Fundamentals of Medicinal and Pharmaceutical Chemistry PDF

Fundamentals of Medicinal and Pharmaceutical Chemistry FUNCHEM.11 Introduction to organic chemistry Dr. Declan Gaynor FUNCHEM 11 Introduction to organic chemistry 1 FUNCHEM.11 Learning Outcomes Compare properties of organic and inorganic compounds. Identify and describe structural ge...

Fundamentals of Medicinal and Pharmaceutical Chemistry FUNCHEM.11 Introduction to organic chemistry Dr. Declan Gaynor FUNCHEM 11 Introduction to organic chemistry 1 FUNCHEM.11 Learning Outcomes Compare properties of organic and inorganic compounds. Identify and describe structural geometry and bonding present in organic compounds according to valence bond theory. Interpret and construct Lewis structures, condensed structures and line structures of organic compounds. Identify the following functional groups (alkane, alkene, alkyne, alcohol, thiol, ether, sulphide, aldehyde, ketone, carboxylic acid, amine, amide, ester, halide, acid halide, aromatic). Identify and describe aliphatic and aromatic hydrocarbons. Describe and identify examples of structural, geometric and optical isomers. FUNCHEM 11 Introduction to organic chemistry Understanding organic chemistry is important The enzyme HMG-CoA reductase is an enzyme which catalyses a crucial step in the synthesis of cholesterol in the human body. 3  Introduction What is organic chemistry about? ‘The Chemistry of Carbon Compounds’ Carbon Compounds: Provides Constituents of Living Matter, e.g. DNA, Proteins, Carbohydrates Provides Energy by Conversion to CO2 Gasoline, Oil as an Industrial Feedstock etc…. Why Carbon? Less than 1% of the earth’s crust! ….compare with Si (~28%), O (~50%), Fe (5%) Ability to form chains of atoms ― linear, branched & cyclic Combines with H, N, O (98% of living tissue is derived from these 4 elements) Enormous variety of structures available (3-dimensional) FUNCHEM 11 Introduction to organic chemistry 4  The basic components in organic chemistry Organic Compounds: Compounds made of carbon atoms covalently bonded to each other and to other non-metal atoms, such as H, O, N, S and halogens. (All other compounds are inorganic compounds). FUNCHEM 11 Introduction to organic chemistry 5  Organic compounds vs inorganic compounds Organic Chemistry: The study of the structures, properties and syntheses of organic compounds. Organic Molecules Inorganic Molecules a. Covalent bonds a. Ionic bonds b. Usually are poorly b. Usually are extremely soluble in water soluble in water c. Relatively low melting c. Relatively high melting and boiling points and boiling points FUNCHEM 11 Introduction to organic chemistry 6 Why carbon? Group 4 element Can share 4 valence electrons Can form 4 strong covalent bonds with other carbon atoms and other hetero atoms Can form long chains and cycles Why not silicon? It is group 4 and can form form 4 covalent bonds FUNCHEM 11 Introduction to organic chemistry 7 Carbon summary Atomic number = 6 Has 6 electrons to be divided into shells (and corresponding orbitals) Lowest energy electron configuration: 1s2 2s2 2px1 2py1 Four valence electrons. (the electrons in the outermost shell) Neither strongly electropositive nor strongly electronegative with an electronegativity value of 2.5 Can11form FUNCHEM strong Introduction bonds with neighbouring C to organic chemistry 8  Covalent Bonding anic compounds – compounds of carbon – are held together by covalent bonds valent bonds are formed by sharing of electrons; rganic chemistry the term bond is used to designate a shared pair of electrons bon has four valence electrons; this means it can form a maximum of r covalent bonds nds are represented by a straight line connecting the atoms with each bond resenting a shared pair of electrons ethene ethyne methane CH4 CH2CH2 CHCH four single bonds double bond triple bond to carbon between carbons between carbons H H H H C H C C H C C H H H H 2 electrons in 2 electrons in 2 electrons in a  bond and 2 electrons a  bond and 2 electrons this  bond in a  bond each in two  bonds  Covalent Bonding A sigma () bond is a covalent bond formed by head-on overlap of atomic orbitals All four C-H bonds are identical and spatially orientated towards a regular tetrahedron methane A pi () bond is a covalent bond formed by sideways overlap of atomic orbitals, e.g. carbon-carbon double bonds contain one sigma bond and one pi bond formed by sideways overlap of two p orbitals ethene e.g. carbon-carbon triple bonds contain one sigma bond and two pi bonds (formed by sideways overlap of two p orbitals) ethyne  3D Shape of Organic Compounds Methane Tetrahedral geometry H all four C-H bonds are identical and spatially o 109.5 C orientated towards a regular tetrahedron H H H all C–H bonds are the same length (110 pm); solid line lies in the plane of the page; angles between any pair of bonds is 109.5° the dashed line goes behind the plane; the solid wedge extends out of the plane Ethene H 121.7o H carbon-carbon double bonds containing one sigma bond and one pi bond with length of 133 pm; C C 116.6o C-H bond angle of 121.7° H H Ethyne carbon-carbon triple bonds contain one sigma bond and two pi o 180 bonds with length of 120 pm; H C C H bond angle of 180° Polar covalent bonds From left to right within a given period in periodic table, the elements become more electronegative, owing to increasing charge on the nucleus; Biologically relevant examples: From top to bottom of the 𝛿+ 𝛿- 𝛿+ 𝛿- table within a given group, the C-O C-N 𝛿+ 𝛿- 𝛿+ 𝛿- elements become less electronegative because the O-H C-Cl valence electrons are shielded from the nucleus by FUNCHEM 11 Introduction to organic chemistry 12 Polar covalent bonds A covalent bond where the electron pair is not shared equally between the atoms. Electronegativity determines bond polarization (unequal sharing of electrons in covalent bond). Note: C (2.5) and H (2.2) have very close electronegativity values. FUNCHEM 11 Introduction to organic chemistry 13 wing organic structures: Lewis structures In Lewis symbolism for the illustration of molecular structures: Every valence electron must be shown Valence electrons in covalent bonds (single, double or triple) are symbolised by one or more lines between atoms Unshared valence electrons are symbolised as dots on the atoms to which they belong H H.... H C N H H O.. C H Note: when lone pairs H H H are not shown they are understood to be Methylamine Methylamine Methanol present Unshared electrons that are paired are called lone pairs. FUNCHEM 11 Introduction to organic chemistry 14 awing organic structures: line structures Most convenient form of representation of organic compounds Carbon and hydrogen connected to carbon are generally represented by the end of a line or intersection of lines as displayed Dashed bond pointing away below from viewer End of line – CH3 End of double line - CH2 Wedge bond End of triple line - CH pointing towards viewer Intersection of two lines – CH2 – Intersection of three lines – CH FUNCHEM 11 Introduction to organic chemistry – 15 Organic molecule categories Carbon and other common elements including hydrogen, oxygen, nitrogen, sulphur and halogens A functional group is an atom or group of atoms within a molecule that shows a characteristic set of physical and chemical properties The chemical reactivity of every organic molecule, regardless of complexity or size, is determined by the functional groups it contains Hydrocarbons A hydrocarbon is a compound which contains only carbon and hydrogen An aliphatic hydrocarbon is a non-aromatic hydrocarbon. An aromatic hydrocarbon contains an aromatic ring structure which has specific structure and reactivity FUNCHEM 11 Introduction profile to organic chemistry 16 assification of organic compounds unctional groups are groups of atoms that have characteristic chemical operties regardless of the molecular framework to which they are attached Molecules containing only carbon and hydrogen atoms are called hydrocarbons Functional Groups Structure Family Name Simple Example H H Alkane C C (contains only C-H H C C H ethane & C-C bonds) H H H H C C Alkene C C ethene H H (ethylene) C C Alkyne H C C H ethyne (acetylene) Aromatic benzene FUNCHEM 11 Introduction to organic chemistry 17  Functional groups Structure Family Name Simple Example H H C OH Alcohol H C C OH ethanol H H H H H H C O C Ether H C C O C C H diethyl ether H H H H H H C SH Thiol H C C SH ethane thiol H H H H Sulfide H C S C H dimethyl sulfide C S C (or thioether) H H FUNCHEM 11 Introduction to organic chemistry 18  Functional groups Structure Family Name Simple Example H H C NH2 Amine H C C NH2 ethylamine H H H C N Nitrile H C C N acetonitrile H H C X Halide H C Cl chloromethane (X = Cl, Br, or I) H F F Trifluoromethyl trifluoromethane C F H C F F F FUNCHEM 11 Introduction to organic chemistry 19 Carbonyl functional groups The most important functional group in organic chemistry Polarised covalent carbon – oxygen double bond O - C  + Electronegativity values C = 2.5 O = 3.5 There are many different types of carbonyl compounds FUNCHEM 11 Introduction to organic chemistry 20  Functional groups: carbonyls Structure Family Name Simple Example O O Aldehyde formaldehyde C H H C H O H O H C C C propan-2-one Ketone H C C C H (acetone) H H O H O ethanoic acid C OH Carboxylic acid H C C OH (acetic acid) H O H O H H C O C Ester H C C O C C H ethyl acetate H H H FUNCHEM 11 Introduction to organic chemistry 21  Functional groups: carbonyls Structure Family Name Simple Example O H O acetamide C NH2 Amide H C C NH2 H O H O Acyl halide C X (X = Cl or Br) H C C Cl acetyl chloride H O O H O O H Carboxylic acid acetic Not a carbonyl C O C anhydride H C C O C C H anhydride compound H H ………………………………………………………………………………………….. O H O C O P OH Ester of methyl H C O P OH Phosphoric Acid monophosphate OH H OH FUNCHEM 11 Introduction to organic chemistry 22  Structural isomers Compounds can have identical molecular formula but different structural formulas. Structural (or constitutional) isomers differ in atom to atom connectivity. H H H H Isomers can have totally different H C C physical O H and biological properties. H C O C H Compare H H H H Ethanol Dimethyl ether (liquid) (gas) Molecular formula C2H6O C2H6O Boiling point 78.5 C -23.6 C Melting point -114.3 C -138.5 C Solubility in water Soluble in all Slightly proportions soluble FUNCHEM 11 Introduction to organic chemistry 23  Stereoisomers: geometric isomers Geometric isomers or diastereomers have the same order of attachment of their atoms but a different arrangement of their atoms in space. They are not mirror images of each other. They are often classified as being (cis/trans isomers) cis-but-2-ene trans-but-2-ene  C H : b.p. 4 C  C4H8: b.p. 1 C 4 8 H3C CH3 H3C H C C C C H H H CH3 cis trans (substituents on the same side) (substituents on opposite sides) FUNCHEM 11 Introduction to organic chemistry 24 Which of the molecules shown below are a pair of geometric isomers? FUNCHEM 11 Introduction to organic chemistry 25 Thank you FOR MORE INFORMATION PLEASE CONTANT Dr. Declan Gaynor EMAIL: [email protected] FUNCHEM 11 Introduction to organic chemistry 26  McMurry, ‘Organic Chemistry with Biological Applications’, 3rd Edition, 2015, Cengage Learning Recommended reading Chapter 1 and Chapter 2: general reading on structure, hybridisation, bonding and functional groups. Chapter 3 Section 1: general functional groups. FUNCHEM 11 Introduction to organic chemistry 27  Identify the functional groups amide trifluoromethyl phenyl/aromatic H O N C F F CH3 F HN amine HO alcohol O (phenol) ether Paracetamol Prozac primary H3C O amide alcohols O C CH2OH CH2OH N H O O O O OH H OH hemi- O OH H acetal ether CH3 O CH HO 3 H OH ether H OH secondary (acetal) alcohols Trimetozine Maltose FUNCHEM 11 Introduction to organic chemistry 28  Identify the functional groups carboxylic alkenes acid CO2H amine alcohol Dopamine C-5 alkyl (phenol) Arachidonic acid carboxyli O c acid C alcohol OH OH CH2 O O H2N C C carboxyli ester C H OH c O CH3 amine acid Serine Aspirin FUNCHEM 11 Introduction to organic chemistry 29