0 Hits

  • Previous / Next

You are using Science Of Synthesis as a Guest.
Please login to access the full content or check if you have access via Method 1: From N-Acyl-2-arylethylamines: The Bischler–Napieralski Synthesis

DOI: 10.1055/sos-SD-015-01146

Álvarez, M.; Joule, J. A.Science of Synthesis, (200515716.

The widely used BischlerNapieralski 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 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 MeeeeeeeMeeeeeeeeee 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 MeeeeeeeMeeeeeeeeee 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 MeeeeeeeMeeeeeeeeee Meeeeeeee Meeeee 8,8-Meeeeeeeeeeeeeeeeeee[‌888‌,‌888‌,‌888‌‌888‌]

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, 888°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; 88e, 88eeee] eee MMMe8 (88e, 8.8eee) eee eeeeee ee eeeeeeeee eee eeeeeee (88eM) eee 8e. 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: 88e (88%); ee 8888°M.

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

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

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

8-(8,8-Meeeeeeeeeeeeee)-M-(eeeeeeeeeeeeeeeee)eeeeeeeeee (8.8e, 88eeee) eee MMMe8 (8.8eM, 88eeee) ee eeeeeeeeee ee MeMM (88eM) eeee eeeeeeee eee 8e. 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: 8.8e (88%); ee 888°M.

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

Mee 8,8-eeeeeeeee-8-(eeeeeeeeeeeeeeeee)eeeeeeeeeeee (8e, 88eeee) ee MeMM (888eM) eee eeeeeeee eeee eeeeeeeee eeeeeee (88eM) eee 8e. 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: 8.8e (88%); ee 888°M.