And the Bucherer reaction

Bisulfite Addition Products and the Bucherer Reaction. The addition of sodium bisulfite to aldehydes and some ketones superficially appears to involve the addition of the elements Na and HS03 to the carbonyl group. Kinetic studies, however, indicate that the reaction is complicated and probably involves sulfite rather than bisulfite ion.10 One possible mechanism is the following ... 

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. 

Hydroxyisoquinolines. Hydroxy groups in the 5-, 6-, 7-, and 8-position show phenoHc reactions for example, the Bucherer reaction leads to the corresponding anainoisoquinolines. Other typical reactions include the Mannich condensation, azo-coupling reactions, and nitrosation. Both 0-methyl and /V-methyl derivatives are obtained from the methylation of 1-hydroxyisoquinoline, indicating that both tautomeric forms are present. Distillation of various hydroxy compounds, eg, 1- and 4-hydroxyisoquinoline, with zinc dust removes the oxygen. Treatment of 1-isoquinolinol with phosphoms tribromide yields 1-bromoisoquinoline [1532-71 -4] (178). 

Amination of phenoHc derivatives is limited to specially developed catalytic processes for aniline and y -toluidine (3). More general conditions apply to amination of naphthols by the Bucherer reaction. Important intermediates made by a Bucherer reaction include Tobias acid and gamma acid. 

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

When naphthyl amines e.g. 23) are used in the Bucherer carbazole synthesis, they are converted by the catalytic action of aqueous bisulfite into tetralonesulfonic acid derivative 13 by the Bucherer reaction. Addition of NaHSOs gives an enamine, which tautomerises to the imine 24 24 is hydrolysed to keto form 13 and subsequent Bucherer carbazole synthesis follows to afford the benzocarbazole product 20. ... 

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. 

Every step of the Bucherer reaction is reversible, and the reverse sequence is also of synthetic value. The equilibrium can be shifted by varying the concentration of free ammonia. ... 

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... 

A slightly related reaction involves the amino group of naphthylamines can be replaced by a hydroxyl group by treatment with aqueous bisulfite. The scope is greatly limited the amino group (which may be NH2 or NHR) must be on a naphthalene ring, with very few exceptions. The reaction is reversible (see 13-6), and both the forward and reverse reactions are called the Bucherer reaction. 

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 reversibility of the Bucherer reaction is utilised in the preparation of 2-p-tolylamino-5-hydroxynaphthalene-7-sulphonic acid. 5-hydroxynaphthalene-7-sulphonic acid or J acid p-toluidine and sodium bisulphite solution ... 

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. 

In some cases where it is difficult to carry out the Bucherer reaction successfully, it is easier to prepare N-arylnaphthylamines by heating together a naphthylamine and an arylamine. In particular, this reaction is useful in the preparation (Scheme 4.24) of 1-phenylaminonaphthalene-8-sulphonic acid (4.34 N-Phenyl Peri acid) and its N-4-methylphenyl analogue (Tolyl Peri acid), both of which intermediates are valuable components for the production of navy blue dyes. 

Problem 19.29 Use the Bucherer reaction to prepare 2-(N-methyl)- and 2-(N-phenyl)naphthylamines. CHjNHj and C HjNH replace NH,. 

Based on this tautometism, certain addition and replacement reactions at the hydroxyl or keto groups can be effected easily as with certain reactions of resorcinol and 2-naphthalenol. Thus, phloroglucinol forms a trioxime with hydroxylamine (120) it forms mono-, di-, and ttiaddition compounds with sodium bisulfite (121) it undergoes the Bucherer reaction with ammonia at room temperature (122) to give at first phloramine... 

An exception to the generalization that C—O bonds to aromatic systems are difficult both to make and to break is provided by reversible conversion of benzenediols and 1- or 2-naphthalenols to the corresponding amines, usually at elevated temperatures with sodium hydrogen sulfite or an acidic catalyst. The sodium hydrogen sulfite-induced reaction is called the Bucherer reaction ... 

Aminobenzo[6]thiophene is prepared from 7-hydroxybenzo[6]-thiophene by means of the Bucherer reaction it may be converted into 7-nitrobenzo[6]thiophene via the diazonium salt.84 5,7-Diamino-3-phenylbenzo[6]thiophene and its 2-carboxylic acid are prepared by reduction of the corresponding dinitro compound.334 Partial reduction of o,7-dinitro-3-phenylbenzo[6]thiophene-2-carboxylic acid with ethanolic ammonium sulfide affords 7-amino-5-nitro-3-phenylbenzo-[6]thiophene-2-carboxylic acid, the amino group of which may be replaced by hydrogen or iodine via the diazonium salt.334 7-Amino-4-methoxybenzo[6]thiophene is mentioned in the patent literature.560... 

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. 

The Bucherer reaction is illustrated and its reversibility demonstrated in Expt 6.55, wherein the amino group of 2-amino-5-naphthol-7-sulphonic acid is replaced by the p-tolylamino group via the corresponding naphthol intermediate. 

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... 

Other important hydroxylation reactions are shown in Fig. 13.70. Here it can be seen that the Bucherer reaction is reversible, that the fusion reaction works for sulfonated benzene compounds, and that diazonium compounds undergo hydrolysis to produce phenols/naphthols. 

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 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... 

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