06-16-04 21:10
No 513815
Here's another mod to the traditional meth grignard.
We start with benzyl chloride, N-methyl carbamate, and acetaldehyde or acetaldehyde diethyl acetal (produced by the method of Post 513668 (ning: "Bleach + EtOH --> Acetaldehyde", Chemistry Discourse)).
Ethyl N-methyl carbamate is produced easily and in high yields by hofmann rearrangement of acetamide in ethanol, and is very useful for many purposes (for example: Post 503311 (ning: "bromosafrole to MDMA via N-methyl carbamates", Novel Discourse)).
With acetaldehyde diethyl acetal, just heating together with ethyl N-methyl carbamate should be enough to produce ethyl N-alpha-ethoxyethyl N-methyl carbamate.
Alternately, the procedure of japanese patent JP8268991 is followed with ethyl N-methyl carbamate, acetaldehyde, and ethanol in acidic solution. (90% yield quoted)
This material is dried, the alcohol evaporated and the product dissolved in ether and dried over mol. sieves (necessary?)
The organometallic reaction is following the vague directions of Tet. Let. 1989, 5611 "The alkylation of a-ethoxycarbamates with organo-lead, -zinc, and -copper reagents. High Cram selectivity and formal nonbasic alkylation of imines"
Benzyl chloride is dissolved in ether or THF and dry zinc powder added with stirring. Extra ZnCl2, FeCl2, or AlCl3 could be added here.
The solution is cooled (in the paper to -78 C, but is that really necessary?), the alpha-ethoxy carbamate added slowly, and the solution allowed to rise to 0 C or RT (depends?), then quenched with NaHCO3 solution. {I would use HCl...}
Expected yield: ~70 - 88%
The amine is deprotected by stirring the crude product with 1 M HCl solution, the solution filtered and the amine salt purified by A/B extraction and gassed to a salt.
The reaction looks like this:
Molecule: formation of first group ("CNC(=O)OCC.CC(OCC)OCC>>CN(C(OCC)
Molecule: organometallic addition ("c1ccccc1CCl.CN(C(OCC)C)C(=O)OCC>>
I guess it's sorta kinda like the reformatskii reaction...
The lewis acid is an essential part of the reaction. I would prefer just the ZnCl2 generated by the production of the zinc alkyl be the alkylating reagent, but in the paper they use TiCl4 (and BF3.Et2O once) instead. I'm sure the hive brain trust can find out what lewis acids work well enough.
In any case, the yields probably end-to-end would be around 50-60%, and the method avoids any need to deal with the annoying methylamine base or acetaldehyde directly. Also, the difficult acetaldehyde methylimine formation is avoided completely.
Also, of course, we can use zinc. From batteries? You decide
Clandestine chemist // amateur pharmacologist
