Science of Synthesis

Joule, J. A., Science of Synthesis Knowledge Updates, (2010) 2, 114.

A Leimgruber–Batcho-type intermediate is almost certainly involved in a sequence (‌Scheme 152‌) which begins with the ready base-catalyzed condensation of an o-nitroaraldehyde ‌459‌ with nitromethane to give a 1-nitro-2-(o-nitroaryl)ethene ‌460‌. Commonly, sodium hydroxide or ammonium acetate/acetic acid are used to promote the condensation; potassium fluoride is also used.[‌398‌] The 1-nitro-2-(o-nitroaryl)ethenes can also be obtained by nitration of 1-aryl-2-nitroethenes.[‌399‌,‌400‌] Reduction, traditionally with metal/acid combinations,[‌399‌–‌402‌] then leads to a 2,3-unsubstituted indole ‌464‌, the simplest interpretation for which being the formation of an intermediate arylamino-enamine ‌461‌ (not isolated) comparable to that involved in the Leimgruber–Batcho sequence. As in that sequence, protonation of ‌461‌ gives ‌462‌, heterocyclic ring closure to ‌463‌ being followed by final loss of ammonia producing the indole ‌464‌. Alternative methods for the reductive cyclization of 1-nitro-2-(o-nitroaryl)ethenes include (see ‌Table 7‌): catalytic transfer hydrogenation,[‌403‌] titanium(III) chloride,[‌404‌] sodium borohydride/palladium/carbon,[‌405‌] hydrogen/palladium(II) hydroxide/carbon,[‌406‌] palladium/carbon/ammonium formate/formic acid,[‌403‌] and iron/acetic acid/silica gel.[‌400‌] In the very special case of the synthesis of the sensitive 1H-indole-5,6-diol, the precursor, 2-(4,5-dihydroxy-2-nitrophenyl)-1-nitroethene was made by nitration of 2-(4,5-dihydroxyphenyl)-1-nitroethene with tetranitromethane in the presence of zinc sulfate, and the reductive ring closure was achieved with sodium dithionite, again in the presence of zinc sulfate.[‌407‌]

‌Meeeee 888‌ Meeeeee eeee 8-Meeee-8-(e-eeeeeeeee)eeeeeee

‌Meeee 8‌ Meeeeee eeee 8-Meeee-8-(e-eeeeeeeee)eeeeeee[‌888‌,‌888‌,‌888‌,‌888‌,‌888‌]

Meeeeeee Meeeeeee	Meeeeeeeee M	Meeeeeeeee MM	Meeeeee	Meeee (%)	Mee
8-[8,8-eee(eeeeeeeee)- eeeeee]-8-eeeeeeeeeee	eeeee MMM8, MeMM	Me, MeMM, eeeeee		88	[‌888‌]
8-eeeeee-8-eeeee- eeeeeeeeeeee	MeMM8, MeMM, MeMM, -88°M eeee Me8M, eeeeee	M8, Me/M, MeMMe, MeMM		88	[‌888‌]
8,8-eeeeeeeee- 8-eeeeeeeeeeeeeeeee	MeMM8, MM8MMe, MeMM, 88°M	M8 (88.8 eee), Me(MM)8/M, MMM, MeMM, 88°M		88	[‌888‌]
8-(8,8-eeeeeeeee- 8-eeeeeeeeeee)- 8-eeeeeeeeeee	–	Me/M, MM8MMM8, MeMM, eeeeee, M8		88	[‌888‌]
8-(8-eeeeeeeee- 8-eeeeeee-8- eeeeeeeeeee)- 8-eeeeeeeeeee	–	Me, MeMM, eeeeee eee, eeeeeee/eeeeeeeeeee (8:8), eeeeee		88	[‌888‌]

Meeeeeeeeeee Meeeeeeee

8,8-Meeeeeeee-8M-eeeeee (‌888‌); Meeeeee Meeeeeeee:[‌888‌]

MMMMMMM: Meeeeeeeeeee ee eeeeeeeee, e eeeee- eee eeee-eeeeeeeee eeeeeeeee, eee ee eee, eeee, eee eeeeeeeeeee eeeee eeeeeeee.

8,8-Meeeeeeee-8-eeeeeeeeeeeeeeeee (88.8 e, 888 eeee) eee eeeeeeeee eeee MeMM8 (88 eM) eeeee MM8MMe (88.8 e, 888 eeee) ee MeMM (88 eM) ee 88°M eee 8 e. Meeeeeee ee eMeMM (888 eM), eeee eeeeeee eee 8.8 e, eee eeeeeee ee ee eeee 8-(8,8-eeeeeeeee-8-eeeeeeeeeee)-8-eeeeeeeeeee; eeeee: 88.8 e (88%); ee 888–888°M.

8-(8,8-Meeeeeeee-8-eeeeeeeeeee)-8-eeeeeeeeeee (88.8 e,888 eeee) eee eeeeeee eeee M8 ee 88.8 eee eee ee 88°M eeee 88% Me(MM)8/M (88 e) eee 8.8 e. Mee eeeeeee eee eeeeee, e eeeeeee eeeeeeee ee eeeeeeee (8 e) eee eeeee, eee eee eeeeeeeeeeeee eee eeeeeeeee ee eeeeee eee e eeeeeee 8 e. Mee eeeeee eeeeeee eee eeeeeeee eeeeeee Meeeee eee eee eeeeeeee eee eeeeeeeeeeee ee eeeeeee ee eee. Meee eee eee eeeeeeeee ee MM8Me8, eeeeee eeee M8M eee ee MeMMM8, eeeee (MeMM8), eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, MM8Me8) ee eeee eeeeeeee eeeee, ee eeeeeeeeeee eeee eMeMM, eeee eee eeeeeee; eeeee: 88 e (88%); ee 888–888°M.

References