oxidation Flashcards
can alkyl side chains be oxidized
yes
terminal carbon oxidation and w-1 carbon oxidation
oxidized to corresponding alcohol.
terminal carbon oxidation produces a primary alcohol that can either be used in conjugation reactions OR can be oxidized further to aldehyde-> carboxylic acid via ADH and ALDH
w-1 carbon oxidation produces a secondary alcohol that can be oxidized further to ketone via ADH or used in phase 2 reactions
what catalyzes the oxidation of alkyl side chains
MFO system
what catalyzes the oxidation of alcohols
ADH
oxidative deamination occurs on…
primary amines on primary substituted Carbon atom
primary amines on secondary substituted carbon atom
explain oxidative deamination mechanism
primary amines on primary substituted carbon:
oxidized to corresponding alcohol - chemically unstable intermediate (carbinolamine) falls apart to produce aldehyde + ammonia (NH3)
primary amines on secondary substituted carbon - carbinolamine intermediate falls apart and ketone + NH3 produced
what reaction occurs on tertiary alkyl amines
N-dealkylation
in the case of 2 alpha carbons 2 reactions are possible. either top or bottom carbon can be oxidized. unstable intermediate (carbinolamine) is formed which falls apart and alkyl group leaves
reactions possible on tertiary amines
tertiary alkyl amines: N-dealkylation
other tertiary amines (like pyridine) - N-oxide formation
what oxidation reaction is SLOW
oxidation of dialkyl amides
hemi acetal is a ___ metabolite
oxidative
what reaction produces a hemi acetal intermediate
O-dealkylation
explain the mechanism/products of O-dealkylation
produces a chemically unstable oxidative metabolite (hemi acetal) that falls apart spontaneously to produce the corresponding ALCOHOL + aldehyde
what reaction produces sulfone
sulfoxidation of thioethers (sulfides).
sulfides are first oxidized to sulfoxides (reversible) and then sulfoxides are oxidized to sulfone (IRREVERSIBLE in most cases)
what reaction produces hemithioacetal
the oxidation of a sulfide with 1 R group being methyl
this is VERY UNSTABLE – even more unstable than hemiacetal because S is a good leaving group
explain the oxidation of thioethers with 1 R group being methyl
The C in methyl is the alpha carbon which gets oxidized to its corresponding alcohol.
this forms a HIGHLY UNSTABLE hemithioacetal intermediate which falls apart to produce formaldehyde + thiol (sulfhydryl)
explain the oxidation of nitriles
no direct oxidation on Cyano group (c triple bond N) in humans, but it is possible for the microorganisms in the gut
if there is another carbon attached to the cyano C with at least 1 available hydrogen, oxidation is possible and a cyanohydrin intermediate is produced. produces CYANIDE + corresponding aldehyde
CYANIDE IS TOXIC
cyano groups are allowed in drugs if hydrophilic enough (acetonitrile) CH3-C triple bond N
once carbons start being added it becomes a problem
explain the mechanism of oxidation of carbon-carbon triple bond
oxidized to a hypothetical intermediate, hydride shift and then a ketene is formed.
reacts with water to produce corresponding carboxylic acid
what structures undergo N-hydroxylation
aromatic amides
barbiturates
others
how many possible choices are there for N-hydroxylation on barbiturates?
are they both likely to occur?
2 possible choices, but it is likely that only 1 will occur because the purpose of phase 1 is just to introduce a polar functional group
AR-NH2 is likely to undergo N-hydroxylation
what is a very important consideration
if the aromatic ring is 2 or more fused rings. the NITRENIUM ION is produced because there is enough stability to keep it there
AR-N+-H
potent carcinogen
explain the reactions possible for carbon carbon double bonds
cis olefin will be oxidized to produce cis epoxide
trans olefin will be oxidized to produce trans epoxide
these epoxides are CHEMICALLY REACTIVE so we dont want them floating around for too long,
therefore, they are hydrolyzed by epoxy hydrase to produce DIOL
explain the oxidation of aromatic systems
arene oxide formation. arene oxide is CHEMICALLY REACTIVE and can be intercepted by arene oxide hydrase (epoxy hydrase) to form a dihydro diol.
then, dihydro dehydrogenase removes the 2 H’s to form a stabilized DIOL
OR
arene oxide can undergo further reactions to produce PHENOL (para mostly) if the R substituent is electron donating
which has weaker activation energy – C-H or C-D? what does this mean?
C-H is weaker so that bond is clipped in the NIH shift demonstration
where is a likely place for hydroxylation?
at the benzylic carbon (carbon attached to aromatic ring)
can azo compounds be oxidized?
yes - in aromatic and aliphatic azo compounds, one N can be oxidized to form azoxide
