Nitriles amidoximes

The cyclization step, whereby Pt(IV)-mediated nitrile-amidoxime coupling leads to 1,2,4-oxadiazoles (14), is promoted by strong acceptor substituents R and unaffected by the metal centre (Scheme 14). ... 

Condensation of diazonium salts 1152 with activated nitriles provides hydrazones 1153. Treatment of hydrazones 1153 with hydroxylamine affords amidoximes 1154 in high yield. Upon heating with anhydrous sodium acetate in refluxing DMF, compounds 1154 undergo intramolecular cyclocondensation to provide 5-substituted 4-amino-2-aryl-277-1,2,3-triazoles 1155 in 75-85% yield (Scheme 190) <2006ARK(xv)53>. 

Microwave irradiation of amidoximes in the presence of an aldehydes under solvent-free conditions has been reported to give fully conjugated 1,2,4-oxadiazoles directly, a process that is notable because the amidoximes can be prepared in the same reaction vessel from a nitrile and hydroxylamine (Scheme 33) <2006TL2965>. 

The cycloaddition of nitrile oxides to amidoximes 234 leads to 1,2,4-oxadiazole 4-oxides which can then be deoxygenated with trimethyl phosphite (Equation 48) <1997T1787>. 

In a similar approach (Equation 53), the use of a resin-bound nitrile allowed access to the corresponding resin-bound amidoximes 274, which could be converted into 1,2,4-oxadiazoles 275 via acylation with either an appropriate acid halide/ anhydride in the presence of a base or a carboxylic acid in the presence of a coupling reagent followed by cyclization, where the latter step was performed by heating in pyridine or diglyme and could be accelerated by the use of a microwave oven. Cleavage from the resin was easily achieved by the use of TFA in dichloromethane <2000BML1431>. 

Rice and Nuss report that the Argopore MB-CHO polymer-supported amidoximes 282 (readily available from the nitrile 281), shown in Scheme 46, can be acylated with acid chlorides in the presence of excess pyridine to give the O-acylamidoximes 283. Cyclization was carried out with TBAF in THF at ambient temperature, to give the polymer-supported 1,2,4-oxadiazoles 284. Release of the 1,2,4-oxadiazoles 285 from the polymer support was achieved by treatment with 95% trifluoroacetic acid <2001BML753>. 

The conversion of the polystyrene-supported selenyl bromide 289 into the corresponding acid 290 allowed dicyclohexylcarbodiimide (DCC)-mediated coupling with an amidoxime to give the 1,2,4-oxadiazolyl-substituted selenium resin 291 (Scheme 48). Reaction with lithium diisopropylamide (LDA) and allylation gave the a-sub-stituted selenium resin 292, which was then used as an alkene substrate for 1,3-dipolar cycloaddition with nitrile oxides. Cleavage of heterocycles 293 from the resin was executed in an elegant manner via selenoxide syn-elimination from the resin <2005JC0726>. 

Nitrile oxides add to various N-nucleophiles, bearing N-H bonds to give amidoximes. These nucleophiles comprise primary and secondary amines, amides, N-heterocycles and so on. Thus, N-unsubstituted pyrazole, imidazole, 1,2,3- and... 

Interesting examples of the addition of N-nucleophiles to nitrile oxides are syntheses of chelated Z-amidoxime, N-[2-(dimethylaminomethyl)phenyl]mesitylene-carboamidoxime (118), and pyranosyl amidoximes (119) from the respective nitrile oxides and amines. Aromatic aldoximes undergo unusual reactions with chloramine-T (4 equiv, in refluxing MeOH). N-(p-toly 1 )-N-(p-tosy 1 )benzamides are formed via addition of 2 equiv of chloramine-T to the intermediate nitrile oxide followed by elimination of sulfur dioxide (120). 

Addition of ammonia as a model nucleophile to nitrile oxides was studied by a semiempirical MNDO method, for fulminic acid and acetonitrile oxide (121). The reaction is exothermic and proceeds in two steps. The first (and rate-determining) step is the formation of a zwitterionic structure as intermediate. The second step, which involves transfer of a proton, is very fast and leads to the formation of Z-amidoximes in accordance with experimental data. Similar results were... 

