Organic Syntheses, Coll. Vol. 6, p.503 (1988); Vol. 57, p.60 (1977).
has been identified as a carcinogen; OSHA has issued emergency standards on its use. All procedures involving benzene
should be carried out in a well-ventilated hood
, and glove protection is required.
A 1-l., three-necked, round-bottomed flask
equipped with a calcium chloride drying tube
, a mechanical stirrer
, and a ground-glass stopper
is charged with 28.2 g. (0.184 mole) of freshly distilled methyl bromoacetate
, 500 ml. of anhydrous N,N-dimethylacetamide (Note 1)
, and 20.0 g. (0.168 mole) of methyl nitroacetate (Note 2)
. The solution is stirred vigorously while 146 ml. (0.168 mole) of 1.15 N sodium methoxide
is added in one portion. The resulting light-yellow suspension is stirred for an additional 16 hours at room temperature during which time it changes into a clear yellow solution.
After dilution with 200 ml. of benzene
, the solution is transferred to a 2-l. separatory funnel
containing 800 ml. of ice water and shaken thoroughly. The aqueous layer is separated, acidified to pH 3–4 with 2–3 ml. of concentrated hydrochloric acid
, and extracted with three 100-ml. portions of benzene
. All the organic layers are combined and dried over anhydrous sodium sulfate
. Filtration and concentration of the solution with a rotary evaporator
, followed by exposure to high vacuum for 2–3 hours, affords 17.3–19.3 g.
of the crude product (Note 3)
. Low-boiling impurities are removed by vacuum distillation (Note 4)
, the residual oil (14–15 g.
) is transferred to a 50-ml. flask
equipped with a short-path distillation apparatus
, and vacuum distillation is continued. A forerun is taken until no rise in boiling point is observed before 7.2–8.5 g.
) of dimethyl nitrosuccinate
is collected as a colorless oil, b.p. 85° (0.07 mm.)
1.4441 (Note 5)
was treated with molecular sieves for 2 days, decanted, and distilled under reduced pressure, b.p. 85° (30 mm.)
, before use.
The bath temperature should be maintained below 70–75°. Distillation was carried out using a Claisen head
, and the receiving flasks were immersed in ice.
The checkers found it convenient to omit this distillation and the subsequent transfer. Instead the crude product was placed in a 25-ml. flask and carefully distilled (0.07 mm). The bath temperature was raised slowly, and a forerun was collected until the boiling point stabilized.
The distilled product was determined by the checkers to be 85–90% pure (GC analysis), the major impurity being the doubly alkylated by-product. Purity can be increased to 95% by redistillation. The checkers found that conducting the experiment on a
scale resulted in increased yield (34%
) and purity (90–93%) of once-distilled product.
For twice-distilled material: IR (liquid film) cm.−1: 1745 strong, 1565 strong, 1430 medium strong; 1H NMR (CDCl3), δ (multiplicity, coupling constant J in Hz., number of protons): 3.14–3.45 (m, 2H), 3.76 (s, 3H), 3.86 (s, 3H), 5.6 (d of d, J = 6 and 8, 1H).
The present method is a simple, one-step procedure employing commercially available or readily accessible starting materials. Other α-nitro carboxylic esters may be prepared in this way;4
for example, dimethyl 2-nitropentanedioate
was prepared in 45–50%
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