03-05-04 08:46
No 493104
So, here is an idea SWID had for making TriEthylAmine.
First, Ethyl Bromide is synthed from NaBr, H2SO4, and Ethanol. No sweat, well documented and optimized, reactants and reagents easily obtained.
SWID ran the balanced equation, and realized that if EtBr was dripped into a ethanol solution saturated with ammonia, the following would probably take place:
3(NH3) + 3(EtBr) => Et3N * HBr + 2(NH4Br)
SWID is hoping that by dripping the ethanolic ammonia into the pure EtBr, this side reaction can be minimized to increase yield, particularly during the first half of the addition.
1. But will this cause the formation of single and di-ethyl amines in preference? Can Ethylamine Hydrobromide react with EtBr to form Diethylamine HBr, and so on?
SWID was wondering about evolution of heat being a problem (since EtBr has a b.p. of ~38C).
A quick examination of the bond enthalpies shows the following:
(N-H * 3) broke @ 388 KJ/mol => -1164
(C-Br * 3) " " 276 " " => -828
(C-N * 3) formed @ 305 " " => +915
(H-Br * 3) " " 366 " " => +1098
----------------------------------------
Total: +21 KJ/mol
Inidicating that the reaction will be slightly endothermic. However, the formation of ammonium bromide from the ammonia and hydrogen bromide is not accounted for, and SWID feels there is something else missing from this equation as well. So, currently the methodology will not be designed with anything more than a cool water bath. (Monitored, of course.)
2. What, if anything, is SWID missing?
Ok, so here is SWIDs plan as of current:
A teflon stir-bar followed by 326.91g (3 mol) of Ethyl Bromide will be placed in a 1L RBF, and this set in a cool (5-10C) water bath on a magnetic stirrer. Next, an addition funnel containing 166ml of 0C ethanol saturated with ammonia (approx. 51.09g (3 mol) Ammonia) will be attatched, along with a thermometer dipping into the EtBr solution. The stirrer will be started at a reasonable rate, and the ethanolic ammonia will be dripped in at roughly 1 drop/second. After addition the flask will be removed from the bath and allowed to come to room temperature. If the solution is acidic, it will be basified with ammonia to ph~7-10, and the ethanol distilled off. The residue will be dissolved in dH2O at 10C, and then the temperature allowed to come to room temp. This is to utilize the property of TEA to be miscible in water below 18.7C, but only slightly soluble above 18.7C. The collected TEA will be washed with warm dH20 and warm brine, then dried over CaCl2 and distilled, collecting the fraction at 88-91C.
3. Repeat #2.
SWID very much sincerely would help the more knowledgeable bees looking this over and pointing out mistakes.
P.S. Posts are much clearer pre-written and then posted.
Drug Chemists are Ta to a good Sm.
(Chief Bee)
03-05-04 10:23
No 493110
I believe that the formation of tetraethylammonium bromide will be a bigger problem than any incomplete alkylation.
The Hive - Clandestine Chemists Without Borders
(Fragile ego)
03-05-04 11:10
No 493116
Post 330880 (foxy2: "Ethylamine and Triethylamine Synthesis", Chemistry Discourse)
http://www.democracynow.org/ - The Exception to the Rulers
(Hive Bee)
03-05-04 17:04
No 493173
Rhodium: Mmm, SWID was afraid of that. SWIDs methodology might work for creating some TBAB then. Will compare to whats already been posted for that purpose.
foxy2: Ah, SWID thanks you so much! He has no idea how he missed that in the TFSE. Looks like its time for him to get to work.
Drug Chemists are Ta to a good Sm.
(Hive Bee)
03-05-04 21:02
No 493212
Related, but regarding the TEAF b-nitrostyrene reduction posted on Rhodiums page (here: ../rhodium /cth.tea
First, are there any Bees who have "proven" this method using various favorite substrates?
Second, the article doesn't state how intrinsic the DMF solvent is to the reaction. Is the amide group in the solvent the important thing here, or is it the polarity, or what? (Obviously the solubility of the reagents matters.) Looking at the structures of TEAF and comparing to DMF, this does look to be the ideal solvent, but it just isn't available to SWID right now.
Third, would Ethylamine + Formic Acid => n-monoethylformamide? Can't find any refs for such a compound.
SWID is rambling. Help is greatly appreciated.
