orgo uW: Compounds & Reactions Flashcards
Carbocations
Carnoanions
SN1 Reaction
- SN1 reactions are nucleophilic substitutions that occur in two steps:
- Formation of a carbocation (loss of LG)
- Nucleophilic attack of the carbocation
Reactivity of alkyl halide substrates depends on the alkyl halides’ substitution. Tertiary alkyl halides are the fastest to react because they form a stable carbocation; as substitution decreases, the alkyl halide will react more slowly because it forms a less stable carbocation.
Solvolysis Reaction
Primary, secondary, & tertiary leaving groups: draw them
R & S Forms
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The R or S configuration of a chiral carbon depends on the spatial arrangement of its substituents.
- higher priority is give to greater atomic number (if there is a tie, the atomic numbers of the next attached atoms are considered)
- When the lowest-priority group is pointed into the plane (dash), the chiral carbon is R if priorities 1-2-3 are arranged in a clockwise fashion and S if they are counterclockwise.
- When the lowest-priority group is pointed out of the plane (wedge), the chiral carbon is S if priorities 1-2-3 are arranged in a clockwise fashion and R if they are counterclockwise
E & Z forms
- Alkenes are geometric isomers that differ in the substituent arrangement about a double bond and can be classified as either E or Z.
- Z alkene=highest priority groups on same side (top or bottom) of double bond
- E alkene=highest priority groups on opposite side of double bond
SN2 Reaction
- SN2 reaction is a concerted substitution reaction where a nucleophile forms a bond with an electrophile while a leaving group is displaced (in one step)
- If the electrophile is a chiral center, its stereochemistry will be inverted in the product.
- Therefore, if the electrophilic carbon has an R configuration, it will adopt an S configuration after the reaction and vice versa, provided the priority ranking of the nucleophile is the same as the leaving group.
Isomers
Priority Rules for E/Z determination
Priority Rules for R/S determination
Stereospecifity for SN1 & SN2
- Stereospecific reactions occur when stereoisomers undergo the same reaction and give different stereoisomers of the product ( 2 configuration of a chiral center)
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Tertiary alkyl halides readily undergo SN1 reactions, which are not stereospecific because the nucleophile can attack the planar carbocation intermediate from the top or the bottom of the carbocation, forming two stereoisomers.
- attacks, LG leaves and then Nu adds to top or bottom
- 2 products
- tertiary carbons form a more stable carbocation
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Primary alkyl halides readily undergo SN2 reactions, which are stereospecific because the nucleophile attacks from the opposite side, where the leaving group is eliminated (backside attack) causing inversion at the elecrophilic carbon
- one product
Steric Hinderance
Distilation
When temp is increased quickly:
When temp is increased slowly:
- The mixture must be heated slowly to ensure that a lower boiling–point compound evaporates before a higher boiling–point compound and that the molecules are separated.
- impurites=heated too quickly, causing molecules to evaporate together
Fractional distilation
- uses a column to imrpove seperation of compounds by increasing the lenght of the path the vapor must travel before condensing & dripping into the recieving flask
What are boiling chips used for?
- Boiling chips are used to evenly heat a liquid and prevent superheating.
- Their use in the distillation would prevent the mixture from abruptly forming large bubbles that could spill over into the receiving flask.
Simple & fractional distillation are done at what pressure?
- simple distilations are done at atmospheric pressure
- vacuum distilations are done at reduced pressure, decreasing the compound’s boiling point relative to the boiling point at atmospheric pressure
Gas Liquid chromatography
- is a technique that separates compounds in a mixture based on boiling point.
- The mobile phase is an inert gas, and the stationary phase is a liquid that coats the column, which is in a heated oven.
- The molecule with the lowest boiling point will reach the detector before molecules with higher boiling points.
Boiling point & branching
Organic compounds boiling points
Ultraviolet (UV) Light
- is electromagnetic radiation that corresponds to wavelengths between 200 nm and 400 nm, and UV absorption causes an electron transition from the ground state to a higher energy level.
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In the ground state, π electrons from double bonds are in the π bonding molecular orbital, and nonbonding electrons are in the n nonbonding molecular orbital.
- These electrons can be excited to the π* antibonding orbital.
Draw electromagnetic spectrum
high-performance liquid chromatography (HPLC)
- In high-performance liquid chromatography (HPLC), two types of columns—normal-phase (NP) and reverse-phase (RP)—can be used, depending on the polarity of the compounds being separated.
- NP-HPLC (normal) consists of a polar stationary phase and a nonpolar mobile phase (nonpolar compounds elute before polar compounds)
- RP-HPLC (reverse) consists of a nonpolar stationary phase and a polar mobile phase.
- Molecules with similar polarity to the stationary phase interact with it more and have longer retention times.
Reverse-Phase HPLC
Normal-phase HPLC
- HPLC Example: A mixture containing an ester, a carboxylic acid, an alcohol, and an alkane separated by NP-HPLC elutes in the following order:
- alkane, ester, alcohol, and carboxylic acid
- peak III (second-longest retention time)=alcohol
Example of conformational isomers
- are structures that have the same formula and connectivity, and can be interconverted by the rotation of σ bonds.
- Because conformational isomers are identical except for structural bond rotations, they are the same compound.
Chair conformations
Quatorial & axial projections
Example of trans isomer
Enantiomers Exampe
Diastereomers Example
Constitutional isomers
Calculate the number of steroisomers that exist in the compud below:
- The maximum number of stereoisomers possible for a compound is determined by the expression 2n, where n is the number of stereocenters.
- However, the actual number of stereoisomers for a particular compound could be less than 2n if two of the possible stereochemical configurations have an internal mirror plane of symmetry (meso compound), making them conformations of the same compound.
the experimental data obtained when a chiral molecule interacts with plane-polarized light is called:
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the specific rotation
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Specific rotation measures the direction (+:clockwise or −: counterclockwise) and magnitude (angle) of rotation by which chiral molecules rotate plane-polarized light. This value is a physical characteristic of chiral molecules, is unique for each molecule, and must be determined experimentally.
- a polarimeter is the instrument used to measure the rotation of polarized light
- enantiomers have specific rotaions of equal magnitude but in opposite directions
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Specific rotation measures the direction (+:clockwise or −: counterclockwise) and magnitude (angle) of rotation by which chiral molecules rotate plane-polarized light. This value is a physical characteristic of chiral molecules, is unique for each molecule, and must be determined experimentally.
Suppose that a 0.2 g/mL solution of (S)-ibuprofen in a 2 dm long cell rotates plane-polarized light +10°. What is the specific rotation for (S)-ibuprofen?
- Specific rotation is the angle by which chiral molecules rotate plane-polarized light and contains direction (+ or −) and magnitude (degrees).
- see answer and calculation in image & equation
Two separate reactions are conducted in which a compound containing a ketone, an ester, and a carboxylic acid is reacted with borane (BH3) in THF in one reaction and with NaBH4 in methanol in the other. Which of the following explains why different products are observed?
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Answer: BH3 will selectively reduce carboxylic acids, & NaBH4 will selectively reduce ketones
- carboxylic acids can be selectively reduced to primary alcohols by the reducing agent BH3
- carboxylic acids cannot be reduced by NaBH4, which is selective for the reactive carbonyl ketones & aldehydes
SN2 & leaving groups
- SN2 reactions occur when a nucleophile donates electrons to an electrophile & the electrophile loses a leaving group
- Good leaving groups must be able to stably carry the electrons they recieve
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Halogens are generally good leaving groups & large halogens are better leaving groups than small halogens (I is a better leaving group than F)
- halogens are good leaving groups because they form stable anions
Steric Hinderance
- Sterically hindered chemical groups are physically inhibited from interacting with other molecules.
- For this reason, they are less capable of acting as nucleophiles in SN2 reactions.
- Tertiary alcohols are more sterically hindered than secondary alcohols, which are more sterically hindered than primary alcohols.
- primary alcohols are more acidic
Acids help catalyze the Fischer esterification by doing all of the following:
- Acids can catalyze many reactions by donating protons to a reactant, generating an increased positive charge.
- This creates enhanced electrophiles such as carbocations and increases the stability of leaving groups. Acids generally decrease nucleophilicity of the molecules to which they donate protons.
Experimental controls
- Experimental controls, including positive and negative controls, are required to demonstrate the validity of a test result.
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Positive controls show what the maximum effect would look like, and negative controls show what no effect would look like.
- Both must relate to the dependent variable being measured without influence from the independent variable.
Nucleophilicity trend
acids strength & pKa
- When comparing the nucleophilicity of atoms of equal negative charge, nucleophilicity tends to increase from right to left across a row of the periodic table as electronegativity decreases.
- Atoms of higher electronegativity more effectively stabilize negative charge and less readily donate electron density to electrophiles whereas those of lower electronegativity stabilize a negative charge less effectively and more readily donate electrons to electrophiles.
- weak acids (high pKa) produce strong conjugate bases (and vice versa), & strong bases (low pKb) tend to be strong nucleophiles
Decreasing steric hinderance, does what to nucleophilicity?
INCREASES NUCLEOPHILICITY
Inductive Effect
- The inductive effect occurs when electron density is donated through sigma bonds.
- Carbocations are stabilized by electron donating groups because they donate electrons to the positively charged carbon; they are destabilized by electron withdrawing groups because they pull electrons away from the carbocation, creating two adjacent positive charges.
Steric Hinderance
- The steric hindrance of a substrate must be considered when determining whether it can undergo a particular reaction.
- The extent of a substrate’s steric hindrance can dictate which nucleophilic substitution (SN1 or SN2) it is likely to undergo.
- SN1 reactions permit sterically hindered electrophiles whereas SN2 reactions require easily accessible electrophiles.
Examples of E/Z & cis/trans classification
E/Z double bonds classification
Cis/trans classification
(S,R)- and (R,R)-labetalol, the active forms of the drug, can be described as?
- Diasteromers
- are stereoisomers that are not mirror images. They contain at least two stereocenters in which one or more, but not all, are in opposite configurations.
an entaiomer will be (S,R) (R,S)
Effect of enantiomers on polarized light
- Enantiomers rotate plane-polarized light by the same magnitude in opposite directions.
- No correlation exists between diastereomers and the magnitude or direction of rotation.
- Racemic mixtures have a rotation of zero because they consist of equal amounts of each enantiomer.
A structural isomer, or constitutional isomer:
- is a molecule that contains the same molecular formula as another molecule.
- The atoms in each molecule differ in their connectivity.
R/S examples:
which molecule is equivalent to this one in the image?
- the answer can be rotated 90 degrees to the left to put the subsituents in the same position as compound 1
- Chiral compounds with the same four substituents on the central carbon are identical if they have the same stereochemical configuration.
- When the lowest-priority substituent is pointing away from the viewer, an R configuration is present if the substituent priorities follow a clockwise progression, whereas a counterclockwise progression indicates an S configuration.
- If the lowest-priority substituent is pointing toward the viewer, an R configuration is indicated by substituent priorities following a counterclockwise progression.
Enantiomer example
what can we say about structural isomers under thermodynamic conditions when product 1 (is more stable) than product 2?
- there is a greater amount of compound 1 in the mixture
- because the reaction was performed under thermodynamic conditions, the more stable isomer will be the major product
- compound 1 is more stable becuase it contains a more substituted double bond than compound 2
Isomers
- are different compounds with the same molecular formula, and some reactions produce a mixture of isomers
- the major product of a reaction is dependent on the reaction conditions: the more stable product will predominate under thermodynamic conditions, & the less stable product will predominate under kinetic conditions
constituational isomers
Diasteromers
Enantiomers
Cis-trans isomers
Thermodynamics & kinetic enolates:
molecules must have all subsituents in the same relative position & seterochemical orientation to be considered the same molecule
what molecules are the same like the one in the image?
redraw compound one in a chair confirmation:
Hydroquinone structure
Vit K 2,3-epoxide
going from hyrdoquinone to 2,3-epoxide, a carobonyl is formed, what can we say about the one carbonyl group is formed?
- overlapping p orbitals
- During Reaction 1, the two hydroxyl groups (–OH) covalently bonded to the carbon ring are converted to carbonyl groups (C=O).
- Each of the original single bonds consisted of one sigma bond between two covalently bonded atoms whereas the newly created double bonds contain a sigma bond and a pi bond made from overlapping p orbitals.
- A pi bond is created by side-by-side overlap of p orbitals whereas a sigma bond is formed by direct end-to-end overlap of atomic orbitals. A _single bond_ contains one sigma bond; a _double bond_ contains one pi bond and one sigma bond. A _triple bond_ contains two pi bonds and one sigma bond.
Hybrid orbital theory
- combines bound atomic orbitals into mixed hybrid orbitals of equivalent energy & shape
- to determine an atom’s hybridization, count the number of lone electron pairs & sigma bonds
- the resulting number corresponds with the number of hybrid orbitals or electron domains
Proton (1H) nuclear magnetic resonance (NMR)
- examines the spin properties of hydrogen nuclei as measured by chemical shifts to determine molecular structure.
- Protons shielded by nearby electrons have smaller chemical shifts (upfield).
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Deshielded protons, such as those near electronegative atoms, have larger chemical shifts (downfield).
- as hydrogen bonding increases, the proton becomes more deshielded & is found downfield
Retention time & HPLC
- HPLC
- mobile phase: hexane
- stationary phase: silica
- longer retention time=lower mobile phase affinity & higher stationary phase affinity
Valence Shell Electron Pair Repulsion (VSEPR)
What are the bond angles of the water molecule formed during Reaction 1, the methylated carbon atom of the product from Reaction 1, and the alkene formed in Reaction 2, respectively?
- Answer: 104.5, 109.5, & 120
- Valence shell electron pair repulsion theorizes that atoms within a molecule strive to achieve a geometry that minimizes electron repulsion.
- Hybridization of sp, sp2, and sp3 correlates with 180°, 120°, and 109.5° bond angles, respectively.
- Despite the water molecule’s sp3 hybridization, it displays a bond angle of 104.5° due to lone electron pair repulsion.
What is the original amino acid here?
