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Context: Imaging the mutation status of non-small cell lung cancer (NSCLC) using radiolabeled tyrosine kinase inhibitor (TKI) analogs has garnered interest due to their unique interactions with the target epidermal growth factor receptor (EGFR). Rociletinib is a third-generation TKI that selectively inhibits the activated EGFR L858R/T790M mutations while sparing the wild-type EGFR. Aims: To synthesize a rociletinib analog for radioiodination purposes and evaluate its affinity for EGFR L858R/T790M using molecular docking and in vitro cytotoxicity assay. Methods: The rociletinib analog, N-{3-[(4-{[4-(4-acetylpiperazin-1-yl)-2-methoxyphenyl]amino}-5-(trifluoromethyl)pyrimidine-2-yl)amino] -5-iodophenyl} acrylamide (I-RMFZ), was produced by adding iodine into the diaminophenyl group and changing the position of the trifluoromethyl group. A simulation of molecular docking was conducted using the AutoDock Vina software suite. IC50 of I-RMFZ was determined using a cell cytotoxicity assay. Results: I-RMFZ was successfully synthesized through multistep reactions. Molecular docking revealed that I-RMFZ interacts with the EGFR L858R/T790M mutation. Cytotoxicity assay demonstrated that I-RMFZ had a high selectivity towards EGFR L858R/T779M mutation. Conclusions: I-RMFZ is notable for radioiodination and is anticipated to be comparable with in vivo features of rociletinib. Thus, I-RMFZ can potentially be developed as an imaging agent for NSCLC through preclinical assay.

The nitrovanillin azine (NA) has been successfully synthesized and examined as a colorimetric chemosensor for sulfide anion detection. The NA was synthesized using two steps reaction. Vanillin was reacted with concentrated nitric acid to form 5-nitrovanillin (NV) then the NV was condensed with hydrazine hydrate to produce the NA. The NA was obtained and fully elucidated by FTIR, 1H-NMR, 13C-NMR, and GC-MS spectrometer. The NA activity for anionic chemosensor was then carried out on several anions such as F⁻, Cl⁻, Br⁻, I⁻, S2⁻, CN⁻, HCO3⁻, AcO⁻, H2PO4⁻, N3⁻, NO2⁻, SCN⁻, ClO3⁻, and NO3⁻. The chemosensor tests showed NA was only selective for S2− in DMF:HEPES buffer (9:1, v/v, 10 mM, pH = 7.4) giving color change from light yellow to dark green. The LOD value was 1.43 × 10−5 M and the interaction model of NA-S2− indicated deprotonation mode between the -OH group with sulfide anion in a ratio of 1:1. The NA chemosensor can be applied for qualitatively analysis of sulfide anion using filter paper strips and quantitatively analysis of sulfide anion in tap water.

Vanillin-azine (VA), (4,4'-((1E,1'E)-hydrazine-1,2-diylidenebis(methane-lylidene))bis(2-methoxyphenol) has been synthesized from vanillin and tested as anion colorimetric chemosensors for sulfide anion. The VA was obtained from a condensation reaction between vanillin and hydrazine hydrate with a mol ratio of 2:1 mol for 24 h at room temperature. The structure was elucidated using FTIR, GC-MS, 1H-NMR, and 13C-NMR spectrometers. The VA compound was examined as a colorimetric chemosensor for sulfide anion over several anions of CN−, F−, Cl−, Br−, I−, N3−, CH3COO−, and NO3−. The structure of the product showed agreement with all spectrometric data. The VA chemosensor tests indicated only selective to S2− anion followed by a color change from colorless to light blue in a DMF:HEPES buffer solution (DMF:HBS) medium (9:1, v/v, 10 mM, pH = 7.4). Filter paper strips can detect S2− anion with a color change from white to yellow. The VA chemosensor has a limit of detection (LOD) of 5.4 × 10−4 M, therefore, the VA chemosensor can be applied to detect S2− anion in tap water.

Recently, biodiesel production from palm oils has been thoroughly investigated to substitute crude oil due to its scarcity. However, the biodiesel production process is time-consuming due to its slow kinetics; thus, concentrated sulfuric acid has been used to fasten the reaction process in some industries. Unfortunately, sulfuric acid is a toxic, corrosive, and non-environmentally friendly catalyst. In this study, we prepared sulfated Calix[4]resorcinarene derived from vanillin as an efficient organocatalyst to replace sulfuric acid. The catalytic activity of sulfated Calix[4]resorcinarenes was evaluated through the methylation of palmitic acid and oleic acid as model compounds due to their abundant amounts in palm oil. The Calix[4]resorcinarene and sulfated Calix[4]resorcinarenes have been obtained through a one-pot reaction in 71.8–98.3% yield. Their chemical structures were confirmed by using FTIR, NMR and HRMS spectrometry analyses. The results showed that the sulfated Calix[4]resorcinarene exhibited high catalytic activity for methyl palmitate and methyl oleate productions in 94.8 ± 1.8 and 97.3 ± 2.1% yield, respectively, which was comparable to sulfuric acid (96.3 ± 1.8 and 95.9 ± 2.5%). The optimum condition was achieved by using 0.020 wt equivalent of organocatalyst for 6 h reaction process at 338 K. The methylation of palmitic acid and oleic acid fits well with the first-order kinetic model (R2 = 0.9940–0.9999) with a reaction rate constant of 0.6055 and 1.1403 h-1, respectively. Further investigation reveals that the hydroxyl group of vanillin plays a pivotal role in the organocatalytic activity of sulfated Calix[4]resorcinarene.

Anthocyanins as chemosensory compounds for amines have been tested in this study. Because anthocyanins are sensitive to pH changes, while amines have an alkaline nature, they can cause structural changes in anthocyanins, resulting in changes in the color of anthocyanins. The source of anthocyanins was the Kepok banana bracts (Musa paradisiaca L.), which were extracted using a mixture of ethanol:HCl 0.15% (3:2). The types of anthocyanin compounds were characterized using a UV-Vis spectrophotometer. The anthocyanin content obtained varied from 1.26 mg/100 g to 5.08 mg/100 g. The type of anthocyanin in the Kepok banana bracts was found as a cyanidin-3-rutinoside with maximum absorption at 513 nm at pH 1. The color of anthocyanin extract varied with changes in pH; it turned red in acid and faded in neutral solutions. The green color in the alkaline solution changes to brownish-yellow was associated with anthocyanin degradation. The color change at different pH indicates that banana bracts are regarded as a potential chemosensory compound to detect tuna freshness. The chemosensor was applied to a cellulose-based strip and exhibited a color change that corresponded to the increase in pH and was comparable to the results of the pH meter measurement. The structural changes of anthocyanin before and after the tuna freshness test were identified by the FTIR-ATR, indicating a change in the anthocyanin structure. Tuna freshness began to diminish after being stored for 12 and 24 hours at room temperature, marked by a color change of the paper strip to colorless and blackish gray.

Cyanide is a highly toxic anion and poison to the environment. Therefore, fast, effective, and efficient analysis methods to detect cyanide are needed. Herein, symmetrical chemosensor of 2’-hydroxy acetophenone azine (1) and 2’,4’-dihydroxy acetophenone azine (2) has been synthesized tested as colorimetric and fluorescent cyanide chemosensor. The azines were produced from the condensation of acetophenone derivatives with hydrazine hydrate in ethanol under reflux or ultrasonic irradiation methods. Colorimetric and fluorescent chemosensor tests showed selectivity to acetate and cyanide anions in DMSO. The limit of detection (LOD) for colorimetric measurement of cyanide anion was 9.68×10–4 M for compound (1) and 9.63×10–5 M for compound (2), while the fluorescent method showed 15.90×10–4 M for compound (1) and 8.95×10–5 M for compound (2), respectively. In addition, test paper-strips containing sensor 2 indicated noticeable results for 'naked eye' detection of cyanide in an aqueous medium.

Series of 2-aryl-4,5-diphenyl-1H-imidazole derivatives of 2-(4-hydroxy-3-methoxyphenyl)-4,5-diphenyl-1H-imidazole (1), 2-(4,5-dimethoxyphenyl)-4,5-diphenyl-1H-imidazole (2) and 2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazole (3) were produced and evaluated for their in vitro antimalarial activities against the chloroquine-sensitive Plasmodium falciparum 3D7 strain. A molecular docking study was also carried out against the crystal protein of Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) (PDB ID: 1J3I.pdb) to predict the interaction between the compounds and protein. The physicochemical and pharmacokinetic parameters were computationally performed to predict the parameters of the absorption, distribution, metabolism, excretion, and toxicity (ADMET). Imidazoles were synthesized from aryl aldehyde derivatives with benzyl and ammonium acetate in glacial acetic acid using microwave-assisted-organic synthesis. Compounds 1, 2, and 3 were produced in 64.33, 50.56, and 70.55% yields, respectively. The IC50 of compounds 1, 2, and 3 against chloroquine-sensitive Plasmodium falciparum 3D7 strain was found to be 1.14, 5.28, and 2.42 µM, respectively. The molecular docking study agreed with the in vitro data by showing the lowest CDOCKER energy for compound 1 (-47.48 kcal/mol), followed by 3 (-43.79 kcal/mol) and 2 (-41.47 kcal/mol). The physicochemical and pharmacokinetic parameters showed that imidazoles 1, 2, and 3 obeyed Lipinski rules of five to propose as lead compounds for the antimalarial agents.

Crude oil is an indispensable energy feedstock for daily activities, although some amounts of metallic porphyrins components with undesired characteristics have been identified. These constituents are assumed to originate from the geochemical process of chlorophyll and heme derivatives. In addition, their chemical structures have been thoroughly characterized using spectroscopy techniques, while several analytical methods were adopted in the detection and concentration quantification in the crude oils. The metallic porphyrins have several demerits, including the deactivation of used catalysts, contamination of the treated petrochemical products, and corrosion of the industrial equipment. Also, the removal process is considered challenging due to the strong interaction with the asphaltene fraction of crude oil. This review article, therefore, provides brief information on the origin, physicochemical properties, and possible removal technology of metallic porphyrins from crude oil samples. Besides, a better understanding of chemistry contributes a useful insight towards the development and establishment of better futuristic processing technology.

Erlotinib, Afatinib, and WZ4002 are quinazoline derivative compounds and classified as first, second, and third-generation EGFR inhibitor. All inhibitors have been given directly to cancer patients for many years but find some resistance. These three compounds are candidates as the lead compound in designing a new inhibitor. This work aims to design a new potential quinazoline derivative as an EGFR inhibitor focused on the molecular docking result of the lead compound. The research method was started in building a pharmacophore model of the lead compound then used to design a new potential inhibitor by employing the AutoDock 4.2 program. Molecular dynamics simulation evaluates the interaction of all complexes using the Amber15 program. There are three new potential compounds (A1, B1, and C1) whose hydrogen bond interaction in the main catalytic area (Met769 residue). The Molecular Mechanics Generalized Born Surface Area (MM-GBSA) binding energy calculation shows that B1 and C1 compounds have lower binding energies than erlotinib as a positive control, which indicates that B1 and C1 are potential as EGFR inhibitor.

This study describes simple synthetic method to prepare 1-(2-methoxybenzyl)-1,10-phenanthrolin-1-ium bromide from gandapura oil. The salt were synthesized in four steps. Initially, commercial gandapura oil was directly subjected to the alkylation reaction under basic condition using dimethyl sulfate to give methyl 2-methxybenzoate in 86% yield. Next, the produced benzoate ester was reduced by LiAlH4 to produce 2-methoxybenzyl alcohol in 67% yield. The treatment of benzyl alcohol with phosphorus tribromide under solvent free condition produced the corresponding benzyl bromide (in 67% yield), which was directly introduced into bimolecular nucleophilic substitution reaction with 1,10-phenantroline monohydrate to finally give the desired product in 63% yield.

