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MDP2P in 73% yield from safrole using PdCl2 and MeONO
In these spring nights, I often dream with the patent "Process for producing phenylacetones" (alkyl nitrite in corresponding alcohol + safrol + PdCl2 [+ CuCl2 or amine ] = MDP2P). I've dreamed always with methyl nitrite maden from a solution of NaNO2 in methanol and water and dropping dilute H2SO4. A lot of dreams with CuCl2 cocatalyst and some with trimethylamine, and never yield was the claimed in patent. Then I realised desired cocatalyst effect of CuCl2 or trimethylamine never was. Why ? I don't know. Always Pd Turnover (mols of product/ mols of PdCl2 ) was between 15 to 20, never 166 as patent claims. So I satarted to dream...
Some days ago I had a powerful dream:
1.75 liters of drugstore methanol and 6 grams of PdCl2 was bubbled with MeONO produced with a solution of 110 mL of methanol, 225 grams of NaNO2 and 300 cc of water (110 cc of H2SO4 and 200 of water, chilled was added to the NaNO2 in 2.5 hours ). With stiring, of course, and with a homemade bubbler made with a piece of glass sponge (for feet) welded to a glass tube. After the adition of about 200 grams of NaNO2, 100 grams of safrol (100 cc of single distilled safrol) was added. Catalyst was not dissolved, but the reaction went to 35-40 degrees, with a great bubbling of NO and after a while all catalyst dissapear. In 30 minutes or so reaction was done, I think, and palladium appear again, but all MeONO was bubbled, and reaction was kept 2 hours from the safrol addition. Then was added 135 cc of water (water is not good before because MeONO is less soluble in methanol-water mix, so you need more solvent) and was stired two hours more. Methanol was evaporated at low pressure, the result , with no safrol smell at all (all safrol reacted) was basified, what produced a lot of brown tar wich was filtered, and extracted with 100, 100 and 70 mL of toluene. Toluene was distilled and the ugly deep brown product was distilled at 158-165°C with a water pump and all joints sealed with silicone products to give ... 81 grams of MDP2P. Great! It is a 73% yield, and I'm sure yield is more, because my dream procedures are not exactly academic. Also distilling flask was 500 cc to distill 100 cc, so at the end, with good temperature, it was impossible to distill some residue. No safrol or isosafrol in the product, only MDP2P and more heavy products, I think these are something like pyperonyl acetic acid, acetaldehyde and others.
Advantages, no O2 cylinders, easy to done, NaNO2 is OTC or no suspicious product, methanol is from drugstore... Problems, don' forget re-direct MeONO and NO fumes out through the window with a plastic or rubber tube. Really toxic, but well done, no problem at all. After basic wash a lot of brow tar was formed (may be help an acid wash first). Also I did a an error, because most palladium was precipited in the flask, so it's time to filter and recover this product, may be is reusable (palladium or palladium complex?) but, I prefered evaporate before, and later there was not palladium free, all is in the organic layer. Finally, this the rest of this strange palladium tar is now in the distilling flask. I think is necessary to boil NaOH strong solution to clean it. But is a good dream. 100 mL of safrole (single distilled) gave 81 grams of MDP2P. It's my best one.
Great post... NaNO2 is available OTC as meat perservative no? and did I hear "stump remover" from someone?
Catalyst was not dissolved, but the reaction went to 35-40 degrees, with a great bubbling of NO and after a while all catalyst dissapear. In 30 minutes or so reaction was done, I think, and palladium appear again, but all MeONO was bubbled, and reaction was kept 2 hours from the safrol addition.
So after the palladium appeared, you stirred for two hours, then you added water and stirred for two more hours again. At the end of the rxn, is the PdCl2 in or out of solution? When is the best time to recover the PdCl2?
Not exactly. In my dream first I added to NaNO2 solution almost all the H2SO4 solution. It's important the bubbles to maximize absortion of MeONO in methanol. I think the limit is 8-10 grams per 100 cc of methanol. Then the solution has all the MeONO needed, I suppossed, what took about 1 and half hour, and safrol was added. Started a slightly exotermic reaction and the rest of MeONO was bubbled. After the addition of safrol the reaction was kept two hours, I think one hour and half is enaugh. Then water was added and stired two hours more. It's good to warm reaction a bit, if possible, but not necessary, it helps hydrolisis. Sometimes precipites palladium, normally when water is added if there is not a lot of methanol. This time, may be the most part of MeONO reacted in the first half hour, and palladium precipited. I don't know why, but I think is because there is no MeONO to react and recover palladium, some strange complex are there. Even in the patent is said that the function of nitrites is not clear. I precipitate occurs, it's time to filter. I think is not Pd metal, but Pd organic complexes. I don't know if it can be reused. May be. If you filter now, sure you avoid a great part of the tar. All safrol was reacted, and no smell of isosafrol, only ketone and other little byproduts. Sure some night I'll have a simplified dream, you will know it.
