Hydroxylamine bases

A. O-Diphenylphosphinylhydi oxylamine. A 5ilO-mL, round-bottomed flask, equipped with a reflux condenser, drying tube, an efficient mechanical stirrer, a dropping funnel and a nitrogen-inlet tube, 1s charged with 300 mL of anhydrous methylene chloride, 16.5 g (0.5 mol) of hydroxylamine base (Note 1), and 1,0 g of dry sodium bicarbonate. While the suspension 1s stirred vigorously at -30°C (bath temperature), a solution of 52.06 g (0.22 mol) of diphenylphosphinyl chloride (Note 2) in 70 mL of anhydrous methylene chloride... 

The 3-(benzhydrylthio)acetic acid methyl ester dissolved in methanol, is added to a solution of hydroxylamine base [prepared by neutralising 0.15 mol (10.4 g) of hydroxylamine hydrochloride with 0.15 mol of sodium methylate]. The whole is left at ordinary temperature (15°-25°C) for 48 h, the sodium chloride is filtered off, the methanol is evaporated, the residue is taken up with aqueous alkali, the solution is filtered over charcoal, the filtrate is acidified with concentrated HCI, and the 3-(benzhydrylthio)acethylhydroxamic acid (recrystallised from benzene) is thus obtained. 

Cl Cl 6 p r= /= MeNHOH OH r= Y nA/om 0 0 [26] Only one example of nucleophilic cleavage with hydrox-ylamine has been described. Recently, many different hydroxylamine-based linkers have been described based on attachement of hydrox-ylamine to trityl-, Wang-, Sasrin- or Rink-resin. [26] [33] [175-177]... 

Electrophilic amination can be achieved using hydroxylamine-based ammonia equivalents. The preferred conditions for this transformation utilize sodium hydride in dioxane. Addition of the anion to 0-(p-nitrobenzoyl)hydroxylamine (NbzONH2) generates theiV-amino-2-oxazolidinone (eq 44). Although the amino compound can be isolated, typically the product is converted to the more stable hydrazone. 

Pale yellow inner complex copper sahcylaldoxime (II) is precipitated. The test for hydroxylamine based on this behavior, like (1), consists therefore in the formation of an inner complex salt from its components. A stock mixture of salicylaldehyde and copper acetate cannot be used as a reagent, because, depending upon the concentration, a green copper salt of salicylaldehyde separates after short or long standing. The reagents must be added separately to the solution in the prescribed order, and concentrations. 

Usually, the transformation into hydroxamic acids is carried out with hydroxylamine sulfate. The hydroxylamine base is liberated by the addition of sodium hydroxide, but particular methods are also proposed. 

For color-critical applications requiring phenol-free stabilization synergistic mixtures of sterically hindered amines (HA (L)S) and a hydroxylamine-based stabilizer, used during melt processing, with or without an organophosphate or organo-phosphonite, can be used to avoid the undesired discoloration typically associated with the oxidation of the phenolic antioxidants into products with quinoid stmctures. ... 

Since hydroxylamine is usually available only in the form of its salts, e.g., the hydrochloride or sulphate, the aqueous solution of these salts is treated with sodium acetate or hydroxide to liberate the base before treatment with the aldehyde or ketone. Most oximes are weakly amphoteric in character, and may dissolve in aqueous sodium hydroxide as the sodium salt, from which they can be liberated by the addition of a weak acid, e.g., acetic acid. 

In current industrial practice gas chromatographic analysis (glc) is used for quahty control. The impurities, mainly a small amount of water (by Kad-Fischer) and some organic trace constituents (by glc), are deterrnined quantitatively, and the balance to 100% is taken as the acetone content. Compliance to specified ranges of individual impurities can also be assured by this analysis. The gas chromatographic method is accurately correlated to any other tests specified for the assay of acetone in the product. Contract specification tests are performed on product to be shipped. Typical wet methods for the deterrnination of acetone are acidimetry (49), titration of the Hberated hydrochloric acid after treating the acetone with hydroxylamine hydrochloride and iodimetry (50), titrating the excess of iodine after treating the acetone with iodine and base (iodoform reaction). 

This reaction, conducted in alkaline solution, also produces carboxyl groups by hydrolysis of the amide (54). Recent work on the reaction of polyacrylamide with hydroxylamine indicates that maximum conversion to the hydroxamate fiinctionahty (—CONHOH) takes place at a pH > 12 (57). Apparendy, this reaction of hydroxylamine at high pH, where it is a free base, is faster than the hydrolysis of the amide by hydroxide ion. Previous studies on the reaction of hydroxylamine with low molecular weight amides indicated that a pH about 6.5 was optimum (55). 

Reactions with Amines and Amides. Hydroxybenzaldehydes undergo the normal reactions with aUphatic and aromatic primary amines to form imines and Schiff bases reaction with hydroxylamine gives an oxime, reaction with hydrazines gives hydrazones, and reactions with semicarbazide give semicarbazones. The reaction of 4-hydroxybenzaldehyde with hydroxylamine hydrochloride is a convenient method for the preparation of 4-cyanophenol (52,53). 

