Malonyl Chloride

[1663-67-8]  · C3H2Cl2O2  · Malonyl Chloride  · (MW 140.95)

(reactive acyl chloride/C3O2 equivalent;1 self condensation;2 reacts with various functional groups to give heterocyclic compounds3)

Physical Data: colorless liquid, bp 58 °C/26 mmHg; d 1.4486 g cm-3.

Solubility: sol most organic solvents; reacts violently with H2O and protic solvents.

Form Supplied in: colorless or red liquid; widely available in differing purity.

Preparative Methods: from Malonic Acid and Thionyl Chloride.4

Handling, Storage, and Precautions: unstable at rt and should be used freshly distilled in vacuo or freshly prepared; however, it can be stored in the cold for several days; lachrymatory; use in a fume hood.

Acylation.

Malonyl chloride may be used as other acyl halides in Friedel-Crafts and related reactions.5 Thus cyclic hydrocarbons may be prepared by a [3 + n] annulation from aromatic compounds (eq 1) and organometallics (eq 2). Similarly, malonyl chloride can be used like other a,o-carboxylic acid derivatives for the synthesis of macrocycles.6 In this respect, malonyl chloride behaves identically to C3O2 (see Carbon Suboxide), although its reactivity is significantly lower.1,7

Preparation of Heterocycles.

Compounds possessing two nucleophilic centers yield heterocycles upon treatment with malonyl chloride. The reaction proceeds via initial HCl elimination from malonyl chloride8 to give chlorocarbonyl ketenes (1) which are stable for the substituted counterparts (see (Chlorocarbonyl)ethylketene). This elimination is even induced by weak bases such as acetone.2,8 The ketene intermediate may then react with the respective nucleophile or it dimerizes in the case of malonyl chloride in a [4 + 2] fashion to yield 6-chloro-3-chlorocarbonyl-4-hydroxy-2-oxo-2H-pyran (2) (eq 3).2

With enolizable ketones and b-dicarbonyl compounds, pyrones are normally obtained via ketene (1). Unsymmetrically substituted diketones give, however, mixtures of isomers.9 Furthermore, some of the pyrones formed can further add malonyl chloride or ketene (1) to give pyrano[4,3-b]pyran-2,5-diones (eq 4).1,10

Of the numerous examples reported so far for the condensation of malonyl chloride with 1,2- and 1,3-heteroatom-containing nucleophiles, most of the products are very similar to those obtained from the respective nucleophile and C3O2, chlorocarbonyl ketene, or active malonates.1 Some newer examples for the use of malonyl chloride include the preparation of barbituric acid derivatives from silylated carbodiimides,11 coumarins from salicylic aldehyde imines,12 pyridones from ketene S,N-acetals,13 diazepines from diamines,14 and pyranopyrans from malonamides.15 Amidines and similar nucleophiles condense with malonyl dichloride, chlorocarbonyl ketene, and C3O2 to give mesoionic heterocycles (betaines).3,16 These are synthetically useful compounds since, for example, highly substituted pyridones can be prepared by a cycloaddition reaction (eq 5). Enol ethers that are derived from aldehydes react at low temperature with malonyl chloride via (1) to give, after workup with ethanol, 1,3,5-tricarbonyl compounds that can be further converted to otherwise difficult to obtain 6-unsubstituted pyrones (eq 6).17

From ketone-derived alkyl and trimethylsilyl enol ethers, mixtures of the corresponding phloroglucinols, cyclophanes, and substituted or methylene-bridged pyrones are produced upon condensation with malonyl chloride (eq 7).18

Less nucleophilic functional groups like nitriles react with malonyl chloride via the intermediate chlorocarbonyl pyrone (2) to give pyrano[3,4-e][1,3]oxazines.19 However, the product distribution depends on the nitrile, the reaction conditions and, if present, on the substituent of the malonyl chloride. Thus oxazinones (eq 8),20 pyridones (eq 9),21 and pyrimidones (eq 10)19 can be obtained as well.

The condensation of nitriles with malonyl chloride has been reviewed.1b Thiocyanates,22 isothiocyanates,23,24 and cyanates24 condense with malonyl chloride in a similar fashion to nitriles via (2) to give 2-substituted 7-chloropyrano[3,4-e][1,3]oxazine-4,5-diones (eq 11). Similarly, cyanamides yield pyrano[4,3-d][1,3]oxazines and pyrano[4,3-b]azetidinones, depending on the reaction conditions (eq 12).

Related Reagents.

Bis(2,4,6-trichlorophenyl) Malonate; Carbon Suboxide; (Chlorocarbonyl)ethylketene.


1. (a) Kappe, T.; Ziegler, E. AG 1974, 86, 529. (b) Kappe, T. MOC 1993, E15/3, 3119.
2. (a) Davis, S. J.; Elvidge, J. A. JCS 1952, 4109. (b) Elvidge, J. A. JCS 1962, 2606.
3. (a) Kappe, T. Wiss. Z. Karl-Marx-Univ. Leipzig, Math.-Naturwiss. R. 1983, 32, 437. (b) Yanagida, S.; Komori, S. S 1973, 189.
4. Raha, C. OS 1953, 33, 20.
5. (a) Fleischer, K.; Retze, E. CB 1922, 55, 3280. (b) Neidlein, R.; Gartner, R. CZ 1980, 104, 304. (c) Degl'Innocenti, A.; Dembech, P.; Mordini, A.; Ricci, A.; Seconi, G. S 1991, 267.
6. (a) Bradshaw, J. S.; Hansen, L. D.; Nielsen, S. F.; Thompson, M. D.; Reeder, R. A.; Izatt, R. M.; Christensen, J. J. CC 1975, 874. (b) Bradshaw, J. S.; Bishop, C. T.; Nielsen, S. F.; Asay, R. E.; Masihdas, D. R. K.; Flanders, E. D.; Hansen, L. D.; Izatt, R. M.; Christensen, J. J. JCS(P1) 1976, 2505. (c) Anchisi, C.; Corda, L.; Fadda, A. M.; Maccioni, A.; Podda, G. JHC 1984, 21, 577. (d) Lemaire, M.; Vriesema, B. K.; Kellog, R. M. TL 1985, 26, 3499.
7. Cabiddu, S.; Bonsignore, L.; Loy, G.; Secci, D. JHC 1991, 28, 553.
8. (a) Ziegler, E.; Sterk, H. M 1967, 98, 1104. (b) Ziegler, E. C 1970, 24, 62. (c) Ziegler, E.; Sterk, H.; Steiger, W. M 1970, 101, 762.
9. (a) Butt, M. A.; Elvidge, J. A. JCS 1963, 4483. (b) Ziegler, E.; Hradetzky, F. M 1966, 97, 710. (c) Eder, M.; Ziegler, E.; Prewedourakis, E. M 1968, 99, 1395. (d) Ott, W.; Kollenz, G.; Ziegler, E. S 1976, 546.
10. Chirazi, A. M.; Kappe, T.; Ziegler, E. AP 1975, 76, 558.
11. Birkofer, L.; Lückenhaus, W. LA 1984, 1193.
12. Sard, H.; Meltzer, P.; Razdan, R. K. JHC 1985, 22, 257.
13. Chakrasali, R. T.; Ila, H.; Junjappa, H. S 1988, 87.
14. Colombo, A.; Frigola, J.; Pares, J.; Andaluz, B. JHC 1989, 26, 949.
15. Saalfrank, R. W.; Hörner, B. CB 1993, 126, 841.
16. (a) Kappe, T.; Fritz, P. F.; Ziegler, E. M 1971, 102, 412. (b) Ziegler, E.; Steiger, W.; Strangas, C. ZN(B) 1977, 32, 1204. (c) Potts, K. T.; Sorm, M. JOC 1971, 36, 8. (d) Potts, K. T.; Kuehnling, W. R. JOC 1984, 49, 3672. (e) Potts, K. T.; Murphy, P. M.; Kuehnling, W. R. JOC 1988, 53, 2889.
17. (a) Effenberger, F.; Maier, R. Schönwälder, K.-H.; Ziegler, T. B 1982, 115, 2766. (b) Effenberger, F.; Ziegler, T.; Schönwälder, K.-H. B 1985, 118, 741.
18. (a) Effenberger, F.; Schönwälder, K.-H.; Stezowski, J. J. AG 1982, 94, 863. (b) Effenberger, F.; Schönwälder, K.-H. B 1984, 117, 3270. (c) Schönwälder, K.-H.; Kollat, P.; Stezowski, J. J.; Effenberger, F. B 1984, 117, 3280. (d) Effenberger, F.; Ziegler, T.; Schönwälder, K.-H.; Kesmarszky, T.; Bauer, B. B 1986, 119, 3394.
19. (a) Davis, S. J.; Elvidge, J. A. JCS 1962, 3553. (b) Elvidge, J. A.; Zaidi, N. A. JCS(C) 1968, 2188.
20. Ziegler, E.; Kleineberg, G.; Meindl, H. M 1963, 94, 544.
21. (a) Davis, S. J.; Elvidge, J. A.; Foster, A. B. JCS 1962, 3638. (b) Stensrud, T.; Bernatek, E.; Johnsgaard, M. ACS 1971, 25, 523.
22. (a) Al-Rawi, J. M. A.; Elvidge, J. A. JCS(P1) 1973, 2432. (b) Al-Rawi, J. M. A.; Elvidge, J. A. JCS(P1) 1976, 2462. (c) Al-Rawi, J. M. A.; Elvidge, J. A. JCS(P1) 1977, 2536. (d) Ried, W.; Nenninger, J.; Bats, J. W. B 1983, 116, 3725. (e) Ried, W.; Nenninger, J.; Bats, J. W. B 1985, 118, 1371.
23. Al-Rawi, J. M. A.; Mahmood, A.-H. T. JPR 1988, 330, 859.
24. Butt, M. A.; Elvidge, J. A.; Foster, A. B. JCS 1963, 3069.

Thomas Ziegler

University of Stuttgart, Germany



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