Alkyl Halides - Nucleophilic Substitutions | Organic Chemistry 1

Properties of alkyl halides and nucleophilic substitutions are studied in this chapter: physical properties and naming of alkyl halides, polar reactions, nucleophilic substitution reactions, in-depth study of SN reactions, competition between SN1 and SN2

Nomenclature of Alkyl Halides

How to name an alkyl halide:

An alkyl halide is named as an alkane with a halogen substituent. The -ine ending of the halogen atom is changed to the suffix -o

  1. Find the parent carbon chain containing the halogen

  2. Number the chain

  3. Name and number the substituents

  4. Write the name of the alkyl halide as a single word
    - use hyphens to separate different prefixes and commas to separate numbers
    - arrange the substituents in alphabetical order (di, tri, tetra are not counted)

 

Properties of Alkyl Halides

Alkyl halide (or haloalkane):

A chemical compound containing a halogen atom bonded to an sp3 hybridized carbon atom. Halogens are the elements occupying group VIIA (17) of the periodic table: fluorine, chlorine, bromine, iodine, and astatine

 

General properties:

  • Alkyl halides have higher boiling and melting points than corresponding alkanes
  • Alkyl halides are soluble in organic solvents but insoluble in water
  • The bond strength of C–X decreases as the size of X increases ⇒ iodine is a better leaving group than fluorine
  • Halogens are more electronegative than carbon atoms. Therefore, the electron density along the C–X bond is shifted towards X ⇒ the C–X bond is polar
  • Alkyl halides exhibit dipole-dipole interactions due to the polar C-X bond

 

Reactivity of alkyl halides:

The reactivity of alkyl halides is determined by the polar C-X bond. This polar bond makes the alkyl halides reactive towards nucleophiles and bases ⇒ the characteristic reactions are respectively substitutions and eliminations

Polar Reactions

Polar reactions occur between an atom poor in electrons (or electrophile) and an atom rich in electrons (or nucleophile). Some regions of a molecule can be poor or rich in electrons: they are created by the polarity of the bonds due to the difference in electronegativity of the bonded atoms
 

In blue: electrophilic atom
In green: nucleophilic atom

 

Polar reactions involve species that have an even number of valence electrons and therefore only have pairs of electrons in their orbitals (≠ radical reactions) ⇒ heterolytic cleavages occur during this process

Nucleophilic Substitution Reactions

SN Reactions:

Class of reactions in which a nucleophile attacks an electrophile to replace a good leaving group on an sp3 hybridized carbon. One σ bond is broken and one σ bond is formed. 2 mechanisms are possible: SN1 and SN2
 

 

Examples of nucleophiles and leaving groups:

Good nucleophile (Nu-): -CN (NaCN), RS- (NaSR), RO- (NaOR) ...
Good leaving group: I-, Br-, H2O, TsO- ...

SN2 Reactions

SN2 reactions:

Nucleophilic substitutions which do not proceed via an intermediate ⇒ SN2 reactions are bimolecular with simultaneous bond-making and bond-breaking steps. The kinetic rate of a SN2 reaction involves 2 components: the nucleophile and the electrophile reagents


Mechanism:

Because of its unique step, SN2 reaction results in an inversion of configuration at the reaction center. The nucleophile attacks the electrophile center on the opposite side of the good leaving group. The other substituents flip from one side to the other: this is the inversion of configuration

 

 

Steric effects are particularly important in SN2 reactions:

SN1 Reactions

SN1 reactions:

Nucleophilic substitutions which proceed through an intermediate carbocation ⇒ SN1 reactions are unimolecular with a bond-breaking step following by a bond-making step. The kinetic rate only involves the starting material
 

Mechanism:

In the first step, the leaving group leaves, forming a carbocation. In the second step, the nucleophile attacks the carbocation to give the product. Due to the planar intermediate carbocation, SN1 reactions result in racemization of stereochemistry at the reaction center (nucleophiles can attack from both sides)
The first step is slower and therefore determines the rate: it is the rate-determining step

 



The neighboring groups of carbocation are important: electron-donating groups (such as R groups) stabilize a positive charge. The more stable the intermediate carbocation, the faster the SN1 reaction. The nature of the nucleophile does not matter

 

SN2 vs. SN1

SN2 mechanism:

1 step

Rate = k [RX] [Nu-]  ⇒  second-order kinetics

backside attack of the nucleophile
⇒ inversion of configuration

inhibited by steric hindrance
⇒ SN2 faster with primary haloalkanes

favored by stronger nucleophiles

SN1 mechanism:

2 steps

Rate = k [RX]  ⇒  first-order kinetics

planar intermediate carbocation
⇒ racemization at a single stereocenter

the more stable the carbocation, the faster the reaction
⇒ SN1 faster with tertiary haloalkanes

the nature of the nucleophile does not matter