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               Synthesis of 2-methyl-4-selenoquinazolone,
                    2-phenylbenzoselenazole, and Its
                              Derivatives.

                              DISSERTATION

          SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS
                      FOR THE DEGREE OF DOCTOR OF
                   PHILOSOPHY IN THE FACULTY OF PURE
                     SCIENCE OF COLUMBIA UNIVERSITY

                                   BY

                          YÜ-GWAN CHEN, M. A.

                             NEW YORK CITY

                                  1922

ACKNOWLEDGMENT AND DEDICATION

The following research was undertaken at the suggestion of Professor
Marston Taylor Bogert to whose interest and advice this work owes
whatever merit it may possess.

                                                             Y. G. CHEN.

CONTENTS

 Acknowledgment and Dedication                   2

 Abstract of the Dissertation                    4

 Purpose of the Research                         5

 Introduction                                    7

 Pharmacological Review                          8

 Tinctorial Review                              14

 Experimental:                                  16

    2-methyl-4-selenoquinazolone
        Four Methods of Preparation

    Analysis of Selenium Organic Compounds

    2-phenylbenzoselenazole
        Mononitro Derivative
        Monoamino Derivative
        Monoacetyl Derivative
        Monobenzylidene Derivative
        An Azo Dye
        Dinitro Derivative
        Diamino Derivative
        Diacetyl and Dibenzylidene Derivatives

    Dyeing with Azo Dyes

 Bibliography                                   25

 Vita                                           28

ABSTRACT OF THE DISSERTATION

1. What was attempted?

Attempt was made to study organic selenium compounds of the heterocyclic
series in reference to those properties leading to tinctorial and
pharmaceutical possibilities.

2. What were the methods of attack?

(a) Organic selenium compounds were reviewed and their properties
examined critically with those of allied compounds.

(b) Some new heterocyclic compounds of selenium were studied and their
characteristic properties more closely examined along the desired line.

3. In how far were the attempts successful?

The literature was reviewed and classified with reference to the
properties under consideration, and new selenium organic compounds were
prepared and studied which it is hoped may throw some additional light
upon the problem.

4. What contribution actually new to the science of chemistry has been
made?

(a) Compounds newly made have been shown to exhibit a distinct
tinctorial value in comparison with their analogues.

(b) They have been shown to be chemically easier to handle than the
corresponding sulphur compounds.

(c) Selenium, in the nucleus of cyclic compounds, has been shown to be
instrumental for a positive coloration at least equal to the --NH-- or
--S-- groupings. The selenocarbonyl, :C:Se, has been shown to be a more
powerful chromophore than thiocarbonyl, :C:S, or carbonyl itself, :C:O.

(d) Two series of azo dyes of selenium have been prepared and have been
shown to possess a marked tinctorial value.

(e) The following new compounds have been prepared:

    2-methyl-4-selenoquinazolone
    2-phenylbenzoselenazole[A]
    6-nitro-2-phenylbenzoselenazole
    6-amino-2-phenylbenzoselenazole
    6-acetylamino-2-phenylbenzoselenazole
    6-benzylideneamino-2-phenylbenzoselenazole
    (B-naphthyl)-6-azo-(2-phenylbenzoselenazole)
    Dinitro-2-phenylbenzoselenazole
    Diamino-2-phenylbenzoselenazole
    Diacetyldiamino-2-phenylbenzoselenazole
    Dibenzylidenediamino-2-phenylbenzoselenazole

PURPOSE OF THE RESEARCH

Since Berzelius published the first resume of the chemistry of
selenium, in 1818(1), many articles have appeared in this field.
Several reviews(2) of its compounds, including references, have been
published, besides the resumes in the chemical dictionaries. These
reviews are confined mainly to the inorganic side. No attempt has ever
been made to compile a bibliography of selenium organic compounds.

From time to time, articles have appeared, but the field is still a
promising one, with many alluring possibilities.

In the perusal of the organic records of the metal, distributed over
the span of a century, there are indications of the value of selenium
compounds for pharmaceutical and tinctorial uses. An effort has been
made to collect these scattered data for critical examination with
other analogues and sulphur compounds in particular, and to prepare and
study some new organic compounds containing selenium, for the purpose
of gaining additional light upon the chemistry of such substances, and
in the hope of discovering some which may be of practical service in
medicine or elsewhere.

Synthesis of 2-methyl-4-selenoquinalozone, 2-phenylbenzoselenazole and
Its Derivatives

INTRODUCTION

The general conception of selenium is that it is a comparatively rare
element. Few realize that it has been known for over a century and
that over twenty selenium minerals, containing from one to sixty-six
per cent. of the metal, are considered by the mining corporations as
important. Beside being a by-product of sulphuric acid manufacture, it
is separated also in the electrolytic refining of copper. The demand
for the metal is so small that there are half a dozen concerns in the
United States either willing to supply gratis any reasonable quantity
for research work, or to sell it at cost. In a special report of the
National Research Council on selenium(3), it is estimated that there
could be produced annually, without making any material additions to
the present plants, not less than 300,000 pounds.

In fact selenium has, in recent years, gradually been brought more and
more to the attention of the general public through its application to
military uses and other purposes. In the glass industry, for example,
it was used as decolorizer during the War period. It has been found
that it imparts a violet red tint to the pyrex tubing after the latter
has been used for a few combustions. The coloration is especially
noticeable when a broken piece is examined. This may find an important
place in the ceramic industry. In turning off the gas light of the city
at day break, in controlling the draft of the factory chimneys, and
in regulating the rapidity of the manufacture of sulphuric acid, the
selenium cell is an important labor saving factor. In a similar way
it is used in automatically lighting and extinguishing light buoys.
It also finds application in photometry, wireless telephony, military
telegraphy, and army signaling as well as for the transmission of
signatures, handwritings, finger prints, and images in general(3)(4).

The question of the vulcanization of rubber also should be considered.
Some experiments have been published claiming the similarity of the
action of selenium and sulphur on rubber(4)(5). The cost need not be
prohibitive, since the supply could be easily increased and the price
reduced provided there were a demand. In the personal experience of
the writer, when working with the hydrogen selenide gas, the rubber
connections of the apparatus soon turned red, and after a few hours
were so clear a red that visitors to the laboratory imagined that the
writer was using the ordinary red rubber connections. The rubber thus
changed seems to be softer and more elastic than the original; this
observation will be followed up.

In this country the National Research Council has created a special
committee of seven to investigate the various possible uses of selenium
and tellurium.

