Pyridines protonic salts

Of more preparative value are the reactions of nucleophilic radicals, such as HOCHa and RaNCO, which can be easily generated under mild conditions, for example HOCH2 from ethylene glycol by persulfate oxidation with silver nitrate as catalyst. These substitutions are carried out on the pyridine protonic salt, which provides both increased reactivity and selectivity for an a-position the process is known as the Minisci reaction (cf. 3.4.1). It is accelerated by electron-withdrawing substituents on the ring. 

Very selective monosubstitution can also be achieved by the ingenious use of an A -methoxy quaternary salt, in place of the usual protonic salt. Here, re-aromatisation is the result of loss of methanol, leaving as a product a much less reactive, neutral pyridine. ... 

Pyridine itself can be converted into 3-nitropyridine only inefficiently by direct nitration, even with extremely vigorons conditions, however a couple of ring methyl groups facihtate electrophilic substitution snfficiently to allow nitration both collidine (2,4,6-trimethylpyridine) and its M-methyl quaternary salt are nitrated at similar rates under the same conditions, showing that the former reacts via its A -protonic salt. Steric or/and inductive inhibition of M-nitration allows C-3-substitution using nitronium tetrafluo-roborate an example is the nitration of 2,6-dichloropyridine or of 2,6-difluoropyridine using tetramethyl-ammoninm nitrate with trifluoromethansulfonic anhydride. ... 

Activating substitutents, i.e. groups which can release electrons either inductively or mesomerically, make the electrophilic substitution of pyridine rings to which they are attached faster, for example 4-pyridone nitrates at the 3-position via the O-protonated salt. In order to understand the activation, it is helpful to view the species attacked as a (protonated) phenol-like substrate. Electrophilic attack on neutral pyridones is best visualised as attack on an enamide. Dimethoxypyridines also undergo nitration via their cations, but the balance is often delicate, for example 2-aminopyridine brominates at C-5, in acidic solution, via the free base. ... 

Acid catalysis requires a contribution by the Mg ion, which is thought to induce a conformational change that brings the acidic group into a catalytically competent position. Removal of Mg has little effect on the hydrolysis of pyridin-ium salts but lowers the rate of hydrolysis of O-glycosides. The metal ion, as revealed by experiments with Mn " as an NMR probe, is not coordinated to the sugar. It is positioned at a distance of 9 A from the methyl protons of the Me-S-galactoside bound in the active site (33). 

The suggested imino-tautomeric form of the compound studied is also indicated by the H-NMR spectra. The chemical shift for the pyridine proton signals of 4-amin-opyridine belonging to C(3)H and C(2)H are at 6.92 (2H, q) ppm and 8.04 (2H, q) ppm, respectively. The spectra in the solutions of the salts show shifting of the doublet peaks at 7.18 ppm and 8.23 ppm. The data indicate a redistribution of the electron density, a result that can be compared to the analogous data of the 4-aminopyridine/ D2SO4 systan, characterized by pairs of doublets at 8.44 ppm and 7.22 ppm. The... 

As early as 1889 Walker (320), using samples of thiazole, 2,4-dimethylthiazoie, pyridine, and 2,6-dimethylpyridine obtained from Hantzsch s laboratory, measured the electrical conductivity of their chlorhydrates and compared them with those of salts of other weak bases, especially quinoline and 2-methylquinoline. He observed the following order of decreasing proton affinity (basicity) quinaldine>2,6-dimethyl-pyridine>quinoline>pyridine>2,4-dimethylthiazole> thiazole, and concluded that the replacement of a nuclear H-atom by a methyl group enhanced the basicity of the aza-aromatic substrates. 

Pyridinethiones acylation, 2, 357 alkylation, 2, 357 aromaticity, 2, 148 protonation, 2, 357 tautomerism, 2, 356 Pyridine-2-thiones aromaticity, 2, 156 basicity, 2, 157 oxidation, 2, 357 N-oxide, sodium salt biocide, 1, 399 synthesis, 2, 360... 

Dihydro- and 1,4-dihydro derivatives are formed as intermediates in the reduction of quaternary pyridine salts and their homologues with sodium borohydride or formic acid. A proton is added to the present enamine grouping and the formed immonium salts are reduced to the l-methyl-l,2,5,6-tetrahydropyridine derivatives (157) and to completely saturated compounds (158) (254) (Scheme 14). 

The Zincke reaction is an overall amine exchange process that converts N- 2,A-dinitrophenyl)pyridinium salts (e.g, 1), known as Zincke salts, to iV-aryl or iV-alkyl pyridiniums 2 upon treatment with the appropriate aniline or alkyl amine. The Zincke salts are produced by reaction of pyridine or its derivatives with 2,4-dinitrochlorobenzene. This venerable reaction, first reported in 1904 and independently explored by Konig, proceeds via nucleophilic addition, ring opening, amine exchange, and electrocyclic reclosure, a sequence that also requires a series of proton transfers. By... 

