Science of Synthesis

Joule, J. A., Science of Synthesis Knowledge Updates, (2010) 2, 81.

The Nenitzescu synthesis consists of reacting a benzo-1,4-quinone with an enamine, the product indole carrying a 5-hydroxy group (‌Scheme 109‌);[‌293‌–‌298‌] see also ‌Table 4‌. When the benzoquinone carries a substituent, mixtures of 6- and 7-substituted indol-5-ols are sometimes obtained; it seems that at whatever stage the 3—3a bond is made, it is made at one of the two positions of the unsubstituted double bond of the benzoquinone. The enamine is generally a 3-aminoacrylate and also generally carries an additional 3-substitutent [e.g., benzo-1,4-quinone (‌307‌) with acrylate ‌308‌ giving indole ‌309‌]. The use of alkyl- and arylaminofumarates leads to indol-5-ols carrying two ester groups on the heterocyclic ring (e.g., ‌307‌ with ‌310‌ giving ‌311‌).[‌298‌] Nenitzescu reactions are carried out in acetone, ethanol, chloroform, and acetic acid; however, nitromethane is strongly endorsed as a suitable solvent.[‌294‌] The use of methyl esters rather than ethyl esters has a favorable effect on yields.[‌294‌] A variation on the Nenitzescu theme is the use of mono-[‌299‌] and bis-imine derivatives of the benzo-1,4-quinone when indol-5-amines can be obtained.[‌300‌,‌301‌]

‌Meeeee 888‌ Meeeeeee ee Meeeeeeeee 8M-Meeee-8-ee Meeeeeeee[‌888‌,‌888‌]

Mee eeeeeee ee eee eeeeeeeeeee eeeeeeee eee eeee ee eeee eeeeee, e.e. eeeeeee ee ee eee 8—8e eeee ee eee 8—8e eeee eeeee ee eeee eeeee; eeeeeeeee/eeeeeeeee eeeee eee eeeeeeeee eeee eeeeeeee.[‌888‌,‌888‌] Me eee eeee ee eeee eeee eeee eee eeeee ee eeeeeeeee eee eee eeeeeee eeeeeeeeee. ‌Meeeee 888‌ eeeee e eeeeeeeeee eeeeeeee, eeee ‌888‌ eeeeee ee ee eeeeeee, Meeeeee-eeee eeeeeeee ee eeeee-8,8-eeeeeee (‌888‌) eeeeeeeeeee eee 8—8e eeee eeeeeeeee eeeeeeeeeeee ‌888‌, eeeeeeeee ee eeeee ee eeeeeeee eeeeeee (ee eee ee eee eeeee eeeeeeeee eeeeeee eeeeeee) eeeeeeee ‌888‌ ee eeeee eeeeeeee-ee-eeeeeeee eeeeeeeeeeeeee eeeeeeee eeeeeeee eee 8—8e eeee eee eeee eee eeeeeeeeeeee eeee (ee ‌888‌). M eeeeeeeee ee ‌888‌ eeee eee eeeeeee eeee ee eeeee eee eee eeeeeeeee ee eee eeeee eeeeeee ‌888‌. Mee eeeeeeeeeeeee eeeeeeee ee eee eeeeeeeee, eeee eeeeeeee eee eeeeeee eeeeeeee eeeeeee ee eee eeeeeeee eeeeeeee, eee eeeeeee eee eee eeeeeeeee eeee eeeeeeee eeeeee eeeee eee eeeeeeee.

‌Meeeee 888‌ Meeeeeeeeee Meeeeeee eee Meeeeeeeee Meeeeeeee[‌888‌,‌888‌]

‌Meeee 8‌ Meeeeee eeee Meeeeeeeee Meeeeeeee[‌888‌,‌888‌–‌888‌]

Meeeeeee Meeeeeeee		Meeeeeeeee	Meeeeee(e)	Meeee (%)	Mee
		MeMM8, ee		88	[‌888‌]
		MeMM, eee		88	[‌888‌]
		MeMM, eeeeee		88	[‌888‌]
		MMMe8, eeeeee		88	[‌888‌]
		MeMM8, ee		88	[‌888‌]
		MeMM8, ee		88	[‌888‌]

Me e eeee eeeeeeeeee, eeeeee eeeeeee, M-eeeeeeeeeeeeee eeeeeeeeeee eeee ee ‌888‌ ee eeeeeeeeeeee eeeeeeeeee eeeee eeee eeee eeeeee, e.e. ‌888‌, eeeee eeeeee eeeeeeee(MM) eeeeeeee/eeeeee­ee(MM) eeeeeeeeeeee ee eeeeeee 8-(eeeeeeeeeeeeee)-8M-eeeee-8-eee eeee ee ‌888‌ ee eeeee eee eeeeeeeeeeee eeeeeeee eeeeeee eeee eee eeeeeee eeeee (‌Meeeee 888‌). Meee e eeeeeee eee(eeeee) eeeeeeeee ee eee eeeeeeee eeee eeeeeeeeeeeeee, eee ee eee eeeee eeee eeeeeee, ee eeeeeeee, M-eeeeeee-8-(eeeeeeeeeeeeee)-8M-eeeee-8-eeeeee eeeeee.[‌888‌]

‌Meeeee 888‌ Meeeeeeeee Meeeeeeee Meeee ee M-Meeeeeeeeeeeee Meeee-8,8-eeeeeee Meeeeeeee[‌888‌]

Meeeeeeeeeee Meeeeeeee

Meeeee 8-Meeeeee-8-eeeeeeeee-8,8-eeeeeeee-8M-eeeeee-8-eeeeeeeeeee (‌888‌); Meeeeee Meeeeeeee:[‌888‌]

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

M eeee ee 8-eeeeeeeeeee-8,8-eeeeeee (8.88 e, 88 eeee) ee MeMM8 (88 eM) eee eeeee ee eeeeee (M)-8-(eeeeeeeeeeeeee)eee-8-eeeeee (8.8 e, 88 eeee) eeeeeeeee ee MeMM8 (88 eM) ee ee. Me eeeeeeeee eee eeeee eee eeeeeeee eee eee eeee eeeeee eeee. Meeee 88 e, eee eeeeeee eee eeeeeeeee ee eeeeeeeeee eee eeeee; eeeee: 8.88 e (88%); ee 888–888°M.

References