Organic Syntheses, CV 6, 320
Submitted by J. R. Salaun, J. Champion, and J. M. Conia
1.
Checked by Z. Stojanac and Z. Valenta.
1. Procedure
Caution! The preparation of
methylenecyclopropane must be carried out in an
efficient hood because
ammonia is evolved.
Oxaspiropentanes have been widely used as useful synthetic intermediates and appear to be quite stable; nevertheless, in view of the nature of the compounds, it is recommended that the preparation and handling of
oxaspiropentane be carried out behind a safety screen.
A.
Methylenecyclopropane (Note
1). A dry,
3-l., three-necked, round-bottomed flask with ground-glass fittings is equipped with a sealed
stirrer (Note
2) driven by a
heavy-duty motor, an
efficient condenser fitted with a
silica gel drying tube, and a
500-ml., pressure-equalizing dropping funnel connected to a
nitrogen inlet. The flask is charged with
450 g. (11.5 moles) of sodium amide (Note
3) and
750 ml. of anhydrous tetrahydrofuran (Note
4), and the
dropping funnel with a solution of
283.5 g. (3.831 moles) of anhydrous tert-butyl alcohol (Note
5) in
300 ml. of anhydrous tetrahydrofuran While the
sodium amide suspension is stirred vigorously under a
nitrogen atmosphere, the solution of
tert-butyl alcohol is added dropwise at room temperature over 3 hours. The stirred mixture is heated to 45°, with an
oil bath, for 2 hours, at which point it may be necessary to add additional
tetrahydrofuran (Note
6). The outlet of the condenser is connected with an adapter to a
250-ml. gas washing bottle containing
100 ml. of 5 N sulfuric acid, to eliminate evolved
ammonia (Note
7). A
silica gel drying tube (15 cm. long) joins the gas washing bottle to a
300-ml. cold trap protected from the atmosphere with a
calcium chloride drying tube and cooled in a
methanol–dry-ice bath maintained at −80° (Note
8). A solution of
228 g. (2.52 moles) of 3-chloro-2-methyl-1-propene (Note
9) in
500 ml. of dry tetrahydrofuran is added to the stirred basic mixture, which is then heated to 65° over a period of approximately 8 hours; a light
nitrogen stream is used to carry the
methylenecyclopropane into the cold trap. After the addition is complete, the reaction mixture is stirred and heated to 65° for 3 more hours (Note
10). The trap flask contains
58 g. (
43%) of
methylenecyclopropane (Note
11).
B.
Oxaspiropentane. A 3-l., three-necked, round-bottomed flask equipped with a sealed stirrer, a
thermometer, and an efficient condenser cooled by methanol–dry ice (Note
12) is charged with
450 ml. of dichloromethane and
200 g. (1.09 moles) of 4-nitroperbenzoic acid (Note
13). The mixture is stirred and cooled to −50° by immersion of the flask in a methanol–dry-ice bath before
58 g. (1.1 moles) of methylenecyclopropane is distilled directly into the flask with a
gas-inlet tube reaching to the bottom of the flask. The cooling bath is removed so that the temperature gradually rises; at about 0° the exothermic reaction starts. The temperature is maintained below 20° by occasional immersion of the flask in an
ice–water bath; the
methylenecyclopropane is allowed to reflux slowly (Note
14). After refluxing stops, the mixture is stirred overnight at room temperature. The
4-nitrobenzoic acid is removed by filtration and washed twice with
100-ml. portions of dichloromethane. The combined organic layers, which still contain about 10% of the total amount of
4-nitrobenzoic acid, are distilled at room temperature under reduced pressure (15 mm.) to eliminate the acid completely (Note
15). The distillate is concentrated to
ca. 200 ml. of dichloromethane by distillation through a
15-cm., helix-packed, vacuum-insulated column, at a maximum oil bath temperature of 60° (Note
16).
C.
