03-04-03 08:59
No 413718
      R-NH2 --> R-N(CH3)2 reference.
(Rated as: excellent)

(a) Preparation of N,N-dimethyl-(+)-neomenthylamine    methiodide from N,N-dimethyl-(+)-neomenthylamine:

A mixture of 14.3 gm (0.1 mole) of (+)-neomethylamine, 25.2 gm (0.3 mole) of sodium carbonate, 42.6 gm (0.3 mole) of CH3I, and 150 ml of CH3OH are heated under reflux with vigorous stirring for 75 hours.  After 24 and 48 hours additional portions of methyl iodide are added until a total of approximately 65 gm (0.45 mole) of methyl iodide has been used.  The reaction mixture is then evaporated to dryness under reduced pressure using a rotovap.  The residual solid is extracted 3x with 150 ml portions of boiling chloroform.  The combined extracts are cooled, filtered, and evaporated to dryness.  The residual crude methiodide is recrystallized once from a mixture of acetone and pentane with a yield of 28.2 gm (90% of theory).

(b) Reduction of quaternary ammonium salts:

In a 3-necked flask fitted with an efficient relux condenser, toppped by a drying tube, magnetic stirrer, and electric heating mantle, is placed 175 ml of freshly distilled, anhydrous THF.  To the solvent is added, with caution, 7.8 gm (0.2 mole) of powdered LAH.  The mixture is heated under reflux for 1 hour.  Then 11.7 gm (0.04 mole) of the product from (a) in finely ground form is introduced in a single portion and the mixture is heated under reflux with stirring until the evolution of methane has ceased.  The reaction mixture is then cooled and cautiously hydrolyzed by the gradual addtion of 20 ml water.  To isolate the product, 100 ml ether is added and the mixture is refluxed for 2 hours.  After cooling, the solid is separated by filtration and the filter cake is washed repeatedly with ether.  The filtrate and the washings are concentrated by distillation.  The residue is washed with five 50 ml portions of water to remove any residual THF and the remaining organic material is dissolved in pentane.  The pentane solution is extracted with two 45 ml portions of 2N HCl and two 25 ml portions of water.  The aqueous acidic washings are combinded and heated with a solution of 10 gm NaOH in 50 ml water.  The amine is separated by layering pentane over the water and the aqueous layer is repeatedly extracted with pentane.  The combined extracts are dried over MgSO4.  After removal of the solvent by distillation, the residue is distilled through a semi-micro vacuum distillation column.  Yield 4.9 gm of N,N-dimethyl-(+)-neomenthylamine (75% of theory), b.p. 75 to 76 degrees C @ 4.5 mm Hg pressure.

The above has obvious potential appplications to tryptamine.

(1) Decarboxylation of amino acids:

Amino acids are decarboxylated @ 150 degrees Celsius using phenyl-CO-CH3 under N2(g) followed by acid hydrolysis with HCl of the R-N=C-etc.  See G. Chatelus, _Compt. Rend. 248_, 1588 (1961); _254_, 136 (1962).

Nothing new here really, I suppose.