Phenol methylation with Betaine1from Lego, HTML by metanoid
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Various phenols are transformed into the corresponding phenol methyl ethers (methoxy derivates) with betaine (trimethylglycine, trimethylammoniumacetate, carboxy-N,N,N-trimethylmethanaminium) in presence of CaO.
The phenol (0.05-0.1 mole) is mixed with an equimolar amount of betaine (anhydrous) and CaO (50 mole%) in a round-bottomed flask equipped with a destillation unit. The reaction mixture is slowly heated with an oilbath. Below 200°C the mixture becomes clear and an increasing gas evolution indicates beginning of the reaction.
The formed ether passes over during the reaction.
Polysubstituted ethers with higher boling points are extracted several times with Et2O from the residue in the flask and treated as described.
The byproducts of the reaction are the corresponding phenoxy-aceticacids and trimethylamine. (CAUTION: noxious gas, soluble in EtOH, H2O; should be trapped in an acid solution).
Betaine hydrochloride and betaine dihydrogencitrate are OTC prescription-free medicaments (at least in the neighbour country of the authors) against liver diseases. 1 g betaine costs about ~1 US-$ as medication.
1 kg of betaine hydrochloride cost about 50 US-$ from a well-known chem supplier. Betaine is for 4times cheaper than MeI, but twice as expensive as DMS ($/mole).
Preparation of betaine (anhydrous) from betaine hydrochlorid should be done analogous to the preparation of hydroxylamin from hydroxylammonium chloride/sulfate. Dissolve in MeOH, treat with K2CO3, filter and evaporated MeOH. Last step might be skipped because heatin the reaction mixture as described above will get rid of MeOH.
Preparation via or from hydrochloride2
Quite useless, betaine hydrochloride is heated with H2SO4and then treated with a Ba-salt to precipitate the BaSO4.
Although the authors didn't perform any experiments with polyphenols (e.g. hydroquinone, 2,5-dihydroxybenzaldehyde, 3,4,5-trihydroxybenzaldeyhde), one could expect similar results as even sterical hindered phenols react in good yields.
Benzoic acid was converted to benzoic acid methyl ester in 50% yield without CaO. Aliphatic alcohols didn't react until octanole, 1-methoxyoctan was prepared after 10 h reflux in 5% yield.
No other bases are mentioned by the authors. Perhaps K2CO3 or NaOH work, too.
Methylation with betaine is OTC, non-carcinogenic, requires no special equipment, proceeds fast, yields are moderate to high and work-up is easy.
 Monatshefte für Chemie (1966), 97(4), 1207-16.