An alternative synthesis of benzobis(imidazolium) salts via a 'one-pot' cyclization/oxidation reaction sequence

Article abstract of DOI:10.1016/j.tetlet.2006.05.076

Cyclization of N-aryl and N-alkyl 2,5-diamino-1,4-benzoquinonediimines using paraformaldehyde under acidic conditions followed by oxidation with catalytic amounts of Pd(OAc)₂ afforded their respective benzobis(imidazolium) salts in yields of 48

Full text of DOI:10.1016/j.tetlet.2006.05.076

Tetrahedron Letters 47 (2006) 5123–5125
An alternative synthesis of benzobis(imidazolium) salts via a
‘one-pot’ cyclization/oxidation reaction sequence
Andrew J. Boydston, Dimitri M. Khramov and Christopher W. Bielawski*
Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, TX 78712, United States
Received 2 April 2006; revised 10 May 2006; accepted 12 May 2006
Available online 6 June 2006
Abstract—Cyclization of N-aryl and N-alkyl 2,5-diamino-1,4-benzoquinonediimines using paraformaldehyde under acidic condi-
tions followed by oxidation with catalytic amounts of Pd(OAc)2 afforded their respective benzobis(imidazolium) salts in yields of
48–98%. A comparative solid-state study between a 2,5-diamino-1,4-benzoquinonediimine and its corresponding benzobis(imidazo-
lium) dichloride was also performed.
ꢀ 2006 Elsevier Ltd. All rights reserved.
We have recently reported a concise synthesis of a series
RHN
RN
NR
RHN
RHN
NR
NR
of 1,2,4,5-tetrakis(N-alkyl and N-arylamino)benzenes1
and demonstrated that they undergo formylative cycli-
zation with triethylorthoformate to afford their respec-
tive benzobis(imidazolium) salts.2 The electron-rich
tetraaminobenzene intermediates were found to oxidize
under aerobic conditions which necessitated the use of
inert atmosphere or drybox techniques for their isola-
tion and storage. In contrast, their oxidized products,
namely azophenines3 and related 2,5-diamino-1,4-benzo-
quinonediimines,4 are robust and accessible via
numerous synthetic protocols.3–5 These quinone deriva-
tives have found tremendous utility in coordination
chemistry,6 as pH-dependent chromophores,7 and in
theoretical studies.8 In an effort to build upon our previ-
ous work and encompass new methodologies for prepar-
ing benzobis(imidazolium) salts using simple, bench-top
procedures, we envisioned that azophenines and 2,5-di-
amino-1,4-benzoquinonediimines could function as a
highly versatile class of appropriate starting materials.
NHR
vic-diamine vic-diimine
1-o
1-p
R
N
X
CH2O
NR
n
n
HX
N
R
3
R
NR
2
[O]
CH2O
HX
NHR
N
H
H
N
NHR
R
5
4
Scheme 1. The o-tautomer of 2,5-diamino-1,4-benzoquinonediimine
(1-o) exhibits vicinal diamino and diimino fragments which are
independently known for undergoing dehydrative cyclizations with
paraformaldehyde.
As shown in Scheme 1, the ortho-quinoid tautomer9
(1-o) of 2,5-diamino-1,4-benzoquinonediimine 1 displays
vicinal diamino and diimino moieties which are inde-
pendently known for undergoing dehydrative cycliza-
tions. For example, treatment of 1,2-diimine 2 with
paraformaldehyde affords imidazolium salt 310 whereas
the corresponding vicinal diamine 4 affords the cyclic
N,N0-acetal 5.11 With these considerations in mind, we
suspected analogous cyclization reactions with 1 should
afford an annulated benzimidazolium/N,N0-acetal
hybrid.12 Oxidation of this intermediate using Thorn’s
recently reported13 Pd-mediated process for efficiently
generating hydrogen gas from phenylene diamine-
derived N,N0-acetals should then afford the respective
benzobis(imidazolium) salts. Furthermore, the apparent
compatibility of the cyclization and oxidation reaction
conditions suggested they could be performed succes-
sively in a single reaction vessel.
*
Corresponding author. Tel.: +1 512 232 3839; fax: +1 512 471
8696; e-mail: bielawski@cm.utexas.edu
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.05.076

5124
A. J. Boydston et al. / Tetrahedron Letters 47 (2006) 5123–5125
Cl
R
R
RHN
RN
NR
CH2O
N
N
H
H
n
N
R
N
R
HCl, PhCH3
110 ºC
NHR
1a - 1e
6
C2
C3
2 Cl
R
N
7a, 48% (R = Ph)
7b, 98% (R = 2-MeOPh)
7c, 85% (R = t-Bu)
7d, 95% (R = Ad)
R
N
N1
C4
Pd(OAc)2
C1
N2
i
-PrOH, PhCH3
N
R
N
R
7e, 93% (R = 2,5-di-t-BuPh)
50 ºC
Scheme 2. Conversion of 2,5-diamino-1,4-quinonediimines to their
respective benzobis(imidazolium) salts using a ‘one-pot’ cyclization/
oxidation reaction sequence.
To test this hypothesis, azophenine 1a was obtained via
condensation of aniline with o-benzoquinone dioxime
according to literature protocol.5a Related 2,5-diamino-
1,4-quinonediimines 1b–e were prepared via Pd-cata-
lyzed aryl amination14 of 1,2,4,5-tetrabromobenzene fol-
lowed by an aerobic workup,15 in analogy with our
previously reported procedure. Confirmation of the
2,5-diamino-1,4-quinonediimine structure was deter-
mined through identification of the diagnostic chemical
shift of the vinylic proton of the quinoid ring (d =
5.5 ppm in CDCl3) and single crystal X-ray analysis
for 1b.16 As shown in Scheme 2, compounds 1 were each
reacted with paraformaldehyde in PhCH3 under acidic
conditions at 110 ꢁC.17 Within 2–6 h, the intense colors
associated with these quinone derivatives had dissipated
and the reaction mixtures developed yellow-brown
solids suggesting that a hybrid intermediate 6 had
formed.18 The reaction temperature was then reduced
to 50 ꢁC and, to facilitate dissolution of solids, i-PrOH
(10% by volume) was added. Upon the addition of
catalytic amounts of Pd(OAc)2 (1 mol %), slow and
persistent generation of gas was observed. Analysis of
Figure 1. ORTEP drawing of 7b (counterions have been removed for
˚
clarity). Selected bond lengths (A) and angles (ꢁ): N1–C1, 1.3352(19);
N2–C1, 1.3398(19); N1–C2, 1.4007(18); N2–C3, 1.3986(18); C2–C3,
1.4062(19); C2–C4, 1.384(2); N1–C1–N2, 110.21(13); C1–N1–C2,
108.55(11); N1–C2–C3, 106.37(12); C4–C2–N1, 130.60(13); C6–C5–
N1–C2, 126.27(15); C3–N2–C12–C13, 59.12(19).
In summary, we have developed an alternative, ‘one-pot’
protocol for synthesizing a variety of benzobis(imidazo-
lium) salts from readily available 2,5-diamino-1,4-
benzoquinonediimines. In particular, the o-quinoid
tautomers of 2,5-diamino-1,4-benzoquinonediimines
were cyclized using paraformaldehyde to obtain benz-
imidazolium/N,N0-acetal hybrid intermediates which
were subsequently oxidized to afford their respective
bis(azolium) salts.
Acknowledgments
We are grateful to the US Army Research Office
(W911NF-05-1-0430) and UT-Austin for generously
supporting this work. A.J.B. thanks UT-Austin for a
Continuing Graduate Fellowship.
1
the crude reaction mixtures by H NMR spectroscopy
indicated the 2,5-diamino-1,4-benzoquinonediimines
were cleanly converted to the desired benzobis(imidazo-
lium) products (diagnostic signal: C–H, d = 9–11
ppm in DMSO-d6) 7 in good to excellent yields (48–
98%).19
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.05.076.
1
Although H NMR analyses of the products obtained
above were strongly indicative of the desired benzo-
bis(imidazolium) structure, they were further character-
ized by using X-ray analysis after quality crystals of
benzobis(imidazolium) dichloride 7b were obtained by
slow cooling of a hot, saturated, DMSO solution.16 As
shown in Figure 1, the N1–C2–N2 bond angle (110.2ꢁ)
was typical of annulated imidazolium compounds as
were the imidazole bond lengths.20 Furthermore, C–C
bond lengths typical of arene rings were observed
References and notes
1. Khramov, D. M.; Boydston, A. J.; Bielawski, C. W. Org.
Lett. 2006, 8, 1831.
