English

• 1.   Introduction

  Functionalized 1-naphthylamine compounds have been recognized as important molecules which could potentially be applied as ligand, fluorescent probes and bioactive molecule.^[1] The selective C—H bond activation of 1-naph- thylamine has emerged as an attractive method to construct corresponding 1-naphthylamine derivatives.^[2~12] Various types of C(8)-functionalizations of 1-naphthylmide derivatives such as arylation, ^[4] alkylation, ^[5] alkenylation, ^[6] amination, ^[7] heteroarylation, ^{[7a, 8]} chalcogenation, ^[9] and cyanation^[10] have been developed using Pd, Cu and Rh catalysts. In terms of etherification, Daugulis and co-workers^[11] first reported the C(8)-phenoxylation of 1-naphthylamide mediated by copper through a bidentate-picolinamide moiety as a directing group. Recently, Punniyamurthy and co-workers^[12] reported the Cu-catalyzed C(8)-phenoxyla- tion of naphthylamides with arylboronic acids using water as an oxygen source. However, taking advantage of transition-metal catalyzed C—H bond activation, directed C(8)-alkoxylation of 1-naphthylamide using alcohol as alkoxylation reagent has rarely been explored, due to the alkoxyl-metal intermediates formed tend to undergo β-H elimination.^[13]

  Recently, Co-catalyzed C—H activation has received increasing attention in organic synthesis because of its inexpensive and sustainable. And much progress has been made in constructing C—C and C—X bonds mediated by cobalt, and which has been reviewed by Ackermann^[14], Niu^[15] and others^{[16, 17]}. Inspired by cobalt-catalyzed C—O bond construction of arenes and alkenes, reported by Song, ^[18] Zeng, ^[19] Zhang, ^[20] Wu, ^[21] Chatani, ^[22] and Acker- mann, ^[23] respectively, we speculated that a cobalt catalyst might also promote the C(8)-alkoxylation of N-(naphthalen- 1-yl)picolinamide applying alcohols, especially diols, as alkoxylation reagents.

  2.   Results and discussion

  To probe the feasibility of this approach, initially, the reaction of N-(naphthalen-1-yl)picolinamide (1) with methanol (2a) was explored in the presence of Co(OAc)₂ (30 mol%), Ag₂CO₃ (2.0 equiv.) and KOAc (2.0 equiv.). As expected, the desired N-(8-methoxynaphthalen-1-yl)pico- linamide (3a) was obtained in 32% yield (Table 1, Entry 1) and the structure of 3a was further confirmed by X-ray crystallography.^[24] Other catalysts were investigated including CoCl₂, Co₂(CO)₈, Co(acac)₂ and Pd(OAc)₂. It was found that CoCl₂ and Co₂(CO)₈ failed to give a better yield than Co(OAc)₂, and no desired product was achieved when Co(acac)₂ and Pd(OAc)₂ were introduced (Table 1, Entries 2~5). Different oxidants were also examined in this transformation and Mn(OAc)₂ was proved to be the best oxidant giving 3a in 61% yield (Table 1, Entries 6~10). Na₂CO₃, K₂CO₃ and Cs₂CO₃ were found to be inferior compared to KOAc for providing 3a in 25%, 28%, and 30% yields (Table 1, Entries 10~13), respectively, and it was noteworthy that 8-(picolinamido)naphthalen-1-yl acetate reported by Zeng^[19] was not detected, even though the amount of KOAc was increased to 10 equiv. (Table 1, Entry 14). The control experiments indicated that the cobalt catalyst and oxidant were essential, as no reaction took place in the absence of Co(OAc)₂ and Mn(OAc)₂ (Table 1, Entries 15, 16). The reaction was less active when phase transfer catalysts were added (Table 1, Entries 17~20). The addition of other solvent, such as toluene and O-chlorotoluene, the yield was reduced significantly (Table 1, Entries 21, 22). It was found that the yield was decreased when the amount of Co(OAc)₂ was reduced (Table 1, Entries 23, 24). Finally, the optimized reaction conditions were obtained: Co(OAc)₂ (30 mol%), Mn(OAc)₂ (2.0 equiv.), KOAc (2.0 equiv.) in MeOH (1.0 mL) at 80 ℃ for 12 h.

  Table 1

  

  Table 1.  Optimization of the reaction conditions^a

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  Entry	Cat.	Oxidant	Base	Additive	Yieldb/%
  1	Co(OAc)2	Ag2CO3	KOAc	—	32
  2	CoCl2	Ag2CO3	KOAc	—	12
  3	Co2(CO)8	Ag2CO3	KOAc	—	21
  4	Co(acac)2	Ag2CO3	KOAc	—	NR
  5	Pd(OAc)2	Ag2CO3	KOAc	—	NR
  6	Co(OAc)2	Ag2O	KOAc	—	40
  7	Co(OAc)2	AgOAc	KOAc	—	20
  8	Co(OAc)2	AgOTFA	KOAc	—	23
  9	Co(OAc)2	Mn(OAc)2•2H2O	KOAc	—	17
  10	Co(OAc)2	Mn(OAc)2	KOAc	—	61
  11	Co(OAc)2	Mn(OAc)2	Na2CO3	—	25
  12	Co(OAc)2	Mn(OAc)2	K2CO3	—	28
  13	Co(OAc)2	Mn(OAc)2	Cs2CO3	—	30
  14	Co(OAc)2	Mn(OAc)2	KOAc	—	43c
  15	—	Mn(OAc)2	KOAc	—	0
  16	Co(OAc)2	—	KOAc	—	0
  17	Co(OAc)2	Mn(OAc)2	KOAc	n-Bu4NI	13
  18	Co(OAc)2	Mn(OAc)2	KOAc	n-Bu4NOAc	21
  19	Co(OAc)2	Mn(OAc)2	KOAc	n-Bu4NPF6	26
  20	Co(OAc)2	Mn(OAc)2	KOAc	18-Crown-6	38
  21	Co(OAc)2	Mn(OAc)2	KOAc	—	19d
  22	Co(OAc)2	Mn(OAc)2	KOAc	—	21e
  23	Co(OAc)2	Mn(OAc)2	KOAc	—	44 f
  24	Co(OAc)2	Mn(OAc)2	KOAc	—	13 g
  a Reaction conditions unless otherwise specified: 1 (0.1 mmol), catalyst (30 mol%), oxidant (2.0 equiv.), base (2.0 equiv.), additive (2.0 equiv.), MeOH (1 mL), 80 ℃ under air for 12 h. b Isolated yield. c The amount of KOAc was increased to 10 equiv. d Used toluene as the solvent and the volume ratio of MeOH and toluene was 1:1 (1.0 mL). e Used O-chlorotoluene as the solvent and the volume ratio of MeOH and O-chlorotoluene was 1:1 (1.0 mL). f The amount of Co(OAc)2 was reduced to 20 mol%. g The amount of Co(OAc)2 was reduced to 10 mol%.

  With the optimized conditions established, we began to examine the scope of the reaction with respect to various alcohols. A variety of linear, branched, monohydric alcohol and glycol were well applicable to give corresponding alkoxylated products 3a~3s. Among simple primary alkyl alcohols, methanol, ethanol, propanol, butanol, pentanol, hexanol, heptanol, hexanol gave the desired products in higher yields (Table 2, Entries 1~7). Trifluoroethanol underwent reaction with 1 to form the desired product 3h in low yield under the standard condition. When the oxidant was replaced by Ag₂CO₃, the reaction yield was increased to 53% (Table 2, Entry 8). Moreover, phenylethanol was proved to be effective coupling partners to provide 3i in 72% yields (Table 2, Entry 9). Gratifyingly, secondary alcohol, such as cyclopentanol 2j could react with 1 to afford the desired product 3j in 66% yield (Table 2, Entry 10). It was worth noting that not only alcohol, but also phenol could act as an alkoxylating reagent, affording the corresponding product 3k in 43% yield (Table 2, Entry 11).

  Table 2

  

  Table 2.  Cobalt-catalyzed alkoxylation of 1-naphthylamine derivative with various alcohols^a

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  Glycol compounds were always applied as reducing regent in heterogeneous coupling reaction, ligands in transition metal catalyzed coupling reaction, detection groups in fluorescent probes, phase transfer catalysts in organic synthesis and chemical raw materials in polymer preparation, ^[25] therefore, we turned our interest to explore the reactivity of glycol under our reaction condition. To our delight, various glycol, such as ethylene glycol, 1, 3-pro- panediol, 1, 4-butanediol, 1, 3-butanediol, diethylene glycol and triethylene glycol could reacted with 1 to afford the corresponding products in mediated yield (Table 2, Entries 12~17). It is worth noting that the yield of 3n was improved to 75% when n-Bu₄NPF₆ was added (Table 2, Entry 14). Unfortunately, this phase transfer catalyst has no effect on other glycols. Moreover, when the butane- 1, 3-diol (2o) was employed, the desired product was obtained at the position of primary alcohol and no isomer was observed (Table 2, Entry 15). After further research, we found that ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, and diethylene glycol monomethyl ether were all tolerated in this transformation, affording the desired compound in 65%~76% yields (Table 2, Entries 18~20).

  The deuterium labeled organic compounds are widely used in analytical chemistry, biochemistry and medicinal chemistry.^[26] Therefore, we directly synthesized the deuterated methoxy substituted N-(naphthalen-1-yl)picolin-amide (3a') when d⁴-deuterated methanol instead of methanol in the standard condition (Scheme 1).

  Scheme 1

  

  Scheme 1.  Preparation of deuterium labeled methoxylated 1-naphthylamide

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  The substrate scope of 1-naphthylamine derivatives was explored as shown in Scheme 2. The results showed that the picolinoyl group was the best directing group for this reaction compared to benzoyl and quinoline-2-carbonyl. Halogenated 1-naphthylamine could afford the desired product in low yield and no target product was detected when nitro-substituted 1-naphthylamine was used as sub- strate.

  Scheme 2

  

  Scheme 2.  Reaction scope of 1-naphthylamine derivatives

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  The directing group was easily removed, and the 8-butoxynaphthalen-1-amine 4 and picolinic acid were obtained (Scheme 3). Furthermore, the ultraviolet absorption spectrum demonstrated that the C(8)-alkoxylated 1-naphthylamine showed a red shifted absorption compared to N-(naphthalen-1-yl)picolinamide.

  Scheme 3

  

  Scheme 3.  Removal the directing group

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  Control experiments were carried out to gain some insight into the possible mechanism (Eqs. 1~4). Initially, the addition of radical scavengers, such as (2, 2, 6, 6-tetra- methylpiperidin-1-yl)oxy (TEMPO) and 1, 4-benzoquinone (BQ), significantly inhibited the reaction, suggesting that a radical pathway may be involved in the reaction and the mechanism likely proceeds via an intermolecular single-electron transfer (SET) process^{[18, 21, 23, 27, 28]} (Eq. 1). Then, the Co(Ⅱ)-catalyzed alkoxylation reaction of N-naphthalen-1-yl-benzamide (1) and MeOH (2a) was performed in presence of 1.0 equiv. Co(OAc)₂ and no desired aryl C—H methoxylated product 3a was formed (Eq. 2). This experiment demonstrated that the active Co(Ⅲ) species was possibly involved in this transformation. A kinetic isotope effect (KIE) of 1.20 (k_H/k_D) was determined through parallel experiments, indicated that C(sp²)—H bond-breaking was not the rate-determining step (Eq. 3). Furthermore, no D/H exchange was observed when 1a was treated with deuterated methanol under standard conditions (Eq. 4). These results may suggest that the C-H cleavage is irreversible.

  3.   Conclusions

  In summary, we have developed a cobalt-catalyzed direct alkoxylation of 1-naphthylamide with various alcohols via picolinamide directed C(8)—H activation and C—O bond formation, providing a convenient method to C(8)-alko- xylated 1-naphthylamide. A series of alcohols, including monohydric alcohols, glycol, diethylene glycol, and deuterated alcohol were found to be applicable to the reaction. In addition, the directing group was removed under mild reaction and the introduction of alkoxy group at C(8) of 1-naphthylaminde promoted the red shift of UV absorption. Moreover, the mechanistic investigation suggests that this C—H alkoxylation reaction might proceed via a single-electron-transfer process.

  (1)

  (2)

  (3)

  (4)

  4.   Experimental

  4.1   General

  The reagents and solvents were purchased from common commercial sources and used without additional purification, if there is no special version. The starting materials of N-(naphthalen-1-yl)picolinamide were prepared according to the known methods.^{[2~12, 17]} NMR spectra were recorded for ¹H NMR at 400 MHz, and ¹³C NMR at 100 MHz using TMS as internal standard. Mass spectroscopy data of the products were collected on an Xevo G2-XS QTof (Waters).

  4.2   General procedure for preparation of products 3

  A 25 mL sealed tube with a magnetic stir bar was charged with Co(OAc)₂ (30 mol%), Mn(OAc)₂ (2.0 equiv.), KOAc (2.0 equiv.), 1 (0.1 mmol), alcohol (1 mL). Then the sealed tube was sealed and heated to 80 ℃ with stirring for 12 h. After cooling down, the mixture was filtered through a plug of Celite, and then the residue was concentrated and purified by flash column chromatography with ethyl acetate and petroleum ether as eluent to afford the corresponding products.

  4.3   General procedure for preparation of products 3h

  A 25 mL sealed tube with a magnetic stir bar was charged with Co(OAc)₂ (30 mol%), Ag₂CO₃ (2.0 equiv.), KOAc (2.0 equiv.) and 1 (0.1 mmol), 2, 2, 2-trifluoroethanol (1 mL). Then the sealed tube was sealed and heated to 80 ℃ with stirring for 12 h. After cooling down, the mixture was filtered through a plug of Celite, and then the residue was concentrated and purified by flash column chromatography with ethyl acetate and petroleum ether as eluent to afford the corresponding products.

  4.4   General procedure for preparation of products 3n

  A 25 mL sealed tube with a magnetic stir bar was charged with Co(OAc)₂ (30 mol%), Ag₂CO₃ (2.0 equiv.), KOAc (2.0 equiv.), n-Bu₄NPF₆ (2.0 equiv.), 1 (0.1 mmol) and butane-1, 4-diol (1 mL). Then the sealed tube was sealed and heated to 80 ℃ with stirring for 12 h. After cooling down, the mixture was filtered through a plug of Celite, and then the residue was concentrated and purified by flash column chromatography with ethyl acetate and petroleum ether as eluent to afford the corresponding products.

  4.5   General procedure for preparation of products 4

  A 25 mL sealed tube with a magnetic stir bar was charged with 3d (0.1 mmol), NaOH (2 mmol) and MeOH (1 mL). Then the sealed tube was sealed and heated to 80 ℃ with stirring for 12 h. After cooling down, the mixture was concentrated, and then the residue was extracted with ethyl acetate and water. The organic layer was collected and dried over Na₂SO₄. After concentrated in vacuum and the residue was purified by flash column chromatography with ethyl acetate and petroleum ether as eluent to afford the corresponding products.

  4.6   Isotopically labeled experiment

  4.6.1   Kinetic isotope effect of this transformation

  A 25 mL sealed tube with a magnetic stir bar was charged with Co(OAc)₂ (30 mol%), Mn(OAc)₂ (2.0 equiv.), KOAc (2.0 equiv.), 1 (0.1 mmol) or d-1a (0.1 mmol) and MeOH (1 mL). Then the sealed tube was sealed and heated to 80 ℃ with stirring for 6 h. After cooling down, the mixture was filtered through a plug of Celite, and then the residue was concentrated and purified by flash column chromatography with ethyl acetate and petroleum ether as eluent to afford the corresponding products.

  4.6.2   H/D exchange experiment

  A 25 mL sealed tube with a magnetic stir bar was charged with Co(OAc)₂ (30 mol%), Mn(OAc)₂ (2.0 equiv.), KOAc (2.0 equiv.), 1 (0.1 mmol) and CD₃OD (1.0 mL). Then the sealed tube was sealed and heated to 80 ℃ with stirring for 6 h. After cooling down, the mixture was filtered through a plug of Celite, and then the residue was concentrated and purified by flash column chromatography with ethyl acetate and petroleum ether as eluent to afford the corresponding products.

  4.7   Characterization data of the products

  N-(8-Methoxynaphthalen-1-yl)picolinamide (3a): light yellow solid (17 mg, 61% yield), m.p. 174~175; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 4.20 (s, 3H), 6.91 (d, J＝8.0 Hz, 1H), 7.35~7.39 (m, 1H), 7.44~7.50 (m, 2H), 7.53 (d, J＝8.0 Hz, 1H), 7.56~7.58 (m, 1H), 7.91 (td, J＝8.0, 1.6 Hz, 1H), 8.35 (d, J＝8.0 Hz, 1H), 8.69~8.70 (m, 1H), 9.01 (dd, J＝8.0, 1.2 Hz, 1H), 13.24 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 56.2, 105.7, 116.6 (2C), 122.0, 122.6, 123.7, 125.6, 126.0, 126.8, 135.2, 136.4, 137.5, 148.0, 151.2, 156.2, 162.4; IR (film) ν: 2958, 2925, 2855, 1667, 1544, 1499, 1291 cm^－1; HRMS (ESI) calcd for C₁₇H₁₅N₂O₂ [M+H]⁺ 279.1128, found 279.1121.

  N-(8-Ethoxynaphthalen-1-yl)picolinamide (3b): White solid (14 mg, 48% yield), m.p. 117~118 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 1.72 (t, J＝6.0 Hz, 3H), 4.40 (q, J＝8.0 Hz, 2H), 6.94 (d, J＝8.0 Hz, 1H), 7.36 (dd, J＝8.0, 8.0 Hz, 1H), 7.44~7.50 (m, 2H), 7.53 (d, J＝8.0 Hz, 1H), 7.58 (d, J＝8.0 Hz, 1H), 7.92 (td, J＝8.0, 2.0 Hz, 1H), 8.37 (d, J＝8.0 Hz, 1H), 8.65~8.66 (m, 1H), 9.01 (d, J＝8.0 Hz, 1H), 12.77 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 15.1, 65.4, 106.8, 117.0, 117.2, 121.9, 122.7, 124.0, 125.6, 126.1, 126.6, 135.0, 136.5, 137.4, 147.7, 151.1, 155.6, 162.8; IR (film) ν: 3052, 2924, 2848, 1671, 1527, 1490, 1271 cm^－1; HRMS (ESI) calcd for C₁₈H₁₇N₂O₂ [M+H]⁺ 293.1285, found 293.1280.

