Pharmaceutical Organic Chemistry Lecture Notes PDF

Pharmaceutical Organic Chemistry  Pharmaceutical Organic Chemistry I (PC102) By: Asst. Prof. Abeer Abdelazeem Hello Dr. Hany Gamal 2  Lecture 2 Course Learning Outcomes (CLOs)...

Pharmaceutical Organic Chemistry  Pharmaceutical Organic Chemistry I (PC102) By: Asst. Prof. Abeer Abdelazeem Hello Dr. Hany Gamal 2  Lecture 2 Course Learning Outcomes (CLOs) 1-1-1-1. Define the basics of the chemistry of aliphatic hydrocarbons. 1-1-1-1. Recall the mechanisms of reactions of aliphatic hydrocarbons. (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 3  Hydrocarbons ❖ Hydrocarbons are compounds that only contain carbon and hydrogen atoms, and they can be classified as follows depending on the bond types present within the molecules. (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 4  Hydrocarbons Chemical structures presentation (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 5  Alkanes ❖ Hydrocarbons having single bonds (saturated) are classified as alkanes. ❖ The carbon atoms of the molecule are arranged in chains (alkanes) or in rings (cycloalkanes). ❖ All alkanes have the general molecular formula CnH2n+2 and are called saturated hydrocarbons. (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 6  Alkanes Nomenclature of Alkanes 1- IUPAC Nomenclature It is a systematic method of naming organic chemical compounds as recommended by the International Union of Pure and Applied Chemistry (IUPAC). (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 7  Alkanes Nomenclature of Alkanes 1- IUPAC Nomenclature 1- Select the parent function group (the highest priority). 2- Choose the longest chain containing the parent function group. 3- Write the basic name: Prefix (no. of carbon) + Suffix (ane) 4- Numbering by giving the substitution/s the lowest possible number. 5- Write the substituent with ALPHABTICAL considerations. (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 8  Alkanes Nomenclature of Alkanes 1- IUPAC Nomenclature If two equal chains.. Select the one with more substitution If Cycle vs Open alkanes.. Longest Chain (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 9  Alkanes Nomenclature of Alkanes 1- IUPAC Nomenclature If two equal chains.. Select the one with more substitution If Cycle vs Open alkanes.. Longest Chain (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 10  Alkanes Nomenclature of Alkanes 1- IUPAC Nomenclature 1 CH 7 CH3 3 2 CH2 6 CH2 H H CH3 CH C CH2 CH3 CH3 CH C CH2 CH3 3 4 5 4 ✓ Give substituent the lowest number or sum CH2 CH2 CH3 CH2 CH2 CH3 ✓ If equivalent positions.. lower number is given to 5 6 7 3 2 1 branch pts. at carbons 3 and 4 branch pts. at carbons 4 and 5 substituent of lower alphabetical order. 1 9 8 2 CH3 CH2 H3C CH2 CH3 CH3 CH2 H3C CH2 CH3 CH3 CH CH2 CH2 CH CH CH2 CH3 CH3 CH CH2 CH2 CH CH CH2 CH3 9 7 6 5 4 3 2 1 3 4 5 6 7 8 branch pts. at carbons 3, 6, 7 branch pts. at carbons 3,4,7 (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 11  Alkanes Nomenclature of Alkanes 1- IUPAC Nomenclature ✓ Do not forget the position and number of Substitutions ✓ (di-, tri-, tetra-, etc.) are ignored in alphabetizing. ✓ (iso, neo and cyclo) are not ignored in alphabetizing. (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 12  Alkanes Nomenclature of Alkanes 1- IUPAC Nomenclature H3C H3C CH3 Parent CH Parent Parent CH H3C CH CH2Chain Parent Chain Chain H3C C Chain H3C CH2 H3C CH 3 CH3 sec-butyl- Isopropyl- Isobutyl- tert-butyl- (1-methylpropyl) (1-methylethyl) (2-methylpropyl) (1,1-dimethylethyl) H3C CH Parent Parent Chain H3C CH CH2 Chain H3C CH2 CH3 sec-butyl- Isobutyl- (1-methylpropyl) (2-methylpropyl) (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 13  Alkanes Nomenclature of Alkanes 1- IUPAC Nomenclature 1 2 3 4 5 6 7 (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 14  Alkanes Nomenclature of Alkanes 2- Common Names (Trivial Names) (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 15  Alkanes Nomenclature of Cycloalkanes ❖ Cycloalkanes are alkanes that are cyclic with the general formula CnH2n. ❖ The nomenclature of cycloalkanes is almost the same as that of alkanes, with the exception that the prefix cyclo- is to be added to the name of the alkane. (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 16  Alkanes Physical Characters of alkanes ✓ Alkanes have similar chemical properties, but their physical properties vary with molecular weight and the shape of the molecule. ✓ Compared with other functional groups, alkanes have low boiling points. Heptane bp 98°C Nonane Van der Waals forces bp 150°C Induced dipole-Induced dipole Interaction (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 17  Alkanes Preparation of Alkanes Alkenes Reduction Ketones Same C. Number R-X ALKANES Wurtz Involving Metals More C. Number Corey H Decarboxylation Soda lime (PC102) Less C. Number Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 18  Alkanes Preparation of Alkanes Reduction Alkenes of Alkenes Reduction Ketones - Catalytic hydrogenation of unsaturated hydrocarbon Same C. Number R-X ALKANES Wuertz Involving Metals More C. Number Corey H Decarboxylation Soda lime (PC102) Less C. Number Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 19  Alkanes Preparation of Alkanes Alkenes Reduction Reduction Ketones of Ketones Same C. Number R-X - Involve the conversion of carbonyl gp. to methylene gp. ALKANES Wuertz Involving Metals More C. Number Corey H Decarboxylation Soda lime (PC102) Less C. Number Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 20  Alkanes Preparation of Alkanes Alkenes Reduction Ketones Same C. Number Reduction R-X of Alkyl halides ALKANES Wurtz Involving Metals More C. Number Corey H Decarboxylation Soda lime (PC102) Less C. Number Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 21  Alkanes Preparation of Alkanes Alkenes Reduction Ketones Same C. Number Double number of carbons R-X (Symmetrical alkane synthesis) ALKANES Wurtz Wuertzreaction Na or Zn Involving Metals More C. Number Corey H Decarboxylation Soda lime (PC102) Less C. Number Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 22  Alkanes Preparation of Alkanes Alkenes ❖ Limitations of Wurtz reaction : 1- Methane can not be obtained by this method. Reduction Ketones 2- The reaction fails in the case of tertiary halides. Same C. Number 3- Mixed alkyl halides give a mixture of alkanes which R-X are difficult to separate. ether R X + R' X solvent R R + R' R' + R R' ALKANES Wurtz Wuertzreaction Involving Metals Corey H Double number of carbons More C. Number (Symmetrical alkane synthesis) Decarboxylation Soda lime (PC102) Less C. Number Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 23  Alkanes Preparation of Alkanes Alkenes Reduction Ketones 1st RX Same C. Number R-X 2nd RX ALKANES Wuertz Involving Metals More C. Number Corey house synthesis Corey H Increase number of carbons Decarboxylation Soda lime (Unsymmetrical alkane synthesis) (PC102) Less C. Number Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 24  Alkanes Preparation of Alkanes Alkenes Reduction Ketones Same C. Number R-X ALKANES Wuertz Involving Metals More C. Number Corey H Decarboxylation Decarboxylation Soda lime by soda Lime (PC102) Less C. Number Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 25  Alkanes Preparation of Cycloalkanes Internal Wurtz reaction Reduction of Alkenes, Ketones (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 26  Alkanes Electron Displacement Exerted by Substituents (G): Due to the difference in EN between C & G atoms & characterized by; Electron displacement along the chains via  bond & undergoes permanent polarization in the molecules. The effect decreases with the increase in distance from substituent. Two types; -I effect & +I effect. (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 27  Alkanes Reactions of Alkanes ❖ Alkanes contain only strong σ bonds, and all the bonds (C_C and C_H) are nonpolar. As a result, alkanes are quite unreactive towards most reagents. 1- Combustion or oxidation of alkanes: Alkanes undergo combustion reaction with oxygen at high temperatures to produce carbon dioxide and water. This is why alkanes are good fuels. % of unbranched alkanes (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 28  Alkanes Reactions of Alkanes ❖ Alkanes contain only strong σ bonds, and all the bonds (C_C and C_H) are nonpolar. As a result, alkanes are quite unreactive towards most reagents. 2- Free radical substitution reactions (Halogenations): - Radical reactions are often called chain reactions. - All chain reactions have three steps: chain initiation, chain propagation and chain termination. To maximize the formation of monohalogenated product, a radical substitution reaction must be carried out in the presence of excess alkane. (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 29 A) Carbocations: positively charged species (+ve) containing a carbon atom having only 6 electrons in 3 covalent bonds. ✓ Carbocation carbon is sp2 hybridized C and its shape is planar. 120 + ✓ +I effect of R groups stabilizes the carbocations. Order of stability of carbocations B) Carbanions: negatively charged species (-ve) containing carbon atom with 3 bonds and unshared pairs of electrons. ✓ Carbanion carbon is sp3 hybridized C and its shape is tetrahedral. ✓ +I effect of the R group destabilizes the carbanion. Order of stability of carboanions (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 30  C) Free radicals: They are electrically Neutral-High energy species with one odd electron. Order of stability of free radicals The same as that of carbocations. Types of carbons (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 31  Alkanes Reactions of Alkanes ❖ Alkanes contain only strong σ bonds, and all the bonds (C_C and C_H) are nonpolar. As a result, alkanes are quite unreactive towards most reagents. 2- Free radical substitution reactions (Halogenations): Mechanism: (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 32  Alkanes Reactions of Alkanes ❖ Alkanes contain only strong σ bonds, and all the bonds (C_C and C_H) are nonpolar. As a result, alkanes are quite unreactive towards most reagents. 2- Free radical substitution reactions (Halogenations): Chloride radical is much more reactive than the bromide radical. Thus, the bromide radical is much more selective than the chloride radical. (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 33  Alkanes Reactions of Alkanes ❖ Alkanes contain only strong σ bonds, and all the bonds (C_C and C_H) are nonpolar. As a result, alkanes are quite unreactive towards most reagents. 2- Free radical substitution reactions (Halogenations): (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 34  Alkanes Reactions of Cycloalkanes Baeyer Strain theory Reactive Stable (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 35  Alkanes Reactions of Cycloalkanes (PC102) Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 36 Ass. Prof. Abeer Abdelazeem Mohamed, Dr. Hany Gamal 37 38