Polyethylene glycol supported phosphorus chloride: An efficient and recyclable catalyst for the preparation of nitriles from aldoximes

Article abstract of DOI:10.1080/10426507.2016.1266357

Polyethylene glycol (PEG) supported phosphorus chloride has been developed and used as an efficient and recyclable catalyst for dehydration of various aldoximes into the corresponding nitriles. This protocol has many advantages such as high conversion, high selectivity, short reaction time, mild reaction conditions, and simple experimental procedure.

Full text of DOI:10.1080/10426507.2016.1266357

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POLYETHYLENE GLYCOL SUPPORTED PHOSPHORUS CHLORIDE: AN EFFICIENT
AND RECYCLABLE CATALYST FOR THE PREPARATION OF NITRILES FROM
ALDOXIMES
1
2,*,#
2
2
Xiao-Lan Zhang , Shou-Ri Sheng , Mei-Hong Wei , and Xiao-Ling Liu
College of Chemistry and Chemical Engineering, Shangrao Normal University, Shangrao
34000, P. R. China
1
3
2
College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022,
P. R. China
#
Address correspondence to Shou-Ri Sheng; E-mail: shengsr@jxnu.edu.cn
*
Financial support from the National Natural Science Foundation of China (No. 21062007), the
Opening Foundation of National Research Center for Carbohydrate Synthesis (No.
GJDTZX-KF-201414), the Opening Foundation of Key Laboratory of Functional Small Organic
Molecule, Ministry of Education (No. KLFS-KF-201411) and the Research Program of Jiangxi
Province Department of Education (No. GJJ11380) is gratefully acknowledged.
Abstract
Polyethylene glycol (PEG) supported phosphorus chloride has been developed and used as an
efficient and recyclable catalyst for dehydration of various aldoximes into the corresponding
nitriles. This protocol has many advantages such as high conversion, high selectivity, short
reaction time, mild reaction conditions, and simple experimental procedure.
1
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Graphical Abstract
PEG-OPC2l
R CH=N OH
R CN
3
2
MS 4 A / CH Cl2
4
Keywords
PEG-supported phosphorus chloride; nitrile; aldoxime; dehydration; catalytic synthesis
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INTRODUCTION
Nitriles are important synthetic intermediates for pharmaceuticals, pesticides, dyes, and
1
–3
material sciences.
Moreover, the nitrile group is a versatile functional group in organic
synthesis and can be easily transformed into a variety of groups such as acids, esters, aldehydes,
4
,5
amines, amides, imidoesters, benzamidines and nitrogen-containing heterocycles. The classical
6
methods for the preparation of nitriles include Kolbe nitrile synthesis, ammoxidation of
7
8
9
aldehydes, hydrocyanation of alkenes, Sandmeyer reaction of diazonium salts, and
1
0
Rosenmund–von Braun reaction of aryl halides. In recent years, numerous methods for their
1
1
synthesis have been reported in the literature, such as the metal-catalyzed cyanation of aryl
1
2
13,14
15
16
halides, dehydration of amides
or oximes, Schmidt reaction of aldehydes, oxidation of
1
7
18
azides and alcohols. Among these, the dehydration of oximes into nitriles is one of the most
suitable and attractive strategies for the preparation of nitriles owing to the availability of starting
material and the avoidance of very toxic cyanide ion. To date, many different reagents and
19–30
conditions have been established for the dehydration of aldoximes to give nitriles.
Although
many of these methods possess synthetic value, the search for a simple, rapid, mild,
environmentally friendly, and universally applicable synthetic strategy for the conversion of
aldoximes into nitriles is still an attractive subject. In the past years, there has been a
considerable growth in interest in the use of soluble polymer-supported catalysts and reagents in
organic synthesis because of their low cost, easy of preparation, simple workup and recoverablity
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3
1–33
of catalysts.
Polyethylene glycol (PEG), as a inexpensive polymer, is an ideal soluble support
since it is soluble in many organic solvents, such as CH Cl , DMF, toluene or CH OH at room
2
2
3
temperature and can be precipitated from a solution by addition of diethyl ether, tert-butyl
3
4
methyl ether, hexane or propan-2-ol. Furthermore, the PEG-bound products can be adequately
1
35
characterized by using routine analytical techniques such as TLC, IR and H NMR. Herein, we
present our efforts to develop a novel facile method for the preparation of nitriles from
aldoximes using PEG-supported phosphorus chloride as an efficient and recyclable catalyst
under mild conditions. To the best of our knowledge, the conversion of aldoximes into nitriles
using this new reagent has not been reported.
RESULTS AND DISCUSSION
By considering the solubility profile and loading capacity of the polymer derivatives,
commercially available dihydroxy functionalised polyethylene glycol (PEG) of average
molecular weight 4000 was chosen as the polymer support for the synthetic protocol. As shown
in Scheme 1, the phenol was attached to the PEG 4000 support by esterification of PEG with
4
4
-hydroxybenzoic acid in the presence of 1,3-dicyclohexylcarbodiimide (DCC) and
-(dimethylamino)pyridine (DMAP) in anhydrous CH Cl at room temperature for 24 h.
2
2
Subsequently, the PEG-supported phenol (PEG-OC H -OH-p) 1 was converted to phosphorus
6
4
chloride 2 by treating with excess phosphorus trichloride. The reaction went to completion over
5
h and gave the corresponding PEG-supported phosphorus chloride (PEG-OPCl ) 2 after the
2
4
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release of hydrogen chloride gas. The reaction mixture was then isolated by addition of degassed
diethyl ether into the reaction mixture, followed by filtration and sequential washing of the
polymeric precipitate with diethyl ether to afford the reagent 2 in 95 % yield, based on the
1
weight of polymer isolated. The progress of the PEG supported reaction was monitored by H
1
NMR and IR analysis. The H NMR spectra of PEG-bound 1 and 2 were presented Figure 1,
which indicated the conversion of terminal hydroxyl groups on PEG to be complete and
quantitative. In addition, the aromatic protons of PEG-OC H -OH-p 1 appearing at 7.80 and 6.80
6
4
ppm shifted to 7.69 and 6.89 ppm respectively after condensation with phosphorus trichloride.
Besides, the IR spectra of PEG, PEG-bound 1 and 2 were shown in Figure 2. The complete
–
1
–1
disappearance of the hydroxyl stretch at 3426 cm plus the disappearance bands of 1280 cm as
–1
well as the appearance of weak P–Cl band absorption at 585 cm , indicated the PEG-OPCl 2
2
formation. The loading capacity of 2 was calculated by elemental analyses and found to be 0.90
mmol Cl/g.
With the PEG attached phosphorus chloride 2 in hand, the viability and efficiency of the
dehydration reactions of aldoximes catalyzed by this new regent was explored. To optimize the
reaction conditions, a model reaction of benzaldehyde oxime with the catalyst 2 to afford
benzonitrile was investigated and the results are summarized in Table 1. Several solvents
including polar and non-polar solvents were tested for the reaction. From the results in Table 1,
it is evident that some solvents such as DMSO, MeCN, THF and CH Cl are all applicable for
2
2
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this conversion. Considering the ease of product separation, CH Cl was selected to be the
2
2
solvent of choice. Additionally, after further varying the other reaction conditions such as
amount of catalyst, reaction temperature and time, the better result for this conversion was
conveniently achieved in 92 % yield through the dehydration reaction of benzaldehyde oxime in
the presence 20 mol % of PEG-OPCl in CH Cl at refluxing temperature (entry 6). Interestingly,
2
2
2
it was found that the reaction rate and selectivity could be significantly increased when the
reaction was carried out in the presence of molecular sieves (4 Å, 2 weight equiv to oxime)
(entry 9). It should be pointed out that the reaction was complete within 30 min in the presence
of molecular sieves while it took 1 h to achieve a full conversion in the absence of molecular
sieves (entries 6–8), whereas no conversion was observed by the action of molecular sieves alone
(10 weight equiv to oxime) without the catalyst 2 even after 24 h under reflux.
The plausible mechanism of the nitrile formation is depicted in Scheme 3. For the synthesis of
nitriles, 4Å molecular sieves were used to absorb the water produced in the conversion of
aldoximes into the corresponding nitriles and prevent the hydrolysis of the catalyst 2.
To explore the generality and scope of this method, the optimized reaction conditions were
applied to a variety of aldoximes. As can be observed from Table 2, it is clear that this catalyst
system of PEG-OPCl /molecular sieves is highly efficient and useful for aromatic (entries 1–15)
2
and aliphatic aliphatic (entries 19 and 20) aldoximes. Excellent results were obtained for aryl
aldoximes with different substituents at the meta and/or para positions; relatively low yields of
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nitriles were obtained for ortho-substituted aromatic aldoximes (entries 6, 8 and 11–12) and the
reaction time needs to be slightly prolonged, probably owing to the stereo-hindrance effect of the
ortho-substituted groups. It should be noted that trans-cinnamaldoxime was also conveniently
converted to the corresponding nitrile in good yield with stereochemical retention of the double
bond (entry 18). Besides, various heteroaromatic aldoximes turned out to be compatible with the
employed reaction conditions (entries 16 and 17). Furthermore, a substrate bearing bis-aldoxime
was also uneventfully dehydrated to give 1,4-dicyanobenzene in excellent yield (entry 21).
