Organic Chemistry- Analyzing Organic Reactions Flashcards
In an acid-base reaction, what happens?
An acid and base react, resulting in the formation of the conjugagate base of the acid and the conjugate acid of the base.
The acid base reaction procees as long as what?
The reactants are more reactive, or stronger, than the products that they form
The lewis acid/base defintion concerns itself with what?
Transfer of electrons in the formation of coordinate covalent bands.
The bronsted-lowry definition of acid/base concerns itself with what?
Proton transfer
What is a Lewis acid?
An electron acceptor in the formation of a covalent bond
Lewis acids tend to be _____ and have ____
Electrophiles
They have vacant p-orbitals into which they can accept an electron pair, or are positively polarized atoms.
What is a Lewis base?
An electron donor in the formation of covalent bonds
Lewis bases tend to be _____ and have _____.
Nucleophiles.
They have a lone pair of electrons that can be donated, and are often anions carrying a negative charge.
When Lewis acids and bases interact, they form what?
Coordinate covalent bonds
What are coordinate covalent bonds?
Both electrons in the bond came from the same starting atom (the Lewis base)
What is the Bronsted-Lowry definition of an acid and base?
An acid is a species that can donate a proton (H+)
A base is a species that can a ccept a proton
Water is ______ which means it has the ability to what?
Amphhoteric
The ability to act as either Bronsted-Lowry acids or bases
Water can only act like a base in _____, and can only act like an acid in _______.
Act as a base in acidic solutions
And acid in basic solutions
What are other examples of amphoteric molecules?
Al(OH)3
HCO3-
HSO4-
What is the acid dissociation constant?
Ka, measures the strength of an acid in solution
What equation is used to determine the acid dissocation constant of acid HA
HA H+ + A-
Ka = [H+][A-]/[HA]
How do you find the pKa of an acid HA?
pKa = -logKa
More acidic molecules will have _______ pKa, more basic molecules will have a __________ pKa
Smaller (or negative) pKa
Larger (positive) pKa
Acids with a pKa below -2 are considered what?
Strong acids, which alwmost always dissociates completely in aqueaous solution
Weak organic acids often have pKa values between _____ and _____pKa
-2 and 20
What is the pKa of Alkane?
-50
What is the pKa of alkene?
-43
What is the pKa of hydrogen?
42
What is the pKa of amine?
-35
What is the pKa of alkyne?
25
What is the pKa of Ester?
25
What is the pKa of ketone/aldehyde?
20-24
What is the pKa of alcohol?
17
What is the pKa of water?
16
What is the pKa of carboxylic acid?
4
What is the pKa of hydronium ion?
-1.7
Bond strength _____ down a periodic table?
Decreases
Acidity _____ down a periodic table?
increases
The more electronegative an atom, the higher _______.
The Acidity
When electronegativity and bond strength oppose each other; to determine acidity, which takes precedence?
Low bond strength takes precedence
What are alpha-hydrogens?
Hydrogens connected to the alpha-carbon
What are alpha-carbons?
A carbon adjacent to the carbonyl
Why are the alpha-hydrogens in a carbonyl compound easily lost?
Because the enol form of carbonyl-containing carbonions is stabilizd by resonance, these are acidic hydrogens that are easily lost.
What are functional groups that act as acids?
Alcohols, aldehydes, ketones (at the alpha-carbon) Carboxylic acids Most carboxylic acid derivatives.
The functional groups, that arc as acids, are easier to target with what? Why?
Basic (or nucleophilic reactants) because they readily accept a lone pair
What functional groups act as bases?
Amines and Amides
Amines and Amides will be seen in what bonds?
Peptide bonds.
The nitrogen atom of an amine can form coordinate covalent bonds by donating a lone pair to a Lewis acid
What are the two groups of reactions in organic chemistry?
Oxidation-Reduction
Nucleophile-electrophile
What is important to the reactions of alcohols and carbonyl-containing compounds?
Nucleophiles
electrophiles
Leaving groups
What is the definition of nucleophiles?
Nucleus-loving species with either lone pairs or pi bonds that can form new bonds to electrophiles.
What is the distinction between nucleophiles and bases?
Nucleophile strength is based on relative rates of reaction with a common electrophile– and therefore a kinetic property. Base strength is related to the equilibirum postion of a reaction– and therefore a thermodynamic property.
What are some common examples of nucleophiles?
Anions
pi bonds
Atoms with lone pairs
On test day, what should you look for to identify nucleophiles?
Carbon, hydrogen, oxygen or nitrogen (CHON) with a minus sign or lone pair to identify them.
As long as the nucleophilic atom is the same, the more basic the nucleophile, the more ________.
Reactive it is
Comparing atoms in the same row of the periodic talbe, the more _______ the more _______.
The more basic
The more Reactive
Is the reactivity of a nucleophile the same down a column as a row on the periodic table?
No
What are the 4 factors that determine nucleophilicity?
Charge
Electronegativity
Steric hinderance
Solvent
Nucleophilicity increase with what?
Increasing electron density (more negative charge)
Decreasing electronegativity
Less bulky molecules
Non protic solvents
Nucleophilicity decreeases with what?
Decreasing electron density
Increasing electronegativity
Bulky molecules
Protic solvents by protonating the nucleophile or through hydrogen bonding
In polar protic solvents, nucleophiliciy increases _______ the periodic table.
Down the periodic table
In polar aprotic solvents, nucleophilicity increases ____________ the periodic table.
Up
What are common protic solvents?
Carboxylic acid
Ammonia/Amines
Water/alcohol
What are common aprotic solvents?
Dimethylformamide (DMF)
Dimethylsulfoxide (DMSO)
Acetone
What are good examples of the effect of solvent on nucleophilicity?
The halogens
In protic solvents, halogens nucleophilicity decreases in what order?
I- > Br- > Cl- > F-
In protic solvents, why do halogen’s nucleophilicity decrease in the order I- > Br- > Cl- > F- ?
The protons in solution will be attracted to the nucleophile. F- is the conjugate base of HF, a weak acid. As such, it will form bonds with the protons in solution and be less able to access the electrophile to react. I-, on the other hand, is the conjugate base of HI, a strong acid. As such, it is less affected by the protons in solution and can react with the electrophile.
In aprotic solvents, halogen’s nucleophilicity will decrease in what order?
F- > Br- > Cl- > I-
In aprotic solvents, why do halogen’s nucleophilicty decrease in the order F- > Br- > Cl- > I- ?
There are no protons to get in the way of the attacking nucleophile. In aprotic solvents, nucleophilicty relates directly to basicity.
What don’t you want to use for nucleophilic /electrophilic reactions? Why?
Nonpolar solvents because we need our nucleophile to dissolve. Charged molecules are polar by nature, polar solvent is required to dissolved the nucleophile as well as because like dissolves like.
What are examples of strong nucleophiles?
HO- RO- CN- N3- NH3 RCO2-
What are examples of weak or very weak nucleophiles?
H2O
ROH
RCOOH
How are electrophiles defined?
Electron loving species with a positive charge or positively polarized atom that accepts an electron pair when forming new bonds with nucleophiles.
What is the distinct difference between electrophiles and Lewis acids?
That electrophilicity is a kinetic property
Acidity is a thermodynamic property
Electrophiles will almost always act as what?
Lewis acids
What increase electrophilicity?
A greater degree of positive charge
A _____ is more electrophilic than a _______.
Carbocation
Carbonyl carbon
What influences the electrophilicity in a species without empty orbitals?
The nature of the leaving group
Better leaving groups in species without empty orbitals makes what more likely in regards to electrophilicity?
A reaction will happen
If empty orbitals are present in electrophiles, what can happen?
An incoming nucelophile can make a bond with the electrophile without displacing the leaving group
What are identical properties when it comes reactivity?
Electrophilicity and Acidity
What molecules act like acids, and thus act like electrophiles? What might target them?
Alcohols
Aldehydes and ketones
carboxylic acids and their derivatives
Nucleophilic attack
What are often ranked by electrophilicity?
The carboxylic acid derivatives
Out of the carboxylic acid, ester, anhydrides and Amids; List them in order from most reactive to least.
Anhydrides
Carboxylic acids and esters
Amides
Derivatives of higher reactivity can form _____, but not _______.
