1,3,5-trichlorobenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:125.01; pressure:0.00; stir:

Procedure: The general procedure A was followed using 1,3,5-trichlorobenzene (90.7 mg, 0.5 mmol) and B2pin2 (126.9 mg, 0.5 mmol, 1.0 eq.) as starting material. The resulting mixture was allowed to stir 24 hours at 125 oC. The 1H NMR conversion was 56%. 5ae was obtained as white solid (76.2 mg, 49%) after purification by silica gel flash chromatography (EtOAc/PE=1:100 v/v). m.p.: 129-131 oC.

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 100 mL pear-shaped flask were precisely weighed 0.579 g of tris[tris(dimethylamino)phosphoranylidene-amino]phosphine oxide ([(Me2N)3P=N]3P=O where Me is methyl, same in the following description) as a phosphine oxide represented by formula (1) which was substantially anhydrous by adequate drying over phosphorous pentoxide in a desiccator in vacuo (1.00 mmol) and 9.88 g of phenol (105 mmol). To the mixture warmed to 90° C. was added dropwise 15.0 g of phenyl glycidyl ether (referred to as "PGE"; same in the following description) (100 mmol) over 10 min. After addition, the mixture was stirred at the same temperature for 5 hours, and cooled to room temperature over about 10 min. A small portion of the reaction mixture was quantitatively analyzed by gas chromatography using 1,3,5-trichlorobenzene as an internal standard, indicating that the starting PGE had been almost completely consumed to form desired 1,3-diphenoxy-2-propanol in a yield of 96% based on PGE. In brief, the reaction almost quantitatively proceeded. The reaction mixture was directly subjected to column chromatography to give 22.5 g of 1,3-diphenoxy-2-propanol as a colorless solid in an isolation yield of 92% whose various analyses gave data identical to a reference standard. The catalyst activity (molar amount of a desired product per one mole of catalyst in a unit time; same in the following description) of tris[tris(dimethylamino)phosphoranylidene-amino]phosphine oxide was 20 mol/mol/h, which was surprisingly about 3, 2 or 1.5 times as large as that given by boron trifluoride, N-methylimidazole or triphenylphosphine in Comparative Example 2, 3 or 4, respectively. In a 100 mL pear-shaped flask were precisely weighed After addition cooled to room temperature over about 10 min had been almost completely consumed

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a further embodiment, the present invention relates to a method for the two step preparation of 3,5-difluoroaniline from 1,3,5-trichlorobenzene. First, an amount of 1,3,5-trichlorobenzene is reacted with a fluoride-containing compound to obtain 1,3,5-trifluorobenzene. Second, the 1,3,5-trifluorobenzene is reacted with aqueous ammonia and a metal oxide or metal hydroxide to obtain the product 3,5-difluoroaniline. containing compound

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: One embodiment of the present invention relates to the discovery that 3,5-difluoroaniline can be synthesized at high yields and high purity by fluorinating 1,3,5-trichlorobenzene in the presence of a polar solvent to make an intermediate 1,3,5-trifluorobenzene, and then aminating the 1,3,5-trifluorobenzene in the presence of aqueous or anhydrous ammonia to obtain the desired 3,5-difluoroaniline. at high yields

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triaminotrinitrobenzene is an explosive having unusual insensitivity, stability at high temperature, and respectable performance. It is insoluble in organic solvents and has a melting point above 400° C. TATB was prepared in 1887 from tribromotrinitrobenzene. It has also been prepared on a laboratory scale from 2,4,6-trinitrotoluene through selective reduction of the 4-nitro group, nitration to pentanitroaniline, and then ammonolysis. Currently, the manufacture of TATB (1) on a large scale begins with 1,3,5-trichlorobenzene (TCB, 2) which is nitrated to give 1,3,5-trichloro-2,4,6-trinitrobenzene (TCTNB, 3) as shown in FIGS. 1a and 1b hereof. The nitration step requires severe conditions of high temperature, long reaction time, and oleum, and results in significant quantities of by-products.

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4,6-Trichlorobenzaldehyde was prepared according to the procedure outlined in Synthesis 2008, 279. To a solution of 1,3,5-trichlorobenzene (10.0 g, 55.1 mmol) in THF (200 ml) at −78° C. was slowly added n-BuLi (1.6 M in hexanes, 34.4 ml, 55.1 mmol) over 20 min. The reaction mixture was stirred at −78° C. for 30 min then DMF (7.5 ml, 96.4 mmol) was added dropwise. The reaction was stirred at −78° C. for an additional 1.5 h then quenched with 3 N HCl (200 ml) and warmed to room temperature. The mixture was extracted with EtOAc. The organic layer was washed with sat NaHCO3 and brine then dried over MgSO4 and concentrated to afford 10.7 g (93%) of 2,4,6-trichlorobenzaldehyde as a white solid. 2,4,6-Trichlorobenzaldehyde was prepared outlined in Synthesis 2008, 279 at −78° C. over 20 min The reaction was stirred at −78° C. for an additional 1.5 h then quenched with 3 N HCl (200 ml) warmed to room temperature The mixture was extracted with EtOAc The organic layer was washed with sat NaHCO3 and brine then dried over MgSO4 concentrated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4,6-Trichlorobenzaldehyde was prepared according to the procedure outlined in Synthesis 2008, 279. To a solution of 1,3,5-trichlorobenzene (10.0 g, 55.1 mmol) in THF (200 ml) at −78° C. was slowly added n-BuLi (1.6 M in hexanes, 34.4 ml, 55.1 mmol) over 20 min. The reaction mixture was stirred at −78° C. for 30 min then DMF (7.5 ml, 96.4 mmol) was added dropwise. The reaction was stirred at −78° C. for an additional 1.5 h then quenched with 3 N HCl (200 ml) and warmed to room temperature. The mixture was extracted with EtOAc. The organic layer was washed with sat NaHCO3 and brine then dried over MgSO4 and concentrated to afford 10.7 g (93%) of 2,4,6-trichlorobenzaldehyde as a white solid. 2,4,6-Trichlorobenzaldehyde was prepared outlined in Synthesis 2008, 279 at −78° C. over 20 min The reaction was stirred at −78° C. for an additional 1.5 h then quenched with 3 N HCl (200 ml) warmed to room temperature The mixture was extracted with EtOAc The organic layer was washed with sat NaHCO3 and brine then dried over MgSO4 concentrated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of LDA (3 mL, 6 mmol) in THF (5 mL) was added 1,3,5-trichlorobenzene (0.91 g, 5.0 mmol) in THF (3 mL) at −78° C. under nitrogen, the resulting mixture was stirred at −78° C. for 1 h, then a solution of acetaldehyde (0.33 g, 7.5 mmol) in THF (3 mL) was added. The mixture was slowly warmed to rt. The mixture was quenched with water (10 mL), and diluted with EtOAc (50 mL). The organic phase was separated, washed with brine (10 mL), and dried over anhydrous sodium sulfate. The crude material was purified by silica gel chromatography (Hex:EtOAc=95:5→90:10) to give the title compound as a colorless oil. 1H NMR (CDCl3): δ 1.62 (d, J=6.8 Hz, 3H), 2.76 (d, J=9.9 Hz, 1H, —OH), 5.55 (m, 1H), 7.32 (s, 2H). The mixture was slowly warmed to rt The mixture was quenched with water (10 mL) diluted with EtOAc (50 mL) The organic phase was separated washed with brine (10 mL) dried over anhydrous sodium sulfate The crude material was purified by silica gel chromatography (Hex:EtOAc=95:5→90:10)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of LDA (3 mL, 6 mmol) in THF (5 mL) was added 1,3,5-trichlorobenzene (0.91 g, 5.0 mmol) in THF (3 mL) at −78° C. under nitrogen, the resulting mixture was stirred at −78° C. for 1 h, then a solution of acetaldehyde (0.33 g, 7.5 mmol) in THF (3 mL) was added. The mixture was slowly warmed to rt. The mixture was quenched with water (10 mL), and diluted with EtOAc (50 mL). The organic phase was separated, washed with brine (10 mL), and dried over anhydrous sodium sulfate. The crude material was purified by silica gel chromatography (Hex:EtOAc=95:5→90:10) to give the title compound as a colorless oil. 1H NMR (CDCl3): δ 1.62 (d, J=6.8 Hz, 3H), 2.76 (d, J=9.9 Hz, 1H, —OH), 5.55 (m, 1H), 7.32 (s, 2H). The mixture was slowly warmed to rt The mixture was quenched with water (10 mL) diluted with EtOAc (50 mL) The organic phase was separated washed with brine (10 mL) dried over anhydrous sodium sulfate The crude material was purified by silica gel chromatography (Hex:EtOAc=95:5→90:10)