Hi all,

Long time lurker, first Reddit post for me.

I'm trying to synthesize glyceraldehyde carbonate by performing a TEMPO oxidation on glycerol 1,2-carbonate. I'm generally following the method of De Luca et al, 2001, Organic Letters (10.1021/ol016501m) using TCCA as the final oxidant, with 1 mole% TEMPO in DCM. The only change I made to the protocol is using a non-aqueous quench (EtOH + Na2S2O3), since both my reagent and product are water-miscible and sensitive to alkaline hydrolysis. The reaction mixture is quenched, filtered over cellite and evaporated.

The issue is I'm not seeing any aldehyde formation at all in 1H-NMR. Nothing is happening between 9 - 11 ppm. The only change is the appearance of a broad peak at 5.2 ppm after 20 minutes, which further widens and moves upfield to about 4.5 ppm with longer reaction duration (max 40 minutes so far). So far, I've followed literature wrt. reaction time, being 10 - 20 minutes at room temperature. A colleague advised overnight and heating, but that sounds harsh, since the nitroxyl radical is supposedly unstable above 15C.

Does anyone know what I'm doing wrong? Are cyclic carbonates incompatible with TEMPO? Any advice would be greatly appreciated!

What are people’s opinions on switching from med chem to process? I’ve been debating the switch for a minute, but not sure about likelihood of success/general career stability.

I’ve been in med chem in big pharma for about 3 years post PhD. I know I would likely be taking a step backwards career wise, but that’s okay with me. How would you rate the career stability? I feel med chem is very unstable especially recently, but not sure how this impacts process.

Today I scavenged a recirculated chiller which seems to have its coolant coil corroded. Is it possible to simply cut it out, replace it with a similar enough copper coil, soldered by someone with experience and refilled by a refrigeration technician or once they are gone, they are gone?

(Third world country where 2-3k for a new one is not pocket change). I expect to end up with lower performance/efficiency but our requirements are not as demanding on the cooling side.

Hi Pros

I use TlOTf to make a Tl metalate of a ligand similar to tris(pyrazolyl)borate, and then transmetalate the ligand to a first row transition metal chloride. This is done in the glovebox — I even put on a pair of XL nitrile gloves over the glovebox gloves while weighing out the <5 mg TlOTf.

Reaction occurred, and TlCl was formed, and I filtered it off with a pipette filter. This filter, and every single vial, pipette, stir bar, and kimwipe that comes into contact with the material both before and after I filtered off the TlCl gets tossed into a special thallium waste bag, that will be double bagged and taken out of the glovebox when the bag is full.

Realistically, the only possible way I could come into contact with any Tl(I) is when I take aliquots of the reaction solutions during the course of the reaction and prepare NMR samples of them. The aliquots have their volatiles removed, then redissolved in C6D6, and then charged into an NMR tube, capped, and electric taped. I use gloves or Kimwipes to handle the NMR tubes out of the glovebox, and when I am done with the NMR samples, I bring them back into the glovebox and they immediately go into the aforementioned thallium waste bag.

DESPITE the a) very small amount of Tl salts I am handling b) in the glovebox, and the c) the extreme improbability that my skin comes into contact with trace Tl(I) compounds on the outside of NMR tubes that I ONLY touch with gloves or kimwipes......I am still scared of Tl toxicity, particularly very low-level, chronic exposure to ug or ng of Tl(I) compounds through skin absorption (not much is documented about this form of toxicity, which may not even occur or present symptomatically.

The question is: am I good and safe? Is it ridiculous/unsafe to supplement prussian blue during the week(s) I work with Tl in the glovebox, in order to have immediate capture and release of Tl(I) that has found its way into my body? Has anybody heard any stories of chronic, low-level Tl(I) exposure causing any issues in anybody?

Thanks in advance.

Hello, I was preparing some benzylmagnezium bromide. I was cooling the reaction mixture in ice bath and it solidified like this. The solid won't dissolve. Any thoughts what could it be? I am thinking of potential water contamination and magnezium hydroxide or oxide forming in excess quantity..?

Hi everyone! As titled, can TPPO from a Suzuki Coupling using Pd(PPh3)4 interfere with a reductive amination using STAB in the next step?

TPPO co-elutes with my product. I am considering complexing TPPO with ZnCl2 or MgCl2 to remove most of it but would greatly appreciate any insight to know if I can get away without complexation.

Thanks in advance!!

Hi, I'm using peristaltic pump in flow chemistry, but after a complete wash of one of my pumps (because it was blocked), the flow rate is now almost two times too big (if my input is 1mL/min, I'm almost at 2 in reality). Does someone have an idea why? Thanks!

Hey everyone,

I have measured SAXS and WAXS of a series of cellulose fibers. These are the data integrated perpendicular to the fiber axis (where the WAXS signal is the strongest due to texture). Basically, they show a Lorentzian decay at low-q and Gaussian at higher q-values. Background was subtracted and data normalized to max intensity.

Although I know well what to do with WAXS data, I'm not very familiar with SAXS and unfortunately I have little-to-no-time to spend in studying all possible models and theory.

Please, can anybody direct me toward a good and simple model to fit these data and extract useful information? These are crystalline samples (not diluted). Perhaps a reference too.

Thanks!

Dear all,

one of the reviewers suggested that we determine the HOMO-LUMO energy levels of our polymers through the use of cyclic voltammetry determination of OX and RED vs ferrocenium couple. I have done literature research and as far as I've found, the work is done in solution or on conducting polymers. The problem I am facing is that the polymers we have are non-conductive. I am wondering if it would be okay to mix the polymers with conductive additive (carbon) and binder (PVDF) an drop cast it on the surface of the glassy carbon electrode and measure the CV of this composite.

If someone could turn me to some literature precedent I will be really greatful. Thank you all for your answers!

I run a transmetallation reaction with MeMgBr to replace a chloride ligand with a methyl group on my iridium complex. I've tried filtering out the Mg salts with celite (multiple filtrations) and still can't manage to remove all of them. I was told that dioxane could be used to crash those salts out but I haven't managed to find a good procedure and needed advice.

Thanks!

I ran some standards to calibrate the method we were using but we forgot to change the signals (we were using 3 signals and we wanted to add 2 more). We thought that we could recalibrate and reprocess the data of the samples we already ran but it won't update, the signals won't change. Are we doing something wrong or adding new signals after the run won't work? Should we run them again?

English is not my first language and I'm not used to using scientific language, I hope my question was clear

What is this for and how is it called? It's about 90 cm long.

The label says: "Scientific Glass Apparatus Co. Bloomfield N.J."

Thank you!

https://preview.redd.it/kn2q8sxqq5ge1.jpg?width=1500&format=pjpg&auto=webp&s=fd38a1131ffcb0c66937ba8f2ed4d93ca4cae4ec

Schematic

https://preview.redd.it/ogympl8we6ge1.png?width=485&format=png&auto=webp&s=07c96736d613d928779d7d2474f81f18d1071efd

Update 1/31/25

Valve schematic.

https://preview.redd.it/6wuklt2oudge1.png?width=600&format=png&auto=webp&s=566df592c71b260ebfc41b2ea091c02dc28f5b61

Just worrying about inhaling them if they dry on the counter for example. They are functionalized to be soluble in water. Using a fume hood is not possible.

There exist vacuum ovens that can reach 1200 - 1800 C. Some of those also have a gas inlet. Is it possible to operate these "like a Schlenk line"? So vacuum / argon evacuation while cold and then heat it up under argon? Is it effective at excluding oxygen?

The reason I'm asking is because I'm worried my reactants are too volatile under vacuum 😅

Hello!

I want to use sone anhydrous NaI for a fairly water sensitive reaction. The problem is that affordable commercial "anhydrous" NaI still contains 0.5 % water and 1.5 % of other, unidentified volatiles, and I use a huge excess of NaI, so I have to dry it.

The procedure I follow dries it in a heating pistol over P2O5 at 1 mbar in a sand bath at 250 C. That is doable, but annoying, and I was thinking there has to be an easier way.

Does anyone have a procedure for that?

The NaI is supposed to be used with 4 eq. in a halogen exchange to further activate a chloromethoxy group for a N-alkylation. The substrate hydrolysis in slightly wet DMSO, the product is stable. Solvent is anhydrous THF.

I was thinking of (partially?) dissolving it in MEK and distilling off the minimum boiling azeotrope to dryness, maybe multiple times, or refluxing it over molecular sieves in a soxhlett.

Is that worth a shot?

Or maybe just circle the water out with toluene on a dean statk trap, but I'm not sure if that would free the water out of the solid.

Also, does anybody have experience with KI instead of NaI? Is KI easier to get anhydrous or easier to dry?

If somebody has experience with that, I'd appreciate it. I'm currently drying it the old fashioned way, and the P2O5 is already clumping up, so i feel there must be a more elegant way.

Has anyone used sodium tert-butoxide in DCM? I can’t find any information on compatibility but my hands are kind of tied on solvents. Thanks!

We are running into an interesting contamination problem with dosing solutions with the flavor compound benzaldehyde on QQQ-GCMS. Our solutions are showing on our GCMS about equal responses for benzyl alcohol/4-methylphenol (?) peaks along with our benzaldehyde. We can't be sure of the secondary peak because we don't have standards so they are just guesses based off the NIST library.

The study (It isn't my idea so don't ask why):

We are running milk permeate that has been dosed with benzaldehyde at a range (0, 20, 40, 60, 80, 100 ppm). These are fine and have no contamination or small enough that it isn't much more than baseline noise.

We are then making a permeate/retentate solution at various ranges 100% ret, 80% ret, etc dosed with 100 ppm of benzaldehyde. As the concentration gets lower there is a stronger signal of benzyl alcohol/4-methylphenol. I was thinking one of our permeate bottles was contaminated but I have no way of checking since we ran out of the permeate we made the solutions with and the concentrations/response we are getting seem VERY large for bacterial contamination.

All solutions were made on the same day.

We are using a QQQ-GCMS which interestingly enough p-cresol/benzyl alcohol (?) and benzaldehyde have similar enough secondary breakdowns to see good peak resolution for both compounds with an MRM method.

Could it be a different compound being created? The identification from NIST gives benzyl alcohol/4-methylphenol when we run these samples on a different GCMS but I haven't used a standard to check (Don't have one)

When we run just the benzaldehyde we see a very small amount of benzyl alcohol that is 10000+ fold smaller than the benzaldehyde peak.

I know it is a lot of info and I'm sure there is something missing that is key to know.

Thank you for all your help!

This might be a bit broad, but has anyone here had experience (whether success or failure) working as a freelance organic chemist? I'm genuinely curious if anyone has started their own independent business in this field and what that journey has been like. I have access to highly affordable lab space, analytical services, solvents, and proper waste disposal, so I’m exploring the possibilities.

I have a hydrogenation reaction running for a diphenylphosphonate ester. Until now the reaction is kind of slow (not complete after 24h) and you maybe see room for improvement.

https://preview.redd.it/y7gor9lh5tfe1.png?width=2162&format=png&auto=webp&s=877b427192992c2daf4e4bbf5fcd455477dbfe53

The reaction is performed in MeOH (not dried, I saw that similar reaction are also performed in water), PtO2 (3mg) with ca. 20 mg of substrate.

Over night I saw full deprotection of one phenyl moiety and only little conversion to the fully deprotected acid. I assumed maybe the reaction is kind of slow, therefore the reaction was heated to 50 degrees Celsius and I also added fresh catalyst. After 1 h I saw significant improvement of turnover. But after 3 h, the turnover was identical to the one after 1h according to lcms. And therefore I assume it was again stalled.

I added than another 20 mg PtO2 (I know a lot) bubbled directly into the solution which brought improvement.

It seemed that I only see additional turnover, when I add fresh catalyst?

Before I started the reaction, I added the substrate and meoh and the catalyst and bubbled the solution with H2 and afterwards added a sept. The reaction was performed under H2 balloon without direct gas infusion for the first 18 h.

I did not vacuum and argon purge, because the catalyst itself contains oxygen. Do you think elemental oxygen could still be of importance for catalyst activity?

PtO2 is not the active species here, but platin black, which is elemental platin with specific surface structure. But these flakes are kind of big in size and are less fine than for example Pd/C which could also be a factor for the reaction speed?

Despite removing oxygen beforehand and maybe using dry solvent another idea of mine would be the addition of acetic acid, but if possible I would like to avoid it, because it is hard to remove and in the next stage introduce an acid sensitive molecule. If the reaction cannot be improved further I was thinking of switching to benzyl which should be easier to remove?

Hey, our lab has been stumped by this paper https://www.researchgate.net/publication/260299634_Selective_alkylation_of_aminophenols
as we are unable to replicate the results, the reductive amination of o-aminophenol with benzaldehyde. A handful of people have given this reaction a shot, and one time we managed to produce a relatively impure sample of N-benzyl o-aminophenol, however further attempts proved to be unfruitful, yielding the schiff base and or benzoxazoles in a revolting tarry product. So far we've tried using air free conditions and harsher conditions for reduction / suppression of quinoid tautomer https://pubs.acs.org/doi/10.1021/jo01360a019 but nothing seems to reliably produce the desired compound. We are entertaining the idea of a buchwald hartwig amination with benzyl bromide, but there is a shortage of good ligands for couplings so... I'd like to ask whether there is any alternative route that y'all know of

Hello everyone! I am looking forward ro run my samples on a GC-FID. Before that, I have the standards' retention time so I know which peaks I should be looking at. The problem is that I have >100 samples and I want to know if there is a way to set up a method that looks for the retentiom times I want and automatically integrates the chromatogram.

Thank you in advance!

Hi all,

Im having issues to remove the byproducts of a deprotection reaction using boron tri bromide. To be more precise, its a benzylated phenol. My product is in the water layer and playing with pH don’t help because it’s a zwiterion. Any tips?

Thanks in advance

Hi, I currently work in a graduate research lab primarily focusing on hydroanimation, hydrophosphorlation, and hydroarsenation. I am mostly concentrationed on the hydroasrenation piece. I just had I question if anyone has an explkaation or a resource into with the DMSO results in a orangish-red color change (from clear) whenever added to the solution. This happens for every different isomer. The original SM are Styrene and Ph2AsH with NaOH; however, once DMSO is added the color rapidily changes. Note this is all done in a glove box, no oxygen. When using the rotovap, a schnek line, and silica based column with hexanes as the ulent, the color completely dissapears. If anyone has an aswers or documentation that could help me figure out this mechanism that would be great thanks.

I am a Medicinal Chemist with 2 years of Postdoc experience. I have 2 patent applications and 5 publications and some pending(Tet Lett, BMCL, J Crystallography etc). I received a job offer, Senior Scientist I at a startup. My boss counter offered with a job in a company he is setting up. He gave a verbal promise to match the pay offered for the Senior Scientist position.

The counter offer is a position in CMC and IND enabling studies. The exact position has not been made clear to me yet but I will be working under a more experienced CMC lead. As the company is being set up I am realizing that my boss is going to be pretty removed from the organization of his new company.

My questions are, how do I negotiate my expected salary with the new boss since I was promised a Senior Scientist salary? Since it is going to be only me and this other CMC lead on the team, can I ask for a higher base salary?

I have CMC experience but it is limited. I am realizing that I really enjoy CMC and managing preclinical work as I am being introduced to it. How do I position myself to be in a managerial/director level position in the near future when I am negotiating an offer?

Any advice would be greatly appreciated!

Recently I’ve been attempting to a Steglich esterification. I’ve gone through numerous protocols as well as discussed with other lab mates what could be going wrong.

I’m using either methacrylic or acrylic acid as the acid reagent and mainly two main alcohols (one is hydrophobic diol and high MW and the other is smaller molecule diol with a urethane group). Both products are commercially available and are low viscosity clear liquids, but when I attempt to synthesize them, each final product is almost like a waxy solid. I’ve checked via FTIR and there are some other peaks that don’t match with the commercial samples. I want to test NMR but our core is backlogged until end of April.

Each attempt I’ve followed this same protocol; into a flask add acid (2.2 equivalents), alcohol (1 equivalent) and DMAP (3mol%) to DCM then place in ice bath. Then add DCC (2 equivalents) in DCM drop wise into the flask. Work up 24 hours later by filtering urea product, washing with aqueous HCl, washing with sodium bicarbonate, washing with aqueous sodium chloride, drying with sodium sulfate. Remove solvent via rotovap.

Has anyone run into something similar or could offer some advice? To add, the point of this synthesis was to recreate a middle product that is more cost effective and greener and I’ve been successful in isolating each of those, but somehow am stuck on something so simple. Any help would be greatly appreciated!

I synthesized PMMA nanocapsules in an acetone-water medium. I have tried all solvents (MeOH, EtOH, IPA, etc.) to precipitate the PMMA, but it is not precipitating.

Any easy cleanup methods for isolating heroin from fentanyl powder drug samples for GC analysis? Ideally while also removing caffeine in the process. Unfortunately, many of the extractions I try to remove fentanyl also remove the heroin.

FYI I’m a forensic chemist needing to certify this compound, preferably without overloading and taking down an instrument in the process.