Microwave-Assisted Cyclization under Mildly Basic Conditions

Mar 22, 2018 - Microwave-Assisted Cyclization under Mildly Basic Conditions: Synthesis of 6H‑Benzo[c]chromen-6-ones and Their 7,8,9,10-. Tetrahydro ...
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Note Cite This: J. Org. Chem. 2018, 83, 4140−4146

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Microwave-Assisted Cyclization under Mildly Basic Conditions: Synthesis of 6H‑Benzo[c]chromen-6-ones and Their 7,8,9,10Tetrahydro Analogues Pham Duy Quang Dao,† Son Long Ho,† Ho-Jin Lim,‡ and Chan Sik Cho*,† †

Department of Applied Chemistry, Kyungpook National University, 80 Daehakro, Bukgu, Daegu 41566, Republic of Korea Department of Environmental Engineering, Kyungpook National University, 80 Daehakro, Bukgu, Daegu 41566, Republic of Korea

‡

S Supporting Information *

ABSTRACT: Aryl 2-bromobenzoates and aryl 2-bromocyclohex-1-enecarboxylates are cyclized by microwave irradiation in dimethylformamide in the presence of K2CO3 to give the corresponding 6H-benzo[c]chromen-6-ones and their 7,8,9,10-tetrahydro analogues, respectively, in 50−72% yields. Aryl 3bromoacrylates are also converted into 2H-chromen-2-ones under the employed conditions.

I

synthesized by palladium-catalyzed intramolecular biaryl coupling of aryl 2-halobenzoates (Scheme 1, route i).12 Besides the above-mentioned synthetic methods, multicomponent and multistep protocols to construct such scaffolds also have been developed.13 These precedents, even though showing their individual advantages, have some drawbacks such as requiring expensive consumable transition metals to synthesize starting materials and products, contamination of residual metals in starting materials and products, tedious procedures, and using hazardous carbon monoxide gas. During the course of our continuing studies directed toward developing novel and efficient synthetic methods for heterocycles,14 this report describes transition metal-free microwave-assisted lactonization of aryl 2-bromobenzoates in the presence of a weak base leading to 6H-benzo[c]chromen-6-ones. Treatment of phenyl 2-bromobenzoate (1a) in dimethylformamide at 120 °C for 0.5 h in the presence of K2CO3 (5 equiv) under microwave irradiation (100 W of initial power) afforded 6H-benzo[c]chromen-6-one (2a) in 19% yield with an incomplete conversion of 1a (Table 1, entry 1). The yield of 2a increases on prolonging the reaction time up to 2 h; however, the starting 1a still remained (Table 1, entries 2−4). A higher reaction temperature did not affect the yield of 2a (Table 1, entry 5). Performing the reaction under the increased amount of K2CO3 up to 10 equiv to 1a resulted in a considerably increased yield of 2a along with complete conversion of 1a (Table 1, entries 6 and 7).15 It is unclear why such a large excess of base is needed for the effective formation of 2a. Here again, a lower yield along with incomplete conversion of 1a was observed under a shorter reaction time (Table 1, entry 8). The reaction also proceeded with other bases such as K3PO4 and Cs2CO3, but the yields of 2a were generally lower than those obtained in the presence of

t is known that many naturally occurring 6H-benzo[c]chromen-6-ones exhibit diverse biological activities.1,2 Thus, many synthetic methods have been developed and documented for such 6H-benzo[c]chromen-6-ones due to limited quantities of natural sources.1 It is reported that such a scaffold can be synthesized by copper(I) thiophene carboxylate (CuTC)mediated lactonization of 2′-halobiphenyl-2-carboxylic acids and Lewis acid-mediated lactonization of 2′-methoxybiphenyl2-carboxylic acids and methyl 2′-methoxybiphenyl-2-carboxylates (Scheme 1, route a).3,4 Deng et al. also demonstrated palladium/copper-catalyzed decarboxylative coupling and cyclization of 2-nitrobenzoic acids with methyl 2-halobenzoates leading to 6H-benzo[c]chromen-6-ones (Scheme 1, route b).5 A similar reaction is also exemplified by the palladium-catalyzed Suzuki−Miyaura cross-coupling of 2-halobenzaldehydes and methyl 2-halobenzoates with 2-hydroxyarylboronic acids followed by lactonization (Scheme 1, route c).6 Several groups also have shown that 2-arylbenzoic acids can be converted into 6H-benzo[c]chromen-6-ones by carboxyl-directed C−H activation/C−O cyclization in the presence of catalysts such as Pd, Cu, Ag, and iodine reagents as well as photocatalyst 9-mesityl10-methylacridinium perchlorate combined with (NH4)2S2O8 (Scheme 1, route d).7 Ray and co-workers reported that 2arylbenzaldehydes undergo aryl C−H oxidative lactonization in the presence of CuCl as a catalyst and tert-butyl hydroperoxide (TBHP) as an oxidant to afford 6H-benzo[c]chromen-6-ones (Scheme 1, route e).8 Such a similar lactonization through C− H activation was also shown by palladium- and rutheniumcatalyzed carbonylation and cyclization (carbonylative cyclization) of 2-arylphenols leading to 6H-benzo[c]chromen-6-ones (Scheme 1, route f).9 Palladium-catalyzed direct oxidative coupling and annulation of benzoic acids with phenols were also reported to construct 6H-benzo[c]chromen-6-ones (Scheme 1, route g).10 A classical Baeyer−Villiger oxidation of 9-fluorenone also gives 6H-benzo[c]chromen-6-one (Scheme 1, route h).11 In connection with these reports, it is also reported that 6H-benzo[c]chromen-6-ones can be © 2018 American Chemical Society

Received: January 8, 2018 Published: March 22, 2018 4140

DOI: 10.1021/acs.joc.8b00048 J. Org. Chem. 2018, 83, 4140−4146

Note

The Journal of Organic Chemistry Scheme 1. Various Synthetic Methods for 6H-Benzo[c]chromen-6-ones

Table 1. Optimization of Conditions for the Reaction of 1aa

entry

base (mmol)

temp (°C)

time (h)

yieldb (%)

1 2 3 4 5 6 7 8 9 10 11 12 13c 14d 15d,e

K2CO3 (1.5) K2CO3 (1.5) K2CO3 (1.5) K2CO3 (1.5) K2CO3 (1.5) K2CO3 (2.1) K2CO3 (3) K2CO3 (3) K3PO4 (3) Cs2CO3 (3) NaOtBu (3)

120 120 120 120 150 120 120 120 120 120 120 120 120 120 120

0.5 1 2 3 2 2 2 0.5 2 2 2 2 24 2 2

19 26 45 46 45 52 64 39 28 31 0 0 15 63 57

K2CO3 (3) K2CO3 (3) K2CO3 (3)

treatment of phenyl 2-iodobenzoate under the employed conditions afforded 2a in similar yields irrespective of the addition of N,N′-dimethylethylenediamine (DMEDA) (Table 1, entries 14 and 15). Various aryl 2-bromobenzoates 1a−k were subjected to the reaction under the optimized reaction conditions in order to investigate the scope of the reaction, and several representative results are summarized in Table 2. Performing the reaction with aryl 2-bromobenzoates 1b−g having electron-donating and -withdrawing substituents on O-attached aryl groups afforded the corresponding 6H-benzo[c]chromen-6-ones 2b−g in 51− 68% yields without identifiable byproducts by ester hydrolysis.18 The product yield was not significantly affected by the position of the substituent, whereas the electronic nature of that had a somewhat relevance to the product yield. Lower reaction rates and yields were observed with 1c and 1f, having an electron-donating methoxy group. With meta-substituted aryl 2bromobenzoate 1h, the corresponding product was obtained as regioisomers (2h and 2h′) in a similar yield, favoring the cyclization of a less sterically hindered position.19 The cyclization of benzo-fused and methoxy-substituted phenyl 2bromobenzoates (1i and 1j) also proceeded to give the corresponding 6H-benzo[c]chromen-6-ones (2i and 2j) in similar yields. Treatment of phenyl 2-bromopyridine-3carboxylate (1k) under the employed conditions also afforded 5H-chromeno[4,3-b]pyridin-5-one (2k) in 60% yield. The present protocol can be extended to the reaction with aryl 2bromocyclohex-1-enecarboxylates 1l−t (Table 2). A similar treatment of phenyl 2-bromocyclohex-1-enecarboxylate (1l) under the same conditions afforded 7,8,9,10-tetrahydro-6Hbenzo[c]chromen-6-one (2l) in 72% yield. Phenyl 2bromocyclohex-1-enecarboxylates (1m and 1n) having methyl and phenyl substituents on a cyclohexene ring were also cyclized to give the corresponding 7,8,9,10-tetrahydro-6Hbenzo[c]chromen-6-ones (2m and 2n) in similar yields, irrespective of such substituents. Aryl 2-bromocyclohex-1enecarboxylates 1o−q having methyl and chloro substituents

a

Reaction conditions: 1a (0.3 mmol), DMF (3 mL), under microwave irradiation (100 W of initial power) and N2, unless otherwise stated. b Isolated yield. cUnder usual heating (screw-capped vial). dPhenyl 2iodobenzoate was used in place of 1a. eN,N′-Dimethylethylenediamine (0.06 mmol) was further added.

K2CO3 (Table 1, entries 9 and 10). However, the reaction did not proceed at all in the presence of NaOtBu or in the absence of a base, and the starting 1a was recovered almost completely (Table 1, entries 11 and 12).16 Treatment of 1a under the usual heating method (screw-capped vial, 120 °C for 24 h) afforded 2a in only 15% yield (Table 1, entry 13). It is known that transition metal-free cross-coupling of aryl iodides with arenes was accelerated by the addition of a diamine ligand.17 However, 4141

DOI: 10.1021/acs.joc.8b00048 J. Org. Chem. 2018, 83, 4140−4146

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The Journal of Organic Chemistry Table 2. Scope of Cyclization Reactiona

a

Reaction conditions: 1 (0.3 mmol), K2CO3 (3 mmol), DMF (3 mL), 120 °C, 2 h, under microwave irradiation (100 W initial power) and N2.

starting 1s prior to cyclization also could not be excluded. Such a similar dehydrogenation was observed by our recent reports on copper-catalyzed coupling and cyclization reactions.14a,21 It is known that 7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-ones, analogues of 6H-benzo[c]chromen-6-ones, exhibit biological activities such as cholinesterase inhibitors, atypical antipsychotics, and steroid sulfatase inhibitors.22 A similar treatment of phenyl 3-bromoacrylates (1u and 1v) under the employed conditions also afforded 2H-chromen-2-ones (2t and 2u); however, the product yield was lower than that when previously described aryl 2-bromobenzoates and aryl 2-bromocyclohex-1enecarboxylates were used. A variety of synthetic methods and

on aryl groups also afforded the corresponding 7,8,9,10tetrahydro-6H-benzo[c]chromen-6-ones 2o−q in 65−69% yields. As is the case for the reaction with 1h, the cyclization of m-tolyl 2-bromocyclohex-1-enecarboxylate (1r) proceeded with a similar regioselective pattern.19 For testing the effect of the position of bromide and carbophenoxy groups on benzofused phenyl 2-bromocyclohex-1-enecarboxylates, 1s and 1t were employed. Even though the cyclization took place irrespective of the position, in the reaction with 1s, 2i was formed by dehydrogenation of 11,12-dihydronaphtho[1,2c]chromen-5-one initially formed by the cyclization of 1s under the employed conditions.20 Dehydrogenation of the 4142

DOI: 10.1021/acs.joc.8b00048 J. Org. Chem. 2018, 83, 4140−4146

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The Journal of Organic Chemistry Scheme 2. Reaction Pathway

Intermediate radical 3 triggers preferential 6-exo/endo-trig radical cyclization to produce a cyclohexadienyl radical 4, which is deprotonated by K2CO3 to form an anionic radical 5. This is followed by transfer of an electron to the starting material to give product 6 along with radical 3 and KBr (Scheme 2, route a). An alternative initial 5-exo-trig ipso cyclization to form a spirocyclohexadienyl radical 7 followed by a concerted ring expansion and subsequent deprotonation and radical chain transfer produces isomer 10 (Scheme 2, route b). However, no isomer 10 was detected from the reaction with

a fascinating array of pharmacological properties for 2Hchromen-2-one (coumarin)-containing compounds are welldocumented.23 The reaction with benzyl 2-bromobenzoate under the employed conditions did not proceed at all toward cyclization, and the starting material was recovered almost completely (96%). Based on several similar precedents,24 the reaction pathway seems to proceed via an initial K2CO3-induced generation of an aryl radical 3 from para-substituted 1 by single-electron transfer prior to homolytic aromatic substitution (Scheme 2). 4143

DOI: 10.1021/acs.joc.8b00048 J. Org. Chem. 2018, 83, 4140−4146

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The Journal of Organic Chemistry

NMR (125 MHz, CDCl3): δ 55.8, 106.3, 117.1, 118.5, 118.6, 121.3, 121.7, 128.9, 130.6, 134.6, 134.7, 145.6, 156.3, 161.3. 2-Chloro-6H-benzo[c]chromen-6-one (2d).5 Rf = 0.45. White solid (47 mg, 68%). Mp 180−181 °C. 1H NMR (500 MHz, CDCl3): δ 7.31 (d, J = 8.8 Hz, 1H), 7.43 (dd, J = 8.8 and 2.4 Hz, 1H), 7.62−7.65 (m, 1H), 8.01 (d, J = 2.4 Hz, 1H), 8.06 (d, J = 8.1 Hz, 1H), 8.41 (dd, J = 8.0 and 1.0 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 119.2, 119.4, 121.3, 121.8, 122.6, 129.6, 130.1, 130.4, 130.8, 133.6, 135.1, 149.7, 160.6. 4-Methyl-6H-benzo[c]chromen-6-one (2e).5 Rf = 0.48. White solid (38 mg, 61%). Mp 120−122 °C. 1H NMR (500 MHz, CDCl3): δ 2.49 (s, 3H), 7.22 (t, J = 7.7 Hz, 1H), 7.31−7.33 (m, 1H), 7.55−7.58 (m, 1H), 7.79−7.82 (m, 1H), 7.88−7.90 (m, 1H), 8.10 (d, J = 8.1 Hz, 1H), 8.39−8.41 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 16.0, 117.7, 120.4, 121.1, 121.9, 124.0, 127.0, 128.6, 130.5, 131.8, 134.7, 135.1, 149.6, 161.2. 4-Methoxy-6H-benzo[c]chromen-6-one (2f). Rf = 0.30. White solid (37 mg, 54%). Mp 134−136 °C. 1H NMR (500 MHz, CDCl3): δ 3.99 (s, 3H), 7.05 (dd, J = 8.1 and 1.2 Hz, 1H), 7.26−7.29 (m, 1H), 7.58−7.61 (m, 1H), 7.65 (dd, J = 8.2 and 1.1 Hz, 1H), 7.81−7.85 (m, 1H), 8.12 (d, J = 8.1 Hz, 1H), 8.42−8.44 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 56.3, 112.2, 114.2, 118.8, 121.3, 122.2, 124.2, 129.0, 130.6, 134.8, 135.0, 141.1, 148.1, 160.6. HRMS (EI): calcd for C14H10O3 (M+), 226.0630; found, 226.0627. 4-Chloro-6H-benzo[c]chromen-6-one (2g). Rf = 0.35. White solid (45 mg, 65%). Mp 144−146 °C. 1H NMR (500 MHz, CDCl3): δ 7.28 (t, J = 8.0 Hz, 1H), 7.55 (dd, J = 7.9 and 1.4 Hz, 1H), 7.61−7.64 (m, 1H), 7.84−7.87 (m, 1H), 7.97 (dd, J = 8.1 and 1.3 Hz, 1H), 8.12 (d, J = 8.1 Hz, 1H), 8.42 (dd, J = 8.0 and 1.0 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 119.6, 121.1, 121.2, 122.0, 122.7, 124.5, 129.5, 130.7, 130.9, 134.2, 135.1, 147.1, 160.0. HRMS (EI): calcd for C13H7ClO2 (M+), 230.0135; found, 230.0132. 3-Methyl-6H-benzo[c]chromen-6-one (2h).7a Rf = 0.43. White solid (21 mg, 33%). Mp 124−125 °C. 1H NMR (500 MHz, CDCl3): δ 2.46 (s, 3H), 7.16−7.18 (m, 1H), 7.19 (s, 1H), 7.56−7.58 (m, 1H), 7.80−7.82 (m, 1H), 7.95 (d, J = 8.1 Hz, 1H), 8.10 (d, J = 8.1 Hz, 1H), 8.40 (dd, J = 7.9 and 1.0 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 21.5, 115.5, 117.9, 120.9, 121.5, 122.5, 125.7, 128.4, 130.6, 134.8, 135.0, 141.3, 151.3, 161.5. 1-Methyl-6H-benzo[c]chromen-6-one (2h′).7e Rf = 0.43. White solid (17 mg, 26%). Mp 176−178 °C. 1H NMR (500 MHz, CDCl3): δ 2.91 (s, 3H), 7.18−7.19 (m, 1H), 7.28−7.30 (m, 1H), 7.35−7.39 (m, 1H), 7.59−7.63 (m, 1H), 7.83−7.86 (m, 1H), 8.41 (d, J = 8.4 Hz, 1H), 8.51 (dd, J = 7.9 and 1.4 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 25.6, 116.3, 117.6, 122.2, 126.2, 128.1, 128.9, 129.3, 130.9, 134.3, 136.1, 136.2, 152.3, 161.3. 5H-Naphtho[1,2-c]chromen-5-one (2i).6b Rf = 0.40. White solid (49 mg, 67%). Mp 188−189 °C. 1H NMR (500 MHz, CDCl3): δ 7.35−7.39 (m, 1H), 7.41−7.43 (m, 1H), 7.51−7.55 (m, 1H), 7.61− 7.65 (m, 1H), 7.75−7.78 (m, 1H), 7.90−7.92 (m, 1H), 8.15−8.18 (m, 2H), 8.22 (d, J = 8.8 Hz, 1H), 9.80 (d, J = 8.3 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 115.2, 117.2, 118.2, 118.8, 123.5, 124.3, 127.2, 127.3, 128.7, 129.6, 130.8, 132.1, 133.3, 136.5, 136.7, 151.7, 160.4. 8-Methoxy-6H-benzo[c]chromen-6-one (2j).5 Rf = 0.37. White solid (47 mg, 70%). Mp 152−153 °C. 1H NMR (500 MHz, CDCl3): δ 3.94 (s, 3H), 7.31−7.37 (m, 2H), 7.39−7.45 (m, 2H), 7.82 (d, J = 2.8 Hz, 1H), 7.99 (dd, J = 7.9 and 1.5 Hz, 1H), 8.04 (d, J = 8.9 Hz, 1H). 13 C NMR (125 MHz, CDCl3): δ 55.8, 111.2, 117.6, 118.2, 122.2, 122.5, 123.4, 124.3, 124.6, 128.2, 129.3, 150.5, 160.1, 161.3. 5H-Chromeno[4,3-b]pyridin-5-one (2k).6a,26 Rf = 0.38. White solid (45 mg, 60%). Mp 165−166 °C. 1H NMR (500 MHz, CDCl3): δ 7.25−7.29 (m, 1H), 7.36−7.39 (m, 2H), 7.51−7.54 (m, 1H), 7.73 (dd, J = 7.7 and 2.0 Hz, 1H), 7.96 (d, J = 8.1 Hz, 1H), 8.43−8.44 (m, 1H). 13 C NMR (125 MHz, CDCl3): δ 118.6, 118.8, 122.0, 122.5, 123.5, 125.3, 129.7, 131.2, 131.3, 135.6, 152.1, 161.9. 7,8,9,10-Tetrahydro-6H-benzo[c]chromen-6-one (2l).7d Rf = 0.37. White solid (44 mg, 72%). Mp 117−119 °C. 1H NMR (500 MHz, CDCl3): δ 1.79−1.90 (m, 4H), 2.58−2.61 (m, 2H), 2.78−2.80 (m, 2H), 7.25−7.29 (m, 1H), 7.31 (dd, J = 8.3 and 0.9 Hz, 1H), 7.44−7.47 (m, 1H), 7.56 (dd, J = 7.9 and 1.3 Hz, 1H). 13C NMR (125 MHz,

para-substituted 1. The reaction pathways for ortho- and metasubstituted 1, consistent with the products formed, are also shown in Scheme 2. Intermediate radicals A and B initially formed by such single-electron transfer are also preferentially cyclized in a 6-exo/endo-trig fashion to give the corresponding products. We confirmed in a separate experiment that the reaction of 1a under the condition of entry 7 of Table 1 with a further addition of the radical scavenger, 2,6-di-tert-butyl-4methylphenol, TEMPO or galvinoxyl (equimolar amount to 1a) caused the cyclization to slow down (5−9% yield of 2a). These results indicate that the present reaction seems to proceed via the radical pathway. In conclusion, it has been shown that aryl 2-bromobenzoates, aryl 2-bromocyclohex-1-enecarboxylates, and phenyl 3-bromoacrylates trigger lactonization under microwave irradiation in the presence of potassium carbonate to form the corresponding 6H-benzo[c]chromen-6-ones and their 7,8,9,10-tetrahydro analogues and 2H-chromen-2-ones, respectively. The present reaction provides an environmentally benign synthetic method for such scaffolds from readily available starting compounds compared with known protocols. A further divergent synthetic application for heterocycles using such metal-free microwaveassisted cyclization is currently under investigation.

■

EXPERIMENTAL SECTION

General Information. 1H and 13C NMR spectra were recorded at 500 and 125 MHz, respectively, in CDCl3. Melting points were determined on a microscopic melting point apparatus. High-resolution mass data were recorded using electronic ionization (HRMS-EI, magnetic sector-electric sector double focusing mass analyzer) at the Korea Basic Science Center, Daegu, Korea. All microwave reactions (CEM, Discover LabMate) were carried out in a sealed tube (5 mL), and maintenance of the reaction temperature was monitored by an external infrared sensor. The isolation of pure products was carried out via thin-layer (a glass plate coated with Kieselgel 60 GF254, Merck) chromatography. All starting esters were prepared by a one-pot initial conversion of the corresponding carboxylic acids to acid chlorides using thionyl chloride followed by treatment with phenols.12e All other reagents were purchased from commercial sources and used without further purification. General Procedure for the Synthesis of 2. A 5 mL microwave reaction tube was charged with 1 (0.3 mmol) with K2CO3 (0.415 g, 3.0 mmol) and DMF (3 mL). After the tube was flushed with N2 and capped, the reaction mixture was heated to 120 °C for 2 h by microwave irradiation at 100 W of initial power. The mixture was then cooled to room temperature and filtered through a short silica gel column (ethyl acetate) to remove inorganic components. Removal of the solvent left a crude mixture, which was separated by TLC (hexane/ ethyl acetate = 10/1) to give 2. All products were characterized spectroscopically as shown below. 6H-Benzo[c]chromen-6-one (2a).7d Rf = 0.42. White solid (38 mg, 64%). Mp 93−94 °C. 1H NMR (500 MHz, CDCl3): δ 7.32−7.37 (m, 2H), 7.46−7.50 (m, 1H), 7.57−7.60 (m, 1H), 7.81−7.84 (m, 1H), 8.06 (dd, J = 8.0 and 1.5 Hz, 1H), 8.12 (d, J = 8.1 Hz, 1H), 8.39−8.41 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 117.8, 118.0, 121.3, 121.7, 122.8, 124.5, 128.9, 130.4, 130.6, 134.7, 134.8, 151.3, 161.2. 2-Methyl-6H-benzo[c]chromen-6-one (2b).5,25 Rf = 0.40. White solid (36 mg, 57%). Mp 121−123 °C. 1H NMR (500 MHz, CDCl3): δ 2.45 (s, 3H), 7.22−7.27 (m, 2H), 7.54−7.57 (m, 1H), 7.78−7.84 (m, 2H), 8.08 (d, J = 8.1 Hz, 1H), 8.38 (dd, J = 8.0 and 1.0 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 21.1, 117.5, 117.6, 121.3, 121.6, 122.7, 128.7, 130.5, 131.3, 134.1, 134.7, 134.8, 149.3, 161.3. 2-Methoxy-6H-benzo[c]chromen-6-one (2c).5 Rf = 0.27. White solid (35 mg, 51%). Mp 118−120 °C. 1H NMR (500 MHz, CDCl3): δ 3.90 (s, 3H), 7.03 (dd, J = 9.0 and 2.9 Hz, 1H), 7.27 (d, J = 9.0 Hz, 1H), 7.45 (d, J = 2.9 Hz, 1H), 7.55−7.59 (m, 1H), 7.79−7.82 (m, 1H), 8.03 (d, J = 8.1 Hz, 1H), 8.38 (dd, J = 8.0 and 1.0 Hz, 1H). 13C 4144

DOI: 10.1021/acs.joc.8b00048 J. Org. Chem. 2018, 83, 4140−4146

Note

The Journal of Organic Chemistry CDCl3): δ 21.4, 21.6, 24.1, 25.2, 116.7, 120.2, 123.1, 123.8, 124.0, 130.2, 147.0, 152.0, 161.7. 8-Methyl-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one (2m). Rf = 0.47. White solid (43 mg, 67%). Mp 104−106 °C. 1H NMR (500 MHz, CDCl3): δ 1.12 (d, J = 6.6 Hz, 3H), 1.39−1.47 (m, 1H), 1.78−1.88 (m, 1H), 1.98−2.03 (m, 1H), 2.07−2.14 (m, 1H), 2.70− 2.84 (m, 2H), 2.93−2.97 (m, 1H), 7.26−7.29 (m, 1H), 7.32 (dd, J = 8.2 and 1.0 Hz, 1H), 7.44−7.48 (m, 1H), 7.57 (dd, J = 8.0 and 1.4 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 21.3, 25.3, 27.9, 29.4, 32.3, 116.8, 120.1, 123.3, 123.4, 124.0, 130.3, 146.7, 152.0, 161.8. HRMS (EI): calcd for C14H14O2 (M+), 214.0994; found, 214.0996. 8-Phenyl-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one (2n). Rf = 0.38. White solid (52 mg, 62%). Mp 122−123 °C. 1H NMR (500 MHz, CDCl3): δ 1.84−1.93 (m, 1H), 2.17−2.23 (m, 1H), 2.52− 2.59 (m, 1H), 2.77−2.83 (m, 1H), 2.85−2.90 (m, 1H), 2.92−3.02 (m, 2H), 7.16−7.19 (m, 1H), 7.20−7.24 (m, 3H), 7.25−7.28 (m, 3H), 7.40−7.43 (m, 1H), 7.52 (dd, J = 7.9 and 1.3 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 25.9, 28.6, 31.7, 39.2, 117.0, 120.1, 123.4, 123.5, 124.2, 126.7, 126.9, 128.7, 130.6, 145.1, 146.8, 152.2, 161.6. HRMS (EI): calcd for C19H16O2 (M+), 276.1150; found, 276.1151. 2-Methyl-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one (2o).27 Rf = 0.33. White solid (42 mg, 65%). Mp 136−138 °C. 1H NMR (500 MHz, CDCl3): δ 1.70−1.81 (m, 4H), 2.33 (s, 3H), 2.49−2.52 (m, 2H), 2.68−2.71 (m, 2H), 7.11 (d, J = 8.4 Hz, 1H), 7.17 (dd, J = 8.4 and 1.6 Hz, 1H), 7.26 (s, 1H). 13C NMR (125 MHz, CDCl3): δ 21.1, 21.4, 21.6, 24.1, 25.2, 116.4, 119.9, 123.1, 123.6, 131.2, 133.5, 146.9, 150.1, 162.0. 2-Chloro-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one (2p). Rf = 0.38. White solid (48 mg, 69%). Mp 132−134 °C. 1H NMR (500 MHz, CDCl3): δ 1.80−1.91 (m, 4H), 2.59−2.61 (m, 2H), 2.74−2.76 (m, 2H), 7.26 (d, J = 8.1 Hz, 1H), 7.41 (dd, J = 8.8 and 2.3 Hz, 1H), 7.53 (d, J = 2.3 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 21.2, 21.4, 24.2, 25.1, 118.1, 121.4, 122.9, 125.1, 129.5, 130.2, 146.0, 150.4, 161.2. HRMS (EI): calcd for C13H11ClO2 (M+), 234.0448; found, 234.0445. 4-Methyl-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one (2q). Rf = 0.42. White solid (45 mg, 69%). Mp 107−108 °C. 1H NMR (500 MHz, CDCl3): δ 1.73−1.82 (m, 4H), 2.38 (s, 3H), 2.51−2.54 (m, 2H), 2.70−2.73 (m, 2H), 7.09 (t, J = 7.7 Hz, 1H), 7.23 (d, J = 7.3 Hz, 1H), 7.33 (d, J = 7.9 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 15.7, 21.5, 21.6, 24.1, 25.3, 119.9, 120.8, 123.4, 123.5, 126.0, 131.6, 147.3, 150.4, 161.9. HRMS (EI): calcd for C14H14O2 (M+), 214.0994; found, 214.0994. 3-Methyl-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one (2r).27 Rf = 0.37. White solid (21 mg, 32%). Mp 109−110 °C. 1H NMR (500 MHz, CDCl3): δ 1.78−1.89 (m, 4H), 2.43 (s, 3H), 2.57−2.60 (m, 2H), 2.76−2.79 (m, 2H), 7.08 (dd, J = 8.1 and 1.0 Hz, 1H), 7.12 (s, 1H), 7.44 (d, J = 8.1 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 21.4, 21.5, 21.7, 24.0, 25.2, 116.9, 117.8, 122.6, 122.9, 125.1, 141.1, 147.1, 152.1, 162.1. 1-Methyl-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one (2r′). Rf = 0.37. White solid (17 mg, 26%). Mp 164−166 °C. 1H NMR (500 MHz, CDCl3): δ 1.77−1.82 (m, 4H), 2.61−2.63 (m, 2H), 2.72 (s, 3H), 2.99−3.02 (m, 2H), 7.03 (dd, J = 7.5 and 0.6 Hz, 1H), 7.17 (dd, J = 8.2 and 0.8 Hz, 1H), 7.26−7.30 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 20.9, 22.5, 25.0, 25.2, 30.9, 115.7, 120.1, 124.0, 128.6, 129.4, 135.8, 149.7, 153.0, 161.4. HRMS (EI): calcd for C14H14O2 (M+), 214.0994; found, 214.0996. 7,8-Dihydro-6H-naphtho[2,1-c]chromen-6-one (2s).28 Rf = 0.47. Viscous oil (45 mg, 61%). 1H NMR (500 MHz, CDCl3): δ 2.75−2.78 (m, 2H), 2.82−2.85 (m, 2H), 7.28−7.32 (m, 1H), 7.36−7.43 (m, 4H), 7.50−7.53 (m, 1H), 7.83 (d, J = 7.7 Hz, 1H), 8.04 (dd, J = 8.1 and 1.4 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 22.2, 28.1, 117.5, 117.6, 123.9, 124.2, 126.3, 126.4, 128.0, 128.5, 130.1, 130.3, 130.5, 140.1, 144.4, 153.4, 161.7. 3-Methyl-4-phenyl-2H-chromen-2-one (2t). Rf = 0.52. White solid (35 mg, 50%). Mp 96−98 °C. 1H NMR (500 MHz, CDCl3): δ 2.00 (s, 3H), 7.01 (dd, J = 8.0 and 1.5 Hz, 1H), 7.12−7.15 (m, 1H), 7.23−7.25 (m, 2H), 7.37 (dd, J = 8.3 and 1.1 Hz, 1H), 7.44−7.51 (m, 2H), 7.52− 7.55 (m, 2H). 13C NMR (125 MHz, CDCl3): δ 14.7, 116.6, 120.7, 122.9, 124.0, 127.0, 128.4, 128.7, 128.9, 130.5, 134.9, 150.6, 152.5,

162.4. HRMS (EI): calcd for C16H12O2 (M+), 236.0837; found, 236.0835. 3,4-Diphenyl-2H-chromen-2-one (2u). Rf = 0.50. Pale yellow solid (48 mg, 54%). Mp 218−220 °C. 1H NMR (500 MHz, CDCl3): δ 7.12−7.14 (m, 4H), 7.17−7.19 (m, 3H), 7.20−7.24 (m, 2H), 7.29− 7.32 (m, 3H), 7.43−7.45 (m, 1H), 7.52−7.55 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 116.8, 120.6, 124.2, 127.0, 127.7, 127.78, 127.83, 128.3, 128.4, 129.4, 130.6, 131.5, 133.9, 134.5, 151.6, 153.3, 161.3. HRMS (EI): calcd for C21H14O2 (M+), 298.0994; found, 298.0992.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b00048. Copies of 1H and 13C NMR spectra of all products, COSY and NOESY NMR spectra of 2b, and ICP-AES data of K2CO3 (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Pham Duy Quang Dao: 0000-0002-2537-1874 Chan Sik Cho: 0000-0001-6416-1741 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This research was supported by the National Strategic ProjectFine Particle of the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT), the Ministry of Environment (ME), and the Ministry of Health and Welfare (MOHW) (2017M3D8A1090658).

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REFERENCES

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