[kriggy]

Hi guys, I have this exercise from my synthesis class:

In red is the given reagents/intermediate products and in blue are those I should fill in.
Anyway, Im fairly confident in steps 1- 7 with the exeption of the reaction 6 from aniline to benzensulfonylchloride, I have no idea how to get there in one step or if its that the sulfonyl chloride reacts with aniline but then it doesnt make much sence to me due to following steps.

Well, after the oxidation of methylethylamine (9) Im basicaly lost. Im not even sure that product of that oxidation is correct but I did some googling and it seems ok, however, I have no idea what are the reagents (10) and (11). I was thinking that 10 is o-phenylendiamine and then (11) is dehydrogenation to form the 2nd double bond in the final product. But I have no idea how to connect the product (9) with (10).
Maybe I did one or more mistakes in the previous steps but because the methylethylamine is given by my teacher im fairly confident in the first steps (Although I cant find the reagent to get the amine from sulfonamide but it was covered in class briefly but I wasnt able to write it because we moved on)

Im glad for any thoughts / ideas / help
thank you

[discodermolide]

Chlorosulfonic acid will give the benzene chlorosulfonic acid directly.


I shall think about the rest of it.

[discodermolide]

Surely the reagent for 8 is either acid or base, sulfonamide hydrolysis.

[kriggy]

Yes but the starting material is aniline so I dont see how it can be converted to chlorsulfonic acid in one step.
I have to ask my classmates if I didnt do any mistakes when re-drawing the scheme from screen because it doesnt make much sense because it could be done in much lower amount of stepes preparing the brominated ketone should be easy by friedel crafts and then its just one or two more steps or if that wont work I could see the start from styrene and then hydroxylation  by OsO4 or KMnO4 followed by oxidation and then reaction with o-phenylendiamine. It might not be pretty or fancy but its much lower amount of steps. I understand that its exercise but still..
edit:

Surely the reagent for 8 is either acid or base, sulfonamide hydrolysis.

Makes sense thanks

[discodermolide]

Sorry I didn't realise that the SM was aniline, my mistake.
Why did they make it so complicated?

[kriggy]

Sorry I didn't realise that the SM was aniline, my mistake.
Why did they make it so complicated?

I have no idea but I think the point of this exercise is not to find the optimal way to the product but rather to find the best conditions for each separate reaction which somehow ended in this reaction scheme together.

[orgopete]

Chlorosulfonic acid will give the benzene chlorosulfonic acid directly.

That is nearly correct, it should be SO2/CuCl (or something like that). There is an error though, the starting material should have been the diazonium salt (so indirectly from aniline).

[Dan]

I was thinking that 10 is o-phenylendiamine and then (11) is dehydrogenation to form the 2nd double bond in the final product. But I have no idea how to connect the product (9) with (10).

I have an idea but I'm not 100%.

I think 11 is phenylenediamine. Work backwards from that to get a possible structure for 10.

I also think 9 is correct. Its reaction with bromoacetophenone to give 10 is not immediately obvious (but is a logical stepwise process). What's the first reaction you expect to happen on mixing 9 and bromoacetophenone?

[kriggy]

So 10 should be phenylglyoxal.

After your hint I think it could go like this

[Dan]

In essence yes, but there is a step in your mechanism that I think is unreasonable - formation of a monovalent O⁺.

Following S_N2, I would be inclined to form an enamine and then do a concerted intramolecular fragmentation.

[orgopete]

Re: enamine formation

It still requires a proton acceptor. I'd just use that proton acceptor to pull the alpha hydrogen directly. I'm not disagreeing with writing HBr to balance the stoichiometry, but it will protonate the imine. Had the problem used sodium nitrite, a similar mechanism could be written for the oxidation and I'd argue deprotonation is probably intermolecular.

Just a parenthetical question, a number of steps were included to create the nitrone, is a nitrone a better oxidant in this reaction than nitrite? (Or was the instructor just messing with the class without really making a point about the reagents?)

[Dan]

It still requires a proton acceptor. I'd just use that proton acceptor to pull the alpha hydrogen directly.

I did consider that as well, but I expected the proton α to the iminium to be more acidic than the proton α to the ketone so I went for that first.

Just a parenthetical question, a number of steps were included to create the nitrone, is a nitrone a better oxidant in this reaction than nitrite? (Or was the instructor just messing with the class without really making a point about the reagents?)

I was wondering about this too...

[kriggy]

I have no idea about the nitrone/nitrite. I guess he is just trying us if we can find the right reagents / conditions to form the desired product. This exercise is a bit weird because he always showed us very effective ways to make the compound (he is also head of R&D in chemical company) but this realy doesnt look like very effective way to this compound.