Lin Zhanga,
Qinglang Songa,
Yanxian Wanga,
Rui Chena,
Yu Xiaa,
Bin Wang
a,
Weiwei Jin
a,
Shaofeng Wua,
Ziren Chena,
Azhar Iqbal*b,
Chenjiang Liu
*a and
Yonghong Zhang
*a
aState Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, Key Laboratory of Oil and Gas Fine Chemicals, Ministry of Education & Xinjiang Uygur Autonomous Region, Urumqi Key Laboratory of Green Catalysis and Synthesis Technology, College of Chemistry, Xinjiang University, Urumqi 830017, P. R. China. E-mail: zhzhzyh@126.com; pxylcj@126.com
bDepartment of Chemistry, Bacha Khan University, Charsadda, Pakistan. E-mail: azhariqbal@bkuc.edu.pk
First published on 9th August 2024
An efficient diazotization of phenolic compounds with aryltriazenes is herein demonstrated by employing ball milling under catalyst-, promoter- and solvent-free conditions. The present protocol offers several advantages including mild conditions, good selectivity and high yields, simple operation and practical gram-scale synthesis. Overall, this novel strategy significantly improves the reaction efficiency, simplifies purification procedures of the diazotization reaction and provides potential for the industrial preparation of azo dyes.
Azo dyes are organic compounds that contain –NN– groups,12 which were the most common dyes (more than 3000 different varieties) used in the textile industry compared to natural dyes due to their low cost, versatility and colouring ability.13 They account for approximately 70% of the total amount of dyes, and besides the textile industry, azo dyes are also intensively used in the cosmetics, leather, paper, food and pharmaceutical industries.14 Consequently, various methods were developed for synthesis of azo dyes. Typically, most of these compounds were prepared from aromatic primary amine via the diazotization reaction with nitrite to produce aryl diazonium salts, followed by coupling with nucleophiles.14–19 In particular, environmentally friendly protocols for the synthesis of azo dyes via the diazotization and coupling of diazonium salts with phenols or aromatic amines have attracted much attention in recent years, such as: (a) the coupling reaction of resin supported diazonium salts with nucleophiles;20 (b) gas–solid diazotization of 3-aminopyrazolo[3,4-b]pyridine/solid–solid cascade coupling with nucleophiles;21 (c) in situ diazotization of p-nitroaniline with sodium nitrite and coupled with N,N-diethylaniline in supercritical carbon dioxide under mineral acid-free conditions;22 (d) one pot diazo coupling under microwave irradiation;23 (e) the sonochemical method of diazotization and coupling;24 (f) continuous flow diazotization and coupling in a microreactor system,25 etc. However, all of the above methods have one or more disadvantages, such as the use of solvents in the reaction. The solvent becomes liquid waste after the reaction, resulting in environmental pollution. In addition, some products formed are poorly soluble in the solvent, thus making the reaction and post-treatment process even more complicated. Nowadays, green chemistry and sustainable approaches for organic synthesis have gained tremendous importance due to environmental and ecosystem based concerns. Mechanochemistry assisted organic reactions are proven to be energy efficient, green,26 fast, solvent-free, and reproducible, show good selectivity, and lead to higher yields.27,28 Although diazonium salts are common reagents for the synthesis of azo dyes, however, their potentially explosive hazards and unstable nature highly restricted their application, especially for the large scale synthesis of azo dyes. Therefore, developing stable and mild alternative reagents to replace aryl diazonium salts is highly desirable. Recently, as the masked surrogates of corresponding diazonium salts, aryltriazenes have been widely applied in a variety of synthetic transformations due to their good stability, multiple reactive sites, and mild reaction conditions.29–31 In particular, they were also used for the efficient synthesis of azo dyes via diazotization of phenolic compounds. In 2018, our group developed an ionic liquid promoted diazotization of naphthols with aryltriazenes for the synthesis of azo dyes.19 In 2021, Jewett's group reported a UV light induced diazotization of phenol with aryltriazenes for protein modification.32 Herein, we developed a novel metal-, promoter-, catalyst- and solvent-free method for the synthesis of various azo dyes in excellent yields and regioselectivity using ball milling with aryltriazenes as diazotization reagents (Scheme 1).
