A chemical reaction is a process which changes the structure of at least one of the starting materials and hence gives rise to new species. Usually this involves collision between two chemical units of the starting materials in which one or more of their bonds break and new bond or bonds form and thus new species develop. In an organic reaction, the main organic entity which is converted into a new one by the processes of breaking and making of bonds is known as a reactant or and the new one formed is named as a j the chemical entity which causes the change is called a The bond breaking and bond making processes of an organic entity may take place in three ways : ‘These may occur as separate steps. ‘The two processes may overlap—before breaking of a bond completely, a new bond may begin to form. ‘These may occur at a time—this is known as a concerted step. After the process of bond breaking, intermediate entities are often formed momentarily during the course of chemical reactions; these are very important to understand chemical reactions and are said to be ‘The nature of reaction intermediate and that of the product in a chemical reaction depend on: I. Constitutional features of the entities involved, i.e., mode of arrangement of their constituent atoms and electron availability within the entities. II. Stereochemical features including stereoelectronic features, i.e., orientation of constituent atoms and that of the orbitals of the entities in space. IIL. Nature of the reagents that are taking part in the reaction. IV. Nature of the solvent that is employed for the reaction. Of course thorough ere a chemical reaction requires the knowledge of energy changes involved in the system as a whole. This includes: ‘Thermodynamics of the reaction—to know the ratio of reactant and product in a particular step when the reaction goes to the equilibrium. Kinetics of the reaction—to know the rate at which the reaction occurs. Most of the organic reactions consist of more than one step and a number of products may result in a single reaction, Why one of these possible products actually perdominates and why other products form in practice are determined by the detailed description of the overall course of the reaction including: (») Constitutional and stereochemical features of the entities. ‘») Bond-breaking and bond-making processes. (-) Thermodynamics and kinetics of the reaction. ‘This overall description of the reaction course is termed as reaction mechanism. ‘The mechanism of a reaction must tally with all the facts available about the reaction. If new facts about the very reaction are discovered, the mechanism proposed may change. In fact, 501Advanced General Organic Chemistry never known to be complete; and for this reason, we call the mechanism for a reaction is p Beh ois for most of the reactions as plausible mechanisms. However jc reacti tly molecules and and the products of the organic reactions are mostly Oa uc Riesicy bes discussed in different chapters. In this chapter we shall oa our attention to the processes involved in between the reactant state and the product state. ‘This requires the discussion of the following subjects: A. Elementary classification of reactions. B. Breaking and making of bonds. C. Types of reaction intermediates. D. Types of reagents. B. Thermodynamics of the reactions (Chapter five). F. Kinetics of the reactions (Chapter six). G. Stereochemical features (Chapter nine). H. Relationship between these things and structures. 1. Methods of determining mechanisms. Organic reactions may be broadly classified under four heads: 1. Substitution or displacement reaction—In which an atom or a group of atoms are replaced by another atom or group; for instance, hydrolysis of methyl chloride to methyl alcohol by aqueous caustic soda solution. Here the Cl atom is replaced by the OH group. . NaOH Hc. 2" -. cHon In which two molecules unite to produce a single molecule; this is com mon to compounds containing multiple bonds. Thus bromine in carbon tetrachloride undergoes addition reaction with ethylene to give rise to ethylene bromide. 2. Addition reaction. Br2/CCl, Gayoso, CH Br.CH2Br 3. Elimination reaction—In which two atoms or groups are removed from a single molecule; the process is the reverse of addition reaction. If elimination of two ator cn fom no anes he haan nee eater rocess of elimination may occur from two adjacent atoms of the molecule and this is known as B-elimination; in this ease formation of multiple bond is the result, Elimination may als» take place from atoms separated by one, two or more atoms; these are then called 7, 6, etc. Petition reactions. In such cases usually rings are formed. When ethyl alcohol is heated with cone. H,SO at 170°C we get ethylene and water which gets absorbed by conc. Hy80s—thi i as car #-elimination reaction. P 170°C Cone, H2SO4 + CHsCH,0H CHa = CH + [S04 +1130) 4, Reorangenicnt voction—In which one or more isomeric compo phenetole is heated at 150°C in the presence of anhydrous AlCly, o- are produced. unds are formed, e.g., when ethylphenol and p-ethylphenolFundamentals of Organic Reaction Mechanis!) ——_—_——__ 5(3 OEt OH OH Et 150°C anh. AlCly a Et : Phenetole o-Ehylphenol p-Ethylphenol Besides these four general types, one may find the names of several other reactions; e.g., {a) Oxidation reduction or redox reaction—In which change in oxidation number of an atom or atoms occur; thus conversion of methyl alcohol into formaldehyde involves increase in oxidation number of the C atom from —2 to 0. Aldehydic C has +I oxidation state in acebaldehyde; in ethyl alcohol, that C has —I oxidation state. oxidation reduction =I 0 +1 -1 CH30H HCHO; CH3CHO CH,CH,0H (b) Condensation reaction—In which two or more molecules unite with or without loss of small units; thus condensation of two molecules of acetaldehyde gives rise to one molecule of aldol. OH- CHjCHO + CH;CHO ——— CH,CHOH-CH,CHO Polymerisation reaction—In which a large number of species unite to form a macro species. A large number of ethene molecules unite to form polyethene. These may be considered as reactions involving one or more of the substitution, addition or elimination types of reactions. Reaction intermediates undergo certain reactions which cannot be explained by the general types of reactions; e.g., (i) Fragmentation or decomposition reaction—in which a species cleaves into two other species. (ii) Coupling reaction—in which two species unite to form a single species. (iii) Atom abstraction reaction—in which one atom, H atom in most of the cases, is taken out from a species. (iv) Insertion reaction—in which one species is inserted between two o-bonded atoms in another species. (© ‘As stated earlier, a covalent bond between two atoms in a molecule, A—B, may be looked upon as a shared pair of electrons and thus may be represented as A: B. ‘When the bond between A and B is broken, the molecule breaks into two species. The way in which a bond is broken determines the nature of the species formed. Both theory and practice tell us that a covalent bond can be broken in two ways: homolytic fission heterolytic fission 1. Homolytically ; A—B, ie., A: B A+B. 2. Heterolytically ; A—B, ie, A: B A®+ Bi or Al + B®i ne He je cleavage or fission of a bond, i.e., homolysis separates td i pene h one eee of the shared pair and thus A+ and B: are formed from “ Mite aan pe hie benad ‘now assumes the electron configuration of its initial aa Mii Pies cated a sharged species with unpaired electron and are known as free rage * ; 1 Aa dic know Roig rare). Free radicals containing ‘odd electrons on C atoms are collectively called carbon radicals. ,,, Homolysis of a bond is carried out either in the gas-phase or in the pare Riss “i : “4 of heat, light, radioactive elements, organic peroxides, ce Soe i nen ee a are called initiators. Reactions involvin, bon radicals are called : : ., Tt is obvious that in the homolytic fission of bonds, the reagent primarily eich Si P d which are most easily breakable, i.e., possessing low bond dissociation eet Es or im a of a bond is the most characteristic reaction of the paraffins. The C— : pra Ph i first attacked and then by the process of chain reactions C—C bonds also : reak. Py required to break up C—H bonds in some of the hydrocarbons are given below in Ta! ‘Table 11.1 Homolytic bond dissociations energy of C—H bonds Compound Energy in Compound = Energy in kJ mol? kJ mol~! HCH 431.2 CHy=CH.CHa—H 322.4 ol ater ad i (Gites 380.9 ClhC—H 372.7 mg TAS er 808.8" PMN ato ‘When the fission of a bond gives rise to two ions, a cation and an anion, the proces: as heterolytic fission or cleavage, or heterolysis. Which one of the bonded atoms will be c: or anion that depends on whether A or B retains the bonded electron pair. me If in a cation, formed by the heterolysis of a bond, a C atom bears the positive known as a carbenium ion; a carbenium ion is an electron-deficient centre. On the if there is a negative charge on a C atom in an anion, electron rich centre. charge other hand, it is said to be a carbanion; it is an Reactions involving carbenium ions or carbanions are termed as polar or coctions, Carbenium ions are also called carbocations. Carboniuin ions are Jerivatives, Heterolysis of bonds are generally carried out in ions, Bond breaking process requires input of energy. Nature of the reagent, the solvent and the atoms that are present in the substi te collectivel determine the bond to be broken in the substrate, Brente collec Polar solvents by means of acids, bases or Sie mE Aura cesta The bond-formation process is the reverse of bond-breaking process. Attack by the radica! or ions to other species gives rise to new bonds. Coupling teaction, abstraction of png ares groups, etc. form new bonds, Bond formation processes liberate energy. iFundamentals of Organic Reaction Mehanisi, OD (5) The chemical reactions in which more than one bond is broken or formed are usually classified under two heads~(i) Concerted step reactions and (ii) Stepwise reactions (i) Concerted step reactions : In which all the bond forming and bond breaking processes occur in concert, i iultaneously so that at one step the conversion of reactants to products takes place without the formation of any intermediate, a stable molecule or a highly unstable transient species (called a reaction int mediate). The concerted step reactions are also called multicentered reactions since several bonds take part at the same time at more than one centre. When ethyl acetate is pyrolysed, acetic acid and ethylene are formed; this is in example of concerted step reaction as shown below. Here one C—O 7 bond, one C—H o bond and one O—C ¢ bond break and one C-—O 7 bond, one C—C z-bond and one O—H @ bond form in concert 0, si CH 2. CH, CHys tee an a i 3 ae te : + Qi On CH) ON, CH, a multi-centred T.8 In a concerted step reaction all bond breaking and bond making processes are inter-dependent 40 that both processes are going on at the same time and the energy required for the bond breaking is somewhat compensated by the energy evolved through the bond making. However, the two processes may be synchronous, i.e., can occur exactly at the same rate or it may not be. There are concerted step reactions in which one process starts before the other but does not end before the other process begins. The two processes will overlap at one time and the bond breaking or bond making process will couple with and controlled by the other process. Though there will be a time lag between their start, the reactions will still be considered as the concerted step reactions. A concerted step reaction involves only one energy barrier and a single transition state. The energy ion is drawn below : [7 Acuna Reaction progress —> a » Fig, 11.1. a The energy profile for an endothermic concerted step reaction The energy profile for an exothermic concerted step reaction profile for such a react (ii) Stepwise reactions : In which the bond making and the bond breaking processes occur consecutively and two or more intermediates are involved. ‘The intermediates may either stable molecules capable of isolation, or highly unstable species of transient existence which may be called the reaction intermediates. If the intermediate isa stable molecule, the reaction may be considered as a multistep reaction consisting of two or more concerted or discrete steps. TheFundamentals of Organic Reaction Mechanisi ss 57 Carbon radicals may also be formed by the reaction of other free radicals. For example : 1. By the fragmentation or decomposition of a free radical—Benzoxy free radical decomposes and thus phenyl radical is generated. oe CoHp—C __ decomposition \ 0 2. By the abstraction of an atom from another species—Chlorine free radical abstracts an H atom from methane and thereby methyl free radical is formed. BO jes ee cu 8. By the addition reaction of a free radical to a multiple bond—When bromine free radical is added to ethylene, a carbon radical forms. additi CH)=CHy + Br" CH — CHBr By the rearrangement of another carbon radical—Neopentyl radical rearranges to tert- pentyl free radical. +CoHs+CO2 . in Ges atinanGED Sierras aver Gi CHy CH ‘Owing to the presence of odd electron, a carbon radical, like other free radicals, is paramag- netic in nature; for the same reason these are highly reactive. They undergo coupling reactions, disproportionation reactions and other redox reactions. Atom abstraction and addition reactions are also common to them. They also undergo rearrangement reactions which have already been discussed alongwith the formation of free radicals. Here we shall discuss coupling reaction and disproportionation reaction. Two carbon radicals couple to form a molecule—thus two methyl radicals unite to form ethane molecule : nn fe ae Hig. 4 CH, —diimetisation _, y4¢_cHy Ethyl radicals undergo disproportionation reaction in which one radical gets oxidised to ethy- Jene and the other gets reduced to ethane. - disproportionation CH3CH2 + (CHC eye ees (CH2= CH + CH3—CH3 A free radical reaction takes place in three steps; the reaction between methane and Cl in diffused sunlight may be represented as follows : J, Initiation—In this step a free radical is first produced, generally by thermolysis (action of heat) or photolysis (action of light) or by redox reaction. shot i Gh —Phetolysis oy. 4 Il, Propagation—In this step further free radicals are produced by the action of the first formed free radical. In this step a chain of reactions happen to occur if it is energetically favourable.Advanced General Organic Chemistry : . HCI CHa +c —— AC. * HyC +Ch ————_HyCCl + Cl CH,O—H +c. ————+ -CHOl. + HC! O—¢H, +0, ———— “OWe0 +O! ChHO—H +0) ———— ChH@ +HO! OHO: + Oly) ues CEO! Gc—H +o} ———> Choy FHC! : III. Termination step—Here further formation of free radical is stopped either by coupling or by disproportionation reactions : ‘CH, +CH; ————> CHs—OHs CH) +Ch ———+ CHs—Cl ‘CHCl +Cl ————> Cl;Ch ClHC: + Cl ClyHC ChC + Ch CCl, Therefore, a free radical reaction gives rise to a mixture of products. In practice, sometime: ‘we want to inhibit the propagation step; for this, inhibitors, i.e., substances which terminate | reactions are used. Phenol, quinones, diphenylamines, iodine, oxygen, etc. are generally us inhibitors. Triphenylmethyl radical produced by the reaction of finely divided metallic silver on triphenylmethyl chloride may be inhibited by the oxygen of the air. Oxygen is also an initiatc of free radicals. When propene is kept with oxygen, free radicals develop. Molecular oxygen is diradical; so it acts both as inhibitor and initiator. ; ‘The structure of the carbon radicals are very difficult to predict. They have planar to py midal structure depending on the groups and atoms attached to the C atom bearing the « electron. It is, therefore, assumed that such a © atom is either sp? or sp? hybri 7 percentage of s character of the C atom varies from 33.3% to 25%. For example, methyl radic is essentially planar; its C atom is considered to be sp? hybridized with the odd electron in the involved C atom is considered to be sp? h dised (Fig. 11.4). In the methyl radical bond bond pair interaction of electrons is stronger than the bond pair—tone electron interaction; whereas in the trifluoromethyl radical, the lone electron—bond pair interaction is stronger than bond pai pair interaction because of the high electronegati\ of F and the length of C—F bond (which is lo than C—H bond). Allylic and benzylic free radicals are also planar; the involved C ato: sp? hybridised. ‘The stability of a carbon radical depends on the degree of delo. As the delocalisation increases, the stability of the radical een a od electron may take place in two ways : (a) By hyperconjugation and (b) by conjugation, The stability order of the alkyl radicals, as given below, is explained by the hyperconjugati effect (see problem 4.20). “hai ms are supposed to be MegC > MegCH > MeCH, > CH;Aundamentals of Organic Reaction Mechanisms 59 As we move from the tert-butyl radical to met! ; hyl radical, we get decreasing number of no-bond resonati ing structures in their resonance hybrids and thus their stability falls down the series. ‘The stability of allylic and benzylic radicals are explained by the p ~ m conjugation as given below : (6 GL, — ou, crc = [CHy)=CH==OH,]’ Hy H—QH) ie, |Hy H— 1d fa We know that bond formation energy and bond dissociation energy are equal in magnitude ‘but opposite in sign. Table 11.1 also represents the bond formation energy of those radicals, High energy content means instability; hence radicals with higher energy are less stable than those with lower energy, A free radical may be detected by the study of magnetic susceptibility and electron-magnetic- resonance. Problem 11.1, Write down the stability order of the following radicals ; Benzyl, diphenyl- methyl and triphenylmethy!. Solution : The structures of the given radicals are as follows : Sa CyRICLO Benzyl radical __Diphenylmethyl radical ‘Triphenylmethy! radical The odd electron of each of the radicals can get delocalised by p— 7 conjugation because the C atoms bearing the odd electrons are in sp? hybridised state and Cs of the benzene rings are also in the same state, Again, as the number of benzene ring increases from benzy1 to triphenylmethy! radical, the probability of delocalisation of the electron over a greater range increases. We know that greater delocalisation of electrons means greater stability of the species. Hence stability order of the given radicals is ; PhCH: < PhoCH < Phy It is found that with increasing number of Ph group, the interaction between two ortho-H stoms of two rings increases. This disturbs the coplanarity of the rings though the three C-Ph bonds in the tri iphenylmethyl radical are very much planar; it has a propeller-like shape.vanced General Organic Chemis ( _ hich a C atom bears a positive charge an ium ions are positively charged species in w Since id ium ion may be represented as six bonded electrons, i.e., three bonds. Hence a carbeni 0, “h iid be followed by the wor. enium ion, the name of the group or groups shoul U To name a carbeniuum io group ee cation; or they may be named by the derived system of nomenclature as & & e e CHs CH3— CH2 (CH3)2CH Methyl cation Ethyl cation Isopropyl cation (carbenium ion) or Ce aan or Methylearbenium ion Dimethylearbenium ion or carbocation _ or methyl carbocation ; dimethyl carbocation f Problem 11.2. Write down the names of the following species : @Mxé ) [>—Gx—~<] GH) p> Solution : (i) tert-Butyl cation or trimethylcarbenium ion (trimethyl carbocation). (ii) Dicyclopropylmethy! cation or dicyclopropylcarbenium ion. (iii) Benzyl cation or phenylearbenium ion. Qe es Heterolytic cleavage of a bond gives rise to a carbenium ion. Heterolysis is carried out several methods : 1. By direct ionisation—In which a group leaves the substrate with a pair of electrons this case a highly polar solvent medium having high dielectric constant is required. T’ reaction is reversible, so the anion formed is to be removed. Ag*, Zn**, He*~, etc readily do the job. ‘Agt CH Br AgBr + CH 2. By the addition of acids to mutple bonds—Acids used may be either protic acid o lev aa H® e (a) CH2=CHz ——= CHs—CHz —(b) CH; C0 ICly @ me if (c) CH3C=N: CH3C=N— AICl; Addition of a cation to a multiple bond also generates a carbenium ion \ rey ig a ea —=C eee Vegans 1 eyFundamentals of Organic Reaction Mechanism 3. By the abstraction of an atom or Sroup using protic or lewis acids—In which a lone pair of electrons of the substrate coordinates either with the proton or with the lewis acid and then decomposes to a carbenium ion. : : “o (a) CHy-CH,—6—y Ee cree == CH: CH + H,0 H SbCl e (b) CHs—G == cH,—Ci—sbc1, ——= Crt, + sboiz 4, By the decomposition reaction—In which a species decomposes to produce a carbenium ion. Thus diazonium ions decompose and carbenium ions form. [% @ CHy-HN=N: —— CHy + Ny 5. By the rearrangement of a carbenium ion—In which a carbenium ion rearranges to produce more stable carbenium ion. Neopentyl carbenium ion rearranges readily. @ , @ CH;—C—CHy , CH; —C—CH; —+ CH; —C—CH,—CHy 2 a CHy CH CHy Neopentyl cation highlly strained Carbenium ions are short-lived species. They can accept electrons and hence may be looked upon as lewis acids. They undergo four types of reactions : 1. Combination with an anion—In which one often gets a stable product. Thus, when HCl is added to ethylene, first ethyl cation is formed which combines with Cl” ion to form ethyl chloride. H® 2. cr CH2=CH2 === CHs:CH, —— CH3CH2Cl 2. Elimination of a proton—In which a stable unsaturated compound is formed; for’ instance, isopropyl cation gives up a proton to form propylene. " CH3—C—-CH, ————> CH;:CH=CH) LY Ea 3. Addition to a multiple bond—In this case another cation is formed which then produces a stable compound by another reaction. x a xe Re + ——— _ $C—cHR 7 peop 4, Rearrangement reaction-*"It has already been discussed in the formation of carbenium fonsFundamentals of Organic Reaction Mechanism 513 eation and are thus called bridged carbenium ions or non-classical carbenium ion or, carbonium jon. 3-phenethy! cation is an example of non-classical carbenium ion : H —O— mompeacia: O GH, H26— CH, 5 < CHy—CH, Ha 2 CHy—CH, = HyC—CH; H,O— CH Bridged cations with delocalised bonding o electrons are called noii-classical carbeniumn i or carbocations which contain two-electron three-centre bonds. These are now called carbonium jons. Non-classical norbornyl cation forms as an intermediate when ex0- and exclo-norbornyl bro- sylates (brosyl group is p-BrCgH,SOz) are separately subjected to acetolysis in the acetic acid medium containing potassium acetate. Norbornyl cation then gives racemic norbornyl acetate though the two substrates, the (.c- and endo-forms, are diastereomeric. However, the former one HOAc/KOAc _very fast, OAc evAcO) HOAc/KOAc OO ay apy iawil,, mdo | OBs AcOH & |-OBs KOAc @ carbonium ion; norborny! cation Carbenium ion reacts much faster than the latter, and direct non-classical carbocation formation by the neigh- bouring group participation (Sec. 11.7.3) is said to be the cause for the very fast rate of the reaction. The ondc-isomer, under the same set of reaction conditions, undergoes the reaction but slowly. It is supposed that a classical carbenium ion forms first which then changes slowly to the non-classical carbenium ion before the reaction with acetic acid and potassium acetate. Bridge-head carbenium ions or carbocations are different from bridged or non-classical car- benium ions. C atoms at the junctions of a bridged ring system are called bridge-head carbons. When a bridge-head carbon bears a positive charge, it is called a bridge-head carbocation as ae Ord ©: rg, Chem.-33,Te Advanced General Organic Chemistr, Bridge-head carbenium ions are highly unstable since the cationic carbon cannot assume i, usual planar trigonal orientation of its bonds. However, (b) is less strained - less unstabje than (a); perhaps a six membered ring being more stable than a five membered ring, (b) is more stable than (a). Carbanions are anions, i.e., negatively charged species in which a C atom carries three bonds and a lone pair of electrons, thus making the C atom negatively charged. So a carbanion may by represented as | ee In naming a carbanion, the name of the group or groups should be followed by the word anion or these may be named as derivatives of methane : HC: CH-CH, CH-CH-CHs P Methyl anion Ethyl anion Isopropyl anion or or or Carbanion/Methide ion Methyl carbanion Dimethyl carbanion b Ne x CH3-CH2-CH-CH3 CH CH, eer : sec-Butyl anion Cyclopentyl anion Benzyl anion i) Ethylmethyl carbanion Phenyl carbanion Problem 11.3, Write down the names of the following species = (i) CHsCHCHe, (ti) (CoHs)s Solution : (iii) (CHg)2CH-CH. (i) Propyl anion or ethyl carbanion or n-propyl anion. (ii) Triphenylmethyl anion or triphenyl carbanion or triphenylmethide ion, ; (iii) Isobutyl anion or isopropyl carbanion. Like carbenium ions, carbanions can be generated by the heterolytic cleavage of bonds; the parallel with th g carbenium ions. 1 methods of generating 1. By the abstraction of an atom : Using a base in which a cation is removed. Rov R+xe Generally, protons are abstracted by the bases like, HO, ELO~, PhgC-, ete BH a (@) Gt CHO bad oL —> chy =0—5 2 HO H H HFundamentals of Organic Reaction MeChani$) Is, (b) COmEt-PH-COmBE FO. com —En—coyee LA. EtOH H ORt o\ A | $C Bie Bey BE Note : Atoms other than hydrogen are also removed. on PhiGorc + 2Na PhgGNa + NaGl H Na Na Perhaps this is an example of homolytic cleavage. 2. By the decomposition of anions : ‘Usually carboxylate ions decompose to carbanions. R ne R+ Co. alee No CH, a 8 GH + CO: Pech is + COp 3. By the addition of anions to a multiple bond : When highly electron-withdrawing groups are present on multiple-bonded C atoms, the latter atoms can add up anions and thereby carbanions can form : ESS ge aa ce HE, pé—cr.c1 poo RG # 4 BoP 4. By the rearrangement of carbanions : A less stable carbanion rearranges to a more stable carbanion. Ph {ec lee — Ph—C— CHpPh Phi Ph ‘A carbanion is capable of donating electrons to other species. Therefore, it behaves as a Lewis base. These are short-lived species. As an intermediate, a carbanion may undergo all the four types of general reactions. Amongst these displacement and carbanion addition reactions are ‘ery common; whereas carbanion rearrangement reactions are rare. 1. Displacement reaction : It displaces halogen atom from an alkyl halide and forms an alky- lated product. EOC. yO EtO2C~_ fs CH + CH SI —> CH-CHg +1 Et0,0~ Dee EtO.0~ie ens A dvariced General Organic Chon i., 2. Carbanion addition to a multiple bond : It is a very common reaction in the chemistry ie carbonyl compounds. R AN Yi \ @ | (a) cHy— 6” + RMgX ——— Ha —OMgxX Na H 9 (b) erg + CH: CHO————> CH '—CH* H H Aldol condensation reactions involve carbanion additions. 3. Elimination reaction : When ClyCHCFs is treated with alcoholic alkali a carbanion results ‘The fluoride ion then leaves the species and an alkene is formed. EtOH - Q OB faa CO Ory oe CLO=CF, + F- cc —cr, mace | 7 ROR i 4. Carbanion rearrangement reaction : It has already been discussed in the formation of carbanion. 5. Combination with cation : The most common reaction of the carbanions is the combination with cations, e.g., protons combine readily with them. NaOEt_ = He F,C=CF, + ECOH———> F,6— CF, 0Et "+ F,CH— CF,0Et The C atom bearing the negative charge in a carbanion is supposed to be sp® hybridised since it has a pyramidal structure like ammonia. In fact, it is isoelectronic with amines. The two unshared electrons reside in one of the four sp? A.O.s. The lone pair of es on © atoms of certain carbanions delocalise involving resonance and therefore, in those cases the C atom is definitely sp? hybridised and the lone pair occupies « A.O.. The stability of carbanions may be explained by I effect and conjugative effect, Alkyl anions have the following order of stability : ee Alky! onion: Cy > CH3CHz > (CHs)2 GH > (Cy), & This order can well be explained by inductive effect. +I effect increases th ity on the negatively charged C atom of an anion; thus as the number of methyl ee the anionic C the negative charge also increases on it and consequently the stability of the snev'es decreases. Therefore, the stability decreases down the series, The high stability of allyl and benzyl anions are explained by the conjugative effects. We know that the greater the delocalisation of negative charge, the greater is the stability, CH)=CH— GH, > &#, — cH=cn,Fundamentals of Organic Reaction Mechanism oer GH, CH, OH 6m, H I ea > —d) +l WA me Carbenes are very short lived species in which one C atom possesses two bonds and two electrons, either paired or unpaired. ‘The simplest member of the class is meth Isolable species of the formula HzC:; besides this, the most. common carbene iw :C formulae of a few more carbenes are given below: ¢, & now ‘The R,C=C=C:, — CoHs—C— Cos, He—O-—R oO Usually carbenes are named as a derivative of :CHy; thus :CCl, may be called dichlorocarbene and similarly diphienylcarbene is PhgC; CHs— CO—CH may be named as acetocarbene. ‘There are two main methods by which carbenes can be formed : (a) By elimination reaction ; Formation of dichlorocarbene by the action of alcoholic KOH on chloroform is an example of this method. This may also be obtained from trichloroacetate by the process of thermolysis. alc. KOH heat CHCl; ————— c,¢: ———"____ ¢c1,c00: * S=HCI 2: 00, & Cr (b) By decomposition reaction : When diazomethane or ketene are pyrolysed or irradiated with ultraviolet light, they give rise to carbenes : heat heat ® CH,=C=0O eens :CH ay CH y= N= N: The two non-bonded electrons of a carbene may be either unpaired or paired. When these are unpaired, the carbene is said to be in a triplet state (spectrally). If they are paired, then the carbene is called singlet (’triplet state’ indicates two unpaired spins, whereas ‘singlet state’ to paired spins) carbene. Both singlet and triplet carbenes have bent shape; bond angles are around 103° and 136° respectively. There are a few singlet carbenes which have resonance stabilisation involving atom with unshared pair of es as shown in the next page. fers ‘Vacant pA.O QP, hybridised 103° (SC<>—sp? A.O we Ree ‘sp? hybridised ‘a0? singlet carbene triplet carbene ed to be in the 4 bond angle is At least in the above cases the C atom holding the lone pair of es is sp? hybridised state and it has a vacant p A.O. for back bonding. So, the expeFundamentals of Organic Reac (b) Addition ; Both the singlet and the triplet carbenes undergo addition reactions to a multiple bond. The addition of a singlet carbene to a multiple bond is a stereoselective and a stereospecific reaction. The addition is syn, When cis-but-2-ene is reacted with chloroform in the presence of potassium (ert- butoxide in the liquid phase, cis-1,1-dichloro-2, 3-dimethyleyclopropane is obtained; under the same set of conditions, trans-2-butene gives trans-1 1-dichloro-2, 3-dimethyl- cyclopropane. Cs CHa cHotyKoBu() His, ae) ae ie ee He” Na in solution cis acl Fg AHS __ CHOWy/KOBu (t) ee x cis cH” ONa in solution trans \, ch 23 cl Cl a a KOBu (t 2 ECEmS Ge ee) Gre 4 enon =o Soe Kal sine. ip a In this step through an a-climination reaction on chloroform a singlet dichlorocarbene is formed. The electron-deficient:( i.e., electrophilic) CCl, accepts 7 electron of the alkene in its empty orbital and donates its lone pair of es simultaneously to the more cationic C atom of the two double bonded carbons and those become partially positively charged in the T.S. CHa ACH3 :CCl, _ CHgm9*__9* CH CH gia aCHy rare Sei HH > pe C—O \ aa cis product cis compound cis addition Ha a, ACH3 _:CCly oun ica Cl trans compound cis addition TS. trans product A triplet carbene undergoes radical addition reaction with a C—C multiple bond since it is 4 diradical. It is generated in the gas phase in situ by the process of photolysis on a mixture of diazomethane and alkenes; the latter compounds are the substrates for the addition reactions. CHa aC jo, Hama, ; CH = eae na : ot + Znl, /\ HOH cis at CH See 'CHy H + Znly i \ Cis-addition ft trans In some cases carbene addition product undergoes the ring expansion reaction. cow " 5 C ; S + sor ake aly Ses ME et lee N Ww NG A t singlet Ao COsEt CO.Et CHN,CO, E: —4—+ ‘SHCO,E ———_ A ey singlet > Hs From ring addition products several other compounds can be synthesised. e.g., CH3HC. HCH, | CHjHC——CHCH, CHjHC——CHCH, Big bom 4 si Bias, =H,0 db f HO OH Carbenes undergo rearrangement reactions and stable molecules are obtained. In these reac- tions migration of alkyl groups and H atoms generally takes place. i) a2 ‘CH ——— CH;—CH=cH,Yy Advanced General Organic Chemistry ai (ii) es Oo i Gu. 0= =CH—CH, Triplet carbenes also take part in abstraction reactions and thus form free radicals, c.g methylene reacts with ethane and produces methyl and ethyl radicals. CH, —GH> maa ° Il ein Il (ii) Pyrolysis: RC—N=N=N: ——— RON + Np Acylazide ®@ bs ry (iii) Photoysis: H—N— ; em Nem Hydrazoic acid & by, 4 FNC Oe ee ee GG Alkyl isocyanate=. ‘undamentals of Organic Reaction Mechanism, eo Huotion method + When compounds containing —-NH group are oxidised with lead tetraacetate, activated mercuric oxide, manganese oxide etc., nitrenes are ob- tained. Aromatic nitro and nitroso compounds on heating with (tO), P (triethyl phos- phate, a reducing agent) give nitrene. Z Z Ke | Oo SS EtO)3P FOP | a Arno, OE yg —OHP any ‘There are two types of nitrenes ; triplet nitrene and singlet nitrene; triplet is the ground state of nitrene since two degenerated orbitals accommodate one electron each. A singlet nitrene has both the electrons in an orbital. Nitrenes behave as electrophiles and they undergo usually addition, insertion, rearrangement and H-abstraction reactions. (a) Addition reaction : Nitrenes add to the C=C double bond Be GHp (i) HN +I x] CHy (ii) + PhSO..N N-$O2-Ph ok (iii) CH,=CH— CH=CH, + H—] ——— N—H ne—Ctt, (b) Insertion reaction : Nitrenes are found to undergo insertion reaction in C—H bonds : | ef | Ria ee aoe (c) Rearrangement reaction : The most easily formed nitrenes usually rearrange : Alkyl isocyanate Note : This is a proposed step in Hofmann, Lossen and Curtius rearrangements; perhaps the formation of nitrene from RCONHBr and its rearrangement to alkyl isocyanate are concurrent steps and no free nitrene forms, but it has been argued that nitrene exists for a short time in the acid-catalysed Lossen rearrangement.= mms Advanced General Organic Chemist, mes; the simp) 1,2-dehydrobenzene, CoH,, and its derivatives may be called benzynes or member is benzyne (Fig.11.5). It is a non-isolable highly reactive species. Benzyne has hexagonal planar ring structure with six delocalised electrons and two othe; additional x electrons in a 7 orbital formed by the side-on overlap of two sp” A.O.8 (containing one electron each) covering two C atoms only; this bond orbital lies along the side of the ring ang creates deformation of the bond angle (120° to 180°) (Fig. 11.5). The deformation of the bong angle causes a strain and makes the species high!y reactive. Its structure may also be looked upon as a resonance hybrid of some resonating struct (Fig.11.5); dipolar structures explain the electrophilic character of benzyne and the six-membered ring structure containing a triple bond explains the instability and hence the high reactivity o: the species. Thus the structure tells us that these two additional electrons do not interact with the x cloud involving Huckel number of x electrons and hence they do not affect the aromaticity of the benzyne molecule. ‘There are four important methods for preparing benzynes : } (i) When halobenzenes or their derivatives are treated with metal amide ion in liquid ammonia benzynes are formed. a NH2(Na®NH} ) in liquid NH (ii) Thermal decomposition and photolysis of the diazotisation product of anthranilic acid i: benzene give rise to benzyne : coo CoHs | a; i? Roe la + COz (iii) When o-dihalobenzene is treated with lithium-mercury amalgam, benzyne F C=O Br (iv) Benzynes can also be prepared by the action of phenyllithium, OCH SCH, F CoHsLi |of Following properties of benzynes are discussed below : (i) Benzynes being electrophilic, they undergo nucleophilic addition reactions . NH, NH, Bees ieee NH ‘y S NH, (ii) Benzynes undergo 14-addition to conjugated dienes CS— oo The transient existence of benzynes as intermediates is detected Spectroscopically and by trapping them, i.c., making them react with conjugated dienes and isolating the products Nowadays a number of syntheses are done via benzyne; e.g., one can prepare pheny! benzoate from anthranilic acid via benzyne formation « coo CoO 0. to) on NHO, Cx heat OQ CeH;COOH CY N\A onl eee OURS ; NH Na CoHs Biphenyles can be Prepared by the action of phenyllithium. OCHs OCHs OCHg OCH, B= 5-8 50 For detailed reactions of benzynes consult aromatic substitution reaction nucleophilic via arynes (Chapter 12). A weakly bonded charge-transfer complex which association of an electrophilic species (E) and an electron-donating Species (D) which utilises its x orbital electrons for association is known as a -complex. Arenes, alkenes, alkynes, cycloalkenes ete., are the electron-donors and metal ions, molecular halogens, hydrogen halides ete. are the common electrophilic reagents, For example, at 78°C toluene forms a1 ; | r-complex with HCl alone, Similarly ethylene forms @ m-complex with silver cation (Ag®). ‘The structure of a x-complex is not completely known. It is supposed to be a resonance hybrid of the following Tesonating forms ; n only and is formed by the s ee oe es +B+-————. D— 8. D—E a b e oy D+E wee D.Fundamentals of Organic Reaction Mechanism LL |) density in the donor species and electron-withdrawing groups which decrease electron density in the electrophile increase the st ength of the x-complex. In a n-complex the distance between the two planes of the components is usually 0.3 nm to 0.35 nm. If either component is non-planar, the Gitanee between the planes increases, wlyich decreases the atractive force and thereby decreases the stability of the complex. P N.B. : Charge-transfer complexes may exist in solid state or in solution. In such a complex the donor component may utilise its wes or nes to form the complex. Thus a 7-complex is a charge-transfer complex but a charge-transfer complex is not always a -complex. When an electrophile reacts with an arene usually in the presence ofa catalyst, a sat is formed, This salt is composed of an anion and a complex resonance stabilised carbeniuma fon (arenium ion) in which only two of the total es, which are required for preservation of the aromaticity of the arefe, are utilised to form a o-bond between a particular C atom of the ring and the electrophile; Such a salt is called a o-complex salt and the carbenium ion is called a o-complex or Wehlurg, intermediate, For example, when benzene is treated with HCI in the presence of anhydrous AICly, 8 Lewis acid, a salt of benzenium ion and AlCl, the o-complex salt, is formed. H— C—E oiety of a o-complex lies on a plane perpendicular to the plane of other ting earbons as given below. E H A o-complex is a resonance hybrid of several be represented as a resonance hybrid. He HH He HH Hi HH Fvge > > eH + HCl + AlCl; —— — | | — AIC, e H Tesonating structures. The benzenium ion may wo Nae a eeFundamentals of Organic Reaction Mechanism 529 while the coupling product of a sigma-complex is not an aromatic compound. An aromatic com- being more stable than a non-aromatic compound having double bonds, -complexe: ‘up proton to gain stability. For example, A gives nitrobenzene by giving up a proton. NO, NOr 4 f NO oy B90, 2 om Baie + 1,80, i A a-complexes undergo isotope exchange reactions. When benzene is treated with DCI— AICly, there is an exchange of deuterium for hydrogen—CgDg has been prepared by this method. The stability of a c-complex mainly depends on three factors : I effect, R el perconjugative effect. An arenium ion being a positively charged spec and hyperconjugative effect of alkyl groups increase its stability; while —I effect a decrease it. If a group with +I or +R effect is situated at the o- or p-position instead of the m-position with respect to the tetrahedral C atom, the c-complex gets extra stability. For example, c-complex B is more stable than o-complex C. H®CH) CH CHy CH 4H i oH 4H B X es anes X ete. e Z H He a CH CH, CHy aa H it een (= Seage X NS x x WH a H ne H ‘Thus in B the positive charge gets further delocalised by the hyperconjugative effect of the methyl group; whereas in C there is no such effect. We know that the greater the delocalisation of charge, the greater is the stabilisation. So B is more stable than C. Similarly, D is more stable than B : Zim) ‘OH ‘0-H 6-H ‘O—H] | D e eee pel ‘ea ON X Ho Nx oS HY” YX HY xX |x-SRS 5-5 Ea bile H Beier i ore nic venttions are censraly Gabaiéd ualer three heads; (a) electrophile and (b) nucleophiles and (c) radicals. There are ambident nucleophiles and electrophiles also. eee ental 11.5.1a. Electrophiles Electrophiles are electron seeking species. They seek electrons because they are electron- deficient species. Therefore, they accept electrons from other species; for this reason electrophiles are also called electron acceptors. A particular site of an electrophile is generally found to be electron deficient and that site is called electrophilic site. Electrophilic sites are of three categories: ® ee 6 (i) They may have positive charge : NO, H, NO, R3C, (ii) They may have less than 8 es in the outermost shell of the electrophilic site such as : B of BFs, Al of AlCls, (iii) They may be the positive pole of a polar bond : b+ b= b+ I—c CH;—C—H oeYY ne Advanced General Organic Cheri, ty ‘As electrophiles accept electrons, they may be looked upon as acids. Again we know 1),,, species gets reduced when it gains electrons and thus serves as an oxidising agent. Theres, * electrophiles may be viewed as oxidising agents. The capacity of an electrophile to accept an electron pair from a standard donor may be call its electrophilicity. Electrophiles being highly reactive transient species, the exact order of i)... electrophilicity has not yet been determined. The following gives an highly approximate ord, @ Cl® > Br? > NOP > Ch = I® >> Br > NO > PhNP >> He® > be 11.5.1b. Nucleophiles Nucleophiles are nucleus seeking species, because they have electron~ electrons to electrophiles and hence nucleophiles are called electron donors. may have : (3) Negative charge : OH, OR, RCOO-, H-, RS~ rich sites. They donat, Nucleophilic sites (ii) Unshared pair of es : bo éba b- s+ (iii) Partial negative charge of a polar bond : R——MgX, R —Li (jy) 7 electrons : Benzene, naphthalene. Nucleophiles being electron donors, they may be looked upon as bases and reducing agents. ‘The reactivity of a nucleophile may be called its nucleophilicity. Both a base and a nucleophile are electron donors. It seems, therefore, the basicity order of a set of electron donors is their nucleophilicity order; but this is not always true for the reasons given below : (i) A base coordinates mainly with a proton whereas a nucleophile coordinates with an ator: other than proton and very often with carbon. (ii) An acid-base reaction is an equilibrium controlled, ie, a thermodynamically controlle¢ reaction whereas an electrophile-nucleophile interaction is a rate controlled, i.e. kinetically controlled reaction. However, nucleophilicity depends on many factors as given below : (i) Basicity, (ji) Polarisability, (iii) Solvation, (iv) Nucleofugacity, (v) a effect. To understand the nucleophilicity order among a set of nucleophiles the following rules, which are related to the factors said above, are discussed : 1, Basicity and Nucleophylicity : a, Under a given set of reaction conditions a nucleophile with an anionic attacking atom is more nucleophilic than its conjugate acid which is also a nucleophile. Thus OH is more nucleophilic ies H20 and NH; than NHg. Here the basicity order and the nucleophilicity order are one an‘ e same. HO: > HzO; H2N:- > NHs b. In a set of nucleophiles having the same attacking atom, the nucleophilicity increases 2 the negative charge density on the said atom increases, i.e., the basicity increases: ClO; < H20 NH2 > OH > F- (ii) RsC~ > R2N- > RO- > F- 2. Polarisability : The greater the distortion of the charge cloud of the valence electrons around the attacking atom of the nucleophile by the electrophilic centre, i.e., the greater the polarisability of the attacking atom, the greater is the nucleophilicity. Again the greater the volume of the attacking atom, the higher is its polarisability. For example, the nucleophilicity of PhS” is higher than that of PhO-; but this is not always true, From the point of polarisability the nucleophilicity order among halide ions parallels their order of volume only in a protic solvent, ie. IX > Br~ > Cl” > F~. Actually nucleophilicity depends on solvation also. 3. Solvation : In a protic solvent smaller groups with higher charge density become more solvated than larger groups with less charge density. The smaller groups being strongly solvated, they are less free for attack than the larger groups which are more free being less solvated. The more freer the nucleophile, the more higher is its nucleophilicity. In a protic solvent, the degree of solvation decreases down a group. So F~ is the most solvated nucleophile and I~ is the least in a protic solvent. Therefore, from F~ to I, in a protic solvent, solvent effect decreases, i.e., freeness increases and polarisability increases; and the nucleophilicity order is I~ > Br~ > Cl- > F~. In an aprotic solvent none of them gets solvated (see Ch. 7). Hence alll are free to move. So, the charge density order is F~ > Cl- > Br~ > I~ and this is also the nucleophilicity order. 4, Nucleofugacity : If in a reaction the leaving group of the Substrate is electron dense, it is called nucleofuge. The ability of mucleofuge to leave the substrate in a reaction is called its nucleofugacity. As the nucleofugacity increases, the C atom bearing the nucleofuge becomes more electrophilic and its ability to polarise the incoming nucleophile also increases. The more polarisable nucleophile, therefore, gets polarised more and its nucleophilicity increases. In general a highly polarisable nucleofuge is most readily displaced by a highly polarisable nucleophile. For example, the rate of the reaction between pyridine and ethyl iodide is 5.75 times faster than that between pyridine and ethyl bromide; the mucleofugacity of I~ is greater than that of Br~ from the consideration of volume and polarisability. Similarly, reaction A is 31 times faster than the reaction B as given below : QE+E—_r —— 1l—Et +I; (B) I-+ Et— Br ——— I—Et + Br- 5. o-Bflect ; It has been found that if there is a lone pair of electrons on the a-atom with Tespect to the attacking atom of the nucleophile, the nucleophilicity increases. The basicity of hydroperoxide ion is 10 times less than that of OH because of strong —I effect of HO group in HO— 0-, but HO— 0, the hydroperoxide ion, reacts with monobromoacetate 20 times faster than OH because the mucleophilicity of the former is greater than that of the latter.tals of | i ion oar eeteteeeeneraenemeaaaineeetineetaneee Fundamentals of Organic Reaction Mechanist? ____«_1- 5:5 Furthermore, a nucleophile with a negative charge on the attacking atom is harder than its conjugate acid. Thus NHp > NHy, OH > Hy0 and HS~ > HS. Again, © positively charged carbon is a harder centre (electrophile) than a partially positively charged! carbon, while the latter is a harder electrophile than a neutral or less partially positively charged carbon, Thus increasing softness 9 a) Il ort eal Dey Ok jot man Gs 3 where d+ > dy+ - ons S decreasing hardness Let us now discuss hardness and softness actions in the light of Frontier Orbital Theo: a chemical species is called HOMO. (Highest orbital of the lowest energy is called LUMO of electrophiles and nucleophiles and their inter- ry: ‘The occupied M.O. of the highest energy of Occupied Molecular Orbital) and the unoccupied (Lowest Unoceupied Molecular Orbital). When nucleophile-electrophile interaction occurs, the most effective interaction is that between the HOMO of the nucleophile and the LUMO of the electrophile, So, HOMOs and LUMOs are called the frontier orbitals. When two chemical species collide, the orbitals of one reactant overlap those of the other and the energy gained or lost (AE) by the interaction may be expressed as: AE=Evore + Eelectrostatic + Eoverlap, (4.1) where Exoro= + ve, this arises owing to repulsion between occupied orbitals of the two species. E, ‘electrostatic —~ ve, this arises owing to the attraction of any + ve or — ve charge on one by any ~ ve or + ve charge respectively on the other. Eoverlap= ~ ve, this arises owing to the overlap of occupied orbitals, especially the HOMO, of one with unoccupied orbitals, especially the LUMO of the other. Here it is needless to mention that the negative AE value leads to the effective interaction. An electrophile-nucledphile interaction is also governed by However, a hard nucleophile has a low energy HOMO and usually a negative charge on the attacking atom; whereas a soft nucleophile has a high energy HOMO but it may or may not have ‘negative charge on the attacking atom. A hard electrophile possesses a high energy LUMO and usually a positive charge. On the other hand, a soft clectrophile has a low energy LUMO and it may or may not have a positive charge. the above expression. A hard-hard interaction is strong and fast because it contril term of the expression whereby AB becomes because of the large contribution to the E, ibutes largely to the EB, electrostatic negative. A soft-soft interaction is strong and fast ‘overlap term which again makes the AE value negative. Eoyeriap term will be large when a symmetry compatible HOMO and LUMO, which are close in energy of the nucleophile and the electrophile respectively, interact, 11.5.1d. Ambident nucleophiles “Ambi’ is a prefix occuring in loan words from Latin where it meant ‘ambiguous’ (uncertain) and ‘dent? means tooth. ‘Therefore, an ambident nucleophile is a species which has two (or more) different or similar types of nucleophilic centres through which it can attack electrophilic centres. » nitrite and enolate ions are-the examples of ambident nucleophiles.Fundamentals of Organic Reaction MCh, TD: 537 Now the question is : are really the behaviours of the ambident nucleophiles ambiguous? The answer is; no. Let us now examine the answer from the standpoint of the hard-soft nucleophile- electrophile interactions as discussed in section 11.5.1¢. In each case of the before-said examples {a,b and c) the reaction involves either a hard-hard interaction or a soft-soft interaction. The hard and soft centres of each nucleophile are labelled here following the fact that the hardness increases along a period from left to right hard soft cent oN, er centre C=N: Ne | 5520. 6-0 he os 7 \ hard centre soft centre Ambident nucleophiles labelled as hard and soft centres ‘The C atoms of CHsBr, CHsI and RCHaI are the soft centres. So, CN~ and NO} attack the electrophilic Cs through soft centres, C and N respectively and we get methyl cyanide, ni- tromethane, etc. as major products. When potassium cyanide and sodium nitrite are the reagents, 1° and 2° alkyl halides react with nucleophiles without having carbocation generating counter part (Ag®, Hg®® etc.) in the same way as methyl halides. In the presence of Ag® or Hg®®, which are generated from the reagent AgCN, AgNO», HgCl, etc. as shown below, 1° and 2° alkyl halides become more carbenium ion-like in which cationic carbons are hard centers (being appreciably positively charged). So the nucleophiles attack the cationic Cs through hard centres (N of CN~ and O of NOj) and naturally the major products are alkyl isocyanides and alkyl nitrites. ‘AgCN=— AgCN —+— Ag® + CN-; AgNO. Ag® + NOZ solid in soln. in soln. in solution oe :C=NF CHy-“Br + Ag? ———> C=N—CH, + AgBr | rps Daa Po Rone-41 + Ae? —— 0= 6} \—O— CHR + Agl | 11.5.1e. Ambident electrophiles @, G-unsaturated carbonyl compounds are ambident electrophiles. For example, in ol Il MeCH—= CH—C—Me there are two electrophilic centres. They are 2 ea 4 positions. i { sald MeCH=CH—¢— CH Ph Mecu—cu—l—Me _ Me 1, MegCuLi ee on, 2. H0° MeFundamentals of Organic Reaction Mechanism reece mnt: er er With respect to the O-, a hard nucleophilic centre, the electrophilic C atom of acetaldehyde is a soft centre; a hard-soft interaction being weaker and slower than a soft-soft interaction, the anionic C of the enolate ion attacks the electrophilic C of the acetaldehyde and 3-hydroxybutanal is formed and no hydroxyether is formed by the hard-soft interaction. ‘This reaction may also be explained from the thermodynamic stand point, In this reaction an aC—H bond and the x bond of the C=O bond are broken, whereas a C——-C and a O—H bonds are formed. The calculated heats of reaction (in kJmol-) are : NaOH qe iat pense go. —- aan tant g CeeO H H H 78.9 + 413.2 — (463 + 345.8) kJ mol~! 16.7 kJ mol! x : 378.9; HO—H : 413.2; 4HO—H ; 463, 4FC—C : 345.8; “C—O, = 358; *#C—C, = 264.6 (in kJ mol-!) NaOH gertan.| =0 CH;CHOH— O— CH=CH H AH = 2 x 378.9 + 413.8 — (463 + 358 + 264.6) kJ mol~? 85.4 kJ mol“? So, 3-hydroxybutanal formation reaction is exothermic to the extent of 16.7 kJ but hydroxy- ether formation is endothermic to the extent of 85.4 kJ. Hence the hydroxyaldehyde formation is thermodynamically more favourable than the hydroxyether formation. The ease with which a substrate or a reagent reacts may be called its reactivity. ‘The the reactivity of a reagent or a substrate, the higher is the rate of the reaction. A substrate may have different reactivities at its different sites. In isopentane there are 1°,2° and 3° carbons and hydrogens and the reactivity order towards halogen radicals amongst three types of hydrogens is 3° > 2 > 1°. On the other hand, chlorine radical is more reactive towards a particular type of hydrogen in isopentane than bromine radical. This means a chlorine radical reacts faster than a bromine radical and therefore, the reactivity of the former is greater than that of the latter. However, when we compare the rates of reactions at different sites of a substrate with the same Teagent, we consider it as a problem of orientation though different sites have different reactivities. ‘The comparison of rates of reactions of chlorine radicals on different H atoms of isopentane is the problem of orientation. When we compare the rates of similar reactions at similar sites involving Gifferent substrates and the same reagent, we consider the reactivities of different. substrates. If the substrate is the same but reagents are different, the comparison of the rates means the comparison of the reactivities of the reagents. igher i, s oe “CH,—¢——CH,— CHs “CHsFundamentals of Organic Reaction Mechanism ee 5 | However, the postulate tells us tl ordinate varies with the relative changes in a continuous manner solvent, catalyst, etc. In fact, to | be considered mainly : (i) Relative energies of the Teactant, T.S. and product (Sec. 6.6) (ii) The Hammond postulate (Sec. 6.4.2) (iil) The effect of catalyst (Sec. 6.3) (iv) The effect of solvent (Sec. 7.7.5) hat the position of the T.S. of a reaction on the reaction co- energies of the reactants, T.S. and products and the position as their energies are perturbed by the changes in structure, ‘cate the T.S. on the energy curve the following things are to (v) The kinetic control and the thermodynamic control of a reaction (Sec. 6.7) (vi) The selectivity reactivity principle (vil) The microscopic reversibility principle (vill) The neighbouring group participation. Since (i) to (v) have already been discussed in the sixth and seventh chapters, we shall discuss here the last three topics only. The principle states that : the more reactive a reagent, the less selectivity it reacts; and th less reactive a reagent, the more selectivity it reacts. ‘This means a highly reactive reagent will react indiscriminately and randomly with different. substrates in a reaction, whereas a less reactive reagent will differentiate between two or more substrates in the reaction and will react selectively. When the reagent is highly teactive, its energy content is very high. Though the substrates are different, yet the energy of the reactant side will be high since the energy of the reagent is high. In this case the different T.S.s for different substrates will be relatively early and reagent-like insofar as Hammond’s postulate is concerned; furthermore the different T.S.s wil dissimilar in energy. When the reagent will attack attack randomly and the T.S.s for the different sites will differ in energy but to a small extent. Therefore, in both the cases, in the cases of diffe rent substrates or sites, the rates of formation of different products will not vary appreciably. The reagent will thus show low selectivity. ill not be very different sites of the same substrate, it will also TS 04) *~Barly reagentlike Reaction coordinate — Fig. 11.8. The selectivity reactivity principle havotving # different sites of the = een oof ese same substrate lending to two ‘sobetrates of to \flereat products, X, and Xy. The two TS. are sbetrate Leading to two dierent proto. ‘carly and reagent-like and differ from each other in 3, and, Tis have appreciate ‘energy to 2 small extent a energy and they are ae and proFundamentals of Organic Reaction Mechanism LLL cular rearrangement, the participation is known as neighbouring group participation. Usually the neighbouring group remains on the 3-C, but it may remain farther away and in this case the comes near to the reaction site owing to the zig-zag nature of the carbon-chain, However, NGP is defined as the direct interaction of the reaction site with the lone pair of es of an atom or with @ or m es which are already present in the substrate molecule but not conjugated with the reaction site. NGP develops cyclic T.$.s or intermediate ring structures—3,4,5,6 membered rings are common; 5 and 6 membered rings are the most stable, CH, CHy CH3 CH; H—— 0H oe HO HBr H Br | Br H Bert —H H——Br Br H H Br CHy CH CHy CHy (+)-or(—)-threo forms (+)-threo forms CH CH CH; CH; H OH |. HO HuBr oH Br) Br set i Br Br A H Br Br H CH, CH CH (+)-or(—)-erythro forms CH erythro (meso) forms ‘The reactions between 3-bromo-2-butanols, active threo and erythro forms, and hydrobromic acid are one set of the classical examples of neighbouring group participation, ‘The active threo form of the alcohol gives only (-:) 2,3-dibromobutane on treatment with hydrobromic acid; while the same reaction with active erythro form gives pure meso product. Thus we see that the reactions have taken place with retention of configurations. ‘The retention of configuration in this reaction is well ex; participation as shown below : In this case Br atom is the neighbouring group of the reaction site C2(OH) of the substrate 3-bromo-2-butanol. The removal of the OH as HO has taken place through the bridged bromonium ion with inversion of configuration;. this is followed by Br- Cs atom and cleavage of the bromonium bridge with inversion of configuration. plained by the neighbouring group formation of the attack on C2 or Hs Me @ Me H Br Bré 0 Br aon —— Br M aie oH ‘one of the af threo forms Br. on H Meone of the erythro forms E K ‘Thus double inversions give rise to retention of configuration. In this case we see that a fi he Br atom and the Cz atom. This is not covalent bond formation has taken place between tl : all the necessary requirement; there are examples where only partial bond forms. However, the following are some of the neighbouring group participants : COO-, OCOR, COOR, OR, OH, O~, NH2, NHR, NR2, NHCOR, SH, SR, S C=C, Ph, H(rare). NGP is designated by specifying participating group and the ring size. The reaction betww HBr and 3-bromo-butan-2-ol is designated as (Br, 3). Now, the question is : what are evidences in favour of the neighbouring group particiy mechanisms? The answer is : only in the case of neighbouring group participation wit! arrangement one can get the direct evidence; in other cases, stereochemical criterion retenti of configuration and manyfold enhancement of rate over what might be expected normally «« the evidences. The enhancement of rate of a reaction involving neighbouring group participativ is called anchimeric assistance (meaning partaining to the adjacent part; Gr. anchi and m For example, the conjugate base of the -(p-hydroxyphenyl)ethyl bromide undergoes et a1 sis about 106 times faster than 3-(p-methoxyphenyl)ethyl bromide; the enhancement of r attributed to the anchimeric assistance of the p-phenoxy group. Br, | II (p 545) is much less stable than I because of + charge on the O atom, So in this cas effective bridged species forms. mb CHy—CHz—O—-H —CHCHOEt EtOMe OMe BLOH cs Seam yl O eS @ CHyCH,OBt CH,CH,OFt H _ Now we must get an explanation for the enhancement of rate in an anchimeric assistance In a chemical reaction, the reaction site and the reagent: require collision with each other. ‘The probability of such a collision in this case is less than the availability of the neighbouring group to the reaction site. Furthermore, in a bimolecular or termolecular reactions, the T.S. involves 2 or 3 species respectively and therefore, in such a reaction the entropy decreases reasonably. On the other hand, in a neighbouring group mechanism since the neighbouring group attacks the reaction site intramolecularly, the ‘T.S. does not involve any spe than the substrate ‘and therefore, entropy decreases but to a little extent owing to conformational reason. Here it ie needless to mention that a reaction with or without NGP has the same AH! when NG and the Therefore, AS! is the main criterion ‘Whether the rate of a reaction increases due to Anchimeric assistance or not can be ascertained by comparing the rates of the reaction of a substrate with and without the neighbouring group. If the rate of the reaction with the neighbouring group is many fold more than that of the substrate without the neighbouring group. neighbouring group participation may be considered. _ However, neighbouring group participations are found in addition, elimination, rearrangement ‘and substitution reactions as shown below @ OH) -HOCH,CH,Br HBr, ¢H,—cH, —— rota — BrCH,CH,Br BY Br: cy -c-. 8 6+ Guo! —2> ELN—CH—Et pq- EtN—CH—Et Ke oa i ‘CH Cit ou® TS. | Ety)N—CHCH,OH BtYY Fundamentals of Organic Reaction Mechs! as 557 mechanism is not also possible by a single experiment or by a set of experiments. However, the following are some of the methods generally applied for determining the reaction mechanism. Usually a number of products are formed in an organic reaction, one or two of them are it. Whatever may be their yield, large or small, any proposed mechanism should account for all the products and their proportions. If the mechanism fails to predict the products and roughly their proportions, it cannot be taken as a possible mechanism. When aromatic nitrocompounds are treated with cyanide ion, the nitro group is displaced and a carboxyl group ortho to the displaced nitro group. The products of the reaction was supposed to be NO, NHg and carboxylic acid. Since ON~ is the reagent and aryl cyanide gets hydrolised under the reaction condition to carboxylic acid and ammonia, AtCN was considered to be the reaction KP CO:H 3S + Ny (Von Richter reaction) 28 Br Br one Crr xo H cS TN Nye H ‘C=N c=n —H® si al or Oe SNi _—_—_—————s Advanced General Organic Cy, iy intermediate. Now it is found that besides NOz and NHs, molecular nitrogen is formed. 1, , found that not the NO but No is the major product of the reaction. To substantiate those; a quite different mechanism, has been proposed for the reaction which does not involve Aron an intermediate. The reaction is known as Von Richter reaction. Its mechanism is given ;, ‘ page 545. ‘Therefore, the isolation of products, the elucidation of their structure and determinati, their proportions give much information about the mechanism of a reaction. Nowadays gene, the products are isolated by chromatographic processes and their structures are establish spectroscopic methods and from their syntheses. By using isotopes many information about reaction mechanism can be obtained; some of t, are given below : (a) Whether a particular bond in the rate-determining step breaks or not. (b) Whether exchange of an atom (or a group) takes place or not. (c) Whether a reaction is reversible or not. Whether a particular bond breaks in the rate-determining step or not can be determined i studying primary kinetic isotope effect. We shall discuss this in the next section. 0 Which bond breaks can also be determined without kinetic study. There are two (— @ bonds in an ester molecule, one is acyl-O Paar bond and the other is alkyl-( Pate Ore bond. a oO 18 Which of the two bonds breaks when an ester is hydrolysed is determined by using H,0. I the acyl-O o bond breaks, '*O atom will be found in the acid (RCOOH). On the other hand, if alkyl-O ¢ bond breaks, the alcohol (R’*OH) will contain the 0 atom. The ester is hydrolysed using Hz'*O. The acid and alcohol formed are isolated and one of them is subjected to ma spectrometric study to detect the presence of 80. If it were otherwise, then !8O of H2!80 woul not have appeared either in the acid or in the alcohol. Here isotopic exchange may also ta! place. Whether a reaction is reversible or not can be determined by isotope exchange reaction. Wh a. compound having active >CHz group is treated with NaOEt in the presence of EtOD, deuteriuo is exchanged. For example, when ethyl acetoacetate is treated with NaOEt, a carbanion form To determine whether this reaction is reversible or not, this is carried out in the presence of EtOD. Now by mass spectrometry if it is proved that deuterium substituted ethyl acetoacetate is als present in the reaction mixture, it goes beyond doubt that the reversible formation of carbanict has taken place and the removal of H® from active methylene group is a reversible reaction OEt EtOD CH3COCHDCO,Et CHsCOCH2CO2Et CH;COCHCO.Et Besides non-radioactive isotopes, radioactive isotopes are used to obtain information abou thechanism. The generally used radioactive isotopes are 9H, '40,3P,35§, ete. Thus when labelle! chlorobenzene, in which Cl atom is held by “4C atom, is treated with NaNH in liquid ammonis, the product is aniline—50% of the product contains NH group on 4C atom and the other 50"Fundamentals of Organic Reaction Mechanism ins that on 12C_ si i azine reason. This information proves clearly that the reaction is not a simple case i ‘action and that there must be a reaction intermediate. sn Ni ‘ Nig NaNH2 in NHg(I) * indicates “C atom mn 7 The seco ef a jor ee of information in determining the reaction pathway comes from the rate ee. . From the rate measurement data an empirical rate equation can be constructed. For simple ec unimolecular, bimolecular and termolecular reactions follow first, second and third order kinetics, respectively. However, the kinetic study involves a large number of things under consideration such as the solvent effect, the identification of the effective reacting species and its concentration, etc. Nowadays the measurement of kinetic isotope effects helps us under- stand which bond breaks and forms in a rate-determining step and we shall discuss this in detail in this section. (a) Kinetic isotope effects (KIEs) Changes in reaction rate owing to the isotopic substitution, either on the substrate or on the solvent molecules, are known as kinetic isotope effects. KIE has been observed in the chromic acid oxidation of isopropyl alcohol to acetone. CH3CHOHCH3+ H2CrO, ————+ CH,COCHs+ H20 + H2CrO3 Let the rate of a reaction involving a substrate containing a light isotope of mass number X be k, and that involving the substrate with heavy isotope of mass number Y be ky. Then, if kz # ky, we say that there exists KIE. KIE is expressed as kz/hy. When isopropyl alcohol and ‘a-deuterated isopropyl alcohol are subjected to chromic acid oxidation, the KIE, ie. ku /kp is found to be 7. However, there are three kinds of KTE. i. Primary kinetic isotope effect (PKIE), ii. Secondary kinetic isotope effect (SKIE) and iii. Solvent isotope effect. ae when k,/ky > 1, the KIE is said to be normal and when ke/ky <1, we call it inverse i. Primary kinetic isotope effect (PKIE) ‘A PKIB is defined as the change observed in the rate of a reaction when the bond to the Substituted isotopic atom of the substrate is broken or formed in the rate-determining step. In the oxidation of isopropyl alcohol to acetone by chromic acid, the a C-H bond breaks in the R.D. step. So, the reaction shows a normal PKIE and it is 7. ky Me2CHOH + HCrO;+ H® —#_., Me,C=0 + H20 + H2CrO3 kp. Me,CDOH + HCrO;z + H® Me2C=0 + H20 + HDCrO3 PKIE, ic., ku/kp =7“ eeeFundamentals of Organic Reaction Mechanisiqusmmmamessesmmmmemmmmmmmassnas 55 that between the two sets of reactants (A— a in thei nt Gi the AG! ofthe reaction biween Ae tm AD +B) ht ound and B will be less than that of the reac- tion between A——D and B as shown in the figure given below (Fig. 11.10). So A—H bond breaking will occur faster than A—D. bond breaking, ic., ky > kp. PKIBs have also been observed in the reactions involving simple breaking or formation of one bond in- stead of atom transfer as shown in the exam- ple above. Retro Diels-Alder reaction is an example of such a reaction. 170°-200°C Retro Diels-Alder Diels-Alder Hi Here bond breaking and bond formation occur in a concerted step. PKIEs are essentially negligible for isotopes of mass number greater than 20 to 30, but they may be very high for isotopes of hydrogen and ky /kp ranges from 1 to 8 and even 9. The ‘maximum normal hydrogen-deuterium isotope effect at 0°C is 8.3. PKIE values for different isotopes are given in Table 11.3. ‘Table 11.3 Maximum normal values of PKIE.s at 25°C ha /kp hua/Iis Hydrogen kur /kr Ona kye/kig 1.02 rb hio/kia { ‘Sulp kao/kag 1.01 Carbon —kin/kig, 1.07 Chlorine agar 1.01 The PKIE values, specially ky /kp values, depend on two main factors : () It depends on temperature—It decreases with increasing temperature. The maximum norinal hy /kp at 25°C is 6.4 while that at 0°C is 8.3. The PKIE—temperature relation is given pa Rb ado fe eee (11.2) saliien = Free energy of activation of the substrate containing heavy isotope —free energy of oe activation of the substrate containing light isotope. ve bi 3) Oe Taira gas constant and T = Temperature in degree kelvin. 7 ‘values depend on the structure of the T.S. The maximum isotope effect is expected and symmetrical T.S. having the isotopic atom placed centrally between the two yrtant role in determining the reaction mechanism. If no PKIE is observed ‘we can conclude that the R.D. step does not involve the braking or making of _ Ahigh PKIE value indicates, on the other hand, that the particular bond breaksFundamentals of Organic Reaction Mechanis!, 553 H ‘OMe C80: cH=OM o a et O—~Me CHjCH=OMe H,0°+ CH;—C—H 8a H,0 + CHy—C2—8 spots, + OMe OMe MeOH H,0 slow i Con H® o—H oe we _H® H CHs—CH a CH;—CHt x CH;—CHt 30—Me ~H No—Me ‘No—Me WW” jo CHy—CH=0—H yh H MeOH The solvent isotope effect here (ky /kp) varies from 0.33—0.55. ‘The solvent isotope effect also plays an important role in the elucidation of the reaction mechanism. From the solvent isotope effect, the slowest step in the hydrolysis of acetals has been determined. H2O addition step is the R.D. step. CHjCH=0 ky/kp = 0.33-0.55 Very often a reaction intermediate is proposed to draw the reaction pathway of an organic reaction. Either the isolation of the intermediate or the detection of its presence may be a strong evidence for such a proposed mechanism. For example, the mechanism of the reaction between ethyl picrate and methoxide ion has been established by the isolation of Meisenheimer salt which is a complex intermediate in the reaction, Et 7 OMe Me NO) NO» NO. NO, NO2 NO) OMe OEt ° NO, : NO» Et 2 Va: Ethyl picrate Meisenheimer salt Methyl picrate The detection of reaction intermediates may be done by infrared, nuclear magnetic resonance, electron paramagnetic resonance or by other spectral studies. They may be detected also by trapping. The detection of nitronium ion (NO2) by Raman spectra is regarded as a strong evidence that the nitration of benzene involves NO2.Advanced General Organic ¢ If one gets a stereoisomer as a product of a reaction, the form of stereoisomer prog re niany information about the mechanistic pathway of the reaction. The formation of ,.* S-libromobutane from the reaction of ¢::s-2-butene and Bry indicates that the additio,, to a C=C double bond is ty ns; if it were cis, the product would have been a racemic ¢.. If the substrate of a particular reaction is not a stereoisomer then by performing reaction on a properly chosen stereoisomer, one may know its mechanism. Tn fact, much information about nucleophilic substitution, elimination, addition an ‘mont reactions have been obtained from their stereochemical study. Stereoselectivity a specificity have great importance in this connection (Sec. 9.22). See See, 11.7.2 ‘This helps us determine whether a rearrangement reaction is intermolecular or intra: Ror the discussion See See. 14.1. Problem 11.6. The most stable carbenium ion forms most readily.—Explain. Solution : The formation of carbenium ions from stable compounds is an endo’ tion. According to Hammond’s post! will be carbenium ion-like. The most nium ion, therefore, will have the most ‘This means its AG* will be the lowest ate. So the most stable carbenium ion w readily. (a) Non-classical carbenium ions; (>) Ambident nucleophiles; (c) Nucleophilicity; (a) Hard and soft nuclophiles and electrophiles; (c) Reactivity and orientation; (£) Concerted step reactions and stepwise reactions; (g) Microscopic reversibility principle; h) Reactivity-selectivity principle; (i) Neighbouring group participation and anchimeric effect. 1. Write notes on :Fundamentals of Organic Reaction Mechanism qumssmmsmmmmnnnenmeeean 5 2, Write down the products from the oy multi-centreed T.S.s : CH, = =O me Pec a » ae OGG Y% No cH, a six-centred T.S, (ii) Meg ee ‘ou? Ane 34H, MeN “GH—CH;—CH=CH, —> oN ie C =CHy t O--H a five-centred T.S. we> OL peg S<—~Scuo CHO a six-centred T.S. Di er & A ° t pace on GEN So ony “Seriy No a six-centred T.S. (iv) CHa 4H CHa H ae Wyn tag He) | NH HYBH) He-BHy a four-centred T.S. (vi) ea" CH=CH ’ Pres a ee a F F roNE singlet a three-centred T.S. 8. Classify the following reactions as : i, Substitution Elimination; iii. Addition; iv. Rearrangement. (a) CHCl; we : CCly + EtOH + Cl-. (b) casas —. cx,on (c) CH3COCl eNets (CH3CONs+ NaClEr Fundamentals of Organic Reaction Mechanism 6. Write down the stability order of the following sets : ° (i) CHsCH,, CHs=cH—En,, 0 3 pe 7 - (i) CH—CL, CHy —6— Gu, (iii) :CClz, -CHCI, :CH, (all in the singlet state) CHy NO, nae. oh Ch (v) t-Bu cation in water and in gas-phase 0 0 H 7. Write down the products : Gs (i) CHsCH— Br (ii) PhCH=CHPh (trans) + -CHy He #20 (iif) CHy=C=CH, ———. —*—. Zn® (iv) Pitas Gh ) om —0— Er a CH