1 Substituição Nucleofílica 1. Identifique qual dos compostos em cada par de haloalcanos abaixo reage mais rapidamente em uma reação SN2. Explique sua resposta. (a) Cl Cl (b) Br Br (c) Cl Cl (d) Br 7.39 In Chapter 10, we will see that an acetylide ion (formed by treat 2. Identifique o núcleofilo mais forte. (a) NaSH vs. H2S (b) NaOH vs. H2O (c) MeO – /MeOH vs. MeO – /DMSO 3. Coloque os compostos abaixo em ordem crescente de reatividade frente a azida de sódio. Explique a sua escala. Br Me Br Br O Br Br 4. Qual dos compostos em cada par reage mais rapidamente em uma reação do tipo SN1. Explique a sua resposta. (a) Cl Cl (b) Br Br (c) Cl Cl (d) Cl OTs 5. Considere a seguinte reação: Br CN NaBr NaCN DMSO + a) Como a velocidade da reação será afetada se a concentraçãoo de haloalcano for duplicada? b) Como a velocidade da reação será afetada se a concentraçãoo de NaCN for duplicada? 6. Considere a seguinte reação: H 2 O HBr OH Br + a) Como a velocidade da reação será afetada se a concentração de álcool for duplicada? b) Como a velocidade da reação será afetada se a concentração de HBr for duplicada? 7. Classifique cada um dos seguintes solventes como prótico ou aprótico. a) DMF b) Etanol c) DMSO d) Água e) Amônia 8. Quando o álcool oticamente ativo abaixo é tratado com HBr, uma mistura racêmica de brometos de alquila é obtida: HBr H 2 O OH Br Racemic mixture + Escreva o mecanismo da reação e explique o resultado estereoquímico. 9. Proponha um mecanismo para as seguintes transformações: (a) OH H 2 O HCl Cl + (b) NaBr Br O O ONa O + 10. A reação abaixo é muito lenta: Br OH HBr H 2 O + a) Identifique o mecanismo. b) Explique porque esta reação é lenta. c) Quando hidróxido é usado no lugar de água a reação é muito rápida. Escreva o mecanismo desta reação e explique esse resultado.
Transcript
1
Substituição Nucleofílica
1. Identifique qual dos compostos em cada par de
haloalcanos abaixo reage mais rapidamente em uma
reação SN2. Explique sua resposta. choice in each case.
(a)
Cl
Cl (b) Br Br
(c)
Cl Cl
(d) Br
7.39 In Chapter 10, we will see that an acetylide ion (formed by treat-
2. Identifique o núcleofilo mais forte.
(a) NaSH vs. H2S
(b) NaOH vs. H2O
(c) MeO–/MeOH vs. MeO–/DMSO
3. Coloque os compostos abaixo em ordem crescente
de reatividade frente a azida de sódio. Explique a sua
escala.
138 Solutions Manual to accompany Organic Chemistry
OH
ArS
OH
O O
OH2 HO O
SN1
PROB LEM 2 Arrange the following in order of reactivity towards the nucleophile sodium azide. Give a brief comment for each compound to explain what factor influences its place in the reactivity scale.
Br Me Br Br
O
Br
Br
Purpose of the problem
Revision of the factors affecting reactivity in a series of SN2-reactive molecules.
Suggested solution
None of these compounds has structural features necessary to promote SN1 (not even the third: notice that the bromine is attached to a primary carbon, even though there is a tert-butyl group in the molecule), so we need to think about SN2 reactivity only. In general, steric hindrance slows down SN2 reactions, so we can start by saying that methyl bromide > n-butyl bromide > cyclohexyl bromide. But how do the other two fit into the scale? An adjacent carbonyl group accelerates SN2 reactions enormously, so the ketone will react even faster than methyl bromide. On the other hand, a bulky tert-butyl group adjacent to a reaction centre leads to very slow substitution, so this compound (‘neopentyl bromide’) goes at the bottom of the scale.
BrMe Br Br
O
Br
Br
> > > >
adjacent C=O methyl primary secondary 'neopentyl'
� The summary table on p. 347 of the textbook might be useful revision here.
4. Qual dos compostos em cada par reage mais
rapidamente em uma reação do tipo SN1. Explique a
sua resposta.
(a)
Cl
Cl (b)
Br Br
(c)
Cl Cl
(d)
Cl OTs
5. Considere a seguinte reação:
Br CN
NaBrNaCN
DMSO+
a) Como a velocidade da reação será afetada se
a concentraçãoo de haloalcano for duplicada?
b) Como a velocidade da reação será afetada se
a concentraçãoo de NaCN for duplicada?
6. Considere a seguinte reação:
H2OHBr
OH Br+
a) Como a velocidade da reação será afetada se
a concentração de álcool for duplicada?
b) Como a velocidade da reação será afetada se
a concentração de HBr for duplicada?
7. Classifique cada um dos seguintes solventes como
prótico ou aprótico.
a) DMF b) Etanol c) DMSO
d) Água e) Amônia
8. Quando o álcool oticamente ativo abaixo é tratado
com HBr, uma mistura racêmica de brometos de alquila
é obtida:
336 CHAPTER 7 Substitution Reactions
(a) Assign the configuration of the chirality center in the substrate.
(b) Assign the configuration of the chirality center in the product.
(c) Does this SN2 process proceed with inversion of configuration? Explain.
7.46 Draw the transition state for the reaction between ethyl iodide and sodium acetate (CH3CO2Na).
7.47 (S)-2-Iodopentane undergoes racemization in a solution of sodium iodide in DMSO. Explain.
7.48 When the following optically active alcohol is treated with HBr, a racemic mixture of alkyl bromides is obtained:
HBrH2O
OH Br
Racemic mixture
+
Draw the mechanism of the reaction, and explain the stereochemical outcome.
7.49 (R)-2-Pentanol racemizes when placed in dilute sulfuric acid. Draw a mechanism that explains this stereochemical outcome, and draw an energy diagram of the process.
7.50 List the following carbocations in order of increasing stability:
!!
!!
7.51 Draw the carbocation intermediate that would be formed if each of the following substrates would participate in an SN1 reaction. In each case, identify the carbocation as being primary, secondary, or tertiary.
(a) Cl (b) Br (c) I (d) Cl
7.52 Propose a mechanism for the following transformation:
OH
H2OHCl
Cl
+
7.53 Draw the mechanism of the following reaction:
NaBrBr O
O
ONa
O
+
7.54 Each of the following reactions proceeds via an SN1 mechanism and will have anywhere from two to five steps, as discussed in Section 7.6. Determine the number of steps for each reaction and then draw the mechanism in each case:
(a) HClMeOH
Cl OMe
+
(b) NaClNaSH
Cl SH
+
(c) H2OHI
OH
+I
(d) OTs
TsOHEtOH
OEt+
7.55 Identify the product(s) in each of the following reactions:
(a)
EtOHBr
? (b) OTs
NaBr ?
(c)
OHHCl ?
(d)
NaCNDMSO ?
7.56 Identify the product of the following reaction:
NaOONa
BrBr
C4H8O2 2 NaBr+
7.57 The following reaction is very slow. Identify the mechanism and explain why the reaction is so slow.
BrNaOH
OHH2O
7.58 The following reaction is very slow:
Br OHHBr
H2O+
(a) Identify the mechanism.
(b) Explain why the reaction is so slow.
(c) When hydroxide is used instead of water, the reaction is very rapid. Draw the mechanism of this reaction and explain why it is so fast.
7.59 Identify the reagents you would use to achieve each of the fol-lowing transformations:
(a) OTs OH
(b) OH CN
(c) OH Br
(d)
Cl SH
(e)
O
O
Br
7.60 Each of the following compounds can be prepared with an alkyl iodide and a suitable nucleophile. In each case, identify the alkyl iodide and the nucleophile that you would use.
(a) OH (b) O
O
(c)
CN
(d) SH
(e)
OH
(f )
SH
Escreva o mecanismo da reação e explique o resultado
estereoquímico.
9. Proponha um mecanismo para as seguintes
transformações:
(a)
336 CHAPTER 7 Substitution Reactions
(a) Assign the configuration of the chirality center in the substrate.
(b) Assign the configuration of the chirality center in the product.
(c) Does this SN2 process proceed with inversion of configuration? Explain.
7.46 Draw the transition state for the reaction between ethyl iodide and sodium acetate (CH3CO2Na).
7.47 (S)-2-Iodopentane undergoes racemization in a solution of sodium iodide in DMSO. Explain.
7.48 When the following optically active alcohol is treated with HBr, a racemic mixture of alkyl bromides is obtained:
HBrH2O
OH Br
Racemic mixture
+
Draw the mechanism of the reaction, and explain the stereochemical outcome.
7.49 (R)-2-Pentanol racemizes when placed in dilute sulfuric acid. Draw a mechanism that explains this stereochemical outcome, and draw an energy diagram of the process.
7.50 List the following carbocations in order of increasing stability:
!!
!!
7.51 Draw the carbocation intermediate that would be formed if each of the following substrates would participate in an SN1 reaction. In each case, identify the carbocation as being primary, secondary, or tertiary.
(a) Cl (b) Br (c) I (d) Cl
7.52 Propose a mechanism for the following transformation:
OH
H2OHCl
Cl
+
7.53 Draw the mechanism of the following reaction:
NaBrBr O
O
ONa
O
+
7.54 Each of the following reactions proceeds via an SN1 mechanism and will have anywhere from two to five steps, as discussed in Section 7.6. Determine the number of steps for each reaction and then draw the mechanism in each case:
(a) HClMeOH
Cl OMe
+
(b) NaClNaSH
Cl SH
+
(c) H2OHI
OH
+I
(d) OTs
TsOHEtOH
OEt+
7.55 Identify the product(s) in each of the following reactions:
(a)
EtOHBr
? (b) OTs
NaBr ?
(c)
OHHCl ?
(d)
NaCNDMSO ?
7.56 Identify the product of the following reaction:
NaOONa
BrBr
C4H8O2 2 NaBr+
7.57 The following reaction is very slow. Identify the mechanism and explain why the reaction is so slow.
BrNaOH
OHH2O
7.58 The following reaction is very slow:
Br OHHBr
H2O+
(a) Identify the mechanism.
(b) Explain why the reaction is so slow.
(c) When hydroxide is used instead of water, the reaction is very rapid. Draw the mechanism of this reaction and explain why it is so fast.
7.59 Identify the reagents you would use to achieve each of the fol-lowing transformations:
(a) OTs OH
(b) OH CN
(c) OH Br
(d)
Cl SH
(e)
O
O
Br
7.60 Each of the following compounds can be prepared with an alkyl iodide and a suitable nucleophile. In each case, identify the alkyl iodide and the nucleophile that you would use.
(a) OH (b) O
O
(c)
CN
(d) SH
(e)
OH
(f )
SH
(b)
336 CHAPTER 7 Substitution Reactions
(a) Assign the configuration of the chirality center in the substrate.
(b) Assign the configuration of the chirality center in the product.
(c) Does this SN2 process proceed with inversion of configuration? Explain.
7.46 Draw the transition state for the reaction between ethyl iodide and sodium acetate (CH3CO2Na).
7.47 (S)-2-Iodopentane undergoes racemization in a solution of sodium iodide in DMSO. Explain.
7.48 When the following optically active alcohol is treated with HBr, a racemic mixture of alkyl bromides is obtained:
HBrH2O
OH Br
Racemic mixture
+
Draw the mechanism of the reaction, and explain the stereochemical outcome.
7.49 (R)-2-Pentanol racemizes when placed in dilute sulfuric acid. Draw a mechanism that explains this stereochemical outcome, and draw an energy diagram of the process.
7.50 List the following carbocations in order of increasing stability:
!!
!!
7.51 Draw the carbocation intermediate that would be formed if each of the following substrates would participate in an SN1 reaction. In each case, identify the carbocation as being primary, secondary, or tertiary.
(a) Cl (b) Br (c) I (d) Cl
7.52 Propose a mechanism for the following transformation:
OH
H2OHCl
Cl
+
7.53 Draw the mechanism of the following reaction:
NaBrBr O
O
ONa
O
+
7.54 Each of the following reactions proceeds via an SN1 mechanism and will have anywhere from two to five steps, as discussed in Section 7.6. Determine the number of steps for each reaction and then draw the mechanism in each case:
(a) HClMeOH
Cl OMe
+
(b) NaClNaSH
Cl SH
+
(c) H2OHI
OH
+I
(d) OTs
TsOHEtOH
OEt+
7.55 Identify the product(s) in each of the following reactions:
(a)
EtOHBr
? (b) OTs
NaBr ?
(c)
OHHCl ?
(d)
NaCNDMSO ?
7.56 Identify the product of the following reaction:
NaOONa
BrBr
C4H8O2 2 NaBr+
7.57 The following reaction is very slow. Identify the mechanism and explain why the reaction is so slow.
BrNaOH
OHH2O
7.58 The following reaction is very slow:
Br OHHBr
H2O+
(a) Identify the mechanism.
(b) Explain why the reaction is so slow.
(c) When hydroxide is used instead of water, the reaction is very rapid. Draw the mechanism of this reaction and explain why it is so fast.
7.59 Identify the reagents you would use to achieve each of the fol-lowing transformations:
(a) OTs OH
(b) OH CN
(c) OH Br
(d)
Cl SH
(e)
O
O
Br
7.60 Each of the following compounds can be prepared with an alkyl iodide and a suitable nucleophile. In each case, identify the alkyl iodide and the nucleophile that you would use.
(a) OH (b) O
O
(c)
CN
(d) SH
(e)
OH
(f )
SH
10. A reação abaixo é muito lenta:
336 CHAPTER 7 Substitution Reactions
(a) Assign the configuration of the chirality center in the substrate.
(b) Assign the configuration of the chirality center in the product.
(c) Does this SN2 process proceed with inversion of configuration? Explain.
7.46 Draw the transition state for the reaction between ethyl iodide and sodium acetate (CH3CO2Na).
7.47 (S)-2-Iodopentane undergoes racemization in a solution of sodium iodide in DMSO. Explain.
7.48 When the following optically active alcohol is treated with HBr, a racemic mixture of alkyl bromides is obtained:
HBrH2O
OH Br
Racemic mixture
+
Draw the mechanism of the reaction, and explain the stereochemical outcome.
7.49 (R)-2-Pentanol racemizes when placed in dilute sulfuric acid. Draw a mechanism that explains this stereochemical outcome, and draw an energy diagram of the process.
7.50 List the following carbocations in order of increasing stability:
!!
!!
7.51 Draw the carbocation intermediate that would be formed if each of the following substrates would participate in an SN1 reaction. In each case, identify the carbocation as being primary, secondary, or tertiary.
(a) Cl (b) Br (c) I (d) Cl
7.52 Propose a mechanism for the following transformation:
OH
H2OHCl
Cl
+
7.53 Draw the mechanism of the following reaction:
NaBrBr O
O
ONa
O
+
7.54 Each of the following reactions proceeds via an SN1 mechanism and will have anywhere from two to five steps, as discussed in Section 7.6. Determine the number of steps for each reaction and then draw the mechanism in each case:
(a) HClMeOH
Cl OMe
+
(b) NaClNaSH
Cl SH
+
(c) H2OHI
OH
+I
(d) OTs
TsOHEtOH
OEt+
7.55 Identify the product(s) in each of the following reactions:
(a)
EtOHBr
? (b) OTs
NaBr ?
(c)
OHHCl ?
(d)
NaCNDMSO ?
7.56 Identify the product of the following reaction:
NaOONa
BrBr
C4H8O2 2 NaBr+
7.57 The following reaction is very slow. Identify the mechanism and explain why the reaction is so slow.
BrNaOH
OHH2O
7.58 The following reaction is very slow:
Br OHHBr
H2O+
(a) Identify the mechanism.
(b) Explain why the reaction is so slow.
(c) When hydroxide is used instead of water, the reaction is very rapid. Draw the mechanism of this reaction and explain why it is so fast.
7.59 Identify the reagents you would use to achieve each of the fol-lowing transformations:
(a) OTs OH
(b) OH CN
(c) OH Br
(d)
Cl SH
(e)
O
O
Br
7.60 Each of the following compounds can be prepared with an alkyl iodide and a suitable nucleophile. In each case, identify the alkyl iodide and the nucleophile that you would use.
(a) OH (b) O
O
(c)
CN
(d) SH
(e)
OH
(f )
SH
a) Identifique o mecanismo.
b) Explique porque esta reação é lenta.
c) Quando hidróxido é usado no lugar de água a
reação é muito rápida. Escreva o mecanismo
desta reação e explique esse resultado.
2
11. Abaixo há dois métodos para preparar o mesmo
éter. Explique qual deles é o melhor.
ONa
O
NaOMe
CH3
12. Identifique o reagente que você usaria para fazer
as transformações abaixo.
a) álcool ciclobutílico a bromociclobutano
b) t-butanol a cloreto de tert-butila
e) cloroetano a etanol
13. Considere a seguinte reação SN2:
Br SH NaBrNaSHDMSO
+
a) Escreva o mecanismo detalhado.
b) Qual é a lei de velocidade desta reação?
c) O que acontece se o solvente for mudado
para EtOH?
d) Escreva o diagrama de energia desta reação,
apresentando a estrutura do estado de
transição, reagentes e produtos.
14. Considere a seguinte reação:
BrH2O
HBr
OH+
a) Escreva o mecanismo detalhado.
b) Qual é a lei de velocidade desta reação?
c) Essa reação seria mais rápida se NaBr fosse
adicionado?
d) Escreva o diagrama de energia desta reação,
apresentando a estrutura do estado de
transição, reagentes e produtos.
15. Sugira um mecanismo para a seguintes reações:
�
Suggested solutions for Chapter 15
PROB LEM 1 Suggest mechanisms for the following reactions, commenting on your choice of SN1 or SN2.
SOMe
O O
Br
PhSHNaOH
SO
O O
Br
Na
PhSMe
SOH
O O
BrOH
O
Purpose of the problem
Simple example of the two important mechanisms of chapter 15: SN1 and SN2.
Suggested solution
NaOH (pKa of water about 16) removes the proton from PhSH (pKa about 7) rapidly as this is a proton transfer between electronegative atoms. Clearly the methyl group must be transferred from O to S and this must be an SN2 reaction.
SO
O O
Br
Me SPh SN2 SO
O O
Br
+ PhSMe
The first reagent in the second reaction resembles the reagent in the first reaction but it is the free sulfonic acid and not the ester. The ether product must come from the displacement of OH from one molecule of t-BuOH by the OH group of the other and this can only be an SN1 reaction. The OH group leaves as H2O after being protonated by the sulfonic acid.
15
16. Prediga a estereoquímica dos produtos destas
reações.
Solutions for Chapter 15 – Nucleophilic substitution at saturated carbon 143
PROB LEM 7 Predict the stereochemistry of these products. Are they diastereoisomers, enantiomers, racemic or what?
Ph
O
NH
+
Ph
OH
N
OTs OTsH2SKOH
S
Purpose of the problem
Revision of stereochemistry from chapter 14 and practice at applying it to substitution reactions.
Suggested solution
The starting material in the first reaction has a plane of symmetry so it is achiral: the stereochemistry shows only which diastereoisomer we have. Attack by the amine nucleophile at either end of the epoxide (the two ends are the same) must take place from underneath for inversion to occur. The product is a single diastereoisomer but cannot, of course, be a single enantiomer so it doesn’t matter which enantiomer you have drawn. The stereochemistry of the Ph group cannot change—it is just a spectator.
Ph
O
NH
Ph
O
NH Ph
OH
N
The starting material for the second reaction is also achiral as it too has a plane of symmetry. The stereochemistry merely shows that the two OTs groups are on the same side of the molecule as drawn. Displacement with sulfur will occur with inversion and it is wise to redraw the intermediate before the cyclization. This ‘inverts’ the chiral centre so that we can see that the stereochemistry of the product has the methyl groups cis. There are various ways to draw this.
17. Considere a seguinte reação de substituição:
NaBr
Br CNNaCNDMSO
+
a) Escreva o mecanismo detalhado.
b) Qual é a lei de velocidade desta reação?
c) A reação acontece mais rapidamente se a
concentração de cianeto for dobrada?
d) Escreva o diagrama de energia desta reação,
apresentando a estrutura do estado de
transição, reagentes e produtos.
18. Quando a seguinte reação é tratada com iodeto de
lítio em DMF, um íon carboxilato é obtido. Escreva o
mecanismo desta reação. carboxylate ion is obtained:
O
OLiI
DMF
O
O Li@ ! +
Quando o éster metílico é usado como substrato, a
reação é 10 vezes mais rápida. Explique. times faster:
MeI
O
OLiI
DMF
O
O Li@ ! +
19. Quando (1R, 2R)-2-bromocicloexanol é tratado com
uma base forte, um epóxido é formado. Sugira um
mecanismo para essa transformação.
Br
OH
O
An epoxide
Strong base
3
20. Derivados halogenados de tolueno são hidrolisados
via um processo SN1.
Z
X Y
A velocidade de hidrólise depende de dois fatores: (a) a
estabilidade do grupo de partida e (b) a estabilidade do
carbocátion intermediário. Abaixo, a tabela apresenta
as velocidades de hidrólise (x 104 /min) para derivados
de tolueno e 30 ºC em uma mistura 50% acetona água
