English

• 1.   Introduction

  Pyridines are important fundamental heterocycles which are found in numerous natural products, functional materials, agrochemicals and pharmaceutical drugs.^[1] Molecules bearing a pyridine moiety exhibit a wide range of biological activities, such as anxiolytic, ^[2] antidiabetic, ^[3] antiviral, ^[4] antibacterial, ^[5] antileishmanial, ^[6] anti-inflammatory, ^[7] and anti-chagasic activities.^[8] In addition, pyridine dervatives are extensively used as various valuable ligands (such as bipyridine and terpyridine), organic bases and catalysts.^[9] As a result, the synthesis of pyridine and its derivatives has attracted the attention of members of the scientific community for more than 140 years.^[10]

  In recent years, metalloporphyrins have been used as cytochrome P-450 models and have been found to be highly efficient homogeneous or heterogeneous catalysts for the oxidation reactions of organic compounds.^[11] Metalloporphyrin-mediated hydrocarbon functionalization is of particular importance in biomimetic investigation and is potentially useful in organic synthesis. The epoxidation, aziridination, and cyclopropanation of alkenes and the hydroxylation and amidation of saturated C—H bonds are among the most common hydrocarbon-functionalization reactions mediated by a metalloporphyrin, which are widely believed to proceed by oxygen-, nitrogen-, and carbon-atom^[12] transfer from oxo-, imido-, and carbene- metalloporphyrin active species, respectively.^[13] In this field, our group has reported some work about metalloporphyrins catalyzed hydrocarbons convert into value- added functional molecules through C—O, C—N and C—C bond formation^[14]. As a part of our continuous efforts for metalloporphyrin-based atom/group transfer catalysis, herein, we report the first examples of the iron(Ⅲ)-por- phyrin-catalyzed cyclization of ketones with dimethyl sulfoxide (DMSO) and ammonium acetate for the synthesis of unsymmetrical and symmetrical pyridines by employing DMSO as C₄ or C₆ source, respectively.^[15] This method uses non-noble metals and proceeds under mild reaction conditions with operational simplicity, which thus allows the expedient and atom-economical assembly of pyridines from readily available ketones.

  2.   Results and discussion

  We first surveyed the catalytic cyclization of ketones by various metalloporphyrins with different nitrogen sources. To our delight, acetophenone (1a) could be converted into pyridine (2a) in 72% yield with 3.0 equiv. of NH₄OAc and 1.0 mol% T(p-OMe)PPFeCl in DMSO under 101 kPa O₂ at 120 ℃. The results in Table 1 showed that other iron(Ⅲ)-porphyrin catalysts, including T(p-Cl)PPFeCl, T(p-Me)PPFeCl and TPPFeCl could also afford the product, but with less efficiency (Table 1, Entries 1~4). On the other hand, other metal complexes of T(p-MeO)PP such as T(p-MeO)PPCu, T(p-MOe)PPCo, T(p-MeO)PPMnCl and T(p-MeO)PPNi were also tested, and the results demon-strated that T(p-MeO)PPFeCl was the best choice (Table 1, Entries 5~8). When other nitrogen sources were used instead of NH₄OAc, none showed higher efficiency than NH₄OAc (Table 1, Entries 9~13). Decreased yield was observed when a lower or higher catalyst loading was applied (Table 1, Entries 14, 15).

  Table 1

  

  Table 1.  Optimization of reaction conditions

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  Entry	N source	Catalyst	Temp./℃	Yieldb/%
  1	NH4OAc	T(p-MeO)PPFeCl	120	72
  2	NH4OAc	T(p-Cl)PPFeCl	120	65
  3	NH4OAc	T(p-Me)PPFeCl	120	67
  4	NH4OAc	TPPFeCl	120	62
  5	NH4OAc	—	120	12
  6	NH4OAc	T(p-MeO)PPCu	120	51
  7	NH4OAc	T(p-MeO)PPCo	120	38
  8	NH4OAc	T(p-MeO)PPMnCl	120	42
  9	NH4OAc	T(p-MeO)PPNi	120	26
  10	(NH4)2CO3	T(p-MeO)PPFeCl	120	42
  11	NH4HCO3	T(p-MeO)PPFeCl	120	40
  12	NH3•H2O	T(p-MeO)PPFeCl	120	36
  13	NH4I	T(p-MeO)PPFeCl	120	18
  14	HCOONH4	T(p-MeO)PPFeCl	120	65
  15	NH4OAc	T(p-MeO)PPFeCl	100	47
  16	NH4OAc	T(p-MeO)PPFeCl	130	70
  17c	NH4OAc	T(p-MeO)PPFeCl	120	63
  18d	NH4OAc	T(p-MeO)PPFeCl	120	69
  a Reaction conditions: acetophenone (1a, 0.5 mmol), N source (1.5 mmol), catalyst (1.0 mol%) and solvent (2 mL) for 24 h under O2 atmosphere at 120 ℃. b Isolated yield. c T(p-MeO)PPFeCl (0.5 mol%). d T(p-MeO)PPFeCl (2.0 mol%).

  Subsequently, the scope of the (hetero)aryl methyl ketones was investigated under the standard reaction conditions (Table 2). The results revealed that aryl methyl ketones bearing a variety of functional groups and substitution patterns afforded the desired products in moderate to good yields (34%~82%). As shown in Table 1, acetophenone derivatives bearing electrondonating substituents (MeO, EtO, Me) could achieve this conversion in 42%~82% yields (Table 2, Entries 1~8). Nevertheless, the acetophenone derivatives with electron-withdrawing substituents (F, Cl, Br, I, NO₂, CN, CF₃) could be converted into pyridines in yields ranging from 34% to 70% (Table 2, Entries 9~17). Furthermore, acetophenone bearing the same substituents at different positions had influence on the efficiency of this transformation. For example, 2- methylacetophenone gave lower yield than 4-/3- methylacetophenone (Table 2, Entries 4~6). Importantly, halogen substituents on the phenyl ring were well tolerated with this conversion, which enable a potential application in further functionalization (Table 2, Entries 9~14). Furthermore, 2-acetonaphthone and 2-acetylthiophene could also provide the desired product in moderate yield (Table 2, Eentries 18 and 19).

  Table 2

  

  Table 2.  Scope of acetophenones

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  Entry	(Het)Ar	2	Yield/%
  1	Ph	2a	72
  2	4-MeOC6H4	2b	81
  3	4-EtOC6H4	2c	85
  4	4-MeC6H4	2d	78
  5	3-MeC6H4	2e	73
  6	2-MeC6H4	2f	42
  7	3, 4-(MeO)2C6H3	2g	82
  8	2, 4-(MeO)2C6H3	2h	71
  9	4-FC6H4	2i	58
  10	4-ClC6H4	2j	70
  11	4-BrC6H4	2k	66
  12	3-BrC6H4	2l	54
  13	2-BrC6H4	2m	34
  14	4-IC6H4	2n	54
  15	3-NO2C6H4	2o	35
  16	4-CNC6H4	2p	66
  17	4-CF3C6H4	2q	58
  18	2-Naphthyl	2r	68
  19	Furyl	2s	52
  a Standard conditions: ketones (0.5 mmol), NH4OAc (3.0 equiv.), T(p-MeO)- PPFeCl (1.0 mol%), DMSO (2.0 mL), 120 ℃ for 24 h. b Isolated yield.

  It is worth noting that the substrates of 1f, 1m and 1o could also gave the corresponding products, but the yields are only 42%, 34% and 35%, respectively. With further research, we found that the symmetrical pyridines were obtained and the results are in contrary to the previous literature which only unsymmetrical pyridines were obtained (Table 3).^[15b]

  Table 3

  

  Table 3.  Scope of acetophenones

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  Entry	Ar	1	Yield/%
  			2a	2'b
  1	2-CH3C6H4	1f	42 (2f)	40 (2f')
  2	2-BrC6H4	1m	34 (2m)	38 (2m')
  3	3-NO2C6H4	1o	35 (2o)	30 (2o')
  a Standard conditions: ketones (0.5 mmol), NH4OAc (3.0 equiv.), T(p-MeO)- PPFeCl (1.0 mol%), DMSO (2.0 mL), 120 ℃ for 24 h. b Isolated yield.

  To expand the substrate scope of this transformation, α-substituent on the ketones was investigated and the results are displayed in Table 4. Surprisingly, the substitution patterns of the pyridine ring changed when propiophenone was used as a substrate instead of an aryl methyl ketone. Based on this result, we proceeded to investigate a variety of other propiophenone compounds. As expected, the electronic natue of the phenyl ring on the propiophenone compound had little impact on the efficiency of the reaction (54%~71% yields for 1t~1w). Moreover, the use of valerophenone, 1, 3-diphenylpropane-1, 3-dione or benzocyclohexanone as a substrate under the optimized conditions also gave the corresponding products 3e, 3f and 3g in moderate to good yields (54%~65%).

  Table 4

  

  Table 4.  Scope of α-substituent ketones

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  Entry	R1	R2	1	3	Yieldb/%
  1	Ph	Me	1t	3a	65
  2	4-MeOC6H4	Me	1u	3b	71
  3	4-MeC6H4	Me	1v	3c	68
  4	4-ClC6H4	Me	1w	3d	60
  5	Ph	n-Pr	1x	3e	54
  6	Ph	PhC＝O	1y	3f	65
  7	CH2＝CHC6H4	H	1z		0
  8	Ph	Ph	1af		0
  9			1ag	3g	64
  10			1ah		0
  a Standard conditions: ketones (0.5 mmol), NH4OAc (3.0 equiv.), T(p-OMe)- PPFeCl (1.0 mol%), DMSO (2.0 mL), 120 ℃ for 24 h. b Isolated yield.

  In order to have a deeper understanding on the mechanism, several control experiments were conducted (Scheme 1). The reaction of hydrated hemiacetal (1ab) or 1-phenyl- 2-propen-1-one (1ac) with ammonium acetate under the standard conditions, did not lead to the desired product 2a (Scheme 1), which suggested that these two substrates were not intermediates in the reaction. To lend further support to this mechanism, we investigated the preparation and subsequent reaction of substrates 1ad and 1ae. The results revealed that 1ad and 1ae could be converted to the desired products, albeit in a lower yield (Scheme 1), which clearly confirmed that 1ad and 1ae were not the key intermediates in the transformation. The use of DMSO-d₆ in the reaction showed that DMSO behaved as a source of methylene units, following the isolation of the partially deuterated products 2a-d₁ and 3a-d₁ (Scheme 1), which further confirmed that DMSO was a source of methylene units.

  Scheme 1

  

  Scheme 1.  Control experiments

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  On the basis of the experimental results described above and previous literatures, ^{[15, 16]} we propose a possible mechanism for this transformation (Figure 1). The initial reaction of carbonyl group of ketones (1a) with ammonia from ammonium acetate would give intermediate A. Contrary to the previous literature of two mechanisms to obtain unsymmetrical or symmetrical product, ^[23] the intermediate A would undergo two pathway to give unsymmetrical or symmetrical pyridines respectively. DMSO could be protonated by acetic acid which was formed in-situ from ammonium acetate to give an activated species, which would be converted to the methylene source B. When the substrates were methyl ketones, the subsequent nucleophilic attack of B by the nitrogen atom of A would lead to the formation of intermediate C. Intermediate C would then undergo a rapid nucleophilic attack on acetophenone and through a dehydration reaction to afford D. The elimination of methanethiol, followed by sequential 6p electrocyclization and aromatization^[14] reactions to provide the desired product 2a. On the other hand, when the substrates were α-substituent ketones, the subsequent nucleophilic attack of B by the α-carbon atom of A would lead to the formation of intermediate E. Intermediate E would then undergo a rapid nucleophilic attack on α-substituent ketones and through a dehydration reaction to afford F. Fi- nally, annulation and aromatization of F would then give the desired product 3a.

  Figure 1

  

  Figure 1.  Possible mechanism

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  3.   Conclusions

  In summary, we have developed a novel and efficient methodology for the synthesis of diverse and functionalized pyridines in good yield by iron(Ⅲ)-porphyrin-catalyzed three-component reactions of readily available ketones with DMSO and ammonium acetate. The methodology provides an environmentally friendly, simple and regioselective access to a variety of multisubstituted pyridines. This protocol tolerates a wide range of substituents, heteroatoms, and steric environments to provide polysubstituted pyridine derivatives and forms various C—C and C—N bonds in a single procedure.

  4.   Experimental section

  4.1   General methods

  Materials obtained from commercial suppliers were used as received unless mentioned otherwise. Products were purified by flash chromatography on silica gel (300~400 mesh), and were characterized by ¹H NMR, and ¹³C NMR. ¹H NMR spectra were recorded on 400 MHz NMR spectrometer. ¹³C NMR spectra were obtained at 100 MHz and referenced to the internal solvent signals (central peak is δ 77.0 in CDCl₃). High-resolution mass spectra (HRMS) were measured on an electrospray ionization (ESI) apparatus using time-of-flight (ToF) mass spectrometry.

  4.2   Typical experimental procedure for the formation of pyridines from arylketones

  In a Schlenk tube of 25 mL, CH₃COONH₄ (1.5 mmol, 3.0 equiv.), acetophenone 1 (0.5 mmol, 1.0 equiv.) and T(p-OMe)PPFeCl (1.0 mmol%) were dissolved in DMSO (2 mL) and stirred at 120 ℃ for 24 h. After completion of the reaction. The resulting solution was cooled to room temperature. The solution was diluted with ethyl acetate (10 mL), washed with water (5 mL), extracted with ethyl acetate (5 mL×3), and dried over anhydrous Na₂SO₄ and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel to give the desired product.

  2, 4-Diphenylpyridine (2a): Yellow solid, 42 mg, 72% yield. m.p. 54~58 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.74 (d, J＝5.1 Hz, 1H), 8.05 (d, J＝7.7 Hz, 2H), 7.92 (s, 1H), 7.69 (d, J＝7.6 Hz, 2H), 7.55~7.40 (m, 7H); ¹³C NMR (CDCl₃, 100 MHz) δ: 158.1, 150.1, 150.0, 149.4, 139.5, 138.6, 129.2, 129.1, 128.8, 127.1, 127.0, 120.3, 118.8; IR (KBr) ν: 1605, 1593, 1578, 1540, 1467, 1387, 774, 728, 694, 610 cm^－1; HRMS (EI) calcd for C₁₇H₁₄N: 232.1125, found 232.1123.

  2, 4-Bis(4-methoxyphenyl)pyridine (2b): White solid, 59 mg, 81% yield. m.p. 131~134 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.69 (d, J＝5.0 Hz, 1H), 7.94 (d, J＝7.6 Hz, 2H), 7.89 (s, 1H), 7.59 (d, J＝7.6 Hz, 2H), 7.40 (d, J＝5.0 Hz, 1H), 7.30 (d, J＝7.7 Hz, 4H), 2.42 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 158.0, 149.9, 149.7, 149.2, 139.2, 139.1, 136.7, 135.7, 129.9, 129.5, 126.9, 119.8, 118.3, 21.3, 21.2; IR (KBr) ν: 1607, 1595, 1514, 1469, 1251, 1238, 1183, 1043, 1019, 827, 815 cm^－1; HRMS (EI) calcd for C₁₉H₁₈NO₂ 292.1332, found 292.1331.

  2, 4-Bis(4-ethoxyphenyl)pyridine (2c): White solid, 68 mg, 85% yield. m.p. 135~138 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.58 (d, J＝4.9 Hz, 1H), 7.90 (d, J＝8.3 Hz, 2H), 7.75 (s, 1H), 7.55 (d, J＝8.3 Hz, 2H), 7.28 (d, J＝4.9 Hz, 1H), 6.92 (d, J＝8.3 Hz, 4H), 4.02 (q, J＝6.8 Hz, 4H), 1.37 (t, J＝6.4 Hz, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 159.9, 157.6, 149.7, 148.9, 131.9, 130.6, 128.4, 128.2, 119.1, 117.6, 115.1, 114.7, 114.0, 63.7, 63.6, 14.9, 14.8; IR (KBr) ν: 2978, 1601, 1541, 1513, 1465, 1396, 1254, 1239, 1181, 1116, 1048, 828, 809 cm^－1; HRMS (EI) calcd for C₂₁H₂₂NO₂ 320.1645, found 320.1647.

