Naphthalene-1,8-diylbis(diphenylmethylium) as an organic two-electron oxidant: Benzidine synthesis via oxidative self-coupling of N,N-dialkylanilines

Article abstract of DOI:10.1021/jo060662s

Naphthalene-1,8-diylbis(diphenylmethylium) exhibits a unique electron-transfer reduction behavior due to the close proximity of the two triarylmethyl cations, which form a C-C bond while accepting two electrons, leading to 1,1,2,2-tetraphenylacenaphthene. The preparation of the dication was readily accomplished under anhydrous conditions starting from a cyclic bis(triarylmethyl) ether, derived from 1,8-dibromonaphthalene. The process proceeded via deoxygenation accompanying the formation of a disiloxane on treatment with a silylating agent (Me₃SiClO₄ or Me ₃SiOTf) in 1,1,1,3,3,3-hexafluoropropan-2-ol. The dication was successfully employed for oxidative coupling of N,N-dialkylanilines at the paraposition to afford the corresponding benzidines in good to excellent yield.

Full text of DOI:10.1021/jo060662s

Naphthalene-1,8-diylbis(diphenylmethylium) as an Organic
Two-Electron Oxidant: Benzidine Synthesis via Oxidative
Self-Coupling of N,N-Dialkylanilines
Terunobu Saitoh, Suguru Yoshida, and Junji Ichikawa*
Department of Chemistry, Graduate School of Science, The UniVersity of Tokyo,
Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
junji@chem.s.u-tokyo.ac.jp
ReceiVed March 28, 2006
Naphthalene-1,8-diylbis(diphenylmethylium) exhibits a unique electron-transfer reduction behavior due
to the close proximity of the two triarylmethyl cations, which form a C-C bond while accepting two
electrons, leading to 1,1,2,2-tetraphenylacenaphthene. The preparation of the dication was readily
accomplished under anhydrous conditions starting from a cyclic bis(triarylmethyl) ether, derived from
1,8-dibromonaphthalene. The process proceeded via deoxygenation accompanying the formation of a
disiloxane on treatment with a silylating agent (Me3SiClO4 or Me3SiOTf) in 1,1,1,3,3,3-hexafluoropropan-
2-ol. The dication was successfully employed for oxidative coupling of N,N-dialkylanilines at the para-
position to afford the corresponding benzidines in good to excellent yield.
Introduction
electrochemical properties. These dications were reduced with
two electrons leading to the corresponding stable neutral
compounds 1,1,1,2,2,2-hexaarylethane derivatives, as exempli-
Carbocations generally exist as short-lived intermediates,
which are immediately converted to more stable compounds
via reactions such as rearrangement, elimination, and addition.
While the detailed studies of carbocations with NMR, IR, and
X-ray crystal structure analysis have been accomplished by Olah
and others,1 their applications as synthetic reagents are still
limited. Among them, triarylmethyliums, which are rather stable
carbocations and are readily prepared from the corresponding
alcohols or halides,2 constitute a class of versatile carbocations
with functions3 such as hydride and alkoxy abstraction4 and
Lewis acid catalysis.5
(3) Encyclopedia of Reagents for Organic Synthesis; Paquette, L. A.,
Ed.; John Wiley & Sons Ltd.: Chichester, UK, 1995; Vol. 8, pp 5348-
5357.
(4) (a) Fretzen, A.; Ku¨ndig, E. P. HelV. Chim. Acta 1997, 80, 2023. (b)
Rubio, A.; Liebskind, L. S. J. Am. Chem. Soc. 1993, 115, 891. (c) Pearson,
A. J.; Zettler, M. W. J. Am. Chem. Soc. 1989, 111, 3908.
(5) (a) Mukaiyama, T.; Tamura, M.; Kobayashi, S. Chem. Lett. 1986,
1017. (b) Kobayashi, S.; Murakami, M.; Mukaiyama, T. Chem. Lett. 1985,
1535. (c) Mukaiyama, T.; Kobayashi, S.; Shoda, S. Chem. Lett. 1984, 1529.
(d) Bochkov, A. F.; Kochetkov, N. K. Carbohydr. Res. 1975, 39, 355.
(6) (a) Carey, K. A.; Clegg, W.; Elsegood, M. R. J.; Golding, B. T.;
Hill, M. N. S.; Maskill, H. J. Chem. Soc., Perkin Trans. 1 2002, 2673. (b)
Suzuki, T.; Nishida, J.; Tsuji, T. Chem. Commun. 1998, 2193. (c) Suzuki,
T.; Nishida, J.; Tsuji, T. Angew. Chem., Int. Ed. Engl. 1997, 36, 1329.
(7) Suzuki, T.; Yamamoto, R.; Higuchi, H.; Hirota, E.; Ohkita, M.; Tsuji,
T. J. Chem. Soc., Perkin Trans. 2 2002, 1937.
(8) (a) Wang, H.; Gabba¨ı, F. P. Org. Lett. 2005, 7, 283. (b) Wang, H.;
Webster, C. E.; Perez, L. M.; Hall, M. B.; Gabba¨ı, F. P. J. Am. Chem. Soc.
2004, 126, 8189. (c) Wang, H.; Gabba¨ı, F. P. Angew. Chem., Int. Ed. 2004,
43, 184. (d) Kawai, H.; Takeda, T.; Fujiwara, K.; Suzuki, T. Tetrahedron
Lett. 2004, 45, 8289. See also: (e) Kawai, H.; Nagasu, T.; Takeda, T.;
Fujiwara, K.; Tsuji, T.; Ohkita, M.; Nishida, J.; Suzuki, T. Tetrahedron
Lett. 2004, 45, 4553. (f) Suzuki, T.; Nagasu, T.; Kawai, H.; Fujiwara, K.;
Tsuji, T. Tetrahedron Lett. 2003, 44, 6095.
Recently, dicationic systems in which two triarylmethylium
ions were linked by a carbon skeleton, such as 1,1′-biphenyl-
2,2′-diyl,6 1,1′-binaphthalene-2,2′-diyl,7 and naphthalene-1,8-
diyl8,9 groups, have been prepared and exhibited unique
* Author to whom correspondence should be addressed. Phone/Fax: +81-
3-5841-4345.
(1) (a) Carbocation Chemistry; Olah, A. G., Prakash, G. K. S., Eds.;
Wiley-Interscience: New York, 2004. (b) Olah, A. G. J. Org. Chem. 2001,
66, 5943 and references therein.
(2) (a) Lambert, J. B.; Schulz, W. J., Jr.; McConnell, J. A.; Schilf, W. J.
Am. Chem. Soc. 1988, 110, 2201. (b) Fukui, K.; Ohkubo, K.; Yamabe, T.
Bull. Chem. Soc. Jpn. 1969, 42, 312.
(9) (a) Saitoh, T.; Ichikawa, J. J. Am. Chem. Soc. 2005, 127, 9696. (b)
Saitoh, T.; Yoshida, S.; Ichikawa, J. Org. Lett. 2004, 6, 4563.
10.1021/jo060662s CCC: $33.50 © 2006 American Chemical Society
Published on Web 07/22/2006
6414
J. Org. Chem. 2006, 71, 6414-6419

Bis(triarylmethylium) as Two-Electron Oxidant
TABLE 1. Preparation of
Naphthylene-1,8-diylbis(diarylmethylium) Salts 1a-c
SCHEME 1. Dication as an Organic Two-Electron Oxidant
fied in Scheme 1. Such C-C bond formation between two
carbocation centers was not observed in the one-electron
reduction of triphenylmethylium (trityl cation), which afforded
a dimer with a quinoid structure.10
entry
Ar
X
solvent
1/%
1
2
3
4
5
6
C6H5
C6H5
C6H5
C6H5
C6H5
ClO4
ClO4
ClO4
ClO4
OTf
CH2Cl2
toluene
benzene
HFIP
HFIP
HFIP
no reaction
no reaction
no reaction
93 (1a)
99 (1b)
76 (1c)
Bis(triarylmethylium) 1 (Ar ) Ph) with a naphthalene-1,8-
-
diyl tether was first introduced by Gabba¨ı as the BF4 salt,8b
-
C6H4-4-OMe
ClO4
and we accomplished an independent synthesis of the ClO4
and TfO- salts.9b Dication 1 has two cationic centers in closest
proximity, which brings about an especially high reduction peak
potential compared with those of other bis(triarylmethylium)s
and triarylmethyliums in cyclic voltammogram analysis.8a,c
Moreover, steric congestion around the cationic centers in 1
prevents nucleophilic attack at the carbocation, which might
allow oxidation of nucleophilic species. Despite these advantages
as a reagent for electron-transfer oxidation, there had been no
reports on its application in organic synthesis until our recent
reports.9
N,N,N′,N′-Tetraarylated benzidines have recently received
much interest because of their tunable electric conductivity,
which finds diverse applications such as organic light-emitting
diodes, organic field-effect transistors, organic solar cells, and
organic photoconductors.11a Oxidative coupling of aniline
derivatives provides efficient access to benzidines. Although
several methods for the oxidative coupling with clay,12a a molten
salt,12b a peroxide,12c VCl4,12d or an electrochemical process13
have been reported, most of them are low-yielding processes.
Among these methods, TiCl4-mediated oxidative coupling
seemed the most practical to afford benzidines, despite the
requirement of a large excess amount of starting anilines.11
These facts prompted us to use dication 1 in the electron-
transfer oxidation of N,N-dialkylanilines, nucleophilic substrates.
We have thus achieved the synthesis of benzidines via oxidative
coupling of a variety of anilines. After our preliminary report,9b
Xi’s group reported practical methods for a similar coupling
with Ce(NH4)2(NO3)6 (CAN)14a or CuBr/H2O2,14b although
neither approach was applied to anilines functionalized on the
benzene rings. On the other hand, reductive coupling of
4-haloanilines with a palladium catalyst (Ullmann-type coupling)
readily occurred to produce benzidines in good yield under mild
conditions, although its scope for benzidine synthesis is
unclear.15
and their application as a new organic oxidant to the coupling
reaction of aniline derivatives leading to benzidine synthesis.
Results and Discussion
(a) Preparation of Dications 1. Bis(triarylmethylium)s with
a carbon tether were previously prepared on treatment of the
corresponding diols with aqueous HBF4 or HClO4 in Ac2O,
(EtCO)2O, or (CF3CO)2O.6-8 These methods had a drawback
in purification of the produced dications, due to the low volatility
of water, acid anhydrides, and in situ-generated carboxylic acids.
Therefore, the development of a convenient and practical method
for the dications was still required to isolate them in a pure
form so that they could be used as synthetic reagents. Our
synthetic plan relied on the following two features: (1) dications
1 would be generated from cyclic ethers 5 via deoxygenation
and (2) this process would proceed readily in 1,1,1,3,3,3-
hexafluoropropan-2-ol (HFIP) solvent (Table 1). Treatment of
5 with a strong silylating agent was expected to allow removal
of the oxygen as a disiloxane (R3SiOSiR3), leading to the desired
dications under anhydrous conditions. HFIP would assist the
generation of the dications and be easily removed afterward,
due to its strong ionizing power, low nucleophilicity, and high
volatility.16
Benzophenones were added to the dilithium species, prepared
by treating 1,8-dibromonaphthalene 3 with n-BuLi, to afford
the crude diols 4.17 On successive treatment of their CH2Cl2
solution with a catalytic amount of CF3CO2H and then MeOH,
cyclic ethers 5a and 5b (the precursors of dications 1a-c) were
obtained as white crystals in 80% and 48% yield from 3 by
filtration, respectively (Scheme 2). Thus, neither extraction nor
purification was needed to isolate 5. The procedure for cyclic
ethers 5 was also applied to the preparation of cyclic ether 8
(the precursor of dication 9) starting from diester 6.18
Cyclic ether 5a was treated with Me3SiClO4, prepared in situ
from AgClO4 and Me3SiCl in toluene,19 to deoxygenate it.
Whereas 5a was recovered unchanged in CH2Cl2, toluene, or
benzene, only HFIP allowed deoxygenation of 5a successfully
as expected to afford the desired dication 1a (X ) ClO4) in
Herein we give a full account of a convenient method for
the preparation of naphthalene-1,8-diylbis(diarylmethylium)s 1
(10) Mcbride, J. M. Tetrahedron 1974, 30, 2009.
(11) (a) Gerstner, P.; Rohde, D.; Hartmann, H. Synthesis 2002, 2487
and references therein. (b) Periasamy, M.; Jayakumar, K. N.; Bharathi, P.
J. Org. Chem. 2000, 65, 3548.
(12) (a) Lo´pez-Corte´s, J. G.; Penieres-Carrillo, G.; Ortega-Alfaro, M.
C.; Gutie´rrez-Pe´rez, R.; Toscano, R. A.; Alvarez-Toledano, C. Can. J. Chem.
2000, 78, 1299. (b) Imaizumi, H.; Sekiguchi, S.; Matsui, K. Bull. Chem.
Soc. Jpn. 1977, 50, 948. (c) Naylor, F. T.; Saunders, B. C. J. Chem. Soc.
1950, 3519. (d) Carrick, W. L.; Karapinka, G. L.; Kwiatkowski, G. T. J.
Org. Chem. 1969, 34, 2388.
(15) (a) Kuroboshi, M.; Waki, Y.; Tanaka, H. J. Org. Chem. 2003, 68,
3938. (b) Li, J.-H.; Xie, Y.-X.; Yin, D.-L. J. Org. Chem. 2003, 68, 9867.
(16) (a) Schadt, F. L.; Schleyer, P. v. R. Tetrahedron Lett. 1974, 27,
2335. (b) For recent reports on the cationic reactions conducted in HFIP,
see: Ichikawa, J.; Jyono, H.; Kudo, T.; Fujiwara, M.; Yokota, M. Synthesis
2005, 39 and references therein.
(17) Letsinger, L. R.; Gilpin, A. J.; Vulio, J. W. J. Org. Chem. 1962,
27, 673.
(18) Kanoh, S.; Muramoto, H.; Kobayashi, N.; Motoi, M.; Suda, H. Bull.
Chem. Soc. Jpn. 1987, 60, 3659.
(13) (a) Vettorazzi, N.; Fernandez, H.; Silber, J. J.; Sereno, L. Electro-
chim. Acta 1990, 35, 1081. (b) Mizoguchi, T.; Adams, R. N. J. Am. Chem.
Soc. 1962, 12, 178.
(14) (a) Xi, C.; Jiang, Y.; Yang, X. Tetrahedron Lett. 2005, 46, 3909.
(b) Jiang, Y.; Xi, C.; Yang, X. Synlett 2005, 1381.
(19) Jona, H.; Mandai, H.; Chavasiri, W.; Takeuchi, K.; Mukaiyama, T.
Bull. Chem. Soc. Jpn. 2002, 75, 291.
