Alcohols, Ethers and Thiel - Elementary Organic Chemistry | CHM 231, Study notes of Organic Chemistry

Download Alcohols, Ethers and Thiel - Elementary Organic Chemistry | CHM 231 and more Study notes Organic Chemistry in PDF only on Docsity! 8-1© 2005 John Wiley & Sons, IncAll rights reserved Chapter 8: Alcohols, Ethers, and Thiols 8-2© 2005 John Wiley & Sons, IncAll rights reserved Alcohols - Structure • Alcohols: The functional group of an alcohol is an -OH group bonded to an sp3 hybridized carbon • If the –OH group is bonded to an sp2 hybridized carbon, the molecules are called phenols or enols • Oxygen is also sp3 hybridized • two sp3 hybrid orbitals form sigma bonds to carbon and hydrogen • the remaining two sp3 hybrid orbitals each contain an unshared pair of electrons alcohol phenol enol 8-5© 2005 John Wiley & Sons, IncAll rights reserved Alcohols - Nomenclature • Examples: Ethanol (Ethyl alcohol) 1-Propanol (Propyl alcohol) 2-Propanol (Isopropyl alcohol) 1-Butanol (Butyl alcohol) OH OH OH OH 2-Butanol (sec-Butyl alcohol) 2-Methyl-1-propanol (Isobutyl alcohol) 2-Methyl-2-propanol (t ert-Butyl alcohol) OH Cyclohexanol (Cyclohexyl alcohol) OH OH OH 8-6© 2005 John Wiley & Sons, IncAll rights reserved Alcohols - Classification • We classify alcohols as primary (1), secondary (2), or tertiary (3), depending on whether the OH group is on a primary secondary or tertiary carbon 8-7© 2005 John Wiley & Sons, IncAll rights reserved Alcohols - Nomenclature • Compounds containing • two -OH groups are named as diols, • three -OH groups are named as triols, etc. CH3 CHCH2 HO OH CH2 CH2 OHOH CH2CHCH2 OHHOHO 1,2-Ethanediol (Ethylene glycol) 1,2-Propanediol (Propylene glycol) 1,2,3-Propanetriol (Glycerol, Glycerin) 8-10© 2005 John Wiley & Sons, IncAll rights reserved Intermolecular Forces (Van-der Waals forces) • London Forces (Dispersion Forces) • The only intermolecular forces in nonpolar molecules • Alkanes, Alkenes, Alkynes • Weak, increase with the number of electrons in the molecule • Dipole-Dipole interactions • Polar molecules (permanent Dipole) • Haloalkanes • Stronger than London Forces • Hydrogen bonding • The strongest intermolecular forces between neutral molecules • positive charge on hydrogen and a partial negative charge on a nearby oxygen or nitrogen (typically OH- or NH- groups) • Alcohols, amines, aminoacids, carboxylic acids • the strength of hydrogen bonding in alcohols is approximately 10 to 40 kJ/mol (C-C bond: 350 kJ/mol) 8-11© 2005 John Wiley & Sons, IncAll rights reserved Hydrogen Bonding • Hydrogen bonding: the attractive force between a partial positive charge on a hydrogen and a partial negative charge on a nearby oxygen or nitrogen atom • Figure 8.3 shows the association of ethanol molecules in the liquid state • Alcohols have high boiling points compared to hydrocarbons • Hydrogen bonds between different alcohol molecules • Alcohols have high solubilities in water compared to hydrocarbons • Hydrogen bonds between alcohol molecule and H2O molecules 8-12© 2005 John Wiley & Sons, IncAll rights reserved Solubilities • Hydrophilic • “water loving” • from Greek: “hydros”=water, “philia”=love, friendship • Molecules that are soluble in water • Polar molecules (alcohols, acids), hydrogen bonds • Hydrophobic=lipophilic • “water fearing” • From Greek: “hydros”=water, “phobos”=fear • Insoluble in water, soluble in nonpolar solvents • Apolar molecules (Alkanes, Alkenes, Alkynes), only London forces • Amphiphilic • From Greek “amphis”=both, “philia”=love, friendship • Polar and apolar parts in the molecule • Long hydrophobic chains with polar groups at the end of the chain • Fatty acids 8-15© 2005 John Wiley & Sons, IncAll rights reserved Acidity of Alcohols • Most alcohols are about the same or slightly weaker acids than water • aqueous solutions of alcohols have the same pH as that of pure water CH3 O H O H H [CH3 O - ][ H3O +] [ CH3OH] CH3 O H O H H + Ka = + + = 3.2 x 10-16 pKa = 15.5 8-16© 2005 John Wiley & Sons, IncAll rights reserved Acidity of Alcohols • pKa values for several low-molecular-weight alcohols (CH3 )3COH (CH3 )2CHOH CH3 CH2OH H2O CH3 OH CH3 COOH HCl Compound pKa -7 15.5 15.7 15.9 17 18 4.8 hydrogen chloride acetic acid methanol water ethanol 2-propanol 2-methyl-2-propanol Structural Formula Stronger acid Weaker acid *Also given for comparison are pKa values for water, acetic acid, and hydrogen chloride. 8-17© 2005 John Wiley & Sons, IncAll rights reserved Basicity of Alcohols • In the presence of strong acids, the oxygen atom of an alcohol behaves as a weak base • proton transfer from the strong acid forms an oxonium ion • thus, alcohols can function as both weak acids and weak bases • Just like water, alcohols are amphoteric CH3 CH2 -O-H H O H H H2SO4 CH3 CH2 -O H H H O H Ethyloxonium ion (pKa -2.4) • • Hydronium ion (pKa -1.7) Ethanol + + + + 8-20© 2005 John Wiley & Sons, IncAll rights reserved Reaction of a 3° ROH with HX • 3° Alcohols react with HX by an SN1 mechanism • Step 1: a rapid, reversible acid-base reaction transfers a proton to the OH group • this proton-transfer converts the leaving group from the strong base OH- (the conjugated base of the weak acid H2O and a poor leaving group), to the weak base H2O (the conjugated base of the strong acid H3O+) a better leaving group 8-21© 2005 John Wiley & Sons, IncAll rights reserved Reaction of a 3° ROH with HX • Step 2: loss of H2O from the oxonium ion gives a 3° carbocation intermediate • Step 3: reaction with halide ion completes the reaction CH3-C CH3 CH3 O H H CH3 -C + CH3 CH3 O H H slow, rate determining An oxonium ion + + A 3° carbocation intermediate SN 1 CH3-C + CH3 CH3 Cl CH3-C Cl CH3 CH3 fast + 2-Chloro-2-methylpropane (t ert -Butyl chloride) The energy diagram of the reaction is akin to SN1 reactions of Haloalkanes 8-22© 2005 John Wiley & Sons, IncAll rights reserved Reaction of a 1° ROH with HX • 1° alcohols react by an SN2 mechanism • Step 1: proton transfer to OH converts the leaving group from OH-, a poor leaving group, to H2O a better leaving group • Step 2: nucleophilic displacement of H2O by Br- Br - O H H slow, rate determining + + SN2 O H H Br The energy diagram of the reaction is akin to SN2 reactions of Haloalkanes 8-25© 2005 John Wiley & Sons, IncAll rights reserved Reaction with Thionylcholoride • Thionyl chloride, SOCl2, is the most widely used reagent for conversion of alcohols to alkyl chlorides SCl Cl O .. .. .. ..: : :: .. - .. .. :Cl: S Cl O H CH3 O C .. : : :.. .... : O S O .. .. .... :Cl: - .. .. inversion SN2 SN2 MECHANISM INVERSION .. : H CH3 O C H (S) C Cl CH3 H .. ::(R) “fragmentation” H+ H+ 8-26© 2005 John Wiley & Sons, IncAll rights reserved Reaction with Thionylcholoride The Artifical Sweetner Splenda (Sucralose) O O O OH HO OHHO HO HO OH OH SOCl2 O O O Cl HO OHCl HO HO Cl OH Splenda (Sucralose) (Blocking and Deblocking Steps Required) 8-27© 2005 John Wiley & Sons, IncAll rights reserved Dehydration of Alcohols • As with Haloalkanes, eliminations are often competing with nucleophilic