PHR 301: MEDICINAL CHEMISTRY 1 Lecture 3

C=C Double Bond (sp2 hybridized orbitals)

Addition Reactions Electrophilic addition to double bonds Free radical addition to double bonds Nucleophilic addition to carbonyl group

Addition to Double Bonds Electrophilic addition to double bond in alkenes Symmentrical alkenes Unsymmetrical alkenes Markovnikov’s rule Dienes 1,2 addition 1,4 addition Free-radical addition Applications

Spring 2016, PHR 301: Medicinal Chemistry 1 Problem Set 1 Instructor: Dr. M. Zulfiquer Hossain Assigned: Due: Consider the reaction: H 2 O + HCl ⇋ H 3 O + + Cl - a)Draw the Lewis structure for each reactant and product. Identify the electrophilic atom(s). b)Sketch the reaction mechanism for this reaction. Include any intermediate(s) that might form. c)Does H 2 O act as a Lewis acid or Lewis base in this reaction? Why? d)Does H 2 O get oxidized or reduced in this reaction? Why? e)Draw an energy diagram for this reaction. f)Where does the activation energy for this reaction come from? g)What was the most difficult part of this problem? Why did you find it difficult?

Let’s fill in the blanks: semester-long group activity (Not to be confused with the term project)

Major Functional Groups (Organic Chemistry. Carey. 8 th Edition) ExampleCharacteristic Reaction TypeExampleApplication Hydrocarbons AlkanesFree-radical substitution AlkenesElectrophilic addition to double bond Unsymmetrical alkenesElectrophilic addition to double bond, free-radical addition AlkynesElectrophilic addition to triple bond DienesElectrophilic addition to double bonds (1,2 and 1,4 addition) ArenesElectrophilic aromatic substitution Hydrocarbon derivatives Alkyl halidesNucleophilic substitution, elimination Alenyl halidesElectrophilic addition to double bond, elimination Aryl halidesElectrophilic/nucleophilic aromatic substitution Oxygen-containing organic compounds AlcoholsDehydration, conversion to alkyl halides, esterification PhenolsElectrophilic aromatic substitution EthersCleavage by hydrogen halides EpoxidesNucleophilic ring opening AldehydesNucleophilic addition to carbonyl group KetonesNucleophilic addition to carbonyl group

Major Functional Groups (Organic Chemistry. Carey. 8 th Edition) ExampleCharacteristic Reaction TypeExampleApplication Carboxylic acids and derivatives Carboxylic acidsIonization of carboxyl; esterification Acyl halidesNucleophilic acyl substitution Acid anhydridesNucleophilic acyl substitution EstersNucleophilic acyl substitution AmidesNucleophilic acyl substitution Nitrogen-containing organic compounds AminesNitrogen acts as a nucleophile NitrilesNucleophilic addition to carbon-nitrogen triple bond Nitro compoundsReduction of nitro group to amine Sulphure-containing organic compounds ThiolsOxidation to a sulfenic, sulfinic, or sulfonic acid or to a disulfide SulfidesAlkylation to a sulfonium salt, oxidation to a sulfoxide or sulfone