REACTION INTERMEDIATES & MECHANISM

1. REACTION INTERMEDIATES & MECHANISM Presented By JasmeenQuadir KV No. 3 Bhopal

2. Reaction Intermediates Most of the organic reaction occur through the involvement of certain chemical species. These are generally short – lived (10-6 second to a few second ) and highly reactive and hence cannot be isolated. These short –lived highly reactive chemical species through which the majority of the organic reactions occur are called reactive intermediates. Some examples of reaction intermediates are: Carbocations, Carbanions, Free- radicals, Carbenes, Nitrenes.

3. Carbocations Chemical species bearing a positive charge on carbon and carrying six electrons in its valence shell are called carbocations or carbenium ions. By heterolytic cleavage of the covalent bonds in which the leaving group takes away with it the shared pair of electrons (of the covalent bond). For example. (CH3)3C ─ Cl → (CH3)3C+ + Cl- tert –Butyl carbocation tert –Butyl chloride

4. Stability • The stability of carbocations follow the order - • 3° > 2° > 1° > methyl. • This order of stability can be explained on the basis of the following factors: • Inductive Effect • Resonance Effect • Hyperconjugation Effect

5. Inductive effect • More the number of alkyl group on the carbon atom carrying the +ve charge, greater would be the dispersal of the charge and hence more stable would be the carbocation. Thus, the stability of the carbocationsdecereases in the order: 3°> 2°> 1°> ; H H H R > > > C+ C+ C+ C+ R H R R R R H H Stability decreases as +I-effect of the alkyl group decreases Methyl carbocation 30 10 20 + + + + + (CH3)C > CH3CHCH3 > CH3CH2CH2 > CH3CH2 > CH3

6. (b) Resonance effect Carbocations in which the +vely chared carbon atom is attached to a double bond or a benzene ring are stabilized by resonance. CH2 CH ─ CH2↔ CH2 ─ CH CH2 + + (Allyl carbocations is stabilized by resonance) More the number of phenyl group, greater is the stability. (C6H5)3C+ > (C6H5)2CH+ > C6H5CH2+

7. Hyperconjugation effect • Tert – Butyl carbocation has nine α-hydrogens and hence nine hyperconjucation structures. H  HCC CH3   H C H3 H+ HCC CH3   H CH3 H  H+CC CH3   H CH3 H  HCC CH3  H+ CH3 +

8. The stability of the various carbocations decreases in the order: (C6H5)3C+> (C6H5)2CH+ > (CH3)3C+ > C6H5CH2+ > (CH3)2CH+ > CH2 = CH ─ CH2+ > RC = CH2 > CH3CH2+ > RCH = CH+ > C6H5+ > CH3+ > HC ≡ C+ +

9. Reactivity The order of reactivity of any chemical species is reverse that of its stability. Therefore the order of reactivity of carbocations follow the sequence: 1°> 2°> 3°>

10. Orbital structure The three sp2-hybridized orbitals of this carbon form three σ-bonds with monovalent atoms or groups lie in a plane are inclined to one another at an angle of 120°. EMPTY p-ORBITAL R  C+ R 1200   sp2 – HYBRIDIZED CARBON R Orbital structure of carbocations

11. Carbanions Chemical species bearing a negative charge on carbon and possessing eight electrons in its valence shell are called carbanions, - HO- + H ─ CH2 ─ CHO → H2O + CH2 ─ CHO : Hydroxide ion Acetaldehyde carbocation Acetaldehyde ion H2N- + H─ C≡C ─ H → NH3 + C≡C─H Amide ion Acetylene

12. Stability • Inductive effect • The stability of simple alkyl carbanions follow the order: CH3- > 1°> 2°> 3°. H R H H > > > C:- C:- C:- C:- H R R R R H H R Methyl carbonion 10 20 30

