2-ALKENE-PHOSPHONATES AND PROCESS FOR THEIR PRODUCTION

Abstract: 2-Alkene-phosphonates of the formula are valuable intermediates for the production of pyrethroids. Described is also a process for the production of the new compounds.

Description: The present invention concerns intermediates for the product ion of new insecticide and acaricides belonging to the class of pyrethroids. These new compounds have the general formula I: EMI1.1 wherein: R1 = F, C1, Br, CH3, CF3; 2 R = F; Cl, Br, CF3; R6 = H1 F, Cl, Br; R7 and R81 equal to or different from each other, = alkyl or haloalkyl with C1-C4, or R7 and R8 together constitute a EMI1.2 group or a EMI1.3 group, provided that when R1 t CH3, R will be different from C1. The new compounds may be prepared by the following reactions 1 to 8 EMI1.4 EMI2.1 In the above reported reaction R1, Rr R6, R7 and RB, if notj otherwise indicated, have the meanings reported for formula I; X stands for chlorine or bromine while NBS indicates N-bromo-succinimide.¯Reactions from 1 to 4 represent examples of methods for the preparation of the corn pounds of formula I: wherein R6=H. The compounds wherein R6 = halogen, may be prepared in a similar way starting from suitable 2-alkenyl halides, or they may be prepared from the compounds of formula I wherein R = H, by the methods illustrated by reactions from 5 to 8. All starting compounds of reaction 1 to 4 are known compounds or they can be easily prepared according to known methods. Reaction 5 concerns a standard halogenation in allylic position, carried out with N-bromo-succinimide. Reactions 6 to 8 represent an alternative to reaction 5, also useful for preparing compounds in which R6 = Cl. The addition of halogen (X2) to compounds I wherein R6=N (reaction 6) is carried out according to techniques that are standard in organic chemistry, using halogens or halogenating agents such as SO2Cl2. The dehydrohalogenation of adduct(III) (reaction7) may be carried out either in the presence of inorganic bases or of organic bases such as secondary or tertiary amines. The reaction of the re-arrangement of adducts (IV) (reaction 8) is a new one and as such forms a further object of this invention. Said reaction accours quantitatively at a temperature comprised between 200 and 1500C, in the presence of catalytic quantities of a bivalent copper halide, by simple stirring of the mixture consisting of the adduct (IV) and of cupric halide. In case X = Cl, a suitable catalyst is cupric chloride in the commonly used form of dihydrate. The new intermediates are.useful in the preparation of valuable insecticides and acaricides of the pyrethroid series. The new insecticides have the general formula (A) EMI4.1 wherein R1 = F, C1, Br, CH3, CF3, R2 = F, C1, Br, CF3, R6 = H, F, Cl, Br, EMI4.2 in which R5 = H, CN, -C=CH. The new insecticides (A) were prepared starting from the new intermediates by reacting in the presence of a strong base a 2-alkene-phosphonate of the above mentioned formula (I EMI4.3 wherein the residues R1, R3, R6, R7 and R8 are defined as above, with a lower alkylester of caronic aldehyde (V) (2,2-dimethyl-3-formyl-cyclopropanecarboxylic acid) of the formula: EMI4.4 (wherein: R/ O-alkyl C1-c,) The above process, is illustrated by reaction 9 ): EMI5.1 The compounds of formula I have been indicated as phosphonates, thereby using this term in its more general meaning, that is, referred to organic compounds of the pentavalent phosphorus in which there is present a carbon-phosphorus bond. It must, however, be pointed out that the correct nomenclature for the compounds of formula I (in which substi tuents R7 and R8 tuents R and R together represent either a EMI5.2 or a EMI5.3 group and thus form with the EMI5.4 group either a pentastomic or