Organic Chapter 11
Chiral Objects
-Shoe -Gloves -Screws
Not chiral
-Sock -Screwdriver -Pencil
A molecule with n chirality centers can have a maximum of how many isomers?
2n isomers (enantiomers and diastereomers combined) (Van't Hoff rule)
Alternate axis of symmetry
An alternate axis of symmetry is an axis that is perpendicular to the plane that divides the molecule into two halves. Rotation of the molecule around the axis, by any suitable angle, followed by reflection through the perpendicular plane gives the molecule that is identical to the starting one.
What does a chirality center overlap with?
An atom
What do formulas such as Lewis structures or condensed structural formulas show?
Connectivity in a molecule but do not show the spatial arrangement of the atoms
How do enantiomers rotate the plane of polarized light?
In opposite directions. The magnitude of the rotation, which is an achiral property, is the same.
In a Fischer projection the threo isomer has?
identical or similar substituents on opposite sides
In a Fischer projection the erythro isomer has?
identical, or similar, substituents on the same side of the chain
When are two molecules superimposable?
if a conformation (of any energy, including high energy conformations - for example, eclipsed conformations of alkanes or boat conformations of substituted cyclohexanes) exists in which each substituent of one molecule can be placed over the same substituent of the other molecule.
If a racemic mixture is allowed to crystallize at a low temperature
individual enantiomers may crystallize separately. The crystals are then mechanically separated from each other with an aid of a pair of tweezers and a microscope
(S)-limonene
lemon fragrance
Enantiomers
mirror images of each other
Are synthetic vitamins single enantiomers?
no
Does the fact that a compound is not optically active mean that it is not chiral
no
Is an achiral compound optically active?
no because it is composed of achiral molecules
optical purity
observed specific rotation/ specific rotation of the pure enantiomer x 100 percnt
Where should the lowest priority group be located on a Fischer Projection Formula
on a vertical bond (project away from us)
(R)-limonen
orange fragrance
Diastereomers are separated by ?
physical methods (such as crystallization or chromatography. Finally, in another reaction, the resolving agent is removed and the pure enantiomer is isolated.
What does the existence of meso form do?
reduces the number of possible stereoisomers
Meso compounds do not
rotate plane-polarized light (they are optically inactive or achiral) and they are identical to their mirror images because they can be superimposed by a 180° rotation of one structure in the plane of the paper
Standard Condition for specific rotation of a chiral compound
sample cell of 10 cm (1 dm) length and a concentration of 1 g/mL. Since the rotation also depends on the temperature and wavelength of light they also have to be reported. Usually, measurements are done at 25ºC and a source of light is a sodium lamp with a filter, which provides light of a single wavelength (589.6 nm)
Diastereomers
stereoisomers that are not mirror images of each other
Lack of any of the symmetry elements is an indication of what?
that a compound is chiral
The absolute configuration is
the actual orientation of atoms at a chirality center
positional isomers (regioisomers)
the carbon skeletons are identical, but the positions of functional groups are different
skeletal isomers
the carbon skeletons of the compounds differ
To represent the tetrahedral arrangement of the substituents?
the chirality center is in the plane of the drawing, the vertical bonds project away from the viewer and the horizontal bonds project toward the viewer. This is the so-called "bow-tie convention."
What is chirality a property of?
the entire molecule (not individual atoms) whereas a chirality center is the cause of chirality
functional isomers
the functional groups differ
What does the van't hoff rule give?
the maximum number of isomers, the actual number may be less than that
Specific rotation of a chiral compound
the rotation that was observed under the standard conditions.
But what happens if electrons are moving?
then electrons with opposite spins cannot be superimposed and they are two non-superimposable mirror images. Thus, they are chiral. They are related to each other as left and right screws.
How are optical isomers similar?
they are chemically and physically identical. This type of isomerism is called chirality and a molecule that exhibits such type of isomerism is a chiral molecule
What do optical isomers have identical properties except..?
they rotate plane-polarized light in opposite directions, and that they react differently with other optically active compounds
both optical purity and enantiomeric excess have the same values and neither has units (they cancel out in the course of calculation)
true
What do you notice when trying to superimpose enantiomers
two groups can be placed in the same orientation of both molecules but the other two substituents (H and Cl) are reversed in their spatial orientation. (wedge and dash)
To represent stereoisomers such as enantiomers on paper (in two dimensions)?
we have to use formulas such as Perspective drawings or Fischer projections.
When considering the stereochemistry of cyclic compounds..?
we usually represent them as planar rings. That is the most symmetric (and highest in energy!) conformation. Such representations are called Haworth's Projections.
How do enantiomers only differ?
with respect to chirality
Do allenes have an axis of chirality
yes
Is a 180° rotation allowed transformation of a Fischer Projection Formula
yes
can biphenyl be chiral
yes due to restricted rotation about a single bond (atropisomerism)
Unlike enantiomers, which differ only with respect to the interaction with polarized light and other chiral materials, diastereomers
Isomers that have different chemical and physical properties. Therefore, a mixture of diastereomers is much easier to separate compared to a mixture of enantiomers.
What happens if an object that has a mirror plane through it?
It is superimposable on its mirror image and therefore non-chiral (achiral)
How many enantiomers may a living organism metabolize
Living organisms may metabolize only one enantiomer. Thus, when they are fed a racemic mixture, one enantiomer is digested while the other one is unaffected.
In the very first separation of a racemic mixture into enantiomers,
Louis Pasteur applied this method on racemic sodium ammonium salt of tartaric acid in 1848
What does an optically active material do?
Rotates the plane of polarized light
Why cant conformational isomers be separated or isolated?
They are readily interconverted into one another at a room temperature. For that reason, usually conformers are not considered to be true isomers
Why dont sp or sp2 hybridized atoms have a center of chirality?
They have a mirror plane
How do optical isomers differ?
With respect to their interaction of polarized light
Is an electron not at rest chiral?
Yes
Example of a chirality center
a carbon atom with four different substituents
Optical purity
a mixture is the ratio of its rotation to the rotation of a pure enantiomer expressed as a percent.
Enantiomeric excess
a mixture is the ratio of the amount of the excess of the predominant enantiomer over the minor one to the entire mixture.
When a racemic mixture is allowed to react with such chiral molecule (called the resolving agent)?
a pair of diastereomers is formed
Of the three symmetry elements which is the most difficult to identify?
alternate axis of symmetry because it is relatively rare
A number of naturally occurring molecules are?
available as pure single enantiomers
In a molecule that has two contiguous (neighboring) centers of chirality a meso form exists if?
both chirality centers have the same set of substituents.
What do Fischer projection formulas of compounds with more than one chirality center show?
compounds in their less stable, eclipsed, conformations
What are isomers that are related to each other as nonsuperimposable?
They are optical isomers or enantiomers. They exhibit a property called chirality
Enantiomeric excess formula
(p) - (Q) / (p) + (q) x 100% p and q are a pair of enantiomers
Symbols for a racemic mixture
(±) or (d,l
meso compounds
-Compounds that are achiral (non-chiral) and yet contain chirality centers -Molecules with multiple centers of chirality with a plane or a center of symmetry (that would be a horizontal plane of symmetry in a Fischer projection)
If the lowest priority group is on a horizontal bond, one or more of the allowed transformations should be performed on the Fischer formula:
-The exchange of the position of two substituents in pairs. The positions of both pairs must be exchanged simultaneously. Rotation by 180° also belongs to this category and therefore is an allowed transformation. The exchange in positions of only one pair of substituents will result in the enantiomer of the original molecule and, therefore, is not allowed. -The exchange of the positions of three substituents, clockwise or counterclockwise, while keeping the fourth substituent in its original position.
Not allowed transformation of the Fischer Projection Formula
-exchange of positions of a pair of substituents, and -rotation of the molecule by 90º.
A racemic mixture of a solid may have different melting point, or a different solubility compared to?
Pure enantiomers
Chromatographic Separation
1. A mixture to be separated is applied to a stationary phase and a mobile phase is allowed to flow past it. 2. Each component of the mixture adsorbs on the stationary phase and dissolves in the mobile phase to a different extent. 3. Compounds, which are adsorbed less tightly to the stationary phase and which are more soluble in the mobile phase, travel further than other components. We say that such compounds have lower retention times (are retained by the stationary phase for a shorter time). 4. In order to separate a racemic mixture into individual enantiomers, one has to use the stationary phase made of a chiral material. A chiral stationary phase interacts differently with each of the enantiomers. It forms stronger intermolecular interactions with one enantiomer than with the other one. Thus, the enantiomer that forms weaker interactions is eluted first, followed by the other enantiomer. Some of the chromatographic methods that are used to identify and separate enantiomers include column chromatography, thin layer chromatography, gas liquid chromatography (GLC) and high performance liquid chromatography (HPLC). Various carbohydrates, including paper (cellulose), are among the suitable chiral stationary phases.
A molecule has a nonsuperimposable mirror image if it lacks the following three elements of symmetry
1. Plane of symmetry 2. Center of symmetry 3. Alternate axis of symmetry
Three types of constitutional isomers
1. skeletal isomers 2. positional isomers (regioisomers) 3. functional isomers
Chromatography
A group of techniques based on the selective partitioning of material between two phases - a stationary phase (a liquid or a solid) and a mobile phase (a gas or a liquid
A molecule may have a maximum of how many stereoisomer
A molecule may have a maximum of 2n possible stereoisomers (including enantiomers and diasteriomers) where n is the number of chirality centers
Plane of Symmetry
A plane of symmetry reflects one half of the molecule into another. The two halves are mirror images of each other. For example, a compound with two identical substituents on a carbon atom, such as molecule of ethanol, has a plane of symmetry and is achiral.
An example of functional chirality?
A preference for using one hand over the other
What does a polarimeter contain?
A source of monochromatic (a single wavelength) ligh
What does an electron have?
A spin, which can be crudely described as the rotation of an elementary particle about its axis
erythro/threo isomerism
A type of isomerism that exist in compounds with two contiguous (neighboring) chirality centers
A wedge bond
Above the plane of the drawing
Cyclic compounds are more symmetrical than..?
Acyclic ones
In a chiral molecule..?
All the connectivities between the atoms are the same. However, the arrangement of atoms in space is different and the isomers cannot be interconverted by bond rotation.
Properties of racemic mixtures in a gas phase, a liquid phase and a solution are usually identical to those of?
Pure enantiomers
What are molecules that contain the central carbon bonded to a less than four different groups?
Archiral because they contain a plane of symmetry in the plane of the central carbon atom and two different substituents
When a molecule is achiral?
As long as at least one of its energetically accessible conformations has a mirror plane or symmetry, even if other more stable conformations lack such a plane. Such a symmetrical conformation does not have to be a stable, or a low energy, conformation
How are the shapes of isomers of chiral molecules related?
As two non-superimposable mirror images
What do optical isomers usually contain?
At least one carbon atom that is bonded to four different substituents. Since there is no plane of symmetry, such carbons are chirality centers
What may perspective drawing be applied to?
Both condensed structural formulas and line formulas
Conformational Isomers
Can be interconverted by bond rotation
Center of Symmetry
Center of symmetry is a point. A line drawn from an atom, or a group, through that point and extended an equal distance beyond it meets an identical atom, or a group. For example, the cyclic compound shown below is not chiral due to the presence of a center of symmetry.
What should one do when checking for whether a molecules is chiral?
Check for the possible presence of the three elements of symmetry
What are molecules that have a chirality center?
Chiral
What are chirality centers that overlap with atoms sometimes called?
Chiral atoms although an atom cannot be chiral or chiral center, asymmetric atoms, sterogenic centers, or stereocenters
Racemic mixture or racemate
Composed of equal amounts of the two enantiomers
Isomers
Compounds that have the same molecular formula but different structural formulas
Although the optical isomers may appear to be identical..?
They are non-superimposable mirror images of each other
What do perspective formulas make use of?
Dash and wedge bonds to indicate the spatial arrangement of atoms
Cahn-Ingold Prelog Convention
Developed to assign a designation to each enantiomer. The four different atoms bonded directly to the chirality center are assigned priorities based on a set of sequence rules for specifying configuration
What is another division of configurational isomers?
Enantiomers
What may chiral molecules be represented by?
Fischer Projection Formulas
Why are Fischer Projection Formulas useful?
For representing molecules with multiple centers of chirality. The chirality center is located at the intersection of horizantal and vertical bonds
What two classes do stereoisomers belong to?
Geometric Isomers and Optical Isomers
A dash bond indicates
Group that is below the plane
Stereoisomers
Have the atoms connected in the same way and therefore have the same structural formula but they differ in the positions of the atoms in space
Geometrical isomers (cis/trans)
Have the same formula and connections between atoms but have different three-dimensional structures because of the way that groups are attached to different sides of a double bond or a ring
Which energy conformation is more symmetrical?
High energy conformation is usually more symmetrical
Where else do meso forms exist?
In cyclic compounds
Difference between a racemic mixture and an achiral compound
Neither rotates the plane of polarized light - neither is optically active. However, a racemic mixture is composed of chiral molecules. It just happens that the two enantiomers are present in an equal amount and their rotations cancel out.
Are electrons with opposite spins chiral?
No
Are elementary particles such as electrons which are spheres chiral?
No
Are natural materials always enantiomers?
No
Is an electron at rest chiral?
No
Is a racemic mixture optically active?
No because it is composed of chiral molecules
Two enantiomers have same configurations?
No, they are different
Isomers of any type, including conformational isomers are ..?
Nonsuperimposable
Achiral
Objects identical to their mirror images
Chiral
Objects that are not identical to their mirror images
Optical isomerism
Occurs when a molecule is nonsuperimposable on its mirror image and always occurs in molecules that contain a chirality center
How can enantiomers be interconverted
Only by breaking covalent bonds
Does a sp3 hybridized atom have a 3-dimensional structure necessary to be the chirality center?
Provided that the four substituents are different
Disadvantages of biochemical resolution
Since one enantiomer is destroyed in the process, half of the starting material is lost. Furthermore, the enantiomer that is left may not be the desired one (often the biologically active enantiomer is the one that is desired). Usually, the living organisms that are employed are bacteria and, once suitable bacteria are found, the process may be highly efficient.
Stereochemistry
Study of the structure of molecules in three dimensions and the effect of that structure on the physical and chemical properties of molecules
Two molecules of any single compound are..?
Superimposable
absolute configuration or fischer convention
The convention was based on the configuration of glyceraldehydes as a standard. Rosanoff assigned to (+)-glyceraldehyde the Fischer projection in which the hydroxyl group was on the right (now it is called (R) configuration, or, according to the old nomenclature, D configuration) and the (-)-glyceraldehyde one with hydroxyl group on the left ((S) configuration, or L).
Some of the methods for the resolution of a racemate
The conversion to diastereomers and the separation of them, chromatographic separation, biochemical resolution and mechanical separation
What is the most common cause of chirality in an organic molecule?
The presence of a carbon atom bonded to four different substituents
resolution of a racemic mixture
The separation of a racemic mixture into individual enantiomers
Configuration
The three dimensional structure of a molecule
What is the ultimate test of whether two molecules which are mirror images of each other are enantiomers?
Their nonsuperimposability
Haworth's Projections
They allow us to easily determine if a cyclic compound contains a plane or a center of symmetry
Saying that two molecules are superimposable is the same as saying..?
They are identical
What are Fischer projections convenient for?
To represent molecules with more than one center of chirality
Enzymes and various receptors on surfaces of cells are chiral.
True
What are only configurational isomers usually considered to be?
True stereoisomers and sometimes the term stereoisomers applies to them only
How many isomers does a molecule with one chirality center have?
Two
How many possible spin orientations are there for an electron?
Two
What do chiral molecules have?
Two nonsuperimposable mirror images called enantiomers
When are Haworth projects suitable?
When chirality centers of a cyclic compound have the same set of substituents, one should check if the cis isomer is also the meso form of the compound
Two main types of isomers
constitutional isomers and stereoisomers
polarimeter
determines the extent and sign of rotation of an optically active material
Properties of racemic mixture are sometimes different than what?
different from those of the individual enantiomers
What is geometrical isomerism due to?
due to restricted rotation about a carbon-carbon bond (either a single, or a double bond).
Constitutional isomers
have the same molecular formula but the connections among their atoms are different