Cyclobutanone (Note
16). The resulting solution of
oxaspiropentane (35%) in
200 ml. dichloromethane is added dropwise at room temperature to a magnetically stirred solution containing
5–10 mg. of lithium iodide in
50 ml. of dichloromethane (Note
17), (Note
18), at such a rate as to maintain gentle reflux of the solvent. After the addition, when the reaction mixture returns to room temperature, the transformation into
cyclobutanone is complete. The
dichloromethane solution is washed with
20 ml. of saturated aqueous sodium thiosulfate and 20 ml. of water, dried over
magnesium sulfate, and concentrated by distillation of the solvent through a 15-cm., helix-packed, vacuum-insulated column. The residual liquid consists of
cyclobutanone (
95%) and
3-buten-2-one and
2-methylpropenal (5%).
2 A final distillation at 760 mm. through a
50-cm., stainless-steel spinning band column yields
41 g. (
64% from
methylenecyclopropane) of pure
cyclobutanone, b.p.
100–101° (Note
19), (Note
20).
2. Notes
1. The procedure described for the synthesis of
methylenecyclopropane is patterned after the method reported by Caubere and Coudert.
3 Methylenecyclopropane is also available from the stepwise method described by Köster and co-workers.
4
2. The checkers used a stirrer for vacuum work (Teflon bearing, Fisher Scientific Company). The submitters used a
mercury-sealed stirrer.
3. The submitters used
sodium amide (obtained from Fluka A G as small lumps under kerosene) which was washed with anhydrous
tetrahydrofuran and ground with a mill. The checkers used freshly opened and recently purchased cans of
sodium amide powder (Fisher Scientific Company); older reagent gave unsatisfactory results.
7. It is advisable to insert a safety bottle to avoid any run-back of
sulfuric acid into the reaction flask. The gas washing bottle must be cooled by immersion in a large
water bath (15°); the
sulfuric acid solution is replaced by a fresh 5
N solution when neutralized by evolved
ammonia (checked by
phenolphthalein).
8.
Methylenecyclopropane, b.p.
11° (760 mm.), is volatile at room temperature; all adapter fittings must be carefully checked. The checkers recommend the use of two cold
traps in series.
10. In the checkers' hands, at least 24 hours was needed to produce the bulk of
methylenecyclopropane; small amounts of the product condenser during an additional 24-hour period.
11. The yield is determined by weighing the cold trap before and after distillation of
methylenecyclopropane. Any small amounts of
tetrahydrofuran carried into the
methylenecyclopropane trap are eliminated in a subsequent distillation. By
1H NMR analysis the checkers found that no
tetrahydrofuran reached the cold traps; the spectrum (CD
2Cl
2) shows a triplet at δ 1.00 and a quintuplet at δ 5.35 in the ratio 4:2.
12.
Caution! The yield isolated from this reaction depends on the efficiency of this condenser; the epoxidation is exothermic and methylenecyclopropane is volatile.
13. The
4-nitroperoxybenzoic acid (technical, 77–85%) may be obtained from the Aldrich Chemical Co., Inc., or Fluka A. G. (or from its U.S. representative, Tridom Chemical Inc.), or may be prepared from
4-nitrobenzoic acid.
5 The oxidation of
methylenecyclopropane to
oxaspiropentane has been reported to proceed in the same manner, in 48% yield, with the less expensive reagent
m-chloroperbenzoic acid (MCPBA).
2
14. Cooling below 0° stops the reaction.
15. A short-path distillation apparatus is used, the distillate (
oxaspiropentane plus
dichloromethane) being trapped in a receiver placed in a methanol–dry-ice bath cooled to −80°. The checkers found it useful to drive out last traces of product by adding several milliliters of
dichloromethane to the residual thick paste and distilling. The
1H NMR spectrum (CD
2Cl
2) shows an octet at δ 0.85 and a singlet at δ 3.00 in the ratio 4:2.
19. The purity of
cyclobutanone was checked by
GC on a 3.6-m. column containing 20% silicone SE-30 on chromosorb W at 65°. The IR spectrum (neat) shows carbonyl absorption at 1779 cm.
−1; the
1H NMR spectrum (CCl
4) shows a multiplet at δ 2.00 and a triplet at δ 3.05 in the ratio 1:2.
20. The checkers obtained yields of
61–64% on smaller-scale runs (
10 g. of
cyclobutanone).
3. Discussion
This preparation is referenced from:
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