Perfluoroalkanosulfonyl fluoride: A useful reagent for dehydration of aldoximes to nitriles

Article abstract of DOI:10.1016/j.cclet.2015.11.004

The reaction of a variety of aldoximes with perfluoroalkanosulfonyl fluoride in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in dichloromethane smoothly generated the corresponding nitriles in 70%-95% yields.

Full text of DOI:10.1016/j.cclet.2015.11.004

G Model
CCLET 3480 1–3
Chinese Chemical Letters xxx (2015) xxx–xxx
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Chinese Chemical Letters
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1
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Original article
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Perfluoroalkanosulfonyl fluoride: A useful reagent for dehydration
of aldoximes to nitriles
a
a
a
b,
Q1 Zhao-Hua Yan a, , Huan Tian , Dong-Dong Zhao , Hong-Ai Jin , Wei-Sheng Tian
*
*
5
6
7
a College of Chemistry, Nanchang University, Nanchang 330031, China
b Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
A R T I C L E I N F O
A B S T R A C T
Article history:
The reaction of a variety of aldoximes with perfluoroalkanosulfonyl fluoride in the presence of 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) in dichloromethane smoothly generated the corresponding
nitriles in 70–95% yields.
Received 2 September 2015
Received in revised form 3 October 2015
Accepted 27 October 2015
Available online xxx
ß 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Keywords:
Perfluoroalkanosulfonyl fluoride
Dehydration
Aldoximes
Nitriles
1,8-Diazabicyclo[5.4.0]undec-7-ene
8
9
1. Introduction
Perfluoroalkanosulfonyl fluoride (RfSO2F, such as n-C4F9SO2F and 28
n-C8F17SO2F) is a kind of commercially available and cost effective 29
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Nitriles are versatile organic precursors in the synthesis of
amines, amides, aldehydes, carboxylic acids, esters, and ketones,
which are also key raw materials for agricultural chemicals, dyes,
pharmaceuticals, and functional materials [1]. Furthermore, the
cyano group is present in numerous bioactive molecules [2]. Two
of the most classic methods for the preparation of aliphatic nitriles
and aromatic nitriles are, respectively, the nucleophilic substitu-
tion reaction of alkyl halides with highly toxic inorganic cyanides
[3] and the Sandmeyer reactions [4]. However, the most
convenient and attractive method for the synthesis of nitriles is
the dehydration of aldoximes, owing to their easy availability and
avoiding the use of highly toxic inorganic cyanides. To date, lots of
methods have been developed to effect the conversion of
aldoximes to nitriles [5]. However, some of these methods suffer
from the use of moisture-sensitive, highly expensive, and toxic or
hazardous reagents, and some of them suffer from tedious work-
up procedure. Therefore the search for more convenient and
effective methods for dehydration of aldoximes is still desirable.
reagent. RfSO2F is non-toxic and moisture-tolerant. In RfSO2F- 30
induced reactions, the by-product is water-soluble perfluoroalk- 31
anesulfonic acid anion, which makes their work-up procedure very 32
easy to handle; on the other hand, perfluoroalkanesulfonic acid salt 33
RfSO3ÀM+ is also a kind of highly valued surfactant, and if needed, 34
perfluoroalkanesulfonic acid can be easily isolated from the aqueous 35
layer by adjusting its pH value with aqueous hydrochloric acid 36
solution after work-up procedure. On the basis of the excellent 37
leaving ability of perfluorosulfonate anion (in comparison with p- 38
toluenesulfonate anion and methanesulfonate anion) [6] and the 39
ease of reaction of perfluoroalkanosulfonyl fluoride with alcohol in 40
the presence of a base, RfSO2F has been developed and used as an 41
excellent hydroxyl group-activating reagent for fluorination of 42
alcohols [7], for cyclodehydration of chiral vicinal diols [8], N- 43
acylamino alcohols,
thioamides [9]. Very recently, perfluoroalkanosulfonyl fluoride- 45
induced Beckmann rearrangement of -unsaturated ketoximes in 46
b-hydroxy sulfonamides and b-hydroxy 44
a,b
alkaline media leading to the smooth formation of enamides was 47
reported by us [10]. However, to the best of our knowledge, the 48
reaction of perfluoroalkanosulfonyl fluoride with aldoximes has not 49
been investigated yet. Herein, we wish to report the results of 50
dehydration of aldoximes to nitriles induced by perfluoroalkano- 51
*
Corresponding authors.
sulfonyl fluoride in alkaline media (Scheme 1).
52
E-mail addresses: yanzh@ncu.edu.cn (Z.-H. Yan), wstian@sioc.ac.cn (W.-S. Tian).
http://dx.doi.org/10.1016/j.cclet.2015.11.004
1001-8417/ß 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Z.-H. Yan, et al., Perfluoroalkanosulfonyl fluoride: A useful reagent for dehydration of aldoximes to
nitriles, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.11.004

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CCLET 3480 1–3
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Z.-H. Yan et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
dehydration were investigated (entries 4–8). Among screened
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solvents of acetonitrile, toluene, chloroform, dichloromethane,
acetone and tetrahydrofuran, dichloromethane was found to be
the best choice, and the use of the other solvents resulted in lower
yields of 2a in the range of 72–90%. Several organic and inorganic
bases, such as pyridine, triethylamine, DBU, K2CO3, and NaOH were
further tested, and the results showed that the use of DBU as base
offered the best yield (entries 9–13). Finally both n-C4F9SO2F and
Scheme 1. n-C4F9SO2F-induced dehydration of aldoximes to nitriles.
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2. Experimental
Table 2
n-C4F9SO2F-Induced dehydration of a variety of aldoximes to nitriles.a
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57
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65
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The general procedure of n-C4F9SO2F-induced dehydration of a
variety of aldoximes to nitriles: at room temperature, n-C4F9SO2F
(20.0 mmol, 2.0 equiv.) was slowly dropped via syringe into a
solution of substrate 1a (10.0 mmol) and 1,8-diazabicy-
clo[5.4.0]undec-7-ene (DBU, 50.0 mmol, 5.0 equiv.) in CH2Cl2
(20 mL). The resulting solution was stirred at this temperature
for 10 min. Evaporation under vacuum to remove volatile
components offered residue which was purified through silica
gel column chromatography (eluted with a mixture of petroleum
ether and ethyl acetate), generating nitrile 2a in 95% yield.
Entry
1
Substrate
Product
Yield (%)b
95
2
3
4
5
6
80
82
89
88
80
Colorless solid, mp 143–146 8C. 1H NMR (400 MHz, CDCl3):
(d, 2H, J = 8.0 Hz), 7.88 (d, 2H, J = 8.0 Hz); 13C NMR (101 MHz,
CDCl3): 150.01, 133.43, 124.26, 118.31, 116.74.
d 8.35
d
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3. Results and discussion
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To optimize the reaction conditions, p-nitrobenzaldoxime (1a)
was selected as
a model substrate under various reaction
conditions (Table 1). First, using dichloromethane as solvent and
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as base, we explored
the effect of the molar ratio of n (1a): n (n-C4F9SO2F): n (DBU) on
dehydration at room temperature. When the molar ratio of 1a/n-
C4F9SO2F/DBU is 1:1.5:2, the yield of 2a is 46% with 40% of 1a
recovered after 10 min (Table 1, entry 1); the longer reaction time
did not improve the yield of 2a. When the ratio was increased to
1:2:5, the best result was obtained with the formation of 2a in 95%
yield (entry 3). When the reaction was carried out at 0 8C, a similar
result was obtained; however when the reaction was run at reflux,
some unidentified impurities formed. Solvent effects on
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70
79
8
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Table 1
Optimization of reaction conditions.a
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80
.
Entry
Solvent
Base (equiv.)
Yield (%)b
1c
2
CH2Cl2
CH2Cl2
CH2Cl2
THF
DBU (2)
DBU (4)
DBU (5)
DBU (5)
DBU (5)
DBU (5)
DBU (5)
DBU (5)
Et3N (5)
Pyridine (5)
K2CO3 (5)
NaOH (5)
Et3N (5)
DBU (5)
46
84
95
82
90
76
87
72
68
16
–
12
13
70
86
3
4
5
CHCl3
6
MeCN
7
PhCH3
CH3COCH3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3COCH3
CH2Cl2
8
9d
10
11
12
13
14e
14
71
88
12
56
92
15
a
Reactions were run at room temperature for 10 min,
n (1a): n (n-
C4F9SO2F) = 1:2.
b
Isolated yields.
c
a
n (1a): n (n-C4F9SO2F) =1:1.5.
Reaction was run at r.t. for 24 h.
RfSO2F is n-C8F17SO2F.
n (1): n (n-C4F9SO2F): n (DBU) = 1:2:5, and the reaction was run at room
d
e
temperature in CH2Cl2 for 10 min.
b
Isolated yields.
Please cite this article in press as: Z.-H. Yan, et al., Perfluoroalkanosulfonyl fluoride: A useful reagent for dehydration of aldoximes to
nitriles, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.11.004

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Z.-H. Yan et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
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(b) M.A. Cohen, J. Sawden, N.J. Turner, Selective hydrolysis of nitriles under mild 127
conditions by an enzyme, Tetrahedron Lett. 31 (1990) 7223–7226.
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n-C8F17SO2F showed imilar activity (entry 14). Therefore, the
optimized reaction conditions for the dehydration of 1a are:
CH2Cl2 as solvent, DBU as base, n (1a): n (n-C4F9SO2F): n
(DBU) = 1:2:5, room temperature, and reaction time of 10 min.
With the optimized reaction conditions in hand, a variety of
aldoximes were subjected to the n-C4F9SO2F/DBU system for
dehydration to explore the scope and limitations of the reaction.
The results are presented in Table 2. All the aldoximes were
smoothly converted to the corresponding nitriles in 70–95% yields.
The dehydration of pyridine-3-carbaldehyde oxime provided 3-
cyanopyridine in 86% yield (entry 13). For comparison, the
dehydration of pyridine-3-carbaldehyde oxime with AlCl3Á6H2O/
KI/H2O/CH3CN system [11] and triphenylphosphine/I2 system [12]
provided 3-cyanoprridine in 69% yield (after refluxing at 80 8C for
6 h) and in 84% yield (at room temperature for 4 h), respectively.
The method is applicable to aromatic, aliphatic, and heteroaryl
aldoximes and is tolerant to a wide range of functional groups such
as methoxy, hydroxyl, halide, and diethylamino groups. Electron-
donating or electron-withdrawing group on the aromatic ring has
little effect on the yield of the product. The work-up procedure is
simple, just needing evaporation under vacuum to remove volatile
components and subsequent purification of residue through silica
gel column chromatography with a mixture of petroleum ether
and ethyl acetate as eluent. All the products were confirmed by 1H
NMR and 13C NMR, IR and MS spectra, and the data were identical
with literature records.
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In conclusion, an efficient method was developed for the
dehydration of aldoximes in alkaline media and nitrile products
were obtained in 70–95% yields. Mild reaction conditions, simple
work-up procedure, and high yields are advantages of the presented
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Acknowledgment
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The authors thank the National Natural Science Foundation of
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Please cite this article in press as: Z.-H. Yan, et al., Perfluoroalkanosulfonyl fluoride: A useful reagent for dehydration of aldoximes to
nitriles, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.11.004