Category Archives: Chemistry

A Bit of Fentanyl Chemistry

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A recent raid on a clandestine drug lab in the Hatzic Valley east of Vancouver, BC, netted 25 kg of “pure” fentanyl and 3 kg which had already been cut for street use. Precursor chemicals used to manufacture the fentanyl were also seized. Along with the drug, the raid also seized 2,000 liters of chemicals and 6,000 liters (about 30 drums) of hazardous chemical waste, according to an RCMP news release 2 November, 2023.

The police said that the seizure represented 2,500,000 street doses.

In August of 2023 the police in Hamilton, Ontario, announced the results of Project Odeon. This was a large-scale sweep of illicit drug production in the Hamilton and Toronto area. From January 1, to July 30, 2023 there were 606 incidents related to suspected opioid overdoses and 89 suspected drug related deaths in the Hamilton area. Twelve people were charged for a total of 48 criminal charges. The police disclosed the following items that they seized-

  • An operational fentanyl drug lab at 6800 Sixteen Road, Smithville.
  • A dismantled fentanyl drug lab at 4057 Bethesda Road, Stouffville.
  • Approximately 3.5 tons of chemical byproduct from fentanyl production.
  • 800 gallons of chemicals commonly used in the production of fentanyl
  • Lab equipment commonly used in the production of fentanyl
  • 64.1 kg of illicit drugs, including 25.6 kg of fentanyl, 18 kg methamphetamine, 6 kg of ketamine
  • A loaded, Glock firearm and ammunition and four extended magazines
  • Over $350,000 of seized proceeds, including cars, jewelry, furniture and cash

Fentanyl is a synthetic drug first prepared in 1959 in Belgium by Paul Janssen (1926-2003). Janssen was the founder of Janssen Pharmaceuticals, now a subsidiary of Johnson & Johnson. In addition to fentanyl, the Jenssen team developed haloperidol, the ultrapotent carfentanil, and other piperidine based congeners. Piperidine itself is a DEA List 1 substance in the US.

Carfentanil is just modified fentanyl. Graphics: Will O. de Wisp

The elephant in the room with fentanyl is its extraordinary potency as an opioid. In pharmacology, potency is a quantitative measure of the amount of dose needed to elicit a specific effect on an animal or human in terms of dose weight per kilogram of body mass. Potency is subject to variability across a population and rises to an asymptote which can be difficult to pin down. For these reasons potency is reported at 50 %. For highly potent drugs like fentanyl, the measure is expressed as milligrams or micrograms of dose per kilogram body weight (mg/kg or mcg/kg body weight). One milligram per kilogram is one part per million (ppm).

When matters of toxicity arise, it is important to remember the maxim that “the dose makes the poison”. This observation traces back to Paracelsus in the mid-sixteenth century.

 “All things are poison, and nothing is without poison; the dosage alone makes it so a thing is not a poison.”

– Paracelsus, 1538. Source: Wikipedia

Fentanyl acts much like morphine in regard to its affinity for one particular opioid receptor. Morphine is commonly the “standard” with which other opioids are compared. For instance, fentanyl is said to be 50-100 times more potent than morphine. Only 0.1 mg of fentanyl is equivalent to 10 mg of morphine. Carfentanil is more potent still at 10,000 times the potency of morphine.

Morphine is an agonist which activates the μ-opioid receptor. Activation of this receptor with morphine produces analgesia, sedation, euphoria, decreased respiration and decreased bowel motility leading to the earthly delights of constipation. Fentanyl is thought to interact with this receptor as well.

Original fentanyl synthesis by Janssen. Graphics: Will O. de Wisp

So, how is fentanyl synthesized? See the synthetic scheme above. I’ll just comment on the Janssen synthesis and some issues. I have no idea of how it is made out in there by the Mexican cartels and in ramshackle American trailer parks. The synthesis above has some steps that may be undesirable for backwoods or jungle operations like hydrogenation. In the first step, aniline will be needed to make the phenyl imine. It’s pretty toxic and stinks to high heaven. Next, lithium aluminum hydride is needed to reduce the imine double bond to an amine. This innocent looking grey powder is very hazardous and should only be used by an experienced chemist. It is also available as a solution in tetrahydrofuran. The next step is the formation of the amide with propionic anhydride. While the reaction entails a simple reflux, you still have to isolate the product. Once you have recovered the amide, the benzyl protecting group on the piperidine nitrogen must be removed. It allowed amide formation exclusively on the upper aniline nitrogen and has served its purpose. Finally, the piperidine nitrogen must be festooned with a phenylethyl group and phenylethyl chloride was used to afford the fentanyl product. 

An excellent review of the pharmacology and drug design of this family of opioids, see Future Med Chem. 2014 Mar; 6(4): 385–412.

In chemical synthesis generally, substances are prepared in a stepwise manner and with as few high yielding steps as possible. To begin, one must devise a synthesis beginning with commercially available raw materials as close to the target as possible. If the product has many fragments hanging off the core structure, it’s best to solve that problem early. Synthetic chemistry is almost always performed in a non-interfering solvent that will dissolve the reactants and allow the necessary reaction to occur. A low boiling point is preferable for ease of distillation. An important side benefit from a solvent is that it will absorb much of the heat of reaction which can be considerable. Left on its own, a reaction might take its solvent to the boiling point by self-heating, generating pressure and vapor. The benefit from evaporation or reflux boiling is that as a solvent transitions from liquid to vapor there is a strong cooling effect which helps to control the temperature. An overhead condenser will return cooled solvent to prevent solvent loss.

You can do any chemical synthesis in one step with the right starting materials. Unfortunately, this option is rarely available. The next best option is to take commercially available starting materials through a known synthetic scheme. People who run illicit drug labs are never interested in R&D. They want (and need) simple chemistry that can be done by non-chemists in buckets or coke bottles at remote locations. Chemical glassware can be purchased but sometimes the authorities will be notified of a suspicious order. This is especially true with 12 liter round bottom flasks.

The most difficult and risky trick to illicit drug synthesis is obtaining starting materials like piperidine compounds in the case of fentanyl and its congeners. In the case of heroin, acetic anhydride shipments have been investigated for a long time because it is used to convert morphine to heroin- an unusually simple one-step conversion. Solvent diethyl ether is similarly difficult to get outside of established companies or universities. Many other common drug starting materials are difficult to obtain legally in the US or EU by the criminal element. However, China is thought to be a major supplier of starting materials outside the US and EU. Countries with remote coastlines, loose borders, lackadaisical or corrupt law enforcement reduce the barriers for entry of drug precursors. China in particular has a large number of chemical plants that make diverse precursors for legitimate drugs. Unfortunately, some of these precursors can also be used for illicit drugs or existing technology adapted for this use. Precursors can be sold to resellers who can do as they please with them. Agents may represent many manufacturers and can mask the manufacturer’s identity and take charge of the distribution abroad. Shady transactions become difficult for authorities to detect and trace. The identity of illicit precursor chemicals are easily altered in the paperwork to grease the skids through customs. Resellers can repackage chemicals to suitable scale, change the paperwork and jack up the price for export. It has been my experience that many if not most Chinese or Japanese chemical manufacturers conduct business through independent export agents. However, behind the curtains there often a byzantine web of connections between companies and agents, so you may never know who will manufacture your chemical. As an aside, this complicates getting technical information from the manufacturer since the agent will not disclose a contact at that manufacturer.

Highly potent drugs like fentanyl must be taken in very small dosages which means that kilo-scale batch quantities of drug result in many individual sales per kilo. Small quantities of highly potent drugs are more easily smuggled than bulky drugs like weed with its strong odor.

There is a down-side to the illicit manufacture of drugs like fentanyl. It is quite toxic at very low dosages and must be handled with the greatest of care lest the “cook” and other handlers get inadvertently and mortally poisoned. Good housekeeping helps, but I have yet to see a photo of a tidy drug lab.

Fentanyl can be sold as a single drug but perhaps is cut with a solid diluent that some random yayhoo decided was Ok to use. Other drugs of abuse like heroin may be surreptitiously spiked with fentanyl to kick up the potency. In either case, a given dosage may or may not be safe even for a single use. There is no way for a user to know. Also, the concentration or homogeneity of mixed solids may be subject to wide variation. For more than a few people, their first fentanyl dose will be their last.

Chemical Nomenclature, Enantiomers and Polarized Light

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[Reissue under better title]

Due to a recent hospital stay with pneumonia, I found myself staggeringly bored. To stave off some of this I began to look into an antibiotic I was given that I had never heard of- Levofloxacin. The structure of this antibiotic was different from antibiotics I was previously familiar with. Natural I suppose, considering that I’ve been immersed in organo-transition metal chemistry for most of my industrial career. Metal-carbon bonds are quite useful in some sectors but not as drugs.

Levofloxacin is a good place to go deep diving into some of the murkier depths of chemical nomenclature. The complicated-looking chemical naming system exists to unambiguously represent the composition and shape of molecules. Certain features and properties of a molecule confer important attributes that need categorizing, thus requiring descriptive names rather than just a number. Every different chemical substance is, well, different and their chemical names must reveal a unique identity. Two or more substances with the same name leads to nothing but trouble.

Chemical substances can be grouped into categories to associate them with related aspects. We have noble gases, transition metals, hydrocarbons, pnictogens, polymers, acids, and bases etc. But the categories allow for variation when particular attributes are under discussion.

The names of chemical substances can be very off-putting to non-chemists and often does lead them to abandon their search for information. A few have even suggested that if you cannot pronounce the name it must be bad. Even worse than the polysyllabic and numbered character strings are the various synonyms. Consider simple toluene which is actually not so bad-

Directly from Chemical Abstract’s SciFinder.

In chemical nomenclature there is just a bit of flexibility in how numbers, syllables and name fragments can be assembled as the toluene example above shows, if you don’t read the rules too closely. The plethora of names come from historical trade names or long-time industrial use or may just predate systematic nomenclature now in use. There is also the German Beilstein and Gmelin organic and inorganic nomenclature as well, but these seem to be outdated.

As always, a proper chemical name describes the composition and 3-dimensional connectivity of the chemical structure of a molecule. These names are commonly listed in one of the two dominant styles of chemical nomenclature in the world- International Union of Pure and Applied Chemists (IUPAC) and Chemical Abstracts Service (CAS). IUPAC tends to be taught in undergraduate chemistry because it always has been and is maybe a trifle easier.

The CAS databases contain more than 200 million organic and inorganic chemical substances and about 70 million protein and nucleic acid sequences. There are two search platforms available in CAS- SciFinder and STN. STN is much more cryptic and harder to learn than SciFinder. Some say there are weaknesses in patent searching in SciFinder alone. For IP work I use SciFinder, Google Patents and the USPTO in combination. All three offer different kinds of searching capability.

Levofloxacin is a biocidal antibiotic effective against both gram-positive and gram-negative bacteria. It is an inhibitor of both DNA gyrase and topoisomerase IV enzymes which are involved in shaping the geometry of bacterial plasmids, or rings of bacterial DNA. Plasmids have to fit inside the bacterial cell wall and those that are not made compact enough are too long to allow successful formation of daughter cells in reproduction resulting in cell death. Other kinds of antibiotics are bacteriostatic and often work better in one or the other of Gram-Negative or Gram-Positive bacteria. Gram stains are effective with certain types of bacterial cell walls and not with others. The ability of a dye to stain a colony of bacteria a particular way is used to help identify bacteria.

