An efficient and versatile synthesis of aromatic nitriles from aldehydes

Article abstract of DOI:10.1016/j.cclet.2012.10.006

A simple and direct method has been developed for synthesis of nitriles based on one-pot reaction of aromatic aldehydes with three different kind of reagents: CeCl₃·7H₂O/KI/H₂O₂, CeCl₃·7H₂O/KI/UHP and (NH₄) ₂Ce(NO₃)₆/KI/H₂O₂ in aqueous ammonia.

Full text of DOI:10.1016/j.cclet.2012.10.006

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 1323–1326
www.elsevier.com/locate/cclet
An efficient and versatile synthesis of aromatic nitriles
from aldehydes
a,
Maryam Hajjami , Arash Ghorbani-Choghamarani ,
a
*
b
Mohammad Ali Zolfigol , Fatemeh Gholamian
a
a
Department of Chemistry, Faculty of Science, Ilam University, P.O. Box 69315516, Ilam, Iran
b
Faculty of Chemistry, Bu-Ali Sina University, P.O. Box 6517838683, Hamadan, Iran
Received 15 May 2012
Available online 16 November 2012
Abstract
A simple and direct method has been developed for synthesis of nitriles based on one-pot reaction of aromatic aldehydes with
three different kind of reagents: CeCl Á7H O/KI/H , CeCl Á7H O/KI/UHP and (NH Ce(NO /KI/H in aqueous ammonia.
3
2
2
O
2
3
2
4
)
2
3
)
6
2 2
O
#
2012 Maryam Hajjami. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Nitrile; Cerium chloride; Ammonium cerium nitrate; Urea hydrogen peroxide; Hydrogen peroxide
Nitriles are useful intermediate for the synthesis of amines, amides, carboxylic acids and esters. The conversion of
aldehydes into the corresponding nitriles is an important functional group transformation in organic chemistry [1].
Many methods involve the initial conversion of aldehydes to aldimines, by condensation with aqueous ammonia
and then oxidative conversion of aldimines into nitriles are known [2–5]. Aldehydes may also be converted into their
respective nitriles using NH OHÁHCl and the mechanism involves aldoxime generation, and dehydration of aldoxime
2
to give nitriles [6–8]. Although several methods are known for the transformation of aldehydes to their corresponding
nitriles, many drawbacks such as low yields, expensive or commercially unavailable reagents and laborious work-up
procedures limit the use of some of these procedures.
Despite these, there is still scope for alternative reagent systems for the preparation of nitriles from aldehydes.
Based on these facts, we decided to evaluate the simple one-pot conversion of aldehydes into nitriles using three
different systems: CeCl Á7H O/KI in the presence of hydrogen peroxide or urea hydrogen peroxide (UHP) in aq.
3
2
ammonia and (NH ) Ce(NO ) /KI in the presence of hydrogen peroxide in aq. ammonia.
4
2
3 6
Here, as a part of our study for the functionalization of organic compounds [9–12], we would like to report for the
direct synthesis of nitriles from aldehydes using three different oxidative systems (Scheme 1). In this light, a variety of
aromatic aldehydes were transformed to nitriles smoothly via a combination of an oxidizing agent (H O or UHP) and
2
2
CAN/KI or CeCl Á7H O/KI for in situ generation of I in aq. ammonia. The results for this transformation summarized
3
2
2
in Table 1.
*
Corresponding author.
E-mail address: mhajjami@yahoo.com (M. Hajjami).
1001-8417/$ – see front matter # 2012 Maryam Hajjami. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2012.10.006

1324
M. Hajjami et al. / Chinese Chemical Letters 23 (2012) 1323–1326
Aor Bor C
RCHO
RCN
o
aq.NH , rt or 60 C
3
A= CAN/KI/H O
2
2
B=CeCl .7H O/KI/H O
3
2
2
2
C=CeCl .7H O/KI/UHP
3
2
Scheme 1. Direct conversion of aldehydes into nitriles.
All nitriles synthesis reactions were performed in a sealed tube and conversion of aldehydes indicated by TLC.
To show the effect of potassium iodide (KI), the reaction of 4-methoxybenzaldehyde (as representative sample)
using CAN/H O , CeCl Á7H O/H O or CeCl Á7H O/UHP in aq. ammonia was examined in the absence of KI.
2
2
3
2
2
2
3
s
Surprisingly the reaction did not occur after specific time for both three systems (entry 2, Table 1).
Entry 4, Table 1 illustrates the role of cerium reagent in system B. as the result show the reaction did not happen
after 240 min and impurity of aldimine was observed.
Also, the effect of hydrogen peroxide in outcome of reaction was examined via doing reaction in the absence of
H O . For this reason, the conversion of 4-bromobenzaldehyde was performed using mixtures containing 3 mmol of
2
2
CeCl Á7H O, KI (1.8 mmol) in aq. NH (3 mL) at 60 8C (entry 5, Table 1). After 240 min, the conversion to nitrile did
3
2
3
not occur and impurity of aldimine was observed.
Proposed mechanism for these transformations is outlined in Scheme 2. Initially aldehyde reacts with ammonia to
form an imine, which further reacts with iodine (which generated in situ in the reaction condition) to form N-
iodoaldimine, which eventually oxidized into corresponding nitrile.
Table 1
Oxidative conversion of aldehydes to the corresponding nitriles with CAN/KI/H
aqueous NH at 60 8C.
2
O
2
(A), CeCl
3
Á7H
2
2
O/KI/H O
2
(B) and CeCl
3
2
Á7H O/KI/UHP (C) in
3
a
Entry Substrate
Reagent:KI
A/B/C
Time (min)
A/B/C
Yeild (%)
A/B/C
mp (8C) (observed)
A/B/C
mp (8C) (reported) Ref.
b
b
120/240/240 82 /84 /90
b
1
2:1/3:1.5/2:1
2:–/3:–/2:–
57–58/57–59/56–58
59
[13]
–
OHC
OCH3
OCH3
Br
c
2
120/240/240 No reaction
–
–
OHC
3
2.5:1.2/3:1.8/3:1.5 180/240/240 88/88/98
109–111/109–12/97–99
110–111
[1]
–
OHC
d,f
–/No reaction /–
4
–/–:1.8/–
–/3:1.8/–
–/240/–
–/240/–
–
–
–
–
OHC
Br
e,f
–/No reaction /–
5
–
OHC
Br
Cl
6
2.5:1.2/3:1.8/3:1.5 180/240/240 90/95/74
89–93/91–93.5/87–89
94
[13]
[14]
OHC
b
2.5:1.2/3:1.5/2:1.3 180/240/240 82/90 /91
7
OMe
62–63.5/61–63/62.5–63.5 62.5
OHC
OMe
b
2.5:1.2/3:1.5/3:1.5 180/240/240 56/81 /71
8
Oil/Oil/Oil
Oil
[1]
OHC
b
180/240/240 80/84 /78
9
3:1.5/3:1.5/3:1.5
26–27.5/26.5–28/26–28
32.5–34/–/–
25
[15]
[1]
OHC
Me
F
g
2.5:1.2/3:1.8/3:1.5 180/240/240 73/– /–
g
1
0
33–35
OHC
a
b
c
d
e
f
Isolated yield.
Reaction performed at room temperature.
In the absence of KI.
In the absence of CeCl Á7H
3
2
O.
2 2
In the absence of H O .
Impurity of aldimine was observed.
g
Reaction did not complete and impurity observed.

