I would like to rise the question of preparation of 2,5-dimethoxybenzaldehyde from hydroquinone again. It was discussed a month ago in „2C-X 'cursors from hydroquinon" thread and commented by Rh. and Os.
We all know the JCS Perkin I, 1980, 1862 article, witch describes the reaction of phenol (1,0 mol), SnCl4 (0,1 mol), Bu3N (0,4 mol) and paraformaldehyde (2,2 mol) in toluene (typo in original article, 200 ml should be 2000 ml) under nitrogen atmosphere and heating at 100°C for 8 h.
Patent US4151201
by the same author teaches this reaction to be performed with SnCl2 or SnCl4, 3 mol paraformaldehyde and reflux temperature (up to 110°C, 8h). Yield for 2,5-dihydroxybenzaldehyde is given 48%.
A new variation of this formylation reaction for production of 3-substituated salicylaldehyde derivatives is described in
Patent US6080895
by Japanese authors, claiming yields of at least 95% !
This improved process comprises in first stage heating the phenol (1,0 mol), SnCl4 or SnCl2 (0,1 mol), a base (2,6-lutidine, Bu3N, Et3N etc., 0,92 mol) and paraformaldehyde (2,2 mol) in toluene (2160 ml) at 60-85°C until achieving conversion of 30 to 80% and then completing the reaction at 95-105°C (aprox. 10 hours).
For 2-hydroxy-3-methylbenzaldehyde from o-cresol 99% yield and 99% selectivity is given when the reaction is carried out at 80°C for 5h (1st stage) and then at 100°C for 10 h (2nd stage). However, the yield and selectivity drop to 42% and 75% respectively, when the reaction conditions are altered to 40°C for 7h (1st stage) and then at 95°C for 13 h (2nd stage).
But, when really performing this reaction with hydroquinone, that is almost completely insoluble in toluene and, even with careful heating in an oil bath and strong overhead stirring, the entire reaction mass will polymerise already at 70°C, yielding beautiful resin and only a trace amount of 2,5-DMB. It is obvious that proper reaction conditions are essential to avoid thermal degradation and polymerisation of hydroquinone.
Can anybody report a better experience with this reaction?