Download PDF
Synthesis 2011(4): 619-625  
DOI: 10.1055/s-0030-1258402
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

One-Pot Synthesis of Furans Using Base- and Acid-Supported Reagents ‘Na2CO3/Al2O3-PPA/SiO2’

Tadashi Aoyama*a,b, Takashi Nagaokaa, Toshio Takidoa, Mitsuo Kodomaric
a Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University, Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan
Fax: +81(3)32590818; e-Mail: aoyama@chem.cst.nihon-u.ac.jp;
b The Center for Creative Materials Research, Research Institute of Science and Technology, College of Science and Technology, Nihon University, Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan
c Department of Bioscience and Engineering, Shibaura Institute of Technology, Fukasaku, Minuma-ku, Saitama 337-8570, Japan

Further Information

Publication History

Received 1 November 2010
Publication Date:
12 January 2011 (online)

 PDF Download Permissions and Reprints All articles of this category

Abstract

A convenient method for the one-pot synthesis of furans from β-keto esters and α-halo ketones was developed using an acid- and base-supported reagent system ‘Na2CO3/Al2O3-PPA/SiO2’. The condensation reaction of triketones, which are formed from the reaction of β-keto esters with α-halo ketones in the presence of Na2CO3/Al2O3, was promoted by PPA/SiO2 to give the corresponding furans in good yields. This method is simple and easy to perform in comparison with stepwise processes, and the yields are good.

Key words

furan - one-pot synthesis - supported reagents

Furans and their derivatives are important compounds in organic chemistry since these structures can be found in many natural products or therapeutic compounds. [¹-³] Many synthetic methods have been developed for mono-, di-, and trisubstituted furans. [4] The cyclization reaction of 1,4-diketones in the presence of an acid is a classical method for the synthesis of furans. Various acids, such as hydrochloric acid, acetic acid, trifluoroacetic acid, and 4-toluenesulfonic acid, may be used as an acid catalyst for this reaction. [5] [6] Lewis acids, including zinc halides and boron trifluoride-diethyl ether complex, have been also used for the synthesis of furans from 1,4-diketones. [7] 1,4-Diketones are usually prepared by the reaction of 1,3-dicarbonyl compounds with α-halo ketones in the presence of a base catalyst. Thus, the preparation of 1,4-diketones and the cyclization reaction of 1,4-diketones have been carried out in a stepwise process. [8] One-pot synthesis of furans from 1,3-dicarbonyl compounds and α-halo ketones has not been reported because both acid and base catalysts could not co-exist in the same vessel. Recently, Chochois et al. [9] have reported a rapid one-pot furan synthesis via 1,4-carbonylative addition-cyclization reaction. Previously we developed acid and base co-existence reactions using inorganic solid supported acid and base. The process promoted a multistep reaction in one-pot without neutralization of the acid and base. For instance, ‘silica gel supported sodium carbonate and silica gel supported polyphosphoric acid (Na2CO3/SiO2-PPA/SiO2)’ promotes the substitution reaction of α-halo ketones with arenethiols­ to give sulfanyl ketones and the condensation reaction of the sulfanyl ketones to afford arylthio­phenes. [¹0] [¹¹] The process also promotes the following reactions: Michael addition of arenethiols to α,β-unsaturated aldehyde by Na2CO3/SiO2, and cyclization of the product by PPA/SiO2 to form thiochromanes in one pot. [¹²] We attempted to expand the scope of this process to the one-pot synthesis of furans. In this paper, we describe the one-pot synthesis of furans from β-keto esters and α-halo ketones using Na2CO3/Al2O3-PPA/SiO2. The reaction of ethyl ace­toacetate (1a) and phenacyl bromide (2a) was employed as a model reaction for the determination of the optimum reaction conditions. The reaction of 1a with 2a in the presence of various inorganic solid supported bases afforded 1,4-dicarbonyl compound 3a (Scheme  [¹] ). Silica gel supported sodium carbonate (Na2CO3/SiO2) gave 3a in 60% yield, whereas alumina-supported sodium carbonate (Na2CO3/Al2O3) afforded 3a in 86% yield. Using alumina-supported potassium fluoride (KF/Al2O3) as the base catalyst gave 3a in 84% yield. In this case, a large quantity of KF/Al2O3 was required to obtain 3a in high yield. PPA/SiO2 catalyzed cyclocondensation of 3a to give 4a. In the case of the cyclocondensation of sulfanyl ketones to give arylthiophenes, the catalytic activity of PPA/SiO2 depended on the loading ratio of PPA. [¹¹] In contrast, cyclocondensation of 3a was not affected by the loading ratio of PPA onto SiO2. For instance, 4a was obtained in 91% yield from the reaction using either PPA/SiO2 (30 wt%) or PPA/SiO2 (10 wt%).

