2-methylbenzonitrile

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

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

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

Conditions: temp:25.01; pressure:0.00; stir:

Procedure: General procedure C was applied to 2-methylbenzonitrile 15g(47mg, 0.4mmol). The reaction mixture was stirredat room temperature for 16hours giving a conversion of >99% (GCMS) and 16g, 17gand 18in a 52:40:8 mixture (1H NMR spectrum).

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

Procedure: A mixture of 2-methyl-benzonitrile (0.950 mL, 8 μmol), hydroxylamine 50% in water (1.6 mL, 24 mmol) and EtOH (8 mL) was heated at 70° C. for 48 h TLC analysis (DCM/MeOH: 97/3 as eluent) indicates the completion of the reaction The solvent was removed under reduced pressure to afford 1.2 g of N′-hydroxy-2-methylbenzamidine (Yield: 100%) as a white powder (M.P.=147-148.5° C.) which can be used without further purification. the completion of the reaction The solvent was removed under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an oven dried 100 ml 3 neck flask equipped with septa, thermo probe and stirred bar was stirring a solution of o-tolunitrile (1 ml, 8.5 mmol) in 40 ml dry THF at 0° C. To this cold, well stirred solution was added a solution of ethylmagnesium bromide (17 ml, 17 mmol) in THF via syringe while keeping the temperature below 5° C. Removed ice bath and allowed the yellow solution to stir at ambient temperature for 24 h. The reaction was cooled to 0° C. and quenched with a solution of saturated NH4Cl (50 ml), extracted with 2× EtOAc and washed with H2O, brine, drying (MgSO4), filtration and removal of solvent in vacuo to give a crude oil. This material was chromatographed (Silica gel, 3% EtOAc/Hexane) to affort the title product. To an oven dried 100 ml 3 neck flask equipped with septa, thermo probe the temperature below 5° C Removed ice bath and allowed the yellow solution to stir at ambient temperature for 24 h quenched with a solution of saturated NH4Cl (50 ml) extracted with 2× EtOAc washed with H2O, brine drying (MgSO4), filtration and removal of solvent in vacuo to give a crude oil This material was chromatographed (Silica gel, 3% EtOAc/Hexane)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-methyl-benzonitrile (0.950 mL, 8 mmol), hydroxylamine 50% in water (1.6 mL, 24 mmol) and EtOH (8 mL) was heated at 70° C. for 48 h. TLC analysis (DCM/MeOH: 97/3 as eluent) indicates the completion of the reaction. The solvent was removed under reduced pressure to afford 1.2 g of N′-hydroxy-2-methylbenzamidine (Yield: 100%) as a white powder (M.P.=147-148.5° C.). which can be used without further purification. the completion of the reaction The solvent was removed under reduced pressure

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

Procedure: Reaction of 2-methylbenzonitrile with 1-(t-butoxy)-N,N,N′,N′-tetramethylmethanediamine to give 2-(2-dimethylaminovinyl)benzonitrile has been reported (Fisher, U. et al. Helvetica Chimica Acta, 1990, 73, 763).

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

Procedure: Reaction of 2-methylbenzonitrile with 1-(t-butoxy)-N,N,N′,N′-tetramethylmethanediamine to give 2-(2-dimethylaminovinyl)benzonitrile has been reported (Fisher, U. et al. Helvetica Chimica Acta, 1990, 73, 763).

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

Procedure: To a mixture of 301 mg (purity: 100%; 1.82 mmol) of 4-hydroxy-3,6-dichloropyridazine and 842 mg (5.59 mmol) of 2-cyclopropyl-6-methylphenol were added orthotolunitrile (2.76 g) and 325 mg (5.51 mmol) of 95% potassium hydroxide at room temperature. The resultant mixture was heated to 180° C. while stirring, and stirred at that temperature for 4 hours. Then, the resultant reaction mixture was cooled to room temperature, and a 1 N aqueous hydrochloric acid solution and methanol were added to the reaction mixture to obtain a uniform solution. The obtained solution was quantitatively determined by an HPLC internal standard analysis method, which showed that 277 mg of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (yield: 55%) and 3.2 mg of 3-chloro-6-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (yield: 0.6%) were obtained. stirred at that temperature for 4 hours Then, the resultant reaction mixture to obtain a uniform solution

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The following procedure was adapted from Zhang et al. (Org. Lett. 2008, 10, 5429-5432). To Mg turnings (1.53 g, 63.0 mmol, 1.50 equiv) in THF (50 mL) in an oven-dried round-bottom flask fitted with a reflux condenser was added 2-methyliodobenzene (11.0 g, 6.40 mL, 1.20 equiv) dropwise. The reaction mixture was heated to reflux for 1 h. To the reaction mixture was added o-tolunitrile (4.94 g, 5.00 mL, 42.2 mmol, 1.00 equiv) and the reaction mixture was heated to reflux for 22 h. The reaction mixture was cooled to 23° C. and a suspension of LiAlH4 (1.97 g, 51.9 mmol, 1.23 equiv) in THF (50 mL) was added and the reaction mixture was heated to reflux for 25 h. The reaction mixture was cooled to 23° C. and H2O (2 mL) was added dropwise. A solution of NaOH (2 mL, 1 M in H2O) was added slowly and 8 mL H2O was added. The reaction mixture was filtered through a celite pad, eluting with EtOAc, and concentrated. The residue was purified by Kugelrohr distillation (240 mTorr, 200° C.) to give di-o-tolylmethanamine as a yellow oil (8.52 g, 96% yield). The reaction mixture was heated to reflux for 1 h the reaction mixture was heated to reflux for 22 h was added the reaction mixture was heated to reflux for 25 h The reaction mixture was cooled to 23° C. The reaction mixture was filtered through a celite pad eluting with EtOAc concentrated The residue was purified by Kugelrohr distillation (240 mTorr, 200° C.)

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

Procedure: Procedure as described for Amidine X using the following amounts: 6.00 mL of 2-n-propylaniline (42.6 mmol); 21.3 mL of 2.0 M butyllithium (42.6 mmol); 5.00 g of toluonitrile (42.6 mmol). Filtration of the final pentane solution yielded 9.53 g (89%) of light yellow solid. 1H NMR (400 MHz, CDCl3): 7.76 (d, 2H), 7.22 (m, 3H), 7.15 (t, 1H), 6.99 (t, 1 H), 6.84 (d, 1 H), 4.69 (s, 2H), 2.51 (t, 2H), 2.39 (s, 3H), 1.58 (m, 2H), 0.90 (t, 3H). Filtration of the final pentane solution yielded 9.53 g (89%) of light yellow solid