Science of Synthesis

Olpp, T., Science of Synthesis, (2007) 25, 424.

The oxidation of C—H bonds α to carbonyl groups by selenium dioxide is an established method for the generation of 1,2-diketones.[‌18‌–‌21‌] 2-Oxoaldehydes are accessible by this method if the α-position is either a methyl group (e.g., ‌7‌) or the carbonyl group is an aldehyde (e.g., ‌9‌) (‌Scheme 3‌). For a high-yielding process the substituent R1 must be inert, i.e. should possess ideally no C—H bond in the α-position of the ketone (arenes, hetarenes, and quaternary carbon atoms). If an activated C—H bond is present in the product ‌8‌ (e.g., in methylglyoxal, R1 = Me) the starting material should be used in (large) excess to avoid further oxidation of the product. An excess of selenium dioxide, however, is reported to cause overoxidation to glyoxylic acids.[‌14‌] In the presence of water the reaction is accelerated due to the higher reactivity of selenous acid (H2SeO3) formed from selenium dioxide and water.[‌21‌] This method is generally applicable for the synthesis of aryl and hetaryl glyoxals and even bisglyoxals[‌22‌,‌23‌] have been prepared. However, a limitation is that some nitrogen-containing aryl methyl ketones cannot be oxidized to the corresponding glyoxals: 2-acetamidoacetophenone[‌24‌] and 2-acetylpyridine[‌25‌] are oxidized to glyoxylic acids. This corresponds to the observation that non-nitrogen containing aryl methyl ketones are oxidized to glyoxylic acids by selenium dioxide in the presence of pyridine.[‌26‌] A solid-phase reaction including microwave heating of the reactants on silica gel represents a simple experimental alternative.[‌27‌] A variation using catalytic amounts of a selenium oxidant (diphenyl diselenide) and a stoichiometric quantity of ammonium peroxydisulfate [(NH4)2S2O8] in methanol delivers protected glyoxals directly, namely dimethyl 2-oxoacetals.[‌28‌] As an alternative to selenium dioxide as oxidant, ammonium chlorochromate (NH4CrO3Cl) in dimethylformamide is reported to convert acetophenone (‌7‌, R1 = Ph) and phenylacetaldehyde (‌9‌, R1 = Ph) into phenylglyoxal (‌8‌, R1 = Ph) in 80 and 87% yields, respectively.[‌29‌,‌30‌]

‌Meeeee 8‌ Meeeeeeee ee Meeeee Meeeeee eee Meeeeeeee[‌8‌,‌88‌,‌88‌,‌88‌,‌88‌,‌88‌–‌88‌]

‌Meeeeeeeeee 8‌

M8	Meeeeeee Meeeeeee	MeM8 (eeeee)	Meeeeeeeee	Meeee (%)	Mee
M	‌8‌	–e	88°M, eeeeeeeee, 8 e	88e,e	[‌88‌]
Me	‌8‌	–e	eeeeee, 8–8 e	88e,e,e	[‌88‌]
Me	‌8‌	–e	eeeeee, 8 e	88e,e	[‌88‌]
Me	‌8‌	8.8	8,8-eeeeeee/M8M (88:8), eeeeee, 88 e	88e,e	[‌88‌]
Me	‌8‌	–e	eeeeee, 8 e	88e	[‌88‌]
8-M8MM8M8	‌8‌	8.8	8,8-eeeeeee/M8M (88:8), eeeeee, 8 e	88e	[‌88‌]
M8M8	‌8‌	8.8	8,8-eeeeeee/M8M (88:8), 88–88°M, 8 e	88e	[‌88‌]
e-Me	‌8‌	8.8	MeMM/M8M (88:8), eeeeee, 8 e	88e,e	[‌8‌]
	‌8‌	8.8	MeMM/M8M (88:8), 88°M, 88 e	88e	[‌88‌]
	‌8‌	8.8	MeMM/M8M (8:8), 88°M, 8 e	88e,e	[‌88‌]
	‌8‌	8.8	8,8-eeeeeee/M8M (88:8), 88°M, 8 e	88e,e	[‌88‌]
	‌8‌	8.8	8,8-eeeeeee/M8M (88:8), eeeeee, 88 e	88e	[‌88‌]
	‌8‌	8.8	8,8-eeeeeee, eeeeee, 88 e	88e	[‌88‌]

e Meeeeeeee ee eeee ee e eeeee eeeeee ee eeeeeee, eee eeeee ee eeeee ee MeM8.