hexaatomic ring) foresees for these compounds the term 2-oxo-1,3,2-dioxaphospholane and respectively 2-oxo-1,3,2-dioxa-phosphorinane. In this context, the compounds of formula I will in the following be indicated by the term "phosphonates", also comprising thereby the compounds of formula I in which there occurs either a penta- or hexatomic ring. As far as we know, only one example of a reaction between a 2-alken-phosphonate and an aldehyde was known from the literature. Said example concerns the reaction between methyl 3-chloro -2-butene-phosphonate and benzaldehyde tG. Lavielle, C.R. Acad. Sci., Ser. C, 86 (1970)5. The above cited reaction leads to the formation of three products, only one of them having a dienic structure: EMI6.1 It had thus to be expected that also from reaction9 there would form compounds of little interest for the purpo ses of the desired structure. On the contrary, we surprisingly found that reaction 9 affords compounds of formula A' with high yields and allows to separate isolate) the desired product quite easily and with a high degree of purity. Reaction 9 is carried out using substantially equimolar quantities of phcsphonate I- and of the ester of caronic aldehyde (V), in the presence of substantially eaiiro1 lar amounts of a strong base, in an inert solvent or diluent and at temperatures comprised between -50 C and +1000C, but preferably comprised betwecn -30 C and room temperature, Suitable strong bases may be hydrides or hydroxides of alkaline metals such as sodium hydride, lithium hydride, sodium hydroxide, potassium hydroxide, etc. In case that as a base there is used sodium hydride, it is preferable to operate in the presence of catalytic amounts of suitable activators such as for instance ethyl alcohol or imidazole. As a reaction medium there may be used an ether such as for instance: dimethoxy-ethane or tetrahydrofurane, an aprotic polar solvent such asN,N-dimethyl- -formamide or a pair of protic-aprotic solvents such as e.g. water and an aromatic hydrocarbon (in this latter case, as a base there must be used an alkaline hydroxide). In a practical embodiment, the reaction 9 may be conducted by preparing a mixture of phosphonate I and of the ester of caronic aldehyde (V)j in a molar ratio of about 1:l and by then admixing slowly this mixture to a solution or a suspension of the base in a suitable inert solvent. In another practical form of embodiment, reaction 9 is conducted by slowly admixing a solution of phosphonate I in an inert solvent to a mixture consisting of the base, of the ester of caronic aldehyde (V) and of an inert solvent. Reaction 9 , in general, iscarried out in an anhydrous medium and under an atmosphere of an inert gas when a base there is used an alkaline metal-hydride. The lower alkyl esters of caronic aldehyde (U) are known compounds that are separable in two isomeric forms, cis and trans (isomerism on the cyclopropane ring). The possibility to use in reaction 9 also only just one of the two cis or trans forms, allows to obtain cyclopropanecarboxylic esters (q' ) having the corresponding isomerism. As far as is known to us, the only 2-alkene-phosphonate of formula I known previously, is methyl 3-chloro-2-butene-phosphonate (reaction 10). .The thus obtained esters (A') are then converted into the corresponding acyl halides, and the obtained acyl halides are reacted with alcohols of the general formula (VI) EMI8.1 wherein R5 has the above meaning. The preparation is carried out by methods known in the art, e.g by saponification of the ester into the free acid and reacting the acid with thionyl chloride Also the esterification of the acid halides with the alcohols (VI) is carried out by usual methods. The compounds of general formula A, in general, are obtained as mixtures of geometrical and configurational isomers due to the particular structure of the molecule which contains asymmetric carbon atoms and double bonds. The separation of the various mixtures in the various diastereoisomers may be achieved following the techniques usually applied in the normal practice of organic chemistry such as for instance chromatographic methods. In oder to even further illustrate this invention, in the following are given a number of examples. EXAMPLE 1 Preparation of the diethylester of 3,3-dichloro-2-propenephosphonic acid (reaction 3) EMI9.1 Into a 250 ml flask, fitted with a magnetic stirrer and a reflux condenser, there were introduced: 83 g (O.Smols) of triethylphosphiterP (OC2H,) 7 253 73 g (0.5 mols) of 1,1,3-trichloropropene Cl2CnCH-CH2Cl. The reaction mixture was stirred for 5 hours at 1600C. It was then allowed to cool down to room temperature, where after it was distilled at reduced pressure thereby gathering the fraction with boiling point comprised between 1450 and 1530C at a pressure of 24 mbar (104.7 g). The fraction thus gathered proved to consist of the product desired, having a purity of 96.6% (gas chromatographic titre GLC). IR(infrared spectroscopy),(cm-Ú):1620 (#c=c; 1260 (#P=0); 1025; 965, 920. 111 NMR (nuclear magnetic resonance): J , ppm (CDCl3,TMS) EMI9.2 1.1-1.5 (t, 6H, CH3) 2.4-3.0 (dd, 2H, CH2-P) 3.8-4.4 (m, 4H,OCH2) 5.7-6.2 (m, 1H, CCl =CH) 2 J = 7 Hz H A -H B a 7 Hz C = 22 Hz - H = 8 Hz C D (t = triplet; dd = doublet of doublet, m = multiplet; J a coupling constant EXAMPLE 2 Preparation of the diethyl ester of 3,3-dichloro-1-bromo -2-propene-phosphonic acid (reaction 2l : EMI10.1 Into a 1 litre flask, fitted with a mechanical stirrer and with a reflux condenser, closed by a calcium chloride valve, there were introduced: 125 g (0.5 mols) of diethylester of 3,3-dichloro-2-propene -phosphonic acid (obtained as described in example 28). 100 g (0.56 mols) of N-bromosuccinimide, 500 ml of carbon tetrachloride, 1.0 g of azo-bis-isobutyronitrile (A.B.N.). This mixture was then reflux heated, under constant stirring for 2 hours, after which there were admixed further 1.0 g of A.B.N. and refluxing was carried on under stirring for another 2 hours. After cooling down to OOC, the mixture was then filtered in order to remove the succinimide and from the filtrate was then evaporated the solvent. The residue was diluted in 500 ml of petroleum ether and then was cooled down to OOC. Once again there precipitated a small quantity of succinimide which was removed by filter ing. From this filtrate, after evaporation of the solvent, there was obtained a residue which was purified by chromatography on a silica gel column (eluent: petroleum ether-CH2Cl2-ethyl 22 acetate in the ratio of 10:6:4). Thereby were obtained 135 g of the desired product. The product analysis showed: IR : in agreement with the assigned structure; Elemental analysis: C, in % : theoretical: 25.75 - found : 25.43 H, in % : " 3.71 - ". 3.64 Cl,in % : " 21.75 - " 21.77 Br,in %: " 24.52 - " 25.39 P, in % : " 9.50 - " 9.22 NMR, ppm (CDCl3, TMS) EMI11.1 1.35 (t, 6H, CH ) 3 4.22 (dq, 4H, O-CH2) 4.68 (dd, 1H, CHBr) 6.16 (dd, 1H, =CH) J = 7 Hz H - H 7 Hz A B J = 8.5 Hz Hg - P B JH - HD=11.5 Hz HC - p = 11.5 Hz C = 8 Hz. H -P D (t = triplet; dq = doublet of quartet; dd = doublet of doublet; J = coupling constant). EXAMPLE 3 Preparation of the diethyl ester of 2,3,3,3-tetrachloropropane-phosphonic acid (Reaction 6) EMI12.1 Into a 500 ml flask, fitted with a mechanical stirrer, a thermometer and a reflux condenser connected with a H 2S04 valve and with one column for the separation of the gases, there were introduced: 150 ml of benzene, 24.7 g of diethyl ester of 3,3-dichloro-2-propene-phospho nic acid (prepared as described in example 1 ), 13.5 g of sulphoryl chloride. This mixture was thereupon irradiated under stirring, with an Osram "Sonne" # 300 Watt lamp, for 30 minutes, during. which the internal (inside) temperature rose to 450C showing a development of gas. After cooling down to room temperature, the solvent was eva porated at reduced pressure, thereby obtaining a residue (32 grams) consisting of the desired product. Elemental analysis: Cl, in % : theoretical: 44.60 - found : 42.63 P , in % : " 9.79 - " 9.80 IR (cm 1265, 1230, 1170, 1025, 970. EXAMPLE 4 : Preparation of the diethyl ester of 3,3,3-trichloro-1-propene-phosphonic acid: (Reaction .7) EMI13.1 Into a beaker of 300 ml holding capacity, fitted with a magnetical stirrer and a reflux condenser, closed by a calcium chloride valve, there were introduced 16 g of diethyl ester of 2,3,3,3-tetrachloropropane-phosphonic acid (prepared as described in example 3 ) : 50 ml of n-hexane; 6 ml of diethylamine. This mixture was then subjected to stirring at room temperature for 3 hours whereafter it was allowed to rest overnight. After filtering the chlorohydrate that had formed, the filtrate was washed with 10 ml of HCl 2N, then with water until obtaining a neutral pH. After anhydration with anhydrous NaZS04 and subsequent evaporation of the solvent at reduced pressure, there was obtained a residue (12.4 g) consisting of the desired product (b.p. = 840-850C at 0.11 mbar.) IR (cm ): 1635; 1260; 1210; 1165; 1020; 970; NMRJ, ppm, (CDC13, TMS): EMI14.1 1.40 (t, 6H, CH3) 4.18 (dq, 4H, CH2) 6.32 (dd, 1H, Hc) 7.10 (dd, 1H, HD) JH - H 7 Hz A B JH - p = 9 Hz B J Hc - HD = 16 Hz -P - 14.5 Hz C JH - P 20 Hz D (t = triplet; dq = doublet of quartet; dd = doublet of doublet; J = coupling constant). EXAMPLE 5 : Preparation of the diethyl ester of 1,3,3-trichloro-2-prope ne-phosphonic acid (Reaction 8) EMI14.2 Into a 100 ml beaker, fitted with a magnetical stirrer and with a reflux condenser closed by a clcium chloride valve, there were introduced: 2.8 g of diethyl ester of 3,3,3-trichloro-1-propene-phospho- nic acid (obtained as described in example 4), 1 g of CuCl2. 2H20 This mixture was thereupon stirred for 1 hour and 15 minutes at 1100C. After cooling down to room temperature, it was additioned with 100 ml of ethyl ether and then filtered. The filtrate was then washed with water until achieving the full disappearance of the green colour, after which it was anhydrified on anhydrous Na2SO4. The solvent was then evaporated under reduced pressure, thereby obtaining 25 g of the desired product (b.p. = 950-960C/0.ll mbar). Elemental analysis : C , in % : theoretical = 29.87 - found = 29.21 H , in % : " = 4.3 - " = 4.01 P , in % : " = 11.0 - " = 10.91 C1, in % : " = 37.78 - " = 36.90 -1 IR (cm-Ú) : 1615, 1270, 1025, 980, 920 NMR #, ppm (CDCl3, TMS) EMI15.1 1.39 (t, 6H, CH3) 3.85-4.50 (m, 4H, CH2) 4.7 (dd, 1H, HC) 6.08 (dd, 1H, HD) JH H 5.5 Hz A B J HC - HD = 10 - Hz JH - P = 13 Hz C JH - P = 6 Hz D D (t = triplet, m = multiplet, dd = doublet of doublet, J = coupling constant). EXAMPLE 6 : Preparation of diethyl ester of 3-chloro-2-butene-phosphonic acid. (Reaction 1) EMI16.1 Into a 100 ml flask, fitted with a magnetical stirrer and a reflux condenser, there were introduced 33.2 g (35 ml, 0.2 mols) of triethylphosphite 25 g (22 ml; 0.2 mols) of 1,3-dichloro-2-butene EMI16.2 The reaction mixture was thereupon subjected to stirring for 4 hours at 1500C, whereafter it was allowed to cool down to room temperature. Then it was distilled at reduced pressure, gathering the fraction with a b.p. of 1450-1460C at 20 mbar (37 g) and consisting of the desired product. NMR , ppm (CDCl3, TMS) EMI17.1 1.1-1.5 (t, 6H, HA) 2.0-2.2 (d, 3H, CH3-C=) 2.4-3.0 (dd, 2H, H ) C 4.0-4.3 (dq, 4H, H ) B 5.4-5.7 (m, 1H, H ) D HA -H B J = 8 Hz - P B HD Hc = 8Hz D C JH -P = 20 Hz c (d = doublet; t = triplet; dd = doublet of doublet; dq = = doublet of quadrouplet; m = multiplet, J = coupling constant). EXAMPLE 7: Preparation of O-ethyl-O-(2'-chloroethyl)-3,3-dichloro-2- -propene-phosphonate. (Reaction 2) Into a 50 ml flask, fitted with a magnetical stirrer, a thermometer, a reflux condenser and connected with a H2SO4 valve, under a nitrogen atmosphere and at room temperature, there loaded: - 14.5 g (0.1 mols) of 1,1,3-trichloro-propene - 13.5 g (0.1 mols) of 2-ethoxy-1,3,2-dioxaphospholane of the formula EMI18.1 The reaction mixture was then heated up to 1400C and then, in 2 hours and 30 minutes, the temperature was brought up to 1650C. The reaction mixture was thereupon allowed to cool down to room temperature and was then distilled at reduced pressure, gathering the fraction that distilled at between 120 and 130 C at a pressure of 0.27 mbar. The gathered fraction (15.3 g) proved to consist of the desired product showing a purity of 92% (GLC). IR (cm-Ú) : 1620 (# C=C), 1260 (# P=O), 1025, 970, 920 (# P-O-C) NMR (CDCl TMS) 3 EMI18.2 #(ppm) : 1.2-1.5 (t, 3H, CH ) 3 2.5-3.1 (dd, 2H,H B 3.6-3.8 (t, 2H, HD) D 4.0-4.5 Hz 0-4 . 5 ( (m, 4H, CH2-CH3 + H ) C 5.7-6.15 (m, lH, H ) A CH3-CH2 = 7 Hz 3HB P P 22 Hz -H = 8 Hz B A J HD - HC = 5 Hz (dd = doublet of doublet; t r triplet; m t multiplet; J = coupling constant). EXAMPLE 8 : (Preparation of Insecticides) a) Preparation of ethyl ester of 2,2-dimethyl-3-(4',4'-dichloro butadienyl)-cyclopropanecarboxylic acid (Reaction 9) EMI19.1 Into a 500 ml flask, anhydrous and maintained under a nitrogen atmosphere, there were introduced 12.5 g of a suspension of about 50% of sodium hydride (0.26 mols) in paraffine oil. This suspension was then washed with anhydrous petroleum ether (2 x 50ml) and to it were then admixed 20C ml of anhydrous dimethoxyethane. To this mixture, kept under stirring at 50-100C under a nitrogen atmosphere, there was slowly dripped,in a period of 2 hours, a mixture consisting of: - 49.5 g (0.2 mols) of diethyl ester of 3,3-dichloro-2-pro pene-phosphonic acid (obtained as de scribed in example 1 ), - 0.24 mols of ethyl ester of the caronic aldehyde (cis -trans mixture in a ratio of 58:42). Once the admixture had been accomplished, the mixture was allowed to spontaneously heat up to room temperature while keeping it under constant stirring for 1 hour. The reaction mixture was then cooled down to 100C and to it were then admixed dropwise 5 ml of ethyl alcohol and then 150 ml of a 1% hydrochloric acid. The mixture was then extracted with ethyl ether (2 x 100 ml). The reunited organic phases were then washed with water until reaching a neutral pH, anhydrified on anhydrous sodium sulphate and the solvent eliminated under reduced pressure. Thereby were obtained 76.2 g of a raw product (dark oil) which was distilled under reduced pressure thereby gathering the fraction with b.p. of 1050 - 1090C at 0.067 mbar (19 grams) consisting of the desired product (mixture of geometrical isomers) with a purity degree of 93% (GLC). Elemental analysis C , in % : theoretical = 54.77 - found = 53.77 H , in % : " = 6.13 - " = 6.18 C1, in % : " a 26.95 - " = 25.65 The IR and NMR spectroscopic data were consistent with the assigned structure. b)Preparation of the chloride of 3-(4',4'-dichlorobutadienyl) -2,2-dimethyl-cyclopropanecarboxylic acid (trans) 0.002 mols of the product, obtained as described in part a), were treated with 2.6 ml of a 10% solution of KOH in methanol. It was then reflux heated for 4 hours by a water bath. Thereafter it was cooled down and then poured into 50 ml of water. It was then extracted with toluene (2 times, each time with 20 ml of sol . vent). The organic phase was then washed with 20 ml of a 10 & NaOH. The aqueous phases were then acidified with HC1 at 5% concentration and then extracted with toluene (3 times, each time with 25 ml of solvent). The organic phase was thereupon washed with water until attaining a neutral p", whereafter it was anhydrified on sodium sulphate and then evaporated, thereby obtaining 0.4 g of an oil consisting of the desired product -1 I.R. (cm ): 3500 - -2500; 1700 - 1680; 1430; 1240; 1105; 890; 730; 690. The raw product, obtained by means of the above described reaction, was dissolved in 3.5 ml- of hexane. Then, at 00-50C, there were dripped in 3.5 m.molE of thionyl chloride. This mixture was. then subjected to reflux and stirring for 4 hours. Thereafter the hexane was decanted from the tars and evaporated at 400C under a pressure of 20 mbar, thereby obtaining about 0.2 g of chloride of 2,2-dimethyl-3-(4',4'-dichlorobutadienyl)-cy- clopropanecarboxylic acid. -1 I.R., )) (C = 0) : 1765 cm -1 ')(Cl = = CH): 1580 cm 2 9(CH = CH) : 1615 cm c) Preparation of the 4 -cyano-3-phenoxybenzyl ester of the (4)-trans-3-(4',4'-dichlorobutadienyl)-2,2-dimethyl-cyclo- propanecarboxyl ic acid. EMI21.1 0.2 g of the acrid chloride, obtained according to part b), were diluted with 1 mi of anhydrous ethylether. This mixture was cooled down to 0 C and then there was dripped into it a mixture of the cyanhidrine of phenoxybenzalde hyde (180 mg = about 0.8 m.mols) in 0.5 ml of anhydrous ether. This mixture was subjected to stirring at room temperature for 1 hour, whereafter it was cooled down to 0 C and into it was dripped a mixture consisting of 0.75 mols of pyridine and 0.5 ml of ether. Thereupon the temperature was allowed to slowly rise. The mixture was then maintained under stirring at room temperature overnight. The mixture was then diluted with 5 ml of benzene, washed with water up tb a neutral pH (2 x 5 mi), anhydrified, filtered and evaporated whereby there was obtained an oily residue of about 400 mg. Thereupon was rapidly carried out a chromatography with 20 g of silica, eluting with hexaneethyl acetate (9:1). There were obtained 200 mg of a pure product. GLC titre - 90% (glass column, length = 1.2 m, outside diameter = 6 mm, inside diameter = 4 mm; packed with Chro # 0.15-0.18 mm mosorb W.H.P./(80-100 mesh), covered with silicon oil HCC - W 982; 3.8% by weight, temperature 280 C, isothermic). NMR (CDCl3)J, ppm (TMS): 1.1-1.4 (CH3) 1.6-1.8 (m, EMI22.1 2.0-2.5 (m, EMI22.2 5.0-5.8 (m, CH = CH-CH=CCl2); I 6.2-6.5 (m, CH-CN and CH = CH - CH = CCI ); 2 6.9-7.6 (m, CH = CCl2 and aromatic protons).

Claims: CLAIMS: 1) Compounds of the general formula: EMI23.1 wherein: R r F, Cl, Br, CH3, CF3; R2 F; Cl, Br, CF; 6 3 R t H, F, Cl, Br; 7 8 R and R , equal to or different from each other, alkyl or haloalkyl with C1-C4, or R7 and R together constitute a EMI23.2 group or a EMI23.3 group, 1 that 2 provided that when R = CH3. R will be different from Cl. 2) Process for the preparation of the compounds accord ing to claim 1 , having the formula (I) wherein R6 = C1, Br, characterized in that a compound of for mul a: EMI23.4 (wherein X = Ci, Br and R1, R , R7 and R8 have the meanings indicated in claim 1) is isomerized at a temperature comprised between 200 and 150 C, in the presence of a cupric halide. 3) Process according to claim 2, characterized in that the isomerization of compound IV is achieved by stir ring of a mixture of the 'above indicated compound with the cupric halide.

Inventors: BOSONE, ENRICO, DR., CAPRARA, GIUSEPPE, CARPRIOLI, VINCENZO, CORDA, FRANCESCO, GOZZO, FRANCO, DR., MENCONI, AUGUSTO, PICCARDI, PAOLO
Applicants: MONTEDISON S.P.A.
Application year: 1980
Main classification: C07F9
IPC codes: C07C45, A01N53, C07F9, C07C17, C07C61, C07D307