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GIFT OF




ORGANIC CHEMISTRY

INCLUDING CERTAIN PORTIONS OF

PHYSICAL CHEMISTRY



FOR



MEDICAL, PHARMACEUTICAL, AND BIOLOGICAL
STUDENTS

(WITH PRACTICAL EXERCISES)



BY



HOWARD D. HASKINS, A.B., M.D.

Professor of Biochemistry, Medical Department, University of Oregon

Formerly Associate Professor of Organic Chemistry and Biochemistry,

Medical Department, Western Reserve University



THIRD EDITION, THOROUGHLY REVISED

TOTAL ISSUE, FIVE THOUSAND



NEW YORK

JOHN WILEY & SONS, INC.

LONDON: CHAPMAN & HALL, LIMITED

1917




COPYRIGHT, 1907, BY
H. D. HASKINS

AND

J. J. R. MACLEOD



COPYRIGHT, 1917, BY
t\ HOWARD D. HASKINS



PRESS OP

BRAUNWORTH & CO.

BOOK MANUFACTURERS

BROOKLYN. N. Y.



PREFACE TO .THIRD EDITION



IN this edition the subject matter has been
rearranged to a considerable extent. Numerous
revisions have been made.

The discussion of the physical chemistry topics
has been amplified, and, hi some cases, partly re-
written (e.g., osmotic pressure and colloids).

It will gratify the author greatly to receive for
consideration suggestions and criticisms from any
who are using this text-book.

HOWARD D. HASKINS.

PORTLAND, OREGON.
Nov. 1, 1916.

iii



380850



PREFACE TO SECOND EDITION



THE author has endeavored to revise the entire
book, striving to make it more reliable as a reference
book, and more complete from the standpoint of the
student of medical sciences. It is our belief that an
organic chemistry text-book for the use of medical
students should give the chemistry of all the organic
compounds (of any importance) that enter into the
study of physiology, biochemistry, and pharma-
cology.

H. D. HASKINS.

July 1, 1912.

iy



PREFACE TO FIRST EDITION



AMONG the most important of the recent advances
in medical science are those relating to the chemistry
of the various organic substances which enter into
the composition of animal tissues and fluids, and to
the physico-chemical laws which govern, or at least
influence, many physiological processes. The dis-
covery of the chemical constitution of the purin
bodies, of many of the urinary constituents, and of
sugars and fats, as well as the new theories of solu-
tion and catalysis, has revolutionized the teaching
of biological and clinical chemistry; and in phar-
macology and pharmacy a knowledge of organic
and physical chemistry is almost essential. The
study of these parts of chemistry is, therefore, daily
coming to be of greater importance to the medical
student and is already included in the curriculum
of the best medical schools. 1

As taught in the regular college classes in organic
chemistry, the subject certainly absorbs too great a
proportion of the medical student's time, and much
is included in the course which has no bearing on

1 The recent application by Arrhenius of certain physicochemical
laws in explaining the mode of action of antitoxins, etc., is an
illustration of the increasing importance of a knowledge of physical
chemistry for the medical student.



Vi PREFACE

his future work, and much is omitted which is of
immense importance to him.

It was with the idea of presenting in the simplest
manner the facts of organic and physical chemistry
which have an essential bearing on medical science
that the present book was written. For the sake of
simplicity, the subject-matter is arranged in a some-
what different manner from that usually followed in
text-books for chemical students. In the first por-
tion of the book considerable attention is given to a
description of the methods employed for purifying
and testing the purity of substances preparatory
to their further investigation. It is to this part
of his work that the investigator in bio-chemistry
has to give his closest attention and in which he
often meets with the greatest difficulties. A chap-
ter giving a fairly full description of the methods of
elementary analysis follows, and then a chapter on
the principles of physical chemistry as applied to
molecular weight determinations and to the theories
of osmosis, solution, etc. Those facts of physical
chemistry which it is desirable to call attention
to that are not included in this chapter are inserted
where they can most conveniently be studied along
with the organic compounds. The remainder of
the book includes a description of the various groups
of organic substances, and, where possible, there is
chosen, as the representative of each group, some
body of medical or biological importance. Numer-
ous practical exercises accompany the text, and these
have been chosen and arranged so as to occupy about
four hours of laboratory work per week for a thirty-



PREFACE vii

week session. A few more advanced exercises are
given for the sake of completeness, and it is left
to the teacher whether or not he shall have them
performed by the student. The cyclic compounds
and the more complicated of the benzene deriva-
tives may also be omitted at the discretion of the
teacher.

In the Appendix will be found a schedule showing
how the work of the class in our own institution is
arranged so that all the members of it may do those
experiments involving the use of expensive apparatus.
The laboratory work is required of our students. We
believe that by conducting an elementary analysis
and by doing cryoscopic experiments with Beck-
mann's apparatus, as also preparing pure organic
compounds, the student acquires an idea of accuracy
and an insight into the principles of chemical methods
which he cannot otherwise obtain, and which,
without any doubt, will be of immense value to him
in all his future work. Our experience is, also,
that students of whom laboratory work is required
get a grasp and understanding of the subject of
organic chemistry such as others rarely acquire.

H. D. HASKINS.

J. J. R. MACLEOD.

April, 1907.



CONTENTS



CHAPTER I.

PAGE

THE NATURE AND COMPOSITION OP ORGANIC COMPOUNDS ... 1



CHAPTER II.
PURIFICATION AND IDENTIFICATION OF SUBSTANCES 7

CHAPTER III.
ELEMENTARY ANALYSIS 28

CHAPTER IV.

MOLECULAR WEIGHT DETERMINATION. THE NATURE OF SOLU-
TIONS. OSMOTIC PRESSURE. IONIZATION. SURF ACE TEN-
SION. VISCOSITY. COLLOIDAL SOLUTIONS 40



CHAPTER V.

FORMULAE, EMPIRICAL AND STRUCTURAL. ISOMERISM 98

SYNOPSIS OF CHAPTERS I-V 100

CHAPTER VI.

PRELIMINARY SURVEY OF ORGANIC CHEMISTRY 101

SYNOPSIS OF FATTY COMPOUNDS 115

CHAPTER VII.

SATURATED HYDROCARBONS. METHANE SERIES 117

ix



X CONTENTS

CHAPTER VIII.

PAGE

HALOGEN SUBSTITUTION PRODUCTS OF THE PARAFFINS 124

CHAPTER IX.
ETHERS 132

CHAPTER X.
PRIMARY ALCOHOLS : . , 136

CHAPTER XI.
ALDEHYDES 146

CHAPTER XII.

FATTY ACIDS AND ETHEREAL SALTS. FURTHER OBSERVATIONS

IN PHYSICAL CHEMISTRY 157

CHAPTER XIII.

SECONDARY AND CERTAIN OTHER MONACID ALCOHOLS.

KETONES 189

CHAPTER XIV.
DIACID ALCOHOLS AND DIBASIC ACIDS 193

CHAPTER XV.

\
TRIACID ALCOHOLS, FATS, AND SOAPS 199

CHAPTER XVI.
HYDROXY-ACIDS 212

CHAPTER XVII.
CARBOHYDRATES AND GLUCOSIDES 227

CHAPTER XVIII.

NITROGEN DERIVATIVES. (ALSO PHOSPHORUS AND ARSENIC
COMPOUNDS.) 255



CONTENTS xi

CHAPTER XIX.

PAGE

AMINO ACIDS AND ACID AMIDES 266

CHAPTER XX.

ACID IMIDES. COMPLEX AMINO AND IMIDO COMPOUNDS,

INCLUDING POLYPEPTIDES 284

CHAPTER XXI.

UNSATURATED HYDROCARBONS AND THEIR DERIVATIVES 299

CHAPTER XXII.

SULPHUR DERIVATIVES 306

CHAPTER XXIII.
CYCLIC AND BI-CYCLIC COMPOUNDS 309

CHAPTER XXIV.
THE AROMATIC HYDROCARBONS 316

CHAPTER XXV.

AROMATIC HALOGEN DERIVATIVES 333

CHAPTER XXVI.
AROMATIC HYDROXY COMPOUNDS 336

CHAPTER XXVII.
AROMATIC ACIDS 356

CHAPTER XXVIII.
AROMATIC NITROGEN DERIVATIVES. . . 374



xii CONTENTS

CHAPTER XXIX.

PAGE

SULPHUR AND ARSENIC DERIVATIVES 391

CHAPTER XXX.
QUINONES, DYES AND INDICATORS 398

CHAPTER XXXI.
AROMATIC COMPOUNDS HAVING CONDENSED RINGS 409

CHAPTER XXXII.

HETEROCYCLIC COMPOUNDS 414

SYNOPSIS OF AROMATIC COMPOUNDS 423

CHAPTER XXXIII.
ALKALOIDS AND DRUG PRINCIPLES 425

APPENDIX.

NOTE TO THE INSTRUCTOR 443

REFERENCE TABLES

I. Specific Gravity and Percentage of Alcohol 445

II. Weight of Pure Gas in 1 c.c. of Moist Nitrogen at

Various Temperatures and under Various Pressures . . 447

III. Specific Gravity and Percentage of NaOH in Aqueous

Solution 448

IV. Specific Gravity and Percentage of KOH in Aqueous

Solution 449

V. Acetic Acid, Specific Gravity and Freezing-point at

Various Concentrations 450

VI. Vapor Tension of Water and of 40% KOH at Various

Temperatures 450

VII. Dissociation Constants of Certain Organic Acids 451

VIII. Dissociation Constants of Certain Bases 451

IX. Power of Certain Acids to Cause Hydrolysis 452



CONTENTS xiii

ILLUSTRATIONS.

PAGE

FIG. 1. Melting-point Apparatus 10

2. Sublimation Apparatus after Gattermann 14

3. Fractional Distillation Apparatus after Gattermann. 15

4. Fractionating Column after Gattermann 15

5. Steam Distillation Apparatus after Gattermann .... 16

6. Vacuum Distillation Apparatus after Gattermann. . . 17

7. Boiling-point Flask 18

8. Picnometer 23

9. Westphal's balance 23

10. Hydrometer 24

11. Combustion furnace 30

12. Calcium Chloride and Potash Absorption Apparatus
after Gattermann 31

13. Mixing Tube 32

14. Nitrogen Burette after Gattermann 37

15. Victor Meyer's Vapor Density Apparatus after
Walker 45

16. Pfeffer's Osmotic Pressure Apparatus 49

17. Beckmann's Apparatus and Thermometer after
Walker 61

18. Flashing-point Apparatus after Remsen 122

19. Ethyl Bromide Apparatus after Gattermann 126

20. Aldehyde Apparatus after Fischer 152

21. Acetyl Chloride Apparatus after Gattermann 167

22. Tartaric Acid Models, Illustrating Stereoisomerism . . . 223

23. Sodium Ammonium Racemate Crystals after Holle-
man 224

24. Ethylene Bromide Apparatus after Gattermann 301

25. Collie's Benzene Model .324



ORGANIC CHEMISTRY



CHAPTER I

THE NATURE AND COMPOSITION OF ORGANIC
COMPOUNDS

Definition of Organic Chemistry. The various inor-
ganic chemical compounds are classified by the chem-
ist into groups, a group comprising all the com-
pounds of some particular element. Thus we
have the iron group, the sulphur group, and so on.
On account, however, of the great number 1 of
compounds containing the element carbon, the group
of carbon compounds is set apart for consideration
as a special branch of chemistry. Organic chem-
istry is that branch: it is the chemistry of carbon
compounds. This definition is, however, not strictly
accurate, for it is customary to treat of the oxides
of carbon and the carbonates in inorganic chemistry.

The name organic owes its 'origin to the old-time
belief that these compounds of carbon could be pro-
duced only by the agency of vegetable or animal
organisms, by so-called vital activity. That such a
notion is untenable was first shown by Wohler,
who, in 1828, obtained urea the main organic
1 About 150,000.



CHEMISTRY



constituent of urine by simply evaporating an
aqueous solution of ammonium iso-cyanate, his
intent being to recrystallize the latter salt (p. 278).
Since that date thousands of organic compounds
have been prepared in the laboratory without
any assistance from vital processes. In fact, a great
proportion of the compounds known to organic
chemists have never been discovered in nature,
but have been created in the chemical laboratory.

