Pyridine 1-oxide nucleophilic reactions

In addition to their reactions with amines, Zincke salts also combine with other nitrogen nucleophiles, providing various A -substituted pyridine derivatives. Pyridine A -oxides result from the reaction with hydroxylamine, as exemplified for the conversion of Zincke salt 38 to the A -oxide 39 Reactions of Zincke salts with hydrazine, meanwhile, lead... 

Xanthobacter sp. strain Py2 may be grown with propene or propene oxide. On the basis of amino acid sequences, the monooxygenase that produces the epoxide was related to those that catalyzes the monooxygenation of benzene and toluene (Zhou et al. 1999). The metabolism of the epoxide is initiated by nucleophilic reaction with coenzyme M followed by dehydrogenation (Eigure 7.13a). There are alternative reactions, both of which are dependent on a pyridine nucleotide-disulfide oxidoreductase (Swaving et al. 1996 Nocek et al. 2002) ... 

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. 

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]. 

Perhaps the strongest evidence in favour of episulfonium ion involvement comes from the isolation of the 4-substituted 1-acetyltetrahydropyridines (137) and (138). Product (138) arises by addition of another molecule of 2-methylpropanethiol to (135). 4-Ethyl-pyridine 1-oxide on reaction with 2-methylpropanethiol, acetic anhydride and TEA yields another type of tetrahydropyridine (137). In this case TEA promotes elimination by abstraction of an ethyl proton, before 2-methylpropanethiol can attack position 6. Conversely, tetrahydropyridines are formed when R=Me, Pr or Pr1, as 2-methylpropanethiol (Scheme 78) is a better nucleophile (at C-6) than TEA is a base (at the 4-substituent). A different tetrahydropyridine (139) is obtained if the starting TV-oxide has a vacant 4-position (Scheme 79). Structural determination of compounds of this type has been greatly facilitated by the availability of 13C NMR (78JHC785). It should be remembered that while 3-substitution... 

The Hantzsch synthesis produces a reduced pyridine but there are many syntheses that go directly to pyridines. One of the simplest is to use hydroxylamine (NH2OH) instead of ammonia as the nucleophile. Reaction with a 1,5-diketone gives a dihydropyridine but then water is lost and no oxidation is needed. 

Although beyond the scope of this section, some related approaches to these compounds are worth mentioning. 2-Substituted pyridines and quinolines can be obtained in two steps from the parent compounds following nucleophilic attack by an aryllithium (e.g. 2-thienyllithium) and then oxidiation. Intramolecular oxidative coupling reactions between the 2-positions of two indole nuclei can be achieved using DDQ, in the presence of a trace of tosic acid. A very efficient route to a variety of unsymmetri-... 

Many studies on electrophilic and nucleophilic reactions of pyridazines and pyridazine N-oxides show their marked similarity to those of pyridines and their N-oxides. There are, however, some differences in nucleophilic substitution of pyridazine N-oxides, position fi to the N-oxide group being more reactive than a- and y-positions. 

Being anionic carbonyl synthons, the nitroalkanes have been explored extensively for their conversion into the corresponding carbonyl compounds. For example, the embedment of a nitroalkane onto an activated basic silica gel or the blockage of the C-protonation of nitronate with a protonated concave pyridine. The reaction under the latter condition is called the soft Nef reaction. In addition, the introduction of a y-trimethylsilyl group is proved to smooth the Nef reaction. Moreover, when a primary nitroalkane is treated with nitrite/acetic acid, a carboxylic acid is resolved. Furthermore, the oxidative Nef reaction has successfully converted the nitro cyclohexadienes into the substituted phenols via a nucleophilic addition. 

Chloropyridine serves as a raw material in the production of pyridine-thiones these are manufactured by the reaction of chloropyridine with H2O2 or other peroxides, followed by a nucleophilic reaction of the N-oxide with sodium hydrogen sulfide to produce the thiol. The zinc salt is used as an active ingredient (anti-dandruff agent) in hair shampoos. 

Addition of an ammonia source to pyrylium salts readily affords pyridine derivatives and provides a good method for the preparation of the pyridine moiety if the corresponding pyrylium salt is accessible. The carbon oxygen double bond present in the pyrylium salt is an oxonium ion however, owing to aromatic stabilization they are easily formed by a variety of methods. The reactivity of pyrylium salts toward nucleophiles makes them useful reagents for the preparation of structurally diverse heterocyclic compounds. Thus pyrylium salts afford pyridines by reaction with ammonia, pyridine-A -oxides by reaction with hydroxylamine and pyridinium salts by reaction with primary amines. 

Ample opportunities are opened with synthesis of trifluoromethylated azines via oxidative nucleophilic substitution of hydrogen by trifluoromethyl carbanions [175], This pathway to the synthesis of trifluoromethylazines includes reaction of quatemization of azines 283 by p-methoxybenzylbromide (PMB) (284) to obtain salts 285. Further KF is added to reaction mixture of salt 285 and CF3Si(CH3)3 to generate anion 286. Regioselective trifluoromethylation results in formation of 1,2-dihydropyridines 287 which then have been oxidized by action CAN to get appropriate trifluoromethylazines 288 (Table 4) [ 175] (Scheme 85). Regioselectivity of the reactions is determined by the nature of substituent at pyridine s cycle. So in case of an ether of nicotinic acid and 3-benzoylpyridine the mixture of 2-and 6-trifluoromelhylpyridines are formed (Table 5). 

When pyridine 1-oxide reacts with bromine, sodium acetate and acetic anhydride, 3,5-dibromopyridine 1-oxide is formed . / -Nitrobenzoyl chloride and silver nitrate produce small yields of 3-nitro- and 3,5-dinitro-pyridine l-oxide . These reactions probably involve nucleophilic addition, followed by electrophilic substitution, and the first step can be represented as occurring at C(4), though not with any compelling reason ... 

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