[80984-92-5] · C8H9Cl3NO2P · N-Methyl-N-phenyl(chloromethylene)ammonium Phosphorochloridate · (MW 288.50)
Alternate Name: N-methylformanilide-phosphorus oxychloride complex.
Physical Data: see N-Methylformanilide (MFA) and Phosphorus Oxychloride.
Form Supplied in: prepared in situ.
Handling, Storage, and Precautions: phosphorus oxychloride is corrosive and lachrymatory. N-Methylformanilide is toxic and harmful by absorption. The iminium salt reacts vigorously with water. Use in a fume hood.
Simple unactivated aromatic systems do not react with most Vilsmeier reagents (the adduct from N,N-Dimethylformamide-Trifluoroacetic Anhydride has been reported to formylate unactivated systems;5) electron-rich aromatic systems undergo monoformylation with MFA-POCl3 in moderate to good yields.1 Thus anthracene gives 9-anthracenecarbaldehyde (eq 1);6 pyrene gives 3-pyrenecarbaldehyde (53%);7 and azulene gives 1-azulenecarbaldehyde (eq 2).8 Recent reports suggest that the adduct of Pyrophosphoryl Chloride (P2O3Cl4) and MFA is a more effective formylating agent. For example, formylation of anisole with MFA-P2O3Cl4 gives p-methoxybenzaldehyde in 72% yield, compared to only 34% with MFA-POCl3.9
Heterocyclic systems have been formylated in moderate to good yields using MFA-POCl3, e.g. thiophene (eq 3)3,10 and indole (eq 4).4 It is notable that poor yields of 3-indolecarbaldehyde (highest yield 37%) are obtained in the absence of a solvent.4
Styrene and several of its derivatives have been converted into the corresponding a,b-unsaturated aldehydes (eq 5).11 A series of 1,1-diarylethylenes have been similarly converted into a,b-unsaturated aldehydes (eq 6).12
9-Anthraquinone is converted into 10-chloro-9-anthracenecarbaldehyde (eq 7).13 However, few examples of the synthesis of b-chlorovinyl aldehydes14 using MFA-POCl3 have been reported.15
Numerous cyclizations have been reported when DMF-POCl3 is used as the reagent, but few have been reported using MFA-POCl3.16 Hippuric acid is converted into a substituted isoxazole by the action of MFA-POCl3 (eq 8).17 An allylbenzene has been reported to give a dihydronaphthaldehyde (eq 9).18
Although the use of MFA-POCl3 in Vilsmeier reactions has been largely replaced by adducts formed from DMF-POCl3 (see Dimethylchloromethyleneammonium Chloride), MFA-POCl3 often gives aldehydes in higher yield and at lower temperatures than required for reactions with DMF-POCl3.1a,19 MFA-POCl3 is considered to be more reactive,19 but extensive decomposition occurs at high reaction temperatures. The cost and low molecular weight favors the use of DMF-POCl3.1a,19
Paul R. Giles & Charles M. Marson
University of Sheffield, UK