stereokimia

Stereokimia mengacu pada sifat 3-dimensi dan reaksi dari

molekul. Masalah stereokimia memiliki bahasa dan
istilah khusus yang digunakan sebagai hasil kesepakatan
untuk berkomunikasi para ahli stereokimia.
 Definitions
• Stereoisomers – senyawa dengan konektivitas yang sama,
pengaturan yang berbeda dalam ruang

• Enantiomers – stereoisomers that are non- superimposible

mirror images; only properties that differ are direction (+ or
-) of optical rotationstereoisomer yang non gambar cermin
superimposibel; hanya properti yang berbeda adalah arah (+
atau -) rotasi optik
• Diastereomers – stereoisomers that are not mirror images;
different compounds with different physical properties
• stereoisomer yang tidak gambar cermin; senyawa yang
berbeda dengan sifat fisik yang berbeda
• Stereoisomers: Same molecular formulae, same connectivity;
same constitutional isomer. Different spatial orientation of the
bonds.
rumus molekul yang sama, konektivitas yang sama; isomer
konstitusional yang sama. orientasi spasial yang berbeda dari
obligasi.

Two kinds of Stereoisomers

– Enantiomers: stereoisomers which are mirror objects of each other.
Enantiomers are different objects, not superimposable. stereoisomer
yang benda cermin satu sama lain. Enantiomer adalah objek yang
berbeda, tidak superimposibel
– Diastereomers: stereoisomers which are not mirror objects of each
other. : Stereoisomer yang tidak mencerminkan objek satu sama lain.
 More Definitions
• Asymmetric center – sp3 carbon with 4 different
groups attached
• Optical activity – the ability to rotate the plane of
plane –polarized light
• Chiral compound – a compound that is optically
active (achiral compound will not rotate light)
• Polarimeter – device that measures the optical
rotation of the chiral compound
ISOMER GEOMETRI PADA ALKENA

ALKENA: RIGID

C2H4
Isomer geometri cis & trans
Isomer geometri E & Z.

6
Alkena

Isomer Cis-trans    diastereomers .

Alkena

Cl Cl H Cl
C C C C
H H Cl H
cis-dikloroetillena trans-dikloroetilena
Sisi yg sama Sisi berlawanan

Perhatikan posisi relatif dari kelompok yang lebih

besar pada tiap atom karbon dalam ikatan ganda.
ISOMERI GEOMETIK DALAM SENYAWA SIKLIK
 Isomer cis & trans

H H

H trans-1,2-dimetilsikloheksana
H paling stabil e-e karena :
H H - gugus meruah stabil pada posisi e
- jarak antar gugus paling jauh sehingga gaya tolak minimum
H
H3C H
CH3

H H

H H

H H
H cis-1,3-dimetilsikloheksana
H paling stabil e-e karena :
- gugus meruah stabil pada posisi e
- jarak antar gugus paling jauh sehingga gaya tolak minimum
H
H3C CH3
H

H H

10
 Isomer cis & trans

H H

H trans-1,2-dimetilsikloheksana
H paling stabil e-e karena :
H H - gugus meruah stabil pada posisi e
- jarak antar gugus paling jauh sehingga gaya tolak minimum
H
H3C H
CH3

H H

H H

H H
H cis-1,3-dimetilsikloheksana
H paling stabil e-e karena :
- gugus meruah stabil pada posisi e
- jarak antar gugus paling jauh sehingga gaya tolak minimum
H
H3C CH3
H

H H

11
Enantiomer 2-butanol

CH3 H3C

C2H5 C C2H5
OH HO
H H

bidang cermin

13
 Enantiomer R & S

CH3 2 3
C2H5 CH3
C2H5 C (R)-2-butanol
OH
H
OH
1
putaran searah jarum jam

H3C 3 2
H3C C2H5
C2H5 (S)-2-butanol
HO
H
OH
1
putaran berlawanan arah jarum jam
 Enantiomer (d) & (l)
• Ditentukan berdasarkan posisi OH pada atom C
kedua gliseraldehid berdasarkan proyeksi Fischer.
• Jika OH berada disebelah kanan maka disebut
enantiomer dextro (d).
• Jika OH berada disebelah kiri maka disebut
enantiomer laevus (l).
• Struktur senyawa dengan lebih dari satu pusat kiral
tetapi strukturnya tidak kiral disebut senyawa meso

15
 CO2H CO2H
H
H
O O O HO
H H
OH HO
CH CH COH OH
CO2H
CO2H
H C OH H C OH H C OH l-(-)-asam tartrat d-(+)-asam tartrat

HOH2C CH2OH CH2OH

(d) gliseraldehida (d) asam gliserat asam rasemat
[]D20 = + 8,7 []D20 = - CO2H

O OH
O O
H H

CH COH HO CO2H
CH
CO2H CO2H
HO C H HO C H HO C H
H
CH2OH H OH
HOH2C CH2OH
CO2H HO
(l) gliseraldehida (l) asam gliserat
[]D20 = - 8,7 []D20 = + HO
H
H
OH
CO2H
asam meso tartrat
 Stereochemistry
Stereochemistry refers to the
3-dimensional properties and
reactions of molecules. It has its
own language and terms that need
to be learned in order to fully
communicate and understand the
concepts.
 Latihan soal stereokimia
• Manakah dari senyawa dibawah ini yang dapat
membentuk isomer geometri?Jelaskan
– CH3CH=CBr2
– CH3-CBr=CBr-CH3
– CH3-CH2-CH2-CH=CH-CH3
•Susunlah urutan prioritas dari:
•-H, -Br,-CH2CH3,-CH2-CH2OH
•-CN,-CH3NH2,-CH2NHCH3,-NH2
•-Br,-CH(OH)CH3,-CH3,-H
 Latihan
• Gambarkan konfomer dari 2 butanol
• Dari senyawa berikut, mana yang mempunyai pusat
kiral ?
– 1-kloro butana
– 3-kloro-2-butanol
– 4-bromo-1-klorosikloheksena
– 1,3-dimetil benzena
• Gambarkan isomer R & S dari :
– 3-fenil-2-butanol
– Asam 2-amino-3-hidroksibutanoat
19
• Tentukan konfigurasi absolut,R,S untuk ketiga
senyawa optis aktif berikut ini lengkap dengan
nama
CH 3

H COOH
Br
• Tulislah konfigurasi R atau S untuk setiap atom
karbon asimetris pada senyawa-senyawa
dibawah ini, dan tentukan pula pasangan2
senyawa yang berbentuk enansiomer atau
deastereomer
Br Br Br H

H CH 3 H3 H H CH 3 Br CH 3
C
H OH H3 H H CH 3 H3 H
C C
CH 3 OH OH
OH
• Gambarkan proyeksi ruang (a)Newman dan (b)Fisher
untuk enansiomer dari
2-klorobutana, H3C-CHCl-CH2-CH3
• Gambarkan proyeksi Newman bentuk eclipsed dan
staggered dari propana, H3C-CH2-CH3
• Tuliskan struktur molekul senyawa –senyawa yang optis
aktif dengan rumus molekul seperti dibawah ini
– C5H10O2
– C5H12O
• Berapa banyak stereoisomer yang mungkin terjadi pada
senyawa berikut?
– Metilsiklopropana
– Metilsiklobutana
– 1,2dimetilsiklopropana
Plane-Polarized Light
Plane-Polarized Light through an Achiral
Compound
Plane-Polarized Light through a Chiral
Compound
Polarimeter Measures
Optical Rotation
Optical Activity
 Specific Rotation, [α]

[α] = α / cl
a = observed rotation
c = concentration in g/mL
l = length of tube in dm

Dextrorotary designated as d or (+), clockwise

rotation
Levorotary designated as l or (-), counter-
clockwise rotation
Specific Rotations of some Common Organic
Compounds

Compound [a] # * centers

Penicillin V +233.0 3
Sucrose +66.5 10 
Camphor +44.3 2
MSG +25.5 1
Cholesterol -31.3 8
Morphine -132.0 5
 Chirality Center
Carbon has four different groups attached
 Enantiomers
nonsuperimposible mirror images
mirror
plane
OH OH

H CH3 CH3 H
HO 2C CO2H

(S)(+) lactic acid (R)(-) lactic acid

from muscle tissue
o
from milko
[] = +13.5 [] = -13.5
 Enantiomeric Excess
(Optical Purity)

observed rotation
rotation of pure enantiomer x 100 = enantiomeric excess (e.e.)
o
observed rotation = +109
109.0
e.e. = 123.0 x 100

= 88.6% e.e.
H H
88.6% (+)
(S)-(-) Limonene (R)(+) Limonene 11.4% racemic
o o
[=  [] = +123.0 actually 94.3% (+)
from lemons from oranges
Biological Activity
SSRI Efficacy depends on Stereochemistry
Naming of configurations.

S R
Absolute Configuration
Assign Priority to each Group on
Asymmetric Center
Lactic Acid
C.I.P. Priorities
Low High
CH2CH2CH3 CH(CH3)2
O
CH2CH2OH CH2CH

CH2CH2CH3 CH=CH2

CO2H CH2Cl

CH2CH2Br CH(CH3)2
 Fischer Projections

OH OH OH
H CO2H H CO2H
H CH3
HO2C CH3 CH3

Horizontal bonds approach you (wedge bonds)

Vertical bonds move away (dashed bonds)
 Assigning Absolute Configuration to
Fischer Projections

OH OH OH
H CO2H H CO2H
H CH3
HO2C CH3 CH3
rotate
(S) (S) (S)
 Rotation of the Projection 90o
Reverses Absolute Configuration

OH o H CH3 o
90 o
90 CO2H
90
H CO2H CH3 OH HO2C H HO CH3
CH3 CO2H OH H
(S) (R) (S) (R)
 Diastereomers
Stereoisomers That Are Not Mirror Images

H OH H OH
3 3
2
2 CO2H CO2H
H Br Br H
(2S,3S) (2S,3R)
same stereochemistry at C2 (S)
opposite stereochemistry at C3
Fischer Projections with 2 Chiral Centers

CO2H CO2H
2 2
H OH H OH

3 3
Br H H Br

CH3 CH3
(2S,3S) (2S,3R)
2 Chiral Centers
4 Stereoisomers
Identical, Enantiomers or Diastereomers?
 Tartaric Acids
R,R S,S
CO2H CO2H

H OH HO H

HO H H OH

CO2H CO2H
R,S S,R
CO2H CO2H

H OH HO H

H OH HO H

CO2H CO2H
 Racemic Mixture
R,R S,S
CO2H CO2H

H OH HO H

HO H H OH

CO2H CO2H
Racemic Mixture (Racemate): 50/50 mixture of enantiomers

(R,R) Tartaric acid (S,S) Tartaric Acid (+/-) Tartaric acid

o
m.p. C 168-170 168-170 210-212
[] (degrees) - 12 + 12 0
(g/mL) 1.7598 1.7598 1.7723
 Meso Compound
Internal Plane of Symmetry
Optically Inactive

R,S S,R
CO2H CO2H

H OH HO H
mirror
plane
H OH HO H

CO2H CO2H
o
rotate 180
superimposible
 2,3,4-trichlorohexane
How many stereoisomers?

Cl

* * *
Cl Cl
3 asymmetric centers
2n, n= # asymmetric centers (3)
8 stereoisomers
 n = 3; 2 = 8 n

CH3 CH3 CH3 CH3

S H Cl Cl H R H Cl Cl H
S H Cl Cl H R H Cl Cl H
RH Cl Cl H S Cl H H Cl
CH2CH3 CH2CH3 CH2CH3 CH2CH3

CH3 CH3 CH3 CH3

H Cl Cl H Cl H H Cl
Cl H H Cl H Cl Cl H
H Cl Cl H H Cl Cl H
CH2CH3 CH2CH3 CH2CH3 CH2CH3
A Carbohydrate
CHO
H OH R

HO H S

H OH R
H OH R
CH2OH
(+) D-Glucose
Internal Planes of Symmetry

Both are Meso

CH3 CH3 CH3 CH3

CH3 CH3 CH3 CH3

Asymmetric Centers on Rings

Br Br
Br Br
Br Br

A B
1(R),2(S) cis 1,2-dibromocyclohexane
nonsuperimposible but A flips into B Meso
 Allenes can be Chiral

H H
H H
C C C C C C
Cl Cl
CH3 CH3
 Mycomycin, an antibiotic

H
H
C C C
H C C C C
CH=CHCH=CHCH2CO2H
o
Nocardia acidophilus []D = -130
 Reactions that Generate Chirality Centers
Hydrogenation, syn

CH3 CH3 H H
H2, Pt/C
CH3 CH3
CH2CH3 CH2CH3 CH2CH3 CH2CH3

CH2CH3 product is meso

H CH3
H CH3
CH2CH3
 Bromination
Trans is formed exclusively
No Meso is formed (cis)

Br2

Br Br Br Br
R R S S
racemic mixture
Bromonium Ion is Opened Equally from
Both Sides

Br2

-
+  Br Br Br Br
Br Br R R S S
racemic mixture

Br Br

Br Br
 trans alkene + anti addition = MESO

CH2CH3 H Br2 CH2CH3 Br

H
H
H CH2CH3 Br CH2CH3

CH2CH3 CH2CH3
H H
meso
Br Br
 cis Alkene + anti addition =
racemic mixture

Br
CH2CH3 CH2CH3
H H
a Br b
CH2CH3 Br Br CH2CH3
CH2CH3 CH2CH3 H H
Br2
CH2CH3 CH2CH3
H H Br H H Br
a b

CH2CH3 HCH CH H CH2CH3

H 2 3 CH CH
2 3 H
R R S S
Br Br Br Br
 Brominations Often Generate Asymmetric
Centers

CH3 CH3 Br2 CH3 CH3 CH3 CH3

H H H H
H H Br Br Br Br
S S R R
racemic mixture

CH3 CH3 Br CH3 CH3

H Br2 H
H H H
H CH3 Br CH3 Br Br
S R
meso
Asymmetric Center is Generated
Racemic Mixture Formed
Br
H-Br H
H

a) (R) Br b) (S)
a)
H Br
H

Br b)
 Asymmetric Induction

PPh2
RuCl2
PPh2

CH3 H CH3
H2
OH OH
Ru(BINAP)Cl2
96% e.e.

Noyori and Knowles shared Nobel Prize in Chemistry, 2001

 Preparation of (L)-Dopa
for Treatment of Parkinson’s
HO

HO NH2
C=C
H CO2H
H2
Rh(DIOP)Cl2

CO2H
HO CH2C enz. HO CH2CH2NH2
H
NH2
HO HO
l-(-) Dopa Dopamine
cannot cross blood-brain
barrier
 Relevance of Stereochemistry

EPHEDRAfrom Ma Huong
OH
NHCH3 d-pseudoephedrine and l-ephedrine
* * (R,S) (S,S)
CH3 useful decongenstants

2 asymmetric centers
4 stereoisomers
 One-step synthesis

Pseudophed

NHCH3 "desoxyephedrine"
*
(methamphetamine)
CH3 l-(R) - Vicks
d-(S)- "Meth"
a-(p-isobutylphenyl)propionic acid

H H CH3
CH3 CO 2H HO 2C
(S)(+) ibuprofen (R)(-) ibuprofen
anti-inflammatory 80-90% metabolized to (S)(+)
Model of Thalidomide
 How Sweet it is!

OH Cl
CH2OH CH2OH
O O
CH2OH HO CH2Cl
HO O
O OH
OH
O HO O HO
CH2OH CH2Cl
HO HO
Sucrose Sucralose or Splenda

Sucralose is 600 times sweeter and does not

get metabolized.
Sildenafil (Viagra) and Caffeine
CH3 CH3
O N N O N

H N CH3 N N

CH3CH2O N N
O CH3

O
S
O
N

N
CH3
 Radiosensitizer of Choice Until 2004

OH
H
HOOC O O
O O O
OH H
O O
OH H H
OH

Okadaic acid
17 asymmetric centers