4-Chloro-2-methylbenzonitrile

off-white crystalline

The crude oxathiazolone compound (2.0 g, 8.8 mmol) and 2-furonitrile (16 g, 170 mmol) were mixed and heated for 20 min at 190° C. in the microwave. Ten batches were combined and Kugelrohr distilled at 100° C./30 mbar to recover excess 2-furonitrile (used again in next microwave reactions). The residue was further distilled at 150° C./20 mbar to remove the nitrile by-product. The residue, 5.5 g was combined with the residue of another ten microwave reactions (4.5 g) and purified by column chromatography. The resulting 4.5 g (85percent pure by HPLC) was recrystallized from MeOH (50 mL) to give pure 3-(4-chloro-2-methylphenyl)-5-(furan-2-yl)-1, 2, 4-thiadiazole as light brown solid, 3.6 g (7.5percent yield).Chemical Formula: CC. Toluene (30 mL) and ice was added to the above copper cyanide solution and then the reaction mixture was stirred vigorously. The above diazonium salt solution was then slowly added to the reaction mixture. After the addition was complete, the reaction mixture was stirred at 0 C. for 30 minutes. The reaction mixture was then allowed to warm to room temperature (25 C.), and then stirred for another hour. The reaction mixture was then heated to 50 C. for 2 hours without stirring. The toluene phase and precipitate were then separated from the aqueous phase. To the toluene phase was added 10 mL concentrated HCl, 40 mL hot H2 O, and FeCl3.6H2 O (32 g, 0.118 mol) and this reaction mixture was then stirred overnight. The reaction mixture was then added to 200 mL H2 O. The organic phase was then extracted with toluene, dried and evaporated under reduced pressure to produce 4-chloro-2-methylbenzonitrile as a dark brown oil.A mixture of the oxathiazolone compound (170 mg, 1 mmol) and General procedure: A solution of 1-acetyl-4-acetoxy-4-phenylazo-1, 2, 3, 4-tetrahydroquinoline (8, 0.25 mmol) in dry CH2Cl2 (2 mL) was added dropwise slowly to a mixture ofnitrile 9 (0.35 mmol) and AlCl3 (0.35 mmol) in CH2Cl2 (5 mL) at -40 C under an atmosphere of nitrogen (exothermic). After stirring at this temperature for0.5 h, the reaction was allowed to warm to room temperature and stirred foradditional 1 h. Then the mixture was cooled to 0 C and extracted with H2O(1 mL 3). The combined aqueous phase was concentrated under reducedpressure and purified by reverse flash column chromatography. The collectedfractions were lyophilized to afford the respective5, 6-dihydro-4H-benzo[b][1, 2, 4]triazolo[1, 5-d][1, 4]diazepinium salt 10.For the chloride salt 10, reverse flash column chromatography conditions wereas follows: C18, acetonitrile = 5% in H2O and acetonitrile; 0.5% hydrochloricacid in H2O. For the trifluoroacetic salt 10, the reverse flash columnchromatography conditions were: C18, acetonitrile = 5% in H2O andacetonitrile; 0.5% trifluoroacetic acid in H2O.The picric salts 10 were obtained by exchanging the Cl- or CF3COO- anion bytreatment with picric acid. The following procedure was representative: 0.9-1.1%picric acid solution was added dropwise into the corresponding salt 10dissolved in H2O (1 mL) and a brown suspension appeared. The picric acidsolution was added dropwise continually until no further suspension appeared.The mixture was filtered, and the filtered cake was washed with H2O (0.5 mL 2), collected and dried in vacuum to give the picric salt 10.

Molecular Weight:151.59
XLogP3:2.9
Hydrogen Bond Acceptor Count:1
Exact Mass:151.0188769
Monoisotopic Mass:151.0188769
Topological Polar Surface Area:23.8
Heavy Atom Count:10
Complexity:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes