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 [ 13 ] . 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 [ 612 ] .
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 .
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 .
although different methods are described in the literature [ 1520 ] , 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 ) .
ramalinga and coworkers described iodine as a lewis catalyst for the esterification and transesterification of acids using an excess of alcohol under reflux conditions .
chavan and coworkers described the transesterification in toluene of -ketoesters with some primary , secondary alcohols and phenols using iodine as a catalyser in the presence of zinc as a mediator .
afterwards , they described that even iodine acts as an efficient catalysts for transesterification reactions ; however , phenols did not undergo transesterification .
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 .
recently , jereb and coworkers have demonstrated that iodine is an efficient catalyst for esterification under solvent - free conditions for several alcohols .
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 .
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 .
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 .
1-methylhexyl acetate was obtained by stirring at 100c 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 .
the organic solution was washed with saturated sodium thiosulfate solution , saturated nhco3 solution , and water .
hexane was stripped off by distillation at 69c at atmospheric temperature and the 1-methylhexyl acetate was obtained .
the product was characterized by nmr h and c. 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 140c ) for different reaction times ( 4 , 8 , 24 and 48  h ) in 3  ml amber screw - cap vials .
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 .   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 100c 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 .
( 1 ) no chiral - phase gc analysisgc - 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  m film thickness .
the gc temperature was programmed at 70c and ramped first at 5c / min to 160c and later at 10c / min to 200c . 
 
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  m film thickness .
the gc temperature was programmed at 70c and ramped first at 5c / min to 160c and later at 10c / min to 200c . 

( 2 ) chiral - phase gc analysisthe column used was cp chirasil - dex cb varian ( modified -cyclodextrins bonded to a dimethylpolysiloxane ) ( 25  m  0.25  mm diameter , 0.25  m film thickness ) .
the column used was cp chirasil - dex cb varian ( modified -cyclodextrins bonded to a dimethylpolysiloxane ) ( 25  m  0.25  mm diameter , 0.25  m film thickness ) .
h and c nmr spectra were recorded on a varian as400 spectrometer , operating at 400  mhz .
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 .
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 100c for 24 and 48 
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   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 .
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 ) .
we decided to carry out the subsequent reactions using a 1  :  1.5 molar ratio alcohol  :  acid at 100c 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 100c 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 [ 1520 ] .
moreover , any solvent was needed [ 28 , 29 ] , there were not any byproducts formation , and an equimolar amount of reactives can be used . 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 .
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 (  ) related to the free alcohols was determined . a resolution factor of 1.5 or greater indicates baseline enantiomeric resolution .  

the best  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 
higher  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 ) .
smith and simpson   investigated the separation of enantiomers of these acyclic alcohols on a -trifluoroacetylated cyclodextrin phase at 35c , showing for the majority of them an  value similar to or lower than those obtained in our -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 (  ,  ,  : on a -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 ,
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 .
they have already demonstrated that any isomerization was provoked in both compounds when acetylated separately .
the  value was higher than the  obtained in some  ,  , and  permethylated cyclodextrins [ 13 , 33 ] and in stationary gc phases of other cyclodextrin derivatives [ 3941 ] .   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 h and c spectra were in concordance with the chromatograms .
the acetylation of one hydroxyl group increased the  value , compared with their corresponding alcohols ; moreover , the  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  value ( 1.05 ) for the 1,2-octanediol on a -2,6-di - o - pentyl-3-o - trifluoroacetylated cyclodextrin but lower than the separation of mono- and diacetates in our column .
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 .
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 .
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 .
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 .


 1-ethylbutyl acetate 
 h nmr ( 400  mhz , acetone )  4.814.72 ( m , 1h ) , 1.99 ( s , 3h ) , 1.631.44 ( m , 4h ) , 1.411.22 ( m , 2h ) , 0.89 ( t , j = 7.47 , hz 3h ) , 0.85 ( t , j = 7.47  hz , 3h ) .
c nmr ( 101  mhz , acetone )  170.08 , 74.31 , 35.71 , 26.85 , 20.14 , 18.35 , 13.33 , 9.02 . 
 

h nmr ( 400  mhz , acetone )  4.814.72 ( m , 1h ) , 1.99 ( s , 3h ) , 1.631.44 ( m , 4h ) , 1.411.22 ( m , 2h ) , 0.89 ( t , j = 7.47 , hz 3h ) , 0.85 ( t , j = 7.47  hz , 3h ) .
c nmr ( 101  mhz , acetone )  170.08 , 74.31 , 35.71 , 26.85 , 20.14 , 18.35 , 13.33 , 9.02 . 


