Magic acid free generation of antiaromatic dications at room temperature

Article abstract of DOI:10.1021/jo201512n

A new method for the generation of dicationic species via ionization of diols is described. The method makes use of milder reagents at room temperatures, an advantage over use of Magic Acid at -78 °C. A series of mono- and dications were synthesized successfully, including previously unattainable species.

Full text of DOI:10.1021/jo201512n

Note
pubs.acs.org/joc
Magic Acid Free Generation of Antiaromatic Dications at Room
Temperature
Sean P. McClintock† and Nancy S. Mills*
Department of Chemistry, Trinity University, San Antonio, Texas 78212, United States
S
* Supporting Information
ABSTRACT: A new method for the generation of dicationic species via ionization of
diols is described. The method makes use of milder reagents at room temperatures, an
advantage over use of Magic Acid at −78 °C. A series of mono- and dications were
synthesized successfully, including previously unattainable species.
In our survey of the literature we noticed that the acid system
ur laboratory has been actively involved in the
investigation of antiaromatic dications for some time.1
of choice for the ionization of alcohols to carbocations is almost
universally Magic Acid.2−5 However, Gabbai et al. reported that
a mixture of aqueous HBF4 and trifluoroacetic anhydride
(TFAA) could protonate the alcohol groups of a 1,8-
disubstituted naphthalenediol to afford a stable dication after
loss of water (Figure 2).6,7 While 6 is presumably more stable
O
Previously, dications have been synthesized by either the
oxidation of alkene precursors 1 (Figure 1)1a,b or, more
Figure 2. Preparation of dication 6 from diol 5.6
than the dications we are interested in, the synthesis was very
intriguing. It made use of safer reagents, could be done at room
temperature, and was not water or air sensitive.
Attempting this procedure with 3 yielded 4; to our
knowledge, this is the first antiaromatic dication synthesized
at room temperature. Additionally the synthesis was performed
open to the air and in the presence of water (although it is
believed that the TFAA in essence acts as a drying agent for the
HBF4 and the eliminated water). While we were able to
synthesize and characterize the compound by 1D and 2D NMR
spectroscopy (Figure 3), we noticed that the deep red solution
started to turn darker over a period of ca. 30 min, and black
precipitate began to come out of solution. By NMR we noticed
that the peaks of 4 slowly disappeared and were replaced by
broad indistinguishable peaks (seen in Figure 3). It is worthy of
note that the spectra did not match up perfectly with the
published spectra of 4, which is not too surprising given that
the dications are prepared in very different solvents (TFAA
versus SO2ClF1c) and at different temperatures (24 °C versus
Figure 1. Previously studied bisfluorenyl dications and their
generation from neutral species.
recently, the Magic Acid (SbF5·FSO3H) promoted ionization of
diol precursors 3.1c,d As we continued our investigation into
antiaromaticity, in particular the antiaromaticity of indenyl
cations, we began to appreciate the need for a new approach to
dication synthesis. First, while Magic Acid was effective in the
ionization of 3 it was not effective with indenyl diols,
presumably due to the oxidation of the indenyl π bond.
Second, the synthesis required cold temperatures (−78 to −50
°C) for the synthesis and NMR characterization, respectively,
making transfer of viscous reagents at low temperatures more
challenging. Lastly, the synthesis required the use of both SbF5
and SO2ClF, both of which are dangerously water sensitive,
giving off HF upon exposure to trace moisture. Therefore, we
set out to determine a way to make antiaromatic dications that
can be done at room temperature and which does not require
the use of SbF5. Herein we detail our experimental findings.
−
−50 °C) and had different counterions (SbF5·FSO3 versus
Received: July 20, 2011
Published: November 1, 2011
© 2011 American Chemical Society
10254
dx.doi.org/10.1021/jo201512n | J. Org. Chem. 2011, 76, 10254−10257

The Journal of Organic Chemistry
Note
formed in any other system examined. By NMR, 4 showed no
signs of decomposition after 8 h at room temperature and was
still the major component after 4 days (Figure 4). To our
1
Figure 3. H NMR spectra of dication 4 by protonation of 3 with
HBF4 (aq) in TFAA.
−
BF4 ). The experimental shifts match up well with the DFT-
calculated shifts (see the Supporting Information).
1
Figure 4. Stacked H NMR spectra of dication 4 over time at room
While the initial results were exciting, there were a few
shortcomings, primarily that the dications were not particularly
stable and showed decomposition in less than 30 min. Believing
that the instability was related to the solubility of the dications,
we screened a variety of different solvents. We found that
diethyl ether accelerated the precipitation of the material (no
dications observed by NMR), while chlorinated organic
solvents (CH2Cl2 and CHCl3) also failed to cleanly provide
dication 4. THF is incompatible with the superacid reaction
mixture. The use of SO2Cl2 afforded a deep red solution of
dications that showed no precipitation.8
temperature.
astonishment, 4 was still detectable, albeit in small amounts,
after 8 days at room temperature. To date these are the most
stable, longest lasting antiaromatic dications that we or others
have made. The primary advantage to this new procedure for
making dications is the ease of use of the reagents; there is no
need for inert atmosphere techniques and the reactions can be
done at room temperature. This allows for much quicker
turnover between reactions and rapid monitoring by NMR.
Additionally, the conditions do not require the oxidization by
SbF5 and therefore should allow the ionization of diol
precursors that are sensitive to oxidation.
We found that in the examination of several different
superacids (HBF4, HPF6, and FSO3H), addition of TFAA aided
in both the stability of the dications and the resolution of the
spectra. The aqueous acid/TFAA ratio was kept at 1:10, a ratio
that ensured all water would be removed from the aqueous acid
solutions. Increasing the amount of TFAA had no further effect.
With solutions of FSO3H, which contained no water, the TFAA
to acid ratio was reduced to 1:1. Omitting TFAA from the
reaction still led to dication formation but the resultant
dications decomposed faster than the dications containing
TFAA. We found that FSO3H proved to be the best acid; it
provided 4 cleanly and allowed for the study of counterions
To prove the overall utility of our new method and to prove
it comparable to Magic Acid, we set out to explore another
cationic system which has been studied previously using low
temperatures and Magic Acid (Scheme 1). Olah et al. made the
Scheme 1. Synthesis of Monocation 8
such as BF4 , PF6 , SbF6 , and F− more cleanly than did HBF4,
which would also contain a potentially stabilizing counterion.
Through the examination of this series of common counterions,
it was discovered that the counterion did not affect the
chemical shifts of the dications, but did influence the overall
stability. It appears that the size of the counterion is important.
With small counterions such as BF4− and F−, dication 4 showed
signs of decomposition after 8 h, and was not detectable after 4
days. Larger ions such as SbF6− and PF6− were able to stabilize
−
−
−
9-phenylfluorenyl cation (8) in 1980 by treating alcohol 5 with
Magic Acid at −78 °C and characterized the systems using both
1H and 13C NMR spectroscopy.9,10 Using the aforementioned
conditions, 8 was synthesized at room temperature and proved
to be stable for an extended period of time, with no
decomposition evident after 24 h; see the Supporting
Information.
The extended stability and the ambient temperature offer a
sizable advantage over previous methods used to study these
types of molecules. Previously, our group has been unsuccessful
at obtaining 13C NMR data for many dications as the samples
would decompose before a suitable carbon spectrum could be
obtained. Using this new approach, we were successfully able to
−
the dication, with PF6 giving superior stability. Excess
counterion provided for the best stabilization of the dication,
with equi- and submolar ratios giving rise to dications with
shorter lifetimes. This indicates that there is an equilibrium
between the counterion salt and the in situ generated
−
counterion FSO3 and that greater amounts of salt favor the
formation of the more stable complex. Treatment of 3 with
FSO3H, TFAA, and NaPF6 in SO2Cl2 at room temperature
gave rise to dication 4, which was much more stable than 4
10255
dx.doi.org/10.1021/jo201512n | J. Org. Chem. 2011, 76, 10254−10257

The Journal of Organic Chemistry
Note
obtain 13C data for both 4 and 8. Analysis of the two spectra
reveled similarities between the two compounds, particularly
the carbocation centers that appear at δ 205.2 (4) and 204.4
(8) ppm. Because of the ambient temperature, 13C data can be
safely collected overnight without constantly supplying the
spectrometer with liquid nitrogen.
shown that this method can be extended to other cationic
systems and allows for the study of systems under more
desirable conditions. Using these procedures has allowed for
the synthesis of indenyl cations which are not compatible with
Magic Acid.
The ultimate goal of this study, however, was to allow access
to dications that were incompatible with Magic Acid. In our
ongoing study of antiaromaticity, we were interested in the
synthesis of indenyl cations as they are, computationally, more
antiaromatic than the fluorenyl systems that we have been
studying.9 As mentioned previously, attempts to study indenyl
cations such as dication 10 by Magic Acid (1:1 FSO3H/SBF5)
EXPERIMENTAL SECTION
■
General Procedure A for the Formation of Dications. In an
NMR tube, 10 mg of diol was added along with NaPF6 (30 mg) and a
sealed capillary containing acetone-d6. In a separate centrifuge tube
SO2Cl2 (0.5 mL), TFAA (0.25 mL), and FSO3H (0.25 mL) were
combined open to the air and mixed via vortex. Approximately 0.7 mL
of the acid solution was transferred to the NMR tube. The NMR tube
was capped and the sample was analyzed by NMR spectroscopy (500
MHz spectrometer) at 24 °C.
1
protonation were unsuccessful (Figure 5a, Scheme 2). The H
Bisfluorenyl Dication 4. Diol 3 was reacted according to general
procedure A: 1H NMR (acetone-d6) δ 7.60 (s, 4H), 6.78 (t, J = 7.5 Hz,
4H), 6.63 (d, J = 7.6 Hz, 4H), 6.28 (m, 8H); 13C NMR (acetone-d6) δ
205.2, 152.5, 152.0, 144.5, 142.8, 138.3, 134.4, 133.3, 128.0.
9-Phenylflorenyl Cation 8. Alcohol 7 was reacted according to
general procedure A: 1H NMR (acetone-d6) δ 7.61 (t, J = 7.5 Hz, 1H),
7.43 (d, J = 7.4 Hz, 2H), 7.28 (t, J = 7.9 Hz, 2H), 6.82 (t, J = 7.5 Hz,
2H), 6.78 (d, J = 7.6 Hz, 2H), 6.42 (m, 4H); 13C NMR (acetone-d6) δ
204.4, 149.6, 146.9, 142.8, 141.4, 139.8, 134.1, 131.9, 131.8, 130.4,
124.9.
3-Phenylindenyl−Fluorenyl Dication 10. Diol 910 was reacted
according to general procedure A using SO2ClF as a solvent. The
reaction was carried out at −78 °C, and the reaction was monitored by
1H NMR at −50 °C: 1H NMR (acetone-d6) δ 7.73 (br s, 2H), 7.59 (t,
J = 6.9 Hz, 1H), 7.54 (d, J = 7.9 Hz, 2H), 7.33 (d, J = 7.5 Hz, 2H),
7.18 (t, J = 6.9 Hz, 2H), 6.92 (d, J = 7.0 Hz, 1H), 6.59 (m, 5H), 6.48
(d, J = 7.6 Hz, 2H), 6.39 (s, 1H), 6.14 (m, 4H).
Figure 5. 1H NMR spectra of dication 10 taken at −50 °C: (A)
reaction performed using Magic Acid; (B) reaction performed using
FSO3H/TFAA/NaPF6/SO2ClF at −78 °C.
