Synthesis of novel glycerol-fluorinated triazole derivatives and evaluation of their phytotoxic and cytogenotoxic activities

Abstract

The control of weeds in agriculture is mainly conducted with the use of synthetic herbicides. However, environmental and human health concerns and increased resistance of weeds to existing herbicides have increased the pressure on researchers to find new active ingredients for weed control which present low toxicity to non-target organisms, are environmentally safe, and can be applied at low concentrations. It is herein described the synthesis of glycerol-fluorinated triazole derivatives and evaluation of their phytotoxic and cytogenotoxic activities. Starting from glycerol, ten fluorinated triazole derivatives were prepared in four steps. The assessment of them on Lactuca sativa revealed that they present effects on phytotoxic and cytogenotoxic parameters with different degrees of efficiency. The compounds 4a, 4b, 4d, 4e, 4i, and 4j have pre-emergent inhibition behavior, while all the investigated compounds showed post emergent effect. Mechanism of action as clastogenic, aneugenic, and epigenetic were observed in the lettuce root meristematic cells, with alterations as stick chromosome, bridge, delay, c-metaphase, and loss. It is believed that glycerol-fluorinated triazole derivatives possess a scaffold that can be explored towards the development of new chemicals for the control of weed species.

Full text

An Acad Bras Cienc (2023) 95(1): e20211102 DOI 10.1590/0001-3765202320211102
Anais da Academia Brasileira de Ciências | Annals of the Brazilian Academy of Sciences
Printed ISSN 0001-3765 I Online ISSN 1678-2690
www.scielo.br/aabc | www.fb.com/aabcjournal
An Acad Bras Cienc (2023) 95(1)
Running title: Synthesis and
biological eect of new triazoles
Academy Section: CHEMICAL
SCIENCES
e20211102
95
(1)
95(1)
DOI
10.1590/0001-3765202320211102
CHEMICAL SCIENCES
Synthesis of novel glycerol-fluorinated
triazole derivatives and evaluation of their
phytotoxic and cytogenotoxic activities
FERNANDO F. BARCELOS, THAMMYRES A. ALVES, POLIANA A.R. GAZOLLA,
RÓBSON RICARDO TEIXEIRA, VAGNER T. DE QUEIROZ, MILENE M. PRAÇA-FONTES,
PEDRO A.B. MORAIS, VICTOR R. FONSECA, WANDERSON ROMÃO, VALDEMAR
LACERDA JÚNIOR, RODRIGO SCHERER & ADILSON V. COSTA
Abstract: The control of weeds in agriculture is mainly conducted with the use of
synthetic herbicides. However, environmental and human health concerns and increased
resistance of weeds to existing herbicides have increased the pressure on researchers
to find new active ingredients for weed control which present low toxicity to non-target
organisms, are environmentally safe, and can be applied at low concentrations. It is
herein described the synthesis of glycerol-fluorinated triazole derivatives and evaluation
of their phytotoxic and cytogenotoxic activities. Starting from glycerol, ten fluorinated
triazole derivatives were prepared in four steps. The assessment of them on Lactuca
sativa revealed that they present effects on phytotoxic and cytogenotoxic parameters
with different degrees of efficiency. The compounds 4a, 4b, 4d, 4e, 4i, and 4j have
pre-emergent inhibition behavior, while all the investigated compounds showed post
emergent effect. Mechanism of action as clastogenic, aneugenic, and epigenetic were
observed in the lettuce root meristematic cells, with alterations as stick chromosome,
bridge, delay, c-metaphase, and loss. It is believed that glycerol-fluorinated triazole
derivatives possess a scaffold that can be explored towards the development of new
chemicals for the control of weed species.
Key words: 1,2,3-triazole, cytotoxicity, fluorinated derivatives, glycerol, phytotoxicity.
INTRODUCTION
The use of herbicides for weed control is an
important tool in modern agriculture because
chemical control is fast, efficient, and cost
effective. However, indiscriminate use of the
same herbicide exerts high selection pressure
on weed populations, which thus promotes the
selection of biotypes resistant to these products
(Han et al. 2021, Alves et al. 2021).
Based on the importance of herbicides, since
the discovery of dichlorodiphenyltrichloroethane
(DDT) in 1939, the agrochemical industry has
been constantly developing successful new
methodologies of organic synthesis with the
objective of providing increasingly selective,
efficient and environmentally safe compounds.
Currently, more than 1.200 agrochemicals are
known and many of them are regularly used by
farmers to generate the food supply to support
the expanding global population.
In the last two decades, fluorochemicals
have been associated with significant advances
in the agrochemical development process
(Ogawa et al. 2020). Among the herbicides
licensed worldwide, currently around 25%
contain at least one fluorine atom and several

FERNANDO F. BARCELOS et al. SYNTHESIS AND BIOLOGICAL EFFECT OF NEW TRIAZOLES
An Acad Bras Cienc (2023) 95(1) e20211102 2 | 15
contain multiple fluorines in the form of
difluoro and trifluoromethyl groups. Over the
years, the use of halogens in the design of
new agrochemicals has substantially increased
as well as the presence of these atoms in the
active ingredients of new commercial products.
Jeschke stated “the introduction of halogens
into active ingredients has become an important
concept in the quest for a modern agrochemical
with optimal efficacy, environmental safety, user
friendliness, and economic viability” (Jeschke
2010). Taking fluorine into consideration, its
van der Waals radius is similar to hydrogen. It
can mimic hydrogen atoms or hydroxyl groups
in bioactive compounds. Such modifications
(substitution of an H or OH by a fluorine) can
result, for example, in improved selectivity.
Moreover, because of the high electronegativity
associated with fluorine, the introduction of
this atom in a molecule creates a high dipole
moment and can alter the acidity of functional
groups. Lipophilicity of compounds is another
property that can be altered by the introduction
of fluorine atoms. These features (among others)
(Jeschke 2004) related to the introduction of
fluorine atoms in compounds can result in
changes in the physicochemical properties
of the molecules which, in turn, can result in
improved biological responses (Andrade-Vieira
et al. 2012).
Fluorine-containing compounds have made
a significant contribution to the development
of products for the agrochemicals industry and
many organofluorine entities have found stable
market positions (Fujiwara & Hagan 2014).
Another class of organic compounds
widely employed as pharmaceuticals and
agrochemicals is the nitrogen containing
heterocyclic compounds. Considering the
heterocyclic systems, 1,2,3-triazoles hold great
importance due to their broad spectrum of
applications in pharmaceuticals, biochemical,
medicinal, material sciences, and agrochemical
(Avulaa et al. 2019). Their chemistry underwent
a substantial growth over the past decades.
1H-1,2,3-triazole containing compounds were
reported to exhibit a large range of biological
activities such as fungicide, phytotoxic and
cytogenotoxic (Costa et al. 2017, 2020).
Considering the importance of heterocyclic
compounds containing nitrogen and fluoro-
chemicals in the development of new
agrochemicals and as well as our interest in the
chemistry of triazoles and in the preparation of
bioactive compounds that can be used as new
active ingredients to control weeds, it is herein
described the synthesis of novel 1,2,3-triazoles
bearing fluorinated aryl moieties and evaluation
of their phytotoxic and cytogenotoxic activities.
MATERIALS AND METHODS
Generalities
The solvents and reagents with high purity were
purchased from Vetec (Rio de Janeiro, Brazil),
except the terminal alkynes that were procured
from Sigma-Aldrich (St. Louis, MO, USA), and
used as received from the commercial suppliers.
The reaction progress was monitored by thin
layer chromatography (TLC). Analytical thin layer
chromatography analysis was conducted on
aluminum backed precoated silica gel plates
using different solvent systems. TLC plates
were visualized using potassium permanganate
solution, phosphomolybdic acid solution,
and/or UV light. Column chromatography was
performed using silica gel 60 (60-230 mesh). The
IR spectra were acquired using a Tensor 27 device
and the attenuated total reflection technique
(Bruker, Karlsruhe, Germany) scanning from 500
to 4000 cm-1. The 1H and 13C NMR spectra were
recorded on a Varian Mercury 400 instrument
(Varian, Palo Alto, CA, USA), at 400 MHz for 1H
and 100 MHz for 13C, using CDCl3 as deuterated

FERNANDO F. BARCELOS et al. SYNTHESIS AND BIOLOGICAL EFFECT OF NEW TRIAZOLES
An Acad Bras Cienc (2023) 95(1) e20211102 3 | 15
solvent and TMS as internal standard. Mass
spectra were recorded on a GCMS-QPPlus 2010
device (Shimadzu, Kyoto, Japan) under electron
impact (70 eV) conditions of positive ion mode.
Melting points were determined with MA 381
equipment (Marconi, São Paulo, Brazil) and are
uncorrected.
The 1H NMR data are presented as follows:
chemical shift (δ) in ppm, multiplicity, the
number of hydrogens, and J values in Hertz (Hz).
Multiplicities are indicated by the following
abbreviations: s (singlet), d (doublet), dap
(apparent doublet), dd (doublet of doublets),
td (triplet of doublets), tdd (triplet of doublet
of doublets), t (triplet), tap (apparent triplet), tt
(triplet of triplets), quartet, and m (multiplet).
Synthetic procedures
Preparation of compounds 1, 2, and 3
The intermediate compounds (2,2-dimethyl-
1,3-dioxolan-4-yl) methanol (1), (2,2-dimethyl-
1,3-dioxolan-4-yl)methyl-4-methyl
benzenesulfonate (2), and 4-(azidomethyl)-2,2-
dimethyl-1,3-dioxolane (3) were synthesized as
previously reported in the literature (Costa et al.
2017, 2020).
General procedure for the synthesis of glycerol-
fluorinated triazole derivatives 4a-4k
The azide 3 (1.50 equivalent), terminal alkyne (1.00
equivalent), aqueous solution of CuSO45H2O
(0.100 mol L–1, 1.00 mL, 0.0960 mmol), sodium
ascorbate (0.0600 g, 0.288 mmol) and aqueous
solution of tert-butyl alcohol (1:1 v v-1, 12.0 mL)
were added to a round-bottomed flask. The
resulting reaction mixture was stirred at 50 °C
for 8 h. After the completion of the reaction,
as verified by TLC analysis, distilled water (10.0
mL) was added and the aqueous phase was
extracted with dichloromethane (3 × 20 mL).
The organic extracts were combined, and the
resulting organic layer was dried over anhydrous
sodium sulfate, filtered, and concentrated under
reduced pressure. The crude products were
purified by silica gel column chromatography
eluting with ethyl acetate-methanol (9:1 v v-1). The
structures of compounds 4a-4k are supported
by the following data.
Synthesis of 1-((2,2-dimethyl-1,3-dioxolan-4-
yl)methyl)-4-phenyl-1H-1,2,3-triazole (4a)
White solid, prepared in 83% yield from the
reaction between phenylacetylene (1.50 g, 14.7
mmol) and azide 3 (1.50 g, 9.60 mmol), m.p.120-
123 °C. TLC: Rf = 0.57 (ether-dichloromethane, 10:1
v v-1). IR (ATR) /cm-1: 3145, 2992, 2923, 2853, 1607,
1484, 1461, 1438, 1373, 1262, 1224, 1202, 1166, 1115,
1063, 1041, 970, 883, 833, 767, 699. 1H NMR (400
MHz, CDCl3) δ: 1.32 (s, 3H), 1.36 (s, 3H), 3.74 (dd,
1H, J1 = 8.8 Hz and J2 = 6.0 Hz), 4.09 (dd, 1H, J1
= 8.8 Hz and J2 = 6.4 Hz), 4.40-4.50 (m, 2H), 4.55
(dd, 1H, J1 = 12.8 Hz and J2 = 2.8), 7.29 (tt, 1H, J1 =
8.0 Hz and J2 = 1.2 Hz), 7.37-7.41 (m, 2H), 7.80 (dd,
2H, J1 = 8.0 Hz and J2 = 1.2 Hz), 7.87 (s, 1H). 13C NMR
(100 MHz, CDCl3) δ: 25.1, 26.6, 52.2, 66.3, 74.0, 110.2,
120.9, 125.6, 128.0, 128.8, 130.5, 147.7. MS (m/z, %):
259 ([M]+, 19), 244 ([M-15]+, 16), 144 (18), 127 (18),
116 (25), 99 (33), 85 (56), 71 (70), 57 (100), 43 (79),
41 (29), 32 (11).
Synthesis of 1-((2,2-dimethyl-1,3-dioxolan-4-
yl)methyl)-4-(3-fluorophenyl)-1H-1,2,3-triazole
(4b)
White solid, prepared in 70% yield, from the
reaction between 1-ethynyl-3-fluorobenzene
(1.70 g, 14.2 mmol) and azide 3 (1.50 g, 9.60
mmol), m.p. 88-91 °C. TLC: Rf = 0.60 (ether-
dichloromethane, 10:1 v v-1); IR (ATR) /cm-1:
3099, 2992, 1620, 1590, 1484, 1465, 1444, 1372, 1293,
1225, 1202, 1149, 1115, 1055, 1026, 969, 865, 835, 755,
687. 1H NMR (400 MHz, CDCl3) δ: 1.33 (s, 3H), 1.38
(s, 3H), 3.75 (dd, 1H, J1 = 8.8 Hz and J2 = 6.0 Hz), 4.12
(dd, 1H, J1 = 8.8 Hz and J2 = 6.4 Hz), 4.42-4.51 (m,

