A suitable historical answer gives both the chemical transformation and the means of isolating a reasonably pure product. The following are preparative principles, with modern chemical formulas; they are not instructions for self-preparation of medicines. In particular, hydrogen cyanide, mercury compounds and arsenic compounds present serious toxicity hazards. Hydrogen cyanide is extremely volatile, can be absorbed by several routes, and its odour is an unreliable warning.[ref]
Hydrogen cyanide emergency response information by NIOSH. Agent Characteristics; Routes of Exposure; warning that smell does not provide adequate protection
For hydrocyanic acid, a customary early nineteenth-century route is the controlled distillation of potassium ferrocyanide with dilute sulfuric acid and water. Hydrogen cyanide passes into the distillate; nonvolatile salts remain behind. A generating flask, efficient laboratory condenser and chilled receiver are needed because hydrogen cyanide is readily lost. The contemporary account of hydrocyanic acid preparation in Pharmacopoeia Castrensis Ruthenica in The British and Foreign Medical Review (1842) specifically describes the ferrocyanide–sulfuric acid method and its losses on imperfect condensation. The concentration must be determined analytically before any defined dilution: a nominal starting mixture does not establish the final strength.[ref]
Pharmacopoeia Castrensis Ruthenica in The British and Foreign Medical Review (1842). Processes for obtaining Hydrocyanic Acid
At the level of the released cyanide, the essential acid-base reaction is . This equation alone is not a complete equation for decomposing the stable ferrocyanide coordination complex. Concentrated sulfuric acid can lead to different decomposition chemistry, so the specified dilution is meaningful.For formic acid, gently heat oxalic acid with glycerol and some water, then separate the aqueous formic acid by distillation. The useful net transformation isThe glycerol participates through intermediate esters and is regenerated rather than consumed in this net equation. Marcellin Berthelot's 1856 account describes the carbon dioxide evolution, subsequent water addition and distillation, and reuse of the residual glycerol. Overheating is disadvantageous because the formic acid can decompose further to carbon monoxide and water. The method therefore separates a volatile acid from a much less volatile carrier; it is not merely the dry destructive heating of oxalic acid.[ref]
Verfahren zur Darstellung der Ameisensäure by Marcellin Berthelot. Polytechnisches Journal 140 (1856), p.78, report of the March 1856 communication
For oxalic acid, oxidize a carbohydrate, such as sucrose or starch, with nitric acid; concentrate the resulting chemical solution appropriately and cool it to obtain crystals, followed by recrystallization. Nitrogen oxides evolve, and excessive oxidation can carry carbon onward to carbon dioxide, so an idealized single-product equation would conceal losses. The use of starch and nitric acid for oxalic acid production is explicitly documented in an 1850 account of nitric oxide recovery.[ref]
Polytechnisches Journal volume 117 (1850). p.466, “Verfahren das Salpetergas in Salpetersäure zu verwandeln”, opening example
An alternative already established before 1864 is alkaline treatment of sawdust, producing an oxalate which can be purified through sparingly soluble calcium oxalate.[ref]Polytechnisches Journal volume 162 (1861). report on chemical manufacture in South Lancashire, Oxalsäure section: alkaline sawdust route
Decomposing the isolated calcium oxalate with sulfuric acid separates much of the calcium as calcium sulfate:Filter off the calcium sulfate and crystallize the oxalic acid from the filtrate. The usual crystals contain two water of crystallization; a calculation for the anhydrous acid must not treat their entire mass as .For calomel, intimately combine mercury(II) sulfate, metallic Mercury and dry sodium chloride, then collect the volatile mercury(I) chloride in a cooler receiving chamber. The net change isThe extra metallic Mercury lowers the average oxidation state from +2 to +1. The product is purified by appropriate sublimation and washing to remove soluble contamination, particularly mercury(II) chloride. Both the chemical composition and the fine subdivision of the product matter: condensation through a chamber can give a powder rather than an adherent crystalline crust. This physical part of calomel preparation is described in the 1843 primary account in Polytechnisches Journal volume 87 (1843); the account's historical therapeutic claims are not adopted here.[ref]
Polytechnisches Journal volume 87 (1843). pp.209 onward, “Ueber Darstellung des Calomels als höchst zartes Pulver”, condensation and collecting chamber
For corrosive sublimate, heat dry mercury(II) sulfate with sodium chloride and collect the mercury(II) chloride in the cooler part of a suitable sublimation apparatus:Here no metallic Mercury is added. Nonvolatile sodium sulfate stays behind, while mercury(II) chloride is transferred and condensed. Further sublimation or recrystallization separates impurities. [ref]
Dictionary of Arts, Manufactures and Mines by Andrew Ure. Mercury, p.141, bichloride preparation and the following calomel account
The crucial distinction from calomel preparation is whether Mercury remains in the +2 oxidation state or is converted to +1.For the solid called arsenious acid, roast an arsenic-bearing ore in air and collect the volatile arsenic trioxide in cooler chambers; purify by resublimation. The essential oxidation is represented byActual ores also contain other chemical elements, so their roasting equations and gaseous by-products depend on composition. A contemporary 1860 report describes roasting arseniferous ores, collecting the volatile arsenic trioxide in chambers and refining it by another sublimation. It also demonstrates that apparently good material could contain antimony(III) oxide: physical appearance alone does not establish purity.[ref]
Polytechnisches Journal volume 156 (1860). p.77, report on the antimony content of glassy arsenious acid from Andreasberg
The product intended here is dry ; dissolving it does not make the bottled solid a pure crystalline hydrate .For tartar emetic, react antimony(III) oxide with potassium hydrogen tartrate in water. A small amount of water first gives intimate contact in a paste; subsequent heating with more water completes formation of the soluble potassium antimony tartrate. Filter away unreacted insoluble matter and cool the clear filtrate to crystallize the product. This sequence is directly described in a January 1864 discussion of the newly issued British Pharmacopoeia, rather than inferred from its later editions.[ref]
Chemical News volume 9 (1864). 30 January 1864, p.53, Antimonium Tartaratum: paste, standing, boiling and the oxide–bitartrate route
In the traditional antimonyl notation the underlying reaction, before assigning crystal water of crystallization, isThis notation expresses the overall composition; tartrate coordination complexes and water of crystallization need the qualification given in 4. The historical pharmaceutical use of tartar emetic does not make it a safe contemporary emetic.[ref]Antimony potassium tartrate by the National Poisons Information Service. Toxicity; gastrointestinal effects and systemic poisoning
For potassium chlorate, pass chlorine into hot concentrated potassium hydroxide. The disproportionation gives potassium chloride together with potassium chlorate:Concentration and cooling permit fractional crystallization of the much less soluble cold-water potassium chlorate, leaving much of the potassium chloride in the mother liquor; recrystallization improves purity. Cold dilute alkali instead favours hypochlorite, so the heating condition is essential. An economical contemporary manufacturing alternative uses hot calcium hydroxide and potassium chloride; the overall accounting isThe 1850 account in Polytechnisches Journal volume 118 (1850) describes a steam-heated stirred vessel and recovery by cooling, rather than an electrical manufacturing process introduced retrospectively.[ref]
Polytechnisches Journal volume 118 (1850). pp.424 onward, “Die neue Bereitungsart des chlorsauren Kalis”
The principal period groups were digitalis preparations, squill, broom, juniper oil, buchu, nitrous ether spirit, and several soluble potassium salts. They were grouped by observed promotion of urine flow, rather than by one common mechanism. The following are historical adult quantities per administration, expressed in the contemporary units; they are not present-day prescriptions.
- Digitalis preparations: powdered leaves, ½–2 grains; Infusum Digitalis, 2–4 fluid drachms; Tinctura Digitalis, 5–40 minims; digitalin, 1/40–1/10 grain in the period table. Historical digitalin was not simply a modern pure digoxin product.
- Squill: powder, 1–2 grains; Pilula Scillae Composita, 5–10 grains; Tinctura Scillae, 10–20 minims; Syrupus Scillae, ½–1½ fluid drachms.
- Broom: Decoctum Scoparii, 1–3 fluid ounces; Succus Scoparii, 1–4 fluid drachms.
- Buchu: powdered leaves, 20–40 grains; Infusum Bucco, 1–2 fluid ounces; Tinctura Bucco, 1–2 fluid drachms.
- Juniper oil: Spiritus Juniperi, 10–30 minims in the 1864 commentary. This unusually concentrated spirit contains one volume of juniper oil in ten; its dose must not be borrowed from a later, weaker formula.
- Nitrous ether spirit, Spiritus Aetheris Nitrosi: 30 minims to 2 fluid drachms.
- Potassium acetate: 10–20 grains; potassium citrate: 20–60 grains; potassium nitrate: 5–20 grains; potassium tartrate: 10–60 grains; potassium hydrogen tartrate: 20–60 grains.
- Ammonium acetate solution, Liquor Ammoniae Acetatis: 10–40 minims of the concentrated British preparation, diluted for administration.
[ref]
The Essentials of Materia Medica and Therapeutics by Alfred Baring Garrod (1865). Posological table: Digitalis, Infusum Digitalis, Scoparius preparations, Bucco preparations, Spiritus Aetheris Nitrosi, potassium salts and Liquor Ammoniae Acetatis; Liliaceae: squill preparations
[ref]The Prescriber's Analysis of the British Pharmacopoeia by John Birkbeck Nevins (1864). p. 61, Spiritus Juniperi, 1 in 10 and 10–30 minims
Other recognised period agents included dandelion and copaiba. The dandelion decoction was given in quantities of 1–2 fluid ounces, its soft extract in quantities of 10–30 grains, and its preserved juice in quantities of ½–2 fluid drachms. Copaiba was given in quantities of 15–30 minims, and copaiba oil in quantities of 5–20 minims. Their historical inclusion does not establish that they are suitable substitutes for current diuretic therapy. [ref]
The Essentials of Materia Medica and Therapeutics by Alfred Baring Garrod (1865). Posological table, Taraxacum preparations, Copaiba and Copaibae Oleum
The distinction between preparations matters more than a single “dose of the plant”: an infusion, tincture, juice and powder have different concentrations. Likewise, a salt's small historical diuretic dose is not its larger purgative dose. A modern explanation also separates a direct effect on renal tubules from improved cardiac output in appropriate heart failure: digitalis preparations cannot be understood simply as agents that make every kidney excrete more water. Modern digoxin is used for selected cardiac indications, rather than as a general treatment for low urine output. [ref]
Digoxin by MedlinePlus. Why is this medication prescribed?
The compositions must be specified ingredient by ingredient; the two alkaloidal solutions contain 4 grains per nominal fluid ounce, but one contains a morphine salt and the other strychnine.
Pulvis Jalapae Compositus contains powdered jalap 5 avoirdupois ounces, potassium hydrogen tartrate 9 avoirdupois ounces, and powdered ginger 1 avoirdupois ounce. Thus the mass proportions are 5:9:1, and jalap supplies one third of the powder's mass. This is a compound purgative, not pure jalap resin. [ref]
The Essentials of Materia Medica and Therapeutics by Alfred Baring Garrod (1865). Convolvulaceae, Jalapa, compound powder
Pilula Scillae Composita contains powdered squill 1¼ avoirdupois ounces, powdered ginger, ammoniacum and hard soap 1 avoirdupois ounce each, with treacle 2 avoirdupois ounces, or sufficient to make a pill mass. Using the specified 2 avoirdupois ounces of treacle, the whole is 6¼ avoirdupois ounces and contains one fifth squill by mass. The allowance of sufficient treacle makes consistency a compounding requirement, not a claim that every moist pill batch has an analytically exact 20% squill content. [ref]
The Essentials of Materia Medica and Therapeutics by Alfred Baring Garrod (1865). Liliaceae, British compound squill pill, distinguished from bracketed American formula
Liquor Morphiae Hydrochloratis contains morphine hydrochloride 4 grains, dilute hydrochloric acid 8 minims, rectified spirit 2 fluid drachms and distilled water 6 fluid drachms. Its conventional strength is ½ grain of morphine hydrochloride per fluid drachm, not ½ grain of free morphine. The small quantity of hydrochloric acid maintains an acid solution. [ref]
Liquor Strychniae contains strychnine 4 grains, dilute hydrochloric acid 6 minims, rectified spirit 2 fluid drachms and distilled water 6 fluid drachms. Dissolve the strychnine in the acid mixed with part of the water, using the prescribed assistance of heat, then add the spirit and remaining water. Its conventional strength is ½ grain of strychnine per fluid drachm. Acid promotes solubility by forming a soluble salt of the alkaloid. [ref]
For the last two solutions, the stated historical strengths use the nominal 8 fluid drachms of spirit and water. The extra few minims of dilute acid must still appear in the actual recipe; treating all ingredient volumes as perfectly additive would not give an exact modern analytical concentration.