Pharmaceutical Organic Chemistry (1) PDF

Pharmaceutical Organic Chemistry (1) PHC111 Dr Samar Mowafy  Objectives Introduction to Organic Reactions The reaction equation Reactants (substrates or starting materials) End products Bond Breaking Homolytic Cleavage and Free radicals (Carbon Free Radical,...

Pharmaceutical Organic Chemistry (1) PHC111 Dr Samar Mowafy  Objectives Introduction to Organic Reactions The reaction equation Reactants (substrates or starting materials) End products Bond Breaking Homolytic Cleavage and Free radicals (Carbon Free Radical, Atom or group Free Radical ) Heterolytic Cleavage and formation of ions( Carbocations, Carbanions, Electrophiles, Nucleophiles) Bond Formation and sites of the reaction Types of Chemical Reactions ( Substitution Reactions, Addition Reactions, Elimination Reactions, Rearrangement Reactions, Reaction Mechanism) Principle of organic reaction: In an organic reaction, one organic compound is converted into another. The organic reaction is represented by Reaction Equation as follow: when an organic reaction occurs, some covalent bonds must break and new bonds must form.  Bond Breaking of Reactants Breaking of covalent bonds of reactants gives rise to reaction intermediates. The formed intermediates combine in specific manner according to type of the reaction to give the End products Reaction intermediate is unstable, short-lived species formed during a chemical reaction; examples are Carbon Free Radical, Carbocation or Carbanion.  Types of Bond Breaking (Cleavage): 1] Homolytic Cleavage: Equal breaking of the covalent bond to give Free Radicals Free radical: is a neutral species with a carbon that has only three bonds (6 electrons) and 7 outer-shell electrons, one of which is unpaired or odd 2] Heterolytic Cleavage It is Unequal breaking of the covalent bonds, to produce Ions.  What is Carbanion? A species with a carbon that has only three bonds, eight outer-shell electrons including one nonbonding pair, and a negative charge. What is Carbocation? A species with a carbon that has only three bonds, and a positive charge.  What is Electrophile? An electron deficient species that accepts electrons form nucleophiles in a chemical reaction. Electrophile may be with or without positive charge. E or E+. Electrophiles with positive charge: Cl+ Br+ H+ H3O+ R-CH2+ R2CH+ R3C + NO+ NO2+ HSO3 + Electrophiles without positive charge but having electron deficient atom  What is Nucleophile? A species with electron availability (electron rich) that donates electrons to electrophiles in a chemical reaction. A nucleophile may be with or without negative charge. :Nu- or :Nu Nucleophiles with negative charge: Cl:- Br:- H- R-CH2: - R2CH:- R3C:- :NO3- HO:- Nucleophiles without negative charge but having atom with lone pair Test Yourself: Classify the following as Free radical, electrophile or nucleophile:  Bond Formation and reaction site: Bond formation takes place between the reaction intermediate (carbon free radical, carbocation, or carbanion) and the active part of the reagent (free radical, electrophile, or nucleophile). In organic reaction, reaction occurs on CARBON. - A carbon free radical is attacked by free radical. - A carbocation is attacked by nucleophile. - A carbanion is attacked by electrophile.  Test Yourself: Complete the following chemical equations: Description of Carbon as primary (1o ), secondary (2o ), tertiary (3o ) or quaternary (4o ): for radical, a carbon may be described as (1o ), (2o ), or (3o ). 1 o carbon: carbon attached to one carbon. 2 o carbon: carbon attached to two carbons. 3 o carbon: carbon attached to three carbons. 4 o carbon: carbon attached to four carbons.  Test Yourself: Draw: methyl free radical, 1o free radical, 2o free radical, 3o free radical. Draw: methyl carbocation, 1o carbocation, 2o carbocation, 3 o carbocation. Draw: methyl carbanion, 1o carbanion, 2o carbanion, 3o carbanion Types of Chemical reaction: The type of the reaction is determined by the type of carbon (free radical, carbocation, or carbanion) in which reagent is going to attack. 1] Substitution reaction: In substitution reaction, the leaving and entering group is of the same type. A) Free Radical Substitution Reaction: Free radical replaces free radical. B) Nucleophilic Substitution Reaction: Nucleophile replaces nucleophile. Occurs in alkyl halides, alcohols, carboxylic acids, amines C) Electrophilic Substitution Reaction: Electrophile replaces electrophile. (In aromatic compounds) 2] Addition reactions: Addition reactions take place on Pi bond. By addition reactions occurs formation of saturated compounds at expense of unsaturated compounds. A) Electrophilic Addition Reactions: This type of reactions occurs in alkenes and alkynes. H + (electrophile) is added first to C = C. B) Free Radical Addition Reactions: Ex: Addition of H-Br to alkene in presence of peroxide as catalyst. C) Nucleophilic Addition Reactions: Examples are addition to C = O of aldehydes or ketones. CN- (nucleophile) is added first to C = O 3] Elimination reactions: In this type of reactions occurs formation of unsaturated compounds at the expense of saturated compounds. Examples: Formation of alkenes from alcohols or alky halides 3] Elimination reactions: 4] Rearrangement reactions: In this occasion, the best example to be mentioned is the addition of water to acetylene in presence of H2SO4 and HgSO4 (mercuric sulphate).  Reaction mechanism: It is a step by step (stepwise) description of how a chemical reaction occurs. If the reaction takes place in more than one step, the slowest step is the rate determining step (will be discussed later) Test Yourself Complete the following chemical equations then identify type of the reaction.