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DOI:10.15227/orgsyn.069.0205

Organic Syntheses, Coll. Vol. 8, p.116 (1993); Vol. 69, p.205 (1990).

7-CHLORO-7-CYANOBICYCLO[4.2.0]OCTAN-8-ONE[(Prepared from Chlorocyanoketene) (Bicyclo[4.2.0]octane-7-carbonitrile, 7chloro-8-oxo-, (1α,6α,7β)-)]Submitted by Paul L. Fishbein and Harold W. Moore1.
Checked by Steven Wolff and David L. Coffen.

1. Procedure
A. 3,4-Dichloro-5-isopropoxy-2(5H)-furanone.2 A 1-L, round-bottomed flask equipped with aDean–Stark trap, a condenser, an argon bubbler, and a magnetic stirrer is charged with 50.7 g (0.30 mol)of mucochloric acid (Note 1), 46 mL (0.60 mol) of isopropyl alcohol, 300 mL of toluene, and 20 dropsof concentrated sulfuric acid. The mixture is heated to reflux with stirring overnight ( 18 hr) withseparation of water. The solution is cooled, washed with saturated sodium bicarbonate solution andbrine, and dried with magnesium sulfate. After removal of the solvent under reduced pressure, theresidue is distilled to give 60.88 g (96%) of the furanone as a clear colorless liquid (bp 90–91°C, 1.5mm; lit.2 mp 23–24°C, bp 109–111°C, 6 mm).
B. 7-Chloro-7-cyanobicyclo[4.2.0]octan-8-one. To a 250-mL Erlenmeyer flask is added 20.0 g(94.8 mmol) of 3,4-dichloro-5-isopropoxy-2(5H)-furanone and 120 mL of methanol. The flask is cooled
in an ice bath with stirring and 7.5 g (115.4 mmol) of sodium azide is added. The ice bath is removed
after 15 min and the mixture is stirred for an additional 50 min. After dilution with 600 mL of water, thereaction mixture is extracted with one 100-mL and two 50-mL portions of toluene. The combinedorganic layers are washed with water (2 × 100 mL) and with 100 mL of brine and are dried withmagnesium sulfate. TLC analysis (1 : 1 ether:hexane, SiO2) indicates only one component (Rf = 0.38)
and no remaining dichlorofuranone (Rf = 0.45) (Note 3).

A 2-L, three-necked flask fitted with condenser, argon bubbler, thermometer, and addition funnel ischarged with 700 mL of toluene (freshly distilled and dried over Linde 4A molecular sieves) and 20 mL(Note 4) of cyclohexene (freshly distilled). With magnetic stirring, the mixture is heated to 105°C andthe azidofuranone solution prepared above is added over a period of 20 min (Note 5). On completion,
the reaction mixture is heated for an additional 1.25 hr at 105°C. The solution is cooled andconcentrated under reduced pressure to yield a yellow-brown residue that is distilled using a short-path
apparatus to give 13.3 g (76%) (bp 85–90°C, 0.5 mm) of the cyclobutanone as a very pale-yellow oilthat solidifies (mp 34–35°C) on standing at 4°C (Note 6) and (Note 7).

2. Notes
1. Practical-guide mucochloric acid obtained from Aldrich Chemical Company, Inc. (mp 125–128°C)
was used. Unless otherwise stated, all reagents and solvents were of commercial grade. The checkers
used mucochloric acid obtained from Eastman Organic Chemicals.
2. The spectral properties are as follows: IR (CCl4) cm−1: 1795, 1652; 1H NMR (CDCl3) δ: 1.31 (d, 6 H,J = 6.2), 4.14 (heptet, 1 H, J = 6.2), 5.87 (s, 1 H); MS (EI): 195 (39), 151 (100), 95 (25); MS (Cl): 211(M+ + 1), 100. Anal. calcd. for C7H8Cl2O3: C, 39.84; H, 3.82. Found: C, 39.55; H, 3.84.
3. The submitters isolated and characterized the azidofuranone as a white crystalline solid after
recrystallization from petroleum ether (bp 35–60°C), with mp 51.5–52.5°C. The spectral properties areas follows: IR (CCl4) cm−1: 2130, 1814, 1664; 1H NMR (CDCl3) δ: 1.33 (d, 6 H, J = 6.2), 4.17 (heptet, 1H, J = 6.2), 5.99 (s, 1 H); MS (EI): 217 (M+, 6), 158 (34), 119 (28, C3ClNO + H2O), 101 (77), 73 (100);
MS (Cl): 218 (M+ + 1, 55), 120 (10, C3HClNO + H2O), 102 (100). Anal. calcd. for C7H8ClN3O3: C,38.64; H, 3.71. Found: C, 38.67; H, 3.65. The azidofuranone decomposes at about 80°C, so caution
must be exercised when working with it.
4. If an alkene less volatile than toluene is used, 1.1–1.2 equiv of the alkene are satisfactory.
5. The ketene must be generated in situ since it is exceptionally reactive and will undergo selfcondensation if permitted.
6. Recrystallization from petroleum ether (35–60°C) in a dry ice/acetone bath afforded colorless crystals
with mp 39.5–40.5°C. The spectral properties are as follows: IR (CCl4) cm−1: 2340, 1838: 1H NMR(CDCl3) δ: 1.66 (m, 8 H), 3.03 (m, 1 H), 3.96 (m, 1 H); 13C NMR (CDCl3): 20.72, 21.20, 21.41, 24.25,36.26, 55.33, 64.17, 115.90, 189.91; MS (EI): 183 (M+, 6), 148 (46), 119 (13), 109 (33), 81 (100); MS(Cl): 184 (M+ + 1, 84), 156 (100). Anal. calcd. for C9H10ClNO: C, 58.87; H, 5.49. Found: C, 58.58; H,5.71.
7. Since chlorocyanocyclobutanones are readily hydrolyzed, protic recrystallization solvents and silica
gel chromatography should be avoided. Short-path distillation is the method of choice for thepurification of most of the cyclobutanones.

3. Discussion
Chlorocyanoketene has been prepared previously by the thermal decomposition of thepseudomethyl ester of the azidofuranone.3 4 5 This azide has been used extensively withoutcomplication. However, all azides are capable of detonation. The ratio (C + O/N) has been suggested asa threshold value for detonation, which may occur when this ratio is lower than 3:1.6 The ratio for thepreviously used azide is 2.7, while that for the isopropyl analog is 3.3:1.
The synthesis of chlorocyanoketene presented here has advantages over other routes such as
dehydrohalogenation of the appropriate acid chloride.7 The most obvious advantage is that the ketene isgenerated slowly during thermolysis. Thus, its concentration is always low. In addition, since it isgenerated by pyrolytic means, the presence of tert-amines and/or metals is avoided. No other method forthe synthesis of chlorocyanoketene has been reported. However, we have found that it can be preparedwith difficulty from chlorocyanoacetyl chloride.
Chlorocyanoacetyl chloride can be made from the extremely hygroscopic acid. It is quite unstable,with 1 g decomposing in 1 hr at room temperature. If a mixture of an imine and triethylamine is treatedwith the acyl chloride, only a dark tar is obtained. However, if the acyl chloride is first treated with theimine, the reaction allowed to subside, and the mixture then treated with triethylamine, the resulting 2azetidinone is formed in 63% yield. This is in comparison with the 96% yield obtained by using theazidofuranone.
Other cyclobutanones that can be made with chlorocyanoketene and their respective yields areshown in Table I.

TABLE IOTHERCYCLOBUTANONESFROMCHLOROCYANOKETENE4c
80%

86%

74%

86%

93%

30%67%

70%

References and Notes
1. Department of Chemistry, University of California, Irvine, CA 92717.
2. The procedure for making the pseudoester is from Hachihama, Y.; Shono T. J. Chem. Soc.,
Japan, Ind. Chem. Sect. 1955, 58, 692; Chem. Abstr. 1956, 50, 12015e..
3. Moore, H. W.; Hernandez, L.; Sing, A. J. Am. Chem. Soc. 1976, 98, 3728;

4. Kunert, D. M.; Chambers, R.; Mercer, F.; Hernandez, L., Jr.; Moore, H. W. Tetrahedron Lett.
1978, 929;
5. Fishbein, P. L.; Moore, H. W. J. Org. Chem. 1984, 49, 2190.
6. Biffin, M. E. C.; Miller, J.; Paul, D. B. "Introduction of the Azido Group" in "The Chemistry ofthe Azido Group," Patai, S., Ed.; Wiley: New York, 1971, p. 61.
7. Ward, R. W. "The Preparation of Ketenes" in "The Chemistry of Ketenes, Allenes, and Related
Compounds, Part 1," Patai, S., Ed.; Wiley: New York, 1980, pp. 223–227.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);(Registry Number)petroleum etherbrine
SiO2
Bicyclo[4.2.0]octane-7-carbonitrile, 7-chloro-8-oxo-, (1α,6α,7β)-)sulfuric acid (7664-93-9)
methanol (67-56-1)
ether (60-29-7)
sodium bicarbonate (144-55-8)
Cyclohexene (110-83-8)
toluene (108-88-3)
isopropyl alcohol (67-63-0)
sodium azide (26628-22-8)
magnesium sulfate (7487-88-9)
hexane (110-54-3)
triethylamine (121-44-8)
2-azetidinone (930-21-2)
7-Chloro-7-cyanobicyclo[4.2.0]octan-8-one (89937-15-5)
Chlorocyanoketene
mucochloric acidazidofuranone
chlorocyanoacetyl chloride
3,4-Dichloro-5-isopropoxy-2(5H)-furanone (29814-12-8)
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