Nucleophiles lone-pair

A nucleophile is a compound that has a relatively high energy pair of electrons available to make a new bond. A nucleophilic atom may be neutral or negatively charged. There are three classes of nucleophiles lone-pair nucleophiles, cr-bond nucleophiles, and rr-bond nucleophiles. 

The division of nucleophiles into three types is completely artificial. Nature does not stop to consider whether a nucleophile is a 7r-bond nucleophile or a lone-pair nucleophile before a reaction proceeds. The distinctions are intended only to train you to spot nucleophilic atoms or functional groups with ease. 

Lone-pair nucleophiles contain atoms with lone pairs. The lone pair is used to make anew bond to an electrophilic atom. Alcohols (ROH), alkoxides (RO ), amines (R3N), metal amides (R2N ), halides (X ), thiols (RSH), sulfides (R2S), and phosphines (R3P) are all examples of lone-pair nucleophiles, as are the O atoms of car-... 

The very polarized bond between a metal and a nonmetal, E-M, is often thought of as being like an ionic bond (E M+) thus, PhC=C-Li, H3C-MgBr, and EiAII I3 are sometimes drawn as PhC=C , H3C , and H , respectively. By this analogy, cr-bond nucleophiles are actually lone-pair nucleophiles. 

Lone-pair nucleophiles that are good bases (RO, RC=C, RS, R2N ) can exist under basic conditions only, but weakly basic lone-pair nucleophiles (halides, RCO2, RSO3, R2S, R3P) can exist under either acidic or basic conditions. Water and alcohols can exist under either basic or acidic conditions, but under basic conditions they are deprotonated before they react with an electrophile, whereas under acidic conditions they are not. Under acidic conditions, amines (R3N) exist as their ammonium salts, which lack any lone pairs, and so they must be deprotonated in an unfavorable equilibrium process before they can act as nucleophiles. 

Lone-pair nucleophiles are by far the most enthusiastic participants in Sn2 substitution reactions. Sigma-bond nucleophiles may also participate in Sn2 reactions, but they do not do so as often as lone-pair nucleophiles. By contrast, 7r-bond nucleophiles do not usually have sufficiently high energy to react with an atom that already has an octet. The major exceptions to this rule are the enam-ines (R2N-CR=CR2 <—> R2N=CR-CR2), which are sufficiently nucleophilic at the j8 position to attack particularly reactive alkyl halides such as CH3I and al-lylic and benzylic bromides, and enolates (0-CR=CR2 <—> 0=CR-CR2), which react with many alkyl halides. 

Common error alert A lone-pair nucleophile bearing a proton (H20, ROH, RC02H, RNH2, etc.), is always deprotonated immediately after it adds to the car-bocation. The two steps combined—addition, then deprotonation—are the microscopic reverse of the ionization of a carbon-heteroatom bond under acidic conditions. When the nucleophile is RC02H, the carbonyl O makes the new bond, not the O of the OH group. 

Nonbonding electron pairs are good electron sources, especially lone pairs of anions. The following list gives the relative nucleophilicity of many lone pair nucleophiles in an Sn2 reaction on methyl iodide. An anion is always a better nucleophile than its neutral counterpart methoxide is almost 2 million times more nucleophilic than methanol. 

The release of the shortened fatty acid from the enzyme is an example of a lone pair nucleophile attacking a L-C=0 sink as in Section 8.8.1. Again, a general base catalyzes the addition to the thioester. 

A pAa chart can be used as a reference for nucleophilicity only if the difference in softness is considered. A partially plus carbon atom is a much softer electrophile than a proton. Soft ions are more nucleophilic in protic solvents because tighter solvation greatly decreases the nucleophilicity of the hard ions. Also, steric hindrance decreases nucleophilicity. To rank lone pair nucleophilicity in protic solvents with soft... 

The raised energy of the HOMO also provides an explanation with an SET mechanism, since it allows an electron to be transferred more easily to the LUMO of the electrophile, and the radical pair then couple, as usual. A single electron removed from one of the two pairs will leave behind a stabilised radical, and so the rate constant of a reaction of an a-effect nucleophile ought to be more sensitive to the ionisation potential (LUMO energy) of the electrophile than the rate constant with a normal lone-pair nucleophile.277 This proved to be the case in the rates of N-methylation of a series of N-phenylhydroxylamines compared with the rates in some comparable anilines.278 Further support for an SET mechanism is provided by superoxide anions, RO2 , which are exceptionally powerful nucleophiles benefiting simultaneously from an a-effect and from the availability of an unpaired electron.279... 

---