Compound of 3,3'-(4-(2-amino-4,5-dimethoxyphenyl)pyridine-2,6-diyl)dianiline (CHP) has been synthesized via three-step synthetic procedure from veratraldehyde as starting material and 4-(4,5-dimethoxy-2-nitrophenyl)-2,6-bis(3-nitrophenyl)pyridine (CHP-1) as an intermediate compound. The CHP-1 was reduced using hydrazine hydrate catalyzed by 10% Pd/C to the final target of CHP. The spectroscopic study revealed that CHP in acetonitrile could detect formaldehyde through fluorescence enhancement and showed color change from yellow to blue under the 365 nm portable ultraviolet lamp as a response. Based on the fluorescence spectra, the emission wavelength of CHP in acetonitrile was shifted from 526 to 480 nm after addition of formaldehyde. Limit detection (LOD), selectivity, sensitivity, and computational study geometry of CHP as a chemosensor for formaldehyde has also been investigated. CHP could also be applied as a test paper for the detection of formaldehyde qualitatively.

Lung cancer was a second common cancer case due to the high cigarette smoking activity both in men and women. One of protein receptor which plays an important role in the growth of the tumor is Epidermal Growth Factor Receptor (EGFR). EGFR protein is the most frequent protein mutation in cancer and promising target to inhibit the cancer growth. In this work, the stability of the hydrogen bond as the main interaction in the inhibition mechanism of cancer will be evaluated using molecular dynamics simulation. There were two compounds (A1 and A2) as new potential inhibitors that were complexed against the EGFR protein. The dynamic properties of each complexed were compared with respect to erlotinib against EGFR. The result revealed that both compounds had an interaction in the main catalytic area of protein receptor which is at methionine residue. Inhibitor A1 showed additional interactions during simulation time but the interactions tend to be weak. Inhibitor A2 displayed a more stable interaction. Following dynamics simulation, binding free energy calculation was performed by two scoring techniques MM/GB(PB)SA method and gave a good correlation with the stability of the complex. Furthermore, potential inhibitor A2 had a lower binding free energy as a direct consequence of the stability of hydrogen bond interaction.

Objective: To investigate in vitro antimalarial activity of chalcone derivative compounds against Plasmodium falciparum 3D7 (Pf3D7) strain and in silico antimalarial activity. Methods: Synthesis of the chalcone derivatives was conducted via Claisen-Schmidt method using NaOH 60% base as catalyst. An in vitro antimalarial activity assay was carried out according to the Rieckmann method against the chloroquine-sensitive Pf3D7 strain. Molecular docking studies of the prepared compounds were performed using Discovery Studio 3.1 (Accelrys, Inc., San Diego, USA) software to dihydrofolate reductases–thymidylate synthase (PfDHFR-TS) protein with Protein Data Bank ID of 1J3I.pdb (sensitive-protein) and ID: 4DP3.pdb (resistance-protein). Results: This work has successfully synthesized seven chalcone derivatives with a great antimalarial activity. It has been revealed that allyloxy, hydroxy and alkoxy functional groups could increase the antimalarial activity of the chalcone derivatives. The best antimalarial activity of the prepared compounds was possessed by 3b with an IC50 value of 0.59 μM and categorized as an excellent antiplasmodial. Molecular docking studies of 3b showed binding interaction with the amino acid residues such as Ala16, Ile164, Phe58, Tyr170 of the 1J3I.pdb protein and also Ala16, Phe58, Ile112, Met55 of the 4DP3.pdb protein. Conclusions: An in vitro antimalarial assay of the prepared chalcone derivative (3a–g) showed an excellent and good antiplasmodial activity against the chloroquine-sensitive Pf3D7 strain. In silico antimalarial studies revealed that 3a–g made binding interaction with both sensitive-protein (1J3I.pdb) and resistance-protein (4DP3.pdb), which means that they were both active against chloroquine-sensitive and resistant plasmodium strain.

