Alkyl hahde polarity

Hydroxyl Group. Reactions of the phenohc hydroxyl group iaclude the formation of salts, esters, and ethers. The sodium salt of the hydroxyl group is alkylated readily by an alkyl hahde (WiUiamson ether synthesis). Normally, only alkylation of the hydroxyl is observed. However, phenolate ions are ambident nucleophiles and under certain conditions, ring alkylation can also occur. Proper choice of reaction conditions can produce essentially exclusive substitution. Polar solvents favor formation of the ether nonpolar solvents favor ring substitution. 

To summarize, the amount of O-alkylation is maximized by use of an alkyl sulfate or alkyl sulfonate in a polar aprotic solvent. The amount of C-alkylation is maximized by use of an alkyl hahde in a less polar or protic solvent. The majority of synthetic operations involving ketone enolates are carried out in THF or DME using an alkyl bromide or alkyl iodide, and C-alkylation is favored. 

The large rate enhancements observed for bimolecnlar nncleophilic snbstitutions in polar aprotic solvents are nsed to advantage in synthetic apphcations. An example can be seen in the preparation of alkyl cyanides (nitriles) by the reaction of sodinm cyanide with alkyl hahdes ... 

Use of a polar protic solvent will greatly increase the rate of carbocation formation of an alkyl hahde in any Sj l reaction because of its ability to solvate cations and anions so effectively. 

Solvent effect (Sections 6.13C and 6.13D) An effect on relative rates of reaction caused by the solvent. For example, the use of a polar solvent will increase the rate of reaction of an alkyl hahde in an SnI reaction. 

The bond polarities of aryl-halogen and aryl-oxygen bonds compared to those in alkyl hahdes and alcohols provide a measure of the effect of the sp hybrid orbital on the O bond and of the resonance interactions between the nonbonded electrons of the substituent and the aromatic ring. The dipole moment of chlorobenzene is smaller than the dipole moment of chlorocyclohexane. 

After many years of investigation of the photochemistry of alkyl hahdes RX (X = Cl, Br, it was found that the photochemical reaction of alkyl iodides in nonpolar solvent leads to radical products in polar solvent, to carbocationic products (Scheme 1). Photoinduced alcoholysis and photodehalogenation of a-halo ketones (X = Cl, Br) in alcohols have been investigated by Tomioka et al. In their interesting work on photosolvolysis of a-halo ketones, they proposed that the homolysis of CX bonds produces a... 

N-Alkylpyrroles may be obtained by the Knorr synthesis or by the reaction of the pyrrolyl metallates, ie, Na, K, and Tl, with alkyl haUdes such as iodomethane, eg, 1-methylpyrrole [96-54-8]. Alkylation of pyrroles at the other ring positions can be carried out under mild conditions with allyhc or hensylic hahdes or under more stringent conditions (100—150°C) with CH I. However, unless most of the other ring positions are blocked, poly alkylation and polymerisation tend to occur. N-Alkylation of pyrroles is favored by polar solvents and weakly coordinating cations (Na", K" ). More strongly coordinating cations (Li", Mg " ) lead to more C-alkylation. 

It certainly demands quite extreme conditions, under which sodium hahdes, or still better, lithium halides or cyanides in a highly polar nonprotic medium such as DMSO or phospholine oxide [214,215,908,909] cleave the ester 130 under formation of alkyl halides. Alternatively, it succeeds in the presence of tertiary amines [910], in quinoline [911] or just in water in the presence of copper salts [912]. On the other hand boiling with 25% sulfuric acid [913] accomplished the same. 

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