Chapter I: II III IV

Ladenburg's prism admits of one mono-substitution derivative and three
di-derivatives. Furthermore, it is in accordance with certain simple
syntheses of benzene derivatives (e.g. from acetylene and acetone);
but according to Baeyer (_Ber._, 1886, 19, p. 1797) it fails to
explain the formation of dioxyterephthalic ester from succinosuccinic
ester, unless we make the assumption that the transformation of these
substances is attended by a migration of the substituent groups. For
succinosuccinic ester, formed by the action of sodium on two molecules
of succinic ester, has either of the formulae (I) or (II); oxidation
of the free acid gives dioxyterephthalic acid in which the
para-positions must remain substituted as in (I) and (II). By
projecting Ladenburg's prism on a plane and numbering the atoms so as
to correspond with Kekule's form, viz. that 1.2 and 1.6 should be
ortho-positions, 1.3 and 1.5 meta-, and 1.4 para-, and following out
the transformation on the Ladenburg formula, then an
ortho-dioxyterephthalic acid (IV) should result, a fact denied by
experience, and inexplicable unless we assume a wandering of atoms.
Kekule's formula (III), on the other hand, is in full agreement
(Baeyer). This explanation has been challenged by Ladenburg (_Ber._,
1886, 19, p. 971; _Ber._, 1887, 20, p. 62) and by A.K. Miller (_J.C.S.
Trans._, 1887, p. 208). The transformation is not one of the oxidation
of a hexamethylene compound to a benzenoid compound, for only two
hydrogen atoms are removed. Succinosuccinic ester behaves both as a
ketone and as a phenol, thereby exhibiting desmotropy; assuming the
ketone formula as indicating the constitution, then in Baeyer's
equation we have a migration of a hydrogen atom, whereas to bring
Ladenburg's formula into line, an oxygen atom must migrate.

The relative merits of the formulae of Kekule, Claus and Dewar were
next investigated by means of the reduction products of benzene, it
being Baeyer's intention to detect whether double linkages were or
were not present in the benzene complex.

To follow Baeyer's results we must explain his nomenclature of the
reduced benzene derivatives. He numbers the carbon atoms placed at the
corners of a hexagon from 1 to 6, and each side in the same order, so
that the carbon atoms 1 and 2 are connected by the side 1, atoms 2 and
3 by the side 2, and so on. A doubly linked pair of atoms is denoted
by the sign [DELTA] with the index corresponding to the side; if there
are two pairs of double links, then indices corresponding to both
sides are employed. Thus [DELTA]^1 denotes a tetrahydro derivative in
which the double link occupies the side 1; [DELTA]^{1.3}, a dihydro
derivative, the double links being along the sides 1 and 3. Another
form of isomerism is occasioned by spatial arrangements, many of the
_reduced_ terephthalic acids existing in two stereo-isomeric forms.
Baeyer explains this by analogy with fumaric and maleic acids: he
assumes the reduced benzene ring to lie in a plane; when both carboxyl
groups are on the same side of this plane, the acids, in general,
resemble maleic acids, these forms he denotes by [GAMMA]_cis-cis_, or
shortly _cis_-; when the carboxyl groups are on opposite sides, the
acids correspond to fumaric acid, these forms are denoted by
[GAMMA]_cis-trans_, or shortly _trans_-.

By reducing terephthalic acid with sodium amalgam, care being taken to
neutralize the caustic soda simultaneously formed by passing in carbon
dioxide, [DELTA]^{2.5} dihydroterephthalic acid is obtained; this
results from the splitting of a _para_-linkage. By boiling with water
the [DELTA]^{2.5} acid is converted into the [DELTA]^{1.5}
dihydroterephthalic acid. This acid is converted into the
[DELTA]^{1.4} acid by soda, and into the [DELTA]^2 tetrahydro acid by
reduction. From this acid the [DELTA]^{1.3} dihydro and the [DELTA]^1
tetrahydro acids may be obtained, from both of which the hexahydro
acid may be prepared. From these results Baeyer concluded that Claus'
formula with three para-linkings cannot possibly be correct, for the
[DELTA]^{2.5} dihydroterephthalic acid undoubtedly has two ethylene
linkages, since it readily takes up two or four atoms of bromine, and
is oxidized in warm aqueous solution by alkaline potassium
permanganate. But the formation of the [DELTA]^{2.5} acid as the first
reduction product is not fully consistent with Kekule's symbol, for we
should then expect the [DELTA]^{1.3} or the [DELTA]^{1.5} acid to be
first formed (see also POLYMETHYLENES).

The stronger argument against the ethylenoid linkages demanded by Kekule's formula is provided by the remarkable stability towards oxidizing and reducing agents which characterizes all benzenoid compounds. From the fact that reduction products containing either one or two double linkages behave exactly as unsaturated aliphatic compounds, being readily reduced or oxidized, and combining with the halogen elements and haloid acids, it seems probable that in benzenoid compounds the fourth valencies are symmetrically distributed in such a manner as to induce a peculiar stability in the molecule. Such a configuration was proposed in 1887 by H.E. Armstrong (_J.C.S. Trans._, 1887, p. 258), and shortly afterwards by Baeyer (_Ann._, 1888, 245, p. 103). In this formula, the so-called "centric formula," the assumption made is that the fourth valencies are simply _directed_ towards the centre of the ring; nothing further is said about the fourth valencies except that they exert a pressure towards the centre. Claus maintained that Baeyer's view was identical with his own, for as in Baeyer's formula, the fourth valencies have a different function from the peripheral valencies, being united at the centre in a form of potential union.

It is difficult to determine which configuration most accurately explains the observed facts; Kekule's formula undoubtedly explains the synthetical production of benzenoid compounds most satisfactorily, and W. Marckwald (_Ann._, 1893, 274, p. 331; 1894, 279, p. 14) has supported this formula from considerations based on the syntheses of the quinoline ring. Further researches by Baeyer, and upon various nitrogenous ring systems by E. Bamberger (a strong supporter of the centric formula), have shown that the nature of the substituent groups influences the distribution of the fourth valencies; therefore it may be concluded that in compounds the benzene nucleus appears to be capable of existence in two tautomeric forms, in the sense that each particular derivative possesses a definite constitution. The benzene nucleus presents a remarkable case, which must be considered in the formulation of any complete theory of valency. From a study of the reduction of compounds containing two ethylenic bonds united by a single bond, termed a "conjugated system," E. Thiele suggested a doctrine of "partial valencies," which assumes that in addition to the ordinary valencies, each doubly linked atom has a partial valency, by which the atom first interacts. When applied to benzene, a twofold conjugated system is suggested in which the partial valencies of adjacent atoms neutralize, with the formation of a potential double link. The stability of benzene is ascribed to this conjugation.[14]

Physico-chemical methods.

Physico-chemical properties have also been drawn upon to decide whether double unions are present in the benzene complex; but here the predilections of the observers apparently influence the nature of the conclusions to be drawn from such data. It is well known that singly, doubly and trebly linked carbon atoms affect the physical properties of substances, such as the refractive index, specific volume, and the heat of combustion; and by determining these constants for many substances, fairly definite values can be assigned to these groupings. The general question of the relation of the refractive index to constitution has been especially studied by J.W. Bruhl, who concluded that benzene contained 3 double linkages; whereas, in 1901, Pellini (_Gazetta_, 31, i. p. 1) calculated that 9 single linkages were present. A similar contradiction apparently exists with regard to the specific volume, for while benzene has a specific volume corresponding to Claus' formula, toluene, or methylbenzene, rather points to Kekule's. The heat of combustion, as first determined by Julius Thomsen, agreed rather better with the presence of nine single unions. His work was repeated on a finer scale by M.P.E. Berthelot of Paris, and F.C.A. Stohmann of Leipzig; and the new data and the conclusions to be drawn from them formed the subject of much discussion, Bruhl endeavouring to show how they supported Kekule's formula, while Thomsen maintained that they demanded the benzene union to have a different heat of combustion from the acetylene union. Thomsen then investigated heats of combustion of various benzenoid hydrocarbons--benzene, naphthalene, anthracene, phenanthrene, &c.--in the crystallized state. It was found that the results were capable of expression by the empirical relation C_{a}H_{2b} = 104.3b + 49.09m + 105.47n, where C_{a}H_{2b} denotes the formula of the hydrocarbon, m the number of single carbon linkings and n the number of double linkings, m and n being calculated on the Kekule formulae. But, at the same time, the constants in the above relation are not identical with those in the corresponding relation empirically deduced from observations on fatty hydrocarbons; and we are therefore led to conclude that a benzene union is considerably more stable than an ethylene union.

Mention may be made of the absorption spectrum of benzene. According to W.N. Hartley (_J.C.S._, 1905, 87, p. 1822), there are six bands in the ultra-violet, while E.C.C. Baly and J.N. Collie (_J.C.S._, 1905, 87, p. 1332; 1906, 89, p. 524) record seven. These bands are due to molecular oscillations; Hartley suggests the carbon atoms to be rotating and forming alternately single and double linkages, the formation of three double links giving three bands, and of three single links another three; Baly and Collie, on the other hand, suggest the making and breaking of links between adjacent atoms, pointing out that there are seven combinations of one, two and three pairs of carbon atoms in the benzene molecule.

_Stereo-chemical Configurations._--Simultaneously with the discussions of Kekule, Ladenburg, Claus, Baeyer and others as to the merits of various plane formulae of the benzene complex, there were published many suggestions with regard to the arrangement of the atoms in space, all of which attempted to explain the number of isomers and the equivalence of the hydrogen atoms. The development of stereo-isomerism at the hands of J. Wislicenus, Le Bel and van 't Hoff has resulted in the introduction of another condition which formulae for the benzene complex must satisfy, viz. that the hydrogen atoms must all lie in one plane. The proof of this statement rests on the fact that if the hydrogen atoms were not co-planar, then substitution derivatives (the substituting groups not containing asymmetric carbon atoms) should exist in enantiomorphic forms, differing in crystal form and in their action on polarized light; such optical antipodes have, however, not yet been separated. Ladenburg's prism formula would give two enantiomorphic ortho-di-substitution derivatives; while forms in which the hydrogen atoms are placed at the corners of a regular octahedron would yield enantiomorphic tri-substitution derivatives.

The octahedral formula discussed by Julius Thomsen (_Ber._, 1886, 19,
p. 2944) consists of the six carbon atoms placed at the corners of a
regular octahedron, and connected together by the full lines as shown
in (I); a plane projection gives a hexagon with diagonals (II).
Reduction to hexamethylene compounds necessitates the disruption of
three of the edges of the octahedron, the diagonal linkings remaining
intact, or, in the plane projection, three peripheral linkages, the
hexamethylene ring assuming the form (III):

In 1888 J.E. Marsh published a paper (_Phil. Mag._ [V.], 26, p. 426)
in which he discussed various stereo-chemical representations of the
benzene nucleus. (The stereo-chemistry of carbon compounds has led to
the spatial representation of a carbon atom as being situated at the
centre of a tetrahedron, the four valencies being directed towards the
apices; see above, and ISOMERISM.) A form based on Kekule's formula
consists in taking three pairs of tetrahedra, each pair having a side
in common, and joining them up along the sides of a regular hexagon by
means of their apices. This form, afterwards supported by Carl Graebe
(_Ber._, 1902, 35, p. 526; see also Marsh's reply, _Journ. Chem. Soc.
Trans._, 1902, p. 961) shows the proximity of the ortho-positions, but
fails to explain the identity of 1.2 and 1.6 compounds. Arrangements
connected with Claus' formula are obtained by placing six tetrahedra
on the six triangles formed by the diagonals of a plane hexagon. The
form in which the tetrahedra are all on one side, afterwards discussed
by J. Loschmidt (_Monats._, 1890, II, p. 28), would not give
stereo-isomers; and the arrangement of placing the tetrahedra on
alternate sides, a form afterwards developed by W. Vaubel (_Journ. Pr.
Chem._, 1894[2], 49, p. 308), has the advantage of bringing the
meta-positions on one side, and the ortho- and para- on opposite
sides, thus exhibiting the similarity actually observed between these
series of compounds. Marsh also devised a form closely resembling that
of Thomsen, inasmuch as the carbon atoms occupied the angles of a
regular octahedron, and the diagonal linkages differed in nature from
the peripheral, but differing from Thomsen's since rupture of the
diagonal and not peripheral bonds accompanied the reduction to
hexamethylene.

We may also notice the model devised by H. Sachse (_Ber._, 1888, 21,
2530; _Zeit. fur phys. Chem._, II, p. 214; 23, p. 2062). Two parallel
triangular faces are removed from a cardboard model of a regular
octahedron, and on the remaining six faces tetrahedra are then placed;
the hydrogen atoms are at the free angles. This configuration is,
according to Sachse, more stable than any other form; no oscillation
is possible, the molecule being only able to move as a whole. In 1897,
J.N. Collie (_Journ. Chem. Soc. Trans._, p. 1013) considered in detail
an octahedral form, and showed how by means of certain simple
rotations of his system the formulae of Kekule and Claus could be
obtained as projections. An entirely new device, suggested by B. Konig
(_Chem. Zeit._, 1905, 29, p. 30), assumed the six carbon atoms to
occupy six of the corners of a cube, each carbon atom being linked to
a hydrogen atom and by single bonds to two neighbouring carbon atoms,
the remaining valencies being directed to the unoccupied corners of
the cube, three to each, where they are supposed to satisfy each
other.

_Condensed Nuclei._

Restricting ourselves to compounds resulting from the fusion of benzene rings, we have first to consider naphthalene, C10H8, which consists of two benzene rings having a pair of carbon atoms in common. The next members are the isomers anthracene and phenanthrene, C14H10, formed from three benzene nuclei. Here we shall only discuss the structure of these compounds in the light of the modern benzene theories; reference should be made to the articles NAPHTHALENE, ANTHRACENE and PHENANTHRENE for syntheses, decompositions, &c.

_Naphthalene._--Of the earlier suggestions for the constitution of naphthalene we notice the formulae of Wreden (1) and (2), Berthelot and Balls (3), R.A.C.E. Erlenmeyer (4) and Adolf Claus (5).

//\ //\ /|\ /|\ /|\ //\ /\\
// \ // \ / | \ / | \ / | \ // \ / \\
// \ __CH2 // \/ | \ / | \/ | \ // \/ \\
| || | | || | || || | || | || | || |
| || | /||CH | || | || || | || | || | || |
| || |/ || | || | || || | || | || | || |
\\ /---C || \\ /\ | / \ | /\ | / \\ /\ //
\\ / \ || \\ / \ | / \ | / \ | / \\ / \ //
\\/ \||CH \\/ \|/ \|/ \|/ \\/ \//

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

/|\ /|\
/ | \ / | \
|\ | /| | ||
| \|/ | | ||
| | | | ||
| /|\ | | ||
|/ | \| | ||
\ | / \ | /
\|/ \|/

(5)

The first suggestion is quite out of the question. C. Graebe in 1866 (_Ann._ 149, p. 20) established the symmetry of the naphthalene nucleus, and showed that whichever half of the molecule be oxidized the same phthalic acid results. Therefore formula (2), being unsymmetrical, is impossible. The third formula is based on Dewar's benzene formula, which we have seen to be incorrect. Formula (4) is symmetrical and based on Kekule's formula: it is in full accord with the syntheses and decompositions of the naphthalene nucleus and the number of isomers found. In 1882 Claus suggested a combination of his own and Dewar's benzene formulae. This is obviously unsymmetrical, consisting of an aliphatic and an aromatic nucleus; Claus explained the formation of the same phthalic acid from the oxidation of either nucleus by supposing that if the aromatic group be oxidized, the aliphatic residue assumes the character of a benzene nucleus. Bamberger opposed Claus' formula on the following grounds:--The molecule of naphthalene is symmetrical, since 2.7 dioxynaphthalene is readily esterified by methyl iodide and sulphuric acid to a dimethyl ether; and no more than two mono-substitution derivatives are known. The molecule is aromatic but not benzenoid; however, by the reduction of one half of the molecule, the other assumes a benzenoid character.

If [beta]-naphthylamine and [beta]-naphthol be reduced, tetrahydro
products are obtained in which the amino- or oxy-bearing half of the
molecule becomes aliphatic in character. The compounds so obtained,
alicyclic-[beta]-tetrahydronaphthylamine and
alicyclic-[beta]-tetrahydronaphthol, closely resemble
[beta]-aminodiethylbenzene, C6H4(C2H5).C2H4NH2, and
[beta]-oxydiethylbenzene, C6H4(C2H5).C2H4OH. If [alpha]-naphthylamine
and [alpha]-naphthol be reduced, the hydrogen atoms attach themselves
to the non-substituted half of the molecule, and the compounds so
obtained resemble aminodiethylbenzene, C6H3.NH2(C2H5)2 and
oxydiethylbenzene, C6H3.OH(C2H5)2. Bamberger's observations on reduced
quinoline derivatives point to the same conclusion, that condensed
nuclei are not benzenoid, but possess an individual character, which
breaks down, however, when the molecule is reduced.

It remains, therefore, to consider Erlenmeyer's formula and those derived from the centric hypothesis. The former, based on Kekule's symbol for benzene, explains the decompositions and syntheses of the ring, but the character of naphthalene is not in keeping with the presence of five double linkages, although it is more readily acted upon than benzene is. On the centric hypothesis two formulae are possible: (i) due to H.E. Armstrong, and (2) due to E. Bamberger.

/|\ /|\ /|\ /|\
/ \ / \ / \ / \
|\ -|- /| |\ X /|
| | | | / \ |
| | | | |
| | | | \ / |
|/ -|- \| |/ X \|
\ / \ / \ / \ /
\|/ \|/ \|/ \|/

(1) (2)

In the first symbol it is assumed that one of the affinities of each of the two central carbon atoms common to the two rings _acts into_ both rings, an assumption involving a somewhat wide departure from all ordinary views as to the manner in which affinity acts. This symbol harmonizes with the fact that the two rings are in complete sympathy, the one responding to every change made in the other. Then, on account of the relatively slight--because divided--influence which would be exercised upon the two rings by the two affinities common to both, the remaining four centric affinities of each ring would presumably be less attracted into the ring than in the case of benzene; consequently they would be more active outwards, and combination would set in more readily. When, as in the formation of naphthalene tetrachloride, for example, the one ring becomes saturated, the other might be expected to assume the normal centric form and become relatively inactive. This is absolutely the case. On the other hand, if substitution be effected in the one ring, and the affinities in that ring become attracted inwards, as apparently happens in the case of benzene, the adjoining ring should become relatively more active because the common affinities would act less into it. Hence, unless the radical introduced be one which exercises a special attractive influence, substitution should take place in preference in the previously unsubstituted ring. In practice this usually occurs; for example, on further bromination, [alpha]-bromonaphthalene yields a mixture of the (1.4) and (1.5) dibromonaphthalenes; and when nitronaphthalene is either brominated, or nitrated or sulphonated, the action is practically confined to the second ring. The centric formula proposed by Bamberger represents naphthalene as formed by the fusion of two benzene rings, this indicates that it is a monocyclic composed of ten atoms of carbon. The formula has the advantage that it may be constructed from tetrahedral models of the carbon atom; but it involves the assumption that the molecule has within it a mechanism, equivalent in a measure to a system of railway points, which can readily close up and pass into that characteristic of benzene.

_Anthracene and Phenanthrene._--These isomeric hydrocarbons, of the formula C14H10, are to be regarded as formed by the fusion of three benzenoid rings as represented by the symbols:--

____
/\ /\ /\ / \
/ \ / \ / \ ____/ \____
| | | | / \ / \
| | | | / \____/ \
\ / \ / \ / \ / \ /
\/ \/ \/ \____/ \____/

Anthracene Phenanthrene

In both cases the medial ring is most readily attacked; and various formulae have been devised which are claimed by their authors to represent this and other facts. According to Armstrong, anthracene behaves unsymmetrically towards substituents, and hence one lateral ring differs from the other; he represents the molecule as consisting of one centric ring, the remaining medial and lateral ring being ethenoid. Bamberger, on the other hand, extends his views on benzene and naphthalene and assumes the molecule to be (1). For general purposes, however, the symbol (2), in which the lateral rings are benzenoid and the medial ring fatty, represents quite adequately the syntheses, decompositions, and behaviour of anthracene.

/|\ /|\ /|\ / \ /|\ / \
/ \ / \ / \ / \ / | \ / \
|\ X X /| | | | | |
| / \ / \ | | | | | |
| | | | | | |
| \ / \ / | | | | | |
|/ X X \| | | | | |
\ / \ / \ / \ / \ | / \ /
\|/ \|/ \|/ \ / \|/ \ /

(1) (2)

Phenanthrene is regarded by Armstrong as represented by (3), the lateral rings being benzenoid, and the medial ring fatty; Bamberger, however, regards it as (4), the molecule being entirely aromatic. An interesting observation by Baeyer, viz. that stilbene, C6H5.CH:CH.C6H5, is very readily oxidized, while phenanthrene is not, supports, in some measure, the views of Bamberger.

____ ____
/----\ /\ /\
____/ \____ ____/_ _\____
/ \ / \ /\ / \ /\
/ \____/ \ / __/__\__ \
\ / \ / \ / \ /
\____/ \____/ \/__\/ \/__\/

(3) (4)

_Heterocyclic Compounds._

During recent years an immense number of ringed or cyclic compounds have been discovered, which exhibit individual characters more closely resembling benzene, naphthalene, &c. than purely aliphatic substances, inasmuch as in general they contain double linkages, yet withstand oxidation, and behave as nuclei, forming derivatives in much the same way as benzene. By reduction, the double linkages become saturated, and compounds result which stand in much about the same relation to the original nucleus as hexamethylene does to benzene. In general, therefore, it may be considered that the double linkages are not of exactly the same nature as the double linkage present in ethylene and ethylenoid compounds, but that they are analogous to the potential valencies of benzene. The centric hypothesis has been applied to these rings by Bamberger and others; but as in the previous rings considered, the ordinary representation with double and single linkages generally represents the syntheses, decompositions, &c.; exceptions, however, are known where it is necessary to assume an oscillation of the double linkage. Five- and six-membered rings are the most stable and important, the last-named group resulting from the polymerization of many substances; three- and four-membered rings are formed with difficulty, and are easily ruptured; rings containing seven or more members are generally unstable, and are relatively little known. The elements which go to form heterocyclic rings, in addition to carbon, are oxygen, sulphur, selenium and nitrogen. It is remarkable that sulphur can replace two methine or CH groups with the production of compounds greatly resembling, the original one. Thus benzene, (CH)6, gives thiophene, (CH)4S, from which it is difficultly distinguished; pyridine, (CH)5N, gives thiazole, (CH)3.N.S, which is a very similar substance; naphthalene gives thionaphthen, C8H6S, with which it shows great analogies, especially in the derivatives. Similarly a CH group may be replaced by a nitrogen atom with the production of compounds of similar stability; thus benzene gives pyridine, naphthalene gives quinoline and isoquinoline; anthracene gives acridine and [alpha] and [beta] anthrapyridines. Similarly, two or more methine groups may be replaced by the same number of nitrogen atoms with the formation of rings of considerable stability.

Most of the simple ring systems which contain two adjacent carbon
atoms may suffer fusion with any other ring (also containing two
adjacent carbon atoms) with the production of nuclei of greater
complexity. Such _condensed nuclei_ are, in many cases, more readily
obtained than the parent nucleus. The more important types are derived
from aromatic nuclei, benzene, naphthalene, &c.; the
ortho-di-derivatives of the first named, lending themselves
particularly to the formation of condensed nuclei. Thus
ortho-phenylene diamine yields the following products:--

/\ N /\ N /\ N
/ \ /\\ / \ /\\ / \ /|\
| | \\ | | \\ | | | \
| | CH | | N | | | S
| | / | | / | | | /
\ / \ / \ / \ / \ / \|/
\/ NH , \/ NH , \/ N ,

Benzimidazole Azimidobenzene Benzpiazthiole

/\ NH /\ NH /\ N
/ \ / \ / \ /\\ / \ /\\
| | \ | | \\ | | CH
| | >CO or | | C.OH | | |
| | / | | / | | CH
\ / \ / \ / \ / \ / \//
\/ NH \/ NH , \/ N

\_______________________________/
Benzimidazolone Quinoxaline

In some cases oxidation of condensed benzenoid-heterocyclic nuclei
results in the rupture of the heterocyclic ring with the formation of
a benzene dicarboxylic acid; but if the aromatic nucleus be weakened
by the introduction of an amino group, then it is the benzenoid
nucleus which is destroyed and a dicarboxylic acid of the heterocyclic
ring system obtained.

Heterocyclic rings may be systematically surveyed from two aspects: (1) by arranging the rings with similar hetero-atoms according to the increasing number of carbon atoms, the so-called "homologous series"; or (2) by first dividing the ring systems according to the number of members constituting the ring, and then classifying these groups according to the nature of the hetero-atoms, the so-called "isologous series." The second method possesses greater advantages, for rings of approximate stability come in one group, and, consequently, their derivatives may be expected to exhibit considerable analogies.

As a useful preliminary it is convenient to divide heterocyclic ring systems into two leading groups: (1) systems resulting from simple internal dehydration (or similar condensations) of saturated aliphatic compounds--such compounds are: the internal anhydrides or cyclic ethers of the glycols and thioglycols (ethylene oxide, &c.); the cyclic alkyleneimides resulting from the splitting off of ammonia between the amino groups of diamino-paraffins (pyrrolidine, piperazine, &c.); the cyclic esters of oxycarboxylic acids (lactones, lactides); the internal anhydrides of aminocarboxylic acids (lactams, betaines); cyclic derivatives of dicarboxylic acids (anhydrides, imides, alkylen-esters, alkylen-amides, &c.). These compounds retain their aliphatic nature, and are best classified with open-chain compounds, into which, in general, they are readily converted. (2) Systems which are generally unsaturated compounds, often of considerable stability, and behave as nuclei; these compounds constitute a well-individualized class exhibiting closer affinities to benzenoid substances than to the open-chain series.

The transition between the two classes as differentiated above may be
illustrated by the following cyclic compounds, each of which contains
a ring composed of four carbon atoms and one oxygen atom:

CH2.CH2\ CH2.CO \ CH2.CO\ CH.CO\ CH=CH\
| O | O | O || O | O
CH2.CH2/ CH2.CH2/ CH2.CO/ CH.CO/ CH=CH/

Tetramethylene Butyrolactone. Succinic Maleic Furfurane.
oxide. anhydride. anhydride.

The first four substances are readily formed from, and converted into,
the corresponding dihydroxy open-chain compound; these substances are
truly aliphatic in character. The fifth compound, on the other hand,
does not behave as an unsaturated aliphatic compound, but its
deportment is that of a nucleus, many substitution derivatives being
capable of synthesis. Reduction, however, converts it into an
aliphatic compound. This is comparable with the reduction of the
benzene nucleus into hexamethylene, a substance of an aliphatic
character.

True ring systems, which possess the characters of organic nuclei, do not come into existence in three-and four-membered rings, their first appearance being in penta-atomic rings. The three primary members are furfurane, thiophene and pyrrol, each of which contains four methine or CH groups, and an oxygen, sulphur and imido (NH) member respectively; a series of compounds containing selenium is also known. The formulae of these substances are:

CH=CH\ CH=CH\ CH=CH\ CH=CH\
| O | S | Se | NH
CH=CH/ CH=CH/ CH=CH/ CH=CH/

Furfurane. Thiophene. Selenophene. Pyrrol.

By substituting one or more CH groups in these compounds by nitrogen atoms, ring-systems, collectively known as _azoles_, result. Obviously, isomeric ring-systems are possible, since the carbon atoms in the original rings are not all of equal value. Thus furfurane yields the following rings by the introduction of one and two nitrogen atoms:

CH==N\ N==CH\ N===N\
| O | O | O
CH=CH/ CH=CH/ CH=CH/

Isoxazole. Oxazole. Diazo-oxides.

CH=N\ N=CH\ N=CH\
| O | O | O
CH=N/ CH=N/ N=CH/

Furazane. Azoximes. Oxybiazole.

Thiophene yields a similar series: isothiazole (only known as the condensed ring, isobenzothiazole), thiazole, diazosulphides, piazthioles, azosulphimes and thiobiazole (the formulae are easily derived from the preceding series by replacing oxygen by sulphur). Thiophene also gives rise to triazsulphole, three nitrogen atoms being introduced. Selenophene gives the series: selenazole, diazoselenide and piaselenole, corresponding to oxazole, diazo-oxides and furazane. Pyrrol yields an analogous series: pyrazole, imidazole or glyoxaline, azimide or osotriazole, triazole and tetrazole:

CH==N\ N==CH\ N===N\
| NH | NH | NH
CH=CH/ CH=CH/ CH=CH/

Pyrazole. Imidazole. Azimide.

N=CH\ N==N\
| NH | NH
N=CH/ N=CH/

Triazole. Tetrazole.

Six-membered ring systems can be referred back, in a manner similar to the above, to pyrone, penthiophene and pyridine, the substances containing a ring of five carbon atoms, and an oxygen, sulphur and nitrogen atom respectively. As before, only _true_ ring nuclei, and not internal anhydrides of aliphatic compounds, will be mentioned. From the pyrone ring the following series of compounds are derived (for brevity, the hydrogen atoms are not printed):