C341/Fall 2011
Chapter 10: Alkynes
Chapter 10: Alkynes
1. Acidity of Alkynes 2. Alkylation of Alkynes 3. Preparation of Alkynes 4. Addition Reactions of Alkynes A. Catalytic Hydrogenation B. Addition of HX (hydrohalogenation) C. Addition of H2O (acid catalyzed hydration) D. Hydroboration‐Oxidation E. Addition of X2 (halogenation) F. Oxidative Cleavage 5. Synthetic Strategies It would be BEST if you did ALL the textbook problems, but at the very least do these: 10.35‐37, 10.40‐44, 10.46, 10.48‐49, 10.51‐53, 10.56‐62, 10.64‐67 Page 1 of 22
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Chapter 10: Alkynes
Alkyne Importance: • More than 1000 different alkyne natural products have been isolated. • One example is histrionicotoxin, which can be isolated from South American frogs, and is used on poison‐tipped arrows by South American tribes. • Ethynylestradiol is the active ingredient in many birth control pills. • The presence of the triple bond increases the potency of the drug compared to the natural analog. Internal alkynes are ca. 4.5 kcal/mol more stable than terminal alkynes. Page 2 of 22
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Chapter 10: Alkynes
1. Acidity of Alkynes Alkynes can be deprotonated with addition of strong enough base. Will NaOCH3 deprotonate an alkyne? What bases will deprotonate an alkyne? A common base used with alkynes is LDA = lithium diisopropylamide: [(CH3)2CH]2N Li Page 3 of 22
C341/Fall 2011
Chapter 10: Alkynes
2. Alkylation of Acetylide Anions Reactions that attach an alkyl group to a molecular frame are called “Alkylation Reactions”. The most common way alkynes are prepared are via alkylation of alkynes. Once the alkyne is deprotonated, it becomes a Nu‐ or base depending on the RX (E+) introduced to it. → Acts like a Nu‐ when reacted with 1o and methyl carbons only → Alkynide ions usually act as bases with 2° or 3° alkyl halides to cause elimination rather than substitution. Page 4 of 22
C341/Fall 2011
Chapter 10: Alkynes
Prepare 2‐pentyne from acetylene (in several steps): Page 5 of 22
C341/Fall 2011
Chapter 10: Alkynes
3. Preparation of Alkynes Alkynes are prepared through an elimination reaction. This reaction occurs with addition of strong bases like:  CH3Li  NaNH2  NaH Two types of dihaloalkanes exist: Page 6 of 22
C341/Fall 2011
Chapter 10: Alkynes
4. A. Addition Reactions of Alkynes – Catalytic Reductions There are three methods to add H2 to a triple bond: i. Catalytic Hydrogenation (Reduction) of Alkynes to Alkanes: H2 gas (moderate pressures = 3 atm; ca. RT) and a catalyst (Pt, Pd or Ni) → it is NOT possible to stop at the alkene product ii. Lindlar catalyst: a special catalyst that reduces an alkyne via syn‐
addition to produce a cis‐alkene only o
Compared to Pd metal above, the Lindlar catalyst is deactivated or considered “poisoned”
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C341/Fall 2011
Chapter 10: Alkynes
iii. Chemical Reduction of an Alkyne ‐ • Alkali metals in NH3(l) leading to anti‐addition and a trans‐alkene product. • Ammonia has a boiling point of –33°C, so the temperature for these reactions must remain very low. • Why can’t water be used as the solvent? Mechanism? Page 8 of 22
C341/Fall 2011
Chapter 10: Alkynes
B. Addition Reactions – hydrohalogenation (HX) What do you notice about the regioselectivity above/below? • Peroxides can be used in the hydrohalogenation of alkynes to promote anti‐Markovnikov addition just like with alkenes. • The process proceeds through a free radical mechanism that we will discuss in detail in Chapter 11 (C342). Page 9 of 22
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Chapter 10: Alkynes
C. Addition Reactions ‐ hydration of alkynes • The process is generally catalyzed with HgSO4 to compensate for the slow reaction rate that results from the formation of vinylic carbocation. • HgSO4 catalyzed hydration involves the mercury (II) ion interacting with the alkyne. O
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Chapter 10: Alkynes
Mechanism of hydration: Page 11 of 22
C341/Fall 2011
Chapter 10: Alkynes
C. Addition Reactions ‐ hydration of alkynes (hydroboration) Overall result is addition of water to a triple bond. o Internal alkynes lead to ketones. o Terminal alkynes add BH2 to the less substituted, terminal carbon. After oxidation to the enol, tautomerization yields an aldehyde, a carbonyl compound having a hydrogen atom bonded to the carbonyl carbon. o In this case, the tautomerization is catalyzed by the base (OH‐) rather than by an acid. o To block out the second unit of BH3 from reacting with the intermediate, bulky borane reagents are often used. Page 12 of 22
C341/Fall 2011
Chapter 10: Alkynes
Predict products for the following reaction. Draw the alkyne reactant and reagents that could be used to synthesize the following molecule. O
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C341/Fall 2011
Chapter 10: Alkynes
D. Addition Reactions – Halogenation • You might expect the mechanism to be similar to the halogenation of alkenes, yet stereochemical evidence suggests otherwise. • The halogenation of an alkene undergoes anti addition ONLY. • The mechanism for alkyne halogenation is not fully elucidated. Page 14 of 22
C341/Fall 2011
E. o
o
o
Chapter 10: Alkynes
Oxidation Reactions of Alkynes – Ozonolysis Alkynes undergo oxidative cleavage of the  and both  bonds. Internal alkynes are oxidized to carboxylic acids (RCO2H). Terminal alkynes afford a carboxylic acid and CO2 from the sp hybridized C—H bond. O3
H2O
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C341/Fall 2011
Chapter 10: Alkynes
5. Synthetic Strategies This entire course will bring you to a point where you can use reactions that you learn to actually pursue organic synthetic problems. Planning a successful synthesis means determining where the target molecule can be broken down into simpler molecules that join together. You will need to be able to: o To plan a synthesis of more than one step, we use the process of retrosynthetic analysis—that is, working backwards from a desired product to determine the starting materials from which it is made. o Break down the carbon skeleton o Look at the functional groups present and determine what reactions you know about those functional groups Page 16 of 22
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Chapter 10: Alkynes
a. f. b. g. c. h. d. i. e. Page 17 of 22
C341/Fall 2011
Chapter 10: Alkynes
Provide reagents for the following scheme: a. b. c. d. e. f. Page 18 of 22
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Chapter 10: Alkynes
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C341/Fall 2011
Chapter 10: Alkynes
Br OH
+ En
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+
HO
Br
+ En
C341/Fall 2011
Chapter 10: Alkynes
The ketone 2‐heptanone has been identified as contributing to the odor of a number of dairy products, including condensed milk and cheddar cheese. Provide a synthesis of 2‐heptanone from acetylene and any necessary reagents. O
HC
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CH
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Chapter 10: Alkynes
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