(Hive Bee)
07-17-02 02:14
No 333551
(Rated as: excellent)
To a 500ml rb three-neck flask with a thermometer and a stir bar was added 16,6g (100 mmol) 2,5-dimethoxybenzaldehyde and 18,3g (150mmol) methyl 2-chloropropionate. 100ml MeOH was added to get the benzaldehyde into solution. While keeping the reaction mixture at 15 deg C, 8,1g (150 mmol) sodium methoxide in 50ml MeOH was added dropwise during 40min. When all alkoxide was added the reaction mixture was allowed to come to room temp and stir for another hour. The reaction mixture was then added to 10g (250 mmol) NaOH in 40ml water while keeping the temp at 20 deg C, then all was stirred at room temp over night. The next morning there was a thick white precipitate in the solution. To this 15% aq HCl was added until pH 3,5 was reached. This caused a clear yellow oil to fall out. The solution was heated on a waterbath at 65 deg C for two hours to complete the decarboxylation. The methanol was removed by distillation in a rotovap and the ketone was isolated by steam distillation. The distillate was extracted with 3x75ml toluene and the collected toluene phases dried over MgSO4. The toluene was removed by distillation in a rotovap leaving a clear yellow oil.
Yield: 14.94g (76,9 mmol) 2,5-dimethoxyphenylacetone
Purity: 96% by HPLC
Now where did I put the hydroxylamine and iodine?.....
(Chief Bee)
07-17-02 07:54
No 333599
Great Barium! I put this synthesis at ../rhodium /25dmp2p
But what are you going to do with the iodine?
(Hive Bee)
07-17-02 08:12
No 333603
Guess I´ll be needing some silver sulphate also.
I´m also right now trying another way of generating that carbanion. It does so far look very good. If this works one can forget about alkoxides and use 50% aq. NaOH instead.
More news tomorrow.
(Distinctive Doe)
07-17-02 08:13
No 333605
But what are you going to do with the iodine?
DOI, I presume.
Those who give up essential liberties for temporary safety deserve neither liberty nor safety
(Hive Bee)
07-17-02 08:41
No 333615
This can and will be improved, but it was just a first trial.
Aq. NaOH/Aliquat 336 instead of NaOCH3
16,6g (100 mmol) 2,5-dimethoxybenzaldehyde was added to 50ml toluene and 2g (approx 5 mol%)Aliquat 336 in a 250ml rb flask with a thermometer and a stirbar, then 5,6g (140 mmol) NaOH was dissolved in 7ml water and added to the flask. To this two-phase system 14,7g (120 mmol) methyl 2-chloropropionate was added dropwise during 30 minutes. The temperature was maintained at 20 deg C using a icebath. When the addition was complete the reaction mixture was stirred for another 30 minutes at roomtemp. 10g (250 mmol) NaOH dissolved in 50ml water was then added and the mixture was stirred for another hour at room temp. The phases was then separated and the aqueous layer saved. The toluene layer was extracted with another 50ml water and then discarged. The combined aqueous phaes was then acidified with dilute HCl until pH 3 was reached.
The lovely yellow oil comes once again....
I do not have time to work it up properly today but I will do that first thing tomorrow.
(Chief Bee)
07-17-02 08:55
No 333623
Wow, if this is tested on several benzaldehydes, it could become one of the preferred methods of synthesizing P2P's. It is a wonderful way around the use of nitroethane (which incidently also can be made from 2-halopropionic acid).
(Official Hive Translator)
07-17-02 09:17
No 333631
Barium, you did this!
Ah, how amazing!
Congratulations, congratulations!!
Yours,
Antoncho
(Newbee)
07-17-02 12:07
No 333713
Congrats Barium with your discovery
. SWIM has some questions though, mainly because he doesn't see the mechanism behind the reaction. When he tries to "solve" the problem, he finds a reaction like this:
Note that the charges symbolize partially charged atoms (SWIM didn't find the delta+/- in his editor
). He thinks that the chloropropionate reacts with the aldehyde by splitting HCl. As you see, he ends up with the C=O as 1-propanone, and not 2-propanone. On Rhodium's site, there is a pic with the formation of an epoxide, but SWIM fails to understand that epoxide formation reaction... 
.If this works as you advertised, then SWIM certainly wants to test this thing on other benzaldehyde derivatives. But maybe the ortho positioned MeO- is very important (to increase the partially positive charge on the alfa carbon relative to the phenyl), and you will need proper substituents on the phenyl to get equally high yields.
Just SWIM's thought... he could be very wrong
.-[ A Friend With W33D Is A Friend Indeed ]-
(Chief Bee)
07-17-02 17:24
No 333858
The base grabs the halogen from the alpha-halo ester, forming a carbanion, which adds to the carbonyl, forming the epoxide. The reaction is a Darzen Condensation, and you should be able to look up the detailed mechanism either online or at the library.
The epoxy ester is then hydrolyzed and the formed acid decarboxylated. During the decarboxylation, the epoxide also rearranges to the ketone.
(Hive Bee)
07-18-02 03:39
No 334060
The yield from the trial yesterday was 5,4g ketone. Not too shabby considering the very short reaction time and overall impatience. I just wanted to see if this twist actually could give something useful. I will now try to perform this reraction properly and see what I get.
By the way I´m currently running a batch of 2,4-dimethoxybenzaldehyde. This time I used NaOH dissolved in MeOH with aliquat 336. Just want too see if it behaves diffrent.
I´ll keep you informed
Soo many things to do, so little time....
(Hive Bee)
07-18-02 07:09
No 334113
Not optimized but pretty good.
100mmol 2,4-dimethoxybenzaldehyde, 120mmol NaOH, 2g aliquat 336, 50ml MeOH and 50ml toluene was stirred together in a 500ml rb flask. 120mmol methyl 2-chloropropionate was added dropwise over 20 min while the temp was kept at 20 deg C. When addition was complete stirring was maintained for another 30 min. 150mmol NaOH in 15ml water was then added and stirring was continued for 30 min.
Workup was done as before but without steam distillation leaving 6,7g 2,4-dimethoxyphenylacetone as a bright yellow oil.
Reaction times should be longer to give optimum yields.
But the method works!!
(Hive Bee)
07-19-02 08:48
No 334617
A 500mmol batch of 2,5-dimethoxybenzaldehyde was started yesterday. Procedure was exactly like the first one in this thread. Anhydrous conditions with sodium methoxide as the base.
Yield: 91,5g (94,2%) 2,5-dimethoxyphenylacetone as a yellow oil which becomes slightly orange over a couple of hours in contact with air.
This morning I decided to try a few different benzaldehydes just to see if they would give the corresponding phenylacetones as well. The reactions were not allowed to run full time.
100mmol 2-fluorobenzaldehyde 34% ketone
100mmol 4-fluorobenzaldehyde 38% ketone
100mmol 2,4-dimethoxybenzaldehyde 31% ketone
100mmol 3,4-ethylenedioxybenzaldehyde 42% ketone
Reaction conditions used were:
100mmol aldehyde, 2g aliquat 336, 120mmol NaOH as a 50% aq. soln. and 50ml toluene was stirred at 20 deg C. 105mmol methyl 2-chloropropionate added dropwise during 30 min while temp was kept at 20 deg C. Stirring was continued for 30 min then 150mmol NaOH in 50ml water was added and stirring continued for 1 hour. Phases separated and toulene phase extracted once with 50 ml water. The combined aqueous extracts was acidified to pH 3,5 with diluted HCl, heated to 45 deg C for 20 min, then extracted with 2x 30ml DCM. The combined DCM extractions was dried over MgSO4 and the solvent removed in a rotovap, leaving the ketone as a yellow oil.
I guess we have a winner.....
(Hive Bee)
07-19-02 16:09
No 334803
Hey Barium, the last P2P you mention is "3,4-ETHYLENEdioxy" compound. did you mean METHYLENEDIOXY? in either case, maybe this is a novel compound that could be explored with no more difficulty than regular MDMA compounds.
(Chief Bee)
07-19-02 17:57
No 334849
3,4-Ethylenedioxyamphetamine has already been evaluated in Pihkal and found to be inactive.
(Hive Bee)
07-19-02 18:19
No 334857
Completely inactive? that surprising- to aurelius anyway. thanks Rhodium. and Barium, aurelius thinks you meant methylenedioxy?
(Chief Bee)
07-19-02 18:27
No 334861
3,4-Ethylenedioxy-N-Methyl-Amphetamine:
DOSAGE: 200mg or more
DURATION: 3 - 5 h.
QUALITATIVE COMMENTS:
(with 150 mg) A flood of paresthesia at the 30 minute point, and then nothing. There was the development of a plus one-and-a half effect over the next hour with the tendency to drift into a dozing state with hypnogogic imagery. There were colored letters in the periphery of my visual field. There was no appetite loss nor was there any blood pressure rise. And no eye jiggle or teeth clenching. I was out of the experience in 4 to 5 hours. A repeat of this level a few days later gave a bare possible threshold with no other effects.
(with 200 mg) There was something unmistakable at 45 minutes, with hints of nystagmus. Possibly MDMA-like, with no indicators of anything psychedelic. Subtle return to baseline, and there were no after-effects.
(with 250 mg) Alert at 40 minutes, and to a clear ++ at an hour. Slight something in the eye muscles. Dropping thirty minutes later, and baseline at three hours.
(with 250 mg) I am at a bare threshold at best.
(Hive Bee)
07-21-02 01:33
No 335422
Aurelius: I really mean 3,4-ethylenedioxybenzaldehyde. I do not touch anything controlled without proper licences.
(Bee without a Title)
07-21-02 09:28
No 335492
nice peice of work Barium, hats off
(Stranger)
07-23-02 15:01
No 336249
Very cool.
With regards to the trials you ran using NaOH/aliquat 336, I would suspect that the lower yields you are seeing are due to the hydroxide saponifying some of the methyl ester on either the starting alpha-halo ester or the epoxy ester, such that there is not enough of the carbanion(due to either a lack of methyl 2-chloropropionate or NaOH) around to react with all of the aldehyde.
Did you check the toluene extracts for starting material?
You may be able to get the higher yields you are seeing with the NaOMe conditions by simply raising the amount of methyl 2-chloropropionate and/or NaOH in the first step until all of the aldehyde gets consumed.
Also, given the result you had with the NaOH/Aliquat 336 in MeOH/toluene, the PTC may not be neccesary. Just add the methyl 2-chloropropionate to the aldehyde/NaOH in MeOH.
Of course, I have no way of knowing whether you have already checked to see that the aldehyde is being completely consumed and the lower yields are due to some other reason.
Anyways, excellent work!
(Hive Bee)
07-24-02 05:36
No 336530
To verify the identidy of the 2,5-dimethoxyphenylacetone I decided to N-alkylate it with methylamine.
2,5-dimethoxyphenylacetone 30mmol
methylamine 40mmol
sodium borohydride 50mmol
Methylamine as a 25% aqueous solution was allowed to react with the ketone dissolved in 25ml toluene for 1 hour under violent stirring at room temp. The layers were separated and the toluene layer washed once with 25ml water. The toluene phase was added in one portion to a stabilised aqueous solution of sodium borohydride (the borohydride dissolved in 15ml water containing two drops of 50% aq. NaOH) and the mixture stirred violently for 1.5 hours at room temp. 20% aq HCl added dropwise until pH 2 was reached and the phases separated, the organic phase extractd twice more with 25ml water. The combined aqueous extractions were baified until pH 13 was reached and extracted with 2x30ml toluene. Drying, solvent removal and crystallisation yielded 4.1g (55%) 2,5-dimethoxy-N-methylamphetamine hydrochloride (2,5-DMMA) as bright white crystals. Crystallisation was performed in EtOAc which is a great solvent for this purpose.
(Hive Bee)
07-24-02 07:04
No 336556
Hi Beaker
It could very well be the reason for the lower yields. But I suspect that the very short reaction time is the primary cause. I intentionally shortened the reaction time just because I did not have the time to let it run full time. And the test verified that ketone could be made this way as well.
No did not check the toluene for substrate.
I will dig myself down in this reaction when a little more time is avalible. Imaging to be able to run this reaction in just MeOH without PTC....
(Hive Bee)
07-31-02 03:58
No 339354
(Rated as: excellent)
To a three-necked 3000ml rb flask with a stir bar add 166g (1mol) 2,5-dimethoxybenzaldehyde, 15g Aliquat 336, 159g (1.3mol, 139.5ml) methyl 2-chloropropionate, 500ml toluene and 200ml MeOH .With a cold water bath the temperature is brought down to 10-15 deg C. 60g solid NaOH is added in portions of 2-4g over two hours while not allowing the temperature to rise over 15 deg C.
Do not get to brave while adding the hydroxide because the temperature can rise very quick, and you do not want to mop up the haloester from the floor and ceiling – trust me.
When about about 30g NaOH has been added the solution becomes very thick from some precipitate but this will gradually dissolve again. If it becomes too thick to be properly stirred add some more MeOH.
When all NaOH has been added allow the solution to stir for another two hours at room temp.
Then add a pre-made solution of 100g NaOH in 450ml MeOH dropwise during 2 hours while keeping the temperature at 20-30 deg C. Keep it stirring at room temp for another 4 hours and the let it stand over night. The next day the solution will be very thick from precipitated crystals. Add 500ml water and the crystals will dissolve. Separate the two layers and extract the organic layer with another 500ml water. The toluene layer can now be discarged.
To the combined aqueous extracts conc HCl is added until pH 2.5-3 is reached. This will cause a yellow oil to fall out. Allow the acid solution to stir for one hour at room temp, add solid NaCl (enough to saturate the solution) and 500ml toluene and stir for 10 minutes.
Separate the layers and extract the aqueous phase once more with 250ml toluene. Wash the combined toluene phases once with saturated NaHCO3 solution, dry with MgSO4 and remove the toluene by distillation. This leaves 2,5-dimethoxyphenylacetone as a yellow oil.
Yield: 152g (0.78mol) 2,5-dimethoxyphenylacetone
(Chief Bee)
07-31-02 11:17
No 339448
Great - but what about distillation of the ketone? What is the isolated yield after that, and what is the boiling point of 2,5-dimethoxyphenyl-2-propanone?
(Hive Bee)
08-01-02 02:59
No 339755
I´ve taken my old friend the oilpump to the graveyard. All I have left is the teflon membrane pump used for my rotovap system. This pump is not good enough to perform vac distillations of ketones in my opinion. In a short while I´ll get a new oil pump then you´ll get more data.
(PVC-Analog Taste-Tester)
08-02-02 23:26
No 340488
Anyone know any patent #'s or synths for the methyl 2-chloropropionate?
Love my country, fear my government.
(Chief Bee)
08-02-02 23:55
No 340498
UTFSE for chloropropionate/bromopropionate/halopro
(Hive Bee)
08-13-02 14:03
No 345131
I was happy just to be able to locate 2,5,dmb.
Now, Barium, your telling me nothing has to blow up and I won't have to change indentities 5 times (radioactive precursors)?
Barium if you ever need rare blood or use of a kidney...
Dude, my life just got WAY more interesting...
Thank you and thank you hive!
The sky was the color of television tuned to a dead channel.
(Hive Bee)
08-13-02 23:07
No 345255
I found some semi-interesting patents by George Darzens for the reaction named after him. It is not exactly the same as what has been documented by Barium, i.e. synthesis of phenylaceton derivatives from benzaldehydes, but it could be useful for bees who like to experiment with amphetamine analogues. See for yourself
:- Patent DE174279 - Verfahren zur Darstellung von disubstituierten glycidsaeuren der allgemeinen Formel [...]
- Patent DE174239 - Verfahren zur Darstellung von Aldehyden der allgemeinen formel [...]
Doped(TM) since 19.... euhm... a long time
(Stunning)
11-12-02 23:21
No 379201
Barium or somebee else I've just to ask.
Have you ever tryed this rxn with non-substituted benzaldehyde? Does it works? If yes, how about rate of yield? Or maybe it has some other conditions?
Pliz, if it's not so complicated for you, confide with this magic with me
I'll be very grateful
!Wanna make laugh the GOD? - Tell him about your plans.
(Hive Bee)
11-14-02 08:20
No 379632
(Rated as: excellent)
I´ve made quite a few phenylacetones with this method now, and finally I´ve got a nice overall method.
1 mol of your favourite benzaldehyde
1.1 mol methyl or ethyl 2-chloropropionate
1.5 mol sodium methoxide, preferebly as the commercially avalible and dirt cheap 30% soln in MeOH.
Toluene, about 200-250 ml/mol benzaldehyde. Make sure the toluene is dry.
Add the toluene, benzaldehyde and haloester to a rb flask equipped with a mag stirbar, thermometer and a addition funnel. With cooling, add the sodium methoxide solution dropwise at a rate which keeps the reaction temperature between 10 to 15°C. When the addition is over allow the mixture to stir at room temp for one hour.
The toluene solution of the glycidic ester is now poured into 1 mol NaOH, as a 5% aqueous solution, and the mixture heated to 70-75°C for 60 minutes to hydrolyze the glycidic ester. The toluene layer is then separated from the aqueous layer. The sodium salt of the glycidic acid can now be isolated by concentration of the aqueous solution to about one third of the original volume and cooling to 10°C, filtration and washing with cold MeOH affords the salt in a quite pure form.
The phenylacetone is generated by heating the previous alkaline solution of the sodium salt of the glycidic acid to 90°C, and acidifying to pH 5.5 with either acetic acid or hydrochloric acid. A vigourous evolution of carbon dioxide starts immediately upon addition of acid. The slightly acidic solution is kept at 90°C for approximately one hour, or about 10 minutes after the carbon dioxide evolution has ceased. The solution is then cooled to room temperature, the pH raised to 8, and the ketone extracted with ether, DCM or toluene.
Catalytic hydrogenation freak
(Stunning)
11-14-02 08:40
No 379634
Double wow!
Many thanx, Barium.
Henry condensation is sux!
I'm your great fan
Make Drugs, not War!
(Hive Bee)
11-15-02 04:01
No 379941
Barium, what is the P2P yield?
(Hive Bee)
11-15-02 04:36
No 379946
I won´t be able to try it until my license drops in
Catalytic hydrogenation freak
(HyperLab Bee)
11-16-02 09:29
No 380249
Possible to replace methyl 2-chloropropionate
for Methyl (Ethyl,Butyl,) Chloroacetate in metod with phenylacetone ?
(Chief Bee)
11-16-02 13:35
No 380301
If you do that, the product will instead be the phenylacetaldehyde, which depending on structure might polymerize (or not).
