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25.6.6.4 Method 4: The Vilsmeier–Haack Reaction

DOI: 10.1055/sos-SD-025-00443

Schall, A.; Reiser, O.Science of Synthesis, (200725609.

The application of dimethylformamide or N-methylformanilide in combination with phosphoryl chloride, known as the VilsmeierHaack reagent, is arguably the most useful method for the direct formylation of arenehydrogen bonds. The reaction mechanism can be viewed as a special type of a FriedelCrafts acylation: the formyl group of the amide reacts with phosphoryl chloride, sometimes assisted by addition of pyridine, to form a mixture of iminium salts 7, which undergo an electrophilic substitution with the arene (Scheme 5). The adducts 8 formed in this process are subsequently hydrolyzed to give the arenecarbaldehydes 9.

Meeeee 8 Mee MeeeeeeeeMeeee Meeeeeee

Meee eeeeeeeeeeeeeeeee ee eee eeeeeeeeeee eeeee, ee eee ee eeeeeeeeeeee eeee ee eee eeeeeee ee eee eeee eeee. Me M-eeeeeeeeeeeeeeeee ee eeeeeeee ee eee eeeeeeeeeee eeeee, eeeeeeeeeee eeeeeeee eeee ee 8,8-eeeeeeeeeeeeee eee eeeeeeee eee eeee eeeeeee. Meeeeee ee eeeeeeeeee eeeeeeee, eeeee eeee eeeeeeeee eeee ee eeeeeee eeeeeeee, eeeeee eeeeeeee, ee eeeeeeee eee ee eeeeeeee ee eeee, eee eeee eee eeeee eeeeeeeeeeeeeee eeee eeeeeee ee eeeeeeee eeee eeeeeeeee, eeee eeeeeeeeee, eee eeeeee. Meeeeeee, eee eeeeeee eee ee eeeeeeee ee eeeeeeeeeee eeeeee eeeee eeee eeeeeeeeee ee eeee eeeeeee, eeeeee ee eeeeeee eeeeee.

Meee eee MeeeeeeeeMeeee eeeeeeee, eeeeeeee-eeee eeeeee, eeeeeeeee eeeeeeeee, eeeeeee eeeeeeeeeee eeeeeeee [Meeeee 88 eee 8 (Meeeeee 88.8.8.8.8), Meeeee 8 (Meeeeee 88.8.8.8.8), eee Meeee 88 (Meeeeee 88.8.8.8.8)]. Meeeeeeeeee eeeeeeee eeeeeee eeeeeee ee eeeee eee eeeeeeee eeeee eeeeeeeeeeee eeee ee ee eeeeee ee e eeeeeeeeeeee eeeee (Meeeee 88), e.e. ee eee eeeeeeeee ee 88 (Meeeee 8). 8,8,8-Meeeeeeeeeeeeeee ee eee eeeeeeeeee eeeeeeeeee eee eeeeee eeeeee ee eeeeeeeeee eeee eee ee eeeeeeeeeeee eeeeeeeeee, eeeee e eeeeeeeeeee ee eeeeeeeeeeeeeeeee eee eeeeeeeeeeeeeeeeeeeeeeee eeee.[‌88‌] Me eeeeeeee, eeeeeeeeee eeeeee eeeeeee MeeeeeeeeMeeee eeeeeeeee eeeeeee ee eee eeeeeee ee eeeeeeeeee eeeeeeeeeeee eee ee eeeee eeeeeee eeeeeeeeeee (Meeee 8). Meeeeeee, eeeeeeee-eeee eeeeeeeee (Meeee 8) eee eeeeeee eeeeeeeeee eeeee MeeeeeeeeMeeee eeeeeeeeee ee eeee. Meeeeeee eeeeeee eeeeee eee eeee eeeeeeeee eeee eeeee eeeeeeeeeeeee eeeeeeeee eeeee eee eeeeeeee eeeeeeeeee.

Meeeeeeee eee eeeee eeeeeeeeee eeeeeee eeee eeeeeeeee eee eeeeeeeeeeeeeeee ee ee eeeeeeeeeeeee eeeeeeeeeeee eeeeeeee, eee ee eee eeeeee eeee eee eeeeeee eeee ee eeeeeeee ee eee eeeeeeeeee eeee eeeeeeeee ee eee eeeeeeeeeeeeee eeeee eeeeeeeee, e.e. eeee-eeeeeeeeeee eeeeeeee eee eeeeee eeee eeeeee eeeeeeeeee eeee eee eeeeeeeeeeeee eeeee-eeeeeeeeeee eeeeeee.

Me e eeeeeeeeeeeeeee eeeeeeeeeee ee eeeeeee ee eee eeeeeeeee, eeeeeee, eee eeeeeeeeeee eeeeeeee eeee eeee-eeeeeeeeeeee ee eeee eeeee, eeeeeeeeeeee ee eee eeeeeeee ee eeeee eeeeee eeeeeee (Meeeee 8).[‌88‌] Me eeee eeeee, eee eeeeeeeeeee ee eeeeeeeeee eee eeeeeeeee ee eeeeeeee-eeeeeeee eeeeee ee eeee eeee eeeeeeeeee, e.e. eee eee eeeee ee eeeeeeeeee eee eeeeeeeeee eeeeeeeeeee ee eeee eeeeeeee ee eeee eeeeeeeeeee eeeeeeee.

Meeeee 8 Meeeeeeeeee eeee Meeeeeeeeeeeeee-Meeeeeeeeee Meeeee[‌88‌]

Meeee 8 Meeeeeeeeeeeeee Meeeeeee ee Meeeeeeeee ee eee MeeeeeeeeMeeee Meeeeeee[‌8‌,‌88‌‌88‌]

Meeee Me8 M Meeeeeeeee Meeee (%) Mee
8 8-MeMM8M8 M MMM (8.8 eeeee), MMMe8 (8.8 eeeee), eeeeee, 88e 88 [‌88‌]
8 8-Me8MM8M8 M MMM, (8.8 eeeee), MMMe8 (8.8 eeeee), 88°M, 8e, eeee 8888°M, 8e, eeee ee, 88e 88 [‌88‌,‌88‌]
8 8-Me8MM8M8 M MMM (8.8 eeeee), MMMe8 (8.8 eeeee), eeeeee, 8e, eeee 8888°M, 8e, eeee ee, 88e 88 [‌88‌]
8 8-Me8MM8M8 M MMM (8.8 eeeee), (Me8MM)8M (8.8 eeeee), 88°M, 88e 88 [‌88‌,‌88‌]
8 8-Me8MM8M8 M MeM(Me)MMM (8.8 eeeee), MMMe8 (8.8 eeeee), 8888°M, 8e 88 [‌8‌]
8 8-[Me(MM8)8]8MM8M8 M MMM (8.8 eeeee), MMMe8 (8 eeeee) 88 [‌88‌]
8 Me MeMe8 MeM(Me)MMM (8.8 eeeee), MMMe8 (8.8 eeeee), 88°M, 8e 88 [‌88‌]

Meeee 8 8,8-Meeeeeeeeeeee Meeeeeee ee Meeeeeeeee ee eee MeeeeeeeeMeeee Meeeeeee[‌88‌,‌88‌,‌88‌‌88‌]

Meeee Me8 M Meeeeeeeee Meeee (%) Mee
8 M MMM (8.8 eeeee), MMMe8 (8.8 eeeee), eeeeee, 88e 88 [‌88‌,‌88‌]
8 8,8-(MeM)8M8M8 M MeM(Me)MMM (8.8 eeeee), (Me8MM)8M (8.8 eeeee), 888°M, 88e 88 [‌88‌]
8 M MMM (8.8 eeeee), MMMe8 (8.8 eeeee), 888°M, 8.8e 88 [‌88‌]
8 M MMMe8, MeM(Me)MMM, 8888°M, 8e 88 [‌88‌]
8 M MeM(Me)MMM, MMMe8 88 [‌88‌]
8 M MMM (88 eeeee), MMMe8 (8 eeeee), eeeeeeee (8.8 eeeee), 88°M, 88e 88 [‌88‌]
8 8-MeMM8M8 MeMe8 MeM(Me)MMM (8.8 eeeee), MMMe8 (8.8 eeeee), 88°M, 8e 88 [‌88‌]

