Note: Descriptions are shown in the official language in which they were submitted.
~ 5'~7~ C-6324
This invention relates to an improved, integrated method
- for preparing bis-(2-pyridyl-1-oxide) disulfide in high purity
and high yield. More particularly, this invention involves the
preparation of the aforesaid disulfide compound in an integrated,
in-situ method by oxid-izing the alkali metal salt of 2-mercapto-
pyridine, which i~ obtained by oxidation of 2-chloropyridine with
^~ permaleic acid followed by mercaptlzation with a selected sulfide,
wlth hydrogen peroxide using selected pH conditions.
~ The preparation of bis-~2-pyridyl-1-oxide) disulfide (also
- 10 referred to a~ 2,2'-dithiodipyridine-l,l'dioxide) hereinafter
referred to as the disulfide, has been previouæly broadly disclosed
in U.S. Patent 2,742,476 wherein mercaptopyridine-l-oxide is
reacted with an oxidizing agent. U.S. Paten~ 3,759,932 also
generally discloses the preparation of a disulfide componnd using
an in-situ prepsration technique wherein mercaptopyridine is
- not isolated. While these references broadly disclose the pre-
para~ion of the disulfide, problems have arisen when using the
alkali metal salt of 2-mercaptopyridine-1-oxide in an in-situ
technique wherein the alkali metal salt was obtained by oxidizing
2-chloropyridine with permaleic acid to form ~he N-oxide followed
by mercaptization to form the ~alt. When using ~h~s system,
oxidation by the known techn~ques as shown for example in U.S.
Patent 2,742,476 resulted in the formation of undeslred by-
products such as the alk~li metal maleate and al~ali metal fumarate.
This contaminated the desired disulfide product and lowered the
yield. ' ;
It has now bee~ found that when using permaleic acid in the
preparatlon of 2-chloropyridine-1-oxide during the integrated
preparation of the disulfide, the above noted by-product formation
can be avoided and surpri~ingly high yields obtained by operating
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~5,~7~ C-632~ .
the final oxidation in the presence of hydrogen peroxide at
~elected pH condi~ions~ More particularly the oxidation of the
alkali metal salt of 2-mer aptopyridine-l-oxide i8 carried out
at a pH of about 4 to about 5 and preferably from about 4.5 to
about 5. The overall reaction scheme of thts invention i~
illustrated by the following e~uation:
~ . .
~ permaleic acid~ ~ NaSEI ~ ~
~ NJCl ~p~~ N/lSNa
:
H202
~:1s s ~ ~
In the reaction of this invention as illustrated above,
2-chloropyridlne i8 oxidized to ~he N-oxide using permaleic acid .
in accordance with known procedures as dlsclosed for example in
U.S. Patent 2,951,844. The mercaptization of the 2-chloropyridine
N-oxide i8 carried out using an alkali metal sulfide or alkali
metal hydrosulfide in accordance with known procedures as di~closed
in U.S. Patent 2,686,786. The key ~tep in this invention is the
oxidation of the prepared alkali metal salt of 2-mercaptopyridine-
l-oxide u~ing hydrogen peroxide and a reac~ion pH of about 4 to
about 5. By maintaining thë reaction under the6e conditions,
the precipitatlon of undesired impuritle~, primarily derived
from the salts of fumaric acid is avoided and surprisingly high
yields resulted.
In carrying out the reactlon of this invention, the temperature
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~z79z C-632~
may generally be maintained from about 15 to about 35C. ~7ith
about 20 to abo~t 30~C. being preferred. The hydrogen peroxide
concentration may be varied with about 5 to about 30~ in aqueous
solution being generally used. Generally a stoich~ometric ratio
of the alkali metal salt of 2-mercaptopyridine and hydrogen peroxide
of about 2 moles of the mercaptopyridine salt to about 1 mole of
peroxide or a ~light excess of up to about 15% peroxide is used.
It is also generally advisable to agitate the reaction
mixture in the peroxide oxidation step to maintain an effectively
dilute hydrogen peroxide solution.
The pH Df the reac~ion mixture is generally adjusted before
the peroxide oxidation step by using any suitable acidifying
agent such as the non-oxidizing mineral acids such as HCl and the
non-oxidizing organic acids.
While 2-chloropyridine has been shown to be a desired
starting material in the method of this inven~ion, other 2-
halopyridines and substituted halopyridines containing groups
such as lower alkyl and lower alkoxy which do not adversely
affect the reaction may also be used. ~ -
Isolation of the final product after oxidation is obtained
by a standard filtration procedure. ;'
The disulfied compounds prepared in accordance with the
method of this invention have a variety oE known uses, particularly
as antibacterial and antifungal agents in a variety of applications
such as ~o combat agricultural plant diseases ~nd in plastics
and fabrlcs to resist mildew or other fungus a~tack as disclosed
in U.S. Patent 2,742,476.
The following examples are further illustrative of this
invention.
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C-632~
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Example I
A 2-liter, 3-neck flask fitted with a stirrer, thermometer
and addition funnel wa6 charged with 1~866 ~ of 8 reaction mixture
containing the sodium salt of 2-mercaptopyridine-1-oxide. This
reaction mixture had an assay of 7.2% (135 8) of the sodium salt
o 2-mercaptopyridine-1-oxide, 7% sodium chloride and 13-14% total
of sodium maleate and sodium fumarate. Thls mixture was obtained
by oxidi~ing 2-chloropyridine with permaleic acid and then mercapti-
zing wlth NaSH. The pH was then ad~usted to 4.5 with concentrated
hydrochloric acid and the resulting warm solution was cooled to
25C. and 52 ml. of 30% hydrogen peroxide (12% excess over
stoichiometry) in 160 ml. water added dropwise over a 30 mlnute
period with stirring. The reaction was sligh~ly exothermic with
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the temperature rising to approximately 30C. at the end of the ~-
peroxide addition. Stirring of the now precipitated bis-(2-
pyridyl-l-oxide) disulfide product was continued for 2 more hours
to assure completeness of the reaction. The disulfide product
for~ed was collected by filtration and the filter cake washed with
50 ml. water followed by 50 ml of methanol. After air drying,
a total of 112 g (98% yield based on starting sodium salt of
2-mercaptopyridine-1-oxide) of bis-(2-pyridyl-1-oxide) disulfide
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was obtained with a melting point of 200-201C. and an assay of
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8%.
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Example II
Using th~ same procedure as Example I with a reaction
"
mlxture containlng 25.6 g of the sodium salt of 2-mercap~opyridine-
l-oxide 9 14 g of 10% hydrogen peroxide, a pH of 4.0 and a reaction
time of 18 hour~, 17.0 g of the disulfide product was obtained
(79.8% yield ba6ed on sodium salt) having as assay of 97.8%.
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Example III
Using the same procedure as Example I with a reaction mixture
containing 25.6 g of the sodium salt of 2-mercaptopyridine-1-
oxide, 14 g of 10% hydrogen peroxide, a pH of 5.0, a reaction
temperature of 20 ~o 23C. and a reaction time of 18 hours, 19.0
g of the disulfide product was obtained ~89.3% yield based on
sodium salt) and an a~say of 97~7%.
Example IV .
For comparative purposes, the same procedure as Example II
10was followed with a pH of 3Ø A product of 23.5 g was obtalned, .`.
however, it was contaminated with significant quantities of furmaric
acid impurlties.
Example V
For comparative purposes, the same procuedure a3 Example III ~.-
was followed with a p~ of 5.5 and a reaction time of 72 hours. A
product of 10.5 g (b9.3% yield) was obtained. ; ~.
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