Engineering Reactions in Crystalline Solids
J . Org. Chem., Vol. 66, No. 13, 2001 4475
which was purified by flash chromatography (hexane/ethyl
41.18, 41.22, 41.29, 42.51, 43.90, 80.24, 80.47, 173.89, 174.35.
IR (KBr): 2912, 2852, 1728, 1455, 1245, 1053. EI HRMS: calcd
for C26H38O4 414.2770, found 414.2774.
acetate ) 9:1) to give 0.35 g white solid 1d in 90% yield, mp
1
93-95 °C. H NMR: δ 1.33 (s, 3H), 1.35 (d, J ) 7.2 Hz,3H),
1.41 (s, 3H), 1.65 (br, 12H), 2.07 (br, 12H), 2.16 (br, 6H), 3.75
(q, 1H). 13C NMR: δ 15.39, 21.93, 22.16, 30.79, 30.84, 36.05,
36.07, 41.09, 49.53, 57.21, 81.81, 81.99, 169.04, 172.06, 204.58.
IR (KBr): 2914, 2853, 1738, 1731, 1712, 1455, 1251, 1156,
1054. EI HRMS: calcd for C28H40O5 456.2876, found 456.2860.
Dia d a m a n tyl Su ccin a te (2a ). To a solution of succinic
anhydride (0.2 g, 2 mmol) in toluene was added 1-adamantanol
(0.73 g, 4.8 mmol), followed by a catalytic amount of p-
toluenesulfonic acid. The resulting mixture was heated to
reflux with a Dean-Stark apparatus overnight. The reaction
mixture was washed with 5% sodium bicarbonate and ex-
tracted with ethyl acetate (three times). The combined organic
layers were washed with brine, dried over anhydrous MgSO4,
and concentrated to give a crude white solid. Excess 1-ada-
mantanol was removed by sublimation to give 0.69 g of diester
2a in 89% yield. 1H NMR: δ 1.60 (br,12H), 2.05 (br, 12H), 2.10
(br, 6H), 2.42 (s,4H). 13C NMR: δ 30.79, 36.17, 41.26, 44.98,
80.46, 171.35. IR (KBr): 2985, 2914, 1740, 1374, 1242, 1048.
EI HRMS: calcd for C24H34O4 386.2457, found 386.2462.
Meth yl Dia d a m a n tyl Su ccin a te (2b). To a solution of
methyl succinic acid (0.16 g, 1.2 mmol) in toluene was added
1-adamantanol (0.48 g, 3.1 mmol), followed by a catalytic
amount of p-toluenesulfonic acid. The resulting mixture was
heated to reflux with a Dean-Stark apparatus overnight. The
reaction mixture was washed with 5% sodium bicarbonate and
extracted with ethyl acetate (three times). The combined
organic layers were washed with brine, dried over anhydrous
MgSO4, and concentrated to give a crude white solid. Excess
1-adamantanol was removed by sublimation to give 0.43 g of
Ad a m a n tyl Aceta te (3a ). To a solution of 1-adamantanol
(0.19 g, 1.2 mmol) in 4 mL of CH2Cl2 were added acetyl chloride
(0.13 mL, 1.8 mmol) and pyridine (0.5 mL). The resulting
solution was stirred overnight at room temperature. Aqueous
sodium bicarbonate (5%) was added, and the aqueous layer
was extracted twice with diethyl ether. The combined organic
layers were washed with brine, dried over anhydrous MgSO4,
and concentrated in vacuo to give 0.21 g of ester 3a in 90%
yield. 1H NMR: δ 1.60(br, 6H), 1.91 (s, 3H), 2.05 (br, 6H), 2.09
(br, 3H).13C NMR: δ 22.60, 30.66, 36.06, 41.15, 80.19, 170.24.
IR (neat): 2912, 2853, 1732, 1457, 1244, 1060. EI HRMS: calcd
for C12H18O2 194.1307, found 194.1306.
