Part 3

Question 1

is there any metabolic reaction possible on a carbon carbon triple bond?

Answer 1

YES
direct oxidation on carbon carbon triple bond

Question 2

is there any oxidation possible on a carbon nitrogen triple bond?

Answer 2

NO, only in the case of an alpha carbon attached to the carbon nitrogen triple bond

Question 3

what is a “ketene”?
which reaction produces a ketene as an intermediate?

Answer 3

R-C=C=O

direct oxidation of carbon carbon triple bond after the falling apart of the hypothetical oxidative intermediate

ketene reacts with water to produce a carboxylic acid

Question 4

explain the metabolic reaction that Carbon Carbon triple bond undergoes

Answer 4

direct oxidation on carbon carbon triple bond.

oxidation produces a hypothetical very unstable intermediate. Hydride shifts to the left and C=O is formed to produce a KETENE.
when this ketene undergoes reaction with water, it produces the corresponding carboxylic acid

Question 5

what compounds can undergo N-hydroxylation?
is this an oxidation or reduction?

Answer 5

-aromatic amides
-barbiturates
-others

Question 6

on a barbiturate, how many possible N-hydroxylations are possible?

Answer 6

2 are possible, but it’s likely that only 1 will be hydroxylated, because the whole purpose of phase 1 is to just put a polar functional group on the molecule for phase 2 to occur

Question 7

give a potential formula for an aromatic amide

Answer 7

AR-NH-COOH

Question 8

what does zero with a slash through it symbolize

Answer 8

an aromatic ring

Question 9

AR-NH2

what reaction is possible?

Answer 9

N-hydroxylation on either (or both, but not likely) Hydrogens

Question 10

AR-NH2

what is an important consideration with this reaction?

Answer 10

if the aromatic ring happens to be a fused system (2 or more rings) it gives enough stability to a nitrenium intermediate (AR-N+-H) which is a potent carcinogen

HOWEVER this is not likely with just 1 ring (phenyl)

Question 11

what is aniline

Answer 11

aromatic ring with NH2 as the only substituent

Question 12

what phase 1 metabolic reactions are possible on a carbon-carbon double bond?

Answer 12

C=C is a known place of oxidation between carbons

cis-olefin undergoes epoxidation (oxidation) to produce cis-epoxide. similarly, trans-olefin undergoes epoxidation (oxidation) to produce trans-epoxide.
These are stable enough to not undergo a hydride shift, but they are chemically reactive so we don’t want them floating around for too long

the epoxide can undergo epoxy hydrase (a hydrolysis reaction) to produce a DIOL which is reasonably stable

Question 13

how is it that when cis-olefin and trans-olefin are oxidized, you still get cis and trans epoxides, respectively?

Answer 13

there is no time for the intermediate to rotate, so the positions remain the same

Question 14

when is a “dihydroxy metabolite” produced?

Answer 14

through oxidation of a C=C and then hydrolysis reaction on the formed epoxide.
produces a diol with 2 hydroxyl groups

Question 15

what is a olefin group? what is another name for it

Answer 15

aka vinyl group

C=C

Question 16

between….

cyanohydrin
carbinolamine
ketene
the postulated oxidative product of the oxidation of carbon-carbon triple bonds

which is the most unstable?

Answer 16

ketene and postulated product are the MOST unstable.
postulated product is probably the most unstable

Question 17

what are “Arenes”

Answer 17

same thing as an aromatic hydrocarbon. basically just an aromatic ring

Question 18

do aromatic systems undergo oxidation?

Answer 18

YES - ends in phenol formation

1. arene oxide formation can be intercepted and stabilized or go to phenol formation
   (2. Arene oxide hydrase (epoxy hydrase)
2. dihydrodiol dehydrogenase)
3. phenol formation

Question 19

is methoxy electron donating or withdrawing?

Answer 19

OCH3

Electron donating

Question 20

if there are 2 electron withdrawing R substituents on an aromatic ring, is ring hydroxylation to phenol more or less likely?

Answer 20

LESS LIKELY

the more electron donating, the more likely ring hydroxylation will take place

Question 21

besides the ring itself, what is another likely place for hydroxylation in a structure with an aromatic ring?

Answer 21

at the BENZYLIC CARBON