O-Xylene → Phthalazine

HRID 991431Notes

Reaction equation

HRID 991431 reaction equation
O=[N:2][NH2:3].Cl.C(N(CC)CC)C.[C:12]1([CH3:19])[C:13]([CH3:18])=[CH:14][CH:15]=[CH:16][CH:17]=1>>[CH:18]1[C:13]2[C:12](=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:19]=[N:3][N:2]=1

Participants

4

Reactant 3

HCID 7237O-XyleneHCID 11130Triethylamine hydrochlorideHCID 37183Nitrosamine

Product 1

HCID 9207PhthalazineYield 63%

Procedure

1,1′-Carbonyldiimidazole (2.0 g, 12.6 mmol) was added to a stirred solution of 5-methylisoxazole-3-carboxylic acid in DMF (50 ml). The solution was stirred for 0.5 h before adding the preceding hydrazine (2.63 g, 11.7 mmol). After 1 h at room temperature, the solution was poured into water and the resultant precipitate was filtered, washed with water (30 ml) and hexane (100 ml), and dried in vacuo to give the ketohydrazine (3.1 g, 79%); MS (ES+) m/e 334 [MH]+. A solution of the ketohydrazine (1.0 g, 3.0 mmol) and triethylamine hydrochloride (0.2 g, 1.45 mmol), in xylene (30 ml), was heated at reflux for 4 h. The solution was cooled to room temperature and the solvent removed in vacuo. The residue was chromatographed through silica gel, eluting with ethyl acetate, to give the title-phthalazine (0.60 g, 63%), mp 186-188° C.; 1H NMR (250 MHz, CDCl3) δ1.22-1.54 (4H, m, 2 of CH2), 1.94-2.06 (4H, m, 2 of CH2), 2.58 (3H, s, Me), 3.60 (1H, s, CH), 4.08 (1H, s, CH), 6.90 (1H, s, Ar—H); MS (ES+) m/e 316 [MH]+.

Workup

  1. temperatureat reflux for 4 h
  2. customthe solvent removed in vacuo
  3. customThe residue was chromatographed through silica gel
  4. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-9913f1aeaf764cccafb8ed6d9df03066
Source dataset
uspto-grants-2002_10
Patent number
US06465462B1

Reaction notes

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