Nenitzescu synthesis

Extensions of the Nenitzescu synthesis to A-acyl- or JV-sulfonyl-quinoneimines affords 5-aminoindoles (equation 110) (58JA3291). 

Patrick, J. B., Saunders, E. K. Studies on the Nenitzescu synthesis of 5-hydroxyindoles. Tetrahedron Lett. 1979, 4009-4012. 

In the Nenitzescu synthesis of 5-hydroxyindoles, an A-aryl substituted amino-propenoic ester may be used, albeit with a low yield of product [2343]. Better yields may be obtained by reacting the quinone at ambient temperature with an enaminonitrile [3246]. The methylthio group may be removed by heating with Raney nickel. Magnesium methyl carbonate is sometimes used to carboxylate a methyl ketone but when it is warmed with the methyl ketone (35.3), it causes cyclization of the keto side-chain [2747]. A dioxopyrimidine aldehyde (35.4) is cyclized in moderate yield by heating with carbonate in DMF [2668]. 

The Nenitzescu synthesis " is another process about which some of the mechanistic details remain unclear, but which can be used for the efficient synthesis of certain 5-hydroxy-indoles. ... 

Only a few indole syntheses make use of building blocks in which the N-atom is not directly bonded to an arene. The Nenitzescu synthesis is of this type. In this synthesis, 1,4-quinones are condensed with 3-aminoacrylic esters to give 5-hydroxyindole-3-carboxylic esters 44. The mechanism of this synthesis has not been completely clarified. It includes a Michael addition (-> 41) and a cyclodehydration (42 43) as well as a redox transformation (41 42 and 43 44) [53] ... 

Indoles are obtained by specific cyclizations (Fischer synthesis, Reissert synthesis, Batcho-Leimgruber synthesis, Nenitzescu synthesis), as are carbazoles from biphenylene or diphenyl-amines and pyrrolidines (Hofmann-Loffler reaction). 

Other references related to the Nenitzescu synthesis are cited in the literature. 

This reaction was first reported by Nenitzescu in 1929. It is the synthesis of a 5-hydroxyindoie derivative involving the condensation between a 1,4-benzoquinone and a /3-amino-a ,/3-unsaturated compound and subsequent cyclization. Therefore, this reaction is generally known as the Nenitzescu indole synthesis, Nenitzescu reaction, j or Nenitzescu synthesis.Occasionally, it is also referred to as the Nenitzescu cyclization, Nenitzescu condensation, s.2i qj. Nenitzescu process. It should be pointed out that the synthesized indole derivatives by this reaction are restricted to those with an electron-withdrawing group at position 3, such as an ester or a carbonyl group. In addition, the completion of this reaction requires an appropriate oxidizing agent to convert the initial adduct into the indole derivative. i From monosubstituted quinone, 4-, 6- and 7-substituted 5-hydroxyindole derivatives all are possible products, but 6-substituted isomer is the one normally obtained. ... 

Nenitzescu (see Darzens-Nenitzescu Synthesis of Ketones) Nenitzescu Indole Synthesis Nenitzescu Reductive Acylation Nicholas Reaction... 

Neber rearrangement 31 Nenitzescu synthesis (indole) 144 Niementowski synthesis (quinazoline) 495... 

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