1Course Code: CHM 203Course Title: Organic Chemistry IINumber of Units: 2 UnitsCourse Duration: Two hours per weekCourse Details:Lecturer: Miss Adedo, K.O (B Sc., M Sc)E-mail: email@example.comOffice Location: Islam BlockCourse Content:StereochemistryMethane, energy of activation and free radicals Substitution reactions in alkanesFunctional Group chemistryElectrophilic and Nucleophilic Substitution ReactionAromaticityVarious organic Reactions, e.g addition of free radicals, elimination reactions
2Lecture NotesSUBSTITUTION REACTION OF ALKANEAlkane has been found to undergo substitution reaction, i.e replacement of hydrogen with afunctional group. This substitution reaction can be transformed to other organic compoundsthrough a reaction that occur at the site of the functional group. It is important to note that theC―H bond of an alkane is not polar; hence alkane does not react with nucleophylic orelectrophylic reagents. Equally alkane is not a bronsted acid or bases and is inert to them too.However, alkane requires some reagents and reaction conditions suitable for substitution ofhydrogen atom by a functional group.Halogenation Reaction of AlkaneThe oldest known substitution reaction of alkane is chlorination. This occur in the presence ofUV or bright sun light, hence it is an example of photo-chemical reactions.R―H + Cl2 ―→ R―Cl + HCl [R can be benzene, aliphatic (alkyl) or cyclic (aryl) group.Dumas was the first scientist to observe that chlorine and alkane could react to form alkylhalide and HCl. Both Cl2 and Br2 substitute halogen for hydrogen in compound containingC―H bond. The reactions are initiated by either heat or irradiation with UV light and orvisible light.Fluorination also occurs with alkane but some substitution reaction must be initiated withlight at low temperature.The halogenation reactions of alkane occur via substitution reaction. Note that the order ofreactivity of halogenations with alkane is F > Cl > Br while iodine undergoes little or noreaction. Because each hydrogen is subjected to substitution by a halogen, all possible
3isomeric monohalides are obtained in the halogenation reaction. These isomeric products arebased on the number of equivalent hydrogen positions on the alkane that is undergoing thisreaction.There are three kinds of equivalent hydrogen namely: primary hydrogen (e.g CH3), secondaryhydrogen (e.g CH2) and tertiary hydrogen (e.g CH). It is equally important to note that thepossible kinds of equivalent hydrogen can as well be used to determine the possible numberof isomers that a particular alkane can have.For instance, fluorination of n-butane in the presence of UV light at low temperature givesthe following isomeric product.UV (-800C)CH3CH2CH2CH3 + F2 ――――→ CH2CH2CH2CH3 + CH3CHCH2CH3 + HFLow temp. │ (60% yield) │ (40% yield)F FThe isomeric halides obtained from different equivalent hydrogen position are oftenseparated by fractional distillation using an efficient distillation column and a highrefluxation within the column.It has been observed experimentally that isomeric halides obtained do not correspond directlyto the relative number of chemically equivalent hydrogen at each chemically differentposition.For instance in the chlorination of propane in the presence of UV light at 3000C gave thefollowing isomeric and percentage yields.CH3CH2CH3 + Cl2 ――→ CH2CH2CH3 + CH3CHCH3│ │Cl ClPropane has six equivalent primary positions and only two equivalent secondary positions, ifchlorination was purely statistical, one would expect a ratio of 75% to 25%, but what isobserved experimentally is a ratio of 50% to 50%.
4Relative Reactivity in the Halogenation of AlkaneHalogenation of alkane as earlier discussed does not give the isomeric primary, secondaryand tertiary monohalide in statistical yield. The observed ratio of the product indicates adifference in the reactivities of primary, secondary and tertiary positions. The ratio of theobserved yield to the predicted yield of 2-chloro propane divided by the ratio the observed tothe predicted yield of 1-chloro propane represent the difference in reactivity for chlorinationat secondary positions compared to the primary position. This ratio is called relativereactivity (R.R).This relative reactivity of 3.0 indicates that hydrogen in the secondary position of propane are3 times more reactive than are the hydrogens of the primary positions towards chlorination at3000C.Equally a hydrogen on a tertiary hydrogen position is 4.5 time more reactive towardchlorination at 3000C than a hydrogen at primary position.In summary, the relative reactivities of hydrogen toward chlorination at 3000C follow theorder 30> 20> 10
5All chlorination reactions performed in the gas phase at 3000C have the same order of relativereactivity.Mechanism of Halogenation Reaction of AlkaneCH4 + Cl2 ―→ CH3Cl +HCl Chain Initiation stepUVCl2 ―→ Cl.+Cl.UVCH4 ―→ CH3.+ H. Chain Propagating stepCl.+ CH4 ―→ CH3.+ HClCH3 + Cl2 ―→ CH3―Cl + Cl. Chain terminating StageCl.+ Cl.―→ Cl2CH3.+ H.―→ CH4The free radical mechanism for halogenation reactions are in three steps and it occur in chaingenerally called Free Radical Reaction Chain Mechanism.It begins with an initiation step which involves cleavage of the weakest covalent bond in thesystem to form radicals. Radicals are species formed through homolytical process.
6The association of a small portion of initiator molecules start with a sequence of selfpropagating reactions that are known as Propagating step.Chemical Properties of Free RadicalsRadical CouplingCH3.+ CH3.―→ CH3. .CH3 → CH3―CH3Abstraction of AtomCH3.+ A.―.B → CH3―A + B.Radical AdditionCH3.+ H2C = CH2 → CH3.+ CH2.―.CH2 → CH3― CH2 ― CH2.Bond Dissociation Energy and Free RadicalsFree radicals are formed through homolytical cleavage of covalent bond. Energy required forthe homolytic cleavage of two atoms is known as Bond Dissociation Energy [BDE].The lower the BDE, the less the energy required to form homolytic cleavage. For instance,less energy is required to form Br―Br bond which is 46Kcal/mol than Cl―Cl bond which is58Kcal/mol. Equally more energy is required to break or cleave C―H bond in methanewhich is 102Kcal/mol than in C2H6 which is 97Kcal/mol.Application of Bond Dissociation Energy [BDE]Bond Dissociation Energy [BDE] allows us to estimate the possibility of the pathway bywhich certain chemical reaction occur. For instance in the chlorination of methane to formchloro methane and hydrogen chloride.
7CH4 + Cl2 ―→ CH3Cl +HClThe BDE value enables us to know which bond is broken first or preferentially.E.g. UVCl2 ―→ Cl.+Cl.UVCH4 ―→ CH3.+ H.BDE also allows a prediction of the probability of subsequent reaction pathway. E.g. reactionof chlorine atom or radicals.Cl.+ CH4 ―→ CH3.+ HClSince BDE is characterised by the release of energy, hence reaction of chlorine radical withpropane is exothermic. This is shown below:CH3CH2CH3 + Cl.→ CH3CH2CH2.+ HClBond broken = CH3CH2CH2―H, BDE = 97Kcal/molBond formed = H―Cl, BDE = 103Kcal/mol∆H = ΣBDE(Bond broken) - ΣBDE(Bond formed)∆H = 97-103∆H = -6Kcal/molRelative Stability of RadicalsThe order of radical stability follows the order of relative reactivity in the halogenation ofalkane. For instance hydrogen abstraction from a tertiary position is favoured over that ofprimary position.
8Hence tertiary alkyl radical is more stable than secondary alkyl radical. Likewise, formationof a secondary alkyl radical by hydrogen abstraction from a secondary position is favouredover formation of the less stable primary radical by hydrogen abstraction in the primaryposition.Equally it has been experimentally observed that the more resonance structure that can bewritten, the more stable the radical is. 30> 20> 10Also, note that phenyl radical is more stable than ethyl radical, due to the presence of moredouble bonds.STEREOCHEMISTRYStereochemistry is a sub discipline of chemistry that involves the study of the relative spatialarrangement of atoms that form the structure of molecules. Stereochemistry also known as 3dimensionality chemistry focuses on stereo isomers and spans the entire spectrum of organic,inorganic, biological, physical and especially supra molecular chemistry.Stereo isomers are compounds with the same chemical formula but which have different 3-dimensional structures because of the different ways the atoms of the molecule are arrangedor oriented in space.Enantiomers are stereo isomers which are not super imposable on a mirror image. They areoptically active.Stereo chemistry on Tetrahedral CarbonStereochemistry refers to the arrangement in space of atoms of organic compounds. Thehands are not identical, they are mirror images. For instance compound CHXYZ cannot be
9super imposed on its mirror image and it represent a special kind of stereo isomer calledEnantiomer.Enantiomer is from the greek word ‘enantio’ meaning opposite. Enantiomers are related toeach other just as right hand is related to left hand. It results whenever a tetrahedral carbon isbonded to four different substituents.For example, 2-hydroxyl propanoic acid also called Lactic acid.H │ H│ │ │H3C―C―COOH │ HOOC―C―CH3│ │ │OH │ OHMirrorLactic acid has no plane of symmetry and it is chiral, the central carbon is the chiral centre.Compounds that are not identical to their mirror images and thus exist in two enantiometricform are said to be chiral.Chirality is a term that describe the spatial arrangement of atoms that is non-super imposableon its mirror image. Such an object has no symmetry elements of the second kind. If theobject is super imposable on its mirror image, the object is described as being achiral.A plane of symmetry is an imaginary line that cut through an object or molecule, so that one-half of the object is an exact mirror images of the exact other half.POLY FUNCTIONAL CHEMISTRYAmino acids are the building blocks of life molecules called PROTEIN. All amino acids existas α-amino acids. α-amino acids are naturally occurring carboxylic acids with an amino groupattached to the α-carbon atom [carbon containing COOH]
10General formula of amino acid is shown below:H│R―C―COOH│NH2Where R can be hydrogen or alkyl group. When R is hydrogen, we have glycine.H│H―C―COOH│NH2Amino as a baseAction with acid such as HClH H│ │H―C―COOH + HCl → H―C―COOH│ │NH2 NH2 (Glycine hydrochloride salt)Acetylation of GlycineH H│ │H―C―COOH + CH3COCl → CH3CO―N―C―COOH│ │ │NH2 H NH2 (N-acetylglycine)Action with Nitrous acidH H│ │H―C―COOH + HNO2→ H―C―COOH│ │NH2 OH (Hydroxyl acetic acid)Amino as an AcidAction with BaseH H
11│ │H―C―COOH + NaOH→ H―C―COONa + H2O│ │NH2 NH2 (Sodium glycine)Action with EthanolH H│ │H―C―COOH + CH3CH2OH→ H―C―COOCH2CH3│ │NH2 NH2 (Ethyl glycine)Amino Acid as both Acid and BaseIt forms internal saltH H│ │H―C―COOH ↔ H―C―COO-│ │NH2 NH3 (Zwitter ion)Formation of AmidesAmino acids form both cyclic and linear amides with themselves.NH2 HOCO NH―CO Heat ⁄ H―C―H + C―H ――→ H―C―H H―C―H + 2H2OCOOH H NH2 CO―NHAmide is the carbanide of amineH H H│ │ │H―C―CO―OH + H―NH― C ―CO―OH + H―NH―C―COOH│ │ │NH2 H H││˅H H H│ │ │H―C―CO ―NH― C ―CO― NH―C―COOH│ │ │NH2 H HThe linear amide is called peptides which lead to the formation of proteins.
12AROMATICITYAromatic compounds are compounds containing benzene ring or closely related ring. Thesecompounds are cyclic generally containing 5, 6 or 7 membered rings. Aromaticity impliesthat the Pi-electrons are delocalized over the entire ring system and they are stabilized by thepie-electron delocalization called RESONANCE. For instance, Benzene is represented by theKekule structure.Properties of Aromatic CompoundsThey undergo substitution reaction rather than addition reaction with polar reagentssuch as HNO3, H2SO4 and Br2. The unsaturated bonds in the ring are preserved in thisreaction.They posses unique NMR spectra.They are resistant to oxidation by aqueous potassium permanganate or nitric acid.Thermal stability: The heat of hydrogenation and combustion is usually less thanexpected.They obey Huckel’s (4n+2) electrons rule, where n = number of rings.They are flat or near flat moleculesThey are cyclic, cloud of de-localised electrons are above and below the plain ofthe molecules.Resonance Structure of BenzeneBenzene- a colourless compound with boiling point of 80oC was first isolated by MichaelFaraday in1825 from the oily residue collected in the Illumin along gas lines of London. Themolecular formula of benzene is C6H6, which suggest that benzene is an unsaturatedhydrocarbon. Thus, chemists believe that it should be able to undergo electrovalent additionreaction such as hydrogenation, halogenations and reaction with halogen acids. Benzene is ahybrid of two equal energy (Kekule) structures, differing only in the location of the double
13bond. In the structure of Benzene, the six bond angles are equal (1200), hybridization is sp2and planar from x-ray analysis. The bonding in benzene is a multicenter bonding ordelocalized bonding. The pie ( ) electrons in the benzene is delocalized and not restricted toeither multicenter bonding or delocalized bonding on any carbon atom.Benzene is a molecule with high pie ( ) electron density and so electrophilic reaction isexpected.The two canonical forms exist. The implication of the parameter highlighted above is anindication that the double bonds in benzene are unlike that found in alkene. Also experimenthas shown that benzene does not undergo addition reaction, expected in the C=C double bondin alkene. For comparison, a saturated alkane of six carbon atoms has the molecular formulaC6H14 and saturated cycloalkane of six carbon atom has molecular formula of C6H12 whilebenzene has a molecular formula of C6H6. Considering benzene’s high degree ofunsaturation, it is expected that it will be highly reactive and to exhibit reactionscharacteristics of alkenes and alkynes. However, this is not so, as benzene does not undergoaddition, oxidation and reduction reactions, characteristics of alkenes and alkynes. For
14instance, it does not decolorizes bromine water, nor oxidized by potassium per manganate(KMnO4) or Chromic acid (CrO3) under conditions that readily oxidizes alkenes and alkynes.Rather, benzene undergoes substitution reaction just like alkanes.Structures of BenzeneKekule’s model;In 1865, Kekule a London chemist worked seriously on the structure of Benzene. Heproposed that the six carbon atoms of benzene are arranged in a six membered ring withhydrogen attached to each carbon. To maintain the then established tetravalency of carbon,Kekule further proposed that the ring contains three double bonds that shift back and forth sorapidly that the two forms cannot be separated. The model above is called Kekule’s structure.The Kekule’s structure was found to be consistent with many experimental observations.Bonding in BenzeneEach carbon atom is sp2 hybridized and its sigma bonded to two other carbon atoms and onehydrogen atom. These sigma bonds comprised the skeleton of the molecule. Each carbonatom has one electron in a p-orbital at right angle to the plane of the ring. These p-orbitalsoverlap equally with each of the two adjacent p-orbital to form a pie-electron system parallelto, above and below the plane of the ring. The six -electrons are associated with six carbonatoms. They are therefore more delocalized and this accounts for the great stability and largeresonance energy of aromatic rings.Calculating the Resonance EnergyThe observed heat of combustion of benzene is -3301.6KJ/mol. Theoretical values arecalculated for C6H6 by adding the contributions from each bond obtained experimentally forother compounds. E.g C=C is -492.5KJ/mol, C-C is -206.3KJ/mol and -225.9KJ/mol for C-H.These data can be used to calculate the heat of combustion for benzene. The difference
15between this value and the experimental value gives the resonance energy. For example, inbenzene, there are; 6 C-H bonds, 3 C-C bonds, 3 C=C bonds.6 C-C bonds = (6x -225.9) KJ/mol = -1355.4KJ/mol3 C-C bonds = (3x -206.3) KJ/mol = - 618.9 KJ/mol3 C=C bonds = (3x -492.5) KJ/mol = -1477.5KJ/molCalculated value = Total ΔHc = -3451.8KJ/molExperimental value = - 3301.6KJ/molDifference = 150.2KJ/molThis difference is the resonance energy of benzene. Hence, the resonance energy is150.2KJ/mol.For an organic compound to be aromatic, it must be cyclic, planar, possess delocalized pie-electrons and obey Huckel’s rule of 4n+2= Π –electrons.Aromaticity and Huckel’s ruleHuckel’s rule (1931) for aromaticity states that if the number of pie-electrons is equal to4n+2, where n equals the number of rings, the compound is aromatic. This rule applies to C-containing monocyclic ring in which each carbon is capable of being sp2 hybridized toprovide a p-orbital for extended pie-bonding. The rule has been extended to unsaturatedheterocyclic compounds and fused ring compounds.ELECTROPHILIC AND NUCLEOPHILIC SUBSTITUTION REACTIONElectrophilic substitution reactions are chemical reactions in which an electrophile displacesa group in a compound. Electrophilic aromatic substitution is characteristic of aromaticcompounds and is an important way of introducing functional groups onto benzene rings.The other main reaction type is electrophilic aliphatic substitution.Electrophilic Aromatic Substitution
16In electrophilic substitution in aromatic compounds, an atom appended to the aromatic ring,usually hydrogen, is replaced by an electrophile. The most important reactions of this typethat take place are aromatic nitration, aromatic halogenation, aromatic sulfonation andacylation and alkylating Friedel-Crafts reactions.Electrophilic Aliphatic SubstitutionIn electrophilic substitution in aliphatic compounds, an electrophile displaces a functionalgroup. This reaction is similar to nucleophilic aliphatic substitution where the reactant is anucleophile rather than an electrophile. The two electrophilic reaction mechanisms, SE1 andSE2 (Substitution Electrophilic), are also similar to the nucleophile counterparts SN1 and SN2.In the SE1 course of action the substrate first ionizes into a carbanion and a positively chargedorganic residue. The carbanion then quickly recombines with the electrophile. The SE2reaction mechanism has a single transition state in which the old bond and the newly formedbond are both present.Electrophilic aliphatic substitution reactions are:NitrosationKetone halogenationKeto-enol tautomerismaliphatic diazonium couplingcarbene insertion into C-H bondsMechanism of Electrophilic Substitution Reaction in Benzene
17Resonance hybrid:In order to restore the resonance structure of benzene ring, a proton (H+) is expelled by abase (Y-) rather than addition of a nucleophile (as in alkene).Electrophilic substitution reaction involves 2 steps:a. Electrophilic attack on the benzene ring by an electrophile leads to the formation of acarbonium ion. The positive charge of this carbonium ion is distributed over the wholemolecule, particularly on the first and third carbon position relative to the carbon atombearing the electrophile.b. The expulsion of an H+from the carbonium ion leads to the formation of a substitutedbenzene.
18Electrophilic Substitution Reaction in Benzene1. NitrationThis is the attachment of nitrogen dioxide (NO2) to the benzene. The equal mixture ofconcentrated sulphuric acid and nitric acid at 550-600C generates nitronium ions (NO2+).The Reaction: HNO3 + H2SO4 → NO2+ + H3O+ + 2HSO4Mechanism of Nitration2. SulphonationThis is the introduction of sulphuric acid group (SO3H) to benzene. Concentrated sulphuricacid containing sulphur trioxide is added to the benzene.Stage 1: Generation of electrophile:2H2SO4 ↔ SO3-+ H3O+ + HSO4-Stage 2: Formation of Hydride
193. HalogenationThis is the introduction of halogen to benzene for halogenations.Benzene Chlorination4. Friedal – Craft AlkylationThis the reaction of benzene with alkyl halides (RCl) to form alkyl benzene or arene in hepresence of AlCl3 as catalyst5. Friedal – Craft AcylationThis is the reaction of benzene with acyl halide or alkanol halide with anhydrous AlCl3 as acatalyst.
20Nucleophilic Substitution ReactionsNucleophilic substitution reaction is an important class of reactions that allow theinterconversion of functional groups, for example R-OH to R-Br. It is a fundamental class ofreaction in which an electron, nucleophile selectively bonds with or attacks the positive orpartially positive charge of an atom or a group of atoms called the leaving group; the positiveor partially positive atom is referred to as an electrophile. The most general form for thereaction may be given as:Nu: + R-LG → R-Nu + LG:The electron pair (:) from the nucleophile (Nu) attacks the substrate (R-LG) forming a newbond, while the leaving group (LG) departs with an electron pair (LG:). The principal productin this case is R-Nu. The nucleophile may be electrically neutral or negatively charged,whereas the substrate is typically neutral or positively charged.An example of nucleophilic substitution is the hydrolysis of an alkyl bromide, R-Br, underalkaline conditions, where the attacking nucleophile is the OH−and the leaving group is Br-.R-Br + OH−→ R-OH + Br−
21Nucleophilic substitution reactions are commonplace in organic chemistry, and they can bebroadly categorised as taking place at a saturated aliphatic carbon or at (less often) a saturatedaromatic or other unsaturated carbon centre.Nucleophilic Substitution at Saturated Carbon CentresA nucleophile (Nu) is the electron rich specie that will react with an electron poor species.There are two fundamental mechanisms in these substitution reactions, depending on therelative timing of these events. They include:Bond breaking from the leaving group to form a carbocation (SN1 reaction)Simultaneous bond formation to the nucleophile and bond breaking (SN2 reaction)S stands for chemical substitution, N stands for nucleophilic, and the number represents thekinetic order of the reaction.SN1 MechanismSN1 indicates a substitution, nucleophilic, unimolecular reaction, described by the expressionrate = k [R-LG]This pathway is a multi-step process with the following characteristics:Step 1: Rate determining (slow) loss of the leaving group, LG, to generate a carbocationintermediate, thenStep 2: Rapid attack of a nucleophile on the electrophilic carbocation to form a new bondSN2 MechanismIn the SN2 reaction mechanism, the addition of the nucleophile and the elimination of leavinggroup take place simultaneously. SN2 occurs where the central carbon atom is easilyaccessible to the nucleophile. By contrast the SN1 reaction involves two steps. SN1 reactions
22tend to be important when the central carbon atom of the substrate is surrounded by bulkygroups, both because such groups interfere sterically with the SN2 reaction and because ahighly substituted carbon forms a stable carbocation.Nucleophilic substitution reactionsThere are many reactions in organic chemistry that involve this type of mechanism. Commonexamples includeOrganic reductions with hydrides, for exampleR-X → R-H using LiAlH4 (SN2)Hydrolysis reactions such asR-Br + OH−→ R-OH + Br−(SN2) orR-Br + H2O → R-OH + HBr (SN1)Williamson ether synthesisR-Br + OR−→ R-OR + Br−(SN2)Nucleophilic Substitution at Unsaturated Carbon CentresNucleophilic substitution via the SN1 or SN2 mechanism does not generally occur with vinylor aryl halides or related compounds. Under certain conditions nucleophilic substitutions mayoccur, via other mechanisms such as those described in the nucleophilic aromatic substitutionarticle.When the substitution occurs at the carbonyl group, the acyl group may undergo nucleophilicacyl substitution. This is the normal mode of substitution with carboxylic acid derivativessuch as acyl chlorides, esters and amides.Physical Properties of Organic CompoundsAn organic compound is any member of a large class of gaseous, liquid, or solid chemicalcompounds whose molecules contain carbon. Chemically, most organic compounds can be
23divided among hydrocarbons, oxygen-containing compounds, nitrogen-containingcompounds, sulfur-containing compounds, organohalides, phosphorus-containingcompounds, or combinations of these kinds of compounds. Virtually all organic compoundscontain hydrogen and have at least one C–H bond. The simplest organic compounds andthose easiest to understand, are those that contain only hydrogen and carbon, they are calledHYDROCARBONS They are used to illustrate some of the most fundamental points oforganic chemistry, including organic formulas, structures, and names.The three-dimensional shape of a molecule, that is, its molecular geometry, is particularlyimportant in organic chemistry. This is because it’s molecular geometry determines, in part,the properties of an organic molecule, particularly its interactions with biological systems andhow it is metabolized by organisms.The physical properties of organic compounds include the following: melting point, boilingpoint, density, formula and refractive index.One of the most revealing of all physical properties for a chemical substance is its boilingpoint. Boiling point reflects the strength of the intermolecular attractive forces that hold themolecules of a substance together in a condensed phase, and as such, it is useful to comparethe boiling points for related compounds to see how structural differences account for thedifferences in intermolecular attractions. After briefly reviewing the nature of intermolecularattractive forces, this page will examine trends in boiling points for various groups ofcompounds to help the reader understand how size, shape, and functional group polarityaffect boiling point.
24ReferencesBola O; Wole, F. and Jide, A. 2003Basic Organic Chemistry, Panaf Publishing, Inc.Clayden, G., Waren and Wothers, 2000. Organic Chemistry, Oxford UniversityPress.Manaham, S. E. 2001. Fundamentalsof Environmental Chemistry. Second Edition, 396-406Boca Raton CRC Press LLC