Synthesis and Application of 3,5-Dinitrobenzoic Acid

3,5-Dinitrobenzoic acid serves as a crucial organic synthetic intermediate. In the pharmaceutical industry, it is utilized for synthesizing compounds such as Diatrizoic acid. Within the dye industry, it functions as a building block for the production of the dye intermediate 3,5-diaminobenzoic acid. Furthermore, in the liquid crystal industry, it is employed in synthesizing liquid crystal intermediates, exemplified by 3,5-diaminobenzoic acid 4-biphenylyl ester. This compound represents an emerging high-value-added fine chemical product with significant industrial relevance.

The Application of 3,5-Dinitrobenzoic Acid

1. Application of 3,5-dinitrobenzoic acid in liquid crystal materials

Polyimides (PIs) are a class of organic polymer materials characterized by imide rings (-CO-N-CO-) in their molecular backbones, which can be classified into cross-linked and non-cross-linked types based on their network structures. Owing to their exceptional comprehensive properties, including excellent dimensional stability and inherent backbone thermal resistance, PIs are widely utilized in the fabrication of structural materials such as liquid crystal composites and advanced functional materials.

Starting from 3,5-dinitrobenzoic acid as the precursor, the target diamino compound bearing liquid crystalline side groups, namely 4'-biphenyl 3,5-diaminobenzoate, was synthesized via a sequence of reactions including nucleophilic substitution and catalytic hydrogenation. Utilizing this diamine derivative as a comonomer, a side-chain liquid crystalline polyimide (LC-PI) film material was fabricated. This material exhibits pronounced self-reinforcement and in-situ composite functionalities, accompanied by excellent mechanical properties and thermal stability.^[1-2]

2. Applications of 3,5-Dinitrobenzoic Acid in the Medical Field

Borneol is a traditional medicinal compound with antipyretic and anti-inflammatory properties, exhibits limitations in clinical application due to its low boiling point (95-98℃ at 15 mmHg) and inherent volatility, coupled with reported toxic side effects including neurotoxicity and mucosal irritation. To address these issues, prodrug modification was performed via esterification of the hydroxyl group in the borneol scaffold using carboxylic acid moieties. As illustrated in Figure 1, the ester derivative was synthesized through nucleophilic acyl substitution between borneol and 3,5-dinitrobenzoic acid, yielding borneol 3,5-dinitrobenzoate—a structural modification consistent with reported terpenoid esterification strategies.^[3-4]

Fig.1 Synthetic route of borneol ester derivatives

Creatinine is a toxic component that can accumulate latently in human blood. If not promptly cleared, it can readily cause chronic renal failure in patients. In the human body, creatinine can form a specific and stable complex with starch 3,5-dinitrobenzoate, which can be excreted through the urinary system.^[5]

Diatrizoic acid, chemically named 3,5-diacetamido-2,4,6-triiodobenzoic acid dihydrate, serves as a primary active pharmaceutical ingredient in positive contrast agents for X-ray diagnostics. It is widely utilized in the formulation of water-soluble contrast media injections, including meglumine diatrizoate and compound meglumine diatrizoate preparations. The synthetic pathway to diatrizoic acid involves a three-step transformation starting from 3,5-dinitrobenzoic acid, as illustrated in Figure 2:^[6]

Fig.2 Synthetic route of diatrizoic Acid

3. Applications of 3,5-Dinitrobenzoic Acid in the Other Field

Energetic complexes have become a topic of high interest in the field of energetic materials for their applications as primary explosives, pyrotechnics, and combustion catalysts. Recently, nitrogen-rich ligands with plentiful lone-pair electrons were selected to design and develop novel energetic complexes, due to their high energy derived from the transformation of N-N (160 kJ mol⁻¹) and N=N (418 kJ mol⁻¹) bonds and eco-friendly decomposition products. 3,5-Dinitrobenzoic acid (HDNBA) is a 3,5-dinitro substituted benzoic acid derivative, which has aroused significant interest in organic supramolecular architecture and metallorganics for catalyst, optical and magnetic materials applications.^[7]

