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Stereochemistry:
Arrangement of
Atoms in Space;
Stereochemistry of
Addition Reactions
enantiomers
9/06/07 update
1
Isomers
Isomers - compounds with the
same molecular formula but
different structures
Stereoisomers different 3D
structures
cis-trans are one example
H OH
HO H
H3 C
HO2C
CO2H
CH3
(S)-(+)-lactic acid
(R)-(-)-lactic acid
enantiomers
can't
superimpose
rotate
180o
Cl
C C
H
Br
CH3
CH2CH3
mirror
planes of
symmetry
Br
H3C
CH2
HO
C
O
Cl
Cl H
Br
Br
H
H Cl
H
Br
H*
H
Br
Cl
* = center of symmetry in
geographical middle of the molecule
same
mirror
180
R3
chiral center
R4 C R
2
R1
most chiral molecules contain chiral centers
but a molecule can be chiral and not contain a chiral center
How about 2,3-hexadiene? chiral / achiralwhich??
CH3
C C
H
H
CH2CH3
Alsomolecule with
2 or more chiral
centers can be
achiral
9
CH3
1.
2.
3.
chiral
achiral
Impossible to describe
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
10
Br
CH3CH2
C
H
Br
CH3
CH3CH2
CH3
H
11
12
exptl
rotation
temp
[]T
wavelength of
light; usually
sodium D line,
= 589 nm
c*l
conc of
sample
in g/mL
14
R1 O
heroin: R1 = R2 =
O
O
N
CH3
R2 O
morphine, R1 = R2 = H
[] = -132o
H3 C
codeine: R1 = CH3,
R2 = H
15
NH
C6H5O
O
HO
cholesterol
[] = -31.5o
penicillin V
[] = +223o
CO2H
OH
HO
O
HO
HO
glucose
[] = +53o
O
O
OH
HO
CH2OH
OH
sucrose
[] = +66.4o
fructose
[] = -92o
16
N
H
I
I
HO
NH3
N
N
nicotine
OH
OH
adrenaline
CO2
thyroxine (T4)
H
limonene
(lemon oil)
17
N
N
O
(R)-thalidomide
(antidepressant)
H
N
N
H
O
(S)-thalidomide
(mutagenic and
antiabortive)
H3CO2C
CH3
O
H
H3C
H
CH3
O
H
CH3
CH2
19
*
CH
CH
CH2
OH
H2
H3C
Pt
HO-H2C
CH2 CH3
CH3
[ = -5.8o
CH2 CH3
OH
o
[27
=
+33.2
D
*
CH
*
CH
o
[27
=
+13.5
D
HBr
Br-H2C
*
CH
CH2 CH3
CH3
[ = +4.0o
1951, first X-ray experiments were performed to allow the determination of the
absolute configuration of a molecule
21
22
1 4
HO H
H3C
3
1
OH
H is
hidden
H3C
3
CO2H
2
(R)-(-)-lactic acid
CO2H
2
clockwise = R
H2N
HO2C
CH3
3
CH3
H2N
1
CO2H
2
L-alanine
2-aminopropanoic acid
counter-clockwise = S
See: http://www.vanderbilt.edu/AnS/Chemistry/Rizzo/chem220a/absolute.pdf
23
3
CH3
H3C
CH2 C
2
H4
1
CH2 OH
1
CH2OH
C
H3C
3
C2H5
2
HOH2C
tip
forward
slightly
H3C
C2H5
24
C
H
Br
CH3
= CH3CH2
CH3
H
*90 rotation -> inverts the configuration (R -> S and vice versa).
*Can be rotated 180 about an axis perpendicular to the paper
without altering the configuration.
*If the projection is rotated in a way that lifts some groups
out of the paper, the absolute configuration will be reversed.
See: http://www.chem.uic.edu/web1/OCOL-II/WIN/STEREO/F12.HTM
25
CH2 CH3
H3C
CH
CH3
OH CH3
2,3-dimethyl-3-pentanol
CH3
H3 C
C
HO
Et
i-Pr
i-Pr
CH3
Et
i-Pr
Et
OH
(R)
OH
CH3
Et
interchange
i-Pr and Et
i-Pr
R -> S
OH
(S)
26
CH3
rotate 90
HO H
H3C
=
CO2H
OH
H3C
(R)-(-)-lactic acid
CO2H
H (R)
OH
CO2H (S)
rotate 180o
H
HO2C
OH
H3C
CH3
OH (R)
CO2H
H
How can you determine the absolute configuration from a Fischer projection??
27
Cl
CO2H
CH3CH2
H 3C H
41
42
43
44
61
62
63
64
1.
2.
3.
