Preview Organic Chemistry—A Modern Approach (VolumeII) by Nimai Tewari (2018)

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Organic chemistry a modern approach Volume-II About the Author Nimai Tewari is a retired Associate Professor in Department of Chemistry Katwa College (affiliated to University of Burdwan), West Bengal A Ph.D in Organic Chemistry from Calcutta University, he has taught the subject for a period of more than three decades He has published various research papers in national and international journals Apart from Organic Chemistry—A Modern Approach, Volume-II (including Volume-I of this title), Dr Tewari has authored four more books on Organic Chemistry for undergraduate and postgraduate students His research interest includes Organic Synthesis and Heterocyclic Chemistry Organic chemistry a modern approach Volume-II Nimai Tewari Associate Professor (Retired) Department of Chemistry Katwa College West Bengal McGraw Hill Education (India) Private Limited Chennai McGraw Hill Education Offices Chennai new York St Louis San Francisco auckland Bogotá Caracas Kuala Lumpur Lisbon London Madrid Mexico City Milan Montreal San Juan Santiago Singapore Sydney Tokyo Toronto McGraw Hill Education (India) Private Limited Published by McGraw Hill Education (India) Private Limited 444/1, Sri Ekambara Naicker Industrial Estate, Alapakkam, Porur, Chennai 600 116 Organic Chemistry—A Modern Approach (Volume-II) Copyright © 2018, by McGraw Hill Education (India) Private Limited No part of this publication may be reproduced or distributed in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise or stored in a database or retrieval system without the prior written permission of the publishers The program listings (if any) may be entered, stored and executed in a computer system, but they may not be reproduced for publication This edition can be exported from India only by the publishers, McGraw Hill Education (India) Private Limited D102739 22 21 20 19 18 Printed and bound in India ISBN (13): 978-93-87886-19-3 ISBN (10): 93-87886-19-0 Director—Science & Engineering Portfolio: Vibha Mahajan Senior Portfolio Manager: Suman Sen Associate Portfolio Manager: Laxmi Singh Senior Manager—Content Development: Shalini Jha Content Developer: Ranjana Chaube Production Head: Satinder S Baveja Sr Manager—Production: Piyaray Pandita General Manager—Production: Rajender P Ghansela Manager—Production: Reji Kumar Information contained in this work has been obtained by McGraw Hill Education (India), from sources believed to be reliable However, neither McGraw Hill Education (India) nor its authors guarantee the accuracy or completeness of any information published herein, and neither McGraw Hill Education (India) nor its authors shall be responsible for any errors, omissions, or damages arising out of use of this information This work is published with the understanding that McGraw Hill Education (India) and its authors are supplying information but are not attempting to render engineering or other professional services If such services are required, the assistance of an appropriate professional should be sought Typeset at Text-o-Graphics, B-1/56, Aravali Apartment, Sector-34, Noida 201 301, and printed at Cover Printer: Visit us at: www.mheducation.co.in Write to us at: info.india@mheducation.com CIN: U22200TN1970PTC111531 Toll Free Number: 1800 103 5875 Dedicated to Sri Ramakrishna Paramhansa Contents Preface Addition to Carbon–Carbon Multiple Bond Introduction 1.1 1.1 Electrophilic Addition 1.2 1.1.1 Addition of Hydrogen Halides 1.6 Solved Problems 1.14 Study Problems 1.22 1.1.2 Addition of Water and Alcohol 1.26 Solved Problems 1.32 Study