A Publicationof Reliable Methods
for the Preparationof Organic Compounds

Working with Hazardous Chemicals
The procedures in Organic Syntheses are intended for use only by persons with proper
training in experimental organic chemistry. All hazardous materials should be handledusing the standard procedures for work with chemicals described in references such as"Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C.,
2011;
thefulltext
canbeaccessed
freeofchargeathttp://www.nap.edu/catalog.php?record_id=12654).
All chemical waste should be
disposed of in accordance with local regulations. For general guidelines for themanagement of chemical waste, see Chapter 8 of Prudent Practices.
In some articles in Organic Syntheses, chemical-specific hazards are highlighted in red“Caution Notes” within a procedure. It is important to recognize that the absence of acaution note does not imply that no significant hazards are associated with the chemicals
involved in that procedure. Prior to performing a reaction, a thorough risk assessment
should be carried out that includes a review of the potential hazards associated with eachchemical and experimental operation on the scale that is planned for the procedure.
Guidelines for carrying out a risk assessment and for analyzing the hazards associatedwith chemicals can be found in Chapter 4 of Prudent Practices.
The procedures described in Organic Syntheses are provided as published and areconducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board ofDirectors do not warrant or guarantee the safety of individuals using these procedures andhereby disclaim any liability for any injuries or damages claimed to have resulted from orrelated in any way to the procedures herein.

These paragraphs were added in September 2014. The statements above do not supersede any specifichazard caution notes and safety instructions included in the procedure.

DOI:10.15227/orgsyn.069.0199

Organic Syntheses, Coll. Vol. 8, p.306 (1993); Vol. 69, p.199 (1990).

A GENERAL SYNTHESIS OF CYCLOBUTANONES FROMOLEFINS AND TERTIARY AMIDES: 3HEXYLCYCLOBUTANONE

Submitted by C. Schmit, J. B. Falmagne, J. Escudero, H. Vanlierde, and L. Ghosez1.
Checked by Thomas J. Sowin and Albert I. Meyers.

1. Procedure
A 500-mL, three-necked flask is equipped with a rubber septum, a magnetic stirring bar, a gas inlet,
and a reflux condenser. The top of the condenser is connected to a pressure-equalizing dropping funnel
isolated from moisture by a sulfuric acid trap (Note 1). The flask is cooled to −15°C and charged with
N,N-dimethylacetamide (3.26 g, 37.5 mmol) (Note 2) in 100 mL of 1,2-dichloroethane (Note 3). The
dropping funnel is charged with 1-octene (16.8 g, 150 mmol) (Note 4) and 2,4,6-collidine (5.44 g, 45mmol) (Note 5) in 50 mL of 1,2-dichloroethane. A slightly positive pressure of argon is maintained in
the apparatus throughout the course of the reaction. Trifluoromethanesulfonic anhydride (12.69 g, 45mmol) (Note 6) is added through the rubber septum into the solution of N,N-dimethylacetamide bymeans of a syringe. A precipitate is formed. The olefin–collidine solution is then added dropwise over a20-min period. During these operations rapid stirring and cooling are maintained. The resulting mixture
is refluxed for 17 hr (Note 7). The solvent is removed by rotary evaporation. The oily residue is washedwith dry ether (3 × 20 mL) (Note 8). Then 20 mL of carbon tetrachloride (Note 9) and 20 mL of water
are added to the crude cyclobutaniminium salt. The mixture is refluxed for 6 hr (Note 10). The organic
phase is separated and the aqueous phase is extracted with carbon tetrachloride (3 × 20 mL). The
combined organic phases are dried over anhydrous magnesium sulfate. The solvent is removed bydistillation at atmospheric pressure (Note 11). Bulb-to-bulb distillation (bath temperature 100–110°C,water pump) gives 3.3 g (59%) of 3-hexylcyclobutanone (Note 12) and (Note 13).

2. Notes
1. The assembled apparatus is flame-dried under a slight pressure of argon.
2. N,N-Dimethylacetamide (Janssen Chimica, Beerse, Belgium) is distilled before use. The checkers
used it as obtained from Aldrich Chemical Company, Inc.
3. 1,2-Dichloroethane (99%) is obtained from Janssen Chimica or Aldrich Chemical Company, Inc. It isdistilled from calcium hydride.
4. 1-Octene (97%) is purchased from Janssen Chimica or Aldrich Chemical Company, Inc. and distilled.
5. 2,4,6-Collidine (99%, Janssen Chimica or Aldrich Chemical Company, Inc.) is distilled from calciumhydride and stored under argon in a brown bottle.
6. Trifluoromethanesulfonic anhydride is prepared just prior to use according to the procedure of Stangand Dueber.2 The checkers obtained it from Aldrich Chemical Company, Inc.
7. During this period the solution turns dark brown and, after rotary evaporation, the residue is a thick,black oil. The progress of the reaction can be followed by IR () cm−1: 1730–1735, but the checkers found that it was complete in this 17-hr period.
8. Technical ether is dried over potassium hydroxide.
9. Technical carbon tetrachloride is used. Dichloromethane is preferred only when the cyclobutanone is
too volatile.
10. The progress of the hydrolysis can be followed by IR, but the checkers found that it was complete in
6 hr.
11. Rotary evaporation or vacuum distillation can lead to a substantial loss of cyclobutanone.
12. The spectral properties of the compound are as follows: IR (CCl4, νC=O) cm−1 1785; 1H NMR (270MHz, CDCl3) δ: 0.840 (t, 3 H, CH3), 1.226–1.243–1.302 (m, 8 H, CH2), 1.513 (m, 2 H, CH), 2.300 (m,1 H, CH), 2.610 (m, 2 H, CH), 3.079 (m, 2 H, CH); 13C NMR (75.5 MHz, CDCl3) δ: 13.98, 22.53,23.78, 28.16, 29.02, 31.71, 36.29, 52.43, 208.61.
13. The physical properties of the semicarbazone are as follows: mp 148.5°C; Anal. calcd. for
C11H21N3O: C, 62.53; H, 10.02; N, 19.88; O, 7.57. Found: C, 62.63; H, 10.05; N, 19.95; O, 7.50.

