Pharmaceutical Organic Chemistry: Hydrocarbons PDF

Pharmaceutical Organic Chemistry: Hydrocarbons NESTOR TORDZAGLA (PhD)  Introduction Jons Berzelius (1779-1848), a Swedish scientist, began using the term organic to refer to substances isolated from living systems. It was believed that since life itself was not understandable...

Pharmaceutical Organic Chemistry: Hydrocarbons NESTOR TORDZAGLA (PhD)  Introduction Jons Berzelius (1779-1848), a Swedish scientist, began using the term organic to refer to substances isolated from living systems. It was believed that since life itself was not understandable, organic compounds also were not understandable. Organic Chemistry became a distinct branch of science in the early 1800s. They recognized that compounds could be characterized by their chemical properties and began to assign specific properties to specific compounds. Today, organic chemistry is defined as the chemistry of the compounds of carbon. This definition is not entirely correct, because a few carbon compounds, such as carbon dioxide, sodium carbonate, and potassium cyanide, are considered to be inorganic. We accept this definition, however, because all organic compounds do contain carbon.  Introduction Carbon is but one element among many in the periodic table. What is so unique about carbon that its compounds justify a major subdivision in the study of chemistry? The answer is that carbon atoms can be covalently bonded to other carbon atoms and to atoms of other elements in a wide variety of ways, leading to an almost infinite number of different compounds. Some of these compounds are simple, example, methane while others are complex eg. Nucleic acids, the carriers of the genetic code in living systems. A knowledge of organic chemistry is indispensable to many scientists. We have many classes of organic compounds, one of them is a hydrocarbon.  Introduction Hydrocarbons are compounds which contain only carbon and hydrogen atoms There are two main classes of hydrocarbons namely, aliphatic and aromatic. Aliphatic hydrocarbons include three main groups; alkanes, alkenes and alkynes Aromatic hydrocarbons or arenes are aromatic organic compounds containing solely carbon and hydrogen atoms. Example, benzene  Introduction A functional group is the structural unit responsible for the reactivity of a given molecule under a particular set of conditions. It can be as small as a single hydrogen atom or several atoms. A hydrogen atom is a functional unit in alkanes. Key functional groups in organic chemistry include alcohol, alkyl halide, amine, epoxide, ether, nitrile, nitroalkane, thiol, carbonyls, arenes. Carbonyl-containing compounds rank among the most abundant and biologically important classes of naturally occurring substances. Carbonyl-containing compounds include aldehyde, ketone, carboxylic acid, carboxylic acid derivatives (acyl halide, acid anhydride, ester, amide)  ALKANES Alkanes have the general molecular formula CnH2n+2 Petroleum is the primary source of alkanes The simplest and the most abundant alkane is methane (CH4) Ethane (C2H6) and propane (C3H8) are the second and third most abundant respectively Natural gas consists of ≈ 75% methane together with ethane (≈ 10% ) and propane (≈ 5% ) Liquefied petroleum gas (LPG) is mainly propane-rich mixture of hydrocarbons liquefied under high pressure. Nomenclature in organic chemistry is of two types; common or trivial and systematic.  Shapes of Alkanes All the carbon atoms of alkanes are sp3-hybridized, the bonds are σ bonds and the orientation of the groups is close to tetrahedral.  NOMENCLATURE OF ALKANES: RULES 1. Count the longest continuous carbon chain and name it as the parent structure. 2. Any group of atoms which do not form part of the parent structure is called a substituent or side group. NOTE: the names of all side groups come before the name of the parent structure. 3. There are two types of substituents: a) Inorganic substituents: bromo, chloro, iodo, amino, nitro, hydroxyl, cyano, etc b) Organic substituents: They are mainly alkyl groups with general molecular formula CnH2n+1. Examples are methyl, ethyl, propyl, phenyl, etc.  NOMENCLATURE OF ALKANES: RULES 4.If the alkane contains a mixture of substituents, all inorganic groups are named first in alphabetical order before the organic substituents, also in alphabetical order. 5. When two chains of equal length compete for selection as the parent chain, choose the chain with the greater number of substituents.  NOMENCLATURE OF ALKANES: RULES 6. The position of the substituent on the parent structure is indicated with the least possible number. 7. If a substituent occurs two or more times, the number of times is indicated by the Greek prefixes di, tri, tetra, etc, for 2, 3, 4, respectively. 8. In naming, numbers are separated from each other by commas and numbers from names by hyphens. TRIVIAL AND IUPAC NAMES OF COMMON ALKYL GROUPS Nomenclature of Branched Alkyl Groups Nomenclature of Branched Alkyl Groups Nomenclature of Branched Alkyl Groups NOMENCLATURE OF ALKANES NOMENCLATURE OF ALKANES NOMENCLATURE OF ALKANES NOMENCLATURE OF ALKANES  NOMENCLATURE OF CYCLOALKANES Cycloalkanes are saturated cyclic hydrocarbons Have the general formula (CnH2n) Count the number of carbon atoms in the ring and the number in the largest substituent chain. If the number of carbon atoms in the ring is equal to or greater than the number in the substituent, the compound is named as an alkyl-substituted cycloalkane For an alkyl- or halo-substituted cycloalkane, start at a point of attachment as C1 and number the substituents on the ring so that the second substituent has as low a number as possible. Number the substituents and write the name NOMENCLATURE OF CYCLOALKANES  NOMENCLATURE OF CYCLOALKANES 1,1,4-trichlorocyclodecane 4-iodo-1,1-diethylcyclohexane trans-1-bromo-3-ethylcyclohexane NOMENCLATURE OF CYCLOALKANES NOMENCLATURE OF CYCLOALKANES Classification of Carbon and Hydrogen Atoms  ISOMERISM Isomerism in organic chemistry is a phenomenon shown by two or more organic compounds having the same molecular formula but different properties due to difference in arrangement of atoms along the carbon skeleton (structural isomerism) or in space (Stereo isomerism).  Isomerism in Alkanes Methane, ethane and propane are the only alkanes with the molecular formula CH4, C2H6, and C3H8 respectively However, with alkanes of four carbons and more, constitutional isomers are possible. For example, C4H10 has n-butane and isobutane as constitutional isomers. Isomerism in Alkanes  Isomerism in Alkanes 𝐶5 𝐻12 has three constitutional isomers; n-pentane, iso-pentane and neo- pentane. How many isomers can be written for 𝐶6 𝐻14 ?  Physical Properties of Alkanes A series of compounds in which each member differs from the next member by a constant unit, is called a homologous series. Members of a homologous series are homologs. At temperature (25 0C) and 1 atm pressure, the C1-C4 unbranched alkanes are gases, the C5-C17 unbranched are liquids, the unbranched C18 or more are solids. The boiling points of unbranched alkanes show a regular increase with increasing molecular weight.  Physical Properties of Alkanes Branching chain lowers the boiling point of alkanes  Physical Properties of Alkanes Solubility Alkanes and cycloalkanes are almost totally insoluble in water because of their inability to form hydrogen bonds Soluble generally in solvents of low polarity.  Conformations of Alkanes Conformations are different spatial arrangements of a molecule resulting from rotation of groups about single bonds. Conformational analysis of ethane Ethane have two distinct conformations; staggered and eclipsed conformations Staggered conformation Eclipsed Conformation  Conformational Analysis of Ethane The staggered conformation has the lowest energy and hence the most stable. The eclipsed conformation has the highest energy and therefore the least stable Each H–C–C–H unit in ethane is characterized by a torsion angle or dihedral angle Destabilization that arises from eclipsed bonds on adjacent atoms is referred to as torsional strain Steric strain is the total strain of all of the spatially dependent features.  Conformational Analysis of Butane Which conformer is the most stable? Which conformer is the least stable?  Chemical Reactions of Alkanes Alkanes react with chlorine and bromine when heated  Synthesis of Alkanes and Cycloalkanes Hydrogenation of alkenes and alkynes Alkenes and alkynes react with hydrogen in the presence of metal catalyst such as nickel, palladium and platinum to produce alkanes  Synthesis of Alkanes and Cycloalkanes Reduction of alkyl halides Most alkyl halides react with zinc and aqueous acid to produce an alkane  Synthesis of Alkanes and Cycloalkanes Alkylation of terminal alkynes The acetylenic hydrogen is weakly acidic (pKa~ 25) and can be removed with a strong base (eg NaNH2) to give an anion called alkynide anion or acetylenic ion. Alkylation of the acetylenic ion and subsequent hydrogenation produces an alkane.  Alkenes An alkene is a hydrocarbon with one double bond. Alkenes are some sometimes called olefins, an old name for ethylene (CH2=CH2). Alkenes are unsaturated hydrocarbons with the general molecular formula 𝐶𝑛 𝐻2𝑛 where n≥2. Alkenes are generally more reactive than their related alkanes due to the presence of a double bond in their carbon skeletons and relative instability of the pi bond. The two carbons atoms in ethylene are in the sp2 hybrid state with the bond angle of 1200 Rotation is restricted around the double bond  Nomenclature of Alkenes Alkanes are named by counting the longest continuous carbon chain containing the double bond and that is considered the parent structure. The ending “ane” of the corresponding alkane name is changed to “ene”.  The position of the double bond is indicated in the naming with the least possible number. All substituents are named as in alkanes. Trivial names of some alkenyl groups Structure Name Example CH - Methylene 2 =CH 2 Methylenecyclohexane CH =CH- Vinyl CH =CHCl 2 2 Vinyl chloride CH =CHCH - Allyl CH =CHCH Br 2 2 2 2 Allyl bromide  Nomenclature of Alkenes C𝐻3 CH=C𝐻2 Propene C𝐻3 CH=CHC𝐻3 2-Butene or But-2-ene (C𝐻3 )3 C(C𝐻2 )2 𝐶(C𝐻3 )=C(CI) C𝐻3 Nomenclature of Alkenes Nomenclature of Alkenes NOMENCLATURE OF DIENES Addition of Hydrogen Halides to Alkenes Hydrogen halides add to the pi bonds of alkenes to yield alkyl halides. For symmetrical alkenes, only one possible product. CH2=CH2 +HX →CH3CH2X Ethylene an alkyl halide Markovnikov’s Rule If an alkene is unsymmetrical, there is the possibility of two different products from HX addition. CH3CH2=CH2 +HCl →CH3CH2CH2Cl or CH3CHClCH3 Propene 1-chloropropane or 2-chloropropane By Markovnikov’s rule, we predict that reaction of propene with HCl yields 2-chloropropane not 1-chloropropane  Oxidation of Alkenes Alkenes can be converted to 1,2-diols by reaction with cold alkaline potassium permanganate or osmium tetroxide.  Alkynes Alkynes are unsaturated hydrocarbons with the general molecular formula 𝐶𝑛 𝐻2𝑛−2 where n≥2. Nomenclature of Alkynes Count the longest continuous carbon chain containing the triple bond and that is considered the parent structure. The ending “ene” for alkenes is changed to “yne”. All the other rules for alkenes hold for alkynes.  Nomenclature of Alkynes CH≡CH Ethyne C𝐻3 C≡CH Propyne (C𝐻3 )3 CC≡CC(C𝐼2 ) C𝐻2 C𝐻3 Hydrogenation of Alkynes