Note: Descriptions are shown in the official language in which they were submitted.
The invention relates to the use of 4-nitroso-pyrazoles in microbicidal
agents for protecting industrial materials.
It is known that certain 4-nitroso-pyrazoles, such as, for example,
3,5-dimethyl-1-iso-propyl-4-nitroso-pyrazole, 3,5-dimethyl-1-(4-chloro-phenyl)-
4-nitroso-pyrazole cmd 3,5-dimethyl-1-(4-methyl-phenyl)-4-nitroso-pyrazole,
have fungicidal properties, and in some cases also bactericidal properties,
and can be used in plant protection agents (British 786,753, United States
2,510,724 and Phytopathology 39, 721 - 751 (1949)).
It is known from United States Patent Specification 2,831,866 that
nitroso-pyrazoles are largely suitable for combating pathogenic fungi in
humans and animals.
Microbicidal agents for protecting industrial materials have been
found, which are characterised in that they contain in admixture with a diluent
a microbicidally effective amount of a l-benzyl-3,5-dimethyl-4-nitroso-
pyrazole of the formula
H3C ~ N \
ON ~ (I)
CH3
wherein
Rl represents benzyl which is optionally substituted by halogen,
nitro, Cl to C4-alkyl and/or Cl to C4-alkoxy.
Surprisingly, the microbicidal agents, which are to be used according
to the invention and have the formula (I), for protecting industrial materials
have a considerably more powerful fungicidal and bactericidal action than
known compounds of analogous structure and the same type of action.
Preferred microbicidal agents according to the invention for
-1- ;~
~i
5~;
protecting industrial materials contain l-benzyl-3,5~dimethyl-4-ni~roso-
pyrazole of the formula
113C \ j N \
¦ ~_R2 ~II)
ON / ~=~~~
CH3
wherein
R represents benzyl.
The 4-nitroso-pyrazoles can be prepared by a process in which
hydrazine derivatives of the formula
H2N-NH-R
wherein
Rl has the abovementioned meaning,
or salts thereof, are reacted with isonitroso-acetyl-acetone in an aqueous
dispersion at temperatures between -20 and 50C.
The reaction can be illustrated by the following equation:
c~3
CH3-cO-c-co-cH3 1 2 H2 > \ ~ N
N-OH
ON
\ CH3 OCH3
~ \
~ H2N-NH~
CH ~
;
--2--
~;~
.i
35~ l
The hydrazine deriva-tives are in themselves
known (Methodicum Chimicum 9 Volume 6, page 75-131,
Georg Thieme Verlag, Stuttgart 1974), and they can be }
pr_pared by known processes, for example by reacting
5 hydrazine wi-th acrylonitrile, diazo compounds with bi-- I
sulphites, nitroso compounds with reducing agents, or
halogeno aromatics wi-th hydrazine. It is also
possible for the preparation of the 4-nitroso-pyrazole
to be carried out using, instead of the hydrazine
lO deriva-tives, the precursors, such as 9 for example,
hydrazine and acryloni~rile D wi-thout the hydrazine
derivative being intermediately isolated.
The salts of the hydrazine derivatives can be
prepared by reacting the hydrazine derivative with an
15 acid, for example a mineral acid, such as hydrochloric
acid or sulphuric acid~ ¦
The isonitroso-acetylacetone to be used as a
fur-ther starting component is likewise in itself known
(Wolff~ ~iebigs Annalen der Chemie, 325, 139), and can
20 be prepared from acetylacetone and a nitrite in the pre
sence of an acid.
The reaction temperature can be varied within a
substantial range in the preparation of the 4 nitroso-
pyrazoles. In general, the reaction is carried out
25 in the temperature range ~rom -20 to 50C, preferably
in the temperature range frorn 0 to 30C. The process
is in general carried out under normal pressure.
The starting compounds are generally employed
in approximately equimolar amounts. Between 0.5 and
30 1.5~ preferably between 0.8 and 1.2, mols of isonitroso- !
acetylacetone are employed per mol of hydrazine deriva-
tive~
The process according to the invention can be
carried out, ~or example, as follows:
The hydrazine derivative is dissolved in water
and the solution is cooled with iceO An aqueous
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!l
., ., ... . _~
85~ l
....~..
solution of isoni-trosoacetylacetone is added dropwise
to -this solutionO
The reaction mixture is stirred for 1 to 3 hours~
I~ the products are thereby obtained as crys-tals, they
are isolated by filtration. Otherwise, the mixture
can be worked up by customary methods, for example by
being extracted with an organic solvent which is virtu-
ally immiscible with water9 such as, for example,
diethyl ether, separating of~ the organic extracts and
evaporating these solutions. If appropriate 9 the
products can also be recrystallized,
Xndustrial materials which the 4 nitroso-
pyrazoles according to the invention are to protect from
microbial change and destruction are, for example, non-living
things, such as adhesives, sizes, paper and cardboard, textiles,
le~ther, wood, paintsJ plaster, cooling lubricants and plastic
articles, which can be attacked and decomposed by micro-
organisms~ in the conte~t of materials to be protec~
tedy -there may also be mentioned parts of production
~mits J such as, for example, cooling water circulations
and cooling lubricant circulations, of which the ability
to function can be impaired by micro-organisms.
Micro-organisms which can effect degradation of
or a change in industrial materials are, for example,
bacteria, fungi, yeasts, algae, slimes and viruses.
The 4-nitroso~pyrazoles according to the invention are
preferentially active against bacteria and fungiO
Micro-organisms of the following genera may be
mentioned as examples: Escherichia, such as Escherichia
coli, Pseudomonas, such as Pseudomonas aeruginosa,
Staphylococcus, such as Staphylococcus aureus, Alter- ¦
naria, such as Alternaria tenuis~ Aspergillus, such as
Aspergillus niger, Chaetomonium J such as Chaetomonium
globosum, Coniophora, such as Coniophora cerebella,
Lentinus, such as Lentinus tigrinusS Penicillium, such
as Penicillium glaucum, Polyporus 7 such as Polyporus
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_
S~ I
0~3 ~
versicolor, Pullularia, such as Pullularia pullulans,
Sclerophoma, such as Scle.ophoma pityophila and Tricho
derma, such as Trichoderma viride.
The 4-nitroso-pyrazoles according to the inven~
tion can be converted into the customary formulations,
such as solutions, emulsions~ suspensions, powders~
pastes and granules, depending on their field of appli-
cation These formulations can be prepared in a
manner which is in itself kno~m, for example by mixing
the active co~pounds with an extender7 with liquid sol
vents and/or solid carriers, optionally with the use
of surface-active agents, such as emulsifiers and/or
dispersing agents; in the case of the use of water e~ter.ders
for example, organic solvents can op-tionally be used as
auxiliary solvents.
The organic solvents for the active compo~nds
can be, for example, alcohols, such as lower aliphatic
a]cohols~ preferably ethanol or isopropanol, or benzyl
alcohol 7 ~ketones, such as acetone or ~ethyl ethyl
ketone, liquid hydrocarbons, such as benzine fractions,
or chlorinated hydrocarbons, such as 1,2-dichloroethaneO
The concentration in which the 4-nitroso-
pyra~oles according to the invention are used depend on
the nature and occurrence Oî the micro-organisms to be
combated, as well as on the composition of the material
to be protectedO The optimu~ a~ounts employed can
be determined by a test series~ In general, the use
concentrations are in the range from 0.001 to 5% by
weight, preferably from 0.05 to 0.5% by weight, relative
30 to the material -to be pro-tected~ 1
The new active compounds according to the inven- i
tion can also be present as mixtures with other kno~
active compoundsO The following active compounds may
be mentioned as examples: benzimidazolyl-meihyl carbam-
ate, tetramethyl-thiuram disulphide, N~fluorodichloro~
methy1thio-phthalimide and N,N-dimethyl-M'-phenyl-(N'
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f~ 56
fluorodichloromethylthio)-sulphamide, compounds which split off formaldehyde,
such as hemiformals, oxazolidines, hexahydro-s-triazines and N-me~hylolamides,
and phenol derivatives, such as p-chloro-m-cresol, 2--phenylphenol and
(2,2'-dihydroxy-5,5'-dichloro)-diphenylmethane.
A) Preparation Exa~les
Example 1 CH3 N
,~N-CH2--~
ON
c~3
12.9 g (0.1 mol) of isonitroso-acetylacetone in 100 ml of water are
added dropwise to a solution of 19.5 g (0.1 mol) of benzyl hydraæine dihydro-
chloride in 200 ml of water at O ~ 5CJ whilst stirring vigorously. The
reaction mixture is subsequently stirred at room temperature for 2 hours and
is extracted twice with 100 ml of ether each time, and the combined ether
extracts are then evaporated. 18 g (84% of theory) of 3,5-dimethyl-1-benæyl-
4-nitroso-pyrazole are obtained in the form of blue-green crystals.
After recrystallisation of the crystals from benzene/ligroin, the
pure substance, with a melting point of 64C~ is obtained.
Example 2
~ \N CH
ON
CH3
An aqueous solution of benzyl hydrazine (prepared from 19.4 g
(0.1 mol) of benzyl hydrazine dihydrochloride, 150 ml of water and 16.8 g
(0.2 mol) of sodium bicarbonate) is added dropwise to a vigorously stirred
, -6-
s~
solution of 12.9 g (0.1 mol) of isonitrosoacetylacetone in 100 ml of water at
0C in the course of 2 hours. After about 1/10 of the benzyl hydrazine solution
has been added, a few seed crystals of 3,5-dimethyl-1-benzyl-4-nitroso-pyrazole
are added. The mixture is subsequently stirred at a temperature of 0 - 20C
for 5 hours. The blue, crystalline precipitate is then filtered off, washed
with cold water and dried in air.
20 g (93% of theory) of 3,5-dimethyl-1-benzyl-4-nitroso-pyrazole are
obtained in the form of blue crystals of melting point 64 C.
_ Use Examples
Example 3
To detect the activity against fungi, the minimum inhibitory
concentrations ~MIC) of active compaunds are determined:
Active compounds in concentrations of 0.5 mg/l to 5,000 mg/l are
added to an agar, which is prepared from beer wort and peptone. After the
agar has solidified, it is contaminated with pure cultures of test organisms
listed in the table. After keeping the agar at 28C and at a relative
atmospheric humidity of 60 to 70% for two weeks, the MIC is determined. The
MIC is the lowest concentration of active compound at which no growth of the
species of microbe used takes place at all, and is given in the following table.
Table I: Data for the MIC values in mg/l for the action of the
active compounds below on fungi
Active compound A: 3,5-Dimethyl-l-benzyl-4-nitroso-pyrazole (according to
the invention)
Active compound B: 3,5-Dimethyl-1-(2-methoxyphenyl)-4-nitroso-pyrazole
(comparison)
Active compound C: 3,5-Dimethyl-l-isopropyl-4-nitroso-pyrazole (comparison)
Test fungi Active compounds
A B C
Alternaria tenuis - 10.0 15.0
Aspergillus niger 5 10.0 10.0
Aspergillus terreus 20.0 - -
Chaetomium globosum 2.030.0 50.0
Coniophora cerebella - 1.0
Lentinus tigrinus - 3.5
Penicillium glaucum 2.0 10.0 50.0
Polyporus versicolor - 7.5
~Illularia pullulans < 1.0 3.5
Sclerophoma pityophila - 2.0
Trichoderma viride - 30.0 50.0
Rhizopus nigricans 2.0 - -
Example 4 (Preservation of a cooling lubricant)
0.2 % of 3,5-dimethyl-1-benzyl-4-nitroso-pyrazole is added to a
cooling lubricant based on mineral oil and the mixture is then diluted to 5%
strength with water, so that the use dilution contains 0.01% of active
compound according to the invention.
s~ l
\ q
The use dilution is contaminated wi-th a large
quantity of microbes (bac-teria and moulds), which
originate from a microbially spoiled cooling lubricant,
each day for 12 weeks. To monitor the preserving
action of the microbicide, the number of germs is deter-
mined 24 hours after each con-tamination,
Result: Even after 12 weeks~ the preserved
cooling lubricant i.s still free from germs; in con-
trast~ a cooling lubricant which has not been preserved
but has been treated in the same manner already contains
about 10 germs/ml after the first contamination? and
shows a clear indication of microbial decomposition
after 12 weeks.
I.e A ZO 4Zz~
