Communication
pubs.acs.org/OPRD
A Convenient and “Greener” Synthesis of Methyl Nitroacetate
Eric C. Johnson,† Pablo E. Guzmán,*,† Leah A. Wingard,† Jesse J. Sabatini,*,†
and Rose A. Pesce-Rodriguez‡
†
Energetics Technology Branch, ‡Energetic Materials Science Branch, U.S. Army Research Laboratory, Aberdeen Proving Ground,
Maryland 21005, United States
*
S Supporting Information
ABSTRACT: A new procedure for the synthesis and
isolation of methyl nitroacetate is described. The
previously published method required drying the explosive
dipotassium salt of nitroacetic acid in a vacuum desiccator,
followed by grinding this material into a fine powder with a
mortar and pestle prior to esterification. To obtain the
desired product, benzene was employed as the extraction
solvent, sodium sulfate was used as the drying agent, and
two distillations were required. The new procedure
eliminates drying and grinding of the explosive dipotas-
sium salt, employs ethyl acetate or dichloromethane as the
extraction solvent, eliminates the need for a drying agent,
and requires a single distillation to furnish the end product
in high yield and purity.
■
INTRODUCTION
The presence of the unbranched nitroacetic ester moiety in
organic synthesis has found wide application, as evidenced by
the historical review written by Shipchandler.1 More recently,
nitroacetic esters have been used in palladium-catalyzed cross-
coupling reactions with aryl halides to generate 2-aryl-2-
nitroacetates.2 Most recently, Machetti and co-workers have
found that nitroacetic esters react with alkenes and alkynes in
the presence of DABCOand in the notable absence of a
dehydrating agentto produce isoxazolines and isoxazoles.3
One such nitroacetic ester that can be used for the
aforementioned applications is the commercially available
methyl nitroacetate. Though a relatively expensive material to
buy,4 methyl nitroacetate can be prepared in a two-step process
from inexpensive materials, as summarized in Scheme 1.5 The
Scheme 1. Original Synthesis of Methyl Nitroacetate
treatment of nitromethane with potassium hydroxide at a high
temperature results in the formation of the dipotassium
nitronate salt (1, see Figure S1 in the Supporting Information
for the proposed mechanism). The conversion of 1 to methyl
nitroacetate (2) is realized upon exposure of 1 to sulfuric acid
in methanol at low temperature.6
This article not subject to U.S. Copyright.
Published 2017 by the American Chemical
Society
■ RESULTS AND DISCUSSION
Although the synthesis of methyl nitroacetate appears trivial,
the current route suffers from several issues. When 1 is
synthesized, reports call for the material to be dried in a vacuum
desiccator overnight and then ground into a fine powder with a
mortar and pestle (Figure 1). However, 1 is a potentially shock
sensitive and explosive material, as has been pointed out by an
explosion of the dry powder.7 Thus, keeping 1 wet and using it
in the next step without isolation would provide a significant
increase in safety protocols when handling the material.
Second, when purifying 2, benzene is used as the solvent of
choice for extraction. Benzene, however, is a toxic solvent and
has negative health effects.8 Third, two distillations are required
to obtain 2 in high purity. One distillation is needed to remove
benzene, and a second distillation under reduced pressure is
needed to isolate the pure product. Thus, despite appearing to
be a simple synthesis, synthesizing methyl nitroacetate has
historically been a labor-intensive process plagued by safety and
toxicity issues. In light of these issues, an alternative process was
investigated to make the synthesis of methyl nitroacetate in a
more safety conscious, environmentally responsible, and timely
manner.
While the general synthesis in Scheme 1 did not change, the
process of isolating pure methyl nitroacetate was altered
significantly to afford 2 in a safer and “greener” process. The
new process is displayed in Figure 2. In this process, 1 was
isolated by filtration and washed with methanol per the original
procedure. The material was not dried on the filter, however,
and was transferred wet to a round-bottom flask, where it was
used immediately in the esterification step.
Once the esterification reaction was complete, the reaction
mixture was filtered, the solid was discarded, and the mother
liquor was concentrated by rotary evaporation as per the
original procedure. Instead of adding benzene, water was added
to the resulting oil, and the crude material was neutralized with
a saturated aqueous solution of NaHCO3. Failure to neutralize
the crude esterification product prior to distillation resulted in
an unstable protonated species, which under elevated temper-
ature, can result in a detonation.
After neutralization, 2 was isolated by a simple extraction
with ethyl acetate or dichloromethane.9 Following rotary
evaporation of the solvent, vacuum distillation of the dark
amber liquid afforded 2 in high purity as a clear, colorless liquid.
The overall yield for the new procedure was 38%. Although this
Received: March 12, 2017
Published: June 15, 2017
1088 DOI: 10.1021/acs.oprd.7b00093
Org. Process Res. Dev. 2017, 21, 1088−1090
Organic Process Research & Development
Figure 1. Original synthesis process of methyl nitroacetate.
Figure 2. New synthesis process of methyl nitroacetate.
yield is lower than the ca. 52% overall yield reported
previously,5 the new environmentally conscious and improved
safety process makes the sacrifice in yield acceptable. DSC
analysis showed that 2 had a reasonable thermal stability, with a
thermal onset temperature of 251 °C, and a peak exothermic
decomposition temperature of 272 °C.
■ CONCLUSION
In summary, a synthesis for methyl nitroacetate has been
developed, with an emphasis on minimizing explosion hazards,
improving the “green” aspects of the synthesis, and improving
the general process in an effort to make the material in a more
efficient manner. Given the many potential synthetic uses of
methyl nitroacetate, this new procedure can be used to provide
this organic building block in a safer manner.
■ EXPERIMENTAL SECTION
Chemicals and solvents were used as received from Sigma-
Aldrich. 1H and 13C NMR spectra were recorded using a
Bruker 400 and 100 MHz instrument, respectively. The
chemical shifts quoted in ppm in the text refer to typical
standard tetramethylsilane (1H, 13C) in CDCl3 as the solvent.
Infrared spectra were measured with a Bruker Alpha-P FTIR
instrument. Decomposition temperatures were measured at a
heating rate of 5 °C/min using a TA Instruments Q10 DSC
instrument.
Methyl Nitroacetate (2). Warning: Although no incidents
occurred, the intermediates generated, as well as the end product,
are energetic and should be handled as if they are explosive
materials. It is essential that all reactions be conducted behind a
1089
Communication
blast shield and that proper protective equipment, including a face
shield, be worn at all times during the operation.
To a three-necked 3 L round-bottom flask, equipped with a
mechanical stirrer, was added H2O (112 mL) and KOH (224 g,
4.00 mol, 4.00 equiv). Nitromethane (54 mL, 1.00 mol, 1.00
equiv) was added over 0.5 h. During the addition, the internal
temperature of the reaction reached 70 °C. After 5 min, a
yellow tinge was visible, and then the reaction turned reddish-
brown. Once the addition was complete, the mechanical stirring
was stopped, and the reaction was heated for 1 h (oil bath
temperature = 160 °C, internal temperature = 135 °C). The
reaction was then allowed to cool to room temperature, and the
crude salt was collected by Büchner filtration. The salt was
rinsed with MeOH until the salt was colorless. The salt, still
wetted with MeOH in the Büchner funnel, was immediately
transferred to a three-necked 3 L round-bottom flask, and
MeOH (465 mL) was added with overhead stirring. The
suspension was cooled to −15 °C. Once cooled, concentrated
H2SO4 (116 g, 1.16 mol) was added dropwise with vigorous
stirring, over 1 h via a pressure-equalizing dropping funnel. The
reaction was maintained at −15 °C for the duration of the
addition. The reaction was then allowed to stir and was
gradually warmed to room temperature overnight. The
resulting precipitate was removed by filtration with a glass
frit, and the filtrate was concentrated under reduced pressure to
remove as much MeOH as possible. The material was then
transferred to an Erlenmeyer flask, 200 mL of H2O was added,
and a saturated aqueous solution of NaHCO3 was carefully
added, with stirring, until neutrality was achieved. The solution
was transferred to a separatory funnel and was extracted with
DOI: 10.1021/acs.oprd.7b00093
Org. Process Res. Dev. 2017, 21, 1088−1090
Organic Process Research & Development Communication