PHARMACOLOGICAL REVIEW

Duhamel and Rebiere(6)(7) showed that an injection of a trace of red
colloidal selenium into rabbits increased urea excretion regularly. In
other cases satisfactory results were claimed and the liver showed some
lesions. The histological modifications produced by injections into
rabbits are most apparent in the liver and kidneys. In the distribution
of colloidal preparations in the animal body by injection, Duhamel and
Juillard(8) found that the liver contained the greatest amount. Six
years later the former(9) used a similar preparation introduced into
the animal intravenously, and selenium was again found in the liver,
although in smaller quantity.

Sulphur compounds have similar physiological action. It is known that
triphenylstibine sulphide, or sulphoform, (C₆H₅)₃SbS, has a curative
effect in skin diseases, as it liberates “nascent” sulphur on the
skin. It is equally natural to expect some organic selenium compound
which liberates finely divided selenium to exert a remedial influence
on animal bodies. The selenoquinazolone prepared in the course of this
research and described more fully in another section of the paper, has
this prospect. The quinazolone has the following structure:

      N
  /\ / \\
 |  |   C-CH₃
 |  |   |
 |  |   NH
  \/ \ /
      C
      Se

Experiments were carried on at L’Institut Pasteur in Paris under the
supervision of M. Borel for the treatment of cancer in mice. No human
subjects were experimented upon, although results were claimed by using
selenides and their oxidized salts.

Selenium dyes were found to be medicinals, although no relation has yet
been established between constitution of these organic dyes and their
therapeutic value. Wassermann(10) made several eosin preparations,
by coupling the sodium derivative with potassium selenocyanide. The
red dyestuff thus prepared is stated to be easily soluble in water.
Wassermann, Keysser and Wassermann(11) made experiments with it,
chemotherapeutically, on animal tumors. When the solution was injected
into mice tumors the latter turned red, accompanied by the softening
of the tumor after the third injection and complete resorption after
ten injections, unless the dose used was too great for the animal. In
that case death often occurred. Good results were also reported, in
connection with this experiment, on four different strains of mouse
carcinoma and one strain of mouse sarcoma. In the latter case, relief
was found sooner but the former disappeared more slowly. Another
preparation was made later(12) and introduced into mice intravenously
and again found to have good results.

The following is the structure of 2-selenocyanideanthraquinone--

      O
      C      SeCN
  /\ / \ /\ /
 |  |   |  |
 |  |   |  |
  \/ \ / \/
      C
      O

which has also been reported to have medicinal uses(13).

P. Ehrlich and Hugo Bauer(14) synthesized from p.p′-diamino-diphenyl-
methane the red dye 3,6-diaminoselenopyronine.

         CH
     /\ /  \\ /\
    |  |     |  |
 H₂N|  |     |  |NH₂
     \/ \  // \/
         Se

The dye has been used upon mice and caused pronounced edema. The
toxicity of both the selenopyronine and the corresponding sulphur
compound was compared under similar conditions in the same experiment,
and it was found that the selenium dye was toxic in 1/3000 gram, but
the sulphur dye was toxic in 1/2500 gram per twenty gram weight of the
animal.

This physiological activity was noted years ago with the inorganic
compounds of selenium and Berzelius(15) described the poisonous effect
of hydrogen selenide quite impressively; “In order to get acquainted
with the smell of this gas I allowed a bubble not larger than a pea to
pass into my nostril; in consequence of its smell I so completely lost
my sense of smell for several hours that I could not distinguish the
odor of strong ammonia even when held under my nose. My sense of smell
returned after five or six hours, but severe irritation of the mucous
membrane set in and persisted for a fortnight.” The writer has been
working on the gas for some time and was also quite seriously affected
once, the injury persisting for many days. That it is more poisonous
than the hydrogen sulphide is well known.

Bruere(16) showed that when hydrogen sulphide was passed into blood
solution sulphemoglobin was produced in considerable quantity, due
to the chemical action of sulphur and hematin. He stated further
that sulphemoglobin may be found in animal blood when a large
amount of the gas has been inhaled. He made selenhemoglobin in the
same manner. Sixteen years later, Clarke and Hurtley also proved
that selenhemoglobin may be made by passing hydrogen selenide into
blood(17). These experiments may be interpreted to mean that the
oxy-hemoglobin is transformed into an organic complex of sulphur or
selenium, and that the transference may be more rapid and powerful in
the case of hydrogen selenide.

Biological investigations have sufficiently proved that dyestuffs of
the phenazine, oxazine, thiazine, acridine series show an injurious
effect on protozoa, especially those dyes containing substituted amino
groupings and of a simple structure(18). In the case of the thiazine
dyes of the methylene blue class, the physiological importance has well
recognized in their use as feeble antiseptics and analgesics. Ehrlich
and Guttmann(19) initiated the use of methylene blue as an antiperiodic
and its use in that line has been continued.

In the field of the selenazine dyes, pharmacologists have not yet paid
much attention to them, on account of the newness of the discovery, but
P. Karrer claims that they are indisputably “vital dyestuffs”(20). The
prospect of synthesizing selenazine dyes and their use as drugs seems
to be bright, judging from the fact that they are easily prepared and
capable of many combinations, especially of the ease with which they
form organic complexes with arsenic compounds.

             NO₂            NH   NO₂           NH  NO₂ (I)
  /\         /\        /\ /    \ /\        /\ /  \ /\
 |  |NH₂  Cl|  |      |  |      |  |      |  |    |  |
 |  |       |  |    = |  |      |  |    = |  |    |  |
 |  |SeH  NC|  |NO₂   |  |SeH   |  |NO₂   |  |    |  |NO₂
  \/         \/        \/      / \/        \/ \  / \/
                             O₂N               Se

Formula (I) is known, as 1, 3-dinitrobenzoselenazine(21), which
was obtained by the action of picryl chloride on the zinc salt of
o-aminoselenophenol; the product (picrylaminoselenophenol) being
then treated with alkali and thus converted to the dye, which upon
experimentation showed marked effects upon protozoa and bacteria.

      N
  /\ /  \ /\                      N
 |  |    |  |      NH₂       /\ //  \ /\       (II)
 |  |    |  |      /\       |  |     |  |
  \/ \  / \/   +  |  |   =  |  |     |  |
      Se          |  |       \/ \\  / \/
      Cl           \/             Se
                  HO₃As             \
                                     NH
                                     /\
                                    |  |
                                    |  |
                                     \/
                                  HO₃As

Formula (II), known as 3-(p-phenylarsonic)-aminoselenazine, is red
in dilute alkali and green in mineral acid, and is a typical dye
in a series from the coupling of selenodiphenylamine with arsenic
compounds. All possess similar toxicity as the thiazine dyes(20). Other
selenazines are listed in the bibliography(22).