13. (b) Resonance effect Allyl and benzyl carbanions are stabilized by resonance. CH2 CH ─ CH2 ↔ -CH2 ─ CH CH2 - (Allyl carbanion is stabilized by resonance) - - :CH2 :CH2 CH2 CH2 CH2 -: :- (Benzyl carbanion is stabilized by resonance) - : (C6H5)3C- > (C6H5)2CH- > C6H5CH-2

14. s- Character • Stability of the carbanion increases with the increase in s- character of the carbon carrying the –ve charge. R ─ C ≡ C- > R2C = CH- > R ─ CH2- 50% s- character 25% s- character 33% s- character

15. Reactivity The order of reactivity of carbanions is reverse of the order of stability, 30 > 20 > 10 > CH-3 Orbital structure The structure of simple alkyl carbanions is usually pyramidal just like those of ammonia and amines. The carbon atom carrying the negative charge is sp3-hybridized. Three of the four sp3-hybridized orbitals form three -bonds with monovalent atoms or group while the fourth sp3 –orbital contains the lone pair of electrons. The carbanions which are stabilized by resonance are planar. In these carbanions, the carbon atom carrying the –ve charge is sp3 – hybridized. Thus, whereas (CH3)3C- is pyramidal, allyl carbanion is planar.

16. Orbital structure sp3 - ORBITAL LONE PAIR . . C-  R   sp3 – HYBRIDIZED CARBON R R Orbital structure of carbanions

17. Free Radical A free radical may be defined as an atom or a group of atoms having an odd or upaired electron . hv or  Homolytic cleavage Cl ─ Cl Cl ─ Cl Chlorine Chlorine free radicals Classification R  R ─ CH2 Secondary (20) R  R ─ C─ R Tertiary (30) R ─ CH2 Primary (10)

18. Stability The order of stability of free radicals is the same as that of carbocations. 3°> 2°> 1°>. The stability of the various free radicals in the order. CH3  CH3 ─ C─ CH3 tert – Butyl free radical (30) CH3  CH3 ─ CH Isopropyl free radical (20) (C6H5)3C > ( C6H5)2CH > C6H5CH2 > CH2=CH─CH2 > (CH3)3C > (CH3)2CH > CH3CH2 > CH3 > CH2=CH > HC≡C > > > CH3 Methyl free radical CH3 ─ CH2 Ethyl free radical (10)

19. Orbital structure Alkyl free radical like carbocations are planar chemical species. The only difference being that in carboctions, the unhybridized p-orbital is empty while in the free radical, it contain the odd electron. p-ORBITAL . UNPAIRED ELECTRON R  C 1200 R   sp2 – HYBRIDIZED CARBON R Orbital structure of free radicals

20. Mechanisms of nucleophilic substitution reaction There are two type of nucleophilic substitution reaction: • SN1 Mechanism (unimolecularnucleophilic substitution) • SN2 Mechanism (Bimolecular nucleophilic substitution)

21. SN1 Mechanism (unimolecularnucleophilic substitution) IN this type, the rate of reaction depends only on the substrate (i.e., alkyl halide) and the reaction id of the first order change. Rate  [Substrate] or Rate = k [RX] THIS TYPE OF REACTION PROCRRDS IN TWO STEP AS:

22. STEP 1. The alkyl halide undergoes heterolytic fission forming an intermediate, carbocation. This step is slow and hence is the rate determining step of the reaction. R ―X R+ + X- Slow step Carbocation CH3  CH3  C  X  CH3 CH3  CH3  C+ X-  CH3 Slow step Tert. butyl halide Carbocation

23. STEP 2. The carbocation ion being a reactive chemical species, immediatrly reacts with the nucleophile [:Nu- ] to give the substitution product. This step is fast and hence does not affect the rate of reaction. R +― :Nu-R― Nu Fast step CH3  CH3  C+ + OH-  CH3 CH3  CH3  C  OH  CH3 Nucleophile Tert. butyl carbocation Tert. butyl alcohol

24. If the alkyl halide is optically active, then the product is a racemic mixture. Thus, racemization occurs in SN1 reactions. The order of reactivity depends upon the stability of carbocation formed in the first step. Due to stable nature of 3°carbocation, the SN1 reaction is favored by heavy (bulky) group on the carbon atom attached to halogens. R3C ― X > R2CH ― X > R ― CH2 ― X > CH3 ― X Tertiary (30) Secondary (20) Primary (10) and nature of carbocation in substrate is: SN1 Order: Benzyl > allyl > 30 > 20 > 10 > methyl halides

25. SN2Machanism (Bimolecular nucleophilicsubsititution): In This type, the rate of reaction depends on the concentration of both substrate (alkyl halide) and the nucleophilic; the reaction is said to be SN2 , the second order change Rate  [Substrate] [Nucleophile] or Rate = k [ RX ] [ :Nu- ]

26. Hydrolysis of methyl chloride is an example of SN2 reaction and high reaction concentration of the nucleophile (OH-) favours SN2 reaction. The chlorine atom present in methyl chloride is more electronegative than the carbon atom. Therefore C ― Cl bond is partially polarized. H  H C+ Cl -  H

27. When the methyl chloride is attacked by OH- strong nucleophile from the opposite side of the chlorine atom, a transition state results in which both OH and Cl are partially bonded to carbon atom.  - - HO- - - - - -C- - -- - - Cl  H H O C Cl  H H H H H Transition state H  HO C H + Cl-  H Alcohol

28. SN2 reaction of optically active halides are concerted reactions and configuration of carbon is changed. This process is called as inversion of configuration, complete inversion takes place. This inversion of configuration is commonly known as Walden Inversion. Slow Fast Nu- + R X [Nu ------- R -------- X] Nu  R + X - Transition state CH3 - H3C H O + H O  C H + Br- C  Br H n – C6H13 n – C6H13 (+) Octan – 2 – ol (–) -2 - Bromooctane

29. CH3 X >RCH2  X > R2CH  X >R3C  X Primary Secondary Tertiary The nature of carbocation in substrate is : SN2 order : Methyl > 10 > 20 > 30 > allyl > benzyl halides

30. MECHANISM OF HALOGENATION Halogenation of benzene is an electrophilic subsititution reaction.

31. Step 1.The electrophilic, i,e., halonium ion (Cl+, Br+ or I+) is generated by the action of Lewis acid (FeCl3 or anhyd. AlCl3........etc.) on the halogens. Cl ― Cl + FeCl3 → Cl+ + Fecl-4 (Electrophile)

32. + H Step 2:The electrophile (Cl+) attacks the benzene ring to from an intermediate known as  - complex or a carbocation (arenium ion) which is stabilized by resonance. + Cl+ Cl Slow Chloronium ion Benzene Carbocation + H H H H Cl Cl Cl + Cl + + Resonance stabilized carbocation The formation of intermediate arenium ion (carbocation) is slow and hence is the rate determining step of the reaction.

33. Step 3:The carbocation loses a proton (H+) to the base FeCl-4 to give chlorobenzene. Fast + FeCl3 + HCl + H Cl Chlorobenzene Cl + FeCl-4 This step is fast and hence does not affect the rate of the reaction.

34. Mechanism of hydration of ethene to ethanol Solution :Direct addition of water to ethene in presence of an acid does not occur. Indirectly ethene is first passed through conc.H2SO4 at room temperature to from ethyl hydrogensulphate, which is decomposed by water on heating to form alcohol.   C C + H2SO4   H OH    C C   H OSO3H    CC  + H2SO4 H2O Heat Alkene Alcohol Alkyl hydrogensulphate

35. Mechanism: H2SO4→ H+ + -OSO2OH

36. Step 1:Protonation of alkene to form carbocation by electrophilic attack of hydronium ion (H3O+) H O H + H+ H  H O+  H (H3O+) H  H O+  H      H2C CH2 + H2C+ CH3 + H2 O  Ethene Carbocation

37. Step 2:Nucleophilic attack by water on carbocation to yield protonated alcohal. O+  H  H O H  H   + : CH3 CH2 + CH3 CH2 Ethyl Carbocation Protonated alcohol

38. O H +  H Step 3:Deprotonation (loss of proton) to from an alcohal.  OH  H  CH3  CH2 OH + H3O+ : CH3 CH2 +

39. Mechanism of Aldol Condensation (Acidity of α – Hydrogen) The formation of aldol proceeds through the following three equilibrium steps:

40. Step 1:The base (OH-) on removes one of the α – hydrogen atom (which is somewhat acidic) from aldehydes and ketones to form the enolate ion which is stabilized by resonance. O O O Slow HO + H  CH2 C  H2O + H H H Carbanion Acetaldehyde  : : : CH2 C CH2 C Enolate ion The acidity of α – hydrogen is due to resonance stabilization of enolate anion.

41. Step 2:The enolate ion ( strong nucleophilic) attacks the carbonyl carbon of second molecule of acetaldehydes (which acts as an electrophile ) to form the anion.  - : O O O CH3 C H +  CH3 C  CH2 C  H : H H CH2C Fast + Acetaldehyde (Electrophile) Enolate ion (Nucleophile)  : : O Anion

42. Step 3: The anion so formed takes up a proton from water to form aldol and the OH-ion is regenerated. :  : O O O CH3 C  CH2  C  H OH + H  OH  CH3 C  CH2 C  H H H Anion + OH- Aldol

43. Cannizzaro’s reaction (With concentration alkali solution) Aldehydes which do not contain α – hydrogen atom, such as formaldehyde (HCHO) and benzaldehyde (C6H5CHO), when treated with concentrated alkali solution undergo self oxidation and reduction, disproportionation. In this reaction one molecule is oxidised to corresponding carboxylic acid at the cost of the cost of other which is reduced to corresponding alcohol. This reaction is called Cannizzaro’s reaction.

44. 2HCHO + NaOH → HCOONa + CH3OH Formaldehyde (50%) Sodium formate Methyl alcohol 2C6H5CHO + NaOH → C6H5COONa + C6H5CH2OH The usual regent for bringing about the cannizzaro’s reaction is 50% aqueous or ethanolic alkali. Ketones do not give this reaction. Benzaldehyde (50%) Sodium benzoate Benzyl alcohol Mechanism : The machanism of this reaction involve hydride ion transfer and one possibility being as follow:

45. Step 1. The OH-ion attack the carbonyl carbon to form hydroxy alkoxide (Nucleophilic attack) an (I). O C6H5  C + OH-  H O-  C6H5  C OH  H Fast Benzaldehyde Anion (I)

46. Step 2:The anion (I) hydride ion donor to the second molecule of aldehyde. In the final step of the reaction, the acid and the alkoxide ion transfer H+ to acquire stability. O-  C6H5  C OH  H O-  + C6H5  CH  H O C6H5  COH Hydride transfer (Slow) Anion (I) Benzaldehyde O + C C6H5  H (Fast) -H+ (Fast) +H+ OH  H C C6H5  H O C6H5  C O- Salt of benzoic acid Benzyl Alcohol

47. Mechanism of esterification of carboxylic acid It is a kind of nucleophilic acyl substitution. The mechanism of esterification involes the following step:

48. Step 1.Protonation of the carbonyl group. In presence of mineral acids (conc. H2SO4 or HCl gas), the carbonyl oxygen of carboxylic acid accepts a proton to form protonated carboxylic acid (I). +    OH O OH    + R C R C R C + H+ OH H OH Protonated Carboxylic acid (I) Carboxylic acid

49. Step 2.Nucleophilic attack by the alcohol molecule The electron rich oxygen atom of alcohol molecule attaches itsalf at positively charged carbon atom to form tetrahedral intermediate (II). OH H   R C O R’  OH  H  OH   + : R C R’ + O  + OH Alcohol Tetrahedral imtermediate (II)

50. Step 3:Transfer of proton. Form the resulting intermediate, a proton shifts to –OH and from another tetrahedral intermediate (III). + OH H   R  C O R’  OH OH2  R  C O R’  OH Proton transfer + (III)