9. Alkynes: An Introduction to Organic Synthesis

1. 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

2. 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

3. 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.

4. 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.

5. Alkynes having the structure, RCCH are terminal, those with the structure RCCR’ are internal. • Substituents bearing a triple bond are alkynl groups: • -CCH is named ethynyl; • -CH2CCH is 2-propynyl (propargyl).

6. Side chains

7. 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.

8. Examples:

9. Examples:

10. Learning Check:

11. 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

12. 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

14. Mechanism:

15. 1. 2. 3. 5. 4. Which compound can most easily undergo elimination to give an alkyne? • 1 • 2 • 3 • 4 • 5

16. 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)

17. 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.

18. 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:

19. 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 CC 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).

20. 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.

21. 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.

22. 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

23. 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.

24. 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.

25. 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

26. 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.

27. 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.

28. Example:

29. 1. 2. 3. 4. 5. What is the product of the following reaction? • 1 • 2 • 3 • 4 • 5

30. 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

31. 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

32. 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

33. 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)

34. 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

35. 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.

36. Hydration follows Markovnikov’s rule: Terminal alkynes give methyl ketones:

37. 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

38. Examples: Symmetrical internal alkynes give a single carbonyl compound; Unsymmetrical systems give a mixture of products:

39. 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

40. 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

41. Which is the best starting material to prepare 2-pentanone? • pentane • 1-pentene • 2-pentene • 1-pentyne • 2-pentyne

42. 1. 2. 3. 4. 5. What is the structure of intermediate I? • 1 • 2 • 3 • 4 • 5

43. 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

44. Example: Catalytic hydrogenation of alkynes using hydrogen and a platinum or palladium on charcoal catalyst results in complete saturation.

45. 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)

46. 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.

47. Examples: Used in the commercial synthesis of Vitamin A p. 268

48. 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

50. Another representation of the mechanism: