leaving group

Examples of leaving group in the following topics:

• Elimination

  • Elimination is a type of organic reaction in which a leaving group and vicinal hydrogen are removed, leaving behind a double bond.
  • In unimolecular elimination (E1), a leaving group first detaches itself from a carbon atom, leaving behind a carbocation.
  • In bimolecular elimination (E2), a base deprotonates a carbon vicinal to a leaving group, and the electrons from the C-H bond form a double bond with the adjacent carbon, displacing the leaving group.
  • As in SN2, the leaving group (LG) is "pushed" away by electrons that access the C-LG antibonding orbital.
  • In the case of E2, at the time of deprotonation the hydrogen must be antiperiplanar to the leaving group.

• Nucleophilic Substitution

  • Typically, strength of a leaving group's conjugate acid correlates with its lability.
  • In SN1 reactions, the rate-determining step is the removal of the leaving group.
  • Leaving groups are almost always negative.
  • In SN2, the nucleophile "pushes" the leaving group off the carbon in the R group.
  • Leaving groups for SN2 reactions can be similar to those used in SN1.

• Substitution and Elimination Reactions of Amines

  • Amine functions seldom serve as leaving groups in nucleophilic substitution or base-catalyzed elimination reactions.
  • In the case of alcohols and ethers, a useful technique for enhancing the reactivity of the oxygen function was to modify the leaving group (OH(–) or OR(–)) to improve its stability as an anion (or equivalent).
  • As noted earlier, 1º and 2º-amines are much weaker acids than alcohols, so it is not surprising that it is difficult to force the nitrogen function to assume the role of a nucleophilic leaving group.
  • In this context we note that the acidity of the putative ammonium leaving group is at least ten powers of ten less than that of an analogous oxonium species.
  • The favored anti orientation of the leaving group and beta-hydrogen, noted for dehydrohalogenation, is found for many Hofmann eliminations; but syn-elimination is also common, possibly because the attraction of opposite charges orients the hydroxide base near the 4º-ammonium leaving group.

• Elimination Reactions

  • The use of thionoesters, such as a xanthates, as radical generating functions was described above, and these groups may also serve as excellent radical leaving groups.
  • Once again, the tolerance of radical reactions for a variety of functional groups is demonstrated.

• Rearrangements of Cationic Oxygen

  • Removal of hydroxide anion from a hydroperoxide is energetically unfavorable, unless it is initially converted to a better leaving group in a manner similar to that used to facilitate substitution reactions of alcohols.
  • By protonating the hydroxyl group, the leaving group becomes water, thus generating an oxacation.
  • The migratory aptitude of various substituent groups (e.g. 1R & 2R) is generally: 3º-alkyl > 2º-alkyl ~ benzyl ~ phenyl > 1º-alkyl > methyl.
  • Stereoelectronic factors favor an anti-periplanar orientation of the migrating group to the leaving moiety, and will control the rearrangement in some cases.
  • In example #3 it is interesting that migration of the bridgehead 3º-alkyl group is preferred over a possible phenyl shift.

• Alcohols

  • Alcohols are functional groups characterized by the presence of an -OH group.
  • Alcohols are organic compounds in which the hydroxyl functional group (-OH) is bound to a carbon atom.
  • The presence of the -OH groups allows for hydrogen bonding with other -OH groups, hydrogen atoms, and other molecules.
  • Hydroxyl groups alone are not considered good leaving groups.
  • Often, their participation in nucleophilic substitution reactions is instigated by the protonation of the oxygen atom, leading to the formation a water moiety—a better leaving group.

• Acid-Base Catalysis

  • The factors that influence such differences in reactivity may be complex, but in the above cases are largely due to a poor anionic leaving group (eq. 4); aromatic stabilization and reduced nucleophilicity of a conjugated π-electron system (eq. 5); and reduced electrophilic character of a substituted carbonyl group (eq. 6).
  • The key factor here is the stability of the leaving anion (chloride vs. hydroxide).
  • Thus, chloride anion is much more stable and less reactive than is hydroxide anion, so the former is a better and more common leaving group.
  • We know that the carbon atom of a carbonyl group is electrophilic and undergoes reaction with a variety of nucleophiles.
  • This is because the leaving group has changed from hydroxide anion to water (the acidity of the conjugate acid H3O(+) is nearly that of HCl).

• Nucleophilic Substitution of the Hydroxyl Group

  • Clearly, an obvious step toward improving the reactivity of alcohols in SN2 reactions would be to modify the –OH functional group in a way that improves its stability as a leaving anion.
  • Since the hydronium ion (H3O(+)) is a much stronger acid than water, its conjugate base (H2O) is a better leaving group than hydroxide ion.
  • Nevertheless, the idea of modifying the -OH functional group to improve its stability as a leaving anion can be pursued in other directions.
  • In each case the hydroxyl group is converted to an ester of a strong acid.
  • All of these leaving groups (colored blue) have conjugate acids that are much stronger than water (by 13 to 16 powers of ten) so the leaving anion is correspondingly more stable than hydroxide ion.

• Molecularity

  • For example, if a crowd is leaving a theater through a single exit door, the time it takes to empty the building is a function of the number of people who can move through the door per second.
  • Once a group gathers at the door, the speed at which other people leave their seats and move along the aisles has no influence on the overall exit rate.

• Waxes

  • Waxes are esters of fatty acids with long chain monohydric alcohols (one hydroxyl group).
  • The leaves and fruits of many plants have waxy coatings, which may protect them from dehydration and small predators.