Indian Journal of Chemistry Vol. 51B, February 2012, pp. 362-365
Microwave-enhanced triton B catalyzed Suzuki coupling reaction H M Meshram*, B R V Prasad, D A Kumar & B Ch K Reddy Discovery Laboratory, Organic Chemistry Division – I, Indian Institute of Chemical Technology, Hyderabad 500 007, India E-mail:
[email protected] Received 26 October 2010; accepted (revised) 29 November 2011 An efficient method for Suzuki coupling of aryl and hetero aryl halides with aryl and hetero aryl boronic acids using triton B as a base under microwave irradiation is described. Rapid reactions, green solvent and simple isolation procedure are notable features of the protocol Keywords: Triton B, Suzuki coupling, microwave, palladium, aryl halides, hetero aryl boronic acids
The palladium-catalyzed Suzuki coupling reaction of aryl halides with aryl boronic acids for the construction of aryl-aryl bond is one of the most general and powerful tools for the synthesis of pharmaceuticals, natural products, ligands for catalysis and advanced materials1. The classical Suzuki coupling has been reported with aryl halide and boronic acid in the presence of strong base2. Recently, Hoshi and Hagiwara reported Suzuki coupling of aryl chlorides3. The coupling reaction of N-hetero aryl and normal aryl chlorides with thiophene- and furan boronic acids has been reported using complex ligands4 with longer reaction time (14 hr). In case of sterically hindered biaryls, the addition of strong base remarkably enhance the rate of coupling. Subsequently, thalium hydroxide in DMF reported for the synthesis of hindered biaryls5. Ultrasound has also been shown to enhance the coupling of aryl halide in biphasic system using benzyl triethyl ammonium bromide as PTC6. Though the reported methods proved with incremental success, in view of green chemistry these methods have drawbacks of using corrosive and toxic metal hydroxides or phosphates, higher boiling solvents or carcinogenic solvents which are detrimental to environment. However, because of its unique importance of the reaction there has been continuing interest to replace strong and corrosive bases with alternate and safe base. Triton B (benzyl trimethyl ammonium hydroxide) has been used as efficient and non-metallic base in alkylation, oxime ethers preparation, Michael type addition, nitroaldol condensation7. It has been proven recently that microwave heating improves the preparative
efficiency and reduces the reaction time for several organic transformations8. Following our interest in the development of greener synthetic methodologies9, herein we report Suzuki coupling reaction utilizing triton B as base and ethanol as reaction medium in conjugation with microwave irradiation (Scheme I). Results and Discussion Initial effort was focused on the traditional thermal Suzuki coupling of 2-chloro-5-nitro pyridine with furan-3-boronic acid with five equivalents of triton B as base and ethanol as solvent and 1 mol% of Pd(PPh3)4 as catalyst. It was found that conducting the reaction at 120°C for 12 hr resulted in only little conversion of the starting materials. There is no considerable change in the conversion of starting material even after stretching the reaction temperature to 24 hr. Considering the recent advances of microwave irradiation for rapid reactions, the same reaction was carried out in microwave. Surprisingly, the reaction completed in 10 min with complete conversion of 2-chloro-5-nitro pyridine. This success led to extend this method to a wide range of aryl halides/heteroaryl halides. The microwave reactions were performed in a CEM10 discover model microwave apparatus. In order to check the suitable catalyst for this transformation, Pd(OAc)2, Pd/C and Pd(PPh3)4 were screened and the best result was obtained with Pd(PPh3)4. Further to check the possible effect of ethanol, the reaction was performed with neat triton B and it was observed that the reaction proceeded in relatively less yield (60%). This may be presumed because of less solubility of boronic acid in neat triton.
MESHRAM et al.: TRITON B CATALYZED SUZUKI COUPLING REACTION
1 mol % Pd(PPh3)4 5 eq Triton B
Ar-X
+
Ar1B(OH)2
Ar-Ar1 Ethanol, µW
Ar= aryl, heteroaryl; pyridazyl
Ar1 = aryl, heteroaryl
X= Chloro or Bromo
Scheme I
Having optimized conditions for the rapid palladium catalyzed coupling of aryl/heteroaryl halides with boronic acids, the efficiency of this protocol was explored to a series of 18 aryl/heteroaryl halides and results are summarized in Table I. This general reaction is applicable to a variety of sterically hindered aryl/heteroaryl chlorides, hetero aryl boronic acids. Further the coupling reaction of π-electron deficient halides and boronic acid electron excessive systems were also studied. For example 2-bromo pyridine coupled with thiophene-3-boronic acid (entry 5) which resulted into high yield of expected product. Chloro pyridazinone systems (entries 3 and 4) were also reacted smoothly with ayl/heteroaryl boronic acids. It is worthy to mention that the coupling of sterically hindered aryl chlorides (entries 3 and 4) and aryl bromide (entry 7) with aryl/heteroaryl boronic acids in the same reaction condition furnished high yields of expected products. Thus the present method provides an useful alternative over conventional methods for the same transformation, since our method can avoid the use of strong base and reduce the time severely. In conclusion, a rapid microwave assisted protocol has been developed for Suzuki coupling reaction using triton B as base in ethanol medium. The suggested methodology was applicable to sterically hindered halides as well as to a wide range of aryl halides in particular for aryl chlorides which are usually less reactive. Experimental Section All reactions were carried out without any special precautions in an atmosphere of air. Chemicals were purchased from Aldrich, Fluka and S. D. Fine Chemicals. TLC: precoated silica gel plates (60 F254, 0.2 mm layer; E. Merck). 1H NMR spectra: Varian 200, 400 or Bruker 300 MHz spectrometer; δ in ppm, J in Hz. Mass spectra: VG Autospec; in m/z. Microwave: CEM Discover Benchmate General Procedure Aryl halide (1 mmol), aryl boronic acid (1.2 mmol), triton B (5 mmol), 1 mL of ethanol and
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1 mol% Pd(PPh3)4 were placed in a 10 mL crimpsealed thick walled glass tube equipped with a pressure sensor and magnetic stirrer. The reaction tube was placed inside the cavity of a CEM Discover Benchmate, operated at 120°C (temperature monitored by built-in infrared sensor), power 150 W and pressure 25-30 psi for 10-20 min. After completion of the reaction, the reaction mixture brought to RT, ethanol was evoparated and purified through column. The products (solids) were recrystallized from appropriate solvents. The products were characterized by IR, NMR and mass spectroscopy. The characteristic data of some representative compounds are given below. 2-(Furan-3-yl)-5-nitropyridine (entry 1). Brown solid. m.p. 144-46°C. 1H NMR (CDCl3, 300 MHz): δ 9.38 (d, 1H, J =3.0 Hz), 8.41-8.45 (dd, 1H, J = 9.0 Hz, J = 3.0 Hz), 8.15 (s, 1H), 7.56 (m, 2H), 6.90 (s, 1H); IR (KBr): 3435, 3150, 3091, 1509, 1351, 1162, 767 cm-1; EIMS: m/z 190(M+). Anal. Calcd for C9H6N2O3: C, 56.85; H, 3.18; N, 14.73. Found: C, 56.75; H, 3.27; N, 14.85%. 2-(Furan-3-yl)quinoline-3-carbaldehyde (entry 2). Pale brown crystals. m.p. 102-04°C. 1H NMR (CDCl3, 300 MHz): δ 10.43 (s, 1H), 8,73 (s, 1H), 8.14 (dq, 1H, J = 8.3 Hz, J = 0.5 Hz), 7.96 (d, 1H, J = 7.9 Hz), 7.88-7.89 (m, 1H), 7.83 (ddd, 1H, J = 8.3 Hz, J = 6.7 Hz, J = 1.3 Hz), 7.55-7.62 (m, 2H), 6.96 (m, 1H); IR (KBr): 3126. 2973, 1639, 1630, 1425, 1251, 1168, 866 cm-1; EIMS: m/z 223 (M+). Anal. Calcd for C14H9NO2: C, 75.33; H, 4.06; N, 6.27. Found: C, 75.12; H, 4.1; N, 6.15%. tert-Butyl-4-(5-(furan-3-yl)-1-methyl-6-oxo-1,6dihydropyridazin-4-yl)piperazine-1-carboxylate (entry 3). Yellow solid. m.p. 104-05°C. 1H NMR (CDCl3, 300 MHz): δ 8.37 (d, 1H, J = 1.5 Hz), 7.66 (s, 1H), 7.44-7.45 (dd, 1H, J = 1.5 Hz, J = 0.7 Hz), 7.087.10 (dd, 1H, J = 1.5 Hz, J = 0.7 Hz), 3.80 (s, 3H), 3.5-3.6 (m, 4H), 3.05-3.10 (m, 4H), 1.5 (s, 9H); IR (KBr): 3109, 2882, 1687, 1584, 1158, 721 cm-1; ESIMS: m/z 361 (M++1). Anal. Calcd for C18H24N4O4: C, 59.99; H, 6.71; N, 15.55. Found: C, 60.87; H, 6.62; N, 15.49%. Methyl-4-(5-(4-cyanophenyl)-1-methyl-6-oxo1,6-dihydropyridazin-4-yloxy)benzoate (entry 4). Pale brown solid. m.p. 181-82°C. 1H NMR (CDCl3, 300 MHz): δ 8.05 (d, 2H, J = 9.0 Hz), 7.69 (m, 5H), 7.54 (s, 1H), 7.02 (d, 2H, J = 9.0 Hz), 3.92 (s, 3H), 3.84 (s, 3H); IR (KBr): 3003, 2954, 2218, 1723, 1658, 1245, 763 cm-1; ESIMS: m/z 362 (M++1). Anal. Calcd
INDIAN J. CHEM., SEC B, FEBRUARY 2012
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Table I Suzuki coupling reaction of ayl/hetero aryl halides with aryl/hetero aryl boronic acids Entry
Aryl/heteroaryl halides
Boronic acids
Time (min)
Yield* (%)
B(OH)2 10
OHC
10
92
10
95
10
97
15
98
10
95
B(OH)2
15
93
B(OH)2
15
96
10
94
10
97
Br O
B(OH) 2 11
OHC
Br S
12
OHC
B(OH)2
Br
B(OH)2
O 13
Br O
B(OH) 2
O Br
14
S
15
O
Br
16
O
Br
F
B(OH)2 17
O
Br S
B(OH)2 18
Br S
* Yields after purification
MESHRAM et al.: TRITON B CATALYZED SUZUKI COUPLING REACTION
for C20H15N3O4: C, 66.48; H, 4.18; N, 11.63. Found: C, 66.86; H, 4.26; N, 15.19%. 1-(4-(6-Methoxypyridin-3-yl)phenyl)ethanone (entry 6). Pale yellow solid. m.p. 107-08°C. 1H NMR (CDCl3, 200 MHz): 8.35 (d, 1H, J = 2.9 Hz), 7.95-8.0 (d, 2H, J = 8.7 Hz), 7.72-7.76 (dd, 1H, J = 8.0 Hz, 2.9 Hz); 7.5-7.6 (d, 2H, J = 8.7 Hz), 6.76 (d, 1H, J = 8.0 Hz), 3.95 (s, 3H), 2.6 (s, 3H); IR (KBr): 3067, 2933, 2853, 1671, 1598, 1262, 1014, 826 cm-1; ESIMS: m/z 228(M++1). Anal. Calcd for C14H13NO2: C, 73.99; H, 5.77; N, 6.16. Found: C, 73.91; H, 5.86; N, 6.39%. 3-(Naphthalen-2-yl)furan (entry 7). Brown solid. m.p. 105-06°C. 1H NMR (CDCl3, 200 MHz): δ 7.77.8 (m, 5H), 7.4-7.6 (m, 3H), 7.2 (m, 1H), 6.8 (s, 1H); IR (KBr): 3052, 1513, 1158, 785, 724 cm-1; EIMS: m/z 195 (M++1). Anal. Calcd for C14H10O: C, 86.57; H, 5.19; Found: C, 86.88; H, 5.47%. 5-(Furan-3-yl)-2-hydroxybenzaldehyde (entry 8). Yellow crystals. m.p. 76-7°C. 1H NMR (CDCl3, 200 MHz): δ 10.9 (s, 1Η), 9.9 (s, 1H), 7.62-7.68 (m, 2H), 7.61 (s, 1H), 7.48 (s, 3H), 7.0 (d, 1H, J = 9.3 Hz), 6.62 (s, 1H); IR (KBr): 3134, 3060, 2861, 1665, 1163, 785, 709 cm-1; EIMS: m/z 188(M+). Anal. Calcd for C11H18O3: C, 70.21; H, 4.29; Found: C, 70.05; H, 4.52%. 4-Formylbiphenyl (entry12). Colourless oil. 1H NMR (CDCl3,300 MHz): δ 7.3-7.5 (m, 3H), 7.58 (dt, 2H, J = 6.9 Hz, 1.7 Hz), 7.7 (d, 2H, J = 8.5Hz), 7.92 (d, 2H, J = 8.5 Hz), 10.1 (s, 1H); IR (KBr): 3029, 2925, 2855, 2731, 1697, 1601, 1107, 967, 758 cm-1; EIMS: m/z 182 (M+). Anal. Calcd for C13H10O: C, 85.69; H, 5.53; Found: C, 85.49; H, 5.52%. 4-Fluoro-4'-methoxybiphenyl (entry 15). White solid; m.p. 88-89°C. 1H NMR (CDCl3, 200 MHz): δ 3.85 (s, 3H), 6.95-6.99 (m, 2H), 7.08-7.12 (m, 2H), 7.45-7.51 (m, 4H); IR (KBr): 3030, 1610, 1495, 1240, 1040, 828, 810 cm-1; EIMS: m/z 200(M+). Anal. Calcd for C13H11FO: C, 77.21; H, 5.40. Found: C, 77.41; H, 5.62%. 4-Methoxybiphenyl (entry 16). White solid. m.p. 85-87°C. 1H NMR (CDCl3, 200 MHz): δ 3.85 (s, 3H), 6.95 (d, 2H, J = 6.8 Hz), 7.30-7.32 (m, 1H), 7.40-7.43 (m, 2H), 7.51-7.55 (m, 4H); IR (KBr): 3031, 3000, 2960, 2935, 2834, 1288, 1270, 1249, 833, 688 cm-1; EIMS: m/z 184 (M+). Anal. Calcd for C13H12O: C, 84.75; H, 6.57. Found: C, 84.45; H, 6.69%. 3-(4-Methoxyphenyl)thiophene (entry 17). White solid. m.p. 130-31°C. 1H NMR (CDCl3, 400 MHz):
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δ 3.83 (s, 3H), 6.9 (d, 2H, J = 6.5 Hz), 7.3-7.34 (m, 3H), 7.5 (d, 2H, J = 6.5 Hz); IR (KBr): 3100, 1240, 835, 780, 730 cm-1; EIMS: m/z 190 (M+). Anal. Calcd for C11H10OS: C, 69.44; H, 5.30. Found: C, 69.90; H, 5.70%. 3-Phenylthiophene (entry 18). Pale yellow solid. m.p. 89-98°C. 1H NMR (CDCl3, 400 MHz): δ 7.58 (d, 2H, J = 7.3 Hz) 7.43 (m, 1H), 7.38-7.40 (m, 4H), 7.27 (m, 1H); IR (KBr): 3116, 3087, 3065, 3036, 1603, 1578, 1489, 969 cm-1; EIMS: m/z 160(M+). Anal. Calcd for C10H8S: C, 74.96; H, 5.03. Found: C, 74.90; H, 5.60%. Acknowledgements The authors BRVP, DAK and BCKR thank CSIR and UGC New Delhi for the award of fellowships. References 1 (a) Miyaura N & Suzuki A, Chem Rev, 95, 1995, 2457; (b) Hassan J, Sevignon M, Gozzi C, Schulz E & Lemaire M, Chem Rev, 102, 2002, 1359; (c) Suzuki A, J Organomet Chem, 576, 1999, 147; (d) Wolfe J P, Singer R A, Yang B H & Buchwald S L, J Am Chem Soc, 121, 1999, 9550; (e) Farina V, Adv Synth Catal, 346, 2004, 1553; (f) Littke A F & Fu G C, Angew Chem, 114, 2002, 4350. 2 (a) Saito B & Fu G C, J Am Chem Soc, 129, 2007, 9602; (b) Kondolff I, Doucet H & Santelli M, Tetrahedron, 60, 2004, 3813. 3 Hoshi T, Nakazawa T, Saitoh I, Mori A, Suzuki T, Sakai J & Hagiwara H, Org Lett, 10, 2008, 2063. 4 Fleckenstein C A & Plenio H, J Org Chem, 73, 2008, 3236. 5 Anderson J C, Namli H & Roberts C A, Tetrahedron, 53, 1997, 15134. 6 Palackova V, Hutka M & Toma S, Ultrasonics Sonochemistry, 2005, 99. 7 (a) Meshram H M, Reddy B Ch K & Goud P R, Synth Commun, 39, 2009, 2297; (b) Meshram H M, Eeshwaraia B, Sreenivas M, Aravind D, Syama Sundar B & Yadav J S, Synth Commun, 39, 2009, 1857; (c) Mayer S, Merour J Y, Joseph B & Guillaumet G, Eur J Org Chem, 2002, 1646; (d) Anklam E & Margaretha P, Helv Chim Acta, 67, 1984, 2206; (e) Bulbule V J, Jnaneshwara G K, Deshmukh R R, Borate H B & Deshpande V H, Synth Commun, 31, 2001, 3623. 8 (a) Appukkuttan P & Eycken E V D, Eur J Org Chem, 2008, 1133; (b) Kappe C O, Angew Chem Int Ed, 43, 2004, 6250. 9 (a) Meshram H M, Prasad B R V & Kumar D A, Tetrahedron Lett, 51, 2010, 3477; (b) Meshram H M, Kumar G S P, Ramesh P & Reddy B C K, Tetrahedron Lett, 51, 2010, 2580; (c) Meshram H M, Kumar D A & Reddy B Ch K, Helv Chim Acta, 92, 2009, 1002; (d) Meshram H M, Kumar D A & Prasad B R V, Synth Commun, 29, 2009, 2317; (e) Meshram H M, Kumar D A, Prasad B R V & Goud P R, Helv Chim Acta, 93, 2010, 648. 10 CEM Corporation, PO Box 200, Matthews, NC 28106.
