Checked by James Cason and Robert B. Hutchison.
1. Procedure
A.
Methyl 5,5-dimethoxy-3-methyl-2,3-epoxypentanoate. A
2-l. three-necked flask is equipped with a
sealed centrifugal stirrer (Note
1), a
thermometer inserted through an adapter with a side arm connected to a source of dry
nitrogen, and a
250-ml. Erlenmeyer addition flask.2 The apparatus is dried with a free flame in a slow stream of
nitrogen; from this point the reaction is conducted in an atmosphere of
nitrogen (Note
2).
A mixture of
132 g. (1.0 mole) of 4,4-dimethoxy-2-butanone (Note
3),
174 g. (1.6 moles) of methyl chloroacetate (Note
3), and
800 ml. of dry ether is placed in the reaction flask, then
86 g. (1.6 moles) of sodium methoxide (Note
4) is placed in the addition flask. The solution is cooled in an
ice-salt bath to −10°, then the
sodium methoxide is added gradually at a rate such that a temperature below −5° can be maintained (about 2 hours). The mixture is stirred for an additional 2 hours (Note
5) and then allowed to come to room temperature overnight. It is cooled again to 0° and made slightly acidic by the addition of a solution of
10 ml. of glacial acetic acid in 150 ml. of water. The
ether is decanted, and the residual slurry is extracted with three
100-ml. portions of ether. The combined
ether solutions are washed in a
separatory funnel with
50 ml. of saturated sodium chloride solution to which is added
1-g. portions of sodium bicarbonate until the washings are no longer acidic. After each
bicarbonate addition, the mixture is shaken for at least 1 minute before a test for acidity is made. Finally, the
ether phase is washed with saturated
sodium chloride solution, then dried over
20–25 g. of anhydrous magnesium sulfate. Distillation of the solvent leaves a nearly quantitative yield of crude glycidic ester (Note
6).
B.
Methyl 3-methyl-2-furoate. The crude glycidic ester prepared as described above is placed in a
300-ml. flask which is attached to a
12-cm. column filled with 3/16-inch glass helices (or a 50-cm. simple Vigreux column) and heated in a liquid bath. When the pot temperature reaches about 160°, or before,
methanol begins to distil. Heating is continued until the distillation of
methanol essentially ceases and about the theoretical amount (64 g.) has been collected. After the heating bath has been allowed to cool, the product is distilled at reduced pressure; b.p.
72–78°/8 mm., yield
91–98 g. (
65–70%) (Note
7). The ester solidifies in the
receiver as an essentially pure compound, m.p.
34.5–36.5° (Note
8).
2. Notes
1. A stirring assembly which makes use of a lubricated ball-joint seal
3 is convenient. The checkers used a Hershberg stirrer rather than a centrifugal stirrer.
2. Maintenance of a low positive pressure of
nitrogen on the system is accomplished by insertion of a T-tube in the
nitrogen line for attachment of a U-tube whose bend is just closed with mineral oil.
4. The submitter reports that the commercial 95% "
Sodium Methylate" from Mathieson Chemical Corp. is satisfactory, provided that either fresh material or material which has been opened previously only under dry
nitrogen is used. The checkers experienced such erratic results with commercial
sodium methoxide (even previously unopened bottles) that freshly prepared material was used. For this purpose,
37 g. of clean sodium, cut in 1- to 3-g. pieces, was added portionwise to
800 ml. of stirred anhydrous methanol contained in a
2-l. three-necked flask equipped with a condenser. After the
sodium had dissolved, the
methanol was removed by distillation at reduced pressure, and the residual white
sodium methoxide was dried by heating at 150° under aspirator vacuum.
5. The stream of
nitrogen may be discontinued at this point if the outlet tube from the flask is closed with a
Drierite tube.
6. The submitter reports that the residual glycidic ester was distilled through a
15-cm. Vigreux column to yield
185–195 g. of crude product, b.p.
113–122°/8 mm. Redistillation through a
25-cm. column packed with 3/16-inch glass helices was reported to give
157–164 g. (
77–80%) of product; b.p.
93°/0.7 mm. to 89°/1 mm.;
nD25 1.4405–1.4419. The drop in boiling point was attributed to decomposition during distillation to yield
methanol and
methyl 3-methyl-2-furoate. The checkers found that in most runs the product obtained from the first distillation consisted largely of the
furoate.
7. In a run 15 times this size, a 71% yield was obtained by the submitter.
8. Recrystallization from
ethanol raises the melting point to 36.5–37°.
3. Discussion
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
Drierite
ethanol (64-17-5)
acetic acid (64-19-7)
methanol (67-56-1)
ether (60-29-7)
sodium bicarbonate (144-55-8)
sodium chloride (7647-14-5)
nitrogen (7727-37-9)
chloroacetate (79-11-8)
sodium methoxide,
sodium methylate (124-41-4)
sodium (13966-32-0)
methyl chloroacetate (96-34-4)
magnesium sulfate (7487-88-9)
bicarbonate (71-52-3)
Methyl 3-methyl-2-furoate,
2-Furoic acid, 3-methyl-, methyl ester (6141-57-7)
4,4-dimethoxy-2-butanone,
3-ketobutyraldehyde dimethyl acetal (5436-21-5)
4-methoxy-3-buten-2-one
furoate
methyl 5,5-dimethoxy-3-phenyl-2,3-epoxypentanoate
Methyl 5,5-dimethoxy-3-methyl-2,3-epoxypentanoate
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