CHAPTER 7 HALOALKANES1
INTRODUCTION▪ Haloalkanes are compounds in which a halogen atom (F, Cl, Br or I) replaces a H atom of an alkane.▪ General formula: CnH2n + 1X or RXwhere X= Cl, Br, F, I▪ Also known as alkyl halides7.1 INTRODUCTION TO HALOALKANES 2
CLASSIFICATION OF HALOALKANESDepending on the number of alkyl groupsattached to the C atom bonded to the halogen, known as α-carbonMETHYL HALIDEHalogen is bonded to methyl groupPRIMARY HALOALKANE1 alky group bonded to α-carbonSECONDARY HALOALKANE2 alkyl groups bonded to α-carbonTERTIARY HALOALKANE3 alkyl groups bonded to α-carbonR CHHXR CHRX3
EXAMPLE : Methyl halide1ᵒ haloalkane2ᵒ haloalkane3ᵒ haloalkane4
NOMENCLATUREExample:chloroethane 2-bromopropane2-chloro-3-methylpentane 3-chloro-2-methylpentaneCH3CH2ClCH CH3CH3Br A haloalkane is named as an alkane with halogen as substituent. The name is based on the longest carbon chain. To name the halogen substituent, use prefixes fluoro-, chloro-, bromo- or iodo-.5
NOMENCLATURE If 2 or more substituents (halogen or alkyl groups) are present, find the parent carbon chain. Apply other rules for nomenclaturei. Number the chain starting at the end nearest the first substituent either alkyl or halogen.ii. Name and number the substituent.ii. Alphabetise the substituents.2-chloro-4-methylpentane 1-chloro-2-fluoroethaneExample:6
NOMENCLATUREExample:2-chloro-3-methylpentane 3-chloro-2-methylpentane7
2-bromo-3,4-dimethylheptane2,3-dichloro-4-methylhexane2-bromo-4-chloro-3-methylpentane123Exercise: Give IUPAC names for the following compounds: 8
3,5-dibromo-4-chlorooctaneiodocyclohexane2-chloro-1,1-dimethylcyclopentane1-iodo-3-methylbutane45679
▪ Common names of haloalkanes are constructed by naming the alkyl groupand then the halide alkyl halide.▪ Common names are useful only for simple alkyl halides.methyl bromide n-butyl chloride isopropyl bromideCOMMON NAMECH3BrCommon nameIUPAC namebromomethane 1-chlorobutane 2-bromobutaneExample:10
Types of reactions Nucleophilic substitution reactionElimination reactionGeneral equation:Preparation of alkenes (Chapter 5)7.2 CHEMICAL PROPERTIES OF HALOALKANES 11
Nucleophilic Substitution Reactions of R−XWith aqueous solution of NaOHR–X + NaOH(aq) R−OH + NaXR–X + excessNH3(1ᵒamine)R–NH2 +HXWith alcohol (ROH)R–X + ROH R−OR + HXWith H2OR–X + H2O R−OH +X− +H3O+With KCN in alcohol, refluxR– X + KCN R−CN + KX ROHR–X + −OR R−OR + X−R–X + CH3COO− CH3COOR + X −With CH3COO−With excess NH3With RO−12
δ+ δPolar bond13▪ Halogens have electronegativities significantly greater than C atom.▪ Consequently, the C – X bond is polarized.▪ The electrophilic C atom is susceptible to nucleophilic attack.▪ Thus, haloalkanes tend to undergo nucleophilic substitution reaction involving the replacement of the halogen by a nucleophile (Nu:-).▪ A nucleophile is either an anion or a neutral molecule with lone pair at the central atom.R – X + :Nu− R – Nu + X−General equation:13
RX + NaOH (aq) ROH + NaX+ NaOH (aq) + NaCl+ NaOH(aq) + NaBrEXAMPLE :1. REACTION OF HALOALKANE WITH AQUEOUS NAOH▪ When haloalkane is treated with aqueous NaOH or KOH, halogen is replacedby −OH to produce alcohol.General reaction:12 CH3CH2Cl CH3CH2OH14
Example:R – X + excess NH3 R – NH2 + HX+ excess NH3 + HBrΔethylamine (1o amine )+ excess NH3Δ+ HI2. REACTION OF HALOALKANE WITH EXCESS NH3▪ Haloalkane is heated under reflux with excess ammonia solution▪ Halogen is replaced by −NH2to produce 1° amine12General reaction: ΔCH3CH2Br CH3CH2NH215
RX + 2H2O ROH + H3O+ + X−+ 2 H2O+ 2H2O + H3O+ + Br−EXAMPLE :3. REACTION OF HALOALKANE WITH WATER (HYDROLYSIS)▪ Haloalkane reacts with water, H2O to produce alcohol.▪ Favoured by 3° haloalkane via SN1 mechanism.General equation:12+ H3O+ + Br−16
4. REACTION OF HALOALKANE WITH ALCOHOL (ALCOHOLYSIS)General reaction: RX + R’OH ROR’ + HXEXAMPLE : 1 CH3CH2Cl + CH3CH2OH CH3CH2OCH2CH3+ HCl▪ Haloalkane is reacted with alcohol▪ Halogen is replaced by −OR to produce ether17
▪ Haloalkane is heated under reflux with solution of potassium or sodiumcyanide in alcohol.▪ Halogen is replaced by −CN to produce nitrile compound.RX + KCN RCN + KXΔalcohol▪ In this reaction, number of C atom in the product is increased by one(lengthening the chain)5. REACTION OF HALOALKANE WITH ALCOHOLIC KCN @ NaCNGeneral reaction:18
EXAMPLE : 12CH3CH2Br + KCN CH3CH2CN + KBr19
6. REACTION OF HALOALKANE WITH SODIUM OR POTASSIUM ALKOXIDE ▪ When haloalkane reacts with potassium or sodium alkoxide, halogen is replaceby −OR to produce ether.▪ Normally occur to 1° haloalkane. General reaction:RX + R’O- ROR’ + XEXAMPLE : 1 CH3CH2CH2Br + CH3CH2ONa CH3CH2CH2OCH2CH3 + NaBr2 CH3CH2Cl + CH3O- CH3CH2OCH3 + Cl20
▪ When haloalkane reacts with sodium or potassium carboxylate, halogen isreplaced by RCOO−to produce esterRX + R’COO- R’COOR + X7. REACTION OF HALOALKANE WITH SODIUM OR POTASSIUM CARBOXYLATEGeneral reaction:EXAMPLE : 1 CH3CH2Cl21
Draw the structure of the product formed when 1-bromopropane reacts with the following reagents respectively:(i) Ammonia(ii) Methanol(iii) Sodium cyanide(iv) WaterEXERCISE(ii) CH3 OH(iii) NaCN,alcohol(iv) H2O(i) NH3 (excess)ANSWER22
2 types of mechanism for nucleophilic substitution reaction:▪ Unimolecular Nucleophilic Substitution Reaction, SN1 ▪ Bimolecular Nucleophilic Substitution Reaction, SN2The mechanism involved in nucleophilic substitution depends on:▪ the structure of the haloalkane ▪ strength of nucleophileMECHANISM OF REACTION OF R−XNUCLEOPHILIC SUBSTITUTION23
▪ First order reaction▪ Rate equation : ▪ Rate of reaction depends only on the concentration of haloalkane, [haloalkane]▪ Involved formation of carbocation▪ Favoured by 3° RX and 1° RX with large (bulky) alkyl groups▪ Mechanism involves TWO STEPS:rate = k [haloalkane]UNIMOLECULAR NUCLEOPHILIC SUBSTITUTION, SN1STEP 1: Formation of the carbocationSTEP 2: Nucleophilic attack24
GENERAL MECHANISM FOR SN1:Step 1 : Formation of carbocation+ + X−slow3ᵒ carbocationδ+ δHeterolytic cleavagerate determining stepStep 2 : Nucleophilic attack+3ᵒ carbocation:Nu + −fast25
EXAMPLE 1: Write a complete mechanism for the reaction :+ 2H2O(aq) + H3O+ + Br−Step 1 : Formation of carbocationδ+ δ- slowrate determining stepStep 2 : Nucleophilic attack+fast+ Br −26
Step 3 : Deprotonation +fast+ H3O+27
, , ,▪ For RX with the same halogen, reactivity of haloalkanes towards SN1 reaction follows the stability of carbocations.Methyl halide primary secondary tertiaryRELATIVE REACTIVITIES OF 1ᵒ, 2ᵒ AND 3ᵒ R-X OF SN1 methyl primary secondary tertiaryIncreasing reactivity of haloalkanes towards SN1 reactionIncreasing stability of carbocation28
▪ 3° RX undergo SN1 reactions the most rapidly because 3° carbocation is themost stable.+ + X−3ᵒ 3ᵒ haloalkane carbocation▪ Factor determines reactivity of RX for SN1 reaction is the stability of thecarbocation. Alky group is electron-donating group. More alky groups attached to the positively charged carbon will stabilise the carbocations through inductive effect. Thus, 3° carbocation is the most stable compared to 2o and 1ocarbocations.29
▪ Second order reaction▪ Rate equation : Rate = k [haloalkane] [nucleophile]▪ Rate of reaction depends on the concentration of haloalkane, [haloalkane] andconcentration of nucleophile [:Nu−]▪ Involved formation of transition state.▪ Favoured by methyl halide and 1° RX▪ Mechanism involves only ONE STEP:BIMOLECULAR NUCLEOPHILIC SUBSTITUTION, SN2The processes of bond breaking and bond forming occur simultaneouslyas one bond is forming, the other bond is breaking30
− HO+ NaBrConsider the following reaction :1° RXNucleophile+ NaOH(aq)EXAMPLE:CH3CH2Cl CH3CH2OH31
+ Br −δ+ δTransition state(i) −OH ion (nucleophile) attacks the electrophilic α−carbon atom (ii)To minimise repulsions between RX and OH−, the −OH attacks the è deficient C atom at the side opposite to the halogen.(iii) When the C−OH bond begins to form the C−Br bond becomes weakenand finally broken. (iv) Br is replaced by OH and the configuration of product is inverted.HO–δ- δSlowRate-determining stepfast+ Br CH -3CH2Cl + -OH CH3CH2OHSN2 Mechanism:Chemical Equation: 32
▪ All SN2 reactions proceed with backside attack by the nucleophile, hence theproduct formed has inverse configuration.STEREOCHEMISTRY IN SN2The substitution reaction turns the tetrahedron of the carbon atom inside out, likean umbrella turned inside out when caught in a strong windδ+ δHO– + Br −33
▪ For RX with the same halogen Factor that determines the order of reactivity in SN2 is the steric effect. If steric effect increases, reactivity of haloalkane will decrease.Relative Reactivities of 1ᵒ, 2ᵒ and 3ᵒ RX with SN2,, ,tertiary secondary primary methylhalideCHRC R XRRR X CHHR XIncreasing reactivity towards SN 234
▪ Is one in which the rate of reaction depends on the spatial arrangement of the group attached to, or near to the reaction siteof the molecule▪ Steric hindrance caused by bulky R groups makes :Nu− attack from the back side more difficult.STERIC EFFECT IN SN235
3ᵒ R-X 3o haloalkanes do NOT favour SN2 reactionor 3o haloalkanes is the least reactivetowards SN2 because the high steric effect/hindrance which makes nucleophilic attackdifficult. The greater the number of alkyl group or the larger the size of alkyl group attached to the carbon, steric effect /hindrance increases, causing the nucleophilic attack from the backside more difficult, thus slowing the rate. Methyl halide(chloromethane) In contrast, the -carbon in methyl halide is the least hindered. Methyl halides can react the most rapidly in SN2.site of reactionδ+ δδ+ δsite of reaction:Nu −:Nu−36
Exceptional cases 1o haloalkanes are not able to form stable carbocation. Therefore, generally 1o haloalkanes favour SN2. However, in some cases of 1o haloalkane such as 1-bromo-2-2-dimethylpropane (neopentyl bromide) is 1o haloalkane, the presence of bulkyt-butyl group makes the nucleophilic attack more difficult. Thus, the hydrolysis of 1-bromo-2-2-dimethylpropane occurs by SN1 with rearrangement of carbocation. The 1o carbocation rearranges in order to form 3o carbocation which is more stable. CCH3CH3H CH2Br 3C- + carbon37
+ NaOH + NaBrslow1o carbocation(less stable)EXAMPLE 2: Write a mechanism for the following reaction :Step 1 : Formation of carbocation+ Br−38
1o carbocation(less stable)1,2-methyl shiftRearrangement of carbocation3o carbocation(more stable)Step 2 : Nucleophilic attack on carbocation+ −OHfast39
STRENGTH OF NUCLEOPHILE ▪ Is a measure of how fast a nucleophile displaces aleaving group.▪ The SN2 reaction depends on both the concentration ofnucleophile and the identity of nucleophile.▪ A negatively charged nucleophile is generally stronger ormore reactive than a similar neutral nucleophile.− OH> H2OCH3O− > CH3OH▪ Strong nucleophile in high concentration favours SN2reactionsSome Common NucleophilesStrong Nu:-− OH, RO−, − CNWeak Nu:-Moderate:-H2O, ROHRCOOHNH3, RCOO−40
SN1Meaning:Substitution Nucleophilic unimolecularFirst order reaction Rate = k [RX]Nucleophile:Weak nucleophile (normally neutral) e.g. H2OOrder of reactivityMethyl halides <1°< 2°< 3°SN2Meaning:Substitution Nucleophilic bimolecularSecond order reaction Rate = k [RX] [ Nu:−]Nucleophile: Strong Nucleophile e.g. OH−Order of reactivity:3°< 2° < 1° < methyl halidesSUMMARY OF SN1 AND SN2 REACTIONS 41
R−X + Mg RMg−Xdry etherTHE USE OF HALOALKANESAr−X + Mg ArMg−Xdry ether▪ Used in preparation of organometallic compounde.g. Grignard reagents (alkyl or aryl magnesium halides)▪ Grignard reagent is prepared by the reaction of an organic halide with Mgin dry ether solvent, in which the C—X bond is replaced by C—Mg bond inthe reaction.General equation:▪ Grignard reagent contains very polar C—Mg bond and useful in thesynthesis of alkanes, alcohols and carboxylic acids.C—Mg- +42
USES OF RMgX1° alcoholalkane2° alcoholmethanalaldehydePreparation of AlkanePreparation of 1° AlcoholPreparation of 2° Alcohol43
USES OF RMgX3° alcoholPreparation of 3° Alcoholcarboxylic acidPreparation of Carboxylic Acidketonecarbon dioxide44
1. PREPARATION OF ALKANESExample : δ −δ + 12▪ Acidic hydrolysis of Grignard reagent gives alkane.Mg(OH)ClCH2MgClH3O+CH3+methylcyclohexaneCCH3CH3H3C MgBr H3O+CCH3CH3H3C H + Mg(OH)Br2-methylpropane45
PREPARATION OF 1O ALCOHOLS▪ Addition of Grignard reagent to methanal followed by hydrolysisproduces a primary alcohol.Example : 1° alcohol2. PREPARATION OF ALCOHOLS 46
PREPARATION OF 2O ALCOHOLS▪ Addition of Grignard reagent to aldehyde followed by hydrolysisproduces a secondary alcohol.Example : 2° alcohol47
1PREPARATION OF 3O ALCOHOLS▪ Addition of Grignard reagent to ketone followed by hydrolysisproduces a tertiary alcohol.2Example: 3° alcohol3° alcohol CCH3OCCH3OHCH2CH3+ Mg(OH)Bri. CH3CH2MgBrii. H3O+48
PREPARATION OF CARBOXYLIC ACID▪ Reaction of Grignard reagent with carbon dioxide followed by hydrolysisproduces a carboxylic acid.49
Example: 12CH CHMgBr 3CH3i. CO2ii. H3O+CH3CHCOOH CH3MgCl+ O C OCO- +O MgClH3O+ C O OH+ Mg(OH)Cl50