Organic Fulton Flashcards
Oxidation can be considered as a…. of H2
Reduction can be considered as a … of H2
loss of H2
Gain of H2
Alcohols are oxidised by transition metal oxidising agent such as..
KMnO4 (potassium permanganate)
CrO3 (chromium trioxide)
Na2Cr2O7 (sodium dichromate)
The metals are in high oxidation statesAs the oxidation proceeds, the metals are reduced to lower oxidation states
What is the Jones reagent and what does it do?
Oxidation with Na2Cr2O7(sometimes CrO3) and H2SO4in acetone is called the Jones oxidation
Works best in the oxidation of secondary alcohols
The Limitations of Jones Oxidation
. Over oxidation is a major issue.
. Furthermore, the use of strong acid means this reagent cannot be used on acid-sensitive substrates.
. Chromium has toxicity issues.
. Expensive to get rid of
To oxidise in the absence of water use..
PCC or PDC
The problems with Chromium Reagents
- It is very difficult to separate the chromium residues from the product.
- Chromium is highly toxic so these oxidations are not suitable for use in pharmaceuticals.
- Large amounts of chromium containing waste are produced.
- Cost can be a problem especially if using PCC or PDC on a large (multi Kg) scale.
What is TPAP ?
Therefore what is the driving force of the reaction using this?
a mild oxidising agent which uses catalytic amounts of metal
Driving force for this oxidation is the reduction of Ru (VII) to Ru (V)
Propose mechanism for TPAP oxidation of primary alcohol?
Manganese dioxide (MnO2) is a very mild oxidant (Mn (IV) so it can only oxidise..
Activated Alcohols such as allylic alcohols or Benzylic alcohols.
What is swern oxidation?
what does it use as the oxidant and the activator?
a mild method to convert alcohols to aldehydes.
Uses DMSO as the oxidant and oxalyl chloride as an activator
Draw the sulfur ylide and explain why it is stable?
Because the ylid is resonance stablized it can be formed relatively easy by deprotonation, Sulfur atom has a low energy d-orbital which can accept electrons from carbon.
Advantages od swern oxidation (3)
Disadvantages od Swern oxidation (3)
- Uses only inexpensive reagents.
- Avoids use of metals, so no toxic waste.
- Easy purification as CO, CO2 and Me2S are all gases
and Et3NHCl is water soluble. - Me2S smells (but it can easily be trapped and reoxidised to odourless Me2SO with H2O2).
- The reaction needs low temperatures (-78 oC).
- Not all alcohols / aldehydes are compatible with the
basic reaction conditions.
Why can Dess-Martin Periodinane (DMP) Oxidation oxidise very sensative alcohols?
The Dess-Martin reagent is active under very mild and completely neutral conditions. The iodine wants to be in a lower oxidation state
What is TEMPO, draw it.
how is it stabilised ?
TEMPO is a stable radical
Reagents used to reduce carbonyls (aldehyde, ketone)? and why?
sodium borohydride(NaBH4) —safe and easy to handle, mild. used in a protic solvent, EtOH, MeOH and acid workup
lithium aluminium hydride (LiAlH4) —powerful, potentially hazardous.
in anhydrous orgainc solvent, Et2O, THF. reacts with H2o producing H2 causing fire
more reactive so can also reduce esters and amides
Draw the Mechanism of Borohydride Reduction
Draw Mechanism of LiAlH4Reduction of Esters
Reductive Amination way to make amines is by the reduction of imines.
draw mechanism
the best way to make secondary amines.
Why is NaBH4 a soft nucleophile?
what kimd of additions will it perform?
NaBH4is a source of nucleophilic hydride ions (H-). However the nucleophilic electrons in the B-H bond are diffuse (allow NaBH4to be nucleophilic as rather than basic like NaH) therefore it will perform initial 1,4-additions, then 1,2-additions leading to reduction of the alkene and carbonyl groups.
If we wish to just do 1,2-addition of the hydride (to just reduce the carbonyl) we can add to the reaction CeCl3. This is a Lewis acid which coordinates to the carbonyl carbon activating it to nucleophilic attack. Now the carbonyl group is MOREreactive, the carbonyl now undergoes 1,2-addition with NaBH4.
What is BH3 a good reagent for?
What does it reduce?
BH3is a good reagent for the reduction of unreactive carbonyls
BH3will reduce a carboxylate to an alcohol
BH3will reduce an amide to an amine
BH3 exists as a gaseous dimer B2H6.
How doe we make this easier to use?
Make it a liquid by its complexation with Et2O, THF or dimethyl sulfide (DMS).
What is boranes reactivity dominated by?
its desire to accept a pair of electrons into its empty p-orbital. That means it reacts with electron-rich carbonyls such as those found in carboxylic acids e rich.
The triacylborateis now much more reactive than a normal ester as the lone pair on O donates electron density to the B, reducing the conjugation in the carbonyl group.
How does the reeactive triacylborate further react to finally release the desired alcohol?
The reactive triacylborate can react with more BH3 to form a hydride releasing anionic borate complex. This reacts further with other anionic borate complexes to finally release the desired alcohols.
What is DIBAL-H?
solvent and conditions used?
DIBAL-H is a milder reducing agent than LiAlH4capable of reducing nitriles to aldehydes, reduction of esters to the corresponding aldehydes.
Needs a non-polar solvent (pentane) and cold conditions
Why can DIBAL-H reduce esters to aldehydes?
because the tetrahedral intermediate formed is stable at low temperature. -70
At higher temperature the tetrahedral intermediate collapses to the aldehyde followed by a 2ndaddition of hydride, resulting in reduction to the alcohol.
What does LiBH4 do, and why?
LiBH4, is not as powerful as LiAlH4 and so will not reduce carboxylic acids to alcohols.
What is the Meerwein-Ponndorf-Verley (MPV) Reduction?
a Lewis acid is used to catalyse a hydride shift from an alcohol to a ketone, forming a new ketone and a new alcohol.
The reaction is reversible so an excess of alcohol is used to drive the reaction to completion. If normally Al(Oi-Pr)3 is used (as solvent and reagent) then the resulting ketone is acetone, easily removed by evaporation after the reaction.
What is Ozonolysis and how does ozone oxidise c-c double bonds?
Ozone is a powerful oxidising agent which can cleave carbon-carbon double bonds to produce two carbonyl-containing fragments
First steps are a 1,3-dipolar cycloaddition, followed by a reverse 1,3-dipolar cycloaddition:
What other process is an alternative to ozonolysis?
two step addition-oxidation process is an alternative to ozonolysis.
The yields are often higher for the two step process than for the single step ozonolysis
What is Catalytic Hydrogenation?
Catalytic hydrogenation uses hydrogen gas and a metal catalyst to reduce functional groups, especially alkenes
Most common metals for hydrogenation are Pdand Pt, but Rh and Ru can also be used
What process is Catalytic hydrogenation and what happens?
Hydrogenations are syn-Selective
Alkynes can be Hydrogenated to Alkenes, what catalysts are used and why?
Platinum (Pl) and Palladium (Pd) catalysts are used to reduce alkynes all the way to alkanes.
When the catalyst is ‘poisoned’ with lead, the reduction will stop at alkenes.
The best cataystfor this process is called Lindlar’scatalyst
This reduction is stereoselective–syn-addition to afford thecis-alkene.
Hydrogen can derive from sources other than H2gas.
What molecules can act as H2 donors in the presence of the metal catalyst
Molecules such as cyclohexene, hydrazine or formic acid.
All are oxidised to very thermodynamically stable.
Hydrogenation is the addition of hydrogen to an unsaturated bond.
What is Hydrogenolysis?
Hydrogenolysisis the cleavage of a C-X sigma bond by addition of hydrogen
Because of the need for the substrate to coordinate to the catalyst, only benzylic or allylic C-X bonds will react
What is the Rosenmund Reaction?
What is the reagent and catalyst?
Why is Quinoline added too?
The hydrogenolysisof an acid chloride to give an aldehyde
The Pd is supported on BaSO4(or CaCO3) as it allows products to escape the catayst surface more easily and avoid over reduction.
A tertirary amine is needed to neutralize the HCl produced in the reaction
why is the anion formed in the deprotonation step is relatively stable?
there is donation of electrons into the empty 3d orbital of sulfur
there is donation into the empty σ* orbital on the C-S bond.
REPEAT WITH ANOTHER ALDEHYDE
What is umpolung
This reversal of natural polarity
In the anion derived from 1,3-dithianes, this polarity of the Carbon reversed and is nucleophilic.
In a carbonyl it is electrophilic.
What reagent and solvent is used to remove the 1,3-Dithiane leaving the product?
HgCl2 and H2SO4
mercury chloride
What does Raney Nickel catalyst (Ni/H2) do?
reduce a 1,3-dithiane to a methylene by hydrogenation
when can Nucleophilic Addition to Carbonyls not happen?
When the LG is an alkyl or H as Hydride is a poor LG
In the Cannizzaro reaction, hydride is the leaving group, but this can only happen when..
2 Aldehydes produce..
Reeagents?
There are no alpha H’s (if there are, aldol condensation occurs)
Need I) OH- (Base)
ii) H3O+ dilute acid workup
This produces a Carboxylic acid and an Alcohol
Draw the mechanism for the Cannizzaro Reaction
The most important reducing agent in Nature is NADPH, what does it do?
NADPH functions as a hydride donor in much the same way as the tetrahedral intermediate in the Cannizzaro reaction.
What is Tishchenko Reaction?
the conversion of aldehydes into esters in the presence of a Lewis acid catalyst:
Swern oxidation reagents, conditions?
convert alcohols to aldehydes.
Uses DMSO as the oxidant and oxalyl chloride as an activator
DMP
under very mild and completely neutral conditions.
Small scale
Write out reagents to memorise!
