-. First Edition April 2014. » = Second Edition =. March 2015 CAREER ENDEAVOUR PUBLICATIONS has taken due care in collecting the data and providing the solutions, before ‘publishing this book. Inspite ofthis, i'any inaccuracy or printing errots are there, CAREER ENDEAVOUR PUBLICATIONS owos No responsibil, CAREER ENDEAVOUR PUBLICATIONS wil be grateful f you could point out any such emor, Your suggestions willbe highly appreciated, All right reserved by CAREER ENDEAVOUR PUBLICATIONS, No par! of this book may be reproduced or | utilized in any form without the written permission from the publisher. CAREER ENDEAVOUR Publications}PREFACE TO THE SECOND EDITION The book “Organic Reaction Mechanism & Named Reactions” is written with the objvctiv of providing description of principles involved in organic Chemistry including their application at a level suitable for graduate and post-graduate students of Chemistry in different universities. Starting with glimpse of general organic chemistry, the book deals with stereochemistry followed by basic principles of reaction mechanism. Later part of this book focuses on important name reaction and rearrangement reactions. Chemistry of synthetically important heterocyclic compounds is also discussed along with some challenging problems This book will be highly useful for the candidates preparing for various competitive examinations at national and state levels such as CSIR-UGC-NET, GATE, SLET, etc. In all the competitive examinations such as CSIR-UGC-NET/IRE, GATE, SLET, ete, the section ef Organic Reaction Mechanism & Named Reactions carry approximately 10-12 percent weightage of total marks. + Inevery year CSIR-UGC-NETIIRF includes at least 25 to 30 marks from this section out of 200 marks + In every year GATE paper includes at least 10 to 12 marks from this section out of 100 marks. Apart from NET, GATE, PSUs this book will also be very useful to candidates appearing ‘or various Ph.D. entrance examinations. ‘The book is designed and prepared in such a way that it provides the required information regarding almost all important topics. Students preparing for competitive examinations are advised to go through every topic for their understanding and conceptual clarity and then get into solving the problems. For more practice students are also advised to go through our classroom assignments, Much care has been taken to minimize the typographical errors, yet if any noticed, then your suggestions are invited with a view to improve the book in future editions. ‘We would like to thank our respected faculty members for their valuable inputs in the book. Thanks to Mr. Ramashish Paul & Mr. Raj Pandey for their constructive support in doing corrections and proofreading. A note of thanks also to Mohammad Firoz fo: formatting, designing and type-setting the book.Page Nos, Chapter -2 ‘Chapter -4 Kian Chapter -6 Chapter -8 Heterocyclic Chemistry 268-316 eee oaCHAPTER General Organic Chemistry Ll Electron Displacement Effects: Effect occuring due to displacement of electron in organic compound is called Electron Displacement Effect or Electron Delocalisation Effect. Electron displacement effect is of mainly two types. Electron Displacement Effect >— Permanent effect ‘Temporary effect Polarization effect) (Polarizabilty effect) Inductive Hyper Resonance Mesomeric Inductomeric Electromeric effect conjugation effect effect effect Other Effect: (@) Steric inhibition of resonance _(b) Ortho effect. (1) Inductive effects: Ina covalent bond between two different atoms, the electrons in the —bond are not shared equally. The electrons are attracted towards the most electronegative atom. An arrow drawn above the line representing the covalently bonded electrons shifts towards higher electronegative atom can show this. Electrons arepulled in the direction ofthe arrow. When the wom 0 is mace When the atom (Biss electronegative than carton electronegative than carbon electrons attracted toX electrons attracted to carbon +> =<- XO \ —c-x —-z 7/4 7 4 egative inductive positive inductive effect (effect) fect (+ effet) I groups +I groups aGeneral Organie Chemistry X=Br, Cl, NO;, OH, OR, SH, ‘SR, NH, NHR, NRo, CN, COH, CHO, COR, ‘The more electronegative the atom(X), the stronger the I effect Z=R(alkyl or aryl), metals (eg. Li or Mg) The more electropositive the atom (Z.), the stronger the +1 effect. Pauling electronegativity scale The inductive effect ofthe atom rapidly diminishes as the chain fength increase kook Teas the chain fength increases C=23 0 Br=28 N=30 = 3.0 0-35 -F = 40 Higher the value, more electronegative will be atom + 88+ B+ BE HeG—CH— CHa CHa ~ch experiences a negligible ~i effect experiences a strong -I effect ‘The overall polarity ofa molecule is determined by the individual bond polarities, formal charges and lone pair contributions, and this can be measured by the dipole moment (1). Higher the dipole moment (measured in debyes (D)), more polar will be compound. (2) Hyperconjugation: Ao —bond can stabilise a neighbouring carbocation (or positively charged carbon) by donating electrons to the vacant p-orbital. The positive charge is delocalised or ‘spread out’, and this i stabilising effect is known as “no-bond resonance”. TAY CH the electrons in the o-bond e-bond spend time in the vacant p-orbital vacant p-orbital ‘Points te Remember : ‘Number of « hydrogen oc number of hyperconjugating structure o: stability 1 1 «——___________ « Polarity « dipole moment «& — Heat of hydrogenation bond length Problem : The correct order for the stability among following compound is ® ® Hee, Hee, CH;CH, — CHyCH,CH, cH ey Hye SoG, Hye’ tod @ ay qa avy) @IPU>U> IV (E> M>IV>M @IV>M>0>1 @Iv>m>I> 0 Soln, Number of er hydrogen oc stability. Ths, © a a ay ® Hac, HaC, CH;CH, — CH;CH,CH, No Sh yooh Z Hee we ‘Number of a hydrogen 3 Zz 1 0 Stability, [> 11> I> iV Hence, option (a) is correct. isGeneral Organic Chemistry @ Problem : Which is more stable methyl o -D glucopyranoside or methyl f -D glucopyranoside. fi ys OCHs cXH orbital Methyl a-D glucopyranoside Methyl B-D glucopyranoside ‘There is stabilising interaction i.e. hyperconjugation between the unshared pair on the hetero atomand co" orbital for the axial C-X bond in the case of a anomer. thus itis more stable as compared to its @ analogue in which there is no such interaction, Note : Ifoxygenis replaced by carbon, there is no such stability interactionas like as above. Thus, stability can only be decided on steric ground. Thus stability order for such species will be (Stability) OMe (3) Mesomeric effects: Whilst inductive effects pull electrons through the o bond framework, electrons. can also move through the —bond network. A —bond can stabilise a negative charge, a positive charge alone pairof electrons or an adjacent bond by resonance (ie. delocalisation or ‘spreading out’ ofthe elec- trons). Curly arrows are used to represent the movement of = or non-bonding electrons to give different resonance forms. Itis only the electrons, not the nuclei, that move in the resonance forms and a double-headed arrow is used to show their relationship. (a) Positive mesomeric effect: * When a r-system donates electrons, the 7 -system has a positive mesomeric effect (#M effect). \Omnd, \.-_ 8 - mor <~_— aati donates electrons: “4M group + When a lone pair of electrons is donated, the gorup donating the electrons has a positive mesomeris effect. of ® Ne oy 7 donates electrons: 4M group (b) Negative mesomeric effect: + Whena 7~system accepts electrons, the ~system has a negative mesomeric effect (-M efiect). 2 8 Shon <—> Some Se fou 7H Accept electrons: ‘M groupLe General Org: ie Chemistry “The actual structures of the cations or anions lie somewhere between the two resonace forms. All resonance forms must have the same overall charge and obey the same rules of valency. ‘groups generally contain an electronegative atom(s) and/or a n-bond(s): CHO, C(0)R, CO,H, CO,Me, NO,, aromatics groups, alkenes ef, +M groups gererlly contain atleast a fone pair of electrons or am -bondts) In neutral compounds, thete will always be a+M and —M groups(s): ‘One group donates (+M) the electrons and the other sour) accepts the electrons(—M). nivel > ROH CHG +M group —M group Allresonance forms are not of the same energy. In phenol, for example, the resonance form which theintact aromatic benzene ring is expected to predominate, Ger =b bd Asarule of thumb, the more resonance structures an anion, cation or neutral —system can have, the more stableitis, aromatic 2M group ring is intact Inductive versus mesomeric effects: Mesomeric effects are generally stronger than inductive effects. A+M group is likely co stabilise an anion more effectively than a +I group. ‘Mesomerie effects can be effective over much longer distances than inductive effects, provided that conjugation is present (ie. alternating single and double bonds). Whereas inductive effects are determined by distance, mesomeric effects are determined by the relative positions of +M and -M groupsina molecule. Application of inductive effect, hyperconjugation and mesomeric effect: Acidity and basicity: Acids: An acid is a substance that donates a proton (Bronsted-Lowry). Acidic compounds have low pK- values and are good proton donors, as the anions (or conjugate bases), formed on the deprotonation, are relatively stable. Tnwater: os Ke e ° HA + HO === M0 tere, i acidity constant Acid Base Conjugate Acid Conjugate Base The more stable the conjugate base the stronger the acid fees As H,0 is in excess PK, = logo ‘The higher the value of K,, the lower the pK, value and.the more acidic is HAGeneral Organic Chemistry 5) The pK,-value equals the pH of the acid when it is half dissociated. At pH above the pK, the acid exists predominantly as the conjugate base in water, At pH below the pK, it exists predominantly as HA. pH = 0 (strongly acidic) pH =7 (neutral) pH =14 (strongly basic) ‘The pK -values are influenced by the solvent, Polar solvents will stabilise cations and/or anions by solvation. in which the charge is delocalised over the solvent (e.g, by hydrogen-bonding in water) 4 B® @ & & lo 8 HO-HunAuiH—OH, HOM ORIOH, oN HO SH ‘The more electronegative the atom bearing the negative charge, the more stable the conjugate base (which is negatively charged). pK, 3 16 3 48 Mostacidic HF > HO > NH, > CH, increasing electronegativity ‘Therefore, 1 is more stable than H,C®. ‘The conjugate base can also be stabilised by 1 and -M groups which can delocalise the negative charge. (The more spread out the negative charge, the more stable it is) ‘and —M groups therefore lower the pK, , wl +Land +M groups raise the pK, (a) Inductive effects and carboxylic acids: The carboxylate anion is formed on deprotonation of carboxylic acids, The anion is stabilised by resonance (ie. the charge is spread over both oxygen atoms) but can also be stablised by the R group if thishas a—I elect O 0 8 pP. Base ¢ Roce Gas R-Cy <——_ Roo ‘on Basel) ‘Od Ny The greater the effect, the more stable the carboxylate anion and the more acidic is carboxylic aia ~+ + Oc ae, “Sen (b) Inductomeric Effect 5 + Temporary effect. “Takes place in sigma bonded system. + In presence of attacking reagent, transition of'a electron cloud takes place more readily. Example: © ROH + Bo Inpresence ofbase B, movement of sigma electron takes place faster. ) Other Enfect : (a) Effect of inertia/steric inhibition of resonance: Resonance ability ofan atoms lost ifit looses planarity with the other part ofthe system due tosteric crowding bybuiky group in adjacent positions NH, NH. HC. CHs HyC’ ‘CHs NO2 NOz @) @) iqThe above two compounds A and B have everything identical except position of the two methyl group. Itis expected that A should be stronger base than B due to closeness of two electron donating methyl group ‘0 — NH, The fact is opposite to this. In compound B -NO, is surrounded by two bulky methyl group and they sterically sepel the -NO, group. In order to minimize the steric repulsion by the two adjacent methyl group, the nitro group loses planarity with the benzene ring. So, now -NO, due to lack of planarity weigh ring, not able to resonate. This is known as steric inhibition ofresonance, Thus in B ,-NO, is not decreasing basic strength by resonance, InA —NO, lies in the plane of the ring, itis in resonance with the ring, decreases basic strength of -NH, by resonance, hence weaker base. Similarly we can explain the acidic strength of Cand D COOK COOH HC. CH3 HC” ‘CHs NO2 NO» oO @) Cis stronger acid inspite of closeness of two electron donating methyl group to ~COOH, (b) Ortho effect: Ifany group present on ortho position ofthe benzoic acid. It always increases acidic nature of acid because this group decreases outer resonance of the ring toward acidic nature. Similarly ffany group present on ortho position of aniline, it decreases basic nature. This effect is known as ortho effect. Problem : The correct order of acidity among the following compound I-IV is Or OL 'NO2 No, @O ap ay (iv) @U>M>IV>1 ()IV>I>II>1 (I> IV>m>1 (@IV>mI> > 1 Because of ortho effect o-nitro benzoic acid is most acidic followed by para and meta. Thus order willbe it > IV > III> 1. Hence, option (¢) is correct. Keynotes in Organic Chemistry: + I£-M groupsare introduced at 2-,4- and/or 6-positions, the anion can be further stabilised by debcalisation through the system , as the negative charge can be spread onto the-M group. We can use double- headed curly arrows to show this process. + If-M groupsare introduced at the 3- and/or 5-positions, the anion can not be stabilised by delocalsation, as the negative charge cannot be spread onto the-M group. There is no way of using curly arrows to delocalise the charge onto the-M groups. + If-1 groupsare introduced on the benzene rng, the effect will depend on their distance from the negative charge. The closer the I group isto the negative charge, the greater the stabilising effect willbe. The order of-Istabilisationis therefore 2-position >3-position>4-position, + The—Meffects are much stronger than I effects, eq =General Organic Chemistry Example: The NO, group is strongly electron- withdrawing; —I and —M. HO OH On oo Nop ‘NO 4 pK 99 84 Least acidic ss 0-Lor-M The NOpcnonystbilse froupson he rng theanion ndacve'y “The NO, can only stabilise the anion induetively and ar NO; NOz 40 Moet acidic as both NO, groups in stabilise the anion induetvely and by rexonance Bases: A base isa substance that accepts proton (Bronsted-Lowry). Basic compounds have high pK.- values and are good proton acceptors, as the cations (or conjugate acids), formed on protonation, are relatively stable, In water: es Kk ® ° Bo + HO === BH + HO Base Acid Conjugate Conjugate Acid Base ‘here, Ky is basicity constant ‘The strength of bases are usually described by the K,-and pKa-values of the conjugate acid. Ky ® @ BH + H,0 B + H;,0 (a][2,0"] Pee [ ® [a5 #,0 isin exces] where K, is acidity constant. ® + IfBisastrong base, then BH will be relatively stable and not easily deprotonated. BH will therefore | have ahigh pK, -vahie ® © + [fBisaweak base, thenBH willbe relatively unstable and easily deprotonated, BH will therefore have alow pK -value, ‘The cation can be stabilised by +I and +M groups, which can delocalise the positive charge. (The more ‘spread out’ the positive charge, the more stable itis). on Inductive effects and aliphatic (or alkyl) amines: On protonation of amines, ammonium salts are < © © Ro ea RNHs X | &General Organic Chemistry ‘The greater the HI effect ofthe R group, the greater the electron density at nitrogen and the more basic the amine. The greater the +1 effect, the more stable the ammonium cation and the more basic the amine, He Be NES HON-H ERONGH BRON—H EP -N—H / / / / H H H Hf pK, 93 10.7 10.9 10.9 ‘The pK,-values should increase steadily as more + alkyl groups are introduced on nitrogen, Howeves, the pK,-values are determined in water, and the more hydrogen atoms on the positively charged nitrogen, the ‘greater the extent of hydrogen-bonding between water and the cation. This solvation leads to the stabilisation ofthe cations containing N-H bonds. Inorganic solvents (which can not solvate the cation), the order of pK sis expected to beas follows: R,N > R,NH > RNH, > NH, (R= +I alkyl group) st base les bse ‘The presence of -I and /or ~M groups on nitrogen reduces the basicity, and hence, for example, amides are poor bases. Ethanamide has a pK, of -0.5, qG ni ‘The C=O group stabilises the lone pa on aitogen by CRS, ~~ —* -_Cx® resonance. Ths reduces the HsC7 [WH HgC7 “Sip Geeton densiy on nitogen Mt (@) Mesomeric effects and aryl (or aromatic) amines: ‘The lone pair of electrons on the nitrogen atom of aminobenzene (or aniline) can be stabilised by the delocalisation ofthe electrons onto the 2-, 4-and 6-positions of the benzene ring. Aromatic amines are therefore less basic than aliphatic amines. @ ® © NH, NH, Ny Cf bbb. * GS + If-Mgroupsare introduced at the 2-, 4-and/or 6-positions (but not at the 3- or 5-position), the anion can be further stabilised by delocalisation, as the negative charge can be spread onto the-M group. This reduces the basicity of the amine. + f-L.groupsare introduced on the benzene ring, the order of I stabilisation is 2-position > 3-position> 4- position, This reduces the basicity ofthe amine. Ni, HAN i, NO2 NO2 pK, * 46 245 028 Most basic 28 no-T or-M ‘The NOp group can stabilise the __—_—LaBst basic: The NOp group can stabilise groups on the cing lone pair inductively the lone pair inductively and by resonanceGeneral Organic Chemistry + If+M group (e.g. OMe) are introduced at the 2-, 4- or 6-position of aminobenzene, then the basicity is increased. This is because the +M group donates electron density to the carbon atom bearing the amine ‘group. Hohl NH, Holi OMe ‘OMe Meo pK, 42 45 5.3 ‘Most basic: The OMe group can donate electron density tothe nitrogen and it has a weak I effect (aswell. apart from the nitrogen) Least basic: ‘The OMe group cannot donate electron density t the carbon atom bearing the nitrongen The OMe group can donate electron density tothe nittogen but ithas a strong effect as itis in the 2-position Curly arrows canbe used to show the delocalisation of electrons onto the carbon atombearing the nitrogen, iit, iit, iin, lO eleton density — a ‘sicentoue alpen eres ewe ‘OMe @0me @OMe (©) Lewis acids and base: + A Lewis acids any substance that accepts an electron pair in forming a coordinate bond. Examples inelnde HBF, AICI, TiCl,, ZnCl, and SnCl,. They have unfilled valence shells and hence can accept electron pairs. + A Lewis base is any substance that donates an electron pair in forming a coordinate bond. Examples include H,O, ROH, RCHO, R,CO, RN and R,S, They all have a lone pair(s) of electrons on the hetero atom (0, NorS) (0 Basicity and hybridisation: ‘The greater the ‘s’ character ofan orbital, the lower is energy the electrons and the more tightly the electrons are held to the nucleus, The electrons in an sp-orbital are therefore less available for protonation than those in an sp?- or sp'-hydrid orbital and hence the compounds ate less basi. most basic: R;N > RC? least basic © most basic: RC > RC sp sp? least basic sp (25%) @3%s) 60%)CHAPTER Aromaticity Introduction Aromaticity isa chemical property of organic compound, aromatic compound have following characteristies @_Ithashigh degree of stability (i) It shows electrophilic substitution reaction rather than electrophilic addition reaction. Itmeans it does not, decolourise bromine water solution. (i) Aromatic compound follow Hilckel rule. According to which A cyclic planar conjugated species having (4n+2)r electrons (where n=0, 1, 2,3, ...) is aromatic in nature. () Theresa diamagnetic ring current. (¥) Each carbon mast be sp*-hybridized or sp-hybridized. (vd) Ithas high degree stability due to filed bonding molecular orbital. Oo 400 4142-60, 4x0#2-28 4x142-6n 4x1+2=6n (Aromatic) (Aromatic) (Aromatic) (Aromatic) Forexample: igh Degree of stability: High degree of stability is associated with resonance energy. The compound which ‘have more resonance energy is more stable. The compound which have more potential energyyis least stable. 1 Aromatcity ce Resonance energy (R-E) ac Stability c: ‘Potential Energy(PE) Greater the resonance energy higher willbe the stability of compound, Resonance energy ofsome aromatic systemare given below as 2O000 21 keal/mol 29 kcal/mol 16 kcal/mol 36 kcal/mol 32 keal/metAromaticity (3) Presence of diamagnetic ring current: Aromatic compounds show diamagnetic ring current due to paired electron. | Facog (60) HH, where, Hy ~extemat magnetic felé i Fane = HAH , ~induced magnetic field A, Clockwise direction in electron present for aromatic compound. Deshielding region (igh 5 value) ae oy 47 deshielding region (down field) t a 11 shielding region (up field) % Aniacomatc comping ——_ —— > Deshiclding region Shielding region #765 4327 0 5 value—sp*> sp > sp? (decreasing order) due to anisotropic effect. + Molecule in which outer protons are deshielded and inner protons are shielded is known as diatropic molecule, These type of molecules are always aromatic in nature. Similarly, molecule in which inner protons are shielded and outer protons are deshileded are known as paratropic molecule. Paratropic molecule is aromatic in nature. ‘Antiaromatic compounds show paramagnetic ring current due to unpaired electron. Q oS \ == ‘ N \) H. H Il Pa HNC _| ! 4 H LY "\ t N | —~ Highly shielded proton a ¢ = (low 5 value) oO oO” OdAromaticity 3 Hiickel Rule: This is a very popular and useful rule to identify aromaticity in monocyclic conjugated com- pound, According to which a planar monocyclic conjugated system having (4n +2) delocalised (where, n= 0, 1,2, .».) electrons are known as aromatic compound . For example: Benzene, Naphthalene, Furan, Pyrroie ete. ne (4x0 +2) we (421+2)z6" =6ne n=2 (4%242)me" =10e~ n=3 (4x342)ne" =14ne" n=4 (4342) ne" =1876" + Craig's Rule: This rule is applicable for polyelic non-benzenoid compounds. If molecule contain C;-axis then count total number of double bonds (N) and calculate value of N-1 which decide aromaticity in compound, (Jf N-1=0dd, compound is non-aromatic (2) fN— 1 even, compound is aromatic. eg. Azulene resonating N-1 =4n bond (aromatic) + Insystem C,-axis must be present Cyaxis 1 — —CD—-C> (non-aromatic) — N=4 , odd. Hence, compounds non-aromatic. O-CO-OO (eptatene) (non-aromatic compound) N=6 =5, odd. Hence compound is non-aromatic. + Pentalene and heptalene is a non-aromatic compound, Since it does not follow craig’s rule + The organic compound which show aromaticity are aromatic in nature or diatropic in nature and th (outside the rings) signal always exist away from the TMS (these protons are dishielded protons) + Identification of aromatic, anti-aromatic and non-aromatic compounds.Aromaticity ‘Organic Compound (1)AromaticCompound —_(2) Anti-aromatic compound (3) Non-aromatic compound (a) Huckel rule 4n ne” delocalized restriction of delocalization me" (i) Monocyclic system n=1,2,3,4,5, (i) Polycyclic benzenoid Ane (b) Craig’srule n=2= 8ne Polycyelicnon-benzenoid. = n= 3 = 12 ne system planar (sp and sp*-hybridized) (system conjugated) sp? non-planar structure sp? hybdridized carbon atom insert sp’ restiction of ne~ ‘conjugation —> XY? COT (Cyclooctatetraene) Tub shaped (aon-aromatic) + Order of stability and order of resonance energy: Aromatic>Non-aromatie> Anti-aromatic. Calculation of x-electrons: During -electron count double bond count 27: electron and triple bond count 2m electron. Also, lone pair in conjugation is also counted. meal {3 3 oO Lép2e 6ne(4ne + | lp) Gne" (4ne +1 lp) 6ne~ (4ne +1 lp) species in which lone pair is not in conjugation can not be counted: Z Les | Ce : Se hybrid eg. S ASA yp hybridized ~~ sp? hybridized N Lone pair which participate in conjugation system and follow Hiickel's rule ae called Hiickel one pair while which lone pair does not participate in conjugation are known as non-Hiickel lone pair. Non-idekel 1) entte bon —— (Non-Hackellone-pair because bond 2 alcoon Semon i osen| Jone pair of nitrogen is not present (non-Hiickel (cabana) eer at pecipbery. double bond) ana Resonance Structure qiAromaticity [Non-Huckel double bond i 14x elton (Aromatic) 4 carbon = 14 election (Aromatic compound) Resonance Structure + Energy level of aromatic and anti-aromatic compounds can be shown by using frost circle or diagram. Energy levels of regular planar polygonic molecules with an even number of atoms form a symmetrical pattern as shown below. { Antibonding energy level ane { Bonding energy level Ifall bonding energy levels are filled then itis aromatic [Hiickel criterion also required] — — w1.80p — — «0456 — — ap — — att258 — «tp — asap 8 9 — «2p — — 1808 — = wt41p = : a eS =" aiossp — — att4ip — = atl s3p — _ai2p — —at2p Figure : HMO energies for conjugated planar ring systems of three to nine carbon atoms.Aromaticity te Anti-bond Do -- 0A oe 2n electron ‘Non-bonding sp? “me ; ‘energy level 7 Co \ Ay~ Ao AoA ‘4r electron oo 7 (Anti aromatic) eaicctaee level Frost Diagarm for Cyclopropenyl system + Anti-aromatic compound behaves as a biradical + Inanti-aromatic compounds two unpaired electron are present which are all paired. + Oxygen also behave as biradical and triplet state. + Carbene-triplet state are biradical ‘Types of Aromatic Compounds (A) 2n-electron system. (i)It follow (4n +2) ne” system. (ii) electron delocalised then compound is aromatic. (iii) Ifelectrons not delocalised then compound is non-aromatic iv) Compound will never be antiaromatic. Examples: ® g Q ° o&=A wfe = Jo 2 OO oA=A “Avnatic Aromatic Anti-aromatic Anti-aromatic ® ® OO OO weet (anti-aromatic) 2 OH o, 9 hy) | o ‘oH o ‘0 G A R @ (Aromatic compound) Displacement of electrons takes place towards higher electeonegative atom.Aromaticity (B) 4n-electronic system: (@Belongsto 4n xe” system doesnot follow Hiickel rule. (ii) [felectron is delocalised then compound is antiaromnatic. (ii) Ifelectron does not delocalised then compound never antiaromatic (iv) Ifelectron does not delocalised then compound is non-aromatic. ° @ O oA © of] (} A.a- “.. Anti-aromatic ss KA AA + (©)6r ebectron system: Examples: (i Belongs to (4n +2) ne" system. (ii) Helectronis delocalised then compound willbe aromatic. ii) Ifelectron does not delocalise then compound must be non-aromatic For example CH, AH OSes Or LOO CH, 6 e [G}-Fe(co), —> re O —Fe_,. ie = lo A A 6m e° system A (D) 8r electronic system : (Belongs (4n) ne" rule (ii) Ifelectronis delocalised the compound must be anti-aromatic (i) electron does not delocalise then compound is non-aromatic. W ca Tub shaped ‘Non-aromatic Anti-aromaticAromaticity (B) 10x electronic system: () Belongs (4n +2) me” system. (i) Ifelectron delocalised then compound aromatic in nature. (ii) Ifelectron does not delocalise then compound will be non-aromatic. (iv) Compound never be anti-aromatic. A 7 (Repuision between H-hydrogen atoms, causes the compound Lt J tobe non plana. So, compound is no-aromate) (Non-aromatic) We" system Cycisation Bridging Dehydrogenation > ‘Aromatic XC,N,O Aromatic os LN, 10ne" system somatic CD — CO- OD (10m €° system) * Azulene’is the isomer of Naphthalene + Aaulene is less stable than naphthalene + Azulene gives electrophilic substitution reaction + Five membered ring gives substitution reaction (because small siz, electronegativity) 3 oH oh : oH a like (same) charge must be at maximum distance and opposite charge must be at minimum distance for stability resonance structure, (F) 12 % electronic system: (i)Belongs to (4n) re" system (i) Ifelectron is delocalise then compound is anti-aromatic (il) Ifelectron does not delocalization then compound will be non-aromatic, (iv) Compound never be aromatic aqAromaticity cavity size small > repulsion ron-planar > non-aromatic 12ne a S OS (AL ci N,O AA 12ne” system-(non-planar) #5" aromatic, ae ] \ 2K aromatic S (G) 14x electronic system: (i Belongs to (4n+2)zte” system (ii) Ifdelocalize electron then the compound is aromatic (iif) electron does not delecalised then the compound non-aromatic (iv) It never be antiaromatic. Aromatic Aromatic Aromatic ANF a S nonaromatic pheneline Phenelone ion a (aromatic)6. Aromaticity Phenelene is acidic in nature why? Proton (H") remove from the phenaline and acidic in mature and system gain aromaticity. S-F {14 electron system) (BH) 167 electronic system: (i) Belongs to 4nre™ rule, (i) Ifelectron is delocalised then compound is anti-aromatic. (iii) Ifelectron does not delocalised then compound will be non-aromatic (iv) Itnever be aromatic. Dishielded (6-value high) \6re(Anti-aromatic) (1) 18 7 electronic system: (6 proton highly shielded) H | (double bond) Jo“s 4 [18] annutene 18ne" (aromatic) Completely conjugated monocyclic system called annuilene + 18 Annulene contain 3 cis close bond. coca Other Aromatic System: Fased ring aromatic. triafulvalene calicene qAromaticity + Such type of systems is aromatic or non-aromatic but never be anti-aromatic + Ifsuch type of system is aromatic then both ring must be aromatic after displacement of camman double bond. Otherwise both ring will not be aromatic p<] PR a | Pd PM pe pe AA A A ‘overall system nan-aromatic ‘overall system aromatic ‘overall system — non-aromatic Resonance energy of some aromatic system: OOOO 29 kcalimol 16 keal/mol 36 keal/mol 32 kcal/mol 21 tat Pyrrole is called as super aromatic compound 00 8 36- Smt g 67! forC-atomenerey. (tai C-atom) 5 1.2 per C-atom According to electron density at per C-stom, pyrrole is electronically rich. So, pyrrole gives electrophilic substitution reaction more easily than benzene. Electrophilic substitution reaction oc —————1____ resonance energy (aromaticity) ‘Quasi Aromatic Compound: These are generally ionic aromatic compound OH + Clog cS OF : ENa Nu + HCIO, ——> ‘Quasi aromatic compoundAcomaticity cl + NOS F a + AgNO; ——» + AgCl A + SbF; —> A (Quasi aomatic compound) Allotrops of Carbon: (Diamond (i) Graphite (ii) Fullerene Allotrops of earbon a Diamond Graphite Fullerene se hb { = a | Non-aromatic aromatic gives Aromatic gives addition reaction addition reaction Unstable (stable) (non aromatic) 22+ Aromatic) honge Dicimond >Graphite AH =-ve Hate + Tyiamond, AH =+ve (Stable) 242-5 (Unstable) Organometallic aromatic compound: Ferrocence —_Dibenzene chromium Fe Cr + Mesoionie Compound: Sydonsis the first meso-ionic compound which show aromaticity + Meso-ionic compound gives electrophilic substitution reaction + Meso-ionic compound also known as internal salt. & Jr i @ | \, _-0 (Sydons) + Homo-aromatic compound : Compound that contain one or more sp'-hybridized C-atomina conjugate cycle but sp’-hybridized carbon atomare force to lie almost vertically above the plane of the aromatic system known ashomoaromatic compounds. Ha H He + HS, ——> nl ). He " Hd lomrpylim Homotopslivm ——ormoopylimy cationAromaticity ava NaN CHCl GHsOH™ K Bu HM HOM a bb Na -—~| B>C. Which of the following compound is more stable, ® eo Oe) OQ @3 Soin, Soln, Which ofthe fotiowing compound is more anti-aromatic e 2 oA @ GO ° @ A (More anti-aromatic because more planar) The anti-arornatic compound have tandeney to adopt the non-planar structure to maximize its stability Which ofthe following compound gives H,-gas with metal. @| & O (both O--©) 10m electron system O-8=O 10" (planar) H acidic | Acide + Yel H OK SS (Cyclopentadienyl) ‘Aromatic (eyelopentadienyl anion) NA. Cyclopentadiene is acidic in nature due to aromatic character of cyclopentadienyl anion. Which of the compound have more dipole moment. Ae —K A aq ‘Maxiraum charge separation— maximum dipole moment because = qd, where, q=amount of charge, d = distance between two poles. (QD have more dipole moment than (11) ‘Which of the following reaction takes place. ot OO (Non-aromatic) —_(Anti-romatic) {Reaction is not possible because stability decrease} SN! > +L Ye because 2° carbocation form. (non-aromatic) (aromatic)Aromaticity 7. Which ofthe following compound gives geometrical isomerism. For geometric isomerism: At this carbon for both group must be different and C-C bond rotation must be restricted. 0 tio ects «iy bo C-Crotation possible Non-aromatic. 8. Which ofthe following compound is best hydride donor. OC. Q wh we Me le @ “Oe QO the the 9. Which ofthe following compound gives ppt. with AgNO,, Br Br ; “aD eA Soln. (and (i) Br + AgBr ——e Ol QO + AgNO; > O + AgNOs} LA) . ow (Quasi aromatic compound) 10, Arrange these molecules in correct order of deprotonation. D> O-—-De Soin. (ii)>Gi)>Aromaticity Soln. More acidic: ° ° ° ° H ase . H tase 5 H H ° 0 0 ‘O Stable de to resonance Mate the following Column-I Li @) ®) re ° of] 2 of 1O A-(), (iv); BH), (iv), Ci), D-(i)) ‘Match the folloiwng Column-L 4 A ar ie COHN tn | H Stable due to resonance ‘Column-It (Aromatic ii) Anti-aromatic (ii) Non-aromatic (iv) (4n +2) ne" Colamn-it (Aromatic il) Non-aromatic Gi Anti-aromatic (iv) HeterocyclicAromaticity eL | Soln, A-(i), (iv); B+), (iv); C-G), (iv); D-Gi); E-Gii) | HOSO;F 13. SoPs, SO;CIF CO;CHy _agee Inthe above reaction, Ais (@)Antiaromatic —-—(b) Homoaromatic__(c) Non-aromatic Soln. (b) (@) AntiaromaticCHAPTER Stereochemistry Stereochemistry : Tt involves the study ofthe relative spatial arrangement offatoms within the molecules Dynamic stereochemistry: Dynamic stereochemistry is the study ofthe effect of stereochemistry on the raie ofachemical reaction. First Stereochemist — Louis Pasteur (1849 Significance of stereochemistry: One of the most infamous demonstration of the significance of stere- ochemistry was the Thalidomide disaster. Thalidomide is a drug was first prepared in 1957 in Germany, prescribed for treating morning Sickness in pregnant women. It was discovered that one optical isomer Le, R- Jsomer of the drug was safe whereas the S-isomer had teratogenic effect, causing serious genetic damage to early embryonic growth and development. o Q ul / 0 Os i ° S-isomer Reisomer Drug for morning sickness in pregnant women, Teratogenic effect (Remark: In human body, Thalidomide undergoes racemization: even if only one of the two stereoisomers is ingested, the other one is produced } Now we have another example - Propanolol. R-Propanstt (contraceptive) $-Propanotol (ansibyperensive}Stereocheristry SOME TERMINOLOGY Optical activity: The term optical activity derived from the interaction of chiral materials with polarized light. Scalemic: Any non-racemic chiral substance is called Sealemic. + A cchiral substance is enantio pure or homochiral when only one of two possible enantiomer is present. + Acchiral substance is enantio enriched or heterochiral when an excess of one enantiomer is preset b the exclusion of the other. Three terms are used f0 designate a carbon atom bonded tetrahedrally to four different substituents i eh molecule, (a) Asymmetric atom (LeBell & Vant Hoff for an atom attached with different groups). (b) Chiral centre (©) Stereocentre. Asymmetric atom: ‘Compounds with one such atom are truly asymmetric as they lack symmetry. For example Asymmetic atom CH" Noclement of symmetry SAL isprseat inthe motel Sea oa % However, there are molecules which also have atoms with four different substituents and whiehialza bave various symmetry element including plane of symmetry as in mesotartaric acid. COOH Asymmetric centre fon —+ Plane of symmetry =} on Asymmetiecente-—~ QOH ‘Two asymmetric center but also plane of symmetry. Chirality is a geometric property which influences and affects all parts ofa chiral molecule. Stereogenic centre or Stereocentre: A stereogenic centre or in short a stereocentre isanatom having groups of such nature that an interchange of any two groups will produce a stereocentre, f 2 > OH Ho faeces ond-t owen Hon Da ; Hie HOH Ig 3. CHOH S.form Reform + Acarbonatom that is a stereocentre is also called a stereogenic carbon. Conformation: Structures that can be interconverted simply by rotation about single bonds are conform- tion of the same molecule. For example: 4 HH Kesh QW 1H H Hey HH Staggered conformation __‘Eclipsed conformation Note: These two are the conformation of ethane arises due to rational possibilites across C-<-c single bond. Configuration: Structures that can be interconverted only by breaking one or more bonds have different configuration and they are stereoisomers specifically known as configurational isomers. SStereochemistry Isomers Constitute same Stseoiomers > Chain isomerism Position Tsmerisn os > Metameris t Conformational omer Configurations Isomers > Taos + Valence Isomers r ae Ae vero single bond cots 9 es HA Teac 0 ae (or Umbrella inversion) iN i Conformational Isomer (conformers) ‘Configurational Isomers Contigurational Configurational Enantiomers Diastereomers Conformational Isomers - Conformational Conformational ‘enantiomers diastereomers \ nciomer: ast “These Wb ae eationers These to are diastereomers 4 4 H 7 4 " CH Hye H CH CHs @ s So, (A) and (S) are mirror image of each other as shown below H i 4 4 wot ow H om Eye 4 CHs CHy So, these two are conformational enantiomers‘Stereochemistry L 2 Gh, H Now, H. H ‘er H 4 wNtA.ci, CH Hs I stg Since, Iand I are not mirror image to each other so these two aré conformational diasteromers. Ss SS . a XS Conformational diastereomers Structures that are not superimpossible on their mirror image, and can therefore exist as two enantiomers are called chiral. Essential criteria for a molecule to be chiral. There is no any single criterion. There must be lack of element of symmetry. Note: [t isnot necessary and sufficient condition because there are some set of molecules which have some element of symmetry still they are optically active. For example, re Hck Q au a Ck Cz Optically active but having C,-symmetry, ‘The carbon in the molecule should be attacked to four different groups. Itis not a necessary and sufficient condition also because we have an example in which carbon have four different groups but iis still optically inactive. For example: coo ‘Two asymmetric centre but still optically in active owing to plane of symmetry. ‘On the other hand we have also an example in which there is not any chiral centre but still moleculeis optically active. For example: Properly substituted allene Br Br We re cnStereochemistry ‘Not any chiral cenise but stilliis optically active Remral This compound is optically active not due to chiral centre but due to chiral axis, ‘There should be an absence of plane of symmetry. SYMMETRY ELEMENT Asymmetry element is a geometrical entity such as a line, a plane, of a point with respect fo Whichone or more symmetry operations may be carried out. Symmetry Operation: Asymmetry operation is the movement ofa molecule about the symmetry element in sucha manner thatthe resulting configuration ofthe molecule sindistinguishable Srom the original molecule. The molecule may assume.an equivalent configuration or an identical configuration. Group Theory: Mathematical study of symmetry is called group theory. Symmetry element Symbol ‘Symmetry operation Axis ofsymmetry c, do C, Alternating axisofsymmetry S, dos, Plane of symmetry o doo Point ofsymmetry or centre of syinmetry i doi Tdentity E doing nothing, Various types of elements of symmetry are explained below as: (A) Axis of symmetry: An imaginary axis passing through the molecule, rotation on which by 9° gives an equivalent orientation of molecute, tis denoted by ‘n’. Where,n=1,2,3,4, Orientation: Orientation is three dimensional distribution of atoms and groups of molecule. For example: i\ aN wy a ore aes Initial orientation, Equivalent orientation Adentical orientation 360° So, the order of axis Cy = gis? ie. C, (pronounced as C-two) ‘Two things do an axis of symmetry. ee Axis of symmetry ——] L_y Interchange For example in H,0.Sereochemistry is of syeumetry Principal axis Subsidiary axis axis Axis other than Axis of highest Drineipal axis, ‘order Let us consider another example of NH. Vv Neu cs Nonny 7 Nils —— yr yin ‘These two ate identical ‘configuration ‘configuration . N., ys <2 a We HO, Hy Let us consider an example of BE, In BF, one C,-axis is passing through B-atom which s perpendicular to the molecular plane F fy F F, ito! ge Po \ a B B. os, N FL Fy F/ Fy FL Fo Identical Configuration BF, molecule has also 3C, axis. (1) Passing through B—F, bond and interchanging F /F, (2) Passing through B—F, bond and interchanging F/F,. (3) Passing through B—F, bond and interchanging F These three C,-axis can be represented as Fy \ CBF) B. rf FaStereacemisty (B) Plane of synumetry: Imaginary plane passing through a molecule which can bisect the molecule into two mirror image halves. Bisect ‘There ace two functions of a plane — L Reflect For example: () bisecting oxygen ator and reflecting H/H, (i Bisecting all three atoms. O, 9, Og 47D yp HH, (ii) Ammonia have three plane of symmetry. (1) Bisecting H,-N bond and reflecting H/H,. (2) Bisecting H.-N bond and reflecting H/H,, (3) Bisecting H,-N bond and reflecting H,/H,, ym ottisN) Neorg, GB) HY a Hg Hy Hp (iv) BR, is four plane of symmetry. (1) Passing through F,-B bond and reflecting F/F, (2) Passing through F,~B bond and reflecting F /F, (3) Passing through F,~B bond and reflecting F/F, (4) Biseoting all the four atoms viz F, F,,F,and B. (C) Centre of symmetry: A centre of symmetry is a point from which lines, when drawn on one side and produced an equaldistance on the other side, wil meet identical point in the molecule. For example: 2, 4-dimethylcyclobutane-1, 3-dicarboxylic acid Centre of symmetry) CHy Centre of symmetry ‘Now, we want to discuss symametry element of cyclopropane for the purpose of optical activity. Cyclopropane have one C, axis and three C, axis and four plane of symmetry,Stereochemistry Gs axis is passing through centre of triangle and perpendicular to all the three C,-axis, f Cyraxis Hy Ik Hy He 3C axis, 3 2 He Hs (a) Passing through, and interchanging C/C, or H/H, H/H, and HH, (b) Passing through C, and interchanging C/C, of H/H,,H/i3,, Hi, (©) Passing through C, and interchanging C/C, or H/H,, HH, and H/H,. 4 plane of symmetry. (a) Bisecting H, —Cy—Hg and reflecting C,/C,, H,/H, and H/H,, (b) Bisecting H;—c,—H, and reflecting C/C,, H/H,, H/H,, {© Biseoting Hy —Ca—n, and reflecting C /C,, 11/11, HJ, (@) Bisecting C,, C, and C, and reflecting H/H,, H,/H, and H/H, Now, we want to make cyclopropane molecule chiral for this we will have to remove all plane of symmetry from cyclopropane molecule. Because for & molecule to be chiral, plane of syrametry should not be present. Case J Mono substituted cyclopropane a a XK He/IN He Hs. Hs, Ithas plane of symmetry bisecting CILC-H, and reflecting H/H,and Hl, So, this molecules optically ~hyi Case IT: Homodisubstituted cyclopropane S a aia \/ MA “4 H Plane ofsymmetry — Plane of symmetry >No prea > Achiral ~>Achiral ~ But Cy-symmetryis present > Optically inactive > Optically inactive ~ Chiral molecule + Optically ative. Case IIE: Heterodisubtituted cyclopropane Hy Y. =k Br. a. a Bs, a a iy H « oer HM 7 = EN Sw NA jr : H 4 ~ Plane of syrimetry is present , > Noplane of symmetry >No plane of symmetry > Achiral > Noaxis of symmetry —>Noaxis of symmetry > Optically inactive Chiral Chiral > Optically active => Optically activeStereochemistry Case - II: Trisubstituted cyclopropane, cl cl a a Br 4 4 Br 4 ~+Plane ofsymmetry present. Plane of symmetry present > Achiral —Achiral > Optically inactive. + Optically inactive H @ 7 Br Br “fe H a Br i a > Plane of symmetry present > Noplane ofsyrmmetty > Noaxis ofsymmetry Chiral > Achiral > Opticaity active Problem: Find out which of the following molecule is optically active. Br ~ &, F cy, wT N70 ‘Symmetry properties of cyclobutane. Hy be : 2 He 7 h, . 3 He Hy Cyclopropane have one C,-axis and 4Cy's axis, 4o,'s and one o,. C,-axis passing through centre of square and perpendicular to Cy! s axis, Cr—Cp {-[ Cy—C 4C;s axis, (a) Passing through C, and C,, and interchanging C/C,, Hi /H, H/H,, H/H,, H/H,. (0) Passing through C, and C, and interchanging C, and C, H/H,, H/H, Hi /H,, AJ, (c) Passing through C,-C, and C,-C, and interchanging #1/H,, H/H., H/H,, HJ, (@ Passing through C,-C, and C,-C, and interchanging, H/H,, H1/H,, H,/H,, H/H,, 40,8 () Bisecting H,-CH, and H,-C, and reflecting H/H,, H/H, (b) Bisecting H,-C;, and HCH, and reflecting Hi /H, HL/H,,Stereochemistry (© Bisecting CC, and C.-C, bond length and reflecting HW, W/W, W/E, H/H,. (@ Bisecting C,-C, and C,-C, bond length and reflecting H/H,, H/H,, H/H, HH, (© Bisecting C,, C,, C, &C, and reflecting H /H, H/H,, H/H, and H/H,, Now, let us consider a case of substituted cyclobutane ~+ Plane of symmetry, -Achiral + Optically inactive, ci cle oO > Noplane ofsymmetry > Chiral > Optically active ci Me No plane of symmetry + Optically active cl a Plane of symmetry > Optically inactive COOH ~> Plane of symmetry ~> Optically inactive H cl cr 1. cea H + Plane ofsymmetry + Achiral > Optiacally inact 4 cl cr u By A H ow 4 —+Noplane of symmetry > Chiral + Optically active o + Plane ofsymmetry > Optically inactive + Achiral molecule, cl <1 of Bw > Plane of symmetry = Optically inactive Colts, COOH CHS “00H No plane of symmetry = Optically ative S Chiral molecule.Stereochemistry CH Hy HyC' CH 3c" “Hy COOH Hee ae Coon Plane of symmetry No plane of symmetry ~ Achiral molecule > Chiral motecule ~ Optically inactive. > Optically active Problem-2: Find out which molecules are/is optically active. os eo cf “ey ae 4 1 2 3 Br [%, BA “el Be Br Br Specification of configuration R/S : Then is absofute configuration of chiral centre Proposed byR.S. Chan, Sir Christopher Ingold, V, Prelog. Sequence rule: Priority to the four atoms or groups of atoms attached to the chiral centre can be deter- mined in accordance with sequence rule which are as follows. Rule 1: Ifthe four atoms attached to the chiral centre are al different, priority depends on atomic number, with the atom ofhigh atomic number getting higher priority. Rule 2: In case of isotope, the atom ofhigher mass number has the higher priority. For example among Br, C, D, H priority order is Br>C>D>H. 2 4 oe aha oe H—G—SogH H3C—C—Br 4 D3 Rule 3: [f the relative priority of two groups cannot be decided by rule mentioned above, then look for nextStereochemistry Rule 4: Where there isa double bond or triple bond, both atoms are considered to be duplicated or tripli cated. Ac I | —C—A 14 aac cH \ —c=cHy—> —C—C-C H If H (1) Assign the priority sequence by above mentioned method. (2) Find out position of the 4th group. 3) Connect 12-93 making a circle. : Hffourth group is below the plane, ‘LP. C LP Low priority group. C a HP — High priority group. HP. se y a LP. Clockwise + R Anticlockwise > S ‘Note: In this case 4th group'H' is below the plane and rotation is elockwise so, it is"R’ am 3 a CH, ey — HP. LP. HoH,c~\ %, 1 4 ‘Movement is clockwise So, itis R. Case 2: If fourth group is above the plane, rw BP. LP. Clockwise movement->$ Anticlockwise movement -> R. For example: 4 Zar oly . \Z Note: In this case 4th group is above the plane, c, So, clockwise movement gives 'S'. a” Case III: Ifthe fourth group is on the plane then do double interchange in such a way that the 4 group ‘undergoes below the plane.‘Stereochemistry For example: a 2 . js Qulchtacy In this case 4" group is on the plane. 1H” Yon, 3 Double interchange can be done as SOLVED PROBLEMS 2 cooH 1 4 1 : 3 CuwliMe i 2 (yn NH 2 fesdnooon neocX™,,, 1 2 Pw it s 3 OH “ s MY mm S-Methyl dopa I I 4 COOH 3 ICH,Br HO Br 2 i Note: In this case fourth group is onthe plane. So, we will have to do double interchange as shown below 3CHBr COOH CH,Br I Fint ' Second Comgoon PNA terchange™ AQ COM nergy HO! Br Ho "er 1. 20HL PROBLEMS Find R/S of the following compounds HAN, CoH ‘B/S Nomenclature in Fischer projection. ge Horizontal Line Nm eet eyee Intersection of these two lines represent C-atom. Vertical Line > away from the viewer. Horizontal Line ~> Towards the viewer, yea ‘Towards the viewer ‘Away from the viewer” For R/S nomenclature, Assign priority sequence, Case i If fourth group is present on the top or bottom of vertical line then t\ HP. LP, — Clockwise +R LP. HP. —» Anticlockwise > S1 NH 2 wos Loa Hye: COOH pe COOK aoe mae R NH H 1 4 CN a RR. Le. LP. AP. Clockwise > S Antclockvise +R For example: 2 3 oy, 3 chy Ph 1 200H 4 1 ‘NH; Cote H3C- ‘OH maw 7 ats 5 1 4 ; “ COOH 3CH, S OH CoHs $2 si 3 For example: 3 Ph ut 4 |s J 1 3 Hon Ho CH a z H3C’ Et H- Cos 4 Ss 4 Ss 3 CHO. Br 1 1 Conversion of Fisher -> Wedge. GHOH HOH. HOH;C. 40H CH Hac Cl HO—-H 5 fry a =) a, A ‘a Ona ltae “on fH ~0H ly Hy H L Bt” “ou Ho® ‘et Hs Ho por He cH, HOH Oe How" iy HOH H a y a Ho“, % oH “ou #0" Zo ts Note: Inall conversion, the configuration (R/S) should not be chang«CH He ph Hon on, H—--OH H Cols Cots, Conversion of fischer to sawhorse, FowW CH _ Ind carbon H OH ‘Note: Consider at first carbon shape like H: ‘OH (Pronounced 'Y') rah carbon H, (OH H. (OH oa eG Sts ; and then combine these two by a straight line like Hs oH Ht ‘ou oe H ‘OH Gis ‘Note: Since Fischer projection is represented in eclipsed form so the resulting sawhorse should also be in eclipsed formif we have need of staggered form we can obtain it by simple rotation. OTs For example: PL “Es Staggered form is suitable for elimination reaction since, for a form Ey elimination, the two departing group should be trans. H H Me, Me Me, ph s+ HOH + OTs wd Dd H Ph Tat Conversion of Fischer to Newmann: 2nd carbon, Me Ho, Reis Me an Ho, oes Ho. CoHs oh = — Staggered t—Catts eclipsed form — CHs oH form Me Me Me. Me Ist Carbon. | eclipsed formHOH Cate HO H (OH oleae #. H. OH — —> eal H ‘OH ¢, CoHs Hs ae Colts Eclipsed form 2nd carbon COOH poe) Holt oH 0. om HoH — —» MA ad wrLA,, Ist carbon. COOH carbon COOH st carbon CooH COOH ‘How we can apply these interconversion into reaction mechanism, Let us consider addition of Br, on cis-2-butene. cH, We + Bn —>? H ® Fs le H o Hy Ha, oe es A aa Ls wf Hee “e p/p HM cation Br Br By totation ep “aha H eH ‘So, Aand B are non superimposable mirror image to each other and hence They are enantiomers, Enantiomers: Enantiomers are the stereoisomés which are non superimposable mirror images to each other. So these two steroisomers have opposite descriptor. + Non super imposable mirror image. + Opposite descriptor ic. one is R and ather is S. 3 ame Fg wea | ou won | won Cts CHs “@ ®)Stereochemistry So, in compound “A’ and “B, the configuration at chiral centre are InA InB ici — / ETS GTR} So, these to ae enantiomer C3—R y—s Properties of enantiomer: 1. All physical properties such as M.P, reffactive index, vapour pressure, relative density, NM spo. trum, IR spectrum are same except direction of optical rotation. (Magnitude is same but direction is opposite). 2. Allthe chemical properties of enantiomers towards achiral reagent are always identical 3. Thechemicel properties of enantiomers willbe different inthe following condition Reagent | Solvent | Catalyst Result 1_| Chiral | Achiral | Achiral Difference in rate of reaction. i 2_| Achiral | Chiral] Achiral Difference in rate of reaction 3_| Achiral_| Achiral | Chiral Difference in rate ofreaction | Note: Ifwerun NMR spectrum of enantiomers in chiral solvent then it will be also different, 3, Whatis the relation between following compound, Az, syoOMe Aa g R some 0 oO So, these twa compounds are enantiomer, Diastereoisomer: Diastereomers arethe strereoisomers that arenot enantiomers. Some important points regarding the diastereoisomers. 1. Diastereomers can arise when structures have more than one stereogenic centre. 2. Themagnitude of optical rotation of diastereoisomers are always different but the direction may besame or opposite, 3. The physical properties of diastereomers are always different but difference may be more or less, 4, The chemical properties of diastereomers toward chiral as well as achital reagent is always different Examples of diastereoisomers: HOLL, rr ‘co,H Hoc bow Fumaric acid Maleic acid mp. 299-300°C mp. 140-14°C Note: geometrical isomers (ic. cis and trans isomers) are always diastereolsomers. A similar stereoisomers canexist in cyclic compounds, For example: 4-t-butyl cyclohexanol. oH 4 et MOH cis-isomer ‘Trans-isomer because-OH and tBu group mp. 081°C are projected in same direction ‘mp. 82-83°C ‘So, these two stereoisomers are called diastereomers. | LA| Storeochemistry Note: Diastereoisomers can be chiral or achiral. Moodle None oe) a See ‘Those to dastereoisomer: ae chiral because plane of symmetry snot present, ane of symmetry present 7” Plane of symmerry So, achiral diastereoisomers. NHMe ‘These two are diastereomers OH ‘OH Ephedrine Pseudoephedrine Remark: The diasteroisomers are different compounds with different names (For example ephedrine and pseudoephedrine) and different properties, while the pair of enantiomers are the same compound and differ only in the direction in which they rotate plane polarized light, {In summary ifwe haye compound having two chiral centre each one R/S then Re Ss os Enantiomer Gs] ‘Diasterovisomers 7 Baantiomer For example: OH | HOC. R i HOOC. 2 aon diasereisomes SPS coo | HO | enantiomers HO) enantiomers i QH oH i Hooc.s $ Hoc. s > COOH NES coon rt | iu diastereoisomers |= Zisstsreoisomers Meso Compounds: ‘Compounds that contain stereogenic centres but achira! are cailed meso compounds. This means that there is aplane of symmetry with R stereochemistry on one side and ‘S’ stereochemistry on the other. aS =Stereochemistry For example: t Plane of syenmetry Plane aCsymmmetry Mirror- : > Plane of symmetry Plane > SoMeso compound > Achiral > Optically inactive —>Mes0 Compound & Meso Compound Conversion of Newman into Fischer and relation between two compounds. 4 a Cl. Be H. CoH Cos ‘OH | Hse Br CH OH | @ | cl, Br HO. A a oH cl Br Since, in (B) CoH group is attached with back carbon and ‘we want to Bring itt fon carbon so we wil have to rotate itby 180, Hy Cals Gag CHS @ ® Br, | 1 4. 1H CHy ath Br Ch 3} — oh pes -d ‘oH, H——on n—ton CoH. * q ay ae CrHs (B) (a) Sa So, A and B are diastereomers. ee is the: sre between Aand B.| Stereochemistry Aa Ph s rl NH H Ht cl NH, Po @ ist “fs pag, CH CH So, these two are diastereomers GRE 1, Whats the relation between A and B. cl i city HOR, yBEH CH cl—— Br = — ed or HO—3—H OH ‘3 7) Cals CoHs @) @) CH a BH HO. ci — Br og SA and B ate identical He Gots , (A) What is relation between P and Q. NH COOH Ho. CH HO. CN Hoc’ NC NC NHp CN CHy | . NC, NC HO, oN HON, HN. OH 2 id CHy Clty COOH ‘COOH, CH Ho—S—cn HaN—}-—Ne CoonStereochemistry So, P and Q are diastereomer. CH 4H HOH HOCH 2. Br—t+H His CoHs Br ‘The molecules represented by the above two structures are (a) Identical (b)Enantioners (©)Diastereomers _() Epimer CHs HoH H poles prt by simple tation CoHs Cos So, these two compounds are identical. 3. The following two compounds are CHs GHy H—S}—on HoH aioe Ho—-H CoHs Hs (@Enantiomers -—(b)Diastereomers_(¢) Identical (@epimer. Soln. (a) 4, Which one ofthe folowing statement regarding the projetions shown below s tue? we, er Aub 3 represent the same ee (b) BothA.andB are optically active (©)Bis optically active. @Ais optically active a ct‘Stereochemistry “Avs optically inactive due to presence of plane of symmetry. (Correct answer is (a)) 5. Match List-l with List-I and select the correct answer using the code given below the lists. List List-H A. Meso compounds 1. Anequimolar mixture of enantiomer B.Enantiomers 2. Stereoisomers that are not mirror images C. Diastereoisomers 3. Non-superimposable mirror images D.Racemate 4. An optically inactive compound whose molecutes are achiral even though they contain chiral centre. A B Cc D @ 3 4 1 2 ® 3 4 2 1 © 4 3 21 2 Oe sea Son, @ 6. Whats the correct Fischer Projection formula for the compound represented by the following Newman Projection? CHOH HO. H Ho H CHO HO HOH CHO HOH HO: H Ho- H H ‘OH H -OH @ #4 ‘OH (®) HO: H ©to- H @u: ‘OH CH,OH CHO CHOH cHO CH,OH i Ho. H 4 — Soln. Ho" H Tuo ‘CH,OH Go CH20H Correct answer is (a) 7. Which one of the following Newmann projection formulae correctly represents a meso structure? Ph Ph Ph Ph H, on HO, Pho Ph on Ho. H ®, on Ow on Or on O oy H Ph # 4 Ph Sola.Stereochemistry Ph H. OH H’ ‘OH Ph 4. | OH HO. 4 Ph i Ph H—-0OH HOT—H Ph ‘e" has plane of symmetry so, it correctly represents a meso compound. CHO gH oH CH.OH Which isthe correct order of priority of groups attached to the chiral carbon n the compound givenabove while as assigningR or ‘S" configuration. (a) HO > CHO > CH,OH> H (b) H> CH,OH> CHO> OH (©) CHO > OF > CHLOH > H (d) CH,OH> CHO> OH>H Soin. (@) 9. Which one is the correct configurational assignment (in terms of CIP principle) for each ofthe compound listed below? 2 a 3 ee ClH0, COOH 1 4 N=” HoN CH Po\ 7 HgCH,C 9, aH Ph 0 I @ER ILS (FS, I (LL, WS (ES,UZ Soln. (@) 10. Consider the following configuration of 2, 3-dibromobutane. 8 Hy a ee _T eH @ a @., H CHs (3) HBr 4 ir CHs Which one of the following is the correct answer?Stereochemistry (@) Conformation (1)is the meso-form while (2) and (3) are an enantiomeric pair. (b) Conformation (2) is the meso-form while (1) and (3) arean enantiomeric pair. (©) Conformation (3)is the meso form while (1) and (2) are an enantiomeric pair. (@) Conformation (1) and (2) are identical and (3) is the meso-form. Soin. CH3 Br CH. Bx Ms HL ot Bx ° H ‘sr |" ‘CH 1 pr H Br CH; Yen on Y HB : Ho oer Bho ey oat chs ay Guy | CHs bal Y By CH3 CHs aH nS} er Haier Brg CH, CH: Cc Is a) ig Hs wt 4 (3) having plane of symmetry So, these two compounds are enantiomers So, itis a meso compound. So, the correct statement is conformation (3) is the meso while (1) and (2) are an enantiomeric pair 11. Consider the following statements regarding the given projections. CH,OH CH OH CHOH CHOH y ‘Br HO- H Br- H HO. H HO: ‘H H ‘OH HO- H HO” H CHs CHs CHs CHy ) @) © ©) @)(A) and (C) are diastereoisomers. (2) (D) is the Newman projectoin of (B).. (3) (B) may be named as thereo-1, 2, 3-butanetriol. Which of the above statements are correct? (@)1,2&3 (b) 1&2 ©)2&3 (a) 1&3. | Hon HoH cH.o# | nl 7 HO- H Br- +H | s g | Soln. 4 ¥ ‘OH Ho- 1 | | oH Gtig oH ; @ ® © | GH,OH Hot) Pa CH.OH Lacs a H—)—0H bw Ye we | Gi0H | Chis CH CH ©)— co | So, Aand C— are diastereomers. Disnot the Newman projection ofB. HO, a HoH ‘The Newmana projectionof“B’ is ‘CHZOH CH3 Soin, @. Epimers Epimers ore the diastereomers, differ in the stereochemistry at only one stereacentre, ‘The term can be applied only to the chiral compound having morethan two chiral center. For exemple glucose and glactose have difference in configuration at G, 80 they are epimers at C,. 1 cho ‘HO Ro 2H-—}—on Rows S 3Ho—+—H R s5H—}—on 6 CH,OH CH.OH Glucose Glactose Similarly glucose and mannose have change in configuration.at C, so they are epimers at C,. 5 GyoH HOH Glucose Mannose " “ ® on Compouna (A) and (B) ase epimetic pair, Anomers: Anomers are the diastereomers (in the case ofa monosaccharide) which differ in the configuration atC, are called anomers.Stercochemistry o-anomer o-D-glucose D-glucose GT TES Soin. Identify the correct sct of stereochemical relationship amongst the following monosaccharides I-IV. ro oH ‘ome — 9'Y¥ 9 ome val OH on nm wot @L andre anomers; IIT and TVareepimers. __(b) Land Il are epimer; Il and IV are anomers. (c)Iand are epimers; HandIV are anomers. (4) Land IIT are anomers; 1 and If are epimers, @. ‘Threo and Erythro nomenclature Threo and Erythro nomenclature are based on sugar chemistry. CHO same CHO ye fifferent Ht Ho H CHOW CHOH DE erythrose DO) threose + Exythrose and threose are diastereomers. + Amolecule with two adjacent stereocentres, when there are two groups which are commonto each carbon while thirds different ie. C,,C,, gives ise to erythro and threo diastereomer. Procedure for finding erythro and thréo diastereomers. Step I: Find out the group or atom which is not common on two adjacent asymmetric centre, ‘Step Il: Placed this different group on top and bottom position of vertical line in Fischer projection formula. Step III: And arrange the rest group or atoms around horizontal position of Fischer projection. Case I: Iftwo similar group are on the same side then it is called erythro. ‘Case IT: Iftwo similar group on the opposite side then itis called threo.— | om | Son. Solu. (b) Hint-Condition for erythro and threo are C.-C. For example: f oHictty toe ‘These two are different group on the two H—t-+e asymmetric carbon placed at top and bottom. CHs ‘These two H, atoms are projected in same side sa, it is erythro CH,CHy a) @4-* CH In this structure the two similar group viz Hand Br are opposite so, itis threo. ‘Nate: The terms erythro and threo are generally applied only to those molecules which do not have symmetric ends. Im summary, condition for erythro and threo nomenclature: (1) Two asymmetric carbon should be there @ Ontwo asymmetric carbon, twa of the groups are the same and the third is different, Consider the following statements about the Fischer projection A-~D, COOH Hy CH CHs HO: ee OH Ht Br HO: 4 Ho: HBr 4. 8H Br Hy CHs CH CH (A) @) © () (1) Aand Bare erythro forms while Cand D are threo forms. (2) There must be two assymetric carbon (3) Cisameso form while B and D are dL form. (4) Aad B ace meso-form while C and D are diastereomers which of the above statements are correct? (@) 1, 2and4 (0)2,3and4 ©3 (@)2 and 4 © ‘Which ofthe following compounds ar threo and erythro isomers? w a @ ae @ Ae eth, (a) &2 1&3 1&4 (284Stereochemistry 4. Soln. Soln. ‘Consider the following statements. In the elimination reaction, CRs Ph, CHy Base = Ng Ph—CH—CH—Ph ——» C=C, i =a’ py Br (1) Ofte various stereoisomers of the reactant, only stereoisomers of proper geomet, that is conformation will undergo this elimination reaction. (2) Exythro isomer will undergo elimination reaction at a faster rate. (3) The threo isomer will form the trans olefin ofthese statements. (a) 1,2 & 3 are cotrect (b) 2 &3 are comrect (©) 1&3 are correct (@ 1 &2 are correct, Br Sr H——Ph utr Ph——HH “_ bs . Threo Isom erythro isomer Le | a y HO Ph Ph Ph, HO Ph I Br CH3 oe Br Br 0" J Ph use tery Ph, H Rate of elimination will not be faster Noa’ + ‘because the two bulky Ph group projected a ra \, in the same direction causes steri chindrance i Lid and will increase the activation energy ofthis trans product conformation. Correct answers (c) Find out the stereoisomers of 3-bromo-2-butanol 3-bromo-2-butanol have two asymmetric centre. So, the total number of stereoisomers = ‘These are CHa CHy CH CH i OH HO: H ‘OH Ho H H Br Br H Br H # Br CH CHy Exyiiro enantiomers= ea r (A) Optically activity in-biphenyls \ ‘Two conditions are necessary for biphenyl compounds to exhibit optical activity, i) Neither ring have a vertical plane of symmetry, i) The substituents in ortho position must have a large size. Note: There is no chiral centre in Biphenyl, it is the molecule as a whole which is chiral, duce vestricted rotation. The chirality due to restricted rotation arround C-C single bond in biphenyls known as atropisomers. Remark: If Hl, Fand-OCH, group are present on ortho position of bipheny| then rotation ofthe ring willnot be prevent, Because the volume of these groups are too small to prevent the rotation about the single bond, cl 4 Me OO | O oC Hoag" NO2 cl ch 7 ON. ° COOH ON. O COOH OC NO, er —r Properly sobatinted ~ Property substituted + Propedly subetated ~+ Restricted rotation > Restricted rotation easiest +0 optically ative > So optically active So optically active a Hoe. H3c ‘CH cr 'NH2 O cu a Hc. CHs om O Properly substituted > Not properly substituted i Not restricted ro! ee —Achira (restricted station ~> So apically inactive Optically inactive >But not properly substituted) > Optically inactive Hs 1Bu 4 . 'SO3H Bu ! Optically active Optically active ‘Bu is bulky i inStereachemistry Some more examples of biphenyl fype compounds are as follows: HoOOG HQ, Hooc, cts Hoon fs A a sS nf NN, 0 — a) a SS, @ COOH CH; CHa HC coon COOK O COOH N COOH COOH CO 000” ‘COOH HsC. NOp 7 Properly substituted but ® not ristrcted rotation So, O opsicaly inactive, H3C° COOH cl HOOC~ 2°Y7 1 ~NOp Put the head ofthe arrow on which side 3% ‘where configuration ofthe ring is defined in Hooc. 'H3 the problem and thea assign priority sequence asper CP rule ‘Br Sisomer © BUS in Biphenyl:Sirectenists Q Hooc™ 27 ~Noz, ONa Se 4 COOH S-Form Me Me a7 er On? 1 “coon 4 3 CH, On. 4-COOH $0 is S-tsbmer R S-Isomer (B) Chirality in Aenes Alllenes are chiral due to chiral axis. Essential criteria for chirality of allenc. (1) Propersubstitation (2) Number of double bond should be even. Properly substituted means that terminal carbon ofallene should have two different groups, So thatit deprive from plane ofsymmetry. 9 sp? Y (ir / 7 \ H 4 sp“ symmetry element 308 ov Problem-1: cl cl Nay a frorg @ H H cl > Nurser of double bond even ~> Number of double bond = even = Propecly substituted ~ Properly substituted. ~ Soitis chiral ~ Soitis chiral a‘Stereochemistry Br, H \ d OF aaa. or F > Number of double bond = ever > Number of double bond = odd ~ Properly substituted <> Properly substituted So, itis chica. > Achiral, optically inactive. Ph, \ © \. ef ‘coocH,COoH > Number of double bond = even — Properly substituted + Chiral, optically active Note: One of the double bond ofallene may be replaced by a four, five & six membered ring and the general shape of te allene molecule isretained, For sucha system. Optically activity arises if Number of doubled bond +ring =even and criteria for properly substitution is same. > “ \ ‘OH + 1 double bond ++ one ring=2= > Properly substituted > Chiral and hence optically active, H Br, \ 7 Xn @ wa Nom chiral a \/ + Number of double bond = even, ~ Property substituted > Chiral, Optically active Problem-2: 1 double bond + 1 ring even — Properly substituted > Chiat, optically active. Problem-3: Br, CH \=e / HN chiral centre CH; +2 double bond +I ring = odd > Properly substituted tis chiral, due to chiral centre but not chiral axis. > 2 double bond + 1 ring= odd + Property substituted > Achiral, optically inactive,Sereachemisry RSin allen. 2 1 _ ‘ 3 4 Hoog H Mesc, Me \ Z \ tt \ \y - Q) / ha o (2 “4 rt %, % O° af ~ @ me “al yf i R Reform S¥om (©) Optical Activity in Spirane: + Ifboth double bonds in allene are replaced by ring system, the resulting molecules are spiranes. ‘Examinations of these formulae show that the two rings are perpendicular to each other, and hence suitable substitution will produce molecules with no element ofsymmetry, thereby giving rise to optically ative formas. Essential criteria for chirality due to chiral axis, 1, - Even number of ring in spiro compound (Odd number of iro carbon) 2. Proper substitution at only terminal H. Spirane has two types of hydrogen (i) Lateral (2) Terminal. ‘Tenminal hydrogen 4HT’s are terminal, 8H1’s ate lateral, + Chirality due to chiral centre can be generated in any spirane compound (even of odd number ofring) by substitution at lateral hydrogen (Plane of symmetry should not be there), + Chirality due to chiral axis can be generated in spiranes having even numbers ofrings by propet substitution, H, H -) ‘Terminal hydrogen Lateral hydrogen chiral > Number ofrings = even ~+ Number of ings = odd > Properly substituted. > Not properly substituted ~+Chieal due to chiral axis, ~> But chiral duet chiral centre not due to axis. iSSteteochemistry 4, H YOK HN NH > Number ofrings = even > Properly substituted Chiral, ue tochiral axis, Le nomenclature in spirane toallene and a ; H2 NH, Sook. Rilsomer DOCK trom “MM HAN’ “ Planar Chirality: + Specific type ofchiratity known as planar chirality. * Chirality can not be removed it is permanent. View te molecule fiom op Fe "PPh ‘pS—> This * sten for pianar. Ps Note: NMep of \ Me Fe O ‘The side chain has a chiral centre such type of chirality is called lateral chirality. Conformational Analysis Conformation studies of unsaturated compounds and compounds containing the oxo group have ed to some ‘unexpected results. For example, microwave spectroscopy has shown thatthe preferred conformation of propene and acetaldichyde are the eclipsed forms and NMR spectroscopy has shown that the predominant conformation of propionaldehyde isthe one in which methyl group and oxygen atom are eclipsed. The reason for these observation is uncertain. ISStereochemistry i HyC—G=CH T HyC—CHy>—C—H HsC—C—H Propionaldehyde a 4 SH, CH, 7 <0 H H H H i e WS H ise meee Propionaldehyde ‘Remark: Molecule suchas ethylene chlorohydrin or ethylene glycol, intramolecular hydrogen bonding is possible in the skew form but not inthe staggered form, due to this intramolecular H-bonding the molecule is, stabilised by about 20-29 ki/mol and thisis enough to make the skew form more stable than the staggered form. Evidences-LR. spectroscopy has shown that the skew form predominates. H 7 escicsng o H On, H H H H H H Gauche form of ethylene diot Gauche form of ethylene chlorobydrine Method used to investigate the conformation of molecules. + Thermodynamic calculation + Dipole moment, + X-ray and electron difftaction +IRand UV spectroscopy + Chemical method, + NMR spectroscopy Conformational Analysis of Cyclohexane Factor affecting the stability of conformations (1) Angle strain: Any deviation from normal bond angle (2) Torsional strain: Any deviation from the staggered arrangement, G) Vander waals steain(Sterie Strain): Any two atoms (or group) that are not bonded to each other can interact in several ways depending on (@) Their size (b)Polarity (©) How closely they are brought together. ‘These non bonded interaction canbe either repulsive ot attractive, and the result can be either destabilization or stabilization of the conformation. \ Bayer suggested (incorrectly) there should be certain amount of strain in cyclohexane, ‘Two most stable form of cyclohexaneare as follows: | a WY | Chai foe, ‘Boat form | Chair form is more stable than that of boat form due to following fact. €Stereochemistry Chairform Boat form Q) No angle strain (1) Noangle strain Q) No torsional strain (2) Torsional strain i present. 3) No flagpole interaction (3) Flagpole interaction is present (vander waal strain) (A) No any eclipsed etfiane condition (4) Two eclipsed ethane condition (will creat torsional strain) Conclusion: The boat conformation is less stable than the chair conformation, (<——— Flagpole bond boat conformation in Newmann projection formula Potential energy relationship among conformation of cyclohexane. Stability order: Chair> twist boat> boat > half chair Mono substituted cyclohexane: LT Equatorial aa More stable No, interaction Les stable duc to 1 interaction Half Twist oat chair boat Remark: Except for ‘H’, a given atom or group has more room in an equatorial positions than the axial position. Most molecule (about 99% at room teraperature) exist in the conformation with methyl in uncrowded equatorial position. Disubstituted cyclohexane: 1, 2-disubstituted cyclohexene Homo disubstiuted Hetero disubstiatad cyclohexane. Cis and trans relationship in disubstituted cyclohexane can be understood as 1, 2-disubstituted cyclohexane, 1,4-disubstituted cyclohexane, 1, 3-disubstituted cyclohexane. Cis —(a, €) or (¢, a) Cis — (a, e) or(e, a) Cis — (a, a) or (¢, e) ‘Trans — (a, ) orc, €) Trans — (a, a) or(¢, €) Trans —(a, €) or (e, €) Let us consider an example of 1, 2-disubstituted cyclohexane, CH, LY CHs) Trans] Dw CH (CHa CHs CH OC aae Me) Mee > iS‘Stereochemistry [ T& Tare degenerate because both have one 1, 3-interaction. II & IV arenon degenerate | Lis east stable because inthis case both methyl group is placed at axial position and suffer 1, 3-interaction, So, the stability oder is TV >1> I> IIL i 1, 2-disubstituted cyclohexanes with two different substituents. Let us consider an example of I-ethyl-2-methyl cyclohexane. Zs. Lt ore cy (D@e) (2) as a) GB) e (4) js 5 1 and 2 arenon degenerate. Remark: Energy of conformation (2) will greater than that of (1) because, the bulky ethyl group is at axial position which suffer more 1,3 interaction. Me 3 and 4 are also non degenerate, out of these two conformations, (4) has maximum energy because both, methyl and ethyl are placed at axial position where they suffer severe 1, 3-interaction. So, overall stability orderis3 > 1>2>4. Optical activity: Hy | Ss : “L—7 Api ofnantoner HgC : CH: 1, 3-disubstituted cyclohexanes (1, 3-dimethyl cyclohexane) Cis-), 3-imethyleyclohexane, ‘Trans-1,3-dimethyl cyclohexane. wes ne ee Me @Ga Mee Hs 3 and are degenerate. Land 2 are non degenerate. Energy order 1 >3~4>2. Stability order2>3~4> 1 Note? In Cis-1, 3-dimethyl cyclohexane, plane of symmetry s present in both (a, a) or (e, ¢) conformation.Stereochemistry “> Plane of symmetry LET m LDu @a) However, trans 1, 3-dimethyl cyclohexane, does not have a plane of symmetry and exist as a pair of enanti- omers. Let us consider the case of I-isopropyl-3-methyl cyclohexane. cis-1-isopropyl-3-methyl cyclohexane. trans-isoprophyl-3-methyl cyclohexane. L~/ we LJ pL bie LY Me Pr Me 1 () @a) @y(e.2) G3) @e) @(ea Mr J and 2 are nondegenerate. 3 and 4 are non degenerate. Stability order: 2>3>4>1 L___, Both group at axial postion = > Bulkier group (-Pr) at axial position Both group at equitorial postion Let us consider an example of 1,3-ditydroxy cyclohexane. Cis-1,3-dihydroxy cyclohexane. trans-1, -dihytroxyeyelohexane. l~Y{ HO. wo fT, on -—Lo LT OH Cal ()@a) eee) Ha@e ea OH Stability order 1>2>3~4 Conformer (1) is more stable than that of (2) because of the fact that in case of (1) intramolecular H-bonding ispossible. pStereochemistry Lato 1. Fromwhich conformation of cis-1, 3-cyclohexane dicarboxylic acid anhydride will be form. ee COOH Ring flip <00H ic) Soln, Cis-cyclohexane-1, 3-dicarboxylic ‘A| Cis-cyclohexane 1, 3-dicarboxylic acid acid diequatorial conformer diaxial conformer(Less stable) (More stable) Anhydride Remark: The-COOH grop in(A) are farapart for anhydride formation. Ring flip to give (S) ‘rings them with, inreacting distance. 2. Draw the favoured conformation of following compounds OH On Me, QOH < Sola, (1) Oo “er favour ‘Two substitueats OH equatorial (aon-axial) No substituents equatorial ‘wo (axial) Ch LL ey TA Since Br> OH (in size) HO Br favoured cu) “oy iPr wr OH w) be m7 Favoured on Two sbstitentsequoral one axial, One substituent equatorial vo axial iqStereohemity 1, 4-disubstituted cyclohexane: Let us consider an example f 1, 4-dimethyl cyclohexane. Cis-1, 4-dimethyicyclohexane. trans-1, 4-dimethylcyclohexane. Me Me aw) ~~ "we LT we (1) a) Me (2) (a,e) @B)@e) Me (4)(@,a) Stability order: 1>1~ 2>4. Soe 1, Draw the most stable conformation ofcis-1, 4-di t-butylcyelohexane. a Bu Remark: An axiai t-butyl group is very unfavourable form. In Cis-1,4-di-t-butyl cyclohexane, one t-butyl ‘group would be forced axial ifthe compound existed in a chair conformation, to avoid this, the compound prefers to pucker into a twist boat so that the two large groups can both be in equatorial positions (or Pseudoequatorial, since this is not a chair). 2. Draw the most stable configuration of et oe: Me , ron Bu “oH CHs Me ‘OH Remark: The bulky t-butyl group is particularly prone to occupy an equatorial position ifother substituents are considerably smaller than t-butyl, the molecule is virtually locked ina single conformation. The one withan equatorial t-butyl group. t-butyl group has been widely used as a holding group to permit the study of physical and chemical properties associated with a purely axial or purely equatorial substituent, 3. Themoststable conformation ofthe following compound i: Me Me tBu ie ov Te on LZ, Me on LF oml——ym Me Me‘Stereochemistry & [ | | He Ans. LI . Because t-butyl group is locking group. Me 4. The favoured vicinal diols shown below only three are cleaved by HIO,, The diol which is not cleaved HIO, is: oH vol \ tBu! “OH t-Bu “OH . oH oH 7 LO 7 sen cau ro vou on | OH OH ‘OH tBu tBu ‘on tBu on tBu, on Soln. OH @ © @ (@) Because in this case the two-OH groups are diaxial, so there is mote distance between two OH groupsand hence will not interact with HIO, effectively. 5. Accouts for the fact that only one of the following compounds A and B give the expected elimination product with KL acetone, ey Me to” Br @) ®) Br tBu wo Ls Soln, Br {A) Br @) (A) will give the expected elimination product with KI in acetone because for B2-elimination. The two depart ing group should be placed at diaxial position (or antiperiplanar) such requirement is only flfilled by compound a). 6." Which of the followingis a cis-isomer? Me chs © L—Tm © re LT al a ‘Me CH Soln, (¢) Because in case of 1, 3-disubstituted cyclohexane cis means (e, €) or (a, a). aqStereochemistry Soln, Soln. Soln. ‘The stable form of trans-1,4-dimethyl-cyclohexane is represented as Hy Hs @ “7 © os use. mc 7 on @ Os (©) because both groups are at equatorial position, Identify the hydroxyeyclohexane carboxylic acid, which upon heating readily gives abicyelic lactone Lyre o LTDoe © CHs OH © L~ OH | HO—H | CHs 46H, CH; | Rulacticacid ' Sclactic acid Homotopic ligands and Faces: + Ifthe substitution of each one of them by another atom or group leads to the same structure. i H3C—C—OH Joon all 3H are identiais, so homotopic in nature we Hoy os Homotopic face: Ha CH‘Stereochemistry ° i KAY Hy marae aan) % homotopic face homotopic face Enantiotopic ligand and faces 1 “Epon 2 +H R Hy 0H COOH (25,32) ‘These two are not non super imposable mirror images to each other but still diastereoiomers. Hy, pon Hy, pH Hy and Hi are reflected by a plane COOH So these two are enantiomers to each other. CooH > HF ate homotropie becaue itis “GH, interchanged with C-symmetry. HOHC'IN 9, ——> enanotonic ——— Hy/ity, ~ are enantiotopic Diastereotopic ligands and faces:Stereochemistry HYCL—-H3C, Cl TH — ScmecZ So these two are diasteroismers FON, H cis(2) ‘rans (E) HyC, H No” be — H Ho (WO HO HO. Hyon te nyo Ha — — H H H Hy Hy OH trans So, H, and Hy diastereoisomers Hs Hci wtia Ha, gi 4H, CHs a a cH, 2 CH HEN. CN OH HO: CN Hy¢- Ho ES HyC: H HyC: H CoH CeHs CoHs Methyl o-phenethyl ketone ° a OH in Lf — wou LJ * on L~7™ 4 tans os ‘So this face is diasterotopic aert Oey Me Hy chty So Hye daeeisomers because it s “m P 4 Hore 2 2 @ WR 7 ‘OH H3C . 1 oy 2( 9 2 a 7 Hat CH 3 HyC’ ‘CH2CH Se-face Resface Re-face CHy diastereotopic since there is no syrametry and the two methyl group are close {0 a stereogenic centre 3 aH, HsC~~CHs * diastereotopic when the rotation of the ring is slow when rotation becomes fast these protons become enantiotopic (average mirvarplane) 4. Indicate H, and H, are homotopic, enantiotopic or diastereotopic. Ha Ha Hi ° 2 Ma Ho, gla He y fi WoC eat Q diastereotopic| replacement test Hy homotopic would give «yn and anti compounds enantiotopic homotopic Ke)@ () Soin. Stereochemistry Let us consider an example of norborane system first we want to discuss the symmetry properties ofthis system, Hs Hs Ithas one C, axis passing through C, and interchanging C/C,,C/C, C/C, H/H,,H,/H,,, H/H, H/H,, HB, HY/H,. So, these protons are identical (as we know the protons which are interchanging with an axis are identical ie. homotopic protons). Now, Ithas two, 9,,-bisecting C,-C,-C,, H,,, H,, reflecting C/C,, C/Cy HH, H/H, H/H, H/H, H/A, 6, bisecting C,, H,, H, and reflecting C/C,, C/C,, C/Cy Hy/H,y HY/H,, H/H, H,/H, H, /H,. ‘The protons which are reflected with plane are enantiotopic where as those which are bisected with plane are diasterotopic. Note: Ifa protons are interchanging with C, axis and also reflected by plane the priority will be given to interhanging by axis and hence it will be homotopic but not enantiotopic. For example Ha He HH, are interchangabe with C,-axis and also reflected by a plane. So, in this case priority will be given to former not later and hence H,/H, are homotopic proton. Identify the correct stereochemical relationship amongst the hydrogen atoms H,,H, and H. in the following molecule, [GATE-2006] He i He (@) H, and Henantiotopic (b)H, and H, : diastereotopic (©) Hand H:; enantiotopic (O) 8, and H, :diastereotopic Since, HJ, ane Hf, do not have direct relationship with any symmetry element. So, we will have to see chemical environment around H, and H, since the chemical environment is different viz H, is exo where as H, isendo so these protons are diastereotopic. HH, are reflected with plane hence itil be enantiotopic, HH, diastereotopic Correct answer's (b) GqSserochemistry 6. The two H’s at C-2 and C-3 in (2R, 3S) tartaric acid. (@)enantiotopic -—(B)diastereotopic (homotopic (@ constitutionally heterotopic COOK H— COOH Soln. These two hydrogenes are reflected by a plane, So, itis enantiotopic. a ca 1 Ait, a The relation between H/H are (a) Homotopic (b)Diastereotopic _(c) enantiotopic CSIR-IRF-2008 Soln, Since H, and H, ae interchangable with C,-axis so these two are hometopie. 8. Consider the hydrogen atoms labelled as Hi, and H, in the following molecules. [IAS-2008 ] COOH Chg Br HG, Ha a Hy—}-— 0H 5 H—}—0H ms R qa) POOR Hp) OH Hy He (4) H ie cooH CHs He R Inwhich of the above are H, and H, diastereotopic (a) 1,2.and3 (b) 3,3 and'4 ()1,3.and4 (@)1,2and4 Soln. (b) have plane of symmetry so li, and H, are enantiotopic in the case of (3). H, and H, are adjacent to the chiral centre so these two protons are diastereotopic while in case of (4) no direct relationship with symmetry clement while chemical environment of these two protons are different so these two are diasterotopic. So, the correct answer is (c) 9. Consider the following molecule S: BAS.2007) 1 trans-1, 2-dichlorocyclo propane, 2. cis-1, -dichlorocyclo propane 3.1, 1, 2-trichlorocyclopropane. In which of the above molecules is/are the sets(s) of methylene hydrogen(s) diasterotopic? @ Jon o 1 a (@)2only Incase a the reer H’sareexchangable a symmetry so, these two are homotopic while in (2) ‘methylene protons are bisected with a plane so these two are diastereotopic In caseof (3) No methylene protons are present. So, correct answer is(d),[ Sereochemistry 10. Consider the following compounds. He Haz, pit Hy | Hho-e—e—chis Bro Hy Hy I 1 Or Identify H, and H, hydrogens in the above compounds. (@)diasteréotopic, enantiotopic, homotopic respectively. (b) Enantiotopic, diastereotopic, homotopic respectivel (c) Homotopic, diastereotopic, diastereotopic respectively. (@ diastereotopic, enantiotopic, diastereotopic respectively. Soln. (a) no (IAS -2006] H ‘Cy ‘What are the two methylene protons in the above compound called? (a) Homotopic protons (6) Tautomeric protons (©) Diastereotopic protons (@ Enantiotopic protons. Ans. (6) Ha, x oO ‘Oo 12. WE Hy He “He Consider the following statements conceming the features of the protons of the structure given above 1.H, and, are homotopic 3.H, and H, are diastereotopic 2.11, and Hy, are enantiotopic 4, Hand HY are vicinal and cis. Which of these statements are correct? (a) Vand2 (b)2and4 (©1,2and4 (@2,3and4 [148-2003] Soln, H,, and H, are homotopic because they are exchanged with C,-axis. ‘Hand H, are enantiotopic because they are reflected with a plane. H, and H, are not diastereotopic because they reflected with a plane but not bisected. So, the comect answer is(c). 13, Inthe compound (HAS-2001] Hs 7 cl Ww a ‘The two hydrogen atomsmacked as the H, and H, are (a) enantiotopic (b) diastereotopie ()homotopic @ anomer. Soln. (b) because these two methylene protons are adjacent with chiral centre,CHAPTER Reaction Intermediates 41 Reactive intermediates are believed to be transient intermediates in majority of reactions. The main types of reactive intermediates of interest to organic chemists are carbocations, carbanions, radicals, radicalions, carbenes, nitrenes, arynes etc. Reactive intermediates are usually short lived, very reactive and very seldom isolated under normat reaction conditions, However, their structures are established either by means of chemical trapping or spectroscopically or sometimes by isolating themat very low temperature, The shapes of these intermediates ‘become important when considering the stereochemistry of reactions in which they play a role, Carbocation Carbocation has a positively.charged carbon atom which has only six electrons in its outer valence shell (A) Structure and stability of carbocations: The heterolytic fission of a C-X bond in an organic molecule (X is more electronegative than carbonatom) generates the negatively charged anions (X:) and positively charged species known as carbocations H rr I Heterolytic I ney ee we or fi H Carbocation ‘The carbon atom in atypical carbocation isp? hybridized. The p,, orbital is empty and is perpendicular to the plane of the other three bonds. Thus carbocation adopts a trigonal planar shape. a Binoy prorbital R Qo "C—R 5 “ F120 Side View rope Casbocation Planar structure of carbocation is more stable than pyramidal structure this has been shown by quantum mechanical calculations and confirmed by NMR and IR spectroscopy. That is why formation of carbocation is, prohibited at bridge head position due to formation of nonplanar carbocation. ‘Ned-Amnet! measured directly carbocation stability by measuring the enthalpy of reaction for the ionizationof RX process in SbF/FSO,1/SO,CIF at -40°C, Rx ——» + xRea ion Intermed ‘The stability of the carbocation increases when electron donating groups are present. ‘The reason for the order ofalky| carbocation stability was simply as inductive stabilization of the positively charged carbon by its attached electron-releasing alkyl substituents and by hyperconjugation (“no-bond resonance”). This explains why a tertiary carbocation is more stable than a secondary carbocation which in turn is more stabie than a primary carbocation. HCNO CH Hee 4 Hoe -H H@ LH C c | a Le ee | CHy CHs H H PS P methyl However, the presence of electron attracting groups (like nitro, carbonyletc.) adjacent to the carbon atom bearing positive charge makes the carbocation less stable, Resonance effects can further stabilize carbocations. By resonance the positive charge on the central carbon atom gets dispersed over other carbon atoms and this renders stability to the carbocation. The more the canonical structures for a carbocation, the more stability will be. Q ® CH CH, Ch CH CH, © @ —_— — <—_— <—— é Benzyl carbocation Anallylic carbocation has two resonance structure. © ® wear, > noon, The order of stability ofthe benzyl, allyl and iso-propyl carbocations is: CHs @ @ I CgHs——CH, > HC==CH—CH, > Hoe— GH In certain cases, the carbocations are so stable that their solid salts have been isolated. For example the tropylium bromide is stabilized by aromatization. The tropylium cation is planar and has 6 p electrons like benzene, Triphenylmethy! perchlorate {real crystalline solid) ‘The order of stability of tropylum, riphenymethyl, benzyl and allyl carbocations i: @ @ a) Tropylium cation > (CelHs)sC > CgHgCH, > = H2C=CH-CHp Tripheny| methyl Allyl carbocation ‘carbocation ‘The carbocation stability order of alkyl (1°, 2° & 3°), allyland benzyt'carbocations. @ CHP < crycH? < (CHypcH? = Hac=CH-BH, < caHeCHE < (CHa?‘Reaction Intermediates The carbocation stability isalso increased due to the presence of heteroatom having an washared pair of electrons, e.g. oxygen, nitrogen or halogen, adjacent to the cationic center. Such carbocations arestabilized by resonance, The methoxymethyl cation is obtained as a stable solid, MeOCH,'SbF. The stability of the cyclopropyl carbocation increases with each additional cyclapropy! group. Y D-€ < DErd< Di (B) Generation of carbocation: (1) From alcohols : Alcohols on treatment with concentrated acids get protonated and then may lose a molecule of water to form carbocations ® -H,0 Roon + HO —> ROH, Pe R? (2) From alkyl halides: Jonization of alkythalides give carbocations. Rox Solve, p94 x (Ke B.C ‘The process is accelerated by the presence of powerfull ion-solvating medium, metal ions such as, Ag* ions or Lewis acid. In place of alkyl halides, alkyl tosylates and alkyl mesylates can also be used. Friedel-Crafts alkylation ofaromatic compounds involves the formation ofa carbocation that acts as¢lectrophile. Be @ RX + Aly == |R-X-AIC | —— R + [ x-aict, @) From alkenes: Addition of proton to alkenes or other unsaturated species give carbocations. AA +§— & "CH, Hac ‘CHy ls Qe @ Br (CHY,C=CHy + HHBr ——~ (CH3),C—CHH ——> (CH)sCBr ‘3° Carbocation t-butyl bromide: (4) From diazonium ions: ‘The alkyl diazonium ions are unstable and decompose at room temperature to give carbocations. 2. ® RONEN» R® + Ny (5) From acyl halides: The acyl halides on treatment with anhydrous aluminium chloride gives a complex, which decomposes to give acyl carbocations. Inmost Friedel-Crafts acylation, the electrophile appears to be anacyliumion. R~cocl + AIC @ e Rcoct-Alcl | ==|(R-C An acylium ion isReaction Intermediates 2. (© Reactions of carbocation: Carbocation usually undergoes elimination reactions, addition reactions, reactions with nucleophiles and Tearrangements. Elimination of a proton: A carbocation may loose a proton to form an alkene, For example, I-propyl carbocation generated from diazonium salt may eliminate a hydrogen ion to form an alkene (propene). Alternatively, 1-propyl carbocation may rearrange to more stable secondary carbocation, which may also loose a proton to give propene, ‘NaNO; @® 9 CH,CH,CH,NH, a HgCH,CH,C.NENCI Propyl amine Propyldiazonium sat . | A ® 128° oH,cH,eH, ——> Hicho=cH, CH,CHCH ~~ -H,CH;CH, an 2 m 1° Carbocation Propene 2° Carbocation Reaction with nucleophile: Accarbocation may combine with a nucleophile to form anew bond. @ 2 CHs-CH=cH, + He! ©", Hgc-CH-cH, + Gl cl @ © _ fast HgC—CH—CH, + :¢]: —~—» HxC—CH—CH, 2° Propyl carbocation Isopropyl chloride ‘The reaction of carbocation with a neutral nucleophile such as water gives a protonated alcohol, For example, Tertiary butyl carbocation reacts with water (neutral nucleophile) to give protonated t-butyl alcohol, which climinates a protonto give ¢-butylaleohol, gow CHs —H > H30—C—~O <> 0—C—0F H CHs CH Teatiary butyl Water Protonated t-butyl alcohol carbocation (petal ucloptfe) "buy alebol Reaction with alkenes and aromatic systems: A.carbocationmay react with an alkene to produce another carbocation. CH, CH, CHy is CH if al | I ete — Hao —G— ClCH HyC—CSCHy + CH 2-Methyl propene — CHs. The alkyl carbocation formed from alkene, alcohols or alkyl halides and act as an electrophile in an Friedel- Crafts alkylation reaction.Reaction Intermediates [ ( ; AICI; oh Hee alc + SHC —— 3 HC’ Mechanism: CS + Bete _+ or frac) 2 R R C.F — OF Ce + | no] or g Ina similar manner (R-C20: acyl carbocations formed from acyl halides or acid anhydrides act as electrophile in Friedel Crafts acylation. CocHs AIC + CH;COCI Ho. OH HO. OH ni + CH,CocL —*> ‘OCH, 4. Rearrangement of carbocation: Molecular rearrangements involving carbocations as reactive intermediates are very common in organic chemistry. The 1, 2-shift ofa migrants, to an electron-deficient carbon atomis the most widespread. ® fF pe ROR UR Rw R roe — SOW = Pe 0 Re 7 oF = ‘The 1, 2-shift of either H or alkyl occur in cases where a more stable carbocation can results. 4.2 Carbanion A carbanion can be considered as a species containing a trivalent negatively charged carbon. (A) Structure and stability of carbanion: Carbanion are considered to be derived by the heterolytic fission of the C-X bond in an organic molecule, in which carbon is more electronegative than X. iq =Reaction Intermediates i i e nex —_— ae? +X H H (Cis more electronegative than X)__Carbanion The shape of simple carbanions is determined on the basis of a number of experiments is found to be pyramidal, similar to that of imines. These species invert rapidly at room temperature, passing through @ higher energy planar form in which the electron pair occupies a p-orbital. wl i a —= wha eS Less than 109.5” However, when the carbanion is stabilized by delocatization, it assumes "hybridization for effective resonance. In practice any organic compound having a C-H bond can donate a proton to a suitable base, the species obtained as a result is the carbanion, 9 ® RgC-H + B: ==RC + BH ‘A carbanion possesses an unshared pair of electrons and is therefore a base. Thus, the carbanion mayaccept a proton to give its conjugate acid, Infact, the stability of a carbanion depends on the strength ofthe conjugate acid. The weaker is the acid, the greater is the basic strength and therefore lower will be the stability of the carbanion. Following table (table 2.1) shows the conjugate base obtained from the corresponding acidalong, with pXa values. ‘Table: Relative stability of the carbanions: ‘eid Base pKa RCHCN ROHN B ie wel z ArsCH are 315 4 Arche AnicH? BS PCr paces B HyC=CH, Homo? a 4 Cyclopropane R 46 Hor Cayce a ‘The carbanion being electron rich are very reactive intermediates and are readily attacked by electrophiles (clectrons-deficient reagents). The stability of carbanion is increased if'an electron-attracting group (like CEN or carbonyl) is present in the molecule. However, the stability is decreased ifan electron-releasing group is, present in the molecule. Thus, 3°<2°< iis the order in solution due to destabilization of e-donating alkyl ‘groups, Like carbocations, the carbanions are also stabilized by resonance. Thus, benzyl carbanion is more sable than ethyl carbanion. The stabilization by resonance is due to the delocalization of the negative charge, whichis distributed over other carbon atoms. The canonical forms of benzyl carbanion are given below. €Reaction Intermediates b—-—--5- Canonical structures of benzyl cafbanion ‘The stability of the carbanion is found to be in the order: Benzyl> vinyl> phenyl> cyclopropyl> ethy|> n-propyl> iso-butyl > neopentyl> cyclobutyl> eyclpentyl ‘The stability ofthe carbanion when a functional group (X) is present in the a-position, is ofthe order: NO, > RCO > COOR > SO, > CN~ CONH, > halogens > H>R Carbanion increase in stability with an increase in the amount of s’ character at carbanionic carbon, Thus the order of stability is: e 9 Re > RCH» Ar > RxC—CH, Ifthe unshared pair of a carbanion is involved in ring current and system becomes aromatic, thus, carbanions became greatly stabilized. D—-Ce— L»-O—G (B) Generation ofcarbanions: Following methods are generally used for their generation. | (1) Abstraction of H by a base: Anappropriate organic substrate having C-H bond on treatment witha suitable base results in the abstraction of hydrogen to generate a carbanion, 2 CH, Nos Nos Base OY HoH H | (2) From unsaturated compounds: Addition ofa nucleophile to C=C double bond generates a carbanion, 3) From alkyl halides: Reduction of carbon-halogen bond by metal yields carbanion, Reaction of alkyl halide with Mg turningin presence of anhydrous ether as solvent generates Grignard reagent. The alkyl group in Grignard reagent, behaves like a carbanion, Rox + Mg 8, vex | | 3 R—-G==CHe + Nu ———> R—CH—CH,—Nu aS |Reaction Intermediates (C) Reactions of carbanions: Carbanions take part in the usual types of reactions, v ete, addition, elimination, displacement, rearrangement (1) Addition reactions: The carbanions being electron rich behave like nucleophiles. These add to the carbonyl group for example aldol condensation, claisen condensation, Perkin reaction etc. (2) Elimination reactions: Carbanions are involved as intermediates iE, elimination reactions, ° Base OF ChCHCF; "= cLCcrs ——~ c,0=CF2 In decarboxylation, the loss of CO, from carboxylate anion is believed to involve a carbanion intermediate, ‘which acquires a proton from solvent or other sources, * oe So-LR Slow, co, + R ra RH oO ‘The anion of B-keto acids can undergo facile decarboxylation. g & q ® c + onl he cur Scns e spe Aacooty —> C0, + (3) Displacement reactions: ‘The carbaniors are involved in a number of displacement reactions. The synthetic applications off-ketoesters (eg. diethyl malonate) and 1,3-diketones (e.g. acetylacetone) are due to the formation of the reactive ‘intermediate, carbanion, Hagges oO RBI athocts Ir FO pug 00H ores Plame ®0 6 sco Oa _NaOCAHS Na HE: "yoo 0 LR sycd Shay, —NOCats eg ben Hye gio +B Carbanion The alkynide carbanion undergoes alkylation ina similar manner. NH ©® Rb HC=CH === HC=CNa ——> HCSC-R + NaBr alkyne sodium alkynide alkyneReaction Intermediates Gy 4.3 Free Radicals A radical (often, but unnecessarily called a free radical) is an atom or group of atoms that have one or more. unpaired electrons. Thus, carbon radicals have only seven valence electrons, They readily react with©, , thas their reactions nust be carried out under an inert atmosphere. : radical is paramagnetic and so can be observed by electron spin resonance (e.s.r) spectroscopy. 2: are often uncharged (neutral) but radical cations and radical anions also exist. (A) Structure and stability of free radicals: Radicals are planar in configuration but the energy difference between pyramidal and planar forms very small a ny Q ay me @ Se ® oy (Planar) (Pyramidal) ‘The stability of radical depends upon (i) the nature of the atom that is the radical centre; (ii) the electronic properties ofthe groups attached to the radical. As in the case af carbocations, the order of stability of free radicals is: tertary> secondary > primary methyl This can be explained on the basis of hyperconjugation asin the case of carbocation. The stability ofthe free radicals also increases by resonance possibilities, Thus, allylic and benzylic free radicals are more stable and less reactive than the simple alkyl radicals, This is due to the delocalization of the unpaired electron over the p orbital system in each case. } H,C2Son—tH, -——> 6-H, Canonical structure of allyl radical. Gre CH, CHp la Hy S — — — — ‘The decreasing order of stability of few radicals is as follows: CH CH H (> A when eon > aka > benzyl ally tertiary secondary primary Methyl Vinyl alkynyl phenyl + Thestability ofa radical increases as the extent of potential delocalization increases. Therefore, PhCH is ‘more stable than PhCH, and Ph,C" is a reasonably stable radical, + Adjacent functional groups, electron-withdrawing or clectron-donating, both seem to stabilize radicals. ° . ° AL Aa Aw JReaction Intermediates Certain radicals have rigid molecular structures with fixed bond angles and dihedral angles. These are known as bridge head radicals and have pyramidal structure. This has been supported on the basis of physical and chemical evidences. © (B) Generation of free radicals: ‘The homolytic cleavage of.a covalent bond generates a pair of free radicals. Energy in the form ofultraviolet- visible light, heat, or some other formis needed to break-a covalent bond. ALB Honolvie A+B ssi I) 7 Radicals Example: gc + Ag ——> 2k Ago “Tighenyimetyl chloride Tiphenyimethy| redial The following table lists standard bond energies (D) for the C-C, C-O and C-H bonds commonly found in organic compounds, together with bond energies for some weaker bonds that have been found useful for ‘generating radicals. Approximate homolysis temperatures at which half the bonds are cleaved in one hour are also given. Bond | DKealimole | TC Bond | )-Keallmole | T°C | Bond _D-Kealfmole [T°C CC 85 670 0-0 34 160 | C-Cl 49 280 CH 9 850_ NN 39 230 [CI S1___350. ©) 84 680__S-S 55 440 | C-Br 7 480 ‘Table-4.1: Sumerizes some standard bond energies and approximate homolysis teroprature ‘Though the dissociation energies of C-C, C-X, C-O and C-N bonds are quite high, the very weak O-O bonds ofperoxides are cleaved at relatively low temperatures, Organic azo compounds (R-N=N-R) are also easily decomposed to alkyl radicals and nitrogen. The thermodynamic stability ofnitrogen providesan overall driving force for this decomposition. Thus homolysis of several weaker bonds initiate the carbon radical reactions and then subsequent transfer of radical to carbon occurs. Typical initiator are H,O,, dibenzoyl peroxide and aaobisisobutyronitrle (AIBN) GqReaction Intermediates ww CH, oc CHs pew oe . oN A | Berzoyh peroxide (B) Generation of free radicals also takes place by: j 1. Thermolysis: | The radicals are formed by heating the appropriate substrate a suitable temperature. For example, on heating, chlorine forms chlorine radicals. Peroxides form alkoxy radicals, Peresters fragment to acyl radicals, which lose carbon dioxide to give allyl radicals. Azo compounds evolves nitrogen to give pair ofalkyladicals. The | cleavage of bond can be achieved by heating in non-polar solvents or the vapors phase | aftr ——> 2c , Chlorine radical Chlorine min i $k 20 | Peroxide tbutoxy radical O° POR Men ag bhg Oe a 3° R-Ph(benzoyl peroxide) nea ego | i Hee CN Qo SR 40°C OY TCH, AOE Hy" CN +N, mare HC AIBN 2. Photolysis: ‘Compounds having absorption bands inthe visible or near ultraviolet spectrum may be electronicallyexcited to such a degree that weak covalent bonds undergo homolysis. Bond dissociation energy . ee ofa Sata 58 K cal/mol | fale Ye Be + Br 46 K cabimol hy aa | Zh a 36 K calimot I Acetone in vapour phase is decomposed by light having a wave length of about 320 nm (3200 A). In this reaction two molecules of methyl free radicals are generated. Iq[ Reaction intermediates oO Oo i ly + A ha te Gy + «dc, — co + CH, Hye Hs Certain other species that undergo easily photolysis ae alky nitrites and alkyl hypochlorites. Both these molecules generate akoxyradicals, | R-OSNO Ro + NO Alkyl nitrite R-oSc) RO+ Gl Alkyl hypochlorite (1) Redox reactions: Anelectron can be removed from an anion, and the process is known as oxidation process. In redox reactions there is one-electron transfer in generating the free radicals. The process is known assingle electron transfer (SET) reduction. For example, the phenoxide ion is oxidised by Fe" to give the phenyl oxygen radical and the Fe" is co-reduced to Fe, & . xX —~- Xt e 2 6 @ cr + Fee Set otton (TY ie ® fs X+e—~>x ‘The source ofsingle electron transfer is the metal ion (e.g, Cut, Fe* etc). ‘The Fe** ion can reduce hydrogen peroxide to hydroxy! radical and hydroxide ion. Themixtureof H,O, and Fe isknown as Fenton’s reagent. The effective oxidizing agent is the hydroxyl radical, HO” : 8 woe + Fett SETroduation, G44 Gy 4 pes of peroxide (b) The autoxidation of benzaldehyde is also catalysed by metal ions which are capable of single electron transfer. 9 7 i + Fee ——>ph— H (©) Stable phenoxy radical can also be generated by one electron oxidation with K,Fe(CN),, C. et HY + Fem aa OH MegC. Ces Fo(CN)g MOC Mes CMey CMes (@ Gr ions are used for the decomposition of acyl peroxide. " 9 9° 6A + Cut > nN + 08, 4 cr Acyl peroxide Free radical Gq =Reaction Intermediates This is a convenient method for the generation of ArCOO’ radicals especially because in thermolysis, the ArCOO radicals further decomposes to Ar +CO,. (f) Cut also finds application in Sandmeyer reaction, involving decomposition of diazonium salts. In this reaction the free radical, Ar, is formed as an intermediate. ° ANNa+ ci CUCL acl + Ne ‘The dimerization of carbanions with iodine also takes place via a free radical 8 . 2(CH;CO),CH. —2—» 2(CH,CO),CH ———> (CH3CO),CH—CH(CoCH,), Kolbe reaction for the synthesis ofalkanes also involves the radicals as intermediate, Examples: @2Rco8. @ 2002, of 2RCOO—£. 2RCOO 2aR— RR ° . : . (CHACH),COO =2— cHyCH,),cod 622. cHs(cHa)sGHe (H20HCH)sGr, ——~ cH (CHLH, Radicals are also formed as intermediates in pinacol reduction with sodium or magnesium and in acylion condensation. (©) Classification of radical: A radical ion isa free radical species that carries a negative charge or radical positive charge, radical cations. When a neutral, spin-paired species gains a single electron it becomes both a radical and an anion, a radical anion. Likewise, when a neutral, spin-paired species loses an electron it becomes a radical cation, Radical anions and radical cations are dual classified as both radicals and lewis acid / base species. ++ [Cl Benzene radical anion +s [C|’ Benzene radical anion Radical cations and radical anions are known in the gas phase. They are routinely generated and studied in the complementary techniques of mass spectrometry and negative ion mass spectrometry. (a) Radical anion: Many aromatic compounds can undergo one-electron reduction by alkali metals (such as Na, Lietc.). For example the reaction of naphthalene with sodium in an aprotic solvent yields the naphthalene radical anion - sodium ion salt. In the Birch reduction radical anion is protonated in the presence of a proton source. For example, anthracene radical anion forms mainly (but not exclusively) 9, 10-dihydroanthracene, (b) Radical cation: Cationic radioals are much less stable and noticed prominently inmass spectroscopy. Whena molecule in gas phase is subjected to electron ionization, one electron is abstracted by an electron in the electron beam to create a radical cation M* *, This species represents the molecular ion or parent ion, which on fragmentation gives a complex mixture of ions and uncharged radical species. For example the methanol radical cation fragments into a methyl cation CH,’ anda hydroxy! radical. Secondary species are generated from proton gain (M+1) and proton loss (M-1). =Reaction Incermediates (D) Reactions of radical: Radicals are very reactive reaction intermediates and their half-life period is very short, Some ofthe reactions of radicals are given below. (1) Substitution Reactions: Halogenation of alkane: . The reaction of methane with chlorine in presence of UV light gives a mixture of methyl chloride, methylene chloride, chloroform and carbon tetrachloride. When excess of chlorine is used and by prolonging time of the reaction, the final product is predominantly carbon tetrachloride. onc! + ol, LN ISM CHoch + CHC, + CCl ‘The free radical halogenation of alkanes take place in three steps, i, initiation, propagation and termination. cy = 26) niiavon i : ni . a+ aa CH + HCI 4 matryt tee resial | propagation Ch + CHy CHCl + Cl a+ a —=* cre Cl + CHy;—— CHy-cl > Termination Gy + GH; ——~ CHy—CHs (2) Radical defunctionalization reactions: Dehalogenation: Dehalogenation of hatoalkanes (R-X) is carried out often with trialkyltinhydrides in presence of AIBN, The reactivity of R-X is: R4>R-Br> R-Cl, (R-F being inert); tertiary > secondary > primary> aryl or vinyl OH2Br CH n-Bu,SaH/AIBN =e Mechansim: Spm beady CN CN by H > + n-Bu;Saq_——> ei + n-Bu;Sn* CN CNReaction Intermediates G 44 HBr meBusSa" + aa + n-BuySnBs Cy | chy H 5 yx — + cN Carbene Carbenes are uncharged, electron deficient molecular species that contain a divalent carbon atom surrounded bya sextet of electrons . Though non-bonding electron pair on the carbon atom gives carbenesnucleophilic character, Butasa nile, the electrophilic character dominates carbene reactivity. ‘The parent species, :CH, is knownas methylene, CCI, isknown as dichlorocarbene, However, it canalso be called dichloromethylene, x :CCl, Dichlorocarbene or dichloromethylene Names for acyelic and cyclic hydrocarbons containing one or more divalent carbon atoms are derived fromthe name of the corresponding carbon chain using the suffix -ylidene. H,C=Ct CHy=CHCH? @ Ethenylidene Prop-2-n-I-ylidene Cyclohexylidene (A) Structure and stability of carbene: ‘When two nonbonding electrons are spin-paiced then carbene isin singlet state but if they are unpaired then carbene is in riplet state. There is no magnetic moment for singlet state. On the other hand triplet state has magnetic moment, The substituents affect the; ond multiplicity, wt oe ae om < 9 hybridized “ ve si ye E et 109 *H on™ == He oN Beat methylene Bont methylene Singlet o of carbene Triplet state of On ‘Thus singlet carbene is carbocation-like in nature with trigonal planar geometry. Since the triplet carbene is 8

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