Nitrile postulated mechanism

Two possible mechanisms for the formation of product 89 have been proposed. One postulated mechanism involves the oxidation of the indole ring of compound 87, thereby producing the corresponding 3-hydroxy intermediate 90, which then reacts with the dipole 88 to produce the observed product 89 (Scheme 22). Alternatively, nucleophilic addition of the indole nitrogen to the nitrile oxide 89, followed by oxidative ring closure of the resulting intermediate 91 would also account for the formation of the cyclized product 90. The authors favor the dipolar cycloaddition route in which the oxidized indole species 90 is the dipolarophile. The authors claim this mechanism is supported by the observation that when 90 (n = 4) is independently synthesized and isolated, its cycloaddition with dipoles yields identical products. 

The addition of aryl azides to a-cyanoacrylic esters, nitriles, and amides, leads in each case to a pyrrolidine (94). The postulated mechanism involves the expected triazoline intermediate (95) which gives the ylide (96) followed by a second cycloaddition. 

When zeolites were placed in the reactor, benzaldehyde again completely disappeared, but benzonitrile was formed. Its yield depended slightly on the reaction temperature. In contrast to the reaction of chlorobenzene and ammonia, the yield of benzonitrile depended only slightly on the kind of metal cations, as seen in Table II. This suggests that the rate-determining step of the nitrile formation does not involve metal cations. The reaction mechanism is postulated as follows ... 

The controversy between Huisgen and Firestone concerning the mechanism for 1,3-dipolar cycloaddition is longstanding.9,11 For nitrile oxide cycloadditions, experimental data have been interpreted either as supportive of a concerted mechanism9 or in favor of a stepwise mechanism with diradical intermediates.11 Theory has compounded, rather than resolved, this problem. Ab initio calculations on the reaction of fulmonitrile oxide with acetylene predict a concerted mechanism at the molecular otbital level,12,13 but a stepwise mechanism after inclusion of extensive electron correlation.14 MNDO predicts a stepwise mechanism with a diradical intermediate.13 The existence of an extended diradical intermediate such as (4 Scheme 2) has been postulated by Firestone in order to account for the occasional formation of 1,4-addition products such as the oxime (5).11 Of course, the intermediates (4) and (5) for the Firestone mechanism do not correspond to the initial transition states in Firestone s theory. These are attained prior to the formation of, and at higher energy than, the intermediates. 

In a recently reported synthesis of pyridines, lithiated methoxyallenes react with nitriles in the presence of trifluoroacetic acid (Scheme 107) <2004CEJ4283>. The mechanism is postulated to proceed via initial protonation followed by nucleophilic addition of the trifluoroacetate ion with subsequent intramolecular acyl transfer and aldol condensation to give the pyridine. An additional pyridine formation starting from azaenyne allenes forms a-5-didehydro-3-picoline diradicals, which can be trapped by 1,4-cyclohexadiene, chloroform, and methanol to produce various pyridines <20040L2059>. 

The base catalyzed reaction of 4-phenyl-l,2-dithiole-3-thione 506 with a,P-unsaturated nitriles affords 6-aminothiopyran-2-thiones. A complex mechanism is postulated for the transformation with elimination of a thioketone from a dithiepin featuring in the key step (Scheme 189) <2003PS(178)2255>. 

The photochemical alkylation of olefins by nitriles and ketones is not straightforward, due mainly to the inefficient abstraction of hydrogen from an electron-withdrawing-substituted carbon by an electrophile such as the photocatalyst excited state. Nevertheless, various methyl ketones have been synthesized by the irradiation of a ketone/oleftn mixture dissolved in aqueous acetone. The mechanism of the reaction remains to be clarified, but a water-assisted C—C coupling between an acetonyl radical and the olefin has been postulated (Scheme 3.12). The reaction has several advantages, as it is cheap (an acetone/water mixture is used as the solvent) and occurs under mild metal-free conditions with no need for a photocatalyst [28],... 

Huisgen and co-workers reported, in three papers (02T507, 02T4185 and 02HCA1523> the conversion of various 1,3,4-thiadiazolines 86 into thiocarbonyl ylides 87 via extrusion of N2. They then described cycloaddition reactions of these ylides 87 with various a,P-unsaturated esters and nitriles and postulated reaction mechanisms for the regioselectivity and stereochemistries observed in the transformations. 

In consideration of conceivable strategies for the more direct construction of these derivatives, nitriles can be regarded as simple starting materials with which the 3+2 cycloaddition of acylcarbenes would, in a formal sense, provide the desired oxazoles. Oxazoles, in fact, have previously been obtained by the reaction of diazocarbonyl compounds with nitriles through the use of boron trifluoride etherate as a Lewis acid promoter. Other methods for attaining oxazoles involve thermal, photochemical, or metal-catalyzed conditions.12 Several recent studies have indicated that many types of rhodium-catalyzed reactions of diazocarbonyl compounds proceed via formation of electrophilic rhodium carbene complexes as key intermediates rather than free carbenes or other types of reactive intermediates.13 If this postulate holds for the reactions described here, then the mechanism outlined in Scheme 2 may be proposed, in which the carbene complex 3 and the adduct 4 are formed as intermediates.14... 

Ab initio calculations performed by Bigot and Roux have led to an alternative mechanism involving two photochemical steps and the intermediacy of an azirine, as shown in Scheme 40 . Hydrogen atom transfer from the enamine nitrogen to the nitrile carbon of 173 would generate diradical intermediate 177, which would then collapse to the postulated azirine 178. In a second photochemical step, the azirine would then undergo carbon-carbon bond homolysis to 179 followed by reclosure to the imidazole 176. In support of this proposed second photochemical step, structurally similar azirines have been shown to undergo facile carbon-carbon bond photolysis . This mechanism does not, however, explain the initial formation of a thermally unstable intermediate with the observed IR stretch, since azirines of this type are thermally stable at room temperature . ... 

The basic hydrolysis of nitrile 50 with aqueous NaOH in ethanol was examined, which proceeded throngh intermediate amides 57, and reached 98% conversion to acid 3 within 4 hr with <1% of amides remaining. Both cis- and trans-amides were observed by liqnid chromatogra-phy/mass spectrometry (LC/MS) during reaction, and the strnctnre of trans-amide 571 was con-hrmed by LC/MS and independent synthesis (by treatment of trani-pyrrolidine acid with CDI and ammoninm hydroxide). It is reasonable to postulate that the hydrolysis of both di-nitrile 50 and di-amide 57c to the corresponding di-acids was slow relative to epimerization, which provided a mechanism for complete conversion of di-nitrile 50 to trani-acid 3. 

Similar mechanisms are postulated for commercial alkene/arene, carbonyl and nitrile hydrogenations on metal surfaces in particular, individual metal atoms are involved. In contrast hydrogenolysis, the cleavage of C—C or C—O (N, S, etc.) bonds, appears to need two or more adjacent sites and can sometimes be reduced by alloying the main component (addition of copper to nickel, for example). The stability of supported metal (especially platinum) catalysts permits their use at high temperatures, to promote hydrogen transfers between alkanes, alkenes and arenes or dehydrogenation processes. 

Casale and Porter (1975) reported that copolymer formation between NBR and PVC may occur via mechanochemical radical generation on each polymer followed by recombination. The proposed mechanism was based on earlier studies by Akutin (1968). Later, Manoj et al. (1993b) postulated another mechanism for the same system involving hydrolysis of nitrile groups to amide or carboxylic acid followed by displacement of allylic chloride on PVC by amide-NH2 or acid-OH. 

In the chemistry of polyhedral boron hydrides, boron-centered cations were postulated to be key intermediates of an electrophile-induced nucleophilic substitution mechanism that is responsible for the formation of a variety of boron-substituted derivatives [14], Such boron-centered cations can be easily generated by abstraction of a hydride by the treatment of polyhedral boron hydrides with Lewis or Bronsted acids [15], Similar to the classical chelate-restrained borinium cations based on 3-coordinate boron, these species, which we called quasi-borinium cations, have an unstabilized p orbital and are strong electrophiles (Scheme 6.1). Such quasi-borinium cations are highly reactive and react with even weak nucleophiles, such as ether or nitrile solvent molecules giving the corresponding oxonium and nitrilium derivatives whose properties are close to those of similar complexes of transition metals [15-17]. 

Mahadevan and Thimann [43] postulated the first nitrilase reaction mechanism, suggesting that the nitrile carbon present in the substrate displays a partial positive charge that is subjed to nudeophihc attack by one of the two SH groups in the nitrilase active site. The resulting thioimidate is then hydrolyzed to a thioester, with the release of ammonia as a by-product Hydrolysis of the acyl-enzyme then results in the release of the final acid product. 

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