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week 2 - 4 - anno - Chemistry S-20ab Chemistry E-2a:...

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Unformatted text preview: Chemistry S-20ab Chemistry E-2a: Lecture 6 Week 2 October 30, 2008 Elimination: The E2 Reaction • Here is an example of an E2 reaction. Can you draw a curved-arrow mechanism? C2H5O Na + H3C Ph H Br H Ph H3C Ph H + C2H5OH + Na Br Ph sodium ethoxide • Examine the stereochemistry of the above reaction. Why is this an example of antielimination? • What transition state and product would lead to syn-elimination? • What would be the rate law for this reaction? Reading: Section 9.5 13 113 Chemistry S-20ab Chemistry E-2a: Lecture 6 Week 2 October 30, 2008 Frontier Orbitals in the E2 Reaction • Let’s take a close look at the frontier orbitals involved in the E2 reaction. There are in fact two important interactions: H3C Ph H Br H Ph • Note the contrast between anti- and syn-elimination: FMO considerations donor orbital - ! C–H acceptor orbital - !* C–Br anti transiton state H3C Ph H Br H Ph syn transiton state H H3C Ph Br H Ph donor acceptor donor acceptor best overlap poor overlap Reading: Section 9.5 14 114 Chemistry S-20ab Chemistry E-2a: Lecture 6 Week 2 October 30, 2008 Alkene Isomers Formed by the E2 Reaction • Many E2 reactions can give more than one possible isomer. Can you explain the distribution of products in the following reaction? KOEt Br + 41% 14% + 25% EtOH • You may notice that the above percentages do not add to 100%. What do you suppose is the other product that emerges from the above reaction? • The choice of base can affect the distribution of products. For example: Br KOEt EtOH 71% + 29% Br KOtBu tBuOH + 28% 72% Reading: Section 9.5 15 115 Chemistry S-20ab Chemistry E-2a: Lecture 6 Week 2 October 30, 2008 E2 vs. SN2: The “GFP” Reaction Hierarchy • To help decide which reaction will predominate, apply the “GFP” (good-fair-poor) reaction hierarchy. If all else is equal, choose the reaction that is at the top of the list: 1. SN2 reactions: Require good steric interactions Good if the halide is methyl or 1° Fair if the halide is 2° Poor if the halide is 3° or if the nucleophile is very bulky (e.g. tBuO–) 2. E2 reactions: Require a strong base Good if the base is at least as strong as OH– Fair if the base is between H2O and OH– in strength Poor if the base is weaker than H2O • Let’s see some examples: Determine the primary product (and identify possible secondary products) for each of the following reactions: CH3I + OH– CH3I + O– Br + OH– Br + CN– Br + O– Br + OH– Br + CN– Reading: Section 9.5 16 116 Chemistry S-20ab Chemistry E-2a: Lecture 6 Week 2 October 30, 2008 Reactions Involving Carbocations: SN1 and E1 • Consider the following reaction. Why is it unlikely that this reaction proceeded by either an SN2 or E2 mechanism? Br EtOH 25°C O + 81% 19% • Can you propose a mechanism for this reaction? Hint: the rate law for this reaction is simply: rate = k[tBuBr] • What do you suppose is a requirement for this reaction? Reading: Section 9.6 17 117 Chemistry S-20ab Chemistry E-2a: Lecture 6 Week 2 October 30, 2008 The Stereochemistry of the SN1 Reaction • Given that the SN1 mechanism proceeds through a carbocation intermediate, what would you expect to find when you subject the following alkyl halide to SN1 conditions: H Cl H OH HO H H 2O + S S R • In fact, the products are: 33% S and 67% R. How can we explain this observation? • Can we make any generalizations about the stereochemical outcome of SN1 reactions? Reading: Section 9.6 18 118 Chemistry S-20ab Chemistry E-2a: Lecture 6 Week 2 October 30, 2008 SN1 vs. E1 Reactions • In general, whenever SN1 and E1 reactions take place, a mixture of both mechanisms is observed. Why might this be the case? • Br It is often the case that higher temperatures favor elimination. For instance: EtOH O + at 25°C: at 55°C: 81% 72% 19% 28% • One can ensure elimination by starting with an alcohol, instead of an alkyl halide, and treating it with concentrated sulfuric acid. Can you propose a mechanism for this reaction? Does this mechanism resemble any mechanism you have seen before? OH H2SO4 Reading: Section 9.6 19 119 Chemistry S-20ab Chemistry E-2a: Lecture 6 Week 2 October 30, 2008 SN1 / E1 / SN2 / E2: The “GFP” Hierarchy Revisited • We can now extend the hierarchy to include SN1 and E1 reactions: 1. SN2 reactions: Require good steric interactions Good if the halide is methyl or 1° Fair if the halide is 2° Poor if the halide is 3° or if the nucleophile is very bulky (e.g. tBuO–) 2. E2 reactions: Require a strong base Good if the base is at least as strong as OH– Fair if the base is between H2O and OH– in strength Poor if the base is weaker than H2O 3. SN1 / E1 reactions: Require a stable carbocation Good if the halide is 3° Fair if the halide is 2° Poor if the halide is methyl or 1° (Note that SN1 and E1 reactions almost always occur together, although you can ensure elimination by treating an alcohol with concentrated H2SO4.) • Use the hierarchy to determine the primary product (and identify possible secondary products) for each of the following reactions: Br + CN– Br + OH– Br + H 2O + OH– Br Br + CH3OH OH + H2SO4 Reading: Section 9.7 20 120 Chemistry S-20ab Chemistry E-2a: Lecture 6 Week 2 October 30, 2008 Carbenes and Carbenoids: Alpha-Elimination • When choroform is treated with strong base, dichlorocarbene (:CCl2) is formed. Can you write a curved-arrow mechanism for this reaction? Cl H C Cl KOtBu Cl C Cl Cl • Identify the structure, hybridization, and frontier orbitals in dichlorocarbene. • When CH2I2 is treated with a zinc-copper couple (Zn-Cu), the Simmons-Smith reagent I–CH2–ZnI is formed. This reagent is similar to a Grignard reagent. What are the frontier orbitals in the Simmons-Smith reagent? Why is this species called a carbenoid? Reading: Section 9.8 21 121 Chemistry S-20ab Chemistry E-2a: Lecture 6 Week 2 October 30, 2008 Reactions of Carbenes with Alkenes • Carbenes react with alkenes in a reaction that is highly reminiscent of the reaction of bromine with alkenes. Draw in the curved-arrow mechanisms and predict the products of each of the following: Br Br OAc Hg OAc CCl2 I IZn CH2 • What structures are formed by the addition of carbenes (or carbenoids) to alkenes? Reading: Section 9.8 22 122 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 2 November 13, 2008 Test Yourself Now! • Determine the primary product and identify any secondary products for each of the following reactions: Br + CN– Br + OH– Br + H 2O + OH– Br Br + CH3OH OH + H2SO4 1 123 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 3 2 November 13, 2008 Dehydration of Alcohols • Predict the product and show a mechanism for each of the following reactions: OH conc. H3PO4 conc. H2SO4 OH Reading: Section 10.1 2 124 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 3 2 November 13, 2008 Making Alcohols Leave: Part 1–The Problem • Explain why each of the following reactions is not effective: OH NaBr Br does NOT work OH NaOCH3 O CH3 does NOT work Reading: Section 10.2 3 125 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 3 2 November 13, 2008 Making Alcohols Leave: Part 2–Using Acid • We can convert an alcohol into a good leaving group by protonating the alcohol in strong acid. Let’s see how this works: OH conc. HBr Br OH conc. HI I Reading: Section 10.2 4 126 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 32 November 13, 2008 Making Alcohols Leave: Part 2–Acid Is A Problem • Strong acids are not generally useful for converting alcohols into good leaving groups. What is the problem with each of the following reactions? conc. HBr does NOT work OH Br OH HCN CN does NOT work OH HCl Cl does NOT work Reading: Section 10.2 5 127 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 3 2 November 13, 2008 Making Alcohols Leave: Part 3–Using Tosylates • Show the mechanism for the following reaction, in which an alcohol is converted into a good leaving group known as a tosylate: O TsCl = OH Cl S O CH3 = ClSO2R OTs pyridine = N • What can we do with a tosylate? Reading: Section 10.3 6 128 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 32 November 13, 2008 Making Alcohols Leave: Part 3–Reactions of Tosylates • For each of the following reactions, predict the product and show stereochemistry: OH TsCl pyr NaBr OH TsCl pyr NaCN OH TsCl pyr NaOEt Reading: Section 10.3 7 129 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 32 November 13, 2008 Making Alcohols Leave: Part 4–SOCl2 and PBr3 • Provide complete curved-arrow mechanisms for the following reactions: OH SOCl2, pyridine Cl OH PBr3 Br Reading: Section 10.3 8 130 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 3 2 November 13, 2008 Making Alcohols Leave: Part 4–Stereochemistry • For each of the following reactions, predict the product and show stereochemistry: OH SOCl2 pyr NaI acetone OH PBr3 NaCN • What reagents are needed to carry out the following transformations? OH Cl 1. 2. OH Br 1. 2. OH 1. 2. Reading: Section 10.3 9 131 ...
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This note was uploaded on 07/21/2010 for the course CHEM S20ab taught by Professor Mccarty during the Summer '10 term at Harvard.

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