Potassium Phosphate Catalyzed Nitroaldol Reaction

Article abstract of DOI:10.1081/SCC-120027233

Potassium phosphate was found to catalyze condensation of nitroalkanes with various aliphatic and aromatic aldehydes to form nitroaldols in excellent yields in acetonitrile medium at room temperature.

Full text of DOI:10.1081/SCC-120027233

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Potassium Phosphate Catalyzed Nitroaldol Reaction
Uday V. Desai a , D. M. Pore a , R. B. Mane a , S. B. Solabannavar a & P. P. Wadgaonkar b
a Department of Chemistry, Shivaji University, Kolhapur, 416004, India
b Polymer Division, National Chemical Laboratory, Pune, India
Version of record first published: 16 Aug 2006.
To cite this article: Uday V. Desai, D. M. Pore, R. B. Mane, S. B. Solabannavar & P. P. Wadgaonkar (2004): Potassium
Phosphate Catalyzed Nitroaldol Reaction, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 34:1, 19-24
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 1, pp. 19–24, 2004
Potassium Phosphate Catalyzed
Nitroaldol Reaction
1
1
Uday V. Desai,1, D. M. Pore, R. B. Mane,
*
S. B. Solabannavar,1 and P. P. Wadgaonkar2
1Department of Chemistry, Shivaji University, Kolhapur, India
2Polymer Division, National Chemical Laboratory, Pune, India
ABSTRACT
Potassium phosphate was found to catalyze condensation of nitroalkanes
with various aliphatic and aromatic aldehydes to form nitroaldols in
excellent yields in acetonitrile medium at room temperature.
Key Words: Potassium phosphate; Catalysis; Nitroaldol; Nitroalkanol.
The reaction of a nitrostabilized carbanion with aldehydes and ketones
leading to the formation of nitroalkanols was discovered by Henry.[1] It is an
important C–C bond forming reaction and the resultant nitroalkanols are
useful intermediates in organic synthesis.[2] The b-nitroalkanols are used as
*
Correspondence: Uday V. Desai, Department of Chemistry, Shivaji University,
Kolhapur 416004, India; E-mail: uprabhu_desai@rediffmail.com.
19
DOI: 10.1081/SCC-120027233
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

20
Desai et al.
fungicides and are also useful in the synthesis of amino sugars and certain
antibiotics like ezomycines, tunicamycin as well as alkaloids.[3]
Henry reaction is routinely performed in an organic solvent in the
presence of a catalytic amount of base. Several basic catalysts like alkali and
alkaline earth metal hydroxides, carbonates, alkoxides, TBAF etc., are
normally used.[4,5] Various heterogeneous catalysts like alumina,[6] alumina
supported KF,[7] SiO2,[8] Amberlyst A-21,[9] Mg-Al hydrotalcite,[10] layered
zirconium phosphate,[11] benzyl trimethyl ammonium hydroxide,[12] and most
recently N,N-diethylpropylamine supported on amorphous silica (KG-60-
NEt2)[13] have also been used. The other procedures employing trialkylsilyl
chloride,[14] rhodium complex,[15] tetramethyl guanidine,[16] NaOH-cetyltri-
[18]
methyl ammonium chloride[17] and LiAlH4
somewhat laborious and need the use of nitroalkanes in excess.
are also reported which are
In the base catalyzed Henry reaction, aldol condensation and Cannizaro
reaction are the other competitive reactions, which need to be suppressed by
adopting proper experimental conditions. The control of basicity is also
essential to prevent the base catalyzed dehydration of the intermediate
nitroalkanols to nitroalkenes, which is a bit difficult when aromatic aldehydes
are used. Thus, to perform Henry reaction of aromatic aldehydes in the
presence of a base but not allowing the formation of nitroalkene is of interest.
Potassium phosphate is a mild base and has recently been used as an
effective catalyst in Knoevenagel condensation[19] and in the synthesis of
hexasubstituted cylcotriphosphazenes[20] as well as dithiocarbamates[21] while
the hydrated potassium phosphate is most recently used in the synthesis of
aromatic ketones.[22] In view of our interest in the synthesis of natural products
utilizing a nitroalkanol intermediate, we became interested in exploring the
usefulness of potassium phosphate to effect nitroaldol condensation and we
herein wish to report our findings obtained during the study.
As a case study, when a solution of m-nitrobenzaldehyde (1.51 g,
10 mmol) was stirred with nitroethane (0.83 g, 11 mmol) in the presence of
catalytic amount of potassium phosphate (0.1 g, 0.46 mmol) desired
nitroalkanol was obtained in almost quantitative yield (Sch. 1). To study the
effect of solvent on the rate as well as yield of reaction, reactions were also
Scheme 1.

Potassium Phosphate
21
carried out in ethanol, water, acetonitrile and tetrahydrofuran medium and the
results obtained (Table 1) clearly reveal that acetonitrile is the solvent of
choice. In order to prove generality of the method, various aliphatic as well as
aromatic aldehydes were condensed with nitroalkanes and the results obtained
are summarized in Table 2. As expected, the rate of the reaction was found to
be higher for aldehydes with electron withdrawing groups (entries 1 to 10)
than for those having electron donating groups (entries 11 to 14). Especially
with p-tolualdehyde and p-anisaldehyde (entries 11 to 14) the reaction did not
go to completion even after modifying the reaction conditions such as the use
of larger amount of catalyst, higher reaction temperature and higher
proportion of nitroalkanes.
In conclusion, potassium phosphate was found to be an efficient base
catalyst to effect nitroaldol reaction in excellent yields. The method affords a
diastereomeric mixture of nitroalkanols but the interesting feature of this
catalyst is that it does not bring about the dehydration of the resultant
nitroalkanols even when used in excess.
EXPERIMENTAL
General procedure: 1-(3-Nitrophenyl)-2-nitropropan-1-ol (2): To a stirred
solution of nitroethane (0.83 g, 11 mmol) in acetonitrile (15 mL) was added
anhydrous potassium phosphate (0.10 g, 0.46 mmol) followed by m-
nitrobenzaldehyde (1.51 g, 10 mmol) and stirring continued. On completion
of reaction (TLC monitoring) water (30 mL) was added to it and the reaction
mixture was extracted with diethyl ether (50 mL). The ether extract was
washed with water (3 ꢀ 20 mL) and dried over anhydrous Na2SO4. Removal
of the solvent gave a residue which was filtered through a short column of
silica gel to afford 1-(3-nitrophenyl)-2-nitropropan-1-ol (2) (2.2 g, 93%) m.p.
748C (Lit.10 748C). IR (Nujol): 3510, 1520, 1352, 1210, 1050, 900, 816,
1
740 cm21. H NMR (200 MHz, CDCl3): d 1.4 (d, J ¼ 7.3 Hz, 3H), 1.5 (d,
J ¼ 5.8 Hz, 3H), 3.4 (d, J ¼ 10.8 Hz, 1H), 4.7–4.85 (m, 1H), 5.2 (dd,
J ¼ 5.4 Hz each, 1H), 7.55–7.8 (m, 2H), 8.2 (m, 2H); 13CNMR (50.3 MHz,
CDCl3): d 11.4, 15.8, 72.5, 86.5, 87.6, 120.8, 121.6, 123, 123.6, 129.5, 132,
133, 140, 147.9.
Table 1. Condensation of m-nitrobenzaldehyde with nitromethane.
Solvent
CH3CN
THF
EtOH
H2O
Time (min)
Yield (%)
15
95
30
93
180
60
180
30

22
Desai et al.
Table 2. Potassium phosphate catalyzed preparation of nitroaldols.
Entry
R
R0
Time (min)
Yield (%)a,,b
1
2
m-Nitrophenyl
m-Nitrophenyl
o-Nitrophenyl
o-Nitrophenyl
p-Chlorophenyl
p-Chlorophenyl
m-Chlorophenyl
m-Chlorophenyl
o-Chlorophenyl
o-Chlorophenyl
p-Methylphenyl
p-Methylphenyl
p-Methoxyphenyl
p-Methoxyphenyl
Isopropyl
CH3
C2H5
CH3
15
20
95
93
95
92
93
89
91
89
95
90
45
40
20
10
86
84
88
81
89
87
3
20
25
4
C2H5
CH3
5
35
45
6
C2H5
CH3
7
45
55
8
C2H5
CH3
9
50
55
10
11
12
13
14
15
16
17
18
19
20
C2H5
CH3
180
180
72c
72c
130
135
135
135
120
130
C2H5
CH3
C2H5
CH3
Isopropyl
Ethyl
C2H5
CH3
Ethyl
n-Propyl
n-Propyl
C2H5
CH3
C2H5
aAll the compounds showed satisfactory spectroscopic data.
bYields refer to pure isolated products.
cTime in hours.
The spectral data of all the other compounds synthesized were in
agreement with those reported.[10]
ACKNOWLEDGMENT
One of the authors (UVD) thanks UGC, New Delhi, for financial
assistance.
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Potassium Phosphate
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Received in the USA July 15, 2003