  N-(8-Propoxynaphthalen-1-yl)picolinamide (3c): White solid (11 mg, 36% yield), m.p. 85~86 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 1.06 (t, J＝6.0 Hz, 3H), 2.12~2.21 (m, 2H), 4.31 (t, J＝6.0 Hz, 2H), 6.94 (d, J＝8.0 Hz, 1H), 7.36 (dd, J＝8.0, 8.0 Hz, 1H), 7.44~7.54 (m, 3H), 7.57~7.60 (m, 1H), 7.93 (td, J＝8.0, 4.0 Hz, 1H), 8.37 (d, J＝8.0 Hz, 1H), 8.66~8.67 (m, 1H), 9.00 (d, J＝8.0 Hz, 1H), 12.75 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 10.8, 22.3, 71.5, 106.8, 117.1, 117.2, 121.8, 122.8, 124.0, 125.6, 126.1, 126.6, 135.0, 136.5, 137.4, 147.6, 151.2, 155.7, 162.8; IR (film) ν: 2955, 2924, 2849, 1682, 1535, 1494, 1275 cm^－1; HRMS (ESI) calcd for C₁₉H₁₉N₂O₂ [M+H]⁺ 307.1441, found 307.1445.

  N-(8-Butoxynaphthalen-1-yl)picolinamide (3d): White solid (23 mg, 73% yield), m.p. 109~110 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 0.93 (t, J＝8.0 Hz, 3H), 1.44~1.53 (m, 2H), 2.08~2.15 (m, 2H), 4.33 (t, J＝8.0 Hz, 2H), 6.94 (d, J＝8.0 Hz, 1H), 7.36 (dd, J＝8.0, 8.0 Hz, 1H), 7.45 (d, J＝8.0 Hz, 1H), 7.47~7.50 (m, 1H), 7.52~7.53 (m, 1H), 7.58 (d, J＝8.0 Hz, 1H), 7.92 (td, J＝8.0, 0.8 Hz, 1H), 8.37 (d, J＝8.0 Hz, 1H), 8.67 (d, J＝8.0 Hz, 1H), 9.00 (d, J＝8.0 Hz, 1H), 12.73 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 13.9, 19.3, 31.0, 69.7, 106.8, 117.1, 117.2, 121.8, 122.8, 124.0, 125.6, 126.1, 126.6, 135.0, 136.5, 137.4, 147.7, 151.2, 155.7, 162.8; IR (film) ν: 2951, 2920, 2852, 1660, 1532, 1456, 1373 cm^－1; HRMS (ESI) calcd for C₂₀H₂₁N₂O₂ [M+H]⁺ 321.1598, found 321.1594.

  N-(8-(Pentyloxy)naphthalen-1-yl)picolinamide (3e): White solid (26 mg, 78% yield), m.p. 109~110 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 0.86 (t, J＝8.0 Hz, 3H), 1.29~1.38 (m, 2H), 1.39~1.47 (m, 2H), 2.10~2.17 (m, 2H), 4.33 (t, J＝8.0 Hz, 2H), 6.94 (d, J＝8.0 Hz, 1H), 7.36 (dd, J＝8.0, 8.0 Hz, 1H), 7.45 (d, J＝8.0 Hz, 1H), 7.48~7.54 (m, 2H), 7.58 (d, J＝8.0 Hz, 1H), 7.93 (td, J＝8.0, 2.0 Hz, 1H), 8.37 (d, J＝8.0 Hz, 1H), 8.67 (d, J＝8.0 Hz, 1H), 8.99 (d, J＝8.0 Hz, 1H), 12.73 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 14.1, 22.5, 28.3, 28.7, 70.0, 106.8, 117.1, 117.2, 121.8, 122.8, 124.0, 125.6, 126.1, 126.6, 135.0, 136.5, 137.5, 147.7, 151.2, 155.7, 162.8; IR (film) ν: 2954, 2913, 2852, 1675, 1532, 1462, 1377 cm^－1; HRMS (ESI) calcd for C₂₁H₂₃N₂O₂ [M+H]⁺ 335.1754, found 335.1763.

  N-(8-(Hexyloxy)naphthalen-1-yl)picolinamide (3f): White solid (30 mg, 86% yield), m.p. 80~82 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 0.86 (t, J＝6.0 Hz, 3H), 1.24~1.34 (m, 4H), 1.43~1.48 (m, 2H), 2.11~2.18 (m, 2H), 4.36 (t, J＝6.0 Hz, 2H), 6.97 (d, J＝8.0 Hz, 1H), 7.39 (dd, J＝8.0, 8.0 Hz, 1H), 7.47 (d, J＝8.0 Hz, 1H), 7.51~7.55 (m, 2H), 7.59~7.61 (m, 1H), 7.96 (dd, J＝6.0, 6.0 Hz, 1H), 8.39 (d, J＝8.0 Hz, 1H), 8.70 (d, J＝4.0 Hz, 1H), 8.99~9.01 (m, 1H), 12.75 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 13.9, 22.6, 25.8, 29.0, 31.6, 70.0, 106.9, 117.1, 117.2, 121.8, 122.8, 124.0, 125.6, 126.1, 126.6, 135.0, 136.5, 137.4, 147.7, 151.3, 155.7, 162.7; IR (film) ν: 2950, 2925, 2852, 1675, 1532, 1427, 1279 cm^－1; HRMS (ESI) calcd for C₂₂H₂₅N₂O₂ [M+H]⁺ 349.1911, found 349.1910.

  N-8-(Heptyloxy)naphthalen-1-yl)picolinamide (3g): White solid (32 mg, 88% yield), m.p. 87~89 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 0.85 (t, J＝6.0 Hz, 3H), 1.18~1.27 (m, 4H), 1.28~1.33 (m, 2H), 1.40~1.47 (m, 2H), 2.09~2.16 (m, 2H), 4.33 (t, J＝8.0 Hz, 2H), 6.95 (d, J＝8.0 Hz, 1H), 7.37 (dd, J＝8.0, 8.0 Hz, 1H), 7.44~7.46 (m, 1H), 7.48~7.53 (m, 2H), 7.57~7. 60 (m, 1H), 7.93 (td, J＝8.0, 1.6 Hz, 1H), 8.37 (d, J＝8.0 Hz, 1H), 8.67~8.68 (m, 1H), 8.98~9.00 (m, 1H), 12.73 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 14.1, 22.6, 26.1, 29.0, 29.1, 31.8, 70.0, 106.8, 117.1, 117.2, 121.8, 122.8, 124.0, 125.6, 126.1, 126.6, 135.0, 136.5, 137.5, 147.7, 151.2, 155.7, 162.8; IR (film) ν: 2950, 2921 2856, 1532, 1471, 1377, 1058 cm^－1; HRMS (ESI) calcd for C₂₃H₂₇N₂O₂ [M+H]⁺ 363.2067, found 363.2070.

  N-(8-(2, 2, 2-Trifluoroethoxy)naphthalen-1-yl)picolina-mide (3h): White solid (18 mg, 53% yield), m.p. 201~202 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 4.78 (q, J＝8.0 Hz, 2H), 7.07 (d, J＝8.0 Hz, 1H), 7.40 (dd, J＝8.0, 8.0 Hz, 1H), 7.48~7.51 (m, 1H), 7.53~7.63 (m, 3H), 7.93 (dd, J＝8.0, 8.0 Hz, 1H), 8.35 (d, J＝8.0 Hz, 1H), 8.66~8.67 (m, 1H), 8.95 (d, J＝4.0 Hz, 1H), 12.53 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 68.0, 68.4, 68.7, 69.1, 109.8, 117.3, 118.1, 122.5, 124.2, 124.5, 125.4, 126.3, 127.1, 134.1, 136.5, 137.5, 148.1, 150.7, 154.8, 162.7; IR (film) ν: 2958, 2920, 2860, 1667, 1547, 1468, 1317 cm^－1; HRMS (ESI) calcd for C₁₈H₁₄F₃N₂O₂ [M+H]⁺ 347.1002, found 347.1003.

  N-(8-Phenethoxynaphthalen-1-yl)picolinamide (3i): White solid (28 mg, 80% yield), m.p. 134~136 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 3.49 (t, J＝8.0 Hz, 2H), 4.54 (t, J＝6.0 Hz, 2H), 6.95 (d, J＝8.0 Hz, 1H), 7.20~7.26 (m, 1H), 7.30 (d, J＝4.0 Hz, 4H), 7.36 (dd, J＝8.0, 8.0 Hz, 1H), 7.44~7. 49 (m, 2H), 7.53 (dd, J＝8.0, 8.0 Hz, 1H), 7.59~7.61 (m, 1H), 7.92 (td, J＝8.0, 1.6 Hz, 1H), 8.35~8.38 (m, 1H), 8.60~8.61 (m, 1H), 9.00~9.03 (m, 1H), 12.76 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 35.7, 70.7, 107.0, 117.3, 122.2, 122.8, 124.1, 125.6, 126.2, 126.7 (2C), 128.7, 129.0, 134.9, 136.5, 137.5, 137.8, 147.7, 155.3, 162.7; IR (film) ν: 3027, 2933, 2872, 1597, 1499, 1450, 1046 cm^－1; HRMS (ESI) calcd for C₂₄H₂₁N₂O₂ [M+H]⁺ 369.1598, found 369.1560.

  N-(8-(Cyclopentyloxy)naphthalen-1-yl)picolinamide (3j): light yellow solid (22 mg, 66% yield), m.p. 138~139 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 1.62~1.69 (m, 2H), 1.78~1.86 (m, 2H), 2.05~2.14 (m, 2H), 2.31~2.39 (m, 2H), 5.08~5.13 (m, 1H), 6.94~6.96 (m, 1H), 7.36 (dd, J＝8.0, 8.0 Hz, 1H), 7.42~7.44 (m, 1H), 7.48~7.52 (m, 2H), 7.57~7.59 (m, 1H), 7.93 (td, J＝8.0, 1.6 Hz, 1H), 8.36~8.39 (m, 1H), 8.65~8.67 (m, 1H), 8.93~8.96 (m, 1H), 12.36 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 24.7 (2C), 32.8, 81.3, 108.2, 117.6, 121.5, 123.0, 124.2, 125.5, 126.1 (2C), 126.3, 134.8, 136.6, 137.4, 147.5, 151.3, 154.8, 163.0; IR (film) ν: 2954, 2925, 2848, 1679, 1532, 1458, 1270 cm^－1; HRMS (ESI) calcd for C₂₁H₂₁N₂O₂ [M+H]⁺ 333.1598, found 333.1560.

  N-(8-Phenoxynaphthalen-1-yl)picolinamide (3k): White solid (15 mg, 43% yield), m.p. 116~118 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 6.99 (dd, J＝8.0, 1.2 Hz, 1H), 7.18~7.23 (m, 1H), 7.24~7.29 (m, 2H), 7.34~7.38 (m, 2H), 7.40~7.45 (m, 2H), 7.58~7.64 (m, 2H), 7.67 (dd, J＝8.0, 1.2 Hz, 1H), 7.82~7.86 (m, 1H), 8.27~8.30 (m, 2H), 9.07 (dd, J＝8.0, 1.2 Hz, 1H), 13.05 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 114.0, 117.0, 117.9, 120.1, 122.2, 124.0, 124.2, 125.6, 126.0, 126.9, 129.7, 134.6, 136.6, 137.3, 147.7, 150.5, 154.2, 156.6, 162.7; IR (film) ν: 2983, 2941, 2888, 1689, 1531, 1493, 1232 cm^－1; HRMS (ESI) calcd for C₂₂H₁₇N₂O₂ [M+H]⁺ 341.1285, found 341.1282.

