Glyoxal

[107-22-2]  · C2H2O2  · Glyoxal  · (MW 58.04)

(undergoes condensations and Wittig reactions to form carbo- and heterocycles)

Alternate Name: ethanedial.

Physical Data: yellow prisms, mp 15 °C; bp 50.4 °C/760 mmHg; d204 1.29 g cm-3.

Solubility: sol water, ether, ethanol.

Form Supplied in: crystalline trimeric dihydrate (OHC-CHO)3.2H2O [4405-13-4], which is nonhygroscopic; also supplied as a 40% aqueous solution which may contain polymerization inhibitors. An addition compound with NaHSO3 serves as a nonaqueous form of glyoxal (monohydrate; [517-21-5]).

Purification: for most reactions, can be used without further purification. Anhydrous form should be freshly prepared.1

Handling, Storage, and Precautions: should be handled carefully to avoid exposure. Use in a fume hood.

Condensations.

Glyoxal (1) undergoes the Weiss-Cook reaction with dimethyl 1,3-acetonedicarboxylate in aqueous buffer at pH 8.3 and affords tetramethyl cis-bicyclo[3.3.0]octane-3,7-dione-2,4,6,8-tetracarboxylate (eq 1).2 It undergoes a condensation reaction in methanol in the presence of Formic Acid with Formaldehyde and benzylamine in a stoichiometric ratio 1:2:4 and provides 2,4,6,8-tetrabenzyl-2,4,6,8-tetraazabicyclo[3.3.0]octane (eq 2).3 Condensation of (1) with N,N-diisopropylurea in aqueous HCl at rt affords 2,4,6,8-tetraisopropyl-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione (eq 3).4

Glyoxal reacts with the (2,5)furano-4,4-bis-(2-oxo-3-butyl) sulfide shown in eq 4 upon gradual addition of Sodium Methoxide in methanol to form 1,11-dioxo[3.3](2,5)furano(2,5)thiophenophane (eq 4).5 Reaction of glyoxal with the nickel(II) complex of 1,5,8,12-tetraazadodecane followed by reduction with Sodium Borohydride and treatment with excess Sodium Cyanide affords 1,4,8,11-tetraazacyclotetradecane (cyclam) (eq 5),6 a synthetically useful crown ether analog.

Condensation of glyoxal bisulfite with o-phenylenediamine in aqueous solution at 80 °C affords quinoxaline (eq 6).7 Glyoxal also undergoes cyclocondensation upon heating with 3,4-diamino-1,2,5-thiadiazole and forms [1,2,5]thiadiazolo[3,4-b]pyrazine (eq 7).8

Wittig-Related Reactions.

Freshly prepared (dried) glyoxal,1 when treated with phenacyltriphenylphosphorane, undergoes a Wittig condensation to form both the (E,E)- and (E,Z)-1,4-dibenzoyl-1,3-butadienes (eq 8).9 A similar reaction of (1) with a bis-ylide [generated from 1,8-bis(bromomethyl)biphenylenetriphenylphosphonium salt and dimsylsodium] affords a complex mixture which contains 12% of the interesting cycloocta[def]biphenylene (eq 9).10

Aqueous glyoxal undergoes a Wittig-type condensation with the phosphorane generated from 1,3,4,6-tetrathiapentalene-2-(triphenylphosphonium) trifluoromethanesulfonate and triethylamine to form the mono-Wittig product 1,3,4,6-tetrathiapentalen-2-ylideneacetaldehyde (eq 10).11 A similar reaction of (1) with another phosphorane, derived by treating (4,5-dimethoxycarbonyl-1,3-diselenolyl)tributylphosphonium tetrafluoroborate with triethylamine in THF, affords 2-formylmethylene-4,5-dimethoxycarbonyl-1,3-diselenole (eq 11).12

Glyoxal undergoes formic acid-catalyzed condensations with (R)-PhCHMeNH2 or with (1S,2S,3S,5R)-3-(aminomethyl)pinane, individually, to form the corresponding diazadienes represented by eq 12.13 Reaction of glyoxal with a dicarboxamide (see eq 13) in the presence of the phase-transfer catalyst benzyltributylammonium hydroxide, in H2O/CHCl3 containing sodium hydroxide, affords the bicyclic compound shown.14

Powdered polymeric or monomeric glyoxal in dry benzene reacts with an ethereal solution of phenoxymagnesium bromide upon heating and directly produces the 2-hydroxyphenacyl alcohol (eq 14).15 Reaction of glyoxal (obtained by concentration of 40% glyoxal) with gaseous HBr in methanol and dichloromethane at 0 °C affords 1,2-dimethoxy-1,2-dibromomethane which, upon treatment with sodium t-butoxide, undergoes dehydrobromination to yield 1,2-dimethoxyvinyl bromide (eq 15).16

Reaction of glyoxal with 2-t-butyl-4-methylphenol in refluxing acetic acid in the presence of Hydrogen Chloride or p-Toluenesulfonic Acid as a catalyst affords 5-methyl-7-t-butyl-2(3H)-benzofuranone (eq 16).17 Condensation of (1) with N-aryl substituted ureas produces the corresponding 1-aryl substituted hydantoins (eq 17).18

Glyoxal reacts with chiral N-homoallyl-b-amino alcohols in water-THF solution to produce an iminium ion which undergoes cyclization with complete stereoselectivity and affords the bi- and tricyclic alcohols19 represented in eqs 18 and 19, respectively.

Related Reagents.

For uses of other dialdehydes in synthesis, see Malondialdehyde and Succindialdehyde.


1. Harries, C.; Temme, F. CB 1904, 40, 165.
2. Gupta, A. K.; Fu, X.; Snyder, J. P.; Cook, J. M. T 1991, 47, 3665.
3. Nielsen, A. T.; Nissan, R. A.; Chafin, A. P.; Gilardi, R. D.; George, C. F. JOC 1992, 57, 6756.
4. Koppes, W. M.; Chaykovsky, M.; Adolph, H. G.; Gilardi, R.; George, C. JOC 1987, 52, 1113.
5. Miyahara, Y.; Inazu, T.; Yoshino, T. CL 1980, 397.
6. (a) Barefield, E. K. IC 1972, 11, 2273. (b) Barefield, E. K.; Wagner, F.; Hodges, K. D. IC 1976, 15, 1370.
7. Jones, R. G.; McLaughlin, K. C. OSC 1963, 4, 824.
8. Komin, A. P.; Carmack, M. JHC 1976, 13, 13.
9. Perlmutter, H. D.; Trattner, R. B. JOC 1978, 43, 2056.
10. Wilcox, Jr., C. F.; Uetrecht, J. P.; Grohman, K. K. JACS 1972, 94, 2532.
11. Hansen, T. K.; Lakshmikantham, M. V.; Cava, M. P.; Becher, J. JCS(P1) 1991, 2873.
12. Yoshida, Z.; Awaji, H.; Sugimoto, T. TL 1984, 25, 4227.
13. Tom-Dieck, H.; Dietrich, J. CB 1984, 117, 694 (CA 1984, 101, 22 602d).
14. Sarmah, C. S.; Kataky, J. C. S. Indian J. Heterocycl. Chem. 1992, 1, 261.
15. Casiraghi, G.; Salerno, G.; Sartori, G. S 1975, 186.
16. Skold, C. N. SC 1976, 6, 119.
17. Layer, R. W. JHC 1975, 12, 1067.
18. Nematollahi, J.; Mehta, Z.; Langston, J. JPS 1973, 62, 340.
19. Agami, C.; Couty, F.; Poursoulis, M.; Vaissermann, J. TL 1992, 48, 431.

M. Sreenivasa Reddy & James M. Cook

University of Wisconsin-Milwaukee, WI, USA



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