How would one convert 2-Bromo-Paspalic acid into Paspalic acid?
I've searched the literature for this, or similar reactions, but couldn't find anything.Sauron - 21-12-2008 at 20:58
Never heard of paspallic acid, what is the structure?BobHawson - 21-12-2008 at 21:38
Sauron - 21-12-2008 at 22:58
So much for the structure of the parent acid. So you want to dehalogenate the 2-Br derivative without affecting anything else.
Where is the 2-position on this polycyclic system? This is an a,b-unsaturated acid. If the 2-position is the beta site and the bromo derivative is
saturated then getting the Br to eliminate and form that conjugated pi bond ought to be easy. You just need to find a mild reagent (base likely) to do
the job selectively.
Google never heard of paspallic acid either.
ACS search engine returns 86 hits for 2-bromopaspallic acid all centering on marine ecology and oceanic biochemistry.
[Edited on 22-12-2008 by Sauron]stoichiometric_steve - 22-12-2008 at 03:32
Quote:
Originally posted by Sauron
Google never heard of paspallic acid either.
because it is spelled PASPALIC ACIDSauron - 22-12-2008 at 04:59
Well, since the very first hit on Google under that spelling is SYNTHESIS OF LYSERGIC ACID FROM PASPALIC ACID
... I am out of here and I suggest a moderator take note.Nicodem - 22-12-2008 at 06:21
Please do not open threads without providing at least a minimum of references, unless in the Beginnings section! I will be moving this kind of threads
there anyway, so what is the point of not opening them in Beginnings in the first place? Also, use the search engine before posting.
[Edited on 22/12/2008 by Nicodem]sparkgap - 22-12-2008 at 07:33
From the third post, it was clear that he wanted to fiddle with ergot alkaloids.
Surely not for parturition purposes, good sir?
sparky (~_~)BobHawson - 22-12-2008 at 11:26
How to off the bromine atom here:
[Edited on 22-12-2008 by BobHawson]harrydrez - 22-12-2008 at 14:37
Quote:
Originally posted by sparkgap
From the third post, it was clear that he wanted to fiddle with ergot alkaloids.
Surely not for parturition purposes, good sir?
sparky (~_~)
He wants to cure his migraines, funny, third post was like a neon sign screaming "LSD!"Trifluoroacetic - 22-12-2008 at 17:38
print out the image and cut off the Br with a pair of scissors and you will have what you need.Sauron - 22-12-2008 at 17:50
He does seem truly lost and forlorn, doesn't he?
Try searching 2-bromoindole and seeing how to debrominate that You do not however want to reduce that double bond. You want to replace Br with H,
that' all. And that's a clue.JohnWW - 22-12-2008 at 19:49
Paspalic acid? It must be connected with the Paspalum genus of grasses, from Africa, which are good in pasture for grazing by livestock, but terrible
in lawns because of their seed-heads which are sticky when ripe. They are very common here in New Zealand.
So its structure is related to that of ergotamine and LSD? Perhaps it is formed on paspalum seed-heads if the ergot fungus gets at them, similarly to
rye. Both of the Ns, and two of the C atoms, are optically active.
[Edited on 23-12-08 by JohnWW]Sauron - 22-12-2008 at 20:42
The stereochemistry is pretty daunting, the total syntheses are daunting, the really hard part is making this stuff without autointoxicating, which is
a lab environment is pretty hazardous.
I do not think the thread author is in any real danger of getting to that point, however.
Google still barfs on 2-bromopaspalic acid, no hits at all. Is this perhaps a medicinal ergot derivative? There are lots of those used for migraines
and so on, also in obstetrics. Ergotamine tartrate being the best known, and probably most common precursor to the recreational derivative.
I was once sitting in the office of US Customs Investigations chatting with a pal there and they had just caught a fellow on a currency violation with
$25,000 cash that he failed to declare, and on him was a list of chemicals to buy in his destination (Italy). and since I am a chemist they showed me
the list. Top item: A Kg of ergotamine tartrate. I laughed out loud.
AFAIK paspalic acid is just another hydrolysis product of ergot alkaloid(s) and is produced industrially by same methods as lysergic acid, i.e.,
fermentation of appropriate fungi, Claviceps in particular.
So far I have seen nothing about 2-bromopaspalic acid anywhere, and am only looking desultorily out of curiosity as to what the thread author is on
about.
[Edited on 23-12-2008 by Sauron]zed - 23-12-2008 at 23:45
Geez, is it cheap? If it is, you could try refluxing it with a little Potassium Hydride. That might work.
Gotta be careful with molecules like that though. Might isomerize, might react adversely to light, might accidentally become lysergic acid...Sure
does resemble it.
At any rate, such chemistry is extra-ordinarily arcane. This one is probably up to you to figure out. A few hours, days, weeks, or possibly years,
in a good research library, should give you the information you desire.JohnWW - 24-12-2008 at 00:25
To elucidate on my previous post, http://en.wikipedia.org/wiki/Paspalum , which lists the various species of the paspalum genus, says "Claviceps paspali is a Claviceps sac fungus
that grows on Paspalum, producing ergot alkaloids and the tremorgen paspalitrem; it causes "paspalum staggers" poisoning in cattle." That must be what
gives rise to paspalic acid in ripe paspalum seed-heads. The paspalum genus is of tropical or subtropical American origin.
The species of paspalum used for pastures in New Zealand, which is also an undesirable lawn weed because of its clumping habit and tall seed-heads, is
paspalum dilatatum; see http://www.yates.co.nz/problem-solver/problems/paspalum/ and http://www.finelawn.co.nz/index.asp?PageID=2145839048 and http://www.rnzih.org.nz/Plant_Doctor/Paspalum.htm . It can be controlled using Roundup (glyphosate). Also found in New Zealand is paspalum
vaginatum, which resembles bermudagrass but has a higher salinity tolerance, being in fact used for low-lying golf courses etc.. Another introduced
weed species in New Zealand, of no agricultural use, is mercer grass, paspalum distichum, also known as water couch or knot grass, and which requires
even stronger herbicides than Roundup for control.Sauron - 24-12-2008 at 00:37
John, since the ergot fungus of interest is Claviceps paspali and the grass is paspallum, the question is which is named for what, taxonomically? But
irregardless, the connection is clear. Equally clear is that the ergot fungus is not confined to central europe as Merck Index would have us believe,
but present in Africa, parts of the Americas and possibly NZ and Australia as well.
zed, I seriously doubt that any ergot alkaloid hydrolysis product is cheap. And that is what paspalic acid is, and therefore what 2-bromopaspalic acid
is derived from. KOH is known to isomerize PA to LA and ILA and the latter is particularly undesirable. There is a patented workaround involving a PTC
with ot without a small amount of alkali metal hydroxide, as discussed ad nauseam on the usual suspect websites. The primarily lit. is in Helvetica
Chem Acta as you might expect.
The classic Woodward total synthesis of lysergic acid is very long (16 steps). A shorter rather elegant route emerged in Synlett 1994 p 487-489
starting from 4-ethynylindole-3-acetonitrile. That compound is available from 4-bromoindole. The tetracyclic ergoline skeleton os constructed in a
single step employing a cobalt-cyclopentadienyl catalyst and a suitably substituted alkyne for 4 + 2 cyclization to a b-pyridine annelated product.
The procedure is technique intensive, yields are moderate, and the products are 4-component mixtures that require chromatographic seperation. But
still, beautiful work, and this is all chemistry and not microbiology as is usually the case. Racemic LSD tartrate was prepared in seven steps from
4-bromoindole and overall 11% yld. Still would need resolution but that can be done enzymatically (papain) since it is an amide.
Maybe this approach has been improved since 1994?
Sorry about the crappy scan, that's the way it is on my Synlett archive from References.
[Edited on 25-12-2008 by Sauron]
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Sauron - 24-12-2008 at 22:23
Since the pdf is so muddy I have redrawn scheme 2
R = H, Me
For R1 and R2 see pdf. For catalyst see references. Looks like a cyclopentadienyl comples with a cobalt carbonyl, what fun!
The indole reactant is compound 5, the alkyne is 2, the products 6,7,8,9. 8 and 9 arise from air traces in reaction. 6 and 7 are main products due to
failure to achieve regioselectivity and tendency of R1 to hydrolyze when vicinal to N. For ring numbering and identification of rings A-D see pdf.
[Edited on 25-12-2008 by Sauron]
Sauron - 25-12-2008 at 01:27
4-ethynyl-3-indoleacetonitrile may look exotic but it is readily constructed from 2-bromo-6-nitro-(2-dimethylamino)styrene.
The indole ring is formed with Fe powder, acetic acid and silica gel in benzene/cyclohexane.
Aqueous dimethylamine 40%, 37%formalin and acetic acid add at the 3-position
KCN in aqueous DMF converts the teriary amine to indole-3-acetonitrile.
Finally trimethylsilylethyne is added at the 4-bromo site and the TMS group removed with PPh3I2, PdCl2 abd 3% CuI in TEA under autogenous pressure for
18 hrs.
See scheme and references in pdf posted above. Yields are high.
[Edited on 25-12-2008 by Sauron]
[Edited on 25-12-2008 by Sauron]
Sauron - 25-12-2008 at 05:32
Timethylsilylethyne (TMS-acetylene) is made, per Org.Syn., from n-butylmagnesium chloride in THF reacted with acetylene gas and then the acetylene
Grignard reagent reacted with trimethylsilyl chloride.
Monograph pdf attached.
I am scratching my head opver the starting material. A beta-dimethylaminostyrene? A (2-dimethylamino)phenylethene? Any suggestions as to nomenclature
and preparation, anyone?
how about 1,2-styrenediol (styrene glycol)?
Chlorinate the 2 position, slap a dimethylamino group on there and dehydrate that benzylic hydroxyl?
Ring nitrate it and isolate the 2-nitro product, and monobrominate last.
May have to block the 4-position with a sulfonic acid to preclude dibromination, maybe do that before the nitration.
Hmmm.
[Edited on 25-12-2008 by Sauron]
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zed - 25-12-2008 at 12:41
My 14 year-old grand daughter tells me that when she and her friends need Lysergic Acid, and her Swiss chemical broker can't get them Ergotamine,
because he is in prison again...... They simply resort to the Hendrickson-Wang Synthesis.
Embarrassingly, the entire paper is posted on that nasty Rhodium site, but it is hard to find elsewhere. Hard to find for free, at any rate.
Could my beloved little Munchkin-kiss, be headed down a perilous path?
[Edited on 25-12-2008 by zed]crazyboy - 25-12-2008 at 13:27
I can't tell if your joking but if you have a 14 year old granddaughter making lysergic acid you need to enroll her in some sort of program (organic
chemistry not drug rehab).
From what I can tell lysergic acid is very delicate and atmosphere, light, moisture etc will destroy. Also from a practical standpoint i would assume
all indole based compounds are restricted.Sauron - 25-12-2008 at 14:22
I think zed said something very similar about the fragility of this structural class upthread.
Thanks, zed, very interesting. A decade fresher than the paper from SynLett, I guess we are creeping up on the state of the art.
Both routes, though very different, share 4-bromoindole as one of the key precursors. The 1994 prep is like falling off a log, while the 2004 prep
uses TFA and thallium trifluoroacetate. TFA is merely aggressive and unpleasant even in a hood, thallium salts are megatoxic. I will need more time
before I can comment further about the relative merits of these two routes. But very interesting indeed.
Oh, by the by:
the thread author was asking about 2-bromopaspalic acid.
See the Merck Index for bromolysergide. That is bromo-LSD. Inhibits serotonin but devoid of hallucinatory effects.
My guess is that a bulky Br vicinal to the indole N lone pair blocks interaction with receptor sites for those effects.
So I suppose thread author wants to remove Br at C2 so he can convert to LA. No surprise.
----------------
Thallium triflate is also horribly expensive. Over $50/g and 30 g are used in prep in the Org.Lett. paper.
The indole ring is readily built from 2-nitrotoluene using ethyl oxalate. See Org.Syn. The resulting 2-ethylindole carboxylate is readily hydrolyzed
and decarboxylated. What is wrong with doing same procedure to 6-bromo-2-nitrotoluene? Or 6-iodo-2-nitrotoluene?
[Edited on 26-12-2008 by Sauron]chemrox - 25-12-2008 at 19:40
So, can't he make the Grignard reagent and hydrolize it? Or is paspalic acid too delicate? And is there a commercially available 2-Br-paspalic acid?Sauron - 25-12-2008 at 21:00
The answer to all is "Who knows?"
I have yet to find any reference ro 2-bromopaspalic acid.
I do not have a clue how fragile it might be. I would expect the Grignard to potentially react with the carboxylic acid site though.
--------
There are lots of indole preps in the lit. and surely several will allow starting with a ring Br that will survive under reaction conditions.
The 1994 SynLett paper uses Fe powder and AcOH in benzene/cyclohexane to cyclize 6-bromo-2-nitro-(2-dimethylamini)styrene to 4-bromoindole.
There are half a dozen generally similar reactions in Org.Syn.