Problems 1.37 1.1.3 Oxymercuration-Demercuration 1.39 Solved Problems 1.42 Study Problems 1.44 1.1.4 Addition of Halogens 1.45 Solved Problems 1.56 Study Problems 1.62 1.1.5 Hydroboration-Oxidation 1.65 Solved Problems 1.75 Study Problems 1.81 1.1.6 Ozonolysis of Alkenes and Alkynes 1.82 Solved Problems 1.93 Study Problems 1.100 1.1.7 Addition of Carbenes and Simons-Smith Reaction 1.102 Solved Problems 1.110 Study Problems 1.115 1.1.8 Hydroxylation of Alkenes 1.117 Solved Problems 1.127 Study Problems 1.131 1.1.9 Hydrogenation 1.134 Solved Problems 1.142 Study Problems 1.147 xiii 1.1–1.212 Contents viii 1.1.10 Diels–Alder Reaction 1.149 Solved Problems 1.163 Study Problems 1.175 1.2 Nucleophilic Addition 1.178 1.2.1 Cyanoethylation 1.178 1.2.2 Direct and Conjugate Addition to a, b-Unsaturated Aldehydes and Ketones 1.180 1.2.3 Michael Addition or Michael Reaction 1.182 Solved Problems 1.186 Study Problems 1.195 1.3 Addition of Radicals and Radical Substitution of Benzylic and Allylic Hydrogens 1.199 1.3.1 Radical Addition of Halogens and Hydrogen Halides and Radical Polymerization 1.200 Solved Problems 1.205 Study Problems 1.206 1.3.2 Allylic Chlorination and Allylic Bromination 1.207 Solved Problems 1.209 Study Problems 1.211 References 1.212 Reactions of the Carbonyl Group and Reactions at the a-Carbon to the Carbonyl Group 2.1–2.346 2.1 Introduction 2.2 2.2 Nucleophilic Addition to Carbon-Oxygen Double Bond 2.5 2.2.1 Structure of the Carbonyl Group 2.5 2.2.2 Effect of Structure on Reactivity 2.5 2.2.3 Stereochemistry of Nucleophilic Addition 2.8 Solved Problems 2.10 2.3 Addition of Oxygen Nucleophiles: Water and Alcohols (ROH) 2.11 2.3.1 Addition of Water (Hydration) and Formation of gem-diols 2.11 2.3.2 Mechanism for Hydrate Formation 2.11 2.3.3 Kinetics of Hydrate Formation 2.11 2.3.4 Thermodynamics of Hydrate Formation 2.13 2.3.5 Formation of Stable and Isolable Hydrates 2.14 2.3.6 Addition of Alcohols and Formation of Hemiacetals and Acetals 2.16 2.3.7 Mechanism for Acid-catalyzed Hemiacetal and Acetal Formation 2.18 2.3.8 Mechanism for Base-catalyzed Hemiacetal Formation (Base-catalyzed Acetal Formation does not take place) 2.20 2.3.9 Hydrolysis of Acetals 2.20 2.3.10 Acetals as Protecting Groups 2.22 2.3.11 Tetrahydropyranyl Group as a Protecting Group 2.23 Solved Problems 2.24 Study Problems 2.33 Contents ix 2.4 Addition of Sulphur Nucleophiles: Thiols (RSH) and Sodium Bisulphite (NaHSO3) 2.38 2.4.1 Addition of Thiols 2.38 2.4.2 Mechanism for Thioacetal Formation 2.38 2.4.3 Thermodynamics for Thioacetal Formation 2.39 2.4.4 Importance of Thioacetals in Organic Synthesis 2.39 2.4.5 Addition of Sodium Bisulphite (NaHSO3) 2.40 2.4.6 Mechanism for Bisulphite Additions 2.40 2.4.7 Applications of Bisulphite Addition Reaction 2.41 Solved Problems 2.42 Study Problems 2.45 2.5 Addition of Hydride Ion (:H①) and addition of electrons 2.46 2.5.1 Reduction of carbonyl compounds by lithium aluminium hydride (LiAlH4) 2.47 2.5.2 Mechanism for the reduction of carbonyl compounds by lithium aluminium hydride (LiAlH4) 2.47 2.5.3 Reduction of aldehydes and ketones by sodium borohydride (NaBH4) to form primary and secondary alcohols, respectively 2.50 2.5.4 Mechanism for the reduction of an aldehyde or a ketone by sodium borohydride (NaBH4) 2.51 2.5.5 Reduction of carboxylic acids, amides and nitriles by borane (BH3) 2.51 2.5.6 Reduction of Acid Chlorides to the Corresponding Aldehydes by Lithium tri-tert-butoxyaluminium Hydride [LiAlH(O-t-Bu)3] and Reduction of Esters and Nitriles to the Corresponding Aldehydes by Diisobutylaluminum Hydride (i–Bu2AlH or DIBAL–H): 2.53 2.5.7 Meerwein–Ponndorf–Verley (MPV) reduction 2.55 2.5.8 Cannizzaro Reaction 2.57 2.5.9 Tishchenko Reaction 2.64 2.5.10 Bouveault-Blanc Reduction 2.65 2.5.11 Pinacolization of Ketones 2.67 2.5.12 Clemmensen Reduction 2.68 Solved Problems 2.69 Study Problems 2.81 2.6 Addition of Nitrogen Nucleophiles 2.84 2.6.1 Addition of Primary Amines and Formation of Imines 2.84 2.6.2 Addition of Compounds like Hydroxylamine, Hydrazine and Substituted Hydrazines (Similar to Primary Amines and Formation of Imine Derivatives) 2.86 2.6.3 Reductive Amination 2.88 2.6.4 Wolff-Kishner Reduction 2.89 2.6.5 Important uses of the Imine-Forming Reaction 2.91 2.6.6 Addition of Secondary Amines and Formation of Enamines 2.91 Solved Problems 2.96 Study Problems 2.104 Contents x 2.7 Addition of Carbon Nucleophiles 2.106 2.7.1 Addition of Hydrogen Cyanide (HCN) 2.106 2.7.2 Addition of Grignard and Other Organometallic Compounds 2.109 2.7.3 Addition of Acetylides 2.116 2.7.4 Addition of Diazomethane (CH2N2) 2.116 2.7.5 Addition of Ylides 2.118 Solved Problems 2.127 Study Problems 2.142 2.8 Addition of Enolate Ions 2.145 2.8.1 Aldol Reactions 2.145 2.8.2 Stobbe Condensation 2.157 2.8.3 Darzenes Condensation 2.160 2.8.4 Benzoin Condensation 2.164 2.8.5 Reformatsky Reaction 2.169 2.8.6 Perkin Reaction 2.172 2.8.7 Knoevenagel Condensation 2.175 2.8.8 Mannich Reaction 2.180 Solved Problems 2.182 Study Problems 2.203 2.9 Reactions at the a-carbon of Carbonyl Compounds of Aldehydes and Ketones 2.208 2.9.1 Halogenation at the a-carbon of Aldehydes and Ketones 2.208 2.9.2 Alkylation at the a-carbon of Aldehydes and Ketones 2.214 2.9.3 The Claisen Condensation (Addition of Acid Derivatives to the a-carbon of Carbonyl Compounds) 2.227 Solved Problems 2.236 Study Problems 2.273 2.9.4 Green Chemistry 2.279 Solved Problems 2.283 Study Problems 2.285 2.10 Acyl Substitution 2.286 2.10.1 Mechanism of Nucleophilic Addition–Elimination at the Acyl Carbon or Nucleophilic Acyl Substitution 2.286 2.10.2 Reactions of Carboxylic Acids 2.290 2.10.3 Reactions of Acid Chlorides 2.311 2.10.4 Reactions of Esters 2.313 2.10.5 Reactions of Amides 2.317 2.10.6 Reactions of Carboxylic Acid Anhydrides 2.319 2.10.7 Reactions of Nitriles 2.320 Solved Problems 2.321 Study Problems 2.341 References 1.346 1.95 Addition to Carbon–Carbon Multiple Bond Draw the products obtained when each of the following alkynes is treated with O3 followed by H2O2: (a) (c) CH3C ∫∫ C CH2CH2C ∫∫ CH (b) Solution (a) (b) (c) O CH3C ∫∫ CCH2CH2C ∫∫ CH ỉỉỉỉỈ CH3COOH + H2OCCH2CH2CO2 H + CO2 H O Write structures of the alkenes that would yield the following carbonyl compounds when treated with O3 followed by Me2S or Zn/H2O (give stereochemistry when appropriate): (a) CH3CH2CHO + (CH3)2CHCHO (b) CH3CO(CH2)4CHO (c) only 2-butanone (e) (R)-2-Ethylcylopentanone (i) 2CH3CH2CHO + CO2 (m) Solution (d) (f) CH3CH2CHO + CH3COCHO + HCHO (g) (k) (a) (h) (S)-2-Ethylcyclopentanone (j) 2CH3COCH2CH3 + 2CO2 (l) 1.96 (b) (c) (d) (e) Organic Chemistry—A Modern Approach Addition to Carbon–Carbon Multiple Bond (f) (g) (h) (i) 1.97 1.98 Organic Chemistry—A Modern Approach (j) (k) (l) (m) X, Y and Z are stereoisomeric forms of the reaction product What are X, Y and Z? Designate them as chiral or achiral What product would be formed if the methyl groups were cis or trans to each other in the starting alkene Solution The trans-diastereoisomer of the starting alkene exists as two enantiomeric forms On ozonolysis, one enantiomer leads to the formation of the chiral dialdehyde X and the other enantiomer leads to the formation of the enantiomeric dialdehyde Y On the other hand, when the cis-diastereoisomer (which exists as inseparable dl-pair) of the starting alkene is subjected to ozonolysis, it produces the achiral meso-compound Z Addition to Carbon–Carbon Multiple Bond 1.99 Explain why ozonolysis of o-xylene produces a mixture of dimethyl glyoxal, methyl glyoxal and glyoxal in 1:2:3 ratio Solution o-Xylene is a resonance hybrid of structures I and I Therefore, ozonolysis of this compound may take place through both the structures From structure I, glyoxal and methyl glyoxal are obtained in 1:2 ratio 1.100 Organic Chemistry—A Modern Approach On the other hand, from structure II, glyoxal and dimethyl glyoxal are obtained it 2:1 ratio Therefore, ozonolysis of o-xylene produces a mixture of dimethyl glyoxal, methyl glyoxal and glyoxal in a 1:2:3 ratio Give an example of an alkene that will form the same products on ozonolysis regardless of whether the ozonide is worked-up under oxidizing conditions (H2O2) or reducing conditions (Zn/H2O or Me2S) [Hint: The alkene which gives two ketone molecules on ozonolysis.] Draw the products formed when each of the following alknes is treated with O3 followed by Me2S: (a) (b) (c) (d) (e) (f) What alkene forms the following set of products after reaction with O3 followed by Me2S? (a) OHC (CH2)4COCH3 (c) CH2 == C == C == C(CH3)2 (b) (d) (e) Me2CO + CO2 (f) CH3COCH2CH2 CHCH2 CHO + HCHO | COCH3 (g) CH3CH2CHO only (h) CH3COCH2CH3 only What aspect of alkene structure cannot be determined by ozonolysis? Draw the products obtained when each of the following alkynes is treated with O3 followed by H2O2: 1.101 Addition to Carbon–Carbon Multiple Bond 10 (a) Ph — C ∫∫ C — Ph (b) CH3CH2C ∫∫ C CH3 (c) CH3CH2CH2CH2C ∫∫ CH (d) CH3CH2C ∫∫ CCH2CH2C ∫∫ CH What alkyne (or diyne) yields each set of products when treated with O3 followed by H2O2? (a) (CH3)2CHCH2COOH + CO2 (c) (CH3)2CHCH2COOH only (b) HO2C(CH2)14CO2H (d) CH3CH2CH2COOH + HO2C CH2CH2CO2H + CH3CO2H Oximene and myrcene are two isomeric hydrocarbons (C10H16) On catalytic hydrogenation, both yield 2,6-dimethyloctane On ozonolysis, oximene yields CH3COCH3, HCHO, CH2(CHO)2 and CH3COCHO and myrcene yields (CH3)2CO, HCHO (two equiv.) and OHCCH2CH2COCHO Identify the structures of oximene and myrcene Compound A (C10H16) consumes two moles of H2 on catalytic hydrogenation When A is treated with O3 followed by reductive work-up, two diketones, B(C6H10O2) and C(C4H6O2) are obtained Suggest a reasonable structure (or structures) for A Compound A (C8H12) reacts with two moles of H2 A produces butanedial (OHCCH2CH2CHO) as the only product when treated with O3 followed by reductive work-up with Zn/H2O Identify A Suggest a mechanism for the following reaction: 11 Write down the structure and configuration of the alkene that give a mixture of (R)- and (S)-2-methycylclobutanone on treatment with O3 followed by Me2S 12 Determine the structure of the compound A(C10H14) that on catalytic hydrogenation consumes three moles of H2 to yield 1-isopropyl-4-methylcyclohexane A on reductive ozonolysis gives the following compounds: HCHO; OHC CH2COCOCH3; CH3COCH2CHO 13 14 15 Write down all possible structures for the compound X(C10H16) that undergoes oxidative and reductive ozonolysis to yield two moles of the same compound Y (C5H8O) X consumes three moles of H2 in the presence of catalyst None of these two compounds is resolvable A tertiary alcohol is dehydrated to yield an alkene When the alkene is treated with O3 followed by Zn/H2O, equal amounts of 3-pentanone and ethanal are obtained Find out the structure of the alcohol Predict the structure of an aromatic hydrocarbon which on treatment with O3 followed by Zn/H2O produces CH3COCHO and CHC — CHO in 2:1 molar ratio 1.102 16 17 Organic Chemistry—A Modern Approach Which of the following two olefins is more prone towards ozonolysis reaction and why? Me2C == CMe2 and Me2 C == C(CO2Et)2 I II [Hint: The double bond in I is more electron rich and so, it is more prone towards ozonolysis.] Identify the diastereoisomic compounds A, B, C and D in the following reaction: 2O A or B or C or D ỉỉỉỉ Ỉ CH 3CH 2CHO + OHC — CHO + C2H5CHO Me S 19 [Hint: cis-cis, trans-trans, cis-trans and trans-cis isomers of 2,4-heptadiene.] Write down the two possible enol forms of hexane-2,4-dione and give the products expected to be formed on their ozonolysis Suggest a mechanism for the following reaction: 20 Treatment of I with O3 in solvent acetone leads to II as the major product Explain 18 1.1.7 1.1.7.1 Addition of carbenes and Simons-Smith reaction Carbenes and Their Classification on the Basis of the Spin States of Electrons Carbenes are electrically neutral reaction intermediates containing a bivalent carbon atom in which the C atom is covalently bonded to two other atoms or groups and has two other valence electrons distributed between the two nonbonding orbitals, i.e., carbenes are neutral species containing a carbon with only six valence electrons The general formula of carbenes is :CR2 The simplest member :CH2, often called methylene or simply carbene, is the parent Carbenes are named by mentioning the substitutes attached to the divalent carbon, e.g., :CBr2, dibromocarbene; :CHPh, phenylcarbene, etc However, when the divalent carbon of a carbene is a part of a ring or an unsaturation, suffix -ylidine is used For example: Addition to Carbon–Carbon Multiple Bond 1.103 Depending upon the spin states of the nonbonding electrons, carbenes are divided into two classes If the two nonbonding electrons remain spin paired, it is called a singlet carbene, while the carbene having unpaired spins of electrons is referred to as a triplet carbene 1.1.7.2 Structure and Stability of Carbenes The C atom in a singlet carbene is sp2-hybridized (trigonal hybridization) Two of these three sp2 hybrid orbitals are utlized in forming covalent bonds, while the third hybrid orbital contains the unshared pair of electrons There remains a vacant p orbital A singlet carbene, therefore, resembles a carbocation and it appears to have a bent shape (bond angle 100–110∞) Although a few triplet carbenes are linear (sp-hybridized), most of them are bent species (bond angle 130–150∞) where the carbon is sp2-hybridized, and the two nonbonding electrons occupy an sp2 orbital and an unhybridized p orbital with parallel spin Carbenes are generally more stable (about 40 kJ mol–1) as triplets because the energy to be gained by bringing the electron in the p orbital down into the sp2 orbital is insufficient to overcome the repulsion that exists between two electrons in a single orbital The triplet state of carbene is, therefore, expected to be the ground state It is to be noted that the dihalocarbenes are singlet in the ground state, i.e., they are more stable than the corresponding triplets because they are considerably stabilized by resonance involving unshared p electrons of the halogen atom with the vacant p orbital on carbon Because of similar size of the overlapping orbital of fluorine and carbon (very effective 2p–2p overlap), the resonance interaction is much more effective in :CF2 and so, singlet variety of :CF2 is much more stable than its triplet variety 1.104 Organic Chemistry—A Modern Approach 1.1.7.3 Equilibrium Between the Two Spin States and Reactivity All carbenes have the potential to exist in either the singlet state or the triplet sate (the two species remain in equilibrium), so what we mean when we say that :CH2 is a triplet carbene, the triplet state for this carbene is more stable (lower in energy) than the singlet state Even though there is more triplet carbene present at equilibrium, its reactions cannot compete with those of the small amount of the much more reactive singlet carbene and this is because the activation barriers surrounding the less stable singlet carbene is substantially lower than those surrounding the more stable triplet carbene It is for this reason, most of the chemistry of carbene comes from the singlet, i.e., reactions of the singlet are the ones that are normally observed 1.1.7.4 Generation of Carbenes Carbenes can be generated from diazoalkanes, ketenes, ylides, epoxides and cyclopropane derivatives by thermal or photochemical decomposition and by a-elimination involving formation of carbanions (a) From diazoalkanes: The photolysis or thermolysis of diazoalkanes in aprotic solvents provides the most common root to carbenes For example: Methylene (:CH2) is formed when diazomethane is subjected to photolysis or thermolysis ≈ @ @ ≈ D or hn  H — N ∫∫ N] æææææææ  : ´ C [CH == N == N Ỉ :CH + N2 aprotic solvent Diazomethane (b) From ketenes: Ketenes on pyrolysis or photolysis loose carbon monoxide to form carbenes For example: 1.105 Addition to Carbon–Carbon Multiple Bond D or hn ( l == · 280nm) CH2 ==C ==O or Ph 2C == C == O ỉỉỉỉỉỉỉỉỉ Ỉ :CH2 or Ph 2C : + CO Diphenylketene Ketene Methylene Diphenylcarbene (c) From ylides: Carbenes can be generated by photolysis or thermolysis of sulphur, phosphrus and nitrogen ylides For example: @ ≈ hn  : CHCOPh Me2 S — CHCOPh ỉỉỉ Ỉ + Me2S Benzoylcarbene A sulphur ylide ≈ @ D  Ph ææ : CHPh Ph P — CH Ỉ + Ph P Phenylcarbene A phosphorus ylide ≈ @ D  : CH Me3 N — CH ỉỉ Ỉ + Me3 N 2 Methylene A nitrogen ylide (d) From epoxides: Phenyl substituted carbenes are formed from phenyl substituted oxiranes or epoxides by photolysis For example: (e) From cyclopropane derivatives: Photolysis or thermolysis of cyclopropane derivatives leads to the formation of carbenes For example: (f) From gem-dichloro alkanes: When gem-dichloroalkanes are treated with metallic lithium, carbenes are generated For example: (g) By a-elimination reactions: Carbenes can be generated by a-elimination reactions in which both the atoms/groups are lost from the same carbon For example: 1.106 1.1.7.5 Organic Chemistry—A Modern Approach Stereospecific addition of a singlet carbene and nonstereospcific addition of triplet carbene to C==C bond to give cyclopropanes The addition of a singlet carbene to an alkene (an electrophilic addition) is a concerted process (the two s bonds are formed simultaneously) as the unshared electrons of the carbene are in favourable spin for ready bond formation In this process, the original stereochemical relationship of the groups on the alkene is preserved, i.e., the addition is stereospecific and syn It thus follows that singlet carbene reacts with cis-2-butene to yield a cis- cyclopropane and reacts with trans-2-butane to yield a trans- cyclopropane Addition to Carbon–Carbon Multiple Bond 1.107 A triplet carbene, which is diradical in nature, adds to the carbon–carbon double bond of cis-2-butene, for example, by a free radical two-step pathway involving addition followed by recombination As the two unpaired electrons in a triplet carbene have parallel spins, there is spin restriction on the simultaneous formation of two s bonds In the first step of this reaction, one of the unpaired electrons forms a s bond with that p-electron which has the opposite spin and as a result, a diradical is formed The diradical with two unpaired electrons having parallel spin (a triplet intermediate) undergoes spin-flipping by some appropriate collisions and then form the other s bond to give a cis-cyclopropane Since spin-flipping is relatively slow on the time scale of molecular rotation, a free rotation about the C — C bond takes place during this time Spin-flipping followed by ring closure then produces a trans-cyclopropane The reaction is, therefore, nonstereospecific (stereoselective) Trans-2-butene, by a similar process, produces a mixture of a cis- and a trans-cyclopropane 1.108 1.1.7.6 Organic Chemistry—A Modern Approach Nucleophilic Carbenes Because of electron deficiency (incomplete octet of carbon), carbenes are normally electrophilic However, there are some carbenes in which the singlet structures are stabilized by incorporating the vacant p orbital into some delocalized electronic system and as a consequence of resonance interaction, their electrophilic character is suppressed and nucleophilic character is developed Such carbenes are called nucleophilic carbenes For example: (i) (ii) 1.1.7.7 Carbenoids and the Simmons–Smith Reaction Although dihalocarbenes react with alkenes to give cyclopropanes in good yield, this is not usually the case of methylene, :CH2, the simplest carbene The reaction of :CH2 with alkene often produces a complex mixture of products and therefore, the reaction cannot be reliably used for cyclopropane synthesis A useful cyclopropane synthesis was developed by H.E Simmons and R D Smith in 1959 When alkenes are treated with methylene iodide (CH2I2) in the presence of zinc-copper couple (zinc dust that has been activated with an impurity of copper), cyclopropanes are obtained, this reaction is called the Simmons–Smith reaction For example: The active reagent in this reaction is the a-haloorganometallic compound (a compound with halogen and a metal on the same carbon) ICH2ZnI obtained by the following reaction similar to the formation of a Grignard reagent CH 2I2 + Zn(Cu) ỉỉ Ỉ I — CH — ZnI Simmons-Smith reagent (a carbenoid) This kind of reagent is termed a carbenoid because it it not a free carbene but has carbenelike reactivity 1.109 Addition to Carbon–Carbon Multiple Bond Mechanism: A concerted stereospcific transfer of methylene (:CH2) from the carbenoid to the double bond of the alkene takes place to create a cyclopropane ring This addition, like the addition of dichloromethylene, is a syn-addition The reaction occurs as follows: Cyclopropanation by the Simmon–Smith reaction is preferred over that involving diazomethane because diazomethane is toxic and at the same time it is explosive in nature Furthermore, free :CH2 inserts in bond to yield No such problem arises in reactions involving carbenenoids When an allylic alcohol, for example, 2-cyclohexenol, is subjected to the Simmons–Smith reaction for cyclopropanation, the methylene group adds stereoselectively to the same face of the double bond as the — OH group Furthermore, the reaction occurs at a much faster (100 times) rate than their unfunctionlized alkene equivalents The stereoselectivity and the rate enhancement can be explained by the coordination between Zn atom and the hydroxyl group The mechanism of the reaction is as follows: ... international journals Apart from Organic Chemistry—A Modern Approach, Volume-II (including Volume-I of this title), Dr Tewari has authored four more books on Organic Chemistry for undergraduate... postgraduate students His research interest includes Organic Synthesis and Heterocyclic Chemistry Organic chemistry a modern approach Volume-II Nimai Tewari Associate Professor (Retired) Department... number of hydrogen atoms’ 1.8 Organic Chemistry—A Modern Approach d+ d- Y—Z RCH == CH2 + ỉỉỉỉ Ỉ RCHZ — CH2 Y (YZ == H2O, H2SO2 , ICl, etc.) Modern statement: The modern statement of the Markownikoff