M. Hajjami et al. / Chinese Chemical Letters 23 (2012) 1323–1326
1325
CAN, H O
2
2
or
2
KI
I
2
CeCl .7H O,H O or UHP
3
2
2 2
aq. NH3
RCHO
RCH=NH
H
R
-HI
RCH=NH
I
2
C N
I
RCN
Scheme 2. Mechanism of the conversion of aldehydes into nitriles.
In conclusion, we have accomplished new, efficient and mild systems A, B and C for the synthesis of nitriles from
aldehydes in aq. ammonia. The advantages of the present method are the operational simplicity, generality of the
reactions, readily available reagents, good to excellent yields with both three systems.
1
. Experimental
Chemicals were purchased from Fluka, Merck and Aldrich chemical companies. The known products were
1
13
characterized by comparison of their spectral ( H NMR, and C NMR) and physical data with those of authentic
samples.
To a mixture of aldehyde (1 mmol) and aq. ammonia (3 mL), CAN/KI or CeCl Á7H O/KI in hydrogenperoxide
3
2
(
3 mL) or CeCl Á7H O/KI in urea hydrogen peroxide (3 mmol) was added. The resulting mixture was stirred in
3
2
sealed tube at room temperature or 60 8C. After completion of the reaction, the reaction mixture was diluted with
water and Na S O (5 mmol) was added. Finally product extracted with dichloromethane (20 mL) and organic
phase dried over Na SO (3 g). After evaporation of dichloromethane, corresponding nitrile was obtained in good
2
2 3
2
4
yield.
Selected spectroscopy data: 4-Methoxybenzonitrile: IR (KBr, n cm ): 2218, 1606, 1458, 1258, 1176, 831; H
À1
1
1
NMR (400 MHz, CDCl ): d 7.53 (d, 2H, J = 8.4 Hz), 6.91 (d, 2H, J = 8.4 Hz), 3.82 (s, 3H); C NMR (100 MHz,
3
3
À1
CDCl ): d 162.9, 133.9, 119.2, 114.8, 103.8, 55.6. 4-Bromobenzonitrile: IR (KBr, n cm ): 2218, 1606, 1458, 1258,
3
1
176, 831; H NMR (400 MHz, CDCl ): d 7.53 (d, 2H, J = 8.4 Hz), 6.91 (d, 2H, J = 8.4 Hz), 3.82 (s, 3H); C NMR
13
1
3
À1
(
100 MHz, CDCl ): d 162.9, 133.9, 119.2, 114.8, 103.8, 55.6. 3,4-Dimethoxybenzonitrile: IR (KBr, n cm ): 2224,
3
1
599, 1463, 1244; H NMR (400 MHz, CDCl ): d 7.06 (s, 1H), 6.88 (s, 1H), 6.71 (s, 1H), 3.72 (s, 3H), 3.69 (s, 3H);
13
1
NMR (100 MHz, CDCl ): d 152.7, 148.9, 126.2, 119.1, 113.7, 111.1, 103.5, 55.9. 4-Methylbenzonitrile: H NMR
C
3
1
3
1
(
400 MHz, CDCl ): d 7.47 (d, 2H, J = 7.6), 7.23 (d, 2H, J = 7.6), 2.37 (s, 3H). 4-Flourobenzonitrile: H NMR
3
1
400 MHz, CDCl ): d 7.69–7.66 (m, 2H), 7.19–7.15 (m, 2H); C NMR (100 MHz, CDCl ): d 166.3, 163.7, 134.8,
3
(
3
3
1
35.7, 118.6, 117, 116.7, 108.6, 108.5.
Acknowledgments
The authors acknowledge Ilam University, Ilam, Iran, and Bu-Ali Sina University Research Council (No. 32-1716)
for financial support of this work.
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