Wolf-Kishner Reduction in one shot - reaction mechanism and medical use in synthesis of ibuprofen

[00:00:05]Sir, we did it. We have finally created the drug. Now it's time to test it.

[00:00:14]Good. But before testing on anybody else, we are going to try this on me.

[00:00:22]These people in the above frame are none other than the British pharmarmacologist Dr. Steuart Adams and organic chemist John Nicholson who who discovered the famous drug ibuprofen in 1961 in Nottingham, UK.

[00:00:41]The drug ibuprofen is widely used in relieving pain, reducing inflammation and also helps in reducing fever.

[00:00:54]But do you know the reaction used in synthesis of ibuprofen?

[00:01:00]The reaction is named as Wolf Kishner reduction reaction.

[00:01:05]Wolf Kishner reduction reaction is basically the reduction of carbonial group of aldahhides and ketones to methylene CH2 group using hydroine NH2 NH2 followed by heating with sodium or potassium hydroxide NaOH or KOH in high boiling solvent like ethylene glycol.

[00:01:32]Now the question arises that how does this reaction proceed? Why is the carbonial group changing into an entirely different CH2 group?

[00:01:43]Let's try to find out organic reaction mechanism.

[00:01:58]Step one, nucleophilic addition of hydroine to form hydroone.

[00:02:06]In this step, hydroine undergoes nucleophilic addition to central carbon of carbonial group due to which double bonded O reduces to single bonded O minus. As O minus has negative charge on it, it attracts an H+ ion from NH2 NH2 group internally forming O.

[00:02:34]Now O along with H+ from NHNH2 are removed as they both together form H2O and H2O is a good leaving group. So it leaves leading to the formation of hydroone.

[00:02:51]Step two, heating hydro zone with a base particularly NaOH or KOH.

[00:02:57]Now hydroone is heated with base NaOH or KOH where O minus takes an H+ ion from double bonded NNH2 group where they form H2O and as H2O is a good leaving group it is removed. Also the double bond shifts from between carbon and nitrogen to between two nitrogen atoms.

[00:03:24]Now as N double bond N group or N2 group has formed here it leaves forming a carb annion. As N2 group is considered one of the best leaving groups.

[00:03:37]Step three protonation of the resulting carbanion to alkan. In this step, an H+ ion is added to the carb annion or carb anon is protetonated to form alkan.

[00:03:54]Now after understanding the mechanism of wolf Kishner reduction and learning that it is used in ibuprofen, a question arises how does this reaction help in the synthesis of ibuprofen?

[00:04:08]Let's try to find out.

[00:04:10]First let's talk about the organic name of ibuprofen.

[00:04:15]Organic name of ibuprofen is 24 isobutal fennel proponinoic acid. In traditional multi-step ibuprofen synthesis, the wolf kishner reduction is used to convert intermediate aerocetone pisobutal acettophenon into the final carbon skeleton isobutal benzene by completely removing the carbonial oxygen C double bonded O and replacing it with two hydrogens CH2.

[00:04:48]Isobbutylbenzene is then converted to two four 2methyl propylphenol propinoic acid or ibuprofen by through a multi-step process by fridal crafts isolation Darzen's condensation and hydraysis quick bites. One, ibuprofen is a great medicine or drug which has significant medical uses, but it do arise with some side effects like upset stomach, nausea, dizziness, and heartburn. Excessive use of ibuprofen can also lead to swelling in hands, ankles, or feet. Two, when performing a Wolfkishner reduction, the primary safety and experimental precautions focus on handling hydroine, managing high heat, typically around 200° C, and avoiding base sensitive functional groups.