Int. J. Mol. Sci. 2013, 14(9), 18850-18860; doi:10.3390/ijms140918850

Article
A Facile and Efficient Synthesis of Diaryl Amines or Ethers under Microwave Irradiation at Presence of KF/Al2O3 without Solvent and Their Anti-Fungal Biological Activities against Six Phytopathogens
Liang-Zhu Huang 1,, Pan Han 1,, You-Qiang Li 1, Ying-Meng Xu 1, Tao Zhang 1 and Zhen-Ting Du 1,2,*
1
College of Science, Northwest A & F University, Yangling 712100, China; E-Mails: hlz15106006@163.com (L.-Z.H.); hanpan_093@163.com (P.H.); lyq812322926@163.com (Y.-Q.L.); dirk41414141@126.com (Y.-M.X.); fuzitong@163.com (T.Z.)
2
Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 20032, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed; E-Mail: duzt@nwsuaf.edu.cn; Tel./Fax: +86-29-8709-2226.
Received: 8 July 2013; in revised form: 5 September 2013 / Accepted: 6 September 2013 /
Published: 12 September 2013

Abstract

: A series of diaryl amines, ethers and thioethers were synthesized under microwave irradiation efficiently at presence of KF/Al2O3 in 83%–96% yields without any solvent. The salient characters of this method lie in short reaction time, high yields, general applicability to substrates and simple workup procedure. At the same time, their antifungal biological activities against six phytopathogen were evaluated. Most of the compounds (3b, 3c, 3go) are more potent than thiophannate-methyl against to Magnaporthe oryzae. This implies that diaryl amine or ether moiety may be helpful in finding a fungicide against Magnaporthe oryzae.
Keywords:
microwave-assisted organic synthesis; diaryl amine; diaryl ether; KF/Al2O3

1. Introduction

Microwave-assisted organic synthesis (MAOS) has been one of the most exciting areas of interest on which many reviews have been published in last three decades [14]. Numerous reactions, including condensations [58], cycloadditions [912], heterocycles formations [1315], and metal catalyzed cross-coupling [16,17] have been explored under microwave conditions. Some of these have been applied to medicinal chemistry and total syntheses of natural products [1820]. MAOS can facilitate the discovery of new reactions and reduce cycle time in optimization of reactions. In addition, it serves to expand chemical space in compound library synthesis.

Diaryl heteratom moities can be found from natural products, pharmaceuticals or optical materials [21,22] (Figure 1). Traditionally, they are prepared through a copper-assisted Ullmann reaction by intermolecular SNAr way. However, the key concerns of this chemical operation are harsh conditions (reaction temperature >200 °C) and troublesome residue stemming from a stoichiometric amount of copper [23] in terms of chemical waste. Palladium and copper complexes with various kinds of ligands have been studied fully for the cross-coupling between heteroatom (N, O, S) with aryl halide [2427]. Transition metal catalysis (including Cu [28], Ni [29,30], Fe [3133]) are involved as a complementary means of cross-coupling. However, the researchers still are confronted with the cost of precious metal and metal residue in products. In our pursuing new heterocyclic structures which serve as potential bioactive compounds in agriculture, we discovered a new palladium catalyzed cyclization of diazonium salts to form dibenzo[d]furan [34] and 6H-benzo[c]chromenes [35]. In preparing the substrates of such kinds of reaction patterns, we need to rapidly obtain a quantity of the derivatives of diaryl amine, ether and thioether. The existing methods in the literature seem tedious, laborious or not applicable. Therefore, there is still a need for innovation in such a general chemical transformation in order to provide corresponding structures effectively and on a feasible scale. Herein, we wish to report an improved method in preparation of these kinds of substrates under microwave irradiation.

2. Results and Discussion

Initially, the o-nitro chlorobezene and aniline were chosen as starting materials of model reaction. Thus, the different bases and solvents were also involved in this test and the results are summarized in Table 1. The reaction was performed in polar non-protonic solvent and at presence of K2CO3 as base in refluxing temperature. To our regret, the conversion rate of both were below 45%, even after 12 h. Following this, we introduced microwave irradiation to the system: the conversion rate increased considerably. Then, several bases such as (K2CO3Table 1, entry 3, NaOH, entry 5, KF/Al2O3 entry 8 and without base entries 6 and 7) were screened under microwave irradiation. Na2CO3 did not show a positive effect on this conversion and NaOH showed a worse result. We suspected that the complication of the products was due to the high concentration of NaOH which will attack chloride directly. The solvent-free system was also performed and the yield is higher than in DMF because of the latter’s higher reaction temperature. Finally, a composite solid base KF/Al2O3 was chosen as the best catalyst for this reaction. A literature survey revealed that KF/Al2O3 showed wide spectrum applications in base catalyzed reactions [3638].

Under these optimized reaction conditions, we next examined the scope of KF/Al2O3 catalyzed coupling of o-nitrophenylchloride 1 and a wide spectrum of substrates such as amines, phenols and thiophenols 2 for the synthesis of substituted analogues of diphenyl amine. The results are summarized in Table 2. A wide range of structurally diverse amines, phenols, and thiophenols (Table 2) can be coupled with o-nitrohalobenzene under this protocol to give the corresponding substituted diaryl hetero ethers in excellent yields. It should be noted that the reactants need preheat to melt before microwave irradiation. Among them, bromo (Table 2, entries 4 and 9) and chloro (Table 2, entries 5 and 14) groups can be tolerated. The bromo and chloro moieties could be functionalized to boric acid or stannane easily, so our method effectively allows the preparation of halo diaryl hetero ethers. Thus, all the products in our reactions listed in Table 2 were easily characterized on the basis of physical and spectral data and also by comparison with authentic samples. All products (Table 2) were fully characterized by spectroscopic methods, as well as by the comparison of the spectral data with reported values.

Having obtained these 15 compounds, their antifungal activities (3ao) against six phytopathogenic fungi (i.e., Cytospora mandshurica, Curvularia lunata, Magnaporthe oryzae, Gloeosporium fructigenum, Alternaria alternate, Fusarium graminearum) were investigated at the concentration of 100 μg/mL in vitro by poisoned food technique [39]. Thiophanate-methyl, which is structurally similar to these compounds and a commercially available agricultural fungicide, was used as a positive control at 100 μg/mL. For each treatment, three replicates were conducted. The radial growths of the fungal colonies were measured and the data were statistically analyzed. The inhibitory effects of the test compounds on these fungi in vitro were calculated by the formula:

Inhibition rate  ( % ) = ( C - T ) × 100 / C

where C represents the diameter of fungi growth on untreated Potato Dextrose Agar (PDA), and T represents the diameter of fungi on treated PDA.

As outlined in Table 3, all the analogues of diaryl amine (entries 3ag) showed only fairly good antifungal activities comparing with thiophannate-methyl. As for Alternaria lternata and Fusarium graminearum, compounds (3a, 3df), they show unsatisfactory activity. As for compounds 3df, they were almost inactive to the phytopathogenic fungi. Diaryl ethers (entries 3hk) also showed only fairly good antifungal activities. It should be noted that the inhibition rate of 3h to Curvularia lunata is as high as 62.67%, compared with the one of thiophannate-methyl, 37.95%. As for diaryl thioethers (3lo), they showed moderate antifungi bioactivities. On the other hand, most of the compounds (entries 3b, 3c, 3go) are more potent than thiophannate-methyl against Magnaporthe oryzae. This implies that diaryl moiety may be more helpful in fungicide against Magnaporthe oryzae.

3. Experimental Section

3.1. Typical Synthetic Procedure

A well dispensed mixture of 2-nitrochloro benzene (10 mmol), aniline (10 mmol) and KF/Al2O3 (2 g) was vigorously stirred and irradiated in microwave reactor (Sineo MAS-II, Shanghai, China) at internal temperature 150 °C for 15 min. Then the reaction mixture was diluted by dichloro methane (60 mL) and the organic layer was washed by saturated aqueous NaHCO3 and brine, and dried with anhydrous MgSO4. The solvent was evaporated in vacuum and the residue was purified through column chromatography to give 3 (Table 2). The 1H-NMR and 13C-NMR data were recorded in deutrated chloroform solution with NMR spectrometers (DRX 500, Bruker, Billerica, Massachusetts) if not noted otherwise. The chemical shifts are measured relative to tetramethylsilane (TMS) (δ = 0) or chloroform (δ = 7.26) and the coupling J is expressed in Hertz.

