amide reduction

[rev drone]

While tryptophan is an inexpensive starting material for tryptamine synthesis, it is by no means the only one. When DMT World was still around, some discussed the possibility of condensing indole acetic acid with an amine, to form a sort of "tryptamide". This would then be reduced to the desired tryptamine.

Now amide reduction can be accomplished with LiAlH4, as well as catalytic hydrogenation, but what other practical methods exist out there?

------------------
-the good reverend drone

Ipsa scientia potestas est

[Rhodium]

Perhaps Al/Hg? I have noticed that benzoic acids can be reductively aminated with at least primary amines using Al/Hg. It could work work with IAA too.

[Strontium]

Ehem!

Dare I say Red-Al...
According to the litterature it reduces amides quite nicely.

Strontium

[IronMonkey]

Amides take quite a beating to reduce, even with IAA, I think it might lead to significant ring reduction if performed with H2!  But it is definitely an attractie alternative if NaCNBH3 does get put on lockdown as rev seemed to indicate it would be soon.

[Crankenstein]

This has been discussed at the Hive before.  According to Jerry March in Advanced Organic Chemistry, amides can be reduced to amines with sodium in an ethanol solvent.

[Strontium]

In TIHKAL the good Doctor uses Red-Al quite a few times to reduce amides to amines.
Quick and easy reductions, no 24-fucking- hours refluxing(God I hate that).

Strontium

[hest]

I've eksperience with LiAlH4, boil in ether for 24 H. Works ok.
Recryst. from acetonitrile
Take care (DMT is a strong one)

[hest]

By the way, make a fast recryst. The hot solution goes from clear to brown fast.

[Osmium]

Benzylamine from benzylamide - is this applicable to other amides?

To a stirred suspension of NaBH4 (1.89g, 50mmol) and benzamide (1.21g, 10mmol) in dioxane (20ml) is added acetic acid (3.0g, 50mmol) in dioxane (10ml) over a period of 10 minutes at 10°C; the reaction is stirred at reflux for 2hrs. The mixture is concentrated to dryness in vacuo, excess reagent is decomposed with H2O and the solution extracted with CHCl3. The extract is washed with H2O, dried over Na2SO4, gassed with HCl and evaporated to dryness and the residue recrystallised from MeOH/Et2O to give benzylamine hydrochloride (1.09g, 76%).

[Osmium]

General procedure for the reduction of amides with NaBH4/methanesulphonic acid in DMSO

To a 2-neck 100ml flask are added 16mmol of amide, 1.61g (40mmol9 of NaBH4 and 20ml of DMSO. Methanesulphonic acid (3.4ml, 55mmol) and 20ml DMSO are mixed and added dropwise over a 30 minute period. Gas is evolved and a gelatinous substance is formed, which dissolves when the acid comes to exceed the NaBH4 on a molar basis. If the reduction is to produce a prim. or sec. amine, the reduction is quenched by the addition of 20ml of 10% NaOH. In the case of a tert amine the reaction is kept at 70°C for 2 hrs to liberate the product from the borane complex. Isolation then proceeds in the same way as for prim. and sec. amines. After the quench the product is extracted with 3*10ml DCM, washed with 3*10ml 0.1M NaOH to remove the DMSO, and the product is extracted into 3*10ml 10% HCl. Neutralisation with 10% NaOH is followed by extraction of the product with 3*10ml DCM, drying over CaSO4 and fractional distillation.
hexanamide ---> hexylamine 74%
acetanilide ---> N-ethylanilide 77%
N,N-dimethylbenzamide ---> N,N-dimethylbenzylamine 59%

Both procedures from Vogel, 5th ed., p774

[hest]

BH3 is also a solution (from NaBH4 and I2 or H2SO4 or BF3 aso.)
But I think that LiAlH4 is more easy to work with.
The routhe from indol, oxalylchlorid and DMA is also a solution.

[psyloxy]

Sorry for being ignorant but what is red-Al ?
P4/Al ?

--psyloxy--

[Acme]

Red-Al is a 65+ wt. % solution of sodium bis(2-methoxyethoxy) aluminum hydride in toluene