Title of Invention

"PROCESS FOR THE PREPARATION OF MONO/DI/POLYOL ESTER PESTICIDES"

Abstract

The invention relates to the development of a process for the preparation of novel pesticidal mono-, di- and/or polyol esters characterized by the reaction of compound(s) containing the diol or polyol moiety with another compound containing acyl moiety RCO- and/or aroyl moiety ArCO- wherein the reaction is carried out in an inert aprotic solvent and a need based presence of a catalyst at temperature range of 15-100 °C and wherein the linkage in reference is formed as a result of condensation of these moieties. These compounds are either mono-, di-, tri- or poly alkanoate or mixture of two or more of such products. The compounds either as such or in different solid or liquid formulations exhibit considerable activity against different pests particularly the root knot nematode Meloidogynae incognita, reniform nematode Rotylenchulus reniformis, and phytophagous fungi Rhizoctonia solani and Sclerotia rolfsii infecting agricultural crops.

Full Text

The invention relates to a process for the preparation of novel mono/di/polyol ester pesticides. More particularly, it relates to substituted mono-, di-, and polyol esters as effective pesticides such as fungicides, nematicides, and the like. Background of invention Public has become concerned about the toxic pesticide residues that might be found in food, ground water, and the environment. There is therefore an urgent need to identify new pest control chemicals, compositions and methods that are safe to the environment and non-target organisms. Recent research in plant resistance to insect pests has demonstrated that secondary plant products such as glycolipids, glycerolipids as well as free fatty acids and esters present in plant exudates not only provide in-built plant resistance to invading pests, but also exhibit activity against certain phytophagous insects and pathogens. Being highly safe, some of the related esters such as sucrose esters of palmitic, stearic, and oleic acids find wide application in food industry as emulsifiers in cakes, biscuits, shampoos etc or as stabilizers, wetting agents, and solubilizers for poorly water-soluble drugs/chemicals. These reports have aroused interest in the synthesis and development of structurally similar mono-, di- and polyol esters as benign pest control agents. So far no literature reports are available employing mono/di or polyalkanoate moiety in such molecules for pest control purposes. Prior art The literature is replete with examples of naturally occurring lower and higher chain fatty acids (Lalonde,R.T., Morris, C.D., Wong, C.F.,Gardener, L.C., Eckert, D.J., King Drand Zimmermann, R.H. J. Chem Ecol. 1979, 5:371), glycerolipids such as 1,2-diacyl, 1,3-diacyl-and 1,2,3-triacylglycerol (Matsuzaki T., Shinozaki, Y., Hagimori, M., Tobita, T., Shigematsu,, H. and Koiwa, A. Biosci. Biotech. Biochem. 1992, 56: 1565-1569), and glycolipids such as sugar esters (Severson R.F., Arrendale, R.F., Chortyk, O.T., Green, C.R., Thome, F.A., Stewart, J.L., and Johnson, A.W. J. Agric. Food. Chem. 1985, 33:870-875) exhibiting pest control properties. US patent 6,608,039 describes chemically synthesized sugar esters that are effective for the control of soft-bodied arthropods. In another US Patent 6,103,768, Savage et al describes fatty acids and their derivatives to control plant infections and pests. The use of fatty acid esters and alcohols has been earlier described for the control of powdery mildew on apple buds (US patent 3,931,413). US patent 4,002,775 describes microbiocidal food additives comprising 1 or 2-monolaurin polyol esters. Wax esters have also been reported to deter feeding of Locusta migratoria on sorghum (Atkin, D.S.J., Hamilton, R.J., and Bernays, E.A. J. Nat. Prod., 1982, 45: 694) and turnip rootfly on Brassica species (Shepherd, T., Robetson, G.W., Griffiths, D.W., and Birch, A.N.E. Phytochemistry 1997: 46: 83). Monoesters of alkenyl/alkynyl substituted glycols and glycerols obtained from idioblast cells of avocado (Persea americand) are also known to exhibit significant antifungal and insect growth inhibitory and feeding deterrent properties. Further naturally occurring alicyclic diol and polyol esters such as ryanodines, agarofuran and quassinoids derivatives