shift of the formyl proton in substituted benzaldehydes with Hammett’s u. Paterson and Tipman (11) report a rough correlation between internal ortho- ring proton shift and u in substituted phenols. These authors, however, report that a correlation of the infinite dilution hydroxyl proton chemical shift with u in this system is unjustified due to the small range of the values obtained in a given solvent. Ouellette (10) obtained a good correlation between the hydroxyl proton chemical shift of substituted phenols in dimethyl sulfoxide and Hammett’s u-. I n dimethyl sulfoxide and in HMPA, specific hydrogen bonded solventphenol species are expected to exist. This is supported by the absence of a dependence of the chemical shift on concentration in both solvents. Also, a
constant difference between the chemical shift of a particular phenol in HMPA and in dimethyl sulfoxide was observed, suggesting the existence of similar hydrogen bonded species. The occurrence of the chemical shift at ca. 1.0 p.p.m. lower field in HMPA indicates a stronger solvent-phenol hydrogen bond in this solvent (IS). Under these conditions, a dependence of hydroxyl chemical shift on u can be expected. The correlation between the hydroxyl proton chemical shift and u for phenol and 18 meta- and para-substituted phenols is shown in Figure 5. Because of the small differences among u’s for alkyl substituents, 4-methylphenol was chosen as being representative of the alkyl phenols. 4-Phenoxyphenol is not included in this correlation because significant differences exist in the value reported for u of this compound (5, 9). A linear relation between the chemical shift and u is obtained. Only four of the twenty examples reported have chemical shifts which differ by more than 10 C.P.S. from the values predicted assuming a linear dependence. These deviations are observed for 3-methoxyphenol, 4-phenylphenol, 4-formylphenol, and 4acetylphenol. Deviations in the latter two cases are not unexpected. Discrepancies have been reported when attempting to correlate u with ionization constants of para-substituted phenols which contain strongly electron withdrawing groups on the aromatic ring (such as formyl or acetyl). Hammett (2) proposed a modlfied substituent constant u- for these cases. The use of ~ ( 6 for ) 4-formyl and 4-acetylphenol gave points which showed large deviations from the linear plot in the opposite direction from those indicated VOL 38, NO. 1 1 , OCTOBER 1966
1483
The use of Figure 6 in identifying unknown o r b s u b s t i t u t e d phenols appears limited since few values for U* are available. Also, the assumed linear dependence of the hydroxyl chemical shift on U * is questionable. An attempt to extend this correlation to polysubstituted phenols with both ortho and meta or para substituents proved unsuccessful. No relation was observed between the h e a r sum u U* and the hydroxyl chemical shift (examples from Table IV) , Additional data will be needed before the feasibility of this procedure can be determined. Interferences. Materials having protons with chemical shifts greater than 8 p.p.m., such as aldehydes, can interfere with the identification of components in phenol mixtures. These materials can often be identified by comparison of the N M R spectra in H M P A and chloroform-d. Materials containing exchangeable protons can also prevent the identification of phenols. A low level of water causes broadening of the phenolic hydroxyl peak. Low levels of more acidic materials, however, can lead to appreciable changes in the phenolic hydroxyl chemical shift.
+
I
-1.0
I
I
I
.e
.6
.4
I
I
I
I
I
0
.2
.4
.6
.8
I
.e
I til)
Q*
Figure 6. Correlation of NMR chemical shift of phenolic hydroxyl with u* (Taft’s constant)
-I- Phenol 2-Methylphenol
0 2-Methoxyphenol 0 2-Ethoxyphenol
A 2-Bromophenol U 240dophen0l
_* 2-Nitrophenol
A 0
2,6-Dimethylphenol 2,6-Dimethoxyphenol
for u. Three points for polysubstituted phenols are included in Figure 5 (3,4dimethylphenol, 3,5-dimethylphenolI and 4-chloro-3,5-dimethylphenol). All fall within 10 C.P.S. of the chemical shift value predicted using the sum of the Hammett’s constants of the substituents. A value of p can be determined from the slope of this plot. The value of 1.83 obtained is higher than the value of 1.29 obtained by Ouellette (10) and is close to the value of 2.11 reported for the dissociation of phenols (1).
