1 Introduction

Spodoptera littoralis is a species of moth in the family Noctuidae and it is a highly polyphagous organism that is a pest of many cultivated plants and crops [1]. Larval phase, of S. littoralis can caused huge and incredible damage to cotton crop in North Africa [2]. Larvae of this pest has minimum seven generations throughout the cotton season, moreover invading more than twenty nine other harvests and plants [3,4,5,6]. To combat the growth of this pest, scientists have improved a variety of organic pesticides [7]. The most challenge is the preparing and presenting an organic compounds which can stop or at least minimize the harmful effect of these pests and at the same time safe to human. It has been reported also that the compounds contain amide or thioamide groups were efficiently control of S. Littoralis and there are many other articles reported a significant use of pesticide materials [8,9,10,11,12,13,14,15,16]. The substitutional controller methods shows foreboding as a prospective method in fall armyworm. The administrative plans are the using of biorational control operators for instance preparing insect growth regulators and those depend on common compounds [17,18,19,20,21,22,23]. Insect growth regulator is improvement controller which is ventured to be more assure for useful living beings than regular mixes, they have been successfully employed in IPM programs in contrast to many plants and little natural materials. There is need to different pesticides which have different modes of action Juvenile hormones analogues, sesquiterpenoid moieties arranged and discharged using of the corpora allata, which important pest hormone compounds that normalize the huge variety of processes through postembryonic growth and adult reproduction in pests [24]. As well as, it improved insecticidal efficacy of a recombinant baculovirus expressing mutated JH esterase from Manduca sexta [25]. In this article, we aimed to report a novel effective S. littoralis cotton pesticides through an easy synthesis of new amides and/or thioamide derivatives and estimate their biological evaluation in contradiction of cotton leafworm.

2 Materials and methods

2.1 Measurements

Melting points of the synthesized compounds were measured on a Fisher-John mechanical tool. Elemental analysis were determined using a Vario EL C, H, N, S analyzer. On a Pye-Unicam SP3-100 spectrophotometer the IR spectra were recorded as potassium bromide disc method. 1H NMR and 13CNMR spectra were produced through Bruker 400 MHz spectrometer using tetramethylsilane (TMS) as a source of perception & concoction movements were justification as ppm. By using a Jeol JMS-400 mass spectra was accomplished. The numbers of Spodoptera littoralis pests were collected from cotton leave worm, fields of Agricultural Research Center, Sohag branch, Egypt.

2.2 Laboratory bioassay

The insecticidal effectiveness of the designed semicarbazide, thiosemicarbazide analogues were saucepan through the leaf dip bioassay methods [26,27,28,29,30,31,32]. The results of laboratory are testified here for the target compounds to find out the required concentrations which are required to kill fifty percentage (LC50) of the 2nd instar larvae & 4th instar larvae of Spodoptera littoralis bugs. In this article, 5 different concentrations of each synthesizing compounds & 0.1% tween 80 as surfactant were employed. Closely the same size ten of 2nd instar larvae & 4th instar larvae bugs where place in disks (nine centimeter diameter) of castor bean leaves which dipped in the checked concentration for 10 s, then left to dry & gave 2nd and 4th larvae, closely of the same size. The larvae were put in glass jars, and every treatment was simulated 3 times (ten larvae per each). Control disks were dipped in dist. H2O and tween 80, then moved to the untreated larvae, which were permitted to feed on castor bean for two days. Impermanence, percentage was recovered after three days for the pesticides. Mortality was redressed by Abbott’s formula [33]. The measurements of the mortality relapse line were dissected by probit analysis [34]. Harmfulness indexes were strongminded through sun equations [35].

3 Results and discussion

3.1 Chemistry

The target compounds, namely, 4-[(phenylcarbamoyl)amino]benzoic acid 2, 4-[(phenyl-carbamothioyl)amino]benzoic acid 3, 4-[(4-oxo-3-phenyl-1,3-thiazolidin-2-ylidene)amino] benzoic acid 4, 4-[(benzoylcarbamothioyl)amino]benzoic acid 5, 4-{[(4-chlorobenzoyl) carbamothioyl]amino}benzoic acid 6, methyl 4-{[(4-chlorobenzoyl)carbamothioyl]amino}benzoate 7 have been successfully synthesized and their structure were established. Thus, reaction of 4-aminobenzoic acid 1 with phenyl isocyanate, phenyl isothiocyanate, benzoyl isothiocyanate and 4-chlorobenzoyl isothiocyanate in dry acetone afforded the desired compounds 2, 3, 5, 6, respectively. However, refluxing the thiourea derivative 3 with chloroacetyl chloride afforded the new 4-[(4-oxo-3-phenyl-1,3-thiazolidin-2-ylidene)amino] benzoic acid 4 via cyclo-elimination manner via losing 2 mol of HCl. Also, esterification of 4-{[(4-chlorobenzoyl) carbamothioyl] amino}benzoic acid 6 with methanol in presence of conc. sulphuric acid led to the new ester compound methyl 4-{[(4-chlorobenzoyl)-carbamo-thioyl]amino}benzoate 7, (Scheme 1).

Scheme 1
scheme 1

Synthesis of Compounds 2–7

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The chemical structures of the products were checked using IR, NMR spectral data, and elemental analyses. The IR spectra of molecules 2, 3, 5, 6 & 7 displayed absorption bands of NH groups around v = 3381–3201 cm−1 and characteristic stretching vibration bands due to carbonyl groups at v = 1716–1644 cm−1, respectively. Whereas, the absorption of NH groups completely disappeared in the IR spectrum of 1,3-thiazolidine derivative 4 confirming the cylization of compound 3. Also, the 1HNMR spectra of compounds 2, 3, 5, 6 and 7 revealed singlet signals at about δ = 11.04–8.02 ppm characteristic for the 2NH groups, which clearly did not recognized in the 1H NMR of 1,3-thiazolidine derivative 4, which showed instead a singlet at δ = 4.30 ppm characteristic of the CH2 group. Another evidence for formation of compound 4 comes from its 13CNMR spectrum which showed an absorption at δ = 15.60 and at δ = 188.5 ppm assigned for methylene and carbonyl carbons of 1,3-thiazolidine ring, respectively.

A plausible mechanism may suggested to rationalize the formation of 1,3-thiazolidine derivative 4 as shown in chart 1. Thus, a primary nucleophilic attack of 4-aminobenzoic acid into aryl isothiocyanate lead to the thiourea derivative 3a. Then, the free electrons of imino (NH) and thiol (SH) functions of 3a/3b attacks of chloroacetyl chloride to yield 4-[(4-oxo-3-phenyl-1,3-thiazolidin-2-ylidene)amino] benzoic acid 4 via cyclization to 3c followed by elimination of 2 mol of HCl to give 1,3-thiazolidine derivative 4.

Chart 1
figure 1

Suggested mechanism for compound 4

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As well as, the 2-(4-chlorobenzoyl)-N-phenylhydrazinecarboxamide 9, 2-(4-chlorobenzoyl)-N-phenylhydrazine carbothioamide 10, N-phenyl-2-(pyridin-2-ylcarbonyl)hydrazinecarboxamide 11, N-phenyl-2-(pyridin-2-ylcarbonyl)hydrazinecarboxamide 12, N-phenyl-2-(pyridin-2-ylcarbonyl)-hydrazine-carbothioamide 13 were successfully synthesized and established (Scheme 2).

Scheme 2
scheme 2

Synthesis of Compounds 9–13

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3.2 Experimental

3.2.1 General process for designing of products 2–7

4-[(Phenylcarbamoyl)amino]benzoic acid 2, 4-[(phenylcarbamothioyl)amino]benzoic acid 3, 4-[(benzoylcarbamothioyl)amino]benzoic acid 5, 4-{[(4-chlorobenzoyl)carbamothioyl]amino} benzoic acid (6) were synthesized in analogy to the procedure described in literature [36, 37].

Refluxing of equimolar amounts of 4-aminobenzoic acid and each of phenyl isocyanate, phenyl isothiocyanate, benzoyl isothiocyanate, 4-chlorobenzoyl isothiocyanate, respectively in dry acetone for 3 h, and the reaction was monitored by TLC affording 2, 3, 5 and 6, respectively. Also, compound 4-[(phenylcarbamothioyl)amino]benzoic acid 3 was boiled with chloroacetyl chloride for 1 h. under reflux gave 4-[(4-oxo-3-phenyl-1,3-thiazolidin-2-ylidene)amino] benzoic acid 4. Then the reaction mixture was concentrated, the precipitation compound had been collection through filtration, washed thoroughly with ethyl alcohol, dried and purification through crystallization from absolute ethyl alcohol. However, methyl-4-{[(4-chlorobenzoyl)carbamothioyl]amino}benzoate 7 was obtained via esterification of compound 4-{[(4-chlorobenzoyl) carbamothioyl]amino}benzoic acid 6 via refluxing with methanol in presence of Conc. sulfuric acid the solution for 60 min, the reaction combination allowed to transfer on icy H2O, the formed precipitation had been collection via filtration, washing with H2O, dried & purification by crystallization in absolute ethanol.

4-[(Phenylcarbamoyl)amino]benzoic acid (2): Gray powder (83% yield); melting point; 185 ℃; IR (ν−, cm−1): 3308 (OH), 3192 (NH), 3058 (CHarom), 1667 (C = O), 1644 (C = O), 1592 (C = C). 1HNMR (DMSO-d6), (δ ppm): 12.65 (OH), 9.08 (s-1H-NHexch), 8.81 (s-1H-NHexch), 7.92–7.55 (m, 9H, Harom); 13CNMR: 167.55, 154.2, 152.70, 144.49, 140.17, 139.81, 139.70, 131.72, 131.32, 131.04, 130, 129.57. Anal. for C14H12N2O3: Calcd. /found C:65.3/65.6, H: 7.2/7.4 and N: 10.91/10.93%.

4-[(Phenylcarbamothioyl)amino]benzoic acid (3): Browne crystals (85% yield), melting point; 169 ℃; IR (ν−, cm−1): 3201 (NH), 3118 (NH), 3009 (CHarom), 1685 (C = O), 1594 (C = C). 1HNMR (DMSO-d6), (δ ppm): 12.67 (OH), 10.72 (s, 1H, NHexch), 9.76 (s, 1H, NHexch), 7.97–7.39 (m, 9H, Harom).13CNMR: 189.22, 179.97, 167.43, 129.87, 128.99, 128.91 126.62, 119.23, 117.54, 113.19. Anal. for C14H12N2O2S: Calcd./found C: 61.72/61.75, H: 4.41/4.44 and N: 10.29/10.27%.

4-[(4-Oxo-3-phenyl-1,3-thiazolidin-2-ylidene)amino]benzoic acid (4): Browne crystals (80%yield), melting point; 200 ℃. IR (ν−, cm−1): 3411 (OH), 3111 (CHarom), 1718 (C = O), 1608 (C = N); 1HNMR (DMSO-d6), (δ, ppm): 11.42 (s, 1H, OH), 7.93–7.14 (m, 9H, Harom), 4.30 (s, 2H, CH2). 13CNMR: 188.05, 167.26, 165.90, 145.14, 144.61, 144.22, 131.40, 130.70, 129.58, 128.35, 15.60. Anal. for C16H12N2O3S Calcd/found: C: 61.53/61.52, H: 3.87/3.85 and N: 8.97/8.95%.

4-[(Benzoylcarbamothioyl)amino]benzoic acid (5): Yellow powder (84% yield), melting point 210 ℃. IR (ν−, cm−1): 3335 (NH), 3272 (NH), 3163 (CHarom), 1716 (C = O), 1677 (C = O), 1589(C = C); 1HNMR: 11.09 (s, 1H, OHexch), 11.04 (s, 1H, NH), 8.05–7.56 (m, 10H, Harom + NH). Anal. for C15H12N2O3S Calcd/found: C: 599.99/59.97, H: 4.03/4.01 and N: 9.33/9.30%.

4-{[(4-Chlorobenzoyl)carbamothioyl]amino}benzoic acid (6): Grey powder (80% yield), melting points; 213 ℃. IR (ν−, cm−1): 3302(NH), 3062 (CHarom), 1673 (C = O),1588 (C = C); 1HNMR (DMSO-d6), (δ ppm): 12.88 (s, 1H, OH), 10.55 (s, 1H, NH), 8.01–7.56 (m, 9H, Harom + NH); 13CNMR: 167.40, 166.94, 165.38, 143.49, 138.28, 137.28, 133.77, 131.59, 131.10, 130.67, 129.18, 128.98, 126.21, 123.99, 120.12, 113.11. Anal. for C15H11ClN2O3S Calcd/found: C: 53.82/53.79, H: 3.31/3.28 and N: 8.37/3.35%.

Methyl 4-{[(4-chlorobenzoyl)carbamothioyl]amino}benzoate (7): Grey powder (74% yield), melting point; 245 ℃. IR (ν−, cm−1): 3381 (NH), 3046(CHarom), 2922(CHalph) 1701 (C = O), 1606 (C = C). 1HNMR (DMSO d6), (δ ppm):8.02(s, 2H, NHexch), 7.99–7.04 (m, 9H, Harom), 2.61 (s, 3H, CH3). 13CNMR: 167.67, 166.99, 149.48, 138.26, 131.59, 129.20, 120.69, 115.66, 50.83(CH3). Anal. for C16H13ClN2O3S Calcd/found: C: 55.09/55.06, H: 3.76/3.74 and N: 8.03/8.01%.

