Tetraethylammonium hydrogen carbonate: A cheap, efficient, and recyclable catalyst for transesterification reactions under solvent-free conditions

Article abstract of DOI:10.1080/00397911.2016.1233343

Tetraethylammonium hydrogen carbonate (TEAHC) was proven to be an efficient catalyst for transesterification reactions in the absence of solvent. The reaction between isopropenyl or ethyl acetate and an alcohol (not efficient in the absence of catalyst) was induced by the presence of TEAHC, which seems to assist the proton transfer from the alcohol to the ester, yielding the corresponding acetate in very good yields in the absence of any solvent. Moreover, the TEAHC can be recycled several times without significant loss in activity.

Full text of DOI:10.1080/00397911.2016.1233343

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Tetraethylammonium Hydrogen Carbonate:
A Cheap, Efficient and Recyclable Catalyst for
Transesterification Reactions Under Solvent-Free
Conditions
Isabella Chiarotto
To cite this article: Isabella Chiarotto (2016): Tetraethylammonium Hydrogen Carbonate: A
Cheap, Efficient and Recyclable Catalyst for Transesterification Reactions Under Solvent-Free
Conditions, Synthetic Communications, DOI: 10.1080/00397911.2016.1233343
To link to this article: http://dx.doi.org/10.1080/00397911.2016.1233343
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Date: 19 September 2016, At: 00:09

Tetraethylammonium Hydrogen Carbonate: A Cheap, Efficient and Recyclable
Catalyst for Transesterification Reactions Under Solvent-Free Conditions
Isabella Chiarotto1
1Dept. Scienze di Base e Applicate per l'Ingegneria, Sapienza University of Rome, Rome,
Italy
E-mail: isabella.chiarotto@uniroma1.it
Abstract
Tetraethylammonium hydrogen carbonate (TEAHC) was proved to be an efficient
catalyst for transesterification reactions in the absence of solvent. The reaction between
isopropenyl or ethyl acetate and an alcohol (not efficient in the absence of catalyst) was
induced by the presence of TEAHC which seems to assist the proton transfer from the
alcohol to the ester, yielding the corresponding acetate in very good yields in the absence
of any solvent. Moreover, the TEAHC can be recycled for several times without
significant loss in activity.
Graphical Abstract
KEYWORDS: Solvent free, Catalyst, Proton transfer, Tetraethylammonium hydrogen
carbonate, Transesterification
INTRODUCTION
1

The widespread presence of esters as intermediates in organic chemistry (fine chemicals,
natural products, polymers) and their utilization as protecting groups (carboxylic acids
and hydroxyl groups) have been often remarked. Usually, the synthesis of esters is
performed by the reaction of carboxylic acids or their derivatives with an excess amount
of an alcohol. The procedure requires the presence of catalysts or dehydrating agents
or/and harsh reaction conditions to proceed. [1-5]
Considering that the synthesis (a multistep process) often involves the generation of a
significant amount of wastes and by-products, the scientific community is strongly
interested in setting up alternative methodologies in accord with the current pressing
demand of a sustainable chemistry. [6-11]
Transesterification, a transformation of an ester into another ester through interchange of
the alkoxy moiety, has attracted much attention and it is regarded as a more advantageous
procedure than the ester synthesis from carboxylic acids and alcohols. In fact, the limited
solubility of some carboxylic acids in organic solvents and their lability could represent a
serious problem and it should be also noted that esters are generally more available than
corresponding carboxylic acids. [12-14]
The synthesis of esters via a transesterification process requires the utilization of catalysts
(acids, bases, N-heterocyclic carbenes, enzymes, organometallic catalysts) which often
present low selectivity and activity, high toxicity and cost and promote the formation of a
large number of by-products. [15-22]
2

Even though the utilization of strongly basic or acid catalysts leads to high conversions,
the presence of such species in the reaction mixture could be problematic for base or acid
sensitive substrates. [23] Therefore, remarkable efforts have been made to identify new
and more efficient catalysts to set up new simple and safe synthetic procedures.
As a consequence of what stated above, the catalytic activity of TEAHC, a weak and non
toxic base, was investigated under mild experimental conditions with the goal to develop
a new and environmentally friendly synthetic procedure affording esters via
transesterification reactions.
Recently, the application of electrogenerated N-heterocyclic carbene/room temperature
ionic liquid as a catalyst/solvent system for the transesterification, using isopropenyl or
ethyl acetate as acetyl donor was reported.[19]
RESULTS AND DISCUSSION
TEAHC 1a can be obtained by saturating a methanol solution of the commercially
available tetraethylammonium hydroxide (TEAOH) with carbon dioxide.[24] Due to the
higher cost of TEAOH/methanol solution, in the present work, tetraethylammonium
chloride (TEACl) was used as the quaternary organic ammonium salt to obtain the
corresponding hydrogen carbonate salt, by TEACl treating with an ion exchange resin to
avoid the use of any organic solvent, as reported by Bhatt and Gohil. [25] The hydrogen
carbonate anion-exchange resin can be easily prepared treating the resin (packed in a
3

chromatographic column) with an aqueous sodium hydrogen carbonate solution. The
anion metathesis, yielding the tetraethylammonium hydrogen carbonate, was thus carried
out in the column in aqueous solution. The water solvent was then removed yielding the
organic ammonium hydrogen carbonate as a dry solid, which was employed as the
catalyst for transesterification reaction. Therefore, the advantages of TEAHC 1a as
catalyst include its lack of sensitivity to moisture and oxygen, its ready availability, low
cost and toxicity.
However, we should consider that high conversions are difficult to achieve because the
transesterification process is an equilibrium reaction, so the fine-tuning of the reaction
parameters is fundamental to shift the equilibrium towards the desired direction.
Isopropenyl acetate 2a and benzyl alcohol 3a were used as model substrates to optimize
the reaction conditions, including different catalyst loadings, and catalytic/reactant ratios.
Moreover, in order to check the importance of the cation TEA+ in the acylation reaction,
other hydrogen carbonate salts, sodium 1b and potassium 1c, were tested.
In the Table 1 are reported the results obtained when a mixture of 2a and 3a, in different
ratios, was stirred for two hours at 60°C in the presence of the catalysts 1a-c to form ester
4aa. Initially, the reaction was carried out in the presence of 20 mol% of TEAHC 1a; by
using these conditions the reaction afforded the product 4aa in the moderate 45% yield
which was significantly improved up to 93% by increasing the catalyst loading to 30
mol% (Table 1, entry 2 vs. 3). The initial choice of isopropenyl acetate 2a as the
acylating agent was targeted to remove the alkoxide by-product from the equilibrium; in
4

fact, it is rapidly converted into the low-boiling acetone, shifting the equilibrium towards
the product. Thereafter, the effect of the ester/alcohol ratio on the equilibrium of
transesterification was investigated. When the amount of 3a was kept constant (1 mmol),
and the isopropenyl acetate amount was increased from 2 to 5 (Table 1, entries 1, 3, 4) an
increase in the yield of isolated 4aa from 33 to 99% was observed, in accord to the shift
of the transesterification equilibrium toward the product formation. The
transesterification with ethyl acetate is usually difficult to perform due to its low
electrophilicity and low boiling point. However, by employing the optimized reaction
conditions, (Table 1, entry 3), the acylation of benzyl alcohol with ethyl acetate 2b (Table
1, entry 7) was also performed, but the desired compound was obtained in lower yields
than those observed by using isopropenyl acetate as the starting material.
On this subject, we should consider that the synthesis of esters, via base-catalysed
transesterification reaction, requires the presence of a “shuttle” which is able to support
the proton transfer from the alcohol to the carbonyl oxygen of the ester. Recently, the
utilization of N-heterocyclic carbenes as uncharged basic “shuttle” was reported, the
related mechanism extensively discussed and the formation of the related intermediates
-
was suggested. [22, 26-27] The results reported in Table 1 prove that HCO3 could be an
efficient charged basic “shuttle” in transesterification reactions. Note that the value of the
-
pKa of HCO3 is considerable lower than that of NHC (pKa = 22-24 in water; 22 in
-
DMSO). [28-29] Therefore, HCO3 could be the select as basic “shuttle” when base
-
sensitive substrates are involved. Nevertheless, the utilization of HCO3 as the catalyst
requires a careful choice of reaction conditions such as the nature of the counter ion.
5

To verify the role of the tetraethylammonium cation in the synthetic procedure, the
acylation by applying other hydrogen carbonate salts, such as sodium 1b and potassium
1c was studied (Table 1, entries 5, 6 vs. 3). The yield of the isolated ester decreases in the
presence of small cations marked by a significant charge density and able to shield the
hydrogen carbonate anion with a consequent inhibition of its catalytic activity. The
comparison of the yields of the isolated products obtained in the presence of NaHCO3,
KHCO3 or TEAHC catalyst (Tab. 1, entries 5, 6, 3) reveals that the values of the radius of
the cations Na+ (1.02 Å), K+ (1.38 Å) and TEA+ (3.35 Å) strongly affect the catalytic
-
-
performance. [30] The “naked” anion HCO3 of TEAHC, i.e. HCO3 not shielded, could
support the proton transfer via a mechanism previously reported in the NHC-catalysed
transesterification. [22, 26-27] The proton transfer could be regarded as a concerted process
of cleavage and formation of oxygen-hydrogen bond, involving the structure I and IV
(Figure 1).
The overall mechanism rules out the formation of H2CO3 and the related dissociation
equilibrium. Accordingly, TEAHC was almost entirely recovered from the reaction
mixture. Finally, it is important to note that when the stronger base carbonate K2CO3 was
used as catalyst-parent in the reaction, the effect of the cation was not evidenced (Table
1, entry 6 and note).
To test the flexibility of the proposed methodology, the reactivity versus 2a of alcohols
3b-i was investigated. As expected, TEAHC proved to be an excellent catalyst for
6

transesterification. The results reported in the Table 2 showed that various primary
alcohols, as well as diols and secondary alcohols 3a-i, react with various esters 2a-d to
achieve the corresponding transesterification products.
The reaction of isopropenyl acetate 2a with primary alcohols 3a-f, run at 60 °C for 2 h
with 30 mol% of catalyst loading, gives corresponding esters with a yield range from
80%to 99% (Table 2, entries 1-6). The double acetylation of diol 3g with isopropenyl
acetate proceeds smoothly to provide the desired product in an excellent yield (Table 2,
entry 7). Compared with primary alcohols, the secondary alcohol 3h proceeds less
smoothly and affords lower yields of the desired compound under the same experimental
conditions (Table 2 entry 8). In general, primary alcohols are more active than secondary
alcohols, and aliphatic alcohols display higher reactivity in several cases. In addition to
aliphatic esters, methyl benzoate 2c also underwent transesterification. When the reaction
between methyl benzoate 2c and benzyl alcohol 3a was carried out in a 1:1 mole ratio
(being more valuable the starting substrates), the yield of benzyl benzoate 4ca was 65%
(Table 2, entry 9). Moreover, the reaction between methyl nicotinate 2d and 2-
diethylamino ethanol 3i gives the corresponding nicametate 4di, which has important
applications in cosmetic and pharmaceutical industries, in 84% yield (mole ratio 2d/3i
3:1), (Table 2, entry 10). [31]
Finally, to examine the recoverability and reusability of 1a, after the ethereal extraction
of the product (see experimental), the catalyst 1a was dried under reduced pressure
keeping it under high vacuum for 3 hour; after that it was reused directly for subsequent
7

four reaction cycles. The ester 4aa yield was very good for all the subsequent cycles
confirming the efficiency of this catalyst. The resulting yields of the isolated ester after
the five synthesis cycles are reported in Table 3.
The slight decrease in catalytic activity observed was attributed to the loss of small
quantities of 1a during each of the recycling processes.
EXPERIMENTAL
All reagents were purchased from suppliers (Aldrich, Fluka) and were used without any
further purification. 1H and 13C NMR spectra were recorded using a Bruker AC 200
spectrometer with CDCl3 as internal standard.
Synthesis Of Tetraethylammonium Hydrogen Carbonate
The ionic exchange chromatography column to generate the ammonium hydrogen
carbonates was a short glass column for chromatography of 0.18 m length and 0.01 m
diameter loaded with the resin Amberlite® IRA-400 chloride form (strongly basic gel-
type resin, quaternary ammonium functionality) from Sigma-Aldrich. This column was
packed using deionized distilled water and washed until chloride absence (checked with
AgNO3). This column was then slowly treated with 20 ml of NaHCO3 1 M salt solution.
The column was again washed with deionized distilled water until the eluent showed no
traces of the anion hydrogen carbonate (checked with HCl). A solution of
tetraethylammonium chloride (1mmol) in 2 mL of water was then introduced in the
column containing the hydrogen carbonate exchange resin and then the resin was washed
8

with water till the collection of 50 mL of solution. The solvent was evaporated under
reduced pressure and the resulting white solid was kept overnight under high vacuum.
The ionic exchange resin can be regenerated with the sodium hydrogen carbonate and
used several times
Typical Procedure For Transesterification Of Esters With Alcohols (4aa As An
Example)
In a typical procedure, in a capped vessel alcohol 3a (0.5 mmol) and ester 2a (1.5 mmol)
were added sequentially to the TEAHC (35.0 mg, 0.15 mmol); the reaction mixture was
stirred for 2h at 60 °C and then transferred in a round bottomed flask and concentrated
under reduced pressure. The residue mixture was then extracted with diethyl ether (3
times with 10 cm3). After removal of the solvent from the combined ethereal layers under
reduced pressure, the crude reaction mixture was analysed by 1H, 13C NMR and TLC. All
products were purified by using flash chromatography (n-hexane/ethyl acetate-95/5) and
identified on the basis of NMR spectroscopic analysis by comparison with reported data.
Synthesis Of Benzyl Benzoate 4ca
The procedure for the synthesis of 4ca was the same reported above, but 1 mmol of
benzyl alcohol and 1 mmol of methyl benzoate were added sequentially to the catalyst 1a
(30%mol). Ester 4ca was isolated in 65% yield. It was purified using flash
chromatography (hexane-CH2Cl2 90:10) and identified by NMR spectroscopy by
comparison with the data reported in the literature.
9

Synthesis Of Nicametate 4di
In the synthesis of nicametate 4di, 3 mmol of 2-diethylamino ethanol 3i and 1 mmol of
methyl nicotinate 2d were added to the catalyst 1a (30%mol), the corresponding ester 4di
was isolated in 84% yield. Ester was purified using flash chromatography (CH2Cl2-ethyl
acetate 95:5) and identified by NMR spectroscopy by comparison with the data reported
in the literature.
Reusability Of The Catalysts
To reach the main goal in this research, the reusability of the catalysts was examined in
the reported optimum conditions for four cycles. At the end of the reaction, after ethereal
extraction of product by simple filtration, the catalyst was recovered from the reaction
medium, dried at room temperature, and then reused for the next run. The results
demonstrated that after four cycles, the yield of reaction decreased from 93 to 84%. At
the end of the fourth run the amount of recovered catalyst was the 71% of the initial
quantity.
All the esters obtained are known compounds and their spectral data are in accordance
with those reported in the literature (see Supporting Information for full experimental
data)
CONCLUSION
In summary, tetraethylammonium hydrogen carbonate was used as the catalyst for the
transesterification of isopropenyl or ethyl acetate, with primary and secondary alcohols.
10

This protocol allows to avoid the use of strong bases and volatile organic solvents, and to
carry out this transformation under mild conditions. The catalyst showed good activity
for a wide scope of substrates, which were efficiently involved in the transesterification
process. Experimental data revealed that primary alcohols could be acylated more
efficiently than secondary alcohols. The catalyst recycling was studied and only a slight
loss in the yields was observed after five subsequent runs to render the system very
interesting for further applications in organic synthesis.
ACKNOWLEDGEMENTS
The author thanks Miur (Italy) and Sapienza University of Rome for financial support.
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13

Table 1. Hydrogen carbonate 1a-c catalysed transesterification of isopropenyl acetate
with benzyl alcohol. a
O
O
O
catalyst 1
2h , 60°C
+
Ph
OH
+
O
Ph
O
3a
2a
4aa
Entry Catalyst b Catalyst (mol%) 2a (mmol) Yield (%) 4aa c
1
2
3
4
5
6
7
30
20
30
30
30
30
30
2
3
3
5
3
3
3
33
45
93
99
5
1a
1a
1a
1a
1b
1c
1a
56d
75e
aReaction conditions: a mixture of 2a and benzyl alcohol 3a (1.0 mmol) was added to the
catalyst and stirred at 60 °C for 2h. b No product was isolated in the absence of catalyst. c
Isolated yields. d When the reaction was carried out with the stronger base K2CO3, in the
same conditions, the yield of 4aa was 98%. e Ethyl acetate 2b was used instead of
isopropenyl acetate.
14

Table 2. Transesterification of esters 2 with various alcohols 3 a
Entry
Ester
Alcohol
Product
Yield (%)b
93
O
O
1
OH
4aa
3a
2a
OH
NO2
2
3
87
2a
2a
4ab
3b
3c
OH
S
98
99
4ac
OH
4
O
3d
2a
2a
4ad
4ae
O
O
5
6
1-dodecanol 3e
9
89
80
O
O
O
2a
2a
OH
O
O
3f
4af
7c
O
HO
OH
3g
O
O
99
4ag
O
O
8
10d
2a
OH
3h
4ah
O
O
O
65e
84f
O
Ph
N
9
OH
2c
4ca
3a
O
O
O
N
HO
O
10
3i
N
2d
N
4di
15

aReaction conditions: solvent free, ester 2 (1.5 mmol) and alcohol 3 (0.5 mmol), TEAHC
30% mol, heated at 60 °C for 2h. b Isolated yields with respect to the starting alcohol. c 3g
(0.5mmol), 2a (3 mmol). d Yield determined by 1H NMR in CDCl3 based on starting
alcohol using 2,4-dinitrotoluene as an internal standard. e 3a (1 mmol) 2c (1 mmol). f 3i
(3 mmol) 2d (1 mmol).
16

Table 3. Reuse of catalyst 1a in the transesterification reaction of benzyl alcohol 3a with
isopropenyl acetate 2a with subsequent runs.a
Synthesis cycle Yield (%)
First
93b
91
86
90
84
Second
Third
Fourth
Fifth
aIn every run, the reaction conditions were the same of run one (for experimental
condition see Table 1, entry 1). b The result of the first cycle is the same shown in Table 2
entry 1.
17

Figure 1. Proposed TEAHC assisted mechanism for the transesterification.
18