Field of the invention

The present invention relates to an improved process for the preparation of cyclopropanecarboxylic acid ester and its derivatives in all stereochemical configuration as well as their mixtures.

Background and prior art

The cyclopropanecarboxylic acid ester are well known as pyrethroids and they are effectively active against a wide spectrum of insect species in household application, in professional pest control (PCO) and in agriculture. It's worth mentioning among the pyrethroids for household application different products containing the 2,2-dimethyl-3-(2-methylprop-1 -enyl)cyclopropane-1 -carboxylic acid moiety, the esters of which with the suitable alcohol are known as commercial products e.g Tetramethrin, D-allethrin, D-trans-allethrin, Imiprothrin, among the pyrethoids for PCO and agriculture applications different products containing a suitable halogenated cyclopropanecarboxylic acid , the ester of which with the suitable alcohol are known as commercial products e.g. λ- Cyalothrin, Deltamethrin, Cypermethrin, Transfluthrin, Fenfluthrin, Meperfluthrin, Heptafluthrin and Tefluthrin.

The preparation process is based on the condensation of the chloride of the suitable cyclopropanecarboxylic acid in the suitable stereochemical configuration or in their configuration mixtures with the suitable alcohol in the suitable stereochemical configuration or in their configuration mixtures.

In US3,268,398 tetramethrin is prepared by reacting the stereochemical mixture of 2,2-dimethyl-3-(2-methylprop-1 -enyl)cyclopropane-1 -carboxylic acid chloride with N-hydroxymethy-4-cyclohexene-1 ,2-carboximide at temperatures between

20°C and 1 10°C in the presence of a solvent and in the presence of an acid binding agent.

IN US3934023 D-allethrin is prepared by reacting the suitable stereochemical mixture of 2,2-dimethyl-3-(2-methylprop-1 -enyl)cyclopropane-1 -carboxylic acid chloride with the stereochemical mixture of 2-allyl-3-methylcyclopent-2-ene-1 - one -4 ol at temperatures between 40°C and 50°C in the presence of a solvent and in the presence of an acid binding agent. In IN236630 D-trans-allethrin is prepared by reacting the suitable stereochemical mixture of 2,2-dimethyl-3-(2-methylprop-1 -enyl)cyclopropane-1 -carboxylic acid chloride with (S)- 2-allyl-3-methylcyclopent-2-ene-1 -one -4-ol at temperatures between 50°C and 1 10°C in the presence of a solvent and in the presence of an acid binding agent.

In US4176189 (1 R)-trans Imiprothrin is prepared by reacting the suitable stereochemical component of 2,2-dimethyl-3-(2-methylprop-1 - enyl)cyclopropane-1 -carboxylic acid chloride with [2,5-dioxo-3-(prop-2- ynyl)imidazolidin-1 -yl)]methanol at temperatures between 40°C and 1 10°C in the presence of a solvent and in the presence of an acid binding agent.

In EP107296 , λ-Cyalothrin, Deltamethrin and Cypermethrin are prepared by reacting the suitable stereochemical component of the suitable starting material represented by an ethenyl halogen substituted or propenyl halogen substituted -2,2-dimethyl-cyclopropane-1 -carboxylic acid chloride with the suitable alcohol in the suitable stereochemical composition at temperatures between 40°C and 1 10°C in the presence of a solvent and in the presence of an acid binding agent. In Indian Patent 225306, a process for preparing transfluthrin is described. Specifically the process comprises two steps: step 1 ) chlorination of (+)1 R-trans- permethric acid with thionyl chloride and step 2) condensation of (+)1 R-trans- permethric acid chloride with 2,3,5,6-tetrafluorobenzyl alcohol in the presence of toluene as organic solvent.

In Indian Patent 239904 a method for the preparation of transfluthrin is described. Such a method comprises a first step of chlorinating (+)1 R-trans-permethric acid with at least one chlorinating agent to form (+)1 R-trans-permethric acid chloride, wherein such chlorinating agent can be thionyl chloride, phosphorous trichloride, phosphorous pentachloride or elemental chlorine. The first step can be carried out in the presence of a solvent. The second step is a condensing step of (+)1 R- trans-permethric acid chloride with 2,3,5,6-tetrafluorobenzyl alcohol, preferably in the of a solvent, more preferably-toluene. When the condensation step is carried out without a solvent, the patent provides for a stirring step in order to drive out the ensuing gasses. The method provides also for a further step of purifying the crude product to obtain transfluthrin. Such a purification step comprises the treatment of the crude product in a solvent, for instance through a steam distillation.

In US4,275,250 Fenfluthrin is obtained by condensation of permethric acid chloride and 2,3,4,5,6-pentafluoro benzyl alcohol by eliminating the hydrochloric acid formed during the reaction under vacuum.

In CN101580471 Meperfluthrin is obtained by condensation of 4-methoxymethyl- 2,3,5,6-tetrafluorobenzyl alcohol with (1 R)-trans-permethric acid chloride in toluene in the presence of pyridine at 20 °C.

In CN101367730 , Heptafluthrin is obtained by transesterification of a suitable alkyl 3-(3,3,3-trifluoro-1 -propenyl)-2,2-dimethylcyclopropanecarboxylate and 2,3,5,6-tetrafluoro-4-methoxymethylbenzyl alcohol in an organic solvent in the presence of titanate catalyst at 80-150°C. The used titanate catalyst is represented by the formula Ti(OR) ₄ .

In US7,312,366 Tefluthrin is prepared by condensation of Z-(1 R,3R)-3-(2-chloro- 3,3,3-trifluoro-1 -propenyl)-2,2-dimethylcyclopropancarboxylic acid chloride with 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol in toluene and with pyridine as acid acceptor.

All the above cited processes of the prior art give the formation of the suitable correspondent anhydride, that can represent a problem from a legal and practical point of view, since it is necessary to isolate it.

Summary of the invention

The applicant has surprisingly found out a process which eliminates or decreases to very low amounts the presence of the corresponding anhydride.

The invention hence concerns a process for preparing a pyrethroid of Formula (I)

(I)

wherein Xi and X2 are, independently of each other, selected from the group consisting of hydrogen, methyl, fluorine, chlorine, bromine and trifluoromethyl

with the proviso that Xi and X2 are not both hydrogen ;

Z is a group of formula (IV), (V) or (VI) :

(IV) (V) (VI)

wherein Ri is allyl or propargyl, R2 is hydrogen or methyl, n is an integer from 1 to 5, m is (5-n), Y is selected from the group consisting of hydrogen, (Ci-C ₄ )alkyl and (Ci-C4)alkoxy(Ci-C4)alkyl,

said process comprising the steps of:

a) reacting an acid chloride of Formula (I I)

where Xi and X2 have the same meaning as in Formula (I) with an alcohol of Formula (II I)

H O— z

(III)

where Z has the same meaning of Formula (I)

in a suitable organic solvent and in the presence of a nitrogen acid acceptor in a temperature range from 0°C to 40°C; and b) washing with water and/or an aqueous basic solution,

wherein a suitable amount of a polyamine (W)

H2N-(CH2)b-Ae-[(CH2)c-A-]p-(CH ₂ )d-NH2 (W)

wherein A is -NH- or -0-, b and d, are independently to each other, an integer in the range of 1 -5, c is an integer in the range of 2-5, e is an integer from 0 to1 , p is an integer in the range of 0-5, is added in step a) or b) or after step a) and before step b).

The process of the invention represents a substantial improvement in comparison with the processes of the prior art, allowing to get yields higher than 90% and very good purity of the pyrethroids finally obtained. Advantageously, the process of the invention doesn't give the formation of any anhydride allowing to improve the toxicity profile of the final pyrethroids. Specifically, the amount of the related anhydride formed according to the process of the invention is less than 0.1 % (w/w), preferably less than 0.02% (w/w), being 0.02% (w/w) represented by the LOD ( limit of detection) of the related anhydride as measured with gas-chromatography.

Without being bound to any theory the inventors deem that the use of the polyamine (W) in the process allows to solve the problem of the invention and to reach the goal of no relevant formation of anhydrides.

A further advantage of the invention, is that no column or work up is needed to eliminate the anhydride (purification) from the main product.

Detailed description of the invention

The present invention concerns a process for preparing a pyrethroid of Formula (I)

(I)

wherein Xi and X2 are, independently to each other, selected from the group consisting of hydrogen, methyl, fluorine, chlorine, bromine and trifluoromethyl with the proviso that Xi and X2 are not both hydrogen;

Z is a group of formula (IV) or (V) or (VI):

(IV) (V) (VI)

wherein Ri is allyl or propargyl , R2 IS hydrogen or methyl, n is an integer from 1 to 5, m is (5-n), Y is selected from the group consisting of hydrogen, (Ci-C ₄ )alkyl and (Ci-C4)alkoxy(Ci-C4)alkyl,

said process comprising the steps of:

a) reacting an acid chloride of Formula (II)

where Xi and X2 have the same meaning as in Formula (I) with an alcohol of Formula (III)

H O Z

(IN)

where Z has the same meaning of Formula (I)

in a suitable organic solvent and in the presence of a nitrogen acid acceptor in a temperature range from 0°C to 40°C; and

b) washing with water and/or an aqueous basic solution. wherein a suitable amount of a polyamine (W)

H2N-(CH2)b-Ae-[(CH2)c-A-]p-(CH ₂ )d-NH2 (W)

where A is -NH- or -0-, b and d, are independently to each other, an integer in the range of 1 -5, c is an integer in the range of 2-5, e is an integer from 0 to1 , p is an integer in the range of 0-5, is added in step a) or b) or after step a) and before step b).

In the present invention the definition "nitrogen acid acceptor" is intended to indicate a compound having at least one nitrogen atom and capable to capture the hydrochloric acid formed during the condensation step

The reaction of the acid chloride of formula (II) with the alcohol of formula (III) of step a) is carried out in the presence of a nitrogen acid acceptor. Such nitrogen acid acceptor is preferably selected from the group consisting of pyridine and its derivatives, trimethylamine, triethylamine. Pyridine derivatives are preferably a - picoline, β-picoline r -picoline, 2,6-lutidine, 3,5-lutidine 5-ethyl-2-methylpyridine and 2,4,6-collidine (8). As nitrogen acid acceptor pyridine is preferred.

The ratio of the acid chloride of formula (II) to the nitrogen acid acceptor is preferably in the range from 0.5 to 1 equivalents, more preferably from 0.55 to

0.90 equivalents, still more preferably from 0.55 to 0.85 equivalents.

The organic solvent of step a) is preferably selected from aliphatic solvents, cycloaliphatic solvents, chlorinated solvents, aromatic solvent and their mixtures.

Among aliphatic solvents, hexane, heptane and octane can be cited.

Among cycloaliphatic solvents, cyclohexane, cycloheptane can be cited.

Among chlorinated solvents, methylene chloride, chloroform, carbon tetrachloride can be cited.

Among aromatic solvents, toluene, xylene and mesitylene can be cited.

The solvent of step a) is more preferably toluene or cyclohexane.

In Formula (I) and in Formula (II) Xi is preferably methyl or chlorine.

In Formula (I) and in Formula (II) X2 is preferably methyl or chlorine.

In Formula (I) and in Formula (III) Z is preferably a group of Formula (IV) and of Formula (V).

When Z is a group of Formula (IV), Ri is preferably allyl or propargyl. When Z is a group of Formula (V), R2 is preferably hydrogen, n is preferably an integer 4-5, Y is preferably fluorine or methoxymethyl and m is preferably 1 .

The ratio of the acid chloride of formula (II) to the alcohol of formula (III) in step a) is preferably in the range from 0.95 to 1 .20 equivalents, more preferably from 1 .00 to 1 .15 equivalents.

The polyamine of formula (W) is

H2N-(CH2)b-Ae-[(CH2)c-A-]p-(CH ₂ )d-N H2 (W)

where A is -NH- or -0-, b and d, are independently to each other, an integer in the range of 1 -5, c is an integer in the range of 2-5, e is an integer from 0 to1 , p is an integer in the range of 0-5.

Preferred are the polyamines where A is -NH-, b and d , equal or different are integer 1 -3, c is an integer 2-3, e is an integer 0 - 1 , p is an integer 0- 1 .

More preferably the polyamine (W) is selected from

H2N- (CH2)2-0-CH ₂ )2-N H2

H2N- (CH2)3-0-CH ₂ )3-N H2

H2N- (CH2)2-0-(CH2)2-0-(CH ₂ )2-N H2

H2N- (CH2)3-0-(CH2)2-0-(CH ₂ )3-N H2

H2N- (CH2)2-0-(CH2)3-0-(CH ₂ )2-N H2

H2N- (CH2)3-0-(CH2)3-0-(CH ₂ )3-N H2

H2N- (CH2)3-0-[(CH2)2-0-]2-(CH ₂ )3-N H2

H2N- (CH2)2-NH-CH ₂ )2-N H2

H2N- (CH2)3-NH-(CH ₂ )3-N H2

H2N- (CH2)2-NH-(CH2)2-NH-(CH ₂ )2-N H2

H2N- (CH2)3-NH-(CH2)2-NH-(CH2)3-NH ₂

H2N- (CH2)3-NH-(CH ₂ )2-NH-(CH2)3-N H2, and

H2N- (CH2)3-NH-(CH2)3-NH-(CH2)3-NH ₂ The polyamine (W) is still more preferably 1 ,2-diaminoethane, 1 ,3- diaminopropane, 3,3'-oxybis-1 -propanamine or 1 ,2-bis-(3- aminopropylamino)ethane. The most preferred polyamine is 1 ,2-diaminoethane or 1 ,3-diaminopropane.

The amount of the polyamine is preferably in the range from 0.30 to 0.70 eq. with respect to the acid chloride of Formula (II), more preferably from 0.4 to 0.60 eq., still more preferably from 0.42 to 0.55 eq.

The suitable amount of a polyamine (W) is added in step a) or b) or after step a) and before step b). Therefore the polyamine can be added in the reaction step a), preferably as soon as the chloride has been added or can added at the end of the condensation reaction together with water during the washing step b).

Alternatively, the polyamine can be added after the condensation reaction of step a) and before the addition of water and/or basic aqueous solution of step b).

When the polyamine is added in step b) with the washing solution, a second washing step b) is preferably carried out.

The reaction of step is carried out in a temperature range 0°C-40°C, more preferably in a temperature range of 5°C - 30°C.

The washing step b) is carried out with water and/or with an aqueous basic solution. If needed, before the washing step, the product exiting from step a) is filtered.

In a preferred embodiment, after the addition of the chloride and the alcohol of step a) the reaction mixture is stirred for 1 -5 hrs. The addition of polyamine (W) is then carried out and then the mixture stirred for further Vz -2 hrs. The crude pyrethroid of formula (I) so obtained, is then optionally filtered and washed to eliminate the salt of the amine products.

In another embodiment, the reaction of step a) is carried out by reacting the acid chloride of formula (II) with the alcohol of formula (III) in the presence of pyridine as acid acceptor at, preferably temperatures in the range from 0- 10°C, thus stirring the mixture by heating in the range from 1 0°C to 30°C for 1 -3 hours. The addition of the polyamine (W) of step b) is preferably then carried out by stirring for further 1 /2-2 hours. The crude pyrethroid of formula (I) so obtained, is then washed as in step b) to eliminate the products deriving from the use of polyamine and evaporated u.v. to eliminate the solvent or the solvent mixtures.

Advantageously, in the preferred and more preferred embodiments the amount of the related anhydride formed according to the process of the invention is less than 0.1 % (w/w), preferably less than 0.02% (w/w), being 0.02% (w/w) represented by the LOD (limit of detection) of the related anhydride as measured with gas-chromatography. The analyses as reported in the experimental part were carried out on GC Agilent mod.6890, detector FID. The analytical parameters for the analyses are reported here below:

Capillary Column DB5-ms, 30 m x 250 μηπ, film thickness 0.25 μηι (or equivalent).

Oven: initial temp= 70°C, hold 3 min.

rate1 = 10°C/min, final temp. 200°C, final time= 1 min;

rate2= 1 °C/min, final temp. 220°C, final time= 10 min; rate3= 40°C/min, final temp. 240°C, final time= 10 min. Run Time = 57.50 minutes

Inlet: S/SL, split ratio 10:1 ; Temp.= 250°C

Carrier gas: N2 (high purity)

Mode: constant pressure; Pressure = 14.9 psi; average velocity= 33 cm/sec FID Detector: Temp.= 300°C, H2 flow= 30 ml/min, Air flow= 400 ml/min

Injection source: autosampler

Injection Volume: 1 μΙ_

The present invention is illustrated by way of examples, which, however, should not be construed to limit the scope of the invention.

Experimental part

Example 1

Synthesis of (f?S)-3-allyl-2-methyl-4-oxocyclopent-2-enyl (1 f?,3/ ^: ?)-2,2-dimethyl -

3-(2-methylprop-1 -enyl) cyclopropanecarboxylate (D-trans-allethrin)

In 1 liter three necked bottom flask with a stirrer, 51 .0 g (0.33 moles) of (f?S)-3- allyl-2-methyl-4-oxocyclopent-2-enyl-1 -ol with a purity of 99% (%w/w) were mixed with 180 ml of toluene and cooled to 5°C under nitrogen atmosphere. The solution was added with 34.5 g (0.43 moles) of pyridine and added slowly and under stirring with 65.0 g (0.34 moles) of (1 R,3R)-2,2-dimethyl-3-(2-methylprop- 1 -enyl) cyclopropane carboxylic acid chloride with a purity of 98.0% (% w/w), keeping the temperature at 5°C-10°C . After the addition, the reaction was heated to 15°-20°C under stirring for further 3 hours.

4.1 g (0.05 moles) of 1 ,3-diaminopropane were added and the reaction was maintained under stirring for further Vz hour. The reaction was then added with an acid aqueous solution (0.36 moles of HCI 33%(%w/w) in 135 ml of water), stirred and the organic phase separated off. The organic phase was then washed with water, separated and washed again with 65 ml of an aqueous solution containing 8% (% w/v) of sodium carbonate. The organic phase was separated and evaporated u.v at 40°C/ 0.2 kPa.

98.5 g of a crude product with a purity of 96.8% (% w/w) was obtained (yield 95%) whose NMR analysis is in accordance with the structure.

The amount of chrysanthemic anhydride was less than 0.02% (%w/w) by GC analysis as previously reported.

¹ H-NMR (300 MHz, CDCIs): 1 .15 (s, 2.25H), 1 .1 6 (s, 0.75H), 1 .27 (s, 2.25H), 1 .29 (s, 0.75H), 1 .41 (d, 0.25H, ³ J = 5.5 Hz), 1 .43 (d, 0.75H, ³ J = 5.5 Hz), 1 .70 - 1 .75 (m, 6H), 2.02 (s, 2.25H), 2.04 (s, 0.75H), 2.10 (dd, 1 H, ³ J = 7.7 Hz, ³ J = 5.2 Hz), 2.24 (dd, 0.75H, ² J = 18.7 Hz, ³ J = 2.0 Hz), 2.31 (dd, 0.25H, ² J = 18.7 Hz, ³ J = 2.0 Hz), 2.86 (dd, 0.25H, ² J = 18.7 Hz, ³ J = 7.3 Hz), 2.88 (dd, 0.75H, ² J = 18.7 Hz, ³ J = 6.3 Hz), 2.99 (d, 2H, ³ J = 6.4 Hz), 4.92 (dm, 1 H, ³ J = 7.5 Hz), 5.02 (m, 2H), 5.69 (m, 1 H), 5.77 (m, 1 H).

¹³ C-NMR (75 MHz, CDCIs): 13.75 (CH3), 13.87 (CH3), 18.34 (CH ₃ ), 20.24 (CH ₃ ), 20.37 (CH ₃ ), 21 .95 (CH ₃ ), 22.00 (CH ₃ ), 25.39 (CH ₃ ), 26.97 (CH ₂ ), 28.93 (Cq), 32.81 (CH), 33.01 (CH), 34.37 (CH), 34.42 (CH), 41 .46 (CH ₂ ), 41 .88 (CH ₂ ), 72.47 (CH), 72.77 (CH), 1 15.78 (CH ₂ ), 120.60 (CH), 120.67 (CH), 133.41 (CH), 135.70 (Cq), 141 .15 (Cq), 141 .22 (Cq), 1 65.76(Cq), 1 65.86 (Cq), 172.12 (Cq), 203.59 (Cq), 203.65 (Cq). Example 2

Synthesis of (S)-3-propargyl -2-methyl-4-oxocyclopent-2-enyl (1 R,3R)-2,2- dimethyl -3-(2-methylprop-1 -enyl) cyclopropanecarboxylate (prallethrin)

In 1 liter three necked bottom flask with a stirrer, 51 .2 g (0.33 moles) of (S)-3- propargyl -2-methyl-4-oxocyclopent-2-enyl-1 -ol with a purity of 98% (%w/w) were mixed with 180 ml of toluene and cooled to 5°C under nitrogen atmosphere. The solution was added with 35.0 g (0.44 moles) of pyridine and added slowly and under stirring with 65.3g (0.34moles) of (1 R,3R)-2,2-dimethyl-3-(2- methylprop-1 -enyl) cyclopropane carboxylic acid chloride with a purity of 98.0% (% w/w), keeping the temperature at 5°C-10°C. After the addition the reaction was heated to 10°-15°C under stirring for further 3 hours.

4.2 g (0.06 moles) of 1 ,3-diaminopropane were added and the reaction was maintained under stirring for further Vz hour. The reaction was then added of an acid aqueous solution (0.40 moles of HCI 33% (% w/w) in 138 ml of water), stirred and the organic phase separated off. The organic phase was the washed with water, separated and washed again with 60 ml of an aqueous solution containing 10% (% w/v) of sodium carbonate. The organic phase was separated and evaporated u.v at 40°C/ 0.2 kPa.

95.1 g of a crude product with a purity of 95.1 % (% w/w) was obtained (yield 91 .2%) whose NMR analysis is in accordance with the structure.

The amount of chrysanthemic anhydride was less than 0.02% (%w/w) by GC analysis as previously reported.

¹ H NMR (400 MHz, CDCI3): 1 .15 (s, 3H), 1 .27 (s, 3H), 1 .43 (d, 1 H, ³ J = 5.3 Hz), 1 .70 - 1 .75 (m, 6H), 2.01 (t, 1 H, ⁴ J = 2.8 Hz), 2.09 (dd, 1 H, ³ J = 7.7 Hz, ³ J = 5.4 Hz), 2.18 (d, 3H, ⁴ J = 1 .0 Hz), 2.26 (dd, 1 H, ² J = 18.8 Hz, ³ J = 2.0 Hz), 2.90 (dd, 1 H, ² J = 18.7 Hz, ³ J = 6.3 Hz), 3.15 (s br, 2H), 4.92 (dm, 1 H, ³ J = 7.7 Hz, ⁴ J 1 .4 Hz), 5.69 (ddq, 1 H, ³ J = 6.3 Hz, ³ J = 2.0 Hz, ⁴ J = 1 .0 Hz).

¹³ C NMR (100 MHz, CDCI3): 12.25 (CH ₂ ), 14.03 (CH ₃ ), 18.31 (CH ₃ ), 20.21 (CH ₃ ), 21 .90 (CH ₃ ), 25.36 (CH ₃ ), 28.97 (Cq), 32.84 (CH), 34.28 (CH), 41 .61 (CH2), 68.88 (CH), 72.61 (CH), 79.20 (Cq), 120.58 (CH), 135.70 (Cq), 138.02 (Cq), 1 66.85 (Cq), 171 .98 (Cq), 202.26 (Cq). Example 3

Synthesis of (S)-3-propargyl-2-methyl-4-oxocyclopent-2-enyl (1 R,3R)-2,2- dimethyl -3-(2-methylprop-1 -enyl) cyclopropanecarboxylate (prallethrin)

260.2 g (1 .70 moles) of (S)-3-propargyl -2-methyl-4-oxocyclopent-2-enyl-1 -ol with a purity of 98%(% w/w), 1 1 70 ml of cyclohexane, 1 80 g (2.25 moles) of pyridine were reacted at 1 0°C with 333.8 g (1 .75 moles ) of (1 R,3R)-2,2-dimethyl- 3-(2-methylprop-1 -enyl) cyclopropane carboxylic acid chloride with a purity of 98.0% (% w/w).

As soon as the acid chloride has been added, 30.0 g (0.29 moles) of N-(2- aminoethyl)-1 ,2-ethanediamine were added and the reaction was carried out for further 2 hrs and worked up as in Example 2 by using the appropriate amounts of acid aqueous solution (1 .97 moles of HCI 33.5% (%w/w) in 682 ml of water) and basic aqueous solution (8% (%w/v) of sodium carbonate).

484.3 g of a crude product with a purity of 92% (% w/w) was obtained (yield 87.3%) whose NMR analysis was in accordance with the structure as reported in Example 2

The amount of chrysanthemic anhydride was less than 0.02% (%w/w) by GC analysis as previously reported

Example 4

Synthesis of (S)-3-propargyl -2-methyl-4-oxocyclopent-2-enyl (1 R,3R)-2,2- dimethyl -3-(2-methylprop-1 -enyl) cyclopropanecarboxylate (prallethrin)

In 1 liter three necked bottom flask with a stirrer, 50.4 g (0.32 moles) of (S)-3- propargyl -2-methyl-4-oxocyclopent-2-enyl-1 -ol with a purity of 98% (%w/w) were mixed with 1 90 ml of toluene and cooled to 5°C under nitrogen atmosphere. The solution was added with 36.0 g (0.45 moles) of pyridine and added slowly and under stirring with 65.9g (0.34moles) of (1 R,3R)-2,2-dimethyl-3-(2- methylprop-1 -enyl) cyclopropane carboxylic acid chloride with a purity of 98.0% (% w/w), keeping the temperature at 5°C-1 0°C. After the addition the reaction was heated to 1 0°-1 5°C under stirring for further 3 hours.

The reaction was then added of an acid aqueous solution (0.40 moles of HCI 33% (% w/w) in 140 ml of water), stirred and the organic phase separated off. The organic phase was the washed with water and 4.0 g (0.04 moles) of N-(2- aminoethyl)-1 ,2-ethanediamine, separated and washed again with 60 ml of an aqueous solution containing 10% (% w/v) of sodium carbonate. The organic phase was separated and evaporated u.v at 40°C/ 0.2 kPa.

95.2 g of a crude product with a purity of 95.0% (% w/w) was obtained (yield 94.0 %) whose NMR analysis was in accordance with the structure.

The amount of chrysanthemic anhydride was less than 0.02% (%w/w) by GC analysis as previously reported

Example 5

Synthesis of (2,3,5, 6)-tetrafluorobenzyl-(1 R,3S)-3-(2,2-dichlorovinyl)-2,2- dimethyl-1 -cyclopropancarboxylate (Transfluthrin)

Following the same procedure described in Example 1 , 51 .2 g (0.28 moles ) of 2,3,5,6-tetrafluorobenzyl alcohol with a purity of 99%(% w/w), 200 ml of toluene, 28.5 g (0.36 moles) of pyridine were reacted at 10°C with 68.5 g (0.30 moles) of 1 R-trans permethric acid chloride with a purity of 99.3% (% w/w) keeping the temperature at 5°C-10°C . After the addition the reaction was heated to 10°-15°C under stirring for further 3 hours. 3.5 g (0.05 moles) of dipropylenetriamine were added and the reaction was carried out as in Example 2 using the appropriate amounts of acid aqueous solution (0.36 moles of HCI 33% (%w/w) in 125 ml of water) and 70 ml of 8% (%w/v) aqueous solution of sodium carbonate. After evaporation u.v at 40°C/ 0.2 kPa, 102.6g of a crude product with a purity of 98.8% was obtained (yield 97.6%) whose NMR analysis was in accordance with the structure.

The amount of permethric anhydride was less than 0.02% (% w/w) by GC analysis as previously reported.

¹ H-NMR (400 MHz, CDCb): 1 .18 (s, 3H ), 1 .28 (s, 3H ); 1 .60 (d, 1 H, ³ J = 5.2 Hz), 2.25 (dd, 1 H, ³ J = 8.4 Hz, ³ J = 5.2 Hz ), 5.24 (s, 2H ), 5.58 (d, 1 H, ³ J = 8.4 Hz ), 7.10 (m, 1 H ).

¹³ C-NMR (100 MHz, CDCIs): 19.96 (CH ₃ ), 22.46 (CH ₃ ), 29.34 (Cq ), 33.17 (CH), 34.28 (CH ), 53.80 (CH ₂ ), 106.71 (CH, ² J(C,F) = 22 Hz ), 1 15.17 (Cq, ² J(C,F) = 17 Hz ), 122.36 (Cq ), 126.61 (CH ), 144.05 (Cq, ¹ J(C,F) = 59 Hz, ² J(C,F) = 18 Hz ), 146.54 (Cq, ¹ J(C,F) = 54 Hz, ² J(C,F) = 23 Hz ), 170.38 (Cq) Example 6

Synthesis of [2,3,5, 6-tetrafluoro-4-(methoxymethyl)benzyl-(1 R,3S)-3-(2,2- dichlorovinyl)-2,2-dimethylcyclopropane-1 -carboxylate (Meperfluthrin)

Following the same procedure described in Example 1 , 2.0 g (8.83 mmoles) of 4-methoxymethyl-2,3,5,6 tetrafluorobenzyl alcohol, with a purity of 99% (% w/w), 16 ml of toluene, and 1 .20 g (15.02 mmole) of pyridine were reacted at 20°C- 25°C with 2.3 g( 9.91 mmoles) of 1 R-trans permethric acid chloride with a purity of 98.9% (% w/w). After the addition the reaction was maintained at to 20°-25°C under stirring for further Vz hour. 0.1 1 g (1 .47 mmoles) of dipropylenetriamine were added and the reaction was carried out as in Example 1 using the appropriate amounts of acid aqueous solution (27.1 6 mmoles of HCI 33% (%w/w) in 9.5 ml of water) and 4 ml of 8% (%w/v) aqueous solution of sodium carbonate. After evaporation u.v at 40°C/ 0.2 kPa, 3.6 g of a crude product with a purity of 97% was obtained (yield 96%) whose NMR analysis is in accordance with the structure.

The amount of permethric anhydride was less than 0.02% (%w/w) by GC analysis as previously reported.

¹ H-NMR (400 MHz, CDCI3): 1 .17 (s, 3H), 1 .27 (s, 3H ); 1 .59 (d, 1 H, ³ J = 5.2 Hz), 2.24 (dd, 1 H, ³ J = 8.4 Hz, ³ J = 5.2 Hz ), 3.39 (s, 3H ), 4.57 (s, 2H ), 5.23 (s, 2H), 5.58 (d, 1 H, ³ J = 8.4 Hz ).

¹³ C-NMR (100 MHz, CDCI3): 19.94 (CH ₃ ), 22.42 (CH3), 29.32 (Cq,), 33.1 6 (CH), 34.27 (CH), 53.69 (CH ₂ ), 58.46 (CH3), 61 .36 (CH ₂ ), 1 14.63 (Cq, ² J(C,F) = 1 6.9 Hz), 1 1 6.95 (Cq, ² J(C,F) =17.1 Hz), 122.29 (Cq), 126.63 (CH), 145.09 (Cq, ² J(C,F) =246.7 Hz), 170.33 (Cq).

Example 7

Synthesis of 2,3,5, 6-tetrafluoro-4-(methoxymethyl)benzyl-1 RS,3RS;1 RS,3SR)-

2,2-dimethyl-3-[(1 Z)-3,3,3-trifluoroprop-1 -enyl]-cyclopropanecarboxylate

(Heptafluthrin)

Following the same procedure described in Example 1 , 2.0 g (8.83 mmoles) of 4-methoxymethyl-2,3,5,6 tetrafluorobenzyl alcohol, with a purity of 99% (% w/w), 16 ml of toluene, and 1 .30 g (1 6.27 mmoles) of pyridine were reacted at 20°C- 25°C with 2.2 g( 9.22 mmoles) of (1 RS,3RS;1 RS,3SR)-2,2-dimethyl-3-[(1 2)- 3,3,3-trifluoroprop-1 -enyl]-cyclopropanecarboxylic acid chloride with a purity of 95% (% w/w). After the addition the reaction was maintained at to 20°-25°C under stirring for further 1 hour. 0.1 1 g (1 .47 mmoles) of dipropylenetriamine were added and the reaction was carried out as in Example 1 using the appropriate amounts of acid aqueous solution (28.97 mmoles of HCI 33% (%w/w) in 10 ml of water) and 13 ml of 8% (%w/v) aqueous solution of sodium carbonate. After evaporation u.v at 40°C/ 0.2 kPa, 3.65 g of a crude product with a purity of 97% was obtained (yield 96%) whose NMR analysis is in accordance with the structure.

The amount of (1 RS,3RS;1 RS,3SR)-2,2-dimethyl-3-[(1 2)-3,3,3-trifluoroprop-1 - enyl] -cyclopropanecarboxylic anhydride was less than 0.02% (%w/w) by GC analysis as previously reported.

¹ H-NMR (400 MHz, CDCI3): 1 .18 (s, 3H), 1 .27 (s, 3H); 1 .67 (d,

0.8H, ³ J = 5.2 Hz), 1 .85 (d, 0.2H, ³ J = 3.2 Hz), 2.41 -2.45 (m, 0.8H),

2.78 - 2.88 (m, 0.2H), 3.39 (s, 3H), 4.57(s, 2H), 5.24 (s, 2H), 5.23 - 5.69 (m, 2H ).

¹³ C-NMR (100 MHz, CDCI3): 20.02 (CH ₃ ), 21 .96 (CH ₃ ), 30.13 (Cq), 31 .50(CH), 35.69 (CH), 53.65 (CH2), 58.43 (CH3), 61 .33 (CH2), 1 14.63 (Cq, ² J(C,F) = 1 6.6 Hz), 1 1 6.97 (Cq, ² J(C,F) =17.6 Hz), 120.39 (CH, ² J(C,F) = 33.7 Hz), 123.13 (Cq, ¹ J(C,F) = 269.8 Hz), 138.96 (CH, ³ J (C,F) = 5.4 Hz), 145.10 (Cq, ¹ J (C,F) = 246.6Hz), 170.08 (Cq).