Sciencemadness Discussion Board
Not logged in [Login ]
Go To Bottom

Printable Version  
 Pages:  1    3
Author: Subject: Recommendations for synthesis of medicines and other medical organic molecules.
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 29-7-2020 at 02:31
Recommendations for synthesis of medicines and other medical organic molecules.


I am looking into putting my skills as a chemist to the test by making a small array of *US legal* chemicals. I always liked making chemicals that could have some sort of effect on the human body besides harm. Extremely easy chemical synthesis like nitrous oxide or chloroform are out of the picture as any monkey can make these with absolute ease.

Through digging on Wikipedia and other sites, I have found three chemicals I think are fairly possible for an amateur to make:


Chlorobutanol- Fairly easy to make and the only issue is usually recrystallization. It tends to form an oil instead of a crystal strucuture. I would make chloral hydrate but it's regulated and deals with elemental chlorine.


Isopropyl nitrite- Not really a medical chemical, but does have an effect as a potent vasolidator and possible mild euphoria. Fairly easy synthesis via sodium nitrite, isopropyl alcohol, and HCl and the reaction is very controllable if done properly. Big fire hazard as it is very volatile and flammable, but with proper safety equipment and keeping everything cold, this shouldn't be an issue.


Propofol- This would be a very difficult reaction for me. From what I have been able to scrap together, phenol is first sulfonated in hot concentrated sulfuric acid. This serves to add protecting groups. Isopropylation follows which is supposed to be an addition of isopropyl alcohol in HCl. Then the sulfonated product is desulfonated via hot dilute sulfuric acid. I wasn't able to find much on the synthesis that uses obtainable chemicals like phenol, H2SO4, HCl, and isopropyl alcohol and I think this is a synthesis I wouldn't be able to pull off.


Does anyone have some non illegal "drugs" that are feasibly synthesized in an amateur lab? I would need something that isn't piss easy to make like chloroform, but also something that isn't too hard. Multiple steps are okay. Nothing more toxic than 100mg/kg, no halides except for iodine, and preferably something that can be synthesized fairly safely.

Any chemical suggestions or tips to the right direction would be really helpful.
View user's profile View All Posts By User
B(a)P
National Hazard
****




Posts: 435
Registered: 29-9-2019
Member Is Offline

Mood: Confined

[*] posted on 29-7-2020 at 03:56


Nitroglycerin seems to fit your criteria - not sure about US legality though, also your 'fairly safely' criteria is a bit subjective.
Also these guys have some interesting ideas.
https://fourthievesvinegar.org/

[Edited on 29-7-2020 by B(a)P]
View user's profile View All Posts By User
Fery
National Hazard
****




Posts: 276
Registered: 27-8-2019
Location: Czechoslovakia
Member Is Offline


[*] posted on 29-7-2020 at 04:27


Advanced Practical Medicinal Chemistry
https://www.pdfdrive.com/advanced-practical-medicinal-chemis...

propofol synthesis (from phenol)
http://www.umich.edu/~chemh215/CHEM216/HonorsCup/HC%20250-IV...
you'll be able to do it, do not underestimate yourself

propofol synthesis (from 4-hydroxybenzoic acid - no need to sulfonate, there is COOH instead of SO3H), you can obtain the acid by hydrolysis of parabenes
Attachment: pramanik2014.pdf (412kB)
This file has been downloaded 65 times




If there is a heaven, it seems not to be materially based. Does chemistry exist there and if yes, how does it look like? Are there good souls well supplied with laboratory equipment, glass, chemicals and information?
View user's profile Visit user's homepage View All Posts By User
Metacelsus
International Hazard
*****




Posts: 2423
Registered: 26-12-2012
Location: Cambridge, MA
Member Is Offline

Mood: Double, double, toil and trouble

[*] posted on 29-7-2020 at 05:12


Benzocaine is also a good target. You can do toluene -> p-nitrotoluene -> p-nitrobenzoic acid -> p-aminobenzoic acid -> benzocaine



As below, so above.
View user's profile View All Posts By User
Dr.Bob
International Hazard
*****




Posts: 2200
Registered: 26-1-2011
Location: USA - NC
Member Is Offline

Mood: No Mood

[*] posted on 29-7-2020 at 06:54


I second benzocaine or lidocaine, it is a great experiment, and easy to tell if it worked. I taught this in a sophomore chem. course to 20 people a few decades ago, and most got it, but not all, so not a slam dunk. And the yield varied wildly, so a great test of your skills. Luminol is not a drug, but a great target and fun to show kids. Sulfa drugs are also doable targets, depending on what you have available.