Synthesis of 9-(4-(1-Hydroxy-3-phenyl-1H-inden-1-yl)-
phenyl)-9H-fluoren-9-ol (9). See the Supporting Information for
the synthetic scheme and NMR spectra. In a dry 100 mL round-
bottom flask was dissolved 1,4-dibromobenzene (1.9 g, 8.3 mmol) in
dry THF (41 mL) and the solution cooled to −78 °C under Ar. n-
Butyllithium (3.2 mL, 2.5 M in hexanes) was added dropwise, and the
solution was stirred for 1 h after complete addition. In a separate 250
mL round-bottom flask, 3-phenyl-1-indanone (1.3 g, 6.3 mmol) was
dissolved in dry THF (31 mL) and cooled to −78 °C under Ar. After
the monolithiated dibromobenzene stirred for 1 h at −78 °C, the
lithiate was transferred by cannula to the solution of 3-phenyl-1-
indanone, which was allowed to warm to rt overnight. H2SO4 (30 mL,
5 M) was then added to the reaction and allowed to stir for 20 min.
The reaction was then extracted 3× with diethyl ether and washed
with aq NaHCO3 (1×) and brine (2×). The organic layer was dried
over MgSO4 and filtered through a plug of silica. Column
chromatography of the crude material eluting with hexanes afforded
1-(4-bromophenyl)-3-phenyl-1-indene (1.65 g, 76%) as a yellow solid.
1-(4-Bromophenyl)-3-phenyl-1-indene (1.65 g, 4.75 mmol) and
NaHCO3 (2.0 g, 23.75 mmol) were dissolved in H2O (50 mL) and
EtOAc (50 mL), and the mixture was stirred vigorously with a
magnetic stirrer. Acetone (3.5 mL, 47.5 mmol) was added, and the
biphasic solution was allowed to stir for 10 min. A solution of Oxone
(2.92 g, 4.75 mmol) in H2O (50 mL) was then added by addition
funnel over 1 h. The reaction was monitored by TLC and then
extracted with EtOAc (2×), washed with H2O and brine, and then
dried over MgSO4. The solvent was removed in vacuo. The crude oil
was then dissolved in dry THF (100 mL) and cooled to −78 °C under
Ar. Freshly prepared LDA (2 equiv) was transferred by cannula to the
epoxide, and the reaction was allowed to stir for 3 h as it warmed to rt.
The reaction was quenched with 10% HCl and extracted with diethyl
ether (3×). The crude alcohol was purified by column chromato-
graphy (10% EtOAc in hexanes) to give 1-(4-bromophenyl)-3-phenyl-
1H-inden-1-ol (0.92 g, 54%) as an orange oil.
Scheme 2. Synthesis of Indenyl−Fluorenyl Dication 10
NMR spectrum exhibits broad, indistinguishable peaks.
Attempting the reaction with the newly developed procedure,
however, led only to decomposition. While this was very
disappointing, we considered that the increased antiaromaticity
(and therefore decreased stability) could cause 10 to be
unstable at room temperature. Performing the reaction at −78
°C using SO2ClF as solvent rather than SO2Cl2 successfully
afforded 10 which could be analyzed by 1H NMR spectroscopy.
1
Of special interest is the fact that the H spectrum obtained by
this method is very clean, with well-resolved peaks and a clean
baseline, another advantage over Magic Acid. This is the first
example of an indenyl cation prepared by ionization of an
alcohol precursor.
In summary, we have developed a Magic Acid free method
for synthesizing antiaromatic dications at room temperature.
The milder reaction conditions will allow us to study more
sensitive systems, which we are currently pursuing. We have
1-(4-Bromophenyl)-3-phenyl-1H-inden-1-ol (0.92 g, 2.5 mmol) was
dissolved in dry THF (40 mL) and cooled to −78 °C under Ar. n-
Butyllithium (2.1 mL, 2.5 M in hexanes) was added dropwise and then
10256
dx.doi.org/10.1021/jo201512n | J. Org. Chem. 2011, 76, 10254−10257

The Journal of Organic Chemistry
Note
allowed to stir for 1 h. In a separate flask, fluorenone (0.52 g, 2.9
mmol) was dissolved in dry THF (20 mL), cooled to −78 °C under
Ar, and then transferred by cannula to the lithiate. The reaction was
allowed to warm to rt overnight, quenched with aq NH4Cl, extracted
with diethyl ether (3×), washed with H2O (1×) and brine (1×), and
dried over Na2SO4. The crude alcohol was purified by column
chromatography (20% DCM in hexanes), followed by recrystallization
with toluene/hexanes and preparative TLC on silica with 2:1 hexanes/
toluene, to give 9 (0.53 g, 46%) as a tan solid: 13C NMR (126 MHz,
CDCl3) δ 83.52, 84.47, 120.05, 121.17, 123.71, 124.80, 125.24, 125.48,
126.96, 127.50, 128.36, 128.63, 129.07, 134.49, 138.91, 138.98, 139.50,
evidence of chlorination with SO2Cl2 under these superacid
conditions.
