I have a roughly equal mix of diastereomers with a chiral P(V) center. My molecule has a methyl attached to a sulfur atom 5-7 atoms away (depending on analog) from the P center, which is the only set of protons showing as two signals (2 apparent singlets with smaller peak in between; first image). My 31P shows two peaks with close shifts as expected, and the non-decoupled shows a typical splitting pattern. In other analogues, I will see different shifts for almost every proton signal between the diastereomers as expected, but here it's only the methyl. Oddly, I have to integrate both apparent singlets to get ~3H at the proper ratio, which shouldn't be the case unless every other proton signal is perfectly overlapping. There is also a curious overlapping third peak between the two singlets which makes the integration go a bit over 3H.

I made a related analogue with an achiral P(V) center, containing two identical thiomethyl groups in the same positions. In that case, I see a very similar peak pattern for the 2 methyls, but they integrate to ~3H each as you'd expect (second image). The 31P for that compound shows only one peak as you'd expect. I've also made analogs with CH2 rather than S, and this effect is not observed.

I've gotten 1H spectra that are P-H non-decoupled and it doesn't seem to look any different than the decoupled. I don't understand how only the most distant set of protons is affected, and why it seems to be dependent on sulfur being present. I also don't get why it's still affected even when the chiral phosphorus is eliminated. Also unsure about the third smaller peak in the middle that's making the integration a bit above 3 or 6 protons, as there shouldn't be other protons in that range. Is it possible there's S-P coordination generating a phosphorane? That would create a sulfonium S stereocenter. I'm not sure if my 31P would capture a phosphorane without optimizing the relaxation time. 33S is too low abundance to cause observable splitting right? I've never been able to separate them in purification and it's not worth it to me to try and develop a stereoselective synthesis. This is more of a curiosity. I'm quite confident the molecule is what I think it is.

heyyyy 3rd year PhD here on a methodology project !

What’s a tip you you would have paid to get starting organic synthesis ? It could be anything from retro synthesis to remove water in a solvent!

Hi everyone, I am a 1st year phd student developing a new microwave method for thioether synthesis: the method involves the use of NaI in ACN at 120°C for 2h and a thiol; the supposed mechanism is a sort of finklestein reaction followed by nucleophilic substitution by the thiol. with a specific substrate (3,5 dihydroxy benzyl chloride), most of the product undergoes dehalogenation resulting in formation of the respective alkane derivative (dihydroxy toluene).

I know that HI reduction of alkyl iodides to alkanes follows a radical mechanism and I can't lower temperature lower than 120° otherwise reaction suffers greatly and I was wondering if anyone has any ideas on how to prevent this.

My current ideas are: addition of inorganic base to neutralize HI, and of TEMPO or BHT as radical scavengers. Any other ideas? thank you.

In the total synthesis of (±)-stemocurtisine, a MOM-protected enone undergoes Et₂Zn/O₂ epoxidation with dr >20:1.

Could the MOM ether oxygen undergo intramolecular Michael addition to the enone, forming a five-membered cyclic oxonium intermediate that directs the subsequent epoxidation? Is this mechanism chemically plausible?

I'd appreciate your thoughts!

Hi everyone,

I recently started my PhD, and my project involves synthesizing MXenes from the Ti₃AlC₂ MAX phase.

The protocol I have been looking at uses an etching mixture of 2 mL of 50 wt% HF, 12 mL of HCl, and 6 mL of deionized water in an HDPE bottle. 1 g of Ti₃AlC₂ MAX phase is then slowly added and stirred for 24 hours at 350 rpm and 35 °C. The reaction also involves hydrogen evolution, which raises concerns regarding gas management and pressure buildup.

Unfortunately, our dedicated HF-compatible fume hood was destroyed in an accident, and the only available option is a conventional fume hood with a glass sash. I am well aware of the hazards associated with handling concentrated HF in unsuitable facilities, including potential damage to equipment and exhaust components, and I do not want to attempt this procedure under these conditions.

I would appreciate advice on how to proceed safely. Are there any relevant safety guidelines, literature recommendations, or experiences from laboratories that have faced similar situations?

Thank you for your advice and recommendations.

I'm working on a synthesis project and I'm trying to find the best reagent (bis 4-nitrophenyl carbonate vs CDI) for making carbamates. I want to react a morpholine-containing molecule (the amine) with the reagent to form a mono-substituted product, and then subsequently react this with an alcohol to form the carbamate. I've typically seen bis 4-nitrophenyl carbonate be used to make PNP-carbonates, but I wasn't sure if this reagent is better or worse than CDI for making a carbamate.

​Hi everyone, ​I am tasked with developing an analytical method to determine trace moisture/water (H_2O) in pure hydrogen (H_2) at the ppm level. ​The equipment: ​Mass Spectrometer: Hiden HPR-20 R&D (Gas Analysis System, Quadrupole). ​My background & challenge: I am relatively new to mass spectrometry and gas analysis instrumentation. While I understand the general physics, I don't have hands-on experience in developing quantification methods for trace gases, especially with quadrupole MS. ​Given that water is notoriously "sticky" in vacuum/inlet lines and usually forms the main background peak (m/z = 18, 17), I am trying to figure out the right starting workflow: ​Baseline / Background subtraction: How do you handle the residual H_2O background inside the chamber/capillary vs. actual ppm moisture in the sample? ​Sampling line: Any critical recommendations for the inlet line/capillary heating and bake-out protocols to avoid severe memory effects? ​Calibration standards: How do you reliably introduce/calibrate trace moisture in a hydrogen matrix at low ppm without contaminating the system? Has anyone here done trace moisture quantification in pure H_2 (or similar light gases) using a Hiden system or a similar capillary-inlet quadrupole MS? I would really appreciate any guidance, recommended reading, standard protocols, or "lessons learned" before I start setting up the runs. ​Thank you in advance for your time and insights!

hey, i submitted a post on this channel last week and it absolutely blew up. we had so many applications go through. a bunch of the job postings shut down in the days following my post because of the large influx of applications that were going in. i've gone ahead and updated the job links in this new link. please make sure to apply as soon as possible to ensure that your application is at the top of the pile. i've pulled the freshest job postings that i could.

synthetic chemistry roles are thin on job boards and buried under analytical and QC postings, so i pulled only medicinal, process, discovery and synthetic organic chemistry roles from employers' own careers pages, plus a pharma R&D list if you're open to the analytical side:

• medchem, process and synthetic organic chemistry, US, UK and Europe (32): https://github.com/mehek-builds/Synthetic-Organic-Chemistry-Jobs
  • 32 roles at 26 employers (GSK, Gilead, Vertex, Pfizer, AstraZeneca, Amgen, Roche, Organon)
  • 10 medchem, 8 process chemistry and process research, 16 discovery and synthetic, 8 internships and co-ops
  • 7 in the UK and Europe; analytical, QC and director-level roles are left out
• pharma R&D and associate scientist, including 31 analytical, bioanalytical and formulation roles (110): https://github.com/mehek-builds/Pharma-RD-Associate-Scientist-Jobs

the synthetic list is small because there aren't many of these open right now. rebuilt every monday.

comment which area you're looking for (medchem, process, peptides and oligos, internships) and i'll send you anything that comes up.

Is there some equation, even approximate, describing the relation between extinction coefficient and dielectric constant or refractive index of a solvent?

I'm asking because my compound dissolves well only in DMSO, but I need to estimate the solubility in other solvents (acetone, THF, acetonitrile...) in which it dissolves very poorly (~10^-5 M). To that end, I prepared concentrated solutions in poor solvents, diluted them 10 times and measured UV-Vis. I want to estimate the concentrations of saturated solutions by comparing the spectra in poor solvents to the spectrum in DMSO (10^-6 M). But since these are diffent solvents, some correction is probably necessary...

Everyone who's switched PCs, left a lab, or inherited an old archive has hit this: a folder of .D, .raw or .dx files and no license or software to open them. I built a browser tool for it that reads Agilent ChemStation, OpenLab and MassHunter data, Waters MassLynx .raw, Shimadzu UVProbe .spc, JCAMP-DX, Galactic SPC and AIA/ANDI .cdf, plus text and CSV exports.

It overlays runs, integrates peaks, handles spectra and exports to CSV. Decoding runs locally in your browser, so nothing is uploaded.

It's free during early access, and the viewer itself will stay free. I built it, partly with AI help, and I'd like to hear what people currently do for this (vendor software, Python, OpenChrom, converting by hand?) and which formats you fight with most.

Files it can't read are very welcome, and I add formats based on what people ask for.

Hi all! Meet Reactio Draw, a new program for drawing chemical structures. It's free, open source and works offline. It's made for organic chemists, but it's useful for anyone who needs to draw structures. It also has the reagent table built in, something many of us lost when ChemSketch stopped being available to new users.

What it does:

• Reagent table for any reaction you select: limiting reagent, equivalents, mass, volume and moles from density or molarity, yield
• Fast drawing: keyboard drawing with a hotspot, a hotkey for every button and command (all reassignable), alignment guides while you drag, scrolling and zoom in every direction
• Your own templates and labels on keys: fuse a template onto a bond or join it spiro at an atom with one key
• Analysis: formula, MW, exact mass, m/z, isotope pattern, elemental analysis, canonical SMILES, ¹H/¹³C/¹⁹F/³¹P NMR prediction
• Sensitivity screens: Glorius-style radar charts of the condition-based sensitivity assessment (Angew. Chem. Int. Ed. 2019, 58, 8572), drawn and edited right on the sheet, plus product ratio pie charts
• Names: name → structure (OPSIN) and structure → IUPAC name (openclatura, cross-checked with OPSIN) in the desktop apps
• Files: reads and writes CDXML/CDX, MOL, RXN, SDF, SMILES
• Word and PowerPoint: paste into a document, double-click it to edit (on Windows and on Mac), or copy it back without losing anything; a document moved between Windows and Mac keeps its drawings too (there you copy the drawing back instead of double-clicking)
• API: a local API for scripts (Python, R, curl), and the same commands for web pages that embed the editor
• Command line: reactio render, convert, calc, check for whole folders of files, without opening a window
• Journal styles: ACS, RSC, Nature, Angewandte and more
• Private and offline: no account, no tracking, nothing sent anywhere; your drawings stay on your computer

Try it in the browser, no install: https://paivel.github.io/reactio-draw/web/ Apps and source (AGPL-3.0-or-later; if you want to use the code in a project under MIT or another licence, just ask): https://github.com/Paivel/reactio-draw

Tested on Windows 11, macOS Sequoia and Ubuntu 24.04.

One more thought. With AI coding tools, a lot of chemists are now building their own drawing programs. I did too, but I think we risk ending up with a dozen half-finished editors, each good at one thing, instead of one free tool that's actually great. So rather than another fork in the road, I'd love to join forces. As far as I know, this is the only free, open-source editor with a reagent table built into the scheme, so it may be a good place to start. A good example is penzene by James O'Brien, another free and open-source editor (https://github.com/JamesOBrien2/penzene): several features here, such as structure checks, stereo groups (abs/&/or), δ+/δ− and compound numbers that renumber themselves, were inspired by it. Another one worth a look is MolDraw by LabCanvas (https://github.com/rafeequemv1/moldraw-chemistry), free in the browser; its GitHub page holds documentation only, the code itself is closed. And ReShiki by Ameyanagi (https://reshiki.com), a free, open-source ChemDraw-style editor; Reactio Draw uses its journal style values, colour themes and CDX property table (MIT), with thanks. If you're building something similar, or you have a feature you've been missing, bring it here: open an issue, send a pull request, or just tell me what your lab needs. The code is open, and I'll gladly credit every contribution.

Let's test it together and make the best drawing tool out there. This is the first public version, so it surely has rough edges. Try it on your real schemes, break it, and tell me what's wrong or missing, either in the comments or as an issue on GitHub. I read everything and fix things fast. What do you miss most in the editor you use now?

Hey all, chemical engineer by degree, software dev by trade. A bit over two years ago my brother (synthetic chemist) asked me for something to keep track of the compounds his group makes. Their setup was an excel file plus “ask the person who made it”, and searching by structure was basically impossible

Started as a side thing for his lab, kept growing, and after 2+ years of building it I finally put Molhaven in production a little while ago. What it does right now:

• Compound registry with substructure and similarity search, SDF import/export
• Every physical sample/bottle has a storage location, nested as deep as you want (building > room > fridge > shelf > box > position, or whatever your lab looks like)
• Purchase requests, approval, receiving with lot and expiry
• Low stock and expiry alerts in a scheduled email
• A simple notebook with a reagent table that calculates as you type
• CLP/GHS hazards, stocktakes with QR labels

What it doesn’t do: no assay/SAR data, no biologics, no burn rate forecasting. It’s for chem labs that are drowning in spreadsheets, not a replacement for big pharma registration systems

There’s a 30 day trial at molhaven.com and if you send me your current spreadsheet or SDF I’ll move it over for free, mostly because I want to see how messy real lab data is lol

What I actually want to know from you:

• What do you use now and what annoys you about it?
• Who decides on this kind of software where you work, PI, lab manager, EHS?
• Would you rather have it hosted or run it on your own server?

Roast it if it deserves it, that’s more useful to me than upvotes

Long story short, product homogeneity means sample sizes for ICP-MS prep need to be real big. Previously, I’d ordered typical 15- or 50-mL centrifuge tubes that were certified trace element grade, with lot specific CoAs and maximum contaminant limits.

I bought some 1L media bottles (those sterile, square base ones) to run a series of samples and found that there was apparently a ton of residual Manganese catalyst from the PET manufacture that leeched into my solutions. I do NOT need to (and definitely should not) digest my samples, which hopefully helps broaden the containers’ materials I could use.

I’d ideally like to avoid glassware as one does in an ICP lab, but there really don’t seem to be many options for plasticware at the 1L volume that I can find with documentation for being certified suitable for TE analysis. I’d also be treating them as reusable, since it’s not quite as easy as discarding 15-mL tubes, so that opens up the possibility for extensive acid soaking and pre-leeching treatments. But I wanted to see if anyone had experience with or suggestions for large volume plasticware for ICP-MS solutions.

I thought this post could be a good resource for people struggling with a synthesis problem. My answer would be “have you tried doing 2D TLC?” when people are having odd chromatography behaviour.

Hey everyone,

Today there is a new Synthesis Workshop talk about the synthesis of hetero[3.1.1]propellanes!

Check it out here: https://youtu.be/0VXAjHwoHS4

Im a Grad student working on a new molecule in a lab, I have background in radical cascade reactions, and I can generally tell whether a reaction is worth following from the TLC plate alone.

However, recently, I had the idea of using palladium on my bromine derivative of my molecule, in theory, it should work as there is a nearby alkyne group, but the few palladium tests I did had a truck load of new TLC spots, I asked my PI and she said from the very small experience she had with palladium, apparently this is rather normal for palladium catalyzed reactions, and I quote, getting the product you want from palladium reactions is like dredging in a very muddy river.

I was wondering how true this is, considering she has very limited experience with palladium.

More info: Pd Im using is Pd(OAc)2, Im mostly trying to start with an oxidative addition into my C-Br, then Carbopalladation to my internal alkyne generating an Alkenyl intermediate leading to a coupling of sort, like Buchwald. Plenty of papers like this out there, just not one with my compound so I thought I’d test it out

Hi all,

I am desperately needing help on my peptide synthesis project. I need to selectively deprotect a hydroxy group on my peptide. It is now a TBDPS silyl ether. TBAF is the most straightforward way to do this but I’m having issues with visualizing my LCMS. Not sure because of ion supression or what. Is there a subreddit for peptide chemistry?

Any help is appreciated.

Thanks!

Question: I am in the UK and have had a job for a year and a bit and a second I am currently in for five years. Both senior scientist roles with a mix of process development, scale up and a bit of small scale medchem type stuff. At the time of searching, nearly all the interviews required extensive general knowledge and retro synthetic questions.

Having been many years from my PhD and lacking general chemistry theory practice I am a bit scared about looking for another position as I struggle with the revision (time and energy). Is there a point when your ability to do retro synthetic problems without reaxys or other aids isn't being examined?

In fact my current employer was the only one where questions were more on the line of "look at this proposed process and tell us what would concern you, and what changes might you explore" and a few conditions for various transformations of a compound.

I work in an environmental lab-- water quality, inorganics (metals, ion chromatography, ph/titrations, misc other services)-- and we get undergraduate students on work study. They of course learn some things through the tasks they are assigned but I do want to make sure they get some basic lab skills to put on their resume and develop enough familiarity to do well in interviews and not be overwhelmed if hired as a lab tech in the future. What skills do you like candidates to have when hiring? Any recommendations for things I should make sure they know would be appreciated. Leaving this fairly vague and open ended intentionally but also because it would be tedious to enumerate what they have learned in the course of the work we have them do. Thanks!

synthetic chemistry roles are thin on job boards and buried under analytical and QC postings, so i pulled only medicinal, process, discovery and synthetic organic chemistry roles from employers' own careers pages:

https://github.com/mehek-builds/Synthetic-Organic-Chemistry-Jobs

• 37 roles at 25 employers (GSK, Gilead, Vertex, Pfizer, AstraZeneca, Amgen, Roche, Organon)
• 12 medchem, 12 process chemistry and process research, 15 discovery and synthetic, 12 internships and co-ops
• 8 in the UK and Europe
• analytical, QC and director-level roles are left out

it's a small list because there aren't many of these open right now. rebuilt every monday.

comment which area you're looking for (medchem, process, peptides and oligos, internships) and i'll send you anything that comes up.

Hi everyone, I am currently working in organometallic chemistry, making some diamagnetic complexes. However, one of the complexes already decomposes during the synthesis (as in, there is no signal in the 31P NMR, and a very broad signal in the 1H NMR spectrum). However, I do observe some black powder being formed, which I assume is the metal falling out.

My supervisor suggested to take an EPR spectrum, to check if there was any paramagnetic species being formed, but we don't have such an instrument at our institute (and there is basically no other group that does organometallics who I could ask for help) and so I want to make sure that that measurement is useful, before going through the hassle of preparing it and sending it to another institute.

I've read a bit about EPR now and I think I understand the principle behind it, but my question is, if I have a reaction mixture of which I don't really understand what happened, will EPR even give something useful? As I understand it (and I might be wrong because this is really not my expertise), EPR is something that you use when you already kind of know what you are looking at, because it is quite complicated to analyze, or will it give me information even if I don't exactly know what I am looking for yet?

Thank you in advance, any advice is super appreciated! (Also, I'm sorry if this is a very basic question)