Triphenylphosphine-mediated reductive cyclization of 2-nitrobiphenyls: A practical and convenient synthesis of carbazoles

Article abstract of DOI:10.1021/jo0503299

The synthesis of a series of substituted carbazoles from the corresponding 2-nitrobiphenyl derivatives using a novel modification of the Cadogan reaction is described. Cyclization of the 2-nitrobiphenyls was achieved via reductive deoxygenation of the nitro groups using a slight excess of triphenylphosphine in a suitable solvent. We have observed a temperature dependence on the extent of conversion under these conditions, with higher boiling solvents affording higher yields across a range of substrates. The new reaction conditions are very straightforward and convenient to execute, tolerate a broad range of functional groups, and yield carbazole products in the absence of unwanted side products.

Full text of DOI:10.1021/jo0503299

Triphenylphosphine-Mediated Reductive Cyclization of
2-Nitrobiphenyls: A Practical and Convenient Synthesis of
Carbazoles
Adam W. Freeman,* Marie Urvoy, and Megan E. Criswell
Eastman Kodak Company, Research and Development Laboratories, 1999 Lake Avenue,
Rochester, New York 14650-2116
adam.freeman@kodak.com
Received February 21, 2005
The synthesis of a series of substituted carbazoles from the corresponding 2-nitrobiphenyl derivatives
using a novel modification of the Cadogan reaction is described. Cyclization of the 2-nitrobiphenyls
was achieved via reductive deoxygenation of the nitro groups using a slight excess of triphenylphos-
phine in a suitable solvent. We have observed a temperature dependence on the extent of conversion
under these conditions, with higher boiling solvents affording higher yields across a range of
substrates. The new reaction conditions are very straightforward and convenient to execute, tolerate
a broad range of functional groups, and yield carbazole products in the absence of unwanted side
products.
Introduction
By virtue of their widespread occurrence in both
important natural products1 (e.g., alkaloids) and un-
natural synthetic materials,2 carbazoles have received
considerable attention in the literature, particularly in
terms of their synthetic methodology. In synthetic ma-
terials, carbazoles are an important building block for
both small-molecule and polymeric-optoelectronic ma-
terials because of their desirable electronic and charge-
transport properties, as well as their high thermal
stability. The ability to tune the carbazole’s properties
and incorporate them into more complex molecular
structures requires either the chemical functionalization
of the parent carbazole nucleus or its construction from
simple, readily available synthons.
FIGURE 1. Structure of carbazole ring system.
Owing to its highly electron-rich nature, the carbazole
skeleton (Figure 1) is a modest nucleophile that can be
readily derivatized with a wide variety of electrophiles
(tertiary alkyl, acyl, nitro, halogen, etc.).3 While com-
monly employed, such methods are limited in the posi-
tion(s) on the ring system to which electrophiles can be
introduced. The most reactive positions for electrophilic
substitution are the 3 and 6 position, “para” to the
nitrogen atom, and to a lesser extent, the 1 and 8
positions, which often require more forcing reaction
conditions. When functionalization of the 2, 4, 5, or 7 ring
positions is desired, or when mono and/or unsymmetrical
substitution patterns are needed, and/or when functional
groups not readily introduced by electrophilic substitu-
tion are desired, alternate syntheses are required. For-
tunately several methods exist for the synthesis of
(1) For some recent examples of carbazole-containing natural prod-
ucts, see: (a) Wang, Y.-S.; He, H.-P.; Shen, Y.-M.; Hong, X.; Hao, X.-J.
J. Nat. Prod. 2003, 66, 416. (b) Ito, C.; Katsuno, S.; Itoigawa, M.;
Ruangungsi, N.; Mukainaka, T.; Okuda, M.; Kitigawa, Y.; Tokuda, H.;
Nishino, H.; Furukawa, H. J. Nat. Prod. 2000, 63, 125. (c) Chakravarty,
A. K.; Sarkar, T.; Masuda, K.; Shiojima, K. Phytochemistry 1999, 50,
1263. (d) Wu, T.-S.; Huang, S.-C.; Wu, P.-L. Chem. Pharm. Bull. 1998,
46, 1459. (e) Ito, C.; Katsuno, S.; Ohta, H.; Omura, M.; Kajura, I.;
Furukawa, H. Chem. Pharm. Bull. 1997, 45, 48.
