Pharmaceutical Chemistry Lecture Notes PDF

PL1001 Pharmaceutical Chemistry ORBITAL HYBRIDISATION Lecture 1 Dr Alberto Di Salvo Recommended reading Organic Chemistry by Clayden, Greeves, Warren and Wothers. Organic Chemistry by Loudon (4th edition). Organic Chemistry by G Solomon & C Fryhle (7th edition, 2000). Al...

PL1001 Pharmaceutical Chemistry ORBITAL HYBRIDISATION Lecture 1 Dr Alberto Di Salvo Recommended reading Organic Chemistry by Clayden, Greeves, Warren and Wothers. Organic Chemistry by Loudon (4th edition). Organic Chemistry by G Solomon & C Fryhle (7th edition, 2000). All general chemistry and organic chemistry textbooks do have a section on atomic orbitals and orbital hybridisation Introduction Atomic orbitals represent, with approximation, where electrons are statistically most likely to be found with respect to the nucleus s orbitals have spherical shape, p orbitals have 2 lobes along X, Y and Z axis atomic orbitals are shared when atoms come together to form molecules through covalent bonding Recently actual “picture” of atomic orbitals obtained with a Field Emission Electron Microscope s orbital on the left hand side and p orbital on the right hand side first ever image of atomic orbitals Adapted from I. M. Mikhailovskij et al, Physical Review B 2009, 80, 165404 Hybridisation to hybridise means to mix, in this case mixing orbitals Linus Pauling (above), Nobel Prize in Chemistry 1954, set the foundations of modern quantum chemistry. according to Pauling, hybridisation of atomic outer orbitals must occur before atoms can combine to form molecules this often requires “promotion” of an electron from an s orbital to a p orbital in order to be able to hybridise them Hybridisation, shape of an s and p hybrid orbital The most common elements in Pharmaceutical Science Hydrogen (H): 1s1 Carbon (C): 1s2 2s2 2p2 Nitrogen (N): 1s2 2s2 2p3 Oxygen (O): 1s2 2s2 2p4 The building blocks of the human body H OH OH H2N H O NH2 HO O HO OH H OH N N amino acids H H N N carbohydrates HO O H H H H OH H H nucleic acids H H HO lipids Electronic configuration of the carbon atom C has 6 electrons [1s2 2s2 2p2], 4 in the outer shell [2s2 2p2] Hybridisation states of carbon atom Elemental C has 6 electrons [1s2 2s2 2p2], 4 in the outer shell [2s2 2p2] The most common hybridisation states and geometries found in carbon atoms are: sp3 Tetrahedral sp2 Trigonal planar sp Linear  sp3 hybridised carbon in the molecule of methane (CH4) C has 6 electrons [1s2 2s2 2p2], 4 in the outer shell [2s2 2p2] methane has formula (CH4), therefore C must form 4 equivalent C-H bonds 2p E 2s 1s Ground state 2p sp3 E 2s E 1s 1s Electron promotion Hybridisation  sp3 hybridised carbon in the molecule of methane (CH4) 2s 2px 2py 2pz + MIX sp3 sp3 sp3 sp3 4 equivalent sp3 orbitals – 4 equivalent σ bonds in 3 dimensions the bond angle of sp3 orbitals is 109.5 sp3 hybridised carbon is tetrahedral  sp2 hybridised carbon in the molecule of ethene (C2H4) 2p E 2s 1s Ground state 2p 2p E 2s E sp2 1s 1s Electron promotion Hybridisation sp2 hybridised carbon in the molecule of ethene (C2H4) ethene (C2H4) is another example of an sp2 hybrid the 2 2pz orbitals of the C combine to form a π-bond  sp hybridised carbon in the molecule of ethyne (C2H2) 2p 2p E 2s E sp 1s 1s Electron promotion Hybridisation In ethyne, each carbon forms two σ bonds and two π bonds. Each carbon atom forms a σ bond with a hydrogen atom, a σ bond with the other carbon atom and two π bonds with the other carbon atom. Each carbon undergoes sp hybridisation, where one 2s orbital and one 2p orbital mix to form two equivalent sp hybrid orbitals. H-C≡C-H sp hybridised carbon in the molecule of ethyne (C2H2) 2py 2pz 2s 2px MIX sp sp 2py 2pz + sp hybridised carbon in the molecule of ethyne (C2H2) In addition to the sp hybrid orbitals, each carbon atom has two half-occupied p orbitals, oriented at right angles to each other, and to the interatomic axis. The result is a linear molecule in which the bond angle between carbon and hydrogen atoms is 180o. Carbon atom bond properties Bond strength Evidence for -bonding comes from bond dissociation energies. The dissociation for C=C is not twice that of C─C and that of C≡C is not three times C─C. – H (C─C) 348 kJmol-1 – H (C=C) 612 kJmol-1 – H (C≡C) 837 kJmol-1 -bonding is weaker than -bonding. Bond length Bond type length (pm) C-C 154 C=C 133 C≡C 120 Hybridisation state of nitrogen atom Elemental N has 7 electrons [1s2 2s2 2p3], 5 in the outer shell [2s2 2p3] Nitrogen has prevalent hybridisation states: sp3 Tetrahedral sp2 Trigonal planar More sp3 hybrids – ammonia (NH3) N has 7 electrons [1s2 2s2 2p3], 5 in the outer shell [2s2 2p3] bond angle measurements indicate tetrahedral geometry pyramidal shape due to stronger repulsion by the lone pair 2p E 2s sp3 E 1s 1s Ground state Hybridisation Hybridisation state of oxygen atom Elemental O has 8 electrons [1s2 2s2 2p4], 6 in the outer shell [2s2 2p4] Oxygen has a prevalent hybridisation state: sp3 Tetrahedral More sp3 hybrids - water O has 8 electrons [1s2 2s2 2p4], 6 in the outer shell [2s2 2p4] bond angle (104.5O) measurements indicate tetrahedral geometry bent shape due to stronger repulsion by 2 lone pairs 2p sp3 E 2s E 1s 1s Ground state Hybridisation