Air 1 1_History of Chemistry, Volume 2 (of 2) From 1850 to 1910

Hydrogen 0.276 0.263

Marsh gas 0.753 0.745

Ethylene 0.987 0.985

Nitrogen 0.986 0.986

Oxygen 1.053 1.051

Carbon dioxide 1.203 1.237

Nitrogen and ethylene are, chemically, totally dissimilar gases, but

they have the same density and hence the same rate of movement. As

Graham showed, it is possible to separate more or less completely a

mixture of gases, if the constituents are of different densities,

by taking advantage of their different rates of movement. Such an

_atmolytic_ method was employed by Rayleigh and Ramsay to prove that

atmospheric nitrogen contained argon.

The fact that all gaseous substances, however different their chemical

nature, conform in the main to certain simple “laws” indicates

the probability that their mechanical structure is similar and

comparatively simple. The so-called gaseous “laws”—the laws of Boyle,

Dalton, Gay Lussac, Avogadro, and Graham—are to-day explained on

the assumption that a gas consists of an aggregation of molecules,

moving incessantly in straight lines and with great rapidity. The

rate of movement of the particles is variable by reason of their

mutual encounters; at the same instant some are moving rapidly, others

more slowly. As already explained, to this ceaseless movement of the

molecules is to be ascribed the pressure they exert; the pressure which

a gas exerts on any containing surface is the aggregate effect of the

impact of its molecules. The law of Boyle states that the product of

the volume V and pressure P of a given mass of gas is invariable so

long as the temperature is unchanged: PV = constant. It was found

by Regnault, Magnus, Natterer, and Amagat that all gases, with the

exception of hydrogen, show a departure from Boyle’s law in the sense

that PV is less than theory demands. In the case of hydrogen PV is

greater than theory. This exception, however, is only apparent. Every

gas, if maintained above a certain temperature, shows, after a certain

pressure has been reached, a deviation in the same sense as that

exhibited by hydrogen.

The deviations from Boyle’s law are probably due to two causes: (1) to

the effect of cohesion among the molecules, whereby the volume, and

hence PV, is less than theory requires; (2) the molecules are not

mathematical points—they have a certain volume; hence, with increasing

pressure, PV is greater than theory demands. The effect of the molecule

having a certain magnitude will be clear from the following figure: Let

M be a molecule moving backwards and forwards within a certain space,

_a b_:

| M |

_a_ | | _b_

| • |

| |

Assume, now, we halve the containing space:

| M |

_a_ | | _b_

| • |

| |

It will be seen that M, since its volume is unchanged, will have less

than half the original distance to travel or, in other words, it

will strike the boundaries of the containing space _more_ than twice

as frequently in the same interval of time as before; hence P, and

therefore PV, becomes greater than Boyle’s law demands.

It will be noticed, then, that the two causes tending to bring

about deviations from Boyle’s law act in contrary directions. In

the greater number of gases the effect due to cohesion at ordinary

pressure is greater than the effect due to the actual space occupied

by the molecules. In the case of hydrogen at ordinary temperature the

contrary is the case; if, however, hydrogen is strongly cooled, it

shows variations similar to those exhibited by other gases at ordinary

temperatures. By heating these gases the effect due to cohesion—to

the mutual attraction of the molecules—becomes less and less; in such

circumstances these gases show departures from theory in the same sense

that hydrogen does at ordinary temperatures.

The effect of mutual attraction among the molecules is to make the

volume of the gas less than the theoretical value; the cohesive force

may therefore be regarded as equal in effect to a certain additional

pressure; that is, (P + A) V = constant, in which A is the measure of

the force of cohesion. A, of course, must have relation to the number

of molecules mutually attracted: _A is proportional to the square of

the number of the molecules_. But the number of the molecules in the

unit volume is proportional to the density of the gas, and in a given

mass of gas the density is inversely proportional to the volume. Hence

A is inversely proportional to the square of the volume—A = _a_/V2,

hence (P + _a_/V2) V = constant. Now let us trace the effect of the

second cause of variation from the mathematical exactitude of Boyle’s

law. The fact that the molecules are not mathematical points means that

V in the foregoing expression is not identical with the space in which

the molecules move. That space is V - _b_, in which _b_ is the measure

of the aggregate volume of the molecules. Hence the true expression

becomes (P + _a_/V2) (V - _b_) = constant.

The law of Dalton (Charles) also receives its simplest explanation by

the kinetic theory of gases; and, moreover, the departures from the

mathematical truth of the statement follow as a necessary consequence

of the facts that the molecules have sensible magnitudes and are

mutually attracted. We can measure the effect of heat upon a gas

in two ways. We can either keep the pressure of the gas constant,

and measure the increase in volume; or we can prevent the gas from

expanding, and measure the elastic force or pressure it exerts. If the

law of Dalton were mathematically true, it would follow that, _if the

volume of the gas were maintained constant during the heating, its

pressure would increase in the same proportion as the volume would have

increased if the gas had been allowed to expand, but maintained at a

constant pressure_. In other words, the expansion-coefficient and the

pressure-coefficient should be the same. Experiment shows, however,

that they are not identical.

The following table gives the results of a number of measurements by

Regnault:

_Expansion _Pressure

(Pressure (Volume

Constant)._ Constant)._

Hydrogen .003661 .003667

Air .003670 .003665

Carbon dioxide .003710 .003688

Sulphur dioxide .003903 .003845

Variations in the same sense have since been observed by Jolly and

Chappuis. With the exception of hydrogen, and probably also helium, all

the gases show greater values for the coefficient of expansion than

for the coefficient of pressure, and the differences are greater the

greater the coefficient of expansion of the gas.

Since, as we have already stated, the law of Boyle is directly related

to the law of Dalton, both being dependent on molecular movements, the

same course of reasoning used to account for the variations in the case

of Boyle’s law applies equally to the case of Dalton’s law. The “law”

of Avogadro follows also as a necessary consequence of this explanation

of the laws of gaseous pressure and temperature. If all gases show

approximately the same increase in pressure when heated under constant

volume, and if the increased pressure is due only to the increased

energy with which the molecules strike the sides of the containing

vessel, it follows that all gases must contain the same number of

molecules in unit volume. But as, from the very nature of the case, the

laws of Boyle and Dalton cannot be mathematically true, it follows that

the laws of Avogadro and Gay Lussac must be only approximations in the

same sense.

The law of Graham, connecting the rate of diffusion of a gas with its

density, follows also as a necessary consequence of this explanation

of the laws of Boyle, Dalton, Gay Lussac, and Avogadro. If the number

of molecules in the unit volume of any gas, whatever be its nature and

whatever be their mass, is approximately the same, it follows that the

mean velocity of the molecules must be variable; their mean velocities

must be in the inverse ratio of the square roots of their densities.

The mean velocity with which the molecules of a gas move can be

calculated if we know the pressure it exerts, the weight of a definite

volume, and the value of the acceleration due to gravity. The square

of this velocity in metres per second of time at 0°C. is given by the

expression U² = 3_pg_/_q_ in which _p_ = pressure per square metre =

10,333 kilograms; _g_ = the gravitation constant = 9.81; _q_ = weight

of a cubic metre of the gas at 0°C. and one atmosphere of pressure.

For hydrogen we have

U² = 3 × 10,333 × 9.81/0.0899

whence U = 1842 metres per second; for oxygen we have U² = 3 × 10,333

× 9.81/1.430, whence U = 461. These numbers accord with those demanded

by Graham’s law. The density of H being taken as 1, that of oxygen is

16 and √16 = 4; the numbers 1842 and 461 are in the ratio of 4 to 1.

The amount of heat required to raise the temperature of the unit mass

of a gas through a definite interval depends, as Laplace first pointed

out, upon whether the gas is allowed to expand or not; in other words,

the specific heat of a gas varies as the heating is at constant volume

or at constant pressure. If, having raised the temperature of the unit

mass, and so expanded it, we then compress it until it occupies its

initial volume, a further rise of temperature takes place without any

external heat having been applied. This rise of temperature is, in

fact, due to the liberation of the amount of heat required merely to

expand the gas without increasing its temperature. The quantity of heat

needed to raise the temperature of a gas through a definite interval is

therefore greater when it is allowed to expand than when its volume is

kept constant; in other words, the specific heat at constant pressure

is greater than the specific heat at constant volume. The ratio of

the two specific heats can be calculated: on the assumption that

the energy imparted to the molecules simply accelerates their mean

rectilinear velocity, and that no energy is absorbed in doing internal

work among them, it is found that, when the gas is permitted to expand,

the amount of heat required is 1.67 times greater than that needed

when its volume is kept constant. This ratio has been experimentally

determined for a number of gases. For oxygen under normal conditions it

is 1.408, for hydrogen 1.414, for carbon dioxide 1.264, for methane

1.269—all numbers notably below the value 1.67. The direct experimental

determination of this ratio by thermometric measurements is a matter of

some difficulty. It was, however, demonstrated by Dulong that it can

be ascertained with comparative ease from observations on the velocity

of sound in the gas—the velocity being probably a direct function of

this ratio. As carried out experimentally, the method consists in

sending a sound-wave through the gas contained in a glass tube along

the horizontal length of which is strewn a quantity of a light powder

such as the spores of lycopodium or finely divided silica. The glass

tube is fitted at one end with a glass rod; by rubbing this a series

of longitudinal vibrations is set up and communicated to the gas

whereby the light powder is thrown up into little heaps along the tube,

the distance between the heaps being equal to half a wave length. By

comparative measurements with air and the gas under examination, data

are obtained from which the ratio of the specific heats can be deduced.

By experiments conducted on this principle Kundt and Warburg found that

mercury vapour gave numbers agreeing with the theoretical ratio 1.67.

Now, its vapour density shows that mercury vapour is a monatomic gas;

it actually fulfils the conditions prescribed for a gas which theory

indicates should give the value 1.67. All the energy imparted to its

molecules on heating simply accelerates their translational velocity.

On the other hand, all the gases above named as giving values below

1.67 are diatomic gases; in their case the energy imparted to them

is employed partly in augmenting the translational velocity of the

molecules, and partly in bringing about internal changes within them.

By experiments made in like manner Ramsay and Travers succeeded in

showing that the inert gases of the atmosphere are monatomic.

No attempt can be made here to explain the various methods by which

it has been sought to obtain an estimate of the absolute size of

gaseous molecules or to determine their number in a definite volume. By

observations on their viscosity, rates of diffusion, conductivity for

heat, variations from the law of Boyle, dielectric constants, electric

charges, etc., Maxwell, O. E. Meyer, Loschmidt, Lothar Meyer, Van der

Waals, Mossotti, Planck, Sir J. J. Thomson, and others, have arrived

at estimates of the magnitude and number of molecules in a gas. These

estimates necessarily vary with the hypotheses made in deducing them.

It would serve no useful purpose to give the results, since the figures

convey no impression to the mind of the minuteness of molecules, or

even as to the extraordinary number of them in, say, so small a volume

as one cubic centimetre. As an example, it has been calculated that

there are about 640 trillions of hydrogen molecules in one milligram of

the gas.[3]

[3] O. E. Meyer, _The Kinetic Theory of Gases_, 1899.

* * * * *

In the preceding volume a short account has been given of the history

of the early attempts to effect the liquefaction of the gases. These

resulted in their division into the two classes of _liquefiable_ and

_permanent_ gases. One of the most notable achievements of the latter

half of the last century was to sweep away this arbitrary distinction.

The fundamental condition needed to effect the liquefaction of a

gas, although surmised by Faraday, was first clearly indicated by

Andrews about 1863. He showed that, in order to liquefy a gas, its

temperature must be lowered to a point peculiar to each gas, when, on

the application of sufficient pressure, it will become a liquid. Thus,

in the case of gaseous carbon dioxide, Andrews found that, if its

temperature were maintained above 31° C., no amount of pressure would

cause it to liquefy; if the temperature were lowered just below this

point—termed the _critical point_—a pressure of 75 atmospheres would

effect its liquefaction. On the other hand, if the temperature of the

liquid carbon dioxide be slowly raised to about 31°, the surface of

demarcation between the liquid and the gas becomes gradually fainter

and eventually disappears. Carbon dioxide may thus be made to pass

from the state of liquid to that of gas without any sudden alteration

of volume. If a given volume of the gas, say at 50°, be exposed to

gradually increasing pressure, say up to 150 atmospheres, the volume

is gradually diminished with the increment of pressure, but no sudden

contraction indicating liquefaction occurs. If the gas under the high

pressure be allowed to cool down to the ordinary temperature, no

sudden contraction is observed to follow. The carbon dioxide, at the

outset a gas, in the end becomes a liquid by a gradual and continuous

transition, unaccompanied by any abrupt change of volume. These

observations show that what we style the liquid and gaseous states

are simply separated manifestations of the same condition of matter.

There is a definite temperature for every gaseous substance at which it

ceases to be liquefiable under pressure; and the reason that Faraday

failed to liquefy certain gases was that he was unable, with the means

at his command, to lower their temperatures sufficiently and so reach

their critical points; hence the enormous pressures which he and other

investigators applied were unavailing. These facts were definitely

made known by Andrews in 1869, were theoretically developed by Van

der Waals in 1873, and practically applied to the liquefaction of

oxygen in 1877, independently and almost simultaneously, by Pictet, of

Geneva, and Cailletet, of Châtillon-sur-Seine. Pictet exposed oxygen,

under great pressure, to the cold produced by the rapid evaporation

of liquid carbon dioxide; Cailletet brought about the same result by

suddenly diminishing the tension of the strongly compressed oxygen, the

rapid expansion of the gas effecting the reduction of its temperature

below the critical point. Other workers took up the subject, notably

Wroblewski and Olszewki in Poland, Dewar in England, and Kammerlingh

Onnes in Holland; and the liquefaction of all the gases has now been

accomplished.

The following table shows the _absolute_ boiling-(B.P.) and

melting-points (M.P.), critical points (C.P.), and pressures

(C.Press.), together with the density (D) at their boiling-points of a

number of liquefied gases:

B. P. M. P. C. P. Press. D.

_degrees_ _degrees_ _degrees_ _m._

Helium 4.5 —— —— —— 0.15

Hydrogen 20 15 35 11.6 0.06

Oxygen 90.5 below 50 154 44 1.131

Nitrogen 77.5 60 124 20.9 0.791

Methane 108.3 —— 191 42.4 0.416

Ethylene 169.5 104 282 44 0.571

Fluorine 186 40 —— —— 1.11

Chlorine 239.6 —— —— —— 1.507

Ammonia 234.5 197.5 404 85.9 ——

Neon 30.40 —— below 65 —— ——

Argon 86.90 —— 155.6 40.2 1.212

Krypton 121.33 —— 210.5 41.2 2.155

Xenon 163.9 —— 287.8 43.5 3.52

The principle of the Cailletet method of effecting the liquefaction of

oxygen had been theoretically and experimentally studied by Joule and

Lord Kelvin many years previously. It was extended by Siemens and has

been applied by Linde and Hampson to the construction of machinery for

the production of liquid air on a large scale, without the use of any

intermediate refrigerant.

It is now readily possible to procure considerable quantities of liquid

air, and even of liquid hydrogen. By the evaporation of liquid hydrogen

temperatures approaching the _absolute zero_—that is, 273° C. below

the melting-point of ice—can now be reached. Incidentally there has

been developed a special field of inquiry relating to the behaviour of

substances at low temperatures.

[Illustration: SIR JAMES DEWAR.]

The pioneers in this field have been Dewar in England and Kammerlingh

Onnes in Holland. Research at low temperatures, indeed, has been

the main feature of the work of the Royal Institution of Great

Britain during the last twenty years. It has included observations

at temperatures approaching the absolute zero, on the electrical

resistivity of metals and alloys, on the behaviour of so-called

insulators, on changes in the cohesive force of metals, on the

dielectric constants of frozen electrolytes, on the influence of cold

on magnetisation and on magnetic permeability, and on the optical

behaviour of bodies, on vital phenomena at low temperatures, and on the

influence of cold on chemical change.

Dewar has succeeded in liquefying and solidifying large quantities

of hydrogen, and has studied its properties at low temperatures.

Liquid hydrogen is transparent and colourless. It is a non-conductor

of electricity, and gives no absorption spectrum. It freezes into an

ice-like solid, devoid of metallic properties. Dewar has made use of

the property possessed by charcoal of occluding gases, especially

at low temperatures, in the production of high vacua, and in the

separation of gases; and he has also determined the molecular heat

of absorption by charcoal of various gases. He has employed liquid

air, liquid nitrogen, and liquid hydrogen as calorimetric agents, and

has determined by means of them the heat capacities of a number of

substances at very low temperatures. Lastly, his ingenious contrivance

of silvered vacuum protected vessels, now introduced into commerce

under the name of “Thermos flasks,” has greatly facilitated the

manipulation of liquefied gases for experimental purposes.

CHAPTER VI

THE PERIODIC LAW

In an anonymous essay “On the Relation between the Specific Gravities

of Bodies in their Gaseous State and the Weights of their Atoms,”

published in Thomson’s _Annals of Philosophy_ in 1815, the attempt

was made to indicate certain consequences which seem to follow from

Dalton’s law of gaseous volumes, as generalised by Gay Lussac. The

author of this essay was subsequently discovered to be a medical

student named William Prout, noteworthy as having been one of the

first to point out the suggestiveness of the numerical relationships

which occur among the atomic weights of the elements. This paper is

usually assumed to contain the statement that the atomic weights of the

elements are multiples of that of hydrogen. As a fact, however, this

hypothesis is nowhere explicitly stated in the paper. The inference was

practically due to Thomson, who strove to support it by experimental

proof of so weak a character as to draw forth the remark of Berzelius

that much of it appeared to have been made at the writing-desk.

Nevertheless, the occurrence of such numerical relationships continued,

as already stated, to excite speculation. Döbereiner, in 1829, pointed

out that in certain groups of correlated elements, consisting each

of three members, the middle member had an atomic weight practically

identical with the arithmetic mean of the atomic weights of the others;

and similar observations were made by Gmelin, Dumas, Gladstone, and

Strecker. An approach to the recognition of the general law underlying

these facts was made by Newlands in England, and independently by

De Chancourtois in France, who were the first to indicate that the

properties of the elements are related to their atomic weights. This

conception was developed by the Russian chemist, Mendeléeff. In

Mendeléeff’s arrangement, first published in 1869, the elements are so

grouped that their properties are periodic functions of their atomic

weights. The general statement of what is now known as the Periodic

Law may be put in this form: If the elements are arranged in order

of increasing atomic weight, the properties of these elements vary

from member to member of the series, but return more or less nearly

to the same value at certain fixed points in the series. This is

observed to occur in the atomic value, or valency, of the several

members; also in their specific volumes, melting-points, ductility,

hardness, volatility, crystalline form, thermal expansion, refraction

equivalents, and conductivities for heat and electricity, in their

magnetic properties and electro-chemical behaviour, and in their heats

of chemical combination, etc.

The first chemist of note to grasp the significance of Mendeléeff’s

generalisation was Lothar Meyer, who, dealing at the outset with one of

the characteristic properties of the elements—viz., their specific or

atomic volumes (that is, the values obtained by dividing their specific

gravities into their respective atomic weights)—greatly developed

the principle of periodicity, representing it graphically in a most

striking and suggestive manner, leading up to a classification almost

identical with that of Mendeléeff.

Since the date of its promulgation the scheme of classification

of the elements in accordance with the principle of periodicity

has experienced certain minor modifications necessitated by fuller

knowledge; but in its essential features it remains very much in the

form devised by Mendeléeff. The discovery of the so-called inert and

radio-active elements required that their relations to the periodic law

should be defined. Their inclusion raises no fundamental difficulty.

Indeed, the generalisation seems to adapt itself to the far-reaching

considerations which spring from modern views of the nature of the

atom, its electro-chemical relationships, and the orderly arrangement

of the corpuscles of which it may be composed. In the 1905 edition

of the English translation of his famous _Principles of Chemistry_,

Mendeléeff has given a table which may be said to embody his final

views concerning the systematic classification of the elements. This

is reproduced on p. 105. In this table he postulates the existence of

two hypothetical elements, _x_ and _y_, the former of which he regards

as identical with the physical ether; while the latter is an analogue

of helium, possibly identical with the “coronium” of the solar coronal

atmosphere, with a molecular weight of about 0.4.

The striking feature of Mendeléeff’s generalisation is its

universality. In this respect it differs from all previous attempts

at natural classifications of the elements; these were limited and

partial, and therefore unsatisfactory. Nevertheless, it is easy to

trace in them fundamental conceptions upon which Mendeléeff built.

Mendeléeff, in fact, gave a great extension to ideas with which the

chemical world of half a century ago was more or less familiar; and

doubtless it was this circumstance, combined with the remarkable

boldness and comprehensiveness of this extension, followed almost

immediately by a most striking series of confirmations of his own

previsions, as logical consequences of his generalisation, that

secured for it attention, and ultimately universal adoption.

-------+------------+------------+------------+------------+-

-------+------------+------------+------------+------------+-

0 | _x_ | —— | —— | —— |

| | | | |

1 | _y_ | Hydrogen. | | |

| | H = 1.008 | —— | —— |

| | | | |

| He = 4.0 | Li = 7.03 | Be = 9.1 | B = 11.0 |

| | | | |

| Ne = 19.9 | Na = 23.05 | Mg = 24.1 | Al = 27.0 |

| | | | |

| Ar = 38 | K = 39.1 | Ca = 40.1 | Sc = 44.1 |

| | | | |

| | Cu = 63.6 | Zn = 65.4 | Ga = 70.0 |

| | | | |

| Kr=81.8 | Rb = 85.4 | Sr = 87.6 | Y = 89.0 |

| | | | |

| | Ag = 107.9 | Cd = 112.4 | In = 114.0 |

| | | | |

| Xe = 128 | Cs = 132.2 | Ba = 137.4 | La = 139 |

| | | | |

9 | —— | —— | —— | —— |

| | | | |

10 | —— | —— | —— | Ytterbium. |

| | | | Yb = 173 |

| | | | |

| | Au = 197.2 | Hg = 200.0 | Tl = 204.1 |

| | | | |

12 | —— | —— | Radium. | —— |

| | | Rd = 224 | |

-------+------------+------------+------------+------------+-

-------+------------+------------+------------+------------+-

0 | —— | —— | —— | —— |

| | | | |

1 | | | | |

| —— | —— | —— | —— |

| | | | |

| C = 12.0 | N = 14.04 | O = 16.0 | F = 19.0 |

| | | | |

| Si = 28.4 | P = 31.0 | S = 32.06 | Cl = 35.45 |

| | | | |

| Ti = 48.1 | V = 51.4 | Cr = 52.1 | Mn = 55.0 |

| | | | |

| Ge = 72.3 | As = 75.0 | Se = 79.0 | Br = 79.95 |

| | | | |

| Zr = 90.6 | Nb = 94.0 | Mo = 96.0 | |

| | | | |

| Sn = 119.0 | Sb = 120.0 | Te = 127 | I = 127 |

| | | | |

8 | Cerium. | —— | —— | —— |

| Ce = 140 | | | |

| | | | |

9 | —— | —— | —— | —— |

| | | | |

10 | —— | Tantalum. | Tungsten. | —— |

| | Ta = 183.0 | W = 184 | |

| | | | |

11 | Lead. | Bismuth. | —— | —— |

| Pb = 206.9 | Bi = 208 | | |

| | | | |

12 | Thorium. | —— | Uranium. | —— |

| Th = 232 | | U = 239 | |

-------+------------+------------+------------+------------+-

-------+----------------

Series.| Group VIII.

-------+----------------

0 | --

1 |

| --

2 | --

3 | --

|{ Iron.

|{ Fe = 55.9

4 |{ Cobalt.

|{ Co = 59

|{ Nickel.

|{ Ni = 59(Cu)

5 | --

|{ Ruthenium.

|{ Ru = 101.7

6 |{ Rhodium.

|{ Rh = 103.0

|{ Palladium.

|{Pd = 106.5(Ag)

7 | --

8 | --

9 | --

|{ Osmium.

|{ Os = 191

10 |{ Iridium.

|{ Ir = 193

|{ Platinum.

|{Pt = 194.9(Au)

11 | --

12 | --

-------+-----------------

The periodic law, in the words of its author, is the “direct outcome

of the stock of generalisations of established facts which had been

accumulated by the end of the decade 1860–1870.” It is founded

wholly on experiment, and is as much the embodiment of fact as are

the laws of chemical combination. It was based upon the adoption of

the definite numerical values of the atomic weights, as indicated

by Cannizzaro, as a consequence of the hypothesis of Avogadro, and

upon the assumption that the relations between the atomic weights of

analogous elements must be governed by a general law. The application

of the periodic law immediately led to the re-determination of certain

atomic weights and to the correction of their assumed atomic values.

At the time of its enunciation the determination of the valency of

an element was purely empirical, with no apparent necessary relation

to that of other elements. We find now that the valency is a matter

of _a priori_ knowledge, just as much as any other property of the

element. The amended values for the atomic weight and valency of a

number of elements thus demanded by the law have been confirmed by all

the experimental criteria employed by chemists. The generalisation

further indicated the existence of new elements; it pointed out their

probable sources, and foretold their properties. Instances of this

power of divination in the law are to be seen, as already mentioned,

in the discovery of _gallium_ by Lecoq de Boisbaudran, of _scandium_

by Nilson, and of _germanium_ by Winkler, the existence and main

properties of which were severally foretold by Mendeléeff in 1871.

The promulgation of the law was heralded as a proof of the validity of

the conception of a primordial matter. It was held that it can find

a rational explanation only in the idea of unity in the formative

material. But its author would not admit that his generalisation had

any relation to the Pythagorean hypothesis:

The periodic law, based as it is on the solid and wholesome ground

of experimental research, has been evolved independently of any

conception as to the nature of the elements. It does not in the

least originate in the idea of an unique matter, and it has no

historical connection with that relic of the torments of classical

thought; and therefore it affords no more indication of the unity

of matter or of the compound nature of the elements than do the

laws of Avogadro, and Gerhardt, or the law of specific heats, or

even the conclusions of spectrum analysis. None of the advocates

of a unique matter has ever tried to explain the law from the

standpoint of ideas taken from a remote antiquity, when it was

found convenient to admit the existence of many gods—and of a

unique matter.

The reader who desires a fuller exposition of the principles of the

periodic law must be referred to special treatises on the subject, or

to the larger manuals on general chemistry. It must, however, be stated

that, while many facts discovered since the original promulgation of

the principle and since its development by Lothar Meyer, Carnelley,

Thomsen, and others, are consistent with the law, other facts, some

of which were known before 1870, are apparently out of harmony with

it, or at all events await a fuller interpretation. For example,

tellurium is not in its proper place in the scheme if its atomic

weight, 127.5, has been correctly ascertained. Cobalt (58.97) and

nickel (58.68) have atomic weights so closely accordant that their

properties and those of their corresponding compounds should be very

similar, and, in fact, almost identical; but such is not the case.

Indeed, it has been said, no prevision of the periodic law would

have led to the discovery of nickel. Similar considerations apply to

manganese, chromium, and iron; the atomic weights of these elements

are less widely different than the differences in their properties and

the divergence in their chemical relationships would seem to require.

The relative positions of argon and potassium are also not consistent

with the law. There are difficulties, too, connected with what we

know at present concerning the atomic weights of the so-called rare

earth metals. In spite, however, of these seeming anomalies, it can

hardly be doubted that the periodic law is as much the expression of

a natural law as is the law of gravitation; although it is possible,

and indeed probable, that, as we now define it, it is only the first

approximation to the truth, and that, as our knowledge becomes more

precise, Mendeléeff’s classification, in its present form, will require

modification and extension, just as Mendeléeff’s own scheme may be said

to be a modification and extension of the attempts at the rational

classification of the chemical elements made by his predecessors.

[Illustration: DMITRI IVANOWITSCH MENDELÉEFF.]

│Dmitri Ivanowitsch Mendeléeff│, with whose name this fruitful

generalisation is indissolubly connected, was born February 7, 1834

(N.S.), at Tobolsk, in Siberia, and was the fourteenth and youngest

child of Ivan Mendeléeff, the Director of the gymnasium at that place.

Soon after the birth of Dmitri his father became blind, and the

family were practically dependent upon the mother, Maria Dmitrievna

Mendeleeva, who established a glass works near Tobolsk, on the profits

of which she brought up and educated her large family. At the age of

fifteen Mendeléeff was taken by his mother to St. Petersburg, and

began the study of natural science at the Physico-Mathematical Faculty

of the Institute. After serving as a science master at Simferopol

in the Crimea and at Odessa, in 1856 he became a _privat-docent_ in

the University; then, following a short period of study in France

and Germany, he returned to St. Petersburg, and in 1866 he was made

Professor of General Chemistry in the University. His reputation mainly

rests upon his contributions to chemical philosophy and physical

chemistry, notably on specific volumes, on critical temperatures, on

the thermal expansion of liquids, on the nature of solutions, on the

elasticity of gases, and the origin and nature of petroleum. He died on

January 31, 1907.

CHAPTER VII

VALENCY

Chemical formulæ, from the time of Berzelius onwards, have been

regarded as rational expressions—that is, they serve to represent

the relations and analogies of the substance they are employed to

designate, and indicate in the simplest and at the same time the most

comprehensive manner the chemical changes in which the substances take

part. In the words of Gerhardt, those formulæ are “the best that make

evident the greatest number of such relations and analogies,” and that

serve to express the greatest number of the chemical changes in which

they are concerned.

In such concrete expressions of chemical change it was frequently

observed that a definite group of some or all of the constituent

elements of the substance hung together, as it were, and passed,

apparently unchanged, into the products of its transformation. These

groups were not necessarily radicals in the sense in which Liebig and

Wöhler used the term; to Gerhardt and to Kekulé they were simply

_residues_, remaining unattacked in a chemical metamorphosis, and

passing as such into the products of the change. They might or might

not be capable of isolation as definite entities. Thus, for example, we

may represent the composition of the following sulphur compounds so as

to show that they all contain the group SO2, or _sulphuryl_:

SO2{Cl SO2{Cl

{Cl {OH

Sulphuryl chloride. Chlorosulphonic acid.

SO2{NO2 SO2{NO2 SO2{OH

{Cl {OH {OH

Sulphuryl nitryl Leaden chamber Sulphuric

chloride. crystals. acid.

These formulæ serve to show how the several substances are mutually

related, and that they may be derived from one another by the

substitution of atoms of chlorine for hydroxyl (OH), or nitryl (NO2),

or _vice versa_.

It was pointed out in 1851 by Williamson, and subsequently by Gerhardt,

that these groups are characterised by differences in their power of

combining with or replacing atoms of hydrogen, or of groups or elements

which, like chlorine, are chemically equivalent to hydrogen. Such a

radical or residue as _ethyl_ (C2H5) is chemically equivalent to _one_

atom of hydrogen, as is shown when we compare the formula for ether, as

established by Williamson, with that of ordinary alcohol:

C2H5}O C2H5}O

H } C2H5}

Alcohol. Ether.

_Sulphuryl_, SO2, is chemically equivalento _two_ atoms of hydrogen;

_phosphoryl_, PO, as suggested by Odling, to _three_ atoms of hydrogen.

Gerhardt therefore proposed to designate these and similar groups as

_monatomic_, _diatomic_, _triatomic_, according to their respective

hydrogen-replacing power.

This conception of the definite atom-fixing or replacing power of

groups or compound radicals was extended by Frankland, in 1852, so as

to include the simple radical—that is, the elements. In the memoir

in which he announced the existence of the organometallic compounds

he pointed out that the elements may be classified according to

their combining power, or, as he expressed it, according as “their

affinities are best satisfied.” This idea was independently developed

by Couper and Kekulé in 1858; it is from that period that the definite

introduction of the conception of _atomicity_, _atomic-value_, or

_valency_, into chemical doctrine may be said to date.

The memoir in Liebig’s _Annalen der Chemie und Pharmacie_, in which

Kekulé announced his views, deals particularly with the tetravalency

of carbon and the doctrine of linking of atoms in terms of their

valency. As formulated by Kekulé and as subsequently developed in his

famous text-book, this doctrine exercised an immediate effect on the

progress of the chemistry of carbon compounds. Like every fruitful

hypothesis, it stimulated inquiry, and brought out analogies; and

the more it was applied the more apparent became its suggestiveness

and utility. The scope of chemical formulæ was greatly extended.

Rational formulæ grew into dissected or constitutional formulæ; and

on the system of constitutional formulæ have been grafted successive

attempts to elucidate the manner in which the constituents of a

molecule are grouped and held together. It is interesting to note

that the proximate effect of the theory of chemical structure which

grew out of Kekulé’s doctrine was to assimilate what was sound in the

seemingly antagonistic theories of types and radicals. As a mode of

exposition, Kekulé used models to illustrate the manner in which the

affinity-values of compounds are satisfied; these were not intended

to represent the actual spatial distribution of the atoms in a

molecule, but they nevertheless familiarised the mind with the idea

first clearly recognised by Wollaston and Berzelius that this is the

ultimate aim of chemistry. It was probably their use, either actually

or by visualisation, that led Kekulé in 1865 to his theory of the

constitution of benzene, as developed in his paper on the constitution

of the aromatic compounds—a theory no less fruitful in its consequences

than that of the tetravalency of carbon and of the linkage of atoms.

Such models, too, in the hands of Van ’t Hoff, subsequently served to

elucidate the connection between optical characters and crystalline

form, and to explain the isomerism of certain organic substances.

Kekulé was of opinion that the valency, or affinity-value, of an

element was a definite and invariable quantity—a fundamental property

of the atom as immutable as its atomic weight. Many facts appear to

show that such is not the case. Thus phosphorus and nitrogen are

sometimes trivalent and at other times pentavalent; tin, in certain

of its compounds, is divalent; in others, tetravalent. Sulphur may

be a dyad, a tetrad, or a hexad. It will be seen that the valency of

these particular elements varies by two units: this was at one time

held to be a natural law, and the various elements were divided by

Frankland into the two main groups of (1) _perissads_, or elements of

odd atomic value, and (2) _artiads_, or elements of even atomic value.

Experience has demonstrated that a rigid classification on this basis

is not possible. Many instances are known of elements not only varying

in valency by two units, but even by one unit. Thus nitrogen, which

is usually a perissad, is apparently an artiad in nitric oxide and in

gaseous nitrogen peroxide. Roscoe has shown that uranium and tungsten,

originally regarded as artiads, form pentachlorides.

To what the difference in the affinity-value of an element is due, and

why different elements should manifest different values, is at present

unknown. Valency, like other properties, appears to be a periodic

function of atomic weight; from the behaviour of such analogous

compounds as phosphorus pentafluoride, phosphorus pentachloride,

phosphorus pentabromide, it seems, too, to be related to the weights

of the atoms in combination. Further, it would appear that the mutual

affinities of substances vary with temperature—_i.e._, with the energy

imparted to their molecules; numerous instances appear to indicate

that the atom-fixing power of an element decreases when it is strongly

heated—that is, when the internal energy imparted to its combinations

exceeds a certain limiting value. Van ’t Hoff has attempted a

mechanical explanation of valency depending on the shape of the atoms,

as affected by variation in their vibratory motions resulting from

differences of temperature. Helmholtz suggested that the different

charges of electricity associated with the atoms may determine their

affinity-values—that, for example, a monad carries a single charge, a

dyad two, a triad three charges. Many considerations go to show that

the affinity-value of an element is not capable of definite numerical

expression in the sense which the doctrine of valency as generally

understood implies, and that the variations are not of the _per saltum_

character assumed by saying that the affinity-value is sometimes 1,

sometimes 2, at other times 3, and so on. When we have apparently

satisfied the accepted atomic value of an element by allocating to it

what we regard as the necessary complement of atoms of other bodies, it

is frequently evident that the capacity for combination of the whole

molecule is not satisfied. Many apparently saturated molecules have

the power of combining with other equally saturated molecules. Sulphur

trioxide (SO3) and barium monoxide (BaO) would appear each to have

their affinity-values satisfied; nevertheless they combine with great

readiness to form barium sulphate, BaSO4.

CHAPTER VIII

THE CHEMISTRY OF AROMATIC COMPOUNDS

The suggestions of Couper and Kekulé that an explanation of the

properties of chemical compounds should be sought in the nature and

mutual affinities of their constituent elements rather than of their

radicals were not wholly accepted at the time they were first made.

Speculative ideas have to justify themselves by facts. The value of

an hypothesis depends upon its usefulness and expediency, and on

its power of indicating the lines of future inquiry. How far it is

inductively sound and deductively useful is a matter for individual

judgment. Consequently the tendency to pass from purely rational and

constitutional formulæ to formulæ which sought to symbolise the inner

structure—the very skeleton, as it were—of a molecule, was resisted for

a time, and by no one more strongly than by Kolbe.

Kolbe’s attitude to the new doctrine may be said to have had its

justification in his own work. His remarkable prediction, based on

considerations which had nothing in common with Kekulé’s doctrine, of

the existence of the secondary and tertiary alcohols, so soon to be

confirmed by Friedel’s discovery of secondary propyl alcohol, and by

Butlerow’s isolation of tertiary butyl alcohol, served to retard the

general adoption of Kekulé’s views by showing that apparently they

were no more fruitful in suggestiveness than those they were intended

to supplant. But it was exactly in their suggestiveness with regard to

the development of isomerism that structural formulæ based upon valency

were gradually found to be most useful. It was perceived that it was

now possible not only to foretell the existence of isomers, but to

determine their number, and to some extent to forecast their properties

and modes of decomposition. Cayley, for example, calculated the number

of possible isomers of the hydrocarbons of the generic formula CnH2n+2

up to C6H14 all those that theory predicted have been discovered. In

no single case have more been obtained than the number indicated by

theory. The accumulated weight of this and similar testimony ultimately

established the doctrine of chemical structure on a firm basis.

This conception received a great extension as the result of Kekulé’s

application of his ideas to the explanation of the chemical

constitution of the group of substances of vegetable origin—consisting

of essential oils, balsams, resins, and their products, which, on

account of their characteristic odours, were collectively known to

the older chemists as the _aromatic compounds_. Some of these, like

oil of bitter almonds, gum benzoin, coumarin, oil of wintergreen, oil

of anise, oil of cinnamon, oil of cumin, balsam of tolu, phenol, and

certain of their derivatives, such as benzene, aniline, salicylic acid,

cinnamic acid, toluene, cymene, had already been investigated with

important theoretical results; but as a class they had received far

less attention than the derivatives of the great group of homologous

radicals of which methyl is the initial member. Of course it was part

of the doctrine of Liebig—the discoverer of benzoyl—that the aromatic

compounds also contained specific radicals; but the relation of these

compounds to those we now call aliphatic (fatty) compounds was not

understood, although certain analogies were recognised.

In 1866 Kekulé drew attention to the following significant

peculiarities of the aromatic compounds: (1) All aromatic compounds,

even the simplest, are comparatively richer in carbon than the

corresponding class of fatty (aliphatic) compounds; (2) among the

aromatic substances, as among fatty compounds, numerous homologous

compounds exist; (3) the simplest aromatic substances contain at

least six atoms of carbon; (4) all decomposition products of aromatic

substances show a certain family resemblance; the main product of the

decomposition contains at least six atoms of carbon—_e.g._, benzene

C6H6, phenol C6H6O, etc., which would seem to indicate that all

aromatic substances contain a nucleus or atomic grouping containing

six carbon atoms. Within this nucleus the carbon atoms are in closer

connection or denser combination, from which it follows that all

aromatic compounds are comparatively rich in carbon. More carbon atoms

can then be added to this nucleus according to the same laws that

govern the fatty compounds. In this way the existence of homologous

compounds may be explained.

On the assumption that carbon is tetravalent and that its valency is

constant, Kekulé showed how, by linking together six carbon atoms by

alternate single and double bonds, six affinity units may be left

free. If we assume that six carbon atoms are attached to one another

according to this law of symmetry, we obtain a group which, regarded as

an _open chain_, contains _eight_ unsaturated units of affinity:

——C══C——C══C——C══C——

| | | | | |

By making the further assumption that the two carbon atoms at the

ends of the chain are linked together by one unit of affinity each,

a _closed chain_ (a symmetrical ring) is obtained which now contains

_six_ unsaturated units of affinity:

+--------------+

| |

C══C——C══C——C══C

| | | | | |

From this _closed chain_ all the substances usually designated as

“aromatic compounds” are derived. In these a common nucleus may be

assumed: it is the closed chain C6A6, where A denotes an unsaturated

affinity. The six affinities of this nucleus may be satisfied by six

monovalent elements. They may also, wholly or in part, be satisfied by

one affinity of polyvalent elements, the latter necessarily bringing

with them other atoms into the compound, thus producing one or more

side chains, which in their turn may be lengthened by the addition of

other atoms.

If each of the free units is satisfied by an atom of hydrogen, we

obtain benzene, which, as Kekulé demonstrated, becomes the centre round

which the great group of aromatic compounds might be said to revolve.

Benzene was discovered by Faraday in 1825 among the volatile liquids

condensed from the oil-gas made by the Portable Gas Company. It had

already played a notable part in the development of chemical theory

in connection with the discovery of isomerism. It was now to play a

far more important rôle: to become, in fact, the progenitor of a great

family of substances, not only of theoretical value, but of great

economic importance.

The limits of this work preclude any attempt to trace in detail the

development of the conception with which Kekulé enriched science, or to

dilate upon the great extension of benzenoid or cyclic chemistry which

has resulted from it during the past forty years. It has been said

that Kekulé’s memoir on the benzene theory is the most brilliant piece

of scientific prediction to be found in the whole range of organic

chemistry. Of course, on its promulgation it had to run the gauntlet

of criticism; and an army of eager, active workers was soon engaged in

testing its sufficiency and in developing the rich province which it

first made known. As the facts multiplied, other statical formulæ were

suggested by Dewar, Ladenburg, and Claus, but they have not proved more

adequate to explain the facts as these have become better understood.

Observations which seemed to contradict Kekulé’s theory, or which

seemed to be imperfectly explained by it, have, in the light of fuller

knowledge, been shown to be in harmony with it; and such additional

proofs of agreement have thereby served to strengthen its position.

Its capacity for development is, indeed, as in the case of every

other hypothesis of the first rank, one of its cardinal qualities. It

adequately explains the constitution of great numbers of derivatives

whose analogies and relations, apart from it, would have remained

obscure and in many cases unintelligible. The symmetrical distribution

of the carbon and hydrogen atoms in the benzene molecule, assumed by

Kekulé on indirect grounds, has been established by the independent

investigations of Ladenburg and others, and its ring structure has been

demonstrated by Baeyer and Perkin. Purely physical evidence, based

upon its thermo-chemical and optical characters can be adduced in its

support. Determinations of the molecular volume and magnetic rotation

of its compounds further serve to substantiate it.

[Illustration: AUGUST KEKULÉ VON STRADONITZ.]

│Friedrich August Kekulé│ was born at Darmstadt on September 7, 1829.

After passing through the gymnasium of his native town, he entered,

in 1847, the University of Giessen, with the intention of becoming an

architect. Attracted by Liebig’s teaching, he turned to chemistry,

and worked with Will on _amyl sulphuric acid_ and its salts. In 1851

he went to Paris, heard Dumas’s lectures, and formed a friendship

with Gerhardt, whose _Traité de Chimie Organique_ largely moulded his

views. He became an assistant to Von Planta, occupying himself with

the chemistry of the alkaloids. Subsequently he came to London,

worked under Stenhouse, and made the acquaintance of Williamson, then

in the full vigour of his scientific activity. Here he discovered

_thioacetic acid_. It was at this time, also, that his ideas with

regard to structural chemistry began to take shape. Returning to

Germany, he attached himself to the University of Heidelberg as a

_privat-docent_, and had for a pupil Baeyer, who took up the study of

the organo-arsenic compounds. In 1858 he published his memorable paper

“On the Constitution and Metamorphoses of Chemical Compounds and on

the Chemical Nature of Carbon,” in which he developed his views on the

linking of atoms, out of which has grown our system of constitutional

formulæ. The immediate result of this celebrated memoir was a call

to the chemical chair of the University of Ghent, where Kekulé had

among other students Baeyer, Hübner, Körner, Ladenburg, Linnemann, and

Dewar. Here he remained nine years, and here he published his classical

_Lehrbuch der Organischen Chemie_. The years he spent in Ghent were the

most productive time of his career, and it was there that he developed

his benzene theory—a conception as fruitful as that of his doctrine

of atom-linking. In 1867 Kekulé was called to Bonn to take charge of

the newly erected laboratory which Hofmann had designed. Although he

continued to work, mostly in collaboration with his pupils, among whom

may be named Anschütz, Bernthsen, Thorpe, Carnelley, Claisen, Dittmar,

Franchimont, Van ’t Hoff, Japp, Schultz, Wallach, and Zincke, his

health after 1876 began to fail. He died on July 13, 1896.

* * * * *

Of course no statical formula can be the ultimate representation of

the constitution of benzene. However convenient and suggestive such a

formula may be, it can be only a transitional phase in its complete

chemical and physical history. Kekulé was early conscious of this

fact, and suggested a dynamical hypothesis based upon a mechanical

conception of valency. This he imagined might represent the number

of contacts with other atoms which a vibrating atom experienced in

the unit of time. Two atoms of tetravalent carbon, each linked by

one combining unit, will experience four oscillations, striking each

other and three other atoms in the unit of time, while the monovalent

hydrogen atom makes only one oscillation. The doubly linked carbon will

collide with its neighbouring atom twice, and also with two other atoms

within the same period. The assumption that the carbon atom has a more

rapid motion than the hydrogen atom is, however, not warranted by the

kinetic theory. Other dynamic formulæ have been proposed by Knorr and

by Collie. Collie and Baly have further suggested that the absorption

bands of benzene observed in the ultra violet of its spectrum point to

synchronous oscillations of its molecule, due to dynamic changes in

the making and breaking of the links between the several pairs of the

carbon atoms, setting up vibrations in the benzene ring comparable with

those of an elastic ring in the act of expanding and contracting.

* * * * *

The large group of the _essential oils_, containing hydrocarbons

similar to oil of turpentine, and classed under the generic term

of _terpenes_, might, from their origin and mode of occurrence, be

expected to be allied in constitution to the aromatic compounds; and

such is found to be the case. The terpenes are isomeric hydrocarbons

of the formula C10H16. They are found sometimes singly, at other times

mixed, in a great variety of plants, associated with _sesquiterpenes_

C15H24, and oxygenated substances, such as camphor, borneol, menthol,

etc., some of which have long been known and valued for their medicinal

properties and technical applications. The elucidation of their

constitution has taxed the skill of many workers during the past

thirty years; but, thanks to the labours of Wallach, Baeyer, Perkin,

Tiemann, Bredt, Komppa, and others, an insight has been gained into

their nature and analogies. They are apparently all cyclic compounds

with certain attributes which connect them with hydrocarbons of the

aliphatic series. _Pinene_, the characteristic constituent of oil

of turpentine, obtained by distilling the resinous exudations of

many species of pines, exists in two modifications, distinguished by

differences in optical activity, known respectively as _australene_,

found in American, Russian, and Swedish turpentine, and _terebenthene_,

found mainly in French turpentine. It would seem from their empirical

formulæ, as well as from their association in nature, that the terpenes

and _camphor_, which Dumas first showed to have the composition

C10H16O, should be closely allied in constitution, and that it ought

to be readily possible to effect their mutual transformation. The

constitution of camphor was long one of the standing problems of

organic chemistry, and dozens of formulæ have been suggested at

various times during the last twenty years in explanation of its

structure. That it contained a benzene nucleus seemed to be proved

by the ease with which it yielded toluene, cymene, and other benzene

homologues. The first real insight into its structure was gained

when Bredt ascertained the constitution of _camphoronic acid_, C6H11

(CO2H)4—a product, together with _camphoric acid_, of the oxidation

of camphor—which he found broke up into trimethylsuccinic acid and

_iso_butyric acid, and the structure of which was established by Perkin

and J. F. Thorpe.

The result of the Japanese monopoly has been to greatly enhance the

price of natural camphor; during the last ten years it has practically

trebled. This has naturally stimulated endeavours to prepare this

substance by synthetical means. _Artificial camphor_ is now made from

_pinene_ by transforming the hydrocarbon into bornyl chloride by the

action of hydrochloric acid. From this _camphene_ is prepared; by

treatment with glacial acetic acid it forms _isobornyl acetate_. On

hydrolysis this is transformed into _isoborneol_, which by oxidation

yields _camphor_, differing from the naturally occurring variety only

in the fact that it is optically inactive. All so-called aromatic

compounds are not necessarily cyclic systems, for it has been

recognised within the past few years that some of the most valuable

natural perfumes, such as that of the rose, lavender, and orange

blossom, lemon-grass, geranium, ylang-ylang, neroli, etc., owe their

characteristic aroma to the presence of terpenes and camphors, which

are not strictly benzenoid or cyclic compounds, but “ruptured rings”

behaving like open-chain or aliphatic substances. To judge from past

experience, it may confidently be stated that, now the constitution

of these substances is understood, their synthetical preparation on

an industrial scale is practicable. The discovery by Cahours in 1844

that _oil of wintergreen_ is substantially methyl salicylate led to

its artificial production from synthetically prepared salicylic acid.

Sir William Perkin in 1868 effected the synthesis of _coumarin_, the

aromatic principle in woodruff and hay. Fittig and Mielck in 1869

synthesised _heliotropin_, and in 1871 Tiemann and Haarmann obtained

_vanillin_, the characteristic aromatic body in the vanilla pod, by

synthetic means, and established its manufacture on a commercial scale.

The chemical nature of the characteristic odoriferous substances in oil

of cumin, anise, rue, cinnamon, heliotrope, jasmine, violet, parsley,

etc., has now been established and some of them are made industrially.

The artificial essence of violets known as _ionone_, prepared by

Tiemann in 1893, and now made commercially, is similar but not

identical in structure with the true perfume—_irone_. What is known as

_artificial musk_ is a trinitro-butyl toluol. _Artificial orange-flower

oil_ is a methyl ester of anthranilic acid.

In Vol. I. a short account has been given of the early history of

the large and important group of vegetable products known as the

_alkaloids_. Many of these have long been valued on account of their

powerful physiological action. As they all contain nitrogen and are

generally basic, they were regarded by Berzelius, and subsequently

by Liebig and Hofmann, as akin to ammonia in constitution, and were

classed as amines. The first experimental evidence of their nature

was obtained by Gerhardt, who found that, when strychnine and certain

of the alkaloids belonging to the quinine group are treated with

potash, an oil was obtained which he termed _quinoline_, and which was

recognised by Hofmann as identical with a substance obtained in 1834

from coal-tar by Runge, and at that time known as _leucol_. By other

modes of treatment certain alkaloids—_e.g._, nicotine and conine—are

found to yield pyridine, a basic substance found by Anderson, in 1846,

in the fœtid liquor obtained by distilling bones, and since found in

coal-tar. Others of them—_e.g._, papaverine, narcotine, etc.—yield

_isoquinoline_, an oil also discovered in coal-tar, by Hoogewerff, and

Van Dorp, in 1885. These three substances—quinoline, _iso_quinoline,

and pyridine—constitute so many nuclei in the constitution of a large

number of alkaloids. Pyridine resembles benzene in being a cyclic

compound, consisting of five carbon atoms and one nitrogen atom.

Quinoline stands to pyridine in much the same relation that naphthalene

stands to benzene. It can be obtained synthetically, as first shown by

Koenigs and Skraup, and subsequently by Doebner and Von Miller, from

benzene derivatives.

_Iso_quinoline, isomeric with quinoline, differs from that substance

in the position of the nitrogen atom. It, too, has been synthetically

prepared from benzene derivatives in a number of ways.

Among the naturally occurring pyridine alkaloids may be named

_piperine_, found in black pepper, and _conine_, the poisonous

principle of hemlock (_conium maculatum_). The latter alkaloid was

prepared synthetically by Ladenburg in 1886; as first obtained

it differed from the naturally occurring product, which is

dextro-rotatory, in being optically inactive. Ladenburg surmised that

the synthetic preparation stood to the naturally occurring compound

in the same relation that racemic acid stood to tartaric acid, and

that, by treatment in the manner employed by Pasteur, the racemic

modification of conine might be separated into its dextro- and

lævo-constituents. This was found to be the case; but the separated

dextro component was now found to be distinctly more optically

active than the pure, natural variety. It was, in fact, an isomeric

modification—_iso_-conine. By heating this to 300° it was transformed

into ordinary conine, identical in all respects with the natural

alkaloid. Ladenburg has also effected the synthesis of piperine by

condensing piperidine and piperinic acid.

_Nicotine_, the alkaloid of tobacco, was discovered by Posselt and

Reimann in 1828. Its constitution was first ascertained by Pinner, and

it was synthetically obtained by Amé Pictet, in 1904, as an inactive

substance, capable of being resolved by the crystallisation of its

tartrates into a dextro- and lævo-modification, the latter of which was

identical with that found in the tobacco leaf.

_Atropine_ and _hyoscyamine_—the poisonous principles of belladonna

and henbane—are isomeric alkaloids, the former of which is optically

inactive, and the latter is lævo-rotatory. Atropine is, in fact, the

racemic modification. The constitution of both alkaloids is known, and

their synthesis is now possible.

The successive steps may be thus indicated:

1. _Synthesis of glycerin_ (Faraday, Kolbe, Melsens, Boerhave, Friedel,

and Silva).

2. _Glycerin to glutaric acid_ (Berthelot and De Luca, Cahours and

Hofmann, Erlenmeyer, Lermantoff, and Markownikoff).

3. _Glutaric acid to suberone_ (Brown and Walker, Boussingault).

4. _Suberone to tropidine_ (Willstätter).

5. _Tropidine to tropine_ (Willstätter, Ladenburg).

6. _Synthesis of tropic acid_ (Berthelot, Fittig and Tollens, Friedel,

Ladenburg, and Rügheimer).

7. _Tropine and tropic acid: atropine_ (Ladenburg).

The alkaloid _cocaïne_, contained in the leaves of _erythroxylon

coca_ and now employed as a local anæsthetic, was discovered by

Niemann in 1860. It has been shown to be closely related to atropine

in constitution, and has now been synthetically prepared in the

dextro-modification.

The alkaloids _papaverine_, _narcotine_, _narceïne_, contained in

opium, are derivatives of _iso_quinoline, as also is _berberine_, found

in the common barberry (_berberis vulgaris_). Papaverine, which occurs

in opium to the extent of about one per cent., was first isolated by

Merck in 1848. Its constitution has been established by Goldschmidt.

_Narcotine_ is, next to morphine, the most abundant constituent of

opium. The study of the products of its hydrolysis and oxidation—viz.,

_opianic acid_ and _cotarnine_, both of which substances have long

been known—has indicated its probable structure. _Narceïne_ is closely

allied to narcotine, and can, indeed, be obtained from it by combining

the latter alkaloid with methyl iodide and treating the compound with

caustic potash. The constitution of _berberine_, which is one of the

few coloured vegeto-alkaloids known, has been worked out by Perkin. As

yet nothing definite is known concerning the structure of the most

important and largest constituent of opium—viz., _morphine_; or of its

congeners _codeïne_ and _thebaine_. Grimaux, however, in 1881 converted

morphine into codeïne by treatment with methyl iodide and potash; hence

the two alkaloids stand in a relation somewhat similar to that in which

narceïne stands to narcotine. There is very little doubt that the

three alkaloids are very closely related, and that a knowledge of the

constitution of one of them would immediately elucidate the structure

of the others. They are probably phenanthrene derivatives.

_Quinine_ and _cinchonine_, the most important of the cinchona

alkaloids, are quinoline compounds, and are closely related in

constitution. But the many attempts to unravel their structure have

yielded no definite results up to the present.

CHAPTER IX

STEREO-ISOMERISM: STEREO-CHEMISTRY

The first gropings in the search for light on the inner structure

of molecular groupings may be said to date from Biot’s work

on polarisation. In 1815 Biot, a pupil of Malus, made the

remarkable discovery that a number of naturally occurring organic

compounds—_e.g._, sugar, tartaric acid, oil of turpentine, camphor,

etc., are _optically active_—that is, rotate the plane of polarisation

in one direction or the other. The property had previously been

observed in quartz, and was assumed to be connected with the

crystalline character of that substance. Biot, however, pointed out

that the case of oil of turpentine which is a liquid, and the cases

of the other substances when in solution, showed that crystalline

character had no necessary connection with the phenomenon, but that it

must be dependent upon the internal or molecular arrangement of the

optically active substance.

In 1844 Mitscherlich, who first demonstrated the relation between

atomic constitution and crystalline form, drew attention to the

fact that the salts of the isomeric modifications of tartaric

acid, studied by Berzelius, although possessing the same chemical

composition, the same crystalline form, with the same angles, the

same double refraction, and therefore the same angles between their

optical axes, nevertheless behave quite differently as regards their

optical activity, solutions of the tartrates rotating the plane of

polarisation, whereas those of the racemates are inactive. In 1848

this remarkable circumstance engaged the attention of Louis Pasteur,

a young man who had just completed his course at the École Normale in

Paris, and was acting as assistant to Balard, the discoverer of the

element bromine. Pasteur, on examining the crystals of the two forms

of tartaric acid, and of some of their salts, detected the presence,

on some of them, of certain facets—so-called hemihedral faces—which

had hitherto been unrecognised, but were similar to facets which Haüy

had observed on quartz. Haüy had, in fact, divided quartz crystals

into two classes—right-handed and left-handed, depending upon the

side on which these facets occurred. The forms were, as it is termed,

enantiomorphous. Biot, moreover, found that some quartz crystals, cut

parallel to the axis, turned the plane of polarisation to the right,

whereas others turned it to the left; and Herschel suggested that the

phenomena were probably connected, and such was found to be the case.

Mindful of Herschel’s observation, Pasteur found that the crystals of

certain of the optically active tartrates showed hemihedral faces,

whereas those of the corresponding racemates showed no trace of them.

On recrystallising the racemates, however, it was noticed that two sets

of crystals were formed—enantiomorphic forms—the first set of crystals

having hemihedral forms on the right-hand side, and the second set

on the left-hand side. The forms, in fact, were so related that one

appeared, as if it were the image, as seen in a mirror, of the other.

When solutions of these crystals were examined, one set was found to

rotate to the right, the other to an equal degree to the left. The

dextro-rotatory salt yielded ordinary tartaric acid; the corresponding

lævo-rotatory acid was a hitherto unknown modification: the two

together, in equal proportions, constituted racemic acid.

In 1863 Wislicenus published a remarkable memoir on the synthesis of

lactic acid. The acid in sour milk was discovered by Scheele in 1780.

In 1807 Berzelius discovered a similar acid, called _sarcolactic acid_,

in muscle juice; this was erroneously pronounced by Liebig to be

identical with that of sour milk. Other forms of lactic acid were made

known, the structural character of which was not to be explained by

current hypotheses. Wislicenus concluded that their differences could

be due only to different arrangements of their atoms in space.

In 1874 the conception of atomic grouping received a remarkable

development by the publication of two memoirs—one by Van ’t Hoff, and

the other by Le Bel—which served to connect molecular structure with

optical activity. Confining their attention to carbon compounds, they

inferred that all optically active substances contained at least one

multivalent atom, united to other atoms or groups, so as to form in

space an unsymmetrical arrangement. Van ’t Hoff regarded the carbon

atom as occupying the centre of a tetrahedron, to the summits of which

its valencies were directed. If different groupings are attached to

these summits, the structure is _asymmetrical_, and is optically

active. The two forms of lactic acid, for example, may be represented

by the following space formulæ:

[Illustration]

It will be seen from an inspection of the figures that the one is the

image-form of the other, and, no matter how they are turned, they are

not superposable; they are right- and left-handed, or, as it is termed,

enantiomorphs.

There is no fundamental distinction between the hypothesis of Van ’t

Hoff and Le Bel as to the effect of asymmetry on optical behaviour. Le

Bel regards the effect of asymmetry simply as a necessary consequence

of the presence of four dissimilar groupings, and as independent of

valency and the geometrical form of the molecule.

[Illustration: JACOBUS HENRICUS VAN ’T HOFF.]

It was surmised by Pasteur that every liquid or solid in solution

showing optical activity, if crystallisable, would be found to manifest

hemihedral faces; but this has not been generally established.

Further, it does not always happen that an optically active substance

in solution is so when solid. Lastly, optical activity may be latent

even in asymmetric carbon compounds if dextro- or lævo-modifications

are present in equal proportions, as in racemic acid. Such compounds

are, in fact, termed “racemic,” or _racemoids_; and they may be

separated occasionally by crystallisation, as in Pasteur’s method with

the tartrates; or as shown by him by the action of the racemoid upon

another optically active substance; or, lastly, by taking advantage

of the specific action (specific assimilation) of organisms—Pasteur’s

so-called biochemical method.

It is a physiological fact of great interest that the behaviour of

enantiomorphs towards the animal organism is frequently markedly

different. Lævo-tartaric acid administered to guinea-pigs is found to

be twice as poisonous as the dextro-acid; dextro-asparagine possesses

a sweet taste, but lævo-asparagine is tasteless; lævo-nicotine is more

poisonous than the dextro-alkaloid.

The ferments known as _enzymes_ are also found to possess the power

of selection, behaving differently towards the different optically

active modifications of the same substance. It is frequently observed

that an optically active substance may be rendered inactive by the

conversion of half the substance into its enantiomorph. This operation

was first performed by Pasteur, and may be brought about by heating

the substance, either alone or with water, under pressure. Indeed, it

is occasionally observed to take place at the ordinary temperature

(_autoracemisation_).

By the action of various reagents the derivatives of an optically

active substance are found not unfrequently to change the direction of

their optical activity. Indeed, by such means one enantiomorph may be

changed into another. Thus _lævo_-menthol may be converted into the

_dextro_-modification by treatment with sulphuric acid.

The rotatory power of a substance is frequently modified by the

character of its solvent, and varies with the temperature and

concentration of the solution. Landolt and Oudemans found that the

specific rotation of dilute solutions of tartrates and of salts of the

active alkaloids was independent of the nature of the base and acid

respectively present—a fact which finds its explanation in the theory

of electrolytic dissociation. It has been known for some years past

that the specific rotation of solutions of certain sugars changes with

time, being sometimes less and sometimes more than the initial amount.

This phenomenon is now known as _multirotation_, or _mutarotation_. It

seems to be connected with an alteration in the configuration of the

molecules.

There is a special case of stereo-isomerism, differing from that

of optical isomerism and of structural isomerism (with which we

have hitherto been alone concerned), which was predicted by Van ’t

Hoff in his remarkable work _La Chimie dans l’Espace_, published in

1877—noteworthy as being the first serious attempt to grapple with

the problem of spatial molecular grouping, foreshadowed by Wollaston,

Berzelius, and, indeed, all the early philosophic thinkers who accepted

the atomic theory. The special form of stereo-isomerism now referred

to, which has been more particularly investigated by Wislicenus, is

distinguished as _geometrical isomerism_; not, perhaps, a sufficiently

descriptive term, since, comprehensively, all forms of isomerism are

really cases of geometrical isomerism. Instances of it are to be

met with among the isomeric acids existing as glycerides in certain

fats, in cinnamic acid, in stilbene and its derivatives, etc. It was

first observed in _maleic_ and _fumaric acids_—isomeric acids of the

empirical formula C2H2 (COOH)2, obtained by the distillation of malic

acid, the characteristic acid met with in the apple and other fruits

and in certain other vegetal products. These acids may be represented

by the following space formulæ:

COOH——C——H COOH——C——H

║ ║

COOH——C——H H——C——COOH

Maleic acid. Fumaric acid.

which show no asymmetry, and hence no possibility of optical activity

or enantiomorphous modifications.

In the case of maleic acid it will be seen that the same groups (COOH

or H) are represented on the same side of the molecule—in other words,

they are placed symmetrically in a plane—whereas in fumaric acid they

are placed diagonally or are axially symmetrical. Isomers of the first

case are classified as _malenoid_ or _cis_-forms, while those of the

latter are termed _fumaroid_ or _trans_-forms.

Substances of the character referred to are, as a rule, mutually

convertible with more or less ease; they are susceptible of what is

called _geometrical inversion_. Thus fumaric acid may be readily

converted into maleic acid by heating; maleic chloride is gradually

transformed into fumaric chloride at ordinary temperatures. Sunlight,

or a particular solvent, or the presence of some substance which acts

as a catalyst, may effect the inversion. _Cis_ and _trans_ isomerism is

also met with among cyclic compounds; it occurs among the terpenes; and

certain alkaloids, as, for example, cocaïne, exhibit it.

Although the doctrine of stereo-chemistry was first enunciated in

the case of carbon, and was, indeed, for a time solely confined to

compounds in which carbon was the nucleal element, there is no _a

priori_ reason why the phenomenon should be so restricted. Van ’t

Hoff, in fact, in 1878, discussed the question in relation to nitrogen

compounds. Stereo-isomeric nitrogen derivatives were first obtained

by Victor Meyer and his pupils, and the stereo-chemistry of nitrogen

has since proved to be a very fruitful field of investigation, notably

in the hands of Goldschmidt, Beckmann, Hantzsch and Werner, Le Bel,

Ladenburg, Bamberger, Kipping, H. O. Jones, Pope, and others. The

stereo-chemistry of nitrogen differs from that of carbon, inasmuch as

variation of valency plays a far more important part in the case of

nitrogen than it has hitherto been observed to do in that of carbon;

the spatial representation of the trivalent nitrogen atom differs from

that of the pentavalent atom. Le Bel, in 1891, succeeded in obtaining

an optically active nitrogen enantiomorph by the application of

Pasteur’s biochemical method. Optically active compounds have since

been prepared by Pope and Peachey and H. O. Jones. Pope and Peachey

have also prepared optically active compounds of sulphur, selenium, and

tin; and Kipping has obtained an asymmetric compound of silicon.

In 1863 Geuther, and, independently, Frankland and Duppa, made known

the existence of _aceto-acetic ester_. By Geuther this compound was

termed _ethyl-di-acetic acid_—

CH3.C(OH): CHCOOC2H5

by Frankland and Duppa it was considered to be _acetone-carboxylic

acid_—

CH3.CO.CH2.COOC2H5.

The essential difference in these formulæ, as the two names

respectively indicate, is that the first implies that the ester has an

acidic or hydroxylic character, proved by its forming characteristic

salts; the other that it contains the group CO, proved by its yielding

acetone and the usual reactions of the ketones. The attempt to settle

the constitution of this substance gave rise to much controversy,

and, as it was found to be very reactive, led to a great amount

of conflicting experimental work. The ultimate result was to show

that both formulæ are correct: at the time of reaction the ester

is sometimes hydroxylic, at other times ketonic, or, adopting the

terminology of Brühl, it sometimes shows the _enol_ form, at other

times the _keto_ form. Other substances were subsequently found to

behave in the same way. In 1885 the question was discussed by Laar,

who suggested the term _tautomerism_ (ταὐτό, the same; μέρος, a

part) to denote the fact that one and the same substance could have

structural formulæ varying with conditions of reaction and depending

upon the migrations of certain of its atoms within the molecule. During

the last twenty years a large number of examples of the kind have

been discovered. They are found to occur, not only among aliphatic

substances, but in cyclic and heterocyclic compounds. We now know that

such intermolecular changes may occur by the migration of any of the

elements or groups present in the molecule. Thus, to confine ourselves

to simple and well-known examples, the transformation of sodium phenyl

carbonate into sodium salicylate, discovered by Kolbe, is due to the

wandering of an atom of hydrogen from the benzene residue to oxygen,

thus:

C6H5.O.COONa→C6H4

COONa.

The conversion of the nitriles into the cyanides by heating is due to

the transference of the alkyl radical from the nitrogen atom to the

carbon—

R.NC→NC.R.

Alkyl groups may also be transferred from oxygen to nitrogen; a radical

may detach itself from a carbon atom and wander to a nitrogen atom;

radicals in cyclic compounds may be transferred from the side chains to

the nucleus, etc.

The phenomenon, in fact, is now so general that grave doubts have

been thrown upon the uniform value of deducing the structural formula

of a substance from the study of its decomposition products, or from

the nature of its derivatives, owing to the readiness with which

tautomerism may occur. The change may be brought about by variation of

temperature, by the reagent itself, by the action of a solvent or the

presence of a catalyst—that is, of a substance which _apparently_ plays

no part in the metamorphosis. Hence the value of specific reagents as

clues to constitution is considerably weakened, since the results may

be equivocal. Fortunately, the great extension, within recent years,

of the application of physical methods has considerably strengthened

our means of gaining an insight into molecular structure; and the

investigations of Brühl on refraction and dispersion, of Perkin on

magnetic rotation, of Hantzsch on electrical conductivity, of Lowry on

solubility, of Lowry and E. F. Armstrong on optical activity, of Knorr

and Findlay on melting-points, and, lastly, of Hartley, Dobbie, Lauder,

Baly, and Desch on absorption spectra, have collectively afforded

valuable information on the mechanism of isomeric change based upon

dynamical considerations.

Space will not permit of a more extended treatment of the subject of

stereo-chemistry; and certain matters relating to it, as, for example,

the phenomena classed under the term _steric hindrance_, must be left

unnoticed. This term has reference to the hindrance which certain

groups, or the particular distribution in space of certain atoms, exert

on the progress or extent of a reaction, as, for example, of hydrolysis

or esterification, etc. The influence of special groupings in retarding

chemical change is apparently well established, but no comprehensive

theory of the subject is yet possible. Until such a theory is

forthcoming a dynamical theory of stereo-chemistry is incomplete.

CHAPTER X

ORGANIC SYNTHESIS: CONDENSATION: THE SYNTHESIS OF VITAL PRODUCTS

In its widest sense, the term “synthesis,” as used in organic

chemistry, means the building-up of carbon compounds, either from

their constituent elements or from groups of differently constituted

molecules. At one period this term was confined to cases in which

the organic compound was prepared from inorganic materials, or from

combinations which themselves could be formed from their elements; but

latterly it has lost, in large measure, this restricted signification.

At the same time, the attempt has been made to indicate by special

terms certain classes of synthetical reactions. Thus the special

case of the formation of an organic compound by the union of two or,

it may be, more molecular groupings is now frequently spoken of as

_condensation_.

Organic chemistry has been largely developed by the discovery from time

to time of special reagents and special types of reactions which have

shown themselves to be capable of extensive application. Such, for

example, was Frankland’s discovery, in 1852, of zinc-ethyl—the first of

the organo-metallic compounds, and the type of a series of substances

of great theoretical importance, and of great practical value by reason

of their reactive powers. They led to the synthesis of the paraffins,

the secondary and tertiary alcohols, and ketones. A few years later

Wurtz introduced the use of metallic sodium as a condensing agent, and

showed thereby how the hydrocarbon _butane_ could be produced from

ethyl iodide:

2C2H5I + Na2 = C4H10 + 2NaI.

Use was made of the same agent by Fittig, in 1863, in effecting the

synthesis of the homologues of benzene by the action of an alkyl iodide

upon bromobenzene:

C6H5Br + CH3I + Na2 = C6H5.CH3 + NaI + NaBr.

In like manner Kekulé, in 1866, obtained benzoic acid by the action of

carbon dioxide upon bromobenzene:

C6H5Br + CO2 + Na2 = C6H5COONa + NaBr.

The readiness with which magnesium can now be obtained, mainly as the

result of Sonstadt’s efforts to develop its metallurgy, has led to its

application, at the suggestion of Barbier, in 1899, in place of zinc.

The particular form of magnesium compound now employed as a reagent was

prepared by Grignard in 1900, and is known by his name. It is obtained

by bringing an ethereal solution of an alkyl iodide or bromide into

contact with magnesium, when the metal is dissolved, forming, in the

case of methyl iodide,

MgCH3I.(C2H5)2O.

Grignard’s reagent has shown itself to be extraordinarily reactive, and

a great number of condensations—of hydrocarbons, alcohols, aldehydes,

acids, ketones, amides, and additive compounds—have been effected by

means of it.

Other condensing reagents of value are aceto-acetic ester, sodium

amalgam, sodamide, sodium ethoxide, dimethyl sulphate, zinc chloride,

aluminium chloride, fused caustic potash, hydrogen chloride,

phenyl-hydrazine, hydrogen peroxide in presence of a ferrous salt

(Fenton’s reagent), ammonia, and various amines. The application of

these reagents has led to the discovery of a variety of new compounds,

the mode of origin of which has served to elucidate their constitution.

The great majority of organic syntheses, especially when they start

by the use of inorganic materials, consist in passing from simple to

complex molecular groupings by condensation processes. An interesting

example of the reverse process is seen in the production of _carbon

suboxide_, or _carbon carbonyl_, C3O2, obtained from various malonyl

compounds, but most conveniently prepared by the action of phosphoric

oxide on malonic acid under diminished pressure, or by treating an

ethereal solution of dibromomalonyl chloride with zinc:

COOH CO

/ //

(1) CH2 = 2H2O + C

\ \\

COOH CO

(2) CBr2(COCl.)2 + Zn2 = ZnCl2 + ZnBr2 C

Carbon suboxide is a colourless, extremely mobile, refractive,

poisonous liquid, of sp. gr. 1.11, with a strong and peculiar

smell. It boils at 7°, and freezes at -107°. It is stable only at

low temperatures; at ordinary temperatures it polymerises to a red

solid, which dissolves in water, forming a solution of the colour of

eosin. The change is almost instantaneous at 100°. Carbon suboxide is

inflammable, burning with a blue but smoky flame: C3O2 + 2O2 = 3CO2.

Its low boiling-point and the high value of its molecular refraction

and dispersion, its general resemblance to the metallic carbonyls and

ketones, etc., indicate that this remarkable oxide of carbon is, in

all probability, the anhydride of malonic acid. Indeed, by the action

of water upon it, it is reconverted into malonic acid.

In point of principle, and viewed as chemical operations, the synthesis

of vital products is in nowise different from the synthesis of any

other group of organic compounds; and the special interest, and even

astonishment, at one time created by the artificial preparation of such

products has largely died away. The synthetical production of some of

the substances formerly known only to be formed by vital action, either

in the animal or the plant, has already been incidentally referred

to. But it may be convenient to treat the subject of the artificial

production of this group of bodies rather more comprehensively and as a

sub-section of this chapter on organic synthesis, since their formation

by such means constitutes a phase in the development of chemistry, and

has undoubtedly exercised a profound influence on scientific thought

and on philosophical and even theological doctrine. During the past

fifty or sixty years the chemist has been enabled to form the active

principles or characteristic products of many plants and animals.

He has built up substances which were formerly regarded as capable

of being made only by the very process of living. He has prepared

compounds which were at one time considered as only producible by

changes in organised matter after death.

Since the date of Wöhler’s epoch-making discovery, already referred

to[4] _urea_ has been synthetically prepared by many reactions,

notably by Regnault and Natanson by the action of ammonia on carbonyl

chloride, and by Basarow and Dexter from ammonium carbamate. Both these

substances can be formed directly or indirectly from their elements. It

may also be obtained by the hydrolysis of lead cyanate:

Pb(CNO)2 + 2H2O = PbCO3 + CO(NH2)2.

[4] Vol. I., p. 163.

The successive steps in its production from inorganic materials by this

method are:

K + C + N → KCN → KCNO

→ Pb(CNO)2 → CO(NH2)2.

Associated with urea as products of metabolism are _uric acid_,

_xanthine_, and _sarcine_. Urea was first artificially transformed into

uric acid by Horbaczewski, and its synthesis was effected by Behrend

and Roosen. Closely related in chemical composition to these substances

are _theobromine_ and _caffeine_, the characteristic principles

respectively of cocoa (the fruit of _theobroma cacao_); and of coffee,

tea, maté (the leaves of _ilex paraguayensis_); “guarana,” obtained

from the seeds of the South American plant _paullinia sorbilis_,

and the kola-nut of Central Africa. Strecker, in 1860, showed how

theobromine may be converted into caffeine; and Emil Fischer, by

similar means, transformed xanthine into theobromine. Since that time

xanthine itself has been prepared artificially. Caffeine can now be

built up from its elements by a series of transformations effected by a

succession of chemists, as follows:

1. Carbon and oxygen give carbonic oxide.—_Priestley_, _Cruickshank_.

2. Carbonic oxide and chlorine give carbonyl chloride.—_J. Davy._

3. Carbonyl chloride and ammonia give urea.—_Natanson._

4. Urea gives uric acid.—_Horbaczewski_; _Behrend and Roosen_.

5. Uric acid gives xanthine.—_E. Fischer._

6. Xanthine gives theobromine.—_Strecker._

7. Theobromine gives caffeine.—_E. Fischer._

Synthetic theobromine is now made on the large scale, and introduced as

a soda compound, in combination with sodium acetate, into medicine as a

diuretic under the name of agurin. Synthetic caffeine is also prepared

on a manufacturing scale from uric acid through the medium of the

methylxanthines. The close relationship of xanthine to uric acid is of

great physiological significance, since there is little doubt that the

xanthine bases are the most important sources of uric acid within the

organism.

In this connection reference may be made to the large number of

synthetic organic products which have been introduced into medicine

during the past few years. The investigation of the constitution of

the alkaloids has served to show in many cases to what particular

molecular grouping the physiological action of the drug is mainly due,

and this has led to the production of substances containing these

groups, but not necessarily existing as natural products. Among these

may be mentioned _antipyrin_, a derivative of the pyrazol group,

discovered by Knorr in 1883, and of which upwards of 17,000 kilos, of

the approximate value of £35,000, were produced in 1899. This substance

is a _phenyl-dimethyl-pyrazolone_.

_Acetanilide_ C6H5NH.COCH3, an aniline derivative, was discovered by

Gerhardt in 1853. _Phenacetin_ is a derivative of _para_-aminophenol:

OC2H5

C6H4

NH.COCH3.

An extraordinary number of synthetical soporifics have been introduced

at various times during recent years—_e.g._, _chloral hydrate_,

_veronal_, _sulphonal_, _trional_ and _tetronal_, etc. The three

last-named substances are closely related, as the following formulæ

indicate:

CH3 CH3

\ \

C(SO2C2H5)2 C(SO2C2H5)2

/ /

CH3 C2H5

Sulphonal. Trional.