LT-GIẢI BT DẪN XUẤT HALOGEN

E1 1 HCl Chapter 9 Problems CH3COOH Cl (racemic) 4. b-Elimination: E2 (Sections 9.6, 9.7) An E2 reaction occurs in one step: simultaneous reaction with base to remove a hydrogen, formation of the alkene, and departure of the leaving group. Elimination is stereoselective, requiring an anti and coplanar arrangement of the groups being eliminated. CH3CH2O2Na1 1 CH3CH2OH 1 Cl2 Cl CH3CH2OH 5. Neighboring Group Participation (Section 9.10) Neighboring group participation is characterized by rst-order kinetics and participation of an internal nucleophile in depar- ture of the leaving group, as in hydrolysis of a sulfur or nitrogen mustard gas. The mecha- nism for their solvolysis involves two successive nucleophilic displacements. Cl N Cl 1 2 H2O HO N OH 1 2 HCl Problems Red numbers indicate applied problems. Nucleophilic Aliphatic Substitution 9.10 Draw a structural formula for the most stable carbocation with each molecular formula. (a) C4H91 (b) C3H71 (c) C5H111 (d) C3H7O1 9.11 The reaction of 1-bromopropane and sodium hydroxide in ethanol occurs by an SN2 mechanism. What happens to the rate of this reaction under the following conditions? (a) The concentration of NaOH is doubled. (b) The concentrations of both NaOH and 1-bromopropane are doubled. (c) The volume of the solution in which the reaction is carried out is doubled. 9.12 From each pair, select the stronger nucleophile. (a) H2O or OH2 (b) CH3COO2 or OH2 (c) CH3SH or CH3S2 (d) Cl2 or I2 in DMSO (e) Cl2 or I2 in methanol (f) CH3OCH3 or CH3SCH3 9.13 Draw a structural formula for the product of each SN2 reaction. Where con guration of the starting material is given, show the con guration of the product. (a) CH3CH2CH2Cl 1 CH3CH2O2Na1 ethanol (b) (CH3)3N 1 CH3I acetone (c) CH2Br 1 Na1CN2 acetone (d) (d) H3C Cl 1 CH3S2Na1 ethanol (e) CH3CH2CH2Cl 1 CH3C # C2Li1 diethyl (f) CH2Cl 1 NH3 ethanol (h) CH3CH2CH2Br 1 Na1CN2 acetone ether (g) O NH 1 CH3(CH2)6CH2Cl ethanol Unless otherwise noted all art on this page © Cengage Learning 2013 391 Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.

Chapter 9 9.14 Suppose you are told that each reaction in Problem 9.13 is a substitution reaction but Nucleophilic Substitution are not told the mechanism. Describe how you could conclude from the structure of the and b-Elimination haloalkane, the nucleophile, and the solvent that each reaction is an SN2 reaction. 9.15 Treatment of 1,3-dichloropropane with potassium cyanide results in the formation of pentanedinitrile. The rate of this reaction is about 1000 times greater in DMSO than in ethanol. Account for this difference in rate. Cl Cl 1 2 KCN NC CN 1 2 KCl 1,3-Dichloropropane Pentanedinitrile 9.16 Treatment of 1-aminoadamantane, C10H17N, with methyl 2,4-dibromobutanoate in the presence of a nonnucleophilic base, R3N, involves two successive SN2 reactions and gives compound A. Propose a structural formula for compound A. NH2 1 Br O C15H23NO2 1 2 R3NH1Br2 R3N OCH3 Br 1-Aminoadamantane Methyl A 2,4-dibromobutanoate 9.17 Select the member of each pair that shows the greater rate of SN2 reaction with KI in acetone. (a) Cl or Cl (b) Cl or Br Cl Br Br (c) or Cl (d) or 9.18 Select the member of each pair that shows the greater rate of SN2 reaction with KN3 in acetone. Br Br Br Br (a) or (b) or 9.19 What hybridization best describes the reacting carbon in the SN2 transition state? 9.20 Each carbocation is capable of rearranging to a more stable carbocation. Limiting yourself to a single 1,2-shift, suggest a structure for the rearranged carbocation. (a) (b) (c) 1 11 1 (f) (d) O 1 1 (e) 9.21 Attempts to prepare optically active iodides by nucleophilic displacement on optically active bromides using I2 normally produce racemic iodoalkanes. Why are the product iodoalkanes racemic? 9.22 Draw a structural formula for the product of each SN1 reaction. Where con guration of the starting material is given, show the con guration of the product. 392 Unless otherwise noted all art on this page © Cengage Learning 2013 Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.

