1.1- Enediamines reduction

The most widely applied precursors for the synthesis of monocyclic NHPs are a-diimines which can be converted to the target heterocycles either in a two-step reaction sequence involving two-electron reduction of the diimine to an enediamide, enediamine, or a-aminoamine and subsequent condensation with PC13 [18-20] or a dichlorophosphine RPC12 [21], or via direct base-promoted reaction with PC13 [20, 22], The latter reaction involves addition of a P-Cl bond to each imine moiety followed by base-promoted elimination of hydrogen chloride leading to 2,4-dichloro-... 

The two-electron reduction of a-diimines to prepare the required starting materials for a subsequent condensation is usually achieved by reaction with lithium but other alkaline (Na) or alkaline earth (Mg) metals should be useful as well. The synthesis of the heterocycles 10 is either accomplished by direct metathesis of the formed metal enediamide with PC132 [19] or, alternatively, by quenching the diamide with a suitable acid to produce an enediamine or a-aminoimine, respectively, and subsequent base-induced condensation with PC13 or RPC12 [18, 20] (Scheme 3). 1,3-l )i-/e/t-butyl-2-chloro-1,3,2-diazaphospholene was also prepared from the reaction... 

Chloropyramine Chloropyramine, iV-(4-chlorobenzyl)-iV, iV -dimethyl-iV-2-pyridylethyl-enediamine (16.1.9), is synthesized in a somewhat different manner, which is by reacting 2-brompyridine with iV-(4-chlorobenzyl)-iV, Af -dimethylethylenediamine (16.1.8). iV-(4-Chlorobenzyl)-iV, iV -dimethylethylenediamine (16.1.8), in turn, is synthesized by condensation of 4-chlorobenzaldehyde c iV,iV-dimethylethylenediamine with subsequent reduction of the imine group [13-19]. 

Bridged 1,5-benzodiazepines (204), prepared by condensation of o-phenyl-enediamine with 4,6-dimethylbicyclo[3.3.1]nona-3,6-diene-2,8-dione, give barbaralanes (205) on electrochemical reduction in acetonitrile in the presence of acetic anhydride338 [Eq. (119)]. The reaction is akin to the reduction of acetylacetone in which cyclopropane derivatives have been formed.339-340... 

Recently, Baum and coworkers154 reported the nitration of 1,1-diamino-2,2-dini-troethylene. On treatment with nitric acid and trifluoroacetic anhydride in methylene chloride at 0 °C, 1,1-enediamines 42 are converted to 3-nitro-2-(trinitromethyl)-l,3-diazacyclic compounds 192 in good yields (equation 79). Compounds 192 have also been prepared from the nitration of 7, although the yields are lower (16-22%). Denitration of 192 to 193 includes a reductive denitration of 192 with potassium iodide and acidification of initially formed salts of 193. Nitration of 193 regenerates 192 (equation 79). 

The electrochemical reduction of 2,3-disubstituted 5,6-dihydro-pyrazines (165a) yields the 1,4,5,6-tetrahydropyrazines (166)169 the diimine-enediamine system is thus analogous to the dione-enediol system. It is of interest that the 5,6-dihydropyrazines are somewhat more easily reduced than the pyrazines. 

Reductive coupling of amides. Tertiary amides are converted to enediamines. Acid hydrolysis of the products furnishes a-aminoketones. 

A related synthesis of fused pyrazines employs 3,4-dlamlnothlophenes (ingeniously prepared from pyridine as depicted below) as latent enediamines condensation with 1,2-dicarbonyl compounds gives thieno(3,4-b)pyrazines which would appear to potential intermediates to novel pyrazines by reductive desulfurization. 

Catalytic reduction of nitro-substituted 1,1-enediamines 174 gives the aminomethyl amidines 238 in good yields. Apparently, reduction of the nitro group gives the triamine intermediates 237 which undergo a rapid prototropic shift to afford 238 (equation 97) . Attempts to reduce the benzoyl-substituted 1,1-enediamines 8 were unsuccessful . These results are not unexpected, since the double-bond character in 8 is reduced due to the strong conjugation effect. 

The mechanism of this dehydrogenation was investigated by studying the distribution of radioactivity using phenyP C-hydrazine, whereby it was shown that no intramolecular oxido-reduction takes place, but rather, that the enediamine form causes hydrogenation of the free phenyl-hydrazine present in the reaction mixture, to yield aniline and ammonia. This mechanism was criticized by Weygand when this work was presented, and the problem of intermolecular or intramolecular oxido-reduction still awaits settlement. 

