CHAPTER 20 CARBOXYLIC ACID DERIVATIVES NUCLEOPHILIC ACYL SUBSTITUTION SOLUTIONS TO TEXT PROBLEMS 20.1 (b) Carboxylic acid anhydrides bear two acyl groups on oxygen, as in RCOCR. They are named as derivatives of carboxylic acid CH CH.CHCOH CH CH..CH C6Hs C6H 2-Phenylbutanoic acid 2-Phenylbutanoic anhydride (c) Butyl 2-phenylbutanoate is the butyl ester of 2-phenylbutanoic acid CHCH, CHCOCH, CH, CH,CH (d) In 2-phenylbutyl butanoate the 2-phenylbutyl group is an alkyl group bonded to oxygen of the ester. It is not involved in the acyl group of the molecule CH, CH,CH,COCH,CHCH, CH 2-Phenylbutyl butanoate 536 Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
CHAPTER 20 CARBOXYLIC ACID DERIVATIVES: NUCLEOPHILIC ACYL SUBSTITUTION SOLUTIONS TO TEXT PROBLEMS 20.1 (b) Carboxylic acid anhydrides bear two acyl groups on oxygen, as in . They are named as derivatives of carboxylic acids. (c) Butyl 2-phenylbutanoate is the butyl ester of 2-phenylbutanoic acid. (d) In 2-phenylbutyl butanoate the 2-phenylbutyl group is an alkyl group bonded to oxygen of the ester. It is not involved in the acyl group of the molecule. CH3CH2CH2COCH2CHCH2CH3 O C6H5 2-Phenylbutyl butanoate CH3CH2CHCOCH2CH2CH2CH3 O C6H5 Butyl 2-phenylbutanoate CH3CH2CHCOCCHCH2CH3 O O C6H5 C6H5 CH3CH2CHCOH O C6H5 2-Phenylbutanoic acid 2-Phenylbutanoic anhydride RCOCR O O 536 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CARBOXYLIC ACID DERIVATIVES: NUCLEOPHILIC ACYL SUBSTITUTION 537 (e) The ending -amide reveals this to be a compound of the type RCNH, CH3,CHCNH CAH 2-Phenylbutanamide (f) This compound differs from 2-phenylbutanamide in part(e)only in that it bears an ethyl sub- sutuent on nitrogen CHa CH, CHCNHCH, CH CH N-Ethyl-2-Phenylbutanamide (g) The -nitrile ending signifies a compound of the type RC=N containing the same number of carbons as the alkane rch CH2 CH. CHO≡N CH 2-Phenylbutanenitrile 20.2 The methyl groups in N, N-dimethylformamide are nonequivalent: one is cis to oxygen, the other is trans. The two methyl groups have different chemical shifts. CH CH3 Rotation about the carbon-nitrogen bond is required to average the environments of the two methyl groups, but this rotation is relatively slow in amides as the result of the double-bond character im parted to the carbon-nitrogen bond, as shown by these two resonance structures 20.3(b) Benzoyl chloride reacts with benzoic acid to give benzoic anhydride C6H- CCI C6HSCOH CBHSCOCC H5 HCI Benzoic acid Benzoic anhydride Hydrogen (c) Acyl chlorides react with alcohols to form esters C6H CCI CH3 CH,OH- C6H_ COCH, CH3 HCI Benzoyl Ethanol chloride The organic product is the ethyl ester of benzoic acid, ethyl benzoate. Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
CARBOXYLIC ACID DERIVATIVES: NUCLEOPHILIC ACYL SUBSTITUTION 537 (e) The ending -amide reveals this to be a compound of the type . ( f ) This compound differs from 2-phenylbutanamide in part (e) only in that it bears an ethyl substituent on nitrogen. (g) The -nitrile ending signifies a compound of the type RC>N containing the same number of carbons as the alkane RCH3. 20.2 The methyl groups in N,N-dimethylformamide are nonequivalent; one is cis to oxygen, the other is trans. The two methyl groups have different chemical shifts. Rotation about the carbon–nitrogen bond is required to average the environments of the two methyl groups, but this rotation is relatively slow in amides as the result of the double-bond character imparted to the carbon–nitrogen bond, as shown by these two resonance structures. 20.3 (b) Benzoyl chloride reacts with benzoic acid to give benzoic anhydride. (c) Acyl chlorides react with alcohols to form esters. The organic product is the ethyl ester of benzoic acid, ethyl benzoate. C6H5CCl O Benzoyl chloride CH3CH2OH Ethanol C6H5COCH2CH3 O Ethyl benzoate HCl Hydrogen chloride C6H5CCl O Benzoyl chloride C6H5COH O Benzoic acid C6H5COCC6H5 O O Benzoic anhydride HCl Hydrogen chloride C H O N CH3 CH3 C H O N CH3 CH3 2-Phenylbutanenitrile CH3CH2CHC N C6H5 CH3CH2CHCNHCH2CH3 O C6H5 N-Ethyl-2-phenylbutanamide CH3CH2CHCNH2 O C6H5 2-Phenylbutanamide RCNH2 O Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
