Page 1 :
Chapter 3.., Rearrangement Reactions, Contents ..., , 3.1, , Introduction, , 3.2, , Types of Rearrangements, , 3.3, , Types of Reactive Intermediates involved in different Rearrangements, , 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, , Beckmann Rearrangement, Baeyer-Viliger Oxidation, Favorskii Rearrangement, Curtius Rearrangement, Lossen Rearrangement, Schmidt Rearrangement, , 3.10 Pinacol-Pinacolone Rearrangeme, 3.11 Electrocyclic Rearrangements, 3.11.1 The Claisen Rearrangement, 3.11.2 Cope Rearrangement, 3.11.3 Mc-Lafferty Rearrangement, Exercise, , 3.1 Introduction, A rearrangement reaction is, , skeleton of, , a, , molecule is, , a, , rearranged, , to, , organic reactions where the carbon, structural isomer of the original molecule., , class of, , broad, , give, , a, , the same, group from one position to another within, The rearrangement involves migration of, molecule is known as molecular rearrangement., or in some cases migration is, of atoms to an adjacent atom (L,2-shift),, an atom or, , The, , migration of, , an, , atom or, , group, , Over longer distances., , where,, M, , M, , B Migrationterminus, , AB, , 1.2-shift AA, , he atom from which, which, , A Migration origin, , migration, , B, , M Migrating group, , migration begins is, , qroup, , moves, , known as the, , migration origin and the, , is called migration terminus., , (3.1), , atom to

Page 2 :
T.Y.B.Sc. Organic Chemistry, , Rearrangement Reactions, , 3.2, , I (Sem. V), , In rearrangement reaction, migrating group shift with its lone pair of electrons clled as, nucleophilic (anionotropic) rearrangement and migrating group shift without electron, pair is called electrophilic (cationotropic) rearrangement. In the rearrangement, if the, migration of group is with one electron then it is called free radical rearrangement., The, , most, , common, , migrating, , atoms are carbon,, , hydrogen, , or, , heteroatom. The, , nucleophilic 1.2-shifts are more common in rearrangement reactions. The rearrangement, , reaction involves two possible modes of reaction as shown below., R, , R, , A-8, , and, , A, , -C, , R, , R, , R, , R, , A- C with A - B and A-C, , A-B and, , Intermolecular rearrangement, R, , R, , )A-B, , and, , R, , R, , A -C, , A- B and, , A-C, , Intramolecular rearrangement, type, , of, , rearrangements are called as intermolecular rearrangement, , in, , which the group, , Ris completely detached from group A and may end up on the B atom or C atom of, another molecule. In 'I type of rearrangement, R going from A to B in the same, molecule, , 3.2, , is called intramolecularrearrangement., , Types, There, , of, , are two, , Rearrangements, key rearrangement, , reactions:, , 1,2-rearrangements and pericyclic reactions, (i) 1,2-Rearrangements: In this type of reaction the, migrating group carries the, electron pair with it, the, migration terminus B must be an electron deficient atom with only, Six, , electrons, , Carbocation, , in, , its Outer shell. The first, , can, , carbocation from, , alkene, , be formed from, an, , step, , is the, , formation of, , a, , carbocation intermediate., , alcohol, , (the acid treatment of an alcohol to give, intermediate oxonium ion), alkyl halide, (reaction with AgNO3) and, , (electrophilic addition to C=C)., , R, A-B, , R, , H, , oH, , HH, , B, , H,O, , H, , -C-H, H, , H, , Carbocation intermediate

Page 3 :
T.Y.B.Sc. Organic Chemistry -I (Sem. V), , Rearrangement, , 3.3, , rearrangements are, Beckmann, Baeyer-Villiger,, Cutius, Pinacol, Wagner-Meerwein Rearrangement, Examples, , of these, , Lossen, Schmiat, , H, , HO, , H,O, , i) Pericyclic reaction, carbon bond, , making, , and, , A pericyclic reaction is a type of reaction with multiple carbon, , breaking, , cyclic, pericyclic, , wherein the transition state of the molecule has, , Eamples, geometry and the reaction progresses in a concerted, reactions are Claisen, Cope, Diels Alder and McLafferty rearrangements, R, Y, (1,3), fashion., , of, , a, , H, , (1,5), H, R, , 3.3 Types, 3.3, Types, , of, , (1,7), H, , Reactive, , Intermediates, , involved, , in, , Different, , Rearrangements, Pearangement reactions usually, , involve carbocation, carbanion,, , carbene, , and electron, , ceficient nitrogen and oxygen intermediates. Carbocation intermediates are most common, , ir termediates in rearrangement reactions., earrangements involving, , Carbocation Intermediate, , The skeletal rearrangement of carbocation which involves migration of B-alkyl. aryl or, G-bond, , is, , called, , Wagner-Meerwein, , rearrangement reactions, migration, , of, , rearrangement., an, , In, , most, , of the, , carbocation, , atom or group occurs due to the formation, , more stable carbocation from less stable carbocation., , of, , Neopentyl alcohol on treatment, , with HCi gives the rearranged product 2-chloro-2-methyl butane.

Page 7 :
T.Y.B.Sc. Organic Chemistry I (Sem., , 3.5, , V), , Rearrangement Reactions, , 3.7, , Baeyer Villiger Oxidation, , .The treatment of ketones with peroxy acids or with hydrogen peroxide, in the presence, , of acid catalysts, a formal insertion of oxygen followed by migration of alkyl or aryl group, can take place to yield a carboxylic ester. This reaction is called the Baeyer-Villiger, rearrangement., , H,0. H, or, O - R, R - C, , R, , oO,, R, , RR--OH, , ina first step, the carbonyl group is taking the proton from acid and protonated to form, , carbocation intermediate., In the second step, the peracid adds to the carbocation to form Criegee intermediate, n the third step, migration of alkyl or aryl takes place with the elimination of carboxylic, , Oo-H, , O-H, , R, , R, -R, , ~oH, , R, , The ease of migration of substituents R, Rz depends on their ability to stabilize a positive, cnerge in the transition state. For unsymmetrical ketones the approximate order of, , igration is RC > R,CH> Ar > RCH,> CH3.The CH3 group has a low migrating ability,, ara the migrating ability of aryl groups is decreased by electron-withdrawing and, , ncreased, , by, , electron-donating, , substituents., , The, , Baeyer-Villiger, , oxidation, , unsymmetrical ketones is regioselective., , Bu, , FC-COOH, , o-H, - 0-0-C-CH, Bu, , Bu, , 1, , -HH, , O, , +CFC, Bu, , of

Page 13 :
Rearrangement Reactions, , 3.13, , T.Y.B.Sc. Organic Chemistry I (Sem. V), , In the second step the isocyanate is hydrolyzed in the presence of H,O., In the final step, the respective amine and CO, are generated by abstraction of a proton, with a base and decarboxylation., OH, , R, , R, , =O=0, , R, , R-CO2, , H,O, , R-NH2, , CO2, , -CO2, , H,O, , OH, , B:, H, , R, , R, , N=Ö=0, , R, , -R-CO2, , R, , Examples of Lossen Rearrangement, CH3, , NaOH, -H%O, , ON, , NH2, ON, 4-Nitroaniline, , N-acetoxy-4-nitrobenzamide, , CH3, , N, , NH2, , KOH, , -HO, , H, , Furan-2-amine, , N-acetoxyfuran-2-carboxyamide, , 3.9 The Schmidt Rearrangement, An azide when reacts with a carbonyl derivative, usually a aldehyde, ketone, or carboxylic, , amide, with the expulsion of nitrogen is, known as Schmidt rearrangement. It is named after Karl Friedrich Schmidt, who first, , acid,, , under acidic conditions, , give, , an, , amine, , or, , reaction of benzophenone and hydrazoic acid., reported the synthesis of benzanilide from, The reaction is effective with carboxylic acids to give amines, and with ketones to give, amides., R, , H+H-N-NENN, R, , HNH, , HH-N-NEN, H,O, , HO, , R, , N-H, , R

Page 14 :
T.Y.B.Sc. Organic Chemistry I (Sem. V), , Rearrangement Reactions, , 3.14, , Mechanism:, Ihe reaction is, , closely, , that in this reactin, rearrangement except, with hydrazoic acid via t., of the carboxylic acid, he, , related to the Curtius, , produced by reaction, protonated carboxylic acid, in a process similar to a Fischer esterification. An alternatiue, , the acyt azide is, , tive,, , becomes more important when the, bn, involving the formation of an acylium ion,, takes place in concentrated acid (>90% sulfuric acid). (In the Curtius rearrangement, , reactin, , sodium azide and an acyl chloride are combined to quantitatively generate the acyl azida, , intermediate, and the, , rest, , of the reaction takes, , place under, , neutral, , conditions.), , This mechanism begins with the formation of an acylium ion 1 from the protonation of, , the carboxylic acid followed by the removal of water., , This acylium ion is now reacted with hydrazoic acid, leading to the formation of a, protonated azido ketone 2., , Now. the protonated azido ketone 2 and the R group undergo a rearrangement reaction,, resulting in the migration of the carbon-nitrogen bond and the removal of dinitrogen, , eading, , to, , the formation of, , a, , protonated isocyanate 3., , Now, a carbamate 4 is formed when water is introduced to attack the protonated, , isocyanate., e, , carbamate 4 is now deprotonated. The subsequent removal of CO2 yields the, , recuired amine., O, , ., , H, , oEN, , -HO, H, , H, , H, , -N2, -H, , R-NH2, , R, , H H, , 5, , do, , 4, , 3, H, , In the reaction mechanism for the, , Schmidt reaction of, the carbonyl grou., activated by protonation for nucleophilic addition by theketone,, azide, forming, azidonyn, 3, azidohydrir, which loses water, , in an, , elimination reaction, , to, , diazoiminium, , groups migrates from carbon to nitrogen with, intermediate 6, as in the Beckmann, , protonated, In, , an, , alkyi, , ary, , loss of nitrogen to give a n, to, rearrangement., Attack by water conv c acid, arid, imidic acid 7, which, undergoes loss of proton to arrive at the, , imia, , tautomer of the final amide 8., ., , 5. One of the, , alternative mechanism,, , the, , migration occurs, , at 9,, , ter protonation o, , directly after protonded, the, protonat, Baeyer-Villiger reaction to give, give, , intermediate 3, in a manner Similar to, amide 10. Loss of a proton again furnishes the amide, , 8, , T.

Page 15 :
T.Y.B.Sc. Organic Chemistry-I (Sem. V), , 3.15, , Rearrangement Reactions, , It has been proposed that the dehydration to 3 to give 5 (and, hence, the Beckmann, pathway) is favored by nonaqueous acids like conc. H,SOa, while aqueous acids like conc., , HCI favor, , migration from, , 9, , (the Baeyer-Villiger pathway)., These possibilities have been used to account for the fact that, for certain substrates like, a-tetralone. the group that migrates can sometimes change, depending on the, conditions used, to deliver either of the two possible amides., H, , N, , HO N, , N, , RNH, , B-V, pathway HO, , RR, , 2, , 9, , 10, , I, N, R - N g eckmann, , H2NO, , pathway R, 6, , 5, , RNH, , N, , R', , R, , 4, , Tautomerize, , R-N=R, , HO, , -H, , R-N, 7, , OH, , R-N, OH, , Examples of Schmidt Rearrangement:, , ON, , O, , ON, , N, , O, , -OH, , HSO4. 80-100°C, 15 min., -OH, 63%, , N, , MeAICl2, , CHCl2, , 96%, , 3.10 The Pinacol Rearrangement, When vicinal diol is treated with a catalytic amount of acid, it can rearrange to give an, aldehyde or ketone by migration of an alkyl or aryl group which is called as Pinacol, Rearrangement. The pinacol-pinacolone rearrangement reaction or 1,2- migration can be, viewed as a special case of the Wagner-Meerwein rearrangement.

Page 17 :
T.Y.B.Sc. Organic Chemistry - I (Sem. V), , 3.17, , Rearrangement Reactions, , second step, 1,2-shift of a R group to the more stable (lIl°) carbocation takes, place, give a more stable hydroxyl carbocation intermediate. The reaction is intramolecular;, , In the, to, , migrating, , group R is never completely released from the substrate. The driving force, is the formation of the more stable rearranged carbocation, which is stabilized, by the, hydroxy group. In the third step, loss of a proton yields the carbonyl compound., , the, , 1,2 CH, , CH O, , HOH, , H, , shift, , HC-, , HC-, , CH, , -H, , H,C-C-, , CH3, , T Carbocation, , -, , H, , CH3, , Carbocation stabilised by, , CH, , hydroxyl group, , HC-C-, , CH, Reaction with an unsymmetrical diol as starting material may give rise to formation of a, mixture of products. Mixtures are product formed, may depend on the reaction, conditions which group preferentially migrates as well as on the nature of the substrate., , The order of migration is R,C > R2CH > RCH2 > CH3 > H., , CsHs CH, , HC, , -¢-CH, OH OH, , -H,O, , 1,2-CH3, shift, , CoH CH, , H,--CH, , CH CH, , H,-¢-, , Cot, , CEHO, , More stable,, stabilized by two, Ph groups, , -c-CH, CoH CH, CH.COOH, , H,C-, , a trace of H2SO4, , -CH, , -H0, , CeHs CH3, , 1,2-Ph, , CH3, , shift, , -H, , HC-C--CH, , :OH, , OHOH2, , CeHs, CH3, , Less stable, , The action of cold, conc. H,SO on A produces mainly the ketone B (-CH3 migration), while treatment of A with acetic acid containing a trace of H,SO gives mostly C (pheny, , hydrogen, aldehydes can be produced as well as ketones., Generally, aldehyde formation is favored by the use of mild conditions (lower, migration). If, , one, , R is, , temperatures, weaker acids)., , Ph, Ph-C, OH, , Ph, , Ph, , Ph, , -CH, OH, , Ph-CPh, , Major, , C-CH, , Ph-C-C-Ph, , CH, Minor

Page 20 :
T.Y.B.Sc. Organic Chemistry I (Sem. V), n, , the ortho, , migration,, , the, , Rearrangement Reacti, , 3.20, , allylic, , group, , is, para-Claisen rearrangement there, as it was in the oniginal ether, , allylic shift. Whereas in ., is f, allylic shift. The alylic group toun, , always undergoes, , never, , an, , an, , exactly, , Me, , Me, , Me, , Me, , Me, , Me, , O, , OH, Me, , Me, , ste, , Me, , 13..31, 3, , 3. 3, , 3.11.2 The Cope Rearrangement, T h e Cope, , Rearangement, , regioisomeric, , is, , 15-diene. The main, , recioisomer., , leading to, more stab, product is the thermodynamically, , the thermal isomerization of, , 1,5-diene, , a, , R, , R-, , The Oxy-Cope has a hydroxyl substituent on an sp°-hybridized carbon of the starting, Somer., , HO, The driving force for the neutral or anionic Oxy-Cope Rearrangement is that the prodiu3, is an enol or enolate (resp.), which can tautomerize to the corresponding carbon,, , compound. This product will not equilibrate back to the other regioisomer. The Oxy-Cope, Rearrangement proceeds at a much faster rate when the starting alcohol is deprotonatec, e.g. with KH. The reaction is then up to 10* times faster, and may be conducted at roo, emperature. Aqueous work up then gives the carbonyl compound., , O, , HO, , HO, , O, , HO, Mechanism:, , -, , R, , R, , R, , R, , N

Page 21 :
T.Y.B.Sc. Organic Chemistry I (Sem. V), , 3.21, , Rearrangement Reactions, , Two transition states are possible, and the outcome of the reaction can be predicted on, the basis of the most favorable overlap of the orbitals of the double bond, as influenced by, stereoelectronic factors:, OH, , OH, , -, , -H, , 2, , H, , Examples of Cope and Oxy-Cope Rearrangement:, Heat, , A, , 3.11.3 The McLafferty Rearrangement, The McLafferty-Rearrangement is observed in compounds in which at least one, abstractable gamma (y) hydrogen is present with respect to a pi (T) bond. When such, compounds are ionized as molecular ions, in mass spectrometer, usually by the Electron, lonization (ED method. The resultant molecular ion undergoes a special type of, gamma (y) position transfers to the carbonyl functional, group followed by the hemolytic cleavage of the Ca-Cp sigma bond. This rearrangement, , rearrangement. The hydrogen, , Tinally, , at, , results in the formation of, , an, , olefin without any, , charge and, , an, , enol radical cation, , as products, , Ihis rearrangement is widely observed in Aldehydes, Ketones, Carboxylic acids, Esters,, Amides, Imines, Cyanides, Alkenes, and Alkynes. The McLafferty Rearrangement is helpful, in the identification and characterization of various organic molecules., , Mechanism:, R-, , Z,Y = C, N, O, , H

Page 22 :
(Sem., , Rearrangement Reactio-, , 3.22, , V, , T.Y.B.Sc. Organic Chemistry, , I, , Examples of McLafferty, , Rearrangement, , OH, , OH, , OH, , CH2, , R, , R, , Exercisse, (A) State True or False Questions, in rearrangement reaction,, , (1), , migrating, , its lone, group shift with, , called as electrophilic rearrangement., The skeletal rearrangement of carbocation which involves, , pair, , of electror, , migration of B-alkyl,, , ar, , or d-bond is called Wagner-Meerwein rearrangement., Rearrangement involving carbanion is Favorskii rearrangement., Vicinal diol on treatment with a catalytic amount of acid, rearrange to give, aldehyde or ketone is called as Baeyer Villiger rearrangement., 5) Allylic aryl ethers, when heated, rearrange to ortho-allylphenols, this reaction, called the Cope rearrangement., 6) The McLafferty-rearrangement is observed in compounds in which at least or, , stractable gamma (7) hydrogen is present with respect to a pi (7) bond., (7), , Allylic ethers of enols (allylic vinylic ethers) also undergo the Claisen rearrangemer, The Cope rearrangement is the thermal, isomerization of a 1,5-diene., , 8), 9) In Pinacol rearrangement, the order of migration is R,C < RCH < RCH2 < CH3 < H, (10) In Lossen rearrangement, azide reacts with a, carbonyl derivative, usually, aldehyde, ketone, or carboxylic acid, under acidic conditions to, an amine, , give, , amide, , (11) When B-halo ketones are, treated with base, in the, presence of nucleophile, reaction is called, Quasi-Favorskii, (12) In pericyclic, rearrangement the net result is one pi bond being, converted into, bond, Sigma, or vice, versa., , rearrangement, , (13) In, , Baeyer Villiger rearrangement, for, unsymmetrical ketones, ofmigration is R3C >R,CH> Ar, RCH,>, CH., (14) In Beckmann, >, , rearrangement,, , they form nitrile., 1. False, , 2.True, , 8. True, , 9. False 10., , aldoximes often, , 3.True, False, , are more, , the, , approximate ord, , reactive than, , ketox1me, , ANSWERS, 4. False, 11. False, , 5., , False, , 12. True, , 6. True 7 . Tru, 13. True, , 1 4 Fals