F. Rodríguez-Ramos et al. / Bioorganic Chemistry 50 (2013) 17–25
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d 177.7 (C-4), 156.6 (C-8a), 155.4 (C-2), 133.8 (C-7), 125.9 (C-5),
125.3 (C-4a), 124.9 (C-6), 118.2 (C-8), 113.0 (C-3). EIMS m/z (% rel-
ative intensity): 146 [M+ꢁ] (76), 121 (100), 92 (63).
4.1.2.5. 2-Acetylphenyl isobutyrate 10e. Yellow oil; yield 92%. 1H
NMR (300 MHz, CDCl3): d 7.77 (1H, dd, J = 7.8, 1.5 Hz, H-3), 7.53–
7.48 (1H, m, H-5), 7.30 (1H, ddd, J = 7.7, 7.5, 1.2 Hz, H-4), 7.07
(1H, dd, J = 8.1, 0.9 Hz, H-6), 2.91–2.77 (1H, m, CHCO2), 2.53 (3H,
s, CH3CO), 1.34 (6H, d, J = 7.2 Hz, (CH3)2CH). 13C NMR (75 MHz,
CDCl3): d 197.8 (CO), 175.4 (CO2), 149.2 (C-1), 133.3 (C-5), 131.3
(C-3), 130.1 (C-2), 125.9 (C-4), 123.7 (C-6), 34.3 (CHCO2), 29.5 (CH3-
CO), 18.8 ((CH3)2CH). EIMS m/z (% relative intensity): 206 [M+ꢁ]
(1.3), 121 (100), 71 (78), 43 (34).
4.1.2. Phenolic esters 10a–10h
Phenolic esters were synthetized as described in a previous re-
port [9]. Acyl chloride (8.88 mmol) was added dropwise under N2-
atmosphere to a solution of 2-hydroxyacetophenone (2.69 mmol)
in anhydrous pyridine. Finally, DBU (10.7 mmol) was added drop-
wise to the reaction mixture, which turned into a solid. To this so-
lid 20 mL of anhydrous dichloromethane was added, and the
mixture was heated at a temperature of 30 °C for 6–7 h (monitored
by TLC). The reaction mixture was washed with ice water, acidified
to pH 3–4 using hydrochloric acid at 10%, extracted with ethyl ace-
tate, dried over Na2SO4 and evaporated under reduced pressure.
The crude product was purified by silica-gel flash column chroma-
tography using n-hexane–EtOAc (8:1) as eluent. 1H NMR data for
compounds 10b, 10e and 10f were previously reported [22]. 13C
NMR and EIMS data are included. Compounds 10c, 10d and 10g
are novel.
4.1.2.6. 2-Acetylphenyl 3-methylbutanoate 10f. Yellow oil; yield 95%.
1H NMR (300 MHz, CDCl3): d 7.79 (1H, dd, J = 7.8, 1.8 Hz, H-3),
7.55–7.49 (1H, m, H-5), 7.31 (1H, ddd, J = 7.7, 7.5, 2.1 Hz, H-4),
7.10 (1H, dd, J = 8.1, 1.9 Hz, H-6), 2.55 (3H, s, CH3CO), 2.50 (2H, d,
J = 6.9 Hz, CH2CO2), 2.33–2.19 (1H, m, (CH3)2CH), 1.07 (6H, d,
J = 6.6 Hz, (CH3)2CH). 13C NMR (75 MHz, CDCl3): d 197.6 (CO),
171.4 (CO2), 149.0 (C-1), 133.2 (C-5), 131.1 (C-3), 130.0 (C-2),
125.9 (C-4), 123.7 (C-6), 43.2 (CH2CO2), 29.4 (CH3CO), 25.3 ((CH3)2-
CH), 22.4 ((CH3)2CH). EIMS m/z (% relative intensity): 220 [M+ꢁ]
(1.5), 136 (32), 121 (45), 85 (100).
4.1.2.1. 2-Acetylphenyl acetate 10a. White crystals (n-hexane–ethyl
acetate; 9:1). Mp 71 °C; yield 90%. 1H NMR (300 MHz, CDCl3): d
7.82 (1H, dd, J = 7.8, 1.8 Hz, H-3), 7.54 (1H, m, H-5), 7.33 (1H,
ddd, J = 7.8, 7.7, 1.2 Hz, H-4), 7.12 (1H, dd, J = 8.0, 0.9 Hz, H-6),
2.56 (3H, s, CH3CO), 2.35 (3H, s, CH3CO2). 13C NMR (75 MHz,
CDCl3): d 197.4 (CO), 169.4 (CO2), 148.9 (C-1), 133.3 (C-5), 130.2
(C-3), 125.9 (C-2), 123.7 (C-4), 117.6 (C-6), 29.2 (CH3CO), 22.0 (CH3-
CO2). EIMS m/z (% relative intensity): 178 [M+ꢁ] (1.2), 136 (40), 121
(100), 43 (12).
4.1.2.7. 2-Acetylphenyl 2-ethylbutanoate 10g. Yellow oil; yield 93%.
1H NMR (300 MHz, CDCl3): d 7.74 (1H, dd, J = 7.8, 1.8 Hz, H-3),
7.53–7.47 (1H, m, H-5), 7.29 (1H, ddd, J = 7.6, 7.4, 0.9 Hz, H-4),
7.08 (1H, dd, J = 8.1, 1.2 Hz, H-6), 2.55 (3H, s, CH3CO), 2.51 (1H,
m, (CHCO2), 1.92–1.61 (4H, m, (CH3CH2)2CH), 1.02 (6H, t,
J = 7.5 Hz, (CH3CH2)2CH). 13C NMR (75 MHz, CDCl3): d 198.1 (CO),
174.5 (CO2), 148.9 (C-1), 133.0 (C-5), 131.9 (C-3), 129.8 (C-2),
125.9 (C-4), 123.7 (C-6), 48.6 (CHCO2), 29.7 (CH3CO), 24.5 ((CH3-
CH2)2CH), 11.8 ((CH3CH2)2CH). EIMS m/z (% relative intensity):
234 [M+ꢁ] (2), 136(15), 121 (100), 99 (94), 71(79).
4.1.2.2. 2-Acetylphenyl butyrate 10b. Yellow oil; yield: 93%. 1H NMR
(300 MHz, CDCl3): d 7.78 (1H, dd, J = 7.7, 1.8 Hz, H-3), 7.51 (1H,
ddd, J = 8.1, 7.8, 1.8 Hz, H-5), 7.30 (1H, ddd, J = 7.8, 7.7, 1.2 Hz, H-
4), 7.09 (1H, dd, J = 8.1, 1.2 Hz, H-6), 2.59 (2H, t, J = 7.5 Hz, CH2CO2),
2.53 (3H, s, CH3CO), 1.85–1.73 (2H, m, CH3CH2), 1.04 (3H, t,
J = 7.5 Hz, CH3CH2). 13C NMR (75 MHz, CDCl3): d 197.7 (CO),
172.1 (CO2), 149.1 (C-1), 133.4 (C-5), 131.0 (C-3), 130.2 (C-2),
126.0 (C-4), 123.9 (C-6), 36.2 (CH2CO2), 29.5 (CH3CO), 18.1 (CH3-
CH2), 13.7 (CH3CH2). EIMS m/z (% relative intensity): 206 [M+ꢁ]
(2.8), 136 (98), 121 (65), 71 (100).
4.1.2.8. 2-Acetylphenyl 2-naphthoate 10h. Colorless crystals (n-hex-
ane–ethyl acetate; 8:2). Mp 110 °C; yield 95%. 1H NMR (300 MHz,
CDCl3): d 8.81 (1H, s, NaphH-1), 8.21 (1H, dd, J = 8.5, 1.5 Hz,
NaphH-3), 8.02–7.87 (4H, m, PhH-3, NaphH-4, NaphH-5, NaphH-
8), 7.66–7.55 (3H, m, PhH-5, NaphH-6, NaphH-7), 7.39 (1H, ddd,
J = 7.6, 7.5, 1.2 Hz, PhH-4), 7.29 (1H, dd, J = 8.1, 1.2 Hz, PhH-6),
2.56 (3H, s, CH3CO). 13C NMR (75 MHz, CDCl3): d 197.7 (CO),
165.4 (CO2), 149.5 (C-1), 136.0 (NaphC-4), 133.5 (C-5), 132.6
(NaphC-8a), 132.3 (NaphC-1), 131.4 (NaphC-8), 130.3 (NaphC-3),
129.6 (NaphC-2), 128.8 (NaphC-6), 128.6 (NaphC-4), 127.9
(NaphC-5), 126.9 (C-2), 126.5 (NaphC-7), 126.3 (NaphC-3), 125.5
(C-4), 124.0 (NaphC-6), 29.9 (CH3CO). EIMS m/z (% relative inten-
sity): 290 [M+ꢁ] (5), 155 (100), 127 (55).
4.1.2.3. 2-Acetylphenyl pentanoate 10c. Yellow oil; yield 95%. 1H
NMR (300 MHz, CDCl3): d 7.78 (1H, dd, J = 7.8, 1.8 Hz, H-3), 7.54–
7.48 (1H, m, H-5), 7.30 (1H, ddd, J = 7.6, 7.5, 1.2 Hz, H-4), 7.08
(1H, dd, J = 8.1, 1.2 Hz, H-6), 2.61 (2H, t, J = 7.7 Hz, CH2CO2), 2.53
(3H, s, CH3CO), 1.79–1.69 (2H, m, CH2CH2CO2), 1.50–1.38 (2H, m,
CH3CH2), 0.96 (3H, t, J = 7.4 Hz, CH3CH2). 13C NMR (75 MHz, CDCl3):
d 197.7 (CO), 172.3 (CO2), 149.2 (C-1), 133.4 (C-5), 131.1 (C-3),
130.2 (C-2), 126.0 (C-4), 124.0 (C-6), 34.1 (CH2CO2), 29.5 (CH3CO),
26.7 (CH2CH2CO2), 22.3 (CH3CH2), 13.8 (CH3CH2). EIMS m/z (% rel-
ative intensity): 220 [M+ꢁ] (5), 136 (15), 121 (60), 85 (100).
4.1.3. Chromones 11a–11h
Compounds 11a–11h were prepared in a similar manner as
compounds 10a–10h, starting from the corresponding phenolic es-
ter with 1.0 eq of DBU and pyridine as solvent to reflux at 80 °C for
6 h. The reaction was stopped by adding ice, adjusted to pH 3–4,
extracted with ethyl acetate and purified with a flash chromato-
graphic column eluted with n-hexane–ethyl acetate (8:2). Com-
pounds 11a [23], 11c–11d [24], 11e [25] and 11h [26] have been
previously reported. Compound 11g is new.
4.1.2.4. 2-Acetylphenyl heptanoate 10d. Yellow oil; yield 98%. 1H
NMR (300 MHz, CDCl3): d 7.79 (1H, dd, J = 7.8, 1.5 Hz, H-3), 7.55–
7.49 (1H, m, H-5), 7.31 (1H, ddd, J = 7.8, 7.7, 1.2 Hz, H-4), 7.10
(1H, dd, J = 8.0, 1.2 Hz, H-6), 2.61 (2H, t, J = 7.5 Hz, CH2CO2), 2.54
(3H, s, CH3CO), 1.81–1.68 (2H, m, CH2CH2CO2), 1.39–1.30 (6H, m,
CH3(CH2)3), 0.90 (3H, t, J = 7.1 Hz, CH3CH2). 13C NMR (75 MHz,
CDCl3): d 197.7 (CO), 172.3 (CO2), 149.2 (C-1), 133.4 (C-5), 131.1
(C-3), 130.2 (C-2), 126.0 (C-4), 123.9 (C-6), 34.4 (CH2CO2), 31.5
(CH3CH2CH2), 29.5 (CH3CO), 28.8 (CH2(CH2)2CO2), 24.6 (CH2CH2-
CO2), 22.5 (CH3CH2), 14.1 (CH3CH2). EIMS m/z (% relative intensity):
248 [M+ꢁ] (1.5), 136 (35), 113 (100), 85 (15).
4.1.3.1. 2-Methyl-4H-chromen-4-one 11a. Yellow crystals (n-hex-
ane/ethyl acetate; 8:2). Mp 65 °C; yield 23%. 1H NMR (300 MHz,
CDCl3): d 7.61 (1H, dd, J = 8.1, 1.5 Hz, H-5), 7.56–7.50 (1H, m, H-
7), 7.35–7.26 (2H, m, H-6, H-8), 6.30 (1H, s, H-3), 2.44 (3H, s,
CH3). 13C NMR (75 MHz, CDCl3): d 160.7 (C-4), 153.5 (C-2), 152.2
(C-8a), 131.7 (C-7), 124.5 (C-5), 124.1 (C-4a), 119.9 (C-6), 117.1
(C-8), 115.1 (C-3), 18.6 (CH3). EIMS m/z (% relative intensity): 160
[M+ꢁ] (89), 145 (2), 131 (100).