For the really ambitious, Viagra and Cialis are possible to make, but not easy at all, but there are several improved newer routes, some using microwave for ceratin steps, some continuous flow steps, and some solid phase catalyts also. I think Stephen Ley published one of them. They are also easy to tell if they worked...



View user's profile View All Posts By User
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 29-7-2020 at 11:02


As far as the recommendation of nitroglycerine goes, I have made vasolidator nitrate esters before. I made erythritol tetranitrate and worked on the synthesis for a couple of months to attempt maximum yields using various nitrate salts. Trinitrophenol was a burn medication for a while and I have made some before as well but it was for energetic testing. The problem is that those were my past days of energetic synthesis and I have been using other organic synthesis to get away from energetic chemistry. Don't get me wrong it was super fun :P and I had actually managed to discover a synthesis of silver acetylide double salt synthesis to get high purity product with ease which many struggle with. Making high explosives in my state is legal but the problem is the unwanted attention you can get from it. The fact that I often have to go through an area that sometimes pulls you aside randomly for bomb sniffing dog checks also puts me at edge. I'd rather not have to explain myself to authorities. So while I am definitely experienced enough to make nitroglycerine and have all of the reagents on hand, I'd rather perform some other chemistry. Thank you for the recommendation and link to the site though!

I will definitely add benzocaine and lidocaine to my list of "drugs" I'll attempt to synthesize. I had looked at a synthesis of benzocaine before but for some reason didn't like something about it. I'll revisit the synthesis and I'll see if it is something I'll attempt. By the sounds of it, it is very doable, so thank you for those recommendations!

I have thought about luminol synthesis and since I will be ordering potassium hydrogen phthalate to make phthalic acid and phthalic anhydride for some pH indicator synthesis (thymolphthalein and the famous phenolphthalein), I may very well try it. I haven't put much effort into looking deeper into the synthesis but from one quick overview of a synthesis route I saw that you need hydrazine. Making hydrazine sulfate to make hydrazine in situ isn't really something I'd want to do. I was watching a video on hydrazine sulfate's synthesis and some pure hydrazine had crystallized out onto the cold beaker during the process. Pure hydrazine is a no go for me due to the whole potent neurotoxin and strong carcinoge thing. I'll look into alternative synthesis and it will be a potential addition to my list of organic molecules to synthesize. Thank you.

[Edited on 29-7-2020 by fdnjj6]
View user's profile View All Posts By User
Cou
International Hazard
*****




Posts: 840
Registered: 16-5-2013
Location: Dallas, Texas, USA
Member Is Offline

Mood: Mad Scientist

[*] posted on 29-7-2020 at 11:38


Nitrous oxide and 2-methylbutan-2-ol are legal recreational drugs. Though you need bromoethane for the grignard reaction.

[Edited on 7-29-2020 by Cou]




my youtube channel: https://www.youtube.com/channel/UC0qzaRyHxLUOExwagKStYHw
Buy fragrance compounds at www.jupiterfragrances.com (under construction)
View user's profile Visit user's homepage View All Posts By User
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 29-7-2020 at 11:56


Thank you for the reply!

Nitrous oxide is too easy to make. Just heat pure recrystallized ammonium nitrate and dry the gas that is evolved.

While looking through wikipedia I did find 2-methylbutan-2-ol an interesting candidate. I have the glassware needed for a grignard reaction but I'd have to make the bromoethane and dry diethyl ether first. Since grignards are also so unreliable, I don't know how well I could pull off the reaction.

Also a question that popped up is at what point, and how, would you separate the isomers for making benzocaine? So far, the separation of the isomers seems far from trivial. Benzocaine requires the para nitrated product. Meta is formed at a low amount, so ortho would be the main impurity. Someone had mentioned steam distillation to seperate o-nitrotoluene. If I pulled off a steam distillation, the para product should be left behind and could be recrystallized for higher purity. Is this feasible? The boiling points of the isomers are pretty close together so I question how well of a separation I would actually get.

I have a pretty good synthesis of benzoic acid that I would love to try and I could nitrate the benzoic acid. I don't have strong nitric acid though. I need to titrate the dilute nitric acid I have and see how strong it actually is. When I used to perform energetic nitrations I would opt for the nitrate salt method. Is it possible to use an excess of 93% sulfuric acid to pull away enough water to successfully perform the mono nitration? Better yet, does anyone know if a nitration bath prepared using a nitrate salt is viable for the mono nitration of either toluene or benzoic acid? Everything tells me it definitely would work just fine and some water could be included to make sure the acids aren't so concentrated that they begin to favor dinitrated products.