CaveU and Chapman made the interesting observation that a difference exists between the orbital involved in the quatemization of aromatic nitrogen heterocycles and aromatic amines, which appears not to have been considered by later workers. The lone pair which exists in an sp orbital of the aniline nitrogen must conjugate, as shown by so many properties, with the aromatic ring and on protonation or quatemization sp hybridization occurs with a presumed loss of mesomerism, whereas in pyridine the nitrogen atom remains sp hybridized in the base whether it is protonated or quaternized. Similarly, in a saturated compound, the nitrogen atom is sp hybridized in the base and salt forms. 

In this solvent the reaction is catalyzed by small amounts of trimethyl-amine and especially pyridine (cf. 9). The same effect occurs in the reaction of iV -methylaniline with 2-iV -methylanilino-4,6-dichloro-s-triazine. In benzene solution, the amine hydrochloride is so insoluble that the reaction could be followed by recovery. of the salt. However, this precluded study mider Bitter and Zollinger s conditions of catalysis by strong mineral acids in the sense of Banks (acid-base pre-equilibrium in solution). Instead, a new catalytic effect was revealed when the influence of organic acids was tested. This was assumed to depend on the bifunctional character of these catalysts, which act as both a proton donor and an acceptor in the transition state. In striking agreement with this conclusion, a-pyridone is very reactive and o-nitrophenol is not. Furthermore, since neither y-pyridone nor -nitrophenol are active, the structure of the catalyst must meet the conformational requirements for a cyclic transition state. Probably a concerted process involving structure 10 in the rate-determining step... 

UV spectrum changes dramatically. The salt causes maxima at 251 (4.16), 286 (4.16), 387 (3.56), and 473 (3.37) nm. NMR data for a sample in CF3COOD were presented. It is interesting to note that the nonmethylated derivatives of 130 and 131 are present in solution above pH 6.5 as betaines, forming a protonated pyridine ring and an olate group (91MI3). 

In another investigation (Loewenschuss et al., 1976) dediazoniation was studied in TFE and in acetonitrile in the presence of pyridine. There is UV and NMR evidence for the formation of a diazopyridinium cation in addition, -CIDNP absorption and emission signals were observed. Systems containing diazonium salts and pyridine are important in industrial chemistry, as pyridine is used as a proton acceptor in the diazo coupling reaction (see Sec. 12.8) in a considerable number of syntheses of azo dyes. At the same time pyridine has an unfavorable effect on the yield because of the competing homolytic dediazoniation. 

Carbene complexes have also been prepared by transmetallation reactions. Lithiated azoles react with gold chloride compounds and after protonation or alkylation the corresponding dihydro-azol-ylidene compounds, e.g., (381) or (382), are obtained.22 9-2264 Silver salts of benz-imidazol have also been used to obtain carbene derivatives.2265 Mononuclear gold(I) carbene complexes also form when trimeric gold(I) imidazolyl reacts with ethyl chlorocarbonate or ethyl idodate.2266,2267 The treatment of gold halide complexes with 2-lithiated pyridine followed by protonation or alkylation also yields carbene complexes such as (383).2268 Some of these carbene complexes show luminescent properties.2269-2271... 

Nitrogen-containing heterocycles are sometimes basic enough to protonate and form salts in acidic conditions and this leads to substantial changes in chemical shifts of their protons - see Spectrum 5.9 (pyridine alone, pyridine + DC1)... 

In practical terms, it is invariably a nitrogen atom that is protonated in salt formation. This always leads to a downfield shift for protons on carbons both alpha and beta to the nitrogen concerned. In alkyl amines, the expected shifts would be about 0.7 and 0.3 ppm respectively. Remember that some heterocyclic compounds (e.g., pyridine) contain nitrogen atoms that are basic enough to protonate and comparable downfield shifts can be expected (Spectrum 5.9). 

There is nothing unusual about the acidic behavior of ammonium salts. In fact, any protonated amine can function as a proton donor. Because of this, many amine salts have been used as acids in synthetic reactions. If the chlorides are used, the amine salts are known as amine hydrochlorides. One of the earliest amine hydrochlorides studied with regard to its behavior as an acid is pyridine hydrochloride (pyridinium chloride), C5H5NH+C1. In the molten state, this compound undergoes many reactions of the type just shown. 

Many years ago, L. F. Audrieth studied numerous reactions of amine hydrochloride salts. These compounds contain a cation that is a protonated amine that can function as a proton donor. Consequently, the molten salts are acidic and they undergo many reactions in which they function as acids. This behavior is also characteristic of ammonium chloride as well as pyridine hydrochloride (or pyridinium... 

When treated with DBU at elevated temperature, l-[(benzotriazol-l-yl)methyl -2-aminopyridine salts 741 eliminate rather the N-H proton than the C-H one. Intermediates 742 can be trapped with aromatic aldehydes to create betaines 743. The consecutive cyclocondensation and elimination of benzotriazole results in formation of imidazolo[l,2-rz]pyridines 744 in good yields (Scheme 117) <2000JOC9201>. Aldehydes with enolizable a-protons fail to give bicyclic systems 744, producing corresponding enamines instead. 

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