Scheme 1

Table 1 One-Pot Synthesis of 4a Using a Combination of Base and Acid

Entry Reagent system
 Yielda (%)
Base Acid 3a 4a
1 Na2CO3 PPA no reaction
2 Na2CO3/Al2O3 b none 86  0
3 none PPA/SiO2 c no reaction
4 Na2CO3/Al2O3 b PPA/SiO2 c 0 73
a Isolated yield.
b Na2CO3/Al2O3 (1.5 mmol/g, 1.5g).
c PPA/SiO2 (30 wt%, 1.0g).

We attempted to synthesize 4a in one-pot using Na2CO3/Al2O3 (1.5 mmol/g) and PPA/SiO2 (30 wt%). As shown in Table  [¹] , when the reaction of 1a with 2a was carried out in the presence of Na2CO3/Al2O3 and PPA/SiO2 (30 wt%), the isolated yield of 4a was 73% (Table  [¹] , entry 4). The yield of 4a obtained by this method was as good as the stepwise process. Moreover the total reaction time was reduced and the handling was simple and easer compared to the stepwise process. The reaction did not occur when granular Na2CO3 and viscous PPA in toluene were used (Table  [¹] , entry 1). When the reaction was carried out in the presence of Na2CO3/Al2O3 only 3a was obtained and the cyclocondensation of 3a did not occur (Table  [¹] , entry 2). On the other hand, when the reaction was carried out in the presence of PPA/SiO2, starting materials 1a and 2a were recovered quantitatively.

Some dicarbonyl compounds and α-halo ketones were used in this one-pot reaction and the results are summarized in Table  [²] . In the reactions of 1a with phenacyl halides, 4a was obtained in good yield when phenacyl bromide was used (Table  [²] , entry 1). In contrast, when phenacyl chloride was used instead of phenacyl bromide, the substitution reaction did not proceed effectively and 4a was obtained in moderate yield (Table  [²] , entry 2). Though this reaction was carried out under more severe conditions, at 110 ˚C for 24 hours, the yield did not increase satisfactorily. Using phenacyl iodide, deiodination occurred and acetophenone was formed along with 4a (Table  [²] , entry 3). Yields of the corresponding furans decreased according to the increasing size of substituent R¹ in compound 1 (Table  [²] , entries 1 and 4-7). On the other hand, the yields were not affected by the substituent R² except in the case of the tert-butyl group. Any acetoacetic acid esters except tert-butyl ester gave furans in moderate yield. The tert-butyl ester afforded the corresponding furans in low yields because the tert-butyl group is sensitive to acid and is easily hydrolyzed. This one-pot reaction using the tert-butyl ester was carried out separately. Reaction of tert-butyl acetoacetates with phenacyl bromide in the presence of KF/Al2O3 was carried out, and then the reaction mixture was filtered to remove KF/Al2O3. PPA/SiO2 was added to the filtrate and the mixture was stirred at 80 ˚C for one hour; 3-acetyl-2-hydroxy-5-phenylfuran was obtained in 59% yield. A method for the synthesis of this compound has been reported by Stauffer et al. [6] They have synthesized this compound using sodium hydride and trifluoroacetic acid in two steps. Various α-halo ketones were also able converted into furans in moderate to good yields, but chloroacetone did not give the corresponding furan (Table  [²] , entries 12-20). sec-α-Halo ketones gave the products in poor yields. In this reaction, the first step, C-alkylation, did not proceed successfully.

Table 2 One-Pot Synthesis of Furans Using Various β-Keto Esters and α-Halo Ketones (continued)

Entry R¹ R² R³ R4 X Product Yielda (%)
 1 Me Et Ph H Br 4a 73
 2 Me Et Ph H Cl 4a 34 (47)b
 3 Me Et Ph H I 4a 38
 4 Pr Et Ph H Br 4b 35 (47)c
 5 (CH2)6Me Et Ph H Br 4c 27
 6 Bn Et Ph H Br 4d 17
 7 Ph Et Ph H Br 4e  8 (43)d
 8 Me Bn Ph H Br 4f 70
 9 Me allyl Ph H Br 4g 76
10 Me (CH2)2OMe Ph H Br 4h 62
11 Me t-Bu Ph H Br 4i  3
12 Me Et 4-ClC6H4 H Br 4j 56
13 Me Et 4-MeOC6H4 H Br 4k 77
14 Me Et 4-MeC6H4 H Br 4l 75
15 Me Et 3-MeC6H4 H Br 4m 59
16 Me Et 2-MeC6H4 H Br 4n 38
17 Me Et 1-naphthyl H Br 4o 38
18 Me Et 2-naphthyl H Br 4p 73
19 Me Et t-Bu H Br 4q 21
20 Me Et Me H Cl 4r  0
21 Me Et Ph Me Br 4s 14
22 Me Et Ph Ph Br 4t  0
a Isolated yield.
b 110 ˚C, 24 h.
c 110 ˚C, 1 h.
d 110 ˚C, 2 h.

When various β-diketones were used instead of β-keto esters for this reaction, the corresponding furans were obtained in good yields (Table  [³] ). The reaction of 1,3-diphenylpropane-1,3-dione required high temperatures and a long reaction time to obtain the product 6c in 47% yield (Table  [³] , entry 3). The reaction of cyclohexane-1,3-diones were carried out at 110 ˚C to afford the corresponding dihydrobenzofuran-4-ones 6d and 6e in moderate yields along with the regioisomers 6d′ and 6e′, respectively (Table  [³] , entries 4 and 5). Asymmetric β-diketone, 1-phenylbutane-1,3-dione, gave 3-benzoyl-2-methyl-5-phenylfuran (6f) and 3-acetyl-2,5-diphenylfuran (6f′) in 57% and 20% yields, respectively (Table  [³] , entry 6). When this reaction was carried out using PPA/Bentonite instead of PPA/SiO2, the yield of 6f increased to 67% and the yield of 6f′ decreased to 12%. Cyclocondensation reaction of 7 was carried out using viscous polyphosphoric acid (PPA) and various inorganic-supported acids. PPA/Bentonite was the most effective among the inorganic supported-acids tested and gave compound 6f selectively (Table  [4] ).

In conclusion we have developed a simple and efficient method for the one-pot synthesis of furans from 1,3-diketones and α-halo ketones using Na2CO3/Al2O3-PPA/SiO2. This procedure has easy handling compared to the stepwise process and the yields are at least as good as those of the stepwise procedure. The reaction time was shorter than for the stepwise process. Many combinations of 1,3-diketones and α-halo ketones produced the corresponding furans in moderate to good yields. The use of PPA/Bentonite instead of PPA/SiO2 increased the yield of 6f, and an examination of these selective reactions is now under investigation.

Table 3 Reaction of 2a and Various Diketones

Entry R¹ R² Temp (˚C) Time (h) Product Yielda (%)
1 Me Me  80  2 6a 79
2 Et Et  80  2 6b 58
3 Ph Ph 110 24 6c 47
4 CH2CMe2CH2
110 24 6d 51 (18)b
5 CH2CH2CH2
110  3 6e 38 (10)c
6 Me Ph  80  2 6f 57 (20)d
7e Me Ph  80  2 6f 67 (12)d
a Isolated yield.
b Yield of 6,6-dimethyl-3-phenyl-6,7-dihydrobenzofuran-4(5H)-one (6d′).
c Yield of 3-phenyl-6,7-dihydrobenzofuran-4(5H)-one (6e′).
d Yield of 3-acetyl-2,5-diphenylfuran (6f′).
e PPA/Bentonite was used instead of PPA/SiO2.
Table 4 Reaction of 7 and Various Acids

Entry Acid Yielda (%)
6f 6f′
1 PPA/SiO2 (30 wt%, 0.5 g) 69 31
2 PPA/Bentonite (10 wt%, 1.0 g) 83 16
3 NaHSO4/SiO2 (2.1 mmol/g, 0.5 g) 60 36
4 ZnCl2/SiO2 (1.5 mmol/g, 1.0 g) 63 30
5b PPA (7.0 g) 63 24
a Isolated yield.
b Neat.

Melting points were determined on a Yanako Micro melting point apparatus. Elemental analyses were performed on a Yanako CHNcorder MT-5. NMR spectra were recorded on a JEOL JNM-GX400 spectrometer or a JEOL JNM-ECX400. Tetramethylsilane (δ = 0 ppm) was used as an internal standard for ¹H NMR and CDCl3 (δ = 77.0 ppm) for ¹³C NMR. Mass analyses were performed on an Agilent G1969 LC/MDS TOF spectrometer. IR spectra were recorded on a Thermo Electron Nicolet 380 spectrometer.

Alumina-Supported Sodium Carbonate

Alumina (ICN Biomedical N-Super 1, 8.41 g) was added to a soln of Na2CO3 (10 mmol, 1.59 g) in distilled H2O, and the mixture was stirred at r.t. for 0.5 h. The water was removed by rotary evaporator under reduced pressure below 60 ˚C, and the resulting reagent was dried in vacuo (13.3 mbar) at r.t. for 5 h.

Silica Gel Supported PPA

PPA (6.0 g) and CHCl3 (150 mL) were placed in the round-bottom flask, and the mixture was stirred at 50 ˚C for 1 h. Silica gel [Wakogel­ C-200 (Wako Pure Chemical Ind. Ltd), 14.0 g], which was dried in vacuo at 160 ˚C for 2 h, was added to the mixture, and the mixture was stirred for another 1 h. The CHCl3 was removed with rotary evaporator and the resulting solid was dried in vacuo at r.t. for 3 h.

Furans 4 and 6; General Procedure

A mixture of β-dicarbonyl (3 mmol), α-halo ketone (2 mmol), PPA/SiO2 (30 wt%, 1.0 g), and Na2CO3/Al2O3 (1.5 mmol, 1.5 g) was stirred in toluene (10 mL) at 80 ˚C for 2 h, and then the used supported reagents were removed by filtration. The filtrate was evaporated to leave crude product, which was purified by column chromatography.

Ethyl 2-Methyl-5-phenylfuran-3-carboxylate (4a) [¹³]

Yellow oil.

IR (neat): 1717, 1234, 1098, 760 cm-¹.

¹H NMR (CDCl3): δ = 1.37 (t, J = 7.1 Hz, 3 H), 2.65 (s, 3 H), 4.31 (q, J = 7.1 Hz, 2 H), 6.88 (s, 1 H), 7.24-7.28 (m, 1 H), 7.36-7.40 (m, 2 H), 7.62-7.65 (m, 2 H).

¹³C NMR (CDCl3): δ = 13.9, 14.4, 60.2, 105.5, 115.4, 123.6, 127.6, 128.7, 130.1, 151.7, 158.6, 164.0.

HRMS (TOF-CI): m/z [M + H]+ calcd for C14H15O3: 231.1021; found: 231.1030.

Anal. Calcd for C14H14O3: C, 73.03; H, 6.13. Found: C, 73.03; H, 6.12.

Ethyl 5-Phenyl-2-propylfuran-3-carboxylate (4b)

Yellow oil.

IR (neat): 2963, 2933, 1717, 1230, 1107, 1054, 760 cm-¹.

¹H NMR (CDCl3): δ = 1.00 (t, J = 7.3 Hz, 3 H), 1.37 (t, J = 7.3 Hz, 3 H), 1.73-1.82 (m, 2 H), 3.03 (t, J = 7.3 Hz, 2 H), 4.31 (q, J = 7.3 Hz, 2 H), 6.88 (s, 1 H), 7.25-7.28 (m, 1 H), 7.36-7.40 (m, 2 H), 7.63-7.66 (m, 2 H).

¹³C NMR (CDCl3): δ = 13.8, 14.3, 21.6, 29.7, 60.1, 105.5, 115.1, 123.6, 127.6, 128.7, 130.2, 151.6, 162.5, 164.0.

HRMS (TOF-CI): m/z [M + H]+ calcd for C16H19O3: 259.1334; found: 259.1337.

Anal. Calcd for C16H18O3: C, 74.39; H, 7.02. Found: C, 74.39; H, 7.08.

Ethyl 2-Heptyl-5-phenylfuran-3-carboxylate (4c)

Yellow oil.

IR (neat): 2928, 2856, 1717, 1229, 1065, 760 cm-¹.

¹H NMR (CDCl3): δ = 0.88 (t, J = 7.3 Hz, 3 H), 1.19-1.42 (m, 8 H), 1.37 (t, J = 7.0 Hz, 3 H), 1.74 (quint, J = 7.3 Hz, 2 H), 3.04 (t, J = 7.3 Hz, 2 H), 4.31 (q, J = 7.3 Hz, 2 H), 6.88 (s, 1 H), 7.24-7.28 (m, 1 H), 7.35-7.39 (m, 2 H), 7.62-7.65 (m, 2 H).

¹³C NMR (CDCl3): δ = 14.0, 14.3, 22.6, 27.7, 28.1, 29.0, 29.2, 31.7, 60.1, 105.4, 114.9, 123.6, 127.5, 128.6, 130.2, 151.5, 162.7, 164.0.

HRMS (TOF-CI): m/z [M + H]+ calcd for C20H27O3: 315.1960; found: 315.1960.

Ethyl 2-Benzyl-5-phenylfuran-3-carboxylate (4d)

White solid; mp 66 ˚C.

IR (neat): 2980, 2923, 1708, 1259, 1230, 1083, 760 cm-¹.

¹H NMR (CDCl3): δ = 1.37 (t, J = 7.1 Hz, 3 H), 4.33 (q, J = 7.1 Hz, 2 H), 4.41 (s, 2 H), 6.91 (s, 1 H), 7.20-7.38 (m, 8 H), 7.61-7.63 (m, 2 H).

¹³C NMR (CDCl3): δ = 14.4, 33.7, 60.4, 105.5, 115.6, 123.8, 126.6, 127.8, 128.5, 128.7, 128.7, 129.9, 137.5, 152.3, 159.6, 163.8.

HRMS (TOF-CI): m/z [M + H]+ calcd for C20H19O3: 307.1334; found: 307.1326.

Anal. Calcd for C20H18O3: C, 78.41; H, 5.92. Found: C, 78.38; H, 6.25.

Ethyl 2,5-Diphenylfuran-3-carboxylate (4e) [¹4]

White solid; mp 71 ˚C.

IR (neat): 3130, 2983, 2909, 1703, 1484, 1266, 1230, 1096, 761, 690 cm-¹.

¹H NMR (CDCl3): δ = 1.37 (t, J = 7.1 Hz, 3 H), 4.34 (q, J = 7.2 Hz, 2 H), 7.01 (s, 1 H), 7.30-7.74 (m, 1 H), 7.38-7.48 (m, 5 H), 7.74 (d, J = 7.6 Hz, 2 H), 8.08 (d, J = 7.6 Hz, 2 H).