538 CARBOXYLIC ACID DERIVATIVES: NUCLEOPHILIC ACYL SUBSTITUTION (d) Acyl transfer from benzoyl chloride to the nitrogen of methylamine yields the amide N-methyl C6HsCCI 2CH,NH C6HSCNHCH3 CHaNH3 CI Benzoyl Methy lamine N-Methy benzamide chloride (e) In analogy with part(d), an amide is formed. In this case the product has two methyl groups CI t 2(CH)2NH H3)2+(CH3)2NH2 (f) Acyl chlorides undergo hydrolysis on reaction with water. The product is a carboxylic acid CsH +H2O—CH5COH+HCl Hyd chloride 20.4(b) Nucleophilic addition of benzoic acid to benzoyl chloride gives the tetrahedral intermediate own C6HsCCI CH COH C6H-COCC6H5 Benzoic acid Dissociation of the tetrahedral intermediate occurs by loss of chloride and of the proton on the oxygen. C6H-COCC6H5 C6H COCC6H5 HCI Tetrahedral intermediate Benzoic anhydrid chloride (c) Ethanol is the nucleophile that adds to the carbonyl group of benzoyl chloride to form the tetrahedral intermediate C6HSCCI CH, CH,OH C6H, CH3 Ethanol Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
538 CARBOXYLIC ACID DERIVATIVES: NUCLEOPHILIC ACYL SUBSTITUTION (d) Acyl transfer from benzoyl chloride to the nitrogen of methylamine yields the amide N-methylbenzamide. (e) In analogy with part (d), an amide is formed. In this case the product has two methyl groups on nitrogen. ( f) Acyl chlorides undergo hydrolysis on reaction with water. The product is a carboxylic acid. 20.4 (b) Nucleophilic addition of benzoic acid to benzoyl chloride gives the tetrahedral intermediate shown. Dissociation of the tetrahedral intermediate occurs by loss of chloride and of the proton on the oxygen. (c) Ethanol is the nucleophile that adds to the carbonyl group of benzoyl chloride to form the tetrahedral intermediate. C6H5CCl O Benzoyl chloride CH3CH2OH Ethanol Tetrahedral intermediate C6H5COCH2CH3 OH Cl C6H5COCC6H5 O O Benzoic anhydride HCl Hydrogen chloride Tetrahedral intermediate C6H5COCC6H5 O H Cl O C6H5CCl O Benzoyl chloride C6H5COH O Benzoic acid C6H5COCC6H5 HO Cl O Tetrahedral intermediate C6H5CCl O Benzoyl chloride H2O Water C6H5COH O Benzoic acid HCl Hydrogen chloride C6H5CCl O Benzoyl chloride 2(CH3)2NH Dimethylamine C6H5CN(CH3)2 O N,N-Dimethylbenzamide (CH3)2NH2 Cl C6H5CCl O Benzoyl chloride 2CH3NH2 Methylamine C6H5CNHCH3 O N-Methylbenzamide CH3NH3 Cl Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CARBOXYLIC ACID DERIVATIVES: NUCLEOPHILIC ACYL SU BSTITUTION 539 In analogy with parts(a) and(b)of this problem, a proton is lost from the hydroxyl group along with chloride to restore the carbon-oxygen double bond CsHSCOCH,CH 6H5 COCH, CH3 HCI Tetrahedral intermediate Ethyl benzoate Hydrogen (d) The tetrahedral intermediate formed from benzoyl chloride and methylamine has a carbon- C6HSCCI CH,NH2 C6H-CNHCH3 Benzoyl Methylamine Tetrahedral intermediate The dissociation of the tetrahedral intermediate may be shown as CBHSCNHCH C6HSCNHCH3 HCl Tetrahedral intermediate More realistically, it is a second methylamine molecule that abstracts a proton from oxygen CH3NH C6HSCNHCH C6HSCNHCH3 CH3NH, CI N-Methylbenzamide Methylammonium chloride (e) The intermediates in the reaction of benzoyl chloride with dimethy lamine are similar to those n part(d). The methyl substituents on nitrogen are not directly involved in the reaction. C6H- CCI (CH,)2NH C6H5CN(CH3) 2 Tetrahedral intermediate Then (CH3)2NH C6HSCN(CH3)2 C6HSCN(CH3) (CH3)2NH, CI N,N-Dimethylbenzamide Dimethylammonium chloride Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