No less than half dozen thioureas are commonly used as drugs.
Thiourea itself paralyzes the nerve centers, and is employed
commercially for photograph fixing and for removing stains from
negatives; thiuret, C₆H₇N₃S₂, serves as a substitute for iodoform;
thiosinamine-ethyliodide, or tiodine, IH₅C₂H₂NCSNHC₃H₅, is used
for relief of lesions of the central nervous system; allylthiourea
or thiosinamine, (NH₂)SC.NHCH₂CH:CH₂, for aiding the absorption of
connective tissues, for treatment of burns, keloids, urethral diseases,
sclerotic conditions of the ear(23).

Selenocarbamide and a number of its derivatives have been prepared and
studied. One class of seleno ureas has been patented as pharmaceutical
products by Chem. Fabrik von Heyden(24), and are prepared by the action
of hydrogen selenide on alkylcyanamides,

 RNH.CHN + H₂Se = RNH.CSe.NH₂

They possess pronounced therapeutic value and, serve as intermediate
products in the production of more stable alkyl halide additive
compounds. Other carbamides ranging from seleno urea itself(25), (III)
and a cyclic urea(26) (IV) are described in the literature:

      NH₂                CH₂-Se
     /                   |    \
 Se:C     (III)          |     C:NH  (IV)
     \                   |    /
      NH₂                CH₂-NH

The latter, known as ethylene-selenourea, may be classified also in the
azole group as 2-iminotetrahydroselenazole (V).

 H₂C----NH
   |    |     (V)
 H₂C   C:NH
    \  /
     Se

The literature for the other normal carbamides is listed in the
bibliography(27).

Selenoantipyrines, selenosaccharine, selenoindigoes have also been
prepared.

Thiophene and its derivatives are of considerable therapeutic interest.
Thiophene itself is found to be useful in lessening the elimination
of sulphuric acid in urine, and is employed in the dermatological
practice. Sodium thiophene sulphonate, thiophenetetra-bromide,
thiophene diiodide, are all medicinals(23).

A number of selenophenes are recorded in the literature. Their relation
to the selenazoles may be easily seen from the following formulas:

   CH--CH          CH--N
   ||  ||          ||  ||
   CH  CH          CH  CH
    \  /            \  /
     Se              Se

 Selenophene     Selenazole

Dimethyl selenophene was prepared from acetonyl acetone and phosphorous
pentaselenide,

      CH₃                    CH₃
     /                      /
 HC=C                   HC=C
  |  \                   |  \
  |   OH  +  P₂Se₅  =    |   Se
  |   OH                 |  /
  |  /                  HC=C
 HC=C                       \
     \                       CH₃
      CH₃

The compound thus obtained is stated to have the same odor as
thiophene, but no mention is made in regard to its uses(28).
Selenophene was prepared from sodium succinate and phosphorous
triselenide, or by conducting ethylselenide through hot tubes(29).

Some selenazoles find application also in medicine. At present only
the isoazoles are known to have physiological uses. One of them was
prepared from anthraquinone selenocyanide, by the action of ammonia
under pressure(30).

         NH₂H          N-Se
      O                ||
      C  SeCN          C
  /\ / \ /\        /\ / \ /\
 |  |   |  |   =  |  |   |  | + HCN + H₂O
  \/ \ / \/        \/ \ / \/
      C                C
      O                O

Another type of azoles, benzoselendiazole (piaselenol) and five of its
derivatives, have been also described as medicinals(31). The diazole
itself has the following structure,

       N                    N
  //\ /|\             //\  / \
 |   | | Se    or    |   ||   Se
  \\/ \|/             \\/  \ /
       N                    N

Diazoles of the following structure are also known, but no data were
found, regarding their physiological action(32):

      N-N                              N-N
     /   \                           //   \\
 CH₃C     CCH₃                  C₆H₅C       CC₆H₅
     \   /                           \     /
      Se                               Se

 Dimethyl-seleno-diazole      Diphenyl-seleno-diazole

Sulphides and disulphides have curative power. Dimethylsulphide is
used for internal treatment, di-o-aminophenyldisulphide is used for
intramuscular injections. Diallyl sulphide is also a medicament.
Methyl selenide has some effect on the internal parts of the body(33).
Hanzlik and Tarr(34) at the American University Experimental Station,
showed that a number of selenium compounds act as skin irritants: e.g.,
dichlorodiethyl selenide, dichlorovinyl selenide, trichlorodiethyl
selenide and selenium mustard oil. The first mentioned proved as potent
as the sulphide, but the others fell somewhat below in their effects.
Diantipyryl selenide is another therapeutical agent(35).

The diselenides occupy an important place of their own. The
selenophenols do not remain unchanged in the air, but are always
oxidized to the diselenides, which can be again reduced to the
selenophenols. So far only the diselenides of anthraquinone and their
phenols are recognized remedies(36).

TINCTORIAL REVIEW

Many of the seleno organic compounds are colored, while the
corresponding sulphur derivatives are colorless.

     HC-CH                   HC-CH
     || ||                   || ||
     HC CH                   HC CH
      \ /                     \ /
       O                       S

 Furane, colorless     Thiophene, colorless
     liquid                   liquid

        HC--CH                       HC--CH
        ||  ||                       ||  ||
        HC  CH                       HC  CH
         \  /                         \  /
          NH                           Se

  Pyrrol, colorless liq.      Selenophene, yellow liq.
 but turns brownish in air    after repeated extraction[B]

This brings selenophene more akin to pyrrole than thiophene, but the
group -NH- in the molecule of pyrrole is an auxochrome. The selenium
atom in a cyclic compound also acts like an auxochrome.

Selenoantipyrine(37),

      C₆H₅
      N
     / \
 CH₃N   CSe
    |   |
 CH₃C===CH

forms pure yellow crystals from alcohol, while the corresponding
compounds of oxygen and sulphur are colorless.

Similarly, the 2-methyl-4-selenoquinazolone is deep brown in color,
while the thio compound, prepared by Bogert and Hand(38) is light brown
or yellow and the corresponding oxygen compound is colorless or nearly
so.

Diethyl selenide (C₂H₅)₂Se, is a yellowish heavy oil of unpleasant odor.
It combines readily with chlorine to form a chloride (C₂H₅)₂SeCl₂, and
the latter is oxidized by nitric acid to form an oxide (C₂H₅)₂SeO,(39).
Diethyl sulphide is a colorless syrupy liquid, as well as diethyl amine
and diethyl ether.

The gradation of color is quite pronounced in the case of
selenonaphthene quinone(40).

