03-12-03 01:36
No 416080
Doing some preliminary research on the synthesis of 2C-E; UTFSE yielded Shulgin's synth, Post 41646 (psyloxy: "Re: 2,5-Dimethoxybenzaldehyde Hey, OS, Bekr, Mistr", Chemistry Discourse), Post 60192 (yellium: "Another route to 2C-[BDE]", Chemistry Discourse), Post 263890 (poix: "alkylation of quinones", Novel Discourse), Post 404204 (psygn: "2C-H ---> 2C-E", Chemistry Discourse).
So if I understand Shulgin's synth, he starts with p-dimethoxy benzene, puts a methyl ketone in what becomes the 4 position, and then turns that into an ethyl (in a reaction that sounds messy and has a poor yield).
Then he puts an aldehyde in the 1 position, converts the molecule into the beta nitrostyrene with nitromethane and ammonium acetate, and reduces that with LAH to get 2C-E.
It strikes me that Shulgin first puts the ethyl group in, and only then makes the aldehyde. Can one start with 2,5 dimethoxybenzaldehyde and then put an ethyl group in the 4 position (without protecting the aldehyde group)?
From a couple of the abovementioned posts, it seems like BuLi is a reagent that allows selective alkylation with alkyl halides. Could it be of use ethylating the dimethoxybenzaldehyde at only the 4 position?
If not, how could it be used with 2C-H to get 2C-E. Would one have to go through 2C-B first?
Sorry if my questions are naive; I am just starting to learn organic chemistry, all comments welcome.
stop, drop & roll
(Chief Bee)
03-12-03 13:50
No 416265
You cannot use BuLi with an unprotected benzaldehyde, as it would polymerize (the aldehyde group acting as electrophile, just as alkyl halides do, but making an alcohol instead of a hydrocarbon).
You could start with 2C-H, protect the nitrogen, lithiate in the 4-position with BuLi, add EtI, quench and deprotect the nitrogen, but that roundabout way would probably be much more wasteful than ethylating earlier in the synthesis.
You can reduce 2,5-dimethoxyacetophenone to 2,5-dimethoxyethylbenzene with Zn/Hg and HCl in 50% yield too, see JOC 25, 1245 (1960). 2,5-dimethoxyacetophenone is made from 2,5-dihydroxyacetophenone, see ../rhodium /25-dime