(2) For some recent references on carbazoles in materials, see: (a)
Ferreira, I. C. F. R.; Queiroz, M.-J. R. P. J. Heterocycl. Chem. 2001,
38, 749. (b) Morin, J.-F.; Leclerc, M. Macromolecules 2001, 34, 4680.
(c) Bouchard, J.; Wakim, S.; Leclerc, M. J. Org. Chem. 2004, 69, 5705.
(d) Li, H.; Zhang, Y.; Hu, Y.; Ma, D.; Wang, L.; Jing, Z.; Wang, F.
Macromol. Chem. Phys. 2004, 205, 247. (e) Kimoto, A.; Cho, J.-S.;
Miguchi, M.; Yamamoto, K. Macromolecules 2004, 37, 5531. (f) Iraqi,
A.; Wataru, I. Chem. Mater. 2004, 16, 442.
(3) (a) Neugebauer, F. A.; Fischer, H. Chem. Ber. 1972, 105, 2686.
(b) Moskalev, N. V. Khim. Geterotsikl. Soedin. 1990, 2, 187. (c) Zhu,
Z.; Moore, J. S. J. Org. Chem. 2000, 65, 116. (d) Zhu, Z.; Moore, J. S.
Macromolecules 2000, 33, 801. (e) Joule, J. A. In Advances in
Heterocyclic Chemistry; Katritsky, A. R., Ed.; Academic: Orlando, 1984;
Vol. 35, p 129.
10.1021/jo0503299 CCC: $30.25 © 2005 American Chemical Society
Published on Web 05/19/2005
5014
J. Org. Chem. 2005, 70, 5014-5019

PPh3-Mediated Reductive Cyclization of 2-Nitrobiphenyls
TABLE 1. Reaction Optimization of PPh3-Mediated
Reductive Cyclization of 2-Nitrobiphenyls: Solvent
Effects
FIGURE 2. Cadogan synthesis of carbazoles.
T
dielectric
dipole
time
(h)
%
R ) solvent (°C) constantc moment (D)c
yielda
t-Bu PhMe
t-Bu PhCl
t-Bu o-DCB
110
132
180
152
165
180
2.38
5.62
9.93
36.7
37.8
9.93
0.36
1.69
2.50
39
39
16
27
21
21
lowb
lowb
83
FIGURE 3. Reductive cyclization of 2-nitroso biphenyl de-
rivatives affords carbazoles.
H
H
H
DMF
60
carbazoles, often bearing functionality, by either ring
contraction or cyclization of suitable precursors.4,5
One of the most common methods for carbazole syn-
thesis involves the reductive cyclization of 2-nitro-
biphenyl derivatives in the presence of suitable organo-
phosphorus reagents.6 This method is commonly referred
to as the Cadogan cyclization (Figure 2) and has a
number of advantages over the electrophilic syntheses
described above, which include increased substrate scope
and functional group tolerance, and more precise regio-
control of functional group placement within the product
(determined by relative position in the biphenyl starting
material). The reaction is commonly conducted using an
excess of triethyl phosphite, as both the reductant and
reaction solvent, at reflux (156 °C). While generally
successful, this procedure exhibits considerable substrate
dependence, both in terms of the reaction time and
product distribution. We and others have found that the
desired carbazole is often contaminated by the N-ethyl
derivative, which results from alkyl transfer to the
product either directly from solvent or, more likely, from
the triethyl phosphate byproduct of the reaction.7 This
problematic side reaction is particularly prevalent when
either long reaction times or substrates bearing electron-
donating substituents are involved. Furthermore, the
undesired alkylated impurity is usually quite difficult to
remove, requiring careful, tedious chromatographic pu-
rification, which complicates the large-scale syntheses
required for industrial applications.
