A practical iodine-catalyzed oxidative conversion of aldehydes to nitriles

Article abstract of DOI:10.1039/c6ra26435b

A simple and efficient method for the direct synthesis of nitriles from aldehydes using ammonium acetate as the nitrogen source has been developed. The reactions were performed with iodine as the catalyst and tert-butyl hydroperoxide (TBHP) as the oxidant under mild conditions. A variety of aromatic, heteroaromatic, aliphatic and allylic aldehydes could be converted into their corresponding nitriles in good to excellent yields.

Full text of DOI:10.1039/c6ra26435b

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A practical iodine-catalyzed oxidative conversion
of aldehydes to nitriles†
Cite this: RSC Adv., 2017, 7, 1484
Chaojie Fang, Meichao Li,* Xinquan Hu, Weimin Mo, Baoxiang Hu, Nan Sun, Liqun Jin
and Zhenlu Shen*
A simple and efficient method for the direct synthesis of nitriles from aldehydes using ammonium acetate as
the nitrogen source has been developed. The reactions were performed with iodine as the catalyst and tert-
butyl hydroperoxide (TBHP) as the oxidant under mild conditions. A variety of aromatic, heteroaromatic,
aliphatic and allylic aldehydes could be converted into their corresponding nitriles in good to excellent
yields.
Received 7th November 2016
Accepted 20th December 2016
DOI: 10.1039/c6ra26435b
www.rsc.org/advances
efficient and manageable oxidant, giving tert-butanol as the
benign by-product in most cases. Recently, the I /TBHP system
2
Introduction
Nitriles are important starting materials for the synthesis of has been widely used in oxidative reactions, such as C–C bond
45
1
–3
4,5
6,7
8,9
10,11
43
44
amides, amines, ketones, carbonic acids and esters.
Furthermore, the cyano group is a key motif in the structure of and oxidative cyclization, etc. Reddy and co-workers reported
numerous useful compounds, such as bioactive natural prod- a KI/I –TBHP system for the conversion of alcohols, aldehydes
cleavage, oxidation of indoles, oxidative coupling reaction
46
47
2
12,13
14
ucts, pharmaceuticals
and functional materials. Tradition- and amines into nitriles. Under this catalytic system, they
15
16
ally, the Sandmeyer and Rosenmund–von Braun reaction were prepared a series of aromatic nitriles from aromatic aldehydes
widely used in synthesizing aryl nitriles, while highly toxic by using ammonia as the nitrogen source in water. However, the
cyanide salts, were always required and the reactions produced yields of products were general low and the nitro-substituted
large amounts of inorganic salts as waste. Therefore, the devel- substrate cannot be converted into the desired product.
opment of new pathways for the synthesis of nitriles has gained What's more, the large excess of ammonia may cause environ-
increasing attention. In the past decades, a large number of new mental problems as a result of its easy volatility and would be an
methods utilizing different kinds of compounds, like alco- undesirable contaminant in waste water.
17–21
22–25
26–28
29,30
hols,
amines,
amides
and aldoximes
as starting
Ammonium acetate (NH OAc), which has many remarkable
4
materials have been reported. These methods offer great advantages, including good stability and low toxicity, is an idea
improvements, but always need high temperature or pressure, low-cost alternative nitrogen source instead of ammonia.
stoichiometric or excess amount of highly reactive oxidants, Previously, ammonium acetate as the cyanide source has
transition metal catalysts or metal complex catalysts.
already been developed in the direct synthesis of nitriles from
Aldehydes have been utilized as attractive starting materials aldehydes, like NH OAc/HTIB and NH OAc/PPTB systems.
4 4
48
49
for the synthesis of nitriles due to their ready availability, and One of limitations of these examples is the use of expensive
several methods have been reported with different compounds halogen-containing oxidants, which could generate hazardous
31–42
as nitrogen sources.
