The experimental observation of the intramolecular NO2/CO interaction in solution

Article abstract of DOI:10.1002/anie.201402366

The weak electrostatic interaction between nitro and carbonyl moieties has been observed by means of variable-temperature NMR spectroscopy. Its energetic contribution was evaluated to be about 3 kcal mol^-1 by DFT calculations, and confirmed by the measurement of internal energy barriers to the rotation of suitable nitroaryl rings. Might without muscle: The weak electrostatic interaction between nitro and carbonyl moieties has been observed by means of variable-temperature NMR spectroscopy. Its energetic contribution was evaluated to be about 3 kcal mol^-1 by DFT calculations, and confirmed by the measurement of internal energy barriers to the rotation of suitable nitroaryl rings (see picture).

Full text of DOI:10.1002/anie.201402366

Angewandte
Chemie
DOI: 10.1002/anie.201402366
Weak Interactions
The Experimental Observation of the Intramolecular NO2/CO
Interaction in Solution**
Michel Chiarucci, Alessia Ciogli, Michele Mancinelli, Silvia Ranieri, and Andrea Mazzanti*
Abstract: The weak electrostatic interaction between nitro and
carbonyl moieties has been observed by means of variable-
temperature NMR spectroscopy. Its energetic contribution was
evaluated to be about 3 kcalmolÀ1 by DFT calculations, and
confirmed by the measurement of internal energy barriers to
the rotation of suitable nitroaryl rings.
The design of a chemical system suitable for the obser-
vation of this interaction should consider the potential of the
two acting parts (i.e., the carbonyl and the nitro group) to
move at a great amplitude without significant variation of the
overall conformational energy, to enable the best geometry
for maximum stabilization to be adopted. Such a situation can
be found in biaryl systems, in which the energy minima are
known to be quite flat.[12] At the same time, the chemical
system should generate two different conformations that can
be observed by dynamic NMR spectroscopy.
Weak chemical interactions play a key role in chemistry.
They are effective in many biological systems, and they can be
employed to design supramolecular assemblies and scaf-
folds.[1] Among them, hydrogen bonds,[2] halogen–halogen
bonds,[3] and van der Waals dispersive forces[4] are the most
studied labile interactions. Salt bridges are well-known to
drive protein folding and stability,[5] and electrostatic p–p
interactions have been extensively studied from a theoretical
point of view.[6] Recently, it was shown that noncovalent
interactions can modulate the conformational preferences
and stereoselectivity of some organocatalysts.[7]
We recently reported that bisaryl maleimides (Scheme 1)
yield atropisomers when highly hindered aryl systems are
bound to the 3,4-positions[13] because of the out-of-plane
Some years ago, it was shown that a weak bond due to the
electrostatic interaction between nitrogen and oxygen was
responsible for the stabilization of the crystal structure of
N,N-dipicrylamine,[8] and that the intermolecular N–O inter-
action was one of the driving interactions for the self-
assembly of N-oxalyl-2,4-dinitroanilide in the solid state.[9]
Through-space interactions were also observed in the solid
state for a series of bipyridine N-oxides.[10] Ab initio
calculations[11] had suggested that the energy involved in the
N–O interaction was about 13 kJmolÀ1.
We thus speculated that the weak interaction between
a nitro and a carbonyl group could compete with other weak
interactions in the stabilization of preferred molecular con-
formations in the solid state, as well as in solution, provided
the correct geometries of the two acting partners are met.
Herein we report the first experimental observations of this
weak interaction in solution, and a quantitative measurement
of its strength.
Scheme 1. Structure of the compounds used in this study. Bn=benzyl.
disposition of the two aryl rings. When less-hindered ortho-
substituted aryl systems are bound to the 3,4-positions of
maleimide, the rotational barriers are smaller; nevertheless,
they could be detected by dynamic NMR spectroscopy.[14] We
envisaged that this particular system fulfilled the required
features for us to study the intramolecular NO2/CO inter-
action.
DFT computational studies and dynamic NMR spectro-
scopic data showed that the energies of the syn and anti
conformers were very similar when aliphatic ortho-aryl
substituents were employed, despite the differences in the
steric requirements in the ground states and the huge range of
experimental interconversion barriers (12.9–26.0 kcal
molÀ1).[13] In contrast, the same calculations suggested that
in the case of compound 1, which bears two o-nitrophenyl
groups, the anti conformer was more stable than the syn
conformer by more than 4 kcalmolÀ1 (at the B3LYP/6-31G(d)
level), thus implying that only the anti conformer should be
populated. From a steric point of view, the nitro group is very
similar to the methyl group;[15] thus steric considerations
cannot explain the large stabilization of the anti conforma-
tion. Calculations at the B3LYP/def2-TZVP, B97D/def2-
TZVP, wB97XD/def2-TZVP, and wB97XD/6-311 ++ G-
[*] Dr. M. Chiarucci, Dr. M. Mancinelli, S. Ranieri, Prof. Dr. A. Mazzanti
Department of Industrial Chemistry “Toso Montanari”
Alma Mater Studiorum—University of Bologna
Viale Risorgimento 4, 40136 Bologna (Italy)
E-mail: andrea.mazzanti@unibo.it
Homepage: http://www2.fci.unibo.it/~mazzand
Dr. A. Ciogli
Dipartimento di Chimica e Tecnologie del Farmaco
Universitꢀ di Roma “La Sapienza”
Piazzale A.Moro 5, 00185 Roma (Italy)
[**] We acknowledge the Universitꢀ di Bologna (RFO funds).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201402366.
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
(2d,p) levels confirmed the large stabilization of the anti
conformer with respect to the syn conformer (see Table 1). A
bias due to the previous theoretical approach seems therefore
to be unlikely.
although in that case the interaction was intermolecular and
in the solid state.[2c,9] Such an interaction could also take place
in the syn conformer, but in this case only one stabilizing
interaction could be effective, because the second interaction
would drive the opposite sides of the phenyl rings close to
each other, thus generating a destabilizing steric clash.
Compound 1 was crystallized from a solution in acetoni-
trile, and the solid-state structure fully confirmed the
hypothesis of the calculations. Only the anti conformer is
present in the centrosymmetric unit cell, and both nitro
groups interact with the two carbonyl groups.[16] In each case,
the oxygen atom of the carbonyl group lies exactly orthogonal
to the plane of the nitro group; thus, the electrostatic
interaction of the electron-rich oxygen atom with the
electron-poor nitrogen atom is possible, as well as the
interaction of one oxygen atom of the nitro group with the
carbon atom of the carbonyl group. The N–O and O–C
distances are very similar to those reported.[8] The skew angles
of the two o-nitrophenyl rings were calculated to be À578,
whereas the experimentally found angles were À498 and
À558.
Table 1: Summary of calculations.[a]
Compd Level of calculation
DH8
anti/syn
(exptl)
[kcalmolÀ1 [b]
]
1
1
1
1
1
2
3
4
4
4
5
6
7
8
B3LYP/6-31G(d)
B3LYP/def2-TZVP
B97D/def2-TZVP
wB97XD/def2-TZVP
wB97XD/6-311+ +G(2d,p)
4.1
4.0
2.6
3.3
3.0
>99.5:0.5
wB97XD/6-311+ +G(2d,p) À0.6
21:79[c]
45:55[d]
>99.5:0.5
wB97XD/6-311+ +G(2d,p) À0.2
B3LYP/def2-TZVP
4.6
4.0
4.0
1.1
0.4
0.9
0.7
wB97XD/def2-TZVP
wB97XD/6-311+ +G(2d,p)
wB97XD/6-311+ +G(2d,p)
wB97XD/6-311+ +G(2d,p)
wB97XD/6-311+ +G(2d,p)
wB97XD/6-311+ +G(2d,p)
68:32[c]
59:41[c]
67:33[e]
58:42[e]
To determine whether this interaction could also be
observed experimentally in solution, we acquired variable-
temperature NMR spectra. When a sample of 1 in CDCl3 was
cooled to À248C, the broad signal of the benzylic CH2 group
was split into an AB system, and no signals ascribable to
a second conformer could be detected (Figure 2). This result
[a] All calculated energies are ZPE-corrected enthalpies (ZPE=zero-
point energy). [b] A negative value means that the syn conformation is
calculated to more stable than the anti conformation. [c] The ratio was
determined from the NOE NMR spectrum. [d] Ref. [13]. [e] The ratio was
assigned on the basis of calculations.