Consider the name of Levofloxacin from IUPAC: (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid hemihydrate. The name is a string of characters with numbers indicating attachment points. The core of the structure is a 1,4-benzoxazine ring system which is festooned with a carboxylic acid and a few other groups. The core structure was identified and numbered previously by someone according to rules. The IUPAC name also specifies that it is a hemihydrate, meaning that there is one molecule of water associated with every two (hemi) molecules of Levofloxacin. For some reason the CAS name does not include the hemihydrate in the name, probably because it was not mentioned in the composition when registered with CAS. How it is in the IUPAC name is not known to me.

More pain. The IUPAC name above indicates “(-)-(S)-“. Molecules with “handedness” are said to be chiral and are not superimposable with their mirror images, similar to a right-hand being shape-incompatible with a left glove. These molecules can be prepared as individuals of single handedness or all of the way to a 50:50 mixture of left and right-handed. A 50:50 mixture of left and right-handed is called a “racemate” (RASS eh mate). Each handedness version is a type of isomer called an “enantiomer“. A substance consisting of a pure enantiomer is said to be “enantiomerically pure.”

Isolated enantiomers have the ability to rotate plane polarized light as measured by a polarimeter. Plane polarized light is a light beam where the electric field vectors of the electromagnetic radiation are all vibrating in a single plane. Obviously the magnetic vectors are polarized as well, but it is the electric field that is usually mentioned. The angle of the oscillating ray’s electric fields along the axis can be tilted one way or the other depending on the interaction with matter. Reflected light and skyglow are polarized as well. Molecules with handedness rotate the vibrational plane and by an angle dependent on the light frequency and the amount of chiral mass traveled through. Light that is rotated counterclockwise, or levorotary, has a (-) sign and signified with an “l” and light that is rotated clockwise is dextrorotary and has a (+) sign and signified with a “d.” If a molecule rotates plane polarized light, the substance is said to be “optically active.” The amount of rotation is dependent on the light frequency, frequently the sodium D line (actually a close doublet) which is often used as the standard source for this. Mercury lines, e.g., 354 nm, can be used if the D line results in a low measured rotation. Substances that do not rotate plane polarized light are often designated “dl” as an abbreviation for racemic.

D-Glucose, or dextrose, solutions rotate plane polarized light in the clockwise, dextrorotary direction, thus the “D” in the name.

Commercial L-lactic acid derived from fermentation is “L” for levorotary. This enantiomerically enriched lactic acid is used to make the lactide monomer for poly(lactic acid), PLA. Only the lactide dimer from L-lactic acid gives the desired PLA isomer. The racemic form of lactic acid is not useful for PLA due to undesirable physical properties in the polymer.

A ratio can be taken from an experimental sample that may range from 50:50 racemate to 100 % of a single enantiomer to give the optical purity of the chiral material, representing the proportion of pure enantiomer. Often the measure % ee, or percent enantiomeric excess is used to describe enantiomeric purity. A 95:5 mixture of enantiomers would have a 90 % excess enantiomeric of one enantiomer. Chemical synthesis of 99 % ee can be quite difficult.

A racemate does not have a net rotation of plane polarized light. The (-) sign represents the “levo” part of the levofloxacin, referring to counterclockwise rotation of plane polarized light. Prior to the appearance of reliable analytical methods for the determination of enantiomeric purity, polarimetry and optical rotation were the method of choice. Today, Gas Chromatography (GC) and High Performance Liquid Chromatography (HPLC) columns and chiral shift reagents for 1H-NMR that can provide baseline separation of enantiomers.

The (S) character in the name indicates the handedness of a molecule as determined by standard selection rules defined by an organization for assigning absolute configuration. “S” stands for the Latin word “sinister” meaning left-handed. There is no simple calculation to go between absolute configuration and sign. The (-) sign can indicate which particular enantiomer is under consideration with an easy measurement if it has been previously correlated. (-)-(R) and (+)-(S) enantiomers can and do occur. The “(S)” defines only the precise configuration of atoms about an asymmetrically situated atom in a molecule based on a few simple rules. The mirror image of (-)-(S)- would be (+)-(R)-, “R” for rectus meaning right-handed in Latin.

The first task in assigning a name to a molecule is to determine the “core” structure. This is the basis of the name. Your molecule will be a variety of “the core structure.” This is not so easy because IUPAC or CAS will have already done this and your choice may or may not match. Referring to the CAS name below, you can see that some structural fragments end in “-yl,” “-ic” or “-o”. These signal that the fragments are not the core structure, they are attachments. The core structure onto which everything else is attached is the “1,4-benzoxazine”. It is a standalone chemical name which may be modified. This is a very obscure fact that most won’t know, but the “-ine” suffix indicates that the core structure is an amine, full stop. Other nitrogen indicators like azo, aza, amino, ammonium, nitro, azido, etc, suggest a nitrogen group attachment to something else.

Does it help to have a college degree in chemistry to know this stuff? Sorry but yes. In the set of all worldly knowledge, this is pretty obscure.

The CAS name for levofloxacin is 7H-Pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid, 9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-, (3S)-. The core structure seems to be the 1,4-benzoxazine. CAS has a ring-system handbook that defines and numbers all of the known ring systems. The significance of CAS is that they assign and maintains the official CAS registry number, CASRN, which is depended upon world-wide for the exact composition and connectivity and geometry of substances. There is a very extensive rule book that rigidly defines a chemical name with rooms of CAS experts sitting in a building in Columbus, OH, to assign these names. For levofloxacin the CASRN is 100986-85-4. Today, CASRNs are usually directly searchable on Google. The final digit “4” is a check digit for error entry detection.

