Acylation of Chiral Alcohols: A Simple Procedure for Chiral GC Analysis

Oromí-Farrús, Mireia; Torres, Mercè; Canela, Ramon

doi:https://doi.org/10.1155/2012/452949

Journal of Analytical Methods in Chemistry

On this page

Abstract Introduction Experimental Results and Discussion Conclusions Appendix Acknowledgments References Copyright Related Articles

Research Article | Open Access

Volume 2012 | Article ID 452949 | https://doi.org/10.1155/2012/452949

Acylation of Chiral Alcohols: A Simple Procedure for Chiral GC Analysis

Mireia Oromí-Farrús,¹Mercè Torres,²and Ramon Canela¹

Academic Editor: Boryana M. Nikolova-Damyanova

Received30 Nov 2011

Revised04 Feb 2012

Accepted15 Feb 2012

Published09 May 2012

Abstract

The use of iodine as a catalyst and either acetic or trifluoroacetic acid as a derivatizing reagent for determining the enantiomeric composition of acyclic and cyclic aliphatic chiral alcohols was investigated. Optimal conditions were selected according to the molar ratio of alcohol to acid, the reaction time, and the reaction temperature. Afterwards, chiral stability of chiral carbons was studied. Although no isomerization was observed when acetic acid was used, partial isomerization was detected with the trifluoroacetic acid. A series of chiral alcohols of a widely varying structural type were then derivatized with acetic acid using the optimal conditions. The resolution of the enantiomeric esters and the free chiral alcohols was measured using a capillary gas chromatograph equipped with a CP Chirasil-DEX CB column. The best resolutions were obtained with 2-pentyl acetates () and 2-hexyl acetates (). This method provides a very simple and efficient experimental workup procedure for analyzing chiral alcohols by chiral-phase GC.

1. Introduction

Chiral alcohols occur as natural products and frequently as intermediates in the synthesis of chiral molecules, most of them in the field of synthetic pharmaceuticals possessing chiral centres [1–3]. In pharmacy the use of enantiopure new drugs will certainly increase due to the often well-documented different biological activities of enantiomers. Moreover, the pharmacokinetics or toxicology of each enantiomer with regard to the drug dosage or side effects is significantly different and consequently so are the resulting regulatory requirements [4, 5]. The determination of the enantiomeric excess (% ee) is therefore critical to the progress of these fields, so many methods have been developed for determining the degree of enantiomeric purity of chiral alcohols in the yield of chromatography and electrophoresis [6–12]. Nowadays, gas-liquid chromatography on chiral stationary phases, especially per-0-modified cyclodextrins, plays the dominant role for the chiral separation of a wide range of volatile compounds due to its ease of use and the commercial availability of columns [13]. However, many of these methods for determining the degree of enantiomeric purity of chiral alcohols are improved when these compounds are converted into volatile esters, such as acetate or trifluoroacetate. Acylation reduces polarity and enhances the separation of chiral compounds in the chromatographic column, as well as conferring better volatility. Typically, only derivatization with acetyl groups or with fluorinated acyl groups up to heptafluorobutyryl improves volatility [14].

Acylation of alcohols is among the most frequently used processes in organic synthesis. Although different methods are described in the literature [15–20], some of them are less effective or ineffective for secondary and tertiary alcohols, others are moisture sensitive or highly expensive, and they may even be potentially explosive (e.g., perchlorates or perchloric acid).

Various acylation reactions using iodine as catalyst have been reported [21–26]. Ramalinga and coworkers described iodine as a Lewis catalyst for the esterification and transesterification of acids using an excess of alcohol under reflux conditions [27]. Chavan and coworkers described the transesterification in toluene of β-ketoesters with some primary, secondary alcohols and phenols using iodine as a catalyser in the presence of zinc as a mediator [28]. Afterwards, they described that even iodine acts as an efficient catalysts for transesterification reactions; however, phenols did not undergo transesterification [29]. A procedure for the acetylation of alcohols, amines and phenols with isopropenyl acetate and iodine as a catalyser under solvent-free conditions were described by Ahmed and van Lier [30]. This procedure gave acetone as a by-product.

Recently, Jereb and coworkers have demonstrated that iodine is an efficient catalyst for esterification under solvent-free conditions for several alcohols [31].

We describe herein a simple and convenient procedure for acylation of chiral alcohols under solvent-free conditions in the presence of a catalytic amount of iodine with no by-products formation and using near equimolar amounts of alcohol and carboxylic acid (Scheme 1). Initially, a systematic study was carried out for catalytic evaluation of iodine in the acetylation of 2-heptanol. Further, the optimized method was applied to (R)-2-heptanol and cis-1,3-cyclohexanediol to determine that no isomerization occurred with acetylation or trifluoroacetylation. Finally, it was applied to a variety of chiral alcohols. All the esters were analyzed by gas chromatography on a CP Chirasil-DEX CB column in order to provide optimum resolution for a chiral alcohol of a particular structural type.

2. Experimental

2.1. Reagents

3-Hexanol (4), 4-methyl-2-pentanol (5), 3-methylcyclopentanol (9), 3-methylcyclohexanol (10), 2-tert-butylcyclohexanol (11), 2-methylcyclopentanol (12), 4-methylcyclohexanol (13), 2-chlorocyclohexanol (14), 2,6-dimethylcyclohexanol (15), 4-tert-butylcyclohexanol (16), 3,3,5-trimethylcyclohexanol (17), 2-phenylcyclohexanol (18), DL-menthol (19), 1,2-cyclohexanediol (20), 1,3-cyclohexanediol (21), iodine, and acetic acid were all from Acros Organics, Barcelona, Spain. 2-Butanol (1), S-2-butanol, 2-hexanol (3), S-2-hexanol, trans-S,S-1,2-cyclohexanediol, trans-R,R-1,2-cyclohexanediol, 2-heptanol (6), R-2-heptanol, (+)-menthol, and tert-butanol were purchased from Fluka, Madrid, Spain. 2-Octanol (7), 3-octanol (8), and cis-1,2-cyclohexanediol were from Sigma-Aldrich, Madrid, Spain. 2-Pentanol (2) was acquired from Merck, Barcelona, Spain. 1-Methylhexyl acetate was obtained by stirring at 100°C for 48 h in a screw-cap vial a mixture of 2-heptanol (20 mmol), acetic acid (200 mmol), iodine (0.6 mmol) and anh. Na₂SO₄ (0.2 mmol). Afterwards, 25 mL of hexane were added and the mixture was filtered. The organic solution was washed with saturated sodium thiosulfate solution, saturated NHCO₃ solution, and water. Hexane was stripped off by distillation at 69°C at atmospheric temperature and the 1-methylhexyl acetate was obtained. The product was characterized by NMR ¹H and ¹³C.

2.2. Procedures

2.2.1. Optimization of the Derivatization Step

Mixtures of 2-heptanol (2 mmol), acetic acid at different molar ratios (2, 3, 4, 12, and 20 mmol) containing iodine (0.06 mmol) and tridecane (4 mmol) as internal standard, anh. Na₂SO₄ (0.02 mmol) either without solvent or dissolved in 0.5 mL (7 mmol) tert-butanol were stirred at different temperatures (100, 120, and 140°C) for different reaction times (4, 8, 24 and 48 h) in 3 mL amber screw-cap vials. The reaction product was dissolved in 1 mL dichloromethane and filtered. The filtrate was used for GC analysis directly and analysed in a DB-Wax capillary column as described in the following. Reactions were carried out in triplicate.

2.2.2. Derivatization

A mixture of alcohol (2 mmol), either acetic acid or trifluoroacetic acid (3 mmol, iodine (0.06 mmol), and anh. Na₂SO₄ (0.02 mmol)) were stirred at 100°C for 48 h in a 3 mL amber screw-cap vial. The reaction product was dissolved in 1 mL dichloromethane, filtered and analysed by both GC/MS and chiral phase GC analysis as described in what follows. Reactions were carried out in duplicate.

2.2.3. Chromatographic Conditions

No Chiral-Phase GC Analysis
GC-FID analyses were carried out in a Trace 2000 series (ThermoQuest) GC with a DB-Wax (polyethylene glycol) capillary column of 30 m × 0.25 mm diameter, 0.25 μm film thickness. Helium (1 mL/min) was used as the carrier gas. 250°C, 275°C. The GC temperature was programmed at 70°C and ramped first at 5°C/min to 160°C and later at 10°C/min to 200°C.

Chiral-Phase GC Analysis
The column used was CP Chirasil-DEX CB Varian (modified β-cyclodextrins bonded to a dimethylpolysiloxane) (25 m × 0.25 mm diameter, 0.25 μm film thickness). Hydrogen (80 cm/s) was used as the carrier gas. 230°C, 250°C. The separation factor, α, was calculated according to IUPAC [32].

2.2.4. RMN

¹H and ¹³C NMR spectra were recorded on a Varian AS400 spectrometer, operating at 400 MHz.

2.3. Statistical Analysis

Linear model analysis of variance (ANOVA) and the Tukey-Kramer pairwise differences adjustment method was carried out by the SAS software version 9.0 (SAS Institute, Inc). All the statistical tests applied in this work were employed to determine the statistical differences among 1-methylhexyl acetate yields when reaction optimizations were carried out.

3. Results and Discussion

First of all, the acetylation was studied with the presence of a tertiary alcohol, tert-butanol, or without solvent, at various molar ratios alcohol : acetic acid with 1 equiv. of acetic acid in the presence of 3 mol % of iodine at 100°C for 24 and 48 h (Table 1). Clearly, tert-butanol makes the reaction slower, needing a 1 : 6 molar ratio and 48 h (entry 11). We obtained the maximum yield at a 1 : 2 molar ratio for 24 h without using any solvent (entry 1). Similar behaviour has also been described by Jereb and coworkers [31] using dichloromethane as solvent. They carried out the same reaction with other alcohols using a 1 : 3 molar excess of acetic acid in a free solvent system. The addition of dichloromethane as solvent also provoked a decrease of the reaction rate.

Then, we investigated the influence of lower molar ratios alcohol : acetic acid and different reaction times in a solvent-free system (Table 2). With a 1 : 1 molar ratio alcohol : acid the best yield was obtained after 48 h reaction (entry 2). With 1 : 1.5 and 1 : 2 molar ratios acetylation only required half the time (24 h) to obtain no statistically different results (entries 4, 8). Remarkably in terms of atom economy, a 1 : 1 molar ratio was sufficient, but a longer reaction time was needed to reach a high yield. In order to shorten the reaction times, complementary studies were carried out, increasing the reaction temperature (Table 3). However, the yield of 1-methylhexyl acetate decreased when the temperature increased.

