2,4-Pentanedione

(keto)

[123-54-6]  · C5H8O2  · 2,4-Pentanedione  · (MW 100.13) (enol)

[1522-20-9]

(carbon-carbon condensations involving mono-, di-, and trianions; formation of pyrazoles, isoxazoles, pyrroles, and pyridines; catalysis by metal chelates)

Alternate Names: acetylacetone; acac.

Physical Data: liquid, bp 45 °C/30 mmHg;26 d 0.975 g cm-3. Keto form: mp -23 °C; bp 134-136 °C.24 Enol form: mp -9 °C.24

Solubility: misc organic solvents; sol dil HCl; slightly sol hot H2O.24

Form Supplied in: commercially available liquid, in which the enol form predominates; the keto form predominates in aq soln.

Preparative Methods: conveniently prepared by BF3-catalyzed reaction of acetone and acetic anhydride, or by reaction of ethyl acetate, acetone, and NaOEt.25

Purification: distillation after drying over anhyd K2CO3; several other methods are available.26

Handling, Storage, and Precautions: moderately toxic; reactions should be conducted in a well-ventilated fume hood.

General Considerations.

2,4-Pentanedione (1) is weakly acidic (pKa &AApprox; 9) and exists as a solvent-dependent tautomeric mixture. The enol form is favored by aprotic organic solvents, being stabilized by internal hydrogen bonding. Reactions of (1) involve (i) reactions of electrophiles at the 3-position via the enolate anion (eq 1), (ii) reactions at the terminal methyl position via the 1,3-dianion (eq 1), (iii) reactions at the terminal position via the 1,3,5-trianion, and (iv) nucleophilic attack on the carbonyl groups, often to form heterocyclic compounds.

Alkylations of monoanions of (1) and homologs can occur on either carbon or oxygen, the site of reaction depending on alkylating agent, counterion, and solvent.1 Dialkylation can be a serious complication. The highly toxic TlI chelates were reported to be effective for alkylation,2 but claims for carbon specificity with alkyl halides other than MeI have been disputed.3 Preferable counterions for C-alkylation include NiII 4 and R4N+.5 Alkylations carried out with K2CO3 in EtOH lead to the corresponding alkylated ketones via retro-Claisen reactions of the alkylated diketone.6 For arylations, SRN1 processes have been observed in a few cases, but the processes are by no means general.7

Other widely used reactions1 involving the monoanions of (1) and homologs include conjugate additions (Michael reactions) to a,b-unsaturated compounds,8 and aldol9 and Knoevenagel10 reactions with carbonyl compounds. The Knoevenagel reactions employ secondary amine catalysts and are likely to involve iminium ion and/or enamine intermediates. Enol esters of (1) are produced by treatment with acid chlorides in pyridine.11

The reagent can be converted to the 1,3-dianion by treatment with alkali amides in liquid ammonia or Lithium Diisopropylamide in THF.12 The dianion undergoes reaction exclusively at the 1-position and is markedly more reactive than the monoanion. Reactions of the dianion include alkylation, arylation by benzyne and radical pathways, aldol condensations, conjugate additions, acylations, and carboxylation.12 Condensations with aliphatic carbonyl compounds subject to ionization are best carried out with dilithio-(1). Dianions of higher aliphatic homologs of (1) form preferentially at the less-branched sites. Acylations of (1) and benzoylacetone by aromatic esters to give 1,3,5-triketones can also be achieved using Sodium Hydride as the ionizing base; the reactions may not involve dianions.13 Other types of electrophiles have given fair to poor results in the NaH system. The strongly basic 1,3,5-trianion has been prepared; only limited studies of its reactivity have been made.14

Heterocycles.

The difunctionality of 2,4-pentanedione has frequently been used in the synthesis of heterocyclic compounds. Examples include reactions to form pyrazoles, isoxazoles, pyrroles, and pyridines.15

Transition Metal Chelates.

Metals form highly crystalline chelated complexes with (1), some of which have useful applications as synthetic reagents. Copper(II) Acetylacetonate modifies the reactivity of carbenes generated from diazo compounds.16 Reactions appear to involve copper-carbene complexes. For example, it stabilizes benzoylcarbene sufficiently to permit 1,3-dipolar additions and catalyzes intramolecular dimerization of 1,7-bis(diazo)-1,6-heptanediones to cyclohept-2-ene-1,4-diones. Tris(acetylacetonato)iron(III) catalyzes reductive decyanation of alkyl nitriles by sodium and epoxidations of alkenes by H2O2 in MeCN.17 Manganese(III) Acetylacetonate oxidizes phenols to dimers without formation of quinones.18 Nickel(II) Acetylacetonate, a cancer suspect agent, is a highly effective catalyst for addition of b-diketones to Michael acceptors; it catalyzes coupling of aryl Grignard reagents with aryl iodides, and in the Wilke catalytic system (Ni(acac)2-PPh3-AlEt3) it alters the regiochemistry of some Diels-Alder reactions between dienes.19,20 The pyridine complex of Palladium(II) Acetylacetonate is a homogeneous catalyst for reduction of nitrobenzene.20,21 Vanadyl Bis(acetylacetonate) catalyzes oxidation by t-Butyl Hydroperoxide of tertiary amines to N-oxides, alkenes to epoxides, and aniline to nitrobenzene.22 Organoboranes require addition of Bis(acetylacetonato)zinc(II) to achieve Pd-catalyzed cross-coupling with aryl and benzyl halides.23 Zr(acac)4 [17501-44-9] catalyzes acylation of amines, thiols, and alcohols (primary > phenol > secondary) by 3-acyl-2-oxazolones.24


1. House, H. O. Modern Synthetic Reactions, 2nd ed.; Benjamin: New York, 1972; Chapter 9.
2. Taylor, E. C.; McKillop, A. ACR 1970, 3, 338.
3. Hooz, J.; Smith, J. JOC 1972, 37, 4200.
4. Boya, M.; Moreno-Manas, M.; Prior, M. TL 1975, 1727.
5. (a) Clark, J. H.; Miller, J. M. JCS(P1) 1977, 1743. (b) Shono, T.; Kashimura, S.; Sawamura, M.; Soejima, T. JOC 1988, 53, 907.
6. Boatman, S.; Hauser, C. R. OSC 1973, 5, 767.
7. (a) Beugelmans, R.; Bois-Choussy, M.; Boudet, B. T 1982, 38, 3479. (b) Scamehorn, R. G.; Hardacre, J. M.; Lukanich, J. M.; Sharpe, L. R. JOC 1984, 49, 4881.
8. Bergmann, E. D.; Ginsburg, D.; Pappo, R. OR 1959, 10, 179.
9. Nielsen, A. T.; Houlihan, W. J. OR 1968, 16, 1.
10. Jones, G. OR 1967, 15, 204.
11. Claisen, L. LA 1896, 291, 25.
12. (a) Harris, T. M.; Harris, C. M. OR 1969, 17, 155. (b) Harris, T. M.; Hay, J. V. JACS 1977, 99, 1631. (c) Hampton, K. G.; Harris, T. M.; Hauser, C. R. OSC 1973, 5, 848. (d) Hampton, K. G.; Harris, T. M.; Hauser, C. R. OSC 1988, 6, 928. (e) Light, R. J.; Hauser, C. R. JOC 1961, 26, 1716. (f) Kirby, F. B.; Harris, T. M.; Hauser, C. R. JOC 1963, 28, 2266. (g) Work, S. D.; Hauser, C. R. JOC 1963, 28, 725. (h) Harris, T. M.; Combs, C. S., Jr. JOC 1968, 33, 2399.
13. Miles, M. L.; Harris, T. M.; Hauser, C. R. JOC 1965, 30, 1007.
14. Hubbard, J. S.; Harris, T. M. JACS 1980, 102, 2110.
15. (a) Wiley, R. H.; Hexner, P. E. OSC 1963, 4, 351. (b) Harries, C.; Haga, T. CB 1899, 32, 1191. (c) Fischer, H. OSC 1955, 3, 513. (d) Eisner, U.; Kuthan, J. CRV 1972, 72, 1.
16. (a) Huisgen, R.; Binsch, G.; Ghosez, L. CB 1964, 97, 2628. (b) Font, J.; Serratosa, F.; Valls, J. CC 1970, 721. (c) Nozaki, H.; Takaya, H.; Moriuti, S.; Noyori, R. T 1968, 24, 3655.
17. (a) van Tamelen, E. E.; Rudler, H.; Bjorklund, C. JACS 1971, 93, 7113. (b) Tohma, M.; Tomita, T.; Kimura, M. TL 1973, 4359.
18. Dewar, M. J. S.; Nakaya, T. JACS 1968, 90, 7134.
19. (a) Nelson, J. H.; Howells, P. N.; DeLullo, G. C.; Landen, G. L.; Henry, R. A. JOC 1980, 45, 1246. (b) Clough, R. L.; Mison, P.; Roberts, J. D. JOC 1976, 41, 2252. (c) Wilke, G. AG(E) 1963, 2, 105. (d) Garratt, P. J.; Wyatt, M. CC 1974, 251.
20. (a) Black, T. H. Aldrichim. Acta 1982, 15, 13. (b) Datta, M. C.; Saha, C. R.; Sen, D. CI(L) 1975, 1057.
21. (a) Sheng, M. N.; Zajacek, J. G. JOC 1968, 33, 588; OSC 1988, 6, 501. (b) Gould, E. S.; Hiatt, R. R.; Irwin, K. C. JACS 1968, 90, 4573. (c) Howe, G. R.; Hiatt, R. R. JOC 1970, 35, 4007.
22. Wakita, Y.; Yasunaga, T.; Akita, M.; Kojima, M. JOM 1986, 301, C17.
23. Kunieda, T.; Mori, T.; Higuchi, T.; Hirobe, M. TL 1985, 26, 1977.
24. Dictionary of Organic Compounds, 5th ed., 6th Suppl.; Buckingham, J., Ed.; Chapman and Hall: New York, 1988; p 353.
25. (a) Denoon, C. E., Jr. OSC 1955, 3, 16. (b) Adkins, H.; Rainey, J. L. OSC 1955, 3, 17.
26. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: New York, 1988; p 70.

Thomas M. Harris

Vanderbilt University, Nashville, TN, USA



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