cresol from amino derivative

[hmtlion]

Dear all

Can you suggest a best synthetic procedure for attached reaction.

Regards and Thanks
Hardik

[maks]

Well, if you will lucky may be , acylation of secondary amine by something small like ethylformate so you will receive just this group acylated.
After it converting via diazonium salt produced by t-Buty lnitrite in solvent free procedure into phenol by Sandmeyer reaction. After it deprotection of the side amine

[Phobos]

I don't expect the desired selectivity in protection of secondary aniline vs primary. Your sequence probably would include protection of the primary aniline with some bulky PG1, then protection of the secondary aniline with some PG2, deprotection of PG1, diazotation/hydrolysis and finally deprotection of PG2.
The best way is avoiding of necessary to distinguish between two anilines, and perform the functionalization 1-2 steps before.

[ChemNavigator]

https://patents.google.com/patent/CN101538211B/en

[Phobos]

Ну да, это патент как раз для обычного лабораторного синтеза...
"In the 250ml of zirconium material autoclave, ..."

[ChemNavigator]

Я имел в виду что в резорцинах OH-группы очень легко обмениваются на NH2 (то же относится и к обратной реакции):
https://www.prepchem.com/synthesis-of-3-aminophenol/

[Jokermaniak]

Ну да, это патент как раз для обычного лабораторного синтеза...
"In the 250ml of zirconium material autoclave, ..."

Браслеты переплавить и норм...

[hmtlion]

I am first diazotizing the material with sulfuric acid and nano2, than adding this reaction mass in 70% sulfuric acid @ 120 C. knowing that it will give some impurity of secondary amine. But want to know the trick to separate out the final product by adjusting the pH. Product is forming in the reaction at this temperature but unable to separate out the same. pls advise

[Jokermaniak]

some impurity of secondary amine

Which secondary amine, starting? Mean your product is also a secondary amine.

If so, all your components are secondary amines, acidic extraction wont help. Cresol can be separated from non-phenolic matter by extraction to the strong aqueous alkali (10-20% w/w) followed by acidification, but should be protected from air since such EDG phenolates readily undergo oxidation on air. Or chromatography, as usual...

[ChemNavigator]

Легко окисляются орто-и пара-замещённые (oH, NH2, NHR), мета-продукт должен быть стабильнее.
В случае диазотирования я бы больше переживал за образование на втором азоте N-нитрозамина (который очень неполезен), а также его перегруппировку в кислой среде (NO может слететь с азота и сесть в пара-положение кольца).

[Jokermaniak]

Легко окисляются орто-и пара-замещённые (oH, NH2, NHR), мета-продукт должен быть стабильнее.
В случае диазотирования я бы больше переживал за образование на втором азоте N-нитрозамина (который очень неполезен), а также его перегруппировку в кислой среде (NO может слететь с азота и сесть в пара-положение кольца).

Всё равно, такие феноляты довольно бодро темнеют на воздухе. Видимо за счет общей донорности кольца.

[Phobos]

I would try to obtain with tert-butyl nitrite/p-TsOH selectively the diazonium tosylate from primary amine - may be steric factor is favorable in our case.

[iborohim]

Supposedly if you acylate(say formylate) both nitrogens you can further nitrosate para-nitrogen in alkaline or acidic media by alkyl nitrite or other nitrosating agent to afford nitrosamide which on acidic hydrolysis(involving initial deacylation) should give rise to product. If nitrosamide under acidic conditions is not deacylated, but rather nitroso group is hydrolysed, or migrates to benzene ring, then nitrosation in basic media(in the presence of alcoholate(1eq)) by alkyl nitrite supposedly can lead to cleavage of acyl (after nitrosation) by alcoholate thus resulting in exchange of nitroso and acyl affording diazohydroxyde(or its salt) which on theatment with acid should yield the product.

[hmtlion]

We followed Vogel's Procedure as below; p-Cresol. Use of copper ions in the decompo~ition.p~- ~
Toluidine (5.34 g, 50 mmol) is dissolved in 50 m1 of hot 35 per cent sulphuric
acid and then allowed to cool to below 15 "C. Ice (50g) is added and the
amine bisulphate precipitated. A solution of 4.4 g (64 mmol) of sodium nitrite
in 50ml of ice-water is added dropwise under the surface of the ice-cooled
solution with stirring at such a rate as to maintain the temperature at &5 "C.
After the solution has been stirred for an additional 5 minutes, a few crystals
of urea are added to decompose any excess sodium nitrite. To the cold (0 "C)
solution of the p-toluenediazonium bisulphate is added a solution of 187 g
(775 mol) of copper(11) nitrate trihydrate in 1.75 litres of water. With vigorous
stirring 6.63 g (45mmol) of copper(1) oxide is added to the solution. The
liquid becomes dark blue and rapidly changes to green. About 1 minute after
the addition of the copper(1) oxide the nitrogen evolution ceases and a
negative test with alkaline 2-naphthol indicates that the reaction is complete.
The mixture is extracted with ether and the combined ethereal extracts are
extracted with aqueous alkali. Acidification of the alkaline extract and reextraction
with ether, followed by drying of the ether extract and evaporation
gives p-cresol in 88 per cent yield. But unable to seperate out the material.