¹³C NMR (CDCl3): δ = 14.3, 60.6, 107.9, 115.8, 123.6, 124.0, 128.1, 128.1, 128.4, 128.8, 129.3, 129.8, 152.3, 156.5, 163.5.

HRMS (TOF-CI): m/z [M + H]+ calcd for C19H17O3: 293.1178; found: 293.1179.

Anal. Calcd for C19H16O3: C, 78.06; H, 5.52. Found: C, 78.07; H, 5.49.

Benzyl 2-Methyl-5-phenylfuran-3-carboxylate (4f)

Yellow oil.

IR (neat): 1708, 1224, 1086, 757 cm-¹.

¹H NMR (CDCl3): δ = 2.65 (s, 3 H,), 5.30 (s, 2 H), 6.67 (s, 1 H), 7.25-7.28 (m, 1 H), 7.30-7.44 (m, 7 H), 7.63 (d, J = 7.2 Hz, 2 H).

¹³C NMR (CDCl3): δ = 14.0, 66.0, 105.4, 115.1, 123.7, 127.7, 128.1, 128.2, 128.6, 128.7, 130.0, 136.2, 151.8, 159.0, 163.8.

HRMS (TOF-CI): m/z [M + H]+ calcd for C19H17O3: 293.1178; found: 293.1185.

Allyl 2-Methyl-5-phenylfuran-3-carboxylate (4g)

Yellow oil.

IR (neat): 1717, 1231, 1092, 760 cm-¹.

¹H NMR (CDCl3): δ = 2.65 (s, 3 H), 4.76 (dt, J = 5.50, 1.4 Hz, 2 H), 5.28 (m, 1 H), 5.40 (m, 1 H), 5.97-6.07 (m, 1 H), 6.90 (s, 1 H), 7.24-7.28 (m, 1 H), 7.36-7.39 (m, 2 H), 7.62-7.65 (m, 2 H).

¹³C NMR (CDCl3): δ = 13.9, 64.8, 105.4, 115.0, 118.1, 123.6, 127.6, 128.7, 129.9, 132.3, 151.7, 158.9, 163.6.

HRMS (TOF-CI): m/z [M + H]+ calcd for C15H15O3: 243.1015; found: 243.1024.

2-Methoxyethyl 2-Methyl-5-phenylfuran-3-carboxylate (4h)

Yellow oil.

IR (neat): 2888, 1717, 1233, 1096 cm-¹.

¹H NMR (CDCl3): δ = 2.66 (s, 3 H), 3.43 (s, 3 H), 3.69-3.71 (m, 2 H), 4.40-4.42 (m, 2 H), 6.91 (s, 1 H), 7.26-7.28 (m, 1 H), 7.38 (t, J = 7.4 Hz, 2 H), 7.64 (d, J = 7.4 Hz, 2 H).

¹³C NMR (CDCl3): δ = 13.9, 59.0, 63.2, 70.6, 102.5, 105.5, 115.2, 123.6, 127.6, 128.7, 130.0, 151.7, 159.0, 164.0.

HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O4: 261.1127; found: 261.1128.

tert -Butyl 2-Methyl-5-phenylfuran-3-carboxylate (4i)

Yellow oil.

¹H NMR (CDCl3): δ = 1.58 (s, 9 H), 2.62 (s, 3 H), 6.83 (s, 1 H), 7.26 (t, J = 7.3 Hz, 1 H), 7.37 (t, J = 7.8 Hz, 2 H), 7.63 (d, J = 7.3 Hz, 2 H).

¹³C NMR (CDCl3): δ = 14.2, 28.6, 106.1, 117.1, 123.9, 127.8, 129.0, 130.5, 151.7, 158.3, 163.8.

Ethyl 5-(4-Chlorophenyl)-2-methylfuran-3-carboxylate (4j)

Yellow solid; mp 79 ˚C.

IR (neat): 1700, 1248, 1090, 832 cm-¹.

¹H NMR (CDCl3): δ = 1.37 (t, J = 7.1 Hz, 3 H), 2.64 (s, 3 H), 4.31 (q, J = 7.1 Hz, 2 H), 6.88 (s, 1 H), 7.35 (d, J = 8.3 Hz, 2 H), 7.56 (d, J = 8.3 Hz, 2 H).

¹³C NMR (CDCl3): δ = 13.9, 14.4, 60.27, 106.0, 115.5, 124.8, 128.6, 128.9, 133.3, 150.6, 158.9, 163.9.

HRMS (TOF-CI): m/z [M + H]+ calcd for C14H14ClO3: 265.0631; found: 265.0634.

Anal. Calcd for C14H13ClO3: C, 63.52; H, 4.95. Found: C, 63.43; H, 4.97.

Ethyl 5-(4-Methoxyphenyl)-2-methylfuran-3-carboxylate (4k) [¹5]

Yellow solid; mp 58 ˚C.

IR (neat): 1697, 1502, 1246, 1026, 831 cm-¹.

¹H NMR (CDCl3): δ = 1.37 (t, J = 7.1 Hz, 3 H), 2.63 (s, 3 H), 3.83 (s, 3 H), 4.31 (q, J = 7.1 Hz, 2 H), 6.74 (s, 1 H), 6.92 (d, J = 8.8 Hz, 2 H), 7.57 (d, J = 8.8 Hz, 2 H).

¹³C NMR (CDCl3): δ = 13.9, 14.4, 55.3, 60.1, 103.8, 114.2, 115.3, 123.1, 125.1, 151.7, 152.3, 159.2, 164.2.

HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O4: 261.1127; found: 261.1125.

Anal. Calcd for C15H16O4: C, 69.22; H, 6.20. Found: C, 69.14; H, 6.21.

Ethyl 2-Methyl-5-(4-tolyl)furan-3-carboxylate (4l)

Yellow solid; mp 82 ˚C.

IR (neat): 1698, 1427, 1229, 1098, 819, 779 cm-¹.

¹H NMR (CDCl3): δ = 1.37 (t, J = 7.1 Hz, 3 H), 2.36 (s, 3 H), 2.64 (s, 3 H), 4.31 (q, J = 7.1 Hz, 2 H), 6.82 (s, 1 H), 7.15-7.20 (m, 2 H), 7.53 (d, J = 8.3 Hz, 2 H).

¹³C NMR (CDCl3): δ = 13.9, 14.4, 21.6, 60.2, 104.7, 115.3, 123.6, 127.4, 129.4, 137.5, 151.9, 158.2, 164.1.

HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O3: 245.1178; found: 245.1172.

Anal. Calcd for C15H16O3: C, 73.75; H, 6.60. Found: C, 73.70; H, 6.61.

Ethyl 2-Methyl-5-(3-tolyl)furan-3-carboxylate (4m)

Yellow oil.

IR (neat): 1711, 1229, 1096, 772 cm-¹.

¹H NMR (CDCl3): δ = 1.39 (t, J = 7.1 Hz, 3 H), 2.38 (s, 3 H), 2.65 (s, 3 H), 4.32 (q, J = 7.1 Hz, 2 H), 6.86 (s, 1 H), 7.08 (d, J = 7.6 Hz, 1 H), 7.27 (t, J = 7.6 Hz, 1 H), 7.40-7.52 (m, 2 H).

¹³C NMR (CDCl3): δ = 13.9, 14.4, 21.5, 60.2, 105.3, 115.3, 120.8, 124.3, 128.4, 128.6, 130.0, 138.3, 151.8, 158.5, 164.1.

HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O3: 245.1178; found: 245.1173.

Ethyl 2-Methyl-5-(2-tolyl)furan-3-carboxylate (4n)

Yellow oil.

IR (neat): 1706, 1225, 1087, 758 cm-¹.

¹H NMR (CDCl3): δ = 1.38 (t, J = 7.1 Hz, 3 H), 2.49 (s, 3 H), 2.65 (s, 3 H), 4.32 (q, J = 7.1 Hz, 2 H), 6.77 (s, 1 H), 7.19-7.30 (m, 3 H), 7.68 (d, J = 6.8Hz, 1 H).

¹³C NMR (CDCl3): δ = 13.9, 14.4, 21.9, 60.2, 89.2, 109.1, 126.0, 126.7, 127.7, 129.3, 131.1, 134.6, 144.3, 151.1, 158.2.

HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O3: 245.1178; found: 245.1175.

Ethyl 2-Methyl-5-naphthalen-1-ylfuran-3-carboxylate (4o)

Yellow oil.

IR (neat): 3050, 2980, 2928, 1716, 1239, 1085, 776 cm-¹.

¹H NMR (CDCl3): δ = 1.39 (t, J = 7.1 Hz, 3 H), 2.71 (s, 3 H), 4.35 (q, J = 7.1 Hz, 2 H), 6.98 (s, 1 H), 7.48-7.55 (m, 3 H), 7.71-7.73 (m, 1 H), 7.83-7.89 (m, 2 H), 8.35-8.37 (m, 1 H).

¹³C NMR (CDCl3): δ = 14.0, 14.4, 60.2, 109.8, 115.2, 125.2, 125.2, 126.0, 126.1, 126.7, 127.7, 128.6, 128.8, 130.2, 133.9, 151.0, 158.9, 164.1.

HRMS (TOF-CI): m/z [M + H]+ calcd for C18H17O3: 281.1178; found: 281.1182

Ethyl 2-Methyl-5-naphthalen-2-ylfuran-3-carboxylate (4p)

White solid; mp 96 ˚C.

IR (neat): 3114, 2978, 1705, 1439, 1238, 1103 cm-¹.

¹H NMR (CDCl3): δ = 1.39 (t, J = 7.2 Hz, 3 H), 2.70 (s, 3 H), 4.33 (q, J = 7.2 Hz, 2 H), 7.00 (s, 1 H), 7.44-7.51 (m, 2 H), 7.72 (d, J = 8.5 Hz, 1 H), 7.80-7.87 (m, 3 H), 8.12 (s, 1 H).

¹³C NMR (400 MHz, CDCl3): δ = 14.0, 14.4, 60.3, 106.1, 115.6, 122.0, 122.0, 126.0, 126.6, 127.3, 127.8, 128.1, 128.5, 132.7, 133.4, 151.7, 158.9, 164.1.

HRMS (TOF-CI): m/z [M + H]+ calcd for C18H17O3: 281.1178; found: 281.1176.

Ethyl 5- tert -Butyl-2-methylfuran-3-carboxylate (4q)

Yellow oil.

IR (neat): 2970, 1777, 1717, 1254 cm-¹.

¹H NMR (CDCl3): δ = 1.25 (s, 9 H), 1.34 (t, J = 7.2 Hz, 3 H), 2.54 (s, 3 H), 4.27 (q, J = 7.2 Hz, 2 H), 6.19 (s, 1 H).

¹³C NMR (CDCl3): δ = 4.1, 14.8, 29.2, 32.7, 60.2, 103.0, 113.8, 157.8, 162.5, 164.9.

HRMS (TOF-CI): m/z [M + H]+ calcd for C12H19O3: 211.1334; found: 211.1328.

Ethyl 2,4-Dimethyl-5-phenylfuran-3-carboxylate (4s) [¹6]

Yellow oil.

IR (neat): 1715, 1237, 1098 cm-¹.

¹H NMR (CDCl3): δ = 1.38 (t, J = 7.1 Hz, 3 H), 2.46 (s, 3 H), 2.61 (s, 3 H), 4.32 (q, J = 7.1 Hz, 2 H), 7.27-7.31 (m, 1 H), 7.39-7.43 (m, 2 H), 7.56-7.79 (m, 2 H).

¹³C NMR (CDCl3): δ = 10.9, 14.4, 14.5, 59.9, 115.3, 116.9, 126.1, 127.2, 128.5, 131.0, 147.7, 158.4, 164.8.

HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O3: 245.1178; found: 245.1176.

3-Acetyl-2-methyl-5-phenylfuran (6a) [¹5]

White solid; mp 53 ˚C.

IR (neat): 3108, 3064, 1672, 1609, 1236, 759, 690 cm-¹.

¹H NMR (CDCl3): δ = 2.45 (s, 3 H), 2.66 (s, 3 H), 6.84 (s, 1 H), 7.26-7.30 (m, 1 H), 7.37-7.41 (m, 2 H), 7.64 (d, J = 8.4 Hz, 2 H).

¹³C NMR (CDCl3): δ = 14.5, 29.1, 105.0, 123.2, 123.6, 128.7, 129.9, 151.2, 157.9, 194.1.

HRMS (TOF-CI): m/z [M + H]+ calcd for C13H13O2: 201.0916; found: 201.0914.

Anal. Calcd for C13H12O2: C, 77.98; H, 6.04. Found: C, 78.24; H, 6.05.

1-(2-Ethyl-5-phenylfuran-3-yl)propan-1-one (6b)

White solid; mp 36 ˚C.

IR (neat): 2974, 2933, 1676, 1552, 1200, 920, 758 cm-¹.

¹H NMR (CDCl3): δ = 1.19 (t, J = 7.3 Hz, 3 H), 1.32 (t, J = 7.3 Hz, 3 H), 2.80 (q, J = 7.3 Hz, 2 H), 3.09 (q, J = 7.3 Hz, 2 H), 6.85 (s, 1 H), 7.26-7.30 (m, 1 H), 7.37-7.41 (m, 2 H), 7.64-7.66 (m, 2 H).

¹³C NMR (CDCl3): δ = 7.8, 12.0, 21.8, 34.4, 104.6, 121.7, 123.6, 127.7, 128.7, 130.0, 151.5, 162.7, 197.0.

HRMS (TOF-CI): m/z [M + H]+ calcd for C15H17O2: 229.1229; found: 229.1230.

Anal. Calcd for C15H16O2: C, 78.92; H, 7.06. Found: C, 79.07; H, 7.11.

2-Benzoyl-2,5-diphenylfuran (6c)

Yellow oil.

IR (neat): 3059, 1682, 1656, 1448, 1279, 769, 690 cm-¹.

¹H NMR (CDCl3): δ = 6.90 (s, 1 H), 7.31-7.51 (m, 9 H), 7.72-7.89 (m, 6 H).

¹³C NMR (CDCl3): δ = 108.6, 122.7, 124.0, 127.3, 128.1, 128.3, 128.3, 128.6, 128.8, 128.9, 129.6, 129.7, 132.8, 137.9, 152.3, 154.9, 191.6.

HRMS (TOF-CI): m/z [M + H]+ calcd for C23H17O2: 325.1229; found: 325.1233.

6,6-Dimethyl-2-phenyl-6,7-dihydrobenzofuran-4(5 H )-one (6d)

Yellow solid; mp 90 ˚C.

IR (neat): 3100, 2958, 1674, 1437, 1225, 764, 691 cm-¹.

¹H NMR (CDCl3): δ = 1.18 (s, 6 H), 2.41 (s, 2 H), 2.83 (s, 2 H), 6.89 (s, 1 H), 7.26-7.32 (m, 1 H), 7.38-7.44 (m, 2 H), 7.66 (d, J = 7.3 Hz, 2 H).

¹³C NMR (CDCl3): δ = 28.6, 35.3, 37.5, 52.0, 100.7, 121.7, 123.9, 128.0, 128.8, 129.8, 154.5, 165.8, 193.9.

HRMS (TOF-CI): m/z [M + H]+ calcd for C16H17O2: 241.1229; found: 241.1230.

Anal. Calcd for C16H16O2: C, 79.97; H, 6.71. Found: C, 80.05; H, 6.70.

6,6-Dimethyl-3-phenyl-6,7-dihydrobenzofuran-4(5 H )-one (6d′)

Yellow solid; mp 103 ˚C.

IR (neat): 3122, 2948, 2923, 1669, 1471, 756, 690 cm-¹.

¹H NMR (CDCl3): δ = 1.15 (s, 6 H), 2.42 (s, 2 H), 2.80 (s, 2 H), 7.28-7.32 (m, 1 H), 7.35-7.38 (m, 2 H), 7.44 (s, 1 H), 7.64 (d, J = 8.0 Hz, 2 H).

¹³C NMR (CDCl3): δ = 28.5, 35.0, 37.9, 53.3, 117.7, 125.5, 127.7, 128.3, 128.6, 130.7, 139.7, 167.7, 193.8.

HRMS (TOF-CI): m/z [M + H]+ calcd for C16H17O2: 241.1229; found: 241.1232.

2-Phenyl-6,7-dihydrobenzofuran-4(5 H )-one (6e) [¹³]

Yellow solid; mp 136 ˚C.

IR (neat): 3100, 3053, 2945, 1667, 1436, 764 cm-¹.

¹H NMR (CDCl3): δ = 2.21 (m, J = 6.4 Hz, 2 H), 2.53 (t, J = 6.4 Hz, 2 H), 2.95 (t, J = 6.4 Hz, 2 H), 6.89 (s, 1 H), 7.28-7.31 (m, 1 H), 7.37-7.41 (m, 2 H), 7.64-7.66 (m, 2 H).

¹³C NMR (CDCl3): δ = 22.5, 23.4, 37.6, 100.8, 122.9, 123.9, 128.0, 128.7, 129.7, 154.2, 166.7, 194.5.

HRMS (TOF-CI): m/z [M + H]+ calcd for C14H13O2: 213.0916; found: 213.0918.

3-Benzoyl-2-methyl-5-phenylfuran (6f) [¹7]

Yellow oil.

IR (neat): 3059, 2919, 1652, 1262, 901, 762 cm-¹.

¹H NMR (CDCl3): δ = 2.60 (s, 3 H), 6.81 (s, 1 H), 7.27 (t, J = 7.3 Hz, 1 H), 7.36-7.40 (m, 2 H), 7.47-7.50 (m, 2 H), 7.56-7.59 (m, 1 H), 7.64-7.67 (m, 2 H), 7.83-7.85 (m, 2 H).

¹³C NMR (CDCl3): δ = 14.3, 106.5, 122.3, 123.7, 127.7, 128.4, 128.7, 128.9, 129.9, 132.2, 139.0, 151.5, 158.9, 191.2.

HRMS (TOF-CI): m/z [M + H]+ calcd for C18H15O2: 263.1072; found: 263.1075.

Anal. Calcd for C18H14O2: C, 82.42; H, 5.38. Found: C, 82.28; H, 5.40.

3-Acetyl-2,5-diphenylfuran (6f′)

Yellow solid; mp 58 ˚C.

IR (neat): 3059, 1683, 1483, 1229, 770, 702 cm-¹.

¹H NMR (CDCl3): δ = 2.41 (s, 3 H), 6.97 (s, 1 H), 7.28 (t, J = 7.3 Hz, 1 H), 7.36-7.46 (m, 5 H), 7.69 (d, J = 7.3 Hz, 2 H), 7.95-7.97 (m, 2 H).

¹³C NMR (CDCl3): δ = 29.7, 107.0, 123.8, 124.0, 128.0, 128.2, 128.4, 128.7, 129.5, 129.6, 129.8, 152.4, 155.5, 193.8.

HRMS (TOF-CI): m/z [M + H]+ calcd for C18H15O2: 263.1072; found: 263.1076.

Anal. Calcd for C18H14O2: C, 82.42; H, 5.38. Found: C, 82.74; H, 5.24.

   Permissions and Reprints All articles of this category

Scheme 1