CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

M u

Isidor Isaac Rabi (Nobel 1944)

1938: Proton v notron trong ht nhn nh mt nam chm.
V th, trong t trng ngoi, cc momen t ca nguyn t
hoc phn t to nn mt trng thi cn bng . Khi a chm
tia cc phn t qua mt t trng ca mt sng v tuyn, th
hng ca mt s momen t b thay i. Khi chng chuyn
v trng thi ban u th pht ra bc x in t c tn s c
trng cho nguyn t hoc phn t

1
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

1946: Edward Mills Purcell (Harvard) v Felix Bloch (Stanford) (Nobel 1952): Pht trin
phng php o chnh xc t ht nhn v cc ng dng ca chng.

2
 K. Wthrich (Nobel 2002): xc nh cu trc 3 chiu ca i phn t

3
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

P.C. Lauterbur v P. Mansfield (Nobel 2003): Khm ph lin quan n hinh anh cng
hng t (MRI) nh o m co hinh anh cc b phn bn trong c th sng

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

5
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

6
7
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

NMR (nuclear magnetic resonance) l k thut c gi tr nht xc nh cu trc cc

hp cht hu c. Phng php NMR c hn ch l ch p dng cho cc ht nhn nguyn
t vi s hiu nguyn t (s th t Z) l hoc s khi (A) l v cc nguyn t loi ny c
spin ht nhn th mi c tnh cht t nh 1H, 13C, 15N, 19F, 31P
Cc ht nhn khng c tnh t nh 2D, 12C, 16O, 32S khng th hin trn ph NMR

xc nh cu trc ca HCHC, phng php ph thng dng nht l 1H v 13C sau

o ty theo loi hp cht m c th s dng thm ph 15N, 19F, 31P

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.1. C s l thuyt ca phng php ph NMR

3.1. 1. Tnh cht t ca ht nhn

Nguyn t c cu to t ht nhn v lp v electron. Ht nhn nguyn t vi s

th t Z, s khi A c Z proton v A-Z ntron

Ht nhn nguyn t lun quay quanh trc ring ca n nn sinh ra momen ng

lng gi l momen spin ht nhn, k hiu P .
Ht nhn mang in tch dng quay quanh trc quay lm xut hin mt t trng
nh mt nam chm vnh cu

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Tnh t ca ht nhn nguyn t c biu th nh lng qua momen lng cc t

-momen t c gi tr tuyt i l .
P -momen ng lng (momen spin) hay spin ht nhn c gi tr tuyt i l p.
-hng s t l gyromagnetic (hng s t l t hi chuyn)

10
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.1.2. Tnh cht ca ht nhn c tnh t trong t trng ngoi

Ht nhn t khi khng c t trng ngoi

Ht nhn t trong t trng ngoi Ho: khuynh hng sp xp momen t ca ht

nhn cng hng ng sc vi t trng ngoi

Ho

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Mt ht nhn t c momen t nh hng di mt gc so vi hng t trng

ngoi khng i H 0 . T trng ny lm cho nam
chm chuyn ng tu sai (chuyn ng vng)
quanh trc t trng ngoi.

Tc gc ca chuyn ng tu sai (raian trn giy):

= 2
vi tn s gc s vng quay trong thi gian mt giy
khng ph thuc vo gc nghing v t l thun vi
cng t trng ngoi H0 :
H0 (3.4)
H s t l l hng s gyromagnetic

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Xt anh hng ca t trng ngoi c gi tr khng ln H1

vung gc vi H0. H1 c khuynh hng lm lch nam chm
vo mt phng xy nhng tc ng ny c hiu lc rt nh
khi H1 quay quanh trc H0 vi tc gc (hay tn s gc)
khc vi tn s gc ca chuyn ng tu sai ca nam chm
quanh trc t trng ngoi H0. Nu thay i rt chm s
quay ca H1 qua gi tr tn s gc chuyn ng tu sai ca
nam chm quanh trc H0 th khi t c gi tr tn s ny,
gc s thay i rt mnh tng ng vi s trao i nng
lng gia ht nhn t chuyn ng tu sai quanh trc t
trng H0 vi t trng quay H1.

