Category Archives: Chemistry

The ARC, the CHETAH, and the Organikker

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Just received a copy of CHETAH 8.0.  This is a program for thermochemical and energy release evaluation and is distributed by ASTM. It will calculate enthalpy of combustion and thermochemical properties of compounds and reactions including- LFL, LOC, MIE, lower limit flame temperatures, maximum flame temperature, fundamental burning velocity, and quenching distance.

I have only had it installed for 2 days, so it’s way too early to give an appraisal. It came highly recommended by several colleagues in the process safety field.  The only snag so far is a balky SMILES input module. This feature was very appealing because it allows one to copy a ChemDraw structure in SMILES format and paste it into the CHETAH GUI. The rep at ASTM gave me a link which ended up offering very cryptic instructions. Naturally, the problem is some obscure setting in Windows.

Until I get this fixed, I’ll have to enter Benson groups by hand. As it happens, I began studying guitar in my spare time, so there are all kinds of new things for my addled brain to stumble over assimilate. So when I’m not picking at strings, I’m picking at Benson groups.

Update 3/5/09:  After a service pack download, the SMILES module is functioning. This is a very powerful tool.

We’ve recently caught up with the times and have been pressing Accelerating Rate Calorimetry (ARC) into service. Or more accurately, paying to have the data collected.  ARC is really quite informative in that it can offer a Time to Maximum Rate (TMR) equation from which a TMR can be determined for any desired temperature. You can calculate an adiabatic delta T as well. I do not know how reliable this number is, but it certainly reminds one of the importance of considering the effect of phi factor in process scale up.

The ARC data I get includes an Antoine curve which can indicate that the accelerated rate behavior is or is not characteristic of classical liquid/vapour equilibrium behavior. What this says to the wary is that other volatiles (besides the subject material) may be generated which are not condensable. This is helpful in considering what kind of controllability is available to the process engineers.

Djerassi-v-Trost. Clash of the Titans.

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The January 26, 2009 C&EN has an interesting letter to the editor. Carl Djerassi sent a letter critical of the manner in which Professor Trost cites authors in his references. According to Djerassi, Trost didn’t cite the discoverer of a natural product for which the Trost group had just reported a total synthesis. He took Trost to task in diluting the accomplishment of the workers who had isolated, characterized, and tested the compounds for biological activity by not citing the original work.

Trost’s treatment of Pettit is particularly egregious given the well-known fact in the chemical community that the spectacularly laborious decade-long efforts of one of the heroes of marine natural products chemistry—the person who personally collected the bryozoan, isolated the bryostatins, established their constitution, and pursued their anticancer activity against all odds—were terminated through a draconian closure of his laboratory by the new administrators of Arizona State University. [C&EN, Jan. 26, 2009]

Trost and Djerassi are two of the rock stars of organic chemistry. When such people “go nuclear” in their open personal criticism, it is so compelling that you can’t help but take notice. Far from being unseemly, I think this kind of thing is healthy for the field. Neglecting key early workers while trotting your own references up to the front of the line is a kind of misdemeanor racketeering of scholarship. If true, Djerassi has a good point.

But, I can sympathize with Trost to some extent. Eventually, past progress becomes part of the background. Do we have to cite Henry Gilman everytime we use BuLi to remove a proton? There must be some juicy backstory that has Djerassi riled.

Plea from China

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I don’t know what others are experiencing, but I am flooded with desperate email pitches from Chinese chemical manufacturers- “Please, let’s make cooperation!”  Everything from solvents to generic drugs.

A receding tide beaches all boats.

Update:  Just got an offer for bulk Vinblastine Sulfate. Golly, I think I’ll decline. The last thing a guy needs is a few kg of that stuff sitting in a cabinet.

Transformative Research in Many Ways

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A friend who is presently on sabbatical has started a blog about his academic experiences in primarily undergraduate institutions (PUI). It is called Sabbatical Epistles. He mentions a key phrase that is being batted around; it is Transformative Research. According to the NSF, transformative research is-

research that has the capacity to revolutionize existing fields, create new subfields, cause paradigm shifts, support discovery, and lead to radically new technologies.

The context of the use of this phrase was that research funding at PUI’s will increasingly be put to the merit test of transformative research. As such, research into chemical synthesis at PUI’s is especially at risk of not qualifying for funding. I suppose the concern is that multistep synthesis projects for undergrads requires lots of time and skills that undergrads do not have.

Who is against transformative research? It is like motherhood and apple pie. Everybody wants to fund or be part of this kind of effort. We should always ask that research funds be put towards this end. But there is more to it than just an affirmation of meritocracy.

What I sense is that the golden age of undergraduate research programs may be fading into some darker period of scant interest.  The scientific establishment continues to grow larger with each passing year. And in parallel, major research universities continue to add programs, courses, grad students, faculty, bricks and mortar, and administration based on the allocation of grant money. Big institutions depend on grant money to a large extent. 

As grant money gets tighter, program requirements will increasingly filter the small fish from the big fish. Large institutions have many alumni in influential positions and in the end, the programmatic mind-set of large research institutions in conjunction with the definition of success as understood by administrators of first tier schools will win the day. 

There is a pecking order to this. A kind of snobismus. And undergraduate research is not too high in the pecking order.  In relation to undergraduate research in the area of synthesis, in most schools this is the only opportunity for an undergrad to get some advanced experience in the synthetic arts. If you have tried to hire a synthetic savvy BA/BS, you know they are hard to find. In my experience, most synthetikkers want to go to grad school. They want more.

Just in case anybody is listening, I want to make a pitch for continued and stronger funding of undergraduate research. As a student, it changed the course of my life in terms of growth and development. As a former mentor of undergraduate researchers as a post doc and prof, I can say that nearly all of my students are now either PhD’s or MD’s. They are all contibuting greatly to the benefit of our society in industry, teaching hospitals, and academia. I am proud of them and I’d do it over in a heartbeat.  The pedagogy isn’t in dispute, I suppose. But the method of funding is.

Calamity, Interrupted

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JOC will no longer appear in my mailbox. I decided to let go of this icon of my earlier years. Organic Process Research & Development will “arrive”, but this time I have taken a web subscription for $40/year. In the interest of domestic harmony, the rate of paper accumulation will drop somewhat.   The trouble with this form of access to the literature is that I can’t take a journal to the local taco joint where I lunch on occasion.

The recent subscription, the Journal of Loss Prevention, is quite interesting. Lots of articles on the dynamics of explosions and fires as well as studies on calamaties, disasters, and general industrial mayhem. I can dig it.

Both imagination and knowledge are an important part of chemical process safety. A process safety person should have a solid chemistry background to grasp what is happening in a reactor or piece of equipment. Imagination comes in to play when trying to anticipate failure modes leading to initiation and propagation of incidents.

It isn’t possible to anticipate all possible failure modes in a chemical process. And not every failure leads to an incident or casualty. What is possible is to collect as much information as you can for a group to do a process hazards analysis.

A properly facilitated group can unearth many possible failure modes and root causes. Once identified, an effort to remove initiation sources or uncouple possible propagation pathways can be made. The first and best goal is to eliminate a hazardous condition. Management and engineering controls should always be secondary to elimination of a hazardous condition. 

AIChE is a great source of information for process safety.

Update:  The web subscription is quite agreeable to use.

Gold Refining with Borax

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According to the GEUS, the Geological Survey Office of Denmark and Greenland, it is possible to concentrate and isolate gold from the ore using borax and charcoal. This method has the immediate benefit of making mercury “redundant” in gold isolation.

Extraction of gold by amalgamation with mercury is a simple means of producing metallic gold in the field.  After contact with gold enriched ore, mercury is evaporated into the air by direct application of a torch flame to the puddle of metal leaving purified gold metal.

It is thought that there are millions of miners who scratch out a subsistance living working a small patch of ground for gold. It’s called small scale mining. In the course of this activity, environmental contamination can accrue to the immediate area as well as the watershed at large. Sadly, the toxicological insult to the miners from exposure to mercury vapor can be severe.

This method is an inexpensive and simple alternative to the mercury process. Perhaps the chemistry community has something to contribute by way of education or improved methods of extraction.

8/25/10  Update.  I have revisited this post and am compelled to comment further.  While I am unable to offer a good chemical explanation for the effect of borax on gold ore, I can say that the use of borax as a flux  for smelting goes back to the 19th century during the American gold rush period.  The process described in the link appears to be a smelting process for enriched ore containing elemental gold, as opposed to sulfide, or sulphuretted ore. The function of a flux is to modify the flow and phase separation properties of host rock so as to partition away from the gold phase or layer.  In other words, a flux modifieds the slag to help the gold to separate cleanly from the rock.

