Pyridine 1-oxides free-radical

Pyridine has been phenylated with the following free-radical sources benzenediazonium chloride with aluminum trichloride the Gomberg reaction " phenylhydrazine and metal oxides A -nitroso-acetanilide dibenzoyl peroxide phenylazotriphenylmethane di-phenyliodonium hydroxide and electrolysis of benzoic acid. ° Although 2-phenylpyridine usually accounts for over 50% of the total phenylated product, each of the three phenyl derivatives can be obtained from the reaction by fractional recrystallization of the... 

This was also accomplished with BaRu(0)2(OH)3. The same type of conversion, with lower yields (20-30%), has been achieved with the Gif system There are several variations. One consists of pyridine-acetic acid, with H2O2 as oxidizing agent and tris(picolinato)iron(III) as catalyst. Other Gif systems use O2 as oxidizing agent and zinc as a reductant. The selectivity of the Gif systems toward alkyl carbons is CH2 > CH > CH3, which is unusual, and shows that a simple free-radical mechanism (see p. 899) is not involved. ° Another reagent that can oxidize the CH2 of an alkane is methyl(trifluoromethyl)dioxirane, but this produces CH—OH more often than C=0 (see 14-4). ... 

The autoxidation mechanism by which 9,10-dihydroanthra-cene is converted to anthraquinone and anthracene in a basic medium was studied. Pyridine was the solvent, and benzyl-trimethylammonium hydroxide was the catalyst. The effects of temperature, base concentration, solvent system, and oxygen concentration were determined. A carbanion-initi-ated free-radical chain mechanism that involves a singleelectron transfer from the carbanion to oxygen is outlined. An intramolecular hydrogen abstraction step is proposed that appears to be more consistent with experimental observations than previously reported mechanisms that had postulated anthrone as an intermediate in the oxidation. Oxidations of several other compounds that are structurally related to 9,10-dihydroanthracene are also reported. 

The reaction of alkylene oxides or epoxides with sulfur dioxide to give cyclic sulfites is effected by carrying out the reaction at about 150°C for 4 hr at 2000 atm of S02 [28]. Pyridine is used in small amounts as a polymerization inhibitor. In addition, it has been reported that free radical-producing catalysts give improved yields and allow the reaction to be carried out at lower temperatures [28] (Eq. 19). 

The preferred position for electrophilic substitution in the pyridine ring is the 3 position. Because of the sluggishness of the reactions of pyridine, these are often carried out at elevated temperatures, where a free radical mechanism may be operative. If these reactions are eliminated from consideration, substitution at the 3 position is found to be general for electrophilic reactions of coordinated pyridine, except for the nitration of pyridine-N-oxide (30, 51). The mercuration of pyridine with mercuric acetate proceeds via the coordination complex and gives the anticipated product with substitution in the 3 position (72). The bromina-tion of pyridine-N-oxide in fuming sulfuric acid goes via a complex with sulfur trioxide and gives 3-bromopyridine-N-oxide as the chief product (80). In this case the coordination presumably deactivates the pyridine nucleus in the 2 and... 

In a number of earlier studies the oxidation of NADH or NADPH was assayed under conditions (acid pH, Mn ) in which there was a large component of what appears to be a chain reaction propagated by free radicals Under these conditions it is difficult to be certain how much of the formation of O and of the oxidation of pyridine nucleotides was due to turnover of the enzyme and how much was due to the chain reaction. 

Bipyridyl (20) (63AHC(2)179) is synthesized by oxidative dimerization of pyridine over hot Raney nickel, while 4,4 -bipyridyl (21) (B-79MI10705) is made by free radical coupling of the pyridine radical anion generated by sodium in liquid ammonia, followed by air oxidation (Scheme 6). Quaternization of (21) with methyl chloride gives paraquat while reaction of (20) with 1,2-dibromoethane gives diquat. 

