Hydantoin reaction mechanism

Figure 12.1 Reaction mechanism of the 5-monosubstituted hydantoins keto-enol tautomerism under alkaline conditions.

Proposal for a Reaction Mechanism of Hydantoin Racemase Enzymes... 

Similar reactions transform DL-5-monosubstituted hydantoins to L-amino acids. Yo-kozeki et al. [11] analyzed the reaction mechanism of L-tryptophan production from dl-5-(3 -indolylmethyl)hydantoin by Flavobacterium sp. and found that nonstereospecific hydrolysis of hydantoin derivative and the L-sj ific hydrolysis of racemic A-carbamoyl amino acid were involved in this transformation. Yamashiro et al. [12] found the L-specific hydrolysis of a hydantoin derivative in L-valine production firom DL-5-isopropylhydantoin by Bacillus sp. and that ATP was absolutely required for this amidohydrolytic reaction. 

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

Synthesis From Aldehydes and Ketones. Treatment of aldehydes and ketones with potassium cyanide and ammonium carbonate gives hydantoins in a one-pot procedure (Bucherer-Bergs reaction) that proceeds through a complex mechanism. Some derivatives, like oximes, semicarbazones. Iliiosetricarbazones. and others, are also suitable starting materials. 

Topaquinone (TPQ), the oxidized form of 2,4,5-trihydroxyphenylalanine (TOPA), is the cofactor of copper-containing amine oxidases. The following model compounds have been prepared in order to understand the catalytic function of TPQ the jV-pivaloyl derivative of 6-hydroxydopamine in aqueous acetonitrile [38] topaquinone hydantoin and a series of 2-hydroxy-5-alkyl-l,4-benzoquinones in anhydrous acetonitrile (o- as well as />-quinones) [39] 2-hydroxy-5-methy 1-1,4-benzoquinone in aqueous system [40] and 2,5-dihydroxy-1,4-benzoquinone [41]. Reaction of model compounds with 3-pyrrolines revealed why copper-quinopro-tein amine oxidases cannot oxidize a secondary N [42], The studies clearly showed that certain model compounds do not require the presence of Cu for benzylamine oxidation whereas TPQ does [38,40] the aminotransferase mechanism proceeds via the -quinone form [39] the 470 nm band can be ascribed to a 71-71 transition of TPQ in />-quinonic form with the C-4 hydroxyl ionized but hydrogen bonded to some residue [40] hydrazines attack at the C-5 carbonyl, forming an adduct in the azo form [41], Electrochemical characterization has been carried out for free TPQ [43],... 

Fig. 7.12. Mechanism for the formation of hydantoin from 3-(methylthio)propional-dehyde, ammonium hydrogen carbonate and sodium cyanide, the initial reaction of the Strecker/Bucherer synthesis of methionine according to Figure 7.11.

More direct evidence for mechanism (20a) may be adduced from the observation that hydantoin 3-acetic acid (XIV) can be isolated from the reaction between glycine NCA and lithium chloride in AT.AT-dimethyl-formamide solution (eqn. (22)) [37, 39]. 

The presence of a substituent in the 3-position of the NCA precludes equilibrium (6) and hence prevents the occurrence of reaction (18). It follows that, on the basis of the mechanisms described above, such NCA s should not polymerize unless a protic base (for example a primary or secondary amine) or other source of protons (for example, 3-methyl hydantoin) is present. If it could be established that polymerization does proceed with an aprotic base in aprotic media then some other mechanism of polymerization must be operative. This matter has been of central importance in discussions of various mechanisms of polymerization which have been advanced (Section 3). Experimentelly, it is not easy to obtain definitive evidence because of the high sensitivity of NCA s to protonic impurities (such as water and alcohols) in the presence of bases. It has been shown [18, 19, 38a] that proline NCA (X) and sarcosine NCA (I Ri = R2 = H, R3 = CH3) do not polymerize in the presence of tertiary bases under strictly aprotic conditions. With alkoxides, realization of such conditions is difficult, but it would appear that, at least with proline NCA, such strong bases can bring about ionization of the methine hydrogen and hence initiate polymerization as shown in (26). Evidence for this mechanism is provided by the observation that while sodium methoxide enriched... 

The Bucherer-Bergs synthesis is of general application to carbonyl compounds, employing potassium cyanide and ammonium carbonate.1,4 Carbonyl derivatives such as semicarbazones, thiosemicarbazones, oximes, azines, phenylhydrazones, imidazolidines, and azomethines also are readily converted directly to the corresponding hydantoins 44 The extent to which the reaction occurs appears unrelated to the hydrolytic stability of the starting material. The proposed mechanism is given in Scheme 1. 

Next, BrCN reacts with pyridine to yield glutaconic aldehyde. This aldehyde is condensed with an aromatic amine such as p-phenylenediamine [9,10], benzidine [11,12], barbituric acid, 2,4-quinolinediol, 2,5-piperazinedione and hydantoin [9-13] to form a red polymethine dye. The molar absorptivities at An x = 530 nm are 6.0 x 10 and 3.1 x 10 for benzidine and p-phenylenediamine, respectively. The probable mechanism of the reaction with p-phenylenediamine is explained by Botto et al. [10] ... 

It has been shown (Pinazzi et al, 1%3) that reaction can be accelerated by a variety of catalysts such as azodiisobutyronitrile and chlorobromodimethyl-hydantoin as well as by peroxides. This is clear evidence that the reaction involves a free radical mechanism rather than a specific mechanism involving the peroxide group. The degree of addition (expressed as the number of maleic anhydride units added on per 100 isoprene units) is usually less than 25. The tendency to gel is a problem but this is reduced by the use of amines such as diethylamine. 

In the presence of tertiary amines, bismaleimides will undergo polyaddition reaction with hydantoin, bishydantoins, " or thio-hydantoins to give moldings and laminates with good heat resistance, mechanical and electrical properties. It is assumed that resin prepared from A,A -[4,4-diphenyl(methane)] bismaleimide and hydantoin has the following structural unit. 

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