chƯƠng 7 hoa lap the dong
TRANSCRIPT
-
8/13/2019 CHNG 7 Hoa lap the dong
1/47
L/O/G/O
CHNG 7:
HO HC LP TH NG
www.themegallery.com
Gio vin: ThS. Nguyn Th Kim An
-
8/13/2019 CHNG 7 Hoa lap the dong
2/47
www.themegallery.com
1. HIU NG LP TH
Hiu ng lp th l hiu ng do kch thc ln ca cc nguyn t haynhm nguyn t v do bin dng ca gc ho tr hay ca cc lin ktto nn. Hiu ng lp th c biu hin qua s cn tr khng gian,
qua sc cng gc ho tr hay lin kt lm nh hng n chiu hngv tin trnh lp th ca phn ng, n bn ca cc ng phn.
1.1. Khi nim:
1.2. Hiu ng khng gian loi I:
Hiu ng khng gian loi I l hiu ng gy ra bi cc nhm th c
kch thc tng i ln lm cn tr s tng tc ca tc nhn ivi tm phn ng hoc lm thay i hiu s nng lng t do giaphn t v trng thi chuyn tip.
-
8/13/2019 CHNG 7 Hoa lap the dong
3/47
-
8/13/2019 CHNG 7 Hoa lap the dong
4/47
www.themegallery.com
1.2.1. nh hng ca hiu ng khng gian loi mt n phn nglng phn t:
Khi trung tm phn ng ca phn t c nhng nguyn t hoc nhmnguyn t c kch thc ln th s lm cn tr hng tn cng ca cctc nhn phn ng vo trung tm phn ng v do lm gim kh
nng phn ng. S n ng khng gian ca cc nhm th cn tu thucvo hng tn cng ca tc nhn: t pha trc, t pha sau hocthng gc vi trung tm phn ng.- Kiu tn cng t pha sau c th thy r trong phn ng thnucleophin SN2. V d phn ng iu ch ete t ancolat v dn xuthalogen:
RO- + X RO + X-
-
8/13/2019 CHNG 7 Hoa lap the dong
5/47
www.themegallery.com
Khi kch thc ca gc ankyl trong dn xut halogen tng s gy rahiu ng khng gian loi I ln lm gim kh nng phn ng.V d: Kh nng phn ng iot ho cc ankyl bromua gim theo th tsau:
H X
H
H
> H3C X
H
H
H3C X
CH3
H
> > H3C X
CH3
CH3
kt 145,0 1,0 0,0078 0,0005
- Kiutncng tpha trctrongphnngtomuicaaminhoc tophc capiriin. V d tnh baz gim theo th tsau:
H2C
H2C
H2C
CH2
NH
H3C
H3C
H2C
CH2
NH
H3C CH2
NH2CH3C
CH2H3C
pKb 2,7 3,0 3,3
-
8/13/2019 CHNG 7 Hoa lap the dong
6/47
www.themegallery.com
- Phn ng cng vo nhm cacbonyl, tc nhn tn cng theo kiu thnggc vi mt phng ca lin kt C=O. Thc nghim cho thy hiu sut ca
phn ng gim i khi hiu ng khng gian loi I ca cc nhm th tng.1.2.2. nhhngcahiungkhng gian loiI nphnngnphn t:
Nhng phn ng n phn t nh phn ng th nucleophin SN
1, phnng tch E1 u qua giai on to thnh cacbocation trung gian:
Trong trng hp ny nu kch thc cc nhm th phn t cha phnng cng ln th phn ng xy ra cng d. Nguyn nhn: T cht ban un cacbocation trung gian s cc nhm th gim i, sc cng gc sgim i nn kh nng phn ng cng tng khi th tch cc nhm th cngtng. Hiu ng ny gi l hiu ng thay i cm cc nhm th c li.
