Presentation on theme: "9. Alkynes: An Introduction to Organic Synthesis"— Presentation transcript:
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 temperatureOur study of alkynes provides an introduction to organic synthesis, the preparation of organic molecules from simpler organic molecules
3 9.1 Naming AlkynesThe 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: IUPACThe 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, RCCH are terminal, those with the structure RCCR’ are internal. Substituents bearing a triple bond are alkynl groups:-CCH is named ethynyl;-CH2CCH is 2-propynyl (propargyl).
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.
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 HXVicinal dihalides are available from addition of bromine or chlorine to an alkeneIntermediate is a vinyl halide
15 Which compound can most easily undergo elimination to give an alkyne? 18.104.22.168.5.12345
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 doubleBreaking 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 -84oCPropyne: b.p oC1-Butyne: b.p. 8.1oC2-Butyne: b.p. 27oCMedium sized alkanes: distillable liquidsAlkynes 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 CC 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 CC 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 alkenesIntermediate alkene reacts further with excess reagentRegiospecificity 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 intermediateSecondary vinyl carbocations form less readily than primary alkyl carbocationsPrimary vinyl carbocations probably do not form at allNonethelss, 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 intermediateProduct with excess reagent is tetrahalideHalogenation takes place once or twice.Halogenation of alkynes proceeds through an isolatable intermediate vicinal dihaloalkene, to the tetrahaloalkane. The two additions are anti.
29 What is the product of the following reaction? 22.214.171.124.5.12345
30 If propyne reacts with Br2/H2O following the patterns of electrophilic-addition mechanisms, which of the following is the expected product?126.96.36.199.4.12345
31 9.4 Hydration of Alkynes Addition of H-OH as in alkenes Mercury (II) catalyzes Markovinikov oriented additionHydroboration-oxidation gives the non-Markovnikov product
32 Mercury(II)-Catalyzed Hydration of Alkynes Alkynes do not react with aqueous protic acidsMercuric ion (as the sulfate) is a Lewis acid catalyst that promotes addition of water in Markovnikov orientationThe 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 cationWater adds and loses a protonA 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 tautomerismEnols rearrange to the isomeric ketone by the rapid transfer of a proton from the hydroxyl to the alkene carbonThe 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 usefulIf 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 alkyneHydration 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 boraneOxidation with H2O2 produces an enol that converts to the ketone or aldehydeProcess 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 ketonesHydroboration/oxidation converts terminal alkynes to aldehydes because addition of water is non-Markovnikov
41 Which is the best starting material to prepare 2-pentanone? pentane1-pentene2-pentene1-pentyne2-pentyne
42 What is the structure of intermediate I? 188.8.131.52.5.12345
43 9.5 Reduction of AlkynesAddition 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 alkeneThe 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 Ap. 268
48 Conversion of Alkynes to trans-Alkenes Anhydrous ammonia (NH3) is a liquid below ºCAlkali metals (Li or Na) dissolve in liquid ammonia and function as reducing agentsAlkynes are reduced to trans alkenes with sodium or lithium in liquid ammoniaThe reaction involves a radical anion intermediate
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?184.108.40.206.5.12345
54 9.6 Oxidative Cleavage of Alkynes Strong oxidizing reagents (O3 or KMnO4) cleave internal alkynes, producing two carboxylic acidsTerminal alkynes are oxidized to a carboxylic acid and carbon dioxideNeither 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? 220.127.116.11.5.12345
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 ionThe sp-hybridization at carbon holds negative charge relatively close to the positive nucleus (Figure 8.5 in text)
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 iodidesAcetylide anions can behave as bases as well as nucelophilesReactions with 2º and 3º alkyl halides gives dehydrohalogenation, converting alkyl halide to alkene
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 characterthe alkynyl anion is more stablethe lone-pair electrons on alkynyl anion are closer to the nucleushybridization differences make the vinyl anion less stablethe alkynyl anion is resonance stabilized
67 9.9 An Introduction to Organic Synthesis Organic synthesis creates molecules by designSynthesis can produce new molecules that are needed as drugs or materialsSyntheses can be designed and tested to improve efficiency and safety for making known moleculesHighly advanced synthesis is used to test ideas and methods, answering challengesChemists 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 reactionsWhat they begin withWhat they lead toHow they are accomplishedWhat the limitations areA synthesis combines a series of proposed steps to go from a defined set of reactants to a specified productQuestions 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 materialConsider 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)ExampleProblem: prepare octane from 1-pentyneStrategy: use acetylide coupling
70 Naturally Occurring and Physiologically Active Alkynes Chamomile flowerChrysanthemum
74 Which of the following molecules cannot be synthesized from propyne using only one reaction? 18.104.22.168.4.12345
75 Which reaction sequence would be best to carry out the following transformation? HBr (1 equivalent) followed by Br2/CCl4HBr (2 equivalents) followed by Br2/hvBr2/CH2Cl2 (2 equivalents) followed by H2/Pd/CBr2/CH2Cl2 (2 equivalents) followed by NaOHBr2/H2O followed by HBr (2 equivalents)
76 Which reagents are best to carry out the following reaction? BH3/THF followed by NaOH/H2O2HgSO4/H2O/H2SO4NaNH2 followed by CH3I followed by HgSO4/H2O/H2SO4OsO4 followed by NaHSO3/H2OKMnO4/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?22.214.171.124.5.12345
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?126.96.36.199.5.12345
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.