8.

Alkynes: An Introduction to Organic Synthesis

Based on McMurrys Organic Chemistry, 7th edition

Alkynes
Hydrocarbons that contain carbon-carbon

triple bonds Acetylene, the simplest alkyne is produced industrially from methane and steam at high temperature Our study of alkynes provides an introduction to organic synthesis, the preparation of organic molecules from simpler organic molecules

Why this chapter?

We will use alkyne chemistry to begin looking

at general strategies used in organic synthesis

8.1 Naming Alkynes

General hydrocarbon rules apply with -yne as a suffix

indicating an alkyne Numbering of chain with triple bond is set so that the smallest number possible for the first carbon of the triple bond Multiple triple bonds are: diynes, triynes, etc Double and triple bonds are: enynes Number nearest a multiple bond (either double or triple) If you have a choice, double bond lower number than triple

8.2 Preparation of Alkynes: Elimination Reactions of Dihalides

Treatment of a 1,2-dihalidoalkane with KOH or NaOH produces a two-fold

elimination of HX (double dehydrohalogenation) Vicinal dihalides are available from addition of bromine or chlorine to an alkene Intermediate is a vinyl halide (vinyl substituent = one attached to C=C)

8.3 Reactions of Alkynes: Addition of HX and X2

Addition reactions of alkynes are similar to

those of alkenes Intermediate alkene reacts further with excess reagent Regiospecificity according to Markovnikov

Electronic Structure of Alkynes

Carbon-carbon triple bond results from sp orbital on

each C forming a sigma bond and unhybridized pX and py orbitals forming bonds. The remaining sp orbitals form bonds to other atoms at 180 to C-C triple bond. The bond is shorter and stronger than single or double Breaking a bond in acetylene (HCCH) requires 318 kJ/mole (in ethylene it is 268 kJ/mole)

Addition of Bromine and Chlorine

Initial addition usually gives trans intermediate Can often be stopped at this stage if desired (1 eq. Br2) Product with excess reagent is tetrahalide

Addition of HX to Alkynes Involves Vinylic Carbocations

Addition of H-X to alkyne

should produce a vinylic carbocation intermediate Secondary vinyl carbocations are about as stable as primary alkyl carbocations Primary vinyl carbocations probably do not form at all Nonethelss, H-Br can add to an alkyne to give a vinyl bromide if the Br is not on a primary carbon
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8.4 Hydration of Alkynes

Addition of H-OH as in alkenes Mercury (II) catalyzes Markovnikov oriented addition Hydroboration-oxidation gives the non-Markovnikov product

Keto-enol Tautomerism Tautomerism = Isomeric compounds that rapidily interconvert by the movement of a proton and are called tautomers Enols rearrange to the isomeric ketone by the rapid transfer of a proton from the hydroxyl to the alkene carbon The keto form is usually so stable compared to the enol that only the keto form can be observed

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Mercury(II)-Catalyzed Hydration of Alkynes

Alkynes do not react with aqueous protic acids
Mercuric ion (as the sulfate) is a Lewis acid catalyst

that promotes addition of water in Markovnikov orientation

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Mechanism of Mercury(II)-Catalyzed Hydration of Alkynes

The immediate product is a vinylic alcohol, or enol, which spontaneously

transforms to a ketone

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Hydration of Unsymmetrical Alkynes

If the alkyl groups at either end of the C-C triple bond

are not the same, both products can form and this is not normally useful If the triple bond is at the first carbon of the chain (then H is what is attached to one side) this is called a terminal alkyne Hydration of a terminal alkyne always gives the methyl ketone, which is useful

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Hydroboration/Oxidation of Alkynes
BH3 (borane) adds to alkynes to give a vinylic borane Anti-Markovnikov Oxidation with H2O2 produces an enol that converts to the

ketone or aldehyde Process converts alkyne to ketone or aldehyde with orientation opposite to mercuric ion catalyzed hydration

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Comparison of Hydration of Terminal Alkynes

Unhindered terminal alkynes add two boranes Hydroboration/oxidation converts terminal alkynes to aldehydes

because addition of water is non-Markovnikov

The product from the mercury(II) catalyzed hydration converts

terminal alkynes to methyl ketones

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8.5 Reduction of Alkynes

Addition of H2 over a metal catalyst (such as

palladium on carbon, Pd/C) converts alkynes to alkanes (complete reduction) The addition of the first equivalent of H2 produces an alkene, which is more reactive than the alkyne so the alkene is not observed

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 Addition of H2 using chemically deactivated palladium on calcium

Conversion of Alkynes to cis-Alkenes

carbonate as a catalyst (the Lindlar catalyst) produces a cis alkene

The two hydrogens add syn (from the same side of the triple bond) The Lindlar Catalyst will not reduce double bonds

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Conversion of Alkynes to trans-Alkenes

Anhydrous ammonia (NH3) is a liquid below -33 C Alkali metals dissolve in liquid ammonia and function as reducing agents Alkynes are reduced to trans alkenes with sodium or

lithium in liquid ammonia The reaction involves a radical anion intermediate

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The trans stereochemistry is less sterically crowded and is formed in this step

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8.6 Oxidative Cleavage of Alkynes

Strong oxidizing reagents (O3 or KMnO4) cleave internal

alkynes, producing two carboxylic acids Terminal alkynes are oxidized to a carboxylic acid and carbon dioxide Neither process is useful in modern synthesis were used to elucidate structures because the products indicate the structure of the alkyne precursor

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Alkyne Acidity: Formation of Acetylide Anions

Terminal alkynes are weak Brnsted acids (alkenes and alkanes are much

less acidic (pKa ~ 25. See Table 8.1 for comparisons)) Reaction of strong anhydrous bases with a terminal acetylene produces an acetylide ion The sp-hydbridization at carbon holds negative charge relatively close to the positive nucleus

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8.8 Alkylation of Acetylide Anions

Acetylide ions can react as nucleophiles as well as bases

(see Figure 8-6 for mechanism)

Reaction with a primary alkyl halide produces a hydrocarbon

that contains carbons from both partners, providing a general route to larger alkynes

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Limitations of Alkyation of Acetylide Ions

Reactions only are efficient with 1 alkyl bromides and alkyl iodides Acetylide anions can behave as bases as well as nucelophiles Reactions with 2 and 3 alkyl halides gives dehydrohalogenation,

converting alkyl halide to alkene

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8.9 An Introduction to Organic Synthesis

Organic synthesis creates molecules by design

Synthesis can produce new molecules that are

needed as drugs or materials Syntheses can be designed and tested to improve efficiency and safety for making known molecules Highly advanced synthesis is used to test ideas and methods, answering challenges Chemists who engage in synthesis may see some work as elegant or beautiful when it uses novel ideas or combinations of steps this is very subjective and not part of an introductory course
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Synthesis as a Tool for Learning Organic Chemistry

In order to propose a synthesis you must be familiar

with reactions

What they begin with What they lead to How they are accomplished What the limitations are

A synthesis combines a series of proposed steps to

go from a defined set of reactants to a specified product

Questions related to synthesis can include partial information about a reaction of series that the student completes

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Strategies for Synthesis

Compare the target and the starting material Consider reactions that efficiently produce the

outcome. Look at the product and think of what can lead to it Example

Problem: prepare octane from 1-pentyne Strategy: use acetylide coupling

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