P-fluorobenzoyl chloride

An analogous sequence leads to the anthelmintic agent, etibendazole (50). Reaction of the benzophenone 47, which can be obtained by acylation of g-nitroaniline with p-fluorobenzoyl chloride, with ethylene glycol leads to acetal 48. Sequential reduction of the nitro group and cyclization of the resulting diamine (49) with N,N-dicarbomethoxy-S-methyl thiourea gives the benzimidazole etibendazole (50) fl6]. 

To a cooled solution of 3-methoxy-2-pyridyl (3-D-glucopyranoside (3.2 g, 11.15 mmol) in 60 mL of dry pyridine, was added dropwise 3.1 mL (1.2 Eq.) of TBDMSOTf over 30 min at 0°C. Occasionally, it was necessary to add more TBDMSOTf to complete the reaction. After addition of 4.3 mL (36.40 mmol) of p-fluorobenzoyl chloride, the reaction mixture was kept at 0°C overnight, then poured into cold saturated NaHCOj and extracted with EtOAc. Purification by flash chromatography on silica gel using EtOAc-hexane (1 4) as the eluant gave 7.95 g of product in 93% yield mp 93°-94°C, [a]D +36.8° (c 1.6, CHC13). 

To a cooled solution of the preceding compound (70 mg, 0.066 mmol) in 1 mL of dry pyridine was added 39 p.L (0.331 mmol) of p fluorobenzoyl chloride at 0°C. After 30 min, the mixture was stirred at room temperature overnight, then it was poured into cold aqueous NaHC03, extracted with EtOAc, and the organic layer was processed as usual. Purification... 

Interestingly, only p-nitrobenzoyl chloride reacted with ethyl isocyanoacetate. Other aromatic acid chlorides, including p-chlorobenzoyl chloride, p-fluorobenzoyl chloride, and benzoyl chloride were unreactive even after 15 h at 110°C. This was attributed to marked differences in electrophilicity of the acid chlorides. The authors also considered an alternative mode of cyclization that would have produced 5-substituted 4-oxazolecarboxylic acid esters but found no evidence for these products. Selected examples are shown in Table 1.29. 

General. Pyridine is distilled from p-toluenesulfonyl chloride and then from calcium hydride and stored over potassium hydroxide. N,N-Di-methylformamide is distilled from calcium hydride and stored over molecular sieves. Dioxane is distilled from phosphorus pentoxide. Tri-n-butylamine, triethylamine, diphenyl phosphorochloridate, and o- and p-fluorobenzoyl chlorides are distilled before use. Tri-n-butylammonium pyrophosphate is prepared at room temperature according to the method of Moffatt and Khorana and stored at 5°. Paper chromatography is carried out by the descending technique on Whatman No. 1 paper in (A) isobutyric acid-1 M NH4OH (60 40) and (B) 1-propanol-water (7 3). Electrophoresis is carried out on Whatman No. 1 paper at pH 3.5 in 0.035 M citric acid-0.0148 M sodium citrate (1 1). Evaporations are carried out under reduced pressure at bath temperatures below 30°. Phosphate analyses of nucleoside triphosphates are performed by the method of Lowry and Lopez after treatment of approximately 1 / mole of these compounds for 60 min at 22° in 1 ml of Tris chloride at pH 10.4 containing 0.02 mg of alkaline phosphatase of calf intestinal mucosa (type VII, Sigma Chemical Co.). 

Preparation by reaction of p-fluorobenzoyl chloride with phenol,... 

SM was obtained by Friedel-Crafts acylation of 2,3-dichloroanisole with p-fluorobenzoyl chloride in the presence of aluminium chloride in methylene chloride first at 5°, then at reflnx for 2 h (50%) [475] or in ethylene dichloride at 60° for 1 h [476]. 

Preparation by reaction of p-fluorobenzoyl chloride with m-cresol in nitrobenzene in the presence of aluminium chloride first at 0°, then at 60° for 20 h (33%) [1105]. 

Preparation by reaction of p-fluorobenzoyl chloride with 3,4-dimethoxyphenol in the presence of boron trichloride in a benzene/ methylene chloride mixture at r.t. for 2 h [598]. 

Preparation by Friedel-Crafts acylation of o-tert-butylphenol with p-fluorobenzoyl chloride in ethylene dichloride in the presence of titanium tetrachloride, first at 0 , then at r.t. [816]. 

---