Chapter 16 Ether Epoxides and Sulfides 1 Ethers Epoxides and Sulfides Ethers are relatively unreactive Epoxides are very reactive Sulfide reactivity is compared to that of ethers 2 IUPAC Nomenclature Ethers In substitutive naming the smaller alkyl group is an alkoxy substituent Substitutive name Functional name ethoxyethane diethylether methoxyethane 3 chloro 1 ethoxypropane ethyl methyl ether 3 chloro 1 propyl ethyl ether Cyclic ethers Substitutive name oxirane oxetane Functional name etheylene oxide oxolane tetrahydrofuran oxane tetrahydropyran 3 IUPAC Nomenclature Ethers and Sulfides Compounds with Multiple Ether Linkages Sulfides 4 Structure of Ethers Bond angles increase with increasing van der Waals strain and bulky group introduces more steric strain Conformations of ethers are similar to alkanes the effect of O is similar to a CH2 group 5 Structure of Epoxides Epoxides are severely strained since the sp3 carbons prefer tetrahedral bond angles 6 Physical Properties of Ethers Alcohols have high boiling points due to hydrogen bonding Ethers have weaker dipole dipole interactions and boiling points are similar to alkanes 7 Physical Properties of Ethers Ethers can hydrogen bond to water so small ethers are fairly soluble in water The electrostatic potential map of ether water and hydrogen bonded complex are shown 8 Physical Properties of Ethers 9 Physical Properties of Ethers Widely used as solvents Can dissolve nonpolar and polar substrates Unreactive towards strong bases 10 Crown Ethers Macrocyclic polyethers are named crown ethers based on their 3 D structure The name crown is preceded by the number of atoms in the ring and followed by the number of oxygen atoms 11 Crown Ethers Bind group 1 cations Which cation depends on size of crown ether Salts can be dissolved in nonpolar organic solvents for SN2 reactions 12 Crown Ethers Electrostatic potential map shows electron rich core left Space filling model shows complexation with K right 13 Crown Ethers Polyether antibiotic Monesin binds sodium ion 14 Preparation of Ethers Acid catalyzed dehydration of alcohols yield symmetrical ethers Acid catalyzed addition of alcohols to alkenes yields ethers 15 Williamson Ether Synthesis Nucleophilic substitution reaction SN2 on unhindered primary halides or tosylates Alkoxide is commonly made by adding Na K or NaH to the corresponding alcohol 16 Williamson Ether Synthesis Nucleophilic substitution reaction Examples 17 Ether Oxidation in Air Ethers are readily oxidized to peroxides 18 Acid Catalyzed Cleavage of Ethers Reaction may occur with one or two equivalents of a hydrogen halide ROR HX RX R OH ROR 2 HX RX R X H2O 19 Acid Catalyzed Cleavage of Ethers Mechanism Reaction equation Step 1 Protonation Step 2 Nucleophilic Attack 20 Acid Catalyzed Cleavage of Ethers Mechanism Reaction equation Step 3 Protonation Step 4 Nucleophilic Attack 21 Sharpless Epoxidation of Allylic Alcohols Sharpless enantioselective epoxidation of allylic alcohols uses three components Enantioselectivity depends on the enantiomer of diethyl tartrate used 22 Sharpless Epoxidation of Allylic Alcohols Applied to the large scale synthesis of the gypsy moth sex pheromone and intermediates in cardiac drugs 23 Vicinal Halohydrins to Epoxides Vicinal halohydrins are converted to epoxides by base Mechanism 24 Vicinal Halohydrins to Epoxides Example Stereochemistry is conserved in the reaction sequence 25 Grignard Reagents and Epoxides Section 15 4 showed Grignard reactions opening epoxides to afford alcohols Other anionic nucleophiles react in a similar fashion 26 Alkoxide Nucleophiles and Epoxides In common with SN2 reactions there is inversion of stereochemistry And the least hindered carbon is attacked 27 Nucleophilic Reactions and Epoxides Grignard reagents are as selective as other anionic nucleophiles Reaction with lithium aluminum hydride is selective and yields and alcohol 28 Epoxide Ring Opening Mechanism Reaction equation Step 1 Nucleophilic Attack Step 2 Protonation 29 Acid Catalyzed Ring Opening Reaction equation Regioselectivity is reversed from what is observed in nucleophilic attack Nucleophile adds to most substituted carbon 30 Acid Catalyzed Ring Opening Transition state has the most stabilized carbocation 31 Ring Opening with Hydrogen Halides Primarily yields the trans product 32 Acid Catalyzed Ring Opening Mechanism Reaction equation Step 1 Protonation 33 Acid Catalyzed Ring Opening Mechanism Step 2 Nucleophilic attack Step 3 Deprotonation 34 Anti Hydroxylation of Alkenes Sequence of epoxidation followed by acid catalyzed ring opening gives an overall transformation of alkenes to anti diols 35 Epoxides in Biochemical Processes Monooxygenases effect epoxidation Reducing agent NADH is also required Example 36 Sulfides from Substitution Reactions SN2 reactions with primary and secondary halides Example 37 Oxidation of Sulfides Sulfoxides and Sulfones Sequential oxidation yields sulfoxides then sulfones Sodium metaperiodate yields sulfoxides Hydrogen peroxide yields sulfones 38 IR Spectroscopy Ethers have a strong band due to antisymmetric C O C stretching between 1070 and 1150 cm 1 39 IR Spectroscopy Epoxides typically have three bands 810 950 and 1250 cm 1 asymmetric and symmetric stretching of ring 750 840 cm 1 C S C stretching vibration gives weak signal around 600700 cm 1 Sulfoxides show a strong S O stretching at 1030 1070 cm 1 Sulfones show strong S O stretching bands at 1120 1160 cm 1 symmetric and 1290 1350 cm 1 asymmetric 40 NMR Spectroscopy The less electronegative sulfur has less effect on proton and carbon chemical shifts than oxygen 1 13 H NMR C NMR 41 Other Spectra UV Vis lmax for ethers is at 185 nm and are usually transparent above 220 nm Mass Spectrometry Ethers lose an alkyl radical from their molecular ion Gives an oxygen stabilized cation 42