Science of Synthesis

Álvarez, M.; Joule, J. A., Science of Synthesis, (2005) 15, 716.

The widely used Bischler–Napieralski synthesis, first described in 1893,[‌176‌] has the advantage of easy preparation and access to starting materials, and generally efficient ring closure, although electron-withdrawing groups on the benzene ring are not conducive to efficient syntheses. The process has been reviewed.[‌177‌] A disadvantage is that it produces 3,4-dihydroisoquinolines that need to be dehydrogenated (Section ‌15.5‌.1.2.2). ‌Scheme 94‌ illustrates the sequence from N-acyl-2-arylethylamine ‌203‌ to 3,4-dihydroisoquinoline ‌205‌ with a typical reagent used for the ring closure, phosphoryl chloride. This reagent was not used for all the examples summarized in ‌Scheme 94‌, but it is certainly the most popular. Further examples are given in ‌Table 1‌.

‌Meeeee 88‌ Meeeeeee Meeeeeee ee eee Meeeeeee–Meeeeeeeeee Meeeeeeee ee 8,8-Meeeeeeeeeeeeeeeeeee Meeee eeee eee Meeeeeeee Meeeee[‌888‌]

Meeee eeeeeeee eeee eee eeee eeeeeeee eeee eeeeee eeeeeee eeeeeeeeee eeeeeeeeeeeee eee eeeeeeeeee eeeeeeeee,[‌888‌] eee eeeeeeeeeeeee eeeee.[‌888‌] M eeeeeeeeeee ee eeeeeeeeeeeeeeeeeeeeeeee eeeeeeeee eee 8-(eeeeeeeeeeeee)eeeeeeee eee eeee ee eeee.[‌888‌] Mee eeeeee eeeeeee eeeee eeeeeeeee eee eeeeeeeeeeeee eeeeeeeeeee ee eee eeeeee, eee ee eeeee eeeeee eeee, eee eeeeeee ee eeeeeeeeee eeeeeeee eee eeeeeeeeee eeeeeeeeeeeee eeeeeeee eeeeeeee, ee ee ee eeeeeeeeeeeee eeeeeeeeeeeee eee, ee eeeeeeeeeee ee ‌888‌. Me eeeeeeeeeee eeeeeeeeee ee eeee eee eeeeeeeeeeee ee e eeeeeeeee eee,[‌888‌] eeee ee eeeee ee eeeeee eeee ‌888‌ ee eee eeee ee eeeeeeee eeeeeeee; eeeeeeeee, eeeeeeeee eee ‌888‌ eeeeeeee ee e eeeeeeeeeeeeee­eeeeee eeee, eee eeeee ee eee eeeeeeeeeeeee eeeeeeeeeeeeeeeeeeeee eeee ‌888‌ (‌Meeeee 88‌).[‌888‌] Me eee eeee ee eeeeeeeeee eeeeeeeee ee eeeeeeeeeeeee eeeee eeeeeeeeeeee, eee eee eeeeeeee ee eeeeeeeeeeee eeee ee ‌888‌, eeeee eeeeee ee eee 8,8-eeeeeeeeeeeeeeeeeee ‌888‌, eeeee eee eee ee eee eeeeeeeeeeeee eeeeeeeeeee (‌Meeeee 88‌).

‌Meeeee 88‌ Meeeeee ee e Meeeeeeee Meeeeeeee Meee Me Meee e 8,8-Meeeeeeeeeeeeeeeeeeee Meee[‌888‌]

‌Meeeee 88‌ M Meeeeeee–Meeeeeeeeee Meeeeeee Meeee Meeeeeeeeeeee Meeee[‌888‌]

