Medical Chemistry Seminar 2024 PDF

Week 10 Seminar Medical Chemistry Seminar 2024 Aldehydes, ketones and quinones Department of Medical Chemistry...

Week 10 Seminar Medical Chemistry Seminar 2024 Aldehydes, ketones and quinones Department of Medical Chemistry UD Faculty of Medicine 1 Key concepts: Electronic structure of carbonyl group IUPAC Nomenclature of aldehydes, ketones and quinones Physical properties Chemical properties Biological significance of aldehydes, ketones and quinones 2 1  Describe the electronic structure of the carbonyl group (hybridization, bond angle, polarization of C-O bond) H C -bond O lone pairs H -bond target for nucleophilic attack H target for electrophilic attack  R C  polar molecule (dipole/dipole interactions) O lone pairs (possible H-acceptor in H-bonding) 3 IUPAC Nomenclature of Aldehydes - Choose the longest continuous carbon chain that contains the carbonyl carbon - Number from the end of the chain closest to the carbonyl carbon (carbon #1!) - Aldehyde ending is -al EXAMPLES aldehyde group is always carbon 1 CH2 CH2 O H 3C CH2 C pentanal H Cl CH3 4 3 CH 1 O 2 CH C 2-chloro-3-methylbutanal CH3 H 4 2  Give systematic and common names for each of the following compounds. (a) Aliphatic aldehydes O O O H C H3C C H3C CH2 C H H H Methanal Ethanal Propanal (formaldehyde) (acetaldehyde) (propionaldehyde) (b) Substituted aliphatic aldehydes H O Cl O Phenylethanal H 5-Chloropentanal (phenylacetaldehyde) (c) Aldehyde group bonded to a ring H O O O H H Benzenecarbaldehyde Cyclohexanecarbaldehyde 2-Naphthalenecarbaldehyde (benzaldehyde) 5 Assign a systematic IUPAC name to each of the following aldehydes and ketones: pentan-3-one 4-ethyl-6-hydroxy-3-methylhexanal 3,3-diethyl-4-methyl- or cyclopentanone diethyl ketone 6 3  Describe (by drawing structures) the interactions - between two aldehyde molecules - between an aldehyde and a water molecule. Dipole-dipole interactions H H  C O  C O H H Hydrogen-bonding H   C O aldehyde-water H H   O H  7 Three main factors to consider when comparing boiling points: 1) what intermolecular forces will be present in the molecules? 2) how do the molecular weights compare? 3) how do the symmetries compare? 8 4  For molecules with a given functional group, boiling point increases with molecular weight The key force that is acting here are Van der Waals dispersion forces, which are proportional to surface area. So as you increase the length of the chain, you also increase the surface area, which means that you increase the ability of individual molecules to attract each other. 9 Role Of Symmetry (or lack thereof) On Boiling Points The more spherelike the molecule, the lower its surface area will be and the fewer intermolecular Van der Waals interactions will operate. Compare the boiling points of pentane (36°C) and 2,2-dimethyl propane (9 °C). The hydroxyl group of 1-pentanol is more “exposed” than it is in 3-pentanol (which is flanked by two bulky alkyl groups), so it will be better able to hydrogen bond with its fellows. 10 5  Write structure for each of the following compounds. Match the compounds (A,B,C) with the boiling points listed (d,e,f) based on intermolecular interactions. A. Acetaldehyde d. 78 oC B. Dimethylether e. 21 oC C. Ethanol f. -25 oC O polar, dipole-dipole e. 21 oC A. Acetaldehyde CH3 C H interactions B. Dimethylether weakly polar, f. -25 oC CH3 O CH3 dipole-dipole interactions polar, H-bonding d. 78 oC C. Ethanol CH3 CH2 OH 11 Complete the following chemical reactions by writing the structure and giving the name for the products. O H CH3 A. [O] Methylbenzene Benzaldehyde B. O O C R + Cl C R - HCl Benzene Acyl chloride Aryl-alkyl ketone O O C. Cl C C + - HCl Benzene Benzoyl chloride Diaryl ketone 12 6  Give the chemical equation and the reaction mechanism for A. Addition of alcohol to an aldehyde B. Formation of acetals A. Addition of alcohol to an aldehyde addition of one mole of alcohol to an aldehyde: nucleophilic addition O H+ O H hemiketal/ hemiacetal R C R' + ROH R C R' O R B. Formation of acetals addition of second mole of alcohol to a hemiacetal followed by elimination (H2O) O H O R H+ R C R' + ROH R C R' + H O O R O R H an acetal 13 Write equations for the reaction of water with the following compounds A. Ethanal B. 2,2,2 trichloroethanal Which reaction will result in a more stable product? Explain. A. Ethanal H H H  H   H C C + H OH H C C OH H O  H OH ethanal NOT STABLE B. 2,2,2 trichloroethanal Cl Cl H  H   Cl C C + H OH Cl C C OH Cl O  Cl OH 2,2,2 trichlorooethanal MORE STABLE „chloral” „chloral-hydrate” 14 7  B. Formation of a Schiff-base O O - H addition H O (1) + (1) C + H2 N- R C N -R C N -R H H TCAI addition product H elimination O (2) C N -R C N + H2 O R H a Schiff-base 15 Formation of a Schiff-base in biochemistry Retinal-Lysine Linkage. Retinal is linked to lysine 296 in opsin by a Schiff-base linkage. In the resting state of rhodopsin, this Schiff base is protonated. 16 8  C. Aldol addition O H O N aOH CH 3 - C-H + CH 2 - C-H Ethanal Ethanal (Acetaldehyde) (Acetaldehyde) O OH   CH 3 - CH- CH 2 -C- H 3-Hydroxybutanal (a -hydroxyaldehyde) Step 1: formation of a resonance-stabilized enolate anion O - HO + H- CH 2 - C-H O O- HO- H + - CH - C-H CH 2 = C- H 2 Enolate anion 17 Step 2: nucleophilic addition of the enolate anion to the carbonyl group of another carbonyl-containing molecule - O O O O - CH 3 - C-H + CH 2 - C-H CH 3 - CH- CH 2 -C- H A tetrahedal carbonyl addition intermediate Step 3: reaction with a proton donor to give the aldol product - O O CH3 - CH- CH 2 -C- H + H- OH OH O CH3 - CH- CH 2 -C- H + OH- 18 9  The Aldol Products: -H2O OH O warm in either O acid or base   CH3 CHCH 2 CH C H 3 C H = C H CH + H 2 O A n  -unsaturated aldehyde Aldol products are very easily dehydrated 19 Give the chemical equation and give the general name of the product for A. reduction of aldehydes B. reduction of ketones C. oxidation of aldehydes D. Oxidation of 1,4 dihydroxybenzene A. Equation for reduction of aldehydes O reduction R C R CH2 OH H aldehyde primary alcohol B. Equation for reduction of ketones D. Oxidation of 1,4 dihydroxybenzene R C R reduction R CH R HO OH O OH 1,4 dihydroxybenzene ketone secondary alcohol oxidation C. Equation for oxidation of aldehydes O O O oxidation O R C R C H OH 1,4 benzoquinone aldehyde carboxylic acid 20 10  How may acetaldehyde be produced in the human body? Biological degradation of ethanol to acetaldehyde and to acetate Step 1 Alcohol O dehydrogenase CH3CH2OH + NAD+ H3C C H + H+ + NADH acetaldehyde toxic Step 2 Acetaldehyde O dehydrogenase H3C C H + NAD+ CH3-COO- + 2H+ + NADH acetate Acetaldehyde (CH3CHO) is produced in living system as an intermediate in the enzymatic oxidation of ethanol, or during the alcoholic fermentation of glucose. People who are sensitive to alcohol suffer from the effect of acetaldehyde accumulated during the biological oxidation of ethanol. Such persons exhibit facial flushing and rapid heart rate (tachycardia) after ingesting even small amounts of alcohol. In the liver, alcohol dehydrogenase converts ethanol into acetaldehyde. Then acetaldehyde, which is the cause of the symptoms when present at high concentrations, is processed to acetate by acetaldehyde dehydrogenase. 21 Draw structures for propanone and 2,4-pentanedione. Show keto-enol tautomerism (isomerization) of these compounds). Which of the two enols is more stable? CH3-C-CH3 CH3-C-CH2 O propanone OH keto enol CH3 C CH2 C CH3 CH3 C CH C CH3 O O OH O keto enol 2,4-pentanedione Why? H Conjugated double bound O O plus H-bound formation with a six-membered ring C C stabilize the enol form CH3 CH CH3 22 11  Draw structures for each of the following compounds and indicate shortly its biological significance (used as a medicine, structural part in biologically important compound etc.). A. chloral hydrate B. diethylether C. acetone D. 2-methyl-1,4-naphtoquinone In slang, a Mickey Finn (or simply a Mickey) is a drink laced A. chloral hydrate: “sleep inducer” with an incapacitating agent, particularly chloral hydrate, given H to someone without their knowledge with the intent to Cl incapacitate them or "knock them out"; hence the colloquial name knockout drops. The "spiking" of drinks is a practice Cl C C OH used by sexual predators at pubs who lace alcoholic Cl drinks with sedative drugs OH B. diethylether: anaesthetic CH3 CH2 O CH2 CH3 C. acetone: one of the “ketone bodies” E. 2-methyl-1,4-naphtoquinone: structural part in vitamin K CH3 C CH3 O O CH3 O 23 Test question #1 Propanone is very soluble in water because A. it is non-polar B. it can form hydrogen bond with water molecules C. water is a polar solvent D. the dipole-dipole interactions are weak between propane and water E. it has two R groups 24 12  Test question #2 Which of the following groups can occur at the end of the chain only? A. Ether B. Alcohol C. Aldehyde D. Ketone E. Thiol 25 Test question #3 What is the correct structure for 2-hydroxyacetophenone: A. B. C. D. E. 26 13  Test question #4 Which of the following molecules is phenylethanal? O O A. B. H H H O C. D. E. C R O O H 27 Test question #5 What is the general name for the product in the following reaction? O O OH O C + H C NaOH C  C C H H3 C H C H H3 C H H2 H2 A. acetal B. imine C. hemiacetal D. ketone E. aldol 28 14  Test question #6 Which of the following mechanisms below is characteristic for the reactions of the carbonyl groups? A. nucleophilic substitution B. nucleophilic addition C. electrophilic addition D. radical substitution E. electrophilic substitution 29 Test question #7 Acetaldehyde when treated with molar excess of ethyl alcohol in the presence of HCl gives A. formaldehyde B. ether C. propanal D. acetal E. aldol 30 15