Chemistry Discussion Thread

[MrEDuck]

I can't comment on getting precursors as I haven't done that in a long time.
I haven't had a copy in a long time, could you post it?
I've only ever done a bisulfite wash.
A short column is very nice if you're distilling safrole.

 

[BusyBee123]

Can do, here you go!

Sit down with some coffee and read through #4 and #5 on her top ten list. I'm going to be doing some more literature searching this afternoon over lunch on these two methods, but I want to get some more opinions. It's been 14 years since TS2 was published, I can't imagine these would have gone unnoticed (though I suppose most people don't have mercuric acetate at their fingertips....ah academia!)

 

[BusyBee123]

Well, after some more research, I threw out safrole as a precursor. It sucks, but it's well-regulated and I don't want to be breaking the law with my purchases

I am however very intrigued by the safrole total synthesis from salicylaldehyde. Most of this route is peroxide chemistry but near the bromination of 1,3-benzodioxole to 1,2-methylenedioxy-4-bromobenzene (see Strike's TSII, page 222-230).

This is really the only step I had nightmares about (the grignard addition of the carbon side chain to the benzyl frame isn't bad, dryness is no stranger to me) is this bromination, but in the best way possible. Two high-yield bromination routes are given"

Method #2: To make dibromodioxane one stirs 500g dioxane in a flask which is in an ice bath, all of which is in the hood. 990g liquid Br2 is rapidly added, causing the solution to get hot. The solution is dumped into a bucket containing 2L of ice water, causing the immediate formation of a large mass of orange dibromodioxane crystals which are separated by vacuum filtration and dried. In an ice bath a flask containing 100g 1,3-benzodioxole or catechol or guaiacol and 200m: ether is stirred and then 200g dibromodioxane is slowly added so that the heat and reaction won't get out of control. After stirring for 1 hour the solution is poured into some water and the ether layer is separated. The aqueous layer is extracted once with some more ether and the two ether fractions combined, dried through sodium sulfate, and distilled to give bromo-benzodioxole (90%).

This method employs the bromine delivering group of either a brominated dioxane or succinamide, which I know would help avoid re-brominations (though I would imagine keeping the solution cool avoids this?) but I'm trying to figure out why any poor fool would do it when they had just read the first synthesis in that section:

Method #1:143g 1,3 benzodioxole in 600mL chloroform is stirred in a flask and Br2 from a little tank is slowly bubbled through the solution over a period of 4 hours at room temperature. Ideally one wants to introduce about 190g of bromine into the flask so the chemist may wish to stop the bubbling and check the weight gain of the flask periodically. after 4 hours the solution is vacuum distilled from the flask. The first thing to come over is the chloroform, then a small amount of higher boiling, unreacted benzodioxole, and at about 30-40C higher should come the mother lode of yellowish bromobenzodioxole oil (yield=91%). Using acetic acid and liquid bromine, yields of up to 90% are described.

Unless I'm missing something, why would a chemist want to use a recyclable bromine donor, when yields are comparable and you save time not using one? What's not being said here?

 

[MrEDuck]

Allyl catechol thermally rearranges to make 3,4 dihydroxyallylbenzene. Allyl bromide and catechol are about as basic of building blocks as you can get.

 

[BusyBee123]

Hence the Grignard addition to avoid the rearrangement. But what about the bromination? What's the difference?

 

[MrEDuck]

The thermal rearrangement is easier than brominating catechol and then hitting it with a gringard. The difference is one is direct and doesn't require the use of a tempermental organometallic.

 

[BusyBee123]

Had to think about what you were saying for a while before I realized...I'm thinking that deprotonating the allylcatechol with a strong ionic base and then bridging the oxygens with DCM under anhydrous conditions would be swell. If i had my main computer I'd run some DFT calculations on the structure, but that'll be a few weeks yet.

 

[2cimdma]

I have never been ripped off when ordering from China. But of course it does happen a lot. It comes down to doing your due diligence and investigate the company as much as possible. Use Whois, google, and whatever else you can gather info from. Look to see if the company your buying from is going to be in any trade shows such as CPhI, etc. Do a reverse phone search and reverse address search on them. When I was trying to find a company to synthesize Bromadol HCl for me a couple years ago I was having hell of a time. So I ended up looking up translators over there who offer translation service for business meetings and such. I contacted a woman and she agreed to call companies/lab's there in China. She ended up finding a lab to custom make it for us within 3 days(I had been working months to find such a lab). All she charged me was $100 which I sent via paypal. When it comes to customs forms most companies will write what you tell them to write and they will do it for free. If you use a B2B site like Alibaba or lookchem, etc. you can do the instant messaging and talk to the supplier and get answers quickly. Just tell them what your looking for and ask if they will write something different on the form.

