==================================================================== ========= Chloro/Bromo/Iodosafrole Synthesis Notes ==================================================================== ========= Endo1, September 27, 2002: I have not seen a bromosafrole post in a while so here is a detailed write up of SW's bromination variation. I like this variant because very little HBr fumes are produced, not much labour involved and the yields are nice. The drawback is it requires tech grade HBr in GAA. To a small "gem" jar is added a stir bar, 500 ml of FREEZER COLD technical grade 33% hydrogen bromide in glacial acetic acid and 325 ml of sasafrass oil (unknown safrole %) in that order. The jar is promptly capped tightly and shakin until homogenous. The reactants are then placed on a magnetic stirrer inside of a deepfreeze and stirred vigorously for 24 hours (take care that the stirbar is not stuck to the inside of the lid!). The contents of the jar are allowed to defrost just enough to pour if solids have formed and then they are poured in to a large sep funnel containing about 300 grams of crushed ice. Sep funnel is occassionally agetaded until ice is all melted. Organics are extracted with 1250 ml of toluene and the acid water layer is discarded. The toluene/bromo mix is then washed with 500ml of water and a little baking soda is added if necesary untill a clean seperation of the water and organics is observed (carefull of foaming and pressure build up). The water layer is drained and discarded. 500 ml of fresh water is added. Baking soda is added slowly with swirling and venting and then, eventually, shaking and venting bewtween adds of baking soda untill saturation of water is observed by a small amount of undissolved solids. water layer is discarded and a second "baking soda wash" is performed in exactly the same way as above. Solvent is distilled off under aspirator vacuum and recycled (see footnote 1). The
next 2 fractions are distilled off also under aspirator vacuum (see footnote 2) and then the bromosafrole is distilled under vaacuum pump reduced atmosphere to give about 350 grams of fairly clear bromosafrole. footnotes: 1: The toluene may contain some HBr so it is re-used only for the same purpose. 2: It seems fairly evident that there are two main fractions after the toluene and before the bromosafrole comes. A tiny bit of unreacted safrole at 110 and then something else at about 130-140 under SW's aspirator vaac, it's got a red tinge to it and is fuming a little bit of HBr and smells kind of sweet/irritating, maybe isosafrole or brominated isosafrole? xxx/HBr azeotrope? Whatever it is, SW thinks that this stuff is what turns some peoples bromosafrole red and is kind of hard to seperate from bromosafrole. It seems the only time SW's bromo has a red color to it is when he collects his bromo too early. Other Notes: - Keep in freezer if a wash/distill cannot be performed immediately. - Attempts have been made to use homemade HBr in GAA but problems occurred due to the high mp (the shit kept freezing up bad!) Although the mp listed in the MSDS is +17c (I think.... hmm why is it higher than just strait up GAA?), for some reason the technical grade obtained by SW never freezes in the freezer if the container is not opened i.e. the factory seal is not broken (The 500ml bottles of tech HBr in GAA are obtained from supplier). Also, very little freezing occurs during the reaction when tech grade is used for some reason. - Sorry, not sure exactly what temps the reaction actually runs at. Just a regular old deepfreeze. Maybe about -5c? - Attempts have been made to use a flat bottom erlenmyer flask to do the reaction but the stirbar created too much heat and or the stirrer transferred too much heat so the concave bottom of a jar was found to be more suitable. ------------------------------------------------------------------------------hsark:
I have distilled bromosafrole lots and lots of times. The problem is that in the end of the distllation you tend to get a volcano of black ash and smoke even if you are careful. I've been wanting to say this for a long while the 33% HBr in GAA is the best to use. You can get 90-95% yields in 12-16 hours, and you can just leave it in the freezer, although an ice chest with lots of ice works just fine. When you distill it, just be ready to disconnect it and have something to dump it in. And whatever you do save whats in the recieving side. Mainly i used to buy the 33% HBr in GAA from a chem supplier, but I also bought anhydrous HBr gas in cylinders and would make the solution myself. Both worked great, but I dont know how easy it is to aquire some nowadays - I dont have that problem. At around 20mmHg the bromosafrole would start distill at 175-185∞C and continue to rise slowly until it reached 212∞C, where decomposition occurred. I generally would stop at 205∞C, but sometimes it decomposes even if you're careful. I suggest you to be prepared, and check for vaccuum leaks very carefully. Bromosafrole is generally a clear, reddish-brown sweetsmelling oil. The proportions were 1L 33% HBr in acetic acid to 450ml safrole. Ritter: I've distilled quite a bit of bromosafrole myself, and can tell you that a higher vacuum will prevent that rapid charcoal-decomposition-volcano from occurring. The decomposition is occuring because the still pot is getting WAY too hot. When you only have a few ml's left in the still pot (about 50), cool it down and transfer the remaining liquid to a smaller 100ml flask. This should allow distillation of the last traces of bromosaf without a problem. ------------------------------------------------------------------------------Here is the only bromosafrole (or bromo propenylbenzene) synthesis you will
ever need. It proceeds totally anhydrous with pure reagents, and generates no obnoxious fumes to give you away. More than likely, this will spur DEA to add new watched chemicals (like what isn't watched already- air, water ?) To 100 ml of chilled DMSO add 7.8ml conc. H2SO4 (i.e. drain cleaner). To this add 30g of NaBr. Stir well and repeatedly. Solution will turn orange as all the NaBr is turned into Na2SO4. Do not filter, leave crystals alone in case there is some unreacted NaBr left. If the H2SO4 and DMSO is anhydrous, so will the HBr be anhydrous. Add 5 ml of sassafrass oil. Or scale qty of everything up for more sassafrass. Let sit at room temp. Don't bother to filter out crystals, in case there is unreacted NaBr. In 1 or 2 days solution will proceed as in Fester's turning green, then purple, then gradually burgundy. To understand why this works so well, see Fieser and Fieser "Reagents in Organic Synthesis" under DMSO monograph. Note that there are two pathways for HBr to react. Via an ionic mechanism generates the desirable compound. Via a free-radical route forms terminal bromo compound, which cannot be used (you can try for interesting analogue, but who cares now that all mind altering chemicals are illegal under the Analoges Act, including all those in everyone's brains- imagine, even Jesse Helmes committing felony if he has any brain cells left). The crude sassafrass oil contains eugenol, a phenolic compound which inhibits free radical reaction. Thus you will get better product if you don't purify out safrole. Also keep reaction mixture away from air and UV light, both generate free radicals. The final mixture gets 500-1000ml of water added. The crude bromosafrole which settles to the bottom is seperated without adding any organic solvent. If you cool it it gets pretty sticky and syrupy so the water layer can be just poured off. Then you add 200ml of ethanol and a 5g tablet of hexamine camping fuel to
start the Delepine reaction- you get MDA as the end product. (Well, if you like MDMA better you can do the tedious methylamin synth in Festers book or Org. Synth. Look out for methyl formate which is deadly insidious poison like dimethyl sulfate) For the Delepine reaction you can use the bomb or reflux overnight, which definitely works. some experimentation is needed here since I still am unclear as to how much time this takes, or if it really can be run at room temp. The reaction with the iodo intermediate can certainly be run at room temp, but that requires a conversion to the iodopropenylbenzene comp with NaI and maybe phase transfer catalysis or insitu with NaI during the bomb or reflux. When the hexamine salt is prepared in solution, then some HCl is added and again refluxed overnite. again, possibly this can be run at room temp over several days- who knows? Then use typical amine seperation to get the pure product from the acidic mixture. Love and trips, Wednesday. ==================================================================== ========= Several months ago someone (Pugsley, Wednesday, Uncle Fester or someother Adams family member- my connections indicate they are probably all the same) posted a synth for bromosaftrole utilizing the conversion of NaBr in DMSO with conc H2SO4 and further info for converting the bromo compound to MDA using the Delepine reaction with hexamine (camping fuel tablets :) :) ! Also, there were some negative comments from some narc (chem baiting) who disparaged the small amounts of sassafrass oil that were called for in the reaction, implying the process wasn't useful in production qty's, and
implying the hexamine reaction was some sort of joke. (prob. some community college grad in the DEA) We have done some experimentation with the bromination procedure; and although not alot of detailed info was originally given, we feel that alot more attention should be given to the potentially revolutionary procedure. First, 30g or so of NaBr was to be reacted with the theoretical (for HBr product) amount of conc. H2SO4 in 100ml anhydrous DMSO; and then adding 5ml of sassafrass oil to the resultant crude mixture of HBr and NaSO4 in the resultant DMSO solution. Objection to the procedure was the high amount of DMSO that was required in the reaction for the small amount of oil. Evidently, criticism was of the premature narc oral ejaculate before you experiment variety, since we found that only about 5g of NaBr dissolves in the DMSO anyway- but that 30g (and much more...) of NaBr reacts without the whole mass first dissolving in the DMSO. Evidently, the higher solubility of NaBr vs. the NaSO4 product drives the reaction so that all the NaBr is converted to HBr without the total amount being first necessary to dissolve. As the author notes, the first "Reagents in Organic Synth" book explains the unusual solubility and reactivity of inorganic halides and other compounds in DMSO. The solution does gradually turn orange, and magnetic stirring accellerates the process, and undboubtably converts most of the NaBr into HBr. Since some NaBr might be trapped within a shell of NaSO4, some sort of stirring is neccessary to break up the undissolved mass. ****We will next try NaI, but wanted to get this out as it may be a few weeks until we can safely procure some NaI (thanks alot, cranksters, for making anything with -I- suspect, NaI, HI, whatever, ha ha)**** In conclusion, it appears that practically any reasonable conc. of HBr in DMSO can be obtained (up until the point of heavy fuming) with the
method. Further, the enhanced reactivity of halides in DMSO and the inherently anhydrous nature of the procedure and lack of mess and fumes make it, at least for the time-being the method of choice for bromination of substituted allyl-benzenes. ................. Postscript: Although we are interested in MDMA only, the use of the Delepine reaction for making MDA is a valid method. In fact, the original post is the first time we have seen the reaction used in any underground chemistry texts. The narc called it "cute", but in fact the Delepine reaction has the cleanest and highest yields out of any reactions for converting an organic halide into a primary amine. (assuming that camping fuel tablets contain some small amount of inert binder with a majority of hexamine, there's no reason that they couldn't be used for the Delepine reaction) We would be very interested in hearing from any parties who have done the experimentation required for evaluating the conversion of bromosafrole or other brominated allyl-benzene compounds at *room temperature* as the post speculated upon. *Room temp reaction of the bromo compound with hexamine (camping fuel tablets) and further room temp cleavage of the hexamine salt (HCl in alcohol reaction) would make a complete synth that could be carried out in the complete highly desired "mayonnaise jar" glassware set for the masses*. Also, the use of sassafrass oil instead of pure distilled safrole might very well provide higher yields (although not tried here). Its well known that phenolic compounds inhibit the formation of a-bromo side reactions that occur via the free-radical process (March, "Advanced Organic Chem", and many others); and sassafrass oil has plenty of phenolics including eugenol in high conc. the Professional.