3.1.1. 2-Nitrodiphenylamine (3a)

Orange solid, mp 74–76 °C (lit. [40], 76–77 °C). 1H-NMR: 9.50 (s, 1H), 8.20 (dd, 1H, J = 7.2, 1.4), 7.35–7.45 (m, 3H), 7.20–7.30 (m, 4H), 6.78 (t, 1H, J = 6.9); 13C-NMR: 143.0, 137.9, 134.8, 132.4, 129.7, 126.8, 125.4, 124.4, 117.5, 116.1.

3.1.2. 4′-Methl-2-nitrodiphenylamine (3b)

Orange solid, mp 69–70 °C (lit. [41], 69–70 °C). 1H-NMR: 2.38 (s, 3H), 6.73 (t, 1H, J = 7.8), 7.13–7.16 (m, 3H), 7.22 (d, 2H, J = 8.3), 7.33 (t, 1H, J = 6.6), 8.19 (dd, 1H, J = 8.6, J = 1.4), 9.45 (s, 1H). 13C-NMR: 21.0, 116.0, 117.1, 124.8, 126.7, 130.3, 132.8, 135.7, 135.8, 135.9, 143.7.

3.1.3. 4′-Methoxy-2-nitrodiphenylamine (3c)

Orange solid, mp 88–89 °C (lit. [40,41], 87–88 °C). 1H-NMR: 9.41 (s, 1H), 8.19 (d, 1H, J = 8.6), 7.30 (t, 1H, J = 7.9), 7.20 (d, 2H, J = 8.3), 6.90–7.15 (m, 3H), 6.71 (t, 1H, J = 7.7), 3.84 (s, 3H). 13C-NMR: 157.7, 144.2, 135.6, 132.5, 131.1, 127.3, 126.5, 116.8, 115.6, 114.7, 55.6.

3.1.4. 4′-Bromo-2-nitrodiphenylamine (3d)

Orange solid, mp 170–171 °C (lit. [40,41], 168–169 °C). 1H-NMR: 6.81 (t, 1H, J = 7.8), 7.15–7.21 (m, 3H), 7.39 (t, 1H, J = 7.8), 7.52 (d, 2H, J = 8.6), 8.21 (dd, 1H, J = 1.4, J = 8.6), 9.39 (s, 1H). 13C-NMR: 115.9, 115.9, 118.1, 118.4, 125.7, 126.8, 132.8, 135.8, 137.9, 142.4.

3.1.5. 4′-Chloro-2-nitrodiphenylamine (3e)

Orange solid, mp 170–171 °C (lit. [41], 168–169 °C). 1H-NMR (500 MHz, CDCl3): 6.83 (t, 1H, J = 8.0), 7.15–7.32 (m, 3H), 7.35–7.45 (m, 3H), 8.24 (dd, 1H, J = 8.6, 1.5). 13C-NMR: 115.9, 118.0, 121.5, 125.6, 126.9, 129.3, 130.1, 135.7, 142.4, 144.1.

3.1.6. 2,4-Dinitrodiphenylamine (3f)

Orange solid, mp 158–159 °C (lit. [42], 156–157 °C). 1H-NMR: 7.17 (d, 1H, J = 9.6), 7.32 (d, 2H, J = 7.7), 7.39 (t, 1H, J = 7.4), 7.52 (t, 2H, J = 7.7), 8.17 (dd, 1H, J = 2.6, J = 9.6), 9.17 (d, 1H, J = 2.6), 9.99 (s, 1H). 13C-NMR: 116.1, 124.1, 125.5, 127.8, 129.9, 130.3, 131.1, 136.7, 137.4, 147.1.

3.1.7. 2′-Methyl-2,4-dinitrodiphenylamine (3g)

Orange solid, mp 123–124 °C (lit. [43], 124–126 °C). 1H-NMR: 2.27 (s, 3H), 6.83 (d, 1H, J = 9.6), 7.28 (d, 1H, J = 3.6), 7.34 (dd, 2H, J = 3.6, J = 5.6), 7.39 (t, 1H, J = 4.8), 8.15 (dd, 1H, J = 2.6, J = 9.5), 9.19 (d, 1H, J = 2.6), 9.83 (s, 1H). 13C-NMR: 17.9, 115.9, 124.2, 126.8, 127.7, 128.5, 130.0, 130.8, 131.9, 134.9, 135.1, 137.2, 147.5.

