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J. Klimentova et al. / Bioorg. Med. Chem. 14 (2006) 7681–7687
7685
mide. The solution of alkyl bromide (0.250 mol) in
anhydrous THF (50 mL) was slowly added to magne-
sium (0.252 mol) in anhydrous THF (250 mL). The reac-
tion was initiated by adding a crystal of iodine. The
mixture was then heated to reflux until all the magne-
sium dissolved.
OH), 1.61–1.03 (17H, m, CH, 8CH2), 0.84 (6H, d,
J = 6.6, 2CH3). 13C NMR (75 MHz, CDCl3): 63.0,
39.0, 32.7, 29.9, 29.6, 29.4, 27.9, 27.4, 25.7, 22.6.
4.1.4.5. Compound 5e (11-methyldodecanol). C13H28O,
200.37 gmolÀ1, yield 68%, colourless oil, bp 146–147 °C/
10 torr (bp 139 °C/11 torr was reported32). FT-IR (neat):
mmax 3332, 2953, 2925, 2854, 1467, 1384, 1366, 1057,
The salt 2a or 2b (0.160 mol) was suspended in anhy-
drous THF (250 mL), cooled to À10 °C and the solution
of the catalyst Li2CuCl4 (0.001 mol) in THF was added.
Then the prepared solution of Grignard reagent 3a–3d
or 4a–4b was added dropwise under vigorous stirring
at the temperature not exceeding À5 °C. The colour of
the mixture changed from orange through green and
blue to white. After adding all the Grignard reagent
the temperature was kept at À10 °C for another 4 h.
After warming to room temperature LiAlH4
(0.160 mol) was added and the mixture was heated to re-
flux for 1 h. Then the mixture was poured on crushed ice
and the resulting white precipitate was dissolved by add-
ing 30% H2SO4. The organic layer was separated and
the water phase was extracted three times with diethyl
ether. The organic layers were combined, dried over
anhydrous Na2SO4 and evaporated in vacuum. The
resulting light brown oil was purified by fraction vacu-
um distillation.
721 cmÀ1 1H NMR (300 MHz, CDCl3): 3.62 (2H, t,
.
J = 6.6, CH2OH), 1.67 (1H, br s, OH), 1.61–1.03 (19H,
m, CH, 9CH2), 0.85 (6H, d, J = 6.6, 2CH3). 13C NMR
(75 MHz, CDCl3): 63.0, 39.0, 32.8, 29.9, 29.7, 29.61,
29.59, 29.4, 27.9, 27.4, 25.7, 22.5.
4.1.4.6. Compound 6a (8-ethyldecanol). C12H26O,
186.34 gmolÀ1, yield 66%, colourless oil, bp 131–
132 °C/10 torr. FT-IR (neat): mmax 3355, 2960, 2926,
2857, 1457, 1379, 1056, 721 cmÀ1
.
1H NMR
(300 MHz, CDCl3): 3.62 (2H, t, J = 6.6, CH2OH),
1.62–1.49 (1H, m, CH), 1.46 (1H, br s, OH), 1.38–1.06
(16H, m, 8CH2), 0.82 (6H, t, J = 7.4, 2CH3). 13C
NMR (75 MHz, CDCl3): 63.0, 40.3, 32.8, 30.1, 29.5,
26.7, 25.7, 25.4, 10.9.
4.1.4.7. Compound 6b (10-ethyldodecanol). C14H30O,
214.39 gmolÀ1, yield 64%, colourless oil, bp 159–
160 °C/10 torr (bp 155–160 °C/10 torr was reported34).
FT-IR (neat): mmax 3321, 2960, 2923, 2853, 1461, 1379,
4.1.4.1. Compound 5a (7-methyloctanol). C9H20O,
144.26 gmolÀ1, yield 62%, colourless oil, bp 96–97 °C/
10 torr (bp 100 °C/13 torr was reported30). FT-IR (neat):
mmax 3332, 2954, 2927, 2868, 2856, 1467, 1384, 1366,
1056, 721 cmÀ1 1H NMR (300 MHz, CDCl3): 3.67–
.
3.55 (2H, m, CH2OH), 2.01 (1H, br s, OH), 1.81–
1.72 (1H, m, CH), 1.39–1.04 (20H, m, 10CH2), 0.81
(6H, t, J = 7.4, 2CH3). 13C NMR (75 MHz, CDCl3):
62.9, 40.3, 32.74, 32.69, 30.1, 29.6, 29.4, 26.7, 25.7,
25.4, 10.9.
