Mar-Apr 2008
Synthesis of Novel Aromatic Macrolactones
441
eq) in 30 mL DCM was added via syringe through a pierced
rubber septum. A separate RBF, equipped for magnetic stirring
was similarly flame-dried under nitrogen. After cooling to room
temperature, the flask was charged with the starting carboxylic
acid (1.00 eq) and 1.5 equivalents of SOCl2. The mixture was
stirred for 1.5 hours while maintaining the flow of nitrogen, after
which the excess SOCl2 was evaporated in vacuo. The resulting
acid chloride was re-dissolved in 30 mL dry DCM and
transferred via syringe to the dropping funnel, and subsequently
added drop-wise over 10 minutes with stirring to the phenol
133, 105, 92, 77, 64, 41. Anal. Calcd. for C20H18O5 (338.35): C,
70.99; H, 5.36. Found: C, 70.90: H, 5.25.
2-[3-(Allyloxy)-3-oxopropyl]phenyl 2-allyloxybenzoate (19).
Compound 19 was isolated as a clear oil after chromatography
(64%); ir: 750, 924, 1102, 1216, 1441, 1584, 1599, 1737, 2849,
2919, 3016, 3076 cm-1; 1H nmr (CDCl3, ppm): δ 2.70 (t, J = 8.1
Hz, 2H); 3.00 (t, J = 7.5 Hz, 2H); 4.56 (d, J = 5.5 Hz, 2H); 4.70 (d,
J = 4.6 Hz, 2H); 5.20 (d, J = 10.4 Hz, 1H); 5.26 (d, J = 16.2 Hz,
1H); 5.29 (d, J = 9.1 Hz, 1H); 5.52 (d, J = 17.2 Hz, 1H); 5.88 (ddt,
J = 4.9, 10.5, 17.1 Hz, 1H); 6.10 (ddt, J = 5.7, 10.5, 17.0 Hz, 1H);
7.05 (d, J = 8.2 Hz, 1H); 7.08 (t, J = 7.4 Hz, 1H); 7.22 (m, 2H);
7.32 (m, 2H); 7.55 (dt, J = 1.6, 8.1 Hz, 1H); 8.05 (dd, J = 1.4, 7.6
Hz, 1H); 13C nmr (CDCl3, ppm): δ 26.1, 34.9, 65.5, 69.9, 114.0,
118.2, 118.5, 119.9, 120.9, 123.1, 123.1, 126.5, 128.0, 130.6,
132.6, 132.7, 132.9, 133.0, 134.6, 149.7, 159.1, 165.0, 172.9; ms:
m/z 366 (M+), 219, 189, 178, 160, 147, 121, 91, 77, 65, 55, 41
(100%). Anal. Calcd. for C22H22O5 (366.41): C, 72.12; H, 6.05.
Found: C, 72.13; H, 6.01.
Allyl 2-({3-[2-allyloxyphenyl]propanoyl}oxy)benzoate (20).
Compound 20 was isolated as a clear oil after chromatography
(53%); ir: 753, 928, 1135, 1453, 1493, 1606, 1725, 1758, 2848,
2918, 3016, 3076 cm-1; 1H nmr (CDCl3, ppm): δ 2.99 (t, J = 7.0
Hz, 2H); 3.14 (t, J = 7.0 Hz, 2H); 4.62 (d, J = 4.6 Hz, 2H); 4.78
(d, J = 4.5 Hz, 2H); 5.31 (m, 2H); 5.42 (dd, J = 1.3, 17.2 Hz,
1H); 5.48 (dd, J = 1.3, 17.3 Hz, 1H); 6.03 (ddt, J = 5.6, 10.4,
17.0 Hz, 1H); 6.13 (ddt, J = 5.0, 10.6, 17.2 Hz, 1H); 6.89 (d, J =
8.0 Hz, 1H); 6.94 (t, J = 6.8 Hz, 1H); 7.05 (d, J = 7.8 Hz, 1H);
7.27 (m, 2H); 7.33 (t, J = 7.4 Hz, 1H); 7.57 (dt, J = 0.8, 7.3 Hz,
1H); 8.06 (dd, J = 1.3, 7.7 Hz, 1H); 13C nmr (CDCl3, ppm):
δ 26.4, 34.5, 66.1, 69.0, 111.9, 117.4, 119.1, 121.1, 123.9, 124.3,
126.3, 128.0, 129.3, 130.7, 132.2, 132.4, 133.8, 134.2, 151.1,
156.9, 164.7, 172.4. Anal. Calcd. for C22H22O5 (366.41): C,
72.12; H, 6.05. Found: C, 72.28; H, 6.10.
solution.