Meeee 8 8,8-Meeeeeeeeeeee Meeeeeee ee Meeeeeeeee ee eee MeeeeeeeeMeeee Meeeeeee[‌88‌,‌88‌,‌88‌,‌88‌,‌88‌‌88‌]

Meeee Me8 M Meeeeeeeee Meeee (%) Mee
8 8,8-(MM)8M8M8 M MMM (8.8 eeeee), (Me8MM)8M (8.8 eeeee), 88°M, 8e 88 [‌88‌]
8 M MMM (8.8 eeeee), MMMe8 (8.8 eeeee), eeeeee, 88e e [‌88‌]
8 M MMM, MMMe8, 88°M 88 [‌88‌,‌88‌]
8 M MMM, MMMe8 88 [‌88‌]
8 8,8-(MeM)8M8M8 M MeM(Me)MMM (8 eeeee), MMMe8 (8 eeeee), 8888°M, 8e 88 [‌88‌]
8 M MeM(Me)MMM, MMMe8 88 [‌88‌]
8 M MeM(Me)MMM (8.8 eeeee), MMMe8 (8.8 eeeee), 8888°M, 8e 88 [‌88‌]
8 8-Mee MeMe8 MeM(Me)MMM (8.8 eeeee), MMMe8 (8.8 eeeee), 88°M, 8e 88 [‌88‌]

e Meeee eee eeeeeeee.

Meeee 8 8,8-Meeeeeeeeeeee Meeeeeee ee Meeeeeeeee ee eee MeeeeeeeeMeeee Meeeeeee[‌88‌,‌88‌,‌88‌,‌88‌,‌88‌]

Me8 M Meeeeeeeee Meeee (%) Mee
M MMM (8.8 eeeee), MMMe8 (8.8 eeeee), eeeeee, 88e e [‌88‌]
8,8-(MeM)8M8M8 M MMM (8.8 eeeee), (Me8MM)8M (8.8 eeeee), 888°M, 88e 88 [‌88‌,‌88‌]
M MMM (eeeeeee), MMMe8 (8.8 eeeee), 88888°M, 8.88e 88 [‌88‌]
8-Mee MeMe8 MeM(Me)MMM (8.8 eeeee), MMMe8 (8.8 eeeee), 88°M, 8e 88 [‌88‌]
8-MeMM8M8 MeMe8 MeM(Me)MMM (8.8 eeeee), MMMe8 (8.8 eeeee), 88°M, 8e 88 [‌88‌]
8-MeM8M8 MeMe8 MeM(Me)MMM (8.8 eeeee), MMMe8 (8.8 eeeee), 88°M, 8e 88 [‌88‌]

e Meeee eee eeeeeeee.

Meeee 8 Mee-, Meeee-, eee Meeeeeeeeeeeeeee Meeeeeee ee Meeeeeeeee ee eee MeeeeeeeeMeeee Meeeeeee[‌88‌,‌88‌‌88‌]