==================================================================== ========= Subject: From: Date:
Re: Re: MDA from MDP2P "guest"
1997/11/08
> Man, this has to be some of the most confusing research I've done. > Could someone (Eleusis, maybe....) tell me exactly which method for > brominating safrol with 48% HBr actually works. My #1 so far seems to > be starting with MDP-2-Pol and brominating like Fester told us way back > when chemistry worked differently (apparently). This would seem to > drive the reaction towards the bromnation side, due to the willingness > of that alcohol to leave in place of Br. > So c'mon, gimme some insights. Why don't you try doing a bit a basic research? Visit a library. In the library you will find books that you can read. When you've discovered how it's done you can post your results to a.d.c for the rest of us to read. You can connect to www.deganews.com and read old Eleusis and ZWITTERION posts on this topic. I include a couple below. Otherwise you'll have to contend with me taking the piss out of you. And when you've made your halo-safrole what next? The yield of MDMA from halo-safrole is shit because the main reaction is the elimination of HX to give you the alkene (safrole) back again! If I had MDP-2-Pol then I wouldn't want to brominate it at all. I'd oxidise it to MDP-2-P and reductively aminate the ketone to MDMA. If I wanted bromo-safrole I'd make it from safrole using a phasetransfer catalyst to allow non-polar safrole to mix with polar aq. 47% HBr. More likely, I'd use aq. 37% HCl or, I presume, even aq. 32% HCl would work to give chloro-safrole. See: Addition of hydrohalogen acid to alkenes: Landini & Rolla, JOC 45, 3527, (1980). JOC = Yes, that's Journal of Organic Chemistry to you. Phase-transfer catalysts can be extracted from hair and fabric conditioners. The cationic surfactants mentioned on the
ingredients of such stuff will easily suffice as phase-transfer catalysts. But remember, when you use a surfactant to mix two immiscible phases you must stir them at 500 rpm or better, otherwise nothing will happen. Keep the temperature on the low side otherwise you'll zap that delicate methylenedioxy bond. So, why are you phaffing about with 47% HBr when you can walk over to the local hardware shop and do something similar with 32% HCl? Eleusis contends that aq. 47% HBr can't be used to make bromosafrole under normal conditions. This is the original article that sparked it all off, where Carter describes the addition of HBr to Alkene. H. E. Carter, Metabolism of Amino Acids, J. Biol. Chem. 108, 1935, p 623. 200 gm. of glacial acetic acid containing 150 gm. of hydrogen bromide were placed in a 500 cc. bottle in an ice bath and 100 gm. of allyl benzene were added. A rubber stopper was wired in the bottle and it was allowed to come to room temperature slowly with occasional shaking. In 10 to 12 hours the original two layers merged into a clear red solution. After 24 hours the contents of the bottle were poured on crushed ice. The crude bromide was separated and the water layer extracted with petroleum ether. The two fractions were combined, washed with water and sodium carbonate, and dried over anhydrous sodium sulfate. The petroleum ether was distilled through a 20 cm. column and the residue was fractionated. The yield of crude bromide (90-95 per cent pure) was 235 gm. (92 per cent of the theoretical amount). Eleusis contends that Fester was talking through his arse when he described the prep. of bromo-safrole using this method. By implication, Eleusis implies that most of the rest of Fester's book is made up.
==================================================================== ========= From: [email protected] (Jon Taylor) Subject: Newest MDMA Synthesis Date: 18 Apr 1994 17:10:03 -0600 This is an MDMA sysnthesis I OCR's out of my copy of _Secrets of Methamphetamine Manufacture_, which will probably end up being the one that I put in the next revision of my MDMA FAQ. I thought I'd also post it as a separate file as well. -Jon CUT HERE /\/\/\/\/\/\/\/\/\/\/\/\ MDMA Synthesis: Bromosafrole method Scanned fom _Secrets of Mthamphetamine Maufacture_ A good alternative to the Ritter reaction is a two step procedure first reacting safrole with hydrobromic acid to give 3,4methylenedioxyphenyl-2-bromopropane, and then taking this material and reacting it with either ammonia or methylamine to yield MDA or MDMA respectively. This procedure has the advantages of not being at all sensitive to batch size, nor is it likely to "run away" and produce a tarry mess. It shares with the Ritter reaction the advantage of using cheap, simple, and easily available chemicals. The sole disadvantage of this method is the need to do the final reaction with ammonia or methylamine inside a sealed pipe. This is because the reaction must be done in the temperature range of 120140 C, and the only way to reach this temperature is to seal the reactants up inside of a bomb. This is not particularly dangerous, and is quite safe if some simple precautions are taken. The first stage of the conversion, the reaction with hydrobromic acid, is quite simple, and produces almost a 100% yield of the brominated product. See the Journal of Biological Chemistry, Volume 108 page 619. The author is H.E. Carter. Also see Chemical Abstracts 1961, column 14350. The following reaction takes place: [ Structural diagrams deleted]
To do the reaction, 200 ml of glacial acetic acid is poured into a champagne bottle nestled in ice. Once the acetic acid has cooled down, 300 grams (200 ml) of 48% hydrobromic acid is slowly added with swirling. Once this mixture has cooled down, 100 grarns of safrole is slowly added with swirling. Once the safrole is added, the cheap plastic stopper of the champagne bottle is wired back into place, and the mixture is slowly allowed to come to room temperature with occasional shaking. After about 12 hours the original two layers will merge into a clear red solution. In 24 hours, the reaction is done. The chemist carefully removes the stopper from the bottle, wearing eye protection. Some acid mist may escape from around the stopper. The reaction mixture is now poured onto about 500 grams of crushed ice in a 1000 or 2000 ml beaker. Once the ice has melted, the red layer of product is separated, and the water is extracted with about l00 ml of petroleum ether or regular ethyl ether. The ether extract is added to the product, and the combined product is washed first with water, and then with a solution of sodium carbonate in water. The purpose of these washings is to remove HBr from the product. One can be sure that all the acid is removed from the product when some fresh carbonate solution does not fizz in contact with the product. Once all the acid in the product is removed, the ether must be removed from it. This is important because if the ether were allowed to remain in it, too much pressure would be generated in the next stage inside of the bomb. Also, it would interfere with the formation of a solution between the product and methylamine or ammonia. It is not necessary to distill the product because with a yield of over 90%, the crude product is pure enough to feed into the next stage. To remove the ether from the product, the crude product is poured into a flask, and a vacuum is applied to it. This causes the ether to boil off. Some gentle heating with hot water is quite helpful to this process. The yield of crude product is in the neighborhood of 200 grams. With the bromo compound in hand, it is time to move onto the next step which gives MDA or MDMA. See Chemical Abstracts 1961, column 14350. Also see Journal of the American Chemical Society, Volume 68, page 1805 and Journal of the Chemistry Society, part 2 1938, page 2005. The bromo compound reacts with ammonia or methylamine to give MDA or MDMA: [ Sructural diagram deleted ]
To do the reaction, 50 grams of the bromo compound is poured into a beaker, and 200 ml of concentrated ammonium hydroxide (28% NH3) or 40% methylamine is added. Next, isopropyl alcohol is added with stirring until a nice smooth solution is formed. It is not good to add too much alcohol because a more dilute solution reacts slower. Now the mixture is poured into a pipe "bomb." This pipe should be made of stainless steel, and have fine threads on both ends. Stainless steel is preferred because the HBr given off in the reaction will rust regular steel. Both ends of the pipe are securely tightened down. The bottom may even be welded into place. Then the pipe is placed into cooking oil heated to around 130 C. This temperature is maintained for about 3 hours or so, then it is allowed to cool. Once the pipe is merely warm, it is cooled down some more in ice, and the cap unscrewed. The reaction mixture is poured into a distilling flask, the glassware rigged for simple distillation, and the isopropyl alcohol and excess ammonia or methylamine is distilled off. When this is done, the residue inside the flask is made acid with hydrochloric acid. If indicating pH paper is available, a pH of about 3 should be aimed for. This converts the MDA to the hydrochloride which is water soluble. Good strong shaking of the mixture ensures that this conversion is complete. The first stage of the purification is to recover unreacted bromo compound. To do this, 200 to 300 ml of ether is added. After some shaking, the ether layer is separated. It contains close to 20 grams of bromo compound which may be used again in later batches. Now the acid solution containing the MDA is made strongly basic with lye solution. The mixture is shaken for a few minutes to ensure that the MDA is converted to the free base. Upon sitting for a few minutes, the MDA floats on top of the water as a dark colored oily layer. This layer is separated and placed into a distilling flask. Next, the water layer is extracted with some toluene to get out the remaining MDA free base. The toluene is combined with the free base layer, and the toluene is distilled off. Then a vacuum is applied, and the mixture is fractionally distilled. A good aspirator with cold water will bring the MDA off at a temperature of 150 to 160 C. The free base should be clear to pale yellow, and give a yield of about 20 ml. This free base is made into the crystalline hydrochloride by dissolving it in ether and
bubbling dry HCl gas through it. ==================================================================== ========= Subject: From: Date:
Bromosafrole Prep from Uncle Fester Lasertek 1996/05/17
Members of the alt.drugs.chemistry discussion group: My many thanks for the opportunity to get on board and engage in a food fight with someone named Eluisis. As a token of my appreciation, I'm going to leave you with some of my original research on a couple of topics which may interest you. I think anyway it's original. If anyone comes up with references covering these topics, let me know. PREPARATION OF BROMOSAFROLE FROM 48% HYDROBROMIC ACID A greatly improved procedure using 48% HBr to make bromosafrole is my own invention, and it is with unbounded pride that I offer this advance to the field of MDA manufacture. This procedure is both quicker and much higher yielding than the procedure worked out by the jackass who wrote the article for the Alabama Academy of Science cited earlier. This so-called researcher was hired by the DEA to fool around with 48% HBr to see if it could be used to make MDA or MDMA from sassafras oil. They had busted someone with 48% HBr and a load of sassafras, and to make their case they needed to show that it could be done. The result is a testimonial to the power of money for it, some people will say anything. I just wonder who is rotting away in a cage as a result of his inflated claims. You bought this book for the straight poop, so let your Uncle be your guide. To get good yields of bromosafrole from 48% HBr and sassafras oil, mix one part sassafras oil with one part glacial acetic acid and two parts 48% HBr in a suitable-sized flask. Chill this mixture down in ice, then with strong
magnetic stirring pass a stream of dry HCl gas into the solution for about an hour. See Chapter 5 for the dry-HCI gas-generator. How much HCl to pass into solution? Well, for a batch using 50 ml of sassafras oil, the amount of dry HCl generated by dripping 75 to 100 ml of sulfuric acid onto a half-full 500 ml flask of salt-hydrochloric-acid paste is about right. A little bit more wouldn't hurt. Good ventilation is required! As the dry HCI passes into the solution, it dehydrates the 48% HBr, causing it to react with the safrole. The dehydration and the reaction both generate a good deal of heat, so fresh ice will periodically have to be put into the bath around the reaction flask. The temperature of the reaction shouldn't be allowed to rise above 10-15∞ C. The reaction mixture first turns green then blue, then purple, and finally burgundy. When the bubbling with dry HCl is finished, stopper the flask and continue stirring in the cold for two days. Sometime around a day into this stirring, no separation of phases can be seen when stirring ceases. The amount of dry HCl produced by dripping sulfuric acid onto salt will vary with the exact conditions, so the batch should be checked for reaction before quenching it on ice. It doesn't hurt to add too much dry HCl, within limits, but too little won't dehydrate the acid sufficiently. To check this, after the day of stirring is done, pour some of the reaction mixture into a beaker, then from beaker, return it to the reaction vessel. This leaves a coating of the reaction mixture on the glass in the beaker. Fill the beaker with water to rinse away the fuming acids, empty it, and sniff inside the beaker for the aroma of the organics clinging to the glass. If it still smells like the candyshop fragrance of sassafras oil, an additional bubbling with dry HCl is going to be required, followed by another day of stirring in the cold. After the first batch or two, it's easy to gauge how much dry HCl one is getting.
If the aroma has changed to something more chemical and fruity, yes just like phenylacetone, sufficient HCl has been added. When two days of stirring are completed, the batch is poured onto crushed ice as in the other methods. When the ice has melted, a little bit of toluene is added (a volume about equal to the amount of sassafras oil used), and the water-bromosafrole mixture shaken. Prior to adding toluene, the bromosafrole will likely be on the bottom of the container, but adding toluene and shaking, it should be floating on top. It's still burgundy-colored. Separate the bromosafrole layer with a sep funnel, and then wash it with about 3 volumes of water. Add bicarb slowly until the fizzing stops. This will knock out the carried-over HBr, HCI and acetic acid. Shake some more, then add a little more bicarb to make sure all the acid has be neutralized. Separate the toluene-bromosafrole, and place it in a distilling flask. Distill off the toluene at normal pressure, then vacuum-distill the remaining bromosafrole. A vacuum that distills safrole at 110∞C will distill bromosafrole at about 140-145∞ C. Some chlorosafrole distills at about 125∞C. It can be used as is, or the chlorosafrole can be converted to iodosafarole according to the directions found in the "Psychedelic Amphetamine" chapter in this book. The yield is about 66-75% conversion to bromosafrole, with the remainder being unconverted safrole and chlorosafrole. Bromosafrole smells a lot like phenylacetone. It may turn pink on standing, and should be stored in a freezer until used. With this posted, has anyone ever discussed the bad effects that the zinc galvanizing on steel pipes has on the next stage of the reaction with ammonia or methylamine? White crystals galore! It most be stripped off in dilute HCL prior to use. Along a similar line of thought, has the reaction of safrole with dry HCl in toluene been considered? Chlorosafrole has interested me for some
time. It too smells like phenylacetone. My experiments indicate that HCl adds poorly to safrole at slightly elevated temps. About 10% yield in a three week reaction time. Higher temps would be needed to bring about reaction, but below the about 100C temp where ether cleavage with HCl happens. Once one has chlorosafrole, what good is it? It can be converted to iodosafrole by refuxing with 2 moles of NaI in acetone, and then filtering out the NaCl precipitated, boiling off the acetone under vacuum, and recovering the iodosafrole by extraction with toluene. What good is iodosafrole? Compare to the 2 halogen propyl benzenes listed in JACS 68, pages 1009-11(1946). Similar chloro derivatives give small yields, whereas the bromo derivative of safrole gives a decent yield of product at lower temp. I see a trend here. The iodine is a better leaving group, and should give a superior yield at lower reaction temp. Read over all the relevant lit before proceedings Also know that a significant amount of mail I've recieved indicates that the presence of a significant (that means more than incidental) amount of water in the pipe bomb with bromosafrole yields excessive amounts of tar. Just adding 40% mehylamine or 28% NH3 to the alcohol is too much water. This is fine for making meth or benzedrine by this method, but for MDA some dehydration is called for. I hope this contribution to the discussion group causes serious exchange. I also hope you've enjoyed meeting my friend down the street LASERTEK. He's not a chemist, rather he works metal using a laser. He hasn't had so much fun since he discovered your group. Best, Fester ==================================================================== ========= Ritter
Yup, that's the procedure I've been touting for years now. I don't know how many times I have to say that Fester actually did something right this time! The only variation I've made on his procedure is to bubble in about half again as much HCl(g) as Fester calls for. Other than that the reaction procedes EXACTLY the way he quotes it, color changes and all! Just make sure the ice bath is kept chock full of ice for the entire duration of the rxn. ==================================================================== ========= From: [email protected] (Lamont Granquist) Newsgroups: alt.drugs Subject: Re: Newest MDMA Synthesis Date: 19 Apr 1994 20:31:00 GMT Message-ID: <[email protected]> [email protected] (Jon Taylor) writes: > This is an MDMA sysnthesis I OCR's out of my copy of _Secrets of >Methamphetamine Manufacture_, which will probably end up being the one >that I put in the next revision of my MDMA FAQ. I thought I'd also post >it as a separate file as well. According to J-Forensic-Sci 35(3):675-697 this isn't the best method of making methoxylated amphetamine derivatives. The author claims that yields are low, synthing the intermediate is time consuming (although so is synthing MD-P2P), and potentially hazardous -- I don't know why its hazardous, but the author references ANALOG 9(3):1-10 which is an article by Hansson, R.C. entitled "Clandestine Laboratories Production of MDMA." It is suggested that the synths using cyanoborohydride, aluminum amalgam, borohydride or Raney Ni catalysis from MD-P2P would be more likely to be used. The two former ones are preferred as the borohydride method has a lower yield and the catalysis requires the construction or purchase of a hydrogenation unit. ====================================================================
========= Subject: Iodosafrole Secrets: the DMSO Method Date: 1997/05/08 The iodosafrole method of producing MDMA and MDA is indeed viable; being one of those multikilagram processes here in the Netherlands someone was asking about. The key is using the DMSO method of producing anhydrous HI. NaI is dissolved in DMSO and then an equimolar amount of H2SO4 is added. Na2SO4 precips out. The reason the process works is that DMSO has the peculiar property of dissolving lots of NaI. (the solubility is much higher for NaI than for NaBr, making the HI process much better for large qty- make note of this you crank manufacturers) (will phoshorus and iodine be obsoleted?? :) And DMSO makes such acids particularly active. And HI is not likely to cleave ether substituted allyl benzenes like apiole, asarone, and myristicin. (See Feiser and Feiser in Reagents for Organic Synthesis vol. 1 for details) Extraction of iodosafrole left to your own imagination. secret!!
Our trade
Finally, amination is done at room temp with methylamine for MDMA or with hexamine (via Delepine process) to get MDA or other analog. Happy trails!
Pugsley and Wednesday.
==================================================================== ========= From: [email protected] (Anonymous) Subject: Pugsley: on Bromosafrole via DMSO Method/ Various topics, advice Date: 1997/08/31 Congratulations to the poster on getting the DMSO method of bromosafrole synthesis to work. Its incredibly easy- but too easy for anyone to believe it works. Its the amination thats the more difficult part. Be careful
if you decide to make your own methylamine via the formaldehyde/NH4Cl method- it gives off alot of methyl formate at the start, which is really nasty stuff, almost as bad as dimethyl sufate. It turns into formic acid in your lungs. Big Mr. Yukk sticker on that one. Another chemical given off, formylal, has a nice smell and is relatively safe, but masks the danger involved. I'm still interested in hearing in this NG from anyone doing the Delepine reaction with hexamine camping fuel to get MDA. Bromosafrole has given mixed results. Iodosafrole works at room temp. I don't see too much problem with getting NaI, since it can be diverted from table salt and photographic applications. I don't know if CRSB sells it, but they should. (if they stay in business) I don't think that meth labs use it, since in aquious media, H2SO4 turns it into elemental Iodine plus whatever salt of Na. DMSO doesn't suffer from that problem. I still see a lot of synthesis and talk on methcathinone. Very little said about cyclization products, which is one of a couple reasons some people can't seem to make it. There were some posts here a while ago referencing the specific papers on the subject. I didn't have to time to go to the library and dig all that stuff up. Never keep academic papers or chemistry books of any kind on your property if you are making "stuff". Memorize, memorize, memorize. Try to use anything but commercial glassware if you can. A suprising amount of chemistry can be done with spagetti sauce jars and various types of tubing. Even holes can be drilled in spagetti sauce lids and brass pipe fittings soldered, for various operations involving gases. For exampe, I performed the entire asarone and anethole pseudonitrosite syntheses for TMA and PMA respectively, using nothing other than sauce jars and a large pyrex juice dispensers as containers. One sauce jar has
two fittings attached to it so that an outlet tube for the N2O3 could be attached, plus an inlet for air from a fish tank bubbler. The pyrex juice dispenser was used to contain the etherial solution of essential oil. (By the way, PMA or 4-MA as Schulgin calls it, is quite the rollercoaster ride. Except you start out at the top of a gigantic hill, instead of gradually making your way to the top. And it hits real suddenly.) I think a DA would really think twice about going after someone who had no paper evidence of drug chemistry efforts, and just a bunch of old jars lying around. If you ever read accounts of DEA busts, they always tell about all the drug and bomb making Loompanics books they find. If all they find are Nancy Drew mystery novels, they'd look pretty silly. Various people have been asking about where they can buy essential oils. There are a number of web site based mail order suppliers. Just type "essential oil" into AltaVista. For example 16oz of anise oil costs $12. Same price for sassafrass. Calamus oil costs anywhere from $60-200 for 16oz depending on where you buy it. Make certian to get the Indian oil. The others have no asarone in them. Nutmeg and elemi oil are reasonable also. Parsley seed oil has gone up to about $100/16oz. If you isomerize it to isoapiole, it makes way cool DMMDA. Well, thats all the comment I can think of for now. I really haven't been doing much in quite number of months. I get burnt out on making drugs and find new interests. I've never had any desire to make money that way. After all, anyone smart enough to make their own druggs can probably make alot of money legit. Its always been a curiosity thing. I am eagerly awaiting Fester's "Advanced Meth Chemistry Book". That should be interesting. Wednesday sends her good wishes. Best Regards,
Pugsley ==================================================================== ========= From: [email protected] (Josh R Hardin) Subject: Pugsley & Wednesday Please Read Date: 1997/09/07 First, let me thank you for the excellent information about the DMSO-Bromosafrole method. For those of you unfamiliar with it, I strongly suggest searching dejanews. Basically, it uses DMSO, NaBr (from darkroom supply houses), and H2SO4 (drain cleaner) to synthesize anhydrous HBr which converts Sassafras oil to Bromosafrole. This method is better than using commercially available HBr. The authors suggest that after obtaining Bromosafrole, a 5g tablet of Hexamine camping fuel can be added to start the Delepine reaction to convert it to MDA. Does anyone have any references for the Delepine reaction? Is the mixture refluxed, cooked in a pipe bomb, or allowed to sit for a period of time? Does anyone have any numbers? The other method of converting bromosafrole to MDA via ammonia and isopropyl alcohol or ammonia hydroxide gives poor yields (20%) and doesn't smell too good to the neighbors. In another post, Pugsley discusses iodosafrole. This method uses DMSO, NaI, and H2SO4 to yield anhydrous HI. NaI is easily diverted from salt licks. I believe that the recipe is 100ml chilled DMSO + 7.8ml H2SO4 + 43g NaI. Although this can be used for making speed without having to purchase red phos or iodine, can it be used for MDA? If one were to use the HI to convert sassafras oil to Iodosafrole, could it be converted to MDA via the Delepine reaction? How? Let's use the example of 5ml Sassafras oil + 100ml DMSO + 7.8ml H2SO4 + 43g NaI. After it has reacted for a day or so, there should be iodosafrole - right? Now, would adding a 5g Hexamine camping fuel tablet start the delepine reaction? What are the times and methods - reflux, bomb, let sit? How do the yields compare to the bromosafrole methods?
Finally, in their amazing post about pseudonitrosites, the authors state that the method can be used on various propenyl benzenes. This would allow isosafrole to be easily converted to MDA. Howver, in Fester's Practical LSD Manufacture, he states that it will work on all propenyl benzenes EXCEPT isosafrole. Howver, the two procedures are different. Will it work? What is DMMDA like? Thanks for the help. BTW, please do not respond to this e-mail account. I can be reached at:
It is not mine.
[email protected] Thanks, HI Guy ==================================================================== ========= From: Secret Squirrel Subject: COME MOCK MY DMSO FAILURE Date: 1997/06/03 Let me first apologize for the outburst. After investing so much time and energy into the project, to have it fail miserably at the end was frustrating, to say the least. I greatly appreciate Pugsley's and Wednesday's contributions to poor chem trench grunts everywhere. That said, prepare the mudslings for my crappy technique. Keep in mind none of this actually happened and the entire post is pure fiction :). The DMSO was purchased anhydrous at the local homeopathy shack (it even says "for use as solvent only" *grin*). It would freeze solid when put in the fridge (a good sign). Kodak anh. KBr (from darkroom supply) was used in place of NaBr, molar scaled up of course. Sassafrass oil was used straight to take advantage of eugenol, etc. I was unable to locate ocotea cymbarum locally. The relative quality of the essential oil I have no idea nor reference for, all that can be said is that it was expensive. 175ml DMSO was chilled(frozen) in an acetone-rinsed 500ml round-
bottom and the flask placed in an ice-water bath. There was then added 30.6g H2S04 drain cleaner with some evolution of heat. The drain cleaner was slightly discolored brown even though it came from a sealed container (although the container is probably a year old). Looking at the container now, the acid is dark brown-red with chunks, disgusting; evidently I had drawn off the undisturbed clearer top part when doing this, but still undoubtedly introduced impurities. I hadn't realized it at the time, or even much later. 69.3g KBr was then added. The initial granules falling into the flask produced a fine mist, much like ammonium chloride forming above a bottle of muriatic and a bottle of ammonia placed next to each other, which shot up a bit and gave me a bit of a gag. Perhaps the addition order should be reversed. The soln turned orange, and began to stink. The stench is a lot like garlic, and exactly like the smell of the sweaty guy who had the locker next to mine in high-school gym class (ugh). A lot of KBr remained undissolved despite repeated stirring with a glass rod, as expected. 10ml sassafras oil was pipetted in. The stink changed from garlic/ sweat to garlic/sweat/bandaids. The soln turned brownish-red with a sort of mobile greenish band on top. The flask was tightly stoppered, then entirely enclosed in a ziplock bag, which still didn't keep in all the smell, and left on a dark shelf at room temp for 2 days with occasional swishing and/or stirring. It turned entirely brownishred. The solids remained on the bottom throughout, being broken up upon stirring. My notes are missing for the next part, but around 600 ml of distilled water was added in two portions, the entire thing getting dumped into a liquor bottle. A dark red, clear oil settled to the bottom; the aqeuous layer turned cloudy tan as the solids dissolved into it. The aq layer
was poured off, and the oil washed with a bit more H2O. oil was (guessing) maybe 7 or 8 ml.
Yield of
To the oil was added 400ml denatured alcohol and 10.2g crushed camping fuel, which was used straight but was nice and white crystalline. A few small pieces of fuel didn't dissolve right away, but had after the soln sat one day. The soln was left alone until the 3rd day, when heating was attempted, but aborted due to pesky interlopers. The 4th day the soln was finally refluxed on steam bath for about 6 hrs. It sat one more day (good undisturbed lab space is hard to come by). The soln remained a reddish tea color. 50ml muriatic driveway cleaner (31.45% HCl) was then added in increments. The first 20ml produced loads of fine white needle crystals, filling the 500ml flask halfway and nearly giving me a heart attack for the few seconds until my brain realized there were just too many and they were probably ammonium chloride and unreacted hexamine. As the rest of the HCl was added, the crystals all dissolved, but then gradually a white ppt formed, snowy and unlike the needles. The flask was refluxed on steam bath about 4 hrs and then sat for a day. The ppt did not dissolve with heat. 125ml H2O was added, which dissolved the ppt and turned the soln opaque tan. A dark clear red oil settled out (I assumed it to be unreacted bromosaf). The pH at this point was less than 3, determined by indicator paper. The oil was seperated and the aq soln extracted with 3x20ml 1,1,1-TCE. The TCE extracts were combined w/ the oil and set aside. 80ml 25% NaOH (lye) in water was added to make the aq soln strongly basic. After shaking, a (small amount of) red-brown oil settles to the bottom. The oil was sep'd and the aq layer extracted with 3x20ml 1,1,1-TCE. The TCE extracts were orange-ish. The remaining aq soln looks like iced tea. Post-mortem dissection of my notes reveals the combined TCE extracts and oil did not get an additional water wash. The TCE was distilled off in a
flask I finally remembered to tare beforehand, leaving 7.4g of a dark black-red oily goo, which was dissolved in 12.5ml anh. isopropanol and treated with a couple ml of HCl, then evaporated on steam (ala ZWITTERION, remember him?) to give a disgusting orange tar (which had to be scraped off with acetone), a few grains of probably NaCl, and a whole lotta stink. I would guess the stink was from methylamine HCl (from unreacted hexamine hydrolyzed during the second part of the Delepine) subliming with the heat; it smelled kind of like burning plastic. A cold beer was then searched for, to no avail, at which point a mentally and physically exhausted fetal position was assumed, with soft crying. For my next attempt, I'm considering (among other things) doing the first part of the Delepine in TCE instead of alcohol, which would allow me to see the progress of the rxn, harvesting the pptd hexamine salt and returning the rest to the heat. The salt could then be hydrolyzed in a separate reaction. I'm also considering use of the bomb. ==================================================================== ========= Date: Fri, 19 Sep 1997 17:37:07 -0600 From: [email protected] Subject: The Real Info - Please Read HI can be made by reacting phosphoric acid (it can be purchased at HOME DEPOT in the bldg supply section) and NaI or KI. NaI can be found at salt licks. HI can also be made by reacting dilute sulfuric (it's not spelled with a ph bookworm) with NaI or KI. Now this produces HI gas. So, using a variation of Tom Kasper's push pull bullshit, in jug have 5L of phosphoric acid connected by neoprene automotive feul tubing to a champagne bottle containing NaI, Ephedrine or pseudoephedrine, and H2O. Supposedly HI gas bubbled through a solution of 1 part ephedrine to 2 or 3 parts water under
25 psi will make meth without the need for red phos. The best quench for the Birch is ammonium chloride. the gas through some HCl.
Bubble some of
There was a post by bookworm in which he said that there was a "recipe" that used 75:15:10 ratio in which 75g of NaI or KI:15g TripleSuperPhophate (might be tri-sodium phosphate):10g Al. If it works, which I doubt, the 10g of Al should be AlCl because it is hygroscopic. This is all in one jug which is connected to another jug containing phophoric acid. He claims that the temp should be under 80C - bullshit - and should take 2-4 days bullshit. Follow the 3 hour push/pull by that anon guy in Santa Barbara. ==================================================================== ========= Subject: From: Date:
Re: HBr + Safrole = ?????? [email protected] (Eleusis) 1995/10/15
In article <[email protected]>, [email protected] wrote: > So Fester is a Puss Face? Is the HBr route to MDA a total waist of time? > The reaction appears feasable on paper. Does it work at all? Or are the > yeilds just pathetic? What modifications would one need to make to this > reaction in order to successfully synth. MDA? Any good HBr synth > directions??? Any good alternatives? And Reload old articles, starting about 2 months ago. This has been thoroughly hashed over. In fact, I just posted a synopsis answer to this question about a week ago. Surely that article is still on most servers. Anyway, if I *were* to do it, I would consult the original H.E. Carter article, where I would find the following corrections to Fester's questionable chemistry deviations: 1) Anhydrous HBr gas is dissolved in glacial acetic acid, not Hydrobromic Acid, and definitely not the azeotropic acid.
2) 100g of allylbenzene was used in Carter's, 100g of safrole is specified by Fester, but allylbenzene has a mol. weight of 118, while safrole is 162. That means that Carter was brominating .85 moles, while Fester is attempting to brominate 0.62. Fester didn't even bother converting molar quantities! Etc... Otherwise, the process seems facile. ==================================================================== ========= Subject: From: Date:
Re: MDA from MDP2P [email protected] (Eleusis) 1995/11/01
Bromination of Safrole at the secondary carbon of the double bond proceeds at less than 5% yield if 48% HBr is substituted for 66% under pressure, at which point yields are closer to 85% (J.Bio.Sci. v108). This is a "minor detail" that changes yield by 80 percentage points. ==================================================================== ========= Posted by ChemHack on the Hive Chemical Abstracts 1961, column 14350, paragraph e (S.Biniecki & E.Krajewski) - Safrole + 70% HBr at 0C for 12hours produced 97% yield of bromosafrole. Same source paragraph f - 4.7g bromosafrole + MeNH2 in alcohol heated 3 hours at 130C, clean-up and treatment with HCl yields 1.4g MDMA and 1.9g unchanged bromosafrole recovered. Journal of the Chemistry Society, part 2 1938, page 2008, 4th complete paragraph titled Addition of Hydrogen Bromide to Safrole (K.H.Lin & R.Robinson) - Safrole in solution of perbenzoic acid in benzene was saturated with hydrogen bromide. On each of next 7 days 1ml of perbenzoic acid solution added. [CH: to keep it in solution?] The mixture shaken and kept for 17 days. Water washed, treated with sodium carbonate, washed again, dried, and distilled giving unspecified yield of colourless
mobile liquid identified as safrole hydrobromide. Journal of the American Chemical Society, Vol 68, page 1806, Sept. 1946, 3rd complete paragraph (B.Riegel & H.Wittcoff) - Hydrogen Bromide gas bubbled into solution of glacial acetic acid and allylbenzene led to formation of 2 layers which were dispelled by adding more acid. Rxn kept cold overnight, poured into icewater yielding heavy bromide taken up in EtOH, aqueous layer extracted and extracts pooled. Washed with dilute bicarb then with water then dried over sodium sulfate then distilled to yield 71% colorless B-Bromopropylbenzene. Journal of Biological Chemistry, Vol 108, page 623, 1934/5?, first complete paragraph (H.E.Carter) - 200g glacial acetic acid containing 150g hydrogen bromide in bottle in ice bath. 100g allylbenzene added, stoppered, and allowed to come to room temp slowly with occasional shaking. Two layers merged into clear red solution after 10 to 12 hours. After 24hours contents poured onto crushed ice, bromide separated, water extracted with pet ether. Extracts pooled, washed with water and sodium carbonate, dried over sodium sulfate. Distilled bromide was 90-95% pure and total yield was 92% of theoretical. ==================================================================== ========= From:
The Journal of the Chemistry Society, part 2 1938
page 2005.
379. Experiments on the Synthesis of Substances related to the Sterols. Part XXV. by K. H. Lin and Robert Robinson. This article refers to the bromosafrole as Beta-Bromodihydrosafrole. [discussion of related compounds deleted] Addition of Hydrogen Bromide to Safrole.--Only one of the many experiments made is here described. A mixture of freshly distilled safrole (8.1 g.), a solution of perbenzoic acid in benzene (2 cc of 0.3N), and benzene
(100 cc) was saturated with hydrogen bromide (2 hours). On each of the next 7 days perbenzoic acid solution (1 cc) was added, and the mixture shaken and kept for 17 days. The mixture was then washed with water, dilute aqueous sodium carbonate, and again water and the benzene layer was separated, dried, and distilled. The fraction (6.5 g), b.p. 145.5-153C at 9.5mm, was a colourless, mobile liquid and was identified as the known safrole hydrobromide; Robinson and Zaki (J., 1927, 2489) give b.p. 160C at 16mm. The addition of hydrogen bromide to safrole was also carried out (a) in the presence of alpha-heptenylheptaldehyde, and (B) in the presence of anhydrous ferric cloride. The same beta-bromdihydrosafrole was obtained in both cases. ==================================================================== ========= This procedure calls for reactions under high pressure, this is potentially very dangerous. See ANALOG, Vol 9, No. 3, Nov 1987, pp. 1-10, by R.C. Hansson for additional dangers. Do not try this at home. From:
Chemical Abstracts 1961, column 14350.
Preparation of DL-1-(3,4-methylenedioxyphenyl)-2(methylamino)propane and DL-1-(3,4-dimethoxyphenyl)-2-(methylamino)propane. Biniecki and Edmund Krajewski.
Stanislaw
Safrole (5.3 g.) added dropwise at 0C to 21 g. 70% HBr, the mixt. left 14hrs. at 0C, poured on ice, extd. with Et20, and the ext. distd. in vacuo yielded 97% 3,4-CH202C6H3CH2CHBrMe (I), n D-24 1.5634. [Analogously, 5.73g. 4-allylveratrole with 18.6 g. 70% HBr gave 81% 3,4(MeO)2C6H3CH2CHBrMe (II), n D-18 1.5605.] (I) (4.7 g.) with 26 g. 18.2% alc. MeNH2 heated 3 hrs. at 130C, the solvent and excess amine distd., the residue acidified with HCl to Congo red, extd.
with 30 ml. Et2O to remove unchanged (I), the aq. layer treated with 10 g. K2CO3, extd. with Et20, and the exts. distd. gave 1.4 g. 3,4-CH202C6H3CH2CHMeNHMe, n D-19 1.5311, after 1.9g. (I) was recovered; hydrochloride m. 148-149C. [Similarly, 7.2g. (II) and 22.5 g. MeNH2 after 10 hrs. at 140C and similar working up (NaOH used instead of K2CO3 and CHCl3 substitued for Et2O in the last extn.) gave 2.35 g. 3,4-(MeO)2C6H3CH2CHMeNHMe, n D-22 1.5265; prepn. of the hydrocloride, m. 114-119C, was not successful unless the base was purified via the perchlorate, m. 180-181C.] ==================================================================== ========= From: The Journal of the American Chemical Society, volume 68, page 1805 PYRIDINIUM ANALOGS OF THE PRESSOR AMINES. by Byron Riegel and Harold Wittcoff
I.
THE BENZENE SERIES
[discussion of other compounds deleted] Beta-Bromopropylbenzene.--Although this compound had been prepared previously by Carter by the addition of aqueous hydrobromic acid to allylbenzene, it was decided to employ an alternative procedure. The induction of a rapid stream of hydrogen bromide into a solution of 10g. of allylbenzene in 25 ml. of glacial acetic acid over a period of two hours led to the formation of two layers which were subsequently dispelled by the addition of 20 ml. more of solvent. The reaction mixture, having been subjected to low temperatures overnight, was poured into ice water to yield a heavy bromide which was taken up in ether and combined with the solution which resulted from the ether and benzene extraction of the aqueous layer. The solution, having been washed with dilute bicarbonate and with water, was dried over sodium sulfate. Thereupon, the solvent was evaporated to obtain a reddish oil which on fractionation yielded 12g.(71%) of a colorless liquid which distilled at 77-80C at 1mm. ==================================================================== =========
Chlorosafrole JOC 45, 3527-3529 (1980) 16.2 grams (0.1 mole) of safrole was added to a mixture of 50 ml 37% HCl (0.5 mole) and 4.0 grams (0.01 mole) of trioctylmethylammonium chloride (Aliquat 336), and the two-phase mixture was heated at 115∞C (bath temp) with magnetic stirring for two hours. The solution was extracted with 1x20ml and 2x10ml CH2Cl2, and the pooled extracts was freed from solvent by evaporation. The dark residue was distilled under aspirator vacuum which gave two fractions: 113-135∞C - 10.1 grams - Clear, safrole + chlorosafrole 135-165∞C - 4.8 grams - Cloudy, chlorosafrole + something. Chlorosafrole II 16.2 grams (0.1 mole) of safrole was added to a mixture of 150 ml 37% HCl (1.5 mole) and 4.0 grams (0.01 mole) of trioctylmethylammonium chloride (Aliquat 336), and the two-phase mixture was refluxed slowly for 5 hours. The solution was left to cool, and it was extracted with 3x15 ml DCM. The pooled organic extracts was washed with a little dilute Na2CO3, dried over MgSO4, and the solvent removed by evaporation. The black residue was vacuum distilled at 3 mmHg to yield 10.2 grams of clear 2chlorosafrole at 130-150∞C. There was also quite a lot of deep red residue in the distillation flask, probably consisting of the PTC and various polymerization products. Using the first procedure, but with 0.5 moles 48% HBr only produced tar. ==================================================================== ========= US Pat 3,864,115 Preparation of Bromosafrole 65 grams of safrole was dissolved in 100 ml of glacial acetic acid. At 20∞C,
there was added, with stirring, a solution of 100g HBr in glacial acetic acid. Stirring was continued for a further 12 hours at room temperature and the acetic acid was distilled off under vacuum. The residue was taken up in 200 ml of benzene and washing was effected several times with, in each case 100 ml of water. The benzene solution was dried over sodium sulfate. When fractionation was effected, 43 grams of bromosafrole of the bp 90∞C at 0.05 mmHg was obtained. This is the corresponding U.S. patent of the original German patent. ==================================================================== ========= Psychokitty: JOC 1980, 45, pp3529-3531 "Addition of Hydrohalogenic Acids to Alkenes in Aqueous-Organic, Two-Phase Systems in the Presence of Catalytic Amounts of Onium Salts." The PTC used in this reaction can be replaced with tetraoctylammonium bromide or the much cheaper are more easily obtained trioctylmethylammonium chloride (Aliquat 336). Other PTCs such as tetrabutylammonium bromide and triethylbenzylammonium chloride serve as very poor PTC catalysts due to their appreciable solubility in water. Also, any hydrohalogenic acid solution (HCl, HBr, HI) can be used. Don't know about HF though. A mixture of 16.8g of 1-dodecene (0.1 mol) (Note 1), 55.5mL of 48% hydrobromic acid (0.5 mol), and 5.1g of hexadecyltributylphosphonium bromide (0.01) is heated at 115degC (bath temperature) with magnetic stirring for 2hr (Note 2). The organic layer is separated (Note 3), the aqueous phase was extracted with dichloromethane (Note 4), and the solvent is evaporated. The resulting oil is distilled to give 21.4 of pure 2-bromododecane (Note 5). By treatment of the distillation residue with petroleum ether 4.8g (94.0%) of phosphonium bromide is recovered, which can be reused without
further purification (Note 6). Note 1: Don't be silly. Of course I didn't use 1-dodecene. Note 2: An attempt was made to carry out the reaction in a sealed round-bottomed flask surrounded by an oil bath with the temperature monitored by a thermometor immersed in the two-phase mixture held in place by a stopper. After about thirty minutes, pressure within the vessel increased and the stopper was blown off the top of the flask. Thermometor was recovered unbroken. The set-up was quickly modified through the addition of a reflux condensor with the thermometer relocated to the oil bath to monitor reaction temperature. No problems were experienced again and the process continued smoothly. The reaction mixture was then stirred for 4 hrs at the required temperature. Although there had been some gas evolution before, no reflux of the standard kind was observed. The 4 hour reaction was unintended (I lost track of the time). As the reaction progressed, the substrate darkened in color and became considerably more voluminous. A quick sniff from the top of the reflux condensor indicated a very significant change in odor. Smell was consistent with other published reports. At the completion of the reaction, the stirring was stopped, and the flask was removed to cool down. Note 3: Separation was not too difficult. Note 4: Solvent was added (toluene) as was dH2O and the phases separated cleanly. The solvent layer was then washed with saturated solution of sodium carbonate. The evolved carbon dioxide made separation somewhat difficult making basification with NaOH probably more desirable. Approximately one hour was needed for the separation of phases. The solvent layer was bluishblack. The water layer was slightly cloudy. Separation of the organic layer was commenced followed by two dH2O washes. Solvent was evaporated to yield a markedly viscous black oil that seemed to have a tarry appearance. Smell was pleasant and NOTHING
like the starting alkene. Assumed the reaction to be successful as there was a quantitative change with no apparant cleavage of the ether ring. Had there been any ring cleavage, the sodium catecholate would have formed during the basic washes and been carried away in the subsequent water washes. But then again, sodium carbonate and bicarbonate solutions when mixed with phenol inhibite the formation of sodium phenolate. This suggests that the sodium catecholate formation may have been retarded due to the sodium carbonate in solution. In any case, however, the presence of such a large amount of end-product substantiantes the assumption that the reaction did indeed effect some kind of change in the 1-alkene structure. Note 5: Distillation was attemted but due to an undetected leak in the vacuum system, the process ended in failure. Heat was applied in everincreasing amounts with the assumption that the 2-bromoalkane must necessarily have a very high bp. When the attempt was finally abandoned, it was too late. There was nothing left in the distilling flask except carbonized material and tar. Only DCM was able to remove it after letting it soak for a day. About 1/4 ml of oil distilled over into the receiving flask. It was deep red, and had a pleasant smell to it and was assumed to be the 2-bromoalkane. Being useless in such an amount, it was discarded. Note 6: Since all the product carbonized, this step was omitted. Another attemt was made. Conditions were identical except the reaction time was 30 min. This modification was made due to the information found in the article regarding the more facile and quick brominations of styrenes when compared to typical aliphatic alkenes. End product was less viscous and not as dark. Not as voluminous either. Significant odor of starting alkene was detected. Made the assumption that in order to be successful, reaction time must be in the order of two to four hours.
An attempt at substitution of the bromide atom for that of an azide was made. Two phase aqueous azide solution and 2-bromoalkene were reacted together in a manner identical to that of a published proceedure (I'll get the article for you guys soon). Even when using a very powerful stirrer, mixing of the two phases was virtually impossible due to the viscosity of the unpurified undistilled 2-bromoalkane. At the end of the reaction, an attempt was made to try reducing the azide product (it was assumed that there probably was no 2-azidoalkane formed due to the crappy lab technique applied to the previous step, but oh, well, what the hell.) Proper proportions of the suspected 2-azidoalkane MeOH and Ca metal were reacted the manner detailed in TSI and II. There was the fear that the PTC (hexadecyltributylphosphonium bromide) still dissolved in the suspected 2-azidoalkane would somehow undesirably react with the Ca metal, thus redarding the scheme of the reaction. Fears were abated as just a little bubbling occurred. In fact, practically nothing happened. The reaction was assumed to be a failure. Money was scarce, as was the need to have a working method. The 1-alkene to 2-bromoalkane to 2-azidoalkane to the final 2-amine route was abandoned as there was no detailed established proceedure to follow printed anywhere in the literature. The process was immediately substituted with the 1-alkene to 2-ketone to 2-amine strategy. Have had no regrets whatsoever. An attemt was once made to synthesize the 2-amine via the 2bromoalkane a long time ago using the proceedure published in Journal of Chromatographic Science Vol. 29, April 1991 pp.168-173 and Vol. 29, June 1991, pp.267-271. Although the 2-bromoalkane seemed to be (just seemed to be, mind you) produced in about 50% yield, the amine did not form. The process was deemed to suck bigtime, and of course, was abandoned. Here are some promising references describing newer and better ways
to effect 2-bromoalkane formation from 1-alkenes using hydrohalogens themselves or in their place, hydrohalogen precursors, reacted over silica or alumina. Here are the references: JACS 1990, 112, pp.7434-7436; ibid. 1993, 115, pp.3071-3079 JOC 1988, 53, pp.4477-4482. ==================================================================== ========= Equarius: 1) Aq. 48% HBr: 340g of H2SO4 (drain cleaner est.93%) are added to 1483g of 35% aq. NaBr solution (spa shock or something). The solution is distilled at atmospheric. ~425mls cums (all) over at 104:124 and is discarded. Then ~600mls of 48%HBr comes over as the 125:128.5 fraction. 2) HBr in GAA: 440g of 48%Hbr is placed in a flask and setup for gassing. Over (not in) the end of the gas bubbling tube is placed a single section of glass wool (nod to Piglet) which is held in place by tethlon tape. Add a pile of NaCl just so in peaks on the surface. H2SO4 is slowly dripped in over many hours and the gaseous HBr channeled into 253g of slightly chilled GAA. The solution is a nice orange color. Then GAA is weighed again and %age calculated. 28% (w/w) in this case. 3) BromoSafrole: 352g of 28%GAA is placed in a quart jar sitting in a cold water bath. 91g of Safrole (single distilled) are added in 4 portions over ~1 hour. Note: recycled Safrole from wacker / halogenation are not appropriate as isoS will not convert. Jar covered and stirred for 2d 19h (way overkill). Color progression is dark orange to green to deep bright red. The solution is dumped into ~450g of crushed dIce/dH2O in a sep funnel. Heavy BromoS goes to bottom and is seperated. The remainder is extracted with 86mls of pet ether and added to the BromoS. The solution should (but wasn't) be washed with a couple portions of dilute NaBiCarb
solution and best sit overnight with the BiCarb where substantle crap goes into the BiCarb water (thank gyro). The pet ether is distilled off. The remainder is distilled under vac (~~~28", big 3.9amp fridge pump). 11g of (iso)Safrole are collected from the 130:177 fraction. 64g of BromoSafrole are collected from the tight 178:181 fraction. Safrole normally comes over at ~140 with same pump. Suddenly black polymerized crap comes shooting through the condenser plugging up the entire apparatus which is exactly why crude solution must be washed with NaBiCarb. ==================================================================== ========= Chem Guy: From "Analysis of 1-(3-methoxy-4,5-methylenedioxyphenyl)-2propanamine (MMDA) Derivatives Synthesized from Nutmeg Oil and 3-methoxy-4,5Methylenedioxybenzaldhyde" It is in The Journal of Chromatgraphic Science, Vol. 34, Januuary 1996. The Nutmeg oil is a methanol extract. (Quotation) "BROMINATION REACTIONS A suspension of nutmeg oil in 48% HBr was stirred vigorously at room tempature for 7 days. The reaction was then quenched with the addition of crushed ice and extracted with ether. The ether extracts were combined, washed with water, and evaporated to dryness under reduced presure , and the resultant product oil was analyzed directly by GCMS. AMINATION REACTIONS The crude bromination product was disolved in methanol containing methylamine and stirred for several days. The reaction mixture was evaporated to dryness, and the resultant oil was disolved in 10% HCl. The aqueous acid solution was washed with ether and then made basic (pH 12) by the addition of NaOH pellets. The aqueous base solution was extracted with ether, then the combined ether extracts were evaporated to dryness under reduced pressure. The resulting oil was analyzed
directly. " In another arctile concerning this same topic except the oil was safrole. (Journal of Chromatographic Science, Vol. 29, april 1991, page 169) It says "... analysis showed the bromination occured slowly and required approximately 7 days to consume most of the Safrole.... The results of the present study clearly shows that MDMA and related designer drugs analogues of MDA can be prepared by amine displacement of bromosafrole obtained via bromination of the organic steam distillate of the roots of the sassafrs plant." That same article gives the same reaction method: "Bromination Reactions. Samples of sassafras oil or alkenes (5.0 g of safrole, isosafrole, eugenol, isoeugenol, etc.) in 48% HBr (25 mL) were stirred at room tempature for 7 days. The reactions were then quenched with the addition of crushed ice (25 mL) and extracted with ether (2 x 50 mL). The ether extracts were evaporated to dryness under reduced pressure and the resultant product oils analyzed directly. Amination Reactions. The crude bromination products (2.0 g) were dissolved in methanol (100 mL) containing 40% aqueous methylamine (20 mL) and stirred at room tempature for 4 days. The reaction mixture was evaporated to dryness and the resultant oil dissolved in 10% HCl (50 mL). The aqueous acidic solution was waqshed with ether (2 x 50 mL) and then made basic (pH 12) by the addition of NaOH pellets. The aqueous base solution was extracted with ether (2 x 50 mL) and the comgined ether extracts evaporated to dryness under reduced pressure. The resultant oil was analyzed directly." NOTE: This reaction can also use ammonia instead. ================================= I found two references to benzyl ether groups in my texts. The both say the benzyl ethers are "split by strong hydrohalogenic acids", AKA, --> HX, where X is I, Br, or Cl. But it doesn't say how easily, and one refernece says "... especially HI" (as we already knew) and it shows the equation: "ArOR + HI, concentrated, heat --> ArOH + RI" Now my question is, how concentrated do HBr and HCl have to be and
how much heat is required for this? It seems that room tempature may not be a lower limit for this method but a upper limit of tempature. Maybe if you did this at 0C for longer than 7 days you wouldn't have all this trouble? Next,... Found this in Journal of Organic Chemistry, 1980, Vol 45, 3527-3530. "Addition of hydrohalogenic acids to alkenes in aqueuos-Organic, two phase systems in the presence of catalyitic amounts of onium salts In previous works we reported that lipophillic quarternary ammonium and phosphonium salts show a high catalyitic activity in reactions promoted by hydrohalogenic acids in aqueuos-Organic two phase systems such as the conversion of alcohols to the corresponding halides and the cleavage of ethers. Recently quartenary ammonium salts were shown to extract hydrohalogenic acids from their aqueuos solutions into low polarity organic solvents." The article goes on to state the effecivness of the PTC's But it also states that this can cleave ether groups as well. reference given to this is "Synthesis, 1978, page 771". I had time to look this up but I'm sure it will clear some shit
for this. The haven't up.
================================ From Synthesis, 1978, page 771,... Cleavage of dialkyl and aryl alkyl ethers with hydrobromic acid in the presence of Phase]Transfer catalysts "Standard methods to hydrolyse ethers require particularly drastic conditions, e.g. the use of concentrated hydroiodic acid, or a large excess of concentrated hydrobromic acid in acetic acid or acetic anhydride at reflux or of pryridine hydrochloride at 200-220 C." "Reactions were carried out by heating at 115 C under vigorous stirring a hetrogenous mixture of substrate (1 mol), 47% HBr (5-10 mol) and hexadecyltributylphosphonium bromide (.1 mol)" "Indeed in phase-transfer conditions even aqueous HCl quantitatively converts alcohols into the corresponding chlorides." "Attempts to use concentrated HCl or HCl and NaBr failed [to cleave the ethers]" The basic reaction: ArOR + HBr --> ArOH + RBr I hope this sheds some more light onto this subject.
1) NO HEAT! 2)Cold is good 3)PTC's work if use properly. 4)PTC and HCL don't have the problems that HBr does. ================================ FROM "The Journal of Chromatograpghy science, Vol 29, 1991, page 267-271 "Thus the conjugated bond in isosafrole does not add HBr under the same conditions as safrole. Therefore, any isosafrole generated in via HBr elimination would not under go readdition and should accumulate in the reaction mixture." The conditions were: Bromination with 48% HBr (aqueuos). Stirred for 7 days @ room tempature. Quanities- 5 grams safrole, 25 mL 48% HBr. Quenched with 25 mL crushed ice and extracted with ether. Analysis at this points showed one major product. Amination was with 2 grams of the crude bromination product dissolved in methanol containing 40% aqueuos methylamine, 20 mL. It was stirred at room tempature for 4 days. For the amination the crude bromo compound was dissolved in 100 mL of methanol and 20 mL of aqueous methylamine. "In summary, these experimants show that HBr treatment of the various substitued allylbenzenes found in sassafras oil yeild predomintly the 2-bromopropane intermedites. Methylamine displacement reactions with these bromo intermedites yeilds the N-methyl-1-aryl-2-propaneamines as the major components." -----------------------------------------------------------------------------Drone 342: An idea of mine: To 235 ml of 10% methylamine in MeNH2 is added 0.89 g benzyltriethylammonium chloride and 18.6 g of crushed NaOH. The mixture is stirred magnetically at rt
for 1 h. 24.5 g bromosafrole is added, and is allowed to react overnight at room temperature with stirring. The next day, the solution is check ed via TLC to determine completion of the reaction. Once completion is determined, the inorganic material is filtered out, and the solution is washed with H2O. The solution is dried over MgSO4, and stripped in vacuo. The final product is subsequently distilled in vacuo. ------------------------------------------------------------------------------Rev drone: Alledgedly, chlorosafrole is readily prepard via safrole, HCl, and a PTC. This is good, if it is the case. Does anybody have notes on this? Chlorosafrole isn't as reactive as its heavier analogs bromo- and iodosafrole. However, I want to share with you all the magic of yet another phase-transfer catalylzed reaction: a variation of the Finkelstein reaction. Yes, a little quaternary ammonium salt, a dash of CaBr2 (I've heard rumors NaBr works too), and a person can readily convert alkyl chlorides to bromides without breaking a sweat. Synthesis 34, (1984) J. Chem. Soc. Chem. Comm. 1250 (1986) Isr. J. Chem. 26, (1985) 243 For those who prefer iodides: US Pat. 3992432 (1976) CA 72, 115271 (1970) J. Chem. Soc. Chem. Comm. 879 (1974) Synth. Comm. 16, (1986) 1029 ------------------------------------------------------------------------------J. Am. Chem. Soc., 1993, 115, 3071. "Surface-mediated reactions 3 Hydrohalogenation of alkenes". The article uses HCl in CH2Cl2 with silica or Al2O3 as the catalyst. The yields are excellent from what I remember, and react time quick. It seemed to me that the addition of water really fucked things up though. --------------------------------------------------------------------
-----------Osmium/Gnasher: Attempts to induce direct cyclisation of 2-hydroxy- or 6-hydroxysafrole by Adams method did not succeed due to the facile fission of the methylenedioxy group under HBr-AcOH treatment. However, the methylenedioxy group was stable up to 2hr in the presence of dry HBr in non-polar solvents such as CHCl3. Reaction of o-allylphenols with dry HBr a solution of the appropriate o-allylphenol (1mmol) in dry CHCl3 (15ml) at 0c was saturated with HBr. After keeping for 2hr, the reaction mixture was poured into ice water (50ml), the CHCl3 layer washed with water until neutral, dried (Na2SO4) and evaporated to furnish the corresponding o-(2'-bromopropyl)phenol in >95% yield as a dark brown liquid. The treatment of dillapiole with dry HBr gave a mixture of (I) and 2-bromodillapiole in CHCl3, it exclusively led to 2-bromodillapiole in DMF medium. When 2-hydroxy- and 6-hydroxy-safrole where treated in with dry HBr in CHCl3, the bromopropyl derivative was the main product (over 95%). Experimental: 2-Bromodillapiole Dillapiole (11.1g, 0.05 mol) in dry DMF (100 ml) was saturated with dry HBr at 0∞C. After keeping for 2hr, it was poured into ice-cold water (300ml), extracted with CHCl3, the organic layer washed with H2O until neutral, dried over anhydrous Na2SO4 and evaporated to furnish 2-Bromodillapiole (14.9g). Ref: Indian J. Chem. Sect. B, Vol 25, 1150-54 (1986) ------------------------------------------------------------------------------Ritter: There really is no point to fussing around w/ nasty HBr(g) solutions in DMF, AcOH, DMSO, etc to make bromosafrole.
