Direct conversion of aromatic aldehydes into benzamides via oxidation with potassium permanganate in liquid ammonia

Article abstract of DOI:10.1055/s-0034-1378920

Oxidation of aromatic aldehydes by KMnO₄ in liquid ammonia gives amides directly. The reaction proceeds satisfactorily when the aldehydes are activated by electron-withdrawing substituents on the ring.

Full text of DOI:10.1055/s-0034-1378920

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Georg Thieme Verlag Stuttgart · New York
2015, 26, 84–86
84
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Synlett
D. Antoniak et al.
Letter
Direct Conversion of Aromatic Aldehydes into Benzamides via
Oxidation with Potassium Permanganate in Liquid Ammonia
Oxidation of Aldehydes to Amides
Damian Antoniak
KMnO4, NH3(l)
CHO
CONH2
Arkadiusz Sakowicz
Rafał Loska
(1.0 equiv)
R
R
–33 °C, 1 h
Mieczysław Mąkosza*
Institute of Organic Chemistry, Polish Academy of Sciences,
Kasprzaka 44/52, 01-224 Warsaw 42, Poland
icho-s@icho.edu.pl
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Received: 07.08.2014
Accepted after revision: 13.10.2014
Published online: 14.11.2014
of these salts exhibit high nucleophilic activity; thus it is
the solvent of choice for many reactions involving carban-
8
9
DOI: 10.1055/s-0034-1378920; Art ID: st-2014-d0658-l
ions and for industrial organic synthesis. Additionally, it is
inexpensive, easy to handle under anhydrous conditions,
and easy to remove and recover. Although ammonia can be
oxidized and its oxidation to nitric acid is a major industrial
process, liquid ammonia is resistant to common oxidants
Abstract Oxidation of aromatic aldehydes by KMnO in liquid ammo-
4
nia gives amides directly. The reaction proceeds satisfactorily when the
aldehydes are activated by electron-withdrawing substituents on the
ring.
and forms stable solutions of potassium permanganate
Key words aldehydes, amides, aminals, oxidation, liquid ammonia
10
even at room temperature under pressure. A KMnO solu-
4
tion in liquid ammonia has been efficiently applied to oxi-
dation of σH adducts of carbanions and other nucleophiles
to nitroarenes.11
The amide functionality is ubiquitous, and amides are
also versatile educts in organic synthesis; thus there is con-
tinuing interest in their synthesis. Of particular interest are
1
Ammonia is also a moderately active nucleophile capa-
H
possibilities of direct conversion of simple substrates into
amides which bypass conventional routes, such as reaction
of activated carboxylic acids with ammonia or partial hy-
drolysis of nitriles. In recent years there have been many re-
ports on direct conversion of aromatic aldehydes and ben-
zylic alcohols into amides via oxidative reactions in the
presence of an ammonia source. Thus treatment of aromat-
ic aldehydes with aqueous ammonia and iodine and hydro-
ble of forming σ adducts with highly electrophilic arenes,
particularly azines, and so a solution of KMnO4 in liquid
ammonia is an efficient agent for oxidative amination of
such arenes.10 We therefore predicted that treatment of an
aldehyde with such a solution should result in addition of
ammonia to the carbonyl group followed by oxidation of
the adduct to form an amide. Indeed, when solid KMnO4
was added to a solution of benzaldehyde in liquid ammonia
the characteristic color of the solution slowly turned dark
brown and, after evaporation of ammonia, the residue con-
tained benzamide. After experimentation a convenient pro-
cedure was found in which the aldehyde was dissolved in
2
gen peroxide gave amides in excellent yields. Other ways to
afford this transformation consist of conversion of alde-
hydes and primary alcohols into amides via reaction with
ammonium carbonate and tert-butyl hydroperoxide with
+
–
3
Et N I catalyst. Oxidative conversion of aldehydes and al-
liquid ammonia and, after stirring for one hour, KMnO (1.0
4
4
cohols into amides via reaction with oxygen and various
ammonia sources catalyzed by transition metals is de-
or 1.5 equiv) was added and the mixture stirred for another
hour. Excess permanganate was quenched with Na SO (3
equiv), the ammonia was evaporated, the residue treated
with 6 M hydrochloric acid, and the product extracted with
2
3
4
scribed in a few papers. New examples of oxidative amida-
5
tion of toluenes and styrenes and oxidative acylation with
6
aldehydes have been reported recently.
