2- Naphthol Bucherer reaction with

Bucherer reaction Bucherer discovered that the interconversion of 2-naphthol and 2-naphthylamine through the action of alkali and ammonia could be facilitated if the reaction was carried out in the presence of (HSO3]" at about 150 C. This reaction is exceptional for the ease with which an aromatic C —OH bond is broken. It is not of general application, it is probable that the reaction depends upon the addition of [HSO3]" to the normally unstable keto-form of 2-naphthol, and subsequent displacement of —OH by —NH2. 

Nitration. Naphthalene is easily nitrated with mixed acids, eg, nitric and sulfuric, at moderate temperatures to give mostly 1-nitronaphthalene and small quantities, 3—5%, of 2-nitronaphthalene. 2-Nitronaphthalene [581-89-5] is not made in substantial amounts by direct nitration and must be produced by indirect methods, eg, the Bucherer reaction starting with 2-naphthalenol (2-naphthol [135-19-3]). However, the 2-naphthylamine [91-59-8] made using this route is a carcinogen thus the Bucherer method is seldom used in the United States. 

The AMAPs (2-[ arylmethyl amino]-l,3-propanediols) are a class of planar polycyclic aromatic derivatives, which contain polar side-chains. They are known to be DNA intercalators and possess broad spectrum antitumour activity. An approach to C-radiolabelled AMAP derivative 40 used the Bucherer reaction as an initial starting reaction. 2-Naphthol was reacted with 4-bromophenylhydrazine 38 in the presence of sodium metabisulfite and HCl to afford 39. Subsequent derivatisation of 39 afforded 40. 

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... 

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 ... 

P-Nitronaphthalene is not formed by direct nitration. For the preparation of p-naphthylamine, the Bucherer reaction may be applied to p-naphthol, i.e., by heating with ammoniacal ammonium sulphite solution at 150° (under pressure). The reaction involves the addition of the bisulphite to the keto form of p-naphthol ... 

P-Bromonaphthalene. The preparation from p-naphthylamine, which has carcinogenic properties, is avoided by the use of 2-naphthylamine-1-sulphonic acid ( 2-amino-1-naphthalenesulphonic acid ) the latter is obtained commercially by cautious treatment of p-naphthol with sulphuric acid—the SOjH group first enters the 1-position—followed by the Bucherer reaction. Diazotisation and reaction with cuprous bromide yields 2-bromonaphthalene-l-sulphonic acid heating with sulphuric acid eliminates the sulphonic acid group to give 2-bromonaphthalene. 

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. 

Naphthylamine is no longer manufactured and its laboratory preparation should never be attempted because of its potent carcinogenic properties. For many preparative purposes (e.g. see 2-bromonaphthalene, cognate preparation in Expt 6.72, and 2-naphthoic acid, Expt 6.154), 2-naphthylamine-l-sulphonic acid may be used. This is obtained commercially by cautious treatment of 2-naphthol with sulphuric acid - the sulphonic acid group entering the 1-position - followed by a Bucherer reaction. 

Amination. Very few reactions of general scope exist for the direct conversion of alcohols to amines. Among one of the oldest is the Bucherer reaction which is used to convert naphthols (40) and phenols (41) to their amine derivative by reaction with aqueous sodium bisulphite and ammonia (Reaction XXV). 

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... 

Substituents directly attached to fused benzene rings or aryl groups mostly show the reactions of those on benzenoid rings. Thus, a substituent on the benzenoid ring in quinoline or isoquinoline should be compared with that on a naphthalene rather than with a benzene nucleus for example, such hydroxy derivatives undergo the Bucherer reaction, ArOH + (NH4)2S03 ArNH2, typical for naphthols (see also Section 3.2.3.2.2). 

The Bucherer reaction is also applicable with certain compounds in the benzene and anthracene series, but it is of practical significance only with naphthalene compounds. The reaction can be used with both a- and -naphthols or... 

