Cleavage of the Carbon–Carbon Triple Bonds of Arylacetylenes for the Synthesis of Arylnitriles without a Metal Catalyst

Article abstract of DOI:10.1002/ejoc.201600438

Cleavage of the carbon–carbon triple bonds of alkynes was achieved, which led to the synthesis of arylnitriles under transition-metal-free conditions. A vast range of terminal alkyne substrates underwent this reaction to provide the corresponding nitriles in moderate to good yields with good functional group tolerance.

Full text of DOI:10.1002/ejoc.201600438

DOI: 10.1002/ejoc.201600438
Communication
Cleavage Reactions
Cleavage of the Carbon–Carbon Triple Bonds of Arylacetylenes
for the Synthesis of Arylnitriles without a Metal Catalyst
Yuanguang Lin[a] and Qiuling Song*[a]
Abstract: Cleavage of the carbon–carbon triple bonds of alk- alkyne substrates underwent this reaction to provide the corre-
ynes was achieved, which led to the synthesis of arylnitriles sponding nitriles in moderate to good yields with good func-
under transition-metal-free conditions. A vast range of terminal tional group tolerance.
Introduction
Herein, we present our discovery on the ability to achieve the
metal-free nitrogenation of terminal alkynes to produce aryl-
nitriles by using BnNHCH3 as the catalyst and molecular oxygen
as the terminal oxidant [Scheme 1, Equation (4)].
Carbon–carbon bond activation is a long-standing theme in or-
ganic chemistry and is considered as a holy grail in organic
synthesis. During the past decade, significant progress has been
made on the cleavage of carbon–carbon single bonds and the
activation of carbon–carbon double bonds.[1] However, the
cleavage of the carbon–carbon triple bonds of alkynes is much
less reported and is still regarded as one of the most challeng-
ing subjects in organic chemistry.[2] Most studies on the activa-
tion of the triple bonds of alkynes involve the utilization of
stoichiometric organometallic reagents and oxidants,[3] such as
oxidative cleavage.[4] In 2003, Liu et al. reported that ethynyl
alcohols can be split into alkenes and CO through ruthenium-
catalyzed triple bond cleavage.[5] Guo discovered that triple
bonds can be cleaved by gold-catalyzed cascade cyclization.[6]
Wang and Jiang reported a palladium-catalyzed alkyne cleav-
age reaction with molecular oxygen promoted by a Lewis
acid.[7] However, these methods suffer from multiple limitations,
including environmental unfriendliness and the use of costly
catalysts, which makes their application less desirable.
In 2013, important progress was made by the Jiao group:
they developed a silver-catalyzed carbon–carbon triple bond
cleavage reaction to afford nitriles from alkynes by using TMSN3
as the nitrogen source [Scheme 1, Equation (1)].[8] Subse-
Scheme 1. Transformation of alkynes into arylnitriles; DCE = 1,2-dichloro-
ethane.
quently, Yanada discovered
a metal-free nitrile synthesis
from alkynes by using TMSN3 as the nitrogenating agent and
stoichiometric N-iodosuccinimide (NIS) as the oxidant
[Scheme 1, Equation (2)].[9] Very recently, during the prepara-
tion of this manuscript, Maiti and co-workers reported the
metal-free nitrogenation of terminal alkynes to generate aryl-
nitriles by using tert-butyl nitrite as the nitrogen source and an
N-oxide as the oxidant [Scheme 1, Equation (3)].[10] Compared
to N-oxides, molecular oxygen is an ideal oxidant because of its
abundance, ready availability, and environmental friendliness.
