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B. A. Kulkarni et al.
PAPER
dehyde 4 (2.0 g, 0.024 mol) in THF (30 mL) was added dropwise to
the solution at 0 °C. Stirring was continued at r.t. for 24 h. The mix-
ture was poured in ice-cooled water, extracted with hexane, the or-
ganic layer washed thoroughly with H2O and brine, and
concentrated in vacuo. The residue was re-dissolved in hexane,
cooled to 0 °C, the solution filtered and the precipitate washed with
cold hexane. The hexane solution was concentrated again in vacuo
and the residue subjected to column chromatography (silica gel,
hexane) to furnish 6; yield: 3.63 g (49%).
IR (film): 3320, 3010, 2100, 1660 cm–1.
1H NMR: = 0.9 (dist. t, 3 H), 1.32 (br s, 28 H), 2.1–2.5 (m, 7 H),
5.3–5.5 (m, 2 H).
IR (film): 3380, 3010, 1660 cm–1.
1H NMR: = 0.89 (dist t, 3 H), 1.37 (br s, 30 H), 1.9–2.3 (m, 8 H),
2.5 (s, D2O exchangeable, 1 H), 3.68 (t, J = 6 Hz, 2 H), 5.2–5.5 (m,
4 H).
Anal. Calcd for C25H48O: C, 82.34; H, 13.27. Found: C, 82.59; H,
13.48.
(4Z,8Z)-Pentacosa-4,8-dienal (10)
As described earlier, compound 9 (2.7 g, 7.42 mmol) was oxidized
with PCC (2.40 g, 11.14 mmol) in CH2Cl2 (30 mL) to give aldehyde
10; yield: 2.15 g (80%).
IR (film): 3010, 2720, 1730, 1660 cm–1.
Anal. Calcd for C22H40: C, 86.76; H, 13.24. Found: C, 86.95; H,
13.44.
1H NMR: = 0.89 (dist. t, 3 H), 1.34 (br s, 28 H), 2.16–2.32 (m, 8
H), 2.39–2.45 (m, 2 H), 5.2–5.5 (m, 4 H), 9.78 (t, J = 1.5 Hz, 1 H).
Anal. Calcd for C25H46O: C, 82.80; H, 12.79. Found: C, 82.72; H,
12.94.
3-Bromo-1-tetrahydropyranyloxypropane (7)
Following a reported procedure,16 propane-1,3-diol (15.0 g, 0.197
mol) was monobrominated with 48% aq HBr (33.30 mL, 0.197 mol)
in C6H6 (200 mL) to give the bromohydrin; yield: 18.89 g (69%).
(5Z,9Z)-2-Hydroxyhexacosa-5,9-dienenitrile (11)
To a stirred solution of NaHSO3 (0.775 g, 7.45 mmol) in H2O (10
mL) was added aldehyde 10 (1.8 g, 4.97 mmol) in CH2Cl2 (30 mL).
Immediately a white crystalline solid formed which was dissolved
by adding H2O (10 mL). To this solution was slowly added NaCN
(0.365 g, 7.45 mmol) in H2O (10 mL) so that the reaction tempera-
ture maintained at 0–5 °C. After stirring for 16 h at r.t. (cf. TLC),
the mixture was extracted with CHCl3, the organic layer washed
with H2O and brine, and dried. The residue obtained on concentra-
tion in vacuo was purified by column chromatography (silica gel,
EtOAc–hexane, 0–15%) to give 11; yield: 1.2 g (62%).
A solution of the above compound (18.0 g, 0.129 mol), dihydropy-
ran (DHP) (10.88 g, 0.129 mol) and pyridinium p-toluenesulfonate
(PPTS, 0.1 g) in CH2Cl2 (200 mL) was stirred at r.t. for 6 h. The re-
action was quenched with 10% aq NaHCO3, the organic layer sep-
arated and the aqueous portion extracted with CHCl3. The
combined organic extracts were washed with H2O and brine, and
dried. Removal of the solvent followed by column chromatography
(silica gel, Et2O–hexane, 0–5%) of the residue gave pure 7;11 yield:
25.02 g (87%).
IR (film): 1085, 1020, 990, 810 cm–1.
1H NMR: = 1.2–1.3 (m, 2 H), 1.6–1.9 (m, 6 H), 3.2–3.8 (m, 6 H),
4.6 (br s, 1 H).
IR (film): 3420, 3020, 2220, 1660 cm–1.
1H NMR: = 0.88 (dist. t, 3 H), 1.36 (br s, partially D2O exchange-
able, 31 H), 2.1–2.4 (m, 8 H), 4.32 (t, J = 6 Hz, 1 H), 5.3–5.5 (m, 4
H).
