Exam 3 Flashcards
two factors that tell us of a reaction is favorable
thermodynamics: is there enough energy?
kinetics: how fast?
enthalpy
- ΔH or q
- heat energy exchange between a reaction and it surroundings at a constant pressure
- also the amount of energy required to form or break bonds
endothermic
- ΔH>0
- energy is required from surroundings
- temperature decreases during reaction
exothermic
- ΔH<0
- reaction gave up energy the the surroundings
- temperature increases during reaction
entropy
- ΔS
- amount of disorder or randomness
ΔS<0
multiple molecules come together to form a smaller number of molecules
ΔS>0
smaller number of molecules break apart to form a larger number of molecules
gibbs free energy
- 🔼G
- measures spotaneity of a reaction by taking entropy and enthalpy into account
what does a negative 🔼G say about the reactants and products?
the reaction favors the products
factor affect reaction rate
- concentration of reactants
- Activation energy
- temperature
- geometry and sterics
- presence of a catalyst
What levels of activation energy are favorable?
small AE
what does A stand for in k=Ae^(-Ea/RT)
a factor taking geometry into consideration
what allows temperature to influence the rate of the reaction?
temperature affects the rate constant
transition state
- an energy maxima on a reaction pathway
- barely exist for a moment, cant be observed
- bonds are in the process of being broken and formed
- unstable af
exergonic reaction
- products are favored at equilibrium
- spontaneous
- products have lower amount of free energy than reactants
- 🔼G
- Keq>1
endergonic reaction
-reactants favored at equilibrium
-nonspontaneous
-products have more free
energy than reactants
-+🔼G
-Keq<1
intermediate
- state occurring at an energy minimum
- usually exist long enough to be observed
- bonds are not in the process of forming and breaking
- species are fully formed and can be isolated
which points on energy diagrams are structurally similar?
points that are close to each other
Hammond postulate
- In an exergonic process, the transition state is closer in energy to the reactants and therefore is more structurally similar to the reactants
- in an endergonic process, the transition state is closer in energy to the products and therefore more structurally similar to the products
nucleophile
- loves attacking nuclei
- atoms that carry partial negative charges, an available pair of electrons or a pi bond
- large atoms
- ARE electron dense
electrophile
- electron loving
- electron deficient
- can accept a pair of electrons, or has a + partial charge
- carbocations
what makes nucleophiles have have nucleophilic characteristics?
polarizability: ability of an atom to distribute its electron density unevenly in response to external influences
Which atoms can have a + charge and not be electrophiles?
O+ or other atoms with 4 bonds that would exceed the octet rule if the
nucleophilic attack
- has forms with 1 and 2 arrows
- nucleophile attacks an electrophile
- tails of arrows start on electron(- charge)
- head of the arrow ends on a nucleus(+ charge)
- electrons are shared, not transferred
loss of a leaving group
- a bond breaks and one atom from the bond takes both electrons
- almost always a halogen attached to a carbon
proton transfer
- acid/base reactions
- a base gets protonated: uses pair of electrons to take an H+ from the acid
- group gets deprotonated
- multiple arrows may be necessary
- first arrow starts from electrons of base to H
- first arrow ends at H
- second arrow starts at bond with H and ends at the other atom
hyperconjugation
- stabilization of carbocations by neighboring groups through slight orbital overlap in the same plane
- responsible for the stabilization of the staggered conformation alkenes over the eclipsed formation
What might happen before a molecule can react with a nucleophile?
intramolecularly arrange to become more stable
carbocation rearrangements
- types types: hydride shift and methyl shift
- only occur from an adjacent C
- 1 arrow moving 2 electrons
- MUST increase stability by looking at substititution
alkyl halides
- usually the substrate of substitution and elimination reactions
- C(alkyl) bonded to a halide
- always the substituents when naming using IUPAC
substrate role in reactions
- starting material
- predominately attacked in reactions
Iodine nomenclature
iodo
Br nomenclature
bromo
Cl nomenclature
chloro
F nomenclature
fluoro
where do substitutions occur?
alpha carbon
in what circumstances do substitution and elimination reactions compete with each other?
When a reagent can function as a nucleophile or a base
what is the most common type of carbon for a substitution or elimination reaction to occur at?
sp3 hybridized carbon atom
Functions of halogen in alkyl halide
- Withdraw electron density via induction making the carbon it is attached to electrophilic
- serve as a leaving group where substitution and elimination reactions can only occur when a leaving group is absent
how is electronegativity related to stability?
directly
what determine leaving group quality?
stability of the base
products of elimination reactions
alkenes
how do you know which carbon is the locant when naming alkenes?
the first carbon with the lowest number on the double bond is the locant
which alkenes are stable in rings with less than 8 atoms?
cis alkenes
what is special about an 8 membered alkene ring?
it is the smallest ring that can have a trans double bond and be stable at room temperature
What type of bonds are the pi bonds typically in an alkene ring and why?
usually cis/Z due to ring strain. true in all rings with less than 8 atoms
stability of cis vs trans isomers and why
trans isomers are more stable due to lack of steric strain, in trans formation the biggest groups are opposite of each other
Nucleophilic substitutions
- always involve nucleophilic attack and loss of a leaving group
- order can vary
- inclusion of proton transfer or rearrangement can vary
concerted substitution
nucleophile attacks and the leaving group leaves simultaneously
stepwise substitution
leaving group leaves then nucleophile attacks
Why can a nucleophilic attack occur first during a substitution reaction?
it would violate the octet rule
What does each part of Sn2 stand for?
S=substitution
N=nucleophilic
2=bimolecular
What effects a concerted Sn2 mechanism?
- kinetics
- substrate structure
- nucleophile strength
- solvent effects - stereochemistry
Kinetics of a concerted Sn2 reaction
- one step
- one transition state
Effects of substrate structure on kinetics of a concerted Sn2 reaction
Less sterically hindered electrophiles react more readily under Sn2 conditions because steric interactions cause the activation energy to increase which slows the reaction. More substituted slows the reaction
Effect of nucleophile on kinetics of an Sn2 concerted mechanism
- rate of reactions depends on concentration and strength of nucleophile
- strong nucleophiles speed up the reaction
- weak nucleophiles slow the reaction and give other reactions a chance to occur
- rate=k[substrate][nuc]
Factors affecting nucleophile strength
- Negative charge makes atoms more reactive when the nucleophilic atom is the same
- Atoms: less electronegative=stronger in the same row and larger=stronger in the same column due to polarizability
- smaller molecules are better nucleophiles, large molecules have a harder time fitting into smaller spaces
opposite of ARIO
characteristic of weak nucleophiles
neutral charge
polar aprotic solvents vs polar protic
polar protic solvents can H bond, aprotic solvents do not
effect of solvents on bimolecular processes
polar aprotic solvents promote bimolecular processes by stabilizing and surrounding the counterion that would attach to the nucleophile otherwise, leaving the nucleophile mostly naked and ready to attack the electrophile. This raises of the energy of the nucleophile/base and lowers the activation barrier
what happens in bimolecular processes when the solvent is polar protic
the counterion gets solvated
how do solvents impact nucleophilicity?
These effects are most important in halides
in polar protic sovlents: bottom of the periodic table has the highest nucleophilicity
polar aprotic solvents: top of the periodic table has highest nucleophilicity
effects of solvation on reactions
solvation stabilizes things
effects and characteristics of stereochemistry in Sn2 reactions
- has inversion of configuration where reactant and products are opposite configurations with chiral alpha carbons
- stereospecific: configuration of product depends on starting material
- diagnostic
- observed in lab using specific rotation to differentiate enantiomers
what is required for inversion of configuration
nucleophile can only attack from the back side
Why do nucleophiles attack from the backside in Sn2 reactions
- Back side is opposite of leaving group and therefore less hindered with electron density because lone pairs of leaving group create regions of high electron density that block the front of the substrate. This allows LUMO and HOMO to match up .
- nucleophile must approach the backside to allow proper orbital overlap that is necessary for bonding
Location of node in Sn2 rections
between C and leaving group bond
what effects do concerted reactions have on the chiral center?
this causes the chiral center to behave like and umbrella blown inside out in the wind. The molecule is flat in its transition state
What happens when an alkyl halide is treated with a strong base?