(9) Jiao, H.; Schleyer, P. v. R.; Mo, Y.; McAllister, M. A.; Tidwell, T.
T. J. Am. Chem. Soc. 1997, 119, 7075−7083.
(10) Olah, G. A.; Prakash, G. K. S.; Liang, G.; Westerman, P. W.;
Kunde, K.; Chandrasekhar, J.; Schleyer, P. v. R. J. Am. Chem. Soc. 1980,
102, 4485−4492.
1
140.04, 141.46, 142.40, 143.97, 150.22, 150.24, 150.67; H NMR (500
MHz, CDCl3) δ 7.65 (d, J = 7.5 Hz, 2H), 7.58 (d, J = 8.3 Hz, 2H),
7.49−7.18 (m, 17H), 6.40 (s, 1H). Anal. Calcd for C34H22O2: C,
87.90; H, 5.21; O, 6.89. Found: C, 85.12; H, 5.82. Note: after three
successive methods of purification, we were unable to obtain
analytically pure material. See the Supporting Information for 1H
and 13C NMR spectra that show traces of an impurity.
ASSOCIATED CONTENT
■
S
* Supporting Information
Comparison of computational versus experimental 1H chemical
shifts for 4 and 10; spectroscopic data for 4, 8, and 10;
synthetic scheme and spectral information for 9; Cartesian
coordinates and total energy for 10. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: nmills@trinity.edu.
Present Address
†Department of Physical and Biological Sciences, Western New
England University, Springfield, MA 01119.
ACKNOWLEDGMENTS
■
We thank the Welch Foundation (Grant No. W-794) and the
National Science Foundation (Grant Nos. CHE-0948445,
CHE-0957839, CHE-0553589, and CHE-0126417) for their
support of this research.
REFERENCES
■
(1) For recent publications, see: (a) Mills, N. S.; Cheng, F. E.;
Baylan, J. M.; Tirla, C.; Hartmann, J. L.; Patel, K. C.; Dahl, B. D.;
McClintock, S. P. J. Org. Chem. 2011, 76, 645−653. (b) Piekarski, A.
M.; Mills, N. S.; Yousef, A. J. Am. Chem. Soc. 2008, 130, 14883−14890.
(c) Dahl, B. J.; Mills, N. S. J. Am. Chem. Soc. 2008, 130, 10179−10186.
(d) Dahl, B. J.; Mills, N. S. Org. Lett. 2008, 10, 5605−5608.
(2) Olah, G. A.; Prakash, G. K. S.; Molnar, A.; Sommer, J. Superacid
Chemistry, 2nd ed.; John Wiley and Sons: Hoboken, 2009.
(3) Olah, G. A. Angew. Chem., Int. Ed. Engl. 1995, 34, 1393−1405.
(4) Prakash, G. K. S.; Rawdah, T. N.; Olah, G. A. Angew. Chem., Int.
Ed. Engl. 1983, 22, 390−401.
(5) Olah, G. A.; Schlosberg, R. H. J. Am. Chem. Soc. 1968, 90, 2726−
2727.
(6) Wang, H. W., C. E.; Perez, L. M.; Hall, M. B.; Gabbai, F. P. J. Am.
Chem. Soc. 2004, 126, 8189−8196.
(7) Wang., H.; Gabbai, F. P. Angew. Chem., Int. Ed. Engl. 2004, 43,
184−187.
(8) Solvents SO2 and SO2ClF have been used in the formation of
carbocations since the first use of superacid systems, presumably
because the carbocations were anticipated to be sufficiently unstable
that characterization would require low temperatures, and solvents
which were not viscous at those temperatures. SO2Cl2 seemed to be a
reasonable extension from SO2ClF when we were looking for a solvent
that was more tractable at room temperature. We have seen no
10257
dx.doi.org/10.1021/jo201512n | J. Org. Chem. 2011, 76, 10254−10257