Other Important Halogenation Methods

In organic synthesis, Halogenation is the addition of molecular halogens such as Chlorine, Iodine, Bromine, or Fluorine. There are several ways to Halogenate the organic compounds, including radical halogenation, halogen addition reaction, and electrophilic halogenation.

Why is halogenation important?

Halogenation is important because it adds functionality to a carbon chain. Hydrocarbons that are pumped from the ground are unreactive molecules. Halogen reactions are important because the products generated with halogenation reactions are widely used in pharmaceuticals, plastics, refrigerants, fire retardants, agro products, polymers, chlorine, Fluorine, iodine, and Bromine come under halogens. All of them have seven electrons to other non-metals. 

They have a low boiling and melting point compared to other non-metals. They are not good thermal and electricity conductors. All halogen elements expand their shell to include valence electrons, except Fluorine. 

Halogenation is heavily used in pharmaceuticals, such as for their therapeutic use from Fluorine and Chlorine. Acting as useful intermediate compounds, Organicbromides and Organiciodine give a meaningful addition of functional groups to a substance. 

For instance: C-Cl can be broken down by a chemical reaction with water to alcohols which further combines with oxygen to yield ketones, aldehydes, and acids. 

Similarly, double bonds can be easily formed by performing elimination reactions. 

For making a Grignard Reagent, treating organic compounds with Bromine is an important part of the reaction, which offers an artificial pathway to build carbon-carbon bonds. 

Some important economic chemicals and products arise from halogenation reactions. For example, to yield PTFE, Chloroform is introduced to Fluorine to form Chlorodifluoromethane, which is further converted to fluoroethylene and gives PTFE. 

Similarly, to yield PVC, the addition of ethylene with chlorine forms dichloroethane, further polymerized into PVC.

Halogenation reactions may involve using a catalyst to increase the chances of a halogen behaving as an electrophile. 

For example, Aromatic compounds require electrophilic substitution reactions. 

In the case of Bromine and Chlorine not being sufficiently electrophilic, they require the assistance of Lewis acid as they increase the polarity of the halogen for bonding. When a halogen is polarised, the positively charged halogen becomes a stronger electrophile and capable enough to complete the substitution of hydrogen in a substitution reaction.

Some examples of catalysts used for the halogenation of aromatic rings are AlCl3or AlBr3. For Halogenation of Iodine, an oxidizer such as Nitric acid is required.

Since Fluorine is highly electronegative, it does not require a catalyst. In fact, in the substitution reaction, Fluorine can behave abruptly and halogenate the aromatic ring more than needed. 

Synthetic chemistry offers a broad scope in halogenation and is extremely useful for reactions. Treating aldehydes and Ketones with Chlorine, Bromine and Iodine in the alpha position is direct; however, treating with Fluorine is impossible. 

The alpha-hydrogen of a carboxylic acid is halogenated with Bromine or Chlorine via Zell-Volhard-Zelinsky reaction. Still, the help of a catalyst like P or PBr3 is important for the reaction to proceed.

Halogenation can occur easily when an enol is a substrate. For this very reason, alpha-halogenation of acyl halides, anhydrides, and malonic esters can occur without a catalyst. 

The Hoffman reaction converts amine to amide with the help of Bromine. 

Similarly, a catalyst like FeCl3 or AlCl3 or AlBr3 is required to Halogenate aromatic rings with Bromine or chlorine. Likewise, Alkene and Alkynes are instantly halogenated with Bromine or Chlorine. 

Fluorine requires no help from a catalyst for Halogenation. Still, reagents like ClOF3 can be used in the case of halogenating with phenols. 

Halogenation with a halogen molecule and hydrogen halides is utilised, but the results are dangerous, corrosive and difficult to manage. 

For instance, F and HF are extremely corrosive, reactive and produce unnecessary side products and are difficult to handle and control their reaction exothermically. 

Due to this reason, compounds like diethylaminosulfur trifluoride (DAST) have been developed to give a fluorine atom in a more stable and controlled environment. With the help of DAST, alcohols, aldehydes and ketones can be easily converted to organofluorine more safely and conveniently. 

Similarly, SOCl2 and PCl5 help stabilise elemental chlorine for producing organochlorine. 

In the case of Bromine, N-bromosuccinimide (NBS) is used to halogenate alkene. 

Halogenation Example: 

Synthesis of Acyl Fluorides 

In the presence of reagent (Me4N)SCF3, one can prepare acyl fluorides from reacting alkyl and aromatic carboxylic acids. 

Unlike HF or C3F3N3 This reagent is stable, enabling Halogenation with Fluorine.

Radical C-H Fluorination

Benzylic C-H is halogenated with Fluorine using unsafe amino acids to generate a radicle. Meanwhile, suppose we use a silver catalyst and Selectfluor (the source of electrophilic Fluorine). In that case, oxidative decarboxylation of the unsafe amino acids gives alpha-amino alkyl radicals. 

Free Radical Halogenation 

Free radical chlorination is used for the tailored manufacturing of solvents in the industry. 

CH4 + Cl2  →  CH3 + HCl

Addition of halogens to alkynes and alkenes 

RCH =  CHR’ + X2  → RCHX-CHXR’

In oxychlorination, the combination of hydrogen chloride and oxygen performs as similarly as chlorine to obtain dichloroethane:

2 HCl + CH2 = CH2 + ½ O2  →   ClCH2CH2Cl + H2O

Bromination of an alkene from trichloroethylene is the path to obtaining the halothane from an anaesthetic. 

Halogenation of Aromatic Compounds

Aromatic compounds are a point to electrophilic Halogenation.

Halogens are added to unsaturated compounds like alkene and alkynes. 

RC6H5 + X5   →   HX +  RC6H4X

Other Halogenation Methods

In the Hunsdiecker reaction, Carboxylic acids are converted to a halide whose reduced carbon chain. Firstly, the carboxylic acid is converted to silver salt, further oxidised with halogen.

RCO2Ag + Br2  →  RBr + CO2 + AgBr

These were some examples of how Halogenation is conducted. 

Conclusion

The standard Halogenation methods of organic compounds can raise serious environmental issues. Furthermore, these methods are quite heavy on the wallet. Halogenation can create many useful compounds, though preparing them is dangerous and unsafe in many conditions. Less reactive halogens are somewhat easier to react to than Fluorine. Halogenation can be performed in substitution, addition and electrophilic, free radical reaction. Around us, Halogenation has a wide variety of uses such as fire retardants, imaging in medical diagnosis, production of polymers, drugs, etc.