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* Oxidations and Reductions in the Animal Body, by H. D. Dakin. Monographs on
Biochemistry : Longmans, Green, 1912.
6 Kempf, Ber., 1905, 38, 3963 ; Austin, Trans. Chem. Soc., 1911, 99, 264.



POLYMERISATION 173

reactions of organic compounds, mention should be made of * halogen
carriers', which accelerate in a remarkable degree the process of
chlorination and bromination. Among the more important are iron
and its salts, the chlorides and bromides of antimony, molybdenum,
aluminium, and phosphorus, sulphur and iodine.

Catalytic Condensation, such as the Friedel-Crafts reaction, is
discussed under condensation (p. 195).

Polymerisation. The term polymerisation is clearly marked out
from the process dealt with in a succeeding section on condensation
by the nature of the product. A polymerisation product is one
formed by the union of two or more molecules of the original com-
pound in such a manner that depolymerisation, or cleavage into the
original substance, is easily effected. The conversion of acetaldehyde
C 2 H 4 into paraldehyde (C 2 H 4 0) 3 is an example of polymerisation,
for the latter on distillation with a small quantity of sulphuric acid
yields the parent substance. Aldol (C 2 H 4 O) 2 , on the other hand,
cannot be broken up readily into acetaldehyde. The difference lies
in the nature of the link between the molecules : in paraldehyde it is
supposed to be effected by means of oxygen, in aldol by means of
carbon.

CH 3

CH

CH 3 . CH(OH) . CH 2 . CHO
CH 3 . HcLJcH . CH 3 Aldoh

O

Paraldehyde.

The property of undergoing polymerisation is peculiar to un-
saturated compounds, from a natural tendency to saturate themselves.
The formation of diisobutylene from isobutylene under the action of
sulphuric acid or zinc chloride and that of benzene from acetylene
must be included under condensation processes in accordance with
the definition adopted above ; but the conversion of aldehydes into
the polymolecular paraldehytles, and the thio-aldehydes and -ketones
into trithioaldehydes and trithioketones are examples of polymerisa-
tion. Polymerisation of the aldehydes is effected by small quantities
of catalysts, such as mineral acids and certain metallic chlorides.

The change is also exhibited by aromatic aldehydes when acted upon
by alkalis, but in this case intramolecular change occurs and an ester
is formed. Benzaldehyde yields benzyl benzoate.

2C 6 H 6 OHO - C C H 5 CH 2 . OC . C G H fi .



174 CATALYTIC REACTIONS OF ORGANIC COMPOUNDS

The only ketone which undergoes this change is acetone, which in
presence of alkali yields diacetone alcohol CH 3 .CO.CH 2 .C(OH).(CH 3 ) 2 ,
but breaks up on heating into acetone. The thio-aldehydes and
-ketones polymerise so much more readily than the aldehydes
that by acting on the aldehyde or ketone with hydrogen sulphide in
presence of hydrochloric acid polymerisation occurs in process of
formation.

Polymerisation is very commonly observed among cyanogen com-
pounds. Cyanogen itself yields paracyanogen (CN)w, hydrocyanic
acid in alkaline solution deposits on standing a brown amorphous
compound, which* is probably aminomalonic nitrile (CN), . CHNH 2 ,
whilst the alkyl cyanides yield di- and tri-molecular compounds.
Liquid cyanogen chloride gives the solid tricyanogen chloride,
cyanamide forms di- and tri-cyanamide (melamine). Cyanic acid and
its esters also polymerise readily. Thiocyanic acid behaves like
cyanic acid.

Light will sometimes effect polymerisation, as in the conversion of
anthracene into dianthracene (see Part II, p. 149).



CHAIN AND RING FORMATION
I. CONDENSATION, UNION OF CARBON AND CARBON

The terms condensation and condensation product imply a process
and its result which have never been clearly defined, but which at
the same time convey a distinct idea. Thus, the combination of
ethyl alcohol and acetic acid to form an ester a reaction in which
water is separated would not be termed condensation, yet the union
of two molecules of acetaldehyde to form crotonic aldehyde, in which
water is likewise removed, would be regarded as a typical example
of such a process.

CH 3 .COOH + C 2 H 5 OH = CH 3 . COOC 2 H 5 + H 2 O

Acetic acid. Ethyl alcohol. Ethyl acetate.

CH 3 . CHO + CH 3 . CHO = CH 3 . CH : CH . CHO + H 2

Acetaldehyde. Crotonic aldehyde.

Again, all reactions, of which the conversion of aldehyde into aldol
may be taken as the type, are termed aldol condensations, but in thia
case no water is separated.

CH 3 . CHO + CH 3 . CHO = CH 3 . CH(OH) . CH 2 . CHO

Acetaldehyde. Aldol.



CONDENSATION 175

It is easy to draw a distinction between the formation of acetic
ester from alcohol and acetic acid and that of crotonic aldehyde from
acetaldehyde. In the first reaction the two molecules are linked in
the new product by oxygen and are again readily separated by
hydrolysis ; but in the second reaction the new linkage is established
between carbon atoms, and the product is consequently of a much
more stable character. This might help us to a definition, were it
not that in the third example no water is eliminated, although the
new combination is effected between carbon atoms.

Although it is true that the formation of aldol is covered by the
term polymerisation and should, strictly speaking, be included in this
category, yet it is distinct from the process which gives rise to
paraldehyde, a compound which, unlike aldol, is readily dissociated
into the original aldehyde. In other words, the one is a reversible.
the other is practically a non-reversible process.

As the formation of aldol is intimately linked with that of crotonic
aldehyde, it would be illogical to draw distinctions between the two
processes, and the term aldol condensation is therefore justified.

Condensation may then be defined as the union of two or more
organic molecules or parts of the same molecule (with or without
elimination of component elements) in which the new combination is
effected between carbon atoms.

If this definition is accepted it will naturally embrace every kind
of reaction in which new organic compounds are elaborated by the
linking of carbon atoms. Used in this sense the word condensation
can be conveniently applied to denote a certain section of the more
comprehensive category of constructive chemical changes which are
included in the term synthesis.

There is no intention of implying that the combination between
carbon atoms is subject to different conditions from those obtaining
among other elements. The union is, as a rule, more stable, but not
necessarily so, and many reversible changes are known, in which
carbon atoms part company as well as combine. We shall see
presently that an almost equally stable union may be effected between
carbon-nitrogen, carbon-oxygen, or carbon-sulphur, both in open
chain and ring structures.

It must be recognised, therefore, that the distinction is an artificial
one and merely convenient. Also, for convenience, it is desirable to
distinguish between external condensation, in which two or more
different molecules become linked together, and internal condensation,
in which carbon atoms in the same molecule combine, leading to
ring formation.



176 CHAIN AND RING FORMATION

The process of condensation is connected with the early history of
organic chemistry and was the outcome of the first systematic
attempts at organic synthesis.

In the following pages it is intended to give a general survey of
the principal condensation processes,

Nature of Condensation Processes. The examples of condensa-
tion (of which ring formation may be regarded as a special case) are
so numerous and at the same time so varied in character that it
would be impossible within the limits of a single chapter to
enumerate them in anything like detail. Nevertheless, it is possible
to lay down certain broad generalisations under which the different
reactions may be grouped.

In the first place it will be observed that union between molecules
or parts of a molecule is nearly always determined by unsaturation
and by a consequent tendency for the unsaturated atoms to saturate
themselves. On this basis condensation processes may be roughly
divided into two groups : those in which the combining molecules
Are induced to unite by being rendered, as it were, artificially
unsaturated as the result of withdrawing certain elements, and those
which, being already unsaturated, combine either spontaneously or
with the help of a reagent or catalyst.

To the first category belong those substances which, either by the
.action of heat or oxygen, lose hydrogen, resulting in the union of
the residual groups. The linking up of compounds by the removal
of halogen by the aid of a metal is illustrated by the processes of
Fittig and Wurtz in chain formation, and by that of Freund and
Perkin in the preparation of ring structures. Condensation effected
by the separation of halogen acid through the action of catalysts is
represented by the Friedel-Crafts method with aluminium and ferric
.chlorides, and by that of Ullmanu with finely divided copper. The
removal of carbon dioxide by heating barium or calcium salts of
organic acids or their anhydrides and by electrolysis gives rise in
the first case to ketones and in the second to paraffins and new
homologous acids.

It is, however, to the second category, namely the union of
unsaturated compounds, that the largest number of condensation
processes belong. They may be divided broadly into those in which
the combining molecules are both unsaturated, as in the union of
.acetylene with itself to form benzene, and those in which one
molecule is saturated and the other not, as in Michael's, Reformatsky's,
.and Grignard's reactions (pp. 202-208).



NATURE OF CONDENSATION PROCESSES 177

But the process which has afforded the most varied and extended
application is one which, for want of a better name, may be termed
intermolecular isomeric change. In the chapter on isomeric change,
Part II, chap, vi, the various types of change are enumerated and
illustrated. These changes are brought about by the wandering of a
hydrogen atom from one polyvalent atom to another in the molecule,
accompanied by change of linkage. Suppose a similar process to
take place between two polyvalent atoms belonging to different
molecules, such a reaction would bring about mutual unsaturation,
resulting in a union between them.

For example, the most common case of dynamic isomerism is
the keto-enol change, which takes place when a hydrogen atom
wanders from a carbon atom to a neighbouring oxygen atom.

O:C.CH ^ HO.C:C

I XX I XX

Now if this change occurs between two molecules, one of which

contains a CO group and the other a CH 2 group, as in the formation

of aldol, we have a typical example of this kind of condensation,

0:C + CH 2 -> HO.C CH -> C = C

XX XX II XX XN

a process which may or may not be followed by the removal ot
water and the production of an unsaturated compound.

Many examples of similar intermolecular isomeric changes occur,
as for instance in Thorpe's reaction (p. 252), where the union of
cyanogen derivatives with CH 2 groups takes place.
N;C+CH 2 -^ HN:C CH

I XX II

Michael's reaction might be included in the same category, corre-
sponding to a shifting of the hydrogen atom within the molecule of
an unsaturated hydrocarbon radical (see p. 202).

CH 2 + CH : CH - CH CH CH 2

XX I I XX I I

If we consider the various types of isomeric change and the large
number of compounds which they include, the wide range and
variety of the condensation products to which the above process
may be applied will be easily realised. At the same time it is restricted
in its application, being dependent mainly on the vicinity of certain
active (usually negative) groups, and, to a smaller degree, on the
nature of the condensing agent. A paraffin, although it contains
numerous CH 2 groups, does not undergo condensation of the aldol
type with an aldehyde or ketone under any conditions. Formaldehyde,



17S CHAIN AND RING FORMATION

the most reactive of these substances, which readily condenses with
aromatic hydrocarbons, cannot be induced to combine with methane
or its hornologues unless a negative group such as CO, CN, N0. 2
replaces at least one atom of hydrogen in the paraffin. The
acetoacetic ester synthesis, in which two esters unite under the
influence of metallic sodium or sodium ethoxide, is undoubtedly an
additive process, although resulting in the separation of a molecule
of alcohol. It may be given the following general form :

/OH
R.CO.OC 2 H + CH,X -> R.C-CHX - >



R . CO . CH . X + C 2 H 5 OH

The X in the formula stands for an acid radical which may be not
only an ester group, but an aldehyde, ketone, cyanogen, nitro or
unsaturated ester or ketone group, HC : CH . CO.

The aldol and benzoin condensations and Claisen reactions consist
in the union of two molecules of aldehyde, frequently followed by
the removal of water and formation of an unsaturated aldehyde, as
already explained.

R.CHO + CHCO - RHC(OH) . CH . CO -^ RHC:C.C:O

ii i . i

Here again the CO group in the CH 2 . CO complex may be replaced
by carboxyl (Perkin's reaction), carbethoxyl, and the other negative
groups mentioned above, whilst the aldehyde may be substituted
by a ketone (Claisen's and Knoevenagel's reactions, pp. 238, 241).

Ring Formation. Nearly all the above reactions may become
intramolecular if the necessary grouping is present, and in such
cases ring formation follows. But the process in some cases is
subject to certain limitations, which depend on the number of atoms
composing the ring. The acetoacetic ester synthesis, for example,
may be applied intramolecularly to adipic, pimelic, and suberic esters,
but not to glutaric or succinic esters.

CH 2 . CH 2 . COOC 2 H 5 CH 2 . CH 2

CO + C 2 H 5 OH

CH 2 . CH 2 . COOC 2 H 5 CH 2 . CH . COOR

In other words, it is possible to form a 5, 6, and 7 carbon ring,
but not one of three or four carbon atoms.

Baeyer's Strain Theory. The commonest type of cyclic com-
pounds occurring in nature are those consisting of 5 or 6 atoms.



BAEYER'S STRAIN THEORY 179

and, as a matter of experience, they are of all ring structures the
most readily produced, and the most stable under the action of heat
and reagents.

An ingenious and very plausible explanation has been advanced
by Baeyer under the name of the Strain (Spannung] Theory, which
is based upon stereochemical considerations. Supposing the four
valencies of carbon to be directed towards the solid angles of a
regular tetrahedron, they will make angles of 109 28' with one
another. Any distortion or deviation of these valency directions
will lead, according to the theory, to a condition of strain which will
make itself evident by loss of stability, and the greater the strain
the greater the instability.

Baeyer regards an olefine as the first member of the cyclic series,
in which the normal position of the two bonds uniting the carbon
atoms is assumed to be bent so as to form straight parallel links
between the atoms. The amount of distortion can be estimated, for
each bond is bent inwards through half the total angle which the
two make with one another, J (109 28') = 54 44'; in a cyclopro-
pane derivative, in which the carbon atoms may be supposed to
make an equilateral triangle, the amount of displacement will be
J (109 28' -60) = 24 44'. The amount of deviation from the
normal is given in the following table :

Cycloethane (Ethylene) (109 28') 54 44'

Cyclopropane \ ( 1 09 28' - 60) 24 44'

Cyclobutane fc (109 28' - 90) 9 44'

Cyclopentane $ (109 -28' -108) 44'

Cyclohexane ,109 28' -120) -5 16'

Cycloheptane (109 28' - 128 34') - 9 33'

Cyclooctane $ (109 28' -135) -12 46'

It will be seen that the condition of greatest strain will occur
in the olefine, that of least strain in the cyclopentanes, and then in
the cyclohexanes. In the last three the strain will be outwards
instead of inwards.

Stability of Ring Structures. We will now consider briefly to
what extent the experimental facts harmonise with Baeyer's theory.
It should be stated at the outset that the theory has reference to
cycle-paraffins and their derivatives, but does not necessarily include
aromatic compounds or heterocyclic systems, which will be considered
separately ; for the unsaturated nature of the aromatic nucleus and
the presence of other atoms than carbon in the ring may, and
probably do, affect the stability of the system. No great importance
need therefore be attached to an observation such as that of
Markownikoff, who found that a cyclopentane derivative on

N2



180 CHAIN AND RING FORMATION

bromination in presence of aluminium bromide is converted into
a brominated benzene.

At the same time it is a significant fact that among heterocyclic,
as well as homocyclic compounds, 5 and 6 atom rings are not only
most easily prepared, but of commonest occurrence among natural
products derived from animal and plant organisms. Although there
are certain facts not in harmony with the theory, which, as Aschan 1
says, cannot be elevated to the position of a law, like the theory of
Van 't Hoff and Le Bel, it nevertheless presents a rough picture
of molecular mechanics, which has had the effect of stimulating
inquiry and enriching the science with fruitful results. In studying
the stability of the cycloparaffins and their derivatives, it is important
to remember that this property varies with the nature of the radicals
attached to the cyclic carbon atoms. Kot/, 2 who made a careful
study of the subject, found that the stability of the cyclopropane
ring is diminished by the introduction of alkyl groups and increased
by that of carboxyl. and Buchner 3 has shown that the latter effect
is further enhanced when the carboxyl groups are attached to different
carbon atoms. For example, cyclopropane 1,1, dicarboxylic acid
undergoes disruption in contact with hydrobromic acid in the cold,

CH 2

/\ -* CH 2 Br.CH 2 .CH(C0 2 H) 2

H 2 C C(C0 2 H) a

whereas the 1 . 2 dicarboxylic acid is not affected even when boiled
with the concentrated reagent. The effect of carboxyl on the stability
of 3- and 4-carbon rings is, in short, so great that frequently more
depends on the nature and position of the radicals than on the
number of carbon atoms in the ring. 4

We will consider first the stability of the different cycloparaffins
towards reagents, then the facility with which they are formed, and
finally their conversion into one another.

Action of Reagents. Taking ethylene as representing the first
member of the cyclic series, it is characterised by the ease with
which it unites with halogens, halogen acids, strong sulphuric acid,
and undergoes oxidation with permanganate. These properties,
which are manifested in the hydrocarbon itself, may be modified to
a greater or less extent, as we have seen (p. 116), in certain of its

1 Chemie der alicyklischen Verbindungen, by 0. Aschan. Vieweg, Brunswick, 1905.

2 J. prakt. Chem., 1903, 68, 156. * 3 -Annalen, 1895, 284, 198.

4 Perk in and Simonsen, Trans. Chem. Soc.. 1907, 91, 817; Perkin and Golds-
worthy, Trans. Cliem. Soc., 1914, 105, 2665; Kenner, Trans. Chem. Soc., 1914, 105,
2685.



ACTION OF EEAGENTS 181

derivatives. Cyclopropane combines with bromine in sunlight,
though not so readily as benzene, to form trimethylene bromide ;
it unites quite readily with hydrobromic and hydriodic acids, giving
normal propyl bromide and iodide, and with sulphuric acid, forming
propyl hydrogen sulphate, which on heating with water is converted
into ?2-propyl alcohol. In all these reactions it resembles ethylene,
but differs in its indifference towards permanganate, which is without
action. Cyclopropane is decomposed above 550 (or, as Ipatievv 1
found, at 100 by passing it through a tube filled with iron filings)
and gives propylene. Dimethylcyclopropane is completely converted
into trimethylethylene when passed over alumina at 350.

/CH 2

(CH 3 ) 2 C<J -* (CH 3 ) 2 .C:CH.CH 3
\CH 2

Cyclobutane is inert towards halogens, halogen acids, sulphuric
acid, and permanganate, and is unaffected by heat. Cyclobutanol is,
however, converted by hydrobromic acid into 1 . 3 dibromobutane, 2
H 2 C CH 2 H 2 C CH 2 CH 2 Br CH 3



H 2 C CHOH H 2 C CHBr CH 2 CHBr

and truxillic acid breaks up on heating into two molecules of
cinnamic acid :

C 6 H 5 CH CH . COOH C 6 H 5 CH : CH . COOH

C G H 5 CH CH . COOH C 6 H 5 CH : CH . COOH

Truxillic acid. Cinnamic acid.

but in these cases the stability of the ring is modified by the presence
of radicals.

In cyclopentane and cyclohexane and their derivatives ring
cleavage is never effected by any of the reagents mentioned above,
unless the ring is already weakened by the attachment of oxygen to
carbon in the form of ketone groups.

Increasing stability of the ring up to five and six atoms of carbon
is also proved by the heat of combustion, which is discussed at greater
length in a later chapter (Part II, p. 68). It is there shown that the
heat of combustion decreases from ethylene to cyclohexane, indicating
increasing stability or decreasing energy content. Stohmann and
Kleber compared the mean difference between the heats of com-
bustion of the cycloparafnns and the paraffins, allowing for the two

1 Ber., 1902, 35, 1063 ; 1903, 36, 2014.
9 Perkin, Trans. Chem. Soc.. 1894, 65, 951.



182 CHAIN AND KING FORMATION

additional hydrogen atoms in the open-chain compound, the results
of which are given in calories in column I, whilst the mean loss of
energy is given in column II.

I II
cals. cals.

Cycloethane (ethylene) 38-1 35-9

Cyclopropane 37-1 31-9

Cyclobutane 39-9 29-1

Cyclopentane 16-1 52-9

Cyclohexane 14-3 54-7

Evidence of Ring Formation. It is well known that certain
general reactions which lead to the formation of 5 and 6 atom rings
fail when it is attempted to produce smaller or larger ring structures.
The acetoacetic ester synthesis when applied to glutaric ester is a case
in point (p. 178). Similarly calcium adipate, pimelate, and suberate
yield respectively cyclopentanone, cyclohexanone, and cycloheptanone
(p. 226), whereas calcium succinate gives in place of cyclopropanone
a cyclic diketone of the double formula l

CH 2 .CO.CH 2

CH 2 .CO.CH 2

Perkin 2 found, from his method of using sodium malonic ester and
a dibromoparaffin in ring formation (p. 192), that whilst the 5-carbon
ring is produced almost quantitatively, the 4- carbon ring is found
in smaller quantity and a still smaller yield of the 3-carbon ring is
obtained. The 6-carbon ring also gave a poorer yield than the
5-carbon ring, whilst the 7-carbon ring was prepared under con-
siderable difficulty.

Another interesting fact of the same order is the action of zinc on
a/3S-tribromobutane .dicarboxylic acid, which might form either
a cyclopropane or cyclobutane derivative. 3 It is exclusively the
second reaction which occurs.

CH 2 Br CH 2

COOH . CBr/ /CHBr . COOH COOH . CBr/NcH . COOH



CH 2 CH 2

An observation pointing in the same direction was made by Thorpe
and Campbell 4 in the case of cyclopropane and cyclobutane cyanacetic
esters, the former, under the action of sodiocyaiiacetic ester, giving
an open chain condensation product, whereas the cyclobutane deriva-
tive combined, but preserved the ring intact.

1 Feist, Ber., 1895, 28, 731. 2 Ber., 1902, 35, 2105.

3 Perkin and Simonsen, Trans. Chem. Soc., 1909, 95, 11C9.

4 Trans. Chem. Soc., 1910, 97, 2418.



TRANSFORMATION OF RING SYSTEMS 183

Experiments have been carried out by Thorpe, Beesley, and Ingold *
to ascertain which of the two types of compound, I or II, would more
easily form a cyclopropane ring.

\ /^ \ /^

120 >C< 107 16' >C< 109 28'



I. II.

For if cyclohexane represents a regular hexagon, the endocyclic
angles must be 120, thereby changing the angle which the exocyclic
carbon atoms make with the cyclic carbon from 109 28' (the normal
angle) to 107 16'. It follows, therefore, from Baeyer's theory that
type I, where the carbon atoms are in closer proximity, should yield
a three-carbon ring more readily than type II.

The two substances submitted to experiment were a-bromocyclo-
hexane diacetic ester representing type I and a-bromo-/3/?-dimethyl
glutaric ester corresponding to type II.

TT r* P'TT ..... : : ..... :

tt - OMj , C H!Br!GOR CH 3V /CHiBr C0 2 R

H(X MX



The result clearly indicated that by removal of hydrogen bromide
type I gave a more easily formed and more stable ring than type II.

Transformation of Ring Systems. One of the most interesting
features of this problem is the evidence of stability furnished by the



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