Dr. Laurie S. Starkey, CHM 3140 Organic Chemistry I, Cal Poly Pomona Chapter 7 – Substitution Rxns, Part 2 – Practice Problems Some of these problems are from the Ch. 7, Part 1 skeleton notes (page). p.7-7 Cal Poly Pomona, Dr. Laurie S. Starkey, Organic Chemistry I, CHM 3140 7-12 Substitution Reactions: Leaving Groups, Nucleophiles & Solvents All Substitution and Elimination reactions need O Electrophiles with good leaving groups (LG), such as Cl-, Br-,I-, and TsO-. Substitution reactions CF3 OH trifluoro- need Nucleophiles (SN2 needs a good Nu:; SN1 acetic acid needs a weak Nu:) and Elimination reactions need Bases (E2 needs strong base; E1 needs weak base). H2O water Poor Leaving Groups (LG) CH3OH protic H2N RO HO CN N3 F methanol Good Nucleophiles (Nu:) O HO RO HS RS CH3 OH acetic acid CN N3 I Br CH3CH2OH :NH3 :NH2R R3P: ethanol CH3CN Weak Nucleophiles (Nu:) acetonitrile H2O ROH (these are also weak bases) O Strong Bases (B:) S CH H N RO HO (needed for E2) CH3 3 2 dimethyl sulfoxide (DMSO) Synthetic Utility of the SN2: NaI O I NaCN H N(CH3)2 CN Dimethylformamide NaSMe (DMF) SMe O NaOMe aprotic Cl OMe polarity) increasing power (increasing ionizing solvent CH3 CH3 NaN3 acetone N3 CHCl O 3 chloroform NaOAc O O NaOH OH tetrahydrofuran NH3 (THF) NH3 Cl PPh 3 CH CH OCH CH Cl PPh3 Cl 3 2 2 3 NaCCH diethyl ether (ether) In the box provided, indicate the mechanism involved in each of the following reactions (SN1 or SN2). If no reaction is expected, write NR. Predict the major product(s) expected, and remember to indicate stereochemistry, when appropriate. IV. SolventEffects(7.12) 7-11 Both SN1 and SN2 reactions need POLAR solvents to stabilize charges in the mechanism. Protic Aprotic - has an OH group - has no OH group - extremely polar - strongly stabilizes charges Solvent Effects on Reaction Rates if you INCREASE solvent polarity, then SN1 is ______________ and SN2 is ______________ e.g. using a protic solvent instead of an aprotic solvent e.g. going from an 80:20, EtOH:H2O solvent to 50:50 Why is a more polar solvent GOOD for an SN1 mechanism? (speeds it up) Cl H2O OH Cl - carbocation will be better stabilized by more polar solvent polar aprotic - C+ intermediate and transition state are more stable/lower E - Ea (lower height of hill), rate of reaction E POR -SN1 is FASTER in a more polar solvent Why is a more polar solvent BAD for an SN2 mechanism? (slows it down) Br HO OH Br polar aprotic - nucleophile will be better stabilized by more polar solvent - Nu: is more stable, less reactive E - Ea (increased height of hill), rate of reaction -S 2 is SLOWER in a more polar solvent N POR Cal Poly Pomona, Organic Chemistry I, CHM 3140, Dr. Laurie S. Starkey Comparison of SN1 and SN2 Mechanisms S 1 or Consider a RX + Nu:N RNu + X S 2 substitution Alkyl Halide NucleophileN Leaving Group reaction: Electrophile (E+) (LG) SN1 SN2 both SN1&SN2 Categorize each of the following items as being related to SN1, SN2, or both. carbocation sterics no reaction strong Nu: on vinyl RX bimolecular aprotic solvent Rate = k[RX][Nu:] HO- Nu: unimolecular t-BuBr = fastest good LG Rate = k[RX] H O Nu: 2 no reaction MeOH Nu: solvolysis weak Nu: on 3º RX backside attack MeI = fastest inversion of rearrangement stereochemistry a bond forms in no reaction a bond breaks in rate-determining step on 1º RX NaOMe Nu: rate-determining step more than one unhindered E+ racemization transition state protic solvent only one 1º RX 3º RX transition state 2º RX.