Nitrogen compounds, autoxidation

Nitrogen Compound Autoxidation. CycHc processes based on the oxidation of hydrazobenzene and dihydrophenazine to give hydrogen peroxide and the corresponding azobenzene—phenazine were developed in the United States and Germany during World War II. However, these processes could not compete economically with the anthrahydroquinone autoxidation process. 

The reactive species that initiate free-radical oxidation are present in trace amounts. Extensive studies (11) of the autoxidation mechanism have clearly established that the most reactive materials are thiols and disulfides, heterocyclic nitrogen compounds, diolefins, furans, and certain aromatic-olefin compounds. Because free-radical formation is accelerated by metal ions of copper, cobalt, and even iron (12), the presence of metals further complicates the control of oxidation. It is difficult to avoid some metals, particularly iron, in fuel systems. 

It is well known that many classes of nitrogen compounds, including imines, enamines and hydrazones of the type RR C=X-NHR (X = CR or N), 9-aminoanthracenes and 2,3-disubstituted indoles, autoxidize spontaneously at room temperature to give hydroperoxides via peroxyl radicals [6c, 8]. An early but pertinent example is the 100-g scale autoxidation of 2-methyl-3-phenyl-3,4,5,6-tetrahydropyridine in cyclohexane (Cy) to provide the corresponding hydroperoxide in excellent yield (Scheme 28) [59]. 

A sample of the monohydroperoxide, previously reported by Bickel and Kooyman (2), was obtained by autoxidation of 9,10-dihydroanthra-cene in benzene under ultraviolet irradiation. When this compound was treated under nitrogen with benzyltrimethylammonium hydroxide, it decomposed to give a mixture of anthracene and anthrone. (Under acidic conditions, it decomposed entirely to anthracene.) A fresh sample of the hydroperoxide was then oxidized. The physical appearance of the reaction mixture was similar to that in the oxidation of anthrone. The product was analyzed, and the conversion to anthraquinone was only 59%. Again, other oxidation products or anthrone may have contributed to the anthraquinone estimate. 

C-Aminoindoles autoxidize extremely rapidly. Consequently, comparatively few chemical reactions have been examined. The 2-amino derivative exists in the 3H-indole tautomeric form (473) and is protonated and alkylated on the annular nitrogen atom (72HC(25-2)179). The 1-methyl derivative (474) exits predominantly as such and not as the alternative 2-imino-3//-indole tautomer and is protonated at the 3-position to give a cation having the same electronic structure as that of the protonated (473). Acylation of (473) yields l-acetyl-2-acetylaminoindole, via the initial acylation of the annular nitrogen atom. Confirmation of this route has been established by the observation that 2-acetylaminoindole, obtained by hydrolysis of the diacetylated compound, is acetylated under identical conditions... 

The methylene group adjacent to a ketone may be oxidized by selenium dioxide to give 1,2-dicarbonyl compounds. It is important to carry out base-catalysed condensations of ketones wherever possible under an atmosphere of nitrogen. The reason is that enolate anions are readily autoxidized by the oxygen in air to form hydroperoxides These may then undergo further reaction including decomposition to form diketones. 

It has been found possible to construct the 1,4-benzothiazine ring by direct interaction of bis-(2-aminobenzene) disulfide (96) with carbonyl compounds.139,140 The reaction is most efficient when conducted under a nitrogen atmosphere with a 1 1 ratio of reactants otherwise, the principle products are benzothiazoles. While reduction of the benzothiazine 97 with sodium borohydride gives a stable dihydro derivative, the unsaturated benzothiazines themselves were prone to autoxidation, giving rise to benzothiazoles and benzothiazine sulfoxides.141... 

The kinetic instability of isoindoles dominates the chemistry of the simple systems and is principally to be ascribed to autoxidation and self-condensation reactions. The self-condensation reactions appear to be more important when both isoindole and isoindolenine tautomers can coexist (Eq. 6) hence, in general, /V-substituted isoindoles are more stable than /V-unsubstituted compounds. Although the autoxidation reactions have been worked out in several cases (Section V,G), the self-condensations are less well understood (but see Section V,F). Isoindole and C-alkylisoindoles become dark when kept at room temperature.6,78 C-Arylisoindoles are somewhat easier to handle, but 2-amino-1,3-diphenylisoindole decomposes rapidly on exposure to light and air.60 Operationally, unless strongly electron-withdrawing substituents are present at carbon, isoindoles must be kept in the freezer under nitrogen. 

Interest in the oxidation of organic compounds containing nitrogen, sulphur, and chlorine has arisen both in its own right and as a result of the fact that these compounds are often used to inhibit the autoxidation of hydrocarbons in solution [1,2]. The present chapter considers both aspects, even though this leads to some small duplication of Chap. 1. Here, however, attention is primarily focused on the reactions and fate of the inhibitor [3—5]. 

The evidence that electron-directing groups also affect the rate and nature of autoxidation of nitrogen-containing compounds has been well reviewed by Hoft and Schultze [51], particularly for the oxidation of amyl phenylhydrazines where it has been possible to relate rates of oxidation with predictions based on the Taft—Hammett relationship [76]. Similar relationships have been established with phenylhydrazones, which have been found to oxidise to produce a hydroperoxide [77]... 

Autoxidation of phenolic compounds may occur during extraction, particularly at alkaline pH values, but can be prevented, or at least limited, by extracting under oxygen-free nitrogen. It is advisable to treat reference compounds in a similar manner. After extraction with water, alkali or EDTA, extracts are acidified, usually to about pH 2.5, to convert the phenolics to the undissociated form. This enables them to be separated by partition into a suitable organic solvent (e.g. diethyl ether, ethyl acetate). In order to minimize the cis-trans isomerisation of the substituted... 

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