MXPA96005600A - Naftoquin derivatives - Google Patents

Abstract

The present invention relates to certain furophthoquinone derivatives, some of which are novel, of formula (I), in which R represents a hydrogen atom or a hydroxyl group or an ethanoyloxy, the methods for their preparation, the compositions comprising such compounds and their use as pesticides, such as fungicides, and especially, insecticides and acaricides. The compounds of formula I can be derived from plants of the Calceolaria genus and the invention is therefore also related to the extracts of a Calceolaria species and its use as a pesticide.

Description

DERIVATIVES OF NAFTOQUINONA This invention relates to certain naphthoquinone derivatives, one of which is novel, methods for their preparation, compositions containing such compounds and their use as pesticides, such as fungicides, and, especially, insecticides and acaricides. "^ It has been found that the plant extracts of Calceolaria genus, particularly Calceolaria sessilis, Calceolaria andina and Calceolaria glabrata var. Meyenesis found in Chile, exhibit pesticidal activity. The purification and analysis of these extracts has resulted in the isolation and identification of certain naphthoquinone derivatives, which also exhibit pesticidal activity. According to the present invention there is thus provided a compound of general formula I wherein R represents a hydrogen atom or a hydroxyl or an ethanoyloxy group, to be used as REF: 23524 pesticide, for example, a fungicide and / or, especially, an insecticide and / or an acaricide. The compound of formula I may be in pure form or in admixture with one or more other compounds of formula I. It is particularly preferred that the compound of formula I, or at least one of the compounds of formula I, be one in which R represents an ethanoyloxy group. A compound of formula I, in which R represents a hydroxyl group can be tautomerized to form the corresponding 4-hydroxynaphthalene-1,2-dione and the invention therefore also includes this tautomer.

In addition, the compound of formula I in which R represents a hydroxyl group can form alkali metal salts or metals, such as sodium and potassium, and alkaline earth metals and those salts also form part of the invention. - As mentioned above, the extracts of plants of the Calceolaria genus are themselves active as pesticides. Thus, according to another aspect of the present invention there is provided an extract of a Calceolaria species to be used as a pesticide, for example, a fungicide and / or especially an insecticide and / or an acaricide. A partially purified extract of a Calceolaria species can be used. Preferably, the extract comprises at least one compound of formula I as defined above. The compounds of formula I or the extracts defined above can be obtained by extracting the material from the crushed plant, for example, the leaves and / or stems, from a Calceolaria species with a solvent. The initial extraction is preferably carried out with a hydrocarbon solvent such as an alkene, especially hexane, the extract is then concentrated, for example, by evaporation. The concentrated extract can then be purified by chromatography, suitably by column chromatography using a silica gel column, followed by an additional separation process. Preferably, the Calceolaria species is Calceolaria andina, Calceolaria sessilis and Calceolaria glabrata var. meyenesis The compounds of formula I can be used as a pesticide in the form of an extract as defined above. Alternatively, isolated compounds of formula I or extracts of a Calceolaria species can be formulated with an inert carrier or diluent to produce a pesticidal composition. According to a further aspect of the present invention there is thus provided a pesticide, for example, fungicide and / or, especially, an insecticide and / or acaricide, which composition comprises a carrier and, as an active ingredient, a compound of formula I as defined above or an extract of a Calceolaria species as defined above. The compositions of the invention may contain from 0.001 to 95% by weight of the active ingredient of the formula I. Preferably, the compositions contain from 0.001 to 25% by weight of the active ingredient when in ready-to-use form. Nevertheless, higher concentrations, for example, of up to 95% may be present in the compositions to be sold as concentrates to be diluted before use. The compositions of the invention can be mixed with a variety of suitable inert carriers such as solvents, diluents and / or surfactants to form powders, granulated solids, serpentine wettable powders for mosquitoes or other solid preparations or emulsions, emulsifiable concentrates, sprays, aerosols or other liquid preparations. Suitable solvents and diluents include water, aliphatic and aromatic hydrocarbons such as xylene or other petroleum fractions and alcohols such as ethanol. The surfactants may be of an anionic, cationic or non-ionic type. Antioxidants or other stabilizers may also be included as well as perfumes and colorants. The inert carriers can be of the type and in proportions such as those conventionally used in pesticide compositions. In addition to these inert carriers, the compositions of the invention may also contain one or more additional active ingredients. Those additional active ingredients may be other compounds that exhibit pesticidal activity and those other compounds may exhibit a synergistic effect with the compounds of the present invention. The compounds of formula I and the extracts of a Calceolaria species as defined above can be used to control infestation with pests or parasites in domestic, horticultural, agricultural, medical or veterinary environments. Thus, according to another aspect of the present invention there is provided the use as a pesticide, for example, of a fungicide and / or especially, an insecticide and / or acaricide, of a compound of formula I as defined above, a extract of a Calceolaria species as defined above or a composition as defined above. The present invention also provides a method for combating pests, such as fungi and / or especially, insects and / or mites, in a location, which comprises treating the site with a compound of formula I as defined above, an extract of a Calceolaria species as defined above or a composition as defined above. Preferably, the site comprises the pest per se or environments subject to or subjected to attacks by pests. More preferably, the site comprises the pests per se, food material fed, plants or animals subject to or subject to attacks by pests, seeds of such plants or the environment in which such plants grow or will grow. Especially, the compounds of formula I, extracts and compositions as defined above can be used in a domestic environment to spray rooms to combat infestation by houseflies or other insects, in a horticultural or agricultural environment for the treatment of stored crops, especially cereals. , or to spray growing crops such as cotton or rice to combat infestation by fungi, insects or other pests, and in medical or veterinary environments, for example, as a spray for livestock to prevent or treat infestation by insects or other pests The synthesis of the compound of formula I, in which R represents a hydroxyl group is described by R. G Coo e in Aust. J. Sci. Res., (1950), pp. 481-486 and the 13 C NMR spectrum of this compound is described by I.A.

McDonald, T.J. Simpson and A.F. Sierako ski in Aust. J.

Chem., (1977), 30, pp 1727-34. In addition, the isolation of the compounds of formula I, in which R represents a hydroxyl group or ethanoyloxy of the aerial parts of Calceolaria sessilis and the physical characterization of these compounds is described by M.N. Chamy, I. Jiménez, M. Piovano, J.A. Garbarino and B.

Didyk in Biol. Sec. Chil. Quim (1993), 38 'PP 187-190. However, the remaining compounds of formula I could seem novel. According to a further aspect of the present invention, there is thus provided a compound of general formula I as defined above, which R represents a hydrogen atom or an ethanoyloxy group. The compound of formula I, in which R represents an ethanoyloxy group can be prepared by reacting the compound of formula I, in which R represents a hydroxyl group with an ethanoyl halide, especially ethanoyl chloride. Preferably, the The reaction is carried out in the presence of a solvent. Suitable solvents include chlorinated hydrocarbons, such as dichloromethane, aromatic and heteroaromatic compounds, such as pyridine, and mixtures thereof. It is also preferred that the reaction be carried out at a temperature in the range of 0 ° C to 40 ° C, more preferably 15 ° to 30 ° C, with ambient temperatures (of about 20 ° C) being especially preferred. The compound of formula I, in which R represents a hydroxyl group can be prepared by refluxing 2- (3-methylbut-2-enyloxy) naphthalene-1,4-dione in an alcohol, preferably absolute ethanol. 2- (3-Methylbut-2-enyloxy) naphthalene-1,4-dione can be prepared by reacting 2-hydroxynaphthalene-1,4-dione with triphenylphosphine and diethyl azodicarboxylate followed by 3-methylbut-2-enol in the presence of a solvent, such as tetrahydrofuran. 2-hydroxynaphthalene-l, 4-dione (otherwise known as Lawsone or Henna) is a known compound that is commercially available. The invention is best illustrated with the following examples: Example 1 Extraction procedure The material from the crushed plant (450 g) of Calceolaria andina from Chile was extracted with hexane (2 x 1500 ml) using microwave radiation (Panasonic NN-6452B, 800, 3 minutes). The combined extracts were evaporated to dryness under reduced pressure to yield a green oil (10.8 g) (Extract A). The residue was eluted under silica gel suction (Silicone Gel 60H, Merck 7736) with a mixture of petroleum and ether (2: 1), to give two active fractions which were then combined (4.79 g). The combined active fractions were eluted from the silica gel (Silica Gel 60, Merck 9385) with a mixture of petroleum and ether (4: 1). The main components were combined and evaporated to dryness (3.81 g). The major components (1.76 g) were dissolved in ether (50 ml) and extracted with saturated, aqueous sodium carbonate solution (4 x 50 ml). The combined basic fractions were acidified to pH 5 with 2M hydrochloric acid and extracted with ether (3 x 40 ml). The combined ether extracts were washed with water (2 x 25 ml), saturated with aqueous sodium chloride solution (25 ml) and dried over magnesium sulfate. Filtration and evaporation of the solvent under reduced pressure yielded a red solid (226 mg), m.p. 60 ° C, identified by NMR as the compound of formula I, in which R represents a hydroxyl group (Compound B).