  N-(8-(2-Hydroxyethoxy)naphthalen-1-yl)picolinamide (3l): White solid (15 mg, 48% yield), m.p. 141~142 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 4.23 (t, J＝4.0 Hz, 2H), 4.34 (t, J＝4.0 Hz, 2H), 6.96 (d, J＝8.0 Hz, 1H), 7.38 (dd, J＝8.0, 8.0 Hz, 1H), 7.56~7.58 (m, 3H), 7.60~7.62 (m, 1H), 8.00 (td, J＝8.0, 1.6 Hz, 1H), 8.47 (d, J＝8.0 Hz, 1H), 8.75 (d, J＝4.0 Hz, 1H), 9.03~9.06 (m, 1H), 12.23 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 60.2, 71.7, 106.7, 116.7, 117.7, 122.4, 124.0, 124.5, 125.6, 126.5, 126.6, 134.6, 136.4, 138.4, 147.9, 151.2, 155.6, 162.2; IR (film) ν: 2954, 2920, 2856, 1724, 1528, 1490, 1252 cm^－1; HRMS (ESI) calcd for C₁₈H₁₇N₂O₃ [M+H]⁺ 309.1234, found 309.1236.

  N-8-(3-Hydroxypropoxy)naphthalen-1-yl)picolinamide (3m): White solid (11 mg, 33% yield), m.p. 111~112 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 2.30~2.36 (m, 2H), 3.84 (t, J＝6.0 Hz, 2H), 4.53 (t, J＝6.0 Hz, 2H), 6.95 (d, J＝8.0 Hz, 1H), 7.34 (dd, J＝8.0, 8.0 Hz, 1H), 7.44 (d, J＝12.0 Hz, 1H), 7.46~7.48 (m, 1H), 7.50 (d, J＝8.0 Hz, 1H), 7.56 (d, J＝8.0 Hz, 1H), 7.89~7.94 (m, 1H), 8.35 (d, J＝8.0 Hz, 1H), 8.66~8.67 (m, 1H), 8.97 (d, J＝8.0 Hz, 1H), 12.65 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 31.2, 59.6, 66.3, 106.9, 117.0, 117.3, 122.1, 123.1, 124.2, 125.6, 126.3, 126.6, 134.8, 136.5, 137.8, 147.8, 151.1, 155.1, 162.6; IR (film) ν: 2948, 2917, 2845, 1660, 1524, 1491, 1271 cm^－1; HRMS (ESI) calcd for C₁₉H₁₉N₂O₃ [M+H]⁺ 323.1390, found 323.1393.

  N-(8-(4-Hydroxybutoxy)naphthalen-1-yl)picolinamide (3n): White solid (25 mg, 75% yield), m.p. 87~88 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 1.68~1.75 (m, 2H), 2.19~2.24 (m, 2H), 3.65 (t, J＝8.0 Hz, 2H), 4.35 (t, J＝8.0 Hz, 2H), 6.92 (d, J＝8.0 Hz, 1H), 7.35 (dd, J＝8.0, 8.0 Hz, 1H), 7.43~7.49 (m, 2H), 7.52 (d, J＝8.0 Hz, 1H), 7.56~7.59 (m, 1H), 7.88~7.92 (m, 1H), 8.35 (d, J＝8.0 Hz, 1H), 8.68 (d, J＝4.0 Hz, 1H), 8.98 (d, J＝8.0 Hz, 1H), 12.69 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 25.4, 29.3, 62.4, 69.6, 106.9, 117.0, 117.3, 121.9, 122.8, 124.1, 125.6, 126.2, 126.6, 134.9, 136.5, 137.5, 147.8, 151.1, 155.5, 162.7; IR (film) ν: 2962, 2929, 2868, 1671, 1527, 1495, 1238 cm^－1; HRMS (ESI) calcd for C₂₀H₂₁N₂O₃ [M+H]⁺ 337.1547, found 337.1550.

  N-(8-(3-Hydroxybutoxy)naphthalen-1-yl)picolina-mide (3o): White solid (19 mg, 57% yield), m.p. 127~128 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 1.20 (d, J＝4.0 Hz, 3H), 2.03~2.11 (m, 1H), 2.29~2.38 (m, 1H), 2.48 (s, 1H), 4.04~4.12 (m, 1H), 4.50~4.61 (m, 2H), 6.97 (d, J＝8.0 Hz, 1H), 7.35 (dd, J＝8.0, 8.0 Hz, 1H), 7.44~7.53 (m, 3H), 7.58 (d, J＝8.0 Hz, 1H), 7.90~7.94 (m, 1H), 8.37 (d, J＝8.0 Hz, 1H), 8.69 (d, J＝8.0 Hz, 1H), 9.00 (d, J＝4.0 Hz, 1H), 12.71 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 23.7, 37.5, 64.8, 66.5, 107.0, 117.0, 117.2, 122.0, 123.1, 124.1, 125.6, 126.3, 126.6, 134.9, 136.5, 137.8, 147.9, 151.1, 155.0, 162.5; IR (film) ν: 2962, 2920, 2849, 1728, 1671, 1535, 1494, 1279 cm^－1; HRMS (ESI) calcd for C₂₀H₂₁N₂O₃ [M+H]⁺ 337.1547, found 337.1549.

  N-(8-(2-(2-Hydroxyethoxy)ethoxy)naphthalen-1-yl)-picolinamide (3p): White solid (22 mg, 63% yield), m.p. 162~163 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 3.55 (t, J＝4.0 Hz, 2H), 3.62 (t, J＝4.0 Hz, 2H), 4.15 (t, J＝4.0 Hz, 2H), 4.52 (t, J＝6.0 Hz, 2H), 6.99 (d, J＝8.0 Hz, 1H), 7.37 (dd, J＝8.0, 8.0 Hz, 1H), 7.47~7.51 (m, 2H), 7.53 (d, J＝8.0 Hz, 1H), 7.58~7.60 (m, 1H), 7.91~7.96 (m, 1H), 8.38 (d, J＝4.0 Hz, 1H), 8.71 (d, J＝4.0 Hz, 1H), 8.94~8.96 (m, 1H), 12.64 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 61.8, 69.1, 69.3, 72.3, 107.9, 117.3, 117.5, 122.5, 122.9, 124.1, 125.6, 126.2, 126.7, 134.7, 136.5, 137.6, 147.7, 151.2, 155.4, 162.6; IR (film) ν: 2957, 2920, 1736, 1369, 1245, 1045 cm^－1; HRMS (ESI) calcd for C₂₀H₂₁N₂O₄ [M+H]⁺ 353.1496, found 353.1491.

  N-(8-(2-(2-(2-Hydroxyethoxy)ethoxy)ethoxy)naphtha-en-1-yl)picolinamid (3q): White solid (21 mg, 53% yield), m.p. 91~92 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 3.51~3.66 (m, 8H), 4.17 (t, J＝6.0 Hz, 2H), 4.53 (t, J＝6.0 Hz, 2H), 7.00 (d, J＝8.0 Hz, 1H), 7.37 (dd, J＝8.0, 8.0 Hz, 1H), 7.47~7.53 (m, 3H), 7.59 (d, J＝8.0 Hz, 1H), 7.94 (dd, J＝8.0, 8.0 Hz, 1H), 8.38 (d, J＝8.0 Hz, 1H), 8.72 (s, 1H), 8.96 (d, J＝8.0 Hz, 1H), 12.67 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 61.7, 69.2, 69.3, 70.4, 70.7, 72.5, 107.9, 117.2, 117.4, 122.5, 122.9, 124.1, 125.6, 126.2, 126.7, 134.7, 136.5, 137.6, 147.7, 151.2, 155.5, 162.6; IR (film) ν: 2928, 2864, 1724, 1535, 1426, 1233 cm^－1; HRMS (ESI) calcd for C₂₂H₂₅N₂O₅ [M+H]⁺ 397.1758, found 397.1761.

  N-(8-(2-Methoxyethoxy)naphthalen-1-yl)picolinamide (3r): White solid (21 mg, 65% yield), m.p. 101~102 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 3.36 (s, 3H), 4.08 (t, J＝4.0 Hz, 2H), 4.49 (t, J＝4.0 Hz, 2H), 7.00 (d, J＝8.0 Hz, 1H), 7.37 (dd, J＝8.0, 8.0 Hz, 1H), 7.48 (d, J＝8.0 Hz, 1H), 7.49~7.51 (m, 1H), 7.53 (d, J＝8.0 Hz, 1H), 7.59 (d, J＝8.0 Hz, 1H), 7.91~7.95 (m, 1H), 8.38 (d, J＝4.0 Hz, 1H), 8.72 (d, J＝8.0 Hz, 1H), 8.98 (d, J＝8.0 Hz, 1H), 12.67 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 59.0, 69.3, 70.5, 107.8, 117.2, 117.3, 122.4, 122.9, 124.0, 125.6, 126.1, 126.6, 134.8, 136.5, 137.5, 147.7, 151.2, 155.6, 162.7; IR (film) ν: 2950, 2917, 2852, 1675, 1532, 1491, 1279 cm^－1; HRMS (ESI) calcd for C₁₉H₁₉N₂O₃ [M+H]⁺ 323.1390, found 323.1393.

  N-(8-(2-Ethoxyethoxy)naphthalen-1-yl)picolinamide (3s): White solid (25 mg, 76% yield), m.p. 109~110 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 1.13(t, J＝6.0 Hz, 3H), 3.51 (q, J＝8.0 Hz, 2H), 4.10 (t, J＝6.0 Hz, 2H), 4.50 (t, J＝6.0 Hz, 2H), 7.01 (d, J＝8.0 Hz, 1H), 7.37 (dd, J＝8.0, 8.0 Hz, 1H), 7.46~7.50 (m, 2H), 7.52 (d, J＝8.0 Hz, 1H), 7.58 (d, J＝8.0 Hz, 1H), 7.91~7.95 (m, 1H), 8.37 (d, J＝8.0 Hz, 1H), 8.71 (d, J＝8.0 Hz, 1H), 8.97~8.99 (m, 1H), 12.69 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 66.7, 68.5, 69.4, 107.8, 117.2, 117.3, 122.4, 122.8, 124.0, 125.6, 126.1, 126.6, 134.8, 136.5, 137.5, 147.7, 151.2, 155.6, 162.7; IR (film) ν: 2954, 2925, 2844, 1667, 1532, 1495, 1283 cm^－1; HRMS (ESI) calcd for C₂₀H₂₁N₂O₃ [M+H]⁺ 337.1547, found 337.1539.

  N-(8-(2-(2-Methoxyethoxy)ethoxy)naphthalen-1-yl)-picolinamide (3t): White solid (24 mg, 67% yield), m.p. 77~78 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 3.33 (s, 3H), 3.46 (t, J＝4.0 Hz, 2H), 3.63 (t, J＝4.0 Hz, 2H), 4.19 (t, J＝6.0 Hz, 2H), 4.54 (t, J＝6.0 Hz, 2H), 7.01 (d, J＝8.0 Hz, 1H), 7.37 (dd, J＝8.0, 8.0 Hz, 1H), 7.46~7.53 (m, 3H), 7.58 (d, J＝8.0 Hz, 1H), 7.91~7.95 (m, 1H), 8.37 (d, J＝8.0 Hz, 1H), 8.73 (d, J＝4.0 Hz, 1H), 8.98 (d, J＝8.0 Hz, 1H), 12.69 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 59.1, 69.3, 70.6, 71.9, 107.8, 117.2, 117.3, 122.4, 122.8, 124.0, 125.6, 126.1, 126.6, 134.8, 136.5, 137.5, 147.8, 151.2, 155.5, 162.6; IR (film) ν: 2917, 2868, 1679, 1456, 1350, 1200 cm^－1; HRMS (ESI) calcd for C₂₁H₂₃N₂O₄ [M+H]⁺, 367.1652, found 367.1658.

