Pharmaceutical Organic Chemistry-1 PC102 Lec.4 PDF

Pharmaceutical Organic Chemistry-1 PC102- Lec.4 Dr Samar Samir Tawfik [email protected] Dr Selwan Mahmoud [email protected]  Intermolecular Forces (Non-covalent interactions): It does not involve the sharing of electrons, but rather involves ele...

Pharmaceutical Organic Chemistry-1 PC102- Lec.4 Dr Samar Samir Tawfik [email protected] Dr Selwan Mahmoud [email protected]  Intermolecular Forces (Non-covalent interactions): It does not involve the sharing of electrons, but rather involves electromagnetic interactions between molecules or within a molecule. 1. Van der Waals Forces (Dispersion Forces) 2. Dipole-Dipole Forces 3. Ion-Dipole Forces (Salt dissolving in solution) 4. Hydrogen Bonds  1. Van der Waals Forces (London forces or Dispersion Forces) Occurs when adjacent atoms come close enough that their outer electron clouds just touch. They are highly distance dependent and are the weakest of all non-covalent interactions. Significant only in combined interactions. The larger the molecule, the greater its dispersion force. Theory:  The electrons move, so the electrons and the charge are not uniformly distributed, so a small temporary dipole will occur.  This temporary dipole in a molecule produces opposite (attractive) dipoles in surrounding molecules.  The net result is producing attractive forces between molecules.  Deviation of Boiling Points can be explained by Van der Waals forces: - The straight chain isomer of n-pentane (zig zag) with the greatest surface area, the greater the Van der Waals forces and the higher boiling points. - A branched chain isomer iso-pentane has smaller surface area. This isomer has the lower boiling point than the straight chain isomer. - Neopentane with the most branching has the lowest boiling point since it has the least surface area. Exercise: Compare between the boiling points of the following isomers  2. Dipole-Dipole Forces  Occur between polar molecules due to electrostatic interactions among dipoles.  Forces can be attractive or repulsive depending on orientation of molecules.  3. Ion-Dipole Forces (Salt dissolving in solution)  The force of attraction between an ion and a polar molecule.  The charge of the ion will attract the opposite partial charge of the dipole.  Na+ is a cation, so it attracts the slightly –ve end of water (the oxygen).  4. Hydrogen bonds: It is a strong dipole-dipole interaction which occurs between H-atom bonded to small strongly electronegative atoms (O, N or F) and the nonbonding electron pairs on other such electronegative atom. Usually the electronegative atom is oxygen, nitrogen, or fluorine, which has a partial –ve charge. The hydrogen then has the partial +ve charge. Stronger than normal dipole forces between molecules. When H-bonds connect separate molecules, they are called intermolecular H-bonds (association). When H-bonds connect groups within the same molecule, they are called intramolecular H-bonds (chelation).  Phenomena Explained by hydrogen bond forces: a) Deviation of Boiling Points:  b) Like dissolves like: Because alcohols can interact by hydrogen bonding with water, they are more soluble in water than alkanes of comparable molecular weight. e.g. methanol, ethanol, 1-propanol. Alcohols of higher molecular weight are much less soluble in water because of the increase in the size of hydrocarbon portion of the molecule. e.g. decanol (soluble in non-polar solvent e.g. hexane).  c) Variation in physical characters between nitro phenols: o-nitrophenol is more volatile than m- and p-nitrophenol (as it can form intramolecular H-bond (chelation).  Concepts of Acidity and Basicity An acid: substance that gives a proton (H+) to another substance. A base is a molecule or ion able to accept a hydrogen ion from an acid. Conjugate base: the species formed from an acid when it donates a proton to a base. (The stronger the acid, the weaker its conjugate base) Conjugate acid: the species formed from a base when it accepts a proton from an acid. E.g. Chloride is a very weak base because its conjugate acid HCl is a very strong acid.  Lewis acid and base: Lewis acid: accept electron pair and are electrophiles. Atoms with an empty valence orbital can be Lewis acids as BF3, AlCl3, FeCl3, SbCl3, ZnCl2, HgCl2. Lewis base: donate an electron pair and are Nucleophiles meaning that they “attack” a positive charge with their lone pair.  AlkaNes & Cycloalkanes Saturated Hydrocarbons A series of compounds that contain carbon and hydrogen atoms with single covalent bonds. Molecular formula CnH2n+2 Simplest and least reactive of all organic compounds. Examples: methane, ethane. Non-polar molecules. (why?) The only interactions between molecules are Van Der Waals interactions.  Water insoluble. Soluble in non polar solvents as they are hydrophobic molecules. Liquid alkanes are lighter than water. Cycloalkanes have higher boiling points than corresponding straight chains. Isomers: compounds that contain exactly the same number of atoms but differ from each other by the way in which the atoms are arranged, so their properties are different. (Constitutional isomers)  Nomenclature of alkanes A) Common nomenclature of alkanes 1. The total number of carbon atoms in an alkane, regardless of their arrangement, determines the name. 2. The first three alkanes are methane, ethane, and propane. 3. Alkanes with 4 carbons are butanes, 5 carbons are pentanes, 6 carbons are hexanes. 4. For alkanes beyond propane, normal, or n- is used to indicate that all carbons are in a continuous chain, iso is used to when one end of continuous chain terminates in a (CH3)2CH-group, neo is used to indicate that one end of a chain terminates in (CH3)3C-. 5. Hydrogens are also classified as primary (1), secondary (2), or tertiary (3) depending on the type of carbon to which each is bonded.  B) IUPAC nomenclature of alkanes: The International Union of Pure and Applied Chemistry (IUPAC) established a set of rules for naming alkanes. The name of alkane consists of a prefix represents the number of carbons and a suffix –ane. A substituent group derived from alkane by removal of an H atom is called an alkyl group. The symbol R- is commonly used to represent an alkyl group. Alkyl groups are named by dropping the -ane from the name of the parent alkane and adding the suffix –yl e.g., ethane gives ethyl... etc.  IUPAC system rules for naming alkanes: 1. For branched-chain alkanes, the hydrocarbon derived from the longest chain of carbon atoms is taken as the parent chain. 2. Group(s) attached to the parent chain is called substituent(s). Each substituent is given a name and number that shows the carbon atom of the parent chain to which the substituent is attached. 3. If the same substituent occurs more than once, the number of each carbon of the parent chain on which the substituent occurs is given. In addition, the number of time the substituent group occurs is indicated by a prefix di-, tri-, tetra-, penta-, hexa-, hepta-, octa-, nona-, deca-, and so on. 4. If there is one substituent, number the parent chain form the end that gives it the lower number. 5. If there are two or more identical substituents, number the parent chain from the end that gives the lower number to the substituent encountered first. 6. If there are two or more different substituents, list them in alphabetical order and number the chain form the end that gives the lower number to the substituent encountered first. If there are different substituents in equivalent position on the parent chain, the substituent of lower alphabetical order is given the lower number. 7. When branching first occurs at an equal distance from either end of the longest chain, choose the name that gives the lower number at the first point of difference.  Hyphenated prefixes, such as sec- and tert-, are not considered when alphabetizing.  The prefix iso- is not a hyphenated prefix and, therefore, is included when alphabetizing e.g.:  Branches or R groups or substituents names: “ane” changed to yl = alkyl (methyl, ethyl, propyl, etc) Nomenclature of cycloalkanes: