1559T_ch06_099-11210/22/0520:19Page99 ⊕ EQA 6 Properties and Reactions of Haloalkanes: Bimolecular Nucleophilic Substitution erties lent bon pres nted in They are the ha es.containing a polarized carbon( chemistry of functional groups,this chapter should be examined particularly closely. ail here are fully applicable later on.even though later presentations may not be as compre ebe ohelp eplain the chavor ofhaloakanes.Comprchending this matcr sense is in the long run more usetul than remembering every last deta Outline of the Chapter 6-1 Physical Properties of Haloalkanes 6-2 Nucleophilic Substitution The nature of this functional group,and an introduction to its most characteristic reaction 6-3 Reaction Mechanisms Describing how reactions occur.A very important section. important section. apters 4 6-7 The Leaving Group 6-8 The Nucleophile 6-9 The Structure of the Substrate The roles of the major variables on the favorability of the single reaction type under discussion. 99
6 Properties and Reactions of Haloalkanes: Bimolecular Nucleophilic Substitution Referring to Chapter 1, recall that polarized covalent bonds are at the heart of most of organic reaction chemistry. Here, for the first time, the properties and chemical behavior of molecules containing a polarized covalent bond are presented in full detail. They are the haloalkanes, containing a polarized carbon()– halogen() bond. Because the reactions here serve as models for many subsequent presentations of the chemistry of organic functional groups, this chapter should be examined particularly closely. Many concepts discussed in detail here are fully applicable later on, even though later presentations may not be as comprehensive. With this and the next chapter we really start covering typical organic chemistry. Now you get your first opportunity to see the “big picture” with respect to one portion of this subject. In addition, much of what you’ve seen up to now will be used to help explain the behavior of haloalkanes. Comprehending this material in a general overall sense is in the long run more useful than remembering every last detail. Outline of the Chapter 6-1 Physical Properties of Haloalkanes 6-2 Nucleophilic Substitution The nature of this functional group, and an introduction to its most characteristic reaction. 6-3 Reaction Mechanisms Describing how reactions occur. A very important section. 6-4 Mechanism of Nucleophilic Substitution: Kinetics The first section in the text to cover in detail the mechanism of a specific polar reaction. Also a very important section. 6-5 Stereochemistry Tying together this reaction with material in Chapter 5. 6-6 Consequences of Inversion in SN2 Reactions Further implications of material in Chapters 4 and 5. 6-7 The Leaving Group 6-8 The Nucleophile 6-9 The Structure of the Substrate The roles of the major variables on the favorability of the single reaction type under discussion. 99 1559T_ch06_099-112 10/22/05 20:19 Page 99
15597.ch06_099-11210/22/0520:19Page100 EQA 100 chapter 6 PROPERTES AND REACTIONS OF HALOALKANES:BIMOLECULAR NUCLEOPHILIC SUBSTTTUTON Keys to the Chapter ng the appre 6-2.Nucleophilic Substitution At this stage we begin a detailed discussion of our first major class of polar reactions.Note the following features csubstitutions have a similar general appearance,with a similar cast of characters.so to Nucleophile Substrate Whenever a new reaction class is p esented.analyze the various examples p sented from the point of view of the common roles played by the chemical species involved.You should do this now for all the in the ta in this stan strate ybecomesaond to (positiely polanzed)caon Electron-richom Electrophilic atom each other.Do this now for the examples in the reaction table in the text section. on class and understand in a fundamental way s organic chemistr y by understandin instead of by memorizing. 6-3.Reactio Mecha
