Making Vanillin Oxime (Capsaicin precursor)

[@turelish3408]

I know it's completely normal for chemistry, but turning vanillin, the nice vanilla flavour we love, to capsaicin, the devil of the chemistry world, is something quite fascinating. I can't wait for the synthesis of vanillylamine and then it would be awesome if you could turn that into capsaicin :)

[@elephystry]

I would rather we go into the reverse.

[@spiderdude2099]

TU Relish you should watch his series of videos where he converts vinyl glove plasticizers into grape flavoring. Chemistry is cool.

[@chemistryofquestionablequa6252]

Ethyl perchlorate is one of the real devils of the chemistry world. There are much worse things than capsaicin.

[@GarryDumblowski]

Hey, he finally published the vanillyl amine procedure! The whole procedure was completely redone from scratch and meshed into a single video as the total synthesis of capsaicin, but I mean, I'd argue it counts.

[@haharmageddontv6581]

i mean vanilla is called a spice

[@glenthemann]

Nile, the explanations are the best part! I mean, I love seeing the reactions take place and lovely precipitations, but knowing whats going on is the best. Keep it up bud :)

[@batmanh142]

Don't appologize for your explanations on mechanisms, it's important to know what your doing and why! :)

[@hairyasstruman2257]

He explains those reaction mechanisms better than my organic chem professor

[@Donald_Trump_2024]

@@hairyasstruman2257 what grade are you

[@Shouttz]

What the heck, I'm not even really into chemistry but I love watching these videos even though I don't understand most of it

[@NileRed]

+War Oliv I am glad you enjoy!

[@Edward55221]

+Nile Red Question, is it reasonable to say you Could effectively learn chemistry as an amateur or for a hobby without formal education and little to no experience? I've always wanted to learn but was never required to.

[@Edward55221]

***** Thanks for the reply, it will give me somewhere to start at least! And yes, I definitely understand that comprehension is key to learning, as with most disciplines. Thanks again

[@Shouttz]

I might just start reading some on my free time aswell, thanks for the tips Mikael

[@loganmante3321]

+Edward jfdlaj you can definitely learn chemistry in unconventional ways like KZbin or just teaching yourself. I actually have taught myself over the coarse of about a year from videos like nurd rage and here and the Internet and currently have a small lab in my backyard. The one drawback though is that chemistry is not cheap and people will start asking you questions if you advertise yourself

[@jennablue5763]

As a pharmacy student I gotta say that I adore your videos!!! They keep me motivated to study, you make chemistry so beautiful.

[@alnoiseplaysmc]

5 years later can we get an update? You a doctor yet?

[@jennablue5763]

@@alnoiseplaysmc I am so surprised you asked for an update, and my answer might not be what you expect, but, here I go. When I made this comment I was actually going through depression due to me being sexually assaulted at 18 (when I posted this I was 19). I couldn't get out of bed and every day was a constant fight to live. The only thing I felt like doing was chemistry, I remember spending hours and hours studying it. In spite of that, I lost 2 years of my life because of depression, I failed every exam, no matter how hard I studied, but still, I kept trying and I never quit my degree. I am now no longer depressed, on my third year (in my country it's 5 years to get my degree) and I am going to keep working hard until I can get my doctorate. Still, it's going to take quite a while because I'd like to first do my masters and find something I am really passionate about researching, at least 4-5 more years. Also, I think that I will keep studying even more to become an actual doctor, because it annoys me that in spite of all my knowledge about drugs, how they work, and interactions, I can't prescribe them but doctors can. Thank you for asking, sorry for the long answer. I hope you have a lovely day!

[@jacobkudrowich]

@@jennablue5763 pharmacists are gay.

[@jsutinbibber9508]

@@alnoiseplaysmc @jennablue5763 any update?

[@mrchangcooler]

Loved the explanation, I'd like to see more in the future.

[@NileRed]

+Mr.chang cooler Thanks!

[@bimbumbamdolievori]

You explained it so well it looks obvious and simple afterwards.i appreciated how you got into details as for the oxygen being more greedy on electrons and therefore pulling more and letting the rest "uncovered" . Loved it . I know more

[@896thomson]

I really enjoyed the detailed description of the reaction and it's mechamism. Great video as usual, keep it up!

[@Mdsde]

I learn more from KZbin than I did with 2 semesters of Chem. Not my teacher's fault, he was a legend, but the syllabus must be taught as is, and Highschool Chem was not about how much knowledge you had, it was about how you portrayed that knowledge in EEIs, ERTs and tests through your writing. Also your videos are great, you stick to a nice rigid report style format which I enjoy a lot.

[@loganv0410]

Long But not long-winded Great explanation Logan, ChE 1981

[@NileRed]

+loganv0410 Thanks!

[@NileRed]

***** i am finishing editing that today, so it will be soon :)

[@seannot-telling9806]

I for one don't mind when the time is takes to explain something in more detail. Thanks

[@giansieger8687]

NileRed Why can‘t the aldehyde be reacted with ammonium chloride to not have an „unnecessary“ hydroxy group?

[@DjNaphthalin]

Great synthesis! Your examples and methods are really helping me in my apprenticeship in chemistry! Keep it coming :)

[@JaySmith-cd1ln]

Cool! I haven't seen down into a vacuum filtration thingamabob before :) Love the channel, keep it up!

[@mateusbmedeiros]

Wow, feels so weird coming back to this one now after the successful transformation of gloves into spicy sauce.

[@its_raksh]

I wish people teach like you ..so that we don't learn chemistry only to clear some exams but to apply them too

[@gravitycat4777]

Enjoyed this particular one a lot due to the extra info. Not overwhelming at all. I'm a senior Chem Eng and all this pure chemistry stuff is quite rusty in my head (you know, for us A + B gives C and that's mostly it :D), but you manage to make it fun and enjoyable. Keep it up! Best regards from Spain.

[@MrDeathray99]

The explanation was really in-depth and helped me understand the reaction a lot better, thanks.

[@sleepful1917]

wow that editing at around 3:53 was so smooth and nice to see lol

[@vance7354]

I would love to see a Series that goes in depth on the fundmentals of chemistry, that covers techniques, fundementals, terminology and basically simple explantions of all the things like buffer solutions, etc

[@louiesatterwhite3885]

1:57 Could have reacted the vanillin with ammonia to form the corresponding imine as an intermediate, and then used sodium borohydride to reduce it to amine. I have performed an analogous reaction to this, but with p-toluidine to form a di-substituted imine.

[@silkyz68]

I would really like to see a full conversion from vanilla to capsaicin

[@AlexG-dt3gn]

@9:14 it's a strong independent molecule and don't need no bond

[@LinhPham-4568]

I did this. the reaction works very well. thanks a lot

[@multixmatrix]

I am student at industrial and applied chemistry department at port said faculty of science in port said Egypt , and I am really making a good use of your videos in my studies , So thank very much. I am hoping that you upload the synthesis of luminol because I am planning on making it myself at my collage's lab and your experience through that video will be extremely beneficial to me and will help me in making it.

[@barriehemming1189]

Hey Nile you could probably go straight to the amine, via a Leuckart reaction, similar chemistry but with a H+ addition.

[@transistortester]

Very interesting as always, you do a great job explaining what's happening. My votes for the videos are the effects of acid on skin, and nitrous oxide.

[@flame3723]

honestly i think this video helped me understand double bonds better

[@tvtvvtvt8017]

Little correction: purpose of the sodium acetate is to deprotonate the hydroxylamine hydrochloride’s proton so that the nitrogen which is initially tetravalent, then after deprotonation it will now have a lone pair on the nitrogen which it needs for the first step of the reaction mechanism where hydroxylamine nitrogen attacks the carbonyl carbon of vanillin.

[@Kumquat_Lord]

The madlad finally made his hot sauce

[@matthewfyson6809]

This video is in the pre-lab for a practical I have to write up on for a coursework resit.

[@Atomos95]

+Nile Red Very good job this time! The procedure is correct and big yeal result. This time you hit the center!

[@Mezuzah87]

Awkwardly condescending...

[@Hasan-cu5sd]

It's 2019 still didn't upload hydroxyl amine hydrogen chloride video

[@MrRubiksCube657]

If you get the Vanillylamine reaction working, then you should try and synthesize capsaicin in a video

[@chemistcraft3007]

Here from his synthetic hot sauce video - he did it! He completely synthesized nordihydrocapsacin almost entirely from scratch!

[@PaulaBean]

Have you ever considered doing a series of videos about extracting essential oils and fragrances from natural products, and creating simple homemade perfumes and lotions with them?

[@LFTRnow]

What happened to your plan to synthesize capsaicin?

[@austinwolfe7295]

This reminds me of the Admiral Fitzroy Storm Glass. Please do a review or chemistry break down on these! They're super fascinating

[@daniellamaster9000]

You should be able to reduce the oxime with zinc dust and acetic acid as the solvent. It may require some heating. The Knorr pyrrole synthesis uses this method to generate alpha-aminoacetoacetate esters in situ.

[@Mattes_______]

Nice video as always :) are you going to show yourself in your Q&A ?

[@furinaメpininfarina]

Nice one.

[@angelaricks5379]

I'm subscribed to you for more videos and because I love you. 😎

[@MechaTehDark]

Do you still plan on releasing a video on the synthesis of Hydroxylamine HCl?

[@NileRed]

+MechaTehDark yup

[@doctornobody6845]

@@NileRed how's that coming along?

[@Cristi0986]

@@NileRed please anwser me.you didnt make the capsain video?

[@saberbraik5858]

Good job Sir :) keep going :D your fan from TUNISIA

[@a2pabmb2]

*sees vanilla* I wonder if I can make capsaicin with this? Truly a mad scientist.

[@satyabrata8371]

Please upload videos on synthesis of vanillylamine.

[@tdoge]

You should do the step by step explanations more, with the intermediates and all. It really helps for understanding these reactions, and chemistry in general. No explanation is too long, usually.

[@lukebowers536]

Excellent explanation NileRed, are you gonna get round to synthesizing a capsaicinoid at some point ? I want to have a go here in the UK as we cant by PAVA powder any more here & like it becuese i get the hot sensation without any of the stomach upset, ive got the lab glass & chems to do it, ime just not confident yet in my method & dont want to mess it up, it would be good to see a work up first before i try it & no one has done it on here yet.

[@TheSnakeboy11]

I'm majoring in chemistry solely for the purpose of understanding your videos

[@mathewrodriguez5914]

You should make a video from the Williamson(or William) synthesis

[@noahd8673]

Plz make more videos about this stuff!!!!

[@luisbeaucage5147]

Nile, do you think you could ever show us how to make sulfuric acid? Here in Canada it's cheaper to buy the Sulfur itself rather than the sulfuric acid...

[@spidaxtreme]

Rona sells sulfuric acid as a drain opener (Super Drain), atleast here in BC. It costs about $10/L

[@capsinplace]

great video again , any chances of making a video regarding sodium azide ?

[@mmmhorsesteaks]

wouldn't Leuckart-Wallach be easier than trying to reduce oxime to amine? oximes generally form hydroxylamines upon reduction iirc. I would be interested to hear what didn't work, too.

[@pietrotettamanti7239]

Lithium aluminium hydride apparently can turn hydroxylamines to amines.

[@maxresolution1495]

you're awesome! can you do a video on crystallization of solutions?

[@loganmante3321]

For the q and a I would love to hear about why u do chemistry and how u got involved I would like the effects of acid soon

[@TomsLab]

Did you try to reduce the oxime with sodium in anhydrous ethanol?

[@nicolasfincias8]

One question : What were your ways to reduce the oxime into an amine ?

[@giansieger8687]

I thought stannous chloride should work well but idk, maybe he tried formic acid

[@sorsorscience0787]

Can you make a video on boiling household vinegar and ammonia to make a stronger chemical?

[@JoseOrtiz-yv8jz]

Will you make a video on the synthesis of capsaicin ??? I would really want to see that

[@GolferBowles]

Hi Nile, love your videos. Have you tried synthesising vanillylamine by reacting vanillin with ammonium formate instead of forming the vanillin oxime intermediate?

[@YuPuWang]

As a side note, many oximes are used in fragrances and flavors. I've read a Perfumer & Flavorist article about this topic and found it interesting that the smell of an oxime and its parent aldehyde/ketone have no correlation at all. Oximes of aliphatic/monoterpenic aldehydes tend to smell green/grassy and (as I recall it) jasmone oxime has a vanilla/gourmand type of scent. Now I wonder if you've got a chance to smell your vanillin oxime product. It should have a (strong?) odor completely different from vanillin, but I can find no info about its odor whatsoever on the internet. Maybe if you still have some in hand you could try making a 5~10% ethanol solution of it and spray onto a piece of paper or your skin? Let us know the result!

[@Mortiis558]

Why would one use an oil bath instead of a water bath? Hotter temp with less evaporation?

[@elephystry]

Mortiis558 think so

[@AsmodeusMictian]

I was wondering the exact same thing, actually!

[@spiderdude2099]

If you need to heat anything hotter than ~80 degrees C its preferred. Using a water bath at 81-100 degrees C isn't desirable. Obviously at 100 C it starts boiling and even below that , it generates a lot of steam. This is especially bad for any reactions that need heat but no water present even trace moisture in the surrounding air. Also any reaction that needs temperatures hotter than 100 degrees will absolutely require an oil bath. Most can go upwards of 250-350 degrees without boiling, burning, evaporating or decomposing. Additionally, a majority of reactions performed in research labs require 12-24 hours to run. A water bath would evaporate much too fast even without any other complications. Water baths are usually best to use for gentle heating of vials or flasks to remove a volatile solvent from a sample such as ether, dmc, ethyl acetate, acetone or hexane. (Boiling points 70C or lower) in fact in my professional work I've only seen water baths used to heat flasks gently like on a rotary evaporator or to incubate biological samples at 40-60 degrees. In general water baths are not often used as the primary type of bath to actually carry out heating reactions directly. Oil baths or heating mantles are the gold standard for providing even heating and thermal energy to initiate reactions

[@AlldaylongRock]

why ujust didnt use ammonia to turn the aldehyde into an imine and then reduce it to give the amine?

[@bunnyfaceperson123]

he wasn't trying to make the amine

[@jacobdehovitz156]

not in this video but he was trying to eventually get to capsaicin, meaning he had plans to make the amine.

[@travisfu8791]

you could also react with ammonia and NaBH3CN at acidic conditions to skip a second reduction step.

[@zacharysinger5370]

Reduce the oxime with Na/Hg amalgam or NaBH4.

[@GranRey-0]

Did the salt stay part of the solution then? At first I thought that was what crystallized lol

[@davidnahmad9405]

Nile: I want to make a transition from a ring structure containing an OH double bond to be substituted by an CH3 and keeping only the O in the ring. Any ideas?

[@ronjohnson8248]

12:03 You did it because you have Cody Envy... :)

[@skydivertyler]

So I know this is a dumb question. Will it taste vanillin-esque or spicy?

[@NileRed]

+SkydiverTyler The oxime?

[@skydivertyler]

Nile Red Yes, vanillin oxime.

[@NileRed]

SkydiverTyler It wont be spicy. Like vanillin, it will probably just be super bitter

[@elephystry]

NileRed E d i b l e C h e m

[@reinderdevries3026]

Have you tried zinc/AcOH reduction? is generally very efficient for synthesizing amines from ketoximes

[@tmfan3888]

when will u make the other part of capsaicin? (the carboxylic acid part)

[@alllove1754]

Since you like smells... how about these for esters: methyl fulvate or methyl humate? Not to mention any alcohol..

[@arynees]

Did you try using lossens rearrangement to make the vanillin amine

[@alanramos8229]

must do this

[@gregoryhonebay]

You should make a video on making cyclohexane from benzene ! Cheers

[@chantalroman6068]

Acetone from calcium acetate would be pretty dope!!

[@elephystry]

chantal roman think he did that c:

[@ebrudogan6417]

I dont know why I'm watching this video but I dont regret it

[@Cristi0986]

when do you make video with hydroxylamine HCL?

[@elephystry]

ionel anonimul eventually xD

[@MisterRazz]

@6:04 is there a reason why you didn't use hydroxylamine solution (50 wt. % in H2O) instead of the salt? Maybe I'm missing something here, but I believe this would remove the need to add the sodium acetate to sequester the HCl.

[@MisterRazz]

Never mind! The slightly acidic conditions are required to catalyze the reaction!

[@thisisnotmyfinalform7856]

Can you do a synthesis of any vitamins??? please respond

[@NileRed]

+marcel fernandez I want to but they are all so complicated :(

[@thisisnotmyfinalform7856]

+Nile Red you a smart guy who has done biochemistry and loves organic you will figure it out.

[@gc6329]

Vitamins are gigantic molecules and not super interesting to a broad audience so I doubt he would but I'm sure you can find plenty of others who have done it

[@kingsalomo5638]

Have you finally had sucesss with the capsaicin synthesis?

[@pcmasterwraith7676]

ever gonna try to make very fast death factor

[@CzarownicaMarta]

Yeah, that would be a nice one

[@andrew6464]

2:28 now that’s a mouthful

[@princ3_charl3s12]

Are you still working on the capsaicin video? As in trying to successfully get the 2 "ingredients" for it like this one?

[@princ3_charl3s12]

Actually Vanillin Amine not this one my bad

[@NextGenAge]

Please do a video on how to synthesis Anhydrous Aluminiumchloride from Zinc Chloride and Aluminium powder! It such a useful but hard to obtain chemical :)

[@NileRed]

+NextGenAge I might. I think ChemPlayer actually did this. Have you seen it?

[@NextGenAge]

Yes, but I think yields can be improved and the lewis acid is really useful so it is always a great addition. I also searched for a synthesis of LiAlH4 but that's too hard.

[@christopherjose922]

Why not just doing Vanillin Imine and then doing a reduction to get the amine?

[@WaffleSmoof]

THE SULFURIC ACID WHAT HOW WHY NEED TO KNOW.

[@oceanjunkie5968]

+WaffleSmoof I'm going to guess that it is because the sulfuric acid is not ionized very much at high concentrations.

[@WaffleSmoof]

But isn't highly concentrated H2SO4 at 98%, and isn't there some moisture in his hand? And i saw what it did to that paper towel which is an organic compound. And Martin Polikov Said that is should do the same thing to all organic compounds, so how is any of this happening

[@sbreheny]

+WaffleSmoof I'm guessing that a few things are going on here. First, the very top layer of the skin is pretty inert and dry, so it probably takes some time (30 seconds maybe?) for the concentrated H2SO4 to eat through that. You can see that the top layer of his skin does discolor slightly. I think he probably rinsed the acid off in less than 30 seconds. Secondly, the main danger from sulfuric acid is getting it in your eye or on some spot on your body that you don't initially notice until minutes go by and by then it has begun to burn through the lower layers of the skin and you have much less time to react.

[@WaffleSmoof]

that works for me thanks :)

[@fpm1979]

+WaffleSmoof Maybe he cheated. It wasn’t sulfuric acid. Or he applied a protective layer of balm to his hand. Or he is naturally inert to sulfuric acid.

[@amkaktiv2886]

Why not use Sodium or Lithiumamide and then an reduction of the OH groups?

[@dakarpsi]

Vanillin from oak wood would be interesting.

[@TheHashCode]

any chances on a sodium azide video?

[@rocknrollmanic]

Idk if this would work but I know it does for methylization and demethylization. Iodine. Iodine bound to an amine may do the trick.

[@jakenbaked87]

What stopped you from doing reductive amination to vanillin using NH3 and Al amalgam?

[@DPDeLima]

Very nice an informative video. Congratulations! Have you done the reduction of the oxime from vanillin?

[@Pwn3dbyth3n00b]

So been waiting for half a decade now. Did he actually make capasacin?

[@Hume820]

Did you measure the mp of your product? 82% yield may actually be much lower. Maybe recrystallizing it may help before attempting vanillylamine.

[@NileRed]

I actually did and it was almost exactly literature or 1 degree below I think.

[@Snyper1188]

I saw the video of you putting different acids on your hand, but I can't find it now. I wanted to show a friend. Can someone link it for me?

[@pshejwalkar2004]

Why don't you make an imine and then reduce it with NaBH4?

[@LinhPham-4568]

did it work well when reduce imine into vanilylnamine with NaBH4? do you have any documents about it? I'm going to do it this way thank you so much

[@benimben6972]

​@@LinhPham-4568what is the result?

[@baberoo3898]

I’m not trying to be rude I swear, but shouldn’t the nitrogen in the first intermediate around 9:17 have a positive charge since it has two hydrogens, and oxygen bond, and a carbon bond?

[@solarwarriorkek]

Why not stoichiometric amounts of reagents?

[@alansoriano3533]

This is the Leuckart - Wallach reaction. Reductive Amination,

[@BGrab]

Ever tried an ozonolysis-reaction at home?

[@oogieboo1]

As someone who has no chemistry experience, I am confused by the unmarked hexagon in the molecule diagrams. What is that?