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week 2 - 5 - anno - Chemistry S-20ab Chemistry E-2a:...

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Unformatted text preview: 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 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 3 2 November 13, 2008 Oxidation of Alcohols • Alcohols can be oxidized with various oxidizing agents. The most common are various derivatives of CrO3. We can make the following general observations: For primary alcohols: O CrO3 ("dry") OH H O CrO3 ("wet") OH OH (Where else have you seen an “option” for forming aldehydes versus forming carboxylic acids?) For secondary alcohols: OH O CrO3 What do you think will happen for tertiary alcohols? OH CrO3 ??? Reading: Sections 10.5 and 10.6 10 132 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 32 November 13, 2008 Oxidation of Alcohols: Mechanisms • Draw curved-arrow mechanisms for each of the following steps in the oxidation of isopropanol: OH O CrO3H + CrO3 H O CrO3H + H 3O + O + H3O+ + H2CrO3 Reading: Section 10.6 11 133 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 32 November 13, 2008 Oxidation of Primary Alcohols to Carboxylic Acids • In water, the oxidation of primary alcohols proceeds beyond the aldehyde stage and ends up with a carboxylic acid. Provide a mechanism for these steps: Initial oxidation (same as on previous page): CrO3 OH H O Subsequent reactions: H O H + H3O+ HO OH + H+ H OH HO H + CrO3 HO O CrO3H H O HO CrO3H + H 3O + HO O + H3O+ + H2CrO3 Reading: Section 10.6 12 134 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 32 November 13, 2008 Reduction of Aldehydes and Ketones • Aldehydes and ketones can be reduced to alcohols using NaBH4. We will not discuss the mechanism of this reaction at this point; you should simply be aware that this reaction gives exactly the reverse of the oxidation reactions discussed above: Interconversion of primary alcohols and aldehydes: O CrO3 ("dry") OH H O NaBH4 H OH Interconversion of secondary alcohols and ketones: OH O CrO3 O OH NaBH4 Reading: Section 19.8 (no, that’s not a typo!) 13 135 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 32 November 13, 2008 Thiols vs. Alcohols: Similarities • The following reactions show some of the similarities between thiols and alcohols. Can you draw curved-arrow mechanisms for each step? NaH OH O– Br O NaOH SH S– Br S • Compare alkoxides with thiolates. Which will be better nucleophiles, and why? Reading: Section 11.1 16 138 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 32 November 13, 2008 Thiols vs. Alcohols: Differences • Oxidation of thiols proceeds quite differently from oxidation of alcohols. In particular, it is the sulfur that is oxidized, rather than the carbon. • Draw a curved-arrow mechanism for the following oxidation of thiols to disulfides: NaOH, I2 SH S S • Vigorous oxidation of thiols yields sulfonic acids. (No need to know the mechanism) HNO3 SH O S OH O Reading: Section 10.9 17 139 Chemistry S-20ab Chemistry E-2a: Lecture 7 Week 32 November 13, 2008 Putting It Together: Synthesis • Propose a synthetic route to the following desired product from the indicated starting material. All of the carbon atoms from the starting material must end up in your product. Starting Material: OH Cl Desired Product 18 140 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Test Yourself Now! Using only alcohols as starting materials, synthesize the following product: O 1 141 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Synthesis of Ethers 1: Williamson Ether Synthesis • You already know all of the routes for synthesizing ethers! Let’s take a look at the following problem: Using only alcohols as starting materials, synthesize the following ether: O Reading: Section 11.1 2 142 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Synthesis of Ethers 2: Alkoxymercuration-Reduction • What would happen if you tried a “Williamson” route to synthesize the following ether? O • Is there another way to synthesize that ether? Use only alcohols as starting materials. O Reading: Section 11.1 3 143 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Synthesis of Ethers 3: Routes Involving Carbocations • Write complete curved-arrow mechanisms for the following reactions, each of which produces the ether MTBE (methyl-tert-butyl ether), which has been used as a gasoline additive: H+ cat. + H3C OH O CH3 H+ cat. + OH H3C OH O CH3 Reading: Section 11.1 4 144 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Cleavage of Ethers • Ethers are generally inert under most reaction conditions; they are often used as solvents. However, ethers can be cleaved under certain conditions. Draw curved-arrow mechanisms for the following reactions: O HBr (conc.) heat Br Br O HCl Cl + HO Reading: Section 11.3 5 145 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Cyclic Ethers and Epoxides • HO Draw a curved-arrow mechanism and predict the product of the following reactions: Br NaOH Br HO NaOH • The three-membered cyclic ether is given the special name epoxide. Why might this epoxide exhibit reactivity different from that of the 5-membered ring above? Reading: Section 11.2 6 146 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 