Oxadiazoles can be sucessfully obtained from amidoximes and diethyl carbonate/ f-BuOK °, triethyl orthoformate/BFs OEtg or by reaction of hydroximoyl chlorides with nitriles . ... 

The first examples of furazan and furoxan nitrile oxides have been reported in the early 1990s. 4-Aminofurazan-3-carbonitrile oxide (65) was generated from the hydroximoyl chloride with base and its cycloaddition reactions investigated <92KGS687>, and the 4-phenyl analogue (66) is formed via the nitrolic acid derivative by treatment of the aldoxime with dinitrogen tetroxide <93LA44i>. Furazan-3-amidoximes react in the usual way with nitriles to yield 3-(furazan-3-yl)-1,2,4-oxadiazoles <9013941 >. 

In another cyclization procedure for the 1,5-benzodiazodne system, the nitriles (296) are converted to the aminodihydrodiazocines (297) (79CPB2589). Attack of nucleophiles on (297) occurs at the N-5—C-6 bond to give the 3,4,5,6-tetrahydrodiazodnes (298) with NaBH4 and the jS-aminoethylquinazolines (301) on hydrolysis. The diazocines (297) behave as typical amidines. Oxidation leads to the amidoximes (300) which on hydrolysis are converted to 2,1-benzisoxazoles (302), and reaction with diketene leads to the fused pyrimidinones (299 and l-methyl-3-one isomer) (79CPB2927). 

Many variations on the pathway represented by Eq. (1) are successful. For example, the amidoxime can be made by heating a nitrile with hydroxylamine hydrochloride10-17 and in other ways. 

The butadiene (80%)-acrylonitrile(17%)-aerylamidoxime(3%) terpolymer was prepared by reacting 2.5g butadiene 80%)-acrylo-nitrile(20%) copolymer (Aldrich) in 150 ml xylene with 1.61g hydro-xylamine hydrochloride in 12 ml n-butanol (freed of HC1 immediately before addition by method of Hurd (4) by dropwise addition under nitrogen. Reaction time and temperature were 23 hr. and 90-95°C. The polymer product was worked up by slowly adding the reaction mixture to 500 ml ether with rapid stirring. The precipitated polymer was allowed to settle, the supernate decanted and the polymer resuspended and washed with two 100 ml portions of ether followed by vacuum drying. Yield 2.04g (81%). Conversion of nitrile functional groups to amidoxime groups was 15% by infrared absorption. 

The relative initial ratio of acrylonitrile to butadiene and degree of conversion of nitrile to amidoxime are directly related to the resultant film s solubility parameter and glass transition temperature. Ideally, the concentration of amidoxime functional groups would be maximized while the coating s solubility parameter is matched to the vapor to be detected and the glass transition temperature is kept below room temperature. In practice, the conversion limitations are set by the reaction conditions of limited polymer solubility, reaction temperature and time. Three terpolymers of varying butadiene, acrylonitrile and amidoxime compositions were prepared as indicated in Table 1. 

Amidoximes can be prepared by acid-catalysed additon of hydroxylamine to nitriles. 

Amidoximes (155) may be made by heating a nitrile (154) with hydroxylamine in acid solution. The sulfone function does not interfere with subsequent ring formation (79JHC1197). Amidoximes (158) may also be of an aldoxime (156) followed by ammonolysis of the oximinochloride (157). 

A few 6- and 8-cyanopurines have been prepared and undergo characteristic nitrile addition reactions rather readily. Thus, alkaline hydrolysis produces carboxamides, then carboxylic acids, alcoholysis leads to imidates, ammonolysis to amidines, hydrazinolysis to amidhydrazines, hydroxylamine to amidoximes, and hydrogen sulfide to thioamides. Acid hydrolysis tends to give the decarboxylated acid derivative. Reduction either by sodium-ethanol or, preferably, by catalytic hydrogenation affords aminoalkylpurines and addition of Grignard reagents produces, in the first place, acylpurines. As with aldehydes, most of the compounds examined have been relatively non-polar derivatives. Table 28 lists some reactions and relevant literature. 

First used by Tiemann, method A, the reaction of hydroxyl-amine with nitriles, has been the one used most often. Tiemann and Kruger were the first to show the simultaneous presence of the —NH2 and =NOH groups in an amidoxime, benzamidoxime. Method A is described in this preparation. 

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