Medical Chemistry Seminar 2024 PDF

Week 12 Medical Chemistry Seminar 2024 Carboxylic Acids Derivatives Department of Medical Chemistry UD Faculty of Medicine  Anhydride Ester CAR...

Week 12 Medical Chemistry Seminar 2024 Carboxylic Acids Derivatives Department of Medical Chemistry UD Faculty of Medicine  Anhydride Ester CARBOXYLIC ACID DERIVATIVES O O List major types of carboxylic acid derivatives. R C O R' R C NH2 Ester Amide O O O O R C Cl R CO O C R' RO C OR' H R C NH R C N R' acid halide anhydride 2 ester Amide N-substituted amide O O O R" H R C NH2 R C N R' R C N R' primary N-substituted secondaryamide N,N-disubstituted tertiary amide amides O R"  CARBOXYLIC ACID DERIVATIVES: ACYL HALIDES ACYL GROUPS IUPAC O an acyl group R C -oyl Common O ethanoyl -yl CH3 C acetyl ACID HALIDES O O O C CH3CH2CH2 C CH3 C Cl Cl Cl butanoyl chloride ethanoyl chloride benzoyl chloride butyryl chloride acetyl chloride  Formation of acyl halides Acid chlorides of inorganic acids are used to prepare organic acid chlorides. O O PCl5 R C R C ACYL HALIDE OH Cl complete the following chemical reaction: Butanoic acid+SOCl2 (thionyl chloride) SOCl2 O CH3-CH2-CH2-C- O CH3CH2CH2C OH Cl butanoyl chloride ben butyryl chloride HALIDES Name of the acyl group + halide Give the name of the following molecules. O CH3CH2CH2 C Cl O CH3 C Cl HALIDES Name of the acyl group + halide Give the name of the following molecules. O CH3CH2CH2 C Cl butanoyl chloride Benzoyl bromide Cyclohexanecarbonyl butyryl chloride chloride O CH3 C Cl ethanoyl chloride 4-methylpentanoyl chloride acetyl chloride CARBOXYLIC ACID DERIVATIVES: SALTS OF ACIDS Carboxylic acids react with bases to form ionic salts O CH3CH2CH2CH2 C - + metal -oate O Na sodium pentanoate O - + potassium benzoate O K potassium benzenecarboxylate  Naming: salts of carboxylic acids name of cation + name of acid: drop –ic acid, add –oate CH3CO2Na CH3CH2CH2CO2NH4 (CH3CH2COO)2Mg  Naming: salts of carboxylic acids name of cation + name of acid: drop –ic acid, add –oate CH3CO2Na sodium acetate or sodium ethanoate CH3CH2CH2CO2NH4 ammonium butanoate (CH3CH2COO)2Mg magnesium propanoate  CARBOXYLIC ACID DERIVATIVES: ESTERS Synthesis of esters (ESTERIFICATION) acid + alcohol = ester + water O O R C OH + H O R' R C O R' + H2O Esterification is The reaction of a carboxylic acid and alcohol in the presence of an acid catalyst to produce an ester. O O  H+  CH3—C—OH + H—O—CH2—CH3 CH3—C—O—CH2—CH3 + H2O ethyl acetate (an ester)  Naming Esters The name of an ester contains the names of the alkyl group from the alcohol and the carbon chain from the acid with –ate ending. Name the following compounds. O CH3 O O O O CH3 O Name the following compounds. O CH3 methyl butanoate O O ethyl propanoate O O CH3 methyl 2-methylpropanoate O Draw the following molecules. ethyl ethanoate propyl methanoate ethyl acetate propyl formate methyl benzoate phenyl ethanoate phenyl acetate Draw the following molecules. ethyl ethanoate propyl methanoate ethyl acetate propyl formate methyl benzoate phenyl ethanoate phenyl acetate Write the equation for the following reactions and name the products. A. etanoic acid and ethanol B. propanoic acid and methanol C. benzoic acid and isopropanol Write the equation for the following reactions and name the products. A. etanoic acid and ethanol B. propanoic acid and methanol C. benzoic acid and isopropanol Hydrolysis of esters  Write the products of the hydrolysis of esters. A. Acid hydrolysis of methyl propanoate B. Base hydrolysis of ethyl ethanoate  Write the products of the hydrolysis of esters. A. Acid hydrolysis of methyl propanoate O O H+ CH3 CH2 C OCH3 + H2O CH3 CH2 C OH + CH3OH heat methyl propanoate propanoic acid methanol B. Base hydrolysis of ethyl ethanoate O C2H5O C CH3 + NaOH CH3COO-Na+ + C2H5OH heat ethyl etanoate sodium ethanoate ethanol  Lactone formation Esters in which the ester linkage forms a part of the ring Write the equation for the formation of butyro-lactone. a γ-hydroxy carboxylic acid a γ-lactone  Lactone formation Esters in which the ester linkage forms a part of the ring Write the equation for the formation of butyro-lactone. a γ-hydroxy carboxylic acid a γ-lactone CARBOXYLIC ACID DERIVATIVES: ANHYDRIDES FORMATION OF ANHYDRIDES O O R C R C OH + H2O ANHYDRIDE O OH R C R C O O  Acid Anhydrides Naming Symmetrical anhydrides - replace “acid” with “anhydride” based on the related carboxylic acid Mixed anhydrides— cite the two acids alphabetically. Cyclic anhydrides - Dicarboxylic acids may form anhydrides if a 5- or 6-membered ring is the product - replace “acid” with “anhydride” based on the related dicarboxylic acid IUPAC : ethanoic anhydride benzoic ethanoic anhydride butanedioic anhydride Common: acetic anhydride acetic benzoic anhydride succinic anhydride  ACID ANHYDRIDES Name of the acid(s) anhydride NOMENCLATURE Name the following anhydrides O O O O O H2C C C HC C H3C C H3 C C O O O O O H2 C C C HC C H C H3C C O O O O O  ACID ANHYDRIDES Name of the acid(s) anhydride NOMENCLATURE Name the following anhydrides ethanoic anhydride benzoic anhydride acetic anhydride O O O O O H2C C C HC C H3C C H3 C C O O O O O H2 C C C HC C H C H3C C O O O O O phthaloic anhydride ethanoic methanoic anhydride Write chemical equations for the formation of succinic anhydride (butandioic anhydride). succinic acid Write chemical equations for the formation of succinic anhydride (butandioic anhydride). succinic acid CARBOXYLIC ACID DERIVATIVES: AMIDES O R C Carboxylic acid OH O Amide (functional R C NH2 group in amino acid side chains) N-substituted amide (this type O R C of bound is found in peptides NH R and proteins) O R C R’ N, N-disubstituted amide N R’’  Formation of amides O O R C + NH3 R C + H2O OH NH2 AMIDE AMIDES NOMENCLATURE -oic acid is replaced by –amide suffix ethanoic acid ethanamide acetic acid acetamide Draw the following molecules. methanamide hexanamide formamide benzamide N-methyl-propanamide N-phenyl ethanamide N,N-dimethyl-butanamide N-phenyl acetamide Draw the following molecules. methanamide hexanamide formamide benzamide N-methyl-propanamide N-phenyl ethanamide N,N-dimethyl-butanamide N-phenyl acetamide Draw the structures of the reactants and the products and name (general name) the product for the reaction of a carboxylic acid with a. PCl5 b. elimination of H2O c. R-OH d. NH3 e. NaOH f. elimination of CO2 O O O O PCl5 R C R C R C R C + H2O OH O OH Cl OH R C acyl halide R C O O acid anhydride O O R C + HO R' R C O R' + H2O OH ester O O R C + NH3 R C + H2O OH NH2 RCOOH + NaOH RCOO + Na + H2O R CH2 COOH R CH3 + CO2 alkane Draw and name three different amides with the formula C6H13NO. Draw and name three different amides with the formula