3. DiscussionCyclobutanones are important synthetic intermediates. A common synthetic method for their
preparation is the [2+2] cycloaddition of olefins with ketenes often generated in situ from acidchlorides. However, that method suffers limitations especially when aldoketenes and unreactive olefins
are used.
Keteniminium salts are more electrophilic than ketenes and are thus able to react with lessnucleophilic olefins. Ketoketeniminium salts can be conveniently prepared from the corresponding αchloroenamines and Lewis acids.3 4 5 6 However, the method cannot be applied well to the preparation of
the less stable aldoketeniminium salts.
The method described here which involves the in situ generation of keteniminium triflates ispractical and more general. The best results were obtained with 2,4,6-collidine, but occasionally themore expensive 2,6-di-t-butyl-4-methylpyridine was superior. Pyridine gave satisfactory results in few
cases only. Triethylamine always gave poor results. With the more reactive olefins (e.g., styrene),reactions can be run in refluxing dichloromethane. The procedure described here usually gives better
yields than that previously reported in a preliminary communication.10 It has been used to prepare
cyclobutanones as well as cyclobutenones7,8 9 from a wide variety of olefins or acetylenes. A few
examples are shown in Table I. The method works well for olefins or acetylenes bearing alkyl, alkenyl
or aryl groups. It does not apply to enol ethers or enamines.

TABLE ISYNTHESIS OF CYCLOBUTANONES FROM TERTIARY AMIDES AND OLEFINSAmide

CH3CH2CON(CH3)2

CH3CH2CON(CH3)2

OlefinCyclobutanone

Cyclohexeneα-Yield(%)

89a79aMethylstyrene

CH3CH2CON(CH3)2Allyl ethylether

56a

CH3CON(CH3)2

Cyclohexene

46

CH3CON(CH3)2

Styrene7187b(H3C)2NCO(CH2)6CH=CH271b

Mixture of endo + exo isomers.
These reactions were performed underslightly different conditions.10ab

References and Notes
1. Laboratoire de Chimie Organique de Synthèse, Université Catholique de Louvain, Place Louis
Pasteur 1, B-1348, Louvain-La-Neuve, Belgium.
Stang,P. J.; Dueber, T. E. Org. Synth., Coll. Vol. VI 1988, 757.
2.
Marchand-Brynaert,J.; Ghosez, L. J. Am. Chem. Soc. 1972, 94, 2870;
3.
4. Sidani, A.; Marchand-Brynaert, J.; Ghosez, L. Angew. Chem., Int. Ed. Engl. 1974, 13, 267;
5. Houge, C.; Frisque-Hesbain, A. M.; Mockel, A.; Declercq, J. P.; Germain, G.; Van Meersche, M.
J. Am. Chem. Soc. 1982, 104, 2920;
6. Saimoto, H.; Houge, C.; Hesbain-Frisque, A.-M.; Mockel, A.; Ghosez, L. Tetrahedron Lett.
1983, 24, 2251.
7. Falmagne, J.-B.; Escudero, J.; Talbe-Sahraoui, S.; Ghosez, L. Angew. Chem., Int. Ed. Engl. 1981,20, 879.
8. Hoornaert, C.; Hesbain-Frisque, A. M.; Ghosez, L. Angew. Chem., Int. Ed. Engl. 1975, 14, 569;
9. Schmit, C.; Sahraoui-Taleb, S.; Differding, E.; Dehasse-De Lombaert, C. G.; Ghosez, L.
Tetrahedron Lett. 1984, 25, 5403.
10. Markó, I.; Ronsmans, B.; Hesbain-Frisque, A. M.; Dumas, S.; Ghosez, L.; Ernst, B.; Greuter, H.
J. Am. Chem. Soc. 1985, 107, 2192.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);(Registry Number)CH3CH2CON(CH3)2
CH3CON(CH3)2(H3C)2NCO(CH2)6CH=CH2
ether (60-29-7)
Cyclohexene (110-83-8)
carbon tetrachloride (56-23-5)
1,2-dichloroethane (107-06-2)
pyridine (110-86-1)
potassium hydroxide (1310-58-3)
dichloromethane (75-09-2)
styrene (100-42-5)
magnesium sulfate (7487-88-9)
2,4,6-collidine (108-75-8)
triethylamine (121-44-8)
argon (7440-37-1)
calcium hydride (7789-78-8)
α-methylstyrene (98-83-9)
Cyclobutanone (1191-95-3)
N,N-dimethylacetamide (127-19-5)
1-octene (111-66-0)
Trifluoromethanesulfonic anhydride (358-23-6)
3-Hexylcyclobutanone (138173-74-7)
Allyl ethyl ether (557-31-3)
2,6-di-t-butyl-4-methylpyridine (38222-83-2)
Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved