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

Written by Iver P. Cooper

 

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 (64.5^oC), which is less than the boiling point of water or of ethanol (78.3^oC). 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. ...