3.1.8. 2-Nitrophenyl phenyl ether (3h)

Yellowish oil, 1H-NMR: δ = 8.29 (dd, 1H, J = 8.6, 1.4), 7.85 (dd, 1H, J = 8.3, 2.3), 7.35–7.45 (m, 3H), 7.20–7.30 (m, 4H). 13C-NMR: 157.1, 149.9, 139.5, 134.2, 129.7, 123.5, 122.2, 118.0, 117.3.

3.1.9. 4′-Bromophenyl-2-nitrophenyl ether (3i)

Yellow solid, mp 68–69 °C (lit. [44], 71 °C). 1H-NMR: 6.92 (dd, 2H, J = 2.1, J = 6.8), 7.04 (dd, 1H, J = 1.0, J = 8.4), 7.25 (t, 1H, J = 7.6), 7.48 (dd, 2H, J = 2.1, J = 6.8), 7.54 (t, 1H, J = 8.0), 7.96 (dd, 1H, J = 1.6, J = 8.2). 13C-NMR: 117.2, 120.6, 120.9, 123.9, 125.9, 133.1, 134.3, 150.0, 155.2.

3.1.10. 4′-Methylphenyl-2-nitrophenyl ether (3j)

Yellow oil, 1H-NMR: 7.92–7.96 (m, 1H), 7.45–7.50 (m, 1H), 7.10–7.20 (m, 3H), 6.95–7.00 (m, 3H), 2.37 (s, 3H); 13C-NMR: 153.7, 151.7, 141.5, 134.8, 134.4, 131.0, 126.1, 123.0, 120.2, 119.8, 21.2.

3.1.11. 4′-Methoxyphenyl-2-nitrophenyl ether (3k)

Yellow solid, mp 47–48 °C (lit., 48 °C). 1H-NMR: 3.81 (s, 3H), 6.91 (dd, 3H, J = 2.4, J = 6.8), 7.02 (dd, 2H, J = 2.3, J = 6.8), 7.12 (t, 1H, J = 7.7), 7.44 (t, 1H, J = 7.7), 7.92 (dd, 1H, J = 1.6, J = 8.2). 13C-NMR: 55.7, 115.1, 118.9, 121.2, 122.2, 125.7, 134.0, 140.7, 148.6, 151.9, 156.8.

3.1.12. 2-Nitrodiphenylthioether (3l)

Yellow solid, mp 81–82 °C (lit. [45], 80 °C). 1H-NMR: 6.86 (dd, 1H, J = 1.1, J = 8.2), 7.21 (t, 1H, J = 7.7), 7.34 (t, 1H, J = 7.7), 7.48–7.50 (m, 3H), 7.58 (dd, 2H, J = 1.9, J = 5.0), 8.22 (dd, 1H, J = 1.4, J = 8.3). 13C-NMR: 125.0, 125.8, 128.3, 130.1, 130.2, 131.0, 133.5, 136.0, 139.5, 144.9.

3.1.13. 4′-Methyl-2-nitrodiphenylthioether (3m)

Yellow solid, mp 88–90 °C (lit. [45], 88 °C). 1H-NMR: 2.43 (s, 3H), 6.85 (dd, 1H, J = 1.0, J = 8.2), 7.19 (t, 1H, J = 7.7), 7.28–7.35 (m, 3H), 7.46 (d, 2H, J = 8.0), 8.22 (dd, 1H, J = 1.2, J = 9.3). 13C-NMR: 21.4, 124.8, 125.8, 127.3, 128.1, 131.0, 133.4, 136.0, 140.1, 140.5, 144.8.

3.1.14. 4′-Chloro-2-nitrodiphenylthioether (3n)

Yellow solid, mp 95–96 °C (lit. [45], 94 °C). 1H-NMR: 6.86 (dd, 1H, J = 1.1, J = 8.2), 7.24 (t, 1H, J = 7.8), 7.37 (t, 1H, J = 7.7), 7.46 (dd, 2H, J = 2.2, J = 8.8), 7.52 (dd, 2H, J = 2.0, J = 6.5), 8.23 (dd, 1H, J = 1.4, J = 8.2). 13C-NMR: 125.3, 125.9, 128.2, 129.6, 130.4, 133.6, 136.5, 137.2, 138.8, 145.1.