ethyl acetate or filtered, washed with aqueous NaHCO , and
3
Amongst a plethora of solvents used in organic synthe-
sis and industry, liquid ammonia is of great interest because
of its unique properties. Owing to its basicity and hydro-
gen-bond-accepting ability, liquid ammonia solvates effi-
the product recrystallized. The results of these experiments
are presented in Table 1.12
Aldehydes containing a halide or electron-withdrawing
substituents gave the corresponding amides in good yields
(Table 1, entries 2–8). The yields for nitrobenzaldehydes are
somewhat lower due to side reactions and partial decom-
position. Benzaldehyde and 1-naphthylcarboxyaldehyde
gave the corresponding amides in moderate yield, together
with small amounts of carboxylic acids. A careful analysis
of the mass balance for the reaction of 4-cyanobenzalde-
+
+
+
ciently inorganic cations such as Li , Na , K ; whereas, in
spite of its formal protic character, it does not efficiently
7
solvate anions. As a consequence it behaves as a dipolar
aprotic solvent, dissolving inorganic salts and sodium or
potassium salts of organic anions: alkoxides, enolates, and
7
carbanions. Moreover, in liquid ammonia solution, anions
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D. Antoniak et al.
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Table 1 Direct Oxidation of Aromatic Aldehydes to Amides
pathways of oxidation of σH adducts in oxidative nucleo-
philic substitution of hydrogen in arenes.14 On the other
hand, when the dimethyl acetal of 4-bromobenzaldehyde
was subjected to the reaction conditions, after acidic work-
up only 4-bromobenzaldehyde was obtained. This result
could be explained by much faster oxidation of the aminal
KMnO4, NH3(l)
CHO
CONH2
(1.0 equiv)
R
R
–33 °C, 1 h
Entry
Aldehyde (R)
Yield (%)
than the acetal function by KMnO , or by assuming that the
4
intermediate leading to an amide is an imine rather than an
aminal.
1
2
3
4
5
6
7
8
9
1
1
1
H
39
4-Cl
4-Br
3-Br
4-NC
75a
61
In conclusion, we have described a simple and practical
synthetic procedure by which aromatic aldehydes can be
directly converted into benzamides. The scope of the reac-
tion is somewhat limited by the concurrent formation of
carboxylic acids, but these side products can be readily re-
moved from the desired amides by simple washing with
aqueous base.
63
78b
4-O
2
2
N
N
50
56c
3-O
4-F
3
C
54
42c
24
21
0d
2,3-(CH=CH)
2
Supporting Information
0
1
2
2-F
3-F
Supporting information for this article is available online at
4-MeO
http://dx.doi.org/10.1055/s-0034-1378920.
S
u
p
p
o
nrtIo
i
g
f
rm oaitn
S
u
p
p
ortioIgnfmr oaitn
a
b
c
Yield of carboxylic acid: 15%.
Yield of carboxylic acid: 20%.
Conditions: 1.5 equiv KMnO
4
.
References and Notes
d
Yield of carboxylic acid: 85%.
(1) (a) Allen, C. L.; Wolliams, M. J. Chem. Soc. Rev. 2011, 40, 3405.
(b) Valeur, E.; Bradley, M. Chem. Soc. Rev. 2009, 38, 606.
hyde showed that, even in this case, side formation of the
carboxylic acid occurred. Its sodium salt was isolated in 20%
yield, together with a high yield of the expected 4-cyano-
benzamide (78%). Similarly, 4-chlorobenzaldehyde gave a
(c) Humpwey, J. M.; Chamberin, A. R. Chem. Rev. 1997, 97, 2243.
2) Shie, J.-J.; Fang, J.-M. J. Org. Chem. 2003, 68, 1158.
3) Wang, G.; Yu, Q.-Y.; Chen, S.-Y.; Yu, X.-Q. Org. Biomol. Chem.
(
(
2014, 12, 414.
(
4) Nie, R.; Shi, J.; Xia, S.; Shen, L.; Chen, P.; Hou, Z.; Xiao, F.-S.
J. Mater. Chem. 2014, 22, 18115; and references cited therein.
5) (a) Wang, Y.; Yamaguchi, K.; Mizuno, N. Angew. Chem. Int. Ed.
2012, 51, 7250. (b) Vanjari, R.; Guntreddi, T.; Nand Singh, K. Org.
Lett. 2013, 15, 4908. (c) Sharif, M.; Gong, J.-L.; Langer, P.; Beller,
M.; Wu, X.-F. Chem. Commun. 2014, 50, 4747.
75% yield of the amide and about 15% of the acid.
