Bromobenzotrifluoride

A mixture of 35 g. (0.17 mole) of p-bromobenzoic acid (p. 39) and 36 g. (0.17 mole) of phosphorus pentachloride is warmed on a steam bath until there is no more visible evidence of reaction. The resulting mixture is distilled under reduced pressure. The p-bromo-benzoyl chloride is collected at 136-138°/20 mm. and is obtained in 92% yield. The product solidifies in the receiver. 

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The Buchwald-Hartwig amination reaction has gained great interest in the last decade in both academic and industrial environments. In the work presented herein, we discuss a very interesting effect in the competitive reaction of two amines (benzophenone hydrazone and n-hexylamine) with 3-bromobenzotrifluoride. 

Figure 26.2 Heat profile and conversion of the benzophenone hydrazone and of the hexylamine for a competitive amination reaction involving 3-bromobenzotrifluoride (0.5 M), benzophenone hydrazone (0.25 M) and hexylamine (0.25 M). Temperature 90°C.

We studied the competitive amination of two amines (benzophenone hydrazone and -hexylamine) and one aryl halide (3-bromobenzotrifluoride), catalyzed by Pd(BlNAP). We showed that, when reacting alone at the same conditions, n-hexylamine is considerably more reactive and shows positive order kinetics benzophenone hydrazone shows zero order kinetics and forms a very stable intermediate, the BlNAP(Pd)Ar(amine) we also observed by NMR. During the competitive reaction of the two amines, the benzophenone hydrazone reacts first and only when it is completely consumed, the hexylamine starts to react. In this case it is the stability of the major intermediate, and not the relative reactivity, which dictates the selectivity. 

Further, we examined the Heck reaction between w-butyl acrylate and 4-bromobenzotrifluoride 5 in the presence of 2 mol% Pd clusters in a singlevessel monomode m/w oven fitted with an infrared thermometer. 100% conversion with quantitative yield to the cinnamate was obtained after 5 min irradiation at 75 W/240 °C. We then repeated the reaction under conventional heating at 240 °C. After 3.5 min a black tarry gel formed. Extraction followed by GC analysis showed only cinnamate, but the tarry material (probably acrylate polymers/oligomers) could not be analysed. These experiments show that when clusters are present different results are obtained depending whether m/w heating or conventional heating is used. In principle, this could be the result of hot spots created on the metal clusters. 

Heck coupling using conventional heating. 4-bromobenzotrifluoride (0.5 mL, 495 mM), -butylacrylate (0.5 mL, 1.0 M), KOAc (approx. 3 equiv), and nanocluster suspension (0.5 mL, 10 mM) were sealed in a 5 mL glass tube and heated (240 °C, 3.5 min) in a water-cooled oven. Workup and analysis was performed as above. 

A nontraditional type of photochromic dihetarylethenes bearing a six-membered aryl moiety was described (08T9464). Compounds 34 were prepared from 2-methyl-5-phenyl-3-thienylperfluorocyclopentene by a one-step coupling reaction with 2-bromoanisole, 2-bromotoluene, 2-bro-mobenzonitrile, and 2-bromobenzotrifluoride, respectively (Scheme 12). 

Pyrrolidinylethyl chloride p-Bromobenzotrifluoride Methyl iodide Nitrobenzene... 

Conditions were investigated to recycle and regenerate the catalyst. Since the reaction formally generates potassium bromide and boric acid, the initial approach was to wash the catalyst bed with recirculating water. Three successive cycles were run with 4-bromobenzotrifluoride by washing the catalyst with warm water (50 °C) after each cycle. Although the conversion in die first cycle was 99 % in... 

Figure 2 Suzuki coupling in a semi-continuous, fixed-bed reactor. Four cycles of reaction with 4-bromobenzotrifluoride at 50 °C. 1) fresh catalyst (initial rate, 0.22 mol/h) 2) water-washed catalyst, reagents replenished (initial rate, 0.017mol/h) 3) water-washed catalyst, fresh reaction solution (initial rate, 0.012 mol/h) 4) water-washed catalyst, hydrogen reduction, fresh reaction solution (initial rate, 0.01 mol/h).

We were interested if catalyst deactivation was substrate dependent. After an initial reaction with ethyl 4-bromobenzoate the catalyst was washed with water. However, retesting with ethyl 4-bromobenzoate lead to 33 % conversion over 22 h (25 °C) down from a conversion of 98 % after 12 h (25 °C) with the fresh catalyst. In the third cycle, the catalyst was washed with warm water, aqueous NaOH (5 %) and ethanoFwater but the conversion of the ethyl 4-bromobenzoate was only 25 % after 66 h. With 4-bromoanisole, retesting at 80 °C gave only 32 % conversion down from 85 % for the fresh catalyst. Using the same catalyst but switching to the more reactive 4-bromobenzotrifluoride (50 °C) resulted in improved conversion of 60 % after 40 h. This indicates that the catalyst is still active toward electron deficient aryl bromides but after three cycles its activity is considerably reduced. These studies show that catalyst deactivation beyond the first cycle is independent of the aryl bromide substrate. 

To determine how the solvent system effected catalyst performance, the etha-noFwater (5/1) solvent was circulated through the catalyst bed for 4 h at room temperature before adding reactants. This pretreatment resulted in 85 % conversion of 4-bromobenzotrifluoride after 12 h at 50 °C which is slower than the untreated catalyst (99 % conv, 1.8 h). Treating fresh catalyst with ethanol/water as above followed by a warm water wash for 2 h resulted in 99 % conversion of 4-bromobenzotrifluoride at 50 °C (curve 1, Figure 3). However, a reaction time of... 

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