Hell&#8211;Volhard&#8211;Zelinsky reaction is a method to convert carboxylic acids bearing &#945; hydrogen to &#945;-brominated carboxylic acids in the presence of a mixture of phosphorus tribromide and bromine, followed by hydrolysis.
Phosphorus tribromide acts as a catalyst&#8212;it is either added directly or generated in situ by the reaction of red phosphorus with bromine.
The reaction begins with the carboxylic acid and the catalyst interacting to generate the acid bromide and HBr.
HBr then catalyzes the enolization of acid bromide to its enol form, both of which exist in equilibrium.
The enol form acts as a nucleophile that undergoes an &#945; substitution reaction with bromine to form an &#945;-bromo acid bromide.
This active intermediate, upon treatment with water, undergoes hydrolysis to produce the desired &#945;-brominated acid.
If instead of water, alcohols or amines are used, the intermediate is converted to its respective &#945;-brominated acid derivative.

&alpha;-bromination of carboxylic acids: hell&ndash;volhard&ndash;zelinski reaction

The method to achieve &#945;-brominated carboxylic acids using a mixture of phosphorus tribromide and bromine is known as the Hell&#8211;Volhard&#8211;Zelinski reaction. The reaction is catalyzed by phosphorus tribromide, which can be used directly or produced in situ from red phosphorus and bromine. The mechanism comprises PBr3 catalyzed conversion of acid to acid bromide and hydrogen bromide. The acid bromide enolizes to its enol form in the presence of HBr. The nucleophilic enol attacks the bromine molecule to give an &#945;-bromo acid bromide. The resulting molecule, upon subsequent hydrolysis, yields the desired &#945;-bromo acid.

Learn by watching this video about α-Bromination of Carboxylic Acids: Hell–Volhard–Zelinski Reaction at JoVE.com

&amp;#945;-Bromination of Carboxylic Acids: Hell&amp;#8211;Volhard&amp;#8211;Zelinski Reaction

&alpha;-Bromination of Carboxylic Acids: Hell&ndash;Volhard&ndash;Zelinski Reaction

The method to achieve &#945;-brominated carboxylic acids using a mixture of phosphorus tribromide and bromine is known as the ...

-bromination-of-carboxylic-acids-hellvolhardzelinski-reaction

Education

JoVE Core

Organic Chemistry

Unit 1

&alpha;-Carbon Chemistry: Enols, Enolates, and Enamines

KEY TERMS AND CONCEPTS

reactivity of enols

Reactivity of Enols

Enols are a class of compounds where a hydroxyl group is attached to a carbon&#8211;carbon double bond, which implies that it is a vinyl alcohol. A ...

reactivity of enolate ions

Reactivity of Enolate Ions

Enolate ions are formed by the acid&#8211;base reaction of a carbonyl compound with a base. This leads to deprotonation of the &alpha; hydrogen atom, ...

types of enols and enolates

Types of Enols and Enolates

Aldehydes and ketones form enols, although only about 1% of the enol is present at the equilibrium for simple monocarbonyl compounds. The enol form is ...

enolate mechanism conventions

Enolate Mechanism Conventions

When a carbonyl compound is treated with a strong base, the &#945; position gets deprotonated to give a resonance-stabilized intermediate called an ...

regioselective formation of enolates

Regioselective Formation of Enolates

As depicted in the figure below, the unsymmetrical ketones can form two possible enolates:&#160; less substituted or more substituted enolates. Usually, ...

stereochemical effects of enolization

Stereochemical Effects of Enolization

The chiral &#945;-carbon of the carbonyl compound is the stereocenter of the molecule. As shown in the figure below, when such a carbonyl compound ...

acid-catalyzed &alpha;-halogenation of aldehydes and ketones

acid-catalyzed-halogenation-of-aldehydes-and-ketones

Acid-Catalyzed &alpha;-Halogenation of Aldehydes and Ketones

By replacing an &#945;-hydrogen with a halogen, acid-catalyzed &#945;-halogenation of aldehydes or ketones yields a monohalogenated product
In the first ...

base-promoted &alpha;-halogenation of aldehydes and ketones

base-promoted-halogenation-of-aldehydes-and-ketones

Base-Promoted &alpha;-Halogenation of Aldehydes and Ketones

&#945;-Halogenation of aldehydes and ketones is a reaction involving the substitution of &#945; hydrogens with halogens in the presence of a base.&#160; ...

multiple halogenation of methyl ketones: haloform reaction

multiple-halogenation-of-methyl-ketones-haloform-reaction

Multiple Halogenation of Methyl Ketones: Haloform Reaction

A method involving the transformation of methyl ketones to carboxylic acids using excess base and halogen is called the haloform reaction. It begins with ...

&alpha;-halogenation of carboxylic acid derivatives: overview

-halogenation-of-carboxylic-acid-derivatives-overview

&alpha;-Halogenation of Carboxylic Acid Derivatives: Overview

Unlike aldehydes and ketones, carboxylic acids do not readily participate in &#945; halogenation reactions via enols or enolate intermediates. However, ...

reactions of &alpha;-halocarbonyl compounds: nucleophilic substitution

reactions-of-halocarbonyl-compounds-nucleophilic-substitution

Reactions of &alpha;-Halocarbonyl Compounds: Nucleophilic Substitution

Nucleophilic substitution in &#945;-halocarbonyl compounds can be achieved via an SN2 pathway. The reaction in &#945;-haloketones is generally carried out ...

nitrosation of enols

Nitrosation of Enols

The nitrosation reaction is one of the methods of preparing 1,2-diketones. The enol tautomer of the starting ketone reacts with sodium nitrite in ...

c&ndash;c bond formation: aldol condensation overview

cc-bond-formation-aldol-condensation-overview

C&ndash;C Bond Formation: Aldol Condensation Overview

Aldol condensation is an important route in synthetic organic chemistry used to generate a new carbon&#8211;carbon bond under basic or acidic conditions. ...

base-catalyzed aldol addition reaction

Base-Catalyzed Aldol Addition Reaction

As depicted in Figure 1, base-catalyzed aldol addition involves adding two carbonyl compounds in aqueous sodium hydroxide to form a &#946;-hydroxy ...

acid-catalyzed aldol addition reaction

Acid-Catalyzed Aldol Addition Reaction

The aldol reaction of a ketone under acidic conditions successfully forms an unsaturated carbonyl as the final product instead of an aldol. The ...

dehydration of aldols to enals: base-catalyzed aldol condensation

dehydration-of-aldols-to-enals-base-catalyzed-aldol-condensation

Dehydration of Aldols to Enals: Base-Catalyzed Aldol Condensation

This lesson delves into the aldol condensation catalyzed by bases, where aldols undergo dehydration to enals. As shown in Figure 1, the &#946;-hydroxy ...

dehydration of aldols to enones: acid-catalyzed aldol condensation

dehydration-of-aldols-to-enones-acid-catalyzed-aldol-condensation

Dehydration of Aldols to Enones: Acid-Catalyzed Aldol Condensation

As shown in Figure 1, under acidic conditions, the &#946;-hydroxy ketone undergoes dehydration via an E1 elimination reaction to form an enone.

Figure 1. ...

intramolecular aldol reaction

Intramolecular Aldol Reaction

Intramolecular aldol reaction occurs in dicarbonyl compounds such as dialdehydes, diketones, and keto-aldehydes. The dicarbonyl compounds possess more ...

c&ndash;c bond cleavage: retro-aldol reaction

C&ndash;C Bond Cleavage: Retro-Aldol Reaction

The reverse of the aldol addition reaction is called the retro-aldol reaction. Here, the carbon&#8211;carbon bond in the aldol product is cleaved under ...

crossed aldol reactions: overview

Crossed Aldol Reactions: Overview

Crossed aldol addition is the reaction between two different carbonyl compounds under acidic or basic conditions. Here, both the carbonyl compounds ...

crossed aldol reaction using weak bases

Crossed Aldol Reaction Using Weak Bases

This lesson deals with the crossed aldol reaction using weak bases. The self-condensation of an aldehyde having &#945; hydrogen is prevented by adding it ...

ketones with nonenolizable aromatic aldehydes: claisen&ndash;schmidt condensation

ketones-with-nonenolizable-aromatic-aldehydes-claisenschmidt

Ketones with Nonenolizable Aromatic Aldehydes: Claisen&ndash;Schmidt Condensation

Benzaldehyde, like formaldehyde, lacks an &#945; hydrogen and cannot enolize to form an enolate. Hence, the reaction of benzaldehyde with a ketone in the ...

crossed aldol reaction using strong bases: directed aldol reaction

crossed-aldol-reaction-using-strong-bases-directed-aldol-reaction

Crossed Aldol Reaction Using Strong Bases: Directed Aldol Reaction

The reaction between two different carbonyl compounds comprising &#945; hydrogen in the presence of a strong base like lithium diisopropylamide (LDA) to ...

