PH N & PH N

NG NG KH

TH THN H CH

ALKYL HALIDE
X H
H

Tm thn carbon Electrophilic i n t atom

The strengths of the carbonhalogen bonds

C-H 413 C-F C-Cl C-Br C-I 467 346 290 228

Rates of reaction: RCl < RBr < RI

SUBSTITUTION or ELIMINATION ?
Nu: Nu:
 

X H

C H C H C H +

Nu

X:

H C C X

Nu

 H + X:

TNH THN H CH V TNH BASE

Nucleophile Base (Lewis) Nu :
  

Substitution Ph n ng th

Ph n ng Elimination tch

(RO ,2O, Br NH3,....)

 Tnh thn h ch

i l c i v i ch t thn i n t  Tnh base i l c i v i proton

TNH THN H CH V TNH BASE

Cc ch t thn h ch c tm thn h ch l cc nguyn t gi ng nhau: Tnh thn h ch v tnh base bi n song song v i nhau. V d : tnh base v tnh thn h ch: RO > HO >> RCO2 > ROH > H2O i

TNH THN H CH V TNH BASE

Khi cc tm thn h ch khc nhau * Trong cng m t chu k : Cc ion cng i n tch: tnh thn h ch v tnh base bi n thin song song v i nhau v cng gi m d n t tri sang ph i.

Tnh thn h ch v tnh base t ng

TNH THN H CH V TNH BASE

* Trong cng m t nhm: Tnh base v tnh thn h ch bi n ng c v i nhau. i

Tnh thn h ch m nh h n Tnh thn h ch y u h n more y u h n ucleophilic Tnh baseucleophilic less m nh h n Tnh base

less asic

CH3

more asic

 S:

CH3

 O:

: :

: :

: :

 F:

 Cl:

 Br:

i creasi g ucleophilicity decreasi g asicity

 T trn xu ng bn knh nguyn t t ng
trong khi m i n l i gi m.

Tnh thn h ch t ng, tnh base gi m

 Kh n ng b solvat ha b i dung mi.

 I:

TNH THN H CH V TNH BASE * nh h ng c a i n tch ion D ng anion lun c tnh thn h ch m nh h n d ng phn t
V d : OH > H2O ; RO > ROH

TNH THN H CH V TNH BASE * nh h ng c a y u t l p th Kch th c cng l n Tnh thn h ch cng y u Tnh base cng m nh
Tnh base: (CH3)3CO > CH3CH2O Tnh thn h ch: (CH3)3CO < CH3CH2O

TNH THN H CH V TNH BASE

* nh h ng c a dung mi

NHM XU T
 c tch ra kh i phn t d i d ng

phn t trung ha i n ho c ion m.  Nhm xu t t t: ion c kh n ng b n v ng ha i n tch m c a n: base y u Tnh base: F >> Cl > Br  > I Kh n ng xu t: I > Br  > Cl >> F

NHM XU T T T
O
 O S R

O
 O S O R

O Alkanes lfonate ion

O

O Alk l s lfate ion

O CH3 F C F F

 O

S O

 O

S O

p-Toluenesul onate ion

Tri late ion

Ion c tnh base m nh: OH , H, R Nhm xu t r t y u

X X R OH R OH H
 Nu  Nu

X X

R X R X

+ +

OH  H2O

CH3CH2 CH3

H CH3

X X

CH3CH2 CH3

Nu

+
 CH3

Nu +

PH N

NG TH THN H CH

(NUCLEOPHILIC SUBSTITUTION)
Nu:


Nu

X:

Nu: Ch t thn h ch (Nucleophile) X Nhm xu t (Leaving group)

2 c ch : SN1 v SN2

PH N

NG TH THN H CH

PH N

NGTH THN H CH SN2

PH N

NGTH THN H CH SN2

PH N

NGTH THN H CH SN2

CH T THN H CH

CH T THN H CH
 Ch t thn h ch cng m nh, ph n

ng x y ra cng nhanh  m nh t ng i c a cc ch t thn h ch:

CH3Br Nu = + Nu :


H2 O C2H5OH

CH3Nu

Br NH3 > H2O

  HS > CN > I > CH3O > HO  > Cl >

NHM XU T

C U TRC ALKYL HALIDE

Carbon mang nhm th c ng k nh p C n tr tc kch c a ch t thn h ch p Ph n ng cng ch m. Alkyl halide b c 3: khng cho ph n ng th SN2. T ng t , do ch ng ng i l p th , vinylic halide v aryl halide hon ton khng cho ph n ng th SN2.

H H C H Br

H3C H C H Br

H3C H3C C H Br

H3C C H3C H3C Br

C U TRC ALKYL HALIDE

 KH N NG B N V NG HA
TR NG THI CHUY N TI P

 CH

NG NG I L P TH

Ch

ng ng i l p th trong SN2

Methyl: CH3X: r t nhanh Alkyl b c 1: RCH2X: nhanh Alkyl 2: R2CHX: ch m Alkyl 3: R3CX: k.p.

R C R C

Cl R

No reaction

Nu :

Vin l hali e
: Nu


Cl

No reaction

Ar l hali e

nh h

ng c a dung mi

Dung mi phn c c Trong dung d ch: ch t thn h ch v c t p ch t kch ng s b solvat ha: B n v ng ha tr ng thi chuy n ti p T ng v n t c ph n ng. C n tr s ti p c n tm carbon thn i n t c a ch t thn h ch Gi m t c ph n ng th SN2.

nh h

ng c a dung mi
OR H RO H X : H OR H OR

Protonic solvents Kh n ng solvate ha m nh, c bi t v i ch t thn h ch l anion t c s d ng

Dung mi trong ph n

ng SN2

 Solvate ha t t cc cation kim lo i  Solvat ha r t km cc anion

:

: O
:

CH3 N,N-Dimeth l ormami e (DM )

Dimeth lsul oxi e (DMSO)

H C N

CH3

: O
S CH3

H3C

Dung mi trong ph n
:
:

ng SN2
:
: O

H3C C N

CH3

CH3 Dimethylacetamide (DM )

(CH3)2N P N(CH3)2 : N(CH3)2 Hexamethylphosphoramide (HMP )

Y UT

L P TH TRONG SN2

S n ph m t o thnh c s o ng c c u hnh c a nguyn t carbon so v i ban u

Y UT
H3C H

L P TH TRONG SN2
H

Cl Cl H HO: H3C H
H OH

cis-1-Chloro-3-methylcyclopentane

H3C H

H + OH Cl

trans-3-methylcyclopentanol

Y UT

L P TH TRONG SN2

Y UT

L P TH TRONG SN2

TH THN H CH SN1
CH3 Step 1 H3C C CH3 CH3 Step 2 H3C C+ CH3 CH3 Step 3 H3C C O
+

Cl

Slow H2O

CH3 H3C C+ CH3 ast CH3 H3C C O+ H CH3 H ast CH3 H3C C O: + H O+ H CH3 H + Cl

:O H H

CH3 H

H + :O H H

:
H

TH THN H CH SN1

T c

ph n ng th SN1

 Ch ph thu c vo b n ch t v n ng v n ng Alkyl Halide c a ch t thn h ch  Khng ph thu c vo b n ch t

C U TRC ALKYL HALIDE

 KH N NG B N V NG HA ION CARBOCATION  KHNG CH NH H NG B I NG NG I L P TH

ALKYL CARBOCATION

ALKYL CARBOCATION

ALKYL CARBOCATION

ALLYLIC CARBOCATION

BENZYLIC CARBOCATION

Khng nh h ng b i ch ng ng i l p th .

Y UT

L P TH TRONG SN1

Y UT

L P TH TRONG SN1

R1

C
R2 R3

Chiral substrate

Dissociation
R1

R1

Nu Nu

Nu

R1

C
R2 R3

C
R2 R3 R2

C
R3

Nu

50% inversion of confi uration

lanar, achiral carbocation interme iate

50% retension of confi uration

nh h

ng c a dung mi
ion

Protic solvents: t ng t c ha c a alkyl halide

T ng v n t c ph n ng th SN1 Nh ng dung mi lo i ny th ng c h ng s i n mi l n, t c c kh n ng tch m nh cc ion d ng v m ra kh i nhau.

C NH TRANH GI A SN1 v SN2

4 y u t quan tr ng
 C u trc c a tc ch t  N ng v m nh c a ch t thn h ch  Dung mi  B n ch t c a nhm xu t

SN1
RX Nu: 3r Base Lewis y u, cc phn t trung ha ho c cc phn t dung mi (s dung mi gi i) Phn c c, c proton (r u, n c,)

SN2
Methyl > 1r > 2r BaseLewis m nh, n ng cao

Phn c c, khng c proton (DMF, DMSO,) Nhm xu t: nh h ng nh nhau trong c hai lo i ph n ng: nhm xu t cng t t khi n c tnh base cng y u.

Dung mi

SN1 OR SN2 ???

S n ph m c a (a) l ng phn c a s n ph m (b). Ph n ng SN1 Hay SN2 ?

S p x p cc

ng phn c

cng CTPT C4H9Cl theo chi u gi m d n ho t tnh trong ph n ng v i sodium iodide trong acetone?

Ha h c l p th c a A v B?

Ha h c l p th c a 2-Bromobutane?

V n t c ph n ng t ng khi dng m tl ng nh NaI lm xc tc. Gi i thch?

PH N NG TCH (KH ) (ELIMINATION REACTION)

elimination C C Y Z (YZ) C C

 Phn t b lo i: HX ( ehy rohalo en

ha), n c ( ehy rat ha),  Quy t c Zaitsev: s n ph m chnh t o thnh s l alkene man nhi u nhm th nh t

b n c a Alkene

PH N

NG TCH

PH N
Br CH3CH2CHCH3 2-Bromobutane Br CH3CH2CCH3 CH3 CH3CH2O Na+ CH3CH2OH CH3CH2O Na+ CH3CH2OH

NG TCH
CH3CH !CHCH3 2-Butene (81%) + CH3CH2CH CH2

1-Butene (19%) CH3

CH3CH !C(CH3)2

CH3CH2C

CH2

2-Bromo-2-methylbutane

2-Methyl-2-butene (70%)

2-Methyl-1-butene (30%)

Hai c ch : Tch E1 v Tch E2

PH N

NG TCH E2

C n s d ng Base m nh v n ng base cao.

Y UT

L P TH TRONG E2

Nguyn t H, hai nguyn t C v nhm xu t X: anti periplanar

B
H

...

Anti periplanar

Anti transition state

:
X

Alkene

Y UT

L P TH TRONG E2

Y UT

L P TH TRONG E2

Y UT
H H H3C H
H

L P TH TRONG E2
tBuOK
t BuOH

CH3CH2CH2Br +

CH3CH=CH2
Br

H Br Br H H CH3
H

H H

H CH3 H
Br

H3C
H

H
Br

H
Br

H
H

H
H

CH3 H
H

CH3

Y UT
B: H C Br H Br Br H h h h Br H C h

L P TH TRONG E2
H KOH Ethanol Br C h h h C h

H Br

meso-1,2-Dibromo-1,2-diphenylethane

(E)-1-Bromo-1,2-diphenylethylene

Y UT

L P TH TRONG E2 v tr

Cyclohexyl halide: H v X u axial v l trans i v i nhau

PH N

NG TCH E1

Khng c n dng base m nh

PH N

NG TCH E1

Ch x y ra i v i nh ng ch t c th ion ha t o thnh carbocation b n v ng:  Alkyl halide b c 3  Benzyl halide  Allyl halide,

Ph n ng Th hay Kh ?

 Ch ng ng i l p th  Tnh base  Nhi t

CH

NG NG I L P TH

E2 hay SN2 ???

E2 hay SN2 ???

TNH BASE

TNH BASE

Nhi t

Ph n ng tch: S > 0

G < 0 khi T cng l n Ph n ng tch c n nhi t

Nhm xu t trong E2 v E1

Nhm xu t trong E2 v E1

S t o thnh Tosylate
Reagents: ROH + TsCl + Pyridine

S t o thnh Mesylate
Reagents: ROH + MsCl + Triethylamine

S n Ph m Chnh?

S n Ph m Chnh?

S n Ph m Chnh?

S n Ph m Chnh?

C ch ?

C ch ?