Pharmaceutical Organic Chemistry-1 PC102 Lec.5 PDF

Pharmaceutical Organic Chemistry-1 PC102- Lec.5 Dr Samar Samir Tawfik [email protected] Dr Selwan Mahmoud [email protected]  Conformational isomerism Produced by rotation (twisting) about σ bonds, and are often rapidly interconverting at room...

Pharmaceutical Organic Chemistry-1 PC102- Lec.5 Dr Samar Samir Tawfik [email protected] Dr Selwan Mahmoud [email protected]  Conformational isomerism Produced by rotation (twisting) about σ bonds, and are often rapidly interconverting at room temperature. Also named conformers, rotamers or rotational isomers. Study of energy change due to free rotation is called Conformational analysis. The best way to represent them is using Newman Projection.  Conformational analysis of ethane: Ethane has two conformations, staggered and eclipsed. In staggered conformation, each C-H bond of one carbon bisects an H-CH angle of the other carbon. In eclipsed conformation, each C-H bond of one carbon is aligned with a C-H bond of the other carbon. In drawing the Newman projection formulas for ethane, C-1 which is close to the eye becomes (middle point) and the C-2 becomes circle in the back of the middle point) The eclipsed conformation (high energy) is unstable, because of steric repulsion between the H-atoms converts into the more stable staggered form by 60o rotation. There is enough heat available at room temperature for rapid conversion. The staggered conformation is much preferred; at any time, almost all ethane molecules have the staggered arrangement. Torsional strain occurs when the angle between adjacent bonds is other than 60₀.  Conformational analysis of Butane: Considering the rotation between the two middle carbons, butane has 2 different staggered conformations. Gauche and anti conformations. Types of strain: Conformation of Cycloalkanes with Small rings: Cyclobutane conformation Cyclopentane conformation  Conformation of Cyclohexane:  Six membered rings are non-planar.  The most stable conformation for cyclohexane is the chair conformation, with C-C-C bond angle 111₀ with no tortional and no angle strain.  The boat conformation is less stable than chair form. It has no angle strain but it has eclipsing strain from the pairs of hydrogen on C-1-C4, C2- C3 & C5- C6 carbons.  The twist-boat form is more stable than the boat form.  The half chair conformation is the least stable conformation of cyclohexane because of both angle and eclipsing strain.  Chair > twist boat > boat > half chair “according to stability”  Axial and equatorial bonds of cyclohexane: The 12 hydrogen atoms of cyclohexane can be divided into 2 groups:  Synthesis of Alkanes: 1) Clemmenson reduction of carbonyl compounds: Zinc amulgum 2) Catalytic hydrogenation of alkenes and alkynes: syn-addition: addition of hydrogen from the same side. Shaking an alkene (or alkyne) under hydrogen at room temperature and at atmospheric pressure in presence of a transition metal catalyst as platinum or palladium. If nickel is used, reaction takes place at 200℃.  3) Coupling reaction (Wurtz reaction): Two molecules of alkyl halide couple together in presence of sodium metal. 4) Decarboxylation of carboxylic acids with soda lime:  Reactions of Alkanes and cycloalkanes: Alkanes are non-reactive compounds due to the strong σ-bonds. 1) Combustion (Oxidation): Produces carbon dioxide and water. 2) Halogenation: Replacement of hydrogen by halogen through free radical substitution reaction. Free radicals are atoms or groups of atoms which have a single unpaired electron. Free radicals are formed if a bond splits evenly, each atom gets one of the two electrons. Reaction between methane and chlorine: In presence of ultraviolet light (sunlight). This is a photochemical reaction – a reaction brought about by light. Also can be done by heating at high temperature. This reaction is a chain reaction involving 3 steps: Multiple substitutions in methane/ Chlorine reaction: Chloromethane, dichloromethane, trichloromethane or tetrachloromethane may be produced. If you use enough chlorine you will eventually get CCl4,