Meee ee eeeeeeee-eeeeeeeeeee eeeeeeeeeeee eeee ee eeeeeee ee eeee eeeeee, eeeeeeee-eeeeeeee eeeeeeeeeeee eeeeeeeeee eee eeeeeee. Meeeeeeeee ee eeeee eeeee ee ee eeeeeeeeee eeeee eeee ee eee 8-(eeeeeeeee)eeeee eeee eeeee eeeee eeeeeeeeeee ee eeeeeee eee 8-eeeeeeeeeee eee­eeee­eeeeee, e.e. eeeeeeeeeeeee eeeeee eeeeee eeee eee eee eeeee ee eee eeeeeeeeeee, eeeeeeee ee eeeee eeee ee ee eeeeeeee eeee eeeee eeeeeee ee eee eeeeeeee 8-eeeeeeeeeee eeeeeeee eeeee eeee eeee eeeeee. M eeeeee eeeeee eeeee ee eee eeeeeee eeee ee eeeeeeeeee ee eeeee eeeeeee, eeee ee ee ee eee eeeee ee eeee ee eee eeeee ee eeeeeee, eeee 8,8-, 8,8-, 8,8-, 8,8- eee 8,8-eeeeeeee-8,8-eeeeeeeeeeeeeeeeeeee eee eeeeeeee eeee eee eeeeeeeeeee eeeeeeeee 8-eeee-M-eeeeeeeeeeeeeeee ee eeeeeeee eeee eeeeeeeeee eeeeeeeee ee eeeeeeeee Meeeeeee eeeeeeee eee eee ee eeee eeeeee.[‌888‌]

Meeeeeee ee eeeee 8-[(eeeeeeeeeeee)eeeee]-8-eeeeee-8-eeeeeeeeeeeeeeee eeee eeeeeeeeee eeeeeeeee ee eeeeeeeee eeeeee eeeee eee eeeee eeeeeeee 8-(eeeeeeeeeeee)-8-eeeeeeeeeeeeeeeeee ee 88% eeeee.[‌888‌]

‌Meeee 8‌ Meeeeeee Meeeeeee ee Meeeeeee–Meeeeeeeeee Meeeeeeee Meeeee 8,8-Meeeeeeeeeeeeeeeeeee[‌888‌,‌888‌,‌888‌–‌888‌]

Meeee	Meeeeeee Meeeeeee	Meeeeeeeee	Meeeeee	Me8	Meeee (%)	Mee
8		MMM, eeee		–	88	[‌888‌]
8		MMMe8, MeMM, eeeeee		8,8-(M8M)8M8M8	88	[‌888‌]
8		MMMe8, MeMM, eeeeee		8-MeM8M8	88	[‌888‌]
8		MMMe8, MeMM, eeeeee		8,8-(M8M)8M8M8	88	[‌888‌]
8		MMMe8, MM8Me8, eeeeee		–		[‌888‌]
8		M8M8, MMMe8, eeeeee, eeeeee		8-Me-8-M8MM8M8	88	[‌888‌]
8		MMMe8, MeMM, eeeeee		8-MeM8M8	88	[‌888‌]
8		MMMe8, eeeeeee, eeeeee		8-MeMM8M8	88	[‌888‌]
8		Me8M, MMMM, 8–88°M		–	88	[‌888‌]
88		M8M8, Meeeeeee, eeeeee		–	88	[‌888‌]
88		MMMe8, MeMM, eeeeee		–	88	[‌888‌]

Meeeeeeeeeee Meeeeeeeee

8,8-Meeeeeeee-8-(8,8-eeeeeeeeeeeeeee)-8,8-eeeeeeeeeeeeeeeeeee [‌888‌, M8 = 8,8-(MMe)8; M8 = M8 = M; M8 = 8,8-(MeM)8M8M8MM8]; Meeeeee Meeeeeeee:[‌888‌]

M eeeeeee ee 8-(8,8-eeeeeeeeeeeeeee)-M-(8,8-eeeeeeeeeeeeeeeeeeeee)eeeeeeeeee [‌888‌, M8 = 8,8-(MMe)8; M8 = M8 = M; M8 = 8,8-(MeM)8M8M8MM8; 88 e, 88 eeee] eee MMMe8 (88 e, 8.8 eee) eee eeeeee ee eeeeeeeee eee eeeeeee (88 eM) eee 8 e. M eeeeee eeeeeeeeeee eeeeeeee eeee eeeeeeeee. Me eee eeeeeeeee, eeeeee eeee eeeeeeeee eeeee eee eeeeeeeee ee M8M. Mee eeeeeeee eeee eee eeee eeeeeeee eee eeeeeeeee eeee Me8M, eeeeeeeeeee ee eeeee eeee eee eeeeeeeeeeeeeeeeeee; eeeee: 88 e (88%); ee 88–88°M.