  2, 4-Di-p-tolylpyridine (2d): White solid, 51 mg, 78% yield. m.p. 104~106 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.69 (d, J＝5.0 Hz, 1H), 7.94 (d, J＝7.6 Hz, 2H), 7.89 (s, 1H), 7.59 (d, J＝7.6 Hz, 2H), 7.40 (d, J＝5.0 Hz, 1H), 7.30 (d, J＝7.7 Hz, 4H), 2.42 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 158.0, 149.9, 149.2, 139.2, 139.1, 136.7, 135.7, 129.9, 129.5, 126.9, 119.8, 118.3, 21.3, 21.2; IR (KBr) ν: 1596, 1539, 1515, 1470, 1382, 808, 747, 527, 436 cm^－1; HRMS (EI) calcd for C₁₉H₁₈N 260.1434, found 260.1436.

  2, 4-Di-m-tolylpyridine (2e): Yellow oil, 47 mg, 73% yield. ¹H NMR (CDCl₃, 400 MHz) δ: 8.71 (d, J＝5.1 Hz, 1H), 7.90 (d, J＝6.9 Hz, 2H), 7.82 (d, J＝7.7 Hz, 1H), 7.49 (d, J＝7.0 Hz, 2H), 7.43~7.36 (m, 3H), 7.26 (t, J＝6.7 Hz, 2H), 2.45 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 158.2, 149.9, 149.6, 139.4, 138.8, 138.6, 138.5, 129.9, 129.8, 129.1, 128.7, 127.9, 127.8, 124.2, 124.1, 120.3, 118.9, 21.6, 21.5; IR (KBr) ν: 1594, 1531, 1508, 1462, 1372, 784, 707 cm^－1; HRMS (EI) calcd for C₁₉H₁₈N 260.1434, found 260.1435.

  2, 4-Di-o-tolylpyridine (2f): Yellow oil, 27 mg, 42% yield. ¹H NMR (CDCl₃, 400 MHz) δ: 8.77 (d, J＝5.0 Hz, 1H), 7.45 (d, J＝7.0 Hz, 1H), 7.39 (d, J＝4.5 Hz, 1H), 7.30 (t, J＝5.4 Hz, 5H), 7.26 (d, J＝9.2 Hz, 3H), 2.41 (d, J＝6.3 Hz, 3H), 2.34 (s, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 159.6, 150.3, 148.8, 140.1, 139.1, 135.8, 135.1, 130.8, 130.7, 129.8, 129.4, 128.5, 128.4, 126.2, 126.0, 124.8, 122.4, 20.5, 20.4; IR (KBr) ν: 1594, 1541, 1456, 1386, 751, 727 cm^–1; HRMS (EI) calcd for C₁₉H₁₈N 260.1434, found 260.1438.

  2, 6-Di-o-tolylpyridine (2f'): Yellow oil, 26 mg, 40% yield. ¹H NMR (CDCl₃, 400 MHz) δ: 7.73 (d, J＝7.7 Hz, 1H), 7.38 (d, J＝8.9 Hz, 2H), 7.29 (d, J＝7.7 Hz, 2H), 7.22~7.16 (m, 6H), 2.35 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 159.5, 140.6, 136.4, 135.9, 130.7, 129.9, 128.3, 125.9, 122.1, 20.6; IR (KBr) ν: 1601, 1562, 1457, 1374, 767 cm^－1; HRMS (EI) calcd for C₁₉H₁₈N 260.1434, found 260.1435.

  2, 4-Bis(3, 4-dimethoxyphenyl)pyridine (2g): Yellow solid, 72 mg, 82% yield. m.p. 111~113 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.67 (d, J＝5.0 Hz, 1H), 7.84 (s, 1H), 7.71 (s, 1H), 7.56 (d, J＝8.3 Hz, 1H), 7.38 (d, J＝5.0 Hz, 1H), 7.28 (d, J＝8.1 Hz, 1H), 7.19 (s, 1H), 6.99 (t, J＝7.8 Hz, 2H), 4.02 (s, 3H), 3.98 (s, 3H), 3.95 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 157.6, 150.0, 150.1, 149.7, 149.5, 149.3, 149.2, 132.4, 131.3, 119.8, 119.5, 117.9, 111.6, 111.1, 110.2, 110.1, 56.2, 56.1, 56.0, 56.0; IR (KBr) ν: 1597, 1543, 1466, 1385, 1237, 1110, 1057, 982, 943, 815 cm^－1; HRMS (EI) calcd for C₂₁H₂₂NO₄ 352.1543, found 352.1548.

  2, 4-bis(2, 4-dimethoxyphenyl)pyridine (2h): Yellow solid, 62 mg, 71% yield. m.p. 115~118 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.65 (d, J＝5.1 Hz, 1H), 7.90 (s, 1H), 7.74 (d, J＝8.5 Hz, 1H), 7.35 (dd, J＝14.4, 6.7 Hz, 2H), 6.60 (dd, J＝21.2, 6.4 Hz, 4H), 3.85 (s, 6H), 3.83 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 161.4, 161.3, 158.1, 157.9, 155.5, 148.5, 146.1, 132.1, 131.3, 125.3, 122.3, 122.0, 121.0, 105.0, 99.1, 98.9, 55.7, 55.6, 55.5, 55.4; IR (KBr) ν: 1592, 1536, 1451, 1391, 1232, 1121, 1050, 976, 938, 810 cm^－1; HRMS (EI) calcd for C₂₁H₂₂NO₄ 352.1543, found 352.1547.

  2, 4-Bis(4-fluorophenyl)pyridine (2i): White solid, 39 mg, 58% yield, m.p. 78~81 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.62 (d, J＝5.1 Hz, 1H), 7.95 (dd, J＝8.0, 5.7 Hz, 2H), 7.74 (s, 1H), 7.57 (dd, J＝7.9, 5.6 Hz, 2H), 7.31 (d, J＝5.1 Hz, 1H), 7.10 (q, J＝8.7 Hz, 4H); ¹³C NMR (CDCl₃, 100 MHz) δ: 164.8 (d, J＝13.5 Hz), 162.3 (d, J＝14.2 Hz), 157.1, 150.1, 148.5, 135.4 (d, J＝3.0 Hz), 134.5 (d, J＝3.1 Hz), 128.9, 128.8, 120.0, 118.3, 116.2 (d, J＝21.7 Hz), 115.7 (d, J＝21.6 Hz); IR (KBr) ν: 1609, 1514, 1473, 1224, 1157, 816, 556 cm^－1; HRMS (EI) calcd for C₁₇H₁₂F₂N 268.0932, found 268.0936.

  2, 4-Bis(4-chlorophenyl)pyridine (2j): White solid, 52 mg, 70% yield. m.p. 101~104 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.72 (d, J＝5.1 Hz, 1H), 7.98 (d, J＝8.1 Hz, 2H), 7.84 (s, 1H), 7.61 (d, J＝8.0 Hz, 2H), 7.47 (t, J＝7.9 Hz, 4H), 7.41 (d, J＝5.0 Hz, 1H); ¹³C NMR (CDCl₃, 100 MHz) δ: 157.0, 150.3, 148.3, 137.6, 136.8, 135.5, 135.4, 129.4, 129.0, 128.4, 128.3, 120.3, 118.3; IR (KBr) ν: 1598, 1542, 1495, 1463, 1417, 1376, 1090, 1011, 816, 753 cm^－1; HRMS (EI) calcd for C₁₇H₁₂Cl₂N 300.0341, found 300.0343.

  2, 4-Bis(4-bromophenyl)pyridine (2k): White solid, 64 mg, 66% yield. m.p. 137~139 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.72 (d, J＝5.0 Hz, 1H), 7.92 (d, J＝8.3 Hz, 2H), 7.84 (s, 1H), 7.63 (t, J＝8.4 Hz, 4H), 7.54 (d, J＝8.2 Hz, 2H), 7.43~7.39 (m, 1H); ¹³C NMR (CDCl₃, 100 MHz) δ: 157.0, 150.3, 148.4, 138.1, 137.2, 132.4, 132.0, 128.7, 128.6, 123.8, 123.7, 120.3, 118.2; IR (KBr) ν: 1593, 1537, 1375, 1071, 1006, 812 cm^－1; HRMS (EI) calcd for C₁₇H₁₂Br₂N 387.9331, found 387.9334.

  2, 4-Bis(3-bromophenyl)pyridine (2l): White solid, 53 mg, 54% yield. m.p. 94~96 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.73 (t, J＝7.9 Hz, 1H), 8.21 (s, 1H), 7.97 (d, J＝7.8 Hz, 1H), 7.82 (d, J＝9.1 Hz, 2H), 7.64~7.53 (m, 3H), 7.39 (dt, J＝15.4, 6.3 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 156.64, 150.32, 148.10, 141.16, 140.37, 132.16, 130.72, 130.35, 130.17, 130.15, 125.77, 125.60, 123.33, 123.14, 120.71, 118.67; IR (KBr) ν: 1591, 1542, 1462, 783, 706 cm^－1; HRMS (EI) calcd for C₁₇H₁₂Br₂N 387.9331, found 387.9335.

  2, 4-Bis(2-bromophenyl)pyridine (2m): White solid, 33 mg, 34% yield. m.p. 124~126 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.81 (d, J＝5.1 Hz, 1H), 7.72~7.67 (m, 3H), 7.62 (d, J＝7.8 Hz, 1H), 7.45~7.37 (m, 4H), 7.29~7.23 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz) δ: 158.0, 148.9, 140.7, 139.8, 133.5, 133.4, 132.3, 131.6, 130.9, 130.0, 129.9, 127.8, 127.6, 125.6, 123.2, 121.9, 121.8; IR (KBr) ν: 1601, 1564, 1542, 1458, 1432, 1387, 1076, 1023, 899, 755 cm^－1; HRMS (EI) calcd for C₁₇H₁₂Br₂N 387.9331, found 387.9336.

  2, 6-Bis(2-bromophenyl)pyridine (2m'): Yellow oil, 37 mg, 38% yield. ¹H NMR (CDCl₃, 400 MHz) δ: 7.84 (t, J＝7.8 Hz, 1H), 7.70~7.58 (m, 6H), 7.40 (t, J＝7.5 Hz, 2H), 7.24 (t, J＝7.7 Hz, 2H); ¹³C NMR (CDCl₃, 100 MHz) δ: 157.9, 141.2, 135.9, 133.3, 131.8, 129.8, 127.6, 123.4, 121.9; IR (KBr) ν: 1637, 1384, 1184, 1126, 800, 688, 618 cm^–1; HRMS (EI) calcd for C₁₇H₁₂Br₂N 387.9331, found 387.9333.

