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Author: Subject: Synthesis of N-(1,1-Dimethyl-2-phenylethyl)acetamide
EvlRenne
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[*] posted on 9-11-2018 at 03:47
Synthesis of N-(1,1-Dimethyl-2-phenylethyl)acetamide


Guys, I need your help, I was looking for the information on the web, and I failed to find the answer about how to correctly proceed with Ritter reaction.
I want to synthesize N-(1,1-Dimethyl-2-phenylethyl)acetamid and I want to copycat of one guy, he is Russian and my friend translated everything for me.
A little story of mine.
I did buy 2-Methyl-1-phenyl-2-propanol from China and other reagents from local supplier with p.a. purity certificates.
I bought 2-Methyl-1-phenyl-2-propanol because steps to synthesize it are includes very potent lacrimators and I don't have proper fume hood.
I need your advise, why I can't make desirable amide?
My steps are:
1) to 105ml of acetonetrile I added 45ml of alcohol and drop-vise 53ml of 96% H2SO4 during 40min, moderate stirring and room temp
2) RM slowly became pale yellow (Russian's guy RM is dark-red)
3) I left it for 1.5h with moderate stirring / room temp
4) I added 105ml of d.H2O
5) RM now cloudy (suspension) and started to form 2 layers
6) I left RM without stirring for 40min, upper pale yellow level was removed, washed with brine and placed to freezer to crystallized desirable amide
7) After night in the freezer RM still liquid without a trace of crystallization
RM has distinct acetic (vinegar-like) smell.
Should I blame China or my own hands?

[Edited on 9-11-2018 by EvlRenne]
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Waffles SS
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[*] posted on 9-11-2018 at 06:38



Quote:

To a mixture of 2-methyl-1-phenyl-2-propanol (1.5 g, 10 mmol) and acetonitrile (3 mL) in acetic acid (15 mL) was added concentrated sulfuric acid (3 mL) dropwise at room temperature. The mixture was stirred at 65° C. for 3 hours and then poured into ice-water (ca. 200 mL). The aqueous solution was basified with saturated aqueous sodium hydroxide until pH>11. The suspension was stirred for further 0.5 hour, and then the precipitated solid was filtered and washed with water. The white solid was air-dried to give N-(2-methyl-1-phenylpropan-2-yl)acetamide (1.5 g, 78percent yield)

Pathway Therapeutics Inc. - US2012/252802



[Edited on 9-11-2018 by Waffles SS]




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EvlRenne
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[*] posted on 9-11-2018 at 07:16


Quote: Originally posted by Waffles SS  

Quote:

To a mixture of 2-methyl-1-phenyl-2-propanol (1.5 g, 10 mmol) and acetonitrile (3 mL) in acetic acid (15 mL) was added concentrated sulfuric acid (3 mL) dropwise at room temperature. The mixture was stirred at 65° C. for 3 hours and then poured into ice-water (ca. 200 mL). The aqueous solution was basified with saturated aqueous sodium hydroxide until pH>11. The suspension was stirred for further 0.5 hour, and then the precipitated solid was filtered and washed with water. The white solid was air-dried to give N-(2-methyl-1-phenylpropan-2-yl)acetamide (1.5 g, 78percent yield)

Pathway Therapeutics Inc. - US2012/252802


Hmm, should I use GAA, if I understood Ritter reaction correctly, water addition is a last step?
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Tsjerk
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[*] posted on 9-11-2018 at 08:04


It is a two step reaction, in the first the mechanism needs a dehydration, in the second you need an hydrolysis.

You used diluted sulfuric acid, don't do this. Use concentrated sulfuric acid and later add water in the work up as Waffles suggested.
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EvlRenne
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[*] posted on 9-11-2018 at 08:19


Quote: Originally posted by Tsjerk  
It is a two step reaction, in the first the mechanism needs a dehydration, in the second you need an hydrolysis.

You used diluted sulfuric acid, don't do this. Use concentrated sulfuric acid and later add water in the work up as Waffles suggested.


Thank you for the answer, I made a mistake, it was my old writings, and my first attempt, where I used diluted H2SO4, after some researches, I used concentrated chemical pure H2SO4.

Can I try Waffles's suggestion without acetic acid? I don't have it atm.
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Waffles SS
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[*] posted on 9-11-2018 at 08:32


all references that i found used AcOH and i suggest to use it.

I just hope you dont use Allylbenzene instead of Dimethyl benzyl carbinol




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EvlRenne
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[*] posted on 9-11-2018 at 08:40


Quote: Originally posted by Waffles SS  
all references that i found used AcOH and i suggest to use it.

I just hope you dont use Allylbenzene instead of Dimethyl benzyl carbinol


Chinese supplier says that it is 2-Methyl-1-phenyl-2-propanol, why Russian guy did not use AcOH?
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[*] posted on 9-11-2018 at 08:50


Quote: Originally posted by EvlRenne  
, why Russian guy did not use AcOH?


Ask him
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EvlRenne
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[*] posted on 10-11-2018 at 00:45


Quote: Originally posted by Tsjerk  
Quote: Originally posted by EvlRenne  
, why Russian guy did not use AcOH?


Ask him

That's not helping at all...

Russians guy post was back in 2001, I was thinking about diluted H2SO4, maybe that's why he used diluted not concentrated H2SO4, CH₃CN + 2 H₂O → CH₃COOH + NH₃, acetonitrile itself with water(from diluted H2SO4?) give us acetic acid
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[*] posted on 10-11-2018 at 01:40


I have no clue about what post you are talking. I understand clear communication is often hard and I also fail in it. But right now I don't know what you are about.
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EvlRenne
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[*] posted on 10-11-2018 at 03:11


Quote: Originally posted by Tsjerk  
I have no clue about what post you are talking. I understand clear communication is often hard and I also fail in it. But right now I don't know what you are about.

I'm trying to synthesize amide as one Russian guy did in the year 2001, in his post the route was:
1) To 2-methyl-1-Phenylpropan-2-ol which he made as C7H7Cl + Mg + Et2O(Anh) + C3H6O(Anh) + NH4Cl and dry it over K2CO3, he obtained 45ml of alcohol as colorless viscous liquid, he added 105ml 2M of acetonitrile and dropwise 53ml 1M H2SO4
3) He obtained dark-red RM which been left for 24h at room temp.
4) He heated RM to 50C on water bath and pour it on 0.5KG of ice
5) He obtained 48.5g of colorless crystals, washed it with water to neutral

Waffles SS wrote up include AcOH, my question was can I do it without AcOH and why Russian guy didn't use it, and why he used diluted sulfuric acid instead of concentrated when Ritter reaction requires strong acid.

Then I found, that hydrolysis of acetonitrile give AcOH, maybe that's why Russian guy didn't use AcOH and used diluted H2SO4


[Edited on 10-11-2018 by EvlRenne]

[Edited on 10-11-2018 by EvlRenne]
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