Chlorination of aldoximes

A method that avoids the conventional chlorination of aldoximes corresponds to the reaction of nitroalkanes or conjugate nitroalkenes with titanium tetrachloride (48) (Scheme 6.3). a-Chloro (a), alkyl (a, b, c), aryl (c), a-cyano (d), and a-azido (d) hydroximoyl chlorides have been prepared in good yield in this way (48). Concerning overall efficiency, however, this would necessitate that the nitro... 

Chlorination of aldoximes. NCS converts aryl aldoximes to hydroxamic acid chlorides without significant chlorination of the aryl group. This reaction has been used for a novel synthesis of nitrile oxides. Thus reaction of salicylaldoxime (1) with NCS followed by dehydrochlorination with pyridine generates a nitrile oxide, which is trapped by styrene to give the isoxazoline 2. The N-O bond can be cleaved by catalytic hydrogenation to 3, which is converted into the chalcone 4 on elimination of water. This product can be converted by classical methods to the flavanone 5 and the flavone 6. An analogous route can be used to synthesize 2-... 

Hydroximoyl chlorides. Chlorination of aldoximes by this reagent at room temperature is rapid. 

The chlorination of aldoximes I is the classical method of synthesis of hydroxamoyl chlorides II. Werner and his co-workers in 1894 ( 5-69 this method to synthesize a variety of aromatic hydroxamoyl chlorides. 

This reaction resembles the direct chlorination of aldoximes, which yields hydroxamoyl chlorides (see Chapter 6). 

Another methodology for the in situ preparation of nitrile oxide is the dehydro-halogenation of hydroxymoyl chlorides vrith triethylamine. Hydroxymoyl chlorides are accessible by the reaction of aldoximes vrith chlorinating agents such as NCS (N-chlorosuccinimide). Isoxazolines of C50 and C70 [293-295] with R = Ph, alkyl, 4-C5H4OCH3 4-C5H4CHO, amino acid [305], dialkoxyphosphoryl [296, 297] or ferrocene [298] have been synthesized in ca. 20 0% yields. The latter reaction is slower than the dehydration of nitroalkanes and requires one equivalent of hydroxymoyl chloride whereas excess nitroalkane is necessary for an optimum reaction [293]. 

Chloramine-T has also been employed, both as a halogenating reagent and base the reaction proceeds in good yield with aromatic as well as with aliphatic aldoximes (81). The role of chloramine-T probably involves an initial chlorination of the aldoxime to give the hydroximoyl chloride, followed by base-catalyzed hydrogen chloride elimination to afford the nitrile oxide (81). 

Nitrile oxides could also be prepared from nitroalkanes by reaction with (Boc)20 in the presence of catalytic amounts of DMAP at room temperature under N2 [276]. Alternatively they could also be prepared via base-induced dehydrohalogenation from hydroximinoyl chlorides, which can be either purchased or generated hy chlorination of the corresponding aldoximes with N-chlorosucdnimide. 

Bis(trichloromethyl) carbons Dehydration. Aldoximes Et.fN to give nitriles in good >1 Chlorination of phosphim dichlorides on reaction with lri to 1,2-dichloroalkanes, aldehyd to i.sonitriles, ureas to carbodii... 

There are comparatively very few kinetic studies of beta-eliminations giving imines or nitriles. Nitriles can be prepared by the acid-catalysed dehydration of amides or aldoximes or by the base-catalysed elimination from aldochlor-imines or esters of aldoximes. Imines often result in the attempted preparation of A-chloramines, dehalogenation occurring in the weakly alkaline hypochlorite solution which is used as the chlorinating reagent. 

The Ponzio reaction provides a useful route to gem-dinitro compounds and involves treating oximes with a solution of nitrogen dioxide or its dimer in diethyl ether or a chlorinated solvent. The Ponzio reaction works best for aromatic oximes where the synthesis of many substituted aryldinitromethanes have been reported. Compound (56), an isomer of TNT, is formed from the reaction of dinitrogen tetroxide with the oxime of benzaldehyde (55) followed by mononitration of the aromatic ring with mixed acid. Yields are usually much lower for aliphatic aldoximes and ketoximes. " The parent carbonyl compound of the oxime is usually the major by-product in these reactions. 

In Table 2 are listed the hydroxylamines, oximes and hydroxamic acids for which we have determined the gas phase structures. We tried to select a representative group in each category. There are two types of oximes, as indicated, aldoximes and ketoximes. Due to restricted rotation around the C=N double bond, these can exist in two isomeric forms (except when R = H for an aldoxime and R = R" for a ketoxime). We have investigated both isomers in nearly every instance. For aldoximes, they are generally labeled syn when the H and OH are on the same side of the double bond and anti when on opposite sides. Note that the ketoximes in Table 2 contain one pair of isomers in which the >C=NOH group is not bonded to two carbons instead one bond is to a chlorine. One of these isomers wiU be of interest in Section B.D in the context of hydrogen bonding vi lone pair—lone pair repulsion. 

Hydroximoyl halides (4) are conveniently prepared by halogenation of the respective aldoximes (5), for which a number of halogenating agents such as chlorine (38), ferf-butyl hypochlorite, A -chlorosuccinimide (NCS) (39), or A -bromosuccin-imide (NBS) (40) have been employed. A plausible mechanistic course involves Hal addition and proton loss to give an a-halonitroso compound, often observed as a transient blue-green color, as shown for the chloro case (Scheme 6.1). 

When R (in 60) was a chlorine atom, the conditions were slightly modified to prevent its hydrolysis. The conversion of a methyl group (in R ) to an aldoxime (see Section 1) was found avoidable by a modification as was the hydrolysis of a 2-primary amino group (R ) to an 8-aza-purin-2-one. ... 

Oxidation of nitrogenous compounds. Both ketoximes and secondary nitro-alkanes are oxidized to ketones. Aldoximes are converted to nitroalkanes, but nitriles are formed under different conditions. In the presence of a chlorine source (NaCl, HQ) ketoximes give a-chloronitroaUcanes and nitroalkenes give the a-chlorinated products. ... 

The addition of nitrile oxides to a,P-unsaturated carboxylic acid derivatives opens up a route to chiral, substituted isoxazoline derivatives. The nitrile oxides are generated in situ via deprotonation with a base (e.g. triethylamine) starting from the chlorinated aldoxime as the precursor (solvents CHCI3, CH2CI2, ether, benzene, toluene temperature -78°C up to 110°C). In most cases only one of two possible regioisomeric adducts is formed. 

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