Bucherer reaction

Gilbert, E. E. Sulfonation and Related Reactions Wiley New York, 1965, pi 66. 

The chloromethylation can be generally employed in aromatic chemistry benzene, naphthaline, anthracene, phenanthrene, biphenyls and many derivatives thereof are appropriate substrates. The benzylic chlorides thus obtained can be further transformed, for example to aromatic aldehydes. Ketones like benzophe-none are not reactive enough. In contrast phenols are so reactive that polymeric products are obtained.  

An important side reaction is the formation of diaryl methane derivatives ArCHaAr. Moreover poly substituted products may be obtained as minor products. Aromatic compounds have been treated with formaldehyde and hydrogen bromide or hydrogen iodide instead of hydrogen chloride. The formaldehyde may be replaced by another aldehyde the term Blanc reaction however stands for the chloromethylation only. 

An important reaction in the chemistry of naphthalenes is the Bucherer reaction,i.e. the conversion of naphthols 1 to naphthylamines 2 as well as the reverse reaction. The reaction is carried out in aqueous medium in the presence of catalytic amounts of a sulfite or bisulfite. Apart from very few exceptions it does not apply to benzene derivatives, which limits the scope of that reaction. 

Naphthol 1 is initially protonated at a carbon center of high electron density (C-2 or C-4). The cationic species 3 thus formed is stabilized by resonance it can add a bisulfite anion at C-3. The addition product can tautomerize to give the more stable tetralone sulfonate 4 the tetralone carbonyl group is then attacked by a nucleophilic amine (e.g. ammonia). Subsequent dehydration leads to the cation 

5 which again is stabilized by resonance. Loss of a proton leads to the enatnine 6, which upon loss of the bisulfite leads to the aromatic naphthylamine 2  

Transformation of P-naphthols to P-naphthylamines using ammonium sulfite. 

Although the classic Bucherer reaction requires high temperature, it may be carried out at room temperature with the aid of microwave (150 watts)  

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 37, Springer-Verlag Berlin Heidelberg 2009 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 42, Springer International Publishing Switzerland 2014 

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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. 

The reversibility of the Bucherer reaction is utilised in the preparation of 2-p-tolylamino-5-hydroxynaphthalene-T-3ulphonic acid (II) from 2-amino-... 

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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. 

By the Bucherer reaction (with sulfite) of the appropriate arninonaphthalenesulfonic acid. 

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 mechanism of the Bucherer reaction amounts to a kind of overall addition-elimination ... 

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. 

Self accelerating decomposition (Q = 0.43 kJ/g) occurs at 130°C in closed systems, such as are used for the Bucherer reaction. 

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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... 

In the above reaction mechanisms it is noteworthy that the sulphonic acid group introduced has been shown to enter at the 3-position and not the 4-position as previously postulated. A consequence of this situation is that an attempted Bucherer reaction on a naphthol (or a naphthylamine) carrying a sulphonic acid group located meta to the hydroxy (or amino) group would require a second sulphonic acid group to be introduced at this position. Since it is impossible to locate two sulphonic acid groups on the same carbon atom, these compounds cannot undergo the transformation. 

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. 

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