3.1.15. 4′-Methyl-4-chloro-2-nitrodiphenylthioether (3o)

Yellow solid, mp 119–120 °C (lit. [46], 121 °C). 1H-NMR: 2.43 (s, 3H), 6.78 (d, 1H, J = 8.8), 7.30 (d, 3H, J = 7.6), 7.45 (d, 2H, J = 8.0), 8.21 (d, 1H, J = 2.3). 13C-NMR: 21.4, 125.5, 126.7, 129.3, 130.5, 130.6, 130.9, 131.1, 133.5, 135.9, 138.9, 140.8, 144.8.

4. Conclusions

In conclusion, a practical KF/Al2O3 catalyzed synthesis analogue of diaryl heteroatom moties under MWI has been developed. This method offers several advantages, such as high yields, short reaction times, clean reaction profiles, and simple experimental and easy work-up procedures. Fifteen products were tested against six phytopathogenic fungi and their preliminary SAR were analyzed.

Acknowledgments

National Natural Science Foundation of China (31270388) and Financial support from the Fundamental Research Funds for the Central Universities in NWSUAF as well as Financial support from the open funding of Key Laboratory of Synthetic Chemistry of Natural Substances of SIOC the is greatly appreciated. We are grateful to Special Fund for Forestry Scientific Research in Public Interest (No. 200904004) for partial support of this work.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Kappe, C.O. Controlled microwave heating in modern organic synthesis. Angew. Chem. Int. Ed 2004, 43, 6250–6284.
  2. Kappe, C.O.; Dallinger, D. The impact of microwave synthesis on drug discovery. Nat. Rev. Drug Discov 2006, 5, 51–63.
  3. Lidstrom, P.; Tierney, J.; Wathey, B.; Westman, J. Microwave assisted organic synthesis—A review. Tetrahedron 2001, 57, 9225–9283.
  4. Shipe, W.D.; Wolkenberg, S.E.; Lindsley, C.W. Accelerating lead development by microwave-enhanced medicinal chemistry. Drug Discov. Today 2005, 2, 155–161.
  5. Mallouk, S.; Bougrin, K.; Laghzizil, A.; Benhida, R. Microwave-assisted and efficient solvent-free knoevenagel condensation. A sustainable protocol using porous calcium hydroxyapatite as catalyst. Molecules 2010, 15, 813–823.
  6. Mukhopadhyay, C.; Datta, A.; Banik, B.K. Microwave-induced perchloric acid catalyzed novel solvent-free synthesis of 4-aryl-3,4-dihydropyrirnidones via Biginelli condensation. J. Heterocycl. Chem 2007, 44, 979–981.
  7. Al-Zaydi, K.M.; Borik, R.M. Microwave assisted condensation reactions of 2-aryl hydrazonopropanals with nucleophilic reagents and dimethyl acetylenedicarboxylate. Molecules 2007, 12, 2061–2079.
  8. Shaabani, A.; Teimouri, M.B.; Samadi, S.; Soleimani, K. Microwave-assisted three-component condensation on montmorillonite K10: Solvent-free synthesis of furopyrimidines, furocoumarins, and furopyranones. Synth. Commun 2005, 35, 535–541.
  9. Margetic, D.; Troselj, P.; Murata, Y. Microwave-accelerated ruthenium-catalyzed [2π + 2π] cycloadditions of dimethylacetylene dicarboxylate with norbornenes. Synth. Commun 2011, 41, 1239–1246.
  10. Linder, I.; Gerhard, M.; Schefzig, L.; Andra, M.; Bentz, C.; Reissig, H.U.; Zimmer, R. A modular synthesis of functionalized pyridines through lewis-acid-mediated and microwave-assisted cycloadditions between azapyrylium intermediates and alkynes. Eur. J. Org. Chem 2011, 2011, 6070–6077.
  11. Dong, S.W.; Cahill, K.J.; Kang, M.I.; Colburn, N.H.; Henrich, C.J.; Wilson, J.A.; Beutler, J.A.; Johnson, R.P.; Porco, J.A. Microwave-based reaction screening: Tandem retro-Diels Alder/Diels-Alder cycloadditions of o-quinol dimers. J. Org. Chem 2011, 76, 8944–8954.
