Oxidative deamination of amines using sodium nitrite

Article abstract of DOI:10.1080/00397911.2011.624663

A novel synthetic utility of sodium nitrite for oxidative deamination is described. Aromatic and aliphatic amines compounds were successfully converted into the corresponding carbonyl compounds in the presence of sodium nitrite, potassium iodide, and molecular oxygen under reflux conditions. The method is applicable for both primary and secondary amines for moderate to good yields of corresponding carbonyl compounds. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.

Full text of DOI:10.1080/00397911.2011.624663

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Oxidative Deamination of Amines Using
Sodium Nitrite
a
a
Hemchandra K. Chaudhari & Vikas N. Telvekar
a
Department of Pharmaceutical Sciences and Technology, Institute
of Chemical Technology, Matunga, Mumbai, India
Accepted author version posted online: 17 May 2012.Version of
record first published: 21 Feb 2013.
To cite this article: Hemchandra K. Chaudhari & Vikas N. Telvekar (2013): Oxidative Deamination
of Amines Using Sodium Nitrite, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 43:8, 1155-1160
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Synthetic Communications , 43: 1155–1160, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.624663
OXIDATIVE DEAMINATION OF AMINES USING
SODIUM NITRITE
Hemchandra K. Chaudhari and Vikas N. Telvekar
Department of Pharmaceutical Sciences and Technology, Institute of
Chemical Technology, Matunga, Mumbai, India
GRAPHICAL ABSTRACT
Abstract A novel synthetic utility of sodium nitrite for oxidative deamination is described.
Aromatic and aliphatic amines compounds were successfully converted into the correspond-
ing carbonyl compounds in the presence of sodium nitrite, potassium iodide, and molecular
oxygen under reflux conditions. The method is applicable for both primary and secondary
amines for moderate to good yields of corresponding carbonyl compounds.
Supplemental materials are available for this article. Go to the publisher’s online edition
1
of Synthetic Communications to view the free supplemental file.
Keywords Aldehyde; amines; ketone; oxidation; sodium nitrite
INTRODUCTION
The oxidation of amines to generate a significant class of available building
blocks and fundamental synthetic intermediates has received much attention from
organic chemists. Oxidation of amines can lead to functional groups including
[
1–4]
imines, amides, nitro, oximes, nitriles, aldehydes, and ketones.
of amines to carbonyl compounds has been reported with various metal oxidizing
The conversion
[
5–8]
reagents such as KMnO , K FeO , Pb(OAc) , NiO , and HgO-I .
A literature
survey also indicates that Pd=C under microwave irradiation and RuO under press-
4
2
4
4
2
2
[
ure can be used for this transformation at higher temperatures. Very recently,
9]
[
10]
ZnCr O trihydrate was used for oxidative deamination at room temperature.
7
2
There are several two-step processes available for conversion of amines to carbonyl
compounds. However, these methods suffer from disadvantages such as the require-
ment for larger amount of reagents and poor yield of the products.
In our previous study of bromodecarboxylation using NaNO and 48% HBr at
2
[11]
room temperature, we observed that NaNO in combination with other reagents
2
Received July 29, 2011.
Address correspondence to Vikas N. Telvekar, Department of Pharmaceutical Sciences and
Technology, Matunga, Mumbai, India. E-mail: vikastelvekar@rediffmail.com
1
155

1156
H. K. CHAUDHARI AND V. N. TELVEKAR
2
Scheme 1. Formation of benzaldehyde using NaNO and KI.
Table 1. Different halogen reagents for conversion of benzylamine to benzaldehyde
No.
Salt
Time (h)
Yield (%)
1
2
3
4
5
6
Tetraethylammonium bromide
Tetrabutylammonium iodide
4
4
4
4
4
3
NR
NR
5
KBr
NaBr
NaI
KI
5
20
90
can be used for the preparation of carbonyl compound from the corresponding
amine at different reaction conditions.
Initially we selected benzylamine as a model substrate (Scheme 1). Exposure of
sodium nitrite to benzylamine in the presence of potassium iodide in an acetonitrile=
water mixture in the presence of oxygen at reflux temperature resulted in the forma-
tion of benzaldehyde. In the absence of oxygen, no reaction was observed.
Further screening for the reaction conditions revealed that 1 equivalent of
sodium nitrite and 2 equivalents of KI are required to furnish benzylamine to benzal-
dehyde in 90% yield. The reaction does not take place in dry organic solvents
(CH Cl , CHCl , CH CN), but 50% aqueous organic solvents (water–organic sol-
2 2 3 3
vent, 1:1) gave benzaldehyde without affecting yield and reaction time. The reaction
was also carried out at room temperature but a slower reaction rate was observed.
To check the possibility of substitution of KI with other halogen reagents, the
reactions were carried out using KBr, NaI, NaBr, tetraethyl ammonium bromide,
and tetrabutyl ammonium iodide instead of KI (Table 1).
Table 1 clearly indicates the iodine salts are suitable for this conversion, whereas
as compared to KI lower yield was observed in the case of NaI. Almost negligible
yields were observed when KI was replaced by bromide salts. No reactions were
observed in the cases of tetraethylammonium bromide and tetrabutylammonium
iodide.
RESULTS AND DISCUSSION
To evaluate the scope of this new method, these reaction conditions were
applied to a variety of aromatic and aliphatic amines and converted into correspond-
ing carbonyl compounds. Results are presented in Table 2. Primary and secondary
aromatic amines were successfully converted into the corresponding aldehydes and
ketones (Table 2, entries 1–7). The lower reaction rate was observed in the case of
aliphatic primary and secondary amines (Table 2, entries 10 and 11). The method
is also useful for the cyclic compounds; cyclohexamine and cyclopentamine were suc-
cessfully converted into corresponding cyclohexanone and cyclopentanone (Table 2,

OXIDATIVE DEAMINATION OF AMINES
1157
a
2
Table 2. Oxidative deamination of amines in the presence of NaNO and KI
b
Yield (%)
Entry
1
Substrate
Product
Time (h)
3
90
2
3
4
3
3
3
90
92
90
5
8
80
6
7
8
8
85
85
8
9
8
8
75
75
1
1
0
1
9
65
65
12
12
12
70
a
2
Reaction conditions: substrate (10 mmol), NaNO (10 mmol), KI (20 mmol) in 20 mL acetonitrile–
water (1:1), reflux temperature.
b
Isolated yields after column chromatography and structures were confirmed by comparison of IR and
H NMR with authentic materials.
1

1158
H. K. CHAUDHARI AND V. N. TELVEKAR
entries 8 and 9). Under these reaction conditions, ester and methoxy groups are
stable (Table 2, entries 3 and 4). Both electron-withdrawing and electron-donating
substitutes are suitable for this transformation (Table 2, entries 2, 3, 4, 6, and 7).
In conclusion, we have exploited a novel application of NaNO in combination
2
with KI for oxidative deaminations of primary and secondary amines for prep-
aration of corresponding carbonyl compounds in moderate to good yields. The
described method has simple workup and is used for both substituted primary and
secondary aliphatic amines.
Representative Procedure for Oxidative Deamination of
Benzylamine (Table 1, Entry 1)
In a mixture of 50% acetonitrile=water (20 mL), benzylamine (1.07 g, 10 mmol)
and KI (3.30 g, 20 mmol) were stirred at room temperature. Aqueous solution (5 mL)
of NaNO (0.69 gm, 10 mmol) was added dropwise to that stirred solution. The reac-
2
tion mixture was subjected to reflux. During the reaction, oxygen was bubbled in the
reaction mixture. After completion of the reaction [as monitored by thin-layer chro-
matography (TLC)], ethyl acetate (20 mL) was added to the reaction mixture and
stirring was continued for 2 min. The organic layer was separated; washed with dilute
HCl (2 ꢀ 20 mL), 10% aqueous NaHCO (2 ꢀ 20 mL) solution, followed by water
3
(
3 ꢀ 20 mL); dried over Na SO ; and concentrated in vacuum. The remaining residue
2
4
was purified by column chromatography on silica gel (hexane = ethyl acetate ¼ 9=1)
to yield benzaldehyde (0.954 g, 90%) as a colorless oil.
Benzaldehyde (Table 2, Entry 1)
ꢁ
ꢂ1 1
Bp: 178 C; IR (neat): 1694 cm ; H NMR (CHCl , 60 MHz): d 7.50–7.60 (3H,
m), 7.85–7.90 (2H, m), 10.03 (1H, s). Mp, IR, and NMR values match with literature
values.
3
[
12a]
4-Nitrobenzaldehyde (Table 2, Entry 2)
ꢁ
ꢂ1
1
; H NMR (CHCl3,
Pale yellow solid; mp: 104 C; IR (KBr): 1676 cm
6
IR, and NMR values match with literature values.
0 MHz): d 8.0 (2H, d, J ¼ 8.3 Hz), 8.50 (2H, d, J ¼ 8.6 Hz), 10.10 (1H, s). Mp,
[
12a]
4-Methoxylbenzaldehyde (Table 2, Entry 4)
ꢁ
ꢂ1
1
Colorless liquid; bp: 247 C; IR (neat): 1682 cm ; H NMR (CHCl , 60 MHz):
3
d 3.90 (3H, s), 7.0 (2H, d, J ¼ 8.6 Hz), 7.80 (2H, d, J ¼ 8.4 Hz), 9.80 (1H, s). Mp, IR,
[
12a]
and NMR values match with literature values.
Acetophenone (Table 2, Entry 5)
ꢁ
ꢂ1
1
Colorless liquid; bp: 201 C; IR (film): 1682 cm ; H NMR (CDCl , 60 MHz)
3
d 7.7–7.9 (m, 2H), 7.0–7.5 (m, 3H), 2.5 (s, 3H). Bp, IR, and NMR values match with
literature values.
[12b]

OXIDATIVE DEAMINATION OF AMINES
1159
Cyclohexanone (Table 2, Entry 8)
ꢁ
ꢂ1
1
Colorless liquid; bp: 155 C; IR (neat): 1717 cm ; H NMR (CDCl , 60 MHz)
3
d 2.2–2.4 (m, 4H), 1.7–1.9 (m, 6H). Bp, IR, and NMR values match with literature
values.
[
12b]
Pentanal (Table 2, Entry 10)
ꢁ
ꢂ1
1
Colorless liquid; bp: 102 C; IR (neat): 1725 cm ; H NMR (CDCl , 60 MHz)
3
d 9.4 (s, 1H), 2.2 (m, 2H), 1.5 (m, 4H), 0.8 (m, 3H). Bp, IR, and NMR values are
matches with literature values.
[12c]
Hexan-2-one (Table 2, Entry 11)
ꢁ
1
Yellow liquid; bp: 127 C; H NMR (CDCl , 60 MHz) d 1.5 (m, 4H), 2.4
3
[
12d]
(
m, 5H), 0.9 (m, 3H). Bp and NMR values match with literature values.
Glutaraldehyde (Table 2, Entry 12)
ꢁ
ꢂ1
1
Colorless liquid; bp: 188 C; IR (neat): 1715 cm ; H NMR (CDCl , 60 MHz)
3
d 9.5 (t, 2H), 2.6 (m, 4H), 1.2 (m, 2H). Bp, IR, and NMR values match with litera-
ture values.
[
12e]
ACKNOWLEDGMENT
V. N. T. and H. K. C. thank the University Grants Commission for financial
support under the UGC-SAP program.
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