(a) Cl 1 CH3CH2OH ethanol (b) 1 CH3OH Chapter 9 Cl Problems methanol S enantiomer CH3 O (c) CH3CCl 1 CH3COH acetic acid (d) Br 1 CH3OH methanol CH3 9.23 Suppose you were told that each reaction in Problem 9.22 is a substitution reaction, but you were not told the mechanism. Describe how you could conclude from the structure of the haloalkane or cycloalkene, the nucleophile, and the solvent that each reaction is an SN1 reaction. 9.24 Alkenyl halides such as vinyl bromide, CH2\"CHBr, undergo neither SN1 nor SN2 reac- tions. What factors account for this lack of reactivity? 9.25 Select the member of each pair that undergoes SN1 solvolysis in aqueous ethanol more rapidly. (a) Cl or Cl (b) Cl or Br (c) Cl or Cl (d) Cl or Cl Cl (f) Br Br (e) Cl or or 9.26 Account for the following relative rates of solvolysis under experimental conditions fa- voring SN1 reaction. O Cl Cl O Cl Relative rate of 0.2 1 109 solvolysis (SN1) 9.27 Not all tertiary haloalkanes undergo SN1 reactions readily. For example, the bicyclic com- pound shown below is very unreactive under SN1 conditions. What feature of this mol- ecule is responsible for such lack of reactivity?You will nd it helpful to examine a model of this compound. 1-Iodobicyclooctane I 9.28 Show how you might synthesize the following compounds from a haloalkane and a nucleophile. CN CN O (d) SH (a) (b) (c) O (e) (f) O (g) SH Unless otherwise noted all art on this page © Cengage Learning 2013 393 Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.

Chapter 9 9.29 3-Chloro-1-butene reacts with sodium ethoxide in ethanol to produce 3-ethoxy-1- Nucleophilic Substitution butene. The reaction is second order, rst order in 3-chloro-1-butene, and rst order in and b-Elimination sodium ethoxide. In the absence of sodium ethoxide, 3-chloro-1-butene reacts with etha- nol to produce both 3-ethoxy-1-butene and 1-ethoxy-2-butene. Explain these results. 9.30 1-Chloro-2-butene undergoes hydrolysis in warm water to give a mixture of these allylic alcohols. Propose a mechanism for their formation. OH CH3CH \" CHCH2Cl H2O CH3CH \" CHCH2OH 1 CH3CHCH \" CH2 1-Chloro-2-butene 2-Buten-1-ol 3-Buten-2-ol (racemic) 9.31 The following nucleophilic substitution occurs with rearrangement. Suggest a mecha- nism for formation of the observed product. If the starting material has the S con gura- tion, what is the con guration of the stereocenter in the product? N NaOH N OH Cl H2O 9.32 Propose a mechanism for the formation of these products in the solvolysis of this bromoalkane. Br 1 OCH2CH3 1 HBr CH3CH2OH warm 9.33 Solvolysis of the following bicyclic compound in acetic acid gives a mixture of products, two of which are shown. The leaving group is the anion of a sulfonic acid, ArSO3H. A sulfonic acid is a strong acid, and its anion, ArSO32, is a weak base and a good leaving group. Propose a mechanism for this reaction. OSO2Ar O H H OCCH3 O 1 CH3COH HH 9.34 Which compound in each set undergoes more rapid solvolysis when re uxed in ethanol? Show the major product formed from the more reactive compound. Br Br Cl or Br (a) or (b) (c) Br or Br Cl or Cl (d) 9.35 Account for the relative rates of solvolysis of these compounds in aqueous acetic acid. (CH3)3CBr Br Br Br 1 1022 1027 10212 394 Unless otherwise noted all art on this page © Cengage Learning 2013 Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.

9.36 Aacicdomshpoawrissothnaotfctohme praotuens dof(S1)N1resaocltvso1ly0s1i1stoimf tehsefabsicteyrcltihcacnomcopmoupnodusn(d1)(2a)n. dFu(2rt)hienrmacoertiec, Chapter 9 solvolysis of (1) occurs with complete retention of con guration: the nucleophile occu- Problems pies the same position on the one-carbon bridge as did the leaving 2OSO2Ar group. OSO2Ar OSO2Ar (1) (2) (a) Draw structural formulas for the products of solvolysis of each compound. (b) Account for the difference in rate of solvolysis of (1) and (2). (c) Account for complete retention of configuration in the solvolysis of (1). b-Eliminations 9.37 Draw structural formulas for the alkene(s) formed by treatment of each haloalkane or halocycloalkane with sodium ethoxide in ethanol. Assume that elimination occurs by an E2 mechanism. Br (d) (a) (b) Cl (c) Cl Cl (e) Cl (f) Br 9.38 Draw structural formulas of all chloroalkanes that undergo dehydrohalogenation when treated with KOH to give each alkene as the major product. For some parts, only one chloroalkane gives the desired alkene as the major product. For other parts, two chloroal- kanes may work. CH2 (a) (b) (c) (d) (e) 9.39 Following are diastereomers (A) and (B) of 3-bromo-3,4-dimethylhexane. On treat- ment with sodium ethoxide in ethanol, each gives 3,4-dimethyl-3-hexene as the major product. One diastereomer gives the E alkene, and the other gives the Z alkene. Which diastereomer gives which alkene? Account for the stereoselectivity of each b-elimination. H Me Me Br Me H Me Br C9C C9C Et Et Et Et (A) (B) 9.40 Treatment of the following stereoisomer of 1-bromo-1,2-diphenylpropane with sodium ethoxide in ethanol gives a single stereoisomer of 1,2-diphenylpropene. Predict whether the product has the E con guration or the Z con guration. H3C HC6H5 CH3CH2O2Na1 CH3 CH3CH2OH C6H5CH \" CC6H5 H C6H5 Br 1,2-Diphenylpropene 1-Bromo-1,2-diphenylpropane Unless otherwise noted all art on this page © Cengage Learning 2013 395 Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.

Chapter 9 9.41 Elimination of HBr from 2-bromonorbornane gives only 2-norbornene and no Nucleophilic Substitution 1-norbornene. How do you account for the regioselectivity of this dehydrohalogenation? and b-Elimination In answering this question, you will nd it helpful to look at molecular models of both 1-norbornene and 2-norbornene and analyze the strain in each. H H H H BrH HH HH 2-Norbornene H 1-Norbornene 2-Bromonorbornane 9.42 Which isomer of 1-bromo-3-isopropylcyclohexane reacts faster when re uxed with po- tassium tert-butoxide, the cis isomer or the trans isomer? Draw the structure of the ex- pected product from the faster-reacting compound. Substitution Versus Elimination 9.43 Consider the following statements in reference to SN1, SN2, E1, and E2 reactions of halo- alkanes. To which mechanism(s), if any, does each statement apply? (a) Involves a carbocation intermediate. (b) Is rst order in haloalkane and rst order in nucleophile. (c) Involves inversion of con guration at the site of substitution. (d) Involves retention of con guration at the site of substitution. (e) Substitution at a stereocenter gives predominantly a racemic product. (f) Is rst order in haloalkane and zero order in base. (g) Is rst order in haloalkane and rst order in base. (h) Is greatly accelerated in protic solvents of increasing polarity. (i) Rearrangements are common. (j) Order of reactivity of haloalkanes is 3° . 2° . 1°. (k) Order of reactivity of haloalkanes is methyl . 1° . 2° . 3°. 9.44 Arrange these haloalkanes in order of increasing ratio of E2 to SN2 products observed on reaction of each with sodium ethoxide in ethanol. (a) CH3CH2Br CH3 CH3 CH3 (b) CH3CHCH2Br (c) CH3CCH2CH3 (d) CH3CHCH2CH2Br Cl 9.45 Draw a structural formula for the major organic product of each reaction and specify the most likely mechanism by which each is formed. CH3 (a) Br 1 CH3OH methanol (b) CH3CCH2CH3 1 NaOH 80°C H2O Cl Cl O DMSO (c) + CH3CO–Na+ (R )-2-Chlorobutane (d) 1 CH3O2Na1 methanol Cl Cl (e) 1 NaI acetone Cl O R enantiomer (f) CH3CHCH2CH3 1 HCOH formic acid (g) CH3CH2O2Na1 1 CH2\" CHCH2Cl ethanol R enantiomer Unless otherwise noted all art on this page © Cengage Learning 2013 396 Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.

