172
Chemistry Letters Vol.36, No.1 (2007)
Carbazole Synthesis by Platinum-catalyzed C–H Functionalizing Reaction
Using Water as Reoxidizing Reagent
Mitsuru Yamamoto and Seijiro Matsubaraꢀ
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Kyoutodaigaku-katsura, Nishikyo-ku, Kyoto 615-8510
(Received November 16, 2006; CL-061346; E-mail: matsubar@orgrxn.mbox.media.kyoto-u.ac.jp)
Treatment of 1-aminobiphenyl and diphenylamine with
degassed by bubbling N2 gas for 30 min in advance. The internal
catalytic amount of Pt/C in hydrothermal water (250 ꢁC,
4 MPa) affords 9H-carbazole in good yield. In this catalytic
cycle, water works as reoxidizing reagent for platinum catalyst.
pressure reached 4 MPa. The combination was heated at the
same temperature for 12–48 h. After cooling, the mixture was
extracted with ethyl acetate. Platinum was shown to be effective
for the cyclization. Carbazole 2 was obtained in 76% yield after
12 h heating in the presence of 5 mol % Pt/C (10 wt % on active
carbon).
Transition metal-catalyzed cross-coupling reactions are
among the most popular processes in modern organic synthesis.1
As the research has been focused not only on C–C bond-forming
reactions but also on C–N bond-forming reactions,2 the prepara-
tion of carbazoles by the cross-coupling reaction has been devel-
oped using the ring-closure with C–N or C–C bond-forming re-
actions.3 Recently, these synthetic routes have gained additional
diversity because of the development of C–H bond functionali-
zation.4 By this method, carbazole derivatives can be prepared
without using an organic halide as substrate. For example,
C–H functionalization in N-acyl-1-aminobiphenyl by palladium
catalyst followed by C–N bond coupling reaction afforded N-
acylcarbazole.5 This Pd-catalyzed reaction was driven by copper
salt and oxygen gas as reoxidant of the catalyst. In the same
manner, the Pd-catalyzed C–H bond functionalization in N-
phenylaniline followed by C–C bond-forming reaction also gave
the carbazole under O2 atmosphere as reoxidizing reagent of the
catalyst.6 These oxidizing reagents are indispensable in order
to maintain a catalytic cycle, because the key species for C–H
functionalization in both transformations was PdII species,
which will be converted into Pd0 species at the terminal reduc-
tive elimination. Although oxygen gas is a relatively mild
reagent, it may still cause a limitation of the substrate and the
process. We tried to use hydrothermal water as an oxidizing re-
agent. Recently, we had reported that treatment of hydrocarbons
with hot deuterium oxide (250 ꢁC/4 MPa) in the presence of Pd
or Pt catalyst resulted in a complete H/D exchange reaction.7
This process includes C–H functionalization with PdII or PtII
which is formed by an oxidation with deuterium oxide as shown
in eqs 1 and 2.8 These results implied that the carbazole synthesis
based on C–H fuctionalization with a transition-metal catalyst
may be driven by water as the reoxidizing reagent.
cat
(3)
H O, 250 °C
12 h
2
NH
2
NH
2
1
Catalyst (/mol %) Yield of 2/% recovery/%
Pd/C (5)
Pd(OAc) (5)
Pt/C (5)
Pt/C (3)
7
5
76
90
93
< 3
77
2
16
The yields of carbazole derivatives 4 from 2-aminobiphenyl
derivatives 3 by treatment with hot water and platinum catalyst
are summarized in Scheme 1. The low yield of carbazole 4c from
2-amino-40-methylbiphenyl (3c) compared to the moderate yield
of 2 from 1 was notable.
The C–H functionalization on aromatic ring by PtII is con-
sidered to proceed via electrophilic substitution like a Friedel–
Crafts reaction.9 In order for carbazole 4c to be formed, C–H
functionalization should occur at 20 or 60-position in biphenyl-
amine derivative 3c. As shown in eq 4, treatment of 3c in D2O
with platinum catalyst for 2 h at 250 ꢁC afforded deuterated 3c
with 11% yield of 4c. Distribution of D-atom in recovered 3c im-
plies the efficiency of C–H functionalization.10 Amino-group has
strong orientation and acceleration of electrophilic substitution
at o- and p-position on benzene ring, and methyl-group also
has moderate those on benzene ring. In addition to these elec-
tronic effects, a steric hindrance may rationalize the low distribu-
tion of D-atom at 20 and 60-position in 3c-dn in eq 4. As the result,
4c could not be formed in good yield because of the low efficien-
cy of C–H functionalization at 20 and 60-position in 3c.
H
NH
Ar
2
Pt/C (5 mol %)
N
H C
3
H O, 250 °C
48 h
H C
2
3
3
4
+ [OD]
Pt
+
D O
D–Pt–OD
Pt–D
[D–Pt ]
+ H
(1)
(2)
2
H
H
N
H
N
N
H C
H C
3
3
D
+ Pt
CH
CH
3
3
+
Pt–D
H C
H C
3
3
4a (66%)
4b (72%)
4c (38%)
H
We examined two types of carbazole syntheses: One was
H
N
N
metal-catalyzed C–N bond-forming cross-coupling reaction in
a 2-biphenylamine derivative and the other was metal-catalyzed
C–C bond-forming cross-coupling reaction in a diarylamine
derivative. As shown in eq 3, 2-aminobiphenyl (1, 2.0 mmol)
was treated with metal catalyst (3–5 mol %) and water (15 g)
in a 30-mL TeflonÓ-lined autoclave at 250 ꢁC.8 The water was
H C
3
4d (44%)
4e (48%)
Scheme 1. Preparation of carbazole derivatives 4 from 2-bi-
phenylamine derivatives 3 (Bold line is the newly formed bond).
Copyright Ó 2007 The Chemical Society of Japan