Meeee Me8 Meeeeeeeee Meeee (%) Mee
8 MMM (eeeeeee), MMMe8, (8.8 eeeee), 888°M, 88e 8888 [‌88‌]
8 MMM, MMMe8, 888°M, 88e 88 [‌88‌]
8 MMM, MMMe8 (8.8 eeeee), ee, 8.8e 88 [‌88‌]
8 MMM, MMMe8, 888°M, 88e 88 [‌88‌,‌88‌]
8 MeM(Me)MMM, MMMe8, 888°M, 8e 88 [‌88‌,‌88‌]
8 MeM(Me)MMM, MMMe8, ee, 88e 88 [‌88‌‌88‌]
8 MMM, MMMe8 88 [‌88‌]
8 MMM, MMMe8, ee, 8e 88 [‌88‌]
8 MMM, MMMe8, MM8Me8, eeeeee, 88e 88 [‌88‌]
88 MeM(Me)MMM, MMMe8, eeeeeeeeeeeee, 88°M, 8e, eeee 8888°M, 8e 88 [‌88‌]
88 MMM, MMMe8, 888°M, 88eee 88 [‌88‌]
88 MMM, MMMe8, 8e, 88°M 88 [‌88‌]
88 MMM, MMMe8, 88°M 88 [‌88‌]
88 MMM, MMMe8, 88°M 88e [‌88‌,‌88‌]

e Meeeeeeeeeee ee eee MM eeeee eeee Me eeeeee ee eeee 8-(eeeeeeeeeeee)-8,8-eeeeeeeeeeeeeeeeeeeee.

Meeee 8 Meeeeeeeee Meeeee ee Meeeeeeeee ee eee MeeeeeeeeMeeee Meeeeeee[‌88‌,‌88‌,‌88‌,‌88‌,‌88‌‌88‌]

Meeee Me8 M8 Meeeeeeeee Meeeee (%) Mee
8 8-eeeeeeee MMM, Me8M 88 [‌88‌]
8
8

MMM, MMMe8
MeM(Me)MMM, MMMe8
88
88
[‌88‌]
[‌88‌]
8
8
8
8
8
MMe
MMe
MMe
MMe
MMe8
MMM, (Me8MM)8M, 88°M, 88e
MeM(Me)MMM, MMMe8
MeM(Me)MMM, MMMe8
MeM(Me)MMM, MMMe8
MMM, MMMe8
88
88
88
e.e.
e.e.
[‌88‌]
[‌88‌‌88‌]
[‌88‌]
[‌88‌]
[‌88‌]
8 MMM, MMMe8, 88°M, 88e 88 [‌88‌]
88 MeM(Me)MMM, MMMe8, 888°M, 8e 88 [‌88‌,‌88‌,‌88‌]
88
88
88
88
M
Me
e-Me
Me
MMM, MMMe8
MMM, MMMe8
MMM, MMMe8
MMM, MMMe8
8888
88
88888
88888
[‌88‌,‌88‌]
[‌88‌‌88‌]
[‌88‌]
[‌88‌]
88 MMM, MMMe8 88 [‌88‌]

e e.e.=eee eeeeeeee.

Meeee 8 Meeeeeeeeeee ee Meeeeeeeee ee eee MeeeeeeeeMeeee Meeeeeee[‌88‌,‌88‌‌88‌]

Meeeeeeee M8 Meeeeee Meeeeee Meeee (%) Mee
M
M
Me
Me
eMe
MMM, MMMe8
MMM, (Me8MM)8M
MMM, MMMe8
MMM, MMMe8
MMM, MMMe8
88
88
88
88
88
[‌88‌]
[‌88‌]
[‌88‌]
[‌88‌]
[‌88‌]
M
Me
Me
Me
MMe
MeM(Me)MMM, MMMe8
MeM(Me)MMM, MMMe8
MeM(Me)MMM, MMMe8
MeM(Me)MMM, MMMe8
MMM, (Me8MM)8M
88
88
88
8888
88
[‌88‌‌88‌]
[‌88‌‌88‌]
[‌88‌,‌88‌]
[‌88‌,‌88‌,‌88‌]
[‌88‌]
MMM, MMMe8 88 [‌88‌]
MMM, MMMe8 88 [‌88‌,‌88‌]
MMM, MMMe8 888 [‌88‌‌88‌]


MMM, MMMe8 (8.8 eeeee), 8°M
MMM, MMMe8 (8.8 eeeee), 88°M
88e
88e
88e
[‌88‌]
[‌88‌]
[‌88‌]
M
Me
Me
MeM(Me)MMM, MMMe8
MeM(Me)MMM, MMMe8
MeM(Me)MMM, MMMe8
88
88
88
[‌88‌]
[‌88‌]
[‌88‌]

e M8=MMM; M8=M.

e M8=M; M8=MMM.

e M8=M8=MMM.

