Nitric oxide electrophilic attack

Bromine in chloroform and bromine in acetic acid are the reagents used most often to brominate pyrazole. When nitric acid is used as a solvent, both bromine and chlorine transform pyrazoles into pyrazolones (Scheme 24). Thus 3-methyl-l-(2,4-dinitrophe-nyOpyrazole is brominated at the 4-position (309). The product reacts with chlorine and nitric acid to give the pyrazolone (310). The same product results from the action of bromine and nitric acid on (311). The electrophilic attack of halogen at C-4 is followed by the nucleophilic attack of water at C-5 and subsequent oxidation by nitric acid. 

These compounds are less common than indole (benzo[ ]pyrrole). In the case of benzo[i>]furan the aromaticity of the heterocycle is weaker than in indole, and this ring is easily cleaved by reduction or oxidation. Electrophilic reagents tend to react with benzo[Z ]furan at C-2 in preference to C-3 (Scheme 7.21), reflecting the reduced ability of the heteroatom to stabilize the intermediate for 3-substitution. Attack in the heterocycle is often accompanied by substitution in the benzenoid ring. Nitration with nitric acid in acetic acid gives mainly 2-nitrobenzo[Z ]furan, plus the 4-, 6- and 7-isomers. When the reagent is in benzene maintained at 10 °C, both 3- and 2-nitro[ ]furans are formed in the ratio 4 1. Under Vilsmeier reaction conditions (see Section 6.1.2), benzo[Z ]furan gives 2-formylbenzo[6]furan in ca. 40% yield. 

The positively charged nitronium ion is isoelectronic with carbon dioxide and is a linear molecule. It is a strong oxidant with a reduction potential of + 1.6 V at pH 7.0, favoring electrophilic attack. Nitronium ion is the active agent in fuming nitric acid (a caustic mixture of sulfuric and nitric acids), where the nitric acid is effectively dehydrated to give nitronium ion. 

Electrophiles attack xanthene at C-2 and sometimes also at C-7 when conditions are sufficiently vigorous. Nitric acid simultaneously oxidizes xanthene to the xanthone and thus gives 2-nitroxanthone. Friedel-Crafts acetylation of xanthene gives either 2-acetyl- or 2,7-diacetylxanthene according to the temperature (0 or 18 °C) and the proportion of acetyl chloride (74BSF2963). 

The electrophilic attack of nitric oxide on a bent nitrosyl is now realized to be the path by which hyponitrite-bridged Co species are formed. Reaction (93) was known since the time of Werner (217), but the black and red isomers of [Co(NO)(NH3)5]2+ obtained from this reaction defied definitive characterization for many years. It has now been established that the black isomer is a mononuclear, octahedral complex of Co(III) and NO- (218) while the red isomer is a hyponitrite bridged system containing two Co(III) ions (219). 

As has already been mentioned in Section II, pyridine A-oxide is much more susceptible to electrophilic attack than is pyridine. Nitration with fuming nitric acid in sulfuric acid at 90° or with potassium nitrate or nitric acid in fuming sulfuric acid at 100-130° gives up to 90% yields of 4-nitropyridine A-oxide together with a small amount of the 2-isomer (formation of 2-isomer reported by... 

Very interesting transformations were reported in terminal alkynes RC=CH (R = alkyl, aryl, alkoxy, carboxylate, etc.). They react readily with nitric acid, in aqueous nitromethane (1 1) and in the presence of catalytic amounts of tetra-butylammonium tetrachloroaurate to give 3,5-disubstituted isoxazoles 15 in 35% to 50% isolable yield (92). The reaction might proceed via a nitrile oxide intermediate by attack of an electrophile (AuCh or H+) and of a nucleophile (N02 ) on the triple bond to form a vinyl nitrite, which is converted to a nitrile oxide by the action of gold(III) or of nitric acid (Scheme 1.8). 

Nitration is widely applicable, can be carried out under a variety of conditions, can usually be stopped cleanly after mononitration, is usually effected by the nitronium ion, can take place on a neutral molecule or a cation, and in many cases can be considered as the standard aromatic electrophilic substitution. However, this last point must be treated with caution. Depending on the reaction conditions and reagents, the mechanism of the reaction does vary, and accompanying reactions such as oxidation (due to the oxidative action of nitric acid), acetoxylation (by acetyl nitrate), and migration of nitro groups following ipso attack (80MI1) can occur. Ipso nitration processes have been extensively studied by Fischer and co-workers. 

I2 is a very weak electrophile. It is just reactive enough to attack the para position of aniline. Phenol ethers are attacked by iodine only in the presence of silver(I) salts (—> Agl + I3 ). Benzene and alkyl benzenes react with I2 only when the iodine is activated still more strongly by oxidation with iodic or nitric acid. 

Electrophilic processes which cause C-substitution are not well known. Nitration with nitric and sulfuric acids 2-nitrated 1,4,5-trimethylimidazole 3-oxide <93CHEI27>, but ring cleavage is common with this reagent <92ZOR2582>. Whereas some examples of nucleophilic attack in the 2-position are known, simultaneous deoxygenation is also likely to occur <93CHE127>. 

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