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Mastering the Conversion of OH Groups to Alkyl Halides

Converting an OH Group to a Good Leaving Group: Approaches and Techniques

Organic chemistry deals with the study of compounds containing carbon and their properties, reactions, and synthesis. One of the most fundamental concepts in organic chemistry is functional groups, which are specific groups of atoms within a molecule that determine the molecule’s chemical properties and reactivity.

The hydroxyl (OH) functional group is among the most common and critical functional groups in organic chemistry. This article focuses on the conversion of OH groups to good leaving groups, the limitations of using hydrogen halides (HX) as reagents, and alternative methods for converting OH groups.

Approach 1: Conversion of Alcohols to Alkyl Halides with HX

Alcohols, represented by the general formula ROH, are functional groups with an OH group attached to an alkyl or aryl group. Due to the polar nature of the OH group, alcohols have a higher boiling point and are more soluble in water than their corresponding alkyl halides.

One way to convert alcohols to alkyl halides is through the addition of hydrogen halides such as hydrochloric acid (HCl), hydrobromic acid (HBr), or hydrogen iodide (HI). The conversion of alcohols to alkyl halides via HX is known as a substitution reaction, which proceeds through the S N 2 mechanism.

In an S N 2 reaction, the hydroxyl ion (OH-) acts as a nucleophile, attacking the alkyl halide from the opposite side of the halogen atom. This mechanism is favored for primary and methyl alcohols since these compounds give primary alkyl halides, which have a higher tendency to undergo S N 2 reactions.

Approach 2: Activating the OH with Other Functional Groups

While conversion of OH groups to alkyl halides via HX is an effective method, it often comes with several limitations that limit its applicability. One significant challenge is poor selectivity, leading to the formation of mixtures of products with undesired stereochemistry.

This leads to the adoption of alternative methods to create better leaving groups by activating the OH group via other functional groups.

Tosylates and Mesylates

Sulfonate (RSO3-) or sulfonyl chlorides (RSO2Cl) can be used to activate the OH group. These functional groups act as substitutes for the OH group, creating intermediates known as tosylates (ROSO2R’) and mesylates (ROSO2R”), respectively.

These intermediates are excellent leaving groups because they stabilize the negative charge that is created upon leaving. The formation of tosylates and mesylates can be achieved via tosylation and mesylation reactions, involving the use of a strong base and the sulfonating agent.

Conversion of Alcohols to Alkyl Halides with SOCl2 and PBr3

Thionyl chloride (SOCl2) and phosphorus tribromide (PBr3) are useful reagents that convert alcohols to alkyl chlorides and bromides, respectively. The reaction proceeds via the S N 2 mechanism and involves the formation of intermediates known as alkyl chlorides and bromides.

The reaction is useful for secondary and tertiary alcohols that are difficult to convert to alkyl halides via HX.

Disadvantages of using HX Acids

Although the conversion of OH to good leaving groups via HX is widely used in organic synthesis, it has some disadvantages that limit its applicability.

Unsuitability for Organic Molecules

HX acids are strong acids that can cause significant damage to organic molecules. They are not suitable for molecules that are sensitive to strong acidic conditions.

Additionally, they can destroy delicate functional groups, leading to low yields and poor reaction selectivity.

Lack of Stereochemical Control and Rearrangements

Conversion of OH groups to good leaving groups via HX may lead to low selectivity, with the formation of mixtures of products that have undesired stereochemistry. Furthermore, the reaction may cause rearrangements, leading to the formation of isomeric products.

These limitations affect the success of the reaction and restrict its use in various applications.


In summary, the conversion of OH groups to good leaving groups is a critical aspect of organic chemistry. Although conversion via HX is widely used, its limitations regarding selectivity and stereochemistry make alternative approaches such as tosylation/mesylation and SOCl2/PBr3 useful.

The organic chemistry community will continue to explore new methods to improve the efficiency, selectivity, and applicability of OH group conversion in organic synthesis. Conversion of Primary and Secondary Alcohols to Alkyl Halides: Mechanisms and Techniques

Alcohols are prevalent functional groups in organic chemistry, and their conversion to other functional groups is an important aspect of organic synthesis.

One common conversion of alcohols is to alkyl halides (RX), which are useful intermediates in various organic reactions. This article covers the mechanisms of converting primary and secondary alcohols to alkyl halides, the advantages of using sulfonates and sulfonyl chlorides, and the possibilities of reactions that involve these leaving groups.

S N 2 Mechanism for Primary Alcohols

Primary alcohols can be readily converted to primary alkyl halides via an S N 2 mechanism. In an S N 2 reaction, a nucleophile attacks the primary carbon attached to the OH group leading to the displacement of the OH group.

This mode of reaction requires the use of a strong nucleophile and polar aprotic solvent to reverse the polarity of the OH group and promote the displacement of the leaving group. This reaction is regioselective, and the newly formed alkyl halide is the result of the displacement of the OH group.

S N 2 and S N 1 Mechanism for Secondary Alcohols

Converting secondary alcohols to alkyl halides can proceed via two possible mechanisms: S N 2 or S N 1. The mechanism that governs the reaction depends on the specific conditions and the structure of the alcohol.

The S N 2 mechanism is favored for secondary alcohols and is used where high product selectivity is desirable. However, if the alcohol is highly branched, the reaction may proceed through a mechanism known as S N 1.

This mechanism, the substitution of a nucleophile with simultaneous ionization of the leaving group, leads to the formation of a stable carbocation intermediate. The carbocation intermediate may then undergo rearrangement to form a more stable carbocation, which leads to isomeric products.

This can be circumvented by using mild reaction conditions to maintain high selectivity.

Advantages of Using Sulfonates and Sulfonyl Chlorides

Sulfonates and sulfonyl chlorides offer specific advantages over HX in converting OH groups to alkyl groups. These advantages are discussed below:

Milder Conditions and Broader Range of Nucleophiles

One significant advantage of using sulfonates and sulfonyl chlorides over HX is that the reaction can proceed under milder conditions. For example, tosylates and mesylates are formed at ambient temperatures, and the reaction typically proceeds without the need for additional energy input.

A broader range of nucleophiles can also be used, including water or hydroxylamine, in addition to halide ions, under the same reaction conditions.

Possibilities for S N 1 and Elimination Reactions

Another advantage of using sulfonates and sulfonyl chlorides is the possibility of conducting S N 1 or elimination reactions. Conversion to sulfonates allows for the possibility of forming an alkyl sulfonate intermediate under S N 1 conditions.

This intermediate can go on to undergo substitution or elimination reactions, depending on the substrate and the reaction conditions. The ease of elimination can mean that the reaction provides an easy way to introduce carbon-carbon double bonds into a molecule.


Alcohol to alkyl halide conversion is an important aspect of organic synthesis. Understanding the mechanisms that govern such reactions is essential to successful process design, as is the selection of suitable leaving groups.

While it is possible to convert OH groups to alkyl groups using HX, sulfonates and sulfonyl chlorides are better in some cases due to the unique advantages they offer. The versatility of these reactions and the selective formation of various products demonstrate the enhancing effect of such techniques on modern chemical synthesis.

Comparison between SOCl2 and PBr3: Techniques and Limitations

The creation of alkyl halides is a crucial process in organic chemistry. Alcohols, with their hydroxyl (-OH) group, can be converted to alkyl halides (-RX), a process that frequently involves the use of thionyl chloride (SOCl2) or phosphorus tribromide (PBr3).

This article compares these two reagents regarding their performance and potential for conversion, with a particular focus on the conversion of 1, 2, and 3 alcohols.

Conversion of 1 and 2 Alcohols to their Corresponding Alkyl Halides

1- and 2-alcohols can be readily converted to their corresponding alkyl halides using either SOCl2 or PBr3. However, the stereochemistry of the product can be inverted during the reaction.

This inversion of chirality is dependent on the reaction mechanism and the intermediate structure, with different mechanisms for SOCl2 and PBr3 involvement. In the case of SOCl2, the reaction follows an S N 2 mechanism, and the OH group acts as a nucleophile to displace the chloride.

This inversion of configuration is highly unlikely and only occurs if the alcohols have an asymmetric center. Alternatively, PBr3 reactions result in the inversion of chirality due to its proclivity towards the formation of a three-membered intermediate known as a bromonium ion.

This intermediate is attacked from the opposite face relative to the leaving group, leading to the inversion of the stereochemistry.

Possibility of Converting 3 Alcohols with SOCl2

The reaction of SOCl2 with three-carbon alcohols requires mild reaction conditions to avoid the formation of significant rearrangement. However, the reaction can still proceed via a process involving acyl chlorides formation, followed by substitution of the chlorine by tertiary amine or carboxylate anions.

This serves as a precursor for carbonyl compounds (such as aldehydes and ketones), which are more thermally stable than alkyl halides under the same conditions. Thus, using SOCl2 to convert tertiary alcohols to their corresponding carbonyl derivatives is an alternative way of making use of SOCl2 as a reagent for converting 3-alcohols.


SOCl2 and PBr3 are valuable reagents for converting alcohols to their corresponding alkyl halides. Both reagents offer their own distinct features in different applications, with SOCl2 offering mild reaction conditions amidst the creation of acyl chlorides and PBr3 providing higher yields with inversion of stereochemistry.

The selection of reagents and conditions depends crucially on the targeted products and the requirements of the experimental conditions, guiding researchers selection between these two well-established and efficient reagents. In conclusion, the conversion of alcohols to alkyl halides is a fundamental process in organic chemistry.

Techniques such as using HX acids, sulfonates and sulfonyl chlorides, and reagents like SOCl2 and PBr3 play a crucial role in these conversions. While HX acids are commonly used, they lack selectivity and control over stereochemistry.

Sulfonates and sulfonyl chlorides offer milder conditions and broader nucleophile compatibility. SOCl2 and PBr3 are valuable reagents, with SOCl2 resulting in minimal stereochemistry inversion and PBr3 providing higher yields with inversion.

Understanding the mechanisms and advantages of these techniques is essential for researchers in the field and allows for more precise and controlled synthesis methods.

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