The remaining organic layer was washed with saturated aqueous sodium chloride solution (25 ml) and dried over magnesium sulfate. Filtration and evaporation produced a reddish solid (1.53 g). The reddish solid (1.50 g) was eluted from the silica gel (Silica Gel 60, Merck 7736) using a mixture of petroleum and ether (4: 1) and two compounds were isolated. The less polar compound (48 mg) was identified as the compound of formula I, wherein R represents a hydrogen atom (Compound A) while the second, the more polar compound (1.14 g), m.p. 55 ° C, was identified as the compound of formula I, in which R represents an ethanoyloxy group (Compound C). The tH NMR and 13C NMR spectra (obtained for a solution in CDC13, using tetramethylsilane as the internal standard, on a JEOL GX-400 400 MHz spectrometer for XH NMR and 100 MHz for the 13C NMR) showed the peaks shown in the Table I next.

*-** TABLE 1 No. assigned to the Compound atom? (PH) d ppm carbon (see formula) H 'C 1 - 184.5 2 6.89 (s ^ 134.4 3 - 156.7 4 - 185.8 5 8.02-8.05 (m) 125.6 6 7.68-7.7 (m) 133.8 7 7.68-7.7 ( m) 133.4 8 8.05-8.07 ím) 126.9 9 - 131.5 10 - 133.3 11 - '41.0 12 6.18 (dd, 17.3.10.4> 145.4 13 5.08 (d, lC) 112.7 5.05 (d, 17.3) > 14 1.46 ( s) 27.1 15 1.46 (s) 27.1 16 17 s = simplete, d = doublet, dd = double doublet, dt = double 10 triplet, m = multiplet The characters in parentheses are constants of accommodation (J) in Hz.

TABLE 1 (continued) No. assigned to the atom of Compound B (R = OH) d ppm carbon (see formula) XH 1JC 1 - 182.2 2 OH 7.89 (s) 152.9 3 - 128.4 4 - 184.8 5 8.05 (d, 7.6) 127.0 6 7.74 ( dt, 1.2.7, 6) 135.2 7 7.65 (dt, 1.2.7.6) 132.6 8 8.03 (d, 7.6) 125.8 9 - 128.2 10 - 134.1 11 - 41.0 12 6.29 (dd, 17.4.10.4) 148.1 13 4.96 (d, 10.4) 109.6 4.98 (d, 17.4) 14 1.57 (s) 28.1 15 1.57 (s) 28.1 16 17 s = if full, d = doublet, dd = double doublet, dt = double triplet, m = multiplet The characters in parentheses are coupling constants (J) in Hz.

/ - " TABLE 1 (continued) No. assigned to the atom of Compound C d ppm carbon (see formula) (R = OClbOC1 H3) 1JC XH 1 - 178.6 2 - 150.7 3 - 143.9 4 - 185.1 5 8.03 (d, 7.0) 126.8b 6 7.73 (dt, 1.2.7. 0) 134.3C 7 7.69 (dt, 1.2.7. 0) 133.4C 8 8.03 (d, 7.0) 126. lb 9 - 133.4a 10 - 133.0a 11 - 41.5 12 .19 (dd, 17.4, 10 .4) 147.2 13 4.99 (d, 10.4) 109.5 4.96 (d, 17.4) 14 1.53 (s) 27.6 15 1.53 (s) 27.6 16 168.3 17 • 2.32 (s) 20.7 The assignments marked a, b, c are interchangeable, s = simplete, d = doublet, dd = double doublet, dt = double triplet, m = multiplet The characters in parentheses are coupling constants (J) in Hz. 10 Example 2 Alternative Extraction Procedure The material from the crushed plant (100 g) of Calceolaria andina was placed in hexane (500 ml) for 2 hours before stirring for 10 minutes. The solvent was filtered and the residue was further extracted with hexane (2 x 500 ml). The combined hexane extracts were evaporated to dryness to give a green solid (2.23 g) (Extract B). This was separated as described in Example 1.

Example 3 Preparation of 2- (1, 1-dimethyl-lprx ^ -2-enyl) -3-hydroxynaphthalene-1, -dione (Compound B. Formula I: R = -OH) (i) Preparation of 2- (3-methylbut-2-enyloxy) naphthalene-1,4-dione To a stirred solution of 2-hydroxynaphthalene-1,4-dione (10.0 g, 57.4 mmol) and triphenylphosphine (15.1 g, 57.4 mmoles) and dry tetrahydrofuran (150 ml) at 0 ° C under a nitrogen atmosphere was added diethyl azodicarboxylate (10.0 g, 57.4 mmoles). After stirring for a further 5 minutes, a solution of 3-methylbut-2-enol (7.42 g, 86.1 mmol) in dry tetrahydrofuran (10 ml) was added dropwise and stirring was continued for 2 hours. The precipitate was collected, dried in air and recrystallized from aqueous methanol to give the title compound (8.3 g) as a yellow crystalline solid with a melting point of 138 ° C.

X H NMR (400 MHz) d 1.76 (s, 3 H, 3 x H-15), 1.81 (s, 3 H, 3 x H-14), 4.59 (d, 2H, J «6.9 Hz, 2 x H-ll), 5.49 (t, 1H, J = 6.9 Hz, H-12), 6.16 (s, H-3), 7.68- 7.76 (m, 2H, H-6 and H-7), 8.06-8.13 (m, 2H, H-5 and H-8). 13 C NMR (100 MHz) d 18.4 (15), 25.8 (14), 66.4 (11), 110.5 (3), 117.2 (12), 126.1a (5), 126.7a (8), 131. lb (9) , 132.0b (10), 133.2 ° (7), 134.2C (6), 140.5 (13), 159.5 (2), 180.3 (1) and 185.0 (4) where a, b or c are interchangeable assignments. (ii) Preparation of 2- (1, 1-dimethylprop-2-enyl) -3-hydroxynaphthalene-1,4-dione A solution of 2- (3-methylbut-2-enyloxy) naphthalene-1,4-dione (4.27 g, 24.8 mmol) obtained in (i) and above in absolute ethanol (125 ml) was refluxed for 6 hours. The mixture was cooled and the solvent was removed in vacuo. The residue was dissolved in diethyl ether and extracted with 1% (weight / volume) aqueous sodium hydroxide solution (6 x 25 ml). The combined basic fractions were acidified to pH 5 with 2M hydrochloric acid and extracted with diethyl ether (6 x 25 ml). The combined ether extracts were washed successively with water (2 x 25 ml) of saturated aqueous sodium chloride solution (25 ml) and dried over anhydrous magnesium sulfate. Filtration and evaporation of the solvent under reduced pressure followed by recrystallization of aqueous methanol, produced the title compound (4.27 g) as a yellow crystalline solid, p. F. 60 ° C.

Example 4 Preparation of 2- (1, 1, Jmatilprsp-2-enyl) -3-ethanoyl-cDNA-naphthalene-1,4-dione (Compound C, Formula I: R - -O-CO-CH3) To a stirred solution of 2- (1,1-dimethylprop-2-enyl) -3-hydroxy-naphthalene-1,4-dione (20.0 g, 82.6 mmol) obtained as in Example 3 above in a dichloromethane mixture After drying (250 ml) and pyridine (50 ml) at 0 ° C., a solution of ethanoyl chloride (25.9 g, 330 mmol) of dichloromethane (25 ml) was added slowly over 40 minutes. slowly to room temperature for 2 hours before washing successively with water (50 ml), 2M hydrochloric acid (2 x 50 ml), water (2 x 50 ml), saturated aqueous sodium carbonate solution (2 x 50 ml) water (2 x 50 ml), saturated sodium chloride solution (50 ml) and dried over magnesium sulfate, filtration and evaporation of the solvent under reduced pressure and recrystallization from aqueous methanol gave the title product (21.6 g). g) as a yellow crystalline solid m.p. 55 ° C.

Example 5 Pesticidal Activity Pesticide activity was evaluated against house flies, mustard beetles, diamondback butterflies, termites and whiteflies using the following methods.

Domestic flies (MD) (Musca domestica) The female flies were treated on the thorax with a drop of one microliter of test compound dissolved in acetone. Two replicates of 15 flies were used at each dose unit and 6 unit doses per compound under test were used. After the treatment, the flies were kept at a temperature of 20 ° ± 1 ° C and the mortality was evaluated 24 and 48 hours after the treatment. The values of the DLYO in the microorganisms of the fly test compound were calculated (see Sawicki et al., Bulletin of the World Health Organization, 35, 893 (1966) and Sawicki et al., Entomology and Exp. Appli 10 , 253, (1967).

Mustard beetles (PC) (Phaedon cochleariae fab) A one microliter drop of an acetone solution of the test compound was applied ventrally to adult mustard beetles using a microdroplet applicator. The treated insects were maintained for 48 hours, after which the mortality was evaluated. Two replicates of 20 to 25 mustard beetles were used each at each dose level and 5 dose levels were treated in a comparable manner. The values of the DL were calculated, or as for the house flies.

Diamondback butterfly (PX) (Plutella xylostella) Fifty in the initial stage were treated with a drop of 0.5 μl of test compound in acetone. Three replicates of 10 larvae each were used at each unit dose and 5 unit doses were used per compound under test.After treatment, the larvae were maintained at approximately 22 ° C, and mortality was evaluated as failure. 5 days later, the values of the LD50 were calculated as for house flies.

Termites (TU) (Tetranychus urticae) 25 adult female termites were immersed in 35 μl of a solution of the test compound in a 1: 4 acetone-water mixture for 30 seconds. The treated insects were maintained at 21 ° ± 2 ° C and the mortality was evaluated 72 hours after the treatment. The termites who exhibited repetitive (non-reflex) movement of more than one of the locomotor appendages after this period were recorded as alive. Three replicates of 25 termites were used each at each unit dose and 5 or 6 unit doses were used per compound under test. They were calculated the values of the CL5o in ppm of solution of the test compound per insect. The test was carried out using three different strains of termites, one susceptible (GSS) and the others (NYR-Bif-1000 and UK-S-Carb-600) resistant to bifenthrin and carbaryl respectively. The GSS strain was provided by Schering, AG, Berlin. The NYR-Bif-1000 strain was provided by the Entomology Department, Cornell University, New York, having submitted a field test to the selection with a bifenthrin. Strain UK-S-Carb-600 was obtained by applying the selection with carbaryl to the strain UK-S provided by Shell Research Limited, Sttingbourne. (See T.J. Dennehy, A.W. Farnham and I. Denholm, Pestic. Se, 39.47-54, (1993).

