* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Ethers, Epoxides and Sulfides
George S. Hammond wikipedia , lookup
Aromaticity wikipedia , lookup
Enantioselective synthesis wikipedia , lookup
Homoaromaticity wikipedia , lookup
Bottromycin wikipedia , lookup
Kinetic resolution wikipedia , lookup
Hofmann–Löffler reaction wikipedia , lookup
1,3-Dipolar cycloaddition wikipedia , lookup
Organosulfur compounds wikipedia , lookup
Ring-closing metathesis wikipedia , lookup
Wolff rearrangement wikipedia , lookup
Stille reaction wikipedia , lookup
Discodermolide wikipedia , lookup
Asymmetric induction wikipedia , lookup
Hydroformylation wikipedia , lookup
Tiffeneau–Demjanov rearrangement wikipedia , lookup
Elias James Corey wikipedia , lookup
Nucleophilic acyl substitution wikipedia , lookup
KOT 222 Organic Chemistry II CHAPTER 14 ETHERS, EPOXIDES, and SULFIDES 1 Ethers ¾ Formula: R-O-R’, where R and R’ maybe alkyl or aryl groups. Symmetrical ethers: CH3 Unsymmetrical ethers: O CH3 O CH3 O 2 Structure and Polarity sp3 hybridized Bulky alkyl groups enlarge the angle 3 Boiling Points ¾ Large dipole moments resulting in dipole-dipole interactions. ¾ Similar to alkanes of comparable MW. ¾ Much lower than alcohols of comparable MW. 4 Hydrogen Bond Acceptor ¾ Ether cannot form hydrogen bond with another ether molecule. ¾ Its lone pair electron can form a hydrogen bond with hydrogen bond donor with O-H or N-H. 5 Ethers as Solvents ¾ Nonpolar substances are more soluble in ethers than in alcohols. ¾ Ether has large dipole moment, so polar solutes also dissolve. ¾ Ethers solvate cations but not small anions. ¾ Ethers are nonhydroxylic, so they do not react with strong bases. 6 Ether Complexes Grignard reagents: Ethers share their lone pairs of electrons with the magnesium, stabilize the reagent and keep it in the solution. Electrophiles, BH3: Ether’s nonbonding electrons stabilize BH3. Metal cations: Crown ethers solvate metal cations by complexing the metal in the center of the ring. Allowing polar inorganic salts to dissolve in nonpolar organic solvents. H _ + O B H H BH3 THF 7 Nomenclature of Ethers a) Common names a) Alkyl alkyl ether b) Current rule: alphabetical order c) Old rule: order of increasing complexity d) Symmetrical: use dialkyl, or just alkyl. CH3 CH3CH2 O CH2CH3 diethyl ether or ethyl ether CH3 O C CH3 CH3 t-butyl methyl ether or methyl t-butyl ether 8 b) IUPAC names b) Alkoxy alkane c) Complex alkyl group as the root name, the rest is the alkoxy group. CH3 CH3 O C O CH3 CH3 CH3 2-methyl-2-methoxypropane Methoxycyclohexane 9 c) Cyclic ethers ¾ Heterocyclic compounds, O is the heteroatom. Epoxides (Oxiranes): ¾ three-membered cyclic ethers. H H peroxybenzoic acid O H cyclohexene H cyclohexene oxide H 5 4 CH3 H 6 3 1 2 1 O O H trans-1,2-epoxy-4methylcyclohexane H H3CO CH3 2 3 H trans-2-methoxy-3-methyloxirane 10 Oxetanes: 1 O 4 ¾ four-membered cyclic ethers. O H3 C 3 CH2CH3 2 H 3C H 2-ethyl-3,3-dimethyloxetane Furans (Oxolanes): ¾ five-membered cyclic ethers. O O tetrahydrofuran, THF Pyrans (Oxanes): O ¾ six-membered cyclic ethers. O tetrahydropyran, THP 11 Dioxanes: ¾ six-membered cyclic ethers with two oxygen atoms. ¾ the most common is 1,4-dioxane. ¾1,4-dioxane fused with two benzene rings to give a dioxin. O O O O 1,4-dioxane dibenzo-1,4-dioxane, dioxin 12 Spectroscopy of Ethers ¾ Infrared spectroscopy moderate to strong C-O stretching around 1000 to 1200 cm-1. lack of C=O and O-H absorption bands suggests an ether. ¾ NMR spectroscopy H C H C δ65 - δ90 13 O H δ3.5 - δ4 1 13 ¾ Mass spectrometry Common fragmentations are: 14 Mass spectrum of diethyl ether 15 Williamson Ether Synthesis ¾ Most reliable and versatile ether synthesis. ¾ SN2 attack of alkoxide ion on 1o alkyl halide or tosylate. CH3 CH3 O H + K CH3 CH3 CH3 CH3 _ O + CH3CH2 CH3 CH3 _ + O K CH3 H C H CH3 Br CH3 _ O CH2CH2CH3 + Br CH3 16 Alkoxymercuration-Demercuration ¾ Use mercuric acetate with an alcohol to add RO-H to a double bond and form the Markovnikov product. 17 Bimolecular Dehydration of Alcohols ¾ Industrial method, not good lab synthesis. ¾ The alcohol must have 1o alkyl group. CH3CH2 O H + H O CH2CH3 H2SO4 CH3CH2 O CH2CH3 140°C ¾ Bulky alkyl group and high temperature lead to the formation of alkene (unidehydration). H2SO4 CH3 CH CH3 OH H 2C CH CH3 + H 2O 180oC 18 Cleavage of Ethers ¾ Ethers are unreactive toward base, but protonated ethers can undergo substitution reactions with strong acids. ¾ Alcohol leaving group is replaced by a halide. ¾ Reactivity: HI > HBr >> HCl R-O-R’ excess HX R-X + R’-X SN2 substitution mechanism 19 Mechanism for cleavage Step 1: Protonation of ether Step 2: SN2 cleavage of the protonated ether Step 3: Conversion of alcohol to alkyl halide CH3OH + HBr CH3Br + H2O SN1: 2o & 3oalcohols SN2: 1o alcohol 20 Phenyl Ether Cleavage ¾ Give alkyl halides and phenols as products. ¾ Phenol cannot react further to become halide. OH O CH2CH3 HBr + CH3CH2 Br 21 Autoxidation of Ethers ¾ A spontaneous oxidation by atmospheric oxygen. ¾ Ether is slowly oxidexed to hydroperoxide and dialkyl peroxide. ¾ Highly explosive!!! 22 Sulfides (Thioethers) ¾ Analogues of ethers, R-S-R’. ¾ Named like ethers: Common names – “sulfide” replacing “ether” IUPAC names – “alkylthio” replacing “alkoxy” S CH3 methyl phenyl sulfide or methylthiobenzene 23 Synthesis of Sulfides ¾ Easily synthesized by Williamson ether synthesis. ¾ Thiolate ion as the nucleophile. ¾ Sulfur is larger and more polarized than oxygen. ¾ Thiolates are better nucleophiles, weaker bases, than alkoxides. Br C H3 C _ C H3 H 2° halide C H 3S C H 3O H SC H3 C H3 C C H3 H Substitution product 24 Sulfide Reactions ¾ Sulfides are easily oxidized to sulfoxides and sulfones. sulfoxide sulfone ¾ Sulfides are often used as mild reducing agents. 25 ¾ Sulfides are relatively strong nucleophiles. - sulfur is large and more polarizable, its valence electrons are less tightly held. ¾ Sulfides attack unhindered alkyl halides to give sulfonium salts. ¾ Sulfonium salts are good alkylating agents. CH3 N + CH3 S CH3 N CH3 + CH3 S CH3 26 Synthesis of Epoxides ¾ Epoxide is a three-membered cyclic ether. ¾ Also called as oxirane. ¾ Can be synthesized from: 1. Peroxyacid epoxidation 2. Base-promoted cyclization of halohydrins 27 Peroxyacid Epoxidation ¾ Converts alkenes to epoxides (oxidation). ¾ Weakly acidic peroxyacid that is soluble in aprotic solvents is used. ¾ A one-step, concerted reaction. ¾ Epoxide retains the stereochemistry of the alkene used. 28 Cyclization of Halohydrins ¾ A variation of the Williamson ether synthesis. ¾ Treatment of a halohydrin with a base leads to an epoxide through internal SN2 attack. ¾ Halohydrins are synthesized by treating alkenes with aqueous solutions of halogens (X2/H2O). 29 Formation of halohydrin ¾ By treating alkenes with aqueous solution of halogens. ¾ Bromine water and chlorine water add across double bonds with Markovnikov orientation. Cyclization to give epoxide 30 Reactions of Epoxides ¾ Large ring strain energy causes epoxides more reactive than ethers. ¾ Epoxides react both under acidic and basic conditions which cause the opening of the ring. ¾ The products depend primarily on the solvent used. 31 Acid-catalyzed Ring Opening In Water ¾ Epoxides are hydrolyzed to give glycols (trans diols) with anti stereochemistry. SN2 32 Direct anti hydroxylation of alkene: 33 In Alcohols ¾ Produces an alkoxy alcohol with anti stereochemistry. 34 Using Hydrohalic Acids ¾ Produce a 1,2-dihalide. ¾ The reaction is analogous to the cleavage of ethers by HBr or HI. 35 Biosynthesis of Steroids ¾ Involved an acid-catalyzed opening of squalene2,3-epoxide. 36 The process repeats and leads to… 37 Base-Catalyzed Ring Opening ¾ Strong bases and nucleophiles do not cleave ethers as alkoxide ion is a poor leaving group. ¾ Epoxide’s high ring strain makes it susceptible to nucleophilic attack. 38 Mechanism: 39 ¾With aqueous hydroxide, a trans 1,2-diol is formed. ¾With alkoxide in alcohol, a trans 1,2-alkoxy alcohol is formed. ¾These are the same products that were formed in acid. ¾Different products are formed in acid and base if epoxide is unsymmetrical. 40 Amine can also open epoxides. Use excess ammonia to get good yields of ethanolamine. 41 Orientation of Epoxide Opening ¾ Unsymmetrically substituted epoxides give different products under acid-catalyzed and base-catalyzed conditions. 42 Under basic conditions: Base attacks the least hindered carbon in an SN2 displacement _ O O HC CH2 CH3 HC OCH2CH3 CH3CH2OH CH2 CH3 OCH2CH3 OH HC CH2 CH3 OCH2CH3 Under acidic conditions: The nucleophile attacks the protonated epoxide at the most substituted carbon. H O+ HC CH3CH2OH CH2 CH3 OH H3C HC CH2 2CH3 H OCH + OH H3C HC CH2 OCH2CH3 43 In protonated epoxide, sharing of the positive charge can be represented as below: The nucleophile attack the more substituted carbon, which can better support the positive charge and more electrophilic. 44 Reactions with Grignard and Organolithium Reagents • Strong base opens the epoxide ring by attacking the less hindered carbon. OH MgBr O H2C CHCH3 1) ether + 2) H3O CH2 CHCH3 + 45 46