Lipid Rafts

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This morning I found out what a “lipid raft” is. All of these years I’ve been in the dark about order and disorder in cell membranes. I didn’t learn about this through any sort of noble quest; I was merely curious about a movie.

Molecular Movies is a website containing links to a marvelous set of animations about cells and molecules. I enthusiastically recommend that the reader visit this site. The movie mentioning lipid rafts is in “The Inner Life of the Cell“.

Make or Buy? Gaussling’s 11th Epistle to the Bohemians.

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The most important reaction in chemistry is the one in which you transform chemicals into money. Some chemicals convert into a lot of money per kg, others not so much. The kind of money you want to focus on is profit. Just turning cash over at cost wears thin rapidly and is hazardous to your career. At the end of the day, after you’ve paid the raw mat vendors, payroll, and the feds, you want to have a steaming heap of luchre left over as profit.

At some point in the game, everyone in fine chemical manufacturing realizes that you can’t make everything in-house. There are good reasons to consider making as many intermediates as you can. When you buy an intermediate, the vendors price (cost + profit) becomes the cost you plug into the economics. Optimally, you might be able to make the material cheaper than buying it … eventually. But some raw materials are deceptively simple looking. A company can rack up a lot of brain damage and wasted time trying to make certain kinds of materials outside of your skill set.

We used to joke that at some point in process development, you have to shoot the chemist and get on with scale-up. Often, the decision to make-or-buy an intermediate gets to the table only after you try to make it. In process development, it is important to identify the make-or-buy decisions as early as possible. This can save valuable time. While you may end up spending more per unit mass for the material, not having to make it is equivalent to opening up extra capacity in your facility. Ideally, your want precious reactor/equipment hours spent on the highest value added steps. With each successive step, the value of the intermediate becomes greater.

If your make-or-buy decision revolves around a known item of commerce, then the economics and scheduling is relatively easy. You will have to settle on specifications, delivery schedule, shipment details, and pricing. If the material is not TSCA listed, then you will have to get the vendor moving early on a filing with the EPA, if they are in the USA. If you intend to import a non-TSCA listed fine chemical, not for pharma, ag, food, or other covered use, then the importer of record is responsible for the TSCA paperwork. This can take a few months of lead time.

But if the compound is novel and/or proprietary, then it is instantly much more complex. Not only do you have  to deal with the EPA on TSCA filing, but you have to find a vendor who is willing and able to ramp up a new process. They will need specs, projected delivery information, an agreeable price, and quite possibly a lined-out process and analytical methods. If the vendor has available capacity, this might happen as quickly as 3-4 months. More likely than not, this can take 6-9 months.

If your raw material is part of a critical technology or major account, then you may have to consider dual sourcing. If one plant goes down or the quality or delivery drifts beyond what is acceptable, then you still have one facility that can deliver. And, if you have two vendors, you can start a dandy little bidding war between them for your business. Many companies require their purchasing managers to qualify two vendors for crucial materials. You can argue that you should always have two vendors, but many times the amount of business the material feeds into is too small to bother with.

Chemical manufacturing is much more than reaction chemistry. A chemist in manufacturing can find him/herself involved in many kinds of work.   Regulations, chemistry, process safety, engineering, packaging issues, IP, marketing, and process economics add up to the knowledge set that a chemist needs to acquire while heading up the career ladder.

Bye Bye JOC

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I’ve decided that I’m going to let my subscription to Journal of Organic Chemistry lapse. It’s getting too expensive and they’re accumulating in my house at an alarming rate. The spouse unit is beginning to dig in her heels. My kid thinks it’s normal to have chemistry journals and molecular models all over the house.

Instead, I’ve subscribed to Journal of Loss Prevention in the Process Industries. Much of my time is taken up with process safety and reactive hazards these days, so I may as well accept the transition. I’ll probably subscribe to OPR&D as well. It feels strange, though. I’ve had a JOC subscription since  my junior year in college in ’82/’83.  Carrying around stacks of journals is like carrying around blocks of wood. And, after a while the collection gets a little … odd.

Reactivity and Risk. Gaussling’s 10th Epistle to the Bohemians.

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A chemical plant performing synthesis is a place where the materials in use are purposely selected for certain attributes of instability. Chemical stability refers to the tendancy of a substance to remain unchanged when exposed to some kind of stimulus. That stimulus may be exposure to heat energy, mechanical shock, or a more precise chemical attack on particular functional groups. Unstable substances have a low threshold to change. Stable substances require more stimulus to cause a change in composition.

Substances that are extremely stable are often not very useful in near-ambient temperature chemical synthesis, i.e., saturated hydrocarbons, metal sulfates, silica, etc.  The lack of lower temperature reactivity (say, up to 200 C) can be compensated for by application of high temperatures. Petroleum refineries take full advantage of high temperature reaction chemistry to alter the composition of otherwise stable hydrocarbons.

We choose stable substances for duty as solvents, diluents, carriers, etc., precisely because of their non-changeability or stability. “Inert” solvents allow chemists to bring molecules into solution for selective transformations. Of course, we all know that most solvents have some influence on the course of a transformation, the point is that we can transform solute materials without the fuss of altering the solvent too.

Chemical synthesis requires the manipulation of reactivity (and therefore stability) to perform useful transformations. Without well placed instability on a molecule, there cannot be efficient, directed synthesis. It is the job of the synthesis chemist to apply the knowledge of reactivity.

Because of the inherent instability of reactive and flammable materials, chemical plants must require that certain behaviors, procedures, and knowledge be set into a formal structure. Actions and conditions must give predictable consequences. This structure is comprised of a set of standard- operating procedures, equipment, test methods, and safety requirements.

It seems silly to go to the trouble of detailing the merits of running a safe plant, but it is worth pointing out the layers of requirements on an operating plant. 

  1. Preservation of life, health, and the environment
  2. Compliance with federal, state, and local regulations
  3. To provide for the uninterrupted flow of goods and services in the conduct of business
  4. To qualify for affordable business insurance
  5. To be a good neighbor and stable source of gainful employment for all concerned

A company in the business of manufacture is exposed to many kinds of liability. A chemical manufacturing plant is subject to modes of failure and liability that set it apart somewhat. 

One result of chemical manufacture that sets it apart from other forms of industry is the combination of unknown risk and dread fear. For communities in the vicinity of chemical operations, fear comes from the combination of the unknown as new risks, unknown effects, or delayed effects with the dreaded possibility of catastrophic or fatal consequences, inequitable consequences, involuntary effects, and high risk to future generations (see: Perilous Progress: Managing the Hazards of Technology, Edited by Kates, Hohenemser, and Kasperson, 1985, Westview Press, Boulder, Colorado, p 108. ISBN 0-8133-7025-6).

While the neighbors of a furniture factory may be annoyed by the presence of a nearby woodworking shop, it is unlikely that the neighbors will be stirred into existential dread by its presence. The hazards of a woodworking plant are easy to imagine and therefore, easier to rank into the grand list of life’s dangers.

Chemical and nuclear risk perception score at the extreme ranges of risk perception. Both domains involve an agent of potential harm that is poorly understood by most people. Ionizing radiation is inherently destructive to tissues, but the exact relationship between quality and dose to risk is fuzzy at low level exposure. And because it cannot be sensed directly, fear of it’s presence can induce disturbing excursions of imagination and dread.

Fear of chemicals is widespread in the industrialized world. The downside to chemical operations has been immortalized by numerous well known industrial calamities like Love Canal (Hooker Chemical), Bhopal, numerous dioxin fiascos, PCB’s, or occupational exposure to asbestos or chromium (VI). There are a great many chemical items of commerce that are unavoidably hazardous to health.

Because of the risks associated with toxicity or exposure to hazardous energy from machines, chemicals, radiation, heat, noise, gravity, sharp implements, etc., the many layers of government have established agencies and a regulatory structure to diminish risk exposure to workers specifically and citizens generally.

The purpose of the chemical industry is to produce goods and services for people who want or need the value of it’s output. Like the ad says- “We don’t make the surfboard, we make it better”. Well, making the surfboard better inevitably requires that certain kinds of hazards be unleashed and managed. The expectation that hazardous materials can be eliminated in manufacturing is a fantasy. The manipulation of instability is inherent to chemical transformation. Zeroing out hazards has to come from the demand side of the market.