Lingjun Li,
Anlian Zhu*,
Yuqin Zhang,
Xincui Fan and
Guisheng Zhang
School of Chemistry and Chemical Engineering, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang, Henan 453007, P. R. China. E-mail: anlian_cn@aliyun.com
First published on 8th November 2013
Fe2(SO4)3·xH2O on silica has been found to be a novel efficient catalyst for the direct nucleophilic substitution of alcohols in solvent-free conditions. In this reaction system, the alcohols can react with various nucleophilic reagents for the convenient construction of C–C bonds and C–N bonds with the benefits of high conversion, no requirement to use excessive amounts of the nucleophile, only a catalytic amount of iron catalyst required, solvent-free and benign reaction conditions, and the feasible reusability of the catalyst.
Benefiting from its low cost, relatively non-toxic nature, distinct Lewis acid character and feasible accessibility, iron is believed to be a rising star in metal catalysis.13,14 Here, the commercial iron salt Fe2(SO4)3·xH2O supported on silica gel was found to be an efficient heterogeneous catalyst for direct nucleophilic substitution reactions of alcohols under mild conditions. This catalytic system has a wide substrate tolerance with high conversion and selectivity, even in the water environment of the iron salt and hydroxyl groups on silica, and benefits from no requirement to use excessive amounts of the nucleophile, an easy work-up and the feasible reusability of the catalyst. The possible mechanism for the excellent performance of this catalytic system has also been proposed in this work.
The performances of different catalytic systems based on Fe2(SO4)3·xH2O was studied using the reaction between benzoylacetone 1a and benzhydryl alcohol 2a as a model and the results are collected in Table 1. It was found that when this reaction was conducted in traditional solvents such as CH2Cl2 and CH3NO2 at room temperature or under reflux conditions, the reaction was sluggish and the target compounds were poorly obtained even after 5 hours. When the reaction was conducted in water at room temperature, the reaction did not proceed, but under reflux conditions, the target compound was produced in 10% yield after 5 hours, suggesting that water is not strictly forbidden in this reaction when catalysed with Fe2(SO4)3·xH2O. It is well known that silica gel has a high adsorptive ability and the hydroxyl groups together with adsorbed water on its surface can form local hydrophilic centers. This has found interesting applications in organic synthesis recently.15,16 Interestingly, in this work, we found that when the iron salt Fe2(SO4)3·xH2O was supported on silica, which has no obvious catalytic activity by itself (entry 11, Table 1), the yield of the target compound was significantly increased. Additionally, when the reaction was conducted at a temperature of 75 °C, the target compound was almost quantitatively isolated within 0.5 hours (entry 10, Table 1).
Entrya | Solvent or medium | Temperature (°C) | Time (h) | Isolated yield (%) |
---|---|---|---|---|
a 1a (0.25 mmol), 2a (0.25 mmol) and Fe2(SO4)3·xH2O (12.5 mg, 0.025 mmol) in 5 mL of solvent were stirred at a certain temperature.b 200 mg silica gel was used as the reaction medium.c In the absence of Fe2(SO4)3·xH2O. | ||||
1 | CH2Cl2 | 25 | 5 | 0 |
2 | CH2Cl2 | Reflux | 5 | 0 |
3 | CH3NO2 | 25 | 5 | 30 |
4 | CH3NO2 | Reflux | 5 | 55 |
5 | H2O | 25 | 5 | 0 |
6 | H2O | Reflux | 5 | 10 |
7 | Silicab | r.t. | 5 | 10 |
8 | Silicab | 35 | 0.5 | 41 |
9 | Silicab | 55 | 0.5 | 89 |
10 | Silicab | 75 | 0.5 | 98 |
11c | Silicab | 75 | 0.5 | Trace |
The high catalytic activity of Fe2(SO4)3·xH2O supported on silica for the model reaction encouraged us to investigated the substrate scope of this method for the direct nucleophilic substitution of alcohols. The successful results are collected in Table 2. It was found that, besides benzoylacetone 1a, 1,3-dicarbonyl compounds such as acetylacetone 1b and ethyl acetoacetate 1c could also react with benzhydryl alcohol 2a smoothly and gave excellent isolated yields within 0.5 hours (Table 2, entry 1–3). N-Nucleophiles such as nitroaniline 1d, sulfonamide 1e, amide 1f, and 2,4-DNPH 1g also reacted smoothly with a stoichiometric amount of the alcohol to give the N-alkylation products with good to excellent yields in 0.5–1 hour (Table 2, entry 4–7). The scope of this reaction with respect to the alcohol substrates was also examined (Table 2, entry 8–15). It was shown that the benzhydryl alcohol with chlorine substituents 2b could react with the dicarbonyl compound 1a and nitroaniline 1d smoothly to give almost quantitative isolated yields (Table 2, entries 8 and 9). The benzhydryl alcohol with strong withdrawing substituents 2c could react with nitroaniline 1d at room temperature to give a quantitative isolated yield in 1 hour (Table 2, entry 10). Benzylic alcohols 2d–2f could react with sulfonamide 1e smoothly to give excellent yields under mild conditions (Table 2, entries 11–13). Allyl alcohol 2g was also found to be a suitable substrate for this direct nucleophilic substitution reaction using this catalytic system, and gave the desired product in 93% yield within 0.5 hours (Table 2, entry 14). Moreover, primary alcohol 2h could react effectively with 1a to give product 3o in 92% yield (Table 2, entry 15).
Entrya | Nucleophiles | Alcohol | Products | Temperature (°C) | Time (h) | Isolated Yield (%) |
---|---|---|---|---|---|---|
a Reaction conditions: 1 (0.25 mmol), 2 (0.25 mmol), Fe2(SO4)3·xH2O (12.5 mg, 0.025 mmol), and silica gel (200 mg) were stirred under certain temperature. | ||||||
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1 | ![]() |
2a | ![]() |
75 | 0.5 | 98 |
2 | ![]() |
2a | ![]() |
75 | 0.5 | 89 |
3 | ![]() |
2a | ![]() |
75 | 0.5 | 90 |
4 | ![]() |
2a | ![]() |
75 | 0.5 | 95 |
5 | ![]() |
2a | ![]() |
75 | 0.5 | 92 |
6 | ![]() |
2a | ![]() |
75 | 1 | 85 |
7 | ![]() |
2a | ![]() |
75 | 0.5 | 81 |
8 | ![]() |
2b | ![]() |
75 | 0.5 | 97 |
9 | ![]() |
2b | ![]() |
75 | 0.5 | 96 |
10 | ![]() |
2c | ![]() |
r.t. | 1 | 95 |
11 | ![]() |
2d | ![]() |
75 | 0.5 | 90 |
12 | ![]() |
2e | ![]() |
75 | 0.5 | 89 |
13 | ![]() |
2f | ![]() |
r.t. | 1 | 91 |
14 | ![]() |
2g | ![]() |
75 | 0.5 | 93 |
15 | ![]() |
2h | ![]() |
75 | 1 | 92 |
Additional experiments were designed to illustrate the role of Fe2(SO4)3·xH2O–silica on the promotion of the reaction procedure. Bis(4-methoxyphenyl)methanol 2c was selected as a model, which could produce a red bis(4-methoxyphenyl)methyl cation 4[+] (Fig. 1). By comparing photographs (a), (b) and (c) in Fig. 1, it can be concluded that Fe2(SO4)3·xH2O–silica promotes bis(4-methoxyphenyl)methanol to efficiently produce the bis(4-methoxyphenyl)methyl cation. The resulting mixture of Fe2(SO4)3·xH2O–silica and the bis(4-methoxyphenyl)methyl cation could keep the red colour for over 1 hour in an air atmosphere, which implied that Fe2(SO4)3·xH2O–silica can stabilize the active bis(4-methoxyphenyl)methyl cation. However, when a drop of ethyl acetate was added into this mixture, the red colour disappeared immediately, which indicated that organic solvent destabilized the bis(4-methoxyphenyl)methyl cation (photograph (d) in Fig. 1).
Based on the above experiments, a plausible reaction mechanism based on the model reaction is proposed, as illustrated in Fig 2. Water from Fe2(SO4)3·xH2O or from the atmosphere is adsorbed on the surface of the silica gel, and forms hydrogen bonds with the surface hydroxyl groups of the silica, producing hydrophilic cores. The hydroxyl group of a benzhydryl alcohol molecule is attracted to a hydrophilic core through the formation of a hydrogen bond with the hydroxyl group of silica or the adsorbed water. It is then activated to its carbocation catalysed by the Lewis acid Fe2(SO4)3·xH2O. The formed carbocation, which is hydrophobic, then leaves the hydrophilic core and is attacked by a benzoylacetone molecule to form the target compound.
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Fig. 2 A plausible reaction mechanism for Fe2(SO4)3·xH2O on silica catalyzed direct nucleophilic substitution reactions of alcohols. |
Furthermore, the reusability of this catalytic system for direct nucleophilic substitution reactions was also investigated from the point of green chemistry. The results are collected in Table 3. It was found that the supported iron salt, Fe2(SO4)3·xH2O, could be reused without any significant decrease in the catalytic activity. The ‘cross reuse’ experiment showed that the recovered catalyst could be reused for different nucleophiles and alcohols with almost equivalent catalytic performances compared to using the fresh catalyst, suggesting its superior reusability.
In conclusion, this work has developed an efficient catalyst system based on Fe2(SO4)3·xH2O on silica for direct nucleophilic substitution reactions of alcohols. The high conversion and selectivity, wide substrate tolerance, low cost of the catalyst, simple experimental process, solvent-free and benign reaction conditions, and reusability of the catalyst make this method attractive as a green chemistry process. Additionally, the plausible reaction mechanism may give some insight into the construction of novel alcohol activation systems.
Yield: 98%. White solid, m.p. 155–156 °C. 1H NMR (400 MHz, CDCl3) δ: 7.96 (d, J = 8 Hz, 2H), 7.77–7.03 (m, 13H), 5.62 (d, J = 12 Hz, 1H), 5.10 (d, J = 12 Hz, 1H), 2.05 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 202.3, 193.1, 140.6, 140.2, 136.1, 132.5, 128.2, 128.0, 127.9, 127.3, 126.9, 126.6, 125.9, 68.2, 50.1, 27.1. MS (ESI): m/z 328.1.
Footnote |
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c3ra45772a |
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