2-bromo-1-(bromomethyl)-3-methylbenzene

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

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

Procedure: A mixture of 2-brom-3-methylbenzylbromide (25 g, 0.095 mol) and potassium cyanide (16 g, 0.25 mol) in dimethylformamide (100 ml) was stirred at 90° C. for 20 h. The solvent was evaporated under reduced pressure and to the residue were added toluene and water. The organic layer was separated washed with water, separated and evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel using methylene chloride as eluent gave 8.8 g (44%) of the title compound. The solvent was evaporated under reduced pressure and to the residue were added toluene and water The organic layer was separated washed with water separated evaporated under reduced pressure Purification of the residue by column chromatography on silica gel

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

Procedure: A mixture of 2-brom-3-methylbenzylbromide (25 g, 0.095 mol) and potassium cyanide (16 g, 0.25 mol) in dimethylformamide (100 ml) was stirred at 90° C. for 20 h. The solvent was evaporated under reduced pressure and to the residue were added toluene and water. The organic layer was separated washed with water, separated and evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel using methylene chloride as eluent gave 8.8 g (44%) of the title compound. The solvent was evaporated under reduced pressure and to the residue were added toluene and water The organic layer was separated washed with water separated evaporated under reduced pressure Purification of the residue by column chromatography on silica gel

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

Procedure: To a stirred solution of 2-bromo-3-methylbenzylbromide (5.2 g, 0.0197 mol) in methanol (30 ml) was added saturated sodiumbicarbonate (5 ml) and the mixture was refluxed overnight. The mixture was neutralised with acetic acid and the solvent was evaporated under reduced pressure. Chromatography of the residue on silica gel using hexane: methylene chloride (7/3) as eluent gave 4.2 g (99%) of the title compound. the mixture was refluxed overnight the solvent was evaporated under reduced pressure

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

Procedure: All manipulations with air and moisture sensitive compounds were performed either in an atmosphere of thoroughly purified argon using a standard Schlenk technique or in a controlled atmosphere Glove Box (Vacuum Atmospheres Co.). Tetrahydrofuran (THF, Merck=Merck KGaA, Darmstadt, Germany) and diethyl ether (Merck) for synthesis were purified by distillation over LiAlH4, and stored over sodium benzophenone ketyl under an inert atmosphere; prior to use, the solvents were distilled from the benzophenone ketyl. Hydrocarbon solvents such as benzene (Merck), toluene (Merck) and hexanes (Merck) and including benzene-d6 for NMR measurements were typically distilled over CaH2, and were stored over Na/K alloy under an inert atmosphere; prior to use, the solvents were distilled from the Na/K alloy. Methylene chloride (Merck) and CCl2D2 (Cambridge Isotope) for NMR measurements were distilled and stored over CaH2 under an inert atmosphere; prior to use, the solvents were distilled from the CaH2. Benzothiophene (Aldrich), 2.5 M nBuLi in hexanes (Acros=Acros Organics), 1.6 M MeLi in ether (Acros), 3.0 M methylzinc chloride in THF (Aldrich), 1.0 M phenylmagnesium bromide in THF (Aldrich), 1.0 M p-tolylmagnesium bromide in THF (Aldrich), 1.0 M mesityl bromide in THF (Aldrich), 0.5 M 4-N,N-dimethylaminophenylmagnesium bromide in THF (Aldrich), 2-bromobenzylbromide (Aldrich), 2-chlorobenzylchloride (Merck), diethyl methylmalonate (Acros), 2-bromobenzotrifluoride (Acros), 3-bromobenzotrifluoride (Acros), 1,3-bis(trifluoromethyl)-5-bromobenzene (Aldrich), 4-tert-butylbromobenzene (Acros), 2-bromo-4-isopropylaniline (Aldrich), 2-bromo-2-methylpropanoyl bromide (Aldrich), 1-bromonaphthalene (Acros), 0.5 M ZnCl2 in THF (Aldrich), and Pd(PtBu3)2 (Strem=Strem Chemical Co.), 2-[di(tert-butyl)phosphino]-1,1′-biphenyl (Strem), ZrCl4(THF)2 (Aldrich), NaBH4 (Acros), NaBPh4 (Aldrich), anhydrous powdered AlCl3 (Merck), and dichlorodimethylsilane (Merck) were used as obtained. Solutions of Grignard reagents (2-trifluoromethylphenylmagnesium bromide, 3-trifluoromethylphenylmagnesium bromide, 4-tert-butylphenylmagnesium bromide, 1,3-bis(trifluoromethyl)-5-bromobenzene, and 1-naphthylmagnesium bromide) in THF were obtained from magnesium turnings (Aldrich) and the respective arylbromides in THF at reflux. 5-Methyl-4,5-dihydro-6H-cyclopenta[b]-thiophen-6-one [Ryabov, A. N.; Gribkov, D. V.; Izmer, V. V.; Voskoboynikov, A. Z. Organometallics 2002, 21, 2842] was prepared according to the published method. 2-Bromo-1-(bromomethyl)-3-methylbenzene [Baker, R. W.; Foulkes, M. A.; Griggs, M.; Nguyen, B. N. Tetrahedron Lett. 2002, 43, 9319] was prepared from 2-bromo-m-xylene (Acros) according to the published procedure. Pd(dba)2 was prepared from PdCl2 (Aldrich) and dibenzolidenacetone (Acros) as described in literature [Coulson, D. R. Inorg. Synth. 1972, 13, 121].

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

Procedure: 2-bromo-1-(bromomethyl)-3-methylbenzene (15 g, 0.057 mmol) and potassium cyanide (9.6 g, 0. 148 mol) were added to dimethylformamide (75 ml) and stirred at 90° C. overnight. The solvent was evaporated under reduced pressure and the residue partitioned between water (150 ml) and methylene chloride. The aqueous layer was extracted twice with methylene chloride, the organic extracts was separated, washed twice with water and was evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel using heptane:methylene chloride (3:7) as eluent gave 8.0 g (67%) of the title compound. The solvent was evaporated under reduced pressure the residue partitioned between water (150 ml) and methylene chloride The aqueous layer was extracted twice with methylene chloride the organic extracts was separated washed twice with water was evaporated under reduced pressure Purification of the residue by column chromatography on silica gel

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

Procedure: 2-bromo-1-(bromomethyl)-3-methylbenzene (15 g, 0.057 mmol) and potassium cyanide (9.6 g, 0. 148 mol) were added to dimethylformamide (75 ml) and stirred at 90° C. overnight. The solvent was evaporated under reduced pressure and the residue partitioned between water (150 ml) and methylene chloride. The aqueous layer was extracted twice with methylene chloride, the organic extracts was separated, washed twice with water and was evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel using heptane:methylene chloride (3:7) as eluent gave 8.0 g (67%) of the title compound. The solvent was evaporated under reduced pressure the residue partitioned between water (150 ml) and methylene chloride The aqueous layer was extracted twice with methylene chloride the organic extracts was separated washed twice with water was evaporated under reduced pressure Purification of the residue by column chromatography on silica gel

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

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

Procedure: A procedure similar to that described in Bull. Chem. Soc. Japan, 59, 3285–3286 (1986), fully incorporated herein by reference, was used. In a two liter round bottom flask equipped with an overhead stirrer and heating mantle was placed 2-bromo-meta-xylene (60.08 g, 0.325 mol) and carbon tetrachloride (650 ml). To this were added N-bromosuccinimide (57.78 g, 0.325 mol) and an additional 550 ml carbon tetrachloride. After stirring fifteen minutes benzoyl peroxide (0.72 g, 2.9 mmol, 0.9 mole %) was added, and the mixture was heated to reflux. After four hours the reaction was cooled, and the carbon tetrachloride was removed. The residue was taken up in 10% methylene chloride in n-hexane (600 ml) and filtered through silica (250 g). The filter cake was washed with an additional 400 ml of the in 10% methylene chloride in n-hexane. The filtrate was evaporated to give a clear liquid (74.22 g, 51% conversion by NMR). Vacuum distillation produced a fraction distilling at 72° C.–80° C. at 0.1 Torr as a water white liquid (40.62 g, 47% yield). NMR (CD2Cl2). 7.2 (m, 3H), 4.62 (s, 2H), 2.4 (s, 3H). Elemental analysis: C, 36.18%; H, 3.12%; Br, 61.14%; (theory: C, 36.40%; H, 3.06%; Br, 60.54%). In a two liter round bottom flask equipped with an overhead stirrer heating mantle was added the mixture was heated to reflux After four hours the reaction was cooled the carbon tetrachloride was removed filtered through silica (250 g) The filter cake was washed with an additional 400 ml of the in 10% methylene chloride in n-hexane The filtrate was evaporated to give a clear liquid (74.22 g, 51% conversion by NMR) Vacuum distillation produced a fraction

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

Procedure: A mixture of 2-bromo-3-methylbenzylbromide (25 g, 0.095 mol) and potassium cyanide (16 g, 0.25 mol) in dimethylformamide (100 ml) was stirred at 90° C. for 20 h. The solvent was evaporated under reduced pressure and to the residue were added toluene and water. The organic layer was separated washed with water, separated and evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel using methylene chloride as eluent gave 8.8 g (44%) of the title compound. The solvent was evaporated under reduced pressure and to the residue were added toluene and water The organic layer was separated washed with water separated evaporated under reduced pressure Purification of the residue by column chromatography on silica gel

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

Procedure: To a stirred solution of 2-bromo-3-methylbenzylbromide (5.2 g, 0.0197 mol) in methanol (30 ml) was added saturated sodiumbicarbonate (5 ml) and the mixture was refluxed overnight. The mixture was neutralised with acetic acid and the solvent was evaporated under reduced pressure. Chromatography of the residue on silica gel using hexane:methylene chloride (7/3) as eluent gave 4.2 g (99%) of the title compound. the mixture was refluxed overnight the solvent was evaporated under reduced pressure

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

Procedure: A mixture of 2-brom-3-methylbenzylbromide (25 g, 0.095 mol) and potassium cyanide (16 g, 0.25 mol) in dimethylformamide (100 ml) was stirred at 90° C. for 20 h. The solvent was evaporated under reduced pressure and to the residue were added toluene and water. The organic layer was separated washed with water, separated and evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel using methylene chloride as eluent gave 8.8 g (44%) of the title compound. The solvent was evaporated under reduced pressure and to the residue were added toluene and water The organic layer was separated washed with water separated evaporated under reduced pressure Purification of the residue by column chromatography on silica gel