Lamentations on Chemistry

Thanks to a friend in Grand Rapids, I was linked to a blog hosted by the NY Times called Tierneylab.com.  The writer of the post was sounding off about a pet peeve relating to the use of the term “Organic”.  It seems that there is some confusion as to the use of the adjective organic in relation to certain carbon-containing substances. Tempest in a teapot, you ask? Let the chemistry community decide.

The problem begins to show itself when astronomers and planetary scientists start describing carbon containing materials found in planetary exploration as organic.  Back on earth, the word organic is burdened with both common and scientific usage. So, when descriptions of organic materials found on other worlds begin to arise in discourse, the intent of the usage becomes unclear.

For instance, it could suggest to people that such discovered materials were put in place by some kind of life form. It could suggest to nondiscriminating audiences that the presence of carbon implies life, past, present, or future. Or it might well suggest to higher level audiences that biology-ready raw materials are in place.

The scientists working with the Phoenix Lander have an interesting analytical chore in front of them. Using a robotic platform on Mars, they want to distinguish the presence of organic vs inorganic carbon. What is meant by organic and inorganic is less than clear. But it seems that organic refers to something other than CO2 and carbonate.

In the relatively few journal articles I’ve seen relating to this, the authors are not always precise about the kinds of molecules they are referring to as organic. Irrespective of what is said in the articles, when this work gets to a public forum, the meaning behind the word organic becomes even less clear.   

The TierneyLab post does bring up an interesting question about what is necessary for a substance to be considered organic.  Do graphite, diamond, Buckyball, or soot forms of carbon qualify as organic? What about CO2, CS2, carbonates, CO, HCN, or calcium carbide? Does it make more sense to refer to organic and inorganic carbon, where inorganic carbon is defined as … well, what? 

Seriously, what would it be? CO2? Carbon dioxide is incorporated into glucose by plants and this seems quite organic.  Carbonate? This anion is used to balance our blood pH. Our own metabolic CO2 helps to provide carbonate. This product of metabolism should qualify as organic. CO? Well, Carbon monoxide undergoes Fischer-Tropsch reactions to produce aldehydes. This seems very organic as well. Perhaps the target is a substance with C-H bonds?

There is nothing inherently biological about the C-H bond. The Saturnian moon Titan is blanketed with a thick layer of CH4 (methane) and it seems unlikely that it is of biological origin. Indeed, hydrogen is the most abundant element in the universe and carbon the 4th. That hydrogen and carbon atoms could find each other to form trace methane in a proto solar system isn’t too much of a stretch.

Organic and Inorganic Carbon.  How about we just leave it all as organic? 

Here is what I think. It does matter if a scientist or writer is using language in an imprecise way. If writing or speech implies, for instance, that Mars is rich in life giving organic nutrients when in fact Martian organic matter is really carbonate and CO2, then I believe the language must be altered to reflect that condition. A writer should not leave an impression of past or incipient planetary fecundity when in fact the planet may be an inert ball of metal silicates dusted with a bit of carbonate when the 6 torr CO2 atmosphere kicks up a breeze.

The Space Shuttle Program is scheduled for shutdown sometime in 2010. At that time the reusable, tiled spaceplane concept (STS) will be put to rest in favor of the capsule-on-a-rocket design.  According to plans, there will be a 5 year interlude between the retirement of the shuttle and the implementation of a new man-certified lifter. Many have suggested that this idle period with no manned launch activity could lead to a brain drain in the ranks of skilled aerospace workers.

The successor to STS is the Ares Launch system consisting of a man lifter (Ares I) and a cargo lifter (Ares V).  Ares I is a two-stage system that will take a crew of 4 to 6 into low earth orbit. This vehicle will carry  55,000 lbs of provisions and astronauts to the ISS.  Additionally, it will be used to lift a lunar exploration team into orbit for docking with the lander module placed into orbit by the Ares V lifter. 

Ares V is a heavy lifter and is expected to be able to place 414,000 lbs into low earth orbit or send 157,000 pounds of payload to the moon.  Ares V uses two solid rocket boosters derived from STS and a central H2/O2 liquid fueled rocket using a cluster of 6 engines derived from the Delta IV system.

Ares I & V. Photo Credit- NASA

NASA has awarded contracts for this program and work is underway.

What has recently transpired is an alternative system proposed by a group of engineers. This system is called DIRECT, and involves the use of a single lifter called Jupiter.  The Jupiter lifter is derived directly from the STS lifter which consists of two solid rocket motors and a central H2/O2 tank which feeds the shuttle engines.  The DIRECT system would take advantage of existing technology, but with the addition of an O2 tank extension, a cargo section, and a cluster of engines to the existing liquid fuel tank. The proponents of this system claim that their system could get the next phase of manned space flight going sooner, simpler, and safer.

It is an interesting proposal. I hope it gets some serious consideration by the Congress.

C&EN has a web page devoted to a linked bibliography of safety-related letters to the editor. It is worth having a look at.  It is good to have a healthy interest in energetic reactions and incompatible substances.

WordPress shows the blogger what search terms lead the searcher to your blog. One of the searches that lead a reader to this blog was “How to pass organic chemistry”.  Here is my answer-

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Being in the industrial minority in the chemistry blogosphere, I like to point out (on occasion) those bits of research that may catch the fancy of process chemists. Naturally, I wouldn’t presume to speak for all process chemists. But it is possible to draw a few generalizations.

One desirable modification of a process is commonly called “telescoping”.  To telescope a process is to collapse a multistep process into a smaller number of steps or unit operations. The overriding production goal is to reduce the unit cost of a product in terms of $/kg produced without sacrificing purity.  There are many ways to do this. Reducing the cost of feedstocks, reducing the number of direct labor hours, increasing the concentration of reaction mixtures (space yield), reducing overhead costs, etc. 

A reaction step is fairly easy to understand- one change or transformation is one reacton step. A unit operation is a little more arcane. A unit operation includes transformations, but also encompasses handling and isolation steps. Centrifugation, filtration, distillation, decantation, precipitation/xtallization, and packaging are examples of unit operations.

Another operation that is frequently underestimated in terms of its cost is “polishing”. This a phase where the crude product is subject to purification to specifications.  Polishing can be quite expensive. Indeed, taking a 96.5 % crude product to a 99 % spec can be more troublesome and require more skill than the initial synthesis.

There are a great many examples of telescoping and other process improvments in the literature. A reasonable example of telescoping is found in a recent JOC article- Lin, Lu J. Org. Chem., 2007, 72, 9757-9760.  The authors were able to demonstrate a one-pot preparation of triarylmethanes in two steps. The first step involved the addition of an arylboronic acid to an aromatic aldehyde through the agency of a Pd(bpy)2 catalyst. To the reaction mixture was added an “unfunctionalized” electron rich aromatic species. In this case, unfunctionalized means that no special leaving groups were on the ring.

The added aromatic underwent a Friedel-Crafts type alkylation with the intermediate diarylcarbinol to give the triarylmethane product in 57 % to 99 % overall yield.  The authors made a contribution to the store of knowledge in reaction chemistry. But they also had the presence of mind to improve the efficiency of the process as well.

There are some negatives. I don’t think anybody is automatically keen on running large scale reactions in nitromethane. Its explosability should give anyone pause when contemplating a scale-up. And, the third arene needs to be substantially electron rich. The addition of 1,4-dimethoxybenzene drops the yield to 57 %.

There is an old saying in aviation that “with enough horsepower, you can make a barn door fly”.  A friend recently gave me a copy of Principles of Flying, McGraw-Hill Book Company, 1943, published under the authority of the Bureau of Aeronautics, US Navy. I couldn’t resist posting this graphic from p. 88.  [I hope this comes under fair use doctrine of Title 17 Section 107.]

The older aviation training manuals were often written in an avuncular voice that would appeal to farmboys. This Navy manual on flying takes the reader through the basics of Naval aircraft construction as well as aerodynamics. Floatplane construction and controls are particularly well illustrated.

My first airplane ride occured when I was 6. We went to a pancake flight breakfast in an airport hangar in Boone, Iowa. There, somebody was giving airplane rides for a penny-a-pound. This was a bargain price even then. I recall that the event was connected with the Flying Farmers.

My father had a pilots license and as did my cousin up the road. Cousin Verlyn had a Cessna 170 tail dragger that he flew from a pasture on his farm. One day on the rollout after landing he rolled into a pool of standing water, flipping it over and bending the main spar. It never flew again. 

Though my mother worked on her license, somehow she didn’t take the flight test. This was in the early 60’s and manned space flight was all over the news. Americans were going places and to see my father riding with a friend in his Stearman doing aerobatics over our cornfield could only mean to a small boy that somehow we could be a part of the big adventure.

I recently spent some time listening to an acquaintance talk about his days as a student at MIT and as a grad student at Harvard in the early 1950’s.  He had Geoff Wilkinson for inorganic chemistry at MIT as an undergrad and later did his PhD with Wilkinson at Harvard.  Curiously, Wilkinson did radiochemistry in the Manhattan Project prior to joining academia. His radiochemistry experience compelled him to work fast and in test tubes, according to my friend.

My friend’s lab mate in Wilkinson’s group was Al Cotton. They started grad school together ca 1952 or so. This was shortly after the sandwich structure of ferrocene was proposed by Wilkinson’s fellow Harvard prof R. B. Woodward. Woodwards basis for this structure was on symmetry and a single IR stretch absorption. Spectroscopically, the original sigma bonding model didn’t fit the data.  Just prior to this, Wilkinson had begun work on a variety of organometallic Cp compounds. As the story goes, when Woodward expressed interest in making more Cp compounds, Wilkinson went to his office and “had words” with Woodward. Afterwards, Woodward moved on to other things.

My friend laughingly recalls the time he was chewed out by his P-Chem prof, the great George Kistiakowski and earlier, by Arthur Cope at MIT. He recalls being summoned to Cope’s office. Cope was wearing pink slacks which contrasted with his red hair. He was displeased about the impertinent back channel invitation my friend pitched to Linus Pauling to speak to the chemistry club. (I haven’t verified the color of Cope’s hair)

My friend recalls having E. J. Corey as a lab assistant while in an undergraduate lab at MIT. He joked that he saw Corey once at the beginning of the term and once at the end. My PhD advisor, Al Meyers, did his post doc with Corey some years later. Small world.

An interesting bit of chemistry was published by Berit Olofsson at Stockholm University in a recent JOC. The Olofsson lab has previously produced a method for the one-pot preparation of diaryliodonium triflates. This latest work provides diaryliodonium tetrafluoroborates (JOC, 2008, 73, 4602-4607). 

The preparation of I(III) compounds usually starts with an Ar-I compound undergoing oxidation followed by an electrophilic addition/substitution to another arene. Regioselectivity is obtained by choosing a donor with a leaving group such as a boronic acid, stannane, or silane.

What is clever about this process is the fact that a BF4 salt is directly produced. Two equivalents of boron trifluoride etherate are used in the reaction which evidently results in some kind of disproportionation producing the BF4 counter-anion. 

It is known that the reactivity of iodonium compounds is somewhat sensitive to the coordinating ability of the counter-anion, so BF4 is less undesirable than other choices (like chloride). Solubility is greatly influenced by the choice of counter-anion as well. This is particularly true in photo-initiator applications where the choice of carrier fluid may be limited.

The recent issue of Journal of Organic Chemistry, (JOC, 2008, 73(12)) has a few articles that are particularly interesting.

The article by Lipkus, et al., entitled Structural Diversity of Organic Chemistry. A Scaffold Analysis of the CAS Registry, JOC, 2008,73, 4443-4451, is a particularly ambitious bit of work that only CAS could do. This article describes a scaffold survey of more than 24 million organic compounds in the CAS Registry.

The data set was limited to carbon-based structures containing the heteroatoms H, B, Si, N, P, As, O, S, Se, Te, and the halogens.  Moreover, the work was further limited to framework structures containing rings or linked rings. Acyclic compounds were not included owing to the inapplicability of the framework definition in the search algorithm. Multicomponent substances and polymers are ignored as well.

Lipkus and coworkers found that half of the graph frameworks analyzed are described by only 143 framework shapes.  The remaining half are described by 836,565 graphs.

One of the key conclusions is quoted here-

“It is not surprising that some frameworks occur much more frequently than others. However, the extreme unevenness in the way frameworks are distributed among organic compounds is somewhat surprising. This is particularly true at the graph level, where it is found that only 143 framework shapes can describe half of the compounds. The fact that both graph and hetero frameworks have very topheavy distributions tells us that the exploration of organic chemistry space has tended to concentrate on relatively small numbers of structural motifs.”

Lipkus concludes that cost minimization is one of the drivers of this “… shaping the known universe of organic chemistry.” He comes to this conclusion due to the presence of a power law which describes this distribution. The power law he refers to is a linear log-log relationship that is indicative of what they refer to as the “rich-get-richer process”.

If I understand this correctly, a relatively small number of easily made or commercially available early precursors are comprised of ring graphs that, by virtue of modification, propagate into more complex analogs that retain the original graph. This has the effect of multiplying the frequency of a given graph.

The cost minimization aspect comes from the benefits of familiar chemistry and the commercial availability of a fairly limited set of ring graphs. Adding more rings will usually mean adding more molecular weight and adding problematic synthesis and separation issues.

The authors conclude that the lopsided distribution of organic compounds toward only 143 graphs comprises a bottleneck in drug discovery. They further suggest that more exploration in other areas of chemistry space may be worthwhile.

Here is a link to “Watts Up With That?”  This is a very interesting blog on weather related matters. The writer has a very level headed view of climate change. This particular link relates to recent trends in atmospheric water content as a function of altitude (in millibars).