9. Alkynes: An Introduction to Organic Synthesis Why this chapter? We will use alkyne chemistry to begin looking at general strategies used in organic synthesis
Alkynes • Hydrocarbons that contain carbon-carbon triple bonds C≡C • 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
9.1 Naming Alkynes • The general formula for the alkynes is CnH2n-2, the same as for cycloalkenes. • The common name for the smallest alkyne, C2H2, is acetylene. • Common names of other alkynes are treated as its derivatives – for instance, the alkylacetylenes.
Naming Alkynes: IUPAC • The IUPAC rules for naming alkenes also apply to alkynes with the ending “-yne” replacing –ene. • A number indicates the position of the triple bond in the main chain.
Alkynes having the structure, RCCH are terminal, those with the structure RCCR’ are internal. • Substituents bearing a triple bond are alkynl groups: • -CCH is named ethynyl; • -CH2CCH is 2-propynyl (propargyl).
In IUPAC nomenclature, a hydrocarbon containing both a double and a triple bond is called an alkenyne. The chain is numbered starting at the end closest to either functional group. In the case of a tie, the double bond is given the lower number. Alkynes containing a hydroxyl group are named alkynols. In this case, the –OH takes precedence over both double and triple bonds in numbering the chain.
Solution: 2,5-Dimethyl-3-hexyne 3,3-Dimethyl-1-butyne 3,3-Dimethyl-4-octyne 3,3,6-Trimethyl-4-heptyne 2,4-Octadiene-6-yne 6-Isopropylcyclodecyne
9.2 Preparation of Alkynes: Elimination Reactions of Dihalides • Treatment of a 1,2-dihalidoalkane with KOH or NaOH produces a two-fold elimination of HX • Vicinal dihalides are available from addition of bromine or chlorine to an alkene • Intermediate is a vinyl halide
1. 2. 3. 5. 4. Which compound can most easily undergo elimination to give an alkyne? • 1 • 2 • 3 • 4 • 5
Electronic Structure of Alkynes • C≡C triple bond results from sp orbital on each C forming a sigma bond and unhybridizedpX and pyorbitals forming π bonds. • The remaining sp orbitals form bonds to other atoms at 180º to C-C triple bond. • The C≡C bond is shorter and stronger than single or double • Breaking a π bond in acetylene (HC≡CH) requires 318 kJ/mole (in ethylene it is 268 kJ/mole)
Properties and Bonding in the Alkynes • Alkynes are relatively nonpolar. • Corresponding alkynes, alkenes and alkanes have very similar boiling points. • Ethyne: sublimes at -84oC • Propyne: b.p. -23.2oC • 1-Butyne: b.p. 8.1oC • 2-Butyne: b.p. 27oC • Medium sized alkanes: distillable liquids • Alkynes polymerize easily, frequently with violence.
Ethyne is linear and has strong, short bonds. • The two carbons in ethyne are sp2 hybridized. • The bonds are diffuse and resemble a cylindrical cloud:
The strength of a C≡C triple bond is about 958 kcal mol-1 (229 kcal mol-1). As with alkenes, the strength of the bonds is much weaker than that of the δ bond which gives rise to much of the chemical reactivity of the alkynes. The CC bond length is 1.20 Å (C=C is 1.33 Å). The C-H bond lengths are also shorter than in ethene due to the larger degree of s character in the sp hybrid bonds (as compared to sp2).
Alkynes are high-energy compounds. • Alkynes often react with the release of considerable amounts of energy (prone to explosive decomposition). • Ethyne has a heat of combustion of 311 kcal mol-1 which is capable of generating a flame temperature >2500o C, sufficient for use in welding torches.
The heats of hydrogenation of alkyne isomers can be used to determine their relative stabilities: The greater relative stabililty of internal alkynes is due to hyperconjugation.
9.3 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
Electrophilic Addition Reactions of Alkynes • Addition of hydrogen halides forms haloalkenes and geminal dihaloalkanes. • In an analogous reaction with alkenes, hydrogen halides add across alkyne triple bonds. The stereochemistry of this reaction is typically anti, particularly when excess halide ion is used.
A second molecule of hydrogen halide may also add, following Markovnikov’s rule, producing a geminal dihaloalkane. Terminal alkynes also react with hydrogen halide, again following Mrakovnikov’s rule, although it is difficult to limit the reaction to a single molecule of hydrogen halide.
Addition of HX to Alkynes Involves VinylicCarbocations • Addition of H-X to alkyne should produce a vinylic carbocation intermediate • Secondary vinyl carbocations form less readily than 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
Anti-Markovnikov Additions to Triple Bonds • Radical addition of HBr gives 1-bromoalkenes. • In the presence of light or other radical initiators, HBr can add to an alkyne by a radical mechanism in an anti-Markovnikov fashion. Both syn and anti additions are observed.
Addition of Bromine and Chlorine • Initial addition gives trans intermediate • Product with excess reagent is tetrahalide • Halogenation takes place once or twice. • Halogenation of alkynes proceeds through an isolatable intermediate vicinal dihaloalkene, to the tetrahaloalkane. The two additions are anti.
1. 2. 3. 4. 5. What is the product of the following reaction? • 1 • 2 • 3 • 4 • 5
1. 2. 3. 4. 5. If propyne reacts with Br2/H2O following the patterns of electrophilic-addition mechanisms, which of the following is the expected product? • 1 • 2 • 3 • 4 • 5
9.4 Hydration of Alkynes • Addition of H-OH as in alkenes • Mercury (II) catalyzes Markovinikov oriented addition • Hydroboration-oxidation gives the non-Markovnikov product
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 • The immediate product is a vinylic alcohol, or enol, which spontaneously transforms to a ketone
Mechanism of Mercury(II)-Catalyzed Hydration of Alkynes • Addition of Hg(II) to alkyne gives a vinylic cation • Water adds and loses a proton • A proton from aqueous acid replaces Hg(II)
Keto-enolTautomerism • Isomeric compounds that can rapidily interconvert by the movement of a proton are called tautomers and the phenomenon is called tautomerism • 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
Mercuric ion-catalyzed hydration of alkynes furnishes ketones. • In a reaction catalyzed by mercuric ion, water can be added to alkynes to give enols, which then tautomerize to give ketones.
Hydration follows Markovnikov’s rule: Terminal alkynes give methyl ketones:
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 always gives the methyl ketone, which is useful
Examples: Symmetrical internal alkynes give a single carbonyl compound; Unsymmetrical systems give a mixture of products:
Hydroboration/Oxidation of Alkynes • BH3 (borane) adds to alkynes to give a vinylic borane • 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
Comparison of Hydration of Terminal Alkynes • The product from the mercury(II) catalyzed hydration converts terminal alkynes to methyl ketones • Hydroboration/oxidation converts terminal alkynes to aldehydes because addition of water is non-Markovnikov
Which is the best starting material to prepare 2-pentanone? • pentane • 1-pentene • 2-pentene • 1-pentyne • 2-pentyne
1. 2. 3. 4. 5. What is the structure of intermediate I? • 1 • 2 • 3 • 4 • 5
9.5 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
Example: Catalytic hydrogenation of alkynes using hydrogen and a platinum or palladium on charcoal catalyst results in complete saturation.
Conversion of Alkynes to cis-Alkenes • Addition of H2 using chemically deactivated palladium on calcium carbonate as a catalyst (the Lindlar catalyst) produces a cis alkene • The two hydrogens add syn (from the same side of the triple bond)
Catalytic hydrogenation using a Lindlar catalyst (palladium precipitated on CaCO3, and treated with lead acetate and quinoline) adds only one equivalent of hydrogen in a syn process: This method affords a stereoselective synthesis of cis alkenes from alkynes.
Examples: Used in the commercial synthesis of Vitamin A p. 268
Conversion of Alkynes to trans-Alkenes • Anhydrous ammonia (NH3) is a liquid below -33 ºC • Alkali metals (Li or Na) 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