In a one-step procedure, various
Terpenes, the major constituents of essential oils, present a class of natural products which are cheap and abundantly available. This pool of chiral substances can be transformed into valuable substances of considerable interest mostly for the industrial production of pharmaceuticals, cosmetics, fragrances, perfumes, and flavors, besides useful synthetic intermediates and chiral building blocks [
There is a vast literature on catalytic transformations of terpenes for a broad variety of purposes. These transformations include isomerization, oxidation, hydration, condensation, hydroformylation, hydrogenation, cyclization, rearrangement, and ring contraction or enlargement [
The preparation of
Recently, we have described an efficient process for the preparation of vic-aminoalcohols directly from simple alkenes in good yields [
NMR studies were performed on Bruker Avance 300 and Bruker Avance DRX 400 spectrometers in CDCl3, chemicals shifts are given in ppm relative to the solvent CDCl3 (7.27 ppm (1H); 77.0 ppm (13C)), and coupling constants (
The parameters of the GC program were injector 250°C and FID 320°C; the temperature ramp started at 60°C for 3 min, then it was raised with 10°C/min up to 160°C and with 5°C/min up to 260°C. It was left at 260°C for 7 min; column pressure 138.8 kPa, column flow 3.02 mL/min; linear velocity 39.5 cm/s; total flow 50.7 mL/min. Conversion and yield were calculated using dodecane as the internal standard. Analytical thin layer chromatography (TLC) was conducted on Merck aluminium plates 60 F-254 with 0.2 mm layer of silica gel. Most reagents and solvents used in the experiments were purchased from commercial sources. SiZr30, Ti-SBA 15, and SBA 15 were synthesized according to literature procedures [
In a typical experiment,
First, the respective bromoalcohols were prepared by the method described above. Then, in the same reactor, two equivalents of amine were added and the resulted mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (3 × 10 mL). The combined organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. Pure epoxide was obtained by column chromatography over silica gel using a mixture of EtOAc-heptane (2 : 8, v/v) and characterized by mass spectrometry, ATR-IR, MS/ESI measurements, and NMR spectroscopy. Characterization data can be found in ESI.
The structures of
In connection with our ongoing effort to prepare aminoalcohols from terpenes, we first focused on the optimization of bromohydrin synthesis to improve published results regarding limonene substrates. In general, it is a reaction that proceeds at a yield of 70–87% [
Synthesis of limonene bromoalcohol.
Limonene
Influence of the catalyst on the bromohydroxylation of
Entry | Catalyst | Remarks | Conversion (%) | Yield of |
---|---|---|---|---|
1 | SiO2 | 60 Å, 70–230 mesh | 79 | 64 |
2 | SIRAL 1 | Al2O3/SiO2 99 : 1, 280 m2/g | 81 | 65 |
3 | Aerosil 300 | SiO2, 300 m2/g | 87 | 51 |
4 | SiZr30 | SiO2/ZrO2 = 30, 573 m2/g | 85 | 62 |
5 | Zeolite beta, H+ form | ZEO cat PBH, SiO2/Al2O3 25–60, 600 m2/g | 83 | 57 |
6 | Ti-SBA15 | SiO2/TiO2 = 30, 668 m2/g | 78 | 61 |
7 | SBA 15 | SiO2, 850 m2/g | 82 | 62 |
8 | TiO2 | Hombikat UV 100 (anatase), 250 m2/g | 81 | 50 |
9 | Zeolite Y, H+ form | CBV 720 (Zeolyst), SiO2/Al2O3 = 30, 780 m2/g, | 86 | 55 |
10 | ZrO2 | Monoclinic phase, (Alfa Aesar), 90 m2/g | 81 | 66 |
11 | CeO2 | Nanopowder (Aldrich), particle size ≤ 25 nm | 82 | 70 |
12 | Dowex Marathon A | Cl− form (Aldrich), 1.3 meq/mL, | 76 | 70 |
13 | Montmorillonite K-10 | Powder, (Aldrich), 250 m2/g | 84 | 58 |
14 | None | 60 | 40 |
Reaction conditions: limonene 0.4 g, NBS 1.3 equiv., catalyst 0.04 g, 5 mL acetone/H2O 4 : 1 (v/v), r.t., 15 min. Conversion and yield were calculated by GC analysis using dodecane as the internal standard.
As depicted in Table
The effect of NBS was also evaluated (Table
Effect of NBS amount on bromohydroxylation of
Entry | NBS (equiv.) | Conversion (%) | Yield of |
---|---|---|---|
1 | 1 | 61 | 54 |
2 | 1.1 | 69 | 56 |
3 | 1.3 | 76 | 70 |
4 | 1.4 | 89 | 67 |
5 | 1.5 | 95 | 68 |
6 | 1.6 | 98 | 68 |
7 | 1.7 | 100 | 57 |
8 | 2 | 100 | 43 |
Reaction conditions:
The yield of bromoalcohol
Solvent effect on the bromohydroxylation of
Entry | Solvent | Conversion (%) | Yield of |
---|---|---|---|
1 | Acetone | 76 | 70 |
2 | Acetonea | 89 | 82 |
3 | MeOH | 88 | 79b |
4 | DMSO | 84 | 63 |
5 | THF | 80 | 63 |
6 | Nitromethane | 75 | 26 |
7 | Acetonitrile | 72 | 49 |
8 | Dichloroethane | 55 | 23 |
Reaction conditions:
Subsequently, the influence of the catalyst amount was also studied (Table
Influence of the catalyst amount on the bromohydroxylation of
Entry | Catalyst (g) | Conversion (%) | Yield of |
---|---|---|---|
1 | 0.03 | 89 | 67 |
2 | 0.04 | 89 | 82 |
3 | 0.06 | 81 | 65 |
4 | 0.08 | 77 | 61 |
5 | None | 60 | 40 |
Reaction conditions:
The aim of this reaction sequence was the synthesis of vicinal limonene aminoalcohol in one-pot procedure via
Synthesis of epoxide
Amine effect on the synthesis of epoxide
Entry | Amine | Conversion (%) | Yield of |
---|---|---|---|
1 | Aniline | 50 | 0 |
2 | Diethylaminea | 92 | 82 |
3 | Diethylamineb | 90 | 87 |
4 | 1-Phenylethylamine | 71 | 38 |
5 | 1-Phenylethylaminec | 69 | 31 |
6 | Morpholine | 94 | 48 |
7 | Ammonia | 90 | 33 |
Reaction conditions:
As seen in Table
After optimization of reaction conditions using limonene, and to assess the scope and limitation of the reaction, we extended this methodology to a variety of natural terpenes such as citronellol, geraniol, carvone, citronellal, citral, and
In a first series of experiments, the terpenes
Bromohydroxylation and epoxidation of natural terpenes.
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Entry | Terpenes |
Bromoalcohols |
Isolated yield |
Epoxides |
Isolated yield | |
1 |
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|
93 |
|
70 |
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2 |
|
|
|
78 |
|
60 |
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3 |
|
|
|
80 |
|
60 |
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4 |
|
|
|
64 |
|
65 |
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5 |
|
|
|
50 | — | |
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|
Reaction conditions: terpene 0.4 g, NBS 1.3 equiv.; diethylamine 2 equiv., catalyst (Dowex Marathon A, Cl− form) 0.04 g, 5 mL acetone/H2O 4 : 1 (v/v), r.t.
The catalytic synthesis of
NMR spectra of synthesized terpene derivatives and the device types used for recording spectra and other analytical data used to support the findings of this study are included within the supplementary materials.
The authors confirm that this article content have no conflicts of interest.
The authors are grateful to DAAD for financial support and fellowships. The authors thank Leibniz-Institut für Katalyse (LIKAT Rostock) for infrastructure facilities.
Figure S1: 1H NMR spectrum of 6-bromo-3,7-dimethyl-octane-1,7-diol (bromoalcohol from citronellol)