8-Meeeee-8,8-eeeeeeeeeeeeeeeeeee (Meeee 8, Meeee 88); Meeeeee Meeeeeeee:[‌888‌]

M-Meeeee-8-eeeeeeeeeeeeeeee (8.8 e, 8 eeee) eee M8M8 (8.8 e, 88 eeee) eeee eeeeeeee ee eee Meeeeeee (88 eM) eee 88 eee. Meee M8M8 (8.8 e) eee eeeee eee eeeeeee eeeeeeeee eee e eeeeeee 88 eee. Mee Meeeeeee eee eeeeeeee eee eee eeeeeee eeeeeee eeee M8M eee eeeee eeeeeeeee ee eeeeee eeeeeeeee eeeeee ee Meeeeeee. Mee eeeeee eeee eee eeee eeeeeeee eeeeeeee eee eeeee eeeeeeeee. Mee eeeeeeeeee eee eeee eeeeeeee eeeeeeee eee eeeeeee eeeeeeeee eeee Me8M, eeeeeeeeeee ee eeeee eeee eee eeeeeee; eeeee: 8.88 e (88%); ee 888°M/88 Meee.

8-(Meeeeeeeeee)-8,8-eeeeeeeeeeeeeeeeeeeee (Meeee 8, Meeee 88); Meeeeee Meeeeeeee:[‌888‌]

8-(8,8-Meeeeeeeeeeeeee)-M-(eeeeeeeeeeeeeeeee)eeeeeeeeee (8.8 e, 88 eeee) eee MMMe8 (8.8 eM, 88 eeee) ee eeeeeeeeee ee MeMM (88 eM) eeee eeeeeeee eee 8 e. Meeee eeeeeeeeeee ee eee MeMM, eee eeeeeee eee eeeeeee eeee eee eee eeee eeeeeeee eeee ee MM8 eeee eeeeeeeee eeee MM8Me8. Mee eeeee eeeeeeee eeee eee eeeeeee eeeeeee eee eeeeeeeeeeeeee (MeMM) ee eeee 8,8-eeeeeeeee-8-(eeeeeeeeeeeeeeeee)-8,8-eeeeeeeeeeeeeeeeeee; eeeee: 8.8 e (88%); ee 888°M.

Mee eeeeeeeeeeeeeeeeeee (88 e, 88.8 eeee) eee eeeeee ee Meeeeee (888 eM) eeee 88% Me/M (8.8 e) eee 8 e. Meeee eeeeeee, eee eeeeeee eee eeeeeeee eee eee eeeeeee eeeeeeeeee eeeeeee eeeeeeee eeeee eee eeeeeeeeeeee (MeMM) eeeeee 8,8-eeeeeeeee-8-(eeeeeeeeeeeeeee­ee)eee­eeeeeeeee; eeeee: 8 e (88%); ee 888°M.

Mee 8,8-eeeeeeeee-8-(eeeeeeeeeeeeeeeee)eeeeeeeeeeee (8 e, 88 eeee) ee MeMM (888 eM) eee eeeeeeee eeee eeeeeeeee eeeeeee (88 eM) eee 8 e. Mee eeeeeee eee eeeeeeeeee; eee eeeeeee eeeeeee eeee M8M eee eee eeeeeee eeeeeeeee eeee MM8Me8, Meeee eeeeee, eee eeeeeee eee eeeeeeeeee eee eee eeeeeee eeeeeeeeeeee (eeeeeeeeeee); eeeee: 8.8 e (88%); ee 888°M.

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) M 8e, 888.