2. (a) Boydston, A. J.; Williams, K. A.; Bielawski, C. W.
J. Am. Chem. Soc. 2005, 127, 12496; (b) Kamplain, J. W.;
Bielawski, C. W. Chem. Commun. 2006, 1727.
˚
(1.38–1.41 A) in the tetraaminoarene fragment, which
3. Azophenine generally refers to N,N0,N00,N000-tetraphenyl-
2,5-diamino-1,4-benzoquinonediimine; see: (a) Fischer, O.;
Hepp, E. Ber. Dtsch. Chem. Ges. 1888, 21, 676; (b)
Kimich, C. Ber. Dtsch. Chem. Ges. 1875, 8, 1026.
4. (a) Siri, O.; Braunstein, P. Chem. Commun. 2000, 2223; (b)
Masui, H.; Freda, A. L.; Zerner, M. C.; Lever, A. B. P.
Inorg. Chem. 2000, 39, 141.
indicated the parent quinone core was successfully
reduced. The N-anisidyl rings were rotated out-of-plane
with respect to the benzobis(imidazolium) core (dihedral
angles ranged between 35ꢁ and 60ꢁ) suggesting that there
was relatively minimal electronic overlap between the
two moieties.

A. J. Boydston et al. / Tetrahedron Letters 47 (2006) 5123–5125
5125
5. (a) Paetzold, F.; Niclas, H. J.; Foerster, H. J. J. Prakt.
Chem. 1986, 328, 5; (b) Adams, R.; Schowalter, K. A.
J. Am. Chem. Soc. 1952, 74, 2597; (c) Ruggli, P.;
Buchmeier, F. Helv. Chim. Acta 1945, 28, 850.
672.5134. Azophenine 1e: 1H NMR (CDCl3): d 8.13 (s,
2H), 7.03 (s, 2H), 6.78 (br, 8H), 6.31 (s, 2H), 1.17 (s, 72H);
13C NMR (CDCl3): d 151.4, 117.6, 90.7, 34.8, 31.4; HRMS:
[M+1]+ calcd for C62H88N4, 889.7009. Found: 889.7089.
16. Crystal data for 1b: C34H32N4O4–2C4H8O, M = 704.84,
triclinic, P1, a = 12.5090(8), b = 13.3300(9), c =
´ ˇ
6. (a) Frantz, S.; Rall, J.; Hartenback, I.; Scheid, T.; Zalis, S.;
Kaim, W. Chem. Eur. J. 2004, 10, 149; (b) Siri, O.;
Braunstein, P. Chem. Commun. 2002, 208; (c) Rall, J.;
˚
14.2730(11) A, a = 64.179(3), b = 89.750(4), c = 64.058(5)ꢁ,
3
V = 1874.8(2) A , Z = 2, Dc = 1.249 g cmꢀ3, l = 0.084
˚
Stange, A. F.; Hubler, K.; Kaim, W. Angew. Chem., Int.
¨
mmꢀ1, F(000) = 752, k (Mo Ka) = 0.71073 A, large red
˚
Ed. 1998, 37, 2681.
7. (a) Elhabiri, M.; Siri, O.; Sornosa-Tent, A.; Albrecht-
Gary, A.-M.; Braunstein, P. Chem. Eur. J. 2004, 10, 134;
prisms, crystal size 0.33 · 0.30 · 0.25 mm, 10820 reflections
measured (Rint = 0.0499), 6570 unique, R1 = 0.1268 for
I > 2r(I) and 0.2564 for all data. There were two molecules
of THF in the asymmetric unit, one of which was found to
be disordered and could not be adequately modeled. Key
bond lengths (A) and angles (ꢁ): N1–C1, 1.301(5); N2–C2,
1.376(5); C1–C2, 1.493(6); C1–C3, 1.431(6); C2–C3,
1.340(6); C4–N1–C1–C2, 176.1(4). Crystal data for 7b:
(C36H32N4O4) 2Cl–4C2H6SO, M = 968.07, triclinic, P1,
´
(b) Siri, O.; Braunstein, P.; Rohmer, M.-M.; Benard, M.;
Welter, R. J. Am. Chem. Soc. 2003, 125, 13793; (c) Rumpel,
H.; Limbach, H.-H. J. Am. Chem. Soc. 1989, 111, 5429.
8. Haas, Y.; Zilberg, S. J. Am. Chem. Soc. 2004, 126, 8991.
9. The equilibrium between the ortho- and para-quinoid
tautomers has been previously shown to favor the latter.6
10. (a) Yamashita, M.; Goto, K.; Kawashima, T. J. Am.
Chem. Soc. 2005, 127, 7294; (b) Bo¨hler, C.; Stein, D.;
˚
˚
a = 8.2689(2), b = 11.4843(2), c = 13.3347(3) A, a =
3
˚
Donati, N.; Grutzmacher, H. New J. Chem. 2002, 26,
112.090(1), b = 96.690(1), c = 90.029(1)ꢁ, V = 1164.00(4) A ,
¨
1291; (c) Niehus, M.; Erker, G.; Kehr, G.; Schwab, P.;
Fro¨hlich, R.; Blacque, O.; Berke, H. Organometallics 2002,
21, 2905; (d) Jafarpour, L.; Stevens, E. D.; Nolan, S. P.
J. Organomet. Chem. 2000, 606, 49.
Z = 1, Dc = 1.381 g cmꢀ3, l = 0.375 mmꢀ1, F(000) = 510, k
˚
(Mo Ka) = 0.71073 A, colorless prisms, crystal size
0.49 · 0.31 · 0.20 mm, 7435 reflections measured (Rint
=
0.0162), 5229 unique, R1 = 0.0363 for I > 2r(I) and 0.0460
for all data. The data were collected at 153(2) K using an
Oxford Cryostream low temperature device. The struc-
tures were solved by direct methods and refined by full-
matrix least-squares on F2 with anisotropic displacement
parameters for the non-H atoms using SHELXL-97 (Sheld-
rick, G. M. University of Gottingen, Germany, 1994).
Data for these structures have been deposited with the
Cambridge Crystallographic Data Centre (12 Union
Road, Cambridge CB2 1EZ, UK) as CCDC 603509 (1b)
and 603510 (7b).
11. (a) Donia, R. A.; Shotton, J. A.; Bentz, L. O.; Smith, G. E.
P. J. Org. Chem. 1949, 14, 952; (b) Bildstein, B.; Malaun,
M.; Kopacka, H.; Wurst, K.; Mitterbock, M.; Ongania,
K.-H.; Opromolla, G.; Zanello, P. Organometallics 1999,
18, 4325.
12. Attempts at direct conversion of 2,5-diamino-1,4-benzo-
quinonediimines to their respective benzobis(imidazolium)
salts using mixtures of electrophiles (e.g., equimolar
amounts of HC(OEt)3 and paraformaldehyde under
equilibrating conditions) were met with limited success.
13. Schwarz, D. E.; Cameron, T. M.; Hay, P. J.; Scott, B. L.;
Tumas, W.; Thorn, D. L. Chem. Commun. 2005, 5919; For
a related example, see: Montgrain, F.; Ramos, S. M.;
Wuest, J. D. J. Org. Chem. 1988, 53, 1489.
17. General procedure for preparing compounds 7: A 50 mL
flask was charged 1 (0.5 mmol), PhCH3 (20 mL), parafor-
maldehyde (1.2 mmol), and concd HCl (1 drop). After
stirring the mixture at 110 ꢁC for 2–6 h, the temperature
was reduced to 50 ꢁC and i-PrOH (2 mL) was added to
facilitate partial dissolution of solids. Pd(OAc)2 (5 lmol)
was then added and slow evolution of gas followed. The
mixture was stirred for an additional 2–4 h and then
concentrated to afford crude product. Note: this protocol
was found to work equally well in other solvents (e.g.,
CH3CN, DMF, DMSO, and EtOH). Spectral data of 7a–d
were in accord with their previously reported values.1
Characterization data for 7e: 1H NMR (CDCl3): d 9.98
(br, 2H), 7.97 (br, 8H), 7.82 (br, 2H), 7.62 (s, 4H), 1.32 (s,
72H); 13C NMR (CDCl3): d 154.0, 144.7, 132.1, 125.5,
120.7, 114.9, 99.6, 35.5, 31.4; HRMS: [M]+ calcd for
C64H88N4, 912.7009. Found: 912.6983.