DMAc
o-DCB
3.81
2.50
91
91
a Yield of isolated product. b Mostly starting materials by TLC
at the indicated time. Additional PPh3 (1 equiv) added after 18 h.
c Gordon, A. J.; Ford, R. A. The Chemist’s Companion; Wiley: New
York, 1972; p 3.
To the best of our knowledge, only a single example
exists in the literature describing the use of PPh3 as a
reductant in carbazole synthesis from nitrobiphenyls.6c
In this report, Cadogan and co-workers describe a single
experiment in which 2-nitrobiphenyl is reductively cy-
clized to carbazole with molten PPh3 in a sealed tube,
with only modest yield (43%). Surprisingly, no further
examples of this or related procedures can be found, and
little description beyond the synthetic procedure was
given in the original account. While from an industrial
chemistry perspective, solventless processes are poten-
tially attractive, this particular procedure was not be-
cause of low yields and the necessity to eliminate excess
reagent and byproducts. In a related report, Cadogan and
co-workers describe the reductive cyclization of 2-nitroso-
biphenyl compounds to carbazoles using PPh3 in benzene
as solvent at low temperatures (Figure 3).8 Although this
method is unattractive because of the difficulties involved
in preparing and manipulating sensitive nitroso com-
pounds, it is significant because such compounds are
probable intermediates in the reduction of the analogous
nitro materials. In addition, and perhaps more impor-
tantly, it demonstrates that solvent does not adversely
affect the cyclization reaction.
To circumvent the problem of unwanted alkylation (i.e.,
product destruction) by the reagent or byproduct, we
decided to explore the use of alternative reducing agents
for this transformation. Triphenylphosphine is a con-
venient substitute because it is an easily handled,
inexpensive, and stable solid. Moreover, the use of PPh3
offered the possibility to remove the byproduct, tri-
phenylphosphine oxide, by a number of convenient
methods including precipitation, or simple chromatog-
raphy, thus simplifying purification.
Results and Discussion
We describe our efforts to use PPh3 to affect the
reductive cyclization of 2-nitrobiphenyls to the corre-
sponding carbazoles. 4,4′-Di-tert-butyl-2-nitrobiphenyl 1
and 2-nitrobiphenyl 2 were used as the starting materials
to help us identify suitable solvents and establish reac-
tion conditions.
The reaction setup was simple. Initially, 1 and 2.5
equivalents of PPh3 were taken up in toluene, chloro-
benzene, and o-dichlorobenzene (o-DCB), and refluxed for
39 h or until completion (Table 1). These solvents were
selected because of their similar polarity, high solvent
power, high boiling points, and availability. Interestingly,
the extent of the reaction paralleled with temperature.
After 16 h, the reaction conducted in o-DCB appeared
(4) For an overview of the common methods used to prepare
carbazoles see: (a) Kuroki, M.; Tsunashima, Y. J. Heterocycl. Chem.
1981, 18, 709. (b) Joule, J. A. In Advances in Heterocyclic Chemistry;
Katritzky, A. R., Ed.; Academic: Orlando, 1984; Vol. 35, p 83.
(5) Smitrovich, J. H.; Davies, I. W. Org. Lett. 2004, 6, 533.
(6) (a) Cadogan, J. I. G. Quart. Rev. 1962, 16, 208. (b) Cadogan, J.
I. G.; Cameron-Wood, M. Proc. Chem. Soc. 1962, 361. (c) Cadogan, J.
I. G.; Cameron-Wood, M.; Mackie, R. K.; Searle, R. J. G. J. Chem. Soc.
1965, 4831. (d) Cadogan, J. I. G. Synthesis 1969, 11. (e) Cadogan, J. I.
G. In Organophosphorus Reagents in Organic Synthesis; Cadogan, J.
I. G., Ed.; Academic: London, 1979; Chapter 6.
(7) (a) Puskas, I.; Fields, E. K. J. Org. Chem. 1968, 33, 4237. (b)
Tsunashima, Y.; Kuroki, M. J. Heterocycl. Chem. 1981, 18, 315.
(8) Bunyan, P. J.; Cadogan, J. I. G. J. Chem. Soc. 1963, 42.
J. Org. Chem, Vol. 70, No. 13, 2005 5015

Freeman et al.
TABLE 2. 2-Nitrobiphenyls Prepared by
TABLE 3. Reductive Cyclization of Nitrobiphenyls to
Carbazoles
Suzuki-Miyaura Cross-Coupling
complete, while the others were not. Removal of the
solvent, followed by simple column chromatography
afforded the desired product 3 in 83% yield, without any
unwanted N-alkylcarbazole byproducts. Unfortunately,
in the case of the toluene and chlorobenzene reactions,
the addition of another equivalent of PPh3 (after 18 h),
along with prolonged reaction times (up to 39 h), did little
to promote the conversion. Thus, the reaction performed
in o-DCB gave the highest yields in the shortest reaction
time, with the smallest excess of PPh3, presumably as a
result of the higher reaction temperature. In all cases,
conversion was cleansonly PPh3, the starting material
and product, and PPh3O were ever present. The primary
byproduct, 2 equivalents of PPh3O, could be readily
removed by either chromatography or precipitation from
hexane.
Subsequently, we probed the effects of strongly polar
solvents by conducting the reductive cyclization of 2-
nitrobiphenyl to carbazole in refluxing DMF and DMAc,
with an identical reaction in o-DCB as a control. As in
the previous reactions, temperature appeared to be the
most important parameter because DMF and DMAc are
nearly identical in terms of their dielectric constant and
polarity. The reaction in DMF (at 152 °C) proceeded to
only a moderate degree of conversion (60%), and even
after 27 h, a significant amount of 2-nitrobiphenyl
remained. Conversely, the reaction in DMAc (165 °C)
proceeded to very high conversion, with complete con-
sumption of starting material within 21 h. The control
reaction, conducted in o-DCB, gave identical results to
that done in DMAc, suggesting that solvent polarity is
not a determining factor in the outcome of the reaction.
a Reaction was run overnight, although it appeared essentially
complete at the time indicated. b TLC showed only the product,
PPh3O, and a small excess of PPh3. This product could not be
separated from the PPh3O. c Tashiro, M.; Yamato, T. Synthesis
1979, 48. d Smitrovich, J. H.; Davies, I. W. Org. Lett. 2004, 6, 533.
e Dierschke, F.; Grimsdale, A. C.; Mullen, K. Synthesis 2003, 2470.
f Allen, F. C.; Suschitzky, H. J. Chem. Soc. 1953, 3845. g Forbes,
E. J.; Wragg, R. T. Tetrahedron 1960, 8, 79. h Mayor, C.; Wentrup,
C. J. Am. Chem. Soc. 1975, 97, 7467. ijCarter, P. H.; Plant, S. G.
P.; Tomilinson, M. J. Chem. Soc. 1957, 2210. j Kyziol, J. B.;
Lyzniak, A. Tetrahedron 1980, 36, 3017. k Ghosh, S.; Datta, D. B.;
Datta, I.; Das, T. K. Tetrahedron 1989, 45, 3775. l Diaz, J. L.;
Dobarro, A.; Villacamp, B.; Velasco, D. Chem. Mater. 2001, 13,
2528. m Holzabfel, C. E.; Dwyer, C. Heterocycles 1998, 48, 1513.
n Benzies, D. W. M.; Fresneda, P. M.; Jones, R. A.; McNab, H. J.
Chem. Soc., Perkin Trans. 1 1986, 1651.
Ultimately, we settled on the use of o-DCB because of
its comparatively short reaction times and its widespread
availability and use in our laboratory. Thus, with the
general experimental conditions established, we set out
to elaborate the substrate scope and functional group
tolerance of our new method.
