Nitrile Oxides oxidative dehydrogenation

Aldoximes can be oxidatively dehydrogenated to nitrile oxides using a variety of oxidants such as lead tetraacetate [16a], alkali hypohalites [lla],NBS in DMF followed by base treatment [16b], chloramine-T [11b], 1-chlorobenzotriazole [16c], mercuric acetate [ 16 d], etc. However, we employed either NaOCl or chloramine-T for most of our INOC reactions. For instance, a piperidine ring fused to an isoxazoline as in 14 was constructed using the INOC methodology (Scheme 3) [17]. Monoalkylation of N-tosylallylamine 10 with the bromoacetal... 

The transformation of aldoximes to nitrile oxides is essentially a dehydrogenation... 

Different procedures of this dehydrogenation are thoroughly discussed in the monograph (4). It is only necessary to note here that the process is carried out mainly as halogenation-dehydrohalogenation. The intermediate hydroximoyl halide is frequently not isolated (Scheme 1.3). The reaction is convenient for both the generation of unstable nitrile oxides (in the presence of a dipolarophile) and the preparation of stable nitrile oxides. It is usually carried out in a two-phase water-organic solvent system with methylene dichloride as the preferred solvent. 

Several 4-(3-alkyl-2-isoxazolin-5-yl)phenol derivatives that possess liquid crystal properties have also been obtained (533-535). In particular, target compounds such as 463 (R = pentyl, nonyl) have been prepared by the reaction of 4-acetoxystyrene with the nitrile oxide derived from hexanal oxime, followed by alkaline hydrolysis of the acetate and esterification (535). A homologous series of 3-[4-alkyloxyphenyl]-5-[3,4-methylenedioxybenzyl]-2-isoxazolines, having chiral properties has been synthesized by the reaction of nitrile oxides, from the dehydrogenation of 4-alkyloxybenzaldoximes. These compounds exhibit cholesteric phase or chiral nematic phase (N ), smectic A (S4), and chiral smectic phases (Sc ), some at or just above room temperature (536). 

RuCl2(CO)3]j The oxidative dehydrogenation of a-hydroxy esters RCH(OH) COOR and cyanohydrins RCH(OH)(CN) to the corresponding a-keto esters and a-keto nitriles was effected by [RuCl3(CO)3]3/TBHP/CgHg, and the reaction was also catalysed by RuBrj, Ru(acac)3, RuClj(PPh3)3 and Ru3(CO)j2 [695],... 

A useful example is the oxidative dehydrogenation of primary amines to nitriles. The amine (2 mmol) is added dropwise or in small portions to a vigoronsly stirred solutuion of [RnO ] prepared as above (100 cm ) the reaction is complete when the dark orange colonr of [RuO ] reappears. The solution is extracted with dieth-ylether (3x25 cm ), dried over MgSO and the ether removed [549]. 

The dehydrogenation of appropriate stereo-isomers of monosubsti-tuted glyoximes yields nitrile-oxides which on heating are transformed into hydroxyoxadiazoles (3, 64). 

Cycloaddition reactions of nitrile oxides continue to be the source of new isoxazoles and dihydroisoxazoles. The oxidation of a-hydroxyimino acids 1 by ammonium hexanitratocerium(IV) has provided a new method of generation of benzonitrile oxide and other nitrile oxides on the other hand the oxime 2 is simply dehydrogenated by this oxidant to produce benzoylnitrile oxide <99BSJ2277>. Manganese dioxide has also been used to oxidise aldoximes to nitrile oxides the reaction is most efficient with methyl (hydroxyimino)acetate <99TL5605>. ... 

Oxidative dehydrogenation reactions of alcohols and amines are widespread in enzymatic biochemistry, and are of potential importance with regard to the operation of fuel cells based on simple alcohols such as methanol. The nature of products, and their rates of formation, may vary depending on the reaction conditions, and a role of metal ions has been recognized. The oxidation of amines may lead to a variety of products (nitriles, nitro species, etc.) although dehydrogenated diimine products are obtained quantitatively when the oxidation of the amine occurs via coordination to metal centers. A review is available on the mechanisms of oxidative dehydrogenations of coordinated amines and alcohols (93). 

Quite independently of Cornforth s efforts, a similar approach was designed and executed by Stevens and coworkers (75JA5940, 76T1599). The isoxazoles were synthesized by one of the three routes outlined in Scheme 25, in which primary nitro compounds are transformed into nitrile oxides by dehydration with either phosphoryl chloride or phenyl isocyanate, or else the same oxides were formed by dehydrogenation with LTA (syn product) or NBS (syn and anti). Reaction of the unstable nitrile oxides in situ with an appropriately substituted alkyne then afforded the isoxazole (294). 

Aldoximes from certain benzaldehydes were dehydrogenated to nitrile oxides by (dichloroiodo)benzene in hot chloroform with pyridine (or triethylamine). Since the products were not stable, they were isolated either in the form of dimers or as adducts with alkenes from 2-allyloxy-benzaldoxime an intramolecular adduct was obtained [55] ... 

The knowledge of the reaction mechanism is important for process design. Firstly, only olefins with activated methyl groups may undergo ammoxidation reactions to nitriles. Otherwise, oxidative dehydrogenation takes place preferentially. 

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 reaction differs from the Ritter reaction by the two types of electrophilic activation of the reagents and by the two types of rearrangement of nitrilium 285 and carboxonium ions 288 (equation 94). Besides, this interaction proceeds at an oxidation level of two, while the Ritter reaction occurs at an oxidation level of one17. While it may be shown that A-acyliminium ions 365 can be obtained from a carbonyl compound and a nitrile via the Ritter reaction, then it is only the second step b) in a three-step process where the first step (a) is the reduction of carbonyl compound 364 to alcohol 366 and the third step (c) is an oxidative dehydrogenation of amide 369 obtained3 (equation 105). 

As noted, alkynes are in general less reactive toward nitrile oxides than alkenes. They are also usually less readily available. It would therefore be useful to be able to carry out reactions between nitrile oxides and alkenes, and convert the resulting isoxazoline into the desired isoxazole. This goal can be achieved in two ways by using an alkene bearing a substituent which leads to ready elimination from the product and by dehydrogenating the product in a separate reaction (see Section II,D). 

Although isoxazoles can be obtained by cycloaddition of nitrile oxides to alkynes (Scheme 74), they are also accessible via the corresponding isoxazolines. Dehydrogenation of isoxazolines has been carried out... 

The reaction of enamines with nitrile oxides, forming hexahydro-(76) and tetrahydro- (77) indoxazenes,105 has been used to prepare indoxazenes and naphthoisoxazoles, by dehydrogenating the reduced derivatives using A-bromsuccinimide.340 Addition of cyanogen di-A-oxide to cyclohexa-1,4-diene gives di-3a,4,7,7a-tetrahydro-... 

The heterobimetallic complexes [N(n-Bu)4] [Os(N)R2(/u.-0)2Cr02] catalyze the selective oxidation of alcohols with molecular oxygen. A mechanism in which alcohol coordinates to the osmium center and is oxidized by B-hydrogen elimination (see -Hydride Elimination) is consistent with the data. The hydroxide adduct of OSO4, [0s(0H)204], with ferric cyanide and other co-oxidants catalyzes the oxidative dehydrogenation of primary aromatic and aliphatic amines to nitriles, the oxidation of primary alcohols to carboxylic acids, and of secondary alcohols to ketones. Osmium derivatives such as OsCb catalyze the effective oxidation of saturated hydrocarbons in acetonitrile through a radical mechanism. ... 

On the basis mainly of results obtained in the oxidation of isobutene to methacrolein, the oxidative dehydrogenation of butene to butadiene and the oxygen-aided dehydration of formamide to nitriles, it was possible to show that oxides present in catalysts are located on a scale reflecting donor-acceptor properties (fig. 5). Some oxides are essentially acceptors (e.g., M0O3, some tellurates) they can potentidly cany active and selective sites, provided they receive spillover oxygen. Others are essentidly donors a-Sb204, in this respect, is typical it produces spillover oxygen but carries no sites active for oxidation. Other oxides have mixed properties. The acceptors are relatively covalent, the donors are more ionic [63,77]. 

Valuable chemicals can principally be produced from paraffins if these unreactive compounds can be functionalized. This primarily requires the activation of the rather unreactive paraffinic C-H bond or C-C bond. Therefore, high temperatures are usually applied in the functionalization of paraffins. An interesting route is the partial oxidation of these compounds. This may yield olefins by oxidative dehydrogenation, oxygenates by oxygen insertion, or even nitrile compounds if a reactive nitrogen compound is added to the feed. 

Dehydrogenation of aromatic aldoximes to nitrile oxides [1, 80, before references]. N-Bromosuccinimide in dimethylformamide is an excellent reagent for the dehydrogenation of aromatic aldoximes to the corresponding nitrile oxides.17 Triethylamine serves well as base required to bind the hydrogen bromide eliminated since it is... 

Dehydrogenation of aromatic aldoximes.6 Unhindered aromatic nitrile oxides such as benzonitrile oxide (1) dimerize spontaneously to furoxazanes or 1,2,5-oxadiazole-1-oxides (2). If o.o -substituents are present, as in (3), they tend to inhibit dimeriza-... 

Nitrile oxides (R-C=N -0"), ° which can be generated by base-catalysed elimination of hydrogen halide from halo-oximes (RC(Hal)=NOH), or by dehydration of nitro componnds (RCH2NO2), readily add to alkenes and to alkynes, generating tive-membered heterocycles. Addition to an alkene produces an isoxazoline, unless the alkene also incorporates a group capable of being eliminated in a step after the cycloaddition, as shown below. However, isoxazolines can also be dehydrogenated to the aromatic system. ... 

Dihydro-l,2,4,5-oxatriazines have been obtained from reactions of nitrile oxides with hy-drazones,25,26 but their dehydrogenation was not attempted. 

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