Hydantoins intermediate

When 5-bromo-6-methyluracils possessing a phenyl group at the N-l position are treated with alkylamines and hydrazine, ring contraction occurs to hydantoins and 3-pyrazolones, respectively. The latter conversion into the pyrazolone is a double-ring transformation via a hydantoin intermediate. The N-l-phenyl group is essential for of the ring contraction to... 

Glycblor . [Lonza] l,3-Dichloro-S,S dimethyl hydantoin intermediate fot custom chemical synthesis, laundry bleach formulations, automatic dishwashing conqxls. 

An unexpected feature of the chemistry of the above ureido ester analogues was the apparent ease with which they underwent at least partial racemization at the a-carbon during alkaline hydrolysis to ureido acids. Support for the conclusion that racemization was taking place came from a combination of direct polarometric measurements on the ureido diacids (low rotation in comparison with MTX and folic acid) and indirect evidence that hydrolysis was proceeding via a hydantoin intermediate. Thus, when the ester (VI.9) was heated in MeOH or CHCI3 in the presence of the strong organic base l,5-diazabicyclo[3.4.0]non-5-ene, a product formed in 61% yield which was tentatively identified as (VI.15). Alkaline hydrolysis of (VI.15) yielded (VI.8). 

Uses, cx-Aminonitriles may be hydrolyzed to aminoacids, such as is done in producing ethylenediaminetetracetate (EDTA) or nittilotriacetate (NTA). In these cases, formaldehyde is utilized in place of a ketone in the synthesis. The principal use of the ketone-based aminonitriles described above is in the production of azobisnittile radical initiators (see below). AN-64 is also used as an intermediate in the synthesis of the herbicide Bladex. Aminonitriles are also excellent intermediates for the synthesis of substituted hydantoins by reaction with carbon dioxide however, this is not currently commercially practiced. 

Fig. 1. 5-Substituted hydantoins as synthetic intermediates. Equation 1 (45) equation 2 (46).

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. 

In summary, the Bucherer-Bergs reaction converts aldehydes or ketones to the corresponding hydantoins. It is often carried out by treating the carbonyl compounds with potassium cyanide and ammonium carbonate in 50% aqueous ethanol. The resulting hydantoins, often of pharmacological importance, may also serve as the intermediates for amino acid synthesis. 

A variant of the Strecker synthesis is the Bucherer-Bergs reaction it gives better yields, and proceeds via formation of an intermediate hydantoin 5 ... 

In many cases, the racemization of a substrate required for DKR is difficult As an example, the production of optically pure cc-amino acids, which are used as intermediates for pharmaceuticals, cosmetics, and as chiral synfhons in organic chemistry [31], may be discussed. One of the important methods of the synthesis of amino acids is the hydrolysis of the appropriate hydantoins. Racemic 5-substituted hydantoins 15 are easily available from aldehydes using a commonly known synthetic procedure (Scheme 5.10) [32]. In the next step, they are enantioselectively hydrolyzed by d- or L-specific hydantoinase and the resulting N-carbamoyl amino acids 16 are hydrolyzed to optically pure a-amino acid 17 by other enzymes, namely, L- or D-specific carbamoylase. This process was introduced in the 1970s for the production of L-amino acids 17 [33]. For many substrates, the racemization process is too slow and in order to increase its rate enzymes called racemases are used. In processes the three enzymes, racemase, hydantoinase, and carbamoylase, can be used simultaneously this enables the production of a-amino acids without isolation of intermediates and increases the yield and productivity. Unfortunately, the commercial application of this process is limited because it is based on L-selective hydantoin-hydrolyzing enzymes [34, 35]. For production of D-amino acid the enzymes of opposite stereoselectivity are required. A recent study indicates that the inversion of enantioselectivity of hydantoinase, the key enzyme in the... 

The soluble polymer support was dissolved in dichloromethane and treated with 3 equivalents of chloroacetyl chloride for 10 min under microwave irradiation. The subsequent nucleophilic substitution utilizing 4 equivalents of various primary amines was carried out in N,N-dimethylformamide as solvent. The resulting PEG-bound amines were reacted with 3 equivalents of aryl or alkyl isothiocyanates in dichloromethane to furnish the polymer-bound urea derivatives after 5 min of micro-wave irradiation (Scheme 7.75). After each step, the intermediates were purified by simple precipitation with diethyl ether and filtration, so as to remove by-products and unreacted substrates. Finally, traceless release of the desired compounds by cyclative cleavage was achieved under mild basic conditions within 5 min of micro-wave irradiation. The 1,3-disubstituted hydantoins were obtained in varying yields but high purity. 

Cyclative cleavage strategies release the final compound into solution following intramolecular attack of a nucleophile or electrophile upon the linkage site. Synthesis byproducts and intermediates do not incorporate the necessary nucleophile or electrophile therefore only the desired products are released into solution to yield high purity materials. Seminal examples of this approach are the library syntheses of benzodiazepines and hydantoins (Scheme 3). 

The hydantoin route for synthesis of the 2-oxoacid° has been performed with a variety of starting aldehydes and appears to work more reliably than the method described earlier. In spite of the restricted solubility of the intermediate oxoacid substrate for the biocatalytic step, the reaction proceeds to a good final overall yield with more substrate dissolving to replace that consumed in the reaction. The combined procedure appears to be quite versatile. 

A conceptually similar approach applied in an industrial process is described by the Bristol—Myers—Squibb group, who required l-6-OH norleucine as an intermediate in the synthesis of their drug Omapatrilat. T o avoid a lengthy chemical synthesis of the oxoacid, it was more convenient to start with the racemic amino acid, readily prepared by hydrolysis of the corresponding hydantoin (Equation (2)), and remove the D-isomer by oxidation using d-AAO. 

The scope of the reaction depends on the availability of the starting aldehyde (or ketone). A drawback is the toxicity of the hydrogen cyanide used as reactant. A variant of the Strecker synthesis is the Bucherer-Bergs reaction it gives better yields, and proceeds via formation of an intermediate hydantoin 5 ... 

A somewhat different scheme is used for the preparation of an all-aliphatic thio-hydantoin. Thus, reaction of racemic leucine (91-1) with allylisothiocyanate (91-2) leads to the thiourea (91-3). Attack of the anion from treatment of that intermediate with a strong base leads to ring closure and the formation of the imidazoline ring. There is thus obtained the anticonvulsant agent albutoin (91-4) [97]. 

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. 

The base-catalysed reaction sequence (formulated in Expt 8.17) is thought to proceed via an intermediate heterocyclic pinacol which on acidification yields the required hydantoin as a result of a pinacolic rearrangement. The procedure is applicable in general to diaryl-1,2-diketones. 

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