Benzyltrimethylammonium hydroxide catalysed nitroaldol condensation

Article abstract of DOI:10.1081/SCC-100107010

Benzyltrimethylammonium hydroxide is found to be a very efficient catalyst for nitroaldol condensation in a short time with excellent yield.

Full text of DOI:10.1081/SCC-100107010

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BENZYLTRIMETHYLAMMONIUM HYDROXIDE CATALYSED
NITROALDOL CONDENSATION
Vivek J. Bulbule a , G. K. Jnaneshwara a , Ravindra R. Deshmukh a , Hanumant B. Borate
a & Vishnu H. Deshpande b
a Division of Organic Chemistry, Technology, National Chemical Laboratory, Pune, 411
008, India
b Division of Organic Chemistry, Technology, National Chemical Laboratory, Pune, 411
008, India
Published online: 16 Aug 2006.
To cite this article: Vivek J. Bulbule , G. K. Jnaneshwara , Ravindra R. Deshmukh , Hanumant B. Borate & Vishnu
H. Deshpande (2001): BENZYLTRIMETHYLAMMONIUM HYDROXIDE CATALYSED NITROALDOL CONDENSATION, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:23, 3623-3626
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SYNTHETIC COMMUNICATIONS, 31(23), 3623–3626 (2001)
BENZYLTRIMETHYLAMMONIUM
HYDROXIDE CATALYSED
NITROALDOL CONDENSATION
Vivek J. Bulbule, G. K. Jnaneshwara,
Ravindra R. Deshmukh, Hanumant B. Borate,
and Vishnu H. Deshpande*
Division of Organic Chemistry, Technology,
National Chemical Laboratory,
Pune – 411 008, India
ABSTRACT
Benzyltrimethylammonium hydroxide is found to be a very
efficient catalyst for nitroaldol condensation in a short time
with excellent yield.
The nitroaldol condensation is a key reaction in the synthesis of
several biologically active compounds.1 The nitro group of nitroaldol prod-
ucts can be easily functionalised to amine,2 can be converted into carbonyl
compounds,3 and easily denitrated by further functional group manipula-
tions.4 Several catalysts have been reported in literature to effect the Henry
reaction e.g. alumina,5 amberlyst A-21,6(a) Mg–Al–Hydrotalcite,6(b) KF on
alumina,7 NaOH with the surfactant catalyst hexadecyltrimethylammonium
*Corresponding author. Fax: þ91 020 5893614.
3623
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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3624
BULBULE ET AL.
chloride8 etc. Recently TBAF hydrate9 has been used, but the use of 1 to 2
equivalents suppresses its use in synthetic organic chemistry. The classical
nitroaldol reaction, performed by using strong bases, often results in the
formation of side products by the aldol condensation and Cannizzaro
Scheme 1.
Table 1. Benzyltrimethylammonium Hydroxide Catalyzed Preparation of
Nitroalkanolsa
Entry
1
R
Nitroalkane
Time (min)
Yieldb(%)
p-Chlorophenyl
Nitroethanec
Nitroethaned
Nitroethaned
Nitroethanec
Nitroethaned
Nitroethanec
Nitroethaned
Nitroethaned
Nitroethaned
Nitroethanec
Nitroethaned
Nitroethanec
Nitroethaned
Nitroethanec
Nitroethaned
Nitroethaned
Nitroethanec
Nitroethaned
10
6
4
12
894
88
6
10
4
91
95
98
90
2
3
p-Nitrophenyl
p-Methoxyphenyl
4
2-Furyl
1
8
5
8
5
6
7
o-Chlorophenyl
m-Nitrophenyl
Phenyl
94
98
83
8
91
86
82
10
6
8
9
o-Hydroxyphenyl
15
12
10
893
6
878
5
892
5
3,4,5-Trimethoxyphenyl
10
11
2-Chloro-3-quinolinyl
Isobutyl
8
8
0
0
12
13
m-Nitrophenyl
m-Nitrophenyl
Nitromethanec
Nitromethaned
Nitropropane
98
98
6
aAll the nitroalkanols showed satisfactory spectroscopic data. bIsolated yield after
c
column chromatographic purification. 1.1 equivalent of nitroalkane. dNitroalkane
used in excess.

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NITROALDOL CONDENSATION
3625
6(b)
reaction of aldehydes or olefin formation. In our continuing interest
to
explore the utility of various catalysts to effect the Henry reaction we have
developed a convenient and quick method for the effective synthesis of
nitroaldols using benzyltrimethylammonium hydroxide as a catalyst to
give excellent yields of nitroaldols (Scheme 1) and we wish to report our
results herein.
When aldehydes were stirred with 1.1 equivalent of nitroalkanes in
water containing a few drops of THF,10 in presence of catalytic amount
of benzyltrimethylammonium hydroxide at room temperature the desired
nitroaldol products were formed in excellent yields. The substrates contain-
ing electron withdrawing groups were found to undergo faster reaction
(Entries 2, 6, 12 and 13) compared to electron rich substituted aromatic
compounds and give almost quantitative yield. An aliphatic aldehyde also
underwent nitroaldol condensation (Entry 11). Efforts were made to achieve
quantitative yields by modifying reaction parameters. It was observed that
instead of using a mixture of water and THF as solvent, when reactions were
run using an excess of nitroalkane, various aldehydes underwent nitroaldol
reactions in almost quantitative yields and in a short period of 4–15 min
(Table 1).
In conclusion, we have demonstrated that benzyltrimethylammonium
hydroxide can be used as an effective catalyst to prepare various nitroalk-
anols in excellent yields by nitroaldol condensation.
ACKNOWLEDGMENTS
VJB thanks LTMT Mumbai, JGK and RRD thank CSIR, New Delhi,
for the award of senior research fellowship.
REFERENCES
1. (a) Koshinen, P.M.; Koshinen, A.M.P. Synthesis 1998, 1975; (b) Rosini,
G.; Ballini, R. Synthesis 1988, 833; (c) Tsay, S.C.; Patel, V.H.; Hwu,
J.R. Synlett 1998, 939; (d) Ballini, R.; Bosica, G. Eur. J. O. Chem. 1998,
2, 355; (e) Scarpi, D.; Occhiato, E.G.; Guorna, A. J. Org. Chem. 1999,
64, 1727.
2. Barett, A.G.M.; Spilling, D.C. Tetrahedron Lett. 1988, 29, 5733.
3. (a) Ceccherelli, P.; Curini, M.; Marcotullio, M.C.; Epifano, F.; Rosati,
O. Synthetic Comm. 1998, 28, 3057; (b) Adam, W.; Makosza, M.C.;
Moller C.R.; Zhao, C.G. Synlett 1998, 1335; (c) Ballini, R.; Papa, F.;
Abate, C. Eur. J. O. Chem. 1999, 1, 8 7.

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BULBULE ET AL.
4. (a) Ono, N.; Kaji, A. Synthesis 1986, 693; (b) Ballini, R.; Curini, M.;
Epifano, F.; Marcotullio, M.C.; Rosati, O. Synlett 1998, 1049 and
references cited therein; (c) Rosini, G.; Ballini, R. Synthesis 1988, 833.
5. Rosini, G.; Ballini, R.; Sorrenti, P. Synthesis 1983, 1014.
6. (a) Ballini, R.; Petrini, M.; Rosini, G. Synthesis 1987, 711; (b) Bulbule,
V.J.; Deshpande, V.H.; Velu, S.; Sudalai, A.; Sivasanker, S.; Sathe,
V.T. Tetrahedron 1999, 55, 9325.
7. Melot, J.M.; Texier-Boullet, F.; Foucraud, A. Tetrahedron Lett. 1986,
7, 493.
8. Ballini, R.; Bosica, G. J. Org. Chem. 1997, 62, 425.
9. Hanessian, S.; Devasthale, P. Tetrahedron Lett. 1996, 37, 987.
10. Experimental procedure: To a mixture of 3-nitrobenzaldehyde (500 mg,
3.31 mmole) and nitroethane (272 mg, 3.63 mmole) in water (5 ml) and
THF (0.4 ml) was added 1 drop of benzyltrimethylammonium hydro-
xide (40% aq. solution) at room temperature. The mixture was stirred
at room temperature for 4 min. After the reaction was complete (TLC),
excess water was added and the aqueous layer was extracted with
chloroform (2 ꢀ 20 ml). The combined organic layer was dried over
Na2SO4 and concentrated. The residue was purified by flash chroma-
tography to afford 1-(3-nitrophenyl)-2-nitropropan-1-ol (734 mg,
1
98%); H NMR (200 MHz, CDCl3): d 1.40 (d, J ¼ 7.3 Hz, 3H), 3.46
(d, J ¼ 4 Hz, 1H, D2O exchangeable), 4.70–4.85 (m, 1H), 5.22 (dd,
J ¼ 7.5 Hz, 4 Hz, 1H), 7.60 (t, J ¼ 8.1 Hz, 1H), 7.70–7.80 (m, 1H),
8.15–8.30 (m, 2H); MS (m/z rel. intensity %) 226 Mþ (5), 179 (45),
151 (76), 150 (95), 149 (100), 135 (8), 121 (5), 115 (10), 105 (50), 90 (9)
and 77 (52).
Received in the UK October 30, 2000

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