Facile synthesis of glycidates via oxidation of acrylates with aqueous solution of naocl in the presence of ammonium salts

Article abstract of DOI:10.3987/COM-13-12895

Various glycidates were obtained in high yields via green oxidation of acrylates with aqueous solution of NaOCl in the presence of ammonium salts. The appropriate choice of ammonium salts fitting to the polarity of the substrates and the reaction under slightly basic conditions were essential for efficient reactions.

Full text of DOI:10.3987/COM-13-12895

HETEROCYCLES, Vol. 89, No. 2, 2014
487
HETEROCYCLES, Vol. 89, No. 2, 2014, pp. 487 - 493. © 2014 The Japan Institute of Heterocyclic Chemistry
Received, 21st November, 2013, Accepted, 20th December, 2013, Published online, 25th December, 2013
DOI: 10.3987/COM-13-12895
FACILE SYNTHESIS OF GLYCIDATES VIA OXIDATION OF
ACRYLATES WITH AQUEOUS SOLUTION OF NaOCl IN THE
PRESENCE OF AMMONIUM SALTS
*
Bungo Ochiai and Taiki Hirano
Department of Chemistry and Chemical Engineering, Faculty of Engineering,
Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510; E-mail:
ochiai@yz.yamagata-u.ac.jp
Abstract – Various glycidates were obtained in high yields via green oxidation of
acrylates with aqueous solution of NaOCl in the presence of ammonium salts. The
appropriate choice of ammonium salts fitting to the polarity of the substrates and
the reaction under slightly basic conditions were essential for efficient reactions.
Facile synthesis of epoxides with easily accessible reagents is a very important subject due to the high
1
,2
3
importance of epoxides both as intermediates and reactive materials. A typical method for preparing
3
,4-16
epoxides is oxidation of C=C double bond moieties.
However, only a few effort has been conducted
for efficient oxidation of acrylates yielding epoxides bearing ester moieties (glycidates) in spite of their
wide variety of the commercial products. Glycidates are interesting building blocks for various
5
-7,9,17
pharmaceutical and biologically active compounds.
Typical oxidants employed for this oxidation are
5
-10
11
12,13
14
15
NaOCl,
dimethyldioxirane, t-BuOOH with BuLi,
and H O with hetero-polyacid or Mn
2 2
1
6
catalysts and NaHCO as the activator. The yields attained by references 14 and 15 were quantitative,
3
but the reagents used are not easily accessible. NaOCl is advantageous in price and accessibility. The
oxidation without catalysts resulted in moderate yields, but a patent literature reported that use of
methyltrioctylammonium chloride (Oct MeNCl) as a phase transfer catalyst significantly improved the
3
yields of the synthesis of n-butyl (BG) and ethyl glycidates from n-butyl (BA) and ethyl (EA) acrylates to
1
0
9
4 and 86%, respectively. We presume that the ammonium salts probably exchange the anion with
-
-
NaOCl to obtain OCl in place of Cl , and served as amphiphilic oxidation species. Although oxidation of
other !,"-unsaturated esters such as crotonates was also reported, oxidation of other acrylates was not
disclosed. This oxidation was conducted in the mixture of NaOCl aqueous solution and ethyl acetate, and
took relatively long time (e.g., 4 hours of dropwise addition of NaOCl solution and additional 3 hours of

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HETEROCYCLES, Vol. 89, No. 2, 2014
stirring). Accordingly, we examined the oxidation of various acrylates and optimized the conditions to
obtain various glycidates in high yields.
First, the reaction conditions were optimized employing BA at 40 ˚C in 1 h in a similar manner with the
patent literature (Scheme 1). The effect of organic solvent was examined using Bu NCl (32 mol%) and
4
NaHCO aqueous solution (pH = 8.2) (Table 1). We used a commercial 5wt% aqueous solution of NaOCl
3
(
[NaOCl] /[BA] = 1.2). As a result, the best result was obtained without the use of organic solvents
0 0
regardless of the polarity or the water-miscibility. Hydrolysis to produce a diol was responsible to the
8
difference between the conversion of BA and the formation of BG. Longer time did not increase the
conversion, but led to hydrolysis of the resulting epoxide. This result implies that additional organic
solvents and longer times are not necessary in this case. Pure BG could be isolated by washing with brine
after adding EtOAc followed by distillation or SiO column chromatography.
2
Scheme 1
Table 1. Effect of organic solvents on oxidation of BA with NaOCl aq. in the presence of Bu NCl.
4
a
a
Run
1
Solvent
none
Conv. of BA /%
Formation of BG /%
87
88
66
85
85
79
55
73
2
MeCN
DMF
3
4
EtOAc
Conditions: 40 °C, 1 h, [BA] /[NaOCl] /[Bu NCl] = 1/1.2/0.3, BA = 40 mmol, NaHCO aq. (pH = 8.2) =
0
0
4
3
7
.18 g, 5wt% NaOCl = 65.4 mL. Solvent = 60 mL.
a
1
Determined by H NMR spectroscopy (400 MHz, CDCl ).
3
Next, the effect of pH was investigated using various aqueous solutions with pH values adjusted by
NaHCO and acetic acid (Table 2). The conversions of BA and the formation of BG were identical under
3
basic conditions. The conversions decreased under acidic conditions probably because decomposition of
NaOCl by acetic acid. The slightly basic solution with the pH value of 8.2 resulted in the highest
formation of BG owing to the suppression of hydrolysis of epoxide moieties (run 5). We accordingly used
the aqueous solution of NaHCO with the pH value of 8.2.
3

HETEROCYCLES, Vol. 89, No. 2, 2014
489
The effect of the halide was also investigated (Table 3). The reaction without catalysts was also
6
,8
conducted as a reference, and resulted in a very unsuccessful result as reported. Both the conversions
and the formations were in the order of Bu NCl > Bu NBr > Bu NI. This result supports our presumption
4
4
4
that the actual oxidation species are ammonium hypochlorites produced in situ via anionic exchange with
NaOCl in a similar manner with the anion exchange between KOCl and an ammonium salt for
1
8
enantioselective epoxidation of enones. Sodium halides are produced by this anion exchange that should
+
-
-
-
proceed smoothly in the order of the affinity of the anions with Na , namely Cl > Br > I .
Table 2. Effect of pH on oxidation of BA with NaOCl aq. in the presence of Bu NCl.
4
a
a
Run
1
pH
3.7
Conv. of BA /%
Formation of BG /%
77
78
85
85
87
84
86
88
71
73
79
74
85
76
75
76
2
5.0
3
6.2
4
7.7
5
8.2
6
9.5
7
10.6
11.7
8
Conditions: 40 °C, 1 h, [BA] /[NaOCl] /[Bu NCl] = 1/1.2/0.3, BA = 40 mmol, aqueous solutions = 7.18 g,
0
0
4
5
wt% NaOCl = 65.4 mL.
a
1
Determined by H NMR spectroscopy (400 MHz, CDCl ).
3
Table 3. Effect of halide on oxidation of BA with NaOCl aq. in the presence of Bu NX
4
a
a
Run
1
Catalyst
none
Conv. of BA /%
Formation of BG /%
15
87
72
17
13
85
57
15
2
Bu NCl
4
3
Bu NBr
4
4
Bu NI
4
Conditions: 40 °C, 1 h, [BA] /[NaOCl] /[Bu NX] = 1/1.2/0.3, BA = 40 mmol, NaHCO aq. (pH = 8.2) =
0
0
4
3
7
.18 g, 5wt% NaOCl = 65.4 mL.
a
1
Determined by H NMR spectroscopy (400 MHz, CDCl ).
3
Under the optimized conditions, epoxidation of various alkyl acrylates were examined using various
tetraalkylammonium chlorides (Figure 1). Catalysts with alkyl chains similar to substrates tended to gave