e Meeeeeee ee eeeeeeeeeee.

e Meeee eeeeeee ee eeee.

e Meeeeeee ee eeeee eeee.

e Meeeeeee ee eeeeeeeeeee eeeee eeeeeeeee (eeeeeeeeeeeeeee) eeee eeeee.

e Meeeeeee ee eeeeeeeeeee eeeee eeeeeeeee (eeeeeeeeeeeeeee) eeee eeeee.

Meeeeeeeeeee Meeeeeeee

Meeeeeeeeeeee (‌8‌, M8 = Me) eee Mee Meeeeeeeeee; Meeeeee Meeeeeeee:[‌88‌,‌88‌]

MMMMMMM: Meeeeeee eeeeeee ee eeeeee eeeee. Me eee ee eeeee ee eeeeeeeeee, eeeeeeeee, ee eeeeeee eeee eeee ee eeeeee eeeeeeeee. Me ee e eeeeeeee eeeeeee eee eee eeeeee eee MMM. Meeeeeee eeeeeeeeee eeeeeeee eeeeee ee eeeee eeeeee eeeeeeee eee eeeeeeee.

MeM8 (88 e, 8.88 eee) eee eeeee ee e eeeeeee ee M8M (88 eM) eee 8,8-eeeeeee (888 eM) eee eeeeeee ee 88–88°M. Meee eeeeee eee MeM8 eee eeee eeee eeee, MeMMMe (‌8‌, M8 = Me; 88 e, 8.8 eee) eee eeeee ee eee eeeeeee. Meeee eeeeeeeee eee 88 e, eee eeee eee eeeeeeee eee ee eeeeee eeeeeeeee Me eee eee eeeeee-eeeeee eeeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeeeee eeeeeee-eeeeee eee eee eeeeeee eeee MMMe8 (888 eM) eee eeeeee eeeeeee eeee eee. MeMMM8 (888 eM) eee M8M (888 eM). Meeee eeeeee (MeMM8), eee eeeeeeeeeee eeeeee eeeeee eeee eeee eee eeeeeee ee eeeeeeeeee eeeeeee Meeeee. Mee eeeeee eeee eeeeee eeeeeee-eeeeee eee ee eeeeeeeee ee eeeeeeeee eee Me. Meeee eeeeeeeeeee ee eee eeeeeeee, eee eeeeeeeee eee eee eeeeeeee ee eeeeeeeeeeee eeeee eeeeeee eeeeeeee (88–88°M/88 Meee) eee MeMMMMM (‌8‌, M8 = Me) eee eeeeeeee ee eeeeee eee; eeeee: 88 e (88%). Meeeeeeeeeeee MM8Me8 eeeee ee eeee eee eeeeeeee ee eee eeeeeeee eee eee eeeee eeeeeee eeeee eeee ee eeeeeeee ee eeeeeeeeeeeeee.[‌88‌] MeMMMMM (‌8‌, M8 = Me) eee eeeeeeeee eeee eee eeeeeeeeeee ee eeeeeeeee ee M8M (888 eM). Meeee 8 e, eeeeeeee eee eeeee eee eee eeee eee eeeeeeee. Mee eeeeeeeeeee eeeeee ee eeeeeeee eeeeeeeee ee 8°M eee eeeeeeee, eeeeee eeee eee eeeee, eee eeeee. Meee eeee eee eeeeeeeeeee (eee eeeeeeee ‌8‌, ‌Meeeee 8‌) (M8 = Me); eeeee: 88 e (88%).

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 8/8, 888.
• 8.Meeeee-Meee, (8888) 8/8e, 888.
• 8.Meeeee-Meee, (8888) M 8, 888.