REAKSI ALKIL HALIDA : SUBSTITUSI DAN ELIMINASI NUKLEOFILIK

1. REAKSI ALKIL HALIDA: SUBSTITUSI DAN ELIMINASI NUKLEOFILIK

2. Nukleofil dan gugus pergi:

3. Reaksi alkil halida dengan nukleofil • Alkil halida terpolarisasi pada ikatan karbon-halida, membuat karbon menjadi elektrofil. • Nukleofil mengganti halida pada ikatan C-X (sebagai basa Lewis) • Nukleofil yang memeiliki basa Brønsted kuat dapat menghasilkan produk eliminasi.

4. Nukleofil • Basa Lewis yang netral atau bermuatan negatif • Perubahan muatan pada reaksi nukleofil • Nukleofil netral menjadi bermuatan positif • Nukleofil bermuatan negatif menjadi netral Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

5. Reaktifitas Relatif Nukleofil • Tergantung pada kondisi reaksi • Nukleofil dengan sifat basa lebih kuat bereaksi lebih cepat untuk struktur yang sama. • Nukleofil yang baik terletak lebih bawah dalam SPU. • Anion biasanya lebih reaktif dari yang netral. Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

6. Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

7. Gugus Pergi • A good leaving group reduces the barrier to a reaction • Stable anions that are weak bases are usually excellent leaving groups and can delocalize charge Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

8. “Super” Leaving Groups Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

9. Poor Leaving Groups • If a group is very basic or very small, it is prevents reaction Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

10. Reaction Kinetics • The study of rates of reactions is called kinetics • The order of a reaction is sum of the exponents of the concentrations in the rate law – the first example is first order, the second one second order.

11. The SN1 and SN2 Reactions • Follow first or second order reaction kinetics • Ingold nomenclature to describe characteristic step: • S=substitution • N (subscript) = nucleophilic • 1 = substrate in characteristic step (unimolecular) • 2 = both nucleophile and substrate in characteristic step (bimolecular)

12. Stereochemical Modes of Substitution • Substitution with inversion: • Substitution with retention: • Substitution with racemization: 50% - 50%

13. SN2 Process • The reaction involves a transition state in which both reactants are together

14. “Walden” Inversion

15. Keadaan Transisi SN2 • Keadaan transisi reaksi SN2 adalah planar, karbon mengikat tiga gugus.

16. Urutan Kereaktifan Reaksi SN2 • Semakin banyak gugus alkil terikat reaksi semakin lambat Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

17. Pengaruh sterik pada Reaksi SN2 The carbon atom in (a) bromomethane is readily accessible resulting in a fast SN2 reaction. The carbon atoms in (b) bromoethane (primary), (c) 2-bromopropane (secondary), and (d) 2-bromo-2-methylpropane (tertiary) are successively more hindered, resulting in successively slower SN2 reactions.

18. Steric Hindrance Raises Transition State Energy Very hindered • Steric effects destabilize transition states • Severe steric effects can also destabilize ground state

19. Sensitive to steric effects Methyl halides are most reactive Primary are next most reactive Secondary might react Tertiary are unreactive by this path No reaction at C=C (vinyl halides) 11.5 Characteristics of the SN2 Reaction

20. The SN1 Reaction • Tertiary alkyl halides react rapidly in protic solvents by a mechanism that involves departure of the leaving group prior to addition of the nucleophile • Called an SN1 reaction – occurs in two distinct steps while SN2 occurs with both events in same step

21. Stereochemistry of SN1 Reaction • The planar intermediate leads to loss of chirality • A free carbocation is achiral • Product is racemic or has some inversion

22. SN1dalam Kenyataannya • Karbokationcenderungbereaksipadasisi yang berlawanandariguguspergilepas • Suggests reaction occurs with carbocation loosely associated with leaving group during nucleophilic addition

23. Effects of Ion Pair Formation • If leaving group remains associated, then product has more inversion than retention • Product is only partially racemic with more inversion than retention • Associated carbocation and leaving group is an ion pair

24. SN1 Energy Diagram Step through highest energy point is rate-limiting (k1 in forward direction) • Rate-determining step is formation of carbocation k1 k-1 k2 V = k[RX]

25. 11.9 Characteristics of the SN1 Reaction • Tertiary alkyl halide is most reactive by this mechanism • Controlled by stability of carbocation

26. Delocalized Carbocations • Delocalization of cationic charge enhances stability • Primary allyl is more stable than primary alkyl • Primary benzyl is more stable than allyl

27. Perbandingan : Mekanisme Substitusi • SN1 • Dua tahap dengan hasil antara karbokation • Terjadi pada 3°, allil, benzil • SN2 • Satu tahap tanpa hasil antara • Terjadi pada alkil halida primer dan sekunder

28. Effect of Leaving Group on SN1 • Critically dependent on leaving group • Reactivity: the larger halides ions are better leaving groups • In acid, OH of an alcohol is protonated and leaving group is H2O, which is still less reactive than halide • p-Toluensulfonate (TosO-) is excellent leaving group Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

29. Allylic and Benzylic Halides • Allylic and benzylic intermediates stabilized by delocalization of charge (See Figure 11-13) • Primary allylic and benzylic are also more reactive in the SN2 mechanism Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

30. Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

31. The Solvent • Solvents that can donate hydrogen bonds (-OH or –NH) slow SN2 reactions by associating with reactants • Energy is required to break interactions between reactant and solvent • Polar aprotic solvents (no NH, OH, SH) form weaker interactions with substrate and permit faster reaction Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

32. Based on McMurry, Organic Chemistry, 6th edition, (c) 2003

33. Polar Solvents Promote Ionization • Polar, protic and unreactive Lewis base solvents facilitate formation of R+ • Solvent polarity is measured as dielectric polarization (P)

34. Solvent Is Critical in SN1 • Stabilizing carbocation also stabilizes associated transition state and controls rate Solvation of a carbocation by water

35. Effects of Solvent on Energies • Polar solvent stabilizes transition state and intermediate more than reactant and product

36. Form dipoles that have well localized negative sides, poorly defined positive sides. Examples: DMSO, HMPA (shown here) Polar aprotic solvents - + + +

37. Common polar aprotic solvents

38. - - - - - - - Cl + + + + + + + + + + + + + + + + + + Polar aprotic solvents solvate cations well, anions poorly + + + + - + + - Na + good fit! bad fit!

39. SN1: Carbocation not very encumbered, but needs to be solvated in rate determining step (slow) Polar protic solvents are good because they solvate both the leaving group and the carbocation in the rate determining step k1! The rate k2 is somewhat reduced if the nucleophile is highly solvated, but this doesn’t matter since k2 is inherently fast and not rate determining.

40. SN2: Things get tight if highly solvated nucleophile tries to form pentacoordiante transition state Polar aprotic solvents favored! There is no carbocation to be solvated.

41. Nucleophiles in SN1 • Since nucleophilic addition occurs after formation of carbocation, reaction rate is not affected normally affected by nature or concentration of nucleophile

42. REAKSI ELIMINASI ALKIL HALIDA • Eliminasi merupakan salah satu jalan alternatif dari suatu reaksi substitusi • Lawan dari reaksi adisi • Menghasilkan alkena • Menurunkan produk substitusi terutama SN1

43. Aturan Zaitsev’s untuk Reaksi Eliminasi (1875) • Pada eliminasi HX dari suatu alkil halida, produk tersubstitusi lebih dominan

44. Mechanisms of Elimination Reactions • Ingold nomenclature: E – “elimination” • E1: X- leaves first to generate a carbocation • a base abstracts a proton from the carbocation • E2: Concerted transfer of a proton to a base and departure of leaving group

45. 11.11 The E2 Reaction Mechanism • A proton is transferred to base as leaving group begins to depart • Transition state combines leaving of X and transfer of H • Product alkene forms stereospecifically

46. Geometry of Elimination – E2 • Antiperiplanar allows orbital overlap and minimizes steric interactions

47. E2 Stereochemistry • Overlap of the developing  orbital in the transition state requires periplanar geometry, anti arrangement Allows orbital overlap

49. Predicting Product • E2 is stereospecific • Meso-1,2-dibromo-1,2-diphenylethane with base gives cis 1,2-diphenyl • RR or SS 1,2-dibromo-1,2-diphenylethane gives trans 1,2-diphenyl (E)-1bromo-1,2-diphenylethene