  12. Tsai, C.W.; Yang, S.C.; Liu, Y.M.; Wu, M.J. Microwave-assisted cycloadditions of 2-alkynylbenzonitriles with sodium azide: Selective synthesis of tetrazolo[5,1-a]pyridines and 4,5-disubstituted-2H-1,2,3-triazoles. Tetrahedron 2009, 65, 8367–8372.
  13. Wang, S.L.; Zhang, G.; Jie, D.; Jiang, B.; Wang, X.H.; Tu, S.J. Microwave-assisted multicomponent reactions: Rapid and regioselective formation of new extended angular fused aza-heterocycles. Comb. Chem. High Throughput Screen 2012, 15, 400–410.
  14. Sharma, A.; Appukkuttan, P.; van der Eycken, E. Microwave-assisted synthesis of medium-sized heterocycles. Chem. Commun 2012, 48, 1623–1637.
  15. Mancini, P.M.E.; Ormachea, C.M.; Della Rosa, C.D.; Kneeteman, M.N.; Suarez, A.G.; Domingo, L.R. Ionic liquids and microwave irradiation as synergistic combination for polar Diels-Alder reactions using properly substituted heterocycles as dienophiles. A DFT study related. Tetrahedron Lett 2012, 53, 6508–6511.
  16. Appukkuttan, P.; van der Eycken, E. Recent developments in microwave-assisted, transition-metal-catalysed C–C and C–N bond-forming reactions. Eur. J. Org. Chem 2008, 2008, 1133–1155.
  17. Nilsson, P.; Ofsson, K.; Larhed, M. Microwave-Assisted and Metal-Catalyzed Coupling Reactions. In Microwave Methods in Organic Synthesis; Larhed, M., Olofsson, K., Eds.; Springer: New York, NY, USA, 2006; Volume 266, pp. 103–144.
  18. Hughes, R.A.; Thompson, S.P.; Alcaraz, L.; Moody, C.J. Total synthesis of the thiopeptide amythiamicin D. Chem. Commun. 2004, 946–948.
  19. Baxendale, I.R.; Ley, S.V.; Piutti, C. Total synthesis of the amaryllidaceae alkaloid (+)-plicamine and its unnatural enantiomer by using solid-supported reagents and scavengers in a multistep sequence of reactions. Angew. Chem. Int. Ed 2002, 41, 2194–2197.
  20. Baran, P.S.; O’Malley, D.P.; Zografos, A.L. Sceptrin as a potential biosynthetic precursor to complex pyrrole–imidazole alkaloids: The total synthesis of ageliferin. Angew. Chem. Int. Ed 2004, 43, 2674–2677.
  21. Evano, G.; Blanchard, N.; Toumi, M. Copper-mediated coupling reactions and their applications in natural products and designed biomolecules synthesis. Chem. Rev 2008, 108, 3054–3131.
  22. Corbet, J.-P.; Mignani, G. Selected patented cross-coupling reaction technologies. Chem. Rev 2006, 106, 2651–2710.
  23. Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Aryl–aryl bond formation one century after the discovery of the Ullmann reaction. Chem. Rev 2002, 102, 1359–1469.
  24. Hartwig, J.F. Transition metal catalyzed synthesis of arylamines and aryl ethers from aryl halides and triflates: Scope and mechanism. Angew. Chem. Int. Ed 1998, 37, 2046–2067.
  25. Fernandez-Rodriguez, M.A.; Shen, Q.; Hartwig, J.F. A general and long-lived catalyst for the palladium-catalyzed coupling of aryl halides with thiols. J. Am. Chem. Soc 2006, 128, 2180–2181.
  26. Wolfe, J.P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S.L. Rational development of practical catalysts for aromatic carbon-nitrogen bond formation. Acc. Chem. Res 1998, 31, 805–818.
  27. Frlan, R.; Kikelj, D. Recent progress in diaryl ether synthesis. In Synthesis; 2006; pp. 2271–2285.
  28. Jammi, S.; Sakthivel, S.; Rout, L.; Mukherjee, T.; Mandal, S.; Mitra, R.; Saha, P.; Punniyamurthy, T. CuO nanoparticles catalyzed C–N, C–O, and C–S cross-coupling reactions: Scope and mechanism. J. Org. Chem 2009, 74, 1971–1976.
  29. Wolfe, J.P.; Buchwald, S.L. Nickel-catalyzed amination of aryl chlorides. J. Am. Chem. Soc 1997, 119, 6054–6058.
  30. Jammi, S.; Barua, P.; Rout, L.; Saha, P.; Punniyamurthy, T. Efficient ligand-free nickel-catalyzed C–S cross-coupling of thiols with aryl iodides. Tetrahedron Lett 2008, 49, 1484–1487.
  31. Bistri, O.; Correa, A.; Bolm, C. Iron-catalyzed C–O cross-couplings of phenols with aryl iodides. Angew. Chem. Int. Ed 2008, 47, 586–588.
  32. Correa, A.; Bolm, C. Iron-catalyzed N-arylation of nitrogen nucleophiles. Angew. Chem. Int. Ed 2007, 46, 8862–8865.
  33. Correa, A.; Carril, M.; Bolm, C. Iron-catalyzed S-arylation of thiols with aryl iodides. Angew. Chem. Int. Ed 2008, 47, 2880–2883.
  34. Du, Z.T.; Zhou, J.; Si, C.M.; Ma, W.L. Synthesis of dibenzofurans by palladium-catalysed tandem denitrification/C–H activation. Synlett 2011, 3023–3025.
  35. Zhou, J.; Huang, L.-Z.; Li, Y.-Q.; Du, Z.-T. Synthesis of substituted 6H-benzo[c]chromenes: A palladium promoted ring closure of diazonium tetrafluoroborates. Tetrahedron Lett 2012, 53, 7036–7039.
  36. Villemin, D.; Alloum, A.B. Potassium fluoride on alumina: Oxidative coupling of acidic carbon compounds with diiodine. Synth. Commun 1992, 22, 3169–3179.
  37. Kabalka, G.W.; Wang, L.; Pagni, R.M. Microwave enhanced glaser coupling under solvent free conditions. Synlett 2001, 2001, 0108–0110.
  38. Kabalka, G.W.; Wang, L.; Namboodiri, V.; Pagni, R.M. Rapid microwave-enhanced, solventless Sonogashira coupling reaction on alumina. Tetrahedron Lett 2000, 41, 5151–5154.
  39. Erwin, D.C.; Sims, J.J.; Borum, D.E.; Childers, J.R. Detection of the systemic fungicide, thiabendazole, in cotton plants and soil by chemical analysis and bioassay. Phytopathology 1971, 61, 964–967.
  40. Rao, H.; Jin, Y.; Fu, H.; Jiang, Y.; Zhao, Y. A versatile and efficient ligand for copper-catalyzed formation of C–N, C–O, and P–C bonds: Pyrrolidine-2-phosphonic acid phenyl monoester. Chem. Eur. J 2006, 12, 3636–3646.
  41. Guo, Z.-R.; Xu, Z.-B.; Lu, Y. An efficient and fast procedure for the preparation of 2-nitrophenylamines under microwave conditions. Synlett 2003, 2003, 564–566.
  42. Singh, R.; Allam, B.K.; Raghuvanshi, D.S.; Singh, K.N. Cooperatively assisted N-arylation using organic ionic base–Brønsted acid combination under controlled microwave heating. Tetrahedron 2013, 69, 1038–1042.
  43. Gulevskaya, A.V.; Tyaglivaya, I.N.; Verbeeck, S.; Maes, B.U.W.; Tkachuk, A.V. Oxidative arylamination of 1,3-dinitrobenzene and 3-nitropyridine under anaerobic conditions: The dual role of the nitroarenes. Arkivoc 2011, 2011, 238–251.
  44. Bandna Guha, N.R.; Shil, A.K.; Sharma, D.; Das, P. Ligand-free solid supported palladium(0) nano/microparticles promoted C–O, C–S, and C–N cross coupling reaction. Tetrahedron Lett. 2012, 53, 5318–5322.
  45. Liu, C.; Zang, X.; Yu, B.; Yu, X.; Xu, Q. Microwave-promoted TBAF-catalyzed SNAr reaction of aryl fluorides and ArSTMS: An efficient synthesis of unsymmetrical diaryl thioethers. Synlett 2011, 2011, 1143–1148.
  46. El-Ezbawy, S.R.; Atta, F.M. Reaction on thin-layer-chromatography plates: Formation of sulfides. Indian J. Chem. Sect. B 1989, 28, 690–691.
Ijms 14 18850f1 200
Figure 1. Representive diaryl heteroatom molecules.

Click here to enlarge figure

Figure 1. Representive diaryl heteroatom molecules.
Ijms 14 18850f1 1024
Table Table 1. Screen conditions in diaryl amine formation a.

Click here to display table

Table 1. Screen conditions in diaryl amine formation a.
Ijms 14 18850f2

EntryBaseSolventMWI/HeatYield(%) b
1K2CO3DMFHeat to 80 °C30
2K2CO3DMAHeat to reflux42
3K2CO3DMFMWI 15 min c75
4Na2CO3DMFMWI 15 min c62
5NaOHDMFMWI 15 min c47
6noneDMFMWI 15 min c35
7nonenoneMWI 15 min c56
8KF/Al2O3noneMWI 15 min c92 b

aThe reaction was performed at molar ratio of compound 1 and 2 at 1:1;bIsolated yields;cThe internal temperature was set as 150 °C on a MAS-II microwave reactor; DMF: N,N-dimethylformamide; DMA: N,N-dimethylacetamide; MWI: microwave irradiation.

Table Table 2. Synthesis of diaryl hetero atom moieties under MWI and KF/Al2O3a.

Click here to display table

Table 2. Synthesis of diaryl hetero atom moieties under MWI and KF/Al2O3a.
Ijms 14 18850f3

EntryR1R2R3Product 3Yield (%) b
1HHH Ijms 14 18850f4
3a
92.3 c, 93.5 d
2HMeH Ijms 14 18850f5
3b
94.2 c
3HMeOH Ijms 14 18850f6
3c
100 c,d
4HBrH Ijms 14 18850f7
3d
85.2 c, 87.0 d
5HClH Ijms 14 18850f8
3e
83.7 c
6NO2HH Ijms 14 18850f9
3f
93.8 d
7NO2HMe Ijms 14 18850f10
3g
95.4 d
8HHH Ijms 14 18850f11
3h
91.7 d
9HBrH Ijms 14 18850f12
3i
89.5 c, 91.6 d
10HMeH Ijms 14 18850f13
3j
96.2 c,d
11HOMeH Ijms 14 18850f14
3k
99.0 c,d
12HHH Ijms 14 18850f15
3l
94.4 c
13HMeH Ijms 14 18850f16
3m
97.7 c
14HClH Ijms 14 18850f17
3n
89.4 d
15ClMeH Ijms 14 18850f18
3o
94.7 c

aThe reaction was performed at molar ratio of compound 1 and 2 at 1:1;bisolated yield;c2-nitrochlorobenzene were used;d2-nitrofluorobenzene were used.

Table Table 3. Antifungal activities of 3ao to six phytopathogenic fungi.

Click here to display table

Table 3. Antifungal activities of 3ao to six phytopathogenic fungi.
Antifungal activities (inhibition%)

CompoundCytospora mandshuricaCurvularia lunataMagnaporthe oryzaeGloeosporium fructigenumAlternaria lternataFusarium graminearum
3a41.966.652.1011.940.000.00
3b38.867.2339.3032.1425.4312.79
3c18.5647.6038.6424.7730.5225.46
3d0.0019.300.000.000.000.00
3e9.850.001.370.000.000.00
3f0.000.000.0019.260.000.00
3g16.0740.3737.2425.7055.9528.11
3h29.0362.6721.3952.2815.2617.51
3i31.0837.3714.4814.6930.5235.03
3j24.1717.8920.4521.7430.1210.75
3k21.2614.4624.8224.7727.060.00
3l13.9945.8031.0323.8942.3510.95
3m48.1822.3044.8533.960.1234.31
3n19.7040.9828.9633.0316.890.00
3o58.7644.4648.7539.7328.7142.31
Thiophannate-methyl72.5537.9512.4173.4274.5782.11
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert