Subject: Abstracts of MDP-2-P production From: eleusis@netcom.com (Eleusis) Date: 1995/07/07 Newsgroups: alt.drugs.chemistry 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 Example 24 ---------- Add .1 mole of 3-(3,4-methylenedioxyphenyl) propylene, .25 mole of methyl nitrite, .008 mole palladium bromide as a catalyst, .5L of methanol and 36g of water to a flask. Stir magnetically for 2 hours at 25C. 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.) Example 51 ---------- Add .1 mole of 3-(3,4-methylenedioxyphenyl) propylene, .25 mole of methyl nitrite, .5L of methanol, 36g of water, .00025 mole of trimethylamine, and .0005 mole of palladium chloride as a catalyst to a flask. Stir magnetically for 1.5 hours at 25C. 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). Example 68 ---------- Add .1 mole of 3-(3,4-methylenedioxyphenyl) propylene, .25 mole of methyl nitrite, .5L of methanol, 36g of water, .006 mole of bis (benzonitrile) palladium (II) chloride as a catalyst to a flask. Stir magnetically for 1.5 hours at 25C. 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 the reference: US Patent #4,638,094 "Process for producing phenylacetones" ------------------------------------------------------------------------ Sunlight 980611: 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. ------------------------------------------------------------------------ Sunlight 980602: 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 : Example 95 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%. and Example 94 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%. and Example 86 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.degree. 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.degree. C. for 60 minutes by adding 36 g 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 ? ------------------------------------------------------------------------ Sunlight 980608: The present post is an adaptation to kitchen chemistry of Japanese patent #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, Rhodium's page, 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 photografy supplier in the net or Alliance... Procedure is as follow : 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 : A. 50 cc of safrol, 300 cc of methanol, 2,5 grams of PdCl2 B. 100 grams of NaNO2, 60 cc of methanol and 200 cc of H20 C. Chilled solution of 38 cc of H2SO4 and 85 cc of H2O 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 cc 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 or abit more /second). 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. ------------------------------------------------------------------------ Sunlight 980915: 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. ------------------------------------------------------------------------