Correct values of the rotation barriers of 1,8-ditolylanthracenes

Article abstract of DOI:10.1021/jo070679q

(Chemical Equation Presented) The rotation barriers of two 1,8-ditolylanthracene derivatives have been measured by accurate line-shape simulation of their variable-temperature NMR spectra. Both values were found to be more than twice as large as those pre

Full text of DOI:10.1021/jo070679q

Correct Values of the Rotation Barriers of
1,8-Ditolylanthracenes
Lodovico Lunazzi, Michele Mancinelli,1 and
Andrea Mazzanti*
Department of Organic Chemistry “A. Mangini”, UniVersity of
Bologna, Viale Risorgimento, 4 Bologna 40136, Italy
mazzand@ms.fci.unibo.it
ReceiVed April 3, 2007
The rotation barriers of two 1,8-ditolylanthracene derivatives
have been measured by accurate line-shape simulation of
their variable-temperature NMR spectra. Both values were
found to be more than twice as large as those previously
reported in the literature.
FIGURE 1. Energy surface (E in kcal mol-1) and rotation pathways
computed4 as a function of the two torsion angles (æ) about the tolyl-
anthracene bonds of derivative 1. The solid and open dots represent
the trans and cis conformer, respectively.
Some time ago House and co-workers2 measured, by variable-
temperature NMR spectroscopy, the rotation barriers of 1,8-
diarylanthracene derivatives. The values, reported as activation
energies derived from the Arrhenius equation, were unusually
low with respect to the expectation for this type of compound,
e.g., 5.3 and 10.4 kcal mol-1 for compounds 1 and 2,
respectively (Chart 1). The authors themselves were surprised
by such incredibly low values and a few years later published
a paper3 where a possible explanation was proposed.
CHART 1
The energy surface of compound 1, computed4 as a function
of the anthracene-tolyl torsion angle æ (Figure 1), shows that
the rotation pathways interconverting the trans and cis conform-
ers (indicated by red lines) run parallel to the respective axes,
indicating that the two motions are independent of each other
and the processes, accordingly, are not correlated.5 The rotation
SCHEME 1. Ab Initio Computed Structures of the Trans
and Cis Conformers of 1a
barrier is calculated to be much larger (about 16 kcal mol-1
)
than the reported2 value. Such a theoretical value was refined
using the more reliable ab initio approach6 that likewise
(1) In partial fulfillment for receiving a Ph.D. degree in Chemical
Sciences, University of Bologna
(2) House, H. O.; Hrabie, J. A.; VanDerveer, D. J. Org. Chem. 1986,
51, 921.
(3) House, H. O.; Holt, J. T.; VanDerveer, D. J. Org. Chem. 1993, 58,
7516.
(4) Molecular Mechanics approach using the MMFF force field as in
PC Model v 7.5, Serena Software, Bloomington, IN.
(5) (a) Casarini, D.; Grilli, S.; Lunazzi, L.; Mazzanti, A. J. Org. Chem.
2001, 66, 2757. (b) Grilli, S.; Lunazzi, L.; Mazzanti, A. J. Org. Chem.
2001, 66, 4444. (c) Grilli, S.; Lunazzi, L.; Mazzanti, A. J. Org. Chem.
2001, 66, 5853. (d) Jog, P. V.; Brown, R. E.; Bates, D. K. J. Org. Chem.
2003, 68, 8240. (e) Casarini, D.; Lunazzi, L.; Mazzanti, A.; Mercandelli,
P.; Sironi, A. J. Org. Chem. 2004, 69, 821.
a The relative energies (E) are in kcal mol-1. Methyl groups are shown
in red for convenience). The small amplitude torsion (libration) of the tolyl
ring about the orthogonal situation has a very small barrier (less than 1
kcal mol-1), so that in the NMR timescale the trans form displays dynamic
C2 (chiral) and the cis form dynamic Cs (achiral) symmetry.
indicated the trans form to be more stable than the cis form (by
0.2 kcal mol-1 as in Scheme 1) and predicted again the existence
of a sp2-sp2 rotation barrier (12.2 kcal mol-1) still significantly
larger than the 5.3 kcal mol-1 value from the literature.2 A
similar value had been also calculated7 (12.9 kcal mol-1) for
(6) Frisch, M. J., et al. Gaussian 03, Revision D.01; Gaussian, Inc.:
Wallingford, CT, 2004 (See Supporting Information).
10.1021/jo070679q CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/13/2007
J. Org. Chem. 2007, 72, 5391-5394
5391

TABLE 1. Experimental Activation Parameters for Compounds 1
a
and 2 (∆Gq, ∆Hq, Ea in kcal mol-1, ∆Sq in cal mol-1 T-1
)
compound
∆Gq
11.22 (0.02) 11.45 (0.2)
21.30 (0.03) 21.0 (0.3) -0.75 (1.0) 21.8 (0.3) 13.2 (0.2)
∆Hq
∆Sq
Ea
log A
1
2
1.1 (1.0) 11.9 (0.2) 13.3 (0.2)
a The value in parentheses is the estimated uncertainty.
(right). Also, the aromatic hydrogen in position 9 yields two
signals with the same 63:37 ratio, and these were likewise
simulated at the same temperatures where the methyl lines had
been examined. Equal values for the rate constants were obtained
in both cases, thus providing an independent check of the
accuracy of the present data. The 10 rate constants obtained in
this way (Table S-1 of Supporting Information) allowed us to
derive the activation parameters using both the Eyring and the
Arrhenius equations. The corresponding data are collected in
Table 1, and as often observed in the dynamics of conforma-
tional processes, the ∆Sq value is negligible9 within the
experimental uncertainty. From our experiment it is quite evident
that the interconversion barrier, indicated either as ∆Gq, ∆Hq,
or Ea, is in good agreement with the ab initio calculations10 but
more than twice as large as the 5.3 kcal mol-1 value of the
previous experiments.2
Distinguishable NMR methyl signals for the cis and trans
conformers of 2 are observed at ambient temperature, the upfield
signal displaying a slightly higher intensity, i.e., 54% in CDCl3
and 53% in dimethylformamide-d7 (DMF-d7). Ab initio calcula-
tions6 indicate that the cis form has an energy 0.25 kcal mol-1
higher than the trans form (Supporting Information), suggesting
again that the latter should be the more stable conformer. It
should be pointed out, however, that the relative proportions of
the trans and cis conformers are nearly equal in this case, thus
making an assignment based solely on theoretical considerations
less reliable. For this reason we also obtained the support of an
experimental determination.
FIGURE 2. (Left) 1H NMR methyl signals of compound 1 (600 MHz
in CD2Cl2) as a function of temperature. (Right) Line-shape simulation
obtained with the rate constants indicated.
Following the procedure reported11 for the assignment of
symmetric isomers, the 13C satellite spectra of the methyl signals
the sp2-sp3 rotation barrier in an anthracene substituted by two
CF3CHOH groups in positions 1 and 8, although in that case
an experimental determination to confirm the theoretical predic-
tion had not been provided.
(8) PC version of the DNMR program no. 633, QCPE, Indiana
University, Bloomington, IN.
Also, the ab initio computed6 barrier of 2 (20.8 kcal mol-1
)
(9) Dondoni, A.; Lunazzi, L.; Giorgianni, P.; Macciantelli, D. J. Org.
Chem. 1975, 20, 2979. Hoogosian, D. S.; Bushweller, C. H.; Anderson,
W. G.; Kigsley, G. J. Phys. Chem. 1976, 80, 643. Lunazzi, L.; Cerioni, G.;
Ingold, K. U. J. Am. Chem. Soc. 1976, 98, 7484. Lunazzi, L.; Dondoni, A.;
Barbaro, G.; Macciantelli, D. Tetrahedron Lett. 1977, 18, 1079. Forlani,
L.; Lunazzi L.; Medici, A. Tetrahedron Lett. 1977, 18, 4525. Bernardi, F.;
Lunazzi, L.; Zanirato, P.; Cerioni, G. Tetrahedron, 1977, 33, 1337. Lunazzi,
L.; Magagnoli, C.; Guerra, M.; Macciantelli, D. Tetrahedron Lett. 1979,
3031. Cremonini, M. A.; Lunazzi, L.; Placucci, G.; Okazaki, R.; Yamamoto,
G. J. Am. Chem. Soc. 1990, 112, 2915. Anderson, J. E.; Tocher, D. A.;
Casarini, D.; Lunazzi, L. J. Org. Chem. 1991, 56, 1731. Borghi, R.; Lunazzi,
L.; Placucci, G.; Cerioni, G.; Foresti, E.; Plumitallo, A. J. Org. Chem. 1997,
62, 4924. Garcia, M. B.; Grilli, S.; Lunazzi, L.; Mazzanti, A.; Orelli, L. R.
J. Org. Chem. 2001, 66, 6679. Garcia, M. B.; Grilli, S.; Lunazzi, L.;
Mazzanti, A.; Orelli, L. R. Eur. J. Org. Chem. 2002, 4018. Casarini, D.;
Rosini, C.; Grilli, S; Lunazzi, L.; Mazzanti, A. J. Org. Chem. 2003, 68,
1815. Casarini, D.; Grilli, S.; Lunazzi, L.; Mazzanti, A. J. Org. Chem. 2004,
69, 345. Bartoli, G.; Lunazzi, L.; Massacesi, M.; Mazzanti, A. J. Org. Chem.
2004, 69, 821. Casarini, D.; Coluccini, C.; Lunazzi, L.; Mazzanti, A.;
Rompietti, R. J. Org. Chem. 2004, 69, 5746.
(10) Since the trans to cis conversion can be accomplished by rotation
of either of the two tolyl rings, the rotation rate of a single ring corresponds
to one-half of the measured rate constants. The corresponding ∆Gq, ∆Hq,
and Ea thus become, in this case, 0.3 kcal mol-1 higher (i.e. 11.5, 11.8, and
12.2 kcal mol-1, respectively), and it is these values that, in principle, should
be compared to the theoretical rotation barrier of 12.2 kcal mol-1 (see
Lunazzi, L.; Mazzanti, A.; Minzoni, M. J. Org. Chem. 2007, 72, 2501).
(11) Lunazzi, L.; Mazzanti, A. J. Am. Chem. Soc. 2004, 126, 12157.
turned out to be much higher than 10.4 kcal mol-1 2,3
.
Since the
values derived from these calculations are seemingly at variance
with the experimental data, we performed an accurate verifica-
tion of the previous experiments by taking advantage of better
instrumentation than available in the past. Compounds 1 and 2
were selected for this purpose because determinations of the
corresponding barriers could be carried out in both the low
temperature (compound 1) and the high-temperature (compound
2) range.
As shown in Figure 2 (left) the 1H NMR spectrum of 1 (600
MHz in CD2Cl2) at -77 °C displays two methyl signals with
different intensities, the ratio being 63:37. The more intense
downfield signal was assigned to the chiral trans conformer,
following the prediction of the above-mentioned ab initio
computations (Scheme 1).
The computer line-shape simulation8 of these lines was
performed at 10 significant temperatures in the range -66 to
-45 °C: a few selected sample traces are reported in Figure 2
(7) Pe´rez-Trujillo, M.; Maestre, I.; Jaime, C.; Alvarez-Larena, A.; Pinella,
J. F.; Virgili, A. Tetrahedron: Asymmetry 2005, 16, 3084.
5392 J. Org. Chem., Vol. 72, No. 14, 2007

FIGURE 3. (a) Methyl signals (1H, 600 MHz) of 2 in CDCl3 at 0
°C13 displaying in the inset the 13C satellite signals. (b) Spectrum
obtained by irradiating the satellites of the downfield line. (c) Spectrum
obtained by irradiating the satellites of the upfield line.
of each of the two conformers were irradiated using the
DPFGSE-NOE sequence.12 As shown in Figure 3 (trace b),
irradiation of the satellites of the less intense low-field signal
yields a substantial NOE effect, indicating that this signal
corresponds to the cis conformer, where the hydrogens of the
two methyl groups are sufficiently close (computed average
distance 4.60 Å) as to experience a reciprocal NOE enhance-
ment. On the other hand, irradiation of the satellites of the more
intense upfield signal (trace c) does not produce any NOE effect,
indicating that this corresponds to the trans conformer, where
the hydrogens of the two methyl groups are too far apart
(computed average distance 6.94 Å) to experience the reciprocal
NOE enhancement. These experimental results confirm, there-
fore, the theoretical assignment.
FIGURE 4. (Left) 1H NMR methyl signals of compound 2 (600 MHz
in DMF-d7) as a function of temperature. (Right) Line-shape simulation
obtained with the rate constants indicated.
substituent of analogous size in the ortho position15 and that of
2 lies in the same range as that of biphenyls bearing two
substituents of analogous size in the ortho, ortho′ positions.16
Experimental Section
As shown in Figure 4 (left) the two methyl signals of 2
broaden on raising the temperature (in DMF-d7 as solvent),
eventually coalescing into a single line. Line-shape simulation
(Figure 4, right) provides the corresponding rate constants for
the trans to cis interconversion. Twelve such rates were
determined in the range from 104 to 136 °C (Table S-2 of
Supporting Information), and from these values the activation
parameters collected in Table 1 were obtained.14 In this case
the experimental barrier also agrees well with that predicted by
the ab initio computations and is at least twice as large as the
10.4 kcal mol-1 previously reported.2,3
It is therefore demonstrated that the unusually low values
quoted for the barriers of 1 and 2 were the consequence of
measurements of insufficient accuracy, so that it is not necessary
to propose any explanation to justify barriers that actually are
in keeping with the expectations. For instance, the barrier of 1
lies in the same range as that of biphenyls bearing a single
Materials. 1,8-Dibromoanthracene7 was prepared according to
the literature; o- and m-tolylboronic acids were commercially
available as well as the Pd(PPh3)4 catalyst.
1,8-Di-m-tolylanthracene (1).2 To a solution of 1,8-dibromo-
anthracene (0.336 g, 1 mmol in 6 mL of benzene), K2CO3 (2 M
solution, 1.25 mL), m-tolylboronic acid (0.340 g, 2.5 mmol,
suspension in 6 mL of ethanol), and Pd(PPh3)4 (0.231 g, 0.2 mmol)
were added at room temperature. The stirred solution was refluxed
for 2-3 h, the reaction being monitored by GC-MS. After the first
coupling was complete, a second amount of m-tolylboronic acid
(0.340 g, 2.5 mmol, suspension in 6 mL of ethanol) and Pd(PPh3)4
(0.231 g, 0.2 mmol) were added at room temperature, and the
solution was refluxed again for 3 h. Then CHCl3 and H2O were
added, and the extracted organic layer was dried (Na2SO4) and
evaporated. The crude product was prepurified by chromatography
on silica gel (hexane/Et2O 50:1) to yield 0.28 g of a mixture
containing mainly 1-bromo-8-m-tolylanthracene, 1-m-tolyl-
anthracene, and compound 1. Analytically pure samples of 1 were
obtained by semipreparative HPLC on a Luna C18(2) column (5
µm, 250 × 10 mm, 4 mL/min, ACN/H2O 90:10 v:v).
(12) (a) Stonehouse, J.; Adell, P.; Keeler, J.; Shaka, A. J. J. Am. Chem.
Soc. 1994, 116, 6037. (b) Stott, K.; Stonehouse, J.; Keeler, J.; Hwang, T.
L.; Shaka, A. J. J. Am. Chem. Soc. 1995, 117, 4199. (c) Stott, K.; Keeler,
J.; Van, Q. N.; Shaka, A. J. J. Magn. Reson. 1997, 125, 302. (d) Van, Q.
N.; Smith, E. M.; Shaka, A. J. J. Magn. Reson. 1999, 141, 191.
(13) The NOE experiment was carried out at 0 °C to avoid the possibility
of a saturation transfer process between the two conformers.
(15) Lunazzi, L.; Mazzanti, A.; Minzoni, M.; Anderson, J. E. Org. Letters
2005, 7, 1291. Mazzanti, A.; Lunazzi, L.; Minzoni, M.; Anderson, J. E. J.
Org. Chem. 2006, 71, 5474. Lunazzi, L.; Mazzanti, A.; Minzoni, M. J.
Org. Chem. 2006, 71, 9297.
(14) As discussed in ref 10, rotation of a single tolyl group of 2 has, in
(16) Bott, G.; Field, L. D.; Sternhell, S. J. Am. Chem. Soc. 1980, 102,
5618.
this case, an activation parameter 0.5 kcal mol-1 higher.
J. Org. Chem, Vol. 72, No. 14, 2007 5393

1,8-Di-o-tolylanthracene (2)2 was prepared using the same
procedure of 1 and o-tolylboronic acid.
shaped pulse was calculated with a refocusing-SNOB shape20 and
a pulse width of 185 ms.
NMR Spectroscopy. The spectra were recorded at 600 MHz
for 1H and 150.8 MHz for 13C. The assignments of the 13C signals
were obtained by two-dimensional experiments (edited-gHSQC17
and gHMBC18 sequences). Temperature calibrations were performed
immediately before the experiments using a Cu/Ni thermocouple
immersed in the same solvents used for the measurements (CH2-
Cl2 and DMF) contained in a nonspinning dummy sample tube and
under conditions as nearly identical as possible. The uncertainty in
the temperatures was estimated from the calibration curve to be
(0.5 °C. Line-shape simulations8 were performed by taking into
account the chemical shift variation as a function of temperature:
shifts were measured below the exchange region and extrapolated
into the temperature range where simulations were performed. The
monodimensional NOE experiments of 2 were obtained in CDCl3
at 0 °C13 by means of the DPFGSE-NOE12 sequence. To selectively
irradiate the two 13C satellites, a double-frequency19 10 Hz wide
Calculations. Computations were carried out at the B3LYP/6-
31G(d) level by means of the Gaussian 03 series of programs6 (see
Supporting Information): the standard Berny algorithm in redundant
internal coordinates and default criteria of convergence were
employed. The reported energy values are not ZPE corrected.
Harmonic vibrational frequencies were calculated for all the
stationary points. For each optimized ground state the frequency
analysis showed the absence of imaginary frequencies, whereas each
transition state showed a single imaginary frequency. Visual
inspection of the corresponding normal mode was used to confirm
that the right transition state had been found.
Acknowledgment. L.L. and A.M. received financial support
from the University of Bologna (Funds for selected research
topics and RFO) and MIUR-COFIN 2005, Rome (national
project “Stereoselection in Organic Synthesis”).
(17) Bradley, S. A.; Krishnamurthy, K. Magn. Reson. Chem. 2005, 43,
117. Willker, W.; Leibfritz, D.; Kerssebaum, R.; Bermel, W. Magn. Reson.
Chem. 1993, 31, 287.
(18) Hurd, R. E.; John, B. K. J. Magn. Reson. 1991, 91, 648.
(19) Smallcombe, S. H. J. Am. Chem. Soc. 1993, 115, 4776; Patt, S. J.
Magn. Reson. 1992, 96, 94.
Supporting Information Available: Calculated structures of
conformers of 2, tables of rate constants, 1H and 13C NMR results,
HPLC traces, and computational data for compounds 1-2. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(20) Kupcˇe, E.; Boyd, J.; Campbell, I. D. J. Magn. Reson., Ser. B 1995,
106, 300.
JO070679Q
5394 J. Org. Chem., Vol. 72, No. 14, 2007