Inevitably, there were some drawbacks
existing in these methods: (i) high reaction temperature was
still needed; (ii) stoichiometric halogen-containing or metal
oxidants were always required; (iii) limited substrate scopes; (iv)
transition metal catalysts were essential in most cases.
Metal-free catalysis in modern organic synthesis has received
2
much attention because of its economy and low toxicity. The I /
tert-butyl hydroperoxide (TBHP) catalytic oxidation system is
one of the most popular examples. TBHP is a kind of mild,
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou
3
10014, China. E-mail: zhenlushen@zjut.edu.cn; limc@zjut.edu.cn
†
Electronic supplementary information (ESI) available: Experimental procedure
Scheme 1 The improved method for the synthesis of nitriles from
1
and copies of H NMR spectra. See DOI: 10.1039/c6ra26435b
aldehydes with NH
4
OAc as a nitrogen source.
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wastes during work-up. On the other hand, about decade times
When the loading of Na
2
CO
3
was reduced to 1.0 equiv. and
of NH OAc had to be employed to ensure the full conversion of 0.5 equiv., the reaction time had to be prolonged to 2.5 h and
4
aldehydes, which is extremely wasteful.
8 h, respectively (entries 13 and 14). Thus, we chose to add 1.0
Inspired by hereinbefore work, as a part of our research equiv. of Na CO into the reaction system. When the loading of
2
3
program aimed at synthesis of nitriles and I
2
-catalyzed reac-
2
I was reduced to 2.5 mol%, 1b could be obtained in 99% yield
50–52
tion,
we attempted to develop a simple, efficient, econom- in 5 h (entry 15). Aer that, the reaction temperature was
ical and environmentally friendly method for the direct decreased and we found that 1b could be obtained in 99% yield
ꢀ
synthesis of nitriles from aldehydes using NH
4
OAc as the at 50 C in 5.5 h (entries 17 and 18). At last, when the loading of
nitrogen source under I /TBHP system (Scheme 1).
2
4
NH OAc was reduced to 1.5 equiv., 1a could also be converted
into 1b successfully with high yield in 6 h (entry 19).
Having dened the optimum conditions for the reaction, the
substrate scope of this methodology was investigated and the
Results and discussion
At the outset, benzaldehyde (1a) was chosen as the model results are summarized in Scheme 2. Initially, the catalytic
substrate to examine a variety of reaction condition parameters system was examined to tolerate a wide range of aromatic alde-
and the results are summarized in Table 1. Firstly, a series of hydes which bearing electron-withdrawing or electron-donating
solvents were screened and the results indicated 1a could be groups on benzene ring. It was observed that substrates
transformed to benzonitrile (1b) in 86% yield in ethanol within carrying electron-withdrawing groups could be smoothly con-
ꢀ
8
h at 60 C (entry 4). As is known to all, water is an ideal solvent. verted into the desired products in 5 h (2b–9b). Benzaldehydes
We have also tried to verify the feasibility of using water as the carrying electron-donating groups, need much more time to
solvent. Unfortunately, the easy formation of amide in aqueous complete their transformation (10b–17b). The I –TBHP catalytic
medium resulted in a low yield of nitrile (35%) (entry 8). Then system was also tolerant of substrates containing heteroatoms
.5 equiv. of K CO as acid-binding agent was tentatively added such as oxygen, sulfur and nitrogen. In the case of 20a and 22a,
2
1
2
3
into the reaction, and 1a was almost completely converted into the conversions could perform smoothly in 5 h (20b and 22b).
b in 2.5 h (entry 9). Some other acid-binding agents, such as However, in the case of electron-rich heteroaromatic aldehydes
NaHCO , NaOAc, Na CO
(entries 10–12), were also tested. containing N and S atoms, prolonged time was needed for full
Gratifyingly, the reaction could be performed more smoothly in conversions (19b and 21b). In addition, the representative
1
3
2
3
the presence of Na
2
CO
3
(entry 12).
a
Table 1 Optimization of I
2
–TBHP catalytic system for the direct synthesis of benzonitrile from benzaldehyde
NH
(equiv.)