[Edited on 29-7-2020 by fdnjj6]
View user's profile View All Posts By User
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 29-7-2020 at 12:28


Could you separate the two isomers by adding it to chloroform? I don't know how soluble both would be in the chloroform but since the density of chloroform is 1.49 g/cm³ and the density of o-nitrotoluene is 1.1611g/cm^3. Theoretically, would you be able to add the two isomers to chloroform and agitate the isomers to have o-nitrotoluene rise to the top of the chloroform and skim it off? Then purify the p-nitrotoluene via recyrstallization.
View user's profile View All Posts By User
karlos³
International Hazard
*****




Posts: 919
Registered: 10-1-2011
Location: yes!
Member Is Offline

Mood: verrückt & wissenschaftlich

[*] posted on 29-7-2020 at 12:47


They usually separate that for methaqualone synthesis by separation because one is a solid and the other is a liquid.
View user's profile View All Posts By User
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 29-7-2020 at 12:53


Yea I saw that one is liquid and the other isn't but how would you separate them? I imagine that p-nitrotoluene is soluble in the ortho product. Threads that discussed the separation said it was difficult.
View user's profile View All Posts By User
Syn the Sizer
National Hazard
****




Posts: 418
Registered: 12-11-2019
Location: Canada
Member Is Offline


[*] posted on 29-7-2020 at 15:16


Quote: Originally posted by Cou  
Nitrous oxide and 2-methylbutan-2-ol are legal recreational drugs. Though you need bromoethane for the grignard reaction.

[Edited on 7-29-2020 by Cou]


I had no idea tert-amyl alcohol was a recreational product. I had always though the only alcohol we could consume without hurting ourselves severely was ethanol.
View user's profile View All Posts By User
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 29-7-2020 at 17:37


I believe it even has very similar effects as ethanol.
View user's profile View All Posts By User
Cou
International Hazard
*****




Posts: 840
Registered: 16-5-2013
Location: Dallas, Texas, USA
Member Is Offline

Mood: Mad Scientist

[*] posted on 29-7-2020 at 18:29


It's even healthier than ethanol because it doesn't get oxidized to toxic aldehydes or ketones.



my youtube channel: https://www.youtube.com/channel/UC0qzaRyHxLUOExwagKStYHw
Buy fragrance compounds at www.jupiterfragrances.com (under construction)
View user's profile Visit user's homepage View All Posts By User
karlos³
International Hazard
*****




Posts: 919
Registered: 10-1-2011
Location: yes!
Member Is Offline

Mood: verrückt & wissenschaftlich

[*] posted on 29-7-2020 at 19:19


Thalidomide was pretty easy to make too, by the way.
View user's profile View All Posts By User
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 29-7-2020 at 20:12


Okay so I have the synthesis from toluene to benzocaine figured out. However, it'd be great if someone has some actual lab notes and preparation of this method so I can cross reference the steps and make sure everything will go smoothly.

I'll start by nitrating toluene to mononitrotoluene. I wanted to use benzoic acid at first but the nitro groups don't end up in the position I need them to be at. The isomers will be separated via chilling the crude product. Then the product is recrystallized.

The p-nitrotoluene is then oxidized to p-nitrobenzoic acid using sulfuric acid and KCr2O7. I have found a video that also shows this reaction and they seemingly had success, however, a different preparation I found heated the nitrotoluene with glacial acetic acid before the KCr2O7 step so I am slightly confused. The acetic acid seemed to be a major part of the synthesis yet the video says otherwise. Assuming the video was right, I move on to the next step.

The p-nitrobenoic acid has its nitro group reduced to an amine group via tin/HCl method. I found a preparation of this step online so hopefully it will work.

The final reaction uses the p-aminobenzoic acid and I carry out a Fischer esterification using ethanol and sulfuric acid.

Assuming all of these steps go right, I should get my product. Does this all seem right? I had huge trouble finding preparations documented anywhere for most of these steps so the total synthesis is basically a Frankenstein of other site's methods.
View user's profile View All Posts By User
stephill92
Harmless
*




Posts: 21
Registered: 19-3-2019
Member Is Offline


[*] posted on 29-7-2020 at 20:31


Chemplayer has a series on making benzocaine on bitchute, however he did a fischer esterification first and then reduced the nitro group using sodium dithionite solution. Here's the video: https://www.bitchute.com/video/ZWJZPemwJdm5/
View user's profile View All Posts By User
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 29-7-2020 at 21:00


Awesome! I used some of his videos for reference but thought he gave up and failed since I couldn't find a video on p-aminobenzoic acid.

So seeing how he was actually successful in the p-aminobenzoic acid synthesis, it looks like I can use that video for help.

The only thing is that I do want to try the reduction of the nitro group into an amine using the traditional methods of HCl and a metal. I have only found one procedure that uses tin as the metal.

The part that is a little foggy is when they add ammonia to it. It makes sense since it gets rid of the tin ions but what follows is just written weirdly. It says:
"Add concentrated ammonia solution until the solution is just alkaline to litmus and digest the suspension of precipitated hydrated tin oxide on a steam bath for 20 min. Add 10g of filter aid... (they basically vacuum filter and wash the remaining product out of the beaker using hot water)... Concentrate the combined filtrate and washings until the volume has reduced to 157-200 ml:filter off any solid which separates.

Acidify the liquid to litmus (what is that supposed to mean? I'm pretty sure they just want the solution to be mildly acidic) with glacial acetic acid (can other acids be used too? Although I think HCl is strong enough to form salts with the benzocaine, not sure about this step) and evaporate on a water bath until crystals commence to separate; cool in ice; filter the crystals and dry in the steam oven."

The yield is 77%. It just sounds a bit off, I've been researching this all day already and my head hurts, but if I'm undersanding it right, you basically reflux the p-nitrobenzoic acid with HCl and powdered tin, then to precipitate the tin ions you add ammonia, the p-aminobenzoiv acid is deprotonated by the ammonia and forms a salt or complex that is destroyed after acidifying the solution with acetic acid. Then boiling or evaporating the water will leave me with my product which I can perform a fischer esterification on to finally get benzocaine.
View user's profile View All Posts By User
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 29-7-2020 at 21:18


Woah I was watching chemplayer's reduction experiment and he said that they had tried the tin and HCl method on nitrotoluene in a separate video. Anyone have a link? I can't find it.
View user's profile View All Posts By User
RogueRose
International Hazard
*****




Posts: 1518
Registered: 16-6-2014
Member Is Offline


[*] posted on 29-7-2020 at 22:28


This thread is pretty close to drug production isn't it (against forum rules)? I find it suspicious the 3 things picked are extremely strong sedatives with high potentials for abuse and misuse.
View user's profile View All Posts By User
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 29-7-2020 at 23:15


I didn't mean for it to be. Propofol would require some form of pain reducing agent I believe and it's rather hard to actually use. I am honestly just looking for organic synthesis with purpose. I have been planning phentolphthalein and thymolphthalein synthesis and the reason I don't mention it here is because the synthesis is well documented and easy to reproduce for me. Multi step organic synthesis of benzocaine aren't. Ispopropyl nitrite isn't a good "popper" and that's why it's legal and the butyl version is illegal (I believe). Chlorobutanol is also mainly a hypnotic sedative and isn't good for producing a euphoric effect which is probably why it hasn't been banned yet. It's also highly toxic to the liver. I honestly just want to get away from the energetic chemistry past I have and move on to more applicable and safer synthesis.

It's been a dream of mine to successfully pull off a multistep organic synthesis that ends with a product that is commonly used and has a larger structure than just some simple alkene. I was going to prepare acetaminophen but guess who doesn't have the balls to make acetic anhydride? This guy. Ketene is too much for me as I am still a flowering chemist. I'll never make ketene in fact. It's too much. I love the synthesis of sodium azide and it would use all of the new advanced glassware I have coming in but it is faaaaarrrr too toxic. I have a lot of experience in safety practices and have taught myself a lot of theory, however, there is a lot I still don't know. Explosives gave me a good direction as most were fairly easy to make and the results was always fun. Like I said I want to get away from this type of chemistry. It's not illegal where I live, it's just lots of potential trouble and dangerous.

Just researching the whole synthesis for benzocaine from toluene I have learned so much. I learned various methods to reduce nitro groups to amine groups (I only knew Pd/C method so far), oxidizing the methyl group of toluene to a carboxylic acid, etc. Just loads I've learned. Now, theoretical does me nothing unless I can actually do it practically. Everyone who reads one article on clandestine manufacture and knows the reactions needed and chemicals needed can say they can make it, but in reality it's not that easy.