Back in the Melatonin thread I looked at a few of these.
It's just a matter of jumping back into indole chemistry and finding ane answers. 4-Bromoindole is commercially available but outrageously expensive.
Our target is 4-bromoindole.
Here's an Org.Syn prep to a 4-chloro-5-azaindole-2-carbomethyl ester.
They start with 2-chloropyridine-3-carboxaldehyde. I would just substitute 2-bromobenzaldehyde, or 2-iodobenzaldehyde and follow their sequence from
there.
The aldehyde is reacted with ethyl azidoacetate (from ethylbromoacetate and sodium azide) which is readily cyclized to the indole, and I know that the
methyl ester is easy to hydrolyze and the acid group at 2 position decarboxylates. Voila. 4-haloindole. No TFA, no thallium (III) triflate.
[Edited on 26-12-2008 by Sauron]
[Edited on 26-12-2008 by Sauron]
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Ozone - 25-12-2008 at 21:39
Your right, P487 is nice work!
Normally I will try to avoid threads like this, but I am curious (mechanism-wise) about the heat + hv. I have seen product distributions like this
with truxillates/truxinates (compromising between thermal and photochemical routes). It would appear that careful optimization of temperature while
the radiative wavelength and flux are fixed (or vice-versa) might give a tuned reaction yielding only two products, one of which in excess?
Immobilizing one of the reactants on a solid phase comes to mind. The concept might be applicable to more interesting (and legal) targets.
Cheers,
O3
Hemetsberger-Knittel Anyone?
Sauron - 26-12-2008 at 04:31
Here is reaction scheme for the easiest indole prep I have ever seen.
If one simply must kvetch, the bromoacetates are nasty lachrymators. But other than that I see little wrong with this short sweet prep.
It is clearly related to the prep employed in the 1994 SynLett paper posted above.
[Edited on 26-12-2008 by Sauron]
Sauron - 26-12-2008 at 05:47
Another look at that precursor in the 1994 SynLett paper (see upthread)
Might not this be the product of base catalyzed condensation of a benzaldehyde with DMF?
If so then the real starting material is 2-bromo-6-nitrobenzaldehyde.
And this one rather than the Hemetsberger-Knittel abovethread, takes pride of place.
In both cases the reaction is between benzaldehydes and a carboxylic acid derivative. On the one hand an ester of a substituted acetic acid, on the
other hand, a formamide (formic acid amide).
NOTE: My speculation was close but not quite perfect.
The ref.7 in SynLett 1994 eventually led back to three papers in a series in Chemical & Pharmaceutical Bulletin, open access English language in
Japan.
The substrate is a substituted nitrotoluene and the reagent, DMF-DMA, dimethylformamide dimethyl acetal. This reacts in DMF as solvent to give 90% of
the enamine and the enamine is easily cyclized to 4-substituted indole. See the scheme and three posted papers downthread.
[Edited on 27-12-2008 by Sauron]
not_important - 26-12-2008 at 08:37
If I was going to kvetch, it would be about the N3 group rather than the bromo-acetate. The words This reaction should be performed behind a
safety shield are more worrisome than need a fumehood. Useful when dealing with the pyridine instead of benzene ring, as the
heterocycle is more difficult to deal with than the benzene, with many of the normal routes to indoles not working well. The nitro-benzaldehyde/DMF
would be easier if one were after the vanilla indoles.Sauron - 26-12-2008 at 16:00
Well, I saw that warning, but evaluated it as pro forma, given that no explosions were reported. the azidoacrylates are unstable, and tend to evolve
N2 slowly while you watch. In one example with a different substrate, the reaction mix frothed out of the pot. None of that seems very nerve wracking
to me.
When I was a RA in the 70s there was a postdoc in the same group who was making a series of small ring N-heterocycles, and used a lot of NaN3. His
products often detonated (or deflagrated) in the drying oven. So I have been around azides, and am not easily intimidated. I have also been around
long enough to know when Org Syn's editors are crying wolf for fear of liability lawsuits.
All that being said, now that the light bulb has gone on and I realized DMF is the answer to that other precursor, I agree that it is the better way
to go. Thanks for the comment.BobHawson - 26-12-2008 at 16:27
First of all, thanks for all the interesting discussion.
Second, does anyone have thoughts on removing the bromine of bromocriptine to leave you with ergocryptine?
I've read that this would entail making the Grignard of bromocriptine, then hydrolyzing it off leaving a hydrogen in its place. Would doing this
likely case side reactions?
I don't think this warrants a new thread as its so close to the starting subject, so I asked here.
[Edited on 26-12-2008 by BobHawson]BobHawson - 26-12-2008 at 16:41
Quote:
See the Merck Index for bromolysergide. That is bromo-LSD. Inhibits serotonin but devoid of hallucinatory effects.
My guess is that a bulky Br vicinal to the indole N lone pair blocks interaction with receptor sites for those effects.
[Edited on 26-12-2008 by Sauron]
Which receptor sites do you mean? It seems to affect serotonin receptors.
BOL-148. 2-Bromo-N,N-diethyllysergamide.
At 6 to 10 milligrams orally, there are some mental changes noted. But in another study, 20 milligrams was administered a day to a subject for 7 days,
and there were no reported effects. And yet it is as potent a serotonin agonist as is LSD.
taken from http://www.erowid.org/library/books_online/tihkal/tihkal26.s...
Apologies if posting from books is against forum rules.
[Edited on 26-12-2008 by BobHawson]Sauron - 26-12-2008 at 17:16
Posting from books is not at all prohibited but it is customary to cite sources.
I simply meant, whatever receptor sites are involved in the hallucinatory effects, which the 2-bromo derivative does not posess. But the parent
compound does. I speculated that a bulky substituent vicinal to the N at 1 might sterically hinder interaction. But this was merely idle speculation,
I know nothing of the neuropharmacology of these substances.
Is 2-bromo-PA commercially available? Another member wanted to know.
See upthread re:Grignard and hydrolysis and possible side reactions. Posting the structure of bromocristine would be helpful.
Ergocristine is another ergot alkalois fragment that has been exploited clandestinely as a precursor to LA and LSD. The others that come to mind are
ergotamine, elymoclavine, ergotinine, and paspalic acid. Are we going to discuss them one by one in terms of the 2-bromo derivs, or should we cover
them as a class?
Oh, and that list is far from exclusive.
-----------------------
I tracked down that indole prep talked about in Synlett 1994, they referenced a paper (ref.6) from Chem.Pharm.Bull. which is open access. The SynLett
procedure was modified from the Japanese one, and I needed to go two papers back in CPB to volume 29 to find the details.
The Japanese authors prepared 4-nitroindole and 4-aminoindole by the titanium(III) chloride reduction (in aqueous AcOH) of the enamine formed from
2,6-dinitrotoluene and dimethylformamide dimethylacetal. Thus 2,6-dinitro-N,N,-dimethyl-trans-beta-styrene is cyclized to the 4-substituted indoles.
Anhydrous DMF is solvent for the prep of the enamine, 90% yield.
The Synlett authors substituted (apparently) 2-bromo-6-nitrotoluene in the enamine prep, and used Fe powder in AcOH rather than TiCl3 as reducing
agent.
Dimethylformamide dimethylacetal is commercially available.
So this route just got easier. The requisite nitrobromotoluene will be easy to prepare from o-bromotoluene nitration or bromination of o-nitrotoluene.
Doubtless there is lit. on this.
The Japanese authors also got to the 4-halo indoles via diazotization of 4-aminoindole.
I will assemble the CPB articles into a single pdf and post here.
[Edited on 27-12-2008 by Sauron]BobHawson - 26-12-2008 at 20:17
Next time I'll mention what book it was from, but I did give a link to the book.
2-bromo-PA is not commercially available, however 2 Bromo alpha ergocryptine (bromocriptine) is.
I posted a hyperlink to the structure of bromocriptine, and asked how to replace the Br with an H to get ergocryptine (which I also gave a hyperlink
for).
I'll post the actual pictures though.
Bromocriptine
Ergocryptine
We ought to cover them as a class, I think, unless there are significant differences.
And ergocristine. I assume bromocristine would have a bromine in the same postion as bromocriptine
Sorry if its all a bit confusing!
[Edited on 26-12-2008 by BobHawson]Sauron - 26-12-2008 at 20:55
Assuming that the Br are all at the indole C-2 then your problem remains very much the same as with PA. Find a base or reducing agent that will
replace Br with H and not affect anywhere else on the structure. Given the diversity it may not be same reagent for all.
Some experimentation may be called for.
--------------
The Japanese papers are rather large so I will post them one by one in order of publication.
[Edited on 27-12-2008 by Sauron]
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Sauron - 26-12-2008 at 21:23
The Chem Pharm Bull paper last post centers around use of this enamine for prep of 4-substituted indoles.
The authors used TiCl3 in wet AcOH to close the indole ring. They also used Zn/Hg amalgam as an alternative.
In subsequent work (SynLett 1994 posted above) others employed the same enamine reagent with 2-bromo-6-nitrotoluene and also substited Fe powder, AcOH
and silica gel for the reduction/cyclization.
[Edited on 27-12-2008 by Sauron]
BobHawson - 26-12-2008 at 21:27
What bases or reducing agents do you all think would be applicable?
NaOH or KOH seem to be likely candidates. Would they likely work well?Sauron - 26-12-2008 at 21:39
Quote:
Originally posted by BobHawson
What bases or reducing agents do you all think would be applicable?
NaOH or KOH seem to be likely candidates. Would they likely work well?
Not in cases like paspalic acid. They may remove the Br but will also isomerize the structure to lysergic acid with a large (too large) amount of
isolysergic acid as well.
According to the patent literature, a quaternary ammonium base (PTC) is used to get the isomerization without the epimerization. Will this reagent
also take off your Br? I do not know. The answer is in the lit. somewhere, and if not, you need to experiment. I don't think anyone on this forum has
this answer in his head, nor are they likely to want to spoonfeed you even if they do. But, I could be wrong.Sauron - 26-12-2008 at 21:41
The intermediate followup paper from Chem Pharm Bull vol 29
[Edited on 27-12-2008 by Sauron]
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Sauron - 26-12-2008 at 21:45
The third and final of the CPB Japan papers on prep of 4-substituted indoles
This also covers building of the 3-acetonitrile side chain on such indoles as requisite for the unrelated work in SynLett 1994.
BTW this reaction is called The Leimgruber-Batcho Indole Synthesis
There's an Org.Syn. monograph by Botcho and Leimgruber on this reaction.
I found a JOC paper on it as well, using the Fe powder/AcOH reducing system as in SynLett
And the Org.Syn. paper references a Ber. preparation for the DMF-dimethylacetal. Wiley's server is down but as soon as they get their act together I
will get the DOI for this and request it in References.
[Edited on 28-12-2008 by Sauron]
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BobHawson - 26-12-2008 at 22:03
Thank you for the literature, will make for interesting reading.
What about in the cases of bromocriptine and bromocristine?
NaOH or KOH would take off the bromine, but I assume they would also hydrolyze off half the molecule in the same reaction. It seems they would leave a
mix of LA and predominately iso-LA.
Now how would one just remove the Br without hydrolyzing off the other portion of the molecule?BobHawson - 27-12-2008 at 10:07
I haven't, could you post it or give a link to it?Sauron - 27-12-2008 at 10:09
I have dug up four last papers to tidy up loose ends re prep of 4-bromoindole.
Here are the first two:
-- a review of the Leimgruber-Batcho indole synthesis
I assume you mean Stoll?Sauron - 27-12-2008 at 20:29
Good assumption.
Here are the last 2 papers dealing with the prep of 4-bromoindoles:
-- Org Syn prep by Batcho and Leimgruber for whom rxn is named
-- a JOC note describing the use of Fe/AcOH as the reducing system for cyclization in this reaction
I compiled these into a rar for convenience
[Edited on 28-12-2008 by Sauron]
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Sauron - 28-12-2008 at 16:47
The enaminating agent in the Leimgruber-Batcho indole synthesis is, as already discussed, DMF-DEA and I posted Broderick's prep of this which employs
dimethyl sulfate.
Subsequently I found my copy of Paquette's book and extracted the section on this type of reagent, which includes two additional preparations, one
using chloroform and the other, the Vilsmeier reagent. Yields are not as high as reported by Broderick, not no nasty old dimethyl sulfate involved,
and for many of us that is a good tradeoff.
Also this paper describes many of the other reactions of this versatile and powerful orthoamide.
[Edited on 29-12-2008 by Sauron]
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zed - 7-1-2009 at 12:34
As I recall, producing iso-lysergic acid isn't a terminal problem. The isomerization is reversible. Iso-lysergic acid may be isomerized back into
lysergic acid without too much fuss.Sauron - 7-1-2009 at 19:55
That's true because LA and iso-LA are epimers.
That happy situation is not the case for D-LA vs L-LA. Which is to say (+)-LA vs (-)-LA. The Wang-Hendrickson produces racemic LA,
an equal mixture.
However as I am not going to make LA or any of its derivatives, this is not my problem.
