Chapter IV: Organic Chemistry

While inorganic chemistry was primarily developed through the study of minerals--a connexion still shown by the French appellation _chimie minerale_--organic chemistry owes its origin to the investigation of substances occurring in the vegetable and animal organisms. The quest of the alchemists for the philosopher's stone, and the almost general adherence of the iatrochemists to the study of the medicinal characters and preparation of metallic compounds, stultified in some measure the investigation of vegetable and animal products. It is true that by the distillation of many herbs, resins and similar substances, several organic compounds had been prepared, and in a few cases employed as medicines; but the prevailing classification of substances by physical and superficial properties led to the correlation of organic and inorganic compounds, without any attention being paid to their chemical composition. The clarification and spirit of research so clearly emphasized by Robert Boyle in the middle of the 17th century is reflected in the classification of substances expounded by Nicolas Lemery, in 1675, in his _Cours de chymie_. Taking as a basis the nature of the source of compounds, he framed three classes: "mineral," comprising the metals, minerals, earths and stones; "vegetable," comprising plants, resins, gums, juices, &c.; and "animal," comprising animals, their different parts and excreta. Notwithstanding the inconsistency of his allocation of substances to the different groups (for instance, acetic acid was placed in the vegetable class, while the acetates and the products of their dry distillation, acetone, &c., were placed in the mineral class), this classification came into favour. The phlogistonists endeavoured to introduce chemical notions to support it: Becher, in his _Physica subterranea_(1669), stated that mineral, vegetable and animal matter contained the same elements, but that more simple combinations prevailed in the mineral kingdom; while Stahl, in his _Specimen Becherianum_ (1702), held the "earthy" principle to predominate in the mineral class, and the "aqueous" and "combustible" in the vegetable and animal classes. It thus happened that in the earlier treatises on phlogistic chemistry organic substances were grouped with all combustibles.

The development of organic chemistry from this time until almost the end of the 18th century was almost entirely confined to such compounds as had practical applications, especially in pharmacy and dyeing. A new and energetic spirit was introduced by Scheele; among other discoveries this gifted experimenter isolated and characterized many organic acids, and proved the general occurrence of glycerin (_Olsuss_) in all oils and fats. Bergman worked in the same direction; while Rouelle was attracted to the study of animal chemistry. Theoretical speculations were revived by Lavoisier, who, having explained the nature of combustion and determined methods for analysing compounds, concluded that vegetable substances ordinarily contained carbon, hydrogen and oxygen, while animal substances generally contained, in addition to these elements, nitrogen, and sometimes phosphorus and sulphur. Lavoisier, to whom chemistry was primarily the chemistry of oxygen compounds, having developed the radical theory initiated by Guyton de Morveau, formulated the hypothesis that vegetable and animal substances were oxides of radicals composed of carbon and hydrogen; moreover, since simple radicals (the elements) can form more than one oxide, he attributed the same character to his hydrocarbon radicals: he considered, for instance, sugar to be a neutral oxide and oxalic acid a higher oxide of a certain radical, for, when oxidized by nitric acid, sugar yields oxalic acid. At the same time, however, he adhered to the classification of Lemery; and it was only when identical compounds were obtained from both vegetable and animal sources that this subdivision was discarded, and the classes were assimilated in the division organic chemistry.

At this time there existed a belief, held at a later date by Berzelius, Gmelin and many others, that the formation of organic compounds was conditioned by a so-called _vital force_; and the difficulty of artificially realizing this action explained the supposed impossibility of synthesizing organic compounds. This dogma was shaken by Wohler's synthesis of urea in 1828. But the belief died hard; the synthesis of urea remained isolated for many years; and many explanations were attempted by the vitalists (as, for instance, that urea was halfway between the inorganic and organic kingdoms, or that the carbon, from which it was obtained, retained the essentials of this hypothetical vital force), but only to succumb at a later date to the indubitable fact that the same laws of chemical combination prevail in both the animate and inanimate kingdoms, and that the artificial or laboratory synthesis of any substance, either inorganic or organic, is but a question of time, once its constitution is determined.[10]

The exact delimitation of inorganic and organic chemistry engrossed many minds for many years; and on this point there existed considerable divergence of opinion for several decades. In addition to the vitalistic doctrine of the origin of organic compounds, views based on purely chemical considerations were advanced. The atomic theory, and its correlatives--the laws of constant and multiple proportions--had been shown to possess absolute validity so far as well-characterized inorganic compounds were concerned; but it was open to question whether organic compounds obeyed the same laws. Berzelius, in 1813 and 1814, by improved methods of analysis, established that the Daltonian laws of combination held in both the inorganic and organic kingdoms; and he adopted the view of Lavoisier that organic compounds were oxides of compound radicals, and therefore necessarily contained at least three elements--carbon, hydrogen and oxygen. This view was accepted in 1817 by Leopold Gmelin, who, in his _Handbuch der Chemie_, regarded inorganic compounds as being of binary composition (the simplest being oxides both acid and basic, which by combination form salts also of binary form), and organic compounds as ternary, i.e. composed of three elements; furthermore, he concluded that inorganic compounds could be synthesized, whereas organic compounds could not. A consequence of this empirical division was that marsh gas, ethylene and cyanogen were regarded as inorganic, and at a later date many other hydrocarbons of undoubtedly organic nature had to be included in the same division.

The binary conception of compounds held by Berzelius received apparent support from the observations of Gay Lussac, in 1815, on the vapour densities of alcohol and ether, which pointed to the conclusion that these substances consisted of one molecule of water and one and two of ethylene respectively; and from Pierre Jean Robiquet and Jean Jacques Colin, showing, in 1816, that ethyl chloride (hydrochloric ether) could be regarded as a compound of ethylene and hydrochloric acid.[11] Compound radicals came to be regarded as the immediate constituents of organic compounds; and, at first, a determination of their empirical composition was supposed to be sufficient to characterize them. To this problem there was added another in about the third decade of the 19th century--namely, to determine the manner in which the atoms composing the radical were combined; this supplementary requisite was due to the discovery of the isomerism of silver fulminate and silver cyanate by Justus von Liebig in 1823, and to M. Faraday's discovery of butylene, isomeric with ethylene, in 1825.

The classical investigation of Liebig and Friedrich Wohler on the radical of benzoic acid ("Uber das Radikal der Benzoe-saure," _Ann. Chem._, 1832, 3, p. 249) is to be regarded as a most important contribution to the radical theory, for it was shown that a radical containing the elements carbon, hydrogen and oxygen, which they named benzoyl (the termination _yl_ coming from the Gr. [Greek: yle], matter), formed the basis of benzaldehyde, benzoic acid, benzoyl chloride, benzoyl bromide and benzoyl sulphide, benzamide and benzoic ether. Berzelius immediately appreciated the importance of this discovery, notwithstanding that he was compelled to reject the theory that oxygen could not play any part in a compound radical--a view which he previously considered as axiomatic; and he suggested the names "proin" or "orthrin" (from the Gr. [Greek: proi] and [Greek: orthros], at dawn). However, in 1833, Berzelius reverted to his earlier opinion that oxygenated radicals were incompatible with his electrochemical theory; he regarded benzoyl as an oxide of the radical C14H10, which he named "picramyl" (from [Greek: pikros], bitter, and [Greek: amygdale], almond), the peroxide being anhydrous benzoic acid; and he dismissed the views of Gay Lussac and Dumas that ethylene was the radical of ether, alcohol and ethyl chloride, setting up in their place the idea that ether was a suboxide of ethyl, (C2H5)2O, which was analogous to K2O, while alcohol was an oxide of a radical C2H6; thus annihilating any relation between these two compounds. This view was modified by Liebig, who regarded ether as ethyl oxide, and alcohol as the hydrate of ethyl oxide; here, however, he was in error, for he attributed to alcohol a molecular weight double its true value. Notwithstanding these errors, the value of the "ethyl theory" was perceived; other radicals--formyl, methyl, amyl, acetyl, &c.--were characterized; Dumas, in 1837, admitted the failure of the etherin theory; and, in company with Liebig, he defined organic chemistry as the "chemistry of compound radicals." The knowledge of compound radicals received further increment at the hands of Robert W. Bunsen, the discoverer of the cacodyl compounds.

The radical theory, essentially dualistic in nature in view of its similarity to the electrochemical theory of Berzelius, was destined to succumb to a unitary theory. Instances had already been recorded of cases where a halogen element replaced hydrogen with the production of a closely allied substance: Gay Lussac had prepared cyanogen chloride from hydrocyanic acid; Faraday, hexachlorethane from ethylene dichloride, &c. Here the electro-negative halogens exercised a function similar to electro-positive hydrogen. Dumas gave especial attention to such substitutions, named _metalepsy_ [Greek: metalepsis], exchange); and framed the following empirical laws to explain the reactions:--(1) a body containing hydrogen when substituted by a halogen loses one atom of hydrogen for every atom of halogen introduced; (2) the same holds if oxygen be present, except that when the oxygen is present as water the latter first loses its hydrogen without replacement, and then substitution according to (1) ensues. Dumas went no further that thus epitomizing his observations; and the next development was made in 1836 by Auguste Laurent, who, having amplified and discussed the applicability of Dumas' views, promulgated his _Nucleus Theory_, which assumed the existence of "original nuclei or radicals" (_radicaux_ or _noyaux fondamentaux_) composed of carbon and hydrogen, and "derived nuclei" (_radicaux_ or _noyaux derives_) formed from the original nuclei by the substitution of hydrogen or the addition of other elements, and having properties closely related to the primary nuclei.

Vigorous opposition was made by Liebig and Berzelius, the latter directing his attack against Dumas, whom he erroneously believed to be the author of what was, in his opinion, a pernicious theory. Dumas repudiated the accusation, affirming that he held exactly contrary views to Laurent; but only to admit their correctness in 1839, when, from his own researches and those of Laurent, Malaguti and Regnault, he formulated his _type theory_. According to this theory a "chemical type" embraced compounds containing the same number of equivalents combined in a like manner and exhibiting similar properties; thus acetic and trichloracetic acids, aldehyde and chloral, marsh gas and chloroform are pairs of compounds referable to the same type. He also postulated, with Regnault, the existence of "molecular or mechanical types" containing substances which, although having the same number of equivalents, are essentially different in characters. His unitary conceptions may be summarized: every chemical compound forms a complete whole, and cannot therefore consist of two parts; and its chemical character depends primarily upon the arrangement and number of the atoms, and, in a lesser degree, upon their chemical nature. More emphatic opposition to the dualistic theory of Berzelius was hardly possible; this illustrious chemist perceived that the validity of his electrochemical theory was called in question, and therefore he waged vigorous war upon Dumas and his followers. But he fought in a futile cause; to explain the facts put forward by Dumas he had to invent intricate and involved hypotheses, which, it must be said, did not meet with general acceptance; Liebig seceded from him, and invited Wohler to endeavour to correct him. Still, till the last Berzelius remained faithful to his original theory; experiment, which he had hitherto held to be the only sure method of research, he discarded, and in its place he substituted pure speculation, which greatly injured the radical theory. At the same time, however, the conception of radicals could not be entirely displaced, for the researches of Liebig and Wohler, and those made subsequently by Bunsen, demonstrated beyond all doubt the advantages which would accrue from their correct recognition.

A step forward--the fusion of Dumas', type theory and the radical theory--was made by Laurent and Charles Gerhardt. As early as 1842, Gerhardt in his _Precis de chimie organique_ exhibited a marked leaning towards Dumas' theory, and it is without doubt that both Dumas and Laurent exercised considerable influence on his views. Unwilling to discard the strictly unitary views of these chemists, or to adopt the copulae theory of Berzelius, he revived the notion of radicals in a new form. According to Gerhardt, the process of substitution consisted of the union of two _residues_ to form a unitary whole; these residues, previously termed "compound radicals," are atomic complexes which remain over from the interaction of two compounds. Thus, he interpreted the interaction of benzene and nitric acid as C6H6 + HNO3 = C6H5NO2 + H2O, the "residues" of benzene being C6H5 and H, and of nitric acid HO and NO2. Similarly he represented the reactions investigated by Liebig and Wohler on benzoyl compounds as double decompositions.

This rejuvenation of the notion of radicals rapidly gained favour; and the complete fusion of the radical theory with the theory of types was not long delayed. In 1849 C.A. Wurtz discovered the amines or substituted ammonias, previously predicted by Liebig; A.W. von Hofmann continued the investigation, and established their recognition as ammonia in which one or more hydrogen atoms had been replaced by hydrocarbon radicals, thus formulating the "ammonia type." In 1850 A.W. Williamson showed how alcohol and ether were to be regarded as derived from water by substituting one or both hydrogen atoms by the ethyl group; he derived acids and the acid anhydrides from the same type; and from a comparison of many inorganic and the simple organic compounds he concluded that this notion of a "water-type" clarified, in no small measure, the conception of the structure of compounds.

These conclusions were co-ordinated in Gerhardt's "new theory of types." Taking as types hydrogen, hydrochloric acid, water and ammonia, he postulated that all organic compounds were referable to these four forms: the hydrogen type included hydrocarbons, aldehydes and ketones; the hydrochloric acid type, the chlorides, bromides and iodides; the water type, the alcohols, ethers, monobasic acids, acid anhydrides, and the analogous sulphur compounds; and the ammonia type, the amines, acid-amides, and the analogous phosphorus and arsenic compounds. The recognition of the polybasicity of acids, which followed from the researches of Thomas Graham and Liebig, had caused Williamson to suggest that dibasic acids could be referred to a double water type, the acid radical replacing an atom of hydrogen in each water molecule; while his discovery of tribasic formic ether, CH(OC2H5)3, in 1854 suggested a triple water type. These views were extended by William Odling, and adopted by Gerhardt, but with modifications of Williamson's aspects. A further generalization was effected by August Kekule, who rejected the hydrochloric acid type as unnecessary, and introduced the methane type and condensed mixed types. Pointing out that condensed types can only be fused with a radical replacing more than one atom of hydrogen, he laid the foundation of the doctrine of valency, a doctrine of incalculable service to the knowledge of the structure of chemical compounds.

At about the same time Hermann Kolbe attempted a rehabilitation, with certain modifications, of the dualistic conception of Berzelius. He rejected the Berzelian tenet as to the unalterability of radicals, and admitted that they exercised a considerable influence upon the compounds with which they were copulated. By his own investigations and those of Sir Edward Frankland it was proved that the radical methyl existed in acetic acid; and by the electrolysis of sodium acetate, Kolbe concluded that he had isolated this radical; in this, however, he was wrong, for he really obtained ethane, C2H6, and not methyl, CH3. From similar investigations of valerianic acid he was led to conclude that fatty acids were oxygen compounds of the radicals hydrogen, methyl, ethyl, &c., combined with the double carbon equivalent C2. Thus the radical of acetic acid, acetyl,[12] was C2H3.C2. (It will be noticed that Kolbe used the atomic weights H=1, C=6, O=8, S=16, &c.; his formulae, however, were molecular formulae, i.e. the molecular weights were the same as in use to-day.) This connecting link, C2, was regarded as essential, while the methyl, ethyl, &c. was but a sort of appendage; but Kolbe could not clearly conceive the manner of copulation.

The brilliant researches of Frankland on the organo-metallic compounds, and his consequent doctrine of saturation capacity or valency of elements and radicals, relieved Kolbe's views of all obscurity. The doctrine of copulae was discarded, and in 1859 emphasis was given to the view that all organic compounds were derivatives of inorganic by simple substitution processes. He was thus enabled to predict compounds then unknown, e.g. the secondary and tertiary alcohols; and with inestimable perspicacity he proved intimate relations between compounds previously held to be quite distinct. Lactic acid and alanine were shown to be oxy- and amino-propionic acids respectively; glycollic acid and glycocoll, oxy- and amino-acetic acids; salicylic and benzamic acids, oxy- and amino-benzoic acids.

Another consequence of the doctrine of valency was that it permitted the graphic representation of the molecule. The "structure theory" (or the mode of linking of the atoms) of carbon compounds, founded by Butlerow, Kekule and Couper and, at a later date, marvellously enhanced by the doctrine of stereo-isomerism, due to J.H. van't Hoff and Le Bel, occupies such a position in organic chemistry that its value can never be transcended. By its aid the molecule is represented as a collection of atoms connected together by valencies in such a manner that the part played by each atom is represented; isomerism, or the existence of two or more chemically different substances having identical molecular weights, is adequately shown; and, most important of all, once the structure is determined, the synthesis of the compound is but a matter of time.

In this summary the leading factors which have contributed to a correct appreciation of organic compounds have so far been considered historically, but instead of continuing this method it has been thought advisable to present an epitome of present-day conclusions, not chronologically, but as exhibiting the principles and subject-matter of our science.

_Classification of Organic Compounds_.

An apt definition of organic chemistry is that it is "the study of the hydrocarbons and their derivatives." This description, although not absolutely comprehensive, serves as a convenient starting-point for a preliminary classification, since a great number of substances, including the most important, are directly referable to hydrocarbons, being formed by replacing one or more hydrogen atoms by other atoms or groups. Two distinct types of hydrocarbons exist: (1) those consisting of an open chain of carbon atoms--named the "aliphatic series" ([Greek: aleiphar], oil or fat), and (2) those consisting of a closed chain--the "carbocyclic series." The second series can be further divided into two groups: (1) those exhibiting properties closely analogous to the aliphatic series--the polymethylenes (q.v.), and (2) a series exhibiting properties differing in many respects from the aliphatic and polymethylene compounds, and characterized by a peculiar stability which is to be associated with the disposition of certain carbon valencies not saturated by hydrogen--the "aromatic series." There also exists an extensive class of compounds termed the "heterocyclic series"--these compounds are derived from ring systems containing atoms other than carbon; this class is more generally allied to the aromatic series than to the aliphatic.

We now proceed to discuss the types of aliphatic compounds; then, the characteristic groupings having been established, an epitome of their derivatives will be given. Carbocyclic rings will next be treated, benzene and its allies in some detail; and finally the heterocyclic nuclei.

Accepting the doctrine of the tetravalency of carbon (its divalency in such compounds as carbon monoxide, various isocyanides, fulminic acid, &c., and its possible trivalency in M. Gomberg's triphenyl-methyl play no part in what follows), it is readily seen that the simplest hydrocarbon has the formula CH4 named methane, in which the hydrogen atoms are of equal value, and which may be pictured as placed at the vertices of a tetrahedron, the carbon atom occupying the centre. This tetrahedral configuration is based on the existence of only one methylene dichloride, two being necessary if the carbon valencies were directed from the centre of a plane square to its corners, and on the existence of two optical isomers of the formula C._A.B.D.E._, C being a carbon atom and _A.B.D.E._ being different monovalent atoms or radicals (see STEREO-ISOMERISM). The equivalence of the four hydrogen atoms of methane rested on indirect evidence, e.g. the existence of only one acetic acid, methyl chloride, and other monosubstitution derivatives--until the experimental proof by L. Henry (_Zeit. f. Phys. Chem._, 1888, 2, p. 553), who prepared the four nitromethanes, CH3NO2, each atom in methane being successively replaced by the nitro-group.

Henry started with methyl iodide, the formula of which we write in the
form CI_{a}H_{b}H_{c}H_{d}. This readily gave with silver nitrite a
nitromethane in which we may suppose the nitro-group to replace the a
iodine atom, i.e. C(NO2)_{a}H_{b}H_{c}H_{d}. The same methyl iodide
gave with potassium cyanide, acetonitril, which was hydrolysed to
acetic acid; this must be C(COOH)_{a}H_{b}H_{c}H_{d}. Chlorination of
this substance gave a monochloracetic acid; we will assume the
chlorine atom to replace the b hydrogen atom. This acid with silver
nitrite gave nitroacetic acid, which readily gave the second
nitromethane, CH_{a}(NO2)_{b}H_{c}H_d identical with the first
nitromethane. From the nitroacetic acid obtained above, malonic acid
was prepared, and from this a monochlormalonic acid was obtained; we
assume the chlorine atom to replace the c hydrogen atom. This acid
gives with silver nitrite the corresponding nitromalonic acid, which
readily yielded the third nitromethane, CH_{a}H_{b}(NO2)_{c}H_{d},
also identical with the first. The fourth nitromethane was obtained
from the nitromalonic acid previously mentioned by a repetition of the
method by which the third was prepared; this was identical with the
other three.

Let us now consider hydrocarbons containing 2 atoms of carbon. Three such compounds are possible according to the number of valencies acting directly between the carbon atoms. Thus, if they are connected by one valency, and the remaining valencies saturated by hydrogen, we obtain the compound H3C.CH3, ethane. This compound may be considered as derived from methane, CH4, by replacing a hydrogen atom by the monovalent group CH3, known as _methyl_; hence ethane may be named "methylmethane." If the carbon atoms are connected by two valencies, we obtain a compound H2C:CH2, ethylene; if by three valencies, HC:CH, acetylene. These last two compounds are termed _unsaturated_, whereas ethane is _saturated_. It is obvious that we have derived three combinations of carbon with hydrogen, characterized by containing a single, double, and triple linkage; and from each of these, by the substitution of a methyl group for a hydrogen atom, compounds of the same nature result. Thus ethane gives H3C.CH2.CH3, propane; ethylene gives H2C:CH.CH3, propylene; and acetylene gives HC:C.CH3, allylene. By continuing the introduction of methyl groups we obtain three series of homologous hydro-carbons given, by the general formulae C_{n}H_{2n+2}, C_{n}H_{2n}, and C_{n}H_{2n-2}, each member differing from the preceding one of the same series by CH2. It will be noticed that compounds containing two double linkages will have the same general formula as the acetylene series; such compounds are known as the "diolefines." Hydrocarbons containing any number of double or triple linkages, as well as both double and triple linkages, are possible, and a considerable number of such compounds have been prepared.

A more complete idea of the notion of a compound radical follows from
a consideration of the compound propane. We derived this substance
from ethane by introducing a methyl group; hence it may be termed
"methylethane." Equally well we may derive it from methane by
replacing a hydrogen atom by the monovalent group CH2.CH3, named
ethyl; hence propane may be considered as "ethylmethane." Further,
since methane may be regarded as formed by the conjunction of a methyl
group with a hydrogen atom, it may be named "methyl hydride";
similarly ethane is "ethyl hydride," propane, "propyl hydride," and so
on. The importance of such groups as methyl, ethyl, &c. in attempting
a nomenclature of organic compounds cannot be overestimated; these
compound radicals, frequently termed _alkyl radicals_, serve a similar
purpose to the organic chemist as the elements to the inorganic
chemist.

In methane and ethane the hydrogen atoms are of equal value, and no matter which one may be substituted by another element or group the same compound will result. In propane, on the other hand, the hydrogen atoms attached to the terminal carbon atoms differ from those joined to the medial atom; we may therefore expect to obtain different compounds according to the position of the hydrogen atom substituted. By introducing a methyl group we may obtain CH3.CH2.CH2.CH3, known as "normal" or n-_butane_, substitution occurring at a terminal atom, or CH3.CH(CH3).CH3, isobutane, substitution occurring at the medial atom. From n-butane we may derive, by a similar substitution of methyl groups, the two hydrocarbons: (1) CH3.CH2.CH2.CH2.CH3, and (2) CH3.CH(CH3).CH2.CH3; from isobutane we may also derive two compounds, one identical with (2.), and a new one (3) CH3(CH3)C(CH3)CH3. These three hydrocarbons are _isomeric_, i.e. they possess the same formula, but differ in constitution. We notice that they may be differentiated as follows: (1) is built up solely of methyl and .CH2. (methylene) groups and the molecule consists of a single chain; such hydrocarbons are referred to as being _normal_; (2) has a branch and contains the group :CH (methine) in which the free valencies are attached to carbon atoms; such hydrocarbons are termed _secondary_ or _iso_-; (3) is characterized by a carbon atom linked directly to four other carbon atoms; such hydrocarbons are known as _tertiary_.

Deferring the detailed discussion of cyclic or ringed hydrocarbons, a correlation of the various types or classes of compounds which may be derived from hydrocarbon nuclei will now be given. It will be seen that each type depends upon a specific radical or atom, and the copulation of this character with any hydrocarbon radical (open or cyclic) gives origin to a compound of the same class.

It is convenient first to consider the effect of introducing one, two, or three hydroxyl (OH) groups into the -CH3, >CH2, and ->CH groups, which we have seen to characterize the different types of hydrocarbons. It may be noticed here that cyclic nuclei can only contain the groups >CH2 and ->CH, the first characterizing the polymethylene and reduced heterocyclic compounds, the second true aromatic compounds.

Substituting one hydroxyl group into each of these residues, we obtain
radicals of the type -CH2.OH, >CH.OH, and ->C.OH; these compounds are
known as _alcohols_ (q.v.), and are termed primary, secondary, and
tertiary respectively. Polymethylenes can give only secondary and
tertiary alcohols, benzene only tertiary; these latter compounds are
known as _phenols_. A second hydroxyl group may be introduced into the
residues -CH2.OH and >CH.OH, with the production of radicals of the
form -CH(OH)2 and >C(OH)2. Compounds containing these groupings are,
however, rarely observed (see CHLORAL), and it is generally found that
when compounds of these types are expected, the elements of water are
split off, and the typical groupings are reduced to -CH:O and >C:O.
Compounds containing the group -CH:O are known as _aldehydes_ (q.v.),
while the group >C:O (sometimes termed the carbonyl or keto group)
characterizes the _ketones_ (q.v.). A third hydroxyl group may be
introduced into the -CH:O residue with the formation of the radical
-C(OH):O; this is known as the carboxyl group, and characterizes the
_organic_ acids.

Sulphur analogues of these oxygen compounds are known. Thus the
thio-alcohols or _mercaptans_ (q.v.) contain the group -CH2.SH; and
the elimination of the elements of sulphuretted hydrogen between two
molecules of a thio-alcohol results in the formation of a thio-ether
or sulphide, R2S. Oxidation of thio-ethers results in the formation of
sulphoxides, R2:S:O, and sulphones, R2:SO2; oxidation of mercaptans
yields sulphonic acids, R.SO3H, and of sodium mercaptides sulphinic
acids, R.SO(OH). We may also notice that thio-ethers combine with
alkyl iodides to form sulphine or sulphonium compounds, R3:SI.
Thio-aldehydes, thio-ketones and thio-acids also exist.

We proceed to consider various simple derivatives of the alcohols, which we may here regard as hydroxy hydrocarbons, R.OH, where R is an alkyl radical, either aliphatic or cyclic in nature.

Of these, undoubtedly the simplest are the _ethers_ (q.v.), formed by
the elimination of the elements of water between two molecules of the
same alcohol, "simple ethers," or of different alcohols, "mixed
ethers." These compounds may be regarded as oxides in just the same
way as the alcohols are regarded as hydroxides. In fact, the analogy
between the alkyl groups and metallic elements forms a convenient
basis from which to consider many derivatives. Thus from ethyl alcohol
there can be prepared compounds, termed _esters_ (q.v.), or ethereal
salts, exactly comparable in structure with corresponding salts of,
say, potassium; by the action of the phosphorus haloids, the hydroxyl
group is replaced by a halogen atom with the formation of derivatives
of the type R.Cl(Br,I); nitric acid forms nitrates, R.O.NO2; nitrous
acid, nitrites, R.O.NO; sulphuric acid gives normal sulphates R2SO4,
or acid sulphates, R.SO4H. Organic acids also condense with alcohols
to form similar compounds: the fats, waxes, and essential oils are
naturally occurring substances of this class.

An important class of compounds, termed _amines_ (q.v.), results from
the condensation of alcohols with ammonia, water being eliminated
between the alcoholic hydroxyl group and a hydrogen atom of the
ammonia. Three types of amines are possible and have been prepared:
primary, R.NH2; secondary, R2:NH; and tertiary, R3:N; the oxamines,
R3N:O, are closely related to the tertiary ammonias, which also unite
with a molecule of alkyl iodide to form salts of quaternary ammonium
bases, e.g. R4N.I. It is worthy of note that phosphorus and arsenic
bases analogous to the amines are known (see PHOSPHORUS and ARSENIC).
From the primary amines are derived the diazo compounds (q.v.) and azo
compounds (q.v.); closely related are the hydrazines (q.v.). Secondary
amines yield nitrosamines, R2N.NO, with nitrous acid. By the action of
hydroxylamine or phenylhydrazine on aldehydes or ketones, condensation
occurs between the carbonyl oxygen of the aldehyde or ketone and the
amino group of the hydroxylamine or hydrazine. Thus with hydroxylamine
aldehydes yield aldoximes, R.CH:N.OH, and ketones, ketoximes, R2C:N.OH
(see OXIMES), while phenyl hydrazine gives phenylhydrazones,
R2C:N.NH.C6H5 (see HYDRAZONES). Oxyaldehydes and oxyketones (viz.
compounds containing an oxy in addition to an aldehydic or ketonic
group) undergo both condensation and oxidation when treated with
phenylhydrazine, forming compounds known as osozones; these are of
great importance in characterizing the sugars (q.v.).

The carboxyl group constitutes another convenient starting-point for the orientation of many types of organic compounds. This group may be considered as resulting from the fusion of a carbonyl (:CO) and a hydroxyl (HO.) group; and we may expect to meet with compounds bearing structural resemblances to the derivatives of alcohols and aldehydes (or ketones).

Considering derivatives primarily concerned with transformations of
the hydroxyl group, we may regard our typical acid as a fusion of a
radical R.CO- (named acetyl, propionyl, butyl, &c., generally
according to the name of the hydrocarbon containing the same number of
carbon atoms) and a hydroxyl group. By replacing the hydroxyl group by
a halogen, acid-haloids result; by the elimination of the elements of
water between two molecules, acid-anhydrides, which may be oxidized to
acid-peroxides; by replacing the hydroxyl group by the group .SH,
thio-acids; by replacing it by the amino group, acid-amides (q.v.); by
replacing it by the group -NH.NH2, acid-hydrazides. The structural
relations of these compounds are here shown:

R.CO.OH; R.CO.Cl; (R.CO)2O; R.CO.SH;
acid; acid-chloride; acid-anhydride; thio-acid;

R.CO.NH2; R.CO.NH.NH2.
acid-amide; acid-hydrazide.

It is necessary clearly to distinguish such compounds as the amino-
(or amido-) acids and acid-amides; in the first case the amino group
is substituted in the hydrocarbon residue, in the second it is
substituted in the carboxyl group.

By transformations of the carbonyl group, and at the same time of the hydroxyl group, many interesting types of nitrogen compounds may be correlated.

Thus from the acid-amides, which we have seen to be closely related to
the acids themselves, we obtain, by replacing the carbonyl oxygen by
chlorine, the acidamido-chlorides, R.CCl2.NH2, from which are derived
the imido-chlorides, R.CCl:NH, by loss of one molecule of hydrochloric
acid. By replacing the chlorine in the imido-chloride by an oxyalkyl
group we obtain the imido-ethers, R.C(OR'):NH; and by an amino group,
the amidines, R.C(NH2):NH. The carbonyl oxygen may also be replaced by
the oxime group, :N.OH; thus the acids yield the hydroxamic acids,
R.C(OH):NOH, and the acid-amides the amidoximes, R.C(NH2):NOH. Closely
related to the amidoximes are the nitrolic acids, R.C(NO2):NOH.

_Cyclic Hydrocarbons and Nuclei._

Having passed in rapid review the various types of compounds derived by substituting for hydrogen various atoms or groups of atoms in hydrocarbons (the separate articles on specific compounds should be consulted for more detailed accounts), we now proceed to consider the closed chain compounds. Here we meet with a great diversity of types: oxygen, nitrogen, sulphur and other elements may, in addition to carbon, combine together in a great number of arrangements to form cyclic nuclei, which exhibit characters closely resembling open-chain compounds in so far as they yield substitution derivatives, and behave as compound radicals. In classifying closed chain compounds, the first step consists in dividing them into: (1) _carbocyclic_, in which the ring is composed solely of carbon atoms--these are also known as _homocyclic_ or _isocyclic_ on account of the identity of the members of the ring--and (2) _heterocyclic_, in which different elements go to make up the ring. Two primary divisions of carbocyclic compounds may be conveniently made: (1) those in which the carbon atoms are completely saturated--these are known by the generic term _polymethylenes_, their general formula being (CH2)_n: it will be noticed that they are isomeric with ethylene and its homologues; they differ, however, from this series in not containing a double linkage, but have a ringed structure; and (2) those containing fewer hydrogen atoms than suffice to saturate the carbon valencies--these are known as the _aromatic compounds_ proper, or as _benzene compounds_, from the predominant part which benzene plays in their constitution.

It was long supposed that the simplest ring obtainable contained six atoms of carbon, and the discovery of trimethylene in 1882 by August Freund by the action of sodium on trimethylene bromide, Br(CH2)3Br, came somewhat as a surprise, especially in view of its behaviour with bromine and hydrogen bromide. In comparison with the isomeric propylene, CH3.HC:CH2, it is remarkably inert, being only very slowly attacked by bromine, which readily combines with propylene. But on the other hand, it is readily converted by hydrobromic acid into normal propyl bromide, CH3.CH2.CH2Br. The separation of carbon atoms united by single affinities in this manner at the time the observation was made was altogether without precedent. A similar behaviour has since been noticed in other trimethylene derivatives, but the fact that bromine, which usually acts so much more readily than hydrobromic acid on unsaturated compounds, should be so inert when hydrobromic acid acts readily is one still needing a satisfactory explanation. A great impetus was given to the study of polymethylene derivatives by the important and unexpected observation made by W.H. Perkin, junr., in 1883, that ethylene and trimethylene bromides are capable of acting in such a way on sodium acetoacetic ester as to form tri- and tetra-methylene rings. Perkin has himself contributed largely to our knowledge of such compounds; penta- and hexa-methylene derivatives have also received considerable attention (see POLYMETHYLENES).

A. von Baeyer has sought to explain the variations in stability manifest in the various polymethylene rings by a purely mechanical hypothesis, the "strain" or _Spannungs_ theory (_Ber._, 1885, p. 2277). Assuming the four valencies of the carbon atom to be directed from the centre of a regular tetrahedron towards its four corners, the angle at which they meet is 109 deg. 28'. Baeyer supposes that in the formation of carbon "rings" the valencies become deflected from their positions, and that the tension thus introduced may be deduced from a comparison of this angle with the angles at which the strained valencies would meet. He regards the amount of deflection as a measure of the stability of the "ring." The readiness with which ethylene is acted on in comparison with other types of hydrocarbon, for example, is in harmony, he considers, with the circumstance that the greatest distortion must be involved in its formation, as if deflected into parallelism each valency will be drawn out of its position through 1/2.109 deg. 28'. The values in other cases are calculable from the formula 1/2(1O9 deg. 28' - a), where a is the internal angle of the regular polygon contained by sides equal in number to the number of the carbon atoms composing the ring. These values are:--

Trimethylene. 1/2(109 deg. 28' - 60 deg.) = 24 deg. 44'.
Tetramethylene. 1/2(109 deg. 28' - 90 deg.) = 9 deg. 44'.
Pentamethylene. 1/2(109 deg. 28' - 108 deg.) = 0 deg. 44'.
Hexamethylene. 1/2(109 deg. 28' - 120 deg.) = -5 deg. 16'.

The general behaviour of the several types of hydrocarbons is certainly in accordance with this conception, and it is a remarkable fact that when benzene is reduced with hydriodic acid, it is converted into a mixture of hexamethylene and methylpentamethylene (cf. W. Markownikov, _Ann._, 1898, 302, p. 1); and many other cases of the conversion of six-carbon rings into five-carbon rings have been recorded (see below, _Decompositions of the Benzene Ring_). Similar considerations will apply to rings containing other elements besides carbon. As an illustration it may be pointed out that in the case of the two known types of lactones--the [gamma]-lactones, which contain four carbon atoms and one oxygen atom in the ring, are more readily formed and more stable (less readily hydrolysed) than the [delta]-lactones, which contain one oxygen and five carbon atoms in the ring. That the number of atoms which can be associated in a ring by single affinities is limited there can be no doubt, but there is not yet sufficient evidence to show where the limit must be placed. Baeyer has suggested that his hypothesis may also be applied to explain the instability of acetylene and its derivatives, and the still greater instability of the polyacetylene compounds.

_Benzene._

The ringed structure of benzene, C6H6, was first suggested in 1865 by August Kekule, who represented the molecule by six CH groups placed at the six angles of a regular hexagon, the sides of which denoted the valencies saturated by adjacent carbon atoms, the fourth valencies of each carbon atom being represented as saturated along alternate sides. This formula, notwithstanding many attempts at both disproving and modifying it, has well stood the test of time; the subject has been the basis of constant discussion, many variations have been proposed, but the original conception of Kekule remains quite as convenient as any of the newer forms, especially when considering the syntheses and decompositions of the benzene complex. It will be seen, however, that the absolute disposition of the fourth valency may be ignored in a great many cases, and consequently the complex may be adequately represented as a hexagon. This symbol is in general use; it is assumed that at each corner there is a CH group which, however, is not always written in; if a hydrogen atom be substituted by another group, then this group is attached to the corner previously occupied by the displaced hydrogen. The following diagrams illustrate these statements:--

CH ^ C.OH OH
/ \\ / \ / \\ / \
HC / \\ CH / \ HC / \\ CH / \
|| | | | || | | |
|| | | | || | | |
HC \ // CH \ / HC \ // CH \ /
\ // \ / \ // \ /
CH v CH v

Benzene. Abbreviated. Oxybenzene. Abbreviated.

From the benzene nucleus we can derive other aromatic nuclei,
graphically represented by fusing two or more hexagons along common
sides. By fusing two nuclei we obtain the formula of naphthalene,
C10H10; by fusing three, the hydrocarbons anthracene and phenanthrene,
C14H10; by fusing four, chrysene, C18H12, and possibly pyrene, C16H10;
by fusing five, picene, C22H14. But it must be here understood that
each member of these _condensed nuclei_ need not necessarily be
identical in structure; thus the central nuclei in anthracene and
phenanthrene differ very considerably from the terminal nuclei (see
below, _Condensed Nuclei_). Other hydrocarbon nuclei generally
classed as aromatic in character result from the union of two or more
benzene nuclei joined by one or two valencies with polymethylene or
oxidized polymethylene rings; instances of such nuclei are indene,
hydrindene, fluorene, and fluor-anthene. From these nuclei an immense
number of derivatives may be obtained, for the hydrogen atoms may be
substituted by any of the radicals discussed in the preceding section
on the classification of organic compounds.

Distinctions between aliphatic and aromatic compounds.

We now proceed to consider the properties, syntheses, decompositions and constitution of the benzene complex. It has already been stated that benzene derivatives may be regarded as formed by the replacement of hydrogen atoms by other elements or radicals in exactly the same manner as in the aliphatic series. Important differences, however, are immediately met with when we consider the methods by which derivatives are obtained. For example: nitric acid and sulphuric acid readily react with benzene and its homologues with the production of nitro derivatives and sulphonic acids, while in the aliphatic series these acids exert no substituting action (in the case of the olefines, the latter acid forms an addition product); another distinction is that the benzene complex is more stable towards oxidizing agents. This and other facts connected with the stability of benzenoid compounds are clearly shown when we consider mixed aliphatic-aromatic hydrocarbons, i.e. compounds derived by substituting aliphatic radicals in the benzene nucleus; such a compound is methylbenzene or toluene, C6H5.CH3. This compound is readily oxidized to benzoic acid, C6H5.COOH, the aromatic residue being unattacked; nitric and sulphuric acids produce nitro-toluenes, C6H4.CH3.NO2, and toluene sulphonic acids, C6H4.CH3.SO3H; chlorination may result in the formation of derivatives substituted either in the aromatic nucleus or in the side chain; the former substitution occurs most readily, chlor-toluenes, C6H4.CH3.Cl, being formed, while the latter, which needs an elevation in temperature or other auxiliary, yields benzyl chloride, C6H5.CH2Cl, and benzal chloride, C6H5.CHCl2. In general, the aliphatic residues in such mixed compounds retain the characters of their class, while the aromatic residues retain the properties of benzene.

Further differences become apparent when various typical compounds are compared. The introduction of hydroxyl groups into the benzene nucleus gives rise to compounds generically named _phenols_, which, although resembling the aliphatic alcohols in their origin, differ from these substances in their increased chemical activity and acid nature. The phenols more closely resemble the tertiary alcohols, since the hydroxyl group is linked to a carbon atom which is united to other carbon atoms by its remaining three valencies; hence on oxidation they cannot yield the corresponding aldehydes, ketones or acids (see below, _Decompositions of the Benzene Ring_). The amines also exhibit striking differences: in the aliphatic series these compounds may be directly formed from the alkyl haloids and ammonia, but in the benzene series this reaction is quite impossible unless the haloid atom be weakened by the presence of other substituents, e.g. nitro groups. Moreover, while methylamine, dimethylamine, and trimethylamine increase in basicity corresponding to the introduction of successive methyl groups, phenylamine or aniline, diphenylamine, and triphenylamine are in decreasing order of basicity, the salts of diphenylamine being decomposed by water. Mixed aromatic-aliphatic amines, both secondary and tertiary, are also more strongly basic than the pure aromatic amines, and less basic than the true aliphatic compounds; e.g. aniline, C6H5.NH2, monomethyl aniline, C6H5.NH.CH3, and dimethyl aniline, C6H5.N(CH3)2, are in increasing order of basicity. These observations may be summarized by saying that the benzene nucleus is more negative in character than the aliphatic residues.

_Isomerism of Benzene Derivatives._--Although Kekule founded his famous benzene formula in 1865 on the assumptions that the six hydrogen atoms in benzene are equivalent and that the molecule is symmetrical, i.e. that two pairs of hydrogen atoms are symmetrically situated with reference to any specified hydrogen atom, the absolute demonstration of the validity of these assumptions was first given by A. Ladenburg in 1874 (see _Ber._, 1874, 7, p. 1684; 1875, 8, p. 1666; _Theorie der aromatischen Verbindungen_, 1876). These results may be graphically represented as follows: numbering the hydrogen atoms in cyclical order from 1 to 6, then the first thesis demands that whichever atom is substituted the same compound results, while the second thesis points out that the pairs 2 and 6, and 3 and 5 are symmetrical with respect to 1, or in other words, the di-substitution derivatives 1.2 and 1.6, and also 1.3 and 1.5 are identical. Therefore three di-derivatives are possible, viz. 1.2 or 1.6, named _ortho_- (o), 1.3 or 1.5, named _meta_- (m), and 1.4, named _para_- compounds (p). In the same way it may be shown that three tri-substitution, three tetra-substitution, one penta-substitution, and one hexa-substitution derivative are possible. Of the tri-substitution derivatives, 1.2.3.-compounds are known as "adjacent" or "vicinal" (v), the 1.2.4 as "asymmetrical" (as), the 1.3.5 as "symmetrical" (s); of the tetra-substitution derivatives, 1.2.3.4-compounds are known as "adjacent," 1.2.3.5 as "asymmetrical," and 1.2.4.5 as "symmetrical."

Di-derivatives Tri-derivatives Tetra-derivatives
_____________________ _____________________ _____________________
/ \ / \ / \
X X X X X X X X X
/\ /\ /\ /\ /\ /\ /\ /\ /\
/ \X / \ / \ / \X / \X / \ / \X / \X / \X
| | | | | | | | | | | | | | | | | |
| | | | | | | | | | | | | | | | | |
\ / \ /X \ / \ /X \ / X\ /X \ /X X\ /X X\ /
\/ \/ \/ \/ \/ \/ \/ \/ \/
X X X X
o m p v as s v as s

Here we have assumed the substituent groups to be alike; when they are unlike, a greater number of isomers is possible. Thus in the tri-substitution derivatives six isomers, and no more, are possible when two of the substituents are alike; for instance, six diaminobenzoic acids, C6H3(NH2)2COOH, are known; when all are unlike ten isomers are possible; thus, ten oxytoluic acids, C6H3.CH3.OH.COOH, are known. In the case of tetra-substituted compounds, thirty isomers are possible when all the groups are different.

Equivalence of four hydrogen atoms.

The preceding considerations render it comparatively easy to follow
the reasoning on which the experimental verification of the above
statements is based. The proof is divided into two parts: (1) that
four hydrogen atoms are equal, and (2) that two pairs of hydrogen
atoms are symmetrical with reference to a specified hydrogen atom. In
the first thesis, phenol or oxybenzene, C6H5.OH, in which we will
assume the hydroxyl group to occupy position 1, is converted into
brombenzene, which is then converted into benzoic acid, C6H5.COOH.
From this substance, an oxybenzoic acid (_meta_-), C6H4.OH.COOH, may
be prepared; and the two other known oxybenzoic acids (_ortho_- and
_para_-) may be converted into benzoic acid. These three acids yield
on heating phenol, identical with the substance started with, and
since in the three oxybenzoic acids the hydroxyl groups must occupy
positions other than 1, it follows that _four_ hydrogen atoms are
equal in value.

Symmetry of pairs of hydrogen atoms.

R. Hubner and A. Petermann (_Ann._, 1869, 149, p. 129) provided the
proof of the equivalence of the atoms 2 and 6 with respect to 1. From
meta-brombenzoic acid two nitrobrombenzoic acids are obtained on
direct nitration; elimination of the bromine atom and the reduction of
the nitro to an amino group in these two acids results in the
formation of the same ortho-aminobenzoic acid. Hence the positions
occupied by the nitro groups in the two different nitrobrombenzoic
acids must be symmetrical with respect to the carboxyl group. In 1879,
Hubner (_Ann._, 195, p. 4) proved the equivalence of the second pair,
viz. 3 and 5, by starting out with ortho-aminobenzoic acid, previously
obtained by two different methods. This substance readily yields
ortho-oxybenzoic acid or salicylic acid, which on nitration yields two
mononitro-oxybenzoic acids. By eliminating the hydroxy groups in these
acids the same nitrobenzoic acid is obtained, which yields on
reduction an aminobenzoic acid different from the starting-out acid.
Therefore there must be another pair of hydrogen atoms, other than 2
and 6, which are symmetrical with respect to 1. The symmetry of the
second pair was also established in 1878 by E. Wroblewsky (_Ann._,
192, p. 196).

_Orientation of Substituent Groups._--The determination of the relative positions of the substituents in a benzene derivative constitutes an important factor in the general investigation of such compounds. Confining our attention, for the present, to di-substitution products we see that there are three distinct series of compounds to be considered. Generally if any group be replaced by another group, then the second group enters the nucleus in the position occupied by the displaced group; this means that if we can definitely orientate three di-derivatives of benzene, then any other compound, which can be obtained from or converted into one of our typical derivatives, may be definitely orientated. Intermolecular transformations--migrations of substituent groups from one carbon atom to another--are of fairly common occurrence among oxy compounds at elevated temperatures. Thus potassium ortho-oxybenzoate is converted into the salt of para-oxybenzoic acid at 220 deg.; the three bromphenols, and also the brombenzenesulphonic acids, yield m-dioxybenzene or resorcin when fused with potash. It is necessary, therefore, to avoid reactions involving such intermolecular migrations when determining the orientation of aromatic compounds.

Such a series of typical compounds are the benzene dicarboxylic acids
(phthalic acids), C6H4(COOH)2. C. Graebe (_Ann._, 1869, 149, p. 22)
orientated the ortho-compound or phthalic acid from its formation from
naphthalene on oxidation; the meta-compound or isophthalic acid is
orientated by its production from mesitylene, shown by A. Ladenburg
(_Ann._, 1875, 179, p. 163) to be symmetrical trimethyl benzene;
terephthalic acid, the remaining isomer, must therefore be the
para-compound.

P. Griess (_Ber._, 1872, 5, p. 192; 1874, 7, p. 1223) orientated the
three diaminobenzenes or phenylene diamines by considering their
preparation by the elimination of the carboxyl group in the six
diaminobenzoic acids. The diaminobenzene resulting from two of these
acids is the ortho-compound; from three, the meta-; and from one the
para-; this is explained by the following scheme:--

NH2 NH2 NH2 NH2 NH2 NH2
^ ^ ^ ^ ^ ^
/ \NH2 / \NH2 / \COOH / \ / \ / \COOH
| | | | | | | | | | | |
| | | | | | | | | | | |
\ /COOH \ / \ /NH2 \ /NH2 HOOC \ /NH2 \ /
v v v v v v
COOH COOH NH2
\________ _______/ , \______________ ______________/ ,
v v
NH2 NH2 NH2
^ ^ ^
/ \NH2 / \NH2 / \
| | | | | |
| | | | | |
\ / \ /NH2 \ /
v v v
COOH NH2

W. Korner (_Gazz. Chem. Ital._, 4, p. 305) in 1874 orientated the
three dibrombenzenes in a somewhat similar manner. Starting with the
three isomeric compounds, he found that one gave two tribrombenzenes,
another gave three, while the third gave only one. A scheme such as
the preceding one shows that the first dibrombenzene must be the
ortho-compound, the second the meta-, and the third the
para-derivative. Further research in this direction was made by D.E.
Noetling (_Ber._, 1885, 18, p. 2657), who investigated the nitro-,
amino-, and oxy-xylenes in their relations to the three xylenes or
dimethyl benzenes.

The orientation of higher substitution derivatives is determined by
considering the di- and tri-substitution compounds into which they can
be transformed.

_Substitution of the Benzene Ring._--As a general rule, homologues and mono-derivatives of benzene react more readily with substituting agents than the parent hydrocarbon; for example, phenol is converted into tribromphenol by the action of bromine water, and into the nitrophenols by dilute nitric acid; similar activity characterizes aniline. Not only does the substituent group modify the readiness with which the derivative is attacked, but also the nature of the product. Starting with a mono-derivative, we have seen that a substituent group may enter in either of three positions to form an ortho-, meta-, or para-compound. Experience has shown that such mono-derivatives as nitro compounds, sulphonic acids, carboxylic acids, aldehydes, and ketones yield as a general rule chiefly the meta-compounds, and this is independent of the nature of the second group introduced; on the other hand, benzene haloids, amino-, homologous-, and hydroxy-benzenes yield principally a mixture of the ortho- and para-compounds. These facts are embodied in the "Rule of Crum Brown and J. Gibson" (_Jour. Chem. Soc._ 61, p. 367): If the hydrogen compound of the substituent already in the benzene nucleus can be directly oxidized to the corresponding hydroxyl compound, then meta-derivatives predominate on further substitution, if not, then ortho- and para-derivatives. By further substitution of ortho- and para-di-derivatives, in general the same tri-derivative [1.2.4] is formed (_Ann._, 1878, 192, p. 219); meta-compounds yield [1.3.4] and [1.2.3] tri-derivatives, except in such cases as when both substituent groups are strongly acid, e.g. m-dinitrobenzene, then [1.3.5]-derivatives are obtained.

_Syntheses of the Benzene Ring._--The characteristic distinctions which exist between aliphatic and benzenoid compounds make the transformations of one class into the other especially interesting.

In the first place we may notice a tendency of several aliphatic
compounds, e.g. methane, tetrachlormethane, &c., to yield aromatic
compounds when subjected to a high temperature, the so-called
pyrogenetic reactions (from Greek [Greek: pyr], fire, and [Greek:
gennao], I produce); the predominance of benzenoid, and related
compounds--naphthalene, anthracene, phenanthrene, &c.--in coal-tar is
probably to be associated with similar pyrocondensations.
Long-continued treatment with halogens may, in some cases, result in
the formation of aromatic compounds; thus perchlorbenzene, C6Cl6,
frequently appears as a product of exhaustive chlorination, while
hexyl iodide, C6H13I, yields perchlor- and perbrom-benzene quite
readily.

The trimolecular polymerization of numerous acetylene
compounds--substances containing two trebly linked carbon atoms,
--C:C--, to form derivatives of benzene is of considerable interest.
M.P.E. Berthelot first accomplished the synthesis of benzene in 1870
by leading acetylene, HC:CH, through tubes heated to dull redness; at
higher temperatures the action becomes reversible, the benzene
yielding diphenyl, diphenylbenzene, and acetylene. The condensation of
acetylene to benzene is also possible at ordinary temperatures by
leading the gas over pyrophoric iron, nickel, cobalt, or spongy
platinum (P. Sabatier and J.B. Senderens). The homologues of acetylene
condense more readily; thus allylene, CH:C.CH3, and crotonylene,
CH3.C:C.CH3, yield trimethyl- and hexamethyl-benzene under the
influence of sulphuric acid. Toluene or mono-methylbenzene results
from the pyrocondensation of a mixture of acetylene and allylene.
Substituted acetylenes also exhibit this form of condensation; for
instance, bromacetylene, BrC:CH, is readily converted into
tribrombenzene, while propiolic acid, HC:C.COOH, under the influence
of sunlight, gives benzene tricarboxylic acid.

A larger and more important series of condensations may be grouped
together as resulting from the elimination of the elements of water
between carbonyl (CO) and methylene (CH2) groups. A historic example is
that of the condensation of three molecules of acetone, CH3.CO.CH3, in
the presence of sulphuric acid, to s-trimethylbenzene or mesitylene,
C6H3(CH3)3, first observed in 1837 by R. Kane; methylethyl ketone and
methyl-n-propyl ketone suffer similar condensations to s-triethylbenzene
and s-tri-n-propylbenzene respectively. Somewhat similar condensations
are: of geranial or citral, (CH3)2CH.CH2.CH:CH.C(CH3):CH.CHO, to
p-isopropyl-methylbenzene or cymene; of the condensation product of
methylethylacrolein and acetone, CH3.CH2.CH:C(CH3).CH:CH.CO.CH3, to
[1.3.4]-trimethylbenzene or pseudocumene; and of the condensation
product of two molecules of isovaleryl aldehyde with one of acetone,
C3H7.CH2.CH:C(C3H7).CH:CH.CO.CH3, to (1)-methyl-2-4-di-isopropyl
benzene. An analogous synthesis is that of di-hydro-m-xylene from methyl
heptenone, (CH3)2C:CH.(CH2)2.CO.CH3. Certain a-diketones condense to
form benzenoid quinones, two molecules of the diketone taking part in
the reaction; thus diacetyl, CH3.CO.CO.CH3, yields p-xyloquinone,
C6H2(CH3)2O2 (_Ber._, 1888, 21, p. 1411), and acetylpropionyl,
CH3.CO.CO.C2H5, yields duroquinone, or tetramethylquinone, C6(CH3)4O2.
Oxymethylene compounds, characterized by the grouping >C:CH(OH), also
give benzene derivatives by hydrolytic condensation between three
molecules; thus oxymethylene acetone, or formyl acetone,
CH3.CO.CH:CH(OH), formed by acting on formic ester with acetone in the
presence of sodium ethylate, readily yields [1.3.5]-triacetylbenzene,
C6H3(CO.CH3)3; oxymethylene acetic ester or formyl acetic ester or
[beta]-oxyacrylic ester, (HO)CH:CH.CO2C2H5, formed by condensing acetic
ester with formic ester, and also its dimolecular condensation product,
coumalic acid, readily yields esters of [1.3.5]-benzene tricarboxylic
acid or trimesic acid (see _Ber._, 1887, 20, p. 2930).

In 1890, O. Doebner (_Ber._ 23, p. 2377) investigated the condensation
of pyroracemic acid, CH3.CO.COOH, with various aliphatic aldehydes,
and obtained from two molecules of the acid and one of the aldehyde in
the presence of baryta water alkylic isophthalic acids: with
acetaldehyde [1.3.5]-methylisophthalic acid or uvitic acid,
C6H3.CH3.(COOH)2, was obtained, with propionic aldehyde
[1.3.5]-ethylisophthalic acid, and with butyric aldehyde the
corresponding propylisophthalic acid. We may here mention the
synthesis of oxyuvitic ester (5-methyl-4-oxy-1-3-benzene dicarboxylic
ester) by the condensation of two molecules of sodium acetoacetic
ester with one of chloroform (_Ann._, 1883, 222, p. 249). Of other
syntheses of true benzene derivatives, mention may be made of the
formation of orcinol or [3.5]-dioxytoluene from dehydracetic acid; and
the formation of esters of oxytoluic acid (5-methyl-3-oxy-benzoic
acid), C6H3.CH3.OH.COOH, when acetoneoxalic ester,
CH3.CO.CH2.CO.CO.CO2C2H5, is boiled with baryta (_Ber._, 1889, 22, p.
3271). Of interest also are H.B. Hill and J. Torray's observations on
nitromalonic aldehyde, NO2.CH(CHO)2, formed by acting on mucobromic
acid, probably CHO.CBr:CBr:COOH, with alkaline nitrites; this
substance condenses with acetone to give p-nitrophenol, and forms
[1.3.5]-trinitrobenzene when its sodium salt is decomposed with an
acid.

By passing carbon monoxide over heated potassium J. von Liebig
discovered, in 1834, an interesting aromatic compound, potassium
carbon monoxide or potassium hexaoxybenzene, the nature of which was
satisfactorily cleared up by R. Nietzki and T. Benckiser (_Ber_. 18,
p. 499) in 1885, who showed that it yielded hexaoxybenzene, C6(OH)6,
when acted upon with dilute hydrochloric acid; further investigation
of this compound brought to light a considerable number of highly
interesting derivatives (see QUINONES). Another hexa-substituted
benzene compound capable of direct synthesis is mellitic acid or
benzene carboxylic acid, C6(COOH)6. This substance, first obtained
from the mineral honeystone, aluminium mellitate, by M.H. Klaproth in
1799, is obtained when pure carbon (graphite or charcoal) is oxidized
by alkaline permanganate, or when carbon forms the positive pole in an
electrolytic cell (_Ber._, 1883, 16, p. 1209). The composition of this
substance was determined by A. von Baeyer in 1870, who obtained
benzene on distilling the calcium salt with lime.

Hitherto we have generally restricted ourselves to syntheses which
result in the production of a true benzene ring; but there are many
reactions by which reduced benzene rings are synthesized, and from the
compounds so obtained true benzenoid compounds may be prepared. Of such
syntheses we may notice: the condensation of sodium malonic ester to
phloroglucin tricarboxylic ester, a substance which gives phloroglucin
or trioxybenzene when fused with alkalis, and behaves both as a
triketohexamethylene tricarboxylic ester and as a trioxybenzene
tricarboxylic ester; the condensation of succinic ester, (CH2.CO2C2H5)2,
under the influence of sodium to succinosuccinic ester, a
diketohexamethylene dicarboxylic ester, which readily yields
dioxyterephthalic acid and hydroquinpne (F. Herrmann, _Ann._, 1882, 211,
p. 306; also see below, _Configuration of the Benzene Complex_); the
condensation of acetone dicarboxylic ester with malonic ester to form
triketohexamethylene dicarboxylic ester (E. Rimini, _Gazz. Chem._, 1896,
26, (2), p. 374); the condensation of acetone-di-propionic acid under
the influence of boiling water to a diketohexamethylene propionic acid
(von Pechmann and Sidgwick, _Ber._, 1904, 37, p. 3816). Many diketo
compounds suffer condensation between two molecules to form hydrobenzene
derivatives, thus [alpha,gamma]-di-acetoglutaric ester,
C2H5O2C(CH3.CO)CH.CH2.CH(CO.CH3)CO2C2H5, yields a
methyl-ketohexamethylene, while [gamma]-acetobutyric ester,
CH3CO(CH2)2CO2C2H5, is converted into dihydroresorcinol or
m-diketohexamethylene by sodium ethylate; this last reaction is reversed
by baryta (see _Decompositions of Benzene Ring_). For other syntheses of
hexamethylene derivatives, see POLYMETHYLENES.

_Decompositions of the Benzene Ring._--We have previously alluded to the relative stability of the benzene complex; consequently reactions which lead to its disruption are all the more interesting, and have engaged the attention of many chemists. If we accept Kekule's formula for the benzene nucleus, then we may expect the double linkages to be opened up partially, either by oxidation or reduction, with the formation of di-, tetra-, or hexa-hydro derivatives, or entirely, with the production of open chain compounds. Generally rupture occurs at more than one point; and rarely are the six carbon atoms of the complex regained as an open chain. Certain compounds withstand ring decomposition much more strongly than others; for instance, benzene and its homologues, carboxylic acids, and nitro compounds are much more stable towards oxidizing agents than amino- and oxy-benzenes, aminophenols, quinones, and oxy-carboxylic acids.

Simple oxidation.

Strong oxidation breaks the benzene complex into such compounds as
carbon dioxide, oxalic acid, formic acid, &c.; such decompositions are
of little interest. More important are Kekule's observations that
nitrous acid oxidizes pyrocatechol or [1.2]-dioxybenzene, and
protocatechuic acid or [3.4]-dioxybenzoic acid to dioxytartaric acid,
(C(OH)2.COOH)2 (_Ann._, 1883, 221, p. 230); and O. Doebner's
preparation of mesotartaric acid, the internally compensated tartaric
acid, (CH(OH).COOH)2, by oxidizing phenol with dilute potassium
permanganate (_Ber._, 1891, 24, p. 1753).

Chlorination and oxidation.

For many years it had been known that a mixture of potassium chlorate
and hydrochloric or sulphuric acids possessed strong oxidizing powers.
L. Carius showed that potassium chlorate and sulphuric acid oxidized
benzene to trichlor-phenomalic acid, a substance afterwards
investigated by Kekule and O. Strecker (_Ann._, 1884, 223, p. 170),
and shown to be [beta]-trichloracetoacrylic acid, CCl3.CO.CH:CH.COOH,
which with baryta gave chloroform and maleic acid. Potassium chlorate
and hydrochloric acid oxidize phenol, salicylic acid (o-oxybenzoic
acid), and gallic acid ([2.3.4] trioxybenzoic acid) to
trichlorpyroracemic acid (isotrichlorglyceric acid), CCl3.C(OH)2.CO2H,
a substance also obtained from trichloracetonitrile, CCl3.CO.CN, by
hydrolysis. We may also notice the conversion of picric acid,
([2.4.6]-trinitrophenol) into chloropicrin, CCl3NO2, by bleaching lime
(calcium hypochlorite), and into bromopicrin, CBr3NO2, by bromine
water.

The action of chlorine upon di-and tri-oxybenzenes has been carefully
investigated by Th. Zincke; and his researches have led to the
discovery of many chlorinated oxidation products which admit of
decomposition into cyclic compounds containing fewer carbon atoms than
characterize the benzene ring, and in turn yielding open-chain or
aliphatic compounds. In general, the rupture occurs between a-keto
group (CO) and a keto-chloride group (CCl2), into which two adjacent
carbon atoms of the ring are converted by the oxidizing and
substituting action of chlorine. Decompositions of this nature were
first discovered in the naphthalene series, where it was found that
derivatives of indene (and of hydrindene and indone) and also of
benzene resulted; Zincke then extended his methods to the
disintegration of the oxybenzenes and obtained analogous results,
R-pentene and aliphatic derivatives being formed (R- symbolizing a
ringed nucleus).

When treated with chlorine, pyrocatechol (1.2 or ortho-dioxybenzene)
(1) yields a tetrachlor ortho-quinone, which suffers further
chlorination to hexachlor-o-diketo-R-hexene (2). This substance is
transformed into hexachlor-R-pentene oxycarboxylic acid (3) when
digested with water; and chromic acid oxidizes this substance to
hexachlor-R-pentene (4). The ring of this compound is ruptured by
caustic soda with the formation of perchlorvinyl acrylic acid (5),
which gives on reduction ethidine propionic acid (6), a compound
containing five of the carbon atoms originally in the benzene ring
(see Zincke, _Ber._, 1894, 27, p. 3364) (the carbon atoms are omitted
in some of the formulae).

Cl Cl Cl
^ ^ ^ ^
// \ OH Cl // \ O Cl // \ /OH Cl / \
| || ==> | | ==> | \CO ==> | \CO ==>
| || | | | / \CO2H | /
\\ / OH Cl2 \ / O Cl2 \ / Cl2 \ /
v v v v
Cl2 Cl2 Cl2

(1) (2) (3) (4)

CCl CH2
// \ / \
Cl C CO2H CH CO2H
| ==> ||
Cl C CH
\\ \
CCl2 CH3

(5) (6)

Resorcin (1.3 or meta dioxybenzene) (1) is decomposed in a somewhat
similar manner. Chlorination in glacial acetic acid solution yields
pentachlor-m-diketo-R-hexene (2) and, at a later stage,
heptachlor-m-diketo-R-hexene (3). These compounds are both decomposed
by water, the former giving dichloraceto-trichlor-crotonic acid (4),
which on boiling with water gives dichlormethyl-vinyl-a-diketone (5).
The heptachlor compound when treated with chlorine water gives
trichloraceto-pentachlorbutyric acid (6), which is hydrolysed by
alkalis to chloroform and pentachlorglutaric acid (7), and is
converted by boiling water into tetrachlor-diketo-R-pentene (8). This
latter compound may be chlorinated to perchloracetoacrylic chloride
(9), from which the corresponding acid (10) is obtained by treatment
with water; alkalis hydrolyse the acid to chloroform and dichlormaleic
acid (11).

OH O O
^ ^ ^
/ \\ Cl / \Cl2 Cl2/ \Cl2
|| | ==> || | ==> | |
|| | || | | |
\ // OH H\ / O HCl\ / O
v v v
Cl2 Cl2
(1) / (2) | (3)
/ v
v HO2C.CCl2.CHCl.CCl2.CO.CCl3
HO2C.CCl:CH.CCl2.CO.CHCl2 | (6) |
| (4) v +--------------+
| HO2C.CCl2.CHCl.CCl2.CO2H.CHCl3 |
CO2 + CHHC:CH.CO.CO.CHCl2 (7) |
(5) +---------------------+
v
+-- CO.CCl2 \
ClOC.CCl:CCl.CO.CCl3 <== | CO (8)
| (9) +-- CCl=CCl /
v
HO2C.CCl:CCl.CO.CCl3 ==> HO2C.CCl:CCl.CO2H + CHCl3
(10) (11)

Hydroquinone (1.4 or para-dioxybenzene) (1) gives with chlorine,
first, a tetrachlorquinone (2), and then hexachlor-p-diketo-R-hexene
(3), which alcoholic potash converts into perchloracroylacrylic acid
(4). This substance, and also the preceding compound, is converted by
aqueous caustic soda into dichlormaleic acid, trichlorethylene, and
hydrochloric acid (5) (Th. Zincke and O. Fuchs, _Ann._, 1892, 267, p.
1).

OH O COOH CO2H CO2H
^ ^ ^ ^ /
// \ Cl / \Cl2 ClC// \Cl2 ClC// \CCl2 ClC CCl2
| || ==> || || ==> || || ==> || || ==> || + ||
| || || || || || || || ClC CHCl
\\ / Cl \ /Cl2 ClC\ /CCl ClC\ /CCl \
v v v v CO2H
OH O O CO

(1) (2) (3) (4) (5)

Phloroglucin (1.3.5-trioxybenzene) (1) behaves similarly to resorcin,
hexachlor [1.3.5] triketo-R-hexylene (2) being first formed. This
compound is converted by chlorine water into octachloracetylacetone
(3); by methyl alcohol into the ester of dichlormalonic acid and
tetrachloracetone (4); whilst ammonia gives dichloracetamide (5) (Th.
Zincke and O. Kegel, _Ber._, 1890, 23, p. 1706).

OH O
^ ^ > (3) Cl2C.CO.CCl2.CO.CCl3.CO2
/ \ CL2/ \CL2 /
| | ==> | | /
| | | | ==> (4) Cl2HC.CO.CHCl2.CH3O2C.CCl2.CO2.CH3
HO \ / OH O \ / O \
v v \
CL2 > (5) Cl2C.CONH2

(1) (2)

Reduction in alkaline solution.

When phenol is oxidized in acid solution by chlorine,
tetrachlorquinone is obtained, a compound also obtainable from
hydroquinone. By conducting the chlorination in alkaline solution, A.
Hantzsch (_Ber._, 1889, 22, p. 1238) succeeded in obtaining
derivatives of o-diketo-R-hexene, which yield R-pentene and aliphatic
compounds on decomposition. When thus chlorinated phenol (1) yields
trichlor-o-diketo-R-hexene (2), which may be hydrolysed to an acid
(3), which, in turn, suffers rearrangement to
trichlor-R-pentene-oxycarboxylic acid (4). Bromine water oxidizes this
substance to oxalic acid and tetrabrom-dichloracetone (5).

OH O HOOC /OH
// \ / \ \ Cl2C_____C
// \ Cl2/ \O HCl2C \CO | |\COOH
| || -> | | -> | | -> | |
| || | | | | | |
\\ / H\\ /H2 HC\\ /CH2 HC\\ /CH2
\\ / \\ / \\ / \\ /
Cl CCl CCl

(1) (2) (3) (4)

-> (5) Cl2BrC.CO.CBr3 + HO2C.CO2H

The reduction of o-oxybenzoic acids by sodium in amyl alcohol solution
has been studied by A. Einhorn and J.S. Lumsden (_Ann._, 1895, 286, p.
257). It is probable that tetrahydro acids are first formed, which
suffer rearrangement to orthoketone carboxylic acids. These substances
absorb water and become pimelic acids. Thus salicylic acid yields
n-pimelic acid, HOOC.(CH2)5.COOH, while o-, m-, and p-cresotinic
acids, C6H3(CH3)(OH)(COOH), yield isomeric methylpimelic acids.

Resorcin on reduction gives dihydroresorcin, which G. Merling (_Ann._,
1894, 278, p. 20) showed to be converted into n-glutaric acid,
HOOC.(CH2)3.COOH, when oxidized with potassium permanganate; according
to D. Vorlander (_Ber._, 1895, 28, p. 2348) it is converted into
[gamma]-acetobutyric acid, CH3CO.(CH2)3.COOH, when heated with baryta
to 150-160 deg.

_Configuration of the Benzene Complex._--The development of the "structure theory" in about 1860 brought in its train an appreciation of the chemical structure of the derivatives of benzene. The pioneer in this field was August Kekule, who, in 1865 (_Ann._, 137, p. 129; see also his _Lehrbuch der organischen Chemie_), submitted his well-known formula for benzene, so founding the "benzene theory" and opening up a problem which, notwithstanding the immense amount of labour since bestowed upon it, still remains imperfectly solved. Arguing from the existence of only one mono-substitution derivative, and of three di-derivatives (statements of which the rigorous proof was then wanting), he was led to arrange the six carbon atoms in a ring, attaching a hydrogen atom to each carbon atom; being left with the fourth carbon valencies, he mutually saturated these in pairs, thus obtaining the symbol I (see below). The value of this ringed structure was readily perceived, but objections were raised with respect to Kekule's disposal of the fourth valencies. In 1866 Sir James Dewar proposed an unsymmetrical form (II); while in 1867, A. Claus (_Theoretische Betrachtungen und deren Anwendung zur Systematik der organischen Chemie_) proposed his diagonal formula (III), and two years later, A. Ladenburg (_Ber._, 2, p. 140) devised his prism formula (IV), the six carbon atoms being placed at the six corners of a right equilateral triangular prism, with its plane projections (V, VI).

CH CH CH
// \ / | \ /|\
HC// \CH HC/ | \CH HC/ | \CH
| || || | || |\|/|
| || || | || | * |
| || || | || |/|\|
HC\\ /CH HC\ | /CH HC\ | /CH
\\ / \ | / \|/
CH CH CH

I Kekule II Dewar III Claus

HC+-----+CH CH CH
|\ /| /|\ /|\
| \ / | / | \ HC--/-+-\--CH
| |CH| HC+--+--+CH \/ \|/ \/
HC+--|--+CH HC+--+--+CH /\ /|\ /\
\ | / \ | / HC--\-+-/--CH
\|/ \|/ \|/
CH CH CH