14. (a) Wenderski, T.; Light, K. M.; Ogrin, D.; Bott, S. G.;
Harlan, C. J. Tetrahedron Lett. 2004, 45, 6851; (b) Hillier,
A. C.; Grasa, G. A.; Viciu, M. S.; Lee, H. M.; Yang, C.;
Nolan, S. P. J. Organomet. Chem. 2002, 653, 69; (c) Prim,
D.; Campagne, J.-M.; Joseph, D.; Andrioletti, B. Tetra-
hedron 2002, 58, 2041; (d) Hartwig, J. F. Angew. Chem., Int.
Ed. 1998, 37, 2046; (e) Wolfe, J. P.; Wagaw, S.; Marcox,
J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805.
15. General procedure for preparing compounds 1b–e: A
20 mL vial charged with 1,3-bis(2,6-diisopropylphenyl)-
imidazolium chloride (0.02 mmol), NaOt-Bu (0.02 mmol),
Pd(OAc)2 (0.01 mmol), and PhCH3 (5 mL). After
stirring the resulting mixture for 10 min, 1,2,4,5-tetra-
bromobenzene (1.00 mmol), amine (4.10 mmol), NaOt-Bu
(4.20 mmol), and PhCH3 (5 mL) were added. The resulting
mixture was sealed under an atmosphere of nitrogen and
stirred at 110 ꢁC for 8 h. After cooling to ambient
temperature, the resulting mixture was diluted with
hexanes and precipitated solids were collected by filtration.
Residual inorganic salts were removed by filtering CHCl3
solutions of the products. Characterization data for new
compounds: Azophenine 1b: 1H NMR (CDCl3): d 8.55 (s,
2H), 7.05–6.91 (m, 16H), 6.16 (s, 2H) 3.83 (s, 12H); 13C
NMR (CDCl3): d 150.4, 148.2, 134.4, 130.5, 121.0, 120.6,
119.1, 114.4, 111.3, 110.3, 93.1, 55.7, 55.5; HRMS: [M]+
calcd for C34H32N4O4, 560.2424. Found: 560.2428. Spec-
tral data of 1c was consistent with its previously reported1
18. Subjecting N,N0,N00,N000-tetra(p-chlorophenyl)-2,5-diamino-
1,4-benzoquinonediimine5a to the cyclization–oxidation
reaction sequence outlined in Scheme 2 afforded 1,3-
di(p-chlorophenyl)-5,6-di(p-chlorophenyl-amino)benzimid-
1
azolium chloride (95% yield): H NMR (CDCl3): d 10.14
(s, 1H), 7.97 (d, J = 9.2 Hz, 4H), 7.84 (d, J = 9.2 Hz, 4H),
7.49 (s, 8H), 7.13 (s, 2H), 5.95 (s, 2H).
19. It was also found that benzobis(imidazolium) salts 7 could
be prepared via a one-pot, reduction–cyclization reaction
sequence: Subjecting 1a–d independently to standard
hydrogenative conditions (10% Pd/C, 400 PSI H2) in
HC(OEt)3 for 16–24 h followed by addition of acid (HCl
or HBF4) at 60–110 ꢁC for 2–24 h afforded the respective
benzobis(imidazolium) salts 7a–d in 51–92% yields.
20. (a) Saravanakumar, S.; Oprea, A. I.; Kindermann, M. K.;
Jones, P. G.; Heinicke, J. Chem. Eur. J. 2006, 12, 3143; (b)
Hahn, F. E.; Jahnke, M. C.; Gomez-Benitez, V.; Morales-
Morales, D.; Pape, T. Organometallics 2005, 24, 6458.
1
value. Compound 1d: H NMR (CDCl3): d 6.69 (br, 2H),
5.77 (s, 2H), 2.10 (br, 12H), 1.97 (br, 24H), 1.68 (br, 24H);
13C NMR (CDCl3): d (ca 138), 92.2, 52.7, 42.6, 36.9, 29.8;
HRMS: [M]+ calcd for C46H64N4, 672.5131. Found: