5- -6-chloro-oxindole

Piperazinyl-l,2-benzisothiazole hydrochloride 5-(2-Chloroethyl)-6-chloro-oxindole l-(l,2-Benzisothiazol-3-yl)piperazine... 

A clean and dry 20-gallon glass lined tank was charged with 19 L of water and 4.44 kg of sodium carbonate, after the carbonate had dissolved 4.29 kg (17.5 moles) of 5-(2-chloroethyl)-6-chloro-oxindole and 3.62 kg (16.5 moles) of 1-(l,2-benzisothiazol-3-yl)piperazine were added. The aqueous slurry was heated to reflux and the temperature maintained for 14 hours. When the reaction was complete the solution was cooled to 20°C and filtered. The wet product was reslurried in 23 L of isopropyl alcohol at room temperature for 2 hours. The product was collected by filtration on 2 large Buchner funnels, each was washed with 3.4 L of fresh isopropyl alcohol. The product was vacuum dried at 30° to 40°C. until no isopropyl alcohol remained, giving 5.89 kg (86.4% yield) of the desired free base which matched a standard sample by high performance liquid chromatography (HPLC). 

Nucleophilic processes that generate chloroindoles are largely confined to the displacements of oxy functions and Sandmeyer reactions of diazo-nium salts [81 H( 15)547]. A low yield of 2-chloroindole was obtained by a reaction sequence that involved treatment of oxindole with phosphoryl chloride, and then treatment of the Vilsmeier salt with sodium bicarbonate [66JOC2627 86H(24)2879]. It is, however, much better to prepare this compound from 2-lithioindole (92JOC2495). With phosphoryl chloride and dimethylformamide ethyl l-hydroxyindole-2-carboxylate failed to give the expected 3-formyl derivative. Instead there was a 50% yield of the 3-chloro derivative (84CPB3678). Diazonium salts have been used as precursors in... 

C,()H 4Cl3N 40371-11-7) see Levainisole P-chloro-)V-(2-chloroethyl)-Af-methylbenzeneethanamine (C11H15CI2N 22270-22-0) see Mianserin 6-chloro-5-(2-chloroethyl)oxindole... 

Although geneologically related to indoles, the dihydroindoles behave chemically rather like alkyl anilines. When diphenylamine reacts with chloro-propionyl chloride, amide 40 results this in turn readily cyclizes to oxindole 41. Sodium hydride followed by 2-chloroethyldimethylamine alkylates the 3-position (possibly through an intermediate aziridinium ion) partial demethylation is accomplished by refluxing with ethylchiorocarbonate, followed by hydrolysis of the intermediate carbamate to give indolinone 42, the antidepressant amedalin Repetition of this sequence on the chloropropyl homologue, followed by reduction of the appropriate indolinone produces dihydroindole 43, daledalin, which also has antidepressant activity. ... 

Anodic regioselective fluorination of a-phenylsulphenylated ethyl acetates, 1-naphthalene and 2-pyridine derivatives [80], l-aryl-3-(phenylthio)oxindoles and 2-substituted-3-oxo-4-(phenylthio)-l, 2, 3,4-tetrahydroisoquinolines [81], 2-benzo-thiazolyl and 5-chloro-2-benzothiazolyl sulfides [82], a-(phenylsulfenyl)lactams [83], as well as various heterocycles such as thiolanones, oxathiolanones, dithi-olanones, 3Fl-l,4-benzoxathian-2-ones [84] in Et3N-3HF or Etr NF- HF [n = 3,4), has been reported. 

When the substrate has no alkyl groups on N, the dianion formed by LDA in THF also reacts under irradiation to afford oxindoles in good yields. Photocyclization of 2-chloro-3-(A-methylacetamido)pyridine by means of KNH2 in liquid ammonia or LDA in THF gave azaoxindoles in good yields (62 and 83%, respectively)338. 

Cabucine (10-methoxyajmalicine) (135) and tetraphylline (11-methoxyaj-malicine) (136) have been converted into the corresponding oxindole A and B analogues (137-140) via the corresponding 7-chloro-indolenine derivatives.82... 

The reaction of yohimbine hydrochloride with m-chloroperbenzoic acid also results in the formation of a 7-chloro-indolenine derivative hence the product, following normal Ab-oxidation, is the JVb-oxide (141). In contrast to the 7-chloro-indolenine derivatives, no conversion into the corresponding oxindole analogue... 

Cyclization of the anilide 213 using TiCU produced the 3-chloro-substituted oxindole 214 (Equation 69), whereas a similar reaction induced by BF3-OEt2 gave the corresponding methoxy-substituted derivative <1998T4889>. Lewis acids have also been used in an approach to indole-2-carboxylates based on cyclization of (Z)-A(A -dimethyl-aminopropenoates derived by exposure of A -arylglycinates to DMEDMA <2006SL749>. 

The interaction of oxindole with the Vilsmeier reagent produces 2-chloro-3-formylindole efficiently this difunctional indole has considerable potential for elaboration, for example nucleophilic displacement of the halogen, activated by the orf/to-aldehyde, can produce indoles carrying a nitrogen substituent at C-2. ... 

Grant and Krische have described a racemic protocol for the synthesis of allcarbon C3 quaternary centers from 3-hydroxy-3-tert-prenyloxindole 76 that was accessed via ruthenium catalyzed addition of 1,1-dimethylallene 75 to isatin 74 [45]. As outlined in Scheme 21, 76 was converted to the electrophilic 3-chloro derivative, which was trapped with indole under basic conditions to afford 78 in 60% yield. A mechanism has been proposed for the C-C bond-forming event that involved first-order irmizatirHi of chloride irm assisted by delocaUzatiOTi of oxindole... 

Lysine salt of 6- Chloro - 5- fluoro-3 (2-thienyl)-2 oxindole -1- carboxamide... 

The authors have found that nitronates 11 are derived from intramolecular nucleophilic displacement of the chloro atom with oxygen of the nitro group (Scheme 9). Moreover, the intramolecular VNS reactions of nitroarenes proved to be a successful procedure for the synthesis of various indole derivatives. For instance, cyclization of 3-nitrochloroacetanilide 12 caused by action of f-BuOK affords N-substituted oxindole 13, which is hardly accessible by other methods [28] (Scheme 10). 

The interaction of oxindole with the Vilsmeier reagent produces 2-chloro-3-formylindole efficiently this difunctional indole has considerable potential... 

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