From Pepper to MDA experiments

[pHarmacist]

Wouldn't KMnO4 oxidize piperine directly to Benzo[1,3]dioxole-5-carboxylic acid? According to my org chem book, it doesen't metter how long the carbon chain (of alkene) is, KMnO4 will cleave it allways at benzyl-carbon to give corresponding carboxylic acid....




1-2-3 ACiD

[Rhodium]

Under basic conditions, KMnO₄ is not as strong as it is under neutral or acid conditions, and the selectivity is increased. Cooling, and the addition of MgSO4 to the reaction mixture also helps. There are examples of this at my page, where propenylbenzenes (like asarone) is oxidized to the corresponding benzaldehyde.

What I don't understand though is how you suggest that LAH can be used to reduce a carboxylic acid to an aldehyde.

[pHarmacist]

Scroll down to "Reduction of Acyl Compounds Using Various Reducing Agents" on this page:

http://members.aol.com/logan20/ald_syn.html

and you'll see carboxylic acid reduction with LiAlH to aldehyde (a)

I know that most common method is via acylchloride... but after coming across the above described possibility, I figured, why not? Of corse, it can be errorous...

1-2-3 ACiD

[Rhodium]

I've never seen that before. It seems to me it would be very hard to not overreduce to the alcohol.

[pHarmacist]

I know, it looked wierd to me 2, since i know that LAH will continue reducing no matter what... strange... it could be an error on that page huh?
1-2-3 ACiD

[Rhodium]

At least an additional reagent or other vital information is left out. It is not possible to do using standard methods.

[hCiLdOdUeDn]

Can someone confirm that copper sulfate under basic conditions would oxidize piperic acid into piperonal with higher yields then KMnO4?

The method seems simple. Just throw in your piperic acid, NaOH, CuSO4, and water. Reflux for 8hours, then filter through a buchner funnel, wash the filter cake, and acidifiy filtrate with HCl. Then extract with DCM and remove DCM to leave impure piperonal crystals? Is that method doable?

If the DCM contained unreacted piperic acid or piperidine, and piperonal, then couldnt a bee do a bisulfite adduct to purify piperonal purification??

Seems like a good route if one cannot find safrole!
Sink or SWIM

[Antoncho]

Can someone confirm that copper sulfate under basic conditions would oxidize piperic acid into piperonal with higher yields then KMnO4?



Well, that's a strange question - go ahead, try this yourself and post the results!

It IS very easy.

BTW - you can PM me for help if you ever get to this in practice.




Antoncho

[hCiLdOdUeDn]

And I WILL! Piperine---> Piperonal via CuSO4 experiments coming within the next two weeks....
Sink or SWIM

[Antoncho]

And, to make the road easier for you, let me give you a coupla advices (just in case you don't know):

a) DO NOT try to perform oxidation directly on piperine, hydrolyze to acid 1st. The thing is, in chemistry, ESPECIALLY when you're travelling on an unexplored ground, nothing ever works the 1st time you do it - no matter how simple it seems  To get a positive result, you have to derive conclusions from the preceding negative results, and with piperine no negative result you get (i'll promise you negative results ) will bee conclusive - there's just too many variables involved.

Only IF you succeed in pulling this w/piperic acid, you might want to try this w/piperine - in fact, that would bee a great idea IF you succeed.


b) Don't try to modify the hydrolysis procedure. That piperinic amide bond is very hard to break - bee sure to use KOH (not NaOH) in MeOH or EtOH.

c) Search for the best piperine extraction techniques - there's been posted quite a number of it, decide which one to use depending on your most available solvt. I might add that acetone works well too - if you just leave it in a bottle to SLOWLY evaporate, piperine will xtallize out as beautiful needles.


To all said above i want to add that you may always count on my help in your experiments, if you should need any



Antoncho

[hCiLdOdUeDn]

First off, If something is chemically wrong here its because I am teaching myself organic chemistry.

I have been researching using Benedict's reagent for synthesis of piperonal from piperic acid. But upon reading it seems Benedict's Reagent is used only to oxidize aldehydes into carboxylic acids. 

You would have to reduce piperic acid into piperonal by removing an oxygen, not oxidize it.

I have been reading the post

Post 293365

(Antoncho: "Double bond ox. cleavage (to aldehyde) with CuO", Chemistry Discourse) on the oxidation of vanillin to its aldehyde, but the bonds on vanillin and piperic acid are different. I cant seem to figure out if Benedict's Reagent is oxidizing or reducing.



If Benedict's Reagent wont work to reduce piperic acid to piperonal then could you use al/hg to reduce?

Again, forgive me If I totally screwed up on the oxidation/reduction reactions.

[Rhodium]

the oxidation of vanillin to its aldehyde

That makes no sense, vanillin is already an aldehyde (3-Methoxy-4-Hydroxybenzaldehyde).

The conversion of piperic acid to piperonal is an oxidation, as you are adding an oxygen atom on each of the carbon fragments you create in the reaction (one on the piperonal, and one on the remaining carbon chain (you can disregard the "acid" part of piperic acid, that end of the molecule is not participating in the reaction).

[hCiLdOdUeDn]

I really need to learn more organic chemistry!!

Thanks a bunch for clarifying this for me!

[SPISSHAK]

Starting with alanine, you can oxidize to a nitro acid using potassium permanganate, you then decarboxylate the nitro-acid to nitroethane by forming a sodium ester of the nitroacid and heat this with water, the result is nitroethane and an alkali bicarbonate on reaction with water, I wonder if it would be smarter to acidify the mixture of alanine/KMnO4 and water to more effectively oxidize the amino acid to a nitroacid? Aurelius came up with this idea and it's posted as such:
Method 18:  Oxidation of alanine with permanganate followed by decarboxylation

Nitroethane via oxidation of alanine? 
 
 Theory
------
MeCH(NH2).COOH + 3(O) --> MeCH(NO2).COOH + H2O.
MeCH(NO2).COOH + NaOH --> MeCH(NO2).COONa.
MeCH(NO2).COONa + H2O --> MeCH2(NO2) + NaHCO3.
Procedure
---------
A solution of potassium permanganate (0.3 mol) in water was made by dissolving 47.41 g KMnO4 in 400 mL hot water in a 1 L 3-necked flask fitted with a reflux condenser, a stirbar[note 1], thermometer, and a 100-mL addition funnel. As the solution cools to room temperature fine crystals of KMnO4 crystallise out of solution[note 2]. A solution of alanine (0.1 mol, 8.91 g) in 65 mL of water was placed in the addition funnel and added dropwise with stirring over a 20 minute period. The temperature slowly rose. When the addition was complete, the reaction mixture was heated to 60º over a period of approximately 2 hours. 40 mL of acetone was added [note 3] and then the reaction mixture maintained at 70-85º [the sludge was extremely viscous and the stirbar was of no use] for 2 hours. 0.1 mol sodium hydroxide in 20 mL of water was then added through the addition funnel.
Pause (to be completed).
-----
The flask showed no sign of heating up after addition of the NaOH. By now the black/brown sludge will not mix (with the stir-bar). The next step is to heat to 80-100C to
decarboxylate any nitro-propionic acid and then to steam distil.
Notes:
------
1. An overhead stirrer is essential - the stirbar will get clogged with MnO2.
2. KMnO4 solubility is 1 in 3.5 parts of hot water and 1 in 14 parts of cold water.
3. The acetone was added to try to clear the sludge. I would have added more but I had second thoughts.
Refs:
1. Synthesis Of Aliphatic And Alicyclic Nitro Compounds; Org. Syn. p 131-132 [The Oxidation of Amines]

Post 238118

(Aurelius: "Re: What can be done to improve the performance of clandestine nitroethane synth?", Chemistry Discourse)

[hCiLdOdUeDn]

Hmm.. alanine. Where can I get this OTC?

I am still doing the pepper-->piperonal experiments. After more reading, I have found alot of sources confirming piperic acid does oxidize to piperonal (not like I didnt believe you Rhodium...I DID...I just needed proof   ).

Today Ive just processed oleoresin from blackpepper. This stuff is cool. From reading its a matrix of turpenes and about 70% crystalline piperine. The hard part is isolating the piperine from the turpenes and oil...but after experimentation 10mL of boiling 70% Isopropyl alcohol to 7g of oleoresin produced 5g of crude piperine after cooling the IPA. Letting it stand for 48hours left a layer of nice dark yellow crystals. After recrystalization from ethanol...little clear yellow crystal shards weighed out at approx 4g.

Im going for the route from post

Post 293365

(Antoncho: "Double bond ox. cleavage (to aldehyde) with CuO", Chemistry Discourse) from Antoncho. Hopefully, piperic acid can be oxidizied into piperonal.

Im trying this at a smaller scale. This is my plan (which will be performed VERY SOON):

5g Piperic acid
25.6g Hydrated Copper Sulfate
16.9g Sodium Hydroxide
205g H2O

This will be placed in a 500mL RB flask refluxed for 8hours with good magnetic stirring.

After the solution cools, I vacuum filter it. This should leave precipatated red cupric oxide because the action of the Benedicts reagent oxidizing the carboxylic acid into the corresponding aldehyde. I will wash the cupric oxide through the filter with warm ethanol and add this to the mother solution.

After that I throw everything into a 1L sep funnel and acidify until neutral. I then extract 3x 50mL DCM. Pool the DCM and evaporate to leave something....

Perhaps bisulifte/metabisulfite could purify piperonal. Destruction could be done with sodium carbonate or NaOH.

These are just thoughts. Anyone care to mention a better idea?

I know it probably needs alot of tinkering before it can work but does piperic acid need to be in suspension or does it need to be dissolved in the solution to work?

[Aurelius]

Hey Spisshak, thanks for the credit, but aurelius did not come up with the idea for the alanine oxidation procedure.  I found that in a search of the older materials on the hive. I can't remember who the credit goes to, but if you do a search i'm sure it'll be easy to find.  I did a search, Cherrie Baby was the original poster.  credit goes to CB. 


BTW: alanine is sold all over the internet and in health stores such as G*C.

[odin]

SPISSHAK, please complete  and post the experiment, EtNO2 from alanine, GREAT !!!!

[moo]

That's not the only possibility, see

Post 264850

(ChemicalSolution: "space efficient, easy 2-Br-propionic acid prep", Methods Discourse) &

Post 396684

(Aurelius: "Patent References  US patent 4319059", Chemistry Discourse).

[tmpvar]

I read somewhere that Nitro RC Fuel contains nitromethane...  What would using nitromethane instead of nitroethane change in the rxn? would it change the rxn or are they "interchangeable" (for lack of a better word)?

thanks for your time!

[Nick_J]

Nitromethane is present in model plane fuel and similar products, generally at around 20% concentration. It is mixed with castor oil (non-polar) and methanol (polar), which means extraction can be harder than you might at first think. It can be extracted by fractional distillation though.
Or, if you search a little harder, then in many places you can find PURE, 99+% NM at a reasonable price. But in some areas you cannot buy this lovelly product   .
Anyway, where was I... ah yes, I remember. NM cannot be substituted for NE here. As I understand it, using NM would lead to (in the case of using piperonal) 3,4-methylenedioxyphenylethylamine - MDA but without the methyl group on the carbon that's bonded to the -NH2. PIHKAL states that this compound is not active, at least not at 300mg.
I have an idea for you to think about/laugh at though...
CH3-NO2 + CH2O --> HO-CH2-CH2-NO2
IIRC this reaction happens quickly in slightly alkaline solution at around 50*C... the orgsyn database has a procedure if you want to have a look.
Would this not condense with piperonal just as NE does? Then if you could get rid of the -OH... (I'm not sure how to do that!) Or maybe the "MDA-ol" would be interesting as it is? I dunno.
It would be nice if this worked, making NE is a pain in the ass compared to buying a gallon of NM...