LAH vs NaBH4

[Limpet Chicken]

In the TIHKAL synthesis of n,n-dialkyl tryptamines, is it absolutely essential that LAH must be used for the final reduction step to the finished tryptamine or can NaBH4 be substituted?

I do not intend to break any laws by synthesizing controlled substances of any sort, I just want to know if NaBH4 substitution is possible, and the method to calculate the amount of NaBH4, going from the documented quantity of LiAlH4.

Thanks.

 

[Dave]

Chances are it is.

Since LiAlH4 is so reactive, it is generally only used when necessary, and if NaBH4 is useable it is used. If you were to try using NaBH4 instead of LiAlH4, you would need the same number of moles since they each can donate up to 3 "H-" per molcule.

I'm not exactly familiar with the synthesis in question. Which functional group are you trying to reduce? I ask because NaBH4 will reduce some functional groups that LiAlH4 will, but not all of them.

 

[Limpet Chicken]

Of course, I am not about to put any illegal synthesis into practice, but the synthesis I was curious about was the n,n-DMT synthesis (and the other dialkyl tryptamines) from indole, via reduction of indol-3-yl N,N-dimethylglyoxylamide, and via Shulgin's route using ethyl formate.

 

[fastandbulbous]

Nope, sodium borohydride won't reduce amides to amines. Actually, I don't think any of the sodium-boron-hydrogen-whatever (eg sodium cyanoborohydride) compounds will reduce amides. So your stuck with lithium aluminium hydride, or hydrogen/metal catalysts (Raney nickel, palladium etc) to reduce amides (there are other exotic hydrides that might do the job, but can't name any off the top of my head).

Sodium borohydride will reduce aldehydes and ketones to primary and secondary alcohols respectivly, oximes and schiff bases to amines and a few other less demanding reductions, but for things like esters/carboxylic acids to alcohols, amides to amines and nitropropenes to amphetamines, you need the real nasty reducing agents

That's why drugs intelligence units monitor sales of LiAlH4 so closely, because a lot of synthetic routes to controlled drugs (esp the psychedelic amphetamines/phenethylamines *sigh* ) require something like LiAlH4 at some point, unless you want to do a much longer, and more involved synthesis

 

[Smyth]

Maybe you could write a new book: AIHKAL (A is for amide's).
It would be quite an easy book to write. Just follow grandpa Shulgin's syntheses bt substitute LAH for NaBH4. BTW, good luck on the taste tests

 

[ralf2]

NaBH4 / I2 or NaBH4 / H2SO4 kan reduce amides, but who know if it will work for this particular reaction. (Tryptamines can convert into quinolines in acidic enviroment.)

But even then, you have that ketone group to reduce as well.

 

[Dave]

It can, depending on the groups around it etc... but it will likely be SLOW. Shulgin knew what he was doing, stick with LiAlH4.

 

[Riemann Zeta]

LiBH4 is slightly less dangerous than LiAlH4, but still faster than NaBH4

 

[Limpet Chicken]

Speed is not really an issue, since this internet presence is a patiend one in the extreme, not to mention that the reaction would never be taking place, lithium hydrides of any sort are somwhat elusive these days, whilst their sodium counterparts are perhaps somewhat less frowned upon to be in the public domain