J. Org. Chem, Vol. 71, No. 17, 2006 6415

Saitoh et al.
SCHEME 2. Preparation of Cyclic Ethers 5 and 8
(Precursors of Dications 1 and 9)a
SCHEME 4. Oxidative Coupling of Enolate
SCHEME 5. Reoxidation of Acenaphthene 2a to Cyclic
Ether 5a (Precursor of Dications 1a and 1b)
SCHEME 6. Oxidative Coupling of Anilines 12
a Reagents and conditions: (a) n-BuLi (220 mol %), rt, 2 h/Et2O. (b)
Ar2CO (240 mol %), reflux, 4 h. (c) CF3CO2H (10 mol %), rt, 10 h/CH2Cl2.
(d) PhLi (500 mol %), -78 °C, 1 h/THF.
SCHEME 3. Synthesis of 6,6′-Dimethyl-1,1′-biphenyl-2,2′-
diylbis(diphenylmethylium) (9)
and 1b, after an aqueous workup was more practical. On
treatment with CAN or HClO4, 2a was transformed to 5a in
67% or 90% yield, respectively (Scheme 5). Acenaphthene 2a
can now be recycled, which makes the dication oxidants
practical.
(c) Synthesis of Benzidines. Oxidation of anilines with
dications 1 was then investigated. On treatment of N,N-diethyl-
3,5-dimethylaniline 12a (Eox ) 0.32 V vs Fc/Fc+) with a small
excess amount (60 mol %) of 1a or 1b, the reaction proceeded
smoothly even at -78 °C to give exclusively the desired para-
coupled bisaniline, N,N,N′,N′-tetraethylbenzidine 13a, in 98%
or 93% yield, respectively (Scheme 6; Table 2, entries 1 and
2). Dications 1 were quantitatively recovered as acenaphthene
2a, which indicates that 1a and 1b acted as a two-electron
oxidant in the coupling reaction of 12a.22 Dication 1c bearing
methoxy groups on the four benzene rings was less effective in
this reaction, giving 13a in 57% yield (entry 3), presumably
due to its lower oxidizing power.23 Dication 9 with a biphenyl
93% yield as dark red crystals (Table 1, entry 4). Dication 1b
(X ) OTf) was also prepared from 5a in quantitative yield on
treatment with Me3SiOTf instead of Me3SiClO4 under similar
conditions (entry 5).20 Me3SiBF4, Me3SiPF6, Me3SiSbF6, and
Me3SiReO4 gave no dications with the corresponding counter-
cation.
We also prepared dication 9 bearing a 1,1′-biphenyl-2,2′-diyl
backbone for comparison. In contrast to dications 1a and 1b, 9
was much more easily generated at room temperature for only
1 h on treatment of 8 with Me3SiClO4 in CH2Cl2 without HFIP
(Scheme 3).
-
backbone gave a complex mixture, and Ph3C+BF4 afforded
(b) Dications 1 as an Oxidizing Agent. We first examined
the oxidation behavior of dications 1 toward nucleophilic
substrates in the reaction with metal enolates as an example of
an anionic species. When the potassium enolate generated from
propiophenone (10) was treated with 60 mol % of 1a in the
presence of hexamethylphosphoric triamide (HMPA) at -78
°C, the expected self-coupling product 11, 2,3-dimethyl-1,4-
diphenylbutane-1,4-dione, was obtained in 65% yield (80% yield
based on the consumed 10, dl/meso ) 65/35).21 The addition
of the enolate to dication 1a was suppressed in contrast to trityl
cation, probably due to steric hindrance around the cations
(Scheme 4). Thus, dication 1a was found to act as an organic
one-electron-transfer oxidant even for nucleophilic substrates.
During the reaction, 1a was reduced to acenaphthene 2a via
C-C bond formation between the two carbocation centers.
While 2a regenerated 1a by reoxidation with HClO4 in HFIP,
isolation of cyclic ether 5a, a stable precursor of dications 1a
no coupling products, partly due to the nucleophilic attack of
12a on the cations (entries 4 and 5). These facts clearly suggest
that two methylium ions in close proximity are essential for
efficient oxidation.
Moreover, other oxidants such as 2,3-dichloro-5,6-dicy-
anobenzoquinone (DDQ), a triarylaminium radical cation [(4-
BrC6H4)3N+• SbCl6-], and Ce(NH4)2(NO3)6 (CAN), which are
widely used in organic synthesis, were also examined in the
coupling reaction. Treatment of 12a with DDQ or (4-
-
BrC6H4)3N+• SbCl6 gave no oxidation products or many side
products other than 13a, while 13a was obtained in 83% yield
with CAN at room temperature (entries 6-8). To investigate
the difference in reactivity between the dication 1a and other
oxidants such as CAN, FeCl3, PhI(OAc)2, and PhI(OCOCF3)2,
we examined the oxidative coupling of 3,5-dichloro-N,N-
(22) Electron-rich benzenes other than anilines, such as anisole and di-
and trimethoxybenzenes, gave no dimeric products on treatment with
dication 1a.
