Category: Graduate School

• A wide-bore needle is great for dipping TLC capillaries into airfree reactions. Try at 15 or 16 Ga. needle for commercial tubes (18 Ga. works if you order thin capillaries or pull your own, e.g., from Pasteur pipettes).
• Handy flash chromatography tricks
  • This is based on a post from Phil Baran’s excellent blog. For small reactions (50–150 mg), 160 mm test tubes are convenient, disposable columns for flash chromatography. They are also highly useful for ion exchange chromatography, etc. Simply use a Bunsen burner and forceps to make a hole in the bottom, jam a cotton wad in, add a thin layer of sand, and pour in your silica gel/stationary phase (leaving plenty of room for mobile phase at the top). Apply pressure with a standard 14/20 gas adapter.
  • Pipette columns are highly convenient for purifying 10–40 mg of material, as noted by Alison Frontier’s excellent “Not Voodoo” page about it. I have a few practical tips to add for running these columns (see picture):
    • 1/2 dram glass vials are convenient for collecting fractions, and can easily be organized in a Simport Scientific “UniRack Jr.” rack (Fisher 22-038-542, Simport S50025Y). The pipette can be left standing in these vials and positive pressure applied as needed via Tygon tubing.
    • To “pause” the column, plug the top with a small septum (a 5 mm ID x 11 mm OD/ 8-9 mm OD tubing VWR sleeve stopper is shown here, VWR cat. no. 89097-534). After the stopper pushes out a few drops of mobile phase, flow will stop if you’ve sealed the headspace properly.
    • Set the R_f to 0.2, or set it to 0.3 and then either 1) cut the %EtOAc in half, or 2) switch EtOAc to Et₂O (which has half of the eluting strength).
  • For purifying polar compounds, there is no reason to shy away from highly polar mobile phases. There’s a common myth going around that silica gel dissolves in mobile phases containing a high percentage of methanol. Newsflash(chromatography) — this has been disproved time and time again ([1] [2]).   I routinely use the following mobile phases and have never had a problem:
    • Amino acids with less polar side chains: 50:50 dichloromethane:methanol
    • Gangliosides: 60:35:8 chloroform:methanol:water
    • I have even filtered an aqueous solution of an amino acid over silica gel. For that, I did use a syringe filter to remove particles.
    • For TLC, there are no limits! 3:1:1 n-butanol:water:acetic acid, for example, is great for amino acids. It is quite viscous and runs slowly, however, and would be poorly suited for flash chromatography.
  • For sensitive compounds (e.g., electrophiles), consider using specialty deactivated silica gel (post forthcoming).
  • Reference: the original flash chromatography paper is only < 3 pg. and worth a read. Read for free at https://tinyurl.com/uzlcl6z.

LabArchives—love it or hate it, a growing number of academic institutions are adopting it (reviewed here). As a “jack-of-all-trades” electronic lab notebook, it tries to cater to every field of science. If you do organic synthesis research, you may be disappointed at first as you struggle with the silly chemical sketcher widget, complete lack of integration with ChemDraw, and weak stock spreadsheet widget. Once you learn to use it, however, LabArchives isn’t half-bad. While it may not offer all of the chemistry-specific bells and whistles that come with Perkin-Elmer’s offerings or the slick ease-of-use that comes with (more biology-focused) Benchling, LabArchives is a serviceable option for synthetic chemists with the right tricks.

A good notebook entry for a reaction consists of three parts:

1. Structure drawing,
2. Table of reactants, and
3. Experimental write-up and characterization data.

Here’s how to tackle all 3:

1. Structure drawing

1. Just make it in ChemDraw!
2. From there, copy and paste the structures and arrow into a Word document.
3. Copy and paste from the Word document into a rich text entry in LabArchives.
4. In ChemDraw, select the product, and use the Structure → Convert Structure to Name command (⌥⌘N (Mac) or Ctrl + Alt + N (Windows)). Double-click it to resize.
5. Then, use View → Show Analysis Window → Paste to add formula, molecular weight, and exact mass to the document.
6. Copy the text box near the structure containing the IUPAC name, formula, MW, and exact mass, and paste into the LabArchives rich text entry.
7. (Optional, but makes searching easier) Copy the structure as a SMILES string (Edit → Copy As → SMILES (⌥⌘C (Mac) or Ctrl + Alt + C (Windows)), and paste.

2. Table of reactants

1. Create a Google sheet.
2. Starting in cell B7, make columns for the following:
   1. Compound
   2. Abbrev.
   3. Amount
   4. Unit (narrow column—just big enough to fit “mg” or “µL”)
   5. mmol
   6. MW (g/mol)
   7. d (g/mL)
   8. (Optional) CAS
   9. (Optional) Source
3. Use formulas to make all of the calculations (e.g, for mmoles, just do =[amount]*[density]/[MW]). I like to calculate the theoretical amounts of all solids I’m supposed to weigh out, then go back and fill in the actual amounts as I weight them.
4. Press “Share” in the upper right. Change the sharing settings to “Anyone with the link can edit,” then copy the link.
5. In LabArchives, insert a Google Doc and paste the link. When you hit “save to page,” you’ll have a decent spreadsheet you can edit in your notebook.

Bam!

3. Text and characterization data

1. Write up an experimental.
   

   Acetic anhydride (150. µL, 1.59 mmol, 2.2 eq) was added to a solution of salicylic acid (100.3 mg, 726.2 µmol) in anhydrous pyridine (2.5 mL). The reaction mixture was stirred for 10 h at ambient temperature. It was diluted with 0.1 N HCl (20 mL) and extracted with EtOAc (3 x 15 mL). The pooled organic phase was dried (Na2SO4), filtered, and concentrated in vacuo, affording acetylsalicylic acid as a white solid in 87% yield (113.8 mg, 631.8 µmol).

2. Upload all relevant data (I do PDFs exported from TopSpin for NMR). FolderMonitor could be good here (if you install it on the computer where you collect a lot of data and set it up to upload it automatically), but I find it’s easier to just upload to each individual page.
3. For TLC plates, take a photograph of the plate with your phone. For UV-absorbing compounds, I like to cut a ~1″ square hole in the top of a shoebox-sized box, cut a ~3″ x 6″ “door” in the side to shine in a UV lamp, and then photograph the plate inside the box. My photos automatically upload to Google Photos. Then, I quickly crop the images in Google Photos, right-click and copy them, and paste them into my notebook entries (the rich text portion). I double-click them to resize them to something reasonable (e.g., 300 pixels in height).

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Organization

I prefer to put each compound on its own page and number each page. Every now and then, I get characterization data for reagents, which I put into a “Reagents” folder.

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Conclusion

LabArchives is a versatile platform for lab notebooks. It can be useful for synthetic organic chemistry if you make the proper tweaks and take advantage of other applications’ functionality (e.g., ChemDraw, Google Sheets, and Google Photos) to make it work.

Intro rant:

Whether you like it or not, many researchers are switching to electronic lab notebooks. LabArchives has arisen as a popular choice. A growing list of universities and research institutes have contracts with LabArchives, so several thousand researchers now use the platform:

As one of the older/larger ELN companies, LabArchives is unlikely to go under. That said, the “jack of all trades, master of none” trope certainly describes LabArchives. It’s a versatile platform that can handle many file formats and works okay for research in many different fields. It comes with many widgets that offer half-baked support for key tasks in the field. For example, in my own field of chemistry, it offers a “Chemical Sketcher” widget based on ChemDoodle. It has all of the basic functionalities you’d want… except for integration with the software nearly every chemist actually uses for this purpose (ChemDraw)! It doesn’t even recognize SMILES structures copied from ChemDraw with its so-called SMILES search when searching through these (nearly useless) chemical sketcher entries. Consequently, there is little reason to use widgets like these. I imagine that researchers in other fields have noted similar limitations.

The general-purpose widgets are similarly disappointing. For example, the spreadsheets widget doesn’t integrate with Excel, and is riddled with bugs that make it nearly unusable for even the simplest tasks.

Lastly, the smartphone app (at least on Android phones) is a joke. It can’t display images and locks up all the time. It’s barely functional. It’s been this way for years, and my impression is that the developers simply don’t care. The company probably just wants to tick the box of offering a smartphone app.

Interestingly, the website gives falsely elevated numbers for the reviews. I checked the Google Play store on my Android and had my friend check the app store on his iPhone to get the real story:

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Pros and Cons (vs. paper):

Pros:

• Searchable (but you have to be careful to paste in SMILES strings or other useful chemical information if you want to have anything approximating a structure search).
• The ability to copy and paste is huge (but watch out for “copy forward errors” where you forget to update something!).
• There’s need to lend someone your notebook for them to have a look.
• The data is off-site so a disaster in your building will not destroy it.
• It’s easy to track revision histories for intellectual property claims.
• Everything you need (e.g., experimental procedures, NMR spectra, MS data) is in one place.
• Accessible from home, the coffee shop, etc.
• Can link to electronic versions of literature articles.
• Good integration with Excel (automatically updates) and with GraphPad Prism.
• “FolderMonitor” can automatically upload data from a computer (e.g., NMR spectra) as soon as they are generated, providing a convenient off-site backup service and helping to keep all of your data together. In practice, however, the app doesn’t always work.

Cons:

• It’s a huge pain in the ass to move items around on a page if you have 3 or more. It takes forever—drag and drop would be great here.
• It’s harder to make sketches electronically; photographing paper sketches is generally easier.
• Clumsy interface for updating files (should just be drag-and-drop with automatic updating and version history like Google Drive if feasible).
• Cross-linking pages in notebook can take a while to navigate in their tiny interface for it, particularly once a notebook has a lot of entries. Also, it displays a really small link that’s tough to notice unless you’re specifically looking for it.
• Fundamentally less portable to the bench unless you have a dedicated computer.
• There’s no good way to keep track of a lot of images. You can upload them all and see individual thumbnails, or can paste them in rich text entries, but you have to double-click them and type in dimensions to resize them, and you have very little control over their positioning. Implementing something like Google Photos or Flickr would be good for keeping track of multiple images.
• Switching platforms is nearly impossible once you get going with one.
• (Very rare): You may not have access due to network problems. In my experience, these are usually my university’s fault and not LabArchives’s, however, and LA does a good job of minimizing interruptions due to system updates (they are usually at 1 AM on Saturday nights if memory serves).

In my field, it’s possible to cobble together a decent notebook entry for organic synthesis experiments. My next post will explain how to do just that.