Three facts account for the need of cells for both the flavin and pyridine nucleotide coenzymes (1) Flavins are usually stronger oxidizing agents than is NAD+. This property fits them for a role in the electron transport chains of mitochondria where a sequence of increasingly more powerful oxidants is needed and makes them ideal oxidants in a variety of other dehydrogenations. (2) Flavins can be reduced either by one- or two-electron processes. This enables them to participate in oxidation reactions involving free radicals and in reactions with metal ions. (3) Reduced flavins... 

At least two systems can be cited as catalysts of peroxide oxidation the first are the iron (III) porphyrins (44) and the second are the Gif reagents (45,46), based on iron salt catalysis in a pyridine/acetic acid solvent with peroxide reagents and other oxidants. The author s opinion is that more than systems for stress testing these are tools useful for the synthesis of impurities, especially epoxides. From another point of view, they are often considered as potential biomimetic systems, predicting drug metabolism. Metabolites are sometimes also degradation impurities, but this is not a general rule, because enzymes and free radicals have different reactivity an example is the metabolic synthesis of arene oxides that never can be obtained by radical oxidation. 

The free-radical arylation of pyridine N-oxides has not been studied systematically, alkylation not at all. When pyridine A-oxide was treated with benzene- and p-chlorobenzenediazonium salts only the 2-arylpyridine jV-oxides were isolated.393 No mention was made of the formation of the 3- and 4-aryl derivatives expected to be produced as well. The phenylation of pyridine N-oxide (diazoaminobenzene at 131° or 181° was found to be the most convenient source of phenyl radicals) was reinvestigated,394 and the reactivities of the nuclear positions found to be in the order 2 > 4 > 3, which is also that predicted6 on the basis of atom localization energy calculations. 2-Phenyl-pyridine N-oxide formed 71-81% of the total phenylation products, whereas the 3-isomer comprised only 5.6-9.6% of that total. The phenylpyridines were found among the by-products of the reaction. 

Hydrogen peroxide is also the oxidant in the halogenations of alkanes under Gif conditions. In these systems, developed by Barton and his coworkers312, alkanes are selectively transformed into alkyl chlorides or bromides by polyhaloalkanes and H202 in the presence of FeCypicolinic acid catalyst in pyridine/acetic acid solvent313-315. It has clearly been established that the reaction mechanism does not involve a free-radical intermediate. 

By phenyl substitution on the pyridine moiety or by using isoquinolinium-N-oxides the absorption of the pyridinium salts can be extended to longer wavelengths [47]. Table 3 summarizes the absorption characteristics of the pyridinium salts which are used as cationic photoinitiators. In Fig. 2 the absorption maxima are compared to the emission lines of mercury. The photosensitivity of these pyridinium salts lies in the short wavelength region of the UV spectrum. Thus, pyridinium salts have to be used with sensitizers or free radical sources in order to extend their sensitivity into the region between 350-400 nm. 

Chromyl chloride, Cr202Cl2, a dark-red liquid (mp -96.5 °C, bp 117 °C, d 1.911), is prepared from chromium trioxide or sodium dichromate, hydrochloric acid, and sulfuric acid [665]. The reagent is used in solutions in carbon disulfide, dichloromethane, acetone, tert-butyl alcohol, and pyridine. Oxidations with chromyl chloride are often complicated by side reactions and do not always give satisfactory yields. The mechanism of the oxidation with chromyl chloride, the Etard reaction, is probably of free-radical nature [666]. Complexes of chromyl chloride with the compounds to be oxidized have been isolated [666, 667, 668]. 

Research on the biochemical effects of 03 has been extensive. Among the many mechanistic postulations that have been advanced concerning the toxicity of 03, the following are noted (1) reactions with proteins and amino acids (2) reactions with lipids (3) formation of free radicals (4) oxidation of sulfhydryl compounds and pyridine nucleotides (5) influence on various enzymes and (6) production of more or less nonspecific stress, with the release of histamine. 

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