ergot to whatever question

[flipper]

Say if somebody has a bunch of ergot alkaloids like Ergotamine, Ergokryptine, Ergocornine, Ergocristine, Ergine, Ergonovine, can he just do the same as when it's only Ergotamine. Making it LSA or the Lysergic hydrazine. Or do he have to adjust the procedure or something else?

[Rhodium]

First you need to hydrolyze them all to Lysergic acid using aqueous KOH as per the instructions on my page or in Tihkal. Then carry on using any suitable procedure.

[flipper]

Thanks Rhodium  
Somebody can just hydrolize ergocristine in exactly the same way as hydrolizing ergotamine or ergometrine?
And what about the procedure with Hydrazine? Is any Ergot peptide Alkaloïd useable?

[Rhodium]

Generally the same way, yes. Yields may vary if you aren't using a custom tailored procedure for each purified alkaloid though.

Also read

https://www.thevespiary.org/rhodium/Rhodium/pdf/ergot.alkaloids.chem.rev.pdf

and most definitely purify the resulting lysergic acid by column/flash chromatography.

Do not use the hydrazine method if you are serious about trying it out in practice, it is so outdated it isn't even funny.

[flipper]

Thanks Rhodium.

[kreiselmeier]

My fellow bees, I just recived a note from a person who wrote this:


Many years ago I would buy egotamine tartrate around the corner and  hydrolyse like in smith book :

Dissolve 20mg of the alkaloid (previous extraction) in 200ml 1M KOH
in methanol (ie. dissolve 56g KOH pellets in 1L 100% methanol) in a 1L
heavy walled vacuum flask and evaporate the methanol in vacuum at room
temperature. To prevent flask from cooling, thus prolonging the
evaporation time place flask in a pan of water maintained at room
temperature by gently heating or warm water running through. Add 400
ml 8% KOH in water to the residue and boil for one hour .
 Cool, acidify with dilute sulfuric acid and
shake in separatory funnel with 1L ether. Discard the upper ether
layer and filter the aqueous suspension of lysergic acid(I) in
vacuum. Wash precipitate with 20ml dilute sulfuric acid. and so and so on...

And I would get a workable result.

Now I have Ergometrine Maleate and I tried Shulgins synth. first:

A solution of 6.7 g KOH in 100 mL H2O,  magnetically stirred, was brought to 75 °C, and 10 g ergotamine tartrate (ET) added. The reaction mixture turned yellow as the ergotamine went into solution over the course of 1 h. The stirring was continued for an additional 3 h. The reaction mixture was cooled to about 10 °C with an external ice bath, and acidified to a pH of about 3.0 by the dropwise addition of 2.5 N H2SO4. White solids started to appear early in the neutralization; approximately 60 mL of sulfuric acid was required


When I added 10 Gram of Ergometrine Maleate to the solution which was 75 centigrade, it first turned yello, then reddish, then brown like coffee and smelled like caramel.I let it stirr at 75 for 3 H, then:
I neutralised to a ph of 3.Result:  NOTHING, not even after the night in the fridge.

OK, next try:
The classic one, like on top of this page,

I found out, that 10 gram ergometrine maleate does not dissolve in 100 ml 1M KOH Methanol solution, I evaporated
der vacuum anyway and added  200ml 8% KOH

I made the  8% KOH solution  by making a saturated KOH in Water solution and then filled 80 ml of this  in a 1 liter measuring cylinder and added dest. water till I reached 1 liter, hope this was right, but it did work before...
At around 45 centigrade the solution would turn brown, I put the temp at 90 centigrade for 2 hours, then cool, neutralise, but only recive about 2 g of Lysergic acid.

Then I tried Shulgins synth with higher temp, like reflux, Took samples inbetween, no result. another 10 g gone.

Tried the classic one again , this time boiling under reflux for 1 h 15 min got 1,4 g lsa.

These yields are lousy, what am i doing wrong?
I know that ergometrine maleate takes longer to convert, at least that is what otto snow wrote in his book, and since I take 10 ml samples every half hour I belive he is right.
Where can i find a cool synth for ergometrine maleate?  My stock is shrinkin...

[Lilienthal]

The first step of your procedure (dissolve in methanol and evaporate) seems to be completely useless. What do you think is it for? The rest of your lysergic acid may still be in the acidic solution. Maybe you over-acidified? The solubility might be lowest around pH 7.

[kreiselmeier]

My buddy wrote me:

Ok, with the Methanol you are right, it is only used as a solvent  to get the Ergotamine into solution faster.

My ergometrine (Ergonovine maleate) goes into solution rapidly so actually no Methanol is needed.I just didnt want to make a mistake...

In all writings it is stated that you have to acidify usually to a ph of 3.. Ok thats what I am doing , I use 2,5 N H2SO4

Now even during the neutralisation, I do not get any crystals.


But I will do as you said and lower the ph to only  7 and keep you posted.

[Lilienthal]

I'm just guessing, I haven't checked the solubility data yet! Maybe acidify and add acetone?

[kreiselmeier]

My buddy wrote:


I tried another synth from Smith:



A shorter method of hydrolysis which may work as well follows: dissolve 20 g alkaloid in 300 ml methanol and 300 ml 40% KOH and reflux two hours under N2 (if possible). Cool, saturate with CO2 and evaporate in vacuum.

Since I had no CO2 ( I live in the third world) I neutralized with 2,5 N H2SO4 and recived about a 20% Yield of a gooey black  substance I still have to clean...

Will keep you posted!

[neohippy]

use the freebase and heat for only one hour.

[bbell]

I sugest you first start with the free base.Then work up of the method of Jacobs and Craig using methanolic KOH.

[kreiselmeier]

My buddy wrote:

Ok, I tried to isolate the freebase. I therefore dissolved the Ergometrine Maleate in Dest. Water, then added Ammonia sol.25% till ph was 8.5.
The extracted with CHCL3. I extracted again and again and I find that CHCL3 is s a lousy solvent for the freebase. So I tried


Extraktion:
(a.) Methanol + konz.NH3 + Chloroform (9 : 1 : 90),
or
(b.) Methanol + Chloroform (5 : 95),
(c.) H2O + Chloroform (4 :50).
(d.) multiple Extraktion: 2 times  (a.) then once (c.)

still not good at all.

I am now waiting for 1,2 Dichloroethylene(ethylene dichloride) and Trichloro Etylene.

Will let you know how thingsd are going.

By the way, for the german speaking bees around, this forum is not so bad after all: 

http://www.chemie.de/HyperNews/get/forums/chemstarter.html

[Lilienthal]

I does't make sense at all to isolate the freebase and then hydrolyze in KOH / methanol! Under those conditions you automatically get the freebase in nanoseconds.

[Bubbleplate]

Lysergic Acid derivative (LAD) compounds (ergot alkaloids) are weak bases. Arcamone researched the "Partition Coefficients" of LAD's in various solvents and found the following:
At pH 7.5, LAD compounds in water.
Partition coefficients of solvents:
n-Butanol >24
iso-Butanol 14.5
Chloroform-iso-butanol (4:1) 9
Chloroform 3.7
n-butyl acetate 3.7
Methylene Chloride - 3.4
Benzene - 0.3

You'll have better success using a Chloroform-iso-Butanol mixture. Extract with that,(pH 7.5 or then extract the solvent with sulfuric acid water at pH 3.5 a few times.
Make the water extract basic again (pH with dilute hydroxide, then re-extract with chloroform. You may want to add a trace of Versene to prevent deterioration of the alkaloids. (Be sure to do final extract under low light conditions!) Evaporate chlorform under vacuum at no more than 30 C.

Ergot alkaloids are insoluable in petroleum ether or carbon tetrachloride.

[Rhodium]

Do you have a reference for that study by Arcamone?

[kreiselmeier]

My buddy wrote:

I tried to hydrolyse the Ergometrine maleate the same way, as I worked with Ergotamin Tartrate.
With the Ergometrine Maleate I get no results. Only a little black gooey mass.
It is pretty clear, that when I hydrolyse Ergometrine Maleate with KOH, Potassiummaleate is formed by the neutralisation with KOH, which then interfears with the hydrolysis.
So it is advised to obtain the freebase.
Since Ergometrine fb. is soluble in water which has a polarity 10,2  it belive it might be difficult to extract with something which has a lower polarity, like dichloroetane, or CHCL3

But I will try with CHCL3 - iso-butanol and let you know

[kreiselmeier]

So far:

The hydrolysis of Ergometrine Maleate does not work the same way like Ergtamine Tartrate.

The reason for this must be, that the Salt of the Maleate which is formed during the neutralisation, which is taking place when the Ergometrine Maleate is added to the KOH Solution, does interfear with the hydrolysis.

The reason for this is not really clear to me.

I tried to neutralise with ammoniasolution 25% in dry Chloroform,

I recived crystals which had a diffrent meltingpoint from Ergometrine Maleate and would look different under black  light,  but on hydrolysis, again no result.

I tried to neutralise with Ammoniasolution 25% in dry Methanol,

Same result as before. Nothing.

I assume that the neutralisation resulted in a mix of Ergometrine freebase and Maleateamid (?)

Like this maybe?

Maleic acid: CH (COOH): CH.(COOH)  + NH4OH  in H2O  gives                                                                  
NH4C(COOH):CH(COOH) or better NH2CH2(COOH):CH(COOH)  + H2O

or if the doublebond is broken maybe this:

      2 NH2CH2(COOH)  Which is of course not maleate amide   + 2H2O


2NH4OH = 70.0916 MOL
CHCOOHCHCOOH = 116.07216  MOL
 70.0916+CHCOOHCHCOOH = 186.16376 MOL

2H2O = 36.03056 36.03056  +  2NH2CH2COOH = 186.16376 MOL


The 2 NH2CH2COOH  would then in the hydrolysis with KOH, form Potassium maleate (?) again, which spoils the process.

Now one idea ocurred: How about transforming the Maleate amide via electrolysis:
So maybe the remaining salt could be split up by electrolysis to KOH,  H2, H20, CH2NH2 or something which I could evaporate under vacuum or does no harm to the hydrolysis.

On the other side, the ergometrine freebase might be affected, since adding H+ and OH- might protonise the N groups and destroy the peptide bonds

I am just looking for a way to circumvent the ,"extracting with solvent" step, since it seems to be very tedious.

I tried now varius ways to neutralise and seperate the freebase from the "Maleate amide".

Following solvents where used:

Chloroform    - dissolves very little, about 500mg / Liter,
Methanol + konz.NH3 + Chloroform (9 : 1 : 90),  pretty much the same
Methanol + Chloroform (5 : 95), what to say?
Benzene  - nothing
Petroleum ether - nothing
Acetone -nothing

For the rest I am waiting for my other solvents to come.

By the way, China,  is getting tighter, Vietnam not:

The Peoples Republic of China (PROC) is one of the world’s major producers of chemicals including most of the twenty two (22) precursors controlled under the 1988 United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances aside from being a major destination country and a transit point of illegal drugs from the Golden Triangle. The ma huang plant or ephedra (ephedra equisetina) grows wild in northern China particularly in the autonomous regions of Inner Mongolia and Xinjiang. The plant is harvested by villagers and sold to factories for ephedrine extraction, a precursor in the production of amphetamine and methamphetamine. In 1998 alone, 340 tons of ephedrine were produced in China and distributed to almost 31 sales companies and 27 export companies. The Sichuan Province in Central China is also a primary source of precursors diverted to clandestine methamphetamine laboratories in the southwest provinces of Guangdong and Fuchian. Precursors are also smuggled into Laos, Myanmar and Thailand while others are trafficked to destination countries utilizing Hongkong, Malaysia, Singapore, and Vietnam as transit points.
The government controls the importation and exportation of all the twenty two (22) precursors enumerated under the 1988 UN Convention on Drugs. In addition, it also controls other substances that are unique within the country to include palladium chloride, sodium acetate, ammonium chloride, barium sulfate, thionyl chloride, and chloroform. In terms of domestic distribution, the provincial laws of Sichuan, Yunnan, Ningxia, and Guzhau also control all the precursor chemicals controlled by the United Nations.
To further prevent the illegal exportation of precursor chemicals, China has devised an effective control measure by requiring import authorization from the importing country and providing the latter with a pre-export notification to verify the veracity of the import authorization before the precursor shipment is effected. An expert committee has also been established to exercise supervision and provide guidelines in the control of precursors. In addition, a precursor control unit has been established in several provinces to monitor the trafficking of precursors and other controlled substances

[Bubbleplate]

The reference for Arcamone is what is probably the single best paper ever on Claviceps. Arcamone et.al. were the first to culture Claviceps on a large scale and successfuly get Lysergic compounds from liquid culture:
"Proc. Roy. Soc., Ser. B 155, page 26-54, 1961"

[kreiselmeier]

My buddy wrote:

  Ok, this is how far I am:

1,2 Dichloroethane does not disolve ergometrine freebase at all, thank you  neohippy, try again.


same goes for Tetrachloroethylene.

Ethylacetate is a little better. It does dissolve the freebase but only very limited, so for extraction not recommenable.

Dichloromethane now, well it seems to me, that this is the only solvent worthwhile. Not that this one is overwhelmingly good, but the best so far.

I guess I will use a Soxhlet extaction in the future, just to save solvent, since when I evaporate in Vacuum, I loose about 50 to 80% and I want to extract some of this stuff, this means much of solvent, no I better stick to Soxhlet.

Oh yes, when I add NH3 to basify the base stays untouched. Just the maeate and the freebase split, no new molecule is formed.
So I just have to isolate the freebase from the maleate, which is, since they are both so watersoluble, a tricky task to do.
.