1-Chloro-3-pentanone

[32830-97-0]  · C5H9ClO  · 1-Chloro-3-pentanone  · (MW 120.58)

(reagent for Robinson annulation; often interchangeable with 1-penten-3-one and the corresponding Mannich base 1-dialkylamino-3-butanone)

Alternate Name: 2-chloroethyl ethyl ketone

Physical Data: bp 62-65 °C/15 mmHg; d 1.042 g cm-3.

Solubility: sol most organic solvents.

Form Supplied in: liquid; commercially available.

Purification: by distillation.

Annulation.

The reagent is the synthetic equivalent of 1-penten-3-one (ethyl vinyl ketone) and the quaternary salt of the Mannich base 1-dimethylamino-3-butanone in the Robinson annulation. The use of the reagent in this annulation has been briefly reviewed.1,2 The reagent is believed to generate the vinyl ketone.3 Although most annulations are done with base in organic solvents, the reagent can also be used with acid in organic4 and in aqueous solution. In water, it reacts as expected with 2-methylcyclopentane-1,3-dione (eq 1).5

However, the corresponding cyclohexane derivative gives an acid as the major product, which presumably results from opening of a bridged aldol intermediate (eq 2).5

Careful examination of products shows that often both mono- and bis-annulation products are formed (eq 3).6 The bis-annulation can give two intermediate products, which converge to one (eq 4).6 The bis-annulation can also be done without isolation of the intermediates (eq 5).7

While most of the annulations have been done with a strong base, the reactions with 1,3-dicarbonyl compounds are efficient with Triethylamine in boiling EtOAc (eq 6).8 This method has been applied to synthesis of spiroenediones (eq 7).9

Quinoline Synthesis.10

The reagent was used to prepare a quinoline by a Skraup-type reaction (eq 8). Although the yield is low, it is comparable to the yields from the a,b-unsaturated aldehydes or ketones, which usually are in the 20-30% range.11


1. Fieser, M.; Fieser, L. F. FF 1972, 3, 49.
2. Fieser, M.; Fieser, L. F. FF 1977, 6, 110.
3. Jung, M. E. T 1976, 32, 3.
4. Zoretic, P. A.; Branchaud, B.; Maestrone, T. TL 1975, 527.
5. Zoretic, P. A.; Bendiksen, B.; Branchaud, B. JOC 1976, 41, 3767.
6. Heathcock, C. H.; Mahaim, C.; Schlecht, M. F.; Utawanit, T. JOC 1984, 49, 3264.
7. Kerwin, S. M.; Paul, A. G.; Heathcock, C. H. JOC 1987, 52, 1686.
8. Uma, R.; Rajagopalan, K.; Swaminathan, S. T 1986, 42, 2757.
9. Ravikumar, V. T.; Sathyamoorthi, G.; Rajagopalan, K.; Swaminathan, S. IJC(B) 1987, 26, 255.
10. Carroll, F. I.; Berrang, B.; Linn, C. P. JMC 1985, 28, 1564.
11. LaMontagne, M. P.; Markovac, A.; Khan, M. S. JMC 1982, 25, 964.

Girts Kaugars

The Upjohn Company, Kalamazoo, MI, USA



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