Diethyl Oxalate

(1; R = Et)

[95-92-1]  · C6H10O4  · Diethyl Oxalate  · (MW 146.14) (2; R = Me)

[553-90-2]  · C4H6O4  · Dimethyl Oxalate  · (MW 118.09) (3; R = Pr)

[615-98-5]  · C8H14O4  · Dipropyl Oxalate  · (MW 174.20) (4; R = Bu)

[2050-60-4]  · C10H18O4  · Dibutyl Oxalate  · (MW 202.25) (5; R = t-Bu)

[691-64-5]  · C10H18O4  · Di-t-butyl Oxalate  · (MW 202.25) (6; R = CH2CH2Cl)

[7208-92-6]  · C6H8Cl2O4  · Bis(2-chloroethyl) Oxalate  · (MW 215.03) (7; R = CH2CH=CH2)

[615-99-6]  · C8H10O4  · Diallyl Oxalate  · (MW 170.16) (8; R = CH2C&tbond;CH)

[71573-77-8]  · C8H6O4  · Di-2-propynyl Oxalate  · (MW 166.13) (9; R = CH2Ph)

[7579-36-4]  · C16H14O4  · Dibenzyl Oxalate  · (MW 270.28)

(one- or two-carbon electrophile in acylation,1,2 two-carbon electrophile for heterocycle synthesis;3 activating group for a-keto ester preparation;4 activating group for regioselective alkylation;5 activating group for diazo ketone preparation6)

Physical Data: (1): mp -40 °C; bp 185 °C; d 1.077 g cm-3. (2): mp 53.3 °C; bp 164 °C. (3): mp -44 °C; bp 212-217 °C; d 1.019 g cm-3. (4): mp -30 °C; bp 242 °C; d 0.987 g cm-3. (5): mp 71 °C. (6): mp 39-40 °C. (7): bp 215 °C; d 1.158 g cm-3. (8): mp 97-98 °C. (9): mp 80 °C.

Solubility: completely sol ether, alcohol and acetone; slightly sol hot water. The solubility of dimethyl oxalate is similar, except that it is more soluble in water. The solubilities of the other esters are similar in organic solvents, but they are insoluble in water.

Form Supplied in: the diethyl and dimethyl esters are readily available commercially in ca. 98% purity.

Preparative Methods: dimethyl oxalate;7 di-t-butyl oxalate;8 others.9

Handling, Storage, and Precautions: diethyl oxalate is harmful if swallowed and is irritating to the eyes. Care should be taken not to inhale the vapor. It is sensitive to moisture. It should be disposed of by burning in an approved incinerator. Dimethyl oxalate has similar properties to the diethyl ester and is harmful by inhalation and through skin. It should be disposed of by burning in an approved incinerator. Little is known about the other esters, which have been much less used. These reagents should be handled in a fume hood.

Esters of Oxalic Acid.

The diethyl ester has been most commonly used in synthesis, but the methyl ester would appear to serve equally well. Other esters may have specific applications.10

Electrophile in Acylation Reactions.

Ketone enolates add to one ester group of diethyl oxalate with the loss of ethanol to give the a,g-diketo ester. The diketo ester can be converted to the b-keto ester by pyrolytic loss of CO. Both steps are exemplified in the synthesis of pimelic acid (eq 1).11 The a,g-diketo ester is enantiotopically reduced by Baker's Yeast to give a diastereomeric mixture of a-hydroxy-g-keto esters which on Clemmensen reduction gives the a-hydroxy ester as a single enantiomer (eq 1).12 Proteus vulgaris reduces a-keto acids to the corresponding (R)-a-hydroxy acids.13

Diethyl oxalate acylates diethyl succinate in the presence of Sodium Ethoxide, and the resulting triester can be hydrolyzed to a-ketoglutaric acid with the loss of CO2 (eq 2).14

Dimethyl oxalate acylates 3-substituted dimethyl glutarates in the presence of Sodium Methoxide to give substituted cyclopentadienes (eq 3).15 a,b-Unsaturated esters are acylated in the same way to give dimers. These are in equilibrium with the corresponding monomer and react with dimethyl malonate under basic conditions to give hydroxycyclopentenones (eq 4).16

Organometallic reagents react with diethyl oxalate in THF to give a-keto esters,17-19 usually in high yield (eq 5). The reaction was successful with a lithiated indole derivative (eq 6).20

Rambaud and co-workers obtained a range of b,g-unsaturated a-keto esters by modification of this method (eq 7).10,13

Benzyl chromium tricarbonyl complexes can be acylated with diethyl oxalate in the presence of Potassium t-Butoxide and the resulting potassium enolate can be hydrolyzed with water or trapped with t-Butyldimethylchlorosilane (eq 8).21

Preparation of Heterocycles.

