Materi Kuliah - Organic Chemistry Lecture.pptx

Organic Chemistry

1. Chapter 8-9 Lecture PowerPoint Nucleophilic Substitution and Elimination Reactions

2. S N 1: Substitution, Nucleophilic, Unimolecular A nucleophilic substitution reaction taking place in two steps is an example of a unimolecular nucleophilic substitution (S N 1) mechanism.

3. Four-way Rate Competition S N 2 S N 1 E1 E2

4. S N 1: Substitution, Nucleophilic, Bimolecular S N 1 reaction mechanism takes place in a two steps The C–L bond breaks first to give a carbocation intermediate This intermediate can then react with a nucleophile

5. S N 1 free energy diagram - maps D E as reaction progresses S N 1: Substitution, Nucleophilic, Bimolecular Two ‡s Highest E A gives the rate limiting step Carbocation intermediate

6. Factor 1: Structure of R-X/LG Empirical data for S N 1 reactions:

7. Factor 1: Structure of R-X/LG When S N 1 (top) compared with S N 2 rates (bottom), we see that the two reactions are opposite in their requirements for the structure of R-X For S N 1: 3 o > 2 o >> 1 o /CH 3 (never)

8. Hammond Postulate

9. The Hammond Postulate Applied to S N 1 In SN1 the rate limiting step is the formation of the intermediate C + This step is endothermic By the Hammond postulate ‡ 1 resembles the intermediate in energy The ‡ for a more stable carbocation is lower, so E A is reduced Therefore a more stable carbocation will increase the rate of S N 1

10. Carbocation Stability Carbocations formed in S N 1 processes are sp 2 hybridized, trigonal planar species with an empty p-orbital This species is highly e - deficient carbon and very reactive When we discuss a ‘stable’ carbocation, it is relative to other carbocations -–all of them are highly reactive!

11. Carbocation Stability Observed carbocation stabilities: Electrostatic potential plots show large difference in positive charge character:

12. Carbocation Stability Carbocation stability is the result of hyperconjugation . Hyperconjugation is the spreading out of charge by the overlap of an empty p orbital with an adjacent  bond. This overlap delocalizes the positive charge on the carbocation over a larger volume, thus stabilizing it. Here, (CH 3 ) 2 CH + can be stabilized by hyperconjugation , but CH 3 + cannot:

13. Carbocation Stability Hyperconjugation is a similar effect to the structure of a p -bond. A p -bond is the parallel overlap of two orbitals to make a stable bond The overlap of a 2-e - s -bond with the empty p -orbital is not as efficient, but stabilizes the empty orbital Note the back lobe of the sp 3 orbital is also in position to overlap and stabilize the empty p -orbital

14. Benzyl and allyl carbocations are stabilized by direct conjugation and resonance contributors A 1 o allyl cation is about as stable as a 2 o carbocation A 1 o benzyl cation is about as stable as a 3 o carbocation Carbocation Stability

15. S N 1 Rate Determining Step The S N 1 reaction takes place in two steps. The first step is rate determining because formation of the carbocation is much slower than formation of the final product.

16. Rate of an S N 1 Reaction Consider the observed kinetics for the following S N 1 reaction: NaSH HS

17. Rate of an S N 1 Reaction Note that in the free energy diagram, only the C-LG species is involved in the rate limiting step The empirical evidence led to the S N 1 mechanism, where only the bond breaking between C-LG is involved in the rate. The nucleophile is not involved in the rate law! ANY nucleophile will work, even weak ones!

18. Rate of an S N 1 Reaction

19. Due to the observation that the nucleophile does not participate in the rate limiting step, the Nu: has no effect on the S N 1 process However, as we will see in Factor 4, the solvent of an S N 1 reaction will often also act as the nucleophile These are referred to as solvolysis reactions Factor 2: Strength of the Nu:

20. Factor 3: Leaving Group Ability A leaving group must leave in the rate-determining step of an S N 2, S N 1, E2, or E1 reaction. The identity of the leaving group has an effect on the rate of each reaction. A good leaving group is necessary for the reaction to be exothermic (and spontaneous) via a – D H Leaving group ability strongly affects S N 1 reactions

21. Factor 3: Leaving Group Ability Experimental Data: Good LGs Never LGs

22. Factor 3: Leaving Group Ability Overall, S N 1 is similar to S N 2 as far as leaving group ability: Are never LGs!

23. Factor 4: Solvent Effects Empirical data: Rate of S N 1 reactions in various solvents: H 2 O

24. Factor 4: Solvent Effects Observation: S N 1 reactions are most rapid in polar protic solvents Consider the dissolution of NaCl in H 2 O. The ionic bond in NaCl is 410 kJ/mole in strength. Water is has a strong dielectric and orients to insulate opposing charges from one another: This allows the Na ion to be separated from the Cl ion at room temperature

25. Factor 4: Solvent Effects In an S N 1 reaction the polar protic solvent has the same effect This stabilizes both cation and anion and facilitates the rate limiting step of the S N 1 reaction:

26. Factor 4: Solvent Effects There is a limitation with this. Unlike the NaCl example, where no further reaction between H 2 O and Na + or Cl - can occur, the carbocation is highly reactive. With the lone pair of oxygen in proximity to stabilize, it often becomes the nucleophile!

27. Factor 4: Solvent Effects This is called solvolysis , where the solvent becomes the nucleophile in S N 1 and substitutes for the leaving group. This reaction requires a third mechanistic step to deprotonate the O

28. Factor 4: Solvent Effects If solvolysis is desired, the reaction is simply run in that solvent If solvolysis is not desired, if another nucleophile is present, it will tend to react ultimately as -OH 2 + can also function as a stable LG, H 2 O. Compare: S N 1 solvolysis S N 1

29. Factor 5: Heat When substitution and elimination reactions are both favored under a specific set of conditions, it is often possible to influence the outcome by changing the temperature under which the reactions take place. All of these reactions have an E A that needs to be surmounted. Heat will accelerate the rate of all reactions; the object is not to overheat to allow higher E A reaction pathways to compete S N 1 is accelerated by heat, but competing reactions like elimination are accelerated more per unit heat!

30. Factor 5: Heat As the energy barrier increases, the percentage of molecules decreases. As the temperature increases, the percentage of molecules increases. In general a 10 o rise in temperature will double the rate of a reaction. At a particular temperature, only a certain percentage of molecules possess enough energy to surmount an energy barrier.

31. Factor 6: Stereochemistry of S N 1 If an S N 1 reaction is carried out on a stereochemically pure substrate, then a mixture of both the R and S enantiomers is produced.

32. Factor 6: Stereochemistry of S N 1 The mechanism explains why the reaction produces both configurations of the stereocenter. In the first step of the mechanism, Cl ⁻ simply departs, leaving behind a planar carbocation.

33. Factor 6: Stereochemistry of S N 1 If the intermediate contains a plane of symmetry, then one side of the carbocation is the mirror image of the other and approach from either side of the plane is equally likely. The product of an S N 1 reaction is always racemic at the carbon center

34. Summary S N 1 S N 2 S N 1 E1 E2 Optimize S N 2 rate: Factor 1: CH 3 >1 o >2 o ; never 3 o Factor 2: Strong, small Nu: Factor 3: Good LG/weak CB Factor 4: Polar aprotic solvent Factor 5: D S = 0 Factor 6: Stereospecific Optimize S N 1 rate: Factor 1: 3 o >2o; never 1 o , CH 3 Factor 2: Any Nu: Factor 3: Good LG/weak CB Factor 4: Polar protic solvent Factor 5: D S = 0 Factor 6: Non- stereospecific