Understanding Alkynes: Introduction & Organic Synthesis

1. Chapter 4-3: Continue Alkynes: An Introduction to Organic Synthesis Based on: McMurry’s Organic Chemistry, 6th edition, Chapter 4

2. Alkynes

3. Alkynes • Hydrocarbons that contain carbon-carbon triple bonds • Our study of alkynes provides an introduction to organic synthesis, the preparation of organic molecules from simpler organic molecules

4. Alkynes • Acetylene, the simplest alkyne, is produced industrially from methane and steam at high temperature

5. Electronic Structure of Alkynes • The triple bond is shorter and stronger than single or double • Breaking a π bond in acetylene (HCCH) requires 318 kJ/mole (in ethylene it is 268 kJ/mole)

6. Electronic Structure of Alkynes • Carbon-carbon triple bond results from an sp orbital on each C forming a sigma bond and unhybridized pX and py orbitals forming a π bond • The remaining sp orbitals form bonds to other atoms at 180º (linear geometry) to the C-C triple bond.

7. Electronic Structure of Alkynes

8. Nomenclature IUPAC: alkyne common: alkyl acetylene - an internal alkyne - a terminal alkyne

9. Structure-Property Relationships Structure H–CC–H + 2H2  CH3CH3DH = -74.5 kcal/mol CH3CH2–CC–H DH = -69.9 kcal/mol CH3–CC–CH3DH = -65.1 kcal/mol  more substituted = more stable

10. 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 includes the triple bond

11. Diynes, Enynes, and Triynes • A compound with two triple bonds is a diyne • An enyne has a double bond and triple bond • A triyne has three triple bonds • Number from chain that ends nearest a double or triple bond – double bonds is preferred if both are present in the same relative position

12. Nomenclature • en-ynes • number closest to nearest multiple bond • if choice start at C=C • 1-heptene-6-yne

13. Diynes, Enynes, and Triynes Alkynes as substituents are called “alkynyl”

14. Nomenclature Priority: OH > CC = C=C  alkenynol Name the following compounds. 3-methyl-1-pentyn-3-ol (Z)-4-propyl-3-dodecen-6,8,10-triyn-2-ol 5-ethyl-5-hexen-1-yn-3-ol 2-methyl-1-penten-7-yne

15. Problem: IUPAC names?

16. Preparation of Alkynes:Elimination Reactions of Dihalides • Treatment of a 1,2 dihaloalkane with KOH or NaOH produces a two-fold elimination of HX • Vicinal dihalides are available from addition of bromine or chlorine to an alkene

17. Preparation of Alkynes: Elimination Reactions of Dihalides • Intermediate is a vinyl halide

18. 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

19. Reactions of Alkynes: Addition of HX and X2

20. Addition of Bromine and Chlorine • Initial addition gives trans intermediate • Product with excess reagent is tetrahalide

21. Addition of HX to Alkynes Involves Vinylic Carbocations • 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

22. Vinylic carbocations

23. Hydration of Alkynes • Addition of H-OH as in alkenes • Mercury (II) catalyzes Markovinikov oriented addition • Hydroboration-oxidation gives the non-Markovnikov product

24. Mercury(II)-Catalyzed Hydration of Alkynes • 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

25. Keto-enol Tautomerism • 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

26. Keto-enol Tautomerism

27. 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. • Hydration of a terminal always gives the methyl ketone

28. 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: anti-Markovnikov

29. Comparison of Hydration of Terminal Alkynes • Hydroboration/oxidation converts terminal alkynes to aldehydes because addition of water is non-Markovnikov

30. 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

31. Incomplete reduction: 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)

32. Lindlar Catalyst syn addition Lindlar is a special catalyst that allows the hydrogenation of an alkyne to stop after one mole of hydrogen is added. Most amines, and compounds containing sulfur, reduce the activity of catalysts or “poison” them. quinoline

34. 7-cis-Retinol synthesis (Hoffmann-LaRoche):

35. Incomplete reduction: Conversion of Alkynes to trans-Alkenes • Anhydrous ammonia (NH3) is a liquid below -33 ºC • Alkali metals dissolve in liquid ammonia and function as reducing agents • Alkynes are reduced to trans alkenes with sodium or lithium in liquid ammonia

37. Acidity • A major difference between the chemistry of alkynes and that of alkenes and alkanes is the acidityof the hydrogen bonded to a triply bonded carbon • The pKa of acetylene is approximately 25, which makes it a stronger acid than ammonia

38. Structure-Property Relationships Acidity of terminal alkynes Recall: acidity increases (electronegativity) CH4 NH3 H2O HF pKa ~60 ~36 ~16 ~3 but: increasing s character, electrons held more closely; carbon is more electronegative

39. Acidity

40. Acidity • Acetylene reacts with sodium amide to form sodium acetylide • It can also be converted to its metal salt by reaction with sodium hydride or lithium diisopropylamide (LDA)

41. Acidity • Water is a stronger acid than acetylene; hydroxide ion is not a strong enough base to convert acetylene to its anion

42. Alkyne Acidity: Formation of Acetylide Anions • Terminal alkynes are weak Brønsted acids (pKa ~ 25). • 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, stabilizing the anion.

44. Alkylation of Acetylide Anions • Acetylide ions can react as nucleophiles as well as bases

45. Alkylation of Acetylide Anions • The negative charge and unshared electron pair on carbon makes the acetylide anion strongly nucleophilic. Therefore, an acetylide anion can react with an alkyl halide to substitute for the halogen.

46. جایگزینی نوکلئوفیلی SN2: چهاروجهی مسطح چهاروجهی

47. Alkylation of Acetylide Anions جایگزینی نوکلئوفیلی SN2: حالت گذار Nucleophilic acetylide anion attacks the electrophilic carbon. As the new C-C bond begins to form, the C-Br bond begins to break in the transition state.

48. جایگزینی نوکلئوفیلی SN2:

49. Limitations of Alkyation of Acetylide Ions • Reactions only are efficient with 1º alkyl bromides and alkyl iodides • Reactions with 2º and 3º alkyl halides gives dehydrohalogenation, converting alkyl halide to alkene

50. جایگزینی نوکلئوفیلی SN1: 50% مخلوط راسمیک 50% 80% 20%