Quiz 6 Flashcards
when does a carbon act as a nucleophile vs an electrophile
carbon is an electrophile when it is attached to an EWG (ex. halide)
carbon is a nucleophile when it is attached to a metal (ex. Li, MgX)
why does carbon act as an electrophile?
carbon is more electronegative than Li or Mg
what is an organometallic compound
part organic, part metal. contains a carbon-metal bond
what are two of the most common organometallic compounds
organomagnesium and organolithium
explain organolithium compounds
require two equivalents of Li metal and one equivalent of alkyl / aryl halide
very strong bases and excellent nucleophiles
explain organomagnesium compounds
- these compounds are called Grignard reagants
- compounds require one equivalent of Mg metal and one equivalent of alkyl / arenyl / aryl halide
- they are very strong bases and excellent nucleophiles
describe grignard reagants
RMgX
- R can be anything (primary, secondary, or tertiary alkyls, alkenyl, or aryl)
- X can be Cl, Br, or I
what is the solvent for a grignard reaction
Mg and ethers (or THF)
ethers are the usual solvents due to their unreactive nature. the solvent provides electrons so magnesium can complete its octet.
how do organomegnesium and organolithium compounds react
they react as if they were carbanions
- carbon is more electronegative than Li or Mg
- carbanions (hence, Li or Mg, are great nucleophiles).
how do organomagnesium and organolithium compounds react with a proton of an acidic group
- when the grignard reagant or any other organometallic compound reacts with a proton source, it forms an alkene.
- ex. CH3MgBr + H2O –> CH4 + HOMgBr
- organolithium and organomagnesium compounds react violently with water and alcohols, so you must exclude protic molecules or add them to a reaction very slowly / carefully.
explain organocuprates
- also called gilman reagants
- R2CuLi
- undergo coupling rxns to link any two alkyl, aryl, or vinyl groups together
what occurs in an organocuperate rxn
a coupling rxn joins two CH containing groups. the alkyl group of an organocuprate replaces a halogen
what happens to the configuration of the double bond for organocuprates
the configuration is retained
what R group of an alkyl halide and the organocuprate can be used?
- the R group of the alkyl halide (and thus the organocuprate) can be primary, methyl, aryl, vinylic, or allylic
- the R group cannot be secondary or tertiary because of steric reasons
describe the suzuki rxn
- palladium-catalyzed cross-coupling reactions
- both reactions replace the halogen of a vinylic halide or an aryl halide with a carbon-conatining group
describe the first step of the mechanism for the suzuki rxn
- both rxns start by adding palladium between the alkyl group and the halogen
- ex. R-X + PdL2 –> an X shape with Pd in the middle, two Ls on top, an R on the bottom and an X on the other bottom side.
what are the steps of the suzuki rxn
- oxidative addition –> palladium inserts between the R group and the halogen (causes Pd to be oxidized from 0 to 2+ (II))
- involves hydroxide displacing the halide ion
- transmetallation, which is where the R group is transferred from the boron to the palladium.
- reductive elimintion, which is where the Pd II is reduced to Pd 0 and a new carbon bond is formed
(cyclic method)
describe oxidation
C-H bond broken and C-Cl bond formed
an increase in the number of carbon-heteroatom bonds, and/or a decrease in the number of carbon-hydrogen bonds.
describe reduction
C-Cl bond broken and C-H bond formed
decrease in the number of carbon-heteroatom bonds, and/or an increase in the number of carbon-hydrogen bonds.
