Nucleophilic substitution—continued

TABLE 8.1 Functional Group Transformation via Nucleophilic Substitution [Continued)... 

How deeply one wishes to query the mechanism depends on the detail sought. In one sense, the quest is never done a finer and finer resolution of the mechanism may be obtained with further study. For example, the rates and mechanisms of electron transfer reactions have been studied experimentally and theoretically since the 1950s. but the research continues unabated as issues of ever finer detail and broader import are examined. The same can be said of other reactions—nucleophilic substitution, hydrolysis, etc. 

Additions to quinoline derivatives also continued to be reported last year. Chiral dihydroquinoline-2-nitriles 55 were prepared in up to 91% ee via a catalytic, asymmetric Reissert-type reaction promoted by a Lewis acid-Lewis base bifunctional catalyst. The dihydroquinoline-2-nitrile derivatives can be converted to tetrahydroquinoline-2-carboxylates without any loss of enantiomeric purity <00JA6327>. In addition the cyanomethyl group was introduced selectively at the C2-position of quinoline derivatives by reaction of trimethylsilylacetonitrile with quinolinium methiodides in the presence of CsF <00JOC907>. The reaction of quinolylmethyl and l-(quinolyl)ethylacetates with dimethylmalonate anion in the presence of Pd(0) was reported. Products of nucleophilic substitution and elimination and reduction products were obtained . Pyridoquinolines were prepared in one step from quinolines and 6-substituted quinolines under Friedel-Crafts conditions <00JCS(P1)2898>. 

Chemical modification of polymers (J.) still remains a field of continuously increasing importance in macromolecular chemistry. In spite of its high diversification, it may be divided into 2 distinct but complementary main research lines a) the fundamental study of the chemical reactivity of macromolecular chains b) the synthesis of new homopolymers and copolymers, and the functionalization of linear or crosslinked polymers. Some of these facets have been reviewed in the last years (2-6), and the purpose of this presentation is to illustrate a number of characteristic topics both from fundamental and applied points of view, through some literature data and through our own studies on nucleophilic substitution of polymethylmethacrylate (PMMA). 

The fonnation of these substances contradicts common ideas on nucleophilic substitution. The presence of radical traps (oxygen or tetrabromobenzoquinone) decelerates the formation of both unexpected compounds and product of thioarylation. Consequently, the first stage of the reaction depicted in Scheme 4.5 produces phenylthiyl radical and anion-radical of the substrate. Both electron-transfer products undergo further conversions The phenylthiyl radical gives diphenyldi-sulfide, and the anion-radical of the substrate produces 9-fluorenyl radical. The latter reacts in two directions—dimerizing, it forms bifluorenyl reacting with the nucleophile, it gives the anion-radical of the substitution product. The chain continues because the electron from the anion-radical is transferred to the unreacted molecule of the substrate. The latter loses bromine and then reacts with the nucleophile, and so on (Scheme 4.6). 

A direct aza-Wittig cyclization to triazolotriazine 176 (Scheme 67) takes place when triazinone 174 is treated with diphenylthiourea, the latter being substituted on the nitrogen. Elimination of triphenylphosphane sulfide from 175 makes 1,2,4-triazole accessible [86JCS(P1)2037]. When the nucleophilic attack continues on the sulfur, thiadiazoles are formed [86JCS(P1)2037]. 

Typical phase transfer catalysis in liquid-liquid systems combines processes in which Na+ or K+ salts of inorganic and organic anions derived from strong adds (phenolates, thiolates, carboxylates, etc.) are continuously transferred from aqueous (often alkaline) solutions to the organic phase by the phase transfer catalysts. Applications include nucleophilic substitution, addition, elimination, oxidation, and reduction reactions. 

Overall, Eqs. (l)-(3) depict a nucleophilic substitution Eq. (4) in which radicals and radical anions are intermediates. Once the radical anion of the substrate is formed it fragments into a radical and the anion of the leaving group (Eq. (1)). The aryl radical can react with the nucleophile to furnish a radical anion (Eq. (2)), which by ET to the substrate forms the intermediates needed to continue the propagation cycle (Eq. (3)). The mechanism has termination steps that depend on the substrate, the nucleophile and experimental conditions. Not many initiation events are needed, but in this case, the propagation cycle must be fast and efficient to allow for long chains to build up. 

An Sjuyl-type (S l ) mechanism has been proposed in the synthesis of poly(2,6-dimethyl-l,4-phenylene ether) through the anion-radical polymerization of 4-bromo-2,6-dimethylphenoxide ions (204) under phase-transfer catalysed conditions269. Ions 204 are oxidized to give an oxygen radical 205. The propagation consists of the radical nucleophilic substitution by 205 at the ipso position of the bromine in 204 (equation 144). The anion-radical 206 thus formed eliminates a bromide ion to form a dimer phenoxy radical 207 (equation 145). A polymeric phenoxy radical results by continuation of this radical nucleophilic substitution. 

Continuing previous isotopic studies related to synthesis and PET applications of dopamine antagonists YM-09151-2 (312a, 312b)304, the NCA[18F]-labelled analogues of YM-09151-2 (313 and 314) have been synthesized305 by the nucleophilic substitutions of Af-methanesulphonoxyalkyl derivatives of nor-YM-09151-2 with [18F] (equation 133). 

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