Replacement of an alkyl group in dialkyl ethers by an aromatic substituent deshields the ether oxygen, as expected, due to delocalization of 1r-electron density from oxygen into the aromatic ring. In going from dimethyl ether to anisole, a 102 ppm downfield shift is observed. 26 By studying the electronic effects of substituents on 170 shifts of p-substituted anisoles, Iwamura et al. 26 have shown that the no shieldings in these compounds are dominated by the electron density on the oxygen atom, which affects its 2p orbital size, {c3) 2P term in Equation 1. The importance of the interaction of p-electrons of the ether oxygen with the aromatic 1r-system in determining the no shifts of alkyl phenyl ethers was
demonstrated by Kalabin and co-workers.27 These authors observed that the first two sub
stitutions of the alkyl protons in anisole by methyl groups gave the expected downfteld shifts due to J3-CH3 effects, 29 and 25 ppm, respectively (Table 42). However, the third methyl substitution produced no change in the 170 shielding. Kalabin et ai.27 explained the origin of this effect as the increased localization of charge density on the ether oxygen in 323, compared to 322 and 321. Sterle inhibition of coplanarity of the oxygen atom with the aromatic ring in 323, caused by the bulky t-butyl group, produces a loss in p-'TT-interactions and an increase in the electronic charge on oxygen. By subtracting out the contribution of the alkyl groups (Salkyi• see footnote b in Table 42) in 321 to 323 from their 170 chemical shifts, Kalabin and co-workers27 showed that the resultant 170 shifts, which should be a measure of p-11"-interactions, are practically the same for anisole, phenetole (321), and phenyl isopropyl ether (322). However, this 170 shift for phenyl t-butyl ether (323) is 10 ppm upfteld of anisole, suggesting increased electron density on the oxygen atom or a change in the conformation of p-orbitals.
TABLE 42
170 NMR Chemical Shifts of Aromatic Ethers
No. Compound o.,oã P-SCS(CH,)' &alkyl b &corrKtedc
86 C,H,OCH, 49
321 C,H,OCH,CH, 78 29 29 49
322 C,H,OCH(CH3), 103 25 51 52
323 C,H,OC(CH,), 103 25 63 39
Taken from Reference 27.
• Contribution to ll110 by alkyl groups (Et, i-Pr, t-Bu) calculated from the shift for ethyl alkyl ether minus the shift for ethyl methyl ether. Chemical shifts were taken from Reference II .
c &170 minus &alkyl
The response of the 170 chemical shift of an aromatic ether oxygen to steric effects from substituents in the aromatic ring was clearly demonstrated in a study of ortho-substituted anisoles68 (Scheme 30). While mono ortho substitution by alkyl groups provide negligible effects, even with the bulky t-butyl group, di-ortho substitution results in substantial upfield shifts of the 170 resonances in 325 and 327 (38 and 21 ppm, respectively). Sterle hindrance
48.0 ppm 46.2 ppm 16.5 ppm
OCH3 OCH3
0 ac•, H0C'(yCHo
86 324 325
48.0 ppm 48.8 ppm 27.3 ppm
OCH3 OCH3
0 6C(CHoh (HoChC'(yC(CHoh
86 326 327
SCHEME 30
190 170 NMR Spectroscopy in Organic Chemistry
from the two ortho substituents for resonance interactions of the oxygen with the aromatic
'TT system leading to increased electron density (decreased (r-3) 2P term in Equation 1) has been suggested as the cause of the shielding effect. 68 However, this effect becomes smaller for the bulkier t-butyl substituent, 21 ppm in 327 as opposed to 32 ppm in 325,68 Scheme 30. Additional examples are shown in Scheme 31. As the size of the ortho alkyl substituents
16.5 ppm OCH3
16.7 ppm OCH3
13.5 ppm OCH3 H3C'OCH3
~I HsCz'OCzHs
~I <cH3>zHc'OcH<cH3lz
~I
~ ~
~
325 328 329
27.0 ppm 24.3 ppm
OCH3 OCH3
H3CDC(CH3)3 CH3*C(CH3)3
~I ~I
~ ~
327 330
CH3 331 SCHEME 31
is increased from CH3 , C2H5 to i-Pr, shielding of the ether oxygen increases, but with two bulky tert-butyl groups, shielding decreases. This effect persists for cases (330 and 331) in which at least one of the two substituents is a large group. Repulsive van der Waals interactions between the substituents and the methoxy group have been invoked to explain the decrease in the upfield effect for the 170 shifts in 327, 330, and 331.68 By examining the orientation of the methoxy group in analogous 2,6-dialkylanisic acids (331a to f, Scheme 32) from their X-ray crystal structures, Schuster et al.69 arrived at a similar conclusion. The authors suggested that in sterically congested anisoles, the nonbonded interactions between the methoxy oxygen lone pairs of electrons and the C-H bonds of the ortho substituents should localize electron density in the plane containing the oxygen, ipso, and para carbon atoms, thereby rendering the electron delocalization into the aromatic ring more feasible.
331a X= Y = H 331b X= Y = CH3 331c X= Y = CzHs 331d X = Y = IãC3H7 331e X = Y = tãC4H9
3311 X = tãC4H9 ; Y: H SCHEME 32
In contrast to the effect produced by an ortho alkyl substituent, an ortho methoxy group induces a dramatic shielding of the aromatic ether oxygen (15 ppm) in 1 ,2-dimethoxybenzene (332) (Scheme 33). Wysocki et al68 proposed that the placement of the methoxy group out
33.5 ppm 10.5 ppm 9.4 ppm
OCH3 35.8 ppm OCH3
36.4 p D m OCH3