SYNTHESIS
December 1998
1797
9-(Methoxycarbonyl)nonanoic acid (9e): oily white solid; yield:
1.22 g (58%); bp 168–170°C/3 Torr; mp 41°C (lit.20 mp 40–41°C).
1H NMR: δ = 1.32 (br s, 8H, 4 × CH2), 1.59–1.63 (m, 4H, 2 × CH2),
2.27–2.33 (m, 4H, 2 × CH2), 3.66 (s, 3H, OCH3).
Synthesis of 8a–f; General Procedure:
To a stirred solution of deoxybenzoin 7 (1.20 g, 4.0 mmol) in anhyd
pyridine (10 mL) under argon at 0°C was added the acid chloride 4
(4.80 mmol) dropwise. The mixture was stirred for 2 d at r.t., the
pyridine was removed in vacuo and the resultant residue dissolved in
CHCl3 (20 mL), washed with water (2 × 10 mL), and dried (anhyd
MgSO4). Filtration and concentration provided an oil which was pu-
rified by flash chromatography (Et2O/hexane 3:2) to afford the pure
substituted deoxybenzoin. (For 13C NMR data of substituted deoxy-
benzoins and isoflavones see Tables 1 and 2).
13C NMR: δ = 20.37, 26.1, 26.18, 30.3, 30.35, 31.88, 35.28, 36.34
(CH2), 175.73 (CO2Me), 177.9 (CO2H).
Formation of 4a–f; General Procedure:
To the monoester 9 (20 mmol) was added oxalyl chloride (30 mmol)
under argon at r.t. Once evolution of gas had ceased (ca. 30 min), the
mixture was heated to reflux for 2 h and then cooled. The excess ox-
alyl chloride was distilled off at atmospheric pressure and the remain-
ing material distilled under high vacuum.
2-[5-(Ethoxycarbonyl)pentanoyloxy]-4,6-dimethoxyphenyl 4-Meth-
oxybenzyl Ketone (8a): colourless oil; yield: 1.15 g (72%).
UV: λmax (log ε) = 216.2 (4.322), 269.6 nm (3.959).
IR (neat): νmax = 3200 (C=C–H), 1760 (C=O), 1630 cm–1 (C=C).
1H NMR: δ = 1.26 (t, 3H, J = 7.1 Hz, CO2CH2CH3), 1.68 (m, 4H, H-
3″, H-4″), 2.31 (t, 2H, J = 7.5 Hz, H-5″), 2.44 (t, 2H, J = 7.4 Hz, H-
2″), 3.78 (s, 3H, OCH3), 3.79 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 4.03
(s, 2H, H-8), 4.13 (q, 2H, J = 7.1 Hz, CO2CH2CH3), 6.21 (d, 1H, J =
2.2 Hz, H-5), 6.34 (d, 1H, J = 2.2 Hz, H-3), 6.84 and 7.11 (d, 4H, J =
8.7 Hz, H-2′, H-3′).
Ethyl 5-(Chlorocarbonyl)pentanoate (4a): colourless liquid; yield:
2.82 g (73%); bp 71–72°C/2 Torr.
IR: νmax = 2982 (C–H), 1800 (COCl), 1733 cm–1 (C=O ester).
1H NMR: δ = 1.22 (t, 3H, J = 6.7 Hz, OCH2CH3), 1.70 (q, 4H, J =
6.3 Hz, H-3, H-4), 2.28 (t, 2H, J = 8.7 Hz, H-5), 2.87 (t, 2H, J = 7.6
Hz, H-2), 4.16 (q, 2H, J = 6.7 Hz, CO2CH2CH3).
MS (CI): m/z (%) = 476 (M+ + NH4, 8), 459 (M+ + H, 36), 337 (6),
317 (4), 311 (5), 304 (12), 303 (68), 287 (56), 285 (20), 279 (10), 271
(8), 197 (11), 192 (23), 181 (40), 176 (53), 174 (67), 173 (100), 159
(57), 155 (90), 145 (47), 136 (36), 121 (38), 115 (7), 102 (7), 46 (13),
45 (30).
13C NMR: δ = 14.1 (CH3), 23.5 (C-4), 24.3 (C-3), 33.5 (C-5), 46.6 (C-
2), 60.3 (CH2O), 172.8 (CO2Et), 173.3 (COCl).
MS (CI): m/z (%) = 192 (M+, 23), 174 (100), 145 (32), 128 (35).
Methyl 5-(Chlorocarbonyl)pentanoate (4b): colourless liquid; yield:
2.67 g (94%); bp 61°C/0.1 Torr (lit.21 bp 62°C/0.1 Torr).
HRMS: obsd (MH+) 458.4953. Calcd for C25H30O8, 458.4947.
1H NMR: δ = 1.50–1.88 (m, 4H, H-3, H-4), 2.35 (t, 2H, J = 6.98 Hz,
H-5), 2.97 (t, 2H, J = 6.6 Hz, H-2), 3.11 (s, 3H, CO2CH3).
2,4-Dimethoxy-6-[5-(methoxycarbonyl)pentanoyloxy]phenyl
4-Methoxybenzyl Ketone (8b): colourless oil; yield: 1.14 g (62%).
UV: λmax (log ε) = 206.5 (4.373), 267.2 nm (3.907).
IR (neat): νmax = 2951 (C=C–H), 1763 (C=O), 1736 (C=O), 1613 cm–1
(C=C).
Methyl 8-(Chlorocarbonyl)octanoate (4c): colourless liquid; yield:
3.58 g (81%); bp 84°C/0.1 Torr (lit.22 bp 177°C/23 Torr).
1H NMR: δ = 1.28–1.42 (m, 6H, H-4, H-5, H-6), 1.58–1.64 (m, 2H,
H-7), 1.69–1.73 (m, 2H, H-3), 2.30 (t, 2H, J = 7.5 Hz, H-8), 2.89 (t,
2H, J = 7.6 Hz, H-2), 3.66 (s, 3H, CO2CH3).
1H NMR: δ = 1.46–1.83 (m, 4H, H-3″, H-4″), 2.32 (t, 2H, J = 7.4 Hz,
H-5″), 2.45 (t, 2H, J = 7.3 Hz, H-2″), 3.61 (s, 3H, CO2CH3), 3.71 (s,
3H, OCH3), 3.82 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 4.00 (s, 2H, H-
8), 6.20 (d, 1H, J = 2.2 Hz, H-5), 6.33 (d, 1H, J = 2.2 Hz, H-3), 6.84
and 7.11 (d, 4H, J = 8.7 Hz, H-2′, H-3′).
Butyl 8-(Chlorocarbonyl)octanoate (4d): colourless liquid; yield:
4.04 g (92%); bp 145°C/4 Torr.
MS (CI): m/z (%) = 462 (M+ + NH4, 11), 445 (M+ + H, 41), 414 (3),
385 (6), 329 (52), 301 (72), 295 (8), 165 (11), 164 (5), 159 (60), 155
(90), 121 (38), 102 (7), 46 (12), 45 (15).
1H NMR: δ = 0.93 [t, 3H, J = 7.0 Hz, CO2(CH2)2CH3], 1.33–1.40 (m,
8Η, 4 × CH2), 1.58–1.64 (m, 4H, 2 × CH2), 1.64–1.69 (m, 2H, CH2),
2.29 (t, 2H, J = 7.6 Hz, H-8), 2.89 (t, 2H, J = 7.3 Hz, H-2), 4.07 (t, 2H,
J = 6.7 Hz, OCH2Pr).
HRMS: obsd 444.5248. Calcd for C24H28O8, 444.5248.
13C NMR: δ = 13.7 (CH3), 19.2 (CH2CH3), 24.8 (C-5) 24.9 (C-4, C-
6), 28.1 (OCH2CH2), 28.7 (C-3), 29.1 (C-7), 34.3 (C-8), 46.9 (C-2),
64.2 (OCH2), 173.7 (CO2Bu), 173.9 (COCl).
2,4-Dimethoxy-6-[8-(methoxycarbonyl)octanoyloxy]phenyl 4-Meth-
oxybenzyl Ketone (8c): colourless oil; yield: 1.81 g (62%).
UV: λmax (log ε) = 203.5 (4.357), 269.1 nm (3.781).
MS (CI): m/z (%) = 262 (M+, 98), 242 (100), 187 (30), 170 (21).
HRMS: obsd 262.7765. Calcd for C13H23O3Cl, 262.7765.