Hin tng ny khng khc g dng cng hng, do o c khi nim cng hng t ht
nhn (NMR).
13
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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

S trao i nng lng trn tng ng vi s hp th hoc pht ra bc x v c th

ghi nhn bng thit b thc nghim ghi o cc tn hiu NMR gi l phng php NMR:

Ht nhn t cn c t trong t trng khng i H0, sau tc ng ln ht nhn

bc x in t H1 (sng raio) sao cho t trng H1 ca bc x ny quay quanh trc H0

vi tn s gc c gi tr cn thit gy nn s cng hng.

Khi ht nhn quay quanh trc c momen ng lng ht nhn (momen spin) P
C ln:
h
P I ( I 1)
2 h-hng s planck
Gi tr tuyt i ca momen t I-s lng t spin ht nhn
h
P I ( I 1)
2
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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Hnh chiu ca cc momen ng lng v momen t ln trc Z nhn nhng gi tr

gin on
h h
Pz m z Pz m
2 2

Vi m-s lng t t nhn cc gi tr I, I-1, I-2,.0, n -I, ngha l c (2I+1) kha nng
nh hng khc nhau

VD: Xt trng hp cc ht nhn t c I = (1H, 13C, 19F, 31P)

Khi o gi tr c th ca s lng t t m ch l +1/2 v -1/2
v gi tr:
1 h 1 h 3 h
Pz Pz P
2 2 2 2 2 2
1 h
cos z 2 2
P 1 1
Kha nng th hai cos
P 3 h 3 3
2 2 17
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.1.3. Tn s cng hng

Th nng E ca ht nhn t nh hng di gc so vi ng sc ca t trng ngoi

H0 c xc nh theo phng trnh

E H0 E H 0 cos

Do o nu t ht nhn t I = 1/2 vo t
trng H0 th nng lng ca n s hoc
1
tng hoc giam mt i lng H 0
3
ph thuc vo s nh hng c php
ca spin hay ht nhn t 2
E h H 0
1 3
E 2 H 0
Do: 3
h h 3 H 0
P I ( I 1) nn Vy
2 4 2
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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

nh lut phn b Boltzmann: k = 1,38.10-23 J.K-1

Vi 1H: Ho = 9.4 T, E = 2,65. 10-25 J, T = 300K th:

Ht nhn 19F 13C 31P 1H

(rad.T1.s1) 2,518.108 0,6728.108 1,084.108 2,67.108

(H ) H 0
= 4,00195. 108 Hz hay khoang 400 MHz
H 0 2
Do
2 (C ) H 0
= 1,00685. 108 Hz hay khoang 100 MHz
2 19
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Nguyn ly hoat ng ca may NMR

20
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

21
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.1.4. Qua trinh hi phc spin

a) Vect t tnh M0
Vect t tnh Mo c nh ngha bng tng cc
vect t ca cc ht nhn trong mt n v th tch

Do s ht nhn trng thi ln hn TT nn vect

M0 cung hng vi t trng ngoi H0

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

b) Qua trinh hi phuc spin

Cn bng nhit c xc nh thi cc ht nhn t nm cn bng vi nhau hai trng thi
va theo phn b Boltzmann.
Khi p mt song ngang radio (RF) thi cn bng b pha v chuyn n mt trng thi
CB mi. S quay tr li TT CB nhit ban u gi l qu trinh hi phc spin. Nh vy
thi gian phc hi l thi gian sng ca trng thi kch thch.

Phn bit: hi phc spin dc (T1) va hi phc spin ngang (T2)

Hi phc doc: S quay tr li gia tr t tnh cn bng M 0theo trc z. Thi gian tng
ng gi l T1 va c gi l hi phc spin mng li. S hi phc ny lin quan ti s
trao i nng lng (entanpi trao i) do mt s ht nhn t chuyn trng thi (t thp
n cao hoc ngc li)

25
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Ti thi im cn bng, vc t t tnh theo trc z trng vi hng ca t trng ngoi Bo,
thnh phn t tnh theo phng xOy bng 0

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Thi gian T1 xc nh ty l xung lp li c m ta bng phng trinh di y. i

vi proton, gia tr T1 vo khoang t 0,5 n vi giy

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Hi phc ngang: Sau khi mt trng thi CB, cc thnh phn t theo phng ngang s
tng, tng n cc i va sau o giam dn v trit tiu tng ng vi khoang thi gian
T2. iu ny l do tng tc gia cc spin ht nhn dn n mt s gn kt gia cc
momen t do co s thay i tc ng t trng ngoi. Hin tng ny con gi l hi
phc spin-spin. Qu trinh ny khng lm thay i NL, hi phc spin-spin n thun
ch l qu trinh entropi (Khng xay ra qu trnh chuyn trng thi ca cc ht nhn t)

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Uncorrelated

Correlated

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

T2<T1: T2 xc nh rng ( phn giai) ca tn hiu, T2 cng nho thi tn hiu co

phn giai cng kem

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Phng trinh Lorentz

rng na pic

Ti = 1/2 co f(v) = K/2 nn

Vy = 1/T2

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.2. chuyn dich hoa hoc

3.2.1. Hng s chn v t trng hiu dng

Khi t mt ht nhn nguyn t vo mt t

trng ngoi H0 th lp v electron quay
quanh ht nhn s sinh ra mt lng cc t c
t trng ngc hng vi t trng bn
ngoi v cng ca t trng o t l vi
cng t trng ngoi.

iu ny c ngha l electron che chn mt phn ht nhn khi t trng ngoi.

T trng tc dng ln ht nhn ch cn l:
H c H 0 (1 )
Trong o: Hc-t trng hiu dng
- hng s chn 32
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

ln ca c th tnh theo cng thc Lamb

4 e2
2
r. p(r )dr
3mc

Trong o: e-in tch electron

m-khi lng electron
c- vn tc nh sng
P(r)- mt electron bao quanh ht nhn
r- khoang cch t tm ht nhn n electron

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Nguyn nhn xut hin hng s chn

a) Hiu ng nghch t (diamagnetic)

Khi t mt ht nhn t vo trong mt t

trng ng nht H0, lp vo electron quanh ht
H
nhn cung quay sinh ra mt momen t H ngc
hng vi t trng H0 va lm t trng ny yu
i. Hiu ng chn ny gi l hiu ng nghch t.
Hng s chn phu thuc vo m my bao
quanh ht nhn. Nu lp e cng dy thi hng s H0

chn cng ln va ngc li.

Do o, nu nguyn t hoc nhom th bn cnh ht e thi lm giam mt e bao

quanh ht nhn khi o hng s chn nho, chuyn dch ln va ngc li

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

VD:

Nhom th X m in ca X (CH3)

F 4,0 4,22

Cl 3,5 3,01

Br 3,2 2,65

I 3,0 2,15

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

b) Hiu ng thun t (anisotrop)

Khi t phn t cha ht nhn t vo t H

trng ng nht mnh, t trng ny s gy ra

dong in cam ng kn trong phn t, cng H

ca dong ny phu thuc vo linh ng ca cc H H

in t xung quanh phn t. Dong in kn ny H0
s gy ra mt t trng phu.
T trng phu ny s chia khng gian thnh
hai phn cho tn hiu khc nhau.

Phn pha trong, t trng phu ngc hng vi t trng ngoi nn t trng hiu
dng He < H0. pha bn ngoi, t trng phu cung hng vi H0 nn He > H0. Do o
cc proton nm khoang khng gian bn ngoi s co hng s chn nho hn. Hin tng
ny gi l hiu ng thun t
36
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Hiu ng anisotrop th hin mnh benzen va cc hp cht thm khc. Proton trong
nhom ch andehit cung hon ton tng t. Trong cc trng hp ny, hng s chn nho
nn co chuyn dch hoa hc ln.
H ca nhn thm: 7-8 ppm H H
H H
H ca andehit: 9-10 ppm
H H H
H H
Hiu ng anisotrop cung th hin rt ro i vi H H
H H H
h vong ln co tnh thm nh 18-annulen. H vong
H H
ny cho hai tn hiu khc nhau ca proton: cc H H
proton ngoi vong co H = 9,17 ppm, con cc Annulen
proton trong vong co H = - 2,96 ppm

Ngc li, axetilen thi H co chuyn dch hoa hc nho hn vi no nm pha

trong nn b chn nhiu hn H = 2-3 ppm

37
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.2.2. chuyn dch ha hoc

Trong thc t khng th tim c mi trng m ht nhn khng co electron, do o ngi

ta s dng mt cht chun xc nh s cng hng ca cc proton khc nhau.
Tetramethylsilan (TMS) c la chn vi mt s tnh cht c trng sau y:

+ Tt ca cc proton trong hp cht l tng ng nhau

+ Cc proton ny b chn rt mnh vi m in ca Si nho hn nhiu so vi C do o

cc proton trong hu ht cc HCHC co hng s chn nho hn: (TMS) > (R)
+ TMS l cht d bay hi nn d dng loi bo ra khi hn hp HCHC (Ts = 26oC)

41
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

dich chuyn hoa hc (tn s) ca cc proton so vi cht chun TMS l:

Trong ky thut o ngi ta khng th xc nh c gia tr tuyt i ca hng s chn

va nhng co th xc nh gia tr tng i so vi cht chun TMS

Thc nghim cho thy proton ca hu ht cc hp cht hu c c chuyn dch ha

hc rt nho t 0 n 10.10-6 hay t 0 n 10ppm. chuyn dch ha hc khng c
th nguyn, biu din vo phn triu ppm (parts per million).
Quy c : TMS = 0 42
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

chuyn dch ha hc ngoi thang hay dng, ngi ta cn dng thang vi cht
chun TMS c chuyn dch ha hc quy c = 10 ppm 10 ppm

Cac yu t anh hng n dch chuyn ha hoc

Lp vo electron cng ln thi hng s chn cng ln va ngc li. Khi lp vo electron tng
thi in t trng hiu dng giam do o chuyn dch hoa hc cng nho nh minh ha
theo hinh sau:

43
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

chuyn dich hoa hc s tng khi m in ca nguyn t lin kt vi proton tng

VD:
Hp cht CH3I CH3Br CH3Cl CH3F
(ppm) 2,3 2,7 3,4 4,5

Ngoi ra, dch chuyn hoa hc con phu thuc vo tnh bt ng hng ca s nhy
t ca phn t do electron trong vong nh:
Proton lin kt trc tip vi nhn thm (khng b chn)
Proton trong nhom andehyt (khng b chn)
Proton trong nhom axyle (b chn)

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

chuyn dch ha hc ca proton trong ph 1H-NMR

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.3. ng cong tich phn

Mt thit b cho phep o din tch ca cc pic. Din tch ny ty l thun vi s proton
tng ng trong cc pic. Tuy nhin vic tnh ton din tch thng kho khn do xut
hin a vch trn mi pic. khc phc ngi ta s dng ky thut tch phn tn hiu
ve mt ng cong bc thang trn ph gi l ng cong tch phn. Chiu cao ca cc
bc khng cho bit chnh xc s proton nhng cho bit ty l s proton ca cc nhom
tng ng

ng cong tch phn (integration) co y ngha quan trng trong phn tch NMR
Xc nh ty l s proton trong mi pic trn ph
Phn tch nh lng cc hp cht trong hn hp vi chiu cao ca bc thang ty
l vi nng cc cht trong hn hp: ty l nng , hiu sut phan ng,
chuyn hoa
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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.4. Tng tac spin-spin

Trong ph NMR, mi tn hiu co th bao gm nhiu pic nho. Hin tng ny l do

tng tc gia cc ht nhn gi l tng tc v hng (couplage scalaire)
Phn bit hai loi tng tc:
Gia hai loi ht nhn khc nhau (heteronucleaire):
VD nh gia 1H va 13C, c ky hiu l 1J:

Gia hai ht nhn cung loi (homonucleaire): vd nh

tng tc gia cc proton, c ky hiu l nJ vi n>1

Tng tac S lin kt Tn goi

2J 2 geminal
3J 3 vicinal
4J 4 Khoang cch xa

52
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.4.1. Tng tac gia hai proton

Xet tng tc gia hai proton A-X. Trong s cng hng t ca proton A, do anh hng
ca tng tc t ht nhn t X tuy thi im m co th lm tng hoc lm giam t
trng hiu dng i vi t trng bn ngoi do o tn hiu ca proton A b tch thnh 2
pic. Khoang cch gia hai pic gi l hng s tng tac (constante de couplage) c
biu thi bng Hz (Hertz)

Tng tc gia hai ht nhn c c trng bng hng s tng tc J no ch phu thuc
vo ban cht ca cc ht nhn m khng phu thuc vo mnh, yu ca t trng bn
ngoi Ho

Qu trinh cung xay ra hon ton tng t i vi proton X

JAX = JXA
53
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.4.1.1. Ph bc 1

Nu hai ht nhn A va X co tng tc spin vi nhau va A-X > 6 JAX thi ph NMR
gi l ph bc 1. Khi o ngi ta biu din h ht nhn bng cc ch ci cch xa nhau
nh AX, AMX, A2X

J AX J AX
> J H AX

A B

56
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Mi proton cho mt tn hiu trn ph, tuy nhin cc ht nhn tng ng nhau xut
hin cung mt v tr vi chng co cung dch chuyn hoa hc.

VD

57
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Chu y
Cc proton bn cnh trung tm bt i khng tng ng nhau (protons diastereotopics)

Do bn cnh trung tm bt i nn bt c cu dng no hai proton Ha va Hb u khng

tng ng nhau

62
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Trong ph 1H NMR , mi proton cho mt tn hiu doublet (d)

OH
Br
CH3

6 5 4 3 2 1 0
PPM
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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Tn hiu ph ca cc ht nhn t khng nhng phu thuc vo v tr, ban cht ca cc ht

nhn m con phu thuc vo dung mi, nhit

64
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Anh hng ca nhit

Hai ph di y l ca CH3OH hai nhit khc nhau l -65oC va 40oC. Hin tng ny
xay ra l do qu trinh trao i proton linh ng trong cc nhom chc trong ru, amin, axit
cacboxylic nhit thp qu trinh trao i xay ra chm hn so vi tn s quet ca my
nn chng ta vn quan sat c hin tng tng tc spin. nhit cao qu trinh trao i
xay ra nhanh nn khng con tng tc spin-spin.

66
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Cac dang pic trong ph 1H-NMR

a) Dang AMX

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

b) Dang AX2

Hai proton tng ng tng tc vi proton A vi cung hng s tng tc

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

c) Dang AX3

Proton A tng tc vi 3 proton tng ng X

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Tng t i vi dng AXn, tn hiu ph ca A gm cc pic m chiu cao ca no tun theo

quy tc tam gic Pascal

singlet (s) 1

doublet (d) 1 1

triplet (t) 1 2 1

quartet (q) 1 3 3 1

quintet (quin) 1 4 6 4 1

sixtet (six) 1 5 10 10 5 1

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CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Hinh dng pic ca proton A trong ph 1H-NMR

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 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)
3.4.4.4. Cc dang tng tc spin-spin trong ph 1H-NMR
a) Tng tac geminal
o l tng tc gia hai proton khng tng ng lin kt vi cung 1 nguyn t cc
bon. Hng s tng tc l m con ln ca no chu anh hng mnh bi goc lin kt
gia chng

