4-CHLORO-1,3-DIHYDRO-INDOL-2-ONE

General procedure: TiCl4 (0.7 mL, 6 mmol)was added to a stirred suspension of Zn powder (0.78 g, 12 mmol) in freshlydistilled anhydrous THF (15 mL) at room temperature (rt) under a dry N2atmosphere. After completion of the addition, the mixture was refluxed for 2 h.The suspension of the low-valent titanium reagent thus-formed was cooled tort. A solution of isatin or its derivatives 1 or 3 (2 mmol) in THF (10 mL) wasadded dropwise. The mixture was stirred at room temperature for about 5 minunder N2. After this period, the thin layer chromatography (TLC) analysis of themixture showed the reaction completed. The reaction mixture was quenchedwith 3percent HCl (15 mL) and extracted with CHCl3 (3 50 mL). The combinedextracts were washed with water (3 50 mL) and dried over anhydrousNa2SO4. After evaporation of the solvent under reduced pressure, the crudeproduct was purified by column chromatography (petroleum ether/ethylacetate = 5:1) to give the pure products 2 or 4.5-n-Butyl-2-oxindole can be prepared by reaction of 5-n-butylisatin with hydrazine hydrate followed by sodium methoxide in ethanol, according to the procedure of Preparation 1. 5-n-Butylisatin can be prepared from 4-n-butylaniline by treatment with chloral hydrate and hydroxylamine, followed by cyclization with sulfuric acid, according to the procedure of Parts A and B of Preparation 3.5-Cyclopropyl-2-oxindole and 5-cycloheptyl-2-oxindole can be prepared by reaction of 5-cyclopropylisatin and 5-cycloheptylisatin, respectively, with hydrazine hydrate followed by sodium methoxide in ethanol, according to the procedure of Preparation 1. 5-Cyclopropylisatin and 5-cycloheptylisatin can be prepared from 4-cyclopropylaniline and 4-cycloheptylaniline, respectively, by treatment with chloral hydrate and hydroxylamine, followed by cyclization with sulfuric acid, according to Parts A and B of Preparation 3.General procedure: Weigh isatin (0.8g, 5.4mmol), the first of which was added 0.3g of 80% hydrazine hydrate (10ml) and heated to 100 C under reflux, was added portionwise remaining 0.5g, 2h addition was completed the temperature was raised to 110 C reflux was continued for 4h, cooled to room temperature, concentrated hydrochloric acid was added dropwise 36% was adjusted to pH = 3, stirring was continued at room temperature for 12h, the solid by suction filtration, washed with water and precipitation to give a brown solid (0.44g, 61%).(G) General procedure: The appropriate compound 2 (10 mmol) was dissolved inmethanol (100 mL) and treated with the equivalent of the appropriatealdehyde 1 and piperidine (1 mL). For compounds 39, 41 and42 the yield was much lower (5%), and an improvement (15-20%)was obtained by replacing piperidine with 33% NH4OHThe reaction mixture was refluxed for 5-10 h, except for compounds39-42 which required a longer reflux time (16-24 h; theprogress of the reaction was followed by TLC). The precipitate, formed on cooling, was collected by filtration.Compounds 39e41 were purified by column chromatographywith petroleum ether/acetone as the eluent. Most of the crudeproducts were crystallized from methanol, except 27 (acetone/petroleumether), 34, 43-48, 50-52 (ethanol) and 42, 49 (toluene). Inthe case of compound 10, the two E/Z isomers were isolated byfractional crystallization from methanol.

Molecular Weight:167.59
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:167.0137915
Monoisotopic Mass:167.0137915
Topological Polar Surface Area:29.1
Heavy Atom Count:11
Complexity:183
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes