Methylenation of Catechols. General Procedure.in DMF
To a mechanically stirred degassed suspension of catechol (53,9mmol) and Cs2CO3 (80 mmol) in anh. DMF (130ml) was added BrCH2Cl (5.26ml, 80.9mmol) and the resulting mixture was heated to 110°C After 2h, the reaction was cooled to room temp. and filtered through a pad of celite with EtOAc washing. The filtrate was concentrated almost to dryness and the residue diluted with water and extracted with EtOAc (3x). The extracts were combined, washed with dH2O, brine, dried over anh. MgSO4, filtered and concentrated.
in MeCN
To a mechanically stirred degassed mixture of catechol (21.9mmol) and Cs2CO3 (10.7g 32.9mmol) in MeCN (55ml) was added BrCH2Cl (2.13ml 32.9mmol) and the resulting suspension was heated to reflux. After 5h, the reaction was cooled to RT and filtered through a pad of celite with EtOAc washing. The filtrate was concentrated and directly chromatographed on silica gel to provide product.
Yield of piperonal from protocatechualdehyde was 89% either in DMF (2h) or MeCN (8h).
Cs2CO3 is absolutely harmless, but not the cheapest carbonate on earth. Maybe one can get some Kg cheaply from waste metal recycling co's, you'll find a couple that sell it. Proportions for an upscaled version would be 100g 3,4-diHO-benzaldehyde, 388g Cs2CO3 and 2,5L MeCN though I guess you don't need as much solvent.
I don't get why they use BrCH2Cl here instead of CH2Br2. But it's prep. from DCM can be found in
Patent US2553518
Ref: Zelle, Robert E.; McClellan, William J.;
Tetrahedron Letters 32(22) 2461-2464 (1991)
(
https://www.thevespiary.org/rhodium/Rhodium/chemistry/methylenation.aprotic.html)
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