84
STEREOCHEMISTRY
of cyclopropane-1,2-dicarboxylic acid similarly do not
interconvert; interconversion would require the breaking
of bonds.
H
H 3 C
CH 3
H
H
H 3 C
H
CH 3
HO 2 C
H
CO 2 H
H
HO 2 C
H
H
CO 2 H
cis
cis
trans
trans
but-2-ene
cyclopropane-1,2dicarboxylic acid
The terms cis and trans are used to describe the
configuration, which is considered to be the spatial
sequence about the double bond or the spatial sequence
relative to a ring system. The cis isomer has substituents
on the same side of the double bond or ring system
(Latin: cis = on this side), whereas the trans isomer has
substituents on opposite sides (Latin: trans = across).
With simple compounds, like the isomers of but-2ene, the descriptors cis and trans are quite satisfactory,
but a compound such as 3-methylpent-2-ene causes
problems. Do we call the isomer below cis because the
methyls are on the same side, or trans because the main
chain goes across the bond?
H
H 3 C
CH 3
CH 2 CH 3
is this cis or trans?
3-methylpent-2-ene
For double bonds, the configuration is now usually
described via the non-ambiguous E,Z nomenclature,
assigned using the Cahn–Ingold–Prelog priority rules
for substituents on each carbon. First, consider each
carbon of the double bond separately, and assign
priorities to its two substituents. Then consider the
double bond with its four substituents. If the two
substituents of higher priority are on the same side
of the double bond, the configuration is Z (German:
zusammen = together), whereas if they are on opposite
sides, the configuration is E (German: entgegen =
across).
Thus, for the 3-methylpent-2-ene isomer we can see
that, for C-2, the substituents are methyl and hydrogen
with priorities methyl > hydrogen. For C-3, we have
substituents methyl and ethyl, with ethyl having the
Z
E
priority 1
priority 2
priority 1
priority 1
priority 2
priority 2
priority 1
priority 2
(E)-3-methylpent-2-ene
H
H 3 C
CH 3
CH 2 CH 3
priority 1
priority 2
priority 1
priority 2
(Z)-3-methylpent-2-ene
H
H 3 C
CH 2 CH 3
CH 3
priority 1
priority 2
priority 2
priority 1
2
3
2
3
higher priority. Thus, the high-priority groups are on
opposite sides of the double bond, and this isomer has
the E configuration. The alternative arrangement with
high-priority substituents on the same side of the double
bond has the Z configuration.
Box 3.9
Configurations of tamoxifen, clomifene and
triprolidine
The oestrogen-receptor antagonist tamoxifen is used
in the treatment of breast cancer, and is highly
successful. Clomifene is also an oestrogen-receptor
antagonist, but is principally used as a fertility drug,
interfering with feedback mechanisms and leading
to ova release, though this often leads to multiple
pregnancies.
O
NMe 2
tamoxifen
priority 1
priority 2
priority 1
priority 2
configuration (Z)
STEREOCHEMISTRY
of cyclopropane-1,2-dicarboxylic acid similarly do not
interconvert; interconversion would require the breaking
of bonds.
H
H 3 C
CH 3
H
H
H 3 C
H
CH 3
HO 2 C
H
CO 2 H
H
HO 2 C
H
H
CO 2 H
cis
cis
trans
trans
but-2-ene
cyclopropane-1,2dicarboxylic acid
The terms cis and trans are used to describe the
configuration, which is considered to be the spatial
sequence about the double bond or the spatial sequence
relative to a ring system. The cis isomer has substituents
on the same side of the double bond or ring system
(Latin: cis = on this side), whereas the trans isomer has
substituents on opposite sides (Latin: trans = across).
With simple compounds, like the isomers of but-2ene, the descriptors cis and trans are quite satisfactory,
but a compound such as 3-methylpent-2-ene causes
problems. Do we call the isomer below cis because the
methyls are on the same side, or trans because the main
chain goes across the bond?
H
H 3 C
CH 3
CH 2 CH 3
is this cis or trans?
3-methylpent-2-ene
For double bonds, the configuration is now usually
described via the non-ambiguous E,Z nomenclature,
assigned using the Cahn–Ingold–Prelog priority rules
for substituents on each carbon. First, consider each
carbon of the double bond separately, and assign
priorities to its two substituents. Then consider the
double bond with its four substituents. If the two
substituents of higher priority are on the same side
of the double bond, the configuration is Z (German:
zusammen = together), whereas if they are on opposite
sides, the configuration is E (German: entgegen =
across).
Thus, for the 3-methylpent-2-ene isomer we can see
that, for C-2, the substituents are methyl and hydrogen
with priorities methyl > hydrogen. For C-3, we have
substituents methyl and ethyl, with ethyl having the
Z
E
priority 1
priority 2
priority 1
priority 1
priority 2
priority 2
priority 1
priority 2
(E)-3-methylpent-2-ene
H
H 3 C
CH 3
CH 2 CH 3
priority 1
priority 2
priority 1
priority 2
(Z)-3-methylpent-2-ene
H
H 3 C
CH 2 CH 3
CH 3
priority 1
priority 2
priority 2
priority 1
2
3
2
3
higher priority. Thus, the high-priority groups are on
opposite sides of the double bond, and this isomer has
the E configuration. The alternative arrangement with
high-priority substituents on the same side of the double
bond has the Z configuration.
Box 3.9
Configurations of tamoxifen, clomifene and
triprolidine
The oestrogen-receptor antagonist tamoxifen is used
in the treatment of breast cancer, and is highly
successful. Clomifene is also an oestrogen-receptor
antagonist, but is principally used as a fertility drug,
interfering with feedback mechanisms and leading
to ova release, though this often leads to multiple
pregnancies.
O
NMe 2
tamoxifen
priority 1
priority 2
priority 1
priority 2
configuration (Z)