Oh wait, one last thing. Fourth, SWID is concerned about the reduction of the nitropropene derivative of asarone using this method, given asarones sensitivity to acid. Is this a valid concern?
Drug Chemists are Ta to a good Sm.
(Stranger)
03-05-04 22:45
No 493242
Third, would Ethylamine + Formic Acid => n-monoethylformamide? Can't find any refs for such a compound.
To my knowledge, carboxylic acids unfortunately don't form amides with amines... You'll have to make an acid chloride, or an ester from the acid first, and in this case the former is pretty much impossible I'm afraid.
"Formyl chloride has been shown to be stable in chloroform solution for 1 hr at -60 °C...[1]"
Read more in Advanced organic chemistry by Jerry March, 4th ed. p. 542.
Formation of formamides, same book, pages 640, 971, 979 and 1192.
[1]Stabb; Datta Angew. Chem. Int. Ed. Engl. 1964, 3, 132 [Angew. Chem. 1963, 75, 1203]
(Hive Addict)
03-05-04 23:22
No 493253
I seem to remember that it is possible to heat eg. methylamine formate to obtain N-methylformamide.
(Probably the reason why methylamine formate can be used instead of N-methylformamide in Leukart-Wallach reductive aminations).
HCOOH.NH2CH3 __Heat__> HCONHCH3 + H2O
So I guess the same is possible for N-ethylformamide.
http://www.movieconnection.it/schede/nos
(Hive Bee)
03-10-04 19:50
No 494237
(Rated as: good read)
Although this is a very basic reaction between a haloacid and an alcohol, SWID thought he would post his notes here for the future reference of anyone interested. Also, its good practice for when he has something useful to relay.
SWID started with the methodology of Alfred E. Holt as outlined here ../rhodium /tcboe/c
1st Run:
400mL 74% H2SO4 (4.69mol), followed by 263mL 95% EtOH (4.29mol) were added to the flask placed in an ice bath on a stirring hotplate, with the stir bar added before any of the reagents. After the solution in the flask had cooled to 5-10C, the stirrer was started and 164.6g of NaBr (1.59mol) were poured slowly into solution, allowing for not letting the stir bar stop. The distillation setup was attatched with ice cold water in the condenser and a 500mL recieving flask also in an ice bath. At this point it is worth noting that there was quite a bit of salts in the reaction flask, and SWID was unsure if this was undissolved sodium bromide or precipitated sodium sulfate. (More on that on second run.) The water bath was brought to 50C, and the contents of the reaction flask allowed to come to thermal equilibrium. Although some small amount of effervescence was observed in the flask, no distillate was coming over. The water bath was brought up to 75C, at which point the distillate began to come over. The temp was allowed to drop to 65C in an effort to find the "lowest temperature that the ethyl bromide will distill", but this was too slow. It was found that a 73C water bath (deep enough to cover the flask up to the 450mL point, with ~700mL of fluid in flask) produced a distillate at a rate of one drop every two seconds. The temperature of the distillate was, interestingly enough, 50-52C. This process was allowed to continue for about eight hours (2-3 hours my ass!), at which point the reaction was stopped, and SWID measured 62mL of crude EtBr in the recieving flask. He sighed, cleaned up the mess, threw stoppers on both the reaction and recieving flasks, threw them in turn into the fridge, and went to get some sleep.
The next day, the reaction flask had a thick crsytal cake in it, and pouring off the supernatent liquid revealed a rather beautiful crystal formation, like a porcupine with 2-3cm long crystal spikes. The cake, after admiration and hesitancy, was dissolved in a large amount of water and disposed of. SWID set down and did the math regarding the molar equivivalents, and realizing the ridiculous limitation of only ~1.6mol of NaBr, decided that was the reason for the low yield. Thus, he began run 2.
2nd Run:
Same setup, 400mL of H2SO4 + 263ml EtOH, chilled to 5-10C. This time however, SWID unthinkly dumped the entire portion of 329.3g NaBr (3.2mol), freezing the stirbar in the cake formed at the bottom. The water bath was brought to 75C for six hours, during which another measly ~50mL distilled over, at 50-52C. SWID let the setup cool, then added another 50mL of ethanol which resulted in spontaneous crystallization in the upper layer of the liquid portion of the flask. On swirling, it redissolved. The water bath was then raised to 90C, at which point the distillate came over at a much more respectable rate (roughly 1.5 drops a second), and still maintained the 50C. SWID noted that the bubbles in the reaction flask were not just being formed on the salt cake, but actually were forming as the cake was dissolving, which has led SWID to believe that to some extent the NaBr is coated by a passifying layer (at lower temps) of precipitated sodium sulfate. Another six hours and the crystallized salt on the bottom had disappeared. (Note that once the stirbar was finally freed, the distillation went MUCH faster.) Soon after the distillate temp began to climb while the volume decreased, and so the water bath was allowed to cool to room temp. The reciever flask had 300mL of crude EtBr in it at this point. (Note that the same reciever was used for both runs, with the run from 1 still in it.)
