CLIAMS:1. An improved process for the preparation of a cyclopropane carboxylic acid halide derivative having formula I:

whereinX1 is halogen;
R1 and R2 are each independently selected from C1-C4 alkyl; or together with the carbon to which they are attached form a 5-membered ring selected from methylidenecyclopentane, 3-methylidenetetrahydrofuran, 3-methylidenepyrrolidine, 3- methylidenetetrahydrothiophene, 2-methylidenecyclopentanone, 3- methylidenedihydrothiophen-2(3H)-one, 3-methylidenepyrrolidin-2-one and 3- methylidenedihydrofuran-2(3H)-one; and
X and Y are each independently selected from hydrogen; halogen; C1-C4 alkyl; halogenated C1-C4 alkyl; unsubstituted or halogen- substituted aryl or phenyl; - C(O) – A – R3 wherein A is an – O -, - N – or – S – spacer group and R3 is C1-C4 alkyl or halogenated C1 - C4 alkyl;
said process comprising reacting a cyclopropane carboxylic acid derivative of formula II

with a halogenating agent comprising phosphorus trihalide in the presence of a halogen.
2. The process as claimed in claim 1, wherein said process is a continuous process.
3. The process as claimed in claim 1 or claim 2, wherein said halogen is gaseous halogen.
4. The process as claimed in claim 3, wherein said gaseous halogen is gaseous chlorine.
5. The process as claimed in any one of the preceding claims, wherein said phosphorus trihalide is selected from phosphorus trichloride, phosphorus tribromide and phosphorus triiodide.
6. The process as claimed in any one of the preceding claims, wherein X1 is a halogen selected from chlorine, bromine and iodine.
7. The process as claimed in any one of the preceding claims, wherein X and Y are each independently selected from hydrogen; halogen; and C1-C4 alkyl.
8. The process as claimed in any one of the preceding claims, wherein R1 and R2 are C1-C4 alkyl.
9. The process as claimed in any one of the preceding claims additionally comprising recovering phosphorus oxyhalide generated during the reaction.
10. The process as claimed in claim 9 additionally comprising recycling the recovered phosphorus oxyhalide into the reaction.
11. The process as claimed in any one of the preceding claims additionally comprising distilling the cyclopropane carboxylic acid halide derivative.
12. The process as claimed in claim 9, wherein said step of recovering the phosphorus oxyhalide self-solvent and distillation of cyclopropane carboxylic acid halide derivative are carried out at temperature between 100C and 500C.

13. The process as claimed in any one of the preceding claims, wherein said phosphorus trihalide and halogen are used in equimolar proportions to the starting cyclopropane carboxylic acid derivative.

14. An improved process for the preparation of a synthetic pyrethroid insecticide, said process comprising:
(a) reacting a cyclopropane carboxylic acid derivative of formula II

with a halogenating agent comprising phosphorus trihalide in the presence of a halogen to obtain a cyclopropane carboxylic acid halide derivative having formula I:

whereinX1 is halogen;
R1 and R2 are each independently selected from C1-C4 alkyl; or together with the carbon to which they are attached form a 5-membered ring selected from methylidenecyclopentane, 3-methylidenetetrahydrofuran, 3-methylidenepyrrolidine, 3- methylidenetetrahydrothiophene, 2-methylidenecyclopentanone, 3- methylidenedihydrothiophen-2(3H)-one, 3-methylidenepyrrolidin-2-one and 3- methylidenedihydrofuran-2(3H)-one; and
X and Y are each independently selected from hydrogen; halogen; C1-C4 alkyl; halogenated C1-C4 alkyl; unsubstituted or halogen- substituted aryl or phenyl; – C(O) – A – R3 wherein A is an – O –, – N – or – S – spacer group and R3 is C1-C4 alkyl or halogenated C1 - C4 alkyl; and
(b) preparing a synthetic pyrethroid insecticide via the intermediate cyclopropane carboxylic acid halide derivative prepared in step (a).
15. The process as claimed in claim 14, wherein said synthetic pyrethroid is selected from cypermethrin and permethrin. ,TagSPECI:Field of the invention:
The present invention relates to an improvedprocess for the preparation of cyclopropane carboxylic acid halides.
Background and Prior art:
Cyclopropane carboxylic acid halides are useful intermediates for the synthesis of various pyrethroid insecticides.
Synthetic pyrethroids such as cypermethrin andpermethrinare widely used insecticides. There are several processes known for the preparation of cyclopropane carboxylic acid halides in which cyclopropanecarboxylic acid is converted to cyclopropane carboxylic acid halidesusing a halogenating agent. The most commonly used halogenating agent for the preparation of cyclopropane carboxylic acid chlorides is thionyl chloride.

In the conventional process, a cyclopropane carboxylic acid derivative is reacted with thionyl chloride to yield a cyclopropane carboxylic acid halide derivative. In this reaction, sulfur dioxide and hydrochloric acid are generated which are absorbed in caustic alkali (sodium hydroxide) and water scrubber respectively. The reaction product i.e. crude cyclopropane carboxylic acid halide derivativeis heated to 1200Cto remove the dissolved thionyl chloride, sulfur dioxide and hydrochloric acid. After degassing, the mass is taken for distillation to separate cyclopropane carboxylic acid halide derivative and high boiling impurities as a residue.Distilled cyclopropane carboxylic acid halide derivative is used for the preparation of a synthetic pyrethroid insecticide and the residue is sent for incineration.
The disadvantage associated with the use of thionyl chloride as chlorinating agent is that the process requires the use of caustic soda (sodium hydroxide) for absorbing sulfur dioxide which is generated during the process. Moreover, sulfur dioxide is a known pollutant and a greenhouse gas, and therefore it is desirable to prevent its generation.
The other chlorinating agents which are commonlyused for converting cyclopropane carboxylic acidderivatives to cyclopropane carboxylic acid halide derivatives include oxalyl halide, phosphoryl halide, bis(trihalomethyl) carbonate. However, there is a need in the art for halogenating agents that enable more convenient and green conversion of cyclopropane carboxylic acid derivatives to cyclopropane carboxylic acid halide derivatives. The present invention fulfills such a need existing in the art.
CN100545144 C, discloses a process in which cyclopropane carboxylic acid halide derivatives are prepared from cyclopropane carboxylic acid derivativesusing a chlorinating agent selected from the group consisting ofphosphorus trichloride (PCl3), thionyl chloride, and bis(trichloromethyl) carbonate.
EP0494146B1, discloses a processfor the preparation of cyclopropane carboxylic acid chlorides in which a cyclopropane carboxylic acid is reacted with a complex which is prepared in-situ by reaction of dimethylformamide at 0-300C with thionyl chloride, phosphoryl chloride, oxalyl chloride, phosphorus chloride or phosgene.
The disadvantage associated with use of PCl3alone as the halogenating agent is that the yield of the end-productis low due to the formation of a polymeric by-product resulting from side reaction of polymerization. There has also been noted a formation of a residue which on contact with air catches fire. Hence, the use of PCl3 isnot commercially desirable, but is nevertheless used for want of other convenient halogenating agents.
The efficacy or activity of an insecticide depends also on the level of impurities present in the technical compound at the time of its incorporation into the commercially marketed formulation. The absence of impurities also enhances the shelf-life of the technical compound and consequently that of the formulation incorporating the technical substance. Therefore, a manufacturer of a technical compound typically conducts analytical studies to ensure that the impurities are present in the technical substance only to a negligible level. There is thus a need in the art for an improved process for the preparation of cyclopropane carboxylic acid halide derivatives that only leads to a negligible formation of impurities, particularly the polymeric impurities.
The process for manufacturing cyclopropane carboxylic acid halide derivatives involves the use of a batch process for production of many intermediates before the production of the final product. There is also a need in the art for a process that could be readily adapted to a continuous process for the preparation of cyclopropane carboxylic acid halide derivative, instead of the conventionally known batch processes.

Therefore, there is a need for animproved process for the preparation of cyclopropane carboxylic acid halide derivatives which eliminates the above described problems.
Object of the invention
It is therefore an object of the present invention to provide an improved process for the preparation ofcyclopropane carboxylic acid halide derivatives from cyclopropane carboxylic acidderivatives which overcomes at least one, more preferably more than one of the above mentioned problems associated with prior art processes.
Another object of the present invention is to provide an improved process that affords a high yield of cyclopropanecarboxylic acid halide derivatives.
Yet another object of the present invention is to provide a continuous, economicaland commercially feasible process for the preparation of cyclopropane carboxylic acid halide derivatives.
Yet another object of the present invention is to provide an improved process for the preparation of cyclopropane carboxylic acid halide derivatives that only leads to a negligible formation of impurities, particularly the polymeric impurities.
Summary of the invention
The present invention provides an improved process for the preparation of a cyclopropane carboxylic acid halide derivative having formula I:

whereinX1 is halogen;
R1 and R2 are each independently selected from C1-C4 alkyl; or together with the carbon to which they are attached form a 5-membered ring selected from methylidenecyclopentane, 3-methylidenetetrahydrofuran, 3-methylidenepyrrolidine, 3-methylidenetetrahydrothiophene, 2-methylidenecyclopentanone, 3-methylidenedihydrothiophen-2(3H)-one, 3-methylidenepyrrolidin-2-one and 3-methylidenedihydrofuran-2(3H)-one; and
X and Y are each independently selected from hydrogen; halogen; C1-C4 alkyl; halogenated C1-C4 alkyl; unsubstituted or halogen- substituted aryl or phenyl; – C(O) – A – R3 wherein A is an – O –, – N – or – S – spacer group and R3 is C1-C4 alkyl or halogenated C1- C4 alkyl;
said process comprising reacting a cyclopropane carboxylic acid derivative of formula II

witha halogenating agent comprising phosphorus trihalide in the presence of a halogen.

Detailed Description of the invention
The present inventors have surprisingly found that the use of phosphorus trihalidesas the halogenating agent in the presence of a halogen provides the product cyclopropane carboxylic acid halide derivativeswith good yield in a continuous manner, and substantially free of impurities. It has been further found that phosphorus trihalides as the halogenating agent, when used in the presence of a halogen, preferably gaseous halogen, in the preparation of cyclopropane carboxylic acid halide derivatives, lead to the generation of phosphorus oxyhalides. The generated phosphorus oxyhalides act as a self-solvent for the reaction, thereby also eliminating the need to add substantial amount of a solvent externally. Therefore, it was also found that the use of a phosphorus trihalide as the halogenating agent in the presence of a halogen substantially eliminates the presence of an externally added solvent, eliminates the generation of greenhouse gases such as sulfur dioxide thereby providing an environmentally friendly process.
Therefore, a first aspect of the invention provides an improved process for the preparation of a cyclopropane carboxylic acid halide derivative having formula I:

whereinX1 is halogen;
R1 and R2 are each independently selected from C1-C4 alkyl; or together with the carbon to which they are attached form a 5-membered ring selected from methylidenecyclopentane, 3-methylidenetetrahydrofuran, 3-methylidenepyrrolidine, 3-methylidenetetrahydrothiophene, 2-methylidenecyclopentanone, 3-methylidenedihydrothiophen-2(3H)-one, 3-methylidenepyrrolidin-2-one and 3-methylidenedihydrofuran-2(3H)-one; and
X and Y are each independently selected from hydrogen; halogen; C1-C4 alkyl; halogenated C1-C4 alkyl; unsubstituted or halogen- substituted aryl or phenyl; - C(O) – A – R3 wherein A is an – O -, - N – or – S – spacer group and R3 is C1-C4 alkyl or halogenated C1 - C4 alkyl;
said process comprising reacting a cyclopropane carboxylic acid derivative of formula II

with a halogenating agent comprising phosphorus trihalide in the presence of a halogen.
In an embodiment, X1 is a halogen selected from chlorine, bromine and iodine.
In another embodiment, X1 is chlorine or bromine, most preferably X1 is chlorine.
In an embodiment,X and Y are each independently selected from hydrogen; halogen; C1-C4 alkyl; halogenated C1-C4 alkyl; unsubstituted or halogen- substituted aryl or phenyl; - C(O) – A – R3 wherein A is an – O –, – N – or – S – spacer group and R3 is C1-C4 alkyl or halogenated C1- C4 alkyl.
Preferably,X and Y are each independently selected from hydrogen; halogen; andC1-C4 alkyl.

In an embodiment, X and Y are halogen, and most preferably X and Y are chlorine.

In an embodiment, R1 and R2 are C1-C4 alkyl, and more preferably, R1 and R2 are methyl.

In an embodiment, the process of the present invention comprises recovering phosphorus oxyhalide generated during the reaction and recycling the recovered phosphorus oxyhalide into the reaction.

In another embodiment, the process of the present invention comprises an additional step of distilling the cyclopropane carboxylic acid halide derivative to obtain the final product.

In an embodiment,the steps of recovering the phosphorus oxyhalide self-solvent and distillation of cyclopropane carboxylic acid halide derivative are carried out at temperature between 100Cand 500C. In yet another preferred embodiment, the steps of recovering the phosphorus oxyhalide self-solvent and distillation of cyclopropane carboxylic acid halide derivative are carried out at temperature of about 30 0C.

In an embodiment, the molar ratio of phosphorus trihalide andgaseous halogen is not particularly limiting and may be conveniently selected by a person skilled in the art. In a preferred embodiment, phosphorus trihalide and halogen are used in equimolar proportions to the starting cyclopropane carboxylic acid derivative.
The phosphorus trihalide is selected from phosphorus trichloride; phosphorus tribromide and phosphorus triiodide.
In an embodiment, the phosphorus trihalide is preferably phosphorus trichloride.
The halogen is selected from chlorine, bromine and iodide. Preferably, the halogen is chlorine.
In an embodiment, the halogen is preferably gaseous chlorine.
The phosphorus oxyhalide solvent is selected from phosphorus oxychloride, phosphorus oxybromide and phosphorusoxyiodide, which may be present initially in small amounts. In an embodiment, the phosphorus oxyhalide solvent is phosphorus oxychloride.
In an embodiment, phosphorus oxychloridemay be used as a solvent when the halogenating agent comprises phosphorus trichloride in the presence of chlorine gas.
In an embodiment, phosphorus oxybromidemay be used as a solvent when the halogenating agent comprises phosphorus tribromidein the presence of bromine gas.
In an embodiment, phosphorus oxyiodide may be used as a solvent when the halogenating agent comprises phosphorus triiodide in the presence of iodine gas.
In an embodiment, the recovery of phosphorus oxyhalide is carried out at a temperature between 80 and 120 0Cand at pressure upto 60 torr.
In an embodiment, the target product cyclopropane carboxylic acid halide derivative is distilled out at a temperature between 100 0Cand 1400Cand pressure of 1 - 3 torr.
The process can be carried out in a continuous manner using a reactor system comprising continuous-flow stirred-tank reactors or a plug-flow reactor.
In an embodiment, the process of the present invention enables preparation of optical isomers of cyclopropane carboxylic acid halide derivatives by using the optically active isomer of cyclopropane carboxylic acid derivatives.
The cyclopropane carboxylic acid chloride derivatives prepared by the process of the present invention can be conveniently used to prepare certain well known synthetic pyrethroid insecticides. The choice of the synthetic pyrethroid or the process used to prepare the same is not particularly limiting. The preparation of a synthetic pyrethroid using the cyclopropane carboxylic acid chloride derivatives is well known to a skilled artisan and does not form a critical part of the present invention.
Therefore, in this embodiment, the present invention provides an improved process for the preparation of a synthetic pyrethroid insecticide, said process comprising:
(a) reacting a cyclopropane carboxylic acid derivative of formula II

with a halogenating agent comprising phosphorus trihalide in the presence of a halogen to obtain a cyclopropane carboxylic acid halide derivative having formula I:

whereinX1 is halogen;
R1 and R2 are each independently selected from C1-C4 alkyl; or together with the carbon to which they are attached form a 5-membered ring selected from methylidenecyclopentane, 3-methylidenetetrahydrofuran, 3-methylidenepyrrolidine, 3- methylidenetetrahydrothiophene, 2-methylidenecyclopentanone, 3- methylidenedihydrothiophen-2(3H)-one, 3-methylidenepyrrolidin-2-one and 3- methylidenedihydrofuran-2(3H)-one; and
X and Y are each independently selected from hydrogen; halogen; C1-C4 alkyl; halogenated C1-C4 alkyl; unsubstituted or halogen- substituted aryl or phenyl; - C(O) – A – R3 wherein A is an – O -, - N – or – S – spacer group and R3 is C1-C4 alkyl or halogenated C1 - C4 alkyl; and
(b) preparing a synthetic pyrethroid insecticide via the intermediate cyclopropane carboxylic acid halide derivative prepared in step (a).
In an embodiment, the synthetic pyrethroid is cypermethrin.
In another embodiment, the synthetic pyrethroid is permethrin.
Therefore, the process of the present invention is extremely suitable for commercial production of cyclopropane carboxylic acid halides and further production of synthetic pyrethroids.
EXAMPLES
The following examples illustrate the invention and are not intended to be limiting.
EXAMPLE 1
Preparation of 3-(2,2-dichlorethenyl)-2,2-dimethyl-cyclopropane carboxylic acid chloride (DVA-Cl) from 3-(2,2-dichlorethenyl)-2,2-dimethyl-cyclopropane carboxylic acid (DVA).
Taken POCl3(165 gm) as a solvent in the glass agitated reactor and DVA (250 gm) was added slowly. After the addition of DVA added molar quantities of PCl3 to the reactor and injectedchlorine gas slowly at a rate of 21 gm/hrwhile maintaining reaction temperature at 30 0C with cooling. After the complete addition of chlorine gas, the reaction mass was maintained at 300Cfor 20-30 minutes.The free acid content was checked and when the free acid was found within acceptable limit, taken the reaction mass for POCl3 and DVA-Cl recovery. After the POCl3 recovery, added 4-5% by weighthigh boiler (dibutyl phthalate) to crude DVA-Cl and distillation was done at 1-2 torr and 120-1400C. The top product was distilled as pure DVA-Cl, which was separated and the bottom product sent for incineration.Yield 84-86%.
EXAMPLE 2
Molten DVA (0.83 mole) was dissolved in a suitable inert solvent and reacted with PCl3and Cl2 at room temperature. After the desired conversion was obtained, reaction was terminated and degassing was done to remove dissolved gases.In distillation, POCl3was recovered as a byproduct and then DVA-Cl as a main product (0.77 mole, Yield 92% - 94%) was obtained.
EXAMPLE 3 (Comparative Example)
TakencrudeDVA-Cl or POCl3 in a glass agitated reactor and added DVA (250 gm) slowly. After the addition of DVA added molar quantities of PCl3 to the reactor, keeping the reaction temperature at 300C with cooling. After the complete addition of PCl3, maintained the reaction mass at 300C for 20-30 minutes, added 4-5% by weight high boiler (dibutyl phthalate) to crude DVA-Cl and distillation done at 1-2 torr and 120-1400C. The top product distilled DVA-Cl was separated and the bottom product sent for incineration. Yield 65%.
It was thus found that the conventional process led to a much lower yield due to the undesired formation of large quantities of polymeric impurities (approx. 20-28%). In contrast, the process of the present invention afforded a substantially higher yield of DVA-Cl and a negligible formation of polymeric impurities, which was unexpected.
The invention has been described in detail with reference to preferred embodiments thereof. However, it will be appreciated by those skilled in the art that changes may be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.