Pyridines with nucleophiles

In the past year, reviews on 1,8-naphthyridines, perimidines, polyazaphen-anthrenes, 3-azabicyclo[3.3.1]nonanes, and 1,2- and 2,1-benzothiazines have appeared. Reviews on specialist aspects of pyridine chemistry are devoted to the reactions of newly available pyridines, a,a -disubstituted pyridines, the reactions of pyridines with nucleophiles, the electrochemistry of IjT-disubstituted 4,4 -bipyridinium ions (the viologens such as paraquat), dihydropyridines, and 4-aryl-dihydropyridines (a new class of calcium antagonists). Reviews have been published on the cyclization of oximes and amides to quinolines and isoquinolines, quinoline- and isoquinoline-diones, benzo[fl ]- and benzo[c]-quinolizinium ions, azachrysene preparation, quinazolines with plant-growth-regulating and biocidal activities, quinazolines in pharmaceutical research, isotopic hydrogen exchange in... 

Scheme 13.15 Relative rates for the alkylation of protonated poro-substituted pyridines with nucleophilic radicals.

Chemical Properties. The presence of both a carbocycHc and a heterocycHc ring faciUtates a broad range of chemical reactions for (1) and (2). Quaternary alkylation on nitrogen takes place readily, but unlike pyridine both quinoline and isoquinoline show addition by subsequent reaction with nucleophiles. Nucleophilic substitution is promoted by the heterocycHc nitrogen. ElectrophiHc substitution takes place much more easily than in pyridine, and the substituents are generally located in the carbocycHc ring. 

In 1904, Zincke reported that treatment of Al-(2,4-dinitrophenyl)pyridinium chloride (1) with aniline provided a deep red salt that subsequently transformed into A-phenyl pyridinium chloride 5 (Scheme 8.4.2). Because the starting salt 1 was readily available from the nucleophilic aromatic substitution reaction of pyridine with 2,4-dinitrochlorobenzene, the Zincke reaction provided access to a pyridinium salt (5) that would otherwise require the unlikely substitution reaction between pyridine and... 

Quinoxalines undergo facile addition reactions with nucleophilic reagents. The reaction of quinoxaline with allylmagnesium bromide gives, after hydrolysis of the initial adduct, 86% of 2,3-diallyl-l,2,3,4-tetrahydroquinoxaline. Quinoxaline is more reactive to this nucleophile than related aza-heterocyclic compounds, and the observed order of reactivity is pyridine < quinoline isoquinoline < phenan-thridine acridine < quinoxaline. ... 

Replacement of one of the benzene rings in a fenamic acid by pyridine interestingly leads to a compound which exhibits antiliypertensive rather than antiinflammatory activity. Preparation of this agent starts with nucleophilic aroniatic substitution of anthranilic acid (8) on 4-chloropyri-dine. The product (9) is converted to its acid chloride (10), and this is condensed with piperidine. There is thus obtained ofornine (11) f31. 

Steric factors and especially hindered rotations may change the pATa of an acid by up to two pAfa units as has been found for 2,6-disubstituted pyridines 2,6-di-t-butylpyridine [70k] is an unusual (Kanner, 1982) non-nucleophilic base which has a surprisingly low pKa value. When [70k] is compared to other 2,6-dialkylsubstituted pyridines [70] it is found to be the only disubstituted pyridine with a smaller pKa than pyridine itself (see Table 29). The exceptional behaviour of [70k] has been investigated intensively... 

Nucleophilic reactivity toward Pt(II) complexes may be conveniently systematized via linear free energy relationships established between reactions of trans Ptpy2Cl2 (py = pyridine) with various nucleophiles and reactions of other Pt(II) complexes with the same nucleophiles. First, each nucleophile is characterized by a nucleophilicity parameter, derived from its reactivity toward the common substrate, trans Ptpy2Cl2. Reactivity toward other Pt(II) substrates is then quite satisfactorily represented by an equation of the form (21), wherein ky is the value of in the reaction with nucleophile Y... 

Bis l,2-(trifluoromethanesulfonlyloxy)tetramethyldisilane is a stable and reactive compound towards different nucleophiles (14). It reacts rapidly with pyridine forming mono and (at a 1 2 ratio) disalts with pyridine. With secondary amines this compound forms the corresponding disilyldiamine. Dialkoxydisilanes were prepared in good yields in the reaction with different alcohols ... 

Nitroenamines and related compounds have been used for synthesis of a variety of heterocyclic compounds. Rajappahas summarized the chemistry of nitroenamines (see Section 4.2).140 Ariga and coworkers have developed the synthesis of heterocycles based on the reaction of nitropyridones or nitropyrimidinone with nucleophiles. For example, 2-substituted 3-nitro-pyridines are obtained by the reaction of l-methyl-3,5-dinitro-2-pyridones with ketones in the presence of ammonia (Eq. 10.82).141... 

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... 

Nucleophilic Trapping of Radical Cations. To investigate some of the properties of Mh radical cations these intermediates have been generated in two one-electron oxidant systems. The first contains iodine as oxidant and pyridine as nucleophile and solvent (8-10), while the second contains Mn(0Ac) in acetic acid (10,11). Studies with a number of PAH indicate that the formation of pyridinium-PAH or acetoxy-PAH by one-electron oxidation with Mn(0Ac)3 or iodine, respectively, is related to the ionization potential (IP) of the PAH. For PAH with relatively high IP, such as phenanthrene, chrysene, 5-methyl chrysene and dibenz[a,h]anthracene, no reaction occurs with these two oxidant systems. Another important factor influencing the specific reactivity of PAH radical cations with nucleophiles is localization of the positive charge at one or a few carbon atoms in the radical cation. 

Aryl(trimethylsiloxy)carbenes. Acylsilanes (153) undergo a photoinduced C —> O silyl shift leading to aryl(trimethylsiloxy)carbenes (154).73,74 The carbenes 154 can be captured by alcohols to form acetals (157) 73 or by pyridine to give transient ylides (Scheme 29).75 LFP of 153 in TFE produced transient absorptions of the carbocations 155 which were characterized by their reactions with nucleophiles.76 The cations 155 are more reactive than ArPhCH+, but only by factors < 10. Comparison of 154 and 155 with Ar(RO)C and Ar(RO)CH+, respectively, would be of interest. Although LFP was applied to generate methoxy(phenyl)carbene and to monitor its reaction with alcohols,77 no attempt was made to detect the analogous carbocation. 

Relative rates of some prototypical carbenes, obtained by Stem-Volmer methods, are listed in Table 2. Although many of these carbenes have triplet ground states, reaction with nucleophiles Y occurs prior to spin equilibration. Most often, ylide formation with solvent molecules was analysed in terms of Eq. 3. The pyridine-ylide served as the probe for 154. 

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... 

For Negishi reactions in which the pyridines are nucleophiles, the pyridylzinc reagents are usually prepared from the corresponding halopyridines [6, 20, 21]. An excess of 2-chlorozincpyridine /V-oxide (26), arising from 2-bromopyridine N-oxide hydrochloride (25), was coupled with vinyl triflate 27 in the presence of Pd(Ph3p)4 to furnish adduct 28 [20]. Recently, an efficient Pd-catalyzed cyanation of 2-amino-5-bromo-6-methylpyridine (29) using zinc cyanide has been reported to afford pyridyl nitrile 30 [22]. 

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. 

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