Guareschi reaction
The Guareschi reaction , or Guareschi Thorpe pyridine synthesis, is a name reaction in organic chemistry . It is used in the synthesis of pyridine - derivatives .
The reaction was first introduced in 1896 by the Italian chemist Icilio Guareschi (1847-1918) and expanded in 1911 by the English chemist Jocelyn Field Thorpe (1872-1940).
Overview reaction
During the synthesis, cyanoacetic acid (R 1 = H) or an ester (R 1 = alkyl) of cyanoacetic acid 1 reacts with an acetoacetic acid ester 2 . A pyridine derivative is obtained as the product:
The cyanoacetic acid amide can be reacted analogously with 2 to give the same reaction product.
Reaction mechanism
The mechanism is described in the literature and exemplified using the reaction of cyanoacetic acid with ethyl acetoacetate .
By adding ammonia , cyanoacetic acid is first enolized . The resulting intermediate product 3 forms a bond with the ethyl acetoacetate, with a rearrangement of a hydrogen atom . This creates intermediate stage 4 to which an ammonia molecule attaches in the next step. A further hydrogen and subsequent electron rearrangement finally leads to the splitting off of an ethanol molecule and the carboxamide 5 is formed. The next step is the ring closure. In the last two steps, further electron rearrangements split off two water molecules and the product obtained is the pyrirdine derivative 6 .
Individual evidence
- ↑ a b c Zerong Wang: Comprehensive Organic Name Reactions and Reagents , Wiley, 2010, ISBN 9780470638859 , pp. 1294-1297, doi: 10.1002 / 9780470638859 .
- ^ I. Guareschi: Accademici Residenti In: Memorie della Reale Accademia delle Scienze di Torino 48, 1896, p. 7.
- ^ FB Thole and JF Thorpe: The formation and reactions of iminocompounds In: Journal of the Chemical Society 99, 1911, p. 456, doi: 10.1039 / CT9119900422 .