oxidation

Question 1

can alkyl side chains be oxidized

Answer 1

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

Question 2

what catalyzes the oxidation of alkyl side chains

Answer 2

MFO system

Question 3

what catalyzes the oxidation of alcohols

Answer 3

ADH

Question 4

oxidative deamination occurs on…

Answer 4

primary amines on primary substituted Carbon atom

primary amines on secondary substituted carbon atom

Question 5

explain oxidative deamination mechanism

Answer 5

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

Question 6

what reaction occurs on tertiary alkyl amines

Answer 6

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

Question 7

reactions possible on tertiary amines

Answer 7

tertiary alkyl amines: N-dealkylation

other tertiary amines (like pyridine) - N-oxide formation

Question 8

what oxidation reaction is SLOW

Answer 8

oxidation of dialkyl amides

Question 9

hemi acetal is a ___ metabolite

Answer 9

oxidative

Question 10

what reaction produces a hemi acetal intermediate

Answer 10

O-dealkylation

Question 11

explain the mechanism/products of O-dealkylation

Answer 11

produces a chemically unstable oxidative metabolite (hemi acetal) that falls apart spontaneously to produce the corresponding ALCOHOL + aldehyde

Question 12

what reaction produces sulfone

Answer 12

sulfoxidation of thioethers (sulfides).

sulfides are first oxidized to sulfoxides (reversible) and then sulfoxides are oxidized to sulfone (IRREVERSIBLE in most cases)

Question 13

what reaction produces hemithioacetal

Answer 13

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

Question 14

explain the oxidation of thioethers with 1 R group being methyl

Answer 14

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)

Question 15

explain the oxidation of nitriles

Answer 15

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

Question 16

explain the mechanism of oxidation of carbon-carbon triple bond

Answer 16

oxidized to a hypothetical intermediate, hydride shift and then a ketene is formed.
reacts with water to produce corresponding carboxylic acid

Question 17

what structures undergo N-hydroxylation

Answer 17

aromatic amides
barbiturates
others

Question 18

how many possible choices are there for N-hydroxylation on barbiturates?
are they both likely to occur?

Answer 18

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

Question 19

AR-NH2 is likely to undergo N-hydroxylation

what is a very important consideration

Answer 19

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

Question 20

explain the reactions possible for carbon carbon double bonds

Answer 20

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

Question 21

explain the oxidation of aromatic systems

Answer 21

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

Question 22

which has weaker activation energy – C-H or C-D? what does this mean?

Answer 22

C-H is weaker so that bond is clipped in the NIH shift demonstration

Question 23

where is a likely place for hydroxylation?

Answer 23

at the benzylic carbon (carbon attached to aromatic ring)

Question 24

can azo compounds be oxidized?

Answer 24

yes - in aromatic and aliphatic azo compounds, one N can be oxidized to form azoxide