The Breakdown of Vitalism
Ever since the discovery of fire, mankind was bound inevitably to divide substances into two classes; those that burned and those that did not. The principle fuels in early times were wood and fat or oil. Wood was a product of the plant world, while fat and oil were products of both the animal and plant world. For the most part, materials of the mineral world, such as water, sand, and the various rocks, did not burn. They tended, rather, to put out fire.
It was not hard to see, then, that the two classes of substances, combustible and non-combustible, might be considered, just as conveniently, as those which arose only from living things, and those which did not. (Of course, exceptions are to be found to this rule. Coal and sulfur, which seem products of the non-living body of the earth, are combustible.)
The accumulating knowledge of the eighteenth century showed chemists that the mere fact of combustibility was not all that divided the products of life from those of non-life. The substances characteristic of the non-living environment could withstand harsh treatment, whereas the substances originating from living or once-living matter could not. Water might be boiled and recondensed to water; iron or salt could by melted and re-frozen into the unchanged original. Olive oil or sugar, however, if heated (even under conditions that prevented burning), proceeded to fume, smoke, and char. What was left was not olive oil or sugar, nor could olive oil or sugar be formed out of it once more.
The difference seemed fundamental, and, in 1807, Berzelius suggested that substances like olive oil or sugar, the characteristic products of organisms, be called organic. Substances like water or salt, characteristic of the non-living environment, were inorganic.
A point that did not fail to impress chemists was that organic substances were easily converted, by heating or other harsh treatment, into inorganic substances. The reverse change, from inorganic to organic, was, however, unknown, at least as the nineteenth century opened.
Many chemists, at that time, considered life a special phenomenon that did not necessarily obey the laws of the universe as they applied to inanimate objects. A belief in this special position of life is called vitalism, and it had been strongly preached, a century earlier, by Stahl, the inventor of phlogiston. In the light of vitalism, it seemed reasonable to suppose that some special influence (a "vital force"), operating only within living tissue, was required to convert inorganic materials into organic ones. Chemists, working with ordinary substances and techniques and without being able to manipulate a vital force in their test tubes, could not bring about this conversion.
It was for this reason, men argued, that inorganic substances might be found anywhere; in the realm of life and in that of non-life as well, as water might be found in both the ocean and the blood. Organic substances, requiring the vital force, would be found only in connection with life.
This view was first disrupted in 1828 by the work of Friedrich Wohler (1800-1882), a German chemist, who had been a pupil of Berzelius. Wohler was particularly interested in cyanides and related compounds, and was engaged in heating a compound called ammonium cyanate. (This was widely regarded, at the time, as an inorganic substance, having no connection with living matter in any way). In the course of the heating, Wohler discovered he was forming crystals that resembled those of urea, a waste product eliminated in considerable quantity in the urine of many animals, including man. Closer study showed the crystals were undoubtedly urea, which was, of course, clearly an organic compound.
Wohler repeated the experiment a number of times and found that he could convert an inorganic substance (ammonium cyanate) to an organic substance (urea) at will. He communicated this discovery to Berzelius, and that hard-headed man (who rarely condescended to be budged out of his opinions) was forced to agree that the line he had drawn between the inorganic and the organic was not as tight as he had thought.
The importance of Wohler's feat should not be overestimated. In itself, it was not very significant. There were grounds for arguing that ammonium cyanate was not truly inorganic and, even if it were, the change over from ammonium cyanate to urea (as was eventually made clear) was merely the result of an alteration of the positions of the atoms within the molecule. The molecule of urea was not, in any real sense, built up of a completely different substance.
Yet neither should Wohler's feat be dismissed. If it was, in truth, a minor item it itself, it nevertheless served to break down the hold of vitalism over the minds of men. (Actually, this was only an initial defeat for vitalism, which maintained its hold in other areas of chemistry. Despite a slow weakening of its position throughout the nineteenth century, vitalism is not entirely dead even now). It served to encourage chemists to attempt the synthesis of organic substances where otherwise they might have turned their efforts in other directions.
In 1845, for instance, Adolph Wilhelm Hermann Kolbe (1818-1884), a pupil of Wohler's, succeeded in synthesizing acetic acid, an indubitably organic substance. Furthermore, he synthesized it by a method which showed that a clear line of chemical change could be drawn from the constituent elements, carbon, hydrogen, and oxygen, to the final product, acetic acid. This synthesis from the elements or total synthesis is all that can be asked of the chemist. If Wohler's synthesis of urea did not settle the matter of the vital force, Kolbe's synthesis of acetic acid did.
Carrying matters further was the French chemist Pierre Eugene Marcelin Berthelot (1827-1907). During the 1850's, he went about the synthesis of organic compounds systematically, turning them out in scores. These included such well-known and important substances as methyl alcohol, ethyl alcohol, methane, benzene, and acetylene. With Berthelot, crossing the line from inorganic to organic ceased to be a thrilling intrusion upon the "forbidden", and became purely routine.
The Building Blocks of Life
But the organic compounds formed by Wohler, Kolbe, and Berthelot were all relatively simple. More characteristic of life were the far more complex substances such as starch, fats, and proteins. These were less easy to manipulate; their exact elementary makeup was less easy to determine; and on the whole they presented the budding realm of organic chemistry with a truly formidable problem.
All that could be said about them at first was that these complex substances could be broken down to relatively simple "building blocks" by heating them with dilute acid or dilute base. Russian chemist, Gottlieb Sigismund Kirchhoff (1764-1833), was the pioneer in this respect. In 1812, he succeeded in converting starch (by heating it with acid) to a single sugar which was eventually named glucose.
In 1820, the French chemist Henri Braconnot treated the protein gelatin in the same fashion, and obtained the simple compound glycine. This was a nitrogen-containing organic acid belonging to a group of substances eventually named (by Berzelius) amino acids. Glycine itself proved merely the forerunner of some twenty different amino acids, all which were isolated from naturally occurring proteins over the next century.
Both starch and protein possess giant molecules that are made up (it eventually was learned) of long strings of glucose units and of amino acid units, respectively. The chemists of the nineteenth century could do little in the way of putting such long strings together in the laboratory. The case was otherwise with fats.
The French chemist Michel Eugene Chevreul (1786-1889) spent the first part of an incredibly long professional life in an investigation of fats. In 1809, he treated soap (manufactured by heating fat with alkali) with acid, and isolated what are now called fatty acids. Later, he showed that when fats are converted to soap, glycerol is removed from the fat.
Glycerol possesses a comparatively simple molecule upon which there are three logical points of attachment for additional atom groups. By the 1840's, therefore, it seemed quite logical to suppose that while starch and protein might be made up of very many simple units, the case was otherwise with fats. Fats might be made up of just four units, one glycerol plus three fatty acids.
Berthelot stepped in here. In 1854, he heated glycerol with stearic acid, one of the more common fatty acids obtained from fats. He found that he did produce a molecule made up of a glycerol unit united to three stearic acid units. This was tristearin, and proved to be identical with tristearin obtained from natural fats. This was the most complicated natural product to be synthesized up to that time.
Berthelot went on to take an even more dramatic step. In place of stearic acid, he took acids that were similar but which were not obtained from natural fats themselves. These acids he heated with glycerol and obtained substances very much like ordinary fats, but not quite like any of the fats known to occur in nature.
This synthesis showed that the chemist could do more than merely duplicate the products of living tissue. (The chemist has not actually duplicated the more complex products of living tissue even today. However, it is generally accepted that the duplication of even the most complex molecule is possible in principle; it is only time and effort that need by applied - in some cases, to be sure, a prohibitive amount of time and effort.) He could go beyond and prepare compounds that were like organic compounds in all their properties, but that were not like any organic compound actually produced by living tissue. The second half of the nineteenth century was to carry this aspect of organic chemistry to dramatic heights indeed.
It is no wonder that by the mid-nineteenth century the division of compounds into organic and inorganic on the basis of the activity of living tissue had become obsolete. Organic compounds existed that had never been manufactured by an organism. Nevertheless, the division was still useful, for there remained important distinctions between the two classes. The distinctions were so important that the chemical techniques of the organic chemist seemed completely different from those of the inorganic chemist.
More and more it came to seem that the difference lay in chemical structure, for there two completely different kinds of molecules seemed to be involved. Most of the inorganic substances dealt with by the nineteenth-century chemist possessed small molecules made up of two to eight atoms. There were very few inorganic molecules of consequence with as many as a dozen atoms.
Even the simpler organic substances had molecules made up of a dozen atoms or more; often several dozen. As for substances such as starch and protein, they possessed, literally, giant molecules which could count their atoms by the thousands and even hundreds of thousands.
It is no wonder, then, that the complex organic molecule could easily and irreversibly be broken down even by mild disrupting influences such as gentle heat, while the simple inorganic molecules held firm under even harsh conditions.
Then, too, it became increasingly worthy of note that all organic substances, without exception, contained one or more atoms of carbon in their molecules. Almost all contained hydrogen atoms as well. Since carbon and hydrogen are themselves inflammable, it is not unexpected that compounds of which they form so important a part are also inflammable.
The German chemist Friedrich August Kekule von Stradonitz (1829-1886), usually referred to simply as Kekule, took the logical step. In a textbook published in 1861, he defined organic chemistry as merely the chemistry of carbon compounds. Inorganic chemistry was then the chemistry of compounds that did not contain carbon. This definition has been generally accepted. It remains true, however, that a few carbon compounds, among them carbon dioxide and calcium carbonate, resemble the typical inorganic compound more than they do the typical organic compound. Such carbon compounds are usually treated at length in books on inorganic chemistry.
Isomers and Radicals
The simple inorganic compounds involved in the great chemical advances of the eighteenth century had easily been interpreted in atomic terms. It seemed quite sufficient to indicate the different types of atoms present in each molecule and the number of each. One could write the oxygen molecule as O2, hydrogen chloride as HCl, ammonia as NH3, sodium sulfate as Na2SO4, and so on.
Such formulas, giving nothing more than the number of each type of atom present in the molecule, are called empirical formulas. (The word "empirical" means "determined by experiment".) It was natural to feel, in the first decades of the nineteenth century, that each different compound had a distinct empirical formula of its own and that no two compounds could have the same empirical formula.
Organic substances, with their large molecules, were troublesome from the start. The empirical formula of morphine (quite a simple organic compound as compared with proteins, for instance) is now known to be C17H20NO3. It would have been most difficult, using early nineteenth-century techniques, perhaps even impossible, to decide whether that or, say, C16H20NO3, were correct. The empirical formula of acetic acid, much simpler (C2H4O2) than that of morphine, aroused considerable controversy in the first half of the nineteenth century. Nevertheless, if chemists were to learn anything about the molecular structure of organic substances, they had to start with empirical formulas.
In the 1780's, Lavoisier had tried to determine the relative proportions of carbon and hydrogen in organic compounds by burning them and weighing the carbon dioxide and water produced. His results had not been very accurate. In the first years of the nineteenth century, Gay-Lussac (discoverer of the law of combining volumes) and his colleague, the French chemist Louis Jacques Thenard (1777-1857), introduced an improvement. They mixed the organic substance with an oxidizing agent, such as potassium chlorate. On heating, this combination yielded oxygen, and the oxygen, intimately mixed with the organic substance, brought about its more rapid and complete combustion. By collecting the carbon dioxide and water formed on combustion, Gay-Lussac and Thenard could determine the relative proportion of carbon and hydrogen in the organic compound. With Dalton's theory now advanced, this proportion could be expressed in atomic terms.
Many organic compounds were made up only of carbon, hydrogen, and oxygen. With carbon and hydrogen determined and oxygen assumed to account for whatever was left over, an empirical formula could often be worked out. By 1811, Gay-Lussac had worked out the empirical formulas for some of the simple sugars, for instance.
This procedure was improved further by a German chemist, Justus von Liebig (1803-1873) who, by 1831, could obtain fairly reliable empirical formulas as a result. (Liebig was one of the great chemistry teachers of all time. He taught at the University of Giessen, where he established the first real laboratory course in chemistry. Numerous chemists studied with him and learned laboratory procedures from him. Liebig was one of the influences making chemistry, in which France had been pre-eminent in the eighteenth century, almost a German monopoly in the nineteenth century.) Soon afterward, in 1833, the French chemist Jean Baptiste Andre Dumas (1800-1884) devised a modification of the method, one which allowed the chemist to collect nitrogen also among the products of combustion. In this way one could determine the proportions of nitrogen in an organic substance.
These pioneers in organic analysis, in the course of their researches, produced results that shattered the belief in the importance of the empirical formula. It came about this way:
In 1824, Liebig studied a group of compounds, the fulminates, while Wohler (who was to become a fast friend of Liebig, and who was soon to synthesis urea) was studying another group of compounds, the cyanates. Both sent reports concerning their work to a journal edit by Gay-Lussac.
Gay-Lussac noted that the empirical formulas given for these compounds were identical, and yet the properties described were quite different. (As an example, both silver cyanate and silver fulminate consist of molecules containing one atom each of silver, carbon, nitrogen, and oxygen).
Gay-Lussac reported this observation to Berzelius, then the most noted chemist in the world, but Berzelius was reluctant to believe the discovery. By 1830, however, Berzelius himself had discovered that two organic compounds, racemic acid and tartaric acid, although possessing different properties, seemed to have the same empirical formula (now know to be C4H6O6).
Since elements were present in these different compounds in the same proportions, Berzelius suggested that such compounds be termed isomers (from Greek words meaning "equal proportions"), and the suggestion was adopted. In succeeding decades, more and more cases of isomerism were discovered.
It seemed clear that if two molecules were made up of the same number of the same kinds of atoms and yet were different in properties, the difference must lie in the manner in which the atoms were arranged within the molecule. In the case of the simple molecules of the better-known inorganic compounds, it might be that only one arrangement of the atoms within the molecule was possible. For that reason, no isomers would arise and the empirical formula would be sufficient. Thus, H2O would be water and nothing else.
In the more complicated organic molecules, however, there would be room for different arrangements and, therefore, for isomers. In the case of the cyanates and fulminates, the different arrangements are easy to discover, for each molecule contains but a few atoms. Silver cyanate can be written AgOCN, while silver fulminate is AgNCO.
Here only four atoms are involved. With still more atoms, the number of possible arrangements become so great that it is difficult indeed to decide just which arrangements fit which compounds. Even the case of racemic acid and tartaric acid, with sixteen atoms to the molecule, was too difficult to handle in the first half of the nineteenth century. The situation would grow simply impossible (so it might have seemed) if still larger molecules were considered.
The problem of molecular structure might have had to be abandoned as hopeless almost as soon as the very existence of the problem had been recognized, had not a possibility of simplification appeared.
In 1810 and thereafter, Gay-Lussac and Thenard were working with hydrogen cyanide (HCN), which they showed to be an acid, although it didn't contain oxygen. (This, like Davy's nearly simultaneous discovery of the same fact concerning hydrochloric acid - disproved Lavoisier's belief that oxygen was the characteristic element of acids.) Gay-Lussac and Thenard found that the CN combination (the cyanide group) could be shifted from compound to compound, without its breaking apart into individual carbon and nitrogen atoms. The CN combination, in fact, acted much as a single atom of chlorine or bromine might act, so that sodium cyanide (NaCN) had some properties in common with sodium chloride (NaCl) and sodium bromide (NaBr). ("Some Properties" does not, most emphatically, mean all properties. Sodium Chloride is essential to life, sodium bromide has mild toxic effects, and sodium cyanide is a virulent, fast-acting poison.)
Such a group of two (or more) atoms that remain in combination while being shifted from one molecule to another was termed a radical, from the Latin word for "root". The reason for the name was that molecules, it was believed, might be built up of a limited number of small atom combinations. The radicals would then be the "roots" out of which the molecule would, so to speak, grow.
Of course, the CN group was a very simple one, but a considerably more complex cas was demonstrated by Wohler and Liebig, working together. They discovered that the benzoyl group cold be switched from one molecule to another without being disrupted. The empirical formula for the benzoyl group is now known to be C7H5O.
In short, it began to appear that to solve the structural mystery of large molecules, one must first solve the structures of a certain number of different radicals. The molecules could then be constructed, without much difficulty (it was hoped), out of the radicals.