Feng
Zhao
a,
Bin
Li
a,
Huawen
Huang
a and
Guo-Jun
Deng
*ab
aKey Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China. E-mail: gjdeng@xtu.edu.cn; Fax: +86-0731-5829-2251; Tel: +86-0731-5829-8601
bKey Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China
First published on 26th January 2016
A palladium-catalyzed construction for N-arylsulfonamide from nitroarenes and arylsulfonyl hydrazides is developed. In this protocol, abundant and stable nitroarenes serve as the nitrogen sources by in situ reduction reaction of hydrogen released from arylsulfonyl hydrazides. No external oxidants or reductants are needed for this kind of transformation.
As we known, aromatic nitro compounds can undergo reductive reactions for the preparation of the corresponding arylamines. In recent years, there have been significant attractions to transition-metal-catalyzed C–N bond formations by utilizing nitroarenes as starting materials. The nitroarenes were reduced in situ via borrowing hydrogen strategy (hydrogen transfer)10,11 or by adding external reducing agent.12 We envisioned that it might be rational using nitroarenes instead of aromatic amines as abundant and stable nitrogen sources for the selective construction of S–N bond. Previously, our group demonstrated a series of protocols by harnessing alcohols and nitroarenes to form second amines,13 tertiary amines,14 amides15 and N-containing heterocycles.16 We also reported a palladium-catalyzed one-pot synthesis of diarylamines from nitroarenes and cyclohexanones.17 In these methods, nitroarenes successfully acted as the hydrogen acceptors and were reduced to amines in situ through hydrogen transfer methodology, and no external reductants were needed to the reactions. As part of our continuing efforts in using nitroarenes as the coupling partners to construct C–N and N-hetero bonds, herein, we report a palladium-catalyzed formation of N-arylsulfonamides from nitroarenes and arylsulfonyl hydrazides using the hydrogen transfer strategy (Scheme 1).
We begin our research by investigating the reaction of p-toluenesulfonyl hydrazides (1a) with nitrobenzene (2a) in DMF by using Pd(OAc)2 as catalyst and the desired product was obtained in 19% yield as detected by GC and NMR methods (Table 1, entry 1). Afterwards, a variety of palladium catalysts were examined for this reaction. Similar results were achieved when employing PdCl2, PdBr2, Pd(COD)Cl2 as the catalyst (Table 1, entries 2–4). Pd(acac)2 and Pd(TFA)2 improved the reaction yield to 36% and 35%, respectively (entries 5 and 6). Among the catalysts screened, Pd(OH)2 showed the most effective and afford 3a in 42% yield (entry 7). Solvents also played an important role and the effect of solvents on this transformation was also examined. DMA, NMP and pyridine gave a similar result (entries 8–10). A lower yield was obtained when DMSO was employed as the solvent (entry 11). Unfortunately, when the reaction was conducted in weak polar solvent such as dioxane and toluene, only a trace amount of desired product was acquired under the similar reaction conditions (entries 12 and 13). In order to improve the reaction yield, we attempted to investigate some additives. Encouraged by the result of entry 10, we used 1 equiv. of pyridine as the additive in DMF. To our delight, the yield of 3a was increased to 58% (entry 14). We tested some external reductants such as hydrazine hydrate and isopropanol to enhance the reaction yield, however both of them were not efficient (entries 15 and 16). We proposed that the role of pyridine was acted as a base so we tried organic base triethylamine and inorganic base potassium carbonate, but the results were also unsatisfactory (entries 16–17). Notably, a desired yield could be obtained when the reaction was performed under an argon atmosphere and molecular sieve was added to the reaction system (entries 18–20).
