Synthesis of Fatty Acetoacetates Under Microwave Irradiation Catalysed by Sulfamic Acid in a Solvent-Free System

Article abstract of DOI:10.1007/s11746-016-2879-5

The 1,3-dicarbonyl compounds are important building blocks to obtain products with various biological activities and technological applications. In this work, we used a simple transesterification method to develop fatty acetoacetates in a solvent-free medium using a green catalyst, sulfamic acid (NH₂SO₃H), under microwave irradiation. The experimental results demonstrate good yields in a short reaction time (13?min), which makes this method an efficient approach to synthesize fatty acetoacetates from a wide range of saturated, unsaturated, and polyunsaturated long chain fatty alcohols, and ricinoleic derivatives. Experiments of recycling of the catalyst were performed and no decrease in catalytic activity of sulfamic acid was observed.

Full text of DOI:10.1007/s11746-016-2879-5

J Am Oil Chem Soc
DOI 10.1007/s11746-016-2879-5
ORIGINAL PAPER
Synthesis of Fatty Acetoacetates Under Microwave Irradiation
Catalysed by Sulfamic Acid in a Solvent‑Free System
Andressa C. H. Weber1 · Thaís C. Batista1 · Bruno Gonçalves1 · Carolina R. L. Hack1 ·
Larissa M. Porciuncula1 · Tamara G. M. Treptow1 · Caroline Da R. Montes D’Oca2 ·
Dennis Russowsky2 · Marcelo G. Montes D’Oca1
Received: 1 December 2015 / Revised: 28 July 2016 / Accepted: 28 July 2016
© AOCS 2016
Abstract The 1,3-dicarbonyl compounds are important
building blocks to obtain products with various biological
activities and technological applications. In this work, we
used a simple transesterification method to develop fatty
acetoacetates in a solvent-free medium using a green cata-
lyst, sulfamic acid (NH2SO3H), under microwave irradia-
tion. The experimental results demonstrate good yields in a
short reaction time (13 min), which makes this method an
efficient approach to synthesize fatty acetoacetates from a
wide range of saturated, unsaturated, and polyunsaturated
long chain fatty alcohols, and ricinoleic derivatives. Experi-
ments of recycling of the catalyst were performed and no
decrease in catalytic activity of sulfamic acid was observed.
of polymers, drugs and biologically active compounds [1–
3]. They have also been studied as biofuel additives [4].
Using acetoacetates as the building blocks in multicompo-
nent reactions (MCR) [5] yields several different structures
based on the dihydropyridinone (DHPM) or dihydropyridine
(DHP) skeleton, which creates an extensive library of com-
pounds with various biological activities [6–10]. MCR have
been recognized for their high convergence, atomic economy
and operational simplicity and are emphasized as important
tools to synthesize high-molecular-complexity compounds in
accordance with green chemistry principles [2, 11].
The transesterification reaction to synthesize acetoac-
etates is a notably useful tool in organic synthesis, and
various methods have been reported to affect the transester-
ification of methyl or tert-butyl acetoacetates. The uncata-
lyzed transesterification of acetoacetates requires the use of
either an excess of ketoester or a longer reaction time and a
high boiling alcohols or solvents limiting their usage [12].
According to the literature, the transesterification process
to synthesize β-ketoesters under solvent-free conditions
without catalysis results in high yields when excess alcohol
is used at a high temperature [13]. In addition, the rate of
transesterification of acetoacetates is significantly affected
by steric factors; thus, tertiary alcohols are less active. Pri-
mary, secondary, and tertiary alcohols have been tested in
the presence of molecular sieves, which results in good ace-
toacetate yields [12]. The catalysts in the transesterification
reaction vary and include new silica-based hybrid materials,
triethylamine, boric acid, and triphenylphosphine [14–17].
However, the development of a new method that enables
transesterification in milder conditions should heighten the
synthetic potential of the reaction. Considering the impor-
tance of acetoacetates, cleaner methodologies have been
studied for their synthesis; solvent-free conditions [18] and
replacement of catalysts [13] render the protocol to obtain
Keywords Castor oil · Renewable resources ·
Transesterification reaction · 1,3-dicarbonyl compounds ·
Microwave-assisted
Introduction
The 1,3-dicarbonyl compounds, such as acetoacetates or
β-ketoesters, are important building blocks in the synthesis
Electronic supplementary material The online version of this
article (doi:10.1007/s11746-016-2879-5) contains supplementary
material, which is available to authorized users.
* Marcelo G. Montes D’Oca
dqmdoca@furg.br
1
Laboratório Kolbe de Síntese Orgânica, Escola de Química e
Alimentos, Universidade Federal do Rio Grande, Av. Italia,
Km 08, Rio Grande, RS, Brazil
2
Laboratório de Sínteses Orgânicas, Instituto de Química,
Universidade Federal do Rio Grande do Sul, Av. Bento
Gonçalves 9500, Porto Alegre, RS 91501-970, Brazil
1 3

J Am Oil Chem Soc
O
O
1,3-dicarbonyl compounds an environmentally friendly
process [19, 20]. The employment of enzymatic cataly-
sis have been reported, because this approach allows high
yields under mild conditions, thereby fulfilling the general
principles of green chemistry [21, 22]. The use of heteroge-
neous catalytic systems, such as sulfamic acid (NH2SO3H),
is wanted in green chemistry [23]. This relatively stable,
white crystalline solid is odorless, non-volatile, non-hygro-
scopic, non-corrosive, and low-cost, and it is a highly effi-
cient catalyst in organic synthesis [15, 24, 25]. Sulfamic
acid and alcohol as an organic reaction promoter system
have been proven to have remarkable efficiency because
of a synergistic effect of sulfamic acid in zwitterionic form
(NH3+SO3−), as demonstrated in the synthesis of quinoxa-
lines [26], benzimidazole derivatives [27] and 2,3-dihy-
droquinazolinones [28]. According to the literature, an
efficient approach to 1,4-dihydropyridines with new substi-
tuted pyrazole involves the synthesis via a three-component
reaction of pyrazolyl aldehyde, β-ketoester, and ammonium
acetate under sulfamic acid catalysis [29].
Ultrasound and microwave (MW) radiation systems
have been increasingly used in organic reactions, and they
are considered clean and easy to operate [30]. Furthermore,
they can obtain products in short reaction times and pro-
duce higher energy usage than the traditional heating tech-
niques [31–34]. Another advantage is that microwaves can
promote infeasible transformations to traditional heating
after energy is directly applied to the reactants, and global
warming can be minimized using simultaneous colds [35].
Recently, we demonstrated for the first time the syn-
thesis of new fatty β-ketoesters from fatty acid families
in good yields [36]. A series of fatty β-ketoesters were
obtained from several fatty acids and Meldrum’s acid using
N,N-dicyclohexylcarbodiimide (DCC) and dimethylamino-
pyridine (DMAP).
O
O
NH2SO3H
R1 OH
+
OR1
OMe
MW or
conventional heating
methyl
Fatty alcohols
Fatty acetoacetates
acetoacetate
1a-l
2a-l
( )8
c
( )6
( )10
d
( )12
e
( )14
f
( )16
g
( )4
a
b
( )7
R1
=
( )7
( )7
( )7
( )4
( )7
h
j
l
i
O
( )7
( )7
( )5
k
Scheme 1 Synthesis of fatty acetoacetates 2a‑l under MW or con-
ventional heating catalyzed by NH2SO3H
Column chromatography was performed using a Silica Gel
60 A (ACROS Organics, 0.035–0.070 mesh). The reactions
were monitored using thin-layer chromatography (TLC)
with plates containing silica gel (Merck 60GF245), and the
spots were visualized using iodine. The yields refer to chro-
matographically and spectroscopically homogeneous mate-
rials. The melting points were obtained using a Fisatom
430D apparatus and were uncorrected. The infrared (IR)
spectra were measured using a Schimadzu PRESTIGIE-21
FT-IR spectrophotometer. The NMR spectra were recorded
using a Varian VNMRS 300 spectrometer (1H at 300 MHz
and 13C at 75.5 MHz) in CDCl3 as solvent. The chemical
shift data are reported in units of δ (ppm) downfield from
tetramethylsilane (TMS), which was used as an internal
standard. The coupling constants (3J) are reported in Hz
and refer to apparent peak multiplicities.
General Procedure to Synthesize Fatty Acetoacetates 2a‑l
in Conventional Heating
In a continuation of our studies to synthesize com-
pounds from renewable resources [37–40], we describe
here the synthesis of fatty acetoacetates 2a‑l derivatives
from renewable saturated, unsaturated, polyunsaturated and
ricinoleic fatty acids using the transesterification reaction
under sulfamic acid (NH2SO3H) catalysis and solvent-free
conditions using long chain alcohols (Scheme 1).
A mixture of fatty alcohol (1 mmol), methyl acetoacetate
(4 mmol) and NH2SO3H (0.3 mol%) in a solvent-free con-
dition was stirred for 6 h at 80 °C. Then, 3 × 10 mL of
ethyl acetate was added, and the residual catalyst was fil-
trated. The organic layer was washed (3 × 10 mL), and
dried with Mg2SO4. The solvent was removed by rotary
evaporation, and the obtained residue was purified using
flash column chromatography on a silica gel 35–70 µm
thick and the eluent hexane/ethyl acetate (97:3) to afford
fatty acetoacetates 2a‑l.
Experimental Procedures
Apparatus and Chemistry
General Procedure to Synthesize Fatty Acetoacetates 2a‑l
Under MW Irradiation
The fatty acids and sulfamic acid (98 wt%) were supplied
by Aldrich Chemical Co. Ricinoleic acid (cis-C18:1,12-
OH) was obtained from castor oil or via castor oil bio-
diesel hydrolysis. The other reagents were purchased from
Aldrich Chemical Co. and used without further purification.
A mixture of fatty alcohol (1 mmol), methyl acetoacetate
(4 mmol) and NH2SO3H (0.3 mol%) in a solvent-free
1 3

J Am Oil Chem Soc
condition was stirred for 30 s. Then, in a max power mode
at 300 W and 120 °C, the reaction occurred for 13 min in
an appropriate 10-mL tube in a Discovery CEL Discovery
& Explorer SP microwave. Subsequently, 3 × 10 mL of
ethyl acetate was added, and the residual catalyst was fil-
tered. The organic layer was washed (3 × 10 mL) and dried
with Mg2SO4. The solvent was removed by rotary evapora-
tion, and the obtained residue was purified using flash col-
umn chromatography on a silica gel 35–70 µm thick with
the eluent hexane/ethyl acetate (97:3) to afford fatty ace-
toacetates 2a‑l.
Tetradecyl 3‑oxobutanoate (2e)
MW 298.46 g mol−1; White solid; m.p. 28–30 °C; Yield
75 %; FT-IR (KBr, ν = cm−1): 1471, 1710, 1734, 2848,
1
2916; H NMR (300 MHz, CDCl3) δ (ppm): 4.15 (t, 2H,
J = 6.0 Hz), 3.46 (s, 2H), 2.28 (s, 3 H), 1.65 (m, 2 H), 1.27
(m, 20H), 0.89 (t, 3H, J = 6.0 Hz); 13C NMR (75 MHz,
CDCl3) δ (ppm): 200.6, 167.2, 65.6, 50.1, 31.9, 30.1, 29.6
(3C), 29.4, 29.3 (2C), 29.2 (2C), 28.4, 25.7, 22.6, 14.1.
Hexadecyl 3‑oxobutanoate (2f)
All procedures applying these methods were performed
in triplicate
MW 326.51 g mol−1; White solid; m.p. 40–41 °C; Yield
85 %; FT-IR (KBr, ν = cm−1): 1473, 1710, 1734, 2848,
1
Hexyl 3‑oxobutanoate (2a)
2912, 2953; H NMR (300 MHz, CDCl3) δ (ppm): 4.13
(t, 2H, J = 7.5 Hz), 3.45 (s, 2 H), 2.27 (s, 3 H), 1.64 (m,
2 H), 1.26 (m, 26 H, 0.88 (t, 3H, J = 6.0 Hz); 13C NMR
(75 MHz, CDCl3) δ (ppm): 200.6, 167.1, 65.5, 50.1, 31.9,
30.1, 29.6 (4C), 29.5 (2C), 29.4 (2C), 29.3, 29.1, 28.4,
25.8, 22.6, 14.1.
MW 186.25 g mol−1; Colorless oil; Yield 81 %; FT-IR
(KBr, ν = cm−1): 1467, 1714, 1743, 2856, 2927, 2954; 1H
NMR (300 MHz, CDCl3) δ (ppm): 4.13 (t, 2H, J = 6.0 Hz),
3.44 (s, 2 H), 2.26 (s, 3 H), 1.64 (m, 2 H), 1.28 (m, 6H),
0.87 (t, 3H, J = 6.0 Hz); 13C NMR (75 MHz, CDCl3): δ
(ppm) 200.5, 167.2, 65.5, 50.1, 31.3, 30.1, 28.4, 25.4, 22.4,
13.9.
Octadecyl 3‑oxobutanoate (2g)
MW 354.57 g mol−1; White solid; m.p. 45–46 °C; Yield
Octyl 3‑oxobutanoate (2b)
86 %; FT-IR (KBr, ν = cm−1): 1465, 1705, 1741, 2848,
1
2916, 2953; H NMR (300 MHz, CDCl3) δ (ppm): 4.15 (t,
MW 214.30 g mol−1; Colorless oil; Yield 80 %; FT-IR
(KBr, ν = cm−1): 1454, 1712, 1745, 2858, 2931, 2958; 1H
NMR (300 MHz, CDCl3) δ (ppm): 4.04 (m, 2H), 3.44 (s,
2H), 2.25 (s, 3 H), 1.57 (m, 2 H), 1.27–1.39 (m, 10H), 0.87
(t, 3H, J = 7.5 Hz); 13C NMR (75 MHz, CDCl3) δ (ppm):
200.4, 167.1, 67.6, 50.0, 38.5, 30.1, 30.0, 28.7, 23.5, 22.8,
13.9, 10.8.
2H, J = 6.0 Hz, 3.46 (s, 2 H), 2.28 (s, 3 H), 1.65 (m, 2
H), 1.27 (m, 28 H), 0.89 (t, 3H, J = 6.0 Hz); 13C NMR
(75 MHz, CDCl3) δ (ppm): 200.1, 166.7, 65.1, 49.6, 31.4,
29.6, 29.2 (3C), 29.1 (3C), 29.0 (2C), 28.9 (2C), 28.7 (2C),
27.9, 25.3, 22.2, 13.6.
(9Z)‑Octadec‑9‑en‑1‑yl 3‑oxobutanoate (2h)
Decyl 3‑oxobutanoate (2c)
MW 352.55 g mol−1; Yellow oil; Yield 80 %; FT-IR (KBr,
ν = cm−1): 1465, 1647, 1714, 1743, 2852, 2924; 1H NMR
(300 MHz, CDCl3) δ (ppm): 5.37 (m, 2 H), 4.15 (t, 2H,
J = 7.5 Hz), 3.47 (s, 2 H), 2.29 (s, 3H), 2.03 (m, 4 H), 1.66
(m, 2 H), 1.29–1.32 (m, 22 H), 0.90 (t, 3H, J = 6.0 Hz);
13C NMR (75 MHz, CDCl3) δ (ppm): 200.4, 167.1, 129.8,
129.6, 65.4, 49.9, 32.5, 31.8, 29.6 (2C), 29.5, 29.4 (2C),
29.2 (2C), 29.1, 28.4, 27.1 (2C), 25.7, 22.6, 13.9.
MW 242.35 g mol−1; Colorless oil; Yield 75 %; FT-IR
(KBr, ν = cm−1): 1463, 1745, 2852, 2924; 1H NMR
(300 MHz, CDCl3) δ (ppm): 4.11 (t, 2H, J = 6.0 Hz), 3.43
(s, 2H), 2.25 (s, 3 H), 1.62 (m, 2 H), 1.25 (m, 12H), 0.86
(t, 3H, J = 6.0 Hz); 13C NMR (75 MHz, CDCl3) δ (ppm):
200.5, 167.1, 65.5, 50.0, 31.8, 29.9, 29.4, 29.3, 29.2, 29.1,
28.4, 25.7, 22.6, 13.9.
(9E)‑Octadec‑9‑en‑1‑yl 3‑oxobutanoate (2i)
Dodecyl 3‑oxobutanoate (2d)
MW 352.55 g mol−1; White solid; m.p. 30–32 °C; Yield
MW 270.41 g mol−1; Colorless oil; Yield 73 %; FT-IR
(KBr, ν = cm−1): 1465, 1716, 1743, 2852, 2922; 1H NMR
(300 MHz, CDCl3) δ (ppm): 4.15 (t, 2H, J = 6.0 Hz), 3.46
(s, 2H), 2.28 (s, 3 H), 1.65 (m, 2 H), 1.27 (m, 16H), 0.89
(t, 3H, J = 6.0 Hz); 13C NMR (75 MHz, CDCl3) δ (ppm):
200.6, 167.2, 65.6, 50.1, 31.9, 30.1, 29.6 (2C), 29.5, 29.4,
29.3, 29.2, 28.4, 25.8, 22.6, 14.1.
75 %; FT-IR (KBr, ν = cm−1): 1458, 1656, 1726, 1743,
1
2852, 2924; H NMR (300 MHz, CDCl3) δ (ppm): 5.39
(m, 2 H), 4.14 (t, 2H, J = 6.0 Hz), 3.45 (s, 2H), 2.28 (s, 3
H), 1.97 (m, 4H), 1.65 (m, 2H), 1.27 (m, 22 H), 0.89 (t, 3H,
J = 6.0 Hz); 13C NMR (75 MHz, CDCl3) δ (ppm): 200.5,
167.1, 130.3, 130.1, 65.5, 50.0, 32.5 (2C), 31.8, 30.0, 29.6
(2C), 29.5, 29.4; 29.3, 29.2, 29.1, 28.9, 28.4, 25.7, 22.6, 14.0.
1 3

J Am Oil Chem Soc
O
O
(9Z,12Z)‑Octadeca‑9,12‑dien‑1‑yl 3‑oxobutanoate (2j)
NH2SO3H
O
O
mol%
(
)
+
( )14
OH
( )14
O
OMe
MW 350.54 g mol−1; Yellow oil; Yield 79 %; FT-IR (KBr,
ν = cm−1): 1465, 1662, 1728, 1743, 2854, 2926, 3008; 1H
NMR (300 MHz, CDCl3) δ (ppm): 5.36 (m, 4H), 4.14 (t,
2H, J = 7.5 Hz), 3.45 (s, 2 H), 2.77 (t, 2H, J = 6.0 Hz),
2.27 (s, 3 H), 2.03 (q, 4H, J = 6.0 Hz), 1.64 (m, 2 H), 1.30
(m, 16 H), 0.89 (t, 3H, J = 6.0 Hz); 13C NMR (100 MHz,
CDCl3) δ (ppm): 200.6, 167.1, 130.1, 129.9, 127.9, 127.8,
65.5, 50.1, 31.4, 30.1, 29.5, 29.3, 29.2, 29.1 (2C), 28.4,
27.1, 25.7, 25.5, 22.6, 22.5, 14.0.
Temperature
2f
1f
Time
Scheme 2 Synthesis of fatty acetoacetate 2f under conventional heat-
ing catalyzed by NH2SO3H
time, temperatures, catalysis loading, and stoichiometry
amounts.
The reactions were monitored using thin layer chroma-
tography (TLC), and the results are shown in Table 1. Ini-
tially, we evaluated the synthesis of 2f using conventional
heating (80 °C) in a solvent-free medium with 10 mol% of
sulfamic acid for 3 h with constant stirring (Table 1, entry
1) according to the described experimental protocol in the
literature using ionic liquid [20]. However, in our hands,
this protocol has provided notably low yield using palmitic
alcohol (1f) a long chain alcohol.
From these results, the effect of 1,3-dicarbonilic excess
in a longer reaction time was studied (Table 1, entries 2–7).
In addition, the reaction was investigated in the presence of
different solvents (Table 1, entries 5 and 6), but all tested
conditions led to lower yields and the starting materials
were recovered and no ketalization product of β-carbonyl
[20] of the methyl acetoacetate with fatty alcohol was
detected. However, the use of 4 equivalents of 1,3-dycar-
bonilic in a solvent-free medium had better yields (Table 1,
entry 7). Afterward, the catalyst loading was also tested.
The reactions were performed in the presence of 20 mol%
and 30 mol% of sulfamic acid (Table 1, entries 8–11).
According to Table 1, it was possible to observe better
(9Z,12Z,15Z)‑Octadeca‑9,12,15‑trien‑1‑yl
3‑oxobutanoate (2k)
MW 348.52 g mol−1; Yellow oil; Yield 76 %; FT-IR (KBr,
ν = cm−1): 1435, 1656, 1732, 1759, 2870, 2922, 2954,
1
2999, 3062; H NMR (300 MHz, CDCl3) δ (ppm): 5.34
(m, 6H), 4.14 (t, 2H, J = 7.5 Hz), 3.45 (s, 2 H), 2.77 (t,
4H, J = 6.0 Hz), 2.27 (s, 3 H), 2.05 (m, 4H), 1.64 (m, 2
H), 1.30 (m, 10 H), 0.89 (t, 3H, J = 6.0 Hz); 13C NMR
(75 MHz, CDCl3) δ (ppm): 200.1, 166.7, 129.7, 128.6 (3C),
127.5 (2C), 65.0, 49.6, 31.0, 29.1, 28.9, 28.7, 27.9, 26.7
(3C), 25.3, 25.1, 22.1, 13.6.
(12R,9Z)‑12‑Methoxyoctadec‑9‑en‑1‑yl 3‑oxobutanoate
(2l)
MW 382.58 g mol−1; Yellow oil; Yield 75 %; FT-IR (KBr,
ν = cm−1): 1238, 1458, 1645, 1726, 1743, 2852, 2926,
3005; 1H NMR (300 MHz, CDCl3) δ (ppm): 5.42 (m, 2H),
4.14 (t, 2H, J = 6.0 Hz), 3.45 (s, 2 H), 3.34 (s, 3H), 3.17
(m, 1H), 2.27 (s, 3 H), 2.25 (m, 2H), 2.04 (m, 2H), 1.64 (m,
2 H), 1.45 (m, 2H), 1.28 (m, 18H), 0.88 (t, 3H, J = 6.0 Hz);
13C NMR (75 MHz, CDCl3) δ (ppm): 200.5, 167.2, 131.7,
125.4, 80.9, 65.5, 56.5, 50.1, 33.5, 31.8, 31.0, 30.1, 29.5,
29.4, 29.3, 29.2, 29.1, 28.4, 27.4, 25.7, 25.3, 22.6, 14.0;
[α]2D0 = +13.02 (c 0.41, CH2Cl2).
Table 1 Experimental screening to synthesis of fatty acetoacetate 2f
catalyzed by NH2SO3H under conventional heating
Entry Fatty
alcohol
Methyl ace- NH2SO3H
T (h) Fatty ace-
toacetate
toacetate
(equiv)
(mol%), solvent
(1f,
(2f, %)a
equiv)
Results and Discussion
1
1.2
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
2.0
3.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
10, Solvent-free
10, Solvent-free
10, Solvent-free
10, Solvent-free
10, Hexane
3
6
6
3
3
3
6
3
6
6
9
35
40
60
65
58
61
75
60
69
83
78
2
The synthesis of fatty acetoacetate was investigated with
conventional heating and microwave irradiation in a sol-
vent-free medium with fatty alcohols and sulfamic acid
catalysis, which has been studied in our group as an effec-
tive catalyst for several organic transformations.
The fatty alcohols precursors 1a‑k were synthe-
sized from the reduction of methyl esters [41] accord-
ing to the literature [42, 43]. Then, initial tests to opti-
mize the experimental conditions were performed using
palmitic alcohol (1f, Scheme 2) as the template under
different experimental conditions such as the reaction
3
4
5
6
10, CH2Cl2
7
10, Solvent-free
20, Solvent-free
20, Solvent-free
30, Solvent-free
30, Solvent-free
8
9
10
11
a
Isolated yield after column chromatography on a silica gel
1 3

J Am Oil Chem Soc
Table 2 Synthesis of fatty-1,3-dicarbonyl 2a‑l in a solvent-free medium catalyzed by 30 mol% NH2SO3H under conventional heating (80 °C,
6 h) and MW irradiation (120 °C, 13 min, 300 W)
Entry
Alcohol
1a
Fatty acetoacetate
Conventional
heating
MW
irradiation
Melting
point
O
O
1
2
79%
77%
81%
80%
oil[12]
O
O
( )
4
2a
O
O
O
1b
oil[19]
( )6
2b
O
3
4
5
6
7
1c
1d
1e
1f
68%
69%
69%
83%
85%
75%
73%
75%
85%
86%
oil
O
( )8
2c
O
O
O
O
O
oil[12, 46]
O
O
O
O
( )
1
0
2d
O
28-30 °C
40-41 °C[6]
45-46 °C[6]
( )12
2e
O
( )14
2f
O
1g
( )
1
6
2g
O
O
O
O
8
9
1h
1i
78%
73%
75%
72%
80%
75%
79%
76%
oil[6]
30-32 °C
oil
O
( )7
( )7
2h
2i
( )7
O
( )7
O
O
10
11
1j
O
( )
7
( )
4
2j
O
O
1k
oil
O
( )7
2k
O
O
O
12
1l
70%
75%
oil
O
( )5
( )7
2l
1 3

J Am Oil Chem Soc
results employing 30 mol% of catalyst, at a temperature of
80 °C and a reaction time of 6 h under conventional heat-
ing conditions (Table 1, entry 10). In addition, we evaluated
the synthesis of 2f using conventional heating at 100 and
120 °C in a solvent-free medium with 30 % sulfamic acid.
However, within the experimental conditions, an increase
in the temperature not significantly increases the yield of
2f.
These findings using conventional heating were used as
initial protocol for the investigation of reaction behavior
under microwave irradiation conditions to synthesis of fatty
acetoacetates. Were evaluated the effect of the temperature
(80–150 °C), time (5 min–2 h) and power (100–300 W) of
the microwave irradiation system in the transesterification
reaction, in a solvent-free medium with 30 mol% sulfamic
acid catalyst. The reaction course was monitored by TLC
and the best results were observed with 30 s of pre-stir-
ring, at 120 °C of temperature, reaction time of 13 min and
300 W power. This protocol resulted in 80 % yield of 2f
from palmitic alcohol (1f).
(12-hydroxy-9-cis-octadecenoic acid), which is the major
constituent (80–90 %) of castor oil (Ricinus communis)
[44] and an uncommon fatty acid that contains a double
bond and a hydroxyl group, were synthesized. According
to previous work, the 12-hydroxy-methyl ricinoleate was
obtained in 90 % yield from castor oil via the transesterifi-
cation reaction (Scheme 3) [45].
The 12-hydroxy-methyl ricinoleate was protected with
CH3I to obtain the corresponding alcohol 1l (Scheme 3).
Then, the transesterification reaction from 1l and methyl
acetoacetate under sulfamic acid catalysis led to the forma-
tion of 2l in good yields (Table 2, entry 12) under conven-
tional heating and MW irradiation.
The transesterification reaction was also realized in the
presence of the fatty diol [(12R,9Z)-octadecene-1,12-diol],
which is a derivative of ricinoleic acid. The diol was
obtained from the castor oil transesterification reaction
O
O
The reaction scope was investigated, performing the
synthesis of fatty acetoacetates 2a–k based on the natu-
ral availability of fatty acids derived from renewable
resources, i.e., saturated, unsaturated and polyunsaturated
fatty chains. The synthesis of 2a–k was performed under
the experimental conditions optimized to conventional
heating (30 mol% NH2SO3H, 6 h, 80 °C) and microwave
irradiation (30 mol% NH2SO3H, 13 min, 120 °C, 300 W).
The results are shown in Table 2.
OH
( )5
O
O
O
( )5
( )7
( )7
O
OH
major fatty acetoacetate
minor fatty acetoacetate
2m'
2m
Because slightly higher results were observed under
microwave irradiation, the consumption of starting materi-
als in short reaction times makes this method an efficient
approach to synthesize fatty compounds. In addition, the
fatty acetoacetates 2l and 2m derived from ricinoleic acid
Fig. 1 Fatty acetoacetates 2m and 2m′ and the selected region of
OH
( )5
O
NMR 1H (300 MHz, CDCl3)
OH
( )5
O
( )7
( )7
O
O
( )7
O
( )5
OH
castor oil
CH3OH, NaOH
60 °C, 90%
O
O
O
OH
( )5
O
CH3I, NaH
( )5
( )7
( )7
O
O
DMF
65%
12-OMe methyl
ricinoleate
methyl
ricinoleate
THF, Li(AlH4),
75%
O
O
O
O
O
O
OMe
( )5
( )5
( )7
2l
( )7
O
OH
NH2SO3H
80 oC or MW
1l
Fig. 2 Experiments of recycling of catalyst sulfamic acid in the
Scheme 3 Synthesis of fatty acetoacetate 2l derived from ricinoleic
transesterification reaction under MW irradiation
acid under conventional heating and MW irradiation in NH2SO3H
1 3

J Am Oil Chem Soc
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with subsequent reduction of methyl ricinoleate. However,
as expected, the transesterification reaction from diol and
methyl acetoacetate under conventional heating and MW
irradiation, which was catalyzed by sulfamic acid, led
to the formation of isomers 2m and 2m′ (2:1 mixture) as
1
observed in the selected region of the H-NMR spectrum
(Fig. 1).
Experiments of recycling of catalyst sulfamic acid were
performed. The reaction was carried out in the presence
of 30 mol% of sulfamic acid under microwave irradiation
(13 min, 120 °C, 300 W) using 1 g of palmitic alcohol (1f)
in a solvent-free medium. After completion of the reaction,
hexane was added and the filtered was separate of the sul-
famic acid. The recycled catalyst was used in further runs.
The 1st reuse resulted in a slightly diminishing of the yield.
However, no decrease in catalytic activity of sulfamic acid
was observed even after 2nd and 3rd reuses (Fig. 2).
9. Crespo A, El Maatougui A, Biagini P, Azuaje J, Coelho A, Brea
J, Loza MI, Cadavid MI, Garcia-Mera X, Gutierrez-de-Teran H,
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In conclusion, in this work, the synthesis of fatty acetoac-
etates from renewable resources was demonstrated under
sulfamic acid catalysis and solvent-free conditions using
MW irradiation. The products were isolated in good yields
(73–86 %) from transesterification process with long chain
alcohols in a few minutes using an eco-friendly approach,
which makes this method attractive over the existing meth-
ods for synthetically useful transesterification. In addition,
the catalytic activity of sulfamic acid is well maintained
after three cycles of catalysis.
Acknowledgments The authors are thankful for financial support
from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
(CAPES), Fundação de Apoio à Pesquisa do Estado do Rio Grande do
Sul (FAPERGS/PRONEM), and Conselho Nacional de Desenvolvi-
mento Científico e Tecnológico (CNPq). Fellowships from CAPES
(A. C. H. Weber) and CNPq (D. Russowsky and M. G. Montes
D’Oca) are also acknowledged.
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in Biginelli reaction under solvent-free, catalyst-free conditions.
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Compliance with ethical standards
Conflict of interest The authors declare no conflict of interests.
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1 3