Urea condenses with diethyl oxalate in the presence of sodium methoxide to give, after neutralization, parabanic acid (eq 9).3

o-Nitrotoluene adds to diethyl oxalate in the presence of potassium ethoxide to give the enolate which on hydrogenation gives ethyl 2-indoylcarboxylate (eq 10).22

When the formimidate group is available to the enolate at the adacent ortho position, then a 4-nitroindole is obtained (eq 11).23

Naphthalene-1,8-diamine reacts on heating with diethyl oxalate to give a pyrimidine derivative (eq 12).24

Activating Group in the Preparation of a,b-Unsaturated Ketones.

Ksander and McMurry4 developed a sequence in which a methyl ketone is acylated by diethyl oxalate and the resulting a,g-diketo ester acts as a nucleophile on treatment with an aldehyde. The resulting diketo lactone is pyrolyzed with the loss of CO and CO2 to give the a,b-unsaturated ketone (eq 13).

Activating Group for Regiospecific Alkylation.

An enol ester has been introduced as a directing group for alkylations, particularly in steroids, by acylation with diethyl oxalate. Methylation can be directed to C-2 rather than C-4 by this procedure, and the directing group is readily removed (eq 14).5,25,26

Activating Group for the Preparation of Diazo Ketones.

Acylation of a methyl ketone with diethyl oxalate in the presence of sodium ethoxide gives the sodium enolate which on treatment with p-Toluenesulfonyl Azide gives the corresponding diazomethyl ketone (eq 15).6

Related Reagents.

Carbon Dioxide; Diethyl Carbonate; Methyl Magnesium Carbonate; Methyl Chlorooxalate; Methyl Cyanoformate; Oxalic Acid; Oxalyl Chloride.

1. Hauser, C. R.; Swamer, F. W.; Adams, J. T. OR 1954, 8, 84.
2. Davis, B. R.; Garratt, P. J. COS 1991, 2, 838.
3. Murray, J. I. OSC 1963, 4, 744.
4. Ksander, G. M.; McMurry, J. E. TL 1976, 4691.
5. Mazur, Y.; Sondheimer, F. JACS 1958, 80, 5220.
6. Harmon, R. E.; Sood, V. K.; Gupta, S. K. S 1974, 577.
7. Bowden, E. OSC 1943, 2, 414.
8. Backer, H. J.; Homan, J. D. H. RTC 1939, 58, 1048.
9. Lespagnol, C. BSF 1960, 110.
10. Rambaud, M.; Bakasse, M.; Duguay, G.; Villieras, J. S 1988, 564.
11. Snyder, H. R.; Brooks, L. A.; Shapiro, S. H. OSC 1943, 2, 531.
12. Tsuboi, S.; Nishiyama, E.; Utaka, M.; Takeda, A. TL 1986, 27, 1915.
13. Schummer, A.; Yu, H.; Simon, H. T 1991, 47, 9019.
14. Bottorff, E. M.; Moore, L. L. OSC 1973, 5, 687.
15. Kojima, K.; Sakai, K. TL 1972, 3337.
16. Brown, R. T.; Blackstock, W. P.; Wingfield, M. TL 1984, 25, 1831.
17. Creary, X. JOC 1987, 52, 5026.
18. Weinstock, L. M.; Currie, R. B.; Lovell, A. V. SC 1981, 11, 943.
19. Middleton, W. J.; Bingham, E. M. JOC 1980, 45, 2883.
20. Bolton, R. E.; Moody, C. J.; Pass, M.; Rees, C. W.; Tojo, G. JCS(P1) 1988, 2491.
21. Le Bihan, J.-Y.; Senechal-Tocquer, M.-C.; Senechal, D.; Gentric, D.; Caro, B.; Halet, J.-F.; Saillard, J.-Y.; Jaouen, G.; Top, S. T 1988, 44, 3565.
22. Noland, W. E.; Baude, F. J. OSC 1973, 5, 567.
23. Bergman, J.; Sand, P. OS 1987, 65, 146.
24. Herbert, J. M.; Woodgate, P. D.; Denny, W. A. JMC 1987, 30, 2081.
25. Ringold, H. J.; Rosenkranz, G. JOC 1956, 21, 1333.
26. Hogg, J. A.; Lincoln, F. H.; Jackson, R. W.; Schneider, W. P. JACS 1955, 77, 6401.

Peter J. Garratt

University College London, UK

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