We decided to carry out the subsequent reactions using a 1 : 1.5 molar ratio alcohol : acid at 100°C for 24 h in a solvent-free system. However, considering that the main target was to determine the % ee of a chiral alcohol, it could be not necessary to achieve a high yield of acetylation. Therefore, an equimolecular molar ratio alcohol : acid at 100°C for 4 h could be sufficient. This method is a simple and greener alternative to conventional methods that typically are performed with activated carboxylic acid derivatives such as acid anhydrides, acid chlorides, acyl imidazoles, or acylureas, which need the presence of tertiary amines such as triethylamine, pyridine, or DMAP [15–20]. Moreover, any solvent was needed [28, 29], there were not any byproducts formation [30], and an equimolar amount of reactives can be used [31].

According to these results, we proved the stability of the chiral carbons in the selected conditions. Figures 1 and 2 show the results obtained after acetylation of racemic 2-heptanol and (R)-2-heptanol. Similar results were obtained using trans-1,3-cyclohexanediol and cis-1,3-cyclohexanediol (Figures 3, 4, and 5), indicating that the derivatization process did not cause any isomerization of the chiral carbons of the two molecules. Jereb and coworkers also studied the stereochemical behaviour of some secondary cyclic aliphatic alcohols and 1-phenylethanols in their acetylation reactions with iodine as a catalyst. The aliphatic cyclic alcohols studied yielded esters with retention of stereochemistry, but a loss of stereochemical integrity was observed in chiral 1-phenylethanols. No data was provided about the behaviour of acyclic secondary alcohols or diols in these conditions [31]. Moreover, we also studied the stability of these chiral carbons using trifluoroacetic acid instead of acetic acid. In this case, a partial isomerization was observed making unsuitable this acid for acylation (results not showed).

Afterwards, three series of alcohols were tested with this acylation method to determine the applicability of the method to study the stereochemical ratio between isomers. The improvement in the separation factors (α) related to the free alcohols was determined. A resolution factor of 1.5 or greater indicates baseline enantiomeric resolution [13].

Table 4 shows the results when acyclic alcohols were derivatized. Acetylation increased the separation factor of the majority of the tested alcohols. The best α was obtained with 2-pentyl acetates that have a separation factor value of 3.00 compared with the 1.07 corresponding to the free alcohols. To our knowledge no better α are described in the literature for the 2-pentyl acetates. Higher α increases were also observed for 2-butanol acetate derivatives (1.44 compared with 1.05), 2-hexanol acetate derivatives (1.95 compared with 1.05) and 2-octanol acetate derivatives (1.50 compared with 1.02). Acetylation also allowed the two enantiomers of 2-heptanol and 3-octanol to be separated. Smith and Simpson [33] investigated the separation of enantiomers of these acyclic alcohols on a γ-trifluoroacetylated cyclodextrin phase at 35°C, showing for the majority of them an α value similar to or lower than those obtained in our β-cyclodextrin column and lower than our corresponding acylated derivatives.

The elution order of the acetylated enantiomers of some alcohols, entries 2, 4, 6,7, and 8, was assumed from the literature [34, 35]. We would remark that the elution order of (−)-enantiomers and (+)-enantiomers depends on some factors such as cyclodextrin type (α, β, γ: on a β-CD derivative all (−)-enantiomers eluted before the (+)-enantiomers), the stereoconfiguration of the product (it can have a dominant influence on chiral interactions, leading to the reversal of the elution order), cyclodextrin derivative types, and temperature. Moreover, some studies indicate that the retention of enantiomers is correlated with optical activity [36].

Table 5 shows the results when mono- and polysubstituted cyclic alcohols were derivatized. Derivatization usually allows to separate the stereoisomers not resolved as free alcohols. Acylation with acetic acid allows the four stereoisomers of 3-methyl-1-cyclopentanol (entry 1), 3-methyl-1-cyclohexanol (entry 2), and 2-tert-butyl-1-cyclohexanol (entry 3) to be separated. Moreover, acetylation of 2-chloro-1-cyclohexanol (entry 6) and 4-tert-butyl-1-cyclohexanol (entry 7) increases the separation factor.

When the acylation method was applied to polysubstituted cyclic alcohols, the results were not as good as previous ones. Now, only acetylation of D,L-menthol produced an increase in the separation factor value of the two enantiomers. Both stereoisomers have been already acetylated by Jereb and coworkers using a similar method [31]. They have already demonstrated that any isomerization was provoked in both compounds when acetylated separately. The α value was higher than the α obtained in some α, β, and γ permethylated cyclodextrins [13, 33] and in stationary GC phases of other cyclodextrin derivatives [39–41].

Finally the acylation method was applied to three diols: 1,2-octanediol, 1,2-cyclohexanediol, and 1,3-cyclohexanediol (Table 6). Now, one or both hydroxyl groups can be acetylated. In order to determine the retention time of the mono and diacetylated stereoisomers, two acylations reactions were carried out, one with a 1 : 4 molar ratio alcohol : acid and the other with a 1 : 1.5 molar ratio. When the molar ratio alcohol : acid was 1 : 1.5, there were more molecules with only one hydroxyl group acetylated than with the two hydroxyl groups acetylated (Figures 3, 4 and 5). However, when the molar ratio was 1 : 4, the numbers of diacetylated molecules were higher than the monoacetylated molecules. The samples were also analysed by NMR and the ¹H and ¹³C spectra were in concordance with the chromatograms. The acetylation of one hydroxyl group increased the α value, compared with their corresponding alcohols; moreover, the α value was higher when both hydroxyl groups were acetylated. Thus, the diacetylation of 1,2-octanediol produced an increase in the separation factor value of the two enantiomers (1.03 for the diol and 1.34 for the diacetylated derivative).

Li et al. obtained a similar α value (1.05) for the 1,2-octanediol on a β-2,6-di-O-pentyl-3-O-trifluoroacetylated cyclodextrin but lower than the separation of mono- and diacetates in our column [43]. The acetylation of trans-1,3-cyclohexanediol allowed the separation of its stereoisomers and the two sets of 1,2-cyclohexanediol stereoisomers were separated when acetylation of one of the hydroxyl groups took place. The cis-1,3-cyclohexanediol is a meso-form. However, when one of the hydroxyl groups was acetylated one chiral carbon was formed and the enantiomers could be separated in the column. When both hydroxyls groups were acetylated, the compound was again a meso-form. Finally, we would like to point out the simple handling of the reaction carried out prior to the GC analysis. Any further treatment is not needed once the reaction is finished but dilution and filtration of the reaction crude. Any loss of resolution capacity has not been observed in the chromatographic column after carrying out all of the described studies.

4. Conclusions

We have demonstrated that the present procedure with iodine/carboxylic acid without adding solvent provides a very efficient method of esterification of numerous acyclic and cyclic chiral alcohols. This procedure allows a fast analysis of these compounds by chiral-phase GC. The main advantages of this method are its operational simplicity, the ready availability, and nontoxic nature of the reagent, and its general applicability. Near equimolar amounts of alcohol and carboxylic acid are typically used, thus avoiding waste and providing very simple experimental and workup procedures. Furthermore, acetylation of acyclic and cyclic alcohols usually increases the separation factor of the isomers.

Appendix

NMR Data of the Acetylated Alcohols, Analysed by a Varian 400, Solvent Acetone-d

1-Ethylbutyl Acetate
¹H NMR (400 MHz, acetone) δ 4.81–4.72 (m, 1H), 1.99 (s, 3H), 1.63–1.44 (m, 4H), 1.41–1.22 (m, 2H), 0.89 (t, J = 7.47, Hz 3H), 0.85 (t, Hz, 3H). ¹³C NMR (101 MHz, acetone) δ 170.08, 74.31, 35.71, 26.85, 20.14, 18.35, 13.33, 9.02.

1-Methylheptyl Acetate
¹H NMR (400 MHz, acetone) δ 4.89–4.76 (m, 1H), 1.96 (s, 3H), 1.60–1.43 (m, 2H), 1.28 (m, 8H), 1.16 (d, Hz, 3H), 0.88 (t, Hz, 3H). ¹³C NMR (101 MHz, acetone) δ 169.65, 70.17, 35.73, 31.59, 29.15, 25.19, 22.34, 20.28, 19.35, 13.43.

1-Ethylhexyl Acetate
¹H NMR (400 MHz, acetone) δ 4.76 (dt, , 6.2 Hz, 1H), 1.98 (s, 3H), 1.63–1.46 (m, 4H), 1.37–1.21 (m, 6H), 0.88 (t, ,46 Hz, 3H), 0.86 (t, Hz, 3H). ¹³C NMR (101 MHz, acetone) δ 169.86, 74.64, 33.46, 31.52, 26.80, 24.83, 22.30, 20.14, 13.37, 9.01.

cis-3-Methylcyclopentyl Acetate
¹H NMR (400 MHz, acetone) δ 3.90 (m, 1H), 1.93 (s, 3H), 1.98 (m, 1H), 1.68 (m, 1H), 1.59–1.49 (m, 3H), 1.29 (m, 1H), 1.16 (m, 1H), 0.98 (d, 3H). ¹³C NMR (101 MHz, acetone) δ 169.70, 76.14, 41.16, 32.76, 32.36, 32.30, 20.27 CH3, 20.24.

trans-3-Methylcyclopentyl Acetate
¹H NMR (400 MHz, acetone) δ 5.07 (m, 1H), 1.94 (s, 3H), 1.83–1.72 (m, 2H), 1.64–1.53 (m, 2H), 1.43–1.30 (m, 2H), 1.22–1.11 (m, 1H), 1.02 (dd, , 4.0 Hz, 3H). ¹³C NMR (101 MHz, acetone) δ 169.75, 76.16, 40.78, 32.84, 32.38, 32.33, 20.11, 19.52.

trans-2-Methylcyclopentyl Acetate
¹H NMR (400 MHz, acetone) δ 4.62 (dt, , 4.6 Hz, 1H), 1.96 (m, 1H), 1.96 (s, 3H), 1.71–1.61 (m, 3H), 1.59–1.49 (m, 2H), 1.20 (m, 1H), 0.97 (d, Hz, 3H). ¹³C NMR (101 MHz, acetone) δ 169.94, 82.07, 39.86, 31.56, 31.04, 22.06, 20.21, 17.53.

cis-2-Methylcyclopentyl Acetate
¹H NMR (400 MHz, acetone) δ 4.81 (m, 1H), 1.97 (m, 1H), 1.97 (s, 3H), 1.68–1.57 (m, 3H), 1.53–1.43(m, 2H), 1.17 (m, 1H), 0.96 (d, Hz, 3H). ¹³C NMR (101 MHz, acetone) δ 169.92, 80.21, 39.38, 32.43, 332.17, 22.22, 20.19, 17.52.

cis-3-Methylcyclopentyl Acetate
¹H NMR (400 MHz, acetone) δ 4.98 (m, 1H), 1.98 (s, 3H), 1.93–1.86 (m, 2H), 1.65–1.35 (m, 2H), 1.30–1.13 (m, 2H), 1.02 (m, 1H), 0.86 (d, Hz, 3H), 0.87 (m, 2H). ¹³C NMR (101 MHz, acetone) δ 169.44, 69.51, 38.12, 33.89, 31.20, 30.51, 26.87, 21.54, 20.40.

trans-3-Methylcyclopentyl Acetate
¹H NMR (400 MHz, acetone) δ 4.61 (tt, , 4.3 Hz, 1H), 1.94 (m, 3H), 1.93–1.87 (m, 2H), 1.68–1.12 (m, 5H), 0.91 (d, , 3H), 0.89 (m, 2H). ¹³C NMR (101 MHz, acetone) δ 169.42, 72.49, 40.36, 35.36, 33.80, 31.13, 23.69, 21.68, 20.32.

trans-4-Methylcyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 4.57 (tt, , 4.4 Hz, 1H), 1.94 (s, 3H), 1.77–1.66 (m, 2H), 1.45–1.24 (m, 5H), 1.10–0.99 (m, 2H), 0.88 (d, Hz, 3H). ¹³C NMR (101 MHz, acetone) δ 169.49, 72.65, 32.48, 31.52, 31.45, 21.25, 20.33.

cis-4-Methylcyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 4.89 (s, 1H), 1.98 (s, 3H), 1.92–1.84 (m, 2H), 1.82–1.68 (m, 2H), 1.52 (m, 3H), 0.95 (m, 2H), 0.90 (d, Hz, 3H). ¹³C NMR (101 MHz, acetone) δ 169.45, 69.01, 32.22, 31.52, 31.14, 21.25, 21.45.

cis-4-tert-Butylcyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 4.55 (m, 1H), 1.94 (s, 3H), 1.81 (m, 2H), 1.36–0.98 (m, 7H), 0.86 (s, 9H). ¹³C NMR (101 MHz, acetone) δ 169.48, 72.97, 68.63, 47.03, 36.06, 31.95, 27.00, 20.32.

trans-4-tert-Butylcyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 4.92 (m, 1H), 1.99 (s, 3H), 1.89 (m, 4H), 1.54–1.40 (m, 2H), 1.20–0.98 (m, 3H), 0.86 (s, 9H). ¹³C NMR (101 MHz, acetone) δ 169.45, 72.97, 69.95, 47.42, 36.01, 31.89, 26.86, 20.82.

cis-3,3,5-Trimethylcyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 4.83 (tt, , 4.4 Hz, 1H), 1.94 (s, 3H), 1.93–1.89 (m, 1H), 1.78–1.62 (m, 1H), 1.35 (ddt, , 3.8, 2.0 Hz, 2H), 1.08 (m, 2H), 0.94 (s, 6H), 0.90 (d, Hz, 3H), 0.96–0.78 (m, 1H). ¹³C NMR (101 MHz, acetone) δ 169.60, 70.21, 47.23, 43.82, 40.25, 32.45, 31.79, 26.91, 24.88, 21.74, 20.37.

trans-3,3,5-Trimethylcyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 5.02 (s, 1H), 1.96 (s, 3H), 1.90 (m, 1H), 1.78–1.61 (m, 2H), 1.47–1.39 (m, 1H), 1.06–0.77 (m, 3H), 0.89 (d, Hz, 3H), 0.88 (s, 6H). ¹³C NMR (101 MHz, acetone) δ 169.34, 70.17, 47.81, 40.87, 38.08, 33.38, 30.26, 26.76, 23.22, 21.93, 20.49.

2-Hydroxyoctyl Acetate
¹H NMR (400 MHz, acetone) δ 4.01–3.88 (m, 2H), 3.43 (m, 1H), 2.00 (s, 3H), 1.52–1.18 (m, 10H), 0.88 (t, Hz 3H). ¹³C NMR (101 MHz, acetone) δ 170.12, 71.14, 69.12, 33.56, 31.68, 29.16, 25.08, 22.35, 19.88, 13.44.

1-(Hydroxymethyl)heptyl Acetate
¹H NMR (400 MHz, acetone) δ 4.85 (m, 1H), 3.55 (m, 2H), 1.99 (s, 3H), 1.65–1.20 (m, 10H), 0.88 (t, Hz 3H). ¹³C NMR (101 MHz, acetone) δ 169.90, 75.81, 68.34, 31.56, 30.47, 29.03, 25.63, 22.38, 20.20, 13.45.

1-[(Acetyloxy)methyl]heptyl Acetate
¹H NMR (400 MHz, acetone) δ 5.01(m, 1H), 4.21 (dd, , 3.4 Hz, 1H), 4.5-3,93 (m, 1H), 1.99 (s, 3H), 1.98 (s, 3H), 1.65–1.20 (m, 10 H), 0.88 (t, Hz 3H). ¹³C NMR (101 MHz, acetone) δ 169.98, 169.79, 74.67, 68.66, 31.62, 30.40, 28.84, 24.90, 22.31, 20.03, 19.73, 13.41.

cis-2-Hydroxycyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 4.82 (dd, , 4.0 Hz, 1H), 4.37 (s, OH), 4.04 (m, 1H), 1.99 (s, 3H), 1.82 (m, 1H), 1.77–1.61 (m, 4H), 1.31 (m, 2H), 1.41–1.21 (m, 1H). ¹³C NMR (101 MHz, acetone) δ 169.76, 73.31, 67.99, 29.54, 28.08, 21.90, 21.15, 20.62.

cis-2-(Acetyloxy)cyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 4.96 (d, Hz, 2H), 1.97 (s, 6H), 1.80 (m, 2H), 1.69–1.59 (m, 2H), 1.53–1.40 (m, 4H). ¹³C NMR (101 MHz, acetone) δ 169.49, 73.78, 29.54, 27.30, 20.09.

trans-2-Hydroxycyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 4.53 (d, Hz, 1H), 3.49 (m, 1H), 3.30 (s, OH), 1.97 (s, 3H), 1.91 (m, 2H), 1.76–1.59 (m, 2H), 1.39–1.16 (m, 4H). ¹³C NMR (101 MHz, acetone) δ 169.45, 77.15, 71.09, 32.88, 23.60, 3.04, 20.09, 19.64.

trans-2-(Acetyloxy)cyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 4.72 (m, 2H), 1.95 (s, 6H), 1.92 (m, 2H), 1.64 (m, 2H), 1.243–1.23(m, 4H). ¹³C NMR (101 MHz, acetone) δ 169.97, 73.05, 29.66, 23.44, 20.10.

cis-3-Hydroxycyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 4.62 (m, 1H), 3.57 (m, 1H), 4.86 (s, OH), 1.95 (s, 3H), 1.93–1.77 (m, 1H), 1.77–1.61 (m, 1H), 1.61–1.46 (m, 2H), 1.45–1.31 (m, 3H), 1.31–1.06 (m, 1H). ¹³C NMR (101 MHz, acetone) δ 169.34, 70.89, 65.75, 38.70, 36.92, 30.27, 20.21, 18.86.

trans-3-Hydroxycyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 5.01 (m, 1H), 3.96 (m, 1H), 4.86 (s, OH), 1.98 (s, 3H), 1.93–1.77 (m, 1H), 1.77–1.61 (m, 1H), 1.61–1.46 (m, 2H), 1.45–1.31 (m, 3H), 1.31–1.06 (m, 1H). ¹³C NMR (101 MHz, acetone) δ 169.43 C, 69.93, 65.58, 41.29, 35.20, 29.82, 20.29, 19.00.

cis-3-(Acetyloxy)cyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 4.69 (m, 2H), 1.96 (s, 6H), 1.94–1.78 (m, 3H), 1.78–1.61 (m, 1H), 1.61–1.31 (m, 2H), 1.31–1.07 (m, 2H). ¹³C NMR (101 MHz, acetone) δ 171.09, 70.05, 34.50, 30.87, 20.38, 19.78.

trans-3-(Acetyloxy)cyclohexyl Acetate
¹H NMR (400 MHz, acetone) δ 5.06 (m, 2H), 1.96 (s, 6H), 1.94–1.78 (m, 3H), 1.78–1.61 (m, 1H), 1.61–1.31 (m, 2H), 1.31–1.07 (m, 2H). ¹³C NMR (101 MHz, acetone) δ 171.09, 69.45, 34.57, 30.47, 20.33, 19.58.

Acknowledgments

The authors are grateful to the Secretaría de Estado de Política Científica y Tecnológica of the Spanish Ministerio de Ciencia y Tecnología (CTQ2009-14699-C02-01) and Departament d’Universitats, Recerca i Societat de la Informació of the Generalitat de Catalunya (2001SGR00309) for financial support. M. Oromi-Farrús thanks the Ministerio de Educación y Cultura for the Predoctoral Fellowship no. AP 2001–3761.

