Write the differences between the inductive effect and field effect.
- Inductive effect- particle effect, electron donation done through bond, pure displacement of shared electron pair in a carbon towards more electronegative atom or group through sigma bond.
- Field effect- cloud of negative charge, electron donation done through space, a polarization through space; drop off rapidly with the distance.
Five +I groups
1. (CH3)3C
2. (CH3)2CH
3. C2H5
4. CH3
5. O-
Five -I groups
1. NO2
2. CN
3. COOH
4. F
5. Cl
The inductive effect is a ___ effect, whereas the electromeric effect is a ___ effect.
- permanent
- temporary
Electromeric effect is seen in ___ pi system whereas resonance effect predominates in ___ pi system.
- unconjugated
- conjugated
Hyperconjugation is also known as no ___ resonance.
Bond
+E groups
- Addition of H+ to alkene
- Addition of HBr to an alkene
- E groups
- Addition of cyanide ion (CN-) to the carbonyl group
- Addition of hydroxide (OH-) to amide carbonyl
Arrange the relative strength of the following factors on a molecule's acidity (structural effects).
1. Resonance
2. Atomic radius
3. Electronegativity
4. Inductive effect
The formal charge on nitrogen and oxygen in NO+ is
0 and +1
Addition reaction
- Atoms are added to double or triple bonds
- Alkene or alkyne undergoes addition reaction to break a double or triple bond
- Two reactants make one product
Substitution reaction
- A hydrogen atom or functional group is replaced by a different atom or functional group
- Two reactants make two products
Elimination reaction
- Atoms are removed from a molecule to form double or triple bonds
- Reverse of addition
- One reactant breaks into two products
Rearrangement reaction (not in syllabus)
- Number of atoms are same, just change in position/attachment takes place
- Reverse of addition
- No byproduct formed
- One reactant forms one product
Oxidation and reduction reactions
- Change in the number of H and O atoms bonded to C
- Always occur together
- One reactant is oxidized whereas the other is reduced
Homolysis
- If a covalent single bond is broken so that one electron of the shared pair remains with each fragment
- Radicals
Heterloysis
- If the bond breaks with both electrons of the shared pair remaining with one fragment
- Ions
Non-superimposable stereoisomers, which are mirror images of each other, are known as ___
Enantiomers
Non-superimposable stereoisomers that are not mirror images of each other are known as ___
Diastereosiomers
Diastereoisomers are possible only when the molecule contains more than ___ chiral center
One
E/Z alkene isomers are known as
Geometric isomers (diastereomers)
The structure of the molecule, (Z)-3-ethyl-2-pentene-4-yne, is
Cis
Molecules or objects that possess a mirror plane of symmetry, are superimposable on their mirror image, are termed
Achiral
A molecule containing carbon with four different groups results in a ___ molecule, and the carbon is referred to as a ___ center.
- chiral
- chiral, asymmetric, stereogenic
Molecules enriched in an enantiomer will rotate plane-polarized light and are said to be ___ active.
optically
The optical rotation depends upon the substance, concentration, path length through the sample, and ___ of light.
wavelength
A polarimeter measures the rotation of ___ light that has passed through a solution.
plane-polarized
Plane polarized light is the light that oscillates in only one plane; when it passes through, the solution of an achiral compound remains in that plane, and the optical rotation is ___.
0, optically inactive
Solutions of chiral compounds rotate plane-polarized light, and the molecules are said to be ___ active.
optically
Enantiomers will rotate plane-polarized light of the same magnitude but in ___ directions.
opposite
The specific rotation is a ___ of a chiral molecule.
physical constant
If ___ exists between two chiral conformers, the molecule is not chiral.
equilibirum
The maximum number of possible stereoisomers of D-(+)-glucose is ___.
16
Maximum number of possible stereoisomers and stereocenters of cholesterol is ___ and ___.
8 stereocenters and 256 stereoisomers
What do you mean by optical resolution and racemate?
- Optical resolution- the process followed to separate the two enantiomers from a racemic mixture into pure enantiomers by temporarily converting them into diastereomers.
- Racemate/racemic mixture- the 50:50 mixture of enantiomers denotaed by (+-)
A molecule that is ___ but that can become chiral by a ___ alteration is a prochiral molecule.
- achiral
- single
Re and Si are used to describe the ___ of the ___ sp2 reactant.
- faces
- prochiral
The ___ of chemical bonds never releases energy to the external environment. Energy is only released when chemical bonds are ___.
- breaking
- formed
A 1.00gm sample is dissolved in 20.0mL ethanol. 5.00mL of this solution is placed in a 20.0cm polarimeter tube at 20°C. The observed rotation is 1.25° counterclockwise. Calculate the specific rotation of the molecule.
alpha/(l)(c)
1.25/2(1/20) = 12.5
What do you mean by specific rotation?
Specific rotation is a standardized value for the optical rotation. It is a physical constant of a chiral molecule. Specific rotation is the same but optical rotation may be different. Measured with alpha (optical rotation in degrees), l (path length in dm), and c (concentration of sample in g/100mL).
Define optical purity.
Optical purity is enantiomeric excess which is where there is more of either the (R)-enantiomer or the (S)-enantiomer. This is because chiral molecules cause the rotation of plane-polarized light and are said to be optically active.
The specific rotation of (S)-2-iodobutane is +15.90°. Determine the % composition of a mixture of (R)- and (S)-2-idobutane if the specific rotation of the mixture is -3.18°.
Optical purity= observed rotation/rotation of pure enantiomer * 100
-3.18/-15.90 = 20%
Percentage needs to be positive so the rotation of the enantiomer got flipped, can't flip observed rotation because that one matters).
The label of a chemical bottle says that the bottle contains 98% ee (S)-conformer— what does it mean?
ee is the enantiomeric excess which is the difference between the mole fraction of each enantiomer. 98% ee S=
S= 98% +2/2, so S= 99% and R= 1%
What is the difference between absolute configuration and relative configuration?
- Absolute configuration- the precise three-dimensional arrangement of atoms in space.
- Relative configuration- compares the three-dimensional arrangement of atoms in space of one compound with those of another compound.
There's no correlation between the sign of the optical rotation and three-dimensional arrangement of atoms.
Write and explain the Cahn-Ingold-Prelog rules of priority determination.
- Assign a priority number to each group attached to the chiral carbon (number is from 1-4, not the same format as IUPAC priority).
- Atom with the highest atomic number is assigned the highest priority #1
- In case of ties look at the atomic weights (isotopes, seen in hydrogen)
- In case of ties look at the next atoms along the chain (O can be alone and it will still be high priority if it is the highest atomic number and it has another atom bonded to it)
- Double and triple bonds are treated like bonds to duplicate atoms (for instance, if there is a carbonyl it will now be a carbon bonded to two oxygens giving it priority over CH3)
What do you mean by Cahn-Ingold-Prelog R-S notational system?
- Use the Cahn-Ingold-Prelog priority rules to assign priority (1-4) to the four different groups of the chiral carbon.
- Orient the molecule so that the lowest priority atom is in the back. Look at the remaining three groups of priority 1-3. If the remaining three groups are arranged so that the priorities 1->2->3 are in a clockwise fashion, then assign the chiral center as R, rectus to the right. If the remaining groups are arranged 1->2->3 in a counterclockwise manner, then assign the chiral center as S for sinister.
If molecules have (R) configuration then they rotate plane polarized light to the right. If molecules have (S) configuration then they rotate plane polarized to the left.
- Hand rule. Orient the lowest priority group up. Point your thumb in the direction of the lowest priority group. If you need to use your right hand so that your fingers point in the direction of the group priorities in the order 1->2->3, then the stereogenic center is assigned R. If your left hand is required so that your fingers point in the direction of the group priorities 1->2->3, the stereogenic center is assigned S.
Discuss unfamiliar chirality with examples from biphenyl and allene (one each).
Unfamiliar chirality is chirality as a whole without having a chiral center.
- Allene- no plane of symmetry, still capable of deflecting plane-polarized light so it's chiral.
- Biphenyl- perpendicular to each other so there's no plane of symmetry. If the group is bigger, rotation is restricted. Still shows chirality.
What do you mean by pro-R and pro-S?
An sp3 carbon with two of the same groups is considered prochiral. The identical groups are distinguished by considering either and seeing if it was increased in priority in comparison with the center. Here, you are looking at the molecule from the top and from the bottom. It will be pro-R if the order of priority is going to the right and pro-S if the priority is going to the left.
It will be inversed if looking from the bottom plane.
What do you mean by eutomer and distomer?
- Eutomer- the enantiomer of a chiral drug possessing therapeutic activity of interest (bioactive enantiomer).
- Distomer- enantiomer with lower affinity or less activity or nonactivity -> can be toxic.
What is eudismic (eudysmic) ratio?
It measures the pharmacological potency ratio of the eutomer to the distomer, or the stereoactivity of a chiral drug.
Explain with appropriate examples thermodynamic control and kinetic control.
In a chemical reaction they can decide the composition in a reaction
product mixture when competing pathways lead to
different
products and the reaction conditions influence the selectivity.
- The distinction is relevant when product A forms faster than product B because the activation for product A is lower than that for product B, yet product B is more stable. In such a case, A is the kinetic product and is favored under kinetic control and B is the thermodynamic product and is favored under thermodynamic control.
Homolysis and heterolysis
- Homolysis- if a covalent single bond is broken so that one electron of the shared pair remains with each fragment. Always produces radicals.
- Heterolysis- if the bond breaks with both electrons of the shared pair remaining with one fragment. Always produces ions.
Electrophile and nucleophile
- Electrophile- an electron deficient atom, ion, or molecule that has an affinity for an electron pair, and will bond to a base or nucleophile. Ex: H3O+, NO2+, HCl, HBr, HI
- Nucleophile- an atom, ion, or molecule that has an electron pair that may be donated in bonding to an electrophile. Ex: H2O, OH-, NH3, Cl, CN
How many types of electrophiles and nucleophiles are possible? Give one example for each type.
- Electrophiles: 3 types
1. Positive charge- cations or free radicals seeking electron-rich entrees. Ex: SO3H+
2. Neutral species having incomplete octet, has no formal charge. Possesses an empty orbital to receive the electron pair. Ex: BH3, BCl
3. Strong dipole moment. Ex: HFl, HCl
Nucleophiles: 2 types
1. Uncharged/nucleophilic nucleophile. Ex: NH3, H2O, R-OH,
2. Anionic nucleophile- species with a negative charge because it has lone pairs of electrons. Ex: OH-, NH2-, CH3-
Calculate the formal charge (FC) on nitrogen and boron atom in H3N-BH3.
Number of valence electrons - (e in lone pairs + # of bonds)
N: 5 - (0+4) = +1
B: 3 - (0+4) = -1
What is chiral resolution? Write different methods of chiral resolution.
- Isolation of two enantiomers in pure form from racemic mixture. You separate the R and the S.
- This process involves reacting the racemic mixture with a different chiral molecule and thereby producing two different diastereomers.
Inductive effect
- Permanent displacement of shared electron pair in a carbon towards more electronegative atom or group, through sigma bond.
-I effect
Electron withdrawing, electronegative atom is attached to the terminal of the carbon chain in a compound, the electrons are displaced in the direction of the attached atom.
Ex: -NO2 > CN > -COOH > F > Cl > Br > I > OH > C6H5 > H
(positive dipole moment) C -->-- F (negative dipole moment)
+I effect
Electron donating, electropositive (less electronegative) atom is attached to the terminal of the carbon chain in a compound, the electrons are displace in the direction of the attached atom.
Ex: (CH3)3C- > (CH3)2CH- > -C2H5 > -CH3
(negative dipole moment) C --<-- CH3 (positive dipole moment)
Field effect
A polarization through space; drop off rapidly with the distance. In most cases, inductive and field effects operate together and difficult to separate them.
Field effect, electron donating group, +I
O-, COO-, CR3, CHR2, CH3
Field effect, electron withdrawing group, -I
NR3+, SR2+, NH3+, NO2, COOR, CO2, CN, SO2
Electromeric effect
The complete transfer of electrons of a multiple bond towards one of the bonded atoms at the demand of an attacking reagent. The electromeric shift of electrons takes place only at the moment of reaction. Show by compounds containing multiple bond and is a purely temporary effect.
+E
When the electron pair moves toward the attacking reagent. Addition of acids to alkenes is an example. After the transfer, the reagent gets attached to the atom where the electrons have been transferred to.
Ex: addition of acid to alkene (look at notes).
-E
When the electron pair moves away from the attacking reagent.
Ex: addition of cyanide ion (CN-) to the carbonyl group (look at notes).
Mesomeric/resonance effect
The flow of electrons from one part of a conjugated pi system to the other.
-M/-R
When the electron displacement is towards the group (EWG).
Ex: -NO2, -CHO (look at notes).
+M/+R
When the electron displacement is away from the group (EDG).
Ex: -OH, -OR, -Cl (look at notes).
I-strain
- Internal strain.
- Involves in deforming bond and torsional angles away from more stable geometry.
- Involved in deforming bond and torsional angles away from more stable local geometries.
B-strain
- Back/bulky strain, bulky groups attacking.
- Strain caused by steric repulsion.
- Involves direct steric clashes that occur on adduct formation.
F-strain
- Steric hindrance, front/face strain.
- Bulky groups make it difficult for the Lewis acid and Lewis base centers to approach and interact.
Hyperconjugation
The stabilizing interaction that results from the interaction of the electrons in a sigma bond with an adjacent empty or partially filled p orbital to give an extended molecular orbital that increases the stability of the system. The higher the number of hyperconjugative structures, the higher the stability of the system.
How can you classify the major reactive intermediates in organic chemistry?
1. Electrophile- an electron deficient atom, ion, or molecule that has an affinity for an electron pair, and will bond to a base or nucleophile. Carbocations. Ex: H3O+, HCl, NO2+, SO3.
2. Nucleophile- an atom, ion, or molecule that has an electron pair that may be donated in bonding to an electrophile. Carbanion. Ex: I-, Cl-, OH-, CN-
3. Free radicals- radical intermediates. Carbon radicals have only seven valance electrons, and may be considered electron deficient, however, they do not in general bond to nucleophile electron pairs, so their chemistry exhibits unique differences from that of conventional electrophiles. Ex: O2*-, OH*, NO*, NO2*