A journey with Cheapskate's MQ Synthesis

jsumner · Thu Mar 24, 2005 7:14 pm

I am hoping someone here can help. AFOAF ordered o-Toluidine HCl as o-Toluidine was not available through the distributor. Well it was believed that this would just be a simple matter of mixing the o-Toluidine HCL with some water and NaOH to arrive at the o-Toluidine. But, this is not that easy and I am looking for solutions. AFOAF started with 100g of o-Toludine HCl. This powder, o-Toluidine is a liquid with a s.g. just over that of water and almost equal, was mixed with almost 2 liters of DH2O and thirty grams or so of NaOH. The NaOH was the correct stoichemetric amount to neutralize (?) the HCl and freebase the o-Toluidine. Now all the o-Toluidine HCl powder has yet to dissolve in the 2 L of DH2O. There is about half left from the vacuum filter cake. The solution was vacuum filtered and the filtrate has two layers. The upper layer appears to be the DH2O though it is discolored brown and the bottom layer appears to be an emulsion of some sort. The volume of the bottom layer is much greater than the ~100 mL of o-Toluidine expected. I would appreciate some help with where to go from here to save this material and recover the o-Toluidine. I am thinking that I may just want to try and distill the emulsion as when the powder was being mixed with the NaOH solution there was a small bit of heat applied and the warm filtrate did not have any emulsion.

Please Help.

Thanks,
JS

Dr.Bunsen · Thu Mar 24, 2005 8:16 pm

The toluidine can be extracted with diethyl ether. Distill the organic layer under reduced pressure.

jsumner · Thu Mar 24, 2005 9:36 pm

Just so I am clear. This person should mix the remaining filter cake with Diethyl Ether and the the o-Toluidine should be distilled from the ether. Or should the filtrate be extracted using diethyl ether and then distilled. Please bear with me as I am more experienced in commercial size processes.

Thank you in advance,
JS

Dr.Bunsen · Thu Mar 24, 2005 10:06 pm

You can wash the filter cake with ether and extract the filtrate (o-toluidine is soluble in water 15g/l). I think the toluidine*HCl is not soluble in ether, but you can try it.

jsumner · Fri Mar 25, 2005 1:41 am

I am still just a little bit confused so please bear with me. Every time I read this I think I understand but then I think that maybe we are not on the same page. My apologies but I want to ensure I know what is recommended.

I was told that my FOAF now has the following material:

1. A filter cake of o-Toluidine HCL that has been recovered from a very dilute aqueous solution of NaOH. The NaOH was used in an attempt to freebase the o-Toluidine from the salt. (I assume this cake is still the o-Toluidine as it is still powder form and not liquid)

2. Almost 2L of filtrate. This is liquid. This fitrate was recovered by vacuum filtering a mixture of o-Toluidine HCl, distilled H2O, and NaOH pellets in an amount to stoichemitrically react with the HCL present in the 100g of o-Toluidine HCl. There are two liquid layers in this flask. The top layer is a brownish tint. (maybe due to dissolved o-Toluidine) I assume this is the aqueous phase. The bottom layer appears to be an emulsion of some sort. (slightly milky in color, not a "flat line" separation between the phases it really kind of looks like the fat they collect when the show a liposuction procedure on TV)

A little backgroud on the filtrate:
1. These two separate layers did not exist from the first filtrate while it was still warm from trying to help the o-Toluidine HCl dissolve in the water and NaOH solution.
2. While the first filtrate was cooling, the filter cake, heck call it wet powder, was mixed again with only distilled H2O this time. Then this solution was vacuum filtered. Heat was applied again but to a much lesser extent as it only got to about 35C. As a result this filtrate was cooler. This was then added to the first filtrate.
3. The combine filtrates were initially cloudy and then proceeded to separate into these two layers.

I am assuming that the bottom layer is the o-Toluidine emulsified in H2O. Now my FOAF is reluctant to use diethyl ether and would prefer something less volatile and less odorous. It was thought that a straight distillation might work but there will be leftover NaCl and NaOH in the distilling flask with the o-Toluidine and this maybe detrimental to subsequent reactions so extraction seems necessary. Once the o-Toluidine is recovered from the filtrate I would say that it is just a matter of repeating the all this with the remaining filter cake until it is consumed.

Next time I was told that my FOAF is just going to order o-Toluidine from a different supplier and skip this big hassle. It was thought that this would be simple to do. Well live and learn. At least I hope no one else will try this now that they see how involved it is.

I would really appreciate feedback on my thoughts that I plan to pass on my my friend who will then pass them on to her friend.

Thank you,
JS

Dr.Bunsen · Fri Mar 25, 2005 2:44 am

It's very easy. Wink

Pour 20ml of filtrate #2 (10ml of the top layer and 10ml of the bottom layer) into a separation funnel. Add 10ml ether and shake it. You'll probably get a top layer with toluidine + ether and a bottom layer with H2O, NaOH, NaCl and toluidine*HCl. Take the top layer and distill it.

If this works you can do the same with the rest of filtrate #2.

This is interesting, too. http://www.orgsyn.org/orgsyn/prep.asp?prep=cv4p0047

jsumner · Fri Mar 25, 2005 3:40 am

Dr. Bunsen,

Thank you very much. I will pass the info along. Though I suspect that the person will try to use Toluene instead of Ether first. The BPs between o-Toluidine and Toluene are almost 100 C apart so this should allow a simple distillation. I will let everyone know the result when I hear. I also wanted to thank you for the link. This is pretty interesting and I will surely pass this along as well.

Regards,
JS

starl1ght · Fri Mar 25, 2005 2:27 pm

you should watch out messing about with o-toluidine, it is likely a human carcinogen. Working with it without knowing what you are doing could lead to you getting various types of cancers (bladder cancer in the main I think).

jsumner · Fri Mar 25, 2005 7:13 pm

I also understand that my FOAF tried the extraction with Toluene and that this seemed to clear up the brown water to where it was almost clear. They also said that the second lower liquid phase disappeared and that the Toluene took on a brownish orange tint. This color matches that of 2-chloro aniline. I was also told that this person begun a quick distillation, though stopped it without completing, and the distillate was water white. He also started to try and convert the remaining o-Toluidine HCl overnight and it was not finished. He stated that he plans to spend tonight obtaining the o-Toluidine and the weekend continuing on in the reaction steps. I will let everyone know how it turned out once I am informed. Though, lesson learned IMO, never get the salt if the reagent you need is the freebase. In other words, try to keep the number of steps to an absolute minimum.

JS

jsumner · Mon Mar 28, 2005 10:29 pm

Well I have heard how this went. This conversion of o-Toluidine HCl to o-Toluidine turned out to be a waste of time. From what I understand the yield of o-Toluidine was terrible. Around 10%. A good amount of the salt remained a salt even after prolonged boiling in a dilute caustic solution. As my friend's friend was not comfortable using ether for the extraction of the o-Toluidine he used Toluene. This was then distilled off. The remaining material was not solely liquid and may have been a result of excessive heat. This material was crystalline in nature and some of it was liquid. I would therefore say that using a salt as a starting point would not be recommended though if someone here has had sucess with this I would like to know but I doubt that this person will ever try this again. I hope that this information is useful to my fellow enbthusiasts here and that it saves someone else the expense and aggravation of trying this same experiment.

jsumner · Wed Mar 30, 2005 2:37 am

So now I understand that my friend's friend was able to order some pure o-Toluidine. Fuck the salt (his words not mine). Anyway, he was in the process of following Cheapskate's MQ synth and was using Method 1 and after 2 and a half hours a large portion of the reactants had vaporized off. There was a lot of vaporizing going on. This most likely was not water. Water liberation was very evident I am told. The temperature was also a little below the 190C that Cheapskate recommends. There maybe a problem with the thermometer reading wrong but I don't thinks so. If anyone has any ideas or insight who has done this let me know and I will pass this on.

So my understanding is this material was then thrown into a beaker with water and there is a really nice purple mass. Water was also added to the reaction beaker. I have heard that the purification will take place later today and that this person will finally get a shot at something that has been absent in his life for years.

Let's wish him luck.

jsumner · Thu Mar 31, 2005 3:52 am

I just finished typing my long diatribe on where this synthesis stands. It took so long that it timed out and I lost what I typed. Evil or Very Mad

Please oh please mods, or admin, fix this glitch (it is a glitch IMHO). Or if it is something I have set on my computer please tell me how to stop it. It is very frustrating. I knew about this and have been copying my posts before posting and this time I forgot to do it and it nails me. Murphy's law applied. Forgive the brevity as the other post was probably longer.

Anyway, I heard where my friend's friend (hereafter referred to as " the chemist") stands on the MQ synthesis today. I know this thread is titled wrong now. I will try and change the title if it will let me. Otherwise I would ask the mods to change it for me or split the thread I guess.

So the chemist is following Cheapskate's MQ synthesis. He has met Cheapskate on a ng and was given the link to the synthesis. He is following Method 1 from the synthesis as Anthranillic acid is a List 1 chem and he doesn't feel like using twice the Acetic Anhydride that would be required to make the MQ if you made the acid from the n-acteyl anthranillic acid per the synthesis published by Rhodium. If anyone needs these syntheses PM me and I will send you the link. Though as alluded to in another post I made in the pharmacology section this is not fertile ground by any means so I apologize if I am taking up unnecessary bandwidth but this is new to me and I suspect I am not alone. I also have yet to read the threads from the Hive yet. I was not a member there and am looking forward to perusing the threads that were posted here, sort of, for download.

Anyway the chemist mixed a fair amount of n-acetyl anthranillic acid crystals, all that were obtaind from the n-acetyl toulidine to n-acetyl anthranillic step as set forth in Cheapskate's paper. He did not weigh em and had left them to air dry over night. These were placed in a beaker and excess o-Toluidine was added. The beaker was heated in cooking oil at about 170C to 180C for 2 1/2 hours. Cheapskate indicates that this can be left go all night. I disagree as I was told that he was happy he returned to the lab after such a short time as a large volume appeared to have evaporated, no it surely wasn't stolen, and there were a fair amount of fumes coming from the reaction beaker. The mp of the MQ freebase is listed as ~ 114C by Rhodium in his paper on various syntheses of this material. I do not have data on the b.p. but will look to Sigma-Aldrich as the supply even SchI in the US as diacetyl morphine can be ordered with the right credentials and a butt load of cash IMO. The street is cheaper.

So, the chemist freaked a little and grabbed the beaker from the oil. He was trying to let it cool but there were still a lot vapors evolving. He quickly looked over the procedure for the thousandth time as he has been studying and researching it for well over three months and read to throw the purple resin into water. It is amazing how you can misread something when there is an apparent crisis. The chemist had also used up all his DH20 and resulted to using tap water. (possible problem point)

The chemist had something else going on so he left this material in the water for about 4 to 5 hours. There was no mixing involved. When he got back he drained the water and added some acetone. This dissolved most of the hard sticky purple goop (resin - MQ Freebase and unreacted o-Toluidine I have been told). This was then warmed on a hotplate till it was all dissolved.

To this warmed mixture fuming HCl was added. And, like warned in Cheapskate's synthesis, the material immediately boiled for a brief moment. There was also a liberation of HCl gas at this time. This is evidenced by the noxious fumes released. This mixture was then brought to a gentle boil. The chemist had not been using his fume hood for this and this was a big mistake. With the boiling, HCl gas was constantly being evolved. I am concerned that all the HCl was evolved in this step.
(possible problem point)

The material was then placed in the freezer as the chemist was eager to purify this and give it a try. After an hour the material was removed from the freezer. I need to mention that there is also an uncovered beaker of n-acetyl-o-toluidine in there that has been recrystallized from ethanol and is waiting to be filtered. This guy has been busy and just needs to get around to it as there are about 150 grams of it to store, sealed and in a dark place of course. When the beaker was removed there were no crystals and the chemist was pretty bummed.

Cheapskate's paper mentioned this possibility and super saturated solutions are not that uncommon. So, he took a glass stir rod and dried some fluid on it till totally dry. This was then inserted into the liquid with the hope crystals would rapidly form. They did not form however. This was repeated two additional times to no avail. Could the dried fluid also be super saturated??? (possible problem point)

This beaker was then put away uncovered in a dark cabinet and let sit all night. The belief was that maybe it needed a fair amount of time for crystallization as this was alluded to in Rhodium's synthesis using Anthranillic Acid, o-Toluidine, and GAA. But today there were still no crystals.

The chemist is getting a little upset with this. First the problem of converting the o-Toluidine HCl to o-Toluidine failed miserably and he had to start over with a new supplier and no this. Hopefully you all can help me out here.

The following is what I wish to pass on to the chemist regarding possible problems:

Those are my thoughts and I hope some of you have others. I would love to hear from someone who had this same problem and solved it. If you prefer not to post that PM me. We will have never talked I assure you. I will also add my email address to my profile so you can email me if that is preferred. I just hope that there is a simple solution as I really hate to tell the guy to dump this and give it another try. I also understand that he will need to order more KMnO4 unless someone has a synthesis from household chemicals or can recommend a tried and true subsitute for this. Can the neutralized KMnO4 be recovered and regenerated. I think regeneration and solvent reuse is the way to go to minimize chemical orders and I doubt I am alone here. I really doubt that my friend's friend is in the mood for anymore failures at this time without a sucess.

I do want to add a little something here and that is that this is the second synthesis that the chemist has tried and he told me that he wonders if these are published based on actual experience as it appeared to him that they were many items left out or very simple improvements that really have to be made to these. This is his two cents and it makes me wonder how many times these syntheses are revised. Or, is this a matter of the value of experience and knowledge. Like the other day on a.d.c. there was a guy stating that he needed to get a hold of KMnO4 and diethyl ether so he could do a synthesis. He was asking where to get the chemicals. IMO if you have to ask you have no business with these chemicals. I pointed out that he might want a substitute for the ether as this is not a "safe" chemical to play with. I could just see the fire ball in my minds eye.

Thanks in advance for your help.

jsumner · Thu Mar 31, 2005 7:43 pm

I heard how it went late last night. Seems that additional HCl or the broken glass stir rod did not produce crystals. The chemist had to think and decided to go for broke and get the solvent and acid out of the resin as this had to leave a solid of some sort.

His thought was maybe this needs to be freebased first as there is no mention of problems forming crystals if the resin is first basified. So, he started a simple distillation and removed the acetone and acid. He made a caustic solution to neuralize the acid as it came over as the HCl gas was in the vapor state. The entrance to the condensor was not allowed to exceed about 110C to ensure the resin remained in the distilling flask and distillation was terminated when no more liquid was be removed. This took about 1 1/2 hours.

The flask was removed from the heat source and it was filled with white vapor. Sigma had no data on the vaporization temperature of MQ HCl but I suspect it is very close to its melting point that Rhodium published. The flask was allowed to cool. And, there it was there were areas of white crystals in the flask. The sides and bottom were also coated with purple resin.

The purification steps were then performed and no further problems were encountered when trying to recrystallize dissolved MQ HCl. The MQ salt was only recrystallized once with methanol and it is grey though I suspect another one or two times and they would be pure white. But, this guy was beat at this point. If anyone can explain this I would be most interested in knowing the reason. I have to assume that it has something to do with the aqueous HCl as with only acetone the MQ salt promptly recrystallized. I will ponder this further. Though the chemist intends to keep a little purified MQ salt around to see if this might jump start the crystallization as should happen in a super saturated solution. The rest will be destroyed as he only did this to undertake the challenge and further chemical knowledge. Wink

The yield was downright bad. By eye it is in the 5 to 10% range which sucks given the hassle encountered. I know the yield improves substantially with the addition of the water scavenger. I suspect that also limiting the reaction time will improve the yield or attach a condensor to the flask outlet to reflux what tries to leave. I also saw that one of the syntheses that Rhodium had in his paper employed a phosphorous based catalyst. If this allows much lower reaction temperatures this should also greatly improve the yield so if someone knows if this is the case I would appreciate hearing about it.

I guess that is all for now. There are some things that need to be looked into before the next run but I suspect it will not be long before I post again. I do hope to post some corrections to Cheapskate's synthesis based on what the chemist has experienced following it.

jsumner · Fri Apr 01, 2005 2:51 am

I heard from someone on a newsgroup I read and post in. This person stated that the MQ HCl crystals did not form because the solution was to acidic. This made sense after I read it as Cheapskate uses a pH 3 aqueous solution to further purify the product. For the life of me I did not make the connection until it was pointed out. Embarassed

I also understand that the chemist is no going to try and catalyze the final reaction as the catalyst is fairly expensive and he is not interested in even more liberation of HCl vapor.

I will keep everyone posted and I hope this is at least informative and not just repitition.

jsumner · Mon Apr 18, 2005 11:46 pm

Just a quick update from what I have heard. The guy said the yield was terrible. He was quite a bit bummed about this after all the trouble he went through. Anyway I understand that he intends to make use of the scavenger in his nexty attempt when he decides to make one. Anyway all is very quiet now so maybe he's sleeping.