Organic Chemistry I Mohammad Jafarzadeh Faculty of Chemistry, Razi University Organic Chemistry, Structure and Function (7th edition) By P. Vollhardt and N. Schore, Elsevier, 2014 1 336 CHAPTER 9 Further Reactions of Alcohols and the Chemistry of Ethers In Summary Another mode of reactivity of carbocations, in addition to regular SN1 and E1 processes, is rearrangement by hydride or alkyl shifts. In such rearrangements, the migrating group delivers its bonding electron pair to a positively charged carbon neighbor, exchanging places with the charge. Rearrangement may lead to a more stable cation—as in the conversion of a secondary cation into a tertiary one. Primary alcohols also can 336 CHAPTER undergo9 Further rearrangement, Reactions but ofthey Alcohols do so by andconcerted the Chemistry pathways and of notEthers through the inter- mediacy of primary cations. In Summary Another mode of reactivity of carbocations, in addition to regular SN1 and E1 processes, is rearrangement by hydride or alkyl shifts. In such rearrangements, the 9-4migrating ESTERS group deliversFROM its ALCOHOLS bonding electron AND pair to HALOALKANE a positively charged SYNTHESIS carbon neighbor, exchanging places with the charge. Rearrangement may lead to a more stable cation—as Reactionin the of conversionalcohols with of a carboxylicsecondary cationacids convertsinto a tertiary them one.to organic Primary esters,alcohols also also called can carboxylatesundergo rearrangement,or alkanoates but (Table they 2-3).do so Theyby concerted are formally pathways derived and not from through the carboxylicthe inter- acids mediacyby replacement of primary of thecations. hydroxy group with alkoxy. One can formulate a corresponding set of inorganic esters derived from inorganic acids, such as those based on phosphorus and sulfur in various oxidation states. In such inorganic esters, the attachment of the 9-4 ESTERS FROMOrganic ALCOHOLS and Inorganic AND EstersHALOALKANE SYNTHESIS ReactionO of alcohols withO carboxylic HOacids converts them toO organic esters,O also called carboxylatesB or alkanoatesB (Table 2-3). GThey are formally derivedB from the Mcarboxylic 9.4 ESTERS FROMacidsC byALCOHOLS replacementHO OOofAND Pthe hydroxyOHHALOALKANE group withPO OHalkoxy.SYNTHESIS OneROO canS formulateOH a correspondingSOOH R OH A D B D set of inorganic esters OHderived from inorganicHO acids, such asO those based onHO phosphorus Reaction of alcoholsA carboxylicand sulfur withacid in carboxylicvariousPhosphoric oxidation acidacids states. Phosphorousconverts In such acid theminorganicto A sulfonic esters,organic acid the attachmentesters,Sulfurousalso of acid thecalled carboxylates or alkanoates. (An organic acid) Organic and Inorganic(Inorganic Esters acids) O O O O HO HO O O OO B B B B G G B B MM C C OOPHO OROHOOOЈ P OH POOROPOЈ OH OOSR ROOORSOOHЈ SSOOOROHO Ј R ORЈ R OHA A D D B B DD OH OH HO HO O O HOHO A carboxylic acid Phosphoric acid Phosphorous acid A sulfonic acid Sulfurous acid A carboxylate ester(An organic A phosphate acid) ester A phosphite ester(Inorganic A sulfonate acids) ester A sulfite ester (An organic ester) (Inorganic esters) O O HO O O heteroatomB turns the normallyB poor leavingG group OH in alcoholsB into a good leavingM group C OOPHO ORO Ј POORO Ј OOSR ORO Ј SOORO Ј R(highlightedORЈ in the greenA boxes), which Dcan be used in the Bsynthesis of haloalkanesD (see also Section 9-2). We haveOH already mentionedHO the good leaving-groupO abilityHO of sulfate and A carboxylatesulfonate ester groups Ain phosphate SN2 reactions ester (Section A phosphite 6-7). ester Here, we A sulfonateshall see ester how speci A! sulfite c phosphorus ester (Anand organic sulfur ester) reagents accomplish this task: (Inorganic esters) ϩ heteroatom turns the normallyReagent poor leaving group OHX inϪ alcohols into a good leaving group (highlighted in ROHtheO green boxes), whichR canO Lbe used in the synthesisROX of haloalkanes (see Alcohol Inorganic Haloalkane also Section 9-2). We have already mentioned the good leaving-group ability of sulfate and 2 ester sulfonate groups in SN2 reactions (Section 6-7). Here, we shall see how speci! c phosphorus and sulfur reagents accomplish this task: Alcohols react with carboxylicϩ acids to give organic esters Reagent XϪ Alcohols react with carboxylicROHO acids in theR OpresenceL of catalyticRO Xamounts of a strong Alcohol Inorganic Haloalkane inorganic acid, such as H2SO4 or HCl, to give organic esters and water, a process called ester esteri! cation. Starting materials and products in this transformation form an equilibrium that can be shifted in either direction. The formation and reactions of organic esters will be presentedAlcohols in detail react in Chapters with carboxylic19 and 20. acids to give organic esters Alcohols react with carboxylic acids in the presence of catalytic amounts of a strong Esterification inorganic acid, such as H2SO4 or HCl, to give organic esters and water, a process called esteri! cation.O Starting materials and products in thisO transformation form an equilibrium that can be Bshifted in either