135A organic - substitution, elimination and addition Flashcards
Alcohols are bad leaving groups. What can they be activated with (protonation of OH)
Acids/ HCl
how many substances are involved in the RDS
2 (varying the conc of both changes the rate)
how many substances are involved in the RDS
1(one one conc changes rate)
What areas on the molecule could nucleophilic sub (OH-) occur
What areas on the molecule could nucleophilic sub (OH-) occur
What areas on the molecule could nucleophilic sub (OH-) occur
What areas on the molecule could nucleophilic sub (OH-) occur
nowhere on the molecule
what does SN1 stand for
does SN1 have a carbonation intermediate
yes
primary/ secondary/ tertiary undergos SN1
tertiary (+ stable secondary cations with conjugation)
What is a carbocation structure
planar and sp2 hybridised carbon
What makes a carbocation stable? / conjugation and hyper conjugation
Could these molecules undergo SN1
1- (slow but) has conjugation due to double bond so could form a stable primary carbocation
2- very fast; conjugation and methyl groups
What factors effect wether something can undergo SN1 or SN2
Why do SN1 reactions give racemic mixtures
because the nucleophile has equal chance of attacking from the above or below/ planar carbocation
Which carbocation is the nucleophile more likely to attack/ which product will be the major
nucleophile will attack least sterically hindered/ primary will be major product
What does SN2 stand for
Does an SN2 have a carbocation intermediate
no- has transition state
What energy determines how fast a reaction will go
activation energy (higher Ea the slower the reaction)
In substitution how does the LUMO and HOMO of the reactants interact (nucleophile and electrophile)
HOMO of nucleophile and LUMO of electrophile. For a Y- the HOMO is the lone pair
The HOMO of the nucleophile goes to what bonding orbital of the electrophile
the σ* anti bonding orbital (when electrons fill it the bond breaks)
In SN2, what angle must the nucleophile and electrophile orbitals align in order to react (transition state where they leave and join simultaneously)
180°
primary/ secondary/ tertiary undergos SN2
primary and some secondary (minimal steric hinderance so nucleophile can get to σ* c-x bond)
Of primary carbocations what will increase the rate of SN2 substitutions
Reaction is faster if the carbocation is more stable/ conjugation
What is SN2 inversion
The leaving group and going group will not be of same orientation if the reaction takes place at the chiral centre
What is SN2 inversion
The leaving group and going group will not be of same orientation if the reaction takes place at the chiral centre
What would be the transition state for this reaction
Why are primary carbocations with less CH3 groups on it faster at SN2 than ones with
Less steric hinderance
What is torsional strain
Strain when hydrogens are on the same side of a cyclic ring
Why are ring compounds predicted ROR always different than recorded
Predictions assume rings always flat/ planar, but rings are actually arranged to have minimum energy conformation (chair)
How is torsional strain minimised
puckering
What are the bond angles/ structure shapes of the carbons
tetrahedral 109°
Which C-H bonds are axial and which ones are equatorial
What does a “ring flip” do
Equatorial and axial swap positions
Is the biggest group more favourable in the axial or equatorial position
equatorial
Are the hydrogens more favourable in the axial or equatorial position
equitorial because they are less sterically hindered
Why does the first reaction have a faster SN2
The leaving group is OTS. It is more favourable to leave/ easier accessible in the equatorial position
Why does t-Bu stay equatorial and its the other group that flips
t-bu can only be equatorial (conformational lock)
What effects the strength of a leaving group
C-X bond strength and stability of leaving group anion X-
What makes a good leaving group
- good leaving group is the conjugate base of a strong acid pKa is low
- weak C-X bond so X can easily leave
What makes a good leaving group
good leaving group is the conjugate base of a strong acid pKa is low
Which halide will be the best leaving group
Iodine- has weakest C-X bond
Is OH a good leaving group
no- H2O (con acid) has a pKa of 14, so it is a very weak acid
How does this alcohol get activated by the strong acid
H2O is a good leaving group, so Br can be installed on the alkyl instead
is water a good leaving group
Why does this react via Sn1
tertiary substrates cannot do Sn2
Draw a curly arrow mechanism for the following activation of an alcohol
no stereochemistry to worry about because its primary
What is the shorthand for a sultanate ester
TsOH
Are sultanate esters good leaving groups
yes
An alcohol being activated by being turned into a sultanate ester. What are the steps in this reaction
An alcohol being activated by being turned into a sultanate ester. What are the steps in this reaction
Why is this reaction favourable
- Strong S-O bond formed
- SO2 gas is entropically favourable
What is the structure of SOCl2
What is the mechanism of this reaction
What does this mean
determine the stereochemistry
Sn2 inversion where there is stereochemistry
What conditions are needed for an Sn2 inversion
reaction needs to happen at a stereocentre (e.g.)
What is an ether
oxygen with two carbons either side
Are ethers good leaving groups
no- but can be protonated with a strong acid to make a better leaving group (oxygen gets protonated)
Why would there be no reaction here
ester is a bad leaving group
What is the mechanism for an ether being protonated by a strong acid to make it a better leaving group
the carbon on the other side of the oxygen is sp2
What are epoxides
cyclic ether
Are epoxides good nucleophiles
yes- do not need activation/ they want to be nucleophiles to remove ring strain
Why do epoxides want to remove ring strain and undergo SN2 reactions
all bond angles are 60°, but all atoms are sp3 hybridised so want to be 109°
What do epoxides turn into when undergoing SN2 reactions
alcohols
ring opening of an epoxide
Why does a nucleophile effect the rate of an SN2 reaction but not Sn1
because nucleophile is involved in the RDS of an Sn2 reaction
What makes a good nucleophile
- bases of a weak conjugate acid
- lower down the periodic table (this can disrupt weak con acid argument)
Which would be the best nucleophile
OH because it has the weakest con acid
If Y is a good nucleophile, where does the equilibrium lie
to the right
If Y is a good nucleophile what does that say about its conjugate acid Me-Y
it is a weak acid
Why are elements further down the period table better nucleophiles
less charge density/ electrons more available to do reaction
Why would a sulphur based nucleophile be a better nucleophile than an oxygen based one
note- if the reaction was Sn1, the nucleophile would have no effect on rate so the reactions would go at the same speed
bottom anion is more stable; electron withdrawing =O, and you can draw resonance structures where electrons are shared so less to use for reaction
Which reaction would go quicker
I is further down the periodic table, and less electronegative/ less charge density/ more e- available for reaction
what is a polar protic solvent
solvent that can undergo hydrogen bonding(H-N,O,F)
what is a polar aprotic solvent
have a dipole but has no H available for hydrogen bonding
What does a higher dielectric constant mean (ε)
a solvent is more polar
Sn1/Sn2 reactions favour which solvents polar protic/ aprotic
Sn1 faster in polar protic
Sn2 faster in polar aprotic
Why are SN1 reactions faster in polar protic solvents
polar protic solvents stabilise cations and anions. Intermediate has dropped E more than the starting material because it is charged and starting material is neutral
Their transition states will have lower energy; therefore lower activation energy
For an SN2 reaction why is the energy higher/ more favourable in a polar aprotic solvent
smaller Ea than polar protic
Why is the transition state less polar than the staring material
in transition state the charge is distributed over 2 atoms instead of localised on one in the starting
what are the conditions for an elimination reaction
- base to attack beta hydrogen
- form a relatively stable carbocation
What is a beta hydrogen
carbon next to group of interest/ leaving group is alpha, must be a hydrogen on the carbon next to it
What factors effect elimination reaction rates
What type of leaving group is needed for an elimination reaction
good leaving group/ con base of a strong acid
Are quaternary ammonium ions good leaving groups in eliminations
yes- not so good for substitutions because it is quite spherically demanding
Why do elimination reactions result in an increase in entropy
Elimination reactions with 2 reactants, give 3 molecules of products
Why are elimination reactions more favourable at higher temperatures
△S (entropy) is always positivie △G will always be more negative
What is the difference between a E1 and E2 reaction
E1= 1 species in RDS
E2= 2 species in RDS
What are the secondary carbocations that are stable enough to do an E1 elimination reaction
benzylic and allylic substances. Have additional π systems for conjugation
What type of bases can be used for E1 elimination reactions
weak bases; bases do not effect ROR of E1. Base must not act as a nucleophile to avoid competing substitution
