Solid nucleophilic reagents

Fig. 40 Microwave-assisted substitution of imidazole on C-2 in solid-phase. Reagents and conditions a benzaldehyde, N,N-diisopropylethylamine, CH2CI2, 24 h, rt b Nucleophile, TEA, Bp3Et20, THP, MW 120 °C, 5 min, closed vessel...

Weakly nucleophilic heterocyclic amines have efficiently been acylated utilizing solid-supported reagent 7 [13]. Here, the electron-deficient phenol group allows for intermediate anchoring of an acyl chloride onto the resin which then is released upon treatment with various 2-aminopyridines and 2-aminothiazoles. Traces of unreacted starting material were then conveniently removed by addition of the acidic ion exchange resin Amberlite IRA-120. 

Water, alcohols, and carboxylic acids are polar protic solvents able to form hydrogen bonds (hydroxylic solvents). They solvate both cations and anions well. A nucleophilic reagent such as bromide ion must be accompanied by a cation, say, the sodium ion, and hydroxylic solvents dissolve salts such as NaBr by hydrogen bonding to the anion and electron donation to the cation. This is solvation by a polar protic solvent. These solvents do not ionize the salt, which already exists in the solid state as ions they separate and solvate the ions already present. 

Aldehydes and ketones are characterized through the addition tortliVcafbony 1 group of nucleophilic reagents, especially derivatives of ammonia (Sec. 19.14). An aldehyde or ketone will, for example, react with 2,4-dinitrophenylhydrazine to form an insoluble yellow or red solid. 

Alkane-and arenesulfenyl chlorides add to alkenes and alkynes thus, the addition of 2,4-dinitrobezenesulfenyl chloride (61) may be used to prepare solid derivatives of alkenes, e.g. the adduct (62) (Scheme 37). The Markownikoff addition of a sulfenyl chloride to an alkene is stereospecifically trans the adduct may be sequentially treated with a Lewis acid and a nucleophilic reagent to achieve the introduction of a new carbon-carbon bond (64) via the episulfenium ion intermediate (63) (Scheme 38). The procedure can also be applied to the synthesis of unsaturated sulfides, e.g. (65) (Scheme 39). 

Kim, K. and Le, K. (1999) Two efficient A-acylation methods mediated by solid-supported reagents for weakly nucleophilic heterocyclic amines. Synlett, 1957-1959. 

Consider the reaction between an organic substrate RX and a nucleophilic reagent MY present in an immiscible aqueous solution or an insoluble solid phase. The addition of a quaternary ammonium salt, traditionally represented as QX, leads to the following reactions ... 

Usually, the nucleophilic substitutions under NPTC condition are described by an S -type reaction both in solid-liquid and liquid-liquid systems in which they can proceed at the interface through the formation of cyclic adsorption complexes. The activity of the nucleophilic reagent in the organic phase is determined by the polarity of the organic solution and the hydration in liquid-liquid system. In the solid-liquid system, the reaction is highly affected by the organic solvent. 

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