100 • Chapter 6 PROPERTIES AND REACTIONS OF HALOALKANES: BIMOLECULAR NUCLEOPHILIC SUBSTITUTION Keys to the Chapter 6-1. Physical Properties The carbon–halogen bond is the focal point of this chapter. Its polarization is the major feature governing the physical and chemical behavior of these molecules. Differences among the four halogens will affect the degree to which a haloalkane exhibits any given physical or chemical characteristic. This section reveals many qualitative similarities among the haloalkanes. Understand these first; you will then be in a better position to appreciate the differences that are presented later. 6-2. Nucleophilic Substitution At this stage we begin a detailed discussion of our first major class of polar reactions. Note the following features: 1. All nucleophilic substitutions have a similar general appearance, with a similar cast of characters, so to speak. Using the first example in the text table, we have HO CH3Cl 88n CH3OH Cl Nucleophile Substrate Product Leaving group Whenever a new reaction class is presented, analyze the various examples presented from the point of view of the common roles played by the chemical species involved. You should do this now for all the examples in the table in this text section. That is, in each case identify the nucleophile, substrate, product, and leaving group. Start getting used to the variety of species that belong to each category. 2. All nucleophilic substitutions are electrostatically sensible. In every case an electron-rich atom in the nucleophile ultimately becomes attached via a new bond to an electrophilic (positively polarized) carbon atom in the substrate. Opposite charges attract! Again, whenever a new reaction class is presented, analyze the examples given on the basis of electrostatics. Focus on the logical consequences of oppositely charged or polarized atoms attracting each other. Do this now for the examples in the reaction table in the text section. When you analyze the components involved in a new reaction class and understand in a fundamental way why the reaction is reasonable, you have taken the first step toward learning organic chemistry by understanding instead of by memorizing. 6-3. Reaction Mechanisms The mechanism of a reaction describes in detail when and how bonding changes occur. One useful feature of such information is its predictive value: Mechanistic understanding can tell us whether an unknown new example of a reaction is likely to work or not. This knowledge is important in synthesis: the preparation of new molecules from old ones for, for example, medicinal purposes or theoretical study. 6-4, 6-5, and 6-6. Mechanism of Nucleophilic Substitution Section 6-4 describes one of the more common methods of deriving mechanistic information: kinetic experiments. Section 6-5 describes another common method: experiments involving the observation of stereochemO Cl H H H H C Cl HO CH3 Electron-rich atom Electrophilic atom New bond 1559T_ch06_099-112 10/22/05 20:19 Page 100
1559T_ch06_099-11210/22/0520:19Pa9e101 ⊕ EQA Keys to the Chopler·101 twenticth century.The key features,second-order kinetics and inversion of configuration at the substrate ns in hapter.Then the a to be made apter explore the most important of these.It should be pointed out that many of the observ tions s were predic ahead of time on the of the logica 2 mech a reaction of molecules you may never have seen before on the basis of your knowledge of reaction mech- anis of shor indicated by arrows that represent the movement of pairs of electrons.For the 2 mechanism.a one-step process,we have: H:+aH,一H0-CH+a on.bond nism arrows depict the movement of pairs of electrons.not the m rement of atoms.This is a logical result of the fact that chemical reactions are due to changes in bonds,and bonds are made out of electrons.Practice action of an acid and a base,is shown below 0:+ia6一o-HH,o+a 6-7,6-8,and 6-9.The SN2 Reaction in Depth These sections explore the effects of changing three variables on the S2 reaction rate:leaving group.uce ophile,and substrate structure.A a knowledge of the fect of the variable on the rate of reaction is considered.This should tell you that the point of cach discus sion will be:Hov does changing this variable affect the activation energy- the energy of the transition state may not say It in s ny words every t .the out th nat's what w eration of Be e the. to leave”i inggroup.Stable leaving groupsare therefore better (interpret:faste)leaving groups.The parallel betwe pter is the easies oups are strone they are the co aving groups out of bad ones.Notice how such fundamental concepts as acid/base strength can play pivotal roles in organic chemistry
Keys to the Chapter • 101 ical changes. By combining information from these and other types of experiments, the mechanistic picture of the bimolecular nucleophilic displacement, or SN2 reaction, was developed over the first 30-odd years of the twentieth century. The key features, second-order kinetics and inversion of configuration at the substrate carbon, are common to all the reactions in this chapter. The mechanism allows predictions to be made concerning the effects of changing any of a number of variables in the SN2 reaction. The last four sections of the chapter explore the most important of these. It should be pointed out that many of the observations described in these sections were predicted ahead of time on the basis of the logical implications of the SN2 mechanism. Part of your job as a student in organic chemistry will be to develop the ability to predict the result of a reaction of molecules you may never have seen before on the basis of your knowledge of reaction mechanisms associated with the functional groups the molecules contain. One final comment on mechanisms in general: There exists a common sort of shorthand way of writing organic reaction mechanisms. First, each step is written separately. Second, bonding changes in each step are indicated by arrows that represent the movement of pairs of electrons. For the SN2 mechanism, a one-step process, we have: The two arrows show (1) movement of a pair of electrons from oxygen to carbon to form the new C— O bond and (2) movement of a pair of electrons from the C—Cl bond to chlorine to form the chloride ion. Mechanism arrows depict the movement of pairs of electrons, not the movement of atoms. This is a logical result of the fact that chemical reactions are due to changes in bonds, and bonds are made out of electrons. Practice using “electron pushing” in mechanisms as frequently as you can so that you can get used to the technique. Note that proper use of electron-pair arrows automatically results in the correct Lewis structures for the products of a reaction, including charges, if any. An example of its application to an even simpler reaction, the reaction of an acid and a base, is shown below. 6-7, 6-8, and 6-9. The SN2 Reaction in Depth These sections explore the effects of changing three variables on the SN2 reaction rate: leaving group, nucleophile, and substrate structure. All the material in these sections derives logically from a knowledge of the mechanism and an awareness of the role each of the three variables can play. In each of these sections the effect of the variable on the rate of reaction is considered. This should tell you that the point of each discussion will be: How does changing this variable affect the activation energy—the energy of the transition state relative to that of the starting materials? We may not say it in so many words every time, but that’s what we mean. Even if the discussion is totally qualitative, and no actual rate data are given, the focus of such a discussion will still be the effect of the variable in question on relative transition state energy. Consideration of the leaving group is fairly simple. Because the leaving group is “beginning to leave” in the SN2 transition state, the energy of the transition state will reflect to some extent the stability of the leaving group. Stable leaving groups are therefore better (interpret: “faster”) leaving groups. The parallel between leaving-group ability and nonbasic character drawn in the chapter is the easiest one to work with and is fairly reliable. “Good” leaving groups are usually the conjugate bases of strong acids (Table 6-4). “Bad” leaving groups are strong bases, i.e., they are the conjugate bases of weak acids. Later you will learn how to manufacture good leaving groups out of bad ones. Notice how such fundamental concepts as acid/base strength can play pivotal roles in organic chemistry. Cl HO H Cl HO H (H2O) Cl HO CH3 Cl HO CH3 1559T_ch06_099-112 10/22/05 20:19 Page 101
1559T_ch06_099-11210/22/0520:19Pa9e103 ⊕ EQA Solutions to Problems.103 30.Stereocentersare marked with an asterisk and numbers of stereoisomers are given in parentheses BrCH2CH2CH2CH2CH CH.CHBrCH2CH2CH CH,CH,CHBrCH,CH Bromopentane (2 ethylbutane CH CH;CH2CHCH2Br BrCH.CCHs 1-Bromo-2-methylbutane(2) H-rmod thylpropan 31.See 29 and 30. Reaction Nucleophile Substrate Leaving group 1. HO:- CH.CI 2. CHO- 西 CH.CHBICH.CH, Br- :NC (CH)CHCHI CH,S: C 、 H CH,CHI :B(CHs) CH,Br Br- (b)The N may act as a nucleophilic atom in cyanide (CN-).The reaction would then proceed as follows cH,c,9+=c:一r+ CHs H ,CcH,-是c:一H,CcH,-=c
Solutions to Problems • 103 30. Stereocenters are marked with an asterisk and numbers of stereoisomers are given in parentheses. 31. See 29 and 30. 32. In the answers below, the nucleophilic atom in the nucleophile and the electrophilic atom in the substrate are both underlined. Reaction Nucleophile Substrate Leaving group 1. CH3Cl Cl 2. CH3CH2I I 3. CH3CHBrCH2CH3 Br 4. (CH3)2CHCH2I I 5. Br 6. CH3CH2I I 7. CH3Br Br 33. (a) in reaction 4. (b) The N may act as a nucleophilic atom in cyanide (CN). The reaction would then proceed as follows: CH3CCH2 N C H I I CH3 CH3CCH2 N C H CH3 CH3CCH2 H CH3 An organic “isonitrile” N C N C N C P(CH3)3 NH3 CHBr CH3S N C I CH3O HO BrCH2CH2CH2CH2CH3 1-Bromopentane CH2CHBrCH2CH2CH3 2-Bromopentane (2) CH3CH2CHBrCH2CH3 3-Bromopentane * BrCH2CH2CHCH3 1-Bromo-3-methylbutane * CH3 CH3CHBrCHCH3 2-Bromo-3-methylbutane (2) CH3 CH3CH2CBrCH3 2-Bromo-2-methylbutane CH3 * CH3CH2CHCH2Br 1-Bromo-2-methylbutane (2) CH3 BrCH2CCH3 1-Bromo-2,2-dimethylpropane CH3 CH3 1559T_ch06_099-112 10/22/05 20:19 Page 103
15597.ah06_099-11210/24/0504:49 M Page104 EQA 104 chapter 6 PROPERTES AND REACTIONS OF HALOALKANES:BIMOLECULAR NUCLEOPHILIC SUBSTTTUTON 34.Answers are presented in the same manner as for Problem 32.Arrows mark electrophilic atoms. Reaction Nucleophile Substrate Leaving group Product NH: [入B sH 0 (c) 入1 (d) H CI H (e) 35.Bimolecular displacement is first order in each component. (a)Rate=A[CH CllKSCN]:2 x 10-8 mol L-'s-1 k(0.1 MX(0.1 M).so k=2x 10-L mol-'s-1. (b)The three rates are (i)4 (ii)1.20:and (ii)3.2x10-7 mol L-'s-.respectively. 36.(a)CH;CH-CHaI (b)(CHa)CHCH2CN (c)CH;OCH(CH3)2 (f)(CHa)2CHN(CHa)3*-OSO2CHs 37.(a)Starting material is R. H CH3 Product is S. CH-CH3 (b)Starting material is(,35)-2-bromo-3-chlorobutane. H (e)Starting material is(15.3R)-3-chlorocyclohexanol (the position of the OH group is understood to be C1)
34. Answers are presented in the same manner as for Problem 32. Arrows mark electrophilic atoms. Reaction Nucleophile Substrate Leaving group Product (a) NH2 CH3I I CH3NH2 (b) HS Br (c) I CF3SO3 (d) N3 Cl (e) CH3Cl Cl (f) SeCN I 35. Bimolecular displacement is first order in each component. (a) Rate k[CH3Cl][KSCN]: 2 108 mol L1 s 1 k(0.1 M)(0.1 M), so k 2 106 L mol1 s 1 . (b) The three rates are (i) 4 108 ; (ii) 1.2 107 ; and (iii) 3.2 107 mol L1 s 1 , respectively. 36. (a) CH3CH2CH2I (b) (CH3)2CHCH2CN (c) CH3OCH(CH3)2 (d) CH3CH2SCH2CH3 (e) (f ) (CH3)2CHN(CH3)3 OSO2CH3 37. (a) Starting material is R. (b) Starting material is (2S,3S)-2-bromo-3-chlorobutane. (c) Starting material is (1S,3R)-3-chlorocyclohexanol (the position of the OH group is understood to be C1). CH3 CH3 Product is (2R,3R)-2,3-diiodobutane. H I I H CH3 Product is S. CH2CH3 Br H CH2Se(CH2CH3)2 Cl SeCN I H3C CH3 N CH3 N H Cl N3 H I S O O O CF3 Br SH 104 • Chapter 6 PROPERTIES AND REACTIONS OF HALOALKANES: BIMOLECULAR NUCLEOPHILIC SUBSTITUTION 1559T_ch06_099-112 10/24/05 04:49 PM Page 104