Nucleophilic attack pyridine

Ligands (NFI3, CN, pyridine) Nucleophiles (attacking L. bases) Nucleofuges (leaving L bases) Spectator anions Electron-rich pi systems H+ abstractors... 

Thiazolotriazepines (290) are prepared by reaction in cold pyridine of the product resulting from nucleophilic attack of I-hydrazinothiazole on... 

Nucleophilic Attack at Carbon or Hydrogen. Only the strongest of nucleophiles (eg, —NH2) can replace a hydrogen in pyridine. However, N-oxides and quaternary salts rapidly undergo addition, followed by subsequent transformations (12). 

Because of the increased importance of inductive electron withdrawal, nucleophilic attack on uncharged azole rings generally occurs under milder conditions than those required for analogous reactions with pyridines or pyridones. Azolium rings are very easily attacked by nucleophilic reagents reactions similar to those of pyridinium and pyrylium compounds are known azolium rings open particularly readily. 

MICHAELIS BECKER NYLEN Phosphonylation Nucleophilic attack oi lithium dialkylphosphonates on pyndkim sells to produce pyridine phosphates... 

Minisci reactions have also been applied to these compounds. formation by exposure to w-CPBA and O-methylation with Meerwein s reagent converted 54 into 55. Nucleophilic attack of the hydroxymethyl radical, generated with ammonium sulfate, provides an alternate route to 2-hydroxymethyl pyridines 56. 

Chapman and co-workers have investigated the nucleophilic displacement of chlorine in various chloronitropyridines by three pyridines. In each of these series of three compounds, an excellent correlation is observed, but, again, longer series would be extremely desirable. Similarly, the nucleophilic attack of a series of four pyridines on propylene oxide follows the Hammett equation with high pre-... 

Quatemization of the isoxazole nitrogen atom makes the ring particularly susceptible toward nucleophilic attack there is a certain analogy here with pyridine. The cleavage of the ring proceeds extremely readily in quaternary salts of isoxazole, even occurring by the action of such weak nucleophilic agents as the anions of carboxylic acids. 

In aqueous pyridine solution, most diaryl sulphoxides may be oxidized to the corresponding sulphones with (dichloroiodo)benzene in reasonable yields103. The reaction involves nucleophilic attack by the sulphoxide on the electrophilic chlorine-containing species, yielding an intermediate chlorosulphonium ion which then reacts with water producing the sulphone. If the sulphoxide is optically active, then an optically active sulphone is produced in excellent optical yield when the reaction is carried out in oxygen-18 labelled water104, as indicated in equation (33). 

The pyridine family of heteroaromatic nitrogen compounds is reactive toward nucleophilic substitution at the C(2) and C(4) positions. The nitrogen atom serves to activate the ring toward nucleophilic attack by stabilizing the addition intermediate. This kind of substitution reaction is especially important in the chemistry of pyrimidines. 

Intramolecular nucleophilic attack of a pyridine or piperidine nitrogen atom onto an electrophilic function placed in the -position of a side chain is a common way to achieve quinolizidine compounds. These reactions are systematized below on the basis of the nature of the electrophile. 

An example of this displacement between a pyridine nitrogen atom and an aryl halide is shown in Scheme 21. When 2-pyridyl acetates 138 were C-acylated with 2-halobenzoyl chlorides, the enolized products 139 resulting from the reaction suffered an intramolecular nucleophilic attack of the pyridine nitrogen atom onto the ipso-position to give benzo[c]quinolizinium salts 140 as intermediates. Loss of HC1 gas from 140 afforded benzo[c]quinolizine derivatives 141 <2002JOC2082>. 

Activation of a primary alcohol 174 by in situ mesylation and nucleophilic attack of a pyridine nitrogen atom was used in the last steps of a synthesis of cyclohexa[tf]quinolizidines 176. These compounds were obtained by direct NaBH4 reduction of intermediate pyridinium salts 175, and were proposed as tricyclic models containing the ABC-part of 8-azasteroids (Scheme 30) <1999T9269>. 

Compounds 260a-c have been studied with respect to their vulnerability to nucleophilic attack. Reactions were carried out between these compounds and pyridine, pyridine/water, DBU, and DBU/water (Scheme 25). The products formed were found to depend on the nucleophilicity and/or the basicity of the reagents used < 1998PS( 132)183>. 

Due to their electron deficient character, pyridines are susceptible to nucleophilic attack. Rudler et al. has studied the reaction of pyridines with bis(trimethylsilyl)ketene acetals <06TL4553 06TL4561>. In one instance, they examine the reaction of... 

Michael addition of (benzotriazol-l-yl)acetonitrile 557 to a,[)-unsatu rated ketones followed by heterocyclization provides new means for preparation of 2,4,5-trisubstituted pyridines. The reaction is catalyzed by bases. In the presence of secondary amines, a nucleophilic attack of amine on the CN group in adduct 556 initiates the cyclization to tetrahydropyridine 558 that subsequently eliminates water and benzotriazole to give pyridine 559. Analogously, in the presence of NaOH, pyridone 560 forms, via intermediate 561 (Scheme 88) <1997JOC6210>. 

Electronic effects. Nucleophilic attack is favoured by electron-withdrawing groups on the amide and the acyloxyl side chains. Interpolated bimolecular rate constants at 308 K for the series of para-substituted /V-acetoxy-/V-butoxybenzamides 25c, 26b-g and 26i (Table 5) gave a weak but positive Hammett correlation with a constants ip = 0.13, r = 0.86).42,43 These Sn2 reactions are analogous to those of aniline and substituted pyridines with phenacyl bromides, which have similar Arrhenius activation energies and entropies of activation in methanol (EA= 14-16 kcal mol-1, AS = — 27 to —31 calK-1 mol-1) and 4-substituted phenacyl halides afforded a similar Hammett correlation with pyridine in methanol (cr, p — 0.25).175... 

Pyridine is a jt-electron-deficient heterocycle. Due to the electronegativity of the nitrogen atom, the a and y positions bear a partial positive charge, making the C(2), C(4), and C(6) positions prone to nucleophilic attacks. A similar trend occurs in the context of palladium chemistry. The a and y positions of halopyridines are more susceptible to the oxidative addition to Pd(0) relative to simple carbocyclic aryl halides. Even a- and y-chloropyridines are viable electrophilic substrates for Pd-catalyzed reactions under standard conditions. 

During water-gas shift in pyridine solution, they isolated [PtH(py)L2]BF4, while from water-gas shift run in acetone solution, they isolated raft -[PtF[(CO)L2]BF4. The results indicated a solvent effect. That is, it was difficult to substitute coordinated pyridine with CO, but it was easier to substitute acetone with CO, via [PtH(Solvent)L2]OH + CO <-> [PtH(CO)L2]OH + Solvent. Following this important solvent-facilitated CO addition, they proposed a nucleophilic attack of OH-on the coordinated CO, via [PtH(CO)L2]OH <-> [PtH(COOH)L2]. The next step is thermal decomposition of the species, liberating C02, via the decomposition [PtH(COOH)L2] <-> [PtH2L2] + C02. CO addition was proposed to assist in decomposing the hydride to liberate H2. A more detailed description of the catalytic cycle is provided in Scheme 19. 

Another quite common reaction involving nucleophilic attack at a carbon atom of the ring is the hydrolysis of hexahydro-oxazolo[3,4- ]pyridines and tetrahydro-oxazolo[3,4-tf]pyridin-l-ones. This reaction has been known for years and is best performed under acidic conditions, respectively, producing 2-hydroxymethyl-piperidines or pipe-colic acid derivatives in good yields representative examples are collected in Table 9. Ammoniolysis of tetrahydro-oxazolo[3,4-tf]pyridin-l -ones with amino acid derivatives has also been reported and produces substituted pipecolic acid amides in good yields <2003H(61)259>. 

As depicted in Scheme 11, ylides 39 derived from 4-methyl-[l,2,3]triazolo[l,5- ]pyridine react with Michael acceptors, which, upon nucleophilic attack at C3 and ring opening, lead to nucleophilic displacement of nitrogen. The intermediate diradical led to a mixture of compounds, including alkenes and a cyclobutane derivative when methyl acrylate was used, and the indolizine 40 with methyl propiolate as the electrophile <1998T9785>. Heating 4-methyl triazolopyridine with benzenesulfonyl chloride in acetone also confirmed decomposition via a radical pathway. 

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