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H CH MINH
( KHOA HA )
HA HC LP TH
V TH THU HNG
TP. H CH MINH-2002
MC LC
Phn A: L thuyt
Chng 1: Khi nim c bn.......................................... 5
Chng 2: ng phn quang hc .................................. 17
Chng 3: ng phn hnh hc..................................... 38
Chng 4: ng phn cu trng ca hp cht khng vng
..................................................................... 50
Chng 5: Cu trng ca hp cht vng no .................. 62
Chng 6: Ha lp th ca d t v Polymer................. 92
Chng 7: Ha lp th ng......................................... 113
Phn B Bi tp
ng phn quang hc ................................. 128
ng phn hnh hc.................................... 132
ng phn cu trng................................... 135
Phn ng th SN ............................................................... 138
Phn ng tch ............................................. 141
Phn ng cng ............................................ 144
Ti liu tham kho.......................................................... 148
LI NI U
Ho hc lp th (Stereochemistry) l mt khoa hc
nghin cu v cu trc khng gian ca vt cht v nh
hng ca cu trc ny n tnh cht ca chng.
Ho hc lp th c in ch ch trng n cc ng phn
lp th trng thi tnh nh ng phn hnh hc, ng phn
quang hc. Nhng gn y do s pht trin ca hc thuyt
v cu trng (conformation) v phn gii cu trng
(confornational analysis); v s tng hp nh hng lp th
trong cc phn ng ho hc; v quy tc bo ton tnh i
xng ca cc orbital... Cng vi s xut hin cc phng
php vt l nh quang ph t ngoi, quang ph cng hng
t ht nhn, nhiu x tia X, nhiu x electron.... Cc nghin
cu v ha hc lp th cho ta nhiu hiu bit mi v s
ph thuc ca cc tnh cht v nhng c tnh tinh vi v s
phn b khng gian ca cc nguyn t trong phn t, trong
vic gii thch c ch phn ng v c bit ha lp th cn
gii thch c hot tnh sinh l khc nhau ca cc ng
phn lp th.
Ha hc lp th ng nghin cu nhng chuyn ha cht
khc nhau ca cc ng phn lp th gy nn bi cc c
im cu trc khng gian ca chng nh hin tng racemic
ha trong phn ng th SN1, SR, SE, s nghch chuyn cu
hnh trong phn ng th SN2, s lu tr cu hnh trong phn
th SNi, epimer ha trong phn ng cng AN vo hp cht
carbonyl....
Nhiu cng trnh nghin cu v ha hc lp th c
nh gi cao, mt s c trao gii Nobel v ha hc, phn
nh vai tr tm c ca mn hc ny.
Vi tnh cht quan trng ca ha hc lp th, mt lnh
vc khng th thiu c i vi ha hc hin i, nn s ra
i quyn sch ny hy vng gip cc sinh vin chuyn ha
b sung kin thc v h tr cho qu trnh hc tp v nghin
cu ca mnh.
Do kh nng cn nhiu hn ch nn chc chn khng th
trnh nhng thiu st. Rt mong nhn c cc kin ng
gp chn thnh ca qu ng nghip v bn c sch
c hon chnh hn trong nhng ln ti bn sau.
Tc gi
PHN A
L THUYT
Chng 1:KHI NIM C BN
V HA HC LP TH
1. 1
1.1. Phm vi nghin cu ca ha hc lp th
1.2. Lc s
1.2.1. c tnh ca hp cht trin quang
1.2.2. Thuyt carbon t din
1.2.3. ng phn hnh hc
1.2.4. ng phn quang hc
1.2.5. ng phn cu trng (ng phn quay)
1.3. Cch biu din nguyn t carbon t din.
1.3.1. Cng thc chiu hp cht c mt nguyn t C
1.3.2. Cng thc chiu hp cht c hai nguyn t C
1.3.2.1. Cng thc tam th nguyn
1.3.2.2. Cng thc phi cnh
1.3.2.3. Cng thc Newman
1.3.2.4. Cng thc Fischer
1.4. Cu hnh tng i v cu hnh tuyt i
1.5. Danh php cu hnh
1.5.1. Danh php D,L
1.5.2. Danh php R,S
1.5.3. Danh php E,Z
1.1. PHM VI NGHIN CU CA HA HC LP TH
Cng thc phng khng th m t y cc dng ca phn
t. S kho st v cc kha cnh kin trc ca phn t trong khng
gian tam th nguyn rt cn thit. l phm vi nghin cu ca
Ha lp th.
Mun hiu r hot tnh ca mt hp cht hu c, trc ht
ngi ta phi bit cch cu to ca n v k l xc nh cu
hnh ca phn t.
Cu to ca phn t l trt t sp xp cc ni cc
nguyn t trong phn t.
Cu hnh ca phn t l cch sp xp trong khng gian
ca nhng nguyn t (hay nhm nguyn t) quanh tm carbon i
xng.
Cu trng u i ca hp cht xc nh bi nh hng
cc nguyn t hoc cc nhm nguyn t gn nhau (tng tc
khng ni).
Kt qu ca ni cng ha tr nh hng l s to
thnh ng phn lp th gm c ng phn hnh hc v ng
phn quang hc.
Ha hc lp th c in ch ch trng n cc phn t
trng thi tnh lin h n cc ng phn lp th. Hin nay,
ha hc lp th tr thnh mt trong nhng ti quan
trng nht trong ha hc hu c l thuyt. Ha hc lp th
ng kho st s tng quan khng gian gia cc nguyn t
v cc nhm nguyn t chu phn ng, cng nh hng ca
s sp xp trn cn bng ha hc v vn tc phn ng.
1.2. LC S
1.2.1. c tnh ca hp cht trin quang
Nm 1811, Arago pht hin u tin kh nng quay mt
phng nh sng phn cc gi l tnh quang hot. Nm 1813, Biot
tm thy kh nng quay mt phng nh sng phn cc tinh th
thch anh. Nm 1815, Biot tm thy s quay tng t xy ra vi
mt s cht lng thin nhin: tinh du thng v dung dch ca mt
s cht rn (nh camphor). S khc bit quan trng gia hai d
kin thc nghim va k c Biot gii thch nh sau:
- Kh nng quay mt phng ca nh sng phn cc ca
thch anh lin quan vi c cu c bit ca tinh th (v n mt hn
khi tinh th c nu chy).
- Cn tnh quang hot ca hp cht hu c phi c lin
kt vi tnh cht ca nhiu phn t ring bit (v hin tng ny
c quan st trng thi lng v trng thi kh cng nh
trng thi dung dch).
Nm 1821, Herschel chng minh rng mt dng ca tinh th
thch anh lm quay mt phng ca nh sng phn cc theo chiu
quay kim ng h, cn dng i quang (ng vi nh ca dng u
trong gng phng) quay mt phng phn cc theo chiu ngc
li. Nh vy nng sut quang hot lin quan mt thit vi tnh bt
i xng ca tinh th.
Sau nhiu nm (1848 1853) kho st tnh quang hot ca hai
acid trch t cn ru nho, Pasteur xc nhn s hin hu ca hai
acid tartric: mt acid hu trin: quay mt phng ca nh sng
phn cc v bn phi (acid (+) tartric) v mt acid khng quang
hot (tiu trin): khng quay mt phng ca nh sng phn cc
(acid () tartric). Ngoi ra, Pasteur thnh cng trong vic tch
hai acid tiu trin thnh acid (+): hu trin v acid (-): t trin
(quay mt phng ca nh sng phn cc v bn tri). Hai acid ny
gi l hai ng phn i quang (hai ng phn i hnh). Theo
Pasteur, tnh quang hot khng phi do tnh bt i xng ca tinh
th m tht ra lin quan vi tnh bt i xng ca chnh cc phn
t acid tartric quang hot. Sau , Pasteur cn tm thy mt acid
tiu trin khc gi l acid meso-tartric. y l mt acid i xng
nn khng quay mt phng ca nh sng phn cc.
COOH COOH
H OH HO H
CH3 CH3
Acid (+) lactic Acid () lactic
Nu mt nguyn t carbon ni vi hai (hay nhiu hn) nguyn
t hoc nhm nguyn t th vt v nh s chng ln nhau c v
tnh quang hot mt hn.
Nm 1913, Bragg chng minh c s phn b t din ca
nguyn t Carbon bi nhiu x tia X ca kim cng. Nhng
phng php vt l khc nh nhiu x in t v ph nghim
cng xc nhn ngh ca Vant Hoff.
1.2.3. ng phn hnh hc
T nm 1875, Vant Hoff ngh biu din ni i trong
etylen th abC=Cab bng m hnh hai t din chung nhau mt
cnh nh sau: a a b
a
b b b a
cis th bn nhmtrans
Xt v mt hnh hc th nm trn mt mt
phng. Do , s quay quanh ni i l khng cn na v s phn
b ca nhm th ging nhau c th cng pha hoc khc pha
ca mt phng cha ni i.
a a a b
b b b a
cis trans
(a b)
Nm 1838, Liebig xc nh c s tn ti ca hai acid:
maleic v fumaric l ng phn ca nhau.
H H H COOH
H H H H
H H
1.3.2. Biu din phn t cha hai nguyn t C
- Cng thc tam th nguyn ca Etan
H
H
H
H
H
- Cng thc phi H
cnh: nhn theo trc C C
H H
H
H
H H
- Cng thc chiu Newman: trc C C vung gc
vi mt phng chiu, nguyn t C gn nht c biu din bng
vng trn, cc lin kt vi C ny xut pht t tm vng trn.
H
H H
H H
- H
Cng thc chiu Fischer: mch chnh ca phn t
hng theo chiu thng ng, cc lin kt hai bn l nhng lin
kt hng v pha trn mt phng, cc lin kt u trn v u
di l nhng lin kt hng v pha di mt phng.
H H
H H H H
H H H H
H H
1.4. CU HNH TUYT I V CU HNH TNG I
- Cu hnh tuyt i: l cu hnh thc s ca phn t
trong khng gian. Danh t hu trin (quay phi) v t trin (quay
tri) cho bit chiu quay ca mt phng nh sng phn cc b tc
ng bi cht hu c. y l kt qu c t thc nghim, ngi ta
khng th tin on dng no trong hai dng i quang ng vi
dng t trin hay hu trin.
- Cu hnh tng i: Trc nm 1951, ngi ta
khng c phng php no xc nh cu hnh dng hu trin
hay t trin ca hai dng i quang. Tuy nhin, ngi ta c th
xc nh cu hnh ca cc cht quang hot i vi nhau v i vi
hp cht mu c cu hnh bit. Cu hnh ny gi l cu hnh
tng i.
1.5. DANH PHP CU HNH
1.1.1. Danh php D,L
Hp cht c chn lm mu l gliceraldehid:
- Cu hnh ca dng hu trin c Fischer qui nh l
D (+) gliceraldehid.
- Cu hnh ca dng t trin c gi l L (-)
gliceraldehid.
CHO CHO
H OH HO H
CH 2OH CH 2OH
D-(+)-gliceraldehid L-(-)-gliceraldehid
K hiu: D, L l cu hnh tuyt i
Du (+) hay (-) lin h n chiu quay
a a
d
c d c
b
Cu hnh R Cu hnh bS
b d
Xt theo qui tc th t u tin: a>b; c>d
- E khi a, c v tr trans i vi nhau
- Z khi a, c v tr cis i vi nhau
Qui tc th t u tin
1. Cc nhm u tin c sp xp theo th t gim dn s
in tch ht nhn nguyn t ca nguyn t lin kt trc tip vi
C*
Th d -I > -Br > -Cl > -F
-SO3H > -OH > -NH2 > -CH3
2. Nu hai nguyn t gn trn C* ging nhau th xt
nguyn t lin kt trc tip vi nguyn t . Nu vn khng
chn c u tin th xt tip nguyn t th ba
Th d: -CR3 > -CHR2 > -CH2R > -CH3
-NR2 > -NHR > -NH2
3. Mt nguyn t lin kt i hay ba tng ng vi hai
ni n hoc ba ni n vi nguyn t (ch c mt lin kt
tht, lin kt cn li gi nh c u tin thp hn).
