Nucleophilic Substitution: Nucleophiles in SN2 and SN1 reactions

Any species that has an unshared pair of electrons (any Lewis base) can act as a nucleophile whether it is neutral or has a negative charge.

A nucleophile (Nu:^-) is a species that attacks an electrophile (E⁺) (electron pair acceptor) by making a pair of electrons available to it; it is an electron pair donor:

Nu:^-    +     E⁺        →       Nu-E    +     by-products

S_N2 reactions and nucleophiles

The rates of S_N2 reactions are dependent of the identity of the nucleophile since it does appear in the rate determining step:

R =  [Nu:^- ] * [E⁺]

This may be illustrated by the effect of changing the nucleophile from H₂O to OH^- for CH₃Br which reacts by an S_N2 mechanism (Fig. 1). The rate of reaction is multiplied by 5000:

Fig. 1: Effect of changing the nucleophile from H₂O to OH^- in the S_N2 reaction of CH₃Br. The reaction rate is multiplied by approximately 5000 (R₂  ≈ 5000 * R₁). The OH^-  is a more powerful nucleophile than H₂O.

Which nucleophiles are considered “good nucleophiles”?

Good and poor nucleophiles or high and low nucleophilicity are kinetically determined concepts. Answers to these questions are obtained experimentally via pairs of S_N reactions which are carried out as competition experiments. In a competition experiment two nucleophiles react simultaneously with one substrate and two reaction products are produced. The main product is the compound that results from the more reactive nucleophile.

For S_N2 reactions in solution, there are four main principles that govern the effect of the nucleophile on the rate although the nucleophilicity order is not absolute but depends on other factors such as on substrate, leaving group and solvent.  
A nucleophile with a negative charge is always a more powerful nucleophile than its conjugate acid (i.e. OH^- more powerful than H₂O, NH₂^- more powerful than NH₃).

Nucleophilicity follows the order of basicity when comparing nucleophiles whose attacking atom is in the same row of the periodic table. An approximate order of nucleophilicity  is as follows:

NH₂^- > RO^- > OH^- > R₂NH > ArO^- > NH₃ > pyridine > F^- > H₂O > ClO₄^-

Nucleophilicity increases going down the periodic table:

I^-> Br^- > Cl^- > F^- (this order is solvent dependent)

RS^- > RO^-

RSH > ROH

The main reason that smaller halides (nucleophiles in general)  are less powerful nucleophiles than the larger ones is because they are solvated more effectively by the usual protic solvents (Fig.2). That is, because the negative charge in F^- is more concentrated than the charge of I^-, the former is more tightly surrounded by a shell of solvent molecules that become a barrier between it and the substrate (electrophile).

Fig. 2: The smaller negatively charged F^- is more effectively solvated -because of H-bonding - in polar solvents than the larger I- and as a result becomes a weaker nucleophile. In an aprotic solvent like DMF – where H bonding does not exist-  the above order of nucleophilicity is reversed.