I am also just seriously trying to test my chemistry skills. I have performed mainly simple reactions but I have an upgrade in glassware coming and lots of time due to the virus so I thought now is the best time to give it a shot.

I assume that the three things I picked were because they were easily made and since they do have potential for some abuse they are more popular. I found out about chlorobutanol through some friends who watch NileRed and found it awesome. Isopropyl due to sodium azide. Propofol by looking at potential chemicals on Wikipedia. I liked the fact that chemicals can have a biological effect too. Just fascinating to me.

If I wanted to make meth or some legal drugs, I wouldn't result to this site. There are plenty of other sites and a lot of sites literally have synthesis for various amphetamines, GHB, LSD, ketamine, MDMA, etc. Many also have drugs that are legal and easy to make but I don't care for the euphoric effects of whippits and stuff like that. I want the chemistry.

[Edited on 30-7-2020 by fdnjj6]
View user's profile View All Posts By User
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 29-7-2020 at 23:20


Also I hope that the fact that I right away asked about benzocaine's synthesis, which I knew had 0 narcotic effects, is a sign of me not giving a shit about the actual effects. I was mainly choosing these chemicals due to their relative ease of synthesis. I still don't believe I could pull off the propofol synthesis but I have my notebook filled with notes and plans for the benzocaine synthesis because it is exactly what I was looking for. An awesome multistep synthesis. I am sourcing my toluene from carb cleaner so how cool is it to know you made a modern weak anesthetic from freaking carb cleaner?

To me that is just amazing and will hopefully be a way to see how good of a chemist I am. I suspect I will have lots of trouble with the whole synthesis but I think thinking things through, planning, and lots of research and help from sites like these will help me achieve my goal.
View user's profile View All Posts By User
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 30-7-2020 at 01:05


I'd also like to thank Fery, I just read the book that he sent and it contains very good information. The initial synthesis I was going to use would have created issue for isolating the p-aminobenzoic acid due to only neutral conditions being where it is insoluble. I will have to follow a different route which the book mentions. I'll also have a look at the other chemicals that could be made. Thank you.

[Edited on 30-7-2020 by fdnjj6]
View user's profile View All Posts By User
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 30-7-2020 at 01:15


Forget what I said. The HCl/Zn reduction is part of the synthesis mentioned so I was wrong.

The benzocaine structure is still wrong though as it has a nitro group instead of the amine group.

Is reduction via CaCl2, 95% ethanol, and Zn powder something that is actually easily reproduced?

Step-III. Reduction of Ethyl p-Nitrobenzoate.
(1) Transfer 1 g of calcium chloride in 12 ml of water placed in a 100 ml beaker ; and mix
this solution with 55 ml of 95% (v/v) ethanol.
(2) Pour the resulting solution into a 250 ml round bottom flask that contains 2.5 g (0.013
mol) of ethyl p-nitrobenzoate (Step-II), add to it 25 g of Zn-dust, and attach to it a
reflux condenser.
(3) Reflux the reaction mixture for 2 hours gently and at a stretch and then cool to room
temperature.
(4) Separate the unreacted Zn-dust from the aqueous ethanolic solution in Büchner funnel under suction, and wash the filtered solid with two 25 ml portions of solvent
ether.
(5) Extract the filtrate with 150 ml of water previously saturated with NaCl. Wash the
aqueous layer twice with 25 ml portions of solvent ether. Combine all the ethereal
layers together (including one obtained in (4) above ; and wash it with two successive
portions each of 40 ml of water.
(6) Dry the resulting ethereal solution over anhydrous Mg SO4, filter, and subsequently
distil the ether on a steam bath to a final volume of 10 to 15 ml. Transfer the ethereal
residue to an Erlenmeyer flask and add to it 20 ml of pentane to precipitate the
desired product benzocaine.
The yield of the crude benzocaine is 1.58 g having mp 88-89.5°C.

It seems like it worked for them but I have never heard of such a reduction before.

[Edited on 30-7-2020 by fdnjj6]
View user's profile View All Posts By User
fdnjj6
Banned by request
***




Posts: 114
Registered: 20-2-2019
Member Is Offline

Mood: Pissed

[*] posted on 30-7-2020 at 02:40


Shit, don't forget what I said. The reaction calls for dilute acetic acid but it's never added! Wtf kind of a book is this?? Multiple things already wrong and I only looked at one reaction so far.
View user's profile View All Posts By User
 Pages:  1    3

  Go To Top