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
H–CC–H + 2H2  CH3CH3 DH = kcal/mol
CH3CH2–CC–H DH = kcal/mol
CH3–CC–CH3 DH = 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 acidity of the hydrogen bonded to a triply bonded carbon
The pKa of acetylene is approximately 25, which makes it a stronger acid than ammonia 7

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 8

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) 9

41. Acidity
Water is a stronger acid than acetylene; hydroxide ion is not a strong enough base to convert acetylene to its anion 10

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. CH3-X CH3CH2-X CH3CH2CH2-X (CH3)2CH-X (CH3)3CCH2-X (CH3)3C-X
جایگزینی نوکلئوفیلی SN2 :
الکیل هالید
نوع
سرعت واکنش
CH3-X
Methyl
CH3CH2-X 1o
100000
CH3CH2CH2-X
40000
(CH3)2CH-X 2o
2500
(CH3)3CCH2-X
1o-neopentyl 1
(CH3)3C-X 3o

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%

51. جایگزینی نوکلئوفیلی SN1 :

52. Alkylation of Acetylide Anions
Reaction with a primary alkyl halide produces a hydrocarbon that contains carbons from both partners, providing a general route to larger alkynes

53. Problem: Which alkyne/alkyl halide combination would work?

54. 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 the efficiency and safety of making known molecules
Highly advanced syntheses are used to test ideas and methods, confirm structures, and demonstrate methods

55. 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

56. Synthesis as a Tool for Learning Organic Chemistry
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 (“roadmap” problem)

57. 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 (retrosynthetic method)
Example
Problem: prepare octane from 1-pentyne
Strategy: use acetylide coupling

58. Synthesis
How in the world
can we be expected
to remember all this?

59. Organic Synthesis A successful synthesis must
provide the desired product in maximum yield
with the maximum control of stereochemistry
and minimum damage to the environment (it must be a “green” synthesis)
Our strategy will be to work backwards from the target molecule 46

60. Organic Synthesis
We use a method called a retrosynthesis and use an open arrow to symbolize a step in a retrosynthesis
Retrosynthesis: a process of reasoning backwards from a target molecule to a set of suitable starting materials
target
molecule
starting
materials 48

61. Practice Problem:

62. Practice Problem:

63. Last step in the synthesis:

64. Making 2-hexyne:

65. Putting it together:

66. Synthesis

67. Synthesis

68. Synthesis

70. gives a mixture

74. Problem: Synthesize from acetylene

75. Problem: Synthesize muscalure (house fly sex attractant)