Writeup on the production of 4-methyl-2,5-dimethoxy-chloromethyl-benzene:
The following was made using Chimimanie's procedure: Synthesis of 2-Chloromethyl-5-alkyl-DMB
Using 15 grammes of the prepared 2,5-dimethoxytoluene, a chloromethylation was attemped as described by the following:
Using a hydrogenchloride generator made with HCl(aq) dripped into sulfuric acid, gaseous hydrogen chloride was bubbled into a well-stirred mixture of 20ml of 37% commercial formaldehyde stabilized with 15% methanol, 10 ml of 30% hydrochloric acid and 40 ml of dioxane for 15 min. The temperature was limited by the refluxing of the dioxane. To this mixture 15,2g (0.1 mole) of home made 2,5 dimethoxytoluene was added, dropwise, over a period of 5 min, while the temperature was maintened between 55-60°.
When the addition was completed, the passage of hydrogen chloride maintained for an additional couple of minutes. The mixture was cooled and poured into 0,2 L of ice water and 50 mL's DCM. The aqueous layer was extracted twice more with 50 mL's of DCM. The combined DCM extracts were washed with cold water until the washings were neutral to litmus. Only two water washes was needed to accomplish this. The DCM was yellow in color.
The DCM was removed on an oil bath and the residue was distilled directly under reduced pressure. The temperature of the oil bath reached 210 degrees celc. before the product came over. The gas temperature was 160-165 degrees. The original patent used a vigourex column, but the oil was so viscious than the column was omitted. The distillated soldified somewhat in the condensor. Only 50% of the original "goo" could be distillated. The condensor was rinsed with ether to pull the clog into the reciever.
The flask which was distilled from was full of poly/dimerized crap. I think the temperature in the oild bath was too high for the distillation. Either a better vacuum pump is to be used next time or the distillation should be omitted and directly used for either a sommelet or NaCN swap.
The product crystallized very nicely upon standing in the flask. It consisted of crystals, resembling 2,5-dimethoxybenzaldehyde, with a slightly yellow tint. No yeild has been evaluated yet, but i will post it once it has been measured.
This is a very nice and quite OTC way of preparing 4-methyl-2,5-dimethoxychloromethylbenzene. The yeild could be improved somewhat, but the reaction works nice and fast. It should be mentioned that the chloromethylation reactants are very toxic(as rumored by Hest), and every possible protection was used.
The title compound will be subjected to a Sommelet, to give 4-methyl-2,5-dimethoxy-benzaldehyde. A writeup of this reaction will follow soon.
Cheers
Bandil