LAH reduction ?

[Noid]

When reducing the amide with LAH, is it necessary to perform the rxn under nitrogen? I ask this out of confusion. On Rhodiums site, the IAA -> DMT writeup has 2 synths on reducing the amide to dmt. One of them calls for nitrogen and allowing the rxn to stir for 40 hours.

"To a stirred suspension of LiAlH4 (0.4 g, 10.5 mmol) in dry THF (15 ml), the amide 2 (0.4 g, 1.98 mmol) dissolved in dry dichloromethane (25 ml) was added slowly. The mixture was stirred for 48 hrs at room temperature under nitrogen...."

The other, not nearly as detailed, reads:

"A suspension of finally-divided amide (2.1 g) in 100 ml of ether was added to a slurry of 0.8 g of LiAlH4 in 50 ml of ether, and the mixt refluxed for 4 hrs. The mixt. was treated in the usual way, and the final org. extract of amine gave after recryst. from hexane 1.6 g (85%) of material mp 47-49°C."

I am curious as to why it is needed. What purpose does it serve?

Also, is it just me or is there very little in the FSE on this method.. is it just that easy that no one needs to ask questions? Sounds to me like a detailed writeup is in order, complete with juicy pictures  

Thanks

[freakyDMT]

Your reactionflask has to be purged with N2 because LAH reacts with moisture and O2 out of the air which fucks up
your LAH making it inactive.

[Xicori]

inert athmosphere isnt absolutely necessary for LAH reductions, but it is a safety factor...

user dry solvents and drying tubes - thats enough, especially on small batches.... but i wouldnt like to make a rnx with 100gs of LAH without inert athmosphere

bee careful!

[Rhodium]

It is not as troubling to work with LAH as FreakyDMT makes it look like, atmospheric oxygen is not a problem when you are working with LAH amounts between ~2-20 grams - below and above that I would reccommend to use a slow nitrogen or argon flow through your flask.

However, as suggested by Xicori, you really should make use of drying tubes filled with anhydrous CaCl₂ to keep atmospheric moisture out, as well as using rigorously dried solvents with max 0.05% water, or your yields will drop (as well as the reaction between LAH and water might pose a fire hazard!).

[Noid]

I really appreciate everyones responses. Maybe all the drama surrounding LAH reductions isn't necessary as long as the precautions stated in this thread are taken.

Swim plans on drying his solvent to the fifth power, then run a 1g LAH reduction as his first.. all the while clutching a dry powder fire extinguisher!  

A good alternative to DMT without the use of LAH was brought to my attention

Post 451545

(Chimimanie: "Thanks", Tryptamine Chemistry)

Is it possible to go from IAA, back to plain ol' indole?

[Rhodium]

Is it possible to go from IAA, back to plain ol' indole?

I am sure that many chemists would be interested in a gram-for-gram exchange, but there is no chemical method of value. I know vacuum pyrolysis would yield some indole, but unfortunately mostly skatole (3-methylindole).

[yellium]

You might also consider doing your reduction with alane (conveniently prepared from LAH by dropping a small amount of conc H2SO4 in your LAH using a micropippette.)

IIRC, alane yields better results than LAH when reducing certain compounds, and I thought indole-like compounds were among those. I don't know that for sure though.

[Vaaguh]

In case you do decide to use an inert atmosphere, which isnt really necessary for lah reductions indeed i'd suggest you use argon as argon is relativeley easy obtainable.

My favorite way is by putting the upper piece of a gas washflask on top of a reflux condenser and letting a slow stream of argon flow in, because the argon is heavier then air it will push the air out.