We first prepared a wide variety of 2-nitrobiphenyls
that possessed a range of common functionalities via
5016 J. Org. Chem., Vol. 70, No. 13, 2005

PPh3-Mediated Reductive Cyclization of 2-Nitrobiphenyls
FIGURE 4. Proposed reaction mechanism for reductive cyclization.6c,10
Suzuki-Miyaura cross-coupling between phenyl boronic
acid, and the appropriately substituted 2-halonitro-
benzene (Table 2).9 The cross-couplings were conducted
under standard conditions [Pd(PPh3)4, aqueous carbonate
base] and proceeded in excellent to quantitative yields,
in most cases, for the arylbromides and electron-deficient
aryl chlorides employed. Only in the case of the fluori-
nated nitrobiphenyl 8 was the isolated yield low, which
was mainly due to difficulties in separating the product
from unidentified impurities. Once in hand, these inter-
mediates were subjected to reductive cyclization under
our previously optimized conditionssreflux in o-DCB in
the presence of 2.5 equivalents of PPh3 until complete
consumption of the starting material. The results are
summarized in Table 3.
general, reaction times are short, with most reactions
complete within 7-8 h. Even those reactions that were
allowed to proceed overnight were essentially complete
within approximately 7 h. Moreover, we observed slight
rate acceleration for the reductive cyclization of sub-
strates bearing electron-withdrawing substituents (21-
29). We speculate that this rate enhancement likely
results from the increased efficacy of reductive deoxy-
genation (via nucleophilic attack by PPh3) of the nitro
groups, which is likely to be the rate-limiting step,
preceding the cyclization in the proposed reaction mech-
anism (Figure 4).6c,10
In addition, good to excellent isolated yields are
consistently observed for this reductive cyclization across
the range of substrates examined, nearly all of which
compare favorably to corresponding literature values. It
is important to note that the literature yields cited in
Table 3 generally pertain to substituted carbazoles
formed by cyclization or condensation/oxidation reactions
As seen in Table 3, the reaction tolerates a wide array
of functional groups, encompassing alkyls, ethers, car-
bonyls (including aldehydes and enolizable ketones),
nitriles, halogens, carboxylic esters, and amides. In
(10) (a) Smolinsky, G.; Feuer, B. I. J. Org. Chem. 1966, 31, 3882.
(b) Brooke, P. K.; Herbert, R. B.; Holliman, F. G. Tetrahedron Lett.
1973, 10, 761. (c) Sundberg, R. J. J. Org. Chem. 1965, 30, 3604.
(9) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11,
513. (b) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
J. Org. Chem, Vol. 70, No. 13, 2005 5017

Freeman et al.
on suitably derivatized precursors, rather than simple
functional group transformations (e.g., ester hydrolysis)
on substituted carbazoles.
electronic properties, as well as functional handles. Their
complete characterization is ongoing in our laboratories.
In addition, we are currently incorporating these new
building blocks into novel conjugated and nonconjugated
polymeric systems with the goal of exploiting their
localized structural diversity to achieve the maximum
diversity of properties with fewest structural perturba-
tions to the overall system. We expect to report on these
results soon.
At present, the only functional groups that appear to
be incompatible with this method are those with free,
acidic protons, such as phenols and carboxylic acids, 30
and 31, respectively. Unfortunately, we do not currently
understand the origin of this incompatibility. However,
this limitation is not severe because the desired phenols
and carboxylic acids can generally be obtained from the
corresponding alkyl aryl ethers and carboxylic esters,
respectively, following reductive cyclization.
