© No part of this publication should be reproduced, stored in a retrieval system, or transmitted in any form or (Written according to Revised Syllabus of University of Mumbai any means, electronic, mechanical, photocopying, recording and/or otherwise without the prior written with effect from the academic year 2017-18) permission of the publisher. First Edition : 1995 Seventh Revised Edition : 2004 Eighth Revised Edition : 2005 Reprint : 2006, 2007, 2009 COLLEGE Ninth Revised Edition : 2010 Tenth Revised Edition : 2012 Eleventh Revised Edition : 2013 Reprint : 2014 Twelfth Revised Edition : 2015 ORGANIC (As per New Syllabus) Thirteenth Edition : 2016 Fourteenth Revised Edition : 2017 (As per New Syllabus) Fifteenth Edition : 2018 Sixteenth Edition : 2019

Published by : Mrs. Meena Pandey for Himalaya Publishing House Pvt. Ltd., S.Y.B.Sc. “Ramdoot”, Dr. Bhalerao Marg, Girgaon, Mumbai - 400 004. Phone: 022-23860170/23863863, Fax: 022-23877178 E-mail: [email protected];Website: www.himpub.com Branch Offices : New Delhi : “Pooja Apartments”, 4-B, Murari Lal Street, Ansari Road, Darya Ganj, New Delhi - 110 002. Phones: 011-23270392, 23278631; Fax: 011-23256286 Nagpur : Kundanlal Chandak Industrial Estate, Ghat Road, R.S. Rao Dr. (Mrs.) Sushil Puniyani Nagpur - 440 018. Phones: 0712-2738731, 3296733; Telefax: 0712-2721215 Vice-Principal & Associate Professor, M.Sc., M.Phil., Ph.D., Bengaluru : Plot No. 91-33, 2nd Main Road, Seshadripuram, Dept. of Chemistry, Rtd. Head, Dept. of Chemistry, Behind Nataraja Theatre, Bengaluru - 560 020. G.N. Khalsa College of Arts, Science & Commerce, K.C. College of Arts, Science and Commerce, Phones: 08041138821, 09379847017, 09379847005 Matunga, Mumbai. Churchgate, Mumbai. Hyderabad : No. 3-4-184, Lingampally, Besides Raghavendra Swamy Matham, Kachiguda, Hyderabad - 500 027. Phones: 040-27560041, 27550139; Mobile: 09390905282 Dr. Tanuja Parulekar Prof. Dr. A.K. Upadhyay Chennai : New No. 48/2, Old No. 28/2,Ground Floor, Sarangapani Street, Associate Professor, M.Sc., M.Phil., Ph.D. T. Nagar, Chennai - 600 017. Mobile: 09380460419 Department of Chemistry, Rtd. Head, Dept. of Chemistry, Pune : “Laksha” Apartment, First Floor, No. 527, Mehunpura, Shaniwarpeth, S.I.W.S. College, Smt. CHM College, (Near Prabhat Theatre), Pune - 411 030. Wadala, Mumbai. Ulhasnagar. Phones: 020-24496323/24496333; Mobile: 09370579333 Lucknow : House No. 731, Shekhupura Colony, Near B.D. Convent School, Vikas Nagar, Aliganj, Lucknow - 226 022. Mobile: 09307501549 Ahmedabad : 114, “SHAIL”, 1st Floor, Opp. Madhu Sudan House, C.G. Road, Navrang Pura, Ahmedabad - 380 009. Phone: 079-26560126; Mobile: 09377088847 Ernakulam : 39/176 (New No. 60/251) 1st Floor, Karikkamuri Road, Ernakulam, Kochi - 682 011, Kerala. Phones: 0484-2378012, 2378016; Mobile: 09344199799 Cuttack : New LIC Colony, Behind Kamala Mandap, Badambadi, Cuttack - 753 012, Odisha. Mobile: 09338746007 Kolkata : 108/4, Beliaghata Main Road, Near ID Hospital, Opp. SBI Bank, Kolkata - 700 010. Phone: 033-32449649; Mobile: 07439040301 DTP by : Rajani Tambe. ISO 9001:2015 CERTIFIED Printed at : Geetanjali Press Pvt. Ltd., Nagpur. On behalf of HPH. PREFACE SYLLABUS

COURSE CODE – USCH301 This book is written according to the revised syllabus prescribed by PAPER I the University of Mumbai for S.Y.B.Sc. class, as per the UGC guidelines. THEORY: 45 LECTURES This syllabus will come into effect from the academic year 2017-18. The book gives a good foundation of the theoretical aspects such as acidity, basicity, tautomerism, resonance, H-bonding, etc. In the earlier SEMESTER - III class, the aliphatic compounds are covered. But in this book, the emphasis is on study of aromatic compounds. The chapter on organometallic 3.1 Reactions and Reactivity of Halogenated Hydrocarbon (4L) compounds has been introduced in the book. 3.1.1 Alkyl Halides Several reaction mechanisms have been included in which electron Nucleophilic substitution reactions: SN1, SN2 and SNi shifts have been clearly shown by curved arrows. An introduction has mechanisms with stereochemical aspects and factors been made about simple heterocyclic compounds. Throughout the book affecting nucleophilic substitution reactions-nature of IUPAC names have been given along with the trivial names. Further, substrate, , nucleophilic reagent and leaving group. reactions involving interconversions of compounds are included. 3.1.2 Aryl Halides In the book several charts, tables, P.E. diagrams and illustrations are Reactivity of aryl halides towards nucleophilic substitution given to make the concepts clear. Many questions and excercises have reactions. Nucleophilic aromatic substitution (SNAr) been given for the students to practice. Any suggestions for improvement addition-elimination mechanism and benzyne mechanism. of this edition from teachers as well as students will be highly appreciated. 3.1.2. Organomagnesium and Organolithium Compounds We thank the publisher for bringing out fine edition of this book. (3L) AUTHORS Nomenclature, nature, type and reactivity of carbon-metal bond. Preparation using alkyl/aryl halide. Structure, stability and reactions with compounds containing acidic

hydrogen, carbonyl compounds, CO2, cyanides and epoxides. 3.2 , Phenols and Epoxides (8L) 3.2.1. Alcohols Nomenclature, preparation: Hydration of alkenes, hydrolysis of alkyl halides, reduction of aldehydes and ketones, using Grignard reagent. Properties: Hydrogen bonding, types and effect of hydrogen bonding on different properties. Acidity of alcohols, Reactions of alcohols. (v) (vi) 3.2.2. Phenols COURSE CODE – USCH401 Preparation, physical properties and acidic character. PAPER I Comparative acidic strengths of alcohols and phenols, resonance stabilization of phenoxide . Reactions of phenols. SEMESTER - IV 3.2.3. Epoxides Nomenclature, methods of preparation and reactions of 3.1 Carboxylic Acids and their Derivatives (11L) epoxides: reactivity, ring opening reactions by 3.1.1. Nomenclature, structure and physical properties, acidity (a) In acidic conditions: hydrolysis, reaction with halogen of carboxylic acids, effects of substituents on acid strength halide, , hydrogen cyanide. (b) In neutral or basic of aliphatic and aromatic carboxylic acids. conditions: ammonia, amines, Grignard reagents, alkoxides. 3.1.2. Preparation of carboxylic acids: oxidation of alcohols and alkyl benzene, carbonation of Grignard and hydrolysis of nitriles. PAPER II 3.1.3. Reactions: acidity, salt formation, decarboxylation,

reduction of carboxylic acids with LiAlH4, diborane, Hell- Volhard-Zelinsky reaction, conversion of carboxylic acid Carbonyl Compounds (15L) to acid chlorides, esters, amides and acid anhydrides and 3.1 Nomenclature of aliphatic, alicyclic and aromatic carbonyl their relative reactivity. compounds. Structure, reactivity of aldehydes and ketones and 3.1.4. Mechanism of nucleophilic acyl substitution and acid- methods of preparation; oxidation of primary and secondary catalysed nucleophilic acyl substitution. Interconversion alcohols using PCC, hydration of alkynes, action of Grignard of acid derivatives by nucleophilic acyl substitution. reagent on esters, Rosenmund reduction, Gattermann - Koch formylation and Friedel Craft acylation of arenes. 3.1.5. Mechanism of Claisen condensation and Dieckmann condensation. 3.2 General mechanism of , and acid catalyzed nucleophilic addition reactions. 3.2 Sulphonic acids (4L) Nomenclature, preparation of aromatic sulphonic acids by 3.3 Reactions of aldehydes and ketones with NaHSO3, HCN, RMgX, alcohol, amine, phenyl hydrazine, 2,4-Dinitrophenyl hydrazine, sulphonation of benzene (with mechanism), toluene and LiAlH and NaBH . naphthalene; Reactions: Acidity of arene sulfonic acid, 4 4 comparative acidity of carboxylic acid and sulfonic acids. Salt 3.4 Mechanisms of following reactions: Benzoin condensation, formation, desulphonation. Reaction with alcohol, phosphorous Knoevenagel condensation, Claisen-Schmidt and Cannizzaro pentachloride, IPSO substitution. reaction. PAPER II 3.5 Keto-enol tautomerism: Mechanism of acid and base catalysed enolization Nitrogen containing compounds and heterocyclic compounds 3.6 Active methylene compounds: Acetylacetone, ethyl acetoacetate 3.1 Amines: (4L) diethyl malonate, stabilised enols. Reactions of acetylacetone and Nomenclature, effect of substituent on basicity of aliphatic and ethyl acetoacetate (alkylation, conversion to ketone, mono- and aromatic amines; Preparation: Reduction of aromatic nitro dicarboxylic acid). compounds using catalytic hydrogenation, chemical reduction using Fe-HCl, Sn-HCl, Zn-acetic acid, reduction of nitriles, (vii) (viii) ammonolysis of halides, reductive amination, Hofmann CONTENTS bromamide reaction. Reactions: Salt Formation, N-acylation, N-alkylation, Hofmann’s exhaustive methylation (HEM), Hofmann-, reaction with nitrous acid, carbylamine reaction, Electrophilic substitution in aromatic amines: bromination, nitration and SEMESTER III sulphonation. 3.2 Diazonium Salts: (3L) Paper Unit Chapter Name of Topic No. of Page No. Lectures Preparation and their reactions/synthetic application: Sandmeyer reaction, Gattermann reaction, Gomberg reaction, replacement of I 3.1 – Reactions and Reactivity of 7 diazo group by –H, –OH. Azo coupling with phenols, naphthols Halogenated Hydrocarbons and aromatic amines, reduction of diazonium salt to aryl hydrazine 3.1.1 1 Alkyl Halides 3 – 14 and hydroazobenzene. 3.1.2 2 Aryl Halides 15 – 23 3.3 Heterocyclic Compounds: (8L) 3.1.3 3 Organomagnesium and 24 – 41 3.3.1. Classification, nomenclature, electronic structure, Organolithium Compounds aromaticity in 5-numbered and 6-membered rings 3.2 – Alcohols, Phenols, Epoxides 8 containing one heteroatom. 3.2.1 4 Alcohols 42 – 64 3.3.2. Synthesis of Furan, Pyrrole (Paal-Knorr synthesis, Knorr 3.2.2 5 Phenols 65 – 86 pyrrole synthesis, and Hantzsch synthesis), Thiophene, 3.2.3 6 Epoxides 87 – 95 (Hantzsch synthesis). II 3.1 7 Carbonyl Compounds 15 96 – 137 3.3.3. Reactivity of furan, pyrrole and thiophene towards electrophilic substitution reactions on the basis of stability SEMESTER IV of intermediate and of pyridine on the basis of electron I 3.1 8 Carboxylic Acids and their 11 141 – 172 distribution. Reactivity of pyridine towards nucleophilic Derivatives substitution on the basis of electron distribution. 3.2 9 Sulphonic Acids 4 173 – 182 3.3.4. Reactions of furan, pyrrole and thiophene: halogenation, nitration, sulphonation, Vilsmeier-Haack reaction, Friedel- II 3.1 10 Amines 5 183 – 206 Crafts reaction. Furan: Diels-Alder reaction, ring opening. 3.2 11 Diazonium Salts 2 207 – 218 Pyrrole: Acidity and basicity of pyrrole. Comparison of 3.3 12 Heterocyclic Compounds 8 219 – 240 basicity of pyrrole and pyrrolidine. 3.3.5. Pyridine: Basicity. Comparison of basicity of pyridine, pyrrole and piperidine. Sulphonation of pyridine (with and without catalyst), reduction and action of sodamide (Chichibabin reaction). SEMESTER - III Alkyl Halides 4 College Organic Chemistry – S.Y.B.Sc. 3.1 Reactions and Reactivity of Halogenated Kinetics of the reaction: Experimentally it is observed that the rate of reaction depends on the concentrations of both CH Br and :OH– . Hydrocarbons 3 – Rate = k [CH3Br] [OH ] 2 CHAPTER 1 Therefore, it is a second order nucleophilic or SN reaction. Mechanism of Hydrolysis: This is a one step reaction whose mechanism UNIT 3.1.1 is explained as follows.

H H H + Slow + Rapid Alkyl Halides HO + C Br HO ---- C ---- Br HO C + Br H H H H H H Transition state Inversion of configuration The C Br bond is polar. The nucleophile OH– is repelled by the halogen Nucleophilic substitutions in Alkyl halides: atom having fractional negative charge. Therefore, the nucleophile, i.e., the When a substitution is brought about by a nucleophile it is called OH– group approaches the carbon atom from the backside, i.e., the side opposite nucleophilic substitution or SN reaction. to the group to be substituted (Br). The formation of C OH bond and breakage The number of molecules taking part in a as represented of C Br bond takes place simultaneously. Therefore, a transition state is by a simple chemical equation is called . Thus the reactions can formed in which both OH and Br are loosely attached and negative charge is be classified as uni or mono molecular, bimolecular, ter-molecular etc. However, evenly distributed between them. In this state the molecule has highest energy the number of molecules whose concentration actually affects the rate of the content as five groups are attached to the central carbon atom. Therefore, the reaction is called order of the reaction. The SN reactions are further classified transition state represents a highly unstable arrangement and very rapidly – as SN1 and SN2 in which the order of the reaction is 1 and 2 respectively. eliminates :Br ion to give the product. (i) Mechanism of SN2 reaction (Substitution Nucleophilic The other three H-atoms attached to the central carbon atom move through Bimoleculer) a coplanar configuration in the transition state. Due to the backside attack of nucleophile the product is formed with inversion of configuration, i.e., the Example: Mechanism of alkaline hydrolysis of primary alkyl halide: product has exactly the opposite configuration as compared to the substrate. Consider the action of aqueous sodium or potassium on a Energy profile diagram: It is a graph of potential energy changes taking primary alkyl halide such as methyl bromide. place during the course of the reaction plotted against the reaction co-ordinates. CH3Br + NaOH CH3OH + NaBr In the ionic form the above equation can be written as: – – CH3Br + OH CH3OH + Br During the hydrolysis a stronger (more basic) nucleophile namely :OH– ions displaces or substitutes the weaker nucleophile, Br– ions. Therefore, the reaction is a nucleophilic substitution reaction (SN reaction).

— 3 — Alkyl Halides 5 6 College Organic Chemistry – S.Y.B.Sc.

Mechanism: SN2 reaction occurs in one step. The nucleophile ( OH H ion) attacks the carbon from the side opposite to the leaving group (bromine). HO ----- C -----Br (Transition state) In the transition state, the carbon atom is partially bonded to both –OH and –Br. The other three groups and carbon atom become coplanar. When C–O H H bond is completely formed, at the same time C–Br bond is completely broken. The overall reaction is a concerted process occuring in one step without any Ea = Energy of activation y intermediate. Hence, in their final product, the entering group occupies a g

r H = Heat of reaction e Ea position different from the leaving group and thus causing inversion of n

e configuration in the product. l a i t n

e C6H13 C H t CH 6 13 CH3 Br + :OH 6 13 – o OH – – –:Br

P H Reactants C Br HO C Br HO C H H CH3 OH + :Br H CH3 Product H3C CH3 Reaction co-ordinates (–) 2-Bromooctane T.S (+) Octan-2-ol Fig. 1.1 Energy profile diagram of alkaline hydrolysis of methyl bromide by SN2 mechanism. Therefore, SN2 reactions proceed with stereochemical inversion called Walden inversions. Thus, every SN2 reaction at a chiral carbon atom results in 100% inversion For example, chlorosuccinic acid and malic acid can be interconverted 2 of configuration. The reaction with the reagents NaOH, PCl5, etc. follow SN by nucleophilic substitutions. mechanism and hence cause inversion of configuration. However, reaction with AgOH does not cause inversion. COOH COOH COOH AgOH PCl5 Hughes confirmed these facts by following experiment HO C C Cl C OH H KOH H H When optically active, (+) 2-iodooctane was treated with radioactive CH2 COOH CH2 COOH CH2 COOH sodium iodide in dry acetone solution, it not only exchanged ordinary iodide (–) Malic acid (+) Chlorosuccinic acid (+) Malic acid with radioactive iodide, but also lost its optical activity. It was observed that the rate of loss of optical activity was twice the rate of isotopic exchange. By these reactions, one enantiomer of malic acid is converted into another To account for the observed facts, it was concluded that the nucleophile by nucleophilic substitution at the chiral carbon atom. These reactions were * – I attacks from the backside and passes through the T.S. and inverts earlier known as Walden inversions. configuration. Hydrolysis of (–) 2-bromooctane gives (+) octan-2-ol.

CH6 13 CH – 6 13 CH6 13 CH6 13 CH * 6 13 I –* – * Aq.NaOH C I I C I I — C C Br HO C H –NaBr H CH H H H 3 CH 2 CH 3 reaction 3 CH3 SN CH3 (–) 2-Bromooctane (+) Octan-2-ol Alkyl Halides 7 8 College Organic Chemistry – S.Y.B.Sc. Since the rotation of the inverted molecule exactly cancels the rotation The three methyl groups of tert-butyl bromide sterically hinder the of unreacted molecule. Thus racemisation takes place. For every iodine atom approach of the nucleophile and thus prevent the backside attack. Therefore in substituted by radioactive iodine atom (I*) two molecules get racemised. the first step C–Br bond ionizes to give t-butyl carbocation and bromide ion.

Therefore, rate of loss of optical activity must be twice the rate of isotopic Due to gradual breaking of the bond a transition state (T.S)1 is formed. The exchange. Experimentally it is confirmed that the ratio of rate of racemization electron repelling inductive effect of the methyl groups facilitates the ionization, and the rate of iodine exchange is nearly equal to 2. by stabilising, carbocation. Further, the rate of reaction depended upon the concentration of alkyl Step (ii): Attack of nucleophile ( OH ): iodide as well as radioactive iodide ions, conforming its SN2 character. These facts prove that every SN2 reaction of chiral carbon atom results in the inversion CH CH CH3 of configuration. 3 3 + Backside Frontside + HO ---- C HO: + C + + :OH C ---- OH (ii) Mechanism of SN1 reaction (Substitution Nucleophilic attack attack CH Unimolecular) CH3 3 H3C CH3 CH3 CH3 (T.S.) Example: Mechanism of Alkaline hydrolysis of tert-alkyl halide. (T.S.)2 (Planer) 2 Consider the action of aqueous sodium hydroxide or potassium hydroxide on a tertiary alkyl halide such as t-butyl bromide. CH3 CH3 (CH ) CBr + KOH (CH ) COH + KBr 3 3 3 3 HO C t-Butyl aclohol C OH The ionic form of the reaction is: CH3 CH3 – CH CH3 (CH ) CBr + (CH ) COH + :Br 3 3 3 OH 3 3 Inversion Retention During this hydrolysis the stronger nucleophile, :OH– has displaced the weaker nucleophile, Br– and therefore, it is nucleophilic substitution (SN) The nucleophile ( OH) attacks the carbocation forming t-butyl alcohol. reaction. But due to gradual formation of the C–OH bond a transition state (T.S)2 is first Kineties of reaction: Experimentally is observed that the rate of the formed. The carbocation has planar configuration, hence it can be attacked by the nucleophile from either side. The frontside attack results in the product reaction depends only on the concentration of (CH3)3CBr and is independent of the concentration of the OH– ions, i.e., with retention of configuration. However, the backside attack results in the product with inversion of configuration. Since the attack from either side is Rate = k [(CH3)3CBr] equally probable, there will be retention in 50% of the molecules and inversion Therefore, this reaction is first order nucleophilic substitution reaction in the 50% of the molecules. 1 SN reaction. Energy profile diagram is obtained by plotting the potential energies Mechanism: This nuclephilic substitution takes place in two steps which of all the species against the reaction co-ordinates. The two-humps in the graph can be represented as follows. indicates two steps in the reaction. Step (i): Ionization of t-butyl bromide: Activation energy is the energy which must be supplied to reactants in order to form the transition state. It is equal to difference in potential energies

CH3 CH3 of reactants and the transition state. The step-(i) has a higher activation energy, CH3 Slow + hence it is slow. The step-(ii) has lower activation energy, hence it is fast. C Br C ----- Br C + Br CH CH 3 3 CH H3C 3 CH3 CH3 (T.S.)1 Carbocation Alkyl Halides 9 10 College Organic Chemistry – S.Y.B.Sc.

Step I Mechanism: It is a two step reaction: (T.S) 1 (i) In first step, the alkyl halide ionizes to form a carbocation and bromide

(CH3 ) 3 C ----- Br ion. The carbocation has trigonal planar structure and is achiral. Step II (T.S) (ii) In the second step, the nucleophile attacks from either side with equal 2 rate. The attack from the opposite side results in inversion of configuration (CH ) C ----- OH 3 3 and attack from the same side results in retention of configuration. Thus, the 1 y SN reaction results in almost complete racemisation. Thus, the faces of g r

e Ea carbocation are enantiotropic. 1 Ea2 n e

l Intermediate CH CH a 2 5 2 5 i CH2 5 t CH3 CH3 n – + e + t C Br C Br C Br o C CH + P + :Br 3 (CH ) Br + :OH H C CH 3 3 CH CH3 7 CH 3 3 7 H 3 3 Reactants CH3 7 (+) Isomer (T. S) (CH3 ) 3 C OH + :Br Product CH Reaction co-ordinates 2 5 1 HO C (Inversion) Fig. 1.2 Energy profile diagram of alkaline hydrolysis of t-butyl bromide by SN1 Backside mechanism. attack CH3 CH2 5 1 2 CH3 7 Ea = Energy of activation for step 1 1 C+ (–) Isomer Racemic H2 O: :OH + 2 –H mixture Ea2 = Energy of activation for step 2 CH2 5 CH3 CH H = Heat of reaction. 3 7 2 (Retention) In multi-step reactions the slowest step determines the overall rate of C OH reaction. This is called the rate controlling step. In the slow step only t-butyl Frontside attack CH bormide takes part and not the nucleophile. Hence it is a first order reaction. 3 CH3 7 (+) Isomer Stereochemistry However, the mixture is found to be slightly optically active. The bromide 1 SN reaction results in racemisation, e.g., when optically active 3-bromo- ion which is detached may take some more time to move away from the 3-methylhexane is heated with aqueous solution of acetone, the racemic mixture carbocation. Hence, the attack of nucleophile from the same side will be slightly of 3-methylhexan-3-ol is obtained. delayed. Hence, the product with inverted configuration will be slightly more. Hence, the mixture will be slightly optically active. Aqueous CH CH 2 5 CH2 5 2 5 1 2 CH3 COCH3 Factors Affecting SN and SN Reactions: C Br C OH + HO C CH 3 CH3 (i) Nature of substrate: As we go from primary to tertiary alkyl halides CH3 CH3 7 CH3 7 CH3 7 the stability of the corresponding carbocation increases (primary < secondary 1 (+) 3-Bromo-3-methylhexane (+) Isomer (–) Isomer < tertiary). Hence tertiary halides would prefer SN mechanism. Further, the crowding of the alkyl groups increases from primary to tertiary halides. Hence 3-methyl-3-hexanol (Racemic mixture) the attack of the nucleophile is hindered sterically by the alkyl groups. Hence, Alkyl Halides 11 12 College Organic Chemistry – S.Y.B.Sc.

2 SN type of mechanism can take place in primary halides where steric repulsion SN1 Reactions SN2 Reactions is minimum. (i) Rate of the reaction depends only Rate of the reaction depends on SN1 mechanism on concentration of alkyl halide concentration of alkyl halide and nucleophile Primary Secondary Tertiary (ii) Rate depends on the structure of Rate depends on the structure of o o o o halides in the order of 3 > 2 > 1 halides in the order of CH3X > 1 SN2 mechanism o o > CH3X > 2 > 3 . 2 (ii) Strength of nucleophile: In SN reaction the attack of nucleophile (iii) Reaction is favoured by more polar Reaction is favoured by less polar on the carbon atom takes place in the rate controlling step. Hence strong solvents. 2 1 nucleophiles are required to promote SN reaction. In SN reaction the (iv) Nature of the leaving groups does Nature of the leaving group nucleophile reacts with carbocation only in the fast step. Hence weak not affect position of reaction affects position of reaction nucleophiles like water can also result in SN1 reactions. equilibrium. equilibrium. (iii) Concentration of the base: With the increase in concentration of (v) The reaction takes place even with The reaction is favored by more weak nucleophile powerful nucleophile (strong the base the probability of attack of the base ( OH) on the carbon atom base). increases, hence SN2 reaction is favoured. In SN1 reaction the base ( OH) has to react with the cation. Hence low concentration of the base will be sufficient (iii) SNi Reaction 1 to cause SN reactions. When an alcohol is treated with , the hydroxyl group is (iv) Nature of Solvent: The polarity of the solvent has a marked affect replaced by chlorine atom. This is a nucleophilic substitution which follows a on the mechanism of the reaction. The SN1 reaction involves formation of a second order kinetics. When a chiral alcohol is used, there is no change in the carbocation which can be stabilised by solvents through solvation. Hence, configuration, i.e., there is retention of configuration. For example, more polar solvents favour SN1 reaction. Whereas, in SN2 reaction there is a CH CH dispersal of charge in the transition state. Hence, less polar solvent are sufficient 3 3 for SN2 reactions. C OH + SOCl2 C Cl + SO2 + HCl (v) Nature of leaving group: A group attached to the substrate which H H departs along with the electron pair from the molecule is called the leaving CH CH6 5 group. The nature of the leaving group also decides the mechanism. The basicity 6 5 is one of the factors, i.e., a weaker base is the better leaving group. For example, Mechanism: The reaction does not follow SN2 mechanism, as there is halides are good leaving groups as they are weak bases. The other factor is the no inversion of configuration. The alcohol first reacts with thionyl chloride size of the group, i.e., a larger group will be a better leaving group. Among forming an intermediate alkyl chlorosulphite (R-OSOCl) which can be isolated halogens, iodine being largest, acts as a better leaving group. under mild conditions. In this step, no inversion is possible as the bond between The –OH group is not a good leaving group but the aryl sulphonate chiral carbon atom and oxygen atom is not broken. Then the chlorosulphite 2 loses SO and forms an intimate ion pair. The intimate ion pair is short-lived (–OSO2Ar) is excellant leaving group. A good leaving group favours SN 2 reaction. intermediate in which the carbocation carbon and chloride are in close proximity. Before the carbocation changes its configuration, it combines with chloride ion to form alkyl chloride having similar configuration as the chiral alcohol. Alkyl Halides 13 14 College Organic Chemistry – S.Y.B.Sc.

O O State True or False CH3 CH3 S S (i) In SN2 of the reaction depends only on concentration of alkyl halide. C C OH + Cl Cl O Cl (ii) SN2 reactions proceed with stereochemical inversion called Walden inversion. H H –SO2 (iii) In SN1 reactions the rate of the reaction depend only on the concentration of CH6 5 CH6 5 alkyl halide. Alkyl chlorosulphite (iv) SN1 reactions are favoured by less polar solvent. CH (v) SN1 reactions result in racemization. 3 CH 3 i – From (vi) In SN reactions there is no inversion of configuration. C+ Cl Cl same side C  H H CH6 5 CH6 5 Intimate Retention of configuration ion-pair Due to the intimate ion-pair, the halide ion joins C-atom from the same side and does not allow any change in the configuration. Hence, there is no inversion of configuration even though the bond to the asymmetric carbon atom is broken. As the reaction is intramolecular, it is called substitution, nucleophilic internal, i.e., SNi reaction.

QUESTIONS

1. Explain the mechanism of alkaline hydrolysis of methyl bromide giving energy profile diagram. 2. Explain Walden inversion with example. 3. Explain with mechanism: Hydrolysis of (–) 2 bromooctane gives (+) octan-2-ol. 4. Explain the mechanism of alkaline hydrolysis of tert-butyl bromide giving energy profile diagram. 5. Explain with mechanism: SN1 reaction results in racemisation. 6. Distinguish between SN1 and SN2 reactions. 7. What are the factors which effect SN1 and SN2 reactions? 8. Explain with mechanism SNi reaction. 9. Explain the stereochemistry of the following reactions. (i) 2-Iodooctane + NaI (acetone) (ii) 3-Bromo-3-methyl hexane + Aqueous acetone (iii) 1-Phenyl ethanol + Thionyl chloride

PCl (iv) (–) Malic acid 5 (+) Chlorosuccinic acid AgOH (+) Malic acid.