aldol condensation with &beta;-diesters: knoevenagel condensation

aldol-condensation-with-diesters-knoevenagel-condensation

Aldol Condensation with &beta;-Diesters: Knoevenagel Condensation

The Knoevenagel condensation is an aldol-type reaction involving the condensation of aldehydes or ketones with active methylene compounds such as ...

esters to &beta;-ketoesters: claisen condensation overview

esters-to-ketoesters-claisen-condensation-overview

Esters to &beta;-Ketoesters: Claisen Condensation Overview

Regular Claisen condensation is a base-promoted reaction involving identical esters with two &#945; hydrogens, condensing to produce &#946;-ketoesters. It ...

esters to &beta;-ketoesters: claisen condensation mechanism

esters-to-ketoesters-claisen-condensation-mechanism

Esters to &beta;-Ketoesters: Claisen Condensation Mechanism

Regular Claisen condensation involves the synthesis of &#946;-ketoesters by combining identical ester molecules bearing two &#945; hydrogens in the ...

aldol condensation vs claisen condensation

aldol-condensation-vs-claisen-condensation

Aldol Condensation vs Claisen Condensation

Aldol condensation is an acid&#160;or base-catalyzed condensation between aldehydes or ketones to give an &#945;,&#42933;-unsaturated carbonyl compound. A ...

intramolecular claisen condensation of dicarboxylic esters: dieckmann cyclization

intramolecular-claisen-condensation-dicarboxylic-esters-dieckmann

Intramolecular Claisen Condensation of Dicarboxylic Esters: Dieckmann Cyclization

Dieckmann cyclization is an intramolecular Claisen condensation of diesters. The reaction occurs in the presence of a base and generates a cyclic ...

&beta;-dicarbonyl compounds via crossed claisen condensations

-dicarbonyl-compounds-via-crossed-claisen-condensations

&beta;-Dicarbonyl Compounds via Crossed Claisen Condensations

Crossed Claisen condensations are base-promoted reactions between two different ester molecules producing &#946;-dicarbonyl compounds.&#160; The reaction ...

&alpha;-alkylation of ketones via enolate ions

&alpha;-Alkylation of Ketones via Enolate Ions

Ketones with &alpha; protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by ...

factors affecting &alpha;-alkylation of ketones: choice of base

factors-affecting-alkylation-of-ketones-choice-of-base

Factors Affecting &alpha;-Alkylation of Ketones: Choice of Base

&#945;-Alkylation of ketones is achieved in the presence of alkyl halides and a base. The reaction proceeds via the formation of an enolate ion followed ...

alkylation of &beta;-ketoester enolates: acetoacetic ester synthesis

alkylation-of-ketoester-enolates-acetoacetic-ester-synthesis

Alkylation of &beta;-Ketoester Enolates: Acetoacetic Ester Synthesis

Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and &beta;-keto esters. The reaction occurs in the presence of an alkoxide ...

alkylation of &beta;-diester enolates: malonic ester synthesis

alkylation-of-diester-enolates-malonic-ester-synthesis

Alkylation of &beta;-Diester Enolates: Malonic Ester Synthesis

Malonic ester synthesis is a method to obtain &#945; substituted carboxylic acids from &#42933;-diesters such as diethyl malonate and alkyl halides.

The ...

conjugate addition to &alpha;,&beta;-unsaturated carbonyl compounds

conjugate-addition-to-unsaturated-carbonyl-compounds

Conjugate Addition to &alpha;,&beta;-Unsaturated Carbonyl Compounds

&#945;,&#946;-Unsaturated carbonyl compounds are molecules bearing a carbonyl and alkene functionality in conjugation with each other. The conjugation in ...

conjugate addition (1,4-addition) vs direct addition (1,2-addition)

conjugate-addition-14-addition-vs-direct-addition-12-addition

Conjugate Addition (1,4-Addition) vs Direct Addition (1,2-Addition)

&#945;,&#946;-Unsaturated carbonyl compounds with two electrophilic sites, the carbonyl carbon, and the &#946; carbon, are susceptible to nucleophilic ...

conjugate addition of enolates: michael addition

conjugate-addition-of-enolates-michael-addition

Conjugate Addition of Enolates: Michael Addition

The attack of a nucleophile at the &#946; carbon of an &#945;,&#946;-unsaturated carbonyl compound is called conjugate addition. Conjugate addition ...