Figure 5 can prove useful in identifying an unknown phenol or components in mixtures of phenols. The plot makes it possible to use the hydroxyl chemical shift t o estimate u for the substituent. A table of Hammett’s constants can then be used to identify possible substituents. Ortho-substituted phenols, of course, cannot be identified in this way. As was observed for the alkylphenols, quantitative ortho/meta/para isomer analysis is possible in some cases. Two of the five ortho/metu/para systems reported in Table 111can be analyzed by hydroxyl peak area measurement and two cannot. The fifth system, the formyl phenols, also gives unresolved hydroxyl peaks. This system, however, gives fully resolved formyl proton peaks, permitting analysis from area measurements of these peaks. Figure 5 can be used to predict the potential of this procedure for analysis of a given metupara isomeric mixture. Assuming a
1484
ANALYTICAL CHEMISTRY
deviation of 10 C.P.S. in the hydroxyl chemical shift and a line width of 2.0 C.P.S., analysis should prove possible if u meta and u para differ by ca. 0.1. Analysis of mixtures of polysubstituted phenols may also be possible if the sum of the Hammett’s constants differ by ca. 0.1. Because the hydroxyl chemical shifts of ortho-substituted phenols will be affected by both steric and electronic factors, less satisfactory correlations with ortho substituent constants can be expected. Figure 6 gives such a correlation using Taft’s constant U* (14). Data from Tables I1 and 111 are included for phenol and six mono-orthosubstituted phenols. Although considerable scatter is observed, a trend for increasing chemical shift with increasing U * is evident. Assuming a linear relation, five of the seven chemical shifts are within 10 C.P.S. of their predicted values. The remaining two points are within 20 C.P.S. of the value predicted. Two points are included for di-orthosubstituted phenols using the sum of the Taft’s constants of the substituents. One of these points gives excellent agreement while the other differs by more than 40 C.P.S. It is interesting to note, however, that, even with the uncertainty of the linear dependence of the hydroxyl chemical shift on u*, the slope of this curve gives a value for p of 2.0. This value is close to the value of p determined by Figure 5 and to the value reported for the ionization of phenols.
LITERATURE CITED
(1) Bunnett,
J. F., in “Investigation of Rates and Mechanisms of Reactions,” Part I, S. L. Friess, E. S. Lewis, A. Weissberger, eds., p. 216, Interscience, New York, 1961.
(2) Ibid., .218. (3) Crutcl%eld, M. M., Irani, R. R.,
Yoder, J. T., J. Am. Oil Chemists’
SOC. 41, 129 (1964). (4) Freedman, R. W., Croitoru, P. P., ANAL.CHEM.36, 1389 (1964). (5) Jaffe, H. H., Chem. Rev. 53,191 (1953). (6) Klinck, R. E., Stothers, J. B., Can. J . Chem. 40, 1071 (1962). (7) Langer, S. H., Pantages, P., Wender, I., Chem. Znd. (London)1958, 1664. (8) Lindeman, L. P., Nicksi, S. W., ANAL. CHEM.36, 2414 (1964). (9) McDaniel, D. H., Brown, H. C., J. Org.Chem. 23, 420 (1958). (10) Ouellette, R. J., Can. J . Chem. 43, 707 (1965). (11) Paterson, W. G., Tipman, N. R., Zbid., 40, 1071 (1962). (12) Puttnam, N. A., J . Chem. SOC.1960, 486. (13) Somers, B. G., Gutowsky, H. S., J. Am. Chem. SOC.85, 3065 (1963). (14) Taft, R. W., Jr., Zbid., 75, 4231 (1953). (15) Vine ard, B. D., Godt, H. C., Jr., hem. 3, 1144 (1964). (1li”;B. amaguchi, I., Bull. Chem. SOC. Japan 34, 451 (1961). (17) Yoshida, Z., Haruta, M., Tetrahedron Lellers 42, 3745 (1965). (18) Young, C. W., DuVall, R. B., Wright, N., ANAL. CHEM. 23, 709 (1951).
c’
RECEIVEDfor review August 1, 1966. Accepted August 15, 1966.