1-methylheptyl acetate 
 h nmr ( 400  mhz , acetone )  4.894.76 ( m , 1h ) , 1.96 ( s , 3h ) , 1.601.43 ( m , 2h ) , 1.28 ( m , 8h ) , 1.16 ( d , j = 6.27  hz , 3h ) , 0.88 ( t , j = 6.8  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.65 , 70.17 , 35.73 , 31.59 , 29.15 , 25.19 , 22.34 , 20.28 , 19.35 , 13.43 . 
 

h nmr ( 400  mhz , acetone )  4.894.76 ( m , 1h ) , 1.96 ( s , 3h ) , 1.601.43 ( m , 2h ) , 1.28 ( m , 8h ) , 1.16 ( d , j = 6.27  hz , 3h ) , 0.88 ( t , j = 6.8  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.65 , 70.17 , 35.73 , 31.59 , 29.15 , 25.19 , 22.34 , 20.28 , 19.35 , 13.43 . 


1-ethylhexyl acetate 
 h nmr ( 400  mhz , acetone )  4.76 ( dt , j = 7.2 , 6.2  hz , 1h ) , 1.98 ( s , 3h ) , 1.631.46 ( m , 4h ) , 1.371.21 ( m , 6h ) , 0.88 ( t , j = 7,46  hz , 3h ) , 0.86 ( t , j = 7 , 46  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.86 , 74.64 , 33.46 , 31.52 , 26.80 , 24.83 , 22.30 , 20.14 , 13.37 , 9.01 . 
 

h nmr ( 400  mhz , acetone )  4.76 ( dt , j = 7.2 , 6.2  hz , 1h ) , 1.98 ( s , 3h ) , 1.631.46 ( m , 4h ) , 1.371.21 ( m , 6h ) , 0.88 ( t , j = 7,46  hz , 3h ) , 0.86 ( t , j = 7 , 46  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.86 , 74.64 , 33.46 , 31.52 , 26.80 , 24.83 , 22.30 , 20.14 , 13.37 , 9.01 . 

cis-3-methylcyclopentyl acetate 
 h nmr ( 400  mhz , acetone )  3.90 ( m , 1h ) , 1.93 ( s , 3h ) , 1.98 ( m , 1h ) , 1.68 ( m , 1h ) , 1.591.49 ( m , 3h ) , 1.29 ( m , 1h ) , 1.16 ( m , 1h ) , 0.98 ( d , 3h ) .
c nmr ( 101  mhz , acetone )  169.70 , 76.14 , 41.16 , 32.76 , 32.36 , 32.30 , 20.27 ch3 , 20.24 . 
 

h nmr ( 400  mhz , acetone )  3.90 ( m , 1h ) , 1.93 ( s , 3h ) , 1.98 ( m , 1h ) , 1.68 ( m , 1h ) , 1.591.49 ( m , 3h ) , 1.29 ( m , 1h ) , 1.16 ( m , 1h ) , 0.98 ( d , 3h ) .
c nmr ( 101  mhz , acetone )  169.70 , 76.14 , 41.16 , 32.76 , 32.36 , 32.30 , 20.27 ch3 , 20.24 . 

trans-3-methylcyclopentyl acetate 
 h nmr ( 400  mhz , acetone )  5.07 ( m , 1h ) , 1.94 ( s , 3h ) , 1.831.72 ( m , 2h ) , 1.641.53 ( m , 2h ) , 1.431.30 ( m , 2h ) , 1.221.11 ( m , 1h ) , 1.02 ( dd , j = 5.3 , 4.0  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.75 , 76.16 , 40.78 , 32.84 , 32.38 , 32.33 , 20.11 , 19.52 . 
 

h nmr ( 400  mhz , acetone )  5.07 ( m , 1h ) , 1.94 ( s , 3h ) , 1.831.72 ( m , 2h ) , 1.641.53 ( m , 2h ) , 1.431.30 ( m , 2h ) , 1.221.11 ( m , 1h ) , 1.02 ( dd , j = 5.3 , 4.0  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.75 , 76.16 , 40.78 , 32.84 , 32.38 , 32.33 , 20.11 , 19.52 . 

