1. Chemistry 125: Lecture 53 February 18, 2011 Isoprenoids Tuning Polymer Properties Acetylenes Preliminary This For copyright notice see final page of this file

2. e.g. J&F Sec. 12.13 pp. 554-562 R-L and R + Electrophiles in ** Terpene/Steroid Biogenesis

3. Isopentenyl Pyrophosphate Dimethylallyl Pyrophosphate Adjacent unsaturation apparently speeds S N 2 (as well as S N 1) Cl I benzyl 250 Cl allyl 90 Cl n-propyl k rel for S N 2 with I - in acetone [1] Cl

4. Isopentenyl Pyrophosphate Geranyl Pyrophosphate C5C5 C 10

5. Geranyl Pyrophosphate cis trans Neryl Pyrophosphate Limonene -H +  -Pinene -H + +H 2 O [Ox] Camphor "Terpene" essential oils C 10 Markovnikov anti-Markovnikov

6. Geranyl Pyrophosphate Farnesyl Pyrophosphate "head-to-head reductive dimerization" Squalene (shark liver oil) new bond C 15 “sesquiterpenes” C 30 “triterpenes” e.g. caryophyllene (clove, hemp, rosemary)

7. + Squalene H + + + + + + HO O Markovnikov Anti- Markovnikov Enzyme makes “O” selective among many trisubstituted alkene groups.

8. Squalene + + + + + HO H H H CH 3 H H H + H3CH3C H3CH3C H3CH3C Lanosterol (source of cholesterol & steroid hormones) Not this time! (enzyme control) C 30 “triterpenes” 3°

9. Squalene + + + + + HO H H H CH 3 H H H + H3CH3C H3CH3C H3CH3C Lanosterol (source of cholesterol & steroid hormones) Not this time! (enzyme control) C 30 “triterpenes” 3° Cute Story Is it True? (Wait for NMR)

10. 2 Isoprenes Isoprene H OH Geraniol “dimer” H OH

11. Isoprene OH 2 Isoprenes Menthol “dimer” OH

12. Isoprene O 4 Isoprenes Retinal “tetramer” O

13. Latex “polymer” Isoprene 30,000 Isoprenes

14. Axel Boldt Hevea braziliensis

15. Latex to Caoutchouc

16. Gooey in heat Brittle in cold Thomas Hancock (England -1820) “Masticator” Goodyear (1839) Vulcanization Charles Macintosh (Scotland - 1823) Sandwiched rubber between cloth layers for waterproof garments

17. The occurrence did not at the time seem to them to be worthy of notice; it was considered as one of the frequent appeals that he was in the habit of making, in behalf of some new experiment.” He endeavoured to call the attention of his brother, as well as some other individuals who were present, and who were acquainted with the manufacture of gum-elastic, to this effect, as remarkable, and unlike any before known, since gum-elastic always melted when exposed to a high degree of heat. “He was surprised to find that the specimen, being carelessly brought into contact with a hot stove, charred like leather. Discovery of Vulcanization from Goodyear’s Autobiographical “Gum-Elastic” (1855) 1839

18. Silliman consult “Having seen experiments made, and also performed them myself, with the India rubber prepared by Mr. Charles Goodyear, I can state that it does not melt, but rather chars, by heat, and that it does not stiffen by cold, but retains its flexibility with cold, even when laid between cakes of ice.” B. Silliman October 14, 1839

20. U.S. Pavilion Crystal Palace (1851)

21. Goodyear’s Vulcanite Court India Rubber Desk Mattatuck Museum, Waterbury

22. Somehow Vulcanization joins adjacent chains with sulfur “cross-links” S Latex polymer Radical Addition and Allylic Substitution? H ?

23. Vulcanization and the Physical Properties of Polymers

24. Gough

25. wordsworth “ No floweret blooms Throughout the lofty range of these rough hills, Nor in the woods, that could from him conceal Its birth-place; none whose figure did not live Upon his touch.” Wordsworth “Excursion” (1813) (1757-1825)

26. John Gough Heating rubber makes it expand (more than H 2 O).

28. Heating tightly stretched rubber makes it contract !

29. If stretching rubber generates heat, what should letting it contract do? A) If heat comes from internal friction, contraction should also cause friction and generate heat. B) If heat comes from some other cause, contraction may do the opposite and absorb heat (“generate cold”).

30. Why?

31. View from Yale Health Center

32. Goodyear Inventor

33. Goodyear to Gibbs

34. Gibbs Mathematical Physics J. Willard Gibbs B.A. Yale,1858

35. Gibbs to Onsager

36. Kirkwood & Onsager

37. Polymer Statistical Mechanics

38. Statistics Contracts a Stretched Chain etc. only one arrangement of maximum lengthmany arrangement of shorter length

39. Near maximum extension there is local Crystallization Stretching Rigidity Contributes Rigidity Releases Heat Fixed, irregular cross-links between adjacent chains prevents crystallization (and brittleness) in the cold. Warming “melts” the crystalline regions, and allows statistics to make the material contract. Absorbing heat “melts” the crystalline regions, and allows statistics to make the material contract.

40. Lengthwise Motion by “Reptation” Change shape by snaking along a tunnel through the tangled neighbors. How to make a tangle flow?

41. Sulfur Cross-Links Stop Reptation Vulcanization (no flow when hot) and inhibit crystallization. (not brittle when cold)

42. Vulcanization in the Home

43. Hair before Permanent Wave “Reduce” disulfide cross links with excess basic RSH www.softspikecurlers.com S S S S S S S S RS - - H SR - H RS-SR - H H H H H H (pK a ~11) + NH 4 HS CO 2 HS CO 2 OH or H SR - H Curl with permission

44. Permanent Wave www.softspikecurlers.com H H H H H H BDE kcal/mole HO-OH 52 RS-SR ~ 64 RS-H 87 RO-H 105 S S S S S S S S H H Curl “Oxidize” thiols back to disulfide with HOOH 139169

45. Synthetic Rubber

46. Thermoplastic Ionomers Malleable cross links

47. Julius Nieuwland Cl Neoprene http://lamb.archives.nd.edu/photos/05A-014.htm

48. Natural Rubber vs. Synthetics

49. Radical Polymerization Poly(styrene) Regiochemistry R           R   head-to-tail random ~ 13 kcal/mole more stable than

50. Radical Polymerization Poly(propylene) Tacticity CH 3 H H H H H H H H H H H H H H H H H H H H H H H H H H H Isotactic (Radical) (Ziegler-Natta) Syndiotactic Atactic (Kaminsky)

51. Radical Copolymerization     CO 2 CH 3 Block CO 2 CH 3 Methyl Methacrylate  Styrene CO 2 CH 3 2[1]  0.20.4 k relative      CO 2 CH 3 Alternating ? fastest (good radical)

52. Anti-Hammond Copolymerization     ~ 20 kcal/mole CO 2 CH 3    not as stable but twice as fast!

53. Radical Copolymerization CO 2 CH 3      C=O gives unusually low LUMO. Good when SOMO is not low. “Ionic resonance structure stabilizes transition state.” COCH 3 - O  + - O N.B. This special stability applies in TS only, not in the radical product!

54. 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

55. 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

56. 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 (  ).

57. Hydration and Hydrogenation of Alkynes

58. + 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)

59.  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)

60. 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

61. 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’?)

62. n-Pr-C C-n-Pr Hydrogenation with Either Stereospecificity ( Pd / CaCO 3 / Pb ) H2H2 Lindlar Catalyst C n-Pr H C H 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

63. 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

64. 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

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

66. 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)

67. 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

68. 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

69. 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.

70. C C Conjugation & Aromaticity (Ch. 12-13) Conjugated Pi Systems O C Yoke  Jungere  Jugóm (to Join)

71. 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?

72. When does conjugation make a difference? Experimental Evidence

74. Conjugation worth ~5 kcal Conjugation worth <7 kcal

75. Conjugation worth ~ 4 kcal

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

77. Why is conjugation worth more in allylic systems? Because we can draw reasonable resonance structures? good bad

78. Conjugation & Aromaticity (Ch. 12-13) http://www.chem.ucalgary.ca/SHMO/index.html Simple Hückel MOs

79. : : Sum is same as localized : : Secondary mixing is minor (because of poor E-match) Two Ways to Think about Butadiene  System 4 p-orbitals          How different in overall stability?Very Little! (~3 kcal/mole max) : : Localized  bond picture 4 Delocalized   ::        

80. Two Ways to Think about Butadiene  System 4 p-orbitals                  : : 4 Delocalized   :: Why ignore this mixing? Despite better E-match, it does not lower energy. (What would be gained on one end would be lost on the other) Orthogonal

81. But there are substantial differences in HOMO & LUMO energies (Reactivity), and in HOMO-LUMO gap (color) But there are substantial differences in HOMO & LUMO energies (Reactivity), and in HOMO-LUMO gap (Color). Two Ways to Think about Butadiene  System : : How different in overall stability? Very Little! (~3 kcal/mole max) Localized  bond picture 4 Delocalized   :: far UV (167 nm) nearer UV (210 nm)

82. Is There a Limit to  1 Energy for Long Chains? 8 1/  8 1/8 77/84 1/  4 1/4 33/4 Chain length 2 Normalized AO size 1/  2 Overlap per  bond (AO product) 1/2 Number of  bonds 1 Total overlap stabilization 1/2 N 1/  N 1/N N-1(N-1)/N Yes, the limit is 1, i.e. twice the stabilization of the H 2 C=CH 2  bond. Similarly, the LUMO destabilization limit is twice that of the H 2 C=CH 2   MO.. N.B. Here we are using our own “overlap stabilization” units, which are twice as large as conventional “  ” units.

83. End of Lecture 53 Feb. 19, 2010 Copyright © J. M. McBride 2010. 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

84. End of Lecture 53 February 18, 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