n-butylamine condensations

sony · Fri Mar 11, 2005 11:12 pm

The following compounds where condensed with aprox 1,2 equivalent of nitroethane (one nitromethane attempt aswell) using n-butylamine as a catalyst, the reaction mixture was allowed to drive forward in the dark at RT for a couple of days to weeks. A visibile notice of the reaction progressing is noticed by the formation of H2O as an upper layer.

83,06 g 2,5-dimethoxybenzaldehyde
41,28 g nitroethane
catalyst: 5 ml n-butylamine
reaction time: 3 weeks
yield : 91 g (82 %) recrystalized from MeOH as nice light yellow needles

83,085 g 2,5-dimethoxybenzaldehyde
45,78 g nitromethane
catalyst: 5 ml n-butylamine
reaction time: 4 days
yield : 60 g ( 57%) as dirty carrot small needles.
This very dirty nitrostyrene had to be washed multiple times with IPA and H2O and recrystalized multiple times with IPA and still did not yield a satisfying product.
1,1 equiv nitromethane and 1 ml less n-butylamine would most likeley work a lot better.

62,06 g 4-fluorobenzaldehyde
41,28 g nitroethane
catalyst: 5 ml n-butylamine
reaction time: 2 weeks
yield 70,54 g ( 77,8% ) recrystalized from IPA as shiny long light yellow needles

10 g 2,4,5-trimethoxybenzaldehyde
4,59 gram nitroethane
solvent: 20 ml IPA
catalyst: 1,5 ml n-butylamine
reaction time: 6 days
yield: 3,12 gram (24%) as yellow crystals
After the first crop of crystals where filtered off the rest was accidentally spilled Sad

so the yields where sad

5 grams 2,4,6-trimethoxybenzaldehyde
3,9 gram nitroethane
catalyst: 0,5 ml n-butylamine
reaction time: 16 days
yield: 5 gram (79%) recrystalized from IPA as yellow crystals
No solvent was used this time but gradually more solids started to dissolve, almost al sollids where dissolved at the 4th day and with some swirling everything dissolved. At the 7th day there was 2,34 gram crude nitropropene filtered off and the reaction was left standing for another 9 days to collect the remaining crystals.

75 gram Benzaldehyde
69,82 gram Nitroethane
catalyst: 3 ml n-butylamine
reaction time: 4 weeks
yield: 96,45 g (83 %) recrystalized from IPA as light long yellow needles
Left this one standing for a bit too long as alot of crystals crystalized out already after 22 days

tetraedr · Fri Mar 11, 2005 11:56 pm

Ethylenediamine diacetate easy to synthesize. It necessary to use about 10% of this.

Condensation of 2,5-dimethoxybenzaldehyde with 1,5 eq. excess of nitromethane or nitroethane gives, respectivetely, 95% and 82% yields after 30-60 min of reflux. You do not need to wait for the weeks!

icecool · Insistent Chemist

Does anyone has some more info about just plain benzaldehyde with nitroethane and n-butylamine?

tetraedr · Wed Mar 16, 2005 1:09 am

In 250 ml Erlenmeyer flask were mixed by turns 18 mL (17.3 g) of benzaldehyde, 22 ml (21.1 g) of nitroethane, 1 mL of AcOH and 1 mL of buthylamine or cyclohexylamine. Refluxed 30-40 min, add 150 mL of hot water, stirred thoroughly, decanted, then add 100 mL of cold water, stirred (with stick) again, obtained yellow crystal precipitate filtered off, washed with big amount of water, then with min. amount of cold IPA, and then, with hexane. Yield – 18.5 g (80%), m.p. about 64-65 grad.

Using the more amount of nitroethane (for example, two volumes excess) lead to increase of yield of final compound (up to 90-95%).

icecool · Insistent Chemist

So you're saying if using more then that SWIY already used you will get even better results?
And what about nitromethane I also read a synthese where nitromethane is used and NaOH as a base it is in vogels organic practicum.
If anyone wants I can post it or does anyone have experience with that method?
And what do you mean with AcOH and what is it's purpose?
And didn't you use a solvent, since that decreases the yield a lot...?

tetraedr · Wed Mar 16, 2005 10:21 am

It is Real description of REAL dream of my Dead Ass. All data were taken from REAL experiments.

I can guarantee, that iy is working only for this substrates. For other cases of this reaction (Henry) - are necessary the OTHER conditions.

AcOH = GAA.

icecool · Insistent Chemist

I do not doubt that it doesn't work.
I was just wondering if you used a solvent...
Since it normally gives bad yields and you got a great yield without a solvent then...

IndoleAmine · Dreamreader Deluxe

Tetraedr used a big fat excess of nitroethane, and in this case it also acts as a solvent.

AcOH is acetic acid, I think he meant GAA here. Its purpose is to create neutral conditions (or buffering the amine catalyst, so to speak).

methylamine is the fastest catalyst for plain P2NP, followed by EDDA - but I think the experiment described by tetraedr uses in fact in situ formed butylammonium acetate (or cyclohexylammonium acetate), and the reason for his high yield is not excess of one reagent, but rather short rxn time and the use of a little AcOH...

If aiming for really high yields, you should make some methylammonium acetate, use a solvent which can dissolve this salt (maybe IPA would be a good choice), use 1.1x molar excess of nitroethane to benzaldehyde, and add an inert drying agent like silica gel to take up all water that will form (one mol H2O per mol aldehyde used), and make sure you use enough drying agent. warm slightly for 30 minutes to 1 hour, let stand another 2.5 hours, filter off silica gel and rinse with additional solvent, remove solvent by distillation under reduced pressure, dissolve residue in cyclohexane, wash with H2O and place in freezer to crystallize beautiful P2NP.

Or just use butylamine, ethanol and 1.1x molar excess of nitroethane, and reflux slightly (80°C) for 5-6 hours, then cool in freezer to crystalliez the P2NP, filter off, recrystallize by dissolving in just enough hot IPA and placing in freezer again. Repeat until colour is yellow/white (no orange!!).

The first one is maybe overkill, the second one works still well enough when you consider how little work it is.

And of course EDDA in IPA and stirring a few hours at room temperature, then freezing out and filtering off the P2NP (and rinsing it with H2O) is not really much work, too... Mr. Green

i_a

icecool · Insistent Chemist

SWIM made P2NP today, and he refluxed it for 6 hours and at the end it was dark yellow, slightly orange.
Wouldn't it be dark orange after 6 hours refluxing with a dean&stark trap.
SWIM collected 4ml of water with the following amounts:

17ml benzaldehyde
13ml nitroethane
3,3ml n-butylamine
33ml toluene

It first became milk white, then clear, then slightly yellow and darkened until now it is light orange.
Tomorrow SWIM will proceed with the procedure, but he was wondering should he first distill of some toluene to concentrate the mixture, or just put it in the freezer as it is right now?

BTW When do you use ice cold solvent and when hot solvent when purifying crystals?
I get confused...

IndoleAmine · Dreamreader Deluxe

Good work so far, if the color doesn't get darker anymore, its definately finished. Wink

Now just put it in the deep freezer and wait, be patient (see below).

The theoretical amount of H2O that would be produced is 3.03ml, you can calculate it as follows:

- 17ml benzaldehyde means ~17.85 grams
- one mol of bezaldehyde weighs 106.12 grams
- this means that you used about 17.85g / 106.12g/mol = ~0.168206 mol
- we assume that water is being produced in a molar ratio of exactly 1:1 to the amount of benzaldehyde used (this happens exactly when the conversion is 100% complete), this means for each mol of benzaldehyde you'll get one mol of H2O
- H2O has a molar weight of 18 g/mol
- your reaction will generate 0.168206 mol * 18g/mol = ~3.03 grams of H2O

since your toluene was probably a bit wet, and since you probably didn't use a drying tube etc., you collected more water than the theoretical amount calculated...

And now about hot and cold solvents: the trick is that most substances dissolve far better in HOT solvents than in cold solvents. There are very few exceptions to this. When you recrystallize a substance, you use just enough hot solvent to dissolve all of it; then you cool it, and the substance can't dissolve in the solvent any longer and crystallizes out.

So: you have to cool your toluene to make your P2NP less soluble in it, then it will slowly crystallize. You will have to cool it to under 0°C probably, and if it doesn't crystallize after a few hours, eventually you will need to scratch the inner side of your beaker/erlenmeyer etc. with a glass stirring rod, this initiates crystal formation.

Once the crystals have started to grow (with p2np you can sometimes even watch them doing it!!), give it some more hours - the cystals need time to form, and if you are impatient here, you will have to do more work in the end.

So be patient and wait a few hours, and in the mean time prepare some ice-cold isopropyl alcohol to rinse the crystals during ilztering. Then, when you think the crystals have all formed, quickly stir and break up all those crystals, and pour it onto the buchner funnel with the vacuum running full blast, to immediately remove as much toluene as possible, as long as everything is still cold. Rinse sparingly with small amounts of ice-cold IPA, some P2NP will dissolve, but this is OK - since the remainder will be much purer then. Collect the filtrate and rinses, concentrate to 1/2 volume through distillation and cool to <0°C again to crystallize out the remaining P2NP that didn't solidify in the first Xtalization.

Good luck, report back! Very Happy

i_a

icecool · Insistent Chemist

Ok well SWIM put the RB flask in the freezer yesterday night.
And now 8 hours later approx. he checked out the RB flask and what did he see....

CRYSTALS Cool

Anyway there was one big oval shaped big mass of white crystals and there were some crystals floating around it at the top of the liquid.
And he shook the RB flask really hard so the big mass would smash against the walls of the RB flask so it would be the same as scratching the sides.
He will only have time in 10 hours to filtrate it and wash it.
So just to confirm, he will break up the mass then pour it threw the buchner at full vacuum, then with very tiny bits of ice cold IPA he will rinse the P2NP.
And then take the filtrate and rinse it a couple more times with a bit IPA or did you mean water here?
And after that is done what did you mean with the hot IPA won't still quite some P2NP keep being dissolved in the IPA even while it is cold.

EDIT: Just started doubing a bit, wouldn't the big mass just be water?
It does look like frozen water though.
But when I swirl the flask there are crystals on the sides so there did form some P2NP but I dunno about the big mass...

EDIT2: In the morning when I saw the crystals I scratched the sides of the RB flask and then set it back and went away.
And when I came back 10 hours later it had a big mass of yellow crystals in it.
SWIM filtrated them over a buchner filter, and sucked them dry a bit then rinsed them with 10*C water. (mainly to get the crystals out of the RB flask).
Didn't use IPA because he forgot to put it in the fridge and was so happy he finally got the P2NP that he will do the purification later on when the crystals are dry.

EDIT 3:

IndoleAmine · Dreamreader Deluxe

You got it. The water wash of your p2np was right, and the crystals look pretty pure. I would rinse them with a little bit cold IPA (it washes away much impurities, but only very little p2np, so it is a good method of purifying this stuff).

But they still look a little bit wet, I would say!?

If they are bone-dry and crisp and still have the same color, you can use them without purification, IMO.

Although it is always better to do at least one recrystallization....

Place some IPA into a beaker (maybe 15-20ml in your case), place that into a hot water bath, heat the IPA until it almost boils, and dissolve the p2np into it. If not everything dissolves, you can add some more IPA, one or two mililiters at a time - until everything has dissolved. Then let it stand for some ~15 minutes to concentrate the solution just a bit, and place it in the freezer. Filter, wash and dry as usual Very Happy

....

(but before you dissolve any p2np into hot IPA: take a few crystals, maybe 0.2g, and store them. You will maybe need them some day if you have problems with starting crystallization of this substance. Then just throw a few needles into the cold solution, and they will act as seed crystals..)

Good work!

i_a

IndoleAmine · Dreamreader Deluxe

Oh, and nitroMethane and nitroEthane are not the same: if you would use nitromethane, you could use NaOH as catalyst.
But then you wouldn't get 1-phenyl-2-nitropropene, but 1-phenyl-2-nitroethene (or nitrostyrene), and this is useless..

Because if you would reduce it with LAH, you would get phenylethylamine - no phenylisopropylamine.

Now you know two ways to make useless phenethylamine already -

-benzaldehyde+nitromethane --LAH--> phenethylamine
-acetophenone+ammoniumformate+formic --heat--> phenethylamine

.. Very Happy

But nevermind, this knowledge is important too. Remember that mescaline is a phenethylamine for example, as well as you..... Laughing

(really - condensing 3,4,5-trimethoxybenzaldehyde with nitromethane and reducing the trimethoxynitrostyrene with LiAlH4 gives 3,4,5-trimethoxyphenetylamine, a.k.a. mescaline, for example. Idea

... Starting to get the picture? For henry/knoevenagel nitrostyrene condensations like you just did, you can keep in mind: nitromethane->nitroethenes->phenethylamines; nitroethane->nitropropenes->amphetamines Exclamation

)

cheers

i_a

icecool · Insistent Chemist

SWIM told me they are dry now and it is 6,02g for the first crop.
The second crop, he is still working on that:evaporating of some solvent etc.
Will reply back how much the second crop was.

icecool · Insistent Chemist

Okay well time to find 3,4,5-trimethoxynitrostyrene then Very Happy

Damn SWIM didn't know that making drugs was so easy, at least phenetylamines.
There are so many of them that SWIM will be busy with having pleasure with synthesizing those first, that SWIM doesn't want to synthetesize other drugs.
Anyway you just have to get the hang of it before it works.

Anyway SWIM evaporated off quite some solvent and was left with the water that he didn't seperate off because he was too bored to do it...
Anyway he filtrated the next crop which was a little bit more orange like and it was really nice for SWIM to see when pouring IPA threw the crystals that they really changed color from dark yellow to very light yellow.