trans-2-methylcyclopentyl acetate 
 h nmr ( 400  mhz , acetone )  4.62 ( dt , j = 6.8 , 4.6  hz , 1h ) , 1.96 ( m , 1h ) , 1.96 ( s , 3h ) , 1.711.61 ( m , 3h ) , 1.591.49 ( m , 2h ) , 1.20 ( m , 1h ) , 0.97 ( d , j = 6.9  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.94 , 82.07 , 39.86 , 31.56 , 31.04 , 22.06 , 20.21 , 17.53 . 
 

h nmr ( 400  mhz , acetone )  4.62 ( dt , j = 6.8 , 4.6  hz , 1h ) , 1.96 ( m , 1h ) , 1.96 ( s , 3h ) , 1.711.61 ( m , 3h ) , 1.591.49 ( m , 2h ) , 1.20 ( m , 1h ) , 0.97 ( d , j = 6.9  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.94 , 82.07 , 39.86 , 31.56 , 31.04 , 22.06 , 20.21 , 17.53 . 

cis-2-methylcyclopentyl acetate 
 h nmr ( 400  mhz , acetone )  4.81 ( m , 1h ) , 1.97 ( m , 1h ) , 1.97 ( s , 3h ) , 1.681.57 ( m , 3h ) , 1.531.43(m , 2h ) , 1.17 ( m , 1h ) , 0.96 ( d , j = 6.9  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.92 , 80.21 , 39.38 , 32.43 , 332.17 , 22.22 , 20.19 , 17.52 . 
 

h nmr ( 400  mhz , acetone )  4.81 ( m , 1h ) , 1.97 ( m , 1h ) , 1.97 ( s , 3h ) , 1.681.57 ( m , 3h ) , 1.531.43(m , 2h ) , 1.17 ( m , 1h ) , 0.96 ( d , j = 6.9  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.92 , 80.21 , 39.38 , 32.43 , 332.17 , 22.22 , 20.19 , 17.52 . 

cis-3-methylcyclopentyl acetate 
 h nmr ( 400  mhz , acetone )  4.98 ( m , 1h ) , 1.98 ( s , 3h ) , 1.931.86 ( m , 2h ) , 1.651.35 ( m , 2h ) , 1.301.13 ( m , 2h ) , 1.02 ( m , 1h ) , 0.86 ( d , j = 6.6  hz , 3h ) , 0.87 ( m , 2h ) .
c nmr ( 101  mhz , acetone )  169.44 , 69.51 , 38.12 , 33.89 , 31.20 , 30.51 , 26.87 , 21.54 , 20.40 . 
 

h nmr ( 400  mhz , acetone )  4.98 ( m , 1h ) , 1.98 ( s , 3h ) , 1.931.86 ( m , 2h ) , 1.651.35 ( m , 2h ) , 1.301.13 ( m , 2h ) , 1.02 ( m , 1h ) , 0.86 ( d , j = 6.6  hz , 3h ) , 0.87 ( m , 2h ) .
c nmr ( 101  mhz , acetone )  169.44 , 69.51 , 38.12 , 33.89 , 31.20 , 30.51 , 26.87 , 21.54 , 20.40 . 

trans-3-methylcyclopentyl acetate 
 h nmr ( 400  mhz , acetone )  4.61 ( tt , j = 11.3 , 4.3  hz , 1h ) , 1.94 ( m , 3h ) , 1.931.87 ( m , 2h ) , 1.681.12 ( m , 5h ) , 0.91 ( d , j = 6.6  hz , 3h ) , 0.89 ( m , 2h ) .
c nmr ( 101  mhz , acetone )  169.42 , 72.49 , 40.36 , 35.36 , 33.80 , 31.13 , 23.69 , 21.68 , 20.32 . 
 

h nmr ( 400  mhz , acetone )  4.61 ( tt , j = 11.3 , 4.3  hz , 1h ) , 1.94 ( m , 3h ) , 1.931.87 ( m , 2h ) , 1.681.12 ( m , 5h ) , 0.91 ( d , j = 6.6  hz , 3h ) , 0.89 ( m , 2h ) .
c nmr ( 101  mhz , acetone )  169.42 , 72.49 , 40.36 , 35.36 , 33.80 , 31.13 , 23.69 , 21.68 , 20.32 . 

