Combining clays and ultrasound irradiation for an o-acetylation reaction of N-glucopyranosyl and other molecules

Article abstract of DOI:10.4067/S0717-97072014000300018

A convenient, efficient and fast acetylation combining clays and ultrasound irradiation is described. Some molecules from nature or synthetic source, i.e., D-glucose, glycerol, D-mannitol and 1,2,3-triazolic derivatives such as N-glucosyl sugars and 2-substituted 1,4-naphthoquinone structures were acetylated. This kind of chemistry may be classified as eco-friendly because the reactions take a short time and the catalyst is reusable.

Full text of DOI:10.4067/S0717-97072014000300018

J. Chil. Chem. Soc., 59, Nº 3 (2014)
COMBINING CLAYS AND ULTRASOUND IRRADIATION FOR AN O-ACETYLATION REACTION OF
N-GLUCOPYRANOSYL AND OTHER MOLECULES
RONALDO N. DE OLIVEIRA,* AUGUSTO DE L. XAVIER, BRUNA M. GUIMARÃES, VALENTINA N.
E MELO, WAGNER O. VALENÇA, WILSON S. DO NASCIMENTO, POLLYANNA L. F. DA COSTA AND
CELSO A. CAMARA
Departamento de Ciências Moleculares, Laboratório de Síntese de Compostos Bioativos, Universidade Federal Rural de Pernambuco,
Rua Dom Manoel de Medeiros S/N, Dois Irmãos, 52171-900, Recife, PE, Brazil.
ABSTRACT
A convenient, efficient and fast acetylation combining clays and ultrasound irradiation is described. Some molecules from nature or synthetic source, i.e.,
D-glucose, glycerol, D-mannitol and 1,2,3-triazolic derivatives such as N-glucosyl sugars and 2-substituted 1,4-naphthoquinone structures were acetylated. This
kind of chemistry may be classified as eco-friendly because the reactions take a short time and the catalyst is reusable.
Keywords: montmorillonites, carbohydrate, glycerol, acetylation, ultrasound.
literature procedure, and their analyses are comparable with reported data.13
INTRODUCTION
The compounds 5a, 5b and 2-amino-1,4-naphthoquinone are comparable with
reported data.18
The development of chemical building blocks inspired by nature is
commonly reported in scientific articles.1 Many natural and synthetic products
Typical experimental procedure for synthesis of N-glycosides (3a-d)
We employed the methodology adapted from literature.13 We only used
acetonitrile instead of the dichloromethane solvent.
have had their structures modified by chemical procedures. carboxylic esters
are considered very important functional groups in natural products and as
intermediates for organic synthesis. The pharmacological properties of some
molecules can be modified by a simple reaction of acetylation, a specific case
being the acetylation of salicylic acid (SA) to furnish acetyl salicylic acid
(ASA). In this context, one of the most used reactions is the acetylation of
alcohols. Recent works described various acetylating systems, for example
1’-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-4’-(3-hydroxypropyl)-
1H-1’,2’,3’-triazole (3a)
Solid; mp 160-162 °C; [a]D25= 50.0 (C=0.01/CH2CL2); 1H NMR (400 MHz,
CDCl3): d 7.68 (br s, 1H, Htriaz), 5.81 (d, 1H, J 7.6 Hz, H-1), 5.39-5.31 (m, 3H,
H-2, H-3, H-4), 4.29-4.21 (m, 1H, H-6a), 4.10 (br d, 1H, J 12.0 Hz H-6b), 3.98
(m, 1H, H-5), 3.65 (t, 2H, CH2), 3.07 (t, 2H, CH ), 2.85 (t, 2H, CH ), 2.02 (s,
3H, CH3CO), 2.00 (s, 3H, CH3CO), 1.96 (s, 3H, C2H3CO), 1.82 (s, 3H2, CH3CO).
13C NMR (100 MHz, CDCl ): δ 170.5, 169.3, 169.1, 169.0, 128.0, 110.0, 86.3,
75.3, 70.8, 72.5, 70.4, 67.6, 361.5, 31.5, 27.9, 21.7, 20.7, 20.5, 20.2, 20.1. Anal.
Calc.: C19H27N3O10: C, 49.89; H, 5.95. Found: C, 50.02; H, 5.89.
2
3
with Ph3P(OAc)2, triethyl orthoacetate, vinyl acetate-I2,4 acetyl chloride or
Ac2O-DMAP-py. 5 In addition, clays are frequently employed as heterogeneous
6,7
systems to promote acetylation reaction.
Specifically, the acylation of
alcohols has been carried out using montmorillonite K10 impregnated with
some metals, such as FeCl3,6 InCl3,8 and Cu2+,9 among others.10
Introduction of new laboratory techniques is noteworthy exciting for
the undergraduate students involved in organic chemistry experiments. One
fast-growing area is organic synthesis using an ultrasound irradiation bath.11
(±)-1’-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-4’-(2-
hydroxypropyl)-1H-1’,2’,3’-triazole (3b)
Our research group has been using the ultrasonic technique for the synthesis
13
of amidoximes,12 carbohydrates
and 1,2,3-triazole derivatives via click
1
Solid; mp 170-172 °C; [a] 25= -80.0 (C= 0.01/CH2CL ); H NMR (400
chemistry.14 However, there are only a few examples reported in the literature
thatcombineclaysandultrasoundenergy15 andonlyoneexamplefor acetylation
using this technique.16 In general, this kind of chemistry is considered eco-
friendly because these procedures are known for their efficiency, short reaction
time and easily removable and reusable catalyst.
MHz, CDCl3): d 7.75 (br s, 1H,DHtriaz), 5.87 (br s, 1H, H-1), 25.46-5.22 (m, 3H,
H-2, H-3, H-4), 4.34-4.15 (m, 3H, H-6a, H-6b, CHO), 4.09 (m, 1H, H-5), 2.93-
2.76 (m, 3H, OH, CH2), 2.09 (s, 3H, CH3CO), 2.07 (s, 3H, CH3CO), 2.03 (s, 3H,
CH3CO), 1.88 (s, 3H, CH3CO). 13C NMR (100 MHz, CDCl3): δ 170.5, 169.9,
169.3, 169.0, 120.6, 144.7, 86.3, 75.3, 72.3, 70.7, 67.7, 61.5, 34.6, 34.4, 22.9,
20.7, 20.5, 20.4, 20.2. Anal. Calc.: C19H27N3O10: C, 49.89; H, 5.95. Found: C,
49.66; H, 6.05.
After started our studies,17 we decided to prepare a diversity of acetylated
molecules of natural or synthetic origin using clays (montmorillonite K10 or
KSF), acetic anhydride and ultrasonic energy.
(±)-1’-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-4’-(1-
hydroxyethyl)-1H-1’,2’,3’-triazole (3c)
EXPERIMENTAL
1
Solid; mp 193-195 °C; [a] 25= -16.5 (C=0.01/CH2CL ); H NMR (400
MHz, CDCl3): 7.73 (s, 1H, Htriaz), D5.87 (d, 1H, J 8.8 Hz, H-1),25.43-5.24 (m, 3H,
H-2, H-3, H-4), 5.07 (q, J 6.0 Hz, CHO), 4.30 (dd, 1H, J 5.2, 12.4 Hz, H-6a),
4.15 (br d, 1H, J 12.4 Hz, H-6b), 4.01 (m, 1H, H-5), 2.08 (s, 3H, CH3CO), 2.07
(s, 3H, CH3CO), 2.03 (s, 3H, CH3CO), 1.88 (s, 3H, CH3CO), 1.60 (br d, 3H, J
6.8 Hz, CH ). 13C NMR (100 MHz, CDCl3): δ 170.5, 169.9, 169.3, 168.9, 153.1,
118.6, 85.73, 75.1, 72.6, 70.3, 67.7, 63.1, 63.0, 61.5, 23.0, 22.9, 20.6, 20.5, 20.1.
Anal. Calc.: C18H25N3O10: C, 48.76; H, 5.68. Found: C, 48.50; H, 6.01.