(23) The reduction peak potentials of dications 1 (Ar ) Ph and C6H4-
4-OMe) were reported to be 0.20 and -0.17 V vs Fc/Fc+, determined from
the cyclic voltammogram of 2a and 1c, respectively.8a,c
(20) The TfO- salt 1b is more moisture sensitive than 1a and has to be
handled and stored with care.
(21) Schmittel, M.; Burghart, A.; Malisch, W.; Reising, J.; So¨llner, R.
J. Org. Chem. 1998, 63, 396.
6416 J. Org. Chem., Vol. 71, No. 17, 2006

Bis(triarylmethylium) as Two-Electron Oxidant
TABLE 2. Oxidative Coupling of Aniline 12aa
SCHEME 7. Plausible Reaction Mechanism for the
Oxidative Coupling of 12
TABLE 4. Synthesis of Benzidines 13 from Aniline 12
a -78 °C, 1 h/CH2Cl2. b rt, 2 h/MeCN-H2O.
TABLE 3. Oxidative Coupling of Aniline 12ba
entry
oxidant
time/h
yield of 13b/%
1
1a
1
24
24
24
24
78
12
24
0
2b
3
CAN (120 mol %)
FeCl3 (120 mol %)
PhI(OAc)2
4
5
PhI(OCOCF3)2
7
a rt/CH2Cl2. b rt/MeCN-H2O.
diethylaniline (12b) (Eox ) 0.73 V vs Fc/Fc+), whose oxidation
potential is higher than that of 12a.24 The reaction of 12b with
1a was complete at room temperature in 1 h to afford 13b in
78% yield, whereas the other oxidants used here gave poor
results (Scheme 6, Table 3). Dication 1a proved far more
efficient as an oxidant to produce benzidine 13b from 12b.
A plausible reaction mechanism for the oxidative coupling
with 1 is shown in Scheme 7. Dication 1 oxidizes N,N-
dialkylaniline 12 to generate cation radical 14, which in turn
reacts with 12, leading to the coupled cation radical 15.
Deprotonation of 15 gives radical 16, which is further oxidized
to cation 17 with dication 1 or its one-electron reduced form.
Dimer 13 is finally produced after deprotonation of 17 and exists
in equilibrium with its ammonium salt. Overall, dication 1 is
transformed to acenaphthene 2 via two-electron reduction,
effected by two molar amounts of N,N′-dialkylaniline 12.
To expand the scope of the present oxidative coupling, several
other N,N-dialkylanilines were treated with 1a. As summarized
in Table 4, all of the coupling reactions occurred regioselectively
to afford the para-coupled dimer of N,N-dialkylanilines without
formation of ortho- and meta-coupled products. N,N-Dimethyl-
aniline 12c gave the corresponding benzidine 13c in 95% yield
without demethylation on the nitrogen atom, which has been
reported to occur in its oxidation.25 Furthermore, the self-
coupling proceeded successfully even when the aniline nitrogen
had removable protecting groups such as allyl or benzyl groups
a 2,6-Di-tert-butylpyridine (240 mol %) was added. 1a (120 mol %) was
employed.
(entries 3 and 4). However, the reactions of N-unsubstituted
and N-monoethylated anilines led to complex mixtures, and no
reaction was observed with N-acylated anilines. Dimers 13 were
obtained in high to excellent yield from 3,5-disubstituted and
3-halogenated N,N-dialkylanilines 12a-e, 12h, and 12i (entries
1-5, 8, and 9). Aniline 12j bearing an ethoxycarbonyl group
at the 3-position was transformed to the corresponding benzidine
without affecting the ester moiety (entry 10).
Because the oxidative coupling of N,N-diethylaniline 12k
resulted in 49% yield of 13k with 36% recovery of 12k, the
addition of base was examined to scavenge the eliminated
protons, which might protonate the starting aniline 12k and
retard its oxidation. While triethylamine and 2,6-lutidine were
(24) It was reported that the CuBr/H2O2 system did not promote the
coupling reaction of anilines bearing an electron-withdrawing group such
as chlorine on the aromatic ring.14b
(25) Hunter, D. H.; Barton, D. H. R.; Motherwell, W. J. Tetrahedron
Lett. 1984, 25, 603.
J. Org. Chem, Vol. 71, No. 17, 2006 6417

Saitoh et al.
SCHEME 8. Coupling of Proton Sponge with 1a
SCHEME 9. Synthesis of Phenanthridin-6(5H)-one 21 with
Dication 1aa
oxidized with 1a, 2,6-di-tert-butylpyridine promoted the cou-
pling reaction of 12k as expected. The addition of the base (240
mol %) and 120 mol % of dication 1a improved the yield of
13k to 66%. In addition, a diamine substrate, N,N,N′,N′-
tetramethyl-1,8-diaminonaphthalene (18, Proton Sponge), was
also subjected to the reaction to give the coupling product 19
at the 4-position in 77% yield (Scheme 8).
a The reaction was carried out in 0.01 M.
