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. Which compound can most easily undergo elimination to give an alkyne?1. 2. 3. 4. 5. 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 unhybridized pX and py orbitals 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 oC
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 CC bond length is 1.20 Å (C=C is 1.33 Å).
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 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
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. What is the product of the following reaction?1. 2. 3. 4. 5. 1 2 3 4 5

30. If propyne reacts with Br2/H2O following the patterns of electrophilic-addition mechanisms, which of the following is the expected product? 1. 2. 3. 5. 4. 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-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

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

51. The second electron transfer takes place faster than any cis/trans equilibrium of the alkenyl radical.
The final alkene is stable to further reduction by this reagent.

52. Examples:
Sequential one-electron reductions of alkynes produce trans alkenes.
Reduction of alkynes using metallic sodium dissolved in liquid ammonia (dissolving-metal reduction) produces trans alkenes.

53. 2-Hexyne is allowed to react with Li in NH3(liq)
2-Hexyne is allowed to react with Li in NH3(liq). The obtained product is treated with Cl2 in CCl4. Which of the following isomer is main product? 1. 2. 3. 4. 5. 1 2 3 4 5

54. 9.6 Oxidative Cleavage of Alkynes
Strong oxidizing reagents (O3 or KMnO4) cleave internal alkynes, producing two carboxylic acids
Terminal alkynes are oxidized to a carboxylic acid and carbon dioxide
Neither process is useful in modern synthesis – were used to elucidate structures because the products indicate the structure of the alkyne precursor

55. Which compound cannot serve as an immediate precursor to the synthetic target shown below?2. 1. 3. 4. 5. 1 2 3 4 5

56. 9.7 Alkyne Acidity: Formation of Acetylide Anions
Terminal alkynes are weak Brønsted acids (alkenes and alkanes are much less acidic (pKa ~ 25. See Table 8.1 for comparisons))
Reaction of strong anhydrous bases with a terminal acetylene produces an acetylide ion
The sp-hybridization at carbon holds negative charge relatively close to the positive nucleus (Figure 8.5 in text)

57. Terminal alkynes are remarkably acidic.

58. 9.1
Table 8-1, p. 271

59. The electronegativity of a carbon atom depends upon its hybridization
The electronegativity of a carbon atom depends upon its hybridization. The more s character in its hybrid orbitals, the greater the electronegativity.
The acidity of a C-H bond is directly related to the electronegativity of the carbon atom:
Figure 8.5: A comparison of alkyl, vinylic, and acetylide anions. The acetylide anion, with sp hybridization, has more s character and is more stable. Electrostatic potential maps show that placing the negative charge closer to the carbon nucleus makes carbon appear less negative (red).

60. Strong bases such as sodium amide in liquid ammonia, alkyllithiums and Grignard reagents can deprotonate terminal alkynes to the corresponding alkynyl anions.
Alkynyl anions can react as bases and nucleophiles, much like other carbanions.

61. 9.8 Alkylation of Acetylide Anions
Acetylide ions can react as nucleophiles as well as bases (see Figure 8-6 for mechanism)
Reaction with a primary alkyl halide produces a hydrocarbon that contains carbons from both partners, providing a general route to larger alkynes

62. Figure 8.6: MECHANISM: A mechanism for the alkylation reaction of acetylide anion with bromomethane to give propyne.

63. Preparation of Alkynes from Alkynyl Anions
Terminal alkynyl anions will react with alkylating agents such as primary (1o) haloalkanes, oxacyclopropanes, and aldehydes or ketones.
Reaction with secondary and tertiary halides leads to elimination products.

64. Limitations of Alkyation 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

65. Other reactions of alkynyl anions:

66. Which of the following is not a reason for alkyne hydrogens to be more acidic than alkene hydrogens?
the lone pair on alkynyl anion has more s character
the alkynyl anion is more stable
the lone-pair electrons on alkynyl anion are closer to the nucleus
hybridization differences make the vinyl anion less stable
the alkynyl anion is resonance stabilized

67. 9.9 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 efficiency and safety for making known molecules
Highly advanced synthesis is used to test ideas and methods, answering challenges
Chemists who engage in synthesis may see some work as elegant or beautiful when it uses novel ideas or combinations of steps – this is very subjective and not part of an introductory course

68. 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
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

69. 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 (Read the practice problems in the text)
Example
Problem: prepare octane from 1-pentyne
Strategy: use acetylide coupling

70. Naturally Occurring and Physiologically Active Alkynes
Chamomile flower
Chrysanthemum

71. Lower Amazon Indian arrowhead poison.

72. “Poison arrow frog” toxin

73. Naturally occurring antibiotic-antitumor agents.
Nonprescription hypnotic

74. Which of the following molecules cannot be synthesized from propyne using only one reaction?1. 2. 3. 5. 4. 1 2 3 4 5

75. Which reaction sequence would be best to carry out the following transformation?
HBr (1 equivalent) followed by Br2/CCl4
HBr (2 equivalents) followed by Br2/hv
Br2/CH2Cl2 (2 equivalents) followed by H2/Pd/C
Br2/CH2Cl2 (2 equivalents) followed by NaOH
Br2/H2O followed by HBr (2 equivalents)

76. Which reagents are best to carry out the following reaction?
BH3/THF followed by NaOH/H2O2
HgSO4/H2O/H2SO4
NaNH2 followed by CH3I followed by HgSO4/H2O/H2SO4
OsO4 followed by NaHSO3/H2O
KMnO4/H+ followed by CH3I

77. Double bonds can be made by elimination of HX with the help of base, or by elimination of H-OH with the help of acid. Similarly, triple bonds can be made by elimination of two HX molecules with base, but they cannot be made by elimination of two molecules of water with the help of an acid. What is the main reason for this failure?
1,2-Diols cannot be protonated by acids.
In diols, water can be eliminated only with the help of a base.
Formation of a triple bond requires elimination of three molecules of water.
The intermediate carbocation is too unstable.
The intermediate enol tautomerizes to a carbonyl compound.

78. 2-Butyne is allowed to react with H2 over the Lindlar catalysts
2-Butyne is allowed to react with H2 over the Lindlar catalysts. The obtained product is treated with OsO4/pyridine followed by NaHSO3/H2O. Which of the following compounds is the end result of this sequence of reactions? 1. 2. 3. 4. 5. 1 2 3 4 5

79. A reaction of propyne with Hg2+ is run in methanol (CH3OH) in the absence of water, but in the presence of a strong acid (H+) with a non-nucleophilic counterion. If this reaction follows a typical mechanism of electrophilic addition, what would be the expected product? 1. 2. 3. 4. 5. 1 2 3 4 5

80. Consider the carbocations shown below
Consider the carbocations shown below. Which carbocation is more stabilized and why?
The vinyl cation is more stabilized due to resonance.
The vinyl cation is more stabilized because it is a stronger Lewis acid.
The vinyl cation is more stabilized because of hyperconjugation.
The ethyl cation is more stabilized due to a σ*C-H/p orbital interaction.
The ethyl cation is more stabilized due to a σC-H/p orbital interaction.