4
OAc
I
2
Addictive
(equiv.)
ꢀ
b
Entry
(mol%)
Solvent
CH CN
T ( C)
t (h)
Yield (%)
1
2
3
4
5
6
7
8
9
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.5
1.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
2.5
1.0
2.5
2.5
2.5
2.5
3
—
—
—
—
—
—
—
—
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
50
40
50
50
8.0
8.0
8.0
8.0
8.0
8.0
8.0
8.0
2.5
7.0
4.0
1.5
2.5
8.0
5.0
12.0
5.5
11.0
6.0
12.0
72
14
25
86
25
70
37
35
98
96
99
99
99
94
99
94
99
94
98
90
PhCH
PhCl
3
2 5
C H OH
THF
DMF
EtOAc
2
H O
C
C
C
C
C
C
C
C
C
C
C
C
2
H
5
H
5
H
5
H
5
H
5
H
5
H
5
H
5
H
5
H
5
H
5
H
5
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
K
2
CO
NaOAc (1.5)
NaHCO (1.5)
3
(1.5)
10
11
12
13
14
15
16
17
18
19
20
2
2
2
2
2
2
2
2
2
2
2
3
Na
2
Na
2
Na
2
Na
2
Na
2
Na
2
Na
2
Na
2
Na
2
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
(1.5)
(1.0)
(0.5)
(1.0)
(1.0)
(1.0)
(1.0)
(1.0)
(1.0)
a
b
Reaction conditions: 1a (4 mmol, 0.424 g), 5 mL of solvents, 1.1 equiv. of TBHP. Yields were determined by GC using an internal standard
method.
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there was a competitive relationship between the halogenated
reaction and the desired reaction.
With this encouraging nding in hand, some other a-
unsaturated aldehydes, such as undecanal (25a), helional (26a)
and N-Boc-piperidin-4-ylformaldehyde (27a) were also exam-
ined in this modied method. To our delight, all of them could
be converted into the desired nitriles with satisfying yields. At
last, two allylic aldehydes, cinnamaldehyde (28a) and (E)-2-
methyl-3-phenylacrylaldehyde (29a) also tolerated our catalytic
system. Cinnamonitrile (28b) could be obtained in 80% yield
under optimized and modied conditions.
In addition, this catalytic system could also be applied in the
synthesis of a complex compound (30b) (eqn (1)), which
displays appreciable anti-inammatory and selective COX-2
51
inhibitory activity. Because of the poor solubility of 30a in
ethanol, equal volume of DMF was chosen as the solvent in the
transformation of 30a to 30b. To our delight, the reaction was
smoothly performed and 84% yield of 30b was obtained.
(1)
In order to examine the practicability of this catalytic system,
gram-scale reaction was also performed under the optimized
conditions (14.8 g of 4-bromobenzaldehyde (7a)). It was grati-
fying that the isolated product 13.5 g of 4-bromobenzonitrile
(7b) could be obtained (93% yield).
Next, we envisioned oxidative conversion of primary alcohol to
nitrile using our method (eqn (2)). However, the oxidative
conversion of benzyl alcohol under the optimized conditions
gave only 1b in 58% yield aer 24 h although the loading of TBHP
was increased to 2.5 equiv. A large amount of benzyl alcohol was
remained, which cannot be converted into the desired product.
a
a
Scheme 2 Oxidative conversion of aldehydes to nitriles . Reaction
conditions: aldehyde (4 mmol), NH
4
OAc (1.5 equiv.), I
2
(2.5 mol%),
ꢀ
TBHP (1.1 equiv.), 5 mL of ethanol, 50 C. Y ¼ yield of the isolated
(2)
b
product. Yields were determined by GC using an internal standard
c
method. Aldehyde was slowly added into reaction solution.
With these results in hand, we tried to explore the plausible
reaction mechanism. When 4 mmol of benzaldehyde (1a), 1.5
polycyclic substrate, 1-naphthaldehyde (18a) tolerated our cata-
lytic system to give the product 18b in excellent yield.
Adamantane-1-carbaldehyde (23a), an a-saturated aliphatic
aldehyde, gave the desired nitrile 23b in 94% yield. As is known
to all, aldehydes with a-H atoms can be halogenated at their
4 2 3
equiv. of NH OAc, 1.0 equiv. of Na CO and 5 mL of ethanol were
ꢀ
mixed up and stirred under 50 C for 8 h, phenylmethanimine
was achieved in 13% yield determined by GC with the normali-
zation method. Then 2.5 mol% of I
added into the reaction mixture, it was founded that benzonitrile
1b) was the sole product aer 6 h. These results implied that: (i)
2
and 1.1 equiv. of TBHP were
a positions by reaction with halogens, like Cl
conclusion was proved by the representative aliphatic aldehyde
-phenylpropanal (24a). When it was used as the substrate, the
2 2 2
, Br and I . This
(
3
phenylmethanimine was the intermediate product; (ii) the
process of transformation phenylmethanimine into 1b could
promote the generation of phenylmethanimine from 1a.
yield of 3-phenylpropanenitrile (24b) was very low. However,
when aldehyde 24a was slowly added into the reaction solution,
60% yield of 24b could be obtained. This consequence suggested
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(
2 3
6 mmol) of ammonium acetate, 0.424 g (4 mmol) of Na CO ,
2
5.4 mg (0.1 mmol) of I , 0.61 g of TBHP (wt% ¼ 65%, 1.1
2
equiv.) and 5 mL of ethanol. Then the ask was sealed by
a rubber plug and placed into a preheated oil bath (50 C).
ꢀ
Aer that, 4 mmol of aldehyde, which was distilled to 1 mL
with ethanol, was injected into the solution slowly (4 h). The
work-up procedure was as same as that for the synthesis of
1
b–24b.
Benzonitrile (1b). Colorless oil; H NMR (500 MHz, CDCl
Scheme 3 A plausible reaction mechanism.
1
3
)
d 7.66–7.63 (m, 2H), 7.62–7.59 (m, 1H), 7.49–7.46 (m, 2H); MS:
+
m/z ¼ 103.0 [M ].
According to literatures and our observations, a plausible
4
-Nitrobenzonitrile (2b). Pale yellow solid; mp: 146.3–
reaction mechanism of this I /TBHP catalytic system has been
2
1
ꢀ
1
7
48.7 C; H NMR (500 MHz, CDCl
3
) d 8.39–8.36 (m, 2H), 7.91–
proposed in Scheme 3. First of all, aldehyde reacted with
ammonium acetate to form aldimine 3 and sodium acetate in
the presence of Na CO . Then aldimine 3 was oxidized by I ,
2 3 2
affording N-iodo aldimine 4 as an intermediate, which was
+
.90 (m, 2H); MS: m/z ¼ 148.0 [M ].
-Fluorobenzonitrile (3b). White solid; mp: 32.7–34.1 C; H
ꢀ
1
4
NMR (500 MHz, CDCl
3
) d 7.71–7.67 (m, 2H), 7.21–7.16 (m, 2H);
+
MS: m/z ¼ 121.0 [M ].
transformed into nitrile 2 by b-elimination of HI under alkaline
ꢀ
1
ꢁ
4-Chlorobenzonitrile (4b). White solid; mp: 93.1–94.7 C; H
condition. At the same time, I was oxidized to I by TBHP,
2
NMR (500 MHz, CDCl ) d 7.62–7.60 (m, 2H), 7.50–7.47 (m, 2H);
3
which was reduced to tert-butanol immediately.
+
MS: m/z ¼ 137.0 [M ].
