Electrophilic Nature of the Oxidant

Electron-withdrawing groups strongly reduce the rate of hydroxylation of the aromatic nuclei, indicating the electrophilic nature of the oxidant species. Accordingly, nil or negligible yields were reported for chlorobenzene, nitrobenzene, ben-zonitrile, benzaldehyde, and benzoic acid [2]. In a recent patent the hydroxylation of 1,4-dichlorobenzene, based on unusually large amounts of catalyst, was claimed. Yields of 2,5-dichlorophenol were not indicated [26]. 

The reactivity of the individual O—P insecticides is determined by the magnitude of the electrophilic character of the phosphoms atom, the strength of the bond P—X, and the steric effects of the substituents. The electrophilic nature of the central P atom is determined by the relative positions of the shared electron pairs, between atoms bonded to phosphoms, and is a function of the relative electronegativities of the two atoms in each bond (P, 2.1 O, 3.5 S, 2.5 N, 3.0 and C, 2.5). Therefore, it is clear that in phosphate esters (P=0) the phosphoms is much more electrophilic and these are more reactive than phosphorothioate esters (P=S). The latter generally are so stable as to be relatively unreactive with AChE. They owe their biological activity to m vivo oxidation by a microsomal oxidase, a reaction that takes place in insect gut and fat body tissues and in the mammalian Hver. A typical example is the oxidation of parathion (61) to paraoxon [311-45-5] (110). 

The triflic acid catalyzed electrophilic hydroxylation of aromatics with BTSP gives the corresponding phenols in high yields without apparent polyhydroxylation or secondary oxidation. Thus, treatment of CeHe with CF3SO3H followed by BTSP gave 11% PhOH. The isomer distributions are in accord with the electrophilic nature of the reaction. The observed ortho/para ratio in the case of toluene agrees with the expected trends (Scheme 4 and Table ll) . 

A comparison of the isoelectronic CpFe(CO)2R an CpCr(NO)2R is also noteworthy. When R = CHaPh or Ph, the latter system inserts SO2 much more rapidly than the former (61, 71). This may be a result of the lower formal oxidation state of chromium(O) than of iron(II) and is consistent with an electrophilic nature of the insertion. 

The first synthesis of pentaphyrin was reported by Gossauer in 1983. He used an HBr-catalyzed 2 + 3 MacDonald-type condensation between the diformyl tripyrrane 6.29 and the a-free dipyrrylmethane derivative 6.32 to establish the basic macrocyclic framework. Oxidation with chloranil then gave pentaphyrin 6.35 in 31% overall yield (Scheme 6.4.1). Subsequent to this original disclosure, syntheses of pentaphyrins with various other peripheral substituents appeared in the literature (e.g., 6.38 and 6.39). They were all made using this same general procedure." Interestingly, it was found that pentaphyrins could not be prepared when the nucleophilic and electrophilic nature of the reactant dipyrrylmethane and tripyrrane (the 2 and 3 components, respectively) were reversed. This became evident when the diacid tripyrrane 6.38 and the diformyl dipyrrylmethane 6.39 were reacted under conditions identical to those used to prepare pentaphyrin 6.35. Here, only porphyrins, and not pentaphyrins, were obtained (Scheme 6.4.2). " ... 

The method can also be applied to the conversion of 4-chloropyridine (49) to pyridine-4-sulfonic acid (50) (Scheme 28). In compound (49), the chlorine atom is activated to nucleophilic attack by the electron-withdrawing nitrogen atom. Scheme 28 is a useful synthetic sequence since direct sulfonation of pyridine only yields the 3-sulfonic acid as a consequence of the electrophilic nature of the nitrogen atom. Sulfonic acids can also be obtained by oxidation of sulfides, disulfides and sulfinic acids. The introduction of a sulfonic acid group into an organic molecule provides a useful method of increasing the aqueous solubility of the compound. Many sulfonic acids as their sodium salts are... 

Nucleophilic Addition. The electrophilic nature of the a-position of this inner salt makes it prone to nucleophilic addition. Treatment with Ruppert s reagent (CFsSiMes) gives a 2-trifluoromethyl-dihydropyridine derivative in a 79% yield with complete regioselectivity (eq 6). This dihydropyridine intermediate can be subsequently oxidized to a 2-trifluoromethylated inner salt upon treatment with DDQ in a 60% yield. This overall process features a net 2-trifluoromethylation of the parent inner salt. 

Forming a metal complex may serve to activate NO toward either nucleophilic or electrophilic attack depending on the nature of the metal complex and its oxidation state. Of particular interest biologically are the reactions with nucleophiles since this may well be a mechanism for thionitrosyl formation (e.g. Eq. (55)) as well as for reductively labiliz-ing metals in insoluble matrices like ferritin. 

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