DOI: 10.1002/chem.201303680
Communication
&
Synthetic Methods
A Versatile and Highly Efficient Method for 1-Chlorination of
Terminal and Trialkylsilyl-Protected Alkynes
Nurbey Gulia, Bartłomiej Pigulski, Marta Charewicz, and Sławomir Szafert*[a]
yields are observed. Additionally, this reaction was only applied
Abstract: A highly efficient one-pot procedure for the
to a few compounds.
preparation of 1-chloroalkynes and 1-chlorobutadiynes
Herein, we report a new, convenient, and high-yielding pro-
from terminal and trialkylsilyl-protected precursors is re-
cedure that leads to 1-chloroalkynes and 1-chlorobutadiynes
ported. This convenient reaction, proceeding under mild
from trialkylsilyl-protected compounds, as well as from termi-
conditions, utilizes N-chlorosuccinimide as the chlorinating
nal alkynes. To avoid multiple chlorinations occurring, NCS was
agent and tolerates a range of functional groups.
selected as the chlorinating agent because of its lower activity,
compared with that of TCCA.[12] In search of an effective reac-
tion system, 4-(trimethylsilylethynyl)benzonitrile has been se-
1-Chloroalkynes are attracting increasing interest in the scien-
tific community owing to their use in organic and organome-
tallic synthesis. Such species have been applied in numerous
areas, such as carbonÀcarbon bond-forming reactions,[1]
syntheses of various haloalkene derivatives,[2] and cyclization
reactions.[3]
lected as a model compound owing to the ease of its prepara-
tion and the low volatility of the corresponding chloride.
The resulting yields for the different reaction systems are
shown in Table 1. Conditions analogous to those for bromina-
tion and iodination[13] (Table 1, entry 1) did not lead to the cor-
Classically, 1-chloroalkynes are obtained from terminal al-
kynes by using a strong base and an appropriate chlorinating
agent.[4] A typical reaction pathway proceeds through a depro-
tonated alkyne and prevents the use of some functional
groups, for example the hydroxyl group. Other important
routes towards the synthesis of 1-chloroalkynes include the
chlorination of terminal alkynes by using hypochlorites,[5] the
Table 1. Screening of reaction systems.
Entry Conditions [(equiv)]
Yield [%][a]
2a
3a
use
a AgOAc/NCS (Ac=acetyl, NCS=N-chlorosuccinimide)
1
2
3
4
5
6
NCS (1.5), AgF (1.0), acetone, 22 h[b]
NCS (2.0), AgOTf (0.3), acetone, 24 h
NCS (1.2), KF (0.3), AgNO3 (0.3), acetone, 6 h
NCS (1.2), KOH (18), AgNO3 (0.3), DMF, 45 min[c]
NCS (1.2), K2CO3 (3.0), AgNO3 (0.3), acetone, 30 h[d] 12
0
0
6
0
0
84
46
0
system[6] or a CCl4/K2CO3/TBAF (TBAF=tetrabutylammonium
fluoride) system,[7] and the use of phase-transfer catalysis.[8]
The use of terminal alkynes, although common, can some-
times be problematic because these compounds can be unsta-
ble, especially long homologs. Trialkylsilyl end-capped alkynes
and polyynes are usually much more stable[9] and are widely
used. Therefore, the direct chlorination of silyl-protected al-
kynes could be a very valuable route towards 1-chloroalkynes.
Although the preparation of 1-bromo- and 1-iodoalkynes
from trialkylsilyl-protected acetylenes is well known,[10] the
analogous synthesis of 1-chloroalkynes presents a challenge.
To the best of our knowledge, there is only one report on such
a transformation, which describes the use of TCCA (trichloro-
isocyanuric acid) as the chlorinating agent.[11] Nevertheless,
a long reaction time or microwave heating is required and for
some compounds multiple chlorination products and low
44
9
NCS (2.4), TBAF (1.0), AgNO3 (0.3), DMF, 20 h
65
[a] Relative quantities of products were estimated from the NMR spectra
and yields were calculated in reference to the starting material. [b] Only
starting material was recovered. [c] Decomposition of starting material
was observed. [d] Carried out under reflux.
responding 1-chloroalkyne. The use of AgOTf (OTf=trifluoro-
methanesulfonate) led to the corresponding terminal alkyne
(Table 1, entry 2). AgNO3/KF (Table 1, entry 3) enabled the reac-
tion, but provided the product in low yield, probably because
of the limited solubility of KF. A similarly poor result was ob-
tained for the K2CO3/AgNO3 system (Table 1, entry 5), whereas
the KOH/AgNO3 mixture (Table 1, entry 4) was not effective at
all. Finally, the most promising results were obtained by using
an AgNO3/TBAF system (Table 1, entry 6), which was then se-
lected for further optimization.
[a] Dr. N. Gulia,+ B. Pigulski,+ M. Charewicz, Dr. S. Szafert
Department of Chemistry, University of Wrocław
14F. Joliot-Curie, 50-383 Wrocław (Poland)
[+] These authors contributed equally to this work.
Following this result, the influence of the solvent and the
quantity of reactants (Table 2) were investigated. The results
showed that a TBAF/AgNO3 ratio of 2:1 (Table 2, entries 1–6)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201303680.
Chem. Eur. J. 2014, 20, 2746 – 2749
2746
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