Sciencemadness Discussion Board - Is there any way to make 3 amino phenol from salicamide?

Is there any way to make 3 amino phenol from salicamide?

Jackson - 16-4-2019 at 10:26

Is it a possible reaction? I don’t know of any reactions that could do it but I wanted to make sure.

clearly_not_atara - 16-4-2019 at 13:49

Do you mean 2-aminophenol? I'm guessing you could probably pull that off. 3-aminophenol, though... that's gonna be tough, it violates all of the regioselectivity rules.

12thealchemist - 17-4-2019 at 04:44

The Hoffman rearrangement or degradation would work to convert salicamide into 2-aminophenol.

3-aminophenol could be made from phenol without toooo much difficulty - esterify the phenol to phenyl acetate, then nitrate, reduce. The ester group gives meta- selectivity, as opposed to hydroxyl which gives ortho-, para- selectivity. However, you would want to run the nitration with a substantial proportion of acetic acid to minimise hydrolysis of the ester during the reaction. Depending on how you do the reduction, the ester may well hydrolyse in that step; otherwise traditional saponification would work perfectly well.

Jackson - 17-4-2019 at 08:31

Oh dang, could the phenyl acetate be obtained easily by the decarboxcylation of acetyl salicylic Acid?

12thealchemist - 18-4-2019 at 01:42

The only issue is how to decarboxylate acetylsalicylic acid without cleaving the ester linkage - in my experience decarboxylations are done under basic conditions, which are the same for efficient saponifications.

CuReUS - 18-4-2019 at 10:05

Quote: Originally posted by 12thealchemist

3-aminophenol could be made from phenol without toooo much difficulty - esterify the phenol to phenyl acetate, then nitrate, reduce. The ester group gives meta- selectivity, as opposed to hydroxyl which gives ortho-, para- selectivity.

OH is the functional group attached to the ring in pheyl acetate , so it will the one directing the entry of the electrophile in o/p position only.Because of the ester group,you will end up with predominantly p-nitro phenyl acetate,not m-nitro

Quote: Originally posted by 12thealchemist

in my experience decarboxylations are done under basic conditions, which are the same for efficient saponifications.

decarboxylations can be done using just heat too.Also,you need water for ester "hydrolysis",so using solid(fused) NaOH won't cleave the ester

What you could do:

1.Convert salicylamide to benzoxazolone - http://www.sciencemadness.org/talk/viewthread.php?tid=63327#...

2.Nitrate+ring open it to 2-amino,3-nitro phenol -https://pubs.rsc.org/en/content/articlelanding/1896/ct/ct896...

3.remove the amine by diazotisation+reduction - http://www.orgsyn.org/demo.aspx?prep=cv4p0947

http://orgsyn.org/demo.aspx?prep=CV3P0295

(They have used H₂SO₄ and HCl to diazotise the amine respectively,but you can use hypophosphorus acid itself as both diazotising and reducing agent

[Edited on 18-4-2019 by CuReUS]

CuReUS - 21-4-2019 at 00:17

Quote: Originally posted by CuReUS

What you could do:

1.Convert salicylamide to benzoxazolone - http://www.sciencemadness.org/talk/viewthread.php?tid=63327#...

2.Nitrate+ring open it to 2-amino,3-nitro phenol -https://pubs.rsc.org/en/content/articlelanding/1896/ct/ct896...

3.remove the amine by diazotisation+reduction - http://www.orgsyn.org/demo.aspx?prep=cv4p0947

http://orgsyn.org/demo.aspx?prep=CV3P0295

(They have used H₂SO₄ and HCl to diazotise the amine respectively,but you can use hypophosphorus acid itself as both diazotising and reducing agent

better references -

1.https://onlinelibrary.wiley.com/doi/10.1002/ejoc.201101784

2.https://link.springer.com/article/10.1007/s00706-010-0419-9

3.One pot ring opening,diazotisation and reduction by H₃PO₂

chemplayer... - 23-4-2019 at 18:59

Hypophosphorus acid as a one-stop diazotising and reducing agent for the oxazolone ring? That is very interesting - any reference on that would be much appreciated!

Heptylene - 24-4-2019 at 01:38

Very interesting synthesis, and very interesting product too! By ethylation, N,N-diethylaminophenol could be obtained, which is a precursor to many dyes such as Nile red and Nile blue.

CuReUS - 24-4-2019 at 08:13

Quote: Originally posted by chemplayer...

Hypophosphorus acid as a one-stop diazotising and reducing agent for the oxazolone ring? That is very interesting - any reference on that would be much appreciated!

Quote: Originally posted by nlegaux

benzoxazolone is dissolved in 100ml 1M HCl(aq) and heated to 80°C with reflux for 1 hour. The solution is allowed to cool to room temperature and 2-aminophenol is filtered.

Firstly,you will have to open the oxazolone ring using acid.It can be done by H₂PO₂ instead of HCl

As for the one stop diazotisation/reduction -https://ia801907.us.archive.org/31/items/MorrisonBoydOrganic... (pg 797 of pdf , 770 in book)

I made a mistake in my route diagram(the product is 3-aminophenol,not 3-nitrophenol).This is the corrected one -

[Edited on 24-4-2019 by CuReUS]