chapter 8 NUCLEOPHILIC SUBSTITUTION SOLUTIONS TO TEXT PROBLEMS 8.1 Identify the nucleophilic anion in each reactant. The nucleophilic anion replaces bromine as a sub- (b) Potassium ethoxide serves as a source of the nucleophilic anion CH CH,O CH, CH,O: CH Bra CH3CH2OCH3 Br: Ethoxide ion Methyl bromide Ethyl methyl ether Bromide ion B3 Br: Br Benzoate ion Methyl bromide Methyl benzoate (d) Lithium azide is a source of the azide ion. It reacts with methyl bromide to give methyl azide NN=N:+ CH B1 CHNE N=N:+1 Azide ior Methyl azide Bromide ion (nucleophile) (e) The nucleophilic anion in KCN is cyanide(CEN: ) The carbon atom is negatively charged and is normally the site of nucleophilic reactivity Cyanide Methyl bromide Methyl cyanide romine ion 184 Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
CHAPTER 8 NUCLEOPHILIC SUBSTITUTION SOLUTIONS TO TEXT PROBLEMS 8.1 Identify the nucleophilic anion in each reactant. The nucleophilic anion replaces bromine as a substituent on carbon. (b) Potassium ethoxide serves as a source of the nucleophilic anion CH3CH2O. (c) (d) Lithium azide is a source of the azide ion. It reacts with methyl bromide to give methyl azide. (e) The nucleophilic anion in KCN is cyanide ( ). The carbon atom is negatively charged and is normally the site of nucleophilic reactivity. CH3Br CH3C N Br Methyl cyanide Bromide ion (product) Methyl bromide N C Cyanide ion (nucleophile) C N N N N N N CH3Br CH3N Br Methyl azide Bromide ion (product) Methyl bromide Azide ion (nucleophile) N N N CH3Br Br Benzoate ion Methyl bromide Methyl benzoate Bromide ion C O O C OCH3 O CH3CH2O CH3Br CH3CH2OCH3 Br Ethyl methyl ether Bromide ion (product) Ethoxide ion Methyl bromide (nucleophile) 184 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
NUCLEOPHILIC SUBSTITUTION 185 (f) The anion in sodium hydrogen sulfide(NasH)is : SH CH3SH Br Hydrogen Methyl bro Methanethiol Bromide ion (g) Sodium iodide is a source of the nucleophilic anion iodide ion, I The reaction of sodium iodide with alkyl bromides is usually carried out in acetone to precipitate the sodium bromide Br: lodide ion Methyl bromide Methyl iodide Bromide ion 8.2 Write out the structure of the starting material. Notice that it contains a primary bromide and a pri mary chloride. Bromide is a better leaving group than chloride and is the one that is displaced faster by the nucleophilic cyanide ion. CICH..Br NaCN ethanokwater CICHCH2CHC≡N 1-Bromo-3-chloropropane 8.3 No, the two-step sequence is not consistent with the observed behavior for the hydrolysis of methyl bromide. The rate-determining step in the two-step sequence shown is the first step, ionization of methyl bromide to give methyl cation CH Br CH,+ Br 2. CH2 HO In such a sequence the nucleophile would not participate in the reaction until after the rate- determining step is past, and the reaction rate would depend only on the concentration of methyl bromide and be independent of the concentration of hydroxide ion. The predicted kinetic behavior is first order. Second order kinetic behavior is actually observed for methyl bromide hydrolysis, so the proposed mechanism cannot be correct. 8.4 Inversion of configuration occurs at the stereogenic center. When shown in a Fischer projection, his corresponds to replacing the leaving group on the one side by the nucleophile on the opposite NaOH HO-+H CH(CH2)4CH3 CH2(CH2)4CH3 (S-(+)-2-Bromooctan (R)(-)-2-Octanol 8.5 The example given in the text illustrates inversion of configuration in the S2 hydrolysis of (S)-(+)-2-bromooctane, which yields(R)-(-)-2-octanol. The hydrolysis of(R)-(-)-2-bromooctane exactly mirrors that of its enantiomer and yields(S)-(+)-2-octanol ants must yield optically inactive products 8.6 Sodium iodide in acetone is a reagent that converts alkyl chlorides and bromides into alkyl io- dides by an Sn2 mechanism. Pick the alkyl halide in each pair that is more reactive toward Sn2 Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
( f ) The anion in sodium hydrogen sulfide (NaSH) is . (g) Sodium iodide is a source of the nucleophilic anion iodide ion, . The reaction of sodium iodide with alkyl bromides is usually carried out in acetone to precipitate the sodium bromide formed. 8.2 Write out the structure of the starting material. Notice that it contains a primary bromide and a primary chloride. Bromide is a better leaving group than chloride and is the one that is displaced faster by the nucleophilic cyanide ion. 8.3 No, the two-step sequence is not consistent with the observed behavior for the hydrolysis of methyl bromide. The rate-determining step in the two-step sequence shown is the first step, ionization of methyl bromide to give methyl cation. 1. 2. In such a sequence the nucleophile would not participate in the reaction until after the ratedetermining step is past, and the reaction rate would depend only on the concentration of methyl bromide and be independent of the concentration of hydroxide ion. Rate k[CH3Br] The predicted kinetic behavior is first order. Second order kinetic behavior is actually observed for methyl bromide hydrolysis, so the proposed mechanism cannot be correct. 8.4 Inversion of configuration occurs at the stereogenic center. When shown in a Fischer projection, this corresponds to replacing the leaving group on the one side by the nucleophile on the opposite side. 8.5 The example given in the text illustrates inversion of configuration in the SN2 hydrolysis of (S)-()-2-bromooctane, which yields (R)-()-2-octanol. The hydrolysis of (R)-()-2-bromooctane exactly mirrors that of its enantiomer and yields (S)-()-2-octanol. Hydrolysis of racemic 2-bromooctane gives racemic 2-octanol. Remember, optically inactive reactants must yield optically inactive products. 8.6 Sodium iodide in acetone is a reagent that converts alkyl chlorides and bromides into alkyl iodides by an SN2 mechanism. Pick the alkyl halide in each pair that is more reactive toward SN2 displacement. NaOH SN2 CH3 CH2(CH2)4CH3 H Br CH3 CH2(CH2)4CH3 HO H (S)-()-2-Bromooctane (R)-()-2-Octanol CH3 HO CH3OH fast CH3Br CH3 Br slow ClCH2CH2CH2Br 1-Bromo-3-chloropropane 4-Chlorobutanenitrite NaCN ethanol–water ClCH2CH2CH2C N CH3Br Br CH3 Iodide ion Methyl bromide Methyl iodide Bromide ion I I acetone I HS CH3Br CH3SH Br Hydrogen Methyl bromide Methanethiol Bromide ion sulfide ion SH NUCLEOPHILIC SUBSTITUTION 185 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
186 NUCLEOPHILIC SUBSTITUTION (b) The less crowded alkyl halide reacts faster in an SN2 reaction. 1-Bromopentane is a primary alkyl halide and so is more reactive than 3-bromopentane, which is secondary BrCH,CH,CH,CH,CH CH, CH, CHCH, CH 1-Bromopentane 3-Bromopentane more reactive in SN2)(secondary; less reactive in SN2) (c) Both halides are secondary, but fluoride is a poor leaving group in nucleophilic substitution reactions. Alkyl chlorides are more reactive than alkyl fluorides CHa CHCH, CH, CH, CH3 CHCH,CH, CH3 2-Chloropentane 2-Fluoropentane ( more reactive) (less reactive) (d) A secondary alkyl bromide reacts faster under Sn2 conditions than a tertiary one CH, CHCH, CH,CHCH; CH,, CH,, CH3 2-Bromo-5-methy lhexane 2-Bromo-2-methylhexan (secondary; more reactive in Sn2) (tertiary; less reactive in SN2) (e) The number of carbons does not matter as much as the degree of substitution at the reaction site. The primary alkyl bromide is more reactive than the secondar BrCH,(CH,)CH CH CHCH 1-Bromodecane rimary:more reactive in Sx2) (secondary; less reactive in SN2) 8.7 Nitrite ion has two potentially nucleophilic sites, oxygen and nitroger 2: R+: Nitrite ion Alkyl iodide Iodide ion N-R 88 Nitrite io Alkyl iodide Nitroalkane lodide ion Thus, an alkyl iodide can yield either an alkyl nitrite or a nitroalkane depending on whether the oxy gen or the nitrogen of nitrite ion attacks carbon. Both do, and the product from 2-iodooctane is a mixture of CH,CH(CH2)5CH3 and CH,CH(CH,)5CH3 Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
186 NUCLEOPHILIC SUBSTITUTION (b) The less crowded alkyl halide reacts faster in an SN2 reaction. 1-Bromopentane is a primary alkyl halide and so is more reactive than 3-bromopentane, which is secondary. (c) Both halides are secondary, but fluoride is a poor leaving group in nucleophilic substitution reactions. Alkyl chlorides are more reactive than alkyl fluorides. (d) A secondary alkyl bromide reacts faster under SN2 conditions than a tertiary one. (e) The number of carbons does not matter as much as the degree of substitution at the reaction site. The primary alkyl bromide is more reactive than the secondary. 8.7 Nitrite ion has two potentially nucleophilic sites, oxygen and nitrogen. Thus, an alkyl iodide can yield either an alkyl nitrite or a nitroalkane depending on whether the oxygen or the nitrogen of nitrite ion attacks carbon. Both do, and the product from 2-iodooctane is a mixture of CH3CH(CH2)5CH3 CH3CH(CH2)5CH3 ONO NO2 and N R N R Nitrite ion Alkyl iodide Nitroalkane Iodide ion I I O O O O ON R O I ON R O Nitrite ion Alkyl iodide Alkyl nitrite Iodide ion I BrCH2(CH2)8CH3 CH3CHCH3 Br 2-Bromopropane (secondary; less reactive in SN2) 1-Bromodecane (primary; more reactive in SN2) CH3CHCH2CH2CHCH3 Br CH3 CH3CCH2CH2CH2CH3 Br CH3 2-Bromo-2-methylhexane (tertiary; less reactive in SN2) 2-Bromo-5-methylhexane (secondary; more reactive in SN2) CH3CHCH2CH2CH3 F 2-Fluoropentane (less reactive) CH3CHCH2CH2CH3 Cl 2-Chloropentane (more reactive) BrCH2CH2CH2CH2CH3 CH3CH2CHCH2CH3 Br 3-Bromopentane (secondary; less reactive in SN2) 1-Bromopentane (primary; more reactive in SN2) Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
NUCLEOPHILIC SUBSTITUTION 187 8.8 Solvolysis of alkyl halides in alcohols yields ethers as the products of reaction (CH3)CBr CH,OH -(CH3)3COCH3 HBr Methanol tert-Butyl methy Hydrogen he reaction proceeds by an Snl mechanism. (CH3) C-Br (CH3)3 Br tert-Butyl tert-Butyl Bromide bromid CH CH3 (CH3)2 tert-Butyl Methanol tert-Butyloxonium (CH3)2C-O3 Br: -(CH3)3C-OCH3 H-Br terT-Butyloxonium BromI Hydrogen methyl 8.9 The reactivity of an alkyl halide in an SNl reaction is dictated by the ease with which it ionizes form a carbocation. Tertiary alkyl halides are the most reactive, methyl halides the least reactive (b) Cyclopentyl iodide ionizes to form a secondary carbocation, and the carbocation from 1-methylcyclopentyl iodide is tertiary. The tertiary halide is more reactive (tertiary: more reactive in SI)(secondary; less reactive in SNI) (c) Cyclopentyl bromide ionizes to a secondary carbocation. l-Bromo-2, 2-dimethyl-propane is a primary alkyl halide and is therefore less reactive. ( CH3)3CCH,Br Cyclopentyl bromide I-Bromo-2, 2-dimethylpropane (secondary; more reactive in SNI)(primary: less reactive in SNl) (d) lodide is a better leaving group than chloride in both SNI and Sn2 reactions (CH3)3CI (CH3)CCI m tert-Butyl chloride (less reactive) Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
8.8 Solvolysis of alkyl halides in alcohols yields ethers as the products of reaction. The reaction proceeds by an SN1 mechanism. 8.9 The reactivity of an alkyl halide in an SN1 reaction is dictated by the ease with which it ionizes to form a carbocation. Tertiary alkyl halides are the most reactive, methyl halides the least reactive. (b) Cyclopentyl iodide ionizes to form a secondary carbocation, and the carbocation from 1-methylcyclopentyl iodide is tertiary. The tertiary halide is more reactive. (c) Cyclopentyl bromide ionizes to a secondary carbocation. 1-Bromo-2,2-dimethyl-propane is a primary alkyl halide and is therefore less reactive. (d) Iodide is a better leaving group than chloride in both SN1 and SN2 reactions. (CH3)3CI (CH3)3CCl tert-Butyl chloride (less reactive) tert-Butyl iodide (more reactive) H Br Cyclopentyl bromide (secondary; more reactive in SN1) 1-Bromo-2,2-dimethylpropane (primary; less reactive in SN1) (CH3)3CCH2Br H I 3C 1-Methylcyclopentyl iodide (tertiary; more reactive in SN1) H I Cyclopentyl iodide (secondary; less reactive in SN1) tert-Butyloxonium ion (CH3)3C O H CH3 tert-Butyl methyl ether (CH3)3C OCH3 Bromide ion Br Hydrogen bromide H Br tert-Butyloxonium ion tert-Butyl cation Methanol fast (CH3)3C O (CH3)3C O CH3 H CH3 H (CH3)3C Br Bromide ion tert-Butyl bromide tert-Butyl cation (CH3)3C Br slow (CH3)3CBr (CH CH3OH HBr 3)3COCH3 Hydrogen bromide tert-Butyl methyl ether tert-Butyl Methanol bromide NUCLEOPHILIC SUBSTITUTION 187 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
188 NUCLEOPHILIC SUBSTITUTION 8.10 The alkyl halide is tertiary and so undergoes hydrolysis by an SxI mechanism. The carbocation car be captured by water at either face. A mixture of the axial and the equatorial alcohols is formed is-1, 4-Dimethylcyclohexyl bromide H, C trans-1, 4-Dimethylcyclohexanol Carbocation intermediate cis-1, 4-Dimethylcyclohexanol The same two substitution products are formed from trans-1, 4-dimethylcyclohexyl bromide be- cause it undergoes hydrolysis via the same carbocation intermediate 8.11 Write chemical equations illustrating each rearrangement process Hydride shift: H,C-C--CCH H C-C- Tertiary carbocation Methyl shift: H3CCC--CH3 H CH. CH Secondary carbocation Rearrangement by a hydride shift is observed because it converts a secondary carbocation to a more stable tertiary one. A methyl shift gives a secondary carbocation--in this case the same carbocation as the one that existed prior to rearrangement 8.12(b) Ethyl bromide is a primary alkyl halide and reacts with the potassium salt of cyclohexanol by substitution CH CHBr OCH,CH3 Ethyl bromide Potassium Cyclohexyl ethyl ether (c) No strong base is present in this reaction; the nucleophile is methanol itself, not methoxide. It reacts with sec-butyl bromide by substitution, not elimination CH_CHCH,CH3 CH,OH CH CHCH, CH3 OCH sec-Butyl bromide sec-Butyl methyl ether Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
8.10 The alkyl halide is tertiary and so undergoes hydrolysis by an SN1 mechanism. The carbocation can be captured by water at either face. A mixture of the axial and the equatorial alcohols is formed. The same two substitution products are formed from trans-1,4-dimethylcyclohexyl bromide because it undergoes hydrolysis via the same carbocation intermediate. 8.11 Write chemical equations illustrating each rearrangement process. Hydride shift: Methyl shift: Rearrangement by a hydride shift is observed because it converts a secondary carbocation to a more stable tertiary one. A methyl shift gives a secondary carbocation—in this case the same carbocation as the one that existed prior to rearrangement. 8.12 (b) Ethyl bromide is a primary alkyl halide and reacts with the potassium salt of cyclohexanol by substitution. (c) No strong base is present in this reaction; the nucleophile is methanol itself, not methoxide. It reacts with sec-butyl bromide by substitution, not elimination. CH3OH sec-Butyl bromide CH3CHCH2CH3 Br CH3CHCH2CH3 OCH3 sec-Butyl methyl ether OK Potassium cyclohexanolate OCH2CH3 Cyclohexyl ethyl ether CH3CH2Br Ethyl bromide Secondary carbocation C C H H CH3 H3C CH3 C C H CH3 H3C H CH3 Tertiary carbocation C CCH3 H CH3 H H3C C C H H H3C CH3 CH3 cis-1,4-Dimethylcyclohexyl bromide CH3 Br H3C trans-1,4-Dimethylcyclohexanol OH CH3 H3C cis-1,4-Dimethylcyclohexanol CH3 OH H3C Carbocation intermediate CH3 H3C H2O H2O 188 NUCLEOPHILIC SUBSTITUTION Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website