ARSENIC DERIVATIVES
Since arsenic is well known as an insecticide in the form of lead
arsenate, arsenic acid etc., and in pharmacy, specially in the form
of salvarsan and neosalvarsan, it is not surprising that the Germans
should have endeavored to discover an arsenic derivative which would
be of value from the point of view of chemical warfare. Very early in
the war persistent rumors were circulated that the Germans were to
use arsine. These rumors led to the use of sodium permanganate in the
canister, but as far as is known, no arsine was actually used. Another
suggestion which received considerable attention from American workers
was the use of arsenides, which might decompose under the influence of
the atmospheric moisture with the liberation of arsine. Calculation of
the amount of arsenide necessary to establish a lethal concentration
of arsine showed, however, that there was no possibility of using the
material on the field.
Because of the use of arsenic trichloride in the manufacture of organic
arsenic compounds, a method of preparation was developed from arsenic
trioxide and sulfur chloride or hydrogen chloride. It was also shown
experimentally that the phosgene of the tail gas of phosgene plants
might be converted into arsenic trichloride by reaction with arsenic
trioxide. Charcoal is the catalyzer of this reaction.
Arsenic trichloride is also of interest because it was one of the
constituents of the mixture vincennite, early used by the French.
This was a mixture of hydrocyanic acid, stannic chloride, arsenic
trichloride and chloroform. While extensively used at first, it was
gradually replaced by phosgene.
Arsenic triflouride was also prepared by the action of sulfuric acid
upon a mixture of calcium flouride and arsenic trioxide. The compound
is very easily decomposed by the moisture of the air, and furthermore
is not very toxic.
Organic arsenic derivatives are the most important compounds
from the military point of view. The first substance used was
diphylchloroarsine, a white solid, which readily penetrated the
canister and caused sneezing. This was used alone, and in solution in
phenyl dichloroarsine. Later methyl and ethyl dichloroarsines were
introduced.
[Illustration: FIG. 38.—Apparatus for the Manufacture of
Methyldichloroarsine.]
METHYLDICHLOROARSINE
The Germans apparently used ethyldichloroarsine because they had no
suitable method for the preparation of methyl dichloroarsine, which is
a more satisfactory material. The Chemical Warfare Service developed
the following method of preparation of the methyl derivative. Sodium
arsenite (Na₃AsO₃) is prepared by dissolving arsenic trioxide in sodium
hydroxide solution. The action of methyl sulfate at 850 C. gives
disodium methyl arsenite, Na₂CH₃AsO₃. Sulfur dioxide reduces the
arsenite to methyl arsine oxide, CH₃AsO, which is then reacted with
hydrochloric acid to give methyl dichloroarsine. The final product is
distilled from the mixture and condensed. This material costs from two
to two and a half dollars per pound for chemicals (war prices).
Methyldichloroarsine is a colorless liquid of powerful burning odor,
which boils at 132° C. It is somewhat soluble in water and is soluble
in organic solvents. The specific gravity is 1.838 at 20° C. The vapor
pressure at 25° was found to be 10.83 mm. mercury. Not only is the
material toxic but it has remarkable vesicant properties, comparing
favorably with mustard gas in this respect.
Ethyldichloroarsine, which was used by the Germans, was prepared by
the method given above, using ethyl sulfate, but the yield was never
over 20 per cent. In general this has properties similar to the methyl
derivative.
DIPHENYLCHLOROARSINE
The best known of the arsenicals, however, is diphenylchloroarsine or
sneezing gas. Although this is an old compound (having been prepared
by German chemists in 1885), there was no method for its preparation
on a large scale when, first introduced into chemical warfare. It
was finally discovered that the interaction of triphenyl arsine with
arsenic trichloride was fairly satisfactory and a plant was erected for
its manufacture.
When pure, diphenylchloroarsine is a colorless solid, melting at 44°.
Because of this, it was always used in solution in a toxic gas or in
a shell which contained a large amount of explosive so that on the
opening of the shell the material would be finely divided and scattered
over a wide territory.
Its value lay in the fact that the fine particles readily penetrated
the ordinary mask and caused the irritation of the nose and throat,
which resulted in sneezing. This necessitated the perfection of special
smoke filters to remove the particles, after which the other toxic
materials were removed by the absorbent in the canister.
It causes sneezing and severe burning sensations in the nose, throat
and lungs in concentrations as slight as 1 part in 10 million. In
higher concentrations, say 1 in 200 to 500 thousand it causes severe
vomiting. While neither of these effects are dangerous or very lasting,
still higher concentrations are serious, as in equal concentrations
diphenylchloroarsine is more poisonous than phosgene.
Various other arsenical chemicals were developed in the laboratory,
but with one or two exceptions they were not as valuable as
diphenylchloroarsine and methyldichloroarsine and were therefore
discarded.
GERMAN METHODS FOR MANUFACTURING ARSENICALS[23]
DIPHENYLCHLOROARSINE
[Footnote 23: Norris, _J. Ind. Eng. Chem._, =11=, 825 (1919).]
“This substance (Blue Cross) was a famous gas of the
Germans and was made in large quantities. The method
used by the Germans was different from the one worked
out by the Allies, and on account of the fact that the
German method could be carried out without specially
designed apparatus and required as raw materials
substances readily obtainable, it was probably
preferable. It is doubtful, however, whether the Allies
would have made this gas, for as the result of its
use no fatalities were reported. The German process
consisted in preparing phenylarsenic acid by condensing
benzene diazonium chloride with sodium arsenite.
The acid was next reduced by sulfur dioxide to
phenylarsenous acid, which was, in turn, condensed with
the diazonium compound to form diphenylarsenic acid.
This acid was reduced to diphenylarsenous oxide, which
with hydrochloric acid yielded diphenylchloroarsine.
The chemical equations for the reactions will make
clearer the steps involved.
C₆H₅N₂Cl + Na₃AsO₃ = C₆H₅AsO₃Na₂ + NaCl + N₂
C₆H₅AsO₃Na₂ + 2HCl = C₆H₅AsO₃H₂ + 2NaCl
C₆H₅AsO₃H₂ + SO₂+H₂O = C₆H₅AsO₂H₂ + H₂SO₄
C₆H₅N₂Cl + C₆H₅AsO₂Na₂ = (C₆H₅)₂AsO₂Na + NaCl + N₂
(C₆H₅)₂AsO₂Na + HCl = (C₆H₅)₂AsO₂H + NaCl
2(C₆H₅)₂AsO₂H + 2SO₂ + H₂O = [(C₆H₅)₂As]₂O + 2H₂SO₄
[(C₆H₅)₂As]₂O + 2HCl = 2(C₆H₅)₂AsCl + H₂O.
“The entire process was carried out at Höchst. The
method used at Höchst was as follows: In preparing
the diazonium solution, 3 kg.-mols of aniline were
dissolved in 3000 liters of water and the theoretical
quantity of hydrochloric acid. The temperature of
the solution was reduced to between 0° and 5° and
the theoretical amount of sodium nitrite added.
The reaction was carried out in a wooden tank of
the usual form for the preparation of diazonium
compounds. A solution of sodium arsenite was prepared
which contained 20 per cent excess of oxide over
that required to react with the aniline used. The
arsenous oxide was dissolved in sodium carbonate, care
being taken to have enough of the alkali present to
neutralize all of the acid present in the solution
of the diazonium salt. To the solution of the sodium
arsenite were added 20 kg. of copper sulfate dissolved
in water, this being the amount required when 3
kg.-mols of aniline are used. The solution of the
diazonium compound was allowed to flow slowly into
the solution of the arsenite while the temperature
was maintained at 15°. The mixture was constantly
stirred during the addition which requires about 3
hrs. After the reaction was complete, the material
was passed through a filter press in order to remove
the coupling agent and the tar which had been formed.
Hydrochloric acid was next added to the clear solution
to precipitate phenylarsenic acid, the last portions of
which were removed by the addition of salt.
“The phenylarsenic acid was next reduced to
phenylarsenous acid by means of a solution of sodium
bisulfite, about 20 per cent excess of the latter
over the theoretical amount being used. For 100 parts
of arsenic acid, 400 parts of solution were used.
The reaction was carried out in a wooden vessel and
the mixture stirred during the entire operation. A
temperature of 80° was maintained by means of a steam
coil. Phenylarsenous acid separated as an oil. The
aqueous solution was decanted from the oil, which was
dissolved in a solution of sodium hydroxide, 40° Bé.
The solution of the sodium salt of phenylarsenous
acid was treated with water so that the resulting
solution had a volume of 6 cu. m. when 3 kg.-mols of
the salt were present. Ice was next added to reduce the
temperature to 15° and a solution of benzene diazonium
chloride, prepared in the manner described for the
first operation, was slowly added. After the coupling,
diphenylarsenic acid was precipitated by means of
hydrochloric acid. The acid was removed by means of a
filter press and dissolved in hydrochloric acid, 20°
Bé. For one part of diphenylarsenic acid, 3 parts of
hydrochloric acid were used. Into this solution was
passed 5 per cent excess of sulfur dioxide over that
required for the reduction. The sulfur dioxide used was
obtained from cylinders which contained it in liquid
condition.
“The reduction was carried out in an iron tank lined
with tiles and a temperature of 80° was maintained.
About 8 hrs. were required for the reaction. The
diphenylarsenic acid on reduction by the sulfur dioxide
was converted into diphenylarsenous oxide which, in
the presence of the hydrochloric acid, was converted
into diphenylchloroarsine, which separated as an oil.
The oil was next removed and heated in the best vacuum
obtainable until it was dry and free from hydrochloric
acid. The compound melted at 34°. It was placed in iron
tanks for shipment. The yield of diphenylchloroarsine
calculated from the aniline used was from 25 to 30 per
cent of the theoretical. No marked trouble was observed
in handling the materials and no serious poisoning
cases were reported.
DIPHENYLCYANOARSINE
“This compound was prepared by treating diphenylchloroarsine with a
saturated aqueous solution of potassium or sodium cyanide.
(C₆H₅)₂AsCl + NaCN = (C₆H₅)₂AsCN + NaCl.
Five per cent excess of the alkaline cyanide was used. The reaction
was carried out at 60° with vigorous stirring. The yield was nearly
theoretical.
ETHYLDICHLOROARSINE
“This compound was prepared at Höchst from ethylarsenous oxide which
was obtained from the Badische Anilin und Soda Fabrik.
“PREPARATION OF ETHYLARSENOUS OXIDE—The compound was prepared by
treating sodium arsenite with ethyl chloride under pressure. The
resulting sodium salt of ethylarsenic acid was converted into the free
acid and reduced by sulfur dioxide. The ethylarsenous acid formed in
this way lost water and was thereby transformed into ethylarsenous
oxide. The reactions involved are as follows:
C₂H₅Cl + Na₃AsO₃ = C₂H₅AsO₃Na₂ + NaCl
C₂H₅AsO₃Na₂ + 2 HCl = C₂H₅AsO₃H₂ + 2 NaCl
C₂H₅AsO₃H₂ + SO₂ + H₂O = C₂H₅AsO₂H₂ + H₂SO₄
2C₂H₅AsO₂H₂ = (C₂H₅As)₂O + H₂O.
“The ethyl chloride used in the preparation was in part made in this
factory, and in part received from other sources. As ethyl chloride
is an important product used in peace time, it is not, therefore,
essentially a war product and its preparation was not described.
“In preparing the solution of sodium arsenite, one molecular weight
of arsenous oxide was dissolved in a solution containing 8 molecular
weights of sodium hydroxide. The solution of the base was prepared from
a 50 per cent solution of sodium hydroxide to which enough solid alkali
was added to make the solution a 55 per cent one. In one operation 660
kg. of arsenous oxide were used. For 100 parts of arsenous oxide, 130
parts of ethyl chloride were used, this being the theoretical amount of
the latter.
“The reaction was carried out in a steel autoclave of about 300 liters
capacity. The temperature was maintained at between 90° and 95°. The
ethyl chloride was pumped in, in 3 or 4 portions, and the pressure
in the autoclave was kept at from 10 to 15 atmospheres. The several
portions of ethyl chloride were introduced at intervals of about 1½
hrs. During the entire reaction, the contents of the autoclave were
vigorously stirred. After all the ethyl chloride had been added, the
material was stirred from 12 to 16 hrs., at the end of which time
the pressure had fallen to about 6 atmospheres. The excess of ethyl
chloride and the alcohol formed in the reaction were next distilled
off. At this point a sample of the solution was drawn off for testing.
This was done by determining the amount of arsenite present in the
solution. If not more than 20 per cent of sodium arsenite had not
reacted, the preparation was considered satisfactory. Water was then
added to the contents of the autoclave in sufficient amount to dissolve
the solid material. The product was next drawn over into a tank and
neutralized with sulfuric acid. It was then treated with sulfur dioxide
gas until there was an excess of the latter present. The mixture was
then heated to about 70° when the ethylarsenous oxide precipitated as
a heavy oil. This was readily separated and shipped without further
purification. The yield of ethylarsenous oxide, from arsenic oxide, was
from 80 to 82 per cent of a product which contained about 93 per cent
of pure ethylarsenous oxide.
“PREPARATION OF ETHYLDICHLOROARSINE—The compound was prepared by
treating ethylarsenous oxide with hydrochloric acid. The reaction is as
follows:
C₂H₅AsO + 2HCl = C₂H₅AsCl + H₂O.
The operation was carried out in an iron kettle lined with lead, which
was cooled externally by means of water and which was furnished with
a lead covered stirrer. To the kettle, which contained from 500 to
1000 kg. of hydrochloric acid left over from the previous operation,
were added 4000 kg. of ethylarsenous oxide. The gaseous hydrochloric
acid was next led in. The kettle was kept under slightly diminished
pressure in order to assist in the introduction of hydrochloric acid.
The temperature during the reaction must not rise above 95°. When
the hydrochloric acid was no longer absorbed and was contained in
appreciable quantities in the issuing gases, the operation was stopped.
This usually occurred at the end of from one to two days. The product
of the reaction was drawn off by means of a water pump and heated in a
vacuum until drops of oil passed over. The residue was passed over to
a measuring tank and finally to tank-wagons made of iron. The yield of
the product was practically the theoretical.
On account of the volatility of the compound and its poisonous
character, the apparatus in which it was prepared was surrounded by
an octagonal box, the sides of which were fitted with glass windows.
Through this chamber a constant supply of air was drawn. This was led
into a chimney where the poisonous vapors were burned. The gases given
off during the distillation of the product were passed through a water
scrubber.”
“LEWISITE”
The one arsenical which created the most discussion during the War, and
about which many wild stories were circulated, was “Lewisite,” or as
the press called it, “Methyl.” Its discovery and perfection illustrate
the possibilities of research as applied to Chemical Warfare, and
points to the need of a permanent organization to carry on such work
when the pressure of the situation does not demand such immediate
results.
The reaction of ethylene and sulfur chloride, which led to the
preparation of mustard gas, naturally led the organic chemists
to investigate the reaction of this gas and other unsaturated
hydrocarbons, such as acetylene, upon other inorganic chlorides, such
as arsenic, antimony and tin. There was little absorption of the
gas, either at atmospheric or higher pressures, and upon distilling
the reaction product, most of the gas was evolved, showing that no
chemical reaction had taken place. However, when a catalyser, in the
form of aluminium chloride, was added, Capt. Lewis found that there
was a vigorous reaction and that a highly vesicant product was formed.
The possibilities of this compound were immediately recognized and
the greatest secrecy was maintained regarding all the details of
preparation and of the properties of this new product. At the close
of the War, this was considered one of the most valuable of Chemical
Warfare secrets, and therefore publication of the reactions involved
were withheld. Unfortunately or otherwise, the British later decided
to release the material for publication, and details may be found in
an article by Green and Price in the _Journal of the Chemical Society_
for April, 1921. It must be emphasized that the credit for this work
belongs, not to these authors, but to Capt. W. Lee Lewis and the men
who worked with him at the Catholic University branch of the American
University Division (the Research Division of the C. W. S.).
On a laboratory scale, acetylene is bubbled through a mixture of 440
grams of anhydrous arsenic trichloride and 300 grams of anhydrous
aluminium chloride. Absorption is rapid and much heat is developed.
After six hours, about 100 grams of acetylene is absorbed. The reaction
product was dark colored and viscid, and had developed a very powerful
odor, suggestive of pelargoniums. Attempts to distill this product
always led to violent explosions. (It may be stated here that Lewis was
able to perfect a method of distillation and separation of the products
formed, so that pure materials could be obtained, with little or no
danger of explosion.) The English chemists therefore decomposed the
product with ice-cold hydrochloric acid solution of constant boiling
point (this suggestion was the result of work done by Lewis). The
resulting oil was then distilled in a current of vapor obtained from
constant boiling hydrochloric acid and finally fractionated into three
parts.
The first product obtained consist in the addition of one
acetylene to the arsenic trichloride molecule, and, chemically, is
chlorovinyldichloroarsine, CHCl: CH·AsCl₂, a colorless or faintly
yellow liquid, boiling at 93° at a pressure of 26 mm. A small quantity,
even in very dilute solution, applied to the skin causes painful
blistering, its virulence in this respect approaching that of mustard
gas. It is more valuable than mustard gas, however, in that it is
absorbed through the skin, and as stated on page 23, three drops,
placed on the abdomen of a rat, will cause death in from one to three
hours. It is also a very powerful respiratory irritant, the mucous
membrane of the nose being attacked and violent sneezing induced. More
prolonged exposure leads to severe pain in the throat and chest.
The second fraction (β, β′-dichlorodivinylchloroarsine) is a product
resulting from the addition of two acetylene molecules to one arsenic
trichloride, and boils at 130° to 133° at 26 mm. It is much less
powerful as a vesicant than chlorovinyldichloroarsine, but its irritant
properties on the respiratory system are much more intense.
The third fraction, β, β′, β″-trichlorotrivinylarsine, (CHCl: CH)₃As,
is a colorless liquid, boiling at 151° to 155° at 28 mm., which
solidifies at 3° to 4°. It is neither a strong vesicating agent nor a
powerful respiratory irritant. At the same time, its odor is pungent
and most unpleasant and it induces violent sneezing.