Hydrazinium Hydrazinesulfinates
Year:
Abstract:
This invention relates to the reaction of organic substituted hydrazines with sulfur dioxide. In one specific aspect, it relates to a novel process for making organic substituted hydrazinium hydrazinesulfinates. In yet another aspect, it relates to the composition of matter produced thereby.
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United States Patent Cffice
2,888,483
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2,888,483
HYDRAZINIUM HYDRAZINESULFINATES
Bernard Rudner, Pittsburgh, Pa., and Marguerite E. i
Brooks, Baltimore, Md., assignors to W. R. Grace 8:
_Co., New York, N.Y., a corporation of Connecticut
No Drawing. Application September '16, 1958
Serial No. 761,294
13 Claims. (Cl. 260—501)
Thisinvention relates to the reaction of organic sub-
stituted" _hydrazines.with sulfur dioxide. In one specific
aspect, itrelates to a novel process for making organic
substituted hydrazinium‘hydrazinesulfinates. In yet an-
other aspect, it relates to the novel compositions of matter
produced thereby. , ’ '
The reaction of sulfur compounds with compounds con- '
taining two adjacent nitrogen atoms is not new to the art.
The useful and well known sulfonhydrazides are made
by the reaction of sulfonyl halides on hydrazine or sub-
stituted_hydrazines. Phenylhydrazine has been prepared
for many years by the reduction of phenyldiazonium salts
with sulfur dioxide usually in the form of the alkali metal
sulfite. Hydrazine itself is known to interact with sulfur
dioxide toform an .unusual compound containing three
hydrazines to two sulfurdioxides. We have discovered,
however, that the reaction of sulfur dioxide with organic
substituted hydrazines unexpectedly gives the novel or-
ganic substituted hydrazinium hydrazinesulfinates.
It is, therefore, an object of the present invention to pro-
vide a new generic class of organic compounds, heretofore
unavailable, useful as bactericides, fungicides and nema-
tocides as well as for a variety of other purposes.
In accordance with the present invention, we have dis-
covered a novel process for the synthesis of organic sub-
stituted hydrazinium hydrazinesulfinates having the gen-
eral formula (RR’NHNH2) (RR’NNHSOg). In this for-
mula R is a monovalent radical selected from the group
consisting of lower alkyl, hydroxy lower alkyl, phenyl
and benzyl. R’ is a monovalent radical selected from the
group consisting of hydrogen, lower alkyl and benzyl. It
is apparent that our novel compounds are salts containing
the 2- or _2,2v-substituted hydrazinium cation
(RR’NHNH2)+
and the corresponding 2- or 2,2-substituted hydrazine-
sulfinate anion (RR’NNHSO2)".
A brief discussion of the chemical and physical prop-
erties of these compounds will be required in order to
better understand the method used for their production.
Usually our novel compounds are insoluble in hydrocar-
bon solvents and moderately polar organic solvents. They
are soluble in water and highly polar organic solvents.
On heating, the compounds dissolve in less polar solvents
but heating ‘above 50° C. in any solvent may cause decom-
position" of the salt. Naturally the exact temperature
at which decomposition becomes undesirable depends’ on
the given salt and the solvent used. It is important to note
that certain of our compounds, when in‘ solution or wet
with solvent, are particularly susceptible to air oxidation.
When such a product is collected by filtration using suction
to aid in "the filtration and to promote drying or removal '
of solvent from the filter cake, oxidation of the product
will result as air is pulled through the wet cake. When
this occurs, suction-filtration should be done under a
rubber’ dam or in -an inert atmosphere. - g
Since -the reaction of organic substituted hydrazines
with sulfur dioxide is highly exothermic, excess substituted
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hydrazine must be present or preferably an inert solvent
should be used. By inert it is meant that the solvent
should be unreactive to the products or reactants of our ‘
invention during the course of the reaction process. Suit-
able solvents are aliphatic and aromatic hydrocarbons,
chlorinated hydrocarbons,» lower aliphatic alcohols, etc.
"Typical solvents used were xylene, trichloroethylene,
chloroform, isopropyl alcohol and various petroleum
hydrocarbon fractions.
illustrative of the types of solvents that may be used in
our invention and are not meant to be limiting. ‘Any _,
unreactive or non-interfering solvent comes within the
scope of our invention.
usually limited to one in which the reactant organic sub-
stituted hydrazine is soluble. A further choice of solvent
is made depending on whether it is desirable to isolate the
product as a solution (especially when it is particularly '
susceptible to decomposition‘ in air) or to collect it by .
In additionto 1
the use of a solvent, it is necessary to provide means for
separation (liquid) or filtration (solid).
externally cooling the reaction vessel. As mentioned and
discussed previously, the reaction is highly exothermic '
and the product decomposes on heating in solution much .
above 50° C. From the above remarks it is also obvious
that efficient operation of our process on a larger scale
requires a means for adequate stirring of the reaction
mixture at all stages of the process. ’I‘his_becomes par-
ticularly important at the’ latter stages of the process‘ when
the reaction mixture has become thickened with product.
Preferably our novel process is operated as follows: The
selected organic substituted hydrazine is dissolved in a»
solvent in which the resultant hydrazinium hydrazinesul-
finate will be insoluble. The stirred contents of the
reaction vessel are chilled by external cooling and ex—‘
cess gaseous sulfur dioxide (from a cylinder protected
by a trap) is passed into the reaction mixture. It is im- V
perative to keep the temperature of the reaction mixture
below 50° C. to avoid decomposition of the product and
preferably below 30° C. to get a purer, lighter colored
product. Temperature control is accomplished by the
aforementioned cooling bath and by adjusting the rate of
flow of sulfur dioxide into the reaction mixture. When
the temperature starts rising, the flow rate is lessened
to diminish the amount of heat formed by the exothermic
reaction. The addition of sulfur dioxide is stopped when
the reaction mixture becomes _too thick for eflicient stir-
ring and/or further absorption of the gas ceases. The
product is collected by filtration, using the precautions
previously discussed, and dried in vacuo.
The novel compositions of our invention have been
found useful as polymerization initiators and surprisingly
as rodent repellants. Our hydrazinium hydrazine sul-
finates have been tested and found useful as bactericides,
fungicides and nematocides. Microbiological activity
was tested-by means of the Oxford Cup Method, The
cups were placed on innoculated culture media, filled with “
buffered test solution and the whole incubated for the re- ’
In this method the zone of inhibition-of‘
microbial growth is a measure of the bacteriostatic or '
fungistatic activity of the given compound against the‘
quired time.
selected test organism. Using the appropriate culture
media, tests were made of bacteriostatic activity against
five representative bacterial species» and of fungistatic
activity against three selected species of fungi as described _
below:
FIVE TEST BACTERIA
(1) Micrococcus pyogenes—-can enter broken skin to
cause infection also may cause food poisoning. .
(2) Pseudomonas aerogz'nosa—a denitrifying organism ‘
which causes decay of protein.
(3) Serratia marcescens——a water-living saprophytic
Patented May—26, 1959
These remarks are meant to be -
The choice of the solvent is s
2,888,488
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organism which reduces nitrates, liquefies blood serum
and coagulates and digests milk.
(4) Escherichia colz'—commonly found in the intes-
tinal canal.
(5) Klebsiella pneumom'ae—can cause infection of
respiratory and genito-urinary tracts.
THREE TEST FUNGI
(1) Candida albz'cans—has been known to cause acute
fatal moniliases (lesions of the skin, mucous membranes
and internal organs).
(2) Microsporum gypseum-—causes skin diseases such
as ring worm and barber’s itch.
(3) Clzaetomium globosum—causes deterioration of
cellulosic materials.
The scope and utility of my invention is further illus-
trated by the following examples:
Example 1
Dry sulfur dioxide gas was passed for 2 hoursthrough
a chilled solution of 20 g. of 1,1-dimethylhydrazine in
200 ml. of chloroform. A gelatinous supernatant layer
appeared which was allowed to coagulate overnight be-
fore being collected by filtration under a rubber dam.
On drying in a vacuum desiccator, the colorless solid
appeared as long needles partially subliming at 28° C.,
melting 34—37° C. and evolving gas ca. 90° C. There
resulted 7.7 g. of the product, 2,2-dimethylhydrazinium
2,2-dimethylhydrazinesulfinate.
Example II
Dry sulfur dioxide gas was passed for 2 hours through
a chilled solution of 20 g. of rnethylhydrazine in 200
ml. of chloroform as in Example I. The reaction mix-
ture separated into two liquid phases. The upper yellow
layer was essentially 2-methylhydrazinium 2-methylhy-
drazinesulfinate unstable in the presence of air. When
the same procedure was repeated using isopropyl alcohol
as the solvent, a stable solution of the product was ob-
tained.
Example III
Dry sulfur dioxide gas was passed for 2 hours through a
chilled solution of 36 g. of phenylhydrazine in 200 ml.
of trichloroethylene. A yellow solid formed immediately
and on further standing additional solid precipitated. The
crude product decomposing ca. 210° C. was collected in
good yield by filtration under a rubber darn.
Example 1 V
Eighty grams of 1,1-dimethylhydrazine dissolved in
300 ml, of trichloroethylene was thoroughly chilled in
an ice bath and kept cool during the 10 hour passage of
sulfur dioxide into the reaction mixture. Working up
the resultant 2,2-dimethylhydraziniurn 2,2—dimethylhy-
drazinesulfinate according to the procedure of Example
I, gave 134.6 g. of product.
Example V
Dry sulfur dioxide gas was bubbled through a solution
of 35 g. of 2-hydroxyethylhydrazine in 1000 ml. of iso-
propyl alcohol for 30 minutes. Evaporation of the sol-
vent left a yellow viscous liquid which contained some
white crystalline solid. The residue was dissolved in
methyl alcohol and added with stirring to an excess of
ether forming two liquid layers. The yellow product
layer was separated and dried to give 55 g. of a light
yellow viscous liquid. The product, 2-(2-hydroxyethyl)
hydrazinium 2-(2-hydroxyethyl)hydrazinesulfinate, de-
composed at 40° C. and began to char ca. 100° C.; its
aqueous solutions had a pH of 5.35.
Example VI
A flask containing 324 g. of phenylhydrazine dissolved
in 1838 g. of xylene was kept in a water bath at about
20° C. After the addition with stirring of 338 g. of
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sulfur dioxide over a period of 97 minutes, the resultant
slurry was allowed to stand several hours before being
filtered under a rubber dam. (When an attempt was
made to dry the filter cake by pulling air through it, the
cake became very hot, began to smoke and started local-
ized decomposition with pronounced charting.) On
drying there was obtained 290 g. of 2-phenylhydraziniu.m
2-phenylhydrazinesulfinate as a pale yellow solid which
decomposed ca. 225 ° C. At room temperature, the
product was insoluble in ether, chloroform, water, lower
alcohols, ethyl acetate, benzene’ and xylene; it was solu-
ble in methyl alcohol, ethyl acetate and chloroform at
50° C. but at higher temperatures decomposition be-
came extensive. The product analyzed 51.96% C, 6.28%
H and 19.21% N as compared to the calculated values
of 51.41, 5.75 and 19.99% respectively.
Example VII
Using the same general procedure as in die previous
example, but without any stirring, 541 g. of phenylh'y-
drazine in 1620 g. of xylene was treated with 282 g.
of sulfur dioxide over a period of 71 minutes. A yield
of 392 g. of dried product was obtained. As with the
filtrate of the previous example, more product could
be isolated by evaporation of the filtrate. Here it was
found preferable to recycle the filtrate by recharging it
with another 541 g. of phenylhydrazine and 306 g. of
xylene. The passage of 262 g. of sulfur dioxide over a
period of 55 minutes gave 483 g. of product after fil-
tration and drying. .
Example VIII
2-phenylhydrazinium 2-phenylhydrazinesulfinate, a
typical compound of this invention, was tested in vitro
by the Oxford cup method for bacteriostatic activity.
Phenol and Zephiran (a refined benzalkonium chloride)
were used as controls. In each experiment, three stain-
less steel Oxford cups (10 mm. in diameter) were
placed equidistant on the innoculated culture medium
in a Petri dish and the cups filled approximately three-
quarters full with test solution containing 0.2% of the
substance to be tested. After incubation for the appro-
priate period, the plates were examined and the diameter
of the zone of the inhibition of microbial growth sur-
rounding each cup measured. Obviously, the larger the
zone of inhibition, the more effective are the bacterio-
static properties of the compound tested. Because of the
size of the Oxford cups use, 10 mm. is considered to
represent zero inhibition.
ZONE OF INHIBITION >AT pH'=3.ti
Organism Media Zephiran Phenol Sulfinate
1. M. pyogenes _____________ -_ A 21 10 14
2. P. aeruginosa_- - A 10 10 12
3. P. rzerugi7Los:z_.__ - B 10 10 10
4. S. mr1r4zscens__ A 14 10 13
5. E. ooh ....... -_ A 18 10 16
6. K. pneumaniae B 11 10 14
7. K. pneumoniae A 17 10 23
_
ZONE or INHrBI'rioN Afr pH=7.o
Sulfzlnste
Organism Media Zephiran Phenol
1. M. pyogenes ............. _- A 21 10 16
2. P. aeruginosa-- A 10 10 ¢.
3. P. aeruginosa B 10 10 14
4. S. mamscens A 14 10 16
5. E. coli _____ _. A 17 10 L0
6. K. pneumom'ae._ B 12 10 15-‘
7. K. pneumoniae .......... -- A 17 10 30
Media. A: nutrient agar.
Media B: nutrient agar + 10% horse serum.
Example IX
Using the procedure of the previous example, the in
vitro fungistatic activity of 2-phenylhydrazinium 2-
(./‘‘.,,,...,,§
2,338,483
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phenylhydrazinesulfinate was tested by the Oxford cup
method against Phenol and Zephiran as controls.
ZONE OF INHIBITION AT pH=3.0
Organism Media Zephiran Phenol Sulfumtc
1. C’. albicans .............. -. A 15 10 27
2. C’. albicans .............. _- B 13 11 212
3. M. gypscum _____________ -- A 38 10 47
4. C’. glabosum ............. -- C 28 11 2-1
ZONE OF INHIBITION AT pH=7.0
Organism Media Zephiran Phenol Sulfmate
1 C albicans ______________ -. A 17 10 32
2. C’ albicans__ B 12 10 24
3. M. 91/pseum_-- A 35 10 2:.
4. O. qlobosum... C 23 12 48
Media A: Babourauds dextrose agar.
Media B: Babourauds dextrose agar + 10% horse serum.
Media 0: Potato agar.
We claim:
1. Chemical compounds having the general formula
(RR’NHNH2) (RR’NNHSO2) wherein R is a monovalent
radical selected from the group consisting of lower alkyl,
hydroxy lower alkyl, phenyl and benzyl and R’ is a mono-
valent radical selected from the group consisting of lower
alkyl hydroxy lower alkyl, phenyl and benzyl and R’ is
a monovalent radical selected from the group consisting
of hydrogen, lower alkyl and benzyl.
2. Compounds according to claim 1 wherein R is hy-
droxy lower alkyl and R’ is hydrogen.
3. Compounds according to claim 1 wherein R and R’
are lower alkyl.
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4. Compounds according to claim 1 wherein R is lower
alkyl and R’ is hydrogen.
5. 2,2-dimethylhydrazinium 2,2-dimethylhydrazinesul-
finate.
6. 2-methylhydrazinium 2-methylhydrazinesulfinate.
7. 2-(2-hydroxyethyl)hydrazinium 2-(2-hydroxyethyl)
hydrazinesulfinate.
8. 2-phenylhydrazinium 2-phenylhydrazinesulfinate.
9. A method of making organic substituted hydrazini-
um hydrazinesulflnates having the general formula
(RBJNHNH2) (RR’NNHSO2) wherein R is a monovalent
radical selected from the group consisting of lower
alkyl, hydroxy lower alkyl, phenyl and benzyl and R’ is
a monovalent radical selected from the group consisting
of hydrogen, lower alkyl and benzyl which comprises pro-
viding a solution of an organic substituted hydrazine hav-
ing the formula RR’NNH2 wherein R and R’ are defined
as above in an unreactive solvent, maintaining at all
times a temperature below 50° C., contacting said solu-
tion with gaseous sulfur dioxide and recovering said
hydrazinesulfinate therein formed from the reaction mix-
ture.
10. A method according to claim 9 wherein R is hy-
droxy lower alkyl and R’ is hydrogen.
11. A method according to claim 9 wherein R and R’
are lower alkyl.
12. A method according to claim 9 wherein R is phenyl
and R’ is hydrogen.
13. A method according to claim 9 wherein R is lower
39 alkyl and R’ is hydrogen.
References Cited in the file of this patent
Ephraim et al.: Ber. 44, 386-394 (1911).
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