7,7-Dichloro-bicycloheptane imide compounds and their use as biocides

Novel compounds having the formula ##STR1## in which R is thio(halo-lower alkyl) or 3,4-dichlorophenyl, having bactericidal and/or fungicidal properties.

This invention relates to novel compounds having the formula 
##STR2## 
in which R is thio(halo-lower alkyl) or 3,4-dichlorophenyl. As will be 
seen from the data hereinafter, these compounds possess activity against 
certain fungi and bacteria. 
By the term "lower alkyl" is meant saturated acyclic substituents of this 
type having from 1 to 4 carbon atoms. The term "halo" is intended to 
include fluoro, chloro, bromo and iodo and may include one or several 
types of halogens substituted on a particular lower alkyl moiety. 
Preferred embodiments of this substituent are fluoro and/or chloro. 
A general method of preparation of the compounds of the present invention 
is as follows. 
A diester of a tetrahydrophthalic acid is condensed with dichlorocarbene to 
form a bicyclo[4.1.0] heptane. The ester group can then be hydrolyzed to 
the diacid which can then be converted to the anhydride by treating with a 
conventional dehydrating agent, for example acetyl chloride. The anhydride 
is then converted to an imide by reaction with a source of ammonia, such 
as urea. The compounds of this invention can be prepared by condensing the 
imide with a sulfenyl chloride in the presence of a base, for instance, 
triethylamine.

The following is a representative example of a compound of this invention. 
Preparation of N-(trichloromethyl-thio)bicyclo 
[4.1.0]heptane-7,7-dichloro-3,4-dicarboxylic acid imide (Compound No. 1 
herein). 
(a) There were placed in a flask 126 grams of 4,5-dicarboethoxy 
cyclohexene, 100 milliliters of chloroform and 5 grams of tetrabutyl 
phosphonium chloride. To the resulting solution there was added 110 
milliliters of a 50% aqueous solution of sodium hydroxide. The addition 
was carried out over a three-hour period; the mixture was then stirred for 
an additional three hours. There were then added 150 milliliters of water 
and 80 milliliters of a 50% aqueous solution of sodium hydroxide; the 
mixture was stirred for several more hours. Water was added to dissolve 
the solids and the solution was washed once with chloroform. The aqueous 
layer was then acidified with concentrated hydrochloric acid and extracted 
with methylene chloride. The methylene chloride was dried and evaporated 
to yield 62 grams of a tan solid, identified as 
bicyclo[4.1.0]heptane-7,7-dichloro-3,4-dicarboxylic acid. 
(b) In a flask were placed 5.5 grams of the dicarboxylic acid prepared in 
step (a) above and 10 milliliters of acetyl chloride. The solution was 
heated to reflux for 15 minutes. The reaction mixture was then evaporated 
at a high vacuum to yield 4.7 grams of a tan solid identified as the 
anhydride of the acid prepared in step (a). 
(c) In a flask were placed 4.7 grams of the anhydride prepared in step (b) 
above, 1.2 grams of urea and 10 milliliters of acetic acid. The mixture 
was refluxed for 11/2 hours, then allowed to cool. Methylene chloride was 
then added and the organic layer washed with water and then eith a 5% 
aqueous solution of potassium carbonate. The organic layer was then dried 
and the solvent evaporated to yield 3 grams of a tan solid, identified as 
the imide of the carboxylic acid in step (a). 
(d) In a flask were placed 2.4 grams of the imide prepared in step (c) 
above, 1.1 grams of triethylamine and 10 milliliters of methylene 
chloride. To this solution was added 1.9 grams of 
perchloromethylmercaptan, dissolved in 5 milliliters of methylene 
chloride. The reaction mixture was then stirred for several hours, 
following which 100 milliliters of methylene chloride was added and the 
solution washed with water. The organic layer was separated, dried and the 
solvent stripped to yield 3.8 grams of a tan solid, melting point 
140.degree.-155.degree. C. identified as 
N-(trichloromethylthio)bicyclo[4.1.0]heptane-7,7-dichloro-3,4-dicarboxylic 
acid imide. 
The following Table I contains representative examples of compounds of the 
present invention. 
Identification of the compounds produced in steps (a)-(d) above and in 
Table I was performed by infrared, nuclear magnetic resonance and mass 
spectroscopic techniques. 
TABLE I 
______________________________________ 
##STR3## 
Compound 
No. R m.p., .degree.C. 
______________________________________ 
1 SCCL.sub.3 140-155 
2 SCCl.sub.2 CCl.sub.2 H 
161-164 
##STR4## (semi-solid) 
4 SCCl.sub.2 CCl.sub.2 F 
(crude solid) 
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Fungicidal and Bactericidal Evaluation 
The compounds in Table I above were tested for fungicidal and bactericidal 
activity by the following procedures. 
In Vitro Vial Tests 
Tubes of sterilized nutrient and malt extract broth were prepared. Aliquots 
of the toxicant, dissolved in an appropriate solvent, were injected 
through the stopper, into the broth, to provide concentrations ranging 
from 50 ppm downward. The test organisms consisted of two fungi, 
Aspergillus niger (A.n.) van Tieghem and Penicillium italicum (P.i.) 
Wehmer, and three bacteria, Escherichia coli (E.c.) Migula, Staphylococcus 
aureus (S.a.) Rosenbach and Erwinia amylovora (E.a.), (Burill) Sinslow, et 
al. Three drops of a spore suspension of each of the fungi were injected 
into the tubes of malt broth and three drops of the bacteria were injected 
into the nutrient broth. One week later the growth of each organism was 
observed and effectiveness of the chemical was recorded as the lowest 
concentration in ppm which provided 100% inhibition of growth as compared 
to untreated inoculated tubes. 
The results of these tests are found in Table II. 
TABLE II 
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(Values in ppm) 
Compound 
No. A.n. P.i. E.c. S.a. E.a. 
______________________________________ 
1 5 5 &gt;50 5 10 
2 1 1 &gt;50 10 &gt;50 
3 &gt;50 &gt;50 &gt;50 0.5 &gt;50 
4 5 1 &gt;50 25 25 
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Foliar Preventative Sprays 
Bean Rust 
The chemicals were dissolved in an appropriate solvent and diluted with 
water containing several drops of a wetting agent. Test concentrations, 
ranging from 1000 ppm downward, were sprayed to run-off on the primary 
leaves of pinto beans (Phaseolus vulgaris L. ). After the leaves were 
dried, they were inoculated with a water suspension of spores of the bean 
rust fungus (Uromyces phaseoli Arthur) and the plants were placed in an 
environment of 100% humidity for 24 hours. The plants were then removed 
from the humidity chamber and held until disease pustules appeared on the 
leaves. Effectiveness was recorded as the lowest concentration, in ppm, 
which provided 75% or greater reduction in pustule formation as compared 
to untreated, inoculated plants. 
Bean Powdery Mildew 
Test chemicals were prepared and applied in the same manner as for the bean 
rust test. After the plants were dry, the leaves were dusted with spores 
of the powdery mildew fungus (Erysiphe polygoni De Candolle) and the 
plants were retained in the greenhouse until the fungal growth appeared on 
the leaf surface. Effectiveness was recorded as the lowest concentration, 
in ppm, which provided 75% or greater reduction in mycelial growth on the 
leaf furface as compared to untreated, inoculated plants. 
Tomato Early Blight 
Test chemicals were prepared and applied in the same manner as the bean 
rust and powdery mildew tests except that 4-week old tomato (Lycopersicon 
esculentum) plants were utilized as the host plant. When the leaves were 
dry, they were inoculated with a water suspension of spores of the early 
blight fungus (Alternaria solani Ellis and Martin) and placed in an 
environment of 100% humidity for 48 hours. The plants were then removed 
from the humidity chamber and held until disease lesions appeared on the 
leaves. Effectiveness was recorded as the lowest concentration, in ppm, 
which provided 75% or greater reduction in the number of lesions formed as 
compared to untreated, inoculated plants. 
Bluegrass leaf spot 
The test chemicals were dissolved in an appropriate solvent and further 
diluted with a 50:50 acetone:water solution. "Marion" Kentucky Bluegrass 
plants (Poa pratensis L.), approximately four weeks old, were sprayed to 
the point of run-off with the test solutions. Test concentrations ranged 
from 1000 ppm downwards. After the leaves dried, they were inoculated with 
a water suspension of Helminthosperium sativum Tammel and held in a 
greenhouse at 27.degree. C. until disease lesions appeared on the leaves. 
Effectiveness was recorded as the lowest concentration in ppm which 
provided 75% or greater reduction in the number of lesions as compared to 
untreated inoculated plants. 
Foliar Eradicative Sprays 
Bean Rust 
Untreated bean plants were inoculated with spores of the bean rust fungus 
and placed in an environment of 100% humidity for 24 hours. They were then 
removed from the humidity chamber and held in the greenhouse for two days 
to allow the disease to become established. The test chemicals were then 
prepared and applied in the same manner as in the preventative spray 
tests. Eradicative effectiveness was recorded as the lowest concentration, 
in ppm, which provided 75% or greater reduction in pustule formation as 
compared to untreated inoculated plants. 
Bean Powdery Mildew 
Untreated pinto bean plants were dusted with spores of the powdery mildew 
fungus and maintained in the greenhouse until mycelial growth appeared on 
the leaf surface. Test chemicals were then prepared and applied in the 
same manner as for the preventative spray test. Four days later, the 
leaves were examined for inhibition of further mycelial growth. 
Eradicative effectiveness was recorded as the lowest concentration, in 
ppm, which provided 75% or greater reduction in mycelial growth on the 
leaf surface as compared to untreated inoculated plants. 
Tube Systemic Test 
Bean Rust 
The chemicals were dissolved in an appropriate solvent and diluted with tap 
water to a series of descending concentrations beginning at 50 ppm. Sixty 
milliliters of each concentration was placed in a test tube. A pinto bean 
plant was placed in each tube and supported with a piece of cotton so that 
only the roots and lower stem were in contact with the test solution. 
Forty-eight hours later the bean leaves were inoculated with a water 
suspension of spores of the bean rust fungus and placed in an environment 
with 100% humidity for 24 hours. The plants were then removed from the 
humidity chamber and maintained in the greenhouse until the disease 
pustules appeared on the leaves. Effectiveness was recorded as the lowest 
concentration, in ppm, which provided 75% or greater reduction in pustule 
formation as compared to untreated, inoculated plants. 
Bean Powdery Mildew 
Test chemicals were prepared and applied in the same manner as for the bean 
rust systemic test. After two days, the leaves were dusted with spores of 
the powdery mildew fungus and maintained in the greenhouse until mycelial 
growth appeared on the leaf surfaces. Effectiveness was recorded as the 
lowest concentration, in ppm, which provided 75% or greater reduction in 
mycelial growth on the leaf surface as compared to untreated, inoculated 
plants. 
The results of the various evaluations are contained in Tables IIIA-IIIC 
which follow: 
TABLE IIIA 
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Foliar Preventative Tests (ppm) 
Compound Bean Powdery Tomato Leaf 
No. Rust Mildew Blight Spot 
______________________________________ 
1 500 100 500 1000 
2 100 &gt;1000 &gt;1000 500 
3 &gt;1000 &gt;1000 -- -- 
4 100 &gt;1000 500 500 
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TABLE III B 
______________________________________ 
Foliar Eradicative Tests (ppm) 
Compound Bean Powdery 
No. Rust Mildew 
______________________________________ 
1 -- 1000 
2 &gt;1000 -- 
3 -- -- 
4 &gt;1000 -- 
______________________________________ 
TABLE III C 
______________________________________ 
Systemic Tests (ppm) 
Compound Bean Powdery 
No. Rust Mildew 
______________________________________ 
1 &gt;50 &gt;50 
2 &gt;50 -- 
3 &gt;50 -- 
4 &gt;50 -- 
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The compounds of this invention are generally embodied into a form suitable 
for convenient application. For example, the compounds can be embodied 
into pesticidal compositions which are provided in the form of emulsions, 
suspensions, solutions, dusts and aerosol sprays. In general, such 
compositions will contain, in addition to the active compound, the 
adjuvants which are normally found in pesticide preparations. In these 
compositions, the active compounds of this invention can be employed as 
the sole pesticide component or they can be used in admixture with other 
compounds having similar utility. The pesticide compositions of this 
invention can contain, as adjuvants, organic solvents, such as sesame oil, 
xylene range solvents, heavy petroleum, etc.; water; emulsifying agents; 
surface active agents; talc; pyrophyllite, diatomite; gypsum; clays, 
propellants such as dichlorodifluoromethane, etc. If desired, however, the 
active compounds can be applied directly to feedstuffs, seeds, etc., upon 
which the pests feed. When applied in such a manner, it will be 
advantageous to use a compound which is not volatile. In connection with 
the activity of the presently disclosed pesticidal compounds, it should be 
fully understood that it is not necessary that they be active as such. The 
purposes of this invention will be fully served if the compound is 
rendered active by external influences, such as by light, or by some 
physiological action which occurs when the compound is ingested into the 
body of the pest. 
The precise manner in which the pesticidal compositions of this invention 
are used in any particular instance will be readily apparent to a person 
skilled in the art. Generally, the active pesticide compound will be 
embodied in the form of a liquid composition; for example, an emulsion, 
suspension, or aerosol spray. While the concentration of the active 
pesticide in the present compositions can vary within rather wide limits, 
ordinarily the pesticide compound will comprise between about 0.01 and 
about 80% by weight of the composition.