4-Chloro-2-butanone

[6322-49-2]  · C4H7ClO  · 4-Chloro-2-butanone  · (MW 106.55)

(reagent for Robinson annulation; often interchangeable with methyl vinyl ketone and the corresponding Mannich base 4-dialkylamino-2-butanone)

Alternate Names: 2-chloroethyl methyl ketone; 1-chloro-3-butanone.

Physical Data: bp 105-110 °C.

Solubility: sol most organic solvents.

Analysis of Reagent Purity: 1H NMR data are available.1

Form Supplied in: liquid; commercially available.

Purification: by distillation.

Handling, Storage, and Precautions: use in a fume hood.

Annulation.

4-Chloro-2-butanone is one of three reagents commonly used for unsubstituted ring formation in the Robinson annulation. The other reagents are 3-buten-2-one (Methyl Vinyl Ketone, MVK) and the quarternary salt of the Mannich base 4-dimethylamino-2-butanone (or 4-diethylamino-2-butanone). The choice of reagent for the best yield from a specific substrate has to be determined empirically. MVK is the most difficult to handle because it can polymerize during preparation or annulation. Nevertheless, MVK has been widely used.2

One of the first annulations3 with 4-chloro-2-butanone gave the product in a 70% yield, whereas only 12% was obtained from the corresponding Mannich base (eq 1). The acid-catalyzed annulation, first developed with 1-chloro-3-pentanone,4,5 has been used with 4-chloro-2-butanone6 to afford a much better yield (eq 2) than was obtained with MVK (12-34%).

Annulation by Dialkylation.

The dimethylhydrazone of a cyclic 1,3-dione reacts regioselectively to give the dialkylated hydrazone, which can then be cyclized sequentially to the bicyclic and the tricyclic ketones (eq 3).7 The reaction works equally well for 1,3-cyclohexanedione and 1,3-cyclopentanedione.

Stannylation.

The reagent reacts with Tin(II) Chloride to form the b-trichlorostannyl ketone, which can also be prepared (slightly faster) from HSnCl3 and MVK as well as other vinyl ketones. The intermediate trichloro compounds can be converted to the tributylstannyl ketones (eq 4).8

Alkynylsilane Functionalization.

Organometallic derivatives of propargylic silanes react with the reagent, as well as other a- or o-chlorocarbonyl compounds, to form homopropargylic alcohols (with the Zn reagent, eq 5)9 or allenic alcohols (with the Al reagent, eq 6).10 The products are used to form oxygenated heterocycles.11


1. Just, G.; Crosilla, D. CJC 1980, 58, 2349.
2. Jung, M. E. T 1976, 32, 3.
3. Howell, F. H.; Taylor, D. A. H. JCS 1958, 1248.
4. Zoretic, P. A.; Branchaud, B.; Maestrone, T. TL 1975, 527.
5. Heathcock, C. H.; Mahaim, C.; Schlecht, M. F.; Utawanit, T. JOC 1984, 49, 3264.
6. Paquette, L. A.; Belmont, D. T.; Hsu, Y.-L. JOC 1985, 50, 4667.
7. Demir, A. S.; Enders, D. ZN(B) 1989, 44, 834.
8. Nakahira, H.; Ryu, I.; Ogawa, A.; Kambe, N.; Sonoda, N. OM 1990, 9, 277.
9. Mesnard, D.; Miginiac, L. JOM 1990, 397, 127.
10. Mesnard, D.; Miginiac, L. JOM 1991, 403, 299.
11. Mesnard, D.; Miginiac, L. JOM 1990, 397, 139.

Girts Kaugars

The Upjohn Company, Kalamazoo, MI, USA



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