Alkyl Halides & Aryl Halides

ALKYL HALIDES & ARYL HALIDES Compounds derived from hydrocarbons by replacement of one or more H-atoms by corresponding no. of halogen atoms are known as halogen derivatives. There are three major classes of organohalogen compounds ; alkyl halides, vinyl halides, and aryl halides. An alkyl halide simply has a halogen atoms bonded to one of the sp3 hybrid carbon atoms of an alkyl group. A vinyl halide or Aryl halide has a halogen atom bonded to one of the sp2 hybrid carbon atoms or an aromatic ring. They are different from alkyl halides because their bonding and hybridization are different. Alkyl halides may be further classified as mono, di, tri,....... and primary, secondary or tertiary halides. C2H5X Monohaloalkane sp 3 CH2X CH2X Dihaloalkane CH2X H CHX H C CH2X Trihaloalkane X Primary (1º) R' C Benzylic 1º halide X H sp CH2X Allylic 2º halide R' Secondary (2º) sp3 3 X sp CH 2X Allylic 1º halide H R' 2 X Vinylic halide R'' C X R''' Tertiary (3º) sp2 X Aryl halide Structure of Alkyl halide : The carbon-halogen bond in an alkyl halide is polar because halogen atoms are more electronegative than carbon atom. Most reactions of alkyl halides result from breaking this polarized bond. The carbon atom has a partial positive charge, making it some what electrophilic. CLASSIFICATION On the basis of nature of hydrocarbon from which they are obtained, hydrocarbon derivatives can be classified as: Halogen Derivatives Alkyl halides Mono halides Primary halide Di-halides Alkenyl halide Tri-halides Secondary halide Tertiary halide Alkynyl halide Tetra halides Aryl halide (a) Alkyl halides : Halogen derivative of alkanes. (b) Alkenyl halides : Halogen derivative of alkenes. (c) Alkynyl halides : Halogen derivative of alkynes (d) Aryl halides : Halogen derivative of arenes (aromatic) Alkyl halides : They are further classified on the basis of halogen atoms introduced in the molecule. e.g. (i) Mono halides: These involves replacement of one H-atom by halogen atom. General formula CnH2n+1X Ex. CH3Cl Methyl chloride (Chloro methane) CH3CH2Br (ii) Ethyl bromide (Bromo ethane) Dihalides : Replacement of two H-atom by halogen atoms. General formula CnH2nX2 Ex. CH2X2 Methylene dihalide CH2X Ethylene dihalide or Vicinal dihalide CH2X CH3 Ethylidene dihalide or geminal dihalide CHX2 (iii) Ex. Trihalides : Replacement of three H-atoms by halogen atoms. General formula - CnH2n-1X3. CHX3 Trihalo methane or haloform (iv) Tetra halide and Perhalo compounds : Replacement of 4 H-atoms by halogen atoms (in CH4  CCl4)  Tetrahalides. When all the H-atoms from an alkane are replaced by halogen atoms, then the compounds are called as perhalo compound - General formula CnH2n–2X4 (tetra halide). CH4  CX4 (Per halo methane) C2H6  C2X6 (Per halo ethane) MONO HALIDES : These are classified on the basis of nature of C-atom carrying the halogen atom . (A) Ex. CH3—X (B) Ex. Primary halide or 1° alkyl halides : Halogen atom attached with a primary or 1° C-atom. Halo methane or methylhalide CH3—CH2—X Halo ethane or ethyl halide CH3—CH2—CH2—X 1-Halo propane or n-propyl halide Secondary or 2° alkyl halides : Halogen atom linked with 2° C-atom. CH3 CH 2-halo propane or Iso propyl halide CH3 X CH3 CH CH2 X CH3 2-halo butane or Sec. butyl halide ALKYL HALIDES & ARYL HALIDES (C) Tertiary halide or 3° alkyl halide : halogen atom linked with 3° C-atom. Ex. (tert.alkyl halide) Isomerism : Alkyl halides shows position and chain isomerism C3H7Cl  CH3CH2CH2Cl Ex. CH3CHCH3 Position isomers Cl Ex. (a) C4H9Cl (b) (c) CH3CH2CH2CH2Cl CH3 CH3 CH3 1 - chloro butane 1-chloro-2-methyl propane CH CH2Cl CH 2 CH CH 3 2 - chloro butane Cl CH3 CH3 (d) C Cl 2-chloro-2-methyl propane CH3 a, b  Chain isomers a, c  Position isomers a, d  Chain and position isomers b,c  Chain and position isomers b, d  Position isomers c, d  Chain isomers Reactivity order : The order of reactivity of alkyl halides is - RI > RBr > RCl > RF Bond energy values : C–I ( 57. 4), C–Br (65.9), C–Cl (78.5) and C–F (105.4) K.cal/mole C–I bond is most reactive because lower energy is required to break the bond. On the basis of nature of alkyl group the reactivity order of alkyl halide is - tert > Sec. > Primary Since alkyl groups, are electron repelling or electron releasing, larger no. of alkyl groups on C-atom of C–X greater is the electron density on C-atom hence ease in release of X atom as X – ion (+ I effect of alkyl group) Alkyl halides are generally more reactive than the corresponding alkanes due to the presence of polar covalent ( ) bond. So alkyl halides ( R–X) undergo nucleophilic substitution reaction. 1 The centre for attacking Nu is + C atom GENERAL METHOD OF PREPARATION OF MONOHALIDES : 1. By direct halogenation of alkanes : R—H + Cl2 U.V. light R—Cl + HCl (excess) 2. By the addition of H—X on alkenes : R—CH CH2 CHR + HX  CH2 + HX CH3–CH CH2 + HX RCH2—CHXR  CH3 —CH2X  CH3 CH CH3 X Isopropyl halide 3. By Alcohols : (a) By the action of hydrogen halides : Ex. R—CH2—OH H-X ZnCl2 RCH2—X Mechanism : In this reaction intermediate carbocation is formed so rearrangement ( H – shifting or CH 3– shifting) can take place. ZnCl2 act as dehydrating agent and absorbs H2O from the reaction so good yield of halide is obtained. Also it generates H+ from HCl. HCl + ZnCl2  ZnCl13 + H  Reactivity order for alcohol : Reactivity  stability of intermediate carbocation , so reactivity order : Tert. alc. > Sec. alc. > Pri. alc. Reactivity order of H—X is : HI > HBr > HCl HI is maximum reactive so it reacts readily with 1°, 2° and 3° alcohols. R—OH + HI  R—I + H2O HCl and also 1° alcohol are less reactive so ZnCl2 or some amount of H2SO4 is needed to increase the reactivity. Ex. CH3—CH2—OH + HCl ZnCl2 At normal condition : CH3 —CH2—Cl CH3—CH2—OH + HCl × (no reaction) Note : HCl + ZnCl2 is called as lucas reagent, alcohol gives turbidity with lucas reagent. Reactivity towards lucas reagent (difference in 1°, 2° and 3° alcohol). Time to give turbidity 1° alcohol 2° alcohol 3° alcohol in 30 min. in 5 min. in 1 min. ALKYL HALIDES & ARYL HALIDES (b) By the action of phosphorus halides (SN1 mechanism) : R—OH + PCl5  R—Cl + POCl3 + HCl 3R—OH + PCl3  3RCl + H3PO3 PBr3 and PI3 are less stable, thus for bromides and Iodides, ( P + Br2) Or ( P + I2) mixture is used. (c) By reaction with thionyl chloride - (Darzen's procedure) ( SN1 and SN2 mechanism) : R—OH Pyridene 1 mole + SOCl2 One mole R— Cl + SO2 + HCl One mole Because of less stability of SOBr2 and SOI2, R—Br and RI does not obtained by this method. 4. Borodine – Hunsdicker's reaction : R—COOAg Silver salt of + X2 R—X + CO2 + AgX (Cl2 or Br2) a fatty acid 5. By halide exchange : R–Cl or R—Br + KI  Acetone R–I + KCl or KBr (Conant finkelstein reaction) 2CH3Cl + HgF2  2CH3–F + HgCl2 (Swartz reaction) R– I and R—F can be prepared by this method only. 6. By reaction of alkanes with sulphuryl chloride (SO2Cl2) : light R—H + SO2 Cl2 organic peroxide R—Cl + HCl + SO2 PHYSICAL PROPERTIES (a) The lower members CH3F, CH3Cl, CH3Br , C2H5Cl and C2H5F are gases at room temp. CH3I and members upto C18 are colourless sweet smelling liquids. (b) Higher B.P. than parent alkanes. Decreasing order of B.P. is : R – I > R—Br > R—Cl > R—F among isomeric R—X decreasing order of B.P. is : Primary > Secondary > tertiary (c) R—F and R—Cl lighter than water R—Br and R—I heavier than water Decreasing order of density is : R—I > R—Br > R—Cl > R—F (d) R—X are polar co-valent compounds but insoluble in water because they can not form H–bonds. They dissolve in organic solvents. (e) R—X burns with a green flame due to interaction of X with Cu wire. (Beilstein test) (f) The stability order is : R—F > R—Cl > R—Br > R—I R—I is least stable and darken in light due to photodecomposition. 2R—I R—R + I2 CHEMICAL PROPERTIES : A. NUCLEOPHILIC SUBSTITUTION REACTION (SN) : Due to electronegativity difference the C X bond is highly polarised bond. Thus the C-atom of the  bond becomes centre to attack by a nucleophile (Nu ) . 1 X1 ion from R—X molecule is substituted by a Nu . i.e.SN reaction are the most common reactions in R—X. 1 R—X + Nu R—Nu + X1 These may be takes place by two ways (a) SN1 mechanism (b) SN1 mechanism R2 Reactivity order is : R1 C X R3 Mechanism of SN1 and SN2:  SN1 (Tertiary) > R1 CH X R2 SN1and SN 2 (Secondary) > R1CH2 X SN 2 (Secondary) SN1 Mechanism : SN1 stands for uni molecular nucleophilic substitution. The mechanism involves two steps. Consider the hydrolysis of tert. butyl bromide with aqueous NaOH. Step 1: The alkyl halide ionises to give a planar carbonium ion. The carbonium ion is planar because the central positively charged carbon is sp2 hybridized. Step-2 : The nucleophile can attack the planar carbonium ion from either side to give the product. ALKYL HALIDES & ARYL HALIDES (i)  Ionisation is the rate determining step because it is the slow step. In other words, the rate at which alcohol is formed should depend upon the concentration of tertiary alkyl halide alone. Rate = K[R3C—Br] It is obvious that the reaction follows first order kinetics, therefore reaction is called SN1 . (ii) The reactivity order for SN1 reaction stability of carbocations formed by halides.  reactivity order of halides (SN1) varies as follows : Benzyl halide > Alkyl halide > 3°halide > 2° halide > 1° halide > methyl halide. (iii) Remember that in case alkyl halide is optically active, SN1 reactions lead to racemisation. Energetics of the SN1 Table - : Dielectric constants () and ionisation rates of t-Butylchloride in common solvents Solvent  Relative rate H2 O CH3 OH C2 H5 OH (CH3 )2 CO CH3 CO2 H 80 33 24 21 6 8000 1000 200 1 – SN2 mechanism : SN 2 stands for bimolecular nucleophilic substitution. In this type of nucleophilic substitution reaction, there occurs bond making and bond breaking simultaneously. (i) Reactivities of alkyl halides in S N2 substitution is governed by steric factors. The bulkier the group, that less reactive it will be. (ii) Reactivity order of alkyl halide varies as follows : CH3X > 1°halide > 2°halide > 3° halide (iii) The order of reactivity among 1° alkyl halides is : CH3X > C2H5X > C3H7X etc. Remember that in case alkyl halide is optically active, SN2 reactions lead to Walden inversion. (iv) Thus in short 3° alkyl halides react by S N1 , 1° by S 2 and 2° by either or both of them SN1 and SN2 N depend upon the nature of the alkyl halide and the reagent. (v) For a given alkyl group the order of reactivity is - (for SN1 and SN2 both) : RI > RBr > RCl > RF (vi) In addition to substitution reaction alkyl halide also undergo elimination reactions to form alkene with the removal of a molecule of hydrogen halide (dehydrohalogenation). In dehydrohalogenation, hydrogen and halogen atoms are eliminated from two adjacent carbon atoms, the reaction also known as elimination may proceed by E1 & E2 mechanism (analogous to S N1 and S N2 mechanism). The order of elimination reaction is : 3° halides > 2° halides > 1° halides (vii) In general 3° halides tend to react by elimination; 1° halides by substitution and 2° halides by either or both of the reactions. 1 B. ELIMINATION REACTIONS (ER) : Alkyl halides also undergo ER in the presence of base as Nu (Loss of H—X and formation of = bond) 1. NUCLEOPHILIC SUBSTITUTION REACTION ( SN ) : (g) Reaction with KCN and AgCN : R—C N + KX + RNC cyanide (major) ALKYL HALIDES & ARYL HALIDES Ex. (h) Reaction with KNO2 and AgNO2 (i) Reaction with NaOR' (Sodium alkoxide) : (williamson synthesis reaction) R—X + NaOR'  R—OR' + NaX (i) CH3—CH2—Cl + NaOCH3 CH3—CH2—O—CH3 (major) (ii) (iii) (j) Ex. Reaction with NH3 : (i) (ii) (excess) (iii) R –X + NH3 (iv) CH3—CH2—Cl+ NH3 (v) CH3 CH Cl R–NH 2 CH3 + NH 3 R –X R –NH–R R–X CH3—CH2—NH2 + HCl  CH3 CH CH3 + HCl NH 2 (or elimination product) CH3 CH3 (vi) C CH2 Cl + NH3  CH3 CH3 (more reactive) (vii) CH3 (Elimination is more) + Reaction with CH R—X + CH C + NH4Cl C Na :  R—C C Na CH + NaX IF 2. Elimination Reaction : (Dehydrohalogenation) Alkyl halides undergo - elimination on treatment with KOH (alc.) β α R – C H 2 – C H 2 – X + K O H (alc.)  CH3—CH2—CH2—CH2—Br + KOH(alc.) CH3 H Br CH CH CH2 + HX CH3—CH2—CH CH3—CH CH3 R—CH CH2 + HBr CH—CH3 + CH3—CH2—CH CH2 + HBr 2 - butene (80%) 1 - butene (20%) Competition between substitution and elemination reactions : Reactivity order of alkyl halides : E1 - Reaction : 1° < 2° < 3° E2 - Reaction : 1° < 2° < 3° SN 1 - Reaction : 1° < 2° < 3° SN 2 - Reaction : 1° > 2° > 3° Alkyle halides 1° Alkyl halides 2° Alkyl halides 3° Alkyl halides S N2 /E2 S N1 /E1 Mainly give substitution unless sterically hindered alkyl halide or sterically hindered base in which case elimination is favoured Both substitution and elemination, stronger base/ bulkier base or high temp. greater percentage of elimination. Can not undergo SN /E Mainly elimination Both substitution and elimination, high temp greater percentage of elimination. 1 1 Both substitution and elemination high temp. greater of percentage of elimination ALKYL HALIDES & ARYL HALIDES (i) SN2 / E 2 is favoured by high conc. of good neucleophile or strong base. (CH3O1, HO1) Rate of Reaction  (Substrate) (Reagent) (ii) (iii) SN1 / E1 is favoured by low conc. of poor neucleophile or weak base (CH3OH, H2O) If an alkyl halide, undergoes SN2 / SN1 – Reaction then SN2 will be favoured by high conc. of good neucleophile (negetively charged) in presence of polor aprotic solvent . where as SN1 – reaction is favoured by low conc. of poor neucleophile (neutral) is presence of polar protic solvent. Polar protic solvent : H2O, CH3OH, HCOOH. Polar aprotic solvent : DMSO, CH3CN, C2H5–O–C2H5 Ex. CH3CH2CH2—Br + CH3O1 major SN 2 CH3OH CH3CH2CH2—OCH3 + CH3CH E2 Ex. Ex. CH3 Ex. CH3CH2CH2CH2Br + CH3 C CH3 Ex. CH2 minor ONa  CH —CH CH=CH (E2) mech. 3 2 2 Saytzeff rule : According to this rule "The dehydrohalogenation of an alkyl halide results preferentially in the production of more alkylated alkene i.e. more stable alkene. 3. Wurtz Reaction : When a mixture of different alkyl halides, (R1 - X) and (R2 - X) is used a mixture of alkane is formed R1—X + 2Na + X—R2 R1—R2 + R1—R1 + R2—R2 + NaX If 'Zn' is used in place of 'Na' the reaction is called Frankland's Reaction. 4. Halogenation of alkyl halides : CH3—Cl + Cl2 Similarly C2H5Cl 5. 6. Cl2 CH2Cl2 C2H4Cl2  Cl2 Cl2 -HCl  C2H3Cl3  CHCl3 Cl 2 (excess) Cl2 -HCl CCl4 C2Cl6 Reduction : R - X are reduced to corresponding alkane. R—X + 2H Reducing agent (i) CH3CH2Br + H2 Ni (ii) CH3CH2CH2 Br + 2H Zn/HCl (iii) C2H5I + HI Red.P R—H + HX CH3CH3 + HBr CH3 — CH2 — CH3 + HBr C2H6 + I2 Formation of Organometallic compounds : dry ether (i) R—X + Mg  (ii) 2C2H5Br + (iii) 2C2H5Br + Hg(Na) (C2H5)Hg 2NaBr 2Zn RMgX dry ether (Grignard reagent) (C2H5)2 Zn + ZnBr2 Sodium Amalgam (iv) 4C2H5Cl + 4Na / Pb (C2H5)4 Pb + 4NaCl + 3Pb Sodium lead Alloy Tetra ethyl lead (used as antiknocking agent) ALKYL HALIDES & ARYL HALIDES 7. Friedel - Crafts reaction : 8. Action of heat : (i) CH3— CH2 — CH2— Cl At or below 300°C (Rearrangement) CH3 CH CH3 Cl (ii) Uses : (a) As alkylation agent (Wurtz reaction) (b) As synthetic reagent (c) Lower members used as anaesthetic agent, refrigerant or solvent. DIHALIDES General formula CnH2nX2 .Two H - atom of alkanes, replaced by two halogen atoms to form dihalides. Dihalides are classified as : (a) Gem dihalide : The term Gem is derived from geminal means - same position. Two similar halogen atoms are attached to same C - atom Ex. CH3CHX2 CH3 CH3 (b) ethylidene dihalide CHX2 Isopropylidene dihalide (1, 1 - dihalo ethane) (2, 2 - dihalo propane) Vic dihalides : Vic term from - Vicinal means adjacent C - atoms Two halogen atoms are attached on adjacent carbon atom. H Ex. CH2 CH2 X X (c) Ex. CH2 X H C CH CH2 Vic and Gem dihalides are position isomers. H X X ethylene dihalide Propylene dihalide (1,2-dihaloethane) (1,2-dihalopropane) dihalides : Halogen atoms are attached with terminal C - atom. They are separated by 3 or more C - atom . They are also known as polymethylene halides. CH2 CH2 CH2 (1,4-dichloro butane) X Tetramethylene dichloride GENERAL METHOD OF PREPARATION : (a) Gem dihalides : (i) By the reaction of PCl5 on carbonyl compound. O CH3 C H + PCl5  Acetaldehyde Ethylidene chloride O CH3 C Br CH3 + PBr5  CH3 C CH3 + POBr3 Br Acetone (ii) 2, 2 - dibromo propane By addition of halogen acids on alkynes : CH CH + HBr CH2 CHBr  HBr Vinyl bromide (b) Vic-dihalides : (i) By the addition of halogens to alkenes : (ii) By the action of PCl5 on glycols : (c) dihalides : (i) CH2 CH3 CHBr2 1, 1 - dibromo ethane CH—CH2Br + HBr Br—CH2—CH2—CH2Br 1, 3 - dibromo propane (ii) + Cl2  CH2 Cl CH2 CH2 Cl ALKYL HALIDES & ARYL HALIDES (ii)  CH2 + Cl2 CH2 CH2 CH2 Cl Cl Cl (iii) Note : + Cl2 Here  + HCl has less tendency to open the ring. PHYSICAL PROPERTIES : (i) Lower members are colourless, oily liquids with sweet smell. Higher members are solid. (ii) The reactivity of gem dihalides is lesser than vicinal or mono halides. [Reason - in presence of one halogen atom (Strong attracting –I effect) the other halogen atom can not be so easily replaced. (iii) These are heavier than water. CHEMICAL PROPERTIES : (i) Action of KOH(alc.) (Dehydrohalogenation) CH 2X CH 2X (ii) or CH3 CHX2 (i) alc. KOH (ii) NaNH2 CH CH Action of KOH(aq.) (Hydrolysis) It is a distinction test for gem and vic dihalides. (a) Glycol Vic - dihalide. (b) CH3CHXCH2Y Vic-dihalide. 1, 2 - ethane diol. KOH (aq.) CH 3 CH CH 2 OH OH propane - 1, 2 - diol Gem. (iii) Vic. : Reaction with KCN : Gem and Vic dihalide gives different products Gem. : (i) – CN group on acid hydrolysis gives - COOH (ii) Two – COOH group on one C – atom on heating always loose CO2 to form monocarboxylic acid. (iii) Two – COOH group on vic. C – atom on heating loose H2O to form anhydride. (iv) Dehalogenation : Vic. Gem. CH3— CH2CH Br2 + Zn CH3 — CH2— CH CH — CH2— CH3 + ZnBr2 (Twice Carbon Product)    - dihalide. cyclopropane GRIGNARD REAGENT General Method of Preparation : Grignard reagents are prepared in the laboratory by the action of alkyl halides on magnesium metal in the presence of dry ether. R – X + Mg dry ether RMgX (Grignard reagent) (Alkyl magnesium halide) The ease of formation of Grignard reagent is in the order RI > RBr > RCl Ether is used to dissolved the Grignard reagent by coordination. ALKYL HALIDES & ARYL HALIDES Chemical Reactions : ARYL HALIDE If halogen atom is directly attached to the benzene ring, then compound is called as Haloarene. Ex. Cl CH3 CH3 Cl Cl Cl (Chlorobenzene) (2–Chlorotoulene) GENERAL METHODS OF PREPARATION Halogenation of Benzene : (2,4–Dichlorotoulene) From Phenol : OH Cl  + PCl 5 + POCl3 + HCl (minor) 3C6H5OH + POCl3  (C6H5)3 PO4 + 3HCl (major) Sandmeyer's reaction : N2Cl + CuCl HCl Cl + N2 HBr Br + N2  N2Cl + CuBr  + KI  + N2 + KCl  Cl + CO2 + AgCl Reaction with KI : N2Cl I Balz-schiemann's reaction : Hunsdicker reaction : COOAg + Cl2 Raschig Process : Cl 2 + 2HCl + O2 CuCl   2 + 2H2O CHEMICAL PROPERTIES (i) Chlorobenzene is essentially inert to aqueous sodium hydroxide at room temperature. (ii) Aryl halide are very less reactive than alkyl halides in nucleophilic substitution reactions. (iii) The carbon-halogen bonds of aryl halides are too strong & aryl cations are too high in energy to permit aryl halides to ionize readily SN1 -type process. (iv) The optimal transition state geometry required for SN2 process cannot be achieved. (v) Nucleophilic attack from the side opposite the carbon-halogen bond is blocked by the aromatic ring. ALKYL HALIDES & ARYL HALIDES The Elimination-Addition Mechanism of Nucleophilic Aromatic Substitution (Benzyne) (i) Very stong base such as sodium or potassium amide react with aryl halide, even those without electron withdrawing substituents to give products corresponding to nucleophilic substitution of halide by the base. Cl NH2 KNH2, NH3 –33°C Chlorobenzyne-1- C 14 + NH2 Aniline - 1- C 14 Aniline-2- C 14 Mechanism Step-1 : Elimination stage ; Amide ion is a very strong base and brings about the dehydrohalogenation of chlorobenzene by abstracting a proton from the carbon adjacent to the one that bears the leaving group. The product of this step is an unstable intermediate called benzyne. Step-2 : Beginning of addition phase ; Amide ion acts as a nucleophile and adds to one of the carbons of the triple bond. The product of this step is a carbanion. Step-3 : Completion of addition phase ; The aryl anion abstracts a proton from the ammonia used as the solvent in the reaction. NOTE : The sp2 orbital in the plane of the ring in benzyne are not properly aligned for good overlap thus  bonding is weaker than alkyne. CH3 Cl KNH2 NH3 (i) O-chloro toluene CH3 CH3 CH3 NH2 KNH2 NH3 3-Methylbenzyne + NH2 o-Methylaniline m-Methylaniline (ii) CH3 CH3 CH3 NH2 KNH2 NH3 CH3 3-Methylbenzyne KNH2 (iii) Cl NH3 + NH3 o-Methylaniline CH3 p-Methylaniline CH3 CH3 + KNH2 NH3 4-Methylbenzyne NH2 NH2 p-Methylaniline o-Methylaniline Nucleophilic Aromatic Substitution by the addition Elimination Mechanism : (i) The generally accepted mechanism for nucleophilic aromatic substitution in nitro-substituted aryl halides. Cl OCH3 + NO2 p-Chloronitrobenzene NaOCH3 CH3OH + 85°C NO2 p-Nitroanisole NaCl ALKYL HALIDES & ARYL HALIDES (ii) An ortho - nitro group exert a comparable rate-enhancing effect, m-chloronitrobenzyne while much more reactive than chlorobenzyne itself, is thousand of times less reactive than either o-or p-chloronitrobenzene. (iii) The effect of o- & p-nitro substituents is cummulative, as the rate data for substitution with methoxide ion in a series of nitro-substituted chlorobenzene derivative demostrate increasing rate of reaction as : Cl Cl Cl Cl O2N NO2 NO2 NO2 Relative rate : (iv) Chlorobenzene 1.0 1-Chloro-4-nitrobenzene 10 7 × 10 NO2 NO2 1-Chloro-2, 4-dinitrobenzene 2.4 × 1015 2-Chloro-1, 3, 5-trinitrobenzene (too fast to measure) In contrast to nucleophilic substitution in alkyl halides, where alkyl fluorides are exceedingly unreactive, aryl fluorides undergo nucleophilic substitution readily when the ring bears an o-or a p-nitro group. F OCH3 + NO2 p-Fluoro nitrobenzene (v) KOCH3 Potassium methoxide CH3OH 85°C + NO2 p-Nitroanisole (93%) KF Potassium fluoride Indeed, the order of leaving group reactivity in nucleophilic aromatic substitution is the opposite of that seen in alphatic substitution. (vi) Fluoride is the best reactive leaving group in nucleophilic aromatic substitution, iodide the least reactive. X Relative reactivity towards sodium methoxide in methanol (50°C) X = F Cl Br I 312 1.0 0.8 0.4 NO2 (vii) Kinetic studies of many of the reactions described in teh section have demostrated that they follow a second-order rate law. Rate = k[aryl halide] [nucleophile] (viii) Second order kinetics is usually interpreated in terms of a bimolecular rate determining step. F OCH3 + NaOCH3 + NO2 NaF NO2 p-Fluoronitrobenzene Sodium methoxide p-Nitroanisole Sodium Fluoride Mechanism : Step -1 - Addition stage. The nucleophile, in this case methoxide ion, adds to the carbon atom that bears the leaving group to give a cyclohexadienyl anion intermediate. .. :F: .. .. :F: :OCH3 H H .. :OCH .. 3 + H slow H H .. H H NO2 H NO2 p-Fluoronitrobenzene Methoxide ion Cyclohexadienyl anion intermediate Step -2 - Elimination stage. Loss of halide form the cyclohexadienyl intermediate restores the aromaticity of the ring and gives the product of nucleophilic aromatic substitution. .. :OCH3 .. .. :F: :OCH3 .. .. H – H H Fast H H H H NO2 .. – F .. Fluoride ion NO2 Cyclohexadienyl anion intermediate (a) + .. .. H p-Nitroanisole Dow process : Cl OH 300°C  High pressure + Aq.NaOH + NaCl (via benzyne mechanism) Presence of deactivating group in ortho and para position makes the nucleophilic substitution easier. Reactivity Order : (Towards nucleophilic substitution) Cl NO2 Cl NO2 > NO2 Cl Cl NO2 > NO2 > NO2 ALKYL HALIDES & ARYL HALIDES Br (b) NH 2 liq. NH 3  + KNH 2 Strong base + KBr low temperature Cl (c) CN Pyridine, 300°C  + CuCN + CuCl high pressure Fitting reaction : Wurtz fitting reaction : Formation of aryl magnesium halide : THF Cl + Mg  MgCl Reduction : X Ni—Al/NaOH  With Chloral : Electrophilic Substitution Reaction : Cl (i) Cl + Cl2 FeCl3  Cl Cl + Cl Cl is o– and p– directing group. Cl Cl + HNO3 (ii) Cl NO2 H2SO4   + NO 2 (iii) (iv) Friedal Craft Reaction : Cl Cl + CH3Cl AlCl3  CH3 Cl + CH3 ALKYL HALIDES & ARYL HALIDES 1. Miscellaneous Reactions : Freons (Polychlorofluoro Alkane) (i) CCl4 + HF SbCl4 CCl3F + HCl (Freon-11) (ii) CCl3F + HF   CCl2F2 + HCl (Freon-1 2) (iii) C2Cl6 + 2HF  C2Cl4F2 + 2HCl (Freon-112) Nomenclature of Freons : Freon is expressed as Freon - cba Where: a – [Number of F-atoms] b – [1 + Number of H–atoms] c – [Number of C-atoms –1] Ex. C2Cl4F2 is expressed as Freon-112 a=2; b=1+0; c = 2 – 1cab = 112  Freon is odourless, non-corrosive, non-toxic gas. It can easily be liquefied hence widely used as refrigerant. 2. Carbon tetrachloride (pyrene) : Preparations & reactions :  CCl4 is stable to heat and its vapours do not catch fire thus it is used as fire extinguisher.  CCl4 used as medicine for elimination of hook worms. 3. Reactions of chloroform :  Purity of chloroform (presence of phosgene) can be tested before use as anaesthetic by treating with aqueous solution of AgNO3 because the presence of COCl2 may cause cardiac failure.  Chloroform is stored in dark colour bottle containing small amount of ethyl alcohol. (It converts phosgene into diethylcarbonate). 4. Summary of Nucleophilic substitution Reactions (SN1 and SN2) R–X= Nuc/ Base Strength methyl 1° 2° 3° Strong/strong SN2 SN2 strong/weak SN2 SN2 E2 SN2 E2 no reaction weak / strong no reaction E2 weak/ weak no reaction n no reaction E2 E2 SN1/E1