BTW, in #3, i think things are similar, the extracted phase will be deep red-brown, after basic wash a lot of precipitate will be formed, and when distilling a lot of ugly brow tar will make the falsk really difficult to clean, or not ?
The bubbler is important. It's important to get a lot of little bubbles to maximize absortion of gas. Other one. Filter after hydrolisis and before evaporation. After evaporation, with the temperature, all palladium goes back to organic phase. Sorry
Do you think it would be possible to use slightly less Pd with a longer reaction time? Say 4g/100g safrole?
And, me being likely to f*ck up several times before getting things right, can I add the PdCl2 to the MeOH/MeONO after the MeOH is saturated?? ie instead of bubbling the PdCl2/MeOH soln and possibly screwing up and losing precious PdCl2.
Sunlight: Great variation to process #3. Could you write a more simplified step by step procedure of this. I think it has great potential, just needs a little more explanation for those of us that are a little slow at grasping chemical concepts (We're chemically challenged so to speak) ;o)..
For you who don't know what he's talking about: US Pat. 4,638,094 "Process for Producing Phenylacetones"
Great one Sunlight!
You haven't mentioned temperatures. Did you keep the reaction at room temp? Did you cool the flask down when bubbling MeONO in, to maximize absorption? You how fast does the MeONO evaporate away, do you need to keep bubbling all the way through the reaction or at intervals? I would think this could be done in a pipe bomb , this way you wouldn't have to keep bubbling in MeONO.
MeONO is bubbled into chilled methanol to maximize absorbtion, add your catalyst and safrole, then let react (under pressure from the bomb) at room temp. or maybe with a bit of heat (or would you get more polymerisation with heat?) Some shaking is also needed. After a few hours add water to hydrolyize and work up. Could give you a better yield.
BTW, I like the sponge idea ;)
The alkyl nitrites can be prepared by bubbling N2O3 gas through them, a'la pugsley can't they? ie use stump remover instead of NaNO2. Stop when the weight reaches the desired concentration.
Well, a lot of questions...
This procedure is in the patent in the Osmium post. All examples will cocatalysts doesn't run (?), give yields as only PdCl2 were present in reaction. So I've tried with 6% molar PdCl2 and no catalyst, is also in the patent. What I've done is to reduce the amount of solvent, in the patent uses 0.5 l. of methanol to 16 grams of safrol. I think this reaction done as Uncle Fester SOMM with plenty catalyst will give similar yields, but make the basic wash after evaporation, becuse palladium is not in water, but in organic phase. Other difference is that I prefered to add water later, also is a variation present in patent, because I've found MeONO is more soluble if there is'n water, and yields are better. I think there's no problem with bubbling MeONO in methanol with the PdCl2, but it can be added later if you want. Also safrol and PdCl2 can be added before adding MeONO, I've added safrol later because then is a excess of MeONO and probably the reaction works better, quick and safe. but may be works the same. With a small quantitie I've tried this variation also, then I didn't distill, but the product smell nothing similat to safrol (MDP2P), what means reaction is also ok. Methanol can be chilled and so absortion is great. The problem in the absrtion question is to know when are is the flask the 2 or more mols of MeONO needed for each mol of safrol. With small quantities I weighed the flask each 15 minutes or so till the weight was the desired. So I observed absortion at room temperature, about 20°C is about 8-10 grams of MeONO per 100 mL of methanol. Also is needed some bubbler, if not, you must increase the amount of MeONO bubbled in reaction, cause absortion is slower. There are a lot of combinations. I'll try the singlest one and you will know it in a few days. I think may be is not important safrol is before or later MeONO, what is important is enough PdCl2 and enough MeONO. Also I think PdCl2 can be reduced a bit. In other reactions I've foun Pd Turnover of abut 20-25, wich means maybe 4-5% could be enough. I'll try. Just a few days. I'll post a complete recipe, quantitites, temps, time, etc... After 8 months, I'm starting to enjoy.
I'd use EtONO. Boiling point around room temperature, and better absorption. Keep the water content low, reaction will be faster. And dissolve the Pd cat. properly, it takes quite some time to dissolve completely. Use the bisulfite for purification. O. had a powerful explosion when O. tried to distill it.
Well Osmium, I know you are a great Bee, and I've learned with you . Like me, you can learn with my experience. I have dreamt with this rxn 20 times more or less, with all the possible variations I've found. EtONO, yes I tried with Eleusis and UF recipe. Boiling point is 17°C, so when you have finished rxn, separating layers, you have a mixture of sodium sulphate crystals in chilled water and in the top the nitrite, but the crystals don't pass through the hole in the sep funnel. So EtONO starts to boil in a few minutes. I got stoned and intoxicated. MeONO runs OK, and is done in situ, less time, less work. No water, it increases solubility of MeONO in methanol. After water to hydrolize. 6 grms of PdCl2 couldn't be dissolved in 1.75 liters of methanol in about 2 hours, but this is not a problem, catalyst don't need to be dissolved to react, I've seen how it react and dissolves during rxn. You are the second person that reports an explosion distilling product with this rxn. I've distill it six or seven times with no problem. Only that when PdCl2 was 0.5% or 1% or 2%, most part of distillate was safrol and others, with 6% all is ketone, but always the flask needed a hard work to clean. Otherwise, bisulphite is a good alternative. You can help me now, once I dreamt with bisulphite addition and it yielded 7 grams. I put it in 10% NaOH and shaked it, but there wasn't two layers, but a strange emulsion, like ketone didn't want to go out. How do you do it ? May be is better adding HCl and don't breath fumes?
NaOH is much better than HCl. Extract it.
Sunlight: have you ever heard of Uncle Fester's "Secrets of Methamphetamine Manufacture". Your so-called new method was long ago described by Uncle Fester, so actually you're sort of stealing it from this guy, aren't you? Sure, it is the best way to convert safrole into MDP2P, but Uncle Fester has given instructions following the patent. The only new thing he came up with was bubbling methylnitrite into the reaction mix instead of making the nitrite first and adding it in liquid form. That's why your yields are low! That methylnitrite is so freaking volatile, you'll lose most of it before it reacts so you have to use a 2-3 molar excess. Substiting isopropanol for methanol gives a nitrite that is easier to handle and gives higher yields at 30°C. Well, if that's what it takes to get in Strike's book, I have a good "NEW" method which embraces electrochemical epoxidation of isosafrole and then isomerisation to the ketone with LiI... interested? Lr/
Has anybody tried this with isopropyl nitrite? It would seem that this would be even easier to work with than EtONO, since you'd think it would have an even higher boiling point. However, what would happen with steric hindrance, etc.? Any ideas?
IPA seems, theoretically at least, to be the alcohol of choice. The nitrite produced had a boiling point around 40°C, so it could easily be distilled. The distillate could then be simply poured into the reaction flask. Less solvent would be needed, so larger batches wouldn't be as limited by the avaiability of oversized reaction vessels. On top of all of this, due to its ease in transportation, it would make a great substitute for poppers!
Does anybody have any feelings about this?
Say, what if you used IPA to make the nitrate, then poured it in like Labrat said, then bubbled the exhaust from the reaction flask into a bucket of NaOH or something. Would this be a clean enough process to be done in a bathroom or kitchen?
When using ethyl nitrite, it can be generated in a external gas generator and distilled into the reaction by placing the generator in a warm water bath. It will dissolve in the alcoholic solution very well. Using IPA-ONO doesn't avoid problems, at least when the reaction solvent is MeOH. In alcoholic/MeOH solutions both nitites, that of MeOH and that of IPA, will be present.
Labrat: I think I haven't said this is a new method. And you can read in one of my posts:
I think this reaction done as Uncle Fester SOMM with plenty catalyst will give similar yields, but make the basic wash after evaporation, becuse palladium is not in water, but in organic phase. Other difference is that I prefered to add water later, also is a variation present in patent, because I've found MeONO is more soluble if there is'n water, and yields are better.