Aldehydes which are less prone to undergo nucleophilic
(
addition to the carbonyl group, such as anisaldehyde (Table
, entry 11), ortho-substituted aldehydes (2,3-dichloro-
1
benzaldehyde, 9-anthracenecarboxaldehyde), or aliphatic
aldehydes (n-octanal), form carboxylic acids exclusively. 2-
Fluorobenzaldehyde is a borderline case as it gave a nearly
equimolar mixture of 2-fluorobenzamide and 2-fluoroben-
zoic acid, together with some unreacted aldehyde.
(6) (a) Ekone-Kovi, K.; Wolf, C. Org. Synth. 2010, 87, 1. (b) Giguère-
Bisson, M.; Yoo, W.-J.; Li, C.-J. Org. Synth. 2011, 88, 14.
(c) Möhlmann, L.; Ludwig, S.; Blechert, S. Beilstein J. Org. Chem.
2013, 9, 602. (d) Wang, W.; Zhao, X.-M.; Wang, J.-L.; Geng, X.;
Gong, J.-F.; Hao, X.-Q.; Song, M.-P. Tetrahedron Lett. 2014, 55,
3192.
All benzamides obtained in the reactions summarized
in Table 1 are known compounds and their identity and pu-
(7) Reichardt, C. Solvents and Solvent Effects in Organic Chemistry;
Wiley-VCH: Weinheim, 2003, 3rd ed.
1
13
rity was confirmed by H NMR, C NMR, IR spectroscopy
and comparison of melting points with literature data.
Oxidation of aldehydes with aqueous solutions of
(8) Mąkosza, M. Tetrahedron 1968, 24, 175.
(9) (a) Ji, P.; Atherton, J.; Page, M. I. Org. Biomol. Chem. 2012, 10,
5732. (b) Ji, P.; Atherton, J.; Page, M. I. J. Org. Chem. 2011, 76,
KMnO at various pH values has been the subject of thor-
4
1425. (c) Ji, P.; Atherton, J.; Page, M. I. J. Org. Chem. 2011, 76,
3286.
13
ough mechanistic studies. However, the mechanistic con-
clusions from these studies cannot be extended to the oxi-
dation in liquid ammonia. It appears that conversion of al-
dehydes into amides in liquid ammonia proceeds via initial
addition of ammonia to the carbonyl group. This supposi-
tion is supported by the observed effects of substituents in
the aromatic rings on the reaction. Oxidation of the hypo-
thetical intermediates – aminals – could proceed via ab-
straction of hydride anions analogously to hypothetical
(10) (a) van der Plas, H. C.; Woźniak, M. Croat. Chem. Acta 1968, 59,
33. (b) Szpakiewicz, B.; Grzegorek, M. Russ. J. Org. Chem. 2004,
40, 829.
(
(
11) Mąkosza, M.; Staliński, K. Chem. Eur. J. 1997, 3, 2025.
12) General Procedure for the Oxidation of Aldehydes to Amides
in Liquid Ammonia
Under an argon atmosphere, liquid NH (25 mL) was condensed
3
in a two-neck round-bottom flask immersed in a dry ice cooling
bath and equipped with a dry ice reflux condenser. Aldehyde
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D. Antoniak et al.
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(
7.34 mmol) was added, and the resulting solution (or suspen-
3-Bromobenzamide
Colorless crystals; mp 152–156 °C (lit. 157–159 °C). IR (KBr):
6d
sion) was stirred for 1 h. KMnO (7.34 mmol, 1.16 g) was added,
4
the cooling bath was removed, and the reaction mixture was
stirred for another hour with gentle reflux of NH . Na SO (22.0
mmol, 2.78 g) was added, the reflux condenser was removed,
νmax = 3353, 3175, 1659, 1623, 1564, 1427, 1389, 1123, 1066,
–1 1
901, 794 cm . H NMR (400 MHz): δ = 7.44 (1 H, t, J = 7.8 Hz),
7.56 (1 H, br s), 7.73 (1 H, ddd, J = 7.8, 2.0, 1.0 Hz), 7.90 (1 H, dm,
3
2
3
13
and the NH was allowed to evaporate spontaneously. The dark-
J = 7.8 Hz), 8.08 (1 H, t, J = 1.8 Hz), 8.15 (1 H, br s). C NMR (100
MHz): δ = 122.5, 127.5, 131.1, 131.4, 134.9, 137.4, 167.3.
3
brown residue was treated with 6 M HCl (30 mL), and the
resulting precipitate was filtered, washed with H O (100 mL)
and sat. aq NaHCO3 (20 mL). All products were recrystallized
from EtOH.
(13) Wiberg, K. B.; Steward, R. J. Am. Chem. Soc. 1955, 77, 1786.
(14) Mąkosza, M.; Staliński, K. Tetrahedron Lett. 1998, 39, 3575.
2
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