How does H2SO4 react as a base in this reaction
H2SO4 protonates the OH leaving, HSO4- which is a poor base, but it doesn’t have to be a good base as its E1 and still can accept a proton
What is the difference between a base and a nucleophile, and why for elimination reactions do you only want a base
base= specifically attacks protons
nucleophile= donates e- to all other atoms
You only want a base for an elimination, so it will attack the β hydrogen to form an alkene. If you have a base that is also a nucleophile, the reaction will have competing substitution
What is the mechanism for this reaction
In an E1 reaction, for an alkene to form (π bond to be created) what needs to be true about the orbitals of the reactant where the cation charge is, and where the C-H (β bond) that is breaking is
empty p-orbital of cation and breaking C-H bond orbitals must be parallel. Assumption that the e- from the breaking C-H bond must move into the p orbital of the + charge from the diagram
The starting material doesn’t have specified stereochemistry. This is one possibility for what this molecule looks like with given sterics. What is the second way it could be arranged via bond rotation
This is for an elimination reaction where the beta hydrogen leaves. Which steric has the lowest energy conformation and will therefore lead to the major product
second as it is **least sterically hindered
** First one- Ph and Me are too close to each other
In E1 elimination reactions, will E or Z isomers for the product be favoured
E isomers have lower energy conformations in the intermediate carbocations
more/less substituted alkenes are more stable
more substituted alkenes are more stable/ transition state leading to more substituted alkene is lower in energy
Why are more substituted alkenes more stable
stabilised through hyperconjugation of their empty π* anti-bonding orbital with adjacent C-H or C-C orbitals
In an E1 elimination, which product had the most stable transition state
the one most on the right/ more substituted products will have had more stable transition states because of hyperconjugation stabalisation (adjacent alkyl groups give adjacent C-C and C-H bonds)
What is an E2 elimination
elimination with 2 species in RDS. bonds break and form simultaneously
What is an E2 elimination
elimination with 2 species in RDS. bonds break and form simultaneously
What does the word antii-periplanar mean in terms of an E2 reaction
hydrogen atom and the leaving group must be anti-periplanar to each other for maximum orbital overlap (180° to each other). This is given by a staggered conformation
Why can primary alkyl substances only undergo E2 reactions
because they form a very unstable carbocation (nothing to conjugate or hyper conjugate with)
What is needed for an E2 reaction
- good leaving group
- beta hydrogen
- strong base usually sterically demanding
- can be primary tertiary or secondary
tertiary alkyl substances can undergo SN2/E2 but cannot undergo SN2/ E2
Cannot undergo SN2, but can do E2
Why can only certain substituted cyclohexanes undergo E2 elimination
leaving group must be axial for E2 elimination. Beta hydrogens must be anti-periplanar to leaving group
Elimination is nucleophilic attack on carbon/hydrogen while substitution is attacking carbon/hydrogen
elimination attacks hydrogen
substitution attacks carbon
more basic nucleophiles favours E2/SN2. Basic=weak con. acid/ more affinity for attacking a proton
elimination
What reaction will a Br- nucleophile typically undergo
SN2
Will a higher concentration of a base impact the rate of an E2 elimination reaction (base attacks the H and removes it to form a C=C)
higher conc of base- accelerated reaction
Charged bases/nucleophiles will tend to perform E1/SN1/SN2/E2 reactions.
Wheras neutral bases/nucleophiles will be E1/SN1/E2/SN2
Charged bases/nucleophiles will tend to perform SN2/E2 reactions.
Reactions where neutral bases/nucleophiles are involved tend to go through carbocations (i.e. they tend to be SN1/E1).
What does the measure of basicity tell you about a nucleophile
the ability of a species to accept a proton
What makes a strong base
weak conjugate acid (high pKa)
Bases are used in elimination and substitution reactions. More sterically demanding bases favour elimination/substitution
sterically demanding bases favour elimination, easier for them to not get as close and remove the H to form C=C than to substitute/attach onto a substance. It is difficult for a large base to get in by the carbon to do SN2
Why does this reaction only do E2 not SN2
KOt-Bu is a large base/nucleophile and so favours more accessible β hydrogen than trying to attach itself
Why does this reaction favour substitution not elimination. However there is a small amount of elimination at would it be E1/E2
- most sub- base/nucleophile is quite small so can substitute instead of just take β hydrogen
- Would be E2 as its primary (E1 is tertiary and some secondary)
How do each of these effect wether a reaction is E1/E2
E1- can have any base/ usually weak because strong bases go E2. Electrophile must be very stable carbocation (tertiary and some secondary). leaving group must be good.
E2- strong bases. Primary, secondary or tertiary. β hydrogen atom. Good leaving group.
What do both of these look like as a newman projection and which ones the least sterically hindered so more likely to go on and form a major product in an E2 reaction
2 is more sterically hindered so will make a minor product. Elimination can happen at both because both have a Br and H anti-periplanar, but there will be more product from projection 1
What would this newman projection look like drawn out with stereospecifics (forget its going to a transition state)
Explain why each transition state produces and E or a Z isomer (either Me are on same side or on opposite)
First one gives Me on opposite sides because one Me is hashed and one is blocked
Second one gives Me on same side because both Me’s are hashed
Which transition state has the higher energy
bottom one- most sterically hindered because the Me’s are on the same side
This is an E2 reaction. Why does the bromine leave but not the flourine
bromine is a better leaving group (further down table)
Why are bulky groups better leaving groups (ie. things further down the periodic table)
Bulky groups are better leaving groups as when they leave, the steric factor gets stabilised
Draw this molecule as a newman projection
Draw this out as a molecule
Why could this newman projection transition state not be used in an E2 reaction and must be rotated
H and Br need to be on opposite sides/ anti-periplanar/ at 180°; projection must be rotated to get the correct transition state that will give the major product
What is a stereoselective reaction vs a stereospecific reaction
stereoselective- no specific stereochemistry given so can get multiple different product stereochemistry
stereospecific- starting material determines stereochemistry of product
Fill in with either less/more
hindered bases attack most accessible hydrogen atoms
A hindered base attacks a hydrogen with lots of substituted groups around it and one without as many. Which transition state will be higher
hindered bases attack most accessible hydrogen atoms; transition state on way to more substituted product will be higher in energy due to more steric demand
What is an E1cB reaction
- deprotonation to make an anion
- By its own accord the anion moves electrons to kick out the leaving group to leave an alkene
This is an E1cB reaction. After the anion is formed, how would this form an alkene
substrates that undergo E1cB reactions must be able to form what
How do you decide which bromine leaves
must be the right hand Br because it is on an sp3 hybrided carbon; cannot have substation on sp2 hybridised (if cation did form there, there would be not additional stabilisation)
How to decide whether its SN1 or SN2
acetone is polar aprotic so must be SN2
What can alkenes act as nucleophile/electrophile
nucleophile π-bond (HOMO) of alkene with LUMO of electrophile forms addition products
What is the mechanism for this simple alkene addition
bromine acts as a nucleophile once the carbocation is made
Why does this only have the one product and not the other carbocation
the most stable carbocation route is take
What is the Markovnikov’s Rule (alkene HX addition rule)
on addition of HX to an alkene, the hydrogen adds to the least substituted carbon atom
Draw “curly arrow” mechanisms to determine the major products from the following reactions
What needs to be present for an anti-Markovnikov’s product to be formed (hydrogen doesn’t go on the least substituted carbon)
peroxide -the least-substituted alkyl halide is formed as the major product
How can a radical be formed
homolyses high heat or light
What are alkyl radicals stabilised by
hyper-conjugation and conjugation
What are the three steps of a radical reaction
Initiation- making the radical
Propagation- radical reacting with non-radical
termination- radical and radical
Why is it the O-O bond that breaks
O-O bonds are very weak
How would this radical react with HBr in a propagation step
Is a primary or tertiary methyl radical more stable; which radical is more likely to be formed in a propagation step
tertiary- therefore in a propagation step, if the methyl radical is being made again the tertiary one will be made/ primary would have higher energy transition state
How would this propagation step react and form
forms tertiary radical rather than primary as it is more stable/ transition state lower in energy
propagation step product
What would each of these termination steps look like
What does an alcohol and H2SO4 make
alkene (elimination reaction)
halogenoalkane and CN
nitrile
What is a meso compound
non-optically active member of a set of stereoisomers, at least two of which are optically active
What is a meso compound
non-optically active member of a set of stereoisomers, at least two of which are optically active
What would the the transition state for this
Why does this reaction make a racemic mixture
bromine could attack from either face
Draw the ORBITALS on of Br- adding onto the cation (Br attacks 180° to Br+)
What is the curly arrow mechanism for this (Br2 ring)
Does Br2 have fumes
yes
What does NBS look like
Why is NBS used in a reaction where you need bromine instead of bromine
bromine fumes, and NBS provides a constant, low concentration of Br2 through reaction with trace HBr
fill in gaps with more/less
more substituted/ Z isomers/ 1,1
Which alkenes will have a faster rate of reaction
more substituted/ Z isomers/ 1,1 are more reactive
What are bromohydrins
Br and OH
ring opening Br+, but instead of Br- attacking, water attacks
A bromohydrin alcohol can be treated with a base to get an epoxide. What Is the mechanism for this (deprotonation)
this reaction is fast
brohydrin + base =
epoxide
Alkene+ Br2 +H2O =
bromohydrin
alkene + H —> alkane but under what conditions because it has a high activation energy
catalyst
With an alkene —-> alkane reaction, what is special about where the hydrogens add across the double bond
on the same face
alkene + H2O (in acidic conditions so H20 makes H30+) =
alcohols (OH adds to one end, last H adds to other) (H adds to least substituted end
How would this alkene get H off the surface of a catalyst
-absorbed onto metal surface
-H transferred onto one face of the alkene
▪ Products are single diastereoisomers (but either racemic or meso)
What is the mechanism for this
must form a stabilised tertiary carbocation intermediate
What reactant could be used for an oxidation reaction
hydrogen peroxide H2O2
Alkenes can undergo hyboronation (reacting with BH3) and then oxidation. What does this form
anti-maokovnikov alcohols ( substituent is bonded to a less substituted carbon, rather than the more substitued carbon)
BH3 is electrophilic/ nucleophilic
electrophilic/ can act as Lewis acid (electron acceptor) because of empty p orbital
hyboronation of alkenes can be due to reacting with BH3, or other derivatives such as
hyboronation has a ** four-membered transition state**; what would the this transition state
if H2 adds to the same face of an alkene, how could the products produced be meso
How do you form an epoxides from alkenes
peroxycarboxylic acid (peracid)
Are epoxides good nucleophiles
yes
What is the mechanism for an alkene + mCPBA to form an epoxide
HOMO of alkene (πC-C) interacts with LUMO of mCPBA (σ*O-O). The product will be racemic because the syn addition could add to either face
Which compound is meso
meso due to line of symmetry
Alkene + mCPBA = epoxide (include transition state)
ring could have attacked from bottom/ arbitrary
Alkene + mCPBA = epoxide (include transition state)
ring could have attacked from bottom/ arbitrary
epoxides + base =
SN2 (due to steric hindrance) ring opening/ good nucleophiles at the least hindered position
In acidic conditions, where each substituent goes isn’t as rigid as it is in basic conditions. What product will be the major product and which will be the minor