I started with SOMM, of course, but with the prefered method as UF say, what means a 0.5% PdCl2 and a 2.5% CuCl2. Well, this method yields about 3% MDP2P. Also trimethylamine was tried, and a lot of variations since I understood may be the problem is in PdCl2 amount. I have read never a post with good yields in this method, so I posted my dream. Just because I want all the bees to know what really runs, and what doesn't run. As a contribution, not as if I were a great chemist, what obviosly I'm not. What about methyl nitrite? I buy methanol OTC, and is one step reaction. Yields in patent are 91% but analyzed before any extraction. I said I have losed some materials with my poor methods. For me 81 grams from 100 mL of safrol is the best I have done never. May be it's usual for you, but not for me. What we need is real reports, what I want is to share what I have found with the patent/SOMM method. May be you like to compete, but I prefer to learn what is single and easy. And safer. Don't compete, but collaborate. We all are one.
Labrat: I want to explain you somethings about SOMM. As I've said, I started with the cheaper method in the book, wich definitively don't run. Fester say is the best. I asked Fester about this, but he couldn't say anything, because he hadn't done. I know also some people who have tried it, and after some attempts, they abandon. Fester is wrong in this point. Well, I had then a lot of questions about why is the reason rxn didn't run ok. I thought about absrtion of methyl nitrite, so I started to dream with small quantities. To be sure, I decided to put first nitrite , weighing the exact amount of nitrite before adding safrol. But rxn didn't run. Now, with a quantittie I can't weight, it's the same to make this in one way or in the other, both are good, and I must say you in the rxn I've dreamt, all safrol reacted, 100 %, yield is not low for this reason. Also I'm sure yield was higher, but evaporation, washings, filtration and distillation in a too much large flask, obviously means less product. I thought sometimes this rxn is wrong and never yield nothing. I know other people who have tried with no results and they abandon as I've said. I finally realised that rxn runs, but depends only of PdCl2 amount. Cocatalysts effects don't run, unfortunately. If you, or other bee can discover how to do it, it would be fantastic. 1 gram of PdCl2 and 4.25 of CuCl2 for 1 mol of safrol. So I tried with 6% catalyst, first with a test. I bubbled then nitirte into safrol - methanol .Yields were good. Fester is right now. After this, I dreamt with 100 cc of safrol. Then I decided to put first nitrite. Why ? Because was the only way to know all nitirite is in the flask, and I have reasons to doubt about Fester's procedure. To simplify, next try will be bubbling into safrol - methanol. So, what I'm saying is that rxn with plenty catalyst runs, what was very doubtable for me and for others. I have never heard this rxn runs, only people said rxn doesn't run. It's easy, and I think what I say it's interesting. Fester's procedure is intelligent, so I use it. But Fester don't know exactly the reaction. For example, palladium is in the organic phase. If you don't wash it with dilute NaOH you will have a lot of palladium in the distilling flask, two person have reported an explosion in distillation, may be for this reason. Fester procedure is partially ok, not completely. There are many errors in SOMM, so it's interesting to clear up things. May be all people know this rxn, may be this report is unnecessary, then excuse me.
Mr X: Yes, chilled methanol increase (of course) absortion of MeONO, Ive done it. Working with small quantities it's possible to weight absortion. But I want to try a general method. As Fester, but tested. If you don't have enough NaNO2, chilled methanol reduce the amount needed to ¾ parts more or less.
OK Sunlight, it's a good thing you tried the patent procedure and found out things didn't run as was stated. That's always a good thing. Practical experience is about as valuable as a new theoretical procedure. But what really pissed me off yesterday was that you practically copied Fester's method out of "Practical LSD Manufacture"! It was even more distressing to me, cuz I wanted to post some more on this reaction too. Fester presented this reaction as was it something new. It's not new and known for a long time: it's called the Wacker-process. This process is used to make acetaldehyde from ethylene. The patent is new in the aspect that it covers an alcoholic Wacker process, with an alkylnitrite as a reoxidant for the palladium salt. I have some pretty good refs on Wacker oxidation wherein a lot of good theory is worked out in detail. But since you posted on this subject first, you get the credit for it and I will not elaborate further. Damn shame for all the work I put into it. Now you gettit why I was a bit cranky? Good.
Sunlight: In your many dreams have you tried using straight sassafrass oil?
No, never. Safrol is single distilled, wich is a single procedure if you can distill. May be it will run. Otherwise, if you can't distill (with a water pump in this case), you will have a problem with the ketone because is plenty of Pd byproducts. When this brown product is in aluminium, impurities can stop rxn and you must add then a bit of NaOH. It runs, but you must purify your brown honey recrystallizing a few times. (Hot acetone or hot IPA and then acetone).
Of course distillation is better, or as Osmium say, bisulphite recovery. This might do skip both distillations...
Sunlight: Could you please clarify a few basic points;
In setting up this rxn, you added the Methyl alcohol + PdCl2 to a 3-4 liter flat bottom flask and started stirring? Best to use 2 neck flask; one for addition of safrol the other for gas dispersion tube (bubbler)? Does temp need to be monitored?
Then set up a gas generator to make the MeONO gas in? The PdCl2+MeOH is stirred and to this solution you bubbled in the MeONO gas?
The Methyl alcohol (chilled)+NaNO2 was dissolved and was added dropwise to the dilute H2SO4 at the medium rate (to create the MeONO gas)??. How did you tell when 200 grams of NaNO2 was added? Since it's in solution with the MeOH? In any respect the gas generated was bubbled into the alcoholic PdCl2 solution. When approximately 4/5 of the alcoholic NaNO2 was used up (added to the H2SO4), you add the safrole?
How long did it take to bubble that much MeONO gas into the solution? After the safrol you stir for an additional 2 hours (then hydrolyze with H2O)?
Please wait till next week. I've had another dream, but this time bubbling MeONO directly in safrol+PdCl2+methanol, as the patent say, and Fester. It also works and is easier, I put safrol after nitrite because I wanted to be sure all nitrite is in rxn when safrol is added. In this new rxn, 150 cc of safrol are in 1.75 liters of methanol and 8.5 grams of PdCl2. Then was bubbled MeONO produced with 280 grams of NaNO2. 2½ hours, (no safrol in rxn, smell different , funny!) then 200 cc of water was added. I must distill now, but I'm sure I have more than 120 grams of ketone. Also I've realised when 5 or 6% catalyst is present in rxn ( is my third attempt, first one with 16 cc of safrol ) MeONO reacts very quick, solvent and NaNO2 can be reduced more. But it will be my fourth dream. Till next week. May be I can find a translator to express me better. It's a hard work.
Sunlight: Nice one man. That is a very attractive route. I notice that you use more water & less methanol than Fester. Is there a reason for that? As Osmium alluded to, can the ketone be seperated with bisulphite? If you arn't bothered about recycling the catalyst and just want the product... I wondered about cooling & filtering the product mixture, adding water & bisulphite then filtering again, throwing out the junk...
I notice that you use more water & less methanol than Fester. Is there a reason for that?
As Osmium alluded to, can the ketone be seperated with bisulphite? I wondered about cooling & filtering the product mixture, adding water && bisulphite then filtering again, throwing out the junk...
I've made bisulphite addition when product is isolated, with no distillation. Of course it runs. I've also thought as you about to add directly saturated bisulphite solution to the reaction, but I haven't done, Two reasons, first is I don't know what is solubility of bisulphite in methanol, the other is I think that when Na in solution, as bisulphite is a weak acid, this will make hydroxides precipitate as tar (just as basic wash) but I don't know. As you see, there are a lot of ways to investigate. I don't like distill at low pressure, but seeing these brown products I am surrended. Let's go on...
I have just done some reading and have a few suggestions for you all to throw around...
These ideas are just that. My angle is 'just how simple can this reaction be made'.
Oh yes, I also thought about those nasty nitrogen oxides in terms of N2O3... Maybee the pseudonitrosite is being formed. This would certainly form a nasty tar. Again, maybee a little water in the methanol/nitrite solutiion might be good ? Check out Rhodiums site for a good overview of these nitrosites.
1. Sunlight adds his water after all the safrole has formed an intermediate. I suggest that this may lead to more polymerization since there will still be some nitrites & nitrogen oxides in the brew and these are quite reactive compounds. This leads me to...
Well, patent says it will give higher yields.
2. I have read that you must distill off the methanol under reduced pressure because of the nitrites & nitrogen oxides which screw around with the product. Can these compounds be destroyed in some simple fashion ? These are most likely the compounds that explode.
I haven't had never explosions. Nitrites and NO fumes goes out easily when adding water and when adding vacuum. Explosions have been reported distilling product. If you don't wash you will have a lor of tar, may be it's the reason.
3. I am guessing that sunlight is from europe. If so, amyl nitrite can be purchaced from head/rave/sex shops. If you buy in bulk, it is quite cheap. This has a B.P. high enough to prevent fumes being a problem.
Good observer. I'm from Europe. But I don't want to buy any chemicals, only OTC and the minimum amount of otheres. Amyl nitrite is a "strange chemical" for a normal citizen, and requires amyl alcohol, wich is other chemical. And it's no really cheap. Fumes are not a problem if you do things right.
4. what if you added hydrogen peroxide instead of water ? I don't know but maybe it will form less dimers etc.
5. If you CAN remove the dodgy nitrogen compounds, can you just add bisulphite to the methanol
Maybe, but I have only nightmares with bisulphite (metabisulphite).
These ideas are just that. My angle is 'just how simple can this reaction be made'.
See last version, I think it's the best and simple to get more than 70% yield, (>80% in weight from safrole).
Oh yes, I also thought about those nasty nitrogen oxides in terms of N2O3... Maybee the pseudonitrosite is being formed. This would certainly form a nasty tar.
Yes, some tar may be this kind of products. Patent runs as I do, and yields are enough good. I think also Pd reaction is quicker than nitrosite one, so, equilibrium of reactions is clearly in the side of Pd oxydation.
Various Preparations of 3,4-Methylenedioxyphenylacetone
In all examples that follow, the same basic procedure was used. Unreacted starting materials, solvents, catalysts, etc... were stripped from the product through distillation at reduced pressure. The product can be separated from non-distilling residuals by extraction with ether. The palladium catalysts can be recovered in most instances, but eventually they do succumb to the reaction and must be replaced. Standard lab practice applies, see Zubrick or Vogel if you are unsure.
A unit specified in some reactions is the "Pd Turnover Number":
Formed molar quantity of product Pd Turnover Number = ---------------------------------- Charged molar quantity of catalyst
Add 0.1 mole of 3-(3,4-methylenedioxyphenyl) propylene, 0.25 mole of methyl nitrite, 0.008 mole palladium bromide as a catalyst, 0.5L of methanol and 36g of water to a flask. Stir magnetically for 2 hours at 25°C. Yield of 3,4-methylenedioxyphenylacetone (also known as 3,4-methylenedioxyphenyl-2-propanone/MDP-2-P) is 95% with 100% of the reactants consumed.
(My note: the water is in molar equivalence to the reactants, but the methanol is not. So if you wish to scale up by 10 times, you should only have to double the amount of methanol to get a nice solution.)
Add 0.1 mole of 3-(3,4-methylenedioxyphenyl) propylene, 0.25 mole of methyl nitrite, 0.5L of methanol, 36g of water, 0.00025 mole of trimethylamine, and 0.0005 mole of palladium chloride as a catalyst to a flask. Stir magnetically for 1.5 hours at 25°C. The conversion of the starting material was 92%, the yield of MDP-2-P was 83% and the Pd Turnover Number was 166.
(same note applies as above, but do not alter amine concentration).
Add 0.1 mole of 3-(3,4-methylenedioxyphenyl) propylene, 0.25 mole of methyl nitrite, 0.5L of methanol, 36g of water, 0.006 mole of bis(benzonitrile)palladium(II) chloride as a catalyst to a flask. Stir magnetically for 1.5 hours at 25°C. The conversion of the starting material was 100%, the yield of MDP-2-P was 88%.
(same note relating to methanol conc.)
There are several more highly similar examples presented which test variations in reaction order, catalyst type, etc.. I picked the first three I came across which yielded MDP-2-P.
For further information, see US Pat. 4,638,094 "Process for producing phenylacetones"
Well, Eleusis is wrong (I think), when he said in Example 51 "do not alter amine concentration", because the patent says the amount of amine depends on amount of PdCl2, and solvent is independent of them.
I don't know why, but unfortunately, noone we know had good yields using a cocatalyst with PdCl2 as CuCl2 or trimethylamine. I've dreamt about this two procedures several time with both cocatalysts, and at least I realised yield depends only of PdCl2. So I suggest you that replace the examples of your board with this one, that runs OK:
The reaction of Example 94 was repeated, except that 3-(3,4-methylenedioxyphenyl) propylene was used in lieu of 3-(4-methoxyphenyl) propylene.
As a result, the conversion of the starting material was 100%, the yield of the intermediate 1-(3,4-methylenedioxyphenyl)-2,2-dimethoxypropane was 92%, and the yield of the desired 3,4-methylenedioxyphenylacetone was 91%.
The reaction of Example 86 was repeated, except that 3-(4-methoxyphenyl) propylene was used in lieu of 3-(4-hydroxyphenyl) propylene and the hydrolysis time was changed to 30 minutes.
As a result, the conversion of the starting material was 100%, the yield of the intermediate 1-(4-methoxyphenyl)-2,2-dimethoxypropane was 94%, and the yield of the desired 4-methoxyphenylacetone was 93%.
A 0.10 mole amount of the starting 3-(4-hydroxyphenyl) propylene, 0.25 mole of methyl nitrite, 0.5 liter of methyl alcohol, and 0.006 mole of a palladium chloride catalyst were charged into a reaction vessel. Then, the reaction was carried out at a temperature of 20°C for 1.5 hours.
After the completion of the reaction, the reaction mixture was gas chromatographically analyzed to quantitatively determine the unreacted starting material and the resultant intermediate product (1-(4-hydroxyphenyl)-2,2-dimethoxypropane). As a result, the conversion of the starting material was 100% and the yield of the intermediate product was 85%.
The reaction mixture (containing the intermediate product) obtained above was hydrolyzed at a temperature of 20°C for 60 minutes by adding 36g of water. After completion of the hydrolysis, the desired 4-hydroxyphenylacetone was quantitatively determined by a gas chromatographical analysis. The yield of the desired product was 84%.
You can make one with this three.
It will be wonderful to work with 0.5% molar ratio PdCl2, but... Anyone knows why cocatalyst effect don't work?
The present post is an adaptation to kitchen chemistry of US Pat. 4,638,094, process for producing phenylacetones, and is the result of a large battery of dreams.
In SOMM (Uncle Fester), we have three versions of this patent, one uses PdBr2, other PdCl2 and the "prefered" uses PdCl2 and CuCl2. Last one doesn't run. Also SOMM version be dangerous because in the scheme of rxn, Fester lets 6 mols of NO and nitrites to go out free of rxn vessel (see "Eleusis vs. Fester", Eleusis it's right). Well, both gases are very toxic, good ventilation is not enough and these gases must by carried out of the window through a tube (use a two hole rubber stop or a two necked flask). Also in this sample a precipitate that is taken out, these are undesirable byproducts, also washes must be done when rxn is done to liberate as Pd as possible. Two explosions have been reported when distilling, may be because this reason. Also in this procedure we spend much less solvent, minimizing evaporation time, less catalyst and less NaNO2.
Otherwise, I agree Uncle Fester his work because he have shown me a lot of things, I recognize also the good part of his work. Interest of this reaction is that uses OTC chemicals or non suspicious, as NaNO2 (it's used in food industry as a conserver), and it's really easy. Methanol used is drugstore methanol, PdCl2 is from online photography supplier.
Procedure is as follows:
A solution of chilled dilute H2SO4 (C) is dropped in a solution af methanol, water and NaNO2 (B), then methyl nitrite is generated, and bubbled in a solution of safrol in methanol containing PdCl2 catalyst (A).
This example has been done with good yields:
C or a part of C is put in a sep. funnel wich is connected to flask containing B (wich can be a bottle), and a tube connect this flask to the bubbler into flask containing A, wich have other tube to redirect NO and nitrite gases. Flask A is in water bath to keep rxn temp between 20-30°C (reaction is slightly exothermic) and stired magnetically. MeONO is bubbled in A with a bubbler that provides little bubbles (not necessary a gas difusor, but a single tube is not enough, you must increase then B and C). Bubbler is all deep as it is possible.
We start rxn, one drop/second or so C in B. Sometimes we close sep funnel and shake flask B to ensure a constant rate of MeONO generation. Addition speed is limited by equilibrium of pressure between flasks. If it is too much quick, then MeONO gas go through sep. funnel, then we close the sep funnel and wait a bit till generation is low. The addition of C in B takes 1 hour, we close sep funnel and shake a bit B to finish reaction. If rxn (A) climbs temp too much, we can add ice in the water bath. I've monitorized temp touching a part of solution that was out of water bath. At the final part may be water is to much cool, so we can take it out. After the addition of C in B we wait one more hour.
Now we open flask A. We can put a piece of glass and smell it once methanol is evaporated. There is no safrol smell, it's different, it's the dialkoxy derivative of safrol, rxn is completed perfectly. We add now 75 mL of water and stir 45 minutes more. There's a precipitate. We filter the reaction. I don't know what is this, may be also black tar, I thought this may be palladium complexes, this is a organic compound that burns easily and may be contains Pd. This will forme tar later, now we don't have it. We can now smell another time rxn. This smell is ketone, we have more than 80% of MDP2P (patent says 91%). Good extraction procedures will give better yields. This is my version, but may be better done.
First one, evaporate methanol, better with vacuum. Then we have two layers similar in volume, we add 100 of solvent and 50 cc of basic solution (sodium carbonate, bicarbonate or 10% NaOH ). We shake it and may be we will have little more precipitate or tar. Also may be we can't see separation, then we add a bit more solvent without shaking to see separation. We make two more extractions with 50 cc of solvent. Even if we can't see separation, we can add enough HCl and shake, this will forme some tar and layers will be distincts, so we can separate and make a basic wash. Sometimes I've done first an acid wash, but I can't sure it's better.
I'm thinking now may be is better to do all extraction as Strike's top #3. Add acid solution, like 250 cc (less PdCl2 and no CuCl) 15% HCl, extract and make a basic wash. This procedure has been tested for a lot of bees and conditions are similar. Distill solvent and distill ketone with a water pump. My yield, 41 grams, about 75%.
Scaling. Of course. This procedure have been done with 150 cc of safrol, but with 1.75 L of methanol with similar yields, so I've preferred to present this version wich is better (less solvent, less time) Addition of nitrite was done in 2.5 hours. When scaling, water in B can be decreased if we have problems with our volume flasks, but this means a lot of NaNO2 is not dissolved, so each 15 minutes, we close sep. funnel, and shake B a bit, and when there is no foam, we can open sep. funnel again (1 drop/second or a bit more). My opinion is 150 is ok, but theorically you can scale more. More time rxn is not a problem for product.
Bubbler. I've done it widening the end of a glass tube, then putting in the hole with pression a piece of glass sponge (for feet) and welding it with a flame (Bunsen). When done, you can blow through it in a glass with with water to see there are many bubbles. It's enough.
Flasks. Flask containing B can be a bottle. A is a round bottom flask, it's better because in a bottle or a flat bottom flask, PdCl2, wich is not dissolved in methanol until it reacts, could be in the corner of flask without reacting.
Hazards. If you add two much quickly C in B, MeONO goes through sep. funnel. So close the key, but if there was too much addition or you shake immediatly then generation is higher than the possibilities of bubbler, and rubber on flask B can jump with a lot of foam and solution. For this reason it's better to have NaNO2 dissolved , to prevent surprises, but it's not necessary. Be patient and shake. Don't forget redirect NO and MeONO fumes out to the window.
Cleaning flasks. Flasks, specially distilling flask are really dirty, with a brown black semisolid tar. It's easy to clean them. Make a 25% or stronger NaOH solution (from drugstore, of course), put it in the flask and heat, till boiling if necessary, all tar go out easy. Use gloves, please.
Bisulphite. My personal nightmare. I use metabisulphite, what I think it's the same. Sometimes product is unfilterable, other one couldn't be recovered with NaOH solution. Investigate, I'm not a great chemist.
Solvent, NaNO2 or PdCl2 may be can be reduced, but I think the quantities in this sample are really good. Solvent is easily evaporated, NaNO2 could be only slightly reduced and PdCl2 is about 4.5% versus 6% in patent, but it's enough because all safrole reacts.
After some dreams with a methyl-nitrite generated ketone, I must honestly correct the yields I reported. Yield was between 70-75%. This ketone was distilled with single distillation, and it was too much yellow, you know pure ketone is pale wellow. I was dreaming in the amination of this product, Al/Hg reduction with aqueous methylamine in ethanol. The expected yield of this reaction would be 60-70 or even 80%, but real yields were always between 45-55%, so starting with 30 grams of MDP2P a normal yield was 20 grams of the amine salt. I think the ketone was not too much pure, may be 75-85%, so real yield from the ketone synthesis was probably between 50-60% instead of 70%+.
I think noone is dreaming in this kind of work, with similar yields it would be preferable to work with other way that needs less catalyst and less chemicals, but I must communicate this.