  2, 4-Bis(4-iodophenyl)pyridine (2n): White solid, 65mg, 54% yield. m.p. 171~173 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.71 (d, J＝4.7 Hz, 1H), 7.91 (d, J＝8.3 Hz, 2H), 7.83 (s, 1H), 7.62 (t, J＝8.1 Hz, 4H), 7.53 (d, J＝8.3 Hz, 2H), 7.40 (d, J＝3.6 Hz, 1H); ¹³C NMR (CDCl₃, 100 MHz) δ: 157.01, 150.29, 148.36, 138.05, 137.21, 132.39, 131.98, 128.65, 128.60, 123.75, 123.72, 120.28, 118.17; IR (KBr) ν: 1596, 1539, 1372, 1001, 809 cm^－1; HRMS (EI): calculated for C₁₇H₁₂I₂N 483.9054, found 483.9058.

  2, 4-Bis(3-nitrophenyl)pyridine (2o): White solid, 28 mg, 35% yield. m.p. 194~197 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.94 (s, 1H), 8.87 (d, J＝5.0 Hz, 1H), 8.57 (s, 1H), 8.46 (d, J＝7.8 Hz, 1H), 8.36 (d, J＝8.2 Hz, 1H), 8.32 (d, J＝8.1 Hz, 1H), 8.10~8.02 (m, 2H), 7.80~7.68 (m, 2H), 7.59 (d, J＝4.8 Hz, 1H); ¹³C NMR (CDCl₃, 100 MHz) δ: 155.9, 150.8, 148.9, 148.9, 147.5, 140.5, 139.8, 133.1, 132.9, 130.4, 129.9, 124.1, 124.0, 122.1, 122.0, 121.3, 118.7; IR (KBr) ν: 1632, 1599, 1530, 1353, 815, 730, 677 cm^－1; HRMS (EI) calcd for C₁₇H₁₂N₃O₄ 322.0822, found 322.0825.

  2, 6-Bis(3-nitrophenyl)pyridine (2o'): White solid, 24mg, 30% yield. m.p. 162~165 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.96 (s, 2H), 8.55 (d, J＝8.8 Hz, 2H), 8.32 (d, J＝8.0 Hz, 2H), 7.99 (d, J＝7.8 Hz, 1H), 7.89~7.83 (m, 2H), 7.72 (t, J＝8.0 Hz, 2H); ¹³C NMR (CDCl₃, 100 MHz) δ: 154.8, 148.9, 140.6, 138.5, 132.9, 130.0, 124.0, 121.8, 120.0; IR (KBr) ν: 1608, 1572, 1517, 1457, 1374, 1332, 786, 692 cm^－1; HRMS (EI) calcd for C₁₇H₁₂N₃O₄ 322.0822, found 322.0824.

  4, 4'-(Pyridine-2, 4-diyl)dibenzonitrile (2p): White solid, 46 mg, 66% yield, m.p. 175~178 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.85 (d, J＝4.7 Hz, 1H), 8.19 (d, J＝8.1 Hz, 2H), 7.94 (d, J＝6.2 Hz, 1H), 7.81 (t, J＝7.1 Hz, 6H), 7.53 (d, J＝4.5 Hz, 1H); ¹³C NMR (CDCl₃, 100 MHz) δ: 156.26, 150.80, 147.86, 142.98, 142.49, 133.04, 132.69, 132.63, 127.91, 127.65, 127.53, 121.36, 119.11, 113.16, 112.92; IR (KBr) ν: 2226, 1587, 1539, 1489, 1471, 1423, 1368, 1084, 818 cm^－1; HRMS (EI) calcd for C₁₇H₁₂N₃ 282.1086, found 282.1087.

  2, 4-Bis(4-(trifluoromethyl)phenyl)pyridine (2q): White solid, 53 mg, 58% yield, m.p. 69~70 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.81 (d, J＝5.0 Hz, 1H), 8.17 (d, J＝8.1 Hz, 2H), 7.95 (s, 1H), 7.80~7.75 (m, 6H), 7.51 (d, J＝5.0 Hz, 1H); ¹³C NMR (CDCl₃, 100 MHz) δ: 156.8, 150.5, 148.3, 142.3, 141.8, 138.0, 131.4 (d, J＝15.3 Hz), 131.1 (d, J＝15.1 Hz), 127.6, 127.4, 126.2 (q, J＝3.7 Hz), 125.8 (q, J＝3.8 Hz), 121.1, 119.8, 119.1; IR (KBr) ν: 1629, 1551, 1492, 1471, 1425, 1382, 1324, 1176, 830 cm^－1; HRMS (EI) calcd for C₁₉H₁₂F₆N 368.0868, found 368.0869.

  2, 4-Di(naphthalen-2-yl)pyridine (2r): Yellow solid, 56 mg, 68% yield, m.p. 110~113 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.81 (d, J＝5.0 Hz, 1H), 8.57 (s, 1H), 8.22 (d, J＝8.6 Hz, 1H), 8.17 (s, 2H), 7.95 (t, J＝9.1 Hz, 4H), 7.90~7.84 (m, 2H), 7.80 (d, J＝8.5 Hz, 1H), 7.57~7.48 (m, 5H); ¹³C NMR (CDCl₃, 100 MHz) δ: 157.9, 150.1, 149.5, 136.6, 135.7, 133.8, 133.6, 133.5, 129.0, 128.8, 128.6, 128.5, 127.8, 127.7, 126.9, 126.8, 126.7, 126.6, 126.6, 126.4, 124.7, 124.7, 120.6, 119.3; IR (KBr) ν: 1632, 1590, 1547, 828, 812, 756, 480 cm^－1; HRMS (EI) calcd for C₂₅H₁₈N 332.1434, found 332.1436.