 

[MrEDuck]

Had to think about what you were saying for a while before I realized...I'm thinking that deprotonating the allylcatechol with a strong ionic base and then bridging the oxygens with DCM under anhydrous conditions would be swell. If i had my main computer I'd run some DFT calculations on the structure, but that'll be a few weeks yet.

DFT got too math intensive for me, damned neat stuff though.
DCM would be my last choice for a methylene source because Cl is a crappy leaving group. A phase transfer catalyst is a very good idea. There's some stuff in the rhodium archive.

 

[BusyBee123]

DFT got too math intensive for me, damned neat stuff though.

If you grab this (can't speak for the quality of the torrent) you can do the DFT calculations for molecules this size on an average laptop in a few hours. It spits out a really pretty 3D graph for your HOMO/LUMO and you don't have to touch an integral table.

China still sketches me out (that damn rare metal monopoly they have leaves a bad taste in my mouth), at least for something as explicit as sass oil/brown camphor shipped in bulk to a U.S. address. But would large quantities of parsley or cinnamon oils be cheaper than in the U.S. as well?

 

[budbro18]

Has anyone asked about a Ketamine synth? Ive looked them up and they seem fairly easy and straight forward i just cant find a working synth that people stand behind.

Like everything on the internet people denounce it and others say it works. let me know if youd be interested in bringing this up for a topic of discussion.

PM me if necessary

 

[Azide Intermediate]

Hi. New. Just some semi layman comments on ergot derivatives of fame. Is POCl3 that hard to source? Only going from Shulgins most straight forward synth in Thkl. Assuming you have ET. Per his words Pocl3 and dimethylamine is clean , fast and low side reactions. The peptide couplers seem to be dated back to the azide and TriSulpr. Not to say the reaction isnt workable. Just you need so little. ET no, but 2 magic ingredients and hours instead of days in kenny roasters red glare, if pride matters column chromo add tatar sauce and and recrystalize. It potent. Makes the roundabout cultivation ideas in realm of possibility. Get an internship at a chem minded employer and pipet what you need of the 2 other reagents.

Again all due respect to the in the know on modern peptide chem.

 

[Azide Intermediate]

DFT got too math intensive for me, damned neat stuff though.
DCM would be my last choice for a methylene source because Cl is a crappy leaving group. A phase transfer catalyst is a very good idea. There's some stuff in the rhodium archive.

I have a pressing question on DCM. I am not a layman but could you explain the Cl as a crappy leaving group. Very reactive but in using DCM in a peroxy acid route to the glycol and ketone. What side products or nasties are we talking. Besides the straight iso oxone red amination approach similar I guess. So iso into peroxy acetic and workuo using DCM solvent... ? I appreciate your feedback.

 

[Azide Intermediate]

What did these clowns cut my Molly with that makes it taste and smell like saw dust??

I wouldn't have even bought it if I didn't already tell my friend I'd go in half with him. I took one look at it and knew it was stomped on hard...

Molly i assume powder. Who the hell knows how they smuggles that in or in what. Dissolved in what. Hay and cut grass are and damned i cannot recall but ,Phosgene ??i know has that smell (ppb prob) So cleanup? Or it was packed with Chinese newspapers and apple cores. White crystals? Go on DanceSafe and see the cut these evil bastards use on a good day. Clean up ,thats time and money. Pills. Maybe god damed wood pulp as a binder since tab presses are rare. Hand mold like dumpling

 

[MrEDuck]

Hi. New. Just some semi layman comments on ergot derivatives of fame. Is POCl3 that hard to source? Only going from Shulgins most straight forward synth in Thkl. Assuming you have ET. Per his words Pocl3 and dimethylamine is clean , fast and low side reactions. The peptide couplers seem to be dated back to the azide and TriSulpr. Not to say the reaction isnt workable. Just you need so little. ET no, but 2 magic ingredients and hours instead of days in kenny roasters red glare, if pride matters column chromo add tatar sauce and and recrystalize. It potent. Makes the roundabout cultivation ideas in realm of possibility. Get an internship at a chem minded employer and pipet what you need of the 2 other reagents.

Again all due respect to the in the know on modern peptide chem.

POCl3 is some fairly nasty stuff that I will use but would prefer not to work with. Peptide couplers are things like PyBOP that are used extensively in making peptide bonds for synthetic proteins and such. Look up the Merrifield Synthesis to see where it began. Here's some stuff from Hardison http://bitnest.ca/Rhodium/chemistry/lsd.pybop.hardison.html

I have a pressing question on DCM. I am not a layman but could you explain the Cl as a crappy leaving group. Very reactive but in using DCM in a peroxy acid route to the glycol and ketone. What side products or nasties are we talking. Besides the straight iso oxone red amination approach similar I guess. So iso into peroxy acetic and workuo using DCM solvent... ? I appreciate your feedback.

I'm assuming this is related to the synthesis of safrole from allylcatechol? Making the MD ring from the diphenol is an S[SUB]N[/SUB]2 reaction, halides become better leaving groups as you go down the periodic table. DCM is a reagent as well as a solvent here. You need to make the phenols into better nucleophiles by deprotonating them and you need a PTC to let the phenoxide anion get to the DCM.

 

[Azide Intermediate]

From Québec, Canada ..probably youll be able to coopérate with me in learning and legal statuses advantages I got within 2-c family non forbid in my province and so for pseudoe, e, etafedrine, ethylephrine ect.. and spot easy cooks! Ive managed to synthesize some good stuff wtih allegra-d that is fexofenadine+120 mg pseudoe that Ive growed into a solution with H2o and filtered knowing that fexo isnt water dissolvable just there the pure pseudo after a good heet quench was so cute I would cry then Im tryin with a lithium strip and NaOH attacks..that seem right with a bronze allure to my lithium and all reactions done Ive tried filtering , acétone cleaning and there im stuck at the Hcl gizmo thing.....I use hcl 20% with Salt (Big salt NaCl only) to create something like ammonia I guess do I have to solubilze my e in water in first case and than with a gas gizmo introduce this in the solution? correct me I you like anybody Its for a cooperation Ive got nice hints to give ! Could you give me one here
JP!!

Hcl and salt. Non iodized. Is your gas generator. Should convert your base into something for snort or shoot. Is this this quick brew method? You playing with anhydrous ammonia? If i got the processes mixed forgive. You got to tack an ammonia on there somehow you are right.

 

[Azide Intermediate]

POCl3 is some fairly nasty stuff that I will use but would prefer not to work with. Peptide couplers are things like PyBOP that are used extensively in making peptide bonds for synthetic proteins and such. Look up the Merrifield Synthesis to see where it began. Here's some stuff from Hardison http://bitnest.ca/Rhodium/chemistry/lsd.pybop.hardison.html


I'm assuming this is related to the synthesis of safrole from allylcatechol? Making the MD ring from the diphenol is an S[SUB]N[/SUB]2 reaction, halides become better leaving groups as you go down the periodic table. DCM is a reagent as well as a solvent here. You need to make the phenols into better nucleophiles by deprotonating them and you need a PTC to let the phenoxide anion get to the DCM.

First my apologies. Nice thread. Yes I was just reading back a few pages and my comment does not dovetail with your thermal rearrange
. As you can decipher from my scratch, this pertained to iso as an option. While I am very glad you reviewed Dr Drool, and while it gave me a framework, times change. What I would really love is opinion on use of Oxone. Strong pool balancer but a peracid used in commercial chem in a pinch. The writeup is sloppy but seemingly sound. Plug into al/hg with insitu me.hcl and your there.

 

[Azide Intermediate]

POCl3 is some fairly nasty stuff that I will use but would prefer not to work with. Peptide couplers are things like PyBOP that are used extensively in making peptide bonds for synthetic proteins and such. Look up the Merrifield Synthesis to see where it began. Here's some stuff from Hardison http://bitnest.ca/Rhodium/chemistry/lsd.pybop.hardison.html

Man I got into that Ref using subs for the diethylamine using coupling reagents. I bumped into peptide chem in some LSA to LSD ref but no peer review. Its some heavy chemistry no doubt for study purposes. What would the human bioassay do with it? Its looks like lsd and binds magically by conformation. But does it have the sparkle? Yes thats a high end example. But being in non acedemia or its resources. Id strap on the gloves and hit the fume hood ala pocl3. Guess its the materials on hand and scarcity of ET. Anyway you know your shat. Cool to converse. Amazing that kicking in the door on such a fragile molecule worked or works.

 

[MrEDuck]

Nichols first used it to synthesize a lot of LSD analogs to try to determine the active configuration of the LSD molecule when bound to the receptor. The question wasn't if the method works or not, but if it could be used at scale. Based on what Freeblood got busted with I'd say it works quite well at scale.
LSD is LSD regardless of the synthetic pathway. If what Bear believed is true then the state of mind of the chemist during synthesis matters far more than the synthetic route employed.
We're discussing different things the mention of dihalomethane was for making the MD bridge to make safrole not to do some oxidation. Times may change but the Wacker oxidation is a simple reaction that uses easily obtained chemicals. Yes you can do it with peracid but it's a method I'm not experienced with.

 

[eastcoastmo]

Hey Mr Duck, sorry for bringing up an old thread but i was wondering how i woulf go about extracting safrole oil out of camphor laurel as its a ferocious weed here in oz that contains high contents of safrole. And how much safrole oil would i need as a precursor to make say 300g of molly? Im in no way going to try and make molly but have a mate that is well equipped and knowledgeable on how to do it correctly...

Great thread by the way mate, ive only studied enviro chem and base organic chem at uni so only have a base knowledge of it but this thread is unreal for info! Cheers for starting it hey