Hydroxylamine reaction

Fig. 8.17. Mechanism of bioactivation of self-immolative carbamate prodrugs of cytotoxic amines. A bacterial nitroreductase coupled to a tumor-directed antibody reduces the prodrug to a hydroxylamine (Reaction a), which breaks down spontaneously to liberate the antitumor...

Unlike the hydroquinone and hydroxylamine reactions, the p-phenylenediamine reaction shows a strong positive salt effect. The pH depend-... 

The reduction of silver chloride by hydrazine shows some points of similarity to the action of hydroxylamine, but also some important points of difference (James, 34). An induction period was obtained with the unnucleated precipitates which, under some conditions, was relatively large. However, exposure of the precipitate to actinic light had only a small effect upon the induction period and upon the subsequent course of the reaction. Previous nucleation of the precipitate by the action of hydroxylamine decreased the induction period without eliminating it, and produced little or no effect upon the subsequent course of the reaction. Addition of the dye, 3,3 -diethyl-9-methylthiacarbocyanine chloride, produced no effect until the surface of the precipitate was more than half covered. Further increase in the amount of dye added produced an irregular decrease in the reaction rate. Gelatin decreased the reaction rate, but to a smaller extent than in the hydroxylamine reaction, and a minimum rate was not attained. As the gelatin concentration increased, more and more reduced silver appeared in colloidal form in the solution. 

A large part of the reduction of silver chloride by hydrazine evidently takes place by a different mechanism from that of the reduction by hydroxylamine. The effect of gelatin and dye on the process, together with the appearance of colloidal silver in the solution when gelatin is present to stabilize it, shows that the reaction involves dissolved silver chloride to a greater degree than the hydroxylamine reaction. Indeed, if the reaction rate is plotted against a silver ion concentration calculated on the assumption that a saturated solution of silver chloride is maintained, the same relation is obtained as is found for the reduction of silver ions from a solution of the sulfite ion complex. 

The essential difference between the hydroxylamine reaction and the hydrazine reaction appears to be that silver nuclei are formed in the solution much more readily by hydrazine than by hydroxylamine. At sufficiently low pH and in the absence of copper, hydroxylamine does not readily form nuclei in the solution, and the catalytic reduction of the silver chloride occurs essentially at a solid interface with the silver nuclei. Hydrazine, on the other hand, readily forms nuclei in the solution and an important fraction of the total reaction involves the catalytic reduction of dissolved silver chloride. This would account for the well-known photographic properties of the two agents. Hydroxylamine is a cleanworking developer which, under proper conditions, yields little fog. Hydrazine shows much less selectivity and, although it develops an image, it also yields a relatively high fog density. 

Cupric sulfate exerts an effect on the silver chloride-hydroxylamine reaction similar in kind to that which it exerts on the hydrazine reaction, but in a smaller degree. If sufficient cupric sulfate is added to the hydroxylamine solution, the character of the reduction of silver chloride shifts towards that shown by the hydrazine reaction, e.g., the effect of gelatin becomes less pronounced, a minimum rate at a small gelatin addition is not obtained, and significant amounts of colloidal silver appear in the solution. 

A reactive intermediate may be responsible for the copper catalysis of the hydroxylamine reaction. The intermediate formed in the silver-catalyzed reaction, if it has any real existence, is not further oxidized but breaks down into nitrogen and water. Oxidation of hydroxylamine by cupric ion, on the other hand, yields predominately nitrous oxide. The intermediate formed by the removal of a single electron from the hydroxylamine in this reaction must be further oxidized to yield the final product. Such an intermediate may react readily with silver ions in solution. 

Bonner, F. T., Dzelzkalns, L. S., and Bonucci, J. A. (1978). Properties of nitroxyl as intermediate in the nitric oxide-hydroxylamine reaction and in trioxodinitrate decomposition. Inorg. Chem. 17, 2487-2494. 

The hydroxylamine reaction was used to estimate ketone and aldehyde groups. The method used was similar to one described by Kaverzneva and Salova (6). A 25-ml. solution of 5% aqueous hydroxylamine hydrochloride (previously adjusted to a pH 7.5-8 with sodium hydroxide) was added to 1.5 grams of sample and allowed to react for 18-24 hours at room temperature. The mixture was filtered, washed with water, and dried. The residue was analyzed for nitrogen, and the amount of aldehyde and ketone structure was calculated from the nitrogen increase. 

Results obtained from the hydroxylamine reaction of carbonyl groups... 

Under thermal conditions, hydroxylamine ethers can reversibly decompose (Reaction 15). The radicals formed disproportionate to eliminate olefins and yield hydroxylamine (Reaction 16). In the presence of sufficiently effective acceptors of alkyl radicals (e.g., oxygen), the reaction rate of peroxy radical formation is much higher than that of hydroxylamine formation. Thus, in the process of polymer photooxidation, nitroxyl radicals regenerate and can break multiple oxidative chains. 

Secondary and primary amines also undergo N-oxygenation and the first isolable metabolites are hydroxylamines (reactions 3-A and 4-A, respectively). Again, reversibility is documented (reactions 3-B and 4-B). These compounds can be aliphatic or aromatic amines, and the same metabolic pathway occurs in secondary and primary amides (i.e., R = acyl), whereas tertiary amides seem to be resistant to N-oxygenation. The oxidation of secondary amines and amides usually stops at the hydroxylamine/hydroxylamide level, but formation of short-lived nitroxides (not shown) has been reported. 

Figure 7. Nitrite formation from hydroxylamine. Reaction mixture contained in 3 mL 50 mM phosphate buffer pH 7.8 1 fjjnol of NH OH chloroplasts with 75 /xg of chlorophyll and where indicated 6.6 /aM paraquat 50 units SOD. Illuminated at 275 Wm at 22°C. Key control, plus paraquat. A plus SOD, and plus paraquat and SOD, A (72).

Nitroxyl radicals may also react with polymer radical to form hydroxylamine (Reaction 1.98), and the latter can react with peroxy radicals and hydroperoxides according to Reaction 1.99 and Reaction 1.100 ... 

Sulfamic acid, NH2SO3H, is an ammonoaquosulfuric acid in which one of the hydroxyl groups of sulfuric acid has been replaced by the isosteric amido group. It is prepared commercially by the interaction of fuming sulfuric acid and urea. This method is not readily adaptable to laboratory preparation on a small scale. Consequently, the sulfur dioxide-hydroxylamine reaction is recom-mended.H Sulfamic acid may also be obtained by the action of sulfur dioxide upon certain compounds which yield hydroxylamine such as acetoxime. The recommended procedures are modifications of older processes and involve the use of sulfur dioxide under pressure upon aqueous solutions of hydroxylammonium salts and compounds yielding hydroxylamine. 

When phenyl glyoxal is used as substrate, the formation of a thiol ester can be readily demonstrated with the hydroxylamine reaction. The spectrophotometric test is not suitable in this particular case because of absorption exhibited by phenyl glyoxal itself. In fact, on addition of GSH and glyoxalase I a decrement in absorption can be observed at 240 m/u, instead of the expected increment. 

Wolfe, S. K., et aL "Kinetic Studies of the Pentacyanord-trosoylferrate(2-)-Azide and -Hydroxylamine Reactions." Inorganic Chemistry, 131974,2567-2572. 

Supply the structures of intermediates after each step in the conversion of 89 —> 90. Provide a model that explains the stereochemical course of the hydroxylamination reaction. (Histrionicotoxin-10)... 

The oxidation of titanium(m) chloride by chlorinated alkyl cyanides has been shown to result in the formation of Ti -chloroalkyl cyanide species, the mechanism suggested involving the transfer of a chlorine atom from the co-ordinated alkyl cyanide to the metal followed by loss of a CCI2CN group. A comparative spectro-electrochemical, stopped-flow kinetic, and polaro-graphic study has been made on the Ti i-hydroxylamine reaction. rate has been shown to be dependent on pH, and in the presence of 0.2M-oxalic acid (H2OX) the proposed reaction scheme may be expressed as... 

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