Entry | Catalyst | Additive | Solvent | Yieldb (%) |
---|---|---|---|---|
a Conditions: 1a (0.4 mmol), 2a (0.2 mmol), catalyst (5 mol%), additive (0.2 mmol), solvent (0.8 mL), 90 °C, 20 h under air unless otherwise noted. b GC yield based on 2a. c 100 mg 4 Å molecular sieves was added. d Under argon. | ||||
1 | Pd(OAc)2 | DMF | 19 | |
2 | PdCl2 | DMF | 25 | |
3 | PdBr2 | DMF | 24 | |
4 | Pd(COD)Cl2 | DMF | 42 | |
5 | Pd(acac)2 | DMF | 36 | |
6 | Pd(TFA)2 | DMF | 35 | |
7 | Pd(OH)2 | DMF | 42 | |
8 | Pd(OH)2 | DMF | 36 | |
9 | Pd(OH)2 | NMP | 34 | |
10 | Pd(OH)2 | Pyridine | 37 | |
11 | Pd(OH)2 | DMSO | 23 | |
12 | Pd(OH)2 | Toluene | Trace | |
13 | Pd(OH)2 | Dioxane | Trace | |
14 | Pd(OH)2 | Pyridine | DMF | 58 |
15 | Pd(OH)2 | N2H4·H2O | DMF | Trace |
16 | Pd(OH)2 | i-PrOH | DMF | 19 |
17 | Pd(OH)2 | Et3N | DMF | 21 |
18 | Pd(OH)2 | K2CO3 | DMF | Trace |
19c | Pd(OH)2 | Pyridine | DMF | 66 |
20d | Pd(OH)2 | Pyridine | DMF | 72 |
21c,d | Pd(OH)2 | Pyridine | DMF | 84 |
With the optimized reaction conditions in hand, we explored the scope of this transformation. As presented in Table 2, a variety of arylsulfonyl hydrazides were successfully reacted with nitrobenzene (2a) to produce corresponding N-arylsulfonamides in moderate to good yields. Generally, alkyl substituents at the para position of sulfonyl hydrazide slightly affected the reaction yield (3a–3d). Functional groups such as halogens and trifluoromethoxy were well tolerated under the optimal reaction conditions (3e–3h). It should be noted that cleavage of C-halogen bond was not observed during the reaction process. When ortho-substituted arylsulfonyl hydrazides reacted with nitrobenzene, relatively lower yields were obtained probably due to the steric effect of the substituents (3i-3j).
a Conditions: 1 (0.4 mmol), 2a (0.2 mmol), Pd(OH)2 (5 mol%), pyridine (0.2 mmol), DMF (0.8 mL), 4 Å MS (100 mg), 90 °C, 20 h, under argon; isolated yield based on 2a. |
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Subsequently, a number of substituted nitroarenes were employed to react with p-toluenesulfonyl hydrazide and the results are shown in Table 3. Methyl and methoxy nitrobenzenes reacted smoothly with 1a to give the corresponding products in reasonable yields (3k–3m). Halogen substituents such as trifluoromethyl, fluoro and chloro were well tolerated under the optimized reaction conditions, and the target products were obtained in good yields (3n–3s). Other substrates bearing electron-withdrawing group such as cyano remained effective and gave the corresponding arylsulfonamides in good yields (3t–3u). Notably, when 1-(2-nitrophenyl)ethanone was subjected to this reaction system, the desired product could be achieved in 70% yield (3v). Finally, a more steric bulky substrate such as 1-nitronaphthelene also successfully afforded the product in 71% yield (3w).
a Conditions: 1a (0.4 mmol), 2 (0.2 mmol), Pd(OH)2 (5 mol%), pyridine (0.2 mmol), DMF (0.8 mL), 4 Å MS (100 mg), 90 °C, 20 h, under argon; isolated yield based on 2. |
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For the mechanism of this transformation, we proposed a catalytic process that includes the following steps (Scheme 2). The reaction of arylsulfonyl hydrazide with a Pd catalyst results in a Pd complex A and sulfonyl diazene 3, which is formed through successive hydrogen transferring and β-hydride elimination. In the presence of a Pd catalyst, liberation of N2 and H+ from 3 leads to the formation of arylsulfonylpalladium B.18 On the other hand, nitrobenzene is reduced to nitrosobenzene with the help of complex A.17,19 Then, the reaction of complex B with nitrosobenzene gives N-arylsulfonyl-N-phenylhydroxyamine 6. At last, hydrogenation of 6 affords the desired product and regenerates the Pd catalyst.
To gain a mechanistic insight, deuterium labelling experiments were conducted and the results were summarized in Scheme 3. When TsNDND2 (ref. 20) (1a–D) reacted with 2a under the standard reaction conditions, N-deuterated product was obtained (Scheme 3, eqn (1)). When 1a reacted with 2a in the presence of D2O, no deuterated product 3a was observed (Scheme 3, eqn (2)). Treatment of 3a with D2O led to 3a recovered and no deuterated 3a was obtained (Scheme 3, eqn (3)). These results indicated that the hydrogen transfer process very likely proceeded according to the proposed mechanism.
Footnote |
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra26588f |
This journal is © The Royal Society of Chemistry 2016 |