The Henry Reaction

  The Henry reaction was first reported by Belgian chemist Louis Henry in 1895. The Henry reaction involves the addition of a nitronate salt to a carbonyl compound, usually an aldehyde. The reaction is also referred to as a Nitroaldol reaction. It is C-C bond-forming reaction used in organic synthesis.  

Mechanism:

  The Henry Reaction Mechanism can present in two steps    

1) Nitronate preparation

Nitronate is usually prepared in situ by treating the nitroalkane with a strong base, like hydroxide, alkoxide, or even an amine base.

2) Addition of Nitronate to aldehyde

  Next, an aldol reaction (C-alkylation of the nitroalkane) takes place with the carbonyl compound to form diastereomeric β-nitro alkoxides. Finally the β-nitro alkoxides are protonated to give the expected β-nitro alcohols. 

Double Henry Reaction:

In rare cases, the Henry reaction is even too favorable and can occur twice because the product is nitroalkane. This overreaction is encountered almost exclusively with formaldehyde; in these cases, a 2-nitro-1,3-diol is formed,  which can sometimes have synthetic value.

Henry Reaction Examples, Application

• The nitro group is quickly reduced to the amine; therefore, this is a route to 1,2-amino alcohols.
• The Henry product can also be easily dehydrated to a nitro-olefin, which is a Michael acceptor and can be reached at this position with several nucleophiles.  
• Especially synthesis of alpha-nitro ketone,   is a very versatile tool and is used  extensively by organic chemists.
• 1,2-Nitroalcohols are essential intermediates in organic synthesis.  

• An example of a tandem Henry plus Nef-reaction is the one-carbon homologation of pentoses to hexoses, meaning that carbon is added from a 5-carbon sugar to a 6-carbon sugar. 

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Stereoselective Henry Reaction :

  Henry’s reaction has been a prime target for diastereoselective and enantioselective synthesis. BINOL-metal catalysts,   best if derivatives of lanthanides, create a  chelated, rigid transition state for the reaction and therefore allow for excellent stereocontrol.  

Limitation :

• Henry’s reactions with ketones can be unsatisfactory or even impossible because the equilibrium lies in favor of the nitronate and the ketone.   
• Using aldehydes as reactants also brings the danger of base-promoted reactions like aldol condensations and Cannizzaro reactions of the aldehyde. These are the limitation of Henry’s reactions.

Related Reactions :

1. Aza-Henry Reaction
2. Nef Reaction

References :

• Henry, Louis (1895). Synthetic formation of nitrated alcohols
• ScienceDirect Henry-reaction
• Professor Dave Explains _ Henry reactions 
• Henry Reaction review