substitutions • An alcohol can be converted to an alkene by elimination of H and OH from adjacent carbons (a -elimination) • 1° alcohols must be heated at high temperature in the presence of an acid catalyst, such as H2SO4 or H3PO4 • 2° alcohols undergo dehydration at somewhat lower temperatures • 3° alcohols often require temperatures only at or slightly above room temperature 8-30© 2005 John Wiley & Sons, IncAll rights reserved Dehydration of Alcohols • When isomeric alkenes are obtained, the more stable alkene (the one with the greater number of substituents on the double bond) generally predominates (Zaitsev’s rule) CH3CH2CHCH3 OH 85% H3PO4 CH3CH=CHCH3 CH3CH2 CH=CH2 1-Butene (20%) 2-Butene (80%) 2-Butanol + heat 8-31© 2005 John Wiley & Sons, IncAll rights reserved Dehydration of a 2° Alcohol • A three-step mechanism • Step 1: proton transfer from H3O+ to the -OH group converts OH-, a poor leaving group, into H2O, a better leaving group CH3CHCH2CH3 HO O H H H O H H CH3CHCH2CH3 O H H+ An oxonium ion rapid and reversib le + + + 8-32© 2005 John Wiley & Sons, IncAll rights reserved Dehydration of a 2° Alcohol • Step 2: loss of H2O gives a carbocation intermediate • Step 3: proton transfer from an adjacent carbon to H2O gives the alkene and regenerates the acid catalyst H O H CH3CHCH2 CH3 CH3CHCH2CH3 H2O + s low, rate determining + + A 2° carbocation intermediate CH3 -CH-CH-CH3 H O H H CH3 -CH=CH-CH3 O H HH rapid+ + + + 8-35© 2005 John Wiley & Sons, IncAll rights reserved Oxidation of Alcohols • Primary alcohols can be oxidized to aldehydes or carboxylic acids, depending on the oxidizing agent and experimental conditions • Seondary alcohols can be oxidized to ketones aldehyde carboxylic acid ketone no oxidation without breaking C-C bonds 8-36© 2005 John Wiley & Sons, IncAll rights reserved Oxidation of Alcohols • the most common oxidizing agent is chromic acid • chromic acid oxidation of 1-octanol gives octanoic acid CrO3 H2O H2SO4 H2CrO4+ Chromic acidChromium(VI) oxide CH3(CH2)6CH2OH CrO3 H2SO4 , H2O CH3(CH2)6CH O CH3(CH2)6COH O Octanal (not isolated) Octanoic acid1-Octanol 8-37© 2005 John Wiley & Sons, IncAll rights reserved Oxidation of Alcohols • to oxidize a 1° alcohol to an aldehyde, use PCC • PCC selectively oxidizes 1 alcohols to aldehydes • PCC does not oxidize C=C double bonds • PCC oxidation of geraniol gives geranial CrO3 HCl N N H CrO3Cl - Pyridinium chlorochromate (PCC) Pyridine + + + OH PCC CH2 Cl2 H O Geraniol Geranial 8-40© 2005 John Wiley & Sons, IncAll rights reserved Ethers - Physical Properties • Ethers are polar molecules • each C-O bond is polar covalent • however, only weak attractive forces exist between ether molecules • Dipole-dipole interactions in pure ethers (no H2O) 8-41© 2005 John Wiley & Sons, IncAll rights reserved Ethers - Physical Properties • In solutions with water, ethers are hydrogen bond donors • Which explains solubility of ethers with small alkane chains in water 8-42© 2005 John Wiley & Sons, IncAll rights reserved Ethers - Physical Properties • Comparison of ethers to alcohols and alkanes alcohol hydrogen bonds soluble in water in any proportion ether dipole interactions solubility in water: 8g/100g alkane London forces insoluble in water 8-45© 2005 John Wiley & Sons, IncAll rights reserved Reactions of Ethers • Ethers resemble hydrocarbons in their resistance to chemical reaction • they do not react with strong oxidizing agents such as chromic acid, H2CrO4 • they are not affected by most acids and bases at moderate temperatures • Because of their good solvent properties and general inertness to chemical reaction, ethers are excellent solvents in which to carry out organic reactions 8-46© 2005 John Wiley & Sons, IncAll rights reserved Cyclic Ethers • Although cyclic ethers have IUPAC names, their common names are more widely used • IUPAC: • the prefix ox- shows that the ring contains an oxygen atom • he suffixes –irane, -etane, -olane, and –ane indicate three, four, five and six atoms in a saturated ring (an epoxide) 8-47© 2005 John Wiley & Sons, IncAll rights reserved Cyclic Ethers • Prepared by internal nucleophilic substitution • Similar chemical properties as non-cyclic ethers • Exception: three and four membered rings 8-50© 2005 John Wiley & Sons, IncAll rights reserved Reactions of Epoxides • ethers are generally unreactive to aqueous acid • epoxides, however, react readily because of the angle strain in the three-membered ring • reaction of an epoxide with aqueous acid gives a glycol • Antifreeze and a starting material for polyethylene terephtalate (PET) plastics CH2 CH2 O H2 O H+ HOCH2 CH2OH+ 1,2-Ethanediol (Ethylene glycol) Ethylene oxide 8-51© 2005 John Wiley & Sons, IncAll rights reserved Reactions of Epoxides • Ring opening reaction follows the SN2 mechanism • Anti-orientation + H2 O H+ 1,2-Epoxycyclopentane (Cyclopentene oxide) trans-1,2-Cyclopentanediol OH OH O H H What is the mechanism of this reaction? 8-52© 2005 John Wiley & Sons, IncAll rights reserved A Cycloalkene to a Glycol • both cis and trans glycols can be prepared RCO3 H OsO4 , t-BuOOH O H H H + OH OH H2O OH OH t rans-1,2-Cyclopentanediol cis -1,2-Cyclopentanediol 8-55© 2005 John Wiley & Sons, IncAll rights reserved Epoxides as Anti-Cancer Drugs • Epothilone B • Reacts with Tubulin proteins • Stops cells from dividing properly 8-56© 2005 John Wiley & Sons, IncAll rights reserved Thiols - Structure • The functional group of a thiol is an -SH (sulfhydryl) group bonded to an sp3 hybridized carbon • analogs of alcohols 8-57© 2005 John Wiley & Sons, IncAll rights reserved Thiols - Nomenclature • IUPAC names: • the parent chain is the longest chain containing the -SH group • add -thiol to the name of the parent chain • Common names: • name the alkyl group bonded to sulfur followed by the word mercaptan • alternatively, indicate the -SH by the prefix mercapto Ethanethiol (Ethyl mercaptan) 2-Methyl-1-propanethiol (Isobutyl mercaptan) 2-Mercaptoethanol SH SH HS OH 8-60© 2005 John Wiley & Sons, IncAll rights reserved Acidity of Thiols • Thiols are stronger acids than alcohols • Why is this the case? • Thiols react with strong bases to form salts CH3CH2SH CH3CH2OH H2 O H2 O CH3CH2S - CH3CH2O - H3 O + H3 O + pKa = 8.5 pKa = 15.9 + ++ + CH3CH2SH Na + OH - CH3CH2S - Na + H2O+ + Stronger acid Stronger base Weaker base Weaker acid pKa 8.5 pKa 15.7 8-61© 2005 John Wiley & Sons, IncAll rights reserved Oxidation of Thiols • thiols are oxidized by a variety of oxidizing agents, including O2, to disulfides • disulfides, in turn, are easily reduced to thiols by several reagents • this easy interconversion between thiols and disulfides is very important in protein chemistry 2HOCH2 CH2 SH HOCH2 CH2S-SCH2 CH2 OH A disulfide oxidation reduction A thiol 8-62© 2005 John Wiley & Sons, IncAll rights reserved Oxidation of Thiols • The aminoacids Cystein and Methionin contain sulfur • Disulfide bridges are important in stabilizing the tertiary structure in proteins Cystein Methionin location of disulfide bridges in antibodys