1. An Introduction to Organic Synthesis
Chapter 8
Alkynes:
An Introduction to Organic Synthesis

2. Introduction
An alkyne is a hydrocarbon that contains a carbon-carbon triple bond

3. Acetylene is the simplest alkyne.
It is produced industrially from methane by high temperature decomposition (pyrolysis)
It is the starting material of many organic molecules

4. I. Alkynes: An Overview
Electronic Structure
Naming Alkynes

5. A. Electronic Structure
Carbon-carbon triple bond results from:
sp hybrid orbital on each C forming a s bond and
unhybridized py and pz orbitals forming a p bond

6. The remaining sp orbitals form bonds to other atoms at 180º to C-C triple bond.
The triple bond is shorter and stronger than single or double bond

7. The triple bond is shorter and stronger than single or double bond
Breaking a p bond in acetylene (HCCH) requires 318 kJ/mole (in ethylene it is 268 kJ/mole)

8. B. Naming Alkynes
Like alkanes and alkenes, alkynes are named according to the system devised by the International Union of Pure and Applied Chemistry (IUPAC).

9. Steps to naming alkynes1
Find the longest continuous carbon chain containing the triple bond
Name using the suffix –yne to indicate an alkyne.
The position of the triple bond is indicated by giving the number of the first alkyne carbon
Numbering of chain with triple bond is set so that the smallest number possible includes the triple bond
IE – is the energy required to remove an electron from an atom or ion in the gas phase
Atom in ground state (g) + energy  Atom+ (g) + e- Change in energy = ionization energy
EA – is the energy involved when a gaseous atom absorbs an electron to form a negative ion of the element. Atom (g) + e-  Atom- Change in Energy = EA

10. Steps to naming alkynes2
If more than one triple bond is present:
Indicate the position of each and use the suffixes -diyne, -triyne, …
A compound with two triple bonds is a diyne
A triyne has three triple bonds
IE – is the energy required to remove an electron from an atom or ion in the gas phase
Atom in ground state (g) + energy  Atom+ (g) + e- Change in energy = ionization energy
EA – is the energy involved when a gaseous atom absorbs an electron to form a negative ion of the element. Atom (g) + e-  Atom- Change in Energy = EA

11. Steps to naming alkynes3
If a triple and a double bond are present:
Name the compound an enyne
An enyne has a double bond and triple bond
Number from chain that ends nearest a double or triple bond - double bond is preferred if both are present in the same relative position
IE – is the energy required to remove an electron from an atom or ion in the gas phase
Atom in ground state (g) + energy  Atom+ (g) + e- Change in energy = ionization energy
EA – is the energy involved when a gaseous atom absorbs an electron to form a negative ion of the element. Atom (g) + e-  Atom- Change in Energy = EA

12. Alkynes as substituents are called “alkynyl”

13. Practice Problem: Name the following compounds:

14. Practice Problem: There are seven isomeric alkynes with the
Practice Problem: There are seven isomeric alkynes with the formula C6H10. Draw and name them

15. II. Synthesis of Alkynes
Elimination Reactions of Dihalides
Alkylation of Acetylide Anions

16. A. Elimination Reactions of Dihalides
Treatment of a 1,2 dihaloalkane (vicinal dihalide) with KOH or NaNH2 produces a two-fold elimination of HX and formation of an alkyne
Intermediate is a vinyl halide

17. Vicinal dihalides are available from addition of bromine or chlorine to an alkene

18. Vinyl halides give alkynes when treated with strong base.

19. Dehydrohalogenation of Vicinal dihalides
Dehydrohalogenation of vicinal dihalides results in twofold elimination (loss) of HX and formation of an alkyne
uses strong base (KOH or NaNH2)
Intermediate is a vinyl halide

20. B. Alkylation of Acetylide Anions

21. III. Reactions of Alkynes
Addition of HX and X2
Hydration of Alkynes
Reduction of Alkynes
Oxidative Cleavage of Alkynes

22. III. Reactions of Alkynes
Alkyne Acidity: Formation of Acetylide Anions
Alkylation of Acetylide Anions
An Introduction to Organic Synthesis

23. Introduction
Addition reactions of alkynes are similar to those of alkenes
Alkynes react with many electrophiles to give useful products by addition

24. A. Addition of HX and X2
Addition of excess H-X to an alkyne gives a dihalide product
Regiochemistry is Markovnikov (X attaches to the more highly substituted sp carbon and H adds to the less highly substituted side)

25. Addition of X2 (where X = Br or Cl)
Addition of excess X2 to an alkyne gives a tetrahalide product.
Initial addition of X2 (Br2 or Cl2) to an alkyne gives trans intermediate

26. Addition of HX to Alkynes Involves Vinylic Carbocations

27. 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

28. Vinylic carbocations are less stable than similarly substituted alkyl carbocations.
Vinyl carbocations have sp-hybridized carbons and thus lack stabilizing hyperconjugative interactions
Stability of carbocations:
3º alkyl > 2º alkyl > 1º alkyl ~ 2º vinyl > +CH3 ~ 1º vinyl

29. Addition of HX and X2: Summary
Addition of excess H-X to an alkyne gives a dihalide
Markovnikov Regiochemistry
Addition of excess X2 to an alkyne gives a tetrahalide product.

30. Practice Problem: What products would you expect from the
Practice Problem: What products would you expect from the following reactions?

31. B. Hydration of Alkynes
Hydration of alkynes is the addition H-OH to an alkyne
Mercury (II) catalyzes Markovnikov oriented addition
Hydroboration-oxidation gives the non-Markovnikov product

32. 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 rearranges to a ketone
Alkynes do not react with aqueous protic acids

33. 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

34. Mechanism of Mercury (II) catalyzed Hydration
Addition of Hg(II) to alkyne gives a vinylic carbocation intermediate
Water adds and loses a proton
A proton from aqueous acid replaces Hg(II)

35. Hydration of Unsymmetrical Alkynes
Unsymmetrically substituted internal alkyne:
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

36. Hydration of Unsymmetrical Alkynes
Terminal alkyne
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

37. Mercury(II)-Catalyzed Hydration: Summary
H-OH adds to an alkyne to give an enol which converts to ketone
Markovnikov regiochemistry
Mercury-containing vinylic carbocation intermediate

38. Practice Problem: What product would you obtain by hydration
Practice Problem: What product would you obtain by hydration of the following alkynes?

39. Practice Problem: What alkynes would you start with to prepare
Practice Problem: What alkynes would you start with to prepare the following ketones?

40. 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 Non-Markovnikov orientation
This is opposite to mercuric ion catalyzed hydration

42. Comparison of Hydration of Terminal Alkynes
Hydroboration/oxidation converts terminal alkynes to aldehydes because addition of water is non-Markovnikov
Mercury(II) catalyzed hydration converts terminal alkynes to methyl ketones

43. Hydroboration-oxidation: Summary
Borane adds to an alkyne to give a vinylic borane which is then oxidized by alkaline H2O2 to give an enol which converts to ketone or aldehyde
Non-Markovnikov regiochemistry

44. Practice Problem: What alkyne would you start with to prepare
Practice Problem: What alkyne would you start with to prepare each of the following compounds by a hydroboration/oxidation reaction?

45. C. Reduction of Alkynes
Reduction of alkynes is the addition H-H to an alkyne
Complete Catalytic hydrogenation using a metal catalyst (Pd/C) or
Partial Catalytic hydrogenation using Lindlar catalyst
Reduction with Lithium/ammonia

46. Catalytic Hydrogenation
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 intermediate, which is more reactive than the alkyne so the alkene is not observed

47. Conversion of Alkynes to cis-Alkenes
Addition of H2 using the Lindlar catalyst (chemically deactivated palladium on calcium carbonate) produces a cis alkene
The two hydrogens add syn (from the same side of the triple bond)

48. Conversion of Alkynes to trans-Alkenes
Alkynes are reduced to trans alkenes with sodium or lithium in liquid ammonia
Anhydrous ammonia (NH3) is liquid below -33 ºC
Alkali metals dissolve in liquid ammonia and function as reducing agents
The reaction involves a radical anion intermediate

50. Reduction of Alkynes : Summary
Addition of H2 over a metal catalyst (Pd/C) to an alkyne produces an alkane

51. Addition of H2 using the Lindlar catalyst produces a cis alkene
syn stereochemistry

52. Alkynes are reduced to trans alkenes with sodium or lithium in liquid ammonia
a radical anion intermediate
anti stereochemistry

53. Practice Problem: Using any alkyne needed, how would you
Practice Problem: Using any alkyne needed, how would you prepare the following alkenes?
trans-2-Octene
cis-3-Heptene
3-Methyl-1-pentene

54. D. Oxidative Cleavage of Alkynes
Strong oxidizing reagents (O3 or KMnO4) cleave
internal alkynes, producing two carboxylic acids
terminal alkynes, producing a carboxylic acid and carbon dioxide

55. Neither process is useful in modern synthesis.
Historically, these were used to elucidate structures because the products indicate the structure of the alkyne precursor

56. Oxidative Cleavage of Alkynes: Summary

57. Practice Problem: Propose structures for alkynes that give the
Practice Problem: Propose structures for alkynes that give the following products on oxidative cleavage by KMnO4:

58. E. Alkyne Acidity: Formation of Acetylide Anions
Reaction of strong anhydrous bases (Na+-NH2) with a terminal alkyne produces an acetylide ion
Terminal alkynes are relatively acidic

59. Terminal alkynes are weak Brønsted acids (pKa ~ 25)
Alkenes and alkanes are much less acidic.

60. Acetylide anions are more stable than either alkyl anions or vinylic anions because:
They have sp-hybridized carbon and their negative charge is in a hybrid orbital with 50% s character, allowing the charge to be closer to the nucleus.

61. Formation of Acetylide Anions: Summary
Reaction of strong anhydrous bases (Na+-NH2) with a terminal alkyne produces an acetylide ion

62. Practice Problem: The pKa of acetone, CH3COCH3, is 19. 3
Practice Problem: The pKa of acetone, CH3COCH3, is Which of the following bases is strong enough to deprotonate acetone?
KOH (pKa of H2O =15.7)
Na+ -CΞCH (pKa of C2H2 =25)
NaHCO3 (pKa of H2CO3 = 6.4)
NaOCH3 (pKa of CH3OH = 15.6)

63. F. Alkylation of Acetylide Anions
Reaction of an acetylide anion with a primary alkyl halide produces a larger alkyne
Acetylide anions can react as nucleophiles as well as bases
Acetylide anions can displace a halide ion from a 1o alkyl halide

66. Limitations of Alkylation of Acetylide Ions
Reactions only are efficient with 1º alkyl bromides and alkyl iodides
Acetylide anions can behave as bases as well as nucelophiles
Reactions with 2º and 3º alkyl halides gives dehydrohalogenation, converting alkyl halide to alkene
IE – is the energy required to remove an electron from an atom or ion in the gas phase
Atom in ground state (g) + energy  Atom+ (g) + e- Change in energy = ionization energy
EA – is the energy involved when a gaseous atom absorbs an electron to form a negative ion of the element. Atom (g) + e-  Atom- Change in Energy = EA

67. Alkylation of Acetylide Anions: Summary
Reaction of an acetylide anion with a primary alkyl halide produces a larger alkyne

68. Practice Problem: Show the terminal alkyne and alkyl halide
Practice Problem: Show the terminal alkyne and alkyl halide from which the following products can be obtained. If two routes look feasible, list both:

69. Practice Problem: How would you prepare cis-2-butene starting
Practice Problem: How would you prepare cis-2-butene starting from propyne, an alkyl halide, and any other reagents needed? This problem can’t be worked in a single step. You’ll have to carry out more than one reaction.

70. G. An Introduction to Organic Synthesis
Organic synthesis may be used to
produce new molecules that are needed as drugs or materials
design, test and improve efficiency and safety for making known molecules
test ideas and methods, answering challenges

71. Synthesis as a Tool for Learning Organic Chemistry
In order to propose a synthesis, one 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
IE – is the energy required to remove an electron from an atom or ion in the gas phase
Atom in ground state (g) + energy  Atom+ (g) + e- Change in energy = ionization energy
EA – is the energy involved when a gaseous atom absorbs an electron to form a negative ion of the element. Atom (g) + e-  Atom- Change in Energy = EA

72. 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
IE – is the energy required to remove an electron from an atom or ion in the gas phase
Atom in ground state (g) + energy  Atom+ (g) + e- Change in energy = ionization energy
EA – is the energy involved when a gaseous atom absorbs an electron to form a negative ion of the element. Atom (g) + e-  Atom- Change in Energy = EA

73. Example Problem: prepare octane from 1-pentyne
Strategy: use acetylide coupling
IE – is the energy required to remove an electron from an atom or ion in the gas phase
Atom in ground state (g) + energy  Atom+ (g) + e- Change in energy = ionization energy
EA – is the energy involved when a gaseous atom absorbs an electron to form a negative ion of the element. Atom (g) + e-  Atom- Change in Energy = EA

74. Practice Problem: Beginning with 4-octyne as your only source
Practice Problem: Beginning with 4-octyne as your only source of carbon and using any inorganic reagents necessary, how would you synthesize the following compounds?
Butanoic acid
cis-4-Octene
4-Bromooctane
4-Octanol (4-hydroxyoctane)
4,5-Dichlorooctane

75. Practice Problem: Beginning with acetylene and any alkyl
Practice Problem: Beginning with acetylene and any alkyl halides needed, how would you synthesize the following compounds?
Decane
2,2-Dimethylhexane
Hexanal
2-Heptanone

76. Chapter 8
The End

77. Addition of HX and X2: Summary

78. Hydration of Alkynes
Mercury (II) catalyzes Markovnikov oriented addition
Hydroboration-oxidation gives the non-Markovnikov product

79. Reduction of Alkynes : Summary

80. Oxidative Cleavage of Alkynes: Summary

82. Formation of Acetylide Anions: Summary

83. Alkylation of Acetylide Anions: Summary
Reaction of an acetylide anion with a primary alkyl halide produces a larger alkyne

84. Alkylation of Acetylide Anions: Summary
Reaction of an acetylide anion with a primary alkyl halide produces a larger alkyne