18.7 Cyclic Ethers: Epoxides Cyclic ethers behave like acyclic ethers, except if ring is 3-membered Dioxane, tetrahydrofuran (THF) and furan are used as solvents 1,4-dioxane tetrahydrofuran (THF) furan Epoxides (oxiranes) are three- membered cyclic ethers. The strain of the three-member ring of epoxides gives them unique chemical reactivity. 1 Nomenclature of Epoxides The nonsystematic name, –ene oxide, describes the method of formation. The systematic name, epoxy, describes the location of the epoxide ring. (nonsystematic) (nonsystematic) (systematic) (systematic) 2 Name the following A. B. C. H3C CH3 H3C HC CH O 2 H3C C C CH3 O O 3 Preparation of Epoxides The simplest and commercially most important example is ethylene oxide, manufactured from ethylene, air, and a silver catalyst. In the laboratory, epoxides are most commonly prepared from alkenes and organic peroxy acids. The reaction occurs in one step with syn stereochemistry. alkene peroxy acid epoxide carboxylic acid 4 Epoxides from Halohydrins Addition of HO-X to an alkene gives a halohydrin Treatment of a halohydrin with base gives an epoxide 1. Cl , H O Intramolecular Williamson ether synthesis 2 2 2. NaOH, H2O 5 18.8 Ring-Opening Reactions of Epoxides Water adds to epoxides with dilute acid at room temperature. Because of ring strain, epoxides react under milder conditions. Product is a 1,2-diol (glycol). Mechanism: acid protonates oxygen and water adds to opposite side (anti addition, trans product) 6 Ethylene Glycol 1,2-ethanediol from acid catalyzed hydration of ethylene oxide EG is primarily used as a raw material in the manufacture of polyester fibers and fabric industry, and polyethylene terephthalate resins (PET) used in bottling. Widely used as automobile antifreeze (lowers freezing point of water solutions) 7 18.8 Ring-Opening Reactions of O HO OH Epoxides (FormationH+ of 1,2-alkoxyalcohol) C C + H OH C C Other nucleophiles (such as alcohols)glycol add similarly to epoxides. O HO OR H+ C C R OH C C 2-alkoxyalcohol O R OMgX R OH H2O OrganometallicC C + R MreagentgX C C C C H+ R R' R R' H+ HC CH + R'' ONa HC CH O HO OR'' 8 HO OH OO HO OH H++ + H CC CC + HH OOHH CC CC 18.8 Ring-Opening Reactionsgglylyccool l of Epoxides O HO OR O + HO OR HH+ CC CC RR OOHH CC CC The reactions with organometallic reagents (RMgX and RLi) are useful two-carbon chain22-a--allengtheningklkooxxyyaalclcoohhool l reactions. R OMgX R OH OO R OMgX R OH ether HH2OO C C + R MgX C C 2 C C C C + R MgX C C + C C HH+ Halohydrins from Epoxides Anhydrous HF, HBr, HCl, or HI combines with an epoxide, gives trans product Where X = F, Br, Cl, or I H HX O ether H 9 Regiochemistry of Acid-Catalyzed Opening of Epoxides (2o vs 1o, 3o vs 1o) When both epoxide carbons are 1 or 2, halogen attack occurs primarily at the less hindered site. Secondary Primary O HCl H3C C C H ether H H When one epoxide carbon is 3, halogen attack occurs at the more highly substituted site. The mechanism is midway between SN2 and SN1. The reaction occurs by backside attack (SN2), but a positive charge is stabilized by a tertiary carbocation-like transition state (SN1). Tertiary O Primary HCl H3C C C H ether H3C H 10 Complete the following reactions. H+ A. H2C CH2 H C CH + HO CH3 2 2 O OH OCH3 H C CH OH 3 3 + HC CH H H3C O B. + CH HC O HO CH3 H C 3 CH3 CH3 HC CH2 + H Br C. HC CH2 + HC CH2 O OH Br Br OH major minor 11 Complete the following reactions. H3C CH3 + H3C CH3 D. H HC CH CH CH + H3C ONa O HO OCH3 H C CH H C CH 3 3 H+ 3 3 E. HC CH CH CH + H5C2 ONa O HO OC2H5 H O+ H2C CH2 3 + H3C CH2 CH2 CH2 MgBr H3C CH2 CH2 CH2 CH2 CH2 OH O F. 12 18.9 Crown Ethers Large cyclic ethers were discovered in 1960. Central cavity is electronegative and attracts cations They are named in the general format: X-crown-Y ether X= total atoms in ring Y= number of oxygens O O O O O O O O O O O O O O O O O O O O O O 30-Crown-10 ether 24-Crown-8 ether 13-Crown-4 ether 13 Uses of Crown Ethers Complexes between crown ethers and ionic salts are soluble in nonpolar organic solvents Creates reagents that are free of water that have useful properties Inorganic salts dissolve in organic solvents leaving the anion unassociated, enhancing reactivity 14 Crown Ethers Crown ethers are able to solvate metal cations, different size crown ethers solvate different size cations. O O O O O O + O + O + Li Na K MnO4 O O O O O O O 15 12-Crown-4 ether 15-Crown-5 ether 18-Crown-6 ether 18.10 Spectroscopy of Ethers IR Spectroscopy: Ethers are difficult to identify since many other types of absorptions occur at the 1050 – 1150 cm-1 range where ethers absorb. NMR: 13C NMR ether carbons absorb in 50 – 80 range. 