Synthesis of Alkyl Halides (Haloalkanes)

In this article we will learn about synthesis of Alkyl halides (Haloalkanes). 

Alkyl halides are the organic compounds which consists of halogen atom bonded to carbon atom. 

Key words: Alkyl halide, Haloalkane, Electrophilic addition, Radical substitution, Nucleophilic substitution.

Introduction

The alkyl halides are important compounds in organic synthesis because they are used for synthesis of various functional groups such as alkenes, alcohols, ethers, amines, nitriles etc. The alkyl halides are extensively used for synthesis of carbon-carbon bond by nucleophilic substitution of halogen.

The alkyl halides can be synthesized by alkane, alkene and alcohols. In this article we will discuss about basic methods for the synthesis of alkyl halides.

1.   Electrophilic addition

2.   Radical substitution

3.   Nucleophilic substitution

Let’s see each type of reaction in detail;

1.   Electrophilic addition

Alkyl halides are synthesized by addition reaction of alkene and halogen gas or hydrogen halides. The electrophilic addition of halogen gas on to alkene gives dialkyl halides. Similarly, addition of hydrogen halides on to alkene produces monoalkyl halide.

Fig 1:  Synthesis of alkyl halide from alkene

Example: 1

Hex-1-ene reacts with bromine gas to form 1,2-dibromobutane. This reaction is known as halogenation of alkene. The mechanism of reaction involves bromonium ion intermediate.

Fig 2: Reaction of hex-1-ene with brimine gas

In same way Hex-1-ene reacts with hydrogen bromide to produce 2-bromohexane. This reaction is known as hydrohalogenation of alkene. In this case highly substituted alkyl halide is favored. The mechanism of reaction consists of carbocation intermedicate.

Fig 3: Reaction of hex-1-ene with hydrogen bromide

2.   Radical substitution

Alkyl halides are synthesized from alkane by substitution of hydrogen with halide radical. In this type of reaction halogen gas reacts with alkane in presence of light to form alkyl halide. The reaction proceeds through formation of highly stable alkyl radical. 

Fig 4: Synthesis of alkyl halide from alkane

Example: 2

Fig 5: Reaction of isobutane with chlorine gas

The alkene containing allylic hydrogen are tends to undergo radical substitution reaction to produce allylic halide. Allylic radical is more stable than alkyl radical hence allylic halogenation is favored. 

Fig 6: Synthesis of allylic halide from alkene

Example: 3

Cyclohexene reacts with bromine gas to produce allylic bromide.

Fig 7: Reaction of cyclohexene with bromine gas

But in this reaction there is also addition of excess of bromine on to carbon –carbon double bond. Therefore to solve this problem researcher’s use N-Bromosuccinimide (NBS), this can produce bromine radical in the reaction mixture. Hence there will not be bromine addition of carbon-carbon double bond. 

Fig 8: Reaction of cyclohexene with N-bromosuccinimide (NBS)

3.   Nucleophilic substitution

The alcohols are used for the synthesis of alkyl halides. This conversion can be done by the reaction of alcohol and hydrogen halide. According to mechanism of the reaction; firstly hydroxyl group gets protonated to become good leaving group. Second step is formation of carbocation intermediate. Then the last step is nucleophilic attack of halide anion to form alkyl halide. This type of reaction is known as nucleophilic substitution reaction. 

Fig 9: Synthesis of alkyl halide from alcohol

Mechanism

Fig 10: Mechanism of synthesis of alkyl halide from alcohol

Example: 4

Fig 11: Reaction of 2,3-dimethylbutan-2-ol with HBr

The reaction proceeds through carbocation intermediate so there is possibility of rearrangement to form most stable carbocation. Let’s see this with an example;

Example: 5

In the reaction of 2-methylpropan-1-ol with hydrogen chloride; carbocation intermediate undergoes most stable tertiary carbocation. Then there is addition of chloride anion to form tertiary alkyl halide. 

Fig 12: Reaction of 2-methylpropan-1-ol with HCl (g)

To solve the problem of rearrangement in the intermediate, there is another method available for the synthesis of alkyl halide from alcohols. The reaction of alcohols with phosphorus trihalides gives alkyl halides. In this reaction carbocation intermediate will not form so there will not be any rearrangements in the final product.

Fig 13: Reaction of 2-methylpropan-1-ol with Phosphorus trichloride

Mechanism

Step 1:  Nucleophilic attack of lone pair of OH group on phosphorus followed by Cl anion removal.

Step 2: Conversion of OH into good leaving group. Then attack of Cl anion to from alkyl halide.

Fig 14: Mechanism of reaction of 2-methylpropan-1-ol with Phosphorus trichloride

In summary of above topic; we have seen few basic methods available for the synthesis of alkyl halides.

To understand the above methods please write the major product of the following reactions:

That's all for this topic. If you have any questions please feel free to ask me in the comment box. Thank you..!