Nucleophilic attacks nitric oxide

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. 

Goheen and Bennett9 showed that regular nitric acid could be used, in about two molar excess, for the oxidation of dimethyl sulphoxide to dimethyl sulphone in 86% yield. The reaction temperature was 120-150°C with a reaction time of about 4 hours. The mechanism for this reaction was postulated to involve initially a protonated sulphoxide species (which has been shown to be present in other strongly acidic systems101 ) followed by nucleophilic attack by nitrate, and the loss of nitrogen dioxide as shown in equations (4) and (5). 

At low acid concentrations, nitric oxide tends to form. This evidently may attack nitrosophenol to form diazonium compounds directly. The diazonium salts, in turn, may couple with unreacted phenol to give colored products. Nitrous acid may also produce nitrophenols from phenols. The mechanism of this reaction may involve oxidation of initially formed nitrosophenols, homolytic attack by nitrogen dioxide, or nucleophilic attack by nitrite ions [1]. 

Nucleophilic attack can occur at the nitrogen atom in NO+ complexes where there is strong (7-donation and weak Tt-acceptance by the ligand. In such species, which are often cationic, electron density is drawn from the nitric oxide group. This results in an increased N—O bond order and is thus reflected in the observation of a high NO stretching frequency. Consequently IR data can be used loosely as a criterion for susceptibility to attack by nucleophiles. 

Chromium hexacarbonyl is extremely photolabile (equation 6) therefore photochemical substitution is an efficient means of preparing derivatives. Oxidation of the Cr center requires nitric or sulfuric acid, or chlorine. Alternatively, some hgands induce complete carbonyl dissociation with concomitant oxidation, for example, acetylacetonate. Chemical reduction with alkali or alkaline-earth metals or electrochemical reduction proceeds in two-electron steps with loss of two CO molecules to first give [Cr2(CO)io]" and then [Cr(CO)s]. Nucleophilic attack at CO generates a number of stable (Nu = R) and unstable (Nu = N3, OH, H, NEt2) products. The stable [(OC)5CrCOR] ion is a carbene precursor. 

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>. 

The second direct reaction pathway, one-electron reduction of a target by nitric oxide, could occur only if the target was itself a strong oxidant, since nitric oxide does not readily give up its unpaired electron. Oxidation of nitric oxide would result in the formation of NO, which would rapidly nitrosate nucleophiles such as amines, sulfhydryls, or aromatics. In fact, the best one-electron oxidants would be radicals such as -NOi or hydroxyl radical or even ONOO itself. In such cases the net effect would be nitric oxide addition reactions (nitrosations), regardless of whether the mechanism is considered to be transfer of an electron from nitric oxide followed by attack of NO or simple radical-radical combination. Thus, under most conditions, one-electron reduction of a target by nitric oxide becomes a simple addition reaction. 

The N-3 nitrosation of 8 (X = O, R = Et) with nitric oxide regioselec-tively furnished N-3 nitrosamides 137 by nucleophilic attack of N-3 of 8 on N2O3 (formed in situ from oxidation of NO by O2) in the presence of aprotic and polar solvents (Scheme 51) (08TL1220). 

The next stage of the reaction can be viewed as a further oxidation to yield a diketone. This stage is initiated by nucleophilic attack on a nitronium ion (NO ) derived from either the nitric or nitrous add. The nudeophile is the enol tautomer of the ketone, and the reaction forms an a-nitrosoketone, w hich is in tautomeric equilibrium with a mono-oxime. This spedes rapidly hydrolyzes under acidic conditions to yield an a-diketone intermediate. This sequence is shown here ... 

Benzyl ethers may be converted into their corresponding benzaldehyde derivatives by oxidation with nitric oxide (NO) in the presence of catalytic (V-hydroxyphthaUmide (NHPl). NO reacts with the catalyst to give phthalimide N-oxyl (PINO), which abstracts the benzylic hydrogen atom from the substrate to generate a radical, which reacts in turn with NO to give a carbocation. Nucleophilic attack of water to the cationic species gives the aldehyde via a hemiacetal intermediate. ... 

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). 

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