Quiz 7 Flashcards
describe how acyl chlorides react with organocuprates to form ketones
(unicorn rxn #1)
- unlike grignard reagants, only one equivalent of organocuprate reacts with an acyl halide to produce a ketone as the product
describe the reaction of aldehydes and ketones with acetylide ions
a very weak acid reacts with a very strong base to produce a strong base and strong nucleophile
- the acetylide anions (like grignard reagants) are also organometallic reagants and thus react the same way with aldehydes, ketones, and carboxylic acid derivatives
name the unicorn reactions
unicorn rxn = very very specific to just these solvents
- acyl chlorides react with organocuprates to form ketones
- acyl chloride reduction as the aldehyde
what happens when an aldehyde reacts with an organometallic compound
gives a secondary alcohol with a triple bond still present
describe the reaction of aldehydes and ketones with a cyanide ion
- the overall reaction here is addition of HCN to the carbonyl to form a cyanohydrin.
- must be generated in solution using NaCN and HCl
describe the reaction of cyanohydrins in base, aqueous acid and heat, and with catalytic hydrogenation
Base:
- HO- and H2O (for ex.)
- reversible reaction
- the cyanohydrin reverts back ti the starting carbonyl compound since cyanide ion is also a good leaving group
Aqueous acid and heat:
- HCl and H2O –> AKA H3O+ and heat
- a cyanohydrin hydrolyzes to an alpha-hydroxycarboxylic acid.
Catalytic hydrogenation:
- H2 and Raney nickel
- catalytic hydrogenation reduces the cyanohydrin to a primary amine with an OH group on the neighboring carbon atom
describe the two reactions of aldehydes and ketones with a hydride ion
aldehydes:
- reacts with 1. NaBH4 and 2. H3O+ to produce a primary alcohol
- reduction of aldehydes with H- always gives primary alcohols
ketones:
- reacts with 1. NaBH4 and 2. H3O+ to produce a primary alcohol
- reduction of ketones with H- always gives secondary alcohols
describe reactions of acyl chlorides with hydride ions
- the acyl chloride is very reactive
- reacts with 1. 2NaBOH4 and 2. H3O+to produce a primary alcohol
- reduction of acyl chlorides with H- usually gives primary alcohols as the intermediate aldehyde also is reduced under the reaction conditions
describe how a weak and bulky hydride donor (DIBALH) stops the acyl chloride reduction as the aldehyde
(unicorn rxn #2)
- to stop the reduction of an acyl chloride at the aldehyde stage, you must use H- source that is a weaker nucleophile and sterically very bulky
- an acyl chloride reacts with 1. LiAl[OC(CH3)3]3H, -78 degrees celcius and 2. H2O
- LiAl[OC(CH3)3]3H contains 3 big groups so it can deliver one hydrogen. since only one H is attached, it can’t over reduce
- replacing three of the hydrogens of LiAlH4 with -OC(CH3)3 groups makes it a less reactive reducing agent than NaBH4
- to stop the reduction of an ester at the aldehyde stage, you must use an H- source that is a weaker nucleophile and sterically very bulky
describe reactions of esters with hydride ions
- an ester reacts with 1. LiAlH4 and 2. H3O+ –> esters are less reactive than aldehydes and ketones so it needs a strong solvent
- this reaction produces a primary alcohol
- like acyl chlorides, reduction of esters with H- usually gives primary alcohols as the intermediate aldehyde also is reduced under the reaction conditions
what does DIBALH do
- take an ester and stop it at the aldehyde, the big group helps it not over reduce
- only has one hydrogen separately attached
- the solvent used to stop the rxn
describe reactions of carboxylic acids with hydride ions (reduction)
like acyl chlorides and esters, reduction of carboxylic acids with H- gives primary alcohols as the intermediate aldehyde also is reduced under the rxn conditions
describe the different ways that reductions with H2 can happen
an organic compound is reduce when hydrogen is added to it
1. hydrogen can be added as a hydride ion and a proton (H- with two lone pairs)
2. hydrogen can be added as two hydrogen atoms (two H atoms with one electron each)
3. hydrogen can be added as two electrons and two protons (two electrons (dot-) and two H+’s that are all free floating separately)
what reactants are used for catalytic hydrogenation to reduce carbon-carbon double and triple bonds
solvents that can be used:
- Pd/C
- Raney nickel
- ramey nickel is a very reactive catalyst and is the preferred metal for reducing carbon-nitrogen triple bonds
slide 49
describe how aldehydes and ketones form imines with primary amines
an aldehyde or a ketone react with a primary amine and use a trace acid catalyst solvent to produce an imine and H2O
- reactions are reversible
- use Le Chatelier’s principle to remove H2O and drive rxn to the right
imines vs. amines
An amine is a functional group in which one or more hydrogen atoms are replaced by an alkyl or aryl group. An imine is a functional group containing a carbon-nitrogen double bond.
describe the bonding in an imine
- the pi bond is formed by side-to-side overlap of a p-orbital of carbon with a p-orbital of nitrogen
- the pi bond is perpendicular to the orbitals
describe the formation of imine derivatives
in all instances, imine formation replaces C=O with C=NR
describe how tetrahedral compounds in imine formation are unstable intermediates
- imine formation is reversible because there are two protonated intermediates in the mechanism that can eliminate a group
- imine formation can be pushed to completion by removing water as it’s formed (use of Le Chatelier’s principle)
describe how the pH must be controlled for imine formation
- pKa of ammonium ion is 6 and the maximum reaction with acetone is at pH 4.5
- this difference suggests that for imine formation, the pH should be 1.5 units less than the pKa of the amine nucleophile
- most amines have a pKa of 10.5, so that means the pH of the solution should by 9.0
- there must be enough acid to protonate the oxygen atom of the tetrahedral intermediate so that water can be expelled
- if too much acid is present, however, the amine will be protonated and will not be a nucleophile
describe imine hydrolysis
- acid-catalyzed hydrolysis (H3O+) converts the imine back ti the carbonyl compound and the amine
- the amine co-product is protonated in the acidic solution (not a trace amount), so it is no longer nucleophilic and thus cannot react with the carbonyl compound
- more importantly, the hydrolysis reaction is performed with a huge excess of water, so Le Chatelier’s principle favors the carbonyl compound
describe the reaction of aldehydes and ketones with secondary amines
- a ring with a double bond to an O and a secondary amine react with the trace acid catalyst solvent to produce an enamine
- use le chatelier’s principle to remove H2O to drive rxn to right
what is an enamine
ring with the double bond in the ring attached to the carbon that is attached to N, the N is bonded to R groups
enamine vs imine
imine consists of a C=N double bond while enamine consists of a C-N single bond.
describe enamine hydrolysis
- acid-catalyzed hydrolysis (H3O+) converts the enamine back to the carbonyl compound and the amine
- the amine co-product is protonated in the acidic solution (not a trace amount), so it is no longer nucleophilic and thus cannot react with the carbonyl compound
- more importantly, the hydrolysis reaction is performed with a huge excess of water, so Le Chatelier’s Principle favors the carbonyl compound
describe another way to convert a carbonyl group to a methylene group
(reducing O double bond to just CH-)
- use a Wolff-Kishner reaction
- reagants: NH2NH2 KOH and heat
describe the mechanism for the wolff-kishner reduction
- the ketone forms a hydrazone for the imine formation
- hydroxide removes a proton from the weakly acidic NH2 group
- reprotonation occurs at carbon
- another deprotonation, loss of N2, and reprotonation forms the product
describe how water reacts with aldehydes and ketones
- forms a hydrate
- most hydrates are not stable and usually revert back to the carbonyl form
- the acid protonates the carbonyl oxygen
- the nucleophiles adds to the carbonyl carbon
slide 65
is there a difference in Keq values for acetone, acetaldehyde, and formaldehyde?
yes, there is a pretty big difference:
acetone has smallest Keq and formaldehyde has the largest
describe how the equilibrium constant depends on the relative stabilities of the reactants and products
the equilibrium constant for reactions involving hydrates and carbonyl compounds is influenced by the relative stabilities of the reactants and products. A more stable product will result in a larger equilibrium constant, favoring the formation of that product, while a more stable reactant will result in a smaller equilibrium constant, favoring the reactant side of the equilibrium.
explain the reaction of aldehydes and ketones with alcohols
an aldehyde or ketone is added with an alcohol and an acid catalyst solvent (HCl) to produce a hemiacetal. the reaction can stop here depending on the alcohol and how much of it is used. then it reacts with the same alcohol and HCl to produce an acetal. use le chatelier’s principle to remove H2O to drive rxn to right
describe the acid-catalyzed hydrolysis of an acetal
- acid-catalyzed (H3O+) converts the acetal back to the carbonyl compound and the alcohol
- requires water in excess
- similar to imines and enamines, the hydrolysis reaction is performed with a huge excess of water, so Le Chatelier’s Principle favors the regeneration of the carbonyl compound
how can cyclic acetals be used as protecting groups
- because acetals are stable under basic reaction conditions, they are often used as “protecting groups” in organic synthesis.
- protecting groups are used to “mask” an otherwise reactive functionality during a reaction. said functionality can then be “unmasked” afterwards
- cyclic acetals are very stable with basic reagents
describe the use of protecting groups in synthesis
- LiAlH4 will reduce the ester to an alcohol, but the ketone group will also be reduced.
- the ketone functionality is protected (masked) as a ketal
describe synthesizing alkenes via the wittig reaction
witig reagents are often drawn as if there is a formal P=C double bond, but they react with aldehydes and ketones like a carbon nucleophile.
- an ylide has the opposite charges on adjacent atoms with complete octets
- the product is an alkene that is a mixture of the E and Z isomers
what is the mechanism for the wittig reaction
- only works with aldehydes and ketones
- strength of the wittig reaction:
- C=C double bond always goes where the carbonyl was in the starting material
- can prepare “anti-zaitsev” type products
describe the synthetic utility of the wittig reaction
- carbonyl reacts with the wittig reagant and (Ph)3P=CH2 which produces the previous carbonyl (now an alkene) but instead of O double bonded it has the end of the solvent group (ex. the CH2). The other product produced is (Ph)3P=O.
- allows you to prepare exocyclic double bonds
- anti-zaitsev
how do you choose the reactants for a wittig reaction
- the ylide should come from the least sterically hindered alkyl halide because of the SN2 reaction that you need to do first with PPh3
where are the electrophilic sites for unsaturated aldehydes and ketones
- the have two electrophilic sites
- the double bond is conjugated so the double bond can move via resonance, giving electrophilic sites.
describe direct addition to unsaturated aldehydes and ketones
- 1,2-addition to the carbonyl carbon affords an unsaturated (allylic) alcohol as the product
describe conjugate addition to unsaturated aldehydes and ketones
- 1,4-addition to the alkene carbon, after tautomerization of the intermediate enol
explain thermodynamic control
- with a weakly basic nucleophile, direct addition is reversible, so the reaction is under thermodynamic control
- eventually goes to the most thermodynamically favored position (the beta carbon). the product of the carbonyl is always the most stable
what do weak bases form under thermodynamic control
- they form conjugate addition products
- all of the products are reversible and go to the beta carbon
describe kinetic control
- reacts at carbonyl carbon, which is a fast and irreversible process
- the product that dorms fastest is the product
- uses a strongly basic nucleophile
how does steric hinderance dictate the product(s) under kinetic control
- direct addition if the carbonyl group has no steric hinderance
- yields an allylic alcohol - conjugate addition if the carbonyl group is hindered
how does nucleophile strength dictate the product(s) under kinetic control
(based on the strength of the solvents)
- direct addition and conjugate addition if the hydride source is weaker (yields a mixture of a direct addition product and a conjugate addition product)
- direct addition if the hydride source is strong (just direct addition product)
reaction of unsaturated aldehydes and ketones with organometallic reagents
organocuperates only give conjugate addition products
what does a strong hydride do to a carbonyl
- reduces the carbonyl
what does a weak hydride do to a carbonyl
- reduces the aldehydes and ketones
what is anti-zaitsev
the least stable carbon is where the substituent attacks (E,Z –> where the Z has big groups pm the same side and is least sterically favorable)
what is a carbonyl group
C double bonded to O
what are acyl groups
C double bonded to O and single bonded to R or Ar and something else
what are the two classes of carbonyl compounds
Class #1: aldehydes and ketones –> does not have a group that can be substituted by another group, thus cannot be replaced by a nucleophile.
Class#2: carboxylic acids and derivatives –> carbonyl groups have a group that can be substituted by another carbon (can be replaced by a nucleophile)
how to determine which class a carbonyl group belongs to
depends on the bascity of the group attached to the acyl group
nomenclature of carboxylic acids
-oic acid
- in systematic nomenclature, the carbonyl carbon is C1 (highest oxidized C). also uses numbers
- in common nomenclature, the carbon next to the carbonyl is the alpha carbon. also uses letters
- if carboxylic acid is attached to a ring, it will be called the ring name followed by carboxylic acid
- ex. cylohexanecarboxylic acid
formic acid
HCO2H
acetic acid
CH3CO2H
propionic acid
CH3CH2CO2H
butyric acid
CH3CH2CH2CO2H
malonic acid
HO2CCH2CO2H
succinic acid
HO2CCH2CH2CO2H
acrylic acid
H2C=CHCO2H
benzoic acid
benzene attached to CO2H
phthalic acid
benzene with CO2H attached in two positions (meta)
what is the nomenclature of carboxylate ion salts
when the molecule is the carboxylate anion, drop the -ic acid and add the -ate at the end with the cation listed first
what is a nitrile
- different type of carboxylic acid derivative
- no carbonyl (C=O) group
- same oxidation state at carbon as other carboxylic acids
- primary amide loses water to make a triple bond –> they are dehydrated, primary amide
what are the characteristics of a carbonyl compound
- for the double bond,
- trigonal and planar geometry
- sp2 carbon atom hybridization
- 120 degree orientation
- has a leaving group
- has two pi orbitals above and one sigma bond in the middle (the double bond)
is the carbonyl carbon an electrophile?
carbonyl carbon is an electrophile, the polarity of the carbonyl group causes the carbonyl carbon to be an electrophile
- partial positive on carbon makes it reactive with nucleophiles
describe carboxylic acid hydrogen-bonding in solution and in solid state
- high bp due to two hydrogen bonds (strong bonds)
what is an acetylide ion
C triple bonded to C-R
