E/Z (cis/trans) isomerism Cahn-Inglod-Prelog Priority Rules examples explained drawings diagrams difference in physical & chemical properties working out isomers for given structural formula A level GCE AS A2 organic chemistry revision notes

PART 14 ORGANIC ISOMERISM and Stereochemistry Revision Notes

Part 14.2 Organic Stereoisomerism - Introduction, priority rules and E/Z isomerism

(E/Z isomerism was called cis-trans, geometric or geometrical isomerism)

Doc Brown's Chemistry Advanced Level Pre-University Chemistry Revision Study Notes for UK KS5 A/AS GCE level organic chemistry students US K12 grade 11 grade 12 organic chemistry

email doc brown - comments - query?

All my advanced A level organic chemistry notes

All my advanced A level isomerism and stereochemistry notes

Use your mobile phone or ipad etc. in 'landscape' mode

This is a BIG website, you need to take time to explore it [SEARCH BOX]

E/Z stereoisomerism is explained and examples of E/Z isomers fully described including how to name them and assign the E or Z prefix to the specific isomer name. Case studies are described covering the molecular structure of the E/Z isomers, how to name them and explaining any differences in physical and chemical properties. A few details of differences in physical and chemical properties are pointed out where it seems appropriate. Note for simple cases modern E = old trans isomers AND modern Z = old cis isomers. Cis and trans notation is still to be found in older textbooks and even some contemporary literature. Case studies are discussed concerning structure, naming, formation, properties and stereochemical consequences of E/Z stereoisomerism

Sub-index for this page on E/Z isomerism

14.2(a) Introduction to stereoisomerism

14.2(b) Configuration priority rules - isomer assignment rules

14.2(c) Introduction to E/Z Isomerism and applying assignment rules

14.2(d) E/Z isomers of some hydrocarbon alkenes and halogenated alkenes

14.2(e) Further case studies of E/Z stereoisomerism, BUT, now including discussing the similarities & difference in physical & chemical properties of the E/Z isomers (with sub-sub-index!)

Case studies of E/Z (geometric) isomerism:

2a.1 C₄H₈ * 2a.2 HOOC-CH=CH-COOH * 2a.3 ClCH=CHCl

2a.4 di-substituted cycloalkanes

2a.5 azo (-N=N-) and R₂C=N-X compounds * 2a.6 Dienes * 2a.7 Trans fats

2a.8 But-2-enoic acid and 2-methylbut-2-enoic acid

2a.9 Organic analogues of the anti-cancer drug cis-platin

2a.10 Cis/trans retinal - biochemistry of the eye * Definition of diastereoisomers

14.3 R/S (Optical) Isomerism (separate page)

TOP OF PAGE and sub-index

14.2(a) Stereoisomerism-Stereochemistry - Definition and Introduction

Stereoisomerism occurs when two or more molecules have identical molecular formula AND the same structural formula (i.e. the atoms are arranged in the same order), BUT differ in their 2D or 3D spatial arrangements of their bonds - which means different spatial arrangement of the atoms - even though they are bonded in the same order!

There are two main sub-divisions of stereoisomerism:

(a) E/Z isomerism (old names: cis/trans geometrical/geometric isomerism, in specific cases E = trans, Z = cis isomers)

(b) R/S optical isomerism (was called optical isomerism)

A 3rd section (c), looks at other stereochemical examples which do not readily fit into (a) or (b).

However, before these sections, you need to read to know about 'priority rules' to assign the correct nomenclature to any absolute 2D or 3D stereoisomer configuration.

Section 14.2 (b) Configuration priority rules (c) E/Z Isomerism Section 14.3 R/S Optical Isomerism (separate page)

TOP OF PAGE and sub-index

14.2(b) Priority Rules for designating the precise isomer configuration in stereoisomerism

In order to specify exactly which stereoisomer you are referring to in e.g. E/Z (geometrical/geometric isomerism) and R/S optical isomerism (molecules exhibiting chirality) you need rules to account for the different groups of atoms.

These are known as the Cahn-Ingold-Prelog priority sequence rules and their importance can only be fully understood when dealing with the isomerisms described in sections E/Z Isomerism and R/S optical Isomerism. A brief description of the first two rules are given below, which is all you need for pre-university courses.

Below is an explanation of how to apply the Cahn-Ingold-Prelog priority rules devised in the 1960s by Robert Cahn, Chris Ingold and Vladimir Prelog and now accepted by the IUPAC nomenclature system for naming isomers.

You need a periodic table to get the relevant atomic numbers.

When dealing with a C-X bond grouping, the priority of X is given by ....

Sequence priority Rule 1: The higher the atomic number of an atom the higher the priority it is assigned.

e.g. for typical non-metals _ZX (Z = proton/atomic number) encountered in organic compounds ...

X = ₅₃I > ₃₅Br > ₁₇Cl > ₁₆S > ₁₅P > ₈O > ₇N > ₆C > ₁H

Sequence priority Rule 2: If the relative priority of two groups cannot be decided by Rule 1, it shall be determined by applying Rule 1 to the next atom or sequence of atoms in the group 'X'.

e.g. for typing groupings in organic molecules where X is more than one atom ....

X = -CH₂CH₂CH₃ > -CH₂CH₃ > -CH₃ > -H i.e. the longer the hydrocarbon carbon chain the higher its priority,

in terms of atomic numbers we are dealing with: ₆C₆C₆C > ₆C₆C > ₆C > ₁H

(this is my style of presenting the priority rule sequence using subscript atomic numbers on the chemical symbol)

and a more varied situation where from 1-3 atoms in the X sequence must be considered .... X =

-I > -Br > -Cl > -CH₂Br > -CH₂Cl > -CH₂-O-CH₃ > -CH₂-O-H > -CH₂CH₂Br > -CH₂CH₂Cl > -CH₂CH₃ > -CH₃ > -H

and presenting a similar sequence, but emphasising atoms which actually decide the priority from rules 1 & 2

atom priority sequence: -I > -Br > -Cl > -C-Br > -C-Cl > -C-O-C > -C-O-H > -C-C-Br > -C-C-Cl > -C-C-H > -C-H > -H

These two rules will be applied below in the case of the notation for E/Z isomerism and on a separate page for R/S optical isomerism (R/S notation for enantiomers) and this rules section will be referred back to as examples of these isomerisms are described.

Please note that for UK pre-university chemistry courses, no knowledge of the Cahn-Ingold-Prelog priority sequence rules is expected beyond the two rules above.

In many cases just knowing -H has the lowest priority is sufficient to assign the E or Z isomer in E/Z stereoisomerism.

Some pre-university examinations may require a working knowledge of the R/S notation for optical R/S stereoisomerism?

TOP OF PAGE and sub-index

14.2(c) Introduction to E/Z Stereoisomerism (geometrical/geometric - cis/trans isomerism)

Why do we have E/Z isomers? followed by a few examples in applying the assignment rules

Molecules of the same molecular formula, exhibit E/Z stereoisomerism, that is spatially different molecules (E/Z isomers) because of the inhibited/restricted rotation about at least one bond due to too high an energy requirement.

E/Z isomers are molecules that are fixed into their different spatial positions with respect to one another due to restricted rotation about a bond.

e.g. a double bond, a ring structure and often involving a planar arrangement of atoms (which doesn't have to involve a double bond or ring). Typical examples are seen in alkenes, cyclic hydrocarbons, and square planar complexes in transition metals.

To break open a double bond (C=C), breaking the pi bond, may take up to 270 kJ/mol, hence the restriction on rotation.

and Apart from ring structures, there is usually free rotation about a single carbon-carbon bond e.g. in ethane the two 'methyl' CH₃ groups can rotate independently of each other, BUT not the CH₂ groups in ethene, or any other groups attached to a C=C bonding system in any alkene molecule, without breaking a strong C-C pi bond.

The π and σ bonds of the C=C double bond

The sigma bond is present between all the atoms in organic molecules.

In most molecules, apart from the C-C bonds in a ring, there is free rotation about a single C-C bond.

However in alkenes, the double bond consists of a sigma bond and a pi bond.

Two electrons are in the molecular orbital of the sigma bond which is directed linearly between the two carbon atoms - formed from the overlap of s or p orbitals.

BUT, the other two electrons of the double bond are in the pi bonding orbitals which lie above and below the plane of the sigma bonds of the >C-C< system. It is the presence of these pi orbitals that restrict the rotation about the double bond.

The pi bond inhibits rotation because of the electron overlap both above and below the plane of the atoms, in order to rotate about the double bond you need to break the pi bond which requires a very high activation energy.

Do NOT say rotation is impossible, but it is the high 'activation' energy barrier that causes the existence of the two spatially distinct E/Z isomers that do not easily interchange!

Apart from the two sequence priority rules above which also apply to R/S optical isomerism, the specific E/Z isomerism positional assignment rule is as follows, and essential for understanding the rest of the page and is actually quite simple to apply!

For each pair of substituent groups on each carbon of the C=C double bond you need to assign a higher and lower priority based on the atomic number or sequence of atomic numbers (as described above).

Several examples are described below following on from a simple schematic representation of the E/Z positional assignment rule of higher and lower priority based on the two sequence rules explained above.

Atomic numbers: H = 1, C =12, Cl = 17, Br = 35 for the two particular E/Z isomerism examples below.

Below, I have shown schematically how to assign the E/Z notation based on the higher/lower priority atoms/groups.

So, E/Z isomerism is an example of stereoisomerism, where isomers of a particular molecular formula can exist in two or more forms of different spatial orientation which are NOT mirror images.

In these first few examples I explain how to use the priority rule to decide which isomers is E or Z.

Example (1) CH₃-CH=CH-CH₃

On the right diagram are the two E/Z isomers of but-2-ene.

(I've added the now 'maybe' defunct cis/trans notation).

Substituent group/atom priority: ₁H > ₆CH₃

The Z isomer would be named as Z-but-2-ene (cis but-2-ene).

The Z isomer has the two highest priority groups on the same side of the double bond.

The E isomer. would be named E-but-2-ene (trans but-2-ene)

The E isomers has the two highest priority groups diagonally across the double bond from each other, so they are on different sides of the double bond.

These isomers, and all other E/Z isomers are also referred to as diastereoisomers.

Diastereoisomerism is defined as where stereoisomers exist, of the same molecular formula, they have different spatial arrangements which are not mirror images of each other.

Mirror image isomerism is called R/S ('optical') isomerism. See R/S Optical Isomerism (separate page)

Note that but-1-ene, CH₃-CH₂-CH=CH₂, cannot form E/Z isomers because the are two identical groups (-H) on the right-hand end carbon atom of the double bond.

It would be the same with 2-methylpropene (CH₃)₂C=CH₂, no E/Z isomers possible because of the two methyl groups attached to the same carbon atom of the double bond.

Examples (2) to (4) are initial sketched out as thinking diagrams for more complicated examples, but the skeletal formulae are shown too.

(2) If the two highest priority groups are on the same side of the >C=C< bond network planarity that gives you the Z isomer (old notation - cis in limited cases if lower = H). So, in terms of higher and lower priorities, for the Z isomer we have ...

higher				higher
	\		/
		C=C
	/		\
lower				lower

Z isomer rule

was called cis in old notation for '1,2' disubstituted alkenes

Cl				Cl
	\		/
		C=C
	/		\
H				H

Z-1,2-dichloroethene

cis-1,2-dichloroethene

priority ₁₇Cl > ₁H

CH₃CH₂				Br
	\		/
		C=C
	/		\
CH₃				Cl

Z-1-bromo-1-chloro-2-methylbut-1-ene

left priority ₆C₆C > ₆C (CH₃CH₂ > CH₃)

and on the right carbon ₃₅Br > ₁₇Cl

Or you can say the two lowest priority atoms/groups are on the same side of the plane of the double bond >C=C<

The skeletal formulae for examples (a) and (b)

(3) If the two highest priority groups are diagonally on opposite sides of the >C=C< bond network planarity, that gives you the E isomer (old notation - trans in limited cases if lower = H). So, in terms of higher and lower priorities, for the E isomer we have ...

higher				lower
	\		/
		C=C
	/		\
lower				higher

E isomer rule

was called trans in old notation for '1,2' disubstituted alkenes

Cl				H
	\		/
		C=C
	/		\
H				Cl

E-1,2-dichloroethene

trans-1,2-dichloroethene

priority ₁₇Cl > ₁H

CH₃CH₂				Cl
	\		/
		C=C
	/		\
CH₃				Br

E-1-bromo-1-chloro-2-methylbut-1-ene

left priority ₆C₆C > ₆C (CH₃CH₂ > CH₃)

and on the right carbon ₃₅Br > ₁₇Cl

Or you can say the two lowest priority atoms/groups are diagonally on the opposite sides of the plane of the double bond >C=C<.

(4) An example of an alkene exhibiting E/Z isomerism with four different groups attached to the C=C double bond.

Br				F
	\		/
		C=C
	/		\
Cl				I

E-1-bromo-1-chloro-2-fluoro-2-iodoethene

priority ₅₃I > ₃₅Br > ₁₇Cl > ₉F

Br				I
	\		/
		C=C
	/		\
Cl				F

E-1-bromo-1-chloro-2-fluoro-2-iodoethene

priority ₅₃I > ₃₅Br > ₁₇Cl > ₉F

The skeletal formulae would be written as

NOTE: The IUPAC recommend that the terms geometrical/geometric isomerism are NOT used but to use the stereoisomerism classification terms E/Z stereoisomerism or E-Z isomerism.

The E/Z notation is replacing the limited cis/trans notation in assigning names to a particular stereoisomer.

However cis/trans nomenclature is in widespread use so it will be acknowledged in parallel with the E/Z convention where appropriate.

TOP OF PAGE and sub-index

14.2(d) E/Z isomers of some hydrocarbon alkenes and halogenated alkenes

Note: cis-trans isomerism is sometimes defined as a special type of E/Z isomerism in which there is a non-hydrogen group and a hydrogen atom attached to each C of a C=C double bond.

This means the cis isomer is the Z isomer with the H atoms on each carbon on the same side and the trans isomer will be the E isomer with the hydrogens on opposite sides of the double bond.

BUT, the terms cis and trans are sometimes applied to where there are only two substituents like cis/trans 1,2-dichloroethene (above) and cis/trans but-2-ene. At other times, if the same substituent is on both carbon atoms of the C=C bond, if both of these substituents are on the same side its the cis isomer, if diagonally across the double bond its the trans isomer.

The terms cis/trans have been quite loosely used, which is why the E/Z system is the best and recommended by the IUPAC, so you must know how to use the E/Z rules and correctly designate the E or Z isomer, it covers anything you will come across.

I've started off by repeated the but-2-ene example in more detail.

A simple example: but-2-ene

(priority -CH₃ > -H)

The E (trans) ,

(ball and stick model 2), and the

Z (cis) isomer ,

(ball and stick model 1)

both E/Z isomeric forms of but-2-ene

However, in order for E/Z stereoisomers to exist there must be two different atoms/groups attached to both carbon atoms of the C=C carbon double bond or two adjacent carbons in a substituted cycloalkane.

Note that E-but-2-ene and Z-but-2-ene are NOT mirror images of each other.

If the groups are not different, they have the same priority!

This is why structural isomer methylpropene (model 3 above) cannot exhibit E/Z isomerism, both carbon atoms of the double bond have the same two atoms/groups attached to them.

Again, this is why but-1-ene , with two hydrogens on the right-hand carbon of the double bond, cannot exhibit E/Z isomerism, but it is a structural isomer of the E/Z isomers of but-2-ene and methylpropene.

The same argument applies to 2-methylbut-2-ene It has two methyl groups attached to the same right-hand carbon atom of the C=C double bond, you cannot make two spatially different molecules. However the isomeric pent-2-ene would exhibit E/Z isomerism.

Note

(i) that you cannot superimpose one E/Z isomer on the other - proof they are spatially different isomers.

(ii) the structural formula cannot be used to indicate E/Z isomers, the molecule must be represented by the full displayed 2D/3D structural formula.

The three most common situations you are likely to encounter are >C=C< or a >C=N- double bond and around a C-C single bond in cycloalkanes. In both cases the energy required is too high to allow free rotation around the double bond BUT free rotation is possible around single bonds (C-C, C-O etc.) e.g. alkyl groups around the C-C single bonds in non-cyclo linear/branched alkanes.

If two identical atoms/groups are attached to the same carbon atom of a C=C double bond, you cannot have geometrical isomers e.g. those with R₂C=C< or R₂C=N- where R = R. See the diagram below.

The 'old' nomenclature term cis often means the same substituents are on the same side of the double bond and trans when they are on opposite sides. Under the E/Z notation cis is now Z and trans is now E.

In a sense cis/trans isomers were a special case of a substituent and a hydrogen atom on each carbon of the C=C double bond.

E/Z configuration assignment is absolutely necessary when there 3 or 4 different substituents on the C=C group (again, see the diagram below)

Shown below are some more introductory exemplar diagrams to illustrate whether E-Z isomers can exist or not and how to use the modern E/Z isomerism notation-designation-assignment of absolute configuration.

Diagram explaining E/Z isomerism (old cis/trans) configuration nomenclature

Lower left example: (E)-1-bromo-1-chloropropene and (Z)-1-bromo-1-chloropropene

Lower right example: E-3-methylpent-2-ene and Z-3-methylpent-2-ene (repeated further down with skeletal formulae)

To understand the two lower left and right examples apply the Priority Rules to alkenes for E/Z ('geometrical') isomerism:

For each carbon of the double bond the higher priority atom/group is worked out.

The Z isomer is where both highest priority groups are on the same side of the double bond (includes all cis configurations of the old convention).

The E isomer is where the two highest priority atoms/groups are diagonally opposite each other on different sides of the plane of the double bond system (includes all trans isomers of the old convention).

(Note: In terms of the two highest priority atoms or groups, E, 'on opposite sides', comes from the German word entgegen, meaning 'opposite' and the Z 'on the same side' comes from the German word zusammen meaning 'together')

More alkene examples of E/Z isomerism

3-methylpent-2-ene, can be drawn as E/Z isomers using structural and skeletal formula
, , E-3-methylpent-2-ene

and , Z-3-methylpent-2-ene

Note the priority order CH₃CH₂ > CH₃ > H from the Cahn-Ingold-Prelog priority rules (₆C₆C >₆C > ₁H)

the E/Z isomers of

Z-hept-2-ene and E-hept-2-ene (cis and trans hept-2-ene)

Cahn-Ingold-Prelog priority rule: CH₃CH₂CH₂CH₂ > CH₃ > H

and the E/Z isomers of

E-3-methylhex-3-ene and Z-3-methylhex-3-ene

Cahn-Ingold-Prelog priority rule: CH₃CH₂ > CH₃ > H (₆C₆C >₆C > ₁H)

4-methylpent-2-ene, , has E/Z isomers:

Z/cis- , , E/trans- ,

Cahn-Ingold-Prelog priority rule: (CH₃)₂CH- > CH₃- > H- (₆C₆C >₆C > ₁H)

Z-4-methylpent-2-ene and E-4-methylpent-2-ene

3,4-dimethylpent-2-ene,

has two E/Z isomers: E-3,4-dimethylpent-2-ene , and Z-3,4-dimethylpent-2-ene

Cahn-Ingold-Prelog priority rule: (CH₃)₂CH- > CH₃- > H- (₆C₆C >₆C > ₁H)

4,4-dimethylpent-2-ene, E/Z isomers:

Z/cis- , and E/trans-

Cahn-Ingold-Prelog priority rule: (CH₃)₃CH- > CH₃- > H- (₆C₆C >₆C > ₁H)

3-ethylpent-2-ene, ,

no E/Z isomers because there are two identical (ethyl) groups attached to the same (left) carbon of the double bond

Hex-2-ene,

Z-hex-2-ene / cis-hex-2-ene , , and

E-hex-2-ene / trans-hex-2-ene, ,

Cahn-Ingold-Prelog priority rule: CH₃CH₂CH₂- > CH₃- > H- (₆C₆C >₆C > ₁H)

hept-3-ene, ,

has two E/Z isomers: Z-hept-3-ene / cis-hept-3-ene

and E-hept-3-ene / trans-hept-3-ene

Cahn-Ingold-Prelog priority rule: CH₃CH₂CH₂- > CH₃CH₂- > H- (₆C₆C₆C >₆C₆C > ₁H)

TOP OF PAGE and sub-index

14.2(e) Further case studies of E/Z stereoisomerism

BUT, now including discussing similarities & difference in physical & chemical properties of the E/Z isomers

Case studies of E/Z (geometric) isomerism:

2a.1 C₄H₈ * 2a.2 HOOC-CH=CH-COOH * 2a.3 ClCH=CHCl * 2a.4 di-substituted cycloalkanes

2a.5 azo (-N=N-) and R₂C=N-X compounds * 2a.6 Dienes * 2a.7 Trans fats

2a.8 But-2-enoic acid and 2-methylbut-2-enoic acid * 2a.9 Organic analogues of the anti-cancer drug cis-platin

2a.10 Cis/trans retinal - biochemistry of the eye * Definition of diastereoisomers

Case study 2a.1 Isomers of C₄H₈, cis/trans or Z/E-but-2-ene and other alkenes

Ball and stick models for three isomers of C₄H₈

1. Z-but-2-ene (cis isomer), 2. E-but-2-ene (trans isomer), 3-methylpropene (cannot exhibit E/Z isomerism)

Priority order: -CH₃ > H (since at. no. of carbon 6 > 1 for hydrogen)

(1) Z-but-2-ene (cis) (bpt 4^oC) , , (Z-2-butene)

The Z isomer has the two highest priority groups on the same side of the plane of the C=C double bond.

(2) E-but-2-ene (trans) (bpt 1^oC), , (E-2-butene)

The E isomer has the two highest priority groups on opposite sides of the carbon = carbon double bond.

(1) and (2) are very similar physically (e.g. colourless gases and very low bpt) and chemically (e.g. alkene electrophilic addition reactions).

Note that there are four other physically similar isomers of C₄H₈ namely,

(3) 2-methylpropene (bpt -7^oC, chain isomer)

(4) but-1-ene (bpt -6^oC, position of C=C isomer)

(5) methylcyclopropane and (6) cyclobutane (bpts 5^oC and 13^oC, and are alkane functional group isomers of alkenes 1 to 4)

BUT non of (3) to (6) can form E/Z isomers.

(3) and (4) would be chemically similar to (1) and (2) being alkenes and undergo many addition reactions,

but (5) and (6) have no 'alkene' chemistry but just the limited chemistry of alkanes e.g. uv chlorination as well as the combustion, which they all readily undergo!

Similarly ...

, , E-3-methylpent-2-ene

and , Z-3-methylpent-2-ene

BUT , 2-methyl-2-pentene does NOT exhibit E/Z isomerism because two identical (CH₃) groups are attached to the same carbon atom of the double bond.

and

4,4-dimethylpent-2-ene, has two E/Z isomers:
Z-4,4-dimethylpent-2-ene (cis), and E-4,4-dimethylpent-2-ene (trans)

TOP OF PAGE and sub-index

Case study 2a.2 trans/cis or Z/E-but-2-ene-1,4-dioic acid, HOOC-CH=CH-COOH

(butenedioic acids, old names given below). Substituent group priority -COOH > H

On heating the trans form (1) fumaric acid) now called E-but-2-ene-1,4-dioc acid, it proves difficult to change it into the cyclic anhydride (3) below.

Z-but-2-ene-1,4-dioc acid (2) cis form, maleic acid (3) + H₂O

E/Z isomers of but-2-ene-1,4-dioc acid cis/trans fumaric acid maleic acid advanced level organic chemistry

The skeletal formulae of the three molecules mentioned

However, if the Z(cis) form (2) is heated, it readily changes into the cyclic acid anhydride (3).

Not only does the restricted rotation about the C=C bond cause the existence of E/Z geometrical isomers, but in this case you can only readily get the elimination of water when the two -OH groups are on the same side of the planar >C=C< system, as in the cis/Z form (2).

In the trans/E form (1) the elimination reaction is stereochemically hindered because the -OH so far apart.

However, both (1) and (2) undergo the same electrophilic addition reactions of the 'alkene' double bond, >C=C< and the same reactions of the carboxylic acid group -COOH.

Some physical differences.

*Sometimes the trans isomer has the higher symmetry and packs more closely into a crystal lattice, increasing the intermolecular forces, and this tends to increase melting points and density but decrease solubility as solvation is not as energetically favourable.

The physical differences may be partially explained by the different polarities of the molecules and the orientation of hydrogen bonding, either in the crystal lattice or when dissolved in water.

(* unfortunately, there are many exceptions to this 'rough rule of thumb', so beware).

(1) The E/trans form: d = 1.64 gcm^-3, solubility in water 0.7g/100 cm³ at 25 ^oC, melting point 287 ^oC,

(2) The Z/cis form: d = 1.59 gcm^-3, solubility in water 78.8g/100 cm³ at 25 ^oC, melting point 130 ^oC,

TOP OF PAGE and sub-index

Case study 2a.3 Physical properties of cis/trans or Z/E-1,2-dichloroethene

Ball and stick models of halogenated ethene molecules.

1. 1,2-dichloroethene H₂C=CCl₂, 2. 2-bromo-1,1-dichloroethene CCl₂C=CHBr (neither can exhibit E/Z isomerism)

3. E-1,2-dichloroethene (trans stereoisomer of ClCH=CHCl), 4. Z-1,2-dichloroethene (cis isomer of ClCH=CHCl)

The C^δ+-Cl^δ- bond is polar due to the difference in electronegativity between carbon and chlorine (Cl > C) and this partially accounts for the small differences in physical properties.

(1) Z-1,2-dichloroethene (cis) d = 1.265 gcm^-3, mpt -80 ^oC, bpt 60 ^oC, dipole moment 1.89_D, with both Cl's on the same side of the C=C bond, the combined effect of the two polar C-Cl bonds makes it a much more polar molecule and raises the bpt compared to (2), but not the mpt (not sure why, subtlety of the crystal structure?).

Cahn-Ingold-Prelog priority rule: ₁₇Cl > ₁H

(2) E-1,2-dichloroethene (trans) d = 1.259 gcm^-3, mpt -50 ^oC, bpt 48 ^oC, dipole moment 0.00_D, the effect of the C-Cl polar bonds cancel each other out giving a relatively non-polar molecule,

and there is positional isomer (3) shown below.

(3) d = 1.218 gcm^-3, mpt -? ^oC, bpt 32 ^oC, dipole moment 1.30_D?, 1,1-dichloroethene, is a positional isomer of the two geometrical isomers and cannot exhibit E/Z isomerism because two identical groups (H's or Cl's) are attached to the same carbon of the double bond.

The skeletal formulae of the three molecules mentioned.

All three isomers are chemically similar e.g. the electrophilic addition reactions of alkenes.

TOP OF PAGE and sub-index

Case study 2a.4 of E/Z isomerism with 1,2- or 1,3-disubstituted cycloalkanes - examples based on cyclopropane, cyclobutane, cyclopentane and cyclohexane

E/Z isomers can exist in 1,2-disubstituted cyclopropanes* and cyclobutanes* because the -C-C- ring structure inhibits rotation about the C-C bonds.

These are alicyclic compounds - cyclo-aliphatic compounds with a carbon chain ring of =>3 carbon atoms.

In order to change from one E/Z isomer to another, you would have to break at least one strong covalent bond e.g. the C-C bond of the ring itself.

* Alicyclic compounds means cyclo-aliphatic.

If the 1,2-substituents are on the same side of the plane of the triangle/square of carbon atoms you get the Z (cis) form, if the are on opposite sides you get the E (trans) form.

Disubstituted cyclopropanes

(1) 1,2-dichlorocyclopropane can give E/Z isomers and the group priority is Cl > H

Z-1,2-dichlorocyclopropane (cis), both highest priority groups on the same side of the 'plane' of the cyclopropane ring.

Cahn-Ingold-Prelog priority rule: ₁₇Cl > ₁H

and E-1,2-dichlorocyclopropane (trans), the highest priority groups are on opposite sides of the 'plane' of the cyclopropane ring.

to help you think in 3D!

(2) 1,1-dichlorocyclopropane is a positional isomer of C₃H₄Cl₂, and cannot exhibit geometrical isomerism.

Disubstituted cyclobutanes

(3) 1,2-dibromocyclobutane, likewise can give ...

(Z isomer, cis) and (7) (E isomer, trans)

(4) or (9) 1,1-dibromocyclobutane, is a positional isomer of C₄H₆Br₂ and cannot exhibit E/Z (geometrical) isomerism because the two bromine atoms are attached to the same carbon.

(5) 1,3-dibromocyclobutane is also positional isomer of C₄H₆Br₂ and can exhibit E/Z (geometric) isomerism.

Z/cis , with the two Br atoms on same side of the plane of the C4 ring,

and E/trans with the two Br atoms on each side of the plane of the cyclobutane ring.

Note 1: The molecular formulae C₃H₄Cl₂ and C₄H₆Br₂ can theoretically give rise to other functional group/positional/E/Z (trans/cis) isomers in the form of non-cyclic alkenes e.g.

(6) ClCH₂CH=CHCl (1,3-dichloropropene)

or (7) CH₃CHBr=CHBrCH₃ (2,3-dibromobut-2-ene) etc. etc!

both of which can exhibit E/Z isomerism.

Note 2: Strictly speaking the 4 carbon ring of cyclobutanes is NOT planar, in fact the 'V' of two of the carbon atoms is bent at 26^o from the 'V' of the other two carbons. However, using planar projections it is possible to work out and illustrate the E/Z isomers of cyclobutanes.

Disubstituted cyclopentanes - dichlorocyclopentanes (ball and stick models below)

1. Chlorocyclopentane C₅H₉Cl: This has no stereoisomers, but is structurally isomeric with monochloropentenes.

2. 1,1-dichlorocyclopentane C₅H₈Cl₂:

This almost has a plane of symmetry and does not have any stereoisomers, but it is a positional structural isomer of C₅H₈Cl₂.

For 3. and 4. the restricted rotation about the single C-C bonds allows E/Z stereoisomers to exist, they are also structural isomers of C₅H₈Cl₂.

3. Z-1,2-dichlorocyclopentane C₅H₈Cl₂:

This is the Z isomer (cis in old terms).

Both chlorine atoms are above the 'almost' flat plane of the ring of five carbon atoms.

The carbon atoms of the C-Cl bonds are also chiral, so the molecule can exhibit R/S isomerism.

4. E-1,2-dichlorocyclopentane C₅H₈Cl₂:

This is an E isomer (trans in old terms).

One chlorine atom is above the plane of the carbon atom ring and the other chlorine is below the plane.

Again, the carbon atoms of the C-Cl bonds are also chiral, so the molecule can exhibit R/S isomerism.

3. and 4. are formed when chlorine electrophilically adds to cyclopentene.

+ Cl₂ ====>

More advanced note:

The two C-Cl stereocentres give rise to E/Z isomerism, but they are also chiral carbon stereocentres which means there are R/S isomers.

Disubstituted cyclohexanes

e.g. the E/Z isomers of 1,2-dibromocyclohexane.

+ Br₂ ===>

Unsaturated cyclohexene readily undergoes electrophilic addition of bromine to yield saturated 1,2-dibromocyclohexane. However, the 'flat' skeletal formula doesn't tell the whole story.

Just like the other 1,2 or 1,3 disubstituted cycloalkanes, the product can exhibit E/Z isomerism.

Priority here is: ₃₅Br > ₆C > ₁H but only the Br and H need be considered.

E/Z isomerism ball and stick model for Z-1,2-dibromocyclohexane isomer Z-1,2-dibromocyclohexane cis trans molecular structure advanced organic chemistry doc brown

A good excuse to play with my model kit, its the only toy I possess!

skeletal formula diagram for E/Z cis/trans isomerism with 1,2-dibromocyclohexane trans E isomer cis Z isomer of a disubstituted cyclohexane geometric isomerism

A conventional simplified 2D diagram, but remember the hexagonal ring of carbon atoms is NOT planar (more 'chair' shaped), never-the-less it is ok to talk about and 'above' and 'below' the ring to distinguish the spatial positions of the bromine atoms.

The Z (cis) and E (trans) isomers of 1,2-dibromohexane. The two bromine atoms have the highest priority. 2D diagram

For both diagrams: on the left is Z-1,2-dibromocyclohexane, with both two bromine atoms above the hexagonal ring (which isn't quite planar - in fact all the C-C-C, C-C-H, H-C-H, C-C-Br and H-C-Br bond angles are ~109^o).

On the right is E-1,2-dibromocyclohexane, with one bromine atom above the hexagonal ring and one bromine atom below the hexagonal ring.

Similar to the previous example, the two C-Br stereocentre carbon atoms give rise to E/Z isomers, but they are also chiral carbon stereocentres which means there are R/S isomers too.

In fact both E/Z isomers have the two R/S isomers (enantiomers) and this applies to all 1,2-disubstituted cyclohexane molecules, so things are quite complicated and a full analysis is beyond the scope of pre-university organic chemistry.

TOP OF PAGE and sub-index

Case study 2a.5 Isomerism in azo (-N=N-) and R₂C=N-X compounds

Organic (or inorganic) compounds of the structure R-N=N-R' (e.g. aromatic azo dyes) can exist as cis and trans isomers in just the same way as alkenes, where R or R' = H, alkyl, aryl group etc.

R can be different or the same as R'.

Stereochemically, the lone pairs on the nitrogen effectively behave as an atom bonding pair of electrons in determining the trigonal planar orientation of the -N= bonds and the lone pair of electrons on the nitrogen.

Three groups of electrons around an atom X, always give a trigonal planar arrangement around the central atom >X-.

The double bond, N=N or C=N, ensures that too high an energy is required for ready rotation about the double bond.

The Z/cis and E/trans forms will have different physical properties such as melting/boiling points.

Examples of -N=N- systems:

(1) (Z/cis) and (2) (E/trans)

(all R-N=N-R' bond angles are about 120^o)

Examples of >C=N- systems

Carbonyl compounds like aldehydes and ketones undergo condensation reactions of the type

RR'C=O + H₂N-X ==> RR'C=N-X + H₂O

where R is different to R' and = H, alkyl or aryl etc. geometrical isomers can occur.

and when X= H (ammonia), alkyl (aliphatic primary amine), aryl (aromatic primary amine), OH (hydroxylamine), NH₂ (hydrazine), NHC₆H₃(NO₂)₂ (2,4-dinitrophenylhydrazine). If for (3) and (4) if in priority R' > R (e.g. CH₃CH₂ > CH₃)

(3) (Z/cis) and (4) (E/trans)

(i.e. R' as a higher ranking group than R)

When R = R' i.e. (5) geometrical isomerism is not possible.

(Note: all >C=N-X angles are about 120^o)

Case Study 2a.6 Dienes can also exhibit E/Z stereoisomerism

, Z-buta-1,3-diene (cis), unstable, 2%, low activation of rotation to give the E isomer.

and

, E-buta-1,3-diene (trans), much more stable, 98%, in dynamic equilibrium with the Z isomer.

In this case the E/Z designation is based on the central C-C single carbon-carbon bond and therefore rotation is much easier and the E stereoisomer is the more stable configuration.

TOP OF PAGE and sub-index

Case study 2a.7 Trans fats

Many natural oils and fats are esters of propane-1,2,3-triol (glycerol) and long saturated and unsaturated chain fatty acids - sometimes referred to as triglyceride esters.

Animal fats can be mainly saturated, but vegetable oils are unsaturated. Any unsaturated fats or oils can exist as E/Z isomers (trans/cis isomers). The terms mono, di or tri-unsaturated fatty acids refer to the number of alkene groups in the fatty acid.

In the natural oils the component fatty acids are the Z isomers (cis isomers) and are considered to be healthy in your diet.

Each carbon of the C=C double bond has one hydrogen atom attached to it.

However, when an unsaturated oil or fat is partially hydrogenated with a nickel catalyst some of the double bonds are broken.

This allows rotation around a single carbon-carbon bond, the double bond reforms and the E isomer (trans isomer) is formed - the more unhealthy E/Z isomer!

These trans fatty acids are considered more harmful in your diet than the original cis fatty acids.

Diagram showing the structure of a typical triglyceride ester of saturated, monounsaturated and polyunsaturated fatty acids. A possible change from the Z- (cis) linkage to an E- (trans) linkage is shown.

Comparison of oil and fat structures not showing the stereochemical structure

Animal fats are mainly saturated fats with no carbon = carbon double bonds in the fatty acid chain and are low melting solids at room temperature.

The 'long–chain fatty acids' can be unsaturated, with one or more C=C double bonds, and so forming unsaturated oils or fats e.g. the triglyceride formed from oleic acid. Vegetable oils are usually viscous liquid at room temperature.

A simple (non-stereochemical) diagram showing several points of 'unsaturation' - the C=C carbon-carbon double bonds in the fatty acid chain.

TOP OF PAGE and sub-index

Case study 2a.8 But-2-enoic acid and 2-methylbut-2-enoic acid

These are monounsaturated monocarboxylic acids.

The E/Z isomers of but-2-enoic acid:

The E/Z (trans/cis) isomers of but-2-enoic acid, structural formula, CH₃CH=CHCOOH

E/Z isomers of but-2-enoic acid cis trans crotonic acid isocrotonic acid advanced level organic chemistry

The priority rule for E/Z assignment: ₈O₆C (COOH) > ₆C (CH₃) > ₁H

E-but-2-enoic acid (trans isomer), melting point 70-73^oC, boiling point 185-189^oC, density 1.02 g/cm³, pK_a = 4.69

It has the higher melting point because the molecules can pack more closely together than the Z isomer, so increasing the intermolecular forces, hence increase in both melting and boiling point.

Z-but-2-enoic acid (cis isomer), melting point 15^oC, boiling point 168-169^oC, density 1.03 g/cm³, pK_a = ?

It has the lower melting point because the molecules cannot pack more closely together than the E isomers, so decreasing the intermolecular forces - with both the methyl group and the carboxylic acid group on the same side of the >C=C< bond the molecules are pushed a bit further apart.

The E/Z isomers of but-2-enoic acid will have different crystal structures, with differences in intermolecular forces, leading to different physical properties like melting point, boiling point and density, but the solubility in water would remain the same.

You would expect them to have very similar chemical reactions e/g/ of the alkene group or carboxylic acid group.

The E/Z isomers of but-2-enoic acid: a similar situation to but-2-enoic acid

E/Z isomerism (trans/cis) geometric isomers of 2-methylbut-2-enoic acid Tiglic acid Angelic acid

The E/Z (trans/cis) isomers of 2-methylbut-2-enoic acid, structural formula, CH₃CH=C(CH₃)COOH

The priority rule for E/Z assignment: ₈O₆C (COOH) > ₆C (CH₃) > ₁H

E-2-methylbut-2-enoic acid (trans form, commonly known as Tiglic acid)

Tiglic acid is found in croton oil (from the seeds of the Croton tiglium tree) and is volatile crystallisable material with a sweet, warm and spicy odour.

It is carcinogenic and is used in cancer research.

Tiglic acid melts at 64^oC, higher than Angelic acid, pK_a = 4.96, slightly soluble in cold water.

Z-2-methylbut-2-enoic acid (cis form, commonly known as Angelic acid)

Angelic acid is found as the acid or as an ester in the roots of the Angelica archangelica plant.

Angelic esters are active components in many herbal medicines for gout, fevers and pains.

It readily isomerises to give the trans Tiglic acid.

Angelic acid is a volatile solid with a biting taste and pungent sour odour and forms colourless crystals.

Angelic acid is a volatile solid with a biting taste and pungent sour odour and forms colourless.

It melts at 46^oC and pK_a = 4.97, both isomers of similar weak acid strength, slightly soluble in hot water.

Angelic acid melts at a lower temperature than Tiglic acid because its molecules cannot pack as closely together as those in Tiglic acid.

The decreasing the intermolecular forces - with both the methyl group and the carboxylic acid group on the same side of the >C=C< bond, the molecules are pushed a bit further apart, reducing the intermolecular forces, reducing the energy needed for any phase change.

Tiglic acid and Angelic acid are both produced in the defensive secretions of many beetles.

Its amazing how the same molecules crop in quite different living organisms - molecular evolution!

TOP OF PAGE and sub-index

2a.9 Organic analogues of the anti-cancer drug cis-platin

Platinum(II) complexes are used to prepare anti–cancer drugs used in chemotherapy. One example is the compound cis–diamminedichloroplatinum(II), [Pt(NH₃)₂Cl₂]⁰, (known as cisplatin). Cisplatin is a much more effective anti-cancer drug than transplatin.

Cis-platin (Z-platin) and trans-platin (E-platin), square planar neutral complexes. The square planar bond arrangement allows the existence of E/Z isomers, which would not exist if the bonds around the platinum ion where arranged tetrahedrally. For more see my Transition metal notes on platinum

Many organic analogues have, and are, being tested for their anti-cancer properties, by replacing the ammonia group with an aliphatic amine or more complex amines that can act as an electron pair donating ligand.
A huge number of Pt(II) complexes have been synthesised, many with the general formula [(RR'HN:)₂PtCl₂], where R and R' are organic groups, R and R' can be the same e.g. the 'simple' E (trans) and Z (cis) complexes with ethylamine and 1,2-diaminoethane (monodentate and bidentate ligand) shown below, but many have much more complicated organic ligands.

cis Z anti-cancer drugs of platinum(II) complexes ligands chloride ethylamine 1,2-diaminoethane ethylenediamine

In most case the Z (cis) E/Z isomer is the most effective as an anti-cancer chemotherapeutic agent but the medical situations are complex and chemotherapy has its obvious side-effects like loss of hair.
A bit of biochemistry: These complexes interfere with the DNA repair mechanisms in a cell and the DNA damage causes the cancer cell to undergo apoptosis - a kind of cell death, thus preventing cell division.

TOP OF PAGE and sub-index

2a.10 Cis/trans retinal - a biochemistry aspect of the eye (amazing! - fascinating!)

Retinal (retinaldehyde) is a complex unsaturated aliphatic aldehyde that is found in the receptor cells of the retina in the human eye.

The extended alternating C-C single and C=C double bond system forms the basis of the conjugated chromophore - in fact the pi orbital overlaps will also include the C=O bond of the aldehyde group.

Retinal molecules are bound to proteins called opsins, and the chemical basis of visual phototransduction, the light-detection stage of visual perception (vision).

Retinal is an example of where E/Z isomerisation has an important biological role and involves the interchange of the E and Z isomers (trans and cis) of retinal.

Retinal is the light-sensitive component of rod and cone photoreceptors in the retina of the eye.

When cis-retinal absorbs a photon of visible light the pi bond breaks and trans-retinal is formed (in 2 x 10^-11 seconds).

This configuration change pushes against an opsin protein in the retina, which triggers a chemical signalling cascade, which can result in perception of light or images by the human brain.

In other words the change in shape of the retinal molecules causes a nerve impulse to be sent to the brain.

cis-retinal trans-retinal Z-retinal E-retinal interchange transformation via light photon enzymes biochemical change in rod & cone receptors of retina of human eye

The above simplified diagram (adapted from Wikipedia) shows the molecular, and reversible, transformation between Z-retinal (cis-retinal) and E-retinal (trans-retinal) triggered by a single photon.

An enzyme can then transform the trans-retinal back into cis-retinal, which can then interact again with another incoming photon of visible light impacting on the retina.

The absorbance spectrum of the chromophore depends on its interactions with the opsin protein to which it is bound, so that different retinal-opsin complexes will absorb photons of different wavelengths (i.e., different colours of light). See the absorption spectra of the rod and cone photopigments of the eye.

Diastereomers (in case you come across the terms):

Diastereomers (diastereoisomers) are a type of a stereoisomer.

Diastereomers are defined as non-mirror image non-identical stereoisomers

Diastereomerism occurs when two or more stereoisomers of a compound have different configurations at one or more of the equivalent stereocenters and are NOT mirror images of each other.

E/Z isomers are examples of diastereoisomers, and, as you will see, they are NOT mirror images of each other (BUT R/S isomerism does involve non-superimposable mirror image molecules.

I will not being using these terms again on this page and I don't think they are needed for UK A Level Chemistry.

what is stereoisomerism in organic chemistry? what are cis/trans isomers? why can E/Z isomers exist? why is the interconversion of cis/trans isomers difficult? describe how to use the Cahn-Ingold-Prelog priority sequence rules for E/Z (sis/trans isomers), how do you define stereoisomerism for E/Z or cis/trans isomers of a given molecular formula? give the names and structures of the E/Z cis/trans isomers of molecular formula C4H8 butenes, give the names and structures of the E/Z cis/trans isomers of molecular formula C3H4BrCl, give the names and structures of the E/Z cis/trans isomers of molecular formula C6H12 alkenes, give the names and structures of the E/Z cis/trans isomers of molecular formula C7H14 heptenes, give the names and structures of the E/Z cis/trans isomers of molecular formula C4H4O4 unsaturated dicarboxylic acids, give the names and structures of the E/Z cis/trans isomers of molecular formula C2H2Cl2 dichloroethene, give the names and structures of the E/Z cis/trans isomers of disubstituted cycloalkanes of molecular formula C3H4Cl2 dichlorocyclopropane, give the names and structures of the E/Z cis/trans isomers of molecular formula C4H6Br2 dibromocyclobutane, give the names and structures of the E/Z cis/trans isomerism of the isomers of azo compounds advanced level chemistry Cahn-Ingold-Prelog Priority Rules for AQA AS chemistry, Cahn-Ingold-Prelog Priority Rules for Edexcel A level AS chemistry, Cahn-Ingold-Prelog Priority Rules for A level OCR AS chemistry A, Cahn-Ingold-Prelog Priority Rules for OCR Salters AS chemistry B, Cahn-Ingold-Prelog Priority Rules for AQA A level chemistry, Cahn-Ingold-Prelog Priority Rules for A level Edexcel A level chemistry, Cahn-Ingold-Prelog Priority Rules for OCR A level chemistry A, Cahn-Ingold-Prelog Priority Rules for A level OCR Salters A level chemistry B Cahn-Ingold-Prelog Priority Rules for US Honours grade 11 grade 12 Cahn-Ingold-Prelog Priority Rules for pre-university chemistry courses pre-university A level revision notes for Cahn-Ingold-Prelog Priority Rules A level guide notes on Cahn-Ingold-Prelog Priority Rules for schools colleges academies science course tutors images pictures diagrams for Cahn-Ingold-Prelog Priority Rules A level chemistry revision notes on Cahn-Ingold-Prelog Priority Rules for revising module topics notes to help on understanding of Cahn-Ingold-Prelog Priority Rules university courses in science careers in science jobs in the industry laboratory assistant apprenticeships technical internships USA US grade 11 grade 11 AQA A level chemistry notes on Cahn-Ingold-Prelog Priority Rules Edexcel A level chemistry notes on Cahn-Ingold-Prelog Priority Rules for OCR A level chemistry notes WJEC A level chemistry notes on Cahn-Ingold-Prelog Priority Rules CCEA/CEA A level chemistry notes on Cahn-Ingold-Prelog Priority Rules for university entrance examinations with advanced level chemistry

[WEBSITE SEARCH BOX]

Website content © Dr Phil Brown 2000+. All copyrights reserved on revision notes, images, quizzes, worksheets etc. Copying of website material is NOT permitted. Exam revision summaries & references to science course specifications are unofficial.