See Patent US5057624 for a method.
(Master Whacker)
11-18-02 19:35
No 381024
Everyone!!!
Please examine the patent quoted by Rhodium above: Patent US5057624
That patent contains some amazing, possibly revolutionary information! Phenylacetaldehydes are aminated with AQUEOUS (30 & 40% soln) methylamine and aq. solutions of NaBH4. Amazingly enough, that patent may hold the key to the Hives next revolutionary technique- A LaBTop style borohydride MDMA synth from simple, easy to make methylamine solution rather than the scrupulously anhydrous conditions called for by the Masters(LaBTop) original technique!!! Although it isn't that difficult to run the procedure as described by LaBTop, it would tremendously simplify things if the NaBH4 could be added dropwise as an aq. soln rather than slowly adding the powdered solid reagent. Comments?
(Hive Bee)
12-09-02 06:19
No 387793
It has already been done
Post 328680 (Barium: "A really wet reductive alkylation", Novel Discourse)Catalytic hydrogenation freak
(Hive Bee)
12-09-02 06:29
No 387794
what the result would be if sodium methoxide is substituted for a strongly alkaline ion exchange resin? Dry sodium hydroxide gives decent results, 50% aq. sodium hydroxide/PTC gives so so results. The less then great yields with sodium hydroxide is most likely due to the fact that the hydroxide saponifies some of the halo ester before it has a chance to form a carbanion. Could this be prevented with the use of a dry alkaline ion exchange resin?
If so, the resin is regenerated very easily with 5-10% aq NaOH, washing with water until neutral and drying.
Comments..
Catalytic hydrogenation freak
(Hive Bee)
12-10-02 11:52
No 388164
Perhaps I am wrong, but I am very sure most of these reactions can easily be done by a biotransformation utilizing a system of active fermenting saccharomyces cervesiae or candida utilis with a carbon source, essential salts and coenzymes in water. The addition of acetaldehyde as hydrogen acceptor gives relevant higher yields. Yields >70% on benzaldehyde can be stated in a system transforming unsubstituted benzaldehyde to hydroxyphenylacetone. The reaction time is between 8 and 10 hours, the reaction itself is carried out in a usual fermenter whereby aeration seems to be a main factor. Literature also states that the oxygen masstransfer limits the reaction. Procedures for substituted benzaldehydes are to find in several patents and articles, this is a old hat to say it in short terms. The furtheron processing of the hydroxyphenylacetones is described in many variations including AL/Hg, Nickel catalyst, noble metal catalyst, with aqueous methylamine, with methylamine.HCL.... I can´t remember a variation not described.
So this yields hydroxyphenylacetones a dehydroxylation will be necessary for many wanted compounds. There can be no doubt that masterhydrogenators will solve this problem in one pot, as rumors go that complete dilletants have done this already.
but this is sure not feasible anyhow and wellknown to those skilled in the art.
I will troll back to crystal....
ORGY
(Hive Bee)
12-11-02 10:10
No 388449
How benzaldehyde is transformed to hydroxyphenylacetone:
To a 4 liter mixture containing sterile tap water, 400 gram molasses and 2000 ml brewers wort at 32°C in a usual fermenter 250 gram wet bakers yeast were given. Fermentation started. After one hour 3 gram MgSO4, 8 gram KH2PO4 and 20 gram (NH4)2PO4 were added and ph was adjusted at 4,7 by adding diluted H3PO4. This was allowed to cool down to 25°C. 35ml benzaldehyde in EtOH were added followed by 40 ml acetaldehyde in H2O. Two droppers were installed to drop in 40 ml benzaldehyde and 50 ml acetaldehyde during the next 4 hours. The fermentor was aerated and stirred during the whole procedure.
After 8 hours the yeast was filtered out and the water extracted with petrolether using a perforator. The extraction lasted 12 hours then the petrolether was boiled away and collected for reuse. The remaining sluggish brownish liquid substance, about 130 ml was vacuum distilled and the fraction coming over between 120° to 150°C @ 18 torr was collected. It was about 80 ml which were processed further by an Al/Hg reductive alkylation shameless copied from MaDMAx. Thanks Max! The result of 25 gram ephedrine is mostly to blame on slappy handling, low experience, not éxtracting the yeast and 47.123 more small mistakes adding up. But for it was l-ephedrine, (TLC comparism to a probably clean sample, melting point, taste...) the reaction before has to have produced hydroxyphenylacetone and that was what was to proove. It was the first run, a "proove of principle" and for this it was more than a success.
Important is heavy aeration with sterile air and permanent ph control with adjusting at <5,3. Doing some test batches with yeast only is adviced. The whole procedure is certainly more related to brewing than to chemistry what is not negative IMHO. Later runs gave better results, literature claims >70% on benzaldehyde and I think that thats realistic, >50% should be reachable for everyone with some excercise.
This works on substituted benzaldehydes also as I believe also I don´t know if the dehydroxylation is a problem then. PPA is easily made and perhaps a more direct way to 4-MAR is possible? I don´t know.
ORGY
(Hive Addict)
12-11-02 11:02
No 388469
aurelius presumes from the end product that the OH is in the alpha position, correct? (nice procedure) the brewer's wort, what is that? can the reactants (bz. ald. and acetaldehyde) be added in one large portion with decent yeilds?
(Hive Bee)
12-11-02 11:34
No 388479
Orgy,
To clarify a minor point, Swim is under the assumption that the brewers wort in question is simply a liquid barley malt, most likely canned, to which no additional h2o is added, is that the case?
Aurelius,
Organikum knows best, but swim believes from reading on the subject, adding the benzaldehyde etc. in a lump may poison the yeast and retard (or worse) the reaction in progress.
Iä-R'lyeh! Cthulhu fhtagn! Iä Iä!
(Hive Bee)
12-11-02 17:38
No 388593
The patent Patent US3338796 shows the possibility of using the described procedure on substituted benzaldehydes. Also an alternative fermentation medium is disclosed and a easy way for finding the right strain of yeast.
The synthesis described by me before is the best yielding known (the yields I got first time don´t count). Only if extracted and purified enzymes are used higher yields are propagated - up to 99%.
