Biltz synthesis

Condensation of urea with carbonyl compounds A rapid and efficient MW-assisted synthesis of hydantoins and thiohydantoins was described by Muccioli et al. [117]. The most straightforward conditions for synthesis of phenytoin are the base-catalyzed condensation using benzil and urea, known as the Biltz synthesis (Eq. 33). MW activation of the Biltz synthesis of phenytoin improved both yield and reaction time. The first step consists in MW activation of the reaction of benzil with (thio)urea the second includes the conversion of the resulting 2-(thio)hydantoin to hydantoin using hydrogen peroxide. When reactions were performed at the same temperature under both reaction conditions, yields were by far better under the action of MW and emphasized the evident specific MW effects. These are perfectly expected when one considers the polar TS involved in the first step (nucleophilic addition of neutral NH2 group on carbonyl moiety). 

A rapid and efficient microwave-assisted synthesis of hydantoins and thiolydan-toins was reported by Muccioli et al. [74], The reaction is known as Biltz synthesis and is the base-catalysed condensation of benzil and urea. It was observed that microwave irradiation reduced the reaction time as well as increased the yield of the product as compared to the conventional method. The reason behind this is the involvement of polar transition state, i.e. nucleophilic addition of a neutral NH2 group to a carbonyl site (Scheme 11.21). The yield via the conventional method was 36 % when heated for 2 h whereas the yield via microwave irradiation was 80 % when heated only for 30 min. 

The ammines of cobalt(II) are much less stable than those of cobalt(III) thermal decomposition of [Co(NH3)6]Cl2 is characterized by reversible loss of ammonia, whereas that of [Co(NH3)6]Cl3 is not. In his classic dichotomy of complexes, Biltz regarded [Co (NH 3)3] Cl 2 as the prototype of the normal complex and [Co(NH3)6]Cl3 as that of the Werner or penetration complex. Hexaamminecobalt-(II) chloride has been prepared by the action of gaseous ammonia on anhydrous cobalt (II) chloride or by displacing water from cobalt(II) chloride 6-hydrate with gaseous ammonia. It may also be synthesized in nonaqueous solvents by passing dry ammonia through solutions of cobalt(II) chloride in ethanol, acetone, or methyl acetate. Syntheses in the presence of water include heating cobalt(II) chloride 6-hydrate in a sealed tube with aqueous ammonia and alcohol and the treatment of aqueous cobalt(II) chloride with aqueous ammonia followed by precipitation of the product with ethanol. The latter method is used in this synthesis. Inasmuch as the compound is readily oxidized by air, especially when wet, the synthesis should be performed in an inert atmosphere. 

Zirconium acetylacetonate was first prepared by Biltz and Clinch by the reaction of zirconyl nitrate and sodium acetylacetonate in water solution. The compound was crystallized as the 10-hydrate from a slightly acid solution and dehydrated by several crystallizations from alcohol. Von Hevesy and Logstrup later developed a method for the preparation of hafnium acetylacetonate that has been found applicable to the synthesis of the zirconium compound and this forms the basis of the present procedure. 

Biltz-Wittek synthesis of barbituric acids 13, 422 Bimolecular s. under Reduction BioSxygenation s. Oxidation, biochemical 4,4 -Bipyrazoles 12, 553 Birch reduction 12, 129 14, 79 Bisacetals... 

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