5-Methyl-2-thiophenecarboxaldehyde → N-[(5-methylthiophen-2-yl)methylidene]hydroxylamine

To a solution of 5-methylthiophene-2-carboxaldehyde (4.0 g, 31.8 mmol; Aldrich) in EtOH (24 mL) was added a solution of hydroxylamine hydrochloride (3.28 g, 47.2 mmol; Aldrich) in water (6 mL) and then a solution of sodium acetate (5.20 g, 67.5 mmol) in water (6 mL after which the mixture heated at reflux for 1 h. The mixture, after cooling, was concentrated in vacuo, and the residue diluted with water and extracted with CH2Cl2 (25 mL×2). The combined extracts were washed with water, brine, dried (Na2SO4), filtered and concentrated. The residual oily solid was triturated with Et2O (˜20 mL) to obtain 3.4 g (76% yield) of the title compound as an off-white powder: HPLC: 1.69 min (at 254 nm); LC/MS m/z 142 (M+H); 1H NMR (500 MHz, CDCl3) δ ppm 2.53 (3H, s, CH3), 6.77 (1H, d, J=3.7 Hz, Th—H), 7.21 (1H, d, J=3.7 Hz, Th—H), 7.63 (1H, s, Th—H), 9.22 (1H, br, OH); 1H NMR (500 MHz, DMSO-d6) δ ppm 2.46 (3H, s, CH3), 6.83 (1H, dd, J=3.5, 1 Hz, Th—H), 7.26 (1H, d, J=3.5 Hz, Th—H), 7.71 (1H, s, Th—H), 11.65 (1H, s, 6-NOH); 13C NMR (125.8 MHz, CDCl3) δ ppm 15.4 (CH3), 125.0 (CH), 129.1 (C), 132.5 (CH), 141.4 (CH), 147.0 (C); HRMS (ESI) calcd for C6H8NOS (M+H) 142.0327, found 142.0327 (δ+0.3 ppm). 1H— and 13C-NMR indicated this material was predominantly one geometric isomer. The mother liquor, after concentration gave 0.79 g (18% yield) of the title compound, whose 1H-NMR indicated a ˜1:1 mixture of two geometric oxime isomers.

1. temperatureat reflux for 1 h
2. temperatureThe mixture, after cooling
3. concentrationwas concentrated in vacuo
4. additionthe residue diluted with water
5. extractionextracted with CH2Cl2 (25 mL×2)
6. washThe combined extracts were washed with water, brine
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residual oily solid was triturated with Et2O (˜20 mL)

ORD record

ord-862505a4335e47ed871c146c659c1d48

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893055B2