Derivatives of lower reactivity, but not vice-versa
What are leaving groups?
The molecular fragments that retain the electrons after heterolysis.
What are heterolytic reactions?
The opposite of coordinate covalent bond formation; a bond is broken and both electrons are given to one of the two products.
The best leaving groups will be able to what? What are examples of good leaving groups?
Stabilize the extra electrons. Weak bases are more stable with an extra set of electrons and therefore make good leaving groups.
(I-, Br-, and Cl-)
Leaving groups ability can be augmented by what?
Resonance and by inductive effects from electron-withdrawing groups: These help delocalize and stabilize negative charge
What will almost never serve as a leaving group?
Alkanes and hydrogen ions Because they form very reactive, stronly basic anions
How should leaving groups and nucleophiles be looked at?
They are serving opposite functions. In substition reactions, the weaker base (The leaving group) is replaced by the stronger base (the nucleophile)
What are the two types of nucleophilic substitutions reactions?
Sn1
Sn2
What are nucleophilic substitution reactions?
a nucleophile forms a bond with a substrate carbon and leaving group leaves.
What is the full name of an Sn1 reaction?
Unimolecular nucleophilic substition reaction
What are the two steps of a Sn1 reaction?
The rate-limiting step
Then the nucleophile attacks the carbocation, resulting in the substitution product.
What is the rat-limiting step in a Sn1 reaction?
The leaving group leaves, generating positively charged carbocation
The more _____, the carbocation, the more _______. Why?
The more substituted
The more stable
Because the alkyle groups act as electron donors, stabilizing the positive charge
Why does the rate of the reaction depend only on the concentration of the substrate?
Because the formation of the carbocation is the rate-limiting step, the rate of the reaction depends only on the concentration of the substrate: Rate= k [R-L], where R-L is an alkyl group containing a leaving group.
What is Sn1 an example of?
This is a first-order reaction. Anything that accelerates the formation of the carbocation will increase the rate of an Sn1 reaction
Why is the product usually a racemic mixture?
Because Sn1 reactions pass through a planar intermediate before the nucleophile attacks.
In a Sn1 reaction , the incoming nucleophile can attack the carbocation from either side, resulting in what?
Varied stereochemistry
What is the long name for Sn2 reactions?
Biomolecular nucleophilic substitution reactions
How many steps do Sn2 reactions have?
1 step
What happens in Sn2 reactions?
Nucleophile attacks the compound at the same time as the leavig group leaves.
Why are Sn2 reactions called concerted reactions?
Because this reaction has only one step
Why are Sn2 reaction called biomolecular?
Because this single rate-limiting step involves two molecules
What is a backside attack in a Sn2 reaction?
The nucleophile actively displaces the leaving group
What must happen for a backside attack to occur in a Sn2 reaction?
The nucleophile must be strong, and the substrate cannot be sterically hindered
The less _____ the carbon in a Sn2 reaction, the more _____ . This is opposite of _______.
The less substituted
The more Reactive
Opposite of Sn1
What are the two reacting species in the single step of Sn2?
The substrate (often alkyl halide, tosylate, or mesylate) and the nucleophile
What has a role in determining the rate ina Sn2 reaction? What is the equation?
The concentration of both have roles
Rate= k[Nu:][R-L]
Sn2 reactions are accompanied by what?
Inversion of relative configuration
The position of substituents around the substrate carbon will be inverted
If the nucleophile and leaving group have the same priority in their respective molecules, then what happens in a Sn2 reaction?
The inversion will also correspond to a change in absolute configuration from (R) to (S) or vice versa
What are oxidation-Reduction reactions?
The oxidation states of the reactants change.
What is oxidation state?
An indicator of the hypothetical charge that an atom would have if all bonds were completely ionic
How can oxidation state be calculated?
From the molecular formula for a molecule
Carbon in methane has a oxidation state of what? Why?
CH4 has an oxidation state of -4 because the hydrogens eac hhave an oxidation state of +1. This is the most reducced for of carbon.
In carbon dioxide, each oxygen atom has a oxidation state of what? What about the carbon?
oxygen: -2
Carbon: +4
For an ion, the oxidation state is simply what? Expalin.
The charge, so Na+ and S 2- would have oxidations states of +1 and 2-
Carboxylic acids are more oxidized then what? Which are more oxidized then what?
More than Aldehydes, ketones, and imines
Which are more oxidized then alcohols, Alkyl halides and amines
What is oxidation?
An increase in oxidation state, which means a loss of electrons. In organic chemistry, it is often easier to view oxidation as increasing the number of bonds to oxygen or other heteroatoms (atoms other than carbon and hydrogen)
What is reduction?
A decrease in oxidation state, or a gain in electrons. In organic chemistry, it is easier to view reduction as increasing the number of bonds to hydrogen
When does oxidation of a carbon occur?
When a bond between a carbon atom and an atom that is less electronegative than carbon is replaced by a bond to an atom that is more electronegative than carbon. In practice, this usually means decreasing the number of bonds to hydrogen and increasing the number of bonds to other carbons, nitrogen, oxygen or halides.
What is the oxidizing agent?
The element or compound in an oxidation-reduction reaction that accepts an electron from another species.
Why is the oxidizing agent reduced?
Because the oxidizing agent is gaining electrons
Good oxidizing agents have what?
A high affinity for electrons or unusually high oxidation states.
What are examples of good oxidizing agents with a high affinity for electrons?
O2
O3
Cl2
What are good oxidizing agent examples with unusually high oxidation states?
Mn 7+ in permanganate (MnO4-)
Cr 6+ in chromate (CrO4 2-)
How can alcohols become aldehydes? What about carboxylic acids?
They become oxidized by one level or can be further oxidized to form carboxylic acids.
What oxidizing agents cause the reaction of alcohol to go all the way to carboxylic acid?
Using strong oxidizing agents
Chromium trioxide (CrO3)
Sodium or potassium dichromate (Na2Cr2O7 or K2Cr2O7)
What oxidizing agents cause the reaction of alcohol to stop at aldehydes?
Pyridinium Chlorochromate (PCC)
Secondary alcohols can be oxidized to what?
To ketones
What are the two themes to notice on oxidation reactions?
They feature an inccrease in the number of bonds to oxygen
Oxidizing agents often contain metals bonded to a large number of oxygen atoms.
When does reduction of a carbon occur?
When a bond between a carbon atom and an atom that is more electronegative than carbon is replaced by a bond to an atom that is less electronegative than carbon. This usually means increasing the number of bonds to hydrogen and decreasing the number of bonds to other carbons, nitrogen, oxygen, or halides
What are examples of good reducing agents?
Sodium Magnesium Aluminum Zinc Metal hydrides like CaH2 LiAlH4 NaBh4
What makes a good reducing agent?
Have low electronegativities and ionization energies
What reaction is _____ which involves aldehydes and ketones to be reduced to what?
Exergonic
Aldehydes and ketones
The aldehydes and ketones reduction reaction is exceedingly ______.
Slow without a catalyst
Amides can be reduced to ______ using ______.
Amines using LiAlH4
What reducing agent will reduce carboxylic acids to ________ and esters to ________.
LiAlH4 will reduced carboxylic acids to primary alcohols
Esters to to a pair of alcohols
What are the two themes to notice on reduction reactions?
Tend to feature an increase in the number of bonds to hydrogen, and reducing agents often contain metals bonded to a large number of hydrides
What is chemoselectivity?
The preferential reaction of one functional group in the presence of other functional groups
What determines the reactive site of a molecule?
On the type of chemistry that’s occuring
A redox reagent will tend to act on what reactive location?
The highest priority functional group
In a molecule with an alcohol and carboxylic acid group, a reducing agent is more likely to react on what?
The carboxylic acid than the alcohol
Reactions involving nucleophiles and electrophiles, where is the reaction site usually? Why?
At the highest priority functional group because it contains the most oxidized carbon. A nucleophile is looking for a good electrophile; the more oxidized the carbon, the more electroneagtive groups around it, and the larger partial positive charge it will experience.
In a nucleophile and electrophile reaction , if a molecule has carboxylic acid and alcohol, ketone and aldehyde, which will be the reactive site?
Carboxylic acid and their derivatives are first
followed by aldehyde or ketone
followed by alcohol or amine
Aldehydes are generally more reactive toward nucleophiles than ketones because they have less steric hinderance
What is a common reaction site on the MCAT?
The carbon of a carbonyl, which can be found in carboxylic acids and their derivatives, aldehydes, and ketones
Why is the carbon in carboxyl a common reaction site?
Within a carbonyl-containing compound, the carbon of the carbonyl acquires a positive polarity due to the electronegativity of the oxygen. Thus, the carbonyl carbon becomes electrophilic and can be a target for nucleophiles. Further, the alpha-hydrogen are much more acidic than in a regular C-H bond due to the resonance stabilization of the enol form. These can be deprotonated easily with a strong base, forming an enolate. The enolate then becomes a strong nucleophile, and alkylation can result if good electrophiles are available
What is a good reaction site in substitution reactions?
The substrate carbon in substitution reactions
In Sn1 reactions, what type of a carbon do they prefer as reaction sites? Why?
Tertiary to secondary carbons as reactive sides and secondary to primary.
Because they have to overcomes the barrier of carbocation stability
In Sn2 reactions, what type of carbons do they prefer? Why?
Methyl and primary carbons are preferred over secondary and tertiary carbons because they have a bigger barrier in steric hinderance
What is steric hindrance?
The prevention of reactions at a particular location within a molecule due to the size of substituent groups.
Sn2 reactions wont occur with what?
With tertiary substrates
What can be a useful tool in the synthesis of desired molecules and the prevention of the formation of alternative products?
Steric protection can be a useful tool in the synthesis of desired molecules and the prevention of the formation of alternative products.
What makes it impossible for the nucleophile to reach the most reactive electrophile sometimes?
Bulky groups make it impossible for the nucleophile to reach the most reactive electrophile, making the nucleophile more likely to attack another region.
What’s another way sterics come into play?
In the protection of leaving groups. Once can temporarily mask a reactive leaving group with a sterically bulky group during synthesis.
What are examples of a steric protecting a leaving group?
Reduction of a molecule containing both carboxylic acids and aldehydes or ketones can result in reduction of all of the functional groups. To prevent this, the aldehyde or ketone is first converted to a noreactive acetal or ketal, which serves as the protecting group, and the reaction can proceed. Another protective reaction is the reversible reduction of alcohols to tert-butyl ethers.
what are the 6 steps to problem solving?
- Know your nomenclature
- Identify the functional groups
- Identify the other reagents
- Identify the most reactive functional groups
- Identify the first step of the reaction
- consider stereoselectivity
Step one in problem solving involves knowing what?
Compounds IUPAC and common names
What questions should you ask when identify functional groups?
What functional groups are in the molecules? Do these functional groups act as acids or bases? How oxidized is the carbon? Are there functional groups that act as good nucleophiles, electrophiles, or leaving groups?
What questions should you ask when identifying other reagents?
Are they acidic or basic? Are they suggestive of a particulare reaction? Are they good nucleophiles or a specific solvent? are they good oxidizing or reducing agents?
How do you identify the most reactive functional groups?
More oxidized carbons tend to be more reactive to both nucleophile-electrophile reactions and oxidation-reduction reactions. Note the presence of protecting groups that exist to prevent a particular functional group from reacting.
If the reaction involves an acid or base what will be the 1st step?
Protonation or deprotonation
If the reaction involves a nucleophile, what will be the 1st step?
For the nucleophile to attack the electrophile, forming a bond with it.
If the reaction involves an oxidizing or reducing agent, what will be the 1st step?
The most oxidized functional group will be oxidized or reduced
What questions should you ask, once you know what will react when identifying the 1st step?
Did the protonation or deprotonation of a functional group increase its reactivity? When the nucleophile attacks, how does the carbon respond to avoid having five bonds? Does a leaving group, or does a double bond get reduced to a single bond (like the opening of a carbonyl)?
If there is more than one product, the major product will be determined how?
By the difference in strain or stability between the two molecules.
What makes a molecule more strained?
Molecules with significant angle, torsional or nonbonded strain.
Are more strained or less strained molecules more likely to form?
More strained molecules are less likely to form than less strained molecules
Products with conjugation are less more more stable then those without?
More stable