ꢀ
1
3-Chlorobenzonitrile (5b). White solid; mp: 44.0–45.8 C; H
Conclusion
NMR (500 MHz, CDCl
3
) d 7.65 (t, J ¼ 1.7 Hz, 1H), 7.61–7.59 (m,
1
H), 7.58–7.56 (m, 1H), 7.45 (t, J ¼ 15.8 Hz, 2H); MS: m/z ¼ 137.0
In conclusion, we have successfully developed a simple and
efficient method for the direct synthesis of nitriles from alde-
hydes with ammonium acetate as the nitrogen source, using I
as the catalyst and TBHP as the oxidant. This catalytic system is
practical, environmentally friendly as it utilizes ethanol as
solvent and TBHP as oxidant. A broad range of substrates
including aromatic, heteroaromatic, aliphatic and allylic
nitriles could be obtained in good to excellent yields.
+
[M ].
ꢀ
1
2-Chlorobenzonitrile (6b). White solid; mp: 37.5–40.3 C; H
2
NMR (500 MHz, CDCl ) d 7.70–7.68 (m, 1H), 7.58–7.52 (m, 2H),
3
+
7
.41–7.38 (m, 1H); MS: m/z ¼ 137.0 [M ].
ꢀ
4
-Bromobenzonitrile (7b). White solid; mp: 109.6–112.4 C;
1
H NMR (500 MHz, CDCl ) d 7.66–7.64 (m, 2H), 7.55–7.53 (m,
3
+
2
H); MS: m/z ¼ 180.9 [M ].
-(Triuoromethyl)benzonitrile (8b). White solid; mp: 40.6–
4
ꢀ
1
42.8 C; H NMR (500 MHz, CDCl
3
) d 7.82–7.81 (d, 2H, J ¼ 8.1
+
Experimental section
General procedure for the synthesis of 1b–23b, 29b and 30b
Hz), 7.76 (d, 2H, J ¼ 8.3 Hz); MS: m/z ¼ 171.1 [M ].
ꢀ
Methyl 4-cyanobenzoate (9b). White solid; mp: 60.0–61.5 C;
H NMR (500 MHz, CDCl ) d 8.16–8.14 (m, 2H), 7.77–7.75 (m,
1
3
To a 20 mL, two-necked, round-bottom ask equipped with
a magnetic stirring bar and a thermometer, were added 4 mmol
of aldehyde, 0.462 g (6 mmol) of ammonium acetate, 0.424 g (4
mmol) of Na CO , 25.4 mg (0.1 mmol) of I , 0.61 g of TBHP (wt%
+
2
H), 3.97 (s, 3H); MS: m/z ¼ 161.1 [M ].
1
4
-Methylbenzonitrile (10b). Colorless oil; H NMR (500 MHz,
CDCl
3
) d 7.54 (d, 2H, J ¼ 8.2 Hz), 7.27 (d, 2H, J ¼ 8.0 Hz), 2.42 (s,
2
3
2
+
3H); MS: m/z ¼ 117.1 [M ].
¼
65, 1.1 equiv.) and 5 mL of ethanol (replaced by 5 mL of DMF
for 30a). Then the ask was sealed by a bubbler and placed into
1
3-Methylbenzonitrile (11b). Colorless oil; H NMR (500 MHz,
CDCl
3
) d 7.44 (d, J ¼ 6.5 Hz, 2H), 7.40 (d, J ¼ 7.6 Hz, 1H), 7.36–
ꢀ
a preheated oil bath (50 C). Aer the reaction was nished (as
determined by GC, except 30a which was determined by HPLC),
to the reaction mixture were added 10 mL of 5% of Na S O
2 2 3
solution and stirred for 15 min. Then the mixture was trans-
ferred into a separation funnel, and 100 mL of diethyl ether
+
7.33 (m, 1H); MS: m/z ¼ 117.1 [M ].
1
2-Methylbenzonitrile (12b). Colorless oil; H NMR (500 MHz,
CDCl ) d 7.56 (d, J ¼ 7.7 Hz, 1H), 7.48–7.45 (m, 2H), 7.30 (d, 1H, J
3
¼
7.8 Hz), 7.26 (t, 1H, J ¼ 14.8 Hz), 2.53 (s, 1H); MS: m/z ¼ 117.1
+
[
M ].
(replaced by 100 mL of dichloromethane for 30b) were also
ꢀ
4
-Methoxybenzonitrile (13b). White solid; mp: 58.2–60.3 C;
added to the separation funnel. The two-phase mixture was
1
3
H NMR (500 MHz, CDCl ) d 7.60–7.58 (m, 2H), 6.97–6.94 (m,
washed with saturated sodium bicarbonate solution (25 mL ꢂ
+
2
H), 3.86 (s, 3H); MS: m/z ¼ 133.0 [M ].
2 4
2). Then the organic layer was dried with Na SO , concentrated
3
,4-Dimethoxybenzonitrile (14b). White solid; mp: 64.9–
on a rotary evaporator and the residue was puried by column
chromatography on silica gel using hexanes/EtOAc as eluent to
afford the pure product.
1
ꢀ
6
1
6.4 C; H NMR (500 MHz, CDCl ) d 7.30–7.28 (m, 1H), 7.09 (d,
H, J ¼ 1.9 Hz), 6.90 (d, 2H, J ¼ 8.3 Hz), 3.91 (s, 3H), 3.88 (s, 3H);
3
+
MS: m/z ¼ 163.1 [M ].
4
-(Methylthio)benzonitrile (15b). White solid; mp: 59.7–
General procedure for the synthesis of 24b–28b
ꢀ
1
62.2 C; H NMR (500 MHz, CDCl ) d 7.55–7.53 (m, 2H), 7.28–
3
+
To a 20 mL, two-necked, round-bottom ask equipped with 7.26 (m, 2H), 2.52 (s, 3H); MS: m/z ¼ 149.0 [M ].
a magnetic stirring bar and a thermometer, were added 0.462 g
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1
4
-(tert-Butyl)benzonitrile (16b). Pale yellow oil; H NMR (500 Science Foundation of Zhejiang Province (LY17B060007), and
MHz, CDCl
) d 7.61–7.59 (m, 2H), 7.51–7.48 (m, 2H), 1.34 (s, Hangzhou Qianjiang Distinguished Experts Project.
H); MS: m/z ¼ 159.1 [M ].
-(Diethoxymethyl)benzonitrile (17b). Colorless oil; H NMR
3
+
9
1
4
Notes and references
(
3
500 MHz, CDCl
3
) d 7.60 (dd, J ¼ 24.0, 7.4 Hz, 1H), 5.51 (s, 1H),
+
.61–3.49 (m, 4H), 1.21 (t, 6H, J ¼ 6.6 Hz); MS: m/z ¼ 205.1 [M ].
1 A. R. Katritzky, B. Pilarski and L. Urogdi, Synthesis, 1989,
949–950.
1
1
-Naphthonitrile (18b). Pale yellow oil; H NMR (500 MHz,
CDCl ) d 8.24–8.22 (m, 1H), 8.07 (d, J ¼ 8.3 Hz, 1H), 7.93–7.89
2 J. Borau-Garcia, D. V. Gutsulyak, R. J. Burford and
W. E. Piers, Dalton Trans., 2015, 44, 12082–12085.
3 C. Battilocchio, J. M. Hawkins and S. V. Ley, Org. Lett., 2014,
16, 1060–1063.
4 F. Gould, G. Johnson and A. Ferris, J. Org. Chem., 1960, 25,
1658–1660.
5 H. Adkins and H. R. Billica, J. Am. Chem. Soc., 2002, 1948(70),
695–698.
6 W. B. Jang, W. S. Shin, J. E. Hong, S. Y. Lee and D. Y. Oh,
Synth. Commun., 2006, 27, 3333–3339.
7 M. Ortiz-Marciales, L. M. Tirado, R. Colon, M. L. Ufret,
R. Figueroa, M. Lebron, M. DeJesus, J. Martinez and
T. Malave, Synth. Commun., 1998, 28, 4067–4075.
8 D. Brady, N. Dube and R. Petersen, S. Afr. J. Sci., 2006, 102,
339–344.
3
(
m, 2H), 7.70–7.67 (m, 1H), 7.63–7.60 (m, 1H), 7.53–7.50 (m,
+
1
H); MS: m/z ¼ 153.0 [M ].
-Bromothiophene-2-carbonitrile (19b). Pale yellow oil;
NMR (500 MHz, CDCl
) d 7.39 (d, J ¼ 4.0 Hz, 1H), 7.10 (d, J ¼
.0 Hz, 1H); MS: m/z ¼ 188.9 [M ].
-Bromofuran-2-carbonitrile (20b). Pale orange oil; H NMR
1
5
H
3
+
4
1
5
(
1
500 MHz, CDCl ) d 7.07 (d, J ¼ 3.6 Hz, 1H), 6.49 (d, J ¼ 3.6 Hz,
3
+
H); MS: m/z ¼ 171.0 [M ].
N-Boc-3-indolecarbonitrile (21b). White solid; mp: 119.3–
ꢀ
1
1
8
21.1 C; H NMR (500 MHz, CDCl
3
) d 8.20 (d, J ¼ 8.3 Hz, 1H),
.13 (s, 1H), 7.74 (d, J ¼ 7.9 Hz, 1H), 7.47–7.44 (m, 1H), 7.41–7.38
+
(m, 1H), 1.71 (s, 9H); MS (ESI): m/z ¼ 265.1 [M + Na ].
1
Benzofuran-2-carbonitrile (22b). Yellow oil; H NMR (500 MHz,
CDCl ) d 7.70 (d, J ¼ 7.9 Hz, 1H), 7.59–7.57 (m, 1H), 7.55–7.51 (m,
3
+
1
H), 7.48 (d, J ¼ 7.9 Hz, 1H), 7.40–7.37 (m, 1H); MS: m/z ¼ 143.0 [M ].
9 J. Raj, N. Singh, S. Prasad, A. Seth and T. C. Bhalla, Acta
Microbiol. Immunol. Hung., 2007, 54, 79–88.
Adamantane-1-carbonitrile (23b). White solid; mp: 185.2–
ꢀ
1
1
1
91.2 C; H NMR (500 MHz, CDCl
.76–1.70 (m, 6H); MS: m/z ¼ 161.1 [M ].
3
) d 2.04 (d, J ¼ 6.2 Hz, 9H), 10 T. Kamitanaka, K. Yamamoto, T. Matsuda and T. Harada,
+
Tetrahedron, 2008, 64, 5699–5702.
1
3
-Phenylpropanenitrile (24b). Pale yellow oil; H NMR (500 11 M. Noe, A. Perosa and M. Selva, Green Chem., 2013, 15, 2252–
MHz, CDCl
3
) d 7.39–7.36 (m, 2H), 7.32–7.29 (m, 1H), 7.27–7.25
2260.
(
¼
m, 2H), 2.96 (t, J ¼ 7.4 Hz, 2H), 2.62 (t, J ¼ 7.4 Hz, 2H); MS: m/z 12 D. J. Augeri, J. A. Robl, D. A. Betebenner, D. R. Magnin,
+
131.1 [M ].
K. Ashish, J. G. Robertson, W. Aiying, L. M. Simpkins,
1
Dodecanenitrile (25b). Colorless oil; H NMR (500 MHz, CDCl )
T. Prakash and H. Qi, J. Med. Chem., 2005, 48, 5025–5037.
3
d 2.33 (t, J ¼ 7.1 Hz, 2H), 1.66–1.62 (m, 2H), 1.47–1.41 (m, 2H), 1.29– 13 E. Pascual, F. Sivera, U. Yasothan and P. Kirkpatrick, Nat.
+
1
.27 (m, 12H), 0.87 (t, J ¼ 7.0 Hz, 3H); MS: m/z ¼ 162.1 [M ].
Rev. Drug Discov., 2009, 8, 191–192.
1
1
,3-Benzodioxole-5-propanenitrile (26b). Pale yellow oil; H 14 H. Jiang, X. Yang, Z. Cui, Y. Liu, H. Li, W. Hu, Y. Liu and
NMR (500 MHz, CDCl
3
) d 6.77 (d, J ¼ 7.9 Hz, 1H), 6.72 (d, J ¼
D. Zhu, Appl. Phys. Lett., 2007, 91, 123505, DOI: 10.1063/
1.2784970.
15 D. T. Mowry, Chem. Rev., 1948, 42, 189–283.
1
1
.6 Hz, 1H), 6.69–6.67 (m, 1H), 5.93 (s, 2H), 2.85–2.73 (m, 3H),
.31 (d, J ¼ 6.7 Hz, 3H); MS: m/z ¼ 189.1 [M ].
+
1
N-Boc-4-piperidinecarbonitrile (27b). Colorless oil; H NMR 16 G. P. Ellis and T. M. Romney-Alexander, Chem. Rev., 1987, 87,
(
1
500 MHz, CDCl ) d 3.68–3.31 (m, 4H), 2.82–2.77 (m, 1H), 1.90–
779–794.
3
+
.75 (m, 4H), 1.45 (s, 9H); MS: m/z ¼ 209.2 [M ].
17 S. U. Dighe, D. Chowdhury and S. Batra, Adv. Synth. Catal.,
2014, 356, 3892–3896.
1
Cinnamonitrile (28b). Pale yellow oil; H NMR (500 MHz,
CDCl
3
) d 7.47–7.39 (m, 6H), 5.89 (d, J ¼ 16.7 Hz, 1H); MS: m/z ¼ 18 R. V. Jagadeesh, H. Junge and M. Beller, Nat. Commun., 2014,
+
129.0 [M ].
5, 4123, DOI: 10.1038/ncomms5123.
1
a-Methylcinnamonitrile (29b). Pale yellow oil; H NMR (500 19 W. Yin, C. Wang and Y. Huang, Org. Lett., 2013, 15, 1850–
MHz, CDCl ) d 7.43–7.42 (m, 2H), 7.40–7.38 (m, 1H), 7.35–7.34
1853.
3
(
¼
m, 2H), 7.23 (d, J ¼ 0.5 Hz, 1H), 2.16 (d, J ¼ 1.6 Hz, 3H); MS: m/z 20 D.-W. Tan, J.-B. Xie, Q. Li, H.-X. Li, J.-C. Li, H.-Y. Li and
+
143.1 [M ].
-(4-Cyano-3-(p-tolyl)-1H-pyrazol-1-yl)benzenesulfonamide
J.-P. Lang, Dalton Trans., 2014, 43, 14061–14071.
21 T. Oishi, K. Yamaguchi and N. Mizuno, Angew. Chem., Int.
Ed., 2009, 48, 6286–6288.
4
1
(
6
30b). White solid; H NMR (500 MHz, DMSO-d ) d 9.55 (s, 1H),
8
8
(
.15 (d, J ¼ 8.8 Hz, 2H), 8.02 (d, J ¼ 8.8 Hz, 2H), 7.90 (d, J ¼ 22 L. Gao, H. Tang and Z. Wang, Chem. Commun., 2014, 50,
.1 Hz, 2H), 7.51 (s, 2H), 7.41 (d, J ¼ 8.0 Hz, 2H), 2.40 (s, 3H); MS
4085–4088.
+
ESI): m/z ¼ 360.3 (M + Na) .
23 K. M. Lambert, J. M. Bobbitt, S. A. Eldirany, K. B. Wiberg and
W. F. Bailey, Org. Lett., 2014, 16, 6484–6487.
2
4 A. F. Shoair and A. A. El-Bindary, Spectrochim. Acta, Part A,
014, 131, 490–496.
This work was nancially supported by the National Natural 25 D. Damodara, R. Arundhathi and P. R. Likhar, Adv. Synth.
Science Foundation of China (21376224, 21206147), the Natural Catal., 2014, 356, 189–198.
Acknowledgements
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