Preparation and odour of cis- and trans-2-methyltetrahydrofuran-3-thiol acetates

Article abstract of DOI:10.3184/174751914X13942064030180

The preparation of cis- and trans-2-methyltetrahydrofuran-3-thiol acetates from (E)-3-penten-1-ol is reported. The mesylate of (E)-3-penten-1-ol was converted into trans- or cis-2-methyl-3-hydroxytetrahydrofuran by oxidation with H₂O₂ and HCOOH or with KMnO₄. cis- or trans-2-Methyltetrahydrofuran-3-thiol acetate was prepared by mesylation and an S_N2 nucleophilic substitution with AcSH from trans- or cis-2-methyl-3-hydroxytetrahydrofuran respectively. The configuration of the products was confirmed by their synthesis. Olfactory evaluation of cis- and trans-2-methyltetrahydrofuran-3-thiol acetates indicated some differences both in odour feature and intensity.

Full text of DOI:10.3184/174751914X13942064030180

236 RESEARCH PAPER
VOL. 38 APRIL, 236–239
JOURNAL OF CHEMICAL RESEARCH 2014
Preparation and odour of cis- and trans-2-methyltetrahydrofuran-3-thiol
acetates
Yifeng Dai, Baoguo Sun, Shaoxiang Yang, Yongguo Liu, Hongyu Tian* and Junqiang Shao
School of Food Chemistry, Beijing Key Laboratory of Flavor Chemistry, Beijing Technology and Business University, Beijing 100048, P.R. China
The preparation of cis- and trans-2-methyltetrahydrofuran-3-thiol acetates from (E)-3-penten-1-ol is reported. The mesylate
of (E)-3-penten-1-ol was converted into trans- or cis-2-methyl-3-hydroxytetrahydrofuran by oxidation with H2O2 and HCOOH
or with KMnO4. cis- or trans-2-Methyltetrahydrofuran-3-thiol acetate was prepared by mesylation and an SN2 nucleophilic
substitution with AcSH from trans- or cis-2-methyl-3-hydroxytetrahydrofuran respectively. The configuration of the products
was confirmed by their synthesis. Olfactory evaluation of cis- and trans-2-methyltetrahydrofuran-3-thiol acetates indicated
some differences both in odour feature and intensity.
Keywords: 2‑methyltetrahydrofuran‑3‑thiol acetate, diastereoisomer, preparation, odour
(±)‑2‑Methyltetrahydrofuran‑3‑thiol acetate has a sulfurous,
roasted meat odour and has been approved as a flavour
compound in 2011 with FEMA (Flavour and Extract
Manufacturers’ Association) No. 4686 shown on the FEMA
GRAS(GenerallyRecognizedasSafe)list25.1 Thiswas20 years
later than the parent alcohol, (±)‑2‑methyltetrahydrofuran‑
3‑thiol which was FEMA No. 3787 on the GRAS list 16.2 It
is well known for 2‑methyltetrahydrofuran‑3‑thiol that the
trans-isomer possesses a stronger meaty and roasted note
while the cis-isomer is weaker and has a more sulfurous and
musty note.3 However, the cis/trans-mixture combines both
notes in a full‑body meat flavour. The odour discrepancy
between the trans- and cis-isomers of aroma chemicals occurs
commonly, such as methyl dihydroisojasmonate and methyl
jasmonate, the cis-isomer of which is more desirable.4–7 As far
as we know, the odour properties of trans- and cis-isomers of
2‑methyltetrahydrofuran‑3‑thiol acetate are still unknown.
The diastereoisomers of 2‑methyltetrahydrofuran‑3‑thiol
were prepared by an iodocyclisation approach starting from (Z)‑
and (E)‑3‑pentenols respectively, produced from 3‑pentyn‑1‑ol
reduced by catalytic hydrogenation or LiAlH4.3 The commercial
form of 2‑methyltetrahydrofuran‑3‑thiol is a mixture where the
isomer ratio is about 1/1. This is blended by two products with
different isomer ratios produced from different routes. We have
developed a new approach to producing the trans- and cis-
isomers of 2‑methyltetrahydrofuran‑3‑thiol acetate in order to
explore the odour properties of these isomers (Scheme 1).
