6-Chlorooxindole Chemical Properties

Melting point:

195-199 °C (lit.)

Boiling point:

329.0±42.0 °C(Predicted)

Density 

1.362±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

solubility 

soluble in Dimethylformamide

form 

powder to crystal

pka

13.39±0.20(Predicted)

color 

Light yellow to Brown

InChI

InChI=1S/C8H6ClNO/c9-6-2-1-5-3-8(11)10-7(5)4-6/h1-2,4H,3H2,(H,10,11)

InChIKey

CENVPIZOTHULGJ-UHFFFAOYSA-N

SMILES

N1C2=C(C=CC(Cl)=C2)CC1=O

CAS DataBase Reference

56341-37-8(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xn,Xi

Risk Statements 

22-43-36/37/38

Safety Statements 

37/39-36-26

WGK Germany 

3

Hazard Note 

Irritant

HS Code 

29337900

MSDS

• Language:English Provider:SigmaAldrich
• Language:English Provider:ALFA

6-Chlorooxindole Usage And Synthesis

Preparation

STEP A: 3-(2-nitro-4-chlorophenyl)pyruvic acid To a cooled mixture prepared by adding 13.6 g. of sodium to 300 ml. of ethanol is added a solution of 100 g. of 4-chloro-2-nitrotoluene and 84 g of diethyloxalate in 150 ml of ethanol while maintaining the temperature below 20℃. The resulting mixture is refluxed for one hour, cooled, 400 ml. of water added and the resulting mixture refluxed for 90 minutes. The ethanol is then evaporated to a small volume and the resulting precipi tate containstan and black material and the black mate rial is mechanically separated and discarded and the remainder (filtrate plus tan precipitate) used in the next step. STEP B: 4-chloro-2-nitro-phenylacetic acid The filtrate of Step A, above, is adjusted to pH 8-9 with 2 N sodium hydroxide and is heated at 35-40℃. while adding a 3-6% aqueous hydrogen peroxide solution until samples no longer turn dark on treatment with 2N sodium hydroxide. The tan precipitate is suspended in 1500 ml of water, adjusted to pH 8-9 and similarly treated with aqueous hydrogen peroxide. The combined reaction mixtures are then acidified with concentrated hydrochloride acid to obtain a precipitate which are re covered by filtration, washed 3 times with water and dried in vacuo. The crude product (mp 145-150° C) is recrystallized from ether to obtain 4-chloro-2-nitro phenylacetic acid, m.p. 156-159℃. STEP C: The product of Step B, above, is subjected to reductive cyclization analogously to Step B of Example 1 to obtain 6-chloro-oxindole, m.p. 185-189℃.

Description

6-Chlorooxindole is an organic compound that has been used in the pharmaceutical industry as a hydrogen bond donor and a dihydrate salt. It is an aromatic heterocycle with two rings, one of which is an oxindole ring. 6-Chlorooxindole has been shown to be stable at low pH and high temperatures, with the exception of hydrochloric acid. It is also soluble in water and can be prepared in a variety of ways, including by reacting benzene with nitrous acid or by heating oxindole with sodium hydroxide. 6-Chlorooxindole can be found as a component in some pharmaceutical preparations such as carbamazepine and ziprasidone. It can also be found as a component of the drug chlorpromazine.

Chemical Properties

Off-white to tan crystalline powder

Uses

6-Chlorooxindole is a useful research chemical used in the design of potent non-peptide MDM2 inhibitors.

Definition

ChEBI: 6-Chlorooxindole is a member of indoles.

Application

6-chlorooxyindole, also known as 6-chloro-2-indolone, is an intermediate of Ziprasidone hydrochloride. Ziprasidone is an atypical broad-spectrum antipsychotic developed by Pfizer for the treatment of schizophrenia with a strong affinity for serotonin and dopamine receptor antagonists, particularly the 5-HTA2/DAD2 receptor.

Synthesis

GENERAL PROCEDURE: TiCl4 (0.7 mL, 6 mmol) was added dropwise to a stirred suspension of Zn powder (0.78 g, 12 mmol) in freshly distilled anhydrous THF (15 mL) at room temperature and under a dry N2 atmosphere. After addition, the mixture was refluxed for 2 hours. After the formed suspension of low-valent titanium reagent was cooled, a solution of 6-chloroindole-2,3-dione (2 mmol) in THF (10 mL) was slowly added. The mixture was stirred at room temperature for about 5 min under N2 protection. Subsequently, the completion of the reaction was confirmed by thin layer chromatography (TLC) analysis. The reaction mixture was quenched with 3% HCl (15 mL) and extracted with CHCl3 (3 x 50 mL). The organic phases were combined, washed with water (3 x 50 mL) and dried over anhydrous Na2SO4. After concentration of the solvent under reduced pressure, the crude product was purified by column chromatography (petroleum ether/ethyl acetate = 5:1) to give 6-chlorooxindole.

References

[1] Tetrahedron Letters, 2014, vol. 55, # 14, p. 2238 - 2242
[2] Journal of Medicinal Chemistry, 1994, vol. 37, # 13, p. 2033 - 2042
[3] Patent: US4658037, 1987, A
[4] Patent: US4652658, 1987, A
[5] Patent: US4730004, 1988, A

6-Chlorooxindole(56341-37-8)Related Product Information

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