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Química Organica 2
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QOII a saga continua Ian CastroGamboa iancastrounespbr Reações com ácidos carboxílicos Síntese de ésteres Esterificação de Fischer 2210 Reactions of Carboxylic Acids 847 Problem 2218 Draw the products of each reaction a SOCl2 OH C O CH3CH2 b 2 CH3CH22NH excess 1 SOCl2 OH O 2210B Conversion of RCOOH to RCO2O Carboxylic acids cannot be readily converted to anhydrides but dicarboxylic acids can be con verted to cyclic anhydrides by heating to high temperatures This is a dehydration reaction because a water molecule is lost from the diacid H2O H2O O O O OH OH O O OH OH O O O O O 2210C Conversion of RCOOH to RCOOR Treatment of a carboxylic acid with an alcohol in the presence of an acid catalyst forms an ester This reaction is called a Fischer esterifi cation Fischer esterification OR ROH H2SO4 H2O R OH C O R C O This reaction is an equilibrium According to Le Châteliers principle it is driven to the right by using excess alcohol or by removing the water as it is formed H2O CH3CH2OH H2O CH3OH ethyl acetate methyl benzoate H2SO4 H2SO4 CH3 OH C O CH3 OCH2CH3 C O C O OCH3 Examples C O OH The mechanism for the Fischer esterifi cation involves the usual two steps of nucleophilic acyl substitutionthat is addition of a nucleophile followed by elimination of a leaving group Because the reaction is acid catalyzed however there are additional protonation and depro tonation steps As always though the fi rst step of any mechanism with an oxygencontaining starting material and an acid is to protonate an oxygen atom as shown with a general acid HA in Mechanism 226 Ethyl acetate is a common organic solvent with a characteristic odor It is used in nail polish remover and model airplane glue smi75625ch22825879indd 847 smi75625ch22825879indd 847 111109 25841 PM 111109 25841 PM Reação geral Reações com ácidos carboxílicos Síntese de ésteres Esterificação de Fischer Catálise ácida 848 Chapter 22 Carboxylic Acids and Their DerivativesNucleophilic Acyl Substitution Esterifi cation of a carboxylic acid occurs in the presence of acid but not in the presence of base Base removes a proton from the carboxylic acid forming a carboxylate anion which does not react with an electronrich nucleophile H OH H2O ROH Both species are electron rich OH acts as a base not a nucleophile R O C O R O C O R OR C O Intramolecular esterifi cation of γ and δhydroxy carboxylic acids forms fi ve and sixmembered lactones H2SO4 O OH γ carbon γlactone δ carbon δlactone H2O H2O H2SO4 OH OH O O O OH O O Problem 2219 Draw the products of each reaction a CH3CH2OH H2SO4 COOH c NaOCH3 COOH b H2SO4 COOH OH d HO H2SO4 OH O Problem 2220 Draw the products formed when benzoic acid C6H5COOH is treated with CH3OH having its O atom labeled with 18O CH3 18OH Indicate where the labeled oxygen atom resides in the products Mechanism 226 Fischer Esterifi cationAcidCatalyzed Conversion of Carboxylic Acids to Esters Part 1 Addition of the nucleophile ROH ROH R OH OH C H 2 3 1 A A H nucleophilic addition A R OH C O R OH C OH R OH OH C RO RO H A Protonation in Step 1 makes the carbonyl group more electrophilic Nucleophilic addition of ROH forms a tetrahedral intermediate and loss of a proton forms the neutral addition product Steps 23 Part 2 Elimination of the leaving group H2O H2O 4 5 6 A A ester loss of H2O R OH OH C RO R OH OH2 C RO R OR C O H A H R OR C O H A Protonation of an OH group in Step 4 forms a good leaving group that is eliminated in Step 5 Loss of a proton in Step 6 forms the ester Only one resonance structure is drawn for the resonancestabilized cations formed in Steps 1 and 5 smi75625ch22825879indd 848 smi75625ch22825879indd 848 111109 25842 PM 111109 25842 PM 848 Chapter 22 Carboxylic Acids and Their DerivativesNucleophilic Acyl Substitution Esterifi cation of a carboxylic acid occurs in the presence of acid but not in the presence of base Base removes a proton from the carboxylic acid forming a carboxylate anion which does not react with an electronrich nucleophile H OH H2O ROH Both species are electron rich OH acts as a base not a nucleophile R O C O R O C O R OR C O Intramolecular esterifi cation of γ and δhydroxy carboxylic acids forms fi ve and sixmembered lactones H2SO4 O OH γ carbon γlactone δ carbon δlactone H2O H2O H2SO4 OH OH O O O OH O O Problem 2219 Draw the products of each reaction a CH3CH2OH H2SO4 COOH c NaOCH3 COOH b H2SO4 COOH OH d HO H2SO4 OH O Problem 2220 Draw the products formed when benzoic acid C6H5COOH is treated with CH3OH having its O atom labeled with 18O CH3 18OH Indicate where the labeled oxygen atom resides in the products Mechanism 226 Fischer Esterifi cationAcidCatalyzed Conversion of Carboxylic Acids to Esters Part 1 Addition of the nucleophile ROH ROH R OH OH C H 2 3 1 A A H nucleophilic addition A R OH C O R OH C OH R OH OH C RO RO H A Protonation in Step 1 makes the carbonyl group more electrophilic Nucleophilic addition of ROH forms a tetrahedral intermediate and loss of a proton forms the neutral addition product Steps 23 Part 2 Elimination of the leaving group H2O H2O 4 5 6 A A ester loss of H2O R OH OH C RO R OH OH2 C RO R OR C O H A H R OR C O H A Protonation of an OH group in Step 4 forms a good leaving group that is eliminated in Step 5 Loss of a proton in Step 6 forms the ester Only one resonance structure is drawn for the resonancestabilized cations formed in Steps 1 and 5 smi75625ch22825879indd 848 smi75625ch22825879indd 848 111109 25842 PM 111109 25842 PM Por quê a esterificação de Fischer não ocorre em meio básico Adição nucleofílica Perda de água Reações com ácidos carboxílicos Síntese de amidas 2210 Reactions of Carboxylic Acids 849 