A number of substances, such as the most commonly used sulfur dioxide, can reduce selenous acid solution to an elemental selenium precipitate. This precipitation separates the selenium from most elements and serves as a basis for gravimetry. In a solution containing both selenous and teUurous acids, the selenium may be quantitatively separated from the latter by performing the reduction in a solution which is 8 to 9.5 W with respect to hydrochloric acid. When selenic acid may also be present, the addition of hydroxylamine hydrochloride is recommended along with the sulfur dioxide. A simple method for the separation and deterrnination of selenium(IV) and molybdenum(VI) in mixtures, based on selective precipitation with potassium thiocarbonate, has been developed (69). 

YeUowing of wool can occur during dyeing, depending on pH, temperature and time, and chlorinated wools ate especially sensitive. Bleaching agents that can be added to the dyebath have been developed based on sodium bisulfite and hydroxylamine sulfate (108). Addition of hydrogen peroxide to the dyebath after exhaustion can also be effective. 

In 1888 Claisen (1888CB1149) first recognized a general synthesis of isoxazoles (283) by the condensation-cyclization of 1,3-diketones (280) with hydroxylamine. It is now generally accepted that the monoxime (281) of the 1,3-diketone and the subsequent 5-hydroxy-isoxazoline (282) are the intermediate products of the reaction. The isolation of the monoxime (281) and 5-hydroxyisoxazoline (282), which were both readily converted into the isoxazole (283) by treatment with acid or base, has been reported (62HC(17)l). 

The reaction of a-bromoenone (307) with hydroxylamine hydrochloride in ethanol in the presence of potassium carbonate resulted in the regiospecific formation of 3-alkyl-5-phenylisoxazoles (303). On the other hand, when sodium ethoxide was used as the base under similar conditions, 5-alkyl-3-phenylisoxazoles (308) were obtained exclusively (80CC826, 81H(16)145). 

The reaction of a ,)3-alkynic nitriles (317) with hydroxylamine gave the 5-aminoisoxazoles (318) regiospecifically, whereas in the presence of sodium hydroxide the 3-aminoisoxazoles (319) were obtained exclusively (66CPB1277). Similarly, the course of the cyclization of arylhydrazones (320) was influenced by a change in the base employed (75JOC2604). 

Jurd reported the isolation of a 2//-3-isoxazoline by the reaction of the flavylium salt (488) with hydroxylamine. Gentle heating of the material caused isomerization to the more stable 2-isoxazoline. Treatment with base generated an a,/3-unsaturated oxime which on photolysis regenerated the starting flavylium salt (Scheme 129) (70CI(L)624). 

In a number of cases the intermediate oxime has been isolated in the reaction of hydroxylamine and /3-keto esters. The reaction of ethyl acetoacetate with hydroxylamine generated an oxime which cyclized on base treatment (Scheme 144) (70MI41600). Likewise, treatment of an analogous amide with hydroxylamine generated a ring opened material which cyclized on treatment with HCl (Scheme 144) (67T831). The presence of a minor contaminant in the standard reaction of ethyl acetoacetate with hydroxylamine was discovered and identified as an isomeric isoxazolin-3-one. The mechanism of product formation has been discussed (70BSF2685). 

Ethyl acetoacetate and hydroxylamine with a large excess of alkali produced (516) which on heating generated 4-methylene-2-isoxazoline (517), while limited base generated the dimer (518) (80JHC763). 

The treatment of 2-hydroxyacetophenone with hydroxylamine-O-sulfonic acid in dilute aqueous base produced 3-methyl-1,2-benzisoxazole. The mechanism was reported to be a C(2)—C(3) ring closure via intermediate (560) (Scheme 171). Salicylaldehyde failed to cyclize with dilute base, but with 20% KOH and hydroxylamine-O-sulfonic acid the transformation to 1,2-benzisoxazole succeeded (76MI41600). Kemp and Woodward isolated an oxime sulfonate (561) from salicylaldehyde and hydroxylamine-O-sulfonic acid and the subsequent decomposition gave 1,2-benzisoxazole in 95% yield (65T3019). 

The reaction of vinylogous amides, or ketoaldehydes, with hydroxylamine produced 4,5,6,7-tetrahydro-l,2-benzisoxazole. A side product is the 2,1-benzisoxazole (Scheme 173) (67AHC(8)277). The ring system can also be prepared by the reaction of cyclohexanone enamines with nitrile oxides (Scheme 173) (78S43, 74KGS901). Base treatment produced ring fission products and photolysis resulted in isomerization to benzoxazoles (76JOC13). 

The synthesis of this series involved the reaction of disubstituted or benzo fused 6-keto(formyl)-2-cyclohexenones with hydroxylamine (Scheme 176), Base degradation gave a-cyanoketones which can be further degraded to diacids (67AHC(8)277, 80IJC(B)406). 

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