References

E. J. Bourne, M. Stacey, J. C. Tatlow, and R. Worrall, “Studies of trifluoroacetic acid—part 15. Further investigations on the reactions of acyl trifluoroacetates with hydroxy-compounds,” Journal of the Chemical Society, pp. 3268–3282, 1958.
View at: Publisher Site | Google Scholar
W. Walther and T. Netscher, “Design and development of chiral reagents for the chromatographic e.e. determination of chiral alcohols,” Chirality, vol. 8, no. 5, pp. 397–401, 1996.
View at: Publisher Site | Google Scholar
M. Kataoka, K. Kita, M. Wada, Y. Yasohara, J. Hasegawa, and S. Shimizu, “Novel bioreduction system for the production of chiral alcohols,” Applied Microbiology and Biotechnology, vol. 62, no. 5-6, pp. 437–445, 2003.
View at: Publisher Site | Google Scholar
J. E. Rekoske, “Chiral separations,” AIChE Journal, vol. 47, no. 1, pp. 2–5, 2001.
View at: Publisher Site | Google Scholar
V. Schurig, “Separation of enantiomers by gas chromatography,” Journal of Chromatography A, vol. 906, no. 1-2, pp. 275–299, 2001.
View at: Publisher Site | Google Scholar
Z. Juvancz and P. Petersson, “Enantioselective gas chromatography,” Journal of Microcolumn Separations, vol. 8, no. 2, pp. 99–114, 1996.
View at: Google Scholar
J. Kang, D. Wistuba, and V. Schurig, “Recent progress in enantiomeric separation by capillary electrochromatography,” Electrophoresis, vol. 23, no. 22-23, pp. 4005–4021, 2002.
View at: Publisher Site | Google Scholar
B. Chankvetadze, “Combined approach using capillary electrophoresis and NMR spectroscopy for an understanding of enantioselective recognition mechanisms by cyclodextrins,” Chemical Society Reviews, vol. 33, no. 6, pp. 337–347, 2004.
View at: Publisher Site | Google Scholar
C. P. Kapnissi-Christodoulou, X. Zhu, and I. M. Warner, “Analytical separations in open-tubular capillary electrochromatography,” Electrophoresis, vol. 24, no. 22-23, pp. 3917–3934, 2003.
View at: Google Scholar
G. Terfloth, “Enantioseparations in super- and subcritical fluid chromatography,” Journal of Chromatography A, vol. 906, no. 1-2, pp. 301–307, 2001.
View at: Publisher Site | Google Scholar
Y. Liu, A. W. Lantz, and D. W. Armstrong, “High efficiency liquid and super-/subcritical fluid-based enantiomeric separations: an overview,” Journal of Liquid Chromatography and Related Technologies, vol. 27, no. 7–9, pp. 1121–1178, 2004.
View at: Publisher Site | Google Scholar
N. M. Maier, P. Franco, and W. Lindner, “Separation of enantiomers: needs, challenges, perspectives,” Journal of Chromatography A, vol. 906, no. 1-2, pp. 3–33, 2001.
View at: Publisher Site | Google Scholar
S. Sponsier and M. Biedermann, “Optimization of chiral separations using capillary gas chromatography,” International Chromatography Laboratory, vol. 8, pp. A–F, 1998.
View at: Google Scholar
S. C. Moldoneanu and V. David, “Chemical reactions used in derivatization. 18.3. Acetylation reactions,” Journal of Chromatography Library, pp. 569–576, 2002.
View at: Google Scholar
J. S. Fritz and G. H. Schenk, “Acid-catalyzed acetylation of organic hydroxyl groups,” Analytical Chemistry, vol. 31, no. 11, pp. 1808–1812, 1959.
View at: Google Scholar
G. Stork, T. Takahashi, I. Kawamoto, and T. Suzuki, “Total synthesis of prostaglandin F2α by chirality transfer from D-glucose,” Journal of the American Chemical Society, vol. 100, no. 26, pp. 8272–8273, 1978.
View at: Google Scholar
K. L. Chandra, P. Saravanan, R. K. Singh, and V. K. Singh, “Lewis acid catalyzed acylation reactions: scope and limitations,” Tetrahedron, vol. 58, no. 7, pp. 1369–1374, 2002.
View at: Publisher Site | Google Scholar
M. Servrin and A. Krief, “Regioselective ad [C,C] connective routes to oxetanes and tetrahydrofuranes,” Tetrahedron Letters, vol. 21, no. 6, pp. 585–586, 1980.
View at: Google Scholar
A. Orita, C. Tanahashi, A. Kakuda, and J. Otera, “Highly efficient and versatile acylation of alcohols with Bi(OTf)3 as catalyst,” Angewandte Chemie, vol. 39, no. 16, pp. 2877–2879, 2000.
View at: Publisher Site | Google Scholar
Y. Nakae, I. Kusaki, and T. Sato, “Lithium perchlorate catalyzed acetylation of alcohols under mild reaction conditions,” Synlett, no. 10, pp. 1584–1586, 2001.
View at: Google Scholar
P. Phukan, “Iodine as an extremely powerful catalyst for the acetylation of alcohols under solvent-free conditions,” Tetrahedron Letters, vol. 45, no. 24, pp. 4785–4787, 2004.
View at: Publisher Site | Google Scholar
Y. Ren and C. Cai, “Molecular iodine in ionic liquid: a green catalytic system for esterification and transesterification,” Synthetic Communications, vol. 40, no. 11, pp. 1670–1676, 2010.
View at: Publisher Site | Google Scholar
M. A. Hussain, D. Shahwar, M. N. Hassan, M. N. Tahir, M. S. Iqbalc, and M. Sher, “An efficient esterification of pullulan using carboxylic acid anhydrides activated with iodine,” Collection of Czechoslovak Chemical Communications, vol. 75, no. 1, pp. 133–143, 2010.
View at: Publisher Site | Google Scholar
H. N. Cheng, M. K. Dowd, R. L. Shogren, and A. Biswas, “Iodine-catalyzed synthesis of mixed cellulose esters,” American Chemical Society, Division of Polymer Chemistry, vol. 51, pp. 29–30, 2010.
View at: Google Scholar
A. K. Verma, T. Aggarwal, V. Rustagi, and R. C. Larock, “Iodine-catalyzed and solvent-controlled selective electrophilic cyclization and oxidative esterification of ortho-alkynyl aldehydes,” Chemical Communications, vol. 46, no. 23, pp. 4064–4066, 2010.
View at: Publisher Site | Google Scholar
R. A. Jones, R. Davidson, A. T. Tran, N. Smith, and M. Carmen Galan, “Iodine-catalyzed one-pot acetalation-esterification reaction for the preparation of orthogonally protected glycosides,” Carbohydrate Research, vol. 345, no. 13, pp. 1842–1845, 2010.
View at: Publisher Site | Google Scholar
K. Ramalinga, P. Vijayalakshmi, and T. N. B. Kaimal, “A mild and efficient method for esterification and transesterification catalyzed by iodine,” Tetrahedron Letters, vol. 43, no. 5, pp. 879–882, 2002.
View at: Publisher Site | Google Scholar
S. P. Chavan, K. Shivasankar, R. Sivappa, and R. Kale, “Zinc mediated transesterification of β-ketoesters and coumarin synthesis,” Tetrahedron Letters, vol. 43, no. 47, pp. 8583–8586, 2002.
View at: Publisher Site | Google Scholar
S. P. Chavan, R. R. Kale, K. Shivasankar, S. I. Chandake, and S. B. Benjamin, “A simple and efficient method for transesterification of β-ketoesters catalysed by iodine,” Synthesis, no. 17, pp. 2695–2698, 2003.
View at: Google Scholar
N. Ahmed and J. E. van Lier, “Molecular iodine in isopropenyl acetate (IPA): a highly efficient catalyst for the acetylation of alcohols, amines and phenols under solvent free conditions,” Tetrahedron Letters, vol. 47, no. 30, pp. 5345–5349, 2006.
View at: Publisher Site | Google Scholar
M. Jereb, D. Vražič, and M. Zupan, “Dual behavior of alcohols in iodine-catalyzed esterification under solvent-free reaction conditions,” Tetrahedron Letters, vol. 50, no. 20, pp. 2347–2352, 2009.
View at: Publisher Site | Google Scholar
IUPAC Compendium of Chemical Terminology, 2nd edition, 1997.
I. D. Smith and C. F. Simpson, “Investigation into the GC separation of enantiomers on a trifluoroacetylated cyclodextrin—1. Effect of analyte structure on stereoselectivity for alcohols,” Journal of High Resolution Chromatography, vol. 15, pp. 800–806, 1992.
View at: Google Scholar
“Chiral Cyclodextrin Capillary Columns,” Supelco Bulletin 887, 1998.
View at: Google Scholar
A Guide to the Analysis of Chiral Compounds by GC, Resteck Corporation, 1997.
M. A. Dessoy, J. De, E. M. Ethur, E. C. M. Dessoy, and A. F. Morel, “Heptakis(6-O-ethyl-2,3-O-pentyl)-β-cyclodextrin: a new chiral stationary phases for capillary GC,” HRC Journal of High Resolution Chromatography, vol. 22, no. 4, pp. 242–244, 1999.
View at: Google Scholar
AIST, Integrated Spectral Database System of Organic Compounds, National Institute of Advanced Industrial Science and Technology, Japan, 2011.
WSS: Spectral data were obtained from Wiley Subscription Services, Inc. USA.
J. Krupcik, E. Benicka, P. Majek, I. Skacani, and P. Sandra, “Relationship between structure and chromatographic behaviour of secondary alcohols and their derivatives separated by high-resolution gas chromatography with a modified β-cyclodextrin stationary phase,” Journal of Chromatography A, vol. 665, no. 1, pp. 175–184, 1994.
View at: Publisher Site | Google Scholar
A. M. Stalcup, K. H. Ekborg, M. P. Gasper, and D. W. Armstrong, “Enantiomeric separation of chiral components reported to be in coffee, tea, or cocoa,” Journal of Agricultural and Food Chemistry, vol. 41, no. 10, pp. 1684–1689, 1993.
View at: Google Scholar
C. Bicchi, A. D'Amato, V. Manzin, and P. Rubiolo, “Cyclodextrin derivatives in GC separation of racemic mixtures of volatiles—part 11. Some applications of cyclodextrin derivatives in GC enantioseparations of essential oil components,” Flavour and Fragrance Journal, vol. 12, no. 2, pp. 55–61, 1997.
View at: Publisher Site | Google Scholar
H. R. Kim, H. S. Oh, H. J. Park, J. N. Kim, D. J. Jeon, and E. K. Ryu, “A facile 1,2-acetoxychlorination reaction of olefins by using the N,N-dimethtylacetamide/hydrogen chloride/m-chloroperbenzoic acid (or oxone) system,” Synthetic Communications, vol. 28, no. 1, pp. 159–165, 1998.
View at: Google Scholar
W. Y. Li, H. L. Jin, and D. W. Armstrong, “2,6-Di-O-pentyl-3-O-trifluoroacetyl cyclodextrin liquid stationary phases for capillary gas chromatographic separation of enantiomers,” Journal of Chromatography, vol. 509, no. 2, pp. 303–324, 1990.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2012 Mireia Oromí-Farrús et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

5178

Downloads

1808

Citations