Part 19

This coniine triumph of synthetic chemistry has been followed by many others of a similar character, and now all the alkaloids mentioned above in connection with pyridine have been produced artificially. Piperine was synthesised by Ladenburg and Scholtz in 1894; atropine together with other solanaceous alkaloids, and cocaine[4] by Willstätter in 1901–2; and nicotine by Pictet in 1903. The structure of these alkaloids is considerably more complicated than that of coniine; atropine, for example, is represented by the formula

H H_{2} H_{2}C----C----C CH_{2}OH | / \ | | N--CH_{3} CH--O--CO--CH | \ / | H_{2}C----C----C C_{6}H_{5} H H_{2}

The molecule of quinoline contains a benzene and a pyridine nucleus condensed thus:--

HC CH \ C / // \ / \\ HC || CH HC || CH \\ / \ // \\/ C \// HC N

Among the alkaloids of the quinoline group may be mentioned those of cinchona bark and nux vomica. The constitution of these alkaloids is very complex, and in most cases but little understood. As an example of the cinchona group quinine may be taken. Its structure is probably

CH / | \ / | \ H_{2}C CH_{2} CH--CH==CH_{2} | | | H_{2}C HO·C CH_{2} \ / | / \/ | / /\ | / / \ | / CH_{2} N / HC C // \ C / \\ CH_{3}OC| \ / |CH HC| | | |CH \\ C \ // HC N

the formula being C_{20}H_{24}N_{2}O_{2}. Quinine has not been completely synthesised, but it has been prepared from cupreine, another cinchona alkaloid. The strychnos alkaloids likewise have not yet been artificially prepared, and their structure still requires elucidation.

The derivatives of isoquinoline, which was discovered by Hoogewerff and van Dorp in 1885, include some of the opium alkaloids, papaverine and narcotine, for example. Morphine and codeine do not, strictly speaking, fall into either of the three groups mentioned; our knowledge of the chemical nature of these substances has been much advanced recently, and it is probable that their synthesis will be effected before long.

HC CH // \ C / \\ HC| \ / |CH HC| | | |N \\/ C \ // HC CH

Isoquinoline.

One of the most beautiful pieces of work on the synthesis of vital products during recent years was the artificial preparation by Fischer (1895–98) of the bases caffeine and theobromine. The processes employed are too long and complicated to be described here, but the formulas may be given, since they demonstrate the close relationship which exists between the two substances.

(CH{3})N-----CO HN-----CO | | | | | | | | CO C-N(CH{3}) CO C-N(CH{3}) | || \ | || \ | || /CH | || /CH (CH{3})N-----C-N (CH{3})N-----C-N

Caffeine. Theobromine.

OTHER SYNTHETIC PRODUCTS.

(_Benzoic acid, camphor, adrenaline, salicylic acid._)

Certain chemical bodies which have been used in medicine for centuries have been analysed, their structural formulas ascertained, and then the atoms have been put together in the laboratory so perfectly that in many cases the artificial products cannot be distinguished from the natural original ones. Benzoic acid, obtained by subliming gum benzoin, has been in use since the latter part of the sixteenth century, when under the name of fleurs de benzoin, soon anglicised into flowers of benjamin, they were introduced by a French physician, named Blaise de Vigenère, who was secretary to Henri III. [The name benjamin was not a bad corruption after all, as the Arabic term from which the European designations were derived was Luban Jawa, the incense of Java. The Spaniards first dropped the first syllable under the mistaken impression that it was the Arabic article. Old etymologies traced the name to a supposed Ben-jui, or tree of the Jews.] The artificial benzoic acid is obtained by the oxidation of toluene, a hydrocarbon distilled from coal-tar.

Comparatively recent achievements of synthetic chemistry are the artificial production of camphor and of adrenaline, the active principle of the suprarenal gland. The synthetic products can be distinguished from the originals by their behaviour towards polarised light.

Salicylic acid, prepared by acting on carbolic acid by carbon dioxide in the presence of an alkali, became a practical commercial product in 1874, but its discoverer, Kolbe of Leipzig, had prepared it in his laboratory since 1859. The natural product, prepared from willow bark or oil of wintergreen, was worth twelve guineas a pound; the artificial salicylic acid in a few years came to be sold at not so many shillings per pound. Kolbe’s theory was that the compound he devised would decompose within the organism into phenol and carbon dioxide, and thus exercise an anti-putrefactive effect.

PHYSIOLOGICAL SPECULATIONS.

In many other cases the physiological effect of the compound was distinctly foreseen, and latterly the relation between chemical constitution and physiological action has become the objective of much research. It may be reasonably anticipated that before many years have passed it will be possible to predict the physiological powers of a substance from a knowledge of its structural formula, just as already many of its more noteworthy physical properties may be so foretold. Even at present certain trustworthy rules, affording guidance in this respect, have been formulated. Dujardin-Beaumetz and Bardel, dealing with compounds of the aromatic series, have laid down that (_a_) those containing hydroxyl (OH) are antiseptic; (_b_) those containing an amino-group (NH_{2}) or an acid amide are hypnotic; and (_c_) those containing both an amino-group and an alkyl group (CH_{3}, C_{2}H_{5}, etc.) are analgesic.

In order to show how synthetic remedies have been built up from simple products it will be convenient to take a few typical examples in the order of increasing chemical complexity, rather than with strict regard to chronological progression.

ALCOHOL, ETHER, ALDEHYDE, ACETIC ACID.

Ethyl (that is, ordinary) alcohol forms a convenient starting point. It has been already stated that the molecule of this substance is represented by the formula C_{2}H_{5}OH but for centuries before its constitution was unravelled it had been prepared in a more or less pure condition, as it still is, by a process of fermentation followed by distillation. Alcohol can be built up from its elements thus:--When an electric arc burns between carbon rods in an atmosphere of hydrogen, acetylene is formed; acetylene can be made to combine with hydrogen, forming ethane; ethane reacts with chlorine, yielding ethyl chloride; and this acted upon by an aqueous solution of potash gives alcohol as a result. The steps of the process are shown below:--

CH CH{3} CH{2}Cl CH{2}OH | --> | --> | --> | CH CH{3} CH{3} CH{3}

Acetylene. Ethane. Ethyl chloride. Ethyl alcohol.

Alcohol is the basis of a number of substances used in medicine. On treating it with a dehydrating agent such as strong sulphuric acid, the elements of water are removed, and two molecules of alcohol unite into one, the resulting product being ether (diethyl oxide). The reaction is rather more complicated than is explained here, but the net result is as stated. The process was described by the German physician, Valerius Cordus, and was incorporated in the “Dispensatory” published after his death by the Senate of Nuremberg, under the title of “Oleum vitriole dulce verum.” As explained in the article on Ether (Vol. I. p. 347), the chemical reaction was, until recent times, a favourite topic for investigation.

When alcohol (C_{2}H_{5}OH) is oxidised, a substance known as aldehyde (CH_{3}CHO) is formed. This was first prepared and described by Fourcroy and Döbereiner, but its constitution was explained by Kolbe. On further oxidation acetic acid (CH_{3}COOH) is formed. The relationship between the alcohol, aldehyde and acetic acid was traced by Liebig.

CHLORAL HYDRATE AND CHLOROFORM.

The oxidation of alcohol may be effected by the agency of chlorine, and in that case an intermediate oily product is obtained, in which three of the hydrogen atoms of the aldehyde are replaced by three of chlorine. The compound resulting is chloral (CCl_{3}CHO), and this readily combines with water and forms the familiar chloral hydrate crystals which were first prepared by Liebig in 1832, but only got into the “British Pharmacopœia” (Additions) in 1874. Chloral hydrate treated with caustic potash splits into chloroform and potassium formate. Chloroform was discovered in 1831 by Liebig and Soubeiran, and was admitted into the “London Pharmacopœia” of 1851, four years after Simpson had demonstrated its wonderful anæsthetic property.

SULPHONAL.

Returning to acetic acid, it may be stated that by heating its calcium salt two substances, acetone, (CH_{3})_{2}CO, and calcium carbonate are formed. Also that when alcohol is acted upon by phosphorus pentasulphide, mercaptan, C_{2}H_{5}SH, is obtained. By the reaction of acetone and mercaptan, mercaptol results, and this, when oxidised, becomes the well-known synthetic hypnotic, sulphonal. It is not necessary to give the full formulas of these reactions, as they may be found in the usual chemical manuals; but it may be stated that the full descriptive name of sulphonal is dimethyl-diethylsulphone-methane. The group of sulphones furnishes an illustration of the reasoning on which new synthetic compounds come to be constructed. The theory was that the physiological action of sulphonal was due to, or connected with, its ethyl group. It was supposed, therefore, that by increasing the number of such groups in a molecule the hypnotic effect would be proportionately developed. It was believed that experiments on dogs supported this deduction; but it was not maintained in clinical experience.

ACETANILIDE AND PHENACETIN.

Many of the popular synthetic remedies belong to the benzene series. Benzene is obtained from coal-tar, but, as shown by Berthelot, it is possible to prepare it by heating the gaseous hydrocarbon, acetylene, C_{2}H_{2}, in a closed vessel. By this means three molecules of acetylene are condensed into one, C_{6}H_{6}, which is benzene. Benzene acted upon by nitric acid yields nitrobenzene, and this by the action of nascent hydrogen is changed into aniline. Aniline may be regarded as ammonia, NH_{3}, in which one hydrogen atom has been replaced by the phenyl group, C_{6}H_{5}, and, like ammonia, it combines with acids to form salts. Aniline acetate being formed, the elements of water being eliminated in the process, the product is acetanilide, or antifebrin. Acetanilide was first prepared by Gerhardt, in 1853, but its physiological action was only discovered by Cahn and Hepp in the ’eighties. By the substitution of an ethoxy-group for one of the hydrogen atoms of acetanilide, para-ethoxy-acetanilide, commonly called “phenacetin,” is produced.

SALOL.

Phenol is another of the multitudes of substances obtainable from coal-tar; it can be prepared from aniline by the action of nitrous acid, and can be shown to be benzene with one hydrogen atom replaced by hydroxyl. If one of the adjacent hydrogen atoms of phenol is replaced by carboxyl, salicylic acid is produced; and in the presence of a suitable dehydrating agent salicylic acid reacts with phenol and phenyl salicylate, known as salol, is formed.

ANTIPYRIN.

Many of the synthetic chemicals are much more complex than those so far described. They are built up on similar lines, but the processes involve a greater number of stages. Antipyrin (phenazone, or phenyl-dimethylisopyrazolone) may be added to the examples selected for this notice. Antipyrin is represented by the annexed formula, which is said to be heterocyclic,

H{3}CC-----CH | | H{3}CN CO \ / \ / N | C{6}H{5}

because its molecules, like those of pyridine, consist of rings not made up exclusively of carbon atoms.

* * * * *

It must be understood that in this sketch only a very few notable instances of modern chemical research have been given, these being some of the more familiar products which have been introduced into medicine. Favourite colours, odours, and flavours have likewise been synthesised, and the manufacture of some of these artificial products has developed into vast businesses. The object of this chapter has been to make it clear that the marvellous activity which has been displayed in these directions during the past half-century, has been guided by the most profound and skilful research, one step leading to another, and that the new products have not been hit upon by mere chance.

XXIV

NAMES AND SYMBOLS

“Every trade and handicraft, every art, every science, is constantly changing its materials, its processes, and its products; and its technical dialect is modified accordingly, while so much of the results of this change as affects or interests the general public finds its way into the familiar speech of everybody.” (W. DWIGHT WHITNEY:--“Language and its Study.” 1876.)

The technological vocabulary of pharmacy is very voluminous, and has been recruited from all languages. Many of the names of vegetable drugs literally household words in English, have been transferred direct from savage tongues. Guaiacum, ipecacuanha, and jalap may be cited as examples. Other names of drugs cover histories which well repay investigation.

Take, for example, the word hyoscyamus and its English equivalent henbane (which I select because it does not happen to be alluded to elsewhere in this work). The obvious and usual explanation of these names is that hyoscyamus is the Greek genitive hyos, of a hog, and kyamos, a bean, and in fact the name of hog’s bean is applied to it in several languages. Henbane, too, is supposed to be self-explanatory. But there is good reason to believe that neither of these interpretations is correct. Dioscorides, who calls the plant hyoscyamos, also mentions that its almost obsolete name was dioskyamos; and henbane is well known to be a corruption of henne-bell. The obsolete name is obviously more likely to convey the original meaning than its corruption, and therefore hyoscyamos is more likely to have meant the bean of the gods than the bean of the pigs. Possibly its name was traceable to the idea that the delirium which the drug produced was the condition induced in human beings when the gods communicated with them, or that some priests used it to produce that condition in which messages presumably from the higher powers could be transmitted. Henbane, again, is not satisfactorily accounted for by its surface meaning. There is no evidence that hens ever eat the herb or the seeds. But the Saxon name henne-bell suggests some sort of a musical instrument, and it is a curious fact that in mediæval Latin henbane was sometimes known as Symphoniaca Herba; the Symphoniaca being a rod with a number of little bells on it. This description might be appropriately applied to the plant, and we have only to suppose a Saxon term “hengebelle” to clear up the mystery.

I am indebted for the foregoing notes to three very suggestive articles in _The Chemist and Druggist_ of October and November, 1877, and February, 1878, by Mr. W. G. Piper.

Next we come to the fanciful and poetic names of metals and their salts, and of all sorts of chemical compounds, invented by the alchemists. They gave the names of aquila alba, mercurius dulcis, panchymagogum minerale, manna metallorum, draco mitigatus, and others to calomel; regulus, or the little king, to antimony (gold being king); lunar caustic, ethiops martial, and salts of Saturn; vitriol, tartar, pompholix, and scores of others, not selected without judgment, but intended rather to mystify the public than to instruct them.

Chemical nomenclature of the present day has gone to the opposite extreme. The ingenious laboratory devisers of synthetic products have developed a nomenclature which it is impossible to use. It explains itself to the initiated, but even for intercommunication between chemists, pharmacists, and physicians words like tetrahydroparamethyloxyquinoline or calcium betanaphthol-alphamonosulphonate insist on being simplified if the substances they describe come into medicinal use; and to do them justice it must be admitted that the inventors of the products are always ready to meet this requirement with a more or less expressive title which can be protected as a trade mark. This forces other manufacturers to devise other distinct names for the same article, so that among the new chemicals which have become popular within the past thirty years there are sometimes a dozen designations for the same substance.

A PHARMACEUTICAL VOCABULARY.

The subjoined list of technical terms is limited to the names of pharmaceutical processes, products, and apparatus; and only (as a rule, with some exceptions) of such as are not dealt with in other sections. Many of the terms are obsolete, but are to be met with in old treatises. Occasionally rather more than a bare definition has been thought desirable.

* * * * *

Acetabulum. Originally a vessel used by the Romans for holding vinegar at the table. Then a liquid measure about 2½ oz.

Acetum Philosophicum. Vinegar made from honey.

Acopon. A stimulating or anodyne liniment, almost of the consistence of an ointment. If acopa contained aromatics they were called myracopa.

Adept. An alchemist who “had attained.”

Adust. A dried up condition of the humours.

Aggregatives. Pills devised by Mesué which were intended to purge all the humours.

Alabaster. A special kind of carbonate or sulphate of lime used by the ancients for ointment containers which were sometimes called alabastra. The name is supposed to have been derived from a town in Egypt.

Album Rhasis. White lead ointment, which Rhazes was believed to have introduced.

Alembic. The Arabic name for a still. It was adapted by the Arabs from the Greek ambix, a vase, to which was prefixed the particle al. The word became corrupted in English to Limbeck.

Alembroth. Sal Alembroth was the double chloride of mercury and ammonium. Also called the salt of wisdom. The word has not been traced, but has been supposed to be a Chaldaic term meaning the key of art.

Alexipharmic (in Greek alexipharmakon). A remedy against poison.

Alexiteria. Remedies against the bites of venomous animals.

Alhandal. The Arabic name for colocynth which was applied to certain lozenges or tablets of that drug.

Alkahest. The universal solvent, or menstruum. The word has an Arabic appearance, but cannot be traced to that language. It is believed to have been one of Paracelsus’s many etymological inventions. The derivation has been guessed to have been from the German al-geist, all spirit, Paracelsus said it was a liquid to cure all kinds of engorgements. Van Helmont’s Alkahest was capable of restoring to their first life all the bodies of nature. Glauber’s Alkahest was nitrate potash which had been detonated on live coals. It was carbonate of potash.

Alkali, in Arabic al-qaly. Qaly meant to fry, and the technical term was applied to the ashes of plants after frying or roasting.

Alkekengi. The Winter Cherry, formerly in much esteem as a remedy in kidney and urinary complaints.

Alkool. This name was given to powders of the finest tenuity. It was also applied to spirit of wine rectified to the utmost extent. Boerhaave employed the term to indicate the purest inflammable principle.

Aloedarium. A purgative medicine with aloes as the principal ingredient.

Aludels. Pear-shaped pots constructed so that they could be fitted one into another, a series of them being used for sublimations. The name is supposed to have had an Arabic origin, or it may have meant “not luted.”

Amalgam. A compound of mercury and some other metal. Believed to have been a perversion of malagma, a soft ointment, with the Arabic article prefixed.

Amphora. An earthenware vessel with two handles wherewith to carry it. Used by the Greeks and Romans for wine and oil. The Greek vessel contained about 9 gallons; the Roman amphora was equivalent to nearly 7 gallons.

Analeptica. Restorative remedies.

Anoyntment. An old term for ointment.

Antidotary. A frequent title of books of formulas for medicines.

Antidote. Something “given against.” Originally, perhaps, an adjective, and in old medicine employed for various remedies; now limited to substances which will counteract the effect of poisons.

Apozems. Strong decoctions or infusions. A Greek word meaning “boiled off.”

Aqua Mirabilis. Once a popular household remedy. Water distilled from cloves, cardamoms, cubebs, mace, ginger, and other spices.

Aquila Alba. An old name for calomel.

Arcana meant secrets. The original idea of the word was things shut up and protected as the occupants of Noah’s Ark were shut up. The alchemists used the word arcanum freely, but it came to be applied to medicines of known composition but of mysterious action. Arcanum tartari was acetate of potash. Arcanum duplicatum was another name for the Sal de Duobus or sulphate of potash which was supposed to combine the virtues of nitre and vitriol.

Athanor was a self-supplying furnace, the coals or fuel being provided in a reservoir above the fire and intended to be supplied to the furnace automatically.

Balm and Balsam, which are words with the same origin, have always been suggestive of medicinal and healing virtues. Probably balsam has descended through the Greek and Latin from Semitic terms meaning spices. The Hebrew Besem or Bosem, often translated “spices,” in one place “cinnamon,” in another “calamus,” always meant some grateful aromatic. But the opobalsamum or juice of the Balsam tree, the famous Balm of Gilead, was Tsori in Hebrew. Old etymologists, supported by Littré and other moderns, consider that Baal-schaman, prince of oils, was the original word from which balsam was derived. The Arabic Abu-scham, father of perfumed oils, was a name for the balsam tree. Paracelsus taught that the human body contained a natural balsam which tended by itself to heal wounds.