Synthesis and insecticide evaluation of some new oxopropylthiourea compounds as insect growth regulators against the cotton leafworm, Spodoptera littoralis

In this project we aim to share in increasing the production of the most important non-food agricultural product i.e. cotton via protection of it is plant. The usage of safe alternatives to the pesticides has become crucial due to several serious issues associated with the use of insecticides. Therefore, the families of new eco-friendly organic compounds that contain manly oxopropylthiourea scaffold will synthesis in their pure state by using green procedures. This compounds includes (i) poly functional substituted oxopropylthiourea, (ii) dihydroquinoline carboxylic acid, In second category, the structure of this compounds which may be related to the most famous insect growth regulators insecticides, will confirmed by elemental and modern spectroscopic analyses (such as IR, UV, 1HNMR and 13CNMR). In the final category, the synthesized compounds was checked toward the second & forth instar larvae of cotton leafworm, Spodoptera littoralis. The present data proved that values of LC50 of the most effected synthesized compound 8 was 2.412 ppm in which LC50 for commercial lufenuron was 2.295 ppm. Component 8 may be particularly effective due to the presence of fluorophenyl, cyanoacetamide, and carboxalic acid groups in their chemical makeup. In an additional effort to slightly improve insecticidal compounds, evaluation of the latent effects of the examined components on a number of biological parameters, such as adult longevity, pupal weight, proportion of normal, deformed pupae, & adult emergency, fecundity, & egg hatchability, was carried out.

from the perspective of environmental safety, the combination of such bioactive compounds with insecticides was researched [8][9][10] .In particular, when it comes to pesticides, the majority of urea compounds have a wide range of bioactivities, including insecticidal 11 , antifungal 12 , herbicidal 13 , and antitumor 14 effects.In order to improve the insecticidal profile of triazone insecticides and mimic the molecular mechanism of action of pymetrozine and other TRP antagonists, thiourea bridge groups were added.This led to the synthesis of four different novel triazone analogues, which were then studied.For instance the insect growth regulator lufenuron (match), which has a wide range of bioactivity against lepidopteran and coleopteran pests, suppresses the development of chitin, throws off the hormonal balance during the moulting process, and does both.(Fig. 1) 15 .
In this investigation, we examine how these synthetic IGR-related chemicals affect S. littoralis.This study compares the toxicities of these synthesized compounds and the standard lufenuron against S. littoralis 16,17 .accordingly, this work was aiming to (1) designing & characterizing of different compounds of poly functional substituted oxopropylthiourea.(2) Investigating their insecticidal effectiveness toward S. littoralis.Our data is measured the first phase in insecticide discovery which it might be appreciated for insecticidal activity companies to enhance novel insecticides toward noctuid moths.These new compounds' insecticidal properties were assessed, and structure-activity connections were examined.

Materials and methods
Chemical compounds and reagents.All synthesized compounds were estimate melting point by a Fisher-John mechanical technique.In our search the instrumentations, chemical compounds & solvents have been acquired from Sigma-Aldrich.The infra-red spectra of the designed products were analyzed employed potassium bromide technique, 1 HNMR & 13 CNMR were recorded on spectrometer model Bruker Advance 400 MHz.A reference Lufenuron insecticides were acquired from Sigma-Aldrich.

Laboratory bioassay screening.
9][20][21][22][23] preparation of the compound stocks to create 1000 ppm, 0.1 g of compounds 1-10 were dissolved in 5 mL of Dimethyl formamide & combined with 100 mL of distilled H 2 O. Until usage, the stocks were kept in a refrigerator.The target substances' test results were noted, & the concentrations needed to destroy 50% (LC 50 ) of S. littoralis larvae were calculated.Oxopropylthiourea derivatives were employed in five different concentrations, & 0.1% Tween 80 was employed as a surfactant.Castor bean leaf discs (nine centimeters in diameter) were dipped in the concentration under test for ten seconds, then fed to 2th & 4th larvae, which were roughly the same size and housed in glass jars (five lb).Each action carried out 3 times with ten larvae each.The castor bean leaf has been used in our study, they were collected from the Shandaweel research station geographic area, Sohag governorate, Egypt and we are confirmed that, it is accordance with relevant institutional, national and international guidelines and legislation.

Statistical analysis.
The mortality equalized via Abbott's formula 24 .Calculations of mortality setback line were measurably rummage via probity analysis 25 .Harmfulness index was strongminded via sun equations 26 .The mortality results of larval insect were estimated through employing probit analysis through a statistics (LDPline) equation which estimate the LC 50 values with 95% fiducially limits of lower, upper confidence limit and slope.
A solution of component 1 (4 mol) in dry acetone (20 ml), (4 mol) of amine derivatives, (1 mL) conc.HCl and (0.2 gm) anhydrous ZnCl 2 .The reaction mixture allowed to reflux about 8 h.Cooled and poured to H 2 O.The crystal product was collection via filtration.
Toxicological effectiveness checking for 2nd larvae.The procedure was carried out in accordance with the published method as part of our ongoing research into bioactive thioura derivatives. 30,31According to Table 1 the result of synthesized target compounds 1-10 were tested against 2nd larvae insect of S. littoralis.The bioefficacy results of tested compounds against the 2nd larvae exhibit from high to low toxicological activity this order revealed that the homologous response of the treated strain of S. littoralis which presented variation in response against of target synthesized products.

Biological studies.
According the reported method to determinates the biological characteristics of the thiourea derivatives such larval and pupal duration, pupal weight, the percentage of normal, malformed pupae, and adult emergency, as well as the percentage of fecundity and egg hatchability, were assessed for the latent effects of the investigated component 32 .Activity of the synthetic target components 2, 3, 4, 6 and 8 under test on some biological characteristics of S. littoralis.Recently molted fourth instar larvae of S. littoralis were fed caster bean leaves treated with LC 25 concentrations of the most poisonous Oxopropylthiourea derivatives 2, 3, 4, 6 and 8 for 48 h before being switched to untreated leaves until pupation as part of an investigation into the biological characteristics of the species.Tables 2 and 3 present the findings after recording the key biological characteristics.
Larval and pupal duration.According to the data as shown in

Structure-action relationship (SAR)
Herein, the creation of novel, bioactive, polyfunctional substituted oxopropylthiourea compounds was deemed useful.By using a computerised regression analysis programme and confirming the toxicity value in Table 1 and Fig. 4, the median lethal concentration (LC 50 ) & slope values of the targeted components were determined & expressed as parts per million (ppm).The insecticidal efficiency of the designed components (1-10) were compared with lufenuron teword S. littoralis, in which second instar larvae of S. littarolis are characterized via black lines & forth instar larvae of S. littoralis are signified via red lines after 3 days of treatment (Fig. 5).In this section the structure-action relationship was recognized component 8 is more performance toward 2nd & 4th larvae instar of S. littoralis insect than the other oxopropylthioureas.The high activity of product 8 this is occurrence of fluorophenyl, cyanoacetamide & carboxalic acid group in its structure.Existence of fluorophenyl & carbonitrile groups in this component which considered as an electron-withdrawing groups increase its effectiveness than the other oxopropylthioureas derivatives compared to the reference insecticide.Also, the product 3 gave high effective may be because of the existence of the fluorophenyl p-hydroxy phenyl, carboxalic acid group and piprazin moiety in its chemical structure.In addition to, the insecticidal activity of compound 2 showed higher toxicity might be because of the existence of fluorophenyl, p-methoxyphenyl, carboxalic acid group & piprazin group in its configuration.Finally, compound 8 is higher in toxicity than that of compound 3, 2, 4 & this because of the existence of fluorophenyl & cyanoacetamide in its building.

Experimental
General method for preparing of oxopropylthiourea derivatives 2-10.A solution of target compound 1 (4 mmol) in dry acetone (20 mL), (4 mmol) of amine derivatives, (1 mL) conc.HCl and (0.2gm) anhydrous ZnCl 2 .For roughly 8 h, the reaction mixture was refluxed while being stirred.Ice-cold water was added once then the reaction had been cooled.After being filtered, the solid product was collected and dried.
4 and 5 which represented the insecticidal activity of novel oxopropylthiourea derivatives containing fluorophenyl and cyanoacetamide, we deduced that compound 8 is more efficacious toward second and forth S. littoralis larvae than the other oxopropylthioureas.The present data proved that values of LC 50 of the most effected synthesized compound 8 was 2.412 ppm in which LC 50 for commercial lufenuron was 2.295 ppm.On considering the toxicity line and slope we observed that the slope increase in the following order 8 > 3 > 2 > 6 > 4 > 1 > 9 > 7 > 10 > 5, this order revealed that the homologous response of the treated strain of S. littoralis which presented variation in response against of target synthesized products.Additionally, in an effort to marginally enhance insecticidal compounds, evaluation of the latent effects of the examined components on several biological parameters, including adult longevity, pupal weight, proportion of normal, deformed pupae, & adult emergency, fecundity, & egg hatchability, was carried out.The high in effectiveness of component 8 may be because of the existence of fluorophenyl, cyanoacetamide and carboxalic acid group in their chemical structure.When compared to other oxopropylthioureas derivatives and the commercial lufenuron insecticide, the fluorophenyl and carbonitrile groups, which are thought of as electron-withdrawing groups, boost its efficiency.

the highest toxic biological activity 32 . Toxicological effectiveness checking for adults 4th larvae. After 72 h of treatment, the objective products 1-10 exhibit
). varying degrees of insecticidal efficacy.Their respective LC 50 values for the fourth larvae of S. littoralis were 15.10, 12.78, 10.18, 14.66, 17.68, 13.10, 16.84, 9.531, 16.54, and 16.77 ppm.According of this word, the toxicity of products 2 & 8 toward forth larvae of S. littoralis was nearly lufenuron after seventy two h in which LC 50 value of compounds 8 and 3 was 9.531 and 10.18 ppm and lufenuron was 9.079 ppm.On considering the toxicity line and slope we observed that the slope increase in the following order 8

Table 1 .
Insecticidal effectiveness of components 1-10 & Lufenuron as reference insecticide toward the 2nd & 4th larvae instar of S. littoralis after 3 days of treatment.Notes: Toxicity Ratio is calculated as lufenuron's LC 50 value for baseline toxicity/the compounds' LC 50 value.

Table 2 .
The pupal period with significantly different results from one another, tabulating as 8 (11.32 days) and 3 (13.56days), while 2, 6, and 4 had no significantly different results from one another, tabulating as 14.20, 15.33, and 16.85 days, respectively, compared to the larvae that were not treated (17.34 days).

Table 3 .
The influences of the greatly toxic novelty designing components 2, 3, 4, 6 and 8 at their LC 25 values on the fecundity, fertility & adult longevity for S. littoralis (Boisd.)laboratory strain larvae that survived the fourth instar.Letters mean the noteworthy differences between treatments in line with Duncan's check SE = Standard error.
via filtration.On concerning the data that presented in Table1and illustrated in Figs.