Synthesis
CuI (0.1 mmol, 19 mg), NaN3 (4 mmol, 260 mg), Cs2CO3 (2 mmol, 652 mg), and N-(2-bromophenyl)acetamide derivative (1 mmol) were added to a Schlenk tube equipped with a magnetic stir bar. The tube was evacuated and backfilled with nitrogen, repeated twice. Then, under a nitrogen stream, ethanol (5 mL) and N,N-dimethylethylenediamine (DMEDA) (0.2 mmol, 18 mg) were added sequentially at room temperature, and the tube was sealed. The reaction system was placed in a 95°C hot oil bath and stirred under a nitrogen atmosphere for 12–56 hours. After the reaction was completed, the resulting solution was cooled to room temperature, and the solvent was evaporated under vacuum. Then, 5 mL of hydrochloric acid (1N) was added to acidify the solution (pH 2–3). The reaction mixture was extracted with ethyl acetate (3 × 5 mL), and the combined organic phases were concentrated. The residue was purified by column chromatography on silica gel using petroleum ether/ethyl acetate (2:1) to obtain the target product, 2-amino-4-nitrobenzoic acid.
Chemical Properties
Orange crystalline powder
Physical properties
2-Amino-4-nitrobenzoic acid has three crystal structures
[1], respectively: monoclinic-1B, monoclinic-1C, and triclinic-1. Compound monoclinic-1B crystallises in the A ˚ space group P21/c with a = 4.039(4), b = 27.23(2), c = 7.284(7) Å, b = 112.783(15); compound monoclinic-1C crystallises in the space group P21/c with a = 3.71050(10), b = 25.3092(8), c = 24.3555 (17) A ˚ , b = 93.459(7) , and triclinic-1 crystallises in the space group P-1 with a = 3.7522(3), b = 8.5536(6), c = 24.4118(17), a = 88.738(9), b = 86.625(9), c = 87.769(9).
[1] SOLANGE M. S. V. WARDELL; James L W. Three New Polymorphs of 2-Amino-4-nitrobenzoic Acid[J]. Journal of Chemical Crystallography, 2015, 46 1: 34-43. DOI:
10.1007/s10870-015-0625-8.
Uses
2-Amino-4-nitrobenzoic acid (also known as 4-Nitroanthranilic acid) is primarily used as an intermediate in the synthesis of dyes and pharmaceuticals. It is also used in crystal or eutectic molecular structure research.
Definition
ChEBI: 4-nitroanthranilic acid is an aminobenzoic acid that is anthranilic acid with a nitro substituent at position 4. It has a role as a mutagen. It is an aminobenzoic acid and a nitrobenzoic acid. It is functionally related to an anthranilic acid.
General Description
Orange prisms or orange powder. Sweet taste.
Air & Water Reactions
Insoluble in water.
Reactivity Profile
4-Nitroanthranilic acid is incompatible with acids, acid chlorides, acid anhydrides, chloroformates and strong oxidizing agents.
Fire Hazard
Flash point data for 4-Nitroanthranilic acid are not available; however, 4-Nitroanthranilic acid is probably combustible.
reaction suitability
reaction type: solution phase peptide synthesis
Purification Methods
Crystallise the acid from water, EtOH (m 271o) or aqueous EtOH (m 269o). The acetyl derivative has m 217o (from EtOH), m 222o (from aqueous EtOH). [Chapman & Stephen J Chem Soc 1796 1925, Beilstein 14 II 234, 14 III 975, 14 IV 1087.]
