Medical Chemistry Seminar 2024 PDF

Week 9 Seminar 1-2 Medical Chemistry Seminar 2024 Organic Halogen Compounds, Alcohols, Phenols and Ethers, Organic Sulfur Compounds Department of Medical Chemistry UD Faculty of Medicin...

Week 9 Seminar 1-2 Medical Chemistry Seminar 2024 Organic Halogen Compounds, Alcohols, Phenols and Ethers, Organic Sulfur Compounds Department of Medical Chemistry UD Faculty of Medicine  Functional groups in organic compounds Compound Functional Group Compound Name Name R X halogen Halide R OH hydroxyl Alcohol Ar OH hydroxyl Phenol R O R alkoxy Ether R - SH thiol Thioalcohol R – NH2 amino Amine R C O aldehyde (or formyl) Aldehyde H carbonyl (keto or oxo) Ketone R2C O carboxyl Carboxylic Acid R C O OH  Alkyl and Aryl Halides, RXa CH3Br CH3CHCH2 methyl bromide (bromomethane) Br Br b.p. 5 oC propylene dibromide (1,2-dibromopropane) CH3I methyl iodide b.p. 141 oC (iodomethane) CH2 CHCl b.p. 42 oC vinyl chloride (chloroethene) CH3CH2Br ethyl bromide b.p. 14 oC (bromoethane) b.p. 38 oC Cl CH3CH2CH2Br propyl bromide chlorobenzene (1-bromopropane) oC b.p. 132 oC b.p. 71 a Common name (systematic name)  Nomenclature I. for haloalkenes, numbering is determined by the location of the C-C double bond CH3 3 Br 4 3 2 1 4 2 CH3 CCH= CH 2 1 5 Cl 6 3-Chloro-3- 4-Bromo- methyl-1-butene cyclohexene  Nomenclature II. several polyhaloalkanes are common solvents and are generally referred to by their common or trivial names CH 2 Cl 2 CHCl 3 Dichloromethane Trichloromethane (Methylene chloride) (Chloroform) CH 3 CCl 3 CCl 2 =CHCl 1,1,1-Trichloroethane Trichloroethylene (Methyl chloroform) (Trichlor)  Give the name of the following organic halogen compounds. CH3 CH2 Cl CH3 CH CH3 Cl 1-chloroethane (ethyl chloride) 2-chloropropane (isopropyl chloride) CH2 CH Cl Cl 1-chloroethene (vinyl chloride) chlorobenzene Draw the structure for each of the following compounds. 1 2 3 4 5 3-chloropentane C C C C C Cl CH 2 Cl benzyl chloride 6 5 4 3 2 1 5-fluoro-1-hexanol CH3 CH CH2 CH2 CH2 CH2 OH F Write the chemical equation for the reaction of methyl chloride witht he following compounds. What are the names of the products? What is the general reaction mechanism? 1. Sodium hydroxide CH3 Cl + NaOH CH3OH + NaCl methanol 2. Ammonia CH3 Cl + NH3 CH3 NH2 + HCl methylamine 3. Hydrogensulfide ion CH3-Cl + SH- CH3-SH + Cl- methanethiol General reaction mechanism: Nucleophilic Substitution SN  Give the name of the organic compounds that can be produced from alkyl halides by substitution. Nu - + CH 3 Br CH 3 Nu + Br - - HO CH 3 OH alcohol - RO CH 3 OR ether - HS CH 3 SH thiol - thioether RS CH 3 SR + NH3 CH 3 NH 3 alkylammonium ion Alkyl halides are the starting materials for organic synthesis. Write the chemical reaction of 2-chloro-2-methylbutane with cc. sodium hydroxide and give the name of the two possible products. 2-methyl-2-buten 2-methyl-1-buten What is the reaction mechanism? Elimination Which one is the main product? 