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

Properties of Alkyl Halides

Alkyl halide (or haloalkane):

A chemical compound containing a halogen atom bonded to an sp3 hybridized carbon atom. The 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

Nomenclature of Alkyl Halides

How to name an alkyl halide:

An alkyl halide is named like 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 the different prefixes, and commas to separate numbers
    - arrange the substituents in alphabetical order (di, tri, tetra are not counted)

 

Polar Reactions

Electrophile vs. Nucleophile

  • Electrophile: a species poor in electrons. It can be neutral or positively charged and is usually symbolized by E+
  • Nucleophile: a species rich in electrons. It can be neutral or negatively charged and is usually symbolized by Nu-

 

Polar Reactions

Reactions that occur between an electrophile and a nucleophile. Certain 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 thus have only 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. A σ bond is broken and a σ bond is formed. 2 mechanisms are possible: SN1 and SN2
 

 

Examples of nucleophiles and leaving groups:

Good nucleophile (Nu-): cyanide (-CN), thiolate (RS-), alkoxide (RO-)
Good leaving group: halide (I-, Br-), water (H2O), tosylate (TsO-)

SN2 Reactions

SN2 reactions:

Nucleophilic substitutions that do not proceed through an intermediate ⇒ SN2 reactions are bimolecular with simultaneous bond-making and bond-breaking steps. The kinetic rate of an SN2 reaction involves 2 components: the nucleophilic reagent and the electrophilic reagent


Mechanism:

Because of its unique step, the 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 that proceed through a carbocation intermediate ⇒ SN1 reactions are unimolecular with a bond-breaking step followed by a bond-making step. The kinetic rate involves only 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. Because of the planar carbocation intermediate, SN1 reactions result in a racemization of the stereochemistry in the reaction center (nucleophiles can attack from both sides)

 



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

 

Factors Favoring SN1 or SN2

Alkyl halide

The nature of the alkyl halide is the most important factor in determining whether a reaction follows the SN1 or SN2 mechanism:

  • Methyl halides (CH3X) and primary halides (RCH2X) ⇒ SN2 reactions only
  • Tertiary halides (R3CX) ⇒ SN1 reactions only
  • Secondary halides (R2CHX) ⇒ both SN1 and SN2 reactions. Other factors such as the strength of the nucleophile and the polarity of the solvent determine the mechanism

 

Primary halide ⇒ SN2 reaction 

Secondary halide ⇒ SN1 and SN2 reactions

Tertiary halide ⇒ SN1 reaction 

 

Nucleophile

The rate of the SN1 reaction is not affected by the nature of the nucleophile because it does not appear in the rate equation. However, the nature of the nucleophile is important for the SN2 reaction:

  • Strong nucleophiles (usually a molecule with a net negative charge such as HO-, RO-, RS-) favor SN2 reactions
  • Weak nucleophiles (usually neutral molecules such as H2O, ROH) favor SN1 reactions by decreasing the rate of any competing SN2 reactions

 

 

Solvent

  • Polar protic solvents (H2O, ROH, RCOOH) favor SN1 reactions because the carbocation intermediates are stabilized by solvation
  • Polar aprotic solvents (CH3CN, ROR, DMSO) favor SN2 reactions because the nucleophiles are not well solvated and are therefore more nucleophilic

 

 

Summary SN1 vs. SN2 Reactions

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 has no importance

favored by polar protic solvents

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

favored by polar aprotic solvents

Check your knowledge about this Chapter

An alkyl halide or haloalkane is a chemical compound containing a halogen atom bonded to an sp3 hybridized carbon atom. The halogens are the elements occupying group VIIA (17) of the periodic table: fluorine, chlorine, bromine, iodine, and astatine

The general formula for alkyl halides is R-X where R = alkyl group and X = halogen atom

Halogens are more electronegative than carbon atoms. Therefore, the electron density along the C–X bond of an alkyl halide is shifted towards X ⇒ the C–X bond is polar. Alkyl halides exhibit dipole-dipole interactions due to the polar C-X bond

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 ⇒ characteristic reactions are substitutions and eliminations, respectively

The bond strength of C–X decreases as the size of X increases ⇒ iodine is a better leaving group than fluorine. Alkyl iodide is the most reactive alkyl halide

An alkyl halide is named like 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 the different prefixes, and commas to separate numbers
    - arrange the substituents in alphabetical order (di, tri, tetra are not counted
  • Electrophile: a species poor in electrons. It can be neutral or positively charged and is usually symbolized by E+
  • Nucleophile: a species rich in electrons. It can be neutral or negatively charged and is usually symbolized by Nu-

A polar reaction occurs between an electrophile and a nucleophile. Certain 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

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

A nucleophilic substitution reaction or SN reaction is a class of reactions in which a nucleophile attacks an electrophile to replace a good leaving group on an sp3 hybridized carbon. A σ bond is broken and a σ bond is formed. 2 mechanisms are possible: SN1 and SN2
 

  • Good nucleophile (Nu-): cyanide (-CN), thiolate (RS-), alkoxide (RO-)
  • Good leaving group: halide (I-, Br-), water (H2O), tosylate (TsO-)

SN2 reactions are nucleophilic substitutions that do not proceed through an intermediate ⇒ SN2 reactions are bimolecular with simultaneous bond-making and bond-breaking steps. The kinetic rate of an SN2 reaction involves 2 components: the nucleophilic reagent and the electrophilic reagent

Because of its unique step, the SN2 reaction results in an inversion of configuration at the reaction center. The nucleophile attacks the electrophilic 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
 

SN1 reactions are nucleophilic substitutions that proceed through a carbocation intermediate ⇒ SN1 reactions are unimolecular with a bond-breaking step followed by a bond-making step. The kinetic rate involves only the starting material

In the first step, the leaving group leaves, forming a carbocation. In the second step, the nucleophile attacks the carbocation to give the product. Because of the planar carbocation intermediate, SN1 reactions result in a racemization of the stereochemistry in the reaction center (nucleophiles can attack from both sides)
 

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 has no importance

favored by polar protic solvents

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

favored by polar aprotic solvents

The 3 factors that influence SN reactions are:

  • The nature of the substrate (in this chapter an alkyl halide)
  • The strength of the nucleophile
  • The polarity of the solvent

The nature of the alkyl halide is the most important factor in determining whether a reaction follows the SN1 or SN2 mechanism:

  • Methyl halides (CH3X) and primary halides (RCH2X) ⇒ SN2 reactions only
  • Tertiary halides (R3CX) ⇒ SN1 reactions only
  • Secondary halides (R2CHX) ⇒ both SN1 and SN2 reactions. Other factors such as the strength of the nucleophile and the polarity of the solvent determine the mechanism

Steric effects are particularly important in SN2 reactions. Due to their small steric hindrance and lower stability of primary carbocations, primary alkyl halides favor SN2 reactions over SN1 reactions

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

The rate of the SN1 reaction is not affected by the nature of the nucleophile because it does not appear in the rate equation. However, the nature of the nucleophile is important for the SN2 reaction:

  • Strong nucleophiles (usually a molecule with a net negative charge such as HO-, RO-, RS-) favor SN2 reactions
  • Weak nucleophiles (usually neutral molecules such as H2O, ROH) favor SN1 reactions by decreasing the rate of any competing SN2 reactions
  • Polar protic solvents (H2O, ROH, RCOOH) favor SN1 reactions because the carbocation intermediates are stabilized by solvation
  • Polar aprotic solvents (CH3CN, ROR, DMSO) favor SN2 reactions because the nucleophiles are not well solvated and are therefore more nucleophilic