Problem 2221 Draw a stepwise mechanism for the following reaction H2O H2SO4 COOH HO O O 2210D Conversion of RCOOH to RCONR2 The direct conversion of a carboxylic acid to an amide with NH3 or an amine is very diffi cult even though a more reactive acyl compound is being transformed into a less reactive one The problem is that carboxylic acids are strong organic acids and NH3 and amines are bases so they undergo an acidbase reaction to form an ammonium salt before any nucleophilic substitution occurs acid base ammonium salt of a carboxylate anion H2O 1 amide H NH3 NH4 1 acidbase reaction dehydration R O C O 2 R O C O R NH2 C O Heating at high temperature 100 C dehydrates the resulting ammonium salt of the carboxylate anion to form an amide though the yield can be low Therefore the overall conversion of RCOOH to RCONH2 requires two steps 1 Acidbase reaction of RCOOH with NH3 to form an ammonium salt 2 Dehydration at high temperature 100 C 1 NH3 2 H2O C O OH C O NH2 A carboxylic acid and an amine readily react to form an amide in the presence of an additional reagent dicyclohexylcarbodiimide DCC which is converted to the byproduct dicyclohexyl urea in the course of the reaction C N dicyclohexylcarbodiimide DCC RNH2 dicyclohexylurea amide H H Amide formation using DCC a dehydrating agent H2O has been added R OH C O R NHR C O N N O N DCC is a dehydrating agent The dicyclohexylurea byproduct is formed by adding the ele ments of H2O to DCC DCC promotes amide formation by converting the carboxy OH group into a better leaving group H H DCC CH3NH2 Example CH3CH2 OH C O CH3CH2 NHCH3 C O N O N The mechanism consists of two parts 1 conversion of the OH group into a better leaving group followed by 2 addition of the nucleophile and loss of the leaving group to form the product of nucleophilic acyl substitution Mechanism 227 Amides are much more easily prepared from acid chlorides and anhydrides as discussed in Sections 228 and 229 smi75625ch22825879indd 849 smi75625ch22825879indd 849 111109 25843 PM 111109 25843 PM Reações com ácidos carboxílicos Síntese de amidas 2210 Reactions of Carboxylic Acids 849 Problem 2221 Draw a stepwise mechanism for the following reaction H2O H2SO4 COOH HO O O 2210D Conversion of RCOOH to RCONR2 The direct conversion of a carboxylic acid to an amide with NH3 or an amine is very diffi cult even though a more reactive acyl compound is being transformed into a less reactive one The problem is that carboxylic acids are strong organic acids and NH3 and amines are bases so they undergo an acidbase reaction to form an ammonium salt before any nucleophilic substitution occurs acid base ammonium salt of a carboxylate anion H2O 1 amide H NH3 NH4 1 acidbase reaction dehydration R O C O 2 R O C O R NH2 C O Heating at high temperature 100 C dehydrates the resulting ammonium salt of the carboxylate anion to form an amide though the yield can be low Therefore the overall conversion of RCOOH to RCONH2 requires two steps 1 Acidbase reaction of RCOOH with NH3 to form an ammonium salt 2 Dehydration at high temperature 100 C 1 NH3 2 H2O C O OH C O NH2 A carboxylic acid and an amine readily react to form an amide in the presence of an additional reagent dicyclohexylcarbodiimide DCC which is converted to the byproduct dicyclohexyl urea in the course of the reaction C N dicyclohexylcarbodiimide DCC RNH2 dicyclohexylurea amide H H Amide formation using DCC a dehydrating agent H2O has been added R OH C O R NHR C O N N O N DCC is a dehydrating agent The dicyclohexylurea byproduct is formed by adding the ele ments of H2O to DCC DCC promotes amide formation by converting the carboxy OH group into a better leaving group H H DCC CH3NH2 Example CH3CH2 OH C O CH3CH2 NHCH3 C O N O N The mechanism consists of two parts 1 conversion of the OH group into a better leaving group followed by 2 addition of the nucleophile and loss of the leaving group to form the product of nucleophilic acyl substitution Mechanism 227 Amides are much more easily prepared from acid chlorides and anhydrides as discussed in Sections 228 and 229 smi75625ch22825879indd 849 smi75625ch22825879indd 849 111109 25843 PM 111109 25843 PM Reações com ácidos carboxílicos Síntese de amidas 850 Chapter 22 Carboxylic Acids and Their DerivativesNucleophilic Acyl Substitution The reaction of an acid and an amine with DCC is often used in the laboratory to form the amide bond in peptides as is discussed in Chapter 28 Problem 2222 What product is formed when acetic acid is treated with each reagent a CH3NH2 b CH3NH2 then heat c CH3NH2 DCC 2211 Reactions of Esters Esters can be converted into carboxylic acids and amides Esters are hydrolyzed with water in the presence of either acid or base to form carboxylic acids or carboxylate anions carboxylic acid in acid carboxylate anion in base H2O H or OH or ROH Ester hydrolysis R OR C O R OH C O R O C O Esters react with NH3 and amines to form 1 2 or 3 amides 1 amide ROH with RNH2 with R2NH with NH3 or or 2 amide 3 amide N Reaction with nitrogen nucleophiles R OR C O R NH2 C O R NHR C O R NR2 C O Mechanism 227 Conversion of Carboxylic Acids to Amides with DCC Part 1 Conversion of OH into a better leaving group N C N δ O H 1 2 proton transfer R OH C O R C C O N N O R C C O NH N The fi rst part of the mechanism consists of two steps that convert the carboxy OH group into a better leaving group This process activates the carboxy group towards nucleophilic attack in Part 2 Part 2 Addition of the nucleophile and loss of the leaving group NH C NH O RNH2 amide 3 leaving group 4 nucleophilic attack proton transfer and elimination R NHR C O O R C C O NH N O C NH R O RNH C H N In Steps 3 and 4 nucleophilic attack of the amine on the activated carboxy group followed by elimination