75
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

V d: Do nhom tBu co th tch ln nn phn t khng th to cn bng gia cc cu dng

gh hoc thuyn, con trng hp th 2 dng bicyclo phn t cng nhc

Dng tng tc geminal cung thng gp trong trng hp trong phn t co nhom -
CH2- bn cnh mt trung tm bt i
Ha Hb
R1
R
R3 R 2
76
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

b) Tng tac vicinal

o l tng tc gia hai proton qua 3 lin kt, hng s tng tc c ky hiu l 3J

77
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

78
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

79
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

ng cong Karplus
Hng s tng tc 3JHH gia hai proton vicinal phu thuc vo goc nhi din gia cc lin
kt C-H
3J
HH = 0,3 0,5cos + 9,2cos2

80
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Trong cu hinh dng vong ca phn t

Protons HaxHax HaxHq HqHq

() 180 60 60
3J 11,8 3,9 3,9

81
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

c) Tng tac khoang cach xa

Tng tc gia hai proton cch xa t 4 lin kt tr ln. Dng ny thng quan st c
vi cu trc hinh M hoc W nh hinh v

Trong mt s trng hp, co th quan st c 9J cc phn t dng polien

82
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

83
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.4.4.5. Quan h gia cu truc va hng s tng tac

84
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

85
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

86
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

87
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Sec-butylic

88
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

89
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

90
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Hy cho bit cu to ca HCHC sau

91
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

92
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

93
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

94
95
96
97
98
C4H8O2

99
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)
3.4.4.6. Hin tng trao i proton
Cc proton lin kt trc tip vi cc nguyn t co m in ln nh O, N (ru, amin,
axt) co th nhanh chong trao i vi cc proton (hoc deuteron) trong dung dch nn cc
proton ny co th khng to tng tc vi cc proton bn cnh

Trong ph ca etanol tuyt i khan hinh dng ca ph nh sau

100
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Trong trng hp co ln nc, qu trinh trao i proton din ra do o khng con tng
tc spin gia H trong nhom OH vi cc proton bn cnh

101
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Chu y: Nu thm lng rt nh CF3COOH vo trong mu o thi tng tc spin ca

proton trong nhom chc cung mt i do axit TFA xc tc cho qu trinh trao i proton gia
cc phn t ru lm cho qu trinh xay ra nhanh hn

Do s trao i proton nn v tr tn hiu ca proton trong nhom chc OH rt linh

ng. V tr ca no co th thay i tuy theo nng , nhit thm ch l khng xut
hin trn ph. Qu trinh cung xay ra tng t trong amin, axit cacboxylic...

102
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

103
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.4.1.2. Ph bc cao

Tt ca cc loi ph khng th phn tch theo ph bc 1 gi l ph bc cao. Hu ht

cc ph ny co (A - B) JAB. Khi o ngi ta ky hiu cc ht nhn bng cc ch ci
lin tip nhau nh AB, A2B, ABC Vic phn tch ph ny rt phc tp, trong nhiu
trng hp khng th phn tch trc tip. Loi thng gp l h ph AB (AB system).
Hinh dng pic ca hai ht nhn ny to nn hinh chop nhn (hiu ng mi nha: roof
effect = effet de toit)

Hin tng ny hay gp trong cc hp cht cha ni i (ethylenic compound) hoc

trong nhn thm (aromatic compound) 104
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

105
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

106
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

107
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

108
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Cac phng phap h tr cho phn tich ph

i vi ph bc cao hoc l cc cht co cu trc phc tp thi vic phn tch ph gp nhiu
kho khn. giam bt cc kho khn ny thi ngi ta s dng mt s ky thut ring trong
qu trinh o. Sau y l mt s phng php thng dng:

Nng cao tn s may ghi

Phn tch cng n gian nu nh ty s /J cng ln (dng ph bc mt), tuy nhin J l
hng s khng phu thuc vo cng trng ngoi. Gia tr cng ln khi tn s my
o cng ln, khi o khoang cch cc pic cch xa nhau vic phn tch ph tr nn d dng
hn

