At that stage we said that nucleophilicity towards the carbonyl group parallels basicity almost exactly. We are able to use pKa as a guide to the effectiveness of nucleophilic substitution reactions at the carbonyl group. During this chapter you have had various hints that nucleophilicity towards saturated car bon is not so straightforward. Now we must look at this question seriously and try to give you helpful guidelines.

 1. If the atom that is forming the new bond to carbon is the same over a range of nucleophiles—it might be oxygen, for example, and the nucleophiles might be HO⁻, PhO⁻, AcO⁻, and TsO⁻—then nucleophilicity does parallel basicity. The anions of the weakest acids are the best nucleophiles. The order for the nucleophiles we have just mentioned will be: HO⁻ > PhO⁻ > AcO⁻ > TsO⁻. The actual values for the rates of attack of the various nucleophiles on MeBr in EtOH relative to the rate of reaction with water (= 1) are given in the table below.

2. If the atoms that are forming the new bond to carbon are not the same over the range of nucleophiles we are considering, then another factor is important. In the very last examples, we have been discussing we have emphasized that RS− is an excellent nucleophile for saturated carbon. Let us put that another way: RS− is a better nucleophile for saturated carbon than RO−, even though RO− is more basic than RS− (see table below).

Sulfur is plainly a better nucleophile than oxygen for saturated carbon. Why should this be? As we discussed back in Chapter 5, there are two main factors controlling bimolecular reactions: (1) electrostatic attraction (simple attraction of opposite charges or partial charges) and (2) bonding interactions between the HOMO of the nucleophile and the LUMO of the electrophile.

A proton is, of course, positively charged, so electrostatic attraction is the more important factor in nucleophilicity towards H+, or pKa. The carbonyl group too has a substantial positive charge on the carbon atom, arising from the uneven distribution of electrons in the C=O π bond, and reactions of nucleophiles with carbonyl groups are also heavily influenced by electrostatic attraction, with HOMO–LUMO interactions playing a smaller role. When it comes to saturated carbon atoms carrying leaving groups, polarization is typically much less important. There is, of course, some polarity in the bond between a saturated car bon atom and, say, a bromine atom, but the electronegativity difference between C and Br is less than half that between C and O. In alkyl iodides, one of the best classes of electrophiles in SN2 reactions, there is in fact almost no dipole at all—the electronegativity of C is 2.55 and that of I is 2.66.

● Electrostatic attraction is often unimportant in SN2 reactions.

What does matter is the strength of the HOMO–LUMO interaction. In a nucleophilic attack on the carbonyl group, the nucleophile adds in to the low-energy π* orbital. In a nucleophilic attack on a saturated carbon atom, the nucleophile must donate its electrons to the σ* orbital of the C–X bond, as illustrated in the margin for an alkyl bromide reacting with the non bonding lone pair of a nucleophile. σ* antibonding orbitals are, of course, higher in energy than non-bonding lone pairs, but the higher the energy of the nucleophile’s lone pair, the better the overlap. The 3sp3 lone-pair electrons of sulfur overlap better with the high-energy σ* orbital of the C–X bond than do the lower energy 2sp3 lone-pair electrons on oxygen because the higher energy of the sulfur electrons brings them closer in energy to the C–X σ* orbital. The conclusion is that nucleophiles from lower down the periodic table are more effective in SN2 reactions than those from the top rows.

● Typically, nucleophilic power towards saturated carbon goes like this:

I⁻ > Br⁻ > Cl⁻ > F⁻

RSe⁻ > RS⁻ > RO⁻

 R3P: > R3N:

مواضيع ذات صلة

The Mannich reaction

Base-promoted halogenation

Halogenation

Racemization

Thermodynamically stable enols: 1,3-dicarbonyl compounds

Kinetically stable enols

Summary of types of enol and enolate

The intermediate in the base-catalysed reaction is an enolate ion

Enolization is catalysed by acids and bases

Evidence for the equilibration of carbonyl compounds with enols

Tautomerism: formation of enols by proton transfer

Hydration of alkynes