Organic Chemistry Second Edition Chapter 10 David Klein Alkynes Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.1 Alkynes Alkynes are molecules that incorporate a CC triple bond Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.1 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. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.1 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 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.1 Alkyne Uses An example of a synthetic alkyne is ethynylestradiol How do you think a CC triple bond affects the molecules geometry? Its rigidity? Its intermolecular attractions? 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 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.2 Alkyne Nomenclature Alkynes are named using the same procedure we used in Chapter 4 to name alkanes with minor modifications Identify the parent chain, which should include the CC triple bond Identify and Name the substituents Assign a locant (and prefix if necessary) to each substituent giving the CC triple bond the lowest number possible List the numbered substituents before the parent name in alphabetical order. Ignore prefixes (except iso) when ordering alphabetically The CC triple bond locant is placed either just before the parent name or just before the -yne suffix Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.2 Alkyne Nomenclature Alkynes are named using the same procedure we used in Chapter 4 to name alkanes with minor modifications Identify the parent chain, which should include the CC triple bond Identify and name the substituents. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.2 Alkyne Nomenclature Alkynes are named using the same procedure we used in Chapter 4 to name alkanes with minor modifications Assign a locant (and prefix if necessary) to each substituent giving the CC triple bond the lowest number possible The locant is ONE number, NOT two. Although the triple bond bridges carbons 2 and 3, the locant is the lower of those two numbers Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.2 Alkyne Nomenclature Alkynes are named using the same procedure we used in Chapter 4 to name alkanes with minor modifications List the numbered substituents before the parent name in alphabetical order. Ignore prefixes (except iso) when ordering alphabetically The CC triple bond locant is placed either just before the parent name or just before the -yne suffix Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.2 Alkyne Nomenclature In addition to the IUPAC naming system, chemists often use common names that are derived from the common parent name acetylene You should also be aware of the terminology below Practice with SkillBuilder 10.1 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.2 Alkyne Nomenclature Name the molecule below Recall that when triple bonds are drawn their angles are 180° Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.3 Alkyne Acidity Recall that terminal alkynes have a lower pKa than other hydrocarbons Acetylene is 19 pKa units more acidic than ethylene, which is 1019 times stronger Does that mean that terminal alkynes are strong acids? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.3 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 Recall from chapter 3 we used the acronym, ARIO, to rationalize differences in acidity strengths Use ARIO to explain why acetylene is a stronger acid than ethylene which is stronger than ethane Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.3 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 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.4 Preparation of Alkynes Like alkenes, alkynes can also be prepared by elimination Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.4 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 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.4 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 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.4 Preparation of Alkynes A proton source is needed to produce the alkyne Predict the products in the example below Practice with conceptual checkpoint 10.7 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.5 Reduction of Alkynes Like alkenes, alkynes can readily undergo hydrogenation Two equivalents of H2 are consumed for each alkynealkane conversion The cis alkene is produced as an intermediate. WHY cis? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.5 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 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.5 Reduction w/ a Poisoned Catalyst Is this a syn or anti addition? Practice with conceptual checkpoint 10.9 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.5 Dissolving Metal Reductions Reduction with H2 gives syn addition Dissolving metal conditions can give Anti addition producing the trans alkene Ammonia has a boiling point = -33°C, so the temperature for these reactions must remain very low Why can’t water be used as the solvent? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.5 Dissolving Metal Reductions Mechanism: Step 1 Note the single-barbed and double-barbed (fishhook) arrows. Why does Na metal so readily give up an electron? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.5 Dissolving Metal Reductions Mechanism: Step 1 Why is the first intermediate called a radical anion? The radical anion adopts a trans configuration to reduce repulsion Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.5 Dissolving Metal Reductions Mechanism: step 2 and 3 Draw the product for step 3 of the mechanism Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.5 Dissolving Metal Reductions Mechanism: step 4 Do the pKa values for NH3 and the alkene favor the proton transfer? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.5 Dissolving Metal Reductions Predict the product(s) for the following reaction Practice with conceptual checkpoint 10.10 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.5 Summary of Reductions Familiarize yourself with the reagents necessary to manipulate alkynes Practice with conceptual checkpoint 10.11 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.6 Hydrohalogenation of Alkynes Like alkenes, alkynes also undergo hydrohalogenation Draw the final product for the reaction above Do the reactions above exhibit Markovnikov regioselectivity? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.6 Hydrohalogenation of Alkynes You might expect alkynes to undergo hydrohalogenation by a mechanism similar to alkenes Yet, the mechanism above does not explain all observed phenomena A slow reaction rate, 3rd order overall rate law, like 1° carbocations, vinylic carbocations are especially unstable Vinylic carbocation Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.6 Hydrohalogenation of Alkynes Kinetic studies on the hydrohalogenation of an alkyne suggest that the rate law is 1st order with respect to the alkyne and 2nd order with respect to HX What type of collision would result in such a rate law? Unimolecular, bimolecular, or termolecular? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.6 Hydrohalogenation of Alkynes Reaction rate is generally slow for termolecular collisions. WHY? Considering the polarizability of the alkyne, does the mechanism explain the regioselectivity? May involve multiple competing mechanisms Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.6 Hydrohalogenation of Alkynes Peroxides can be used in the hydrohalogenation of alkynes to promote anti-Markovnikov addition just like with alkenes Which product is E and which is Z? The process proceeds through a free radical mechanism that we will discuss in detail in Chapter 11 Practice with conceptual checkpoint 10.13 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.7 Hydration 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 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.7 Hydration of Alkynes HgSO4 catalyzed hydration involves the mecury (II) ion interacting with the alkyne Can you imagine what that interaction might look like and how it will increase the rate of reaction for the process? Why is the intermediate called an enol? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.7 Hydration of Alkynes The enol/ketone tautomerization generally cannot be prevented and favors the ketone greatly Tautomers are constitutional isomers that rapidly interconvert. How is that different from resonance? Practice with SkillBuilder 10.3 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.7 Hydroboration-Oxidation 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 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.7 Hydroboration-Oxidation In general, we can conclude that a C=O double bond is more stable than a C=C double bond. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.7 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 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.7 Hydroboration-Oxidation Some bulky borane reagents are shown below Practice with conceptual checkpoint 10.20 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.7 Hydroboration-Oxidation Predict products for the following reaction Draw the alkyne reactant and reagents that could be used to synthesize the following molecule Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.7 Hydration Regioselectivity Markovnikov hydration leads to a ketone Anti-Markovnikov hydration leads to an aldehyde Practice with SkillBuilder 10.4 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.8 Alkyne Halogenation Alkynes can also undergo halogenation Two equivalents of halogen can be added You might expect the mechanism to be similar to the halogenation of alkenes, yet stereochemical evidence suggests otherwise – see next slide Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.8 Alkyne Halogenation When one equivalent of halogen is added to an alkyne, both anti and syn addition is observed The halogenation of an alkene undergoes anti addition ONLY The mechanism for alkyne halogenation is not fully elucidated Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.9 Alkyne Ozonolysis When alkynes react under ozonolysis conditions, the pi system is completely broken The molecule is cleaved, and the alkyne carbons are fully oxidized Practice with conceptual checkpoint 10.25 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.9 Alkyne Ozonolysis Predict the product(s) for the following reaction Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.10 Alkylation of Terminal Alkynes As acids, terminal alkynes are quite weak Yet, with a strong enough base, a terminal alkyne can be deprotonated and converted into a good nucleophile What has a higher pKa, NH3 or R-CC-H? WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.10 Alkylation of Terminal Alkynes The alkynide ion can attack a methyl or 1° alkyl halide electrophile Such reactions can be used to develop molecular complexity Alkynide ions usually act as bases with 2° or 3° alkyl halides to cause elimination rather than substitution Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.10 Alkylation of Terminal Alkynes Acetylene can be used to perform a double alkylation Why will the reaction be unsuccessful if the NaNH2 and Et-Br are added together? Complex target molecules can be made by building a carbon skeleton and converting functional groups Practice with SkillBuilder 10.5 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.11 Synthetic Stategies Recall the methods for increasing the saturation of alkenes and alkynes But, what if you want to reverse the process or decrease saturation? See next slide Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.11 Synthetic Stategies Halogenation of an alkene followed by two dehydrohalogenation reactions can decrease saturation We will have to wait until chapter 11 to see how to convert an alkane into an alkene, but here is a preview What conditions would you use in step B? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.11 Synthetic Stategies In the alkene to alkyne conversion above, why is water needed in part 3) of that reaction? Practice with SkillBuilder 10.6 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

10.11 Synthetic Stategies Give necessary reaction conditions for the multi-step conversions below Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Additional Practice Problems Name the molecule Draw the structure of 2,2-dimethyl-6-chloro-3-heptyne Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Additional Practice Problems Give 2 sets of reagents that could be used to synthesize 1-pentyne through elimination reactions. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Additional Practice Problems Give a set of reagents that could be used to synthesize cis-2-pentene from an addition reaction. Give a set of reagents that could be used to synthesize trans-2-pentene from an addition reaction. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Additional Practice Problems Give a set of reagents that could be used to synthesize a ketone from an addition reaction. Give a set of reagents that could be used to synthesize an aldehyde from an addition reaction. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Additional Practice Problems Determine necessary reagents to complete the synthesis below. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e