A close examination of the optimized structures showed
that, on each side of the maleimide ring, an electrostatic
interaction took place between the electron-rich oxygen atom
of the carbonyl group and the nitrogen atom of the nitro
group. A second electrostatic interaction was present, with
reverse polarity, between one of the oxygen atoms of the nitro
group and the electron-poor carbon atom of the carbonyl
group (Figure 1). The calculated distance between the oxygen
atom of the carbonyl group and the nitrogen atom was very
similar to that observed for N-oxalyldinitroanilide (2.85 ꢀ),
Figure 2. Variable-temperature 1H NMR spectra of 1 (600 MHz in
CDCl3). Left: experimental spectra. Right: simulated spectra with the
relative rate constants.
implies that the rotation of the o-nitrophenyl groups was
frozen and that the single observed conformation did
correspond to the anti geometry (C2 symmetry).[17] The
racemization barrier due to rotation of the o-nitrophenyl
rings was derived by lineshape simulation as 14.2 Æ 0.2 kcal
molÀ1. This value is matched very well by the value of
14.3 kcalmolÀ1 found by DFT calculations (or 13.5 kcalmolÀ1
if the ZPE-corrected enthalpy is considered).
Figure 1. Top: X-ray crystal structure of compound 1. Bottom: calcu-
lated structures of the anti and syn conformers at the wB97XD/6-
311+ +G(2d,p) level. Distances in ꢁ.
2
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
The absence of the syn conformer at À248C provided
suitable information about the stabilization energy involved
in the electrostatic interactions. If a 99.5 :0.5 ratio at À248C is
taken into account,[18] the corresponding energy difference
(DG8) is 2.6 kcalmolÀ1. This value is the lower limit for the
stabilization of the anti conformation because the syn
conformer was not detectable at all. As one NO2/CO
interaction is available in both conformations, the value
should be considered a direct measurement of the strength of
the electrostatic interaction. The value nicely matches the
DFT-predicted value (2.6 Æ 4.1 kcalmolÀ1; see Table 1).[19]
For the following considerations, it should be taken into
account that the electrostatic interaction shrinks the dihedral
angle between the maleimide and o-nitrophenyl rings towards
the geometry of the transition state, in which the aryl ring is
coplanar to the maleimide ring. At the same time, the motion
of one ring towards the transition state forces the second ring
to become perpendicular with respect to the maleimide plane,
to minimize the steric interaction between the two rings (see
Figure S1 in the Supporting Information). The displacement
of the second ring weakens the NO2/CO interaction, and the
observed energy barrier is the result of the sum of these two
contributions (i.e. the steric clash between the rotating ring
and the maleimide ring, and a partial loss of the NO2/CO
stabilization for the second ring).
Scheme 2. DMC cycle for compounds 1–3. The indicated values (in
kcalmolÀ1) are the energy differences (DG8) between the anti and syn
conformers as measured by NMR spectroscopy at À408C. Negative
values indicate that the syn conformation is more stable than the anti
conformation.
and double mutant with respect to compound 1 (Scheme 2).
By using this approach and the lower energy-difference limit
determined for 1 (i.e. 2.6 kcalmolÀ1), we calculated that the
stabilization due to the electrostatic interaction corresponds
to 3.35 kcalmolÀ1.
Having found an example for which the electrostatic
interaction can be observed, we searched for more examples
and for a quantitative evaluation of its energetic contribution
(Scheme 1). Compound 2 bears one o-nitrophenyl and one o-
tolyl ring. Whereas the nitro group can be involved in the
NO2/CO interaction, the disposition of the o-tolyl ring is
driven only by steric factors. Indeed, the low-temperature
NMR spectrum of 2 at À418C in C2D2Cl4 (see Figure S2)
showed that both conformations were populated in a 71:29
ratio, and NOE spectra showed that the syn conformation was
To check whether the NO2/CO interaction was restricted
to the geometric constraints of the pentaatomic scaffold of
maleimide, we prepared compounds 4–6 containing the 1,4-
naphthoquinone scaffold. Within this series, the anti confor-
mer of compound 4 should gain stabilization from two NO2/
CO interactions, whereas in compounds 5 and 6, both
conformers should be populated. DFT calculations at the
B3LYP/def2-TZVP, wB97XD/def2-TZVP, and wB97XD/6-
311 ++ G(2d,p) levels suggested that in the case of compound
4, the anti conformer was more stable than the syn conformer
by at least 4.0 kcalmolÀ1 (Table 1), whereas for 5 and 6, the
two conformers were calculated to be very close in energy.
The 1H NMR spectrum of 4 at + 258C showed a single set
of signals, whereas the spectra of 5 and 6 revealed the
presence of both the conformers in a 68:32 and 59:41 ratio,
respectively. The anti conformation was confirmed in both the
latter compounds to be the more abundant on the basis of
NOE spectra (see Figures S8 and S9). The energy barriers for
the o-nitrophenyl rotation were calculated for compounds 4
and 5 as 22.7 and 22.3 kcalmolÀ1, respectively, and as
21.0 kcalmolÀ1 for the o-tolyl rotation in 6. As they are
inaccessible for the dynamic NMR spectroscopic technique,
the energy barriers for compounds 5 and 6 were determined
by 1D EXSY, which yielded barriers of 21.0 Æ 0.2 and 20.7 Æ
0.2 kcalmolÀ1, respectively (see Figure S10). Thus, in the case
of 4, the ambient-temperature NMR spectrum should display
the presence of a second conformation, if it were populated.
The absence of a suitable chirality probe did not allow the
determination of whether the single conformer observed in
the NMR spectra of 4 corresponded to the anti or to the syn
1
the more populated conformation (see Figure S3).[20] The H
methyl signal is split only when the two conformers are
generated; thus, it indicates the smaller of the two rotational
barriers of the two aromatic rings. On the other hand, the CH2
group is a chirality probe that indicates the formation of the
enantiomeric pair generated by the frozen rotation of the ring
with the higher rotational barrier. The simulation of the
methyl signal provided a value of 12.6 Æ 0.2 kcalmolÀ1 for the
syn/anti interconversion, and the energy barrier derived from
the simulation of the benzylic CH2 group was very similar
(12.9 Æ 0.2 kcalmolÀ1; see Figures S4 and S5).[21] The equiv-
alent rotational barriers confirmed that the methyl and nitro
groups are isosteric,[15,22] and the reliable assignment of the
two measured barriers is impossible. Nevertheless, both
barriers are significantly lower than that of compound 1,
thus confirming a substantial contribution to the ground-state
stabilization in the case of 1. Similarly, we found for
compound 3 a syn/anti ratio of 55:45, equivalent to DG8 =
0.09 kcalmolÀ1 (see Figure S6).
Having established the experimental ratio of the two
conformations of 2 and 3, we could evaluate the energetic
contribution of the electrostatic interaction by using com-
pounds 1–3 as the components of a chemical double-mutant
cycle (DMC),[4c,23] in which compounds 2 and 3 are the single
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
conformer. X-ray diffraction showed that only the anti
conformer was present in the solid state, with NO2/CO
distances and geometries very similar to those in compound
are completely independent. Nevertheless, two NO2/CO
interactions can be effective, and the ground state of both
the syn and anti conformers can be stabilized in the same way
by the electrostatic interaction. Compound 8 shares the same
situation, but the rotational barrier is now driven only by
steric effects. The transition states for the aryl-ring rotation
correspond to a geometry in which the ortho substituent of
the rotating ring is close to the hydrogen atom in the 3-
position (or 6-position), and the syn/anti interconversion
needs the rotation of only one ring. As the nitro and methyl
moieties are isosteric, the barrier for rotation is mainly due to
the stabilization of the ground state.[27] Thus, the rotational
energy difference for the syn/anti interconversion between 7
and 8 has to be assigned to the stabilization due to a single
1
1 (see Figure S7). The ambient-temperature H NMR spec-
trum recorded in a chiral environment[24] showed the splitting
of some aromatic signals, thus confirming that the o-nitro-
phenyl rotation was frozen. Unfortunately, the observed
splitting did not allow the unambiguous assignment of the anti
geometry to the single observed conformation because the
signals of the syn conformer would also be split by the
enantiomerically pure environment.[25]
Compound 4 was therefore analyzed by enantioselective
HPLC, which showed two peaks undergoing dynamic
exchange at + 258C. At 08C, the two chromatographic
peaks were well-resolved, and electronic circular dichroism
(ECD) at 280 nm showed that they had opposite sign
(Figure 3). Thus, we were able to unambiguously confirm
1
NO2/CO interaction. At À658C, the H NMR spectrum of 7
showed that both conformations were populated in a 67:33
ratio, whereas the spectrum of 8 at À1188C showed a 58:42
ratio (see Figures S12 and S13). The energy barrier for the
syn/anti interconversion of 7 was found to be 12.0 Æ 0.2 kcal
molÀ1, whereas the barrier for 8 was found to be 9.1 Æ
0.2 kcalmolÀ1. Thus, the stabilization due to a single NO2/
CO interaction was evaluated to be 2.9 kcalmolÀ1, in agree-
ment with the previous considerations.