X + X-
-
8/13/2019 CHNG 7 Hoa lap the dong
7/47
www.themegallery.com
1.2.3. nh hng ca hiu ng khng gian loi I n bn cang phn:Hiu ng khng gian loi I khng nhng c nh hng n kh nng
phn ng m cn nh hng n bn tng i ca cc ng phnhnh hc v ng phn cu dng. Khi tp trung nhiu nguyn t hoc
nhm nguyn t c th tch ln s lm gim tnh bn ca ng phnhnh hc cng nh ng phn cu dng.
1.3. Hiu ng khng gian loi II:Hiu ng khng gian loi II l hiu ng gy ra bi cc nhm c kchthc ln vi phm n tnh song song ca trc cc obitan p trong h linhp lm cho hiu ng lin hp mt tc dng, thay i tnh cht ca phnt.
V d:Cht Phenol p-nitrophenol 3,5-imetyl-4-nitrophenolpKa 10,0 7,2 8,2
-
8/13/2019 CHNG 7 Hoa lap the dong
8/47
www.themegallery.com
1.4. Hiu ng k hay hiu ng anchime:
Hiu ng k l mt loi hiu ng khng gian, xut hin khi trong phn tc nguyn t Z cn c nhng cp electron t do n ng gn trung tmphn ng mt khong cch cn thit (cch tm phn ng 2, 3, 4 nguyn t) c th to ra hp cht vng trung gian (vng oni, vngsunfoni, vng amoni)
C CZ
XC C
Z
+ X-
Nhm -Z ny c kh nng tn cng vo tm phn ng trc khi tc nhn Ytc dng lm cho trung tm phn ng b n ng khng gian pha c vng,
nh hng n cu hnh ca sn phm.Nhng nguyn t c cha cc cp electron (cc lin kt i hoc nhnthm) cng c kh nng to ra cacbocation vng.
+ X-C CC C
X
-
8/13/2019 CHNG 7 Hoa lap the dong
9/47
www.themegallery.com
Hiu ng k c nh hng n lp th ca phn ng nh dn n hin tng
raxemic ho, bo ton cu hnh v c th gy ra hin tng chuyn trung tm phnng t v tr ny sang v tr khc.V d: Thu phn axit -brompropionic hot ng quang hc trong mi trngkim:
O
Br
H
CH3O
O
H
CH3O
OH-
OOH
H
CH3O
(a) (b) (c)Phn ng xy ra theo c ch SN1, giai on chm nht l giai on to ra
cacbocation (b). cacbocation ny do tng tc ca oxi trong nhm cacboxylatvo cacbon mang in dng to ra trng thi chuyn tip vng n ng mt phn
khng gian, nn giai on nhanh ca qu trnh l s tn cng ca OH - vo phathun li hn v mt khng gian to ra axit lactic c cng cu hnh vi axit -brompropionic.
T s trn ta thy s tng tc ca nhm th bn cnh vi cacbon trung tm lqu trnh SN2 ni phn t, do c hiu ng k th nhm th bn cnh phi
v tr transoit i vi nhm b th X.
-
8/13/2019 CHNG 7 Hoa lap the dong
10/47
www.themegallery.com
Hiu ng k cng xy ra vi nhm k l nhm halogen. V d inhnh l phn ng gia 3-brombutan-2-ol vi hirobromua thnh2,3-ibrom theo c ch SN1.
CH3CHBrCHCH3
OH
HBr
-Br
- CH3CHBrCHCH3
OH2-H2O
CH3CHBrCHCH3Br- CH3CHBrCHBrCH3
Khi , t cp ng phn D,L-threo A s thu c cp ng phnD,L-threo B v t cp ng phn D,L-erythro A s thu c ng
phn meso v cacbocation to ra b tm chim bi nguyn t brom
k bn to thnh vng ion bromoni:
-
8/13/2019 CHNG 7 Hoa lap the dong
11/47
www.themegallery.com
H
OH2
CH3
CH3
Br
HH CH3
CH3
Br
H- H2O
Br-H
Br
CH3
CH3
Br
H
+CH3
Br
HH
Br
CH3
(+)-threo A khng quang ho t (+)-threo B (-)-threo B
H3C
OH2
H
CH3
Br
H
H3C HCH3
Br
H- H
2
O
Br-H3C
Br
H
CH3
Br
H
CH3
Br
HH3C
Br
H
(+)-erythro A' quang ho t meso B'
-
8/13/2019 CHNG 7 Hoa lap the dong
12/47
www.themegallery.com
1.5. Quy tc c nh cu dng trong phn ng tch lng phn t:
C ch tch E2 ch xy ra thun li khi bn tm tham gia phn ngphi nm trong cng mt phng, ngha l cc nguyn t, nhm nguynt tham gia phn ng phi v tr trans (anti) i vi nhau.
V d:
1.5.1. Quy tc Ingold: p dng cho cc hp cht mch h
-
8/13/2019 CHNG 7 Hoa lap the dong
13/47
www.themegallery.com
S tch trans c gii thch bi s thun li v mt nng lnghnh thnh trng thi chuyn tip do trnh c tng tc ca bazRO- v nguyn t Br c m in ln v s chuyn ho t Csp3sang Csp2 khng phi i hng obitan.
-
8/13/2019 CHNG 7 Hoa lap the dong
14/47
-
8/13/2019 CHNG 7 Hoa lap the dong
15/47
www.themegallery.com
1.5.3. Quy tc Endo: Quy tc xen ph cc i
Trong phn ng cng Diels Alder hai phn t ien v ienophinc sp xp trn hai mt phng song song v cc phn t nhhng cc nhm khng no ca phn t ienophin quay v phacc lin kt i ca ien hnh thnh trng thi chuyn tip dngvng.
V d: Anhirit maleic cng vo xiclopenta-1,3-ien nh sau:
O
O
O
O
O
OO
O
OO
O
O
-
8/13/2019 CHNG 7 Hoa lap the dong
16/47
www.themegallery.com
1.6. Hiu ng octo:
Hiu ng octo xy ra cc hp cht thm, y l hn hp cc hiung lp th loi I, loi II, hiu ng cm ng, hiu ng trng, linkt hiro
V d: o-R-C6H4-NH2 c tnh baz nh hn cc ng phn metav para.
1.7. Hiu ng cu dng:
Sc cng Baeyer gii thch km bn ca vng 3 cnh v 4 cnh.
-
8/13/2019 CHNG 7 Hoa lap the dong
17/47
www.themegallery.com
1.8. Hiu ng qua nhn hay hiu ng xuyn vng:Hiu ng qua nhn l hiu ng khng gian xut hin khi hai trungtm phn ng i din nhau trong vng nhng li gn nhau trongkhng gian do cu trc ca vng nn c th phn ng vi nhau
ni hoc chuyn lin kt qua vng. V d:
N
C
N
H+
O
CH3 CH3
OH
-
8/13/2019 CHNG 7 Hoa lap the dong
18/47
www.themegallery.com
2. HO LP TH CA PHN NG HU C
2.1. Phn ng th:Phn ng th l phn ng trong mt nguyn t hay nhm
nguyn t trong phn t hu c c thay th bng mt nguyn t haynhm nguyn t khc.
Phn ng tng qut:
Y + C X Y C + X-
-
8/13/2019 CHNG 7 Hoa lap the dong
19/47
www.themegallery.com
2.1.1. Phn ng th nucleophin: SN1 v SN2
a) Phn ng th SN2c km theo s quay cu hnh ca trung tmphn ng qua trng thi chuyn tip trung gian.
trng thi chuyn tip, tc nhn tng tc vi trung tm bt ikhi lin kt gia trung tm bt i vi nhm th cha b t honton. Khi ny nhm th v nhm b th c sp xp trn mt ngthng hai pha i vi trung tm bt i.
-
8/13/2019 CHNG 7 Hoa lap the dong
20/47
www.themegallery.com
Sau khi trng thi chuyn tip hnh thnh, nhm b th tch ra vcc lin kt C-R chuyn sang pha trc kia c nhm th X. Sn phmthu c c cu to t din ngc vi t din ban u. gi l snghch o Walden.
Nh vy, s nghch o Walden l s o ngc cu hnh ca sn
phm so vi cht ban u sau khi thc hin phn ng SN2 nguynt C bt i.
V d: Phn ng th ca 2R-brombutan nh sau:
-
8/13/2019 CHNG 7 Hoa lap the dong
21/47
www.themegallery.com
b) Phn ng SN1:
Phn ng SN1 xy ra vi s raxemic ho hoc quay cu hnh mtphn.
C ch phn ng xy ra qua hai giai on:
- Giai on 1: to ra cacbocation (y l giai on chm quyt nh tc phn ng).
- Giai on 2: tc nhn Y- tn cng vo cacbocation to thnh sn
phm cng (nhanh).
-
8/13/2019 CHNG 7 Hoa lap the dong
22/47
www.themegallery.com
-
8/13/2019 CHNG 7 Hoa lap the dong
23/47
www.themegallery.com
Thc t trong a s trng hp song song vi s raxemic ho c s
quay cu hnh mt phn. iu ny c gii thch l do anion X-chn mt phn ng tn cng ca tc nhn Nu-vo cacbocation phng,do buc Nu-phi u tin tn cng vo pha i din ging nhhng th theo c ch SN2.
Nh vy, nu thi gian tn ti ca cacbocation cng t, cacbocationcng mau chng phn ng vi tc nhn Nu-, trong khi X-cha kp ira xa khi trung tm phn ng th phn trm quay cu hnh cng ln.
Ngc li, thi gian tn ti ca cacbocation cng ln th phn trm
raxemic ho cng nhiu.
-
8/13/2019 CHNG 7 Hoa lap the dong
24/47
www.themegallery.com
Nhng do nh hng ca dung mi, phn ng SN1 thng xy ravi hn hp sn phm c cu hnh nghch chuyn cao hn.V d: S thu phn ca (1-cloetyl)benzen:
Cl
Ph
H3C
H
+ H2OCH3
H PhH2O Cl HO H
CH3
Ph(S)
- HCl
+ H2O - HCl
CH3
H Ph
H2O OH2
OH
Ph
H3C
H
HO
H
CH3
Ph
10%
90%
-
8/13/2019 CHNG 7 Hoa lap the dong
25/47
www.themegallery.com
Cu trc ca cht u vi c ch phn ng th nhm X trongphn t R X:
-Nu X gn trc tip vi C bc 1 phn ng xy ra ch yu theo cch SN2.
-Nu X gn trc tip vi C bc 3 phn ng xy ra ch yu theo cch SN1.-Nu X gn trc tip vi C bc 2, phn ng xy ra theo c ch
SN1 hoc SN2 ph thuc yu t cu trc hoc dung mi. Dung mi phncc lm cho phn ng xy ra theo c ch SN1, dung mi khng phn
cc hoc t phn cc lm cho phn ng xy ra theo c ch SN2.
-
8/13/2019 CHNG 7 Hoa lap the dong
26/47
www.themegallery.com
2.1.2. Phn ng th nucleophin ni phn t SNi :Phn ng th SNi cho sn phm c cu hnh ging ban u. Khi
cho mt ancol tc dng vi clorua tionyl SOCl2, phn ng qua giaion trung gian clorosunfit ankyl, c th c lp c, sau nhit
phn clorosunfit ankyl ta c cloruaankyl.
OH
R3
R1
R2
S O
Cl
Cl
- HCl+
O
R3
R1
R2 S
Cl
O
to Cl
R3
R1
R2
-
8/13/2019 CHNG 7 Hoa lap the dong
27/47
www.themegallery.com
V d:
-
8/13/2019 CHNG 7 Hoa lap the dong
28/47
www.themegallery.com
2.1.3. Phn ng th gc SR:
Phn ng th theo c ch gc l phn ng dy chuyn c ba giaion:- Giai on khi mo.- Giai on pht trin mch v to sn phm.
- Giai on tt mch v kt thc phn ng.V d phn ng clo ho ankan xy ra nh sau:- Giai on khi mo:- Giai on pht trin mch:
- Giai on tt mch v kt thc phn ng:
Giai on quyt nh tc phn ng l giai on pht trin mch.Cl - ClCl+Cl
R + R R - R
Cl - Cl Cl + Cl
Cl+R - H R + HCl
Cl+R - ClR + Cl2
-
8/13/2019 CHNG 7 Hoa lap the dong
29/47
www.themegallery.com
Phn ng th gc i qua gc t do trung gian, m gc t doc c cu phng, obitan cha mt electron c thn c trc ixng vung gc vi mt phng trn. Nn tc nhn c th tn cngvo tm phn ng t hai pha vi xc sut bng nhau cho ta hn
hp raxemic.
-
8/13/2019 CHNG 7 Hoa lap the dong
30/47
www.themegallery.com
2.2. Phn ng tch: E
Phn ng tch loi l phn ng m trong hai nguyn t haynhm nguyn t b tch ra khi phn t hu c v khng c nguyn thay nhm nguyn t no thay th vo.
V d:
CH3-CH2-OH CH2=CH2+ H2OPhn ng tch loi to lin kt i xy ra theo hai c ch: c ch
lng phn t E2 v c ch n phn t E1.
CSOH o
180,42
-
8/13/2019 CHNG 7 Hoa lap the dong
31/47
www.themegallery.com
2.2.1. Phn ng tch E2:
Phn ng tch E2 c c th lp th cao. Phn ng tch E2 xy rad dng nu phn t cht phn ng c th quay t do bn tm thamgia phn ng nm trn mt mt phng, ngha l v tr trans i vinhau v lin kt trc to iu kin thun li cho s xen ph cc i
cc obitan trong qu trnh hnh thnh lin kt.V d:
-
8/13/2019 CHNG 7 Hoa lap the dong
32/47
www.themegallery.com
Tch HX trn dn xut halogen:- ng phn erythro cho anken cis
- ng phn threo cho anken trans
H
H3C Ph
Br
PhH
H3C Ph
PhH
+ HBrNaOH/EtOH, to
E2
erythro cis
H
Ph CH3Br
PhH
Ph CH3
PhH
+ HBrNaOH/EtOH, to
E2
threo trans
-
8/13/2019 CHNG 7 Hoa lap the dong
33/47
www.themegallery.com
Tch halogen X2:- ng phn erythro cho anken trans
- ng phn threo cho anken cis
Br
H CH3
Br
HH3C
H CH3
HH3C
+ Br2axeton
E2
erythro trans
Br
H CH3
Br
CH3H
H CH3
CH3H
+ Br2axeton
E2
threo cis
-
8/13/2019 CHNG 7 Hoa lap the dong
34/47
www.themegallery.com
Phn ng tch E2 trn hp cht vng no:
Theo quy tc Barton, cc nhm b tch v tr trans v lin kt trc.
-
8/13/2019 CHNG 7 Hoa lap the dong
35/47
www.themegallery.com
2.3. Phn ng cng:
2.3.1. Phn ng cng electrophin: AE
2.3.1.1. Cng halogen X2:
Phn ng cng halogen vo anken din ra theo c ch cngelectrophin v quy tc cng trans. Cu hnh ca sn phm thu csau phn ng ph thuc vo cu hnh ca anken ban u v iu kin
tin hnh phn ng.
-
8/13/2019 CHNG 7 Hoa lap the dong
36/47
www.themegallery.com
C ch cng halogen vo anken c m t di y:
Trong c ch cng halogen ca anken c ba im quan trng:- Phn t halogen khng tc dng ng thi m b phn cc do tc dng ca
lin kt , tn cng vo anken theo hai giai on.- Giai on chm quyt nh tc chung ca phn ng l giai on tn cngca phn mang in dng vo ni i to ra tiu phn trung gian.- Trng thi chuyn tip vng ba cnh n ng mt pha khng gian, do ionX- tn cng vo anken t pha i din, tc l cng anti (cng t hai pha i
nhau).
-
8/13/2019 CHNG 7 Hoa lap the dong
37/47
www.themegallery.com
Kt qu khi cng halogen vo anken c cu hnh cis thu csn phm l cp D,L threo, cn khi cng halogen vo anken c cuhnh trans thu c sn phm c cu hnh D,L - erythro.
-
8/13/2019 CHNG 7 Hoa lap the dong
38/47
www.themegallery.com
Nu anken c hai nhm th ging nhau th t ng phn trans chthu c sn phm l ng phn meso.
-
8/13/2019 CHNG 7 Hoa lap the dong
39/47
www.themegallery.com
V d phn ng ca but-2-en vi dung dch Br2nh sau:
-
8/13/2019 CHNG 7 Hoa lap the dong
40/47
www.themegallery.com
Hoc phn ng ca axit maleic v axit fumaric vi dung dch Br2:
-
8/13/2019 CHNG 7 Hoa lap the dong
41/47
www.themegallery.com
Cu hnh ca sn phm sinh ra cn ph thuc vo dung mi tin
hnh phn ng. V d, thc nghim cho thy rng trong dung mi tphn cc, cis-stinben cng vi Br2 cho sn phm l hn hp raxemic;nhng trong cc dung mi phn cc (c hng s in mi ln hn 35)c cis-stinben v trans-stinben khi cng Br2u cho sn phm l ng
phn meso.
-
8/13/2019 CHNG 7 Hoa lap the dong
42/47
www.themegallery.com
2.3.1.2. Phn ng cng HX:
C ch ca phn ng c m t nh sau:
Phn ng cng hp cc axit halogenhiric vo anken ni chung xyra theo c ch cng trans, tr mt s trng hp tun theo quy tccng cis.
-
8/13/2019 CHNG 7 Hoa lap the dong
43/47
www.themegallery.com
Lp th ca phn ng trong trng hp ny c gii thch bng vic
hnh thnh ion protoni.
giai on tip theo anion X- tn cng vo pha i din vi pha cmt proton.Vi ankin, phn ng cng hp HX c th din ra theo kiu cis hoc
trans ph thuc vo dung mi v iu kin tin hnh phn ng.
+ H+ H
-
8/13/2019 CHNG 7 Hoa lap the dong
44/47
www.themegallery.com
2.3.2. Phn ng cng nucleophin: AN
Phn ng cng nucleophin vo lin kt i C=O khng c cth lp th bi v d phn ng din ra theo c ch cng cis hay cngtrans th u thu c mt sn phm duy nht do s quay t do quanhlin kt n C-O.
Nh vy nu phn ng cng to ra sn phm c nguyn t C bt ith sn phm l hn hp raxemic.
-
8/13/2019 CHNG 7 Hoa lap the dong
45/47
www.themegallery.com
Nhng nu trong trng hp trong phn t c mt nguyn t C
bt i lin kt vi nhm C=O th phn ng cng s to ra hai ngphn quang hc khng i quang, trong c mt ng phn c utin hnh thnh. Cu hnh ca sn phm chnh c xc nh theo quytc Cram.
Ni dung quy tc Cram gm hai im chnh sau:- Hp cht cacbonyl khi phn ng s cu dng c nguyn t Oca nhm C=O nm gia hai nhm th c kch thc nh nht canguyn t C bt i bn cnh v nhm R hay nguyn t H ca nhmC=O nm v tr che khut vi nhm th ln nht ca C bt i .
- Sn phm u tin hnh thnh l sn phm do tc nhn nucleophintn cng vo pha t b n ng khng gian, tc l pha gia nhm nhnht v nhm ln nht.
MS O
-
8/13/2019 CHNG 7 Hoa lap the dong
46/47
www.themegallery.com
R
MS
L
O
L
RNu
OHMS
L
NuR
OHMS
Nu:
Sn phm chnh
Nu:
O MS
RL
Sn phm ph
-
8/13/2019 CHNG 7 Hoa lap the dong
47/47