Results and Discussion
We commenced our investigation with 1-(tert-butyl)-4-ethynyl-
benzene (1a) as the substrate; interestingly, upon treating 1a
with tert-butyl nitrite in acetonitrile, arylnitrile 2a was obtained
in 21 % yield (Table 1, entry 1). Encouraged by this result, we
next investigated several typical solvents such as toluene, diox-
ane, DMF, and DMSO (Table 1, entries 2–5). DMSO was found
to be the best choice (Table 1, entry 5). In addition, we found
that increasing the reaction temperature to 110 °C increased
the yield from 41–50 % (Table 1, entries 6–8). Next, we exam-
ined the scope of the catalyst; the addition of acids or inorganic
bases did not promote the nitrogenation reaction to form 2a
(Table 1, entries 9 and 10); however, the addition of organic
[a] Institute of Next Generation Matter Transformation, College of Chemical
Engineering and College of Materials Science at Huaqiao University,
668 Jimei Blvd., Xiamen, Fujian 361021, P. R. China
E-mail: qsong@hqu.edu.cn
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201600438.
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Communication
bases did increase the yield of 2a (Table 1, entries 11–14). In-
deed, in the presence of 40 mol-% of BnNHCH3, the best yield
of 77 % was obtained (Table 1, entry 14). Surprisingly, a
stoichiometric amount of BnNHCH3 resulted in a drop in the
yield (Table 1, entry 15). We also examined other nitrogen sour-
ces, and they all gave results that were inferior to those ob-
tained with tBuONO. From these above experiments, we deter-
mined the optimized conditions to include the use of BnNHCH3
(40 mol-%) in DMSO (1 mL) at 110 °C in air for 12 h.
Table 1. Optimization of the reaction conditions.[a]
Entry
Catalyst
Solvent
Temp. [°C]
Yield[b] [%]
1
2
3
4
–
–
–
–
CH3CN
toluene
1,4-dioxane
DMF
90
90
90
21
<1
7
90
38
5
6
7
8
9
10
1
12
13
14
15[d]
16[e]
17[f]
–
–
–
–
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
90
41
40
50
33
21
0
57
69
100
110
120
110
110
110
110
110
110
110
110
110
CH3COOH
K2CO3
DABCO
Et2NH
Et3N
BnNHCH3
BnNHCH3
BnNHCH3
BnNHCH3
51
77 (73)[c]
52
30
<1
Scheme 2. Substrate scope.
[a] Reaction conditions: 1a (0.5 mmol), tBuONO (0.9 mmol), catalyst (40 mol-
%), solvent (1 mL), in air, 12 h. DABCO = 1,4-diazabicyclo[2.2.2]octane.
[b] Yield determined by GC analysis. [c] Yield of isolated product. [d] N-Meth-
ylbenzylamine (100 mol-%) was used. [e] Isoamyl nitrite was used instead of
tBuONO. [f] TMSN3 was used instead of tBuONO.
To understand the mechanism of this reaction, various con-
trol experiments were performed. First, the reaction was totally
quenched with the addition of radical scavengers, 2,6-di-tert-
butyl-4-methylphenol
(BHT)
and
1,1-diphenylethylene
[Scheme 3, Equations (1) and (2)], which suggested that a radi-
cal process might be involved in this transformation.
With the optimized reaction conditions in hand, we began
to survey the substrate scope and limitations of the reaction
(Scheme 2). Electron-donating substituents on the aromatic
rings of the arylacetylenes, such as 4-tert-butyl, 4-methyl, 3-
methyl, methoxy, and n-pentyloxy groups, gave desired nitriles
2a and 2c–f in moderate to good yields. Desired products 2g
and 2h were obtained from 1-ethynylnaphthalene and 4-
(phenylethynyl)benzene, respectively, in good yields. To our de-
light, halo groups were well tolerated under the standard condi-
tions; desired products 2i–l were delivered in decent yields, and
they can undergo further structural manipulation. Moreover,
various electron-deficient substituents survived in this reaction,
and corresponding desired products 2m–r were obtained in
moderate yields. Gratifyingly, heteroacetylenes were also
proven to be good candidates in this transformation, and het-
erocyclic nitriles derived from pyridine and thiophene gave
products 2s and 2t in yields of 45 and 40 %, respectively.
Scheme 3. Radical trapping experiments.
