Nucleophilic substitution of other groups

Halo-substituted 3-hydroxypyridazin-6(lFf)-ones react in some instances by cine substitution. For example, 4-chloro-l-methyl-2-phenylpyridazin-6(lFf)-one, when treated with piperidine, yields a mixture of the corresponding 4- and 5-piperidino isomers in nearly equal amounts. 

When an acetylamino group is attached at an ortho position the replacement of chlorine is followed by cyclization. For example, 4-acetylamino-5-chloro-l-phenylpyridazin-6(lH)-one is converted with hydrogen sulfide in DMF to 2-methyl-6-phenylthiazolo[4,5- f]pyridazin-7(6//)-one (116). 

When thiourea or thiosemicarbazide are used for substitution of a chlorine atom with a mercapto group, thiouronium salts are formed first, and they are hydrolysed by aqueous base. Other groups, such as alkoxy, alkyl, amino and cyano, if present, are usually not 

Phosphorus pentasulfide in pyridine can be used also for simultaneous substitution of oxygen and chlorine in polysubstituted pyridazinones. For example, 4,5-dichloro- and 

Alkylthio- and arylthio-pyridazines can be prepared from the corresponding halo-substituted pyridazines by using appropriate alkyl and aryl thiolates. 

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Similar nucleophilic substitutions of other groups during diazotizations (chloro-de-nitrations) were found by Oku and Matsui (1979) and Trimmer et al. (1985). 

Other modifications of acid wool dyes have groups which react by nucleophilic substitution of basic groups ia proteia fibers (NH2 groups, etc). The iatroduction of Procion dyes by ICI ia 1956 was the most important development ia the field of technological azo dye chemistry. Chemically, many of the reactive dyes are prepared from the group of the anionic monoazo dyes (see Dyes, reactive). 

Nucleophilic substitution with heteroaryl halides is a particularly useful and important reaction. Due to higher reactivity of heteroaryl halides (e.g. 35, equation 24) in nucleophilic substitution these reactions are widely employed for synthesis of Al-heteroaryl hydroxylamines such as 36. Nucleophilic substitution of halogen or sulfonate functions has been performed at positions 2 and 4 of pyridine , quinoline, pyrimidine , pyridazine, pyrazine, purine and 1,3,5-triazine systems. In highly activated positions nucleophilic substitutions of other than halogen functional groups such as amino or methoxy are also common. 

In comparison with conventional nucleophilic displacement of other groups, such as chlorine, bromine and iodine, fluorodenitration is much faster. Therefore, substitution can be carried out under milder reaction conditions. In particular, lower temperatures allow the synthesis of complex, thermolabile derivatives, e.g. [ F]spiroperidol from its inactive nitro analog using rubidium [ F]fluoride. ... 

Hydrolysis and polycondensation reactions usually occur simultaneously and the reaction rates depend on the type of precursor as well as on reaction conditions such as pH, temperature, and ionic strength [8]. Hydrolysis of alkoxy precursors (=M-OR , where M is the metal atom and R is the alkyl group) occurs by water due to electrophilic reaction in the presence of acid catalyst or by nucleophilic substitution of alkoxy groups in the presence of base catalyst [3,9]. The hydrolyzed precursors (=M-OH) can react either with alloy precursors (alcoxolation) or with other hydrolyzed precursors (oxolation). In both cases the mechanism is nucleophilic substitution or nucleophilic addition for which the result is polycondensation [3,10]. The reactions that describe the sol-gel process are as follows ... 

Nucleophilic substitution of pyridines is discussed in previous sections in relation to the following cyclic transition states (Section II, B, 5), hydrogen bonding and cationization (Section II, C), the leaving group (Section II, D,) and the effect of other substituents (Section II, E) and of the nucleophile (Section II, F). 

Nucleophilic substitution of as-triazines is discussed in relation to hydrogen bonding and the effects of the leaving group and of other nuclear substituents in Sections II,C,D, and E, respectively. 

To derive the maximum amount of information about intranuclear and intemuclear activation for nucleophilic substitution of bicyclo-aromatics, the kinetic studies on quinolines and isoquinolines are related herein to those on halo-1- and -2-nitro-naphthalenes, and data on polyazanaphthalenes are compared with those on poly-nitronaphthalenes. The reactivity rules thereby deduced are based on such limited data, however, that they should be regarded as tentative and subject to confirmation or modification on the basis of further experimental study. In many cases, only a single reaction has been investigated. From the data in Tables IX to XVI, one can derive certain conclusions about the effects of the nucleophile, leaving group, other substituents, solvent, and comparison temperature, all of which are summarized at the end of this section. 

The nucleophilic substitution of quinoline as affected by cationiza-tion and hydrogen bonding is discussed in Section II, C, by the leaving group and other substituents in Sections II, D and II, E, respectively, and in Section III, A, 2, and by the nucleophile in Section II, F. 

The effect of the leaving group and of other substituents on nucleophilic substitution of cinnolines is discussed in Sections II, D and II, E, respectively. 

In a classic study in 1940, Crossley and coworkers demonstrated that the rates of nucleophilic substitution of the diazonio group of the arenediazonium ion in acidic aqueous solution were independent of the nucleophile concentration, and that these rates were identical with the rate of hydrolysis. Since that time it has therefore been accepted without question that these reactions proceed by a DN + AN mechanism, i.e., that they consist of a rate-determining irreversible dissociation of the diazonium ion into an aryl cation and nitrogen followed by rapid reactions of the cation with water or other nucleophiles present in solution (Scheme 8-6). 

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