Org. Synth. 1977, 57, 36
DOI: 10.15227/orgsyn.057.0036
CYCLOBUTANONE FROM METHYLENECYCLOPROPANE via OXASPIROPENTANE
Submitted by J. R. Salaun, J. Champion, and J. M. Conia
1.
Checked by Z. Stojanac and Z. Valenta.
1. Procedure
Caution! Reactions and subsequent operations involving peracids and peroxy compounds should be run behind a safety shield. For relatively fast reactions, the rate of addition of the peroxy compound should be slow enough so that it reacts rapidly and no significant unreacted excess is allowed to build up. The reaction mixture should be stirred efficiently while the peroxy compound is being added, and cooling should generally be provided since many reactions of peroxy compounds are exothermic. New or unfamiliar reactions, particularly those run at elevated temperatures, should be run first on a small scale. Reaction products should never be recovered from the final reaction mixture by distillation until all residual active oxygen compounds (including unreacted peroxy compounds) have been destroyed. Decomposition of active oxygen compounds may be accomplished by the procedure described in Korach, M.; Nielsen, D. R.; Rideout, W. H. Org. Synth. 1962, 42, 50 (Org. Synth. 1973, Coll. Vol. 5, 414). [Note added January 2011].
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.
42.
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.
5.
tert-Butyl alcohol was refluxed overnight over
calcium hydride and distilled.
6.
The checkers obtained a heavy slurry at this stage which became heavier during addition of
3-chloro-2-methyl-1-propene. They found it necessary to dilute with more
tetrahydrofuran (about 450 ml. for the scale given in the procedure) before the
allyl chloride was added.
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.
9.
3-Chloro-2-methyl-1-propene (methallyl chloride) is available from Fluka A G and Eastman Organic Chemicals. The chloride, b.p.
72° (760 mm.), was distilled before use.
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).
214.
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.
16.
If the oil bath temperature reaches 80°, the residue consists of
cyclobutanone (
75%) and
oxaspiropentane (
25%). Distillation of this residue at 97–103° (760 mm.) yields
cyclobutanone and
oxaspiropentane; however, as reported
2 oxaspiropentane can be distilled at low temperature (36°) in vacuum (20 mm) without rearrangement.
17.
Caution! Addition of lithium iodide (catalytic amount) to a dichloromethane solution containing more than 30% oxaspiropentane leads to a very vigorous reaction.18.
Dichloromethane from the previous distillation is used.
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 method for the preparation of
cyclobutanone via oxaspiropentane is an adaptation of that reported by Salaün and Conia.
6 Although
cyclobutanone has been known now for over 75 years,
7 renewed interest in the potential of this small ring compound has led to several recently reported syntheses. The earlier syntheses of this compound consist of the reaction of the hazardous
diazomethane with ketene
8 and the oxidative degradation
9 or the ozonization of
methylenecyclobutane.
10 Recent syntheses involve the dithiane method of Corey and Seebach,
11,12 the solvolytic cyclization of
3-butyn-1-yl trifluoromethanesulfonate,
13 the ring enlargement of protected
cyclopropanone cyanohydrin14 and of
1-(phenylthio)cyclopropanemethanol,
15 and finally, the cyclodialkylation of
tosylmethyl isocyanide.
16 These methods are most or less laborious, time-consuming, and based on expensive starting materials. Most of them present the disadvantage of producing an aqueous solution of the highly water-miscible and volatile
cyclobutanone (b.p.
100°C).
The availability of
methylenecyclopropane, its facile oxidation to
oxaspiropentane, and the
lithium iodide-induced ring enlargement to
cyclobutanone described here remains the best laboratory scale preparation of
cyclobutanone. Furthermore, this rearrangement of oxaspiropentanes appears to be general for the preparation of substituted cyclobutanones.
2,17This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
m-chloroperbenzoic acid (MCPBA)
Oxaspiropentanes
4-nitroperbenzoic acid
sulfuric acid (7664-93-9)
ammonia (7664-41-7)
sodium thiosulfate (7772-98-7)
nitrogen (7727-37-9)
allyl chloride (107-05-1)
dichloromethane (75-09-2)
phenolphthalein (77-09-8)
magnesium sulfate (7487-88-9)
Diazomethane (334-88-3)
sodium amide (7782-92-5)
Tetrahydrofuran (109-99-9)
lithium aluminium hydride (16853-85-3)
3-buten-2-one (78-94-4)
2-methylpropenal (78-85-3)
tert-butyl alcohol (75-65-0)
calcium hydride (7789-78-8)
methallyl chloride,
3-chloro-2-methyl-1-propene (563-47-3)
lithium iodide (10377-51-2)
Cyclobutanone (1191-95-3)
methylenecyclobutane (1120-56-5)
Methylenecyclopropane (6142-73-0)
Oxaspiropentane (157-41-5)
4-nitrobenzoic acid (62-23-7)
4-nitroperoxybenzoic acid (943-39-5)
3-Butyn-1-yl trifluoromethanesulfonate (32264-79-2)
cyclopropanone cyanohydrin
1-(phenylthio)cyclopropanemethanol
tosylmethyl isocyanide (36635-61-7)
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