Preparation and biological activity evaluation of some benzoylthiourea and benzoylurea compounds

Due to the complicated problems coming from excessive applications of insecticides

Due to the complicated problems coming from excessive applications of insecticides, searching for safe substitutes to these insecticides has become a necessity. Thus, the insect growth regulators are candidates to be used in such concern. Comparative studies of the effects of three compounds, 2-benzoyl-N-phenylhydrazine-1-carbothioamide (1), 2-(cyanoacetyl)-Nphenylhydrazine-1-carboxamide (2) and N- (2-(2-cyanoacetyl)hydrazinecarbonothioyl)furan-2carboxamide (3) (an insect growth regulator inhibiting chitin synthesis), were conducted on Spodoptera littoralis (Boisduval, 1833). The compounds, orally administered, caused larval mortality proportional to the concentrations in the food source. larvae were unable to complete the molting process and died in the old larval cuticle. Larvae contaminated by sublethal doses completed their development to adulthood. N- (2-(2-cyanoacetyl)hydrazinecarbonothioyl)furan-2-carboxamide (3) is more active than the other compounds have LC50 17.082 ppm for 2 nd instar larvae and 60.832 ppm for 4 th instar larvae.

Introduction
Organic compounds are very important in nature due to their different applications. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Urea and Thiourea its derivatives constitute an important class of heterocyclic compounds which possess wide range therapeutic and pharmacological properties. Sulphonylureas become widely available in 1955 for the treatment of non-ketosis mild diabetes and are still being the drugs of choice. 18 Benzoylurea and benzoylthiourea insecticides have many attractive properties such as high selectivity, 19 high biological activity, rapid degradation in soil and water and the acute low toxicity for animals, which make them suitable for inclusion in integrated pest management programs for crops. 20 On the other hand, many Urea and Thiourea compounds have been developed into insecticide, fungicides, insecticides and other agricultural chemicals. 21 IGRs include juvenile hormone (JH), mimic and chitin synthesis inhibitors (CSIs). 22 CSIs, such as hexaflumuron, lufenuron and diflubenzuron, which inhibit the production of chitin, a major component of the insect exoskeleton. Insects treated with CSIs become unable to synthesize new cuticle, and therefore unable to successfully molt into the next stage. 23 CSIs may be toxic to other arthropods, and IGR metabolites may have adverse effects on vertebrates due to their ability to bind to certain members of the nuclear hormone receptor family. 24 The benzoylurea constitute a class of the IGRs that interfere with insect growth and development by inhibiting chitin synthesis in insects. 25 The cotton leafworm Spodoptera littoralis (Boisd.) is a major polyphagous key pest in Egypt. It has been well established that diflubenzuron (DFB) inhibits chitin synthesis in vivo and that such action constitutes the main insecticidal mechanism of this compound. However, the precise molecular mechanism of its action has not been elucidated. 26

Chemistry
Following our project in preparation and toxicity evaluation of juvenile hormones analogues, here we prepared three compounds that are shown in Fig. 1. The three compounds, namely, 2-benzoyl-Nphenylhydrazine-1-carbothioamide 1, 2-(cyanoacetyl)-N-phenylhydrazine-1-carboxamide 2 and N-(2-(2-cyanoacetyl)hydrazinecarbonothioyl)furan-2-carboxamide 3 were prepared as follow: Compounds 1 and 2 were prepared according to the reported methods. 27,28 In addition to the procedure reported before, 29 compound 3 was synthesized here by reaction of furan-2-carbonyl chloride with ammonium thiocyanate that gave furan-2-carbonyl isothiocyanate which reacted with 2-cyanoacetohydrazide to give compound 3. Spectroscopic data and elemental analyses of compound 3 were in agreement with its proposed structure.

Insecticidal activity of compounds 1, 2, and 3.
The objective tested compounds have been used for insecticidal activity as explained beneath: As shown in Table 1, target compounds were tested of their activity as insecticides in which shown beneath. Three previously mentioned compounds displayed strong to weak toxic action against the 2 nd instar larvae in light of the fact that various of them were active after 72 hr. of the test LC50 values of compounds 1, 2 and 3 were 73.125, 26.635 and 17.082 ppm, respectively.
As shown in Table 1, target compounds were tested for their activity as insecticides and this is shown beneath. three previously mentioned compounds displayed strong to weak toxic action against the 4 th instar larvae after 72 hrs of the treatment in which LC50 values changed from 103.125 to 145.908 ppm for compounds 1 and 2 while compound 3 LC50 was 60.832 ppm.

Conclusion
A chain of benzoylthiourea and benzoylurea which are analogues to insect growth regulators in which contain cyano group were chemically synthesized. The toxic activity of the tested target compounds was assessed against 2 nd and 4 th instar larvae demonstrated that some of the synthesized target compounds have great toxicological activity, though some of them uncovered sensible aphicidal activity. Particularly, compound 3 was the most toxic action since it surpassed the aphicidal activity of a refrance insect growth regulators. The activity concerning compound 3 might be because of the presence of the cyano and fuoryl group joined to the atomic structure.

Materials and methods
All melting points are uncorrected and were determined by Kofeler melting point apparatus. IR (cm -1 ) spectra were recorded (KBr disc) on a Shimadzu DR-8001 spectrophotometer. 1 HNMR (DMSO-d6) spectra were recorded at 200 MHz on a Varian Gemini NMR spectrometer and also at 400 MHz, the chemical shift is expressed in δ value (ppm) using TMS as an internal reference. All NH groups were subjected to hydrogen/deuterium exchange test. Elemental analyses were carried out on a Perkin-Elmer 240°C Micro analyzer. The mass spectra were performed on Micro mass 7070E spectrometer using Direct Inlet and Shimadzu Qp-2010.

Laboratory bioassay
The method that measures toxicity of the target compounds was tested by leaf dipping bioassay. Results of research facility screening to discover the suitable concentrations of the objective target compounds which are deformation in the insect to kill half 50 % LC50 of instar larvae were proclaimed here. Five concentrations of arrangement of each synthesized compound in addition to 0.1 % Triton X-100 as a surfactant were used. The number of ten 2nd instar larvae and 4th instar larvae of insects, nearly have the same size, plates (9 cm. distance across) of castor bean leaves in which dunked in the objective treatment concentrations for 10 s then left to dry and offered to larvae, which starved for 46 treatment was reproduced multiple times (10 larvae for each). Control was dunked in distilled water only. The larvae were permitted to benefit from treated plates for 48 h., then transferred to the untreated ones. Mortality percentages were recorded after 72 h. for all insecticides. Mortality was redressed by Abbott's formula. 30 The doses mortality relapse lines were statistically investigated by probit analysis. 31 Toxicity Index and Relative Potency determined by Sun equations. 32 Slope esteems and middle deadly focused concentrations LC50 of the title target compounds were determined through a Probit relapse investigation program and recorded in (ppm). Were inundated for 10s in each concentration multiple times (3 times). Pests which were treated were left to dry at room temperature for about half hour. Control clumps of utilized pests were likewise used. The insecticidal action trial of each compound was rehashed multiple times (2 times) and the obtained data were rectified by Abbott's equation. By utilizing a modernized probit relapse investigation program, middle deadly fixations (LC50) and incline estimations of objective target compounds were figured and revealed as (ppm).