Carbon Suboxide

O=C=C=C=O

[504-64-3]  · C3O2  · Carbon Suboxide  · (MW 68.03)

(1,3-dielectrophile used mainly for the synthesis of five- and six-membered heterocycles functionalized with oxo and hydroxy groups in the 1,3-position1)

Alternate Name: 1,3-dioxo-1,2-propadiene.

Physical Data: mp -112.5 °C; bp 6.8 °C; d 1.114 g cm-3 (at 0 °C); 1.135 g cm-3 (at -12 °C); hD 1.45384.

Solubility: sol ether, THF, benzene, etc.; reacts with H2O and protic solvents.

Preparative Methods: for synthetic use, C3O2 can be prepared conveniently by three routes. (a) Pyrolysis of diacetyl tartaric anhydride at 770 °C under normal pressure.1c (b) Dehydration of malonic acid with P4O10 at 150 °C.1c,2 (c) Thermolysis of bis(trimethylsilyl) malonate in the presence of P4O10 at 160 °C.3 Good results4 are also obtained by using method (b) and the apparatus as depicted in Birkofer and Sommer3 (but also including a calcium oxide tube1c to absorb the acetic acid which is also formed by this most simple procedure). All three procedures can be adjusted to yield at least 7 g (>0.1 mol) of C3O2.

Handling, Storage, and Precautions: pure C3O2 is rather stable;1b nevertheless, it is advisable to use it within a few days after its preparation. Usually solutions of C3O2 in ether or THF are used in synthesis. An assay of the content of such solutions can be performed by adding an excess of aniline to an aliquot, and weighing the amount of malonic acid dianilide formed. Caution: Small amounts of C3O2 act as a lachrymator; in high concentrations it attacks eyes, nose, and respiratory organs, producing a feeling of suffocation. Use in a fume hood.

Reactions.

As an internal dianhydride, C3O2 represents the most electrophilic malonic acid derivative, but due to its value it is only used if other reagents fail. One typical example is the reaction of pyrazoles to yield cross-conjugated mesomeric pyrazolo[1,2-a]pyrazole betaines (eq 1).5

In a similar way amidine derivatives react with C3O2 to yield six-membered pyrimidine betaines (eq 2),2,6 and N-substituted 2-aminopyridines7,8 and pyrimidines9 lead to bicyclic cross-conjugated betaines. 1,3-Dinucleophiles bearing only one hydrogen atom add C3O2 inevitably to zwitterionic compounds.8

Another example is the synthesis of 4-hydroxy-2-pyrones (1), structural units found in many natural products. Silyl enol ether derivatives of aldehydes and ketones react smoothly with C3O2 to afford the trimethylsilyl ether of the target compounds, which are easily hydrolyzed to (1) (eq 3).10 Ketones themselves react very sluggishly with C3O2 even if catalyzed by Lewis acids, and then they afford the pyronopyrones (2) in low yield by reaction of a second equivalent of C3O2 with (1) (eq 4).11 The reason is that ketones are less nucleophilic than 4-hydroxy-2-pyrones. Thus acetone yields (2) (R1 = H, R2 = Me) in only 8% yield,12 whereas triacetic acid lactone (1) (R1 = H, R2 = Me) affords the same compound (2) in 20% yield. The addition of 2 equiv of C3O2 to a substrate, leading to pyrono derivatives of the expected compound, is frequently observed in carbon suboxide reactions.1

Alternatives.

Malonyl Chloride, Bis(2,4,6-trichlorophenyl) Malonate, and even Diethyl Malonate may be used as substitutes. The reaction of trimethylsilyl enol ethers with malonyl dichloride (eq 3) may serve as an example since 4-hydroxy-2-pyrones are also formed with this reagent;13 however, the yield is much lower and side products are formed. It has been shown that N-substituted 2-amino heterocycles form zwitterionic bicyclic pyrimido derivatives (eq 2) in good yields if heated with bis(2,4,6-trichlorophenyl) malonate (AME) to 160 °C for 3 minutes.14 Heating of 2-phenylaminopyridine with diethyl malonate in tetralin forms the expected pyridopyrimidine betaine (eq 2) in 25% yield.15

Related Reagents.

Bis(2,4,6-trichlorophenyl) Malonate; Bis(trimethylsilyl) Malonate; (Chlorocarbonyl)ethylketene; Diethyl Malonate; Malonic Acid; Malonyl Chloride.


1. Reviews: (a) Kappe, T. MOC 1993, E15/2, 3119 (b) Kappe, T.; Ziegler, E. AG(E) 1974, 13, 491. (c) Borrmann, D. MOC 1968; VII/4 286.
2. Potts, K. T.; Sorm, M. JOC 1972, 37, 1422.
3. Birkofer, L.; Sommer, P. CB 1976, 109, 1701.
4. Potts, K. T., personal communication, and the author's own experience.
5. Potts, K. T.; Murphy, P. M.; Kuehnling, W. R. JOC 1988, 53, 2889.
6. Ziegler, E.; Steiger, W.; Strangas, C. ZN(B) 1977, 32b, 1204.
7. Potts, K. T.; Sorm, M. JOC 1971, 36, 8; Kappe, T.; Lube, W. M 1971, 102, 781.
8. Review: Friedrichsen, W.; Kappe, T.; Böttcher, A. H 1982, 19, 1083.
9. Potts, K. T.; Hsia, R. K. C. JOC 1973, 38, 3485.
10. Bonsignore, L; Cabiddu, S.; Loy, G.; Secci, D. H 1989, 29, 913.
11. Hradetzky, F.; Ziegler, E. M 1966, 97, 398; Chirazi, A. M.; Kappe T.; Ziegler, E. AP 1976, 309, 558.
12. Omori, A.; Sonoda, N.; Tsutsumi, S. JOC 1969, 34, 2480; Omori, A.; Sonoda, N.; Uchida, Y.; Tsutsumi, S. BCJ 1969, 42, 3233.
13. Effenberger, F.; Ziegler, T.; Schönwälder, K.-H.; Kesmarsky, T.; Bauer, B. CB 1986, 119, 3394.
14. Coburn, R. A.; Glennon, R. A. JHC 1973, 10, 487.
15. Roschger, P. Ph.D Thesis, University of Graz, Austria, 1990, pp 11, 28.

Thomas Kappe

Karl-Franzens-University of Graz, Austria



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