Sciencemadness Discussion Board - N-Butylamine

N-Butylamine

mario840 - 27-5-2011 at 23:56

Hello

I have successfully prepared n-butylamine. At first i made n-butyl azide from n-butyl iodide (buy) and sodium azide in methanol (procedure from Organics Functional Group Preparations by Stanley r. Sandler instead bromide i used iodide also it's better leaving molecule). Second step is reduce azide to primary amine , i started search for easy and convinient method and found reduction with Zn/NH4Cl (Reduction of Azides to Amines or Amides With Zinc and Ammonium Chloride as Reducing Agent). So i started my last step according to this method i should get about 90% yield but i got +- 80% , this is fantastic because some product lost while i destill it to purify and this was my first attempt. This method is simple, very cheap (some method need Pt

) and quick , high yielding ( i reflux for about 30 - 45 minutes to sure that reaction is complete). This reaction is basic for preparation of primary amines from azides but the reduce method is very good and not usual.

References :

"Organic Functional Group Preparations" Stanley R. Sandler

"Reduction of Azides to Amines or Amides With Zinc and Ammonium Chloride as Reducing Agent" W. Lin, X. Zhang, Z. He, Y. Jin, L. Gong, A. Mi Synth. Commun. 32(21), 3279-3284 (2002)

Nicodem - 28-5-2011 at 00:17

It is nice that it worked well for you, but you might consider sharing the experimental as well, so that other members interested can learn something from your experience. In it you should address the key issues of this preparation, namely the issues of product isolation and characterization. How did you separate n-butylamine from ethyl acetate? You give the yield, which leads us to believe that you already characterized the product. So how did you confirmed the identity and purity of the product? n-Butylamine is a liquid at standard conditions, so to characterize it in an amateur setting you would have to derivatize a sample and measure its m.p. (have you checked the m.p. of the hydrochloride?).
For amateur chemists, it is not so much the reaction itself that is an issue, but the isolation and characterization, so you would be most helpful if others could learn from your problem solving approach.

mario840 - 28-5-2011 at 00:54

1. Adding all together in the same ratio of moles like in procedure reduction only multiply everything by x10
2. Heating under reflux at first 30 minutes but i heat just for 15 minutes to sure that reaction is done, so 45 minutes is just fine
3. I do NOT add ethyl acetate !!!! only dietyl ether , n-butylamine and EA have almost the same boiling point so i need something "lower" boiling --- i choose Et2O
4. I filter solution and wash with brine and dry over anh. MgSO4 (couple hours)
5. Evaporate solvent (steam bath) i don't need reduce pressure beacuse i use ether (earlier i smeel stinky dead fishy odor but now it's stronger plus irritating but not like ammonia)
6. Residue is destilling and collecting everything 75C - 79C
7. For sure me that is n-butylamine i made Hinsberg test , so i don't have gas chromatograph but i'm sure that is n-butylamine

mario840 - 28-5-2011 at 00:59

Also i want to add i thought about Gabriel synthesis wich also give me n-butylamine but yields will for sure lower and price in my side phthalimide are crazy

Nicodem - 28-5-2011 at 02:54

Thanks for sharing.
If you are still interested in n-butylamine synthesis, you can try the Delepine reaction and compare the results (n-butyl iodide is a primary alkyl halide, thus amenable for this type of amine synthesis and hexamine is OTC in most parts of the world).

mario840 - 28-5-2011 at 04:16

Thanks men for that reaction. I read about this Delépine reaction and seems to be cheaper , only need n-butyl iodide and urotropine , chloroform and ethanol with conc. HCl (these all is still cheaper of NaN3, Zn and NH4Cl etc.). Also i like in these reaction that forming quaternary ammonium salt is easily to filtrate ("...moderate colubility in water (5%), less in alcohol (0.5%) and less still in chloroform (0.08%) and ether...), so we don't need playing with destillation , great plus is that amine (n-butylamine) will be end in HCL form, minus is that this synthesis took longer but i can live with that. I definitely try this procedure. Also they write alkyl iodide react with reasonable speed while bromide and chloride much longer so it's good for me.

g3ovn - 23-6-2011 at 15:20

Sorry my ignorance, but n-butylamine hydrochloride can't be made from n-butyl nitrite reduction with Fe/HCl?

smuv - 23-6-2011 at 16:31

No. With nitrobutane you may have something, but with butyl nitrite, you would probably only get butyl chloride, butanol and maybe some butane, under the conditions you specify.

mario840 - 23-6-2011 at 22:08

n-butyl NITRATE and reduction with zinc/ammonium formate with about 50 - 60% yield, but making n-butyl NITRATE is hard and expensive there are cheaper methods

mario840 - 23-6-2011 at 22:15

Also i made delepine reaction :

-with alcohol as solvent it doesn't work (or have to stay for 42 days to get salt of hexamine TOOOO LONG !)
-it only work in chloroform (12 HOURS boiling - TOO LONG ALSO !)
-filtrate salt and make slurry in alcohol add conc. HCl to disolve salt and boil 30 minutes , chill in ice and NH4Cl get out from solution
-filter , evaporate to dryness and get n-butylamine*HCl, but massive impure
-disolve in water add 45% NaOH and extract with ether
-evaporate ether and get amine
-for puryfy destill at 77-78C

THIS method is usless , only it work at good speed to 3 atoms chain , so n-propylamine we will get in 5 hours boiling

g3ovn - 23-6-2011 at 23:30

Oh, thanks for sharing it!

I think reacting butyraldehyde with ammonia, and then reducing the imine will work also...

mario840 - 25-6-2011 at 08:45

Maybe Gabriel synthesis work faster then Delepine with 4 carbon chains, phtalimide is expensive but make easily from anhydride and ammonia

smuv - 25-6-2011 at 10:12

Quote:

n-butyl NITRATE and reduction with zinc/ammonium formate with about 50 - 60% yield

Really? Do you have a ref, I would not expect this to work. Again with nitrobutane, yes but not with butyl nitrate.

mario840 - 25-6-2011 at 11:03

This is simple procedure , it work with many nitroalkanes :

Zinc-Catalyzed Ammonium Formate Reductions: Reduction of Nitro Compounds
By D. Gowda, B. Mahesh, & G. Shankare, Ind. J. Chem. Sect. B, 40, 75-77 (2001)

there are many others method like : zinc/hydrazinum formate and magnesium/hydrazine formate but these require inert atmosfere like nitrogen , the zinc/NH4COOH or if you read that also 90% formic acid work ! don't need nitrogen

mario840 - 25-6-2011 at 11:06

you have right only with nitrobutane

g3ovn - 25-6-2011 at 20:56

Quote: Originally posted by mario840

phtalimide is expensive but make easily from anhydride and ammonia

I made from phtalic anhydride and urea.

50g phtalic anhydride and 10g urea. Place it in an oil bath at 130-145°C it first starts to
melt, then it "boils" and condenses the phtalic anhydride in the flask.
Suddenly it froths up like 3 times (like in Vogel). Then i take it out the heat, waited a little and put 80mL of dH2O, filtered, and washed with cold water (solubility 1g/1L) until i coldn't smell any more ammonia from the water. Place it in water bath for 2h. The yield was 45g. It can be recristallized from lots of methanol, Vogel says 1200mL for 86g

.
Store it in the dark.

[Edited on 26-6-2011 by g3ovn]

[Edited on 26-6-2011 by g3ovn]

jon - 25-6-2011 at 23:20

sir, i am very interested in your work with azides.
on paper they look dodgy as hell.
can you offer any real world advice on the handling of organic azides?
i understand they are shock/friction sensitive compounds very labile and reactive.

mario840 - 26-6-2011 at 02:52

Theory doesn't sometimes work in practise, n-butyl azide have relativity high boiling point (about 107 C) so basic safety "gear" like gloves, goggles, clothes to change, work in fumehood or outside works just fine if you have gas mask it's good for you. When you synthsise compound (azide) do not "overheat"; boiling temperature of solvent which you use is just fine (best methanol, ethanol is expensive of course anhydrous like methanol), the next advice is when you destill alkyl azide try to get as close as temperature of boiling compound (not higher) beacuse better is steady and slow destillation then explosion, the best option is destill behind a safety barricade like they write in book, but i doesn't use that. I destill many times much more toxic compund than that so try to not demonize too much some chemical. In file i give you method of preparation of alkyl azides in microwave in short time, they use only temp. 100 C !! so try also do not "overheat", like i said in traditional way of synthesise it boiling point of solvent is just fine. Butyl azide and methanol form a azeotrope (b.p 60 C) so you must have very good reflux condenser, but how to separate them they write in book.

Attachment: microwave azides.pdf (160kB)
This file has been downloaded 2276 times

jon - 26-6-2011 at 12:36

i guess for small scale working without a blast sheild is ok but preparative scale i think it would be a must.
personally i have been cut to shreads with exploding flasks, it was'nt very fun.

g3ovn - 26-6-2011 at 14:38

Quote: Originally posted by mario840

1. Adding all together in the same ratio of moles like in procedure reduction only multiply everything by x10
2. Heating under reflux at first 30 minutes but i heat just for 15 minutes to sure that reaction is done, so 45 minutes is just fine
3. I do NOT add ethyl acetate !!!! only dietyl ether , n-butylamine and EA have almost the same boiling point so i need something "lower" boiling --- i choose Et2O
4. I filter solution and wash with brine and dry over anh. MgSO4 (couple hours)
5. Evaporate solvent (steam bath) i don't need reduce pressure beacuse i use ether (earlier i smeel stinky dead fishy odor but now it's stronger plus irritating but not like ammonia)
6. Residue is destilling and collecting everything 75C - 79C
7. For sure me that is n-butylamine i made Hinsberg test , so i don't have gas chromatograph but i'm sure that is n-butylamine

I didnt got it, in the book you are refering to says 24h in a steam bath for n-butyl bromide!
I think at least 6h for the all the iodide the react. Where do you saw 30 min??