direction. The Hformationϩ andB reactions of organic esters will be presented 3inCOHCH detail ϩϩin ChaptersCH3CH 1922OH and 20. CH3COCH CH3 HOH Acetic acid Ethanol Ethyl acetate solvent Esterification O O B Hϩ B 3COHCH ϩϩCH3CH22OH CH3COCH CH3 HOH Acetic acid Ethanol Ethyl acetate solvent 336 CHAPTER 9 Further Reactions of Alcohols and the Chemistry of Ethers In Summary Another mode of reactivity of carbocations, in addition to regular SN1 and E1 processes, is rearrangement by hydride or alkyl shifts. In such rearrangements, the migrating group delivers its bonding electron pair to a positively charged carbon neighbor, exchanging places with the charge. Rearrangement may lead to a more stable cation—as in the conversion of a secondary cation into a tertiary one. Primary alcohols also can undergo rearrangement, but they do so by concerted pathways and not through the inter- mediacy of primary cations. 9-4 ESTERS FROM ALCOHOLS AND HALOALKANE SYNTHESIS Reaction of alcohols with carboxylic acids converts them to organic esters, also called carboxylates or alkanoates (Table 2-3). They are formally derived from the carboxylic acids by replacement of the hydroxy group with alkoxy. One can formulate a corresponding set of inorganic esters derived from inorganic acids, such as those based on phosphorus and sulfur in various oxidation states. In such inorganic esters, the attachment of the Organic and Inorganic Esters O O HO O O B B G B M C HOOOP OH POOH ROOS OH SOOH R OH A D B D OH HO O HO A carboxylic acid Phosphoric acid Phosphorous acid A sulfonic acid Sulfurous acid (An organic acid) (Inorganic acids) O O HO O O B B G B M C OOPHO ORO Ј POORO Ј OOSR ORO Ј SOORO Ј R ORЈ A D B D OH HO O HO A carboxylate ester A phosphate ester A phosphite ester A sulfonate ester A sulfite ester (An organic ester) (Inorganic esters) heteroatom turns the normally poor leaving group OH in alcohols into a good leaving group (highlighted in the green boxes), which can be used in the synthesis of haloalkanes (see also Section 9-2). We have already mentioned the good leaving-group ability of sulfate and sulfonate groups in SN2 reactions (Section 6-7). Here, we shall see how speci! c phosphorus and sulfur reagents accomplish this task: ϩ Reagent XϪ ROHO ROL ROX Alcohol Inorganic Haloalkane ester Alcohols react with carboxylic acids to give organic esters Alcohols react with carboxylic acids in the presence of catalytic amounts of a strong inorganic acid, such as H2SO4 or HCl, to give organic esters and water, a process called esteri! cation. Starting materials and products in this transformation form an equilibrium Alcohols react with carboxylicthatacids can be inshiftedthe in presenceeither direction.of Thecatalytic formationamounts and reactionsof of aorganicstrong esters will be presented in detail in Chapters 19 and 20. inorganic acid, such as H2SO4 or HCl, to give organic esters and water, a process called esterification (an equilibrium). 9-4 Esters from Alcohols andEsterification Haloalkane Synthesis CHAPTER 9 337 O O B Hϩ B 3COHCH ϩϩCH3CH22OH CH3COCH CH3 HOH Haloalkanes can be madeAcetic from acid alcoholsEthanol through Ethyl acetate inorganic esters solvent Haloalkanes canBecausebe ofmade the dif! cultiesfrom andalcohols complicationsthrough that can inorganicbe encounteredesters in the acid-catalyzed conversions of alcohols into haloalkanes (Section 9-2), several alternatives have been devel- Although written as H3PO3, oped. These methods rely on a number of inorganic reagents that are capable of changing phosphorous acid is a These methodsthe hydroxyrely on functiona number into a goodof inorganicleaving group reagentsunder milder thatconditions.are capableThus, primaryof andchanging mixturethe of two tautomers: hydroxy functionsecondaryinto aalcoholsgood reactleaving with phosphorusgroup under tribromide,milder a readilyconditions available .commercial com- O OH B A pound, to give bromoalkanes and phosphorous acid. This method constitutes a general way C PH PHE H ( OH HO OH Primary and secondaryof making bromoalkanesalcohols fromreact alcohols.with All phosphorusthree bromine atomstribromide are transferredto fromgive phos-bromoalkanesHO and phosphorousphorusacid to alkyl. All groups.three bromine atoms are transferred to alkyl groups. Major Minor Phosphorous acid Bromoalkane Synthesis by Using PBr3 (CH3CH2)2O 3 A ϩ PBr3 3 A ϩ H3PO3 OH Br ReactionR 47% 3-Pentanol Phosphorus 3-Bromopentane Phosphorous 3 tribromide acid What is the mechanism of action of PBr3? In the ! rst step, the alcohol attacks the phosphorus reagent as a nucleophile to form a protonated inorganic ester, a derivative of phosphorous acid. Mechanism Step 1 Br PBr ϩ 2 i i Ϫ RCH2š"OH ϩϩðP OOBr"šð RCH2 Oš ðBr"šð f f Br H Next, HOPBr2, a good leaving group, is displaced (SN2) by the bromide generated in step 1, producing the haloalkane. Step 2 PBr ϩ 2 Ϫ f ðBr"šð ϩ RCH2 OšO RCH2 Br"šð ϩ HOPBr"š 2 i H This method of haloalkane synthesis is especially ef! cient because HOPBr2 continues to react successively with two more molecules of alcohol, converting them into haloalkane as well.