C6H13NO. O H hexanamide N H O H 3,3-dimethylbutanamide N H O N N-ethyl-N-methylpropanamide Draw the structure for the reactants and the product for each of the following reactions. A. acyl chloride + primary amine B. Formation of a d-lactam C. Formation of a peptide bond Draw the structure for the reactants and the product for each of the following reactions. A. acyl chloride + primary amine O O R C + H2N R R C + HCl Cl NH-R acyl chloride primary amine N-substituted amide O B. Formation of a d-lactam C CH2 NH R CH CH2 CH2 CH2 COOH -H2O d-Lactam CH2 CH NH2 CH2 R δ-amino acid Five and six membered rings are stable. C. Formation of a peptide bond Comparison of the intermolecular forces of carboxylic acid derivatives Hydogen bond formation H-bonding No H-bonding No H-bonding H-bonding No H-bonding Pair the following structures (A to D) with the boiling points (a to d) a. 222 oC b. 206 oC c. 57 oC d. 165 oC Boiling points: O ESTER CH3 C No H-bonding c. 57 oC O CH3 O AMIDE CH3 C H-bonding a. 222 oC NH2 O N-substituted AMIDE CH3 C b. 206 oC NH CH3 H-bonding O CH3 C CH3 N, N-disubstituted AMIDE d. 165 oC N CH3 No H-bonding  Compare the following compounds with respect to formation of H-bonding. O C H H CH3 N N CH3 O CH3 H H C H C O O O O CH3 C N H > CH3 C O H H O bp = 221° C H bp = 117° CH3 N H Which of the following compounds is more soluble in water? O O CH3 C O CH3 < CH3 C O H More H-bondings (with water), more soluble Draw the structure for the reactants and the product for each of the following reactions. A. acyl chloride + primary amine B. acetic anhydride + methanol Draw the structure for the reactants and the product for each of the following reactions. A. acyl chloride + primary amine O O R C + H2N R R C + HCl Cl NH-R acyl chloride primary amine N-substituted amide B. acetic anhydride + methanol O C O CH3 C + CH3COOH O + HO CH3 CH3 acid CH3 methanol C O CH3 O methyl ethanoate acetic anhydride Ester  Write the structures for the following compounds and give their significance. A. pyruvic acid B. aspirin C. acetoacetate D. 3-hydroxy-butyric acid CH3 C COOH CH2 C COOH A. O OH oxo enol product of glycolysis CH3 C CH2 COOH COOH C. O B. ketone O C CH 3 bodies O CH3 CH CH2 COOH aspirin (acetyl salicylic acid) D. It is used as pain reliever. OH Keto-enol tautomerization of pyruvic acid Reaction in glycolysis: Which of the following statements is false? A. Oxalic acid is a stronger acid than formic acid. B. Acetic acid is a weaker acid than formic acid. C. Unsaturated fatty acid has higher melting point than the corresponding saturated one with the same carbon number. D. Succinic acid forms a cyclic anhydride upon heating. D. Tryacylglycerol consists of glycerol esterified to fatty acids. Which of the following molecules is designated as a ketone body? A. acetyl-CoA B. acetone C. acetophenon D. 2-keto-glutarate E. 2-butanone What is the product of the following reaction? O C ? + CH3OH CH3CH2 Cl A. Methyl ethanoate B. Methyl propanoate C. Ethyl ethanoate D. Ethyl propanoate E. Butanoic acid What is the product of the following reaction? O C + 2 (CH3)2NH ? CH3CH2 Cl A. N-Methylethanamide B. N-Methylpropanamide C. N,N-Dimethylethanamide D. N,N-Dimethylpropanamide E. N-ethyl-N-propylmethanamide What is the general name for the following structure? A. g-lactame B. d-lactone C. lactide D. g-lactone D. lactim