General comments about chemical features on Levofloxacin.

Yet more pain. The more formal official CAS name, however, does not indicate the direction of rotation of plane polarized light. I suppose this is considered experimental data not needed in the name. The CAS nomenclature only shows “(3S)-” in the name, indicating the absolute “S” configuration at position 3 of the molecule. The business of handedness or shape in 3-space of a molecule is called “stereochemistry” and arises in several ways. The rules for assigning the absolute configurations of R or S enantiomers may depend on the features of the molecule.

This business of molecular handedness is mostly an issue for biochemistry and pharmaceuticals. A great many- most?- biomolecules have handedness themselves and are therefore subject to interactions with other biomolecules or drugs that depend on the precise shapes for their interactions. This is very important for the interaction between molecules like an enzyme and substrate or ligand.

In the absence of other chiral molecules, two enantiomers will have the same chemical properties when individually pure. However, a racemate consists of a pair of enantiomers. The interactions between R and R or S and S enantiomers, will be different than the interactions between a racemic mixture of R and S or S and R enantiomers. If there is more than one chiral feature in a molecule- say two- then the molecule could be R, R or R, S, or S, S, or S, R. This gives two pairs of enantiomers, each called a “diastereomer.” For instance, one substance with R, S and another with R,R will be substances chemically and physically different called diastereomers. The presence of a diastereomer in an enantiomeric drug product would likely be deemed a contaminant and removed.

Source: David Darling

A druggable disease-state is one that can be positively influenced by a drug molecule. This commonly involves the drug molecule docking with an enzyme to activate it or deactivate it. These enzymes are very large diastereomers having many chiral atoms giving them complex shapes that can result if the formation of a pocket in the protein structure called the “active site.” This active site has very particular shape and charge features provided by the chiral amino acid chain of the protein. An active site will have a shape that is compatible with the close fitting of a drug or other molecule similar to a hand in a glove. Many of these active sites bind the shape and charge of one enantiomer of a drug molecule more effectively than the other for a better fit. The drug, or substrate, may just sit there and block the action of an enzyme, shutting it down or activate it continuously. Other active sites may bind a drug and change the shape of the enzyme causing the enzyme to speed up or slow down for a throttling or accelerating effect elsewhere on the enzyme. This is called the allosteric effect.

So, you may be asking- big deal, what does it matter? In the world of pharmaceuticals, many drug substances can exist as single enantiomers, racemates or diastereomers. Racemates may be easiest to manufacture, but very often one of the enantiomers is more biologically active than the other. In fact, one enantiomer may be disastrously harmful. The classic example is Thalidomide. The S form caused birth defects and the R form did not. Pure R enantiomer was safe from teratogenicity but a racemic mixture of R and S was not.

Conclusion. A superficial look at a chemical name opens up insights into the chemical nature of a substance. What makes each chemical substance unique is their distribution of charge in 3-dimensions. The distribution is affected by the types of the atoms present, geometric features of the 3-dimensional shape and the ability of the system to allow charge to accumulate in particular places of the molecule. These attributes mentioned also set up the type and vigor of reactivity the molecule will display.

Weed Decarboxylator from Amazon

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So, I get an email from Amazon promoting its “Decarboxylator” product. The Amazon page shows a picture describing the device and shows a picture of someone loading it with spinach leaves. The title of the page says “Decarboxylator Machine to Make Butter, Oil, and More“. A link to ecru, the seller, extols the virtue of herb consumption for greater wellness. The device obviously is just a heated container with digital thermometer and temperature setpoint adjustment.

Source: Amazon.com. One version of the home decarboxylator.

Why bring this up? This was sent to me as an Amazon customer, but I also happen to be an organic chemist who knows about decarboxylation generally. Or, just maybe they know that already?? What on Earth is retail decarboxylation about I wondered. Well, a simple Google search immediately turns up the answer. Processing weed for use in edibles. The silly allusions to vegetable processing is just a ruse.

The decarboxylation of THCA-A to give THC. Graphics: Silly old me.

Apparently, there are two isomers of tetrahydrocannabinolic acid, THCA. They are THCA-A and THCA-B. THCA-A is present is large quantities in unprocessed marijuana. THCA-A is the direct precursor of THC in the plant. When you smoke weed or bake it into brownies the burning or baking process decarboxylates THCA-A giving the psychoactive product, THC. However, when you extract weed with a solvent without heating, the decarboxylation is very slow and affords reduced potency. Weed for edibles must be heat treated to induce decarboxylation for maximum potency. The Wikipedia page on tetrahydrocannabinolic acid is very informative. The THCA-A precursor has its own pharmacological effects which is interesting in itself, but that is for another day.

This handy-dandy whizbang device does the deed for home producers of edibles. Ain’t it grand?

The Illuminating History of Producing Brighter Flames

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This is a reprint of an October 25, 2010, piece that I wrote about illumination with flames. I did tweak the title a bit for the sake of accuracy. -Th’ Gaussling

Until the invention of the electric lamp, the illumination of living and working space was very much the result of sunlight or of combustion.  Since the development of fire making skills in prehistoric times, the combustion of plant matter, fossil fuels, or animal fat was the only source of lighting available to those who wanted to illuminate the dark spaces in their lives.

From ancient times people had to rely on flames to throw heat and an agreeable yellowish light over reasonable distances. A good deal of technology evolved here and there to optimally capture the heat of combustion to do useful work (stoves, furnaces, and boilers) from readily available fuels. 

Lighting technology also evolved to maximally produce illumination from flame.  High energy density fuels that offered a measure of convenience for lamp users evolved as well. Liquid fuels like vegetable oils, various nut oils, whale oil and kerosene could flow to the site of combustion and were in some measure controllable for variable output. The simple wick is just such a  “conveyance and metering device” for the control of a lamp flame. Liquid fuels flow along the length of a wick by capillary action to a combustion zone whose size was variable by simple manipulation of the exposed wick surface area.

The first reported claim of the destructive distillation of coal was in 1726 by Dr Stephen Hales in England. Hales records that a substantial quantity of “air” was obtained from the distillation of Newcastle coal. It is possible that condensable components were generated, but Hales did not make arrangements to collect them.  Sixty years earlier an account of a coal mine fire from flammable coal gases (firedamp) highlighted the dangerous association of coal with volatiles. So, flammable “air’ was associated with coal for some time.

By 1826 a few chemists and engineers were examining the use of combustable gases for illumination. The historical record reveals two types of flammable gas that were derived from coal- coal gas and water-gas. Both gases came from the heating of coal, but under different conditions. Coal gas was the result of high temperature treatment of coal in reducing conditions. It is a form of destructive distillation where available volatiles are released.  Depending on the temperature, there was the possibility of pyrolytic cracking of heavies to lights as well. 

Water-gas was the result of the contact of steam with red hot coal or coke. The water dissociates into H2 and CO. Water gas is a mixture of hydrogen and carbon monoxide, both of which are combustible. The formation of water-gas is reported to have been discovered by Felice Fontana in 1780. 

One of the properties of burning coal gas or water-gas was the notably meager output of light from the flame. Workers like Michael Faraday and others noted that these new coal derived gases provided feeble illumination, but if other carbonaceous materials could be entrained, then a brighter flame could result. It was during the course of investigations on illumination with carburized water-gas that Faraday discovered bicarburet of hydrogen, or benzene.

About this time, an engineer named Donovan also noted that if other carbonaceous materials were to be entrained into water-gas, then the light output was enhanced. So, in 1830, engineer Donovan installed a “carburetted” water-gas lighting system for a short run in Dublin.

Coal gas was first exploited for lighting by the Scottish engineer William Murdoch.  Murdoch began his experiments in 1792 while working for Watt and Boulton in England. By the late 1790’s, Murdoch was commercially producing coal gas lighting systems. His home was the first to be lit with coal gas.

The carburization of water gas eventually became an established industry in America in the second half of the 19th century. The treatment of gases, especially with the discovery of natural gas in Ohio, increased the commercial viability of lighting with gas. Carburization of water gas was aided by the discovery of hydrocarbon cracking to afford light components that could be used for this purpose.

Thorium is frequently found in the ores of rare earth elements (REE) and the connection of REE’s to the issue of illumination begins in the laboratories of Berzelius in about 1825. Berzelius had observed that when thoria and zirconia were heated in non-luminous flames, the metal oxides glowed intensely.  But this was not a new phenomenon. Substances like lime, magnesia, alumina, and zinc oxide were known to produce a similar effect. Goldsworthy Gurney had developed the mechanism of the Limelight a few years before. In the limelight, a hydrogen-oxygen flame played on a piece of lime (calcium oxide) to produce a brilliant white glow.  This effect was soon developed by Drummond to produce a working lamp for surveying.

The work of Berzelius was an important step in the development of enhanced flame illumination. He had extended the range of known incandescent oxides to include those that would eventually form the basis of the incandescent mantle industry.  Thoria (mp 3300 C) and zirconia (mp 2715 C) are refractory metal oxides that retain mechanical integrity at very high temperature. This is a key attribute for commercial feasibility.

Numerous forms of incandescent illumination enhancements were tried in the middle 19th century. Platinum wire had the property of glowing intensely in non-luminous flames. But platinum was not robust enough for extended use and was quite rare and consequently very expensive. By 1885, a PhD chemist named Carl Auer von Welsbach patented an incandescent mantle which was to take the gas light industry to a new level of performance. Welsbach studied under professor Robert Bunsen at the University of Heidelberg. 

Welsbach fashioned the incandescent mantle into the form that is familiar to anyone today who has used a Coleman lantern. The original mantle was comprised of a small cellulose nitrate bag that had been impregnated with magnesium oxide, lanthanum oxide, and yttrium oxide in the ratio of 60:20:20.  The mantle gave off a greenish light and was not very popular.

By 1890, Welsbach produced an improved incandescent mantle containing thoria and ceria in a ratio of 99:1. This mantle emitted a much whiter light and was very successful. Many combinations of zirconia, thoria, and REE metal oxides were tried owing to their refractory nature, but the combination of thoria-ceria at the ratio of 99:1 was enduring.

Welsbach made another contribution to the commercialization of REEs. Welsbach had experimented with mischmetal and was interested in its pyrophoric nature. He had determined that a mixture of mischmetal and iron, called ferrocerium, when struck or pulled across a rough surface, afforded sparks. In 1903 Welsbach patented what we now call the flint.  In 1907 he founded Treibacher Chemische Werke GesmbH. Today Treibacher is one of the leading REE suppliers in the world.

See the earlier post on REE’s.

REE’s in Greenland.

REE Bubble?

REE’s in Defense.

REE’s at Duke.

Big Prize for Quantum Spots

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Poltroon University will soon host a lecture by Big Prize Laureate Dr. Professor Guss Badeen of the Swiss Federal Institute of Quantum Spot Studies in Outerlocken, Switzerland. Dr. Badeen began his work at the Soviet All-Union Agriculture and Artillery Institute in Pissov-on-Don, USSR. After the entertaining implosion of the Soviet Union, Academician Badeen made his way to Switzerland where he is now Emeritus Langweilig Professor of Quantum Agriculture. He will speak on the topic of “My Journey to Sweden with Quantum Spots.”

Admission is free but due to limited seating in the Alderaan auditorium, tickets will be required. Tickets can be obtained online at poltroon_univ.org/QSpot.

Poltroon University is located in Guapo, Arizona, adjacent to the scenic Desiccated Wasteland National Monument. Poltroon is a selective private illiberal arts institution serving the educational needs of junior varsity students. On campus visits are welcome.

Katalin Karikó and Drew Weissman Win 2023 Nobel Prize for Medicine and Physiology

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Congratulations are in order to Katalin Karikó and Drew Weissman for their Nobel Prize winning work with a COVID-19 vaccine using modified mRNA. The image below shows the component changes that were made to the uridine nucleotide. The change to the middle molecule was that they swapped positions of a carbon and a nitrogen atom in the ring and moved a double bond. In the third molecule they added a methyl (H3C-) group to one nitrogen of the pyrimidine ring.

Source: Frontiers in Cell and Developmental Biology 04, Nov. 2021, vol 9-2022 Volume 9 – 2021 https://doi.org/10.3389/fcell.2021.78942. Graphics reproduced from journal and modified by Gaussling.

In general, if you can change the shape of a molecule, particularly with peptide or nucleotide polymer molecules, you will change the physical properties and the reactivity properties. The Psi nucleotide adds another hydrogen bonding group into the mRNA. These changes add up to lowering the immune response to the vaccine.

The other noteworthy aspect is the very short time it took to get vaccines on the market. This was only possible because decades of research in molecular biology continuously advanced the state of the art. The various funding agencies whose support of basic research over the long haul deserve thanks as well for the timely production of the COVID-19 mRNA vaccine.

ExxonMobil Evolving with Declining Gasoline and Diesel Demand

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An article by Kevin Crowley, Bloomberg News, 9/23/23, reports that ExxonMobil Corp. has already begun to adapt to the decline in demand for gasoline and diesel as the switch to electric vehicles and renewable energy progresses. ExxonMobil operates the largest oil refining network in the world with 13 refineries presently in operation. It sold 5 refineries in the last 4 years in order to focus on cost cutting and improvements in performance of the highest performing facilities. ExxonMobil’s interest in refining dates back to the early days of its progenitor, Standard Oil Company, founded by John D. Rockefeller.

The oil majors are not blind and deaf to the swing towards the replacement of gasoline and diesel powered vehicles. In the case of ExxonMobil, they are planning on switching to production of petrochemical feedstocks in their refineries. They expect that their high-performance chemicals will see 7 % growth per year. Exxon believes the key to its success will be in chemical products. These chemicals are used in manufacturing of industrial and consumer products, from lubricants to pharmaceutical raw materials. Many of the ingredients you see in consumer products have their beginning as crude oil flowing out of the ground somewhere.

A Second Edition Organic Chemistry Textbook

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On occasion I step off the industrial hamster wheel for a few minutes to have a look around. In Linkedin this morning I saw a post for the 2nd edition of Organic Chemistry by Jonathan Clayden (Author), Nick Greeves (Author), Stuart Warren (Author), Oxford University Press, ISBN-13 ‏ : ‎ 978-0199270293. From inside the hole along the creek where I spend my free time, I was never aware that Warren had an O-chem textbook.

Amazon allows you to examine a bit of content on-line. If you teach O-chem, this text is worth a look in my estimation.

Many of us are familiar with Warren from his book Organic Synthesis: The Disconnection Approach, 1st edition 1982. A second edition was released in 2008. Retrosynthesis was spreading around to the far-flung corners of the chemistry polygon then. Warren’s book was quite useful in demonstrating that technique for devising an organic synthesis.

An interesting interview of Warren can be found at The Skeptical Chymist from 2009. Warren died in 2021 at age 81.

Chemical Emergencies and Safety Data Sheets in Education

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Note: Below is a quick safety brain-dump from a career in academic chemistry labs and chemical manufacturing facilities. It is not meant to be an unabridged guide to lab safety. Look elsewhere for that. it is easy to overlook Safety Data Sheets that come with chemical purchases.

At some time in their chemistry education the student should have had a good look at the chemical Safety Data Sheet or SDS for the chemicals and solvents they are using. While not necessarily very informative in terms of reaction chemistry, these documents are taken very seriously by many groups who can/will have an impact on your chemistry career and safety. Regardless of your walking-around-knowledge about a chemical substance, you should understand that the people who respond to emergency calls for a chemical incident will place a high reliance on what is disclosed on an SDS. A student who is connected with an incident won’t be the first point of contact when the fire department or ambulance arrives and wants information. In fact, it is highly unlikely that a student will ever have direct contact with a responder unless it is with an EMT.

Know where the SDS folder is. It may be in print or online.

When emergency responders arrive at the scene of your chemical incident, they will have protocols built into a strict chain of command. All information will pass through the responder’s single point of contact. The fire fighter with the fire hose is not the person you should try to communicate with. Information regarding the incident must be communicated up the chain of command from your site incident commander. The person responsible for the lab should know who that is. The staff at the incident site (your college) will also have protocols built onto a chain of command. Again, “ideally” the incident commander at the incident site will ask for information from others on the site regarding details on the event including the headcount (!) and communicate it to the incident commander of the responders. This is done to avoid confusing the responders with contradictory or useless information. Do not flood the responders with extraneous information. Don’t speak in jargon. If there are important points like “it’s a potassium fire”, pass it along. If there are special hazards like compressed hydrogen cylinders present, they’d like to know that too. Answer their questions then step back and let them do their job.

When responders arrive at the scene of a chemical incident, the first question they will ask is if everyone is accounted for. If everyone is accounted for, they will not risk their lives in the emergency response. However, if there are people unaccounted for or known to be trapped in a dangerous place or incapacitated, the responders will take greater chances with their own safety to rescue the victims. They will act to minimize property damage only if it can be done without risk to life and limb. Nobody wants to die saving property.

College chemistry departments that I have been involved with have had a flat policy of evacuating everyone from the building and congregating them at a defined location in response to an alarm. That way there is at least some reasonable chance that an accurate head count can be made. If technical advice is needed, faculty connected with the incident site should be consulted. The college will have an Environmental Health and Safety (EH&S) group or person who presumably will take charge of the incident on the incident side. The leader of EH&S should be informed of any hazards unique to the substance of concern if there is no SDS. Let them communicate with the responders. Generally, we chemists help most when we keep out of the way.

College chemistry departments are famous for housing one-of-a-kind chemical substances in poorly labeled bottles in faculty labs. These substances almost never have any kind of safety information other than perhaps cautionary advice like “don’t get it in your eye.” Luckily, university research typically uses small quantities of most substances except perhaps for solvents. Solvents can easily be present at multiples of 20 liters. These large cans are properly kept in a flammables cabinet. While research quantities may not represent a large fire hazard initially, there could easily be enough to poison someone. When you get to the hospital, the ER folks will have to figure out what to do with your sorry ass lying there poisoned by your own one-of-a-kind hazardous material.

In principle, the professor in charge of a chemistry research lab should be responsible for keeping an inventory of all chemicals including research substances sitting on the shelf. Purchased chemicals always have an SDS shipped with them. These documents should be filed in a well-known location and available to EH&S and responders.

The chemistry stockroom is a special location. Chemicals are commonly present at what an academic might call “bulk” scale, namely 100 to 1000 grams for solids and numerous 20 L solvent cans. The number of kg of combustibles and flammables per square meter of floor space is higher here. The stockroom manager should have a collection of SDS documents on file available to responders.

Right or wrong, people positively correlate the degree of hazard to the nastiness of an odor. Emergency responders are no different. This is another reason why it is critical for them to have an SDS. People need to adjust their risk exposure to the hazard present as defined by an SDS. We all know that some substances that are bad actors actually have an odor that is not unpleasant for a short time, like phosgene. Regardless of this imperfect correlation, if you can smell it, you are getting it in you and this is to be avoided. Inhalation is an important route of exposure.

In grad school we had an incident where a grad student dropped a bottle in a stairwell (!) with a few grams of a transition group metal complex having a cyclooctadiene (COD) ligand on it. Enough COD was released into the stairwell to badly stink it up. They didn’t know if it was an actual chemical hazard or not, so they pulled the fire alarm handle. The Hazardous Material wagon showed up right next to 50-60 chemistry professors, postdocs, and grad students. The responders were told what happened and with what, so they dutifully tried to find information on the hazards in their many manuals. They did not find anything.

They had 50-60 chemists within spitting distance but didn’t ask us any questions. This is because they are trained to respond as they did. This was a one-off research sample of a few grams but it had an obnoxious smell with unknown hazards. Finally they sent in some guys in SCBA gear and swept up the several grams of substance and set up a fan for ventilation. Don’t be surprised if the responders don’t have special tricks up their sleeves for your chemical event. They can’t anticipate every kind of chemical incident.

HazMat Team. Credit: https://en.wikipedia.org/wiki/Hazardous_materials_apparatus

Long story short, both the responders and the chemists didn’t have any special techniques tailor made for this substance. There was not evident pyrophoricity or gas generation. It was a dry sample so no flammable liquids to contend with. The responders used maximum PPE and practiced good chemical hygiene in the small clean up. Case closed.

An SDS is required for shippers as well. It shows them how to placard their vehicles according to the hazards. Emergency responders need to see the SDS in order to safely respond to an overturned 18-wheeler in the road or to a spill on a loading dock. It could also be that the captain of container ship wants to know precisely what kind of hazardous materials are visiting his/her ship.

Finally, an SDS should be written by a professional trained to do it properly. By properly I mean by someone who understands enough about regulatory toxicology, emergency response, relevant physicochemical properties, hazard and precautionary statements and shipping regulations to provide responders with enough information to respond to an incident. Here, incident means an unexpected release with possible exposure to people, a release into the environment or a fire or possible explosion.

In my world, the word “accident” isn’t used so much anymore. With the advent process hazard analysis (PHA) required by OSHA under Process Safety Management prior to the startup of a process, potential hazards and dangers are anticipated by a group of experienced experts and adjusted for. So, it is getting harder to have an unexpected event. “Accident” is being replaced with the word “incident.”

Toxicology is a specialty concerned with poisons. Regulatory toxicology refers to the field where measurements and models are used to define where a substances belongs in the many layers of applicable regulations. Toxicity is manifested in many ways with many consequences and each way is categorized into levels of severity. There is acute toxicity and there is chronic toxicity. Know the difference. That said, dose and exposure are two different things. Exposure relates to the presence of external toxicants, i.e., ppm in water or micrograms per cubic meter of air. Dose relates to the amount of toxicant entering the body based on the exposure time in the presence of a toxicant and the route of entry.

An SDS uses signal words like “Caution”, Warning”, or “Danger”. A particular standard test is needed to narrow down the type and magnitude of the toxicity. The figure below from the GHS shows the thresholds for categorization of Acute Toxicity.

Credit: Globally Harmonized System of Classification and Labeling of Chemicals.

Hazard and precautionary statements are important for an SDS. Rather than having everybody dreaming up their own hazard descriptions and precautions, this has been standardized into agreed upon language. Among other sources, Sigma-Aldrich has a handy list of Hazard Statements and Precautionary Statements available online.

Regulatory toxicology is very much a quantitative science enmeshed with a web of regulations. The EPA for instance does modeling of human health and environmental risks based on quantitative exposure or release inputs. Without toxicological and industrial hygiene testing data, they may fall back on model substances and default, worst case inputs to their models. In reality the certain hazard warnings you see on an SDS may or may not be based on actual measurement. The EPA can require that certain hazard statements be put on a given SDS based on their assessment of risk using models or actual data.

To be clear, hazard information reported on an SDS are considered gospel to emergency responders. Chemists of all stripes should be conversant with Safety Data Sheets and have a look at them the next time a chemical arrives. Your lab or facility should have a central location for SDS documents, paper or electronic.

In the handling and storage of chemicals, some thought should be given as to how a non-chemist would deal with a chemical spill. Is the container labeled with a CAS number or a proper name rather than just a structure? A proper name or CAS # could lead someone to an SDS. Is there an HMIS or other hazard warning label? There are many tens of thousands of substances that are either a clear, colorless or amber liquid or a colorless solid. If not for the sake of emergency responders then for the poor sods in EH&S who will likely have to dispose of the stuff when you are long gone. Storing chemicals, liquids especially, with some kind of secondary containment is always a plus. Keep the number of kilograms of combustibles and flammables in the lab to a minimum. A localized fire is better than a fire that quickly spreads to the clutter on the benchtop or the floor.

The Refinery Crack Spread

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Reuters has reported that the crack spread enjoyed by oil refiners is currently sitting around $37.50. The crack spread is the difference between the price of crude oil and the petroleum products coming from it. This number is an indicator of the profitability of refinery output.

Cracking is a major operation at oil refineries where heavy, long chain hydrocarbons are broken into shorter chain hydrocarbons. Crude oil naturally contains a limited amount of components suitable for modern engines. An important attribute is branching. The goal is to produce the most valuable products from otherwise longer chain, lower value hydrocarbons.

A Scratch in the Surface of Gas Chromatography

The analytical workhorse of the petroleum refinery is the gas chromatograph, or GC. The GC consists of a precisely controlled oven and within it is a coiled, small diameter hollow fiber many meters in length. It is called a capillary GC column. At one end of the column is an injection chamber with a silicone septum that samples are injected through via syringe. This chamber is hot enough to flash evaporate the sample but not so high that it decomposes. For instance, I have usually used a 250 oC injector temperature. A common volume of liquid to be injected is 1 microliter. The sample can be neat or a solution and must be scrupulously free of particles.

Inside the injector is the carrier gas input- helium is often used. A large amount of the vaporized sample is flushed out of the injector leaving only a small quantity of sample to be injected. Connected to the injector is the entrance of the capillary column. The goal is to inject a very narrow plug of sample into the capillary column all at once. After the injection, the detector is activated and the data collection begins. Progress can be followed in real time or not. Once the sample is on the column the GC run must be taken to completion. There is no reset for the column.

Capillary column. Source: Agilent.

The inside surface of the long capillary column can be just fused silica or it can have a coating. In any case, the components of the sample each have a different affinity for the inner wall of the capillary. As the carrier gas pushes the vaporized sample components along, the components with the least affinity for the inner column surface advance through the column fastest and arrive at the detector earlier. Generally, the higher the molecular weight, the lower the volatility and the longer it takes to exit the column.

At the terminus of the capillary column is the detector. There are a variety of methods used to detect sample and send a signal to the plotter or computer. A particularly useful type of GC system uses a mass spectrometer as a detector. The flow of components enters an ionization chamber and positive ions are generated by electron impact and sent through the mass analyzer and on to the detector. This is occurring continuously as the sample components exit the column. As the components are detected, a regular chromatogram is collected and displayed. The difference with the mass spec detector is that along the timeline, mass spectra are also collected. It is possible to select any given peak in the chromatogram and display the mass spectrum.

A mass spectrum for every peak. Source: God I hope they don’t mind my using this graphic. American Chemical Society. I don’t need ACS goons banging on my door again!
Graphic from NASA showing schematic of the GC Mass Spec aboard the Huygens probe to Titan.

A mass spectrum detector offers the possibility of identifying the individual peaks from the molecular ion mass and the fragmentation pattern. That said, not all mass spectra are easily interpreted. Only cation fragments are visible. Neutral fragments must be inferred.

A stack of gas chromatograms showing the components of crude oil and several derived products below it. Each peak indicates a single component with the intensity along the y-axis and time in minutes along the x-axis. The area under each peak is proportional to the % composition in the sample. On the left side of the chromatogram are the components that are more volatile and exit the GC column earliest. The right side shows the components that exited the column after longer intervals. They are the longer chain molecules. Source: IRTC.

Back to the Crack

The most valuable refinery products are gasoline, fuel oil (including diesel), and aviation fuel. Within these three areas are subcategories that split into different product lines. These fuel product categories are defined by the number of carbon atoms in the blend of hydrocarbon molecules, saturation, and branching.

Refineries produce blended fuels affording certain properties according to their use. These properties include boiling point and vapor pressure specifications, octane or cetane numbers, viscosity, and pour point specifications. Between distillation, cracking, aromatization and reforming a wide variety of hydrocarbon substances are available from refining for formulation. A refinery is engineered to produce the largest volume of the most valuable hydrocarbons from continuous flow processes at the greatest profit.

Oh, I was just joking about the ACS goons. They don’t bang on your door.