Co Che Phan Ung Huu Co Chuong 02
Transcript of Co Che Phan Ung Huu Co Chuong 02
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
1/118
PHN NG
TH THN HCH& PHN NG KH
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
2/118
ALKYL HALIDE
C
X
H
H
Electrophilic carbon atom
Tm thn in t
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
3/118
The strengths of the carbon-
halogen bondsC-H 413 C-F 467
C-Cl 346
C-Br 290
C-I 228
Rates of reaction: RCl < RBr < RI
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
4/118
SUBSTITUTIONorELIMINATION ?
C
Nu:
+X C
X:+Nu
C C
X
HNu:
CC
H
H
H
H
Nu H ++X:
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
5/118
TNH THN HCH V TNH BASE
Nu :
(RO,2O, BrNH3,....)
Nucleophile
Base (Lewis)
Substitution
Elimination
Tnh thn hch
i lc i vi cht thn in t Tnh base
i lc i vi proton
Phn ng th
Phn ngtch
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
6/118
Cc cht thn hch c tm thn hch
l cc nguyn t ging nhau:
Tnh thn hch v tnh base bin isong song vi nhau.
V d: tnh base v tnh thn hch:
RO > HO >> RCO2 > R O H > H2O
TNH THN HCH V TNH BASE
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
7/118
Khi cc tm thn hch khc nhau* Trong cng mt chu k:
Cc ion cng in tch: tnh thn hch vtnh base bin thin song song vi nhau vcng gim dn t tri sang phi.
TNH THN HCH V TNH BASE
Tnh thn hch v tnh base tng
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
8/118
* Trong cng mt nhm:
Tnh base v tnh thn hch bin i
ngc vi nhau.S::
:
CH3
more ucleophilicless asic
O::
:
CH3
less ucleophilicmore asic
TNH THN HCH V TNH BASE
Tnh thn hch mnh hnTnh base yu hn
Tnh thn hch yu hnTnh base mnh hn
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
9/118
i creasi g ucleophilicitydecreasi g asicity
I:
:
:
Br:
:
:
Cl:
:
:
F:
:
:
T trn xung bn knh nguyn t tng
trong khi m in li gim.
Kh nng b solvat ha bi dung mi.
Tnh thn hch tng, tnh base gim
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
10/118
* nh hng ca in tch ion
Dng anion lun c tnh thnhch mnh hn dng phn t
V d: OH > H2O ; R O > ROH
TNH THN HCH V TNH BASE
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
11/118
* nh hng ca yu t lp th
Kch thc cng ln
Tnh thn hch cng yu
Tnh base cng mnh
Tnh base: (CH3)3CO > CH3CH2O
Tnh thn hch: (CH3)3CO < CH3CH2O
TNH THN HCH V TNH BASE
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
12/118
TNH THN HCH V TNH BASE
* nh hng ca dung mi
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
13/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
14/118
NHM XUT
c tch ra khi phn t di dng
phn t trung ha in hoc ion m.
Nhm xut tt: ion c kh nng bn
vng ha in tch m ca n: base yu
Tnh base: F >> Cl > Br > I
Kh nng xut: I > Br > Cl >> F
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
15/118
S
O
O
O R
S
O
O
O O
R
Alkanes lfonate ion Alk l s lfate ion
S
O
O
O CH3 S
O
O
O CF
F
F
p-Toluenesul onate ion Tri late ion
NHM XUT TT
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
16/118
Ion c tnh base mnh: OH , H, R
Nhm xut rt yu
X R OH X OHR X +
X R OH X H2OR X +
H
+
Nu XH+CH3CH2 H CH3CH2 Nu
Nu X
CH3+CH3 CH3 CH3 Nu
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
17/118
PHN NG TH THN HCH
(NUCLEOPHILIC SUBSTITUTION)
C X
Nu:
C Nu X:
+
Nu: Cht thn hch (Nucleophile)
X Nhm xut (Leaving group)
2 c ch: SN1 v SN2
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
18/118
PHN NG TH THN HCH
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
19/118
PHN NGTH THN HCH SN2
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
20/118
PHN NGTH THN HCH SN2
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
21/118
PHN NGTH THN HCH SN2
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
22/118
CHT THN HCH
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
23/118
Cht thn hch cng mnh, phn
ng xy ra cng nhanh
mnh tng i ca cc cht
thn hch:
CHT THN HCH
CH3Br + Nu:
CH3Nu + Br
Nu = HS > H2ONH3Cl
HOCH3OICN > > > > > >
H2O
C2H5OH
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
24/118
NHM XUT
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
25/118
Carbon mang nhm th cng knhp Cn tr tc kch ca cht thn hch
p Phn ng cng chm.
Alkyl halide bc 3: khng cho phn
ng th SN2.
Tng t, do chng ngi lp th,vinylic halide v aryl halide hon
ton khng cho phn ng th SN2.
CU TRCALKYLHALIDE
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
26/118
C
H
HH
Br
C
H3C
H3C
H
Br
C
H3C
HH
Br
C
H3C
H3C
H3C
Br
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
27/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
28/118
KHNNGBN VNGHA
TRNG THI CHUYN TIP
CHNGNGI LP TH
CU TRCALKYLHALIDE
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
29/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
30/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
31/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
32/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
33/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
34/118
Chng ngi lp th trong SN2 Methyl: CH3X: rt nhanh
Alkyl bc 1: RCH2X: nhanh
Alkyl 2: R2CHX: chm
Alkyl 3: R3CX: k.p.
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
35/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
36/118
CC
Cl
RR
R
Nu:
Vin l hali e
X No reaction
Cl
:Nu
X No reaction
Ar l hali e
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
37/118
nh hng ca dung mi
Dung mi phn cc Trong dung dch: cht thn hch v c
tp cht kch ng s b solvat ha:
Bn vng ha trng thi chuyn tip
Tng vn tc phn ng.
Cn tr s tip cn tm carbon thnin t ca cht thn hch
Gim tc phn ng th SN
2.
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
38/118
Protonic solvents
Kh nng solvate
ha mnh, c bit
vi cht thn hch
l anion t c s dng
X: H ORRO H
H
OR
HOR
nh hng ca dung mi
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
39/118
Dung mi trong phn ng SN2
Solvate ha tt cc cation kim loi Solvat ha rt km cc anion
C
O
H NCH3
CH3
: :
:
N,N-Dimeth l ormami e(DM )
S
O
H3C CH3
: :
:
Dimeth lsul oxi e(DMSO)
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
40/118
CH3C N
CH3
CH3
: :
:
Dimethylacetamide
(DM )
P
O
(CH3)2N N(CH3)2
: :
:
N(CH3)2
:
:
Hexamethylphosphoramide(HMP )
Dung mi trong phn ng SN2
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
41/118
YU T LP TH TRONG SN2
Sn phm to thnh cs o ngc cu hnhca nguyn t carbonso vi ban u
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
42/118
HH3C
H
Cl
OH
H
H
H3C
H
Cl
HHO:
cis-1-Chloro-3-methylcyclopentane
H3C
H
H
OHCl+
trans-3-methylcyclopentanol
YU T LP TH TRONG SN2
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
43/118
YU T LP TH TRONG SN2
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
44/118
YU T LP TH TRONG SN2
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
45/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
46/118
CH3C
CH3
CH3
Cl C
CH3
H3C
CH3
+ + ClSlow
H2O
Step 1
C
CH3
H3C
CH3
+Step 2 O H
H
::
+ast
CH3C
CH3
CH3
O H
H
+:
CH3C
CH3
CH3
O H
H
+: O H
H
::
+ast
CH3C
CH3
CH3
O:
H
:
O H
H
:
H++Step 3
TH THN HCH SN1
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
47/118
TH THN HCH SN1
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
48/118
Ch ph thuc vo bn cht v
nng Alkyl Halide Khng ph thuc vo bn cht
v nng ca cht thn hch
Tc phn ng th SN1
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
49/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
50/118
KH NNG BN VNG HA
ION CARBOCATION
KHNG NH HNG BI
CHNGNGI LPTH
CU TRCALKYLHALIDE
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
51/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
52/118
ALKYL CARBOCATION
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
53/118
ALKYL CARBOCATION
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
54/118
ALKYL CARBOCATION
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
55/118
ALLYLIC CARBOCATION
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
56/118
BENZYLIC CARBOCATION
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
57/118
Khng nhhng bi
chng ngilp th.
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
58/118
YU T LP TH TRONG SN1
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
59/118
YU T LP TH TRONG SN1
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
60/118
R1
R2R3
CC
R1
R2
R3
Nu Nu+
Nu
50% inversion ofconfi uration
50% retension ofconfi uration
lanar, achiral carbocationinterme iate
Chiral substrate
Dissociation
C Y
R1
R2
R3
C Nu
R1
R
2R3
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
61/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
62/118
Protic solvents: tng tc ionha ca alkyl halide
Tng vn tc phn ng th SN1
Nhng dung mi loi ny thng c
hng s in mi ln, tc c khnng tch mnh cc ion dng vm ra khi nhau.
nh hng ca dung mi
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
63/118
S CNH TRANH GIA SN1 v SN2
4 yu t quan trng
Cu trc ca tc cht Nng v mnh ca cht
thn hch
Dung mi Bn cht ca nhm xut
SN SN
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
64/118
SN1 SN2RX 3r Methyl > 1r > 2r
Nu: Base Lewis yu, ccphn t trung hahoc cc phn t
dung mi(s dung mi gii)
BaseLewis mnh,nng cao
Dungmi
Phn cc, c proton(ru, nc,)
Phn cc, khngc proton (DMF,DMSO,)
Nhm xut: nh hng nh nhau trong c hailoi phn ng: nhm xut cng tt khi n c
tnh base cn u.
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
65/118
SN1 OR SN2 ???
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
66/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
67/118
Sn phm ca (a) l ng phn ca sn
phm (b). Phn ng SN1 Hay SN2 ?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
68/118
Sp xp cc ng phn c
cng CTPT C4H9Cl theo
chiu gim dn hot tnhtrong phn ng vi sodium
iodide trong acetone?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
69/118
Ha hc lp th ca A v B?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
70/118
?
?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
71/118
Ha hc lp th ca2-Bromobutane?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
72/118
Vn tc phn ng tng khi dng
mt lng nh NaIlm xc tc.
Gii thch?
PHN NG TCH (KH)
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
73/118
PHN NG TCH (KH)(ELIMINATION REACTION)
Phn t b loi:HX ( ehy rohalo enha), nc ( ehy rat ha),
Quy tc Zaitsev: sn phm chnh tothnh s l alkene man nhiu nhmth nht
C
Y
C
Z
elimination
(
YZ)
CC
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
74/118
bn ca Alkene
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
75/118
PHN NGTCH
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
76/118
Hai c ch: Tch E1 v Tch E2
PHN NG TCH
CH3CH2CHCH3
CH3CH2CCH3
CH3
CH3CH2ONa+
CH3CH2OH2-Bromobutane
CH3CH!CHCH3 CH3CH2CH CH2
2-Butene (81%) 1-Butene (19%)
+
CH3CH2ONa+
CH3CH2OH
CH3CH!C(CH3)2 CH3CH2C CH2
2-Methyl-2-butene (70%) 2-Methyl-1-butene (30%)
+
2-Bromo-2-methylbutane
Br
Br CH3
PHN NG TCH E2
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
77/118
Cn s dngBase mnh vnng base cao.
PHN NGTCH E2
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
78/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
79/118
YUT LPTH TRONG E2
Nguyn t H, hai nguyn t C v nhm
xut X: anti periplanar
H
X
Anti periplanar
H
X
Anti transition state
B...
:
Alkene
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
80/118
YUT LPTH TRONG E2
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
81/118
YU T LP TH TRONG E2
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
82/118
YU T LP TH TRONG E2
CH3CH2CH2Br + tBuOK CH3CH=CH2tBuOH
H CH3
H
Br
H H
H3C H
H
H
HBr
H H
CH3
H
Br H
H3C
H
H
H Br
H
H
CH3
H
HBr
H
H
H
CH3
H
Br
H
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
83/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
84/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
85/118
YUT LPTH TRONG E2
C
Br
hH
KOH
EthanolC
H
Br h
B:C
hH
CBr h
H
Brh
hH
Br
hHBr
h
meso-1,2-Dibromo-1,2-diphenylethane (E)-1-Bromo-1,2-diphenylethylene
YU T LP TH TRONG E2
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
86/118
YUT LPTH TRONG E2
Cyclohexyl halide: H v X u v traxial v l trans i vi nhau
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
87/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
88/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
89/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
90/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
91/118
PHN NG TCH E1
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
92/118
PHN NGTCH E1
Khngcn dngbase mnh
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
93/118
Ch xy ra i vi nhng cht c
th ion ha to thnh carbocation
bn vng: Alkyl halide bc 3
Benzyl halide Allyl halide,
PHN NGTCH E1
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
94/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
95/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
96/118
Phn ng Th hay Kh ?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
97/118
Phn ng Th hay Kh?
Chng ngi lp th Tnh base
Nhit
CHNG NGILP TH
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
98/118
E2 hay SN2 ???
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
99/118
y N
E2 hay SN2 ???
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
100/118
y N
TNH BASE
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
101/118
TNH BASE
TNH BASE
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
102/118
TNH BASE
Nhi
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
103/118
Nhit
Phn ng tch: S > 0
G < 0 khi T cng ln
Phn ng tch cn nhit
Nhm xut trong E2 v E1
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
104/118
Nhm xut trong E2 v E1
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
105/118
Nhm xut trong E2 v E1
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
106/118
Nhm xut trong E2 v E1
S to thnh Tosylate
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
107/118
S to thnh Tosylate
Reagents: ROH + TsCl + Pyridine
S to thnh Mesylate
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
108/118
S to thnh Mesylate
Reagents: ROH + MsCl + Triethylamine
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
109/118
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
110/118
Sn Phm Chnh?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
111/118
Sn Phm Chnh?
Sn Phm Chnh?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
112/118
Sn Phm Chnh?
Sn Phm Chnh?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
113/118
Sn Phm Chnh?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
114/118
Sn Phm Chnh?
C h ?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
115/118
C ch ?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
116/118
C ch ?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
117/118
C c ?
-
8/6/2019 Co Che Phan Ung Huu Co Chuong 02
118/118