Elements and Their Detection. In organic com-
pounds carbon may exist in combination with one,
two, three, four, or even five other elements. The
most important elements present in organic com-
pounds, together with their atomic weights and
valences, are as follows:

Carbon C, atomic wt. 12, valence IV.
Hydrogen, H, " " i, " I.
Oxygen, O, " "16, " II.
Nitrogen, N, " "14, " III and V.
Phosphorus,?, " "31, " III and V.
Sulphur, S, " "32, " II, IV and VI.

Some important compounds contain the halogens
(Cl, Br, I). The presence of most of these elements
in organic compounds can be quite readily detected
by simple tests, the principal ones being incorporated
in the experiments that follow. The presence of
oxygen cannot be directly determined; it is detected
by rinding the percentage composition of the com-
pound and observing that the sum of the per cents
of all the other elements is less than one hundred.



ORGANIC COMPOUNDS 3

EXPERIMENTS. Detection of carbon, hydrogen,
nitrogen, sulphur, phosphorus and chlorine.

(1) C and H. Dry a clean test-tube in the gas-
flame. Fit it with a cork through which passes
a glass tube bent at a right angle. Mix in a mortar
a little dry cane sugar and ten times as much dry
CuO, pour this mixture into the test-tube, cork, and
dip the outside end of the glass tube into baryta
solution contained in another test-tube. Heat the
sugar mixture over a flame. Drops of water con-
dense on the cool parts, showing the presence of H. 1
Cloudiness in the baryta is due to carbon dioxide,
BaCOs having been formed, and indicates the
presence of C. By heating, CuO is reduced; its
oxygen combines with the C and the H of the organic
substance to produce CO2 and EbO.

(2) N and S. (a) Triturate in a mortar some dry
albumin with twenty times as much soda-lime, 2
transfer the mixture to a test-tube, and heat over
a flame. Test the vapor that appears for ammonia,
the presence of which proves the existence of N in
the compound examined.

(6) Put into a dried test-tube some dry albumin
equal in bulk to a bean. Add a small piece of clean
metallic sodium. Heat until the mass is red-hot,
then gently drop the test-tube into a mortar contain-
ing 10 c.c. of distilled water. The tube breaks,
and NaCN and Na 2 S go into solution. Grind

1 Water of crystallization must be removed before testing
for hydrogen.

2 Soda-lime is made by gradually adding powdered quick-
lime to a saturated solution of caustic soda with constant stirring.



4 ORGANIC CHEMISTRY

up the charred mass with the pestle. Filter and
divide the filtrate into portions A, B, C, and D.
To A add NaOH until strongly alkaline, then a few
drops of freshly made FeSO* solution l and a drop
of FeCls solution. Boil this mixture two minutes,
cool, and acidify with HC1. The appearance of a
greenish-blue color or a precipitate of Prussian
blue indicates N. To B add a few drops of a fresh
solution of sodium nitroprusside; 2 a reddish-violet
color points to the presence of S. To C add lead
acetate solution and acidify with acetic acid. A
brownish-black discoloration or precipitate is due
to S. Neutralize D with HC1; add a few drops of
FeCls solution; a red color, which is removed by
HgCb, is caused by the presence of sulphocyanide.

If sulphocyanide is not formed in examining an organic
compound by this method (it is not formed if a sufficient excess
of sodium is used), halogens may be tested for in the filtrate
by boiling some of it with one-tenth volume of concentrated
HN0 3 (HCN or H 2 S driven off, prolonged boiling may be
necessary to remove all the HCN) and then testing with
AgN0 3 (precipitate of AgCl, AgBr, or Agl). In this test
iodine and bromine are set free by the nitric acid and can be
detected by conducting the vapor into a test-tube containing a
little CS 2 (for this test heat the mixture in a short test-tube
and close the tube with a stopper having a bent tube as in
exp. 1).

If it is desired to detect N, S, or halogens in a liquid it is
best to drop the liquid on melted sodium contained in a test-
tube that is held vertically by being thrust through a hole in
an asbestos pad.

1 Sodium ferrocya'nide is formed by this treatment.
Formula =Na 2 Fe(CN) 6 (NO).



ORGANIC COMPOUNDS 5

(3) Cl. Put a little pure powdered soda-lime
in a dry test-tube, add as much chloroform as it
will soak up, and heat strongly. Break the tube
and powder the mass in a mortar. Treat with
strong HNOs until dissolved. Test with AgNOs.
A control test with soda-lime alone should give
only a slight turbidity.

(4) P. Mix some dry nucleoprotein (or dry yeast)
with twenty parts of fusion mixture (1 part Na2COs
+2 parts KNOs). Heat in a crucible until the mass
is almost white. When cool, dissolve it in a little
hot water and pour the resulting solution into an
evaporating dish. Add HC1 until neutral and filter.
To half of the filtrate add NH 4 OH until strongly
alkaline, then add magnesia mixture. 1 The phos-
phates, formed by the oxidation of the phosphorus
of the compound, cause a white precipitate. To
the other half of the filtrate add HNOs until strongly
acid, then add an equal volume of ammonium
molybdate solution 2 and heat in a water bath until
a fine yellow precipitate appears.

Having thus determined what elements are pres-
ent in the organic compound that he is investigating,
the chemist next proceeds to its more thorough

1 Magnesia mixture is made as follows: Dissolve 55 gm.
of pure MgCl 2 crystals and 70 gm. NH 4 C1 in 1300 c.c. of water
and add 350 c.c. of 8% ammonium hydroxide.

2 Ammonium molybdate solution is made as follows: Dis-
solve 75 gm. of powdered ammonium molybdate in 250 c.c. of
water with the aid of heat, and add (when cool) 35 c.c. of
C.P. NH 4 OH. Pour this into a mixture of 300 c.c. of C.P.
HN0 3 and 675 c.c. of water while stirring vigorously.



6 ORGANIC CHEMISTRY

examination. He first estimates the percentage
amounts of the various elements contained in the
substance, and then he determines its molecular
weight. He is able from these data to calculate
the empirical l formula. But more than one sub-
stance may have this same formula; therefore he
studies the reactions of the compound when treated
with reagents in order to get a clue as to how its
molecule is built up, that is, how its atoms are
linked together. And, finally, by causing simpler
substances, the structure of the molecules of which
is known, to become united (synthesis), he endeavors
to produce a substance having the same molecular
structure as his compound. If his synthetic com-
pound shows properties that are identical with the
substance under examination, the chemist then
considers that he has established with absolute
certainty the chemical construction of the com-
pound.

But all this work will end in failure unless the sub-
stance under examination be absolutely pure, i.e.,
free from admixture of any other substances. It
is necessary for us at this stage, therefore, to explain
the chief methods of purification as well as the
tests by which the purity of the substance is ascer-
tained. This will be done in the chapter that follows.

1 The empirical formula gives merely the total number of
atoms of each element in one molecule, as C*Hi 2 (see
p. 98).



CHAPTER II

PURIFICATION AND IDENTIFICATION OF
SUBSTANCES

PURIFICATION OF SUBSTANCES

THE main methods of separating an organic sub-
stance in a pure state are crystallization, sublimation,
distillation, extraction and dialysis.

Crystallization. The basis of this method is the
fact that different substances are not usually solu-
ble to an equal extent in the same solvent. For
example, acetanilide can be separated from dex-
trose by dissolving the mixture of these two in hot
water; when the resulting solution is cooled, the
acetanilide crystallizes out because of its slight
solubility in cold water, while the dextrose remains
in solution. By repeated crystallization in this
manner perfectly pure acetanilide can be obtained
(see exp. below).

Inasmuch as crystallization as a method for
separation and purification of organic compounds
is invaluable, it will be well to detail specific direc-
tions for carrying it out. (1) Carefully select a
suitable solvent. Put small quantities of the sub-
stance to be purified into several test-tubes; and
add to each a different solvent (those most commonly
used are water, alcohol, ether, chloroform, benzol,

7



8 ORGANIC CHEMISTRY

petroleum ether, acetone, and glacial acetic acid).
Discard those that dissolve the substance readily.
Heat each of the remaining. Choose the solvent
which when hot dissolves the substance readily, but
deposits crystals on cooling. The solvent should
either hold the impurity in solution when cold or
exert no solvent action on it whatever.

(2) Completely saturate at boiling temperature
a certain quantity of the chosen solvent with the sub-
stance.

(3) Filter the hot liquid through a plaited filter,
using a funnel with a short stem. (With a long-
stemmed funnel crystals may separate out in the
stem and block it.) Heating the funnel in hot
water before filtration may be resorted to.

(4) Collect the filtrate in a beaker having a
capacity twice the volume of the liquid. With
too small a beaker creeping of crystals and liquid
may occur.

(5) Cool slowly. 1 If crystals are deposited very
quickly, redissolve with the aid of heat, and pre-
vent rapid cooling by wrapping the beaker with a
towel.

(6) Cover the beaker with a piece of filter-paper
to prevent condensation-drops from falling back
into the liquid and disturbing the crystallization.
A watch-glass or glass plate completes the covering.

(7) Do not disturb the beaker until crystals have
formed. If their appearance is greatly delayed they
may often be induced to form by scratching the inner

1 5, 6, and 7 may be disregarded except when the form of the
crystals is to be studied.



PURIFICATION OF SUBSTANCES 9

wall of the beaker with a glass rod, or by " sowing "
a crystal of the substance into the liquid.

(8) If the substance is not sufficiently insoluble
in the cold solvent, crystallization may be brought
about by slow evaporation in a loosely covered
crystallization dish.

(9) Collect the crystals on a suction-filter (reject
the crystals that have crept above the surface of the
liquid), and wash them with a little of the pure
cold solvent.

(10) Dry the crystals in a desiccator, except when
they contain water of crystallization.

EXPERIMENT. Put 20 c.c. of distilled water into
a beaker and heat to boiling on an asbestos pad.
Completely saturate it with the mixture of dextrose
and acetanilide which is furnished. Filter while
hot, and cool rapidly. When a good crop of crystals
has formed, separate them by filtration. Dissolve
in a little water and recrystallize. Repeat the proc-
ess until the filtrate from the crystals no longer
gives reduction when boiled with Fehling's solution. 1
At least three crystallizations should be carried
through. Save the pure white crystals. After
they are dried in a desiccator a determination of
the melting-point may be made (see below)..

1 Fehling's reagent consists of an alkaline solution of cupric
hydroxide, the latter being held in solution by means of Rochelle
salt. The reagent should be freshly prepared by mixing equal
volumes of 7% CuS0 4 and of an alkali solution containing
25 gm. KOH and 35 gm. Rochelle salt in 100 c.c. The reagent
is of a deep-blue color, and when it is boiled with even a trace
of dextrose a red precipitate forms in it.



10 ORGANIC CHEMISTRY

To test the purity of the crystals their melting-
point is determined. The method of making a
melting-point determination will be described in
the experiments that follow. Pure crystals melt
quite sharply and completely, i.e., they become
completely melted within 0.5 to 1. The crystals
may be considered pure when, after repeated crystal-
lization (preferably from different solvents), the
melting-point remains constant for several successive
determinations. A bath of water may be used for
substances having a low melting-point (below 80 l ).
Sulphuric acid is used for higher tem-
peratures (up to 280). For still higher
temperatures paraffin is used. The
thermometer should be one with the
scale engraved on the stem. The crys-
tals should be powdered and thoroughly
dried in a desiccator.




EXPERIMENT. Make melting-point
tubes by heating a glass tube of 10 mm.
diameter in a flame until
a 2-cm. section is red,
then drawing it out. A
capillary tube about 1
mm. in diameter and 5
FlG - * or 6 feet long, is thus

obtained. Break into lengths of 6-8 cm. and seal
one end of each. Put into such a tube some
powdered chloral hydrate that has been dried
in a desiccator. Gentle scratching with a file
1 All temperatures given in this book are centigrade.



PURIFICATION OF SUBSTANCES 11

will cause the particles to travel to the bottom
of the tube. Attach the tube to a thermometer
by means of a narrow rubber band cut off from
rubber tubing, adjusting it so that the main part
of the chloral will be opposite the middle of the
bulb of the thermometer. Suspend the ther-
mometer in a beaker of water so that the bulb is
fully immersed. Heat the water very gradually.



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