ethyl acetate or dichloromethane (4 × 250 mL). The combined

organic extracts were washed with brine and water. The
material was concentrated under reduced pressure to yield an
amber colored liquid. Distillation under reduced pressure
yielded 22.67 g (38%) of the desired product as a clear colorless
liquid, bp 65 °C (3.9 Torr). 1H NMR (400 MHz; CDCl3) δ
5.18 (s, 2H), 3.87 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
162.5, 76.2, 53.6; IR (neat): 3041, 2967, 1751, 1557; Tdec = 251
°C (onset), 272 °C (peak).

■
*
ASSOCIATED CONTENT
S Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.oprd.7b00093.
1
H, 13C NMR, IR, and DSC data (PDF)

■ AUTHOR INFORMATION
Corresponding Authors
*E-mail: jesse.j.sabatini.civ@mail.mil. Phone: 410-278-0235.
*E-mail: pablo.e.guzman2.civ@mail.mil. Phone: 410-278-8608.
ORCID
Jesse J. Sabatini: 0000-0001-7903-8973
Author Contributions
P.E.G. and E.C.J. contributed equally to this work.
Notes
The authors declare no competing financial interest.

■ ACKNOWLEDGMENTS
The authors are indebted to the U.S. Army for financial support
in carrying out this work.

■ ABBREVIATIONS
KOH = potassium hydroxide; MeOH = methanol; H2SO4 =
sulfuric acid; DCM = methylene chloride; NaHCO3 = sodium
bicarbonate; NaOH = sodium hydroxide

■ REFERENCES
(1) Shipchandler, M. T. Synthesis 1979, 9, 666−686.
(2) Metz, A. E.; Kozlowski, M. C. J. Org. Chem. 2013, 78, 717−722.
(3) Cecchi, L.; De Sarlo, F.; Machetti, F. Eur. J. Org. Chem. 2006,
2006, 4852−4860.
(4) Alfa Aesar currently offers methyl nitroacetate at a price of $22.20
per gram.
(5) Zen, S.; Koyama, M.; Koto, S.; Ando, M.; Büchi, G. Org. Synth.
1976, 55, 776.
(6) NaOH was not as effective as KOH involving the dimerization of
nitromethane, thus resulting in significantly reduced yields.
(7) Lyttle, D. A. Chem. Eng. News 1949, 27, 1473.
(8) Snyder, R.; Witz, G.; Goldstein, B. D. Environ. Health Perspect.
1993, 100, 293−306.
(9) Ethyl acetate is a suitable extraction solvent. It was observed that
ethyl acetate carries over small amounts of impurities, presumably
from the esterification reaction, compared to dichloromethane. The
impurities were observed to be less generally than 1%.

1090 DOI: 10.1021/acs.oprd.7b00093

Org. Process Res. Dev. 2017, 21, 1088−1090