This procedure works perfectly for smaller quantities of the 2brompropane. The thermal decomposition isn't much fun to deal with in quantities greater than 50g. Synthesis of 1-(3,4 methylenedioxyphenyl)-1,2-dibromopropane 18ml 48%HBr(aq), 10ml dH2O and Isosafrol(4.2g, .0258mol)is dissolved in 10ml ethyl ether with vigorous mag stirring. Rxn is chilled to -10'C (salt/ice bath). N-bromosuccinimide (4.6g, .0258mol) is slowly added portionwise over 10min and stirring is continued an additional 5min. Stirring is stopped and phases are separated. Aqueous layer is re-extracted w/ 10ml additional ether. Organic phases are combined, washed with 10ml 10% sodium bicarbonate then 10ml saturated NaCl soln and finally evaporated to yield 8g of title product as a thick greenish oil(90-96% yield). Product does not yield a solid crystal with any known crystallization solvent and also decomposes upon heating/ distillation therefor is best characterized as the monobromocompound. 2-Bromosafrole The above produced dibromo compound is carefully thermally decomposed in a standard vacuum distillation rig using an oil bath. Since copious quantities of HBr are produced as decomposition product it only make sense to use a water aspirator as vacuum source. When pot contents reach approximately 100∞C dehalogenation takes place and 2-bromosafrole starts to distil over. Depending on vacuum, rxn. may start at lower temp. Do not allow pot contents to excede 130∞C or glassware will rapidly fill with charcoal from uncontrolled decomposition! Yield of water white 2-bromosafrole was found to be in the 80-90% range. Another thing, I'm not much of a Uncle Fester fan however I must give him credit for his bromosafrole rxn which uses HCl to dehydrate 48% HBr. It really does work exactly as he describes it! Yields are high with very little unreacted safrole to separate from product and it can be scaled to any size imaginable.
------------------------------------------------------------------------------Easy Bromosafrole Synthesis by Berserker This is a revolutionary new method to halogenate ketenes with Markinokov selectivity, by reacting them with a phosphorus trihalogenide in the presence of silicon dioxide catalyst. To make others, just substitute safrole with 10 mols of another alkene. A suspension is made by stirring 5g of SiO2 (silicon dioxide) into a solution of 10 mol safrole in 25ml dichloromethane. To this, add a solution of 4 mol PBr3 (phosphorus tribromide) in 10ml DCM over the space of 10 minutes at room temperature. The solution is then stirred for around 30 minutes. The SiO2 (still in suspension) is filtered out and then washed with 15ml DCM. The combined liquid is washed with a 10% sodium bicarbonate solution, until no more gas is liberated, then twice with brine, and the organic extract is dried with sodium sulfate. The solvent is then allowed to evaporate, giving pure bromosafrole. Yields vary from between 50% to 100%. The SiO2 is 70-250 mesh powder, or can be prepared by grinding glass into a fine powder, and washing it with acid. Both silicon dioxide and phosphorus tribromide are unsuspicious chemicals, and can be ordered with ease from wellstocked chemical suppliers. Source: Journal of the Brazilian Chemical Society, Vol. 12, No. 5 (2001) ------------------------------------------------------------------------------Addition of Hydrogen Bromide to Safrole JCS 2008 (1938) A mixture of freshly distilled safrole (8.1g), a solution of perbenzoic acid in benzene (2cc of 0.3N), and benzene (100ml) was saturated with hydrogen bromide (2 hours). On each of the next 7 days perbenzoic acid solution (1ml) was added,
and the mixture shaken and kept for 17 days. The mixture was then washed with water, dilute aqueous sodium carbonate, and again water and the benzene layer was separated, dried, and distilled. The fraction (6.5g, bp 145.5-153∞C/9.5mmHg) was a colourless, mobile liquid and was identified as the known safrole hydrobromide; Robinson and Zaki (J, 1937, 2489) give bp 160∞C/16mmHg. The same beta-bromodihydrosafrole was obtained in both cases. The product was identical with the hydrobromide made under ordinary conditions and it did not react with potassium phthalimide, which is an indication of sec-bromide structure. ------------------------------------------------------------------------------1-(3,5-dimethoxy-4-hydroxyphenyl)-2-bromopropane a mixture of 4-allyl-2,6-dimethoxyphenol (2.5g, 13mmol), HBr (40%, in glacial acetic acid, 15 ml) was shaken and placed in a darkroom for a week. Then the bulk of the acetic acid was removed under reduced pressure and the remaining acetic acid was removed by co-distillation with ethanol. The residue was cooled in a ice-bath and slowly mixed with anhydrous K2CO3 (1-2g), and the resultant mixture was purified by column chromatography to obtain 1-(3,5-Dimethoxy-4-hydroxyphenyl)-2-bromopropane as a colourless oil (3g, 84%) Reference: J Chem Research (s) 1999 (2): 158-159 ------------------------------------------------------------------------------Derivatives of amphetamine. E. Muszynski (Akad. Med.. Warsaw). CA 58:3334 (1963); Acta Polon. Pharm. 18, 471-8 (1961) (in Polish). Safrole (10 g.) and 0.1 g. HgCl2 in 5 vols. AcOH was satd. with HBr. left 2 days at 0∞, neutralized with NaHCO3, extd. with Et2O, and distd. to give 73.3% 1-(3,4-methylenedioxyphenyl)-2-bromopropane (I), b15 162-5∞. nD16 1.5628. Methyleugenol (II) brominated analogously gave 36.5% 1-(3,4-dimethoxyphenyl)-2-bromopropane (III), b10 171-2∞ nD18
1.5614. I (7.3 g.), 36 g. 10% alc. NH3, and 0.8 g. Cu2O heated 7 hrs. at 160∞, alkalised to pH 9 with 40% NaOH. extd. with Et2O, and the ext. treated with 1:1 H2SO4EtOH gave 1 g. 1-(3,4-methylenedioxyphenyl)-2-aminopropane sulfate, and 4.2 g. unchanged I. II (2.9 g.) added at 0∞ to 9.3 g. 70% HBr, the mixt. left 12 hrs. at 0∞, hydrolyzed, extd. with Et2O, and the ext. distd. yielded 80.9% III. III (10 g.) treated similarly with NH3 gave 3.4 g. 1-(3,4-dimethoxyphenyl)-2-aminopropane sulfate and recovered 4.9 g. III. Acetyleugenol (63.6 g.) in 80 ml. AcOH oxidized 5 hrs. with 256 g. KMnO4, the MnO2 filtered off, the filtrate concd. to 800 ml., treated with 40 g. KOH, refluxed 90 min., acidified with 50% H2SO4 to Congo red, evapd. to dryness, and the residue extd. with Et2O yielded 41.5 g. homovanillic acid (IV), m. 142∞. IV (33.5 g.), 21.8 g. KOH, 25 ml. EtOH, and 55.3 g. MeI refluxed 1 hr., treated with 11 g. KOH, refluxed 1 hr., cooled, filtered, acidified with HCl, and extd. with Et2O gave 33.9 g. homoveratric acid (V), m. 97∞. V (20 g.) in 13 ml. AcOH passed at 430-50∞ through ThO2 on pumice yielded 30.8% 3,4-dimethoxyphenylacetone. -------------------------------------------------------------------------------