White fly (BT) (Be ißia tabaci) Acetone solutions (0.100 ml) of the test compounds were placed in 10 ml glass bottles and rotated to deposit a film of the context. Thirty adult white flies were placed inside the bottle, 60 minutes later, the treated insects were transferred to untreated cotton leaf discs, which were kept wet on a bed of agar gel. The temperature was maintained at 25 ° C and the mortality was evaluated 48 hours later. Three replicates of each of the 5 to 7 dose levels per compound were used. The CL5o values were calculated using a computer software package ("Polo-PC" available from LeOra Software, Berkeley, California). (See M.R. Cahill and B. Hackett in Proceedings Brighton Crop Protection Conference, 1992). The test was carried out using three different strains of whitefly, one susceptible and two resistant to pyrethroid insecticides. The susceptible strain (SUD-S) was collected in Sudan in 1978 from cotton, a resistant strain (Ned 3) was collected in Holland in 1992 from gerbera and the other resistant strain (USA-B) was collected in the southern United States in 1985 of poinsettia). The results of these tests are shown in Tables 2 and 3 below. The values are given as DL ^ o (μg / insect) or LC50 (ppm of test compound solution) unless otherwise specified.

TABLE 2 f *% mortality at 20 μg / insect **% mortality at 10 μg / insect *** mortality assessed at 24 hours instead of 48 hours.

TABLE 3 % mortality at 20 μg / insect mortality at 10 μg / insect 10 Example 6 Activity against the white fly (TV) (Trialeurodes vaporariorum) 15 A leaf disk was immersed in a solution of 40% acetone: water of Compound C and then allowed to dry. The adult white flies were then confined in a Petri dish with the treated leaf. Four replicates of 10 adult white flies were used for each unit dose. Mortality was evaluated at specific times after treatment and the mortality percentages were calculated, corrected using the Abbott formula. The results of this test are given in Table 4. TABLE 4 These results indicate an LC50 of 10-100 ppm for Compound C against this insect. The tests also show that the compounds of formula 1 exhibit amateur activity against several aphid species, especially Myzus persicae and Aphis gossypii.

In addition, tests have shown that the compounds of formula I exhibit good fungicidal activity against a broad spectrum of fungi, which cause diseases in leafy leafy leaf crops. Particularly good activity has been observed against fungi of the genus Erysiphe, especially Erysiphe graminis, Botrytis, especially Botrytis fabae and Botrytis cinerea, Rhizoctonia, especially Rhizoctonia solani and Rhizoctonia cerealis, Pyricularia, especially Pyricularia oryzae, and Aspergillus, especially Aspergillus niger. It is noted that in relation to this date, the best method known by the applicant to carry out the aforementioned invention is that which is clear from the present description of the invention. Having described the invention as above, property is claimed as contained in the following:

Claims (12)

1. A compound of the general formula I characterized in that R represents a hydrogen atom or a hydroxyl group or an ethanoyloxy, to be used as a pesticide.
2. 2. The compound according to claim 1, characterized in that R represents an ethanoyloxy group.
3. 3. An extract, characterized because it is from a Calceolaria species to be used as a pesticide.
4. 4. An extract according to claim 3, characterized in that it comprises at least one compound of formula I according to claim 1 or claim 2.
5. 5. The extract according to claim 3 or claim 4, characterized in that it has been obtained by extracting crushed plant material from a Calceolaria species with a solvent.
6. 6. The extract according to any of claims 3 to 5, characterized in that the Calceolaria species is Calceolaria andina, Calceolaria sessilis or Calceolaria glabrata var. meyenenis
7. 7. The extract according to any of claims 3 to 6, characterized in that it is substantially as described herein and with reference to Example 1 or Example 2.
8. 8. A pesticidal composition, characterized in that it comprises a carrier, as an active ingredient, a compound of formula I according to claim 1 or claim 2 or an extract according to any of claims 3 to 7.
9. 9. The composition according to claim 8, characterized in that it is substantially as described herein.
10. 10. A method for combating pests or parasites in a location, characterized by comprising treating the site with a compound of formula I according to claim 1 or claim 2, an extract according to any of claims 3 to 7 or a composition of according to claim 8 or claim 9.
11. 11. The use as a pesticide of a compound of formula I according to claim 1 or claim 2, an extract according to any of claims 3 to 7 or a composition according to claim 8 or claim 9.
12. 12. A compound of general formula I according to claim 1, characterized in that R represents a hydrogen atom or an ethanoyloxy group.