Plant-parasitic nematodes (PPNs) cause approximately $157
billion of annual crop losses globally. Among them, root-knot
group have reported that 1,2,3-benzotriazin-4-one derivatives V2
and V3 exhibited good control efficacy against the cucumber
root-knot nematode disease caused by Meloidogyne incognita at
1
nematodes (RKNs), Meloidogyne spp., are considered as the
most damaging nematode group in the world as they result in
approximately 5% of global crop loss to most cultivated plant
-1
the concentration of 10.0 mg L , which implied that 1,2,3-
benzotriazin-4-one derivatives might be potential for novel
2-4
19,20
species such as tomato, pepper, watermelons and onions.
promising nematicides.
Analyzing the structure characteristic
Traditional nematocides such as fosthiazate, fenamiphos,
oxamyl, dazomet, 1,3-dichloropropene and metham sodium have
been applied for many years. However, some of these chemicals
are gradually being phased out because of their bad
environmental impact. At present, fosthiazate and abamectin are
the most commonly used nematocides in the market. Although
recently some stars of nematocide industry have entered the
pesticide market like fluensulfone and tioxazafen (Figure 1), it
is not enough for the increasingly stringent regulatory
requirements for protecting the environment and ensuring food
safety. Therefore, it is urgent to develop environment-friendly
alternatives for PPNs control.
of these lead compounds, we found that the structure includes
three parts: 1,2,3-benzotriazin-4-one, linker, heterocycle or
aromatic ring. The trial of changing heterocycle and the effect of
substituents on 1,2,3-benzotriazin-4-one ring have been
19,20
investigated before , so we focus our attention on the change
of linker now. In crop protection and bioactive chemicals,
thiourea and acylthiourea have been reported to display a variety
of biological activities, such as insecticidal, fungicidal,
5-7
8
2
1-26
With all this in mind, we
introduced thiourea and acylthiourea into 1,2,3-benzotriazin-4-
one structure as linker to investigate the effect of the linker type
on the nematicidal bioactivity, and designed two series of novel
1,2,3-benzotriazin-4-one derivatives (Fig.2 A and B). Herein, we
described the molecular design, synthesis and preliminarily
discussion about the relationship between structure and
nematicidal activities against Meloidogyne incognita in vivo.
1
,2,3-Benzotriazin-4-one (2) was prepared according to the
27
method in reported literature. As depicted in Scheme 1, the
compound 3 was readily prepared via N-alkylation of 1,2,3-
Benzotriazin-4-one at the
bromopropyl)isoindoline-1,3-dione as an alkylation agent.
Subsequently, the compound was hydrolysis to 3-(3-
3
position, with 2-(3-
3
aminopropyl)benzo[d][1,2,3]triazin-4(3H)-one (4) in the
presence of hydrazine through Gabriel's primary amine synthesis.
2
As shown in Scheme 2, arylamines 5 reacted with CS under
the organic base (triethylene diamine) condition to afford
intermediates 6. Then intermediates 6 reacted with triphosgene in
Figure 1. Some representative nematicides.
3
CHCl to produce aryl isothiocyanates (7). Benzoyl chlorides (9)
1
,2,3-Benzotriazine-4-one is an important class of nitrogen-
were readily prepared via chloroformylation reaction. Then, aroyl
isothiocyanates (10) were synthesized by benzoyl chlorides
reacted with ammonium thiocyanate under the condition of PEG-
containing heterocycle and has attracted much attention in both
the medicinal and agrochemical fields.
pharmacological properties for this class of compounds have
been reported, including drugs with sedative, anesthetic,
antitumor, antiarthritic, diuretic and antitubercular activities.
,2,3-Benzotriazine-4-one structure has also been applied on
organophosphorus insecticide such as azinphos-ethyl and
azinphos-methyl, which can be used for crops pests prevention
and control. As shown in Figure 2, the 1,2,3-benzotriazin-4-one
derivative also exhibited nematicidal activity. Compound V1
9-11
For example, many
400 as phase transfer catalyst. Finally, the title compounds
1
2-17
And,aroyl isothiocyanates (10) reacted with amine (4) to produce
the title compounds B1−B11 (Scheme 1). The structures of the
1
1
13
title compounds were well-characterized by H NMR, C NMR,
IR, and HRMS (ESI).
18
could inhibit Anguillula nematodes. In addition, our research
Figure 2. Design strategy for the synthesis of 1,2,3-benzotriazin-4-one derivatives containing thiourea and acylthiourea.