Quote:

distilled behind a safety barricade to yield 40.0 gm (90%) of n-Butyl azide, b.p. 106.5°C

Just for the warnings i think that's too much a risk, even more for 24h of heating (or 6h)

! I think there are more safer, quicker and less expensive reactions... i mean i saw 1L of AR n-butylamine for $85, doing like 200mL of it by that reaction will cost me about that.
But thank you for sharing it! I think i will be trying Gabriel synthesis with n-butyl bromide, potassium phtalimide and sodium hydroxide.

Attachment: 35932599-Organic-Functional-Group-Preparations-Volume-2-Stanley-R-Sandler-and-Wolf-Karo-1971.pdf (1.6MB)
This file has been downloaded 2040 times

[Edited on 27-6-2011 by g3ovn]

smuv - 26-6-2011 at 20:15

Not a problem. A buddy in my lab used to work with azides on a large scale all the time. No great precautions were taken. Never a mishap. I have only prepared a couple of azides (both ~10g); no great precautions, no mishaps.

Don't sweat it.

mario840 - 26-6-2011 at 21:38

g3ovn read more carefully , this is procedure for REDUCING alkyl azide to primary amine ! how to make azide is write in book, Gabriel synthesis is this what i'm thinking about too, delepine is only good for allyl, aryl short carbon chain aliphatic IODIDE so making allylamine is good choice (when i will buy allyl alcohol and HBr acid i will definitly try this one), remeber when you will making Gabriel the final step is better add hydrazine in ethanol reflux that for 1 hour, cool and then add HCl because insoluble phthalhydrazide separetes out, while amine*HCl is in solution that make easily to purify amine of course only NaOH will also work ; and don't forget post your results

jon - 26-6-2011 at 21:54

thanks for the real world advice people.
if your looking for advice on hydrobrominations i've done it hundreds of time on a certain essential oil with 92% yield everytime.
the idea is to make the hbr insitu in acetic acid from sodium bromide and h2so4.
it's easy the less you mess with it the better the result.
i suspect some of my synapses are'nt there anymore as a result.
p.s.
i noticed a burette clamp this is bad lab technique.
use a 3 prong next time, you get better extention and grip that way.

[Edited on 27-6-2011 by jon]

[Edited on 27-6-2011 by jon]

smuv - 26-6-2011 at 23:55

A nice thing about the gabriel is the intermediate substituted pthalimides are easy to purify and generally recrystallize nicely from lots of solvent systems. You can put a crude halide into the gabriel and get out a pure amine. Also, hydrazine isn't necessary for simple amines, extended saponifaction gets the job done (and is how the reaction was originally preformed).

@jon doesn't seem like they were all needed (synapses).

[Edited on 6-27-2011 by smuv]

mario840 - 27-6-2011 at 01:02

Now i regred that i tried delepine reaction ,i should try gabriel, much shorter reaction time for longer chain carbons , it's done even with chloride (delephine reacts for months in room temperature with chlorides) iodide react of course much faster , reaction can be done in dimethylformamide or ethanol (delepine only in chloroform - the first step), there are couple substitutions for phtalimide in this reaction for example : sodium diformylamide is easily prepared from sodium, methanol, formamide (i got everything) but still phtalimide is better option (cheaper)

nannah - 5-2-2014 at 16:33

Im sorry to post in this old thread. I just didn´t wanted to start a new to ask you this question.

I was recently, a couple of days ago offered to buy a couple of different reagents. It wasn´t nothing special, but one out of the half dozen reagents cought m eye. He had n-Butylamine that he wanted just 18 usd for 2 liters. But that can´t be right, right?
Catalyst are usually kind of expencive.

I wanted to ask you first, so can anybody help me out?

[Edited on 6-2-2014 by nannah]

Methyl.Magic - 12-3-2014 at 15:32

Very nice job [clap clap] .

You can also try the hoffman rearrengement by forming pentanamide from pentanoic acid (ayyyyyy !!) and ammonia and treating it with bleach.

Dr.Bob - 13-3-2014 at 06:27

n-butylamine is made industrially on a large scale, so that price is not too unusual, especially if he does not need it. It will also absorb water, CO2, and oxygen from the air to form various crap in it over time, so try to keep the bottle well sealed and may parafilm it. If you want really clean amine, you would need to distill some before use. But n-butylamine is not a catalyst other then as a base for some reactions. Nothing magical about it. But a cheap source of it, I would agree.