1.2- Enediamines oxidation

Dihydropyrazines are formed by the self-condensation of a-aminocarbonyl compounds and they are relatively stable, although again they are easily oxidized to the corresponding pyrazines. Tetrahydropyrazines are less well documented and structures such as (87) appear to be more stable than the enediamine (88). 

Although no direct evidence was found in the cobalt-N-hydroxyethylethyl-enediamine reaction that an oxygen-cobalt addition complex was formed, it seems reasonable to postulate that such an intermediate is present in the reaction. An oxygen-cobalt complex intermediate appears to afford the most logical method of explaining the evidence that the oxidation of cobalt (II) to cobalt (III) occurs in conjunction with the oxidative cleavage of the carbon-carbon bond of the hydroxyethyl group and the formation of ethylenediamine. 

Mager and Berends190 suggest that A,A -dibenzoyl-o-phenyl-enediamine is obtained as a by-product during the oxidation of 2,3-diphenylquinoxaline with hydrogen peroxide and acetic acid as a consequence of the initial formation of the hydroperoxide 181. 

Benzimidazoles are obtained when thioureas are treated with o-phenyl-enediamine.320,365,366 Also a benzimidazole product 209 is formed when l-(2-aminophenyl)-3-phenyl-2-thiourea (210) is oxidized with mercury(II) chloride,367 or is heated in hydrochloric acid.311 Matsui et al.36B have recently found that 2-aminobenzimidazoles are produced... 

Recently, there is a unique Mb reconstituted with the non-porphyrinoid metal complex. Watanabe and co-workers successfully inserted [Crra(salo-phen)]+ (salophen N, A -bis(salicylidene)-l,2-phenyl-enediamine into apoMb to yield a semisynthetic metalloenzyme (88). They used a H64D/A71G mutant as the apoprotein, because the H64D mutation may allow easy access of a substrate and oxidant and the A71G mutation increases the binding affinity of... 

On the other hand, oxidation of secondary 1,1-enediamines 176 with bromine results in the formation of isothioazole derivatives 179. The yields of the oxidation-cyclization reaction depend strongly on the substituent R2 (equation 71)21,143. It is noteworthy that oxidation of 177 under the same conditions does not furnish isothioazoles but, instead, benzothiazoles 180 are formed (equation 72)21. A similar product, 180, has been obtained in the case of the nitro-substituted enediamines of pyrrolidine143. The different outcomes of these reactions reveal that the reactivity of the secondary amino group of 1,1-... 

Surprisingly, acyclic 1,1-enediamine analogues react with 194 to give products 196 with elimination of HN02. Oxidation of 196 leads to 2,3-diphenylmaleimides (197) (equation 81). The products were identified on the basis of spectral data and by comparison with authentic samples. The mechanism proposed starts with attack of the enamine nitrogen on the carbonyl moiety of 194. 

Enediamines react vigorously with nitrile oxides to give isoxazoles 221 in good yields (equation 91)171. 

In contrast to the cycloaddition of simple 1,1-enediamines, the reaction between conjugated 1,1-enediamines and nitrile oxides proceeds at a slower rate and the yields of products 222 are low (equation 92)172,173. 

Nitrile oxides have also been examined as reagents towards benzoyl-substituted 1,1-enediamines 8178,179. Due to the rapid dimerization of the nitrile oxide, no reaction between 8 and 4-nitrobenzonitrile oxide took place. However, 8 reacts smoothly with... 

A few examples of oxidation reactions of 1,1-enediamines are known31,181-183. An oxidative coupling reaction of simple 1,1-enediamines with silver ion181 or carbon tetrabromide182 has been reported. Oxidation of dienetetramines 231 leads to the dication-substituted carbocyclic products 232 (equation 96). The most plausible mechanism involves dimerization of two radical cations181. 

Benzoyl-substituted anilino 1,1-enediamines 233 underwent oxidative cyclization with lead tetraacetate (LTA) to give iminoisoxazolines 235 in moderate yields183. In some cases, substituted indoles 236 were also formed. The formation of 235 and 236 has been assumed to arise through the initially formed JV-plumbylated adducts 234 (Scheme 14). 

Alkyl-2-imidazolines 544 are in equilibrium with the enediamine tautomers 545 through which carbon-bound diazenium diolates 546 are formed upon reaction with nitric oxide (Scheme 125) <2005JOC7647>. 

Alkyl-2-imidazoline can exist as the enediamine tautomer, which will react with electrophiles such as nitric oxide <2005JOC7647> (see Section 4.02.6.2.1). 

Intramolecular cyclization is a general reaction in the anodic oxidation of substituted amino alkenes. Thus, the already mentioned A-methyl-A-phenyl-1,2,2-triphe-nylvinylamine leads to a new 3/7-indole by anodic oxidation in the presence of 2,6-lutidine [149,150]. The corresponding enediamine undergoes an electrolytic double cyclization to form an indolooxazolidine [149]. The formation of isoquinolines, benzaze-pines, and tetrahydrocarbazoles may also be obtained by anodically initiated intramolecular cyclization of A-benzyl, A- S-phenethyl, and anilino enaminones [Eq. (30)] [158]. 

Certain metals have a profound influence on the activity of the enzyme. Copper in concentrations as low as those resulting from contamination of glassware and reagents will catalyze nonenzymatic oxidation of p-phenyl-enediamine. For this reason it was recommended that 10 M EDTA (ethylenediaminetetraacetic acid) be incorporated in the reaction mixture (B28). However, higher concentrations of EDTA inhibit the enzyme, and it has been suggested that EDTA may form a complex with copper in ceruloplasmin and thereby inactivate the enzyme (H20, K3). The addition of EDTA to the reaction mixture therefore may not be desirable. We found that by simply avoiding copper contamination, by the use of precautions necessary in copper determinations, the nonenzymatic oxidation of p-phenylenediamine slows to an imperceptibly low rate, and in this situation there is of course no need to add EDTA. 

THF models transfer their C-2 fragment in between 1,4- or 1,5-binucleophilic sites to generate five- or six-membered rings. The acid-catalyzed reactions of 2-aryloxazolidines and oxazinanes with o-aminobenzamide, o-aminothiophenol, and o-phenylenediamine give 2-aryl-4( 1 //)-quinazolinones 69, 2-arylthiazoles, and a mixture of 2-arylbenzimidazole and l-benzyl-2-arylbenzimidazole 68, respectively. Whereas benzothiazole and benzimidazole could be formed by air oxidation of their initially formed dihydro derivatives, l-benzyl-2-phenylbenzimidazole, as formulated below, could arise from initially formed diimine, its cyclization, and subsequent 1,3-hydride shift (88JCR(S)322, 89IJC(B)802). It is the sole product when o-phenyl-enediamine and the model are used in 1 2 stoichiometry. 

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