Bucherer substitution

V-Alkyl and A/-aryl substituted naphthyl amines are also important, eg, letter acid derivatives, but are usually manufactured by the Bucherer reaction. 

In a German patent issued in 1929, Bergs described a synthesis of some 5-substituted hydantoins by treatment of aldehydes or ketones (1) with potassium cyanide, ammonium carbonate, and carbon dioxide under several atmospheres of pressure at 80°C. In 1934, Bucherer et al. isolated a hydantoin derivative as a by-product in their preparation of cyanohydrin from cyclohexanone. They subsequently discovered that hydantoins could also be formed from the reaction of cyanohydrins (e.g. 3) and ammonium carbonate at room temperature or 60-70°C either in water or in benzene. The use of carbon dioxide under pressure was not necessary for the reaction to take place. Bucherer and Lieb later found that the reaction proceeded in 50% aqueous ethanol in excellent yields for ketones and good yields for aldehydes. ... 

As mentioned above, the scope of the Bucherer reaction is limited. It works with anthracenes and phenanthrenes, but only very few examples with substituted benzenes are known. Naphthylamines can be converted into the corresponding naphthols, and these can then be further converted into primary, secondary or tertiary naphthylamines (transamination). Naphthylamines are of importance for... 

Based on observations by Bamberger, Bucherer, and Wolff at the turn of the century, Matrka et al. (1967) described experiments which show that alkaline solutions (pH 8.5-9.2) of substituted benzenediazonium chlorides form nitrite ions and triazenes. The latter is obviously the reaction product of the amine formed in a retro-diazotization with the diazonium ion that is still present. The yield of nitrite formed was between 0.5% (benzenediazonium ion) and 50.2% (2-nitrobenzenediazonium ion). 

Racemic hydantoins result from the reaction of carbonyl compounds with potassium cyanide and ammonium carbonate or the reaction of the corresponding cyanohydrins with ammonium carbonate (Bucherer-Bergs reaction). Hydantoins racemize readily under basic conditions or in the presence of hydantoin racemase, thus allowing DKR (Figure 6.43). Hydantoinases (EC 3.5.2.2), either isolated enzymes or whole microorganisms, catalyze the hydrolysis of five-substituted... 

The reaction of naphthols with ammonia and sodium bisulfite is called the Bucherer reaction. Primary amines can be used instead of ammonia, in which case N-substituted naphthylamines are obtained. In addition, primary naphthylamines can be converted to secondary, by a transamination reaction ... 

The Bucherer reaction can also be used in the preparation of substituted naphthylamines. Carrying out the reaction on a naphthol but employing an alkylamine in place of ammonia results in the production of the corresponding N-alkylnaphthylamine. Alternatively, a... 

Aminobenzo[6]thiophene-2-carhoxylic acids are conveniently obtained by reduction of the corresponding nitro compound.152,185,333, 334,33c, 338,497 Djazotization of these, followed by the usual replacement reactions of the diazonium group, provides many substituted benzo[6]thiophene-2-carboxylic acids, decarboxylation of which leads to some otherwise rather inaccessible benzo[6]thiophenes. 5-Hydroxy-benzo[6]thiophene-2-carboxylic acid is most conveniently prepared from the corresponding amino compound by means of the Bucherer reaction,338,497 in which the dicarboxylic acid (303) is formed as a by-product.152... 

The direct replacement of the hydroxyl group in simple phenols by an amino or substituted amino group requires drastic conditions and the method is not suitable for laboratory preparations. With the polyhydric phenols, and more particularly with the naphthols, such replacements occur more readily. Thus 2-naphthol is converted into 2-naphthylamine by heating with ammoniacal ammonium sulphite solution at 150°C in an autoclave. The reaction (the Bucherer reaction) depends upon the addition of the hydrogen sulphite ion to the keto form of the naphthol and the subsequent reaction with ammonia. 

An important amination reaction involves hydroxy-substituted naphthalenes (Fig. 13.53). In a process known as the Bucherer reaction, naphthols are heated under pressure with a mixture of ammonia and sodium bisulfite. As... 

The alteration of nucleophilic reactivity by the intervention of covalent hydration and analogous nucleophilic additions needs to be borne in mind for many polyazanaphthalenes. Covalent hydration has been observed in several bicyclic azines besides pteridine and quinazoline (Section IV, B) and is related to nucleophilic substitution in activation and in proceeding through the same first stage as 8 Ar2 reactions. The Bucherer interconversion of naphthols and naphthylamines involves exchange of oxygen and nitrogen substituents in a covalent adduct produced by bisulfite ion. ... 

This equilibrium reaction in the presence of sulfites is used for the preparation of naphthols and naphthylamines (Bucherer reaction) (cf. method 438). A review of the literature to 1942 has been made. The substituted naphthalenes are heated with aqueous sodium bisulfite at 90-150°. Nearly quantitative yields of a- and /3-naphthols are obtained from the corresponding naphthylamines. Many substituted naphthols have been prepared by this procedure. 

The (x-substituted naphthalenes, like substituted benzenes, are ihpst commonly prepared by a sequence of reactions that ultimately goes back to a nitro compound (Sec. 30.8). Preparation of / -substituted naphthalenes, on the other hand, cannot start with the nitro compound, since nitration does not take place in the j3-position. The route to /3-naphthylamine, and through it to the versatile dia-zonium salts, lies through /9-naphthol. /9-Naphthol is made from the /3-sulfonic acid it is converted into /8-naphthylamine when heated under pressure with ammonia and ammonium sulfite (the Bucherer reaction, not useful in the benzene series except in rare cases). 

A one-pot procedure was developed for the preparation of aromatic amines from phenols via a one-pot Smiles rearrangement by N.P. Peet et al.° This new approach can be considered as an alternative of the Bucherer reaction which only works well for naphthalene derivatives and gives very poor yields for substituted benzene derivatives. In the current procedure, the phenol was reacted with 2-bromo-2-methylpropionamide to give 2-aryloxy-2-methylpropionamide which upon treatment with base underwent the Smiles rearrangement. The hydrolysis of the resulting A/-aryl-2-hydroxypropionamide afforded the aromatic amine. 

Bucherer, H. T., Libe, V. A. Syntheses of hydantoins. II. Formation of substituted hydantoins from aldehydes and ketones. J. Prakt. Chem. 

Cyanoethylation of pyridazines and related N-alkylations are described. The Michael-type addition of maleic hydrazide or related pyridazinones with a, -unsaturated carbonyl compounds give N-substitution products (120). These can be converted via hydantoins or by Bucherer... 

The enzyme, Af-carbamoyl o-amino acid amidohydrolase can be incorporated with hydantoinase to produce o-amino acids in one step from the corresponding racemic hydantoins. Because many of the five-substituted hydantoins undergo spontaneous racemization under the enzymatic reaction conditions (pH > 8), complete conversion from racemic hydantoin to the o-amino acid can be achieved. The starting hydantoins are prepared by the Bucherer-Bergs reaction (Scheme 9.34), the simple condensation of potassium cyanide and ammonium carbonate with the... 

If cyanohydrins are treated with ammonium carbonate instead of ammonia, 5-substituted hydantoins are obtained, usually in very good yield (the Bucherer-Henze synthesis) 979... 

Conversion of Naphthols to Naphthylamines. Sulfurous Add Salts as Catalysts (Bucherer Reaction). The most general method for the replacement of —OH by —NHj groups in naphthols is the use of ammoniacal solutions containing salts of sulfurous acid. The alkali metal bisulfites are ordinarily employed in the preparation of primary amines but other compounds, such as the sulfite of methylamine (CH3-NHj)jSOj, can be used in making substituted amines. As can be seen from the reaction... 

Sodium bisulfite may be substituted for the ammonium salt without decreasing the yields of /3-naphthylamine obtained by the Bucherer reaction. In the course of the reaction, this is converted to the sodium ammonium salt in the presence of an excess of ammonia. About 0.6 mole of sodium ammonium sulfite per mole of /3-naphthol is necessary. 

Superti-Furga, A. Eich, G. Bucher, H.U. Wisser, J. Giedion, A. Gitzel-mann, R. Steinmann, B. A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia. Eur. J. Pediatr., 154, 215-219 (1995)... 

Beller s group described a pioneering palladium-catalyzed one-pot synthesis of 5-substituted hydantoins 27, 3,5-substi-tuted hydantoins 28, and 1,3,5-substituted hydantoins 30 based on the carbonylation of aldehydes in the presence of urea derivatives as an interesting alternative to Bucherer-Bergs reactions (Scheme 10.6) [29]. 

More recently, based on a Bucherer-Bergs protocol, Conway and coworkers have developed a one-pot gallium(III) triflate-catalyzed synthesis of 5-substituted and 5,5-disub-stituted hydantoins 31 from the corresponding aldehydes and ketones in CH Clj (Scheme 10.7) [30], This one-pot synthesis of hydantoins avoids the difficulty associated with the isolation and purification of the a-aminonitrile intermediate in these processes. 

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