Advanced Organic Chemistry Chapter 1 Part B PDF

Advanced Organic Chemistry Chapter_1_PART B MSC Students Dima Sabbah, Ph.D. Fall 2014  Oxidation and Reduction Introduction: Oxidation results in an increase in the number of bonds between C and a more electronegative atom, C —Z, (usually C —O) or decrease i...

Advanced Organic Chemistry Chapter_1_PART B MSC Students Dima Sabbah, Ph.D. Fall 2014  Oxidation and Reduction Introduction: Oxidation results in an increase in the number of bonds between C and a more electronegative atom, C —Z, (usually C —O) or decrease in the number of C—H bonds. Reduction results in a decrease in the number of C—Z bonds (usually C—O) or an increase in the number of C—H bonds. Figure 12.1 A general scheme for the oxidation and reduction of a carbon compound 2  Oxidation and Reduction Introduction: Two carbon atoms may be involved in a single oxidation or reduction reaction. The conversion of an alkyne to an alkene, or an alkene to an alkane are examples of this type reduction because each process adds two new C—H bonds to the starting material. Figure 12.2 Oxidation and reduction of hydrocarbons 3  Oxidation and Reduction Reducing Agents: There are three ways of introducing 2 Hs in a reduction. 1. The first method uses H2 gas. Catalytic hydrogenation requires a metal catalyst (usually Pt, Pd or Ni) with H2. 2. A second method adds two protons and two electrons to a substrate, and 2H+ + 2e- = H2 Reductions of this sort use alkali metals as a source of electrons, and liquid ammonia as a source of protons, Nao in NH3 (liq) or Lio in NH3 (liq). These are called dissolving metal reductions. 4  Oxidation and Reduction Reducing Agents: 3. The third way is to add hydride (H¯) and a proton (H+). The most common hydride reducing agents contain a hydrogen atom bonded to boron or aluminum. Simple examples include sodium borohydride (NaBH4) and lithium aluminum hydride (LiAlH4). NaBH4 and LiAlH4 deliver H¯ to the substrate, and then a proton is added from H2O or an alcohol. 5  Oxidation and Reduction Reduction of Alkenes: Catalytic Hydrogenation The addition of H2 occurs only in the presence of a metal catalyst, and thus it is called catalytic hydrogenation. The catalyst consists of a metal, usually Pd, Pt, or Ni, adsorbed onto a finely divided inert solid, such as charcoal. H2 adds in a syn fashion. 6  Oxidation and Reduction Reduction of Alkenes: Catalytic Hydrogenation The Ho of hydrogenation, also known as the heat of hydrogenation, can be used as a measure of the relative stability of two different alkenes that are hydrogenated to form the same alkane. When hydrogenation of two alkenes gives the same alkane, the more stable alkene has the smaller heat of hydrogenation. 7  Oxidation and Reduction Reduction of Alkenes: Catalytic Hydrogenation 8  Oxidation and Reduction Reduction of Alkenes: Catalytic Hydrogenation The mechanism explains two facts about hydrogenation: 9  Oxidation and Reduction Reduction of Alkenes: Catalytic Hydrogenation When unsaturated vegetable oil is treated with hydrogen, some or all of the  bonds add H2. This increases the melting point of the oil. Margarine is prepared by partially hydrogenating vegetable oils to give a product with a consistency that more closely resembles butter. Figure 12.4 Partial hydrogenation of the double bonds in a vegetable oil 10  Oxidation and Reduction Reduction of Alkynes: There are three paths to add H2 to a triple bond: 11  Oxidation and Reduction Alkyne reduction to an Alkane: Alkane formation from two successive additions: 12  Oxidation and Reduction Alkyne reduction to a Cis Alkene: Palladium metal is too reactive to allow hydrogenation of an alkyne to stop after one equivalent of H 2 adds. To stop at a cis alkene, a less active Pd catalyst is used, Pd adsorbed onto CaCO3 with added lead(II) acetate and quinoline. This is called Lindlar’s catalyst. Compared to Pd metal, the Lindlar catalyst is deactivated or “poisoned”. With the Lindlar catalyst, one equivalent of H 2 adds to an alkyne to form the cis product. The cis alkene product is unreactive to further reduction. 13  Oxidation and Reduction Alkyne reduction to a Cis Alkene: Reduction of an alkyne to a cis alkene is a stereoselective reaction, because only one stereoisomer is formed. Remember, one can also use hydroboration-acidification instead of Lindlar’s catalyst to get a cis alkene. 14  Oxidation and Reduction Alkyne reduction to a Trans Alkene: Dissolving metal reduction of a triple bond with Na in NH3 is a stereoselective reaction because it forms a trans product exclusively. Dissolving metal reductions always form the more stable trans product preferentially. The trans alkene is formed because the vinyl carbanion intermediate that is formed is more stable when the larger R groups are further away from each other to avoid steric interactions. Protonation of this anion leads to the more stable trans adduct. 15  Oxidation and Reduction Alkyne reduction to a Trans Alkene: 16  Oxidation and Reduction Alkyne reduction to a Trans Alkene: In a dissolving metal reduction (such as Na in NH3), the elements of H2 are added in an anti fashion to form a trans alkene. Na has only one electron, so, electrons for the reduction are added sequentially from 2 Na atoms. 17  Oxidation and Reduction Summary of Alkyne Reductions: Figure 12.5 Summary: Three methods to reduce a triple bond 18  Oxidation and Reduction Reduction of Polar C—X  Bonds: Alkyl halides can be reduced to alkanes with LiAlH4. Epoxide rings can be opened with LiAlH4 to form alcohols. Figure 12.6 Examples of reduction of C – X σ bonds with LiAIH4 19  Oxidation and Reduction Reduction of Polar C—X  Bonds: This reaction follows an SN2 mechanism. Unhindered CH3X and 1° alkyl halides are more easily reduced than more substituted 2° and 3° halides. In unsymmetrical epoxides, nucleophilic attack of H¯ (from LiAlH4) occurs at the less substituted carbon atom. 20  Oxidation and Reduction Oxidizing Agents: There are two main categories of oxidizing agents: 1. Reagents that contain an oxygen-oxygen bond 2. Reagents that contain metal-oxygen bonds Oxidizing agents containing an O—O bond include O 2, O3 (ozone), H2O2 (hydrogen peroxide), (CH3)3COOH (tert-butyl hydroperoxide), and peroxyacids. Peroxyacids (or peracids) have the general formula RCO3H. Figure 12.7 Common peroxyacids 21  Oxidation and Reduction Oxidizing Agents: The most common oxidizing agents with metal-oxygen bonds contain either chromium +6 (six Cr—O bonds) or manganese +7 (seven Mn—O bonds). Common Cr6+ reagents include CrO3 and sodium or potassium dichromate (Na2Cr2O7 and K2Cr2O7). Pyridinium chlorochromate (PCC) is a more selective Cr6+ oxidant. The most common Mn7+ reagent is KMnO4 (potassium permanganate). Other oxidizing agents that contain metals include OsO4 (osmium 22 tetroxide) and Ag2O [silver(I) oxide].  Oxidation and Reduction Oxidizing Agents: Figure 12.8 Oxidation reactions of alkenes, alkynes, and alcohols 23  Oxidation and Reduction Epoxidation: Epoxidation is the addition of a single oxygen atom to an alkene to form an epoxide. Epoxidation is typically carried out with a peroxyacid. 24  Oxidation and Reduction Epoxidation: Epoxidation occurs via syn addition of an O atom to either side of a planar double bond. Thus, a cis alkene gives an epoxide with cis substituents. A trans alkene gives an epoxide with trans substituents. Epoxidation is stereospecific because cis and trans alkenes yield different stereoisomers as products. 25  Oxidation and Reduction Dihydroxylation: Dihydroxylation is the addition of two hydroxy groups to a double bond, forming a 1,2-diol or glycol. Depending on the reagent, the two new OH groups can be added to the opposite sides (anti addition) or the same side (syn addition) of the double bond. 26  Oxidation and Reduction Anti-Dihydroxylation via an epoxide: Anti dihydroxylation is achieved in two steps: epoxidation, followed by ring opening with ¯OH or H3O+. 27  Oxidation and Reduction Syn Dihydroxylation: Syn hydroxylation results when an alkene is treated with either KMnO4 or OsO4. dilute The reaction of an alkene or an alkyne with dilute KMnO4 is the Baeyer test for unsaturation. KMnO4 and the MnO2 product is a brown precipitate. 28  Oxidation and Reduction Syn Dihydroxylation: Each reagent adds two oxygen atoms in a syn fashion. Hydrolysis of the cyclic intermediate cleaves the metal oxygen bonds, forming a cis-1,2-diol. 29  Oxidation and Reduction Syn Dihydroxylation: Dihydroxylation can also be carried out by using a catalytic amount of OsO4, if either the oxidant N-methylmorpholine N-oxide (NMO) or hydrogen peroxide is also added. In the catalytic process, dihydroxylation of the double bond converts the Os8+ oxidant into an Os6+ product, which is then reoxidized by NMO or H2O2 to Os8+. or H2O2 30