Neucleophile As electron pair donors, nucleophiles musteither contain an electron pair that is easilyavailable because it is nonbonding or theymust contain a bonding electron pair thatcan be donated from the bond involved andthus be made available to the reactionpartner. From this it follows that nucleophiles areusually anions or neutral species but notcations.
Good and Poor Nucleophiles Within a group of nucleophiles thatattack at the electrophile with the sameatom, the nucleophilicity decreases withdecreasing basicity of the nucleophile Nucleophilicity is a measure of howreadily a compound (a nucleophile) isable to attack an electron-deficient atom.
Nucleophilicity of O nucleophileswith different basicities.
Nucleophilicity of N and O nucleophilesthat are sterically hindered to differentdegrees.
Nucleophilicity decreases withincreasing electronegativity of theattacking atom.In comparisons of atomic centersfrom the same group of the periodictable.
The nucleophilicity of a given nucleophilic center isincreased by attached heteroatoms that possessfree electron pairs (-effect)
Nucleophilic AliphaticsubstitutionTo ensure that reaction occurs in homogeneous solution, solvents arechosen that dissolve both the alkyl halide and the ionic salt. The alkylhalide substrates are soluble in organic solvents, but the salts often arenot. Inorganic salts are soluble in water, but alkyl halides are not. Mixedsolvents such as ethanol–water mixtures that can dissolve enough ofboth the substrate and the nucleophile to give fairly concentratedsolutions are frequently used. Many salts, as well as most alkyl halides,possess significant solubility in dimethyl sulfoxide (DMSO), which makesthis a good medium for carrying out nucleophilic substitution reactions.
Type of Nucleophilic Aliphaticsubstitution Reaction
The SN2 Mechanism a single step process Involves no intermediates Involves only one transition state, which is oflow polarity Follows second order (bimolecular) kinetics.That is, rate=k[substrate][nucleophile] backside attack
The Effect of the Solvent In a protic solvent, is the smallest atom the poorestnucleophile even though it is the strongest base. Protic solvents are hydrogen bond donors. The interaction between the ion and the dipole of theprotic solvent is called an ion–dipole interaction. Because the solvent shields the nucleophile, at leastone of the ion–dipole interactions must be brokenbefore the nucleophile can participate in a SN2reaction. Weak bases interact weakly with proticsolvents, whereas strong bases interact morestrongly because they are better at sharing theirelectrons.
AN ENZYME-CATALYZEDNUCLEOPHILIC SUBSTITUTIONOF AN ALKYL HALIDE Enzymes that catalyze these reactions areknown as haloalkane dehalogenases. The haloalkane dehydrogenase is believed toact by using one of its side-chain carboxylatesto displace chloride by an SN2 mechanism
THE SN1 NUCLEOPHILICSUBSTITUTION Hughes and Ingold observed that thehydrolysis of tert-butyl bromide, whichoccurs readily, is characterized by afirst-order rate law:
Experimental Evidence 1. The rate law shows that the rate of the reactiondepends only on the concentration of the alkyl halide. Thismeans that we must be observing a reaction whose rate-determining step involves only the alkyl halide. 2. When the methyl groups of tert-butyl bromide aresuccessively replaced by hydrogens, the rate of theSN1reaction decreases progressively . This is opposite tothe order of reactivity exhibited by alkyl halides in SN2reactions. 3. The reaction of an alkyl halide in which the halogen isbonded to an asymmetric carbon forms twostereoisomers: one with the same relative configuration atthe asymmetric carbon as the reacting alkyl halide, theother with the inverted configuration.
Factors Affecting SN1 Reactions The Leaving Group The Solvent Carbocation Rearrangements
The Leaving Group two factors affect the rate of an reaction: the ease with which the leaving groupdissociates from the carbon the stability of the carbocation that is formed. The weaker the base, the less tightly it isbonded to the carbon and the easier it is tobreak the carbon–halogen bond. As a result, an alkyl iodide is the mostreactive and an alkyl fluoride is the leastreactive of the alkyl halides
The Solvent The major effect of the solvent is on the rate ofnucleophilic substitution, not on what theproducts are. The higher the dielectric constant of solvent(polar) , the better the medium is able tosupport separated positively and negativelycharged species. The rate of solvolysis of tert-butyl chlorideincreases dramatically as the dielectricconstant of the solvent increases. Aprotic solvents, lack OH groups and do notsolvate anions very strongly, leaving themmuch more able to express their nucleophiliccharacter.