- it can undergo beta elimination(1,2-elimination) to form an alkene
- E2 elimination reaction competes with Sn2
- The competition originates from Strong nucleophiles and strong bases interacting
- 1 arrow goes from the e- pair of the base to the H in the H-C bond, then from the H-C bond to the alpha-beta C-C bond to make an alkene bond(proton transfer). 3rd arrow from from alpha C-X bond to X(loss of a leaving group)
- always has 3 arrows
- 3 arrows occur simultaneously
what does the rate of an E2 reaction depend on?
concentration of the attacking molecule and the strength of the base
how does base strength affect E2 reactions
strong base speed it up and weak bases slow it down
How do you know if a base is strong?
use ARIO
function of the reagent in substitution reactions
reagent functions as a nucleophile that attacks the electrophile
function of reagent in elimination reactions
functions as a base that abstracts protons
weak bases and weak nucleophiles
H2O and ROH
strong nucleophiles and weak bases
Halides, HS-, RS-, NC-, RCOO-, PR3
strong bases
HO-, RO-, H2N-, R2N-, RC-
what type of substrates favor E2 reactions and why?
tertiary, it should proceed through a more stable and kinetically favorable transition state and produce a more stable and thermodynamically favorable product. In the transition state a double bond forms and it should be more substituted for stability
Which forms of alkenes are more stable?
trans and E formations
regioselectivity
- multiple reactive sites on a molecule resulting in multiple possible products(Zaitsev and Hoffman).
- Only occurs when one product is favored over the other
- E2 reactions
What affects regioselectivity in E2 reactions?
ratio of Zaitsev and Hoffman product depends on the bulkiness of the base
regioselective vs regiospecific
regioselective makes at least 2 different kinds of products while regiospecific does not
What do sterically hindered bases favor in E2 reactions and why?
sterically hindered bases favor Hoffman products because Hoffman bases are less substituted and the bulky base has an easier time reaching the H to abstract
How does substrate hinderence affect the likeliness of a nulceophilic attack
more hindered substrate makes nucleophilic attacks less likely
stereoselective in E2 reactions
produces multiple products in unequal amounts
stereospecificity
- only one stereoisomer is produced
- E2 reactions are stereospecific when only one beta hydrogen can be eliminated
When is the Z formation more favored?
when the a product is stereospecific to the Z outcome in E2 reactions
What is required to break bonds in pi bonds?
atoms must be rotated into the same plane to that the P orbitals can overlap(co-planar)
co-planar
atom in which bonds are broken involving the formation of a pi bond and these atoms are in the same plane
syn-coplanar
- atoms on the same side of the pi bond
- unstable
- eclipsed formation
- torsional strain
- less common than anti-coplanar
antiperiplanar
- anti-coplanar for molecules with an approximate 180 degree dihedral angle
- staggered
- proceed by a much lower energy transition state than syn-coplanar
what do E2 mechanisms depend on in terms of the configuration of planar molecules around a pi bond?
they depend on the configuration of the alkyl halide
when is stereospecificiuty relevant?
when the beta position has just one proton
what has to be done when a beta position has 2 protons in E2 reactions?
either proton can be rearranged so that is is antiperiplanar to the leaving group
what stereochemistry do antiperiplanar E2 reactions have?
stereoselective
regiospecific
one possible alkene is made
what is required for a molecule to be regio and stereoselective
2 hydrogens on left and right beta carbons
hehydrohalogenation
elimination of a hydrogen and a halogen
requirements for E2 reactions to occur with cyclohexanes
- leaving group must be axial to an antiperiplanar H
- H’s on must be on beta carbons and be trans in cyclohexanes
rate equation for unimolecular reactions
rate=k[substrate]
starting step of unimolecular reactions
ionization of the substrate and loss of a leaving group
second name for E1/Sn1 and origin of the name
solvolysis because the nucleophile is also the solvent
qSn1 mechanism
- loss of a leaving group followed by a nucleophilic attack, often followed by a proton transfer
- stepwise mechanism
rate determining step
slowest step in a multi-step mechanism
rate determining step in Sn1 reactions
carbocation intermediate because it is the highest energy transition state, so forming it takes the most effort. it has the highest activation energy
what type of reaction is Sn1 in terms of free energy?
exergonic
difference between E1 and E2 reactions
- same core steps, but they don’t occur a t the same time in E1
- In E1, the solvent functions as a base instead of a nucleophile
function of the base in E1 reactions
deprotonate the carbocation to form an alkene
kinetics of E1 reactions
- same as Sn1
- rate determining step is the formation of the carbocation
how does heat is affect reactions?
favors E1
what type of solvent favors unimolecular interactions and its role
polar protic solvent-bonds with nucleophile to stabilize it while the leaving group leaves first. It also stabilizes the full and partial charges that form during the mechanism to lower activation barriers.
what happens to cations and anions in unimolecular reactions?
they are solvated
which substrates allow unimolecular reactions to happen fastest and why
tertiary substrates because a carbocation intermediate must be formed. secondary substrates can react but very slowly
Why does the tertiary carbocation have a lower Ea than the secondary carbocation?
If a carbocation is more substituted, it should be more stable because of hyperconjugation
factors affecting stability of carbocations
- induction
- resonance
- hyperconjugation
When can primary substituted carbons form carbocations?
under resonance stabilized conditions
why cant vinyl or aryl halides undergo substitution?
they form a very unstable carbocation
how do leaving groups affect the rate of reactions?
the ability of a leaving group to leave the molecule can affect the rate of a reaction
good leaving groups(halides) and why
bottom of the periodic table is more reactive and leaves the group more easily, bottom to top. Good leavings groups are also weak bases and I- is the weakest base
is OH a good or bad leaving group and why?
bad because it would make OOH, it must be converted into a better leaving group
rate of carbocation rearrangement in unimolecular reactions
occurs very quickly
what do unimolecular reactions with rearrangements usually result in?
a large mixture of products
Do rearranged or un-rearranged products get favored and why?
rearranged products in general because carbocation rearrangement is faster so it is intramolecular and the non-rearranged reactions are intermolecular
stereochemistry of Sn1 reactions
- carbocation is planar and either side can be attacked by the nucleophile with equal likelihood
- both retention and configuration are observed
- trigonal planar molecules
- stereoselective
- key intermediate is flat
- makes racemic mixture with preference for inverted form
trigonal planar stereochemistry
flat
difference in stereochemistry of Sn1 and Sn2 reactions
Sn2 has 100% inverted products whereas Sn1 has a mixture
what type of stereochemical product gets produced more in Sn1 reactions?
inversion
Why is retention less produced in Sn1 reactions?
leaving group will form an ion pair with the carbocation, making it more difficult for the nucleophile to attack from the same side
regiochemistry of E1 reactions
- regioselectivity is determined by final step
- generally produce more Zaitsev products because
stereochemistry of E1 reactions
- in the last step, a proton is removed from a beta carbon adjacent to the sp2 hybridized carbocation
- trans is favored over cis because the trans product is less sterically hindered, lower in energy and more stable
🔼S of elimination vs substitution reactions and why
eliminations has a larger 🔼S than substitution reactions because elimination results in more products which indicates more disorder
Base vs nucleophile reagent effects if a rearrangement happens first
bases encourage elimination while nucleophiles encourage substitutions if a rearrangement happens first
how do substitution and elimination reaction affect and interact with each other?
they are almost always in competition with each other
how to determine the function of a reagent
determine is it is strong/weak and determine if it is a base/nucleophile
what does the reagent tell you about the reaction mechanism?
if it is substitution or elimination
products of only strong nucleophiles
very strong conjugate acids
CN stregth, basicity and nucleophilicity and why
strong nucleophile, weak base because the carbon is sp hybridized
acetate strength, basicity and nucleophilicity and why
strong nucleophile weak base because it has an O- with resonance
what do bulky bases as reagents promote?
elimination
strong nucleophile and strong bases category
- E2 or Sn2
- includes N containing reagents, O- or N- that arent big
what do strength of reagents promote?
Strong: bimolecular
Weak: unimolecular
what does neutrality tell you about the strength of a reagent?
neutral indicates weak strength
How is a specific product favored with a weak nucleophile or base?
tertiary substrates
regiochemical outcome of Sn2 reactions
nucleophile attacks the alpha position where the leaving group is connected
stereochemical outcomes for Sn2
nucleophile replaces the leaving group with inversion of configuration
regiochemcial outcome of Sn1
nucleophile attacks carbocation where the leaving is originally connected unless a rearrangements takes place
stereochemical outcome of Sn1 reacrtions
nucleophile replaces the leaving group with racemization
regiochemical outcome of E2 reactions
Zaitsev product is favored over Hoffman porducts unless a sterically hindered bas eis used, then Hoffman product is favored
Stereochemical outcome of E2
- stereoselective and stereospecific
- a transis favored over cis
- when the beta position of the substrate has only one proton alkene resulting frmo antiperplanar elimination will be obtained exclusively usually
regiochemical outcome of E1 reactions
Zaitsev product is almost always favored
stereochemical outcome of E1 reactions
- stereoselective
- trans>cis
strong nucleophile+strong base potential products
primary: E2 minor + Sn2 major
secondary: E2 major+Sn2 minor
tertiary: E2 only
why do E2 reactions have an antiperiplanar requirement and E1 reactions dont?
E2 reactions are concerted and E1 reactions are not
polar protic vs polar aprotic nucleophilicity
protic: bottom is more nucleophilic
aprotic: top is more nuclephilic
