3-CHLORO-5-METHOXYBENZALDEHYDE

3, 5-Dichloroanisole (74.0 g, 419 mmol) in THF (200 mL) was added dropwise to magnesium metal (14.2 g, 585 mmol, pre-washed with 0.5 N HCl) in THF (100 mL) at 25° C. 3, 5-Dichloroanisole (74.0 g, 419 mmol) in THF (200 [ML)] was added dropwise to magnesium metal (14.2 g, 585 mmol, pre-washed with 0.5 N [HC1)] in THF (100 [ML)] at [25°C.] After the addition, 1, 2-dibromoethane (3.9 g, 20.8 mmol) was added dropwise. The resultant dark brown mixture was heated at reflux for 3 h. The mixture was cooled to [0°C, ] and [N, N-DIMETHYLFORMAMIDE] (60 mL) was added in one portion. The mixture was partitioned with diethyl ether (3 x 400 mL) and 6N HCl (500 mL). The combined organic extracts were washed with brine (300 mL), dried [(NA2S04), ] filtered and concentrated in vacuo to give an oil. Flash chromatography (2x) on silica gel eluting with Hex: EtOAc (4: 1) afforded the sub- title compound (38.9 g, 54percent) as a yellow oil. [APOS;H] NMR (300 MHz, [CDC13)] [8] 9.90 (s, 1H), 7.53 (s, 1H), 7.38 (s, 1H), 7.15 (s, 1H), 3.87 (s, 3H).[5-DICHLOROANISOLE] (74.0 g, 419 mmol) in THF (200 mL) was added dropwise to magnesium metal (14.2 g, 585 mmol, pre-washed with 0.5 N HC1) in THF (100 mL) at [25°C.] After the addition, 1, 2-dibromoethane (3.9 g, 20.8 mmol) was added dropwise. The resultant dark brown mixture was heated at reflux for 3 h. The mixture was cooled to [0°C, ] and N, N-dimethylformamide (60 mL) was added in one portion. The mixture was partitioned with diethyl ether (3 x 400 mL) and 6N HCI (500 mL). The combined organic extracts were washed with brine (300 [ML), ] dried [(NA2SO4), ] filtered and concentrated in vacuo to give an oil. Flash chromatography (2x) on silica gel eluting with Hex: EtOAc (4: 1) afforded the sub- title compound (38.9 g, 54percent) as a yellow oil. 'H NMR (300 MHz, [CDC13)] 8 9.90 (s, 1H), 7.53 (s, 1H), 7.38 (s, 1H), 7.15 (s, 1H), 3.87 (s, 3H).3, [5-DICHLOROANISOLE] (74.0 g, 419 mmol) in THF (200 mL) was added dropwise to magnesium metal (14.2 g, 585 mmol, pre-washed with 0.5 N HCI) in THF (100 mL) at [25°C.] After the addition, 1, 2-dibromoethane (3.9 g, 20.8 mmol) was added dropwise. The resultant dark brown mixture was heated at reflux for 3 h. The mixture was cooled to [0°C, ] and N, N-dimethylformamide (60 mL) was added in one portion. The mixture was partitioned with diethyl ether (3 x 400 mL) and 6N HCI (500 mL). The combined organic extracts were washed with brine (300 mL), dried [(NA2SO4), ] filtered and concentrated in vacuo to give an oil. Flash chromatography (2x) on silica gel eluting with Hex: EtOAc (4: 1) afforded the sub-title compound (38.9 g, 54percent) as a yellow oil. 'H NMR (300 MHz, [CDCI3)] A 9.90 (s, 1H), 7.53 (s, 1H), 7.38 (s, 1H), 7.15 (s, 1H), 3.87 (s, 3H).[00325] A mixture of 3-chloro-5-methoxybenzyl alcohol (5.0g, 28.9 mmol) and pyridiniurn chlorochromate (20percent on alumina, 4Og, 37.8 mmol) was allowed to stir for 1.25 hr. Diethyl ether (200ml) was then added followed by filtration of precipitate. The filtrate was concentrated under reduced pressure and the resulting residue was purified via silica gel chromatography using 40percent dichloromethane, 60percent petroleum ether as eluant, to give 3.8g of 3-chloro-5-methoxybenzaldehyde (78percent). Preparation of 3-chloro-5-methoxybenzaldehyde 3, 5-Dichloroanisole [(74.] 0 g, 419 mmol) in THF (200 mL) was added dropwise to magnesium metal (14.2 g, 585 mmol, pre-washed with 0.5 N [HCL)] in THF (100 [ML)] at [25°C.] After the addition, 1, 2-dibromoethane (3.9 g, 20.8 mmol) was added dropwise. The resultant dark brown mixture was heated at reflux for 3 h. The mixture was cooled to [0°C, ] and [N, N-] dimethylformamide (60 mL) was added in one portion. The mixture was partitioned with diethyl ether (3 x 400 mL) and 6N HCl (500 mL). The combined organic extracts were washed with brine (300 mL), dried (Na2SO4), filtered and concentrated in vacuo to give an oil. Flash chromatography (2x) on silica gel eluting with Hex: EtOAc (4: 1) afforded the sub-title compound [(38.] 9 g, 54percent) as a yellow oil. [APOS;H] NMR (300 MHz, [CDCL3)] 8 9.90 (s, 1H), 7.53 (s, 1H), 7.38 (s, 1H), 7.15 (s, [1H), ] 3.87 (s, 3H).General procedure: 1H-Indole-3-carboxylate methylester 2 (1.0 mmol-equiv.) was refluxed with hydrazine hydrate(12.5 g, 0.25 M) in appropriate ethanol (30 mL) for 2 h. The progressof the reaction was monitored by TLC. After cooling the reactionmixture to room temperature, the mixtures were filtered to givewhite solid crude products without purification. Next, indolehydrazide(3, 1.0 mmol) in ethanol (30 mL) was added dropwiseinto the appropriate aldehyde (1.5 mmol-equiv.) and a few drops ofpropionic acid; the mixture was stirred and refluxed for 2.5 h. Aftercooling, the precipitates were filtered and washed several times bymethanol to yield the crystal substances 4aeu.

Molecular Weight:170.59
XLogP3:2.6
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:170.0134572
Monoisotopic Mass:170.0134572
Topological Polar Surface Area:26.3
Heavy Atom Count:11
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes