- Alkyl halides are organic compounds containing carbon – halogen bond.
- The polarizability of carbon – halogen bond greatly influences the chemical reactivity of alkyl halides.
- Alkyl halides undergo nucleophilic substitution reaction.
- Substitution reaction can follow SN1 or SN2 mechanisms.
- Both mechanisms follow different conditions and offer different products.
- Alkyl halides also form an important Grignard reagent which is commonly utilized to make carbon–carbon bonds. Thus, alkyl halides are important precursors to increase the carbon chain length.
- Keep reading for more facts about reactions of alkyl halides.
Haloalkanes or Alkyl Halides
Haloalkanes or commonly known as alkyl halides are organic compounds containing halogen atoms directly bonded to a carbon atom. They are derived from alkanes or alkenes. Halides are an important class of organic compounds being precursors in many organic syntheses. They find many industrial applications such as flame retardants, organic solvents, and propellants. The general structure of alkyl halides are represented as:
The nature of Carbon – Halogen bond
In an alkyl halide molecule, the carbon – halogen bond is made up of a sp3 hybrid overlapping with the p orbital of the halogen atom. Here the interesting point is the difference in electronegativity of carbon and halogen atoms. Halogens are known for their high electronegativity e.g. F & Cl. This induces dipolar character in carbon – halogen bond of alkyl halide. Thus, electron density along the C – X bond is more inclined towards halogen giving halogen partially negative charge and carbon partially positive charge.
Also, moving from top to bottom in the halogen group of the periodic table, the size of the p orbital increases. This means electronic clouds in halogen atoms are more diffused. This eventually influences the overlapping with carbon sp3 orbitals and hence the strength of carbon – halogen bond decreases from fluorine to iodine. It also changes the bond length of the C – X bond from fluorine to iodine, top to bottom.
Reactions of alkyl halides
This polar character of the C – X bond is responsible for some of the characteristic chemical reactions of alkyl halides. The partial positive charge at the carbon center guides the attack of nucleophiles and drives nucleophilic substitution reactions.
Nucleophilic substitution reactions
Nucleophile stands for “nucleus loving”. It is an atom or group of atoms that is rich in electron density and reacts (attacks) with electron-deficient sites. In the same way, electrophile (electron loving) is an electron-deficient atom or group of atoms seeking electrons. The nucleophilicity of a nucleophile depends upon its structure. Common nucleophile as listed here
|Very powerful nucleophile||I-, HS-, RS-||>105|
|Good nucleophile||Br -, HO-, RO-, CN-, N3-||104|
|Fair nucleophile||NH3, Cl-, F-, RCO2-||103|
|Weak nucleophile||H2O, ROH||1|
|Very weak nucleophile||RCOOH||10-2|
A substitution reaction where a nucleophile replaces another nucleophile is known as a nucleophilic substitution reaction. These substitution reactions are a characteristic feature of alkyl halides. As described earlier, the induced dipolar nature of the C – X bond creates partial positive & negative charges on carbon and halogen centers. Here in the presence of a strong nucleophile (stronger than already attached to carbon), incoming nucleophile replaces the halogen. A simple illustration is shown below:
This substitution reaction is greatly influenced by nature of attacking nucleophile, substrate, and leaving group. In primary or secondary alkyl halides, attack of incoming nucleophile and displacement of leaving group takes place in a single step, however, in bulky tertiary alkyl halides, attack of incoming nucleophile and displacement of leaving group takes place in two steps. Hence, these substitution reactions follow two different mechanisms known as SN1 and SN2 reactions.
SN2 reaction mechanism
A simple example of the SN2 mechanism is the reaction of methyl bromide with hydroxide ion (base). The attack of incoming hydroxide at a partially positively charged carbon center displaces the bromide. The formation of a new bond of hydroxide ion and cleavage of bromide bond to carbon center takes place in a single step. Actually, the nucleophile pushes off the leaving group from carbon. The kinetic data suggest that the rate of reaction is directly proportional to the concentration of both methyl bromide and hydroxide ion. Thus it is first order in each reactant and second-order overall reaction.
Rate of reaction = k [ CH3Br ] [ -OH ]
Therefore, is it a bimolecular reaction where both attacking nucleophile and substrate are involved in the formation of a transition state. In this transition state, carbon is bonded to both the incoming nucleophile and the departing leaving group. Such reaction is known as bimolecular nucleophilic substitution reaction denoted as SN2.
An interesting aspect of the SN2 mechanism is the 100% inversion of configuration at the reaction site. It means the incoming nucleophile attacks carbon from the side opposite to the leaving group. In the end, the incoming nucleophile gets attached to the position opposite to the leaving group. This can be shown as:
As mentioned earlier, primary, secondary & tertiary follow slightly different mechanisms in nucleophilic substitution reactions. For example, the rates of reaction for bromides of methyl, ethyl, isopropyl, and tert-butyl compounds are significantly different. Methyl bromide undergoes SN2 reaction quickly while tert-butyl bromide does not react to the same bromide anion. The reason for this behavior can be explained on the basis of steric hindrance. Methyl is a smaller group compared to tert-butyl. For methyl, the attack of incoming nucleophiles from the backside is relatively easy because the three hydrogens attached do not pose any hindrance to the attacking group. While in tert-butyl group, three bulky methyl groups are attached to the electrophilic carbon center offering steric hindrance (opposition) to the incoming nucleophiles.
SN1 reaction mechanism
As mentioned in the previous section, tert-butyl bromide does not undergo substitution via the SN2 reaction mechanism. These bulky halides actually undergo nucleophilic substitution reaction following a slightly different mechanism, called the SN1 mechanism.
The kinetic data shows that the rate of reaction depends only upon tert-butyl bromide. The nucleophile (water in the above equation) does not contribute to the rate of reaction. Adding even stronger nucleophiles does not influence the rate of reaction. The reaction thus follows first-order kinetics where the rate of reaction is independent of concentration and nature of nucleophile. Moreover, nucleophile does not participate in the rate-determining step. This reaction mechanism is called an unimolecular nucleophilic substitution reaction and is denoted as SN1.
The rate equation can be
Rate of reaction = k [ (CH3)3CBr ]
Thus reaction mechanism can be written as
In the first step, alkyl halide dissociates to form a carbocation and a halide ion. The formation of the carbocation is a fundamental feature of the SN1 mechanism.
The carbocation formed in the first step reacts rapidly with a water molecule (nucleophile). The step completes nucleophilic substitution and forms an oxonium ion.
The last step is a fast acid-base reaction. Here water acts as a base and removes the proton from oxonium ion to give the final product i.e. tert-butyl alcohol. It is clear that SN1 is an ionization mechanism.
Comparing SN2 vs SN1 mechanism
In summary, both mechanisms involve the formation of slightly different intermediates. The relative rate of reaction for SN1 and SN2 reactions changes by changing the alkyl group. We may characterize it as
SN1 reactivity: methyl < primary < secondary < tertiary
SN2 reactivity: tertiary > secondary > primary > methyl
SN2 is a bimolecular nucleophilic substitution reaction taking place in a single step while SN1 is a unimolecular substitution reaction taking place in more than one step. The order of reaction for both mechanisms is also different. Both pathways are important for the synthesis of various organic compounds.
Examples of nucleophilic reaction of alkyl halides
Preparation of ether via williamson synthesis
This is a traditional method of preparing ether using alkyl halides and alkoxide. The reaction is more successful when modeled towards SN2 mechanism conditions. That’s why ence methyl halides and other primary alkyl halides are the best starting point.
Preparation of amines
Alkylamines can be prepared by the reaction of alkyl halides and ammonia. The reaction if not controlled may proceed in further steps to further alkylation of amines making, monomethyl, dimethyl, and trimethyl derivatives.
Preparations of thiols
Sulfur is the element most like oxygen. The sulfur analogue of alcohols (R-OH) is called thiol (R-SH). These thiols are prepared by SN2 reaction where sulfur source e.g. thiourea can react with an alkyl halide to form urea and thiol. The reaction goes through an intermediate; isothiouronium salt that on hydrolysis forms thiol.
Other chemical reactions of alkyl halides
Preparation of Grignard reagent
The grignard reagent is an organomagnesium compound. It is the most important organometallic compound among the family members. It can be prepared directly by alkyl halide and magnesium in anhydrous diethyl ether solvent. This organomagnesium reagent act as bronsted base and is used in various organic syntheses. This is used to synthesize carbon–carbon bonds.
Dehydrohalogenation: Elimination reaction of alkyl halides
Dehydrohalogenation is the removal of elements of hydrogen halide (HX) from an alkyl halide. It is one the most easily utilized methods of preparation of alkenes by β elimination. The reaction is carried out in the presence of a strong base such as sodium hydroxide or potassium hydroxide in ethyl alcohol as a solvent.
This elimination reaction also depends upon the nature of the alkyl group and halide attached. Its rate of reaction increases with decreasing strength of carbon – halogen bond. Hence dehydrogenation increases for halides as
F < Cl < Br < I
That’s why alkyl iodides have more tendency to follow this elimination mechanism and form alkenes.
Books for further study
- Morrison, R. T., and R. N. Boyd. "Organic chemistry 5th edition." (1987).
- Cary, A, F. Organic Chemistry, 3rd edition, (1996).
- Volhardt K, P, C. Organic Chemistry, (1987).
- Smith M, B and March, J. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5th edition (2001).