Alkynes: An Introduction to Organic Synthesis | CHEM 2010, Study notes of Organic Chemistry

Download Alkynes: An Introduction to Organic Synthesis | CHEM 2010 and more Study notes Organic Chemistry in PDF only on Docsity! Alkynes: An Introduction to Organic Synthesis Based on McMurry’s Organic Chemistry, 6th edition, Chapter 8 2 Alkynes  Hydrocarbons that contain carbon-carbon triple bonds  Our study of alkynes provides an introduction to organic synthesis, the preparation of organic molecules from simpler organic molecules 5 8.1 Electronic Structure of Alkynes  Carbon-carbon triple bond results from an sp orbital on each C forming a sigma bond and unhybridized pX and py orbitals forming a π bond  The remaining sp orbitals form bonds to other atoms at 180º (linear geometry) to the C-C triple bond. SS LULU 8.1 Electronic Structure of Alkynes sp orbital .\ a bond ed orbital p orbital sp orbital sp orbitals o bond aw bond Carbon-carbon triple bond @ 2004 Thomson/Brooks Cole 7 8.2 Naming Alkynes  General hydrocarbon rules apply with “yne” as a suffix indicating an alkyne  Numbering of chain with triple bond is set so that the smallest number possible includes the triple bond . Problem 8.1: IUPAC names? CH; CH; CHg (a) onane—crcet, (b) né—eeE, oH, CH, (c) CH,CH=CHCH=CHC =CCH; (d) paenie =CCH,CH,CH, oH, CH, CH; (e) CHG = CEaGH (f) | CH, ©2004 Thomson - Brooks/Cole 10 11 8.3 Preparation of Alkynes: Elimination Reactions of Dihalides  Treatment of a 1,2 dihaloalkane with KOH or NaOH produces a two-fold elimination of HX  Vicinal dihalides are available from addition of bromine or chlorine to an alkene 12 8.3 Preparation of Alkynes: Elimination Reactions of Dihalides  Intermediate is a vinyl halide 15 Addition of Bromine and Chlorine  Initial addition gives trans intermediate  Product with excess reagent is tetrahalide 16 Addition of HX to Alkynes Involves Vinylic Carbocations  Addition of H-X to alkyne should produce a vinylic carbocation intermediate  Secondary vinyl carbocations form less readily than primary alkyl carbocations  Primary vinyl carbocations probably do not form at all SS LULU Vinylic carbocations H ff a “SY i O ames p orbital x oe Vacant p orbital +04 (a Se R @\ 2 on fi sp-hybridized sp*-hybridized A 2° vinylic carbocation a bond A 2° alkyl carbocation 17 20 Keto-enol Tautomerism  Isomeric compounds that can rapidily interconvert by the movement of a proton are called tautomers and the phenomenon is called tautomerism  Enols rearrange to the isomeric ketone by the rapid transfer of a proton from the hydroxyl to the alkene carbon  The keto form is usually so stable compared to the enol that only the keto form can be observed Keto-enol Tautomerism H “~ | 1 Za Co Po Rapid a“ CL a“ H C — °- C | /\ Enol tautomer Keto tautomer (less favored) (more favored) © 2004 Thomson/Brooks Cole 21 22 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.  Hydration of a terminal always gives the methyl ketone 25 8.6 Reduction of Alkynes  Addition 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 26 Incomplete reduction: 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 alkene  The two hydrogens add syn (from the same side of the triple bond) 7-cis-Retinol synthesis (Hoffmann-LaRoche): catalyst S14 7-cis-Retinol (7-cis-vitamin A; vitamin A has a trans double bond at C7) ©2004 Thomson - Brooks/Cole 27 30 8.8 Alkyne Acidity: Formation of Acetylide Anions  Terminal alkynes are weak Brønsted acids (pKa ~ 25).  Reaction of strong anhydrous bases with a terminal acetylene produces an acetylide ion  The sp-hydbridization at carbon holds negative charge relatively close to the positive nucleus, stabilizing the anion. SS Note: pK, of NH, is 33 TABLE 8.1 Acidity of Simple Hydrocarbons Type Example K, pK, Alkyne HC=CH 1Os=2 25 Stronger acid Alkene H,C—CH, 10-44 44 Alkane CH, ~10-© 60 Weaker acid ©2004 Thomson - Brooks/Cole C) mS R—C=C—H + :NHz, Nat — R—C=C:- Nat + :NH; Acetylide anion © 2004 Thomson/Brooks Cole sl H A H f sp? : sp? sp A@ \o H-c=c@® HO / H H Alkyl anion Vinylic anion i . 25% s 33% s —_, — Less stable © 2004 Thomson/Brooks Cole. 35 8.9 Alkylation of Acetylide Anions  Reaction with a primary alkyl halide produces a hydrocarbon that contains carbons from both partners, providing a general route to larger alkynes 36 Limitations of Alkyation of Acetylide Ions  Reactions only are efficient with 1º alkyl bromides and alkyl iodides  Reactions with 2º and 3º alkyl halides gives dehydrohalogenation, converting alkyl halide to alkene SS Prob. 8.11: Which alkyne/alkyl halide combination would work? (a) CHz,CH,CH,C=CCH;, (b) (CH,),CHC=CCH,CH, (c) om 37 40 Synthesis as a Tool for Learning Organic Chemistry  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 (“roadmap” problem) 41 Strategies for Synthesis  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 (retrosynthetic method)  Example Problem: prepare octane from 1-pentyne Strategy: use acetylide coupling SSS LU Practice Prob. 8.1 CH,CH,CH,C=CH ——.. CH,CH,CH,CH,CH,CH,CH,CH, 1-Pentyne Octane © 2004 Thomson/Brooks Cole _ 1. NaNH,, NH; _ CH3;CH,CH,C =CH 2. BrCH,CH,CH,, THF CH;CH,CH,C=CCH.CH,CH; 1-Pentyne 4-Octyne | Here in ethanol H #H CECH —CCH,CH,CH, H H Octane © 2004 Thomson/Brooks Cole 42 . Making 2-hexyne: CH,CH,CH,C=CH + NaNH, “#8. cH,CH,CH,C=C:- Nat 1-Pentyne In THF CH,CH,CH,C=C:- Nat+ CH,| “> CH,CH,CH,C=CCH, 2-Hexyne ©2004 Thomson - Brooks/Cole 45 SS Ul Putting it together: CH,CH,CH, CH; —_— AB N aNHp, NH; —_— Hy — CH,CH,CH,C=CH 9. CHL, THF CH,CH,CH,C=CCH, Lindlar catalyst ps 1-Pentyne 2-Hexyne H H €2004 Thomson - Brooks/Cole Reet 46 — Prob. 8.37: Synthesize from acetylene (a) CH,CH,CH,C=CH (b) CHsCH»C=CCH,CH; i (c) (CH,),CHCH,CH= CH, (d) CH,CH,CH,CCH,CH,CH,CH, (e) CH,CH,CH,CH,CH,CHO ©2004 Thomson - Brooks/Cole 47