Chromate oxidation of α-nitro alcohols to α-nitro ketones: Significant improvements to a classic method

Article abstract of DOI:10.3390/10121458

A series of eight alkyl and aryl α-nitro ketones were prepared by the potassium dichromate oxidation of the corresponding nitro alcohols. Short reaction times allowed for the easy isolation of pure nitro ketones that are devoid of starting materials and/o

Full text of DOI:10.3390/10121458

Molecules 2005, 10, 1458-1461
molecules
ISSN 1420-3049
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Chromate Oxidation of α-Nitro Alcohols to α-Nitro Ketones:
Significant Improvements to a Classic Method
Tarek Abou Elmaaty and Lyle W. Castle *
Department of Chemistry, Idaho State University, Campus Box 8023, Pocatello Idaho, 83209 USA.
Fax: +(1) 208-282-4373.
* Author to whom correspondence should be addressed. Email: castlyle@isu.edu
Received: 12 September 2005 / Accepted: 8 October 2005 / Published: 31 December 2005
Abstract: A series of eight alkyl and aryl α-nitro ketones were prepared by the
potassium dichromate oxidation of the corresponding nitro alcohols. Short reaction times
allowed for the easy isolation of pure nitro ketones that are devoid of starting materials
and/or other oxidation side products.
Keywords: Nitroalcohols, nitroketones, chromate oxidation.
Introduction
Our interest in α-nitro ketones stems from their usefulness in the synthesis of alkyl substituted
pyrazines [1]. A literature search revealed a limited number of procedures for their preparation. α-
Nitro ketones have been prepared in a one pot procedure by a solvent free nitroaldol (Henry reaction)
reaction followed by oxidation to the corresponding ketone using wet-alumina supported
chromium(VI) oxide [2], by the base catalyzed nitroaldol reaction using alumina supported potassium
fluoride, followed by oxidation using CrO3 along with the addition of montmorillonite K 10 [3], or by
the sodium dichromate oxidation of α-nitro alcohols [4] formed from the Henry reaction [5]. Other
general methods for the oxidation of primary and secondary alcohols have been reported and these
include the use of PCC [6] and the Swern [7] oxidation reactions. Finally α-nitro ketones can be
prepared through the reaction of acyl imidazoles with nitroalkanes in the presence of lithium hydride
in dimethyl sulfoxide [8].

Molecules 2005, 10
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Results and Discussion
This series of compounds reported here was prepared by a modified version of the sodium
dichromate oxidation [4]. In the method used by Hurd and Nilson [4] the sulfuric acid solution was
added to a mixture of the alcohols and sodium dichromate over a period of six hours, followed by long
mixing periods (2–72 hours), depending on the nitro ketone prepared. In our modification of the
procedure (given below), the nitro alcohol was gradually added to the potassium dichromate solution
followed by a ten-minute stirring period, then the drop-wise addition of the sulfuric acid solution over
a period of one hour. After the sulfuric acid addition is complete, the reaction is terminated by the
addition of water, followed by extraction and purification.
This method led to yields between 85-95%, with minimal purification, as compared to literature
yields of 68-86% [2], 76-90% [3] and 39-74% [4], which required more time and, in some cases,
complex methods. It should be noted that NMR spectral analysis of the crude material (prior to
Kugelrohr distillation) showed the compounds to be very pure, and thus they can be used directly in
most applications.
O2N
R1
O2N
R1
CrO3
O
R2
HO
R2
2a-h
1a-h
Entry #
2a
R1
R2
Yield % of 2*
CH3
C2H5
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
95
95
93
93
87
85
90
95
2b
2c
(CH2)2CH3
(CH2)3CH3
(CH2)5CH3
(CH2)6CH3
CH2CH(CH3)2
C6H5
2d
2e
2f
2g
2h
* Yield of 100% pure isolated product;
# Nitro alcohols a-g were prepared using the Henry reaction [9].
Conclusions
We have presented a facile route for the formation of α-nitroketones, useful intermediates in
heterocyclic synthesis.

Molecules 2005, 10
1460
Acknowledgements
The authors thank the National Science Foundation for providing the funds for the purchase of the
Varian Mercury 300 NMR (Award # 9980793) and the Fulbright Commission of Egypt to providing
living expenses for TAE.
Experimental
General
.
1
All H- and 13C-NMR spectra were recorded in CDCl3 on a Varian Mercury NMR spectrometer
operating at 300 and 100 MHz, respectively. Chemical shifts are expressed in ppm relative to TMS as
an internal standard. J values are given in hertz. Final products were purified by Kugelrohr distillation
using a Büchi B-580 Glass Oven. Starting materials were purchased from Aldrich and used without
further purification.
General Procedure for the Oxidation Reaction.
Potassium dichromate (0.069 mol) and water (35 mL) were mixed with constant mechanical
stirring in a 3-necked flask fitted with a condenser and an addition funnel. The corresponding nitro
alcohol 1a-h (0.13 mol) was gradually added to the cooled stirring solution and stirring was continued
for another 10 minutes. A cooled solution of H2SO4 (30 mL) and water (18 mL) was then added drop-
wise over a period of 1 hr., after which water (100 mL) was introduced into the reaction mixture. The
mixture was extracted with dichloromethane (3 x 150 mL), followed by subsequent washing with
water (200 mL) and 5% sodium carbonate (200 mL). The separated organic layer was dried over
anhydrous sodium sulfate, filtered and the solvent evaporated in vacuo. The liquid obtained was
distilled using a Kugelrohr apparatus to give the desired nitroketones 2a-2h.
3-Nitro-2-butanone (2a) [4]: 1H-NMR δΗ: 1.7 (d, 3H, CH3); 2.25 (s, 3H, CH3); 5.2-5.3 (q, 1H, CH).
1
3-Nitro-2-pentanone (2b) [4]: H-NMR δΗ: 1.05 (t, 3H, CH3); 2.0-2.2 (m, 2H, CH2, diastereotopic
protons); 2.3 (s, 3H, CH3); 5.1 (dd, 1H, CH; J=6, J=10); 13C-NMR δC: 193.5 (CO); 93.0 (CH), 26.5,
10.0 (2 CH3); 22.5 (CH2); COSY [10].
2-Nitro-3-hexanone (2c): 1H-NMR δΗ: 0.95 (t, 3H, CH3); 1.61 (m, 2H, CH2); 1.75 (d, 3H, CH3); 2.6 (t,
2H, CH2); 5.25 (q, 1H, CH); 13C-NMR δC: 200.0 (CO); 89.5 (CH); 41.0, 17.0 (CH2), 13.0 (CH3).
1
2-Nitro-3-heptanone (2d): H-NMR δΗ: 0.95 (t, 3H, CH3); 1.35(m, 2H, CH2); 1.6 (m, 2H, CH2); 1.75
(d, 3H, CH3); 2.6 (t, 2H, CH2); 5.25 (q, 1H, CH); 13C-NMR δC: 200.0 (CO); 89.5 (CH), 39.5, 26.0,
22.0 (CH2); 16.0, 14.0 (CH3).

Molecules 2005, 10
1461
2-Nitro-3-nonanone (2e): 1H NMR δΗ: 0.9 (t, 3H, CH3); 1.3 (m, 6H, 3CH2); 1.65 (m, 2H, CH2); 1.7 (d,
3H, CH3); 2.55 (t, 2H, CH2); 5.25 (q, 1H, CH); 13C-NMR δC: 200.0 (CO); 89.5 (CH); 39.5, 31.0, 29.5,
22.0(CH2); 15.0, 14.0 (CH3).
1
2-Nitro-3-decanone (2f): H-NMR δΗ: 0.8 (t, 3H, CH3); 1.3 (m, 6H, 3CH2); 1.52 (m, 2H, CH2); 1.65
(m, 2H, CH2); 1.7 (d, 3H, CH3); 2.6 (t, 2H, CH2); 5.25 (q, 1H, CH); 13C-NMR δC: 200.0 (CO); 89.5
(CH); 39.7, 31.9, 29.1, 29.0, 23.6, 22.8 (CH2); 15.2, 114.2 (2CH3).
1
5-Methyl-2-nitro-3-hexanone (2g): H-NMR δΗ: 0.8 (d, 6H, 2CH3), 1.55 (d, 3H, CH3), 2.06 (m, 1H,
CH), 2.41 (d, 2H, CH2), 5.05 (q, 1H, CH-NO2); 13C-NMR δC: 202.0 (CO), 95.3 (CH), 47.5 (CH2),
22.9 (CH), 22.0, 10.1(CH3).
1
2-Nitro-1-phenylpropanone (2h) [8]: H-NMR δΗ: 1.8 (d, 3H, CH3); 6.2 (q, 1H, CH); 7.4-8.0 (m, 5H,
arom-H); 13C-NMR δC: 190.0 (CO); 136.0, 134.0, 129.0, 128.0 (arom); 84.5 (CH), 16.5 (CH3).
References and Notes
1. Sato, N; Matsura, T. J. Chem. Soc. Perkin Trans. 1. 1996, 2345.
2. Ballini, R; Bosica, G; Parrini, M. Tetrahedron Lett. 1998, 39, 7963.
3. Mélot, J-M; Françoise, T-B; Foucaud, A. Tetrahedron Lett. 1986, 27, 493.
4. Hurd, C. D; Nilson, M. E. J. Org. Chem. 1955, 20, 927.
5. Seebach, D; Beck, A. K; Mukhopadhyay, T; Thomas, E. Helv. Chim. Acta 1982, 65, 1101.
6. Corey E. J; Suggs, J. W. Tetrahedron Lett. 1975, 16, 2647.
7. (a) Omura, K; Swern, D. Tetrahedron, 1978, 34, 1651; (b) Mancuso, A. J; Swern, D. Synthesis
1981, 3, 165.
8. Crumbie, R. L; Nimitz, J. S; Mosher, H. S. J. Org. Chem. 1982, 47, 4040.
9. (a) Henry and De Battice, Bull. Acad. Roy. Belg. 1898, 36, 149; [Chem. Zentr. 1898, II, 887]; (b)
Henry, Ber. 1899, 32, 865.
1
10. The H-NMR spectrum of 2b is interesting in that the resonance at 5.1 ppm appears as a doublet
of doublets. The connectivity of the –CH(NO2)CH2CH3 was verified by a COSY experiment: the
dd at δ 5.1 correlates with the m at δ 2.1, which correlates with the t at δ 1.05. A simple rigid
search of the rotation barrier about the C2-C3 bond using CAChe molecular modeling software
gave a rotational barrier of 82 kcal/mole. This indicates that the barrier to rotation is large and
explains the observed dd at 5.1 ppm for 2b.
Sample Availability: Available from the authors.
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