Vacuum Pumps 101

May I present to you the humble vacuum pump:

Credit: Ideal Vacuum

Credit: Ideal Vacuum

We chemists tend to not give them much thought, which is a shame seeing in that we work with them daily.  Much of our work depends on being able to lower the pressure of a system for whatever reason.  Want to evaporate solvent?  Your membrane diaphragm pump has your back.  Want to distill an irritatingly high-boiling off-yellow mixture to your pristine colorless product?  Look no further than your trusty rotary vane pump.  Need to shoot your compound onto a mass spec?  The instrument’s turbo pump creates the ultra high vacuum environment required for accurate analysis.

I could go on.

Despite the ubiquity and utility of vacuum pumps in the chemistry lab, the trend I’ve noticed is that most workaday chemists know little to nothing about how they work and how to take care of them.

[Screaming Internally]

“Steve, this says the last time you changed the pump oil was April 2014.”

As a result of this ignorance around pumps, I propose all chemistry degree programs, at both the graduate and undergraduate levels, teach a mandatory class on vacuum pumps.  I submit for your review a syllabus outline for this class:

Vacuum Pumps 101

  1. Introduction to vacuum pump types: How to tell a rotary vane from a diaphragm pump
  2. When to use a vapor trap: Always
  3. Oil changes: Coors Lite = good, Guinness = bad
  4. Handling acid vapors: How to destroy a pump
  5. Quiz: What is that sound?
  6. Gas ballast use: Why is my pump oil in two phases?
  7. Lab practical: Why are there leftover screws?

So maybe it’s seminar series or a 2-credit class.  Upon completion, students are given a license to use rotary vane pumps.  The lab practical will be graded pass/fail, with failing students relegated to using old rotary evaporator diaphragm pumps.

 

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Why do we say that?

We chemists love our jargon.  Oftentimes for good reason; it would be cumbersome to describe a material as “having a tendency to absorb moisture from the air” over and over again.  Instead, the word hygroscopic gets the point across succinctly.  Examples of this sort of jargon abound, with the IUPAC Gold Book defining some 6400 unique terms.

The type of language that’s used in the chemical literature actually gives us a window into the work being done over time.  A while back Stu compiled 115 years of JACS article titles into word clouds binned by decade.  The result?  A visual representation of a century of chemical research.  While you see words like “synthesis,” “stereochemistry,” and “nano” reflecting changes in research interests over the years, you also see steady usage of words like “new,” “efficient,” “direct,” and “novel.”

This brings up a second set of chemistry jargon terms which generally do not describe specific and well-defined concepts.  Instead of jargon, one might just call these terms adjectives common in the chemical literature.  We like to poke fun at the use of words like novel, concise, and robust.  Who gets to decide if a preparation is concise, or if a given synthesis is more or less robust than those that preceded it?   After all, there’s more than one way to talk about synthetic efficiency.

Bringing me to my topic du jour, just today I came across the umpteenth paper ascribing the mechanism of a particular reaction to the “steric and electronic properties” of the starting materials.

sterics

16,000+ results, see I’m not crazy

What other kinds of properties can reactants have?  Aren’t all properties just emergent from either sterics or electronics?  The chemical-reductionists among us would argue that all properties are emergent from quantum mechanics anyway:

It’s not factually incorrect to say that a reaction behaves the way it does because of sterics and electronics, but that description could apply to literally every reaction.  Find me a reaction mechanism that isn’t governed by S&E, and we’ll talk.  This kind of language treads dangerously close to the territory of the not even wrong.

The S&E argument, like many other broad but factually true statements from the literature, is in all likelihood just a euphemism for “it is what it is.”  Maybe it’s time to assemble a list of useless phrases for a literature bingo game…

What’s another (kilo)gram?

Prior to my current post, I’d not given too much thought to scale up.  I suspect to the majority of early career synthetic chemists, “large-scale” is synonymous with breaking out the one-liter round bottom flask.  That’s pretty much the comfortable upper bound of what you can work with 1) on a benchtop; 2) with magnetic stirring; and 3) with a oil bath heat source.

Your efforts on this scale will yield somewhere in the ballpark of 100 grams of product, depending on formula weight and a slew of other variables.  And what’s more, purification and workup has now ventured into the realm of things that are no longer routine.  A one-liter reaction volume is going to require a rather large separatory funnel (as a side note, Chemglass sells them up to 22-L — good luck with that).  And unless your starting materials and product have wildly different silica affinities, you’re going to have quite a bit of fun trying to run a 100-gram flash column, so you’ll likely have to break it into a couple runs.

And that’s all great until you need to crank out a kilogram of material.  You can now forget about running things in round bottomed flasks (Chemglass also sells a 22-L round bottomed flask, a testament to the age-old adage “just because you can does not mean you should“).  You’re also not going to have much luck trying to fit a vessel that size onto a hot plate, so that rules out both magnetic stirring (which would be ineffective anyway) and conventional heating baths or mantles.

Things like efficient mixing and heat transfer — which we hand wave away at the gram-scale — start to matter quite a bit once you cross the kilogram threshold.  So you’re going to need a specialized, jacketed reactor, through which you can recirculate a heated (or cooled) thermal transfer media.  And because surface area to volume ratios are the way they are, the temperature gradient between the outside of the reactor and the inside can be pretty dramatic.  So you’ve really got to get things mixed well, which means you need motorized stirring and a decent sized impeller.

Next on your synthetic checklist is workup, which now takes an entire day in and of itself.  Pray you don’t need to purify anything chromatographically.  Your precipitation that required 10 ml of solvent X per ml solvent Y suddenly won’t fit in any container in the lab, save the 55-gallon waste drum.  I’m not ashamed to admit I’ve MacGyvered a workup involving a 5-gallon orange Home Depot paint bucket at a previous position.

All this, and I haven’t even touched on time yet.  Everything at the kilo-scale takes longer.  A reaction which you could comfortably set up in 20 minutes at the gram scale will take you all morning to get going.  And you’d best triple check your work here, as mistakes on this scale are costly.

Of course, the proper process chemists will scoff at the struggles of the kilo-scale.  Steel reactors replace glass, drum evaporators replace rotavaps, and somehow I doubt the tried and true paint bucket workup would pass cGMP muster.

Inventories of the chemical variety

I’ve been thinking a lot about chemical inventory systems recently.  Derek’s post yesterday made for an interesting read, especially the comments section.

Over the years I’ve seen most combinations of storage systems described there.  But what I’m much more interested in now is the software (or lack thereof) which runs these systems.  There’s no shortage of LIMS vendors out there.  There are even some free app-based inventory management solutions that I’ve played with (see Quartzy), which may work well for a small academic lab but lack functionality required by a modest sized company.

There’s a constant struggle, as others have pointed out, with compliance in any inventory management system.  The more work you require of a scientist to use the system, the more likely they are to ignore it entirely.  Barcoding, or more recently RFID tagging, attempt to alleviate some of the burden with logging and tracking materials.

But these attempts to automate inventory management all seem to suffer from what I’ll dub the problem of granularity.  The granularity problem is simply that for an inventory management system to be useful*, it must be sufficiently granular to describe the location of a material with both precision and accuracy.  In other words, a system which correctly identifies the location of a bottle of pyridine as “Chemistry lab 1,” is not precise enough to be useful.  Similarly, a full site map placing that bottle of pyridine in Bin 1, on Shelf 2, in Flammable Cabinet A, in Chemistry lab 1 is only useful if John Smith hasn’t used the last of it and forgot to remove the container from the inventory.

One might envision a system in which each storage location is fitted with an RFID reader, and each reagent bottle tagged with chip (which cost less than a quarter each now).  This system would be able to identify where exactly each reagent is simultaneously, provided it’s within range of an RFID reader.

