Name: alcohols to halides: reagents and mechanisms
Uploaded: 2023-04-30T18:28:39.000Z
Duration: 2 min 48 s
Channel: JoVE

Alcohols react with hydrogen halides to generate corresponding alkyl halides.
In the mechanism, the first step is the protonation of the hydroxyl group. Thereafter, while tertiary alcohols interact via the SN1 mechanism, primary alcohols prefer an SN2 route. Secondary alcohols can proceed via either mechanism, where the preference is dictated by the reaction conditions.
Recall that an SN1 mechanism occurs sequentially: a loss of the leaving group, followed by the nucleophilic attack. Since this reaction proceeds via the carbocation intermediate, it is suitable for the tertiary carbocation, which is stabilized by hyperconjugation.
For primary alcohols, the protonation of the hydroxyl group leads to the SN2 mechanism. However, while the SN2 mechanism is straightforward with hydrogen bromide, hydrogen chloride needs an additional catalyst, zinc chloride.
Zinc chloride, being ionic, is limited to water-soluble alcohols. It converts their hydroxyl group into a better leaving group, enabling the subsequent SN2 process.
A more common process for primary alcohols uses thionyl chloride. A primary alcohol interacts with thionyl chloride in the presence of pyridine or a tertiary amine, which

conversion of alcohols to alkyl halides

Conversion of Alcohols to Alkyl Halides

This lesson delves into the conversion of alcohols to corresponding alkyl halides and the mechanism of action for different reagents. Typically, the hydroxyl group is first protonated to convert it to a stable leaving group. Consequently, based on the starting alcohol, the mechanism undergoes either of the nucleophilic substitution routes, SN1 or SN2. Tertiary alkyl halides are made using the two-step SN1 mechanism that occurs via a carbocation intermediate, which is stabilized by hyperconjugation. However, for primary alcohols, the protonation of the hydroxyl group leads to the concerted SN2 route. Secondary alcohols can proceed via either mechanism based on the reaction conditions.
The popular reagents used for converting alcohols to corresponding alkyl halides include the hydrogen halides like hydrogen bromide and hydrogen chloride. However, while it is straightforward with the former, the latter needs an additional catalyst like zinc chloride. This catalyzes the hydroxyl group into a better leaving group enabling the subsequent SN2 process. Other reagents of choice are thionyl chloride and phosphorus tribromide with a similar mechanism. In the presence of relatively weak bases like pyridine/tertiary amine, they generate an excellent leaving group compared to the original leaving group of water.
The most exciting class of reagents is sulfonyls. They react with the alcohols to form corresponding mesylates, tosylates, or triflates to improve their reactivity in an SN2 reaction. In these species, resonance stabilization is inherent to the sulfonyl group. Additional resonance stabilization is contributed by the benzene ring of the tosyl group, and further stability is provided by the strongly electron-withdrawing trifluoromethyl in the triflate.
<h4>Stereochemistry</h4>
Most importantly, the choice of reagent influences the stereochemistry of the product formed. The use of thionyl chloride leads to an inversion of configuration, while tosyl chlorides retain the chiral configuration in the native alcohol.

This lesson delves into the conversion of alcohols to corresponding alkyl halides and the mechanism of action for different reagents. Typically, the ...

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JoVE Core

Organic Chemistry

Unit 1

Alcohols and Phenols

KEY TERMS AND CONCEPTS

alcohols to halides: reagents and mechanisms

Alcohols can be turned into alkyl halides by using reagents that make the hydroxyl group a better leaving group. The hydroxyl group is first protonated, which helps the reaction move forward. From there, the pathway can follow either an SN1 or SN2 substitution, depending on the starting alcohol and the reaction conditions.

Tertiary alcohols usually form tertiary alkyl halides through a two-step SN1 mechanism. This route goes through a carbocation intermediate, and hyperconjugation helps stabilize that charged species. Primary alcohols usually follow the concerted SN2 route after protonation of the hydroxyl group. Secondary alcohols can go by either pathway, based on the conditions used.

Several reagents are commonly used for this transformation. Hydrogen bromide and hydrogen chloride are important examples, but hydrogen chloride usually needs zinc chloride as an added catalyst. The catalyst helps turn the hydroxyl group into a better leaving group so the SN2 reaction can occur. Thionyl chloride and phosphorus tribromide work in a similar way, often in the presence of weak bases such as pyridine or a tertiary amine.

Sulfonyl reagents provide another useful route because they convert alcohols into mesylates, tosylates, or triflates. These groups are much better leaving groups than water in an SN2 reaction. Their reactivity comes from resonance stabilization in the sulfonyl group. The tosyl group gets extra stabilization from its benzene ring, and the triflate is further stabilized by its strongly electron-withdrawing trifluoromethyl group.

The reagent also affects stereochemistry. Thionyl chloride causes inversion of configuration, while tosyl chlorides retain the chiral configuration in the original alcohol. This makes reagent choice important not only for reactivity, but also for the final 3D arrangement of the product.

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organic chemistry

JoVE Core Organic Chemistry explains basic concepts of stereochemistry, reactions, and mechanisms using concise and easy-to-understand animated video lessons. Additionally, the scientist-in-action videos demonstrate the application of related concepts in classical and original research experiments performed in today's laboratories worldwide.

Alcohols to Halides: Reagents and Mechanisms

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