Hydroxylamine supports

Hydroxylamine supported on magnesia reacted, under microwave irradiation, with nitriles and benzoyl chlorides to afford in a one-pot reaction 1,2,4-oxadiazoles <07TL2829>. In a stepwise procedure, amino acids and dicarboxylic acids were transformed into the corresponding 3,5-disubstituted 1,2,4-oxadiazoles, useful as peptidomimetic building blocks <07TL1465>. 

The reaction product of sahcylaldehyde and hydroxylamine, sahcylaldoxime, has been found to be effective in photography in the prevention of fogging of silver hahde emulsions on copper supports (96). It also forms the basis for an electrolytic facsimile-recording paper (97) and in combination with a cationic polymer, is used in another electrolytic dry-recording process (98) (see Electrophotography). 

In 1979, Olah [47] reported a one step conversion of alicyclic ketones into lactams by means of hydroxylamine O-sulfonic acid and formic acid under reflux for a few hours. More recently this reaction has been realized under solvent-free conditions with Si02 as inorganic support and focused irradiation, as exemplified in Scheme 8.29 for caprolactam synthesis. 

Polymer-bound 1-hydroxybenzotriazole 1008 reacts with carboxylic acids in the presence of 1,3-diisopropylcarbo-diimide (1,3-DIC) and DMAP to produce esters 1009. Treated with hydroxylamine, esters 1009 are converted to hydroxamic acids 1010 (Scheme 167) <20030BC850>. Starting 1-hydroxybenzotriazole 1008 is recycled in the process and can be used for other syntheses. This method is well suited for automated synthesis of a library of hydroxamic acids. In similar applications of polymer-supported 1-hydroxybenzotriazole 1008, a wide variety of amides is synthesized <1997JOC2594, 2002JC0576>. 

Each of the routes discussed thus far in this section are reliant upon amidoxime-based methods. In a change from this paradigm, Makara etal. produced the polymer-supported benzotriazoles 294 and converted them easily into the iV-acyl-177-benzotriazole 1-carboximidamides 295. Cyclization with hydroxylamine gave the supported 3-amino-l,2,4-oxadia-zoles 296 which were cleaved with TFA to give the free 3-amino-l,2,4-oxadiazoles 297 (Scheme 49) <2002TL5043>. 

The fact that hydroxylamine has been found among the products of transformations of nitroxyl radical during the oxidation of hydrocarbons is the evidence in support of this mechanism. Both mechanisms described earlier are realized in parallel and supplement each other. The result of the competition between them depends primarily on the temperature, because the thermal decomposition of alkoxyamine AmOR requires a fairly high activation energy (see Table 19.11). 

Condensation of aromatic or aliphatic esters with resin-supported acetyl carboxylic acids 28 followed by cyclisation with hydroxylamine, activation of the linker, and cleavage using amines, provided highly substituted isoxazoles 30 and 31. This general method gave products in excellent yields and purities in which the regioisomers ratio can be easily controlled . 

Study of the kinetics of the oxidation of asymmetric secondary hydroxylamines to nitrones with H2O2, catalyzed by methylrhenium trioxide, has led to the elucidation of the mechanism of the reaction (104). Full transformation of N,N -disubstituted hydroxylamines into nitrones upon treatment with H2O2 occurs on using polymeric heterogeneous catalysts such as polymer-supported methylrhenium trioxide systems (105). 

Hence, the implication of combinatorial chemistry for high throughput generation of structurally diverse hydroxamic acids is self-evident. Several solid-phase approaches for their syntheses have been reported,1 7-11 the majority of which are based on the anchoring of iV-hydroxyphthalimide onto an appropriate solid support. After hydrazine-mediated /V-dcprotcction, /V-acylation of the resin-bound hydroxylamine would yield the desired O-anchored hydroxamic acid, which is typically released by acidolysis. 

Ashland Chemical Company, a division of Ashland Inc., was CSI s primary customer for purified hydroxylamine solutions. Ashland used the hydroxylamine solutions in residue cleaners for the semiconductor industry. Ashland planned to purchase 2 million pounds of 50% hydroxylamine from CSI. In exchange for discounted pricing of future deliveries of hydroxylamine solutions, Ashland provided CSI with financial support ( 350,000) to purchase production equipment. By February 1999, CSI had approximately twenty full-time employees, ten of whom were assigned to the new production facility. 

Polymer-supported permthenate has also been used in two convergent pathways for the synthesis of isoxazoUdines with each route employing different starting materials in order to create the maximum structural diversity [73]. In the first route secondary hydroxylamines, readily prepared from amines by in situ treatment with dimethyldioxirane, were oxidized directly to nitrones using polymer-supported permthenate (PSP). Alternatively, primary alcohols were used as the... 

In 2002, Kanno and Taylor successfully developed a simple one-pot procedure using MnOi/NHiOMe-HCl for the conversion of activated primary alcohols into O-methyl oximes (Scheme 11). They also developed a modification using Amberlyst 15-supported alkoxylamines, which can be employed to prepare other types of 0-aUcyl oximes as well as the parent hydroxylamines. This latter procedure has been used as the cornerstone of an efficient synthesis of the antifungal natural product citaldoxime 11 (Scheme 11). Citaldoxime is an antifungal natural product first obtained as a radiation-induced stress metabolite of Citrus sinensis , and later isolated from the roots of several different citrus plants. ... 

Making use of a O-trityl-hydroxylamine linker, Meloni and Taddei reported the first example of Miller hydroxamate on solid phase (161, Scheme 73). /1-Lactams 162 and 163 were prepared on solid support starting from serine, threonine or other / -hydroxyacids derived from naturally occurring amino acids and a resin bonnd hydroxylamine 159. The ring closure of 160 was carried out under Mitsunobu conditions. 

The solid-phase synthesis of hydroxamic acids has been of interest in the recent chemical hterature . Typically, hydroxylamine derivatives are tethered to solid supports via the oxygen (Scheme 79), although immobilization through the nitrogen has also been observed. 

A-Hydroxyphthalimide 178 was used as a source of the hydroxylamine reacting with trityl chloride resin 182 in the presence of triethylamine to obtain the A-hydroxyphth-alimide derivative 183. This intermediate is transformed to the desired hydroxylamine resin 184 by treatment with hydrazine. The peptidic and peptidomimetic hydroxamic acids 185 and 186 were synthesized using the described solid-supported reagent (Scheme 82). 

Although several routes have been published for the preparation of hydroxamic acids on solid phase, these generally involve the preparation of a special linker to which hydrox-ylamine is attached. Dankwardt s approach obviates the need for special linkers or protecting groups, by displacing the desired hydroxamic acid from the resin directly using hydroxylamine, as illustrated in Scheme 86. CarboxyUc-acid-ester-linked, polymer-supported, Cbz-protected amino acids 195 (formed from 194) were displaced from the resin with aqueous hydroxylamine to provide the corresponding hydroxamic acids 196. 

Nevertheless, the direct nucleophilic displacement of support-bound carboxylates to prepare hydroxamates presents some limitations. For example, O-tert-butyldimethylsilyl-protected hydroxylamine displaces common acids from oxime resin however, further treatment with trifluoroacetic acid (TFA) is necessary to remove completely the silyl... 

Recently, a direct kinetic study on the amination of substituted phenyhnagnesium bromides using Af,Af-dimethyl O-mesitylenesulfonyl hydroxylamine 3b as amination reagent has been reported by Erdik and Ate Ulkii . Rate data, the Hammett relationship and activation entropy support an Sn2 displacement of the carbon nucleophile on the electrophilic nitrogen. These results are consistent with the competition kinetics for electrophilic amination of substituted phenyl Grignard reagents with O-methylhydroxylamine In. ... 

Neutral alumina-supported sodium hydrogen sulfate was also used as a heterogenous catalyst for the one pot conversion of ketones to a great variety of amides in the presence of hydroxylamine under microwave irradiation in solvent-free conditions . ... 

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