Sciencemadness Discussion Board

Carbamate Synthesis

ChemichaelRXN - 29-11-2010 at 18:53

Hi everyone,

I am interested in synthesizing a carbamate, 3-methyl-3-pentanol carbamate, to be exact. Since this is an ester, would I be able to react Carbamic Acid with 3-methyl-3-pentanol, using sulphuric acid as a catalyst, to create my 3-methyl-3-pentanol carbamate product? ...Just how you can react ethanol and acetic acid, using sulphuric acid as a catalyst, to create ethyl acetate...do the same rules apply?

...I hope so!

Anyone know? Thanks for the help!


mnick12 - 29-11-2010 at 20:03

You have carbamic acid?
As I understand it carbamic acid is quite unstable, and certainly wouldn't survive any refluxing. Making carbamates usually requires very nasty chemicals which are often times exceedingly toxic. However if you have access to the proper equipment and chemicals there are a few different routes you can take. Alcohols react with alkyl isocyanates in the presence of a catalyst to from N-substituted carbamates. There is however another procedure which might work the Curtius rearrangement, which involves alkanoyl azides which upon heating (Carefull!) rearrange to isocyantes. Take a look: http://en.wikipedia.org/wiki/Curtius_Rearrangement.

I hope that helps!

watson.fawkes - 29-11-2010 at 21:22

For more information on this substance, see its generic name Emylcamate or its trade name Striatran.

ScienceSquirrel - 30-11-2010 at 04:10

You can prepare it by reacting phosgene with the alcohol and then ammonolysis of the alkyl chloroformate, this is how it would have been done industrially.
Two alternative approaches are here;
http://pubs.acs.org/doi/abs/10.1021/jo01047a033

DJF90 - 30-11-2010 at 04:16

Free carbamic acids are unstable and fall apart, yeilding the free amine and carbon dioxide. Carbamates can be made from the isocyanate and an alcohol, or a chloroformate and an amine, amongst other methods.

DDTea - 30-11-2010 at 10:04

There was some small business that manufactured a catalyst that allowed N-methyl carbamate esters to be synthesized from alcohols and urea. Unfortunately, it's a proprietary catalyst and the guy was very guarded about giving information about it!

But generally, if you want to work with carbamates, you're starting off with rather dangerous reagents (phosgene, methyl isocyanate, etc.) and making a potentially more dangerous, neurotoxic product. The only redeeming value about carbamate poisoning over organophosphate poisoning is that the morbidity isn't as great if you do survive.

EDIT: well, it seems this is a very different kind of carbamate than the kind I was thinking of! Carry on.

[Edited on 11-30-10 by DDTea]

ScienceSquirrel - 30-11-2010 at 16:01

If I was doing it on a small scale I would go for the reaction of the alcohol with phenyl chloroformate to prepare (3-methyl-3-pentyl) phenyl carbonate.
I would then react that with ammonia to make the carbamate. The phenyl group is a lot better as a leaving group so you would get the product in high purity.
This is a literature method for preparing this particular type of carbamate on a research scale so it will be documented with reaction conditions, etc.
As far as I know it is obsolete as a pharmaceutical but I assume that you are making it on a research basis and have access to the reagents and equipment required.

ChemichaelRXN - 30-11-2010 at 22:31

Thanks, I do have information on this compound already. I have the Merck Index as a program on my computer. Here is what it says about Emylcamate:

Monograph Number: 3598
Title: Emylcamate
CAS Registry Number: 78-28-4
CAS Name: 3-Methyl-3-pentanol carbamate
Additional Names: 1-ethyl-1-methylpropyl carbamate; diethyl methyl carbinol urethan; 3-methyl-3-pentyl carbamate; methyl diethyl carbinol urethan; tert-hexanol carbamate
Manufacturers' Codes: Kabi 925; JD-91
Trademarks: Nuncital (Kabi); Restetal (Kabi); Statran (Delagrange); Striatran (Merck & Co.)
Molecular Formula: C7H15NO2
Molecular Weight: 145.20.
Percent Composition: C 57.90%, H 10.41%, N 9.65%, O 22.04%
Literature References: Prepn: DE 245491 (1912 to Chinifabr. Zimmer); DE 254472 (1912 to E. Merck); Melander, Hanshoff, US 2972564 (1961 to Kabi).
Properties: Needles from 30% ethanol, mp 56-58.5°. bp1.0 35°; bp0.7 24°. Slight odor of camphor. Soly in water: 4.0 mg/ml. Freely sol in alcohol, ether, benzene, glycol ethers.
Melting point: mp 56-58.5°
Boiling point: bp1.0 35°; bp0.7 24°
Therap-Cat: Anxiolytic.

