Final Exam Flashcards
sulfonates
- So3 groups
- S is double bonded to two oxygens and single bonded to the third oxygen
- very good leaving groups because of resonance
- made from corresponding alcohol in a reaction
alcohols in elimination and substitution reactions
they are bad leaving groups so they get converted into good leaving groups by sulfonates or strong acids
-OH as a reagent
strong nucleophile and a strong base
pyridine
non-nucleophilic base
how is the alpha carbon respresented in sulfonate reactions?
with R
stereochemistry of OH and sulfonate reactions
stereochemistry does not change because the sulfur gets attacked
how are alcohols used as starting materials in reactions?
to make alkyl halides and alkenes
What needs to occur if an alcohol is the reactant?
strongly acidic conditions are needed to protonate OH into H2O because H2O is a good leaving group
HBr as a reagent
strong acid, not a nucleophile or base
Br as a reagent
strong nucleophile only, encourages substitution
HX mechanism for alcohols
- results in a substitution reaction
- primary alcohols react Sn2
- secondary and tertiary alcohols react Sn1
what conditions are protic conditions?
strongly acidic
elimination of alcohols
-favored by H2SO4 because the byproduct of the first step
-favored by heat
-
what do protic conditions favor?
E1 for secondary and tertiary substrates
retrosynthesis
thinking and synthesizing backwards
addition reactions
- opposite of elimination reactions
- pi bonds act as lewis bases, nucleophiles or bronsted lowry bases
- at temperature dependent equilibrium with elimination reactions
- typically add 2 atoms across a pi bond
- usually exothermic
what does 🔼G represent in elimination reactions?
competition between the enthalpy and entropy term
low temperature 🔼G reactions
- entropy is small
- enthalpy dominates
- 🔼G
- K>1
- products favored
high temperature 🔼G reactions
- entropy is large
- entropy dominates
- +🔼G
- K<1
- reactants favored
why are addition reactions usually exothermic?
a pi bond is broken and 2 sigma bonds are formed
enthalpy for exothermic addition reactions
neagtive
entropy of addition reactions
entropically unfavorable(- 🔼S) because 2 molecules become one
how can an addition reaction be favorable if the entropy is unfavorable?
enthalpy magnitude outweighs unfavorable affect of enthalpy
which types of addition reactions are most closely related?
halogenation and halohydrin formation
hydrohalogenation
a reaction where H and a halide are added across a pi bond
hydrohalogenation mechanism
- Proton transfer generates a carbocation
2. nucleophilic attack
rate determining step of hydrohalogenation reactions
proton transfer/carbocation generation step(the first step)
function of an alkene in hydrohalogenation
alkenes function as a base
how are alkenes able to function as bases if they arent basic?
in hydrohalogenation, the acid is so strong that the alkene can play the basic role
characteristics of carbocation intermediate in hydrohalogenation
- flat
- can be attack fromt he top or bottom
- strong electrophile
Markovnikov’s rule
H is added to the vinylic C atom bearing more H atoms, or the less substituted carbon
regiochemistry of hydrohalogenation reactions
pro-markovnikov rule
why is markovnikov’s rule usually executed in addition reactions?
it creates the most stable possible carbocation, which stabilizes the transition state and allowing the product to form faster
What decides the activation energy of a reaction?
the transition state energy level
What stabilizes the carbocation intermediate in addition reactions?
hyperconjugation from the more substituted atom
When does hydrohalogenation result in a racemic mixture?
