Organic Chemistry

1. Organic Chemistry Chapter 8

2. Substitution and Elimination • If an sp3 C is bonded to electronegative atom Substitution reactions and Elimination reactions are possible This chapter is all about substitution

3. example SN2 and SN1 Reactions SN2 - Reaction – bonds break and form at the same time SN2 • SN1 - CX bond breaks, forming a C+ then reacts with a nucleophile SN1

4. Nucleophilic Substitution Reactions Either mechanism depends on the: • structure of the alkyl halide • reactivity of the nucleophile • concentration of the nucleophile • The solvent in which the Rx is carried out • The leaving group

5. SN2 Mechanism • It’s a Substitution Reaction (S) • It’s Nucleophilic (N) • It’s rate is second order (2) • Called bimolecular (rate is dependent on 2 reactants) • (Substitution Nucleophilic Bimolecular) Rate = k [RX] [Nu:] (Because rate is dependent of BOTH RX and Nu: it is 2nd. order.)

6. SN2 Mechanism • SN2Mechanism involves a “backside attack”

7. SN2 Mechanism The “backside attack” causes an Inversion of Configuration Careful now….. Doesn’t mean R becomes S – new atoms are involved

8. Steric Hindrance • Groups that block the path from the nucleophile to the electrophilic atom produce steric hindrance • This results in a rate differences or no reaction at all methyl halide ethyl halide isopropyl halide t-butyl halide

9. Steric Hindrance • Activation Energy is higher due to steric hindrance…..

10. Substitution Reactions Depend on a Good Leaving Group • R-F alkyl fluorides • R-Cl alkyl chlorides • R-Br alkyl bromides • R-I alkyl iodides • Alkyl Halides make good “leaving groups” • They are easily displaced by another atom • They allow the Conversion of alkyl halides to other functional groups

12. SN2 Mechanism • The Leaving Groups also affects rate • RI reacts fastest, RF slowest • Iodide is the best “leaving group” • Fluoride is the worst “leaving group” (…reacting with the same alkyl halide under the same conditions)

13. Basicity • The weaker the basicity of a group, the better the leaving ability. (Lewis base = e- pair donor) • Leaving ability depends on basicity because a weak base does not SHARE its e- as well as a strong base. • Weak bases are not strongly bonded to a carbon (weak bases are GOOD leaving groups)

14. Nucleophiles – Strong/Weak Good/Bad Stronger base Weaker base Better nucleophile poorer nucleophile OH- > H2O CH3O- > CH3OH -NH2 > NH3 CH3CH2NH- > CH3CH2NH2 (conjugate acids)

15. Nucleophiles • The strength of nucleophile depends on reaction conditions. • In the GAS phase (not usually used),direct relationship between basicity and nucleophilicity

16. Solvent Effects • In a solution phase reaction, the solvent plays a large role in how the reaction will occur • Solvent effects can cause just the opposite of what might be the expected behavior of the nucleophile • Solvents are categorized as either protic or aprotic

17. Protic Solvents Protic solvents has a H bonded to a N or O • It is a H bonder • Examples: H2O, CH3OH, NH3, etc • Solvent is attracted to the Nucleophile and hinders its ability to attack the electrophile

18. DMSO DMF Aprotic Solvents • Use an aprotic solvent • Solvates cations • Does not H bond with anions (nucleophile free) • Partial + charge is on inside of molecule • Negative charge on surface of molecule (solvates cation) • Examples include: • DMSO (dimethyl sulfoxide) • DMF (dimethyl formamide) • Acetone (CH3COCH3)

19. Question… Nucleophiles • In the organic solvent phase, INVERSErelationship between basicity and nucleophilicity with a protic solvent

20. Nucleophiles • Solvents can solvate the nucleophile • Usually this is NOT good because the nucleophile is “tied up” in the solvent and LESS REACTIVE. Ion-dipole interactions

21. Nucleophiles • Solvents can solvate the nucleophile (Methanol is a polar protic solvent.)

22. SN2 Reactions

23. SN2 Reactions

24. SN2 Reactions • SN2 reactions might be reversible • Leaving group would become the nucleophile • Compare basicity (nucleophile strength) to see which is a better leaving group. • The stronger base will displace the weaker base • If basicity is similar, the Rx will be reversible

25. SN2 Reactions Compare basicity to see which is a better nucleophile.

26. SN1

27. SN1 Reactions • Reaction of t-butyl bromide with water should be slow • water is a poor nucleophile • t-butyl bromide is sterically hindered However • Reaction is a million times faster than with CH3Br (Maybe not an SN2 reaction!)

28. SN1 Reactions

29. SN1 Mechanism • Rate determining step does not involve nucleophile Step 1 Step 2

30. SN1 Mechanism

31. SN1 Reactivity • Relative Reactivities in an SN1 Reaction 1o RX < 2o RX < 3o RX Increasing Reactivity

32. SN1 Stereochemistry • Because a planer carbocation is formed, nucleophilic attack is possible on both sides, so both isomers are possible

33. SN1 Stereochemistry • SN1 should yield racemic mixture but it doesn’t • This is due to the steric hindrance of the leaving group

34. Stereochemistry • As the leaving group goes (Marvin K) it blocks the path of any incoming nucleophiles

35. SN1 vs SN2 Inversion of configuration racemization with partial inversion

36. What Makes SN1 Reactions work the best • Good Leaving Group • The weaker the base, the less tightly it is held (I- and Br- are weak bases) • Carbocation • How stable is the resulting carbocation? • 3o > 2o > 1o > methyl Increasing Stability

37. What Doesn’t Matter In anSN1 Reactions • The Nucleophile • It has NO EFFECT on rate of Rx!!! • Solvolysis Reactions • (the nucleophile is also the solvent) Nu:

38. Carbocation Rearrangements Since a carbocation is the intermediate, you may see rearrangements in an SN1 Rx • No rearrangements in an SN2 Rx

39. Carbocation Rearrangement • Methyl Shift

40. Benzylic, Allylic, Vinylic,and Aryl Halides • Benzylic and allylic halides can readily undergo SN2 unless they are 3o • (steric hindrance)

41. Benzylic, Allylic, Vinylic,and Aryl Halides • Benzylic and allylic halides can also undergo SN1(they form stable carbocations) • Even though 1o RX do not go SN1, 1o benzylic and 1o allylic CAN react SN1!

42. Vinylic,and Aryl Halides • Vinylic halides and aryl halides • do not undergo SN1 or SN2 reactions! p e- repel incoming Nucleophile

43. SN1 vs SN2 Review

44. Methyl, 1oRX … 2oRX … 3oRX … Vinylic, aryl RX … 1o, 2o benzylic, allylic RX … 3o benzylic, allylic RX … SN2 only SN1 and SN2 SN1 only neither SN1 nor SN2 SN1 and SN2 SN1 only SN1 vs SN2

45. In an SN1, a carbocation and halide ion are formed Solvation provides the energy for X- being formed In SN1 the solvent “pulls apart” the alkyl halide SN1 cannot take place in a nonpolar solvent or in the gas phase Increasing the polarity of the solvent will INCREASE the rate of Rx if none of the REACTANTS are charged. If reactants are charged it will DECREASE the rate. Role of the Solvent

46. So…. In an SN1 reaction, the reactant is RX. The intermediate is charged and is STABILIZED by a POLAR solvent A POLAR solvent increases the rate of reaction for an SN1 reaction. Role of the Solvent (However, this is true only if the reactant is uncharged.)

47. *

48. In an SN2 reaction, one of the reactants is the nucleophile (usually charged). The POLAR solvent will usually stabilize the nucleophile. A POLAR solvent decreases the rate of reaction for an SN2 reaction. Role of the Solvent In SN2 (However, this is true only if the nucleophile is charged.)

49. Polar Aprotic Solvents include: DMF N,N-dimethylformamide DMSO dimethylsulfoxide HMPA hexamethylphosphoramide THF Tetrahydrofuran And even… acetone Polar Aprotic Solvents

50. Polar Aprotic Solvents do not H bond solvate cations well do NOT solvate anions (nucleophiles) well good solvents for SN2 reactions Polar Aprotic Solvents