rank compounds in order of oxidation level
low oxidation
CH3CH3
CH3OH
CH2Cl2
HC triple bonded to N
CCl4
high oxidation level
describe ether nomenclature
R-O-R
- if both R groups are the same, it is a di(group name)
- if both R groups are different, then name them differently
- if other functional groups are present, the ether part is considered an alkoxy substituent
- ex. dimethoxybenzene
what happens if you use a strong acid to form an ether from a primary alcohol
its a bad reaction
- both E2 alkene and Sn2 ether products are obtained
- there is a superior route (the williamson ether synthesis)
explain the williamson ether synthesis
- an Sn2 reaction of an alkyl halide with an alkoxide nucleophile
- reaction of an alcohol (ROH) and an alkali metal hydride ion (NaH) produces RO- (alkoxide ion) + Na+ + H2
- the less hindered / smaller alkyl group should come from the alkyl halide
what solvent is used to produce alcohols from alkenes
cat. H2SO4 and CH3OH
explain the mechanism for the addition of alcohol to alkenes
C-C double bond is split –> one C gets an OR and the other gets an H
explain how strong acids convert a poor leaving group into a good leaving group
- alcohols must be protonated before they can react
- alcohols and ethers have similarly poor leaving groups (-OH / -OR); thus, ethers must also be protonated before the compounds can undergo reaction
what reagents react to cleave a C-O bond
HBr, HI, and CF3CO2H
(they have to be strong acids)
what happens if an ether is attempted to be activated using another method
- an alcohol forms an intermediate that can lose a proton
- an ether forms and intermediate that CANNOT lose a proton, thus reagents such as PCl3 cannot be used to activate ethers.
describe the mechanism for ether cleavage: SN1 Example
- protonate oxygen (acid protonates most basic atom)
- methanol departs, forming a carbocation
- addition of nucleophile
- if a relatively stable carbocation is formed when ROH leaves, it will be an SN1 reaction if the counter anion is nucleophilic
describe the mechanism for ether cleavage: SN2 Example
- the acid protonates the most basic atom
- the nucleophile attacks the less sterically hindered carbon (smaller of the groups)
- if a relatively stable carbocation is not formed when ROH leaves, it will be an SN2 reaction if the counter anion is nucleophilic.
explain the mechanism for ether cleavage: E1 example
- double bond formation
- reagants: CF3CO2H at 0 degrees celcius
- if a relatively stable carbocation is formed when ROH leaves and the counter anion is NOT nucleophilic, it will be an E1
why are ethers common solvents
they react only with hydrogen halides because of their unreactive nature (easier to perform organic reactions)
describe the synthesis of an epoxide
- see slide show
what is an epoxide
an ether with a highly reactive three-membered ring
why are epoxides more reactive than ethers
- more strained, higher energy epoxide has smaller delta G double dagger for reaction (threshold for it to react is less than a normal ether).
what happens when an acid-catalyzed epoxide ring reacts with water
- epoxides can ring-open via acid catalyzed reaction with water to give TRANS 1,2 diols
- under acidic conditions, protonate the oxygene to make it into a good leaving group
- fast ring opening (even at room temp.) due to strained reactive three-membered ring
H3O+ —> X —-> OH2
describe nucleophilic substitution of an unsymmetrical epoxide under acidic conditions (where does Nu attack)
- the nucleophile preferentially attackes the more substituted ring carbon
why is the more substituted ring carbon attacked for a nucleophilic substitution of an unsymmetrical epoxide in acidic conditions
- less substituted carbon produces a primary carbocation
- more substituted carbon produces a secondary carbocation
- there is a high degree of SN1-like carbocation character in the transition state, which leads to the backside attack of the nucleophile at the tertiary center and to formation of a product isomer that has the -Br and -OH groups
- essentially roots back to carbocation stability
describe nucleophilic substitution of an unsymmetrical epoxide under basic or neutral conditions
- the important factor is sterics, with reaction occurring at the least substituted carbon in the three membered ring
- under basic conditions, the less substituted carbon in the epoxide reacts
why is the more substituted ring carbon attacked for a nucleophilic substitution of an unsymmetrical epoxide in basic conditions
- The more substituted carbon of the epoxide is often more hindered by bulky substituents compared to the less substituted carbon. As a result, the nucleophile finds it easier to approach and attack the less hindered carbon atom.
what are epoxide reaction with grignard reagants best used in for synthesis reactions
- the reaction of organometallic nucleophiles with epoxides is a great way to extend a carbon chain by (at least) two carbon atoms.
why do we use epoxides in synthesis
- carbocation rearrangements can and often do occur during the acid-catalyzed addition of water (helps with more predictable outcomes.