General
All organic solvents were analytical grade (Vetec-Brazil). All reactions
were monitored by TLC analysis containing GF-254 (Merck-Darmstadt,
Germany). The clays (montmorillonite K10 and KSF) were purchased from
Aldrich. Reactions were carried out in a USC-1400A Ultracleaner ultrasound
cleaning bath with an operating frequency of 40 kHz. Column chromatography
was performed on Merck silica gel 60, optical rotations were measured using an
Anton-Paar MCP 200 polarimeter and values are given in deg.cm2, g-1; Melting
points were determined in a PFM II BioSan apparatus and are uncorrected. 1H
(400 MHz), 13C NMR (100 MHz) spectra were obtained in Varian Unity Plus
at 400 spectrometers in CDCl3. Elemental analyses were carried out in a CA
EA1110 CHNS-O analyzer. GC-MS (60-240 ºC at 3 º C min rates) on a Varian
431-GC device coupled to a Varian 220-MS instrument using a fused-silica
capillary column (30 m × 0.25 mm i.d. × 0.25 μm) coated with DB-5. MS
spectra were obtained using EI mode at 70 eV, at scan intervals of 0.5 s and
fragments from 40 to 550 Da. The compounds 1 and 2 were synthesized using
1’-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-4’-(1-
hydroxycyclohexyl)-1H-1’,2’,3’-triazole (3d)
Solid; mp 175-179 °C; [a] D25= -3.8 (C=0.01/CH2CL2) 1H NMR (400 MHz,
CDCl3): 7.70 (s, 1H, Htriaz), 5.85 (d, 1H, J 8.8 Hz, H-1), 5.43, 5.23 (m, 3H, H-2,
H-3, H-4), 4.30 (dd, 1H, J 5.2, 12.4 Hz, H-6a), 4.15 (br d, 1H, J 12.4 Hz, H-6b),
4.00 (m, 1H, H-5), 2.08 (s, 3H, CH3CO), 2.06 (s, 3H, CH3CO), 2.02 (s, 3H,
CH3CO), 1.85 (s, 3H, CH3CO), 1.80-1.25 (m, 10H, cyclohexyl). 13C NMR (100
MHz, CDCl3): δ 170.5, 169.9, 169.3, 168.8, 145.1, 118.2, 85.8, 75.1, 72.6, 70.3,
e-mail: ronaldonoliveira@dcm.ufrpe.br
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J. Chil. Chem. Soc., 59, Nº 3 (2014)
69.5, 67.8, 61.6, 38.0, 25.3, 21.9, 20.5, 20.1 Anal. Calc.: C22H31N3O10: C, 53.11;
H, 6.28. Found: C, 52.83; H, 6.46.
2-[4-(1-O-acetyl-1-methyl-ethyl)-1H-1,2,3-triazol-1-yl)]-1,4-
naphtoquinone (7)
Typical experimental procedure for synthesis of acetylated compounds
An intimate mixture of hydroxyl compounds (1 mmol) and clay (200
% weight/substrate) were well mixed individually and placed in a 125 mL
erlenmeyer followed by the addition of acetic anhydride (4 equiv/OH). The
mixture was irradiated in an ultrasonic bath at the indicated temperature for a
specific time. The completion of the reaction was verified by use of thin-layer
chromatography (TLC). After this, 10 mL de ethyl acetate was added and the
crude material was filtered and the resulting organic phase was washed with
water and a NaHCO3 saturated solution and dried with anhydrous sodium sulfate.
Then, column chromatography with gradient ethyl acetate/n-hexane was used
to generate the desired pure products. We have tested to scale-up the present
method at 25 mmol scale to obtain comparable results for the compounds 1 and
10.
Solid; mp 165-166 °C; 1H NMR (400 MHz, CDCl ): δ 8.61 (s, 1H, Htriaz),
8.21-8.15 (m, 2H, Hnaphth), 7.87-7.84 (m, 2H, Hnaphth), 7.377 (s, 1H, Hnaphth), 2.03
(s, 3H, OAc), 1.92 (s, 6H, CH3). 13C NMR (100 MHz, CDCl3): δ 183.8, 179.3,
170, 152.6, 139.3, 135, 134.4, 131.4, 127.2, 126.5, 123.2, 76.3, 27.3, 22.2. Anal.
Calc.: C17H15N3O4 x 0.3 H2O: C, 61.72; H, 4.77. Found: C, 61.72; H, 4.33.
2-[4-(prop-1-en-2-yl)-1H-1,2,3-triazol-1-yl)]-1,4-naphtoquinone (8)
Solid; mp 137-139 °C; 1H NMR (400 MHz, CDCl3): δ 8.53 (s, 1H, H
),
8.16-8.09 (m, 2H, Hnaphth), 7.81-7.76 (m, 2H, Hnaphth), 7.71 (s, 1H, Htriaz),na5ph.t8h5
(s, 1H, C=CH) 5.16 (s, 1H, C=CH), 2.13 (s, 3H, CH3). 13C NMR (100 MHz,
CDCl3): δ 183.1, 178.9, 149.1, 138.6, 134.4, 133.7, 131.9, 130.9, 126.6, 125.9,
125.5, 120.8, 113.5, 19.9. Anal. Calc.: C15H11N3O2: C, 67.92; H, 4.18. Found:
C, 67.88; H, 4.33.
1’-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-4’-(3-O-acetyl-propyl)-
1H-1’,2’,3’-triazole (4a)
RESULTS AND DISCUSSION
Solid; mp 143-145 °C; [a] D25= -40.0 (C=0.01/CH2CL2); 1H NMR (400 MHz,
CDCl3): d 7.56 (s, 1H, H ), 5.85 (d, 1H, J 9.0 Hz, H-1), 5.42-5.23 (m, 3H, H-2,
H-3, H-4), 4.30 (dd, 1H,trJiaz12.5, 7.4 Hz, H-6a), 4.14 (br d, 1H, J 12.5 Hz, H-6b),
4.10 (t, 2H, J 6.3 Hz, CH2O), 4.01-3.98 (br dd, 1H, 1H, J 10.1, 3.0 Hz, H-5), 2.81
(t, 2H, J 7.5 Hz, CH2), 2.08 (s, 3H, CH3CO), 2.06 (s, 3H, CH3CO), 2.05 (s, 3H,
CH3CO), 2.02-199 (m, 5H, CH2, CH CO), 1.87 (s, 3H, CH3CO). 13C NMR (100
MHz, CDCl3): δ 171.1, 170.5, 169.9,3169.4, 169.0, 147.7, 119.2, 85.7, 75.1, 72.6,
70.2, 67.7, 63.3, 61.5, 28.0, 22.4, 22.1, 20.7, 20.1. Anal. Calc.: C21H29N3O11: C,
50.50; H, 5.85. Found: C, 50.45; H, 5.93.
Protection and deprotection of hydroxyl groups in chemistry has been a
tool commonly used in carbohydrate chemistry. To begin our studies we chose
the carbohydrate D-glucose for acetylation (Scheme 1). First, we used mont.
K10 and Ac2O in an ultrasound bath in the absence of a solvent. We differed
the amount of mont. K10 from 20 to 200 % (w/w), acetic anhydride (1 to 4
equiv/OH), and reaction time (15 or 30 min). Then, was determined the best
condition, i.e., mont. 200%, 4 equiv of Ac2O per hydroxyl group, and 15 min
under ultrasound irradiation at room temperature.
After that, was exchanged mont. K10 to KSF and the yields of reactions
were very close, 92% and 94%, respectively. The stereoselectivity at the
anomeric carbon showed a ratio α:β of 3:1 with KSF, while for K10 the ratio
was 3:2. We also obtained best results when montmorillonite K10 without
activation was tested, which reacted with a complete conversion for acetylated
products. However, when clay was used after the activation process, the
reaction was not complete. Apparently, the presence of water inside the cage-
like structure or channels in the clay enhanced the acoustic cavitations in this
reaction. Another aspect this reaction is the difference between anhydride and
monohydrated D-glucose, which has the best results for anhydride glucose,
since it was necessary to add 20 equiv Ac O more to complete the reaction
when monohydrated D-glucose was used. 2In this case, probably molecular
water hydrolyzes the anhydride and consequently causes loss of their reactivity.
Nevertheless, in regard to stereoselectivity, significant difference was not found.
(±)-1’-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-4’-(2-O-acetyl-
propyl)-1H-1’,2’,3’-triazole (4b)
1
Solid; mp 117-119 °C; [a] 25= -13.2 (C=0.007/CH2CL ); H NMR (400
MHz, CDCl ): d 7.59 (s, 1H, HtriaDz), 5.85 (dd, 1H, J 9.0 Hz, H2-1), 5.45-5.22 (m,
3H, H-2, H-33, H-4), 5.15 (m, 1H, CHO), 4.32 (dd, 1H, J 12.0, 4.7 Hz, H-6a),
4.16 (dd, 1H, J 12.0, 2.0 Hz, H-6b), 4.00 (ddd, 1H, J 10.2, 4.7, 2.0 Hz, H-5),
2.96-2.89 (m, 2H, CH O), 2.09 (s, 3H, CH3CO), 2.07 (s, 3H, CH CO), 2.03 (s,
3H, CH3CO), 2.06 (s, 32 H, CH3CO), 1.87 (2 s, 3H, CH3CO, R and3S), 1.28-1.25
(2 d, 3H, J 6.3, 6.3 Hz, CH3, R and S). 13C NMR (100 MHz, CDCl , R and S): δ
170.4 (2C), 169.8, 169.4, 168.9, 144.5, 120.1, 86.0 and 85.8, 75.2 a3nd 75.0, 73.1
and 72.6, 70.2, 69.8 and 68.5, 67.7 and 67.6, 61.5, 32.1, 21.2 (2C, R and S), 20.7,
20.5 (2C, R and S), 20.5, 20.1 and 20.0 (R and S), 19.6 and 19.4 (R and S). Anal.
Calc.: C21H29N3O11: C, 50.50; H, 5.85. Found: C, 50.62; H, 5.83.
(±)-1’-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-4’-(1-O-acetyl-
ethyl)-1H-1’,2’,3’-triazole (4c)
1
Solid; mp 164-166 °C; [a] 25= -35.3 (C=0.002/CH CL2); H NMR (400
MHz, CDCl3): d 7.79 (s, 1H, Htriaz), 6.05 (m, 1H, CHO), 52.87 (2 d, R and S, 1H,
J 8.6 Hz, H-1), 5.46-5.22 (m, 3H, H-2, H-3, H-4), 4.32 (dd, 1H, J 12.7, 5.1 Hz,
H-6a), 4.16 (br d, 1H, J 12.7 Hz, H-6 ), 4.01 (ddd, 1H, J 10.2, 4.7, 2.0 Hz, H-5),
2.10 (s, 3H, CH3CO), 2.08 (s, 3H, CbH3CO), 2.07 (s, 3H, CH3CO), 2.03 (s, 3H,
CH3CO), 1.87 (s, 3H, CH3CO), 1.68 (d, 3H, J 5.5 Hz, CH ). 13C NMR (100 MHz,
CDCl3, R and S): δ 170.5, 170.2, 169.9, 169.3, 168.7, 1346.0, 106.9, 85.8, 75.2,
72.7 and 72.6, 70.3 and 70.2, 67.7, 64.8 and 64.7, 61.5, 29.7, 21.2 (2C, R and
S), 20.7, 20.5, 20.4, 20.1, 19.6 and 19.3 (R and S). Anal. Calc.: C20H27N3O11: C,
49.48; H, 5.61. Found: C, 49.25; H, 5.40.
D
Scheme 1. Acetylation of D-glucose using US and clay conditions
In order to analyze the reusability of the K10 and KSF clays, the catalyst
was recovered at the end of the reaction and its recycling use was evaluated
immediately after the first reaction. The solid acid was removed by filtration
and washed with ethyl acetate. The catalyst lost its activity after four reuses (<
70 %, see Fig. 1). Each time, the recovered catalyst was found to be reusable
and showed a range of yields from 92% to 50% after seven catalytic cycles
using K10. The results for KSF were close, as shown in Figure 1.
1’-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-4’-(1-O-acetyl-
cyclohexyl)-1H-1’,2’,3’-triazole (4d)
Solid; mp 148-150 °C; [a] 25= -7.0 (C=0.001/CH2CL ); 1H NMR (400
MHz, CDCl ): 7.72 (s, 1H, Htriaz), D5.86 (d, 1H, J 8.6 Hz, H-1),25.48-5.22 (m, 3H,
H-2, H-3, H3-4), 4.32 (dd, 1H, J 4.7, 12.5 Hz, H-6a), 4.15 (br d, 1H, J 12.5 Hz,
H-6b), 4.02 (m, 1H, H-5), 2.40-2.36 (m, 4H, 2 CH2, cyclohexyl), 2.03 (s, 3H,
CH3CO), 2.00 (s, 3H, CH3CO), 1.96 (s, 3H, CH3CO), 1.92 (s, 3H, CH3CO), 1.81
(s, 3H, CH3CO), 1.79-1.32 (m, 6H, cyclohexyl). 13C NMR (100 MHz, CDCl3):
δ 170.5, 169.9 (2C), 169.3, 168.9, 157.1, 120.3, 85.6, 76.5, 75.2, 72.7, 67.8,
61.6, 35.7, 34.7, 29.7, 25.2, 22.0, 22.0, 21.8, 20.5, 20.0, 18.2, 16.6. Anal. Calc.:
C24H33N3O11: C, 53.43; H, 6.17. Found: C, 53.53; H, 6.20.
To continue our studies, we selected mont. K10 clay as the standard catalyst
for our acetylation procedure. We focused our attention on molecules such
as N-glucosyl triazolic sugars, glycerol, D-mannitol and some 2-substituted
1,4-naftoquinone structures.
For the synthesis of N-glucosyl triazolic alcohols, we started from the
per-O-acetilated glucose 1 via azide sugar 2, using the click triazole synthesis
methodology based on ultrasonic energy developed in our laboratory.13 Then,
the triazolic sugars 3a-d were obtained in 10-40 min with yields between 60
and 98 % (Scheme 2, Table 1).
The acetylation step, using our optimized protocol (Ac2O/K10/US/rt),
produced acetylated compounds 4a-d in moderate to good yields of 47-73
% (Scheme 2, Table 1). The N-glucopyranoside was compatible with these
reaction conditions without hydrolysis. Only in one case the starting material
was recovered (Entry 2, Table 1). In all cases, no elimination products were
detected.
2-[4-(O-acetyl-methyl)-1H-1,2,3-triazol-1-yl)]-1,4-naphtoquinone (6)
1
Solid; mp 150-152 °C; H NMR (400 MHz, CDCl ): δ 8.70 (s, 1H, Htriaz),
8.23-8.20 (m, 2H, Hnaphth), 7.86-7.84 (m, 2H, Hnaphth), 7.375 (s, 1H, Hnaphth), 5.31
(s, 2H, CH ), 2.11 (m, 3H, OAc). 13C NMR (100 MHz, CDCl ): δ 183, 178.5,
170.1, 143.23, 138.5, 134.4, 133.8, 130.8, 126.6, 126.2, 125.9, 1325.4, 56.6, 20.2.
Anal. Calc.: C15H11N3O4x0.3 H2O: C, 59.51; H, 3.87; N, 13.88. Found: C, 59.70;
H, 3.55.
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J. Chil. Chem. Soc., 59, Nº 3 (2014)
Scheme 2. Synthesis of N-glucosyl triazolic 3a-d and 4a-d using US and
clay conditions
Figure 1. Reusability of K10 and KSF from D-glucose acetylation reaction
Table 1. Synthesis of the compounds 3a-d and 4a-d using US and clay conditions.
Yields, % a
(Time, min)
Time
(min)
Entry
Alcohol
Acetylated Products
Yields, % a
AcO
AcO
O
N
N
N
1
3a
93 (30)
4a
60
58
OAc
AcO
OAc
AcO
AcO
O
N
N
OAc
2
3b
3c
97 (20)
98 (10)
4b
4c
N
30
30
47 b
AcO
OAc
AcO
O
N
N
AcO
N
3
73
OAc
OAc
AcO
OAc
AcO
AcO
O
N
N
N
4
3d
60 (40)
4d
30
58
AcO
OAc
a After column chromatography; b Recovered starting materials.
To prepare derivates containing the 1,4-naphtoquinone moiety, we started
from 2-[4-hydroxymethyl-1H-1,2,3-triazol-1-yl)-1,4-naphthoquinone 5a and
2-[4-(2-hydroxy1-2-methyl-ethyl-)-1H-1,2,3-triazol-1-yl]-1,4-naphthoquinone
5b, that were synthesized using a method recently described by us.18 The
min. From the compound 5b, after a reaction time of 40 min, the product 7 was
obtained in 58 %, and the by-product 8 was isolated in yields of 37% as a vinyl
derivative due to their dehydration. Normally, these alkenyl type compounds
may be prepared from dehydration of tertiary alcohol linked to a 1,2,3-triazole
function using POCl3/HCl.19 Additionally, this mild condition was not efficient
in promoting acetylation of 2-amino-1,4-naphthoquinone, which is expected
for this kind of of extensive conjugated molecule, which requires harsher
conditions (RCOCl/NaH).20
o
acetylation reaction was performed at 50 C during 40 min with some drops
of dichloromethane added to facilitate solubility. The acetylated compound 6
was obtained in yields of 77 % after column chromatography (Scheme 3). At
room temperature, the results were similar; however, the reaction time takes 60
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J. Chil. Chem. Soc., 59, Nº 3 (2014)
a possible nucleophilic attack from a carbonyl group to eliminate acetic acid
and forming the cyclic structure B (pathway-a). Another pathway is the loss of
radical AcO× leading to structure B’ m/z 159 (pathway-b). The third possibility
from structure A is the elimination of the radical AcOCH2× to form structure
C m/z 145 (pathway-c). To rationalize the peak m/z 103 (structure D), we
assumed initially an intramolecular hydrogen transfer and then loss of ketene
(O=C=CH2). The acylium ion m/z 43 was formed mainly from [M]+∙ after loss
of the radical AcOCH2CH(OAc)CH2O×. We also proposed fragmentation from
ion m/z 103 to form m/z 43 and ethylene diol, as depicted in Scheme 6.
Scheme 3. Synthesis of 2-substituted 1,4-naftoquinones 6-8 using US and
clay conditions
After that, we tried the exclusive preparation of 8; however, without
success from 5b using acid conditions (HCl, H2SO , AcOH). On the other hand,
when we employed AcOH/reflux from acetylated4compound 7, the compound
8 was formed (Scheme 3). Then, we conclude that by-product 8 only could
be obtained from 7. We have found in the literature results that can explain
this effect.21 Delatouche and co-workers21 describes mildly acid conditions
to furnish amine derivatives and conjugated alkene from triazolylcarbamates
as leaving group. Based on this information we proposed an elimination
mechanism. First, a complex between K10 and carbonyl group was formed,
which after triazole protonation at N3 the conjugated base (AcO-) may be
remove a proton at methyl position to form 8 and acetic acid (Scheme 4), an
assisted version of a classical E2 mechanism.
Scheme 4. Proposed elimination mechanism for the formation of alkene 8
Scheme 6. Proposed fragmentation for tri-acetylglycerol 9
In the next step, we investigated the preparation of triacetil derivative
9 (Scheme 5-I). This compound is able to be produced in an acid-catalyzed
reaction of glycerol with acetic anhydride.22 The tri-acetylglycerol 9 was
synthesized in yields of 55 % employing montmorillonite K10 as the catalyst.
On the other hand, when KSF was employed, the yield was higher at 79%. This
result may be rationalized according to literature that describes KSF as more
efficient than K10 because of its higher acidic character.23
Hexa-O-acetyl-D-mannitol 10 has received attention recently from the
scientific community.25,26 We acetylated D-mannitol using K10 or KSF to
furnish hexa-O-acetyl-D-mannitol 10 in yields of 67% and 70 %, respectively
(Scheme 5-II). The H NMR analysis showed the proton shift and coupling
constant expected for this compound.
1
CONCLUSION
In this work, we revisited a versatile methodology for the acetylation
reaction of important molecules that have a diversity of applications. For
this purpose, we have combined clays (montmorillonite K10 or KSF) and
ultrasound energy to explore the acetylation reaction on natural or synthetic
compounds such as D-glucose, D-mannitol, glycerol and 1,2,3-triazolic
derivatives, i.e., N-glucopyranosyl sugars and 2-substutated 1,4-naftoquinoid
structures. The acetylated products were obtained in moderate to good yields.
This is a faster, eco-friendly and remarkable procedure for prompt use in the
formation of acetyl derivatives of alcohols in laboratory.
ACKNOWLEDGEMENTS
Scheme 5. Synthesis of tri-acetylglycerol 9 and hexa-O-acetyl-D-mannitol
10 using US and clay conditions
The authors are grateful to FACEPE-PRONEM (1232.1.06/10) for financial
support. W. S. Nascimento and P. L. F. Costa are gratefully to FACEPE and
V. N. e Melo to CAPES for providing a fellowship. Our thanks are also due
to Analytical Centers CENAPESQ-UFRPE for facilities installation and DQF-
UFPE for obtaining the spectral data.
The literature describes the use of EI-MS (70 eV) for analysis of
triacetylated glycerol showing the peaks m/z 218, 145 (M- CH2OAc), 103
(100%) and 43 as main ions.24 In our study, the analysis of the CG-MS showed
fragmentation expected for 9 (Scheme 6). Nevertheless, our CG-MS spectrum
did not show the molecular ion [M]+∙. We observed the peak at 159 (M-AcOH)
with 100% relative abundance, as shown in Figure 2. To explained the ion
m/z 159, we are suggesting that after the molecular ion [M]+∙ is formed, there
immediately occurs a 1,2-H rearrangement to obtain the structure A (Scheme
5). From structure A we proposed three pathways for fragmentation. Firstly,
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