Synthesis and Bioevaluation of 3-( substitutedphenyl )-1-( 4-hydroxyphenyl )-2-propen-1-ones and their Carbamate Derivatives against Root-Knot Nematode ( Meloidogyne javanica )

Synthesis of 3-(4-chloro/methyl/nitro/methoxy/3,4,5-trimethoxy/2,4-dichloro/ 4-bromo/ 3, 4-dimethoxy/ 2, 4-dimethoxy/ 3-bromo/ 2-chloro/ 2-methoxy phenyl)-1-(4-hydroxyphenyl)-2-propen-1one (14-25) has been carried out from substituted benzaldehyde (1-12) and 4-hydroxy acetophenone (13). The condensation of synthesized 2-propen-1-ones (14-25) with phenyl isocyanate (26) gave 4-[3-(4-chloro/ methyl/nitro/methoxy/3, 4, 5-trimethoxy/2, 4-dichloro/4-bromo/3, 4-dimethoxy/2, 4-dimethoxy/3-bromo phenyl) prop-2-enoyl] phenyl phenylcarbamate (27-36). The synthesized compounds were characterized on the basis of analytical and spectral data. All the compounds were evaluated for their nematicidal activity invitro against second stage juveniles (J2) of root knot nematode (Meloidogyne javanica). Incorporation of carbamoyloxy moiety in 2-propen-1-ones enhanced the activity. Irrespective of the concentration, compounds 3-(4-methoxyphenyl)-1-(4hydroxyphenyl)-2-propen-1-one (17) and 4-[3-(4-methoxyphenyl) prop-2-enoyl] phenyl phenyl carbamate (30) have shown maximum nematode mortality i.e. 30% and 51.8%.

Carbamates as a class are not generally persistent in the environment 3 .Carbamates are effective nematicides by virtue of their ability to inhibit acetyl cholinesterase (AchE) in the nervous system and thereby, disrupt nervous transmission at that location 4 .In view of the diverse type of biological activities shown by carbamates, their importance as agrochemicals and as a part of our ongoing new nematicide development programme [5][6][7] , it was thought of interest to synthesize and evaluate nematicidal activity of substituted 4- [3-(substitutedphenyl) prop-2-enoyl]phenyl phenyl carbamates.

EXPERIMENTAL Materials & Methods
The melting points were determined in open capillaries on a Ganson electrical melting point apparatus and are uncorrected.Homogeneity of the compounds was routinely checked on silica gel-G TLC plates using ethyl acetate: hexane (3:7) as irrigant.IR spectra were recorded on "Perkin Elmer FTIR" spectrophotometer in KBr and frequencies are expressed in cm -1 .The NMR spectra were recorded on "Bruker AC-400-F" (400MHz) NMR spectrophotometer in CDCl 3 or DMSO-d 6 using tetramethylsilane (TMS) as internal reference.The chemical shift values are expressed in ´ (ppm) units while J values in Hz and are compatible with the assigned structures.The elemental analyses were within ± 0.4 % of that of evaluated values.Only those spectral data have been mentioned which have a direct bearing on the assignment of the structures and are discussed here.
Stock solutions of 2000mg L -1 of all the compounds were prepared by dispersing these in acetone.
Nematicidal activity was evaluated against second stage juveniles (J 2 ) of M. javanica.A suspension of juveniles (1 ml) was poured into 5cm Petri-dishes.Measured quantities of stock solution were added to these Petri-dishes to make final concentrations of 1000, 500, 250 and 125 ppm.Acetone with water was used as control.No nematode mortality was recorded in these controls, and is therefore not included in the table.Each treatment was replicated three times.These Petri-dishes were kept in a BOD incubator at 28±1°C.Observations were recorded after 24h and 48h by counting live (active) and dead (inactive) J 2 s under a stereoscopic binocular microscope and the per cent mortality was counted 10 .The revival of immobilized nematodes was examined by randomly transferring ten J 2 s to water for 24 h.None of those immobilized J 2 s revived.The experimental data was statistically analyzed using two factorial completely randomized design; the compounds and the concentrations constituting the two factors.
The 1 HNMR spectra of 14-25 were in accordance with the proposed structures.The substituted-2-propen-1-ones were found to possess E-configuration, which is confirmed on the basis of their 1 H NMR spectra.The diagnostic olefinic protons (-CO-CH=CH-) attached to carbonyl functionality appeared as clean doublets at around 7.42 and 7.67 δ (each with J= 16.0 Hz), situated at α and β respectively and this confirms the condensation of the reactants.Methyl, methoxy and trimethoxy  ´ integrating for two protons (J=8.0Hz) was observed, which confirm the two aromatic protons of C 3 and C 5 positions (ortho to chloro) respectively.The two diagnostic doublets (J=16.0Hz) could be assigned at 7.42 ´ and 7.74

Scheme 2: Synthesis of 4-[3-(substitutedphenyl)prop-2-enoyl]phenyl phenyl carbamates
´ respectively for -CO-CH=CH-protons (± and ² to keto) was indication of two olefinic protons.A doublet integrating for two protons with J=8.0Hz was observed at 7.67 ´ for C 3 ' & C 5 ' respectively while C 2 and C 6 protons were picked up as doublet at 7.69 δ (J=8.0Hz).A methoxy group was observed as singlet at 3.83 δ and all other protons at their usual positions in 3-(4-methoxyphenyl)-1-(4-hydroxyphenyl)-2propen-1-one (17) supported the assigned structure.Appearance of peaks near 1680 cm -1 and 3300 cm -1 for C=O stretching and OH functionality, in the IR spectra of the above compounds further corroborated their structures.In the next step of synthesis, condensation of compounds 3-(4-chloro/ methyl/ nitro/ methoxy/ 3,4,5-trimethoxy/ 2,4-dichloro/ 4-bromo/3,4dimethoxy/2,4-dimethoxy/3-bromo phenyl)-1-(4-hydroxy phenyl)-2-prop-1-one (14-25) with phenylisocyanate (26) in equimolar ratio in dry benzene by refluxing on steam bath for 12 h, afforded their corresponding 4 Another two doublets at 7.38 ´ and 7.55 ´ integrating for two protons each were assigned to protons at positions C 3 ' and C 5 ' or C 2 and C 6 respectively.The downfield shift of C 2 ' and C 6 ' protons ortho to carbonyl functionalities appeared at 7.66 δ.The remaining aromatic protons appeared as multiplet at 7.66 δ to 7.55 δ.The broad singlet at 8.50 δ was assigned to NH proton of carbamoyloxy moiety.The formation of carbamates of the above compounds follows from the mode of synthesis and were supported by the appearance of a band around 3340 cm -1 for NH functionality and around 1670 and 1690 cm -1 for carbonyl and carbamoyloxy (C=O) functionalities respectively.Thus, structures of all these compounds were fully supported by their NMR and IR spectra.
In general, nematoxicity increased with time.Among these compounds no significant difference was recorded after 48h.Compound 17, 22 and 21 exhibited highest toxicity at 1000ppm and compound 14, 18, 16 and 19 showed least