5836 J . Org. Chem., Vol. 65, No. 18, 2000
Notes
reaction mixture, 8 mL of 0.25 N NaOH was added in small
portions with stirring until the consumption of the starting
diester was detected by thin-layer chromatography. The reaction
was stirred at the same temperature for about 30 min to 1 h,
and the reaction mixture was acidified with 1 N HCl at 0 °C,
saturated with NaCl, extracted with ethyl acetate three to four
times, and dried with sodium sulfate. This extract was evapo-
rated in vacuo and purified by silica gel column chromatography
to afford the desirable half-esters. The typical eluent for column
chromatography was ethyl acetate to elute the pure half-ester.
Half-Ester 1b. 1H NMR (300 MHz, CDCl3) δ ) 2.6-2.7 (4H,
m), 3.62 (3H, s), 9.9 (1H, br.s); 13C NMR (75 MHz, CDCl3) δ )
28.54, 28.86, 51.91, 172.64, 178.34; IR (neat, cm-1) 1710, 1729,
2600-3990; mp 55-56 °C.9 Anal. Calcd for C5H8O4: C, 45.46;
H, 6.10. Found: C, 45.61; H, 6.05.
(neat, cm-1) 1720, 1730, 2670-3000; mp 140 °C (optically active
6b obtained by pig liver esterase is reported to be 140-141.5
°C).12 Anal. Calcd for C13H16O6: C, 58.20; H, 6.01. Found: C,
58.00; H, 5.83.
Gen er a l P r oced u r e for Mon oh yd r olysis of Sym m etr ic
Dieth yl Ester s. Diester (0.9 mmol) was dissolved in 2 mL of
THF, and 20 mL of water was added. The reaction mixture was
immersed in an ice-water bath and cooled to 0 °C. To this
reaction mixture, 24 mL of 0.25 N NaOH was added in small
portions with stirring until the consumption of the starting
diester was detected by thin-layer chromatography. The reaction
was stirred at the same temperature for about 30 min to 1 h,
and the reaction mixture was acidified with 1 N HCl at 0 °C,
saturated with NaCl, extracted with ethyl acetate three to four
times, and dried with sodium sulfate. This extract was evapo-
rated in vacuo and purified by silica gel column chromatography
to afford the desirable half-esters. The typical eluent for column
chromatography ethyl acetate to elute the pure half-ester.
Half-Ester 2b. 1H NMR (300 MHz, CDCl3) δ ) 3.80 (3H, s),
6.81 (1H, d, J ) 18.0 Hz), 6.90 (1H, d, J ) 18.0 Hz), 11.2 (1H,
br.s); 13C NMR (75 MHz, acetone-d6) δ ) 52.6, 134.0, 134.7,
165.9, 166.1; IR (neat, cm-1) 1720, 1710, 2940-3000; mp 141-
141.5 °C (lit. 141-141.5 °C).10 Anal. Calcd for C5H6O4: C, 46.16;
H, 4.65. Found: C, 45.82; H, 4.73.
1
Half-Ester 7b. H NMR (300 MHz, CDCl3) δ ) 1.25 (3H, t, J
) 7.2 Hz), 4.2 (2H, m), 4.66 (1H, s), 7.3 (5H, m), 10.9 (1H, br.s
(-COOH)); 13C NMR (75 MHz, CDCl3) δ ) 13.82, 57.50, 62.11,
128.39, 128.63, 129.13, 132.02, 167.97, 173.75; IR (neat, cm-1
)
Half-Ester 3b. 1H NMR (300 MHz, CDCl3) δ ) 3.92 (3H, s),
6.39 (1H, d, J ) 12.6 Hz), 6.49 (1H, d, J ) 12.6 Hz), 9.8 (1H,
br.s (-COOH)); 13C NMR (75 MHz, CDCl3) δ ) 53.35, 129.51,
135.01, 165.57, 167.74; IR (neat, cm-1) 1720, 1740, 2940-3060.
HRMS Calcd for C5H16O4N(M+NH4)+: 148.0610. Found:
148.0607.
1711, 1739, 2660-2990; mp 77 °C (lit. 76-77 °C).1a Anal. Calcd
for C11H12O4: C, 63.45; H, 5.81. Found: C, 63.16; H, 5.66.
1
Half-Ester 8b. H NMR (300 MHz, CDCl3) δ ) 1.50 (3H, t, J
) 7.2 Hz), 2.19 (1H, d, J ) 10.0 Hz), 2.30 (1H, d, J ) 10.0 Hz),
4.16 (1H, br.s), 4.28 (1H, br.s), 4.4 (2H, m), 6.9 (2H, m); 13C NMR
(75 MHz, CDCl3) δ ) 13.88, 53.34, 54.68, 63.31, 72.63, 141.71,
142.67, 151.37, 162.10, 162.64, 167.73; IR (neat, cm-1) 1710,
1729, 2650-2980. HRMS Calcd for C11H12O4(M+): 208.0735.
Found: 208.0736.
1
Half-Ester 4b. H NMR (300 MHz, CDCl3) δ ) 2.14 (1H, d, J
) 10.2 Hz), 2.25 (1H, d, J ) 10.2 Hz), 3.96 (3H, s), 4.12 (1H, s),
4.25 (1H, s), 6.92 (2H, m);13C NMR (75 MHz, CDCl3) δ ) 53.31,
53.69, 54.64, 72.62, 141.71, 142.58, 150.99, 162.25, 162.49,
168.11; IR (neat, cm-1) 1711, 1730, 2650-3980; mp 107 °C (lit.
108-109 °C).11 HRMS Calcd for C10H11O4(M+H)+: 195.0657.
Found: 195.0657.
1
Half-Ester 9b. H NMR (300 MHz, CDCl3) δ ) 1.48 (3H, t, J
) 7.2 Hz), 1.57 (1H, d, J ) 11.2 Hz), 1.78 (1H, d, J ) 11.2 Hz),
3.53 (1H, br.s), 3.6 (2H, m), 3.74 (1H, br.s), 4.4 (2H, m); 13C NMR
(75 MHz, CDCl3) δ ) 13.90, 38.51, 47.15, 48.08, 57.80, 57.80,
63.78, 148.40, 158.78, 162.23, 167.40; IR (neat, cm-1) 1710, 1728,
2650-2980. HRMS calcd for C11H16O5N(M+NH4)+: 242.1029.
Found: 242.1029.
1
Half-Ester 5b. H NMR (300 MHz, CDCl3) δ ) 1.56 (1H, d, J
) 12 Hz), 1.79 (1H, d, J ) 12 Hz), 3.50 (1H, br.s), 3.6 (2H, m),
3.69 (1H, br.s), 3.95 (3H, s), 9.7 (1H, br.s (-COOH)); 13C NMR
(75 MHz, CDCl3) δ ) 38.48, 47.07, 47.95, 53.99, 57.68, 57.71,
148.11, 158.49, 162.23, 167.71; IR(cm-1) 1713, 1725, 2650-3980.
HRMS calcd for C10H11O5(M+H)+: 211.0606. Found: 211.0596.
Half-Ester 6b. 1H NMR (300 MHz, CDCl3) δ ) 1.35 (3H, s),
1.51 (3H, s), 1.90 (1H, br.d, J ) 10.0), 2.07 (1H, d, J ) 10.0 Hz),
3.67 (1H, br.s), 3.53(1H, br.s), 3.94 (3H, s), 4.39 (2H, br.s); 13C
NMR (75 MHz, CDCl3) δ) 24.38, 25.79, 41.15, 49.35, 50.41,
53.99, 79.44, 79.64, 114.70, 142.84, 153.51, 161.54, 167.53; IR
Ack n ow led gm en t . The author thanks Oklahoma
State University, College of Arts and Sciences for
financial support (start-up funds).
Su p p or tin g In for m a tion Ava ila ble: Copies of 13C NMR
spectra of 3b-5b, 8b, and 9b. This material is available free
(9) Half-ester 1b is a known compound, but the melting point was
not found.
J O0001986
(10) Dymickey, M.; Buchanan, R. L. Org. Prep. Proced. Int. 1985,
17, 121.
(11) Metz, P. Tetrahedron 1989, 45, 7311.
(12) Arita, M.; Adachi, K.; Ito, Y.; Sawai, H.; Ohno, M. J . Am. Chem.
Soc. 1983, 105, 4049.