- Carbocation rearrangements can occur during these reactions, leading to different products. By using epoxides instead of alkenes, the formation of carbocation intermediates is avoided.
define a thiol
- capture and bind to mercury
- have a pKa of ~10 (stronger acids than alcohols with a pKa of ~15) –> thiols don’t bond to H bonds as easily as alcohols do
- thiols have lower boiling points than alcohols because thiols do not form strong hydrogen bonds
- prepared via SN2 chemistry
key feature of thiolate anions
thiolate ions are very good nucleophiles and are better nucleophiles in a protic solvent than alkoxide ions.
does the sulfur atom of a thiolate make a good leaving group
the positive charge on the sulfur atom makes it a good leaving group as you regenerate the lone pair
carboxylic acid vs. aldehyde and ketone in terms of leaving groups
C bonded to R and Z and double bonded to O:
- where Z = R or H (ketone or aldehydes) –> Z-group cannot leave
- where Z = OH, OR, X, or NH2 (carboxylic acid) –> Z-group can leave
formaldehyde vs. aldehyde vs. ketone
formaldehyde –> two hydrogens
aldehyde –> a hydrogen and an alkyl / aryl group
ketone –> two alkyl / aryl groups
describe the nomenclature of aldehydes
-al
ex. methanal or hexanedial
describe the nomenclature for an aldehyde on a ring
-carbaldehyde
ex. cyclohexanecarbaldehyde or benzenecarbaldehyde
describe the nomenclature of ketones
-one
ex. propanone or hexanone
what happens when you mix a ketone and an aldehyde
the ketone always wins (the ktone is named “oxo” when a second group has higher priority)
ex. 4-oxopentanal (ketone + aldehyde)
describe an acyl group
C bonded to an R group and double bonded to oxygen
describe an acetyl group
C bonded to CH3 and double bonded to O
describe a formyl group
C bonded to H and double bonded to O
describe a benzoyl group
C bonded to benzene and double bonded to O
describe how carbonyls are electrophiles
the carbonyl group in an all carbonyl-containing molecule can be polarized. the partial positive charge on the carbon makes the carbonyl more electrophilic and this the carbonyl can be attacked by nucleophiles. Hence, carbonyl compound has a built in dipole.
tetrahedral intermediate vs. carbonyl compound
they can interchange between each other with the addition / removal of a nucleophile
tetrahedral intermediate:
- sp^3 hybridized carbon
- if it has a leaving group, it’s a carboxylic acid
carbonyl compound:
- sp^2 hybridized carbon
what are the fundamental differences in reactivity between aldehydes / ketones and carboxylic acid derivatives
aldehydes and ketones:
- the -R and -H compounds CANT act as leaving groups in the nucleophilic substitution reactions
carboxylic acids:
- the -OH, -X, -OR, -SR, -NH2, -OCOR, and -OPO3^2- in these compounds CAN act as leaving groups in nucleophilic substitution reactions
what is the difference in how aldehydes / ketones vs. carboxylic acid derivatives interact
- nucleophilic acyl substitution occurs when Y is a group that can be replaced by another group
(ex. compound + Y can produce the compound with Y attached) - in a carboxylic acid derivative, Y- can leave to reform C=O (literally the opposite of the previous)
what is the mechanism for a carboxylic acid derivative
carboxylic acid derivative (C double bonded to O and single bonded to Y and R) —Nu—> (C double single bonded to O, Nu, Y, and R) —–> (C double bonded to O and single bonded to Nu and R + Y)
Y = -OR (ester), -Cl, NH2, or -OCOR
what is the mechanism for a aldehyde / ketone
(C double bonded to O and single bonded to two Rs) —Nu—> (C single bonded to two Rs, O, and Nu) —HA—> (C single bonded to two Rs, OH, and Nu)
explain how some additions of nucleophiles to aldehydes and ketones lead to an addition-elimination product
- addition-elimination can occur when the nucleophile has a lone pair on the attacking atom (O-, N-, or S-)
- water, rather tan the other groups attached to the carbonyl, is eliminated
are aldehydes or ketones more reactive
aldehydes are, with:
most reactive
- formaldehyde
- aldehyde
- ketone
least reactive
why are aldehydes more reactive than ketones
- an aldehyde has a greater partial positive charge on its carbonyl carbon than does a ketone
- an alkyl is more electron donating than a hydrogen atom and thus the carbonyl of a ketone is less positive
- ketones have a greater steric crowding in their transition states, so they have high energy transition states (harder to form) than aldehydes do.
- the carbonyl carbon of an aldehyde is more accessible to a
nucleophile
- the carbonyl carbon of an aldehyde is more accessible to a
which are more reactive: aldehydes / ketones or acyl halides / anhydrides
acyl halides / anhydrides
which are more reactive: aldehydes / ketones or carboxylic acids / amides / carboxylate ions
aldehydes / ketones
how can a new carbon-carbon bond be formed
the grignard reaction
- grignard reagants (organometallics) react with aldehydes, ketones, and carboxylic acid derivatives
- tetrahedral intermediate is produced bu it doesn’t have a good leaving group
- alcohol product is obtained
describe how grignard reagants react with carbon dioxide to form a carboxylic acid
- the carboxylic acid has one more carbon than the grignard reagant
- 1 carbon reactant + 3 carbon reactant –> 4 carbon intermediate —> 4 carbon product
why are numbers used in the reactants for grignard reagants
the reagants are added stepwise, e.g. aqueous acid is not added until the Grignard reagant has reacted completely with the carbonyl compound
when a reaction creates an asymmetric center from achiral reactants, what happens
a racemic mixture is produced
what happens when esters react with grignard reagants
One of the Os (the ester O thats not double bonded) is taken away and replaced with one of the R groups
forms tertiary alcohols
- two equivalents of grignard reagant are consumed which means that two of the R groups in the tertiary alcohol must be the same (CH3)
what are the reactants for the williamson ether synthesis
alcohol-R
halide-R
**R group on halide must be smaller
for williamson ether synthesis, what is the rxn
two reactants become one product (O is broken apart)
what type of reaction is williamson ether synthesis
SN2
what are the reactants for the acid-catalyzed reaction and which rxn type goes with which
HI, HBr, or CF3CO2H
Sn1 and SN2 –> HI and HBr because of the strong nucleophile
E1 –> CF3CO2H because of the weak nucleophile
for acid-catalyzed reaction, what is the rxn
one reactant becomes two product (O is split apart)
for acid-catalyzed reaction, which product gets the halide and which product gets the hydrogen (in the form of an alcohol)
the more stable carbocation gets the halide (both OH and halide attach at the end)
SN1 rxn
- 2 step, carbocation
- stability is important
- rearrangement can occur
SN2 rxn
- 1 step, concerted
- sneaky
E1 rxn
- 2 step, carbocation
- stability is important
- rearrangement
- weak Nu
how to differentiate between elimination and substitution
elimination: double bond form, weak Nu (highly electronegative atom is a poor nucleophile because it is unwilling to share its electrons)
substitution: strong Nu
how to differentiate between SN1 and SN2 (based on structure of compound)
if R is tertiary, allylic, or benzylic, then SN1 because a stable carbocation is formed
reactants for thiol rxn
strong base (ex. NaH) and halide
what type of rxn is a thiol rxn
SN2
what is the configuration of the products for a thiol rxn
sneaky rxn (SN2), so changed around and the stereoisomer is produced (ex. if reactant halide is trans, product with the S that attaches where the halide use to be is cis)
thiol rxn mechanism
R-SH –reactants–> R-S-halide with S replacing the halogen
