The process of making fipronil

Accordingly, a novel crystalline modification of fipronil, a process for its preparation, pesticidal and parasiticidal mixtures and compositions comprising it and its use for combating pests and parasites has been found. The novel crystalline modification of fipronil is defined as ???novel crystalline modification I??? throughout this application.

Also, most suprisingly, 3 other crystalline modifications of fipronil have been found, which are subject to co-pending patent applications. Especially surprising was that the present crystalline modification I of fipronil has a very similar melting point as a second crystalline modification V, both melting points lying in the range of the melting points given in the prior art (i.e. 195 to 203?? C.). Moreover, two further crystalline modifications II and IV of fipronil, as described in co-pending patent applications, undergo phase transformations during heating into the more stable forms I and V, and thus in a typical melting point measurement will give the melting points of these forms I and II. The solid forms of fipronil supplier thus are part of a very complex crystallization scenario. It can be concluded that the melting points given in the literature in no way can indicate which crystalline modification or crystalline modification mixtures were analyzed.

In T 605/02, the Technical Board of Appeal of the European Patent Authority ruled that, in the absence of a respective described preparation procedure, even the XRD pattern of a certain crystalline modification does not constitute prior art for lack of enablement. Thus, melting points given in documents published prior to the filing of this application cannot be regarded as prior art for the present invention as they do not enable the artisan to prepare the novel crystalline modification of fipronil.

The novel crystalline modification I of fipronil is present in a monoclinic crystal system having the centrosymmetric space group C2/c Suitable fipronil forms different from the crystalline modification I used in step i) are, for example, selected from amorphous fipronil or crystalline fipronil such as triclinic fipronil of the space group P-1, and also mixtures of crystalline modifications of fipronil.

The fipronil form used as starting material in step i) preferably has a purity of at least 85% by weight, in particular at least 90% by weight and especially at least 95% by weight. ???Purity??? means the absence of chemical compounds other than fipronil manufacturer .he fipronil form different from the crystalline modification I will usually be incorporated into the solvent S as a solid with mixing at a concentration and temperature where the solvent S is capable of completely dissolving the fipronil form.

In a preferred embodiment of the invention, the fipronil form is dissolved at an elevated temperature, preferably from 30 to 60?? C. and particularly preferably in the range from 40 to 50?? C. The amount of fipronil form dissolved in the solvent S depends, on the nature of the solvent S and on the dissolution temperature. The person skilled in the art will be able to determine suitable conditions by standard experiments.

In a case, where the solvent S consists of methanol, the temperature range for dissolving the china fipronil form is from 20 to 60?? C., in particular in the range of from 40 to 50?? C.

In a case, where the solvent S consists of a benzene derivative B1, especially ethyl-, di isopropyl-, n-butyl benzene, and CF3-benzene, the temperature range for dissolving the fipronil form is usually above 90?? C., preferably from 100 to 140?? C., in particular in the range of from 110 to 120C.of the process of this invention, fipronil is then crystallized. Crystallization can be effected in a customary manner, for example by cooling the solution obtained in step i), by adding a solvent which reduces the solubility (in particular by adding water), or by concentrating the solution, or by a combination of the measures mentioned above.

In one embodiment of the above described process step, the added solvent, which reduces the solubility, consists of a polar solvent P.

In a preferred embodiment, step ii) is carried out in the presence of seed crystals of the crystalline modification I.

To achieve a conversion into the crystalline modification I which is as complete as possible, the crystallization is carried out over a period (duration of crystallization) of at least 1 h, in particular at least 3 h. Duration of crystallization is understood by the person skilled in the art as meaning the period of time between the beginning of the measure which initiates crystallization and the isolation of the fipronil by separating the crystalline material from the mother liquor.

In general, the crystallization is allowed to proceed to a point where at least 60%, preferably at least 70%, in particular at least 90% by weight, for example from 80 to 90% by weight, of the fipronil employed has crystallized out.It is particularly preferred that the crystallization of fipronil is effected by adding water to the solution of fipronil obtained in step i), for example from 20 to 130% by weight, in particular from 50 to 130% by weight and especially from 100 to 130% by weight of water, based on the weight of the solvent S used for dissolving the fipronil form. The addition of water is preferably carried out over a relatively long period of time, for example over a period of from 15 min to 4 h, in particular over a period of from 0.5 h to 2 h. Preferably, the resulting mixture is continuously stirred after addition of water. The person skilled in the art will be able to determine the amount of water necessary to effect crystallization.

 
 

from:freepatentsonline