The "brewers wort" is here the wort as prepared for brewing a lager beer up to the point where the hops would be added. No hops and more important no boiling. The temperature of the malt (and wort) must never exceed 78°C. Or your coenzymes are gone. And for providing these coenzymes on a natural and cheap way the wort is used. Concentration of the wort should be this that it contains about 18% fermentable saccharose. A look for beer brewing answers most technical questions on fermentation, aeration, saccharose concentration, sterilisation.......
The used molasses should be made from sugar beets and contain about 50% sugar.
ORGY
(Hive Bee)
12-12-02 05:40
No 388761
This process is very amenable to being run in a "Bioreactor" (which is what the big Drug Companies do) and having the whole process automated. These bioreactors are composed of Glass Fermentation vessels, 1 liter and up. There is a top mounted motor for stirring, heating/cooling coils, and plastic feed lines for Air/Oxygen, and pH Up/Down, etc. Most have internal Oxygen and pH Sensors running to a computer control unit. You enter the parameters you want your fermentation batch to run at (i.e. temperature, pH, O2 levels, time to add other materials, etc) and the computer monitors and tweaks the "run". You can automatically add additonal materials (like benzaldehydes) at whatever rate and time you desire from bottles connected to peristalic pumps in the bioreactor. Most colleges with "Biotechnology" courses have one or more of these bioreactors. Older models turn up at auctions sites too.
http://biotech.tec.nh.us/BT220/Section_1
http://biotech.tec.nh.us/VLab/BioFlo.htm
(Hive Bee)
12-12-02 07:53
No 388777
A internet connection for the bioreactor is a "must have" yes?
It´s like a brewery. Modern mass production high tech breweries vs. old style small ones. What beer tastes better?
Process control by sensors and computers or you have to look yourself thats the difference - a bucket with lid or if you want to go big a vessel for wine making are sufficient for the engaged amateur. Stirrer is a paint stirrer attached to the drill and aeration by an big aquarium pump or a small compressor (oilless one, no fridge compressor).
I advice everybody to do a lot of testruns without substrate, with only the yeast.
I am a tekkie myself but its not necessary and brings no better results. Sorry, this is 3rd world technology, this is ghetto. Whereby ghetto isn´t the right word - this is Missisippi?
ORG
(Hive Bee)
12-12-02 20:23
No 389004
Yup, one can dump everything in a H2O 5 gallon glass jug and get it to work, BUT.... used technology is "cheap" and can make for tighter, better tweaking of fermentation params.
Ghetto here, thanks to the Internet, can mean finding what was a $20K technology at one time, for pennies on the dollar.
You'd be surprised what shows up on ZBay and college "garage sales", and used equipment sites. That Pentium computer one can buy for $50 is more powerful than a mainframe 20 years ago.
Technology rules! The War Is Over!
(Hive Bee)
12-13-02 00:50
No 389042
Oh oh, this to me for I get beaten all time for being tekkie. <sniff>
No, of course it´s possible to get these parts quite cheap, but most would have to learn to operate them first...
A bucket is easier - no manual needed. If you go and invest some money, so do it for a glucometer, a oxymeter and a good ph control device which adds the phosphoric acid and holds the ph at a certain level.
The process has overall a very high tolerance wherein yields vary only slightly. You have to fuck it realy up before yields suffer badly. But for to be true: As long as I can buy toluene and EtOH by the tanker I don´t mind 10% up or 10% down. Byproduct is benzylalcohol which is easily converted to benzaldehyde again - nearly no loss, just a bigger bucket.
And a perforator for the extraction - who wants to boil 50 liters water away?
ORG
(Hive Bee)
12-15-02 15:14
No 389784
You have a point about the bucket being simpler, if you factor in either the knowhow needed to use the hybrid mechanical/electrical/pheumatic/electron
And a bucket would sure be simpler than the design and development work needed to build a homegrown automation system using modern sensors and process control compononents.
But consider one other option...
What if opensource software were available that could do the following with cheep and readily available components
Component: X10 dimmer (<$20)
Uses: * Adjust current to heater coils for temp control
* Adjust speed of DC stirrers,pumps and fans indirectly
thru a linear AC/DC supply (most wall warts)
Interface: Shareware ActiveX control & X10 rs232 interface $25
Component: Cuecat (nearly free) or broken optical mouse
Uses: rotation counters for spinner flow control
Interface: rs232 or USB
Component: Cheep Web Cam ($20)
Uses: Read a cheep automotive vacuume gage
watch sesitized paper for the presence of H2S or
other toxic substances
Interface: USB & thresholding/position mapping BMP's dropped
out of an activeX
Component: Sound card - A/D thru a single chip Vol to Freq convter
Uses: Ph, temp, O2, conductivity using cheep probes off the
internet
Component: R/C servo's - ($10)
Uses Attached to small valves for dripper control, flow control
purge or relief falves
No circuites would have to be built by the user, any one of ten garage type companies will whip out and sell about any circuite you can describe without
case or powersupply for under $20, no questions asked.
The key is some clever opensource software, with a set of core routines to provide some base functionality aod structure with some LCD compatable HTML UI. The interface and higher level logic could be simplified by the core providing a rule firing shell that executes VBScript rules. To further simplfy the most basic customization, the core would automatically store parameters and history for the rules scripts, allowing any parameter to be profiles or externally controled by non-coders.
The bottol line...
A user could download a recipee/script off of the internet and succeed with
reactoins that they didn't even begin to understand the details of. They would
just keep the feeder bottle from going dry, and the power on. And assembly of the components would not necessarily be more complicated than plugging together a component sterao, once the sofware had matured a little bit and found a few good neighbors in the 3rd party hardware crowd.
That would make a bucket, and all the understanding and skills necessary to determine reaction conditions and proper responses and adjustments seem quite complicated in comparison.
And on the eight day, God created Meth...
... and hasn't done much of anything usefull since!
(Hive Bee)
12-15-02 21:14
No 389889
The construction plans for a simple matter converter would solve most problems...
ORG
(Hive Bee)
12-17-02 07:12
No 390233
DEA would deam that an illegally usefull device, emergecy schedule it with a retroactive death penalty for the inventors. Confiscate them all and use them to produce bullshit in an ever increasing quantity.
TrickE
And on the eight day, God created Meth...
... and hasn't done much of anything usefull since!
(Chief Bee)
12-25-02 22:24
No 392894
Speaking of Darzen, the name reaction database below (the most comprehensive I have seen to date) links to my page under the heading "Recent Academic References" - nice to see that my page carries at least some weight to professional chemists around the world
http://people.bu.edu/jaylowe/Named%20rea
(Hive Addict)
12-26-02 10:00
No 393028
That's not the only Reaction your page shows up on as a reference. aurelius thinks that the author of that page might be a Bee
that was part of the reason that aurelius decides to post the link for it.
(Hive Addict)
03-26-03 05:40
No 421443
(Rated as: excellent)
Here some "historic background":
G Darzens. Condensation glycidique des aldehydes avec l'ether alfa-chloropropionique. C R Hebd Seances Acad Sci 142 (1906) 214-215.
Since we were able to set up a general method for the preparation of alfa,beta-substituted glycidic ethers by condensation of a ketone with alfa-chloropropionic ether 1, it was important for our work to evaluate if the same method would be applicable on aldehydes.
The condensation of chloroacetic acid homologues with aldehydes is much less general then the condensation with ketones. However, it is very remarkable that this reaction works while the same reaction with monochloroacetic ether fails miserably.
I was able to synthesize alfa,beta-disubstituted glycidic ethers by condensing acetaldehyde, propylic aldehyde and isovaleric aldehyde, but the yields were always very poor (never higher than 20-30%).
Saponification of these ethers yields rather stable acids; decomposition by heating was a most complex thing and I was unable to obtain ketones this way.
Trioxymethylene condenses swiftly and yields alfa-methylglycidic ether, also prepared by Melikoff.
However, in sharp contrast with these results is the high yield one can get with aromatic aldehydes. The obtained glycidic acids are easily decomposed, setting free a ketone of type R-CH2-CO-CH3.
- Benzaldehyde: gives a yield of 50% of the alfa-methyl-beta-phenylglycidic ether. Liquid boiling at 153-154° at 18 mmHg. The free acid is decomposed by vacuum distillation, setting free methylbenzylketone (characterization by its semicarbazone).
- Anisaldehyde: yields alfa-methyl-beta-anisylglycidic ether, boiling at 189-190° at 20 mmHg. Its Na salt decomposes by simply boiling its solution in Na2CO3. The resulting PMP2P is characterized by its semicarbazone and its oxime.
- Piperonal: gives a glycidic ether which biils at 205-210°C at 25 mmHg. MDP2P can be obtained in a similar way as PMP2P by boiling the Na salt.
- Furfurol: its aromatic aldehyde analogues are known, and I was able to prepare ethyl alfa-methyl-beta-furfurylglycidate
The original text is available at Gallica.
The faster you run, the quicker you die.
(Distinctive Doe)
03-31-03 14:49
No 422850
What do ya know, nobody used TFSE
Post 285765 (foxy2: "Piperonal to MDP2P", Novel Discourse)
That thread has a patent ref for Bariums Procedure, 2-Chloropropionic acid methyl ester synthesis ref and 2-Chloropropionic acid synthesis refs. It goes quite nicely with this thread.
(Newbee)
04-03-03 15:47
No 423690
Add the toluene, benzaldehyde and haloester to a rb flask equipped with a mag stirbar, thermometer and a addition funnel. With cooling, add the sodium methoxide solution dropwise at a rate which keeps the reaction temperature between 10 to 15°C. When the addition is over allow the mixture to stir at room temp for one hour.
The toluene solution of the glycidic ester is now poured into 1 mol NaOH, as a 5% aqueous solution, and the mixture heated to 70-75°C for 60 minutes to hydrolyze the glycidic ester. The toluene layer is then separated from the aqueous layer. The sodium salt of the glycidic acid can now be isolated by concentration of the aqueous solution to about one third of the original volume and cooling to 10°C, filtration and washing with cold MeOH affords the salt in a quite pure form.
Now does Barium mean that he hydrolyze the entire solution? Or does he seprate the toluene first then hydrolyze, only the toluene?
(Hive Addict)
04-04-03 01:23
No 423825
Barium does indeed mean that the toluene solution is combined with the NaOH solution and the two solutions are heated for one hour under constant stirring. The ester which was made in toluene is now hydrolyzed and becomes a sodium salt wich is not soluble in toluene anymore, but it is soluble in water. Thus, the crap stays in the toluene and the product moves to the water phase.
Freaky
(Newbee)
04-04-03 09:44
No 423890
sometimes, it takes a few readings to get things together, for some reason i was thinking that there was a aq layer along with the toluene, but i see the error of my ways. Thanks Barium
(Hive Addict)
10-05-03 13:00
No 462777
http://people.bu.edu/jaylowe/Named%20rea
mentions that the Darzen reaction can also be catalysed by an acid, does anyone know anything about that ?
Also, while I'm in asking-mode: would it make any difference, which PTC is used, i.e. could TBAB substitute for Aliquat 336 ?
--psyloxy--
(Hive Bee)
10-05-03 13:50
No 462781
A rather large scale synthesis of this precursor can bee found in Patent US4334083
(Chief Bee)
10-05-03 16:18
No 462801
(Rated as: excellent)
Patent US4334083, Example 1:
A round-bottomed flask is used which is equipped with a stirrer, a Vigreaux-type condenser, a thermometer, a dropping funnel and liquid nitrogen traps arranged downstream of the condenser.
Methyl lactate (832 g, 8 mols), [a]D20 = +7.48° (without a solvent), is placed in the dropping funnel and thionyl chloride (1060 g, 8.9 mols) and pyridine (4.15 g, i.e. 0.49% by weight of the amount of methyl lactate to be converted) are placed in the flask.
The methyl lactate contains about 1.03% of ethyl lactate as an impurity and 0.61% of other impurities including methyl lactyl-lactate.
The temperature of the flask is raised to 60°C, whilst stirring, and the methyl lactate is run in over a period of 4 hours, whilst keeping this temperature constant. When the introduction is complete, the temperature is raised to 75°C. and this temperature is maintained for 1 hour. Analysis by gas phase chromatography, carried out at this moment, shows that there is no more methyl lactate in the reaction mixture. Heating is continued for 20 minutes and the mixture is then left to cool for 20 minutes, under a partial vacuum of about 150 mmHg, to a temperature of about 40-45°C.
A crude product (992.5g 884 ml), comprising crude methyl 2-chloropropionate, SO2 (19.2 g), SOCl2 (1.6g) and HCl (1.8 g), is obtained.
Analysis, by gas phase chromatography, of the crude methyl 2-chloropropionate thus obtained gives the following composition by weight (excluding SO2, SOCl2, HCl and pyridine):
97.7% - Methyl 2-chloropropionate
1.22% - Ethyl chloropropionate
0.04% - Methyl acetyl-lactate
0.08% - Methyl acetyl-lactyl-lactate
0.67% - Chloropropionate of methyl lactate
0.01% - Chloropropionate of ethyl lactate
0.03% - Lactide (cyclised methyl lactate)
0.11% - Chloropropionate of methyl lactyl-lactate
0.14% - Unidentified impurities
The formation of ethyl chloropropionate, methyl acetyl-lactate and methyl acetyl-lactyl-lactate results from the impurities present in the starting methyl lactate (yield of methyl 2-chloropropionate: 98%).
The crude product obtained above (900 g) is distilled, under a pressure of 20 mmHg, in a 40 cm high packed column. When distillation is complete, the vacuum is increased to 3 mm Hg. At the outlet of the packed column, the uncondensed vapours pass into a liquid nitrogen trap.
Distillation makes it possible to obtain the following three fractions:
Methyl 2-chloropropionate (95 g) of optical rotation [a]D20 = -25.37° (without a solvent)
Methyl 2-chloropropionate (675 g) of optical rotation [a]D20 = -25.26° (without a solvent)
Methyl 2-chloropropionate (71 g) of optical rotation [a]D20 = -24.56° (without a solvent)
At the bottom of the column, a residue (13 g) consisting of heavy products is recovered. In the liquid nitrogen trap, methyl 2-chloropropionate (17 g) containing traces of HCl, SO2 and SOCl2 is recovered.
After distillation, and taking account of the 2-chloropropionate recovered in the nitrogen trap, the yield is 97.2%.
(Heavyweight Chempion(eer))
10-06-03 01:39
No 462924
I have searched but not found anything interesting on that topic yet. Someone with online access to the major chemical search engines could perhaps give it a try?
The only requirement of the PTC is a hydrophobic nature and the ability to carry hydroxide ions from the water pahse to the organic phase where they can rip off protons. So, a large nuber of PTC's can be used.
Worthy
(you can always take some more)
10-06-03 10:08
No 462989
The articles describing the acid catalysed Darzens condensation are according to "Advanced Organic Chemistry - fourth ed." :
Sipos; Schöbel; Baláspiri J. Chem. Soc. C 1970, 1154
and
Sipos; Schöbel; Sirokmán J. Chem. Soc., Perkin Trans. 2 1975, 805.
I don't have access to the two articles right now, but i'll post abstract + full PDF first thing in the morning!
Regards
Bandil
I just love the smell of bromine in the morning!
(you can always take some more)
10-07-03 02:17
No 463168
I'm sorry, but the library i have access to, is not carrying those articles. Anyone who's had more luck than I?
I just love the smell of bromine in the morning!
(Chief Bee)
10-07-03 05:27
No 463193
Yes, both articles by Sipos has been retrieved a long time ago by lugh. Search for "darzen" in Post 436354 (Rhodium: "Archive of "Wanted References" Volume 1", Novel Discourse).
(Chief Bee)
02-13-04 11:51
No 488412
(Rated as: excellent)
The Darzens Glycidic Ester Condensation
M.S. Newman & B.J. Magerlein
Organic Reactions, Vol 5, Ch. 10, pp. 413-440 (1949) (../rhodium/pdf /darzen.org.r
Contents
Introduction
Scope and Limitations
Carbonyl ComponentsHalogenated EstersOther Halogenated Compounds Side ReactionsSelection of Experimental Conditions
Conversion of Glycidic Esters into Aldehydes or Ketones
Reactions of Glycidic Esters
RearrangementReactions with Hydrogen HalidesReactions with Ammonia and Amines ReductionGrignard ReactionHydrationReaction with Active Methylene GroupsThe Dichloroacetate Synthesis
Experimental Procedures
Methyl 
-Methyl-,
-epoxycyclohexylideneacetateEthyl -Methyl--p-tolylglycidate Ethyl -Methyl--phenylglycidate HydratropaldehydeEthyl -p-ChlorophenylglycidateEthyl -Chloro--hydroxy--phenylbutyrateExamples of the Darzens Glycidic Ester Condensation
Tables
I. Glycidic EstersII. Glycidic AmidesIII. -Chloro -Hydroxy Esters
The Hive - Clandestine Chemists Without Borders
(Newbee)
02-13-04 13:09
No 488433
(Rated as: good read)
I feel the need to point out this modification of the Drazens condensation wich has recently been discussed: Post 487007 (Fomalhaut: "Ïðîäâèíóòûé Äàðçàí", Russian HyperLab)
Though this interesting paper has been on Rhodium's I feel it hasnt been highlited enough.
Synthesis of Glycidic esters in a two-phase solid-liquid system
S. Gladiali and F. Soccolini
Synth. Commun. (1982), 12, 355 (../rhodium/djvu /gladiali.dj
EXAMPLE OF EXPERIMENTAL
Preparation of 3,4-dimethoxyphenylacetone.
A suspension of anhydrous potassium carbonate (6.9 g, 50 mmoles) in DMF (7.8 ml, 100 mmoles) containing veratraldehyde (4.15 g, 25 mmoles), methyl alpha -chloropropionate (3.8 ml, 35 mmoles) and Aliquat 336 (0.5 g, 1.25 mmoles) was vigourously stirred under nitrogen at 40C for 46 hours. At this time the conversion, estimated by GLC (200C), was about 95%. The reaction mixture was processed as above and the ethereal solution containing the glycidic esters was stirred at room temperature with 50% aqueous NaOH (4 ml). A vigourous reaction took place immediatly and the sodium glycidate separated as a thick paste. The mixture was stirred for ten minutes and then water was added (50 ml). The aqueous solution was separated, acidified with HCl (pH= 1) and stirred at 40C until the evolution of carbon dioxide ceased(30'). The oily product which separated was taken up in ether (30 ml) and the ethereal phase was dessicated (Na2S04). Evaporation of the solvent gave crude 3,4-dimethoxyphenylacetone (3.87 g, 80% yield), more than 98% pure on GLC (180C): b.p. 138-140C(1Torr) (lit. 135C at 0.8 Torr) 16; NMR: 6.67 (m, 3H); 3.60 (s, 6H); 3.48 (s, 2H); 1.87 (s, 3H); M + m/e 194 (calcd. 194). When TEBA was employed as PTC catalyst for the Darzens condensation, the hydrolysis of the glycidic esters required more time to be complete (3 hours) and the overall yield was slightly reduced (72%).
" Unorthodox cooking, illicit cooking. A bit of real science, in fact. "
(Hive Bee)
02-23-04 06:11
No 490584
Quite old post, but still I'm wondering one thing about the workup..
The methanol was removed by distillation in a rotovap and the ketone was isolated by steam distillation. The distillate was extracted with 3x75ml toluene and the collected toluene phases dried over MgSO4. The toluene was removed by distillation in a rotovap leaving a clear yellow oil.
As my rotovap is still broke I'll just evaporate the methanol off to get the crude ketone, but is there any reason to steam distill the ketone? Would just simple wash be enough for purification?
det gjør ikke noe, dekk ting!
(Hive Addict)
06-21-04 14:57
No 514668
J.Chem.Soc. Perkin Trans.1;10.1995;1247-1250
ethyl (R)-2-chloropropanoate
To neat ethyl (S)-lactate (50g, 424 mmol) containing DMF (0.3 ml) was carefully added neat SOCl2 (33ml). The mixture was refluxed until the evolution of SO2 ceased (3h). The crude mixture was poured onto ice and was extracted three times with ether. The combined ether extracts were washed with brine and dried (MgSO4) and the ether was evaporated under reduced pressure at room temperature. The resulting yellow oil was distilled to provide the title compound (43,6g, 319mmol, 75%), colorless oil; bp 143-145°C.
--psyloxy--
(Hive Addict)
06-21-04 23:57
No 514668
(Rated as: good read)
J.Chem.Soc. Perkin Trans.1;10.1995;1247-1250
ethyl (R)-2-chloropropanoate
To neat ethyl (S)-lactate (50g, 424 mmol) containing DMF (0.3 ml) was carefully added neat SOCl2 (33ml). The mixture was refluxed until the evolution of SO2 ceased (3h). The crude mixture was poured onto ice and was extracted three times with ether. The combined ether extracts were washed with brine and dried (MgSO4) and the ether was evaporated under reduced pressure at room temperature. The resulting yellow oil was distilled to provide the title compound (43,6g, 319mmol, 75%), colorless oil; bp 143-145°C.
--psyloxy--
(Chief Bee)
09-04-04 13:47
No 529539
(Rated as: good read)
Efficient Synthesis of α,β-Epoxy Carbonyl Compounds in Acetonitrile:
Darzens Condensation of Aromatic Aldehydes with Ethyl Chloroacetate
Zong-Ting Wang, Li-Wen Xu, Chun-Gu Xia, Han-Qing Wang
Helvetica Chimica Acta, 87(8), 1958-1962 (2004) (../rhodium/pdf /darzen.ethyl
Abstract
The Darzens reaction of ethyl 2-chloroacetate (1) with aromatic aldehydes 2 in the presence of polymer-supported or nonsupported quaternary ammonium salts proceeds under mild conditions by phase-transfer catalysis to give the corresponding epoxides 3 in satisfactory yields (Tables 1 and 2). With both MeCN as solvent and polystyrene-supported catalysts, diastereoselective Darzens reactions proceed in excellent yields and short times, with a fair degree of stereoinduction.
The Hive - Clandestine Chemists Without Borders
(Chief Bee)
10-11-04 21:43
No 535388
(Rated as: good read)
Synthesis of 1-(2-Furyl)-2-alkanones
Eldon H. Sund and David Scott Hunter
J. Heterocyclic Chem. 11, 1123-1124 (1974) (../rhodium/pdf /darzen.aryla
In connection with our interest in enolizable ketones, it was found of interest to synthesize a series of 1-(2-furyl)-2-alkanones. Previously three of these ketones were prepared by Hass, et al.3 by the condensation of 2-furaldehyde and the requisite nitroalkane with subsequent reduction of the resulting nitroalkane to yield the ketone. This method lacks generality because of the difficulty in obtaining higher homologs of the nitroalkanes.
A convenient method of preparation of these ketones is the Darzens glycidic ester condensation and subsequent hydrolysis and decarboxylation of the glycidic ester to yield the requisite ketone. The ethyl 2-bromoesters were either purchased or prepared by the method of Schwenk and Papa4. These ethyl 2-bromoesters were condensed with 2-furaldehyde essentially as described by Ruzicka and Ehmann5. The resulting glycidic ester was not isolated, but rather saponified and decarboxylated in the usual manner to yield the 1-(2-furyl)-2-alkanone, usually in good yield.
Experimental
Preparation of 1-(2-Furyl)-2-alkanones
A mixture of 29.8 g (0.31 mole) 2-furaldehyde and 0.31 mole of the ethyl 2-bromoester were cooled to 5-10°C. While maintaining this temperature and with stirring a solution of sodium ethoxide prepared from 13.8 g. (0.60 mole) sodium in 150 mL of ethanol was slowly added to the aldehyde-ester mixture. The reaction mixture was stirred an additional 30 minutes at this temperature and then allowed to warm to room temperature with an additional 2 hours of stirring. Approximately 30 mL of water were added to the flask and the mixture stirred on a steam bath for 3 hours. The reaction mixture was cooled to room temperature and a sufficient quantity of dilute phosphoric acid was added to the solution to bring the pH in a range of 3-4. As the acid was added a large quantity of carbon dioxide was evolved. The ketone was extracted with ether, washed with 5% sodium bicarbonate solution, water and dried over anhydrous sodium sulfate. After removal of the ether by flash distillation the ketone was distilled through a Nester-Faust annular Teflon spinning-band column under reduced pressure. These ketones are shown in Table I.
References
[3] H. B. Hass, A. G. Susi and R. T. Heider, J. Org. Chem. 15, 8-14 (1950) (../rhodium/pdf /nitro.alkene
[4] E. Schwenk and D. Papa, J. Am. Chem. Soc. 70, 3626-3627 (1948) (../rhodium/pdf /alpha-bromin
[5] R. Ruzicka and T. Ehmann, Helv. Chim. Acta 15, 160 (1932)
The Hive - Clandestine Chemists Without Borders