(8Z)-Pentacos-8-en-4-yn-1-ol (8)
Anal. Calcd for C26H47NO: C, 80.14; H, 12.16; N, 3.59. Found: C,
80.29; H, 12.24; N, 3.43.
To a stirred and cooled (–25 °C) solution of 6 (3.5 g, 0.012 mol) in
THF (30 mL) was added n-BuLi (7.7 mL, 1.5 M in hexane, 0.012
mol). After 0.5 h, HMPA (5 mL) was added at –78 °C, the mixture
stirred for 15 min and bromide 7 (2.68 g, 0.012 mol) in THF (20
mL) was added. Stirring was continued at the same temperature for
4 h and at r.t. for 16 h. The mixture was poured in ice-cooled water,
extracted with Et2O, the organic layer washed with H2O and brine,
and concentrated in vacuo. The crude product was dissolved in
MeOH (30 mL), p-toluenesulfonic acid (PTS, 0.05 g) was added
and the solution was refluxed for 4 h. Most of the solvent was re-
moved in vacuo, the residue taken up in Et2O and washed with 10%
aq NaHCO3, H2O and brine, and dried. Removal of the solvent fol-
lowed by column chromatography (silica gel, EtOAc–hexane, 0–
15%) of the residue gave pure 8; yield: 2.93 g (70%).
(5Z,9Z)-2-Hydroxyhexacosa-5,9-dienoic Acid (12)
A solution of 11 (1.2 g, 3.08 mmol) and concd HCl (8.0 mL) was
stirred for 16 h at r.t. and at 80 °C for 8 h. The residue was extracted
with Et2O, the extract was carefully washed with ice-cold water and
brine, and dried. Removal of the solvent followed by column chro-
matography (silica gel, EtOAc–hexane, 0–10%) of the residue gave
12; yield: 1.14 g (91%); mp 83–85 °C (Et2O).
IR: 3700–3500, 3380, 1710 cm–1.
1H NMR: = 0.9 (dist. t, 3 H), 1.29 (br s, 30 H), 1.9–2.2 (m, 8 H),
2.6 (br s, D2O exchangeable, 1 H), 4.45 (t, J = 6 Hz, 1 H), 5.2–5.4
(m, 4 H), 8.9 (br s, D2O exchangeable, 1 H).
IR (film): 3440, 3010, 1660 cm–1.
1H NMR: = 0.9 (dist t, 3 H), 1.38 (br s, partially D2O exchange-
able, 31 H), 2.14–2.32 (m, 4 H), 2.42–2.63 (m, 4 H), 3.65 (t, J = 6
Hz, 2 H), 5.3–5.5 (m, 2 H).
(2S,5Z,9Z)-2-(Acetyloxy)hexacosa-5,9-dienoic Acid (13)
A slurry of (+)-12 (0.816 g, 2.0 mmol) and column grade silica gel
(2.0 g) in Et2O (10 mL) was shaken and the solvent evaporated in
vacuo. A mixture of the resultant immobilized substrate, vinyl ace-
tate (2.0 mL) and PCL (0.250 g) in CH2Cl2 (20 mL) was stirred at
r.t. for 48 h. The reaction mixture was filtered and the residue thor-
oughly washed with Et2O. The combined organic extracts were con-
centrated in vacuo and the residue chromatographed (silica gel,
EtOAc–hexane, 0–10%) to furnish pure (R)-12 and (S)-13.
Anal. Calcd for C25H46O: C, 82.80; H, 12.78. Found: C, 82.63; H,
12.93.
(4Z,8Z)-Pentacosa-4,8-dien-1-ol (9)
To a mixture of P-2 Ni [prepared from Ni(OAc)2·4H2O (0.222 g,
8.83 mmol) and NaBH4 (0.2 g, 5.26 mmol)] and ethylenediamine
(EDA, 0.2 mL) in EtOH (15 mL) was added compound 8 (2.9 g,
8.01 mmol). The mixture was shaken under a slight positive pres-
sure of hydrogen and after the required uptake of H2, the mixture
was passed through a pad of silica gel (2 ) and the pad eluted with
Et2O. The combined eluents were concentrated to furnish pure 9;
yield: 2.62 g (90%).
(S)-13
Yield: 0.423 g (47%); mp 79 °C (Et2O); [ ]D22 –5.95 (c 1.18, Et2O).
IR (film): 3700–3500, 2884, 1740 cm–1.
1H NMR: = 0.9 (dist. t, 3 H), 1.32 (br s, 30 H), 2.07–2.24 (m con-
taining a s at = 2.1, 7 H), 2.32–2.45 (m, 4 H), 4.78 (t, J = 6 Hz, 1
H), 5.2–5.4 (m, 4 H), 8.4 (br s, D2O exchangeable, 1 H).
Synthesis 2004, No. 4, 595–599 © Thieme Stuttgart · New York