When the compound to be treated contains more than one nitro group, the products of reduction depend upon the agents used. Thus, m-phenyl-enediamine is obtained by the iron and acid reduction of m-dinitrobenzene, while the alkaline sulfide reduction yields m-nitroaniline ... 

Figure 12 illustrates benefits obtained by interpolation of an a.c. cyclic voltammogram obtained using the FT-FAM procedure. The system involves the one-electron reduction of the tetramethylphenyl-enediamine cation (TMPD ) at the platinum-0.10 M tetrabutylammonium perchlorate, acetonitrile interface. Under these conditions the electrode reaction may be characterized as quasireversible on the d.c. time scale. Such systems are predicted to exhibit unequal forward and reverse scan admittance voltammograms which include a cross-over point at a particular d.c. potential.43 The d.c. potential of the crossover point can be used to measure an important... 

Reduction of dinitrotoluenes is carried out industrially with Raney-nickel or palla-dium/carbon catalysts, under a hydrogen pressure of 70 bar and at a temperature of up to 150 °C, in a cascade or loop reactor. The concentration of dinitrotoluene in the reaction mixture is kept very low to achieve yields of over 99%. The reaction mixture is divided into a recycle stream and a residue, from which the catalyst is separated in a filter or cyclone. Distillation of the reaction product then yields the components methanol, water, diamines and a residue. Distillation of the water-free amines is carried out under vacuum (approx. 50 mbar), with 2,3- and 3,4-tolu-enediamine being separated in a fronts column. A tar-like residue is removed as a bottom product in the main column, while a mixture containing 2,4- and 2,6-tolu-enediamine is collected as an overhead fraction. 

Of the derivatives of p-phenylenediamine, the most effective are the N, N -di-alkyl derivatives, in which the alltyl possesses a branched hydrocarbon chain on the carbon closest to the nitrogen atom [235]. They are usually produced by reductive allq lation of p-nitroaniline, p-phenyl-enediamine, p-nitrodiphenylamine, p-nitrosodiphenylamine, or p-amino-diphenylamine with aldehydes and ketones [236-252] with hydrogen at a temperature of 100-250°C and a pressure from 5 to 200 atm in the presence of catalysts. Copper-chromium catalysts (mixtures of oxides of the metals chromium, copper, barium, etc.) [241, 242, 245-247, 249, 250], iodine in the presence of HCl, HBr, or HI [253, 254], Pt/C [245, 252], and Raney nickel [244] are most often used as the catalysts. 

General.—Aliphatic seleno-esters RCSeOEt condense with o-phenyl-enediamine, o-aminophenol, or o-aminothiophenol to yield the benzazoles (510 X = NH, O, or S, respectively). Cyclic voltammetry of the salts (511 X, Y = O, S, or Se R = SEt or SeEt) results in electrochemical reduction to dimers. The rates of base-catalysed hydrogen-deuterium exchange in the 2-position of compounds (510 X = 0, S, or Se R = H) have been determined. Successive treatment of 1,8-dibromonaphthalene with butyl-lithium, sulphur, butyl-lithium, and selenium gives naphtho[l,8-Cif]-l,2- selenathiole (512 X = S, Y = Se) the tellurathiole (512 X = S, Y = Te) and the telluraselenole (512 X = Se, Y = Te) were prepared similarly. ... 

The rate of reduction of cytochrome a was examined by addition of various chemical reductants such as p-phenylenediamine, hydro-quinone, and ascorbic acid. These were then tested as substrates for the cytochrome oxidase, the activity of which was measured manometrically. Onlyp-phenylenediamine reduced cytochrome a, while the other reagents tested, except sodium dithionite, had weak reductive activity. In Fig. 11, it is shown that cytochrome a is oxygenated under aerobic conditions and is reduced under anaerobic conditions by addition of 10 Af/>-phenyl-enediamine and the trace of borohydride, used to decrease the concentration of oxygen in the solution in the cuvette. When a trace of oxidized cytochrome c is added to either system, both forms of cytochrome a are instantaneusly oxidized. As shown in Table IX (see Section III.C), the cytochrome a acquires an oxidase activity in cooperation with cytochrome c when the oxygen consumption is measured manometrically in the presence and absence of cytochrome c. 

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