Thay i dung mi
chuyn dch hoa hc ca mi proton phu thuc mnh vo dung mi khi ghi ph trong
khi hng s tng tc J khng thay i vi th khi chn c dung mi thch hp s gip
cho vic phn tch ph thun li va d dng hn
109
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Thay th cac ng vi (isotop)

Khi thay th proton bi tri s lm n gian hoa ph 1H-NMR bi tri khng phai l
ht nhn t nn chng khng co tng tc vi proton bn cnh iu o lm cho ph n
gian hn va vic phn tch ph tr nn d dng hn

110
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Cng hng t kep

ghi ph NMR ngi ta phai s dng mt t trng cao tn H1. Nu a vo mt t

truong cao tn khc H2 co cng t trng u ln lm thay i mc NL, tn s 2
ca no phu hp hon ton hay gn hon ton vi ng cng hng. Qua y ngi ta
co th xc nh c cc tn hiu thuc v proton no trong phn t. Hin tng ny
c gi l cng hng kep. Da vo cng t trng H2, ngi ta chia thnh hai
loi:

H2 mnh dn n trit tiu tng tc spin

H2 yu dn n spin-tickling

111
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

a) Trit tiu tng tac spin

Hin tng ny xay ra i vi h ph bc 1. Chng hn ta co h ph AXn, nu tc dng

mt t trng phu H2 vi tn s bng tn s ca trung tm a vch ca ht nhn A ri
quan st tn hiu nhom ht nhn X thi thy tn hiu ca nhom ny mt i mt vch n.
Nguyn nhn ca hin tng trn l do khi tc dng t trng phu mnh H2 lm mt i t
trng phu ca ht nhn A tc dng ln ht nhn X do o ch con H2 tc dng ln ht nhn
X no ch co mt hng iu chnh trong t trng ngoi va ta ch thu c mt tn hiu
trn ph, s tng tc spin a b trit tiu.

112
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

113
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

b) Spin-tickling
Khi tc dng mt t trng phu H2 co tn s phu hp vi tn s bc chuyn nng lng
no o ca h spin va u gy nhiu cho mc NL trn thi cc tn hiu ng vi cc bc
chuyn NL ca h hoc b phn tch ra hoc l thay i cng .

VD: Trong ph 1H-NMR ca 3-amino propan-2-enal trong hinh di y: a l ph co

tng tc spin, b l ph m proton X c bc xa va ph c l proton M c bc xa.
Ngi ta quan st c s thay i trn cc proton khng b bc xa. T o ngi ta co th
giai thch c dng pic ca A va tnh c hng s tng tc vi cc proton M va X

114
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

115
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

S dng tac nhn gy chuyn dich

i vi cc cht phc tp, nhiu khi cc tn hiu ph chp vo nhau khng phn giai
c. phn tch chng ngi ta s dng phng php to phc. Thm mt t mui ca
nguyn t t him vo trong mu o, no s to phc vi cht dn n tch c tn hiu
trn ph. Trong nhiu trng hp phng php ny co th phn bit c cc i i
quang (enantiomer). Cc cht ny c gi l tc nhn chuyn dch

VD: Cc cht to phc, cc mui phc cht ca Europi (Eu) lm chuyn dch tn hiu
cng hng v pha trng thp. No s to phc vi cc trung tm giu electron nh OH,
NH, CO, CN

116
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

2,2,2-trifluoro,1(9-anthranyl)-ethanol (TFAE)
117
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

1H NMR, 300 Hz, CDCl3

A B

Tin hiu cua nhom C-CH3 trong ph cua mexilentine vi s co mt cua cht tao phc B
(TFAE) va khng co cht tao phc (A)

118
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

119
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

VD: Xd CT

120
121
122
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

C8H7BrO

123
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

124
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

125
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

126
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.5. Ph 13C - NMR

3.4.1. ng v 13C v ph 13C-NMR

Do ng v 13C ch chim 1,1% lng ht nhn cacbon trong t nhin nn so vi ph 1H

thi phng php ph 13C kem nhay hn nhng thang dich chuyn hoa hc ln hn ln
nhiu. T nm 1970 cc tr ngi o c khc phc nh s dng cc k thut in t
tin tin v my tnh

ng dng in hinh ca phng php ph 13C l da vo dch chuyn hoa hc ca cc

pic ca cc nguyn t C. n gian, trong phng php o ph 13C cc tng tc gia
cc ht nhn C-C va C-H c loi bo. Mi pic trong ph cacbon la mt tn hiu nhn va
net ng vi mt nguyn t cacbon khng tng ng.

dch chuyn hoa hc ca cc nguyn t C nm trong khoang t 0 n 220 ppm

127
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Cng vch ph trong ph xoa tng tc spin 13C ty l vi:

S nguyn t hydro gn vi nguyn t cacbon
S nguyn t cacbon tng ng

Da vo cng cc vch ph co th suy on s b v tr cc nguyn t cacbon trong

phn t
3
2

3 CH3

4
C
1

(CH 3) 3C-OH 3 2
1
4 N C O
3 2
128
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

dich chuyn hoa hoc cua cac nhom chc trong ph 13C 129
C8H7BrO

130
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

3.6. Phng phap DEPT (Distortionless Enhancement by Polarization transfer)

Trong phng php ny, tn hiu ca nhom -CH, -CH3 nm pha trn, tn hiu ca nhom
CH2 quay xung pha di. Nguyn t C bc 4 khng cho tn hiu trn ph

131
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

132
133
134
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)
3.7. Phng phap ph 2D

C s ca phng php ph 2D-NMR l da trn nguyn tc ph CHTN bin i

Fourier do o con gi 2D-FT-NMR.
Theo phng php ny, t trng cao tn H1 khng tc dng lin tc ln h ht
nhn nguyn t t sn trong t trng khng i Ho. Ngi ta tc dng mt xung
vung H1 ln ht nhn t theo hng trc x vi di (90o)x. Xung u tin ny lm
cho momen t chuyn ng quanh trc z s quay theo hng trc y va hng song
song vi trc y. Sau xung ny momen t s tnh tin t do vi tc trn mt
phng xy. Ti thi im t1 momen t quet c mt goc = t1, giai on ny c
gi l giai on trin khai (preparation) . Tip theo tc dng mt xung (90o)x ln hai,
s lm quay momen t xung pha di theo mt phng xz. Xung ny tc dng ln
momen t theo thnh phn trn tc x va z tng ng l sint1 va cost1. Giai on
ny c gi l hoa trn (evolution).

135
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Cui cung tc ng thm mt xung (90o)x , lc o moment t s ri mt phng xz v

trc y. Cng ca tn hiu cng hng ty l vi cost1. Giai on ny gi l giai on
thu hi (detection) vi thi gian keo di t2 va xut hin tn hiu suy giam cam ng t do
(Free induction decay signal vit tt FID)

136
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

Ph cng hng t nhn 2 chiu l mt trong nhng phng php ng dng rt tt trong
phn tch cu trc nhm xc nh ro v tr cc pc tng ng ca cc ht nhn t. Phng
php ny co c im nh sau:
Biu din tn hiu ph trn ca hai chiu trong h ta vung goc
Th hin cc tng tc spin gia cc tn hiu

137
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

138
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

139
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

COSY (Correlation spectrocopy)

Ethyl benzen

140
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

141
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

142
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

143
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

144
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

145
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

146
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

HMQC (Heteronuclear multiple-quantum correlation spectroscopy)

HSQC (Heteronuclear single-quantum correlation spectroscopy)

147
CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

148
149
 CHNG 3: PHNG PHP PH CNG HNG T HT NHN (PH NMR)

HMBC (Heteronuclear multiple-bond correlation spectroscopy)

150