Pyridines ipso substitution

Pyridine, 6-cyano-l,2-dihydro-thermal dimerization, 2, 370 Pyridine, 2-cyanomethyl-tautomerism, 2, 159 Pyridine, 4-cyanomethyl-tautomerism, 2, 159 Pyridine, 2-cyano-2,3,4,5-tetrahydro-metallation, 2, 387 Pyridine, 2,5-diacetyl-ipso substitution, 2, 301 Pyridine, 3,5-diacetyl-l,4-dihydro-Hantzsch synthesis, 2, 482 Pyridine, 4-dialkylamino-as acylation catalysts, 2, 34 Pyridine, 2,2-dialkyl-l,2-dihydro-... 

In these reaetions, the most reliable mechanism is considered to involve the initial metal-coordination at the nitrogen atom of the pyridine ring and the subsequent attack of an alkyl or aryl anion at the most probable cationic sites on the ring, namely, the 2- and/or 4-position of the ring. If a 2-halogen substituted pyridine is used, the nucleophilic anion attacks the 6-position. Thus, the addition is a more prefered reaction than the ipso-substitution as shown in reaction (29). The substitution of amide or phenyl-... 

Usually, ipso substitution of the diazo moiety is observed but, particularly when the substrate is substituted by electron-withdrawing groups (N02, CF3) and the nucleophile Nu is not very reactive, the reaction does not proceed regiospecifically and ArNu is obtained as an isomeric mixture. Deuterium is also incorporated when the reaction is performed in a deuterium fluoride/pyridine mixture.15a g 17 These results can be explained by [l,2]-hydrogen shifts in... 

Z)-Benzyl-3-(2-halophenyl)-3-hydroxy-2-(pyridin-2-yl)acrylates 664 can undergo competitive intramolecular ipso-substitutions to form the intermediates 665 and 666. The irreversible elimination of benzyl chloride from intermediate 666 affords 4-hydroxy-3-(2 -pyridyl)coumarins in high yield (Scheme 158) <2001CC639>. 

The preceding discussion has, by implication, suggested that radical ipso-substitution reactions with heteroaromatic bases are rare. A few examples have been uncovered. For example, irradiation of 2-cyanoquinoline in acidic ethanol led to hydroxyethylation of the heterocycle with loss of the cyano-group (Scheme 24) <73BCJ942, 74BCJ942>. Similarly, 2-cyanopyridine has been transformed into 2-(l-hydroxyethyl)-pyridine in 30% yield by this method when run under conditions of high dilution <75CC241>. 

It is interesting to contrast this substitution reaction with a complementary method for achieving the hydroxyalkylation of pyridines and quinolines developed by Minisci et al. <85T617>. They found that addition of hydroxylamine-(9-sulfonic acid to an acidic solution of 4-cyanopyridine in methanol containing catalytic iron(Il) sulfate, gave 2-(hydroxymethyl)-4-cyanopyridine 70 on work-up (Scheme 25). No products derived from ipso-substitution of the cyano-fiinction were observed. 

A sulfinyl or sulfonyl group at the 2- or 4-position of a pyridine ring can be displaced by nucleophiles (i.e. alkoxides, thiolates, and cyanide) to afford the corresponding ipso substitution products. Similarly, 2-halo-6-methylsul-finyl- or 2-halo-6-methylsulfonylpyridines react with nucleophiles to give... 

When aminopyridine N-nitroso derivatives 21 and 23 were treated with hydroxide or methoxide, ipso substitution occurred at the 2-position to give nitropyridines 22 and 24 (85MI2). Reactions of 3-azido-2-nitropyridine (25) and 4-azido-3-nitropyridine (27) with nucleophiles were studied. Pyridine 25 and sodium hydroxide gave pyridone 26. Morpholine and pyridine 27 gave the 3,4-disubstituted pyridine 28 (83KGS373). Treatment of 2-cyano-3,5-dimethyl-4-nitropyridine with sodium methoxide effects substitution at the... 

The first pincer ligand bearing NHC moieties 1 was presented by Peris and Crabtree in 2001 [9] (Figure 9.1). The bisimidazolium salt precursor of this neutral CNC ligand with a pyridine backbone 1 can be synthesized by a nucleophilic ipso substitution of 2,6-dichloro- or dibromopyridine. With this strategy, also... 

The 3-pyridyl O-carbamate affords, under the sec-BuLi/TMEDA conditions, only 4-substituted products. A reinvestigation of LDA metalation (85JOC5436) has shown that high-yield conversion of 320 into the 4-TMS (319) and 2,4-bis-TMS (321) derivatives can be effected (Scheme 97) [90UP1]. Furthermore, LiTMP metalation of 319 followed by electrophile quench leads to derivatives 322, thus demonstrating the TMS protection route to 2-substituted 3-oxygenated pyridines. Another, potentially useful result is the 2-position selective ipso carbodesilylation of 321 with benzoyl chloride, yielding 323. 

In their early studies, Pinhey et al. showed that, when the reaction of a phenol with an aryllead triacetate is performed in the presence of pyridine, only the C-arylated dienones 35 and 36 are formed in a nearly quantitative yield (90% ortho para ratio of 4 1) (Equation (38)). Under their classical conditions (phenol organolead triacetate base in a ratio 1 1 3), the reaction of methylated phenols only proceeded in high yield when both ortho-positions are substituted. There is a preference for attack ipso to a methoxyl group compared to a methyl group.45 453... 

Although pyridine is resistant to electrophilic aromatic substitution, it is susceptible to nucleophilic aromatic substitution. The reaction of 2-bromopyridine (44) and ammonia, for example, leads to 2-aminopyridine, 46. This is a nucleophilic aromatic substitution reaction (see Chapter 21, Section 21.10), where NHg attacks the ipso carbon to generate a carbanionic intermediate (45), which loses bromine to give 46. Pyridine (10) also reacts directly with sodium amide (NaNHg) at 100°C to give 46 in what is known as the Chichibabin reaction, after Aleksei E. Chichibabin (Russia 1871-1945). 

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