User:Tsang Karl/Ketone Halogenation

Article body:
 Halogenation using Conventional methods 

 Process 

Halogenation of saturated ketones usually occurs through replacement of hydrogens that are alpha to the carbonyl group. The most common reagent to accomplish the change are halogenated alkanes such as Cl2, Br2, SO2Cl2, and N-bromoimide. This can occur in an acidic or basic solution.

In an acid catalyzed process, the reaction first begins with the ketone being tautomerized to form the enol through an acidic medium. This step is the Rate-determining step of the reaction as it is the slowest. Following this, the enol acts as a nucleophilic source to allow for the addition of an halogen to the alpha position. Typically, for acidic conditions halogenation for Ketones stops after one addition.

In basic conditions, this reaction proceeds through an enolate intermediate upon the deprotonation of the ketone. Afterwards, the enolate will add to the halogen and displace the other halogen anion similar to Sn2 like mechanism.

However, in basic conditions, haloketones are susceptible to over-halogenation due to the product being more reactive than the starting materials, which will result in further addition to the ketones. Typically, if you have a methyl ketones, all of the hydrogens on the methyl group will exchange with halogens, as it's very difficult to control halogenation under basic conditions. In situ, this trihalogenated ketone is susceptible to nucleophilic attack from hydroxide ions, which is called the haloform reaction, and results in the formation of carboxylate ions. This can be isolated as an carboxylic acid upon workup.

Note: Acidic mechanism needs to be rewritten on original article as the first step should be shown stepwise.

 Halogenation of α,β-Unsaturated Ketones 

On α,β-Unsaturated ketones or enones, it's possible to halogenate with iodine selectively on the more saturated alpha on the ketone selectively over the unsaturated side. Iodine is preferred due to it being more reactive than alkyl bromides which makes this reaction quite useful. By using an CuO in junction with I 2 it is possible to achieve this reaction with relatively mild conditions. This reaction does go to a very reactive enol mechanism, facilitated by the CuO, which will allow for the selective addition of I2 on the unsaturated alpha carbon of the ketone. However, the effectiveness of this reaction depends on the presence of aryl functional groups.

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 Application of Green Chemistry 

Alpha halogenated products are very useful compounds as they have high reactivity which makes them very prone to reacting. Alpha halogenated ketones react with nucleophiles to create many valuable compounds. However, many of the current processes for the formation of halogenated ketones use hazardous chemicals, have complicated procedure, and require a long time to go to completion. Additionally, the polar solvents that are primarily used (DMF, DMSO, and CH3CN) are major pollutants to the environment.

An important aspect too many processes today, is that they follow the principles of green chemistry. An experiment conducted by Meshram et al. in 2005 investigated making ketone halogenation a green reaction. An alternative to the hazardous chemicals that are primarily used is looked into by Meshram et al. and it was found that room temperature ionic liquids were a promising option. Room temperature ionic liquids are interesting prospects as they have unique chemical and physical properties, and their properties can be modified by changing the cations that are attached. Additionally, these ionic liquids have high polarity and their ability to solubilize organic and inorganic molecules leads to enhanced reaction rates, which makes them more desirable.

Many experiments found that ionic liquids with N-halosuccinimides as the solvent were a very effective alternative and also used the principles of green chemistry. This process also enhanced yields, shortened the reaction time, simplified the procedure, used less harmful chemicals (no strong acid), and avoided the need for a catalyst, which made the process greener.