  2, 4-Di(thiophen-2-yl)pyridine (2s): Yellow solid, 32 mg, 52% yield. m.p. 55~58 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.54 (d, J＝5.2 Hz, 1H), 7.83 (s, 1H), 7.68 (d, J＝3.2 Hz, 1H), 7.55 (t, J＝5.0 Hz, 1H), 7.44 (dd, J＝12.1, 6.2 Hz, 2H), 7.35 (d, J＝5.1 Hz, 1H), 7.19~7.12 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz) δ: 153.1, 145.0, 144.4, 142.3, 141.1, 128.5, 128.1, 127.9, 127.3, 125.6, 124.9, 118.4, 115.1; IR (KBr) ν: 1594, 1539, 1470, 1422, 854, 826, 738, 709 cm^－1; HRMS (EI) calcd for C₁₃H₁₀S₂N 224.0249, found 224.0252.

  3, 5-Dimethyl-2, 6-diphenylpyridine (3a): White solid, 42 mg, 65% yield, m.p. 128~131 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.58 (d, J＝7.4 Hz, 4H), 7.47 (s, 1H), 7.42 (t, J＝7.4 Hz, 4H), 7.35 (t, J＝7.2 Hz, 2H), 2.37 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 155.8, 141.2, 140.6, 129.3, 129.2, 128.1, 127.7, 19.6; IR (KBr) ν: 1441, 1420, 1390, 775, 763, 702, 607 cm^－1; HRMS (EI) calcd for C₁₉H₁₈N 260.1434, found 260.1437.

  2, 6-Bis(4-methoxyphenyl)-3, 5-dimethylpyridine (3b): White solid, 57 mg, 71% yield. m.p. 108~110 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.46 (d, J＝8.0 Hz, 4H), 7.35 (s, 1H), 6.86 (d, J＝8.1 Hz, 4H), 3.75 (s, 6H), 2.29 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 159.3, 155.3, 141.3, 133.2, 130.5, 128.6, 113.5, 55.3, 19.8; IR (KBr) ν: 1609, 1512, 1461, 1427, 1248, 1176, 1029, 837 cm^－1; HRMS (EI) calcd for C₂₁H₂₂NO₂ 320.1645, found 320.1647.

  3, 5-Dimethyl-2, 6-di-p-tolylpyridine (3c): Yellow oil, 49 mg, 68% yield. m.p. 100~103 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.40 (d, J＝7.7 Hz, 4H), 7.35 (s, 1H), 7.14 (d, J＝7.8 Hz, 4H), 2.30 (s, 6H), 2.28 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 155.7, 141.2, 137.3, 132.1, 129.9, 129.2, 128.7, 21.3, 19.7; IR (KBr) ν: 1621, 1534, 1426, 908, 826, 732 cm^－1; HRMS (EI) calcd for C₂₁H₂₂N 288.1747, found 288.1748.

  2, 6-Bis(4-chlorophenyl)-3, 5-dimethylpyridine (3d): White solid, 49 mg, 60% yield. m.p. 138~139 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.51 (d, J＝8.0 Hz, 4H), 7.49 (s, 1H), 7.40 (d, J＝7.7 Hz, 4H), 2.36 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 154.6, 141.6, 138.7, 133.9, 130.6, 129.5, 128.4, 19.6; IR (KBr) ν: 1608, 1557, 1495, 1454, 1093, 831, 767 cm^－1; HRMS (EI) calcd for C₁₉H₁₆NCl₂ 328.0654, found 328.0656.

  2, 6-Diphenyl-3, 5-dipropylpyridine (3e): White solid, 42 mg, 54% yield. m.p. 139~142 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.52 (d, J＝7.5 Hz, 4H), 7.41 (t, J＝7.3 Hz, 4H), 7.38~7.32 (m, 2H), 2.68~2.60 (m, 4H), 1.65~1.53 (m, 4H), 0.90 (t, J＝7.3 Hz, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 155.6, 139.1, 134.2, 134.1, 129.2, 128.1, 127.7, 34.2, 24.2, 14.0; IR (KBr) ν: 2968, 1437, 1372, 775, 736, 699, 643 cm^－1; HRMS (EI) calcd for C₂₃H₂₆N 316.2060, found 316.2058.

  (2, 6-Diphenylpyridine-3, 5-diyl)bis(phenylmethanone) (3f): White solid, 71 mg, 65% yield, m.p. 181~184 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.05 (s, 1H), 7.74 (d, J＝7.8 Hz, 4H), 7.72~7.66 (m, 4H), 7.46 (t, J＝7.3 Hz, 2H), 7.32 (t, J＝7.8 Hz, 4H), 7.30~7.26 (m, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 196.7, 158.1, 138.9, 138.6, 136.4, 133.6, 131.9, 129.9, 129.6, 129.5, 128.5, 128.4; IR (KBr) ν: 1663, 1594, 1528, 1320, 1247, 1008, 911, 766, 748, 725, 712, 689 cm^－1; HRMS (EI) calcd for C₃₁H₂₂NO₂ 440.1645, found 440.1647.

  5, 6, 8, 9-Tetrahydrodibenzo[c, h]acridine (3g): Yellow solid, 45 mg, 64% yield. m.p. 163~166 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 8.51 (d, J＝7.6 Hz, 2H), 7.39 (t, J＝7.5 Hz, 2H), 7.30 (t, J＝7.3 Hz, 3H), 7.23 (t, J＝6.2 Hz, 2H), 2.94 (s, 8H); ¹³C NMR (CDCl₃, 100 MHz) δ: 150.4, 137.9, 135.3, 135.0, 130.6, 128.6, 127.7, 127.1, 125.0, 28.3, 27.9; IR (KBr) ν: 2922, 2832, 1552, 1435, 1418, 1237, 801, 747, 721 cm^－1; HRMS (EI) calcd for C₃₁H₂₂NO₂ 284.1434, found 284.1435.

  Supporting Information    ¹H NMR and ¹³C NMR spectra for all products. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn.

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• 

  Scheme 1  Control experiments

  下载: 全尺寸图片 幻灯片
  

  Figure 1  Possible mechanism

  下载: 全尺寸图片 幻灯片

  Table 1.  Optimization of reaction conditions

  Entry	N source	Catalyst	Temp./℃	Yieldb/%
  1	NH4OAc	T(p-MeO)PPFeCl	120	72
  2	NH4OAc	T(p-Cl)PPFeCl	120	65
  3	NH4OAc	T(p-Me)PPFeCl	120	67
  4	NH4OAc	TPPFeCl	120	62
  5	NH4OAc	—	120	12
  6	NH4OAc	T(p-MeO)PPCu	120	51
  7	NH4OAc	T(p-MeO)PPCo	120	38
  8	NH4OAc	T(p-MeO)PPMnCl	120	42
  9	NH4OAc	T(p-MeO)PPNi	120	26
  10	(NH4)2CO3	T(p-MeO)PPFeCl	120	42
  11	NH4HCO3	T(p-MeO)PPFeCl	120	40
  12	NH3•H2O	T(p-MeO)PPFeCl	120	36
  13	NH4I	T(p-MeO)PPFeCl	120	18
  14	HCOONH4	T(p-MeO)PPFeCl	120	65
  15	NH4OAc	T(p-MeO)PPFeCl	100	47
  16	NH4OAc	T(p-MeO)PPFeCl	130	70
  17c	NH4OAc	T(p-MeO)PPFeCl	120	63
  18d	NH4OAc	T(p-MeO)PPFeCl	120	69
  a Reaction conditions: acetophenone (1a, 0.5 mmol), N source (1.5 mmol), catalyst (1.0 mol%) and solvent (2 mL) for 24 h under O2 atmosphere at 120 ℃. b Isolated yield. c T(p-MeO)PPFeCl (0.5 mol%). d T(p-MeO)PPFeCl (2.0 mol%).

  下载: 导出CSV

  Table 2.  Scope of acetophenones

  Entry	(Het)Ar	2	Yield/%
  1	Ph	2a	72
  2	4-MeOC6H4	2b	81
  3	4-EtOC6H4	2c	85
  4	4-MeC6H4	2d	78
  5	3-MeC6H4	2e	73
  6	2-MeC6H4	2f	42
  7	3, 4-(MeO)2C6H3	2g	82
  8	2, 4-(MeO)2C6H3	2h	71
  9	4-FC6H4	2i	58
  10	4-ClC6H4	2j	70
  11	4-BrC6H4	2k	66
  12	3-BrC6H4	2l	54
  13	2-BrC6H4	2m	34
  14	4-IC6H4	2n	54
  15	3-NO2C6H4	2o	35
  16	4-CNC6H4	2p	66
  17	4-CF3C6H4	2q	58
  18	2-Naphthyl	2r	68
  19	Furyl	2s	52
  a Standard conditions: ketones (0.5 mmol), NH4OAc (3.0 equiv.), T(p-MeO)- PPFeCl (1.0 mol%), DMSO (2.0 mL), 120 ℃ for 24 h. b Isolated yield.

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  Table 3.  Scope of acetophenones

  Entry	Ar	1	Yield/%
  			2a	2'b
  1	2-CH3C6H4	1f	42 (2f)	40 (2f')
  2	2-BrC6H4	1m	34 (2m)	38 (2m')
  3	3-NO2C6H4	1o	35 (2o)	30 (2o')
  a Standard conditions: ketones (0.5 mmol), NH4OAc (3.0 equiv.), T(p-MeO)- PPFeCl (1.0 mol%), DMSO (2.0 mL), 120 ℃ for 24 h. b Isolated yield.

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  Table 4.  Scope of α-substituent ketones

  Entry	R1	R2	1	3	Yieldb/%
  1	Ph	Me	1t	3a	65
  2	4-MeOC6H4	Me	1u	3b	71
  3	4-MeC6H4	Me	1v	3c	68
  4	4-ClC6H4	Me	1w	3d	60
  5	Ph	n-Pr	1x	3e	54
  6	Ph	PhC＝O	1y	3f	65
  7	CH2＝CHC6H4	H	1z		0
  8	Ph	Ph	1af		0
  9			1ag	3g	64
  10			1ah		0
  a Standard conditions: ketones (0.5 mmol), NH4OAc (3.0 equiv.), T(p-OMe)- PPFeCl (1.0 mol%), DMSO (2.0 mL), 120 ℃ for 24 h. b Isolated yield.

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