Preparing a Good Supporting Information

[@jackhinkley6162]

An interesting discussion. Being a retired old school medicinal chemist I have a different view on some things. The purity of a bulk sample should be as high as possible and homogenous. Mps should always be reported with recrystallization solvent or solvent mixture. The purity of a compound is not determined by HRMS but by elemental analysis (n = 3). A clean TLC, H-NMR, and an elemental analysis within the the accepted limits to calculated percentages (+,- 0.40% and better +,- 0.20% ) for each element is a requirement before submitting a compound for screening. Adjusting for H2O is acceptable but not for any other solvents which are usually toxic. Drying conditions dictate. I always required compounds to be dried at least 40 oC under high vacuum to a constant weight. I once prepared a known optically active compound with two stereo centers that had to be recrystallized to a constant rotation, even though the mp did not change and the elemental analyses were spot on, before it could be sent as a reference compound for an in house biological screen. Actually your discussion about consistency encompasses the format for the main body of a paper as well the experimental. I don't recall, however, that you said anything about safety issues that may need to be emphasized for a given reaction procedure. I also spent time chasing down literature procedures, but in the good old days we actually had to go to the LIBRARY and read hardcopy. (Patent literature is especially bad) I kept a notebook titled " Useful Other Things Found While Looking for Things". So, although I do understand the frustration, I am not so sympathetic to the need of spending all of 45 min on a search, unless it cuts into bar time. I think the logical extension of your video would be a discussion on how to keep a notebook,, what it should contain, and how detailed it should be, as it is the primary record of a given experiment. It might help limit poor experimental write ups. jmh PS The compound in the last example is a steroid.

[@That_Chemist]

Great suggestions and great comments! Thank you for your work in the field :)!

[@princessjd9462]

@@That_Chemist, thank you for your video, it will be very useful look at your tips how to keep a lab notebook!

[@gamingmarcus]

There's nothing more frustrating than having a paper say "previously reported procedure" which cites their own paper, which then cites another paper and so you end up going through 8 different references until you reach a synthesis reported in the 1950s which is a 50 page review and you can't CRTL+F in such an old paper so you have to manually scrub the entire document. I'm just very slightly annoyed at this.

[@That_Chemist]

its such a waste of our time as scientists

[@minklmank]

Oh this hits home waaaaay to hard

[@劉樂山]

Especially when the paper is not downloadable using sci-hub, it's frustrating.

[@stephenjacks8196]

Or the referenced paper needs to be translated.

[@gamingmarcus]

@@stephenjacks8196 Heck yeah. Nothing better than a google translated chinese patent you got out of the scifinder search.

[@koukouzee2923]

alternative title : how to not be in the toxic series

[@That_Chemist]

Virtually every SI has the problem of being inconsistent - it’s too big of a problem to throw everyone under the bus here

[@koukouzee2923]

yea I'm 5 min in and I'm understanding more of what the video is actually about xD

[@morrisdweck32]

As an academic chemist I cant stress how important a clear and detailed SI is. 95% of the time, I read papers only for the SI as I want to do a similar reaction in my own research and cant express my frustration at having to jump though so many hoops to find an SI only to find it lacks almost all experimental detail. Papers are for PIs, SIs are for your fellow chemists.

[@That_Chemist]

100%

[@trumpeteer240]

Also the absolute greatest SI i ever worked with was a paper with like 50 compounds synthesized, had a table at the top as a table of contents with what page to find each compound's prep and the NMR data and the spectra themselves in the appendix, I have promised myself to never make an SI without one of these from now on.

[@spiderdude2099]

The following things is a paper are surefire ways to earn my eternal wrath: “Was crystallized” …..no details of solvents or conditions for recryst “Was extracted” ……no details of workup or extraction solvents or volumes or which phase product should be in “Was purified via HPLC”…..you absolute cowards. Anything can be purified out on an HPLC, and usually it means terrible yields “NMR or mass spec confirmed identity of compound” …..no peaks or details, or spectra…..like…bruh. “No percent yield or mass of final product obtained” ……great, this makes it impossible for me to know how much to expect “No details for TLC or solvent gradients” …..how do I purify it then? Don’t even THINK of saying HPLC. “Was prepared from literature” …..what literature? What protocol? What conditions? There’s like….a million different ways “Rxn was run until complete as shown via TLC” …..no. Actual times. Give me hours or minutes, I’m not checking TLC every hour for multiple days. Also, what am I looking for on TLC? What conditions? “Confusing to find or nonexistent supporting info with all synthesis details” ….stop making this a hunt to find your synthesis notes “Having a chemical used as an intermediate without synthesis details for how that chemical was made or obtained” ….this is so annoying on scifinder, when some papers are the only source that used a certain molecule, but they used it as a starting material so they don’t have details on its synthesis or where they obtained it from…

[@That_Chemist]

I hate it when they say “until complete by TLC”

[@spiderdude2099]

@@That_Chemist I legitimately SEETHE. Bitch….HOW long tho…? I don't have ALL DAY to run TLC. Give me a ballpark.

[@spiderdude2099]

@@00bean00 we can't tell you what the methods are, but there are some...

[@Petemate69]

Yeah crystallised but no listed solvent, ratio of solvents, volume of solvents, temperature of rceryst, anhydrous vs HPLC grade solvents used. I could go on and on...

[@TheLouisph]

One of the things that annoyed me the most recently are papers that refers to other paper for the preparation, then you go on the other paper and they are also referencing another paper for the synthesis. A month ago i had to go to the fifth paper to find the real protocol, i was so mad

[@spiderdude2099]

I always include mass I weighed out AS WELL AS molar equivalents. Some people really like using ONLY mol equivalents, some people only like using mass, I think it should be AT LEAST mass, or both mass and mols. Never just mols. Some people say that mols are better because the ratios make it instantly scalable to any size prep, but I agree with you. Even if a general molar ratio is useful, include the specific amount you used specifically in this instance

[@BlurbFish]

It's a moot argument whether one unit of measurement is "better" or "worse", as we're not restricted to only reporting one or the other - what matters is whether the unit of measurement is useful or not. Moles are very handy for modifying a reaction to different substrates, but mass (or volume) is strictly necessary in order to reproduce the work. To anyone saying it's not necessary I say they can convince me by counting a mmol of their starting material. In short, it is good to report moles along with mass and/or volume.

[@PeLuRu4586]

I love it when they: 1/ State the honest yields of the reactions. Or at least give some reasons as per how some yields are low. 2/ Give the damn Rf value (come on it's not that hard???) 3/ Give the spectra with clear resolution. Even better if they give clear assignments for every compound as well (our group has the protocol to give full assignments unless some papers ask to remove them). 4/ Don't give us a mini-scavenger hunt game for the references within references within references. The list goes on 😂

[@wabibunny]

this is super funny because our teachers in the undergrad labs always tell us to report every minor detail... and yet i fail to comply. the thought that keeps me on track when i fail is: if i wrote a paper about this right now, would i have all the info for some other student that read it? *would they reference it?* :p

[@gmcenroe]

As a medicinal chemist in industry we always used electronic notebooks. I was a stickler for details in my EN and included as much info as possible including LCMS runs on reaction mixture while observing progress of the reaction, pictures of TLCs , chromatography run on automated normal phase including plot of separation, 1H-nmr spectra, final HPLC purity, x-ray structure for new chiral compound if possible. Since we use EN we could also look at any EN page for other chemists, search their notebooks. Our nmr used to automatically transmit crude spectra to our EN, but we were supposed to workup the spectra and report chemical shifts, splitting, integration. It used to drive me nuts when I saw some lazy chemist notebooks , some who did not speak or write English well who would simply show a reaction scheme and final amount of reported yield, never workup spectra or report references. Their supervisors were to buy playing politics and attending endless useless meetings to check on their work. Often one experiment in my notebook could end up 20-25 pages. I'm sure that the patent lawyers appreciated it!

[@lucasmele397]

Denmark group SI are for me the best examples of consistency in writing detailed procedures

[@That_Chemist]

Post some examples in the excellent papers channel in the discord!

[@wabibunny]

please do post them, i'd like to see them before writing any SI of my own :p

[@lucasmele397]

@@That_Chemist Sorry for the delay ! Just shared it in the discord (maybe wrong channel, feel free to move it if so !)

[@lucasmele397]

@@wabibunny Just did it !

[@nathantang9964]

I don’t think reaction vessel really matters unless it’s a special thing like a sealed tube. What I think does matter is not just reporting what the product elutes at but also the gradient.

[@trumpeteer240]

I will now refer to people as nuggets, so thanks for that, also my favourite is purified by FC and not giving a system so now i spend 2 hrs trying to find the optimum system by TLC.

[@That_Chemist]

It’s the worst when they don’t give you that

[@mathiasdaniels651]

This is a nice summary of a topic that many people have a different opinion about. Only Organic Syntheses will have really comprehensive procedures. Details like reaction vessel are almost never reported, I only write it down if it is something other than a round bottom flask. I personally think it is acceptable to refer to papers for the procedure and characterization data if it has been reported before and you were able to reproduce that procedure (if something is changed I would write "modified literature procedure" and write the details and add the original reference). About what data should be added, it really depends on the type of work and the journal. A characterization checklist like ACS has, is really useful, and I think should be added in every journal because it gives a good overview of the techniques that you can use. For most organic synthesis work, the proton, carbon and other nuclei NMR + HRMS is about the minimum. Melting point can be useful just to know if it is easy to melt and it can be an indicator for solubility, but it can be difficult to get consistent data as some compounds have several polymorphs and if you don't use a DSC, it can depend a lot on person performing the analysis and even the machine used. I think FTIR is useful for compounds with some functional groups (azide, nitrile,...) but in al lot of cases, the fingerprint region is too crowded and the results can be influenced a lot by the person performing the analysis and even the weather (huge water bump in humid places). I think that a technique like X-ray is quite good if you are preparing a new class of compounds or identifying natural products/specific isomers, but it can be difficult to get a suitable crystal. One thing that you didn't mention is UV-Vis, I think that this can be quite useful for a lot of compounds especially if they are coloured. My comment is getting rather long, but one final thing. Reporting rf values can be a bit tricky as those can often be influenced by things like manufacturer of the TLC plate, thickness, glass or aluminium foil, filter paper in your chamber or not, size of your chamber, was it closed well, how much solvent, temperature in the lab,... It would be nice to report every detail, and that is also why I like Organic Syntheses a lot, but sometimes it is just not feasible. Thank you for the video, your channel is publishing a lot of nice content recently and I enjoy it a lot.

[@That_Chemist]

What I will say is that many of the things that I criticize, I am personally guilty of in my own papers. I do often have more stuff written in the way I prefer earlier on, but when your PI asks you to change what information you include, what can you do...

[@That_Chemist]

I haven't had significant differences from TLC Rf compared to the lit - if they report it has an Rf of 0.25, its usually somewhere between an Rf of 0.2 and 0.3.

[@mathiasdaniels651]

@@That_Chemist I noticed during my PhD that my TLC of a reaction that I did many times before looked quite different when we had ordered glass TLC plates because the supplier ran out of the aluminium foil ones (same manufacturer, same thickness,..) but it can give an idea what to expect. I'm usually already happy when a paper reports their column solvent and I can just use that one for TLC

[@That_Chemist]

@@mathiasdaniels651 true - that is usually my go-to strategy as well

[@Medchemist277]

Something I want to add that including the assignments for your NMRs of the structures is so important! Sometimes I have to spend hours running through someone’s NMR to see if my product’s NMR is similar and even worse if they do not include COSY, HSQC, etc. If this was common practice, imagine the educational value (answers are provided and can test students ability to elucidate structures and they check their work).

[@louisminion9927]

Great video! Optical rotation can be really useful for some of us who work in chiroptical spectroscopy but tbf it’s not relevant for a lot of o chemists

[@oxfordtiger]

We were taught not to include information about what apparatus was used unless it was something unusual. I wouldn't normally include volumes of solvents for extractions and washings etc. I also wouldn't usually include quantity of silica used in a column - I hardly ever see that and wouldn't normally even measure! Solvents used should absolutely be reported though. TLC Rf values are a very useful addition. It is super annoying when someone references a compound and then you check it and it also doesn't have the prep for it!

[@That_Chemist]

IMO if you want to reproduce a procedure, especially for workup, its really important to have relative amounts for washes/extractions

[@gamingmarcus]

@@That_Chemist I'm guilty of this myself because I never measure that stuff. But washes in perticular are *always* in such a giant excess that it really doesn't matter. If you're working on a couple mmol scale and pour in fully concentrated premade solutions for neutralisation you'll always be in a hundredfold excess. Same thing pretty much for extractions. So many compounds you can dissolve 0.1-0.5g/ml solvent. So who cares it it's 10ml or 30ml per extraction if you're on a couple hundred mg scale? It's a giant excess, especially when talking about aqueous extractions where the product definitely won't dissolve.

[@TheLouisph]

@@That_Chemist I mean doesnt everybody but interns eyeball it anyway?

[@nathantang9964]

I totally agree, no one is actually measuring work up washes ever, maybe there’s an approximate that you can report but unless it’s really specific I would report such things. I would report how many washes though

[@oxfordtiger]

@@That_Chemist I agree that all information like this is useful when following a prep. I think when I learned this stuff, it was when most preps were written in the paper itself, so the emphasis had to be on concision. Now, most preps are in the supplementary info, so there is basically no such limit. I worked at a company briefly, and there they wanted everything written - apparatus used, quantities used in extractions, amounts of silica gel. Not only that, but also the chemical supplier for all solvents and reagents together with their batch numbers and so on! It drove me nuts - one of the reasons I didn't last there long!

[@janvisagie231]

IR is pretty good for identifying the presence of certian functional groups that would be hard to detect otherwise...azides being a good example. I'm nitpicking but yeah 🤷🏼‍♂️

[@That_Chemist]

yeah

[@Petemate69]

Easy enough to determine shiftsin 13C NMR based on where the azide substitutes. Reich collection has a really good shifts guide for 1H/13C NMR for a vareity of functional groups. Alternatively TLC the Azide by first dipping in DCM with Triphenylphosphine (staudinger reduction) for 30 secs before dippiing it in ninhydrin stain for 15 secs and char. Azides reduce to amines and clearly visible via amine stain.

[@mmmhorsesteaks]

I like FTIR. It's nice and easy, and usually a good sanity check. For crystalline products, a melting point is only really useful if you mention which solvent it was crystallized from. Pet peeve from my old lab ^^

[@porphyrin2290]

I suppose a melting point of dried solid is a much better than crystalline solid??

[@mmmhorsesteaks]

@@porphyrin2290 the issue is that the crystallisation medium can have an impact on the crystal shape. Usually if you measure the melting point it's after recrystallization; so you should know and report the solvent.

[@Qwayta]

Also, if you report a single crystal structure do powder XRD as well to check if the bulk phase corresponds to the phase measured by single crystal XRD.

[@uiucchemistry2664]

Solid video! I agree with lots of points here. Also, still hoping for a video on journal publications, impact factor, etc. from the comment/question from the Q&A video 👍

[@That_Chemist]

I need to do a proper full series on this - I want to do it properly though, so it may be a while

[@uiucchemistry2664]

@@That_Chemist Oh okay! I didn’t think you had so many ideas to make a series out of it. I was expecting maybe a longer 15-25min video but I’m sure you have a lot to talk about then if you want a mini series on it. Thanks 👍

[@rudolfmueller9145]

Thanks for this video! I told my guys a million times to do this right so that another person can just print the procedure and follow it exactly in order to make the desired molecule (or if they have to make more themselves). So many people are just lazy and do not write down what they did, then forget everything and make up procedures afterwards for publications. How easy would it be to write down the solvent mix/gradient for chromatography?! ......

[@jaredlowe3927]

This is the scolding I need everyday. (Guilty of not providing rfs, lol)

[@That_Chemist]

Same

[@Kready44]

ee is not a good value to describe the selectivity of a reaction, since especially when doing kinetic resoultion you also need to report % of conversion.The selectivity constant s=kR/kS is the better value to give

[@porphyrin2290]

elemental analysis and melting point are solely for purity purpose, and of course specific rotation for chirality purity (you need both R and S of exactly opposite rotation for sound argument). while other stuff like NMR, HRMS, GC cannot support purity, they give structural information.

[@That_Chemist]

but they are accepted interchangeably - you are correct though

[@porphyrin2290]

@@That_Chemist That really depends on the reviewers. I have met reviewer who love m.p. so much and asked for evidence of decomposition before melting during melting point test. Eventually I have to go for a TGA.

[@kalamatej]

I wonder why quantitative NMR is not commonly used these days?

[@porphyrin2290]

@@kalamatej quantitative 13C NMR takes very long measurement time on a 400 MHz machine, especially with quaternary carbon of long recovery time. It can be more convenient to submit sample for EA or HRMS.

[@armands932]

I am not sure about the best practices, but my supervisors have never asked or even mentioned providing reaction vessel in SI unless it was for a specific purpose - pressure vial for heating above boiling point, or steel reactor for hydrogenation under pressure.

[@That_Chemist]

stirring dynamics can change and impact stuff quite frequently

[@armands932]

​@@That_Chemist Maybe I need more experience to encounter a reaction that was impacted by stirring dynamics, I have had no problems with heterogeneous mixtures, except for when mixture properly solidifies into a brick. In that case I don't know how vessel shape/type would have helped.

[@rudolfmueller9145]

l totally agree! All details how a compound was made have to be in the experimentals. l find it highly annoying when the crucial step of cleaning up the mix is not described. How can anyone not show the chromatographic conditions, mp or optical rotation for a compound?

[@tylerswanson6358]

I could be overgeneralizing, but I think most journals these days are cool with chiral HPLC in place of optic rotation

[@vmodsm]

Rf values probably the most informative info other than physical appearance IMO

[@AlphaNumeric123]

I could not agree more! I’ve done this and felt dorky and like I was over specifying but it makes so much sense. I have no idea why SI texts are so tight lipped. Hope this gains traction

[@Treebark1313]

1:37 "... some journals don't require this. Those journals are wrong." 🤣😭

[@That_Chemist]

Yep

[@I_XuMuK_I]

Always pains to hear everyone talking about NMR like it is just given. Sadly not everyone has one. We have to ship our samples to another city and wait weeks to get the results. So we can only afford to do NMR on the most important compounds. Sorry guys, we are poor.

[@That_Chemist]

That sucks :(

[@TheMalena99]

Oh wow, never thought its wasnt a given :/ we have like 5 nmrs in different sizes and one we can even shim ourselves. Really brings stuff in perspective

[@yuriikovalov84]

Very useful video. I am glad that it will be useful for future generations... maybe even for decade

[@That_Chemist]

I appreciate your kind words :)

[@iryanmadayana1904]

That dreadful sentence when you want to reproduce a synthesis from a paper... "The crude mixture was separated by column chromatography." No solvent mentioned, not mentioned whether it is silica, alumina or reverse phase, nothing. And then you spend an hour trying to figure out how you are supposed to do things with TLC tests. And then you do the column and it turns out it was the kind of column where the TLC betrays you. 🙃

[@a_8764]

Regarding workups, I usually do extraction with ethyl acetate/diethyl ether three times and wash with brine out of habit and then column if necessary. But this is only because it's what I've been taught in undergrad courses and I haven't really considered it much more than that. Should you do extractions/washes if you plan on running a column, or do you just concentrate the reaction mixture and do the column straight away?

[@That_Chemist]

I think brine washes usually don’t accomplish too much, especially if you dry with Na2SO4 or MgSO4, but sometimes certain aqueous washes remove junk which would thicken your band on your column when you load, or they just make it harder to dry-load on Celite/silica. Some reactions I would just dry load the crude onto Celite and run the column like normal, but sometimes this isn’t practical

[@YuPuWang]

One thing I always hate is that someone thought they gave 'useful' information but they didn't. Seeing something like "nearly colorless" or "with a characteristic odor" for the physical appearance of a compound always irritates me. So you told me it's close to white in color, but not RGB=(255,255,255). Is it yellowish? Reddish? Bluish? Or what? And you told me it has an odor but WHAT ODOR? Is it fruity, fishy, petrolic, pungent, or what? If you can't provide certain piece of information with enough detail you'd better leave it out (unless it is required, of course)!

[@That_Chemist]

I absolutely agree

[@socratesm.5632]

I agree with almost everything you said, except that Combiflash, or Teledyne to be precise sucks!! Poor customer service, even worse attitude and way worse prices!! Biotage is the way to go. Professionality all around.😎😅

[@That_Chemist]

you need to get to know the Teledyne techs - Jack Silver is awesome

[@svenjanner5224]

Optical rotation measurements are still important in natural product synthesis (sadly)

[@user255]

A paper: We used modified protocol based on blaablaa1. Blaablaa1: We used modified protocol based on blaablaa2. Blaablaa2: We used modified protocol based on blaablaa3. ... BlaablaaN: We used very standard thing from 1986.

[@That_Chemist]

100%

[@jjgamboa91]

Try 1910 or 1933 for tritylphosphane derivatives

[@torako_torako]

From 1886, in german, not available online

[@dangerdackel]

Always get a M.Pt. Regardless.. it can help with polymorphs

[@jeffreyblack666]

I disagree with the idea of having a standard agreed upon of what can be included and enforcing that and not allowing extra. I think extra information should always be permitted in the SI.

[@Kall1208E]

The moment you start hoping your SI doesn't show up xD

[@That_Chemist]

I just chose examples from 8 of the first 10 that I had on file (from any SI's)

[@dasbuj]

Maybe I'm just a bad chemist, but I can count on one hand the number of times I've followed a lit prep and didn't have to spend tons of time modifying the synthesis to get pure product or get product at all. I write SIs to include every bit of strange information I saw that might help someone who might have to run that synthesis. Think of the poor grad students when you write SIs!! Lmao

[@That_Chemist]

100%!!

[@עידודומב]

What are the method for determination of D.r? Great vid!

[@That_Chemist]

HPLC? I haven’t done this personally, but I know lots of ppl who do this - you could always ask in the discord

[@עידודומב]

@@That_Chemist what do u mean discord?

[@foc2241]

11:38 this is a requirement for me... :D

[@dangerdackel]

Look in oprd on how to report reactionS and purification conditions

[@That_Chemist]

post a good one in the discord awesome papers channel!

[@oskarwasiuk1215]

As a student i feel called out 😂

[@ajyui847]

I have a question , is it necessary to get a written permission from the person who worked on a specific synthesis so I can work with it to create a new compound ? For example I want to creat an alphaamino phosphonat from a published imine syhntised ! Or complexing an already syhntised compound ! Plz I need an answer

[@That_Chemist]

No, of course not!

[@That_Chemist]

If you want to patent stuff, then you probably should talk to someone about obtaining rights, but if you’re just making stuff in academia or personally it’s totally fine

[@That_Chemist]

Assuming it’s not a scheduled compound

[@ajyui847]

@@That_Chemist hmmm it's about a thesis work , and an article ! Some journals asks for copyrights or a permission , is there any that doesn't ask for it ?

[@dangerdackel]

What about Holcomb, chiral or otherwise?.

[@pelegsap]

I must say that your videos made me a bit nostalgic to my days in a research organic synthesis lab... any chance someone can do some simple organic synthesis as a side hustle without acquiring 1000s of $/€/c$/₪/¥/£/whatever? I can't afford to build my own lab like NileRed and similar KZbinrs (also might be illegal where I live) :-(

[@That_Chemist]

you should ask people in the Discord

[@sumitsaini4830]

Great video...❤️👍

[@aaaaa-yv1zr]

actually raw FID is still possible to falsify

[@That_Chemist]

true

[@Andy-wc5xw]

Another banger

[@minklmank]

"Crystals suitable for X-ray Analysis were obtained by recrystallization of the crude product" Well no sh** Sherlock but how did you pull it off?? I have a feeling that way to many of us have read things similar high blood pressure inducing

[@That_Chemist]

100%

[@karolus28]

cool

[@MatheusAFK]

The lack of information concerning the washes and solvents used in chromatography make me mad the most. I hate doing things by "feeling" especially when I just want to reproduce and obtain a specific molecule.

[@That_Chemist]

yeah :(

[@everythingexplained3226]

here;s one for the algo

[@EdwinGonzalez-vs9el]

New idea, how to do a good cover

[@That_Chemist]

Like a cover letter?

[@ryanatkinson2978]

TIL: just write it up, don't be a nugget

[@That_Chemist]

damn right

[@chrisboyall8602]

Don’t be a nugget 🤣🤣🤣