  N-(8-Methoxynaphthalen-1-yl)picolinamide (3a'): Light yellow solid (14 mg, 50% yield), m.p. 176~177 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 6.92~6.94 (m, 1H), 7.39 (dd, J＝8.0, 8.0 Hz, 1H), 7.46~7.52 (m, 2H), 7.53 (d, J＝8.0 Hz, 1H), 7.57~7.59 (m, 1H), 7.91~7.96 (m, 1H), 8.35~8.38 (m, 1H), 8.72~8.73 (m, 1H), 8.99~9.02 (m, 1H), 13.25 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 105.7, 116.6 (2C), 121.9, 122.6, 123.7, 125.6, 126.1, 126.8, 135.2, 136.4, 137.5, 148.0, 151.2, 156.2, 162.4; IR (film) ν: 2949, 2921, 2851, 1679, 1544, 1491, 1290 cm^－1; HRMS (ESI) calcd for C₁₇H₁₂D₃N₂O₂ [M+H]⁺ 282.1316, found 282.1320.

  N-(5-Bromo-8-butoxynaphthalen-1-yl)picolinamide (3w): White solid (13 mg, 32% yield), m.p. 153~155 ℃; ¹H NMR (400 Hz, CDCl₃, TMS) δ: 0.94 (t, J＝8.0 Hz, 3H), 1.44~1.53 (m, 2H), 2.07~2.15 (m, 2H), 4.34 (t, J＝6.0 Hz, 2H), 6.82 (d, J＝8.0 Hz, 1H), 7.50~7.54 (m, 1H), 7.63~7.70 (m, 2H), 7.93~7.97 (m, 1H), 8.05~8.07 (m, 1H), 8.38 (d, J＝8.0 Hz, 1H), 8.69 (d, J＝4.0 Hz, 1H), 9.06~9.08 (m, 1H), 12.73 (s, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 13.8, 19.3, 30.8, 70.0, 107.2, 114.8, 118.2, 118.3, 122.9, 123.3, 126.2, 128.0, 129.7, 134.0, 135.3, 137.5, 147.7, 151.0, 155.6, 162.8; IR (film) ν: 2958, 2921, 2846, 1667, 1524, 1491, 1389 cm^－1; HRMS (ESI) calcd for C₂₀H₂₀BrN₂O₂ [M+H]⁺ 399.0703, found 399.0705.

  8-Butoxynaphthalen-1-amine (4): Green liquid (20 mg, 93% yield); ¹H NMR (400 Hz, CDCl₃, TMS) δ: 1.01 (t, J＝8.0 Hz, 3H), 1.51~1.61 (m, 2H), 1.87~1.94 (m, 2H), 4.11 (t, J＝8.0 Hz, 2H), 6.57 (d, J＝4.0 Hz, 1H), 6.68 (d, J＝4.0 Hz, 1H), 7.10 (d, J＝8.0 Hz, 1H), 7.18~7.25 (m, 2H), 7.30 (d, J＝8.0 Hz, 1H); ¹³C NMR (100 Hz, CDCl₃, TMS) δ: 13.9, 19.5, 31.3, 68.5, 104.3, 109.6, 115.1, 116.9, 121.2, 125.6, 127.0, 137.3, 145.0, 157.2; IR (film) ν: 3052, 2962, 2864, 1593, 1401, 1299, 1242 cm^－1; HRMS (ESI) calcd for C₁₄H₁₈NO [M+H]⁺ 216.1383, found 216.1380.

  Supporting Information UV, ¹H NMR, ¹³C NMR spectra of compounds 3~4. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn/.

  
  
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• 

  Scheme 1  Preparation of deuterium labeled methoxylated 1-naphthylamide

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  Scheme 2  Reaction scope of 1-naphthylamine derivatives

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  Scheme 3  Removal the directing group

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  Table 1.  Optimization of the reaction conditions^a

  Entry	Cat.	Oxidant	Base	Additive	Yieldb/%
  1	Co(OAc)2	Ag2CO3	KOAc	—	32
  2	CoCl2	Ag2CO3	KOAc	—	12
  3	Co2(CO)8	Ag2CO3	KOAc	—	21
  4	Co(acac)2	Ag2CO3	KOAc	—	NR
  5	Pd(OAc)2	Ag2CO3	KOAc	—	NR
  6	Co(OAc)2	Ag2O	KOAc	—	40
  7	Co(OAc)2	AgOAc	KOAc	—	20
  8	Co(OAc)2	AgOTFA	KOAc	—	23
  9	Co(OAc)2	Mn(OAc)2•2H2O	KOAc	—	17
  10	Co(OAc)2	Mn(OAc)2	KOAc	—	61
  11	Co(OAc)2	Mn(OAc)2	Na2CO3	—	25
  12	Co(OAc)2	Mn(OAc)2	K2CO3	—	28
  13	Co(OAc)2	Mn(OAc)2	Cs2CO3	—	30
  14	Co(OAc)2	Mn(OAc)2	KOAc	—	43c
  15	—	Mn(OAc)2	KOAc	—	0
  16	Co(OAc)2	—	KOAc	—	0
  17	Co(OAc)2	Mn(OAc)2	KOAc	n-Bu4NI	13
  18	Co(OAc)2	Mn(OAc)2	KOAc	n-Bu4NOAc	21
  19	Co(OAc)2	Mn(OAc)2	KOAc	n-Bu4NPF6	26
  20	Co(OAc)2	Mn(OAc)2	KOAc	18-Crown-6	38
  21	Co(OAc)2	Mn(OAc)2	KOAc	—	19d
  22	Co(OAc)2	Mn(OAc)2	KOAc	—	21e
  23	Co(OAc)2	Mn(OAc)2	KOAc	—	44 f
  24	Co(OAc)2	Mn(OAc)2	KOAc	—	13 g
  a Reaction conditions unless otherwise specified: 1 (0.1 mmol), catalyst (30 mol%), oxidant (2.0 equiv.), base (2.0 equiv.), additive (2.0 equiv.), MeOH (1 mL), 80 ℃ under air for 12 h. b Isolated yield. c The amount of KOAc was increased to 10 equiv. d Used toluene as the solvent and the volume ratio of MeOH and toluene was 1:1 (1.0 mL). e Used O-chlorotoluene as the solvent and the volume ratio of MeOH and O-chlorotoluene was 1:1 (1.0 mL). f The amount of Co(OAc)2 was reduced to 20 mol%. g The amount of Co(OAc)2 was reduced to 10 mol%.

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  Table 2.  Cobalt-catalyzed alkoxylation of 1-naphthylamine derivative with various alcohols^a

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•