trans-4-methylcyclohexyl acetate 
 h nmr ( 400  mhz , acetone )  4.57 ( tt , j = 11.2 , 4.4  hz , 1h ) , 1.94 ( s , 3h ) , 1.771.66 ( m , 2h ) , 1.451.24 ( m , 5h ) , 1.100.99 ( m , 2h ) , 0.88 ( d , j = 6.5  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.49 , 72.65 , 32.48 , 31.52 , 31.45 , 21.25 , 20.33 . 
 

h nmr ( 400  mhz , acetone )  4.57 ( tt , j = 11.2 , 4.4  hz , 1h ) , 1.94 ( s , 3h ) , 1.771.66 ( m , 2h ) , 1.451.24 ( m , 5h ) , 1.100.99 ( m , 2h ) , 0.88 ( d , j = 6.5  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.49 , 72.65 , 32.48 , 31.52 , 31.45 , 21.25 , 20.33 . 

cis-4-methylcyclohexyl acetate 
 h nmr ( 400  mhz , acetone )  4.89 ( s , 1h ) , 1.98 ( s , 3h ) , 1.921.84 ( m , 2h ) , 1.821.68 ( m , 2h ) , 1.52 ( m , 3h ) , 0.95 ( m , 2h ) , 0.90 ( d , j = 6.4  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.45 , 69.01 , 32.22 , 31.52 , 31.14 , 21.25 , 21.45 . 
 

h nmr ( 400  mhz , acetone )  4.89 ( s , 1h ) , 1.98 ( s , 3h ) , 1.921.84 ( m , 2h ) , 1.821.68 ( m , 2h ) , 1.52 ( m , 3h ) , 0.95 ( m , 2h ) , 0.90 ( d , j = 6.4  hz , 3h ) .
c nmr ( 101  mhz , acetone )  169.45 , 69.01 , 32.22 , 31.52 , 31.14 , 21.25 , 21.45 . 

cis-4-tert - butylcyclohexyl acetate 
 h nmr ( 400  mhz , acetone )  4.55 ( m , 1h ) , 1.94 ( s , 3h ) , 1.81 ( m , 2h ) , 1.360.98 ( m , 7h ) , 0.86 ( s , 9h ) .
c nmr ( 101  mhz , acetone )  169.48 , 72.97 , 68.63 , 47.03 , 36.06 , 31.95 , 27.00 , 20.32 . 
 

h nmr ( 400  mhz , acetone )  4.55 ( m , 1h ) , 1.94 ( s , 3h ) , 1.81 ( m , 2h ) , 1.360.98 ( m , 7h ) , 0.86 ( s , 9h ) .
c nmr ( 101  mhz , acetone )  169.48 , 72.97 , 68.63 , 47.03 , 36.06 , 31.95 , 27.00 , 20.32 . 

trans-4-tert - butylcyclohexyl acetate 
 h nmr ( 400  mhz , acetone )  4.92 ( m , 1h ) , 1.99 ( s , 3h ) , 1.89 ( m , 4h ) , 1.541.40 ( m , 2h ) , 1.200.98 ( m , 3h ) , 0.86 ( s , 9h ) .
c nmr ( 101  mhz , acetone )  169.45 , 72.97 , 69.95 , 47.42 , 36.01 , 31.89 , 26.86 , 20.82 . 
 

h nmr ( 400  mhz , acetone )  4.92 ( m , 1h ) , 1.99 ( s , 3h ) , 1.89 ( m , 4h ) , 1.541.40 ( m , 2h ) , 1.200.98 ( m , 3h ) , 0.86 ( s , 9h ) .
c nmr ( 101  mhz , acetone )  169.45 , 72.97 , 69.95 , 47.42 , 36.01 , 31.89 , 26.86 , 20.82 . 

cis-3,3,5-trimethylcyclohexyl acetate 
 h nmr ( 400  mhz , acetone )  4.83 ( tt , j = 11.6 , 4.4  hz , 1h ) , 1.94 ( s , 3h ) , 1.931.89 ( m , 1h ) , 1.781.62 ( m , 1h ) , 1.35 ( ddt , j = 13.1 , 3.8 , 2.0  hz , 2h ) , 1.08 ( m , 2h ) , 0.94 ( s , 6h ) , 0.90 ( d , j = 6.5  hz , 3h ) , 0.960.78 ( m , 1h ) .
c nmr ( 101  mhz , acetone )  169.60 , 70.21 , 47.23 , 43.82 , 40.25 , 32.45 , 31.79 , 26.91 , 24.88 , 21.74 , 20.37 . 
 

h nmr ( 400  mhz , acetone )  4.83 ( tt , j = 11.6 , 4.4  hz , 1h ) , 1.94 ( s , 3h ) , 1.931.89 ( m , 1h ) , 1.781.62 ( m , 1h ) , 1.35 ( ddt , j = 13.1 , 3.8 , 2.0  hz , 2h ) , 1.08 ( m , 2h ) , 0.94 ( s , 6h ) , 0.90 ( d , j = 6.5  hz , 3h ) , 0.960.78 ( m , 1h ) .
c nmr ( 101  mhz , acetone )  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 
 h nmr ( 400  mhz , acetone )  5.02 ( s , 1h ) , 1.96 ( s , 3h ) , 1.90 ( m , 1h ) , 1.781.61 ( m , 2h ) , 1.471.39 ( m , 1h ) , 1.060.77 ( m , 3h ) , 0.89 ( d , j = 6.5  hz , 3h ) , 0.88 ( s , 6h ) .
c nmr ( 101  mhz , acetone )  169.34 , 70.17 , 47.81 , 40.87 , 38.08 , 33.38 , 30.26 , 26.76 , 23.22 , 21.93 , 20.49 . 
 

h nmr ( 400  mhz , acetone )  5.02 ( s , 1h ) , 1.96 ( s , 3h ) , 1.90 ( m , 1h ) , 1.781.61 ( m , 2h ) , 1.471.39 ( m , 1h ) , 1.060.77 ( m , 3h ) , 0.89 ( d , j = 6.5  hz , 3h ) , 0.88 ( s , 6h ) .
c nmr ( 101  mhz , acetone )  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 
 h nmr ( 400  mhz , acetone )  4.013.88 ( m , 2h ) , 3.43 ( m , 1h ) , 2.00 ( s , 3h ) , 1.521.18 ( m , 10h ) , 0.88 ( t , j = 7.16  hz 3h ) .
c nmr ( 101  mhz , acetone )  170.12 , 71.14 , 69.12 , 33.56 , 31.68 , 29.16 , 25.08 , 22.35 , 19.88 , 13.44 . 
 

h nmr ( 400  mhz , acetone )  4.013.88 ( m , 2h ) , 3.43 ( m , 1h ) , 2.00 ( s , 3h ) , 1.521.18 ( m , 10h ) , 0.88 ( t , j = 7.16  hz 3h ) .
c nmr ( 101  mhz , acetone )  170.12 , 71.14 , 69.12 , 33.56 , 31.68 , 29.16 , 25.08 , 22.35 , 19.88 , 13.44 . 


1-(hydroxymethyl)heptyl acetate 
 h nmr ( 400  mhz , acetone )  4.85 ( m , 1h ) , 3.55 ( m , 2h ) , 1.99 ( s , 3h ) , 1.651.20 ( m , 10h ) , 0.88 ( t , j = 7.16  hz 3h ) .
c nmr ( 101  mhz , acetone )  169.90 , 75.81 , 68.34 , 31.56 , 30.47 , 29.03 , 25.63 , 22.38 , 20.20 , 13.45 . 
 

h nmr ( 400  mhz , acetone )  4.85 ( m , 1h ) , 3.55 ( m , 2h ) , 1.99 ( s , 3h ) , 1.651.20 ( m , 10h ) , 0.88 ( t , j = 7.16  hz 3h ) .
c nmr ( 101  mhz , acetone )  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 
 h nmr ( 400  mhz , acetone )  5.01(m , 1h ) , 4.21 ( dd , j = 11.9 , 3.4  hz , 1h ) , 4.5 - 3,93 ( m , 1h ) , 1.99 ( s , 3h ) , 1.98 ( s , 3h ) , 1.651.20 ( m , 10 h ) , 0.88 ( t , j = 7.16  hz 3h ) .
c nmr ( 101  mhz , acetone )  169.98 , 169.79 , 74.67 , 68.66 , 31.62 , 30.40 , 28.84 , 24.90 , 22.31 , 20.03 , 19.73 , 13.41 . 
 

h nmr ( 400  mhz , acetone )  5.01(m , 1h ) , 4.21 ( dd , j = 11.9 , 3.4  hz , 1h ) , 4.5 - 3,93 ( m , 1h ) , 1.99 ( s , 3h ) , 1.98 ( s , 3h ) , 1.651.20 ( m , 10 h ) , 0.88 ( t , j = 7.16  hz 3h ) .
c nmr ( 101  mhz , acetone )  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 
 h nmr ( 400  mhz , acetone )  4.82 ( dd , j = 7.1 , 4.0  hz , 1h ) , 4.37 ( s , oh ) , 4.04 ( m , 1h ) , 1.99 ( s , 3h ) , 1.82 ( m , 1h ) , 1.771.61 ( m , 4h ) , 1.31 ( m , 2h ) , 1.411.21 ( m , 1h ) .
c nmr ( 101  mhz , acetone )  169.76 , 73.31 , 67.99 , 29.54 , 28.08 , 21.90 , 21.15 , 20.62 . 
 

h nmr ( 400  mhz , acetone )  4.82 ( dd , j = 7.1 , 4.0  hz , 1h ) , 4.37 ( s , oh ) , 4.04 ( m , 1h ) , 1.99 ( s , 3h ) , 1.82 ( m , 1h ) , 1.771.61 ( m , 4h ) , 1.31 ( m , 2h ) , 1.411.21 ( m , 1h ) .
c nmr ( 101  mhz , acetone )  169.76 , 73.31 , 67.99 , 29.54 , 28.08 , 21.90 , 21.15 , 20.62 . 

cis-2-(acetyloxy)cyclohexyl acetate 
 h nmr ( 400  mhz , acetone )  4.96 ( d , j = 8.4  hz , 2h ) , 1.97 ( s , 6h ) , 1.80 ( m , 2h ) , 1.691.59 ( m , 2h ) , 1.531.40 ( m , 4h ) .
c nmr ( 101  mhz , acetone )  169.49 , 73.78 , 29.54 , 27.30 , 20.09 . 
 

h nmr ( 400  mhz , acetone )  4.96 ( d , j = 8.4  hz , 2h ) , 1.97 ( s , 6h ) , 1.80 ( m , 2h ) , 1.691.59 ( m , 2h ) , 1.531.40 ( m , 4h ) .
c nmr ( 101  mhz , acetone )  169.49 , 73.78 , 29.54 , 27.30 , 20.09 . 

trans-2-hydroxycyclohexyl acetate 
 h nmr ( 400  mhz , acetone )  4.53 ( d , j = 8.9  hz , 1h ) , 3.49 ( m , 1h ) , 3.30 ( s , oh ) , 1.97 ( s , 3h ) , 1.91 ( m , 2h ) , 1.761.59 ( m , 2h ) , 1.391.16 ( m , 4h ) .
c nmr ( 101  mhz , acetone )  169.45 , 77.15 , 71.09 , 32.88 , 23.60 , 3.04 , 20.09 , 19.64 . 
 

h nmr ( 400  mhz , acetone )  4.53 ( d , j = 8.9  hz , 1h ) , 3.49 ( m , 1h ) , 3.30 ( s , oh ) , 1.97 ( s , 3h ) , 1.91 ( m , 2h ) , 1.761.59 ( m , 2h ) , 1.391.16 ( m , 4h ) .
c nmr ( 101  mhz , acetone )  169.45 , 77.15 , 71.09 , 32.88 , 23.60 , 3.04 , 20.09 , 19.64 . 

trans-2-(acetyloxy)cyclohexyl acetate 
 h nmr ( 400  mhz , acetone )  4.72 ( m , 2h ) , 1.95 ( s , 6h ) , 1.92 ( m , 2h ) , 1.64 ( m , 2h ) , 1.2431.23(m , 4h ) .
c nmr ( 101  mhz , acetone )  169.97 , 73.05 , 29.66 , 23.44 , 20.10 . 
 

h nmr ( 400  mhz , acetone )  4.72 ( m , 2h ) , 1.95 ( s , 6h ) , 1.92 ( m , 2h ) , 1.64 ( m , 2h ) , 1.2431.23(m , 4h ) .
c nmr ( 101  mhz , acetone )  169.97 , 73.05 , 29.66 , 23.44 , 20.10 . 

cis-3-hydroxycyclohexyl acetate 
 h nmr ( 400  mhz , acetone )  4.62 ( m , 1h ) , 3.57 ( m , 1h ) , 4.86 ( s , oh ) , 1.95 ( s , 3h ) , 1.931.77 ( m , 1h ) , 1.771.61 ( m , 1h ) , 1.611.46 ( m , 2h ) , 1.451.31 ( m , 3h ) , 1.311.06 ( m , 1h ) .
c nmr ( 101  mhz , acetone )  169.34 , 70.89 , 65.75 , 38.70 , 36.92 , 30.27 , 20.21 , 18.86 . 
 

h nmr ( 400  mhz , acetone )  4.62 ( m , 1h ) , 3.57 ( m , 1h ) , 4.86 ( s , oh ) , 1.95 ( s , 3h ) , 1.931.77 ( m , 1h ) , 1.771.61 ( m , 1h ) , 1.611.46 ( m , 2h ) , 1.451.31 ( m , 3h ) , 1.311.06 ( m , 1h ) .
c nmr ( 101  mhz , acetone )  169.34 , 70.89 , 65.75 , 38.70 , 36.92 , 30.27 , 20.21 , 18.86 . 

trans-3-hydroxycyclohexyl acetate 
 h nmr ( 400  mhz , acetone )  5.01 ( m , 1h ) , 3.96 ( m , 1h ) , 4.86 ( s , oh ) , 1.98 ( s , 3h ) , 1.931.77 ( m , 1h ) , 1.771.61 ( m , 1h ) , 1.611.46 ( m , 2h ) , 1.451.31 ( m , 3h ) , 1.311.06 ( m , 1h ) .
c nmr ( 101  mhz , acetone )  169.43 c , 69.93 , 65.58 , 41.29 , 35.20 , 29.82 , 20.29 , 19.00 . 
 

h nmr ( 400  mhz , acetone )  5.01 ( m , 1h ) , 3.96 ( m , 1h ) , 4.86 ( s , oh ) , 1.98 ( s , 3h ) , 1.931.77 ( m , 1h ) , 1.771.61 ( m , 1h ) , 1.611.46 ( m , 2h ) , 1.451.31 ( m , 3h ) , 1.311.06 ( m , 1h ) .
c nmr ( 101  mhz , acetone )  169.43 c , 69.93 , 65.58 , 41.29 , 35.20 , 29.82 , 20.29 , 19.00 . 

cis-3-(acetyloxy)cyclohexyl acetate 
 h nmr ( 400  mhz , acetone )  4.69 ( m , 2h ) , 1.96 ( s , 6h ) , 1.941.78 ( m , 3h ) , 1.781.61 ( m , 1h ) , 1.611.31 ( m , 2h ) , 1.311.07 ( m , 2h ) .
c nmr ( 101  mhz , acetone )  171.09 , 70.05 , 34.50 , 30.87 , 20.38 , 19.78 . 
 

h nmr ( 400  mhz , acetone )  4.69 ( m , 2h ) , 1.96 ( s , 6h ) , 1.941.78 ( m , 3h ) , 1.781.61 ( m , 1h ) , 1.611.31 ( m , 2h ) , 1.311.07 ( m , 2h ) .
c nmr ( 101  mhz , acetone )  171.09 , 70.05 , 34.50 , 30.87 , 20.38 , 19.78 .  

trans-3-(acetyloxy)cyclohexyl acetate 
 h nmr ( 400  mhz , acetone )  5.06 ( m , 2h ) , 1.96 ( s , 6h ) , 1.941.78 ( m , 3h ) , 1.781.61 ( m , 1h ) , 1.611.31 ( m , 2h ) , 1.311.07 ( m , 2h ) .
c nmr ( 101  mhz , acetone )  171.09 , 69.45 , 34.57 , 30.47 , 20.33 , 19.58 . 
 

h nmr ( 400  mhz , acetone )  5.06 ( m , 2h ) , 1.96 ( s , 6h ) , 1.941.78 ( m , 3h ) , 1.781.61 ( m , 1h ) , 1.611.31 ( m , 2h ) , 1.311.07 ( m , 2h ) .
c nmr ( 101  mhz , acetone )  171.09 , 69.45 , 34.57 , 30.47 , 20.33 , 19.58 .
 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 (  = 3.00 ) and 2-hexyl acetates (  = 1.95 ) . 
 this method provides a very simple and efficient experimental workup procedure for analyzing chiral alcohols by chiral - phase gc . 