      CO         CO         CO         CO
  /\ / \     /\ / \     /\ / \     /\ / \
 |  |   CO  |  |   CO  |  |   CO  |  |   CO
  \/ \ /     \/ \ /     \/ \ /     \/ \ /
      O          S          NH         Se

It would be most natural to conclude that the chromophore :CS is more
powerful than :CO, and that :CSe is most powerful of all, as shown in
our study of quinazoline compounds. It would equally follow that :S is
a more powerful color-forming radical in a cyclic compound than that of
:O; and :NH than that of :S; and :Se again most powerful of the whole
series.

Lesser and Weiss(41) in their research on selenoindigo stated that the
selenium dyestuff, on account of its greater molecular weight than
sulphur, shows a deeper blue. This hypothesis meets a difficulty in the
case of coumorandione, thionaphthenequinone and isatin series, where
the -NH- radical has an atomic weight of 15, and -S- 32, and showed the
reversed order of color. This seems to be the case in the selenophene
series also. Therefore this theory is not without exceptions.

The diselenides present a very interesting study also. Methyl
disulphide is colorless, but methyldiselenide(42) is a reddish
yellow liquid. Methyl disulphide only becomes yellow when it is
treated with chlorine, and in such cases (CH₃)₂S₂Cl₂ is formed(43),
in yellow rhombic crystals. Ethyldisulphide is colorless: ethyl-
disulphidedichloride is a faint yellow oil(44). But the corresponding
ethyldiselenide is a red liquid(45). Phenyl disulphide is colorless,
and phenyldisulphide dibromide is of mother-of-pearl appearance, and
practically colorless(46), while phenyl diselenide forms pure yellow
needles(47), and phenyldiselenide dibromide orange red ones.

While phenyldisulphide is colorless, when an auxochrome group is
added, such as NH₂, the compound is colored. This is the case with
o-diaminodiphenyldisulphide(48) which is yellow both in solution and
in crystalline form. In other words, an auxochrome in addition to the
chromophore group transforms a colorless chromogen into a colored one.
Therefore groups like -S.S- and -Se.Se- are chromophores in the same
sense as -N:N-. This is in agreement with the chromophore ideas of Hugo
Kaufmann. The -Se.Se- is a more powerful chromophore than -S.S-.

This brings one directly to the inquiry as to why 2-phenylbenzo-
selenazole, which contains a :Se radical, should be colorless; and that
even 6-nitro-2-phenylselenazole, with the addition of a chromophore
NO₂, should be only faintly colored. The benzothiazoles, their isomers
and derivatives are mostly colorless, and similar causes are probably
responsible in the case of the phenylbenzoselenazole, for its lack of
color. But when this selenazole is combined with another chromophore,
for example an azomethine grouping, the result is a more positively
colored compound (in this case benzalaminoselenazole), the crystals
being yellow. The corresponding thiazole derivative is light colored.

The tinctorial value of the selenium derivative is further evidenced
by the ease with which it forms azo dyes and the deep colors of the
latter. This was observed when 6-amino-2-phenylbenzoselenazole was
diazotized and coupled with B-naphthol, salicylic acid, etc. The
corresponding aminothiazole has been considered difficult to diazotize,
on account of its insolubility in hydrochloric acid, cold or hot, but
the aminoselenazole dissolves readily and completely, the coupling
is almost instantaneous, and the dyes obtained are mostly red and of
metallic lustre. In view of the stability of benzoselenazoles toward
hot concentrated acids (with the exception of nitric, when nitration
ensues) and alkalis, these dyes may prove of some commercial interest.

The azole dyes of the benzoselenazole have been exposed to light for
weeks, and also exposed to acids and alkalis, and have been found to be
quite fast.

EXPERIMENTAL

Preparation of 2-methyl-4-selenoquinazolone

Busch prepared quinazolines by the action of o-amino or o-nitro
benzylamine with phosgene, and thioquinazolines with carbon
disulphide(51):

      CH₂NH₂                    CH₂-NH
     /                         /    |
 C₆H₄          + COCl₂  =  C₆H₄     |     + 2HCl
     \                         \    |
      NH₂                       NH--CO

      CH₂NHC₆H₅                 CH₂-NC₆H₅
     /                         /    |
 C₆H₄            + CS₂  =  C₆H₄     |     + H₂S
     \                         \    |
      NH₂                       NH--CS

Accordingly the same reaction was tried with o-nitrobenzylamine,
prepared by the method of Lellmann and Stickel(50), using carbon
diselenide(51). The reaction seemed to work, but the mixture formed was
difficult to extract and it appeared that other reactions took place
at the same time, due to the impurity of the carbon diselenide, as the
latter has never been prepared in the pure state.

Another method, which is equally attractive because of its simplicity,
is that of Gabriel and Stelzner(52),

      CHO                      CH=N
     /             NH₂        /   |     H₂O
 C₆H₄       +      |   =  C₆H₄    |  +
     \         H₂N-CO         \   |     NH₃
      NH₂                      NH-CO

In accordance with the above reaction o-aminobenzaldehyde should work
with equal ease with selenocarbamide, but the initial materials were
not available.

The reaction which was used successfully was that of Bogert, Breneman
and Hand(53),

      NH₂                   NHCOR           N=CR
     /                     /               /   |
 C₆H₄      + (RCO)₂O → C₆H₄          → C₆H₄    |
     \                     \               \   |
      CSNH₂                 CS-NH₂          CS-NH

     ↑                     ↑                or

    H₂S                   H₂S                N=CR
                                           /  |
     +                     +           C₆H₄   |
                                           \  |
      NH₂                   NHCOR           C=N
     /                     /                |
 C₆H₄      + (RCO)₂O → C₆H₄                 SH
     \                     \
      CN                    CN

The hydrogen selenide used in the reaction was prepared from FeSe by
the action of hydrochloric acid, or by heating paraffin and selenium,
in the proportion of four to one respectively, at 335° to 350°C(54).

The selenoquinazoline was prepared from anthranilic nitrile by the
following methods--the anthranilic nitrile being prepared from
o-nitraniline(57),

(a) 20 grams of acetyl-anthranilic nitrile was dissolved in absolute
alcohol, and dry hydrogen selenide and dry ammonia passed into the
solution for three hours. The quinazoline crystallized out gradually
on cooling was filtered out and recrystallized from dilute alcohol. The
yield was about ten per cent.

(b) 10 grams of acetyl-anthranilic nitrile was heated in a sealed
tube at 110° with alcohol saturated at zero degrees with dry hydrogen
selenide and dry ammonia. After five hours, the tube was taken out and
the quinazoline crystallized out on cooling. Yield was about sixteen
per cent.

