Hexamethylenetetramine → 4-Chloro-2,5-dimethoxybenzaldehyde

Temperature

95 °C

(Wright et al., J. Am. Chem. Soc. 2008, 130, 16786-16790; Bloomer et al., J. Org. Chem. 1993, 58, 7906-7912.) To a stirred solution of 2-chloro-1,4-dimethoxybenzene (25.0 g, 0.145 mol, 1 equiv) and hexamethylene tetramine (20.5 g, 0.145 mol, 1 equiv) at room temperature was carefully added TFA (250 mL). The resulting yellow suspension was heated to 95° C. and allowed to stir for 5 h. After 5 h, the hot brown solution was poured into a 2 L Erlenmeyer flask containing approximately 250 g of crushed ice. To the vigorously stirred mixture was added solid NaHCO3 (243 g, 2.90 mol, 20 equiv) cautiously in 5-10 g portions over two hours. The resulting yellow precipitate was filtered through Celite, washed with water, and dissolved in Et2O. The organic layer was washed with water, brine, dried (MgSO4), filtered, and concentrated under reduced pressure to yield 29.0 g (100% yield) of the desired product as an off-white solid: Mp 109-109° C.; Rf 0.70 (EtOAc/hexanes, 3:7); IR (neat) 2941, 2874, 1664, 1601, 1575, 1497, 1478, 1461, 1389, 1269, 1213, 1023, 977 cm−1; 1H NMR (400 MHz, CDCl3) δ 10.35 (s, 1 H), 7.33 (s, 1 H), 3.87 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ 188.4, 156.1, 149.4, 130.4, 123.4, 114.5, 109.9, 56.5, 56.3; HRMS (EI+) m/z calcd for C9H9O3Cl 200.0240, found 200.02377. Characterization matches that reported by Bloomer et al. (J. Org. Chem. 1993, 58, 7906-7912.)

1. customat room temperature
2. waitAfter 5 h
3. additionthe hot brown solution was poured into a 2 L Erlenmeyer flask
4. filtrationThe resulting yellow precipitate was filtered through Celite
5. washwashed with water
6. dissolutiondissolved in Et2O
7. washThe organic layer was washed with water, brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure

ORD record

ord-879016e80f58483496d960abe84b0343

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169182B2