Conformational Studies by Dynamic NMR
J . Org. Chem., Vol. 62, No. 22, 1997 7595
that can be derived from the spectra in the solid thus
match quite well the MM predictions of a preferred
racemic conformation for derivatives 2-4.
Exp er im en ta l Section
Ma ter ia l. Compounds 1 and 2 were commercially available
whereas 3 and 4 were synthesized using the same procedure.
As an example the synthesis of 3 is reported in detail.
1-[2-(1-Hyd r oxyp r op yl)p h en yl]p r op a n -1-ol (3′). To a
solution of 40 mL (40 mmol) of 1 M EtMgBr in 10 mL of dry
THF kept at -35 °C under N2 was added dropwise a solution
of 2.4 g (18.2 mmol) of phthalic aldehyde in 5 mL of dry THF.
After 20 min the temperature was raised to 20 °C and the
reaction quenched with a saturated solution of NH4Cl in water.
The organic layer was separated, washed with water (4 × 20
mL), and dried (Na2SO4), and subsequently the solvent was
removed by distillation at reduced pressure. The crude
product (1.8 g) was purified by chromatography on silica gel
(eluent ether:petroleum ether 2:1) to yield 0.5 g of a pale yellow
oil: 1H NMR (CDCl3) δ 0.97 (t, 3 H, Me), 2.80 (m, 2 H, CH2),
2.29 (s, 1H, OH), 4.88 (dd, 1 H, CH), 7.27 (m, 1H, Ar); 7.42
(m, 1H, Ar); 13C NMR (CDCl3) δ10.7 (Me), 31.4 (CH2), 72.4
(CH), 126.3 (CH,Ar), 127.7 (CH,Ar), 141.4 (quat, Ar). Anal.
Calcd for C12H18O2: C, 74.19; H, 9.34. Found: C, 74.08; H,
9.28.
1-(2-P r op ion ylp h en yl)p r op a n -1-on e (3). To a mixture,
kept under nitrogen, of 3′ (0.3 g, 1.5 mmol in 5 mL of dry
benzene) and of RuCl2(PPh)328 (173 mg, 0.18 mmol) was slowly
(1 h) added a solution of t-BuOOH (0.54 g, 6 mmol in 5 mL of
dry benzene). After an additional hour of stirring, the reaction
was quenched by adding black Pd powder. The solid was
filtered off and the filtrate concentrated under reduced pres-
sure. The residue was purified by chromatography on a
preparative SiO2 TLC (eluent ether:petroleum ether 2:1) to
obtain a pale yellow oil (0.2 g): 1H NMR (CDCl3) δ 1.22 (t, 3
H, Me), 2.85 (q, 2 H, CH2), 7.55(s, 2H, Ar); 13C NMR (CDCl3)
δ 8.2 (Me), 34.4 (CH2), 127.5 (CH,Ar), 130.8 (CH,Ar), 139.2
(quat, Ar), 204.6 (quat, CO). Anal. Calcd for C12H14O2: C,
75.76; H, 7.42. Found: C, 75.80, H, 7.50.
F igu r e 3. 13C spectrum (75.5 MHz) of 2 at -140 °C in a Me2O
solution (top): underneath is displayed the solid state (CP-
MAS) spectrum at room temperature, also at 75.5 MHz.
a pair of enantiotopic carbons not related by a plane (or
center) of symmetry usually display, in the crystal, two
different NMR peaks. If such a plane (or center) of
symmetry is present the same multiplicity of the solution
spectrum (i.e. a unique peak for both such carbons) is
maintained in the solid state.12,24,25 As a consequence we
expect that in a 13C CP-MAS spectrum the meso con-
former would yield a single peak whereas the racemic
conformer would yield two different peaks for each pair
of carbons. The latter was indeed the case observed in 2
where the ten carbons yield five pairs of 1:1 doublet
signals26,27 (Figure 3). An analogous result was obtained
for 3 (R ) Et), whose solid state spectrum had to be
obtained, however, at -70 °C since this compound does
not crystallize at room temperature. The conclusions
1-(2-Isobu tyr ylp h en yl)-2-m eth ylp r op a n -1-on e (4): 1H
NMR (CDCl3) δ 1.20 (d, 6 H, Me), 3.18 (m, 1 H, CH), 7.55 (m,
2H, Ar); 13C NMR (CDCl3) δ 18.7 (Me), 38.3 (CH), 127.9 (CH,
Ar), 130.6 (CH, Ar), 139.4 (quat, Ar), 208.1 (quat, CO). Anal.
Calcd for C14H18O2: C, 77.03; H,8.31. Found: C, 77.09; H,
8.35.
NMR Sp ectr a . The low-temperature solution spectra of
compounds 1-3 were run at 300 MHz (1H) or 75.5 MHz (13C);
the 13C spectrum of 4 was recorded at 100.6 MHz. The samples
were prepared by condensing the gaseous solvents (CHF2Cl,
Me2O), by means of liquid nitrogen, into NMR tubes (contain-
ing the desired products with a small amount of CD2Cl2 for
the lock operation) connected to a vacuum line. The samples
were then sealed under vacuum and introduced into the
precooled probe of the spectrometer. The line shape analysis
was performed by means of computer programs based on the
Bloch equations.29 At temperatures lower than -162 °C
compound 1 is almost insoluble in CHF2Cl thus, in order to
have an approximate value of the line width in absence of
exchange for the computer simulation, the following criterion
was adopted.30 At temperatures where the Ar-CHO rotation
is still rapid, so that the HCO signal is not yet exchange
broadened (i.e., -120, -130 °C), the ratio between its line
width and that of CHF2Cl was determined (about 1.5). On
the assumption that this ratio remains essentially constant
on further lowering the temperature, the line width of CHF2Cl,
measured at -162 °C (43 Hz), was multiplied by such a factor,
therefore assigning a 65 Hz intrinsic line width to the HCO
signals of 1 at that temperature. We also checked that
uncertainties as large as 50% on this line width only affect
the resulting ∆Gq value by 0.1 kcal mol-1. The 13C-NMR solid
(24) Casarini, D.; Lunazzi, L.; Macciantelli, D. J . Org. Chem. 1988,
53, 177.
(25) We stress that such a statement is not wholly unambiguous
since it is possible to find, occasionally, molecules with a plane of
symmetry that have their NMR lines split in the solid state in that
the molecular symmetry might not be coincident with the site sym-
metry (for further details see ref 24 and references cited therein).
(26) On the contrary the solid state spectrum of the isomeric 1,4-
diacetylbenzene displayed a single line for the CH3 carbons, as expected
for a structure retaining, in the crystal, a molecular plane of symmetry
(Lipmaa, E. T.; Alla, M. A.; Pehk, K. T.; Engelhardt, G. J . Am. Chem.
Soc. 1978, 100, 1929. See also: Penner, G. H.; Wasylishen, R. E. Can.
J . Chem. 1989, 67, 525).
(27) The cause underlying the splitting of the CO signal observed
in the solid state spectrum of 1 is different from that of 2 and 3. In 1
it is a consequence of the syn-anti relationship of the HCO groups in
the 1-ZE conformation and corresponds to the same situation detected
in solution (see Figure 1). In 2, on the other hand, it is due to the
properties of an asymmetric molecule in the crystal and cannot be
detected in the solution spectra. Such a difference is clearly reflected
in the amount of the splitting which is quite small (1.8 ppm) in 1 but,
for instance, much larger (6.5 ppm) in 2. Likewise the separation of
the ring carbon signals is so small as to be almost undetectable in 1
but, again, large in 2 (3.4-8.3 ppm).
(29) Sandstro¨m, J . Dynamic NMR Spectroscopy; Academic Press:
London, 1982.
(30) Lunazzi, L.; Macciantelli, D.; Bernardi, F.; Ingold, K. U. J . Am.
Chem. Soc. 1977, 99, 4573.
(28) Murahashi, S.-I.; Naota, T. Synthesis 1993, 433.