A facile and efficient one-pot synthesis of nitriles from aldehydes using hypervalent iodine(III) reagents in aqueous ammonium acetate

Article abstract of DOI:10.1055/s-0030-1258162

A facile procedure for the direct oxidation of aldehydes to the corresponding nitriles using either the hypervalent iodine(III) reagent PhI(OAc)₂ or a polymer-supported hypervalent iodine(III) reagent poly{4-[bis(acetoxy)iodo]}styrene as oxidant is reported. The oxidation proceeded in water at 70C in the presence of sodium dodecylsulfate using ammonium acetate as nitrogen source. The reaction was complete in four hours for the oxidation of benzylic and allylic aldehydes, and gave more than 90% yield in most cases. For the oxidation of aliphatic aldehydes, moderate to excellent yields of nitriles were also obtained after prolonged reaction times. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1258162

PAPER
3121
A Facile and Efficient One-Pot Synthesis of Nitriles from Aldehydes Using
Hypervalent Iodine(III) Reagents in Aqueous Ammonium Acetate
O
C
xidation of Ald
h et riles njie Zhu, Lei Ji, Yunyang Wei*
School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, P. R. of China
Fax +86(25)84317078; E-mail: ywei@mail.njust.edu.cn
Received 8 April 2010; revised 12 May 2010
On the other hand, hypervalent iodine reagents have re-
cently received much attention for their mild and highly
chemoselective oxidizing properties.16 For example,
Abstract: A facile procedure for the direct oxidation of aldehydes
to the corresponding nitriles using either the hypervalent iodine(III)
reagent PhI(OAc) or a polymer-supported hypervalent iodine(III)
2
reagent poly{4-[bis(acetoxy)iodo]}styrene as oxidant is reported. widely used pentavelent iodine reagents such as Dess–
The oxidation proceeded in water at 70 °C in the presence of sodi- Martin periodinane (DMP) and its precursor 2-iodoxy-
um dodecylsulfate using ammonium acetate as nitrogen source. The
benzoic acid (IBX) are widely known as mild and highly
reaction was complete in four hours for the oxidation of benzylic
selective reagents for the oxidation of alcohols. However,
and allylic aldehydes, and gave more than 90% yield in most cases.
these iodine(V) reagents are potentially explosive and the
For the oxidation of aliphatic aldehydes, moderate to excellent
regenerated iodine(III) species from the oxidations are
yields of nitriles were also obtained after prolonged reaction times.
usually not utilized. Thus, readily available and stable io-
Key words: aldehydes, hypervalent iodine, nitriles, oxidations,
dine(III) oxidants such as bis(acetoxy)iodobenzene and
polymers
iodosobenzene is attracting much attention. Recently,
Akamanchi and co-workers have reported a mild proce-
dure for the direct oxidative conversion of aldehydes into
The conversion of aldehydes into the corresponding ni-
triles is an important functional group transformation both
in laboratory synthesis and industrial production due to
the extensive use of nitrile compounds in synthetic chem-
17
nitriles using IBX in aqueous ammonia. To the best of
our knowledge, there is no report on the use of hyperval-
ent iodine(III) reagents as oxidants for the preparation of
nitriles.
1
istry. Moreover, cyanides play a crucial role because they
In a continuation of our interest in exploring systems for
the oxidation of organic compounds,18 here, we would
like to report a facile procedure for the direct oxidation of
can be easily converted into a variety of functional groups
2
such as acids, amides, ketones, oximes and amines. Nu-
merous methods involving aldoxime dehydration in a
two-step process have been traditionally employed to ac-
aldehydes to the corresponding nitriles with PhI(OAc) in
2
3
the presence of catalytic amounts of sodium dodecylsul-
complish this transformation. Direct conversion of alde-
fate (SDS) using NH OAc as the nitrogen source
hydes into nitriles without isolation of nitrogen-
4
4
(Scheme 1).
containing intermediates has also been explored. Of
those one-pot preparative methods developed in recent
years, the use of ammonia combined with an appropriate
oxidant, such as the systems of NH /O /CuCl ·H O/MeO-
PhI(OAc)2, SDS
RCHO
RCN
aq NH4OAc, 70 °C
3
2
7
2
2
5
6
8
Na, NH /Pb(OAc) , NH /I /MeONa, NH /S /NaNO ,
3
4
3
2
3
8
2
Scheme 1 Oxidation of aldehydes by PhI(OAc) /SDS in aqueous
ammonium acetate
2
9
10
11
12
NH /H O /CuCl, NH /I , NH /CAN, NH /NBS, or
3
2
2
3
2
3
3
1
3
NH /TBHP/KI(I ), is considered to be an expedient
3
2
method for this transformation. However, volatile ammo-
nia has an undesirable smell and is harmful to the environ-
ment. In addition, ammonia is a common contaminant in
waste water and biomass cultivation media. The adverse
effects of ammonia have promoted the development of
Initial experiments were carried out using 4-chlorobenzal-
dehyde as a model substrate. First, a range of hypervalent
iodine reagents, such as: PhIO, PhI(OCOCF ) , PhICl ,
3
2
2
PhIO or PhI(OAc) were used as oxidant in the reaction
2
2
at 50 °C, however, all of them were unsatisfactory except
1
4
various techniques for its removal. Previously, ammoni-
um acetate has also been developed as a good cyanide
source in the system of ammonium acetate and molecular
for PhI(OAc) (Table 1, entries 1–5). Ammonium salts
2
other than NH OAc could also be used as nitrogen source,
4
but lower yields were obtained (Table 1, entries 6–8).
When the reaction was allowed to proceed at different
temperatures, an optimal yield of 84% was obtained at
1
5
iodine. One of the limitations of this procedures is the re-
quirement to use more than stoichiometric amounts of io-
dine, which could lead to the generation of large amounts
of salt as a by-product during work-up.
7
0 °C (Table 1, entries 5 and 9–11). However, addition of
ZnO or 3 Å molecular sieves to accelerate the dehydration
of aldimine, which is formed in situ, to nitrile in the reac-
tion medium had no obvious advantage (Table 1, entries
SYNTHESIS 2010, No. 18, pp 3121–3125
x
x.
x
x
.
2
0
1
0
1
2 and 13). Use of acetonitrile as a co-solvent to dissolve
Advanced online publication: 07.07.2010
DOI: 10.1055/s-0030-1258162; Art ID: F06510SS
Georg Thieme Verlag Stuttgart · New York
the aldehyde and PhI(OAc) also did not improve the re-
2
©

