Meisenheimer reactions

In the Meisenheimer reaction of quinoline 1-oxides chlorine atoms usually enter the 2-and 4-positions, but not exclusively. 2,4-Dibromoquinoline 1-oxide was 6-chlorinated (57MI1), and the 5- and 6-nitroquinoline 1-oxides were 3-chlorinated to some extent (44JOC302). This reaction with phosphoryl chloride-phosphorus pentachloride has also been used in the preparation of chlorinated phenanthrolines (88YZ1148). 

Chlorination. When 75 was treated with chlorine in the presence of aluminium chloride, initial chlorination took place at the 5-position, but the reaction was rather unselective 5,8-di-, 5,7,8-tri-, and 5,6,7,8-tetra-chloroisoquinolines were also formed (64JOC329). Perchlorination has been achieved by initial reaction of the isoquinoline-aluminium chloride complex with chlorine, as above, followed by treatment with phosphorus pentachloride at 270°C in an autoclave [66JCS(C)2328]. Treatment of 1,8-dimethylisoquinoline with NCS gave the 5-chloro derivative (91NKK-1193). Meisenheimer reaction of isoquinoline 2-oxides with phosphoryl chloride gave 1-chloroisoquinoline (84MI2). 

Nucleophilic halogenations tend to favor the pyridine moiety. The Meisenheimer reaction of thieno[3,2-6]pyridine N-oxide (125) gave only a 24% yield of a 1.4 1 mixture of the 5- and 7-chloro derivatives. Nucleophilic displacement of a 7-nitro group provided a more satisfactory route to the 7-chloro (73%) and 7-bromo (39%) derivatives (85JHC1249). 

Although the simple mono-(2-,4-,6-, and 7-) and some di-(6,7-, 2,4-) tri-(2,4,6-, 2,4,7-), and tetra-(2,4,6,7-) -chloro derivatives are known, they are often unstable and highly susceptible to nucleophilic attack, and little is known about some of the compounds (64JCS1666 84MI10). No electrophilic halogenations have yet been reported, but there have been a few instances of chlorine introduction by Meisenheimer reaction of pteridine N-oxides (78JOC680 82LA2135). 

An unsuccessful attempt to repeat this reaction was made by Bird however, he was able to show that dibenzothiophene 5-oxide did, in fact, react with either thionyl chloride or phosphorus oxychloride to yield 2-chlorodibenzothiophene in good yield. Since all methods of nitration of dibenzothiophene yield a mixture of 2-nitrodibenzothio-phene and dibenzothiophene 5-oxide, which have identical melting points, it was concluded that the earlier workers had in fact been working with the sulfoxide and not the nitro compound. The reaction was rationalized as being a deoxygenative halogenation of a heterocyclic 5-oxide akin to the Meisenheimer reaction of A-oxides, which already had precedents in the sulfoxide field. Unfortunately the 2-chlorodibenzothiophene prepared by this route is contaminated with 2,8-dichlorodibenzothiophene which cannot be removed by crystallization. The best method of preparation of this compound is therefore via a Sandmeyer reaction on 2-aminodibenzothiophene. ... 

Table 8 Meisenheimer Reaction Products of some l,x-Naphthyridine 1-Oxides (71JOC1720,72JOC3ioi>...

The Meisenheimer reaction of the l,X-naphthyridine 1-oxides has been examined in some detail.72 75 Table II lists the relative yields of the 2-, 3-, and 4-chloronaphthyridines formed. As the amount of 2-chloronaphthyridine decreases, the 3-chloro and 4-chloro isomers increase in the series 1,7-, 1,5-, 1,8-, and 1,6-naphthyridine. 

MEISENHEIMER REACTION PRODUCTS TROM l.X-NAl llTIlYRIDINF 1-OXIDES... 

Meisenheimer reactions of pyridazine TV-oxides give deoxygenated a-chloro derivatives. If the a-position is blocked, however, y-substitution... 

Heating with phosphoryl chloride converted 1 -hydroxy-3-phenyl-2( 1H )-pyrazinone (52) into the 2,5-dichloro derivative (53) via the 5-monochIoro species. It had been expected that chlorination would take place at C-6, but this occurred only to a minor extent. The observed chloride attack /3 to the oxygen function might be accounted for in terms of the sequence illustrated in Scheme 46 (86JHC149). Reaction mechanisms have been proposed to explain the observed a- and /3-chlorination when 2- and 3-substituted pyrazine Af-oxides are subjected to the Meisenheimer reaction. /3-Chlorination was rationalized in terms of electron withdrawal by the unoxidized nitrogen atom [84JCR(S)318] (Scheme 46). 

Formation of chlorides 445a,b and 446, in nearly quantitative yields, via the Meisenheimer reaction was accomplished by treatment of the corresponding 1,5-oxazocines 427a,d and 428d with MCPBA to give 443a,b and 444... 

Electrophilic substitution Nucleophilic addition and substitution Nucleophilic displacement of nitro groups Jackson-Meisenheimer reaction and complexes Practical significance and application of Jackson-Meisenheimer reaction Reaction potential map(RPM)... 

Meisenheimer o-complexcs 98-104 Meisenheimer reaction 97 Mercuric fulminate 462.464-469 (III/I29. 134. 135-1.36) action of liglil on 467 behaviour at low temperature 467 burning under reduced pressure 468 chemical properties of 466 (111/139-141)... 

One of the characteristic features of aromatic nitro compounds, particularly those with two or more nitro groups is their ability to react with bases and in many instances the reaction is accompanied by an intense colour. The colour had caught the attention of chemists by the late nineteenth century and initiated a considerable amount of research on the nature of the formed substances. Thus considerable literature appeared on reactions known as Janovsky or Jackson-Meisenheimer or Meisenheimer reactions which are discussed later. They are nucleophilic reactions and are not only of theoretical but also of practical importance. Thus the Janovsky reaction became an important analytical method, and reactions of di- and trinitrobenzene and their homologues with bases, are of great importance in the problem of the safety of manufacture and of the stability of these nitro compounds. 

Practical Significance and Application of Jackson-Meisenheimer Reaction... 

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