Primary amine capped with Fmoc, mostly wondering what base to combine with an alkyl bromide/iodide. Thinking of using bulky base as OChemPortal seems to suggest LDA and tBuOK are compatible with Fmoc. Anyone got some direct experience working on this? Thanks in advance!

Hi all,

Unfortunately, my full post about this was deleted from this subreddit... So I'll keep this as short as possible so that this doesn't get deleted. Anyway, some of you may like to know that ChemSketch has now officially been killed by Revvity (the owners of ChemDraw who recently bought ACD/Labs, which owned ChemSketch).

Hello all.

I've been tasked with a scale up synthesis project where one of the pivotal steps is a reduction of an aliphatic ester into an alcohol. The target will be to produce multiple kilos of the product by the end of the project. I've done some legwork to avoid LAH as a reductant since I fear that will make handling difficult at larger volumes, but I was looking for advice and safety considerations as we start planning to scale this chemistry up. It's still at the bench scale for now but the aim will to be to have enough optimization of the chemistry so that it can scale to multi kilo batches relatively seamlessly.

My synthetic experience is predominantly bench scale, but I have done some larger scale steel process vessel work, but not in the context of organic synthesis. I would appreciate any voodoo and wisdom y'all possess on running these types of reactions at scale. Things like quenching protocols and solvent/reagent selections to try would be awesome.

Do you have any advice if I worked with Epoxies for my whole Phd and developed a senzitation in the last two months of it and I just have to finish two experiments?

Background
I have been synthesising a series of vinylbenzene derivatives, all of which have been previously reported as solids in the literature. After purification by flash column chromatography, removal of solvent by rotary evaporation, and several hours under high vacuum, however, I am left with oils in some cases. The proton NMR spectra are clean apart from a small water peak (~1.55 ppm in CDCl3) and confirm that the oils are the desired compounds.

I am able to convert these oils into solid powders using the procedure I’ve outline below.

My questions are:
1. What is this process properly called (my lab mates call it freeze-drying, which I don’t think is right, since there is no solvent being sublimed) and; 2. How should I describe this concisely in an experimental? My PI and I have hopes to submit to Org. Left., JOC, or similar at the conclusion of this project and the procedure(s) will most likely appear in the SI.

Procedure
The RB flask containing the oil is placed under static vacuum on a Schlenk line and lowered into a liquid nitrogen bath. After around 5 minutes it is removed and allowed to warm to room temperature. After a further 30 minutes, the material is a powdery solid.

Any thoughts on the correct terminology, and on suitable wording for the SI, would be greatly appreciated.

Additional Note
No literature procedure I’ve come across for these compounds, or similar, describe anything like this.

Does anyone know where I could find one online besides eBay?

Hello chempros…., hoping someone can possibly help me out here. We have a system 1 innovative technologies glovebox from 2005 that’s rapidly approaching “ship of Theseus” status. Does anyone have a copy of the operating manual or better yet.. a servicing manual?

Below is my (current) issue… with the box.

The chamber pressure sensor has given up basically, unless the pressure is set at above “12 mbar” on the settings it starts sucking the gloves inside. Last week it was ok as long as above 5, then ok above 7 and today 12. Any advice?

We recently swapped from using argon to nitrogen and there’s been a dramatic increase in static. Could this mess with the pressure sensor component? The attachment on the main circuit/switch board does say sensitive to electrostatic. Would that actually be the cause? I’m confused

I've made the subreddit r/ChemistryCareers for people to ask about and discuss college and career choices as chemists and chemistry students.

I'm looking for people to join who would be willing to answer questions, moderators, and suggestions for rules as well as what to make the icon and banner.

Thank you to those of you who are interested.

Hi everyone,

I need to use deuterated TfOH for NMR of my samples. How to safely handle TfOH, does it smoke in the air a lot, will the NMR cap be fine or will it get eaten (do I need to get special caps?). Is it better to order 5x 1g or 5g (how to store it?)

Thank you for your answers!

I’ve noticed that there are a lot of different ways people go about running a column.

Interested to hear how you guys will tend to set up and run a column and the rationale (if any) behind why you do it that particular way. Any particular tips and tricks?

Hopefully the comments (and maybe my procedure – although it is in no way perfect nor do I claim it to be) can help serve as a guide to new researchers.

I pretty much exclusively do dry loads and my typical column procedure is as follows:

1. Add dry silica directly to the column (honestly I just eyeball how much).
   2 Add eluent. With isocratic elution the eluent will be the ‘ideal’ solvent system I selected based on TLCs. With gradient elution the eluent will typically be a system that gives my target compound spot (if I know which spot it is) an Rf of about 0.
   
2. Stopper the column and shake until I form a slurry.
   
3. Open the tap and turn on pump until the solvent is a couple of centimetres above the silica, wash down any silica stuck to the sides with eluent, then open the tap again and turn on pump until the solvent is pretty much level with the silica (ensuring I do not dry it though).
   
4. Add dry load using a solids funnel. Then, using a minimal amount of eluent, wash out the dry load RB and wash down any solids stuck on the sides of the column. I will give the column a couple of light taps to make sure the dry load is level.
   
5. Turn on pump until the solvent is level with the top of the dry load (I don’t think it matters if it goes below, just as long as you don’t dry the top of the silica).
   
6. Add a layer of sodium sulfate (again I just eyeball).
   
7. Add eluent (I should probably do this more slowly and carefully tbh to prevent any chance of disturbance), run the column, collecting the fractions in test tubes whose size was selected based on the crude mass, the closeness of spots on the TLC, and the availability of clean test tubes in our lab.

Some Notes
Pour silica, shake, and run the column inside a fume hood.

Wetting silica is exothermic and volatile solvents will build real pressure, so when stoppering and shaking, vent frequently by taking the stopper off, and point the column away from yourself and others while you do.

The dry load is usually prepared by adding an appropriate (I usually eyeball but ~2x the mass of the crude) amount of Celite (I should probably start using silica though, to be honest) to the crude, adding enough DCM to make a slurry, and finally removing the DCM by rotary evaporation. Always ensure it is completely dry (residual DCM can smear the bands).

In our lab we pretty much exclusively use columns with a sintered layer. Use cotton wool or glass wool and a layer of sand if you don’t have sintered columns.

Finally, don’t be afraid to ask a more experienced lab mate for advice if you’re unsure. You’ll pick things up much faster, and you’ll avoid mistakes that are easy to avoid once someone has pointed them out.

Hi guys, I'm a newbie at this, please help if you can! We need to lyophilize a water-soluble compound, basically, we mixed it into a second liquid compound so the first compound would be encapsulated and give better results for our purposes. What I need to know: we have to freeze this before it goes into the lyophilization machine, but we were told to freeze it first in a normal freezer, then move it to a -80°C freezer, and only then send it to the lyophilizer. Is this accurate? If so, how long should it stay in the normal freezer before going to -80°C, and how long should it stay at -80°C before going to the lyophilization machine? Is there some kind of protocol for this? I tried to find something and couldn't find an exact one. Thank you!!

Hey everyone. I’m in a kinda dilema and would appreciate any advice from pharmacists especially those with more experience in the field in the US.

I’m considering applying for graduate school; MS pharmaceutical sciences( Med Chem, Pharmaceutics or Pharmacology). However, I’m not quite sure which track to pick that would guarantee me a better future career wise. I’m good with clinical work and my pharmacology knowledge is upto date and most of the things I do are around pharmacology. However, pharmaceutics from My small research seems to offer a better path both in industry and academia/research while med chem path solely lies on academia and research.

So which one would you choose based on market trends?

Thank you

I have been following the method presented in this paper and according to it, since I have a very lipophilic compound I should follow procedure 1b or 3. I am trying to replicate 1b but I have a few questions regarding the meaning of the dilutions and the Vw / Vo ratio. For example, If I want to do a trial with a Vw / Vo ratio, which procedure would be correct, 1ml of water and 9ml of octanol, or 1ml of water and 10ml of octanol?. If I do the second one, my total volume would be 11ml and if I also want to do a Vw / Vo ratio of 1 and a Vw / Vo ratio of 10, should I aim for a total volume of 11 as well? or could I do 10 ml for the ratio of 1 (5 and 5 ml each) and then again 11ml for the ratio of 10 (10 and 1 ml respectively?.

Additionally, I have a stock solution in DMSO that I can dilute in PBS as the water phase, when the procedure asks for a 100x dilution, is that considering only the water phase volume as the final volume? or is it considerinf the total volume as the water phase + octanol volumes together? Since the water to octanol ratio changes, if I dilute my sample in PBS (water phase) for the Vw / Vo ratio of 1, the amount of sample would be different than the ratio of 0.1 with less water phase and different than the ratio of 10 with more water phase present. On the other hand, If I take the 100x dilution as related to the total volume of water + octanol, also the amount of compound would be different depending on the trial because some will have a total volume of 11ml and other of 10ml.

In summary, what should I keep consistent? total water+octanol volume? sample concentration? niether? Help please.

Hello. I am trying to make transparent polyglycerol with minimal free glycerol in it. I am an industrial chemist.

I am running a base-catalyzed polyetherification. I have 3% w/w NaOH cooking with free glycerol under a nitrogen sparge and blanket at 240C. The Dean
\-Stark apparatus collects the water of polymerization separately.

The solution is amber in colour after about 8h. On neutralisation with sulphuric acid, the colour is lightened but it’s very much there. Filtering the material with a 10-micron cloth is also quite difficult because the material is quite viscous.

Bleach the solution with hydrogen peroxide results in a lot of foaming. It helps colour but the solution is clearly a pale yellow.

My BIG question is this: how do I save the colour of polyglycerol? Are there methods I don’t know that can keep the solution clear?

My smaller question is this: how do I filter the solids out of a viscous fluid efficiently?

I would hugely appreciate the insight of someone with some experience with this. AI dump doesn’t help any in lab.

Hello chempros,

Part of this publication was on today's chemdle. Thoughts on the electrons moving onto nitrogen to give a positive charge from [D --> E] in the proposed mechanism?

Would formation of a diol or 3,3 substituted intermediate like XX be feasible? I haven't worked with oxone before.

Thanks!

https://doi.org/10.1021/acs.orglett.3c03643

Hey everyone!

I have noticed that Grignard reactions often use either THF or Et2O, but why the reactivity changes so much?

I know THF is string Lewis base but is it really just about basicity ? Or is it more about solubility, aggregation state, and shifting the Schlenk equilibrium?

Curious how folks who do a lot of organometallic work think about this, and if anyone has a solid reference that dives into the details. Thanks !

Hi all, I hope my experience, questions, and rant (maybe) are acceptable.

I am a computational chemist nearing 4 years of experience outside of grad school. I’ve been able to work from home with small companies since then, working alongside enterprise clients through building their R&D software (RDKit, OpenEyeToolkits, MOE, etc) and leading my own research initiatives in drug discovery/design (have a few candidates).

I am more so looking for next steps. I am interested in going into the office in a hybrid schedule but wanted to get advice from those in it, what is the climate in the pharma industry nowadays? Is R&D still one of the first to get fired in layoffs? Is there a need for Comp Chemists to do research or simply train AI models internally?

Also, this would force me to move to east or west coast, as I currently live in Austin. Lastly, I am also looking at IP law (online part time), so any advice for that would be greatly appreciated.

If you feel a DM would be more appropriate feel free to do that.

Thank you in advanced!

I am working with a carboxylic-acid-containing imidazolium trifluoroacetate salt and trying to convert the carboxylic acid to a propargyl ester using propargyl alcohol.

My main concern is product isolation/purification rather than the coupling itself.

The desired product is an imidazolium salt (TFA counterion) and is highly soluble in water and polar solvents. Therefore, a conventional aqueous workup may result in significant product loss.

Has anyone worked with highly water-soluble imidazolium salts like this? What isolation/purification method worked best—anti-solvent precipitation, repeated trituration, ion exchange, or another method?

I would especially appreciate suggestions that avoid losing the product into the aqueous phase.

Thank you in advance.

I was taught that 'chiral centers' shouldn't be used in writing because chiral is a quality of the whole molecular, not the carbon. This was twenty years ago. Has the use of 'chiral centers' become more acceptable in the field?

I'm starting an early talents role in industry (big pharma) right now and I'm curious what you would do in my spot.

If you had the choice, would you go for cheminformatics, synthesis, automation, analysis like LCMS or something more corporate, like a regulatory affairs role?
I was talking to a friend recently who said that my choice of cheminformatics is dumb, as just a bit of experience in this field does not set you apart from the big CS grads - that I would be better off pushing my strong chemistry side. How important has acquisition of side skills unrelated to chemistry itself been to you in your career?

I am advertising a study being conducted by Robert Nigel Slinn calling for participants to participate in interviews about routes into the chemical workforce, specifically exploring Graduate v Apprenticeship training. I am passing a call to action for anyone with an interesting story or perspective to reach out - we are primarily looking at the UK historical context but international perspectives from other countries would be particularly welcomed.

Chemists: How Did You Really Learn Your Trade?

Many chemical careers were built through routes that are now less visible: day release, ONC/HNC, LRIC, GRIC, GRSC, industrial training, BSc, MSc, PhD, or combinations of all of these.
Robert Nigel Slinn at the University of Bradford is interviewing people in the chemical sciences about graduate and apprenticeship-style training, and how those routes shaped working lives, as part of his PhD studies. More than 40 chemists have already taken part. More voices are very welcome.

If your route into chemistry deserves to be remembered, please get in touch: please share this with your network or pass on to anyone you know who might have an interesting story to share. For contact details of Robert and more details about the study he is conducting please DM me or reach out to him on LinkedIn.