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Wolff–Kishner reduction is an organic chemistry process that transforms carbonyl groups into methylene groups. A carbonyl group is most typically removed after serving its synthetic goal of activation as an intermediate in previous steps in the context of compound molecule synthesis. As a result, this response has no evident retron. Nikolai Kischner and Ludwig Wolff reported the reaction in 1911 and 1912, respectively. Huang’s modification was a significant enough improvement that it eventually replaced the original approach for the Wolff-Kishner reactions developed. It is possible to achieve high temperatures (180—210°C) in the Huang-Minlon variation of the Wolff-Kishner process without using pressure equipment.
Wolf-Kishner Reduction and Huang Minlon Modification
During the Wolf-Kishner reduction, the carbonyl substrate is condensed with the presence of hydrazine intermediate. In the early 19th century, Ludwif Wolff and Nikolai Kishner developed this reduction reaction. In 1911, N.Kishner performed a reaction on an already-formed hydrazone in the presence of heated potassium hydroxide, which comprised a platinised porous plate that had been crushed. Hydrazones and sodium ethoxide were heated to 180 °C in a sealed tube by Wolf in 1912.
Wolff-Kishner reduction is the reaction that is still frequently used to reduce a ketone to its corresponding alkane. This reduction is frequently modified using the Huang-Minlon method. It requires treating the ketone with the presence of hydrazine hydrate and potassium hydroxide in diethylene glycol at a low temperature and subsequently at a high temperature and under reflux. Due to its high boiling point, ethylene glycol is utilised to eliminate nitrogen gas, a byproduct of the reaction. Among the benefits of the modification is the synthesis of pure products with a higher yield than with the original reaction and the ability to use sterically hindered ketones in the same process.
Mechanism of Actions:
The Wolff–Kishner reduction mechanism has been explored by Szmant and others. The carbonyl substrate condenses with hydrazine to generate an intermediate hydrazone in this reaction. The carbonyl substrate is transformed into a hydrazone derivative through a nucleophilic reaction of hydrazine with the carbonyl group. This step takes a long time and is called the rate-determining step. Then, in the presence of a base, the Nitrogen in the hydrazone is deprotonated, and the deprotonated hydrazone goes through protonation. Then Nitrogen is deprotonated, resulting in the formation of carbanion and the emission of nitrogen gas. Finally, the carbanion receives a proton from water, resulting in the formation of the alkane product.
The Wolff-Kishner reduction is a widely applicable method for deoxygenating carbonyl compounds. The Huang-Minlon modifications were performed in a single-pot procedure, whereas the earlier reductions were two-step operations on hydrazone or semicarbazone derivatives. In this technique, base and proton sources are used with a carbonyl group and hydrazine to heat them to 180-220 degrees Celsius. Frequent bases include sodium or potassium hydroxide, potassium-t-butoxide, and other alkoxides, while ethylene glycol or its oligomers serve as the solvent and proton source. Throughout the years, numerous modifications of this process have been implemented to accommodate the particular requirements of a given substrate. Nevertheless, the Wolff-Kishner reduction is the reaction, most widely used method for preparing alkanes from carbonyls and works well on both aldehydes and ketones.
Modifications:
Wolff–Kishner reduction improvement efforts have concentrated on removing water from the hydrazone intermediate and raising the temperature of the reaction to increase the rate of hydrazine decomposition. Some of the most recent modifications make more substantial improvements and enable reactions under substantially milder conditions.
Huang-Minlon Modification:
The Huang-Minlon Modification is named after Huang Minlon, the first organic reaction connected to a Chinese chemist. However, a common misconception about Huang-Minlon is that his name refers to two people due to the unusual spelling of his given name in the initial reports on his discoveries “Huang-Minlon.” Huang Minlon published 1946 a modified method for the Wolff–Kishner reductions of ketones, in which surplus hydrazine and water were eliminated by distillation following hydrazone production.
Even when using anhydrous hydrazine, the temperature-lowering effect of water leads to long reaction durations and severe reaction conditions. Using a modified process, the carbonyl compound is refluxed in an 85 per cent hydrazine hydrate solution with three equivalents of sodium hydroxide, accompanied by distillation of the water and excess hydrazine and heating to 200 degrees Celsius. Using this modification, it is possible to get considerably shorter reaction times and higher yields. The initial study by Huang Minlon documented the reduction of β-propionic acid to γ-butyric acid with a yield of 95 per cent, compared to 48 per cent using the conventional process.
The benefits of this modification include
a) Anyone can easily carry out the reaction.
b) It is possible to separate just pure products.
c) Ketones that are sterically inhibited can also be decreased.
Conclusion:
Using the Wolff-Kishner reduction, aldehydes and ketones can be deoxygenated to their hydrocarbon equivalents. There have been numerous suggestions for changes to the original protocols. The Huang-Minlon modification used hydrazine hydrate instead of anhydrous hydrazine, which is safer and less expensive. In the Huang Minlon reduction reaction, carbonyl compounds were heated strongly with KOH solution and hydrazine hydrate in ethylene glycol. One of the side products of this reaction is nitrogen gas, which must be quickly evacuated from the reaction vessel. A solvent with a high boiling point, such as ethylene glycol, is required to remove the gas. This procedure is preferred for the synthesis of both polycyclic and hindered alkanes.
