IudexK2 (Hive Bee)
10-26-01 18:04
No 229058
      Sulfuric acid in LAH reductions  Bookmark   

In PiHKAL, Shulgin frequently adds conc. H2SO4 to LAH/THF before adding the nitrostyrene... can somebee explain to me how this works and if it is a good/necessary thing to do or not?

Example:
A solution of 2.0g LAH in 100mL anhydrous THF under He was cooled to 0C and vigorously stirred. There was added, dropwise, 1.3mL of 100% H2SO4, followed by the dropwise addition of a solution of 3.1g 3,4-dimethoxy-5-ethoxy-beta-nitrostyrene in 50mL anhydrous THF, over the course of 10 min. The mixture was stirred at 0C for a while, and then brought to a reflux on the steam bath for 30 min. After cooling again, the excess hydride was destroyed with IPA in THF, followed by the addition of 20mL 10% NaOH which was sufficient to convert the solids to a white and granular form. These were removed by filtration, the filter cake washed with IPA, the mother liquor and filtrates combined, and the solvents removed under vacuum. The residue was added to 150mL dilute H2SO4, and the cloudy suspension washed with 2x 75mL CH2Cl2 which removed much of the color. The aqueous phase was made basic with 25% NaOH, and extracted with 3x 50mL CH2Cl2. The solvent was removed from these pooled extracts and the residue distilled at 103-116C at 0.25 mm/Hg to provide 2.3g of a colorless viscous liquid. This was dissolved in 10mL IPA, neutralized with about 25 drops of concentrated HCl, which produced an insoluble white solid. This was diluted with 40mL anhydrous Et2O added slowly with continuous stirring. The white crystalline 3,4-dimethoxy-5-ethoxyphenethylamine hydrochloride was isolated by filtration, washed with Et2O, and air dried, and weighed 2.4g. It had a mp of 202-203 C which increased by one degree upon recrystallization from boiling IPA.

Many thankx,
IudexK
 
 
 
 
    Rhodium
(Chief Bee)
10-26-01 18:23
No 229064
      Re: Sulfuric acid in LAH reductions  Bookmark   

2 LiAlH4 + H2SO4 => 2 AlH3 + Li2SO4 + 2 H2

AlH3 is a reducing agent with milder reducing properties than LiAlH4.
 
 
 
 
    IudexK2
(Hive Bee)
10-26-01 18:40
No 229068
      Re: Sulfuric acid in LAH reductions  Bookmark   

Ahhhhhhhhhhhhh I see. Thankx. Is AlH3 generally a better reducing agent for nitrostyrenes, or is it dependant on the nitrostyrene in particular?
 
 
 
 
    Rhodium
(Chief Bee)
10-26-01 18:45
No 229070
      Re: Sulfuric acid in LAH reductions  Bookmark   

I don't know really. Tabulate the Pihkal yields for all Shulgin's AlH3 reductions and see if the yields are generally better than the ones using LiAlH4.
 
 
 
 
    megamole
(Hive Bee)
10-26-01 21:22
No 229105
      Re: Sulfuric acid in LAH reductions  Bookmark   

The reason for treating LAH with sulfuric acid is that it generates alane, AlH3, which in the presence of THF or ether, is not as strong of a Lewis acid. While LAH can remove aromatic halogens and a great deal more functional groups, alane will not. In cases where a greater degree of a certain selectivity is needed, alane is far superior.

Speaking of which, are there any people here with practical experience working with in-situ generated alane and borane complexes? There are so damn many facinating practical applications of these materials, but there has been such little discussion on the subject (and even fewer experimental results) here at the Hive. We need to resolve this!
 
 
 
 
    yellium
(Hive Bee)
10-27-01 01:22
No 229161
      Re: Sulfuric acid in LAH reductions  Bookmark   

I've been informed that alane reductions work. And you don't need 100% H2SO4, 96--98% also works.
 
 
 
 
    IudexK2
(Hive Bee)
10-27-01 02:15
No 229165
      Re: Sulfuric acid in LAH reductions  Bookmark   

Or anhydrous AlCl3.