Experiments on the Orientation of Substituted Catechol Ethers
Jones & Robinson
J. Chem. Soc. 921 (1917)
5-Bromoveratraldehyde
This substance has been previously prepared by Dakin (Amer. Chem. J., 1909, 42, 494) by the methylation of 5-bromovanillin with methyl sulphate and potassium hydroxide, and also by Pschorr, Selle, Koch, Stoof, and Treidel (Annalen, 1912, 391, 31) by a similar process applied to the product of bromination of protocatechualdehyde, but these authors give no details of the process employed. Our experiences in this connexion indicate a precaution which it is desirable to take in methylating phenolic aldehydes.
Vanillin was brominated in acetic acid by means of rather more than a molecular proportion of bromine, and the aldehyde was then methylated by methyl sulphate and potassium hydroxide in alcoholic solution. The operation was not entirely satisfactory owing to the readiness with which the aldehyde undergoes the Cannizzaro reaction, and no more than a 50 per cent yield could be obtained. The conditions were similar to those which gave good results in the preparation of veratraldehyde (Perkin and Robinson, T., 1907, 91, 1079), but for the reason mentioned the solution should never be allowed to become very strongly alkaline. On the addition of water, an oil separated, and usually slowly crystallised when the mixture was kept in a cold place. Occasionally, however, the oil could net be solidified, and was dissolved in ether and the aldehyde extracted by a solution of sodium hydrogen sulphite, from which it was regenerated as a readily crystallising oil by the addition of sodium carbonate. The substance was collected and dried and crystallised from light petroleum, from which it separated in felted needles melting at 62°C.
On acidifying the alkaline solution from which the aldehyde was originally separated, a crystalline precipitate was obtained, and this was identified as 5-bromoveratric acid. The substance crystallised from water in needles melting at 191°C, and the silver salt was prepared. The ethereal solution from which the aldehyde had been extracted by repeated washing with sodium hydrogen sulphite was dried and evaporated, and a yellow oil remained; this could not be crystallised, but was readily converted into a solid nitro-derivative by the action of nitric acid in acetic acid solution in the cold. The substance crystallised from alcohol in pale yellow, slender, brittle needles melting at 115°C. This substance does not show the properties of a nitrobenzyl alcohol, and is unchanged after treatment with acetyl chloride or with benzoyl chloride in the presence of pyridine. On oxidation with potassium permanganate in alkaline solution, it yields the bromonitroveratric acid which is mentioned in the next section. It may be synthesised in the following manner. 5-Bromoveratraldehyde dissolved in a little alcohol was added to a concentrated solution of potassium hydroxide, and the mixture well shaken from time to time during three days. The bromohomoveratryl alcohol was extracted with ether, and any unchanged aldehyde removed by shaking the solution with aqueous sodium hydrogen sulphite. The extract was then dried and evaporated and the residue warmed with concentrated aqueous hydrobromic acid. On the addition of water, a crystalline substance was obtained, which was collected and thoroughly dried and then added to a solution of sodium methoxide in absolute methyl alcohol. Sodium bromide separated, and after gently warming on the steam-bath during fifteen minutes the addition of water precipitated an oil, which was isolated and nitrated, and so converted into the substance which is under discussion This result demonstrates that the nitro-derivative is 6-bromo-5-nitro-4-methoxymethylveratrole. Not only has the aldehyde been converted by the action of the alkali into the corresponding alcohol, but the latter has been transformed into its methyl ether by the action of the methyl sulphate.
5-Bromoveratraldoxime
This derivative, obtained in the usual manner, crystallises from alcohol in needles melting at 85°C.