454. 46
65
66
CH3
E
Z
R
S47
67
48
49
50
51
52
53
54
55
56
57
58
59
60
68
69
70
71
72
73
74
75
76
77
78
79
80
28
different 3D structure
H3C
H3C
CH2
O
Not
enantiomers
OH
CH3
R&S
2 or more chiral
centers
29
30
CHO
* OH
* H
* OH
* OH
HO
# of chiral centers = 4
total # of stereoisomers =
24 = 16
CH2OH
(+)-glucose
31
CO2H
H
HO
OH
CO2H
enantiomers
CO2H
(2R,3R)-(+)tartaric acid
HO
H
OH
CO2H
diastereomers
(2S,3S)-(-)tartaric acid
CO2H
H
OH
OH
CO2H
CO2H
H
OH
OH
CO2H
33
(gm/ml)
H2O
solubility
(gm/100 ml)
+12
1.760
139
168-170
-12
1.760
139
meso
146-8
1.660
125
(+-)
206
1.788
20.6
Stereoisomer
Mp
(oC)
(+)
168-170
(-)
(o)
pKa # 1
pKa # 2
(+) or (-)
2.98
4.34
meso
3.23
4.82
34
CO2H
2
H
OH
3
H
OH
4CH
3
CO2H
CO2H
HO
HO
HO
CH3
(2S,3S)
(2R,3R)
(liquid)
OH
H
CO2H
HO
H
CH3
H
OH
CH3
(2R,3S)
(2S,3R)
(solid)
35
OH
H
CO2H
CO2H
HO
H
CO2H
HO
OH
OH
HO
OH
CO2H
CO2H
CO2H
(2R,3R)
(2S,3S)
(2S,3R)
CO2H
(2R,3S)
identical
meso isomer
36
1.
2.
3.
S
Neither
R
OH
Br
H CH3
C
38
(+)
(+)
(+)
(-)
50% is (+)
40
H
C CH HC C
H3C
racemic amine
[] = 0o
CH3
NH2
NH2
R
CO2H
H
HO
H2O
OH (2R,3R)-(+)H
tartaric acid
(chiral acid)
CO2H
.................diastereomers.................
CO2
H
H3C
C CH
NH3
H
HO
OH
H
CO2H
CO2
H
+ HC C
CH3 H
HO
NH
3
..different solubilities..
OH
H
CO2H
41
CO2
H
H3 C
C CH
NH3
(S)
OH
HO
H
CO2H
(R,R)
CO2
H
+ HC C
CH3 H
HO
NH
OH
H
(R)
CO2H
(R,R)
R,R,R-diastereomer
remains in solution
K2CO3, H2O
(weak base)
42
NH3+ + CO3-2
NH2 + HCO3H
H
H3C
C CH
NH2
(S) [] = -52.7o,
bp 82-4o
HC C
CH3
NH2
(R) [] = +53.2o,
bp 82-4o
Why arent the []s exactly the same magnitudewhat should they be?
43
44
achiral
Br
Et
H
Br
C2H5
H
H
H
Br
Et
H
Br
Et
H
achiral
CH3
(R)
CH3
Et
H
CH3
Br
(S)
CH3
racemic
mixture
45
OH
HCl
Et
i-Pr
CH3
racemic mixture
(R)
Cl
Et
i-Pr
Et
i-Pr
Et
i-Pr
CH3
Cl-
CH3
+
Et
i-Pr
CH3
(R)
achiral
CH3
(S)
Cl
46
H
H3C
Cl
CH=CH2
HBr
H3 C
Cl
H3 C
Br
H
H3C
Cl
Br
CH3
H
47
C2H5 CH3
C
C
+ HCl
C2H5 CH3
*
*
*
*
*
48
CH3
CH3
H2
Pt/C
CH3 H
2
CH3
Pd/C
CH3
H 15%
CH3
H
H
1.
2.
3.
4.
Meso
Racemic mixture
Achiral
Mixture of diastereomers
49
1.
2.
3.
4.
CH3CO3H
H3C
O
Racemic mixture
Mixture of disastereomers
Meso
None of these apply
51
52
Hydroboration-Oxidation.syn-addition of HOH
Brominationanti-addition of Br-Br
53
Br2
Br
H
H
Br
1.
2.
3.
54
55
56
R = bronchodilator (albuterol)
S = antagonist
H2N
OH
O
H2N H
Bitter
H2N
OH
O
Asparagine
H NH2
Sweet
57
Me
Et N:
Pr
Me Et
N
Me
:N Et
Pr
Pr
rapid equilibration
O
with sulfur the rate of
inversion is slow....
enantiomers can be isolated
R1
R2
58
O
H3C