Results and discussion
In our route, trans- and cis-isomers of 2‑methyltetrahydrofuran‑
3‑thiol acetate were obtained from the same intermediate,
(E)‑3‑penten‑1‑ol 2, which was prepared by the Knoevenagel
condensation of propanal and malonic acid, followed by
reduction with LiAlH4. The Knoevenagel condensation gave a
10:1 mixture of (E)‑3‑pentenoic acid 1 and by‑product (E)‑2‑
pentenoic acid in about 30% yield. The mixture was used in the
next step without further purification. (E)‑3‑Penten‑1‑ol 2 was
converted into trans-2‑methyl‑3‑hydroxytetrahydrofuran 4 by
epoxidation of its mesylate with H2O2 and HCOOH followed
by ring closure in the presence of NaOH in about 78% overall
yield. The direct epoxidation of 2 without mesylation was also
tried, which gave 4 in a relatively low yield of 59% (Scheme 2).
The
transformation
of
trans-2‑methyl‑3‑hydroxy‑
tetrahydrofuran
4
into cis-2‑methyltetrahydrofuran‑3‑thiol
acetate 6 was attempted by two different routes. In one
route, 4 was reacted with MsCl to give trans-2‑methyl‑
3‑mesyloxytetrahydrofuran 5 in about 89% yield. This
was converted into 6 in about 81% yield through an SN2
nucleophilic substitution by AcSH. The alternative was that 4
underwent the Mitsunobu reaction with DIAD, Ph3P and AcSH
1
to produce 6 directly in about 65% yield (Scheme 3). The H
NMR spectra of the products obtained from these two ways
identical to each other. To confirm the configuration of the
synthesised 2‑methyltetrahydrofuran‑3‑thiol acetate, cis-2‑
methyltetrahydrofuran‑3‑thiol acetate was prepared in about
Malonic acid
LiAlH4
MsCl
H
OH
OMs
OH
O
O
1
2
3
SAc
CH3
OH
CH3
OMs
CH3
H2O2, HCOOH;
NaOH
MsCl
MsCl
AcSH
O
O
4
O
5
6
SAc
CH3
OMs
CH3
OH
CH3
KMnO4
AcSH
O
9
O
O
8
7
Scheme 1 Preparation of trans- and cis-2-methyltetrahydrofuran-3-thiol acetates.
* Correspondent. E‑mail: tianhy@btbu.edu.cn
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JOURNAL OF CHEMICAL RESEARCH 2014 237
OH
CH3
OH
CH3
SAc
CH3
H2O2, HCOOH;
NaOH
OH
DIAD, Ph3P, AcSH
O
4
O
4
O
2
6
MsCl
H2O2, HCOOH;
NaOH
AcSH
I
OMs
I2
OH
3
CH3
O
10
Scheme 2 Preparation of trans-2-methyl-3-hydroxytetrahydrofuran.
2
Scheme 3 Preparation of cis-2-methyltetrahydrofuran-3-thiol acetate by
32% overall yield through an iodocyclisation of 2 followed
by an SN2 nucleophilic substitution with AcSH according
to the literature method (Scheme 3).3 As expected, product 6
obtained by epoxidation of 2 with H2O2 and HCOOH, followed
by mesylation and nucleophilic substitution or by Mitsunobu
reaction, has the same configuration as the iodocyclisation
approach of 2 in the literature.
(E)‑3‑Penten‑1‑yl mesylate 3 was oxidised by KMnO4 to give
cis-2‑methyl‑3‑hydroxytetrahydrofuran 7 in about 83% yield.
An alternative approach was used to prepare 7, in which trans-
2‑methyl‑3‑hydroxytetrahydrofuran 4 was converted into its
cis-isomer 7 by the Mitsunobu reaction with DIAD, Ph3P and
p‑NO2PhCOOH followed by hydrolysis in about 62% overall
yield (Scheme 4). The NMR spectra of the products from the two
differentrouteswereidenticalandshowedsignificantdifferences
from the data of its isomer 4. trans-2‑Methyltetrahydrofuran‑3‑
thiol acetate 9 was obtained from 7 through a mesylation and an
SN2 nucleophilic substitution with AcSH.
Mitsunobu reaction or iodocyclisation.
The
odour
of
trans-
and
cis-isomers
of
2‑methyltetrahydrofuran‑3‑thiol acetate were evaluated. The
cis-isomer presents a meaty aroma with a Chinese broccoli
note; whereas the trans-isomer has a meaty aroma with pickled
potherb mustard note. The cis-isomer has a stronger aroma
than the trans-isomer. It is well known that odour differences
between the two enantiomers also commonly exist. Thus only
(+)‑(1R,2S)‑cis-methyl dihydroisojasmonate is sensorially
active8 after the (±)‑cis-isomer was identified to be the only
intense and characteristic component of the synthetic trans-
and cis-mixture.9 Therefore, the preparation of the four
stereoisomers of 2‑methyltetrahydrofuran‑3‑thiol acetate is
under investigation in our laboratory in order to identify the
odour properties of each stereoisomer.
As far as we know, 2‑methyltetrahydrofuran‑3‑thiol
acetate is the precursor of 2‑methyltetrahydrofuran‑3‑thiol
in the industrial production. The mixture of cis- and trans-2‑
methyltetrahydrofuran‑3‑thiol acetate was obtained starting
from 2,3‑dihydrofuran by electrophilic addition of halogen,
methylation with Grignard reagent and nucleophilic substitution
by AcSH. Generally, bromine gave the trans-isomer as the
major product (70%) whereas chlorine gave the cis-isomer as
the major product (70%) (Scheme 5).
In summary, both trans- and cis-2‑methyltetrahydrofuran‑
3‑thiol acetates have been prepared from (E)‑3‑penten‑1‑
ol, which was easily accessible by the reduction of (E)‑3‑
pentenoic acid obtained from the Knoevenagel condensation
of propanal and malonic acid. The trans- and cis-isomers
present some differences in odour feature and intensity. The
route is suitable for the industrial production of trans- and cis-
2‑methyltetrahydrofuran‑3‑thiol acetates separately.
OH
OH
CH3
OPNB
CH3
DIAD, Ph3P, p-NO2PhCOOH
NaOH
CH3
O
O
O
4
11
7
PNB: p-nitrobenzoyl
Scheme 4 The preparation of cis-2-methyl-3-hydroxytetrahydrofuran from trans-isomer by Mitsunobu reaction.
SAc
X
X
CH3
SAc
CH3
O
X2
AcSH
CH3MgX
6
X
CH3
O
O
O
O
9
Scheme 5 The industrial production of 2-methyltetrahydrofuran-3-thiol acetate.
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238 JOURNAL OF CHEMICAL RESEARCH 2014
From (E)‑3‑penten‑1‑ol 2; compound 2 (1.7 g, 0.02 mol) was added to
a mixture of 30% hydrogen peroxide (10 mL, 0.1 mol) and 88% formic
acid (13 mL, 0.3 mol) during a period of 1 h. The reaction mixture was
cooled and kept at 40–45 °C during the addition. After the addition, the
mixture was stirred for 5 h at 40 °C. The mixture was cooled with an ice
bath and neutralised with cold 35% sodium hydroxide aqueous solution
until pH 9. The mixture was stirred at room temperature for 3 h. The
aqueous layer was extracted with ether and the organic layers were
washed with brine and dried over MgSO4. The solvent was evaporated
under vacuum and the residue was purified by column chromatography
(petroleum ether/ethyl acetate, 6:1) to give 4 as a light yellow oil (1.2 g,
59% yield). The NMR spectra of the product corresponded with those
of the product obtained from 3.
Experimental
Di‑iso‑propylazodicarboxylate (DIAD) and LiAlH4 were purchased
from Beijing Bailingwei Science and Technology Company, and
the others were purchased from Beijing Huaxue Shiji Company. The
NMR spectra were obtained on a Bruker AV300 MHz NMR (Bruker,
Fällanden, Zürich, Switzerland). The high resolution mass spectra
were performed on a Bruker Apex IV FTMS.
(E)‑3-Pentenoic acid (1): Propanal (18 mL, 0.25 mol) was slowly
added at 40 °C over 1 h to a mixture of malonic acid (78 g, 0.75 mol),
piperidine (0.25 mL, 2.5 mmol) and xylene (100 mL). The reaction
apparatus was equipped with a Dean–Stark trap for the continuous
removal of water during the reaction. The reaction temperature
was raised to reflux after the addition. When no more water was
separated, the reaction mixture was cooled to room temperature and
filtered to remove the excess malonic acid. Xylene was removed under
reduced pressure. The residue was distilled under vacuum (0.4 kPa,
60–65 °C) [lit.10 b.p. 66 °C (4 mmHg)] to give (E)‑3‑pentenoic acid
trans-2-Methyl-3-mesyloxytetrahydrofuran (5): trans-2‑Methyl‑
3‑hydroxytetrahydrofuran 4 (3.2 g, 31 mmol) was dissolved in dry
dichloromethane (40 mL) and cooled to 0 °C. Triethylamine (9 mL,
62 mmol) and methanesulfonylchloride (3.0 mL, 40 mmol) were
added in succession at 0–5 °C. The reaction mixture was stirred at
room temperature overnight. The reaction mixture was treated with
10% HCl solution (30 mL) at 0–5 °C. The reaction mixture was then
extracted three times with dichloromethane, and the combined organic
layers were washed with saturated aqueous NaHCO3 solution and brine
successively and dried over MgSO4. After concentration under reduced
pressure, the residue was distilled under vacuum (0.3 kPa, 80–85 °C)
1
1 as a colourless oil (7.5 g, 30% yield). H NMR (CDCl3) δ 1.68 (3H,
d, J=6.0 Hz, Me(5)), 3.05 (2H, d, J=5.7 Hz, H–C(2)), 5.54 (2H, m,
H–C(3) and C(4)), 10–12 (1H, br, –COOH). 13C NMR (CDCl3) δ 17.9
(Me), 37.8(C(2)), 121.9 (C(4)), 130.0 (C(3)), 179.0 (C(1)). 1H NMR data
were identical to those reported in the literature.10
(E)-3-Penten-1-ol (2): Lithium aluminium hydride (3.8 g, 0.1 mol)
was suspended in dry tetrahydrofuran (50 mL) under nitrogen. (E)‑
3‑Pentenoic acid 1 (10 g, 0.1 mol) dissolved in dry tetrahydrofuran
(30 mL) was added dropwise at 0–5 °C. After the addition, the
reaction mixture was heated at reflux for 2 h. Then it was cooled to
0 °C and quenched by careful addition of distilled water (15 mL) and
10% sodium hydroxide solution (10 mL). The mixture was filtered
over Na2SO4, and the filtrate was evaporated under reduced pressure
(0.4 kPa, 35–40 °C) [lit.11 b.p. 130–138 °C] to give (E)‑3‑pentenol 2 as a
yellow oil (7.6 g, 88% yield). 1H NMR (CDCl3) δ 1.65 (3H, d, J=6.3 Hz,
Me(5)), 2.22 (2H, m, H–C(2)), 3.59 (2H, t, J=6.3 Hz, H–C(1)), 5.38
(1H, m, H–C(4)), 5.57 (1H, m, H–C(3)). 13C NMR (CDCl3) δ18.0 (Me),
1
to give 5 as a light yellow oil (5.0 g, 89% yield). H NMR (CDCl3) δ
1.26 (3H, d, J=6.6 Hz, Me–C(2)), 2.18 (1H, m, H–C(3)), 2.24 (1H, m,
H–C(3)), 3.04 (3H, s, Me(mesyl)), 3.89 (1H, td, J=9.3, 6.6 Hz, H–C(5)),
4.01 (1H, td, J=8.4, 3.3 Hz, H–C(5)), 4.12 (1H, m, H–C(2)), 4.82 (1H,
m, H–C(3)). 13C NMR δ 18.5 (Me–C(2)), 32.5 (C(4)), 38.4 (Me(mesyl)),
66.3 (C(5)), 79.7 (C(2)), 85.1 (C(3)). HRESIMS, m/z 203.03502
[M+Na+] (calcd for C6H12NaO4S, 203.03485).
cis-2-Methyltetrahydrofuran-3-thiol acetate (6): From trans-
2‑methyl‑3‑mesyloxytetrahydrofuran (5); thioacetic acid (0.9 g,
12 mmol) was added to a mixture of anhydrous potassium carbonate
(2.2 g, 16 mmol), absolute acetonitrile (50 mL) and 18‑crown‑6 (0.1 g,
0.4 mmol). The mixture was stirred at room temperature for 20 min
and trans-2‑methyl‑3‑mesyloxytetrahydrofuran 5 (1.4 g, 8 mmol) was
added dropwise. After the addition, the mixture was heated at reflux
for 24 h. The reaction mixture was cooled to room temperature and
filtered. The filtrate was acidified with 5% aqueous HCl, and then
extracted with diethyl ether. The combined organic layers were washed
with saturated aqueous NaHCO3 solution and brine in succession and
dried over MgSO4. After concentration under vacuum, the residue
was submitted to column chromatography (petroleum ether/ethyl
acetate, 10:1) to give 6 as a light yellow oil (1.04 g, 81% yield). 1H NMR
(CDCl3) δ 1.19 (3H, d, J=6.3 Hz, Me), 1.93 (1H, m, H–C(4)), 2.48 (1H,
m, H–C(4)), 2.34 (3H, s, Me(Ac)), 3.75 (1H, td, J=8.4, 6.3 Hz, H–C(5)),
3.90 (1H, td, J=8.4, 6.3 Hz, H–C(5)), 4.13 (1H, m, H–C(2)), 4.05 (1H,
m, H–C(3)). 13C NMR (CDCl3) δ 16.8 (Me), 30.6 (Me(Ac)), 33.5 (C(4)),
46.3 (C(3)), 65.9 (C(5)), 76.5 (C(2)), 195.4 (C=O). HRESIMS, m/z
161.06313 [M+H+] (calcd for C7H13O2S, 161.06308).
From trans-2‑methyl‑3‑hydroxytetrahydrofuran 4 by the Mitsunobu
reaction;13 a solution of trans-2‑methyl‑3‑hydroxytetrahydrofuran 4
(1.6 g, 15.6 mmol) in tetrahydrofuran (40 mL) was treated with Ph3P
(8.4 g, 32 mmol), DIAD (6.5 g, 32 mmol) and thioacetic acid (2.43 g,
32 mmol). After the addition, the mixture was stirred for 1 day at
room temperature. The solvent was removed under reduced pressure.
The residue was purified twice by flash column chromatography
(petroleum ether/ethyl acetate, 10:1) to give 6 as a yellow oil (1.6 g,
65% yield). The NMR spectra of the product were identical with those
of the product obtained from 5.
1
35.9 (C(2)), 62.0 (C(1)), 127.2 (C(4)), 128.1 (C(3)). The H NMR data
were identical with those reported in the literature.11
(E)-3-penten-1-yl mesylate (3): (E)‑3‑pentenol 2 (5 g, 58 mmol) was
dissolved in dry CH2Cl2 (40 mL) and cooled to 0 °C. Triethylamine
(16.2 mL, 116 mmol) and methanesulfonylchloride (5.8 mL,
75.4 mmol) were slowly added at 0–5 °C successively. After stirring
at room temperature for 12 h, the reaction mixture was acidified by
addition of 5% solution of HCl (30 mL) at 0–5 °C. The reaction mixture
was then extracted three times with CH2Cl2, and the combined organic
phases were washed once with saturated aqueous NaHCO3 solution
and once with saturated brine, dried over MgSO4, and concentrated in
vacuo. The residue was distilled under vacuum (0.4 kPa, 100–105 °C)
to give 3 as a yellow oil (8.7 g, 92% yield). 1H NMR (CDCl3) δ 1.64 (3H,
d, J=6.3 Hz, Me(C(5))), 2.39 (2H, q, J=6.9 Hz, H–C(2)), 2.96 (3H, s,
Me(mesyl)), 4.17 (2H, t, J=6.9 Hz, H–C(1)), 5.36 (1H, m, H–C(4)), 5.57
(1H, m, H–C(3)). 13C NMR (CDCl3) δ 17.5 (Me(C(5)), 31.9 (C(2)), 36.8
(Me(mesyl)), 69.4 (C(1)), 124.5 (C(4)), 128.7 (C(3)). The 1H NMR data
corresponded with those reported in the literature.11
trans-2-Methyl-3-hydroxytetrahydrofuran (4): From (E)‑3‑penten‑
1‑yl mesylate; compound 3 (7.5 g, 0.046 mol) was added to a mixture
of 30% hydrogen peroxide (23 mL, 0.23 mol) and 88% formic acid
(31 mL, 0.7 mol) over 1 h. The reaction mixture was kept at 40–45 °C
during the addition. Then the mixture was stirred for 5 h at 40 °C.
The mixture was cooled with ice bath and neutralised with cold 35%
aqueous NaOH solution until pH 9 and then kept stirring for 3 h.
The aqueous layer was extracted with ether and the organic layers
were washed with brine, dried over MgSO4, and concentrated under
vacuum. The residue was distilled under reduced pressure (0.1 kPa,
From (E)‑3‑penten‑1‑ol 2 by iodocyclisation; 2 (2.6 g, 0.03 mol) was
added to a mixture of iodine (11.4 g, 0.045 mol) and methanol (40 mL)
dropwise. The mixture was stirred at room temperature for 2 h. Then
NaHCO3 (5 g, 0.06 mol) was added in batches and the reaction mixture
was stirred for 5 h at room temperature. Saturated aqueous sodium
thiosulfate solution was added dropwise until the reddish‑brown
colour disappeared. The reaction mixture was filtered, and the filtrate
1
36–38 °C) to give 4 as a light yellow oil (4.0 g, 85% yield). H NMR
(CDCl3) δ 1.16 (3H, d, J=6.3 Hz, Me), 1.84 (1H, m, H–C(4)), 2.16 (1H,
m, H–C(4)), 2.23 (1H, br, –OH), 3.82 (1H, m, H–C(3)), 3.87–4.01 (3H,
m, H–C(2) and C(5)). 13C NMR (CDCl3) δ 18.8 (Me), 34.3 (C(4)), 66.0
(C(5)), 76.7 (C(3)), 81.7 (C(2)). The NMR data corresponded with those
reported in the literature.12
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JOURNAL OF CHEMICAL RESEARCH 2014 239
was extracted four times with CH2Cl2. The combined organic phases
were washed once with brine, dried over MgSO4, and concentrated in
vacuo to give the crude product trans-2‑methyl‑3‑iodotetrahydrofuran
combined organic phases were washed once with brine, dried over
MgSO4, and concentrated in vacuo. The crude product was purified by
column chromatography (petroleum ether/ethyl acetate, 6:1) to give 7
as a light yellow oil (2.2 g, 90% yield). The NMR data were consistent
with those of the product obtained above.
cis-2-Methyl-3-mesyloxytetrahydrofuran (8): cis-2‑Methyl‑3‑
hydroxytetrahydrofuran 7 was converted to its mesylate 8 by the same
procedure as shown for 5. 90% yield. 1H NMR (CDCl3) δ 1.33 (3H, d,
J=6.6 Hz, Me–C(2)), 2.34 (2H, m, H–C(4)), 3.05 (3H, s, Me(mesyl)),
3.80 (1H, td, J=8.4, 5.4 Hz, H–C(5)), 4.08 (1H, q, J=8.1 Hz, H–C(5)),
3.95 (1H, qd, J=6.3, 3.6 Hz, H–C(2)), 5.13 (1H, ddd, J=5.4, 3.6, 2.1 Hz,
H–C(3)). 13C NMR δ 14.4 (Me–C(2)), 34.0 (C(4)), 38.5 (Me(mesyl)),
65.8 (C(5)), 77.2 (C(2)), 81.9 (C(3)). HRESIMS, m/z 181.05317 [M+H+]
(calcd for C6H13O4S, 181.05291).
1
10 as a brown oil (2.5 g, 40% yield). H NMR (CDCl3) δ 1.29 (3H, d,
J=6.0 Hz, Me), 2.28 (1H, m, H–C(4)), 2.56 (1H, m, H–C(4)), 3.65 (1H,
m, H–C(3)), 3.88 (2H, m, H–C(5)), 4.07 (1H, m, H–C(2)). 13C NMR
(CDCl3) δ 17.6 (Me), 24.9 (C(3)), 38.2 (C(4)), 66.8 (C(5)), 84.0 (C(2)).
HRESIMS, m/z 212.97770 [M+H+] (calcd for C5H10IO, 212.97708).
Thioacetic acid (1.1 g, 15 mmol) was added to a mixture of anhydrous
potassium carbonate (2.8 g, 20 mmol), absolute acetonitrile (60 mL)
and 18‑crown‑6 (0.13 g, 0.5 mmol). The mixture was stirred at room
temperature for 20 min and 10 (2.1 g, 10 mmol) was added. After the
addition, the mixture was heated at reflux overnight. The reaction
mixture was cooled to room temperature and filtered. The filtrate was
acidified by addition of 5% aqueous HCl, and extracted four times with
diethyl ether. The combined organic phases were washed once with
saturated aqueous NaHCO3 solution and once with saturated brine,
dried over magnesium sulfate, and concentrated in vacuo. The crude
product was purified by column chromatography (petroleum ether/
ethyl acetate, 10:1) to give 6 as a light yellow oil (0.32 g, 80% yield).
The NMR spectra of the product were identical with those of the
product obtained above.
cis-2-Methyl-3-hydroxytetrahydrofuran (7): From (E)‑3‑penten‑
1‑yl mesylate 3;14 a solution of KMnO4 (4 g, 25 mmol) in acetone/water
(70 mL, 2.5:1) was added at 0 °C over 20 min to a solution of 3 (3.3 g,
20 mmol) in acetone (50 mL). The temperature of the reaction mixture
were kept at 0 °C stirring for 3 h. A solution of NaHSO3 (45 mL, 40%
in water) was added. The mixture was filtered through a pad of Celite
and the acetone was removed in vacuo. The residue was saturated
by addition of NaCl and extracted with CH2Cl2. After drying and
evaporation of solvents in vacuo the remaining crude was purified by
column chromatography (petroleum ether/ethyl acetate, 6:1) to give 7
as a light yellow oil (1.7 g, 83% yield). 1H NMR (CDCl3) δ 1.27 (3H, d,
J=6.3 Hz, Me), 1.93 (1H, m, H–C(4)), 2.22 (1H, m, H–C(4)), 3.73 (2H,
m, H–C(3) and C(5)), 4.03 (1H, dd, J=15.9, 8.1 Hz, H–C(5)), 4.17 (1H,
m, H–C(2)). 13C NMR (CDCl3) δ 13.7 (Me), 35.4 (C(4)), 65.5 (C(5)), 72.8
(C(3)), 78.6 (C(2)). The NMR data were matched with those reported in
the literatiure.12.
trans-2-methyltetrahydrofuran-3-thiol acetate (9): cis-2‑Methyl‑
3‑mesyloxytetrahydrofuran 8 reacted with AcSH to give 9 according
1
to the procedure similar to that for 6. 85% yield. H NMR (CDCl3) δ
1.28 (3H, d, J=6.0 Hz, Me–C(2)), 1.85 (1H, m, H–C(4)), 2.49 (1H, m,
H–C(4)), 2.34 (3H, s, Me(Ac)), 3.52 (1H, td, J=8.7, 7.2 Hz, H–C(5)),
3.96 (1H, td, J=8.7, 5.7 Hz, H–C(5)), 3.71–3.88 (2H, m, H–C(2) and
C(3)). 13C NMR δ 19.2 (Me), 30.6 (Me(Ac)), 33.2 (C(4)), 46.6 (C(3)), 66.7
(C(5)), 79.9 (C(2)), 195.3 (C=O). HRESIMS, m/z 161.06319 [M+H+]
(calcd for C7H13O2S, 161.06308).
Financial support from the National Natural Science Foundation
of China (No. 31271932), the National Key Technology
R&D Program (2011BAD23B01) and the Importation and
Development of High‑Caliber Talents Project of Beijing
Municipal Institutions (CIT&TCD20140306) is gratefully
acknowledged.
Received 7 January 2014; accepted 14 February 2014
Paper 1402384 doi: 10.3184/174751914X13942064030180
Published online: 2 April 2014
References
From trans-2‑methyl‑3‑hydroxy‑tetrahydrofuran 4 by Mitsunobu
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1
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7
1
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8
9
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m, H–C(4)), 3.83 (1H, m, H–C(5)), 4.04 (1H, m, H–C(5)), 4.12 (1H, m,
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mixture was stirred at room temperature for 5 h. The reaction mixture
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