 Fig.3 Molecular structure and labeling of energetic complexes

Method of Synthesis of 3,5-Dinitrobenzoic Acid

Currently, there are two main methods for synthesizing 3,5-dinitrobenzoic acid:

1. Using 1,3-dinitrobenzene as the raw material, 3,5-dinitrobenzoic acid is prepared via a carbonylation insertion reaction. The specific operations are as follows:^[8]

Triphenylphosphine ditriflate (0.672 g, 1.2 mmol) was dissolved in ethanol (3 mL), and sodium hydrogen carbonate (0.084 g, 1 mmol) was subsequently added to the solution. The resulting mixture was stirred at room temperature for 30 minutes, followed by the addition of arene (0.14 mL, 1 mmol). Stirring was continued at room temperature for an additional 120 minutes, with reaction progress monitored by thin-layer chromatography (TLC).Upon completion, the solvent was removed under reduced pressure. The residue was treated with saturated sodium bicarbonate solution (10 mL) and extracted with chloroform (3×5 mL). The combined organic layers were washed with water and dried over anhydrous magnesium sulfate. After filtration, the filtrate was evaporated to dryness. The crude product was purified by silica gel column chromatography using ethyl acetate/n-hexane (3:7, v/v) as the eluent, yielding 3,5-dinitrobenzoic acid as the final product.

2. Using benzoic acid as the raw material, 3,5-dinitrobenzoic acid is synthesized through nitration with a mixed acid composed of fuming nitric acid and concentrated sulfuric acid. The specific operations are as follows:^[6]

A suitable reaction vessel was charged with 1151 gm (11.74 mol) of sulfuric acid and 250 gm of benzoic acid (2.049 mol) and mixed well for 1 hr at 25-30°C. Then the reaction mass was allowed to cool to 5-10°C, at this temperature, added 189 gm (3.00 mol) of fuming nitric acid slowly over about 90-120 min. During the addition, the temperature observed to be increased to 40-45°C and held constant. Then slowly raised the temperature to 60-65°C and maintained at this temperature for 3 hrs. After that, the reaction mass temperature maintained at 80°C-85°C by gentle heating and stirred for 24h. After completion of the reaction by HPLC, (SM<1%) the reaction mass was allowed to RT and charged in to ice cold water and stirred for 60 minutes at 5-10°C. The solid resulted was isolated by filtration and washed with chilled water and dried.

References

[1] Li, Xiaohong; Mushtaq, Nafeesa. Synthesis and characterization of low retardation colorless polyimides containing m-phenylenediamine with different pendant groups. [J]High Performance Polymers (2024), 36(6-7), 357-366.

[2] Hajipour, Abdolreza. Polyimides: Synthesis properties, characterization and applications. Handbook of Engineering and Specialty Thermoplastics (2012), 4, 211-288.

[3] Chen,Chuan-bing. Synthesis and structure identification of borneol 3,5-dinitro benzoate.[J]Guangzhou Huaxue (2012), 37(4), 23-25.

[4] Korvola, Jorma. Thermal decomposition of p-nitrobenzoates and 3,5-dinitrobenzoates of borneol and isoborneol.[J] Finnish Chemical Letters (1974), (1), 23-4.

[5] Jiugao Yu, Synthesis and Application of Starch 3,5-Dinitrobenzoate, [J]Starch/St?rke 55 (2003) 17-24.

[6] Assignee, A new process for preparation of high pure diatrizoic acid and its intermediates from benzoic acid by nitration, reduction, iodination and N-acetylation.[P]IN201614017272.

[7] Li, Zhimin. Nitrogen-Rich Ligands Directed Transition Metal (Co/Ni/Zn) 3,5-Dinitrobenzoic Acid Energetic Complexes: Syntheses, Crystal Structures and Properties.[J] ChemistrySelect (2018), 3(37), 10298-10304.

[8] Khodaei, Mohammad M., Direct carboxylation of aromatic compounds using the sodium hydrogen carbonate/triphenylphosphine ditriflate system, Comptes Rendus Chimie (2018), 21(1), 27-31.

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