Electronic supplementary material
Synthesis of the esters 7-methyloctyl 5-methylhexanoate, 7-methyloctyl octanoate, 7-methyloctyl
7-methyloctanoate, and 7-methyloctyl (Z)-4-decenoate:
General procedure: The esters were synthesized using a modified method of that described by
Tolasch et al. (2007). Commercially available chemicals were used without further purification.
5-Methylhexanoic acid, 5-methylhexyl bromide and (Z)-4-decen-1-ol were purchased from Alfa
Aesar. Tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), dichloromethane (CH2Cl2) and
pyridine was dried and/or distilled prior to use. Preparative liquid chromatography was
performed on normal-phase silica gel (Merck 60, 230-400 mesh, 0.040-0.063 mm, 10-50 g/g of
product mixture) employing a gradient technique with an increasing concentration (0-100%) of
distilled diethyl ether in distilled pentane. Thin-layer chromatography (TLC) was performed to
monitor the progress of the reactions on silica gel plates (Merck 60, pre-coated aluminium foil),
using ethyl acetate (40%) in cyclohexane as an eluent, and plates were visualised by means of
ultraviolet irradiation and/or by spraying with vanillin in sulfuric acid and heating at 120°C.
Purity of the product was checked with GC analysis on a Varian 3300 GC instrument (Varian,
Palo Alto, CA, USA) using an EC-1 column (30 m x 0.32 mm ID, 0.25 μm film thickness
(Alltech, Deerfield, IL, USA)). Nitrogen was used as carrier gas. The column temperature was
maintained at 50°C for 5 min and then increased by 10°C/min to 300°C. Mass spectral analyses
were carried out on a Saturn 2000 GC/MS/MS instrument (Varian), coupled to a Varian 3800
GC instrument (Varian), using a CP-Sil 5 CB column (30 m x 0.32 mm ID, 0.25 μm film
thickness (Varian)). Helium was used as carrier gas at a flow rate of 1 ml/min. The same
temperature program was used as above. NMR spectra were recorded on a Bruker Avance 500
(500 MHz 1H, 125.8 MHz 13C) spectrometer (Bruker, Solna, Sweden) using CDCl3 as solvent
and TMS as internal standard.
7-Methyloctan-1-ol
NaH (2.7 g, 111 mmol) was added in portions to a solution of dimethyl malonate (14.7 g, 111
mmol) and THF (250 mL) at 0°C. The mixture was stirred for 10 min before drop-wise adding 5methylhexyl bromide (2.92 g, 16.3 mmol) in THF (50 mL). The reaction was set on reflux
overnight, and then quenched with NH4Cl (110 mL) and extracted with EtOAc (3 x 50 mL). The
combined organic layers were dried (MgSO4) and evaporated. Most of the excess of dimethyl
malonate was removed by distillation under reduced pressure, using a vigreux column. The crude
malonic ester was then purified by flash chromatography and checked by NMR. The crude
malonic ester (3.3 g, 14.3 mmol) in DMSO (6 mL) was added to a mixture of NaCl (0.84 g) and
H2O (1.0 mL) in DMSO (12 mL) and refluxed over night. The reaction was quenched with H2O
and extracted with EtOAc (2 x 25 mL). The combined organic layers were dried (MgSO4),
concentrated and after flash chromatography a pale yellow oil (2.0 g, 11.6 mmol) was obtained.
The obtained methyl ester was checked by NMR and used in the next step without further
purification. The product ester (1.7 g, 9.9 mmol) in THF (40 mL) was added drop-wise to a
stirred mixture of THF (40 mL) and LiAlH4 (0.76 g, 9.9 mmol) at 0°C. The reaction was allowed
to reach room temperature overnight. The reaction was quenched with NH4Cl and HCl (2 M) at
0°C and extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with
brine (20 mL), dried (MgSO4) and the solvent evaporated. The pale oil was purified by bulb-tobulb distillation (130°C, 2 mbar) to yield the pure (GC) product alcohol (1.29 g, 8.96 mmol) as a
colourless oil in 55% from the bromide. The analytical data were accordingly to those reported in
the literature (Tolasch et al. 2007).
(Z)-4-decenoic acid
(Z)-4-decen-1-ol (3 g, 19.2 mmol) in acetone (160 mL) was stirred on an ice bath and Jones
reagent (28.8 mmol) was added at a temperature below 5°C. After 1 h the reaction was quenched
by adding water (8 mL). The reaction was extracted with Et2O (3 x 50 mL) and the combined
organic layers were washed with a water solution of Na2CO3 (3 x 30 mL), dried (Na2SO4) and
the solvent evaporated. The residue was purified by bulb-to-bulb distillation to yield the product
acid as an almost colourless oil (17 mmol, 89%). The analytical data were accordingly to those
reported in the literature (Tolasch et al. 2007).
7-metyloctanoic acid
The product acid was synthesized as above for (Z)-4-decenoic acid, but starting from 7methyloctan-1-ol. The analytical data were accordingly to those reported in the literature
(Tolasch et al. 2007).
7-Methyloctyl (Z)-4-decenoate
(Z)-4-decenoic acid (0.46 g, 2.71 mmol) in SOCl2 (2.2g, 1.4 mL, 18.9 mmol) was refluxed for 1
h. The excess SOCl2 was then removed by distillation and the obtained acid chloride was then
distilled bulb-to-bulb and immediately used in the next step. The acid chloride (0.51 g, 2.71
mmol) in CH2Cl2 (4 mL) was added drop-wise to a stirred solution of 7-methyloctan-1-ol (0.50
g, 2.7 mmol) in CH2Cl2 (4 mL) and pyridine (0.255 g, 3.0 mmol) under argon atmosphere. The
reaction was stirred overnight, during which it becomes slightly cloudy, and was then quenched
with water. The reaction was extracted with Et2O (3 x 20 mL) and the combined organic layers
were dried (MgSO4) and the solvent evaporated. The residue was purified by flash
chromatography to yield the product ester pure (GC) as a colourless oil (2.38 mmol, 88%). The
analytical data were accordingly to those reported in the literature (Tolasch et al. 2007).
7-Methyloctyl octanoate
The product ester was synthesized as above for 7-methyloctyl (Z)-4-decenoate but starting from
7-methyloctan-1-ol and octanoic acid. The analytical data were accordingly to those reported in
the literature (Tolasch et al. 2007).
7-Methyloctyl 7-methyloctanoate
The product ester was synthesized as above for 7-methyloctyl (Z)-4-decenoate, but starting from
7-methyloctan-1-ol and 7-metyloctanoic acid. The analytical data were accordingly to those
reported in the literature (Tolasch et al. 2007).
7-Methyloctyl 5-methylhexanoate
The product ester was synthesized as above for 7-methyloctyl (Z)-4-decenoate, but starting from
7-methyloctan-1-ol and 5-methylhexanoic acid. The analytical data were accordingly to those
reported in the literature (Tolasch et al. 2007).