Angewandte
Communications
Chemie
Azo Compounds
À
Dehydrogenation of the NH NH Bond Triggered by Potassium tert-
Butoxide in Liquid Ammonia
Lei Wang,* Akiko Ishida, Yasuyuki Hashidoko, and Makoto Hashimoto*
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Abstract: A novel strategy for the dehydrogenation of the NH
NH bond is disclosed using potassium tert-butoxide (tBuOK)
in liquid ammonia (NH3) under air at room temperature. Its
synthetic value is well demonstrated by the highly efficient
synthesis of aromatic azo compounds (up to 100% yield,
3 min), heterocyclic azo compounds, and dehydrazination of
phenylhydrazine. The broad application of this strategy and its
benefit to chemical biology is proved by a novel, convenient,
one-pot synthesis of aliphatic diazirines, which are important
photoreactive agents for photoaffinity labeling.
liminary treatment of ketones by NH3 to form imines,
subsequent reaction with NH2OSO3H to afford diaziridines
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(intermediates containing the NH NH bond), and dehydro-
=
genation to give diazirines (products containing the N N
bond) by either I2/Et3N or freshly prepared Ag2O (Sche-
me 1a).[9] Despite the prevalence of these methods,[10] they
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D
ehydrogenation of the NH NH bond is a crucial trans-
formation in chemistry, as the generated products which
=
contain a N N double bond are of great interest in various
fields. For instance, aromatic azo compounds, an important
=
type of component bearing N N bonds, are ubiquitous motifs
in therapeutic agents, food additives, indicators, dyes, pig-
ments, chemosensors, polymers, photochemical switches, and
radical-reaction initiators.[1] The recent past has witnessed
numerous methods for the synthesis of aromatic azo com-
pounds such as oxidative coupling of anilines,[2] reduction of
nitroaromatics,[3] coupling of diazo salts with aromatic com-
pounds,[4] and the Mills reaction.[5] The direct dehydrogen-
ation of hydrazo derivatives would be additional indispen-
sable methods for preparing aromatic azo compounds. How-
ever, there are few reports on the dehydrogenation of hydrazo
derivatives to afford azo compounds in the presence of either
a catalyst or substoichiometric reagent. Utilizing either O2 or
H2O2 as an oxidant, NH4VO3, a CoII complex, CuCl2, TiCl3/
HBr, Pd(OAc)2, a carbon nanotube-rhodium nanohybrid
system, and reduced graphene oxide are able to catalyze this
transformation.[6] Additionally, with KClO3/H2SO4 as an
oxidant, a catalytic amount of FeSO4 is also feasible for this
reaction.[7] Nevertheless, many methods suffer from long
reaction times, special catalysts, and relatively tedious post-
treatment. The discovery of a novel, concise, rapid, and
effective method is keenly pursued.
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Scheme 1. Dehydrogenation of the NH NH bond triggered by tBuOK
and its synthetic applications.
are fraught with many issues such as tedious experimental
procedures, the requirement for protection under either a N2
or Ar atmosphere, inevitable filtration of the solid by-
product, requirement for complete removal of NH3 before
oxidation by I2, and relatively low reaction yields. In this
respect, a convenient and effective alternative method for the
synthesis of aliphatic diazirines is highly desirable.
Herein, we describe the development of a novel and
efficient strategy for the dehydrogenation of a NH NH bond
to construct a N N double bond (Scheme 1). This method
uses the commercially available, cheap, and easily handled
tBuOK to trigger the dehydrogenation process. Numerous
aromatic azo compounds are readily synthesized in excellent
yields within 3 minutes. Importantly, with this strategy,
a novel, convenient, and effective one-pot synthesis of
aliphatic diazirines is achieved, and can significantly improve
the development of aliphatic diazirines for photoaffinity
labeling[11] (Scheme 1b).
Initially, hydroazobenzene 1a was used as a model sub-
strate for the optimization of the reaction conditions. By
employing 20 mol% NaH in THF at room temperature, we
observed the dehydrogenated product 2a in 13% yield
(Table 1, entry 1). Solvent screening indicated that DMSO
was effective and the reaction at 608C could readily produce
2a in 92% yield within 2 hours (entries 2–5). Remarkably,
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Aliphatic diazirines, three-membered ring structures
=
which contain an N N bond, are widely utilized as photo-
affinity labeling agents in chemical biology.[8] Conventionally
synthetic methods for aliphatic diazirines involve the pre-
[*] Dr. L. Wang, A. Ishida, Prof. Dr. Y. Hashidoko, Dr. M. Hashimoto
Division of Applied Bioscience, Graduate School of Agriculture
Hokkaido University
Kita 9, Nishi 9, Kita-ku, Sapporo 060-8589 (Japan)
E-mail: lei870610@gmail.com
Supporting information for this article can be found under:
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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