gap NGEMENTS Q@ 399 CH, AICIYRCI Tena =A, CH, CH, a janov or Tiffeneu-Demjanov Rearrangement , 2 _~ ‘When a 1.2-migration is initiated through formation of carbocation by diazotisation of a primary amine, reaion is termed a2 Demjanov rearrangement, The reaction has found particular application for the We jon of acyclic rings by one carbon atom, eleaikylmethylamine undergoes ring expansion by one carbon where as eycloalkylamine undergoes gconration by one carbon in this reaction. For example, when cyclobutylmethylamine (1) is treated with rsa it gives both cyclobutylcarbinol (2) and eyclopentanol (3) besides methylenecyclobutane (4). The featon of these products can be readily rationalised by considering all the three typical properties of fibeaion, viz., addition of nucleophiles, elimination of a proton and rearrangements to a more stable aatecation, (Scheme-1). 44 Dem} i-CH—CHy—NHa, yo, CHa—-CH—CHy— \ | =~ | CH CH2—CH2 CH;—CH—CH,0H CH2—C=GH, I A} | CHy—CHy CHy—CHy @ CH)—CH, 10 Cliy-Cih ah "\ch—> 7 NCH a CH —CH, cc Ging expansion by one carbon atom)” CHy— CH CHy—cH/ ° yeody i 7 ‘Scheme-1 7 . tana tbutylamine (5) yields both cyclobutanol (6) and cyclopropyl carbinol (7). The mechanism of these “ware as follows (Scheme-2): zB @ CH2—CH—NH “no, “CH —CH-N=N b I ae | H—CH, bap 6) CH e ® i es i Seu2u, 1,2-Shift oH ez 2 cH, cH, ~ ® HOH [et Hay CHy—CH—OH CH—CH)—OH | bu, 2 babu, = o © ‘Scheme-2- © ‘sa non-classical carbocation which is very stable carbocatig e the C—C bonds in cyclopropany 400 Cyclopropylmethy! carbocation i carbocation is stablished by C—C sigma electron delocalisation sinc appreciable p character. ‘An interesting situation has been observed in deamination of cyclopropylmethylamine (9). This cyclopropyl carbinol (7), cyclobutanol and allyl alcohol (9) (Scheme-3). yh Cla CHy—CH—OH | Scu—cH;—on +] | + CHy=CH—CH; CH vo, CHa CHa as 2—CH20H o o © Formation of these products takes place by the formation of stable non-classical carbocation, i CH HNO |. ScH—CH)>—NH; —— CH’ cyclopropyl methyl carbocation CH HNO; @ LScu—crip nips = by7’ jg—NH2: byte N CHa ou, 2 b er-cri01 en | ects Ho on, 48% 1,2-shift CHy=CH—CH,—cH,0H HOH cH, —cH—cH, En, 4 om ea) Scheme-3 Similarly, cyclopentylmethylamine, eyeloy ’ ._ eyclohexylmethylami t cyclooetyimetiylamine yield respectively cyclohexanol, eycobe vlamine, | cycloheptylmethylamine and wit ober produ, Planol, cyclooctanol and cyclononanol, al¥4¥ fe have already seen thi ino. ly seen that B-ami e-seohos undergo 1,2-nucleophilic rearrangem tient wil | chet lic jent on treatin referred to as the semipinacol rearrangement (Schem™@ pea RANGEMENTS. 401 iromethane OF diazomethane. This reaction is applicable to those cyclic ketones which contain three to seven ans in the ring of the substrate. Homologation of cyclic ketone with nitromethane takes place as follows (Scheme-5). 8 9 OH, ,CH,—NO, HO. ,CH,—NH, HO. ,CH,—N=SN city —NOJNGOE Hy Raney Ni HNO. SL SNOUNOE afew \ ® o uLoy cH, G+ CCycloheptanone ‘Scheme-5 _ Homologation of cyclic ketone with diazomethane takes place as follows (Scheme-6): ‘Scheme-6 The yields of this process are frequently’ lower than those obtained by the diazotisation of f-amino alcohols, as epoxides are formed 'as the by product: Odiufen Os CH, i, z20 Epoxide as by product \ Whilst diazomethane is commonly the reagent used for this conversion due to the ease of its preparation, higher homologues may also be used in the Tiffeneu-Demyanov rearrangement. Gl cl jet ch cu-of—fN pp. 0 MeOH, E40 Ph’ CH, 43 18 Dienone-Phenol Rearrangement : ally This rearrangement is given by those ‘compounds which have 2,5-cyclohexadienone nucleus having two FOXPS at position-4, ai io atment with acid, 4,4-dialkyleyclohexa-2,5-dienones (1) rearrange to phenols 4n alkyl group to an adjacent ring position. fi ne ee ele (8) throughanc a ee cs wt Benzilic Acid Rearrangements eo axetones undergo & rearrangement when treated wi son, pivi Dik with hydroxyl ion, giving a-hydroxy acids. The best example is the conversion of benzil (1) into anion of benzilic acid (2) which on acidificati jon converts Neale 20 G)- 433 t a e BP. a OH cetis eC —Cats cei gt, cate eC Cells Cais 8 2 @ she ceiving fore for the reaction is the formation of carboxylate ion. ‘Tus rearrangement also takes place in the presence of alkoxide ion which directly converts a-diketones sap exer of ochydrony acid (4) 090 OH il OCH 0° I 1s CCCs ——> aa (i) H oe Cals a In 1928 Ingold proposed the mechanism of this rearrangement shown in Scheme-I which is today sepored by experimental evidence. ° ' ri CH-C-¢— 0-H Sat, cae e— OH CH CH OH = OHO e GH-o-e—0 CAs ‘Scheme-1 This reaction is second-order each in benzil and in base. e Rate « [OH] [Bemzil] Rob 8 < im and Urey carried out the rearrangement with H'SO and found that the label was incorporates = reacted banzil (5) at a faster rate than the rate of rearrangement. Thus the first SteP must be rapi Tete Hence first step is not the rate determining steP- 9° 08 qk OH to I Il ce? = Colts e Cols xe 9 is no I CgHs—C—C—CeHs, EE Ces {j dis 2434 OFSANE Sn, & When reaction is carried out in the presence of 6p, it has been found that there is effect. This confirmed that third step is also not the rate determining step. By elimi migration, step-2, as the rate determining process. An intersing aspect of this rearrangement is that phenyl group with the lower electron 0 deuterium ig, nation, that le di usually migrates. For example in (6), the substituted phenyl migrates 80 per cent of the time it Gann but only 31 per cent of the time if G is p-methoxy (Fig. 1). Shag, Oo Oo Ii C—C—CH, 6 9 0 Ii jou C—C—CH, ——— > CHL (i) HOM Fig. 1 } In other words, we can say that in this rearrangement if the aryl group of one of the carbonyl carbons. has +R group at ortho or para position and the aryl group of the other carbonyl carbon has no +R group a ortho or para position, then migrating group is alwlays which has no +R group at ortho or para position Figs 2 and 3). ii al ww cx{O)- —C—CH, o1-O)-e--O) ae Saar J Ll bx w\ 1) +R group of no +R group +R group at ring has + R group i SS pposition hence this group will migrate p-position but R group is not at ortho or para postion ws te i YS hence this group will mgr ES : ae Fig.2 Fig. 3 4 The reaction for this migratory aptitude can be explained as follows: migrating group always beloms oy Qe 8 s othe carbonyl carbon on which OH attacks. Nucleophile, OH, gives nucelophilic addition on the castor! carbon which is more electron deficient in nature, i.e., group attached to it should be electron withdraw Less electron deficient due to more el ficient deficient ufo. ore electron deficient than earbon I, Heed CHO group __ OH will atack on carbon-2 and not on carbon-1 Fig..4 Another interesting aspect of this rearrangement is that the use of alkoxides can give rise to complicated mixture of products, mostly from reactions unrelated to the bwnzilic change. Thus, with alkali metal hydroxides, reduction to bwnzoin is prominent. It is finished from this that the hydrogen atom of the hydroxy! ion must play an essential part in the hydroxide promoted rearrangement (Scheme-2),‘Scheme-2 mited to diary! ketones. The reaction rearrangement is by no means li ‘This type of m aromatic-aliphatic Ketones (Fig. 5). Thc 8 () OH Cots —CH: Lf cgi; OO Gi) HO? Fig. 5 Some Purely aliphatic ks | : Fig. 6 “Cyclic 1, 2-diketones gives D-hydroxyfluorene-9-carboxylic acid (Fig. 7)- ccan undergo the benzilic change with ring contracti 435 Ph I Ph— ao c=o oo— n is observed with OH COOH duns CgHs—CHr tones also give this rearrangement (Fig. 6). OH ° oon OK, ooc—cHyl—COOH CH,—COOH citric acid ion, e.g., phenanthraquinone 2 CO = (i) Hon? ¥. HO COOH Fig. 7 Similary, the acyclic cyclohexane-1, 2-dione gives 1-hydroxycyclopenté e (i) OH “wonon® Ch Fig. 8 However, th os scope of the rection in the aliphatic series is limited by competing reactions, 8: ane carboxylic acid (Fig. 8). OH Xeon for example: ea Tt i q i Hy +CHs—C Loy, meet oy NL on Lh CH Dimethylglyoxat HAC ° Hy Tairamolecular Claisen reaction CH,436 ORG Ao om Gt-Ketoaldehydes also give the rearrangement, ¢g., phenylglyoxal gives 2-pheny.2 4 + 2-hy dro Fig. 9). "ein, 1 OH Cels—«—cOoH H tf <8 CgHs—C—c—H-O8 (i) HOM? Fig. 9 The mechanism of the reaction in this case coincides with that assigned to the intram reaction. 1, 2-Diketones also give rearrangement with carbon nucleophiles. Benzil gives t 2-Dike : etary ce treated with Grignard reagent (Scheme-3). a oa So ad oo O—Mgx O° ir Gi ue io, OE ae : A — Ana C—Ar RCE OME TS pe fl R—MgX | i cee ‘Scheme-3 4.3.5. The Favorskii Rearrangement a G-Haloketones react with base to give enolate which rearrange to acids or ester via cyclopropane intermediate. The rearrangement is known as Favorskii rearrangement. The most commonly used base a alkoxide ions, which lead to esters as the reaction products (Equation-1). When hydroxides are used, the produ! of the rearrangement are carboxylic acids’ (Equation-2). oleculat Ceti, Ar 9 ° I @ CHO ) R—C—CH—CI 5 R—-CHCOOC>Hs va (ii) H,0/n® ® Il @on tC) Hs —CHy—C—CH,—Br- 9“ ___, cts —CH—CH—COOH : (ii) HOHH® ‘Two isomeric a-chloroketones (1) and (2) give exactly the same product on treatment with methoxise- This result suggests that both reactions take place through the same reaction intermediate. is 9 a II 5 C6H5~CHy—Ctz—CoocH; «catty -der_L_cHs (i) HOH @ 9 e @cH,6 cate tcc Similarly, if the ketone is unsymmetrical, two products aré obtained (Equation 3): CH; ies @ CH50°/C,H50H Z (CH3—CH—C—CH7—C ans a now? CH; CH; CH3 CHts—GH—CH~COOC Hs + citz-f-cootst A) ‘The mechanism of the reaction is shown in scheme-I. The reaction is initiated by the formation of 4% enolate ion which undergoes intramolecular (in some ‘cases intramolecular) nucleophilic substitution reaction437 i exnRANGEMENT opane intermediate thus results due to 1. tion of cyclopt ctive, presumably because of the large strain nes are very reat ered ring. they are resistant Jopropane intermediate. Formal ‘and X) reaction. Cyclopropano’ brid carbon in a three memb e very rective, ip form a 076 elimination (A cited with $7” by! h cyclopropanones ar‘ to enolisation because that would place Althoug! two sp? carbon atoms in the three membered ring (Equation-4). "Thus cyclopropanones give nucleophil addition at carbonyl carbon rather than the enolisatiion reaction. 1 to conversion of sp” hybrid carbon into sp? hybrid carbon. elephilic addition relieves some of the strain du ‘anion that is proton the rng then opens to give ® transient cart isthe nucleophilic migration ot an alkyl group from the carbonyl carbon to OR arrangement is that an alkyl gr ated by the solvent. The net effect of this process the o-carbon with the loss of halide. consequence of the Favorskii re oup is transrerred from one ‘The overall side of carbonyl group (0 the other (Scheme-1). ° i} ROCHE AE ix le {[Bee 8 9 I <> RCHS CHC é De 5 coor" coor” — oS breaking of ile. Waar | a BRR pond be R—CH—CH—R!'——_ R—CH—CH;-R’ breaking of ‘bond ‘a’ gitecd R—CH— CH: ira — becont 1 OR” E> RCH cOoR” R i 4, (Scheme-1)438 ORGANIe sn & ° ‘ 8 i sl ZN Su uN = R—cH—cH—R ty C—CH—R <> rc Nye Large angle strain due to 3 4 three membered ring structure ‘ ‘ Three membered ting structure and one carbon is present in in which two carbons are in sp? hybrid state ; hybrid state, Hence this will have high degree of angle strain. Due to this reason, this is not formed, In Scheme-1 cyclopropanone on ring opening gives transient carbanion. The carbanion in rearrangemint is not actually formed as a free species, three must be considerable negative charge atte cae atom as the membered ring opens. Because of the cyclopropanone mechanism, the structure of the product cannot be predicted direct fry the structure of the reacting haloketone. Instead, the identity of the product is governed by the direction of ty ring opening of the cyclopropanone ring. Direction of the ring opening of the cyclopropanone is gover by the stability of transient carbanion. Product formation takes place by the formation of the most stable carbanin in the ring opening step of the reaction. For this reason phenyl substituent favours breaking of the bond substituted carbon (which gives benzyl carbanion) but an alkyl group directs the cleavage to the less substiued carbon (Scheme-2). 0 &cit, a 9° " I © Cgi—CH,— C— CH,— Br Dom coocH, , ow Agel eet yy C,Hj— CH; — CH,— COOCH, <— CHs— CH CH, R—-CH- CH cH” \o/ \ of) | 4 poo Cpften gone Roc CHER! <— welll aS Ro <— n—cH—at—Sc I oH 1 oH OH COocH, R-cH— ; ccc ‘OH ‘Scheme ae442 4 ORGANIC Se Haloketones containing no hydrogen at o’ ii : i M7 @'-carbon also undergo Favorskii rear i . so fompounds cannot enolise and hence cannot form cyclopropanone intermediate, no eg emmbounds the Favorskii rearrangement may, in fac tllee semi benzilic mech” Pe rearrangement is reffreed to a neti, is quasi-Favorskii rearrangement or semi-benzilic real Of the rearrangement is carboxylic acid or ester (Scheme-10). nrangement Pog Q a Se EE ua ofl no hydrogen on Scheme-10 Qucsi-Favorskii rearrangement is also given by o-halocyclobutanone (Scheme-1 1). This cannot rear: via cyclopropanone intermediate, presumbaly because of large strain associated with bicyclic compoun undergoes a base catslysed pinacol type rearrangement (ie, semibenzilic rearrangement (Scheme-11)} Br 0 oe Rg Se a) 2, | wy Sas Scheme-11 In quasi-Favorskii rearrangement there is inversiin at the migration terminus (Equation-5). Br COOH a, C=O NaOH/Xylone Ph aS @-Halosuiphones undergo similar rearrangement known as Ramberg-Backlund rearrangement. eA o y l (Bx, ~ ee: (2 Pann : * x 0 x 0 \ q se lood R—CH=CH—R’+S0, <~ R—c} CHR . Thine dioxide ‘Scheme-12 31 Ro GHP’ x 0NT } eee 443 ned by deprotonation gives unstable thirane dloxide which, decom | i ‘of SO2 (Seheme 12) ss ‘ proses with the | nein ¢angement is useful for preparing alkenes in the smll ring. This rearrangement i | reparation certain types of stained alkenes (Equation 6, 7 and 8). anes weet itt H! so. Nie \ ¢ Het oe 6 | curso, 80: H—Cl I | od — OO : a be ; 1 ee BuOK/THE/S vn f8) $0 oH 50; CH; I a saethe Neber Rearrangement <9 ‘This rearrangement is given by ketoxime to ofthe rearrangement may be alkoxides of pyridine. R—CHy—C—R’ \—OTs uenesulphonates (1) in the presence of a base. The base wo R = arly of alkyl or hydrogen R’ = alkyl or aryl but not hydrogen | | | Product of the rearrangement is d-amino ketones (Equation-1). This rearrangement is one of the ‘Aldoxime toluenesulphonates do not est important methods for the proparation -amino ketones. Mdergo this rearrangement. e 0 Ree R—CH-C-R’ s + NOT NH) O. The ae f bent ne involves initial deprotonation of the migration origin. For this reason a-carbon of BUD. The 6 ne: have at least one acidic hydrogen. The reaction will be more efficient if R is a phenyl | "form an interne Obtained by deprotonatiion undergoes internal desplacement of the leaving group intermediate azirine. Azirine on hydrolysis gives the product (Scheme-1).4 Sr i N, ons, etl 7 N Roc cor: Sy Bek eR ge ei N—OTs @ pills o ° wf ARQ ss x mopictan <— mai ee et a, i Na, on ie @ gf Scheme-1 Neber rearrangement shows no dependence upon the stereochemistry Of the oxime sulphonate Bo syn and an anti ketoxime give the same product (Scheme-2). ; No, No, 5 OGKio I ’ O,N: ‘CH;— C—CH, — NOs CH—C—CH, I Gi Hom I 4 N-OTs NH, 4 o o OCH (i #,9 NO, I N-OTs Scheme-2 © In this rearrangement it is the substituent processing the most acidic a-hydrogen whch migrates on trogen atom giving azirine. 4 i i 7 T gthee dambered ring intermediate azirine (8) has been isolated and its structure verified by wen reaction. This experimental result confirms that product formation takes place by the formation oe 2 intermediate. Azirine (8) on hydrolysis gives the same product (7) which is obtained from the ketoxime Ly ester [(5 or 6) (Scheme-3)]. wolated ftom the reacton mixture sam. er NO; NO; i oOo Rae, om Ofgi— xn, o a ‘Scheme-3 ieHE): et — {uncertain that conversion of substrate into azirine is inter- ws sll Op been suggested that the ‘formatiion of azirine might pr Ith ¢ group to form a nitrene intermediate which then converts a 445 oF intramolecular replacement ‘oceed by stepwise loss of the into azirine (Scheme-4), S$ XE Ni ple ee ae tiene aes ion 5 perslopto Scheme-4 lar rearrangement is given by N, N-dichloroamines (10) (Scheme-5). A simi ¢ ° NC " 8 — CH, —C5- R* R—CH,—C—R’ RECHCHTR’ Gyn,0. | RCH: — Pp GH fick N—cl N. N a’ ‘a tY Na | an ° N I ° Ma R+cH—C—R’ <0 Ree, I azirine NH, Scheme-5aaa ORGANIC gy Stevens rearrangement is also given by sulphonium ion. In thi i phonium ion. In this case rearrange by the formation of sulpher ylide (Scheme-3). semen Poe q fe} @ Base I é CoHs—C—CH2—S—CHy—C ol. — 8. Hs z—S—CHy—Col 5 C,H Co ae CH-C,H, Hy Sulphur ylide | | CH, 9 3 \ @ CoHs— ft Soi See eaetir meeps CH2—C6Hs CH; Scheme-3 4.4.2 Sommelet-Hauser Rearrangement » This rearrangement is given by quaternary ammonium halids in which one of the substituents shou benzyl (1) or benzhydryl (2) and remaining substituents may be methyl or alkyl or both (3). @ 2 o . C¢Hs—CH—N——cH Cets—EH-NCCHDs Colts —CHy—N—CH)—R cay ‘CH3 cH H3€ CH a) Q) 3) @ oN with Benzyl trimethyl ammonium bromide (5) undergoes Sommelet rearrangement when treated Wi sodamide in liquid ammonial (Equation-1). i cH, CH-N. a cH, \, NaNHINHD/A cai, cH,— 8 es MO Cl CH, © | yca, ‘CH, Sb o 0 lar Crossover experiment showed that the rearrangement is intramolecular in nature. Intramolecu Te of the rearrangement has been confirmed by isotropic labelling experiments. Whe (7) and (8) are together, no radioactivity at all could be found in the product (10). t CH; tye case, REcH, + ca-kCon, cH, o Nou, cs Lo Oe spain 4 ee 4 e 2 ao) ‘cH, ay \GEMENT. | sos 449 se reaction mechanism involves initial deprotonation of the benzylic hydrogen which gives nitrogen ye THs nitrogen ylide is in equilibrium witha second nitrogen lide (12). Ylide (12) i formed in small vide (10 its stability. This ylide (12) is highly reactive species. Ylide (12) undergoes 2, 3-sigmatropic mnerate the product after reprotonation (Scheme-1). ek NaNH/NH3(1) oe oR CoHs—CH2— NEE, Cols CH ie be I CHR ain I cH, 1 J sR Hay VR R DS iin OF ne Scr by 3 Gi? my R oN ‘wopic rearrange R ot j 2) R’ cycle TS § (3) q z 5 g * CH; ee Ys | wine R | Od Re | ‘Scheme-1 | the initial rearranged product of the Sommet rearrangement is exomethylene derivative (14) this onetiylene derivative (14) readily converts into the product by the loss of profon. However, the ‘xonetylene derivative can be isolated if benzene ring of benzyl group does not have hydrogen. In fact, this iermadite has been isolated from the reaction mixture (Equation-2). CH; @ CH, aif pm b cuts hs LQ He ‘CH; HC ‘CHy—-NC Foy 09) an Cs ‘CH, Tamas ation of exomethylene derivative (17) can only be explained if one ean assume that ylide (12) is in the reaction mixture. "ning magia is carried out in DO then it has been found that reaction mixture contains the ucts: CH, CH: Cai, 3B, oe fis { ro Hy nO, cetigcH NK + ph i ‘CH Ge CHO. 450 ORGANIC STH E4 CHD CHD a CH, + cH Ov & CHN. ‘CHD—N en cH, eo Noy Isolation of (18) and (20) and These rearrangement have fot reaction is a tertiary amine, The Sommelet process repeated if ther (21) confirms the formatiion of ylide (11) as well as (12) und important applications in organic synthesis because Product ot Product tertiary amine may be converted into its quaternary salt and the € is a free ortho position available (Scheme-2). ° ,CH7—NMe, ‘ian CH, oan CH, HC Or aN a natn, fect CH, Me, 'CH—-NMe, Scheme-2 The main drawback of Sommelet rearrangement is that it also gives Stevens rearrangement in the presence of base (Scheme-3). R 7H, ch S—cu, CH, sSN—CH.—C)I is C,H ea Si CL hs Yn = (C),0 Bae 2 fmm CH, ,CHs apt OC lm Oo cH, Hs Finn bu, New, Later on Hauser found that when rearrangement is carried out in the presence Of CgHsLi, sodium alkoxide oF potassium alkoxide then quaternary ammonium halides give Steven rearrangement product as well 2 Sommelet rearrangement product. On the other hand, Sommelet type of rearrengement product can be obtained essentially and exelutively with the use of sodium or potassium amide in liquid ammonia (Scheme-3). @ .CH;—-NMe, NaNHYNHS(, a451 cen CHE Hs 7 ca Re ‘NaNH/NH3(D, ae _NaNHANHSO Or be Ol BN ‘CH. cH; Cs by eg, CH—NMe, CHy— CH 2 ‘NaNH,/NH3(). a sare ee eas ‘CH-N ‘CH, x NaNH/NH,(0). Ol CH; ‘Scheme-3 CH; 443 The Wittig Rearrangement ‘The base catalysed rearrangement of an ether to an al rearrangement (Equation-1). cohol via a 1, 2-shift is known as Wittig R R : Hc-o-w OS — H—C—OH a H qouemon .d sodium or potassium amide. In this rearrangement Bases used in this rearrangement are alkyllithium an ‘pon. There is no restriction upon the nature of the nrigation origing is oxygen and migration terminus is car cre abstvents of the ether as long as there is at least one acidic hydrogen present 01 to the oxyseh In eae ern oid R’ of the substrate may be alkyl, aryl, viny, 9flurencyl and 2, 4-cycohexadienyl. In tot ofthe cases migrating group R’ of the rearrangement may be alkyl (methyl and ethyl), alkyl benzyl, substituted benzyl and phenyl (Scheme-2). CH; © CoPsLilbs | Hls—CHy—O—CH3 OCHS cris CHOW -@ iy Hom® CHaCols @CeHsLifEQO CHls—CHy—O—CHy—CHs >= > Cs —CH—OH --G) Gy Hon® ca, @NaNH, eo i Qj ts C—CH_0 CH Cg Hts —_> > Cols —C_C OH oe) i Hom O Cols a Hf O—cH;-cH=CH, Aa Ci cb.a nseENTS e 419 Or NH,OH " 4 | R—C— 3 a H,O/0H RCOOME“cyi,oN NHOH | —“> R-N=C=0 ——S R—NHy 6 onversion of aromatic acids to amines is made possible by er, one-stage © : okt Pe le by an acid catalysed i rane Te comesponing Nyro acids are generated wher the carboxylic acid ae heated of the romethane i polyphosphoric acid and rearrange in situ to the protonated amines (6). it with 7 pat al Nuow | — Arse bx eee — Ar ACOH HgPODyA ae ‘Ar—NH2 O cular and its mechanism is identical to Curtius rearrangement. acids which are used to prepare the rearrangement ly than the Curtius or Schimdt rearrangements. : Lossen rearrangement is intramoles ' ree “he relative difficulty in obtaining hydroxamic that this method is used less frequent! precursors means \ freq or atemotecular mechanism of the reaction is ven in Scheme-1. The Base-catalyed mechanism 0 (where G=H, COR, COA") ‘The Acid-catalysed mechanism : ° a | l Iu a is aX 8—G > RNS C=O +G0H rR’ \wH—-G—G SE RCTS —N=c= Ne | H Scheme-t 4.25 The Schmidt Reaction, A f The reaction of carboxylic acid with hydrazoic acid in the presence of concentrated sulphuric acid to ‘Schmidt reaction is particularly useful for the Sve primary amine is known as ‘Schmidt reaction. The i et Pepsin of both aliphatic and aromatic primary amines Gig, 1) from the corresponding carboxylic ache tal of te advantage over the related Hofmann ied Courtius reactions that the acid can be used directly tthe necessity of preparing a suitable derivative. ' cH, CH, NH - COOH so” NH, © #0 cH, Pau) cH, Ny C¢Hs—CH2—CH2—COOH a0? CigHls CHa —CH2—NH2 12804 Fig. 1420 This reaction involves the acid catalysed addition of hydrazoic acid 0 carb protonated acyl azide (Scheme-1). This protonated acyl azide then undergoes rear, isocyanate which is then hydrolysed with decarboxylation to give an amine (Scheme-1), The intermediacy of isocyanate in the Schmidt reaction is difficult to establish since, decomposed by concentrated sulphuric acid which is virtually the only catalytic agent ys acids. However, by using a mixture of trifluoracetic acid and anhydride as the catalyst iso with phenanthrene-4-carboxylic acid in high yield (Fig. 2). teeing eC) CF,COOH, (CF,CO),0 f OxyTic ac Tangemeny to isocyanate sed with cyanate wag Fig. 2 The mechanism of the rearrangement is similar to Curtius and Lossen rearrangement. The only dif is the conversion of acid into acid azide in the presence of concentrated sulphuric acid. The reaction well for aliphatic carboxylic acids but less so for aromatic carboxylic acids. However, sterically ki aromatic acids such as 2,6-dimethylterephthalic acid (Fig. 3) and 2.4.6-trimethylbenzoic acid (Fig. 3 give yields. q ° CH, oO CH, I HN, I oa ey ae HO—C COOH Goeensoe HOC NH, ‘CH, cH, CH, CH, HN, HC COOH ase HC ‘NH, ‘CH, cH, Fig. 3 ‘These two compounds undergo Schimdt rearrangement even at 0°C or below 0°C. The above results 8 that initial step of the reaction is an example of unimolecular acid catalysed dehydration of carboxylic Cc I oO i @ Rearrangement Nn; pec 0. R—C==N + R-NH—CHO w 9 9° 9 I cone.H80, | I ROR’ + HN3————> R-C-NHR' + R'"—C-NHR Q) OH | N3H R-CH—CHy—-R——> R—CH7—CH=N—R +) NGH R-CH=CH—R—— R—CH7—CH=N—R 4) Fig. 4 In Schmidt reaction dialkyl ketones are more reactive than carboxylic acids. Th ease of carbonyl compounds the first step is nucleophilic addition of carbonyl compounds with tylavc acid inthe presence of concentrated sulphuric acid as catalysts (Schemes 2-5). Aldehydes: Formation of N-Substituted formamide oO Su OH | 2 Ue Been | 8 “7 == R-C-H Ea | H { HOH oe R—Co | | | H { ee 4 @ Rearrange: ° ay Roomengement | HC=N—R +N, 4 ea Re Gay Ren H,0 cals h H 9° H—C—NH—R <— H— N-Substiuted formamide ‘Scheme-2: Formation of N-substituted formamide422 Formation of nitrile ° Aldehydes 3 eon sug Gu Yes ll HN—NeN |e — C—N—N: rR’ Hu Rr” NH fo. t HoH OH ROH ® face o-# o tpt @ H ROE NA PEN se RCN == eocohe HOH Scheme-3 Ketones: (i) Mechanism in which dehydration of adduct is involved ° 9° OH oH ea e e oped tes pol, RENE acon heen t ROH ou : R-CoR’ OH deyhiaion ROR R—C=N—R N—N=N a Af RoCgN—NeeN I a i, 1 Adduct N=sN at I ° I RI—C—NH=R —R’a MENTS, ov 423 @ Mechanism in which degradation of adduct is not involved. t I le A Ie Sou ou H 9 Rat OH \ @ Rearrange p—GO MN _Rearangement nog ° Scheme-5 the end product is the amide, in which nitrogen has been inserted between the exon carbon and the substituent resent 0 ‘carbonyl carbon, i.e., alkyl group or ary! group. "Tinough mechanism can be formulated (hat om pot involve dehydration and subsequent formality of te inermediate A ot B from the adduct {Scheme:5) there is strong evidence thet these steps take place Je, tetrazoles, which are formed from (C) as “own in Fig. 5 have been isolated as the Inthe case of ketones, (Scheme-4. For exampl Sie poduct. Tis confirms that dehydration ‘of adduct occurs which gives intermediate (© on rearrangement. @ oe @ ReREN-ER+NH-NEN—> nak — ee cau N H lise gn \, ? Fig. 5 The key step, Le rearrangement step in this reaction is'closely related t0 that in the Beckmann rearangement. In reactions where unsymmetrical Ketones are used aS substrates in the Schmidt rearrangement, itisnot suprising, therefore, that the relative proportions of the isomeric amides produced are closely similar ‘b those found in the Beckmann rearrangement of the corresponding oximes (Fig. 6)- R R ‘ o aS \H + o HRD NH ‘0 ba Oe N-OH oOH—N Fig. 6 0 the Beckmann Thos cd Tenaga ketones yield ring expanded lactams and provide oup, irrespective of its a synthetic alternative Als in, E the case of unsymmetrical ketones the larger & nature, tends t0 migrate.424 Alcohcls and alkenes react to form alkyl azides which, under the reaction condit i tion rearrangement to form imines (Fig. 7). Under R or Ree. > on rSc—on HY RS NSN, RZ Rv Fig. 74 7 '23 Curtius Rearrangement os i is i by Curtius The thermal or photochemical rearrangement of acyl aides to isocyanates was discovered BY i i ining bon atom. Th Povies the means for degrading a carboxylic acid t0 2 primary amine containing one ies a eee {es are usualy prepared either by the reaction of sodium azide wih 8 recive aca SBE of Meas of ne erie a specially convient version of the former POSE wpm wih a ra Set a mixed anhydride, which then reacts with sodium azide (Fig. a416 9 ° feb hoy i oy Oe My, oO ° I HNO, | R—C—NH—NH,——25 R-C_N Fig. 1 The reaction can also be carried out on the acid using diphenylphosphoryl azide (Fig. 2). 9 I I RCOOH + (PhO),—P—N3 —> R—C—N3, Fig. 2 yielding urethanes, ureas, esters, attides, etc. and isocyanates are hydrolysable by acid or base into pri amine (Fig. 3). : ° H; A ee oo RONH) #° or 8H |_HOM , R-NH—C—OH 9° 0-1 I R-N=C=0__- BROTH, R_NH- COR” o oO ronntio ly Fig. 3 P is the thermal or photochemical conversion of an acyl az to an isocyanate. Curtius rearrangement is almost certianly concerted.and does not vale! the imrermedie) of a nitrene (Scheme-1). When Curtius rearrangement is carried out in th as styrene, it does not undergo polymerisation, However, there is evidence to support the existence of nit i ic rearrangement to form imines (Scheme-2). Srnecanen aay ally azides R'COOH In the Curtius rearrangement the key stey a ® Hy CAH, C,H,— C—N-P hi ai a = Hr ae Re Niet ENS aes IS, ois CH, cu, Scheme-2 3 eesone ee at7 ‘Scheme-1 nce betw i tween the Curtius and Hofmann rearrangement is that isocyanate can be ‘re essential differe resent and the isocynate cannot islble in Curtius but not in Hofmann. In Hofmann rearrangement, base is pr sanive (Scheme-3): I 4 R-C-N3 ——> —- R-N=C=0 isolable, no nucleophiles present 8 8 =o —2Hs tR-NH + COp + H201 Not isolable, formed in the presence of 84 RONH2 Scheme-3 i ne bf the Curtius rearrangement 4 ‘o the carbonyl group have shown that these re: ‘ich the chiral carbon is directly. cyl azides in whi guration (Fig. of optically active a ‘occur with retention of the confi; sactions CHs t a (@C1I-—C—OCaHs Hs—Cl poh OST Coll —CHy—C—NH2 soir | ‘OOH “iy NaNya * | H Gi) #20 H Retention of the configuration Fig. 4 Thy ing hl centre atached t0 the ebony! BFOUP migrates to nitrogen with its electron but without ‘as been support ind is optically ‘amo i "tmoleeular ed by the azide (1)- nature of the rearrangement bi by eo the presence Geihity gus 8) tan (1) is biphenyl derivative. This comPou418 ORGANI sy, in the ortho position in ring A and B which prevents rotation between C; and Cp. This optically ative 4 gives optically active amine in Curtius rearrangement. If the migrating groups had been completely re product would be racemic mixture instead of optically active due to rotation about single bond betyee and Cy. : Above results confirm the mechanism of the Curtius rearrangement given in Scheme-I4.5.2 The Jacobsen Rearrangement , ‘This rearrangement is given by polyalkylated benzenes, polyhalogenated benzenes and halogenated poy alkyl benzenes. HG CH, Cl cl = CH, Hi, cr : : ‘cl HC 0) CH a Heo Benzene ring should have at least four substituents for this rearrangement. Out of four substituents #!! may be alkyls (1) (mainly methyls) all may be halo, chloro, bromo or iodo) (2) or some may be alkyls some halo groups (3 and 4). o ‘This rearrangement takes place When the substrate is heated with concentrated sulphutic acid. This leadspene 461 srontion ofthe substrate, 1 8 the sulphonic acid formed from these subsites that unde semen (Equation-1). BOCs ce (CH, cH, SO,H HAC, i, 2 H,0/A ‘oC AB OS Sy, ‘CH, HC ‘CH, Hy ‘CH, HC ay 7 CH, CHy (s) 6) rhe sulphonic acid group can be removed easily by hydrolysis, and the overall process results in yrisation of the original substrate. This rearrangement is intramolecular rearrangement which is confirmed rerepemical eatin (1) In this reaction (CH),S0, oF CH;HSO, cannot be isolated from the reaction y He Crearangement will be intermolecular then formation of these products would take place. The ure. went of the rearrangement is given in Scheme-1. Hy (CH; CH,, CH, HAC. SO,H 1,80, @ => so CH, HC CH, ue HC “CH be wy complex x complex Jeon OH ee UHC ‘CH, ‘o-complex (renin ion) } TG SO,H SO, ar HC’ CHy H,C’ ‘CH, Cc" ‘CH, chy oF eH, pee 8 (3 CHy eeomplex complex arenium ion 0) a ( ‘Scheme-1 wpa rearrangement involves’ ipso-sulphonation: followed by intermolecular migration. Intermolecular coon tus by a series of 1,2-nucleophilic shifts. First 1.2-nucleophilic shift produces arenium ion ) hindrance |.2-nucleophilic shift produces arenium ion (10), which is more stable than (9) dus to the steric . = Areium ion (10) leads to the formation of rearranged product. ; of halogenated poly alkylbenzenes migratory group is always halogen (Equation-2). Hy cl CH, CH. CH, (Conc H,S0, Hy CH, 1,80, Goro fy ee << +) "i y 1,076 ot Hy x % ( \ ; «aay ciORGANI g) ‘The most useful application of the rearran; mee oetahydroanthracenesulphonie acid (16). nS Me COmvesION of octahycrope anthrene (15), S0H HySO4/a a as) 06 This conversion takes place as follows (Scheme-2). SO,H, CH cH SO,H H,S0, 1804 Core 12a SO,H SOsH CH;—CH, _— 1H CHy—CHy ‘Scheme-2 4.5.3 Rearrangements of N-Substituted Anilines: Orton Rearrangement © This rearrangement is given by N-chloro and N-bromo-aryl-amides in the presence of HCVCH;COOH or HBr/CH3COOH. When N-chloroacetanilide is treated with HCI in acetic acid and solvent, the chloro group appears to migrate from the nitrogen atom to the ortho or the para position (or both) in the ring (Equation-1). Q ? ‘N—C—CH, NHCOCH, NHCOCH, Cl CG nevcxcoon oY a ea “ss > + ca Similarly, N-bromo aryl amides give this rearrangement with HBr/CH3COOH (Equation-2). Br—N—C—R NHCOR NHCOR Br @ HBeICH;COOH » Br Major product of the rearrangement is para derivative possibly as a consequence of steric hindrance bY the N-acyl group. The rearrangement proceeds by the following path (Scheme-1):463 fast 12 =O £7 ‘Oo : ker. cy orfoste NH—C—R NHCOR c=. io a a) ‘Scheme-1 in the first step, giving (2). Species (2) ed by HCl, the specific catalyst, Free chlorine then (3). This C1® reacts with C19 of HCi to produce Cla. gives electrophilic aromatic uibgticution reaction with( arylamide (3) and gives, 85 usual p- and rpraryamides. The facts supporting this mechanism a (1) Aryl amide (3) and chlorine can be isolated from the reaction mixture, If reaction is carried out while airis bubbled rapidly through the solution, elemental chlorine, Cl2 is found to be carried away, leaving aryl anide (3) in the reaction mixture. (2) The ortho para ratio of the products or Orton rearrangemen ty reacting arylamide with chlorine directly. {@) When hydrobromic acid is used as catalyst ‘is cn oly be explained by the mechanism given in ‘Scheme-1. Nechloroanilide is protonat eliminates CI° and gives ary! amide ig practically the same as that obtained for N-chloroacetamide then p-bromoacetanilide is formed. a NHCOCH; NHCOCH; Cl-N—COCH, H—Ns-COCH, reacting species He. feb & for ArSE. — —_— Cci—Br+ Br up) from nitrogen to the ring carbon is hown by isotopic labelling experiment. place of HCI. e third 10 (i.e, halo gro ent can aso be sl (4) and (5) when HCP is used in for the reaction has been found to be th at result also confirms that migration of chlor rn sl: nemoleular nature of the rearrangem (erp saing material (1), and also in products erie T observed rate law also fits into the Scheme-1, al rale= star —conmtH HCH) ¢ 2 Ks[Ar-N—CORIHCI?®464 ORGANIC svi, 4.5.4 The Hofmann-Martius Rearrangement 2 —— When HCI or HBr salts of aryl alkyl amines are heated at 250 to 300°C, migration of. alkyl Bro nitrogen to carbon of the aromatic ring at ortho and p-positions takes place. This rearrangemen, igh Hofmann-Martius rearrangement. Main product of the rearrangement is p-derivative possibly ag a cone of steric hindrance. e e ‘NH,CH,cI? NH,cI® o ~ cH, @ when para position of the substrate is occupied, the rearrangement takes place at ortho posto (Equation-2). HG CH, Sv HCN cic = oO a GH GH, Cols iy oe f If the alkyl group is capable of isomerisation, it bonds with'the para or ortho position in isomerised fom (Equation-3). This result indicates that the rearrangement is intermolecular rearrangement. 2 NH—CH,—CH—cH, Scie A) A um | cn | 1 Intermolecular nature of the rearrangement is also s\ from the reaction mixture (Equation-4), ‘upPorted by the isolation of poly alkylated product oe)NGEMENTS. poms 465 ny =e oe ° Gyr CH CH, Ane cH, —> + ue Ye ere netmets 0) cl—c—cn—cn, | ue) Hy aD o + CH CH CHC, CHy (13) n of these products of reaction (5) leads to the conclusion that the alkyl group splits off as alkyl Formatiol r halide by heterolytic fission and generates an alkyl carbocation. This alkyl carbocation also undergoes veengementreation. The mechanism which explains all above facts is given in Scheme-1. NU Step-t = +R-Cl Stepll = wc? ‘Step-Ill ° Nt NH, — +H® re re HOR NH, ’ e 45-5 “ ‘Scheme-1 jertiary nce of hydrochloric acid gives para-t Aniline wh fi 7 fh Shane (ig heated with 2-methyl-2-butene in the pre in Scher..e-1. section strongly supports the given mechanism i ee xu, NHAC cH. HC + 1 ome Hye ss y woo cH Hs CH; i4ayO 466 ae 4.5.5 Fischer-Hepp Rearrangement Wwe This rearrangement is given by N-alkyl-N-nitroso aryl amines in the presence of hydrochloric ai this rearrangement nitroso group migrates from nitrogen to the carbon of aromatic ring at ae (para-position in benzene ring (Equation-1). pa ORGANIC SATE R—N—N=0O NHR NO Product of the rearrangement is p-nitroso secondary aromatic amine. This reaction is very useful reaction for the preparation of p-nitroso secondary aromatic amines because this compound cannot be prepared direey by nitrososation reaction of secondary amines. Secondary amines give nitrosamine (Scheme-1). NHR NHR NaNO,/eone. HC x ArSE . ‘Scheme-1 Only HCI gives efficient rearrangement, other acids give poor or no result. This rearrangement is intramolecular rearrangement which is supported by the following results: ( This reaction takes place in the presence of excess amount of urea. This shows that reaction ® intramolecular rearrangement since, if NO or NOCI are formed in the reaction mixture, it would be captured by the urea, preventing the rearrangement. ii) Nitrosyl chloride is neither isolated nor trapped from the reaction mixture. Gi) When methyl phenyl nitrosamine is rearranged in the presence of “N labelled sodium nitriteone HCI, no '5N enters the p-nitroso product. This experiment confirm that the rearrangement is intramolecular fH nature. HC ° NHCH, NHCH, oO = iva =O N= =r i eo N=o ) only wi 5 8 Product (his product {snot formed) Intramolecular nature of the rearran; i \gement can only be explained by the formati is ical pairs. The first step of the rearrangement is protonation followed by homolytic cleava Thi cho aie radical cation and radical pairs are present in tight solvent cage. Rearranged roost ta fortied | ra fhe rapid e467 REARRANGEMENTS. radicals before diffusic Ive mi sior n from the solvent cage. Thus the \echanism ci 1 fan be rep resented recombination of the fe follows (Scheme !)- NHR N=oFaies Rearmenqew ert alain S REARRANGEMENT: + a ecrssunig ee w Ws 7 oe 47 S SVM BY amy estas ot aliphatic oy Promutic casbory| t Act AL iG) where R = alkyl group or aryl group i ic or aliphatic. Esters having chains upto eighteen ‘Thus the acyl residue of the substrate may be aromatic or alip! g - pto cighte: I tons long have been successfully rearranged. The relative rates of rearrangement of R—~C— have been shown to be inthe order of R = alkyl > benzyl > cinnamoyl > phenyl In this rearrangement aryl esters are treated with Lewis acids to give ortho and para hydroxy ketones (equation-1). OCOR OH OH Oo Anhy. AICI on x Q sl) pre OR ‘The acyl group migrates mainly to the ortho position at elevated tem perature but at moderately low temperature, it enters mostly the para position (equation-2). OH o—C—cny, on ae lsc cocH, 1) a pai “Any AIC, Fahy aicle : cocH, 95% 0% This yf 9 seca re se because the para derivative is formed the faster (Kinetic control) but the ortho ™odynamically the more stable by virtue of possessing chelate system. or ier Mv Phenols Si i may be met exter has Coane 2-acylphenols on heating with aluminium chloride, although the temoiyramiegg = Krell consene nee COMltons This resultalso suggests ther pare cee ane Snel consaedprodea me Product whereas ortho derivative wenn rearrangement) is OH OH Ayal * ay, Soe A; Cock, *472 ) ind wheth when esters (1) and (2), itis ing, rent o-hydroxy ketones (3), (4), ) ae hey ©) and at in the presence of anhydrous isolated from the reaction mix ture (Scheme-1). 9cocH, OCOC Hs on oH ch cl i Any. AICI cock, COC GH + is cH, cH, cH, * CH, o @ o° @° OH oH ch He COC Hs cocH, CH, cH, 6 © ‘Scheme-1 Formation of cross products (5) and (6) suggests that rearrangement is intermolecular rearrangemen. Similarly, when ester (7) and anhydrous zinc chloride are heated in the presence of meta-chlorobenzoyl chloride (8) a benzophienone derivative (9) is obtained (equation-3). oon, en Cl ° i ¥ cy primacy a) 3 CH, CHs Formation of the cross product confirms that the rearrangement is intermolecular rearrangement. In the intermolecular rearrangement, in the intermolecular mechanism, the aryl ester and Lewis acid form an adduct which dissociates into an acylcation and an aryloxy —AICl; anion. The former attacks the ortho and p-positions of the anion. Thus mechanism can’ be considered to be an intermolecular electrophilic aromatic substitution reaction (Scheme-2). ele, gfe, &, Te 825.810, Gres —R ‘Scheme-2cas SOMES 473 in mind that, despite the fact that the Lewis acid is a catalyst for the reaction, the ir should by Petpy the rearrangement form complexes with the Lewis acid and so it is necessary to use yng FOIL Ty of reagent fo obtain maximum ST ‘of the product. en regerplectron withdrawing groups on the aromavic ting disfavour or totally block. cording is the case. For example rearrangement does not occur if aromatic ring has a nitro group io ae ha an acyl grOUP at position-4. The presence of ‘acyl group at position-2 completely inhibits 2 oF g position . eas e the reaction- Jar mechanism, the phenyl ester apparently forms an adduct with aluminium chloride in a inamolect Tar process. In this case the acyl SFOUP Tnigrates t0 the nearest ortho position in the adduct (Scheme-3). og e ” 2@—Alcly C—CHy 9 OAICh, 6 rf All H oO =H ‘C—CHy > ‘c—CH; ——> Il I ° rove OH oO C—CHy ‘Scheme-3 Formation of ortho isomer as the major product indicates that the reaction is intramolecular in nature. In cold nitrobenzene p-tolyl acetate does not give Fries rearrangement with aluminium chloride but sidition of thymol gives C-acetylated thymol. OCOCH; CH; CH; COCH; C " Any A ‘OH HO CHy cH cH YN ZN HC CH; HC CH & aie a et mae result Baltzly emphasises that a complex of ester and aluminium chloride can inte sve an i bean a molecule of ester or on a second reactive substrate if present (eg., thymol ives only p-derivative, Baltzl low very well that electrophilic ‘aromatic substitution in phenols or their esters ester on a second hia eae that the. para Fries rearrangement is the result of attack of coordinated intramolecular process havi Le., rearrangement is intermolecular), while ortho Fries rearrangement is an Fri ving a high energy of activation, and so favoured by rise in temperature. ies rearrangemer i gement also takes place under UV light. This rearrangement is known as photo Fries i O—C—R 3 OcoR OH ay CqsOnr, = COR! Solvent cage ‘Scheme-4474 ie. i ORGANIC Sty rangement, i inatic oe ee ment. Spectroscopic examination of the fearrangement indicates that reaction ‘ Re Hate. The free radical mechanism is given in the Scheme-4. Proceeds via rag. 4 ‘ 4 omolytic bond cleavage generates a radical pair. ‘The radical pair is present in tight sol 4 vent cage he solvent cage 4.5.8 Claisen Rearrangement ee Rearrangement of allyl aryl ethers (1) into ortho all . lyl phenol (2) on heating at about 200" Claisea rearrangement (Equation-1), 1B at abor 00°C is known —CH—CH,=CH, 1H ‘CHy— CH=CH, sll) a @ The rearrangement is carried out either in the absence of solvent or in solution in an inert high boiling solvent such as N,N-dimethylaniline. In this rearrangement allyl group gets migrated from the ether ov atom to an ortho position of the aromatic ring. Aryl allyl ethers in which both ortho positions of the aromatz ing are substituted, also undergo Claisen rearrangement in which the migrating group migrates to the para position giving a p-allyl phenol (Equation-2). O—CH;—CH=CH, 1H H; CH, HC CH; a 2 ® CH;—CH=CH, @ A striking feature of the rearrangement is that the allyl group turns inside out during migration, i original y-carbon of the ether side chain becomes attached to the ring carbon (Equation-3). CH, 17 CHs tuba el OH” CH; i \ yl Bp o CH C—CH=CH, 7 4 coc ly CH, © a2 This result has also been confirmed by isotopic labelling experiment (Equation-4). \—CH;—CcH=¢H, OH eee én;—cH= ch, o ty ECE: ” ® The above two examples indicate that it is the carbon-3 attached to the ring. On the other hand, it is the o-carbon atom of the allyloxy group that becomes bonded to the benzene ring in the para rearrangement (Equations-5 and 6). Thus allyl Broup does not turn inside out in the para rearrangement. carbon) of the ally! group that becomesae 478 fab : Ech Hy cH cH, Hy cn; ~ 6) cn er ap YNcH, 0) H Hy ci, be Hs a © af ca ginbn a2 ement is carried out in a nucleophlic solvent like phenol or N, N-dimethylaniline no niles out the ionic mechanism. of the When the rearrang ! allyl carbocation (Equation-7). This result rul product results from the rection. q-cy-CH=CH, OH oH Q—CH;-CH=CH, ‘Oro -O as) cH, “This dots not form. a, o a ‘The Claisen rearrangement is generally not retard: tion inhibitors Fie pieazoquinone, diphenylamine, oxygen or iodine. This result indicates that reaction is not free radical reaction. Intramolecular nature of the rearrangement 1s confirmed b; ied by the addition of free radical react iment. When two different yy crossover experi (20 and 21) are obtained, ters (16 and 17) are allowed to rearrange in the same solution, no cross products caly 18 and 19 are formed (Scheme-1). Q—CHy-CH=CH— Cis O—CH;-CH=CH, 09 | ay CH;-CH=CH, OH ec), - Os cr) a Cos i : CH—CH=CcH, oH eo" : + on en ‘Scheme-1476 ORGANIC SYNTHEG Th i © concerted intramolecular nature of the rearrangement is confirmed by an optically acti ctive ther, i i : sve hon ye sheer) Bement, 7 gr gitelimct—cx, OH CH a Or pr-Hay (2) an? 1 may be noted that a-carbon of the subsrae is chiral carbon. During the rearrangement ann the allyl group gets bonded with the ortho position and after that y-carbon becomes chiral instead of on, Hence optical activity is retained, baton The rearrangement has first order rate law and entropy of activation of the rearrangement is negating (ranging from ~2 to -16 keal per degree). The above results suggest that the product formation takes place by the formation of six membered cyclic transition state, i.e. rearrangement is sigmatropic rearrangement. Tue ortho Claisen rearrangement proceeds via concerted [3, 3] sigmatropic rearrangement which give cyclohexadienone (i.e., ortho dienone intermediate) intermediate (25). a o7-Ch,, 0 OH a1 Deh H eS. CH,—CH=CH, —> CHL CH= CH ly 2 YB a vy Bio (2s) ‘ortho dienone intermediate ey six membered cyclic TS. ‘Scheme-2 Tautomeric’ shift of the labile ortho-hydrogen atom in the ortho-dienone intermediate (25) gives the product. Such keto-enol tautomerism cannot occur in the rearrangement of substrates lacking an ortho hydrogen atom. Scheme-2 ortho dienone intermediate (27) of those substrates which have no ortho hydrogens undergo a Cope rearrangement involving (3, 3] sigmatropic shift to give p-dienone intermediate (28). The p-dienone intermediate then tautomerisers to p-allyl phenol (Scheme-3). 1 CHa, 2 1 or ° RNGH, 3 _ m t A Caisen foc, ty eae . 26) CH, Hg yas ba Ht ° R R R R _— Hy—CH=CH—CH, 1 chy—CH=CH—CHy * enon?) pdienone intermediate Scheme-3eaRRANGEMENTS 477 In para Claisen rearrangement the allyl lyl group is reversed in the first stage and then u d inreversed in the ind stages se mechanistic pathways given in Schemes-2 a s-2 and 3 account ni Ira rearrangem« i icely the pai jgement. Trapping of ortho dienone intermediate ee ees coursegfithe use of Diels-Alder cisen onto and ction confirms the given mechanism (Scheme-4), | —CH, CH=CH, HG CH; Hy i ed ° gin, i ca—e | I ° | ° HAC. = acca | CH 0 cre or a a 0 0 ° o Isolated from the reaction mixture Yosser rion) on 9 HC CH, Il cH-CY aston 0 cH—c% CH,—CH=CH, E ‘Scheme-4 Claisen is i rearrangement is also given by allyl vinyl ethers. Ally! vinyl ethers give y, S-enones on earrangement. ‘yb enone m is usually favourable for product formation ‘er that make it a powerful tool tal-like compounds are used. ers and amides Because th : = ae See is a carbonyl compound, the equilibri a the synthesis of % iin of the Claisen rearrangement of allyl vinyl eth te ue for eee carboxylic acid derivatives. In each case ace sectvely (Scheme 5), and-ketones, ortho esters and ortho amides are used for es‘Scheme-5 Claisen rearrangement is stereospecific with respect to the double bond present in the initial allylic alcohol. In. allylic molecules, the stereochemistry of the product can usually be predicted on the basis of a chair-like six membered transition state. wd — Stereochemistry may arise if there is a substituent on the saturated carbon next to the oxygen atom. In such case, the resulting double bond strongly favours the trans (E) geometry. This is because the substituent prefers an equatorial position on the chair transition state. L¥4 + EAT) E geometry | 1s of allyl alcohols can be rearranged to +, S-unsaturated carboxylic. acids via the o-trimethylsily! tester enolate, This rearrangement takes place under much milder condition than the orthoestt ‘occurs at or slightly above room temperature. i z Esters ether of the ester ¢ method. The reactionpeARRANGEMENT. oO i) 70°C H,C—(CH, yesio- CHIH CH, hn? Se teen th | Sat Eade Gas on Gao H CHy— CHs—COOH Hythe 0 Redanunge ment ef Adiktfone Clit diketo an d Hydrosytersborytte acid tm MON Hu presence of Stwong aa buse © defrag & vale kon o} nefldatemp CH ~ ; 2 \ | Au dificahon oH — = PW. ‘ =5 3) ; 7 [4000 Coon % Meh” is ; . 08 - e ot Jone a = ‘4 4 iN 2 nov == Cre c—0n | jowRDS | Pie abit} a |e ~ “5 HI i i S 1 o i Ee ent Wy a OH 7 7 j a foams 4 — £ = = ht - 0G 6 oe = ity =e St Uf “OF 4; aaTUE 09 oct [pes 2058 - oe tha first sh eis dewensible_cnd Fuser in which + nthe _Corbony carhon +0 give _ 4 _Og4ami0%-1 “Te OX4anien-l_aumden gocs te xute __debenrmining step amd tr 7p O. ph encntheene to gHy}droky -g.cercbo ty ~P NoveMBer 2018 DECEMBER 2018 wEess Mowe ss wt THU OCT 2018 | dd_to Citeie att J Coo cate Ke CooH | o L Cay gens = K aes 3) sy puaiielon Ors aha i je - coal Ba i =6@——t11_______,_. 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