As hydrogen selenide was somewhat unstable and did not dissolve freely
in alcohol, freshly prepared sodium selenide was used in the following
method and was found to be more satisfactory. It was prepared from
sodium hydroxide in absolute alcohol by passing dry hydrogen selenide
into the solution for about three hours. In the beginning and end of
the reaction, nitrogen was used to exclude the oxygen of the air. The
selenide was collected and dried in an atmosphere of nitrogen, and then
in a vacuum, in presence of phosphorus pentoxide. When thus prepared,
sodium selenide was colorless, but on exposure to air it turns reddish
and finally dark colored. The C. P. selenide on the market was black
and was found to be entirely useless.

(c) 20 grams of anthranilic nitrile and fifty grams of sodium selenide
were mixed and heated in a distilling flask in an atmosphere of
nitrogen, and forty grams of acetic anhydride dropped into the flask
very slowly. The temperature was kept at 115° for half an hour and then
raised to distill off the acetic acid formed in the reaction, as the
condensation hardly went to completion in the presence of any trace of
acetic acid. The whole process took an hour and a half. The flask was
removed from the oil bath and, after cooling, dilute alkali was run in,
in successive portions, to dissolve out the quinazoline. Into the clear
alkaline extracts carbon dioxide was bubbled for an hour, and common
salt then added. The precipitate was recrystallized several times from
twenty-five per cent. alcohol. The yield was from twenty to twenty-five
per cent.

(d) 10 grams of anthranilic nitrile, twenty grams of acetic anhydride,
and twenty-five grams of sodium selenide were mixed in a sealed
tube and heated together for three hours and a half at 110°-115°. The
condensation product was crystalline when the tube was cooled to room
temperature. The contents of the tube were extracted with dilute alkali
as before, filtered, precipitated by carbon dioxide, and recrystallized
from dilute alcohol. The yield was not over twenty per cent.

(e) An attempt was made to make o-aminobenzoselenamide, and from the
latter, by treatment with acetic anhydride, to form the quinazoline,
but the yield of the amide was too small to carry the reaction further.

The substance prepared by the above methods crystallizes from dilute
alcohol in needles or prisms of dark brown color. It melts at 213.5°
(corr.). It dissolves readily in hot alcohol but on concentration
sometimes forms a sticky mass with a peculiar but not unpleasant odor.
It dissolves readily in alkalis and is slightly soluble in hot benzene
and chloroform, but insoluble in hot water. Crystals purified from (a)
were analyzed and gave the following results:

            Calculated for       Found
             C₉H₈N₂Se          I       II

 Carbon        48.38%        48.45%   48.62%
 Hydrogen       3.61          3.82     3.52
 Nitrogen      12.55         12.51    12.66
 Selenium      35.46         35.60    35.42

The crystals on standing in the presence of air and light decomposed
with separation of finely divided selenium and methyl quinazolone.

Analysis of Selenium Organic Compounds

In the quantitative determination of selenium in quinazoline
the method adapted by Becker and Meyer was found to be quite
satisfactory(56). Other methods are listed in the bibliography(57).

In the ultimate analysis of carbon and hydrogen, the ordinary absolute
method was followed with the use of copper oxide, lead chromate,
and lead peroxide in the tube. In the determination of nitrogen
the ordinary absolute method was also followed excepting that a
considerable quantity of specially prepared lead chromate powder was
mixed with the sample in a number six porcelain boat. This was found to
be desirable when the dinitroselenazole was burned. Selenium dioxide,
which is a solid, seems to be formed in the tube and carried away by
the current of carbon dioxide with some difficulty. In such a case the
analysis usually took four hours after the combustion had actually
started. In the carbon and hydrogen determination selenium dioxide was
easily absorbed in the presence of oxygen gas.

Preparation of 2-Phenylbenzoselenazole

The first method employed was a modification of the method described
by Fromm and Martin(58). Method (b) is an adaptation of the method for
preparing benzothiazoles.

(a) Twenty grams of benzanilide was mixed in a pyrex flask with 160
grams of selenium dust and the flask placed in a nitrate bath under an
air condenser. After heating for an hour at 220°C., the temperature
was raised to 250°C., and kept at 250°-280°C. for sixteen hours. The
dark mass was extracted with hot concentrated HCl, the acid extracts
filtered through glass wool using a hot water funnel. The combined
extracts were poured into a large volume of water when the selenazole
precipitated out immediately; it was recrystallized from alcohol.
In some cases it was necessary to dissolve in hot HCl again and to
recrystallize. The yield was twelve per cent.

The above method has the disadvantage that water is formed in the
reaction and this in turn reacts upon benzanilid at the higher
temperature necessary (as selenium only melts at 217°C.), decomposing
the benzanilid into aniline and benzoic acid.

      NHCOC₆H₅              N
     /                     / \\
 C₆H₄         + Se  =  C₆H₄    C-C₆H₅ + H₂O
     \                     \  /
      H                     Se

      NHCOC₆H₅              NH₂
     /                     /
 C₆H₄         + HOH =  C₆H₄    + HOOC-C₆H₅
     \                     \
      H                     H

Furthermore benzanilid boils at 160°C. and at such high temperatures as
250°C. and over some of it is apt to be driven off.

(b) 106 grams of benzaldehyde were heated with 93 grams of redistilled
aniline at 120°C., for two hours or until the solution was clear. The
clear benzalaniline was then poured into 160 grams of selenium dust
in a pyrex flask on a sand bath, the flask being connected with an
air condenser as before. In order to distribute the flame to better
advantage over the bath, an air space was made between the Meker
burner and the bath by introducing a wire gauze. Hydrogen selenide was
evolved freely. Complete reaction took three days. The extraction and
recrystallization were the same as in the former case. The yield was
sixty per cent.

The selenazole crystallizes in colorless long needles, melting at
117.5°C. (corr.) Fromm and Martin(58) gave the melting point as
117°C. It is insoluble in water, and in the following solvents it is
lightly soluble in the cold, more easily hot: ether, methyl alcohol,
acetone, acetic acid, acetic anhydride, chloroform, and nitrobenzene.
It is difficultly soluble in ethyl alcohol, ethyl acetate, and carbon
tetrachloride, in the cold, but easily soluble hot.

Mononitro Derivative

The mononitro derivative of the selenazole, 6-nitro-2-phenylbenzo-
selenazole, was prepared by nitration with nitric acid at a low
temperature:

Twenty-five grams of the selenazole were dissolved in 150 grams of
concentrated sulphuric acid, keeping the temperature below the room
temperature until complete solution took place. It was then cooled
on a freezing mixture and a mixture of sulphuric and nitric acids
(previously prepared and cooled by mixing 9.5 grams of nitric and
fifteen grams of sulphuric acids) slowly dropped into it in the course
of half an hour, using mechanical stirring for four hours. The solution
was then poured into two liters of water (ice water), filtered, dried,
and recrystallized from acetic acid, and alcohol with the help of
animal charcoal. The yield was 95 per cent.

This nitro compound crystallizes in flattened needles of a light
yellow color. It melts at 202.4°C. (corr.). It is very insoluble in
water; but soluble in hot acetic acid, acetic anhydride, nitrobenzene,
nitrotoluene, toluene, benzene, alcohol, and difficultly soluble when
cold. The crystals were analyzed and gave the following results,

                Calculated for            Found
                 C₁₃H₈N₂O₂Se            I       II

 Nitrogen           9.24%             9.36%    9.48%

Monoamino Derivative

The conversion of mononitro compound to 6-amino-2-phenylbenzoselenazole
was accomplished by the action of tin and hydrochloric acid as follows:

30.3 grams of nitro compound were mixed with 42 grams of twenty mesh
tin in a liter flask, immersing the latter in cold water. 175 cc.
of conc. HCl were slowly added to the flask. In some cases it was
necessary to apply initial heating but when once the reaction started
it took place rapidly. After the effervescence had abated, the flask
was heated over a free flame, under a return condenser, for two hours.
The solution usually turned to a pasty mass, due to the formation of a
tin double salt. The mixture was dissolved in a large volume of water
and heated on a water-bath, the precipitate filtered out, washed, and
preserved. The clear filtrate was treated with concentrated alkali, in
excess, the separated amine collected, washed with water, dried and
recrystallized from alcohol, using bone-black. The precipitate set
aside was treated with strong alkali, the insoluble residue washed,
recrystallized, and added to the main product. The yield was 75 per
cent.

This amine crystallizes from alcohol in fine yellowish needles,
melting at 201.2°-202.3°C (corr.). It is insoluble in water and ether,
difficultly soluble in the hot; and fairly soluble in aniline. A pure
sample was analyzed and gave the following results:

                 Calculated for        Found
                   C₁₃H₁₀N₂Se        I       II

 Nitrogen           10.25%         10.34%   10.42%
 Carbon             57.18          57.17    57.00
 Hydrogen            3.69           3.79     3.85

Decomposition of Monoamino Derivative

Five grams of the monoamino compound were mixed with powdered KOH,
heated together until the mixture just melted, and maintained in that
state for a few minutes. When the latter had cooled down to room
temperature, cold water was poured over the mixture. The filtered
solution was acidified until no further precipitate was formed. The
precipitate was collected and recrystallized from water, m.p. 121°C.

One gram of this solid was placed in a test tube, provided with a cork
and a delivery tube, and heated with soda lime; a liquid with the smell
of benzene was collected in another test tube cooled with water. When
this liquid was treated with a few drops of nitric acid mixture the
smell of nitrobenzene was given off. A gram of the crystals was heated
with concentrated sulphuric acid and alcohol when the odor of ethyl
benzoate was noted.

Monacetyl Derivative

Five grams of the monoamino selenazole were heated on a water-bath with
10 cc. of acetic anhydride until the solution was clear, which took
about two hours. 100 cc. of water were poured into the mixture, which
was then neutralized with dilute ammonium hydroxide. The precipitate
was filtered, decolorized by animal charcoal, and recrystallized from
dilute alcohol.

The acetyl compound, 6-acetamino-2-phenylbenzoselenazole, forms
colorless crystals, melting at 188.1°-.7°C. (corr.). It is insoluble in
ether, benzene, carbon disulphide; slightly soluble in toluene; soluble
in alcohol, ethyl acetate, amyl acetate, acetone, and acetic acid. A
pure sample was analyzed and gave the following result,

                  Calculated for
                   C₁₅H₁₂N₂SeO            Found

 Nitrogen             8.88%           8.92%   8.68%

Monobenzylidene Derivative

Five grams of the monoamino compound were dissolved in 200 cc. absolute
alcohol with the addition of 3 cc. of benzaldehyde and the clear
solution was boiled on a water-bath, with a return condenser, for two
hours. After the solution was boneblacked, the yellow precipitate was
recrystallized from carbon disulphide. The yield was 90 per cent.

It crystallizes in yellow plates, melting at 156.7°-157.6°C., soluble
in benzene, ether, ethyl alcohol, carbontetrachloride, acetone, but
difficultly soluble in ligroin. An analysis of the crystals showed the
following result,

                 Calculated for
                   C₂₀H₁₄N₂Se            Found

 Nitrogen             7.75%          7.92%  7.68%

An Azo Dye

Five and four tenth grams of the monoamino compound were dissolved
in hot conc. HCl, cooled in ice, and diazotized with sodium nitrite
solution, until starch iodide paper showed excess nitrous acid.
The diazotization was performed in ice, with mechanical stirring,
and required about an hour. The diazo solution was poured into a
solution of 3 grams B-naphthol in 8 grams of NaOH and 60 cc. of water,
while gradually stirring. A very deep red solution formed. This was
acidified with excess HCl, salted out by NaCl, and crystallized from
aniline-alcohol mixture. In the pure state, it is a deep red powder,
with a metallic lustre when rubbed, melting at 284.2°C. An analysis
showed the following result,

                 Calculated for
                  C₂₃H₁₅N₃OSe          Found

 Nitrogen             9.81%            9.75%

Dinitro Derivative

The nitration for the production of dinitro derivative was at first
carried out under the same conditions as in the preparation of
mononitro compound and after the latter was formed more nitric acid
mixture was added with the addition of heat: conc. sulphuric acid,
keeping it below room temperature. It was then cooled in a freezing
mixture and half the volume of a nitric acid mixture (prepared and
cooled by mixing 19 grams of nitric and 30 grams of sulphuric acids)
was introduced very slowly to the selenazole solution through a
dropping funnel, maintaining at this temperature for two hours (using
mechanical stirring). The remaining half of the nitric acid mixture
was then slowly introduced and the flask was heated on a water-bath
for two hours. The solution was poured into two liters of water, the
precipitate filtered off, dried and recrystallized several times from
acetic acid. The yield was 80 per cent.

This dinitro compound crystallizes in fine yellow needles, m. p.,
246.8°C. (corr.), very insoluble in water, but soluble in hot acetic
acid, acetic anhydride, nitrobenzene, nitrotoluene, ethyl alcohol, and
difficultly soluble cold. It was analyzed and the following results
were found,

                   Calculated for           Found
                    C₁₃H₇N₃O₄Se           I       II

 Nitrogen              12.07%           12.30%  12.12%

Diamino Derivative

The conversion of the dinitro to diamino derivative was accomplished in
the same manner as the reduction of the mononitro derivative excepting
that twice as much tin and HCl were used.

This diamino compound crystallizes in yellowish glistening needles from
alcohol and pyridine; m. p., 269°-270.5°C.; was analyzed and gave the
following results,

                 Calculated for        Found
                   C₁₃H₁₁N₃Se        I       II

 Nitrogen             14.6%        14.4     14.7

Diacetyl and Dibenzylidene Derivatives

The diacetyl and dibenzylidene compounds were also prepared from these
diamino derivatives. The former crystallizes in cubes from dilute
alcohol; m. p., 307°C (Corr.) and the latter in beautiful yellow plates
from carbon disulphide, m. p., 195°-196°C. (Corr.). An analysis of
these two compounds showed the following results,

            Calc. for        Calc. for           Found
           C₁₇H₁₅N₃O₂Se      C₂₇H₁₉N₃Se        I      II

 Nitrogen      9.05%          11.21%         9.21%   11.43%

Dyeing with Azo Dyes

Both the monoamino and the diamino derivatives form intensely colored
dyes when diazotized and coupled with phenols and aromatic amines. The
dyes formed are fast to light. In the following table silk is given to
represent the fabrics used. Wool and cotton were dyed similar shades,
though with slight variation. Each silk sample was dyed in acid or
alkaline baths as indicated and each bath contained 0.01 gram in twenty
cc. solution:

                    Diazo.       On        Diazo.       On
    Coupler        monoamine    silk      diamine      silk

 Phenol            deep red    v. light    (alk)      yellow
                    (alk)       yellow    deep red

 Dimethylaniline    orange      light    orange-red   yellow
                    (acid)      yellow     (acid)

 P-nitraniline      light                 brownish    grayish
                    brown                  (acid)      brown
                   (acid)

 P-toluidine        light                 brownish    brownish
                    brown                  (acid)
                   (acid)

 Pyrogallic         dark       grayish      dark      grayish
 acid               brown                   brown
                   (acid)                   (alk)

 Salicylic         reddish      light        red       brown
 acid               (alk)       brown       (alk)

 B-naphthol        deep red     pink      deep red      red
                    (alk)                   (alk)

 Sulphanilic        light     brownish      brown      brown
 acid               brown                   (alk)
                    (alk)

 A-naphthylamine    light     brownish     yellow     yellow
                    brown                  (acid)
                   (acid)

 Resorcinol        purple       red         dark      deep red
                   (alk)                   purple
                                           (alk)

BIBLIOGRAPHY

  1. Berzelius, Annales de Physique et Chimie (2) 9, 239, 356 (1818).

  2. Gmelin-Kraut, “Handbuch der Anorg. Chemie” I (1) 705-804; Roscoe
     and Schorlemmer, “Treatise on Chemistry” I, 467-82 (1920);
     Browning, “Introduction to the Rarer Elements,” 144-52 (1917).

  3. Victor Lenher, J. Ind. Eng. Chem., 12, 597 (1920).

  4. Le Seleneum et ses applications actuelles, Chimie et Industrie
     (1919) 245.

  5. C. R. Boggs, U. S. A., 1,249,272; J. Ind. Eng. Chem. 10, 117-8
     (1918).

  6. Duhamel & Robiere, Compt. rend. soc. biol. 72, 670 (1913); Am.
     Chem. Abs. 7, 2624 (1913).

  7. B. G. Duhamel, Compt. rend. soc. biol., 72, 865 (1913); Am. Chem.
     Abs. 7, 2971 (1913).

  8. Duhamel & Juillard, Compt. rend. soc. biol., 72, 714 (1913); Am.
     Chem. Abs., 7, 2624 (1913).

  9. B. G. Duhamel, Compt. rend. soc. biol., 82, 724-6 (1919); Am.
     Chem. Abs. 14, 2383 (1920).

 10. Wassermann, D. R. P., 261,556; 286,950; 287,020.

 11. A. v. Wassermann, Keyser, & M. Wassermann, Duet. Med. Woch., 37,
     2389 (1911); Am. Chem. Abs., 6, 650 (1912).

 12. A. v. Wassermann & Hansmann, Berl. klin. Woch., 49, 4, (1911); Am.
     Chem. Abs., 6, 890 (1912).

 13. Anthraquinone dyes, D. R. P., 256,667.

 14. P. Ehrlich & H. Bauer, Ber., 48, 502 (1915).

 15. Berzelius, Lehrbuch (5 Aufl.) 2, 213; Roscoe and Schorlemmer,
     “Treatise on Chemistry,” I, 473 (1920).

 16. Bruere, J. Anat. Physiol., Oct., (1891).

 17. T. W. Clarke & W. H. Hurtley, J. Physiol., 36, 62 (1907).

 18. Hugo Bauer, Ber., 47, 1873 (1914).

 19. Ehrlich & Guttmann, Berl. klin. Woch. (1891) 28; U. S. Disp., 20th
     Edition.

 20. P. Karrer, 49, 597 (1916); Ber., 51, 190 (1918).

 21. Hugo Bauer, Ber., 47, 1873 (1914); D. R. P., 261,969; Friedl., 11,
     1124 (1913).

 22. Selenazines, D. R. P., 280,713; 261,793.

 23. U. S. Disp., 20th Edition.

 24. D. R. P., 305,262; 305,263; Am. Chem. Abs., 13,325 (1918).

 25. Bull. soc. chim., 41, 599; Compt. rend., 99, 1154-7 (1885); Brit.
     Chem. Abs., 50, 376 (1885); A. Ch., (6) 9, 294, 303, 323.

 26. W. Baringer, Ber., 23, 1003 (1889).

 27. P. Spica, Gazz. chim. ital., 7, 90-9 (1877); Brit. Chem. Abs.,
     (1877) II, 189; Compt. rend., 99, 1154 (1884); 100, 1296 (1885);
     Frerichs, Arch. Pharm., 241, 180, 196; Beil., (1921) III, 295, 261.

