1,2,3,4-Tetramethylbenzene

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

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

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

Procedure: Phenylglyoxal monohydrate (304 mg, 2 mM) and 1,2,3,4-tetramethylbenzene (0.60 ml, 4 mM were dissolved in dichloroethane (5 ml), titanium tetrachloride (0.33 ml, 3 mM) was added, and reacted at room temperature for 10 minutes. Using the same procedure as in Example 1, 2',3',4',5'-tetramethylbenzoin was obtained (378.2 mg, 70.7% yield). reacted at room temperature for 10 minutes

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

Procedure: 3-Chloro-1-(2,3,4,5-tetramethyl-phenyl)-propan-1-one is prepared from 1,2,3,4-tetramethyl-benzene and 3-chloro propionyl chloride by a procedure analogous to that of Preparation 1. of Preparation 1

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

Procedure: 3-Chloro-1-(2,3,4,5-tetramethyl-phenyl)-propan-1-one is prepared from 1,2,3,4-tetramethyl-benzene and 3-chloro propionyl chloride by a procedure analogous to that of Preparation 1. of Preparation 1

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

Procedure: A mixture of 10 g of 4-chloro-1,2-dinitrobenzene, 6.5 g of 4-methoxyaniline and 16 g of 1,2,3,4-tetramethylbenzene is refluxed for 15 hours. After cooling, water is added, the mixture is extracted with AcOEt, washed with a 1N solution of HCl , with a 1N solution of NaOH and with water and dried over Na2SO4 and the solvent is evaporated off under vacuum. The residue is taken up with iso ether, a gummy insoluble material is separated off and the filtrate is chromatographed on alumina using iso ether as the eluent to give 4.6 g of the expected product after crystallization from isopropanol. M.p.=98° C. is refluxed for 15 hours After cooling the mixture is extracted with AcOEt washed with a 1N solution of HCl , with a 1N solution of NaOH and with water dried over Na2SO4 the solvent is evaporated off under vacuum a gummy insoluble material is separated off the filtrate is chromatographed on alumina using iso ether as the eluent

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

Procedure: 1-((bromomethyl)sulfinyl)-4-methylbenzene (200 mg, 0.86 mmol) of example 35 was dissolved in dry diethyl ether (6 mL) under argon atmosphere. 1,2,3,4-tetramethylbenzene (0.127 g, 1.1 eq) was added to the previous solution and then the mixture was cooled to a temperature below −60° C. After stabilizing the temperature below −60° C., trifluoromethanesulfonic anhydride (0.145 mL, 1 eq) was slowly added maintaining the same temperature. After 4 hours at −60° C., the precipitate triflate salt was isolated by filtration and dried under vacuum. 0.358 g (83%) of the desired product was obtained as a white solid. mp: 136-138° C. 1H NMR (CDCl3, 400 MHz): δ 7.81 (2H, d, J=8.4 Hz), 7.71 (1H, s), 7.46 (2H, d, J=8.2 Hz), 5.69 (2H, ABQ, J=10.0 Hz), 2.50 (3H, s), 2.43 (3H, s), 2.42 (3H, s), 2.27 (3H, s), 2.26 (3H, s). 13C NMR (CDCl3, 100 MHz): δ 146.5, 143.9, 138.9, 138.8, 136.7, 132.2, 130.6, 126.9, 120.4, 118.5, 35.2, 21.6, 20.8, 17.4, 16.88, 16.81. FT-IR (KBr): 3027, 2954, 1492, 1450, 1400, 1288, 1245, 1220, 1162, 1147, 1027 cm−1. the mixture was cooled to a temperature below −60° C was slowly added maintaining the same temperature

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

Procedure: 1-((bromomethyl)sulfinyl)-4-methylbenzene (200 mg, 0.86 mmol) of example 35 was dissolved in dry diethyl ether (6 mL) under argon atmosphere. 1,2,3,4-tetramethylbenzene (0.127 g, 1.1 eq) was added to the previous solution and then the mixture was cooled to a temperature below −60° C. After stabilizing the temperature below −60° C., trifluoromethanesulfonic anhydride (0.145 mL, 1 eq) was slowly added maintaining the same temperature. After 4 hours at −60° C., the precipitate triflate salt was isolated by filtration and dried under vacuum. 0.358 g (83%) of the desired product was obtained as a white solid. mp: 136-138° C. 1H NMR (CDCl3, 400 MHz): δ 7.81 (2H, d, J=8.4 Hz), 7.71 (1H, s), 7.46 (2H, d, J=8.2 Hz), 5.69 (2H, ABQ, J=10.0 Hz), 2.50 (3H, s), 2.43 (3H, s), 2.42 (3H, s), 2.27 (3H, s), 2.26 (3H, s). 13C NMR (CDCl3, 100 MHz): δ 146.5, 143.9, 138.9, 138.8, 136.7, 132.2, 130.6, 126.9, 120.4, 118.5, 35.2, 21.6, 20.8, 17.4, 16.88, 16.81. FT-IR (KBr): 3027, 2954, 1492, 1450, 1400, 1288, 1245, 1220, 1162, 1147, 1027 cm−1. the mixture was cooled to a temperature below −60° C was slowly added maintaining the same temperature

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

Procedure: 1-((Bromomethyl)sulfinyl)-4-methylbenzene (200 mg, 0.86 mmol) of example 35 was dissolved in dry diethyl ether (6 mL) under an argon atmosphere. 1,2,3,4-tetramethylbenzene (0.127 g, 1.1 eq) was added to the previous solution and then the mixture was cooled to a temperature below −60° C. After stabilizing the temperature, trifluoromethanesulfonic anhydride (0.145 mL, 1 eq) was slowly added maintaining the same temperature. After 30 minutes, HBF4 in diethyl ether was added (54%, 0.209 mL, 1.5 eq). The resulting suspension was stirred for 30 minutes. The precipitate tetrafluoroborate salt was isolated by filtration and dried under vacuum. 0.309 g (82%) of the desired product was obtained as a white solid. mp: 238° C. 1H NMR (DMSO-d6, 400 MHz): δ 7.98 (2H, d, J=8.4 Hz), 7.78 (1H, s), 7.58 (2H, d, J=8.2 Hz), 6.8 (2H, ABQ, J=9.08 Hz), 2.51 (3H, s), 2.42 (3H, s), 2.36 (3H, s), 2.26 (3H, s), 2.25 (3H, s). 13C NMR (DMSO-d6, 100 MHz): δ 145.7, 142.8, 138.4, 137.3, 136.8, 131.6, 130.6, 126.2, 121.4, 120.5, 35.0, 20.9, 20.4, 17.1, 16.4. FT-IR (KBr): 3048, 2967, 1494, 1446, 1392, 1284, 1261, 1218, 1195, 1085, 1051, 1031, 862 cm−1. the mixture was cooled to a temperature below −60° C was slowly added maintaining the same temperature

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

Procedure: Bromomethyl phenyl sulfoxide (1 g, 4.58 mmol) of example 32 was dissolved in dry diethyl ether (30 mL) under an argon atmosphere. 1,2,3,4-tetramethylbenzene (0.678 g, 1.09 eq) was added to the previous solution and then the mixture was cooled to a temperature below −60° C. After stabilizing the temperature, trifluoromethanesulfonic anhydride (0.77 mL, 1 eq) was added slowly, maintaining the same temperature. The mixture was stirred until the reaction was complete. After 3 hours at −60° C., HBF4 in diethyl ether was added (54%, 1.11 mL; 1.75 eq). The resulting suspension was stirred for 30 minutes. The precipitated tetrafluoroborate salt formed was isolated by filtration and dried under vacuum. 1.24 g (62%) of the desired product was obtained as a white solid. mp: 140-142° C. the mixture was cooled to a temperature below −60° C was added slowly maintaining the same temperature The resulting suspension was stirred for 30 minutes

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

Procedure: Bromomethyl phenyl sulfoxide (500 mg, 2.29 mmol) of example 32 was dissolved in dry diethyl ether (15 mL) under an argon atmosphere. 1,2,3,4-Tetramethylbenzene (339 mg, 1.09 eq) was added to the previous solution and then the mixture cooled to a temperature below −60° C. After stabilizing the temperature, trifluoromethanesulfonic anhydride (0.385 ml, 1.0 eq) was added slowly, maintaining the same temperature. The mixture was stirred until the reaction was complete. The precipitated triflate salt formed was isolated by filtration, washed with diethyl ether at 0° C. and dried under vacuum. 0.779 g (70%) of the desired product was obtained as a white solid. mp: 115-116° C. the mixture cooled to a temperature below −60° C was added slowly maintaining the same temperature

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

Procedure: Bromomethyl phenyl sulfoxide (500 mg, 2.29 mmol) of example 32 was dissolved in dry diethyl ether (15 mL) under an argon atmosphere. 1,2,3,4-Tetramethylbenzene (339 mg, 1.09 eq) was added to the previous solution and then the mixture cooled to a temperature below −60° C. After stabilizing the temperature, trifluoromethanesulfonic anhydride (0.385 ml, 1.0 eq) was added slowly, maintaining the same temperature. The mixture was stirred until the reaction was complete. The precipitated triflate salt formed was isolated by filtration, washed with diethyl ether at 0° C. and dried under vacuum. 0.779 g (70%) of the desired product was obtained as a white solid. mp: 115-116° C. the mixture cooled to a temperature below −60° C was added slowly maintaining the same temperature