Transesterification of α-substituted esters mediated by potassium carbonate

Article abstract of DOI:10.1055/s-2003-37113

α-Substituted esters were efficiently and easily transesterificated at room temperature in the presence of potassium carbonate. α-Halo esters can be transesterificated without substitution of the halogen atom.

Full text of DOI:10.1055/s-2003-37113

420
LETTER
Transesterification of a-Substituted Esters Mediated by Potassium Carbonate
T
ransesterification
o
of
α
-Substit
m
ute
d
E
sters Mediate
i
d by
P
n
otassium
C
ar
i
bonatek Jańczewski, Ludwik Synoradzki,* Marek Włostowski
Laboratory of Technological Processes, Faculty of Chemistry, Warsaw University of Technology, ul. Noakowskiego 3, 00-664 Warszawa,
Poland
Fax +48(22)6255317; E-mail: Ludwik.Synoradzki@chemix.ch.pw.edu.pl
Received 17 October 2002
reaction of 1a, the state of equilibrium was achieved at
Abstract: α-Substituted esters were efficiently and easily transes-
approximately the same level (Figure 1).
terificated at room temperature in the presence of potassium carbon-
ate. α-Halo esters can be transesterificated without substitution of
the halogen atom.
Key words: transesterification, catalysis, α-substituted esters, po-
tassium carbonate, haloesters
Transesterification is a well known reaction catalyzed
both by acids or bases.1 α-Hydroxy2,3 and α-benzyl
esters4–6 were reported to undergo transesterification in
the presence of K2CO3. Unsubstituted esters were also
found to react under these conditions however in this case
high temperature, pressure and a phase transfer catalyst
(PTC) were necessary.7
Figure 1 Transesterification of alkyl chloroacetates (1a, 1a′) with
2a (yield determined by HPLC)
We now would like to report that also some α-halo and
α-alkoxy methyl and ethyl esters enter readily the trans-
esterification reaction catalyzed by K2CO3 (Table 1). The
alcohol of our interest was N-(2-hydroxy-ethyl)-phthal-
imide (2a), however, other alcohols such as benzyl alco-
hol (2h) and ethoxyethanol (2i) also reacted with α-
chloroesters in good yields (Scheme 1).
We examined the influence of the PTC catalyst on the
reaction rate and yield. We found that the yield of the re-
action 1a with 2a did not depend on the presence of crown
ether or tetrabutylammonium bromide; the state of equi-
librium was reached at the same time with and without the
catalyst.
We also tried to extend the reaction range to unsubstituted
esters. We found that at room temperature ethyl acetate
(1g) did not react with 2a at all. When the reaction mixture
was refluxed for 200 hours, product 3g was obtained in
low (12%) yield. On the basis of this experiment we as-
sume that the presence of a substituent such as a halogen
atom or an alkoxy group at the α-position to the ester is
necessary and activates the transesterification reaction.
Scheme 1
The substitution reaction proceeds selectively at the car-
bon atom of the alkoxycarbonyl group and, surprisingly,
an exchange of the halogen atom in haloesters was not
observed under the reaction conditions.8
References
The reaction is carried out at room temperature and after
about 48 hours reaches the state of equilibrium.9a The
yield of product 3 can be easily increased when ethanol or
methanol, formed during the reaction, are removed by
distillation9b (Table 2).
(1) March, J. Advanced Organic Chemistry; Wiley and Sons:
New York, 1985, 351.
(2) Loder, D. J.; Teetars, W. O. US patent, US 2290128, 1939;
Chem. Abstr. 1943, 37, 387(7).
(3) Evans, D. A.; Tregay, S. W.; Burgey, C. S.; Paras, N. A.;
Vojkovsky, T. J. Am. Chem. Soc. 2000, 122, 7936.
(4) Artamonov, A. F.; Nigmatullina, F. S.; Aldabergenova, M.
T.; Dzhiembaev, B. Zh. Chem. Nat. Compd. 2000, 36, 345.
(5) Meyer, J. H.; Bartlett, P. A. J. Am. Chem. Soc. 1998, 120,
4600.
We compared the rate of the transesterification reaction of
ethyl (1a) and methyl (1a′) chloroacetates with 2a and
found that although the reaction of 1a′ was faster than the
(6) Kita, Y.; Egi, M.; Takada, T.; Tohma, H. Synthesis 1999,
885.
(7) Angeletti, E.; Tundo, P.; Venturello, P. J. Org. Chem. 1983,
48, 4106.
Synlett 2003, No. 3, Print: 19 02 2003.
Art Id.1437-2096,E;2003,0,02,0420,0422,ftx,en;G29602ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
Transesterification of α-Substituted Esters Mediated by Potassium Carbonate
421
Table 1 Transesterification – Conditions and Yields
Entry
Reactants
Molar ratio 1/2 Time (h)a
Yield of 3 (%),b (%)c
R3OH (2)
a
10
48
56, (88)
a′
as above
as above
10
5
24
24
53, (96)
52, (64)
b
c
as above
as above
10
10
24
48
60, (74)
45, (60)
d
e
f
as above
as above
as above
10
10
25
48
26, (51)
30, (46)
12d
48
g
200
h
i
5
5
72
48
46
38
a Reaction time (procedure I9a).
b Yield obtained according to procedure I9a (determined by GC or HPLC).
c Yield obtained according to procedure II9b (isolated product).
d Reaction was carried out under reflux conditions.
Table 2 Increase of Yield by Periodic Removal of Ethanol
(Entry a)9b
(8) The product of halogen substitution was obtained in case a
by application of a stronger base (sodium hydride). Similar
examples were reported: (a) Troostwijk, J. E.; Kellogg, R.
M. J. Chem. Soc., Chem. Commun. 1977, 932. (b) Asthana,
P.; Prasad, M.; Rastogi, S. N. Indian J. Chem., Sect. B 1987,
26, 330.
(9) (a) Procedure I (for 3a–i): The amount of 0.02 mol of
alcohol 2, 13.8 g (0.1 mol) of K2CO3, corresponding amount
of ester 1 (see Table 1) and 40 mL of THF were placed in a
round-bottomed flask. The reaction mixture was vigorously
Step I
48 h
Step II
Step III
Distillation + 48 h Distillation + 48 h
Observed
yield (%)a
56.2
79.8 88.4
a Yield determined by HPLC.
Synlett 2003, No. 3, 420–422 ISSN 0936-5214 © Thieme Stuttgart · New York

422
D. Jańczewski et al.
LETTER
stirred at r.t. (g – at boiling point) with a glass stirrer (blade
dimension 4 cm) at 1200 rpm. (b) Procedure II (for 3a–f):
Procedure II as in procedure I. After reaching the final
reaction time of procedure I, THF and alcohol 4 were
evaporated with a rotary evaporator (30 °C, 120 hPa, 1 h).
Fresh THF, 40 mL, was added to the solid residue, and the
reaction mixture was vigorously stirred again for the same
time. Evaporation and stirring were repeated once more.
(c) Isolation and Purification: The crude reaction mixture
was filtrated through a layer of celite and silica gel in order
to separate the potassium carbonate. Solvent, excess of ester
1, unreacted alcohol 2h, 2i and alcohol 4 were evaporated
with a rotary evaporator (40 °C, 3 hPa). In the case of 3a, 3h,
3i the products were pure enough for spectral analysis. In the
case of 3b–g unreacted 1 was recrystallized from
47.31; H, 2.93; N, 4.63. Mp: 100.3–101.5 °C. 2-
Chloropropionic Acid 2-(1,3-Dihydro-1,3-dioxo-2H-
isoindol-2-yl)ethyl Ester (3d): 1H NMR: δ = 7.79 (m, 4 H,
Ar), 4.45 (m, 2 H, NCH2CH2O), 4.35 (q, 1 H, J = 7 Hz,
CHClCH3), 4.00 (m, 2 H, NCH2CH2O), 1.65 (d, 3 H, J = 7
Hz, CHClCH3). IR: νC=O 1780, 1752, 1716 cm–1; νPh-H 728
cm–1. Anal. Calcd for C13H12ClNO4: C, 55.43; H, 4.29; N,
4.97. Found: C, 55.54; H, 3.99; N, 5.14. Mp: 49.1–49.7 °C.
Methoxyacetic Acid 2-(1,3-Dihydro-1,3-dioxo-2H-
isoindol-2-yl)ethyl Ester (3e): 1H NMR: δ = 7.77 (m, 4 H,
Ar), 4.39 (t, 2 H, J = 5.3 Hz, NCH2CH2O), 3.98 (s, 2 H,
COCH2O), 3.95 (t, 2 H, J = 5.3 Hz, NCH2CH2O), 3.39 (d, 3
H, OCH3). IR: νC=O 1772, 1752, 1712 cm–1; νPh-H 728 cm–1.
Anal. Calcd for C13H13NO5: C, 59.31; H, 4.98; N,
5.32,.Found: C, 59.65; H, 5.18; N, 5.18. Mp: 67.6–67.9 °C.
Ethoxyacetic Acid 2-(1,3-Dihydro-1,3-dioxo-2H-
isoindol-2-yl)ethyl Ester (3f):10 1H NMR: δ = 7.79 (m, 4 H,
Ar), 4.40 (t, 2 H, J = 5.2 Hz, NCH2CH2O), 4.04 (s, 2 H,
COCH2O), 3.97 (t, 2 H, J = 5.2 Hz, NCH2CH2O), 3.56 (q, 2
H, J = 7 Hz, OCH2CH3), 1.20 (t, 3 H, J = 7 Hz, OCH2CH3).
IR: νC=O 1776, 1760, 1712 cm–1; νPh-H 720 cm–1. Mp: 54.5–
54.8 °C. Acetic Acid 2-(1,3-Dihydro-1,3-dioxo-2H-
isoindol-2-yl)ethyl Ester (3g):11 1H NMR: δ = 7.79 (m, 4 H,
Ar), 4.31 (t, 2 H, J = 5.4 Hz, NCH2CH2O), 3.95 (t, 2 H,
J = 5.4 Hz, NCH2CH2O), 2.01 (s, 3 H, CH3). IR: νC=O 1776,
1740, 1712 cm–1. νPh-H 720 cm–1. Mp: 88.1–88.4 °C.
Chloroacetic Acid Phenylmethyl Ester (3h):12 1H NMR:
δ = 7.38 (m, 5 H, Ar), 5.22 (s, 2 H, PhCH2O), 4.10 (s, 2 H,
COCH2Cl). IR: νC=O 1756 cm–1; νPh-H 792, 752, 704 cm–1. 2-
Chloropiopionic Acid-2-ethoxyethyl Ester (3i): 1H NMR:
δ = 4.42 (q, 1 H, J = 7 Hz, CHClCH3), 4.30 (m, 2 H,
CH2CO), 3.65 (m, 2 H, OCH2CH2), 3.52 (q, 2 H, J = 7 Hz,
CH3CH2O), 1.68 (d, 3 H, J = 7 Hz, CHClCH3), 1.90 (t, 3 H,
J = 7 Hz, CH3CH2O). IR: νC=O 1752 cm–1.
dichloromethane, the filtrate was evaporated under reduced
pressure to give the product. Compounds 3a–3f were
additionally crystallized from ethanol at –10 °C for mp,
spectral and CHN analysis. (d) Spectroscopic and
Analytical Data: 1H NMR: (200 MHz, CDCl3), IR: (KBr).
Chloroacetic Acid 2-(1,3-dihydro-1,3-dioxo-2H-isoindol-
2-yl)ethyl Ester (3a): 1H NMR: δ = 7.77 (m, 4 H, Ar), 4.41
(t, 2 H, J = 5.2 Hz, NCH2CH2O), 4.03 (s, 2 H, COCH2Cl),
3.96 (t, 2 H, J = 5.2 Hz, NCH2CH2O). IR: νC=O 1770, 1752,
1708 cm–1; νPh-H 722 cm–1. Anal. Calcd for C12H10ClNO4: C,
53.85; H, 3.77; Cl, 13.25;, N, 5.23. Found: C, 53.82; H, 3.97;
Cl, 13.23; N, 5.01. Mp: 129.8–130.5 °C. Bromoacetic Acid
2-(1,3-Dihydro-1,3-dioxo-2H-isoindol-2-yl)ethyl Ester
(3b): 1H NMR: δ = 7.80 (m, 4 H, Ar), 4.42 (t, 2 H, J = 5.3
Hz, NCH2CH2O), 4.00 (t, 2 H, J = 5.3 Hz, NCH2CH2O),
3.82 (s, 2 H, CH2Br). IR: νC=O 1772, 1748, 1708 cm–1; νPh-H
724 cm–1. Anal. Calcd for C12H10BrNO4: C, 46.18; H, 3.23;
N, 4.49. Found: C, 46.17; H, 3.29; N, 4.28. Mp: 124 °C.
Dichloroacetic Acid 2-(1,3-Dihydro-1,3-dioxo-2H-
isoindol-2-yl)ethyl Ester (3c): 1H NMR: δ = 7.79 (m, 4 H,
Ar), 5.92 (s, 1 H, COCHCl2), 4.51 (t, 2 H, J = 5.3 Hz,
NCH2CH2O), 4.03 (t, 2 H, J = 5.3 Hz, NCH2CH2O). IR: νC=O
1776, 1760, 1720, 1708 cm–1; νPh-H 724 cm–1. Anal. Calcd
for C12H9Cl2NO4: C, 47.71; H, 3.00; N, 4.64. Found: C,
(10) Maruyama, K.; Ogawa, T.; Kubo, Y.; Araki, T. J. Chem.
Soc., Perkin Trans. 2 1985, 1, 2025.
(11) Crane, C. W.; Rydon, N. H. J. Chem. Soc. 1947, 527.
(12) Curran, D. P.; Jasperse, C. P.; Totleben, M. J. J. Org. Chem.
1991, 56, 7169.
Synlett 2003, No. 3, 420–422 ISSN 0936-5214 © Thieme Stuttgart · New York