The Erlenmeyer–Plöchl azlactone and amino acid synthesis, named after

Friedrich Gustav Carl Emil Erlenmeyer Friedrich Gustav Carl Emil Erlenmeyer (July 14, 1864 – February 8, 1921), also known as Emil Erlenmeyer, Jr., was a German chemist and the discoverer of the Erlenmeyer-Plöchl azlactone and amino acid synthesis. He was the son of Richard August ...

who partly discovered the reaction, is a series of

chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...

s which transform an ''N''- acyl glycine to various other

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s via an

oxazolone Oxazolone is a chemical compound and functional group, with the molecular formula C3H3NO2. It was named in-line with the Hantzsch–Widman nomenclature and is part of a large family of oxazole based compounds. There are a total of 5 structural iso ...

(also known as an

azlactone Oxazolone is a chemical compound and functional group, with the molecular formula C3H3NO2. It was named in-line with the Hantzsch–Widman nomenclature and is part of a large family of oxazole based compounds. There are a total of 5 structural isom ...

Hippuric acid Hippuric acid ( Gr. ''hippos'', horse, ''ouron'', urine) is a carboxylic acid and organic compound. It is found in urine and is formed from the combination of benzoic acid and glycine. Levels of hippuric acid rise with the consumption of phenoli ...

, the

benzamide Benzamide is a organic compound with the chemical formula of C6H5C(O)NH2. It is the simplest amide derivative of benzoic acid Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benz ...

derivative of glycine, cyclizes in the presence of

acetic anhydride Acetic anhydride, or ethanoic anhydride, is the chemical compound with the formula (CH3CO)2O. Commonly abbreviated Ac2O, it is the simplest isolable anhydride of a carboxylic acid and is widely used as a reagent in organic synthesis. It is a col ...

, condensing to give 2-phenyl-

. This intermediate also has two acidic protons and reacts with

benzaldehyde Benzaldehyde (C6H5CHO) is an organic compound consisting of a benzene ring with a formyl substituent. It is the simplest aromatic aldehyde and one of the most industrially useful. It is a colorless liquid with a characteristic almond-like odor. ...

, acetic anhydride and sodium acetate to a so-called

. This compound on reduction gives access to

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

Variations

Variants of the azlactone synthesis in which analogues of azlactones are used are sometimes advantageous.

Hydantoin Hydantoin, or glycolylurea, is a heterocyclic organic compound with the formula CH2C(O)NHC(O)NH. It is a colorless solid that arises from the reaction of glycolic acid and urea. It is an oxidized derivative of imidazolidine. In a more general sen ...

(in Bergmann modification), thiohydantoin and

rhodanine Rhodanine is a 5-membered heterocyclic organic compound possessing a thiazolidine core. It was discovered in 1877 by Marceli Nencki who named it ''"Rhodaninsaure"'' in reference to its synthesis from ammonium rhodanide (known as ammonium thiocya ...

have each been employed as the enolate-forming component of the condensation. 2,5-Diketopiperazine can be used as a methylene component as well; its condensation products with aromatic aldehydes, on reduction and hydrolysis give the corresponding amino acids.

Scope

In one study the Erlenmeyer amino acid synthesis was used in the heart of an

L-m-tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard proteinogenic amino acid, amino acids that are used by cell (biology), cells to protein biosynthesis, synthesize proteins. It is a non-essential amino aci ...

synthesis The benzyl ether of

3-hydroxybenzaldehyde 3-Hydroxybenzaldehyde is an organic compound with the formula . It is a colorless solid although most samples appear tan. Two other isomers of hydroxybenzaldehyde exist. Preparation It has been prepared from 3-nitrobenzaldehyde in a sequence o ...

1 reacts with the N-acetyl

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...

of glycine 2,

and sodium acetate to the azlactone (not displayed) which is ring-opened with sodium acetate in methanol to dehydroamino acid 3.

Hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a Catalysis, catalyst such as nickel, palladium or platinum. The process is commonly employed to redox, reduce or S ...

gives the N-acyl-m-tyrosine methyl ester 4 (the benzyl ether group is also cleaved). This compound is racemic and kinetic resolution is brought about by an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

which is able to only cleave the methyl ester of the S-enantiomer (forming (''S'')-5 soluble in

dichloromethane Dichloromethane (DCM or methylene chloride, methylene bichloride) is an organochlorine compound with the formula . This colorless, volatile liquid with a chloroform-like, sweet odour is widely used as a solvent. Although it is not miscible with ...

) leaving water-soluble (''R'')-4 untouched. The final step is amide cleavage to (''S'')-L-''m''-tyrosine 6

References

{{DEFAULTSORT:Erlenmeyer-Plochl Azlactone And Amino Acid Synthesis Condensation reactions Heterocycle forming reactions Name reactions Chemical synthesis of amino acids

Variations

Scope

See also

References