Hydroxylamine acidity/basicity

Succinic anhydride also may react with protein phenolate side chains of tyrosine residues and the —OH group of aliphatic hydroxy amino acids (Figure 1.82). The phenolate ester derivatives are unstable above pH 5.0, whereas the serine and threonine esters are more stable but may be cleaved by treatment with hydroxylamine at basic pH (Gounaris and Perlman, 1967). 

Synthesis. Deoxybenzoin is converted to the corresponding oxime by treatment with hydroxylamine under basic conditions with sodium acetate in aqueous ethanol or in toluene in the presence of potassium hydroxide in absolute ethanol. Treatment of the oxime under nitrogen with two equivalents of butyllithium in tetrahydrofurane is followed by cyclization in ethyl acetate or acetic anhydride to the isoxazoline derivative. Finally, treatment of the isoxazoline with cold chlorosulfonic acid followed by reaction of the intermediate with aqueous ammonia affords the desired product. (Talley, 2000a Sorbera, 2001b). 

The partial reduction of diones has been accomplished by initial reaction with 0-(2-dimethylaminoethyl)hydroxylamine, acid extraction of the basic monooxime, sodium borohydride reduction, and hydrolysis to regenerate the carbonyl function. "... 

Reacting hydroxylamine with the corresponding trichloro derivative (462) under acidic conditions gave an oxazinone (463) while under basic conditions the 2-isoxazoline (464) was produced (80ZC19). 

Forsyth et al. found that gelsemicine contains three active hydrogen atoms (Zerewitinov determination), yields a non-basic, monobenzoyl derivative, m.p. 232°, and behaves as a secondary base giving JV-methyl-gelsemicine hydriodide, m.p. 227°, on treatment with methyl iodide. It does not react with either hydroxylamine or 2 4-dinitrophenylhydrazine. On hydrogenation in dry acetic acid in presence of Adams s platinic oxide catalyst it absorbs three molecules of hydrogen. 

The hydroxy group of furazan 263 reacted with cyanogen bromide in glyme in the presence of Li2C03 to give cyanate 264 in 70-85% yield (97MI8). Upon treatment with Mc4NN3 and subsequently with a basic solution of hydroxylamine-0-sulfonic acid, /V-aminotetrazole 265 was obtained in 35% yield (Scheme 171). 

Other nitrogen compounds, among them hydroxylamine, hydrazines, and amides (15-9), also add to alkenes. Even with amines, basic catalysts are sometimes used, so that RNH or R2N is the actual nucleophile. Tertiary amines (except those that are too bulky) add to Michael-type substrates in a reaction that is catalyzed by acids like HCl or HNO3 to give the corresponding quaternary ammonium salts. " ... 

If the formation and breakdown steps of a mechanism involving a tetrahedral intermediate respond differently to changes in pH or catalyst concentration, then one can find evidence from plots of rate versus pH or rate versus catalyst concentration for a change in rate determining step and thus for a multistep mechanism. An example would be the maximum seen in the pH rate profile for the formation of an imine from a weakly basic amine (such as hydroxylamine). On the alkaline side of the maximum, the rate determining step is the acid-catalyzed dehydration of the preformed carbinolamine on the acid side of the maximum, the rate determining step is the uncatalyzed addition of the amine to form the carbinolamine. The rate decreases on the acid side of the maximum because more and more of the amine is protonated and unable to react. 

Reactions of 2,3-dioxo-l,2,3,5,6,7-hexahydropyrido[l,2,3-carboxylic acids and the homologous acetic and propionic acids, prepared by basic hydrolysis of the corresponding ester, with amines, 28% NH4OH, and hydroxylamine derivatives in the presence of l-ethyl-3-[3-(dimethylamino)propyl]carbodiimide and hydroxybenztria-zole <1995BML1527>, 1995BML1533>, and in the presence of NEt3 and A, A -bis(2-oxo-3-oxazolidinyl)phosphinic... 

Oximes generally demonstrate good stability in the solid state when stored at low temperature. Simple oximes show reasonable stability in neutral aqueous solution but hydrolyze to hydroxylamine and the parent ketone under acidic or basic catalysis [2], As noted, nitro-containing oximes, such as FK409 (9), spontaneously decompose... 

Esters ofN,N-dialkylhydroxylamines ((acyloxy)amines) appear to be possible candidates for prodrugs of carboxylic acids, but more studies must be published before any firm conclusion can be drawn. First, there are indications of low acute toxicity for N,N-(1 al ky I hydroxy Iambics [87], Whether the same applies (acutely and chronically) to the pro-moieties after their release from the prodrugs is not known. A second argument is the low basicity of hydroxylamines (the pKa of Ar,AT-dimethylhydroxylamine is 5.2), and the expected lower basicity of O-acylatcd hydroxylamines. As a result, esters of hydroxylamines will be in the unprotonated, more lipophilic form at physiological pH and should be absorbed more readily than the corresponding carboxylic acid [88]. 

Oxidative deamination basically resembles the dealkylation of tertiary amines, beginning with the formation of a hydroxylamine that then decomposes into ammonia and the corresponding aldehyde. The latter is partly reduced to an alcohol and partly oxidized to a carboxylic acid. 

Types of compounds are arranged according to the following system hydrocarbons and basic heterocycles hydroxy compounds and their ethers mercapto compounds, sulfides, disulfides, sulfoxides and sulfones, sulfenic, sulfinic and sulfonic acids and their derivatives amines, hydroxylamines, hydrazines, hydrazo and azo compounds carbonyl compounds and their functional derivatives carboxylic acids and their functional derivatives and organometallics. In each chapter, halogen, nitroso, nitro, diazo and azido compounds follow the parent compounds as their substitution derivatives. More detail is indicated in the table of contents. In polyfunctional derivatives reduction of a particular function is mentioned in the place of the highest functionality. Reduction of acrylic acid, for example, is described in the chapter on acids rather than functionalized ethylene, and reduction of ethyl acetoacetate is discussed in the chapter on esters rather than in the chapter on ketones. 

Hydroxylamines from reduction of nitrocompounds are trapped by reaction with any adjacent carbonyl function under slightly basic conditions. This reaction forms a nitrone, e.g. 1, which can be reduced in acid solution to a pyrrolidine [20]. 

When a molecule contains several potential acidic and/or basic sites, as do those treated in this chapter, the relative /s,mm can help to rank them and also to clarify possible ambiguities. For example, hydroxylamine, H2N—OH, has a reported pK of 5.94 . Does this correspond to the loss of the hydroxyl proton, or an amine proton Or is it telling us that the nitrogen, or the oxygen, has pA"b = 14.00 — 5.94 = 8.06 ... 

TABLE 6. Values of /s.min relevant to the acidities or basicities of hydroxylamine (5), dimethyl-hydroxylamine (6), acetoxime (7) and acetohydroxamic acid (8). The Is min were computed at the HF/6-31GV/B3LYP/6-31G level and are in eV"... 

Conversion of hydroxamic acids into hydroxylamines is usually performed by hydrolysis or alcoholysis under acidic"" or basic catalysis , although other methods like reaction with trimethylsilyl iodide have also been sparingly used. 

The similarity of the results obtained with phenyl azide and N-phenyl-hydroxylamine in benzene/TFA indicates that both reactions proceed by similar mechanisms, but N-phenylhydroxylamine in benzene/TFSA produces a higher yield of the C-substitution products 27 and 28 As previously suggested (Scheme 5), N-phenylhydroxylamine can be doubly protonated to yield the dication 11 in strong acids, but the more weakly basic phenyl azide is less likely to be doubly protonated. The differences observed between the behavior of N-phenylhydroxylamine and phenyl azide in TFSA may be due to the inability of phenyl azide to directly generate 11. 

Another widely used approach is the cyclization of oximes either under acidic, as in the conversion (147 ->148) (71MI22700), or basic conditions (149- 150) (78JOC2020). Cyclopropyl ketones (151) also react with hydroxylamine hydrochloride to give dihydro-1,2-oxazines (153), probably via the protonated oxime (152). If this is so then this reaction represents a rare example of a 6-endo-tet ring closure <80AG(E)199). 

E. Divers prepared the basic salt cupric hydroxy hyponitrite, Cu2(0H)2N202, according to A. Thum. This salt was also made by S. S. Kolotoff, A. Thum, and A. Kirsehner. It is obtained by adding sodium hyponitrite to a soln. of a cupric salt. The acid liquor so obtained deposits more salt when neutralized. A small quantity of this salt is precipitated when an excess of cupric sulphate is added to a soln. of hydroxylamine sulphate, and then a little ammonia. The sea-green salt is very stable it gives water, a mixture of cupric and cuprous oxides, and nitric and nitrous oxides when heated. The salt can be boiled with water without losing its colour, but it is decomposed by a soln. of sodium hydroxide. It is soluble in dil, acids and aq. ammonia. E, Divers tried unsuccessfully to make cuprous... 

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