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All 49 posts Subject: Please criticize: route-Acetaminophen to DOB/DOC Please login to post Down

ning
(Hive Bee)
10-26-03 03:52
No 466801
      Please criticize: route-Acetaminophen to DOB/DOC

Ning was thinking of a fairly simple, OTC route from acetaminophen to DOC. Please give review and criticism, so ning can improve it.

Step 1: hydrolyze acetaminophen to p-aminophenol.
Refluxing in HCl or NaOH, ala Rhodium.

Step 2: oxidize p-aminophenol to quinone.
Using MnO2 from battery. Reflux, ning supposes.

Step 3. Add HCl(or HBr) to quinone to yield chloro (bromo) hydroquinone.

Step 4. Methylate chlorohydroquinone to p-dimethoxychlorobenzene
Ning knows how to do that...

Step 5. Alkylate with chloroacetone to yield DOC-P2P.

Step 6. Reductively aminate any way you see fit.

Ning has seen documents giving at least hints that all of these steps are feasible in decent yields. Molar throughput yield of about 20-25% from acetaminophen are expected.

So there it is. Any thoughts? The chloroacetone alkylation should be much higher yielding than the one on rhodium's p2p document, since the ring is activated and steric effects give the acetone essentially only one place to go.
A strong catalyst should be used, and not too high heat, as ning has heard that yield is lowered by a type of decarboxylation reaction when alkylating with acetone-like ketones at high temperatures.

Lilienthal
(Moderator)
10-26-03 10:46
No 466836
User Picture       No reply without links and references...

No reply without links and references...

Lego
(Hive Bee)
10-27-03 14:22
No 467006
      Some critics&proposals

Why start from Acetaminophen?
Hydroquinone is OTC and only needs one step to benzoquinone.
https://www.rhodium.ws/chemistry/benzoquinone.html

Step 3&4 can bee performed in a one-step reaction.
Dissolve benzoquinone in MeOH saturated with HBr and you will get 2,5-dimethoxyphenylbromide (unfortunately no exact procedure was found, as soon as Lego has the detailed procedure it will bee posted).

The next step would be the formation of 2,5-DiMeO-P2P. Lego suggests the following method: Post 464635 (Lego: "P2P from bromobenzene/CuI/Acetylacetone", Methods Discourse)

Reductive amination and halogenating the 4-position will yield the desired 2,5-dimethoxy-4-halogen-amphetamine.

PS: UTFSE and search for chloroacetone, you will see it is no fun to work with this compound.

The candle that burns twice as bright burns half as long

Rhodium
(Chief Bee)
10-27-03 17:39
No 467041
User Picture       The use of acetaminophen (a.k.a. paracetamol)

The use of acetaminophen (a.k.a. paracetamol) as a drug precursor has been discussed before in this thread: Post 224004 (fructose: "route from acetaminophen (paracetamol)", Chemistry Discourse)

ning
(Hive Bee)
10-28-03 14:10
No 467262
      indeed

...but they talk about diazotizing the amino off, before going off on some tangents. The essential and beautiful thing about the quinone route is that it requires nothing wierd like nitrites, and gets you SOOO close to the DOC/DOB precursor you need. Only heating in H2SO4/MnO2 followed by HCl or HBr, people! Out of frickin' tylenol! The alkylation looks to be the tricky part, but it too is beautiful--by both activating and populating the ring first, there's pretty much only one spot it can alkylate the acetone into, so the ususal stuff that kills the efficiency of the alkylation doesn't matter here. Ning is aware of the nastiness attributed to chloroacetone, although has no personal experience with the stuff. Currently ning is searching for a good way to make it. TCCA seems promising. Ning has a great paper where they allylate benzene with ~80% yield, but allyl chloride is troublesome to make, so if acetone will do, ning would prefer it...
btw, ning promises to post that paper too, of course...

And yes, ning has heard quinone is commercially available, but ning's dream is to make a (hypothetical) synth that is completely OTC from only the most common ingredients, if possible, so any bee, anytime, anywhere, can whip up a batch of something sweet.
250g acetaminophen is about 7 to 10$. If that was converted to DOC in 20% yield, you would have around 7000 full-blooded doses. It may be less economical than buying quinone, but it would appear to be still very easy, and ning thinks much safer and more accessible. Lets take some heat off the photo guys, and save our purchases for PdCl2 and such, ne? wink Of course, if you are thinking industrially, it is different, but then, you can surely get what you need by different means.
If you are dreaming personally, or for that select circle of friends, one bottle of tylenol will take you a looooooong way. So let's not be too picky. wink

ning
(Hive Bee)
10-28-03 14:15
No 467263
      By the way, Lego...

What is this acetylacetone? it sounds like you would need chloroacetone to make it...
Maybe it's like acetic anhydride, except with acetone on one side?

Lego
(Hive Bee)
10-28-03 14:47
No 467275
User Picture       Try harder...

What is this acetylacetone?

Is it so hard to use the 'image search' of Google? Entering 'acetylacetone' will answer your question!
Acetylacetone is OTC, it is used as a solvent wink .

The alkylation looks to be the tricky part

Methyl tosylate is OTC and compared to other methylating agents quite harmless, yields should be good. Lego has posted two more OTC methylating agents, one of them will work for your purposes.

Step 1: hydrolyze acetaminophen to p-aminophenol.
Refluxing in HCl or NaOH, ala Rhodium.

Could you please give the link? Lego is too lazy to search it wink .

The candle that burns twice as bright burns half as long

ning
(Hive Bee)
10-28-03 15:20
No 467283
      Proposed procedure: Acetaminophen-->quinone OTC

To 50 mL H20 heated to 50C and stirred, add
4g H2SO4
2.3g crushed acetaminophen tablets (A)

After A has dissolved as much as it will, add

1.4g (anhydrous. equiv. wt.) MnO2

Let stir for several hours, or until color change is complete. (ning assumes quinone is colored)

Slowly add 4g NaHCO3 and let solution cool. Shake with xylene, (or ether, whatever), strain solids, separate.
Quinone should be in xylene layer.

What happened?
This procedure combines extraction, hydrolysis and oxidation in one step. The formula goes something like this:

Hydrolysis: Ph(OH)NH-Ac + H2O (acid) --> Ph(OH)NH2 + AcOH
Oxidation : Ph(OH)NH2 + MnO2 + 2H2SO4 --> O=C(CHCH)C=O + MnSO4 + NH4SO4
Cleanup   : MnSO4 + NH4SO4 + AcOH + 2NaHCO3 --> MnSO4 + NH3 + NaOAc + NaHSO4 + 2H20 + 2CO2 (?)

As far as ning knows, only quinone will be appreciably soluble in nonpolar solvents.

All OTC, if it works. No chromiums or nitrites.

Now, before smoeone gets mad, ning does have one paper on this, involving MW chem. ning will post it, but it isn't really all that relavant, the most important phrase (from memory) being "MnO2 is a gentle, effective oxidizing agent which will convert alcohols to corresponding aldehydes without overoxidation to carboxylic acids". They also hint that their silica supported, solvent-free microwave oxidation is more clean, but not higher yielding than the corresponding with-solvent, standard-heating procedure. Since the solvent procedure permits combining hydrolysis, and since ning's little tests indicate that dry battery MnO2 isn't really dry, and heating in the microwave without solvent to even out heating produces hot spots that rapidly cause the A/p-aminphenol to burn with a strange smelling and very persistant odor, ning doesn't want to use their procedure.

Sr.L, want to know ning's reference? Chemistry of organic compounds, by Carl R. Noller, published by saunders, 1951.
It has a most unique stream-of-consciousness-oh-let-me-see-what-compound-shall-we-talk-about-next style ning has never before seen in a chem book.
Here is a little quote in the quinone section:

"quinones are formed also by the oxidation of aminophenols and diamines, because the intermediate quinonimines are hydrolyzed rapidly in aqueous solution. [AND THEY SHOW p-AMINOPHENOL TURNING INTO QUINONE] Quinone is a generic term for the above class of compounds but frequently is used as a specific name for p-benzoquinone. The name quinoyl was assigned to this compound when it was first obtained by the oxidation of quinic acid extracted from cinchona bark. Berzelius later changed the name to quinone. it is prepared commercially by the oxidation of aniline with manganese dioxide and sulfuric acid
[They show the reaction]
Quinone is a bright yellow solid with a sharp odor. Its reactions are those of a,b-unsaturated ketones, involving 1,4 addition, rather than those of aromatic compounds. If the intial product can rearrange to an aromatic compound a substituted hydroquinone results.
[HERE THEY SHOW HCl ADDING TO MAKE CHLOROHYDROQUINONE]"

This is all one unedited passage. So ning isn't really smart at all, ning just has a good book. tongue Sr. L, are you satisfied yet? smile

Rhodium
(Chief Bee)
10-28-03 15:28
No 467285
User Picture       Synthesis of Acetylacetone
(Rated as: excellent)

Preparation of Acetylacetone
K.K. Georgieff
Ind. Eng. Chem. 49(7), 1067-1070 (1957) (https://www.rhodium.ws/pdf/acetylacetone.synthesis.pdf)

pericles
(Newbee)
10-29-03 02:59
No 467421
      Excellent!

It would be wonderful to see this verified. I'd be thrilled to see an OTC preperation of quinone. Keep up the good work!

ning
(Hive Bee)
10-29-03 17:27
No 467577
      Lego:

thanks for the ideas. The "a la rhodium" refers to something rhodium posted in that other thread on acetaminophen, just to reflux in NaOH or H2SO4. Ning decided H2SO4 because it fit with the oxidation part better.

Update:

Ning did a little test run, following ning's proposed procedure, except 100mL water was used instead, and no heat was used. Hydrolysis didn't seem to change anything, but soon after the dried battery crap was added, the solution turned orange-brown and made a very strange, unpleasant smell. It was left to sit overnight and then ~100mL xylene was added. The water wasn't basified, as it seems bases will make quinone water soluble (although whether NaHCO3 will is questionable). The mixture was shaken like a red-headed stepchild and left to settle. the xylene layer turned a wonderful bright shade of YELLOW. *flips to merck index* Says yellow crystals here. Hmmm...
Here is where the disasters started.
First, as ning had read that batteries contain other crap than MnO2, (like carbon), and that MnO2 has water with it (MnO2 * ?H20), ning worried that maybe there wasn't enough in there (Yield-greedy bastard wanted something stellar to post at *The Hive*). So more was added. Through the xylene layer. Suddenly, a huge emulsion formed. Seems the xylene coated the powder(?)--battery gunk isn't exactly soluble in water, but for some reason you can...suspend it in water--it moves when pushed with water, you can wash it out of glassware, etc. With xylene, you can't--it just ignores it completely. So the crap coated everything in the beaker. Fine, thought ning, and went to bed.
Next morning, naked to the underwear, ning tried to filter the shit through a buchner to remove most of the gunk. Stupidly, the gunk was poured into the funnel first, before attaching the vaccuum hose to the flask. While attaching the hose, ning slipped and in a flash, everything was covered with carbon powder, manganese, xylene, and dilute sulfuric acid. Howling and cursing, ning wiped up the gunk off books, desk, glassware, and almost nude body. The remaining sludge was filtered as fast as possible and stashed in a flask.
Then the second stupidity happened. Ning took the glassware into the shower. Hoping some warm soapy water could clean off both of them together (they spend so much other time together after all), ning washed the flasks. Only problem was, it seems the battery gunk likes sticking to bathtub plastic (let it be a lesson to ye!), and the action of showering tracked it everywhere. The rank smell of xylene was everywhere.
So finally, after drying, ning had to use some precursor (Bar keeper's friend works well, actually) to clean other precursor (ugh, it's so black) off the communal facilities. Scrub, Scrub, Scrub. And this was with an exam in just 5 minutes.

To cut a long story short, everything was more or less cleaned up, ning's room still smells of solvents, (and ning used xylene because it was less volatile....:-< just imagine if it was ether :-O)
But this story may have a happy end. Still much yellow oil remains, in a flask to separate. With most of the black gunk filtered out, it seems the emulsion has gone away, and ning can use the sep. funnel to take off the rest.

So, after the laughter dies down, ning has some questions to ask the HIVE at LARGE:

1. Why is ning such an idiot? (never mind)
2. What is the formula of battery gunk? More specifically, how much carbon shit is in there? Perhaps it could be calculated by measuring its resistance?
3. What is the water attached to MnO2? Anybee know?
4. What conditions are necesary to add HCl/HBr to the quinone? Heat? Time? Just contact?
Ning knows it is possible, but as usual, conditions were not specified.
Ning thinks to shake the xylene oil with Aqueous HCl, which should cause the stuff to come out into the water as chlorohydroquinone. should be easy enough to test--add, shake, oil goes clear, water turns...some color.

Ideas, bees?

ning
(Hive Bee)
10-29-03 19:40
No 467614
      Interesting link

chloro-p-benzoquinone from chloro-p-aminophenol (http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv4p0148)

Interesting, to say the least. Gotta give it to OrgSyn, they always got SOMETHING cool hidden in there.

ning
(Hive Bee)
10-30-03 22:45
No 467876
      Route revised to eliminate chloroacetone

Mind you, ning doesn't mind dealing with potent war gas lachrymators, but ning does mind poor yields and difficult procedures. Apparently once acetone is chlorinated, it becomes easier to chlorinate, sort of like friedel-crafts alkylation on benzene (which is probably why rhodiums benzene->p2p synth has low yields)---it just wants to keep going and going....

So, though ning did not want to, ning did, and fell back to the allyl chloride route. This way, however, ning has a paper describing EXCELLENT yields of allylation, Even of benzene. When it comes in, rhodium might want to add it to the site.

Anyway, here is the revised (short version) of acetaminophen-->DOB/DOC, version 3

Step 1: allylate acetaminophen. Shouldn't need a catalyst, that mama is ACTIVATED! Use K2CO3 to scrub HCl to prevent it from reacting with allyl. Unless we want that.

Step 2: hydrolyze allyl to a P2P-ol sort of thing (pictures would really help here...). This stage will also probably remove the acetyl group from the amino, just in time for...

Step 3: oxidize with MnO2. This will convert the ring to a quinone, AND the alcohol to a ketone, simultaneously. Yay.

Step 4: shake w/ mineral acid of your choice. DOC/DOB-P2P. Yes, it will add across properly, ning has checked up on that.

Step 5: do what beez do best with ketones...

This one seems much better. The only part ning is shaky on is the hydrolysis of the allyl to an alcohol. Rhodium wouldn't happen to have anything on that, would he? It does seem vaguely related to MDMA or any of those goodies made from plant-extracted funny essential oils.

If that works, this bad boy just went all-otc.

yellium
(I'm Yust a Typo)
10-31-03 08:34
No 467951
      >If that works, this bad boy just went...

>If that works, this bad boy just went all-otc.

How do you get your allylating compound?

hypo
(Hive Addict)
10-31-03 14:19
No 468003
      allylating compound?

simple: glycerol + P + I2 --> allyliodie

n'importe quoi

Antoncho
(Official Hive Translator)
10-31-03 16:02
No 468009
      Details, PLEASE?

Antoncho would dearly like to take a look at those article on allylating (BTW, UTFSE - there's been posted quite an amount of interesting material on this issue on the Hive) and, most importantly, more details on that Hcl addition to the quinone.

If a chem textbook says the rxn happens, it doesn't mean that the yield is acceptable and/or that the reaction is generally practically feasible.

As for the rest of your synth - well, once you begin to practically experiment with your synthetic routes, you'll get a much clearer picture of how the theory relates to practice - that'll change a lot in your views on 'optimal' pathways, i promise wink

But this quinone-to-chloroHQ trick definitely deserves attention, IMHO.

Antoncho

ning
(Hive Bee)
11-03-03 21:11
No 468540
      Hmm..

hypo: read rhodium's page. The RP + I trick is cool, I admit, but ning would like to avoid RP+I for other reasons, namely, it's hot as hell. And if there was an easy source for RP, other bees would be all over it. And perhaps glycerin+oxalic acid-->allyl alcohol+HCl (I know, I was surprised too)-->allyl chloride route is easier than scraping matchbooks and subliming tincture. If there is a lack of info on that part, ning will be sure to post the papers on making of allyl alcohol.

Antocho, ning was going to post that paper 3 days ago, but there was some posting error that wouldn't work. Ning tries again now. Look in "nings papers" thread...let's see if the second is less redundant than the first! smile

ning
(Hive Bee)
11-03-03 21:47
No 468546
      Antocho...

Ning does, in fact, have papers discussing this. It does happen in high yield because quinone is rather an "unhappy" compound, which would like to get its resonance back. So when a nice HCl comes along, it gets added very quickly, taking the double bond off one O and letting the thing change back into a proper aromatic. Further, since the aromatic now has no "free slots", it will not add any more HCl.

Even better, when its a alkylquinone, the HCl adds, for some reason, the Cl (or Br, etc.) always adds PARA to the alkyl substituent. Which is just what we want, for DOC/DOB/2C-X, etc...
alternately, toluquinone+HBr, acetone enolate, DOM-P2P!
it's a great way of sticking halogens on a ring in a controlled way, in nearly quantitative yield, with no gasses!
Other interesting points:
- Cl2/Br2 will dichlorinate/dibrominate quinone to dichlorohydroquinone. Usually para to eachother, if ning remembers correctly.
How about I2? Heh! Who knows?

- You can get the halogen meta to the alkyl substituent (2,5-dihydroxy 3-halo phenyl....)if you use ZnCl2 or some such thing. Ning has a paper where they did both. So there is quite some flexibility here. Oxidize aspirin to catechol, and then even more becomes possible.

And by the way, ning doesn't know if all the bees know, but alcohols can be added to quinones too, just like HX, HOblahblah will add blahblahO-hydroquinone. Only thing is, apparently in that case the quinone is stronger than the hydroquinone, so it will re-oxidize it to a quinone. Perhaps the way around this is to dribble slowly the quinone into a large excess of the alcohol that is well stirred, like an acid dilution, so the chances of the quinone meeting hydroquinone are small.
Quinones are really magic!
That's why ning says quinones are the future!

Ning is proud of the alkylation step. Ning likes the new route better, although ning would still like the simplicity of the chloroacetone method. Using the amino group to activate the ring and make the alkylation easier before throwing it away seemed like a cool idea to ning at the time.

Also, there is the simultaneous oxidation of the aminophenol to quinone and the alcohol to ketone. Ning is proud of that one. More proud if it actually comes to ning in a dream of course. But then, ning is not the only dreamer here, right?
Some people's imaginations are no doubt much better equipped than ning's.

So, with toluquinone and X2/HX, we can get...

2,5-dihydroxy 3-halotoluene
2,5-dihydroxy 4-halotoluene

with quinone we can get

2-halohydroquinone
2,6-dihalohydroquinone
2,5-dihalohydroquinone

Ning has no idea what catechol could become.

Ning will post the papers of interest or their references ASAP. Ning really did think that the HCl addition was common knowledge. Is it really not in the textbooks?

ning
(Hive Bee)
11-04-03 19:23
No 468735
      Re: HX addition to quinones
(Rated as: excellent)

Antocho & others: Just looked in the chem books...the HCl addition to quinone can be seen in:

Vollhardt & Schore 3rd, pp. 1010
Norman & Coxon Principles of Org. Synth. 3rd, pp. 607

Look for the synthesis of "Chloranil", it is 2,3,5,6 tetrachloroquinone. It is made by mixing quinone with HCl and perchloric acid. The HCl adds and changes it to hydroquinone, the perchloric acid oxidizes it back to quinone, the HCl adds, .... until there's no more slots left. Interesting :->

Sad that McMurry, etc. didn't have it. Well they suck. The aforementioned old "properties of organic compounds" book of course had all of that in black and white, but ning is learning to expect that from that funny old book.

Here's some papers with more hard data to chew on:

J. Chem. Soc. Perkin II, 1983, pg.271
"The Kinetics and Mechanisms of Additions to Olefinic Substances. Part 16. Addition of Halogens to 1,4-Benzoquinone and to 1,4-Napthoquinone, and Dehydrohalogenation of the Resulting Adducts"

They talk about mechanism, and adding Cl2, Br2 and ClBr to quinones. Ning can't quite understand all the mechanism talk, but maybe other interested bees can.

J. Chem. Soc 1959 pg.3254 "Muscarufin. Part II. 2-(4-Carboxybuta-1,3-dienyl)-1,4-benzoquinones"

The shit! They exactly take a alkyl 2,5 benzoquinone and convert it to 4-chloro-2,5-dihydroxy alkene with HCl.
--SNIP--
On treatment with hydrogen chloride in chloroform, 2-(4-carboxybuta-1,3-dienyl)-1,4-benzoquinone gave 2-(4-carboxybuta-1,3-dienyl)-5-chloroquinol, identical with the product of the Elbs oxidation of 5-(4-chloro-2-hydroxyphenyl)-2,4-pentadienoic acid.
--SNIP--
(iii)2-(4-carboxybuta-1,3-dienyl)-1,4-benzoquinone (1.2 g.) was suspended in chloroform and hydrogen chloride was bubbled through the mixture for 5 min. After 10 hr. the precipitated 5-(4-chloro-2-hydroxyphenyl)-penta-2,4-dienoic acid was filtered off, and recrystallized from acetic acid to give yellow needles (1.05 g.), m.p. and mixed m.p. 254 C. Oxidation with ferric chloride, (another trick, folks!) as described previously, gave the quinone as orange needles (0.57 g.)(from alcohol), m.p. 188 C.
--SNIP--

This is almost exactly what ning needs for the DOC/DOB synth. Ning is willing to bet most of yield loss was in recrystallization, too. And that aqueous (or methanolic) HCl can do the job as well or better than that nasty bubbled stuff. But anyway, on to the next item, please...

J. Chem. Soc. 1952, pg. 755 "Acylation Reactions Catalyzed by Strong Acids. Part VI. A Comparison of Zinc Chloride and Perchloric Acid as Catalysts for the Thielle Acetylation of Quinones."
Here they are concerned with attaching acetic anhydride with quinones, but they show how zinc chloride can attach meta to an alkyl, while HCl will attach para to it. Great pic on page 756!

--SNIP--
4-chlorotolu-2:5-quinol m.p. 175 C has been prepared by the addition of hydrogen chloride to (II)(--tolu-2:5-quinone) (Schniier, Ber., 1887, 20, 2285; Clark, J. Amer. Chem. Soc., 1892, 14, 574; Raiford, Amer. Chem, J., 1911, 46, 450)(--ning intents to chase these refs) and its constitution was established by Raiford.
--SNIP (blah blah blah)--
4-chlorotolu-2:5-quinol-
Dry hydrogen chloride was passed slowly into a solution of toluquinone (0.1 g.-mol) in chloroform (100cc) at room temperature (water cooling) (--ooh, it's exothermic) for 1 hour during which solid material separated. After the mixture had been kept for a further hour the solid (--chlorotoluquinol) was filtered off and crystallized first from benzene-ethyl acetate(5:1), then from chloroform-ethyl acetate, giving colorless prisms (0.08g-mol); m.p. 175 C

--SNIP--

So, till those refs are chased down, here's what ning can glean from these papers:

1. the addition is a room temperature, exothermic process
2. it is high yielding (did they just say 80% after two recrystallizations?)
3. it should be dry (damn! we shall see about that...)
4. it adds para to alkyl substituents exclusively or almost exclusively.
5. it is fast. 5 min --> 1 hr, and these are probably not optimized conditions at all.

So there we have it. The elusive ning has provided a little more support for the crackpot DOB from acetaminophen path, and I know all you bees have other secret desires these refs will prove useful for. Have fun!

ning
(Hive Bee)
11-04-03 22:36
No 468790
      Another step covered
(Rated as: excellent)

Ning doesn't know what the buzz at the hive is about making phenyl-2-propanols from allyl compounds, but as it is an important step in the revised acetaminophen synth, ning found some old papers with some information on just that.

Theoretically, it should be easy--just hydrate the allyl, and there's your alcohol. The literature gives two general ways to do this--the first involves concentrated sulphuric acid at high temperatures to actually sulphonate the allyl, followed by hydrolysis; the second is a simple acid (or base?) catalyzed addition done cold (0-10 degrees).
While ning's books have info on this (a reversible reaction, by the way), ning isn't near the books, so these papers will have to do:

J.Chem.Soc(?), 1935, pg 684 (questionable, sorry)
"Influence of Poles and Polar Linkings on Tautomerism in the Simple Three-carbon System. Part III. Experiments with Benzyl-delta^a- and delta^b-propenylsulphones."

They allylate benzyl sulphinate with allyl bromide, then change the allyl to an alcohol. Here:

--SNIP--
The substances were unchanged when boiled with water, methyl alcohol, or pyridine. The addition of alkali hydroxide or alkoxide was rapid and led to the formation of b-substituted propylsulphones:

R=Ph,Me L=H or Alkyl
R.SO2.CH2.CH=CH2 or R.SO2.CH=CH.CH3 + NaOL ---> R.SO2.CH2.CH(OL).CH3

(ning assumes they didn't use alkoxide with water, of cours :->)

When, by using suitable concentrations of alkali hydroxide or alkoxide, addition was incomplete, no unsaturated sulphone other than the initial compound was found. The formation of a b-substituted addition compound from either of the sulphones did not appear to follow an isomeric change, since each of them yielded the same benzyl-b-iodopropylsulphone when boiled with concentrated hydriodic acid. (--ning thinks, yeah, sure...) Analogous cases of addition are provided by divinylsulphone, which when treated with sodium hydroxide, yields bb'-dihydroxydiethylsulphone (Kretov, J. Russ. Phys. Chem. Soc., 1930, 62, 1; compare also Cashmore, J., 1923, 123, 738), and by a and b-napthyl-deltab-propenylsulphones, which yield the corresponding b-hydroxy-derivatives (Troegar and Artmann; J. pr. Chem., 1896, 53, 484).
--SNIP--(blah blah they can be hydrolyzed apart blah blah)
Action of sodium carbonate solution:
(i) When either of the unsaturated sulphones was boiled under reflux with ?N-sodium carbonate (they left it out!) for 2 hours, a mixture of hydroxy and unchanged sulphone was obtained. Neither the other isomeride nor benzylmethylsulphone could be detected.
(ii) In order to discover whether there was any difference in the rates of conversion of the unsaturated sulphones into the hydroxy-sulphone, each of the former (0.5g) was boiled under reflux with 0.1N-sodium carbonate (25 cc) for 40 minutes. The product, extracted and dried (CaCl2) in chloroform and recovered, had m.p. 84.0 C (for delta-b) corresponding to a 76% conversion, and 86.5 C (for delta-a) corresponding to 81% conversion.

--SNIP--

well, there is a whole bunch of crap about how NaOH hydrolyzes the sulphones apart, but ning thinks to just ignore that for now. Interestingly, Na2CO3 works to hydrate the allyl--there could be something of interest here for the E people? More gentle conditions? Ning also bets that if they kept boiling for another 20 minutes, yield would be almost quantitative.

Next up:
ummm....gotta start writing those journal titles ON THE PAPERS...uhhh...lets say its..
JACS 1934, vol 56, pg.1968
"Synthesis of 5-b-Hydroxypropylbarbituric Acids"
Hey, the wheel turns around, from drugs to other drugs...cool, huh?

--SNIP--
The resistance of the ring in 5,5-ethylisopropylbarbituric acid to the action of sulphuric acid in the cold, prompted the author to study the effect of this reagent on 5,5-alkyl allyl substituted[b] barbituric acids in order to [b]introduce a hydroxyl group in the side chain.
The particular allyl compounds studied were 5,5-allylisopropyl and 5,5-allylisobutylbarbituric acids.
The addition of sulfuric acid to the allyl group takes place very rapidly and smoothly. It has been assumed that the addition of sulfuric acid follows Markownikoff's rule. This method would appear to be applicable to any 5,5-allylalkylbarbituric acid.
The hydroxy compound (I) obtained from 5,5-allylisopropylbarbituric acid was benzoylated to yield the product (II).
In order to show that the benzoyl group was introduced in the side chain, compound (II) was allylated in the 1,3 positions according to the method described in british patent 391,741. (--anyone know what this is??)

Experimental part:

Prep. of 5-isopropyl-5-(B-hydroxypropyl)-barbituric acid (I)
50 g of 5,5-allylisopropylbarbituric acid was added slowly with stirring to 100 cc of sulfuric acid (sp.grav. 1.84) and allowed to stand at room temperature for 8 hours. The solution was poured with constant stirring over 500 g of ice. The precipitate was then filtered and washed with cold water until the filtrate was neutral to congo paper. The product was recrystallized from alcohol. It is soluble in ethyl and methyl alcohols, but it is insoluble in water, ether, chloroform, acetone, or ethyl acetate; m.p. 221-222 C (uncorr.) yield 95%

Prep. of 5-isobutyl-5-(b-hydroxypropyl)-barbituric acid:
Repeated above procedure using 14 g. of 5,5-allylisobutylbarbituric acid, 50 cc of sulfuric acid, and 250 g of ice. The product is soluble in ethyl and methyl alcohols, but it is insoluble in water, ether, chloroform, acetone, or ethyl acetate; m.p. 216-217 C; yield 95%

Cold concentrated sulfuric acid has no action on 5,5-ethylisopropylbarbituric acid.

(AND, the allylation part...)

Diallylation of (II) - 11.1 grams of (II) was treated with 8.1 g of allyl bromide in the presence of finely divided copper and 10% sodium hydroxide according to the method described in british patent 391,741. The product obtained was a very heavy oil which was purified by vacuum distillation, b.p.(25mm) 260 C.

Summary: two 5-alkyl-5-b-hydroxypropylbarbituric acids have been prepared from the corresponding 5-alkyl-5-allylbarbituric acids by addition of sulfuric acid at the double bond and subsequent hydrolysis.

Well, how about that? The yields are nothing to sneeze at, although the conditions seem a *little* rough for some compounds. Luckily, ning's synth needs a soak in sulfuric acid anyway, so perhaps this step and the following MnO2 oxidation could be done in one pot. Ning certainly hopes yields would be as good in the real world.

J. Chem. Soc 1947, pg. 124
"The sulphonation of some derivatives of eugenol"

believe it or not, they were trying to get antibacterial behavior out of these. Wonder if they ever ate any themselves and decided not to report it?

--SNIP--
Treatment of eugenol with concentrated sulphuric acid at 0 C gave largely sulphonated polymers. When O-methyleugenol, however, was sulphonated by stirring with sulphuric acid at 0 C and the sulphonic acids were extracted with water, an amorphous mass was left, from which a 5% yield of the sulfone was isolated.

Hmm...not good. There's your answer for the whole E thing...suphonated polymers. But anyway, ning will try to find more refs on the whole direct hydration thing, while remarking that the indirect (sulphonate->hydrolyze) method, while harsh, seems to give not-too-shabby yields for tougher rings. Also, note that the barbituric acid should have had some steric effects from the other attached alkyl group. Perhaps 4 hours is more than enough for a single allyl group?

So anyway, one pot would be like this, eh?

To 40 mL cold sulfuric acid with stirring is added 10 grams of 2-amino-5-hydroxy-phenyl-2-propene. The mixture is allowed to stand for 4 hours, then is added slowly to 100 mL cold water and stirred for 1 hour. 40 grams of MnO2 (washed battery gunk) are then added, and the mixture heated to 60 C and stirred for 2 hours. The mixture is then cooled and extracted with nonpolar solvent (toluene).
? grams of p-benzoquinone-propan-2-one.

The toluene extract is placed in a beaker with 30 ml aqueous HCl/HBr and stirred at room temp. for 2 hours, then 100ml water is added, the solution basified with Na2CO3 and the toluene removed.

? grams 2,5 dihydroxy 4-chloro/bromo phenyl-2-propanone

The solution with water is boiled dry and 20 g dimethyl oxalate is added. Flask is fitted with reflux condensor/stink pipe and temperature is increased to 150 degrees. After 4 hours the mixture is allowed to cool to 50 degrees and toluene added. After cooling is complete, the toluene is removed and evaporated.

? grams 2,5 dimethoxy 4-halo-phenyl-2-propanone.

So there's your ketone. Whatcha gonna do with it?

Naturally, all the aforementioned was a mere seat of the pants guess, but hey, who knows? The road seems wide open.

Rhodium
(Chief Bee)
11-05-03 02:25
No 468823
User Picture       The not-MDP2Pol synthesis!

J. Chem. Soc 1947, pg. 124
"The sulphonation of some derivatives of eugenol"

Treatment of eugenol with concentrated sulphuric acid at 0 C gave largely sulphonated polymers. When O-methyleugenol, however, was sulphonated by stirring with sulphuric acid at 0 C and the sulphonic acids were extracted with water, an amorphous mass was left, from which a 5% yield of the sulfone was isolated.

Wow! You are the first to find a reference which describes this non-workable preparation of Phenyl-2-propanols from oxygenated allylbenzenes...

Here is my collection of related references: https://www.rhodium.ws/pdf/mdp2pol/

ning
(Hive Bee)
11-05-03 16:22
No 468938
      yeah, that MD ring...

just can't take much abuse, can it? Just found a bunch of kick ass papers on oxidation of alcohols to ketones.
Do you have the one where they use TCCA and acetone to make p2p?

Rhodium
(Chief Bee)
11-05-03 16:47
No 468948
User Picture       MD

yeah, that MD ring just can't take much abuse, can it?

It's sensitive to a lot of conditions, but the aromatic ring is also very activated by having two oxygens and one alkyl chain attached to it, so a lot of things may add to the 6-position. See for example Post 280053 (Rhodium: "Why the Ritter Reaction Fails for Safrole", Chemistry Discourse)

Just found a bunch of kick ass papers on oxidation of alcohols to ketones. Do you have the one where they use TCCA and acetone to make p2p?

UTFSE on the volume/starting page/year for the article in question, and see if it has been posted before.

ning
(Hive Bee)
11-05-03 17:58
No 468956
      seems to be not...
(Rated as: excellent)

They do several clever things in that paper. I imagine the oxidation works by chlorination, first, then by removal of the HCl group, which would be absorbed by base, neatly removing two hydrogens, and changing a -OH to a =O. If this could work on hydroquinones....well, I get ahead of myself. Anyway, the major competing reaction that lowers yield is chlorination of the ketone. So they put the mixture in an excess of acetone, which is a ketone, so the acetone will compete for the chlorination, saving your precious material and raising yields. Pretty cool, actually.

This paper is cool because they actually do p2p-ol to p2p. No extrapolation needed.

Ning strongly suspects the pyridine could be replaced with Na2CO3 or some such thing as that.

Synthetic communications, 22(11), 1589 (1992)
The oxidation of secondary alcohols to ketones with trichloroisocyanuric acid

Gene A. Hiegel and Malekashtar Nalbandy

Dept. of Chemistry and Biochemistry, California State University, Fullerton, Fullerton, California 92634

ABSTRACT: Secondary alcohols are rapidly oxidized to ketones by a solution of TCCA in acetone.

Ketones are often synthesized by the oxidation of secondary alcohols. We wish to report a fast, simple procedure for the synthesis of ketones from secondary alcohols which is suitable for moderate to large scale reactions. (ning sez: huh huh huh)
   Trichloroisocyanuric acid [1] is a relatively stable and inexpensive reagent which has been used synthetically for the chlorination and oxidation of various types of compounds .(1) Secondary alcohols are rapidly converted into ketones with a solution of 1 in acetone containing pyridine.(2) The ketone products are isolated by extraction after removing the cyanuric acid [2] by filtration and replacing the acetone with ether. The yields and purities for the distilled or recrystallized products are shown in the table.

   R1 R1
\    \
3   CHOH + TCCA + 3 Pyr --->   3 C=O + Cyanuric acid + 3 Pyr.HCl
/    /
   R2 R2

Secondary alcohols are oxidized considerably faster than primary alcohols with TCCA allowing selective oxidation of secondary alcohols in the presence of primary alcohols. Selectivity is shown by the oxidation of 2-ethyl-1,3-hexanediol to 2-ethyl-1-hydroxy-3-hexanone, the last entry in the table; none of the starting diol remained in the distilled product. Selectivity is also shown by a competitive experiment using 3.52 mmol 3-heptanol, 3.55 mmol 1-nonanol, 5.19 mmol pyridine, and 1.66 mmol TCCA. Analysis by GC after a 4-minute reaction time showed that only 2% of the 3-heptanol remained compared to 88% of the 1-nonanol.
   During the oxidation of secondary alcohols, HCl is formed, and HCl reacts with TCCA to give chlorine(3). This does not inhibit the oxidation, but since some of the chlorine escapes from the reaction mixture, the amount of oxidizing agent required to carry a reaction to completion becomes less clear. The addition of a slight excess of pyridine minimizes the formation of chlorine.
   It has been reported that TCCA will chlorinate ketones (1,5), but this unwanted side reaction can be reduced by several methods. The use of acetone as the reaction solvent limits the amount of chlorination of the ketone product.(6) The oxidation also proceeds well in acetonitrile, but a higher ratio of chloro ketone is produced. The oxidation proceeds rapidly without pyridine, but the extent of chlorination is less when pyridine is added. This is presumably because HCl promotes equilibration between the ketone and its enol, and it is the enol which is chlorinated(5). A lower ratio of TCCA to alcohol will give less chlorination because the concentration of TCCA remaining after the oxidation is complete will be less. Quenching the reaction with sodium hydrogen sulfite, which destroys TCCA, as soon as the oxidation is complete will minimize chlorination as well. Since chloro ketones are quite reactive toward nucleophiles, they are normally converted to hydroxy ketones during the sodium hydroxide wash step in the workup and are removed at either the extraction or distillation stage.
   The low cost of TCCA, the speed of the reaction, and the ease of isolation of the products make TCCA the oxidizing agent of choice for the conversion of secondary alcohols to ketones.

Experimental:

   Oxidation of 2-Octanol to 2-Octanone:

The following procedure is typical. In a 500 ml, three-neck, RB flask were placed 7.0 g (54 mmol) 2-octanol, 6.2 ml (77mmol) pyridine, 40 ml acetone, and a stir bar. The flask was fitted with a condensor, dropping funnel, and stopper. In 50 ml acetone was dissolved 5.68 g (24.4 mmol, 73.2 meq) TCCA.(7) While stirring, the solution was added from the dropping funnel over a period of 1.5 min. The mixture was stirred for total of 20 min, then checked for the presence of TCCA using wet iodide-starch test paper. The test was negative (8), so the mixture was vacuum filtered to remove the cyanuric acid, and the filtrate concentrated using a rotary evaporator. Ether, 60 ml, was added and the solution washed with 1 N HCl (2x10 ml), 4 N NaOH (10 ml), and saturated salt solution (15 ml), dried over MgSO4, and vacuum filtered. After removal of the ether, the residue was vacuum distilled through a concentric tube column to give 5.73 g. (47.0 mmol, 83%) of 2-octanone: bp 95.0-97.0 C (42 torr)); 99% pure by GC analysis; the IR and NMR spectra agreed with spectra of the standard.
   The reaction was carried out essentially the same way on a larger scale starting with 50.3 g (386 mmol) 2-octanol, 50.0 ml (620 mmol) pyridine in 250 ml acetone and 49.6 g (213 mmol) TCCA in 400 ml acetone added over a period of 60 min with 15 min additional reaction time. Distillation of the 2-octanone gave 40.6 g (317 mmol, 83%) with a bp of 77.8-80.0 C and a purity of 95% by GC.

The Table:

Oxidation of Secondary alcohols to ketones with TCCA

Alcohol    Ketone    Yield    BP/torr Purity
-----------------------------------------------------------
3-heptanol 3-heptanone    85% 136.2/35   99%
2-octanol    2-octanone 83% 95.0 /42   99%
3-octanol    3-octanone 81% 73.6 /26   99%
cyclohexanol cyclohexanone    68% 58.0 /26   97%
2-me-cyclohexanol   2-me-" 77% 63.8 /24   99%
menthol    menthone 82% 108.2/35   99%
borneol    camphor    86% mp 174.8   99%
1-Ph-ethanol 1-Ph-ethanone    90% 107.0/39   99%
Ph-2-propanol Ph-2-propanone 85% 109.8/25   99%
2-Et-1,3-hexanediol "-1-HO-3-hexanone 72% 123.2/25   95%

Refs:

1. (a) Hiegel, et al, Synth. Comm., 1985, 15,5, 385
   (b) Back et al, Can. J. Chem., 1991, 69,9, 1482
   (c) Walters, et al, J. Org. Chem., 1991, 56, 316

2. A previous report of small scale (0.5 g or less) oxidation of several steroid and two terpene alcohols using TCCA has appeared: Mukawa, F., Nippon Kagaku Zasshi, 1957,78,450; Chem abst., 1959, 53, 5338a. This study was of limited scope and a general oxidation procedure was not developed.

3. Hiegel et al, J. Chem. Ed., 1987, 64, 2, 156

4. Stevens et al, J. Org. Chem., 1980, 45, 2030

5. (a) Radhakrishnamurti et al, Indian J. Chem., 1985, 24A, 300;
   (b) Vasudevan et al, ibid, 304.

6. Acetone is also chlorinated, but the chloro compounds are effectively destroyed during workup.

7. As with other strong oxidizing agents, TCCA should be added to the solvent rather than the solvent being added to TCCA otherwise a violent reaction could occur. An excess of TCCA was used because some is lost due to side reactions, and it has been reported to be about 90% reactive as determined by a thiosulfate titration of the iodine liberated on reaction of TCCA with iodide. See Eaton, Mfg. Chemist and Aerosol News, 1964, 35, 12, 45.

8. If the test had been positive, then saturated NaHSO3 solution would have been added, and the solution stirred for a few minutes and tested again. This procedure would have been repeated until the test was negative.

ning
(Hive Bee)
11-14-03 17:50
No 470877
      Eliminating the MnO2 // bleach chemistry

Ning doesn't know if the other bees have seen these papers, but amongst the other cool bleach oxididation of alcohols to ketones papers, ning found one where they use bleach & a PTC to oxidize hydroquinone to quinone, AS WELL AS OTHER ALCOHOLS TO KETONES. In the revised synth (v.3, was it?), we are oxidizing simultaneously the hydroquinone-p2p-ol to quinone-p2p with MnO2. However, if this paper is true, then perhaps we could ditch the battery gunk from the synth altogether, and just use bleach. Ning knows that for large scale synthesis, this would be a great advantage, and also that the wacker bees who want quinone would like this much better than screwing around with the awful all-staining MnO2/C mixture in batteries. Fine. Actually, ning gets the strong impression that oxidizing aminophenols and hydroquinones is pretty similar. Only problem is, bleach seems to be verrry touchy, with regards to pH. In aqueous solution, it goes through at least three compositional phases with different properties, depending on pH:

1: High pH--lots of NaOH in there: OCl- ion.
   This is supposedly one of the stronger oxidizing species, but as it is ionic, it can't travel into a nonpolar solvent phase! (damn!)--this is why most papers on bleach chemistry use PTCs; the PTC will travel into the organic layer and take the ion with it.

2: Middle pH--from 9 to neutral or so(?): HOCl, hypochlorous acid.
   Hypochlorous acid is a weaker oxidizing agent, but it is apparently somewhat soluble in organic solvents. On commercial food processing and pool web pages, they will constantly advise you to adjust pH of water (with HCl) to get most of the chlorine in this form, as it is the most biocidal, despite being a weaker oxidizing agent (perhaps it can cross cell membranes because its oil soluble?)

3: Low pH--Cl2/chlorine,chlorine ion:
Apparently also soluble in organic layer. HOCl + H+ Cl- <--> H2O + Cl2. This is not so different from chlorine gas, and in fact, it will apparently cause chlorine evolution if you carelessly ditch HCl in bleach.

Now, this picture is complicated somewhat by OTHER oxidizing species that can be present.

Most interesting to ning is what happens if you acidify bleach with Acetic acid. The equation changes to:
HOCl + H+ OAc- <--> H2O + ClOAc
The chloroacetate ion is a powerful oxidizer. Also, interestingly, acetic acid is a good solvent for both polar and nonpolar compounds. Ning has a paper describing just such a system, (no PTC necesary), and if the hive doesn't have this paper, ning will post it (must UTFSE first).
Also, this system may have the disadvantage of being at an acid pH. Ning wonders about the effect of using NaOAc instead of HOAc. It would introduce the OAc- ion, all right, but what then?

Also, some of the PTC systems are not using the PTC to carry the hypochlorite ion across the oil-water boundary, but rather, the PTC is actually oxidized by the hypochlorite, then travels across to the compound you want to oxidize, and oxidizes it. (The paper on TEMPO-mediated PTC oxidation). Ning would call this "transfer oxidation". This is not what we want because it seems that this type of system is much more dependent on a specific PTC's characteristics than a simple PTC oxidation system.

Ning wonders what would happen if the nonpolar compound is dissolved in alcohol/water mixture. several of the papers show that bleach can be selective for only secondary alcohols, sparing the alcohol the raging force of its oxidizing power. Whether and how well this can work remains to be seen.

Also, there is the very good possibility of taking advantage of the hypochlorite ion's difficulty in crossing solvent layers, particularly in the case of making quinone from hydroquinone. Hydroquinone is fairly soluble in water, while quinone is not, so if toluene and bleach are put together, and hydroquinone is added, either as sodium salt, or just as-is, then as the hydroquinone is oxidized to quinone, it will automatically get sucked across into the toluene layer, and be thus protected from further oxidation, or undesired chlorination. Just pour off the toluene when the reaction is done, and it contains your quinone, to do with as you please.

The only annoying thing about this whole thing is that while both the secondary alcohol to ketone, and hydroquinone to quinone reaction have been done with bleach in high yield, they are done under various conditions that make it hard to tell what is really necesary, and what is not.

Ning's reccomendation to the hive community with a strong hankerin' for OTC quinone and a little lab equipment is to do this:

Get some tylenol or whatever. Also, get some hydroquinone.

Bleach is naturally basic, so if ning's guess about the OCl- ion being good enough for this oxidation is correct, you needn't adjust its pH. Just use as is.

Now do these experiments:

1. bleach & hydroquinone. Toluene top layer. No PTC.
2. bleach & tylenol. " "
3. bleach & hydroquinone. Toluene top layer. Add vinegar.
4. bleach & tylenol. "

evaporate the toluene, report your yields. hydroquinone is very yellow. all the (minimal) gak in the acetaminophen pill should stay in the water/bleach layer.
If yields from tylenol suck, but yields from hydroquinone are good, then the next thing to do is split off the aceto group from the amino. Ning is hoping that the oxidation will do that, but it is possible not.

To do that, just put the tylenol in fairly strong acid or basic solution and give it a little boil. In the microwave should work. If you are adding acetic acid, well, how about that...?

then do:

5: p-aminophenol + bleach
6: p-aminophenol + bleach + vinegar

Ning assumes a 2-molar excess of hypochlorite will be sufficient. Any bee got time for this?

Bleach chemistry is more complicated than it looks, eh?
But that is part of it's power--by screwing around with the ions in bleach, you can make in oxidize, hypohalogenate, chlorinate, epoxidize, oxidize only secondary alcohols, oxidize both primary and secondary alcohols, etc, etc. Very versatile reagent.

pericles
(Newbee)
11-15-03 03:27
No 470973
      Some info

Sorry for the poor quality of the response, I'm quite far from my equipment and so can't provide much. I figure something is better than nothing, though.

0 min - 500mg powdered acetaminophen was added to 250ml bleach. Acetaminophen quickly turned dark orange / brown and sunk to bottom.
+5 min - White bubbles begin appearing on suface of bleach.
+7 min - The aforementioned orange / brown powder begins rising to the surface of the bleach.
+10 min - Out of concern the reaction was going too far I filter off the bleach. Bleach was noticably warm to the touch.

Filter paper has a light brown / tan coloured substance on it in addition to a white substance (tan to white ratio is around 2/3). Tan substance not easily soluable in water, isopropyl alcohol or weak acetic acid. White substance no soluable in water, others unknown.

Polverone
(Hive Bee)
11-15-03 11:15
No 471025
      chloroacetate from TCCA?

Most interesting to ning is what happens if you acidify bleach with Acetic acid. The equation changes to:
HOCl + H+ OAc- <--> H2O + ClOAc
The chloroacetate ion is a powerful oxidizer. Also, interestingly, acetic acid is a good solvent for both polar and nonpolar compounds. Ning has a paper describing just such a system, (no PTC necesary), and if the hive doesn't have this paper, ning will post it (must UTFSE first).
Also, this system may have the disadvantage of being at an acid pH. Ning wonders about the effect of using NaOAc instead of HOAc. It would introduce the OAc- ion, all right, but what then?

Again you intrigue me. I didn't realize that chloroacetate was a good oxidizer. Chloroacetic acid has interesting uses in its own right. Do you think that one could produce significant amounts of sodium chloroacetate and TCCA in solution? That would make me as happy as a clam.

I tried dissolving some TCCA in glacial acetic acid tonight. It didn't dissolve very well. It does dissolve nicely in acetone though.

Oh, and I'm also interested in the possible conversion of primary alcohols to aldehydes with TCCA. Unfortunately, everything I've seen about that has used the exotic catalyst TEMPO to make it work.

19th century digital boy

Rhodium
(Chief Bee)
11-15-03 15:00
No 471041
User Picture       acetyl hypochlorite, not chloroacetate

He is not talking about chloroacetate, Cl-CH₂COO^-, but rather acetyl hypochlorite, CH₃COOCl, he just failed to use the correct nomenclature (after all, the type of compound is pretty uncommon).

ning
(Hive Bee)
11-17-03 00:16
No 471284
      primary alcohols to aldehydes....

Well, ning might have seen the paper you saw...yes, it was an indirect oxidation. Uhh...well....good catch, rhodium...
Ning thinks bleach has a better chance to do the dirty aldehyde deed, and if ning can find that paper...it used a PTC, if memory serves, but it wasn't tempo...one of the more common quats, methinks.
If anybee can say something definitive about the oxidizing/selectivity of the different species in bleach at various pH, ning would be very happy to hear about it.

If it is of interest to the hive, ning copied something on NaOCl from "encyclopedia of reagents for organic synthesis" or something like it, it has a lot of refs.

Ning doesn't really like MnO2 as much as bleach, but it is fairly cheap, OTC, and can make aldehydes.

by the way, 40 g MnO2 from batteries lost almost 10 g after being washed with 2 liters warm water and dried. This must be the infamous electrolytes. Beware, all who would use the MnO2...wash it first. Unfortunately, ning has not yet devised a way to figure out how much carbon is in there.

pericles--great! ning likes this! Other experimentation!
There are several possibilities.
1. you got benzoquinone, with oxidized gak
2. you got partially oxidized something (like N=<=>=O)
3. you got trashed bits of acetaminophen, or chlorinated crap

Hopefully the first one :->
In ning's experience, orange/brown/black is the progression taken when the stuff is left to sit overnight after the MnO2 treatment. Try extracting with toluene. If it turns yellow, well.........that's the color of gold, isn't it?
Evaporate off solvent and smell. Supposed to be "pungent".
Wonder what they say phosgene smells like?

It may be necesary to hydrolyze the acetaminophen first, but ning suspects the strongly basic bleach may take care of that for you.

Any words, rhodium? Ning is bee shooting in the dark on this topic. Especially regarding the bleach....

life is incomplete...but then, Goedel said it would be...

ning
(Hive Bee)
11-17-03 18:13
No 471402
      PTC Catalyzed Hypochlorite Alcohol Oxidation
(Rated as: excellent)

Hey polverone.... ...ask, and thou shalt recieve...

Phase Transfer Catalyzed Oxidation of Alcohols with Sodium Hypochlorite
Gholam A. Mirafzal & Albena M. Lozeva
Tetrahedron Letters 39, 7263-7266 (1998)

Abstract: Phase transfer catalyzed oxidation of alcohols with sodium hypochlorite in ethyl acetate media resulted in good to excellent yield of oxidized products. These reactions are mild, efficient, and safe. The experimental procedures and work-ups are very convenient.

   Oxidation is an important type of reaction in organic synthesis and as such is used in most research laboratories. Commonly used oxidants include nitric acid which is dangerous and very corrosive, and salts of manganese or chromium which are highly toxic, mutagenic, cancer suspect agents, environmentally harmful and often messy.(1)
In this paper, we report a safer sodium hypochlorite procedure for the oxidation of alcohols. In addition our experimental procedures and work-ups are easy, the yields of oxidation products are good to excellent, and the reaction time is short. Thus our method is even more attractive than the previously described methods for oxidation of alcohols(1-2). It is hoped that this method will have an immediate application in the way oxidation chemistry reactions, in particular, the oxidation of alcohols are performed.(3)
   Various alcohols (primary, secondary, and benzylic) were subject to sodium hypochlorite oxidation under the mild experimental conditions specified below. In all cases, good to excellent yield of oxidized products were obtained.

R NaOCl/R4N+Br-, RT R
\    EtOAc/H2O    \
   C-OH    --------------------> C=O
/    /
R' R'

R = Alkyl Group, R' = H
R = R' = Alkyl Groups
R = Aryl Group, R' = H
R = R' = Aryl Groups

The products were analyzed by IR, and GC-MS techniques. The absence of the alcohol OH stretch, and the appearence of new carbonyl (C=O) stretching for the oxidized products were an indication of the products' identity and the GC-MS analysis provided the molar mass and confirmed the purity of the products. Reactions were all done in ethyl acetate as the organic phase with tetrabutylammonium bromide as the phase transfer catalyst.(4) The oxidation reaction is essentially complete in 30 minutes, and the yields ranged from 72% for the oxidation of cholesterol to 93% for the oxidation of benzyl alcohol. It is essential that fresh bleach be used in order to minimize the amounts of impurities, and maximize yields of the oxidized products.(5)(for that spring fresh scent that just won't give up...) Table 1 summarizes our results for the oxidation of primary, secondary, and benzylic alcohols.(6-7)

(please forgive ning's poor chemical naming...)

Table I. Phase transfer catalyzed oxidation of alcohols with NaOCl (bleach)

1-octanol ---> 1-octanone 86%
2-phenylethanol ---> 2-phenylethanone 73%
2-octanol ---> 2-octanone 92%
cholesterol ---> cholesterone 72%
benzyl alcohol ---> benzaldehyde    93%
9-fluorenol ---> 9-fluorenone 92%
benzhydrol    ---> diphenylmethylketone 80%

NaOCl, EtOAc:H2O, R4N+Br-, Room temp., 30 min.

We have shown that phase transfer catalyzed oxidation of primary, secondary, and benzylic alcohols with sodium hypochlorite results in good to excellent yields of the desired oxidation products. This method of oxidation is mild, efficient, and safe. The experimental procedures and work-ups are very convenient.(7) In addition, the low cost and availability of sodium hypochlorite as commercial household bleach makes this method of oxidation of alcohols very attractive.

Refs & Notes

(1.) TL 1968, 3363; TL 1975, 2647; TL 1979, 399; Synth. 1980, 223; TL 1985, 1699; JCS-perkin 2 1979, 788; Synth. 1979, 134; Vogel's 5th, 668; TL 1998, 3815.

(2.) TL 1982, 4647; This article reported successful oxidation of sec. alcohols using NaOCl in AcOH. However, this method is not effective for oxidation of pri. alcohols and alcohols containing double bonds. It is reported that oxidation of prim. alcohols leads to dimeric esters under the acidic condition described. (in good yields, too!) For instance, oxidation of 1-decanol leads to decyl decanoate as the major product. Also oxidation of alcohols contg. double bonds is reported to produce chlorine-contg. products. Reaction times are long, they typically require 4-6 hours for completion. In addition, reagents used are potentially dangerous. Glacial acetic acid is corrosive and causes burns (so does bleach...); the vapor is extremely irritating to mucous membranes and the upper respiratory tract, and a sodium hypochlorite solution in glacial acetic acid emits chlorine gas, which is a respiratory and eye irritant. (yeah, let's just drink your bleach concoction, eh, mr. man? These academic pissing contests disgust me. I thought science was about escaping darwinistic win/lose mode of living?) We believe our method of phase transfer catalyzed oxidation of alcohol in ethyl acetate is superior over this both in terms of its application and safety consideration.(and we will duel with any who disagree...pistols at 10 paces)

(3.) This paper was presented in the Div. Chem. Ed. at the 213th ACS Nat. Mtg. in San Francisco, CA, April 13-17, 1997 (abstract #100).

(4.) In absence of PTC, little or no reaction is evident, and the alcohol is recovered unchanged.

(5.) Other commercial bleaches work as effectively when used fresh. For precise work, samples may be titrated according to the proceedure of Kolthoff, I.M.; Belcher, R. Volumetric Analysis, Interscience: New York, 1957, P. 262.

(6.) Materials & Methods: 1-octanol, 2-phenylethanol, 2-octanol, cholesterol, benzyl alcohol, 9-fluorenol, benzhydrol, tetrabutylammonium bromide, ethyl acetate, dichloromethane were all purchased from Aldrich and were used as such without further purification. TLC was performed on Eastman Kodak TLC plates (coated film, #13179) with a fluorescence indicator. Commercial chlorox fresh scent bleach (5.25% NaOCl) was used. FT-IR were performed neat or as solutions in dichloromethane on a Nicolet 510P Spectrometer. The low resolution mass spectra (LRMS) were obtained on a HP 5970 GC-MS spectrometer equipped with an HP-1 cross-linked methyl silicone gum (12m x 0.2mm x.33mm film thickness) capillary column. The inital column temp. of 60 C (1 min) then 10 C/min increments up to 250 C (15 min) were used.

(7.) General procedure:
In a 50 ml RBF equipped with magnetic stir bar, 5.56 mmol of the alcohol and 15 ml of EtOAc were mixed. The solution was vigorously stirred at room temp, and while stirring, 15 ml of commercially available Clorox Fresh Scent Bleach (5.25% NaOCl), and 0.3 g (0.93 mmol) PTC Bu4N+Br- were added. The progress of reactions was monitored by TLC using hexane:EtOAc (8:2 v/v) as the mobile phase. Oxidation reactions were essentially complete in 30 min., but in some cases the reactions were allowed to stir for a period of 1 h to insure the complete oxidation process. The organic phase was removed and the aq. layer extracted with 20 ml EtOAc or Et2O. The combined organic layer was then washed once with 20 ml of water, and then dried over MgSO4. After removal of drying agent by filtration, and removal of the volatile materials under reduced pressure, the percent yield were calculated. The GC-MS and IR analysis of the products were conducted in dichloromethane solvent. Both confirmed that the products were pure and contained no starting materials.

blah blah blah

Microscale oxidation reactions using 0.556 mmol of the appropriate alcohol, 1.5 ml of EtOAc, 1.5 ml of bleach, and 0.03 g (0.093 mmol) of PTC produced a similar yield of products but in a shorter period of time, about 20 minutes.

Look for more soon!

ning
(Hive Bee)
11-17-03 19:55
No 471414
      Why ning thinks bleach can make quinones....
(Rated as: excellent)

J. Chem. Research(S), 1999 pg. 672

Sodium Hypochlorite/Dowex 1x8-200: An Effective Oxidant for the Oxidation of Aromatic Amines to Quinones

Mohammed. M. Hashemi & Yousef A. Beni

Polymer-supported hypochlorite ion is a useful oxidant for the oxidation of aromatic amines to the corresponding quinones.

Organic reactions on supported reagents have recieved recently considerable attention from synthetic chemists because of their high efficiency, environmental safety and convenient work-up procedures. (1-3) Polymer supported reagents have emerged as a complementary approach to solid phase organic synthesis. (4,5) Reagents supported on insoluble polymers are particularly convenient for solving many problems in organic chemistry. (6-8)
   Sodium hypochlorite is a readily available and inexpensive oxidant and has been used for the oxidation of variety of compounds.(9) Unfortunately, the traditional NaClO oxidation methods such as oxidation under phase-transfer catalyst have been developed. (10,11) However these methods possess disadvantages, e.g., long reaction times, high temperatures and use of expensive polar aprotic solvents.
   We have now found that it is possible to obtain in a simple way a polymer supported ClO- reagent for the oxidation of aromatic amines to quinones utilizing a commercial anion exchanger resin.
   Oxidation of aromatic amines to quinones is an important reaction in organic chemistry and a variety of oxidizing reagents such as potassium dichromate,(12) potassium nitrosodisulfonate,(13 ferric chloride,(14) sodium nitrate,(15) silver oxide and lead dioxide,(16) lead tetraacetate(17) and hydrogen peroxide(18) have been developed. Most of the reported reagents require vigorous conditions, (12,13,15) some require tedious workup, (17) give low yields (15,16) or long reaction times. (14,19)
We report here the use of hypochlorite ion on Dowex 1X8-200 as an inexpensive alternative for oxidation of aromatic amines with total selectivity to the corresponding quinonones. Table I lists a variety of aromatic amines oxidized with supported ClO- on Dowex 1X8-200 anion exchanger resin to the corresponding quinones.

Table I Oxidation of aromatic amines to quinones

R-C6H4-NH2 ---> R-(O=C6H3=O)

*bzq = benzoquinone, npq = napthoquinone, DME = 1,2-dimethoxyethane
   g resin
Amine Product /mmol   solv. time yield
--------------- ------------   ------ ---- ----- ----
Aniline    1,4-bzq 1.5 THF    30 88%
2-Toluidine    2-Me-5-bzq    2 THF    30 93%
3-Cl-aniline 2-Cl-1,4-bzq   1.8 THF    45 85%
1,2-phenylenediamine 1,2-bzq 2 CH2Cl2 150 95%
2-aminophenol    1,2-bzq 2 EtOAc 150 91%
4-aminophenol    1,4-bzq    2   DME   45 97%
2-toluidine    2-Me-1,4-bzq   1.5 THF    30 95%
1-aminonapthalene    1,4-npq 1.8 DME    45 90%
1-amino-2-napthole 1,2-npq 2 DME 150 89%
1-amino-4-napthole 1,4-npq 2 DME    85 93%

Experimental:

All melting points are uncorrected. IR spectra were recorded (KBr) on an FT-IR unicam mattson 1000 spectrophotometer. 1-H NMR spectra were recorded on a Bruker ac-80 (80 Mhz) spectrometer in CDCl3 and chemical shifts are indicated in delta. Chemicals were purchased from Merck, Aldrich and Riedel AG and were used without further purification. All products are known compounds and were identified by their mp, IR, and NMR properties. All yields refer to isolated products.

Preparation of ClO- supported on an anion exchanger resin:
To prepare the reagent, 55g of the chloride form of Dowex 1X8-200, a macroreticular anion exchanger resin containing quaternary ammonium group, was added under stirring to a 200 ml solution of 1.85 M NaOCl. Chloride ions were readily displaced and the ClO- form of the resin was qaulitatively(?) obtained in 2 h. The resin was then successively rinsed with water, acetone and absolute ethanol and finally dried in vacuo at 65 C for 5 h. The capacity of the resin was determined by stirring 1.0 g of the resin overnight with 20 ml of 2 M aqueous KOH, filtering off and titrating iodometrically. In the obtained hypochlorite solution, the determined average capacity of the dried resin was 2.2 mmol ClO- per gram of resin.

Oxidation of Aromatic amines into quinones: general proc.

Aromatic amine (2mmol) and the dry ClO- form of the resin (1.5 g) were refluxed in 25 ml of dry THF under vigorous stirring for 30 min, then the reaction mixture was filtered through sintered glass and the filtrate concentrated and worked up with 1 M HCl. Flash chromatography (hexane-EtOAc 8:2 v/v) gave the corresponding quinone.

refs

(1) Synth. 1979, 401; 481
(2) T 1996, 4527
(3) T 1997, 5643
(4) TL 1996, 7193
(5) Synth. 1997, 1217
(6) JACS 1976, 6737
(7) TL 1981, 663
(8) TL 1995, 1359
(9) Oxidation in Organic Chemistry, ACS, DC, 1990
(10) TL 1976, 1641
(11) TL 1998, 1641 (wierd!)
(12) T 1986, 5065
(13) Chem. Ber. 1959, 674
(14) Org. Syn. CV2 430
(15) Org. Syn. CV3 633
(16) Chem. Ber. 1906, 3482
(17) JACS 1950, 4601
(18) JOC 1993, 3633
(19) Handbook of anion determination, Butterworth & Co. Ltd. London, 1979
(20) CRC Handbook of data on organic compounds 1989

----------------DISCUSSION----------------

This is one of those papers that does the impossible, in good yields, with mild, nontoxic reagents under room temperature and pressure. All you need for a catalyst is the philosopher's stone....or so it would seem. I know I can't find dowex anywhere easily, although if I really wanted it, maybe a water softener would have some. But that's not the point.

Look at what they oxidize, to get what! With what!
p-aminophenol to p-benzoquinone with hypochlorite ion
Now, as far as I understand, that "macroreticular anion exchanger resin" is just the same thing as a quaternary ammonium PTC, except it is embedded in plastic instead of free. This naturally makes workup much nicer, but it points us to some important points:

1. It is the ClO- ion which is doing the oxidizing, not the PTC or resin. (no TEMPO-mediated transfer oxidations here)

2. The resin is more or less exchangeable with a PTC

3. The only reason to use a resin or PTC in this case is to get the stupid organic compound to come into the water layer where the hypochlorite ion is.

Now bleach already has plenty of hypochlorite ion in its basic state, so we should concern ourselves with how to get our lovely aminophenol down there to meet it.

Maybe for other compounds this would be a problem, but since p-aminophenol has a phenol group, which can be "salted" with NaOH, which bleach happens to have a lot of in it too. That will ionize it and make it soluble. Maybe the oxidation depends on the phenol not being salted? I don't think so, just look at all the crap they oxidized...aniline worked well too, so I think it probably doesn't matter so much what is attached to the stupid amino group. Also, if there is an acetyl group on the amino, under the basic conditions, its very likely to get hydrolyzed off...sounds pretty easy to me.

So, I wonder if they even bothered to try disolving the p-aminophenol in bleach without all that other trickyness with anion exchangers, etc. Maybe if they did, they wouldn't have so much to write about, eh?

So, acetaminophen in strongly basic bleach, with or without acetone or alcohol cosolvent. 1,2-dimethoxyethane is ethylene glycol dimethyl ether, boiling at 85 C. Ethanol might substitute(bp 78), while acetone boils low (56 C), but has been used in bleach oxidation papers very nicely. Ethyl Acetate would probably be hydrolyzed. Anyway, select your cosolvent, boil and stir for a while. Extract with nonpolar solvent. I would expect the stuff would become a crud or oil and float to the top, as it's not water soluble.
No PTC necesary, thinks I. Nor ion-exchanger resin.

Another piece falls into place. I see no theoretical reason why a simultaneous oxidation of ring and chain couln't happen, yielding the desired 1-(2,5-benzoquinone)-2-propanone, ready for HCl/HBr addition and methylation.

Comments?

Chimimanie
(Hive Bee)
11-18-03 03:15
No 471501
User Picture       quinone, rambling and dowex
(Rated as: excellent)

Good work Ning. smile

Another piece falls into place. I see no theoretical reason why a simultaneous oxidation of ring and chain couln't happen, yielding the desired 1-(2,5-benzoquinone)-2-propanone, ready for HCl/HBr addition and methylation.

I would prefer to have the isopropanol in place of the ketone, as according to Post 358239 (poix: "2,5-dimethoxy-phenylacetone from o-Allylphenol", Novel Discourse) the 1-(1,4-Benzoquinonyl)propan-2-ol rearrange itself to 2,5-dihydroxy-P2P in reasonable yield (70%) by sunlight.

But of course the quinone can be reduced selectively to the hydroquinone while keeping the ketone untouched with Na2S2O4 (hydrosulfite, dithionite) in great yield too.

One question: how would you want to put the side chain on the quinone?

EDIT: now that i have read the whole thread i see what you are aiming at. Personally i would prefer going this type of route from p-methoxyphenol than paracetamol, and halogenate the ring at the end of the synthesis, like usual.

Concerning the chlorination of the alkylated quinone, you may find this article J.Serb.Chem.Soc. 67(8–9)547–551(2002) (http://www.shd.org.yu/HtDocs/SHD/Vol67/No8-9/V67-No8-9-01.pdf) interesting.

One of the viable way I am seeing is by hydrolysis, then oxydative decarboxylation of the acetal of ethyl acetoacetate, if the acetal resist such conditions, to yield the radical of acetone and quench it with benzoquinone with a dash of silver nitrate in the medium, like Post 264250 (halfapint: "Re: alkylation of quinones", Novel Discourse) suggested. But again acetoacetate is not OTC. The (non-posted) mercury acetamidation stay the best way to DOX compounds in OTC fashion IMHO as mercury, propylene, and acetamide are all OTC (or easy to make). (hint: think more about this: Post 426454 (Chimimanie: "Dimethoxy-phenylethyl alcohols", Novel Discourse)) wink

Also yes Dowex are used in all sort of washing machine, like to wash clothes or kitchen plates. The NaCl they add in their shitty two color tablets is used to displace the different ions from the resin to evacuate them and free the resin to catch new ones.

ning
(Hive Bee)
11-18-03 22:30
No 471628
      Hmm...some good shit...

Thats some good info. Ning likes.
Only thing ning wonders, what's wrong with the allylation/claisen rearrangement method? It's OTC, and relatively easy (oxalic acid + glycerine, boil boil boil--->allyl alcohol, add dry HCl, ---> allyl chloride)
Or, if you have iodine and RP handy, one step to allyl iodide.

Then, mix your acetaminophen with the stuff in NaOH, and it should O-allylate. Perform the Claisen rearrangement by heating it real toasty, and it will become an aryl allyl. These two steps can be done in one pot, and ning has 3 or 4 papers discussing the making of allyl alcohol and allyl chloride. If you do it this way, ning thinks it is better to use acetaminophen than hydroquinone, as the acetaminophen can only alkylate in one place (right???), whereas hydroquinone might be tempted to alkylate twice. Also, while ning wanted to directly alkylate in the past, it now seems more efficient to do the O-allylation/claisen rearrangement way. (See rhodium's page, or Orgsyn.org under Eugenol) The rearrangement way has good yield.

And ning can definitely understand the attraction of p-methoxyphenol, but since you still need to methylate it (just once instead of twice), and you need to chlorinated or brominate the ring, which is easier using the quinone modality than otherwise, it seems to ning not to bee much simpler or easier to use p-methoxyphenol than acetaminophen. And where is p-methoxyphenol otc? Ning may have uses for such a thing. But ning hasn't seen it. Ning's dream is psychedelics for the people-- a synthesis of a drug that is so powerful that a kilo can supply a whole city, so OTC that every precursor can be bought off the shelf no questions asked in every supermarket and hardware store, and so easy that your average meth cook or college student could do it. To render the drug war obselete, through chemistry. Or as close to it as possible. That is ning's dream. And plus, since acetaminophen is the usual gak "they" use to poison other drugs with, to use it as the main precursor in such a synth has a touch of divine, poetic justice to it. Since acetaminophen is the gak they use to gak everything else, what will they gak it with? I think I hear the gods laughing quietly...

Those are some good links though. Ning will read, and expand knowledge. Ning's power and focus is devoted to this goal.

A bit of info, for those who are watching with interest: Ning had a fitful night, and dreamt of something....

10 mmole acetaminophen, as powdered tablets.
50 mmole NaOCl as bleach
70 mmole NaOH, for the following purposes:
10 mmol for "salting" with the acetaminophen
10 mmol for hydrolyzing off the acetyl
10 mmol for good measure.
50 mmol just in case the bleach needs it.

The total volume came to about 100 ml.

two runs were performed: one with acetone, one without.

1st run:
The lye was dissolved in the bleach. Nothing happened. The acetaminophen was swirled with the acetone and poured into the bleach. A very vigorous and exothermic reaction followed, with the acetone/acetaminophen mixture turning midnight black immediately. A strange smell emenated from the flask, and there was much boiling. After some time, a yellow bubbly crust formed in the top of the flask.

Worried that the bubbling bespoke of some awful fate for the acetone, (after reading about base-catalyzed haloform reactions....), the dreaming chemist performed another run.

This time, half the lye was dissolved in a small beaker, and the acetaminophen powder poured in. It instantly turned light muddy brown, which ning takes to be the hydrolysis reaction to p-aminophenol. It also dissolved in this form, which was very convenient. This mixture was then dropped into the bleach and stirred. The reaction was again exothermic, and the same midnight brown was observed. A very obnoxious, foul odor evolved from the flask. The bubbling was noticeably less than the last run. The flask was placed outside with a card over it to let it run, and left overnight.

Ning lost the dream here, and after some irrelevent fluff, got it back again.

It was morning, and the chemist took the second run's flask and examined it. There was the same yellow layer on top, although noticeably smaller. When a stirring rod was dipped into the black/brown gunk, it came out with a yellow coating. It would appear that the mix was actually yellow, but too bloody opaque to see.
No, you know what, it looked like this (http://www.uni-regensburg.de/Fakultaeten/nat_Fak_IV/Organische_Chemie/Didaktik/Keusch/p15_chinhydr-e.htm)

hmm, how interesting.

The workup is where the dream stopped. It would seem that the chemist was unaware that acid workup is necesary, as quinone is soluble in alkaline soluttion. So after trying to get it into toluene with no success, the chemist dropped sulfuric acid into the mix (now in separatory funnel), and stirrrrred it, succeding only in creating a VICIOUS emulsion. Addition of salt didn't help much. That's where the dream ended. Such a sad thing.

so, bees, could it be a quinhydrone our strange chemist had? how annoying, if that was the case. And the need for the acid workup? Seems like it needs a hydrolysis to finish? More dreaming is in order. Lets see who the sandman visits with his glassware next?

ning
(Hive Bee)
11-18-03 22:46
No 471635
      that serbian paper is nice...

and if you have NaOEt and EtOAc, you can make ethyl acetoacetate,(orgsyn) which ning bets you could hydrolyze to acetoacetic acid. So it is concievably OTC, but if you have NaOEt, you might as well just use the drone enolate synth with acetone...
Mind you, that is one thing ning has been trying to do with that Sodium Oxide crap...So ning is working on it...That EZ-iodation with KNO3, combined with some NaOEt or NaOiPr and acetaminophen also has some good potential.

Ah, well.

Chimimanie
(Hive Bee)
11-19-03 01:47
No 471656
User Picture       Why i prefer p-Meo-phenol?
(Rated as: excellent)

Because it is cheap, OTC, and there is plenty ref on claisen reaction with it. Acetaminophen is an expensive substrate and if you want it OTC you have to extract it from shitty pills, that i will never do. I do not extract pills like the usual meth moron. Its all about proud to bee a bee that do not give away money to Big Pharm's Co whose policies i do not like.

And ning can definitely understand the attraction of p-methoxyphenol, but since you still need to methylate it (just once instead of twice), and you need to chlorinated or brominate the ring, which is easier using the quinone modality than otherwise, it seems to ning not to bee much simpler or easier to use p-methoxyphenol than acetaminophen. And where is p-methoxyphenol otc? Ning may have uses for such a thing. But ning hasn't seen it.

-To methylate once instead of twice is cheaper.

-Bromination of the ring is a breath from DMA, if DOB is your target you should not care about legality. For the chlorination i think too the quinone as some good potential, but using the quinone only for that is waste of good reactant, you should aim to use the quinone to put a correctly substituted side chain on ring without passing through the two or three steps of allylation, thermal claisen rearrangement and further side chain processing. From quinone those steps could bee reduced to one or two.

-p-methoxyphenol is OTC from hydroquinone following the work of Antoncho, or from cheap and avaiable anise oil following Dakin reaction.

I will give you some refs to chew:

-First: a Claisen on p-Meo-phenol (as well as on sesamol for TMA-2 freaks) from Patent US5977117:

Example 17:

a. Allyl 3,4-(methylenedioxy)phenyl ether:

Allyl bromide (1.75 g., 14 mmol) was added to a solution of sesamol (2.0 g, 14 mmol) that had been dissolved in 50 ml of dry acetone, followed by addition of powdered potassium carbonate (2.4 g, 17 mmol) and the resulting cloudy solution was refluxed for 18 h. The solution was cooled and the solvent removed in vacuo. The remaining suspension was extracted into ether and the organic layer was washed with water (1 x 25 ml), brine solution (1 x 25 ml), and dried over MgSO4. Concentration of solvent yielded 2.4 g (94%) of a pale yellow oil which was used in the next step with no further purification.

b. 2-allyl-4,5-(methylenedioxy)phenol:

A solution of allyl 3,4-(methylenedioxy)phenyl ether (2.4 g, 13 mmol), was dissolved in 30 ml of 1,2-dichlorobenzene and the solution was refluxed for 18 h. The solvent was removed under high vacuum in a water bath set at 60°C. The remaining oil was extracted into ether, washed with brine and dried over MgSO4 The solvent was removed under vacuum to give a yellow oil which was further purified by flash column chromatography. Elution with 10% ethyl acetate/hexanes gave 2.2 g (92%) of the pure compound as a pale yellow oil.

Chimimanie's comment: The 1,2-dichlorobenzene can bee replaced by another high-boiling solvent, or by melten predistilled moth ball (1,4-dichlorobenzene), and workup can bee basic aqueous extraction instead of solvent evaporation.

Example 22:

a. Allyl(4-methoxyphenyl)ether:

Allyl(4-methoxyphenyl)ether was prepared in the same manner as described in Example 17a, but using 4-methoxyphenol (10 g, 84 mmol) and allyl bromide (9.7 g, 84 mmol), in 98% yield as a yellow oil.

b. 2-Allyl-4-methoxyphenol:

2-Allyl-4-methoxyphenol was prepared in the same manner as described in Example 17b, but using allyl(4-methoxyphenyl) ether (13.0 g, 79 mmol). Column chromatography using 10% ethyl acetate-hexanes resulted in 11.6 g (89% yield) of the pure phenol as a pale yellow oil.

also check https://www.rhodium.ws/chemistry/25.meo.allylbenzene.html

and the whole thread here Post 428230 (pHarmacist: "New, promising route to DOX series?", Novel Discourse) with various synthesis of allyl halide posted too.

-You will bee happy i found this patent for a part of your route: Patent WO9320807 check example 1 p 27-28/69:

Preparation of 4-acetamido-2-allyl-phenol:

Commercially available 4-acetamido phenol (1 molar equivalent), allyl bromide (1 molar equivalent) and potassium carbonate (1 molar-equivalent) in butan-2-one were heated at reflux for 18 hours with stirring. The mixture was cooled, filtered and the solid residue washed with ether. The combined filtrates were evaporated and the solid residue was further purified by cristallisation from ethyl acetate-hexane to give 4-acetamido-1-allyloxy benzene as a colourless solid, mp 85-86°C.

The above allyl-ether was heated under reflux in diphenyl ether for 0.16 hours. The cooled reaction mixture was diluted with diethyl ether and then extracted with sodium hydroxide solution (2M). The aqueous extracts were combined and then acidified (10M HCl). The aqueous phase was extracted with ether. After evaporation of the ether, the oily residue was triturated with hexane to give a solid which was further purified by recrystallisation from ethyl acetate-hexane to give 4-acetamido-2-allyl phenol as a colourless solid, mp 82-85°C.

also check JMC 1995 38(21) 4157-60 and JACS 1998 120(12) 2963-2964 maybe the yield will bee given in those refs.

-I didnt found the hydrolyse of the amide to the amine, but i found a preparation of 4-amino-2-allylphenol from sulfanilic acid, sodium nitrite and 2 allyl-phenol in Patent US3723118:

(4-amino-2-allylphenol hydrochloride):

While a solution consisting of 97 g. of sulfanilic acid, 39.2 g. of sodium carbonate monohydrate and 1 liter of water was maintained at 8°C, 168 ml. of concentrated hydrochloric acid and then 40.6 g. of sodium nitrite dissolved in a small amount of water were added to obtain a reaction mixture containing white diazonium salt.

The resulting mixture was added to a solution composed of 112 g. of caustic soda, 164 g. of sodium carbonate monohydrate, 75 g. of 2-allylphenol and 2 liters of water with stirring, wherein the temperature of the reaction mixture should be kept below 5°C in a water bath. After the addition, the water bath was removed and, after stirring for an hour, 400 g. of sodium hydrosulfite was added thereto followed by heating to 70°C to provide precipitated white crystals of the amine. After cooling, the crystalline amine was collected and converted into its hydrochloride, whereby 67 g. of 4-amino-2-allyl-phenol hydrochloride, as colorless crystals having a melting point of from 177 to 190°C (decomposed), was obtained in a yield of 64.4%.

From glycerol/oxalic, nitrobenzene, Tin, sodium nitrite and sulfuric acid all needed precursors can bee made.

The abstract of JACS 1917, 39 2188-224 tell us this:
o-Allylphenol, bp (22) 109-10°, is obtained practically quant, by isomerization of CH2:CHCH2OPh by Claisen's method; with NaOH, NaNO2 and AcOH it gives p-nitroso-o-allylphenol, yellow-brown crystals, m. 99.5-100° (partial decompn.), reduced by NH3H2S to 2-allyl-4-aminophenol, leaflets, m. 112.5-3.5°

check also at the same time JACS 1958, 80 3271-7, and if you understand german, check the old Claisen's article which describe both compounds : Ann. 1919 418 69-120.

- Now speaking about the potential of quinone, i think you should check this ref (I haven't now but it look promising).

Chem. lett. 1992 7 1299

The abstract describe a reaction of monoallyl-oxalic acid ester with quinone and silver/persulfate to yield the allyl quinone (para-to an alkyl group to yield DOM precursor too) in 90%+ yield. I hope it turn to be a good paper.

Otherwise a chinese frown paper (Huaxue Xuebao 1991 49(8) 827-32) say: quinone + allyl-Br + Sn metal in THF/H2O, then FeCl3 give the allylquinone in 48% yield. Various other papers deal with organo-tin compounds, but this one use metallic tin instead of organometallic tin compounds, too bad I cannot understand chinese.

Some refs I didnt check about quinones here:

Helv chim acta 1984 67(5) 1406
Free radical research 2001 35(1) 63
JCS (C) 1966 18 1627
JCS (abstract) 1965 5060

Enjoy the refs, but i will not change my mind, HQ --methylating agent--> 1,4-DMB --Hg2+, acetamide, propylene--> acetyl-DMA --iodination--> acetyl-DOI --basic hydrolysis--> DOI stay unbeaten in my mind.

ning
(Hive Bee)
11-19-03 02:54
No 471661
      welll....

more good stuff...that ref on the claisen with p-aminophenol ester is a good'un.

BUT...dude...you're bent. wink

Acetaminophen is an expensive substrate and if you want it OTC you have to extract it from shitty pills, that i will never do. I do not extract pills like the usual meth moron. Its all about proud to bee a bee that do not give away money to Big Pharm's Co whose policies i do not like.

It's nothing like extracting ephedrine, I promise you. And nowhere near as expensive as you seem to think. I bought 250g for $7, and a 500mg pill weighs 550mg...about 1% gak. Not the most challenging of extractions.

From glycerol/oxalic, nitrobenzene, Tin, sodium nitrite and sulfuric acid all needed precursors can bee made.

ummm...you're kidding, right? NaNO2 is hardly a trivial thing to make, tho' I know it can be done. Tin metal is not that easy to find in bulk either, maybe you have a trick.
And how, in the name of the seven demons, are you going to make nitrobenzene? Easily? From benzene? Halfapint might have liked to hear that trick, for his lignin syringaldehyde work.

And you are trying to imply that all of these things together are cheaper than buying a bottle of pills and crushing them up? Less than 7 bucks for 250g? How much is your time worth??

To methylate once instead of twice is cheaper.

Umm...the methylating agent I am investigating is not the most expensive of things...oxalic acid & methanol, in 1 step. I don't mind if it needs twice the amount. Even if I have to make DMS, it's still not the hardest of things to double the batch size.

Chimimanie's comment: The 1,2-dichlorobenzene can bee replaced by another high-boiling solvent, or by melten predistilled moth ball (1,4-dichlorobenzene), and workup can bee basic aqueous extraction instead of solvent evaporation.

not to bee a nitpicker, but have you ever smelled that stuff? It sublimes at RT, so I don't want to imagine the smell at reflux. Hope you have a stink pipe.

I didnt found the hydrolyse of the amide to the amine, but i found a preparation of 4-amino-2-allylphenol from sulfanilic acid, sodium nitrite and 2 allyl-phenol in Patent US3723118:

Well, thanks...umm...it is just a little heat & stir in NaOH, but anyway...

Thak you for all the hunting & searching you have done, I appreciate it. And if you have all those chemicals, synth away, with my blessings. I especially appreciate the ref on the claisen rearr. w/ p-aminophenol.

Some of those suggestions seem very dubious, tho...lets not complicate things too much here. No NaNO2....

peace cool

Chimimanie
(Hive Bee)
11-19-03 11:03
No 471713
User Picture       Its all about sources

From glycerol/oxalic, nitrobenzene, Tin, sodium nitrite and sulfuric acid all needed precursors can bee made.

ummm...you're kidding, right? NaNO2 is hardly a trivial thing to make, tho' I know it can be done. Tin metal is not that easy to find in bulk either, maybe you have a trick.
And how, in the name of the seven demons, are you going to make nitrobenzene? Easily? From benzene? Halfapint might have liked to hear that trick, for his lignin syringaldehyde work.

All those chems are OTC in my neck of the wood. wink Easier to find in quantities than acetaminophen too, we do not have it at your price OTC here, my nation is less medicated than yours it seems... NaNO2 is a very easy aquisition for me, I will never make it...

Umm...the methylating agent I am investigating is not the most expensive of things...oxalic acid & methanol, in 1 step. I don't mind if it needs twice the amount. Even if I have to make DMS, it's still not the hardest of things to double the batch size.

By the same time you are playing with dimethyloxalate, try to trans-esterify it with allyl alcohol in basic media please.... From the diallyl oxalate, the monoallyl can bee made easily:

Patent JP03223231

Abstract

RO2CCO2M (R = C1-6 linear or branched alkyl, cycloalkyl, alkenyl, cycloalkenyl, benzyl, methoxybenzyl, nitrobenzyl; M = alkali metal), useful as intermediates for antibiotics and allergy inhibitors (no data), are prepd. by hydrolyzing RO2CCO2R using MHCO3. Thus, diallyl oxalate was stirred in aq. KHCO3 at 75-85° for 4 h to give 97.6% monoallyl oxalate K salt in 97.2% selectivity.

not to bee a nitpicker, but have you ever smelled that stuff? It sublimes at RT, so I don't want to imagine the smell at reflux. Hope you have a stink pipe.

Hehe, yes it is a bit toxic too, laugh but other high-boiling solvents are avaiable... BTW have you ever smelled allyl formate? wink

Well, thanks...umm...it is just a little heat & stir in NaOH, but anyway...

After some lab work you will learn to cover your ass with some references, its better time-wise and precursor-wise. wink

Also DMS or acetoacetate are not considered easy things to make in my oppinion.

Now I will devote my time to my ~OTC indigo to AMT synthesis... cool Good luck with your DOX from acetaminophen route. wink

ning
(Hive Bee)
11-19-03 20:35
No 471807
      Your neck of the woods

must not be in america...the most medicated, the least precursors. Or so it would seem...

You have a remarkable patent sourcing ability...but sometimes they don't make sense to me...what could bee done with sodium oxalate allyl ester? Perhaps you're thinking of skipping the allyl-alcohol to allyl chloride step somehow? I don't understand exactly.

I looked up that JACS ref, but it seemed to be on enzymes or something unrelated to quinones. Will look again.

And I say, that hydrolysis is just a hydrolysis! Nothing too fancy about it! Acids or bases, both will do...and you have to go to the right store to get the acetaminophen/paracetemol. You don't go out and buy tylenols, of course. You go to (american) k-mart, or possibly one of the larger supermarkets with a pharmacy. Then you look for the store brand tablets, in a big bottle. Don't accept anything less than 500 tablet bottle of 500mg's, for no more than ~$10US. Acetaminophen is somewhat unique among medicines (although aspirin is similar), because it can basically be made out of coal tar in a few steps, making it more of a "commodity material", and less of a "fine drug". Certainly its synthesis is a lot simpler than, say, pseudoephedrine or something like that.

phenol + HNO3 --> p-nitrophenol ---> p-aminophenol --> acetaminophen
seems like one industrial route. Using gas-phase nitration and hydrogen reduction, its about as easy to make as TNT...maybe p-aminophenol is used in photography because it is a precursor? Or maybe acetaminophen is popular because p-aminophenol is produced in large bulk? hmmm...

Good luck with your...indigo route...ummm...I hope when you say OTC, you mean OTC in my sense of the word too... laugh

----now, for the good stuff---

The easy way to tell if the stoopid acetaminophen has hydrolyzed or not is whether it dissolves in water. It's not very soluble at all. But if you use an acid hydrolysis, both products should be water soluble, and it will dissolve.

Another run was dreamt, this time using sodium dichloroisocyanurate from spa chlorinating agent. Ning realized, while watching this, how useful TCCA is, as it is soluble in organic solvents, while DCCA and NaOCl are not.

The same dark color, the same abomidable smell. A drip of methanol was added, and there were some bubbles. Some soap was added, to no noticeable difference. What the hell?

Ning wonders why it always goes black. Isn't quinone supposed to be pale yellow?

Ning contemplates acquiring dowex....

Anybee have an idea what could be happening?
If there was a wild dreamer with tylenol, bleach, and a spectrophotometer or NMR access, ning would be a happy bee indeed.

ning
(Hive Bee)
11-20-03 22:14
No 472071
      Hydrolysis/Deacetylation of p-aminophenols

Here is another step covered. While the literature is full of information on this kind of reaction (Beilstein gives ~250 hits), hydrolysis seems to be considered a trivial step, not worth documenting or optimizing, so finding good papers is not so easy. Nonetheless, ning, ever-faithful servant of the hive that zee is, managed to dig up a paper covering this critical step of the Ubiquitous Psychedelic Amphetamines Project.

JACS 1948, 1363: Aminoalkylphenols as Antimalarials.
It's a long one, and mostly fluff, so go to page 1372, where you will see This:

4-amino-alpha-diethylamino-o-cresol dihydrochloride (SN 12,458)--
A mixture of 500 g. (2.12 mole) of 4-acetamido-alpha-diethylamino-o-cresol and one liter of 20% HCl was heated at refluxing temperature for an hour. The solution was evaporated under reduced pressure to a thick sirup. A liter of benzene was stirred well into the sirup, and the evaporation repeated using a liter of denatured absolute alcohol. Finally, the sirup was dissolved in two liters of alcohol. The desired salt was then precipitated by the addition of a liter and a half of ether. A total of 541 g. (96% yield) of off-white product was obtained.

blah blah blah, they get good yields for other deacetylations.

Now, ning has many other papers covering deacetylations, but they will bee posted to the tryptamines forum wink

Sick. Sick, sick, sick.

Tengo
(Newbee)
11-21-03 17:28
No 472280
      Does it get any easier than this?

[Edited]

1. Oxidate acetaminophen with hypochlorite in water to N-acetyl-quinoneimine. Easy as hell according to: http://l2.espacenet.com/espacenet/bnsviewer?CY=gb&LG=en&DB=EPD&PN=EP1068177&ID=WO+++9952860A1+I+

2. Acid hydrolysis yields benzo and acetamide

3. Methylate (OTC) with:

   dimethyl oxalate (requires a sulfite-shake BQ -> H2Q)
   H2Q + DMO -> 1,4-DMB (according to ning)

   or

   SnCl2 + MeOH
   BQ + MeOH + SnCl2-> 1,4-DMB

4. 1,4-DMB + Mn(OAc)3 + acetone -> 2,5-dimethoxy-P2P
https://www.rhodium.ws/chemistry/p2p.manganese.html

5. Aminate

DOB!

All OTC, safe and easy...

ning
(Hive Bee)
11-21-03 20:31
No 472308
      Whoa, there tiger!

I like the part about acid hydrolysis, as this may bee the missing step that gives ning black goop time and time again in the hypochlorite oxidation. However, the rest of this route...ning's chem is not good enough to see exactly where you're going...How were you getting that methyl on there? DMO will O-methylate things, but not quinone...and certainly not perform ring methylation, that I know of...Unless you know some sneaky trick...

And what is this...manganese(III)acetate? How does this make a ketone?

That patent's looking kick-ass, though...hmmm...

Put some more flesh on the bones of that route, please, so ning can understand it...

ning
(Hive Bee)
11-21-03 20:46
No 472310
      just found this:

http://www.epsilon-web.net/Ec/materials/

Electrochemical Studies of the Kinetics and Mechanisms of N-Acetyl-p-Quinoneimine Hydrolysis, C.R. Preddy, D.J. Miner, D.A. Meinsma and P.T. Kissinger, 6 (1985) 57-61.

Metabolism of the widely used analgesic acetaminophen (APAP) is thought to involve initial microsomal enzymatic oxidation. The oxidized form, N-acetyl-p-quinoneimine (NAPQI) is readily generated and studied electrochemically. The mechanism of NAPQI hydrolysis is found to proceed by rapid, acid-catalyzed hydration of the imine bond. The resultant carbinolamide undergoes rate-limiting deamidation yielding benzoquinone and acetamide. The pH and temperature dependence of the rate and the mechanism of both steps is studied in detail by double step chronoamperometry. Evidence is presented for catalysis of hydration by HSO4-, suggesting a general alternate pathway. The lifetime and reactivity of the intermediates is discussed with reference to the overdose toxicity of acetaminophen.

Sounds like the man speaks sooth...All ye who crave p-benzoquinone may rejoice in extacy...

Tengo
(Newbee)
11-23-03 03:29
No 472609
      SWIM tried the oxidation in bleach, all a...

SWIM tried the oxidation in bleach, all a mess... midnight black... perhaps the enviroment was too alkaline...?

But what about a neutral or slightly acidic oxidation!
http://electrochem.usask.ca/cc_ep/lab_exp.htm

Take a look at the oxidation-hydrolysis mechanism...
Well hello equimolar amounts of APAP, NaOCl and AcOH!

APAP + NaOCl -> BQ + CH3CONH2 + NaCl

done in AcOH and adding some extra of it towards the end, pushing the equilibrium to the right...

If it works, it's a rather convenient way to BQ and acetamide at the same time...

ning
(Hive Bee)
11-24-03 19:52
No 472912
      Hmmm.....

We seek answers and find only further questions...why are we here? What are we doing? How can we make powerful psychedelics and useful precursors from household chemicals? Ning doesn't know the answers to any of these, this means it must be research!

Many thanks to tengo, for enthusiasm and a useful, though cryptic link. Does any other bee find it entertaining how to do anything, one seems to need to learn how to do everything? To interpret this, ning must now learn cyclic voltammetry. tongue Still, it is a start.

Now, the conceptual issue ning is having trouble with, is how an acid hydrolysis *makes* a quinone in the first part, then the same acid *changes* the quinone to a *hydroquinone* in the second part. Perhaps because the second part is anhydrous??? (ning grasps at straws...) Perhaps somebee understands this seemingly fine distinction better than ning does.

Now, ning is considering typing up that patent tengo found, for all to enjoy, for it is a most enjoyable work. And yet...yet...seems to be missing some important detail (as most patents do), most notably, pH conditions and more importantly, a description of how they manage to dissolve NaOCl in toluene...

For any doubters out there, who want to see p-aminophenol being turned into an imine, one hydrolysis away from their prized p-benzoquinone, read that patent. It is sweet.

Ning did another oxidation test or two, with Na-DCCA again, this time in methanol-h2o, and just h2o. The conditions were neutral, and a slightly different result happened.

First, the solution turned REALLY YELLOW, and was full of little bitty flakes that wouldn't dissolve in water. Ning thought "This is it...", but then they turned orange, then red, then brown... Not Good. An extraction with toluene left a large amount of insoluble brown gunk in the bottom. This is not acceptable. So perhaps the future holds some acidic oxidations. But everything ning has read...ugh.

Only thing is, in WATER, in these acidic conditions etc. etc., ning would expect hypochlorous acid, or even chlorine to be generated. Is this the anticipated oxidizing agent? Hmmm...

tengo: One thing ning is not sure about there...did you see that their stock solution was made with perchloric acid...that could bee how those guys are solving their oxidation problems smile

ning
(Hive Bee)
11-24-03 20:12
No 472917
      Relavant bits...

Useful bits from that website:

The oxidation mechanism of APAP is as follows:

At pH values above 6, NAPQI exists in the stable unprotonated form (B).

Under more acidic conditions, NAPQI is immediately protonated (step 2), yielding a less stable but electrochemically active species (C) which rapidly yields (step 3) a hydrated form (D). [...] The pH of the media is 2.

Hydrated NAPQI (D) converts (step 4) to benzoquinone; however, the medium has to be extremely acidic for the rate of the process to be significant enough that reduction of benzoquinone is observed during the cyclic voltammetry experiment. The medium for the cyclic voltammograms detailed in Fig. 3 is 1.8 M H2SO4.
/snip/

This probably suggests what our oxidation conditions should be...

Tengo
(Newbee)
11-25-03 03:16
No 472990
      Some theory first... (also see previous post)

Some theory first... (also see previous post)
Post 472609 (Tengo: "SWIM tried the oxidation in bleach, all a...", Novel Discourse)

And of course the already mentioned patent
http://l2.espacenet.com/espacenet/bnsviewer?CY=gb&LG=en&DB=EPD&PN=EP1068177&ID=WO+++9952860A1+I+

HOAc + NaOCl -> HOCl + NaAc
APAP + HOCl -> NAPQI + HCl + H2O
HCl + NaAc -> HOAc + NaCl
NAPQI + H2O -> BQ + CH3CONH2   (pH<6)

Summarized:
APAP + NaOCl -> BQ + CH3CONH2 + NaCl   (pH<6)

Assuming that HOCl does the oxidation, since it's used to oxidate cyclohexanol in the same way.

SWIM tried this with equimolar amounts of APAP, NaOCl and acetic acid.

15g APAP (unpurified, directly from 30*0,5g tablets)
25ml of 24% acetic acid
150 ml of 5% bleach

Starting at 0°C, slowly adding bleach to the suspension of APAP and acetic acid until the temperature reached 25 °C.

The suspension gets orange immidiately and darkens to orange/brown (brick color) at T+2h.

Another 25ml of 24% acetic acid is added to induce hydrolysis.

At T+5h the reaction has resulted in this:
Brown upper layer and an orange/brown lower layer with white suspended.
These layers are equal in height. If there were an organic layer it should be lower in height since the amount of organic substances are much less than the amount of water.
So it's probably the suspended white that is at the bottom due to gravity.

Adding NaCl (to salt out BQ), nothing visually changes.

Now BQ shouldn't like this polar enviroment and rise to the surface.
Having never seen BQ, SWIM doesn't really know what to look for... MSDS says grey to yellowish-white... Voices at the HIVE say pure BQ is a yellow fluffy powder (and green sparklies when it's contaminated with quinhydrone)

Adding toluene and the suspended white goes to the upper layer.
Probably plenty of unreacted stuff in there (but what, APAP or NAPQI? filler material?).

Adding some HCl and raising the temp (to hydrolize possible unhydrolized NAPQI) and the shit starts polymerizing.

Separating the organic layer and it's reddish-brown...

Conclusion: More or less none (SWIM doesn't now what's in there)

Since HClO is a stronger oxidizing agent than ClO- the equilibrium 2HClO + ClO- <-> ClO3- + 2HCl gets maximally shifted to the right at neutral pH, maybe this affects the reaction.
If it's ClO- and not HOCl that manages to oxidize APAP, then maybe a neutral or acidic reaction isn't the way to go.

ning
(Hive Bee)
11-25-03 21:34
No 473160
      Maybe we should back up a step:

Since we don't know exactly what we're looking for,
ning would suggest this:

First, perform hydrolysis of acetaminophen to p-aminophenol by refluxing with HCl or whatever (posted that stuff).
By this, we know what p-aminophenol looks like.

Then, try the oxidation with p-aminophenol, which we know should work.

If the result is the same damn orange-brown gunk, something funny is happening.

If someone could try oxidizing the p-aminophenol with, say, KMnO4, under strong acidic conditions (H2SO4), then we could have something to compare with.

Ning may have to try that battery-stuff MnO2 oxidation again. Ning seems to remember getting a yellow layer out of that. But the bleach way Must Work!

Anyway, tengo, if you have any sodium sulfite(?) to quench the bleach, you could perhaps try refluxing it with acid for a bit, as I heard the hydrolysis may not always be so fast... if the color changes, it's a good sign.

Ning is working to acquire a refluxing setup, at which point more experimental data will be forthcoming.

By the way, that HOAc oxidation looks sharp. When ning did the oxidation, ze used 70 ml bleach to 1.5 g acetaminophen tablets, so it seems as though your ratio is a little low. Anyway, glad to see the data!

Any other bee want to try this simple experiment? crazy

Tengo
(Newbee)
01-25-04 10:11
No 484502
      See this post for background...

I just found out the colour of NAPQI!
See this post for background...
Post 472990 (Tengo: "Some theory first... (also see previous post)", Novel Discourse)

The red-brown stuff is NAPQI, so the oxidation seems to run fine... It's only that last step, the hydrolysis, that needs tweaking...
From what I can tell, it needs to be done under sufficiently mild conditions to prevent tar formation.
Evidently HCl seems to be to aggressive... But perhaps AcOH would still do it, only with longer reaction time and higher temp.

There is fine line between hydrolysis and polymerization ;)

/T

ning
(acetaminophanatic)
04-16-04 21:04
No 501121
User Picture       Good to see we're still active

Ning hasn't forgotten this most-beloved thread. Hopefully some further experimentation will bee forthcoming.

Tengo, I'm actually rather interested in the hydrogen peroxide oxidation patent. It was you who posted that, right? I think that part of the tarring's cause may be halogenation, which of course H2O2 won't have a problem with. I'm thinking FeCl2, CuSO4, or some of my MnO2 will work nicely as catalyst, and IIRC, the patent diluted the H2O2 down to about 5% or so. Which suggests that 3% storebought will probably work too. I have a feeling this may be much cleaner reaction. They got nearly quantitative yields of quinonimine, also.

I want see what happens if the sludge is refluxed for an hour in dilute HCl. It wouldn't bee too surprising if something came out of it. I always got the feeling that the stuff wasn't hydrolyzing for some reason.

Bleach is powerful, but so annoying to deal with. Such complex chemistry it has!

Catching a buzz @ the Hive

	https://the-hive.archive.erowid.org	the-hive@erowid.org



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