Experimental Section
4,4′-Di-tert-butyl-2-nitrobiphenyl (1). A suspension of
4,4′-di-tert-butylbiphenyl (5.00 g, 18.77 mmol) in Ac2O (100
mL) was immersed in a room-temperature water bath. A
mixture of HOAc (5 mL) and fuming HNO3 (3 mL) was added
rapidly, dropwise via pipet. TLC indicated that the reaction
was complete within 30 min. The mixture was poured into H2O
(1 L), stirred only for a few minutes, and extracted with CH2Cl2
(100 mL, then 2 × 75 mL). The combined organic layers were
washed with 1 N NaOH (2 × 100 mL) and brine, dried over
MgSO4, and concentrated; a large volume remained (probably
Ac2O that had not hydrolyzed). The solution was then taken
up in H2O (400 mL), treated with NaOH (approximately 7-10
g), and stirred for approximately 1 h during which time a
yellow precipitate developed. The mixture was extracted with
Et2O (3 × 100 mL), and the combined layers washed with
saturated NaHCO3 (75 mL) and brine, dried over MgSO4, and
concentrated to a yellow solid. Chromatography (80:20 P950
Ligroin:CH2Cl2) gave the desired product as a pale yellow solid
In general, purification of the carbazoles is readily
achieved by column chromatography in which the only
byproduct of the reaction, triphenylphosphine oxide, is
easily separated from the relatively nonpolar product.
When carbazoles possessing highly polar functionality are
formed, separation of the PPh3O from the product can
be very difficult. Such was the case with the primary
amide 29 that formed in apparently high yield (conver-
sion estimated to be >90% by TLC) but could not be
isolated apart from the PPh3O, despite repeated chro-
matography. In this, the only case of difficulty encoun-
tered in purification, we suspect strong hydrogen bonding
between the product and PPh3O resulted in coelution,
despite good apparent thin-layer chromatographic reso-
lution.
1
(4.67 g, 80% yield): mp 113-116 °C; H NMR (CDCl3) δ 1.36
Summary and Conclusions
(S, 9H), 1.39 (s, 9H), 7.26 (ABq, 2H), 7.38 (d, J ) 8.1 Hz, 1H),
7.43 (ABq, 2H), 7.62 (dd, J ) 1.9 Hz, 8.1 Hz, 1H), 7.81 (d, J )
1.9 Hz, 1H); 13C NMR (CDCl3) δ 31.3, 31.6, 34.9, 35.1, 121.1,
126.8, 127.8, 129.5, 131.8, 133.5 134.5, 149.5, 151.2, 152.0; MS
(HR EI) m/z calcd for [M]+ 311.1885, found 311.1891. Anal.
Calcd for C20H25NO2: C, 77.14; H, 8.09; N, 4.50. Found: C,
77.24; H, 7.83, N, 4.51.
In conclusion, we have refined and expanded upon the
early single experiment reported by Cadogan and co-
workers demonstrating that PPh3 can be used to reduc-
tively cyclize 2-nitrobiphenyls to carbazoles. We have
established that the reaction can be efficiently conducted
in solvent and that the reaction temperature, rather than
the solvent polarity, is the crucial factor governing the
extent of reaction. As such, high-boiling o-DCB was found
to afford the highest yields in the shortest reaction times
for a number of substrates. Moreover, these conditions
avoid the formation of troublesome N-alkylated byprod-
ucts that often form when the trialkyl phosphite proce-
dure is used. Thus, purification is simplified to either
precipitation of the PPh3O from the product using hex-
anes, simple chromatography, or in some cases, a com-
bination of the two.
4-Benzoyl-2-nitrobiphenyl (13).: 4-Chloro-3-nitrobenzo-
phenone (2.00 g, 7.64 mmol), phenylboronic acid (1.03 g, 8.41
mmol), and K2CO3 (8 mL of 2 M aqueous solution, 15.29 mmol)
were taken up in toluene (11 mL) and sparged with N2 for 5
min. At that time, Pd(PPh3)4 (0.09 g, 0.08 mmol) was added,
and N2 sparging continued for an additional 5 min before the
reaction was fitted with a condenser and immersed in an oil
bath at 110 °C. After 17 h, the reaction was cooled, diluted
with Et2O (150 mL), and filtered. The filtrate was washed with
H2O (2 × 50 mL) and brine, dried over MgSO4, and concen-
trated in vacuo. Chromatography (gradient of 40:60 to 0:100
P950 ligroin/CH2Cl2) gave the product as a pale yellow solid
1
(2.25 g, 97% yield): mp 115-118 °C; H NMR (CDCl3) δ 7.37
Furthermore, we examined a series of substituted
2-nitrobiphenyl derivatives to elucidate the scope and
functional-group tolerance of our new experimental
conditions. The breadth of substrates amenable to reduc-
tive cyclization using PPh3 at elevated temperatures is
substantial and includes reactants possessing halogens,
alkyl groups, ethers, carbonyls, and several carboxylic
acid derivatives. The desired carbazole products are
formed cleanly and in good yields. Reaction times are
generally short, and the reaction seems to proceed more
rapidly with electron-deficient substrates. Only in the
case of the most polar products, and where strong
hydrogen bonding is possible, is separation of PPh3O
difficult. Although the reason is unclear, the only sub-
strates not tolerated by this reaction are those bearing
acidic hydrogens, such as phenols and carboxylic acids.
