Erlenmeyer–Plöchl azlactone and amino-acid synthesis

The Erlenmeyer synthesis is a name reaction in organic chemistry. She was young after the German chemist Emil Erlenmeyer. named and is a variant of the Perkin reaction. The Erlenmeyer azlactone synthesis can be synthesized by reaction of aromatic aldehydes with an aromatic carboxylic acid may be brought (e.g. hippuric acid ) in the presence of acetic anhydride to the reaction.

The Erlenmeyer synthesis is still known by other names: Erlenmeyer Plöchl reaction Erlenmeyer Plöchl synthesis and Erlenmeyer Plöchl azlactone synthesis.

Reaction mechanism

The oxygen atom of the hydroxy group of the carboxylic acid 1 accesses the acetic anhydride initially to nucleophilic. Acetic acid is split off it. By a keto -enol tautomerism, a further attack of the compound 3 to the aromatic aldehyde takes place, so that the compound 4 is formed. Under elimination of water and another tautomerism cyclization takes place. Thereafter, an acetic acid molecule is cleaved again to give the desired azlactone 8.

Representation of α -keto acids

From azlactones then can be obtained by saponification of α -keto acids produced:

Representation of α -amino acids

Is performed prior to the hydrolysis, hydrogenation of the C = C double bond, α -amino acids occur:

Variants

If one uses instead of hippuric acid hydantoin or rhodanine, you get the amino acids in higher yield.

A variant of the Erlenmeyer synthesis is the Erlenmeyer Plöchl synthesis, which was named after the chemists Emil Erlenmeyer and J. Plöchl.

Describes the synthesis of chemical reactions in which glycine can be represented in a number of amino acids over oxazolinone and azlactone.

Hippuric acid is in the presence of acetic anhydride to a self-condensation of 2-phenyl - oxazol -5- one This intermediate has two acidic protons and react with benzaldehyde, acetic anhydride and sodium acetate to azlactone. This in turn can respond to phenylalanine by reduction.

In one study, the Erlenmeyer amino acid synthesis was used as the core synthesis of Lm -tyrosine

Of benzyl 3- hydroxybenzaldehyde reacts with 1 via the N- Acetylamids glycine 2, and acetic anhydride to Natriumacatat azlactone ( not shown in the pathway ), which undergoes ring opening with sodium acetate in methanol to the dehydroamino acid 3. Subsequent hydrogenation yields the (RS)- N-acetyl- m- tyrosine methyl ester 4 (the benzyl ether group is also cleaved ), a racemate. A specific enzyme capable of cleaving only the methyl ester of (S)- enantiomer of 5, which is soluble in dichloromethane. What remains is the water-soluble (R) -4. The final step is the removal of the acetyl group of hydrochloric acid 5 (S )-m -tyrosine 6 supplies.