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even on long shaking. It will be recalled that the corresponding
chloride reacts instantly with water very energetically. If the
mixture be warmed, solution takes place.


In the presence of alkalies, solution takes place much more readily
with the formation of the alkali salts :

CH 3 .CO
CH 3


>0 + 2 NaOH = 2CH 3 .CO.ONa + H 2 O

EXPERIMENT : Mix 5 c.c. of water with -| c.c. of acetic anhy-
dride, and add a little caustic soda solution. On shaking, without
warming, solution takes place.

Anhydrides of high molecular weight react with water with still
greater difficulty, and require a longer heating to convert them into the
corresponding acid.

With alcohols and phenols, the anhydrides form acid-esters on heat-
ing, while the acid-chlorides react at the ordinary temperature :


V) + C 2 H 5 .OH = CH 3 .CO.OC 9 H 5 + CH 3 .CO.OH
CH 3 .CO/


_>0 + C 6 H 5 .OH = CH 3 .CO.OC 6 H 5 + CH 3 .CO.OH

CH 3 . CO/ Phenyl acetate

It is to be noted that one of the two acid radicals in the anhydride is
not available for the purpose of introducing the acetyl group into other
compounds, acetylating, since it passes over into the acid.

EXPERIMENT : 2 c.c. of alcohol are added to i c.c. of acetic anhy-
dride in a test-tube, and heated gently for several minutes. It is
then treated with water and carefully made slightly alkaline. The
acetic ester can be recognised by its characteristic pleasant odour.
If it does not separate from the liquid, it may be treated with
common salt, as in the experiment on page 145.

With ammonia and primary or secondary organic bases, the anhy-
drides react like the chlorides :

CH 3 .COv

NH 3 + >0 = CH 3 .CO.NH 2 + CH 3 .CO.OH

CH 8 .CO/

CH 8 .COv
C 6 H 5 .NH 2 + ^O = C 6 H 5 .NH.CO.CH 3 + CH 3 .CO.OH

CHo. CO/


EXPERIMENT : Add i c.c. of aniline to i c.c. of acetic anhydride,
heat to incipient ebullition, and then, after cooling, add twice the
volume of water. The crystals of acetanilide separate out easily
if the walls of the vessel be rubbed with a glass rod ; these are
filtered off, and may be recrystallised from a little hot water.

The acid-anhydrides can, therefore, be used, like the chlorides, for
the recognition, separation, characterisation, and detection of alcohols,
phenols, and amines.

In order to complete the enumeration of the reactions of the acid-
anhydrides, it may be mentioned briefly that they yield alcohols, and
the intermediate aldehydes when treated with sodium amalgam :

CH 3 .CO\

>0 + H 2 = CH 3 .CHO + CH 3 .CO.OH

CHg.CO/ Aldehyde

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

It is, therefore, possible to pass from the anhydride of an acid to its
aldehyde or alcohol.


EXAMPLE : Acetamide from Ammonium Acetate 1

To 75 grammes of glacial acetic acid heated to 40-50 in a
porcelain dish on a water-bath, finely pulverised ammonium car-
bonate is added (100 grammes will be necessary) until a test-
portion diluted in a watch-glass with water just shows an alkaline
reaction. The viscous mass is warmed on an actively boiling
water-bath to 80-90, until a few drops of it diluted with water
just show an acid reaction ; it is then poured (without the use of
a funnel-tube) directly into two wide bomb-tubes of hard glass,
which have been previously warmed in a flame. A single Volhard
tube (see page 68) is much more convenient. After the por-
tions of substance adhering to the upper end of the tube have
been removed by melting down carefully with a flame, the last
traces are removed with filter-paper, the tube sealed and heated

i B. 15, 979.



for five hours in a bomb-furnace at 2 20-230. * The liquid re-
action product is fractionated under the hood in a distilling-flask
provided with a condenser. There is first obtained a fraction
boiling between 100-130, consisting essentially of acetic acid and
water. The temperature then rises rapidly to 180 (an extension
tube is substituted for the condenser, see page 22), at which
point the acetamide begins to distil. The fraction passing over
between 180-230 is collected in a beaker, cooled by ice water
at the end of the distillation, and the walls are rubbed with a
sharp-edged glass rod ; the crystals separating out are pressed on
a drying plate to remove the liquid impurities. By another dis-
tillation of the pressed-out crystals, the almost pure acetamide
boiling at 223 passes over. Yield, about 40 grammes. The
product thus obtained possesses an odour very characteristic of
mouse excrement ; this is not the odour of pure acetamide, but
of an impurity accompanying it. In order to remove the im-
purity, a portion of the distilled amide is again pressed out on a
drying plate, and then crystallised from ether. There are thus
obtained colourless, odourless crystals, melting at 82.

The reaction involved in the preparation of an amide from the am-
monium salt of the acid is capable of general application. The latter
is subjected to dry distillation, or more conveniently, heated in a sealed
tube at 220-230 for five hours :

CH 3 . CO . ONH 4 = CH, . CO . NH 2 + H 2 O

In order to purify the amide thus obtained, the reaction-mixture may be
fractionated, as in the case of acetamide, or if the amide separates out
in a solid condition, it may be purified by filtering off the impurities and
crystallising. Substituted acid-amides, and especially easily substituted
aromatic amides, e.g. acetanilide, can also be readily obtained by this
method, by heating a mixture of the acid and amine a long time in an
open vessel :

CH 3 . COOH 3 N . C 6 H 5 = CH 3 . CO . NH . C 6 H 5 + H 2 O

Aniline acetate Acetanilide

The ammonium salts of di- and poly-basic acids react in a similar way,

*&' CO.ONH 4 CO.NH 2

I =1 +2H 2


Ammonium oxalate Oxamide

1 Above this temperature the tube is liable to explode.


Concerning further methods of preparation, it may be stated thai
acid-chlorides or anhydrides when treated with ammonia, primary or
secondary bases form acid-amides very easily:

CH 3 .CO.C1 + NH 3 = CH 3 .CO.NH 2


+ NH 3 = CH 3 .CO.NH 8 + CH 8 .CO. OH

The acid-amides may be furthermore obtained by two methods oi
general application: (i), by treating an ethereal salt with ammonia,
and (2), by treating a nitrile with water:

Acetic acid, Boiling-point, 118
Acetamide, 223

Ethyl acetate

CH, . CN + H 2 = CH 3 . CO . NH


The acid-amides are, with the exception of the lowest member,
formamide, H . CO . NH 2 (a liquid), colourless, crystallisable compounds,
the lower members being very easily soluble in water, e.g., acetamide ;
the solubility decreases with the increase of molecular weight, until
finally they become insoluble. The boiling-points of the amides are
much higher than those of the acids :

Proprionicacid, Boiling-point, 141
Proprionamide, 213

While the entrance of an alkyl residue into the ammonia molecule
does not change the basic character of the compound, as will be dis-
cussed more fully under methylamine, the entrance of a negative acid
radical enfeebles the basic properties of the ammonia residue, so that
the acid-amides possess only a very slight basic character. It is true that
a salt corresponding to ammonium chloride CH 3 .CO.NH 2 .HC1
can be prepared from acetamide by the action of hydrochloric acid;
but this shows a strong acid reaction, is unstable, and decomposes
easily into its components. If it is desired to assign to the acid-amides
a definite character, they must be regarded as acids rather than bases.
One of the amido-hydrogen atoms possesses acid properties in that it
may be replaced by metals. The mercury salts of the acid-amides may
be prepared with especial ease, by boiling the solution of the amide
with mercuric oxide :

2CH 3 .CO.NH 2 -r HgO = (CH 3 .CO.NH) 2 Hg + H,O


EXPERIMENT: Some acetamide is dissolved in water, treated
with a little yellow mercuric oxide, and warmed. The latter goes
into solution, and the salt of the formula given above is formed.

The amido-hydrogen atoms can also be replaced by the negative
chlorine and bromine atoms, as well as by the positive metallic atoms.
These substitution compounds are obtained by treating the amide with
chlorine or bromine, in the presence of an alkali :

CH 3 . CO . NHC1 CH 3 . CO . NHBr CH 3 . CO . NBr 2

Acetchloramide Acetbromamide Acetdibromamide

The monohalogen substituted amides are of especial interest, since, on
being warmed with alkalies, they yield primary alkylamines :

CH 3 . CO . NHBr + H 2 O = CH 3 . NH 2 + HBr + CO 2

This important reaction will be taken up later, under the preparation
of methyl amine from acetamide.

In the acid-amides, the acid radical is not firmly united with the
ammonia residue ; this is shown by the fact that they are saponified,
i.e. decomposed into the acid and ammonia, on boiling with water,
more rapidly by warming with alkalies :

CH 3 . CO . NH 2 + H 2 O = CH, . CO . OH + NH 3

EXPERIMENT : Heat some acetamide in a test-tube with caustic
soda solution. A strong ammoniacal odour is given off, while
the solution contains sodium acetate.

If an acid-amide is treated with a dehydrating agent, e.g., phosphorus
pentoxide, it is converted into a nitrile :

CH 3 . CO . NH 2 = CH 3 . CN + H 2 O


The same result is obtained by treating it with phosphorus penta-
chloride ; but in this case the intermediate products, the amide-chlorides
or imide-chlorides are formed :

CH 3 . CO . NH 2 + PC1 5 - CH 3 . CC1 2 . NH 2 + POCL


The very unstable amide-chloride then passes over, with the loss of one
molecule of hydrochloric acid, into the more stable imide-chloride :
CH, . CC1 2 . NH 2 = CH 3 . CC1= NH 4- HC1


And this finally into the nitrile,

CH 3 .CC1=NH = CH 3 .CN + Hd



EXAMPLE : Acetonitrile from Acetamide 1

To 15 grammes of phosphoric anhydride, contained in a small,
dry flask, 10 grammes of dry acetamide are added. After the two
substances are shaken well together, the flask is connected with a
short condenser, and then heated carefully, with a not too large
luminous flame kept in constant motion. The reaction proceeds
with much foaming. After the mixture has been heated a few
minutes, the acetonitrile is then distilled over with a large luminous
flame, kept in constant motion, into the receiver (test-tube). The
distillate is treated with half its volume of water, and then solid
potash is added until it is no longer dissolved by the lower layer
of liquid. The upper layer is removed with a capillary pipette
and distilled, a small amount of phosphoric anhydride being placed
in the fractionating flask for the complete dehydration of the nitrile.
Boiling-point, 82. Yield, about 5 grammes.

If an acid-amide is heated with a dehydrating agent (phosphorus
pentoxide, pentasulphide, or pentachloride), it loses water, and passes
over into the nitrile, e.g. :

CH 3 .CO NH 2 = CH 3 .CEEN + H 2 O


Since, as has just been done, the acid-amide may be made by dehy-
drating the ammonium salt of an acid, thus, in a single operation the
nitrile may be obtained directly from the ammonium salt, if it is treated
with a powerful dehydrating agent, e.g. ammonium acetate heated with
phosphoric anhydride :

CH 3 .COONH 4 = CH 3 .CN + 2H 2 O

The acid-nitriles may also be obtained by heating alkyl iodides (or
bromides, chlorides) with alcoholic potassium cyanide :

CH,|I + K|CN = CH 3 . CN + KI

CH 2 Br CH 9 .CN

| +2KCN=I +2KBr

CH 2 Br CH 2 .CN

____________ Ethylene cyanide

1 A. 64, 33*-


C 6 H 5 . CH 2 . Cl + KCN = C 6 H 5 . CH 2 . CN + KC1

Benzyl chloride Benzyl cyanide

or by the dry distillation of alkyl alkali sulphates with potassium

cyanide :

X O|C 2 H 5 CNJK
SO,/ ~~~fT~ = C 2 H 5 . CN + K 2 SO 4


Ethyl potassium sulphate Proprionitrile

These two reactions differ from those above in that the introduction of
a new atom of carbon is brought about. The nitriles thus appear to be
cyanides of the alkyls, and, therefore, may be equally well designated
as cyanides, e.g. :

CH 3 . CN = Acetonitrile = Methyl cyanide
CgH^CN = Proprionitrile = Ethyl cyanide
etc. etc. etc.

The lower members of the nitrile series are colourless liquids, the
higher members, crystallisable solids ; the solubility in water decreases
with the increase in molecular weights. If they are heated with water
up to 1 80 under pressure, they take up one molecule of water and are
converted into the acid-amides :

CH 3 .CN + H 2 = CH 3 .CO.NH 2

On heating with acids or alkalies, they take up two molecules of water,
and pass over into the ammonium salt as an intermediate product :

CH 3 . CN + 2 H 2 O = CH 3 . COONH 4

which immediately reacts with the alkali or acid, in accordance with
the following equations :

CH 3 .COONH 4 + KOH = CH 3 .COOK + NH 3 + H 2 O
CH 3 .COONH 4 + HC1 = CH 3 .COOH + NH 4 C1

This process is called " saponification."

If nascent hydrogen (e.g. from zinc and sulphuric acid) be allowed
to act on nitriles, primary amines are formed (Mendius 1 reaction) : l

CH 3 .CN + 2 H 2 = CH 3 .CH 2 .NH 2

Ethyl amine

l A. lai, 129.


Further, but of less importance, general reactions may be indicated
by the following equations:

CH 3 . CN + H 2 S = CH 8 . CS . NH 2


CH 3 .CO\
CH 3 . CN + CH 3 . CO . OH = >NH = Diacetamide

CH 3 .CO/
CH 3 .CO\

CH 3 . CN + >0 = N(CO . CHo) 3 = Triacetamide

CH 3 .CO/

NH 2

CH 3 .CN + NH 2 .OH =

Hydroxylamine Acetamide-oxime

CH 3 .CN



EXAMPLE : Acetic Ester from Acetic Acid and Ethyl Alcohol 1

A i-litre flask, containing a mixture of 50 c.c. of alcohol and 50
c.c. of concentrated sulphuric acid, is closed by a two-hole cork ;
through one hole passes a dropping funnel, through the other a
glass delivery tube connected with a long condenser or coil con-
denser. The mixture is heated in an oil-bath to 140 (thermome-
ter in oil) ; when this temperature is reached, a mixture of 400 c.c.
of alcohol and 400 c.c. of glacial acetic acid is gradually added
through the funnel, at the same rate at which the ethyl acetate
(acetic ester), formed in the reaction, distils over. In order to
remove the acetic acid carried over, the distillate is treated in an
open vessel with a dilute solution of sodium carbonate until the
upper layer will not redden blue litmus paper. The layers are
now separated with a dropping funnel ; the upper layer is filtered
through a dry folded filter, and shaken up with a solution of 100

i Bl. 33, 350.


grammes of calcium chloride in 100 grammes of water, in order
to remove the alcohol. 1 The two layers are again separated with
the funnel, the upper one dried with granular calcium chloride
and then distilled on the water-bath (see page 16). Boiling
point, 78. Yield, about 80-90 % of the theory.

The formation of an ester from acid and alcohol is analogous to the
formation of a salt from an acid and a metallic hydroxide :

NO 3 . H + Na . OH = NO 3 . Na + H 2 O
CH 3 . COOH + C 2 H 5 OH = CH 3 . COOC,H 5 + H 2 O

The two reactions take place quantitatively, but not in a similar
manner. A strong acid reacts almost quantitatively with an equivalent
weight of a strong base, and the product of this neutralisation is a salt.
Upon this depend the processes of acidimetry and alkalimetry. But
equimolecular quantities of an acid and an alcohol do not yield the
theoretical quantity of the ester. A maximum quantity of ester is
formed, but this falls short of the quantity required by theory, and it is
impossible, even when the reacting substances are kept in contact, to
convert the unchanged acid and alcohol into ester beyond a certain
limit. If. for example, equimolecular quantities of acetic acid and
alcohol are allowed to interact, only two-thirds of these enter into the
reaction, the maximum yield of ester being 66.7% of the theory. It is
impossible to cause a union between the remaining one-third of acetic
acid and alcohol, even when the reaction is continued for a long time.
The difference in the quantitative course of the reaction in the forma-
tion of an ester is due to the "reversibility of the reaction"; i.e. the
reaction products on the right-hand side of the equation (ester and
water) will interact in such a manner as to reverse the reaction :

CH 3 . COOC 2 H 5 + H 2 O = CH 3 . COOH + C 2 H 5 OH
In reactions of this order the two sides of the equation are united, not
by an equation sign, but, as proposed by van't Hoff, by two arrows
pointing in opposite directions :

CH 3 . COOH + C 2 H 5 OH ^> CH 3 . COOC 2 H 5 + H 2 O
The reaction in the neutralisation of a strong acid with a strong
base is, on the other hand, unlike esterification, since it is " an irre-
versible or a complete reaction " ; the water that is liberated does not
react with the salt to reverse the reaction and regenerate the acid and
the base. In reality this difference does not exist. All reactions are

1 Calcium chloride forms a compound with alcohol. (Compare page 54.)


reversible. But when a reaction product is extremely insoluble, or
when it is a gas, or when for other reasons the final products have
little tendency to react and bring about the reverse change (and this
is the case in the above example of the neutralisation of a strong acid
with a strong base), then one of the two opposing reactions is said to
be complete " within measurable limits," and it is called an u irreversible
reaction in the ordinary sense," although not in the strictest sense.
While in irreversible reactions chemical equations enable us to calculate
the amount of the products from given quantities of reacting substances,
in reversible reactions strictly quantitative stoichiometric methods
do not give the desired information. But by the aid of the highly
important Law of Mass Action (Guldberg and Waage, 1867), it is pos-
sible to determine to what extent a reversible reaction may be complete.
As has already been mentioned, when equimolecular quantities of
acetic acid and ethyl alcohol are allowed to react for some time, only
two-thirds of these substances will be transformed into acetic ester and
water. A " state of equilibrium " will finally be established, and the
reaction mixture will have the following constant composition :

| ester -f f water +^ acetic acid + i alcohol

The same equilibrium is established, if, instead of a mixture of acid
and alcohol, a similar mixture of ester and water is taken. In this case
the ester will be partially saponified into acetic acid and alcohol, but
the reaction will proceed only until of the ester is saponified. An
equilibrium will once more be established as above, so that f of ester
and water, and of acetic acid and alcohol will be obtained.

It must not be assumed that in an equilibrium of this kind the mole-
cules of the four substances remain unaltered (static equilibrium). On
the contrary, while acetic acid and alcohol are forming ester and water,
the molecules of ester and water are simultaneously reacting to bring
about the reverse change (dynamic equilibrium). In spite of this con-
tinuous reaction an equilibrium will exist, i.e. the composition of the
system will remain unaltered, when the velocities of the two opposing
reactions are the same, i.e. when in unit time an equal number of ester
molecules is formed and saponified.

The formation of ethyl acetate from acetic acid and alcohol may be
expressed by the following equation of mass action :

where C s , C A , C E , C w show the " concentration " of acetic acid, alcohol,
ester, and water respectively, and K is a constant. By concentration,


or " active mass " (Guldberg and Waage) is not meant the weight of
each substance in the total volume or in unit volume, but the relative
number of molecules, i.e. the weight of each substance divided by its
molecular weight (the number of gramme-molecules or moles). The
equation shows that when the four substances are in equilibrium with
one another, the product of the concentrations of acetic acid and alco-
hol divided by the product of the concentrations of ester and water
will be equal to a constant. How can this constant be calculated ?
We simply ascertain by analytical methods the weights of the four
substances that are in equilibrium with one another in a concrete ex-
ample, calculate the concentrations in accordance with deductions men-
tioned above, and introduce these values into the equation given.
This may be readily done in our example, since three of the substances
(alcohol, ester, and water) are neutral, and the quantity of the fourth,
the acetic acid, may be easily ascertained by titration. If we take, e.g.,
equimolecular quantities of acetic acid and alcohol, namely, 60 grammes
of acetic acid and 46 grammes of alcohol (and this will contain an
equal number of molecules), we can determine the amount of acid in
one c.c. of this mixture, at the first minute, by titration. If we now
allow the two substances to react for some time, and titrate one c.c. of
the mixture at stated intervals, the titre of the acid will be found to
diminish gradually, until finally it remains constant, due to equilibrium.
If now we compare the maximum first titre with the final minimum
titre, we shall find that the latter is exactly one-third of the former ;
i.e. at equilibrium only one-third of the original molecules of acetic
acid remain uncombined, the other two-thirds having been changed
into the ester. Since one molecule of acid yields one molecule of ester,
the number of ester molecules is exactly two-thirds of acetic acid mole-
cules used originally for the experiment. Since further, with the
formation of every ester molecule a water molecule is also formed, the
number of water molecules is also exactly two-thirds of acetic acid
molecules taken originally. And finally, since with every molecule of
acid one molecule of alcohol reacts to form the ester, two-thirds of the
alcohol molecules are used up, and only one-third remain unchanged at
equilibrium. We have thus determined the amount of all four sub-
stances at equilibrium by a mere titration. Consequently, we have the
following values in our equation :

C a = 1 1 C A = I ; Cjt = | ; C w =.
If we carry these values into the above equation, we obtain :


M 4


Thus when we have accurately determined the value of A' in a single
experiment, we shall be in a position to calculate the quantitative yield
of acetic ester at equilibrium for all proportions of acetic acid and
alcohol. Suppose we use, e.g., one gramme-molecule of acetic acid with
two gramme-molecules of alcohol, and let x be the number of gramme-
molecules of ester at equilibrium ; the gramme-molecular quantity of
water will also be represented by x. The gramme-molecular quantity
of unchanged acetic acid will then be (i x), and that of unchanged
alcohol will be (2 x). Making these substitutions in our equation,
we obtain :

(i -x). (2 -x) _ \
x.x 4

X= 2 2VJ

Since the quantity of acetic acid used is only one gramme-molecule,
x cannot be greater than one, and we are thus concerned only with the
negative sign. Thus .ris equal to 2 2>/| = 0.85, i.e. 0.85 gramme-
molecules of ester are obtained at equilibrium, i.e. 85% of the acetic
acid is transformed into ester. If, therefore, instead of using equi-
molecular quantities of acetic acid and alcohol, we double the theoreti-
cal quantity of the latter, 85 % of the acetic acid will be transformed into
ester instead of 66.7 %.

The following problems may be solved in this connection :
How much ester will be formed when one gramme-molecule of acetic
acid is treated with three gramme-molecules of alcohol ? How much
ester will be formed when 30 grammes of acetic acid and 50 grammes of
alcohol are used ? What proportions of acetic acid and alcohol must
be used in order to transform 75 % of the former into ester ?

As the above example shows, the yield of ester from the same
quantity of acetic acid is greater, the larger the amount of alcohol used.
This also follows directly from the equation of mass action given above.
As we have seen, K must have the constant value of \ for all propor-

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