Organic Syntheses, CV 9, 314
Submitted by Lutz F. Tietze and Matthias Bratz
1.
Checked by Makoto Kaino and Hisashi Yamamoto.
1. Procedure
A
300-mL wash bottle with an inlet tube fitted with a wide pore glass frit and equipped with a stirring bar is charged with
40.0 g (0.18 mol) of dimethyl benzalmalonate (Note
1) dissolved in
150 mL of dichloromethane. The cooled solution (0°C,
ice bath) is purged with
argon (10 min) and then a stream of
ozone is passed through with vigorous stirring for 4.5 hr (Note
2). After the reaction is complete (TLC, silica gel,
diethyl ether/
petroleum ether = 1:1), excess
ozone is removed by purging with
argon (10 min) and
15 mL of dimethyl sulfide (Note
3) is slowly added at 0°C (
ice bath). Stirring is continued for 1 hr at this temperature and 2 hr at ambient temperature. Finally, air is blown through the solution for 12 hr (Note
4) and the residue is distilled at 20 mm, boiling range 90–100°C (Note
5) to give a yellow liquid that is further purified by filtration through
150 g of silica gel (SiO2) (Note
6) (elution with
diethyl ether). The solvent is removed under reduced pressure and the residue is recrystallized from
ethyl acetate to give
23.9 g (
80%) of the
dimethyl mesoxalate hydrate as colorless crystals (Note
7). Dehydration of the product is accomplished by azeotropic removal of water. The hydrate is dissolved in
dichloromethane (150 mL) and heated for 12 hr in a
Soxhlet apparatus (Note
8) equipped with a thimble containing layers of
phosphorus pentoxide and basic
alumina. The solvent is then evaporated and the residue distilled at reduced pressure to give
20.1 g (
76%) of the ester as a yellow liquid [bp
94°C (20 mm)].
2. Notes
1.
Dimethyl benzalmalonate and the corresponding esters of other alcohols can be prepared according to an Organic Syntheses procedure or as described in standard textbooks.
2 3
2. A
Fischer Ozonizator 502 was used. The flow was adjusted to about 70 L/hr and the
ozone content to 2–3 vol.%. The checkers used
Japan Ozone Co. Ltd. 0–3–2 Ozonator. The flow was adjusted to about 1.3 mmol/min. Efficiency of stirring affects the yield greatly.
3.
Dimethyl sulfide (Me2S) was purchased from Tokyo Kasei; it is also available from Aldrich Chemical Company, Inc.
5. Esters of higher alcohols may be filtered directly through silica gel and further purified by recrystallization.
6. Silica gel is 60 mesh.
7. All ester hydrates prepared were crystalline and can be stored without decomposition.
8. A
250-mL Soxhlet apparatus was used.
Waste Disposal Information
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
The method described is an improved procedure based on a work appearing in the patent literature.
4 Mesoxalates have been prepared by direct oxidation of malonates with
selenium dioxide (SeO2) or
nitrogen dioxide (N2O4),
5 6 7 by thermolysis of brominated malonates,
8 9 or by oxidative cleavage of malonates with
ozone10 11 or
singlet oxygen.
12 Diethyl mesoxalate is commercially available.
The procedure described has advantages over previously published methods. The starting material is easily obtained on a large scale at low cost. The ozonolysis can be conducted even on a large scale (150 g) and the workup is simple since the
benzoic acid that is also formed can be removed by distillation, chromatography, or crystallization. The method is general and can be applied to different esters including chiral derivatives such as
dimenthyl mesoxalate (see Table).
TABLE
PREPARATION OF DIALKYL MESOXALATES
|
|
Ester Hydrate |
|
R |
Yield [%] |
m.p.°C (Solvent) |
Ester b.p. [°C] |
|
Me |
77 |
76 (ethyl ether) |
110/17 mm |
i-Pr |
70 |
56–57 (t-BuOMe/pet. ether) |
96/10 mm |
Benzyl |
86 |
55–57 (t-BuOMe/pet. ether) |
(−) Menthyl |
74 |
115 (Et2O/pet. ether) |
(−)-Bornyl |
42 |
93–95 (Et2O/pet. ether) |
|
Mesoxalates are highly reactive substrates because of their strongly polarized carbon-oxygen bond. They have been used in pericyclic processes (e.g. Diels-Alder reactions,
13 14 15 16 17 ene reactions,
18 19 [3+2]
20 and [2+2]
21 cycloadditions), in aldol
22 and Wittig as well as Friedel-Crafts reactions.
23 Further applications arise from the use of the corresponding imines in hetero Diels-Alder reactions
24 25 and electrophilic cyclizations.
26 27 28 29 30
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