Industrial Alchemy: Part 3, Organic Chemistry Methods and Canonical Appearances

Organic Chemistry is both a new discipline, and an old one. New, in that the first artificial synthesis of an organic compound didn’t occur until 1828. Old, in that organic compounds, in dilute form, have been produced for centuries: ethyl alcohol and acetic acid (vinegar) by the beer and wine industry; fatty acid salts by the soap industry; dyestuffs by the dyers, and various pharmaceuticals in the extracts of the herbalists.

“Grantville Literature” on Organic Chemistry

There are probably at least a score of copies of the CRC Handbook of Chemistry and Physics in Grantville. And they probably represent nearly as many different editions. To give the reader an idea just how useful the “CRC” is, the organic chemistry specific data in the 70th edition (1989-90) includes

—Physical Constants of Organic Compounds: molecular formula, molecular weight, color, crystalline form, specific rotation, lambda-max, boiling and melting points, density, refractive index, and solubility.

—structural formulae for the tabulated organic compounds

—indexes to those same compounds, ordering them by melting point, boiling point, or molecular formula.

and much more.

There is a fairly good chance of finding Lange’s Handbook of Chemistry in Grantville. Some of the information provided is similar to that in CRC, but there is more chemical content, such as specific tables concerning “fats, oils and waxes,” and “petroleum products”.

The pharmacists will have several editions of The Merck Index (MI). It provides structures and activities for thousands of pharmaceuticals and intermediates, and final synthetic steps for some of them. Most editions (not 11th!) have a section describing “Organic Name Reactions” which is a nice supplement to the basic organic chemistry texts.

Any one who holds a chemistry degree is guaranteed to have taken introductory organic chemistry (usually as a sophomore), and it is almost certain that however long ago he or she graduated college, that organic chemistry textbook is still around the house or office somewhere.

Figuring out which organic chemistry textbooks are most likely to be present in Grantville is a little trickier. As a criterion, I looked at how many OCLC libraries had a copy of any edition of a basic organic chem textbook for which there was an edition published in 1998 or 1999. The clear winners were (1) Morrison and Boyd, 4th ed,1998; (2) Solomons, 7th ed,1999; and (3) McMurray, 5th ed, 1999. (Here, all M&B references are to the 1966 edition, and Solomons, to the 1992 or 1996 editions.)

A chemistry major is likely to have a copy of the Condensed Chemical Dictionary (CCD). For quite a few compounds, it has a “derivation” section that explains the final step in synthesizing that compound. You can work your way backward.

Besides the familiar encyclopedias, the Grantville high school, like its Mannington counterpart, has the fifteen volume McGraw-Hill Encyclopedia of Science and Technology (1977)(McGHEST).

Unavoidable Organic Chemical Nomenclature

Organic chemistry can be considered the study of hydrocarbons and their derivatives. Hydrocarbons are compounds consisting solely of carbon and hydrogen; in a derivative, one or more hydrogens is replaced by a new atom or atoms (at least one being something other than carbon or hydrogen).

Forget derivatives for now. Hydrocarbons can be grouped into several broad classes depending on how their carbon atoms are connected.

One classification is based on the topology of the “carbon skeleton” (the chain, or chains, of carbon atoms which are bonded together):

linear
branched
cyclic (contains one or more rings, fused or unfused)
.. carbocylic (all atoms carbon)
.. heterocylic (includes non-carbon atom)

The number of carbon atoms may be indicated, e.g., C1 (methane), C2 (ethane, ethylene and acetylene), etc. The carbon skeleton may be discontinuous in which case the compound will have some linking group (typically -O-, -S- or -NH-) which connects the carbon chains. In ethers and esters, it’s -O-.

Another classification is based on the nature of the bonds. If a compound has both single and double bonds (not necessarily carbon-carbon) in the right arrangement, electron delocalization can occur, which stabilizes the molecule. An aromatic compound is one in which electron delocalization occurs over a ring, such as the benzene ring.

All hydrocarbons which aren’t aromatic are “aliphatic,” these are classified as follows:

alkanes (paraffins; saturated): just single strength (C-C) bonds
alkenes (olefins): at least one double strength (C=C) bonds, nothing stronger
alkynes: at least one triple strength (C=C) bond
(alkenes and alkynes are also called “unsaturated” because you can add hydrogen to them)

“Functional groups” are clumps of one or more atoms which impart some reactivity not possessed by an alkane. For a long list, see http://en.wikipedia.org/wiki/Functional_groups. Derivatives have one or more functional groups not found in hydrocarbons. Such functional groups can be side chains, or they can link one hydrocarbon moiety to another.

Organic chemical synthesis can be thought of as the manipulation of the carbon skeleton and the attached functional groups of the various reactants.

Natural Feedstocks

The starting points for the organic chemical industry are natural “feedstocks,” that is, natural sources, usually complex mixtures, of organic chemicals. These fall into three major categories: coal, petroleum/natural gas, and biomass, which we will discuss in some detail in part 4. The same chemical, of course, may be available from feedstocks of different types.

All organic chemicals contain carbon, which means that all organic compounds have an energy value—they can be burnt, generating carbon oxide and releasing energy. That means that all of the feedstocks are at least potentially subject to competing demands for organic chemicals and for fuel. That is particularly true of coal, petroleum, natural gas, and wood. Wood, of course, additionally is in demand as a structural material.

In the twentieth century, the organic chemical industry could compete with the energy industry for use of the same starting materials because it could charge a lot more by weight for its products.

Organic Chemical Operations

The product of one organic chemical process can be the feedstock for another. Thus, organic chemical operations fall into two categories: those which process a natural feedstock, usually a crude mixture of a multitude of chemicals, and those which start with a pure chemical (or at least a relatively simple mixture) and convert it into another chemical.

The crude feedstock probably contains chemicals which vary in economic value and the facility may be designed to process one of those chemicals and discard the rest. For example, the first petroleum refineries extracted kerosene and dumped everything else. That, of course, not only means that no economic value is realized from the waste chemicals, it also results in pollution.

Other facilities are designed to separate the mixture and process each of several components for ultimate use or sale. The coal gas plant in Magdeburg (Flint, 1634: The Baltic War, Chapter 2) is in that category, since it produces ammonium nitrate, illuminating gas, light benzoil, and pitch.

In theory, the methods used to separate the feedstock chemicals would not change them in any way. In practice, if the distillation temperature is high enough, some chemicals will decompose, altering the “mix” which is fractionated. That’s an unavoidable consequence of the pyrolysis (destructive distillation) of coal. And chemists will sometimes voluntarily do things during the refining process which will modify the low-value chemicals into high-value ones.

Organic Synthesis

It is not uncommon for a chemical to initially be supplied as a natural product. As the natural sources are depleted, the incentive to duplicate it synthetically increases.

Synthetic chemicals may be simply duplicates of naturally occurring products (e.g., alizarin, a dye originally extracted from the madder root, or indigo) or a non-naturally occurring analogue (as aspirin, acetylsalicylic acid, was of salicylic acid). Often, these analogues are “semi-synthetic”; that is, synthesized, in a small number of steps, from the natural product whose activity they mimic. This may be a matter of necessity, if the total synthesis of the natural product hasn’t been achieved.

In the strictest sense, total synthesis is the non-biological synthesis of an organic chemical, by one or more steps, from inorganic precursors. The term is informally used to refer to synthesis from the primary chemicals isolated from coal and petroleum feedstocks (but not from fermentation products). Of course, as the chemical industry makes more chemicals commercially available, it will be less common to synthesize new ones completely from scratch.

The bare minimum of information needed for the synthesis of an organic compound is knowledge of its complete structure. Usually that will be conveyed by a structural formula, or a systematic chemical name. Those are usually found either in a chemistry textbook, or in a reference work (CRC; MI).

The next step up is a schematic synthesis, specifying the reactants and products for one or more synthetic steps. A standard organic chemistry text might set forth several hundred synthetic steps. You might find a complete synthesis for the compound of interest, or just a relevant step or two (and you then have to fill in the gaps).

Best of all is a synthesis protocol. By way of example, M&B757 just says that acetanilide can be reacted with chlorosulfonic acid to make p-acetamidobenzenesulfonyl chloride (this is the second step in the disclosed synthesis of the antibiotic sulfonilamide). In contrast, the lab-oriented Lehman, Operational Organic Chemistry (395-6) devotes two pages to that one step.

If all you have is a structure, then you have to devise the synthesis yourself, relying on general principles. It is best to work backwards from the desired product, “disconnecting” it into fragments which are likely to be manipulable by standard steps, and then figuring out which reactants would introduce the needed fragments in the desired way. It is a bit like solving a jigsaw puzzle . . . when you are given the pieces for several different puzzles simultaneously.

When you plan a synthesis, you take a close look at the carbon skeleton. The standard synthetic steps typically are either (1) changing the carbon skeleton (adding or removing carbons, opening or closing a ring, or saturating or desaturating carbon-carbon bonds), or (2) adding, eliminating or replacing one or more non-hydrocarbon substituents.

These steps take advantage of the functional groups present in the reactants. A functional group is an atom, or group of atoms, which gives the compound a characteristic chemical reactivity. The major classes of hydrocarbon derivatives are classified according to the functional groups which they contain. For example, amines contain NH2; alcohols, hydroxyl (OH); aldehydes and ketones, carbonyl (>C=O); and so on.

A single compound can have more than one functional group, which can be the same or different. Sometimes they act independently, and other times (especially when close to each other) they interact, changing each other’s reactivity. So, if you are synthesizing a compound with several functional groups, you have to worry about those interactions. The order in which you add functional groups can make a big difference.

If the skeleton we need isn’t available from a natural feedstock, we build it. One of the neater tricks converts a Grignard Reagent (see below) into an alcohol with one additional carbon. (A different reaction turns it, similarly, into a longer carboxylic acid.) Many schemes of adding and subtracting carbons exist, but they have their limitations. (Payne, 11-20).

You have to exercise a certain amount of caution about reliance on “standard steps.” You may know that a compound of class A reacts with a compound of class B. But depending on the specific compounds involved, one reaction may work fine at room temperature, and another might need heat or a catalyst, or an equilibrium-shifting trick (see Part 1, Inorganics).

You may also need to use an indirect approach. This can involve use of a special synthesis intermediate (see below), in essence, a compound of a type known for the ease in which it can be converted into many other compounds.

Even without resort to the special intermediates, you may find it best to have an intervening step. For example, instead of aminating (introducing NH2 into) a benzene directly with ammonia, you would more likely nitrate it (introduce NO2 into it) first, and then reduce the nitrate group to the desired amino group. That’s two steps, rather than one, but the yield will be a lot higher.

The indirect approach may also be necessary when you are trying to synthesize a polyfunctional compound. The reagent intended to add the second functionality may damage the one already on the molecule. The solution is to protect the first functionality, add the second, then deprotect the first one. That’s done in, for example, the standard synthesis of the antibiotic chloramphenicol.

All else being equal, it’s best to minimize the steps. Even if the yield of each step is 90%, six such steps means the overall yield is only 53%. Also consider atom economy; how many of the atoms in the reactants are unused in the desired product(s)? And to keep costs down, when possible add the most expensive reactants last.

Linear synthesis involves forming each intermediate from the one before. In convergent synthesis, large fragments are synthesized independently, then combined at the end; this usually results in fewer steps and higher yields.

It’s worth noting that there was a revolution a few decades ago in the teaching of organic chemistry. Early textbooks were organized according to the structure of the compound, and stated the principal preparative methods and characteristic reactions of each functional groups. The modern approach is to emphasize the mechanism that underlies the reactions. There is probably a steeper learning curve to actually making new compounds with the modern approach, but it allows one to make more educated guesses about how some new structure will behave than did the old method.

Special Synthesis Intermediates

These are highly reactive materials that can be converted into a wide variety of organic compounds.

Synthesis Gas

Synthesis Gas is a mixture of carbon monoxide and hydrogen. The principal commercial method of making methanol uses synthesis gas. But its versatility was best demonstrated by the Fischer-Tropsch process, which was essentially a polymerization reaction (using a metal oxide catalyst), creating a large variety of aliphatic hydrocarbons (EA). It was developed to solve Germany’s fuel crisis of the Twenties.

Synthesis gas can be produced from pretty much any hydrocarbon source (including natural gas, petroleum, coal, and biomass) If you heat coal in the presence of lots of air, the oxygen converts it all to carbon dioxide. That’s ordinary combustion. If you heat it in the absence of air, you get destructive distillation to coal gas and coke. To make synthesis gas, you want incomplete combustion. You heat the coal with steam (H2O) in the presence of a little bit of air. When this process is properly adjusted, the reactions which take place result in production of hydrogen, carbon monoxide, and only a trifling amount of carbon dioxide. This reaction is actually alluded to in EB11/Fuel, in the discussion of “blue water gas,” which was first made in 1780 by Felice Fontana.

Acetylene

Acetylene (HC=CH) is one of the most important potential carbichemicals. In World War I, Germany used acetylene in the production of a rather inferior synthetic rubber (“methyl rubber”). History somewhat repeated itself in World War II, when acetylene was used by Germany in the production of ethylene and butadiene (for a better synthetic rubber), Acetylene has also been used to produce vinyl choloride, vinyl acetate, vinyl fluoride, acrylonitrile, acetaldehyde, and trichloroethylene. (KO 1:195; Wittcoff 112). It’s also the fuel of the oxyacetylene torch.

Unlike most carbichemicals, acetylene is derived from coke, not coal tar. In 1892, it was discovered that lime (calcium oxide) and coke could be cooked together at 2000 °C in an electric arc furnace (ordinary combustion doesn’t generate a high enough temperature) to produce calcium carbide, which in turn was reacted with water to form acetylene (M&B 239; EB11/Acetylene).

Calcium carbide production is a bit problematic. First of all, you need lots of cheap electricity, preferably near coal mines. Grantville is one possibility, Lyons might eventually be another. The reactants and product are solids, which makes them difficult to handle. And they are also corrosive, so don’t expect the reactor to have a long working life. (Wittcoff 111).

A more modern route to acetylene involves high temperature (1500 °C) controlled oxidation of methane from natural gas or petroleum. (M&B 240). I think that the high temperature and the necessary process controls make this method unattractive for the foreseeable future.

Acetylene is tricky stuff to handle; for storage, pressurized acetylene is introduced into a cylinder filled with a porous material soaked with acetone. It is probably wise to transport it only short distances, and use it promptly.

Alkyl Halides

In modern industry, alkyl halides are made by high-temperature halogenation of alkanes. In the laboratory, they are more likely to be made from alcohols or carboxylic acids (thionyl chloride needed, available perhaps in 1635), or occasionally from alkenes or alkynes.

Alkyl halides (usually chlorides) can be converted, in a single step reaction, into nitrile, alcohol, thiol, ester, ether, thioether, hydride, and other derivatives by displacement of the halogen. They can also be converted into alkanes and alkenes, and into an even more useful intermediate called a Grignard reagent.

Grignard Reagents

To make a Grignard reagent, you react an alkyl halide with metallic magnesium. The Grignard reagent is extremely reactive, so it is generated for immediate use. But because of that reactivity, it can be used to make derivatives which can’t be prepared directly from an alkyl halide.

Diazonium Salts

To make a diazonium salt, you need an aromatic amine, sodium nitrite, and a hydrogen halide. Diazonium salts allow you to make many different derivatives of aromatic compounds. These derivatives include some important dyes, such as Congo Red, Trypan Blue, and tartrazine.

Protective Groups

As our chemists attempt synthesis of complex compounds, with multiple functional groups, they will find that they have difficulty limiting the reaction to the site they wish to affect. They may inadvertently add a functionality somewhere it isn’t wanted, or even degrade the intermediate they are working with. The standard solution to this problem is to selectively protect and later deprotect the sensitive functional group. Chemists have developed standard protecting group chemistries for hydroxyl, amine, carbonyl, and other common moieties. McGHEST/Organic Synthesis has a useful discussion.

Enzymes

Enzymes (biocatalysts) can be found in microorganisms, plants and animals, and isolated enzymes can be used to carry out very complex transformations in a few steps, and with stereospecificity. Rennet (chymosin) was the first (OTL 1874) enzyme purified (from calf stomachs) for industrial use. Pancreatic proteases were used to bate hides (1907), degum raw silk, and prewash clothes, and papain to stabilize beer (1911). (Uhlig 6ff).

Trading with tropical colonies will give us access to pineapple and papaya, and thus to the proteases bromelain and papain. Bacteria and fungi are rich sources of other enzymes.

Separation

In order to make use of complex natural feedstocks, you have to separate the mixture into the component chemicals, or at least into fractions of sufficiently consistent physical and chemical properties so that they form a salable product.

If you conduct a chemical synthesis, you have to separate the desired product from the solvent, any excess reactants, and any byproducts. The most important organic chemical separation methods are distillation, extraction and recrystallization.

Distillation

This relies on the difference in the volatility (the tendency to pass from the liquid to the gaseous state), at the distillation temperature, of the components. In general, this is closely related to the boiling point; the lower boiling components tend to be concentrated in the vapor. But it is good to realize that it isn’t an all or nothing situation; there will be some vaporization of a compound before its boiling point is reached.

For distillation, you need a heat source (usually operating on a heating bath), a pot (in which the liquid mixture is boiled), a head (through which the vapor rises), a condenser (in which the vapor is condensed back to a liquid), and a receiver (in which the liquid is stored). The heat source is usually outside the pot. However, in steam distillation, steam is bubbled through the mixture.

When Grantville popped out of nowhere, the alchemists had been distilling chemicals for centuries. Hieronymous Braunschweig wrote The Art of Distillation in 1500. The big distillation breakthrough of the early-seventeenth century was the continuously water-cooled, counter-flow worm (Graham) condenser. (McCuster, 195). This is a spiral pipe (carrying the vapor) which is run through a large reservoir (holding liquid coolant). Or the vapor and the coolant can be reversed.

Stoner taught the Venetian glassmakers how to make a Liebig condenser (invented by Wiegel in 1771), which is a simple vapor tube running through a concentric outer coolant tube with a coolant inlet and outlet. “When I drew a Liebig condenser for them, there were a few guys slapping foreheads, and a couple of the glassware shops did a roaring trade in the things for a couple of weeks. They use copper pipes and leather fittings, but they work.” (Flint and Dennis, 1634: The Galileo Affair, Chapter 33).

Dry distillation. Solid materials could be heated at high temperatures so they were converted directly into gases. The operation was known in classical times, and alchemists used it to produce several organic compounds.

Fractional distillation. When some components have similar boiling points (less than 25 °C apart), you need to conduct repeated vaporization-condensation cycles, so that there is a gradual enrichment in favor of the lower boiling component. This is achieved by elongating the simple distillation head into a fractionating column. The column has trays or a packing material on which vapor can condense, and from which it can vaporize again as it gets heated by rising vapor. The column may be designed so that the condensate can be withdrawn from different heights in the column.

It appears that in the thirteenth century Taddeo Alderotti concentrated alcohol by means of a crude fractional distillation apparatus with a single withdrawal point. However, it was not a commonly used technique. (Holmyard 53ff).

There is no free lunch. While fractional distillation can separate more similar compounds, the distillation apparatus is more expensive (especially on an industrial scale), and the distillation takes longer and requires more energy to keep re-evaporating the liquid. The separation power depends on the structure of the column, but I think a good rule of thumb would be that our heroes can achieve a useful separation if there is more than a 6 °C boiling point difference.

Freeze Distillation. Instead of separating compounds on the basis of the difference in their boiling points, you can exploit differences in melting points, cooling the mixture to an intermediate temperature and separating the frozen material from that still liquid. If you then melt and refreeze the frozen material, you have fractional freezing.

Freeze distillation was used in medieval Central Asia to concentrate ethyl alcohol, but this “frozen-out wine” has the problem (from a drinkers’ standpoint) that it also concentrates the other, poisonous alcohols. For the new organic chemical industry, that might be an advantage.

Vacuum distillation. A general problem with distillation is that the high temperatures can cause some compounds to decompose. This can be avoided by vacuum distillation; if pressure is reduced, the boiling points are lowered. Vacuum distillation was not known down-time.

Extraction.

Liquid-liquid extraction takes advantage of differences in the relative solubility of the components in two immiscible liquids. The important characteristics of the extractive solvent are its selectivity (preference for the desired component), capacity (the solubility of the component in it), toxicity, corrosiveness, liquid temperature range, availability, and price. It also has to be quite pure.

The alchemists macerated a variety of botanical extracts; the catch was that they had only a limited choice of solvents, and their extracts were primarily with water or alcohol, or mixtures of the two. Perfumers placed botanicals on animal fat, allowed the fragrance chemicals to diffuse into the fat, and then extracted them from the fat with alcohol (enfleurage).

Ethers, chloroform, and carbon disulfide or tetrachloride have very different solvent properties (Rydberg 28) and their availability would revolutionize extraction technology.

Crystallization.

Crystallization takes advantage of differences in solubility. It was known to the alchemists; Biringuccio used it to purify saltpeter. (Feigelson 1).

In fractional recrystallization, the crystals are redissolved and then recrystallized, thereby losing residual impurities.

Synthetic Isomer Separation

Some organic chemical reactions result in isomerization. One variety occurs when the reagent has more than one point of attack on the starting material. If, in some starting material molecules, it adds a group to an end carbon, and in other molecules, to the penultimate carbon, then you end up with a mixture of molecules with different structural formulae, that is, different bond connections. Those are called “structural isomers.”

The standard synthesis for DDT produces not only the desired p,p-isomer, but also ones in which one or both chlorines end up in the wrong position relative to the ethane bridge (o,p- and o,o-isomers). The three isomers all have pesticidal activity, but the p,p-isomer is several times more active than the others.

Sometimes, a compound’s three-dimensional structure will be such that an atom can be approached from distinctly different “sides.” If so, then the reaction may result in a functional group being linked to that atom on one side in some molecules and on the other side in others. Two compounds with different 3-D structures result, which are considered “stereoisomers” of each other, and the “two-sided” atom is called a stereogenic center. This is important because if a pharmaceutical has stereoisomers, it is not uncommon that one is active and the other isn’t.

It is worth noting that a drug might have more than one stereogenic center, hence more than two stereoisomers. That’s a concern with chloramphenicol, which has two centers and thus four stereoisomers.

The chemist has three choices for dealing with stereoisomers:

(1) just produce a “racemic mixture” of all the stereoisomers. It won’t be as active as the desired one, but it’s better than nothing (or the wrong one).

(2) produce the racemic mixture and then “resolve” it, that is, separate the stereoisomers (or reversible derivatives of them) based on some physical property (boiling point, melting point, solubility, etc.)

(3) use a stereochemically-specific reaction (“asymmetric chemistry”), that is, one which for some reason (perhaps the configuration of a catalyst) favors one stereoisomer over another.

In the case of chloramphenicol, the trick used in the Forties was to form the tartrate salts of one of the intermediates, and then separate them by fractional crystallization. More recently, asymmetric chemical pathways have been developed.

Characterization of Organic Compounds

There are several reasons why you may have to identify an organic compound. Perhaps you are trying to isolate or synthesize a particular compound. If so, you need to know whether you have succeeded. Or perhaps you isolated the biologically active ingredient of, say, a plant oil, and you want to know what it is that you can design a synthesis for it. Or you have separated a natural feedstock into its components and you want to know what they are.

Elemental analysis tells you which atoms are present (qualitative analysis) and more preferably in what proportions (quantitative analysis) in the compound. Morrison and Boyd describe methods of assaying carbon, hydrogen, halogen, nitrogen and sulfur.

It is also important to determine the molecular weight of the compound. If you know the molecular weight, and the elemental proportions (and the atomic weights of each element), you can write the molecular formula. For example, the molecular weight of glucose is 180.16 grams per mole, and the molecular formula is C6H12O6.

There are a number of methods of determining the molecular weight of a compound. If it is volatile (gaseous at room temperature), you can measure the volume occupied by a known weight of the gas at a known temperature and pressure. Otherwise, you can dissolve a known weight of the compound in a known weight of a solvent, and measure how much it reduces the freezing point (cryoscopic method) or increases the boiling point (ebullioscopic method), since the change is proportional to the concentration of the solute. A popular solvent for the cryoscopic method is camphor, one mole of solute in 100 grams of camphor lowers its freezing point by 39.7*C. The gold standard for determining molecular weights is mass spectrometry, which is not something I am expecting to be reinvented in the near future.

The molecular formula gives the number of atoms of each element, but not how the atoms are connected. Those connections are depicted in the structural formula.

Ideally, to determine the structure of a complete unknown, we would subject it to spectroscopic analysis. I don’t expect any form of spectroscopic study (see Appendix) to be feasible within the first decade after the Ring of Fire.

So what can we do? We are left with the laborious process of inferring structure from the compound’s physical and chemical properties. The physical properties (solubility, melting and boiling point, density, refractive index, and optical activity) are most likely to be diagnostic if we find that they match the values for a known compound (and there is voluminous data in CRC).

Chemical properties are also useful, but in general they just tell you the class of compound involved. For example, you are probably dealing with a primary or secondary alcohol, or perhaps an aldehyde, if adding the substance to a clear orange solution of chromic anhydride in aqueous sulfuric acid changes to an opaque blue-green. (M&B 544).

During the investigation of the mysterious illness at the 1634 senior class picnic, a lab analysis reveals that the beer the students were drinking was laced with methanol. Offord’s “Class of ’34” (Grantville Gazette 4). The question is, how was the analysis conducted with the limited post-Ring of Fire resources? My best guess is that they ran a distillation. and found that they had a fraction boiling off at the boiling point of methanol (64.5oC), which is less than the boiling point of water or of ethanol (78.3oC). And if that fraction satisfied the various chemical tests for alcohol, then the police could be fairly confident that methanol was present.

If that known compound is available (we may just have legacy data from the CRC), then we can mix a pure sample of the known compound with the purified unknown. If the “mixture” has the same melting and boiling points as that of the known compound, then we know that the added unknown is identical to the latter.

If there is no match or no reference, then we are more reliant on chemical analysis. What happens if the unknown is exposed to water, cold or hot sodium hydroxide, dilute hydrochloric acid, concentrated sulfuric acid, acetyl chloride, sodium, bromine or other reagents? The reactivity patterns will suggest that particular functional groups are present, but they are not likely to do so definitively, and they don’t prove where each such functional group is located.

So, we cheat. We degrade the compound into fragments, and analyze the fragments. If need be, we break the fragments down further. Sooner or later, we will find ourselves dealing with fragments which correspond to known fragments. We can then make an educated guess as to how the known fragments are connected. We design a synthesis based on the hypothetical structure, carry it out, and see if the properties of the synthesized compound match those of the original one.

For this to provide proof, we of course have to be able to devise a synthetic route which we are sure is reliable.

Commodity Organic Chemicals

In the late twentieth century, the highest volume organic chemicals were primarily those used as intermediates in the production of other chemicals, especially plastics, rather than for “end use” chemicals. I don’t know whether that will be true in the new time line and, if it is, whether plastics industry intermediates will have the same importance. At a guess, the dyestuffs, drugs and explosives industries will loom larger in the early post-Ring of Fire period. But I am sure that many of the organic chemicals which were “top” chemicals in the late-twentieth century will be important in the first post-Ring of Fire decade too.

There are 31 organic chemicals among the fifty top chemicals of the U.S. chemical industry of 1995 (C&EN), and I have looked at what the encyclopedias, and if need be, the standard organic chemistry textbook Morrison & Boyd, have to say about how they are used and produced.

The top forty organic chemicals fall into six structural groups, as shown in Table 3-1. MTBE, used just for anti-knock, is a chemical which will be in much less demand in the 1632 universe, at least until gasoline is plentiful. On the other hand, the antiseptic phenol will be in much greater demand, given the limited medicinal arsenal.

Table 3-1: Top Organic Chemicals (1995)

C skeleton

Chemical

Rank

Selected Uses (polymers italicized)

C1 aliphatic

Methanol

10

solvent, antifreeze, general intermediate

Formaldehyde

12

disinfectant; preservative; mfr. glues, bakelite & other plastics

Urea

6

fertilizer; nitrocellulose stab.; mfr. clathrates, UF resin

methyl chloride

37

methylation and chlorination agent; refrigerant, mfr. silicone

C2 aliphatic

Ethylene

1

general intermediate; mfr. polyethylene

Ethylene dichloride

4

solvent; mfr. vinyl chloride

Vinyl chloride

7

mfr. PVC

Ethylene oxide

14

mfr. ethylene glycol; sterilant

Ethylene glycol

18

antifreeze; mfr. polyester

Acetic acid

19

mfr. cellulose acetate, PVA, PET

(2+2)

vinyl acetate

24

mfr. PVA

C3 aliphatic

Propylene

2

general intermediate; mfr. polypropylene

Propylene oxide

21

mfr. propylene glycol; polyurethane

Acetone

26

solvent; mfr. bisphenol

acrylonitrile

24

mfr. polyacrylonitrile

isopropyl alcohol

34

solvent

propylene glycol

38

coolant, solvent

(3+1)

methyl methacrylate

36

mfr. polymethyl methacrylate

C4 aliphatic

butadiene

22

mfr. synthetic rubber

isobutylene

23

mfr. MTBE, isooctane, methacrolein, butyl rubber

butyraldehyde

27

intermediate

1-butanol

33

solvent, intermediate

(1+4)

MTBE*

3

anti-knock (*methyl tert-butyl ether)

C6 aliphatic

cyclohexane

28

mfr. adipic acid

adipic acid

29

mfr. nylon

Aromatics

Benzene

5

solvent; general intermediate

Ethyl Benzene

8

mfr. styrene

Terephthalic acid

13

mfr. polyester

Styrene

9

mfr. polystyrene

Xylene

11*

solvent (*with individual isomers ranked 16, 39)

Toluene

15

solvent; mfr. TNT

Cumene

17

mfr. phenol, acetone

Phenol

20

antiseptic; mfr. bakelite, aspirin

Nitrobenzene

30

mfr. aniline

Bisphenol A

31

mfr. polycarbonate, polyurethane, epoxy resins

Aniline

35

intermediate; mfr. dyestuffs

caprolactam

32

mfr. nylon-6.

phthalic anhydride

40

intermediate

The Prehistory of Organic Chemistry.

A number of organic chemicals were isolated or synthesized prior to 1631, although of course there was no knowledge of their true chemical nature (Lemery in late-seventeenth century classified all chemicals as mineral, vegetable or animal), and their purity was doubtful.

Ethyl alcohol has been known since antiquity, and distillation (or freezing) made it possible to obtain it in concentrations that would kill the fermentation yeast. Acetic acid was first known in dilute form as vinegar, and supposedly it was concentrated by Geber in the eighth century. (Payen 961).

Tartrate salts were used as medicines in the sixteenth century. Valerius Cordus (1515-1544) made diethyl ether (“sweet oil of vitriol”) in 1540 by adding sulfuric acid to ethyl alcohol. The details were published in De Artificiosis Extractionibus (1561). (Sneader 79). Succinic acid was isolated by George Baeyer (Agricola) from Baltic amber in 1546. (Poinar 23) Benzoic acid was prepared by Blaise de Vigenere, by subliming gum benzoin, in the late-sixteenth century. (Von Meyer, 103ff). Lead acetate was dry-distilled by Jean Beguin in 1610, obtaining acetone, the “burning spirit of Saturn” (Bourzat).

Organic Chemicals in Canon

Ethanol (ethyl alcohol) and Methanol (methyl alcohol)

Of course, West Virginia has a long tradition of distilling moonshine. This tradition is referred to in Offord’s “Class of ’34” (Grantville Gazette 4). Homemade booze can contain both methanol and ethanol. Methanol fractions off at a lower temperature than ethanol, which is why “people who know what they are doing throw out the first couple of ounces of flow to get rid of the methanol.”

Ethanol is a fuel for machines, not just a pick-me-up (or knock-me-down) for people. The tractor in Lutz and Zeek, “Elizabeth” (Grantville Gazette 8) was converted to run on ethanol. In Mackey, “Ounces of Prevention” (Grantville Gazette 5), Nicki Jo Prickett tells Rubens and Scaglia that high-proof alcohol is a good antiseptic.

A “methanol plant” is in operation in Grantville by May, 1632. (Mackey, “The Prepared Mind.” Grantville Gazette 10), but the particulars of its operation aren’t disclosed. The logical way to make methanol is by destructive distillation of wood.

In 1633, the USE builds its first aircraft and fuels them with “M85,” meaning a mixture which is 85% methanol, 15% gasoline. (Flint, 1633, Chapter 27). The same concoction is used by the first civilian airliner. (Huff and Goodlett, “The Monster”, Grantville Gazette 12).

Ether

Diethyl ether, the anesthetic, is used by Sharon Nichols during the operation on Ruy Sanchez in April 1634. Flint and Dennis, 1634: The Galileo Affair (Chapter 39). It was clearly made by Stoner, not a leftover from year 2000. It couldn’t have been available until after December 1632 since Doctor Sims then was still pulling teeth without anesthetizing his patients. Wentworth, “Here Comes Santa Claus” (Ring of Fire).

Rochelle Salts (potassium sodium tartrate)

In July 1631, Dr. Phil was fascinated by Tasha Kubiak’s cigarette lighter. It used a piezoelectric crystal, and Dr. Phil obtained a cheat sheet for preparing Rochelle’s salt, which has piezoelectric properties. He succeeded. Because of their utility in radios, he calls them “Gribbleflotz Aeolian Crystals.” See Offord, “Dr. Phil’s Amazing Lightning Crystal” (Grantville Gazette 11)

We can guess what the cheat sheet said. “Tartrate” means a salt of tartaric acid, an organic acid. Cream of tartar (potassium bitartrate) is a crystalline deposit found in wine casks, and was known to the downtime alchemists. Dissolving cream of tartar in a hot solution of sodium carbonate forms Rochelle’s salt (EB11/Tartar). Rochelle’s salt was first prepared around 1675, so there wasn’t much doubt that it was within down-time capabilities.

Coal tar dyes

Stoner daydreams about “Victorian coal tar dyes . . . reds, purples, good God, mauve!” at the end of Lackey, “To Dye For” (Ring of Fire). There is reference to “Mr. Stoner’s dye shops” in Huff, “Other People’s Money,” Grantville Gazette 3. In March 1634, Rita, Melissa and Sharon are wearing makeup incorporating Stoner’s chemicals. (Flint and Dennis, 1635: The Cannon Law, Chapter 23). In winter 1633-34, Nicki Jo tells the Spanish that most of Essen Chemical’s benzene feedstock is “going to produce aniline dyes.” (Mackey, “Ounces of Prevention,” Grantville Gazette 5).

Penicillin

Bob Gottlieb has pointed out (“They’ve Got Bread Mold, So Why Can’t They Make Penicillin?” Grantville Gazette 1) the problems of isolating microorganisms which produce antibiotics in useful concentrations. Fortunately, in May 1632, Amy Kubiak and Lori Fleming discovered that Grantville’s high school science lab had a sample of “high yield” Penicillium notatum. (For justification of this find, see Mackey, “Crude Penicillin: Potential and Limitations,” Grantville Gazette 10.) Amy and Lori passed their find on to two visitors from Cologne. Who in turn set up a laboratory and worked on finding just the right culture medium.

By April 1634, the Antonite hospital in Cologne was ready, with some reluctance, to administer penicillin to people. At that point, they only had enough to treat one person for ten days, but by January 1635, they had stock enough to meet the needs of the entire city . . . some forty thousand people. See Mackey, “The Prepared Mind” (Grantville Gazette 10). Nonetheless, in June 1634, Bill Hudson complains that the up-timers in Amberg don’t have penicillin (or the macrolide antibiotic erythromycin). Flint and DeMarce, 1634: The Bavarian Crisis, Chapter 25.

Sulfanilamide

In May, 1632, Nicki Jo Prickett tells Franz Dubois that the synthesis for sulfanilamide is in one of her organic chem textbooks. (Mackey, “The Prepared Mind”, Grantville Gazette 10), but it’s clear that no one had made it yet. Grantville does have it by fall, 1633—the cabinet votes to “send our existing stock of chloramphenicol and most of our sulfa drugs to Luebeck and Amsterdam, along with as much DDT as we can manage . . . ” (1633, Chapter 35).

By the winter 1633-34, the Essen Chemical Company is producing small quantities of sulfanilamide (apparently in preference to Grantville’s premiere antibiotic, chloramphenicol).

See Mackey, “Ounces of Prevention” (Grantville Gazette 5).

Sharon uses “sulfa powder” on Ruy Sanchez in April, 1634 (Flint and Dennis, 1634: The Galileo Affair, Chapter 43). And when the Archduchess Maria Anna’s infected hands are treated in August 1634 (Flint and DeMarce, 1634: The Bavarian Crisis, Chapter 53), it’s with “sulfa.”

A fairly complete synthesis of sulfanilamide appears in M&B 757. The starting material is aniline (aminobenzene); the reagents are acetic anhydride, chlorosulfonic acid (nasty stuff!), ammonia, and acid.

It isn’t a difficult synthesis; it’s a common assignment in a sophomore organic chem lab (Lehman 389). Of course, the sophomores don’t have to make the chlorosulfonic acid themselves. That requires reacting chlorine gas with sulfuric acid under pressure.

The intermediate resulting from the acetylation of aniline is acetanilide, and it has some interesting uses. EA “Reaction, Chemical” says that it retards the decomposition of hydrogen peroxide. EB11 mentions (“Edgar Quinet” and “Pharmacology”) that acetanilide is an antipyretic (reduces fever), albeit not a very safe one. Acetanilide is structurally related to a modern antipyretic and analgesic, acetaminophen (Tylenol®). In fact, if you react the acetic anhydride with hydroxyaniline rather than with aniline, you get acetaminophen.

Hexachlorobenzene

By the winter 1633-34, the Essen Chemical Company is producing hexachlorobenzene, and marketing it as an insecticide (remember, fleas carry the plague). See Mackey, “Ounces of Prevention” (Grantville Gazette 5). This is most likely done in the obvious way; bubbling chlorine gas into benzene. Based on the discussion in EB11/Benzene, this reaction might be facilitated by ferric chloride. But there are other chlorinating agents, notably sulfuryl chloride and the chlorosulfonic acid. EB11/Chloroform mentions that when gaseous chloroform (trichlormethane) is passed through a red-hot tube, hexachlorobenzene is obtained, together with perchloroethane and perchlorethylene.

DDT

The USE delegation to England brought with it “several pounds of the DDT which the fledgling American chemical industry was starting to produce.” (Flint, 1633, Chap. 21). There aren’t a lot of date cues as to when the delegation left home (Eric’s motto is “vague is good”) John Bogan’s proposed timeline has the delegation departing in June, 1633.

In the standard synthesis of DDT, you react two equivalents of chlorobenzene with one of trichloroacetaldehyde, in the presence of sulfuric acid. (M&B650, problem 11; Bailey, 252; CCD; Solomons 1024).

In order to have DDT in June 1633, the reactants (chlorobenzene and trichloracetaldehyde) must have been synthesized earlier. But neither are natural products; both of them must be intermediates synthesized from other chemicals.

The chlorobenzene certainly would have been obtained by chlorinating benzene. The standard reagent for this purpose is chlorine gas in combination with a ferric chloride catalyst, and the reaction is one taught in introductory organic chemistry classes. (M&B 351-2). Benzene, in turn, can be obtained from oil or coal.

Chlorine reacts with acetaldehyde at room temperature to yield monochloroacetaldehyde. To get the trichlorinated analogue, you need to increase the temperature to 80-90 deg. C. (McKetta, 121). I imagine this was discovered by a moderate amount of trial and error. The acetaldehyde might be isolated from plants, but an alternative is to oxidize ethyl alcohol with a strong oxidizing agent, and remove the acetaldehyde before it is oxidized any further. (M&B 621, 625).

So this all implies the availability, by June 1633, of the following organic chemicals in respectable purity: DDT, chlorobenzene, benzene, mono- di- and trichloroacetaldehydes, acetaldehyde, and ethyl alcohol.

Trichloroacetaldehyde is interesting in its own right. It reacts with water to form chloral hydrate—the solution of chloral hydrate in alcohol is known as “knockout drops” or a “Mickey Finn.”

Chloramphenicol (Chloromycetin)

Gottlieb, “They’ve Got Bread Mold, So Why Can’t They Make Penicillin? ” (Grantville Gazette 1) opined that “While it will not be easy to produce chloramphenicol with the resources at hand, it can be done—with a lot of Grantville’s money and skilled people. Early production would probably be limited to bucket quantities, however, enough to treat perhaps a hundred people per month. Only with the advent of stainless steel and chemical plants will production on a larger scale become likely.”

It appears that the chloramphenicol project was originally assigned to Stoner. By sometime before September 1633 (the date cue is in 1633, Chap. 18), he is already at the “yield improvement” stage. (Flint, 1633, Chapter 15).

In the course of the siege of Amsterdam, Anne Jefferson, on Stearns’ orders, contrives to pass a monograph entitled, “How to Make Chloramphenicol” to Rubens, and thus to Don Fernando. Flint, “Portraits” (Grantville Gazette 1, paper only). This identifies the ingredients needed to make chloramphenicol, recites the steps by which they are reacted, and diagrams the apparatus required.

After Gustavus Adolphus learns of this surreptitious tech transfer, Mike Stearns attempts to calm down the angry emperor by pointing out that chloramphenicol “is so hard to make in any quantities—even for us, much less the Spaniards—that providing them with the formula was almost entirely a symbolic gesture. I doubt if more than a dozen Spanish soldiers will benefit from it, over the next year—and they will be entirely top officers, not the men who would be storming the ramparts.” (TBW Chapter 25).

That’s different from what Rubens tells Don Fernando, but Rubens is hardly an expert on alchemical matters. Rubens is correct that the Low Countries are well supplied with artisans and workshops, but being able to make the apparatus isn’t the same as being able to figure out the formulae and make the chemicals in pure form.

Chloramphenicol is actually more complex than DDT, even though it has only one phenyl ring. To complicate matters further, this structure has two “optical centers,” which means that it has four optical isomers . . . and only one of them is antibacterially active.

There are several possible synthetic strategies, and it is not clear which one was used by the Grantvillers. I think the most likely documentary source of the synthesis is a problem set forth in Solomons, Organic Chemistry (page 967, 1992 edition; page 996, 1995 and 1996 editions). Intermediates A-E are given only as molecular formulae so the reader has to deduce them. The steps are

(1) condensation of benzaldehyde with 2-nitroethanol

(2) reduction of nitro group to an amino group

(3) chlorination with dichloroacetyl chloride

(4) acetylation of hydroxyls with acetic anhydride (this is a protective step)

(5) ring nitration with nitric acid in presence of sulfuric acid (mentioned by Mackey, “Ounces of Prevention” (Grantville Gazette 5))

(6) hydrolysis to remove the acetyl groups

I have a few comments. In step (1), nitroethanol is explosive; alternative syntheses exist (Ishar 232). In step (2), the reduction as taught by Solomons is with hydrogen and an unidentified catalyst. The catalyst of choice is palladium but that isn’t available in the 1630s. So Stoner probably experimented with other reducing agents. The basic chloramphenicol patent (2483884) suggests possible use of stannous chloride, sodium hydrosulfite, ferrous sulfate, iron-acetic acid or zinc-sulfuric acid. Solomons’ synthesis yields a mixture of four isomers, but Solomons doesn’t explain how to resolve them. Finally, the chlorination step can be deferred until after hydrolysis and isomer resolution (Bhat 731); this might reduce costs.

Aspirin.

With up-time aspirin selling for $20 a tablet on the “black market,” Katie Jackson asked her boss, the Nobili of Nobili’s Pharmacy, for a cheat sheet for aspirin. Ted and Tracy passed it on to Dr. Phillip Gribbleflotz, who reluctantly became the “Aspirin King” in July or August 1631. See Offord, “Dr. Phil’s Amazing Lightning Crystal” (Grantville Gazette 11). He preferred to call it Sal Vin Betula, however. Offord, “Feng Shui for the Soul” (Grantville Gazette 17)

We don’t know how Dr. Phil made aspirin, but we can guess. Aspirin is acetylsalicylic acid (or its salt), which is itself a derivative of salicylic acid (ortho-hydroxybenzoic acid). Salicylic acid can be isolated from the bark of the willow tree (Salyx), hence its name, and then acetylated, making aspirin an example of a semisynthetic biochemical. Back in 1859, acetyl chloride was the reagent. Later, Hoffman (1893) exploited salicylic acid’s reaction with acetic anhydride, catalyzed by phosphoric acid.

In “Sal vin betula,” “sal” means “salt” and “betula” is the birch tree. The word “vin” is not Latin, but perhaps Phil was thinking of vinum, wine. Salicylic acid is also found in the volatile oil distilled from the bark of the sweet birch (Betula lenta). My guess is that Phil used acetyl chloride, itself made by reacting acetic acid (distilled from vinegar) with thionyl dichloride. (If so, then thionyl chloride was available at a much earlier date than that predicted in part 2 of this series.)

The salicylic acid can itself be synthesized by one of the methods set forth in EB11/”Salicylic Acid.” One example is to take sodium phenolate (a salt of phenol, which is found in coal tar), react it with carbon dioxide, and then acidify. This is a high pressure reaction and is therefore not so likely to have been practiced in the early post-Ring of Fire period.

Sildenafil (Viagra®)

No, no one has actually made Sildenafil. Rather, in September, 1635, Dr. Phil was asked to make it. Offord, “The Creamed Madonna” (Grantville Gazette 19). It has several heterocycles, and I think it beyond 1630s capabilities (see Appendix).

Natural Gas

In June 1631, Chad Jenkins recognized that he could sell cars if he could convert them to run on natural gas. He urged his employees to “buy lots of pressure tanks and their connections first,” because “cars are everywhere but not pressure tanks.” Rittgers, “Von Grantville” (Grantville Gazette 7).

In mid-1633, LeeAnn thought, “Thank God natural gas supply wasn’t a problem in Grantville.” (Schillawski and Rigby, “Recycling,” Grantville Gazette 6). In 1634, Frau Hollister’s house is still heated with natural gas. (DeMarce, “Not At All the Type,” Grantville Gazette 7).

Propane

In Offord and Boatright, “Dr. Phil’s Amazing Essence of Fire Tablets,” Dr. Phil complains that as of 1633, “there had been talk of producing ‘propane,’ but for now that was as far off as his much-needed aluminum.” This suggests that Grantville’s natural gas was mostly methane (see part 4).

Formaldehyde

This simple organic chemical has clearly been made by 1633, when Dr. Phil experiments with formalin. He uses it first to make hexamine, and later, bakelite (see below).

Hexamine (hexamethylenetetramine) and RDX (cyclotrimethylenetrinitramine)

In 1633, Dr. Phil reacts spirits of hartshorn (ammonia) with formalin (formaldehyde). Offord and Boatright, “Dr. Phil’s Amazing Essence of Fire Tablets,” Grantville Gazette 7. It turns out that’s exactly what you need to make hexamine, the key ingredient of fuel tablets. (MI/Methenamine).

It’s also clear that this is dumb luck. Dr. Phil got a new chemical and was mixing it with a chemical he already had to see what happened. He didn’t know whether the reaction product would be poisonous or not, and when his laborant told him it tasted “sweet,” Phil hoped that he had succeeded in synthesizing sugar! (The synthesis of sucrose, by the way, has been called the “Mount Everest of Chemistry” and it was accomplished by Raymond Lemieux in 1953. Who, in the Eighties, was one of my patent clients.)

But the hexamine wasn’t sweet enough. Fiddling around, they discovered that when ignited, it produced a strong heat with little soot.

The hexamine, in turn, was subsequently used by Brennerei und Chemiefabrik Schwarza, as early as winter 1633, to make the explosive RDX, albeit at pounds per week levels.

Bakelite

This is one of the early plastics, and Georg Heinz made bakelite insulators in 1634. EA/”Bakelite” would have told him that it is a copolymer of phenol and formaldehyde. Offord, “Feng Shui for the Soul,” Grantville Gazette 17. According to his colleague, Michael Siebenhorn, the bakelite was derived, ultimately, from “chemicals from the gas works.” This is probably a reference to coal gas.

Casein

In winter 1631-32, casein plastic is made by heating a mixture of milk and vinegar. (Offord, “Bootstrapping,” Grantville Gazette 11). Casein is also referred to in DeMarce, “Songs and Ballads” (Grantville Gazette 14).

Medicinal Herbs

Stoner is growing both marijuana and poppies, for analgesic use. Flint 1633; Ewing, “An Invisible War,” (Grantville Gazette 3); Huff and Goodlett, “Birdie’s Village” (1634: The Ram Rebellion).

The healer Tibelda has yarrow, tincture of meadwort (contains salicylic acid), a tonic comprising lily of the valley (various poisonous cardiac glycosides), and foxglove (digoxin). Viehl, “A Matter of Consultation” (Ring of Fire).

Natural Rubber

Natural rubber is a polymer of isoprene. It is a 1, 3-diene, meaning that it has two C=C bonds separated by a single bond. There are two possible configurations for hooking up the isoprene units. Natural rubber features the cis configuration (rendering it elastic) and gutta percha, another isoprene polymer, the trans configuration (making it more crystalline).

Natural rubber has been trickling into post-Ring of Fire Europe. This was initially thanks to Hevea brasiliensis tapping by Amazonian Indians under the direction of Henrique Pereira da Costa. (Cooper, “Stretching Out, Part Two: Amazon Adventure”, Grantville Gazette 12). Tapping began sometime in 1633, but ceased abruptly in early 1634 when Henrique was forced to flee into the rain forest to avoid arrest by the Inquisition.

In 1634, rubber from Hevea guianiensis of Suriname, and Castilla elastica from Nicaragua, was collected under the direction of Maria Vorst, Philip Jenkins and David Pieterszoon de Vries. Cooper, “Stretching Out, Part One: Second Starts” (Grantville Gazette 11), Part Three: Maria’s Mission” (Grantville Gazette 14); “Part Four: Beyond the Line” (Grantville Gazette 16). Their first shipment arrived in Hamburg in late 1634. There should be additional shipments every six months or so, at least as long as the colony of Gustavus by the mouth of the Suriname River survives.

And then there’s milkweed rubber. In 1634, Dr. Phil gets milkweed latex from Celeste’s daughter and her friends. (Offord, “Feng Shui for the Soul,” Grantville Gazette 17).

In winter 1633-34, captured Brazilian rubber (Henrique’s first shipment?) was vulcanized by Henri Beaubriand-Lévesque, Henri figured out the methodology from his set of the fifteenth edition of Encyclopedia Britannica. Perhaps with a little help from Doctor Gribbleflotz. Offord, “Letters from France” (Grantville Gazette 12).

A rather weird method of synthesizing isoprene is given in EB11/terpenes. Isoprene can also be made by decomposing turpentine (1882), or by chlorinating isopentane (found in petroleum) and then removing units of HCl to create the necessary double bonds (Molinari, 109). These alternative methods would need to be reinvented.

Quinine

Quinine, an antimalarial agent made from the South American cinchona bark, was the Holy Grail of the nineteenth century chemical industry. (It wasn’t actually synthesized until 1944 or 2001, depending on who you ask, and synthetic quinine is not commercially significant.) Mbandi delivers 50,000 seeds of the cinchona roja to Dr. Nichols in winter 1634-35. (Cresswell-Jones, “Mulungu Seed,” Ring of Fire II).

Artemisia

Artemisia is another antimalarial drug, but it is an herb derived from the leaves of the shrub Artemisia annua, and used in Chinese medicine since the fourth century AD. Nichols, talking to Piazza, says that a “private expedition” to “another continent,” apparently led by “Dieter,” was carrying Artemisia “last year.” (Cresswell-Jones, “Mulungu Seed,” Ring of Fire II). By “Artemisia,” I assume that he means the drug in herbal form, which the Chinese call Qinghao.

The active ingredient, artemisinin (Chinese Qinghaosu), was purified by the Chinese in 1972. The purification was tricky; extracts of Artemisia had been screened several years earlier but found inactive (artemisinin wasn’t soluble in the initially tried solvents, water and ether).The first English academic publication regarding artemisinin appeared in 1979. (Hsu; Arnold).

While it is possible that Nichols came across a medical journal article about it, it’s more likely Diane Jackson knew of Qinghao’s use in Vietnam (either as a traditional remedy, or information passed on by the Chinese government to the Viet Cong, which eventually became known to a larger circle of Vietnamese).

Artemisia annua is hardy to zone 7. While not found in the wild in Marion County WV (USDA), it has been spotted in Mannington gardens (Runkle, private communication). It produces 0.01-1% artemisinin, and greater quantities of convertible artemisinic acid (ienica.net).

Insulin

In OTL, the first successful medicinal use of insulin was in 1922. The insulin in question was an ox-extract.

In Spring, 1632, the diabetic “Slam Dunk” Cunningham supports research on purifying animal insulin. Small quantities are purified by an alchemist-hireling in summer 1632. Evans, “Dog Days” (Grantville Gazette 15).

****

Continued, part 4.

Author’s note: Bibliography will be in Appendix published in “Gazette Extras” on www.1632.org after Part 5 is published.

****

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About Iver P. Cooper

Iver P. Cooper, an intellectual property law attorney, lives in Arlington, Virginia with his wife and two children. Two cats and a chinchilla rule the household with iron paws. Iver has received legal writing awards from the American Patent Law Association, the U.S. Trademark Association, and the American Society of Composers, Authors and Publishers, and is the sole author of Biotechnology and the Law, now in its twenty-something edition. He has frequently contributed both fiction and nonfiction to The Grantville Gazette.

 

When not writing (or trying to get an “orange blob” off his chair so he can start writing), he has been known to teach swing dancing and folk dancing, or to compete in local photo club competitions. Iver adds, “I can’t get my wife to read my fiction, but she has no trouble cashing the checks.”

Iver’s story “The Chase” is in Ring of Fire II