Anilines nucleophilic cleavage with

Solid-phase syntheses of triazines (Table 15.32) include the cyclocondensation of polystyrene-bound isothiuronium salts with /V-(cyano)iminodithiocarbonates and the cyclization with simultaneous cleavage from the support of derivatives of a-amino acid hydrazides (Table 15.32). (Benzylthio)triazines, such as those listed in Table 15.32 (Entries 1 and 2), have been cleaved from a support by oxidation to sulfoxides or sul-fones with N-benzenesulfonyl-3-phenyloxaziridine, followed by nucleophilic cleavage with primary or secondary aliphatic amines or with electron-rich anilines (see Section 3.8). 

Commercially available 2-fluoro-5-nitroaniline was diazotized and coupled to benzylaminomethylpolystyrene to give the immobilized triazene. After nucleophilic displacement with primary amines to furnish an aniline resin, the cleavage with trifluoroacetic acid in dichloromethane proceeded smoothly at room temperature within minutes, resulting in nitrobenzotriazoles [627],... 

The A-acetyl derivatives of the 2-alkylthio-l,3-thiadiazol-4-imines (124, R = SR, R = Ac) undergo nucleophilic displacement reaction with amines (benzylamine, cyclohexylamine, morpholine, or aniline) giving the 2-amino derivatives (124, R = NRj, R = Ac). The salt (126, R = R = Ph, R = R = H, X = Cl) reacts with aniline at room temperature giving 4-anilino-2-phenyl-l,3-thiazole (128), presumably by a mechanism involving cleavage of the heterocyclic ring. ... 

Immobilized, highly reactive phenyl esters can be prepared by acylating resin-bound 4-acyl-2-nitrophenol (Entry 4, Table 3.13 [285-288]) or 4-(aminocarbonyl)-2,3,5,6-tetrafluorophenol (Entries 7 and 8, Table 3.13). These esters are similar to oxime esters (see Section 3.3.3.3), and even react with weak nucleophiles such as anilines or alcohols. This type of linker is not, therefore, well suited for long synthetic sequences on insoluble supports, but only for the preparation of simple acid derivatives. Because cleavage yields the unchanged phenol, these resins can be reused several times, which renders this strategy of preparing acid derivatives quite cost-effective. 

Monomolecular C-X bond cleavage energies are accessible by thermochemical cycle calculations such bond dissociation processes are often induced by nucleophiles, at least with X = SiR3 [163, 171]. As a consequence, rates are much faster than expected on the basis of thermochemical data. Detailed data are available for aniline radical cation desilylation [170]. 

The importance of bond cleavage in the TS is also found in the nucleophilic displacement of chloride in 4-Y-2,6-dinitrochlorobenzenes with substituted anilines (XC6H4NH2) in a series of MeOH-MeCN mixtures102. The / x values are large (= 0.97) and are practically constant regardless of the Y-substituent, N02, CN and CF3, and the reaction rate decreases as the MeCN content increases. 

The propensity for C-N vs. N-H activation correlates well with substituent Hammet parameters groups that increase the basicity of aniline increase the relative rate of N-H activation, suggesting that nucleophilic attack by the amine at an empty d /dy orbital of Ta(silox)3 preceeds oxidative addition. On the other hand, electron-withdrawing substituents decrease the rate of N-H activation and increase the rate of C-N activation, similarly to the effects observed on electrophilic aromatic substitution. Nucleophilic attack by the filled d a orbital of Ta(silox)3 is expected to occur at the arylamine ipso carbon preceding C-N oxidative addition. The carbon-heteroatom cleavages can be accomodated by mechanisms using both electrophilic and nucleophilic sites on the metal center. 

O-Demethylation has been observed as well as, or instead of, nucleophilic displacement on reaction of 3,4,5-chloro/methoxy pyridazines and 4,5-chloro/methoxy-2-methyl-3(2//)-py-ridazinones with morpholine (e.g.. Scheme 63). Demethylation was observed at all ring positions, but usually adjacent to chlorine or a carbonyl group, and A -methylmorpholine was isolated, consistent with demethylation rather than hydrolysis. The demethylation can also occur with other primary and secondary amines such as diethylamine, butylamine, and piperidine, but not with pyrrolidine and aniline <87H(26)1 >. 3-Phenolic ethers of pyridazines are resistant to reductive cleavage of the aryl ether bond under the conditions of phase transfer catalytic hydrogenolysis <82T3775>. 

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