Y. J. K. Araujo et al. / Tetrahedron Letters 56 (2015) 1696–1698
1697
Scheme 1. Preparation of epichlorohydrin from glycerol and production of esters.
For synthesis of the desired esters, we replaced the chlorine
atom of epichlorohydrin (4± by selected carboꢀylate groups
Scheme 1±. Epichlorohydrin (4± was prepared by bubbling gaseous
and dried HCl in a heated miꢀture (105–110 °C± of glycerol (5± with
in an eꢀcellent yield for the sodium salt, but only moderate for potas)
sium salt. This difference of reactivity is likely due to the slightly
higher solubility of sodium salt in organic solvents. The aggregation
of the ionic pair/compleꢀ reduces the reactivity by reducing the
effective concentration of the nucleophile in the organic phase.1
The benzoates reactivity was similar in both polar and nonpolar
solvents, leading to moderate yields after 5 h reaction. The ben)
zoates and butyrates are close in solubility, but are less reactive
since its nucleophilicity is attenuated by electronic delocalization
effect of the aromatic ring.
(
7,18
catalytic amount of acetic acid, followed by dehydro)chlorination
1
2
with NaOH pellets leading to moderate yields of the desired pro)
duct (ꢀ60%±.
Carboꢀylates of sodium or potassium are not very reactive
nucleophiles. However, using the phase)transfer catalysis system
(
ly.
PTC±, the rate of this type of reaction can be increased drastical)
1
3–15
The method induces or accelerates the reaction between
The great stereoselectivity of lipases make them very important
catalysts in organic chemistry. Even used as a single type of
enzyme, they can recognize different substrates promoting many
type of reactions such as the preparation of enantiomerically pure
compounds that are either solubilized or form different phases by
14
the action of a transfer agent or catalyst. Thus, sodium and potas)
sium acetate, butyrate and benzoate where submitted to reaction
1
9
with epichlorohydrin in the presence of suitable crown ethers as
compounds.
phase)transfer catalyst in a solid–liquid system.1
5,16
It was chosen
In the present study we focused our attention to lipase Ther-
momyces lanuginosa (TLL± and Candida rugosa (CRL±. TLL is ther)
mostable, commercially available in solution or immobilized. It is
widely used in the food and fine chemical industries as well as
1
7
toluene and acetonitrile to evaluate the effect of solvent polarity.
However, in the tested conditions the yields were very low (<3%±.
Take in account that tetra)n)butylammonium bromide (TBAB± has
been used as a catalyst in allylation of sodium phenoꢀide in a
1
9
for the production of biodiesel. Despite the great potential of
TLL in chemical process, we could not find any report in the lit)
erature of its use in kinetic resolution of 2,3)epoꢀy propyl esters.
1
6
solid–liquid system, we decided to make use of it in place of
crown ethers (Scheme 1± and, the results are presented in Table 1.
With respect to ester 6 the best results were obtained when ace)
tonitrile was used as solvent (20% and 45% for sodium and potassi)
um salts, respectively±, while in toluene, the yields were very poor
8
Nair et al. observed the enantioselective hydrolysis of various
(± ±)2,3)epoꢀy propyl esters catalyzed by lipase from Pseudomonas
cepacia (PS)C ‘Amano’ II±, and their kinetic resolution were selec)
tive for aromatic esters, however, lipase PS)C was not capable of
catalyzing the aliphatic esters hydrolysis (acetate, butyrate and
propionate±. Nevertheless, in our work, (± ±)glycidyl butyrate 7
was obtained in a good enantiomeric eꢀcess of (R±)ester (99%±
when phosphate buffer was used as solvent and 1,4)dioꢀane as
co)solvent in the presence of lipase from Thermomyces lanuginosa
(Scheme 2 and Table 2±. Similar results were obtained by Li et al.20
using lipase from Bacillus subtilis (BSL2± where the authors report)
ed an ee >98% of (R±)butyrate when the conversion was above 52%.
(
10% and 15%, respectively±. The reaction in toluene produced a
good yield (90%± of ester 7, especially in the presence of sodium
butyrate (70% when used potassium butyrate±. As for the benzoate
8
, no significant differences in yields were observed (ꢀ60%± using
either toluene or acetonitrile. All the eꢀperiments were dealt under
triplicate basis and, it was observed that the reactions are not suc)
cessful without the catalyst.
The acetate salts present low solubility in both used solvents;
however they are more soluble in the more polar solvent acetoni)
trile, resulting in acceleration of the reaction and higher yields. On
the other hand, carboꢀylate ions of longer carbon chain, as the buty)
rate, are more soluble in the hydrophobic solvent toluene, reflecting
Table 1
Preparation of (± ±)2,3)epoꢀy propyl esters using TBAB as a phase transfer catalyst in
toluene and acetonitrile
Salt
Solventa
Product
Time (h±
Yield (%±
Scheme 2. Enzymatic resolution by hydrolysis of (± ±)glycidyl esters.
CH
3
CO
2
2
Na
K
MeCN
Toluene
MeCN
6
5
5
5
5
20
10
45
15
CH
3
CO
Table 2
Toluene
Kinetic resolution of 7 and 8 by lipases from Thermomyces lanuginosa and Candida
rugosa, respectively
CH
3
3
(CH
2
±
2
2
CO
2
2
Na
K
MeCN
Toluene
MeCN
7
8
5
5
5
5
35
90
30
70
*
CH
(CH
2
±
CO
Compound
Lipase from
Temp (°C±
Time (h±
ees (%±
Toluene
>99a (R±
7
7
8
T. lanuginosa
T. lanuginosa
C. rugosa
30
50
30
2
2
6
a
C
C
6
H
H
5
CO
CO
2
Na
MeCN
Toluene
MeCN
5
5
5
5
60
60
65
60
>99 (R±
b
34 (R±
6
5
2
K
a
b
*
Determined by GC (Chiraldeꢀ B)PM Column±.
Determined by HPLC (Chiraldeꢀ G)TA column±.
ees = substrate enantiomeric eꢀcess.
Toluene
a
Anhydrous, at refluꢀ.