Nitriles reactions with hypochlorite

Nickel peroxide is a solid, insoluble oxidant prepared by reaction of nickel (II) salts with hypochlorite or ozone in aqueous alkaline solution. This reagent when used in nonpolar medium is similar to, but more reactive than, activated manganese dioxide in selectively oxidizing allylic or acetylenic alcohols. It also reacts rapidly with amines, phenols, hydrazones and sulfides so that selective oxidation of allylic alcohols in the presence of these functionalities may not be possible. In basic media the oxidizing power of nickel peroxide is increased and saturated primary alcohols can be oxidized directly to carboxylic acids. In the presence of ammonia at —20°, primary allylic alcohols give amides while at elevated temperatures nitriles are formed. At elevated temperatures efficient cleavage of a-glycols, a-ketols... 

Preparation of the prototype drug departs from the phenylenediamine strategy used in all of the previous examples. Condensation of thiazolo nitrile (53-2) with aniline catalyzed by aluminum chloride affords the amidine addition product (53-3). This is then converted to its reactive A -chloro derivative (53-4) by reaction with sodium hypochlorite. Treatment of that intermediate with a base such as potassium hydroxide leads directly to the cyclization product and thus the benzimidazole thiabendazole (53-6) [56]. The reaction can be rationalized by invoking as the first step the abstraction of chloride to leave behind a nitrene species such as (53-5) this would then readily insert in the CH bond at the ortho position. 

In related fashion, the oximes of the aldehydo compound 68, following reaction with sodium hypochlorite, form the corresponding nitrile oxide 71 and, hence, afford the isoxazolines 72 in 86% yield as a 64 36 mixture (see Scheme 17) [35]. Here, the main... 

DOT CLASSIFICATION 6.1 Label KEEP AWAY FROM FOOD SAFETY PROFILE Poison by ingestion, inhalation, skin contact, subcutaneous, and intraperitoneal routes. A skin irritant. Explosive reaction with sodium hypochlorite. Used in production of drugs of abuse. When heated to decomposition it emits very toxic fumes of CN and NO. See also NITRILES. 

BENZYL NITRILE (140-29-4) Combustible oily liquid (flash point 215°F/102°C). Violent reaction with acids, forming hydrogen cyanide. Violent reaction with sodium hypochlorite. 

We have recently applied this technique to a study of the oxidative metabolism of several drugs (Schemes 29.26 to 29.29). Reactions with tetrakis(2,6-dichlorophenyl)porphyrin Fe(ni)Cl, octachlorotetrakis(2,6-dichlorophenyl)porphyrin Fe(III)Cl, and octabromotetra-kis(2,6-dichlorophenyl)porphyrin Fe(III)Cl were conducted in methylene chloride-water or water-acetone to nitrile (80 20 v/v) at ambient temperatures. lodosobenzene, cumene hydroperoxide, hydrogen peroxide, or sodium hypochlorite was used as the source of... 

Under radical conditions, aldehydes are readily oxidized hy NBS to acid bromides. The oxidation of aldoximes to nitrile oxides using NBS and Triethylamine in DMF is superior to the use of aqueous hypochlorite. Tosylhydrazones are cleaved by reaction with NBS in methanol, and hydrazines and hydrazides are oxidized to azo cort5)ounds. ... 

The 1,3-dipolar character of triazaallenium salts, from now on referred to as l,3-diaza-2-azoniaallene salts, is evidenced by the many [3+2] cycloaddition reactions these types of compounds can participate in. The l,3-diaza-2-azoniaallene salts are generated in situ and trapped with suitable dipolarophiles. For example, l,3-diaza-2-azoniaallene salts undergo stereospecific [3+2] cycloaddition reactions with alkynes and olefins. However, they fail to react with isocyanates, isothiocyanates and azo compounds. Also, [3+2] cycloadditions to carbodiimides and cyanamides are observed. In contrast, nitriles fail to react. 1,3-Diaza-2-azoniaallene salts are obtained in the oxidation of 1,3-disubstituted triazenes with t-butyl hypochlorite. The resultant Al-chlorotriazenes react with antimony pentachloride to form the salts as reactive intermediates. Above —25°C, l,3-diaza-2-azoniaaUene salts disproportionate into diazonium salts and azo compounds. 

The intramolecular cycloaddition of a nitrile oxide (a 1,3-dipole) to an alkene is ideally suited for the regio- and stereocontrolled synthesis of fused polycyclic isoxazolines.16 The simultaneous creation of two new rings and the synthetic versatility of the isoxa-zoline substructure contribute significantly to the popularity of this cycloaddition process in organic synthesis. In spite of its high degree of functionalization, aldoxime 32 was regarded as a viable substrate for an intramolecular 1,3-dipolar cycloaddition reaction. Indeed, treatment of 32 (see Scheme 17) with sodium hypochlorite... 