1058, 724 cmÀ1 1H NMR (300 MHz, CDCl3): 3.61
.
(2H, t, J = 6.6, CH2OH), 2.14 (1H, s, OH), 1.62–1.02
(11H, m, CH, 5CH2), 0.84 (6H, d, J = 6.6, 2CH3). 13C
NMR (75 MHz, CDCl3): 73.0, 38.9, 32.7, 29.6, 27.9,
27.3, 25.7, 22.6.
4.1.5. Preparation of the acids 7a–7e and 8a–8b. CrO3
(0.056 mol) was dissolved in 90% w/w acetic acid
(56 mL) and the solution was cooled to +5 °C. The
alcohol 5a–5e or 6a and 6b (0.014 mol) was added
dropwise under vigorous stirring at the temperature
not exceeding +5 °C. The temperature was kept for
next 2 h and then the mixture was allowed to stand
at room temperature overnight. Then it was diluted
with water, extracted five times with diethyl ether
and the organic extracts were washed by saturated
solution of Na2CO3. The water layer was then acidi-
fied by HCl, washed five times by diethyl ether and
the combined organic layers were washed with water,
dried over anhydrous Na2SO4 and evaporated in
vacuum. The resulting yellow oil was purified by col-
umn chromatography on silica gel using hexane/ethyl
acetate 9:1 as an eluent.
4.1.4.2. Compound 5b (8-methylnonanol). C10H22O,
158.29 gmolÀ1, yield 62%, colourless oil, bp 103–
104 °C/10 torr (bp 80 °C/6 torr was reported31). FT-IR
(neat): mmax 3331, 2953, 2927, 2866, 2854, 1467, 1384,
1366, 1058, 723 cmÀ1 1H NMR (300 MHz, CDCl3):
.
3.61 (2H, t, J = 6.6, CH2OH), 1.94 (1H, s, OH), 1.60–
1.02 (13H, m, CH, 6CH2), 0.84 (6H, d, J = 6.6, 2CH3).
13C NMR (75 MHz, CDCl3): 63.0, 39.0, 32.7, 29.8,
29.4, 27.9, 27.3, 25.7, 22.6.
4.1.4.3. Compound 5c (9-methyldecanol). C11H24O,
172.31 gmolÀ1, yield 63%, colourless oil, bp 119–
120 °C/10 torr (bp 135–136 °C/12 torr was reported32).
FT-IR (neat): mmax 3328, 2953, 2926, 2854, 1467, 1384,
1366, 1056, 722 cmÀ1 1H NMR (300 MHz, CDCl3):
.
3.60 (2H, t, J = 6.7, CH2OH), 1.93 (1H, s, OH), 1.60–
1.02 (15H, m, CH, 7CH2), 0.84 (6H, d, J = 7.2, 2CH3).
13C NMR (75 MHz, CDCl3): 62.9, 39.0, 32.7, 29.8,
29.6, 29.4, 27.9, 27.4, 25.7, 22.6.
4.1.5.1. Compound 7a (7-methyloctanoic acid).
C9H18O2, 158.24 gmolÀ1, yield 72%, pale yellow oil,
mp 3–5 °C (mp 0 °C was reported35). FT-IR (CHCl3):
mmax 3515, 3028, 2956, 2931, 2869, 1708, 1467, 1412,
1
4.1.4.4.
Compound
5d
(10-methylundecanol).
1385, 1366, 1280 cmÀ1. H NMR (300 MHz, CDCl3):
C12H26O, 186.34 gmolÀ1, yield 74%, colourless oil, bp
135–136 °C/10 torr (bp 147–149 °C/18 torr was report-
ed33). FT-IR (neat): mmax 3335, 2953, 2925, 2854, 1467,
10.96 (1H, br s, COOH), 2.34 (2H, t, J = 7.4,
CH2COOH), 1.69–1.57 (2H, m, CH2CH2COOH),
1.57–1.10 (7H, m, CH, 3CH2), 0.86 (6H, d, J = 6.6,
2CH3). 13C NMR (75 MHz, CDCl3): 180.5, 38.7, 34.1,
29.3, 27.9, 27.0, 25.7, 22.59, 22.55.
1384, 1366, 1057, 721 cmÀ1
.
1H NMR (300 MHz,
CDCl3): 3.62 (2H, t, J = 6.6, CH2OH), 1.94 (1H, s,