Name: alkyl halide reduction with tributyltin hydride
Uploaded: 2023-04-30T11:22:27.000Z
Duration: 1 min 26 s
Channel: JoVE

Las reacciones de sustitución radical son útiles para la halogenación de alcanos y alquenos.
Del mismo modo, las sustituciones de radicales pueden eliminar el halógeno de los haluros de alquilo utilizando hidruro de tributilo de estaño, lo que se conoce como hidrogenólisis de haluros de alquilo.
En particular, el hidruro de estaño tiene un enlace Sn-H débil y puede reaccionar con haluros de alquilo para reemplazar el halógeno con hidrógeno, formando alcano y haluro de estaño.
La reacción se ve favorecida energéticamente ya que los nuevos enlaces formados son más fuertes que los enlaces rotos.
El mecanismo de la hidrogenólisis sigue una reacción en cadena.
Inicialmente, el hidruro de estaño produce un radical tributilo de estaño en presencia de luz, que luego abstrae el halógeno de un haluro orgánico produciendo un radical intermedio.
A continuación, el radical intermedio extrae el hidrógeno del hidruro de estaño para formar finalmente un alcano y un radical tributilo de estaño, que propaga la reacción. 
La reactividad de los haluros de alquilo hacia la hidrogenólisis disminuye de yoduro a fluoruro, donde los fluoruros de alquilo no son reactivos.
En particular, la reducción de los cloruros de alquilo requiere una mayor concentración de radicales tributilo de estaño, lo que se logra agregando un iniciador como AIBN a la reacción.

sustitución radical: hidrogenólisis de haluros de alquilo con hidruro de tributilestaño

Radical Substitution: Hydrogenolysis of Alkyl Halides with Tributyltin Hydride

Las reacciones de sustitución radical se pueden utilizar para eliminar grupos funcionales de las moléculas. La hidrogenólisis de haluros de alquilo es una de esas reacciones, en la que el enlace débil Sn-H en el hidruro de tributilestaño reacciona con haluros de alquilo para formar alcanos. En este caso, el reactivo Bu_3SnH produce haluro de tributilestaño como subproducto.


 Los enlaces formados en esta reacción son más fuertes que los enlaces rotos, lo que la hace energéticamente favorable. La reacción sigue un mecanismo de cadena radical similar a las reacciones de halogenación radical, donde Bu_3SnH sufre escisión homolítica en presencia de luz para formar un radical tributilestaño. Este radical extrae el halógeno de un haluro de alquilo, formando un radical alquilo intermedio y un haluro de tributilestaño. El radical intermedio extrae aún más hidrógeno del hidruro de tributilestaño y produce un alcano y un radical tributilestaño, que propaga la reacción.


 Como los enlaces C-Br y C-I son más débiles que los enlaces C-Cl, la luz del día es suficiente para iniciar la hidrogenólisis de bromuros y yoduros de alquilo. Por el contrario, los fluoruros de alquilo no son reactivos debido a los fuertes enlaces C-F. La hidrogenólisis de cloruros de alquilo utilizando Bu_3SnH requiere una alta concentración de radicales tributilestaño, lo que se logra añadiendo un iniciador a la mezcla de reacción. AIBN es el iniciador más utilizado, ya que sufre homólisis térmica por encima de 60 °C para formar radicales estabilizados con nitrilo. Estos radicales extraen hidrógeno del hidruro de tributilestaño, formando el radical tributilestaño, que propaga la reacción.

<img alt="Figure1" src="/files/ftp_upload/12901/PT_12901_Figure%201.svg" style="text-align: center; height: 190px;">

 Los peróxidos no se utilizan como iniciadores porque los radicales peróxido son altamente reactivos y pueden extraer hidrógeno de los haluros orgánicos, lo que provoca reacciones secundarias no deseadas.

Sustitución radical: hidrogenólisis de haluros de alquilo con hidruro de tributilestaño

Las reacciones de sustitución radical se pueden utilizar para eliminar grupos funcionales de las moléculas. La hidrogenólisis de haluros de alquilo es una de esas reacciones, en la que el ...

radical-substitution-hydrogenolysis-alkyl-halides-with-tributyltin

Education

Educación

JoVE Core

Organic Chemistry

Química Orgánica

Unit 1

Unidad 1

Radical Chemistry

Química de radicales

KEY TERMS AND CONCEPTS

TÉRMINOS Y CONCEPTOS CLAVE

alkyl halide reduction with tributyltin hydride

Alkyl halide reduction with tributyltin hydride removes a halogen and replaces it with hydrogen. This reaction turns alkyl halides into alkanes. The reagent Bu3SnH has a weak Sn–H bond, and the reaction forms tributyltin halide as a byproduct. Because the new bonds are stronger than the bonds that are broken, the reaction is energetically favorable.

The reaction proceeds by a radical chain mechanism, which is similar to radical halogenation. Light causes Bu3SnH to split homolytically, meaning the bond breaks evenly to form a tributyltin radical. That radical removes the halogen from the alkyl halide. This step creates an alkyl radical intermediate and tributyltin halide.

Next, the alkyl radical takes hydrogen from tributyltin hydride. This forms the alkane product and a new tributyltin radical. The new radical then continues the chain reaction.

Bond strength affects how easily the reaction starts. C–Br and C–I bonds are weaker than C–Cl bonds, so daylight can start the hydrogenolysis of alkyl bromides and iodides. Alkyl fluorides do not react because C–F bonds are very strong.

Alkyl chlorides need more tributyltin radicals, so an initiator is added to the reaction mixture. AIBN is the most common initiator. Above 60 °C, it undergoes thermal homolysis and forms nitrile-stabilized radicals. These radicals remove hydrogen from tributyltin hydride and create the tributyltin radical that keeps the reaction going.

Peroxides are not used as initiators in this reaction. Their radicals are very reactive and can remove hydrogen from organic halides. That can lead to unwanted side reactions.

Alkyl Halide Reduction with Tributyltin Hydride

alkyl-halide-reduction-with-tributyltin-hydride

radicals: electronic structure and geometry

radicals-electronic-structure-and-geometry

Radical Geometry: Planarity and Inversion

Radical geometry depends on the electronic structure around the radical center. An unpaired electron, like a lone pair, affects the shape of the molecule. For a trivalent radical, the structure falls between the geometries of carbocations and carbanions. A carbocation with sp2 hybridization is trigonal planar. A carbanion with sp3 hybridization is trigonal pyramidal. The difference comes from the number of nonbonding electrons. The carbocation has none, while the carbanion has two. A carbon...

electron paramagnetic resonance (epr) spectroscopy: organic radicals

electron-paramagnetic-resonance-epr-spectroscopy-organic-radicals

EPR Hyperfine Splitting in Organic Radicals

Electron paramagnetic resonance (EPR) spectroscopy can show how an unpaired electron behaves in an organic radical. A simple radical may give a single peak because the electron moves between two spin energy states. In many radicals, the unpaired electron also interacts with nearby spin-active nuclei. This interaction is called hyperfine coupling. It causes hyperfine splitting, which divides the EPR signal into multiplets, or groups of peaks. The number of peaks follows the pattern 2nI + 1,...

radical formation: overview

How Radicals Are Generated

Radicals are generated when bonds break in specific ways or when one radical leads to another. In homolytic bond cleavage, a bond splits evenly and forms radicals. In heterolytic bond cleavage, the bond breaks to form ions instead. A fishhook arrow shows the movement of a single electron during homolytic cleavage. Radicals can come from spin-paired molecules by homolysis or by electron transfer. Homolysis forms two radicals. Electron transfer adds an electron to the molecule, and this process...

radical formation: homolysis

Homolysis and Radical Bonds

Homolysis is a bond-breaking process that splits a shared electron pair evenly. When a bond is broken with enough energy, the two electrons can also move to one atom in heterolysis, which forms ions. Homolysis gives one electron to each atom and creates radicals, which are highly reactive particles with an unpaired electron. HCl shows the difference between these bond cleavages. In solution, HCl can break into H+ and Cl− ions, and chlorine takes both bonding electrons, leaving a naked proton.

radical formation: abstraction

Radical Abstraction in Chain Reactions

Radical abstraction helps drive radical chain reactions. In this process, a relatively unstable radical removes an atom from a compound and forms a new radical that is more stable. The atom taken in this step can be hydrogen or a halogen. A radical initiator can first form radicals by homolysis, which is the breaking of a spin-paired molecule into two radicals. That is different from abstraction. In abstraction, a radical reacts with a spin-paired molecule and produces one new radical plus one...

radical formation: addition

Radical Addition and Spin Conservation

Radical addition can form a new radical when an unpaired electron adds to a spin-paired molecule. This is often seen with unsaturated species. In these reactions, the radical adds across a pi bond and breaks that bond to make a new radical. A bromine radical adding to an alkene is a clear example. The product is a carbon-centered radical. Radical reactions also follow spin conservation, much like chemical reactions follow charge conservation. If the starting material has an unpaired electron,...

radical formation: elimination

Radicals from Elimination Reactions

Radicals can form through elimination reactions. This route is the opposite of the addition route. It is driven by the instability of the radical. Dibenzoyl peroxide is one example of this process. It first undergoes homolysis, which is an even split of a bond, to give a pair of unstable radicals. Because the radical is unstable, it then undergoes elimination on its own. During elimination, a C-C bond breaks. The cleavage occurs between the alpha and beta positions relative to the radical...

radical reactivity: overview

Radical Reaction Pathways and Stability

Radical reactions follow a small set of pathways that help highly reactive species become more stable. A radical can react with another radical, with a spin-paired molecule, or through unimolecular decomposition, which means one radical species breaks down on its own. In radical-radical coupling, two radicals join to form a spin-paired molecule. In a radical reaction with a spin-paired molecule, a new radical and a new spin-paired molecule are formed. In radical decomposition, one radical...

radical reactivity: steric effects

Steric Shielding in Stable Radicals

Steric shielding helps make some radicals more stable and less reactive. A radical is a species with an unpaired electron at its center. In many cases, nearby groups can also give electronic stabilization, including electron-donating, electron-withdrawing, or conjugating groups. Several radicals are known as persistent radicals because they are remarkably stable. Examples include triphenylmethyl, tetramethylpiperidine-N-oxide, and 2,2-diphenyl-1-picrylhydrazyl. Some of these persistent...

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How Concentration Steers Radical Additions

Radical reaction selectivity can change when the concentrations of the reactants change. In this chemistry example, an alkyl halide reacts with an alkene in the presence of tin hydride and AIBN, an initiator that helps start the radical process. The reaction begins when a tin radical is formed. The tin radical removes the halogen from the alkyl halide. This step creates an alkyl radical. That radical then has two possible paths. It can react with tin hydride to form an alkane, or it can add to...

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radical-reactivity-electrophilic-radicals

Electrophilic Radicals and Alkene Reactions

Electrophilic radicals are radicals next to electron-withdrawing groups. These radicals react readily with nucleophilic alkenes. A key example is the malonate radical, where the radical center is flanked by two electron-withdrawing groups. It reacts easily with butyl vinyl ether, which has an electron-donating oxygen substituent. This reaction is favored because the malonate radical has a low-energy SOMO, or singly occupied molecular orbital. That low-energy orbital matches best with the...

radical reactivity: nucleophilic radicals

Nucleophilic Radicals and Alkene Traps

Nucleophilic radicals are electron-rich radicals that form next to electron-donating groups. They react readily with electrophilic alkenes, which are electron-poor double bonds. The key driving force is a SOMO–LUMO interaction. The high-energy SOMO, or singly occupied molecular orbital, of the radical overlaps with the low-energy LUMO of the alkene. These SOMO–LUMO interactions also explain radical traps and their effect on reaction selectivity. In radical chemistry, a trap is a molecule that...

radical reactivity: intramolecular vs intermolecular

radical-reactivity-intramolecular-vs-intermolecular

Radical Cyclization in One Molecule

Radical reactions can happen either between two separate molecules or within one molecule. In an intermolecular radical reaction, a nucleophilic radical adds to an electrophilic alkene, or an electrophilic radical adds to a nucleophilic alkene. The alkene is the radical trap, and it is a different molecule from the radical. Intermolecular reactions need the radical trap to be active and present in excess. They also usually require the radical starting material to contain a weak carbon-halogen...

radical autoxidation

Autoxidation in Oils and Ethers

Autoxidation is the oxidation of an organic compound in the presence of air or oxygen. In this process, compounds such as cumene can react with oxygen to form hydroperoxide. The reaction follows three main stages: initiation, propagation, and termination. Many organic compounds can undergo autoxidation. Ethers are especially vulnerable when oxygen is present, and they can form hydroperoxides. Even though this reaction is slow, old ether bottles may contain small amounts of peroxide. That is...

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radical-oxidation-of-allylic-and-benzylic-alcohols

Selective MnO2 Oxidation of Alcohols

Activated manganese(IV) oxide, or MnO2, is a selective oxidizing agent for allylic and benzylic alcohols. It changes primary allylic alcohols into aldehydes and secondary allylic alcohols into ketones. The reaction happens by a radical pathway, so the carbon next to the alcohol group plays a key role. The oxidizing agent is made from the redox reaction of potassium permanganate with an Mn(II) salt such as manganese sulfate. This can be done under alkaline or acidic conditions. After that, the...

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radical-substitution-halogenation-of-alkanes-and-alkyl-substituents

How Alkanes Form Alkyl Halides by Halogenation

Alkanes can react with halogens to form alkyl halides when heat or light is present. This reaction is called radical halogenation. It is a substitution reaction, which means a hydrogen atom on the alkane is replaced by a halogen atom. Radical chlorination of methane shows the process clearly. The reaction begins with initiation, when a chlorine molecule splits evenly under light or heat. This homolytic cleavage forms two very reactive chlorine radicals. The next stage is propagation. In the...

radical halogenation: thermodynamics

Alkane Halogenation: Stability and Reaction Rates

Alkane halogenation is shaped by thermodynamic stability and reaction rate. In radical halogenation, the key question is whether the reaction is favorable and how fast it happens. Gibbs free energy, or ΔG, helps answer the first question. ΔG has two parts: enthalpy, or ΔH, and entropy, or ΔS. For alkane halogenation, the entropy term is negligible because the number of reactant and product molecules is the same. That means ΔG is controlled mainly by enthalpy. Bond strength is the most...

radical halogenation: stereochemistry

Radical Halogenation: Chiral Products

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radical substitution: allylic chlorination

radical-substitution-allylic-chlorination

Allylic Chlorination by Radical Chain Reaction

Allylic chlorination is a radical chain reaction in alkenes. It happens when halogen reactions move away from simple addition and toward substitution at the allylic position, which is the carbon next to a double bond. At low temperatures, alkenes usually react with halogens by addition. When the temperature increases, or when the reaction conditions create radicals, allylic substitution becomes favored. This works because allylic hydrogens are very reactive and the intermediate formed is...

radical substitution: allylic bromination

Allylic Bromination with NBS

Allylic bromination with NBS changes propene into allyl bromide under radical conditions. In this reaction, the goal is to favor substitution at the allylic position instead of bromine addition across the double bond. Using N-bromosuccinimide, or NBS, helps keep the bromine concentration low so the addition product is less likely to form. The reaction conditions matter. Propene gives a dibromo addition product with bromine at room temperature. In non-polar solvents at high temperature, propene...

radical substitution: hydrogenolysis of alkyl halides with tributyltin hydride

Alkyl halide reduction with tributyltin hydride removes a halogen and replaces it with hydrogen. This reaction turns alkyl halides into alkanes. The reagent Bu3SnH has a weak Sn–H bond, and the reaction forms tributyltin halide as a byproduct. Because the new bonds are stronger than the bonds that are broken, the reaction is energetically favorable. The reaction proceeds by a radical chain mechanism, which is similar to radical halogenation. Light causes Bu3SnH to split homolytically, meaning...

radical anti-markovnikov addition to alkenes: overview

radical-anti-markovnikov-addition-to-alkenes-overview

Peroxide Effect in HBr Addition to Alkenes

Hydrogen bromide can add to alkenes through a peroxide-driven radical pathway. In this reaction, hydroperoxides or peroxides change the usual addition pattern and lead to alkyl bromides with anti-Markovnikov regiochemistry, which means bromine ends up on the less substituted carbon. This regioselectivity can be explained by radical stability. When the bromine radical adds to the alkene at the less substituted carbon, the reaction forms a more stable tertiary radical intermediate. The same...

radical anti-markovnikov addition to alkenes: mechanism

radical-anti-markovnikov-addition-to-alkenes-mechanism

Hydrogen Bromide Addition to Alkenes by Radicals

Hydrogen bromide can add to alkenes through a radical chain reaction when hydroperoxides or peroxides are present. This pathway gives anti-Markovnikov addition, which means the bromine ends up on the less substituted side of the double bond. The reaction begins with chain initiation. First, mild heating breaks the weak peroxide bond by homolytic cleavage, which means each atom keeps one electron and two alkoxy radicals form. Next, an alkoxy radical abstracts a hydrogen atom and forms a bromine...

radical anti-markovnikov addition to alkenes: thermodynamics

radical-anti-markovnikov-addition-to-alkenes-thermodynamics

HBr Selectivity in Alkene Addition Thermodynamics

Anti-Markovnikov addition of hydrogen halides to alkenes depends on thermodynamics. In this radical reaction, only HBr makes the overall process feasible. With HCl and HI, the same addition is thermodynamically unfavorable. Temperature affects whether the reaction is spontaneous. Spontaneity is measured with Gibbs free energy, or ΔG. When ΔG is negative, the reaction can occur on its own. ΔG is determined by two terms: ΔH, which is the enthalpy change, and −TΔS, which is the entropy term. The...

vicinal diols via reductive coupling of aldehydes or ketones: pinacol coupling overview

vicinal-diols-via-reductive-coupling-aldehydes-or-ketones-pinacol

Pinacol Coupling and Solvent Effects

Pinacol coupling is a radical dimerization reaction that joins aldehydes or ketones to form vicinal diols. Wilhelm Rudolph Fittig first discovered this reaction in 1859. It is a reductive coupling, which means the molecules are joined after they gain electrons. The reaction begins with a single electron transfer from metals such as sodium or magnesium to an aldehyde or ketone. This forms a ketyl, a radical anion. In a ketyl, the carbon atom can carry radical character while the oxygen atom...

alkenes via reductive coupling of aldehydes or ketones: mcmurry reaction

alkenes-via-reductive-coupling-aldehydes-or-ketones-mcmurry

Titanium-Coupled Alkenes from Carbonyls

The McMurry reaction turns aldehydes or ketones into alkenes with titanium metal. It first forms a diol-like intermediate through a coupling step, and then removes oxygen to make the double bond. In some cases, this process can be compared to pinacol coupling, which also joins carbonyl compounds. Titanium acts as a source of electrons in the first step. It transfers a single electron to the carbonyl group and forms a ketyl intermediate. That intermediate can lead to a vicinal diol, which is a...

&alpha;-hydroxy ketones via reductive coupling of esters: acyloin condensation overview

hydroxy-ketones-via-reductive-coupling-esters-acyloin-condensation

Acyloin Condensation: Ester Coupling Pathway

Acyloin condensation is a reaction that joins two ester molecules to form an alpha-hydroxy ketone. The product is also called an acyloin. In this reaction, sodium metal is used in an aprotic solvent, which supports the reductive coupling step. The reaction is related to the pinacol and McMurry reactions, which also involve reductive coupling of ketones or aldehydes. Here, the ester first becomes a ketyl. These ketyl species undergo radical dimerization and form an unstable tetrahedral...

key terms and concepts

Learn how tributyltin hydride removes halogens from alkyl halides through a radical chain reaction, and why light, AIBN, and bond strength matter.

Alkyl Halide Reduction with Tributyltin Hydride | JoVE K12

organic chemistry

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Alkyl Halide Reduction with Tributyltin Hydride

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