FR2581068A1 - Inclusion complex of a phosphorus-containing organic calcium compound and of cyclodextrin, process for its preparation and its use for protecting plants - Google Patents

Abstract

The present invention relates to an inclusion complex of general formula (I): 1. Inclusion complex of general formula (I): where CD is a group obtained by removing 1/n hydroxyl groups from a cyclodextrin molecule - preferably beta -cyclodextrin - and n is a value between 0.2 and 0.3, which is the inclusion complex of a complex of calcium bis[O-methyl O-(2,2-dichlorovinyl) phosphate] and of 2 moles of O,O-dimethyl O-(2,2-dichlorovinyl) phosphate formed with cyclodextrin, preferably with beta -cyclodextrin.

Description

 The present invention relates to a plant protection agent, a process for its preparation, the new active ingredient and a process for its preparation.

où
CD est un groupe obtenu en enlevant 1/n groupes hydroxy d'une
molécule de cyclodextrine - de préférence de 13-cyclodextrine
et n est une valeur comprise entre 0,2 et 0,3 qui est le complexe d'inclusion d'un complexe de calcium-bis-O-méthyl-(2,2- dichlorovinyl)-phosphate et de 2 moles de D,0-diméthyl-0-(2,2-dichlorovinyl)- phosphate formé avec la cyclodextrine, de préférence avec la B-cyclodextrine. According to one characteristic of the invention, there is provided an inclusion complex of general formula (I)

or
CD is a group obtained by removing 1 / n hydroxy groups from a
cyclodextrin molecule - preferably 13-cyclodextrin
and n is a value between 0.2 and 0.3 which is the inclusion complex of a calcium-bis-O-methyl- (2,2-dichlorovinyl) -phosphate complex and 2 moles of D, 0-dimethyl-0- (2,2-dichlorovinyl) - phosphate formed with cyclodextrin, preferably with B-cyclodextrin.

 It is known that 0,0-dimethyl-0-t2,2-dichlorovinyl) -phosphate (hereinafter called DDVP) is a very active pesticide. The preparation and use of phosphate complexes comprising metals are described in several patents.

British patent N 1 108 467 and Dutch patent
N 6 508 497 describe the insecticidal and acaricidal effect of metal complexes of organic phosphorus compounds. One of said metal complexes is the calcium-bis-0-methyl-0- (2,2-dichlorovinyl) -phosphate complex formed with 2 moles of 0.0-dimethyl-0- (2,2-dichlorovinyl) - phosphate (called below
Dankyl). This complex corresponds to formula (II).

The preparation of metal complexes of formula (11) has been described for the first time in / Nippon Kagaku Zasaki 91, 657-663. (1970
N 7) / / Munetaka and Enomoto / and in British patent N 1108 467.

Said compounds have a long-lasting insecticidal and acaricidal effect.

The DDVP prepared before the complex of formula (II) forms a stable crystal inclusion complex with 13-cyclodextrin. The DDVP content of said complex is 16.2% if the components are used at a molar ratio of 1: 1. No escape from this inclusion complex
DDVP in the solid state and the active ingredient is released only when the complex is contacted with water. The preparation, properties and use of said complex are described in several articles / Migamoto, S., Mifune,
A., Okada, Y., Yoneda, T., DOS No. 2,422,316 (1974); Szente, Szejtli, J .: Acta
Chim. A. Sci. Hung., 107, 195 (1981) /.

 The 0.0-dialkoyl-O- (2,2-dichlorovinyl) phosphate compositions having an insecticidal and acaricidal effect have only a very short duration of action due to their unstable nature.

 The DDVP inclusion complex formed with cyclodextrin has advantageous properties, namely that the unstability and decomposition are significantly reduced compared to the active ingredient used as such.

 The object of the invention is to increase the duration of action of Dankyl, which is superior to DDVP in that it forms an inclusion complex of the active ingredient Dankyl. To this end, the active ingredient Dankyl has been subjected to biological and structural studies.

 The foregoing considerations and studies have resulted in the new Dankyl and s-cyclodextrin inclusion complex of formula (I) of the invention.

The inclusion complex of DDVP and 13-cyclodextrin is formed by a typical apolar-apolar interaction. On the other hand, Dankyl unambiguously belongs to the metallic coordination complexes. The prior art is quite silent as to teaching concerning any inclusion complex of a metallic coordination complex. If we take into account the size of the Dankyl molecule, the
Formation of such an inclusion complex was completely unpredictable. The DDVP molecule can lodge in the 13-cyclodextrin cavity. On the other hand, the metallic coordination complex in the shape of a cross, made up of four molecules and having a calcium ion in its center cannot be lodged in the cyclodextrin molecule. To introduce the DDVP "branches" of the metallic complex molecule of coordination in the form of a cross in 13-cyclodextrin in the form of an inclusion complex, a provision of 13-cyclodextrin with specific spatial dimensions must take place in the crystal lattice, its formation being barely conceivable.

 It has surprisingly and unpredictably been found that Dankyl forms with cyclodextrin a stable inclusion complex which is particularly suitable for the preparation of plant protection formulations.

When the complex is brought into contact with water, the Dankyl is gradually released and this allows the preparation of insecticide, acaricide and anthelmintic compositions having a prolonyated effect.

In the following experiments, the insecticidal activity is compared
at the Canke d'j'-c: tion of Dankyl and those of the Dankyl inclusion or on complex formed with ss-cyclodextrin.

 As a control organism, the WHO normal line of housefly (Musca domestica) is used. As an experimental method, the tarsal contact test is applied. The essence of said test consists in placing the animals on a surface of infected glass which is covered by petri dishes (diameter 9 mm). The mortality rate is determined (%) at the end of the first, second and fourth days (Table 1). Table 2 shows the destructive efficiency (%) as a function of time. The complex is used in aqueous solution and the standard is applied in a acetone solution.

TABLE 1
% mortality in houseflies
Insecticide Duration after Dose @
treatment, days / ug / Petri dish
3 10 30
Dankyl LO 44
Dankyl-B-CD complex o 26 79
Dankyl 2 o 38 62
Dankyl-ss-CD o 53 76 complex
Dankyt 4 O o 3t
Dankyl-B-CD O 23 80 complex
ç Compared to the content of pure active ingredient in the complex.

TABLE 2
Destructive efficiency,%
Duration of Dankyl Complex Dankyl-ss-cyclodextrin exp. 1 2 4 1 2 4 min. (days) (days) / 30 0 0 0 0 0 0 60 0 0 0 0 0 0 90 0 0 0 0 0 0 120 0 0 0 10 0 0 150 0 0 0 35 30 32 180 6 0 0 55 41 34 320 20 15 0 63 65 52
The above data shows that the duration of Dankyl in complex is greater. At the highest dose (30 89) on the fourth day after treatment of the glass surfaces the activity of Dankyl decreases to half the original value, while on the other hand the efficacy of the complex d inclusion of Dankyl and 13-cyclodextrin remains unchanged.

According to another characteristic of the invention, there is provided a process for the preparation of an inclusion complex of general formula (i) where
CD is a group obtained by removing 1 / n hydroxq groups from a
cyclodextrin molecule - preferably ij-cyclodextrin
and n is a value between 0.2 and 0.3 which is the inclusion complex of a calcium-bis-O-methyl- (2,2-dichlorovinyl) -phosphate complex and 2 moles of 0, 0-dimethyl-0- (2,2-dichlorovinyl) - phosphate formed with cyclodextrin, preferably with 13-cyclodextrin, in which a) the compound of formula (II) or a saturated solution of this complex formed is reacted with an alkanol containing from 1 to 4 carbon atoms with an aqueous solution or suspension of cyclodextrin and the crystalline product thus obtained is isolated; or b) kneading a saturated solution of the compound of formula (yarn) formed with an alkanol comprising from 1 to 4 carbon atoms with cyclodextrin.

 It is preferred to use the components in a molar ratio of 0.2-0.3 mole of the compound of formula (II) per one mole of cyclodextrin.

 According to a still different character of the invention, there is provided an insecticide, acaricide and anthelmintic composition comprising in an amount of 1-99% by weight an inclusion complex of general formula (I) - where CD and n are such that described above - in addition to the usual carriers, adhesives and other auxiliary agents generally used in pesticide formulations and possibly one or more known active ingredient (s) pesticide.

 According to yet another characteristic of the invention, there is provided a process for the preparation of inseticide, acaricide and anthelmintic compositions in which 1 to 99% by weight of an inclusion complex of general formula (I) is mixed - where CD and n have the meaning given above - with usual carriers, adhesives and other auxiliary agents generally used in pesticide formulations and possibly one or more known active pesticide ingredient (s).

 According to yet another characteristic of the invention, there is provided: an anthelmintic composition comprising in an amount of 1-99% by weight an inclusion complex of general formula (I) - where CD and n are as described - above - in addition to thermoplastics and possibly other auxiliary agents.

 Thus, the anthelmintic compositions can be prepared by mixing in a complex of general formula (I) in an amount of 1-99% by weight with a thermoplastic material and possibly with other auxiliary agents, by formulating the mixture thus contained.

 The advantage of thermoplastics is above all that they are slightly soluble in an acid medium and that they swell only under acidic conditions. Thus the dissolution and disintegration of the CD complex takes place only in the intestinal tract in the basic state and the active ingredient exerts its action in this part of the body.

 It is preferred to use a plastic mixture comprising 30-60% by weight of a conjugated diene, 70-40% by weight of a diene-monovinyl copolymer.

0.5-5 parts by weight of a wetting agent and in addition of thermoplastics, eg. ex. an acrylate polymer, PVC, polyvinyl acetate, polystyrene. ethylene-vinyl acetate copolymer, etc.

 As conjugated diene, butadiene, isoprene or chloroprene can be used.

 As the monovinyl component used for the copolymerization with diene, the following compounds can be applied: ethylene, propylene.

 styrene, vinyl chloride, vinyl acetate, acrylic nitrile, methyl acrylate, vinyl butyl ether, vinylidene chloride, methacrylic nitrile, alpha-methyl-styrene and methyl methacrylate. Besides the active ingredient and the plastic, other additives can be mixed into the mixture before the final formulation, e.g. ex. a stabilizer, a plasticizer and inert powders such as silicon dioxide, kaolin and talc.

 The following examples give other details of the invention, the scope of protection not being limited to said examples.

EXAMPLE
Preparation of the Dankyl inclusion complex formed with B-cyclodextrin
57.5 g (0.05 mol) of B-cyclodextrin are dissolved at 68 ° C. in 500 ml of distilled water. 11 g (0.02 mol) of Dankyle are dissolved in 250 ml of 96% by volume ethanol and the solution thus obtained is added slowly to the 13-cyclodextrin solution, stirring constantly. After you finish charging the Dankyle. the reaction mixture is cooled to room temperature with constant stirring for 4 hours, after which the mixture is left to stand at + 40 ° C. while cooling with ice for 12 hours. The precipitation of the crystal complex begins at a temperature of 42-45 C.

 The crystalline product is separated by Filtrat. and dried over phosphorus penloxide to constant weight. 43 g of a white crystalline product are thus obtained.

 The Dankyl content of the product is determined by elemental analysis, the chlorine content of the product being determined by elemental analysis and the Dankyl content is calculated from the value thus obtained. The Dankyl content is also determined by this method in the following examples.

Chlorine content: observed: 3.78%;
calculated: 5.42%.

Dankyle content: 11.6%.

Yield: 66.1X (based on 13-cyclodextrin), 45.4% (based on
Dankyle)
Melting point: uncharacteristic, the product browns at 280-300 C and chars when the temperature is increased.

EXAMPLE 2
57.5 g (0.05 mol) of 13-cyclodextrin are kneaded at 220 ° C. with a solution of 11 g (0.02 mol) of Dankyl and 20 ml of 96% ethanol by volume for one hour. An almost powdery product is obtained. The crystalline product is dried under an infrared lamp to constant weight. 67.0 g of a white microcrystalline product are thus obtained.

Chlorine content: observed: 5.31%;
calculated: 5.23X;
Dankyl content: 15.5%.

Yield: 93.4% (relative to B-cyclodextrin),
94.4 / 0 (compared to Dankyl).

 The thermal stability of the product thus obtained is lower than that which is obtained according to Example 1 because of the Dankyl (a few%) adsorbed on the surface.

 The obvious advantage of the kneading process is the increased yield and the elimination of the mother-in-law treatment.

EXAMPLE 3
57.5% (0.05 mol) of 13-cyclodextrin is stirred in 100 ml of water at room temperature. A solution of 11 9 (0.012 Ylole) of Dankyl and 250 ml of 96% by volume ethanol is added dropwise to the above aqueous suspension of 13-csclodextrin while stirring constantly.

 After having finished loading the Dankyl, the suspension is stirred at room temperature until the Dankyle drops disappear 3 next to the complex crystals (verification under the microscope). The operation requires approximately 48 hours of agitation.

 The product is removed by filtration and dried at room temperature over phosphorus pentoxide to constant weight.

 62.0 g of the product are thus obtained.

Chlorine content: observed: 4.41%
calculated: 4.88%
Dankyle content: 14.8%.

Yield: 91.8% (based on 13-cyclodextrin);
83.5% (compared to Dankyl).

EXAMPLE 4
11.35 9 (10 millimoles) of 13-cyclodextrin are dissolved in 100 ml of water at 68 C, after which 2.2 9 (2 millimoles) of Dankyl having disappeared, the temperature of the reaction mixture is maintained at 68 C for another 30 minutes, and the solution thus obtained is cooled by stirring constantly at 220C for about 4 hours.

 The reaction mixture is left to stand at a temperature between 0 ° C. and + 5 ° C. for 18 hours and the crystalline inclusion complex is isolated by filtration. The product is dried at room temperature to constant weight. 9.8 g of a white crystalline inclusion complex are thus obtained.

Chlorine content: observed: 2.97%;
calculated: 2.99%.

Dankyl content: 40.1%.

Yield: 77.6% (based on 13-cyclodextrin);
45.6% (compared to Dankyl).

EXAMPLE 5
X-ray diffraction studies
Results of the ray powder diffraction diagram
X of the Dankyl crystal inclusion complex formed with 13-cyclodextrin and that of "empty" 13-cyclodextrin are summarized in Table 3. As the "host" molecule is not crystalline, the significant differences between the diffraction patterns of the Dankyl inclusion complex formed with 3-csclodextrin on the one hand and 13-cyclodextrin "empty" crystallized in the same way on the other hand constitute direct proof of the existence of the complex in the crystalline state .

TABLE 3
Characteristic diffraction peaks (20 C) ss-cyclodextrin Dankyl inclusion complex
and ss-cyclodextrin
4.7 +++ 6 +
9.0 +++ 11.8 ++
12.5 +++ 12.5 ++
13.6 +++ 17.5 +
14.6 ++ 18.0 +
15.3 ++ 21.0 +
L8.2 +++
L9.0 +++
21.2 +++
22.8
27.5
EXAMPLE 6
Thermoanalytical studies
Experiments have shown that the thermostability of Dankyl complexed in B-cyclodextrin is considerably higher than that of the pure active ingredient. The active ingredient Dankyl prepared according to Example 3, heating it under nitrogen has a maximum loss of organic substance at a temperature of 141 ° C. (measured according to the "Thermal Evolution Analusis": TEA). When heating the complex d 'inclusion of Dankyl and 8-cyclodextrlne, a net maximum occurs at 1950C due to the decomposition of the complex. Below this temperature, no organic substance is released from the inclusion complex of Dankyl and 13-csclodextrinew The DTA curves' Differential Thermogravimetral Analysis "- Dankyl, of a mixture of Dankyl and ss-cyclodextrin and the Dankyl inclusion complex formed with B-cyclodextrin also exhibit characteristic differences.

EXAMPLE 7
We mix with vonå an inclusion complex of Dankyl and
B-cyclodextrin comprising 25 parts by weight of active ingredient Dankyl, 60 parts by weight of a thermoplastic resin (copolymer of 54 parts by weight of butadiene, 20 parts by weight of methyl methacrylate, 25 parts by weight of styrene and 1 part by weight of divinyl-benzene) and partial by weight of methyl methacrylate, and the mass thus obtained is extruded into particles having a particle size of 1.5 × 3.0 mm.

EXAMPLE 8
A Dankyl and ss-cyclodextrin inclusion complex is thoroughly mixed comprising 25 parts by weight of Dankyl, 7G parts by weight of a thermoplastic resin (copolymer of 40 parts by weight of butadiene, 29.5 parts by weight of methyl methacrylate, 30 parts by weight of styrene and 0.5 parts by weight of divinyl-benzene) and 5 parts by weight of dioctyl phthalate, and the mixture thus obtained is extruded into particles having a particle size of 1.5 x 3.0 mm.

EXAMPLE 9
A Dankyl and 13-cyclodextrin inclusion complex is thoroughly mixed comprising 25 parts by weight of Dankyl, 45 parts by weight of a thermoplastic resin (copolymer of 40 parts by weight of butadiene, 29 parts by weight of methacrylate - methyl, 30 parts by weight of styrene and 1 part by weight of divinylbenzene), 20 parts by weight of an ethylene / vinyl acetate copolymer and 10 parts by weight of Carpiex (fine silicon dioxide powder), and the mixture thus obtained is extruded into particles having a particle size of 1.5 x 3.0 mm.

Claims (6)

1. Inclusion complex of general formula (I)

 or CD is a group obtained by removing 1 / n hydroxy groups from a  cyclodextrin molecule - preferably ss-cyclodextrin  and n is a value between 0.2 and 0.3 which is the inclusion complex of a calcium-bis-O-methyl- (2,2-dichlorovinyl) -phosphate complex and 2 moles of 0, 0-dimethyl-0- (2,2-dichlorovinyl) - phosphate formed with cyclodextrin, preferably with ss-cyclodextrin. 2. Process for the preparation of an inclusion complex of general formula (I)

 or CD is a group obtained by removing 1 / n hydroxy groups from a  cyclodextrin molecule - preferably 13-cyclodextrin  and n is a value between 0.2 and 0.3 which is the inclusion complex of a calcium-bis-O-methyl- (2,2 dichlorovinyl) -phosphate complex and 2 moles of 0.0 -dimethyl-0- (2,2-dichlorovinyl) - phosphate formed with cyclodextrin, preferably with B-cyclodextrin, in which a) the compound of formula (II) is reacted

 or a saturated solution of this body formed with an alkanol containing from 1 to 4 carbon atoms with an aqueous solution or suspension of cyclodextrin and the crystalline product thus obtained is isolated; or b) kneading a saturated solution of the compound of formula (II) formed with an alkanol containing from 1 to 4 carbon atoms with cyclodextrin. 3. Method according to claim 2 wherein the components are used in a molar ratio of 0.2-0.3 mol of the compound of formula (II) per 1 mol of cyclodextrin.  4. Insecticide, acaricide and / or anthelmintic composition comprising in  an amount of 1-99% by weight an inclusion complex of general formula  (I) (where CD and n are as set out in claim 1) in addition to supports  commonly used adhesives and other auxiliary agents  in pesticide formulations and possibly one or more ingredient (s)  known pesticide active ingredients, 5. Anthelmintic composition comprising in an amount of 1-99% by weight an inclusion complex of general formula (I) (where CD and n are as set out in claim 1) in addition to thermoplastics and possibly other auxiliary agents. 6. Process for the preparation of insecticide, acaricide and anthelmintic compositions in which 1-99% by weight of an inclusion complex of general formula (I) is mixed (where CD and n have the same meaning as in claim 1) with usual carriers, adhesives and other auxiliary agents generally used in pesticide formulations and possibly one or more known active pesticide ingredient (s).