are well known for their pest control properties. The availability of such natural esters in meager quantities has, however, been a serious constraint in their large-scale use. A need has, therefore, been felt to synthesize environmentally benign mono-, di-, and polyol esters with pesticidal activity. The present invention reports a process for the preparation of novel alkyl/aryl mono-, di-, polyol esters having unsubstituted or substituted alkyl aryl, aralkyl. cycloalkyl groups of varying chain lengths. The derivatives so obtained have been found as potential pesticides, particularly fungicides and nematicides. Objective of the invention An objective of the invention is to prepare novel pesticidal mono-, di- and/or polyol ester pesticides. Another objective is to establish bioactivity of these derivatives against various pests such as fungi, nematodes and others. The invention This invention relates to the development of a process for the preparation of novel pesticidal mono-, di- and/or polyol esters represented by the general formula I Ar/R-CO-O-RrOH, and formula II, Ar/R-CO-O-Ri-OCO-R/Ar, characterized by the reaction of compound(s) containing the diol moiety such as HO-RrOH or polyol moiety such as monosaccharide, disaccharide, and the like in I and II, with another compound bearing acyl moiety such as RCOC1 and/or ArCOCl to form a link -CO-O-R,-OH in I and CO-O-R1O-CO- in II , wherein the reaction is carried out in an inert aprotic solvent in a need based presence of a catalyst at temperature range of 15-100 °C and wherein the linkage in reference is formed as a result of condensation of these moieties yielding mono, di, or poly alkanoate esters. Esters so formed are exclusively mono, di, tri or poly alkanoate or mixture of two or more of such products. In the above generic formulae I, and II 'R' represents unsubstituted or substituted alkyl, alkenyl, or alkylyl group of varying chain lengths (C-l to C-18), aralkyl, cycloalkyl, haloalkyl, alkoxyalkyl, aryloxyalkyl, 'Ar' is substituted or unsubstituted aryl, alkylaryl, alkoxyalkyl, alkoxyaryl, phenoxyphenyl or the like group. 'Ri' in diols used to prepare esters of formulae I, and II are substituted or unsubstituted short and long chain alcohols such as ethylene glycol, propylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, methylalkane diols, butanediol, pentanediol, hexanediol, cyclohexanediol, heptanediol, cyclohexyloxy cyclohexane diol, catechol, resorcinol, phloroglucinol, phenoxyphenols, monosaccharides such as pentoses and hexoses, and/or disaccharides such as sucrose, maltose and the like. Diol functions in alicyclic and/or aromatic rings are located at 1,2-; 1,3-, or 1,4-positions. Acid chlorides [RCOC1, ArCOCl or ClOC-Ar-COCl] employed in the reaction are those obtained by the action of acids such as acetic-, chloroacetic-, cyclopropane carboxylic-, propionic, butyric, isobutyric, pentanoic, isopentanoic, hexanoic, 2-ethylhexanoyl, heptanoyl, octanoyl, pelargonyl, decanoyl, fatty acids, 2(4-chlorophenyl-3-methylbutanoic-, phenoxyaetic-, chlorophenoxyacetic, and substituted or unsubstituted phenylacetic, benzoic or phenoxy benzoic, with thionyl chloride. The structure of the diol/polyol esters have been confirmed by 'H NMR and mass spectroscopy. Typical reactions for the preparation of the said compound(s) of types I and II are given below. Ar/RCOCl i). HO-RrOH * Ar/ROCO-R,-OH I Ar/RCOCl ii). Ar/ROCO-Rt-OH Ar/ROCO-R,-OCOR/Ar II The compounds of the formulae I, and II have been used to combat nematode, and fungal infestation in agricultural crops either as such or in compositions comprising a compounds of formulae I, or II as an active ingredient together with inert carrier/diluent and/or other additives such as surfactants, synergists etc. to obtain a solid or a liquid preparation. Suitable solid diluents such as pumice, gypsum, kaolin, bentonite, talc etc, liquid diluent such as ketonic and aromatic solvents, along with suitable swelling agent, dispersing agent or emulsifying agent and other formulants are used to prepare powders, emulsifiable concentrates, solutions or other formulations. The composition may include a mixture of compounds of formulae I, and II and/or other ingredients including another pesticidal material e. g. an insecticide, fungicide, nematicide or synergist. The compound(s) / composition(s) of the invention have been found particularly effective in combating pests such as reniform nematode Rotylenchulus reniformis and phytophagous fungi Rhizoctonia solani and Sclerotium rolfsii. The compounds were also active against the root knot nematode Meloidogynae incognita, Examples Examples I-XV describe the preparation of compounds of formula I, and II. Their antifungal and nematicidal activities are exemplified under the head 'bioassay'. Example I. Ethlene glycol di-/i-propionate (1): Alkane diol/polyol for example ethylene glycol (0.62g, 0.1 mole), contained in a double necked flask was reacted with freshly prepared acid chloride namely n-propanoyl chloride (3.0g, 0.25 mole). The flask was heated to gentle refluxing on a water bath for time ranging from 30 minutes to 3 hours. After completion of the reaction, water was added, the product extracted in solvent ether and purified by either column chromatography, preparative TLC or distillation under reduced pressure to yield the desired product (yield 1.5g, 80-85%). The product was either exclusively mono, di or polyol ester or mixture of two or more such products. Example II. Ethylene glycol di-iso-butanoate (2): The method of example I was repeated using ethylene glycol (0.62g, 0.01 mole) and freshly prepared acid chloride namely iso-butanoyl chloride (2.60g, 0.025 mole) to yield the title compound, (yield 1.62 g, 80%). Example III. Ethylene glycol di-n-hexanoate (3): The method of example I was repeated using ethylene glycol (0.62g, 0.01 mole) and freshly prepared acid chloride namely n-hexanoyl chloride (2.65g, 0.025 mole) to yield the title compound (yield 2.06 g, 80%). Example IV. Ethylene glycol di-(2-ethyl) hexanoate (4): The method of example I was repeated using ethylene glycol (0.62g, 0.01 mole) and freshly prepared acid chloride namely 2-ethyl hexanoyl chloride (4.86g, 0.03 mole) to yield the title compound (yield 2.50 g, Example V. Ethylene glycol di n-octanoate (5): The method of example I was repeated using ethylene glycol (0.62g, 0.01 mole) and freshly prepared acid chloride namely n-octanoyl chloride (4.86g, 0.025 mole) to yield the title compound (yield 2.45 g, 80%). Example VI. Ethylene glocol di-pelargonate (6): The method of example I was repeated using ethylene glycol (0.62g, 0.01 mole) and freshly prepared acid chloride namely pelargonyl chloride (4.4g, 0.025 mole) to yield the title compound (yield 2.52 g, 80%). Example VII. Propylene glycol di-w-butanoate (7): The method of example I was repeated using propylene glycol (0.76g, 0.01 mole) and freshly prepared acid chloride namely n-butanoyl chloride (2.65g, 0.025 mole) to yield the title compound (yield 1.70 g, 80%). Example VIII. Propylene glycol di-iso-butanoate (8): The method of example I was repeated using propylene glycol (0.76g, 0.01 mole) and freshly prepared acid chloride namely iso-butanoyl chloride (2.65g, 0.025 mole) to yield the title compound (yield 1.75g, 80%) Example IX. Propylene glycol di n-hexanoate (9): The method of example I was repeated using propylene glycol (0.76g, 0.01 mole) and freshly prepared acid chloride namely n-hexanoyl chloride (2.65g, 0.025 mole) to yield the title compound (yield 2.2 g, 80%). Example X. Propylene glycol di (2-ethyl) hexanoate (10): The method of example I was repeated using propylene glycol (0.76g, 0.01 mole) and freshly prepared acid chloride namely 2-ethylhexanoyl chloride (4.86g, 0.03 mole) to yield the title compound (yield 2.5 g, 80%). Example XI. Propylene glycol di-decanoate (11): The method of example I was repeated using propylene glycol (0.76g, 0.01 mole) and freshly prepared acid chloride namely n-decanoyl chloride (4.75g, 0.025 mole) to yield the title compound (yield 3.0g, 80%) Example XII. Diethyleneglycol di n-propionate (12): The method of example I was repeated using diethyleneglycol (1.06g, 0.01 mole) and freshly prepared acid chloride namely propionoyl chloride (2.3g, 0.025 mole) to yield the title compound (yield 1.75g, 80%) Example -XIII. Triethyleneglycol di n-pentanoate (13): The method of example I was repeated using triethyleneglycol (1.5g, g, 0.01 mole) and freshly prepared acid chloride namely 2-pentanoyl chloride (3.0 g , 0.025 mole) to yield the title compound (yield 2.5 g, 80%)' Example XIV. 2-Methyl propane-l,3-n-propionate (14): The method of example I was repeated using 2-methyl propane- 1,2-diol (0.9g, 0.01 mole) and freshly prepared acid chloride namely «-propionoyl chloride (2.3 g,, 0.025 mole) to yield the title compound (yield 1.6g, 80%). Example XV. 2-Methyl propane-l,3-di-n-octanoate (15): The method of example I was repeated using 2-methyl propane-1,2-diol (0.9g, 0.01 mole) and freshly prepared acid chloride namely n-octanoyl chloride (4.05g, 0.025 mole) to yield the title compound (yield 2.7 g, 80%) Example XVI. Pentane-l,5-di-iso-butanoate (16): The method of example I was repeated using pentane-l,5-diol (1.04g, O.Olmole) and wo-butanoyl chloride(2.65g, 0.025 mole) to yield the title compound.(yield 2.0 g, 80%). Example XVII. 4-(4-O-n-propionylcyclohexyloxy)-cyclohexylpropionate (17): Cyclo-hexane -1, 4-diol (2.32g, 0.02 mole) was placed in the double necked flask fitted with a reflux condenser and a dropping funnel. The flask was heated to melt the diol and to the molten diol re-distilled n-propanoyl chloride (2.3g, 0.25 mole) was added drop-wise from the dropping funnel. The reaction was worked up as in example I to yield the title compound (yield 2.2g, Example XVIII. Sucrose dibutanoate (18): Sucrose (5.48g, 0.016 mole) was dissolved in N,N-dimethylformamide (20 ml) and pyridine (4 ml) by gentle heating and stirring. Butanoyl chloride (3.8g, 0.036 mole) was slowly added and the mixture stirred for 1 h at 65 °C. After completion of the reaction, sodium carbonate was added to decompose pyridine hydrochloride. The reaction mixture was then filtered and the filtrate evaporated under vacuo to yield sucrose dibutanoate as pale yellow liquid (Yield 65%). Bioassay Anti-nemic and anti-fungal activities were assessed against the root knot nematode Meloidogynae incognita, the reniform nematode Rotylenchulus reniformis and the phytophagous fungi Rhizoctonia solani and Sclerotium rolfsii causing extensive damage to agricultural crops. The compounds exhibited outstanding activity against the test organisms. Nematicidal activity against the reniform nematode Rotylenchulus reniformis: Pesticidal alkane diol/polyol mono/di/polyalkanoates of the general formulae 1 to 3 were screened for their nematicidal activity against the reniform nematode Rotylenchulus reniformis. The nematodes originally isolated from a single egg mass from castor roots were cultured, multiplied and maintained on cowpea plants raised in 30 cm earthen pots containing sterilized soil-sand mixture. The egg masses were handpicked and kept on two layers of tissue paper supported by aluminum wire gauge (8-10 µ size) in 10 cm size Petri dishes were filled with fresh water. After 4 days, the population of R. reniformis emerged in the suspension was determined by counting J 4 in one ml aliquot three times and the average of three counts was taken as pot population in one ml suspension. The test solution of different diol/polyol esters (1500, 750, 500, 250, and 125 ppm) were prepared by serial dilution of the stock solution (3000ppm) in 0.5% emulsified water. Suspension of J 4 was diluted with water to 100 ml to get approximately 50 juveniles/ml. To one ml of this nematode suspension in Petri dish, equal volume of test solutions was added separately to get the desired test concentrations of 750, 500, 250, 125 and 62.5 ppm respectively. Juveniles kept in water with ethanol served as control. For each count, three replicates were taken and treated for 72 hr to observe juvenile immobility. Revival test was performed for each treatment by decanting off the test solution and adding distilled water to the Petri dishes. The number of revived juveniles were counted and deducted from the number of immobile juveniles obtained in the previous reading taken after 72 hr. Juveniles found immobile after the revival test were considered as dead. Antifungal activity against Rhizoctonia solani and Sclerotium rolfsii: The alkane diol/polyol esters were screened for their antifungal activity by the poisoned food technique using potato- dextrose-agar (PDA) medium. Cultures of the test fungi were maintained on PDA slants at 25°C and were sub-cultured in Petri dishes prior to testing. The ready-made medium (39g) was suspended in distilled water (1000 ml) and heated to boiling until it had dissolved completely. The medium and the Petri dishes were autoclaved and stock solutions were prepared by dissolving the test materials (130 mg) in acetone (2 ml). The dilution of 1, 0.5, 0.25 and 0.125 ml of this solution in 65 ml of PDA medium gave test solutions of approximately 250, 100, 25 and 5 mg litre-1, respectively. Acetone (1 ml) served as control. The medium was poured in to a set of two Petri dishes (two replications) under aseptic conditions in a laminar flow hood and a 5 mm thick disc of fungus (spores and mycelium) cut from earlier sub-cultured Petri dishes, was placed at the center of the semi-solid medium and the lids of the dishes were replaced. The treated and control dishes were kept in a BOD incubator at 26 (± 2) °C till the fungal growth in the control dishes was almost complete (3-4 days). The mycelial growth of fungus (mm) in both treated and control Petri dishes was measured diametrically in three different directions and EC50 values (effective concentration for 50 % inhibition; mg ml-1) were calculated for inhibition of fungal growth using Basic LD50 Program, version 1.1. Table 1. Antifungal and nematicidal activity (µg ml-1) of some potential pesticidal alkane diol / polyolesters esters. (Table Removed) 4. We claim 1. A process for the preparation of novel pesticidal mono-, di- and/or polyol esters represented by the general formula I Ar/ROCO-Rt-OH, and formula II, Ar/ROCO- Ri-OCOR/Ar, characterized by the reaction of compound(s) containing the diol moiety such as HO-R|-OH or polyol moiety such as monosaccharide, disaccharide, and the like with another compound containing acyl moiety RCO- and/or aroyl moiety ArCO- to form a link -OCO-R,-OH in I and -OCO-R,-OCO- in II , wherein the reaction is carried out in an inert aprotic solvent in a need based presence of a catalyst at temperature range of 15-100 °C and wherein the linkage in reference is formed as a result of condensation of these moieties yielding mono, di, or poly alkanoate esters or their mixtures. 2. A process as claimed in claim 1 wherein 'R' in formulae I, and II, is either unsubstituted or substituted alkyl, alkenyl, alkylyl, aralkyl, alkoxyalkyl, aryloxyalkyl, cycloalkyl, haloalkyl or the like group of varying chain length. 3. A process as claimed in claim I wherein 'Ar' in formulae I, and II is substituted or unsubstituted aryl, alkylaryl, alkoxyaryl, phenoxyphenyl or the like. 4. A process as claimed in claim 1 wherein 'R,' in diots or polyols used to prepare esters of formulae I, and II are substituted or unsubstituted alcohols or phenols such as ethylene glycol, propylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, methylalkane diol, butanediols, pentanediols, hexanediols, cyclohexanediols, heptanediols, cyclohexyloxy cyclohexane diol, catechol, resorcinol, phloroglucinol, phenoxyphenols, monosaccharides such as pentoses and hexoses, or disaccharides such as sucrose, maltose and the like. 5. A process as claimed in claims 1-4 wherein diol functions in alicyclic and/or aromatic rings are located at 1,2-; 1,3-, or 1,4- positions. 6. A process as claimed in claims 1-5 wherein the resultant product is mono, di, tri or polyol ester or mixture of one or more of such esters. 7. A process as claimed in claim 1, wherein the inert organic solvent(s) uswed for carrying out the reaction include any one of benzene, toluene, xylene, methylenechloride, chloroform, ethylacetate, acetone, ethylmethylketone or methyl isobutylketone. 8. A process as claimed in claim 1 wherein catalyst includes a base such as triethylamine, pyridine, or the like.9. A process as claimed in any of the above claims and as exemplified in the body of the application, and the formulations containing these esters as such or in combination with various other formulants for use as pesticides in the control of agricultural pests such as root knot nematode Meloidogynae incognita, reniform nematode Rotylenchulus reniformis and phytophagous fungi Rhizoctonia solani and Sclerotium rolfsii infecting agricultural crops.

Documents:

847-delnp-2003-abstract.pdf

847-delnp-2003-claims.pdf

847-delnp-2003-correspondence-others.pdf

847-delnp-2003-correspondence-po.pdf

847-delnp-2003-description (complete).pdf

847-delnp-2003-form-1.pdf

847-delnp-2003-form-19.pdf

847-delnp-2003-form-2.pdf

847-delnp-2003-form-3.pdf

847-delnp-2003-form-5.pdf