Page 1 of 4
ChemComm
DOI: 10.1039/C4CC08579E
RSCPublishing
ChemCommun
COMMUNICATION
Cu(NO ) ·3H OꢀMediated Cyanation of Aryl Iodides
3
2
2
and Bromides using DMF as a Single Surrogate of
Cyanide
Cite this: DOI: 10.1039/x0xx00000x
Received 00th January 2012,
Accepted 00th January 2012
Lianpeng Zhang, Ping Lu* and Yanguang Wang*
DOI: 10.1039/x0xx00000x
www.rsc.org/
Aryl nitriles were prepared through Cu(NO ) ·3H Oꢀ dimethylforamide (DMF) as a single surrogate of “CN” source
3
2
2
(Scheme 1).
mediated cyanation of aryl iodides and bromides using DMF
as a single surrogate of cyanide. Moreover, this protocol
could be scalable and practice with operational benign.
Aryl nitriles are versatile intermediates in organic synthesis
because they could be easily transferred into various valuable
functional groups, such as carboxylic acids, amidines, and amines, or
1
2
converted into heterocycles, such as pyrazoles, triazoles, and
3
tetrazoles. Due to these practical transformations, development of
new methodology leading to a cheap, safe, and feasible preparation
method of aryl nitriles is still demanding, especially important in
industry.
There are two classes of starting materials for the preparation of
4
aryl nitriles. One is aryl halides, and the other is arenes in which the
cyanation of arene happens through transition metal catalyzed CꢀH
activation with/without directing group. Although the direct CꢀH
5
Scheme 1 Organic Cyanide Surrogates Applied in CuꢀCatalyzed /
Mediated Cyanations.
functionalization is becoming more and more attractive and
challengeable to organic chemists because of the exhilarating and
6
fascinating mechanisms, aryl halides are still favourable because of
Initially, we tested the reaction of 4ꢀiodoanisole (1a) and DMF
their reaction orientation and broad availability.
o
in the presence of CuI, acetic acid, and TBHP under air at 130 C for
Among the transition metal catalyzed cyanations of aryl
halides, researches have been focusing on the discovery of metal
catalysts and various operational benign cyanide sources. Although
palladium catalyzed cyanations possessed high efficiencies, they still
have drawbacks, such as expensive palladium catalysts as well as
4
4
8 h (Table 1, entry 1). 4ꢀCyanoanisole (2a) was indicated by GC in
5% conversion yield. Screening the copper sources,
Cu(NO ) ·3H O was determined to be the optimal (Table 1, entries
3
2
2
1
ꢀ12). Mediated by Cu(NO ) ·3H O, the conversion yield of 2a was
3 2 2
7
determined to be 73%, while the isolated yield of 2a was obtained as
9% (Table 2, entry 8). Increasing or decreasing the amount of
Cu(NO ) ·3H O, the yield of 2a was dropped (Table 2, entries 13
their special ligands required. Beside of this, palladium catalyst
6
would be easily poisoned by the excess amount of cyanide anion due
8
3
2
2
to the large affinity of cyanide anion to palladium. By comparison,
and 14). Subsequently, the optimal amount of HOAc and TBHP was
determined to be 4 and 2 equivalents (Table 1, entries 15ꢀ18). The
yield was largely depended upon the reaction temperature and
reaction atmosphere. The best yield was achieved by increasing the
copper salt is much cheaper and operational benign. In most cases,
copper catalyzed or mediated cyanations could be conducted under
5
b
air without specific ligands. Metal cyanides are traditionally used
CN” sources, but with high toxicity. Organic cyanide surrogates
“
o
reaction temperature to 140 C (Table 1, entries 19ꢀ20). Under
slowly release cyanide anion during the reaction process
9
nitrogen, the yield dropped to 19%, while the yield kept the same
surmounting the safety problem and are operational benign. These
(
89%) under oxygen (Table 1, entries 21ꢀ22). Without TBHP
oxidant, the reaction worked, but with relatively lower yields (air:
4%; O : 78%, Table 1, entries 23 and 24). It was noticeable that the
organic sources could be classified into two categories. One is
“CN”ꢀcontaining, the other is nonꢀ“CN”ꢀcontaining in which C≡N
3
2
triple bond forms as the reaction goes. Scheme 1 listed the organic
cyanide surrogates which have been applied in copperꢀcatalyzed or
copperꢀmediated cyanations of aryl halides.
conversion yield of 2a was 55% without HOAc (Table 1, entry 25).
These two reactions indicated that the carbon source of “CN” did not
come from HOAc or THBP. Thus, the optimal reaction conditions
were established: running the mixture of ArX, Cu(NO ) ·3H O,
Herein, we would like to report a practical method for the
preparation of aryl nitriles from aryl bromides / iodides in the
presence of stoichimetric amount of Cu(NO ) ·3H O by using N,N’ꢀ
3
2
2
o
HOAc, and TBHP (1:1.2:4:2) in DMF under air at 140 C for 48 h
Table 1, entry 20).
3
2
2
(
This journal is © The Royal Society of Chemistry 2012
J. Name., 2014, 00, 1-4 | 1