9.46 When cis-4-chlorocyclohexanol is treated with sodium hydroxide in ethanol, it gives Chapter 9 mainly the substitution product trans-1,4-cyclohexanediol (1). Under the same reaction Problems conditions, trans-4-chlorocyclohexanol gives 3-cyclohexenol (2) and the bicyclic ether (3). OH OH OH OH NaOH OH NaOH 1O CH3CH2OH (1) CH3CH2OH (2) (3) Cl Cl cis -4-Chloro- trans -4-Chloro- cyclohexanol cyclohexanol (a) Propose a mechanism for formation of product (1), and account for its con guration. (b) Propose a mechanism for formation of product (2). (c) Account for the fact that the bicyclic ether (3) is formed from the trans isomer but not from the cis isomer. Synthesis 9.47 Show how to convert the given starting material into the desired product. Note that some syntheses require only one step, whereas others require two or more. (a) Cl (b) Br (c) Cl OH (d) Br (e) Br Br (g) OH OH OH (f) Br Br (h) Br Br O (i) H H O 9.48 The Williamson ether synthesis involves treatment of a haloalkane with a metal alkoxide. Following are two reactions intended to give benzyl tert-butyl ether. One reaction gives the ether in good yield, and the other reaction does not. Which reaction gives the ether? What is the product of the other reaction, and how do you account for its formation? CH3 CH3 (a) CH3CO2K1 1 CH2Cl DMSO CH3COCH2 1 KCl CH3 CH3 1 KCl CH3 CH3 (b) CH2O2K1 1 CH3CCl DMSO CH3COCH2 CH3 CH3 Unless otherwise noted all art on this page © Cengage Learning 2013 397 Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.

Chapter 9 9.49 The following ethers can, in principle, be synthesized by two different combinations of Nucleophilic Substitution haloalkane or halocycloalkane and metal alkoxide. Show one combination that forms and b-Elimination ether bond (1) and another that forms ether bond (2). Which combination gives the higher yield of ether? (2) (1) (2) (1) (2) (1) CH3 CH3 O 9 CH2CH3 (b) CH39 O 9 CCH3 (c) CH2\" CHCH29 O 9 CH2CCH3 (a) CH3 CH3 9.50 Propose a mechanism for this reaction. O ClCH2CH2OH Na2CO3, H2O H2C 9 CH2 9.51 Each of these compounds can be synthesized by an SN2 reaction. Suggest a combination of haloalkane and nucleophile that will give each product. (a) CH3OCH3 (b) CH3SH (c) CH3CH2CH2PH2 (d) CH3CH2CN (e) CH3SCH2C(CH3)3 (f) (CH3)3NH1 Cl2 O N3 (h) (R)-CH3CHCH2CH2CH3 (g) C6H5COCH2C6H5 ( j) CH2\"CHCH2OCH2CH\"CH2 (i) CH2\"CHCH2OCH(CH3)2 (l) O O H (k) 1N Cl2 H Looking Ahead 9.52 OH2 is a very poor leaving group. However, many alcohols react with alkyl or aryl sulfo- nyl chlorides to give sulfonate esters. OO R 9 OH 1 R 9 S 9 Cl R3N R 9 O 9 S 9 R' 1 HCl O O (a) Explain what this change does to the leaving group ability of the substituent. (b) Suggest the product of the following reaction. O CH3CH29 O 9 S 9 C6H5 1 CH3S2Na1 DMSO O 9.53 Suggest a product of the following reaction. HI is a very strong acid. CH3CH2OCH2CH3 1 2HI R Organic Chemistry Reaction Roadmap E A 9.54 Use the roadmap you made for Problems 6.54, 7.29, and 8.28 and update it to contain C the reactions in the “Key Reactions”section as well as Table 9.1 of this chapter. Because T of their highly speci c nature, do not use reactions 3 and 5 or entry 7 of Table 9.1 on your I roadmap. O ROADMAP N 398 Unless otherwise noted all art on this page © Cengage Learning 2013 Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.

9.55 Write the products of the following sequences of reactions. Refer to your roadmap to Chapter 9 see how the combined reactions allow you to“navigate”between the different functional Problems groups. (a) 1. 1BrE2qaunivdalliegnhtt of NaOEt 1. HBr in the presence 2. An alkane (b) of peroxides and light 3. Br2 / H2O 2. NaCN An alkene 1. Br2 and light 1. 1 equivalent of NaNH2 2. KOtBu 2. Br (c) (d) 3. O(C3H3)2S 3. HHC2 l/ Lindlar's catalyst An alkane 4. An alkyne 4. 5. NaN3 Multistep Synthesis Problems Some reaction sequences are more useful than others in organic synthesis. Among the reactions you have a learned thus far, a particularly useful sequence involves the com- bination of free radical halogenation of an alkane to give a haloalkane, which is then subjected to an E2 elimination to give an alkene. The alkene is then converted to a variety of possible functional groups. Note that free radical halogenation is the only reaction you have seen that uses an alkane as a starting material. 9.56 Using your roadmap as a guide, show how to convert butane into 2-butyne. Show all reagents and all molecules synthesized along the way. ? Butane 2-Butyne 9.57 Using your roadmap as a guide, show how to convert 2-methylbutane into racemic 3-bromo-2-methyl-2-butanol. Show all reagents and all molecules synthesized along the way. Br Br ? HO HO 2-Methylbutane 3-Bromo-2-methyl-2-butanol (racemic) 9.58 Using your roadmap as a guide, show how to convert cyclohexane into hexanedial. Show all reagents and all molecules synthesized along the way. ? O Cyclohexane H H O Hexanedial 9.59. Using your roadmap as a guide, show how to convert cyclohexane into racemic 3-bromocyclohexene. Show all reagents and all molecules synthesized along the way. ? Br Br Cyclohexane 3-Bromocyclohexene (racemic) Unless otherwise noted all art on this page © Cengage Learning 2013 399 Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.

Chapter 9 9.60 Another important pattern in organic synthesis is the construction of C!C bonds. Using Nucleophilic Substitution your roadmap as a guide, show how to convert propane into hex-1-en-4-yne. You must and b-Elimination use propane as the source of all of the carbon atoms in the hex-1-en-4-yne product. Show all reagents needed and all molecules synthesized along the way. ? Propane Hex-1-en-4-yne 9.61 Using your roadmap as a guide, show how to convert propane into butyronitrile. You must use propane and sodium cyanide as the source of all of the carbon atoms in the butyronitrile product. Show all reagents and all molecules synthesized along the way. NaCN ? Sodium cyanide Propane Butyronitrile N Reactions in Context 9.62 Fluticasone is a glucocorticoid drug that has been used to treat asthma. In the synthesis of uticasone, the following transformation is used that involves a limiting amount of sodium iodide. Analyze the structure using the chemistry you learned in this chapter and draw the product of the reaction. Cl S O O HO CH3 O CH3 H CH3 FH NaI acetone O F 9.63 The following reaction sequence was used in the synthesis of several derivatives of pros- taglandin C2. Analyze the structure using the chemistry you learned in this chapter and draw the structures of the synthetic intermediates A and B. OO 1. NaNH2, THF(solvent) A NaCN B (racemic) 2. Br Cl DMSO (racemic) (racemic) 9.64 The following reaction was used in the synthesis of various prostaglandin derivatives. Analyze the structure using the chemistry you learned in this chapter and draw the prod- uct of the reaction. Br OH H O O excess tBuOK t BuOH 400 HO OH Unless otherwise noted all art on this page © Cengage Learning 2013 Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.