Entry | Variation from the “standard conditions” | Yieldb (%) |
---|---|---|
a Reactions condition: 1a (1.0 mmol), 2a (1.2 mmol), and 5 mm stainless steel balls were added to a 50 mL stainless steel tank, 300 r for 3 h.b Isolated yield.c 1a (1.0 mmol), 2a (1.2 mmol) and MeCN (1 mL) stirred in a 10 mL glass tube for 3 h at room temperature. | ||
1 | None | 92 |
2 | 100 μL MeCN as an auxiliary grinding agent | 90 |
3 | 100 μL MeOH as an auxiliary grinding agent | 89 |
4 | 100 μL H2O as an auxiliary grinding agent | 91 |
5 | 1.1 mmol 2a | 89 |
6 | 5 mm (6 balls) instead of 5 mm (20 balls) | 40 |
7 | 5 mm (12 balls) instead of 5 mm (20 balls) | 77 |
8 | 8 mm (1 balls) instead of 5 mm (20 balls) | 47 |
9 | 8 mm (3 balls) instead of 5 mm (20 balls) | 90 |
10 | 8 mm (6 balls) instead of 5 mm (20 balls) | 68 |
11 | 8 mm (10 balls) instead of 5 mm (20 balls) | 63 |
12 | 2 hours instead of 3 hours | 47 |
13 | 4 hours instead of 3 hours | 93 |
14 | 200 rpm instead of 300 rpm | Trace |
15 | 400 rpm instead of 300 rpm | Trace |
16 | Zirconia balls instead of stainless steel balls | 90 |
17 | Mixing without rotational speed | n.r. |
18c | Solution reaction | Trace |
Once the reaction conditions were optimized, we performed substrate generalization studies by using β-naphthol, α-naphthol and resorcinol derivatives with aryltriazenes, respectively. First, the substrate range of β-naphthol with aryltriazenes was examined (Table 2, 3a–3i). The reaction was generally effective for electron-donating substituents, most of which can afford moderate to good yields. Both para- and meta-methyl substituted aryltriazenes are compatible with the reaction, and the desired products can be obtained in 92% and 80% yields (3a and 3b), respectively. However, the ortho-substituted substrate reacted less effectively, with a yield of only 38% (3c), which is possibly due to the steric hindrance effect. To our delight, non-substituted phenyltriazene (2d), 4-iPr (2e) and 4-tBu (2f) substituted aryltriazenes delivered good to excellent yields. Furthermore, excellent yields of up to 98% and 91% were obtained when 4-OMe and 4-OEt substituted aryltriazenes were subjected to the reaction (3g and 3h). Notably, the polycyclic aryltriazene also showed good compatibility, and the target product 3i can be obtained in 79% yield. Then, we examine the universality of substituted β-naphthols, such as 3-methoxy-2-naphthol (1j) and 6-methoxy-2-naphthol (1k), which smoothly reacted and obtained the corresponding products in 85% and 87% yields, respectively. Fortunately, 2-naphthols bearing electron-withdrawing substituents (bromo & cyano) were also tolerated, and target products 3l and 3m can be afforded in good yield. Finally, the reactivity of α-naphthol towards substituted aryltriazenes was investigated, such as p-Me (2n), m-Me (2o) and o-Me (2p) substituted phenyltriazenes, which were also tolerated, and the corresponding products 3n–3p were generated in 41% to 84% yield.
The substrate scope of various aryltriazenes with resorcinol under the established optimal conditions was next evaluated (Table 3). The results showed that various aryltriazenes bearing electron-donating groups (4-Me, 4-iPr, 4-tBu, 4-OMe and 4-OEt) on the benzene ring and non-substituted substrates all reacted smoothly with resorcinol 4a. Besides sterically hindered ortho-methyl substituted triazene (5c) that afforded 35% yield, the desired products 5a–5h were obtained in moderate to good yields (60–98%). In addition, substituted resorcinol compounds such as (E)-4-pentyl-6-(p-tolyldiazenyl)benzene-1,3-diol (4i) also achieved moderate yields. Notably, due to the poor solubility of resorcinol products in low polar solvents such as petroleum ether or hexane, they can be easily isolated and purified by simple filtering and washing with hexane after the reaction.
To demonstrate the practical utility of this mechanochemical synthesis method, the reaction of resorcinol 4a and p-methylphenyltriazene 2a was performed at the 20 mmol scale (Scheme 2). The results showed that this protocol could be successfully performed on a gram scale, and the desired product 5a was obtained smoothly in 91% yield at room temperature in 6 hours of ball milling under solvent-free conditions. It is worth mentioning that the target product (E)-4-(p-tolyldiazen-yl)benzene-1,3-diol (5a) was almost insoluble in petroleum ether (PE) and ethyl acetate (EA), while the unreacted resorcinol 4a and p-methylphenyltriazene 2a are soluble in the above organic solvents. Therefore, as shown in Fig. 1, after the completion of the reaction, the product can be easily isolated from the reaction mixture via washing with petroleum ether (PE) (3 × 15 mL) and water (3 × 15 mL), respectively.
To gain insight into the reaction mechanism, a control experiment was carried out (Scheme 3). Under standard conditions, 2-methoxynaphthalene 6a was used to replace β-naphthol 1a to react with p-methylphenyltriazene 2a. As expected, no corresponding product 7a was obtained, suggesting that the weak acidity of the hydroxyl group of β-naphthol 1a plays a role in activating the aryltriazene to provide an aryldiazonium cation for further diazotization.
Based on literature reports23,29 and mechanism validation experiments, a plausible reaction mechanism is presented in Scheme 4. First, aryltriazene 2a undergoes N2–N3 cleavage via hydrogen bond activation in the presence of weak acid β-naphthol to form an electron donor–acceptor (EDA) complex of aryl diazonium cation and naphthalen-2-olate. Subsequently, the dearomatized intermediate B was obtained through electrophilic addition of the aryldiazonium cation to naphthalen-2-olate. Finally, product 3a was produced through 1,3-proton transfer and restores aromaticity.
Footnote |
† Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d4mr00053f |
This journal is © The Royal Society of Chemistry 2024 |