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


2/118

ALKYL HALIDE

C

X

H

H

Electrophilic carbon atom

Tm thn in t


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


4/118

SUBSTITUTIONorELIMINATION ?

C

Nu:

+X C

X:+Nu

C C

X

HNu:

CC

H

H

H

H

Nu H ++X:


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


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



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 tng


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 mnh hnTnh base yu hn

Tnh thn hch yu hnTnh base mnh hn


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


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



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



12/118


* nh hng ca dung mi


13/118


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


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


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


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


18/118

PHN NG TH THN HCH


19/118

PHN NGTH THN HCH SN2


20/118



21/118



22/118

CHT THN HCH


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


24/118

NHM XUT


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


26/118

C

H

HH

Br

C

H3C

H3C

H

Br

C

H3C

HH

Br

C

H3C

H3C

H3C

Br


27/118


28/118

KHNNGBN VNGHA

TRNG THI CHUYN TIP

CHNGNGI LP TH

CU TRCALKYLHALIDE


29/118


30/118


31/118


32/118


33/118


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.


35/118


36/118

CC

Cl

RR

R

Nu:

Vin l hali e

X No reaction

Cl

:Nu

X No reaction

Ar l hali e


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.


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


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)


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


41/118

YU T LP TH TRONG SN2

Sn phm to thnh cs o ngc cu hnhca nguyn t carbonso vi ban u


42/118

HH3C

H

Cl

OH

H

H

H3C

H

Cl

HHO:

cis-1-Chloro-3-methylcyclopentane

H3C

H

H

OHCl+

trans-3-methylcyclopentanol



43/118



44/118



45/118


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


47/118

TH THN HCH SN1


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


49/118


50/118

KH NNG BN VNG HA

ION CARBOCATION

KHNG NH HNG BI

CHNGNGI LPTH

CU TRCALKYLHALIDE


51/118


52/118

ALKYL CARBOCATION


53/118

ALKYL CARBOCATION


54/118

ALKYL CARBOCATION


55/118

ALLYLIC CARBOCATION


56/118

BENZYLIC CARBOCATION


57/118

Khng nhhng bi

chng ngilp th.


58/118



59/118



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


61/118


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


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


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.


65/118

SN1 OR SN2 ???


66/118


67/118

Sn phm ca (a) l ng phn ca sn

phm (b). Phn ng SN1 Hay SN2 ?


68/118

Sp xp cc ng phn c

cng CTPT C4H9Cl theo

chiu gim dn hot tnhtrong phn ng vi sodium

iodide trong acetone?


69/118

Ha hc lp th ca A v B?


70/118

?

?


71/118

Ha hc lp th ca2-Bromobutane?


72/118

Vn tc phn ng tng khi dng

mt lng nh NaIlm xc tc.

Gii thch?

PHN NG TCH (KH)


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


74/118

bn ca Alkene


75/118

PHN NGTCH


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


77/118

Cn s dngBase mnh vnng base cao.

PHN NGTCH E2


78/118


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


80/118

YUT LPTH TRONG E2


81/118

YU T LP TH TRONG E2


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


83/118


84/118


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


86/118

YUT LPTH TRONG E2

Cyclohexyl halide: H v X u v traxial v l trans i vi nhau


87/118


88/118


89/118


90/118


91/118

PHN NG TCH E1


92/118

PHN NGTCH E1

Khngcn dngbase mnh


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


94/118


95/118


96/118

Phn ng Th hay Kh ?


97/118

Phn ng Th hay Kh?

Chng ngi lp th Tnh base

Nhit

CHNG NGILP TH


98/118

E2 hay SN2 ???


99/118

y N

E2 hay SN2 ???


100/118

y N

TNH BASE


101/118

TNH BASE

TNH BASE


102/118

TNH BASE

Nhi


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


104/118



105/118



106/118


S to thnh Tosylate


107/118

S to thnh Tosylate

Reagents: ROH + TsCl + Pyridine

S to thnh Mesylate


108/118

S to thnh Mesylate

Reagents: ROH + MsCl + Triethylamine


109/118


110/118

Sn Phm Chnh?


111/118

Sn Phm Chnh?

Sn Phm Chnh?


112/118

Sn Phm Chnh?

Sn Phm Chnh?


113/118

Sn Phm Chnh?


114/118

Sn Phm Chnh?

C h ?


115/118

C ch ?


116/118

C ch ?


117/118

C c ?


118/118

Co Che Phan Ung Huu Co Chuong 02

Documents

Transcript of Co Che Phan Ung Huu Co Chuong 02