2-methyl-2-buten Significance of organic halogen compounds Fill in the missing words in the following sentences. ………………………….and …………………are two important iodine containing hormones. Triiodothyronine (T3) and thyroxine (T4) …………….. is an organic solvent that was once used as an inhalational anesthetic. Chloroform (CHCI3) ………………………….. has been used as a local anesthetic. Chloroethane (CH3CH2Cl) ………………….is an antiseptic that is frequently used to treat minor skin conditions. Iodoform (CHI3 ) Test Questions What is the typical chemical reaction of alkyl halides? A. nucleophilic substitution B. radical addition C. electrophilic addition D. radical substitution E. nucleophilic addition A What is the product of the reaction between ethyl chloride and hydrogen sulfide? A. ethyl sulfide B. ethanethiol C. ethylamine D. ethanol E. acetic acid B  Alcohols, ROHa CH3OH HOCH2CH2OH methyl alcohol ethylene glycol (methanol) (1,2-ethanediol) b.p. 65 oC b.p. 197 oC CH3CH2OH CH2CHCH2 ethyl alcohol (ethanol) OH OHOH b.p. 78 oC glycerol or glycerin CH3CH2CH2OH (1,2,3-propanetriol) propyl alcohol b.p. 290 oC (dec) (1-propanol) b.p. 97 oC 2 1 CH3CHCH3 CH2CH2OH OH isopropyl alcohol (2-phenylethanol) (2-propanol) b.p. 219 oC b.p. 82 oC a Common name (systematic name)  NOMENCLATURE OF ALCOHOLS 1. Select the longest continuous carbon chain to which the hydroxyl is directly attached. Change the name of the alkane corresponding to this chain by dropping the final e and adding the suffix ol. 2. Number the longest continuous carbon chain so as to give the carbon atom bearing the hydroxyl group the lower number. Indicate the position of the hydroxyl group by using this number. Indicate the position of order substituents (as prefix) by using the numbers corresponding to their positions along the carbon chain. Cl 3CH 2CH 1CH OH 4CH 3CH 2CH 1CH OH 2 2 2 3 2 2 CH3 3-chloro-1-propanol 3-methyl-1-butanol 5CH 4CH 3CH 2CH 1CH OH 1CH 2CH 3CH 4CH 5CH 3 2 2 3 2 2 Cl CH3 OH 4-chloro-2- methyl-1-pentanol 4-penten-2-ol  Phenols, ArOHa OH OH OH phenol a-naphtol OH m.p. 42 oC oC m.p. 94 OH hydroquinone m.p. 169 oC OH OH CH 3 p-cresol catechol m.p. 36 oC m.p. 104 oC a These phenols are known best by their common names as given above. Phenol is also known as „carbolic acid.” Most phenols, unlike the lower molecular mass alcohols, are solids at room temperature.  NOMENCLATURE OF PHENOLS OH OH OH OH CH 3 CH 3 phenol o-cresol m-cresol CH 3 (benzenol) (2-methylbenzenol) OH (3-methylbenzenol) OH p-cresol OH (4-methylbenzenol) OH OH resorcinol catechol OH (1,3-benzenediol) (1,2-benzenediol) OH hydroquinone OH (1,4-benzenediol) OH OH HO OH OH HO OH pyrogallol hydroxyhydroquinone phloroglucinol (1,2,3-benzenetriol) (1,2,4-benzenetriol) (1,3,5-benzenetriol) Draw the structure for each of the following compounds. All possible isomers for methylphenol (cresol) OH OH OH C H3 C H3 o-cresol C H3 m-cresol 2-phenylethanol p-cresol CH 2 CH 2 OH 1,4-butanediol CH2 CH2 CH2 CH2 OH OH Write formulas to illustrate the structure of the following compounds. (a) Primary alcohol R CH2 OH (b) Secondary alcohol R CH R OH R (c) Tertiary alcohol R C OH OH R OH (d) Naphthol or a  (e) Enol R HC CH OH R HC CH2 (f) Diol OH OH How can hydrogen-bonding form with the following molecules? o – fluorophenol F H O Intramolecular hydrogen-bonding (normal boiling point) p - fluorophenol H O F H O F Intermolecular hydrogen-bonding (higher boiling point) Choose the molecules that are able to form hydrogen- bonding. Which molecules can form intramolecular and intermolecular hydrogen-bonding? A. O CH3 No H-bonding H O O OH C O H B. C Intramolecular H O H O N O H O N C. O2N OH O O Intermolecular D. CH3 SH No H-bonding Compare the boiling points of the following compounds and explain the differences in the intermolecular interactions. A. CH3 OH Mr = 32 B. CH3 O CH3 Mr = 46 C. H2O Mr = 18 D. CH3 SH Mr = 48 C > A > B, D  EXPLANATION A. O O C. O O CH3 H H CH3 H H H H..O....O.. CH3 H H H.. O O O CH3 H H H H H 3 molecules of methanol 4 molecules of H2O are „coordinated” are „coordinated”..O.. D..... B. S CH3 CH3 CH3 H polar (but no H-bonding) polar (but no H-bonding) Draw the structure and list the following alcohols in order of their increasing solubility in water. Explain the different solubilities. A, 2,2 - dimethyl - 1- butanol CH3 CH3 CH2 C CH2 OH CH3 hydrophobic chain is shorter, shape is more spherical B, ethanol CH3 CH2 OH hydrophobic chain is shortest C, 1 - hexanol CH3 CH2 CH2 CH2 CH2 CH2 OH hydrophobic chain is longest hydrophilic and able to form H-bonding C < A < B The longer is the hydrophobic alkyl chain, the lower is water solubility. Test Questions Which of the following compounds is NOT an alcohol? A. ethanol B. 2-propanol C. ethylene glycol D. cathecol E. glycerol D The boiling point of 1-butanol is less than the boiling point of ethylene glycol (1,2-ethanediol) because A. 1-butanol has higher molecular mass. B. ethylene glycol has smaller size. C. 1-butanol is a nonpolar molecule. D. hydrogen bonds are NOT formed in ethylene glycol. E. more hydrogen bonds are formed in ethylene glycol then in 1-butanol. E Test Questions Which compound has the highest solubility in water? A. methanol B. carbon tetrachloride C. hexane D. benzene E. methane A Write chemical reactions to illustrate how alcohols could be generated from the following compounds. Classify the alcohol produced in the reaction. Classify the type of reaction mechanism. 1. ethene +? ? H+ CH2 CH2 + H2O CH3 CH2 OH electrophilic addition primary alchol 2. propene +? ? H+ CH3 CH CH2 + HOH CH3 CH CH3 OH electrophilic addition secondary alcohol Write chemical reactions to illustrate how alcohols could be generated from the following compounds. Classify the alcohol produced in the reaction. Classify the type of reaction mechanism. 3. aldehyde +? ? O R C + H2 R CH2 OH H primary alcohol catalytic hydrogenation (addition) 4. ketone +? ? R C R + H2 R CH R O OH catalytic hydrogenation secondary alcohol (addition) Write chemical reactions to illustrate how alcohols or phenols could be generated from the following compounds. Classify the alcohol produced in the reaction. Classify the type of reaction mechanism. 5. alkyl halide + ? ? R CH2 Cl + KOH R CH2 OH + KCl nucleophilic substitution primary alcohol 6. aryl-halide + ? ? nucleophilic substitution phenol Acidity of alcohols and phenols Alcohols CH3 OH CH3 O- + H + CH3 C H2 OH < O < Cl CH2 OH CH3 H Delocalized electron (more stable) Phenols OH + H+ O Phenols are stronger acids than alcohols OH CH3 OH F F OH < < F Electron donor groups Electron acceptor groups decrease acidity increase acidity Draw the structure for the following molecules and compare their acidity. cyclopentanol OH O- Negative charge localizes to oxygen + H+ n-butanol Negative charge localizes to oxygen CH3 CH2 CH2 CH2 OH CH3 CH2 CH2 CH2 O- + H+ Very weak acids: cyclopentanol  butanol Draw the structure for the following molecules and compare their acidity. phenol OH O- Negative charge delocalizes to + H+ the rings p-fluorophenol OH O- + H+ Electronegative F helps delocalization F F Weak acids: phenol < p-fluorophenol Draw the structure for each of the following molecules. OH CH3 A. o-cresol (o-methylphenol) B. water H O H C. methanol CH 3 OH OH F F D. 2,4,6 - trifluorophenol F E. 2 - chloroethanol Cl CH2 CH2 OH OH F. phenol List the compounds in order of their increasing acidity. C = B < E Ethers CH3OH 65o CH3CH2OH 78o (CH 3)2O -25o CH3CH2CH2OH 97o CH3OCH 2CH3 8o (CH3)2CHOH 82o CH3CH2CH2CH2OH 118o CH3OCH 2CH2CH3 39o CH3CH2CHOHCH 3 99o CH3OCH(CH 3)2 32o (CH3)2CHCH2OH 107o (C2H5)2O 35o (CH 3)3COH 83o Hydrogen-bridge formation No hydrogen bonding Test Questions Which of the following molecules is an epoxide? A B C O CH2-CH2 D CH3-CH2-O-CH2-CH3 E R-O-CH2-CH2-O-O-CH2-CH2-O-R C Which one was once used as an inhalational anesthetic? D Which of the above molecules is a peroxide? E Which of the above molecules is highly reactive? C and E Important sulphur containing organic compounds  Draw the structures for the following sulphur containing molecules A. etanethiol B. dimethyl sulfide C. methanesulfinic acid CH3-CH2-SH CH3-S-CH3 CH3-S-OH O D. methanesulfonic acid E. dimethyl sulfoxide F. dimethylsulfone O O CH3-S-CH3 CH3-S-OH CH3-S-CH3 O O O G. 2-mercaptoethanol HO-CH2-CH2-SH  Properties of thiols and thioethers Fill in the missing spaces in the table Thiols are analogs of Thioethers are analogs alcohols of ethers Polarity of the S-H bond is O-C bond is S-C bond functional O-H bond is polar slightly polar slightly polar is nonpolar group Hydrogen No Yes No No bonding Boiling points Relatively high Lower than that of Nearly the same as for similar alcohols similar alkanes Acidity Extremely Stronger acids NA NA weak acids than alcohols Write chemical equations and give the name of the products. Mild oxidation of thiols oxidáció 2 R S H redukció R S S R disulfide Vigorous oxidation of thiols O oxidáció R S H R S OH sulfonic acid O Reaction of thiols with alkyl halides R-SH + RCl R-S-R + HCl thioether Oxidation of sulfide in two steps O O enyhe oxidáció erélyes oxidáció R S R' R S R' R S R' sulfone O sulfoxide  What is the name of the following compounds? Identify the most important functional group in the molecules What is their biological function? L-cysteine L-methionine thiol sulfide Protein structure Protein structure Enzyme activity Methyl-group transfer Reaction with heavy metal ions Coenzyme-A (CoA) thiol Transfer of active acetate Write chemical equations for the following reactions A. Mild oxidation of 2-mercaptoethanol HO-CH2-CH2-S disulfide oxidation 2 HO-CH2-CH2-SH S-CH2-CH2-OH B. Formation of disulfide between two Cys amino acids - - COO- mild oxidation COO COO 2 H2N CH H2N CH H2N CH CH2 SH CH2 S S CH2 Cys-SH Cys-S-S-Cys disulfide Test Questions Classify the following compound as CH3-S-CH3 O A. Thiol B. Sulfoxide C. Sulfone D. Sulfide E. Disulfide B The mild oxidation of a thiol produces A. Thioaldehyde B. Thioketone C. Sulfide D. Disulfide E. Persulfide D