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F. Boratyn´ski et al. / Journal of Molecular Catalysis B: Enzymatic 65 (2010) 30–36
2.4.3. ( )-4,6,6-Trimethyl-1-oxepan-2-one (4c)
Yield 90% (the mixture of 4c and 4d), n2D0 = 1.4247, Lit. [19]:
n2D0 = 1.4565 (the mixture of 4c and 4d).
2.6. Enzymatic oxidation of racemic diols 1a–i catalyzed by
HLADH
The reactions were carried out in a buffer at pH 9.0 using FMN
as the effective agent in recycling process of the catalytic amounts
of NAD+ coenzyme used. In the screening experiments diols 1a–i
(0.02 g) and coenzymes: NAD+ (0.007 g) and FMN (0.2 g) were dis-
solved in 0.1 M glycine-NaOH buffer (20 cm3) at 20–25 ◦C. The pH of
the mixture was readjusted to 9 with 2 M NaOH. HLADH (0.002 g)
was added, and the mixture was stirred for appropriate time at
room temperature, with periodic adjustment of the pH to 9. The
mixture turned from its initial clear orange to almost black color
as the reaction proceeded. Samples of the reaction mixtures were
taken after several time intervals (2, 24, 48 and 120 h) and analyzed
by GC.
2.4.4. ( )-4,4,6-Trimethyl-1-oxepan-2-one (4d)
mp = 30–31 ◦C.
2.4.5. ( )-7-Methyl-1-oxepan-2-one (4e)
Yield 70%, n2D0 = 1.4561, Lit. [20]: n2D0 = 1.4564.
2.4.6. ( )-7-Isopropyl-4-methyl-1-oxepan-2-one (4f)
Yield 72%, n2D0 = 1.4521, Lit. [21]: n2D2 = 1.4596.
2.4.7. ( )-3,7,7-Trimethyl-1-oxepan-2-one (4g)
Yield 81%, mp = 45–47 ◦C.
The preparative-scale transformations were performed in the
same conditions in five 20 cm3 vials using 0.1 g of diols 1a–i
(5 × 0.02 g), 0.035 g of NAD+ (5 × 0.007 g), 1 g FMN (5 × 0.2 g)
and HLADH (5 × 0.002 g). When the reaction was completed the
aqueous mixtures were pooled, acidified, washed with NaCl and
extracted with CHCl3. The extracts were dried with anhydrous
MgSO4 and evaporated in vacuo. The crude products were puri-
fied by column chromatography (silica gel, eluent: hexane/acetone,
8:1). The yields and optical rotations of products obtained are given
below. The spectral data for new compounds are also presented.
2.4.8. ( )-4,4,6-Trimethyl-tetrahydropyran-2-one (4i)
Yield 82%, n2D0 = 1.4411, Lit. [22]: n2D0 = 1.4474.
2.5. Reduction of lactones 4a–i
A solution of lactone 4a–i (20 mmol) in diethyl ether (25 cm3)
was added dropwise to LiAlH4 (25 mmol) in diethyl ether (25 cm3).
The mixture was stirred for 1–2 days at room temperature. When
the reaction was completed (GC, TLC), water was added to decom-
pose the excess of LiAlH4. The mixture was then acidified with
0.01 M HCl and the product was extracted with diethyl ether. Then
the extract was washed with saturated NaCl and dried (MgSO4).
The crude product was purified by column chromatography (silica
gel, hexane/acetone, 5:1). The yields and physical data of 1,5-diol
1i and 1,6-diols 1a–g obtained are given below. The spectral data
for compounds 1g,i, not described in literature, are also presented.
2.6.1. Preparative oxidation of ( )-1a
Oxidation of ( )-1a (0.1 g), after 48 h, gave a mixture of: unre-
acted ( )-diol 1a (48%) and ( )-lactone 4a (27%). The column
chromatography of this mixture afforded 0.046 g (46% yield) of
(
)-diol 1a and 0.023 g (23% yield) of ( )-lactone 4a.
2.6.2. Preparative oxidation of ( )-1b
Oxidation of ( )-1b (0.1 g) gave complex mixture of products,
which was not separable.
2.5.1. ( )-2-Methylhexane-1,6-diol (1a)
Yield 62%, n2D0 = 1.4512, Lit. [23]: n2D0 = 1.4556.
2.5.2. ( )-3-Methylhexane-1,6-diol (1b)
2.6.3. Preparative oxidation of ( )-1c
Yield 40%, n2D0 = 1.4547, Lit. [23]: n2D0 = 1.4554.
Oxidation of ( )-1c (0.1 g), after 48 h, gave a mixture of: unre-
acted ( )-diol 1c (53%), ( )-lactone 4c (23%) and hemiacetal 3c
(24%). The column chromatography of this mixture afforded 0.044 g
(44% yield) of ( )-diol 1c and 0.02 g (20% yield) of ( )-lactone 4c.
The oxidation of ( )-1c for longer time (120 h) let to obtain ( )-
lactone 4c as the only product in high (92%) yield.
2.5.3. ( )-2,2,4-Trimethylhexane-1,6-diol (1c)
Yield 85%, n2D0 = 1.4611, Lit. [24]: n2D0 = 1.4626.
2.5.4. ( )-2,4,4-Trimethylhexane-1,6-diol (1d)
Yield 88%, n2D0 = 1.4620, Lit. [24]: n2D0 = 1.4628.
2.6.4. Preparative oxidation of ( )-1d
2.5.5. ( )-Heptane-1,6-diol (1e)
Yield 74%, n2D0 = 1.4522, Lit. [25]: n2D0 = 1.4530.
Oxidation of ( )-1d (0.1 g), after 120 h, gave a mixture of:
(
)-lactone 4d (54%) and hemiacetal 3d (21%). The column
chromatography of this mixture afforded 0.043 g (43% yield) of
)-lactone 4d.
2.5.6. ( )-3,7-Dimethyloctane-1,6-diol (1f)
Yield 95%, n2D0 = 1.4594, Lit. [26]: n2D0 = 1.4615.
(
2.5.7. ( )-2,6-Dimethylheptane-1,6-diol (1g)
2.6.5. Preparative oxidation of ( )-1e
Yield 90%, n2D0 = 1.4541; 1H NMR (␦): 0.89 (d, J = 6.9 Hz, 3H, CH3-
CH<), 1.20 (s, 6H, (CH3)2C<), 1.25–1.70 (m, 7H, CH2-3, CH2-4, CH2-5,
H-2), 1.78 (s, 2H, two OH), 3.40 (dd, J = 10.5, 6.6 Hz, 1H, one of CH2-
1), 3.47 (dd, J = 10.5, 6.0 Hz, 1H, one of CH2-1); IR (film, cm−1): 3350
(s), 2967 (s), 1378 (s), 1040 (s).
Oxidation of ( )-1e (0.1 g), after 48 h, gave mixture of the fol-
lowing products: unreacted diol 1e (9%), (+)-lactone 4e (32%),
hydroxyaldehyde 2e (42%) and hydroxyketone 5e (17%). The col-
umn chromatography of this mixture afforded 0.005 g (5% yield)
of diol 1e, 0.022 g (22% yield) of (+)-(R)-lactone 4e, e.e. > 99%,
[˛]2D5 = +14.1◦ (c 1.5, CHCl3), Lit. [27]: [˛]20 = +16.2◦ (c 1.5, CHCl3),
D
2.5.8. ( )-3,3-Dimethylhexane-1,5-diol (1i)
0.036 g (36% yield) of hydroxyaldehyde 2e and 0.015 g (15% yield)
of hydroxyketone 5e.
Yield 76%, n2D0 = 1.4520; 1H NMR (␦): 0.94 and 0.97 (two s, 6H,
(CH3)2C<), 1.19 (d, J = 6.2 Hz, 3H, CH3-CH<), 1.27 (dd, J = 14.8, 1.7 Hz,
1H, one of CH2-4), 1.44 (dt, J = 14.3, 5.8 Hz, 1H, one of CH2-2), 1.66
(dd, J = 14.8, 8.7 Hz, 1H, one of CH2-4), 1.83 (ddd, J = 14.3, 7.9, 6.5 Hz,
1H, one of CH2-2), 3.32 (s, 2H, two OH), 3.67–3.76 (two m, 2H, CH2-
1), 3.99 (m, 1H, H-5); IR (film, cm−1): 3338 (s), 2960 (s), 1470 (s),
1367 (s), 1050 (s), 1023 (s).
6-Hydroxyheptan-1-al (2e): 1H NMR (␦): 1.19 (d, J = 6.1 Hz, 3H,
–CH3), 1.25–1.70 (m, 6H, CH2-3, CH2-4, CH2-5), 2.46 (t, J = 7.3 Hz,
2H, CH2-2), 3.84 (m, 1H, H-6), 9.77 (m, 1H, –CHO); IR (film, cm−1):
3420 (s), 2927 (s), 1373 (s), 1112 (s).
1-Hydroxyheptan-6-one (5e): 1H NMR (␦): 1.30–1.60 (m, 6H,
CH2-2, CH2-3, CH2-4), 2.10 (s, 3H, CH3-), 2.41 (t, J = 7.2 Hz, 2H, CH2-