(Ubiquitous Precursor Medal Winner)
09-18-01 13:42
No 214730
(Rated as: excellent)
Seen any interesting molecules around lately? This is one of the Hibbert ketones available from wood lignin. I'll call it syringyl-2-propanone, just as a friendly name. Seems like some beez might show enough interest in this, to wonder where to get it. You might say the woods are full of it, it grows on trees. This is another aspect of the lignin story; Post 190600 (halfapint: "Lignin Syringaldehyde Again", Novel Discourse).
Hibbert ketones are derived from lignin by a different route, not by the metal salt oxidation in alkali by which syringaldehyde and vanillin are obtained. Most often, Hibbert ketones are produced by alcoholysis with HCl, but that's not the way we should use, as I'll show you. The Hibbert ketone which corresponds to vanillin, I'll call vanillyl-2-propanone.
Now some folks around here might also see some good possibilities in this molecule. As foxy2 just showed us, on a LabTop scale no less, if you first alkylate the 4-hydroxy, and then brominate, the bromine will go in the 2-pocket, not the 5-hole. Sodium methoxide treatment will methylate the 2-bromo compound, leaving you just a reductive amination away from a real good time. There's got to bee a catch: oh, yeah. There's a catch all right. You have some more Hibbert ketones that look like vanillin, in their ring substitution pattern:
Well, if that's not bad enough, you also have some more, which have their rings substituted like syringaldehyde:
!!!
Ready to give up yet? I was going to tell you why not to use ethanolic HCl to chop lignin into Hibbert ketones. The reason, is that if you use alcohol, you get a Hibbert ketone that has the vanillin ring pattern, with oxygen on the propyl chain's 1 position, and an ethyl ether on the 2 position! You can't bust up that ether without also losing your phenol ether, a giant step backward. Useless. It's got a sibling, with the ethyl ether on the 1 slot, and the ketone in the 2 propyl position. Need I say, there are also syringyl versions of both of these? That makes four useless compounds, out of a round dozen Hibbert ketones! Horrible. So we don't use alcohol, we use dioxane.
Dioxane, by itself, well with a bit of water, will digest the lignin out of wood. But I would suggest not using wood. Use cardboard boxes, known as corrugated paper cartons on Sunday. I have been able to get more lignin out of cardboard boxes than from wood. I don't know why. Perhaps extra lignin is added as a "sizing", whatever that is. Perhaps it's a stiffening agent, or added for strength. Or could be, it's just concentrated in the production process. That's the key to your future success: you're in the recycling business now. We're talking about changing over ten per cent by weight of cardboard into precursors for psychedelic drugs. Antoncho, are our tanks in Berlin yet? As pOpEye said, "A drug war would be FUN!"
So after we extract the lignin with dioxane, we turn essentially all of it into Hibbert ketones by adding dilute hydrochloric acid to the dioxane. (My dioxane was cheap, for I distilled it out of ethylene glycol, actually antifreeze, with dilute sulfuric acid. It's wet; so?) I know, you're still dubious about our eight Hibbert ketones, how we are ever going to separate them. We can get them away from everything else by neutralizing the acid, condensing the solvents, then precipitating their condensation products with saturated sodium bisulfite, but how are we going to separate the 2 good ones from the waste? There won't be any waste, we're going to use them all.
To start with, the vanillyl-2-propanone is the lightest molecule there. In a fractional vacuum distillation, it will be the lowest boiling ketone, and it will come over first. One down, seven to go. The next three vanillin-like compounds can be combined. Then the syringaldehyde-like compounds will start to come over. The syringyl-2-propanone will again be the first of that lot. It is the most nearly finished of all these compounds, for it only needs 4-alkylation and reductive amination before it can go out the door. After that, the other syringyl compounds can also be combined, for it doesn't matter to us which ones they are. So we collect 4 fractions, in 4 bottles: vanillyl-2-propanone, the vanillyl keto-alcohols and diones (diketones), syringyl-2-propanone, and the other 3 syringyl ketones.
The mixed ketones we reduce to diols. Know what to do with vicinal diols? Of course, convert them all to 2-propanones, by treatment with lithium iodide or sulfuric acid! Then you can merge all the lignin aromatics into just 2 bottles, vanillyl-2-propanone and syringyl-2-propanone! That is how you can convert more than 10% of the weight of cardboard, into precursors.
So have I done this? No, I just now figured it out. I am easily excited, and I wanted to share this feeling with you while it is fresh. Plainly, I could be setting myself up, because I do not know the boiling points of these compounds. If the boiling points of the vanillyl and syringyl groups overlap, it would mess up my proposed separation. I also do not know the relative abundances of these ketones. This would vary with lignins.
The salient point is the reduction of the mixed ketones to diols, removing their differences by making them identical compounds. If the syringyl-2-propanone cannot be separated out by distillation, it will be reduced into the 2-propanol and probably wasted, when all the other syringyl compounds are converted into what it used to be: syringyl-2-propanone.
turning science fact into <<science fiction>>
(Newbee)
09-19-01 13:25
No 215103
You may be onto something huge here Pint 1/2
I remember getting completely over excited after reading a similar document on obtaining 3,4,5-TriMeOBenzaldehyde from sawdust of Eucalyptus Regnans. What was interresting about the doc is that it never mentioned any of the other goodies u mentioned. The sole product after treatment of the sawdust with nirtomethane was syringaldehyde, from where they obtained the 3,4,5-TriMeOBenzaldehyde.
About the card board boxes though....... How can you get more lingin from cardboard when you've never actually done this?
(Ubiquitous Precursor Medal Winner)
09-19-01 17:46
No 215144
(Rated as: excellent)
I haven't done the dioxane extraction of lignin. I have done the alkaline extraction of lignin, boiling sawdust (or cardboard) with KOH in a cast iron pot. This is in Post 190600 (halfapint: "Lignin Syringaldehyde Again", Novel Discourse). The oxidation of extracted lignin with nitrobenzene in ../rhodium /mescaly
An alternate to the vacuum fractional distillation may bee more practical, or more workable. A rapid initial separation of the vanillyl compounds from the syringyl compounds, even if it's crude, would be most helpful. I've realized that the fractional vacuum distillation would be a marathon session, watching drip-drip-drip all day. Even beez equipped for vac distillation, with a good column, rarely have a "cow" to change fractions without releasing the vacuum, so at least three interruptions of the run are needed to change fractions. Tedious, slow work.
A preliminary vacuum distillation of the ketones without a column, or a short column set for minimal reflux, may separate the lower boiling vanillyl species from the higher boiling syringyl compounds. Well, I know I'm making one distillation into three distillations, but it may be simpler by not requiring changing the receiver. When about half, or a little more than half of the ketone has come over, you look for a temperature jump. Taking the fraction when that happens, you consider the ketones remaining in the flask as syringyl ketones, as you save the vanillyl ketones for redistillation.
Then you rig your more efficient (slower) column, to get your (hopefully) syringyl-2-propanone as the first fraction. It is advisable to distill the remaining syringyl ketones then, for undoubtedly there will be some crud left in the pot after they've come over. You wouldn't want that crud complicating your successive reactions.
Then in the boiling flask you place your previously distilled vanillyl ketones, take the first fraction as vanillyl-2-propanone, and stop. There is no need to redistill the previously distilled vanillyl ketones, unless you feel the crude first distillation may have mixed a bit of syringyl ketone in.
I've complicated the distillation procedure in hopes of saving a little time. Doing this may or may not be appropriate, depending on a bee's facilities and experience. Taking the trouble to note the temperatures at which fractions come over with your vacuum, will make it much easier the next time, and you'll get it down until you are churning out these ketones routinely. They're not rare, you know, and they're not that hard to get, the second time. You don't have to expose yourself by dealing with snooty or suspicious vendors, right?
Antoncho and I, among others, have found a few techniques of chemical separation of syringaldehyde from vanillin. It would be splendid if something like differential solubility in concentrated alkaline or ammoniacal solution, would precipitate all the syringyl ketones as a solid mass, while leaving the vanillyl ketones in solution. But the presence of those side-chain alcohol groups on half these ketones, gives me no confidence in precipitation techniques.
We know the desired separations can be made. As a last resort, preparative column chromotography will separate all these ketones. Very probably, fractional distillation will give us satisfactory separation, as proposed here. There must be chemical techniques to short cut these exhaustive methods, but we have to discover them by experimentation. Nobody's going to do this work for us. We have to bee the pioneers of our own science. And, by the way, Half-a-Pint isn't going to be able to do all this experimentation alone. There just isn't enough time. Can we have a bit of hands-on participation here?
