CHAPTER FOUR Alcohols and Alkyl Halides R R O:+H-A O—H Acid kyloxonium ion Conjugate base We shall see that several important reactions of alcohols involve strong acids either as reagents or as catalysts to increase the rate of reaction. In all these reactions the first step is formation of an alkyloxonium ion by proton transfer from the acid to the oxygen of the alcohol PROBLEM 4.9 Write an equation transfer from hydrogen chloride to tert-butyl alcohol. Use curved arro k electron movement, and identify the acid, base, conjugate acid, and PROBLEM 4.10 Is the equilibrium constant for proton transfer from hydrogen chloride to tert-butyl alcohol greater than 1 or less than 1? Alkyl halides are neither very acidic nor very basic and are absent from Table 4.2 In general, compounds, including alkyl halides, in which all the protons are bonded to carbon are exceedingly weak acids--too weak to be included in the table 4.7 ACID-BASE REACTIONS: A MECHANISM FOR PROTON TRANSFER Potential energy diagrams of the type used in Chapter 3 to describe conformational processes can also help us understand more about chemical reactions. Consider the trans fer of a proton from hydrogen bromide to water Br-H+:0:、:Br:+H-O: A potential energy diagram for this reaction is shown in Figure 4.6. Because the transfer of a proton from hydrogen bromide to water is exothermic, the products are placed lower in energy than the reactants. The diagram depicts the reaction as occurring in a single elementary step. An elementary step is one that involves only one transition state. A reaction can proceed by way of a single elementary step, in which case it is described as a concerted reaction, or by a series of elementary steps. In the case of pro- ton transfer from hydrogen bromide to water, breaking of the H-Br bond and making of the H2o-H bond occur "in concert with each other. The species present at the transition state is not a stable structure and cannot be isolated or examined directly. Its structure is assumed to be one in which the proton being transferred is partially bonded to both bromine and oxygen simultaneously, although not necessarily to the same extent. ate structures represe partial bonds, that is, bond in the process of being made or broke Back Forward Main Menu Study Guide ToC Student OLC MHHE Website
We shall see that several important reactions of alcohols involve strong acids either as reagents or as catalysts to increase the rate of reaction. In all these reactions the first step is formation of an alkyloxonium ion by proton transfer from the acid to the oxygen of the alcohol. PROBLEM 4.9 Write an equation for proton transfer from hydrogen chloride to tert-butyl alcohol. Use curved arrows to track electron movement, and identify the acid, base, conjugate acid, and conjugate base. PROBLEM 4.10 Is the equilibrium constant for proton transfer from hydrogen chloride to tert-butyl alcohol greater than 1 or less than 1? Alkyl halides are neither very acidic nor very basic and are absent from Table 4.2. In general, compounds, including alkyl halides, in which all the protons are bonded to carbon are exceedingly weak acids—too weak to be included in the table. 4.7 ACID–BASE REACTIONS: A MECHANISM FOR PROTON TRANSFER Potential energy diagrams of the type used in Chapter 3 to describe conformational processes can also help us understand more about chemical reactions. Consider the transfer of a proton from hydrogen bromide to water: A potential energy diagram for this reaction is shown in Figure 4.6. Because the transfer of a proton from hydrogen bromide to water is exothermic, the products are placed lower in energy than the reactants. The diagram depicts the reaction as occurring in a single elementary step. An elementary step is one that involves only one transition state. A reaction can proceed by way of a single elementary step, in which case it is described as a concerted reaction, or by a series of elementary steps. In the case of proton transfer from hydrogen bromide to water, breaking of the H±Br bond and making of the H2O ±H bond occur “in concert” with each other. The species present at the transition state is not a stable structure and cannot be isolated or examined directly. Its structure is assumed to be one in which the proton being transferred is partially bonded to both bromine and oxygen simultaneously, although not necessarily to the same extent. Br H O H H Br H H H O H H H Br O R H O Alcohol H A Acid A Alkyloxonium ion Conjugate base R H O H 136 CHAPTER FOUR Alcohols and Alkyl Halides Dashed lines in transitionstate structures represent partial bonds, that is, bonds in the process of being made or broken. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
4.8 Preparation of Alkyl Halides From Alcohols and Hydrogen Halides H.O-H-B Transition state FIGURE 4.6 Energy diagram for concerted bi molecular proton transfer from hydrogen bromide to H,0+ H-Br Reaction coordinate- The molecularity of an elementary step is given by the number of species that undergo a chemical change in that step. The elementary step HBr H0= Br H3o is bimolecular because it involves one molecule of hydrogen bromide and one mole- cule of water PROBLEM 4.11 Represent the structure of the transition state for proton trans- fer from hydrogen chloride to tert-butyl alcohol Proton transfer from hydrogen bromide to water and alcohols ranks among the The 1967 Nobel Prize in most rapid chemical processes and occurs almost as fast as the molecules collide with emistry was shared by one another. Thus the height of the energy barrier separating reactants and products, the Manfred Eigen, a german activation energy for proton transfer, must be quite low. novel methods for measu The concerted nature of proton transfer contributes to its rapid rate. The energy ing the rate cost of breaking the H-Br bond is partially offset by the energy released in making the reactions such as prc H2O-H bond. Thus, the activation energy is far less than it would be for a hypothet ical stepwise process involving an initial, unassisted ionization of the H-Br bond, fol lowed by a combination of the resulting H with water 4. 8 PREPARATION OF ALKYL HALIDES FROM ALCOHOLS AND HY DROGEN HALIDES Much of what organic chemists do is directed toward practical goals. Chemists in the pharmaceutical industry synthesize new compounds as potential drugs for the treatment of disease. Agricultural chemicals designed to increase crop yields include organic com- pounds used for weed control, insecticides, and fungicides. Among the"building block molecules used as starting materials to prepare new substances, alcohols and alkyl halides are especially valuable The procedures to be described in the remainder of this chapter use either an alkane or an alcohol as the starting material for preparing an alkyl halide. By knowing how to Back Forward Main Menu Study Guide ToC Student OLC MHHE Website
The molecularity of an elementary step is given by the number of species that undergo a chemical change in that step. The elementary step HBr H2O BA Br H3O is bimolecular because it involves one molecule of hydrogen bromide and one molecule of water. PROBLEM 4.11 Represent the structure of the transition state for proton transfer from hydrogen chloride to tert-butyl alcohol. Proton transfer from hydrogen bromide to water and alcohols ranks among the most rapid chemical processes and occurs almost as fast as the molecules collide with one another. Thus the height of the energy barrier separating reactants and products, the activation energy for proton transfer, must be quite low. The concerted nature of proton transfer contributes to its rapid rate. The energy cost of breaking the H±Br bond is partially offset by the energy released in making the H2O ±H bond. Thus, the activation energy is far less than it would be for a hypothetical stepwise process involving an initial, unassisted ionization of the H±Br bond, followed by a combination of the resulting H with water. 4.8 PREPARATION OF ALKYL HALIDES FROM ALCOHOLS AND HYDROGEN HALIDES Much of what organic chemists do is directed toward practical goals. Chemists in the pharmaceutical industry synthesize new compounds as potential drugs for the treatment of disease. Agricultural chemicals designed to increase crop yields include organic compounds used for weed control, insecticides, and fungicides. Among the “building block” molecules used as starting materials to prepare new substances, alcohols and alkyl halides are especially valuable. The procedures to be described in the remainder of this chapter use either an alkane or an alcohol as the starting material for preparing an alkyl halide. By knowing how to 4.8 Preparation of Alkyl Halides From Alcohols and Hydrogen Halides 137 Potential energy Transition state Reaction coordinate H2O---H---Br H2O H–Br H3O Br Eact The 1967 Nobel Prize in chemistry was shared by Manfred Eigen, a German chemist who developed novel methods for measuring the rates of very fast reactions such as proton transfers. FIGURE 4.6 Energy diagram for concerted bimolecular proton transfer from hydrogen bromide to water. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER FOUR Alcohols and Alkyl Halides prepare alkyl halides, we can better appreciate the material in later chapters, where alkyl halides figure prominently in key chemical transformations. The preparation of alkyl halides also serves as a focal point to develop the principles of reaction mechanisms We'll begin with the preparation of alkyl halides from alcohols by reaction with hydro- gen halides R一OH+H一X R一X+H-OH Alcohol Hydrogen halide Alkyl halide Water The order of reactivity of the hydrogen halides parallels their acidity: HI HBr HCI>> HF. Hydrogen iodide is used infrequently, however, and the reaction of alcohols with hydrogen fluoride is not a useful method for the preparation of alkyl Among the various classes of alcohols, tertiary alcohols are observed to be the most reactive and primary alcohols the least reactive toward hydrogen halides CH3OH RCH,OH R,CHOH R3 COH Primary Least reactive Most reactive Tertiary alcohols are converted to alkyl chlorides in high yield within minutes on reaction with hydrogen chloride at room temperature and below (CH3)3COH+ (CH3)3CCI +ho 2-Met propanol Hydrogen chloride 2-Chloro-2-methylpropane (tert-butyl chloride)(78-88%) he efficiency of a synthe Secondary and primary alcohols do not react with hydrogen chloride at rate ansted as a percenmally enough to make the preparation of the corresponding alkyl chlorides a method of vated temperatures are required in order to increase the rate of reaction en then eld, tical value. Therefore, the more reactive hydrogen HBr is use uct that could be formed if OH to any products other than those given in the equation Cyclohexanol Hydrogen bromide Bromocyclohexane(73%) Water 1-Heptano Hydrogen I-Bromoheptane The same kind of transformation may be carried out by heating an alcohol with sodium bromide and sulfuric acid CH3CH,CH,CH,OH CH CHCHCH 1-Butanol 1-Bromobutane(70-83%) Back Forward Main Menu Study Guide ToC Student OLC MHHE Website
prepare alkyl halides, we can better appreciate the material in later chapters, where alkyl halides figure prominently in key chemical transformations. The preparation of alkyl halides also serves as a focal point to develop the principles of reaction mechanisms. We’ll begin with the preparation of alkyl halides from alcohols by reaction with hydrogen halides. The order of reactivity of the hydrogen halides parallels their acidity: HI HBr HCl HF. Hydrogen iodide is used infrequently, however, and the reaction of alcohols with hydrogen fluoride is not a useful method for the preparation of alkyl fluorides. Among the various classes of alcohols, tertiary alcohols are observed to be the most reactive and primary alcohols the least reactive. Tertiary alcohols are converted to alkyl chlorides in high yield within minutes on reaction with hydrogen chloride at room temperature and below. Secondary and primary alcohols do not react with hydrogen chloride at rates fast enough to make the preparation of the corresponding alkyl chlorides a method of practical value. Therefore, the more reactive hydrogen halide HBr is used; even then, elevated temperatures are required in order to increase the rate of reaction. The same kind of transformation may be carried out by heating an alcohol with sodium bromide and sulfuric acid. CH3CH2CH2CH2OH 1-Butanol (n-butyl alcohol) CH3CH2CH2CH2Br 1-Bromobutane (70–83%) (n-butyl bromide) NaBr, H2SO4 heat H2O Water Br Bromocyclohexane (73%) 80–100°C HBr Hydrogen bromide OH Cyclohexanol Water CH3(CH2)5CH2Br H2O 1-Bromoheptane (87–90%) HBr Hydrogen bromide CH3(CH2)5CH2OH 1-Heptanol 120°C (CH3)3COH 2-Methyl-2-propanol (tert-butyl alcohol) HCl Hydrogen chloride (CH3)3CCl 2-Chloro-2-methylpropane (tert-butyl chloride) (78–88%) H2O Water 25°C Increasing reactivity of alcohols toward hydrogen halides CH3OH Methyl Least reactive RCH2OH Primary R2CHOH Secondary R3COH Tertiary Most reactive R±OH Alcohol H±X Hydrogen halide R±X Alkyl halide H±OH Water 138 CHAPTER FOUR Alcohols and Alkyl Halides The efficiency of a synthetic transformation is normally expressed as a percent yield, or percentage of the theoretical yield. Theoretical yield is the amount of product that could be formed if the reaction proceeded to completion and did not lead to any products other than those given in the equation. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
1.9 Mechanism of the Reaction of Alcohols With Hydrogen Halides We'll often find it convenient to write chemical equations in the abbreviated form shown here, in which reagents, especially inorganic ones, are not included in the body of the equation but instead are indicated over the arrow. Inorganic products-in this case, water-are usually omitted. These simplifications focus our attention on the organic reac- tant and its functional group transformation PROBLEM 4.12 Write chemical equations for the reaction that takes place between each of the following pairs of reactants (a)2-Butanol and hydrogen bromide (b)3-Ethyl-3-pentanol and hydrogen chloride (c)1-Tetradecanol and hydrogen bromide SAMPLE SOLUTION (a)An alcohol and a hydrogen halide react to form an alkyl halide and water. In this case 2-bromobutane was isolated in 73% yield CH3CHCH2 CH3 HBr ->CH3CHCH2 CH3 H2O 2-Butanol Hydrogen bromide 2-Bromobutane Water 4.9 MECHANISM OF THE REACTION OF ALCOHOLS WITH HYDROGEN HALIDES chlorine or bromine, replaces a hydroxyl group as a substituent on carbon. Calling the reaction a substitution tells us the relationship between the organic reactant and its prod- uct but does not reveal the mechanism. In developing a mechanistic picture for a par ticular reaction, we combine some basic principles of chemical reactivity with experi mental observations to deduce the most likely sequence of elementary steps Consider the reaction of tert-butyl alcohol with hydrogen chloride: (CH3)3COH HCl ->(CH3)3CCl H,O The generally accepted mechanism for this reaction is presented as a series of three ele mentary steps in Figure 4.7. We say"generally accepted"because a reaction mechanism can never be proved to be correct. A mechanism is our best present assessment of how a reaction proceeds and must account for all experimental observations. If new experi mental data appear that conflict with the mechanism, the mechanism must be modified to accommodate them. If the new data are consistent with the proposed mechanism, our confidence grows that it is likely to be correct We already know about step I of the mechanism outlined in Figure 4.7; it is an If you have not already writ- example of a Bronsted acid-base reaction of the type discussed in Section 4.6 and formed ten out the solutions to the basis of Problems 4.9 through 4.11 Problems 4.9 to 4.11, you should do so now Steps 2 and 3, however, are new to us. Step 2 involves dissociation of an alky loxonium ion to a molecule of water and a carbocation, a species that contains a posi- tively charged carbon. In step 3, this carbocation reacts with chloride ion to yield tert- butyl chloride. Both the alkyloxonium ion and the carbocation are intermediates in the reaction. They are not isolated, but are form d consumed in another dur- ing the passage of reactants to products. If we add the equations for steps 1 through 3 together, the equation for the overall process results. A valid reaction mechanism must Back Forward Main Menu Study Guide ToC Student OLC MHHE Website
We’ll often find it convenient to write chemical equations in the abbreviated form shown here, in which reagents, especially inorganic ones, are not included in the body of the equation but instead are indicated over the arrow. Inorganic products—in this case, water—are usually omitted. These simplifications focus our attention on the organic reactant and its functional group transformation. PROBLEM 4.12 Write chemical equations for the reaction that takes place between each of the following pairs of reactants: (a) 2-Butanol and hydrogen bromide (b) 3-Ethyl-3-pentanol and hydrogen chloride (c) 1-Tetradecanol and hydrogen bromide SAMPLE SOLUTION (a) An alcohol and a hydrogen halide react to form an alkyl halide and water. In this case 2-bromobutane was isolated in 73% yield. 4.9 MECHANISM OF THE REACTION OF ALCOHOLS WITH HYDROGEN HALIDES The reaction of an alcohol with a hydrogen halide is a substitution. A halogen, usually chlorine or bromine, replaces a hydroxyl group as a substituent on carbon. Calling the reaction a substitution tells us the relationship between the organic reactant and its product but does not reveal the mechanism. In developing a mechanistic picture for a particular reaction, we combine some basic principles of chemical reactivity with experimental observations to deduce the most likely sequence of elementary steps. Consider the reaction of tert-butyl alcohol with hydrogen chloride: The generally accepted mechanism for this reaction is presented as a series of three elementary steps in Figure 4.7. We say “generally accepted” because a reaction mechanism can never be proved to be correct. A mechanism is our best present assessment of how a reaction proceeds and must account for all experimental observations. If new experimental data appear that conflict with the mechanism, the mechanism must be modified to accommodate them. If the new data are consistent with the proposed mechanism, our confidence grows that it is likely to be correct. We already know about step 1 of the mechanism outlined in Figure 4.7; it is an example of a Brønsted acid–base reaction of the type discussed in Section 4.6 and formed the basis of Problems 4.9 through 4.11. Steps 2 and 3, however, are new to us. Step 2 involves dissociation of an alkyloxonium ion to a molecule of water and a carbocation, a species that contains a positively charged carbon. In step 3, this carbocation reacts with chloride ion to yield tertbutyl chloride. Both the alkyloxonium ion and the carbocation are intermediates in the reaction. They are not isolated, but are formed in one step and consumed in another during the passage of reactants to products. If we add the equations for steps 1 through 3 together, the equation for the overall process results. A valid reaction mechanism must (CH3)3COH tert-Butyl alcohol HCl Hydrogen chloride (CH3)3CCl tert-Butyl chloride H2O Water HBr Hydrogen bromide H2O 2-Butanol Water CH3CHCH2CH3 OH 2-Bromobutane CH3CHCH2CH3 Br 4.9 Mechanism of the Reaction of Alcohols With Hydrogen Halides 139 If you have not already written out the solutions to Problems 4.9 to 4.11, you should do so now. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website