What reactant can ring open an epoxide to form 1,2 diols
NaOH (SN2 reaction)
What blocks would correspond with this drawing
What is mCPBA (alkene reactions)
electrons from O-H bond to go alkene and double bond goes to that O
What is dihydroxylation of alkenes
-syn addition
-(OsO4)
What is the structure of OsO4
OsO4 makes 1,2 diol
OsO4 makes 1,2 diol
OsO4 is used to make 1,2 diols, but is toxic and expensive. A catalytic variant was developed using N-methylmorpholine N-oxide (NMO) to oxidise the Os(VI) back into Os(VIII) which means the OsO4 is reusable. What is the structure of NMO
OsO4 + alkene =
1,2 diol
1,2 diols can be oxidised (into their ketones and break the C-C bond) with what reactant
▪ Can also use lead acetate, Pb(OAc)4, which is known as a Criegee oxidation
mechanism for making 1,2 diols (cyclic electrons)
What reactants can be used to turn an alkene into 2 aldehydes
NaIO4 and O3
O3 is a good oxidant and can turn an alkene into its ketones. What are the products of this reaction
What is the structure of the O3 reactant
What is the mechanism for an alkene reacting with O3 (cyclic electrons) and then Me2S to make its subsequent aldehydes
SMe2 basically takes one of the oxygens away
Alkene reacting with O3 and Me2S can make its aldehydes, but Ozonide can also be reacted with other oxidants to create other products. What do these make
54
How to go from an alkene —> acid
O3, H202
How to go from an alkene —> aldehyde
O3, Me2S
How to go from an alkene —> alcohol
O3, NaBH4
What reactant forms chloropropanes from alkenes
addition of carbenes to alkenes
what are alkynes
triple bond
What are the table trends (s-character means the anion [made when deprotonation] is closer to the nucleus and therefore has greater stability)
Alkynes are deprotonated to give anion in an sp-hybridised orbital
table and answer in photos
what is a terminal alkyne
carbon-carbon triple bond is at the end of the carbon chain
Why do alkynes have a lower pKa than alkanes and alkenes
alkynes are easier to deprotonate because their anions are more stable/ have higher s character
What can be used to deprotonate a terminal alkyne
strong base (must be pKa >25 for complete deprotonation) /bases attack hydrogen
1,2-Dibromoalkanes can be used to make alkynes, also with a strong base with two E2 reactions. What is the mechanism for this
What is NaOt-Bu
which will be the stronger base/ could be instead of NaOt-Bu
Alkynes + water and strong acid —->
ketones
What is the mechanism
makes most stable carbocation
like other alkenes, alkynes can undergo hydroboration. What dictates where the Boron adds to and what must the boron have in order for this reaction to go ahead instead of side reactions
least hindered end
Hydroboration of terminal alkynes to give aldehydes requires a sterically demanding borane to avoid side reaction
What are the conditions for hydrogenation/ adding to H to any alkene/ alkyne to make an alkane
hydrogen and a palladium/ carbon catalyst
Hydrogenation of alkynes will go to completion at an alkane. How would you stop it an alkene
H with poisoned palladium catalyst/ Poison reduces the activity of the palladium and prevents further reduction
What is the most popular palladium catalyst poisoned with lead
Lindlar’s catalyst
hydrogenation of an alkyne is a syn addition and will therefore lead to a (Z) alkene. What conditions do you do the reaction in to leave to the (E) isomer instead
dissolving metal conditions/ Birch reduction (radical chemistry and makes single electron)
What is the mechanism for this
A more substituted molecule on the C with the leaving group will undergo faster/slower E1 elimination
faster
What types of molecules can undergo E1
tertiary and some secondary
What type of molecule will always be the fastest in E1 AND E2 eliminations
tertiary, secondary then last primary
Examples of strong bases
OH-, n-BuLi, NaNH2,
Examples of weak bases
NH3, CH3NH2
weak base = strong conj acid
Which will be the strongest base/ what factors effect how strong a base is
base accepts a proton; CH3- because it is the least stable.
1) Across the table (C,N,O,F) EN increases, so F will be the most stable as it wants the electrons close to it and less available for the reaction
2)Down periodic table polorizability increases so stronger bases
Will F, Cl, Br or I be the best base
Flourine is the best base as it is least stable- Iodine is the most stable as charge is more stabilised as it is concentrated in the largest area
Which anion is the most stable
Is acetone polar protic/polar aprotic
polar aprotic