In analogy with parts (a) and (b) of this problem, a proton is lost from the hydroxyl group along with chloride to restore the carbon–oxygen double bond. (d) The tetrahedral intermediate formed from benzoyl chloride and methylamine has a carbon– nitrogen bond. The dissociation of the tetrahedral intermediate may be shown as More realistically, it is a second methylamine molecule that abstracts a proton from oxygen. (e) The intermediates in the reaction of benzoyl chloride with dimethylamine are similar to those in part (d). The methyl substituents on nitrogen are not directly involved in the reaction. Then C6H5CN(CH3)2 O N,N-Dimethylbenzamide Dimethylammonium chloride (CH3)2NH2 Cl C6H5CN(CH3)2 O H Cl (CH3)2NH C6H5CCl O Benzoyl chloride (CH3)2NH Dimethylamine Tetrahedral intermediate C6H5CN(CH3)2 OH Cl C6H5CNHCH3 O N-Methylbenzamide Methylammonium chloride CH3NH3 Cl C6H5CNHCH3 O H Cl CH3NH2 C6H5CNHCH3 O N-Methylbenzamide HCl Hydrogen chloride Tetrahedral intermediate C6H5CNHCH3 O H Cl C6H5CCl O Benzoyl chloride CH3NH2 Methylamine Tetrahedral intermediate C6H5CNHCH3 OH Cl C6H5COCH2CH3 O Ethyl benzoate HCl Hydrogen chloride Tetrahedral intermediate C6H5COCH2CH3 O H Cl CARBOXYLIC ACID DERIVATIVES: NUCLEOPHILIC ACYL SUBSTITUTION 539 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
540 CARBOXYLIC ACID DERIVATIVES: NUCLEOPHILIC ACYL SUBSTITUTION (f) Water attacks the carbonyl group of benzoyl chloride to form the tetrahedral intermediate CsH CCI H,O CH-CCI tetrahedral oride Dissociation of the tetrahedral intermediate occurs by loss of chloride and the proton on C6HSCOH HCI Benzoic acid 20.5 One equivalent of benzoyl chloride reacts rapidly with water to yield benzoic acid C6HSCCI H,O C6HSCOH HCI Hydrogen chloride The benzoic acid produced in this step reacts with the remaining benzoyl chloride to give benzoic anhydride C6HSCCI CBH_ COH CBH_COCC H5 HCl enz Benzoic acid Benzoic anhydride Hydrogen 20.6 Acetic anhydride serves as a source of acetyl cation CH, CO-CCH3 CCH O≡CCH Acetyl catio 20.7(b) Acyl transfer from an acid anhydride to ammonia yields an amide. 00 CH, COCCH3 2NH, CHaCNH,+ CH3 CO NH4 Acetic anhydride ammonia etamide Ammonium acetate The organic products are acetamide and ammonium acetate Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
( f) Water attacks the carbonyl group of benzoyl chloride to form the tetrahedral intermediate. Dissociation of the tetrahedral intermediate occurs by loss of chloride and the proton on oxygen. 20.5 One equivalent of benzoyl chloride reacts rapidly with water to yield benzoic acid. The benzoic acid produced in this step reacts with the remaining benzoyl chloride to give benzoic anhydride. 20.6 Acetic anhydride serves as a source of acetyl cation. 20.7 (b) Acyl transfer from an acid anhydride to ammonia yields an amide. The organic products are acetamide and ammonium acetate. Acetic anhydride CH3COCCH3 O O 2NH3 Ammonia CH3CNH2 O Acetamide CH3CO NH4 O Ammonium acetate Acetyl cation CH3CO O CCH3 O O CCH3 O CCH3 HCl Hydrogen chloride C6H5COCC6H5 O O Benzoic anhydride C6H5CCl O Benzoyl chloride C6H5COH O Benzoic acid H2O Water C6H5CCl O Benzoyl chloride HCl Hydrogen chloride C6H5COH O Benzoic acid HCl Hydrogen chloride C6H5COH O Tetrahedral Benzoic acid intermediate C6H5C Cl O H OH C6H5CCl O Benzoyl chloride H2O Water Tetrahedral intermediate C6H5CCl OH OH 540 CARBOXYLIC ACID DERIVATIVES: NUCLEOPHILIC ACYL SUBSTITUTION Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website