5-Nitroindole-2-carboxylic acid

5-Nitroindole-2-carboxylic acid Property

Melting point:

>300°C

Boiling point:

520.8±30.0 °C(Predicted)

Density 

1.632±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

form 

Solid

pka

4.09±0.30(Predicted)

Appearance

Light yellow to brown Solid

CAS DataBase Reference

16730-20-4(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

HazardClass 

IRRITANT

HS Code 

2933998090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P405Store locked up.

5-Nitroindole-2-carboxylic acid Chemical Properties,Usage,Production

Uses

5-Nitroindole-2-carboxylic acid is an important pharmaceutical intermediate, especially as an intermediate in the preparation of drugs for treating AIDS.

Synthesis

General procedure for the synthesis of 5-nitroindole-2-carboxylic acid from ethyl 5-nitroindole-2-carboxylate: lithium hydroxide monohydrate (LiOH-H2O, 1.06 g, 46.2 mmol, 2.1 eq.) was added to ethyl 5-nitro-1H-indole-2-carboxylate (II, 5.15 g, 22 mmol, 1 eq.) in a suspension of a mixed solvent (180 mL) in a 1:1:2 ratio of tetrahydrofuran (THF), methanol (MeOH) and water (H2O) in a solvent mixture (180 mL) with a ratio of 1:1:2. The reaction mixture rapidly changed to a dark yellow color and was stirred continuously at 25 °C. After 30 min, the reactants were completely dissolved and the reaction was fully converted after 6 h. The reaction mixture was cooled to 0 °C and the reaction mixture was then converted to a dark yellow color with constant stirring. The reaction mixture was cooled to 0 °C and the pH was adjusted to 5 with 2N hydrochloric acid (HCl) to terminate the reaction. Subsequently, the organic volatiles were removed by evaporation under reduced pressure and filtered to give a white precipitate, which was dried to give the target product 5-nitroindole-2-carboxylic acid (III). The yield was 4.53 g (quantitative yield) in small scale experiments. In a 50 g scale reaction, the same procedure was followed to give 42.2 g of compound III in 96% yield. The product was analyzed by liquid chromatography-mass spectrometry (LCMS, HPLC method 2) and showed m/z 205 [MH]- (retention time 2.58 min). Nuclear magnetic resonance hydrogen spectroscopy (1H NMR, 400 MHz, DMSO-d6) data were as follows: δ 2.59 (dd, J = 15.91, 5.67 Hz, 1H), 2.82 (dd, J = 15.97, 8.29 Hz, 1H), 3.58 (dd, J = 12.86, 5.67 Hz, 1H), 3.89 (dd, J = 13.35 , 4.08 Hz, 1H), 5.17-5.23 (m, 1H), 7.36 (s, 1H), 7.80 (d, J = 9.15 Hz, 1H), 8.15 (dd, J = 9.15, 2.32 Hz, 1H), 8.27 (d, J = 5.12 Hz, 1H), 8.72 (d, J = 2.32 Hz, 1H), 12.58 (br.s., 1H).

References

[1] Patent: WO2009/118411, 2009, A2. Location in patent: Page/Page column 37
[2] Patent: WO2004/56768, 2004, A2. Location in patent: Page 31; 78
[3] Patent: WO2006/10008, 2006, A1. Location in patent: Page/Page column 221
[4] Patent: WO2006/40180, 2006, A1. Location in patent: Page/Page column 99
[5] Patent: US9226970, 2016, B2. Location in patent: Page/Page column 40