And indeed, it seems like something like this has been done at least once.  The issue I envision with such a set up is one of granularity — you can’t practically put a reader in each bin on each shelf of each cabinet in your entire facility.  That being said, such a system would probably be able to distinguish whether or not a particular reagent is in the proper flammable cabinet, or if John Smith moved it to his fume hood.

My searching hasn’t uncovered any turnkey solutions involving RFID chemical tracking — but it must be possible if not feasible.  After all, manufacturing operations and logistics companies have been employing this sort of technology for years.

Readers, what’s the best inventory system you’ve seen employed?  Have you ever seen a system that manages to solve both the granularity problem and the compliance problem simultaneously?

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*There are inventory management systems that are not useful, and serve simply to allow administration to be in regulatory compliance.

Acide paratoluènesulfonique

Today I’m back in the swing of planning out more traditional multi-step organic syntheses, which is something I have’t done in a while.  Of course a major part of that is combing through the literature — and dealing with all the idiosyncrasies that entails.  Right off the bat, I noticed that Reaxys doesn’t play terribly well with Google’s Chrome browser, something I’d never encountered before being a member of the SciFinder tribe.

One of the other considerations of perusing the synthesis literature is deciphering the myriad of acronyms used by authors.  It’s rather inconvenient to type tert-Butyl(chloro)diphenylsilane over and over again, so we’ve usually use “TBDPSCl” for short.  This, and many other short hands are universally known in the field.  And there are whole lists of common ones.  But every once in a while you come across one you’ve never seen before.

Enter “APTS.”  From a paper on synthetic a-galactosylceramides, we see APTS used in combination with benzaldehyde dimethyl acetal to selectively protect the 4 and 6 positions in galactose.  My early morning, caffeine-deprived brain failed to notice the Abbreviations section at the end of the paper and began scouring the internet for traces of APTS used in the chemical literature.  Undeterred, but finding only apartment listings, I noticed the author affiliations — all authors are from non-US institutions, and one in particular from Institut Parisien de Chemie Moleculaire in Paris, France.

Knowing APTS must be some sort of acid catalyst, and having a very broken understanding of the French language, two and two were put together and APTS became acide paratoluènesulfonique, or para-toluenesulfonic acid.

The Wikipedia page for para-toluenesulfonic acid does list “PTSA” as an acronym, but I think I’ve only seen it written “TsOH” or “pTsOH.”

I do not feel very American

 

It’s remarkably difficult to parse my personal feelings about my country and the democratic process with the fact that half of my countrymen observed exactly what I did and reached the opposite conclusion.

As a scientist, I look at data for trends and use what I observe to reach conclusions.  I like to think I’ve gotten pretty good at doing this.  The apocalyptic hellscape repeatedly described by DJT is not one that really exists.  This is borne out in the data – crime is on the decline, the economy is growing – things are getting better.  The conclusion I drew from the last eight years of data is the trajectory we are on is fine.  Perfect?  No.  But incremental improvements were making it better all the time.  For everyone.

As a human being, I look at things said and done by each candidate and determine how they mesh with my worldview.  It’s hard to know if I’m particularly good at this.  Trump’s political brand is one of exclusion, and fear.

Exclusion and fear are not American values.  It is a difficult day to be optimistic.  I do not feel very American.

Breaking radio silence

Hi all

It’s been awhile since I’ve posted anything here — apologies.  Lots has been going on as of late.  The most significant news is that after much consideration, I have vacated my old position and switched gears to some new science at a smaller company.  Readers of the blog will remember I’ve spent the better portion of the last three years working on, and blogging about, explosives.

Now I’m at a biotechnology startup, still doing chemistry — albeit completely different chemistry.  I’m not entirely certain the direction I’m going to take this blog, although I do plan on updating more frequently.

I’ve also decided the blog name was getting a bit stale; “The Unemployed Chemist’ was a holdover name from when I was actually unemployed and looking to break into the field post graduation.  So without further ado, let me welcome you to Benchtop Thoughts.  And if you’re stuck in your ways, don’t worry, as the old URL will still redirect here.

More to come soon

Mitch