1H NMR hydrogens on carbons next to an ether oxygen absorb in 3.4 – 4.5 range. Hydrogens on carbons next to an epoxide oxygen absorb near 2.5 – 3.5 , and –OH in 3 –8 range. 16 18.11 Thiols and Sulfides Sulfur is the element just below oxygen in the periodic table, and many oxygen-containing organic compounds have sulfur analogs. Thiols, R-SH, are sulfur analogs of alcohol Sulfides, R-S-R’, are sulfur analogs of ethers. 17 Thiol Nomenclature Thiols are named in a similar way as alcohols, in terms of the numbering of carbons, keep the terminal -e and add the suffix –thiol. The –SH group itself is referred to as the mercapto group when it is a lower priority (“capturer of mercury”). ethanethiol cyclohexanethiol m-mercaptobenzoic acid 18 Mercaptans Gases like hydrogen sulfide H2S are mixed to give natural gases their pungent smell. Mercaptans were in the news with the Porter Ranch, CA leaks (2015-16). Human noses can easily detect sulfur compounds that belong to the Thiol class. Other compounds like ethanethiol and propanethiol are added to increase the amount of smell that these gasses give. These compounds are called warning agents, because they help warn you of a gas leak. Besides utility companies need for mercaptan, there are other trades that use it. Industries use it for jet fuel, pharmaceuticals and livestock feed additives. It is used in many chemical plants. Mercaptan is less corrosive and less toxic than similar sulfur compounds and found naturally in rotten eggs, onions, garlic, skunks, and, of course, bad breath. In other words, forms of mercaptan can be found in things that smell. 19 Properties of Thiols Thiols have low boiling points (because of reduced hydrogen bonding. Thiols have a strong, disagreeable odor. It is added to natural gas, and is responsible for the odors of skunks. Thiols are easily oxidized but yield different products than their alcohol analogs. (Thiols form disulfides) 20 Skunks The family of chemicals that a skunk sprays are (E)-2-butene-1-thiol, 3-methyl-1-butanethiol and thioacetates. They're volatile, which means they disperse easily in the air, and they're easily picked up by the human nose. (E)-2-butene-1-thiol 3-methylbutane-1-thiol thioacetate 21 http://www.compoundchem.com/wp-content/uploads/2014/04/The- 22 Chemistry-of-Body-Odours-2015.png Sulfide Nomenclature Sulfides (R-S-R), are sulfur analogs of ethers Named by rules used for ethers, with sulfide in place of ether for simple compounds and alkylthio in place of alkoxy dimethyl sulfide methyl phenyl sulfide 3-(methylthio)cyclohexene 23 Problems: Draw the structures for the following: 2-butanethiol 2,2,6-trimethyl-4-heptanethiol ethyl methyl sulfide 24 Thiols: Formation and Reaction Formation of alkyl thiols is done by SN2 nucleophilic displacement with sulfhydryl ion. Yields are often poor unless excess nucleophile is used. R-X + SH CH3CH2Br + NaSH Thiourea can be used to get a better yield, RCH2Br RCH2SH 25 Oxidation of Thiols to Disulfides Thiols are easily oxidized to disulfide compounds by a mild oxidizing agent such as hydrogen peroxide, iodine or bromine. This reaction is reversible using Zn and Acid. I2, H2O 2 RSH thiol Zn, H+ 26 Thiol to Thiolate to Sulfide Thiols react with aqueous base (NaOH or NaH) to give thiolates, RSH + NaOH which can react with a 1, or 2 alkyl halide to form a sulfide by SN2 mechanism. CH3CH2SNa + CH3CH2I 27 Sulfides as Nucleophiles Preparation of Sulfides R-S + R’CH2Br Sulfur compounds are more nucleophilic than oxygen analogs due to the valence electrons on the sulfur being farther from the nucleus and less tightly held. Sulfides react with primary alkyl halides (SN2) to give + trialkylsulfonium salts (R3S ) THF S H3C I H3C CH3 + 28 Oxidation of Sulfides Sulfides are easily oxidized with H2O2 to a sulfoxide (R2SO) Oxidation of a sulfoxide with a peroxyacid yields a sulfone (R2SO2) Dimethyl sulfoxide (DMSO) is often used as a polar aprotic solvent 29 Preview of Carbonyl Compounds Your textbook has a preview of carbonyl compounds between chapters 18 & 19 on Pages 743 – 752. Be sure to review and study these pages to help you better understand the material to come. 30 Chapter 19. Aldehydes and Ketones: Nucleophilic Addition Reactions 31 Aldehydes and Ketones Aldehydes and ketones are characterized by the the carbonyl functional group (C=O) aldehyde ketone The compounds occur widely in nature as intermediates in metabolism and biosynthesis Aldehydes and ketones are bonded to substituents that cannot stabilize a negative charge and therefore cannot act as leaving groups.