3 2 November 20, 2008 Synthesis of Epoxides With Halohydrins • Provide complete curved-arrow mechanisms for each step in the following transformation. Be sure to pay attention to stereochemistry! Br2 , H2O OH NaOH O Br (+/–) (+/–) • Explain why the following halohydrin cannot be transformed into an epoxide: OH NaOH no reaction Br Reading: Section 11.2 7 147 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Synthesis of Epoxides With Peroxycarboxylic Acids • A much more convenient, one-step synthesis of epoxides from alkenes uses peroxycarboxylic acids, often called “peracids.” Some examples: O O R O H O O O H a general peracid Cl mCPBA meta-chloroperoxybenzoic acid • Draw the curved arrows for the following single-step synthesis of an epoxide from an alkene: R O O H O O H O R O • Identify the molecular orbitals involved in this reaction. Is this mechanism similar to any other reactions you have seen before? Reading: Section 11.2 8 148 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Opening Epoxides: Acidic Conditions • Provide a mechanism and explain why the indicated product is formed selectively in each of the following reactions: O CH3 mCPBA O CH3OH H+ (+/–) (+/–) OH Reading: Section 11.4 9 149 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Opening Epoxides: Basic Conditions • Provide a mechanism and explain why the indicated product is formed selectively in each of the following reactions: mCPBA O O CH3 NaOCH3 OH (+/–) (+/–) Reading: Section 11.4 10 150 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Opening Epoxides with Grignard Reagents • Provide a mechanism that shows how the following epoxide reacts with the indicated Grignard reagent: OH mCPBA O CH3MgBr H+ workup CH3 • This reaction is quite useful for synthesis, because it forms a new carbon-carbon bond. Provide a synthetic route for the following transformation: OH OH Reading: Section 11.5 11 151 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Synthesis of Glycols (Vicinal Diols) from Epoxides • Glycols can be synthesized from epoxides. What is the overall stereochemistry of the following transformation? mCPBA O OH H3O+ OH (+/–) (+/–) • O H– + In general, acid-catalyzed hydrolysis of epoxides is preferable to base-catalyzed hydrolysis, because base-catalyzed hydrolysis can result in polymerization: O HO O O O– etc. This polymerization reaction is extremely exothermic, and can be dangerous! Reading: Section 11.5 12 152 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Synthesis of Glycols (Vicinal Diols) from Alkenes • There is a direct route to synthesis of glycols from alkenes using osmium tetroxide, OsO4. Draw the curved arrows for the following reaction. What is the overall stereochemistry of this reaction? O Os O O O = OsO4 OsO4 O Os O O O H2O OH OH (+/–) (not isolated) (+/–) Reading: Section 11.5 13 153 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Cleavage of Glycols: It!s Kinda Like Ozonolysis • Glycols react with HIO4 (periodic acid . . . how do you pronounce that?) to give products in which the C–C bond of the glycol has been cleaved: CH3 OsO4 OH OH HIO4 O O H O = H O CH3 • Is this overall transformation reminiscent of anything? Reading: Section 11.5 14 154 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Sulfides and Sulfonium Salts • The sulfur of a sulfide (“thioether”) is a reasonably good nucleophile—much better than the oxygen of an ether. Thus, sulfides can be SN2 nucleophiles. The resulting products are called sulfonium salts: S + Br S Br • In my doctoral research, I wanted to carry out a reaction similar to the following. Draw the Lewis structure for the sulfite (SO32–) ion and provide a curved-arrow mechanism. Cl Na2SO3 H2O SO3– Na+ + NaCl • The above reaction did not work because the starting material was totally insoluble in water, and the sodium sulfite was only soluble in water. To solve this problem, I first reacted the alkyl chloride with dimethyl sulfide (yuck!) to form a sulfonium salt. The sulfonium salt, being an ionic compound, was soluble in water and reacted readily to give the desired product: Cl Me2S Me S Me Na2SO3 H2O SO3– Na+ + NaCl + Me2S Cl Reading: Section 11.6 15 155 Chemistry S-20ab Chemistry E-2a: Lecture 8 Week 32 November 20, 2008 Neigboring-Group Participation • When an alkyl halide has a nucleophilic atom (often S or N) nearby in the same molecule, the molecule can undergo an intramolecular SN2 reaction that may then be followed by an intermolecular SN2 reaction! What product would you expect to be formed by the following reaction: (Include a curved-arrow mechanism) S OH • HBr • The actual product is shown below. Draw a curved-arrow mechanism that can account for the unusual product. (Note that this is not a simple methyl shift!) S OH HBr S Br • What is one experiment you could do to prove that this mechanism is not a simple methyl shift? Reading: Section 11.7 16 156 Chemistry S-20ab Chemistry E-2a: Lecture 9 Week 3 2 December 11, 2008 Test Yourself Now! Provide a complete synthesis of the desired product from the indicated starting material. You may use any organic or inorganic reagents in your synthesis. OH OH HO 1 157 ...
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