QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride...
Transcript of QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride...
![Page 1: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/1.jpg)
Reação de Substituição Nucleofílica (SN2)
em sistemas biológicos
QFL-0342 Substituição nucleofílica
![Page 2: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/2.jpg)
Alkyl Halides and Nucleophilic Substitution
Nucleophilic substitution reactions in biological systems:
This reaction is called methylation because a CH3 group is transferred from
one compound (SAM) to another (:Nu¯).
![Page 3: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/3.jpg)
Tipos de reações ?
3
![Page 4: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/4.jpg)
Mecanismo
4
![Page 5: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/5.jpg)
5
Conversão de álcool em haletos de alquila
![Page 6: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/6.jpg)
6
Three components are necessary in any substitution reaction.
General Features of a Substitution Reaction
![Page 7: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/7.jpg)
Reações de Substituição Nucleofílica:
Dois tipos principais de mecanismos associados à
estrutura do material de partida
SN2 mechanism (one step)
![Page 8: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/8.jpg)
SN1 mechanism (2 steps)Rate = k [RX]
First order rate equation
![Page 9: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/9.jpg)
+ H2O +
+ other products
acetoneCH
3C CH
3
CH3
Br
CH3
C CH3
CH3
OH
H Br
![Page 10: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/10.jpg)
• The Reaction of tert-Butyl Chloride with
Hydroxide Ion: An SN1 Reaction
The rate is independent of hydroxide concentration and depends only on concentration
of tert-butyl chloride
SN1 reaction: Substitution, nucleophilic, 1st order (unimolecular)
– The rate depends only on the concentration of the alkyl halide
– Only the alkyl halide (and not the nucleophile) is involved in the transition state of
the step that controls the rate
![Page 11: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/11.jpg)
Energy Diagram for a SN1 reaction
![Page 12: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/12.jpg)
12
![Page 13: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/13.jpg)
![Page 14: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/14.jpg)
![Page 15: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/15.jpg)
Caracteristicas da reação de SN1
• Haletos terciários são altamente reativos;
• Aspecto central: estabilidade do carbócátion
![Page 16: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/16.jpg)
Estabilidade de carbocátions conjugados
(há dispersão da deficiência)
![Page 17: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/17.jpg)
Allylic and Benzylic Halides
• Allylic and benzylic intermediates stabilized by
delocalization of charge
– Primary allylic and benzylic are also more reactive in
the SN2 mechanism
![Page 18: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/18.jpg)
Exemplo de uma reação de SN1:Consequencias na estereoquímica dos
produtos
Mistura racêmica
![Page 19: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/19.jpg)
Consequencias estereoquímicas da formação de carbocátion
como intermediário nas reações de SN1: racemização
![Page 20: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/20.jpg)
Consequencias estereoquímicas da formação de carbocátion
como intermediário nas reações de SN1: racemização
![Page 21: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/21.jpg)
Efeito do solvente em SN1
• Stabilizing carbocation also stabilizes
associated transition state and controls rate
Solvation of a carbocation by water
![Page 22: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/22.jpg)
Solventes polares promovem a ionização e
estabilizam cátions formados
![Page 23: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/23.jpg)
Alkyl Halides and Nucleophilic Substitution
Nucleophilic substitution reactions in biological systems:
?
![Page 24: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/24.jpg)
Reações de Substituição Nucleofílica:
Dois tipos principais de mecanismos associados à
estrutura do material de partida
SN2 mechanism (one step)
![Page 25: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/25.jpg)
• Kinetics of a Nucleophilic Substitution
Reaction: An SN2 Reaction
![Page 26: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/26.jpg)
• An energy diagram of a typical SN2 reaction
![Page 27: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/27.jpg)
27
Effect of substrate structure on SN2 reaction
![Page 28: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/28.jpg)
Exemplo do efeito da estrutura do substrato sobre a
velocidade de reação via mecanismo SN2
![Page 29: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/29.jpg)
Quais seriam as diferenças nos níveis energéticos
dos estados de transição entre
RX metílico e um secundário?
![Page 30: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/30.jpg)
![Page 31: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/31.jpg)
Consequências estereoquímicas da SN2
![Page 32: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/32.jpg)
32
Consequências estereoquímicas da SN2
![Page 33: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/33.jpg)
Inversão de Walden (1896)
Ác. málico [a]D -2,3o
Ác. málico [a]D +2,3o Ác. (-)-clorosuccínico
Ác. (+)-clorosuccínico
P. Walden (1896). "Ueber die gegenseitige Umwandlung optischer Antipoden". Berichte der
deutschen chemischen Gesellschaft 29 (1): 133–138. doi:10.1002/cber.18960290127.
![Page 34: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/34.jpg)
Reação SN2 em sistemas cíclicos
![Page 35: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/35.jpg)
Efeito da Nucleofilicidade
• Nucleófilos básicos (aniônicos) são mais reativos do que oscorrespondentes neutros
![Page 36: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/36.jpg)
SN2 Reaction: nucleophilicity
Basicity Nucleophilicity
![Page 37: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/37.jpg)
![Page 38: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/38.jpg)
Ex of protic solvents:
![Page 39: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/39.jpg)
39
The Solvent
• Solvents that can donate hydrogen bonds (-OH or –NH) slow SN2 reactions by associating with reactants
• Energy is required to break interactions between reactant and solvent
• Polar aprotic solvents (no NH, OH, SH) form weaker interactions with substrate and permit faster reaction
![Page 40: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/40.jpg)
WWU -- Chemistry
SN2 Reaction: solvents
SN2 reactions are retarded (slowed) in polar, protic
solvents. Protic solvents have O-H groups.
Why are reactions retarded? Nucleophile is
hydrogen bonded to solvent!
Et O H O
Et
The nucleophile ishydrogen bondedto ethanol - reducesnucleophilicity
![Page 41: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/41.jpg)
41
• Polar aprotic solvents also exhibit dipole—dipole
interactions, but they have no O—H or N—H bonds. Thus,
they are incapable of hydrogen bonding.
Examples of polar aprotic solvents
![Page 42: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/42.jpg)
42
• Polar aprotic solvents solvate cations by ion—dipole interactions.
• Anions are not well solvated because the solvent cannot hydrogen bond
to them. These anions are said to be “naked”.
![Page 43: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/43.jpg)
![Page 44: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/44.jpg)
44
Estrutura do grupo abandonador
(leaving group)
H- (hidreto)
ou CH3- carbânion)
R-Nu +
Piores grupos
Abandonadores:
![Page 45: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/45.jpg)
45
Mecanismos
Not
good
LG
![Page 46: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/46.jpg)
Facilidade relativa de alguns gruposabandonadores:
LG
Bons
LG
ruins
Podem ser
sonvertidos
aos produtos
abaixo
![Page 47: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/47.jpg)
Mecanismo
47
![Page 48: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/48.jpg)
Como evitar os rearranjos ?
48
Adição de cloreto de zinco ou ácido de Lewis
![Page 49: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/49.jpg)
Reação de álcool com PBr3 ou
SOCl2
49
![Page 50: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/50.jpg)
50
![Page 51: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/51.jpg)
Mas como substituir ROH ?(converta-o em um bom LG)
S CH3
OR
O
O
S BrOR
O
O
para-Toluenesulfonate Tosylate
para-Bromobenzenesulfonate Brosylate
R OTs
R OBs
![Page 52: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/52.jpg)
Tosilatos, Mesilatos e triflatos:
grupos abandonadores derivados de
álcool
52
![Page 53: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/53.jpg)
Tosylate leaving group
(S)-(+)-1-Phenyl-2-propanol
(S)-(+)-1-Methyl-2-phenylethyl
tosylate
C2H5O
2-Ethoxy-1-phenylpropane
Is this ether (R) or (S)?
C OH
CH2
CH3
H
CH3
S Cl
O
O
C O
CH2
CH3
HTs
C O
CH2
CH3
HTs
CH2
CH O CH2
CH3
CH3_
+ H-Cl
Retention of configuration
Retention or inversion?
[Ts-Cl]
![Page 54: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/54.jpg)
Inversion of Configuration
CH2
CH
CH3
O S
O
O
CH3
CH2
CH3
CH2
O C
CH2
HCH
3
+ CH3
S O
O
O
(S)
(R)
_
O_ CH3
![Page 55: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/55.jpg)
Kenyon and Phillips 1920’s and 1930’s
Interprete o esquema abaixo:
![Page 56: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/56.jpg)
• Organic Synthesis: Functional Group Transformations
Using SN2 Reactions
![Page 57: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/57.jpg)
Formação de novas ligações
carbono-carbono via SN2
![Page 58: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/58.jpg)
Reação de alcoóis com bases:
preparação de alcóxidos
![Page 59: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/59.jpg)
Síntese de Williamson de éteres (SN2)
![Page 60: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/60.jpg)
![Page 61: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/61.jpg)
Quais seriam os produtos formados:
![Page 62: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/62.jpg)
62
• The strong nucleophile favors an SN2 mechanism.
• The weak nucleophile favors an SN1 mechanism.
![Page 63: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/63.jpg)
SN1 Reactions: some biological effects
R+: carbocátions - espécies altamente alquilantes que podem ser atacada
por biomoléculas como o DNA.
CH3Br
bromometano
CH3
SN2
![Page 64: QFL-0342 Substituição nucleofílica Reação de … 342...•The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S N 1 Reaction The rate is independent of hydroxide concentration](https://reader030.fdocuments.us/reader030/viewer/2022020412/5ad7ad577f8b9a9d5c8c64ed/html5/thumbnails/64.jpg)
Qual o mecanismo da SN envolvido na formação de terpenos?