CHE 230

1. Identify the electrophilic C atom and the leaving group.
   • The electrophilic C atom is always sp³-hybridized in the substitution reactions with which we are concerned.
   • The leaving group is often Cl, Br, I, or a sulfonate such as OTs or OMs.
   • Under acidic conditions, the leaving group may be an OH group, especially if it is part of a tertiary alcohol.
   • Under basic conditions, the OH group is a leaving group only if it is first converted to a better leaving group, often with the reagents TsCl and MsCl (RSO₂Cl).
   • Occasionally the leaving group is a positively charged group that can break off to make a small, neutral molecule such as N₂, SMe₂, NMe₃, or OMe₂.
   • The reagents SOCl₂ and PBr₃ are used to convert an OH group into a Cl or Br group, respectively.

2. Identify the nucleophilic atom.
   • An atom that is attached to a metal is likely to be the nucleophilic atom.
   • If no metal is present, a negatively charged atom that bears a lone pair may is likely to be the nucleophilic atom.
   • If no negatively charged atom is present, a neutral atom that bears an acidic H atom may be the nucleophilic atom, especially if it is the solvent or the conditions are basic. (E.g., NH₃, HBr, HCl, H₂O, EtOH, RSH, RCO₂H such as AcOH, RC≡CH, and a C atom adjacent to a C=O group.)
   • If no electronegative atom bearing an acidic H atom is present, a neutral atom that bears a lone pair may be the nucleophilic atom. (E.g., Ph₃P, Me₂S, Et₃N.)
   • A species that is present in only catalytic amounts cannot contain the nucleophilic atom.

3. Erase the bond between the electrophilic C atom and the leaving group, and create a new bond between the electrophilic C atom and the nucleophilic atom.
   • If the nucleophilic atom bears a metal, the bond between the nucleophilic atom and the metal is also cleaved in the product, and the nucleophilic atom remains uncharged.
   • If the nucleophilic atom is negatively charged, it is neutral in the product.
   • If the nucleophilic atom bears an acidic H atom, the bond between the nucleophilic atom and the H atom is also cleaved in the product, and the nucleophilic atom remains uncharged.
   • If the nucleophilic atom is a neutral, lone-pair-bearing atom that does not have an acidic H atom, it is positively charged in the product.
   • The electrophilic C atom's formal charge remains unchanged. The leaving group decreases its formal charge by one.
   • It is customary to draw only the product that contains the original electrophilic C atom.

4. If the electrophilic C atom was stereogenic and its configuration was shown (bold or hashed bond), the stereochemistry of the product must be assigned.
   • If the reaction conditions are acidic (S_N1 mechanism), then the electrophilic C atom's configuration becomes scrambled in the product (squiggly bond).
   • If the reaction conditions are basic (S_N2 mechanism), then the electrophilic C atom's configuration becomes inverted in the product (bold to hashed or vice versa). If the nucleophile and the leaving group are assigned the same priority with respect to the other substituents on the electrophilic C atom, the configuration will change from R to S or vice versa.

Drawing an elimination product:

1. Identify the electrophilic C atom and the leaving group.
   • Under acidic conditions:
     • The electrophilic C atom is always sp³-hybridized.
     • The leaving group is often Cl, Br, I, OTs, OMs, OH, or OR (R = Me, Et, or COCH₃).
   • Under neutral conditions:
     • The electrophilic C atom is always sp³-hybridized.
     • The leaving group is often Cl, Br, or I. The OH group is usually a leaving group only if it is first converted to a better leaving group, often with the reagents TsCl and MsCl (RSO₂Cl).
   • Under basic conditions:
     • The electrophilic C atom is usually sp³-hybridized, but it may be sp²-hybridized.
     • The leaving group is often Cl, Br, or I. The OH group is usually a leaving group only if it is first converted to a better leaving group, often with the reagents TsCl and MsCl (RSO₂Cl).
   • Occasionally the leaving group is a positively charged group that can break off to make a small, neutral molecule such as N₂, SMe₂, NMe₃, or OMe₂.

2. Draw in the H atoms on the electrophilic C atom and on all C atoms attached to it (Grossman's rule).

3. Erase the bond between the electrophilic C atom and the leaving group, erase the bond between a H atom and a C atom adjacent to the electrophilic C atom, and create a new π bond between the two aforementioned C atoms.
   • If there is more than one kind of C atom adjacent to the electrophilic C atom, the H is usually removed from the adjacent C atom that is most substituted (Zaitsev's rule).
   • If the product has E-Z isomers, the lower energy isomer is usually produced (Zaitsev's rule).
   • Under basic conditions only, when both the electrophilic C atom and the C atom from which the H is removed are stereogenic, Zaitsev's rule may be superseded by the requirement for antiperiplanar elimination. The lowest energy product that can be obtained from an anti disposition of the C-X and C-H bonds that break is obtained.
   • It is customary to draw only the product that contains the original electrophilic C atom.