Ad a m a n tyl P r op ion a te (3b). To a solution of 1-adaman-
tanol (0.24 g, 1.6 mmol) in CH2Cl2 (5 mL) were added propionyl
chloride (0.3 mL) and pyridine (0.8 mL). The resulting solution
was stirred overnight at room temperature. Aqueous sodium
bicarbonate (5%) was added, and the aqueous layer was
extracted twice with diethyl ether. The combined organic
layers were washed with brine, dried over anhydrous MgSO4,
and concentrated in vacuo to give 0.3 g of ester 3b in 92% yield.
1H NMR: δ 0.89 (t, 3H), 1.48 (br, 6H), 1.93 (br, 6H), 1.97 (br,
3H), 2.04 (q, 2H). 13C NMR: δ 9.07, 28.72, 30.65, 36.08, 41.18,
79.76, 173.49. IR (neat): 2913, 2858, 1731, 1242, 1196, 1057.
EI HRMS: calcd for C13H20O2 208.1463, found 208.1459.
Ad a m a n tyl Acr yla te (4a ). To a solution of 1-adamantanol
(0.18 g, 1.2 mmol) in CH2Cl2(4 mL) were added acryloyl
chloride (0.3 mL) and pyridine(0.5 mL). The resulting solution
was stirred overnight at room temperature. Aqueous sodium
bicarbonate (5%) was added, and the aqueous layer was
extracted twice with diethyl ether. The combined organic
layers were washed with brine, dried over anhydrous MgSO4,
and concentrated in vacuo to give 0.22 g of ester 4a in 90%
yield. 1H NMR: δ 1.57 (br, 6H), 2.05 (br, 9H), 5.61 (dd, J )
1.6, 10.3 Hz, 1H), 5.91 (dd, J ) 10.3, 17.3 Hz, 1H), 6.17 (dd, J
) 1.6, 17.3 Hz, 1H). 13C NMR: δ 30.74, 36.07, 41.21, 80.39,
129.10, 130.38, 165.06. IR (neat): 2912, 2853, 1720, 1636,
1457, 1402, 1198, 1058. EI HRMS: calcd for C13H18O2 206.1307,
found 206.1297.
1
diester 2b in 90% yield. H NMR: δ 1.07 (d, J ) 7.2 Hz, 3H),
1.64 (br, 6H), 1.65 (br, 6H), 2.02 (br, 6H), 2.03 (br, 6H), 2.05
(br, 6H), 2.17 (dd, J ) 14.4, 7.2 Hz, 1H), 2.50 (dd J ) 14.4, 7.2
Hz, 1H), 2.62-2.68 (m, 1H). 13C NMR: δ 16.95, 30.68, 30.76,
36.14, 36.16, 36.95, 39.08, 41.17, 41.25, 80.20, 80.48, 170.91,
174.36. IR (KBr): 2910, 2851, 1729, 1455, 1276, 1170, 1056.
EI HRMS: calcd for C25H36O4 400.2614, found 400.2604.
2,3-Dim eth yl Dia d a m a n tyl Su ccin a te (2c). To a solution
of 2,3-dimehtyl succinic acid (0.18 g, 1.2 mmol) in toluene was
added 1-adamantanol (0.48 g, 3.1 mmol), followed by catalytic
amount of p-toluenesulfonic acid. The resulting mixture was
heated to reflux with a Dean-Stark apparatus overnight. The
reaction mixture was washed with 5% sodium bicarbonate and
extracted with ethyl acetate (three times). The combined
organic layers were washed with brine, dried over anhydrous
MgSO4, and concentrated to give a crude white solid. Excess
1-adamantanol was removed by sublimation to give 0.46 g of
Ack n ow led gm en t. This work was supported by the
NSF (grants DMR9988439 and CHE0073431). Solid
state NMR spectra were acquired with equipment
purchased with NSF grant DMR9975975. Support by
Merck Pharmaceutical Co. is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Full 13C NMR spec-
tra of all new compounds. This material is available free of
1
diester 2c in 92% yield. H NMR: δ 0.98 (d, J ) 3.6 Hz, 3H),
1.03 (d, J ) 3.6 Hz, 3H), 1.64 (br, 12H), 1.65 (br, 12H), 2.02
(br, 24H), 2.06 (br, 12H), 2.42-2.45 (m, 2H), 2.56-2.60 (m,
2H). 13C NMR: δ 13.26, 15.33, 30.79, 36.04, 36.18, 36.20, 41.13,
J O005747M