Stoichiometric reduction with low valent sulfur (sulfide/dithionite)

Mechanism + Description

A number of inorganic sulfur reagents can be used to reduce aliphatic and aromatic nitro compounds to amines such as sodium sulfide, sodium hydrogen sulfide and sodium dithionite. Mechanism is via electron transfer – shown for dithionite.

General comments

Reagents are heated with nitro compound. Ethanol-water is a common solvent system.

 

Key references

Tetrahedron Lett. 1988, 29, 635  Sodium sulfide has been used for the selective reduction of aromatic nitro group in the presence of aliphatic nitro groups
J. Med. Chem. 2005, 48, 5104  and  J. Med. Chem. 2007, 50, 4453 reduction of nitro aromatics with sodium dithionite
Chemistry Letters 2008, 37 (5), 544 and J. Med. Chem. 2009, 52, 1275  reduction of nitroarenes with hydrogen sulfide salts

 

Relevant scale up example

Imidazole formation following reduction  with Na2S2O4 Gram scale Na2S2O4  process safety information given
Org. Process Res. Dev. 2012, 16, 96

 

Green Review

  1. Atom efficiency (by-products Mwt)
    Overall moderate -  Dependent on sulfur salt used. High Mwt. of many S salts is due to polyhydrate formation.
  2. Safety Concerns
    Use of sulfur compounds can give rise to issues with odour and toxic gases (H2S) if treated with acids. Dithionite is unstable and it’s decomposition temperature can be considerably lowered in contact with organic solvents.
  3. Toxicity and environmental/aquatic impact
    These sulfur reagents are of concern in fresh water ecosystems. Even low levels can give rise to odor issues.
  4. Cost, availability & sustainable feedstocks
    Generally readily available and cheap.
  5. Sustainable implications
    None.
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