Erlenmeyer synthesis

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The Erlenmeyer synthesis is a name reaction in organic chemistry . It was named after the German chemist Emil Erlenmeyer jun. (1864–1921) and is a variant of the Perkin reaction . Azlactones can be synthesized by the Erlenmeyer synthesis by reacting aromatic aldehydes with an aromatic carboxylic acid (e.g. hippuric acid ) in the presence of acetic anhydride .

Overview of the Erlenmeyer reaction

The Erlenmeyer synthesis is also known by other names: Erlenmeyer-Plöchl reaction, Erlenmeyer-Plöchl synthesis and Erlenmeyer-Plöchl azlactone synthesis.

Reaction mechanism

The acetic anhydride initially attacks the oxygen atom of the hydroxyl group of the carboxylic acid 1 nucleophilically . Acetic acid is split off in the process. After a keto-enol tautomerism , compound 3 attacks the aromatic aldehyde again, so that compound 4 is formed. Under a dehydration and another tautomerism a place cyclization instead. Another acetic acid molecule is then split off and the desired azlactone 8 is obtained.

Mechanism of the Erlenmeyer reaction

Representation of α-keto acids

Then from Azlactones can be obtained by saponification α- keto acids produced:

Saponification of azlactone to α-keto acid

Representation of α-amino acids

If the C = C double bond is hydrogenated before saponification, α- amino acids are formed :

Representation of the α-amino acid

variants

If hydantoin or rhodanine are used instead of hippuric acid , the amino acids are obtained in higher yield.

A variant of the Erlenmeyer synthesis is the Erlenmeyer-Plöchl synthesis , which was named after the chemists Emil Erlenmeyer and Josef Plöchl (* 1853).

The synthesis describes chemical reactions in which glycine can be represented in a number of amino acids via oxazolinone and azlactone.

Mechanism of the Erlenmeyer-Plöchl synthesis

In the presence of acetic anhydride, hippuric acid self-condenses to form 2-phenyl oxazol -5-one. This intermediate product has two acidic protons and reacts with benzaldehyde , acetic anhydride and sodium acetate to form azlactone. This in turn can react by reduction to phenylalanine .

In a study, the Erlenmeyer amino acid synthesis was used as the core synthesis of L- m - tyrosine .

The benzyl ether of 3-hydroxy benzaldehyde reacts with 1 via the N -acetyl amide of glycine 2 , acetic anhydride and sodium acetate to form the azlactone (not shown in the synthesis route), which undergoes ring opening with sodium acetate in methanol to form the dehydroamino acid 3 . The subsequent hydrogenation gives the ( RS ) - N -acetyl- m -tyrosine methyl ester 4 (the benzyl ether group is split hydrogenolytically), a racemate. A special enzyme is able to cleave only the methyl ester of the ( S ) -enantiomer 5 , which is soluble in dichloromethane. What remains is the water-soluble ( R ) - 4 . The last step is the hydrochloric acid cleavage of the acetyl group from 5 , which yields ( S ) - m -tyrosine 6 .

Application of the Erlenmeyer-Plöchl synthesis

literature

Individual evidence

  1. ^ Z. Wang (Ed.): Comprehensive Organic Name Reactions and Reagents . Volume 1, Wiley, 2009, ISBN 978-0-471-70450-8 (3-Volume Set), p. 997.
  2. ↑ Josef Plöchl, professor in Kaiserslautern, born 1853. Edvard Hjelt: History of organic chemistry from the earliest times to the present, Vieweg 1916, person register.
  3. ↑ Plöchl J .: About some derivatives of benzoylimdocinnamic acid . In: Ber. . 17, 1884, p. 1623.
  4. ↑ Erlenmeyer, E. jun .: About the condensation of hippuric acid with phthalic anhydride and with benzaldehyde . In: Justus Liebig's Annals of Chemistry . 275, 1893, p. 3. doi : 10.1002 / jlac.18932750102 .
  5. ^ AW Ingersoll, SH Babcock: Hippuric acid In: Organic Syntheses . 12, 1932, p. 40, doi : 10.15227 / orgsyn.012.0040 ; Coll. Vol. 2, 1943, p. 328 ( PDF ).
  6. ↑ GE VandenBerg, JB Harrison, HE Carter, BJ Magerlein: 2-Phenyl-2-oxazolone In: Organic Syntheses . 47, 1967, p. 101, doi : 10.15227 / orgsyn.047.0101 ; Coll. Vol. 5, 1973, p. 946 ( PDF ).
  7. ↑ HB Gillespie, HR Snyder, RM Herbst, D. Shemin : dl-β-Phenylalanine In: Organic Syntheses . 19, 1939, p. 67, doi : 10.15227 / orgsyn.019.0067 ; Coll. Vol. 2, 1943, p. 489 ( PDF ).
  8. ↑ Cara E. Humphrey, Markus Furegati, Kurt Luly, Luigi La Vecchia, Thomas Leutert, J. Constanze D. Müller-Hartwieg, Markus Vögtle: Optimized Synthesis of lm-Tyrosine Suitable for Chemical Scale-Up. In: Organic Process Research & Development . 11, No. 6, 2007, pp. 1069-1075, doi: 10.1021 / op700093y .