 28. C. Paal, Ber., 18, 2255 (1885); Gazz. chim. ital., (I. Zoppellari)
     24, II, 399, (1894).

 29. Ida Foa, Gazz. Chim. ital., 39, II, 527, (1909); C-B., (1910) I,
     837.

 30. D. R. P., 264,139.

 31. O. Hinsberg, Ber., 22, 862, 2895 (1889); D. R. P., 261,412.

 32. J. prakt. Chem., (1904) II, 69, 509.

 33. E. Abderhalden, Hand. Biol. Chem., III, 2, 954.

 34. Hanzlik & Tarr, Am. Univ. Ezpt. Sta., J. Pharmacol, 14, 221-8
     (1919).

 35. Hochst, D. R. P., 299,510.

 36. D. R. P., 264,940; 264,961.

 37. A. Michaelis & M. Stein, Ann., 320, 32 (1902).

 38. Bogert & Hand, J. Am. Chem. Soc., 25, 377 (1902).

 39. B. Bathke, Ann., 152, 210 (1869); Ann., 185, 331; Richter,
     Organische Chemie, I, 166.

 40. Lesser & Schoeller, Ber., 47, 2293 (1914).

 41. Lesser & Weiss, Ber., 45, 1835 (1912); 46, 2653, (1913).

 42. Wohler & Dean, Ann., 97, 5 (1856); B. Rathke, Ann., 152, 211
     (1869).

 43. Cahours, Ann., 61, 92, (1847); 92, 356.

 44. H. Klinger, Ber., 32, 2195, (1899); Ann., 119, 91; 121, 108.

 45. C. A. Joy, Ann., 86, 35, (1853); B. Rathke, Ann., 152, 212, 219
     (1869).

 46. Wheeler, Z. Chem., (1867) 436.

 47. Krafft & Lyons, Ber., 27, 1762 (1894); A. Ch., (6), 20, 228.

 48. K. A. Hoffmann, Ber., 27, 2809 (1894).

 49. M. Busch, Ber., 25, 2853, (1892).

 50. Lellmann & Stickel, Ber., 19, 1605 (1886).

 51. B. Rathke, Ann., 152, 201 (1869).

 52. Gabriel & Stelzner, Ber., 29, 1313 (1896).

 53. Bogert, Breneman, & Hand, J. Am. Chem. Soc., 25, 373 (1903).

 54. Am. Chem. Abs., 3, 870 (1903); Bull. Belg. Soc. Chem., 23, 9-11.

 55. Bogert & Hand, J. Am. Chem. Soc., 24, 1035, (1902).

 56. Becker & Meyer, Ber. 37, 2551 (1914).

 57. H. Bauer, Ber. 48, 507 (1915); Lyons & Shinn, J. Am. Chem. Soc.
     1902: 1092; Fritz von Konek & O. Schleifer, Ber. 51, 850 (1918); A.
     Michaelis, Ber. 30, 2827 (1897); Ber. 48, 873 (1915); H. Frerichs,
     Arch. Pharm. 1902: 240, 656.

 58. Fromm & Martin, Ann., 401, 178 (1913).

VITA

Yü-Gwan Chen was born in Nanking, China, March 8, 1893. After
graduation from college in 1915, he further studied Chinese classics,
1915-16. He entered Case School of Applied Science, Cleveland, Ohio,
as a special student in the Department of Chemistry, 1916-17. He
registered at Columbia University to pursue graduate work in chemistry
under the Faculty of Pure Science; and was awarded the degree of Master
of Arts in 1918. From September 1919 to June 1922, he has been pursuing
research in organic chemistry in the research laboratories of Havemeyer
Hall, Columbia University.

FOOTNOTES:

[A] Not a new compound but prepared by a different method.

[B] Note--dimethyl selenophene, however, is colorless.

    Transcriber's notes:

    The diagram of 3-(p-phenylarsonic)-aminoselenazine, labelled (II),
    has been adjusted to make its structure clearer.

    The "l" in "2HCl" in the first equation under "Preparation of
    2-methyl-4-selenoquinazolone" was missing in the original.

    The following is a list of changes made to the original.
    The first line is the original line, the second the corrected one.

    selnoquinazolone prepared in the course of this research
    selenoquinazolone prepared in the course of this research

    on four different strains of mouse carcenoma and one strain
    on four different strains of mouse carcinoma and one strain

    in consequence of its smell I so completely loss my sense of smell
    in consequence of its smell I so completely lost my sense of smell

    of the phenazine, oxasine, thiazine, acridine series show
    of the phenazine, oxazine, thiazine, acridine series show

    and Se again most powerful of the whole series.
    and :Se again most powerful of the whole series.

    simplicity, is that of Babriel and Stelzner(52),
    simplicity, is that of Gabriel and Stelzner(52),

    on cooling was filtered out and recrystalized from dilute alcohol.
    on cooling was filtered out and recrystallized from dilute alcohol.

    It was prepared from Sodium hydroxide in absolute alcohol
    It was prepared from sodium hydroxide in absolute alcohol

    a sealed tube at 110° with alcohol saturated at zero degree with
    a sealed tube at 110° with alcohol saturated at zero degrees with

    took an hour and half. The flask was removed from the oil
    took an hour and a half. The flask was removed from the oil

    The precipitrate was recrystallized several times
    The precipitate was recrystallized several times

    (e) An attempt was made to make o-aminobenzselenamide,
    (e) An attempt was made to make o-aminobenzoselenamide,

    It dissolves readily in alkalies and is slightly soluble
    It dissolves readily in alkalis and is slightly soluble

    This was found to be desirable when the dinitroselezazole was burned.
    This was found to be desirable when the dinitroselenazole was burned.

    into a large volume of water when the selenozole precipitated out
    into a large volume of water when the selenazole precipitated out

    it was necessary to dissolve in hot HCl again and to recrystalize.
    it was necessary to dissolve in hot HCl again and to recrystallize.

    (b) 106 grams of benaldehyde were heated with 93 grams of
    (b) 106 grams of benzaldehyde were heated with 93 grams of

    It is difficulty soluble in ethyl alcohol, ethyl acetate, and
    It is difficultly soluble in ethyl alcohol, ethyl acetate, and

    toluene, benzene, alcohol, and difficulty soluble when cold.
    toluene, benzene, alcohol, and difficultly soluble when cold.

    from alcohol in fine yellowish needles, melting at 201.2°202.3°C
    from alcohol in fine yellowish needles, melting at 201.2°-202.3°C

    carbontetrachloride, acetone, but difficulty soluble in ligroin.
    carbontetrachloride, acetone, but difficultly soluble in ligroin.

    19 grams of nitric and 30 grams of sulphuric acids was introduced
    19 grams of nitric and 30 grams of sulphuric acids) was introduced

    in the same manner as the reduction of mononitro derivative
    in the same manner as the reduction of the mononitro derivative

    This diamino compound crystalizes in yellowish glistening needles
    This diamino compound crystallizes in yellowish glistening needles

    compounds were also prepared from this diamino derivatives.
    compounds were also prepared from these diamino derivatives.

    The former crystalizes in cubes from dilute alcohol;
    The former crystallizes in cubes from dilute alcohol;