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Plan B. First, we make acetanilide (phenylacetamide). This was once used as an analgesic; the body metabolizes it into acetaminophen (TylenolR). It's derivable as follows: (coal tar -› nitrobenzene -› aminobenzene (aniline) -› acetanilide, the last step requiring acetyl chloride (*MI 5) or acetic anhydride (*M amp;B 742). Acetanilide is already, implictly, in canon, because it's an intermediate in the standard (undergraduate lab) synthesis of the antibiotic sulfanilamide.

Now, here's the trick. We use the "Duff Reaction" (*MI 1160), in which an aromatic amine is formylated at the para position by hexamethylenetetramine (hexamine, an oligomer of formaldehyde and ammonia) in the presence of an acidic catalyst. While MI assumes that the aromatic amine is a dialkylamine, I am guardedly hopeful that acetanilide (a monoacylamine) will react properly.

Does hexamine sound familiar? Dr. Phil made it back in 1633. (Offord and Boatright, "Dr. Phil's Amazing Essence of Fire Tablets," Grantville Gazette 7.) The preferred acid used to be boric or acetic acid (Ahluwalia 315); it's now trifluoracetic acid if yields of the para product are low. (**March 490).

II) Thiosemicarbazide. Made from potassium thiocyanate and hydrazine (*CCD 868). The "thiocyanate" is made by reacting sulfur with alkali cyanide (*C amp;W 301).

I think that we are looking at first availability in 1634-5.

Para-aminosalicylic acid. Heat meta-aminophenol with ammonium carbonate or potassium bicarbonate under pressure (*MI 62, *CCD 48).

The former may be obtained by reduction of meta-nitrophenol (*MI 89); I would reduce with iron and dilute hydrochloric acid (*M amp;B 725). To make m-nitrophenol, it's standard to boil diazotized meta-nitroaniline with sulfuric acid and water (*CCD 624; *MI 741, **Eagleson 700); treating phenol with nitric acid won't work as you get the para- and ortho isomers. Derivatizing nitrobenzene at the meta position is difficult because nitrobenzene is about 100,000 times less reactive than benzene.

You can make meta-nitroaniline from meta-nitrobenzoic acid (*MI 736). Or from aniline, by acetylation, nitration, and then removal of the acetyl group by hydrolysis. (*CCD 619). Note that the reagents aren't spelled out. Diazotization (*M amp;B 773) is standard in dyemaking and Stoner has certainly introduced it by 1634.

An alternative route to meta-aminophenol is "by reaction of alkali hydroxides with 3-aminobenzene sulfonic acid or from resorcinol and ammonia in the presence of catalysts". (**Eagelson 62). If we have Eagleson to consult, then we might have PASA by 1635.

Streptomycin. This was isolated in 1943 from a strain of Streptomyces griseus, a microbial fungus found is soil. Re-isolating it in the new universe is essentially a matter of chance; and the more samples, from diverse sources, are screened for the presence of antibiotic-producing fungi, the more likely it is that we will find one that produces streptomycin.

To give you an idea of what the odds are like, in 1946 Waksman noted that "the production of streptomycin . . . is characteristic of only a few strains of S. griseus," and that in a recent screen of 40 griseus cultures, none produced streptomycin and only one produced an interesting antibiotic.

While the chemical structure is known (Merck Index), devising a synthesis will likely be extremely difficult. It's an aminoglycoside, which is a chemical class several orders of magnitude more complex than anything reported to have been synthesized in canon. It has three rings, each heavily substituted. The first total synthesis of streptomycin was achieved in 1974 by Umezawa. It is unlikely that the chemical synthesis is described in Grantville Literature.

Conclusion

In medieval and even premodern times, it was believed that the "royal touch" could cure the skin disease scrofula, a swelling of the lymph nodes caused by tuberculosis. On one Easter Sunday, Louis XIV touched 1600 sufferers (White). But the chemistry of Grantville offers a surer solution to the "white plague."

Bibliography:

Grantville Literature:

(The specified edition is merely the one I consulted.)

[MI] Merck Index (8th ed. 1968).

[M amp;B] Morrison amp; Boyd, Organic Chemistry (2d ed. 1966).

[CCD] Hawley, Condensed Chemical Dictionary (8th ed. 1971).

[G amp;G] Goodman amp; Gilman, The Pharmacological Basis of Therapeutics (8th ed. 1993).

Solomons, Organic Chemistry (6th ed. 1996).

[C amp;W] Cotton amp; Wilkinson, Advanced Inorganic Chemistry (1972).

Maybe:

Eagleson, Concise Encyclopedia of Chemistry (1994).

Remington, The Science and Practice of Pharmacy (21st ed., 2005)(need to check pre-RoF edition!)

Johnson, Invitation to Organic Chemistry (1999)

March, Advanced Organic Chemistry (3d. ed. 1985).

Other:

Waksman, Isolation of streptomycin-producing strains of Streptomyces griseus", J. bacteriol., 52:393-7 (1946)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC518198/pdf/jbacter00673-0139.pdf

Umezawa, Total Synthesis of Streptomycin, J. Antibiotics, 27: 997-9 (1974)

http://www.journalarchive.jst.go.jp/jnlpdf.php?cdjournal=antibiotics1968 amp;cdvol=27 amp;noissue=12 amp;startpage=997 amp;lang=en amp;from=jnlabstract

Ryan, Tuberculosis: the greatest story never told (1992)

Vardanyan, Synthesis of Essential Drugs (2006).

Sriram, Medicinal Chemistry (2010).

Ahluwalia, Organic Reaction Mechanisms (2005).

Watt's Dictionary of Chemistry, Vol. 1 (1888).

White, A History of the Warfare of Science with Theology in Christendom (1896), chapter XIII

http://cscs.umich.edu/~crshalizi/White/medicine/fetich.html

[KO] Kirk-Othmer Encyclopedia of Chemical Technology, 4th ed., Vol. 13 (1995) and 20 (1996).

****

Hydrogen: The Gas of Levity

Iver P. Cooper

Hydrogen was probably made by Paracelsus in the sixteenth century, and was described by Johann Baptista van Helmont in 1625. It's not only the gas with the greatest intrinsic lifting power (once called "levity"), hence very important for airship development, it's also an extremely important industrial chemical.

Before the twentieth century, the principal uses of hydrogen were in ballooning and in the oxyhydrogen torch. Later, it was used to hydrogenate and reduce other chemicals. Hydrogenation of oils was introduced in 1897-1913, and the Haber-Bosch process for manufacture of ammonia from nitrogen and hydrogen in 1913. Water gas (a hydrogen-carbon monoxide mixture) was used to make methanol in 1922 and hydrocarbons (Fischer-Tropsch process) in 1935.

Hence, there will be many parties interested in finding ways to produce it cheaply, in acceptable purity, on a large scale.

The impurities will vary depending on the nature of the production process, but they typically include carbon monoxide and dioxide, nitrogen, oxygen, water vapor, hydrogen sulfide, carbon disulfide, arsine, phosphine, silane and methane. (Ellis 598). These impurities reduce lift (1% air reduces lift by 1%) and some of them attack the gas cell envelope (Greenwood 234).

Under a pressure of one atmosphere, at a temperature of 20oC (68oF), one pound of hydrogen gas will occupy 191.26 cubic feet (so 1000 cubic feet is 5.23 pounds), and one kilogram will occupy 11.94 cubic meters (one cubic meter is 35.2 cubic feet). A 10oC increase in temperature will cause it to expand by 3.4%, and the corresponding temperature drop will contract it by the same percentage.