Alkynes

Alkynes• Alkynes are molecules that incorporate a CC triple bond

Alkynes• Given the presence of two pi bonds and their associated

electron density, alkynes are similar to alkenes in their ability to act as a nucleophile

• Converting pi bonds to sigma bonds generally makes a molecule more stable.

Alkyne Uses• Acetylene is the simplest alkyne• It is used in blow torches and as a precursor for the

synthesis of more complex alkynes• 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

• An example of a synthetic alkyne is ethynylestradiol

Alkyne Uses

• 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

10.3 Alkyne Acidity• Recall that terminal alkynes have a lower pKa than other

hydrocarbons

• Acetylene is 19 pKa units more acidic than ethylene

Alkyne Acidity• Because acetylene (pKa=25) is still much weaker than

water (pKa=15.7), a strong base is needed to make it react, and water cannot be used as the solvent

• Negative charge is stabilized in sp hybridized orbital

Alkyne Acidity• Use ARIO to rationalize the equilibria below

• A bases conjugate acid pKa must be greater than 25 for it to be able to deprotonate a terminal alkyne

Preparation of Alkynes• Like alkenes, alkynes can also be prepared by

elimination

Preparation of Alkynes• Such eliminations usually occur via an E2 mechanism • Geminal dihalides can be used

• Vicinal dihalides can also be used

• E2 requires anti-periplanar geometry

Preparation of Alkynes: Elimination Reactions of Dihalides

• For geminal dihalides (on C2), can produce either internal or terminal alkyne

Preparation of Alkynes• Often, excess equivalents of NaNH2 are used to shift the

equilibrium toward the elimination products

• NH21- is quite strong, so if a terminal alkyne is produced,

it will be deprotonated• That equilibrium will greatly favor products

Preparation of Alkynes• A proton source is needed to produce the alkyne

• Predict the products in the example below

Reduction of Alkynes• Like alkenes, alkynes can readily undergo hydrogenation• Two equivalents of H2 are

consumed for each alkynealkane conversion

• The cis alkene is produced as an intermediate due to mechanism.

• The addition of the first equivalent of H2 produces an alkene, which is more reactive than the alkyne so the alkene is not observed

Reduction w/ a Poisoned Catalyst• A deactivated or poisoned catalyst can be used to

selectively react with the alkyne

• Lindlar’s catalyst and P-2 (Ni2B complex) are common examples of a poisoned catalysts

Reduction w/ a Poisoned Catalyst• Is this a syn or anti addition?

• 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• The reaction involves a radical anion intermediate

Conversion of Alkynes to trans-Alkenes (Dissolving Metal Reductions)

• Mechanism: Step 1

Dissolving Metal Reductions

• Note the single-barbed and double-barbed (fishhook) arrows.

Dissolving Metal Reductions• Mechanism: Step 1

• The radical anion adopts a trans configuration to reduce repulsion

• Mechanism: step 2 and 3

• Draw the product for step 3 of the mechanism

Dissolving Metal Reductions

• Mechanism: step 4

Dissolving Metal Reductions

• Predict the product(s) for the following reaction

10.5 Dissolving Metal Reductions

• Familiarize yourself with the reagents necessary to manipulate alkynes

• Practice with conceptual checkpoint 10.11

Summary of Reductions

Addition of HX to Alkynes Involves Markovnikov Products

Internal alkynes produce mixture of halogenated alkenes, then Markovnikov product

Terminal alkynes produce Markovnikov product

The associated mechanisms remain to be elucidated

• 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

Hydrohalogenation of Alkynes

• Like alkenes, alkynes can also undergo acid catalyzed Markovnikov hydration

• The process is generally catalyzed with HgSO4 to compensate for the slow reaction rate that results from the formation of vinylic carbocation

• An internal alkyne will generate more than 1 product.

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 with Markovnikov orientation• The immediate product is a vinylic alcohol, or enol, which

spontaneously transforms to a ketone or to an aldehyde in the event that acetylene is employed.

Hydration of Alkynes

• The enol/ketone tautomerization generally cannot be prevented and favors the ketone greatly

• Tautomers are constitutional isomers that rapidly interconvert.

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)

Mechanism of Mercury(II)-Catalyzed Hydration of Alkynes

• Hydroboration-oxidation for alkynes proceeds through the same mechanism as for alkenes giving the anti-Markovnikov product

• It also produces an enol that will quickly tautomerize

• In this case, the tautomerization is catalyzed by the base (OH-) rather than by an acid

Hydroboration-Oxidation

• In general, we can conclude that a C=O double bond is more stable than a C=C double bond.

Hydroboration-Oxidation

• After the –BH2 and –H groups have been added across the C=C double bond, in some cases, an undesired second addition can take place

• To block out the second unit of BH3 from reacting with the intermediate, bulky borane reagents are often used

Hydroboration-Oxidation

B

H

H

RH

B

H

HH

R BH2

Undesired product

H

• Some bulky borane reagents are shown below

Hydroboration-Oxidation

• Predict products for the following reaction

• Draw the alkyne reactant and reagents that could be used to synthesize the following molecule

Hydroboration-Oxidation

O

• Markovnikov hydration leads to a ketone• Anti-Markovnikov hydration leads to an aldehyde

Hydration Regioselectivity

• Initial addition gives trans intermediate as the major product

• Product with excess reagent is tetrahalide• The mechanism for alkyne halogenation is

not fully elucidated

Alkyne Halogenation (Br or Cl)

• Strong oxidizing reagents (O3 or KMnO4) cleave internal alkynes and terminal alkynes; alkyne carbons are fully oxidized

• Neither process is useful in modern synthesis

Oxidative Cleavage of Alkynes

• Predict the product(s) for the following reaction

Alkyne Ozonolysis

O3

H2O

• Terminal alkynes are weak Brønsted acids (alkenes and alkanes are much less acidic (pKa ~ 25. See Table 9.1 for comparisons))

• Reaction of strong anhydrous bases (e.g., sodium amide) with a terminal alkyne produces an acetylide ion

• The sp-hydbridization at carbon holds negative charge relatively close to the positive nucleus (Figure 9.5 in text)

• Acetylide anion is a good nucleophile

Alkyne Acidity: Formation of Acetylide Anions

• Acetylide ions can react as nucleophiles as well as bases• Reaction with a primary alkyl halide produces a hydrocarbon

that contains carbons from both partners, providing a general route to larger alkynes

Alkylation of Acetylide Anions

• 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

Limitations of Alkyation of Acetylide Ions

• Acetylene can be used to perform a double alkylation

• This would involve two separate 2-step reactions• Complex target molecules can be made by building a

carbon skeleton and converting functional groups

Alkylation of Terminal Alkynes

• 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

An Introduction to Organic Synthesis

• 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

Synthesis as a Tool for Learning Organic Chemistry

• 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

Strategies for Synthesis

• Give necessary reaction conditions for the multi-step conversions below

Synthetic Strategies

Br

OH

+

HO

Br+ En + En

Graded HW #1: Synthesis Problems• Give 2 sets of reagents that could be used to synthesize

1-pentyne through elimination reactions.

• Determine necessary reagents to complete the synthesis below.

O