scarmani (Hive Bee / Eraser)
03-12-03 01:36
No 416080
      2C-E from 2,5 dimethoxybenzaldehyde?  Bookmark   

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 ...  Bookmark   

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/chemistry /25-dimethoxyacetophenone.html