Sciencemadness Discussion Board - Synthesis of isatin from indigo via ozone, HNO3 and others

Synthesis of isatin from indigo via ozone, HNO3 and others

miamicanes - 2-10-2004 at 19:35

A little while ago, I managed to find another (seemingly) straightforward way to synthesize isatin from indigo that I admittedly like a lot better than the nitric acid method (mainly because it doesn't create picric acid as a waste product).

It looks like the reaction is:

C16H10N2O2 + O3 --> 2 C8H5NO2 + O (which I assume finds another oxygen fairly quickly to join and produce O2).

So... how might I go about actually getting this to work using a small ebay-ish ozone generator (like this one -- http://cgi.ebay.com/ws/eBayISAPI.dll?ViewItem&category=2...)?

idea #1) dump 25g indigo into 1L filter flask and fill 1/3 with deionized water. Connect plastic tube and aquarium airstone to ozone generator (passing through hole in the flask's rubber stopper) and insert airstone so it's bubbling ozone from the bottom of the beaker. Agitate and swirl until the indigo seems to have completely oxidized into isatin.

idea #2) cover bottom of filter flask with thin layer of indigo. Run airstone's tube through hole in rubber stopper, with enough length to reach the bottom of the flask. Insert the stopper into the flask and seal tightly. Connect another air tube to the filter flask's air hole and connect the other end to the sink-mounted aspirator. Turn on the water and ozone generator. Hope that the ozone concentration gets high enough to actually work.

Things I can think of that might go wrong:

* The reaction might be strongly exothermic and melt the airstone and/or air tube, and quite possibly blow the stopper out of the flask and boil over.

* The cheap ozone generator might be the equivalent of trying to turn the ocean yellow by peeing into the atlantic off a pier.

* It might be necessary to dissolve the indigo into a solution using some strong acid that would either dissolve the airstone and/or pipe, or react violently with the ozone.

What do you think? Should I go ahead and order the sub-$50 ozone generator/air pump and hope for the best? Or will I really need to get one that's a lot more powerful and expensive for it to work? Is it likely to be straightforward and easy to do, or (as was the case with the nitric acid method) is there some major catch lurking in the shadows ready to cause major headaches with THIS method too?

[Edited on 14-10-2004 by chemoleo]

neutrino - 2-10-2004 at 20:05

There are chemical ways of making ozone that should be much cheaper than getting a generator and yeild much purer ozone. There was a thread about this here, just search for it.

miamicanes - 2-10-2004 at 20:23

I saw the threads... the impression I got was that the various chemical methods proposed involved chemicals that were hard to get and/or dangerous to work with & electronic (but not corona discharge) generators were the best compromise (not terribly efficient, but fairly cheap, convenient, and generally adequate for the task)...

miamicanes - 2-10-2004 at 21:17

Whoops. It looks like I didn't get the reaction quite right. Apparently, the reaction's products are isatin and isatoic anhydride:

C16H10N2O2 + O3 --> C8H5NO2 + C8H5NO3

It looks like the reaction will still work reasonably well, yielding 1/2 mole of Isatin per mole of indigotin (plus 1/2 mole of isatoic anhydride). As luck would have it, isatin is practically insoluble in water, and I'm assuming that by definition isatoic anhydride would immediately react with the water to produce isatoic acid, which appears to be fairly tame and dump-down-the-sink-able (compared to picric acid). So hopefully, the outcome would be isatin solids suspended in isatoic acid, ready to be filtered out.

From what I can tell, the Enaly 300U ozone generator looks like it might be good enough to do the trick. It's rated for 200-300mg/O3/hour and comes with clear tubing and airstone. Plus, it even has an intake that can be fed pure O2 if nitrogen from the air becomes a problem.

Of course, there are still a few major questions to resolve... like how exothermic the reaction of the indigotin and ozone (or the isatoic anhydride and water produced by the main reaction) will be. I suspect it'll be pretty tame, though... the book I saw referred to ozonating indigotin in the context of sanitizing aquarium environments (I love Amazon.com's search inside... ) :cool:

[Edited on 3-10-2004 by miamicanes]

Attempt #1 at isatin synthesis -- failed.

miamicanes - 7-10-2004 at 21:02

Well, I made my first attempt at synthesizing isatin from indigo using ozone tonight and failed miserably.

Procedure:

combined 5g synthetic indigo w/approx. 250mL distilled water in 1L flask and mixed into solution/suspension.

threaded plastic tube through 2-hole flask stopper and connected one end to ozone generator and other end to airstone.

lowered airstone into indigo+water and turned on ozone generator. watched it foam for 3 hours. When I finally ran out of patience, there was what appeared to be a shiny yellow film atop a layer of purple foamy scum, but the bulk of the solution appeared to be unchanged, and after allowing the liquid to settle down for 10 minutes after turning off the ozone generator and removing the airstone, most of the discernible top layer of scum was gone.

With minimal optimism, I filtered the solution through #2 whatman paper, and ended up with nothing more than a filter paper caked with indigo. No trace of isatin. For the hell of it, I measured the pH -- 4.48.

So... does anyone have any idea as to what might have gone wrong? Was the indigo solution too strong? Too dilute? Do I need to heat the mixture? Would using 40vol. hydrogen peroxide (12% w/v) instead of distilled water help (by providing more spare oxygen atoms), hinder (by aggressively cannibalizing the ozone to create molecular oxygen, leaving nothing to oxidize the indigo), or make no real difference?

I just did some calculations now, and suspect my biggest problem might have been not waiting long enough. As far as I can tell:

1mol indigotin (C16H10N2O2) = 262.28g

5g indigotin = .019mol

1mol O3 = 48g

.019mol O3 = .91g

assuming 100% efficiency @ 200mg/hour, and one ozone molecule oxidizing one indigotin molecule, it looks like it will require at least 5 hours (probably more like 10-24) to oxidize .019 mol indigotin using .019mol O3 to produce .019mol isatin precipitate and .019mol isatoic acid (presumably aqueous and hopefully passable through a filter).

