5- -hydantoin, synthesis

The above reaction is an example of Bucherer s hydantoin synthesis. The following mecJiavism has been proposed ... 

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

In a modification of the original method. Read (60) replaced a-amino acids with a-amino nitriles. This reaction is sometimes known as Strecker hydantoin synthesis, the term referring to the reaction employed for the synthesis of the a-amino nitrile from an aldehyde or ketone. The cycli2ation intermediate (18) has been isolated in some cases (61), and is involved in a pH-controUed equiUbrium with the corresponding ureide. 

Imidazo[2,l-c][l,2,4]dithiazole-3-thione, 5,6-dihydro-synthesis, 6, 1016 Imidazo[ 1,2-c]hydantoin synthesis, 6, 991... 

The first improvement of the Bucherer-Bergs reaction was the Bucherer-Lieb variation using the diluted alcoholic solution as described at the end of section 7.2.2. The Bucherer-Lieb variation is possibly the most popular process for synthesizing hydantoins. Another notable variation is the Henze modification using fusing acetamide as the solvent in place of water, benzene or 50% alcohol. Recently, ultrasound-promoted hydantoin synthesis has been reported to accelerate the reaction. 

Bucherer hydantoin synthesis, 843, 844 Bucherer reaction, 561, 568, 569 Bumping of liquids, 3, 4... 

URECH HYDANTOIN SYNTHESIS. Formation of hydantoins from o -amino acids by treatment with potassium cyanate in a aqueous solution and heating of the salt of the intermediate hydantoic acid with 25% hydrochloric acid. 

Fig. 3. Further examples of hydantoin synthesis by cyclative cleavage.

Monosubshtuted hydantoins are a-amino acids cyclically protected at both the carboxyl- and the a-amino group. They can be easily prepared from an aldehyde and isocyanate or by the Bucherer-Bergs synthesis and similar methods. Indeed, the hydantoin synthesis is also a prachcal method for the preparahon of the racemic amino acid. Enzymes belonging to the dihydro-pyrimidinase family hydrolyze hydantoins to the carbamoyl amino acid. The latter can be hydrolyzed in turn to the amino acid by a second enzyme, a carbamoylase. Both enzymes can discriminate between enantiomers and, if their action is cooperative, either the L- or the D-amino acid can be obtained (Scheme 13.10) [36]. What makes the system of special interest is that the proton in the 5-position of the hydantoin ring (it will become the a-hydrogen in the a-amino acid) is considerably more acidic than conventional protons in amino acid esters or amides and much more acidic than the amino acid itself. Thus, the hydantoin can be often racemized in situ at slightly basic pH where the enzymes are stiU stable and active. If these condihons are met. 

The Bucherer-Bergs hydantoin synthesis has been employed to build spiro compounds 221 as 5-HTlA modulators [81]. The compounds were prepared from... 

Treatment of a-azido esters 1290 with triphenylphosphine gives -phosphazides 1291, which subsequently react with isothiocyanates to afford thiohydantoins 1292 after aqueous work-up. The cyclization conditions can also be adapted to hydantoin synthesis when isocyanates are used (Scheme 328) <2004TL1655>. 

T. Ohashi, S. Takahashi, T. Nagamichi, K, Yoneda, and H. Yamada, A new method for 5-(4-hydroxyphenyl) hydantoin synthesis, Agric. Biol. Chem., 45 831 (1981). 

A re-evaluation of soHd-phase hydantoin synthesis, including aspects of improved retention of chirality, has recently been published [27]. A method with an emphasis on chemical robustness and practical efficiency has been developed, in which the intermediates are anchored on Rink resin through a stable amide bond [28]. 

Phenylglycine doesn t occur in proteins but is available as either enantiomer. When Schering-Plough made the racemic drug 251 as an NK1 antagonist, the task was easy. Because a trusty hydantoin synthesis already existed, they mixed the ketone 253 with potassium cyanide and ammonium carbonate to get 252 and reduced out the spare amide carbonyl with LiAlH4. 

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis. Bucherer reaction. . ... 

---