Nitriles nucleophilic attacks

Again, since mixtures of 2-oxazolines are obtained from nitriles and unsymmetrical epoxides,15 it does not seem likely in this case that a purely carbonium ion mechanism is involved, for this would require the formation of primary carbonium ions. An alternate possibility is that the nitrile nucleophilically attacks the oxonium salt (27) of the epoxide to give the nitrilium salts 28 and 29, which then cyclize, thus ... 

The Houben-Hoesch reaction proceeds via a straightforward electrophilic aromatic substitution mechanism. Following protonation or Lewis acid activation of the alkyl nitrile, nucleophilic attack by the electron-rich pyrrole selectively at C(2) produces the resonance stabilized intermediate 1. Elimination of H" reestablishes the aromaticity of the pyrrole, resulting in imine 2, which is rapidly hydrolyzed to produce the ketone 3. ... 

Isoxazoles unsubstituted in the 3-position react with hydroxide or ethoxide ions to give )3-keto nitriles (243) -> (244). This reaction involves nucleophilic attack at the 3-CH group. 1,2-Benzisoxazoles unsubstituted in the 3-position similarly readily give salicylyl nitriles (67AHC(8)277), and 5-phenyl-l,3,4-oxadiazole (245) is rapidly converted in alkaline solution into benzoylcyanamide (246) (61CI(L)292). A similar cleavage is known for 3-unsubstituted pyrazoles and indazoles the latter yield o-cyanoanilines. 

Ortho esters are one of the few derivatives that can be prepared from acids and esters that protect the carbonyl against nucleophilic attack by hydroxide or other strong nucleophiles such as Grignard reagents. In general, ortho esters are difficult to prepare directly from acids and are therefore more often prepared from the nitrile. Simple ortho esters derived from normal alcohols are the least stable in terms of acid stability and stability toward Grignard reagents, but as the ortho ester becomes more constrained, its stability increases. 

Nucleophilic attack by carbanion occurs in the reaction of 2-nitrobenzamides 154 treated with sodium ethoxide (72JCS(P1)835). The reaction mixtures usually contain small amounts of nitrile 155 and carboxamide 156, the product of decarboxylation 158 being usually the principal product (Scheme 24). The corresponding bromo derivatives under the used conditions did not react. 

The early stages of the reaction of the quaternary salt can be regarded as proceeding in a manner exactly analogous to that by which the isoxazoles themselves are degraded, the j8-oxoketene imine structure (148) being one mesomeric form of a compound which could alternatively be formulated as a nitrilium betaine. However, by contrast with the products from the isoxazoles (i.e., enolates of /3-keto-nitriles), this is electrically neutral and susceptible to further nucleophilic attack. 

This, naturally, results in an increased electrophilicity of the nitrile group and also creates favourable conditions for the nucleophilic attack of the mercapto anion and an easy addition of hydrogen sulfide in accordance with the above scheme. The activation energy of the thioamidation of the model compounds is much higher (for glutarodinitrile — 11,8 [49,4] and for trinitrile - 7,97 kcal/mol [33,4 kJ/mol]) than in PAN (6,18 kcal/mol [25,9 kJ/mol]). 

Firstly there is nucleophilic attack of the nitrile carbon atom by hydroxylamine. An amide oxime is produced this then forms an intensely colored complex with the iron(III) chloride. 

Head-to-head [2+2]photocycloaddition of 1,2-diarylethanediones and 2-aminopropene nitriles (CH2 C(CN)NR2) occurs to yield oxetanes 10 in moderate to good yields. The formation of only one diastereoisomer in each of the cases investigated is rationalized in terms of the most easily accessible and stabilized 1,4-diradical intermediate <95RTC498>. 2,3,4-Trisubstituted oxetanes 11 are obtained in high yield by intramolecular nucleophilic attack of the anion from certain 2-(l-alkoxyethyl)-3-substituted oxiranes <96JOC4466>. 

Numerous examples of nucleophilic attack on coordinated nitrile ligands are found in the literature, particularly when the transition metal is platinum(II).224 The nucleophilic attack of two equivalents of CIO I2CII20 on the electrophilic nitrile carbon atoms of both nitrile ligands in cis-or /r<7H.v-[PtC12(RCN)2] (R = Et, Prn, Pr1, Bu p-CF3C6H4, p- and o-MeC6H4) affords the corresponding A2-l,3-oxazoline complexes ((76) and (77), respectively), in which the heterocycle acts as a... 

The selectivity of RNH2 on M/A1203 and Raney catalysts decreased in the order Co Ni Ru>Rh>Pd>Pt. This order corresponds to the opposite sequence of reducibility of metal-oxides [8] and standard reduction potentials of metalions [9], The difference between Group VIII metals in selectivity to amines can probably been explained by the difference in the electronic properties of d-bands of metals [3], It is interacting to note that the formation of secondary amine, i.e. the nucleophilic addition of primary amine on the intermediate imine can also take place on the Group VIII metal itself. Therefore, the properties of the metal d-band could affect the reactivity of the imine and its interaction with the amine. One could expect that an electron enrichment of the metal d-band will decrease the electron donation from the unsaturated -C=NH system, and the nucleophilic attack at the C atom by the amine [3], Correlation between selectivity of metals in nitrile hydrogenation and their electronic properties will be published elsewhere. 

This chapter, therefore, ends the monograph with a potpourri of reactions all of which occur without a change in oxidation state. In many cases, the reaction is one of nucleophilic attack at an electrophilic C-atom. The result is often hydrolytic bond cleavage (e.g., in carbohydrate conjugates, disubstitut-ed methylene and methine groups, imines, oximes, isocyanates, and nitriles, and various ring systems) or a nucleophilic substitution (e.g., hydrolytic de-halogenation of halocarbons and chloroplatin derivatives, and cyclization reactions). The formation of multiple bonds by dehydration is a special case to be discussed separately. 

The main theme to be appreciated here is that nucleophilic attack onto the nitrile triple bond can be interpreted mechanistically by extrapolation from carbonyl chemistry. 

The sequence can be rationalized mechanistically as involving nucleophilic attack of ammonia onto the aldehyde to produce an imine, which then acts as the electrophile for further nucleophilic attack, this time by the cyanide ion (see Section 7.7.1). The racemic amino acid is then formed by acid-catalysed hydrolysis of the nitrile function, as above (Box 7.9). 

New catalyst design further highlights the utility of the scaffold and functional moieties of the Cinchona alkaloids. his-Cinchona alkaloid derivative 43 was developed by Corey [49] for enantioselective dihydroxylation of olefins with OsO. The catalyst was later employed in the Strecker hydrocyanation of iV-allyl aldimines. The mechanistic logic behind the catalyst for the Strecker reaction presents a chiral ammonium salt of the catalyst 43 (in the presence of a conjugate acid) that would stabilize the aldimine already activated via hydrogen-bonding to the protonated quinuclidine moiety. Nucleophilic attack by cyanide ion to the imine would give an a-amino nitrile product (Scheme 10). 

The abovementioned transformation proceeds via initial formation of a,p-unsat-urated imines 114 from the starting aromatic nitriles, which then undergo the further nucleophilic attack at C3 atom by the exocyclic amino group of aminoazole followed by the cycUzation and aromatization and yielding the observed products 113 (Scheme 53). 

The furoxan ring is more susceptible to nucleophilic attack and reduction than it is to reaction with electrophiles or oxidation. Grignard reagents react with disubstituted furoxans primarily at C-3 and, in most cases, the resulting adduct fragments to a nitrile and a nitronate salt which affords a ketone on workup. 

Nitrile imines also undergo nucleophilic attack by enamines [e.g., the ketene aminals (386) that react to give the pyrazoles 388 (221)]. The intermediate adduct... 

Diazo compounds generally do not undergo [3 + 2] cycloaddition with unactivated nitriles under purely thermal, noncatalyzed conditions. The formation of 4-R-5-trimethylsilyl-l//-l,2,3-triazoles from the reaction of diazo(trimethylsilyl)-methyl lithium and a broad range of nitriles [RCN R = alkyl, aryl, SEt, OPh, PO(OEt)2] appears to be an exception, but this reaction most likely occurs in a stepwise manner with initial nucleophilic attack at the nitrile (275). 

Nucleophilic attack on a nitrile rather than a carbonyl has also provided aminopyrimidines as reported by Hassanien and co-workers in their efforts to discover new sulfonamide drugs <99JCR(S)8>. The reactions of sulfonamides 12 with a variety of nitrogen-based nucleophiles produced aminopyrimidines 13. 

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