The Bucherer method has completely replaced the older procedure of heating the naphthol with ammonia. This process gave only about a 70 per cent yield at pressures of 50 to 60 atmospheres. The Bucherer reaction was discussed in more detail on page 182. 

The conversion of 2-naphthol-l-sulfonic acid into the corresponding niiphthyl-aminesulfonic acid is another example of the Bucherer reaction which wsulfonic acid (page 182). 

The naphthylamines may be prepared by reduction of the corresponding nitro compound, but they are readily accessible from naphthois by the Bucherer reaction The naphthol is heated, preferably under pressure in an autoclave, with ammonia and aqueous sodium hydrogen sulfite solution, when an addition-elimination sequence occurs. The detailed mechanism is not completely elucidated, but the Bucherer reaction is restricted to those phenols that show a tendency to tautomerize to the keto form, such as the naphthois and 1,3-dihydroxybenzene (resorcinol). Using 1-naphthol for illustration, the first step is addition of the hydrosulfite across the 3,4-double bond of either the enol or keto tautomer (Scheme 12.9). Nucleophilic attack by ammonia at the carbonyl group... 

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). 

Bucherer reaction. A procedure for preparation of (i-naphthylamineby heating (i-naphthol with a water solution of ammonium sulfite. A sulfite solution is prepared by saturating concentrated ammonia solution with sulfur dioxide and adding an equal volume of concentrated ammonia solution, (i-naphthol is added and the charge is heated in an autoclave provided with a stirrer or a shaking mechanism. (L. F. Fieser). This reaction is also involved in the preparation of several azo dye intermediates, e.g., Tobias acid. 

Aryl hydrazines can also be prepared according to the principles of the Bucherer reaction, namely by treating appropriate phenols with hydrazine hydrate and sulfur dioxide.1070-1073 Thus 2,3-naphthalenediol affords 57% of 2,3-naphthylenedihydrazine,1070 1071 and 2,7-naphthalenediol affords 82% of 7-hydrazino-2-naphthol.1072 However, no great importance attaches to these reactions. 

The amination of naphthalene using primary or secondary amines is one type of modification, and the treatment of naphthol with a complex of Lewis acid and ammonia is another modification. The latter was reported before the Bucherer reaction was published. 

Scheme 835. A possible path for the amiaolysis of P-naphthol (the Bucherer reaction or the Budierer-LePetit reaction). It is suggested that bisulfite adds to the aromatic ring, the phenolic hydroxyl tautomerizes, an addition reaction of ammonia to the carbonyl carbon occurs with loss of water, and, finally, the imine so generated tautomerizes, bisulfite is lost, and the aminonaphthalene is produced.

The Bucherer reaction is a useful, though limited, method of deamination . As an example, treatment of naphthylamines with aqueous sodium bisulfite at 160° followed by sodium hydroxide at 100° gives naphthols (equation 178) . The reaction is reversible... 

The Bucherer carbazole synthesis was first demonstrated when 7 was heated in the presence of phenylhydrazines 8, sodium hydroxide and sodium bisulfite after acidic work-up, the benzocarbazole product 9 was isolated (-70% yield). When 2-naphthol was used the reaction was significantly slower with the yield of benzocarbazole being only 46% after several days at 130 °C Bucherer and co-workers investigated this reaction extensively concluding, incorrectly, that intermediate products were probably carbazole-Al-sulfonic acids due to the ease with which they lost the sulfonic acid residues to yield benzocarbazoles. 

Naphthols as well as naphthylamines are converted to labile intermediate compounds by the action of bisulfite. These intermediates were considered to be sulfurous acid esters of naphthols (Formula I) by Bucherer, the discoverer of the reaction, but Woroshtzow formulated them as addition products of bisulfite with the keto forms of the naphthols (Formula II). These intermediates yield the corresponding naphthylamines with ammonia, and are hydrolyzed to the naphthols by caustic allrali. Thus, it is possible to convert naphthok into naphthylamines (pages 200 and 203), as well as naphthylamines into naphthols. ... 

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