This chemistry has allowed us to prepare a series of
highly pure carbazoles with a spectrum of optical and
(dd, J ) 2.2 Hz, 6.0 Hz, 2H), 7.43-7.50 (m, 3H), 7.50-7.70
(m, 4H), 7.82-7.89 (m, 2H), 8.06 (dd, J ) 1.9 Hz, 8.1 Hz, 1H),
8.26 (d, J ) 1.8 Hz, 1H); 13C NMR (CDCl3) δ 125.7, 128.0,
128.9, 129.1, 130.2, 132.4, 133.3, 133.5, 136.6, 136.6, 137.7,
140.0, 149.4, 194.1; MS (HR EI) m/z calcd for [M]+ 303.0895,
found 303.0898. Anal. Calcd for C19H13NO3: C, 75.54; H, 4.32;
N, 4.62. Found: C, 75.14; H, 4.21; N, 4.58.
N-Butyl-2-nitrobiphenyl-4-carboxamide (15). N-butyl-
4-chloro-3-nitrobiphenyl carboxamide (1.50 g, 5.84 mmol),
phenylboronic acid (0.78 g, 6.43 mmol), and K2CO3 (6 mL of 2
M aqueous solution, 11.69 mmol) were taken up in toluene
(7.6 mL) and sparged with N2 for 5 min. At that time,
Pd(PPh3)4 (0.07 g, 0.06 mmol) was added, and N2 sparging
continued for an additional 5 min before the reaction was fitted
with a condenser and immersed in an oil bath at 110 °C. After
20 h the reaction was cooled, diluted with Et2O (150 mL), and
filtered. The filtrate was washed with H2O (2 × 50 mL) and
brine, dried over MgSO4, and concentrated in vacuo. Chroma-
tography (gradient of 0:100 to 5:95 Et2O:CH2Cl2) gave the
product as a yellow powder (1.71 g, 98% yield): mp 91-94 °C;
5018 J. Org. Chem., Vol. 70, No. 13, 2005

PPh3-Mediated Reductive Cyclization of 2-Nitrobiphenyls
1H NMR (CDCl3) δ 0.99 (t, J ) 7.1 Hz, 3H), 1.44 (sextet, J )
7.9 Hz, 2H), 1.65 (quintet, J ) 2.6 Hz, 2H), 3.51 (q, J ) 5.9
Hz, 2H), 6.21 (bs, 1H), 7.30 (dd, J ) 3.5,Hz, 7.3 Hz, 2H), 7.41-
7.47 (m, 3H), 7.54 (d, J ) 8.1 Hz, 1H), 8.03 (dd, J ) 1.8 Hz,
8.1 Hz, 1H), 8.21 (d, J ) 1.6 Hz, 1H); 13C NMR (CDCl3) δ 14.0,
20.4, 31.6, 40.4, 122.8, 128.0, 128.9, 129.9, 130.9, 132.6, 135.1,
136.7, 139.1, 149.3, 165.1; MS (HR EI) m/z calcd for [M]+
298.1317, found 298.1314. Anal. Calcd for C17H18N2O3: C,
68.44; H, 6.08; N, 9.39. Found: C, 68.89; H, 5.99; N, 9.44.
4′-tert-Butyl-2-nitrobiphenyl (17). A mixture of 2-bromo-
nitrobenzene (2.50 g, 12.38 mmol), 4-tert-butylphenylboronic
acid (2.42 g, 13.61 mmol). and K2CO3 (13 mL of 2 M aqueous
solution) was taken up in toluene (20 mL) and sparged with
bubbling N2 for approximately 5 min before Pd(PPh3)4 (0.21
g, 0.19 mmol) was added. After sparging for an additional 10
min, the orange reaction was refluxed with vigorous stirring
for 17 h. The reaction was filtered through filter paper and
washed with Et2O (250 mL). The organic phase was washed
with H2O (3 × 50 mL) and brine, dried over MgSO4, and
concentrated to a dark-colored oil. Chromatography (75:25
P950 ligroin/CH2Cl2) gave the product as a viscous yellow oil
(3.05 g, 97% yield): 1H NMR (CDCl3) δ 1.37 (s, 9H), 7.27 (ABq,
2H), 7.43-7.50 (m, 4H), 7.58-7.63 (m, 1H), 7.81-7.85 (m, 1H);.
13C NMR (CDCl3) δ 31.6, 34.9, 124.2, 125.9, 127.8, 128.1, 132.2,
132.4, 134.5, 136.4, 149.7, 151.5; MS (HR EI) m/z calcd for [M]+
255.1259, found 255.1255. Anal. Calcd for C16H17NO2: C,
75.27; H, 6.71; N, 5.49. Found: C, 75.26; H, 6.82; N, 5.63.
2,7-Di-tert-butylcarbazole (3). A solution of 4,4′-di-tert-
butyl-2-nitrobiphenyl (1.00 g, 3.21 mmol) and PPh3 (2.11 g,
8.04 mmol) in o-DCB (6.5 mL) was heated to reflux with
vigorous stirring. After 16 h, the solvent was stripped under
high vacuum and the resulting dark orange semisolid slurried
in P950 ligroin (15 mL) to precipitate the PPh3O, which was
removed by filtration. Chromatography of the filtrate (100:0,
then 75:25 P950 ligroin/CH2Cl2) gave the product as a white
solid (0.75 g, 83% yield): 1H NMR (DMSO-d6) δ 1.37 (s, 18H),
7.20 (dd, J ) 8.3 Hz, 1.6 Hz, 2H), 7.40 (d, J ) 1.1 Hz, 2H),
7.92 (d, J ) 8.3 Hz, 2H), 10.93 (s, 1H). Spectroscopic data and
analytical characterization are consistent with the literature.11
Carbazole (4). A solution of 2-nitrobiphenyl (1.19 g, 5.98
mmol) and PPh3 (3.92 g, 14.85 mmol) in o-DCB (12 mL) was
heated to reflux with vigorous stirring for 21 h, during which
time the color changed from yellow to brown. At that time,
the reaction was cooled to room temperature and concentrated
under high vacuum. Chromatography of the yellow residue (75:
25 P950/CH2Cl2) gave the product as a flaky, lustrous solid
(0.91 g, 91% yield): 1H NMR (CDCl3) δ 7.19-7.27 (m, 2H),
7.39-7.46 (m, 4H), 8.08 (d, J ) 7.8 Hz, 2H). Spectroscopic data
and analytical characterization are consistent with a com-
mercially available sample.
Acknowledgment. We thank Dr. Thomas Jackson
for the high-resolution mass spectrometry (HRMS) data.
Supporting Information Available: Experimental pro-
cedures and spectroscopic data for compounds 5-12, 14, 16,
and 18-29. Complete characterization data is provided for all
new compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
JO0503299
(11) (a) Tashiro, M.; Yamato, T. Synthesis 1979, 48. (b) Tashiro, M.;
Fukuda, Y.; Yamato, T. Heterocycles 1981, 16, 771. (c) Yamato, T.;
Hideshima, C.; Suehiro, K.; Tashiro, M.; Prakash, G. K. S.; Olah, G.
A. J. Org. Chem. 1991, 56, 6248.
J. Org. Chem, Vol. 70, No. 13, 2005 5019