Copyright
Hugh McGuigan.

An introduction to chemical pharmacology: pharmacodynamics in relation to ... online

. (page 9 of 30)
Online LibraryHugh McGuiganAn introduction to chemical pharmacology: pharmacodynamics in relation to ... → online text (page 9 of 30)
Font size
QR-code for this ebook


Friedel and Craft's Reaction for Toluene Synthesis. — When
benzene is treated with methyl chloride in the presence of alumi-
num chloride, which acts as a catalyzer, toluene is formed
according to the following reaction:



/\



-hCHaCl =



+ HC1



CHa



Toluene is also formed by the dry distillation of balsam of tolu
or by distilling toluic acid with lime

C6H4(CH3)COOH = CeHeCHg + CO2.

XI. AROMATIC ALCOHOLS, AND PHENOL ALCOHOLS

When a benzene compound contains* an hydroxyL group in a
side chain it is known as an aromatic alcohol. Thete ra^jr also
be mixed compounds in which both phenol and alcohoiicrgro^ips-
are present, e. gf.: ' ^^^ ' »

1. Benzyl alcohol or phenyl carbinol



CeHsCHaOH or



CH2OH



is a type of the aromatic alcohols; while



Digitized by VjOOQ IC



102 CHEMICAL PHABMACOLOGT

2. Saligenin or salicyl alcohol



OH



C6H4OHCH2OH or



.CH2OH



is both a phenol and an aromatic alcohol.

Benzyl alcohol has recently come into vogue as a local anes-
thetic, and benzyl benzoate has been advised in a variety of
internal conditions thought to be due to a spasmodic condition of
smooth muscle. It undoubtedly has some local action, but it
will take some time to evaluate it as a therapeutic agent. It
has the general properties of alcohols.

Saligenin. — Sal^enin is found in willow bark in the glucoside
salicin which is a combination of saligenin and glucose (p. 193).
It can be prepared synthetically by the action of formaldehyde
on phenol —



.0



+ HC



OH



\



H



CH2.OH
OH



Saligenin i^ oxidized in the body to salicylic acid. Like all
phenols ii> has anesthetic properties.

Cinnamyl alcohol, C6H5CH:CH.CH20H, is another phenol
alcohol, but it differs from benzj'^l alcohol in that the Bide chain is
unsaturated. It is a crystalline substance with the odor of
hyacinths, and is present as an ester in the resin storax. It can
also be prepared by heating benzaldehyde and sodium acetate
together, in presence of a dehydrating agent.



CeHs— CH

benzaldehyde



O + H2 CH COONa

sodium acetate
= CeH5 — CH = CH



-COONa



Digiti



zed by Google



ALDEHYDES OF THE ABOMATIC SERIES



103



It is not used as a medicine, but the aldehyde is added to per-
fumes to give the odor of cinnamon. Other aromatic ^alde-
hydes used in perfumes are:
Citral or geranial . . . which gives the odor of lemon —

(CHj) 2C :CH.CH j.CH2.C(CH,) :CH.CHO
Vanillin . . . which gives the odor of vanilla —

/CHO 1

CeH,A)CH, 3

X>H 4

Piperonal . . . which is related to vanillin and coumarin —

.CHO 1



CeH*



-O.



o



>



CH2



It possesses the odor of heliotrope to a remarkable degree. In
commerce it is known as heUotropin.

ALDEHYDES OF THE AROMATIC SERIES

Benzaldehyde is foimd in bitter almonds as the glucoside
amygdalin:

C20H27NO11 + 2H2O = eCeHijOe + HON + CeHBCHO
amygdalin glucose benzaldehyde

Benzaldehyde also occurs in ester combination with benzoic
and cinnamic acid in balsam of tolu, peru, and in storax.
Salicylic aldehyde —

Saligenin + O = Salicylic aldehyde



OH
CH2OH +



OH
C



^ + H2O
^H



The free aldehyde occurs in the essential oil of spiroea ulmaria
and in the blossoms of meadow sweet and other volatile oils.



Digiti



zed by Google



104 CHEMICAL PHARMACOLOGY

It is a fragrant colorless liquid B.P. 196® C, which is readily
oxidized to salicylic acid.



OH
COOH



In the body each of these aldehydes is oxidized to the correspond-
ing acid.

KETONES OF THE AROMATIC SERIES

The only aromatic ketone used to any extent in medicine is
aceto phenone, or hypnone or phenyl methyl ketone, C6H6CO.CH8.
It has fairly strong hypnotic properties, due to the methyl group,
but the action is more powerful and possesses no advantages
over the well known hypnotics of the aliphatic series.

Phenyl ethyl ketone, C6H5CO.C2H6, has a more powerful
action than acetophenone but less than the aliphatic series. It
also is oxidized in the body to benzoic acid.

Benzo phenone, CeHerCO.CeHs, has slight hypnotic properties,
but much less than that of the aliphatic ketones.

When fused with KOH it breaks down into benzoic acid and
benzene and we should expect this reaction to take place to some
extent in the body.

XII. ACIDS AND RELATED COMPOUNDS

Benzoic Acid. — Benzoic acid, CeHsCOOH, is readily prepared
by oxidation of benzaldehyde. It is found in gum benzoin and
in all balsams. Crystallization takes place from hot water in
glistening flat plates or needles which melt at 120^-121^0. It
reacts readily with alkali hydrates and carbonates to form benzo-
ates. Benzoic acid or the benzoates have very little toxicity.
They are not much used in medicine at the present time, having
been superseded by the salicylates.

When taken into the body, benzoic acid combines with glyco-
coU (amino acetic acid) to form hippuric acid, and is excreted as



Digiti



zed by Google



ACIDS AND RELATED COMPOUNDS 106

such C«H5C00fl + H2N.CH2COOH = CeHfiCO.HN.CHaCOOH
(hippuric acid).

Salicylic acid is the most important hydroxy benzoic acid in
materia medica. It occurs as the methyl ester in the oil of
wintergreen (oleum gaultheria) and in the oil of birch (oleum
betulae).

There are some of the free acids in these oils, and also in the
buds of spirsea ulmaria. It can be prepared by the action of
CO2 on sodium phenate at 200°C.

.OH
2C«H60Na + CO2 = CeH4<^ + CoHbOH

^COOH

Salicylic acid is a strong antiseptic and has been used in the
preservation of food, wines, beer, etc.

OH •

COONa



Sodium salicylate is a frequent remedy in the treatment of
acute rheumatism. Its derivatives, salol, and aspirin, are used
for the same purpose.

It was formerly believed that the synthetic salicylic acid
possessed toxic properties and should not be used in medicine.
Recent investigation has shown, however, that the natural and
synthetic salicylates are identical in therapeutic action. The
earlier toxic action was due to impurities.

When the carboxyl (COOH) group is introduced into the
phenol-nucleus, the action of the phenol is greatly modified,
and the toxicity lessened. The extent of the change, however,
depends on the relation of the OH and COOH in the ring. If
they are in the ortho (1:2) position, as in ordinary salicylic acid,
the antiseptic power is about the same as phenol and the anti-
pyretic action is greatly increased. The 1:3 and 1:4 oxybenzoic



Digiti



zed by Google



106



CHEMICAL PHAKMACOLOGY



acids are neither antiseptic nor antipyretic in action. Also the
introduction of a methyl group in place of the hydroxyl hydrogen



As in ortho-methoxy benzoic acid



OCH3
COOH



greatly . lessens the antiseptic and antipyretic action, just as
methoxy quinine is less antipyretic than quinine.

On the other hand, the introduction of the acetyl group,
CHsCO, as in aspirin, does not cause much change in action,
and in some respects improves the salicylate as a therapeutic
agent.

Aspirin is acetyl salicylic acid and is prepared by the action of
acetyl chloride on salicylic acid at high temperatures.



OH



+ CH3CO.CI =



COOH



OOCCH3



COOH + HCl



The stomach tolerates it better than sodium salicylate.

Salol is phenyl saUcylate. It is formed by the action of a
dehydrating agent like POCI3 on a mixture of phenol and salicylic
acid.



OH



COOIHHOi




OH
COOCeH5+H20



salicylic
^rcid



phenol



salol



Digiti



zed by Google



HESOTAN



107



It is also formed by heating salicylic acid at 200-220°C.

+ H2O + CO,



.OH .OH

2C«H4 V = CtHiv

\nf\nrf ^COOC^Hg



^COOH

Salol is used as an intestinal antiseptic, the action being due
mainly to the slow liberation of phenol, in the natural alkalinity
of the intestine. The principle of giving salol to obtain the
action of phenol and salicylic acid in the intestine without their
irritating action on the stomach was first used by Nencki and
is known as Nencki's salol principle (q.v.), p. 100.

Mesotan or the monomethyl ester of saUcylic acid is used to a
considerable extent in medicine. It is prepared by the action of
chlor methyl ether on sodium salicylate:



OH



C00\ Na



+ CH



'\



CI ) - CH2



/



o



OH

COOCHjO.
CH8+ NaCl



Sodium salicylate + Chlormethyl

ether



Mesotan



When used locally in acute rheumatism it may produce derma-
titis, probably by the irritative action of its hydrolytic products.
It readily undergoes hydrolysis as follows :



CtR






OH



/



OH



O



COOCH2O.CH8



Mesotan



-I-H2O = C,H4^ +HC+CHsOH



COOH \
H

salicylic formal- methyl
acid dehyde alcohol



Nothing definite can be stated about the form in which the sali-
cylates are excreted. It was formerly taught that salicylic acid
combines with amino acetic acid and is excreted as salicyluric
acid (c/. benzoic ^cid), Recent work doe§ not substantiate



Digiti



zed by Google



108



CHEMICAL PHARMACOLOGY



this statement. In the earlier work it is thought that the product
isolated as salicyluric from the urine was salicylic acid, mixed with
some impurities.

Cinnamic acid or phenyl acrylic acid, CeHiCH :CHCOOH, is of
interest because many balsams contain it, and it is the most
important phenyl derivative containing an unsaturated side
chain. Leucocytosis in experimental animals is caused by the
use of it, and for this reason it was used for a time in tuberculosis
with the idea of increasing phagocytosis. The clinical results
have not shown any benefit.

It may be prepared by the condensation of benzaldehyde and
acetic acid or sodium acetate on

IOH2! CH.COOH = CeH5CH.CH.COOH + H2O

c^ *



cinnamic acid



CeHs

"^H + acetic acid
benzaldehyde.

Balsams are resins or oleoresins that contain cinnamic or
benzoic acids, or both these acids. The acid or its preparations
has very few, if any, uses in medicine.

Phenyl quinoline carbonic acid (atophan) or acidum phenyl
cinchoninicum or phenyl quinoline carboxylic acid = 2 phenyl
quinoline 4 carboxylic acid, C16H11O2N,

boon




CeHs



melts at 210 c. with partial decomposition. It is insoluble in cold
water, slightly soluble in cold alcohol, hot alcohol and ether. A
saturated solution in dilute HCl gives reddish brown crystals
with platinic chloride. It is soluble in ammonia from which it is
precipitated by AgNOs or lead acetate. It is used chiefly in
gout to increase the uric acid elimination. It does not relieve
the pain and inflammation of an acute attack to the same degree
as the wine of colchicum, or the alkaloid colchicine.



Digiti



zed by Google



ANILINE BODIES

The ethyl ester of atophan



COOCsHj



109






CeHs



is known as acitrin.

Novatophan is the methyl derivative of acitrin and is the
trade name for ethyl, 6 methyl phenyl quinolin, 4 carboxylate —

COOC2H5



CfiHs



Its properties and uses are the same as phenyl cinchoninic acid.

Xin. ANILINE AND TOLUENE DERIVATIVES

AniUne is the basis of the modern antipyretics.
When concentrated HNO3 acts upon benzene, nitrobenzene
is fbrmed:

CeHe + HNO3 = C6H5.NO2 + H2O

Nitrobenzene is a pleasant smelling colorless oily liquid with
the odor of bitter almonds, often used to scent soaps, but mainly
in the manufacture of aniline. It soon darkens on exposure to
air. Its boiling point is 208°C. It has a strong poisonous action.
There are on record cases in which from 10-20 drops has caused
death. It changes the blood to a chocolate color but no meth-
emoglobin has been found, but a special absorption band between
C and D (Fihlene's nitrobenzene band) appears. Nitrobenzene
also causes paralyses of the central nervous system. It is ex-
creted as glycuronic acid in the urine. Its use in medicine is



Digiti



zed by Google



no



CHEMICAL PHARMACOLOGY



limited. When introduced into the body some of it is reduced to
para-amino phenol.

OH



/\



NH2

This compound is of interest because all of the aniUne com-
pounds or antipyretics are supposed to cause a reduction of
temperature due to the formation of this substance in the body.

Nitrobenzene on reduction with nascent hydrogen gives aniline.
This is the characteristic test (see tests for aniline, p. 112):



NO2 + 6H =



NH2 + 2H2O



Aniline is moderately toxic in its action and produces hemo-
globinuria, and an abundance of urobilin. The typic«J symp-
toms of aniline poisoning are vertigo, asthenia, gastritis,
diplopia, and sometimes exfoliative dermatitis. Since the para-
amino-phenol is less toxic, attempts have been made to use this
substance as the starting point of synthetic antipyretics, rather
than anihne. Phenacetin is the result of such research.
. Acetphenetidinum or phenacetin:

OC2H5 OC2H5



NH2
Aniline



NH2

Phenetidin



NHCOCHa

Acetphenetidin



Digiti



zed by Google



ANILINE BODIES



111



The following reactions occur in the preparation of phenacetin
OH OH



+ HNO3



+ H,0



NO2
Phenol Para-nitro-phenol

There is also some ortho nitrophenol formed which can be
separated from the para by distillation with steam :
OH ONa



II.



+ NaOH



NO2

ONa



+ H2O



NOj
OC,Hs



III.



+ CsHjI



+ NaI



NO2



OCjHs



NO,
This^is reduced with hydrogen
to phenetidin.
OC2H5



IV.



+ CHsCOOH =



+ H2O



NH2 NHCOCH,

Phenetidin Paraacetphenetidin or phenacetin.



Digit!



zed by Google



112 CHEMICAL PHARMACOLOGY

If aniline be taken internally, it is excreted in combination with
glycuronic acid as glycuronate, which will reduce Pehling's
solution. Some aniline may be formed free in the urine. Ani-
line is a weak base and some of it will distil from acid solution.
It gives the following tests:

I. Hypochlorite Test. — To an aqueous solution of aniline
add a few drops of a filtered solution of bleaching powder or
sodium hypochlorite drop by drop. A purple-violet color
changing to red is produced if aniline be present.

II. Chromic Acid Test. — To a solution of aniline in a porce-
lain dish add a few drops of concentrated sulphuric acid and a
few drops of a solution of potassium dichromate. A blue color
results.

III. Bromine Water Test. — Bromine water with aniUne
gives a flesh colored precipitate. The test is sensitive to 1 in
50,000.

IV. Phenyl Isocyanide Test. — Aniline contains the NH2
group and will give the phenyl isocyanide test.

A few drops of aniUne solutiofi with chloroform and KOH,
when heated, gives the repulsive odor of phenyl isocyanide.
Acetanilide will also give this test. When acetanilide is boiled
with KOH or alcoholic KOH it is decomposed into aniline and
potassium acetate. It will then give the tests for aniline. *

V. Ether or chloroform will extract acetanilide from acid
aqueous solution. Acetanilide will give the indo-phenol
test.

Boil acetanilide with concentrated HCl and evaporate almost
to dryness. Cool and add 5 cc. saturated aqueous carboUc acid
solution, then a few drops of hypochlorite solution. A violet-red
color is produced. Carefully add a layer of ammonium hydrate;
this will take on an indigo-blue color.

Other drugs (phenacetin) give this blue color, which is charac-
teristic of acetaniUde only when preceded by the violet-red
color. See indo-phenol reactions (Richter's Organic Chem.,
1911, vol. II, p. 173).

ACETANILIDE

Acetanilide (antifebrine) is formed when aniline is treated
with acetyl chloride or acetic anhydride.



Digiti



zed by Google



ACETANILIDE



113



+ CH,C0C1-



+ HC1



NH2



NH.COCH3



II. The usual method of preparation is by boiling a mixture
of aniline and acetic acid for some hours:

C6H5NH2 + CH3COOH = CeHjNH.CO.CH, + HgO

Acetanilide is a colorless crystalline substance which melts
at 116**C. It is hydrolyzed to its components rather readily.
This happens in the body, where aniUne is converted into para-
amino phenol, which in greater part is excreted combined with
sulphuric and glycuronic acids. Some of it is excreted as oxy-
carbanile.



^0^



OH



These changes reduce the toxicity of aniline. The antipyretic
action is thought to be due to the paramino-phenol.

Antipyrine or phenyl dimethylpyrazolon is an antipyretic of
importance. It is not an aniline derivative, but is more closely
related to phenyl hydrazine.

Hydrazine, HN2.NH2, is a strong base and extremely toxic.

Phenyl hydrazine, C6H6NH.NH2, is a compound of great
practical importance and is easily prepared by the reduction of
diazo-benzene chloride (benzene diazonium chloride) as follows :

C6H5.NH2 + HCl + HNO2 = CeH5N:N.Cl + 2H2O

Diazo benzene chloride

When this is reduced with HCl and stannous chloride

CeHfiNrN.Cl + 4H = CeH6NH.NH2HCl

phenyl hydrazine, HCl, is produced which, when treated with
NaOH, the HCl is removed as NaCl. The technic of carrying

8



Digiti



zed by Google



114



CHEMICAL PHARMACOLOGY



out any of these reactions can be obtained from any book on'
methodsin organic chemistry.

Phenyl hydrazine is a most important reagent for the identifi-
cation of aldehydes and ketones with which it readily combines
to form hydrazones and osazones. With beta-diketones and
/3-ketone esters, it forms ring compoimds containing nitrogen,
the so-called pyrazoles and pyrazolones.

Phenyl methyl pyrazolone is formed when phenylhydrazine
is heated with aceto-acetic ether, as follows:



CH,-CO



HjN



CHs- C= N.



+



\



N-C,H6



• HjC - CO - OCsHs HN— CHs-* H,C— CO^

+ H,0 -I- CfljOH
Aceto-acetic ester Phenyl Phenyl methyl

hydrazine pyrazolon

The name pyrazole comes from pyrrole, a feeble basic body
found in coal tar and in the dry distillation of bones (pyros, fire;
oleum, oil). By the introduction of N into this ring, it becomes
pyrazole.



CH CH



CHv ,CH

N
Pyrrole

CH CH



NsyCH

NH

Pyrazole



Pyrazolon is:



CH

N



NH



CHj
C = O



Digit!



zed by Google



PYBAZOLON



115



1. Phenyl 2.3 dimethyl pyrazolon, or antipyrine, is:
CH,C-=^CH



CHjN^yC = O

C,H,N
The pyrazolons or ketohydro pyrazoles are the pyrazole deriva-
tives known for the longest time and are produced by the
elimination of alcohol from the hydrazones of /3-ketonic esters.
Phenyl hydrazone aceto-acetic ester, 1.3 Phenyl methyl
pyrazolon fl-ketonic esters, are esters in which the ketone group
C = O is the fi position with reference to the COOH group.
For example, in aceto-acetic ester:

CH3.CO CH» COOC2H6
(/3) (a)
The CO is in the 8, position, and this reacts with phenyl hydra-
zine to form phenylhydrazone aceto acetic ester:
CH3.C - CH2 - COOC2H6. CH8.C = CH,







N-



-N-C<H5



N C =

\y

Hj H NC,H6

This, on loss of alcohol and water,
gives, 1:3 phenyl methyl pyrazolon. Aceto-acetic ester reacts
under some conditions as if the constitution were
CH8.C(0H) :CH.C00C,H6
This last form is known as the "enol" form (alcoholic), the
other as the "keto" form. Byusing the enol form, the formation
of phenyl dimethyl pyrazolon or antipyrine can be more simply
explained.



CH,



CH3



H^



C.-^H \ ^N.HNCHs


C - NH.HNC,H6H,0


CH ■..H.) +


CH


phenyl hydrazine


1


COOC2H5


COOCjHs


aceto acetic ester


aceto-acetic


"enol" form


hydrazone



Digiti



zed by Google



116



CHEIUCAL PHABKACOLOGT



II. On heating, this loses alcohol and gives:

CH,

II

C NB.



CH



CO-



or 1 phenyl.3 methyl pyrazolon.



-NCHs

When this is treated with methyl iodide antipyrine is fonned:
CH3C=CH CHsC^CH



HN CO + CHjI

\/
NC^5 ,
phenyl methyl pyrazolon



CH3N CO +HI

\/
NCHs
phenyl dimethyl pyrazolon



Antipyrine is classed as an artificial alkaloid and like alkaloids
it unites with acids, hence when prepared in this way it is
combined with HI. The free antipyrine is separated just as
strychnine is extracted from strychnine sulphate^ — by making
alkaline with NaOH and extracting with ether, from which it is
crystallized.

The structural formula for antipyrine is proved by the synthe-
sis from methyl phenyl hydrazine and aceto-acetic ester.

(I) CH, CH, (II) CH,

I \ I /CH,

C. ;0H Hi N - NHCHs C N - NC,H,

II ' ■ II ..^-Bt^ .

CH + = CH / / -*



COOCjH,

Aceto-acetic ester (enol)

(III) CH,.C-



CO iOC,H^/



=CH



CH,.N C =
NCeHi



Digitized by



Google



PYRAMIDON



117



Antipyrine was discovered in a search for artificial quinine.
It has none of the quinine action on the malarial organism and is
injurious to the hemoglobin, lessening its oxygen carrying power.
It is very useful in the treatment of neuralgic pains, and like
phenacetin is superior to morphine in this condition. It is
eliminated largely unchanged in the urine though some glycuron-
ate is formed.

Pyramidon is said by many to be superior in most respects
to antipyrine.

PYRAMIDON

Pyramidon-dimethylaminoantipyrine is obtained by the fol-
lowing reactions:* a solution of antipyrine hydrochloride is acted
on by nitrous acid, the result being nitroso antipyrine.
CHs CH3



c—

II

CH



N.CH,



N.CHs



= + HNO» =



NO-C



+ H2O



CO— N.CJls CO— N.CeH,

When this is reduced, amino antipyrine results:

CHj



-N.CHa



NHj-C



CO— N.CJls
This is isolated by means of its benzylidene derivative, and
when it is methylated by treatment with methyl iodide it gives
pyramidon.

CH3



C-

II
(CHj),N.C



N.CH,



CO— N



CtHs



Digit!



zed by Google



118 CHEMICAL PHARMACOLOGY

Pyramidon is a solid, forming in small colorless crystals,
melting at 108°C. It is easily soluble in alcohol, ether and
benzene It is soluble in 11 parts of water. A aqueous solu-
tion saturated at 70''C deposits oily globules of the drug when
it reaches the boiling point. Its aqueous solution gives a slight
alkaline reaction.

Pyramidon is a more powerful base than antipyrine and in
therapeutics the dose required is only one-third the amount of
antipyrine that would be given. This drug has been used both
as an antipyretic and an analgesic, but the latter is the more
important use. Pyramidon may be prescribed in heart disease
and nephritis, as it affects the circulation only slightly. It is not
irritating to the stomach and does not affect the heart, blood, or
kidneys. It is claimed by some that pyramidon increases
nitrogenous metabolism, contrary to most antipyrine derivatives,
and hence should never be prescribed for diabetics. It is useful,
however, in the chronic fevers of tuberculosis, the acute febrile
conditions associated with typhoid fever, erysipelas, and pneu-
monia. In the treatment of all infectious fevers it should be '
used with care, as should all other antipyretics.

The dosage is usually from 0.3 to 0.4 gm. (5 to 6 grains)
in tablet form. A single dose is sufficient for twenty-four
hours.

Pyramidon is excreted in the urine, partly unchanged, partly
combined with glycuronic acid and some as uramino-antipyrine,
a combination of urea and antipyrine:

CHa

I

C— N.CHa

NH2.CO.NH— C

CO-N.CeHj

Another derivative, rubazonic acid, C20H17N6O2, occurs in the
urine after standing, and produces a red color due to oxidation.
Its behavior recalls purpuric acid which is formed when uric acid
bases and caffeine are oxidized (murexide test).



Digiti



zed by Google



TESTS 119

The tests for pyramidon are:
1. Its melting point lOS^'C.

2 Solubility — soluble in 11 parts of cold water, readily soluble
in alcohol and ether.

3. Ferric chloride colors the neutral or slightly acidulated
solution a blue violet color.

4. Fuming nitric acid colors pyramidon solutions blue violet.

5. Bromine water gives a gray color to pyramidon solutions.

6. Tincture of iodine colors aqueous solutions of pyramidon
blue.

Acetanilide Tests

1. It melts at 112M14''C. It is soluble in 190 parts of water,
4 of alcohol and 17 of ether. '

2. It gives the phenol isocyanide test as follows: Add 6 cc. 5
per cent. KOH and heat. It gives the odor of aniline. Now
add 1 cc. chloroform and again heat. The odor of the isocyanide
is produced (see p. .43).

3. Bromine water gives a white precipitate with an aqueous
solution of acetanilide.

4. Heated with a little hydrochloric acid, and an equal volume
of 5 per cent, phenol added, and then if an equal volume of filtered
saturated solution of chlorinated lime be added, it acquires a
brownish red color, which becomes a deep blue on the addition
of excess of NH4OH.

5. When boiled with KOH as in test 2, aniline is liberated.
This may be extracted with ether. If, after evaporation of the
ether, a few drops of calcium or sodium hypochlorite be added
a violet or purple color changing to dirty red indicates aniline.



Online LibraryHugh McGuiganAn introduction to chemical pharmacology: pharmacodynamics in relation to ... → online text (page 9 of 30)