To further examine which intermediates were formed, vari-
ous potential intermediates, such as benzaldehyde and phenyl-
acetaldehyde, acetophenone, phenylacetic acid and benzoyl-
formic acid, phenylacetonitrile and benzoyl cyanide, and benz-
Notably, upon employing the present reaction conditions aldehyde oxime were all tested under the standard conditions;
with internal alkynes, such as 1-phenylpropyne and diphenyl- only phenylacetaldehyde (3) afforded desired product 2a
acetylene, to our disappointment, the desired products were [Scheme 4, Equation (3)], yet it was isolated in very low yield
not obtained.
(27 %). Therefore, it is less likely that phenylacetylene is con-
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Communication
verted into phenylacetaldehyde first under the standard condi- mechanistic studies and synthetic applications are underway in
tions and then affords the nitrile.
our laboratory.
Experimental Section
General Procedure: A reaction tube was charged with the alkyne
(0.5 mmol), tBuONO (0.9 mmol, 92.7 mg, 108 μL), and BnNHCH3
(40 mol-%, 24 mg) in air. Upon completion of the reaction, saturated
sodium chloride solution (20 mL) was added, and the aqueous layer
was extracted with ethyl acetate (3 × 20 mL). The combine organic
layer was dried with anhydrous Na2SO4. The solvent was removed
under reduced pressure, and the residue was purified with flash
chromatography (silica gel).
Acknowledgments
Scheme 4. Atmospheric effects on the reactions.
Financial support from the National Natural Science Foundation
of China (NSFC) (grant number 21202049), the Recruitment Pro-
gram of Global Experts (1000 Talents Plan), Fujian Hundred Tal-
ents Program, the Natural Science Foundation of Fujian Prov-
ince (grant number 2016J01064), the Graduate Innovation Fund
of Huaqiao University (grant to Y. L.), and from the Program of
Innovative Research Team of Huaqiao University is gratefully
acknowledged. We also thank the Instrumental Analysis Center
of Huaqiao University for analysis support.
Control experiments also showed that in the absence of mo-
lecular oxygen (under N2), the reaction did not proceed at all
[Scheme 4, Equation (4)]. Interestingly, if the reaction was per-
formed under a pure oxygen atmosphere, the reaction was
rather messy, and only a small amount of nitrile was formed
with the majority of the products as benzaldehyde and benzoic
acid [Scheme 4, Equation (5)].
On the basis of the results of the control experiments as
well as literature precedent,[11] a putative reaction mechanism
is shown in Scheme 5. Initially, the addition of NO2,[11] gener-
ated in situ from tBuONO, across the carbon–carbon triple bond
of the arylacetylene gives radical intermediate A. Then, interme-
diate A isomerizes to afford B and C.[12] This is followed by
cyclization of C, which produces four-membered intermediate
D. Finally, elimination of formic acid from D leads to benzo-
nitrile.
Keywords: Synthetic methods · Cleavage reactions · C–C
activation · Alkynes · Nitriles
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Scheme 5. Proposed reaction mechanism.
Conclusion
In conclusion, we developed a metal-free method to synthesize
nitriles through cleavage of the carbon–carbon triple bonds of
arylacetylenes in air. Various functional groups were well toler-
ated in this transformation, and thus, a new and complemen-
tary method for the formation of arylnitriles is provided. Further
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Received: April 7, 2016
Published Online: ■
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Communication
Cleavage Reactions
Y. Lin, Q. Song* ................................... 1–5
Cleavage of the Carbon–Carbon
Triple Bonds of Arylacetylenes for
the Synthesis of Arylnitriles without
a Metal Catalyst
A metal-free synthesis of arylnitriles This transformation exhibits good
through cleavage of carbon–carbon functional group tolerance and pro-
triple bonds is established by using vides the corresponding nitriles in
tBuONO as the nitrogenating agent. moderate to good yields.
DOI: 10.1002/ejoc.201600438
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim