Derivatives of phenyl tribromomethyl sulfone as novel compounds with potential pesticidal activity

A halogenmethylsulfonyl moiety is incorporated in numerous active herbicides and fungicides. The synthesis of tribromomethyl phenyl sulfone derivatives as novel potential pesticides is reported. The title sulfone was obtained by following three different synthetic routes, starting from 4-chlorothiophenol or 4-halogenphenyl methyl sulfone. Products of its subsequent nitration were subjected to the SNAr reactions with ammonia, amines, hydrazines and phenolates to give 2-nitroaniline, 2-nitrophenylhydrazine and diphenyl ether derivatives. Reduction of the nitro group of 4-tribromomethylsulfonyl-2-nitroaniline yielded the corresponding o-phenylenediamine substrate for preparation of structurally varied benzimidazoles.


General methods
All reactions were set up in air, and undistilled solvents were used, unless stated otherwise.
The reagents were purchased from commercial sources and were used without further purification except for Et 3 N, which was distilled from potassium hydroxide prior to use. The reported yields refer to pure isolated products, unless stated otherwise. Reactions were monitored by gas chromatography (GC) and/or thin-layer chromatography (TLC) carried out on silica-gel plates by using UV light or p-anisaldehyde solution and heat as visualizing agents. 1 H NMR spectra were recorded on a Varian Mercury 400 MHz spectrometer in CDCl 3 , using TMS (tetramethylsilane) as an internal standard; all signals are reported in ppm as (s = singlet, dd = doublet of doublets, m = multiplet, integration). IR spectra were recorded in paraffin oil on a Specord M80 Zeiss Jena spectrophotometer and reported with interpretation of significant bands. Elemental analyses were obtained by means of a Perkin Elmer 2400 apparatus. All melting points (mp) are given uncorrected.
Next, the mixture was extracted with diethyl ether twice, and the combined organic extracts were dried over Na 2 SO 4 and filtered. Ether was distilled off and the oily residue was distilled under vacuum (bp 70-72 °C / 2.66 × 10 −3 bar). Sulfide 5 was obtained in 94% yield (14.6 g, 92.4 mmol).

S4
After heating the mixture of sulfide 5 (20.15 g, 0.1275 mol) and glacial acetic acid (95 mL) to its boiling point, 30% w/w aq hydrogen peroxide (40 mL) was slowly added dropwise. The mixture was refluxed for 3 hours, and afterwards the contents of the flask were poured onto ice. The precipitate was filtered off and washed with cold water until the filtrate became neutral. Recrystallization from ethanol afforded the product 4 as a white crystalline solid (23.25 g, 0.1224 mol, 96%); mp 97-98 °C.
After cooling the mixture to ambient temperature, the precipitate was filtered off, washed with water, dried and recrystallized from 2-propanol. Product 1 was obtained in 95% yield (20.

4-Halogeno-3-nitrophenyltribromomethylsulfone 6 and 6'
Sulfone 1 (8.55 g, 0.02 mol) or 1' (9.44 g, 0.02 mol) was dissolved in concentrated (min. 95% w/w) sulfuric acid (25 mL). The mixture was heated to 60 °C and concentrated (65% w/w) nitric acid (1.7 mL, 0.025 mol HNO 3 ) was added slowly with the temperature kept below 70 °C. When the addition was finished, the mixture was heated at 80 °C for 2 hours. Then, the mixture was cooled down and poured onto crushed ice. The precipitate was filtered off, washed with water and dried. The product was purified by recrystallization from 2-propanol.

2-Nitro-4-tribromomethylsulfonylaniline 7a
To a solution of nitrosulfone 6 (23.6 g, 0.05 mol) in dioxane (200 mL) 25% w/w aqueous ammonia (100 mL) was added. After stirring the mixture for two hours at 60 °C, another portion of 25% w/w aqueous ammonia (50 mL) was added. The reaction mixture was maintained for another two hours at 60 °C. The mixture was cooled down to room temperature and concentrated in vacuo. The precipitate was filtered off, washed with water, dried and recrystallized from ethanol. Product 7a was obtained in 95% yield (21.6 g, 47.7 mmol); mp 273-275 °C.
The organic layer was dried over MgSO 4 , filtered and concentrated in vacuo. The product was recrystallized from 2-propanol.

2-Nitroaniline derivatives (7i-7k) (General procedure)
Nitrosulfone 6 (4.72 g, 0.01 mol), the appropriate aromatic amine (0.01 mol) and triethylamine (1.4 mL, 0.01 mol) were dissolved in ethanol (35 mL). The mixture was heated under reflux for 6 hours. After cooling, ethanol was evaporated under reduced pressure, and the precipitate was dissolved in dichloromethane (40 mL). The mixture was consecutively washed with 10% w/w aq HCl, water, saturated aq NaHCO 3 and water. The organic layer was dried over MgSO 4 , filtered and concentrated in vacuo. The product was recrystallized from 2propanol.
The mixture was stirred for a few minutes at room temperature and the appropriate ketone or aldehyde (0.01 mol) was added. After stirring for 30 minutes, the precipitate was filtered off, washed with water (until the water after filtration achieved a pH of 7), dried and recrystallized from 2-propanol. (9) The stirred mixture of 2-nitro-4-(tribromomethylsulfonyl)aniline (7a) (22.65 g, 0.05 mol), anhydrous stannous chloride (66.3 g, 0.35 mol) and ethanol (200 mL) was heated to 70 °C.

4-Tribromomethylsulfonyl-1,2-phenylenediamine
Then 250 mL of concentrated (35-38% w/w) hydrochloric acid was slowly added dropwise, with the temperature kept within the range of 70-75 °C. After cooling to room temperature, the precipitate was filtered off and treated with 15% w/w aqueous sodium hydroxide. The resulting residue was separated, washed with water, dried and recrystallized from ethanol.

5-Tribromomethylsulfonylbenzimidazole derivatives (11a-11e) (General procedure)
The suspension of 4-tribromomethylsulfonyl-1,2-phenylenediamine (9) (4.23 g, 0.01 mol) and the appropriate carboxylic acid (0.01 mol) in 4 M aqueous hydrochloric acid (30 mL) was stirred and heated under reflux for three hours (or six hours, in the case of the preparation of 11d and 11e). The suspension was neutralized by aqueous ammonia, filtered off, washed with water, dried and recrystallized from ethanol.

5-Tribromomethylsulfonylbenzimidazole derivatives (11f-11g) (General procedure)
To a solution of the appropriate carboxylic acid (0.01 mol) in dry xylene (20 mL), titanium tetrachloride (1.1 mL, 0.01 mol) was added under a nitrogen atmosphere. The solution was stirred and diamine 9 (4.23 g, 0.01 mol) was added. The reaction mixture was heated at 130 °C for 2 hours. After cooling to room temperature, the reaction mixture was neutralized with a saturated aqueous solution of sodium bicarbonate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with water, dried over Na 2 SO 4 and concentrated in vacuo. The residue was recrystallized from ethanol.
After cooling the reaction mixture to ambient temperature, the precipitate was filtered off and purified by washing with hot chloroform.