Edit: Another path might bee just to hydrogenate (or otherwise reduce) everything, all the ketones, most of which will form vic-diols, vicinal di-alcohols. Then treatment with concentrated sulfuric acid or lithium iodide would give 2-propanones from all the Hibbert ketones that weren't 2-propanones before. The two ketones which were 2-propanones before will have been reduced to 2-propanols (and may now be sulfonates). If the latter were only a small constituency of the original ketone mix, they might be discarded, giving you the lion's share of your lignin as 2-propanones without distillation, with only bisulfite purification. The resulting mix of syringyl-2-propanone and vanillyl-2-propanone will certainly be separable, quite easily, by differential solubility in hot base, just like syringaldehyde falls out of a cooling solution with vanillin. No still needed, OTC, you can cook your way home.
turning science fact into <<science fiction>>
(Official Hive Translator)
09-19-01 18:52
No 215157
GREAT!
Especially the last proposition - it really looks slick!
BTW, what do you think is so special about dioxane as the xtrctn solvent? (SWIM just happens to know a place where you can get a kilo for like 50 cents - yes, that happens sometimes where i live :):):) I mean - is it specifically selective for those ketones or something?
Antoncho
(Ubiquitous Precursor Medal Winner)
09-19-01 21:13
No 215208
I'm just going by what Prof. Elder at Auburn says in that lignin link above. Dioxane is about like THF as a cyclic ether, but much cheaper. And quite easy to make from auto antifreeze, ethylene glycol, as I mentioned. I'd consider that as OTC. My last sentence was of course exaggeration. You do need a still of sorts to make dioxane. Also you will need an alkylating agent, and you can't make that without a still. To make dimethyl sulfate or diethyl sulfate, you need vacuum with your still. Alkyl halides can bee distilled without vacuum, though. I have made lots of stills from jars, bottles and tubing: put heavy-duty foil around the bottom of the jar to distribute the heat, and/or use a bath of cooking oil, and you have an OTC still. Making the condenser calls for ingenuity, but that's the fun part. Leak proofing a jar lid to hold hot vapor is the biggest challenge. I found you can solder a short length of small copper or brass tubing into a jar lid, and fasten your plastic tubing to that. Ah, the good old days.
Reducing the ketones to the diols can be done with about any reducing agent, like a metal in acid. To get the propanone from this, though not in my experience, doesn't seem too hard in the old Hive posts. Lithium iodide isn't OTC, it's watched where I am, but photo batteries containing lithium are not, and HI gassed into a nonpolar solvent holding your lithium will produce it anhydrous. Sulfuric acid, as the alternative, is OTC. In the vanillyl propanone case, bromine is next required, and several threads on making OTC bromine are available here.
You posted a reference Post 198026 (Antoncho: "Re: High-yield 3,4,5-TMB synth from vanillin (Russian)", Novel Discourse) which refers to the separation of vanillin from syringaldehyde after bromination of the vanillin, by precipitation of the brominated compound from acetic acid/glycol/water. It does seem this might prove very relevant here!
Is it indeed necessary to separate it? The reference you gave refers to bromination of vanillin in the presence of syringaldehyde. Caution, we have another shortcut coming up. We may have a path to TMA here without separation of the ketones. Heating with concentrated KOH will (1) substitute the 5-Br with 5-OH and (2) leave this 5-OH as the potassium phenolate salt and (3) leave the 4-OH on both types of ketones as the potassium phenolate salts.
Being very specific here, we now have one propanone with the ring substitution pattern 3-methoxy, 4-oxo-potassium (whatever you call it), and 5-oxo-potassium, which was our vanillyl ketone. In the same pot with it, we have a propanone with 3,5-dimethoxy and 4-oxo-potassium, the potassium salt of our syringyl ketone. What if we just methylate the hell out of the whole shebang? We get one component in our pot: 3,4,5-trimethoxy-phenyl-2-propanone. Amounting to most of the lignin originally present! Now does that sound like a winner?
3,4,5-TMA is only a reductive amination away. In my ignorance, I would suggest ammonium formate in formic acid and water, with Urushibara nickel for a catalyst. Same thing as bubbling ammonia through aqueous formic acid, right?
That last proposition has got my head spinning too. Look out world, we're working again.
Edit: In my search for your bromination-separation post, I found the iodovanillin thread foxy2 clinched up with that patent now at ../rhodium /iodovan
turning science fact into <<science fiction>>
(Newbee)
09-19-01 22:45
No 215248
Hmmm.. I wonder. Wasn't it possible to get 4-hydroxybenzaldehyde out of conifer and grass lignins? Couldn't it be halogenated at position three and the halogen converted to a hydroxyl group, with methods well-known and discussed. Oh my god, 3,4-dihydroxybenzaldehyde! Some bastard could methylenate this to piperonal... and we all know what the corresponding ketone is. Tell me, why not?
understanding is everything
(Ubiquitous Precursor Medal Winner)
09-20-01 00:38
No 215277
Yeah you right. Having the aldehyde, though, won't give you the ketone, without sending you on a merry chase for nitroethane. That you can't buy. We have discussed lots of ways to make it around here. Not one of them is quick and clean and easy and cheap and high yielding, though; in fact, most ways to nitroethane are a real pain.
After you condense your aldehyde with nitroethane, you don't have to reduce (Fe/AcOH) to the ketone, and then reduce again (reductive amination) to the amine. You can just reduce the nitropropene formed in the Henry condensation straight to the amine, if you use a very strong reducing agent.
This nitroethane biz is the best reason to avoid aldehydes, when you can get the ketones instead. That's why my interest is shifting from syringaldehyde to these Hibbert ketones, this thread. The same dioxane extraction and HCl treatment will produce para-hydroxy-phenyl-2-propanone, if you use it on grass instead of wood. That would, in its turn, be the lowest boiling of all your (twelve!) Hibbert ketones, and I suppose you would want to throw the rest away. (Sigh. Three others, boiling just above that, would do you good, reduced to the diol then converted to the propanone as above, giving the same compound as your low boiler.) Then you could follow your bromination plan (better, the iodine patent linked above), treat with KOH for the hydroxyl, and methylenate with DCM (better, methylene bromide, or one of the heaviest liquids this side of Mercury, methylene iodide) to get MD-P2P. Get a bagging lawn mower, to keep you in Ecstacy for the rest of your days.
turning science fact into <<science fiction>>
(Hive Bee)
09-20-01 01:42
No 215288
Some bastard could methylenate this to piperonal... and we all know what the corresponding ketone is. Tell me, why not?
and
Yeah you right. Having the aldehyde, though, won't give you the ketone, without sending you on a merry chase for nitroethane.
According to Strike (in TSII), piperonal can be converted via the Grignard reaction into isosafrole. Nitroethane is merely the easiest method of converting piperonal into something more interesting, there are probably several other routes besides the one that Strike wrote of that haven't been posted on the Hive yet
(Newbee)
09-20-01 20:53
No 215670
My point was that one could get the phenylacetone from the hibbert ketone route analogous to the way one would get the benzaldehyde thusly avoiding water-hating grignards or the trouble of making nitroethane. Well, you said it already.
understanding is everything
(Ubiquitous Precursor Medal Winner)
09-21-01 05:01
No 215788
Oh. Well, if you had been plainer about finding that ketone in grass, I wouldn't have had to spell it out. It is a good point, so you could have been more assertive about bringing it to our attention. The Half-a-Pint Correspondence Institute for Braggadocio and Self-Aggrandizement is accepting applications daily.
Edit: Experimenting last night, I found the "organosolv" extraction of lignin gives yields much lower than I'd expect from alkaline extraction. I used dilute (15%) dioxane in water, for there was little dioxane on hand; also, I tried denatured alcohol. Using straight dioxane could give a very different result. Possibly we can uncouple the lignin extraction from the lignin hydrolysis, and use procedures optimized for each step, if the lignin can bee isolated between stages. That makes me curious about the copper-ammonium hydroxide isolation of lignin, which dissolves out the carbohydrates (cellulose and its relatives) and leaves the lignin, which (after washing) we could then take up in dioxane/HCl (aq) and get our Hibbert ketones. Alkaline extraction is our fallback; we know that works, and works well, but will introduce the added complication of neutralizing the alkali then removing lots of water, before acid hydrolysis to Hibbert ketones.
I don't know whether to actually boil the lignin to get these ketones. The reference doesn't say, but I am very superstitious about boiling potential psychedelic amphetamine precursors, aromatic ethers that they are, in strong mineral acids, for fear of losing the methyl ethers off the ring. The reference does say the alcohol versions of Hibbert ketones, are obtained by boiling in ethanol/HCl. So it must be safe up to 78o. Last night, I saw a distinct color change on adding HCl to a warm dioxane/water solution of lignin. It went from midnight brown, to the color of a bay horse, immediately. But I don't expect that the hydrolysis of lignin would take place immediately. I held it at 80o for two hours. Stay tuned for further developments. Or better yet, help!
turning science fact into <<science fiction>>
(Hive Bee)
09-21-01 05:30
No 215794
This is really nice. Seriously, that's all swic can say, he just really likes it.
We're talking about changing over ten per cent by weight of cardboard into precursors for psychedelic drugs.
This comment will forever by burned onto the right side of swic's brain.
(Ubiquitous Precursor Medal Winner)
10-06-01 09:12
No 220867
Beez get tired real quick of hearing theory from one who can't interact with current literature. They like lab talk. Anyway I'll bring you all up to speed on the current version, latest and greatest, on how the great preponderance of lignin could be used as precursor. To this challenge, I submit the following.
Steps.
1) Dissolve lignin. Use KOH in water.
2) Hydrolyze lignin. Use HCl in dioxane.
3) The resultant Hibbert ketones are all reduced to the corresponding diol, except the mono-ketones, which are reduced to the secondary alcohol.
4) Treatment with 15% sulfuric acid gives mono-ketones from the diols, not from the (single) alcohols.
5) Bromination with bromine and hydrobromic acid gives bromo compounds from the alcohol, but does not affect the ketone side chain. The rings with three substituents, the syringyl nuclei, are not brominated. The rings with only two substituents, the vanillyl nuclei, are 5-brominated.
6) Condensing the ketone with hydroxylamine separates ketone species from the brominated side chain compounds. The latter are removed, treated with sodium azide, then returned (as the hydrazide) into a solution with the oxime.
7) All the compounds are reduced to the respective amines.
8) The ring brominated compounds react with KOH to give the phenols.
9) The phenols are all methylated with dimethyl carbonate (preferably) to give the single constituent 3,4,5-TMA.
Lots of steps. Tricky ordering. Probably do it, unless somebody can see why not. Didn't say solvents etc.; and yes it matters. But that's the current outline, not limited to the semi-micro scale. Didn't say scale. Laterz
turning science fact into <<science fiction>>
(Ubiquitous Precursor Medal Winner)
10-07-01 01:41
No 221039
Touch of pyridinium dichromate in DCM after step 4 is said to oxidize P2Pol's to P2P's in high yields. That would satisfy the principle of Occam's Razor, about not multiplying entities unecessarily.
Pyridine ain't easy to come by, unless you decarboxylate niacin (a B vitamin, nicotinic acid, pyridine-3-carboxylic acid.) Saves using another less frequently encountered reagent later, the sodium azide found mostly in air bags; saves the separation of brominated side chain species, and indeed their formation, HBr being unneeded in the bromination step this way. Simplifies a lot; just wish it didn't tend to being an exotic chem. Chromic acid isn't too hard to find. Half-a-Pint's notion of industrial scale is like, industrial. So what's the preparatory, chem eng oxidizer to replace the academic lab's use of pyridinium dichromate in making P2Pols to P2P's?
Real chemists will hate this synthetic procedure anyway, keeping a bunch of ingredients together in the same pot as you bash one part and another, to get them all to converge on the same product. Chemical technologists delight in ruffling academic feathers in coming up with a production technique, with shortcuts which should never have worked, but save loads of grief when they do prove to work.
Real chemists would prefer to isolate each of the eight Hibbert ketones, and treat each of them individually as a pure compound. That would make this into a three day run at least, meaning it would never be adopted in the field. That doesn't fit my interest in this affair. What's needed is a robust, repeatable procedure which can bee reduced to a cookbook technique to give predictable yields. If a convergent synthesis means sloppy chemistry, what's the tradeoff? Is there anything to interfere with our doing the steps and churning out the product?
Use of a P2Pol oxidizer would give this revision:
1) Dissolve lignin. Use KOH in water.
(you have polymeric lignin.)
2) Hydrolyze lignin. Use HCl in dioxane.
(you have 8 Hibbert ketones, pictured above.)
3) The resultant Hibbert ketones are all reduced to the corresponding diol, except the mono-ketones, which are reduced to the secondary alcohol.
(your side chains have diols and alcohols.)
4) Treatment with 15% sulfuric acid gives mono-ketones from the diols, not from the (single) alcohols.
(your side chains have 2-ketones and 2-alcohols.)
4a) Basic conditions are needed to bee introduced at this point, for the nominally 2-alcohols are actually 2-sulfonates with the acid present.
5) Oxidation with pyridinium dichromate in DCM (or reasonable facsimile thereof) gives mono-ketones from the remaining alcohol side chain.
(your side chains are all 2-ketones now.)
6) Side chains are now uniform and stable enough so we can do all the shuffling on the rings. I'll take iodination over bromination generally; iodine is more initially expensive, but is a bit easier to reclaim than bromine.
(5-iodo or 5-bromo vanillyl ketones now mingle in the pot with your syringyl ketone.)
7) Sodium methoxide treatment now gives a single-component pot of syringyl ketone, to make the chemists happy. There is something to isolate, to purify, to filter, wash, distill, weigh and measure.
ed: Single component pot doesn't mean there aren't salts and other organics present. To me, that means everything which isn't that, can now be discarded to recycling. Yield may be determined at this step.
8) Now you have the desirable option on the 4-alkylation, since you used sodium methoxide rather than KOH in the last step. Feel free to build the 4-allyloxy or the 4-isopropoxy 3,5-dimethoxy amphetamines that Shulgin never got around to.
9) Condense the ketone with ammonium formate in the Leukart reaction. Or any of your favorite reductive aminations.
Such is my concession to the grumpy chemists among us, who like stuff like pure compounds and all. This version converges all those ketones to a single compound by the 7th step, less tar, less mess.
turning science fact into <<science fiction>>
(Old P2P Cook)
10-07-01 03:38
No 221059
At step 5, instead of oxdizing the alcohol in the ketone/alcohol mixture to ketone, use bisulphite to separate the ketone/alcohol mixture into two process streams. Proceed with step 6 on the separated ketone, save the alcohol for possible reintegration into the process stream via the oxidation.
(Ubiquitous Precursor Medal Winner)
10-07-01 03:51
No 221067
Shucks, that oxidation was the novel feature of this latest rev. Diverting the alcohol to oxidation, by harvesting the ketone at this point with its bisulfite precipitation is a sensible alternative if the oxidation gets complicated. But what if it can get done with DMDO, or something that's not pyridinyl dichromate? How do such questions get answered, I wonder.
Later: If you want to save out your ketone as it is made, sure you can get a first crop out after Step 4, as the bisulfite, oxime, phenylhydrazone, whatever. The remaining alcohol remains in the solution, which may be reduced in volume, and then taken up in DCM for the oxidation. Then the same derivative is taken from the new oxo compound, and matched with the previously extracted bisulfite, oxime, phenylhydrazone, etc. (But you have a mixture of ring forms, requiring ring halogenation prior to alkylation to regularize ring configuration, as the syringyl ketone S2P.)
I was afraid that something in my cavalier oxidations and reductions with ketone compounds present had hidden a new miracle polymerization formula, or something. So fallbacks are good, save what you got is good, especially in the exploratory phase of this potentially industrial process.
Primitiveness pondering: Wonder if the products remaining in the pot after boiling lignin from a now vanished formic acid solution, would contain, or be largely comprised of, these same Hibbert ketones. I would expect the benzoic acids might arise, particularly if peroxides are allowed to build up near the end of the distillation. Hm, don't allow that, then do you get ketones? No doubt, formic acid's a stronger oxidizer than HCl in dioxane. That kind of thing's worth a try, though. In a suspect distillation such as this, I should interrupt it and cool the flask at the 3/4 point, to which I would add a few grams of ferrous compound, then continue the run, with lowered probability of being blown up by hypothetical peroxides.
turning science fact into <<science fiction>>
(Ubiquitous Precursor Medal Winner)
10-13-01 17:35
No 224032
Hit a snag.
../rhodium /iodovan
The process is not useful with substituents such as... ketone groups with an alpha hydrogen, which either react with the reagent or strongly de-activate the ring. Ketone groups are deactivating, as are aldehyde groups, but ketones containing an alpha hydrogen would react with the iodinating agent whereas the aldehydes would not... Weakly de-activating groups such as aldehyde groups do not interfere with iodination.
I bet this problem would apply to ring bromination also, as well as to attempted ring iodination. While the aldehyde as well as the isopropyl ketone are both deactivating, as regards ring halogenation, the ketone has another preferred place for that halogen to go: substituting that alpha hydrogen on the side chain. Not good at all. Times like this make me wish I had taken some organic chemistry courses.
So while you can iodinate, or brominate, vanillin (the aldehyde) in the presence of syringaldehyde, in the quest of a one pot synthesis from lignin, the same does not hold true for the corresponding isopropyl ketones. At this point, there doesn't seem to bee any way to get around separating the vanillyl-2-propanone fraction from the syringyl-2-propanone, and running separate batches.
From the looks of the above quote, I'll have a hard time figuring out what to do with the vanillyl fraction, to keep the halogen from substituting on the side chain, in the attempt to halogenate the ring. If the isopropyl ketone were derivativized, say to the oxime or even to the amine (as protected by acetylation), would its alpha hydrogen remain as labile, and subject to replacement by halogen?
help --- my experimental batch was just about ready to get halogenated...
turning science fact into <<science fiction>>
(Stoni's sexual toy)
10-13-01 22:22
No 224088
I thought the haloform reaction isn't gonna happen in an acidic medium?
(Ubiquitous Precursor Medal Winner)
01-20-02 17:32
No 258674
(Rated as: good idea!)
Circumstances have forced delay in the practical experimentation with syringyl-2-propanone production. In the interval, I have become convinced of the general applicability of thermal rearrangement to ketones of the Hibbert syringyl diol. I expect this to occur in reflux at ambient pressure followed by distillation at reduced pressure. (Any oxidation of the propan-2-ol, if this is used, should happen after the reflux, but before the distillation.)
I am more hopeful for vanillin-2-propanone bromination, selectively in the presence of syringyl-2-propanone, than a gloomy post above suggests. In acid medium. Using Br/HBr or possibly dioxane dibromide I think I could move ahead. Antoncho's efforts have just paid off for sodium methoxide in Post 214730 (halfapint: "The Hibbert Ketones of Lignin", Novel Discourse). Some of the sequencing of this complex rxn should now bee recalculated.
Try this:
1) Dissolve lignin. Use KOH in water.
(you have polymeric lignin.)
2) Hydrolyze lignin. Use HCl in dioxane.
(you have 8 Hibbert ketones, pictured above.)
3) Reduction: The resultant Hibbert ketones are all reduced to the corresponding diol, except the mono-ketones, which are reduced to the secondary alcohol.
(your side chains have diols and alcohols.)
4) Refluxing the mixture after distilling solvents and filtering off salts, dehydrates the diols to propan-2-ones.
(your side chains are 2-ketones, with some propan-2-ol.)
5) Oxidation with dichromate gives mono-ketones from the remaining alcohol side chain.
(your side chains are all 2-ketones now.)
5a) Isolate the ketones as the bisulfite addition products.
6) Halogenation: 5-Halogenation is performed on the vanillin ring, without regard to the presence of syringyl ketone.
(5-iodo or 5-bromo vanillyl ketones now mingle in the pot with your syringyl ketone.)
7) Methoxylate: Sodium methoxide treatment now gives a single-component pot of syringyl ketone.
7a) a good place to purify by distillation at reduced pressure.
8) Alkylate: 4-alkylation provides 4-alkyl-3,5-dimethoxyphenyl-2-propanone.
9) Aminate: Condense the ketone with ammonium formate and formic acid in the Leukart-Wallach reaction. Or any of your favorite reductive aminations, though reducing an oxime or hydrazide intermediate will give better yields at normal pressure, than ammonia or ammonium acetate or even benzylamine.
Then I'll have to decide on solvents, reaction conditions and workup. This sorcery becomes like working for a living, after while.
turning science fact into <<science fiction>>
(Stranger / Eraser)
07-06-02 17:55
No 329329
Halogenation of the ketone in acidic media should produce the mono-haloketone.
This might offer a solution:
"Bromination of acetophenones in the presence of AlCl3 prevents bromination of the lateral chain."
Org. Synth. 40,7,1960