When a chiral center forms
What decides the regio and stereo chemistry of addition reactions?
the formation of the carbocation
methods of alkene hydration
- Acid catalyzed hydration
- Oxymercuration-demurcation
- Hydroboration-oxidation
acid-catalyzed hydration regiochemistry
markovnikov addition
stereochemistry of acid catalyzed reactions
racemic mixture of products
are rearrangements possible for hydrohalogenation?
yes
are rearrangments possible for acid catalyzed hydration?
yes
regiochemistry of oxymerucration-demercuration
markovnikov addition
stereochemistry of oxymercuration-demercuration
anti addition
are rearrangements possible in oxymercuration-demercuration reactions?
no
regiochemistry of hydroboration-oxidation reactions
anti-markovnikov
stereochemistry of hydroboration-oxidation reactions?
syn addition
are rearrangements possible for hydroboration-oxidation reactions?
no
What do acid catalyzed reactions do to a molecule?
add H2O to a bond by adding H to one side and OH to the other
how is the acid catalyst shown in acid catalyzed reactions
it is shown over the arrow and in brackets because it is regenerated rather than being a reactant
what is also present when H2SO4 is an acid catalyst?
H3O+
how do we know an acid catalyzed hydration has carbocation intermediates?
OH is added to the more substituted carbon of the alkene
Acid catalyzed hydration mechanism
- Proton transfer: alkene is protonated and carbocation intermediate is formed
- Nucleophilic attack: water functions as a nucleophile to attack the carbocation intermediate
- Proton transfer: water functions as a base to deprotonate the oxonium ion and give the product
purpose of the last proton transfer in acid catalyzed reactions
O+ is very unstable and is never the final product
what determines the rate of addition reactions with rearrangement?
carbocation stability
thermodynamics of acid catalyzed reaction
at equilibrium between alkene and addition product
what type of addition reaction do acid catalyzed reactions have the same thermodynamics as?
hydrohalogenation reactions
How can equilibrium be pushed toward addition products and away from alkenes in acid catalyzed hydration?
- Low temp: with a small entropy, enthalpy will dominate and a low temp will make △G negative
- Use dilute H2SO4 and a lot of water: this utilizes LeChatelier’s principle because water is on the elimination side of the reaction
why do acid catalyzed reactions produce racemic mixtures?
their carbocations are trigonal planar and therefore flat
what limits synthetic utility of Markovnikov reactions?
rearrangements produce a mixture of products
what is a solution to the limited synthetic ability of markovnikov reactions?
oxymercuration-demercuration reactions, no rearrangements
Oxymercuration-demercuration mechanism
Part 1-Oxymercuration
1. dissociation of mercuric acetate forming a mercuric cation: OAc leaves Hg+-OAc
- Pi bond attacks Hg+ forming two resonance structures(one with and one without a ring) as intermediates.
Part 2-Demercuration
3. NaBH4 replaces and reduces the HgoAc group
what role does a mercuric cation play oxymercuration-demercuration reactions?
it is an electrophile that gets attacked by a nucleophile(the alkene)
why don’t oxymercuration-demercuration reactions have carbocation intermediates?
in the mechanism, the resulting intermediate is not a carbocation because mercury has electrons that can interact with the nearby positive charge to form a bridge
oxymercuration-demercuration intermediate
2 resonance structures: one with and one without a ring. The lone pairs and + charge switch places in the resonance
Why don’t oxymercuration-demercuration reactions undergo carbocation rearrangments?
The more substituted carbon bears a partial positive charge instead of a full positive charge
types of stereochem in addition reactions
- Anti-addition: Nucleophile is added to the opposite side of the other added group
- Syn-addition: Added groups are added to the same side
What causes oxymercuration-demercuration reactions to undergo markovnikov addition?
the nucleophile is attracted to the more substituted side, resulting in a smaller activation energy barrier and a faster reaction due to the partial positive charge where the nucleophile is added
What happens to an oxymercuration-demercuration rings as a nucleophile gets close?
it opens up
Purpose of NaBH4 in oxymercuration-demercuration reactions
replace and reduce the HgOAc groups with a -H groups via a free radical mechanism, maintaining the stereochem of the starting molecule
which step of oxymercuration-demercuration governs the products?
oxymercuration
Which reaction is used to achieve anti-Markovnikov hydration?
hydroboration-oxidation
Hydroboration-Oxidation mechanism
- Hydroboration: Boron is added to the less substituted carbon
- Oxidation: OH replaces B H2
Similarities and differences between BH3 and a carbocation
Similar because they are both reactive, both BH3 is not asn reactive because it does not carry a formal charge
What process do BH3 molecules undergo and why?
intermolecular resonance to help fulfill their octets, since they have a broken octet. This results ins hybrid B2H6
Bonds in B2H6
- different from bonding in BH3
- bonds are called banana bonds
purpose of THF
stabilize borane(BH3) in hydroboration-oxidation reactions
What is responsible for the anti-mark property of hydroboration-oxidation reactions?
the reagent
reagent for hydroboration-oxidation reactions
BH3●THF
Reasons Boron is added to the less substituted carbon in hydroboration-oxidation reactions
- Electronics: since B is less electronegative than H, the partially negative H attacks the partially positive carbon which adds the H to the more subsituted alkene bond
- Sterics: BH2 and H are added across the double. Since BH2 is bigger, there will be less steric crowding
what do electronegativity differences result in?
dipole moments
intermediate for hydroboration-oxidation reactions
4-membered ring
What do 1 or 2 chiral centers result in with hydroboration-oxidation reactions?
racemic mixtures
What type of mechanism is hydroboration?
concerted
What type of addition do hydroboration-oxidation reactions?
syn-addition
catalytic hydrogenation
addition of H2 across a C=C bond
What happens if a chirality center is observed in catalytic hydrogenation?
syn addition
catalyst for catalytic hydrogenation
H2 with a metal catalyst
purpose of metal catalyst in catalytic hydrogenation reactions
they make the reaction work and progress at a decently fast rate and absorb H atoms
major product of catalytic hydrogenation
alkane
regiochemistry of catalytic hydrogenation
there is no regiochem because H is being added to both side of the pi bond
stereochem of catalytic hydrogenation
syn-addition
where is H2 added in catalytic hydrogenation and why?
the top or bottom bc alkenes are flat
meso compounds
- plane of symmetry
- achiral, even if chiral centers are present within the molecule
heterogeneous catalyst
- catalyst where catalysis takes place on the surface of a solid surrounded by a solution
- does not dissolve in the reaction medium
homogeneous catalyst
- soluble in the reaction medium
- syn-addition
halogenation
- addition of two halogens across a C=C bond
- only practical addition Cl and Br
how do Br2 and Cl2 get partial charges when they are nonpolar?
they are polarizable, so an induced dipole is generated when a nucleophile is nearby and Br2/Cl2 become electrophilic since electrons are repelled by the nucleophile electron density
product of halogenation
alkane with the halogens on it
regiochem of halogenation
no regiochem
halogenation mechanism
- nucleophilic attack: pi bond attack Br, 3-membered ring bronomium ion forms
- loss of a leaving group: Br-Br bond broken
- nucleophilic attack: Cl/Br attacks the partially positive carbons bronium ion in an Sn2 process, Cl/Br add to the opposite side of the other Br/Cl
how is halogenation similar to oxymercuration-demercuration?
they both have a 3-membered ring as a key intermediate
stereochem of halogenation
- anti because the cyclic intermediate has anti stereochem and intermediates decide the products. rings are similar in structure and reactivity
- enantiomers are formed of the inverse stereochem doesn’t end up being identical
why does a 3-membered ring form in halogenation?
- same as Hg
- additional lone pair
- more stable than a carbocation bc of the partial charge compared to the full +1 charge of a carbocation
difference between halogenation and halohydrin
- the nucleophile
- solvents
electron activity of 3-membered halogenation ring
electrophile
nucleophile in halogenation
bromide
halogenation
alkene with 2 anti Br/Cl instead of the pi bond
solvents for halogenation
- inert solvents that aren’t nucleophiles
- CH2Cl-
halohydrin formation
formed when Br2/Cl2 are added to an alkene with a nucleophilic solvent(water, methanol, alcohol)
Halohydrin mechanism
- Bronomium ion forms form Br2 + alkene
- ion is attacked by water
- proton transfer produces neutral halohydrin product
halohydrin formation products
addition of -X and -OH across a C=C bond
regiochemistry of halohydrins
- regioselective because of water attacking the bromonium ion
- OH adds to more substituted group
- transition state with partial positive charge on Carbon that is more stable than a +1 carbocation as nucleophile gets closer
- markovnikov addition
regiochemistry of onzonolysis
no regiochemistry
dihydroxylation
two -OH groups being added across a double bond
How many steps is hihydroxylation?