490
HETEROCYCLES, Vol. 89, No. 2, 2014
1
0
higher yields. Oct MeNCl, reported in the patent, was most suitable for quantitative formation of
3
glycidates with long alkyl chains (92, 94, and 92% for n-Bu, 2-ethylhexyl, and n-dodecyl glycidates,
respectively), but was not for the methyl (58%) and ethyl (69%) analogues. The decrease of the yield in
the reaction of EA from the patent literature is attributable to the absence of EtOAc allowing the
interaction between the oxidation species with the very low polarity and EA with the relatively high
polarity.
Figure 1. Synthesis of glycidates by oxidation of acrylates with NaOCl in the presence of various
ammonium salts
Use of Bu NCl having shorter alkyl chains was effective to the reactions of these acrylates with lower
4
hydrophobicity, and the yields (82% and 80% for methyl and ethyl glycidate, respectively) were
comparable to that reported in the patent. Cost effective Bu NCl is advantageous over Oct MeNCl.
4
3
Catalysts with shorter chains were useless for the reactions of acrylates with long alkyl chains due to the
very low ability as phase transfer catalysts. The highest yields for the examined substrates were
comparable to those in the previous patent, and this reaction system is advantageous by the elimination of
EtOAc from the reaction system and the significantly shortened reaction time.
In conclusion, various glycidates could be obtained via a facile and fast oxidation of acrylates by NaOCl
aq. under ambient conditions. The use of ammonium catalysts with appropriate structures and the reaction
under slightly basic conditions were important for selective reactions. The improvements from previous
works are the shorter reaction time, the simpler procedure, and the cost effectiveness of the catalyst for
methyl and ethyl glycidates. The organic solvent free reaction is also a potential advantage, and we are

HETEROCYCLES, Vol. 89, No. 2, 2014
491
now trying to construct the reaction system excluding any organic solvents from the total synthetic
process by optimizing the purification process. Investigations on the reactions of the glycidates are also
ongoing.
EXPERIMENTAL
Materials. NaOCl was purchased as 5-wt% aqueous solution (Kanto Chemical, Tokyo, Japan). Water
was distilled using a STILL ACE SA-2100A water distillation instrument (EYELA, Tokyo, Japan) prior
to use. Other reagents were used as received.
1
13
Instruments. H (400 MHz) and C (100 MHz) nuclear magnetic resonance (NMR) spectra were
measured on a JEOL ECX-400 instrument using tetramethylsilane as an internal standard. Resolved
1
H-NMR spectra could be obtained using DMSO-d as a solvent, whereas the spectra obtained using
6
CDCl showed overlaps of signals. Fourier transform infrared (FT-IR) spectra were measured on a
3
JASCO FT/IR-470 Plus instrument. Elemental analysis was performed on a Perkin Elmer CHNS/O2400II
analyzer.
Typical reaction procedure: synthesis of 2-ethylhexyl glycidate
MeOct NCl (3.23 g, 40 mmol) and 2-ethylhexyl acrylate (EHA) (7.37 g, 400 mmol) were added to a test
3
tube. Then, 5 wt-% NaOCl aq. (65.4 mL) and a buffer solution (7.18 g, 78 g/L) with pH (8.2) adjusted by
1
NaHCO were added. The solution was stirred for 1 h at 40 ˚C. The contents were analyzed by H NMR
3
spectroscopy to determine the conversion of the acrylate and the formation of the product. EtOAc (50
mL) and brine (50 mL) were added to the reaction mixture, and the separated organic layer was washed
three times with brine (50 mL). The organic layer was dried with MgSO . After volatile substances were
4
evaporated off, the product was purified by silica gel column chromatography (7.68 g, 387 mmol,
9
6.8%).
1
H NMR (DMSO-d , 400 MHz, ! in ppm): 4.18–4.05 (m, 2H, -COOCH -), 3.53 (dd, 2H, J = 3.2 and 3.6
6
2
Hz, -OCHCOO-), 2.91 (dd, 1H, J = 3.6 and 6.4 Hz, -OCH CHCOO-), 2.83 (dd, 1H, J = 3.2 and 6.4 Hz,
2
-
OCH CHCOO-), 1.60–1.50 (m, 1H, CH CH CH<), 1.35–1.24 (m, 2H, -CH(CH CH )(CH ) -), 0.87 (t,
2 3 2 2 3 2 3
1
3
3
H, J = 6.8 Hz, -CH(CH CH )), 0.86 (t, 3H, J = 7.6 Hz, -(CH ) CH ). C NMR (CDCl , 100 MHz, ! in
2 3 2 3 3 3
ppm): 169.4 (>C=O), 67.8 (-COOCH -), 47.3 (-CHCH - in epoxy ring), 46.2 (-CHCH - in epoxy ring),
2
2
2
3
8.6 (CH CH CH<), 30.2 (CH CH CH CH -), 28.8 (CH CH CH -), 23.6 (CH CH CH<), 22.9 (CH CH-
3 2 3 2 2 2 3 2 2 3 2 3
CH -), 14.0 (CH (CH ) -), 10.9 (CH CH CH<). Anal. Calcd for C H O : C 65.97; H 10.07. Found: C
2
2
3
2 3
3
2
11 20
3
6
5.95; H 10.10.
Spectroscopic data of other novel compounds.
1
n-Hexyl glycidate. H NMR (CDCl , 400 MHz, ! in ppm): 4.09 (t, 2H, J = 6.8 Hz, -COOCH -), 3.52 (dd,
3
2
1
H, J = 3.7 and 3.6 Hz, -CH-), 2.94 (dd, 1H, J = 3.6 and 6.0 Hz, -OCH CHCOO-), 2.82 (dd, 1H, J = 3.6
2

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HETEROCYCLES, Vol. 89, No. 2, 2014
and 6.4 Hz, -OCH CHCOO-), 1.80–1.60 (m, 2H, -COOCH CH -), 1.40–1.25 (m, 6H, -(CH ) CH ), 0.85 (t,
2
2
2
2 3
3
1
3
3
H, J = 7.0 Hz, -CH ). C NMR (CDCl , 100 MHz, ! in ppm): 169.3 (>C=O), 66.5 (-COOCH -), 47.3
3 3 2
(
-CHCH - in epoxy ring), 46.2 (-CHCH - in epoxy ring), 31.4 (-COOCH CH -), 28.4 (CH CH CH CH -),
2 2 2 2 3 2 2 2
2
5.4 (CH CH CH -), 22.4 (CH CH -), 13.9 (CH -). Anal. Calcd for C H O : C 62.77; H 9.36. Found: C
3 2 2 3 2 3 9 16 3
6
2.72; H 9.38.
1
n-Dodecyl glycidate. H-NMR (400 MHz, CDCl at rt, ! in ppm): 4.21 (m, 2H, C H -CH -), 3.43 (dd,
3
10 21
2
1
H, J = 2.0 and 4.2 Hz, -CH-), 2.95 (dd, 1H, J = 2.0 and 6.6 Hz, -OCH CHCOO-), 2.82 (dd, 1H, J = 4.2
2
and 6.6 Hz, -OCH CHCOO-), 1.64 (m, 2H, -O-CH -CH ), 1.37 (m, 2H, -CH -C H -CH -), 0.9 (d, 3H, J =
2
2
2
2
9
18
2
1
3
7
.5 Hz, -CH -CH ). C-NMR (100 MHz, CDCl at rt, ! in ppm): 169.4 (>C=O), 65.9 (-COOCH -), 47.4
2 3 3 2
(
-CHCH - in epoxy ring), 46.4 (-CHCH - in epoxy ring), 32.0 (-COOCH CH -), 29.7 (-OCH CH CH -),
2 2 2 2 2 2 2
2
9.6-29.2 (-O(CH ) (CH ) -), 28.5 (CH CH CH CH-), 25.8 (CH CH CH -), 22.8 (CH CH -), 14.2 (CH -).
2 3 2 3 3 2 2 3 2 2 3 2 3
Anal. Calcd for C H O : C 70.27; H 11.01. Found: C 70.23; H 10.97.
1
5
28
3
8
10
10
Syntheses of methyl glycidate, ethyl glycidate, and n-butyl glycidate have already been reported.
ACKNOWLEDGEMENT
The authors thank Mr. Takeyoshi Takahashi for his contribution to elemental analysis.
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