of dicyclohexylurea as the leaving group forms the amide smi75625ch22825879indd 850 smi75625ch22825879indd 850 111109 25844 PM 111109 25844 PM 850 Chapter 22 Carboxylic Acids and Their DerivativesNucleophilic Acyl Substitution The reaction of an acid and an amine with DCC is often used in the laboratory to form the amide bond in peptides as is discussed in Chapter 28 Problem 2222 What product is formed when acetic acid is treated with each reagent a CH3NH2 b CH3NH2 then heat c CH3NH2 DCC 2211 Reactions of Esters Esters can be converted into carboxylic acids and amides Esters are hydrolyzed with water in the presence of either acid or base to form carboxylic acids or carboxylate anions carboxylic acid in acid carboxylate anion in base H2O H or OH or ROH Ester hydrolysis R OR C O R OH C O R O C O Esters react with NH3 and amines to form 1 2 or 3 amides 1 amide ROH with RNH2 with R2NH with NH3 or or 2 amide 3 amide N Reaction with nitrogen nucleophiles R OR C O R NH2 C O R NHR C O R NR2 C O Mechanism 227 Conversion of Carboxylic Acids to Amides with DCC Part 1 Conversion of OH into a better leaving group N C N δ O H 1 2 proton transfer R OH C O R C C O N N O R C C O NH N The fi rst part of the mechanism consists of two steps that convert the carboxy OH group into a better leaving group This process activates the carboxy group towards nucleophilic attack in Part 2 Part 2 Addition of the nucleophile and loss of the leaving group NH C NH O RNH2 amide 3 leaving group 4 nucleophilic attack proton transfer and elimination R NHR C O O R C C O NH N O C NH R O RNH C H N In Steps 3 and 4 nucleophilic attack of the amine on the activated carboxy group followed by elimination of dicyclohexylurea as the leaving group forms the amide smi75625ch22825879indd 850 smi75625ch22825879indd 850 111109 25844 PM 111109 25844 PM o Nomeie o grupo acila substituindo o sufixo oico do ácido correspondente por ato o Cite o grupo alquila ligado ao oxigênio R Ésteres Nomenclatura Etanoato de etila Acetato de etila Propanoato de metila Benzoato de 2cloroetila CH3COCH2CH3 O CH3CH2COCH3 O OCH2CH2Cl O Reações com ésteres Hidrólise para síntese de ácidos carboxílicos Catálise ácida 2211 Reactions of Esters 851 2211A Ester Hydrolysis in Aqueous Acid The hydrolysis of esters in aqueous acid is a reversible equilibrium reaction that is driven to the right by using a large excess of water H2SO4 H2O CH3CH2OH CH3 OH C O CH3 OCH2CH3 C O The mechanism of ester hydrolysis in acid shown in Mechanism 228 is the reverse of the mechanism of ester synthesis from carboxylic acids Mechanism 226 Thus the mechanism consists of the addition of the nucleophile and the elimination of the leaving group the two steps common to all nucleophilic acyl substitutions as well as several proton transfers because the reaction is acidcatalyzed The fi rst step in acidcatalyzed ester hydrolysis is protonation on oxygen the same fi rst step of any mechanism involving an oxygencontaining starting material and an acid Problem 2223 In Mechanism 228 only one Lewis structure is drawn for each intermediate Draw all other resonance structures for the resonancestabilized intermediates 2211B Ester Hydrolysis in Aqueous Base Esters are hydrolyzed in aqueous base to form carboxylate anions Basic hydrolysis of an ester is called saponifi cation H2O OH CH3OH carboxylate anion C O OCH3 C O O The mechanism for this reaction has the usual two steps of the general mechanism for nucleo philic acyl substitution presented in Section 227addition of the nucleophile followed by loss of a leaving groupplus an additional step involving proton transfer Mechanism 229 Mechanism 228 AcidCatalyzed Hydrolysis of an Ester to a Carboxylic Acid Part 1 Addition of the nucleophile H2O 2 3 1 H2O HO A H A nucleophilic addition A H A R OR C O R OR C OH R OH OR C H R OH OR OH C Protonation in Step 1 makes the carbonyl group more electrophilic Nucleophilic addition of H2O forms a tetrahedral intermediate and loss of a proton forms the neutral addition product Steps 23 Part 2 Elimination of the leaving group ROH ROH A A 4 5 6 H carboxylic acid loss of ROH H A R OH OR OH C H A R OH OR OH C H R OH C O R OH C O Protonation of the OR group in Step 4 forms a good leaving group ROH that is eliminated in Step 5 Loss of a proton in Step 6 forms the carboxylic acid The word saponifi cation comes from the Latin sapo meaning soap Soap is prepared by hydrolyzing esters in fats with aqueous base as explained in Section 2212B smi75625ch22825879indd 851 smi75625ch22825879indd 851 111109 25845 PM 111109 25845 PM Reações com ésteres Hidrólise para síntese de ácidos carboxílicos Catálise ácida 2211 Reactions of Esters 851 2211A Ester Hydrolysis in Aqueous Acid The hydrolysis of esters in aqueous acid is a reversible equilibrium reaction that is driven to the right by using a large excess of water H2SO4 H2O CH3CH2OH CH3 OH C O CH3 OCH2CH3 C O The mechanism of ester hydrolysis in acid shown in Mechanism 228 is the reverse of the mechanism of ester synthesis from carboxylic acids Mechanism 226 Thus the mechanism consists of the addition of the nucleophile and the elimination of the leaving group the two steps common to all nucleophilic acyl substitutions as well as several proton transfers because the reaction is acidcatalyzed The fi rst step in acidcatalyzed ester hydrolysis is protonation on oxygen the same fi rst step of any mechanism involving an oxygencontaining starting material and an acid Problem 2223 In Mechanism 228 only one Lewis structure is drawn for each intermediate Draw all other resonance structures for the resonancestabilized intermediates 2211B Ester Hydrolysis in Aqueous Base Esters are hydrolyzed in aqueous base to form carboxylate anions Basic hydrolysis of an ester is called saponifi cation H2O OH CH3OH carboxylate anion C O OCH3 C O O The mechanism for this reaction has the usual two steps of the general mechanism for nucleo philic acyl substitution presented in Section 227addition of the nucleophile followed by loss of a leaving groupplus an additional step involving proton transfer Mechanism 229 Mechanism 228 AcidCatalyzed Hydrolysis of an Ester to a Carboxylic Acid Part 1 Addition of the nucleophile H2O 2 3 1 H2O HO A H A nucleophilic addition A H A R OR C O R OR C OH R OH OR C H R OH OR OH C Protonation in Step 1 makes the carbonyl group more electrophilic Nucleophilic addition of H2O forms a tetrahedral intermediate and loss of a proton forms the neutral addition product Steps 23 Part 2 Elimination of the leaving group ROH ROH A A 4 5 6 H carboxylic acid loss of ROH H A R OH OR OH C H A R OH OR OH C H R OH C O R OH C O Protonation of the OR group in Step 4 forms a good leaving group ROH that is eliminated in Step 5 Loss of a proton in Step 6 forms the carboxylic acid The word saponifi cation comes from the Latin sapo meaning soap Soap is prepared by hydrolyzing esters in fats with aqueous base as explained in Section 2212B smi75625ch22825879indd 851 smi75625ch22825879indd 851 111109 25845 PM 111109 25845 PM 2211 Reactions of Esters 851 2211A Ester Hydrolysis in Aqueous Acid The hydrolysis of esters in aqueous acid is a reversible equilibrium reaction that is driven to the right by using a large excess of water H2SO4 H2O CH3CH2OH CH3 OH C O CH3 OCH2CH3 C O The mechanism of ester hydrolysis in acid shown in Mechanism 228 is the reverse of the mechanism of ester synthesis from carboxylic acids Mechanism 226 Thus the mechanism consists of the addition of the nucleophile and the elimination of the leaving group the two steps common to all nucleophilic acyl substitutions as well as several proton transfers because the reaction is acidcatalyzed The fi rst step in acidcatalyzed ester hydrolysis is protonation on oxygen the same fi rst step of any mechanism involving an oxygencontaining starting material and an acid Problem 2223 In Mechanism 228 only one Lewis structure is drawn for each intermediate Draw all other resonance structures for the resonancestabilized intermediates 2211B Ester Hydrolysis in Aqueous Base Esters are hydrolyzed in aqueous base to form carboxylate anions Basic hydrolysis of an ester is called saponifi cation H2O OH CH3OH carboxylate anion C O OCH3 C O O The mechanism for this reaction has the usual two steps of the general mechanism for nucleo philic acyl substitution presented in Section 227addition of the nucleophile followed by loss of a leaving groupplus an additional step involving proton transfer Mechanism 229 Mechanism 228 AcidCatalyzed Hydrolysis of an Ester to a Carboxylic Acid Part 1 Addition of the nucleophile H2O 2 3 1 H2O HO A H A nucleophilic addition A H A R OR C O R OR C OH R OH OR C H R OH OR OH C Protonation in Step 1 makes the carbonyl group more electrophilic Nucleophilic addition of H2O forms a tetrahedral intermediate and loss of a proton forms the neutral addition product Steps 23 Part 2 Elimination of the leaving group ROH ROH A A 4 5 6 H carboxylic acid loss of ROH H A R OH OR OH C H A R OH OR OH C H R OH C O R OH C O Protonation of the OR group in Step 4 forms a good leaving group ROH that is eliminated in Step 5 Loss of a proton in Step 6 forms the carboxylic acid The word saponifi cation comes from the Latin sapo meaning soap Soap is prepared by hydrolyzing esters in fats with aqueous base as explained in Section 2212B smi75625ch22825879indd 851 smi75625ch22825879indd 851 111109 25845 PM 111109 25845 PM Reações com ésteres Hidrólise para síntese de ácidos carboxílicos Catálise básica 852 Chapter 22 Carboxylic Acids and Their DerivativesNucleophilic Acyl Substitution The carboxylate anion is resonance stabilized and this drives the equilibrium in its favor Once the reaction is complete and the carboxylate anion is formed it can be protonated with strong acid to form the neutral carboxylic acid OR RO resonancestabilized anion strong acid This bond is cleaved H2O OH R C O R O C O R O C O One O atom comes from OH R OH C O H Where do the oxygen atoms in the product come from The C OR bond in the ester is cleaved so the OR group becomes the alcohol byproduct ROH and one of the oxygens in the carbox ylate anion product comes from OH the nucleophile Problem 2224 Sunscreens that contain esters can slowly degrade over time because the ester can be hydrolyzed Draw the products formed when each commercial sunscreen undergoes hydrolysis with 1 H3O or 2 H2O OH a CH3O octinoxate O O b OH octyl salicylate O O Problem 2225 When each isotopically labeled starting material is hydrolyzed with aqueous base where does the label end up in the products a 18OCH3 C O CH3CH2 b OCH3 C CH3CH2 18O Hydrolysis is base promoted not base catalyzed because the base OH is the nucleophile that adds to the ester and forms part of the product It participates in the reaction and is not regenerated later Mechanism 229 BasePromoted Hydrolysis of an Ester to a Carboxylic Acid OH ROH tetrahedral intermediate 1 2 3 H OR carboxylate anion nucleophilic addition loss of RO proton transfer R OR C O R O OR OH C R O C O R O C O Steps 1 and 2 result in addition of the nucleophile OH followed by elimination of the leaving group OR These two steps which form the carboxylic acid are reversible because the stability of the reactants and products is comparable Next the carboxylic acid is a strong organic acid and the leaving group OR is a strong base so an acidbase reaction occurs in Step 3 to form the carboxylate anion smi75625ch22825879indd 852 smi75625ch22825879indd 852 111109 25846 PM 111109 25846 PM O que significa saponificação
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QOII a saga continua Ian CastroGamboa iancastrounespbr Reações com ácidos carboxílicos Síntese de ésteres Esterificação de Fischer 2210 Reactions of Carboxylic Acids 847 Problem 2218 Draw the products of each reaction a SOCl2 OH C O CH3CH2 b 2 CH3CH22NH excess 1 SOCl2 OH O 2210B Conversion of RCOOH to RCO2O Carboxylic acids cannot be readily converted to anhydrides but dicarboxylic acids can be con verted to cyclic anhydrides by heating to high temperatures This is a dehydration reaction because a water molecule is lost from the diacid H2O H2O O O O OH OH O O OH OH O O O O O 2210C Conversion of RCOOH to RCOOR Treatment of a carboxylic acid with an alcohol in the presence of an acid catalyst forms an ester This reaction is called a Fischer esterifi cation Fischer esterification OR ROH H2SO4 H2O R OH C O R C O This reaction is an equilibrium According to Le Châteliers principle it is driven to the right by using excess alcohol or by removing the water as it is formed H2O CH3CH2OH H2O CH3OH ethyl acetate methyl benzoate H2SO4 H2SO4 CH3 OH C O CH3 OCH2CH3 C O C O OCH3 Examples C O OH The mechanism for the Fischer esterifi cation involves the usual two steps of nucleophilic acyl substitutionthat is addition of a nucleophile followed by elimination of a leaving group Because the reaction is acid catalyzed however there are additional protonation and depro tonation steps As always though the fi rst step of any mechanism with an oxygencontaining starting material and an acid is to protonate an oxygen atom as shown with a general acid HA in Mechanism 226 Ethyl acetate is a common organic solvent with a characteristic odor It is used in nail polish remover and model airplane glue smi75625ch22825879indd 847 smi75625ch22825879indd 847 111109 25841 PM 111109 25841 PM Reação geral Reações com ácidos carboxílicos Síntese de ésteres Esterificação de Fischer Catálise ácida 848 Chapter 22 Carboxylic Acids and Their DerivativesNucleophilic Acyl Substitution Esterifi cation of a carboxylic acid occurs in the presence of acid but not in the presence of base Base removes a proton from the carboxylic acid forming a carboxylate anion which does not react with an electronrich nucleophile H OH H2O ROH Both species are electron rich OH acts as a base not a nucleophile R O C O R O C O R OR C O Intramolecular esterifi cation of γ and δhydroxy carboxylic acids forms fi ve and sixmembered lactones H2SO4 O OH γ carbon γlactone δ carbon δlactone H2O H2O H2SO4 OH OH O O O OH O O Problem 2219 Draw the products of each reaction a CH3CH2OH H2SO4 COOH c NaOCH3 COOH b H2SO4 COOH OH d HO H2SO4 OH O Problem 2220 Draw the products formed when benzoic acid C6H5COOH is treated with CH3OH having its O atom labeled with 18O CH3 18OH Indicate where the labeled oxygen atom resides in the products Mechanism 226 Fischer Esterifi cationAcidCatalyzed Conversion of Carboxylic Acids to Esters Part 1 Addition of the nucleophile ROH ROH R OH OH C H 2 3 1 A A H nucleophilic addition A R OH C O R OH C OH R OH OH C RO RO H A Protonation in Step 1 makes the carbonyl group more electrophilic Nucleophilic addition of ROH forms a tetrahedral intermediate and loss of a proton forms the neutral addition product Steps 23 Part 2 Elimination of the leaving group H2O H2O 4 5 6 A A ester loss of H2O R OH OH C RO R OH OH2 C RO R OR C O H A H R OR C O H A Protonation of an OH group in Step 4 forms a good leaving group that is eliminated in Step 5 Loss of a proton in Step 6 forms the ester Only one resonance structure is drawn for the resonancestabilized cations formed in Steps 1 and 5 smi75625ch22825879indd 848 smi75625ch22825879indd 848 111109 25842 PM 111109 25842 PM 848 Chapter 22 Carboxylic Acids and Their DerivativesNucleophilic Acyl Substitution Esterifi cation of a carboxylic acid occurs in the presence of acid but not in the presence of base Base removes a proton from the carboxylic acid forming a carboxylate anion which does not react with an electronrich nucleophile H OH H2O ROH Both species are electron rich OH acts as a base not a nucleophile R O C O R O C O R OR C O Intramolecular esterifi cation of γ and δhydroxy carboxylic acids forms fi ve and sixmembered lactones H2SO4 O OH γ carbon γlactone δ carbon δlactone H2O H2O H2SO4 OH OH O O O OH O O Problem 2219 Draw the products of each reaction a CH3CH2OH H2SO4 COOH c NaOCH3 COOH b H2SO4 COOH OH d HO H2SO4 OH O Problem 2220 Draw the products formed when benzoic acid C6H5COOH is treated with CH3OH having its O atom labeled with 18O CH3 18OH Indicate where the labeled oxygen atom resides in the products Mechanism 226 Fischer Esterifi cationAcidCatalyzed Conversion of Carboxylic Acids to Esters Part 1 Addition of the nucleophile ROH ROH R OH OH C H 2 3 1 A A H nucleophilic addition A R OH C O R OH C OH R OH OH C RO RO H A Protonation in Step 1 makes the carbonyl group more electrophilic Nucleophilic addition of ROH forms a tetrahedral intermediate and loss of a proton forms the neutral addition product Steps 23 Part 2 Elimination of the leaving group H2O H2O 4 5 6 A A ester loss of H2O R OH OH C RO R OH OH2 C RO R OR C O H A H R OR C O H A Protonation of an OH group in Step 4 forms a good leaving group that is eliminated in Step 5 Loss of a proton in Step 6 forms the ester Only one resonance structure is drawn for the resonancestabilized cations formed in Steps 1 and 5 smi75625ch22825879indd 848 smi75625ch22825879indd 848 111109 25842 PM 111109 25842 PM Por quê a esterificação de Fischer não ocorre em meio básico Adição nucleofílica Perda de água Reações com ácidos carboxílicos Síntese de amidas 2210 Reactions of Carboxylic Acids 849 Problem 2221 Draw a stepwise mechanism for the following reaction H2O H2SO4 COOH HO O O 2210D Conversion of RCOOH to RCONR2 The direct conversion of a carboxylic acid to an amide with NH3 or an amine is very diffi cult even though a more reactive acyl compound is being transformed into a less reactive one The problem is that carboxylic acids are strong organic acids and NH3 and amines are bases so they undergo an acidbase reaction to form an ammonium salt before any nucleophilic substitution occurs acid base ammonium salt of a carboxylate anion H2O 1 amide H NH3 NH4 1 acidbase reaction dehydration R O C O 2 R O C O R NH2 C O Heating at high temperature 100 C dehydrates the resulting ammonium salt of the carboxylate anion to form an amide though the yield can be low Therefore the overall conversion of RCOOH to RCONH2 requires two steps 1 Acidbase reaction of RCOOH with NH3 to form an ammonium salt 2 Dehydration at high temperature 100 C 1 NH3 2 H2O C O OH C O NH2 A carboxylic acid and an amine readily react to form an amide in the presence of an additional reagent dicyclohexylcarbodiimide DCC which is converted to the byproduct dicyclohexyl urea in the course of the reaction C N dicyclohexylcarbodiimide DCC RNH2 dicyclohexylurea amide H H Amide formation using DCC a dehydrating agent H2O has been added R OH C O R NHR C O N N O N DCC is a dehydrating agent The dicyclohexylurea byproduct is formed by adding the ele ments of H2O to DCC DCC promotes amide formation by converting the carboxy OH group into a better leaving group H H DCC CH3NH2 Example CH3CH2 OH C O CH3CH2 NHCH3 C O N O N The mechanism consists of two parts 1 conversion of the OH group into a better leaving group followed by 2 addition of the nucleophile and loss of the leaving group to form the product of nucleophilic acyl substitution Mechanism 227 Amides are much more easily prepared from acid chlorides and anhydrides as discussed in Sections 228 and 229 smi75625ch22825879indd 849 smi75625ch22825879indd 849 111109 25843 PM 111109 25843 PM Reações com ácidos carboxílicos Síntese de amidas 2210 Reactions of Carboxylic Acids 849 Problem 2221 Draw a stepwise mechanism for the following reaction H2O H2SO4 COOH HO O O 2210D Conversion of RCOOH to RCONR2 The direct conversion of a carboxylic acid to an amide with NH3 or an amine is very diffi cult even though a more reactive acyl compound is being transformed into a less reactive one The problem is that carboxylic acids are strong organic acids and NH3 and amines are bases so they undergo an acidbase reaction to form an ammonium salt before any nucleophilic substitution occurs acid base ammonium salt of a carboxylate anion H2O 1 amide H NH3 NH4 1 acidbase reaction dehydration R O C O 2 R O C O R NH2 C O Heating at high temperature 100 C dehydrates the resulting ammonium salt of the carboxylate anion to form an amide though the yield can be low Therefore the overall conversion of RCOOH to RCONH2 requires two steps 1 Acidbase reaction of RCOOH with NH3 to form an ammonium salt 2 Dehydration at high temperature 100 C 1 NH3 2 H2O C O OH C O NH2 A carboxylic acid and an amine readily react to form an amide in the presence of an additional reagent dicyclohexylcarbodiimide DCC which is converted to the byproduct dicyclohexyl urea in the course of the reaction C N dicyclohexylcarbodiimide DCC RNH2 dicyclohexylurea amide H H Amide formation using DCC a dehydrating agent H2O has been added R OH C O R NHR C O N N O N DCC is a dehydrating agent The dicyclohexylurea byproduct is formed by adding the ele ments of H2O to DCC DCC promotes amide formation by converting the carboxy OH group into a better leaving group H H DCC CH3NH2 Example CH3CH2 OH C O CH3CH2 NHCH3 C O N O N The mechanism consists of two parts 1 conversion of the OH group into a better leaving group followed by 2 addition of the nucleophile and loss of the leaving group to form the product of nucleophilic acyl substitution Mechanism 227 Amides are much more easily prepared from acid chlorides and anhydrides as discussed in Sections 228 and 229 smi75625ch22825879indd 849 smi75625ch22825879indd 849 111109 25843 PM 111109 25843 PM Reações com ácidos carboxílicos Síntese de amidas 850 Chapter 22 Carboxylic Acids and Their DerivativesNucleophilic Acyl Substitution The reaction of an acid and an amine with DCC is often used in the laboratory to form the amide bond in peptides as is discussed in Chapter 28 Problem 2222 What product is formed when acetic acid is treated with each reagent a CH3NH2 b CH3NH2 then heat c CH3NH2 DCC 2211 Reactions of Esters Esters can be converted into carboxylic acids and amides Esters are hydrolyzed with water in the presence of either acid or base to form carboxylic acids or carboxylate anions carboxylic acid in acid carboxylate anion in base H2O H or OH or ROH Ester hydrolysis R OR C O R OH C O R O C O Esters react with NH3 and amines to form 1 2 or 3 amides 1 amide ROH with RNH2 with R2NH with NH3 or or 2 amide 3 amide N Reaction with nitrogen nucleophiles R OR C O R NH2 C O R NHR C O R NR2 C O Mechanism 227 Conversion of Carboxylic Acids to Amides with DCC Part 1 Conversion of OH into a better leaving group N C N δ O H 1 2 proton transfer R OH C O R C C O N N O R C C O NH N The fi rst part of the mechanism consists of two steps that convert the carboxy OH group into a better leaving group This process activates the carboxy group towards nucleophilic attack in Part 2 Part 2 Addition of the nucleophile and loss of the leaving group NH C NH O RNH2 amide 3 leaving group 4 nucleophilic attack proton transfer and elimination R NHR C O O R C C O NH N O C NH R O RNH C H N In Steps 3 and 4 nucleophilic attack of the amine on the activated carboxy group followed by elimination of dicyclohexylurea as the leaving group forms the amide smi75625ch22825879indd 850 smi75625ch22825879indd 850 111109 25844 PM 111109 25844 PM 850 Chapter 22 Carboxylic Acids and Their DerivativesNucleophilic Acyl Substitution The reaction of an acid and an amine with DCC is often used in the laboratory to form the amide bond in peptides as is discussed in Chapter 28 Problem 2222 What product is formed when acetic acid is treated with each reagent a CH3NH2 b CH3NH2 then heat c CH3NH2 DCC 2211 Reactions of Esters Esters can be converted into carboxylic acids and amides Esters are hydrolyzed with water in the presence of either acid or base to form carboxylic acids or carboxylate anions carboxylic acid in acid carboxylate anion in base H2O H or OH or ROH Ester hydrolysis R OR C O R OH C O R O C O Esters react with NH3 and amines to form 1 2 or 3 amides 1 amide ROH with RNH2 with R2NH with NH3 or or 2 amide 3 amide N Reaction with nitrogen nucleophiles R OR C O R NH2 C O R NHR C O R NR2 C O Mechanism 227 Conversion of Carboxylic Acids to Amides with DCC Part 1 Conversion of OH into a better leaving group N C N δ O H 1 2 proton transfer R OH C O R C C O N N O R C C O NH N The fi rst part of the mechanism consists of two steps that convert the carboxy OH group into a better leaving group This process activates the carboxy group towards nucleophilic attack in Part 2 Part 2 Addition of the nucleophile and loss of the leaving group NH C NH O RNH2 amide 3 leaving group 4 nucleophilic attack proton transfer and elimination R NHR C O O R C C O NH N O C NH R O RNH C H N In Steps 3 and 4 nucleophilic attack of the amine on the activated carboxy group followed by elimination of dicyclohexylurea as the leaving group forms the amide smi75625ch22825879indd 850 smi75625ch22825879indd 850 111109 25844 PM 111109 25844 PM o Nomeie o grupo acila substituindo o sufixo oico do ácido correspondente por ato o Cite o grupo alquila ligado ao oxigênio R Ésteres Nomenclatura Etanoato de etila Acetato de etila Propanoato de metila Benzoato de 2cloroetila CH3COCH2CH3 O CH3CH2COCH3 O OCH2CH2Cl O Reações com ésteres Hidrólise para síntese de ácidos carboxílicos Catálise ácida 2211 Reactions of Esters 851 2211A Ester Hydrolysis in Aqueous Acid The hydrolysis of esters in aqueous acid is a reversible equilibrium reaction that is driven to the right by using a large excess of water H2SO4 H2O CH3CH2OH CH3 OH C O CH3 OCH2CH3 C O The mechanism of ester hydrolysis in acid shown in Mechanism 228 is the reverse of the mechanism of ester synthesis from carboxylic acids Mechanism 226 Thus the mechanism consists of the addition of the nucleophile and the elimination of the leaving group the two steps common to all nucleophilic acyl substitutions as well as several proton transfers because the reaction is acidcatalyzed The fi rst step in acidcatalyzed ester hydrolysis is protonation on oxygen the same fi rst step of any mechanism involving an oxygencontaining starting material and an acid Problem 2223 In Mechanism 228 only one Lewis structure is drawn for each intermediate Draw all other resonance structures for the resonancestabilized intermediates 2211B Ester Hydrolysis in Aqueous Base Esters are hydrolyzed in aqueous base to form carboxylate anions Basic hydrolysis of an ester is called saponifi cation H2O OH CH3OH carboxylate anion C O OCH3 C O O The mechanism for this reaction has the usual two steps of the general mechanism for nucleo philic acyl substitution presented in Section 227addition of the nucleophile followed by loss of a leaving groupplus an additional step involving proton transfer Mechanism 229 Mechanism 228 AcidCatalyzed Hydrolysis of an Ester to a Carboxylic Acid Part 1 Addition of the nucleophile H2O 2 3 1 H2O HO A H A nucleophilic addition A H A R OR C O R OR C OH R OH OR C H R OH OR OH C Protonation in Step 1 makes the carbonyl group more electrophilic Nucleophilic addition of H2O forms a tetrahedral intermediate and loss of a proton forms the neutral addition product Steps 23 Part 2 Elimination of the leaving group ROH ROH A A 4 5 6 H carboxylic acid loss of ROH H A R OH OR OH C H A R OH OR OH C H R OH C O R OH C O Protonation of the OR group in Step 4 forms a good leaving group ROH that is eliminated in Step 5 Loss of a proton in Step 6 forms the carboxylic acid The word saponifi cation comes from the Latin sapo meaning soap Soap is prepared by hydrolyzing esters in fats with aqueous base as explained in Section 2212B smi75625ch22825879indd 851 smi75625ch22825879indd 851 111109 25845 PM 111109 25845 PM Reações com ésteres Hidrólise para síntese de ácidos carboxílicos Catálise ácida 2211 Reactions of Esters 851 2211A Ester Hydrolysis in Aqueous Acid The hydrolysis of esters in aqueous acid is a reversible equilibrium reaction that is driven to the right by using a large excess of water H2SO4 H2O CH3CH2OH CH3 OH C O CH3 OCH2CH3 C O The mechanism of ester hydrolysis in acid shown in Mechanism 228 is the reverse of the mechanism of ester synthesis from carboxylic acids Mechanism 226 Thus the mechanism consists of the addition of the nucleophile and the elimination of the leaving group the two steps common to all nucleophilic acyl substitutions as well as several proton transfers because the reaction is acidcatalyzed The fi rst step in acidcatalyzed ester hydrolysis is protonation on oxygen the same fi rst step of any mechanism involving an oxygencontaining starting material and an acid Problem 2223 In Mechanism 228 only one Lewis structure is drawn for each intermediate Draw all other resonance structures for the resonancestabilized intermediates 2211B Ester Hydrolysis in Aqueous Base Esters are hydrolyzed in aqueous base to form carboxylate anions Basic hydrolysis of an ester is called saponifi cation H2O OH CH3OH carboxylate anion C O OCH3 C O O The mechanism for this reaction has the usual two steps of the general mechanism for nucleo philic acyl substitution presented in Section 227addition of the nucleophile followed by loss of a leaving groupplus an additional step involving proton transfer Mechanism 229 Mechanism 228 AcidCatalyzed Hydrolysis of an Ester to a Carboxylic Acid Part 1 Addition of the nucleophile H2O 2 3 1 H2O HO A H A nucleophilic addition A H A R OR C O R OR C OH R OH OR C H R OH OR OH C Protonation in Step 1 makes the carbonyl group more electrophilic Nucleophilic addition of H2O forms a tetrahedral intermediate and loss of a proton forms the neutral addition product Steps 23 Part 2 Elimination of the leaving group ROH ROH A A 4 5 6 H carboxylic acid loss of ROH H A R OH OR OH C H A R OH OR OH C H R OH C O R OH C O Protonation of the OR group in Step 4 forms a good leaving group ROH that is eliminated in Step 5 Loss of a proton in Step 6 forms the carboxylic acid The word saponifi cation comes from the Latin sapo meaning soap Soap is prepared by hydrolyzing esters in fats with aqueous base as explained in Section 2212B smi75625ch22825879indd 851 smi75625ch22825879indd 851 111109 25845 PM 111109 25845 PM 2211 Reactions of Esters 851 2211A Ester Hydrolysis in Aqueous Acid The hydrolysis of esters in aqueous acid is a reversible equilibrium reaction that is driven to the right by using a large excess of water H2SO4 H2O CH3CH2OH CH3 OH C O CH3 OCH2CH3 C O The mechanism of ester hydrolysis in acid shown in Mechanism 228 is the reverse of the mechanism of ester synthesis from carboxylic acids Mechanism 226 Thus the mechanism consists of the addition of the nucleophile and the elimination of the leaving group the two steps common to all nucleophilic acyl substitutions as well as several proton transfers because the reaction is acidcatalyzed The fi rst step in acidcatalyzed ester hydrolysis is protonation on oxygen the same fi rst step of any mechanism involving an oxygencontaining starting material and an acid Problem 2223 In Mechanism 228 only one Lewis structure is drawn for each intermediate Draw all other resonance structures for the resonancestabilized intermediates 2211B Ester Hydrolysis in Aqueous Base Esters are hydrolyzed in aqueous base to form carboxylate anions Basic hydrolysis of an ester is called saponifi cation H2O OH CH3OH carboxylate anion C O OCH3 C O O The mechanism for this reaction has the usual two steps of the general mechanism for nucleo philic acyl substitution presented in Section 227addition of the nucleophile followed by loss of a leaving groupplus an additional step involving proton transfer Mechanism 229 Mechanism 228 AcidCatalyzed Hydrolysis of an Ester to a Carboxylic Acid Part 1 Addition of the nucleophile H2O 2 3 1 H2O HO A H A nucleophilic addition A H A R OR C O R OR C OH R OH OR C H R OH OR OH C Protonation in Step 1 makes the carbonyl group more electrophilic Nucleophilic addition of H2O forms a tetrahedral intermediate and loss of a proton forms the neutral addition product Steps 23 Part 2 Elimination of the leaving group ROH ROH A A 4 5 6 H carboxylic acid loss of ROH H A R OH OR OH C H A R OH OR OH C H R OH C O R OH C O Protonation of the OR group in Step 4 forms a good leaving group ROH that is eliminated in Step 5 Loss of a proton in Step 6 forms the carboxylic acid The word saponifi cation comes from the Latin sapo meaning soap Soap is prepared by hydrolyzing esters in fats with aqueous base as explained in Section 2212B smi75625ch22825879indd 851 smi75625ch22825879indd 851 111109 25845 PM 111109 25845 PM Reações com ésteres Hidrólise para síntese de ácidos carboxílicos Catálise básica 852 Chapter 22 Carboxylic Acids and Their DerivativesNucleophilic Acyl Substitution The carboxylate anion is resonance stabilized and this drives the equilibrium in its favor Once the reaction is complete and the carboxylate anion is formed it can be protonated with strong acid to form the neutral carboxylic acid OR RO resonancestabilized anion strong acid This bond is cleaved H2O OH R C O R O C O R O C O One O atom comes from OH R OH C O H Where do the oxygen atoms in the product come from The C OR bond in the ester is cleaved so the OR group becomes the alcohol byproduct ROH and one of the oxygens in the carbox ylate anion product comes from OH the nucleophile Problem 2224 Sunscreens that contain esters can slowly degrade over time because the ester can be hydrolyzed Draw the products formed when each commercial sunscreen undergoes hydrolysis with 1 H3O or 2 H2O OH a CH3O octinoxate O O b OH octyl salicylate O O Problem 2225 When each isotopically labeled starting material is hydrolyzed with aqueous base where does the label end up in the products a 18OCH3 C O CH3CH2 b OCH3 C CH3CH2 18O Hydrolysis is base promoted not base catalyzed because the base OH is the nucleophile that adds to the ester and forms part of the product It participates in the reaction and is not regenerated later Mechanism 229 BasePromoted Hydrolysis of an Ester to a Carboxylic Acid OH ROH tetrahedral intermediate 1 2 3 H OR carboxylate anion nucleophilic addition loss of RO proton transfer R OR C O R O OR OH C R O C O R O C O Steps 1 and 2 result in addition of the nucleophile OH followed by elimination of the leaving group OR These two steps which form the carboxylic acid are reversible because the stability of the reactants and products is comparable Next the carboxylic acid is a strong organic acid and the leaving group OR is a strong base so an acidbase reaction occurs in Step 3 to form the carboxylate anion smi75625ch22825879indd 852 smi75625ch22825879indd 852 111109 25846 PM 111109 25846 PM O que significa saponificação