Chapter 18: Ethers and Epoxides; Thiols and Sulfides, Schemes and Mind Maps of Geometry

Download Chapter 18: Ethers and Epoxides; Thiols and Sulfides and more Schemes and Mind Maps Geometry in PDF only on Docsity! 57 112 Chapter 18: Ethers and Epoxides; Thiols and Sulfides O R H O R R O alcohols ethers epoxides CH3CH2OCH2CH3 O OCH3 thiols sulfides episulfides (mercaptans) (thioethers) unstable S R H S R R S -S CH3CH2CH2SH CH3SCH3 SH SH H2N CHC CH2 OH O SH H2N CH C CH2 OH O CH2 S CH3 113 18.1 Naming Ethers Simple ethers are named by identifying the two organic substituents and adding the word ether If other functional groups are present, the ether part is considered an alkoxy substituent 58 114 18.2: Structure & properties of ethers: The oxygen of ethers is sp3-hybridized and tetrahedral The ether oxygen is a weak Lewis base Ethers have small dipole moments and are relatively non-polar Inert to a wide range of reaction conditions- good solvents Synthesis of ethers: Symmetrical ethers can be prepared by treating the corresponding alcohol with a strong acid Limitations: must be symmetrical works best for 1° alcohols 115 18.3: Williamson Ether Synthesis Reaction of metal alkoxides with alkyl halides or tosylates to give ethers. This is an SN2 reaction. Alkoxides are prepared by the reaction of an alcohol with a strong base such as sodium hydride, NaH C OH3C CH3 CH3 H3C I THF + C OH3C CH3 CH3 CH3 C OHH3C CH3 CH3 C OH3C CH3 CH3 + NaH THF Na + NaH - H2 + NaI Na SN2 Few restriction regarding the nature of the alkoxide Works best for 1° alkyl halide or tosylate; E2 elimination is a competing reaction with 2° halides and tosylates 3° halides undergo E2 elimination (vinyl and aryl haildes do react) Br (R)-2-Bromohexane CH3CH2-O Na+ _ THF OCH2CH3 (S) 61 120 Stereochemistry of the mCPBA epoxidation: syn addition of oxygen. The geometry of the alkene is preserved in the product (recall the cyclopropanation of alkenes, Ch. 7.6) Groups that are trans on the alkene will end up trans on the epoxide product. Groups that are cis on the alkene will end up cis on the epoxide product. H H R R cis-alkene mCPBA H H R R O cis-epoxide H R R H trans-alkene H R R H O trans-epoxide CH2Cl2 mCPBA CH2Cl2 121 Intramolecular Williamson Synthesis: general method for the synthesis of cyclic ethers: the alkoxide and alkyl halide are part of the same molecule OHBr NaH, THF Br O O SN2 Epoxides from halohydrins SN2Br2, H2O Br OH NaH, THF Br O anti addition O 62 122 18.8: Ring-Opening Reactions of Epoxides Acid-catalyzed epoxide opening: protonation of the epoxide oxygen makes it more reactive toward nucleophiles hydroysis of epoxides give vicinal diols O H H mCPBA H3O + H H OH OH trans-1,2-cyclohexanediol O H H H OH2 H OH OH H cis-1,2-cyclohexanediol OsO4 NaHSO3 complementary to dihydroxylation of alkenes acid-catalyzed halohydrin formation from epoxides O H H H-X H H OH X O H H H X ether 123 Regiochemistry of acid-catalyzed epoxide openings: if the carbons of the epoxide are 1° or 2°, then the epoxide opening goes predominantly by an SN2 mechanism and the nucleophile adds to the least substituted carbon if either carbon of the epoxide is 3°, the epoxide opening goes predominantly by an SN1 mechanism and the nucleophile adds to the 3°-carbon 63 124 Nucleophilic (base-catalyzed) epoxide opening: Epoxide undergo ring-opening with nucleophiles via an SN2 mechanism Nucleophilic epoxide opening with Grignard reagents C CH2 O H3CH2C H OR C CH2 O H3CH2C H OR 100° C ROH C CH2 HO OR + RO C CH2 O H3CH2C H BrMg-CH3 CH CH2 OH H3CH2C CH3 ether then H3O+ The nucleophile will add to the least substituted carbon of the epoxide (SN2 mechanism) 125 18.9: Crown Ethers (please read) 18.10: Thiols and sulfides Thiols (mercaptans) are sulfur analogues of alcohols Sulfides (thioethers) are sulfur analogues of ethers Preparation of thiols from alkyl halides (SN2): H3C-H2C-H2C-H2C Br H2N NH2 S + H3C-H2C-H2C-H2C S NH2 NH2 HO H3C-H2C-H2C-H2C S NH2 NH2 O H H3C-H2C-H2C-H2C SH H2N NH2 O + Thiourea