Th d: -CH=CH- tng ng vi CH
C
-CHO tng ng vi O
C O
N
-C(N tng ng vi H
C N
T > D > H
5. Cu hnh cis u tin hn trans; R u tin hn S
Th d: COOH CH OH 2
H OH H3C OH
CH3 CH2Br
(R) (S)
H CH 2-CH 3 F CH 2B r
H 3C CH 3 H 3C CH 2O H
(E) (Z)
COOH COOH
H 3NH
2
H 2N CH 3 (R)
CH H
COOH H
H OH HO COOH (R)
(S)
H OH HO COOH
COOH H
Chng 2: NG PHN QUANG HC
2. 1
2.1. nh sng phn cc v tnh cht ca n
2.2. Nhng cht quang hot
2.3. Phn cc k
2.4. Hp cht quang hot c hai hay nhiu Carbon bt i khc
nhau
2.5. Hp cht quang hot c hai hay nhiu Carbon bt i ging
nhau
2.6. Hp cht quang hot khng c Carbon bt i
2.6.1. Tnh bt i xng ca phn t
Trung tm khng trng vt nh
Tnh quang hot do c trc khng trng vt nh
Tnh quang hot do c mt phng khng trng vt nh
2.6.2. Tnh c th lp th ca cc qu trnh ha sinh
2.7. Bin th RACEMIC (dng tiu trin)
2.7.1. Bn cht ca bin th Racemic
2.7.2. S to thnh bin th Racemic
2.7.2.1. Phng php trn ln
2.7.2.2. Phng php tng hp
2.7.2.3. Phng php Racemic ha
2.7.3. Tnh cht ca bin th Racemic
2.7.3.1. Hn hp Racemic
2.7.3.2. Hp cht Racemic
2.7.3.3. Dung dch Racemic rn
2.7.4. S tch ring bin th Racemic thnh cc i quang
2.7.4.1. Phng php nht ring v kt tinh t pht
2.7.4.2. Phng php ha hc
2.7.4.3. Phng php to phc phn t
2.7.4.4. Phng php sc k
2.1. NH SNG PHN CC V TNH CHT
Theo thuyt in t ca nh sng th nh sng t nhin (nh
sng thng) gm nhiu sng in t, c vect in hng theo
tt c cc hng trong khng gian v vung gc vi phng
truyn sng.
(4
(2)
(3)
(1)
t
[M] = [] . M
t
100
M : phn t gam ca cht quang hot
2.4. HP CHT QUANG HOT C HAI HAY NHIU
CARBON BT I KHC NHAU
Rt nhiu hp cht t nhin nh: glucid, protid, steroid,
ancaloid trong phn t c nhiu nguyn t C*, cho nn vic
nghin cu v mt ha hc lp th nhng hp cht loi ny l rt
quan trng.
Hp cht c n nguyn t C* bt i khc nhau th c:
N = 2n ng phn quang hc
Th d 1: n = 1 OH
Acid lactic H C CH COOH c hai ng phn
quang hc lp thnh mt cp i quang :
3
COOH COOH
H OH HO H
CH3 CH3
Th d 2: n = 2 cAcid
bn(R)
ng phn quang hc Lactic
Lactic Acid (S)
Glucid tetroz CH 2 OH
*
CHOH
*
CHOH CHO
So ong phan
Dng quang hot Dng meso
So nguyen t C*
Th d: Acid tartric
*
* CH COOH
HOOC CH
OH OH
n = 2 c hai dng quang hot v mt dng Meso
COOH COOH COOH
H OH H OH HO H
H OH HO H H OH
COOH COOH COOH
Acid Meso-tartric Acid () tatric
* Hn hp ng phn t acid (+) tartric v acid (-) tartric l mt
dng khng quang hot (bin th racemic; hn hp tiu trin) l
do b tr ca hai phn t i quang.
* ng phn acid meso-tartric khng quang hot do s b tr
ni phn t, khng th dng phng php tch ring tch n
thnh hai i quang c.
Th d 2: Acid 2,3,4 - Trihidroxiglutaric (n = 3C*) c hai dng
quang hot v hai dng meso
C OOH COOH COOH C OOH
H OH H OH H OH HO H
Mpx H OH HO H H OH HO H
H OH H OH HO H H OH
C OOH COOH COOH C OOH
(I) (II) (III) (IV)
2 dang meso 2 dang quang hoat
Acid CH
lactic
3
Metyl -naphtyl phenylsilan
(1) (2)
H3 C
S
O
Ph
CH3
P .
OC H 3
CH3
a c
a c
C C C
C C C
b Q) d
b d P)
(a ( b) v (c ( d) (P) ( (Q)
ALEN
COOH HOOC
O2N NO2
HOOC COOH
NO2 O2N
Acid 6,6- dinitro-biphenyl- 2,2-dicarboxilic
Trong phn t biphenyl, hai nhn benzen c th quay t do
quanh trc Carbon - Carbon trung tm; nhng khi phn t c
mang nhm th c kch thc ln ti cc v tr (2, 6, 2, 6) th s
quay b cn tr, hai nhn benzen khng cn v tr cng phng do
tr ngi lp th pht sinh t nhng nhm th c kch thc ln
cc v tr orto, v th h phn t tr nn cng chc.
Thc t, ngi ta tch hai c hai dng i quang ca
acid trn.
* iu kin ch yu biphenyl th c tnh quang hot l cc
nhm th phi c kch thc kh ln cn tr s quay t do v
mi nhn benzen phi c th khng i xng. Ngoi ra, hai
nhm th orto khng cn phi gn trn hai nhn khc nhau.
Th d: 3,3- diamino - 2, 6 dibromo - 4, 4 - dimetyl
biphenyl cng c tch hai.
Br
NH2
H3 C C H3
H2N Br
c) Ankiliden ciclan:
Nu thay th mt ni i trong alen bng mt vng, v mt
hnh hc ca phn t khng thay i. Cc ankiliden mang nhng
nhm th thch hp c th c ng phn quang hc.
Th d: vi Acid 4 - metylciclohixiliden acetic c tch
hai thnh hai dng i quang :
H COOH HOOC H
H3 C H H CH3
HOOC
N .
Dn xut ca 4 - carboxiciclohexilidenimin
vi R: OH
NH C NH2
O
N C Ph
Ph O
d) Spiran: s thay th hai lin kt i trong Alen bng hai
vng dn n mt h vng c chung mt cnh (hai vng i
nh): Spiran. Nu hai vng mang nhng nhm th trn hai
nguyn t carbon ti hai u ca h nm trong hai mt phng
thng gc vi nhau th chng c ng phn quang hc.
Th d: Acid spiro [3,3] heptan - 2, 6 - dicarboxilic v 2, 6 -
diamino spiro [3,3] heptan
H H H H
R R R R
R = _ COOH hay _ NH2
2.6.1.3. Tnh quang hot do c mt phng khng trng
vt nh
Mt phng khng trng vt-nh c cc hp cht
ansa.
Th d: (A) * (R) - 14 Bromo - 1,12 - dioxa [12]
paraciclofan
(B) * (E) ciclo octen
u c mt phng khng trng vt-nh nm trong mt phng giy
O
Br
H H
(CH2)8
H H
O (R) (S)
(A) (B)
2.6.2. Tnh c th lp th ca cc qu trnh ha sinh
Cc i quang khng khc nhau v l tnh v ha tnh
thng thng nhng nhiu khi li khc nhau r rt v tc
dng sinh l.
Th d: (-) Nicotin c trong thuc l c hi hn (+) Nicotin
vi ln hoc cc i quang ca aminoacid c v khc nhau nh L-
asparagin v L-tritophan khng c mi v, cn L-leuxin v L-
Tyroxin c v ng trong khi cc ng phn D - tng hp c v
ngt.
Acid L-glutamic thin nhin c v ngt, mui Natri ca acid
L-glutamic l bt ngt (m chnh) dng lm gia v thc phm; cn
acid D-glutamic khng c c tnh y.
Do c tc dng sinh l khc nhau, cc i quang ca nhiu
hp cht c dng lm thuc cha bnh.
Th d: R (-) epinephrin thin nhin, mt hormon chnh ca
tuyn thng thn. Do khi cho ngi bnh ung epinephrin
tng hp, th ch R (-) epinephrin c hiu ng kch thch ging
nh hormon thin nhin, cn S (+) epinephrin khng c hiu ng
kch thch m li gy c nh.
Tnh c th lp th cng biu hin r cc hp cht bo v
thc vt. Th d trong tm ng phn ca C6H6Cl6 (6,6,6) ch c
ng phn ( c hot tnh tr su mnh.
Cl
*
Cl CH
Cl Cl CCl3
Cl X X
(C) (D)
Cl
ng phn ( _ ca 6,6,6 (D.D.T)
Hoc khi nghin cu mt lot cc ha cht tr su v kh
nng quay t do trong phn t kiu D.D.T, ngi ta nhn thy nu
cc hp cht kiu (D), cc nhm th X v tr orto lm gim tnh
tr su.
* Acid cis-cinamic kch thch mnh s tng trng ca cy,
trong khi acid trans-cinamic li khng c hot tnh y.
Nguyn nhn ca nhng khc nhau v hot tnh sinh l l s
khc nhau v cu trc khng gian (khc nhau v cu hnh) v c
th gii thch nh sau:
i) Cc i quang c th c phn b khc nhau
trong m t bo ca c th sng.
2i) Cc i quang c th c i lc khc nhau i vi c
quan th cm (Receptor). S khc nhau ny l do vi nhng i
quang no chng c kh nng tng tc c ch khng do tnh
cht bt i xng.
3i) Cc enzim trong c th sng u bt i xng nn
chng c kh nng phn bit cc i quang, thng thng ch mt
trong hai i quang l ph hp vi tm enzim.
2.7. BIN TH RACEMIC (dng tiu trin)
2.7.1. Bn cht ca bin th racemic
Bin th racemic (dng tiu trin) l mt hn hp
ng phn t (equimolar) ca hai ng phn i quang ca
mt cht c phn t bt i xng. Do tr s quay cc ca
tp hp ny bng khng. Thng c k hiu l () hay
D,L.
2.7.2. S to thnh bin th Racemic
2.7.2.1. Phng php trn ln
Phng php n gin nht iu ch cc bin th racemic
l trn k s lng ng phn t ca hai dng ng phn hu trin
(quay phi) v t trin (quay tri): qu trnh ny gn lin vi s
thay i Entropi bi v bin th racemic trng thi hn lon hn
cc i quang ring bit.
Entropi ca s trn ln: (S = - Rx1Lnx1 = Rx2Lnx2 (bin th
racemic: x1 = x2 = 1/2) ( (S = 5,8 ( J/mol. S thay i nng
lng t do khi to thnh bin th racemic t cc i quang s l
(F = - T(S = -1,755 KJ/mol nhit phng.
2.7.2.2. Phng php tng hp
Bng phng php tng hp cc phn t bt i xng, ngi
ta nhn c bin th racemic nu i t cc phn t i xng ny
t bin th racemic m khng dng tc nhn quang hot, xc tc
hay mt tng tc vt l bt i xng no.
COOH COOH COOH
P
2H C H + 2 Br2 Br C H + H C Br + 2 HBr
CH3 CH3 (+) CH3 (-)
O OH NC H OH
H H H CN H
+ HCN H +
H H H
H H H
* Phn ng cng HCN v acetaldehid (CH3-CHO) cho hn
hp hai i quang vi s lng bng nhau.
2.7.2.3. Phng php racemic ha
Php bin i mt dng i quang tinh khit ca mt cht
quang hot to thnh hn hp racemic tng ng gi l s
racemic ha. S racemic ha c th xy ra di nh hng ca
nhit, nh sng hay ha cht.
Tonng chy
0% 50%(+) 100%(+)
100%(-) 50%(-) 0%
( Gin Tonng chy ca dung dch racemic rn)
R1
muoi (+) (-) + HCl R-COOH (+) + R2 N HCl
ket tinh R3 (-)
phan oan R1
muoi (-) (-) + HCl R-COOH (-) + R2 NH Cl
R3 (-)
* *
(HOOC-CHOH-CHOH-COOH) Tartrat (+) (-A)
CH3 CH3
(+)A (-)A
Mui tartrat (+)(-A) tan trong CH3OH km hn mui tartrat
(+)(+A) do ng phn (+)(-A) kt tinh ngay di dng tinh
khit, nht l khi a vo dung dch vi tinh th mui (+)(-A) c
sn lm mm kt tinh. c mui hon ton tinh khit
thng phi kt tinh li mt ln trong H2O ri ph v mui ny
bng dung dch kim v tch ring (-) (-phenyletylamin ra khi
dung dch Natri tartrat. Bi v acid (+) tartric l mt tc nhn r
tin nn vic ti sinh tc nhn bt i xng trong trng hp ny
l khng cn thit.
c) Tch ring ancol:
Cc ancol racemic thng c tch ring thnh i quang
bng hai phng php sau:
- Este ha ancol racemic bng acid quang hot ri tch
ring cc este bng phng php kt tinh phn on.
- Este ha ancol bng diacid chuyn thnh bn este c
kh nng to mui vi cc baz quang hot.
Th d: tch ring hai ng phn (+), (-) ca ru Sec-
butylic ta tin hnh theo s sau:
O
OH
COOH
Piridin C 2 H5
H3 C C* C 2H5 + O
H C O C* H
Ru (+)(-) O
O CH3
_
+ Bruxin (*) COO
C 2 H5
Tach 2 chat H.Brunxin
C O *CH
(+) va (-)
CH3
(+) O a tinh che
COOH
+HCl C 2H5 + Bruxin.HCl
C O CH
CH3
O CH3
CH3 CH2OH
COONa hay
* H + + HO * H
HO +NaOH +LiAlH4
COONa dd CH2 OH
C 2H5 C 2H 5
Cng thc ca Bruxin
N
CH3O
CH3O N
O O
2.7.4.3. Phng php to phc phn t
Khi ch ha bin th racemic bng tc nhn bt i
m to thnh c phc tinh th th c th thu c hai phc
ng phn bn i quang khc nhau v ha tan v s c
mt ng phn kt ta trc. Sau ph v phc ny bng
cch un nng, ha tan, bng sc k hay ch ha ha hc ta
thu c mt trong hai i quang ban u.
2.7.4.4. Phng php sc k
tch ring bin th racemic () X thnh hai cht i quang,
ta cho () X qua ct nhi cht hp th bt i xng (vit tt l (-)
Chp), cc i quang to phc yu vi cht nhi bt i xng (nh
lin kt hidro) v ta c cc phc bn i quang (-) Chp (-) X v ()
Chp (+) X. Nhng phc ny c tnh cht vt l khc nhau, khc
nhau v nng lng lin kt, v hng s cn bng to phc, do
chng c bn khc nhau, ngha l mt cht i quang (t bn
vng) i qua ct nhi cht hp th bt i xng nhanh hn i
quang kia v nh vy hai i quang c tch ring.
Hin nay, phng php sc k c vai tr quan trng trong vic
iu ch hp cht quang hot v bao gm c ba loi: sc k lng,
sc k lp mng v sc k lng cao p.
Chng 3: NG PHN HNH HC
3.1. Bn cht ca ng phn hnh hc
3.2. Hp cht c ni i Carbon - Carbon
3.2.1. Danh php
3.2.2. Hp cht c mt ni i v nhiu ni i
3.2.3. Tnh cht vt l ca ng phn hnh hc
3.2.3.1. Momen lng cc
3.2.3.2. Nhit : nng chy, si, t khi v chit sut
3.2.3.3. phn ly ca acid
3.2.3.4. Ph: t ngoi, hng ngoi, cng hng t ht
nhn
3.2.4. bn tng i v s chuyn ha tng h gia cc
ng phn hnh hc
3.3. Hp cht c ni i C=N v N=N
3.4. Hp cht vng no
C
3.1. BN CHT CA NG PHN HNH HC
iu kin a ( b
a a
iu kin a ( b
C C (Q) cha lin kt (
b b (P) (Q)
P)
Q)
b cis b b trans a
(X) (Y)
Khong cch gia cc nguyn t trong phn t (X), (Y) khc
nhau rt ln, do v phng din hnh hc th (X), (Y) c hnh dng,
kch thc phn t khc nhau nn i lng Entalpi t do to thnh
cng khc nhau, cc hng s vt l, cc c trng v ph v cui cng
l tnh cht ha hc cng khc nhau r rt.
3.2. HP CHT C NI I
3.2.1. Danh php
- Nu hp cht mang mt ni i C=C, mang hai nhm hay ba
nhm th khc nhau, ta dng cu hnh:
CIS: ch hai nhm ging nhau ( hai nguyn t C) nm
cng mt pha i vi mt phng cha lin kt (
TRANS: ch hai nhm ging nhau nm hai pha i vi
mt phng cha lin kt (.
H 3C CH 3 H 3C H
H H H CH 3
cis but-2-en. trans but-2-en.
H 3C C 2H 5 H 3C H
H C 2H 5 C 2H 5
C 2H 5
trans-3-metylhex-3-en. cis-3-metylhex-3-en.
- Vi anken phc tp, cu hnh c chn l cu hnh ca
mch Carbon lin tc di nht xuyn qua lin kt i.
C H 3CH 2 C H 2CH 3 (mc d c hai nhm etyl nm
cng mt pha i vi mt
phng)
H 3C CH 2CH2CH 3
Trans-4-etyl-3-metylhept-3-en
- Nu anken mang bn nhm th khc nhau m khng chn
c mch chnh th dng danh php E-Z.
Th d:
H 3C Br 3H C Cl
C C C C
H C H Br
Z -1-Bromo-1-cloropropen
l E-1-Bromo-1-cloropropen
Th d 1: hepta-2,4-dien
CH3-CH=CH-CH=CH-C2H5 c bn ng phn hnh hc
H H CH3 H
C 2H 5 H
CH3 H
H H H C2H5
cis - 2 - cis - 4 trans - 2 - trans - 4
H H H3 C H
H C 2H 5
H3 C H
H C 2 H5 H H
cis - 2 - trans - 4 trans - 2 - cis - 4
Th d 2:
CH3-CH=CH-CH=CH-CH3 ch c ba ng phn hnh hc
H H C H3 H 3C H
H
H 3C H
H H H CH 3
cis - 2 - cis- 4. trans - 2 trans - 4 .
H3 C H
CH
H 3
H H
trans - 2 cis-4 ( hoac cis - 2 trans-4 )
Hp cht c ni i ly tch
Cumulen vi s chn ni i c ng phn quang hc.
Cumulen vi s l ni i c ng phn hnh hc.
a a
C C C C
b b
Th d: Nm 1959, Kuhn c lp c hai ng phn 1,4-
di-m-nitrophenyl-1,4-diphenylbuta.trien
NO 2
C C C C
NO 2 2 NO O 2N
Cis Trans
3.2.3. Tnh cht vt l ca ng phn hnh hc
3.2.3.1. Momen lng cc
Hp cht kiu abC = Cab nu lin kt C-a c momen
lng cc ln, lin kt C-b khng c momen lng cc th ng
phn cis phi c momen lng cc rt ln, mt khc ng phn
trans c trung tm i xng nn momen lng cc tng bng
khng.
Th d: 1,2 dicloroeten
Cl Cl H Cl
Cl H
Hcis = 1,89 DH trans = 0
Nu nhm a- y electron, cn nhm b- rt
electron th momen lng cc ca phn t bng tng s momen
lng cc ca chng. Do ng phn trans c gi tr momen
lng cc ln hn ca ng phn cis.
H Cl H3 C Cl
H3 C H H H
trans = 1,97 D cis = 1,71 D
Khi tnh Momen lng cc ca nhng anken mang nhm
th phc tp s gp nhiu kh khn.
H H H COOC 2H5
COOH HJ = 12,3HCps
JHH-H= 15,8 Cps H-H
Acid cinamic
3.2.4. bn tng i v s chuyn ha tng h gia
cc ng phn hnh hc
bn c th l v mt nhit ha hc v c o bi nhit
hnh thnh, hoc l v mt nhit ng hc c o bi nng lng
hnh thnh. Do s khc nhau v bn gia cc ng phn cis
v trans c th c biu din s khc nhau v Entalpi hay nng
lng t do.
C th o mc khc nhau v bn nhit ha hc ca cc
ng phn hnh hc bng cc i lng ca thiu nhit. Nhng
chnh xc ca phng php ny cng b hn ch, bi v cc thiu
nhit rt ln nhng s khc nhau ca chng th li nh.
V tnh bn nhit ng tng i ca cc ng phn hnh hc
c th d on theo nng lng t do hnh thnh nu bit c
nng lng ny.
Th d: nng lng t do hnh thnh ca trans-but-2-en 25oC
ln hn nng lng t do hnh thnh ca ng phn cis l 2,884
KJ/mol. Cn ch rng i lng ny nh hn hiu s tng ng ca
entalpi (3,971 KJ/mol) bi v cis-but-2-en c entalpi ln hn trans-but-
2-en l 4,347 kJ/mol.
Nng lng t do hnh thnh i vi nhiu i ng phn
hnh hc vn cn cha bit ht. Tuy vy, c hai ng phn trong
cn bng ha hc v t trng thi cn bng c tnh trc tip hiu
s nng lng t do.
Th d: trong hn hp cn bng ca cis-, trans-but-2-en
3900C cha 52,8% ng phn trans.
Phng php n gin nht c s chuyn ha tng h
ca cc ng phn hnh hc l un nng chng.
Th d: i vi Stilben hng ro nng lng ca s chuyn
ha tng h bng 167,2(188,1KJ
thc hin qu trnh ng phn ha cis-trans c th dng
cc xc tc khc nhau nh: gc t do, ngun sinh ra gc t do nh
NxOy, cc halogen (c mt nh sng), cc axit: HX (X: halogen),
H2SO4, BF3, kim loi kim (natri), tc nhn hidro ha,dehidro
ha nh Pt, Se.
Th d: s ng ha cis-trans vi xc tc gc t do:
R H
R Br Br
R + Br H R
H
R H R H
H
H
R + Br
R
Mun c Br(Hta dng Br2 vi nh sng c di sng tng
i ln (cc i hp th i vi Brom l 415A0)
3.3. HP CHT C NI I C=N HAY N=N
3.3.1. ng phn hnh hc ca Oxim
Aldoxim, cetoxim c ng phn hnh hc c gi l syn-
hay anti-
H3C
.. H3C OH
..
C N C N
OH
H
H
Syn Acetaldoxim Anti Acetaldoxim
(So snh v tr tng i gia nhm OH v H)
C N
Cetoxim: c ng phn hnh hc khi nguyn t carbon (sn
phm) lin kt vi hai nhm khc nhau.
H3C OH
..
C N
O
C N
CH3
H3C
phenyl p totyl N metylnitron
bng s kho st momen lng cc.
Phenyl hidrazon v semicarbazon
Phenyl hidrazon ca acid O-nitrophenyl glioxilic v
monosemicarbazon ca benzyl cng c ng phn hnh hc.
NO2
.. ..
C N C N
O
HOOC NH C NH-C-NH2
O
Phenylhidrazon Monosemicarbazon ca benzyl
ca Acid O nitrophenylglioxilic
3.3.3. ng phn hnh hc ca hp cht c ni i N=N
Diazoat
Ar
.. . ..
.. N
anti arildiazoat
N
O Ar
N
syn arildiazoat
N
O
.. .. Ar
..
Ar
N
syn
N
CN
.. N
anti
N
CN
Azobenzen
.. . ..
. N
=0
N
trans azobenzen
N
= 3D
cis azobenzen
N
O
N N
cis azoxibenzen
. trans azoxibenzen
N N
.
Khi un trn nhit nng chy, ng phn cis chuyn thnh
ng phn trans.
3.4. HP CHT VNG NO
Cc cicloankan mang nhng nhm th thch hp cng c ng
phn hnh hc.
CH3 CH3 H CH3
Cis H
1,2 dimetylciclopropan
H Trans 1,2
CH dimetylciclopropan
H
3
H H CH3
Cis cis Cis trans Trans trans
( Trans cis )
Chng 4: NG PHN CU TRNG
CA HP CHT KHNG VNG
1.
1.1. Khi nim v cu trng (conformation)
1.2. Php phn gii cu trng
1.3. Cu trng ca hidrocarbon no
1.3.1. Etan
1.3.2. nbutan
1.3.3. npentan
1.3.4. nhexan
1.4. Cu trng ca hidrocarbon no mang nhm th
1.4.1. Halogenur etyl
1.4.2. 1,2dicloroetan
1.4.3. Etanol mang nhm th v tr s 2
1.4.4. 2,3dibromobutan
1.5. Cu trng ca hp cht khng no
1.5.1. Hp cht c ni i C=O, C=C, N=C
1.5.2. Hp cht c ni i lin hp
1.5.3. S quay quanh ni i
4.1. KHI NIM V CU TRNG
Khi nim v cu trng dng ch cc dng hnh hc ca
phn t c to thnh do s quay quanh lin kt n m khng
b gy lin kt (nn cn gi l ng phn quay Rotamer)
V mt l thuyt, mt phn t c v s cu trng vi mc
nng lng khc nhau, ty theo bn cht ca cc nguyn t lin
kt cng ha tr v nh hng gia cc nguyn t khng lin kt
trong phn t, cu trng c coi l n nh nht ng vi mc
nng lng thp nht, khi tng tc gia cc nhm nguyn t
trong phn t t nht. Tuy nhin, v hiu s nng lng v thi
gian cc nguyn t ti nhng v tr khc nhau rt nh nn cc
cu trng khng th c lp c (tr vi trng hp c bit).
Th d: Acid mesotartric c hai cu trng (cng mt cu
hnh = Configuration)
OH HO COOH
HO
H
H H
HOOC H HOOC
C OO H OH
mat phang oi xng
tam oi xng
Hai cu trng ca acid Mesotartric
H H H
Nhn theo trcH CarbonCarbon, thyH Hcc ni CH
H ca mt
nguyn t carbon trong cu trng lch l nhng ng phn gic
ca cc gc HCH ca nguyn t carbon kia. Etan c ba cu trng
lch ging nhau, to thnh khi nhm metyl ca cu trng lch
quay 1200 quanh ni n CarbonCarbon.
Gc quay c xc nh chnh xc hn bi gc xon (gc nh
din), l gc gia hai mt phng:
1C C2
__ Gc xon __
mt mt phng xc nh bi mt ni CH ch nh ti nguyn t
Carbon s 1 vi ni C1C2 v mt phng th hai xc nh bi
mt ni CH ch nh ti nguyn t Carbon s 2 vi ni C2C1
Trong cu trng lch, gc xon ( = 600 cn trong cu trng
che khut gc xon ( = 00
Gc xon bin thin t 00 n 3600 khi nhm metyl quay
quanh lin kt CC.
S bin thin nng lng theo gc xon l mt ng cong
gn hnh sin vi ba cc i v ba cc tiu, cao ca ro nng
lng trong etan l 2,8 Kcal/mol.
Cu trng lch bn nht, v c mc nng lng ti thiu, cu
trng che khut ng vi mc nng lng cao nht nn khng bn.
Nh vy, bnh thng Etan c cu trng lch cn cu trng che
khut l mt trng thi chuyn tip to ra khi phn t Etan quay t
cu trng lch ny n cu trng lch khc.
V ro nng lng ca s quay kh thp, cc phn t c dy
h c coi nh quay t do quanh ni n, nhit thng.
4.3.3. npentan
Vi hai trc quay trong C2C3 v C3C4 th phn t n
pentan c th c tt c by cu trng (i lch v bn lch). Ph
Raman cho bit c hai cu trng tn ti trong npentan th lng,
cu trng u i c nhm CH3 v C2H5 i lch, k l cu
trng bn lch. Hiu s nng lng gia hai cu trng c chng
0,5 0,7 Kcal/mol. Cc cu trng khc cha nhiu dng bn lch
hn do t bn hn.
CH3
CH3 H H
H H
CH3
C H H
H H
C CH3
H trngHi lch ca npentan
Cu
H CHH
3
CH3 H H
H H
H
C H H
H H
C H
H3C H
H3C
Cu trng bn lch ca npentan H
4.3.4. nhexan
Phn t nhexan c ba trc quay trong v c th c 12 cu
trng, cu trng i lch chim ( nhiu nht trong cn bng, tng
t npentan, phn t nhexan cng c hiu s nng lng gia
cu trng i lch v bn lch c chng 0,5 Kcal/mol.
H
H H H H
C
H H
H
H trngHi lch
H trong nhexan H H
H Cu
Theo ph Raman, nankan c 12 nguyn t Carbon c cu
trng hon ton i lch trng thi kt tinh. Tuy nhin, trng
thi lng c mt s cu trng bn lch ng k ti bt c ni no
v bt c lc no. Hiu s nng lng gia cu trng i lch v
bn lch c chng 0,8 Kcal/mol.
4.4. CU TRNG CA HIDROCARBON NO MANG
NHM TH
4.4.1. Halogenur etyl
S thay th mt nguyn t Hidro trong etan bng mt nguyn
t Halogen khng lm thay i ro nng lng mt cch ng k.
Dng phng php ph nghim, ngi ta tm thy tr s ro nng
lng nh sau:
CH3CH2F CH3CH2Cl CH3CH2Br
3,33 3,50 3,50 (Kcal/mol)
4.4.2. 1,2dicloroetan
Vi cc phn t phc tp, ngi ta cn xt n nhng tng
tc khc hn tng tc lp th nh: tng tc lng cc, lc ni
hidrogen ni phn t
Phn t 1,2dicloroetan c cu trng bn lch km bn hn
cu trng i lch, do lc x y lng cc mnh hn, mc d
tng tc lp th km bn hn trong nbutan.
Cl Cl
H H H Cl
H H H H
i
Cl lch Bn
H lch
Cu trng ca 1,2
dicloroetan
Nhiu x tia X chng minh 1,2dicloroetan kt
tinh hon ton di cu trng i lch.
Ph hng ngoi v Raman cho thy 1,2
dicloroetan trng thi rn c mt tm i xng, nh vy tn ti
di cu trng i lch, khi ha lng mt s phn t bin i
thnh cu trng bn lch (c chng minh bng s gia tng s
vch trong ph hng ngoi v Raman)
Nhiu x in t cho thy 1,2dicloroetan trng
thi kh cha 73( cu trng i lch v 27( cu trng bn lch (
220C), hiu s nng lng gia hai cu trng ny khong 1,03
1,32 Kcal/mol.
Momen lng cc ca cu trng u i c tr s
bng 0 (cu trng i lch). Thc nghim cho bit momen lng
cc tht s ca 1,2dicloroetan thay i theo nhit t 1,12 D
320C n 1,54 D 2700C, s kin ny ph hp vi mt cn bng
gia cc cu trng i lch v bn lch.
4.4.3. Etanol mang nhm th v tr s 2
RCH2CH2OH
R: OH, NH2, F, Cl, Br, OCH3, NO2, NHCH3
Thng thng cu trng i lch bn hn cu trng bn lch.
Tuy nhin, t l n nh c th o ngc vi mt s hp cht c
c cu c bit.
Th d: cu trng bn lch ca etylen clorhidrin bn hn cu
trng i lch bt c iu kin no, th rn ch c cu trng
bn lch tn ti; th lng hoc kh, mt cn bng c thit lp
gia cu trng bn lch v i lch, nng lng ca cu trng bn
lch thp hn nng lng ca cu trng i lch 0,95 Kcal/mol do
cu trng bn lch c lin kt Hidro ni phn t.
Cl
H
...H
Cl
H H O
H H H
iH lch
OH
Bn
H
lch
Cu trng ca
Etylenclohidrin
Tng qut, tt c cc RCH2CH2OH vi R l OH,
NH2, F, Cl, Br, OCH3, NO2, NHCH3 u c cu trng
bn lch n nh hn cu trng i lch nh lin kt hidro ni
phn t gia nhm R vi OH, mc d c s x y lp th v
lng cc gia hai nhm ny.
4.4.4. 2,3dibromobutan
2,3dibromobutan c hai ng phn: Eritro (cng l Meso) v
Treo.
Nhiu x in t cho bit ng phn Meso tn ti di cu
trng i lch A; cn ng phn Treo tn ti di cu trng B c
hai nguyn t Brom i lch nhau, hai nhm CH3 bn lch
Br Br Br
H CH3 Br H H3C Br
Br Br Br
H3C Br H Br
H CH3
H3C H H H3C H
H3C
Br H CH3
treo (B) (B1) (B2)
H H H H H H
H H H
CH3CHO CH3CH=CH2 CH3CH2CHO
Trong phn t propanal, xc nh bi hng s ghp cng
hng t ht nhn nhm CH3 che khut ni i C=O. Kt qu
ny c th gii thch bi sc ht lng cc gia CCH3 vi
C=O. O O
H C OCH3 H C OCH3
Vi cc phn t ; CH3OCH=CH2 ;
th cu trng u i ng vi ni i C=O, C=C, C=N u che
khut nhm CH3. iu ny c chng minh bi ph hng
ngoi, ph viba v nhiu x in t.
H H
C O C O
O H2C
Metyl formiat CH3 Metyl vinyl eter CH3
Cu trng u i ca formaldoxim c ni i C=N v ni OH
i nhau. H
N O
H2C
iu ny c th c gii thch bi s x y gia electron p
v ( trong metyl formiat, metyl vinyl eter ; v gia in t p trong
formaldoxim.
4.5.2. Phn t c ni i lin hp
Phn t c ni i lin hp c th c ng phn cu trng,
l ng phn Scis v Strans (Single: n). Tip u ng S t
trc ch cis v trans ch cu trng lin h n ni n trong
h lin hp.
H H H CH2
S_cis S_trans
Cu trng ca buta-
1,3-dien
Kt qu thc nghim da trn tnh cht nhit ng hc, nhiu
x in t, ph nghim hng ngoi v viba cho bit cu trng S
trans ca buta-1,3-dien bn hn cu trng Scis t nht 2
Kcal/mol.
Ngoi ra, ph hng ngoi v Raman chng minh trans-
pent-3-en-2-on l mt hn hp cn bng cha cu trng Scis v
Strans vi s lng bng nhau.
H
C CH3
O O H
+ HBr CH3-CH2-CH2Br
_ Khc hn vi propen, ciclopropan khng b oxi ha bi dung
dch KMnO4.
Ciclobutan t c khuynh hng cho phn ng cng
hn ciclopropan, nhng c th hidrogen ha vi xc tc Ni,
1800C cho nbutan.
t0 CH3-CH2-CH2-CH2I
+ HI
_ Vi Br2, HBr, KMnO4 cng khng tc dng vi ciclobutan.
5.1.2. Thuyt cng Baeyer
Baeyer gi s cicloankan l nhng a gic u v phng v
tnh lch ca gc ni trong cc cicloankan i vi t din bnh
thng.
lch ca ( mi gc ni trong vng gi l sc cng gc hay
sc cng Baeyer.
1
= (109,5o )
2
* ( l gc trong ca vng
* H s gii thch s
phn phi sc cng ng u
gia hai ni lin h
n = s cnh ca vng
lch gc ca cicloankan
N n
0
3 60 +24,7 11 147,3 18,8
4 900 +9,7 12 150 20,3
5 1080 +0,7 13 152 21,5
6 1200 5,3 14 154,3 22,4
7 128,6 9,6 15 156 23,3
8 135 12,8 16 157,5 24
9 140 15,3 17 159 24,7
10 144 17,3
(2) H/n (Kcal/mol): thiu nhit tnh cho mi nhm CH2 ca hp cht
cicloankan ( th kh)
(3) (H/n157) Kcal/mol: hiu s thiu nhit tnh cho mi nhm CH2
ca cicloankan v nankan tng ng
(4) Tng s sc cng ca ciclan
dng gh dng tu
Cu trng ca ciclohexan
Nm 1918, Mohr gii thch rng hai dng gh v tu bin i
ln nhau rt nhanh nn khng th c lp c.
5.1.5. Sc cng Pitzer
Nng lng ca cc hp cht vng gia tng vi sc cng
Baeyer do s bin dng ca gc ha tr.
Nng lng cng c th gia tng bi s to thnh mt cu
trng c dung tch nng lng bt li. S gia tng nng lng khi
mt cu trng lch thun li bin i thnh mt cu trng che
khut bt thun li, gi l sc cng Pitzer trong phn t.
Sc cng Pitzer do s x y gia cc nguyn t k cn khng
ni cn gi l sc cng i ni hay sc cng xon.
Sc cng Pitzer tr nn ng k i vi cc vng nh trong
cc nhm tr hon bt buc phi che khut nhau. Th d sc cng
Pitzer lm cho ciclopentan khng th c c cu phng ng thi
bin dng gc t din, ngha l a n sc cng Baeyer. Mc d
s kin ny gia tng nng lng, dng khng phng ca
ciclopentan c th nng thp hn th nng ca dng phng, v cu
trng tng ng thun li hn v mt nng lng.
5.2. CU TRNG CA CC VNG NH
5.2.1. Ciclopropan H H
H
H H
H
Ciclopropan
Vi ba nguyn t Carbon trong vng, ciclopropan c c cu
phng, gc trong ca ciclopropan bng 600 nn phn t ht sc
cng, do ciclopropan rt d m vng. Ngoi ra cc ni CH
cng mt bn mt phng che khut nhau, lm cho phn t cng
khng bn.
1
R
5
4
3 2
H3C H3C
. () ()
(e)
Trc i xng bc 3
Ni trc (a) Ni xch o (e)
(a)
5 3
1 (e)
6
5 1
4 2
4 3 (e)
2 6
(a)
( hnh chiu Newman)
Cu trng gh ca ciclohexan
1.84A0
fp
fp H H fp
bs bs
1 bs 1
4 5 6 6 2
2.49A0
eb 4
5 3
3 2
ab
2.27A0
nhn bn nhn dc
Khong cch gia cc nguyn t Hidro gn trn hai nguyn t
C gn nhau trong cu trng tu ca ciclohexan
Kiu V tr Khong cch A0
Ct c 1fp 4fp 1,84
Che khut 2eb 3eb 2,27
2ab 3ab 2,27
Bn lch 1bs 2eb 2,49
1bs 2ab 2,49
1fp 2eb 2,49
Trans 2ab 3eb 3,00
Nh trc 1fp 2ab 3,00
fp
1 bs
eb 4
4 1 eb
5 6 eb bs eb
6 3
5 2
3 2
abab ab a
b
Cu trng tu Hnh chiu Newman ca
cu trng tu
H
H
1 5 2
H 4 H H H
5
2 4 1
H 3 6 H
3 6
Cu trng tu xon ca ciclohexan
X
H 2,55A0
H
H 2,8A0
H
a) Ankylciclohexan
_ Metylciclohexan
Khi nhm CH3 v tr xch o, khong cch
gia cc nguyn t Hidro ca CH3 v cc nguyn t Hidro gn
nht ca vng l 2,5A0, ngha l ln hn tng s bn knh Van
Der Waals ca hai nguyn t H (2,4A0).
Khi nhm CH3 v tr trc, mt nguyn t H ca
nhm ny (hng v vng) gn cc nguyn t H trc ca vng
c chng 1,8A0 nn nhm CH3 (a) phi chu sc y Van Der
Waals; sc y ny tng ng vi s tng tc nbutan bn lch.
Do , mun bit metylciclohexan c cu trng no bn nht,
ngi ta so snh tng s n v butan i lch v butan bn lch
trong hai cu trng.
Metylciclohexan trc c hai tng tc butan bn
lch, cn metylciclohexan xch o c hai tng tc butan i
lch nn ng phn xch o bn hn ng phn trc khong 1,6 (
1,8 Kcal/mol. Kt qu ny c xc nh bi ph cng hng t
ht nhn, nhit thng hn hp cn bng cha 95% CH3 (e)
v 5% CH3 (a).
- Khi nhm th l C2H5, isoC3H7 th cu trng
xch o vn bn hn cu trng trc.
- Nhm th tertbutyl khc hn nhm ankyl khc,
nu But(a) th mt trong ba nhm CH3 bt buc phi hng v
vng v gy ra s tng tc vi hai nhm CH2 v tr 3 v 5 c
tr s ln hn 5 Kcal/mol. Nng lng ny qu cao nn tertbutyl
khng th v tr trc trong cu trng gh nn n ch tn ti v
tr xch o.
H3C CH3
H
CH3
H
CH3
CH3
Nhm tertbutyl trc Nhm tertbutyl
CH3 xch
o
Cu trng ca tertbutyl ciclohexan
b) Ciclohexanol
Ciclohexanol tn ti di cu trng vi nhm OH xch o
(6290%)
OH
Cu trng ca ciclohexanol OH
c) Halogenociclohexan
Theo nhiu x in t v nhiu x tia X hay php o momen
lng cc, cu trng u i ca clorociclohexan trng thi kh
c nguyn t Clor v tr xch o (55%60%). Hiu s nng
lng gia hai cu trng l 0,3 0,4 Kcal/mol, chng minh c
khong 40% cu trng trc trong hn hp cn bng.
trng thi lng, c hai cu trng trc v xch o u c mt
i vi clorociclohexan v bromociclohexan, ph hng ngoi cho
bit thm c 40% cu trng trc tn ti trong hn hp cn bng,
hiu s nng lng gia cu trng xch o v cu trng trc c
c lng l 0,3 0,5 Kcal/mol bi ph cng hng t ht nhn.
Nhm Go Nhm Go
CLVT 0,40 NH2 1,21,8
Br 0,50 COOH 1,2
I 0,4 COOCH3 1,1
OH 0,60,9 CN 0,2
OCH3 0,7 CH3 1,7
OCOCH3 0,7 C2H5 1,8
OTs 0,7 Pri 2,1
SH 0,9 Bu 2,1
SPh 0,8 But 5,6
Ph 3,1
Hiu s nng lng t do cu trng trong ciclohexan
mang nhm th ((Go : Kcal/mol)
i vi nhm OH, NH2: tr s nh ng vi dung mi
khng cha H+; tr s ln ng vi dung mi c proton.
5.3.3.2. Ciclohexan mang hai nhm th
5.3.3.2.1. Diankylciclohexan
a) Dimetylciclohexan
1,1dimetylciclohexan (ch c mt cu trng)
CH3
CH3
Trans ee Trans aa CH
3
CH3
HC3
CH3
cis ea cis ae CH3
Cu trng cis ea c ba tng tc butan bn lch ng vi 2,55
Kcal/mol.
nhit thng, 1,2dimetylciclohexan tn ti gn nh
hon ton (99%) di cu trng ee.
1,3dimetylciclohexan c ba ng phn cu trng.
H3C CH3
Cis ee Cis CH
aa 3
CH3
CH3
H3C
CH3
Trans ea Trans ae
CH3
- Cu trng cis ee khng c tng tc butan bn lch.
- Cu trng cis aa c mt tng tc nh trc (3,7
Kcal/mol) v hai tng tc butan bn lch (1,7 Kcal/mol)
Gaa = 3,7 + 1,7 = 5,4 Kcal/mol
- Cu trng trans ea c hai tng tc butan bn lch ng
vi 1,7 Kcal/mol.
1,4dimetylciclohexan c ba ng phn cu trng
CH3
CH3
H3C
CH3
Trans ee Trans aa
CH3
H3C
CH3 CH3
Cis ea Cis ae
- Cu trng trans ee bn nht v khng c tng tc butan
bn lch.
- Cu trng cis ea c hai tng tc butan bn lch.
- Cu trng trans aa c bn tng tc butan bn lch.
Nn nhit thng, 1,4dimetylciclohexan tn ti hon
ton di cu trng ee.
Khi hai nhm th khc nhau: A ( B th cu trng n nh nht
ng vi nhm th to v tr e.
b) Ciclohexan mang nhm ankyl ln
Nu hai nhm th u c kch thc ln nh tbutyl phn
ng gp ca cu trng mm do tr nn ng k.
Th d: 1,3ditert butylciclohexan
* Cis ee
H3C
CH3
H3C
H3C CH3
CH3
* Trans ae khng th tn ti cu trng gh v c nhm tert
butyl v tr trc gy tng tc nh trc rt ln, nn cu trng gh
chuyn sang tu xon c hai nhm tbutyl u v tr e.
H3C
H3C
H3C CH3
CH3
Cu trng tu xon CH3
5.3.3.2.2. Dihalociclohexan
1,2dibromociclohexan
Br
Br
Br
Br
=0
= 3,1 D
(60%) Trans ee Trans aa (40%)
Bnh thng ng phn trans ee bn hn trans aa nhng
momen lng cc cho thy c hai cu trng ee v aa u hin din
trong dung dch.
_ Momen lng cc ca trans aa = 0 (tnh
_ Momen lng cc ca trans ee = 3,1 D ton)
Momen thc nghim ty thuc vo dung mi s dng
+ Trong benzen ee = 2,1 D
+ Trong CCl4 ee = 1,7 D
Cu trng cis ee thun li v mt lp th nhng c s x y
lng cc gia 2 nguyn t Brom; nhiu x in t cho bit hn
hp cn bng ca hp cht trans1,2dibromociclohexan th kh
cha khong 60% cu trng ee v 40% cu trng aa.
Br
Br
( = 3,1 D) CisBr
ea Cis ae ( = 3,1 D) Br
Momen lng cc tnh cho cis1,2dibromociclohexan c gi
tr bng 3,1 D ((trans) v khng ty thuc vo dung mi.
(Tr s thc nghim = tr s l thuyt)
1,2diclorociclohexan
Momen lng cc tm thy dng trans ee l 2,6 D trong
benzen; 2,2 D trong CCl4 (momen tnh vn l 3,1 D).
ng phn cis ae c gi tr thc nghim v l thuyt u bng
3,1 D.
Nh vy momen lng cc ca hp cht trans1,2
diclorociclohexan ln hn ca trans1,2dibromociclohexan,
ngha l cn bng cu trng vi hp cht dicloro ciclohexan cha
t cu trng aa hn hp cht dibromo ciclohexan.
Cc kt qu v momen lng cc ca 1,2dihalociclohexan
c xc nhn bi ph Raman v ph hng ngoi.
- trng thi lng, trans1,2diclorociclohexan c khong
50% cu trng ee; cn 1,2dibromociclohexan c khong 40%
cu trng trans ee.
- Ph cng hng t ht nhn cho bit trans1,2
dibromociclohexan c khong 30% cu trng ee trong dung mi
khng cc.
- Ph Raman v hng ngoi chng minh rng trng thi
rn, trans1,2diclorociclohexan c cu trng ee; cn trans1,2
dibromociclohexan c cu trng aa.
1,3dihalociclohexan: c cu trng ee u i hn aa
1,4dihalociclohexen
trng thi kh, 1,4diclorociclohexan v 1,4
dibromociclohexan u cha cu trng ee v cu trng aa vi s
lng gn bng nhau.
trng thi rn, ch c cu trng ee tn ti.
trng thi lng c hai cu trng u hin din
5.3.3.3. Ciclohexan mang nhiu nhm th
Ciclohexan th v tr: 1,2,3 ; 1,2,4 hay 1,3,5 c th c
bn ng phn cu hnh: ciscis; cistrans; transtrans;
transcis. Ngoi ra mi ng phn cu hnh c th c hai cu
trng nn mi ng phn ciclohexan mang ba nhm th khc
nhau c th c tm ng phn cu trng.
Cu hnh Cu trng
Transcis eA; eB; eC aA; aB; aC
Ciscis eA; aB; eC aA; eB; aC
Transtrans eA; eB; aC aA; aB; eC
Cistrans eA; aB; aC aA; eB; eC
1A; 2B; 3C ciclohexan
HO
Mentol Neomentol
eee (Trans trans) eae (Cis trans)
CH3 CH3
OH
HO
Isomentol Neoisomentol
eea (Trans cis) eaa (Cis cis)
CH3
CH3
OH
CH3 CH3
OH
6 5 4
10 3
H
5 H 4
7 9
10 2
6 3
8 H 1
Transdecalin c hai vng ciclohexan dung hp vi nhau hai
ni xch o, l mt phn t cng rn, vi mt tm i xng (
ngay gia hai nguyn t C9C10) v mt trc i xng bc II
(xuyn qua gia C2C3, C9C10, C6C7)
Transdecalin khng th nghch chuyn thnh dng i hnh
v s dung hp hai vng ciclohexan gh ch xy ra vi hai ni ee
v khng th thc hin vi hai ni aa. Nn transdecalin l mt
phn t khng c tnh trin quang.
CISDECALIN:
H
H 9
H 1 2
9
7 8 H 8
1 4
5 10 10 3
6 2 7
6
5
4 3
4
9 2
10 3
8
1
7 5
6
Cisdecalin dung hp vi nhau bi mt ni xch o v mt
ni trc, cisdecalin c trc i xng bc II (xuyn qua gia C9
C10 v thng gc vi ni ny, trong mt phng phn gic gc nh
din gia hai nguyn t Hidro 9 v 10).
Cisdecalin l mt phn t mm do, bt i xng, c th bin
i d dng thnh dng i hnh (nh cisdimetylciclohexan).
Cisdecalin l mt cp (() khng th tch hai c.
Cu trng cisdecalin c ba tng tc butan bn lch, cn
transdecalin khng c tng tc butan bn lch. Nh vy, cis
decalin km bn hn transdecalin, hiu s nng lng gia hai
ng phn l 3 ( 0,85 = 2,55 Kcal/mol.
Cn bng gia cis v trans l thuc nhit , s kho st cn
bng ny nhit cao, xc tc Pt a n hiu s nng lng
trng thi lng l 2,72 Kcal/mol, ph hp vi tr s tnh.
DECALOL
Decalin mang nhm th v tr 1; 2 tn ti di bn dng
ng phn lp th: ciscis; cistrans; transcis; transtrans.
Cu hnh ca bn dng Racemic ca 1decalol v ca bn
dng Racemic ca 2decalol c xc nh dt khot bi
phng php: iu ch, ha tnh v l tnh. Nhng s phn gii
cu trng da trn cc d kin ng hc (x phng ha ester
carboxilat); dung mi gii ester sufonic v ph hng ngoi c
phn phc tp.
* TRANSDECALOL: cu trng cng rn ca
trans 1 v 2decalol.
H H H OH
H
H HO H
H(A) H (B)
Transcis1decalol Transtrans1
decalol
ng phn transcis1decalol c ba tng tc nh trc
1,3 gia nhm OH vi cc H(a) ti C3, C8, C10.
ng phn transtrans1decalol c mt tng tc peri
vi nguyn t H(e) ti C8, tng ng vi mt tng tc
nh trc 1,3.
H H OH
H
H
OH
(C) (D)
H H
Transcis2decalol Transtrans2decalol
Cu trng cng rn ca trans2decalol
(T) (Z)
OH HO
H H
(E) (F)
Ciscis2decalol
H OH OH
H
H H
H H
(G) (H)
Cistrans2decalol
Vn tc x phng ha cc hidrogen sucinat cis1 v 2decalil
bi NaOH trong H2O, 400C gim dn theo th t:
Ciscis2 cistrans2 ciscis1 cistrans1
1,16 0,70 0,45 0,13
Kt qu thc nghim hp l, v tnh linh ng ca chng, cc
ester cisdecalil l nhng hn hp cn bng gia cu trng vi
nhm OH (e) (nhiu) v cu trng vi nhm OH (a) (t) nn s
x phng ha xy ra chm hn mt ester xch o thun ty.
Ngoi ra, ng phn ciscis1 b chng ngi lp th gy ra bi
nguyn t Hidro ti C9.
H
CISHIDRINDAN: c hai vng sc hp bi mt
ni xch o v mt ni trc.
5.4.2.1. 8metylhidrindan:
CH3 CH3
6 8
7 1
H
5 4 CH3
9 3 2
trans cis (metyltrc) cis (metylxch o)
Dng Stroid Dng khng Stroid
(A) (B)
H ciscis H
6 8 H
7 1 5 9
H HO 4 3
H
5 4 H
9 2 6 7
OH 8 2
(C) 3 (D) 1
H OH H
1
HO H H
5 4 H
H 2 cistrans
3 ca Cishidrindan5ol
Cu trng
H3C CH3
Ge* Ge*
H H
Ph Ph
Metyl - - naphtyl phenyl germani
R R'' R'' R
R' R'
Cc amin bc II hay bc III ng l phi c tnh quang
hot do s bt i xng ca phn t, nhng vic tch hai
ng phn i quang u khng c kt qu do s chuyn rt
nhanh t dng ny sang dng khc (s racemic ha), trong
nhng phn t ny, nguyn t Nit dao ng gia nhng mt
phng ca ba nhm th, v nh vy vic chuyn t mt i
quang ny sang mt i quang khc phi qua mt trng thi
trung gian c dng phng:
N
N R R''
R R''
N R'
R'' R
R R''
R' N R'
R'
Nng lng hot ha cn thit quay cu hnh ca mt ng
phn quang hc bn nhit phng l 104,5 KJ/mol. Trong ph
hng ngoi ca NH3, c nhng vch trng ln nhau trong s dao
ng ca nguyn t Nit (400 ln/giy) qua mt phng cha cc
nguyn t Hidro vi nng lng chuyn ha l 22,75 KJ/mol (i
vi amin bc III cng c nng lng tng ng) nn vic tch cc
amin trn thnh hai i quang l khng thc hin c.
H3C
O
H3C N
N CH3 HOOC CH2
H3C
HO3S
H3C
bt i xng, nhng hp cht kiu ny c iu ch v tch
ring thnh hai dng i quang bi Minc (1937) v Adam (1949)
N N
H2C CH CH2 CH2 CH2 H2C HC CH2
X P X
X
X
X X
P ha tr 3 P ha tr 4
X
X
X X X
X P P
X X
X
X
X
P ha tr 5 P ha tr 6
Cu hnh khng gian ca Phosphor
Phosphin bc 3 vi nhng gc th khc nhau c th c tnh
quang hot do s c mt trong phn t mt nguyn t phosphor
bt i (k c orbital cha hai electron t do).
Ngi ta iu ch c phosphin quang hot, th d tch
ring metylnpropylphenyl phosphin thnh nhng i quang
bn vng. Khi lm vic vi ng phn quay phi th ngi ta thy
c s racemic ha rt chm trong toluen.
Tng t nh aminoxid, ngi ta c th iu ch
phosphinoxid mt cch d dng bng tc dng ca oxi ln
phosphin bc 3, n c tnh quang hot do cu trc t din ca
phosphor ha tr 4.
Ngi ta dng acid (+) bromocamphorsulfonic tch
metyletylphenyl phosphin oxit thnh cc i quang.
Cc phosphin bc 3 phn ng d dng vi lu hunh dn n
nhng phosphin sulfua c cu trc ging nh ca phosphin oxit.
Nm1944, W.C.Davies thnh cng trong vic tch thnh
cc i quang phosphin sulfua bc 3 (n-C4H9)(C6H5-) (p-HOOC-
CH2-O-C6H4-) PS vi [(]p=+9,6 v -9,7; tng t cc mui bc 4
ca phosphoni vi nhng gc khc nhau ging nh mui amoni
bc 4 tn ti di dng nhng ng phn quang hc do cu trc t
din ca phosphor ha tr 4.
P P
H3C CH3
R O R O R R''
(I)
R' OR'
(II) R'
(III)
S nh hng khng gian ca lu hunh trong cc hp cht
(I) Sulfoxid, (II) Ester ca acid sulfinic, (III) mui sulfoni
S
. PtCl6
2-
H3C
H5C2
Cloroplatinat carboximetyletylmetyl sulfonium
Selen v telur cng c nhng hp cht ging lu
hunh do n cng c nhng loi ng phn khng gian
tng t lu hunh.
6.2. HA HC LP TH CA POLYMER
6.2.1. Polyetylen (P.E); polyvinylclorua (PVC).
Trong polymer xut hin nhiu tm Carbon bt i
(nh PVC, polystyren, polyvinylacetat) khng c cu to
tinh th, do cu hnh bt thng ca nhng tm bt i. V
s xut hin nhng tm bt i trong phn t nn c hin
tng ng phn quang hc. C ba dng:
Polymer isotartic: tt c tm Carbon bt i c cng
cu hnh.
Polymer syndiotartic: cu hnh ca cc Carbon bt i
lun phin xen k.
Polymer atartic: cu hnh ca cc tm Carbon bt i
ngu nhin.
Polymer iu ha lp th (isotartic, syndiotartic) c t khi ln
hn, tan chy cao hn, ha tan thp hn polymer khng
iu ha lp th (atartic) v thng c th ko si c.
Cc polymer iu ha lp th c cu to tinh th th polymer
atartic c cu to v nh hnh.
R R R R R
Isotartic
R R R
Syndiotartic
R R R
R R
Atartic
R R R
Polymer c th c nhng on mch (vi chiu di ng k) l
isotartic lun phin vi nhng on mch atartic hoc
syndiotartic, nhng polymer kiu ny gi l polymer
stereoblock (polymer khi lp th).
6.2.2. Cao su
Trong s trng hp butadien-1,3 c th thu c
polymer-1,2-olefin isotartic v syndiotartic,
CH CH 2
n
CH CH2
hay polymer 1,4-(-CH2-CH=CH-CH2-)n. V phn t c lin kt
i, nn c ng phn hnh hc, polymer c th c cu hnh ton
cis- hoc ton trans- hay hn hp ca c hai loi.
CH2 CH2 H
CH2
H H H CH2
n n
Cis polybuta 1,4-dien Trans poly buta-1,4-dien
Polybuta-1,4-dien Polybuta-1,2-dien
Isotartic Syndiotartic
CH2 CH2 H
CH2
6.2.3.2. Disacarid
Disacarid l nhng glucid cu to bi hai n v
monosacarid, do disacarid lm mt glucosid trong
phn t th hai lin kt vi nhm hidroxiglucosid ca phn
t th nht.
Nu nhm ny l mt nhm OH khc hn nhm
OH glucosid th disacarid c tnh kh v tnh a trin.
Th d: maltoz hay 4-0-((-D-glucopiranosil)-(-D-glucopiranoz;
Lactoz hay 4 0 ( D galactopiranosil)
Dglucopiranoz.
HOH2C
O
2
HO 1
HO HOH2C
OH O
3
O 4 2
HO 1
3 OH (hidroxiglucosid)
Maltoz OH *
( )
6
HOH2C O 3 OH 1
2 HO
HO 4 5 O 4 5 *
HO 2 OH
OH 1 O
3 HOH2C
6
Lactoz
Nu hai nhm hidroxiglucosid ca hai loi ng
(monosacarid) kt hp vi nhau th disacarid to thnh khng c
tnh kh.
Th d:
+ Sacaroz (sucroz) hay D
glucopiranosil(Dfructofuranosid hoc (D
fructofuranosilDglucopiranosid.
+ Trehaloz hay -D-glucopiranosil--D-glucopiranosid.
HOH2C O ( )
1
CH2OH O
HO 5
HO HO
HO O 2
() 3 CH OH
4 6 2
OH
Sacaroz
HOH2C O
HO
HO ()
HO 1 OH
O ()
O 2
3
TREHALOZ 5
OH
4
HOH2C6
HO
6.2.3.3. Polysacarid
6.2.3.3.1. Celuloz
Celuloz c to thnh do nhiu n v ( D glucoz
ti v tr 1 ca vng th I v v tr 4 ca vng th II
OH 1 HOH2C
4'
HO O () OH ()
... O 4
O
O
HO
1' O
HO
O
...
HOH2C
OH O
HOH2C
6.2.3.3.2. Tinh bt
Tinh bt c to thnh do nhiu n v (D
glucoz gm hai loi:
Amyloz (20%) tan trong nc, s kt hp ti
v tr 1,4 ca (Dglucopiranoz c c cu thng.
Amylozpectin (80%) khng tan trong nc,
nguyn t C1 ca mi dy amyloz (gm khong 20-25 n v (
Dglucoz) lin kt vi dy k tip nguyn t Carbon s 6 nn
amylozpectin c c cu nhnh.
Cc sinh vt cng tn tr glucoz trong nhng cht
gi l glicogen. C cu ca glicogen ging amylozpectin hn
amyloz nhng cc dy ngn hn (12-18 n v glucoz) v c
nhiu nhnh hn (lin kt 1,4 v 1,6glucosid)
HOH2C O
...HO
O
CH2OH O
HOH2C
HO ( )
O
HO
Amyloz
HO
O HO HO
O
...
H O 2HC
O
H O 2HC
O
O
H O 2HC
O
O
H O 2HC
O
O
Amyloz pectin
6.3. HA HC LP TH CA STROID
Steroid to thnh mt nhm hp cht thin nhin rt phong
ph, trch ly t ng vt v thc vt, nh sterol (colesterol), acid
mt (acid colic,acid litocolic), kch thch t thuc phi tnh
(estron, progesteron), kch thch t v thng thn (cortison,
aldosteron), glucosid tr tim, sapogenin, alcaloid steroid
6.3.1. Sn cn bn
Sn cn bn chung l perhidrociclopentanophenatren, c su
nguyn t Carbon bt i xng: C5, C8, C9, C10, C13 v C14.
12
13 17
11
1 C D 16
10 9
2 8 14 15
A B
3 5 7
4 6
Cc nhm th thng c mt trong sn cn bn ca
steroid thin nhin l:
- Mt nhm -CH3 ti C10 ; C13
- Mt dy nhnh ankyl ti C17.
Trong vi trng hp nhm CH3 ti C10 v C13 c th thay
bng nhm formyl hay hidroximetyl. Mch nhnh ti C17 c 2, 3,
5, 8, 9 hay 10 nguyn t Carbon, nu mch nhnh b loi, v tr 17
thng mang mt nhm chc oxi ha.
- Nhm OH c th gn ti Carbon s 3, 7, 11 hay 12.
- Nhm CO (carbonyl) thng thng gn ti Carbon 3
hay 11.
- Mt lin kt i c th hin din gia hai nguyn t
Carbon 4-5, 5-6 hoc 7-8. Sau cng, nhn A v i khi c
nhn A v B l nhn benzen, trng hp ny, nhm C10
metyl b loi.
29
28
21 22 24
20 25 26
18 23
12
11 17
19 27
13
1 16
2 9 14 15
10 8
3 5 7
4 6
Cu hnh ti C5 c biu th
- Nhm 5( (A/B trans) khi 2 vng A, B sc hp kiu trans.
- Nhm 5( (A/B cis) khi 2 vng A, B sc hp kiu cis.
R R
12
11 17 17
.
13 13
1 16
1
.
2 9 14
10 8 15 2
10
3 7 3
5
5
4 56 4 5
Cu hnh ca Steroid
5
2
3 4
Cu trng ca Stroid
6.3.3. Sterol
Cholesterol l thnh phn chnh trong sn mt ca
ngi, l nhn t gy ra bnh v tun hon, x cng ng
mch. Cholesterol tn ti di dng t do hay di dng
ester v c phn b rng trong c th, c bit trong m
thn kinh v no.
V mt lp th, Cholesterol c tm nguyn t Carbon bt i,
phn t gm nhn perhidrociclopentanophenantren vi C10CH3;
C13CH3; C17nhm ankyl c tm nguyn t Carbon, OH ti C3
c cu hnh (, mt ni i ti C5 v C6. S hidro ha ni i to
ra hai nguyn t C bt i mi v hai ng phn. S hidro ha t
pha trn dn n 5(H vi s dung hp A/B cis to nn sn phm
Coprostanol, ngc li s hidro ha t pha di s cho
Colestanol (5(H vi s dung hp A/B trans).
H3C
3
11
3
2
12
10
9
4
7
6
1
8
5
13
16
14
15
17
18
19
H
C
O
CH3 R
13
11 17
CH3 12
15
14 16
2 8
1 10
9 7
HO 4
25
26
24
23
22
27
5 6
3 2
+H2 +H2 1
0
CH3
R
CH3
CH3
1 R
H 11 13
12
6 CH3 17
5
2 2 10 9
1 8 15 16
14
3 4 HO
HO 4 6
3 5 7
R C8H17
H
COLESTEROL
(t pha () (t pha ()
( )
COPROSTANOL COLESTANOL
( )
Mc d, Colesterol khng tn ti trong thc vt, nhng ngi
ta thy trong cy nhng sterol tng t gi l Phytosterol, cht
quan trng nht trong loi ny gi l Ergosterol, di tc
dng ca tia t ngoi, ergosterol cho vitamin D2 (chng bnh
ci xng, ging vitamin D) l yu t chnh trong s tng trng
bnh thng ca xng v rng ca ng vt.
6.3.4. Acid mt
Acid mt cng c sn cn bn nh sterol, phn t c cha
OH ti C3, C7 v C12, nhm OH ny nh hng ( vi A/B cis.
Acid mt phong ph nht l acid colic v acid desoxicolic (khng
c OH C7).
S phn gii cu trng gii thch ti sao s acetyl ha OH ti
C3 d hn ti C7 v C12. Nhm OH xch o d gim cp hn
nhm OH trc nn d b tn cng bi RCO. Ch c OH C3
trong acid colic l chim v tr xch o.
(a)
Acid
CH colicCH3
3
(a)
CH3
OH
1 (e)
COOH
H
7
2
OH
OH
6.3.5. Kch thch t phi tnh.
( Kch thch t n gi l Estrogen.
( Kch thch t nam gi l Androgen.
Estradiol l mt estrogen chnh v hai dn xut estron v
estriol u c hot tnh sinh l.
Progesteron cng l mt kch thch t n khc, c tit ra t
th vng ca non so, c chc nng hnh thnh v duy tr thai
nhi.
Testosteron v androsteron l nhng androgen chnh.
Testosteron c tit ra bi dch hon l mt kch thch t
nam. Androsteron c sn sinh t s chuyn ha ca
testosteron.
H3C O H3C OH
H H
H H H H
HO Estron HO Estradiol
CH3
H3C OH
H3C C O
H H3C
H
H H
Estriol Progesteron
CH3 CH3
CH3
O O
H CH3
H
HO H
O
Cu to lp th ca Estron Cu to lp th ca
Progesteron
H3C OH H3C O
H3C H
H H3C
H
H H H H
O HO
Testosteron Androsteron
H
Chng 7: HA LP TH NG
7.
7.1. Hiu ng lp th
7.1.1. Khi nim
7.1.2. Hiu ng khng gian loi 1
7.1.3. Hiu ng khng gian loi 2
7.1.4. Hiu ng k
7.1.5. Hiu ng cu trng
7.1.6. Hiu ng orto
7.1.7. Hiu ng qua nhn
7.1.8. Tnh cht c nh ca cu trng
_ Quy tc Ingold
_ Quy tc Barton
_ Quy tc cng endo
7.2. Ha hc lp th ca cc phn ng
7.2.1. Phn ng th vo Carbon no
7.2.2. Phn ng tch
7.2.3. Phn ng cng Electrophile
7.2.4. Phn ng cng Nucleophile
7.1. HIU NG LP TH
7.1.1. Khi nim
Hiu ng lp th l hiu ng do kch thc ln ca
cc nguyn t hay nhm nguyn t v do bin dng ca gc
ha tr hay ca cc lin kt to nn. Hiu ng lp th c
biu hin qua s cn tr khng gian, qua sc cng gc ha tr
hay lin kt lm nh hng n hng v tin trnh lp th
ca phn ng, n tnh cht v bn ca cc ng phn.
7.1.2. Hiu ng khng gian loi 1
L hiu ng gy ra bi cc nhm th c kch thc tng
i ln lm cn tr s tng tc ca tc nhn i vi tm phn
ng hoc lm thay i hiu s nng lng t do gia phn t v
trng thi chuyn tip.
_ nh hng n phn ng lng phn t c th do
tc nhn hoc cht nn.
_ nh hng n s hon thnh trng thi chuyn
tip, lm tng nng lng hot ha v do lm gim tc phn
ng.
Th d: so snh kh nng phn ng ca aceton v ca ditert-
butylceton vi dung dch bo ha NaHSO3
7.1.3. Hiu ng khng gian loi 2
L hiu ng gy ra bi cc nhm c kch thc ln vi
phm n tnh song song ca trc cc orbital p trong h lin
hp lm cho hiu ng lin hp mt tc dng, thay i tnh
cht ca phn t.
Th d: so snh kh nng phn ng ca N,N-dimetyl anilin v
ca 2,6-dimetyl-N,N-dimetyl anilin vi mui benzen diazonium
Th d: gii thch cc gi tr pKa ca:
Cht Phenol pnitrophenol 3,5dimetyl4nitrophenol
pKa 10,0 7,2 8,2
7.1.4. Hiu ng k
Hiu ng k xut hin khi phn t cht phn ng c mang
nhng nhm chc khc -Z vi nhng i electron t do v mt
v tr thch hp (thng cch tm phn ng 2, 3, 4 nguyn t)
Nhm -Z ny c kh nng tn cng vo tm phn ng trc
khi tc nhn Y tc dng, nh hng n cu hnh ca sn phm.
Z: ; ; ; ; ;
_ _ _ _ (-) _
;
__ _ _O __ _
O _ C CH3
NH2 _ OH
Th d: _ SH _ C _
Br O O H O O
NaOH loang
H H3 C
H3 C O O
Ion (R) bromopropionat (S) lacton
HO O
NaOH ac
H
H3 C O
Ion (R) lactat
CH3
CH3
H H - TsOH
H E2
H H
OTs
O
H3C S OH
O
TsOH l
H
O O
H
O
Anhidric maleic O Endo
Sn phm cng
O
7.1.6. Hiu ng orto
L hn hp ca cc hiu ng lp th loi 1, loi 2,
hiu ng cm, hiu ng trng, lin kt hidro (nu c).
Th d: Orto R C6H4 NH2 c tnh baz nh hn cc ng
phn meta, para R C6H4 NH2.
7.1.7. Hiu ng cu trng
Sc cng Baeyer gii thch km bn ca vng 3C,
4C v cc vng khc c cu trng thch hp trnh sc
cng Baeyer.
_ Sc cng Pitzer
_ Sc cng Prelog
_ Sc cng ca cc lin kt
Cc sc cng lp th ny to ra cc hiu ng cu trng
nh hng n bn v tnh cht ca phn t.
7.1.8. Hiu ng qua nhn
L hiu ng ca cc nhm c th gy nh hng hoc tc
dng trc tip xuyn qua nhn (vng ) do chng gn nhau.
OH
O
+ H2 Ni
O OH
7.2. HA HC LP TH CA PHN NG
7.2.1. Phn ng th (substitution)
7.2.1.1. Phn ng SN2
Phn ng SN2 xy ra vi s nghch chuyn cu hnh ca tm phn ng;
qua trng thi chuyn tip
C 2H5 - C 2H5
C 2H5 -
+ ddNaOH -Br HO
Br HO Br H
H SN2 CH3
H CH3
H3 C
(S) 2 brombutan (R) butan-2-ol
R1 Cl - HCl R1 t0 R1
_
O
_
OH + S O
R2
Cl
R2 S O R2
Cl
R3 R3 R3
Cl
Clorosulfit ankyl
Nu phn ng xy ra trong mi trng baz hu c (nh
piridin) th phn ng din ra theo c ch SN2.
R1 R1
_ + SOCl2 O
_ H
O
R2 (piridin) R2
- HCl S O
R3 R3 Cl
_
+ HCl* N
+ *Cl
N +
H
R1
R1
t0 _
_
_ O - SO2 *Cl + Cl
*Cl R2 S O
R2
R3 R3
Cl
7.2.1.4. Phn ng SN2 (c s di chuyn ni i)
Trong phn ng SN2 tc nhn Y(-) tn cng vo phn t
cng mt pha vi nhm b th X(-).
R R
SN2'
HH
+ X
+Y Y
Y X
(X, R : Trans) (Y, R : Trans)
7.2.1.5. Phn ng SE
S chuyn ha mt halogenur quang hot (C*X)
thnh mt hp cht c kim, thng dn n sn phm
racemic.
R1 R1
-X
* X + M * M
R2 R2
R3 (M : kim loi) R3
R1 R1
COOH + HOOC
R2 Hn hp (() R2
1) + CO2 R3 R3
2) + H2 O
R1 R1
H Hn hp (() H +
R2 R2
Ngi ta gii thch s Racemic
R3 trn SE nh sau: phn ngRSE
3
qua trung gian ion Carbanion tng t nh s nghch chuyn cu
hnh ca NH3 v amin.
R1
R2
M M
+
+
R1
. . R1
R2
R2
R3 R3 R3
7.2.1.6. Phn ng SR Ion Carbanion
V phn ng th SR qua trung gian gc t do m gc t do c
c cu phng, orbital cha mt electron c thn c trc i xng
vung gc vi mt phng trn. Nn tc nhn c th tn cng vo
tm phn ng t hai pha vi xc sut bng nhau cho ta hn hp
racemic.
ClCH 2
H 3C
H
+ Cl
(- HCl)
. CH 2Cl
+ Cl 2
C 2H 5 H 3C C 2H 5
ClCH 2 ClCH 2
Cl + Cl + 2Cl
H 3C CH 3
C 2H 5 hn hp (() 1,2 dicloroC22H5 metylbutan
Ph CH3 Ph
Br H
NaOH / EtOH,t0
E2
+ HBr
H CH3
H Ph Ph
treo trans
Tch X2 (halogen)
_ ng phn treo cho anken cis
_ ng phn eritro cho anken trans
Br
H CH3 H CH3
E2 + Br2
H3C H (Aceton) H
H3C
Br
H CH3 H
Br H3C
E2 + Br2
Br (Aceton) CH3
H3C H H
eritro trans
2,3 dibromobutan but-2-en
H3C H CH3
Br H3C
E2 + Br2
Br (Aceton) H
H3C H H
treo cis
H3C CH3
H3C CH3 H
H
H3C Cl mentyl
clorur Cl
H3C
CH3 + HCl
H3C2 menten (100%)
Ngoi l:
Theo quy tc Bredt, khng th to ni i ti u cu
ca hp cht vng cu (kiu hon).
Br
X Khng tn ti
1 bromo-biciclo [2,2,1] heptan
Vi cu trc rn chc ca hp cht vng cu, th s quay
quanh lin kt C( C( khng tin hnh c, nn phn ng
tch E xy ra th phi c s chn lc gia tnh phng v tnh trans
ca hai nhm b tch. Thc nghim cho thy tnh phng u tin
hn, lc hai nhm b tch v tr cis.
Th d:
Cl -HCl H
HH (d dng)
Cl
kh (-HCl)
Cl
trans 2,3 dicloronorbornan
Cl
H Cl
H
cis 2,3 dicloronorbornan
7.2.2.2. Phn ng tch Ei
Phn ng tch Ei qua mt trng thi chuyn tip vng gm 5
hay 6 nguyn t, trong hai nhm b tch v tr cis i vi
nhau. Trng thi chuyn tip c cu trng che khut v cc nhm
trong cu trng s v tr cis trong anken hnh thnh.
R3
R3 A
R1
E2 R1
R4 + HB C
A R4
R2 z
H B A l : O, N, S R2
z B l : O hay S
Z l : R ; Ar ; SR ; OR ; NHPh ; Cl
Th d1:
H3C CH3
H3C H3C
CH3
H3C t0 CH3 +
O H3C
H
Ei
S H H3C
CH3S Ment-3-en ment-2-en
Metylxantat neomentyl (70%) (30%)
H3C
SCH3 CH3
S H3C
O
t0 Ment-3-en(20%)
H3C CH3
Ei
+ H3C S C SH
H H3C O
CH3
H3C H
Metylxantat mentyl H3C
Ment-2-en(80%)
Br
H CH3
C2H5
C2H5 H3C C2H5 H
H3C _ _ Br
+ Br2 - Br +
+ Br
H H
H Br Br H C2H5
cis
H
hn
H hpCH
(() treo
Br
3
Br
H CH3
H
C2H5 H C2H5 C2H5
H _ _ Br
+ Br2 - Br +
+ Br
H3C H C2H5
H Br Br H
H3C trans
eritro
H ()3 Br
CH
Br
C2H5 H C2H5 H
+ Br2
H CH3 H CH3
Trans pent-2-en
Br
eritro ()
2,3 dibromopentan
b) Cng HX (HCl, HBr, HI, HO Cl)
u theo c ch AE, kiu trans.
AE Br
H3C
+ HBr
H
H3C CH3 HC 3
H3C CH3
Ni
H3C C C CH3 + H2
t0 H
C C
H
CH3
Ni
+ H2
t0
H3C
H
H3C CH3
H
cis 1,2 dimetylciclohexen cis (ea)
1,2 dimetylciclohexan
b) Hidroxil ha
S hidroxil ha ni i C=C bng dd KMnO4 hay OsO4
din ra theo hng cng cis phn ng qua trung gian Ester vng.
Na2 SO 3
+ KMnO4
O O H2 O
H H Mn
O O
cis ciclopentan-1,2-diol
HO OH
S hidroxil ha bng peracid: phn ng tin hnh qua Eter
vng, sn phm hnh thnh theo kiu trans.
H O
H H H
+ CHCO
3 3H
+ CH3 COOH
C 2H5 H 3C C2 H 5
H 3C
cis pent-2-en _
H
O OH (dd)
3 N
HC H S2
__ treo __ 2
H
H
HC 5
O
7.2.4. Phn ng cng Nucleophile AN
i vi hp cht carbonyl c C* bt i xng
khi ()
phn ng AN cho hn hp hai ng phn bn i quang vi t l
khc nhau, sn phm chng theo ng hng quy tc Cram: phn
t cht carbonyl c sp xp sao cho nhm >C=O
nm trong nh din (Tb, L* C ( , N) v tc nhn thn hch Y tn
cng vo tm phn ng t pha nhm c kch thc nh hn (N).
R
L L
L _ R
R Y Y
+Y
Tb Tb N Tb N
N
O _O _O
(sn phm chnh) (sn phm ph)
L, Tb, N: k hiu cc nhm c kch thc ln lt l ln,
trung bnh, nh.
PHN B
BI TP
NG PHN QUANG HC
Cu 1: Gi tn theo danh php (R,S) ca cc hp cht sau:
CH2OH CHO C2H5 COOH
H CH3 H3C CH(CH3)2 Br CH3 H3C NH2
Br H C2H5 CH3 H CH2Cl H CH2-CH3
C2H5 CH(CH3)2 CH C(CH3)3
CH
(A) (B) (C) 2 (D)
CH2OH COOH CHO COOC2H5
H Cl H OH H OH H NH2
H Cl H OH HO H H3C H
Cl H H OH H OH H3C C2H5
CH3 COOH CH2OH CH=CH2
(E) (F) (G) (H)
H OH C2H5 NH2 H OH
H COOH C(CH3)3
(A1) (A2) (A3)
NH2 CH3
H CH3 Cl
CH3 H3C OH CH2Br
(B1)
COOH H COOH
H OH H3C H CH2OH
C(CH3)3
(B2) (B3)
CH3
Cl CH3
H
CH2Br
CH3 CH2OH
(T1) (T2)
Br CH3
CH2OH OHC
C2H5 H
H Br CH3
(T3) (T4)
H COOH CHO
H3C H Ph
(E3) (E4)
COOH H COOH
CH3
H3C H C2H5 NH2
C2H5
H NH2 C2H5 H H2N H
C2H5 COOH H3C
(E5) (E6) (E7)
Cu 4: Cho cc ng phn sau y ca:
1 Bromo 3 metylpentan-2-ol
H OH H CH3
CH2Br CH3
H CH3 H OH
BrH2C H H OH HO H
C2H5 C2H5 C2H5
(X4) (X5) (X6)
Hy chiu cc cng thc trn sang cng thc chiu Fischer v cho
bit tng quan lp th gia:
(X1) v (X2) ; (X1) v (X3) ; (X1) v (X6).
(X4) v (X5) ; (X1) v (X4) ; (X2) v (X6).
Cu 5: Tng t cu (4) vi cc ng phn sau y:
COOC2H5 H Ph
H CH3 NH2
H2N H CH3
Ph H COOC2H5
(T1) (T2)
COOC2H5 COOC2H5
H3C H H Ph
H NH2 H2N H
Ph CH3
(T3) (T4)
Cho bit tng quan lp th gia:
(T1) v (T2) ; (X1) v (T3) ; (T2) v (T4).
Cu 6: Dng cng thc chiu Newman hy biu din cc hp
cht sau:
Cl (chiu
Cl ng thi theo cc trc chCH
H3C nh)
3
(A) (B)
Cu 7: Gi tn y hai hp cht sau y:
Cl Cl
H3C NO2 Br
CH3
(X) Cl (Y)
CH3 CH3
(D) (E) (F)
Cau 26: Xt cu hnh v tnh bn tng i ca:
a) Cis v transdecalin.
b) Cis v trans 9metyldecalin.
c) Cis v trans 9,10dimetyldecalin.
d) Cis v trans 1,3dimetyldecalin.
Cau 27:
a) Dng cng thc chiu Newman biu din cc ng
phn ca 9,10dihidroxidecalin. Cho bit cu trng no u i
nht? Gii thch.
b) Tng t cu hi trn, vi hp cht:
Ciclohexan-1,2-diol.
Ciclohexan-1,3-diol.
Cau 28: Dng cng thc chiu Newman biu din cc ng
phn ca nhng phn t sau y theo nhng trc ch
nh:
a)
CH2
b)
CH3
C CH3
O
c)
C CH3
O
d)
H3C C C CH3
C C
O O
C C
b) O O
c)
(ch chiu theo phi cnh)
PHN NG TH SN
OH Alcol + Olefin
b) (R) - 1 - phenyletanol Clorur ankyl
Acetat quang hoat Alcol quang hoat
Tosilat Iodur (R) - 1 - phenyletyl
Cau 36: Gi s s thy gii Clorur ciscrotil bng nhng phn
ng ring bit theo:
- C ch SN1.
- C ch SN2.
Trong mi trng hp, hy cho bit alcol crotil to thnh l
ng phn cis hay trans, hoc mt hn hp hai dng trn. Gii
thch.
Cau 37: D on sn phm to thnh trong phn ng ca SOCl2
vi:
a) R1phenyletanol.
b) OH
CH3
CH2Cl
CH3
Ph C O C X
CH3 O
O C CH3 O CH3
c) + H3 C - COONa
O C
OTs (EtOH) O CH3
Cl Cl
C C + 2I C C + I2 + 2 Br
Br Br
Cl
(A) H (B) (C)
Cau 46: Tin on sn phm chnh trong phn ng kh sau y
a)
CH3
H3 C CH2 CH C CH2 CH3 + NaOH t0
ac
CH3 Br
CH2OH
b) H2SO4
CH3
t0
H3C OH
+ _
c) H3C CH2 CH N (CH3)3OH t0
CH3
d) (CH 3)3COK
Br t0
CH3 Br CH3
+ Br2 C2H5ONa
Ph CBr CHBr Ph Ph C C Ph
Br
Cau 48: Xt cc ng phn cu trng ca diclorostilben
a) Biu din ba cu trng ng ch ca dng meso v
ca dng treo bng cng thc chiu Newman.
b) Momen lng cc ca dng meso ((=1,27D) nh hn
momen lng cc ca dng treo ((=2,75D). Gii thch.
c) Cho bit sn phm kh HCl ca hai dng trn.
Cau 49:
a) Tc dng ca C2H5ONa trn Eritro3,4dimetyl3
bromohexan quang hat trong mi trng C2H5OH a n mt
hn hp sn phm lm quay mt phng nh sng phn cc, trong
c bn cht (cha lin kt i C=C v cha eter).
Vit c cu cc sn phm phn ng v gii thch c ch.
b) Tc dng ca C2H5ONa trn Treo2bromo3
metylpentan quang hat trong C2H5OH cng cho mt hn hp
lm quay mt phng nh sng phn cc, hn hp ny ch cha hai
cht (c ni i C=C v cha eter).
Cho bit ha hc lp th ca cc sn phm phn ng.
Cau 50:
a) Kho st s cng brom vo trans v cisstilben. Vit
cng thc chiu Newman ca cc sn phm to thnh.
b) S tch HBr trong dibromur stilben bng dung dch
baz l phn ng bc hai.
Cho bit sn phm to thnh vi mi ng phn lp th
nguyn thy (dng cng thc chiu Newman gii thch).
c) Nu mt nhm CH3 thay th mt nhm phenyl trong
dibromur stilben, phn ng tch HBr xy ra nh th no?
d) Trong mi trng hp trn, sn phm no to thnh
nhanh nht?
PHN NG CNG
OMe
a) Tc dng vi HOCl, sau x phng ha phm vt
to thnh. Cho bit c cu ca hp cht (B) nhn c.
b) un (B) trong mi trng acid. Hp cht (C) to thnh
c tnh quang hot khng? Vit c ch phn ng.
c) Cho (C) tc dng vi LiAlH4, sau un trong mi
trng acid. Cho bit c cu hp cht (D) to thnh. (D) c hon
ton ging (A) khng?
Cau 56: nhit thng, 1,2dimetilenciclobutan cng mt
phn t anhidric maleic cho hp cht A (3 vng)
C10H10O3. 1500C, A ng phn ha thnh B (2
vng) v phn ng cng mt phn t anhidric maleic th
hai vo B thnh cht C (4 vng) C14H12O6. Xc nh
c cu ca A, B, C.
Cau 57: Xt phn ng ca CH3OH vo 1,2epoxypropan vi s
c mt ca:
a) CH3ONa.
b) H2SO4.
Cho bit c ch phn ng v c cu nhng sn phm to
thnh trong mi trng hp.
Cau 58: S kh (R) 3phenylbutan-2-on quang hot (A) bng
LiAlH4 cho hn hp hai ng phn (B) v (C) vi t l
5:2.
a) Xc nh c cu ca (B), (C) v gii thch ha hc lp
th ca phn ng.
b) Kho st s dung mi gii dn xut Tosilat ca hai
alcol (B) v (C) trong CH3COOH. Cho bit c cu cc sn phm
v ha hc lp th ca phn ng.
Cau 59: Mt aldehid quang hot A (C9H10O) tc dng vi
CH3MgBr cho hai cht bn i quang B v C
(C10H14O) (B nhiu hn C). Cc bromur dn xut t B
v C (C10H13Br) ln lt tc dng vi KOH trong alcol
nhit cao cho hai alken ng phn D v E
(C10H12). S ozon gii D cho acetophenon v aldehid
acetic.
Dng cng thc chiu Newman biu din cng thc cc hp
cht A, B, C v gii thch cc phn ng xy ra.