hi guys a birch reduction of crystallized alkaloid of harmala is being considered to be performed

predictions on the product of such a reaction would be appreciated. different degrees of reduction can be predicted stoichiometrically so you know if something really cool could be developed after say 3 or 4 reductions that would be cool to know.

also let's discuss something that has always been wondered
uh in the textbook it is said that the reduction can be performed in a solution of anhydrous ethanol of concentration 10 percent ammonia whereas it is commonly stated that pure cryogenic ammonia is to be used

the tell-tale indigo could clear things up but peeling apart a battery at the moment especially without harmala alkaloid prepared doesn't seem very appealing

That sounds quite ambitious. Why wouldn't you use magnesium or zinc in acetic acid? It's easier - but if you want to use lithium it's likely to be capable of reducing harmine as well. I guess stoichiometric control is what you'd have to rely on for preventing unwanted reduction of the pyrrole and/or benzene rings.

Alcohol is added to Birch reductions as a source of protons; I don't know the solubility of harm(al)ine in liquid ammonia [does anyone?] but I would think that ethanol would be the better solvent here.

This is a procedure that presents significant fire, explosion, and toxicity risks. How will you be ensuring your safety? Please answer this carefully or you will find that your thread gets deleted.

For starters, dismantling the lithium battery is clearly best done only immediately prior to the reduction itself. Prior to that you need to prepare your anhydrous ethanol - and how will you ensure that it is in fact anhydrous, and that it stays anhydrous? And before you do any of that you need to prepare and isolate your harmala alkaloids. So don't put the cart before the horse.

First of all, what you are describing here is not a birch reduction. A birch reduction is the reaction that transforms an arene into a cyclohexadiene. (only harmine, like DFZ mentioned, would participate here in the first step of the reaction) There is a common misconception among the drug chemistry crowd that anything with lithium and ammonia is called a birch reduction, because that's what they read in some shake and bake methamphetamine tek on the internet, and that's the only reason they know the name birch reduction, but the tek is also wrong. In the birch reduction, you need ammonia or another cryogenic liquid amine (ethylamine, methylamine) to generate the solvated electrons necessary to initate the birch reduction, which has a unique mechanism specific to the reaction. But metals like lithium and sodium are still perfectly good reducing agents on their own in the right conditions. And actually, you don't want to be using lithium here..

I've actually carried out these reductions on harmalas in the past, if you are just after THH, it's not the way to go. Zinc is a metal too, my preferred route is using NaBH4. Although if you are simply curious, that's fine too and that's why I initially carried out my experiments. Although as a bare minimum, you have to be able to do the basic prediction of products, if you don't know the mechanism or what will happen and what you are making, why would you carry out the experiment at all? You won't be learning anything that way. Get a piece of paper, or download chemdraw, and start working out the mechanism and the reduction products, don't worry about making mistakes, I'd be happy to help you out there. I'd enjoy going into detail here but It's not really helpful simply spoonfeed all the answers here and waste my time if your not really interested.

Mindlusion, not trying to provoke you:

Have you posted a simple THH tek here, seems you have the expertise?

If so, please provide the link, many members seem to be focused on this atm?

If you haven’t, why not do us all a favor?

No problem Cheelin

I demonstrated my nabh4 method back in 2016 as an alternative to zinc/acetic acid
https://www.dmt-nexus.me...m=752319&#post752319

A simple search of "NaBH4 THH" or "Mindlusion THH" could have found it for you.

Its very straightforward, you don't need to overcomplicate it with a step by step 'tek'

Like I said, thanks.



Vixintrex, I apologize to you for asking a somewhat related, off-topic question on your thread.

Let's try to be nice, people.

hye people thanks. I probably don't have to do this. I was almost more excited about seeing solvated electrons than anything else but tetrahydroharmine looks really cool too. Yeah, doing this would almost be an exercise in producing anhydrous ethanol and would be really dangerous. I understand that any anhydrous alcohol above 95 percent sucks water from the air and tries to go back to 95 percent but I was

I was that guy you know that wanted to do that thing that nobody did but actually that guy already did it too. he did it and he did it for tetrahydroharmine which was super cool and maybe later I can do it too after I learn to appreciate how cool that stuff is but at the moment I think I got my answer you know like I understand that the enzymes responsible for really cool stuff like to at a last step synthesize harmine from tryptamines and I was asking if we could ask them kindly to undo that

after thinking about it on my own I had to admit that a birch is good for what it is good for which is making cycloalkanes out of aromatics and I'm delighted in seeing that the product of such a process would be cool but my silly hypothesis that it could cleave that bond in particular I have to admit was silly and I probably won't be attempting this experiment. but I'm sort of glad I brought it up as I did receive my answer:

tetrahydroharmine

word to that guy: mindlusion

and uh so I hate to press this issue further but if tetrahydroharmine was subjected to a birch we would totally see the left half of the molecule get totally hydrogenated next and next again right?

I'm possibly bad at chemistry so when I think of 'adding a hydrogen to a molecular structure' I could occasionally imagine it could sever an existing molecular bond, especially between two atoms that are different. I don't necessarily understand what bond strength relies on. Is it atomic weight? I know that pi bonds are like twice as strong in relation to external forces like heat, but when subjected to chemical attac they show their true nature as angular differences from a pure relation. daimonds are very strong. I don't know what that has to do with anything. I guess nittrogen is heavier than carbon, so is a carbon nitrogen bond stronger than a carbon-carbon bond?

Bond energies are something you can look up. With organic chemistry, the degree of conjugation of double bonds also has to be taken into account, along with the electron donating or withdrawing effects of substituent groups. The atomic mass of the participating atoms is not strictly relevant (except, perhaps, in the special case of hydrogen versus deuterium). That said, generally it's still easier to reduce (add hydrogen to) a carbon-nitrogen double bond than to a carbon-carbon double bond, in part because of the polarity of the former.

Press away, this is cool stuff, and my favorite way to learn, teach, or review chemistry is when it is associated with molecules close to my heart. I also agree, seeing the blue color of the solvated electron metal-ammonia complex is enough reason to be interested in this reaction.

There is quite a lot going on here. And quite a large number of possible products, especially if you are putting harmine and harmaline in there, not just THH.

But lets keep things simple for now and talk about what might happen with THH in there.

You are right, you would expect to see the left half (benzene ring) get hydrogenated. But you would not expect to see it become totally hydrogenated, you would expect a partially hydrogenated product (dihydro), a diene as typically expected from a birch reduction. However, this is going to be largely driven by the reaction conditions, whether Na or Li is used, what alcohol proton source you use, the amine used and any cosolvents, the temperature, etc. The main variable that will affect the regioselectivity and reduction product, is actually how fast the protonation step occurs. If you could get dianion formation, you might expect to see the 2,3 bond reduced to form an indoline. You would also expect further reduction products depending on the regioselectivity of the birch reduction, if the diene ended up conjugated with the pyrrole, further reduction to the tetrahydro- product could result, or the associated decomposition products. But because in THH (1) the indole possesses a 6-methoxy group, this is actually going to serve to direct the regioselectivity so we end up with the dihydro product (2), which is going to be stable enough to resist further reduction under these conditions, so I am pretty certain that in the right conditions, you could see this as your primary product. However, since this product is actually now an enol methyl ether, under Lewis acidic conditions you might it expect to hydrolyze down to the ketone product (2a), but under purely the reduction conditions , you probably would not expect this to happen.

As for your questions about bond strength, we are indeed breaking bonds here, but only the pi-bond double bonds. Practically all of the chemistry happening in the birch reduction is happening through and across pi bonds, it all starts when an electron is added into the LUMO of the molecule's pi-system. You aren't going to have C-N cleavage here, although under sufficiently harsh conditions, hydrogenolysis is possible, but not without some kind of catalyst, the beauty of the birch reduction is that it is partial, so it can be employed when you don't want a complete hydrogenation. So the birch is not what you want to use for making cycloalkanes, (it makes cyclohexadienes) for that you would be better off with catalytic hydrogenation, using Pd or Pt metal catalysts. Infact you could see a birch reduction, to get a cyclohexadiene, to break the aromaticity, and then a catalytic hydrogenation, to reduce it down to the alkane. The problem with reductions breaking aromaticity, especially in something like harmaline, or harmine, is that these molecules will re-aromatize if they get the chance, through hydride shifts, or even allowing something like a transfer hydrogenation if there is a catalyst involved.

Your understanding here in your last paragraph is flawed, but you are on the right track at least thinking about it. What makes a bond and what makes it strong and what makes it possible to break. I recommend looking up a first year organic chemistry lecture, focus on things like electronegativity, periodic trends, and molecular orbital theory and hybrid orbital theory. This is what its all about. pi-bonds aren't twice as strong, they are weaker, that is part of why this chemistry is happening, DOUBLE bonds are what you are thinking of (sigma + pi bonds together), double bonds are not twice as strong (because pi bond is not equal to sigma bond) but are almost twice as strong, that must be your confusion. pi-bonds are naturally weaker because their overlap isn't as good. Pi bonds need to rely on parallel orbitals overlapping from two close together atoms, where sigma bonds can have direct overlap. It is not weight, but bond length, that the strength is proportional to, and this makes sense when you think about overlap. Orbital overlap, and electronegativity, are the key components of bond strength. It is very much geometric when it comes to molecules and bonding, but you need to understand the behavior of electrons (fermi mechanics) to see what drives bond formation and bond breaking.

Wow, that post was very informative and really awesome. I took organic chemistry in school and it was really exciting. It's been a few years now and it's not like I've forgotten the information, but rather the big picture in regards to how and when a reaction can occur. I think that the most important thing in regards to organic chemistry is that carbon is relatively inert compared to most molecules. I guess this is due to their position in the periodic table being so far away from either sides and also being a non-metal. I think there's some important aspect to that I'm overlooking that sums it up nicely. The funniest thing about it too is that the more harder I think about organic chemistry the more I forget the things I know and how they work and I sort of have to forget about the concept that I'm contemplating in order to remember that I already know the answer to the question I'm looking for. Right now is one of those times.

Carbon doesn't like to form ions very often. I think I remember reading about superacids once where the very definition of their development was that it was capable of dissolving a paraffin candle and those are double bonds so I would even imagine those to be more susceptable to attack than hydrocarbons. Or not, I'm not sure. In the end, the answer is enzymes. I still have my book. I've been really looking forward to breaking it open again one of these days. The last few years of my life have been a lot less studious than those afore. I used to really dig studying and learning and although I waste hours on wikipedia I rarely break open the books but I think hereforward I'm going be diligent in brushing up on the things I've learned. Thank you. Cool pic too. I'll treasure that.