1672
Published on the web December 8, 2012
Transition-metal-free Benzylic C-H Bond Intermolecular Amination
Utilizing Chloramine-T and I2
Youhei Takeda,1,2 Junpei Hayakawa,1 Kazuki Yano,1 and Satoshi Minakata*1
1Department of Applied Chemistry, Graduate School of Engineering, Osaka University,
2-1 Yamadaoka, Suita, Osaka 565-0871
2Frontier Research Base for Global Young Researchers, Graduate School of Engineering,
Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871
(Received September 13, 2012; CL-120942; E-mail: minakata@chem.eng.osaka-u.ac.jp)
a
Table 1. C-H amination of indane using chloramine-T and I2
An intermolecular benzylic C-H bond amination utilizing
NHTs
the combination of chloramine-T and I2 without the aid of
transition-metal catalysts has been developed. The reaction was
found applicable to a variety of benzene-substituted alkanes, as
well as to an adamantane derivative to give N-alkylated p-
tosylamides in good yields.
O
I2 (1 equiv)
rt, 20 h
Cl
Ts
+
+
N
Na
2a
1a
• 3H2O
(1 equiv)
Combined
yield/%b
Ratio
(1a:2a)b
Entry
Solvent
Direct functionalization of C-H bonds has been a hot
topic in the field of modern synthetic organic chemistry.1
Specifically, direct amination of C-H bonds allows for
providing amine compounds, which are ubiquitous in bio-
logically active agents such as natural products and pharma-
ceuticals. Therefore, the development of direct C-H amination
reactions (the term “amination” used here includes amidation
1
2
3
4
5
6
7
Benzene
Cl2CHCHCl2
CH2Cl2
CHCl3
CH3CN
AcOEt
57
53
49
81
37
41
38
81:19
85:15
84:16
91:9
41:59
33:64
29:71
and imidation as
a broad definition) is of significant
Acetone
importance. In this context, transition-metal-catalyzed insertion
reactions of nitrenoid species into C-H bonds have been
intensively developed2 since the advent of seminal works
by Breslow and Gellman in the early of 1980s.3 On the
other hand, transition-metal-free counterparts have been
less explored to date, although such reactions would be
beneficial with respect to economic and environmental points
of view,4-10 which have employed stoichiometric organic
aReaction conditions: indane (0.5 mmol), chloramine-T trihy-
drate (0.5 mmol), and iodine (0.5 mmol) were stirred in the
solvent indicated under N2 atmosphere at room temperature for
20 h. The reaction mixture was quenched with Na2S2O3(aq)
(1 M). The values determined by H NMR integration of the
crude products.
b
1
oxidants such as PhI(OAc)2,5 PhI(OAc)2 and I2,6 DIH,7
serve as a single-electron-oxidant as well as an N1 source,
realizing less-costly C-H amination reaction.
¹ 8
TEMPO+BF4
,
or bromanes.9 Recently, catalytic variants
have also been emerging as alternative approaches to direct
C-H amination.10 Thus, the development of direct C-H bond
amination reactions under transition-metal-free conditions is an
attractive task of synthetic research.
Herein we present a transition-metal-free intermolecular
benzylic C-H amination reaction that utilizes the combination of
easy-handling and inexpensive oxidants, chloramine-T and I2.
The reaction can be operated under extremely mild reaction
conditions of room temperature to give N-alkylated p-tosyl-
amides in good to high yields.
In our continuous efforts to explore unique reactions
utilizing haloamine salts,11 we have recently developed an
iodoamidation reaction of alkenes with stoichiometric amounts
of chloramine-T and I2 in aqueous media.12 The concomitant use
of chloramine-T and iodine generates N-iodo-N-chlorosulfon-
amide TsNCl(I), which serves as a good iodonium donor given
that C=C double bonds are present in reactants. Concurrently,
we have revealed that TsNCl(I) also serves as a radical source
when a strong electron-acceptor such as fullerene derivatives
exists.13 In conjunction with the fact that hydrocarbons having
benzylic C-H bonds are amenable to single-electron-oxidation
to generate benzyl radicals, we envisaged that TsNCl(I) would
To validate this hypothesis, we treated indane with an
equimolar mixture of chloramine-T and I2 at room temperature
in several kinds of organic solvents (Table 1).14 Gratifyingly, the
benzylic C-H amination in benzene successfully proceeded to
give aminated indane 1a as a major product, together with
indanone (2a) as a minor in 57% combined yield with the ratio
of 81:19 (Entry 1). Among less-polar solvents tested (Entries
2-4), chloroform was the best in terms of chemical yield and the
ratio of 1a and 2a (Entry 4). In contrast, when more-polar
solvents such as acetonitrile, ethyl acetate, and acetone were
used, the propensity of the product ratios was inverted, affording
2a as a major product (Entries 5-7). The addition of I2 was
indispensable for the progression of the amination reaction,
since no products were obtained without iodine. In respect to the
amounts of iodine, an equimolar amount was required to obtain
the products in satisfying yields, while the use of catalytic
amounts of I2 (20 mol %) gave 1a and 2a in only 34% and 4%
yields, respectively.
It would be reasonable to consider that the oxygen atom of
2a originates from the water of chloramine-T trihydrate. In fact,
the exclusion of moisture from the reaction system by using
anhydrous chloramine-T, which was easily prepared by drying
Chem. Lett. 2012, 41, 1672-1674
© 2012 The Chemical Society of Japan
Takeda, Youhei
