Advanced Organic Chemistry Chapter 1 Part C PDF

Advanced Organic Chemistry Chapter_1_PART C MSC Students Dima Sabbah, Ph.D. Fall 2020  Oxidation and Reduction Oxidative Cleavage of Alkenes with KMnO4: Addition of conc. KMnO4 in base with heat to an alkene results in cleavage between the carbons of the double bo...

Advanced Organic Chemistry Chapter_1_PART C MSC Students Dima Sabbah, Ph.D. Fall 2020  Oxidation and Reduction Oxidative Cleavage of Alkenes with KMnO4: Addition of conc. KMnO4 in base with heat to an alkene results in cleavage between the carbons of the double bond. Products depend on the number of hydrogens attached to each carbon of the alkene. Look at each C. R-CH=CH2 One H on C yields a carboxylic acid, RCOOH Two Hs on C yields carbon dioxide, CO2 R-CH=CH-R' One H on C yields a carboxylic acid, RCOOH + R'COOH R2-C=CH2 No Hs on C yields a ketone, R-CO-R Two Hs on C yields carbon dioxide, CO2 2  Oxidation and Reduction Oxidative Cleavage of Alkenes with O3: Oxidative cleavage of an alkene breaks both the  and  bonds of the double bond to form two carbonyl compounds. Cleavage with ozone (O3) is called ozonolysis. 3  Oxidation and Reduction Oxidative Cleavage of Alkenes with O3: Addition of O3 to the  bond of an alkene forms an unstable intermediate called a molozonide, which rearranges to an ozonide in a stepwise process. The unstable ozonide is reduced to afford carbonyl compounds. Zn (in H2O) or dimethylsulfide (CH3SCH3) are two common reagents used to convert the ozonide into carbonyl compounds. 4  Oxidation and Reduction Oxidative Cleavage of Alkenes with O3: Ozonolysis of dienes or other polyenes results in oxidative cleavage of all C=C bonds. It is important to note that when oxidative cleavage involves a double bond that is part of a ring, the ring opens up affording a single chain with two carbonyls at the carbons where the double bonds were originally. 5  Oxidation and Reduction Oxidative Cleavage of Alkynes with O3: Alkynes undergo oxidative cleavage of the  and both  bonds. Internal alkynes are oxidized to carboxylic acids (RCOOH). Terminal alkynes afford a carboxylic acid and CO 2 from the sp hybridized C—H bond. 6  Oxidation and Reduction Oxidation of Alcohols: Alcohols are oxidized to a variety of carbonyl compounds. 7  Oxidation and Reduction Oxidation of Alcohols: Recall that the oxidation of alcohols to carbonyl compounds is typically carried out with Cr6+ oxidants, which are reduced to Cr4+ then to Cr3+ products. CrO3, Na2Cr2O7, and K2Cr2O7 are strong, nonselective oxidants used in aqueous acid (H2SO4 + H2O). PCC is soluble in CH2Cl2 (dichloromethane) and can be used without strong acid present, making it a more selective, milder oxidant. 8  Oxidation and Reduction Oxidation of 2° Alcohols: Any of the Cr6+ oxidants effectively oxidize 2° alcohols to ketones. 9  Oxidation and Reduction Oxidation of 1° Alcohols: 1° Alcohols are oxidized to either aldehydes or carboxylic acids, depending on the reagent. 10  Oxidation and Reduction Oxidation of 1° Alcohols: 11  Oxidation and Reduction Oxidation of 1° Alcohols: Cr6+ oxidations are characterized by a color change. The red-orange Cr6+ reagent is reduced to the green Cr3+. Some devices used to measure blood alcohol content make use of this color change: Oxidation of CH3CH2OH, the 1° alcohol in alcoholic beverages, with orange K2Cr2O7 forms CH3COOH and green Cr3+. 12  Oxidation and Reduction Oxidation of 1° Alcohols: Blood alcohol level can be determined by having an individual blow into a tube containing K2Cr2O7, H2SO4, and an inert solid. The higher the concentration of CH3CH2OH in the breath, the more Cr6+ is reduced, and the farther the green Cr3+ color extends down the length of the sample tube. The extent of the green color is then correlated with blood alcohol levels. 13  Oxidation and Reduction Oxidation of 1° Alcohols: Figure 12.10 Blood alcohol screening 14  Oxidation and Reduction Green Chemistry: Green chemistry is the use of environmentally safe or harmless methods to synthesize compounds. Its purpose is to use safer reagents and less solvent, and develop reactions that form fewer by-products and generate less waste. Since many oxidation methods use toxic reagents (such as OsO4 and O3) and corrosive acids such as H2SO4, or generate carcinogenic by-products (such as Cr3+), alternative less problematic regents have been developed. One methods uses a polymer supported Cr3+ reagent, Amberlyst A-26 resin-HCrO4, this avoids the use of strong acid, and forms a Cr3+ by-product that can easily be removed from the product by filtration. The Amberlyst A-26 resin consists of a complex hydrocarbon network with cationic ammonium ion appendages that serve as counterions to the anionic chromium agent, HCrO4¯. 15  Oxidation and Reduction Green Chemistry: Heating the insoluble polymeric reagent with an alcohol results in oxidation to a carbonyl compound, with formation of an insoluble Cr3+ by-product which can be regenerated and reused in a subsequent reaction. 16  Oxidation and Reduction Green Chemistry: With Amberlyst A-26 resin-HCrO4¯, 1° alcohols are oxidized to aldehydes and 2° alcohols are oxidized to ketones. 17  Oxidation and Reduction The Sharpless Epoxidation of allylic alcohols: Recall that in the reactions we have discussed thus far, an achiral starting material has reacted with an achiral reagent to give either an achiral product, or a racemic mixture of two enantiomers. 18  Oxidation and Reduction The Sharpless Epoxidation: The Sharpless reagent consists of three different components: tert-butylhydroperoxide (CH3)3COOH; a titanium catalyst (usually titanium(IV) isopropoxide), Ti[OCH(CH3)2]4; and diethyl tartrate (DET). There are two different chiral diethyl tartrate isomers, labeled as (+)-DET or (-)-DET to indicate the direction in which they rotate plane polarized light. The identity of the DET isomer determines which enantiomer is the major product obtained in the epoxidation. 19  Oxidation and Reduction The Sharpless Epoxidation: In the Sharpless epoxidation, the double bonds of allylic alcohols are oxidized to epoxides. Since the formation of only one enantiomer is favored, the reaction is said to be enantioselective or asymmetric. An enantioselective reaction affords predominantly or exclusively one enantiomer. 20  Oxidation and Reduction The Sharpless Epoxidation: The peroxide is the oxidizing agent (1:1 with the alkene). The titanium and DET form a catalytic complex (about 5-10%). 21  Oxidation and Reduction The Sharpless Epoxidation: To determine which enantiomer is formed from a given isomer of DET, draw the allylic alcohol in a plane, with the OH group in the bottom right hand corner; then note that: 22  Oxidation and Reduction The Sharpless Epoxidation: Reactions and are highly enantioselective as each has an enantiomeric excess of 95% (i.e., 97.5% of the major enantiomer and 2.5% of the minor enantiomer). 23  Thiols (Mercaptans) Sulfur analogues of alcohols are called thiols. The —SH group is called a mercapto group. Named by adding the suffix -thiol to the alkane name. They are commonly made by an SN2 reaction so primary alkyl halides work better. Chapter 10 24  Synthesis of Thiols The thiolate will attack the carbon displacing the halide. This is an S 2 reaction so methyl halides will react N faster than primary alkyl halides. To prevent dialylation use a large excess of sodium hydrosulfide with the alkyl halide. Chapter 10 25  Thiol Oxidation Thiols can be oxidized to form disulfides. The disulfide bond can be reduced back to the thiols with a reducing agent. Chapter 10 26