In conclusion, we have documented the observation of the
weak NO2/CO electrostatic interaction in solution. The
energetic contributions were established by means of DFT
calculations and dynamic NMR spectroscopy, and by the use
of the DMC approach. Further investigations on other
chemical systems potentially suitable for gaining a deeper
understanding of this interaction are currently in progress.
Received: February 13, 2014
Revised: March 11, 2014
Published online: && &&, &&&&
Keywords: atropisomerism · density functional calculations ·
.
dynamic NMR spectroscopy · maleimides · weak interactions
[1] M. D. Ward, P. R. Raithby, Chem. Soc. Rev. 2013, 42, 1619 – 1636,
and references therein.
Figure 3. Chromatograms of compound 4 on an enantioselective
(R,R)-Whelk-O1 HPLC column, recorded at 08C. Bottom trace: UV
detector. Top trace: ECD detector at 280 nm.
[2] a) B. U. Emenike, W. R. Carroll, J. D. Roberts, J. Org. Chem.
2013, 78, 2005 – 2011; b) P. I. Nagy, J. Phys. Chem. A 2013, 117,
2812 – 2826; c) G. R. Desiraju, Acc. Chem. Res. 1996, 29, 441 –
449; d) T. Steiner, Angew. Chem. 2002, 114, 50 – 80; Angew.
Chem. Int. Ed. 2002, 41, 48 – 76.
[3] a) T. Pilati, F. Cozzi, CrystEngComm 2011, 13, 4549 – 4556;
b) R. O. Fuller, C. S. Griffith, G. A. Koutsantonis, K. M. Lapere,
B. W. Skelton, M. A. Spackman, A. H. White, D. A. Wild,
CrystEngComm 2012, 14, 804 – 811; c) P. Metrangolo, H. Neu-
kirch, T. Pilati, G. Resnati, Acc. Chem. Res. 2005, 38, 386 – 395.
[4] a) C. A. Hunter, Angew. Chem. 2004, 116, 5424 – 5439; Angew.
Chem. Int. Ed. 2004, 43, 5310 – 5324; b) S. Ehrlich, H. F.
Bettinger, S. Grimme, Angew. Chem. 2013, 125, 11092 – 11096;
Angew. Chem. Int. Ed. 2013, 52, 10892 – 10895; c) L. Yang, C.
Adam, G. S. Nichol, S. L. Cockroft, Nat. Chem. 2013, 5, 1006 –
1010; d) I. K. Matia, S. L. Cockroft, Chem. Soc. Rev. 2010, 39,
4195 – 4205.
the presence of solely the enantiomeric pair of the anti
conformation, and also to evaluate the racemization barrier as
20.5 Æ 0.3 kcalmolÀ1 by means of dynamic HPLC[26] (see
Figure S11). By applying the same approach used for 1 to the
case of compound 4, we determined that the stabilization
energy of the anti conformation has to be larger than
2.6 kcalmolÀ1. The application of the DMC approach to the
present situation (compounds 4–6) then yielded a lower limit
of 1.9 kcalmolÀ1 for the stabilization energy.
As a final attempt to experimentally measure the electro-
static interaction without any interference caused by the
proximity of the aryl rings, we prepared compounds 7 and 8.
The 1,4-benzoquinone scaffold of compound 7 bears two o-
nitrophenyl rings in the 2,5-positions; hence, their rotations
[5] S. Kumar, R. Nussinov, ChemBioChem 2002, 3, 604 – 617.
[6] a) E. G. Hohenstein, J. Duan, C. D. Sherrill, J. Am. Chem. Soc.
2011, 133, 13244 – 13247; b) M. Watt, L. K. E. Hardebeck, C. C.
4
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
Kirkpatrick, M. Lewis, J. Am. Chem. Soc. 2011, 133, 3854 – 3862,
and references therein.
[7] M. C. Holland, S. Paul, W. B. Schweizer, K. Bergander, C. Mꢁck-
Lichtenfeld, S. Lakhdar, H. Mayr, R. Gilmour, Angew. Chem.
2013, 125, 8125 – 8129; Angew. Chem. Int. Ed. 2013, 52, 7967 –
7971.
[19] To ascertain whether this interaction was sensitive to hydrogen-
bonding solvents, we also recorded the variable-temperature
NMR spectrum in CD3OD at À308C and found no modification
of the energy barrier and no evidence for a second conformer.
