Pharmaceutical Organic Chemistry I PHC 102 PDF

Pharmaceutical Organic Chemistry I Prof.Dr. Azza Taher  What`s meant by organic chemistry? Chemistry of Carbon [ C ] Compounds. Chemistry of Life [ proteins, amino acids DNA, RNA ,Sugar……]. In Addition to, medicine , dyes, plastics,….etc  Valency Atoms in Organic Chemistry form fi...

Pharmaceutical Organic Chemistry I Prof.Dr. Azza Taher  What`s meant by organic chemistry? Chemistry of Carbon [ C ] Compounds. Chemistry of Life [ proteins, amino acids DNA, RNA ,Sugar……]. In Addition to, medicine , dyes, plastics,….etc  Valency Atoms in Organic Chemistry form fixed number of bonds This number is determined by the number of electrons in the outermost shell  Valency of Carbon Carbon has 2 electrons in its outermost shell From this it was expected to be……Divalent. Carbon was found to be ……………..Tetravalent  Electronegativity (EN): This is the tendency or the ability of an atom to attract electrons. Especially electron present in the outermost shell(valence or bonding electron). EN increases in the same period (horizontal row) of the periodic table with the increase in the atomic number (left to right) and decreases as we go down in the vertical column (group). Valence electron Nucleus 5  Electronegativity measures the ability of an atom to attract electrons Electronegativities of Selected Elements H 2.2 Li Be B C N O F 1.0 1.6 2.0 2.6 3.0 3.4 4.0 Na Mg Al Si P S Cl 0.9 1.3 1.6 1.9 2.2 2.6 3.2 K Br 0.8 3.0 I 2.7 8 increasing increasing 9 Types of Chemical Bonds Ionic bond Covalent bond H-bond  Ionic Bond Formed between electro positive element (group 1,2, 3) and electro negative element (group 5, 6, 7) e.g. formed between atoms widely different in EN (> 2) H e.g. Na+Cl- , K Br- + 2.2 Be B C N O F Li 1.6 2.0 2.6 3.0 3.4 4.0 1.0 Mg Al Si P S Cl Na 1.3 1.6 1.9 2.2 2.6 3.2 0.9 Br K 3.0 0.8 I 2.7  Covalent Bond Formed between two equally electronegative elements (group 4, 5, 6, 7) Two types: A] Non-polar covalent C-C , H-H, Cl-Cl [ EN=0] B] Polar covalent + - - + - + C-Li, C- Cl [ EN< C - Cl 2] C - Li C - Mg I  Types of chemical bonds 2- Ionic bond 1- Covalent bonds 1- Covalent bonds A covalent bond is a chemical bond that involves the sharing of electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs and the stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding. 4 A-Nonpolar covalent bond: Nonpolar covalent bonds are a type of chemical bond where two atoms share a pair of electrons equally(no difference in EN ,atom of the same type or very small difference in EN, different type of atom.) in EN with each other. Bonding pair of electrons at equal Distance between the nuclei of the 2 atoms 5 B-Polar covalent bond: Polar covalent bonding is a type of chemical bond where a pair of electrons(bonding electron) is unequally shared between two atoms. In a polar covalent bond, the electrons are not equally shared due to the great difference in EN between the 2 atom forming the bond(diff. in EN < 2). The atom of higher EN attract or withdraw the bonding electron pair closer to it acquiring partial –ve charge(δ- ) Electron rich and the atom that are directly attached to it acquiring partial +ve charge(δ+ ) electron deficient induces polar bond 6  δ+ δ- + - - + - + C - Cl C - Li C - Mg I 7 3) Hydrogen-bonding: this occurs between H atoms bonded to small strongly EN atoms (O, N or F), and unshared electron pair of the electronegative atom. 1-intermolecular H-bonding: take place between 2 or more molecule of the same type or different type and represented by dashed lines. Cyclic dimer of acetic acid; dashed green lines represent hydrogen bonds 8 2-intramolecular H-bonding(Chelation) It take place within one single molecule. 9 The electronic configuration of Carbon atom: Only two electrons can occupy an orbital, and they must be of opposite spin, a statement called the Pauli exclusion principle. Molecular orbitals and covalent bonding: Electronic configuration of carbon suggests that carbon is divalent but actually its tetravalent. HOW ?????? This can be explained according to Hybridization concept.  sp3 Hybridization: Electronic configuration of carbon: 12C6 (1s2, 2s2, 2p2). First step: Second step: Involved hybridaztion between the three 2p atomic orbitals with The 2s atomic orbital to form 4 identical atomic orbitals that is called sp3. sp3 Hybridization of Methane CH4 Carbon atom of methane has 4 equivalent bonds with 4 H atoms Bond angle : 109.5o bond length : 1.09 Ao has tetrahydral configuration. This can be explained by hybridization of the 4 second level atomic orbitals 2s + 2p (2px, 2py, 2pz) to form 4 equivalent molecular orbitals sp3 Sp2 Hybridization: 1. In Sp2 Hybridization, carbon hybridize 2s orbital + two 2p orbital to form 3 sp2 hybridized orbital. 2. 3 sp2 orbitals are planar with bond angle : 120o 3. While the 3rd 2p orbital remains unhybridized ┴ to the formed 3 sp2 hybridized orbital 4. In alkenes, where 2 carbon atoms bonded to each other by double bond. e.g. sp2 hybridization of ethene. * Each of the carbon-hydrogen sigma bonds is formed by overlap of an sp2 hybrid orbital on carbon with the ls orbital of a hydrogen atom. * The remaining sp2 orbitals overlap in the region between the carbon nuclei, providing a sigma bond between the 2 carbon atoms. * The π Bond, formed from side to side overlap of the two unhybridized p orbitals. Sp Hybridization: Occurs in alkynes where carbon attached to only 2 atoms. e.g. acetylene H-C≡C-H In Sp Hybridization carbon hybridize 2s orbital + only one 2p orbital to form two sp hybridized orbital with bond angle : 180o While the 2 unhybridized 2p orbital remains ┴ to the formed two sp hybridized orbital & ┴ to each other. The structure of acetylene: Each carbon is bonded to a hydrogen atom by sp-1s σ bond. The triple bond is formed between two sp hybridized carbon; 1- One sp-sp σ bond. 2- Two π bonds formed from side to side overlapping between the two unhybridized 2p orbitals of one carbon with the two 2p orbitals of the other carbon.  Electron Displacement Exerted by Substituents (G): C G The ability of an atom or group(substituant)(G) to either donate electron to another region in the molecule or to attract electron to itself from the other portion of the molecule inducing permenant polarization. Inductive effect Mesmeric effect 1  1-Inductive effect ( I ) is the redistribution of electron density of bonding pair of electron (uneven sharing) through a traditional sigma bonded structure according to the electronegativity of the atoms involved. The inductive effect drops across every sigma bond involved limiting its effect to only a few bonds.( electronic displacement).(No transfer of electron). 2 The electron cloud in a σ-bond between two unlike atoms is not uniform and is slightly displaced towards the more electronegative of the two atoms. This causes a permanent state of bond polarization, where the more electronegative atom has a slight negative charge (δ–) and the other atom has a slight positive charge (δ+). If the electronegative atom is then joined to a chain of atoms, usually carbon, the positive charge is relayed to the other atoms in the chain. This is the electron-withdrawing inductive effect, also known as the effect. Some groups, such as the alkyl group, are less electron-withdrawing than hydrogen and are therefore considered as electron-releasing. This is electron releasing character and is indicated by the effect. In short, alkyl groups tend to give electrons, leading to induction effect. 3 Inductive effect (I): this is characterized by 1. Electron displacement along the chains via  bond orbitals. 2. The effect becomes less as it proceeds away from the substituent (G), i.e. the effect decreases with the increase in distance from substituent. 3. Undergoes permenant polarization in the molecules. 4. (-I) effect: means electron displacement towards the substituent (G): when G = F, Cl, Br, I, OH, NH2, NO2 (electron withdrawing atom or group) e.g.: δ δ δ+ δ δ+ δ+ δ- 4  5. (+I) effect: means electron displacement away from G: when G = Li , Mg , Cd (electron donating atom or group) e.g δ- δ+ N.B. It should be noted that alkyl group is an electron donating group. has ( +I ) effect and play the most important rule in stability of the carbocation R+. 5 2-Mesomeric effect ( resonance) ( M ): Mesomeric effect is the redistribution of electrons which takes place in unsaturated systems and specially in conjugated systems via their  bond orbitals. i.e accompanied by transfer of electron( electron or lone pair electron) 6  1- bonding to non bonding. Carbonyl group is an example of –M effect. 2- bonding to new bonding. If the carbonyl group is conjugated with C = C bond, the above polarization can be transmitted further via the  - electrons Delocalization takes place, so that an electron deficient atom 7 results at C-5. Difference between I and M I M 1) Electrons move in σ bond 1) Electrons move in π bond 2) Must be difference in EN 2) Not a must 3) Decrease by distance 3) Not affected by distance Types of bond cleavage 1) Homolytic 2) Heterolytic  1)Homolytic Each atom in the covalent bond U.V recieves one electron A..B A. +.B U.V Cl-Cl Cl. + Cl.  Bond cleavage or scission is the splitting of chemical bonds.. In general, there are two classifications for bond cleavage: homolytic and heterolytic, depending on the nature of the process Homolytic bond cleavage (homolytic cleavage; homolysis): Bond breaking in which the bonding electron pair is split evenly (equally) between the products. Homolytic cleavage often produces radicals ( R. Or X. ) 11 In the photolytic bromination of methane, the chain initiation mechanism step is an example of homolytic bond cleavage a-Homolytic cleavage mainly take place in non polar compound Where the bond present between 2 atom with no difference in EN b- a-Homolytic cleavage need initiator to start the reaction Like Ultraviolet (h ) or peroxide ( ROOR) or high temerature 12 2-Heterolytic bond cleavage (heterolytic cleavage; heterolysis): Bond breaking in which the bonding electron pair is split unevenly(uneqally) between the products. Heterolytic cleavage Often produces positively and negatively charged product( R+or R- X+ or X- ) 13 Heterolytic cleavage mainly take place in polar compound where the bond present between 2 atom with difference in EN. Both electrons forming the covalent bond go to one fragment( more electronegative atom). A more EN than B 14 Li has +I effect Cl has -I effect 15  Carbon containing intermediates: 1-A carbocation are positively charged species containing a carbon atom having only 6 electrons in 3 covalent bonds. Carbocation carbon is sp2 hybridized C and its shape is planar. +I effect of R groups stabilizes the carbocations.. Carbocations are generally unstable because they do not have eight electrons to satisfy the octet rule. cation, demonstrating planar geometry and sp2 hybridization 16  3 R group 2 R group 1 R group 3 +I effect(electron release) 2 +I effect(electron release) 1 +I effect(electron release) high neutralization moderate neutralization weake neutralization of the positive charge of the positive charge of the positive charge Low energy content Moderate energy content High energy content High stability moderate stability low stability Order of stability of examples of tertiary (III), secondary (II), and primary (I) 17 alkylcarbenium ions, as well as the methyl cation (far right). 2-A carbanion are negatively charged species containing carbon atom with 3 bonds and unshared pair of electrons(negative charge). Carbanion carbon is sp3 hybridized C and its shape is tetrahedral. +I effect of R group destabilizes the carbanion. 18  Order of stability Why? 3-A Free radical an uncharged molecule (typically highly reactive and short-lived) having an unpaired valency electron. Why? 19 tertiary secondary primary methyl free radical Types of chemical reagents 1] E+ 2] Nu-  Types of chemical reagents 1-Electrophiles (E+): Electrophile is an electron seeking or loving species. Electrophiles may be: a-Positively charged atom or group (having formal charge) e.g. H+ (from acids), X+ (from halogens), carbocations( R+), NO2 (nitronium ion), NO+ (nitrosonium ion) or partially positive charge δ+ CH -CH 3 2 CH 2 CH 2 X 2 2-Nucleophiles (Nü): These are atoms or groups (of high electron density) seeking for center of low electron density. Nucleophiles may be a-negatively charged atom or group (having formal charge) b-neutral molecules having unshared electron pairs. e.g. 3  Electrophiles (E+): Nucleophiles (Nü-): electron seeking or loving species These are atoms or groups seeking for center of low electron density. 1- Positively charged atom or group 1- negatively charged atom or e.g. H+ (from acids), X+ (from group e.g. H- (from LiAlH4), X halogens), carbocations, NO2+ - (I -,Br-, Cl-, F -), OH -, -C≡N (nitronium ion), NO+ (nitrosonium ion). 2- neutral molecules having unshared electron pairs. 2- Neutral molecules with vacant e.g. ROH, NH3 and amines , orbitals e.g. AlCl3, FeCl3, SO3. H2O , H2S. Electrophiles attack the molecule at Nucleophiles attack the carbon of the high electron density carbon low electron density (carbanions). (carbocations). Types of Organic Reactions 1-Substitution. 2- Addition. 3-Elimination  Types of Organic Reactions 1- 6 There are three types of substitution reactions according to the entering group: a- Nucleophilic substitution reaction: ( in polar compound) δ+ δ- The entering group is Nu and the leaving group is Nu 7 Leaving group B- should be of high EN than A b- Electrophilic substitution reaction: ( in polar compound) The entering group is E and the leaving group is E Leaving group B+ should be of lower EN( high electro positivity than A to push the bonding electron toA. 8  Substitution reactions "An atom or group is replaced by another atom or group". There are three types of substitution reactions: a) Nucleophilic Substitution(SN): e.g. CH3I + OH- CH3OH + I- A–B + Y- (Nu) A–Y + B- SN b) Electrophilic Substitution(SE): A – B + Y+ (E+) A–Y+ B+ SE e.g. C6H6 (benzene) + +NO2 C6H5NO2+H+ Nitrobenzene c) Free Radical Substitution: A–B + Y. A–Y +. e.g. CH4 + 2Cl. CH3Cl + HCl 2-Addition reactions(decrease in degree of Unsaturation). are limited to chemical compounds that have multiple bonds, such as molecules with carbon-carbon double bonds (alkenes), or with triple bonds (alkynes). Molecules containing carbon—hetero double bonds like carbonyl (C=O) groups, or imine (C=N) groups, can undergo addition as they too have double bond character. An addition reaction is the opposite of an elimination reaction Where the pi bond of the multiple bond cleaved with formation of 2 new σ bond. 10 Electrophilic addition nucleophilic addition Free radical addition 11 3-Elimination reactions(increase in degree of unsaturation). Is the reverse of the addition reaction , where 2 atoms or groups are removed from 2 σ covalent bond ,one removed as Nu (negatively charged)and the second as E( positively charged). a- α- elimination: Where the 2 atoms or group are removed from one and the same atom and give rise to carbene. 12 b- β- elimination(1,2 or α ,β elimination): Where the 2 atom or group are removed from 2 adjacent atoms one removed as Nu (negatively charged) and the second as E( positively charged). And give rise to Alkene. β α 13 c- γ – elimination(1,3 or α , γ elimination): Where the 2 atom or group are removed from2 atoms separated by one carbon , one removed as Nu (negatively charged) and the second as E( positively charged). And give rise to Cyclic compounds. α γ β 14  3) Elimination reactions (E): This is the reverse of addition reactions, two atoms or groups are removed from one molecule. Elimination may be - , - or -E. Cl Cl +-  E: H - C - Cl + NaOH : C - Cl + NaCl + H2O Cl dichloro carbene   CH3-CH2Cl + NaOH  E: CH = CH2 (most common type)    NaOH  E: CH2 - CH2 CH3-CH2-CH2Cl CH2 Hydrocarbons… Classification Name Hydrocarbons Preparations Reactions Saturated Unsaturated (Alkanes) Alkenes Alkynes Hydrocarbons… Nomenclature Name Trivial Name (common) Preparations Reactions IUPAC Name (International Union of Practical & Applied Chemistry) Counting to Ten in Organic Chemistry  01 = meth Mother  02 = eth Enjoys  03 = prop Peanut  04 = but BUTter  05 = pent PENTagon  06 = hex HEXagon  07 = hept HEPTember (Roman sept is Greek hept)  08 = oct OCTober  09 = non NONember (Roman nov is Greek non)  10 = dec DECember ALKANES 4 Alkanes are the hydrocarbons of aliphatic row. Alkanes are hydrocarbons in which all the bonds are single covalent bonds ( 4 -bonds) in tetrahedral st. and SP3 state of hybridization and bond angle 109.3 Alkanes are called saturated hydrocarbons( of C and H atoms only). Alkanes have main general formula CnH2n+2 ane 5 Homologous series is a series of compounds with the same general formula, usually varying by a single parameter—such as the length of a carbon chain( differ only by the same unit CH2 For unbranched alkanes: the prefix n-(normal) is used to indicate an unbranched chain of carbon atoms. For branched alkanes: the prefix iso indicate a methyl group on the second carbon of the chain. Also, the presence of quaternary carbon atom at one end of the chain is indicated by the prefix neo. 6 Hydrocarbons… Nomenclature: IUPAC Name  Take the suffix ane, naming according to the following table: Alkane Number of Number of Name Name Preparations carbons carbons 1 Methane 7 Heptane Reactions 2 Ethane 8 Octane 3 Propane 9 Nonane 4 Butane 10 Decane 5 Pentane 11 Undecane 6 Hexane 12 Dodecane  CH3 (2 skeletal or chain isomers) CH3CH2CH2CH3 CH3CHCH3 n-butane isobutane CH3 CH3 CH3CH2CH2CH2CH3 CH3CHCH2CH3 CH3CCH3 n-pentane isopentane CH3 neopentane 8 Alkanes - Nomenclature Suffix – Our first functional group is alkane, so the suffix is –ane For later functional groups we will drop the –ane root suffix for others Alkane chain # Carbons Name CH4 1 methane CH3CH3 2 ethane CH3CH2CH3 3 propane CH3CH2CH2CH3 4 butane CH3CH2CH2CH2CH3 5 pentane CH3CH2CH2CH2CH2CH3 6 hexane CH3CH2CH2CH2CH2CH2CH3 7 heptane CH3CH2CH2CH2CH2CH2CH2CH3 8 octane CH3CH2CH2CH2CH2CH2CH2CH2CH3 9 nonane CH3CH2CH2CH2CH2CH2CH2CH2CH2CH3 10 decane CH3CH2CH2CH2CH2CH2CH2CH2CH2CH2CH3 11 undecane CH3CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH3 12 dodecane Classes of carbons and hydrogens: Carbon atoms in alkanes can be classified into: A primary (1O) carbon: is the one that is bonded to only one other carbon. A secondary (2O) carbon: is bonded to two other carbons. A tertiary (3O) carbon: that is bonded to three other carbons. A Quaternary(4O) carbon: it is the carbon bonded to four other carbon atoms. Hydrogens are also referred to as 1O, 2O or 3O 10 hydrogens according to the type of carbon atom they are bonded to. 2- Nomenclature for branched chain alkanes: : IUPAC 11  The Three Basic Parts The name for any organic molecule consists of three basic parts: Prefixes -Parent -Suffix Each part of the name has a purpose.  Basic Part - Suffixes Suffixes on the end of the name of an organic molecule tell you what major family the molecule belongs to The suffix for an alkane is “-ane”  Basic Part – the Parent The “parent” part of the name tells you how many carbons are in the main chain of the molecule The main chain of the molecule is defined for alkanes as being the longest chain in the molecule  the Prefixes Prefixes idicates the location,number and type of the substituents that are attached to the main chain (parent) of the molecule.  The family called alkyl halides does not have a suffix. Some substituents Halides are always named as prefixes. Fluorine F is called “fluoro” Chlorine Cl is called “chloro” Bromine Br is called “bromo” Iodine I is called “iodo” NH2 is called amino NO2 ics called nitro  More Prefixes ALKYL Groups CnH2n+2 minus 1H CnH2n+1- The most common prefixes we have in organic molecules are those little fragments of carbon pieces attached to the main chains. The carbon fragments are called “alkyl groups”. They all end in “-yl” to indicate they are fragments of a bigger molecule. ane → -yl  Alkyl Groups(R) Alkyl groups are named similarly to alkanes, based on the number of carbons in the fragment. A fragment of methane, CH4, would be CH3- This fragment is called “methyl” where “meth” stands for one carbon and “yl” stands for fragment (alkyl group).  Ethyl Groups A two-carbon alkane is called ethane, CH3CH3. The corresponding two-carbon fragment is always CH3CH2-, which is called “ethyl”. 4-ethylheptane is the name for this one.  Propyl Groups There are two possible three-carbon alkyl groups to form from propane, CH3CH2CH3. The straight chain version: CH3CH2CH2- which is called “propyl” or “n-propyl” (where n stands for “normal” or straight-chained)  Isopropyl Groups The other possibility is to form the fragment on the central carbon: CH3CHCH3, which is called “isopropyl”  Butyl Groups There are two possible four-carbon alkyl groups to form from butane, CH3CH2CH2CH3. One possibility is to form the fragment on one of the end carbons: CH3CH2CH2CH2-, which is called “butyl” or “n-butyl”  Sec-Butyl Groups The other possibility is to form the fragment one of the central carbons: CH3CHCH2CH3, which is called “sec-butyl”. [Note that the carbon second from the left only has three bonds – so that’s where its bonding to the main chain]  Isobutyl Groups There are two other possible four-carbon alkyl groups to form from isobutane, (CH3)3CH. One is formed as a fragment on one of the three symmetrical end carbons: (CH3)2CH(CH2)-, which is called “isobutyl”  Tert-butyl Groups The other is formed as a fragment on the one central carbon, (CH3)3C-, which is called “tert-butyl” 1. Choose the longest continous chain of carbon atoms and name it as the parent structure. The longest chain may or may not be written in a straight line. 26 27 2. Number the atoms in the carbon chain to give the first substituent the lowest number. Also note that if there are two chains of equal length, pick the chain with more substituents. In the following example, two different chains in the same alkane have seven C atoms. We circle the longest continuous chain as shown in the diagram on the left, since this results in the greater number of substituents. 30 When two or more substituents are present on the same carbon atom of the chain , use that number twice. 31 32 PREPARATION OF ALKANES 1 I - From Alkenes: By Catalytic Hydrogenation: ( reduction) CH3CH=CH2 + H2  CH3CH2CH3 The addition of hydrogen to alkenes is known as a “hydrogenation” or “reduction”. In this reaction a molecule of hydrogen is added to the alkene molecule at the site of unsaturation i.e. where the double bond is. This is achieved under mild conditions when a catalyst is used to bring about this change. Suitable catalysts for this reaction are : (a) Raney Nickel, (b) Pd on 2 C or (c) Pt on C.This is by far the most important way of generating alkanes and is in many ways the easiest reaction to carry out. II-From Alkyl Halides: A-By Reduction: ( active metal and acids) Most alkyl halides react with zinc and aqueous acid to produce an alkane. In this reaction, zinc acts as a reducing agent and causes the halogen of alkyl halide to be replaced by hydrogen. H3C CH2 Zn / CH3COOH H3C CH2 CH CH3 + ZnBr2 CH2 CH3 3 Br III- From reduction of carbonyl compounds: Reduction of the C=O group to CH2 (deoxygenation) is also possible. This may be achieved by two ways: the Clemmensen reduction and the Wolff-Kishner reduction. The product is the corresponding hydrocarbon. In the Clemmensen reduction, the carbonyl compound is treated with Zinc-amalgum and HCl. These conditions would be suitable for a compound unstable in base but stable in acid. In the Wolff-Kishner reduction, the hydrazone derivatives of aldehydes and ketones undergo decomposition when treated with a strong base at elevated temperature with evolution of nitrogen. The reaction is therefore limited to carbonyl compounds that are stable in base.  Zn/Hg NH2NH2 NH2 CH2 C O C N CH2 + N2 HCl base  PHYSICAL PROPERTIE S 6 Alkanes non-polar or only weakly polar, so dipole-dipole and dipole- induced dipole forces are absent only forces of intermolecular attraction are induced dipole- induced dipole forces (electrostatic attraction) can not hydrogen bond  relatively weak intermolecular forces lower mp/bp; increase with size; decrease with branching At room temperature: C1 – C4 are gases C5 – C17 are liquids > C17 are solids alkanes are water insoluble Boiling points: Boiling point increases as the molecular weigh increase because These lead to more atoms, more electrons, more opportunities for induced dipole-induced dipole forces. Heptane Octane Nonane bp 98°C bp 125°C bp 150°C unbranched alkanes show a regular increase (20-30 C) with increasing molecular weight. Branching, of the alkane chain, 8 however, lowers the boiling point. Unbranched alkane are arranged in zigzag form( less compact) to each other increase the surface area , and thus increase the point of contact increasing the possibilities of intermolecular attraction ,need high E and high boiling point 9 branched molecules are more compact with smaller surface area fewer points of contact with other molecules Octane: bp 125°C 2-Methylheptane: bp 118°C 2,2,3,3-Tetramethylbutane: bp 107°C 10 Solubility Alkanes: non-polar compounds insoluble in water and highly polar solvents soluble in non-polar solvents like benzene, 1,1,1-trichloroethane 11 CHEMICAL PROPERTIE S 12 The only reaction is Free radical substitution reaction Halogenation of alkanes with Cl2 or Br2 They react with Cl2 in the presence of light to replace H’s with Cl’s (not easily controlled) 13  Example Write down the reaction mechanism involved in the chlorination of ethane in the presence of diffuse sunlight. Solution: The reaction mechanism is shown as follows: 1. Chain initiation 2. Chain propagation Solution: 3. Chain termination CH3CH3 + Cl2, hv  CH3CH2-Cl + HCl ethane ethyl chloride CH3CH2CH3 + Cl2, hv  CH3CH2CH2-Cl + CH3CHCH3 propane n-propyl chloride Cl isopropyl chloride 45% 55% gives a mixture of both the possible alkyl halides!  CH3CH2CH2CH3 + Cl2, hv  CH3CH2CH2CH2-Cl 30% n-butane n-butyl chloride + CH3CH2CHCH3 70% Cl sec-butyl chloride bromination Is more selective in attack of 30 hydrogen( substitution occur only on 30 hydrogen) atom and can discriminate among different type of alkanes, the greater the difference between activation energies, the larger the selectivity. 17  CH3 CH3 CH3CHCH3 + Br2, hv  CH3CHCH2-Br