Chapter 7 Outline: It takes...

C341/Spring 2010 Chapter 7

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Chapter 7 Outline: It takes Alkynes!!

1. Structure of Alkynes (practice nomenclature on your own)

2. Preparation of Alkynes

3. Reactions of Alkynes

A. Acidity of Alkynes

B. Alkylation of Acetylide Anions

C. Electrophilic Additions

i. Halogenation of Alkynes

ii. Hydration of Alkynes

iii. Hydroboration

D. Reductions of Alkynes

E. Oxidations of Alkynes

4. Organic Synthesis

Chapter 7 parallels chapter 6 (alkenes) in many ways, but there are some twists. However, this will be a good review for what you learned already. Suggested homework problems: 7.7, 7.8, 7.10-7.12, 7.14, 7.16,- 7.18, 7.20-7.25, 7.27, 7.29-7.32.


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Road Map of Alkyne Reactions (11 reactions)

2 NaNH2

H

O

H

O

Br Br

XX

X X

2 X2

H2SO4,HgSO4, H2O

1. Strong base2. CH3X

2 HX1. BH3(THF)2. NaOH, H2O2

H2, Pd, high P

Lindlar PdH2

Na, NH31. O32. H2O

O

OH

O

OH+

1. O32. H2O

O

OH+ CO2


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1. Structure of Alkynes

o Internal alkynes are ca. 4.5 kcal/mol more stable than terminal alkynes. o Triple bond must be written linearly.

o General molecular formula CnH2n-2

o The triple bond introduces two degrees of unsaturation and contains two

nucleophiles.


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2. Preparation of Alkynes by Elimination Alkynes are prepared through an elimination reaction (opposite of addition reaction). This mechanism will be covered in depth in chapter 9. This reaction occurs with addiation of strong bases like:

• CH3Li • NaNH2 • NaH

Two types of dihaloalkanes exist:


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3. Reactions of Alkynes A. Deprotonation 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


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B. 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

1. NaNH22. CH3CH2I

H → Acts like a base when reacted with 2o and 3o RX

1. NaNH22.

H

Br


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Prepare 2-pentyne from acetylene (in several steps):


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C. Electrophilic Addition to Alkynes You know both of these mechanisms from chapter 6, so you can practice doing them twice in a row.

i. Hydrohalgenation of Alkynes

Markovkinov’s rule still applies! (Nu adds to the most substituted carbon)

ii. Halogenation of Alkynes

Halogens, X2 (X = Cl or Br), add to alkynes just as they do to alkenes.


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iii. Hydration – Electrophilic addition water to alkynes

o Internal alkynes undergo hydration solely with concentrated acid.

o Terminal alkynes require the presence of an additional Hg2+ catalyst (to make it

easier, we will add Hg2+ salts with all alkynes).

This reaction goes through tautomerization spontaneously once the enol is formed. Keto-enol tautomerism occurs quickly:

Tautomers are constitutional isomers that differ in the location of the double bond and a hydrogen atom. These tautomers exist in equilibrium together. Equilibrium favors the keto form due the higher bond strength of C=O > C=C.

Ka = 106

Tautomerization is the process that converts one tautomer to the other. This process is catalyzed by either acid or base.


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Mechanism of hydration:


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Tautomers: Practice writing the following ketones as enols and assessing stability:


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iii. Hydroboration (yes, AGAIN!) Hydroboration takes an alkyne to an alkene (similar to chapter 6 taking an alkene to an alkane).

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.


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Overview of alkynes with boranes:

a.

b.

c.


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D. Reduction of Alkynes (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 “Lindlar Pd: is:

o finely powdered Pd deposited on CaCO3, lead salts and a base like quinoline.

Quinoline:

o Compared to Pd metal above, the Lindlar catalyst is deactivated or “poisoned”

iii. Chemical Reduction of an Alkyne - Alkynes may be reduced in the presence of

alkali metals in NH3(l) leading to anti-addition and a trans-alkene product.


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E. Oxidative Cleavage of Alkynes

o Alkynes undergo oxidative cleavage of the σ and both π bonds. o Internal alkynes are oxidized to carboxylic acids (RCO2H).

o Terminal alkynes afford a carboxylic acid and CO2 from the sp hybridized

C—H bond.


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Practice Addition Reactions of Alkynes

a.

Br Br2 NaH

b.

c.

d.

e.


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Problem 7-20: Provide correct reagents for the following scheme.

a.

b.

c.

d.

e.

f.

g.

h.

i.


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Problem 7-21: Provide reagents for the following scheme.

a.

b.

c.

d.

e.

f.


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Retrosynthesis – putting several reactions together This entire course will bring you to a point where you can use reactions that you learn to actually pursue organic synthesic 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 Use open arrows to denote retrosynthetic steps:


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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.


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Provide a synthesis that could bring about this reaction.

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