3,5-Disubstituted or 3-substituted anilines generally afforded
better yields of benzidines, compared with the other anilines.
This fact was explained by the overoxidation of the products.
Two-electron oxidation of the produced dimers 13 gave rise to
the formation of diiminium salts 15, which led to a decrease in
yield of 13. Benzidines 13 having substituents at the 2,2′,6,6′-
positions were less easily oxidized to give 15 than nonsubstituted
and 3,3′-disubstituted benzidines, because steric inhibition of
resonance decreased the stability of the intermediary radical
cations 14 and diiminium salts 15 (Figure 1). This effect was
confirmed with cyclic voltammetry measurements: whereas the
oxidation potential of 14a (Eox ) 0.46 V vs Fc/Fc+) was higher
than that of aniline 12a (Eox ) 0.32 V vs Fc/Fc+), that of 14c
(Eox ) 0.36 V vs Fc/Fc+) was lower than that of aniline 12c
(Eox ) 0.77 V vs Fc/Fc+).
As an application of the oxidative benzidine synthesis, we
also tried to construct a phenanthridin-6(5H)-one skeleton, which
is found in poly(ADP-ribose) polymerase-l (PARP 1) inhibi-
tors.26 When the intramolecular coupling of amide 20 was
attempted with 120 mol % of 1a under high dilution conditions
(0.01 M in CH2Cl2), the desired phenanthridinone 21 was
obtained in 46% yield. To drive the reaction to completion, the
addition of 2,6-di-tert-butylpyridine (240 mol %) with 180 mol
% of 1a was examined (vide supra). Thus, the reaction
proceeded cleanly to improve the yield of 21 to 76% (Scheme
9).
via deoxygenation on treatment with a silylating agent in HFIP.
The oxidative coupling of N,N-dialkylanilines has been suc-
cessfully achieved by the use of 1a or 1b to provide facile access
to a variety of benzidine derivatives including a phenanthridin-
6(5H)-one. These results have clearly revealed that the salts of
dication 1 (Ar ) Ph) function as organic reagents for electron-
transfer oxidation involving two electrons.
Experimental Section
1,1,3,3-Tetraphenyl-1H,3H-benzo[d,e]isochromene (5a).17 To
a solution of 1,8-dibromonaphthalene (2.0 g, 7.0 mmol) in Et2O
(35 mL) was added n-BuLi (6.6 mL, 2.60 M in hexane, 17.2 mmol)
at 0 °C under argon. The reaction mixture was stirred at room
temperature for 2 h, and then benzophenone (3.1 g, 17.0 mmol)
was added. After heating at reflux for 5 h, the reaction was quenched
with saturated aqueous NH4Cl. Organic materials were extracted
with EtOAc three times. The combined extracts were washed with
brine and dried over Na2SO4. After removal of the solvent under
reduced pressure, the residue was dissolved in CH2Cl2 (10 mL),
and a catalytic amount of trifluoroacetic acid (0.05 mL, 0.7 mmol)
was added at room temperature. The reaction mixture was stirred
for 10 h, and then MeOH (20 mL) was added. After the solution
was stirred at room temperature for 1 h, the resulting precipitate
was collected by filtration, washed with MeOH, and dried under
reduced pressure to give 5a (2.7 g, 80%) as white crystals. Mp
1
244-245 °C (CH2Cl2-MeOH). H NMR (400 MHz, CDCl3) δ
6.95-7.15 (22H, m), 7.37 (2H, dd, J ) 8.0, 7.2 Hz), 7.80 (2H, d,
J ) 8.0 Hz). 13C NMR (100 MHz, CDCl3) δ 84.3, 124.9, 126.4,
126.5, 126.6, 126.7, 127.0, 129.5, 132.9, 136.1, 146.5. IR (KBr)
1578, 1546, 1452, 1359, 1087, 704, 623 cm-1. FAB HRMS calcd
for C36H27O 475.2062 (M + 1), found 475.2067.
Conclusion
Naphthalene-1,8-diylbis(diphenylmethylium) salts 1a and 1b
were easily prepared from the corresponding cyclic ether 5a
FIGURE 1. Cyclic voltammetry analysis [Eox (Ered) vs Fc/Fc+] and conformation analysis (DFT calculations were perforned with B3LYP/6-31G*)
of 13a,c-15a,c.
6418 J. Org. Chem., Vol. 71, No. 17, 2006

Bis(triarylmethylium) as Two-Electron Oxidant
Trimethylsilyl Perchlorate (Me3SiClO4 toluene solution). To
a solution of AgClO4 (4.6 g, 22 mmol) in toluene (30 mL) was
added trimethylsilyl chloride (2.8 mL, 22 mmol) under argon. After
this mixture was stirred at room temperature for 0.5 h and then
left standing for 0.5 h without stirring, the supernatant was used as
a reagent (Me3SiClO4, 0.74 M in toluene) for the preparation of
the dications.
(5.0 mL) at 0 °C under argon. After stirring for 12 h, the reaction
was quenched with water. Organic materials were extracted with
EtOAc three times. The combined extracts were washed with brine
and dried over Na2SO4. After removal of the solvent under reduced
pressure, EtOH (20 mL) was added to the residue. To the resulting
suspension were added 10% Pd/C (2.18 g, 2.1 mmol) and aqueous
HCl (2.5 mL, 10 M, 25 mmol). After the reaction mixture was
stirred under H2 for 2 d, aqueous NaHCO3 was added. Organic
materials were extracted with EtOAc three times. The combined
extracts were washed with brine and dried over Na2SO4. After
removal of the solvent under reduced pressure, the residue and
iodomethane (4.5 mL, 72 mmol) were successively added to a
suspension of NaH (3.08 g, 60% dispersion in mineral oil, 77 mmol)
in THF (10 mL) at 0 °C under argon. After being stirred at 50 °C
for 20 h, the reaction was quenched with water. Organic materials
were extracted with EtOAc three times. The combined extracts were
washed with brine and dried over Na2SO4. After removal of the
solvent under reduced pressure, the residue was purified by column
chromatography (hexanes-EtOAc 5:1) to give 20 (0.72 g, 22%)
as pale yellow crystals. Mp 98-99 °C (EtOH). 1H NMR (400 MHz,
CDCl3) δ 2.80 (6H, s), 2.80 (6H, s), 3.48 (3H, s), 6.35 (1H, dd, J
) 2.5, 2.5 Hz), 6.43 (1H, dd, J ) 8.2, 1.2 Hz), 6.48 (1H, dd, J )
8.2, 2.5 Hz), 6.60 (1H, dd, J ) 8.2, 2.5 Hz), 6.67 (1H, d, J ) 8.2
Hz), 6.74-6.75 (1H, m), 7.00 (1H, dd, J ) 8.2, 8.2 Hz), 7.06 (1H,
dd, J ) 8.2, 8.2 Hz). 13C NMR (100 MHz, CDCl3) δ 38.4, 40.5,
40.6, 110.4, 111.4, 113.1, 113.7, 114.6, 117.0, 128.1, 129.3, 136.7,
146.0, 149.8, 151.0, 171.2. IR (neat) 2883, 2802, 1637, 1595, 1570,
1496, 1433, 1344, 1284, 1227, 1107, 993, 839, 771 cm-1. Anal.
Calcd for C18H23N3O: C, 72.70; H, 7.80; N, 14.13. Found: C,
72.55; H, 7.80; N, 13.97.
Naphthalene-1,8-diylbis(diphenylmethylium) Diperchlorate
(1a). To a stirred solution of 5a (2.0 g, 4.2 mmol) in 1,1,1,3,3,3-
hexafluoro-2-propanol (HFIP, 30 mL) was added Me3SiClO4 (17.1
mL, 0.74 M in toluene, 12.6 mmol) at room temperature under
argon, and the mixture was stirred at the same temperature for 2 d.
The solvent was removed under reduced pressure, and the crude
product was dissolved in CH2Cl2 (3.0 mL) and Et2O (10 mL). After
the mixture was stirred at room temperature for 1 h, the resulting
black precipitate was collected by filtration, washed with Et2O (10
mL) and then CH2Cl2 (3.0 mL) under argon, and dried under
reduced pressure to give 1a (2.6 g, 95%) as dark red crystals. Mp
170 °C dec (Et2O-CH2Cl2-HFIP). 1H NMR (400 MHz, CD3CN)
δ 6.54 (2H, br s), 6.73 (2H, br s), 7.37 (2H, br s), 7.41-7.65 (10H,
m), 7.75 (2H, br s), 7.98 (2H, br s), 8.05 (2H, dd, J ) 7.6, 7.6 Hz),
8.23 (2H, br s), 8.95 (2H, dd, J ) 8.4, 1.6 Hz). 13C NMR (100
MHz, CD3CN) δ 127.7, 128.0, 129.7, 130.1, 131.9, 136.6, 137.5,
139.7, 144.8, 151.0, 207.6. IR (KBr) 1489, 1444, 1217, 1184, 1018,
742, 694 cm-1. Crystal data: C36H26Cl2O8, M ) 657.47, mono-
clinic, a ) 16.090(7) Å, b ) 10.544(4) Å, c ) 17.881(7) Å, U )
2936(2) Å3, T ) 120(2) K, space group P21/a, Z ) 4, µ(Mo KR)
) 0.279 mm-1, 16 652 reflections measured, 5037 unique (Rint
)
0.0296) which were used in all calculations. The final wR(F2) was
0.1467 (all data). The largest residual electron density hole was
-0.773 e‚Å-3
.
3,8-Bis(dimethylamino)-5-methylphenanthridin-6(5H)-one (21).
To a solution of 20 (35.0 mg, 0.12 mmol) and 2,6-di-tert-
butylpyridine (54.1 mg, 0.28 mmol) in CH2Cl2 (10 mL) was added
1a (141 mg, 0.21 mmol) at -78 °C under argon. The reaction
mixture was stirred at the same temperature for 1 h. After
completion of the oxidative coupling (TLC monitoring), the reaction
was quenched with saturated aqueous NaHCO3. Organic materials
were extracted with EtOAc three times, and the combined extracts
were washed with brine and dried over Na2SO4. After removal of
the solvent under reduced pressure, the residue was purified by
PTLC (hexanes-EtOAc 1:1) to give 21 (26.5 mg, 76%) as a pale
yellow solid. Mp 209-210 °C (EtOH). 1H NMR (500 MHz, CDCl3)
δ 3.06 (12H, s), 3.79 (3H, s), 6.53 (1H, s), 6.72 (1H, d, J ) 7.4
Hz), 7.18 (1H, dd, J ) 8.9, 2.4 Hz), 7.72 (1H, s), 7.97-8.00 (2H,
m). 13C NMR (125 MHz, CDCl3) δ 29.9, 40.6, 40.7, 97.5, 108.1,
109.6, 109.9, 118.7, 121.8, 122.9, 124.2, 124.5, 137.8, 148.8, 150.1,
162.5. IR (neat) 2999, 2891, 2800, 1635, 1604, 1498, 1435, 1363,
Procedure for the Transformation of Acenaphthene 2a to
Cyclic Ether 5a. To a solution of 2a (32.9 mg, 0.072 mmol) in
CH2Cl2 (2.0 mL) was added HClO4 (1.7 mL, 0.42 M in toluene,
0.72 mmol: see the Supporting Information) at room temperature
under argon. After stirring for 4 d, the reaction was quenched with
saturated aqueous NaHCO3. Organic materials were extracted with
EtOAc three times, and the combined extracts were washed with
brine and dried over Na2SO4. After removal of the solvent under
reduced pressure, the residue was purified by PTLC (toluene-
hexane-CHCl3 1:3:2) to give 5a (31.9 mg, 90%).
N,N,N′,N′-Tetraethyl-2,2′,6,6′-tetramethylbenzidine (13a). To
a solution of 12a (27.5 mg, 0.16 mmol) in CH2Cl2 (2.0 mL) was
added 1a (61.8 mg, 0.10 mmol) at -78 °C. The reaction mixture
was stirred at the same temperature for 1 h. After completion of
the oxidative coupling (TLC monitoring), the reaction was quenched
with saturated aqueous NaHCO3. Organic materials were extracted
with EtOAc three times and the combined extracts were washed
with brine and dried over Na2SO4. After removal of the solvent
under reduced pressure, the residue was purified by PTLC (toluene-
hexane-CHCl3 1:3:2) to give 13a (26.7 mg, 98%) as white crystals
along with acenaphthene 2a (42.8 mg, 99%). Mp 119-120 °C
(EtOH). 1H NMR (400 MHz, CDCl3) δ 1.18 (12H, t, J ) 6.8 Hz),
1.87 (12H, s), 3.34 (8H, q, J ) 6.8 Hz), 6.45 (4H, s). 13C NMR
(100 MHz, CDCl3) δ 12.9, 20.8, 44.2, 111.0, 128.3, 137.0, 146.4.
IR (neat) 2964, 1601, 1473, 1373, 1286, 1198, 825 cm-1. Anal.
Calcd for C24H36N2: C, 81.76; H, 10.29; N, 7.95. Found: C, 81.50;
H, 10.31; N, 7.69.
1321, 1234, 1105, 1063, 1005, 958, 904, 870, 804, 742, 667 cm-1
.
FAB HRMS calcd for C18H22N3O 296.1763 (M + 1), found
296.1745.
Acknowledgment. We are grateful to Central Glass Co.,
Ltd., for a generous gift of HFIP. We thank Dr. N. Kanoh (the
University of Tokyo) for the X-ray crystal structure analysis of
compound 1a. This work was supported by the Grant-in-Aid
for the 21st century COE program for Frontiers in Fundamental
Chemistry from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
3-(Dimethylamino)-N-[3-(dimethylamino)phenyl]-N-methyl-
benzamide (20). To a solution of 3-nitroaniline (1.80 g, 13 mmol)
and triethylamine (2.5 mL, 18 mmol) in CH2Cl2 (5.0 mL) was added
a solution of 3-nitrobenzoyl chloride (2.00 g, 11 mmol) in CH2Cl2
Supporting Information Available: Experimental procedures
and spectroscopic data of compounds 5b, 1b, 1c, 8, 9, 11, 12a-m,
2a, 13b-m, and 19; X-ray data of compound 1a; copies of 13C
spectra of compounds 2a, 5a, 5b, 13c, 13d, 13f, 13g, 13j, 13l, 13m,
and 21. This material is available free of charge via the Internet at
http://pubs.acs.org.
(26) Li, J.-H.; Serdyuk, L.; Rerraris, D. V.; Xiao, G.; Tays, K. L.; Kletzly,
P. W.; Li, W.; Lautar, S.; Zhang, J.; Kalish, V. J. Bioorg. Med. Chem. Lett.
2001, 11, 1687 and references therein.
JO060662S
J. Org. Chem, Vol. 71, No. 17, 2006 6419