Nucleophile Anionic Nucleophiles Anionic Nucleophiles Neutral Nucleophiles – – – – – – ( Weak Bases: I , Br , SCN , N3 , ( Strong Bases: HO , RO ) ( H2O, ROH, RSH, R3N ) – – – Alkyl Group CH3CO2 , RS , CN etc. )

pKa's > 15 pKa's ranging from -2 to 11 pKa's from -9 to 10 (left to right)

Rapid SN2 substitution. The rate may be reduced by Rapid SN2 substitution. E2 elimination may also SN2 substitution. (N ≈ S >>O) Primary substitution of β-carbons, as in the case of neopentyl. occur. e.g. RCH2– ClCH2CH2Cl + KOH ——> CH2=CHCl

SN2 substitution and / or E2 elimination (depending on E2 elimination will dominate. SN2 substitution. (N ≈ S >>O) Secondary the basicity of the nucleophile). Bases weaker than In high dielectric ionizing solvents, such as water, R2CH– acetate (pKa = 4.8) give less elimination. The rate of dimethyl sulfoxide & acetonitrile, SN1 and E1 substitution may be reduced by branching at the β- products may be formed slowly. carbons, and this will increase elimination.

E2 elimination will dominate with most nucleophiles E2 elimination will dominate. No SN2 substitution E2 elimination with nitrogen nucleophiles (they are Tertiary (even if they are weak bases). No SN2 substitution due will occur. In high dielectric ionizing solvents SN1 bases). No SN2 substitution. In high dielectric R3C– to steric hindrance. In high dielectric ionizing solvents, and E1 products may be formed. ionizing solvents SN1 and E1 products may be such as water, dimethyl sulfoxide & acetonitrile, SN1 formed. and E1 products may be expected.

Rapid SN2 substitution for 1º and 2º-halides. For 3º- Rapid SN2 substitution for 1º halides (note there are Nitrogen and sulfur nucleophiles will give SN2 Allyl halides a very slow SN2 substitution or, if the no β hydrogens). E2 elimination will compete with substitution in the case of 1º and 2º-halides. 3º- H2C=CHCH2– nucleophile is moderately basic, E2 elimination. In high substitution in 2º-halides, and dominate in the case halides will probably give E2 elimination with dielectric ionizing solvents, such as water, dimethyl of 3º-halides. In high dielectric ionizing solvents nitrogen nucleophiles (they are bases). In high sulfoxide & acetonitrile, SN1 and E1 products may be SN1 and E1 products may be formed. dielectric ionizing solvents SN1 and E1 products observed. may be formed. Water hydrolysis will be favorable for 2º & 3º-halides.

Rapid SN2 substitution for 1º and 2º-halides. For 3º- Rapid SN2 substitution for 1º halides (note there are Nitrogen and sulfur nucleophiles will give SN2 Benzyl halides a very slow SN2 substitution or, if the no β hydrogens. E2 elimination will compete with substitution in the case of 1º and 2º-halides. 3º- C6H5CH2– nucleophile is moderately basic, E2 elimination. In high substitution in 2º-halides, and dominate in the case halides will probably give E2 elimination with dielectric ionizing solvents, such as water, dimethyl of 3º-halides. In high dielectric ionizing solvents nitrogen nucleophiles (they are bases). In high sulfoxide & acetonitrile, SN1 and E1 products may be SN1 and E1 products may be formed. dielectric ionizing solvents SN1 and E1 products observed. may be formed. Water hydrolysis will be favorable for 2º & 3º-halides. Table taken from http://www.cem.msu.edu/~reusch/VirtualText/alhalrx3.htm#hal6