Meeeee 8 Meeeeeeee ee 8-[Mee(eeeeeeeeeeeeeeeeeeee)eeeee]-8-(eeeeeeeeeeeeeeeeeeeee)eeeeeeeeeeee Meeee Meeeeeee[‌88‌]

Meeeeeeeeeee Meeeeeeee

8-(Meeeeeeeeeeee)eeeeeeeeeeee (Meeee 8, Meeee 8); Meeeeee Meeeeeeee:[‌88‌]

MMM (8 eeeee) eee M,M-eeeeeeeeeeeeeee (8 eeeee) eeee eeeeeee eeeee eeeeeee eeee MMMe8 (8 eeeee). Meeeeeeee eeeeeeee, eee eeeeeee eee eeeeeee eee 8e ee 88°M eee eeee eeeeee ee 8888°M. Meeee eeeeeeee eee 88e, eee eeeeeee eee eeeeeeeee eeeee eee MMe, eeeeeeee ee 8888°M, eee eeee eeee eeeee eeeee MeMM. Meeeeeeeee eeee MMMe8 eee eeeeeeeeee eeeeeeeeeeee (88Meee) eeeeeeee eee eeeeeee; eeeee: 88%.

8,8-Meeeeeeeeeee-8-eeeeeeeeeeee (Meeee 8, Meeee 8); Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeeee eeeeeeee eeeeee eeeeeeeee eeee eeeee eeeeeeeee eeeee eeeeeee ee eeeeeeeee eeeee. Me ee eeeeeeeee eeeeeeeeeee ee eee eeeeeee.

Me MeM(Me)MMM (888e, 8.88eee) eeeeee ee ee eeeeeeee eeee, MMMe8 (88.8e 8.88eee) eee eeeee eeeeeeee eeee eeeeeeee. Meeee eeeeeeeeee ee eee eeeeeeee, eee eeeeeee eee eeeeeee ee eeeee ee ee eee 8e eee eeee eeeeee ee 8888°M eee 8e eeeee eeeeeee eeeeeeee (8888Meee). Me eee eeeeeeeee eeeeee eeeeeee, 8,8-eeeeeeeeeeee (88.8e, 8.88eee) eee eeeee eee eeee ee 88°M. Meeee eeeeeeeeee ee eee eeeeeeee, eee eeeeeee eee eeee ee 88°M eee 88eee, eeeeee eeee eee eeeee, eee eeeeeee ee eeeee eee 8e. Mee eeeeeeeee eeeeeee eee eeee eeeeeeeee eeee eeeeeee. Meeeee eeeeeeeeeeee eeeeeee eeeeeeee eeeeeee, eee eeeeeeeeee eeeeeeeee ee 8888°M/88Meee eeeeeeeee eeeeeeeee 8,8-eeeeeeeeeeee, eee eee eeeeeeeeee eeeeeeeee ee 888888°M/88Meee eeeeeeeee 8,8-eeeeeeeeeeee-8-eeeeeeeeeeee (eeeeeeeee); eeeee: 88% (eeeee ee eee eeeeee ee MeM(Me)MMM eeee) (88% eeeeeeeeeee eeeee ee eee eeeeee ee 8,8-eeeeeeeeeeee eeeeee eeeeeee).

8,8-Meeeeeeeeeeeeeeeeeeee (Meeee 8, Meeee 8); Meeeeee Meeeeeeee:[‌88‌]

MMMe8 (888e, 8eee) eee MeM(Me)MMM (888e, 8eee) eeee eeeeee ee e 8-M eeeee-eeeeee eeeee eee eeeeeee ee eeeee eee 88eee. Me eeee eeeeeee eee eeeee, eeee eeeeeeee, 8,8-eeeeeeeeeeeeeeee (888e, 8eee) eeee 88eee, eeeee eee eeeeeeee eeeeeeeeeee eee eeee ee 88°M ee e eeee eeeee eeee. Meee eeeeeeee eee eeeeeeee, eee eeee eee eeeeeee eee eee eeeeeee eee eeeeeee eee 8e eeeeee eeeee eeee eee eeeeeeeeeee eeee ee 88°M. Mee eeeeee, eee eeeeeee eee eeeeeee ee eeeee eeeeeeeee eee eeee eeeeee eeeeee eeee eeeeeeee eeee eeee M8M (8.8M). Mee eeeeeeeee eeeee eee eeeeeeeee eee eeeeee eeee eeee M8M. Mee eee eeee eee eeeeeeeee ee eeee eeeeeee (888eM) (MMMMMMM: eeeeeeeeee), eee eee eeeeeee eeeee eee eeeeeeeee eee eeeeee eeee eeeeeee (88eM). Mee eeeeeeee eeeeeeee eeee eeeeeeeeeeee eee eeeeeeeee eeee e Meeeeee eeeee, eeeeee eee eeee eeeeeeee; eeeee: 888e (88%); ee 888°M/8.8Meee; ee 8888°M.

Meeeee 8-Meeeee-8,8-eeeeeeeee-8-eeeeeeeeeeeeee (Meeee 8, Meeee 8):[‌88‌]

Me e eeee ee MMM (8.88M, 8.88eee) ee MM8Me8 (8M) eee eeeeee eeeee MMMe8 (8.888M, 8.88eee). Mee eeeeeee eee eeeeeee ee 88°M eee 8.8e. M eeee ee eeeeee 8,8-eeeeeeeee-8-eeeeeeeeeeeeee (888e, 8.88eee) ee MM8Me8 (8.8M) eee eeeee eeee 88eee. Meeee eeeee eeeeeeee eee 88e, eee eeeeeee eee eeeeee eee eeeeee eeee eee eeeee (8M). Mee eeeeeee eee eeeeeeeee eeee MM8Me8 (8.8M), eee eee eeeeeee eeeee eee eeeeee eeee ee Me8MM8 (8M) eee M8M (8×8M), eeeee, eee eeeeeeeeeeee. Mee eeeee eeeeeee eee eeeeeeeeeeeeee (MeMMe/eeeeee) ee eeee eee eeeeeeee ee e eeeee eeeee; eeeee: 888e (88%); ee 888- 888°M.

8-[Mee(eeeeeeeeeeeeeeeeeeee)eeeee]-8-(eeeeeeeeeeeeeeeeeeeee)eeeeeeeeeeee (88):[‌88‌]

Me e eeee ee eee eeeee (8.88e, 8.88eeee) eee eeeeeeee (888ee, 8.88eeee) ee MMM (8.88e, 88.8eeee) eee eeeee MMMe8 (8.88e, 88.8eeee) eeeeeeee ee 8°M eeee 888eee. Mee eeeeeee eee eeeeee eee 88e ee 88°M eeeee eeeeeeeeee. Mee eeeeeeee ee eee eeeeeeee eee eeeeeeeee ee eee eeeeeeeeeeeee ee eee eeeeeeee eeeeeeee ee MMM. Meeee eeeeeeeeee, eee eeeeeee eee eeeeee eeee eee eeeee. Meeee eeeeeeeeee eeee MeMMe, eee eeeeeee eeeee eee eeeeee eeee eeeee eee eeeee (MeMM8). Meeee eeeeeee ee eee eeeeeee eeeee eeeeeee eeeeeeee, eee eeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, MM8Me8/MeMMe 8:8). Meee eeee eee eeeeeeee 88 ee eeeee eeeeeeee; eeeee: 8.88e (88%); ee 8888°M.

References