2
hi hydroxylation reaction intermediate
- 3-membered ring with O
- allowed to fomr by O-O bond
anti-dihydroxylation mechanism
- epoxide formed(3 membered ring with O): unstable O-O bond is replaced
- H is added to the epoxide O through a proton transfer
- nucleophilic attack of water from opposite side in an Sn2 process
- Proton transfer of H2O attached to ring to H2O in solution
peroxy acid
have C-O-O bonds
what is the reason for protonating the epoxide?
make it a stronger nucleophile so it can be attacked
purpose of water in anti-dihydroxylation reactions
nucleophile
why do anti-dihydroxylation reactions need a neutral nucleophile?
the product is not neutral
what makes 3-membered ring intermediate good nucleophiles?
+1 formal charge and ring strain
what products do 3-membered intermediate rings yield and why?
anti products because the nucleophile attacks in an Sn2 fashion
what type of molecule is MCPBA
peroxyacid
reagent of dihydroxylation reactions
peroxyacids followed by H3O+
Syn-dihydroxylation mechanism
- adds across the C=C bond in one concerted step-no intermediate
- converts osmate ester into a diol by adding Na2SO3 or NaHSO3
what is needed for syn dihydroxylation?
KMnO4 and cold temperatures
What type of mechanism is syn-dihydroxylation?
concerted
Ozonolysis process
ozone(O3) reacts with an alkene to form an initial primary ozonide which rearranges to a more stable ozonide. The pi bond is oxidized
reagents in ozonolysis and their role
- a mild reducing agent is used to reduce
- DMS and Zn/H2O
how can you tell if the reactant was a ring in ozonolysis
if the product double bonds are on the same molecule, and there aren’t multiple molecules
process for synthesis problelms
- determine whether the reaction is single or multi-step
- consider the reagents you know and which reactions might bring about the transformation
- determine any relevant regiochemistry and stereochemistry
- be as efficient as possible
what 2 things do you look for when starting a synthesis problem?
whether or no the carbon skeleton changed and whether or not the functional group changed
process for relocating a group in synthesis problems
eliminate then add a group
alkynes as nucleophiles
similar to alkenes because of their 2 pi bonds and electron density
types of alkynes
- terminal: useful for reactions because of their acidic H, some bases will take it
- Internal: sandwiched by R groups
alkyne p orbitals
- 2 p-orbitals
- 2 pi bonds, each in a different plane
Physical properties of alkynes(goemetry and mobility)
- linear
- rigid
- no free rotation
alkyne naming rules
- parent chain must include C-C triple bond
- name subsitutents
- assign a locant giving the C-C triple bond the lowest number possible
- list numbered substituents before parent name in alphabetical order. Ignore prefixes except iso when ordering alphabetically
- C-C triple bond locant is plced just before the parent name or -yne
- higher priority than alkenes
terminal alkyne pKa and meaning
lower than other hydrocarbons, a strong base is needed to deprotonate it
How can you tell if a base is strong enough to deprotonate alkynes?
if its conjugate acid has a higher pKa(25 for terminal alkynes)
common bases that can deprotonate alkynes
- C-
- N-
- H-
What mechanism can be used to prepare alkynes and why?
E2, they need a strong base in excess and an alkane
what is required for E2?
beta H atoms
geminal vs vicinal dihalide
both have 2 Cs
Geminal: 2 halides on the same Br
Vicinal: 2 Halides next to each other on different carbons
NaNH2 strength
very strong base
role of strong bases in elimination
shift equilibrium toward elimination products
What is needed to acquire a neutral and charged alkyne?
Charged: strong base in excess
Neutral: proton transfer from proton source
what does alkylation add?
addition of carbon chains
what does hydrohalogenation of alkynes add?
HX
what does hydration of alkynes add?
H and OH with tautomerization
what does reduction/hydrogenation of alkynes add?
H atoms
what does halogenation of alkynes add?
addition of excess BR2 or Cl2
ozonolysis of alkynes reactions and results
reaction of ozone and water for carboxylic acids
What is required to convert a terminal alkyne to a good nucleophile?
a strong enough base must deprotonate it
why are terminal alkynes converted to good nucleophiles?
create a nucleophile that can react with a methyl or primary alkyl halide
Alkynide ion reactivity
act as bases with secondary or tertiary alkyl halides to cause elimination instead of substitution
alkylation mechanism
- proton transfer first
- alkyne loses H in proton transfer
- results in strong, small, nuc/base that can undergo Sn2 and add what ever group there is to add
- stepwise
why cant the substrate be hindered for alkylation?
E2 will happen
is hydrohalogenation of alkynes mark or anti mark?
mark addition
termolecular equation and when it us used
Rate=k[alkyne][HX]^2
for alkyne hydrohalogenation
What does excess HX result in for hydrohalogenation?
geminal dihalide(add 2 X groups to the carbon)
difference between alkene and alkyne hydrohalogenation
rate equation and excess mechanism
similarity between alkene and alkyne hydrohalogenation
same regiochemistry
does hydrohalogenation of alkynes have stereochem?
no
why can alkynes add multiple X groups in hydrohalogenation?
multiple pi bonds
terminal alkynes as acids
weak acids
is alkyne catalyzed hydration mark or anti mark?
mark hydration
solvent for alkyne acid catalyzed hydration
HgSO4 to compensate for the slow reaction rate that results from a vinylic carbocation
result of alkyne acid catalyzed hydration
mark addition of H and OH across pi bond
alkyne acid catalyzed hydration reagent(s)
H2SO4 and H2O
taumtomer
constitutional isomers that rapidly interconvert via proton migration in equilibrium with one another
tautomers vs resonance
resonance structures are not in equilibrium and the resonance structures are different compounds
tautomerization in acid catalyzed hydration of alkynes
- cant be prevented
- favors ketone a lot because C=O is more stable than C=C
- between enol and ketone
- breaks bonds and moves them around the molecule
what type of chemical reaction is acid catalyzed hydration of alkynes?
acid-base reaction
Is hydroboration/oxidation of alkynes mark or anti mark?
anti mark
result of hydroboration/oxidation of alkynes
an enol that will quickly tautomerize
tautomerization in hydroboration/oxidation of alkynes
-catalyzed by base
difference between tautomerization in hydroboration/oxidation of alkynes and acid catalyzed hydration of alkynes
in hydroboration/oxidation it is catalyzed by a base and in acid catalyzed hydration it is catalyzed by an acid
what happens to the resonance stabilized intermediate in acid catalyzed hydration of alkynes?
it is deprotonated to yield a ketone
Function of OH in hydroboration/oxidation of alkynes
deprotonate enol to generate enolate ion
function of H2O in hydroboration/oxidation of alkynes
protonate enolate ion to generate an aldehyde
hydroboration/oxidation of alkynes reagents and solvents
1) BH3 THF
2) H2O2, NaOH
result of hydroboration/oxidation of alkynes
Add H and BH2 across a pi bond
purpose of bulky borane reagents in hydroboration/oxidation of alkynes
to prevent the second unit of BH3 from reacting with the intermediate and prevent yield of undesirable side products
Hydration of terminal alkynes guidelines
- mark hydration leads to a ketone
- anti-mark hydration leads to an aldehyde
hydrogenation of alkynes reagent and solvent
2H2
Pt
Result of hydrogenation of alkynes
alkane
hydrogenation of alkynes intermediate and explanation
Cis intermediate because of syn addition
What type of catalyst is used in hydrogenation of alkynes?
a heterogenous catalyst
Why cant hydrogenation of alkynes result in chiral products?
2 hydrogens are added to a carbon
How can alkynes be made into cis alkenes?
- a poisoned or deactivated catalyst
- the catalyst will catalyst the frist, but not the second hydrogenation reaction
- syn addition
- lindlar’s catalyst and P-2(NI2B complex)
- gives 2 instead of 4 H
- stops reaction halfway
How can alkenes be made into trans alkenes?
- single radical electron transfer
- NH3(l) solvent
- single electron goes to one side of triple bond, that atom has a pair and other atom is a radical because the 2 bonded electrons split
halogenation of alkynes mechanism
still unknown
products of halogenation of alkynes
both syn and anti addition
how are products of halogenation of alkynes different than alkenes?
only anti addition is observed in alkenes
Ozonolysis of alkynes
- pi system is completely broken
- alkyne carbons are fully oxidized
- for internal alkynes: cleavage followed by addition of water yields carboxylic acids, split down left side of bond but yields symmetrical product
- for terminal alkynes: split down middle of the bond, results in assymetrical product. Cleavage then addition of water results in terminal side being converted into CO2
What is unique about ozonolysis of alkynes?
only way to make carboxylic acid so far
how do free radicals form?
homolytic bond cleavage-one electron goes to each atom
hybridization of free radicals
sp2 hybridized quickly interconverting between sp3 hybridized due to the number of non-bonding electrons
free radical geometry
trigonal planar
free radical stereochem
- flat
- resemble carbocations
- can be attacked from either face
- stereoselective-makes both enantiomers
role of hyperconjugation with free radicals
groups that donate electrons to free radicals will help stabilize it due to hyperconjugation
role of resonance with free radicals
allylic and benzylic radicals are especially stable due to radicals
which radicals are not stablilized by resonace?
vinylic and aryl radicals
relationship between homolytic BDE and stability of the radical
indirect
Relationship between BDE and ability of homolytic cleavage to occur
indirect
why does hyperconjugation stabilize radicals?
more R groups
why are vinylic and aryl rings more uncommon with radicals?
it takes a lot of energy to remove hydrogens from them
most common radical forming mechanism
H abstraction
is resonance or hyperconjugation more stabilizing?
resonance
BDE of weak bonds
low
how do weak bonds react when forming radicals?
- hard to pull off H atom
- leads to unstable intermediate
Radical mechanism patterns
Initiation: no radical to radical through homolytic cleavage
Propogation: location of unparied electron is move about the molecule
Termination: 2 radicals annihilate each other by forming a bond-radical to no radical
Reactions that result in radicals
- Halogenation of alkene: tertiary radical intermediate, X2 and hv
- halogenation of alkene: hv and NBS(to avoid addition reaction), adds Br, radical intermediates with resonance, pi bond doesn’t allow for normal bromination, has resonance which can yield multiple products
- Hydrohalogenation of alkene in the presence of peroxides(ROOR): anti mark, tertiary radical intermediate, O-O bond is radical initiator bc bond is weak
initiators
- required by radical reactions
- can be heat
regioselectivity of radical halogenation
- occurs at most substituted C because that will form the most stable radical intermediate
- bromination is significantly more selective than chlorination
- Cl is regioselective and Br is regiospecific
- Br has 1 major product, Cl has 1 major and 1 minor product
Hammond postulate in radical reactions
- Br has higher preference in secondary halogenation product
- large energy differences in bromination, smaller energy differences in chlorination
- Chlorination is exergonic, bromination first propogation is endergonic
- both endergonic overall
- in chlorination, energy is close to starting material
anti-mark hydrohalogenation of alkenes reagents
Hbr, ROOR
