Pyridine ring reactivity

The 5-position is the preferred site for sulfonation (58. 392). This position is more reactive than any of the pyridine ring in. V-[pyridyl-(2)]-thiazolyl-(2)-amine (178) (132, 382, 383). 

Carbon Substituents. Alkyl groups at positions 2 and 4 of a pyridine ring are more reactive than either those at the 3-position of a pyridine ring or those attached to a benzene ring. Carbanions can be formed readily at alkyl carbons attached at the 2- and 4-positions. This increased chemical reactivity has been used to form 2- and 4-(phenylpropyl)pyridines, eg, 4-(3-phenylpropyl)pyridine [2057-49-0] (21) (24). 

Reactions. Quinoline exhibits the reactivity of benzene and pyridine rings, as weU as its own unique reactions. 

The electrophilic substitution of thiophene is much easier than that of benzene thus, thiophene is protonated in aqueous sulphuric acid about 10 times more rapidly than benzene, and it is brominated by molecular bromine in acetic acid about 10 times more rapidly than benzene. Benzene in turn is between 10 and lo times more reactive than an uncharged pyridine ring to electrophilic substitution. 

For pyridine, the reactivity toward electrophilic substitution is 3 > 4, 2. The ring nitrogen acts as a strongly destabilizing internal electron-withdrawing substituent in the 2- and 4-intermediates. The nitrogen also deactivates the 3-position, but less so than the 2- and 4-positions. 

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

From the relative reactivities, together with the isomer ratios for the phenylation of pyridine, it is possible to calculate the reactivity of each position in the pyridine ring compared with that of any one position in benzene (the partial rate factor). Thus, using the value of 1.04 for the relative reactivities obtained by Augood et al and the isomer ratios (2-, 58 3-, 28 4-, 14) obtained by Dannley and Gregg, the partial rate factors for the three positions in pyridine are 2-, 1.8 3-, 0.87 4-, 0.87. It is doubtful, however, whether much... 

Bromination of 136 in methanol gave the 3-bromo derivative, identical with the product of Sandmeyer reaction of the 3-diazonium salt. When the reactive 3-position was blocked, electrophilic bromination would not take place (66JOC265). Chlorination appears to occur by addition [83AHC(34)79], and perhalides are known [84MI25 90AHC(47)1]. Activating substituents are able to induce some bromination in the pyridine ring. 

Compared with monocyclic aromatic hydrocarbons and the five-membered azaarenes, the pathways used for the degradation of pyridines are less uniform, and this is consistent with the differences in electronic structure and thereby their chemical reactivity. For pyridines, both hydroxylation and dioxygenation that is typical of aromatic compounds have been observed, although these are often accompanied by reduction of one or more of the double bonds in the pyridine ring. Examples are used to illustrate the metabolic possibilities. 

Methyl substituents on the pyridine ring had a profound impact on the reactivity of the pyridine ring. 2,6-Lutidine did not react to any appreciable extent on Ni(100) [12]. The infrared spectrum of 2,6-lutidine showed no C=C stretches and ring vibrations, but did show CH... 

The methyl groups on the pyridine ring result in a major difference in the reactivity of lutidines. In 3,5-lutidine the methyl groups act as electron donors tending to increase the stability of the tt-bonds, and activating the ring for electrophilic attack at the a-positions. The MOs in 3,5-lutidine show the it-levels pushed to lower energy... 

Isoxazolo[2,3-4]pyridines 44, isothiazolo[2,3-4]pyridines 46, and their fully saturated derivatives 45 and 47 (Scheme 16) were discussed in CHEC(1984) <1984CHEC(6)613> and CHEC-II(1996) <1996CHEC-II(8)249>. Very little information was available on the isothiazolo[2,3- ]pyridine ring system while most of the informations given on the oxygenated parent, isoxazolo[2,3- ]pyridines, concerned the fully saturated system. Careful examination of the literature clearly shows that the situation did not change much almost no references have been reported on isothiazolo[2,3- ]pyridines and most of the work done in the last decade concerns the synthesis and reactivity of hexahydro-isoxazolo[2,3- ] pyridines 45. Therefore, this chapter will briefly describe the new reactions of fully conjugated systems and will focus on the partially/completely saturated derivatives. 

Dipolar addition of mesitylene nitrile oxide with 4,7-phenanthroline 159 gave a 2 1 adduct 160 with a very low yield (Equation 19), the dearomatization of the pyridine ring giving rise to a more reactive double bond which, in turn, underwent cyclization <1998T9187>. 

The ring closure of 3-pyridylaminomethylenemalonates may lead to 1,5-naphthyridine or 1,7-naphthyridine, depending on which position of the pyridine ring (position 2 or 4) is involved in the cyclization (Scheme 45). Due to the higher reactivity of position 2 of 3-aminopyridine derivatives... 

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