3.2.2 General procedure for synthesizing of compounds 9–13

A solution of phenylisocyanate 8a or phenylisothio cyanate 8b (30 mmol) in 15 ml acetone was added to (30 mmol) of hydrazide derivatives (4-chlorobenzhydrazide, 2-naphthohydrazide and 2-hydrazinopyridine) & refluxing for three to four hours. After finishing reaction time (tested by then layer chromatography) solution moved into icy water, the subsequent products were collecting by filtration, washing thoroughly with H2O & crystallization using CH3CH2OH/ClCH2CH2Cl mixture (1:1).

2-(4-Chlorobenzoyl)-N-phenylhydrazinecarboxamide (9): Yellow powder (83% yield) melting point; 214 ℃; IR (ν−, cm−1): 3295 (NH), 3097 (CHarom), 1667 (C = O), 1633 (C = O), 1596 (C = C). 1HNMR (DMSO-d6), (δppm): 10.35 (s, 1H, NHexch), 8.83 (s, 1H, NHexch), 8.18 (s, 1H, NHexch) 7.96–6.97 (m, 9H, Harom). 13CNMR: 166.12, 156.51, 156.0, 139.95, 137.13, 131.80, 129.92, 129.12, 128.97, 122.55, 119.19. Anal. for C14H12ClN3O2 Calcd./found: C:58.04/58.01, H: 4.17/4.13 and N:14.50/14.49%.

2-(4-Chlorobenzoyl)-N-phenylhydrazinecarbothioamide (10): Brownish solid (89% yield), melting point; 140 ℃; IR (ν−, cm−1): 3296, 3184, 3147 (3 NH), 3104 (CHarom), 3005 (CHarom), 1637 (C = O), 1601 (C = C); 1HNMR (DMSO-d6), (δ ppm): 10.51 (s, 1H, NHexch), 9.80 (s, 1H, NHexch), 9.67 (s, 1H, NHexch), 7.99–7.15 (m, 10H, Harom); 13CNMR: 182.30, 166.47, 148.7, 139.84, 133.21, 132.5, 132.16, 129.84, 129.20, 128.65, 127, 126, 125, 124, 116, 114. Anal. for C14H12ClN3OS Calcd./found: C:54.99/54.96, H:3.96/3.93, and N:13.74/13.71%.

2-(Naphthalen-2-ylcarbonyl)-N-phenylhydrazinecarboxamide (11): Grey crystal (70%yield), melting point; 220 ℃. IR (ν−, cm−1): 3294 (NH), 3220 (NH), 3136 (NH), 3090 (CHarom), 1704 (C = O), 1667 (C = O), 1595 (C = C). 1HNMR (DMSO-d6), (δ ppm): 12.51 (s, 1H, NHexch), 11.23 (s, 1H, NHexch), 7.97–7.59 (m, 12H, Harom). 13CNMR: 185.4 (C = O), 179.6 (C-NH), 155.4(C–CO), other aromatic C-H carbons at 142.2, 140.2, 132.3, 130, 128.8. Anal. for C18H15N3O2 Calcd/found: C: 70.81/70.78, H: 4.95/4.92 and N: 13.76/13.74%.

N-Phenyl-2-(pyridin-2-ylcarbonyl)hydrazinecarboxamide (12): Grey powder (76%yield), melting point; 201 ℃. IR (ν−, cm−1): 3343 (OH), 3318 (NH), 3272 (NH), 3151 (NH), 3104 (CHarom), 3055 (CHarom), 1718 (C = O), 1650(C = O), 1616(C = N), 1598 (C = C). 1HNMR (DMSObd6), (δppm): 10.50(s, 1H, NHexch), 8.85 (s, 1H, NHexch), 8.05(s, 1H, NHexch), 7.46–7.26 (m, 9H, Harom). 13CNMR: 165.9, 158, 150, 149 (C–CO), 140, 139, 130, 129.8, 126, 125, 119. Anal. for C13H12N4O2 Calcd/found: C: 60.93/60.90, H: 4.72/4.70 and N: 21.86/21.83%.

N-Phenyl-2-(pyridin-2-ylcarbonyl)hydrazinecarbothioamide (13): Yellow powder (56% yield), melting point; 270 ℃. IR (ν−, cm−1): 3297 (NH), 3234 (NH), 3205 (NH), 3046 (CHarom), 1653 (C = O), 1593 (C = C); 1HNMR (DMSO-d6), (δ, ppm): 10.68 (s, 1H, NHexch), 9.71 (s, 1H, NHexch), 8.70 (s, 1H, NHexch), 8.69–7.13 (m, 9H, Harom).13CNMR: 181.12, 181, 149.74, 148.99, 139.69, 138.18, 128.52, 127.42, 125.31, 122.91. Anal. for C13H12N4OS Calcd/found: C: 57.34/57.31, H: 4.44/4.41 and N: 20.57/20.54%.

3.3 Insecticidal bio-efficacy screening

The objective designed compounds have been tested as pesticide bioefficacy for explanation as following:

3.3.1 Toxicological effectiveness checked for of 2nd instar larvae of Spodoptera littoralis after three days of treatment

After 3 days of treatment, bioefficacy results for the designed Semicarbazide, Thiosemicarbazide, Urea and Thiourea derivatives 2–7 and 9–13 showed height to low toxicological activity against S. littoralis and the results are listed in Table 1. It has been notice that the LC50 values vary from 9.882 to 102.3, in which LC50 value of compounds 2–7 and 9–13 were 73.69, 45.10, 85.67, 59.88, 17.56, 9.88, 21.32, 54.25, 93.39, 102.3 and 96.35 ppm, respectively in which dimilin 5.946 ppm. The toxicity of chloro ester compound 7 was the most toxicological activity against 2nd instar larvae of Spodoptera littoralis than the other synthesized urea and thiourea compounds and its toxicity ratio at 1.0 with LC50 value at 102.3 ppm, followed by its source benzoic acid derivatives 6 which clearly render to the vital role played by chlorine atom attached to aromatic ring.

Table 1 Insecticidal effectiveness of compounds 2–7, 9–13 & dimilin as reference insecticide against the 2nd instar larvae and 4th instar larvae of Spodoptera Littoralis after 72 h of treatment
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3.3.2 Toxicological effectiveness test for 4th instar larvae of Spodoptera littoralis after 72 h of treatment

The bioefficacy outcomes of compounds 2–7 and 9–13 against 4th instar larvae of S. littoralis are displayed in Table 1. After three days of treatment, bioefficacy outcomes showed LC50 values of compounds 2–7 and 9–13 at 164.01, 122.48, 151.08, 163.66, 111.09, 102.66, 119.36, 153.30, 166.35, 172.86 and 158.36 ppm, respectively in which dimilin 59.914 ppm. These results again confirm that the toxicity of compound 7 against 4th instar larvae of S. littoralis is the most active among the other tested compounds because LC50 value of compound 7 is 102.66 ppm and its toxicity ratio at 1.0. Again, the role played by the chlorine atom in both acid and its ester derivative is the reason for their high potency.

4 Structure-action relationship (SAR)

The results listed in Table 1 and Figs. 1, 2 showed that although the main frame structure of the designed compounds is the thiourea and its derivatives, but the existence of chlorine atom linked to the aromatic cycle may the main reason for the high activity recorded for compounds 7, 6 and 9, respectively against 2nd instar larvae and 4th instar larvae of S. littoralis. Meanwhile, the esterification of benzoic acid derivative 6 to give the ester compound 7 render it more potent and high toxic than the acid 6. Also, it is noteworthy that we expect that the presence of pyridine ring as in compound 12 will showed a good activity, unfortunately, it has not remarkable toxic effect as it notice as antibacterial and antifungal. As well as, the 1,3-thiazolidine derivative 4 showed low activity.

Fig. 1
figure 2

Insecticidal activity of compounds 2–7, 9–13 and Dimilin as reference insecticide against the 2nd instar larvae and 4th instar larvae of Spodoptera littoralis after 3 days of treatment

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Fig. 2
figure 3

Insecticidal activity of compounds 2–7, 9–13 and dimilin as reference insecticide against the 2nd instar larvae and 4th instar larvae of Spodoptera Littoralis after 72 h of treatment

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5 Conclusion

A series of Semicarbazide, Thiosemicarbazide derivatives have been prepared and confirmed based on spectral and elemental analyses. The toxicity of these compounds were projected against S. Littoralis (Lepidoptera: Noctuidae) & illustrated that a number of the designed compounds have respectable toxicological effectiveness as pesticides. Specifically, compound 7 which has the best insecticidal effectiveness against 2nd instar larvae and 4th instar larvae of S. littoralis than the other designed derivatives. The activity regarding compound 7 may be due to the presence of the chlorophenyl, mehtoxy groups in addition to thiourea nucleus linked to molecular structure. These results are encouraged and appreciated for additional work on the development of novel and other strong insecticides. Our work established that the urea and thiourea derivatives could effectively control against 2nd instar larvae & 4th instar larvae of S. littoralis.