Stirring was continued for 12 hours at room
temperature, after which the reaction mixture was transferred to
an RBF and the solvent evaporated in vacuo to give the crude
product as a yellow solid. The crude material was subsequently
extracted with two 30 mL portions of ether, decanting the two
liquid phases. The combined ether solutions were evaporated in
vacuo, and the residue chromatographed on silica gel using
hexanes:ethyl acetate; 3:1 as eluent to give the pure diene.
3-(Allyloxycarbonyl)phenyl 3-allyloxybenzoate (16).
Compound 16 was obtained as
a
clear solid after
chromatography (62%), mp 34 °C; ir: 748, 933, 1100, 1260,
1441, 1486, 1586, 1648, 1725, 2850, 2918, 3079 cm-1; 1H nmr
(CDCl3, ppm): δ 4.65 (d, J = 4.9 Hz, 2H); 4.87 (d, J = 5.4 Hz,
2H); 5.32 (d, J = 11.0 Hz, 1H); 5.35 (d, J = 10.7 Hz, 1H); 5.44
(d, J = 17.0 Hz, 1H); 5.48 (d, J = 16.0 Hz, 1H); 6.08 (m, 2H);
7.24 (d, J = 6.0 Hz, 1H); 7.45 (m, 2H); 7.54 (t, J = 7.8 Hz, 1H);
7.74 (s, 1H), 7.84 (d, J = 7.3 Hz, 1H); 7.93 (s, 1H); 8.02 (d, J =
7.5 Hz, 1H). 13C nmr (CDCl3, ppm): δ 66.3, 69.4, 115.9, 118.5,
119.0, 121.4, 123.2, 123.4, 126.9, 127.6, 129.9, 130.1, 130.8,
132.2, 132.4, 133.1, 151.3, 159.1, 165.2, 165.7; ms: m/z 338
(M+), 281, 161 (100%), 133, 105, 77, 65, 55, 41. Anal. Calcd.
for C20H18O5 (338.35): C, 70.99; H, 5.36. Found: C, 70.99; H,
5.32.
2-[3-Allyloxy-3-oxopropyl]phenyl 3-allyloxybenzoate (17).
Compound 17 was obtained as a clear oil after chromatography
(64%); ir: 750, 924, 1102, 1216, 1441, 1489, 1584, 1593, 1737,
2917, 3016, 3076 cm-1; 1H nmr (CDCl3, ppm): δ 2.69 (t, J = 7.6
Hz, 2H); 2.97 (t, J = 7.4 Hz, 2H); 4.56 (d, J = 4.8 Hz, 2H); 4.65
(d, J = 3.9 Hz, 2H); 5.20 (d, J = 10.4 Hz, 1H); 5.26 (d, J = 17.3
Hz, 1H); 5.35 (d, J = 10.5 Hz, 1H); 5.48 (d, J = 17.3 Hz, 1H);
5.86 (ddt, J = 5.4, 10.7, 16.3 Hz, 1H); 6.10 (ddt, J = 4.9, 11.0,
16.2 Hz, 1H); 7.27 (m, 5H); 7.45 (t, J = 7.8 Hz, 1H); 7.76 (s,
1H), 7.85 (d, J = 7.4 Hz, 1H); 13C nmr (CDCl3, ppm): δ 26.0,
34.9, 65.6, 69.4, 115.9, 118.5, 118.6, 121.4, 122.9, 123.1, 126.7,
128.1, 130.1, 130.6, 131.0, 132.5, 132.9, 133.2, 149.6, 159.2,
165.3, 172.7; ms: m/z 366 (M+), 348, 206, 161 (100%), 133,
105, 92, 79, 64, 41. Anal. Calcd. for C22H22O5 (366.41): C,
72.12; H, 6.05. Found: C, 72.19; H, 6.06.
2-(Allyloxycarbonyl)phenyl 2-allyloxybenzoate (18). Compound
18 was obtained as a clear solid after chromatography (59%), mp
59 °C; ir: 750, 1199, 1252, 1449, 1487, 1601, 1724, 1747, 2850,
2918, 2983, 3016, 3076 cm-1; 1H nmr (CDCl3, ppm): δ 4.68 (dd, J
= 1.3, 3.2 Hz, 1H); 4.72 (dd, J = 0.8, 5.6 Hz, 2H); 5.16 (d, J = 10.3
Hz, 1H); 5.27 (dd, J = 1.3, 16.4 Hz, 1H); 5.29 (dd, J = 1.5, 12.2
Hz, 1H); 5.54 (d, J = 17.2 Hz, 1H); 5.87 (ddt, J = 5.7, 11.0, 16.5
Hz, 1H); 6.08 (ddt, J = 4.7, 10.7, 15.7 Hz, 1H); 7.03 (d, J = 8.4 Hz,
1H); 7.08 (t, J = 7.6 Hz, 1H); 7.26 (d, J = 8.1 Hz, 1H); 7.37 (t, J =
7.6 Hz, 1H); 7.54 (dt, J = 1.6, 7.4 Hz, 1H); 7.62 (dt, J = 1.5, 7.5
Hz, 1H); 8.10 (d, J = 7.7 Hz, 1H); 8.16 (d, J = 7.7 Hz, 1H); 13C
nmr (CDCl3, ppm): δ 66.2, 69.9, 114.0, 118.0, 119.0, 119.7, 120.9,
124.2, 124.6, 126.3, 132.2, 132.3, 133.0, 133.2, 134.2, 134.6,
151.2, 159.4, 164.4, 164.8; ms: m/z 338 (M+), 178, 161 (100%),
2-(3-Allyloxy-3-oxopropyl)phenyl 3-(2-allyloxyphenyl)
propanoate (21). Compound 21 was isolated as a clear oil after
chromatography (55%); ir: 753, 928, 1171, 1492, 1601, 1648,
1737, 1755, 2862, 2918, 3021, 3076 cm-1; 1H nmr (CDCl3,
ppm): δ 2.58 (t, J = 7.8 Hz, 2H); 2.82 (t, J = 7.4 Hz, 2H); 2.96 (t,
J = 7.7 Hz, 2H); 3.14 (t, J = 7.4 Hz, 2H); 4.58 (d, J = 5.5 Hz,
2H); 4.62 (d, J = 4.6 Hz, 2H); 5.23 (d, J = 10.3 Hz, 1H); 5.29 (d,
J = 17.2 Hz, 1H); 5.31 (d, J = 9.9 Hz, 1H); 5.47 (d, J = 17.2 Hz,
1H); 5.90 (ddt, J = 5.6, 10.7, 16.7 Hz, 1H); 6.11 (ddt, J = 4.8,
10.8, 16.9 Hz, 1H); 6.88 (d, J = 8.1 Hz, 1H); 6.93 (d, J = 7.4 Hz,
1H); 6.98 (d, J = 7.8 Hz, 1H); 7.21 (m, 5H); 13C nmr (DMSO,
ppm): δ 25.5, 26.4, 34.2, 34.4, 65.3, 68.9, 112.8, 117.5, 118.6,
121.3, 123.3, 126.9, 128.3, 128.6, 128.9, 130.5, 130.9, 133.1,
133.5, 134.7, 149.6, 156.9, 172.1, 172.5. Anal. Calcd. For
C24H26O5 (394.46): C, 73.08; H, 6.64. Found: C, 73.12; H, 6.61.
2-Methylallyl-3-{[2-(2-allyloxyphenyl)propanoyl]oxyphen-
yl}propanoate (22). Compound 22 was isolated as a clear oil
after chromatography (56%); ir: 753, 923, 1171, 1453, 1492,
1587, 1601, 1738, 1755, 2917, 2967, 3021, 3071 cm-1; 1H nmr
(CDCl3, ppm): δ 1.73 (s, 3H); 2.60 (t, J = 8.2 Hz, 2H); 2.83 (t, J
= 7.5 Hz, 2H); 2.96 (t, J = 8.0 Hz, 2H); 3.14 (t, J = 7.4 Hz, 2H);
4.50 (s, 2H); 4.61 (m, 2H); 4.92 (s, 1H); 4.95 (s, 1H); 5.30 (dd, J
= 1.5, 10.6 Hz, 1H); 5.47 (dd, J = 1.6, 17.3 Hz, 1H); 6.10 (ddt, J
= 4.9, 10.6, 17.3 Hz, 1H); 6.88 (d, J = 8.1 Hz, 1H); 6.92 (dt, J =
0.9, 7.5 Hz, 1H); 6.99 (dd, J = 1.1, 8.0 Hz, 1H); 7.20 (m, 5H);
C nmr (CDCl3, ppm): δ 19.9, 25.9, 26.8, 34.5, 34.7, 68.2,
69.0, 111.9, 113.3, 117.4, 121.1, 122.9, 126.5, 128.0, 128.2,
129.0, 130.5, 130.7, 132.7, 133.8, 140.3, 149.4, 156.9, 172.2,
172.8; ms: m/z 188, 160, 145 (100%), 131, 120, 105, 91, 78, 57,