FERNANDO F. BARCELOS et al. SYNTHESIS AND BIOLOGICAL EFFECT OF NEW TRIAZOLES
An Acad Bras Cienc (2023) 95(1) e20211102 4 | 15
2H), 4.58 (dd, 1H, J1 = 12.6 Hz and J2 = 2.6), 6.99 (tdd,
1H, J1 = 8.5 Hz, J2 = 2.5 Hz and J3 = 0.8 Hz), 7.33-7.38
(m, 1H), 7.51-7.59 (m, 2H), 7.90 (s, 1H). 13C NMR (100
MHz, CDCl3) δ: 25.1, 26.6, 52.3, 66.3, 74.0, 110.2, 112.6
(d, JC-F = 22.0 Hz), 114.9 (d, JC-F = 21.0 Hz), 121.2 (d,
JC-F = 3.0 Hz), 121.3, 130.3 (d, JC-F = 8.0 Hz), 132.6 (d,
JC-F = 9.0 Hz), 146.6 (d, JC-F = 3.0 Hz), 163.1 (d, JC-F =
253.0 Hz). MS (m/z, %): 277 ([M]+, 34), 262 ([M-15]+,
32), 248 (10), 219 (21), 206 (11), 190 (10), 177 (9), 162
(37), 148 (28), 134 (40), 120 (24), 101 (33), 83 (10), 73
(20), 57 (44), 43 (100), 41 (48), 31 (10).
Synthesis of 1-((2,2-dimethyl-1,3-dioxolan-4-
yl)methyl)-4-(4-fluorophenyl)-1H-1,2,3-triazole
(4c)
White solid, prepared in 81% yield from the
reaction between 1-ethynyl-4-fluorobenzene
(2.00 g, 16.7 mmol) and azide 3 (1.75 g, 11.1
mmol), m.p. 100-103 °C. TLC: Rf = 0.57 (ether-
dichloromethane, 10:1 v v-1); IR (ATR) /cm-1: 3295,
2986, 2886, 1706, 1590, 1568, 1470, 1431, 1372, 1256,
1226, 1147, 1051, 1034, 971, 879, 831, 755, 676. 1H
NMR (400 MHz, CDCl3) δ: 1.33 (s, 3H), 1.37 (s, 3H),
3.75 (dd, 1H, J1 = 8.8 Hz and J2 = 6.0 Hz), 4.11 (dd,
1H, J1 = 8.8 Hz and J2 = 6.4 Hz), 4.41-4.50 (m, 2H),
4.57 (dd, 1H, J1 = 13.2 Hz and J2 = 3.2), 7.08 (t, 2H, J1 =
8.6 Hz), 7.76-7.79 (dd, 2H), 7.84 (s, 1H). 13C NMR (100
MHz, CDCl3) δ: 25.0, 26.6, 52.2, 66.2, 73.9, 110.1, 115.7
(d, JC-F = 21.0 Hz), 120.6, 126.7 (d, JC-F = 3.0 Hz), 127.4
(d, JC-F = 9.0 Hz), 146.7, 162.6 (d, JC-F = 253.0 Hz). MS
(m/z, %): 277 ([M]+, 35), 262 ([M-15]+, 35), 248 (16),
206 (12), 190 (7), 176 (9), 162 (25), 148 (29), 134 (47),
120 (29), 101 (29), 83 (9), 73 (21), 68 (32), 59 (33), 57
(46), 43 (100), 41 (44), 31 (10).
Synthesis of 1-((2,2-dimethyl-1,3-dioxolan-4-
yl)methyl)-4-(2-fluorophenyl)-1H-1,2,3-triazole
(4d)
Yellow solid, prepared in 85% yield from the
reaction between 1-ethynyl-2-fluorobenzene
(2.00 g, 16.7 mmol) and azide 3 (1.75 g, 11.1 mmol),
m.p. 69-72 °C. TLC: Rf
= 0.72 (ether-dichloromethane,
10:1 v v-1); IR (ATR) /cm-1: 3172, 2994, 2976, 2958,
2926, 1579, 1553, 1485, 1466, 1437, 1370, 1260, 1233,
1217, 1164, 1142, 1107, 1044, 967, 944, 906, 841, 819,
757, 670. 1H NMR (400 MHz, CDCl3) δ: 1.33 (s, 3H),
1.37 (s, 3H), 3.75 (dd, 1H, J1 = 8.8 Hz and J2 = 5.2 Hz),
4.10 (dd, 1H, J1 = 8.8 Hz and J2 = 6.0 Hz), 4.47-4.52
(m, 2H), 4.58 (dd, 1H, J1 = 15.8 Hz and J2 = 6.2), 7.08-
7.13 (m, 1H), 7.20-7.31 (m, 2H), 8.04 (dap, 1H, J = 3.6
Hz), 8.26 (1H, td, J1 = 7.6 Hz and J2 = 2.0). 13C NMR
(100 MHz, CDCl3) δ: 25.1, 26.7, 51.9, 66.1, 73.9, 110.2,
115.6 (d, JC-F = 21.0 Hz), 118.4 (d, JC-F = 16.0 Hz), 124.0
(d, JC-F = 12.0 Hz), 124.5 (d, JC-F = 3.0 Hz), 127.7 (d, JC-F
= 3.0 Hz), 129.2 (d, JC-F = 9.0 Hz), 141.1 (d, JC-F = 3.0
Hz), 159.1 (d, JC-F = 242.0 Hz). MS (m/z, %): 277 ([M]+,
52), 262 ([M-15]+, 52), 248 (7), 219 (21), 206 (14), 190
(12), 177 (14), 162 (50), 148 (36), 134 (46), 120 (27),
107 (24), 101 (36), 83 (9), 68 (20), 59 (35), 57 (48), 43
(100), 41 (47), 31 (12).
Synthesis of 4-(3,4-difluorophenyl)-1-((2,2-
dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-
triazole (4e)
Brown solid, prepared in 78% yield from the
reaction between 3,4-difluorophenylacetylene
(2.00 g, 14.5 mmol) and azide 3 (1.50 g, 9.60
mmol), m.p. 73-75 °C. TLC: Rf = 0.53 (ether-
dichloromethane 10:1 v v-1); IR (ATR) /cm-1: 3138,
3114, 2990, 2927, 1608, 1566, 1509, 1462, 1440, 1370,
1366, 1273, 1239, 1186, 1151, 1117, 1072, 1052, 1005,
968, 882, 822, 773, 718, 628, 603. 1H NMR (400 MHz,
CDCl3) δ: 1.33 (s, 3H), 1.37 (s, 3H), 3.75 (dd, 1H, J1 =
8.8 Hz and J2 = 5.6 Hz), 4.12 (dd, 1H, J1 = 8.8 Hz and
J2 = 6.4 Hz), 4.41-4.50 (m, 2H), 4.58 (dd, 1H, J1 = 13.4
Hz and J2 = 3.0), 7.17 (1H, td, J1 = 10.0 Hz, J2 = 7.8 Hz
and J3 = 1.6), 7.49-7.53 (m, 1H), 7.61-7.66 (m, 1H),
7.86 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 25.0, 26.3,
52.3, 66.1, 74.0, 110.1, 114.7 (d, JC-F = 19.0 Hz), 117.6
(dap, JC-F = 17.0 Hz), 121.0, 121.7 (dd, JC-F = 6.0 Hz and
JC-F = 4.0 Hz), 127.7 (dd, JC-F = 6.5 Hz and JC-F = 3.5
Hz), 145.9, 150.1 (dd, JC-F = 247.5 Hz and JC-F = 12.5
Hz), 150.6 (dd, JC-F = 247.5 Hz and JC-F = 11.5 Hz). MS

FERNANDO F. BARCELOS et al. SYNTHESIS AND BIOLOGICAL EFFECT OF NEW TRIAZOLES
An Acad Bras Cienc (2023) 95(1) e20211102 5 | 15
(m/z, %): 295 ([M]+, 35), 280 ([M-15]+, 37), 266 (12),
237 (17), 224 (12), 208 (9), 180 (28), 166 (22), 152
(36), 138 (23), 125 (18), 119 (10), 101 (21), 83 (7), 73
(20), 68 (19), 57 (32), 43 (100), 41 (47), 31 (10).
Synthesis of 4-(2,4-difluorophenyl)-1-((2,2-
dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-
triazole (4f)
White solid, prepared in 68% yield from the
reaction between 1-ethynyl-2,4-difluorobenzene
(2.00 g, 14.5 mmol) and azide 3 (1.50 g, 9.60
mmol), m.p. 95-97 °C. TLC: Rf = 0.68 (ether-
dichloromethane 10:1 v v-1); IR (ATR) /cm-1: 3178,
3072, 2998, 2960, 1628, 1602, 1559, 1493, 1462, 1416,
1382, 1358, 1266, 1244, 1211, 1165, 1142, 1117, 1068,
1045, 980, 905, 869, 841, 804, 732, 662, 611. 1H NMR
(400 MHz, CDCl3) δ: 1.32 (s, 3H), 1.36 (s, 3H), 3.74
(dd, 1H, J1 = 8.8 Hz and J2 = 5.6 Hz), 4.10 (dd, 1H,
J1 = 8.8 Hz and J2 = 6.0 Hz), 4.45-4.51 (m, 2H), 4.57
(dd, 1H, J1 = 15.8 Hz and J2 = 6.2), 6.83-6.89 (m, 1H),
6.93-6.98 (m, 1H), 7.99 (dap, 1H, J = 3.6 Hz), 8.20-
8.26 (1H, m). 13C NMR (100 MHz, CDCl3) δ: 25.1, 26.3,
51.9, 66.1, 73.9, 104.0 (t, JC-F = 25.5 Hz), 110.1, 111.9
(dd, JC-F = 21.0 Hz and JC-F = 3.0 Hz), 114.9 (dd, JC-F =
13.0 Hz and JC-F = 4.0 Hz), 123.5 (dap, JC-F = 12.0 Hz),
128.7 (dd, JC-F = 9.5 Hz and JC-F = 6.5 Hz), 140.4 (dap,
JC-F = 3.0 Hz), 159.1 (dd, JC-F = 249.0 Hz and JC-F = 12.0
Hz), 162.4 (dd, JC-F = 249.0 Hz and JC-F = 12.0 Hz). MS
(m/z, %): 295 ([M]+, 30), 280 ([M-15]+, 37), 237 (15),
220 (11), 208 (8), 195 (8), 180 (29), 166 (21), 152 (36),
138 (24), 125 (19), 119 (11), 101 (18), 83 (7), 73 (19), 68
(21), 57 (33), 43 (100), 41 (44), 31 (9).
Synthesis of 4-(3,5-difluorophenyl)-1-((2,2-
dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-
triazole (4g)
White solid, prepared in 65% yield from the
reaction between 1-ethynyl-3,5-difluorobenzene
(2.00 g, 14.5 mmol) and azide 3 (1.50 g, 9.6
mmol), m.p. 100-102 °C. TLC: Rf = 0.60 (ether-
dichloromethane 10:1 v v-1); IR (ATR) /cm-1: 3081,
2992, 1626, 1594, 1470, 1434, 1373, 1265, 1227, 1203,
1150, 1117, 1056, 1027, 984, 923, 881, 858, 834, 749,
680, 664. 1H NMR (400 MHz, CDCl3) δ: 1.33 (s, 3H),
1.38 (s, 3H), 3.75 (dd, 1H, J1 = 8.8 Hz and J2 = 5.8 Hz),
4.13 (dd, 1H, J1 = 8.8 Hz and J2 = 6.2 Hz), 4.41-4.50
(m, 2H), 4.59 (dd, 1H, J1 = 13.0 Hz and J2 = 2.6), 6.74
(tt, 1H, J1 = 9.0 Hz and J2 = 2.3 Hz), 7.32-7.35 (m, 2H),
7.91 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 25.0, 26.7,
52.3, 66.4, 74.0, 103.2 (t, JC-F = 25.5 Hz), 108.4 (dd,
JC-F = 19.0 Hz and JC-F = 8.0 Hz), 110.2, 121.5, 133.6 (t,
JC-F = 10.5 Hz), 145.8 (t, JC-F = 3.0 Hz), 163.3 (dd, JC-F =
247.0 Hz and JC-F = 13.0 Hz). MS (m/z, %): 295 ([M]+,
18), 280 ([M-15]+, 31), 237 (8), 220 (11), 208 (8), 180
(24), 166 (16), 152 (28), 138 (16), 125 (16), 119 (9), 101
(23), 83 (7), 73 (18), 57 (28), 43 (100), 41 (50), 31 (9).
Synthesis of 1-((2,2-dimethyl-1,3-dioxolan-4-
yl)methyl)-4-(4-(trifluoromethyl)phenyl)-1H-
1,2,3-triazole (4h)
White solid, prepared in 73% yield from the
reaction between 1-ethynyl-4-(trifluorometyl)
benzene (2.50 g, 14.7 mmol) and azide 3 (1.50 g,
9.60 mmol), m.p. 125-127 °C. TLC: Rf = 0.80 (ether-
dichloromethane 10:1 v v-1); IR (ATR) /cm-1: 3096,
2990, 1621, 1457, 1414, 1384, 1325, 1261, 1230, 1203,
1161, 1115, 1063, 1041, 1015, 970, 913, 881, 833, 782,
687, 658. 1H NMR (400 MHz, CDCl3) δ: 1.33 (s, 3H),
1.38 (s, 3H), 3.76 (dd, 1H, J1 = 8.8 Hz and J2 = 5.6 Hz),
4.13 (dd, 1H, J1 = 8.8 Hz and J2 = 6.4 Hz), 4.43-4.52
(m, 2H), 4.60 (dd, 1H, J1 = 12.6 Hz and J2 = 2.6), 7.65
(d, 2H, J = 8.6 Hz), 7.92 (d, 2H, J = 8.6 Hz), 7.97 (s,
1H). 13C NMR (100 MHz, CDCl3) δ: 25.0, 26.7, 52.3,
66.4, 73.9, 110.1, 121.8, 124.0 (q, JC-F = 270.3), 125.8
(q, JC-F = 3.6), 129.97 (q, JC-F = 32.6), 134.0, 146.3. MS
(m/z, %): 327 ([M]+, 21), 312 ([M-15]+, 37), 298 (7),
269 (34), 256 (13), 240 (12), 227 (7), 212 (33), 198 (17),
185 (24), 170 (7), 151 (11), 134 (11), 116 (7), 101 (25),
83 (7), 73 (20), 68 (13), 59 (29), 57 (36), 43 (100), 41
(52), 31 (10).

FERNANDO F. BARCELOS et al. SYNTHESIS AND BIOLOGICAL EFFECT OF NEW TRIAZOLES
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Synthesis of 1-((2,2-dimethyl-1,3-dioxolan-4-
yl)methyl)-4-(3-(trifluoromethyl)phenyl)-1H-
1,2,3-triazole (4i)
White solid, prepared in 61% yield from the
reaction between 1-ethynyl-3-(trifluorometyl)
benzene (2.50 g, 14.7 mmol) and azide 3 (1.50 g,
9.6 mmol), m.p. 63-65 °C. TLC: Rf = 0.51 (ether-
dichloromethane 10:1 v v-1); IR (ATR) /cm-1: 3155,
2991, 2945, 1621, 1459, 1419, 1382, 1346, 1309, 1263,
1228, 1206, 1164, 1124, 1096, 1067, 1040, 1000, 985,
892, 831, 800, 717, 693, 649. 1H NMR (400 MHz,
CDCl3) δ: 1.34 (s, 3H), 1.39 (s, 3H), 3.77 (dd, 1H, J1 =
8.7 Hz and J2 = 5.8 Hz), 4.12 (dd, 1H, J1 = 8.7 Hz and
J2 = 6.0 Hz), 4.43-4.52 (m, 2H), 4.61 (dd, 1H, J1 = 12.8
Hz and J2 = 2.8), 7.52 (t, 1H, J = 7.6 Hz), 7.56 (d, 1H,
J = 8.0 Hz), 7.96 (s, 1H), 8.01 (d, 1H, J = 7.2 Hz), 8.06
(s, 1H). 13C NMR (100 MHz, CDCl3) δ: 25.0, 26.6, 52.3,
66.3, 74.0, 110.3, 121.2, 122.4 (q, JC-F = 4.0), 123.9 (q,
JC-F = 269.6), 124.6 (q, JC-F = 3.6), 128.8, 129.4, 131.2 (q,
JC-F = 32.0), 131.3, 146.2. MS (m/z, %): 327 ([M]+, 17),
312 ([M-15]+, 31), 298 (6), 269 (29), 256 (11), 240 (10),
227 (7), 212 (30), 198 (15), 184 (24), 170 (7), 151 (10),
134 (8), 116 (5), 101 (22), 83 (7), 73 (19), 68 (13), 59
(23), 57 (33), 43 (100), 41 (51), 31 (8).
Synthesis of 1-((2,2-dimethyl-1,3-dioxolan-4-
yl)methyl)-4-(2-(trifluoromethyl)phenyl)-1H-
1,2,3-triazole (4j)
Red solid, prepared in 58% yield from the
reaction between 1-ethynyl-2-(trifluorometyl)
benzene (2.50 g, 14.7 mmol) and azide 3 (1.50 g,
9.60 mmol), m.p. 51-53 °C. TLC: Rf = 0.73 (ether-
dichloromethane 10:1 v v-1); IR (ATR) /cm-1: 2999,
2933, 1609, 1579, 1441, 1383, 1374, 1315, 1254, 1214,
1167, 1127, 1110, 1085, 1067, 1056, 1035, 995, 966,
879, 822, 773, 713, 683, 665, 645. 1H NMR (400 MHz,
CDCl3) δ: 1.33 (s, 3H), 1.36 (s, 3H), 3.76 (dd, 1H, J1 =
8.9 Hz and J2 = 5.4 Hz), 4.12 (dd, 1H, J1 = 8.9 Hz and
J2 = 5.8 Hz), 4.46-4.52 (m, 2H), 4.60 (dd, 1H, J1 = 16.0
Hz and J2 = 6.4), 7.46 (t, 1H, J = 7.0 Hz), 7.61 (t, 1H, J
= 7.6 Hz), 7.73 (d, 1H, J = 8.0 Hz), 7.89 (s, 1H), 7.96
(d, 1H, J = 8.4 Hz). 13C NMR (100 MHz, CDCl3) δ: 25.0,
26.3, 51.9, 66.1, 73.9, 110.2, 124.1 (q, JC-F = 256.0), 124.2
(q, JC-F = 5.6), 126.0 (q, JC-F = 5.6), 127.2 (q, JC-F = 28.0),
128.1, 129.4 (q, JC-F = 2.0), 131.6, 131.9, 144.0. MS (m/z,
%): 327 ([M]+, 11), 312 ([M-15]+, 42), 269 (38), 256
(20), 240 (13), 212 (29), 198 (16), 184 (20), 165 (19),
151 (17), 134 (11), 115 (7), 101 (26), 83 (8), 73 (21), 59
(32), 57 (41), 43 (100), 41 (50), 31 (10).
Synthesis of 4-(3,5-bis(trifluoromethyl)
phenyl)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)
methyl)-1H-1,2,3-triazole (4k)
White solid, prepared in 74% yield from
the reaction between 1-ethynyl-3,5-
bis(trifluoromethyl)benzene (3.50 g, 14.7 mmol)
and azide 3 (1.50 g, 9.60 mmol), m.p. 60-63 °C.
TLC: Rf = 0.17 (hexane-dichloromethane 1:1 v v-1);
IR (ATR) /cm-1 : 2933, 1465, 1383, 1321, 1276, 1234,
1210, 1173, 1130, 1107, 1079, 1045, 997, 966, 894, 828,
810, 749, 699, 680. 1H NMR (400 MHz, CDCl3) δ: 1.34
(s, 3H), 1.40 (s, 3H), 3.78 (dd, 1H, J1 = 8.8 Hz and J2
= 6.0 Hz), 4.16 (dd, 1H, J1 = 8.8 Hz and J2 = 6.4 Hz),
4.44-4.53 (m, 2H), 4.64 (dd, 1H, J1 = 13.0 Hz and J2 =
2.6), 7.80 (s, 1H), 8.05 (s, 1H), 8.26 (s, 2H). 13C NMR
(100 MHz, CDCl3) δ: 25.1, 26.6, 52.7, 66.2, 73.8, 110.2,
121.5 (dqap, JC-F = 3.7), 121.9, 123.1 (q, JC-F = 271.3),
125.5 (q, JC-F = 2.6), 132.2 (q, JC-F = 33.3), 132.7, 144.9.
MS (m/z, %): 395 ([M]+, 11), 380 ([M-15]+, 65), 376
(19), 337 (89), 320 (17), 308 (11), 280 (28), 266 (16),
252 (25), 240 (12), 219 (7), 169 (8), 101 (41), 83 (7), 73
(19), 57 (27), 43 (100), 41 (52), 31 (8).
Biological Assays
Plant Material
The evaluation of phytotoxicity and cytogenoxicity
of compounds 4a-4k were performed using
commercial seeds of the plant model Lactuca
sativa L. “Crespa Grand Rapids - TBR” (ISLA).
Phytotoxicity evaluation
The phytotoxicity evaluation of the compounds
4a-4k were conducted using five different

FERNANDO F. BARCELOS et al. SYNTHESIS AND BIOLOGICAL EFFECT OF NEW TRIAZOLES
An Acad Bras Cienc (2023) 95(1) e20211102 7 | 15
concentrations (1000, 500, 250, 100, 50 g mL-1) of
each compound. Twenty-five lettuce seeds were
placed in each Petri dishes (9 cm in diameter)
containing filter paper moistened with solution
(2.5 mL) from each treatment. The experiments
followed a completely randomized design
(CRD), with four repetitions per treatment. The
dishes were sealed with transparent plastic
film to prevent evaporation and kept moist
BOD (Biochemical Oxygen Demand) at 25 °C ±
2 ºC without light throughout the experiment
period. As a negative control, distilled water and
dichloromethane (99.5% v v-1) were used. The
commercial herbicide picloram 0.1% was utilized
as a positive control. The germination process
was evaluated from 8 to 48 h, at 8 h intervals.
The macroscopic parameters evaluated were the
germination speed index (GSI), the percentage
of germinated seeds (GR), root length after 48
h (RL) and aerial growth (AG) after 120 h, as
previously described (Pinheiro et al. 2015).
Cytogenotoxic evaluation
After 48 hours of exposure to treatments, the
roots of L. sativa were collected and fixed in
ethanol-acetic acid (3:1 v v-1). Fixer changes
were made within 10 min and 24 h after the
first fixation, being stored at -20 °C during the
entire process. After 24 h, slides from the root
meristems were prepared using the crushing
technique and stained with 2% acetic orcein
(Andrade-Vieira et al. 2012). Approximately 4.000
meristematic cells were evaluated per treatment,
observing, and quantifying the different phases
of mitotic division, possible chromosomal,
and nuclear changes. The mitotic index (MI)
was obtained by dividing the number of cells
in division (prophase, metaphase, anaphase,
and telophase) by the total number of cells
evaluated in each treatment. The frequencies
of chromosomal and nuclear changes were
obtained by dividing the number of changes,
chromosomal, and nuclear, respectively, by
the total number of cells evaluated (Andrade-
Vieira et al. 2012). The frequency of changes,
which represents the occurrence of each change
individually, was assessed based on the ratio
between the number of changes individually
(c-metaphase, bridge, sticky, delay, brake and
lost) and the number of cells per division
(Andrade-Vieira et al. 2012). The analysis of the
slides was performed using a Nikon eclipse 80i
microscope. The interest images were captured
on a Nikon Plan Fluor 100x/1.30 oil OFN25 DIC
H/N2 objective, with a Nikon DS camera – Fi1c
attached to the microscope.
Statistics Analysis
For phytotoxicity and cytogenotoxicity analyzes,
the data obtained were subjected to analysis of
variance and the means compared by Dunnett’s
test (p<0.05), as it is the most suitable for
experiments that seek to compare treatments
with controls (McHugh 2011). All analyses were
performed using the statistical analysis program
GENES VS 2015.5.0 (Cruz 2013).
RESULTS AND DISCUSSION
Preparation of compounds 4a-4k
The synthetic steps involved in the preparation
of the compounds 4a-4k, herein investigated,
are outlined in Figure 1. Glycerol was converted
to acetonide 1 in 63% yield by treatment of
the triol with acetone in the presence of TsOH
and CuSO4. Then, the reaction of acetonide 1
with p-toluene sulphonyl chloride gave the
corresponding ester sulfonate 2 in 75% yield.
The reaction between 2 and sodium azide
resulted in the formation of 3 in 93%. Finally,
the Cu(I)-catalyzed alkyne-azide cycloaddition
reaction (CuAAC reaction, also known as the click
reaction) (Costa et al. 2017, 2020, Aher et al. 2009,
Agalave et al. 2011, Borgati et al. 2013) between

FERNANDO F. BARCELOS et al. SYNTHESIS AND BIOLOGICAL EFFECT OF NEW TRIAZOLES
An Acad Bras Cienc (2023) 95(1) e20211102 8 | 15
azide 3 and different commercially available
aromatic terminal alkynes afforded the glycerol
1,2,3-triazoles derivatives 4a-4k in 58-85%
yields. The structures of 4a-4k were confirmed
by IR and 1H and 13C NMR spectroscopy as well
as mass spectrometric analyses. In IR spectra,
the band corresponding to the =C-H stretching
was observed within the 3081-3178 cm-1 range,
while the N=N stretching of the triazole ring
was noted within the interval 1626-1579 cm-1. In
the 1H NMR spectra, signals corresponding to
the hydrogens of the triazole ring and methyl
groups of acetonide were observed within 7.80-
7.97 and 1.32-1.40 ppm, respectively. In 13C NMR
spectra, signals for methyl acetonide group
were observed within 25.0-26.7 ppm range, while
carbons from the triazole portion appeared
at 120.6-147.7 ppm. Molecular formulas of the
glycerol 1,2,3-triazole derivatives were confirmed
based on mass spectrometry analyses.
Once synthesized, the compounds 4a-
4k were submitted to the evaluation of their
phytotoxic and cytotoxic activities.
Phytotoxicity Evaluation
The analysis of the phytotoxicity evaluation data
(Figure 2) revealed that compounds 4a, 4b, 4d,
and 4i were the ones that presented effects on
seed germination. The derivative 4a at 1000 g
mL-1 inhibited approximately 25% of L. sativa
seed germination, an effect that was similar
to the positive control picloram. Compounds
4b and 4d (at 500 g mL-1 ) and 4i (at 1000 and
500 g mL-1 ) also inhibited germination when
compared to the negative controls (Figure 2).
Compound 4a, at the highest concentration,
presented an effect on GSI similar to picloram,
inhibiting GSI by 65% as compared to negative
controls. The derivatives 4a (at 500 g mL-1), 4b (at
1000, 500, and 250 g mL-1 ), 4d and 4e (at 1000, 500
g mL-1), 4i and 4j (at 1000, 500 g mL-1 ) promoted
inhibition on the GSI when compared to the
negative controls (Figure 2). Some compounds,
4b, 4d, 4e, 4i, and 4j, showed inhibitory effects
only on this germination parameter, presenting
no difference when compared to the percentage
of final germination. This is a characteristic
Figure 1. Synthetic
route for the
preparation of
glycerol derivatives
4a-4k.

FERNANDO F. BARCELOS et al. SYNTHESIS AND BIOLOGICAL EFFECT OF NEW TRIAZOLES
An Acad Bras Cienc (2023) 95(1) e20211102 9 | 15
found in compounds classified as biocides
(Iganci et al. 2006).
Regarding root growth, the triazole 4i (at 1000
and 500 g mL-1 ) was equipotent to picloram,
inhibiting approximately 80% of root lettuce
development as compared to the negative
controls (Figure 2). The compounds 4b and 4j
(at 1000, 500, and 250 g mL-1), 4d and 4e (at
1000 and 500 g mL-1 ), 4a (at 1000 g mL-1), and
4i (at 250 and 100 g mL-1) inhibited root growth
as compared to the negative controls (Figure
2). On the contrary, compound 4c (at 250, 100,
and 50 g mL-1) stimulated growth. Root growth
a parameter is considered the most sensitive
among those analyzed in the phytotoxicity
evaluation assays, being responsive even
for compounds displaying mild/moderate
toxicity (Aragão et al. 2017). Besides, when the
germination process of the plant begins, there
is the imbibition of liquid before germination
and the greatest absorption of the compound
occurs. For this reason, RG is one of the most
affected parameters, since the roots are the first
to have direct contact with the compound, being
the largest consumers of nutrients and liquid
retained in the seed (Aragão et al. 2017).
Figure 2. Phytotoxicity evaluation of triazoles 4a-4k. The effects of the compounds were assessed on the plant
model Lactuca sativa at five concentrations. Positive control was picloram and negative controls corresponded to
dichloromethane and water. The G% = germination percentage; GSI = Germination Speed Index; RG = Root Growth;
AG = Aerial Growth. The means followed by the letter a were equal to the negative control water, those followed by
the letter b were equal to the negative control dichloromethane and those followed by the letter c were equal to
the positive control picloram (0.1%) according to the Dunnett test (p <0.05).

FERNANDO F. BARCELOS et al. SYNTHESIS AND BIOLOGICAL EFFECT OF NEW TRIAZOLES
An Acad Bras Cienc (2023) 95(1) e20211102 10 | 15
In terms of the aerial growth (AG)
analyses, the compounds 4a, 4b, 4d, 4e, 4f,
4g, and 4h showed statistical difference at all
concentrations when compared to the negative
control, and the non-statistical difference was
noticed regarding the positive control. The AG
inhibition was higher than 80% when compared
to the negative control (Figure 2). The triazole 4i
(at 1000, 500, 250, and 100 g mL-1) and 4c and 4j
(at 1000 and 500 g mL-1 ) also showed AG equal
to the positive control (Figure 2). The based-
triazole commercial herbicide Front® has a pre-
emergent character, and it acts by inhibiting
photosynthesis through photosystem II. These
three new synthetic 1,2,3-triazoles (4c, 4i, and 4j)
may be acting on the same metabolic pathway as
the commercial herbicide. With the consumption
of the energy retained in the seed by the root
growth, the seed loses vigor to aerial growth,
which in turn is prevented from performing
photosynthesis to recover the plant, leading to
a slower growth rate and subsequently causing
the death of it (Toledo et al. 2010).
Although less effective than the commercial
herbicide used as a positive control, the
compound 4k at all tested concentrations, 4j
(at 250 and 100 g mL-1), and 4i (at 50 g mL-
1) inhibited the AG when compared to negative
controls (Figure 2).
Still considering AG, it was possible to
observe that the compound 4c (at 250, 100, and 50
g mL-1) induced growth, differing from controls
(Figure 2). Some molecules have an inducer
potential when used at low concentrations,
behaving as a synthetic auxin. This increase may
be related to the elongation of cells that occurs
during the process of cell growth and derivation
(Aragão et al. 2017).
The analysis of phytotoxic parameters,
such as the percentage of germination and
the germination speed index can indicate if a
compound presents pre-emergent inhibition
behavior, while the investigation of root and
aerial growth can provide information regarding
the post-emergent inhibition effect (Vargas &
Roman 2006). Thus, the compounds 4a, 4b, 4d, 4e,
4i, and 4j have pre-emergent inhibition behavior,
while all the investigated compounds showed
post emergent effect (Figure 2). The knowledge
of the action of compounds concerning the
emergence of a plant is an important feature to
be considered. A pre-emergent compound does
not allow seed germination; directly related
to plantations to be implanted, it can act on
invasive plants before they start to compete
with the culture of interest. On the other hand,
a compound with post-emergent behavior can
be used for cultures already installed (Vargas &
Roman 2006).
Cytogenotoxic Evaluation
In the cytogenotoxic assessment, the compounds
promoted both increase and decrease in the
mitotic index. The increase was caused by 4k (at
500, 250, 100, and 50 g mL-1), 4a, 4b, 4g, 4h (at
250, 100, and 50 g mL-1), 4d, 4f (at 100 and 50
g mL-1), and 4c, 4e, and 4j (at 50 g mL-1). The
decrease was observed in meristematic cells
treated with 4i (1000, 500, and 250 g mL-1 ), and
4a, 4c, 4d, 4e, 4f, 4g, 4h, and 4i (1000 g mL-1)
(Figure 3). The increase in MI can occur when a
plant tries to develop to leave a stressed place,
while the decrease can occur due to cell death
(Iganci et al. 2006).
All the studied compounds caused an
increase in nuclear alterations at certain
concentrations. Changes such as micronuclei or
condensed nuclei were observed for 4a, 4b, and
4d (Figure 3). For the other derivatives, only a
condensed nucleus was observed, which is the
cytological evidence of the occurrence of cell
death (Andrade-Vieira et al. 2012).
An increase in CA was observed for
compounds 4d, 4e, 4f, 4g, 4h, 4j, and 4k, at

FERNANDO F. BARCELOS et al. SYNTHESIS AND BIOLOGICAL EFFECT OF NEW TRIAZOLES
An Acad Bras Cienc (2023) 95(1) e20211102 11 | 15
all concentrations. In the case of 4a (at 250,
100, and 50 g mL-1 ), 4c (at 500, 250, 100, and
50 g mL-1 ), and 4i, (at 1000, 500, 100, and 50),
an increase in CA was also noticed (Figure 3).
Chromosomal alterations are determined by
the number of chromosomes in abnormalities,
whether structural or numerical. These changes
can be classified according to the mechanism of
action as clastogenic, aneugenic, and epigenetic
(Bernardes et al. 2015, Freitas et al. 2016). One
of the alterations found was Stick, which was
observed for all compounds, except in the case
of 4a and 4b (Figure 4). This alteration is classified
as clastogenic, aneugenic, and epigenetic
(Freitas et al. 2016, Silveira et al. 2017, Dos Santos
et al. 2019). Another alteration observed for 4e,
4f, 4i, and 4k derivatives was Bridge (Figure 4),
which is classified as clastogenic according to
its mechanism of action (Dos Santos et al. 2019).
The aneugenic observed changes corresponded
to delay, c-metaphase, and loss (Figure 4).
The delay was observed for most compounds,
not being found only for 4a-4c (Figure 4).
C-metaphase was observed for 4g, 4i, 4j, and
4k (Figure 4), resulting from the inactivation of
the spindle (Fernandes et al. 2009). Another
Figure 3. Cytogenotoxic variables evaluated in Lactuca sativa meristematic cells treated with five concentrations
of triazoles 4a to 4k and positive control (picloram) and negative controls (water and dichloromethane) (l). Where:
MI = Mitotic index; CA = Chromosome alterations; NA = Nuclear alterations; MNC = Micronucleus; CN = Condensed
nucleus. The means followed by the letter a were equal to the negative control water, those followed by the
letter b were equal to the negative control dichloromethane and those followed by the letter c were equal to the
positive control picloram (0.1%) according to the Dunnett test (p <0.05).

FERNANDO F. BARCELOS et al. SYNTHESIS AND BIOLOGICAL EFFECT OF NEW TRIAZOLES
An Acad Bras Cienc (2023) 95(1) e20211102 12 | 15
alteration observed only for 4k was lost (Figure
4), which occurs due to abnormal functioning of
the microtubules, leading to the non-alignment
of chromosomes during mitotic division (Dos
Santos et al. 2019). Examples of the cell cycle
alterations in meristematic cells of L. sativa can
be seen in Figure 5.
In summary, using as starting material the
readily available glycerol, a series of eleven
1,2,3-triazole derivatives were synthesized
in four steps. Ten of these compounds were
novel fluorinated derivatives. The evaluation
of the compounds on Lactuca sativa revealed
that they presented effects on phytotoxic and
cytogenotoxic parameters with different degrees
of efficiency. The compounds 4a, 4b, 4d, 4e, 4i,
and 4j have pre-emergent inhibition behavior,
while the compounds 4a, 4b, 4d, 4e, 4f, 4g, 4h,
and 4i showed post emergent effect at all tested
concentrations, evidencing the efficiency of low
concentrations in inhibiting plant shoot growth.
The cytogenotoxic parameters corroborate the
phytotoxic data, with clastogenic, aneugenic
and epigenetic action of the compounds in
roots meristematic cells. It is believed that the
glycerol-fluorinated triazole the scaffold can be
Figure 4. Frequency of chromosomal alterations (Lost, sticky, c-metaphase, bridge, delay and break) observed
in Lactuca sativa meristematic cells treated with five concentrations of triazoles 4a to 4k and positive control
(picloram) and negative (water and dichloromethane) (l). The means followed by the letter a were equal to the
negative control water, those followed by the letter b were equal to the negative control dichloromethane and
those followed by the letter c were equal to the positive control picloram (0.1%) according to the Dunnett test (p
<0.05).

FERNANDO F. BARCELOS et al. SYNTHESIS AND BIOLOGICAL EFFECT OF NEW TRIAZOLES
An Acad Bras Cienc (2023) 95(1) e20211102 13 | 15
explored toward the development of new active
ingredients to control weeds.
Acknowledgments
The authors thank the Fundação de Amparo à Pesquisa
do Estado do Espírito Santo (Fapes), the Conselho
Nacional de Desenvolvimento Científico e Tecnológico
(CNPq). This study was funded in part by the Coordenação
de Aperfeiçoamento de Pessoal de Nível Superior- Brasil
(CAPES) - Finance Code 001.
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How to cite
BARCELOS FF ET AL. 2023. Synthesis of novel glycerol-fluorinated triazole
derivatives and evaluation of their phytotoxic and cytogenotoxic
activities. An Acad Bras Cienc 95: e20211102. DOI 10.1590/0001-
3765202320211102.
Manuscript received on August 5, 2021;
accepted for publication on April 17, 2022
FERNANDO F. BARCELOS1
https://orcid.org/0000-0001-5914-9924
THAMMYRES A. ALVES2
https://orcid.org/0000-0003-1148-4832
POLIANA A.R. GAZOLLA3
https://orcid.org/0000-0002-0613-9092
RÓBSON RICARDO TEIXEIRA3
https://orcid.org/0000-0003-3181-1108
VAGNER T. DE QUEIROZ4
https://orcid.org/0000-0002-8170-125X
MILENE M. PRAÇA-FONTES2
https://orcid.org/0000-0001-7738-9518
PEDRO A.B. MORAIS4
https://orcid.org/0000-0001-5501-7350
VICTOR R. FONSECA5
https://orcid.org/0000-0002-3592-1972
WANDERSON ROMÃO5
https://orcid.org/0000-0002-2254-6683
VALDEMAR LACERDA JÚNIOR5
https://orcid.org/0000-0002-8257-5443
RODRIGO SCHERER6
https://orcid.org/0000-0001-7656-0248
ADILSON V. COSTA4
https://orcid.org/0000-0002-7968-8586
1Universidade Vila Velha, Programa de Pós-graduação
em Biotecnologia Vegetal, Rua José Dantas de Melo,
21, Boa Vista, 29102-770 Vila Velha, ES, Brazil
2Universidade Federal do Espírito Santo,
Departamento de Biologia, Alto Universitário, s/n,
Guararema, 29500-000 Alegre, ES, Brazil

FERNANDO F. BARCELOS et al. SYNTHESIS AND BIOLOGICAL EFFECT OF NEW TRIAZOLES
An Acad Bras Cienc (2023) 95(1) e20211102 15 | 15
3Universidade Federal de Viçosa, Departamento de
Química, Av. P.H. Rolfs, s/n, 36570-900 Viçosa, MG, Brazil
4Universidade Federal do Espírito Santo, Departamento
de Química e Física, Alto Universitário, s/n,
Guararema, 29500-000 Alegre, ES, Brazil
5Universidade Federal do Espírito Santo, Laboratório de
Petroleômica e Forense, Departamento de Química, Av.
Fernando Ferrari, 514, 29075-910 Vitória, ES, Brazil
6Universidade Vila Velha, Programa de Pós-graduação
em Ciências Farmacêuticas, Rua José Dantas de Melo,
21, Boa Vista, 29102-770 Vila Velha, ES, Brazil
Correspondence to: Adilson Vidal Costa
E-mail: avcosta@hotmail.com
Author contributions
Fernando F. Barcelos: Conceptualization, methodology,
investigation, data curation and writing - original draft.
Thammyres de A. Alves: Conceptualization, visualization,
methodology, formal analysis, writing – review, editing
and supervision. Poliana A. R. Gazolla: Conceptualization,
investigation and data curation. Róbson R. Teixeira:
Conceptualization, methodology, investigation and writing -
original draft. Vagner T. de Queiroz, Milene M. Praça-Fontes,
Pedro A. B. Morais, Victor R. Fonseca, Wanderson Romão,
Valdemar L. Júnior, Rodrigo Scherer: Conceptualization,
formal analysis and writing - original draft & Adilson V. Costa:
Conceptualization, resources, visualization, formal analysis,
writing - review & editing, supervision and financing.