6c Flashcards
large scale heterocycle manufacture
make the appropriately substituted starting material + form the heterocycle
how are heterocyclic made for new drugs + material discovery
buy the heterocycle + the substitute things at desired positions
describe what is intramolecular cyclisation
when u form a cycle using one starting material.
aka a nuc and an electrophile in one molecule. nuc reacts with electrophile
AB makes Z
describe what an intramolecular cyclisation reaction is when its a concerted process
intermolecular so between 2 different things.
and concerted process so the 2 different ends join at the same time
so AB makes Z
and CD makes Y
intermolecular cyclisation in sequential steps
okay so its intermolecular so its 2 things reacting with eachother to give a big cycle.
and its in sequential steps so its not happening at once.
so u have AB forming Z - this is called coupling
and then after that u have a half connected cycle, so like a semicircle type thing
and then CD form to make Y (this is lowkey giving intramolecular cyclisation bc theyre kinda part of the same molecule)
when u have cyclisation,, what do we normally need to look out for // identify to make sure cyclisation is acc occuring
u need to see if the different molecules have nucleophiles // electrophiles
bc this is how the cycle is gonna be made.
either a molecule with 2 nucs and another with 2 electrophiles.
or 2 molecules with a nuc and electrophile each
reactants must haveeeee
dual reactivity
when a molecule has both 1 nuc and 1 electron,, what could happen and what can we do to prevent this from happening
the molecule can react with itself to form an intramolecular cyclisation reaction.
to prevent this from happening u can make sure the molecule itself is rigid,, preventing the nucleophile and electrophile from reacting.
whats a dual acting electrophil molecule
a molecule that have 2 electrophiles on itself
note down some electrophiles a moelcule can have on it.
this will be attacked by the nucleophile
C=O aka carbonyls
C-OH
c–X (halogen)
CtripleC
CtripleN
alpha - beta unsaturated ketones, aldehydes, esters. ( aka a double bond near the carbonyl functional group.)
how is C–OH an electrophile
the OH is protonated to give water
this is them removed and a carbocation is formed
describe some dual acting nucleophiles aka this is what will attack the electrophiles
NH2
SH
OH
NH2 carbonyl with S instead of an O. the lone pair of the N is conjugated onto the S,, making it an anion which can attack an electrophile
okay so now describe some mixed nucleophiles // electrophiles
NtripleC–NH2
HN=C=S
alkene with R2N on one side and an R group on the other side
NH2 attached near a carbonyl
NHR near a carbonyl
whwhat are the two different ways we can synthesise pyridine
[C5 + N]
[C3 + C2N]
whats the first way u can make pyridine with C5 + N
1-5 dicarbonyl + NH3 + [O]
1-5 dicarbonyl + NH3 + [O] steps to make pyridine: what should we do
look at the end product and label the N of the pyridine 1,, then go clockwise // anticlockwise labelling everything.
then look at the starting materials,, label the N of NH3 as 1 and then look at the carbons its bonded to and label them aswell.
basically just label everything and see what C u need to bond to whatttt
then identify the nucs and electrophiles that will bond to eachother to form the product
1-5 dicarbonyl + NH3 + [O] mechanismmmm
NH3 attacks the carbonyl anf makes the carbonyl O become a OH.
the NH2 then attacks the other carbonyl also forming OH.
the lone pair on N is used to kick off the OH, a base then is used to remove a H from the ring to form a double bond and neutralise the N(+).
the N lone pair then kicks off the other OH off. the base then deprotonates the H on the ring and this neutralises the N and forms another bond.
the N still has a H on it tho which needs to be removed for it to be pyridine so we need to oxidise it.
we do this using H2O2, MnO2, Ce4+ or O2
okay how do we make pyridine using [C5 + N] but the Hantzsh way
u have 2x 1-3 dicarbonyls, one formaldehyde + NH3
once again look at the final product