Is this a reaction that's safe to leave unattended for extended periods of time? Like, say, running in the shed in the back yard overnight and maybe all day while I'm at work (theory: if it DOES blow up or something, at least it won't destroy the house too... though it would definitely still suck if it happened...).

As far as I can tell it doesn't produce anything explosive... but I can't help wondering what mischief the handfull of nitrogen molecules that get turned into NO2(?) by the ozone generator's corona and get injected into the solution along with the ozone might become...

Also, am I correct in assuming that I'll know when the indigo has been fully oxidized because it'll no longer be blue (I know Isatin is yellow precipitate, but I'm not sure what color hydrated isatoic acid is.)

Also... is diluted isatoic acid safe to dump down the sink? In the back yard?

miamicanes - 8-10-2004 at 05:05

update:

It looks like ozone was a necessary, but not sufficient, component of the reaction. Apparently, ultraviolet light is also necessary.

So... it looks like tonight I'll get to go on a desperate scavenger hunt for a meaningful (yet not terribly expensive) source of ultraviolet light.

I'm thinking that an aquarium-type setup might work best:

flask w/2-hole stopper filled with indigo + deionized water mixture -> outbound tube -> impeller-type aquarium or pond pump -> venturi tee fed with output from ozone generator -> UV aquarium or pond sterilizer -> inbound tube -> flask

The idea being that the pump will slowly move water through the venturi tube (where ozonated air will get injected into it), then immediately pass into the sterilizer chamber to get exposed to ultraviolet light before the isatin, isatoic acid, and unreacted indigo will return to the flask.

Things I'm open to suggestions on:

* IS C8H5NO3 "isatoic acid?"

* how watery should the mixture be?

* should the pump be slow (to maximize the amount of time the ozone-injected indigo mixture spends in the sterilizer tube after injection), or a bit faster (if the UV will quickly break down the ozone before it passes far anyway)

* what is aqueous Isatoic acid (C8H5NO3) like? Will it pass through the filter paper (leaving behind the precipitated isatin)? I'm assuming that, by definition of "hydration", hydrated C8H5NO3 will fully dissolve into water and not get caught in the filter paper.

* what grade of filter paper should I use (I have #2 whatman handy, but can get others today)?

* what does hydrated isatoic acid look like? I haven't been able to find a decent description anywhere online (everything refers to it in its anhydrous form). What's its pH? General appearance (I'm assuming it's not blue, and probably falls somewhere between yellow and clear).

* is isatoic acid flammable, explosive, or toxic? What reagent acid is it comparable to with respect to reactivity (ie, citric acid? acetic acid? hydrochloric acid? sulfuric acid? nitric acid? god forbid, picric acid?)

I could definitely use a few links to online articles google missed regarding hydrated isatoic acid, as well as anything that discusses in depth the reaction between nitric acid and indigotin (I still might get desperate and try that route tomorrow... but not until I feel confident that I've got a really good understanding about the whole reaction from start to finish. There's no way in hell I'm going to just blindly start adding nitric acid to indigo and hope it doesn't explode...).

chemoleo - 8-10-2004 at 09:45

I had a look around, and found this:
http://employees.csbsju.edu/hjakubowski/classes/ch331/oxphos...

are you using indigo carmine? (which presumably is the sulphonic acid form)? Presumably the acid form is easier to isolate, as it will produce precipitable salts.

Anyway, more importantly, have a look at this:
http://www.orgsyn.org/orgsyn/prep.asp?prep=cv1p0327
It describes isatin as large brown-red crystals which melt at 196–197°, when recrystallised in glacial acetic acid. Also, there is a large reference section on the preparation of isatin from indigo via oxidation. This may be most helpful to you.

Regarding your experimental difficulties, what means do you have to identify the isatin? Anymore than 'a yellow liquid'? Did you weigh the indigo before and after the reaction? Any change?
Also, it seems a basic solution brings the isatin into solution, while acidifying it leads to its precipitation. Maybe thats the way forward to identify it.

What do you want the isatin for?

PS the preparation of isatin from aniline and hydroxylamine actually seems quite simple, once you have anilin.

[Edited on 8-10-2004 by chemoleo]

neutrino - 8-10-2004 at 19:03

If you want UV, just leave the thing running in the sun.

miamicanes - 8-10-2004 at 22:45

Well, round #2 is underway, with slightly refined hardware.

Procedure so far:

approx. 3/4 gallon sodium-free distilled water (I couldn't find actual deionized+distilled, so I had to settle for the best compromise available) added to new, clean plastic bucket.

aquarium powerhead submerged in water in bucket.

enlay OZX-300U ozone generator (rated for 200-300mg/hour) attached to powerhead's venturi air intake to inject ozone into water.

powerhead's output connected to Turbo-Twist 6X UV sterilizer (18w cf UV, with spiral internal water path to increase exposure time).

sterilizer's output dumped back into bucket to marinate further and repeat the trip.

turned on powerhead. Verified no leaks.

turned on ozonator. Observed bubbles.

turned on sterilizer and allowed to run for 15 minutes. No explosions, no unusual heat.

Added 10mg indigotin (C16H10N2O2, CAS 482-89-3, MW 262.27)

Observed closely for 1 hour to make sure it didn't look like it was going to suddenly become wildly exothermic. Nowhere close.

Observed casually for another hour. Still looks quite under control. Shiny, metallic-looking scum over most of the liquid's surface in the bucket. It might be contamination, but I saw a few distinctly yellow shiny flakes. Dare I say, "Isatin?"

It looks like it's going to take AT LEAST 8-12 hours to get anywhere close to oxidizing all the indigo into isatin and waste. The exact outcome is still anybody's guess... I found about 9 sources online (5 or 6 via amazon.com's "look inside"

that referred to oxidizing indigotin with ozone, with three different opinions as to the outcome:

1) C16H10N2O2 + 2 O3 + water --(uv)--> 2 C8H5NO2 + H2O2 [this is obviously the one I like, since it transforms all the indigotin into isatin with no hazardous wastes.

2) C16H10N2O2 + O3 --> C8H5NO2 + C8H5NO3 [1 Isatin, 1 isatoic anhydride that would probably end up hydrated since the reaction is taking place in water)

3) indigotin + O3 --> isatin + anthranilic acid + O2. God knows where this one came from... I only saw it listed in one source, but remember scratching my head wondering what the hell the author was thinking. As far as I can tell, anthranilic acid isn't another name for hydrated isatoic acid.

Anyone care to speculate as to which one might be most likely?

Anyway, getting back to why I think it's going to be a
L O N G ...
reaction, I pulled out the calculator for the first equation:

1 mole indigotin = 262.27g
I used 10g = .038mol
1mol O3 ~= 48g
.038mol O3 = 1.83g
but according to equation 1, I need two O3 molecules for each indigotin, so that means I'll need 2x.038mol = 1.83g x 2 = 3.66g O3.

At the most optimistic rate (300mg/hour, 100% utilization), that translates into 12 hours. At 200mg/hour, that translates into 18 hours. I have no idea what the actual ozone utilization efficiency might be, but I'm going to assume that 100% is wildly optimistic and figure that it'll take at least 50% longer to complete the reaction. Of course, if one of the single-ozone-reagent equations applies, that would cut the time roughly in half.

does this rationale seem correct?

The jury's still out, but one or two of the sources mentioned needing to heat the reacted mixture prior to filtering to make the new isatin molecules crystallize. Anyone have any suggestions regarding time & temperature?

----------------

responding to questions...

no, it's not indigo carmine. it's indigotin (aka "indigo blue" and synthetic indigo. This is the active molecule that actually matters).

I knew about the sulphonic acid form, but skipped over it for now until I first verify that the experiment works with normal, plain isatin. I suspect the sulphonic acid form won't work. Now, if I knew how to turn THAT into pure isatin... ;-)

the purpose? a few weeks ago I tripped across a formula for a novel hair dye that was discovered about 20 years ago, but never marketed (I'm guessing because by its very nature it has to have a volatile alcohol base, which probably freaked out their liability lawyers. Not to mention it probably violates California and New York clean air regulations for VOC.). Its big appeal is that it apparently has minimal affinity for skin, but develops rapidly in contact with hair (something in hair acts as a catalyst).

One interesting bit of trivia... apparently, someone discovered the isatin-in-hair reaction more than a century ago and found the color to be both permanent and offensive. I think this was before the discovery of aniline dyes, so it never occurred to him to try adding one (like p-aminophenol) to the equation (apparently, p-aminophenol nudges the color towards medium-dark brown w/yellow undertones. yay! no red!)

What's really sad is that if Isatin were readily available for purchase by individuals in its pure form, the formula itself is pretty trivial... 1.5g isatin + 1g p-aminophenol dissolved in 30mL ethanol, then 70mL water + some small amount of gum arabic or similar agent added for viscosity.

[Edited on 9-10-2004 by miamicanes]

miamicanes - 8-10-2004 at 23:02

pH update...

at t=3 hours, I had a *hell* of a time trying to get anything resembling a stable pH reading using the digital pH meter.

The frothy scum seemed to have a pH of approximately 6, +/- .5

The stream of fluid coming out of the return tube (having just made the trip through the uv sterilizer after its ozone injection) had a pH of approximately 5, +/- .25

miamicanes - 9-10-2004 at 08:31

t=12h update

My initial impression was disappointment. The solution doesn't appear to have lightened or otherwise changed color since last night.

HOWEVER... the pH has definitely dropped. The liquid coming from the return tube is down to a fairly stable 3.7 (3.5 to 3.8), and the liquid in the bucket itself has pH~= 4 (3.65-4.8).

There's also a crusty dark purple scum along the surface at the bucket's walls. I'm torn between trying to scrape it off & try to heat and filter it (on the chance it's isatin + isatoic acid), and rinsing it down into the pail with the rest using a wash bottle (on the likelihood that it's just splashed indigotin that had water evaporate since it's quite dark purple).

I suspect that the reaction will probably speed up rapidly once the color begins to lighten. Right now, the dark violet indigotin is probably absorbing and blocking the UV from passing more than a millimeter or two, so it can only break up ozone molecules that are close to the lamp. OTOH, as the solution clarifies (I hope), the UV will be able to make it farther -- affecting ozone molecules farther away and increasing the effect on the reaction.

I'm tempted to try slowing down the powerhead. Last night I cranked it to max in case the reaction inside the UV sterilizer got too active and threw off too much heat. Seeing how that hasn't happened, it might help to give the fluid more time inside to interact with the UV (from the smell, I can tell that lots of ozone is emerging from the sterilizer intact).

chemoleo - 9-10-2004 at 09:34

Isn't UV absorbed by aromatics of any nature regardless? A normal phenhydroxy group absorbs nearly up to 300 nm... so isatoic acid is bound to absorb itself too. So a reaction is bound to occur, as you say, only for 1-2 mm into the mixture.
In addition, did you check whether your glass is UV transmissible? Maybe you'd need a quartz container anyway to make this work

miamicanes - 9-10-2004 at 09:37

The UV is provided by a Turbo-Twist 6X aquarium/pond sterilizer. It's basically a UV compact fluorescent (18w) inside a watertight glass cylinder (which presumably doesn't block the UV), inside a larger black plastic cylinder through which the liquid being exposed to the UV passes.

Marvin - 9-10-2004 at 10:10

According to what little Ive been able to find isatoic acid is not a required byproduct.

Indigo oxidised with dilute nitric acid in the cold is supposed to go to isatin and nothing else. If the acid is hot it also produces some nitrosalicylic acid or picric acid but kept dilute and cold these are not supposed to form.

The isatin formed is supposed to be yellow and insoluable but it should be easy to tell from nitration products if the acid you use is too concentrated.

I would be inclined to skip the ozone method.

miamicanes - 9-10-2004 at 10:20

How sure are you that dilute, cold nitric acid will react with indigo blue to form isatin with little/no picric acid? I was under the impression that the two pretty much went hand-in-hand as byproducts of oxidation via nitric acid. If you're right and I'm wrong I'll definitely be happy and you'll have made my day :cool:

It's weird.... supposedly, the reaction between nitric acid and indigo was one of the first to be studied and documented two centuries ago, but if you look for details on the internet, you'd barely know it even existed except as a historical footnote. I guess it's not an experiment really suitable for inclusion in a glossy, lavishly illustrated college chem class lab manual with step-by-step instructions that put most cookbooks to shame

Also, what would you define as "dilute" (I have a liter of 70% (16M?) technical-grade nitric acid available to dilute. I'm just paranoid as hell about going anywhere near TNP for a few reasons, including:

* TNP residue is the most dangerous part of all. I suspect there's going to be lots of dried residue on the filter paper, buechner funnel, stir rods, and just about everything that comes in contact with the solution at some point in time.

* Ultimately, this is something that's going to wind up in hair... I have no idea how much damage a tiny crystal of TNP can do, but I suspect its reaction during a potential future encounter with hydrogen peroxide probably wouldn't be pleasant.

* Just about every reference I've seen to TNP mentions TNT in the next sentence -- the one chemical that's probably earned a Darwin Award for more home chemists than any other...

Mitigating the fear (slightly) is the fact that TNT's main danger comes from the fact that the reaction can easily accelerate out of control (boom), not from the actual power of intentionally-detonated TNT itself (which I suspect is where the two are really comparable). Also, I can't help wondering how garment makers managed to oxidize indigo with nitric acid to make picric acid for use as a yellow dye for nearly half a century before anyone even realized it IS explosive...

I'll admit that I can't help but suspect that the reaction most businesses, schools, and government agencies seem to have upon discovering an old jar of picric acid might be just a wee bit excessive, fueled more by the perception that going WAY overboard and treating it like plutonium-laced plastic explosive is the normal, rational way to handle it...

[Edited on 9-10-2004 by miamicanes]

neutrino - 9-10-2004 at 12:43

TNT isn't really that dangerous. I have never heard of a runaway reaction causing an explosion for one simple reason: it can't. TNT is a secondary explosive, which means that it is very hard to detonate, requiring powerful blasting cap. Even if you pound on it with a hammer, you’re unlikely to get a detonation. If you light it, it will only burn. In short, there’s no way the TNT will ever explode, especially with the tiny batches you’re working with.

miamicanes - 9-10-2004 at 16:01

Oops. I meant nitroglycerine (which can definitely accelerate out of control if you're not incredibly careful and lucky).

I'm also starting to have second thoughts as to just how dangerous random, scattered picric acid residue might be. I'm starting to suspect that a single crystal the size of a grain of salt might produce an effect comparable to the quasi-firecrackers that consist of some a rock coated with some chemical wrapped in a piece of tissue paper that detonate when you throw them on the ground. Unlike, say, a jar of picric acid with crystals around the lid, there's no reservoir of picric acid a few inches away ready to get detonated as well.

Still, I think having intimate bodily contact with detonating picric acid -- even a crystal the size of a grain of salt -- wouldn't be pleasant, even if it weren't necessarily fatal or even serious. Probably comparable to having a glob of molten solder fall from a soldering iron onto your leg (been there, done it circa 7th grade. Still have the scar.)

vulture - 10-10-2004 at 05:57

DON'T POST A NEW THREAD FOR EVERY ATTEMPT!!! :mad:

-----------------------------------------------------

Attempt #2 at isatin synthesis -- not yet.

Well, it's been 18 hours, and the solution is just as dark as it was yesterday. No visible isatin precipitate, either.

Sigh. It looked so elegantly simple on paper... bring ozone into contact with the indigo and watch the isatin precipitate out as the ozone gives up an oxygen atom and neatly cleaves the indigotin molecule in half...

I'm open to suggestions as to what to try tomorrow. Here are some of my random thoughts:

* I should get a new bucket -- saving today's solution in the old one -- and tomorrow try adding today's solution to water a little bit at a time. The general theory being that the reduced concentration will expand the reach of the UV and let it work harder on the smaller amount.

* I need to find a way to expose the ozonated solution to direct sunlight. There's plenty of ozone (quite a bit is NOT getting destroyed by the pass through the UV sterilizer), but the solution just isn't getting enough of a dose from the 18w sterilizer.

Of course, I'm having a few darker thoughts... like the possibility that nothing short of an industrial-strength ozonator and several hundred watts of UV (comparable to direct sunlight) will really do the job.

Sigh.

[Edited on 10-10-2004 by miamicanes]
--------------------------------------------------------

vulture - 10-10-2004 at 05:58

Again, from yet another new thread about this! :mad:

---------------------------------------------------
Attempt #3 at isatin synthesis... working!!!

I couldn't wait until the sun came up tomorrow to try exposing the ozonated indigotin+water mixture to sunlight, so I tried something a bit different -- massively diluting the mixture to see whether decreasing the concentration would let the UV rays reach farther and influence more ozone molecules.

So far, it seems to be (slowly) working. I'm seeing tiny yellow flecks appear in the mixture. It's not much yet, but it's a start.

A little more good news. Yesterday, the tube connecting the ozone generator to the powerhead got stained blue about 8 inches in from the end when indigo-containing water got blown up into it by the powerhead when I briefly turned off the ozone generator. As of 5 minutes ago, it's now YELLOW! yay! finally, tangible evidence that the ozone is actually doing something :-)

1,000,000 indigo molecules down, 20,474,800,000,000,000,000,000 to go

Bringing one of my other posts into the current discussion, I went out to home depot and bought two coils of plastic tubing. One is translucent frosty white polyethylene; the other is clear vinyl. I'm thinking about mounting a big spiral using one of them on a piece of plywood to put in direct sunlight to take advantage of the massively more intense UV coming from the sun during the day.

Which one is likely to offer the least resistance to UV-B radiation? On one hand, somebody mentioned that polyethylene food wrap has a single bond and should offer little resistance. As I said, one of the tubes is polyethylene... but I guess the fact that it's frosty white is leading me to believe that it won't have quite the same effect as hair-thin clear saran wrap. The other is clear, but I think vinyl has a double bond, which someone else said will block UV.

I'd rather return all the stuff to Home Depot if neither tube is likely to help matters (I blew another thirty bucks there tonight), but on the other hand I'll definitely implement one (or both!) if anyone thinks one or both will let a useful amount of solar UV through.

Hmmm. If nothing else, the vinyl one will probably absorb lots of heat and raise the fluid's temperature a few degrees. Maybe sending the ozonated mixture into the UV chamber 10-25 degrees hotter might help, too...

miamicanes - 11-10-2004 at 08:09

Last night, I was happy. After running the apparatus all day with diluted indigo, it finally turned yellow.

One problem, though... the Isatin appears to be gone. More online research suggests the reason why, as well as the reason for the divergence of opinion as to the products of the indigo + ozone + uv reaction:

ozone + uv oxidizes indigo into isatin, but continued exposure of isatin to ozone + uv apparently transforms it into anthranilic acid (ortho-aminobenzoic acid). In other words, I went too far.

sigh.

So... can anyone suggest a way to reduce anthranilic acid back down to isatin?

[Edited on 11-10-2004 by miamicanes]

miamicanes - 11-10-2004 at 18:39

For what it's worth, here are some details about the first batch.

Initially, the mixture was green-yellow with visible specks of unoxidized indigotin remaining. I heated 1L to some point with visible heat-induced currents just short of boiling (no thermometer. oops.) and let it cool, then filtered it through #2 whatman paper. While the first batch was drying, I repeated the procedure with the second half of the first batch (a little under 1L).

No red or yellow precipitate was observed on the filter paper. A bit of indigo residue, but that's about all. The filtered liquid was now yellow-green.

18 hours later (after work today), I decided to make one last try at finding isatin in the liquid. This time, I only filled the pyrex measuring cup 1/3 (to give plenty of room for foam, etc) and heated it to a rolling boil. I let it boil for 10 minutes, then let it cool for 2 hours.

No precipitate. Just clear yellow-green liquid.

I decided to compare the pH of the three groups:

the first batch to be heated (but not boiled) and filtered: 5.44

what was left of the second batch to be heated (but not boiled): 5.15.

The portion of the second batch that was heated to a rolling boil today: 5.26.

The pH readings were fairly stable, +/- .02.

The difference between the first batch to be heated and the second batch to be heated can be partially explained by the fact that the fluid comprising the second batch had an additional 3 hours of ozonation and UV exposure (more intense than usual, because half of the original quantity was gone from the system, so each bit was getting sent through the loop twice as often).

I'm not really sure why the unboiled liquid is more acidic than the boiled liquid, unless I was REALLY boiling away more of the presumably acidic mystery liquid than the water diluting it.

Any ideas as to what the yellow liquid might be? It's obviously acidic, but not terribly reactive. I've had lots of casual bodily contact with it... no burns, tingling, rash, or even an itch. It's not odorless, but I can't really think of anything to compare it to. Given a choice between smelling it and not smelling it I'd rather not smell it, but the smell isn't bad enough to motivate me to really try avoiding or reducing it if I randomly encountered it somewhere.

I can think of two obvious possibilities:

* hydrated isatoic anhydride (isatoic acid?)

* anthranilic acid

I doubt there's any significant amount of Isatin dissolved in the liquid. For one thing, Isatin is practically insoluble in cold water, and minimally soluble in hot water. From what I've read, if there were any Isatin in there, it should have fallen out as crystals when the aggressively boiled liquid cooled.

If it's hydrated isatoic anhydride or anthranilic acid, is there any straightforward way to react it back into isatin?

I want to think it might be possible to reduce isatoic acid into isatin precipitate by bubbling hydrogen gas diluted with helium (to keep the reaction from getting too violent) into the liquid in the hope that the extra oxygen that makes the difference between isatin and isatoic anhydride might prefer to be the backbone of a water molecule instead of a mere cling-on to a big organic molecule... but that assumes I could actually talk someone at Airgas or some other company into actually selling a cylinder of hydrogen diluted with helium. Seriously doubtful.

As a practical matter, I'd probably wind up having to drop a penny into a flask, pour the liquid into a tall, narrow container with a tube leading to an airstone at the bottom, and run the other end of the tube through a rubber stopper capable of fitting tightly over the penny-containing flask, add acid, plug the opening, and run for cover...

If there's some straightforward way to turn the mystery liquid into isatin precipitate, this method will be perfect because it'll mean I can let "most" of the indigo oxidize, then simply filter out all the remaining indigo before doing the final reaction against the "clean" liquid...

On the other hand, I just might get desperate enough to try using nitric acid tomorrow night. One question, though.. what, exactly, constitutes "dilute" nitric acid (relative to 16M/70% non-fuming)?

[Edited on 12-10-2004 by miamicanes]

Marvin - 12-10-2004 at 03:20

"If it's hydrated isatoic anhydride or anthranilic acid, is there any straightforward way to react it back into isatin? "

If its gone this far its destroyed, youve broken a carbon chain and they dont fix easily. The only way I see to go backwards from anthranilic acid for example would involve cyanide.

Hydrogen tends to be used as a rather specific reducing agent and most people very sensibly avoid it. Helium is much much more expensive than hydrogen and if dilution was needed it would be done with 2 tanks, say hydrogen and argon with a mixer tap. Mostly hydrogen reductions do not go easily and need high pressure and/or high temperature. They do produce a lot of heat when they do go though, you're right. I cant think of any hydrogen reduction that links 2 unlinked carbon atoms.

When it comes to making isatin I have no idea at all what 'dilute' would indicate. I would suggest you try a few test tube scale reactions, few mg of indigo, and start with say 10 or 20% and see how concentrated to make it go yellow in a fairly short space of time without heating. If you make any quantities of picric acid by accident on this scale there really is no hazard unless you drink it. Just pour the solutions down the sink. If you can do an accurate melting point this would confirm you have what you think you have, maybe after a single purification stage.

miamicanes - 12-10-2004 at 05:59

Well, last night I found out that there is a way to turn anthranilic acid into isatoic anhydride, but it's utterly out of the question -- reacting it with phosgene. Argh.

I assume that you mean that even if the spurious oxygen in isatoic anhydride were to join a nearby H2 molecule drifting by, the two carbons previously bonded to the oxygen wouldn't just bond with each other and close the ring automatically.

I'm still going to experiment with the mystery fluid... there's a tiny chance that if it IS (mostly) isatoic acid instead of anthranilic acid, it might still do Isatin's job. I doubt it, but at this point I've gone through so much work to make it, I might as well play with it a little more to see what happens when it's brought together with 1% w/v p-aminophenol.

One other possibility that I haven't had time to explore yet is whether it might be straightforward (if it's anthranilic acid) to reduce it to aniline by stealing away the COOH, then try using the aniline to build a new isatin molecule. I vaguely remember reading about a synthesis reaction involving aniline at some point over the past few days, but wrote it off because I didn't have aniline available anyway.

God, I really wish I could just buy the stuff. So far I've spent close to $400 trying to synthesize something that's not even restricted or toxic and costs about 35 cents/gram to buy if you're a commercial research lab. :mad:

[Edited on 12-10-2004 by miamicanes]

miamicanes - 12-10-2004 at 20:54

Just to conclude this thread in case anybody wants to try ozonating indigo to get Isatin -- it doesn't work.

Ozone + UV-B does neatly cleave indigo molecules into two isatin molecules. Unfortunately, it doesn't stop there. Continued exposure to Ozone + UV-B causes the isatin to decompose into anthranilic acid. Herein lies the catch... by the time the last of the indigo gets cut in half and transformed into isatin, most of the isatin will have been destroyed.

Thus, ozone + UV is feasible as a method for decomposing indigo into isatin and anthranilic acid as long as your goal is to be rid of the indigo, but it's NOT feasible as a method for synthesizing isatin from indigo if you need to actually preserve the isatin once it's created.

On top of that, the amount you can process at any given moment in time is ridiculously small... in a system consisting of a pump, tank, ozone generator capable of 200-300mg/hour, and 18w UV sterilizer whose total operating capacity is one gallon of water, you can MAYBE process a whole whopping gram of indigo at a time before the indigo itself begins to block too much UV... and you're looking at 24-48 hours of running time just to get that far.

On the other hand, if your ultimate goal is extremely dilute anthranilic acid, this system works beautifully because it's totally safe. But for Isatin, forget about it.

Well, there is one possibility I didn't bother to explore due to cost feasibility... imagine a system built into a large igloo cooler with high-power fluorescent UV tubes (say, 2 to 4 40w+ tubes w/10% min efficiency @ UV-b), a BIG ozone generator capable of generating 1000mg/hour, and a pump with ultrasonic mister that sprays a fine mist of indigo solution into the ozone-rich air inside the cooler directly beneath the UV tubes. In such a system, it might be possible to fry enough of the indigo quickly enough to avoid destroying too much isatin. But this little experiment will realistically cost you AT LEAST $500 to try... and quite possibly won't work either. So think carefully before pulling out your visa card and hitting eBay...

Isatin synthesis via Nitric acid and Indigo

miamicanes - 13-10-2004 at 17:01

OK, I bit the bullet tonight and decided to try oxidizing the indigo using nitric acid despite my misgivings about the safety of doing so.

The good news: I didn't end up with a black tarry mess, nor did anything blow up.

The bad news: I'm not entirely sure what I ended up with.

Ingredients:

4g synthetic indigo blue ("indigotin"

, mixed with small amount of distilled+deionized water to make thick paste.

approximately 8 mL 70%(16M) technical grade nitric acid, added a couple of drops at a time over the span of 3 hours.

It took about 5 mL of nitric acid to see any visible reaction.

At first, yellow precipitate formed and rose to the surface. It looked like this was going to be pretty easy to do after all...

...Then, it turned into an oily orange-yellow liquid that I ended up skimming off the top using a pipette and filtered through #2 whatman paper.

Its massively diluted (approx. 20 parts water to one part oily liquid) pH is approximately 3.0. Despite the oily appearance, it appears to have dissolved thoroughly into the water. It doesn't smell particularly acidic, but there seems to be WAY too much of it to be Isatin (plus, I vaguely remember reading somewhere that Isatin is minimally soluble in water).

I'm hoping it's not picric acid. I suspect it is.

The gunk in the filter paper looks like unoxidized indigo. No apparent yellow crystals or precipitate.

Any suggestions what to do next? Or ideas as to what the hell the oily yellow-orange liquid I now have a (highly-diluted) liter of is?

[Edited on 14-10-2004 by miamicanes]

neutrino - 13-10-2004 at 19:16

Picric acid is not a liquid at room temperature, although there's a chance you might have a solution of it. I think that the odd results are due to not using enough acid. If the pH = 3, either you had some incredible stroke of luck and get exactly stoichiometric amounts, or (much more likely) there was a lack of acid. With some inorganic reactions at least, you need at least one reactant in slight excess before the products become visible at all.

chemoleo - 13-10-2004 at 19:38

I read somewhere that the principal product of nitration of indigo is picric acid. I don't know under which conditions that is supposed to hold, but that was one of the reasons why I purchased indigo a long time ago.
However, looking at your conditions, you may have gotten a di or mono nitrophenol.
I don't think you can argue on the basis of solubility, as phenol nitration on its own doesnt result in the immediate precipitation of picric acid. This in fact only happens after dilution with ice-cold water.

Anway, this thread is merged with the existing isatin threads (this is now the THIRD ONE). Miamicanes, there is no NEED to create a new thread for every other experimental method you try. Unless there are masses of posts on each method (therefore justifying a thread in each case).

[Edited on 14-10-2004 by chemoleo]

miamicanes - 13-10-2004 at 20:24

Well, in this case, I thought it justified a new thread because it's an entirely different reaction (vs ozone... same ultimate goal, different set of problems and complications).

So... COLD water increases the likelihood/quantity of picric acid? Sigh. I thought it was the other way around (keeping the reaction slow, cold, and dilute to minimize the amount of picric acid produced).

Does anybody actually have a college textbook (probably pre-1965, when colleges wouldn't have been scared shitless of liability and would have actually let students do it) that describes in some reasonable detail how to properly oxidize indigo using nitric acid?

Confession: this was actually my third attempt with nitric acid. The first ended with the destruction of $25 or so worth of glassware because I got impatient, went overboard with the non-dilute nitric acid, and wound up with a mini-volcano-in-a-flask spewing black tar above what was obvious picric acid. The second time around, I was too cautious, over-diluted the nitric acid, and ended up with what felt like a ticking time bomb (90% dilute nitric acid, 10% indigo sludge, pH of .95, with the flask sitting in a bowl of ice water. I chickened out and dumped the solution after mulling what might happen once the solution hit room temperature with that much acid waiting to spring into action...). This time I tried to go for the happy medium... minimal water, 70% acid straight from the bottle, but only adding it one drop at a time. With occasional squirts of cold water into the solution if the reaction seemed to be speeding up too much, and getting ready to form volcano #2 & ruin another flask.

[Edited on 14-10-2004 by miamicanes]

chemoleo - 13-10-2004 at 20:34

No, what I was saying is that the reaction conditions (highly acidic, hot) don't favour the potential precipitation of picric acid, and mono/di-nitro derivatives. It only becomes apparent when it is diluted with ice cold water, afaik.
Therefore you cannot judge whether you got picric acid (or not) just by looking at whether it is soluble in your reaction mixture or not. That's all.
What is '90% dilute nitric acid'? Is it in fact 10% (10 g HNO3 and 90 g H2O)?
Anyway.. I am sure there are some patents/preps around as to how to prepare picric acid from indigo. I guess these are the conditions you'd exactly try to avoid!!!!!!

PS if everyone started posting a new thread for each method for the same final product (i.e. sodium), we'd have at least 5 times the number of threads we have now. Honestly, do you think that'd make sense?

PPS Interesting anyway that you got a runaway. I can't remember this happening when I tried it. But at least it didn't explode. I think someone even did a study once to deliberatly cause runaways, and see whether one'd achieve detonation. They never did. So don't worry too much. Runaway, yes (lots of NO2, heat etc), but detonation, NO (at least these guys couldn't trigger it, neither did anyone seem to in the existing forums). So it looks like you are physically safe, as long as you are upwind.

[Edited on 14-10-2004 by chemoleo]

miamicanes - 13-10-2004 at 21:00

Quote:

'90% dilute nitric acid'?

about 10mL of indigo + water, 90mL of 70%/16M nitric acid diluted 10:1 with water.

It was mainly the pH reading of .95 that spooked me. I think the straight nitric acid was less acidic (1.65, from what I remember). I kind of envisioned a metaphorical scene in a cheezy action film where somebody finds himself in a pit filled with groggy crocodiles on ice... rapidly melting ice. And really, really hungry crocodiles...

So... do you think the isatin is just in solution with whatever the oily-looking-but-highly-miscible-yellow-orange liquid is, or do you think the Isatin precipitated out, then ended up getting destroyed by continued exposure to the oxidant (like it apparently did with the ozone attempt)?

[Edited on 14-10-2004 by miamicanes]

fermium - 14-10-2004 at 00:46

Indigo plus nitric or chromic acid apparently produces isatin plus anthranilic acid, plus a bunch of other degradation and condensation products.

This is probably why isatin has not been commercially produced from indigo anytime in the twentieth century, because other syntheses are much more practical.

You probably are producing isatin plus a mix of other stuff. To answer the question of what to do next probably have to go back to the original 19th-century German references or other papers based on them.

This project does seem like mad, mad science given that you can buy 100g of isatin online for less than you already spent on the experiment.

http://www.sciencelab.com/page/S/PVAR/10416/SLI1291

Marvin - 14-10-2004 at 04:34

Working with an indigo sludge and adding drop wise is not ideal. More likley to over oxidise, you need a suspension in a large volume of nitric acid and as soon as you start to see any yellow forming stop adding and filter the moment its complete.

How fine a powder is the indigo you are working with btw? Since both indigo and isatin are insoluable I would think youd need a very very fine powder.

You could also think about trying cold very dilute and *neutral* potassium permanganate as an oxidising agent.

I would bet sizable amounts a large fraction of your yellow oil is isatin with enough impurities to render it liquid. Try a purification step.

You dont need to be scared of the nitration mixture exploding, NO2 is the nastiest thing it will do, have good ventillation (and you NEED good ventillation). You're jumpy mainly due to lack of lab experience I think.

Isatin isnt made from indigo industrially because indigo is made from isatin like compounds so its production would be a step backwards. The preperation interest is only historical becuase its how the structure of indigo was determined well enough for chemical syntheses to be devised, before this it had to be extracted at great cost from plants.

I'm wrong about being unable to repair the carbon chain in anthanillic acid without cyanides. Treatment with chloroacetic acid forms phenylglycine-o-carboxlylic acid and then fusion with alkali forms a carbon-carbon bond giveing indoxylic acid. Loss of carbon dioxide from this forms indoxyl which then goes rapidly back to indigo.

miamicanes - 14-10-2004 at 04:53

Quote:

This project does seem like mad, mad science given that you can buy 100g of isatin online for less than you already spent on the experiment.

I tried placing an order from their "other" site (labdepotinc.com) for 500g and got (several days later) an email claiming that it wasn't available and the order was cancelled. I interpreted that as, "we won't sell it to individuals, but don't want to look like assholes so we'll just lie and offer a lame excuse instead."

I'm happy to say that I have found someone apparently willing to sell it, but I'm holding off on dismantling the lab until I have it in my hands. In the meantime, I'd still like to get it successfully synthesized at least once, if only to have something to show for all of my efforts

miamicanes - 15-10-2004 at 23:17

Victory at last! Well... kind of.

I finally got visible, measurable Isatin. That's the good news.

After 4 grams of indigotin, around 5mL of 70%/16M nitric acid, and a little over 4 hours of work (not counting drying time for the filter paper), I ended up with 0.15g/Isatin. That's the bad news.

Well... it's a start. Next time, I'll double the nitric acid and let it work longer. I ended up with a LOT of sludge due to unoxidized indigo.

How I did it:

measured 4g indigotin into pyrex measuring cup (I wasn't about to risk another $8 flask this time around).

Slowly added approximately 5mL of straight 70%/16M nitric acid a few drops at a time until the powder no longer looked blue. In retrospect, it was still quite blue... but it looked greenish brown at the time because of the layer of oxidized indigotin floating on top.

Added 500mL distilled sodium-free water and brought to a rolling boil.

Filtered slightly-less-than-boiling mixture through #2 whatman into buechner funnel and filter flask w/vacuum pump. Prayed to multiple deities that the black ooze wouldn't harden onto the filter or flask and ruin them (it didn't... it stayed soft and mushy & wiped right off at the end.)

cleaned sludge from measuring cup and washed it. poured liquid from flask into measuring cup to cool off.

watched Isatin crystals form along the top of the liquid.

filtered liquid through #2 whatman paper again. Rinsed profusely with distilled-sodium-free water.

Allowed filter paper and isatin to dry. Weighed paper: .5g (but some paper got torn off when scooping it out of the filter funnel using a metal spatula). The paper used to weigh .4g. Giving myself the benefit of doubt for the chunk of paper that was lost, I'll pretend it weighed .35 grams. .5g - .35g = .15 grams.

Now I just need to figure out how to get the Isatin out of the filter paper. I'm thinking about putting it back in the buechner funnel, putting my finger over the bottom hole, and adding a few mL of everclear to see whether I can dissolve the isatin into it that way then drain it.

Success!

miamicanes - 17-10-2004 at 19:19

Having (mostly) gotten over my fear that the reacted solution is going to spontaneously explode, I conducted my most aggressive experiment to date -- INTENTIONALLY seeking to maximize the amount of red in the final product.

Up to now, I was deathly afraid of the red product because I thought it was picric acid. It turns out, the deep-red reacted product is the Isatin.

Procedure:

Added 5mL 70%/16M nitric acid to 1L pyrex measuring cup

Measured 6g Indigotin onto paper scoop, then slowly sprinkled the indigotin powder onto the nitric acid pooled in the bottom of the measuring cup. The initial reaction was pretty violent -- lots of visible gas, deeply blood-red product.

Continued to add powder as reaction settled down until all powder was added to solution.

When reaction mostly stopped, began to slowly swirl the mixture around the bottom of the measuring cup by tilting the cup towards the corner until all sides had a chance to be exposed to the full power of the acid.

Added more acid a few drops at a time and repeated the slow swirling until all visible powder was gone. At this point, I'd estimate that there were about 40mL of intensely orange-red solution.

Added approximately 500mL of distilled, sodium-free water. The red isatin solution instantly solidified and bonded with the remaining traces of unoxidized indigotin into blobs of tarry scum.

Put cup on stove at medium-high heat and allowed to come to a rolling boil. Made initial attempt to stir, but abandoned further efforts because too much tar (and isatin bound up with it) stuck to the plastic spoon and was wasted.

Allowed solution to boil until all traces of red were gone from black tarry blobs.

filtered solution through #2 whatman paper into filter flask. Set filter flask on burner on low heat to keep warm for a few more minutes.

discovered that tarry gunk had hardened and could not be removed from measuring cup. filled measuring cup with water and brought to a boil, then used spatula to scrape now-softened tarry gunk from the measuring cup's sides. Dumped tar-filled water into back yard, then quickly wiped residue from cup with paper towel immediately afterward.

poured liquid from filter flask into now-clean measuring cup. Allowed it to cool for 3 hours. Liquid was orange-red, but didn't have much visible precipitate along the surface. Panicked, but decided to go through with the filtering anyway.

Filtered liquid using buechner funnel with #2 whatman paper back into filter flask (this time, with suction). As I neared the last of the liquid to be filtered, I was relieved to see that lots of it was settled along the bottom of the measuring cup.

Filtered the last of the liquid. Rinsed the measuring cup with distilled/sodium-free water.

Admired the nearly solid coppery film impregnating the filter paper.

Allowed the filter paper to dry for 3 hours, then got impatient and decided to try something different.

Dumped water from wash bottle and replaced it with 151 proof Everclear (cheaper than paying hazmat shipping for ethanol, almost as pure. If Florida weren't so anal retentive and allowed 190+ proof alcohol to be sold, it would have probably been purer...)

added ~20mL everclear to filter funnel (other end over small beaker) and slowly swirled alcohol over filter paper until most of the isatin dissolved into the alcohol and passed through the paper into the beaker below.

I won't know for sure until tomorrow night (when most of the alcohol will have evaporated), but based upon the weight of the beaker, 10mL pure everclear, and the weight of the beaker with 30mL everclear and dissolved Isatin in it, it looks like I now have approximately 2.5-3g/Isatin to play with.