cyclohexenones via michael addition and aldol condensation: the robinson annulation

cyclohexenones-via-michael-addition-aldol-condensation-robinson

Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation

Robinson annulation is a base-catalyzed reaction for the synthesis of 2-cyclohexenone derivatives from 1,3-dicarbonyl donors (such as cyclic diketones, ...

synthesis of &alpha;-substituted carbonyl compounds: the stork enamine reaction

synthesis-of-substituted-carbonyl-compounds-the-stork-enamine-reaction

Synthesis of &alpha;-Substituted Carbonyl Compounds: The Stork Enamine Reaction

&#945;-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines ...

nonenolizable aldehydes to acids and alcohols: the cannizzaro reaction

nonenolizable-aldehydes-to-acids-and-alcohols-the-cannizzaro-reaction

Nonenolizable Aldehydes to Acids and Alcohols: The Cannizzaro Reaction

The Cannizzaro reaction is a base-promoted redox reaction producing a primary alcohol and a carboxylic acid from two molecules of a nonenolizable ...

key terms and concepts

2.7K Views. The method to achieve α-brominated carboxylic acids using a mixture of phosphorus tribromide and bromine is known as the Hell–Volhard–Zelinski reaction. The reaction is catalyzed by phosphorus tribromide, which can be used directly or produced in situ from red phosphorus and bromine. The mechanism comprises PBr3 catalyzed conversion of acid to acid bromide and hydrogen bromide. The acid bromide enolizes to its enol form in the presence of HBr. The nucleophilic enol attacks the b...

Video: α-Bromination of Carboxylic Acids: Hell–Volhard–Zelinski Reaction

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.

15.11 : α-Bromination of Carboxylic Acids: Hell–Volhard–Zelinski Reaction

15.11 : α-Bromination of Carboxylic Acids: Hell–Volhard–Zelinski Reaction

15.1 : Reactivity of Enols

15.2 : Reactivity of Enolate Ions

15.3 : Types of Enols and Enolates

15.4 : Enolate Mechanism Conventions

15.5 : Regioselective Formation of Enolates

15.6 : Stereochemical Effects of Enolization

15.7 : Acid-Catalyzed α-Halogenation of Aldehydes and Ketones

15.8 : Base-Promoted α-Halogenation of Aldehydes and Ketones

15.9 : Multiple Halogenation of Methyl Ketones: Haloform Reaction

15.10 : α-Halogenation of Carboxylic Acid Derivatives: Overview

15.12 : Reactions of α-Halocarbonyl Compounds: Nucleophilic Substitution

15.13 : Nitrosation of Enols

15.14 : C–C Bond Formation: Aldol Condensation Overview

15.15 : Base-Catalyzed Aldol Addition Reaction

15.11 : α-Bromination of Carboxylic Acids: Hell–Volhard–Zelinski Reaction

15.11 : &alpha;-Bromination of Carboxylic Acids: Hell&ndash;Volhard&ndash;Zelinski Reaction

15.1 : Reactivity of Enols

15.2 : Reactivity of Enolate Ions

15.3 : Types of Enols and Enolates

15.4 : Enolate Mechanism Conventions

15.5 : Regioselective Formation of Enolates

15.6 : Stereochemical Effects of Enolization

15.7 : Acid-Catalyzed &alpha;-Halogenation of Aldehydes and Ketones

15.8 : Base-Promoted &alpha;-Halogenation of Aldehydes and Ketones

15.9 : Multiple Halogenation of Methyl Ketones: Haloform Reaction

15.10 : &alpha;-Halogenation of Carboxylic Acid Derivatives: Overview

15.12 : Reactions of &alpha;-Halocarbonyl Compounds: Nucleophilic Substitution

15.13 : Nitrosation of Enols

15.14 : C&ndash;C Bond Formation: Aldol Condensation Overview

15.15 : Base-Catalyzed Aldol Addition Reaction

15.11 : α-Bromination of Carboxylic Acids: Hell–Volhard–Zelinski Reaction

15.7 : Acid-Catalyzed α-Halogenation of Aldehydes and Ketones

15.8 : Base-Promoted α-Halogenation of Aldehydes and Ketones

15.10 : α-Halogenation of Carboxylic Acid Derivatives: Overview

15.12 : Reactions of α-Halocarbonyl Compounds: Nucleophilic Substitution

15.14 : C–C Bond Formation: Aldol Condensation Overview