Lecture 3: Alkanes and Cycloalkanes PDF

Pharmaceutical Organic Chemistry I PC101 Alkanes & Cycloalkanes Mona S. El-Zoghbi, Ph. D. Pharm. Sc. Associate professor of pharmaceutical Chemistry Pharmaceutical Chemistry Department [email protected] Intended learning outcome...

Pharmaceutical Organic Chemistry I PC101 Alkanes & Cycloalkanes Mona S. El-Zoghbi, Ph. D. Pharm. Sc. Associate professor of pharmaceutical Chemistry Pharmaceutical Chemistry Department [email protected] Intended learning outcomes of the course (ILOs) On successful completion of the course, you should be able to: ❖Recognize several organic terms. ❖Underline the different types of chemical bonds. ❖Recognize the different classes of organic compounds. ❖Assess the structural feature of organic compound and its IUPAC name. ❖Demonstrate alkanes, alkenes, alkynes and alkyl halides (nomenclature, physical and chemical properties, preparation and chemical reactions). ❖ Classify different reaction mechanism. ❖ Outline fundamental principles and applications of stereochemistry, stereo-dynamic, hydroxyl and carbonyl compounds. ❖ Identify the principles of aromaticity and benzenoid compounds.  Organic Compounds Acyclic Cyclic Open chain aliphatic compounds Carbocyclic Heterocyclic Alicyclic Aromatic  Organic compounds: Are compounds containing carbon in C-C bonding. Organic comes from organism as they were first discovered in living organisms. Carbocyclic compounds: Are cyclic organic compounds containing carbon and hydrogen only. Alicyclic compounds: Are saturated cyclic organic compounds containing carbon and hydrogen only. They have the same properties of aliphatic compounds, they behave like alkanes eg. cyclopropane, cyclohexane. Aromatic compounds: Are carbocyclic compounds containing benzene ring or they are cyclic compounds having low H/C ratio. eg. Benzene, naphthalene.  Heterocyclic compounds: Are cyclic organic compounds containing one or more heteroatom as nitrogen, sulphur or oxygen. eg. N O S pyridine, furan, thiophen.  Aliphatic Hydrocarbons They are open chain organic compounds containing carbon and hydrogen. They are classified into: Saturated Unsaturated Alkanes Alkenes Alkynes Contain double bond Contain triple bond. I- Saturated Hydrocarbons "Alkanes" "CnH2n+2" where n is the number of carbon atoms Nomenclature of alkanes: common names “trivial names” I.U.P.A.C. system "International Union of Pure and Applied Chemistry" I.U.P.A.C. system "International Union of Pure and Applied Chemistry" No of carbons Name Formula 1 Methane CH4 2 Ethane C2H6 3 Propane C3H8 4 Butane C4H10 5 Pentane C5H12 6 Hexane C6H14 7 Heptane C7H16 8 Octane C8H18 9 Nonane C9H20 10 Decane C10H22 11 Undecane C11H24 12 Dodecane C12H26 13 Tridecane C13H28 14 Tetradecane C14H30  longest and continuous chain the parent CH2 CH2 CH3 CH3 CH2 CH CH2CH2 CH3 “4-Ethylheptane” more than one chain of equal length the more substituted chain CH3 CH3 CH CH3 CH CH3 CH3 CH2 CH2 C CH2 CH3 CH3 CH2 CH2 C CH2CH3 CH3 CH3 2- substituents only 3- substituents Number the chain and begin at the end that gives the lowest number to the substituents. CH3 CH CH3 CH3 CH2 CH2 C CH2CH3 CH3 "3- Ethyl-2,3-dimethyl hexane" Two or more identical groups prefixes di-, tri- and tetra- Ordering the groups in alphabetical order di-, tri- and tetra- are not considered in alphabetical order The numbers are separated by commas, while numbers and letters are separated by dashes. CH3 eg. CH3 CH2 C CH2 CH3 CH3 "3,3-Dimethylpentane "Iso" and "tertiary are considered in alphabetical order CH3 CH3 CH CH3 CH2 CH3 eg. CH3 CH CH CH CH2 C CH2 CH3 CH3 CH2CH3 "6,6-Diethyl-4-isopropyl-2,3-dimethyloctane" b) Common names “trivial names”: 1) Normal alkanes: "n" straight continuous chains with no branching eg. CH3–CH2–CH2–CH2–CH3. n-pentane 2) Isoalkanes: "iso" two methyl groups located at one end of the side chain CH3 CH2 CH3 CH CH3 CH3 CH CH2 CH2 CH2 CH3 "isobutane" isoheptane  3) Neoalkane : "neo" there are three methyl groups located at one end of the chain. CH3 CH3 CH3 C CH3 CH3 CH CH2 CH3 CH3 "neopentane" "isopentane" C) Alkyl groups: They are obtained by the removal of one hydrogen from alkane. Then remove the suffix "-ane" and replace it with “-yl". eg. Methane →methyl "CH3–" Ethane → ethyl CH3–CH2 - Propane → propyl -H eg. CH3 CH2 CH3 CH3 CH2 CH2 "n-propyl" -H CH3 CH "isopropyl" CH3  Preparation of alkanes I- From unsaturated hydrocarbons 1) By catalytic reduction Ni or Pd (a) C C + H2 CH CH Ni (b) C C + H2 CH2 CH2 II. From alkyl halides 1) Reduction of alkyl halides Zn/HCl or HAc R X R H or Mg/Hg/EtOH H2 / Ni R X or LiALH4 R H The same number of carbon atoms. 2) Wurtz reaction ether R X + Na solvent R R X CH3 CH3. Na CH3 CH CH3 CH3 CH CH CH3 ether Double the number of carbon atoms 3) From Gringard reagent: ether R X + Mg R MgX "alkyl halide" "alkylmagnesium halide" "Gringard reagent" H2O or H + R H + Mg(OH)X The same number of carbon atoms as alkyl halide. III- From carbonyl compounds: O reduction C CH2 The same number of carbon atoms Reduction is carried out either by Clemmenson reduction : Zn/Hg/HCl. Wolf-Kischner reduction: NH2–NH2/base (NaOH or NaOC2H5). IV- From carboxylic acids 1) By decarboxylation of carboxylic acids and their salts CaO/NaOH RCOOH R H + CO2 (Sodalime) or RCOO - Na+ one carbon less than the starting material  Reactions of alkanes sp3hybridized carbon atoms bond angle is 109.5º non-polar inert unreactive possessing strong sigma bonds I. Halogenation of alkanes A substitution reaction High temperature ( i.e. 250 - 400ºC) or in presence of light Free radical mechanism The rate of halogenation by fluorine is faster than chlorine than bromine than iodine Chlorine is more reactive and non selective, while bromine is less reactive but selective It reacts with 3º hydrogen rather than 2º than 1º light or CH4 + Cl2 CH3Cl + HCl high temp. "chloromethane" h.v h.v/Cl2 CH4 + Cl2 CH3Cl CH2Cl2 h.v/Cl2 CHCl3 h.v/Cl2 CCl4 It is called a chain reaction  CH3 CH3 Br2/h.v. eg. CH3 CH CH2 CH3 CH3 C CH2 CH3 3o 2o Br Cl2/h.v. "main product" CH3 CH2Cl CH3 CH3 C CH2 CH3 + CH3 CH CH2CH3 + CH3 CH CH CH3 Cl Cl CH3 CH CH2 CH2 Cl CH3 II. Nitration: The use of concentrated nitric acid at 500ºC Replace a hyrogen atom by a NO2 group Conc. HNO3 CH3 CH2 CH3 CH3 CH CH3 + CH3 CH2 CH2 500oC NO2 NO2 + CH3 CH2 NO2 + CH3 NO2 free radical mechanism "nitroethane" "nitromethane" III. Sulphonation: CH3 CH3 oleum or fuming sulphuric acid CH3 CH CH3 CH3 C CH3 (c.H2 SO4 /SO3) SO3H "1,1-dimethyl ethane sulphonic acid'" Substitution by sulphonic group occurs to tertiary hydrogen and to less extent to secondary hydrogen however, sulphonation may not occur to primary hydrogens IV. Oxidation: CnH2n+2 O2 or air CO2 + H2O + large amount of heat 500-700oC This reaction gives a large amount of heat that is why alkanes are used as fuel. V. Pyrolysis of alkanes "cracking". thermal decomposition of the compound occurs by heating at high temperature in absence of oxygen - H2 alkene 500oC CnH2n+2 rupture of C C bond absence of O2... smaller alkanes smaller alkenes eg. 600oC CH3 CH2 CH3 CH3 CH CH2 + CH3 CH3 + CH4 + CH2 CH2 Alicyclic compounds (Cycloalkanes)  Alicyclic compounds (Cycloalkanes) They are alkanes having the carbons arranged in a ring They have the general formula CnH2n Nomenclature: Name according to the number of carbon atoms, then give it the prefix “cyclo-”. CH2 CH2 CH2 cyclopropane Give the substituent number one unless there is more than one substituent, give them the lowest possible numbers. CH3 H 3C CH3 COOH CH2CH3 CH2CH3 "1-Ethyl-3-methylcyclohexane" "cyclohexane carboxylic acid'" 3-Ethyl-1,1-dimethylcyclo pentane"  If the side chain has greater number of carbon atoms than the ring the ring is considered as a substituent to the side chain. Remove the suffix "–ane”, and replace it by "–yl" to be a radical. Moreover, cyclo is considered in the alphabetical order. CH3 eg. CH2 CH CH2CH3 1-cyclopropyl-2-methylbutane Trivial names: They are named as polymethylene derivatives. eg. trimethylene, pentamethylene Preparation: 1- By dehalogenation of α, ω -dihalogen derivatives: internal Wurtz reaction the two halogen atoms must not be separated by more than six atoms if more than six atoms intermolecular Wurtz reaction Zn or Na eg. Br CH2 CH2 CH2 Br + ZnBr2 or 2 NaBr "1,3-dibromopropane" Zn eg. Br CH2 CH2 CH2 CH2 CH2 CH2 Br + 2 ZnBr2 Na eg. Br CH2 CH2 CH2 CH2 CH2 CH2 CH2 Br H3C (CH2)12 CH3 "tetradecane" 2. From other cyclic compounds: H2/Ni "cyclopentene" cyclopentane O Zn/Hg/HCl "Clemmenson reduction" "cyclopentanone" 3. Reduction of Benzene derivatives: H2/Ni eg. / pressure Benzene cyclohexane Double bonds of benzene are highly stable require high temperature and pressure to break the aromaticity. Reactions of cycloalkanes: “Baeyer Strain theory” they should have tetrahedral orientation Cycloalkanes have sp3 hybridized carbons the bond angle should be 109.5º three membered rings eg. cyclopropane will have bond angle They are cyclic equal to 60º four membered rings as cyclobutane their bond angle will be 90º five membered rings as cyclopentane their bond angle will be 108º six membered ring like cyclohexane their bond angle will be 120º As the difference from tetrahedral angle increase the strain will increase and the stability of the ring decreases  Three and four membered rings are highly strained they are very reactive and ring opening occur in order to remove the strain five membered rings have no strain six membered rings are very stable and are found in "puckered conformations". bond angle is 108o which or is not far from 109.5o boat conformation" "chair conformation" Five and six membered rings do not undergo ring opening as three and four membered rings do 1-Hydrogenation: 80oC + H2/Ni CH3 CH2 CH3 200oC + H2/Ni CH3CH2CH2CH3 or + H2/Ni no reaction 2-Electrophilic addition reactions: CH3 Br CH Br2 CH3 CH CH2 CH2 Br CH2 CH2 conc. HI CH3 CH CH2 CH3 I + H2O/H CH3 CH CH2 CH3 OH Reactions of five and six membered rings: They do not undergo ring opening but they carry out the normal substitution reactions of alkanes H Cl eg. + Cl2/h.v + HCl Cl OH NaOH Cyclohexanol. alc. KOH Cyclohexene CN KCN