Purification:
Took the ~300mL distillate, washed 2x50mL dH20, 1x50mL of brine, and once more 50mL of dH20. Placed in a clean 1L flask with a "handful" of calcium chloride and a stirbar, and vigorous stirring was started. After roughly thirty minutes, the water bath (same one from before) was heated to 40C, and the EtBr began to distill at a very rapid rate (almost pouring out of condenser, but a ballon on the sidearm of the recieving flask indicated that it was all being condensed). The temp of the distillate was exactly 38C. After distillation was finished, SWID had 290mL of clean EtBr in reciever. SWID thinks it probably isn't 100% dry though, as after distillation it was distinctly cloudy.
Notes of changes from referenced methodology:
1. Unless, like Alfred E. Holt, Sodium Bromide is a difficult or expensive reagent to obtain, do not use such an excess of sulfuric and ethanol. It is just a waste. In fact, SWID would recommend scaling down some the molar ratios even if NaBr is harder to get.
2. SWID got the impression from the paper that a lower temp. water bath was needed. Not so. Just heat that sucker up to 90C, and do your purification in subsequent steps if your concerned. (SWID doesn't think diethyl ether is a serious byproduct of this reaction, even at 90C, considering that anything below 130C in the optimized synth of ether results in very low yields.)
3. Two hours is a joke, even with a 90C water bath. With vigorous stirring, maybe four or five.
4. The reaction isn't done until the cake in the lower portion of the flask is solvated.
5. Definetly pour in the NaBr slowly or in aliquats, with good stirring. Don't let the stir bar freeze up.
And there you have it.
Drug Chemists are Ta to a good Sm.
03-12-04 03:22
(Rated as: misinforming)
(Hive Bee)
03-12-04 05:48
No 494557
SWID thinks he is probably missing the obvious here, but no matter how many times he reads it, the following part of the Triethylamine synth linked above by foxy2 makes absolutly no sense.
"The alkaline distillate was collected under dilute hydrochloric acid (1 in 3). This hydrochloric acid solution was evaporated on the water bath till there was no odor of the acid and the product, when removed from the water bath, solidified to a crystalline mass after a few minutes. If this solid mass be again placed on the water bath, it melts partially and remains as a mixture of fine, white crystals of ammonium chloride and a transparent liquid, which was expected to be a mixture of hydrochlorides of ethylamines."
Ok, so how exactly are they melting TEA*HCl, which has a m.p. of 253C (Merck, 12th) on a water bath?? If it was the freebase it would make sense. SWID just has a gut feeling that the workup they propose isn't very good. He has a few as of yet undeveloped ideas, including distilling the TEA freebase from under an equal layer of dH20 to absorb some of the ammonia. See, undeveloped. Seperating two things so chemically similiar could be tricky. SWID is assuming that ammonia gas is VERY soluble in TEA freebase. (EDIT: SWID just realized that this step is where they are producing ethylamine, not triethyl. Nevertheless, EA*HCl has a melting point of 110C. Still makes no sense.
)Also, on an unrelated note, SWID was looking at ../rhodium /mdp2p.p
SWID was under the impression that MDP2P was a distinctly antifreeze yellow-green color. He has heard this phrase many times. Does it have to do with chiralty?
SWID thanks in advance for all the helpful help, and also wants to give me, Daphuk_up, a big pat on the back for my first good kharma.
Too bad SWID is completely fictional, like all events described herein.
Drug Chemists are Ta to a good Sm.
(Hive Bee)
03-12-04 10:09
No 494579
doesn't take much water or contaminant to depress the mp. or change the color of pretty much everything. note "crude". this reddish color is a common result. purification lightens it up, but i doubt it changes the symmetry as it does. Mr. Rakshit's article is excellent and you should have no problems if you follow it. let us know how you do.