Name: alkyne chain extension by alkylation
Uploaded: 2025-05-22T09:05:34.000Z
Duration: 2 min 27 s
Channel: JoVE

One of the two main approaches to preparing alkynes involves alkylation of terminal alkynes to form longer carbon-chain alkynes.
The preparation of alkynes using the alkylation approach proceeds in two steps.
The first step is a deprotonation reaction where a terminal alkyne reacts with a strong base like sodium amide to form the acetylide ion.
The second step is a substitution reaction in which the acetylide ion reacts with a primary alkyl halide to yield a longer carbon&#8211;chain alkyne.
Since a new alkyl group gets added to the starting alkyne, the reaction is called an alkylation reaction.
Recall that an acetylide ion is a strong base and can function as a strong nucleophile.
The substitution reaction follows an SN2 mechanism in which the nucleophilic acetylide ion attacks the positively polarized carbon of the alkyl halide from a direction opposite to the halide leaving group.
This results in a transition state with a partially formed carbon&#8211;carbon bond and a partially broken carbon&#8211;halogen bond. The displacement of the leaving group yields the product with an inverted stereochemistry at the reaction center.
The SN2 reaction is most efficient with unhindered alkyl halides like methyl halide and other primary alkyl halides, which are less sterically hindered allowing for the simultaneous nucleophilic attack and departure of the leaving group.
In contrast, with the bulky secondary and tertiary alkyl halides, acetylide ions act as strong bases and undergo an E2 elimination instead of substitution.
Alkylation of terminal alkynes is a useful method to synthesize longer carbon-chain alkynes. For example, deprotonation of acetylene and subsequent reaction with methyl bromide yields 1-propyne. This terminal alkyne can be further deprotonated and made to react with a different alkyl halide, like ethyl bromide, to form an internal alkyne, 2-pentyne.

preparation of alkynes: alkylation reaction

Preparation of Alkynes: Alkylation Reaction

<h4>Introduction</h4>
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
<img alt="Organic synthesis reaction diagram; reactants acetylene and NaNH2; product alkylated alkyne." src="/files/ftp_upload/11834/11834_PT_Figure_1.svg" style="text-align: center; height: 50px;" data-altupdatedat="1754904545000" data-alt="Alkyne alkylation reaction using NaNH2 and ethyl bromide, chemical equation diagram." />
The reaction takes place in two steps:
1. The first step is the deprotonation of the terminal alkyne by the strong base forming an acetylide ion.
<img alt="Alkyne deprotonation using sodium amide; chemical equation; acid-base reaction mechanism." src="/files/ftp_upload/11834/11834_PT_Figure_2.svg" style="text-align: center; height: 50px;" data-altupdatedat="1754904545000" data-alt="Alkyne ionization reaction equation NaNH2, diagram shows acetylene converting to acetylide ion." />
2. The second step is a nucleophilic substitution reaction in which the acetylide ion reacts with the alkyl halide to form a new C&#8211;C bond.
<img alt="Alkyne synthesis equation, Na+ + Br- mechanism, chemical reaction diagram." src="/files/ftp_upload/11834/11834_PT_Figure_3.svg" style="text-align: center; height: 50px;" data-altupdatedat="1754904545000" data-alt="Organic reaction mechanism, Na+ and Br- ion exchange, illustrates chemical synthesis process." />
<h4>Reaction Mechanism &#8212;SN2 pathway </h4>
Acetylide ions are strong bases and can also function as good nucleophiles. The substitution reaction follows an SN2 pathway where the nucleophilic acetylide ion attacks the electrophilic carbon of the primary alkyl halide from the backside.
<img alt="Alkyne reaction mechanism diagram with Na+ and Br- ion interactions and transition state formation." src="/files/ftp_upload/11834/11834_PT_Figure_4.svg" style="text-align: center; height: 250px;" data-altupdatedat="1754904545000" data-alt="Nucleophilic substitution reaction mechanism diagram with alkynes, NaBr formation, chemical process." />
Since this is a concerted process, the nucleophilic attack and the departure of the leaving group takes place simultaneously to form the product with an inverted stereochemistry at the reaction center.
The reaction works best with unhindered alkyl halides like methyl halide and other primary halides. With secondary and tertiary alkyl halides, acetylide ions act as strong bases, in which case E2 elimination is the preferred pathway.
<h4>Application in organic synthesis </h4>
Alkylation of simple terminal alkynes is a useful method to extend the length of the carbon chain. Acetylene, a terminal alkyne, can be converted to a higher internal alkyne by repeated alkylation as shown below:
<img alt="Alkyne synthesis reaction sequence, organic chemistry, showing stepwise alkylation process, equation." src="/files/ftp_upload/11834/11834_PT_Figure_5.svg" style="text-align: center; height: 50px;" data-altupdatedat="1754904545000" data-alt="Alkyne chain elongation via NaNH&#8322;, CH&#8323;Br; reaction equation diagram for organic synthesis." />

Introduction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for ...

preparation-of-alkynes-alkylation-reaction

Education

JoVE Core

Organic Chemistry

Unit 1

Alkynes

KEY TERMS AND CONCEPTS

alkyne chain extension by alkylation

Terminal alkynes can be made into longer carbon-chain alkynes by alkylation with primary alkyl halides. This reaction uses a strong base such as sodium amide. One example is 1-propyne, which reacts with sodium amide and then ethyl bromide to give 2-pentyne.

The reaction happens in two steps. First, the strong base removes the acidic hydrogen from the terminal alkyne and forms an acetylide ion. An acetylide ion is the carbon-based species that then takes part in the next step.

Next, the acetylide ion reacts with the alkyl halide in a nucleophilic substitution reaction. It forms a new carbon-carbon bond, which is why this method is useful for building larger alkynes. The substitution follows an SN2 pathway, where the acetylide ion attacks from the backside and the leaving group leaves at the same time.

Because SN2 is a concerted process, the bond-making and bond-breaking happen together. This also gives inverted stereochemistry at the reaction center. The reaction works best with unhindered alkyl halides such as methyl halides and other primary halides.

Secondary and tertiary alkyl halides do not work as well in this reaction. In those cases, the acetylide ion behaves as a strong base, and E2 elimination is preferred. Repeated alkylation of acetylene can convert a simple terminal alkyne into a higher internal alkyne.

Alkyne Chain Extension by Alkylation

structure and physical properties of alkynes

structure-and-physical-properties-of-alkynes

Alkyne Bonds, Shape, and Physical Traits

Alkynes are hydrocarbons with carbon-carbon triple bonds. They are unsaturated compounds and are written with the general formula CnH2n-2. This group includes simple molecules like ethyne, also called acetylene, which is a colorless gas used as a fuel for welding because it burns at high temperatures. Alkynes also appear in natural and synthetic compounds. Some natural alkynes are found in the poison from South American tree frogs. Synthetic alkyne-containing compounds are found in medicines...

nomenclature of alkynes

Naming Alkynes with IUPAC Rules

Alkynes are unsaturated hydrocarbons with carbon-carbon triple bonds. Their general formula is CnH2n-2, and their names use the suffix "-yne" instead of "-ane" or "-ene." Alkynes can be named with IUPAC names or common names. The IUPAC system uses a step-by-step method based on the molecule’s structure. First, find the longest carbon chain that contains the triple bond. Add the suffix "-yne" to the parent chain name. In the example shown, the longest chain has seven carbon atoms, so the parent...

acidity of 1-alkynes

Why Terminal Alkynes Form Acetylide Ions

Terminal alkynes are more acidic than alkenes and alkanes. Acid strength is usually measured with pKa, and a lower pKa means a stronger acid. Ethane has a pKa of 51, ethene has a pKa of 44, and acetylene has a pKa of 25. That means acetylene is far more acidic than the other two hydrocarbons. This difference comes from the stability of the carbanion formed after deprotonation. A carbanion is a negatively charged carbon species. In ethane, ethene, and acetylene, the lone pair sits in an sp3,...

Terminal alkynes can be made into longer carbon-chain alkynes by alkylation with primary alkyl halides. This reaction uses a strong base such as sodium amide. One example is 1-propyne, which reacts with sodium amide and then ethyl bromide to give 2-pentyne. The reaction happens in two steps. First, the strong base removes the acidic hydrogen from the terminal alkyne and forms an acetylide ion. An acetylide ion is the carbon-based species that then takes part in the next step. Next, the...

preparation of alkynes: dehydrohalogenation

preparation-of-alkynes-dehydrohalogenation

Making Alkynes from Dihalides

Alkynes can be made from vicinal or geminal dihalides by dehydrohalogenation. This reaction uses a strong base, such as sodium amide, in liquid ammonia. Two equivalents of hydrogen halide are lost through two successive E2 elimination reactions. In a vicinal dihalide, the two halogen atoms are on neighboring carbon atoms. The first E2 step removes a proton that is anti to the leaving group. Because E2 reactions are concerted, the proton is removed and the halide leaves at the same time. This...

electrophilic addition to alkynes: halogenation

electrophilic-addition-to-alkynes-halogenation

Alkyne Halogenation and Anti Addition

Alkyne halogenation is an electrophilic addition reaction where a halogen molecule adds across a triple bond. Because alkynes have two π bonds, they can add two equivalents of bromine or chlorine. The first addition usually gives a trans-dihaloalkene as the major product and the cis isomer as the minor product. A second equivalent of halogen then forms the tetrahalide. The reaction begins when a π bond in the alkyne acts as a nucleophile and attacks the electrophilic end of the polarized...

electrophilic addition to alkynes: hydrohalogenation

electrophilic-addition-to-alkynes-hydrohalogenation

Alkyne Reactions with HX and HBr Peroxides

Hydrohalogenation of alkynes adds hydrogen halides, HX, across a carbon-carbon triple bond. In this reaction, X can be chlorine, bromine, or iodine. The first addition gives a vinyl halide, and the second addition gives a geminal dihalide. When HCl reacts with an alkyne, one pathway begins with proton transfer to the triple bond. The pi electrons attack the hydrogen in hydrogen chloride and push out chloride ion. This forms a secondary vinylic carbocation, and chloride then attacks to make a...

alkynes to aldehydes and ketones: acid-catalyzed hydration

alkynes-to-aldehydes-and-ketones-acid-catalyzed-hydration

Keto-Enol Tautomerism in Alkyne Hydration

Alkyne hydration uses acid, water, and a mercuric salt to convert alkynes into aldehydes and ketones. It is similar to alkene hydration, but the product type is different. A mercuric salt such as mercuric sulfate, HgSO4, is usually added because the reaction is much slower than alkene hydration. Terminal alkynes follow Markovnikov’s rule during hydration. In contrast, internal alkynes do not add water in a regioselective way. That means the product outcome depends on the alkynes structure. <br...

alkynes to aldehydes and ketones: hydroboration-oxidation

alkynes-to-aldehydes-and-ketones-hydroboration-oxidation

Alkyne Hydration via Borane and Peroxide

Alkyne hydration can make aldehydes and ketones through hydroboration-oxidation. In this indirect hydration reaction, an alkyne first reacts with borane, then with alkaline peroxide. The alkyne forms an enol, and that enol quickly changes into a carbonyl product. Terminal alkynes give aldehydes, while internal alkynes give ketones. The reaction happens in two steps. The hydroboration step is a concerted syn addition, which means the boron and hydrogen add to the same side of the carbon-carbon...

alkynes to carboxylic acids: oxidative cleavage

alkynes-to-carboxylic-acids-oxidative-cleavage

Triple-Bond Cleavage in Alkynes

Alkynes can be broken apart by oxidative cleavage. This reaction uses strong oxidizing reagents such as potassium permanganate and ozone. It cuts the triple bond, which has one sigma bond and two pi bonds, and turns the alkyne into carboxylic acids. With warm, basic aqueous potassium permanganate, the alkyne first forms an unstable alpha-diketone intermediate. The reaction then gives carboxylate salts. A mild acid treatment protonates these carboxylate anions and produces the free carboxylic...

reduction of alkynes to cis-alkenes: catalytic hydrogenation

reduction-of-alkynes-to-cis-alkenes-catalytic-hydrogenation

Stopping Alkyne Hydrogenation at cis-Alkenes

Alkyne hydrogenation can stop at a cis-alkene instead of going all the way to an alkane. Transition metal catalysts such as Pt, Pd, or Ni add hydrogen in two syn steps, which means both hydrogens add to the same side. The cis-alkene is the key intermediate in this process. Hydrogenation also helps compare the thermodynamic stability of hydrocarbons. Acetylene has a heat of hydrogenation of −176 kJ/mol, while ethylene has a value of −137 kJ/mol. The larger heat released for acetylene shows that...

reduction of alkynes to trans-alkenes: sodium in liquid ammonia

reduction-of-alkynes-to-trans-alkenes-sodium-in-liquid-ammonia

Dissolving Metal Reduction of Alkynes

Dissolving metal reduction turns alkynes into trans-alkenes with sodium or lithium in liquid ammonia. This reaction gives the alkene with anti addition across the carbon-carbon triple bond, which leads to the trans product. The reaction must be kept very cold because ammonia is a gas at room temperature. It is run with a dry ice and acetone bath, which holds the mixture at low temperature. When sodium dissolves in liquid ammonia, it forms sodium ions and free electrons. Ammonia molecules...

key terms and concepts

Learn how terminal alkynes are extended with primary alkyl halides using sodium amide, forming acetylide ions and new carbon-carbon bonds through SN2.

Alkyne Chain Extension by Alkylation | JoVE K12

organic chemistry

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Alkyne Chain Extension by Alkylation

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