Process for the preparation of p-bromofluorobenzene

Abstract: Process for the production of p-bromofluorobenzene by the bromination of fluorobenzene, characterized in that the bromination is carried out with liquid bromine at temperatures below 0°C.

Description: This invention relates to a process for the preparation of p-bromofluorobenzene (hereinafter PBFB) in high yield and high purity by the bromination of fluorobenzene (hereinafter FB). More particularly, it relates to a process for the preparation of PBFB of >99.8% purity and in a yield of 98%. Background of the Invention The preparation of bromofluorobenzene by different processes has been described in the literature. Thus, the bromination of FB with excess liquid bromine catalyzed by iron filings is described by G. Schiemann et al., "Aromatic fluorine compounds. VIII. Some transformations with PBFB", Chem. Ber. 64, 1340, 1931. 80% PBFB is obtained by this method. L.N. Ferguson et al., "Bromination of Halobenzenes", J. Am. Chem. Soc., 76, 1250, 1954, describes the bromination of FB with bromine in CS 2 at 54-57°C, using AlBr 3 , giving an isomeric mixture which contains only 89.1% PBFB. JP 62 221,640 discloses a process for preparing p-bromofluorobenzene by reacting bromine with fluorobenzene in a nonaqueous liquid phase at 1:1.1-10 molar ratio in the presence of a preferably iron catalyst. The reaction is carried out at temperatures ≤ 100°C, preferably from -10°C to 80°C and it is obtained a mixture of brominated fluorobenzenes containing ≥ 80 mol% p-bromofluorobenzene and gaseous HBr. JP 62 93,244 describes a method whereby a gaseous mixture of FB, HBr, oxygen and nitrogen is heated over a Cu-Y-type zeolite at 190-200°C for 2-3 hours to give 93-98% PBFB at a conversion of 50%. EP-A-492594 discloses a process for preparing dimethylbromobenzene with a high ratio of the 3,4 isomer, comprising reacting o-xylene with bromine in complete darkness and in presence of a catalyst at temperatures between -10°C and -70°C. FR-A-2192480 discloses a process for the preparation of 4,4'-dibromo-biphenyl or 4,4'-dibromo-biphenylic ether by reacting bromine and biphenyl in the presence of liquid sulphurous anhydride at temperatures from -40°C to -5°C. JP 63 14,742 describes the reaction of bromine with FB (∼1:2.7) in the presence of iron powder at 5-40°C to yield a mixture of 1.0% o-bromofluorobenzene (hereinafter OBFB), 0.5% metabromofluorobenzene (hereinafter MBFB) and 98.5% PBFB with a low conversion of FB. An attempt to separate the isomers by melt crystallization resulted in PBFB in a purity of 99.8% but in a yield of only 17.2%. G. Olah et al., "The preparation and examination of organic fluorine compounds. XXIV. The halogenation of fluorobenzene", J. Chem. Soc., 1823-9, 1957, describes the bromination of FB with a molar ratio Br 2 /FB 0.8:1, whereby a product containing 98.2% PBFB and 1.8% OBFB was obtained after removing unreacted FB in a yield of ∼90%. This is still not a satisfactory result as the isomers cannot be separated by distillation. This method involves underbromination of the FB, which then requires the removal and recovery of unreacted FB at the end of the reaction. Also, an isomeric mixture is always obtained under these conditions. It is seen that the under-bromination according to the prior art gives mainly PBFB accompanied with small, but still excessive, amounts of OBFB and in some cases also MBFB, and generally with unsatisfactory yields. The use of excess bromine in this reaction has been described, C.M. Suter et al., "Some Fluorinated Amines of the Pressor Type", JACS, 63, 602-5 (1941). The Br 2 /FB ratio was ∼ 1.27 which converts all the OBFB, and some of the PBFB to dibromofluorobenzene (hereinafter DBFB). This mixture can be separated by fractional distillation. The reported yield in this case was 72% PBFB and > 20% DBFB and other impurities. Due to the unsatisfactory nature of the prior art, we carried out research to try to improve both the purity and the yield of PBFB. We discovered that the reaction temperature has a crucial influence on the ratio of the bromofluorobenzene isomers. Thus by lowering the temperature of the reaction we were able to increase the selectivity towards PBFB. Since very little OBFB is formed during the reaction only a very slight excess of bromine is required to convert this OBFB to DBFB by dibromination (post-reaction). The DBFB can be easily separated by fractional distillation leaving highly pure PBFB in high yields. It is a purpose of this invention to provide a simple and economical process for the preparation of highly pure PBFB, in high yields, by the bromination of FB. It is another purpose of this invention to provide a process which does not require a work-up stage, but in which the crude reaction product goes directly to fractional distillation and the distillation residues are then transferred to the next reaction. It is a still further purpose of this invention to provide such a process which does not require over-bromination, viz. can be carried out at a molar ratio of bromine to FB of about 1. It is a still further purpose of this invention to provide such a process which can be carried out with or without the presence of a solvent. It is a still further purpose of this invention to provide such a process which does not require expensive catalysts. Other purposes and advantages of the invention will appear as the description proceeds. Summary of the Invention The process according to the invention is characterized in that the bromination of fluorobenzene is carried out with liquid bromine at temperatures not higher than -20°C. The lowest convenient temperature should be used, which is between -20°C and -60°C with a solvent (in which no problems of solidification occur but in which the solvent recovery must be taken into account) The bromination is preferably carried out with a Br 2 /FB molar ratio comprised between 1.01 and 1.02. The lower the temperature used, the less OBFB will be produced and thus the less, slight excess of bromine will be required to convert it to DBFB. At the same time the lower the excess bromine, the less PBFB will be converted to DBFB and thus the higher will be the yield. The reaction temperature is thus crucial for obtaining a good yield of high purity PBFB. A satisfactory catalyst is FeCl 3 , which is used in an amount of 0.5-2% by weight with respect to the FB. The reaction can be carried out in the absence of a solvent, or in the presence of a solvent chosen from among dichloromethane (DCM) or dibromomethane (DBM). If a solvent is used, it is used in a weight ratio to the FB of 1:1. The bromine should be added to the FB at a low temperature, and the temperature of the reaction mixture should be controlled by efficient cooling to avoid any sudden increases which would lead to a decrease in selectivity. Detailed Description of Preferred Embodiments According to an embodiment of the invention, the reaction is carried out in the absence of a solvent. Fluorobenzene (FB) is introduced into a reactor provided with a stirrer. FeCl 3 , in an amount of 0.5-2% by weight of the FB, is added as a catalyst. The FB and the FeCl 3 , as well as the bromine, should be, as much as possible, free from moisture. An amount of moisture of 0.1% by weight in each reagent should be considered as a maximum. The reactor is cooled to a temperature not higher than -20°C and desirably close to the chosen reaction temperature. Thereafter, an approximately equimolar (with respect to the FB) quantity of bromine is added under effective stirring, so that the catalyst is homogeneously distributed throughout the reaction mixture. Effective cooling of the reactor is maintained during the entire reaction after which the reactor is heated to a temperature between 30 and 60°C, in a post-reaction, in order to convert the OBFB to DBFB. After the post-reaction, distillation is performed on the reaction mixture without any intermediate work-up. Highly pure PBFB is obtained in high yield. Example 1 Preparation of PFBP without solvent FB (1.92 kg, 20 mole) and anhydrous FeCl 3 powder (20 g) were placed in a 4-1 reactor equipped with an efficient stirrer, a condenser and a thermometer, and connected to a peristaltic pump. To the top of the condenser was attached a water trap (2 kg distilled water) to absorb HBr and HCl released during the reaction. The FB/FeCl 3 mixture was cooled to -20°C and bromine (3.26 kg, 20.38 mole) was fed in via the peristaltic pump over 2 hours. HBr started to evolve immediately, and the temperature rose. During the addition, the temperature was kept below -15°C. After all the bromine had been added, a sample was taken and analyzed. The reaction mixture was heated at 60°C for a further 1 hour with stirring, then another sample was taken and analyzed. The crude product was distilled under atmospheric pressure using a column 30 cm long and with a 2.2 cm diameter, filled with 0.5 cm Raschig rings. 3.4 kg pure PBFB was obtained at 153-155°C in a yield of ∼97% and a purity of ≥99.8%. The distillation residues contain FeCl 3 /FeBr 3 , PBFB and DBFB. The residues can be transferred to an additional reaction by adding FB and bromine, without the need for any additional catalyst. Example 2 Preparation of PFBP with solvent FB (0.96 kg, 10 mole), anhydrous FeCl 3 powder (10 g) and DCM (dichloromethane, 0.96 kg) were placed in a 4-1 reactor equipped with an efficient stirrer, a condenser and a thermometer, and connected to a peristaltic pump. To the top of the condenser was attached a water trap (1 kg distilled water) to absorb HBr and HCl released during the reaction. The FB/FeCl 3 mixture was cooled to -65°C and bromine (1.62 kg, 10.1 mole) was fed in via the peristaltic pump over 2 hours. HBr started to evolve, and the temperature rose. During the addition, the temperature was kept below -60°C. After all the bromine had been added, a sample was taken and analyzed. The reaction mixture was heated at 30°C for a further 2 hours with stirring, then another sample was taken and analyzed. The solvent was removed by evaporation and recovered for recycling. The crude product was distilled under atmospheric pressure using a column 30 cm long and with a 2.2 cm diameter, filled with 0.5 cm Raschig rings. 1.72 kg pure PBFB was obtained at 153-155°C in a yield of ∼98.3%, and with a purity of ≥99.8%. The distillation residues contain FeCl 3 /FeBr 3 , PBFB and DBFB, and can be recycled to an additional reaction, as above. The results of the reaction carried out at various temperatures are illustrated in Table I. Expt. no. Reaction temp., °C Composition of product before post reaction GC, area % Ratio PBFB/OBFB Composition of product after post reaction GC, area % 35968- PBFB OBFB DBFB PBFB OBFB DBFB 22 13-15 98.20 1.80 (-) 54.6 95.8 0.1 4.1 24 0-5 98.60 1.40 (-) 70.4 96.8 0.1 3.1 25 -20 to -17 99.20 0.80 (-) 124.0 97.7 0.1 2.2 35 -22 to -18 99.20 0.70 (-) 141.7 97.8 0.1 2.1 33 -45 to -38 99.57 0.33 (-) 301.5 98.6 0.1 1.3 30 -65 to -60 99.78 0.22 (-) 453.5 99.0 0.1 0.9 The data in the table shows that the PBFB/OBFB ratio, which expresses the purity of the final product, is sharply dependent on the temperature.

Claims: Process for the production of p-bromofluorobenzene by the bromination of fluorobenzene, characterized in that the bromination is carried out with liquid bromine at temperatures not higher than -20°C. Process according to claim 1, wherein the bromination is carried out at a temperature between -20°C and -60°C with a solvent. Process according to claim 2, wherein the bromination is carried out at a temperature not higher than -38°C. Process according to claim 1 characterized in that a post reaction is thereafter carried out by heating the reaction product to a temperature between 30°C and 60°C to convert the o-bromofluorobenzene to dibromofluorobenzene. Process according to claim 1, wherein the bromination is carried out with Br 2 /fluorobenzene molar ratio comprised between 1.01 and 1.02. Process according to claim 5, wherein the bromination is carried out with an approximately equimolar Br 2 /fluorobenzene ratio. Process according to claim 1, wherein the bromination is carried out in the presence of a catalyst. Process according to claim 7, wherein the catalyst is FeCl 3 . Process according to claim 7, wherein the catalyst is FeCl 3 , and is used in an amount of 0.5-2% by weight with respect to the fluorobenzene. Process according to claim 1, carried out in the absence of a solvent. Process according to claim 1, carried out in the presence of a solvent chosen from among dichloromethane, dibromomethane and the like. Process according to claim 11, wherein the solvent is used in a weight ratio to the fluorobenzene of 1:1. Process according to claim 1, wherein the bromine is added to the fluorobenzene at temperatures from 0°C to the reaction temperature. Process according to claim 1, wherein the temperature of the reaction mixture is controlled by cooling to avoid any increase thereof. Process according to claim 1, wherein the bromination is carried out under stirring.

Inventors: OREN JAKOB, OREN, JAKOB
Applicants: BROMINE COMPOUNDS LTD, BROMINE COMPOUNDS LTD.
Application year: 1996
Main classification: C07C17
IPC codes: C07C17, C07B61, B01J27, C07C25