As depicted in Table 2, the recovery and reuse of PEG-OPCl catalyst was examined by
2
considering the model reaction under the same conditions (entries 1–4). After the completion of
the reaction, the PEG-OPCl was precipitated from the reaction mixture with dried diethyl ether
2
for the subsequent run of the reaction. The efficiency of the PEG-OPCl catalyst on the
2
dehydration of benzaldoxime 3a was maintained up to four runs in this case, and then it took
slightly longer to get a complete conversion. Meanwhile, the yield of the product 4a slight
decreased gradually.
In summary, a new PEG-supported phosphorus chloride catalyst has been prepared, and has
been employed here for the first time as an efficient dehydration agent for the conversion of the
wide range of aldoximes to the corresponding nitriles. This protocol has many advantages such
as the availability and reusability of this dehydration agent, high efficiency and selectivity, as
well as mild reaction conditions, short reaction times, and simple work-up procedure. The further
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application based on PEG-supported phosphorus chloride is currently underway.
EXPERIMENTAL
Melting points were determined with an X melting point apparatus and were not corrected.
4
1
The H NMR spectra were recorded with a Bruker Avance (400 MHz) spectrometer, using
CDCl as the solvent and TMS as an internal standard. The FTIR spectra were measured with a
3
Perkin-Elmer SP One FTIR spectrophotometer. Mass spectra (EI, 70eV) were recorded on a
HP5989B mass spectrometer. Aldoximes 3a–3r were prepared from hydroxylamine
2
6
hydrochloride with the corresponding aldehydes by standard methods. The other chemicals
were obtained from commercial suppliers and used without purification.
Preparation of PEG-supported Phosphorus Chloride (PEG-OPCl ) 2
2
4-Hydroxybenzoic acid (1.38 g, 10 mmol), 1,3-dicyclohexylcarbodiimide (DCC) (2.06 g, 10
mmol) and 4-(dimethylamino)pyridine (DMAP) (305 mg, 2.5 mmol) were added to PEG (5g, 2.5
mmol) in CH Cl (20 mL) and the mixture was stirred at room temperature for 24 h. The
2
2
precipitate was removed by filtration and the filtrate was diluted with i-PrOH (200 mL). CH Cl
2
2
o
was removed under reduced pressure and the residue was cooled to –10 C. The white precipitate
was collected and washed several times with i-PrOH and Et O. After drying in vacuum, the
2
1
PEG-bound phenol 1 was obtained as white powder. H NMR (400 MHz, CDCl ): δ = 8.34 (s, 1
3
H), 7.80 (d, J = 8.0 Hz, 2 H), 6.80 (d, J = 8.0 Hz, 2 H), 3.82–3.47 (m, PEG backbone,
–
1
OCH CH O); IR (KBr): ν = 3365, 2990, 1680, 1500, 1342, 1242, 1100, 827 cm .
2
2
max
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To phosphorus trichloride (10 mL) in a three-necked flask equipped with a condenser, the
above PEG-bound phenol 1 was added in portions under stirring. HCl gas was gradually released
from the reaction vessel. After the addition, the mixture was stirred for 5 h at room temperature.
Then, excess phosphorus trichloride was evaporated off and the crude product was dissolved in
CH Cl (20 mL). After this, diethyl ether (200 mL) was added to the mixture with vigorous
2
2
o
stirring, and then cooled to –10 C. The resulting precipitate was collected by filtration, washed
with diethyl ether (3 × 20 mL) and then dried under high vacuum to give the desired PEG-OPCl2
1
2
as a white solid (5.3 g, 95.5 % based on polymer recovery). H NMR (400 MHz, CDCl ): δ =
3
7
.69 (d, J = 8.4 Hz, 2 H), 6.89 (d, J = 8.4 Hz, 2 H), 3.81–3.46 (m, PEG backbone, OCH CH O);
2
2
–
1
IR (KBr): νmax = 2992, 1682, 1502, 1342, 1243, 1113, 828, 585 cm . The catalyst loading
capacity was determined by elemental analysis to be about 0.90 mmol Cl/g.
Preparation of Nitriles (4a–4r): General Procedure
To a stirred solution of aldoxime 3 (1.0 mmol) in CH Cl (5 mL) was added PEG-OPCl
2
2
2
(0.20 mmol, 220 mg) and molecular sieves 4 Å (2 wt equiv to aldoxime), the reaction mixture
stirred at refluxing temperature for the given time in Table 2. After completion of the reaction
(TLC), diethyl ether (100 mL) was added to the reaction mixture with vigorous stirring and then
o
cooled to 0 C. The recovered white precipitate, along with molecular sieves 4 Å was collected
by filtration, washed with cold diethyl ether (2 × 20 mL) for reuse. The combined filtrate was
concentrated in a rotary evaporator, and the residue was purified by through a pad of silica gel
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column (10–20 % ethyl acetate in hexane) to give pure product, which was characterized by
1
13,14, 16, 18, 26, 28, 30
comparison of its IR and H NMR spectra or melting point with published
1
13
values. The analytical data for the obtained products 4a–4r are together with their H and C
NMR spectra are presented in the Supplemental Materials (Figures S 1 – S 36)
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a
Table 1. Catalytic conversion of benzaldehyde oxime to benzonitrile
b
Entry
Solvent
MeCN
THF
Time
4 h
Yield (%)
1
2
3
4
5
78
86
90
89
90
92
90
92
98
3 h
DMF
3 h
PhCH
3 h
3
CH
CH
CH
CH
CH
Cl
2.5 h
1 h
2
2
2
2
2
2
2
2
2
2
c
6
Cl
Cl
Cl
Cl
d
7
1 h
e
8
1 h
f
9
30 min
a
Benzaldehyde oxime (1.0 mmol), PEG-OPCl (220 mg, 0.20 mmol), solvent (5 mL)
2
b
c
Isolated yield
At refluxing temperature
d
PEG-OPCl (170 mg, 0.15 mmol) was used under refluxing temperature without additional
2
molecular sieves
e
PEG-OPCl (275 mg, 0.25 mmol) was used under refluxing temperature without additional
2
molecular sieves
f
The reaction was carried out in the presence of PEG-OPCl (220 mg, 0.20 mmol) and molecular
2
sieves (4 Å, 2 weight equiv to aldoxime) under refluxing temperature.
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a
Table 2. PEG-OPCl catalytic dehydration of various aldoximes to nitriles
2
Yield (%)
b
Entry Substrate (3)
Time (min) Nitrile (4)
c
1
2
3
4
Benzaldehyde oxime (3a)
30
30
35
40
4a
4a
4a
4a
98
d
d
d
e
Benzaldehyde oxime (3a)
Benzaldehyde oxime (3a)
Benzaldehyde oxime (3a)
94
f
93
g
90
4
-Methoxybenzaldehyde oxime
3b)
-Methylbenzaldehyde oxime
3c)
-Methylbenzaldehyde oxime
3d)
-Hydroxybenzaldehyde
3e)
-Hydroxybenzaldehyde
3f)
5
6
7
8
9
35
40
30
45
40
4b
4c
4d
4e
4f
98
84
97
85
95
(
2
(
3
(
2
oxime
oxime
(
4
(
1
1
0
1
4-Chlorobenzaldehyde oxime (3g)
2-Chlorobenzaldehyde oxime (3h)
30
40
4g
4h
92
84
2
,4-Dichlorobenzaldehyde oxime
3i)
-Bromobenzaldehyde
3j)
4-Nitrobenzaldehyde oxime (3k)
1
2
45
4i
82
(
4
oxime
1
1
3
4
30
45
4j
94
91
(
4k
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1
1
1
1
1
2
2
5
6
7
8
9
0
1
3-Nitrobenzaldehyde oxime (3l)
2-Furaldehyde oxime (3m)
2-Thenaldehyde oxime (3n)
Cinnamaldehyde oxime (3o)
Phenylacetaldehyde oxime (3p)
Heptaldehyde oxime (3q)
45
35
35
35
30
40
30
4l
4m
4n
4o
4p
4q
4r
93
90
95
85
92
87
97
Terephthalaldehyde oxime (3r)
a
Reaction of aldoxime (1.0 mmol) in CH Cl (5 mL) at refluxing temperature in the presence of
2
2
PEG-OPCl (220 mg) and molecular sieves 4 Å (2 wt equiv to aldoxime)
2
b
All products are known compounds, and were characterized by comparison of their mp, IR and
1
H NMR data with those of authentic samples
c
Isolated yield
d
No additional molecular sieves were added during the recycles
e
PEG-OPCl was used for the 2nd run
2
f
PEG-OPCl was used for the 3rd run
2
g
PEG-OPCl was used for the 4th run.
2
16
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1
Figure 1. H NMR spectra of PEG-C H OH-p (a) and PEG-OPCl (b).
6
4
2
17
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Figure 2. IR spectra of PEG (a), PEG-C H OH-p (b) and PEG-OPCl (c).
6
4
2
18
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HOOC
OH
HO PEG OH
HO
COO PEG OOC
OH
DCC, DMAP, CHCl
2
2
dihydroxy-PEG
MW = 4000
1
PCl3
Cl PO
2
O PEG O
OPCl2
OPCl2
2
Scheme 1. Preparation of PEG-supported phosphorus chloride 2.
19
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PEG-OPC2l
R CH=N OH
R CN
3
2
MS 4 A / CH Cl2
4
Scheme 2. PEG-OPCl catalyzed conversion of aldoximes to nitriles.
2
20
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OPCl2
R
N
R
N
OH
P O
O
P O
R CH=N OH
H
H
Cl
Cl
HCl
Cl
OH HCl
O P
Cl
OPCl2
+
H O
2
R
N
Scheme 3. Possible mechanism of the nitrile formation.
21
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