1. Chemistry 125: Lecture 54 February 21, 2011 Acetylenes Allylic Intermediates & Dienes Linear and Cyclic Conjugation (4n+2) Aromaticity This For copyright notice see final page of this file

2. Generalization to Acetylenes e.g. J&F Sec. 10.6-10.11 pp. 444-455 Stepwise / Markovnikov “Keto-Enol Tautomerism” Regioselection Addition of HBr Addition of H 2 O Addition of H 2 Stepwise / Stereoselection Acidity and base-catalyzed isomerization

3. Stepwise Addition of HBr to Alkyne 1-Hexyne + HBr 2-Bromo-1-hexene FeBr 3 15°C with “inhibitor” to trap radicals isolated in 40% yield 100 to 1000x slower than comparable ionic addition to alkene, because vinyl cation is not so great. CH 3 -CH 2 -Cl CH 3 -CH 2 + + Cl - Gas Phase Ionization 193 kcal/mole CH 2 =CH-Cl CH 2 =CH + + Cl - 225 kcal/mole

4. Stepwise Addition of HBr to Alkyne 1-Hexyne + HBr 2-Bromo-1-hexene FeBr 3 15°C with “inhibitor” to trap radicals isolated in 40% yield HBr can add again to the bromoalkene (obviously more slowly) to give a second Markovnikov addition If the bromo substituent slows addition to an alkene, why is there Markovnikov orientation? 2,2-Dibromohexane Br is a “schizophrenic” substituent: both electron withdrawing (  ), and electron-donating (  ).

5. Hydration and Hydrogenation of Alkynes

6. + Hg(OAc) 2 H + / H 2 O HC CR + HC CR HgOAc C O R C H H2OH2O -H + H+H+ NaBH 4 C O R C H H H H Markovnikov Enol H + H Ketone an easy allylic rearrangement “Keto-Enol Tautomerism” + (favors ketone Cf. Lecture 37)

7.  ve Bond Energies Can one sum bond energies to get accurate"Heats of Atomization"? H C O H C C H H H H H C O H C C H H H H Ketone "Enol" C O C H C O C H C=O179 C-C83 C-H99 sum361 C-O86 C=C146 O-H111 sum343 K calc = 10 -(3/4) 18 = 10 -13.5 K obs = 10 -7 = 10 -(3/4) 9.3 Bonds that change (the others should cancel in taking the difference)

8. H C O H C C H H H H H C O H C C H H H H Ketone "Enol" H Why is Enol 9 kcal/mole "Too" Stable? O C=O179 C-C83 C-H99 sum361 C-O86 C=C146 O-H111 sum343 K calc = 10 -(3/4) 18 = 10 -13.5 K obs = 10 -7 = 10 -(3/4) 9.3 C(sp 2 )-H stronger than C(sp 3 )-H (they shouldn’t actually cancel) Intramolecular HOMO-LUMO Mixing H C O H C C H H H H + "Resonance Stabilization” from

9. Markovnikov Enol + Hg(OAc) 2 H + / H 2 O HC CR + HC CR HgOAc C O R C H H2OH2O -H + H + H Ketone R’ 2 B-H HC CR C R R’ 2 B C H H Anti-Markovnikov Enol Aldehyde HOOH HO - C R HO C H H H vinylborane (hindered R’ 2 BH adds only once) BH 3 + 2 e.g. “disiamylborane” Hydration with Either Regiospecificity (what is R’?)

10. R-C C-R Hydrogenation with Either Stereospecificity ( Pd / CaCO 3 / Pb ) H2H2 Lindlar Catalyst C R H C H R deactivate Pd to stop at alkene n-Pr-C C-n-Pr Na / NH 3 C n-Pr H C H “dissolving metal reduction” syn addition H H anti addition H H 97% for R = (CH 2 ) 3 CO 2 CH 3 80-90%

11. solvated electron Na NH 3 e - (NH 3 ) n + Na + R-CC-R First H + R-CC-R R-CC-R e-e- First e - CC R R H C C RR H Vinyl radicals are sp 2 but they invert easily H NH 2

12. Second H + e-e- H NH 2 C C R R H Vinyl anions are sp 2 and invert very slowly (remember XH 3 ) Second e - CC R R H CC RR H Vinyl radicals are sp 2 but they invert easily C C R R H H anti addition (because of radical isomerism) H H

13. Alkyne Acidity and Isomerization e.g. J&F Sec. 12.4 pp. 516-518

14. Approximate “pK a ” Values CH 3 -CH 2 CH=CHH ~ 44 CH 3 -CH 2 C CH ~ 25 CH 3 -CH=C=CHH CH 3 -C C-CH 2 H ~ 38 sp 3 C _ sp 2 C _ (no  overlap) sp C _ (no  overlap) C _ HOMO -  overlap CH 3 -CH 2 CH 2 CH 2 H ~ 52 ~ 34 H 2 NH = 16 HOH (better E-match N-H ) (bad E-match O-H ) (best E-match C-H ) 50 40 30 20 10 pK a * : : (allylic) (e.g. J&F Acidity of 1-Alkynes Secs. 3.14 p. 129; 12.4 p. 516-518)

15. H + (aq) + Equilibrium & Rate kcal/mol 40 30 20 10 -10 50 0 CH 3 -CH=C=CH 2 CH 3 -C C-CH 3 CH 3 -CH 2 C CH CH 3 -CH 2 C C CH 3 -CH=C=CH CH 3 -C C-CH 2 pK a  38 K a  10 -38  G  4/3  38 = 51 pK a  25 K a  10 -25  G  4/3  25 = 33 4.1 4.8 0.1%0.03% k  10 13  10 -38 /sec t 1/2 = 0.69/k  10 25 sec = 10 17 yrs  10 4  time since Big Bang [0] at equilibrium

16. H + (aq) + + HO - favors dissn. by 21 kcal (4/3  16) Equilibrium & Rate kcal/mol 40 30 20 10 -10 50 0 CH 3 -CH=C=CH 2 CH 3 -C C-CH 3 CH 3 -CH 2 C CH CH 3 -CH 2 C C CH 3 -CH=C=CH CH 3 -C C-CH 2 t 1/2  30 yrs @ 300K -7.2 0.0001%  2 min @ 150°C + H 2 N - favors dissn. by 45 kcal (4/3  34) at equilibrium

17. Trick to obtain terminal acetylene: Equilibrate with RNH _ base (in RNH 2 solvent at room temp) to form terminal anion. “Quench” by adding water which donates H + to terminal anion and to RNH _, leaving OH _, which is too weak to allow equilibration. Or add H +, so even [OH _ ] is very low.

18. C C Conjugation & Aromaticity Conjugated Pi Systems O C Yoke  Jungere  Jugóm (to Join) e.g. J&F Ch. 12-13

19. The Localized Orbital Picture (Pairwise MOs and Isolated AOs) Is Our Intermediate between H-like AOs and Computer MOs When must we think more deeply?

20. When does conjugation make a difference? Experimental Evidence

21. Allylic Stabilization: Cation R-Cl  R + + Cl - (gas phase kcal/mol) Cl 193 172 171 Anion pK a OH 16 10 5OH O Radical Bond Dissociation Energy (kcal/mol) H H 101 89 Conjugation worth ~ 13 kcal ! as good as secondary 4/3  6 = 8 kcal

22. Br - -78°C 20% 80% 85% 15% Allylic Cation Intermediates: Addition of HX to Butadiene HBr -78°C e.g. J&F Sec. 12.9-12.10 pp. 534-541 H + + H + H H Br H Kinetic vs. Thermodynamic Control Reason for Kinetic Distribution? FeBr 3

23. +17.6 -21.4 HOMO-4HOMOLUMO+1 LUMO HOMO-1LUMO+1LUMOHOMO Butadiene Propenyl Cation H+H+ hyperconjugated  C-H best overlap best potential best product best overlap

24. Propenyl Cation +152 +144 +132 +99 Surface Potential best potential best  potential

25. symmetrical (but for D) p. 1288 3.1 : 1 -78° 1.6 : 1 25° Cl - D Cl rapid ion-pair collapse competes with motion

26. Allylic Transition States: S N 1 e.g. J&F Sec. 12.11a,b pp. 541-543 k rel for solvolysis in 1:1 EtOH/H 2 O at 45°C Cl << 0.01 Cl 0.01 Cl 6300 Cl 43 Cl 0.05 Cl 0.07 Cl [100] Cl 39 ++ methylation is effective where charge is (C1,C3)

27. Allylic Transition States: S N 2 e.g. J&F Sec. 12.11a,b pp. 541-543 k rel for Displacement by EtO - in EtOH at 45°C Cl [1] Cl 560 Cl 97 Cl 37 Cl 33 Cl 1.9

28. Allylic Anion Intermediates: RH Acidity allylic benzylic e.g. J&F Sec. 12.11d pp. 543-544 and Sec. 13.12 pK a ~52 H CH 2 pK a 43 H CH 2 pK a 41 H CH 2 4/3 x 9 ≈ 11 kcal/mole 4/3 x 12 ≈ 16 kcal/mole

29. Allylic Free-Radical Intermediates: Allylic Bromination Cf. J&F Sec. 11.8 pp. 497-500, Sec. 12.11c p. 543 N-Bromosuccinimide (NBS) N O O Br 58% yield K. Ziegler (1942) Et 2 O 30 min. h

30. Ionic Preparation and Destruction of NBS pK a 9.5 N O O H NaOH 0°C N-N- O O N O O Br Br 2 + NaBr N OH O Br + N OH O undo with HBr N OH O Br + Br - “enol” to “ketone” Br - + Br 2

31. Br How to control Addn. vs. Subst.? Rate  [Br 2 ] 2 Br 2 helps Br - leave from “Br +” in nonpolar solvent (like protonation of OH) Whenever a Br 2 molecule is consumed, one new Br 2 molecule is created. Allylic Reactivity - Radical Automatically maintains minimal [Br 2 ]. + Br 2 + Br-Br-Br - Br + CH 2 Cl 2 25°C Dark H H or H Br H Br 2 + Br N O O BrN O O H Addition Substitution 2 H Br initiator (h, peroxide, etc.) Keep dark + HBr slow (selective) or minimize [Br 2 ] (tedious to impossible?) Cl also attacks this CH 2 group

32. Conjugation worth ~7 kcal Conjugation worth ~8 kcal  H combustion 768.9 ±0.3 761.6 ±0.2 17.7 25.4  H formation Diene Stabilization:

33. Conjugation worth ~ 4 kcal/mole  H hydrogenation (kcal/mole) -30.2 -29.8 -30.0 -56.5 -60.4 -60.0

34. End of Lecture 54 February 21, 2011 Copyright © J. M. McBride 2011. Some rights reserved. Except for cited third-party materials, and those used by visiting speakers, all content is licensed under a Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0).Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0) Use of this content constitutes your acceptance of the noted license and the terms and conditions of use. Materials from Wikimedia Commons are denoted by the symbol. Third party materials may be subject to additional intellectual property notices, information, or restrictions. The following attribution may be used when reusing material that is not identified as third-party content: J. M. McBride, Chem 125. License: Creative Commons BY-NC-SA 3.0