4.8 Preparation of Alkyl Halides from Alcohols and Hydrogen Halides ROH + HX  RX + H2O 6

Reaction of Alcohols with Hydrogen Halides ROH + HX  RX + HOH Hydrogen halide reactivity HI HBr HCl HF most reactive least reactive 2

Reaction of Alcohols with Hydrogen Halides ROH + HX  RX + HOH Alcohol reactivity R3COH R2CHOH RCH2OH CH3OH Tertiary Secondary Primary Methanol most reactive least reactive 2

Preparation of Alkyl Halides 25°C (CH3)3COH + HCl (CH3)3CCl + H2O 78-88% OH + HBr 80-100°C Br + H2O 73% 120°C CH3(CH2)5CH2OH + HBr CH3(CH2)5CH2Br + H2O 87-90% 4

Preparation of Alkyl Halides A mixture of sodium bromide and sulfuric acid may be used in place of HBr. NaBr H2SO4 CH3CH2CH2CH2OH CH3CH2CH2CH2Br heat 70-83% 5

4.9 Mechanism of the Reaction of Alcohols with Hydrogen Halides 6

Carbocation C R + The key intermediate in reaction of secondary and tertiary alcohols with hydrogen halides is a carbocation. A carbocation is a cation in which carbon has 6 valence electrons and a positive charge. 7

Carbocation C R + The key intermediate in reaction of secondary and tertiary alcohols with hydrogen halides is a carbocation. The overall reaction mechanism involves three elementary steps; the first two steps lead to the carbocation intermediate, the third step is the conversion of this carbocation to the alkyl halide. 7

Carbocation intermediate is: Example 25°C (CH3)3COH + HCl (CH3)3CCl + H2O tert-Butyl alcohol tert-Butyl chloride Carbocation intermediate is: C H3C CH3 + tert-Butyl cation 9

Step 1: Proton transfer from HCl to tert-butyl alcohol Mechanism Step 1: Proton transfer from HCl to tert-butyl alcohol .. H Cl : .. + (CH3)3C O : H fast, bimolecular H O : + (CH3)3C Cl .. – tert-Butyloxonium ion 9

Step 2: Dissociation of tert-butyloxonium ion Mechanism Step 2: Dissociation of tert-butyloxonium ion (CH3)3C O H : + slow, unimolecular O H : + + (CH3)3C tert-Butyl cation 9

Step 3: Capture of tert-butyl cation by chloride ion. Mechanism Step 3: Capture of tert-butyl cation by chloride ion. Cl : .. – + (CH3)3C + fast, bimolecular (CH3)3C Cl : .. tert-Butyl chloride 9

4.10 Structure, Bonding, and Stability of Carbocations 6

Figure 4.8 Structure of methyl cation. Carbon is sp2 hybridized. All four atoms lie in same plane. 10

Figure 4.8 Structure of methyl cation. Empty 2p orbital. Axis of 2p orbital is perpendicular to plane of atoms. 10

Most carbocations are too unstable to be isolated. + Most carbocations are too unstable to be isolated. When R is an alkyl group, the carbocation is stabilized compared to R = H. 7

Methyl cation least stable Carbocations C H + Methyl cation least stable 7

Ethyl cation (a primary carbocation) is more stable than CH3+ Carbocations H3C + H C H Ethyl cation (a primary carbocation) is more stable than CH3+ 7

Isopropyl cation (a secondary carbocation) is more stable than CH3CH2+ Carbocations H3C + CH3 C H Isopropyl cation (a secondary carbocation) is more stable than CH3CH2+ 7

Carbocations H3C + CH3 C CH3 tert-Butyl cation (a tertiary carbocation) is more stable than (CH3)2CH+ 7

Figure 4.9 Stabilization of carbocations via the inductive effect positively charged carbon pulls electrons in  bonds closer to itself + 18

Figure 4.9 Stabilization of carbocations via the inductive effect  positive charge is "dispersed ", i.e., shared by carbon and the three atoms attached to it    18

Figure 4.9 Stabilization of carbocations via the inductive effect electrons in C—C bonds are more polarizable than those in C—H bonds; therefore, alkyl groups stabilize carbocations better than H.     Electronic effects transmitted through bonds are called "inductive effects." 18

Figure 4.10 Stabilization of carbocations via hyperconjugation electrons in this  bond can be shared by positively charged carbon because the s orbital can overlap with the empty 2p orbital of positively charged carbon + 18

Figure 4.10 Stabilization of carbocations via hyperconjugation electrons in this  bond can be shared by positively charged carbon because the s orbital can overlap with the empty 2p orbital of positively charged carbon   18

Figure 4.10 Stabilization of carbocations via hyperconjugation Notice that an occupied orbital of this type is available when sp3 hybridized carbon is attached to C+, but is not availabe when H is attached to C+. Therefore,alkyl groups stabilize carbocations better than H does.   18

The more stable a carbocation is, the faster it is formed. Carbocations C R + The more stable a carbocation is, the faster it is formed. Reactions involving tertiary carbocations occur at faster rates than those proceeding via secondary carbocations. Reactions involving primary carbocations or CH3+ are rare. 7

Carbocations are Lewis acids (electron-pair acceptors). + Carbocations are Lewis acids (electron-pair acceptors). Carbocations are electrophiles (electron-seekers). Lewis bases (electron-pair donors) exhibit just the opposite behavior. Lewis bases are nucleophiles (nucleus-seekers). 7

Step 3: Capture of tert-butyl cation by chloride ion. Mechanism Step 3: Capture of tert-butyl cation by chloride ion. Cl : .. – + (CH3)3C + fast, bimolecular (CH3)3C Cl : .. tert-Butyl chloride 9

Carbocations Cl : .. – (CH3)3C Cl : .. + (CH3)3C + The last step in the mechanism of the reaction of tert-butyl alcohol with hydrogen chloride is the reaction between an electrophile and a nucleophile. tert-Butyl cation is the electrophile. Chloride ion is the nucleophile. 7

Fig. 4.11 Combination of tert-butyl cation and chloride ion to give tert-butyl chloride nucleophile (Lewis base) + – electrophile (Lewis acid) 16

4.11 Potential Energy Diagrams for Multistep Reactions: The SN1 Mechanism 6

the potential energy diagram for proton transfer from HBr to water Recall... the potential energy diagram for proton transfer from HBr to water   H2O H Br Potential energy H2O + H—Br H2O—H + Br – + Reaction coordinate 22

Extension The potential energy diagram for a multistep mechanism is simply a collection of the potential energy diagrams for the individual steps. Consider the mechanism for the reaction of tert-butyl alcohol with HCl. (CH3)3COH + HCl (CH3)3CCl + H2O 25°C 9

Step 1: Proton transfer from HCl to tert-butyl alcohol Mechanism Step 1: Proton transfer from HCl to tert-butyl alcohol .. H Cl : .. + (CH3)3C O : H fast, bimolecular H O : + (CH3)3C Cl .. – tert-butyloxonium ion 9

Step 2: Dissociation of tert-butyloxonium ion Mechanism Step 2: Dissociation of tert-butyloxonium ion (CH3)3C O H : + slow, unimolecular O H : + + (CH3)3C tert-Butyl cation 9

Step 3: Capture of tert-butyl cation by chloride ion. Mechanism Step 3: Capture of tert-butyl cation by chloride ion. Cl : .. – + (CH3)3C + fast, bimolecular (CH3)3C Cl : .. tert-Butyl chloride 9

carbocation formation carbocation capture proton transfer ROH2 + ROH RX 21

carbocation formation carbocation capture (CH3)3C O H Cl + – R+ ROH2 + ROH RX 21

(CH3)3C + O H carbocation capture R+ proton transfer ROH2 + ROH RX 21

carbocation formation (CH3)3C + Cl – carbocation formation R+ proton transfer ROH2 + ROH RX 21

The mechanism just described is an example of an SN1 process. Mechanistic notation The mechanism just described is an example of an SN1 process. SN1 stands for substitution-nucleophilic- unimolecular. The molecularity of the rate-determining step defines the molecularity of the overall reaction. 9

Mechanistic notation The molecularity of the rate-determining step defines the molecularity of the overall reaction. (CH3)3C + O H Rate-determining step is unimolecular dissociation of alkyloxonium ion. 9

4.12 Effect of Alcohol Structure on Reaction Rate 6

slow step is: ROH2+  R+ + H2O The more stable the carbocation, the faster it is formed. Tertiary carbocations are more stable than secondary, which are more stable than primary, which are more stable than methyl. Tertiary alcohols react faster than secondary, which react faster than primary, which react faster than methanol. 22

Hammond's Postulate If two succeeding states (such as a transition state and an unstable intermediate) are similar in energy, they are similar in structure. Hammond's postulate permits us to infer the structure of something we can't study (transition state) from something we can study (reactive intermediate). 23

carbocation formation carbocation capture proton transfer ROH2 + ROH RX 21

carbocation formation Rate is governed by energy of this transition state. Infer structure of this transition state from structure of state of closest energy; in this case the nearest state is the carbocation. carbocation capture R+ proton transfer ROH2 + ROH RX 21

4. 13 Reaction of Primary Alcohols with Hydrogen Halides 4.13 Reaction of Primary Alcohols with Hydrogen Halides. The SN2 Mechanism 6

Preparation of Alkyl Halides 25°C (CH3)3COH + HCl (CH3)3CCl + H2O 78-88% OH + HBr 80-100°C Br + H2O 73% 120°C CH3(CH2)5CH2OH + HBr CH3(CH2)5CH2Br + H2O 87-90% 4

Preparation of Alkyl Halides Primary carbocations are too high in energy to allow SN1 mechanism. Yet, primary alcohols are converted to alkyl halides. Primary alcohols react by a mechanism called SN2 (substitution-nucleophilic-bimolecular). 120°C CH3(CH2)5CH2OH + HBr CH3(CH2)5CH2Br + H2O 87-90% 4

Two-step mechanism for conversion of alcohols to alkyl halides: The SN2 Mechanism Two-step mechanism for conversion of alcohols to alkyl halides: (1) proton transfer to alcohol to form alkyloxonium ion (2) bimolecular displacement of water from alkyloxonium ion by halide 27

Example 120°C CH3(CH2)5CH2OH + HBr CH3(CH2)5CH2Br + H2O 4

Step 1: Proton transfer from HBr to 1-heptanol Mechanism Step 1: Proton transfer from HBr to 1-heptanol O CH3(CH2)5CH2 .. .. : + H Br : .. H fast, bimolecular H Br : .. – + CH3(CH2)5CH2 O : + H Heptyloxonium ion 9

Step 2: Reaction of alkyloxonium ion with bromide ion. Mechanism Step 2: Reaction of alkyloxonium ion with bromide ion. H O : + CH3(CH2)5CH2 Br : .. – + slow, bimolecular O H : Br : .. CH3(CH2)5CH2 + 1-Bromoheptane 9

CH2 OH2 + Br – CH3(CH2)4 CH2 proton transfer ROH ROH2 + RX 31

4.14 Other Methods for Converting Alcohols to Alkyl Halides 6

Phosphorus tribromide PBr3 + 3ROH  3RBr + H3PO3 Reagents for ROH to RX Thionyl chloride SOCl2 + ROH  RCl + HCl + SO2 Phosphorus tribromide PBr3 + 3ROH  3RBr + H3PO3 33

(pyridine often used instead of K2CO3) Examples SOCl2 CH3CH(CH2)5CH3 CH3CH(CH2)5CH3 K2CO3 Cl OH (81%) (pyridine often used instead of K2CO3) PBr3 (CH3)2CHCH2OH (CH3)2CHCH2Br (55-60%) 34