IR (neat): νmax = 2937 (Ar C–H), 1731 (C=O), 1613 cm–1 (=C–H Ar).
1H NMR: δ = 1.32–1.36 (m, 6H, H-4″, H-5″, H-6″), 1.62–1.64 (m, 4H,
H-3″, H-7″), 2.28 (t, 2H, J = 7.6 Hz, H-8″), 2.41 (t, 2H, J = 7.8 Hz, H-
2″), 3.67 (s, 3H, CO2CH3), 3.78 (s, 3H, OCH3), 3.79 (s, 3H, OCH3),
3.83 (s, 3H, OCH3), 4.04 (s, 2H, H-8), 6.21 (d, 1H, J = 2.2 Hz, H-5),
6.34 (s, 1H, J = 2.2 Hz, H-3), 6.82 and 7.10 (d, 4H, J = 8.7 Hz, H-2′,
H-3′).
Methyl 9-(Chlorocarbonyl)nonanoate (4e): colourless liquid; yield:
4.42 g (94%); bp 158–160°C (lit.23 bp 158–160°C).
1H NMR: δ = 1.30–1.39 (m, 8H, H-4, H-5, H-6, H-7), 1.59–1.63 (m,
2H, H-8), 1.64–1.78 (m, 2H, H-3), 2.29 (t, 2H, J = 7.5 Hz, H-9), 2.87
(t, 2H, J = 7.3 Hz, H-2), 3.11 (s, 3H, CO2CH3).
MS (CI): m/z (%) = 487 (M+ + H, 100), 455 (23), 423 (4), 365 (11),
303 (92), 220 (29), 181 (71), 155 (12), 121 (5).
MS (EI): m/z (%) = 365 (15), 303 (4), 181 (100), 152 (4), 121 (16).
Butyl 9-(Chlorocarbonyl)nonanoate (4f): colourless liquid; yield:
4.25 g (83%); bp 165°C/4 Torr.
HRMS: obsd (MH+) 487.2332. Calcd for C27H35O8, 487.2332.
1H NMR: δ = 0.93 (t, 3H, J = 7.4 Hz, CH3), 1.30–1.39 (m, 10H, 5 ×
CH2), 1.57–1.63 (m, 4H, 2 × CH2), 1.64–1.72 (m, 2H, CH2), 2.29 (t,
2H, J = 7.6 Hz, H-9), 2.89 (t, 2H, J = 7.3 Hz, H-2), 4.07 (t, 2H, J = 6.7
Hz, OCH2Pr).
2-[8-(Butoxycarbonyl)octanoyloxy]-4,6-dimethoxyphenyl 4-Methoxy-
benzyl Ketone (8d): colourless oil; yield: 1.68 g (84%).
UV: λmax (log ε) = 204.0 (4.313), 285.6 (3.920), 324.2 nm (3.547).
IR (neat): νmax = 2936 (C=C–H), 1729 (C=O), 1612 cm–1 (C=C-Ar).
1H NMR: δ = 0.93 [t, 3H, J = 7.4 Hz, CO2(CH2)3CH3], 1.32–1.42 [m,
8H, H-4″, H-5″, H-6″, CO2(CH2)2CH2CH3], 1.59–1.64 (m, 6H, H-3″,
H-7″, CO2CH2CH2CH2CH3), 2.29 (t, 2H, J = 7.6 Hz, H-8″), 2.41 (t,
2H, J = 7.8 Hz, H-2″), 3.77 (s, 3H, OCH3), 3.78 (s, 3H, OCH3), 3.82
(s, 3H, OCH3), 4.04 (s, 2H, H-8), 4.07 (t, 2H, J = 6.7 Hz,
13C NMR: δ = 13.7 (CH3), 19.2 (CH2CH3), 23.1 (C-5, C-6), 23.3 (C-
4, C-7), 28.0 (OCH2CH2), 28.7 (C-3), 29.1 (C-8), 34.2 (C-9), 46.9 (C-
2), 64.4 (OCH2), 173.8 (CO2Bu), 174.1 (COCl).
MS (CI): m/z (%) = 276 (M+, 67), 256 (50), 207 (35), 187 (21), 184
(23).
HRMS: obsd 276.8049. Calcd for C14H25O3Cl, 276.8049.