_____________________________________________


Anyway, thanks for all the replies! I didnt realize before that synthesizing this compound would be that difficult, and use such dangerous chemicals. Those azides scare me, as well as highly toxic gases.

I want to synthesize this compound for research, correct. I have access to chemicals, but I don’t have any on hand. I can acquire lab chemicals quite easily though, except the more exotic and restricted ones. So far ScienceSquirrel has listed a method that I favour, that doesn’t involve anything too dangerous. Making this compound using this method in a small scale is my goal. I can’t find any literature on the method though. Is there a detailed general procedure for emylcarmate's synthesis or for a similar carbamate that you can share with me? If no please point me in the right direction so I can search and find it. Thanks!

So basically in the method (or correct me if I’m wrong) the 3-methyl-3-pentanol will react with the phenyl chloroformate to make the products of HCl and (3-methyl-3-pentyl) phenyl carbonate. Then the (3-methyl-3-pentyl) phenyl carbonate reacts with ammonia to form the emylcarmate and phenol?
(I am still learning organic chemistry, as you can tell. I love this field of study.)


emylcarmate.jpg - 33kB

ScienceSquirrel - 1-12-2010 at 03:36

This paper has a method and there are references in it to the chloroformate method.

http://pubs.acs.org/doi/abs/10.1021/jo01047a033

Xylitol - 8-10-2015 at 06:07

I am also interested in this synthesis, but I am a beginner and I'd like some clarification before proceeding.

I can't find much info on the chloroformate method, and the link to that research article only once mentions this chemical on the first page, but doesn't actually talk about synthesis.

Would a beginner doing this reaction the more common way (sodium cyanate and triflouroacetic acid) be difficult? I understand these chemicals are very toxic, but is the purification of the final product trivial or do you think it may be hard to remove the toxic products?

The process I would follow is detailed in this patent: https://www.google.com/patents/US3072710
Quote:

Example 1 A mixture of 4.0 g. of 3-methyl-3-pentanol, 5.2 g. of sodium cyanate, 9.1 g. of trifiuoroacetic acid and 50 m1. of tetrahydrofuran is stirred at 45 C. for two hours then neutralized by the addition of solid sodium carbonate. The mixture is concentrated, treated with water and filtered to give 3-methyl-3-pentyl carbamate which has tranquilizing activity.


Also are there any steps you think might be overlooked? Because I'm a beginner I need the most detailed explanation. I'm thinking one thing that might be is the 3-methyl-3-pentanol and sodium cyanate should probably be mixed first with the trifluoroacetic acid added dropwise?

softbeard - 8-10-2015 at 13:07

Fortunately for you, neither sodium cyanate nor trifluoroacetic acid are toxic. Trifluoroacetic acid is a powerful acid and a corrosive/irritant, but that's different. Put another way, the trifluoroacetate anion has a low order of toxicity. Similarly, cyanate has a low order of toxicity. Don't confuse cyanate with cyanide; it's very different.
I can't help you much with your reaction, but if sodium cyanate and trifluoroacetic are all you're adding to your 3-methyl-3-pentanol, I don't think you need worry about poisonous chemicals. Just take standard precautions against irritants, have good ventilation, and wear eye protection.
Let us know how it works out.

Xylitol - 25-10-2015 at 21:12

I performed the reaction and boiled off/evaporated as much solvent as possible. The resulting liquid crystallized. I tried adding hot water and cooling to recrystallize, but nothing seemed to happen, so I just boiled off the water and I'm left with the crystals again. Should I try again with another solvent?

Anyway, I'd really like to know what the by products are in this reaction. Clearly there should be some sodium trifluoroacetate after I neutralized it with sodium bicarbonate. What other by products will form from the sodium cyanate and trifluoroacetic acid?

Texium - 18-7-2016 at 11:18

I was on a wiki walk earlier and came across the ethyl carbamate page. https://en.wikipedia.org/wiki/Ethyl_carbamate

It claims that ethyl carbamate can be synthesized from ethanol and urea and that the reaction is "much faster" at higher temperatures. It does not, however, specify how much faster or how high the temperature has to be, and is unreferenced. Personally, I think it sounds like a load of bunk, but I'm not familiar with the properties of carbamates.

DDTea mentions upthread that a catalyst is required for the reaction, so I suppose that Wikipedia's claim is too good to be true, but I wanted to make sure anyway.