The most widely used, and often most convenient reagents for such one-pot reactions are sodium hypochlorite (45) or hypobromite (16). These reactions are performed in the presence of an organic base (generally triethylamine) that normally enhances the yield of cycloaddition products (45). This method was employed for many intermolecular reactions (71) and also seems especially suited for intramolecular ones (72-77) as well as for the solid-phase synthesis (78) of 2-isoxazolines. Hypohalite can also be replaced by sodium broruite in combination with a catalytic amount of tri-u-butyltin chloride (79). In a related method, O-tributylstannyl oximes were treated with tert-butyl hypochlorite to produce nitrile oxides that were trapped with aUcenes or alkynes to afford the corresponding isoxazolines or isoxazoles in moderate to good yield (80). 

Recently, the intramolecular nitrile oxide-alkene cycloaddition sequence was used to prepare spiro- w(isoxazolines), which are considered useful as chiral ligands for asymmetric synthesis (321). Reaction of the dibutenyl-dioxime (164) (derived from the diester 163) with sodium hypochlorite afforded a mixture of diastereomeric isoxazolines 165-167 in 74% combined yield (Scheme 6.80) (321). It was discovered that a catalytic amount of the Cu(II) complex 165-Cu(acac)2, where acac = acetylacetonate, significantly accelerated the reaction of diisopropylzinc... 

Small Quantities (White Phosphorus). Wear nitrile rubber gloves, laboratory coat, and eye protection. Work in the fume hood. Five g (0.16 mol) of white phosphorus are cut under water into 5mm pellets. The pellets are added to 800 mL (0.8 mol) of 1 M cupric sulfate (127.7 g or 199.7 g of CuS04 or CuS04-5H20, respectively, dissolved in 800 mL of water) solution in a 2-L beaker. The mixture is allowed to stand for about a week with occasional stirring. The phosphorus grad-ually disappears, and a fine black precipitate of copper and copper phosphide is formed. The reaction is complete when no waxy white phosphorus is observed when one of the pellets is cut under water. The precipitate is separated, and while still wet, transferred to 500 mL of laundry bleach (5% sodium hypochlorite), and then stirred for about 1 hour to ensure complete decomposition of copper phosphide. The solids are separated and packaged for disposal. The aqueous solution is washed into the drain.33... 

Small Quantities. Wear eye protection, laboratory coat, and nitrile rubber gloves. In the fume hood, add to an equal volume of sodium carbonate or calcium carbonate, and then add to a very large volume of water. Cautiously add calcium or sodium hypochlorite solution (household bleach). When reaction is complete (test with silver nitrate for completeness of reaction),8 dilute and neutralize. Let stand until solids settle. Liquid may be decanted into the drain with at least 50 times its volume of water. Solid residue may be discarded with normal refuse.6,7... 

Direct dehydrogenation of oximes is also possible, particularly for sterically hindered nitrile oxides. The most successful oxidizing agents are alkaline hypobromite and NBS in the presence of base, the latter being valuable when basic groups are present. Lead tetraacetate and alkaline hypochlorite have also been employed, but the yields are lower. The formation of furoxans from the reaction of alkoximes with nitrogen oxides is believed to proceed via the corresponding nitrolic acids. 

The synthesis of a series of isoxazoles 15 and isoxazolines 15a on the solid phase has been reported by Pei and Moos [50] via [3 + 2] cycloaddition of alkenes and alkynes with highly reactive nitrile oxides. The cycloaddition reactions of resin-bound peptoids were carried out in toluene at 100°C or in DCM-H2O at room temperature, depending on the precursors of the nitrile oxides. Benzaldehyde oxime and various nitroalkyl compounds were selected as nitrile oxide precursors. The nitrile oxides were generated in situ by reacting the nitroalkyl compounds with phenyl isocyanate and triethylam-ine or by oxidizing the oximes with sodium hypochlorite in the presence of triethylamine (Fig. 7). 

A stereocontrolled total synthesis of (+)-vinblastine (329), a prominent alkaloid used in cancer chemotherapy, was reported by the Fukuyama/ Tokuyama team and features an INOC reaction for the preparation of a key reaction intermediate utilized in their synthesis (2010CR101). Thus, the oxidation of oxime 323 with sodium hypochlorite generated the expected nitrile oxide 324 which imderwent a subsequent 1,3-dipolar cycloaddition to produce isoxazoline 325 as a single isomer (Scheme 59). The INOC proceeded via a six-membered chairlike transition state (i.e., 324) to furnish 325 with the desired stereochemistry. After reductive cleavage of the N—O bond in isoxazoftne 325 with zinc dust in acetic acid, a... 

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