3
122
C. Zhu et al.
PAPER
action (Table 1, entry 14). It is well known that in aque- also oxidized efficiently without any observable reaction
ous-phase reactions, addition of surfactants can improve at the double bond functionality. Even for the oxidation of
the reactions by solubilization or micelle formation ef- 2-furaldehyde, a heterocyclic aldehyde, excellent yield
fects. In order to improve the yield and selectivity of the was also obtained (Table 1, entry 9). The electronic prop-
oxidation of aldehydes, we examined the effects of a vari- erties of the substituents in the aromatic ring had a re-
ety of anionic, cationic and nonionic surfactants (Table 1, markable influence on the rate of the oxidation of
entries 15–19). Among the surfactants examined, sodium aldehydes. Strong electron-withdrawing groups, such as
dodecylsulfate (SDS), an anionic surfactant, was found to nitro groups, improve the oxidation of the aldehyde
be the most effective. The reaction proceeded faster and (Table 2, entry 4). Strong electron-donating groups, such
the yields of nitriles were remarkably increased by addi- as a methoxy group, lowered the reaction rate (Table 2,
tion of SDS to the reaction mixture. In the presence of 20 entry 6). This differs from previously reported procedures
mol% SDS, the reaction was complete within four hours where the presence of methoxy groups favors aldehyde
at 70 °C with 100% conversion of the reactant and about oxidation.1 Additionally, steric effects had only a rela-
1,13
9
5% isolated yield of the corresponding 4-chlorobenzoni- tively minor influence on the oxidation of aldehydes
trile (Table 1, entry 19).
(Table 2, entries 4 and 5). It is worth mentioning that, to-
gether with the good results obtained with benzylic alco-
hols, the yields obtained from the oxidation of aliphatic
aldehydes under the same conditions were also quite high
after prolonged reaction times (Table 2, entries 10–12). In
view of the fact that the oxidation of aliphatic aldehydes
is much more difficult than that of benzylic aldehydes, the
In order to evaluate the versatility of this novel catalytic
system, we applied the procedure to the oxidation of a
wide range of aldehydes. As shown in Table 2, most alde-
hydes underwent oxidation to afford the corresponding ni-
triles in excellent yield. Benzylic aldehydes underwent
smooth oxidation (Table 2, entries 1–7). Allylic alde-
hydes, such as cinnamyl aldehyde (Table 1, entry 8), were
Table 1 Oxidation of 4-Chlorobenzaldehydea
Entry
Oxidant
NH3
Temp (°C)
50
Additive
Yield (%)b
1
2
3
4
5
6
7
8
9
PhIO
NH OAc
–
–
4
PhI(OCOCF3)2
PhIO2
NH OAc
50
–
–
4
NH OAc
50
–
27
–
4
PhICl2
NH OAc
50
–
4
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
NH OAc
50
–
58
19
–
4
NH Cl
50
–
4
NH HCO
50
–
4
3
HCOONH4
50
–
34
16
84
76
77
80
82
88
25
63
52
95
NH OAc
r.t.
70
–
4
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
9
NH OAc
–
4
NH OAc
90
–
4
NH OAc
70
ZnO
4
NH OAc
70
3 Å MS
MeCN
TBAB
TEBACc
Tween80c
CTABc
SDS
4
NH OAc
70
4
NH OAc
70
4
NH OAc
70
4
NH OAc
70
4
NH OAc
70
4
1
NH OAc
70
4
a
Reaction conditions: 4-chlorobenzaldehyde (1 mmol), PhI(OAc) (2 mmol), aq NH OAc (3 mL, 30 mmol), additive (0.2 mmol), 70 °C, 5 h,
2
4
unless otherwise noted.
b
GC yield.
c
TEBAC = benzyltriethylammonium chloride; Tween80 = sorbitan monooleate ethoxylate; CTAB = hexadecyltrimethylammonium bromide.
Synthesis 2010, No. 18, 3121–3125 © Thieme Stuttgart · New York

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Oxidation of Aldehydes to Nitriles
3123
results obtained in the present procedure were also satis- recovered by precipitation from diethyl ether, filtration
factory.
from the reaction medium, and regeneration by treatment
with peracetic acid. The polymer was successfully recy-
cled three times (Table 2, entry 1).
We then modified this system by using a polymer-sup-
ported hypervalent iodine(III) reagent to develop a practi-
cal and clean procedure for the oxidation of aldehydes. A plausible mechanism for this reaction is depicted in
Poly{4-[bis(acetoxy)iodo]}styrene (PBAIS) has recently Scheme 2. First, the aldehyde reacts with NH OAc to
4
attracted much attention because of its similar reactivity to form an aldimine, which then undergoes oxidation by
PhI(OAc) but with the additional advantages of simple PhI(OAc) to afford N–I(OAc)Ph aldimine. Elimination
2
2
19
workup procedure and easy recovery and recycling. The of PhI and HOAc from the aldimine gives the final prod-
use of PBAIS instead of PhI(OAc) in the oxidation of al- uct nitrile. Iodobenzene was detected at the end of the re-
2
dehydes led to similar results, albeit after longer reaction action.
times. At the end of the reaction, the polymer species were
Table 2 Oxidation of Aldehydes to Nitriles with PhI(OAc) , SDS and Aqueous Ammonium Acetatea
2
Entry
Substrate
Product
PhI(OAc)2
Yield (%)b
PhI(OAc)2
Time (h)
2
Yield (%)b
Time (h)
9
0 (1st)
88 (2nd)
1 (3rd)
4
4
4
CHO
CN
1
2
3
4
93
95
93
95
9
CHO
CHO
CN
CN
4
4
4
93
91
94
7
7
7
Cl
Cl
Br
Br
CHO
CN
O2N
O2N
NO2
NO2
5
CHO
CN
92
4
93
7
CHO
CN
6
7
85
80
6
6
81
76
8
8
MeO
HO
MeO
HO
CHO
CN
CHO
CN
8
9
98
2
95
4
90
81
1
5
83
75
3
7
O
CHO
CHO
O
CN
CN
1
0
1
1
1
2
Me(CH ) CHO
Me(CH ) CN
83c
76c
8
8
78c
63c
12
12
2
6
2 6
n-C H CHO
n-C H CN
1
1
23
11 23
CHO
CN
13
79c
8
71c
12
a
b
c
Reaction conditions: aldehyde (1 mmol), aq NH OAc (3 mL, 30 mmol), PhI(OAc) (2 mmol), SDS (0.2 mmol), 70 °C.
Yields of isolated products unless otherwise noted.
Yields were determined by GC.
4
2
Synthesis 2010, No. 18, 3121–3125 © Thieme Stuttgart · New York

3
124
C. Zhu et al.
PAPER
NH4OAc
HOAc
OAc
OAc
Ph
I
O
NH3
H2O
OAc
Ph
R
C
H
N
I
R
C N
R
CH NH
–
– PhI
– HOAc
R
H
Scheme 2 A plausible reaction pathway
In conclusion, a simple and efficient method for the oxi- References
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(
ical Procedure
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(
6
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