Organic Syntheses, CV 7, 114
Submitted by Miroslav Krumpolc and Jan Rocek
1.
Checked by D. Seebach, R. Dammann, F. Lehr, and M. Pohmakotr.
1. Procedure
In a
2-L, three-necked, round-bottomed flask equipped with a
reflux condenser are placed 250 mL of water,
48 mL (ca. 0.55 mol) of concentrated hydrochloric acid, and
49.5 g (0.65 mol) of cyclopropylcarbinol (Note
1); the reaction mixture is refluxed for ca. 100 min. The formation of
cyclobutanol can be observed nearly instantaneously, as this alcohol is only partially soluble in water and soon separates (Note
2). The flask is then immersed in an
ice bath equipped with a
mechanical stirrer, a
thermometer, and a
dropping funnel (using a three-way adapter, parallel sidearm), and the reflux condenser is replaced by an
ethanol–dry ice trap connected to a U-tube immersed in an ethanol–dry ice bath to ensure condensation of the very volatile
cyclobutanone. The flask is charged with an additional
48 mL (ca. 0.55 mol) of concentrated hydrochloric acid in 200 mL of water and
440 g (3.5 mol) of oxalic acid dihydrate (Note
1). The heterogeneous mixture is stirred for ca. 15 min to saturate the solution with
oxalic acid. A solution of
162 g (1.62 mol) of chromium trioxide in 250 mL of water is added dropwise with stirring at such a rate that the temperature of the reaction mixture is kept between 10°C and 15°C (
NaCl–ice bath, −5°C to −10°C) and the generation of
carbon dioxide remains gentle. The reduction of each drop of
chromic acid is practically instantaneous. As the addition of the reagent proceeds (1.5–2 hr),
oxalic acid gradually dissolves and a dark-blue solution containing chromium(III) salts results (Note
3). Just before the end of the oxidation (ca.
10 mL of the chromic acid solution left), the
cyclobutanone (with traces of
cyclobutanol) trapped in the
U-tube (a few milliliters) is added to the reaction mixture. After the oxidation is completed, the ice bath is removed and stirring is continued for ca. 1 hr to bring the reaction mixture to room temperature and to reduce the amount of
carbon dioxide in the solution.
The reaction mixture is poured into a
2-L separatory funnel and extracted with four
200-mL portions of methylene chloride (Note
4). The extracts (the lower phase) are combined, dried over anhydrous
magnesium sulfate containing a small amount of anhydrous
potassium carbonate (to remove traces of
hydrochloric acid), and filtered, and the filtrate is concentrated by distillation through a
vacuum-insulated silvered column (20-cm length, 1-cm i.d.) packed with
glass helices (size 2.3 mm, Lab Glass, Inc.) and equipped with an adjustable stillhead, until the pot temperature rises to 80°C (Note
5). The crude product is then transferred to a 100-mL flask and distilled through the same column (reflux ratio 10:1) to give
14–16 g (0.20–0.23 mol),
31–35% overall yield (based on pure
cyclopropyl carbinol) of
cyclobutanone, bp
98–99°C,
d254 0.926,
n25D 1.4190 (Note
6). The product is sufficiently pure (
98–99%) for most purposes (Note
5), (Note
7), (Note
8), and (Note
9).
2. Notes
3.
Oxalic acid is used in excess to ensure a rapid oxidation of the alcohol and to destroy the excess
chromic acid when the cooxidation process is over. Part of the
oxalic acid is consumed by
chromium(III) to form
oxalatochromium(III) complexes.
4. As
cyclobutanone is considerably soluble in water, a thorough and vigorous agitation is recommended to ensure good extraction of the aqueous layer by
methylene chloride.
Oxalic acid is insoluble in this solvent.
5. The checkers used a
silvered, vacuum-insulated column 30 cm in length with 1.5-cm i.d., filled with 4-mm × 4-mm helices; distillation of CH
2Cl
2 was first done from a
250-mL, two-necked flask with dropping funnel from which the dried extraction solution was continuously added. When ca. 50-mL total volume of solution remained (bath temperature ca. 90°C), it was transferred into a
100-mL, one-necked flask. Eight fractions of the
cyclobutanone were collected at a 15–20:1 reflux ratio: bp/g/% purity of ketone (by VPC): 80–90/1.17/37, 90–95/4.3/53, 95–96/1.71/99.5, 96–97/1.41/—, 96–97.5/1.2/99.9, 97.5–98/3.95/99.9, 98/3.76/100, 98/1.78/99.8. The
n20.5D of fraction 7 was 1.4210.
6. The reported physical constants of
cyclobutanone2 are bp 99–100°C,
d244 0.924,
n25D 1.4188.
7. Gas-liquid chromatography
[1/8-in. × 6-ft, 10% diethylene glycol succinate (LAC-728) column, 70°C] of
cyclobutanone (
99.2% pure) revealed the presence of small amounts of
methylene chloride (
0.6%) and
cyclobutanol (
0.2%). No cleavage product,
4-hydroxybutyraldehyde, was found. The traces of water, detected by NMR spectroscopy using CD
3COCD
3 as a solvent, can be removed by drying over molecular sieves.
8.
1H NMR (CCl
4) δ: 1.98, degenerate quintet (2 H,
J = 8 Hz); 3.03, t (4 H,
J = 8 Hz). IR (liquid film on KBr plates) cm
−1: 1783 (strong, C=O).
3. Discussion
Cyclobutanone has been prepared (1) by pyrolysis of
1-hydroxycyclobutane-1-carboxylic acid3 (15% yield), (2) by reaction of
diazomethane with ketene4,5,6 (36% overall yield based on precursors used for the generation of both components
6), (3) from
pentaerythritol, the final step being the oxidative degradation of
methylenecyclobutane7,8 (30–45% overall yield), (4) by oxidation of
cyclobutanol with
chromic acid–pyridine complex in
pyridine9 (no yield is given), (5) by oxidative cleavage of
5,9-dithiaspiro[3.5]nonane, prepared via
2-(ω-chloropropyl)-1,3-dithiane10,11 from
1,3-propanedithiol12 (
40% overall yield), (6) via solvolytic cyclization of
3-butyn-1-ol13,14 (30% yield), (7) by epoxidation of
methylenecyclopropane followed by ring expansion of resulting
oxaspiropentane15,16,17 (
28% overall yield), (8) from
1,3-dibromopropane and
methyl methylthiomethyl sulfoxide via
cyclobutanone dimethyl dithioacetal S-oxide18 (75% overall yield), and (9) from
4-chlorobutyraldehyde cyanohydrin, the final step being hydrolysis of
cyclobutanone cyanohydrin19 (
45% overall yield).
Cyclobutanone is a versatile starting material used for numerous synthetic and theoretical studies in the chemistry of small rings. The preparation of this compound by the cooxidation process illustrates the synthetic utilization of three-electron oxidation–reduction reactions.
This preparation is referenced from:
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