[20] In this case, the benzylic CH2 group corresponded to an AB
system for both conformers, and the major conformer was
assigned as syn on the basis of NOE experiments (see the
Supporting Information).
[8] Z. Yin, L. Jiang, J. Hea, J.-P. Cheng, Chem. Commun. 2003,
2326 – 2327.
[9] a) T. Steiner, Chem. Commun. 1997, 727 – 734; b) G. R. Desiraju,
T. Steiner, The Hydrogen Bond in Structural Chemistry and
Biology, Oxford University Press, Oxford, 1999.
[10] J. OꢂLearly, J. D. Wallis, CrystEngComm 2007, 9, 941 – 950.
[11] J. A. Platts, S. T. Howard, K. Wozniak, Chem. Phys. Lett. 1995,
232, 479 – 485.
[21] The two barriers are certainly different, because the two
simulations of the methyl and CH2 groups were performed on
the same spectra; in this way, the main source of error could be
removed.[14]
[22] R. Ruzziconi, S. Spizzichino, L. Lunazzi, A. Mazzanti, M.
Schlosser, Chem. Eur. J. 2009, 15, 2645 – 2652.
[12] S. Arulmozhiraja, P. C. Selvin, T. Fujii, J. Phys. Chem. A 2002,
106, 1765 – 1769.
[13] M. Ambrogi, A. Ciogli, M. Mancinelli, S. Ranieri, A. Mazzanti, J.
Org. Chem. 2013, 78, 3709 – 3719.
[14] D. Casarini, L. Lunazzi, A. Mazzanti, Eur. J. Org. Chem. 2010,
2035 – 2056.
[15] L. Lunazzi, M. Mancinelli, A. Mazzanti, S. Lepri, R. Ruzziconi,
M. Schlosser, Org. Biomol. Chem. 2012, 10, 1847 – 1855.
[16] CCDC 985950 and 985951 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif, see ESI for details.
[17] The CH2 group acts as a chirality probe and its signal would not
be split in the syn conformer, see: a) W. B. Jennings, Chem. Rev.
1975, 75, 307 – 322; b) K. Mislow, M. Raban, Top. Stereochem.
1967, 1, 1 – 38.
[23] a) A. Horovitz, A. R. Fersht, J. Mol. Biol. 1990, 214, 613 – 617;
b) S. L. Cockroft, C. A. Hunter, Chem. Soc. Rev. 2007, 36, 172 –
188.
[24] Use was made of enantiomerically pure (R)-(À)-trifluoroan-
thrylethanol; see: a) W. H. Pirkle, M. S. Hoekstra, J. Am. Chem.
Soc. 1976, 98, 1832 – 1839; b) W. H. Pirkle, D. L. Sikkenga, J.
Org. Chem. 1977, 42, 1370 – 1374.
[25] L. Lunazzi, M. Mancinelli, A. Mazzanti, J. Org. Chem. 2008, 73,
5354 – 5359.
[26] a) C. Wolf, Chem. Soc. Rev. 2005, 34, 595 – 608; b) I. DꢂAcquar-
ica, F. Gasparrini, M. Pierini, C. Villani, G. Zappia, J. Sep. Sci.
2006, 29, 1508 – 1516; c) F. Piron, N. Vanthuyne, B. Joulin, J.-V.
Naubron, C. Cismas¸, A. Terec, R. A. Varga, C. Roussel, J.
Roncali, I. Grosu, J. Org. Chem. 2009, 74, 9062 – 9070.
[27] The small difference in the observed conformer ratio between 7
and 8 could stem from different interactions with the solvent.
[18] L. Lunazzi, A. Mazzanti, D. Casarini, O. De Lucchi, F. Fabris, J.
Org. Chem. 2000, 65, 883 – 888.
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
Weak Interactions
Might without muscle: The weak electro-
static interaction between nitro and car-
bonyl moieties has been observed by
means of variable-temperature NMR
spectroscopy. Its energetic contribution
was evaluated to be about 3 kcalmolÀ1 by
DFT calculations, and confirmed by the
measurement of internal energy barriers
to the rotation of suitable nitroaryl rings
(see picture).
M. Chiarucci, A. Ciogli, M. Mancinelli,
S. Ranieri, A. Mazzanti*
&&&& — &&&&
The Experimental Observation of the
Intramolecular NO2/CO Interaction in
Solution
6
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
These are not the final page numbers!