A novel styrene (1) and azo-styrene (2) based chemosensor from vanillin has been successfully synthesized. Sensor 1 was obtained by one step Knoevenagel condensation of Ultrasound method and sensor 2 by coupling diazo and Knoevenagel condensation reaction. Both of sensors showed high sensitivity and selectivity to detect CN- in aqueous media, even the presence of other anions, such as F-, Cl-, Br-, I-, CO32-, SO42-, H2PO4-, and AcO-. Colorimetric sensing of sensor 1 is inclined to be deprotonating of sensor binding site in the presence of cyanide and consequently improve the selectivity and sensitivity in sensing cyanide which displayed color change of sensor from yellowness to red-purple and then purple in 1 min. Sensor 2 exhibited chemodosimeter phenomenon which is caused by the nucleophilic addition of cyanide with a colour change from green to greenish-blue. The results enable to do an anion detection by a naked eye.

Telah dilakukan sintesis kemosensor anion senyawa 4-(2,6-difenil-piridin-4-il)-2-metoksi-fenol (DPMF). Sintesis senyawa target DPMF dilakukan melalui senyawa antara kalkon dengan rendemen reaksi 77%. Uji sebagai sensor anion dilakukan dalam pelarut DMSO-air terhadap anion F-, Cl-, Br-, CN- dan H2PO4-. Senyawa DPMF ini menghasilkan perubahan warna dari tidak berwarna menjadi kuning pada penambahan anion CN-. Analisis spektrofotometer UV-vis pada senyawa DPMF menghasilkan perubahan λmak = 320 nm ke λmak = 370 nm pada penambahan anion CN-. Limit deteksi terhadap anion CN- sebesar 4,11x10-6M. Senyawa ini juga dapat berperan sebagai kemosensor fluoresen dengan sistem “ON-OFF”.

The interactions between sensor chalcone of 3-(4-hydroxy-3-methoxyphenyl)-1-phenyl-2-propen-1-one (1) and anions (F–, Cl–, Br–, CN–, CO32–, and SO42–) have been experimentally and TD-DFT theoretically investigated. Sensor (1) showed a naked-eye detectable color change from yellow to red upon addition of F–, CO32–, CN–, and SO42– anions in DMSO, whereas no significant color change was observed upon addition of Cl– and Br– anions. The interaction models were predicted by optimizing (1)-anion complex using DFT/B3LYP method. Optimized (1)-anion complexes showed that sensor (1) was deprotonated by CO32–, CN–, F–, and SO42–. The formation of deprotonated sensor (1)– was responsible for the colorimetric signaling. Absorption spectra of neutral and deprotonated sensor were calculated using TD-DFT method. The calculated spectra were in good agreement with experimental results.

An SPE followed by HPLC-DAD method with ion pair chromatography technique to analyze pharmaceuticals with acethylcholinesterase activity including pyridostigmine (PYR), galathamine (GAL), neostigmine (NEO), eserine (ESE), and donepezil (DON) in water samples was developed. Acetylcholinesterase (AChE) inhibitors have been used to treat less severe dementias such as Alzheimer’s disease. Chromatographic separation was achieved using reversed-phase SymmetryShield column using gradient system with mobile phase consisting of H2O/ACN (99:1, v/v) as mobile phase A with 10 mM sodium 1-hexanesulfonate and 0.1% acetic acid (HAc). The HPLC/DAD method was linear between concentrations of 5 to 100 ng/μL. The IDL and IQL ranged from 0.50 to 1.25 ng/μL and 1.5 to 3.0 ng/μL, respectively. SPE was used to extract and clean up the target substances in spiked pure water, tap water, and wastewater samples. The application of extraction method of 5 target substances in wastewater sample was divided into 2 parts: Oasis WCX (6 mL, 500 mg) for PYR and Oasis HLB (6 mL, 200 mg) for GAL, NEO, ESE and DON. The developed SPE and HPLC/DAD method is applicable for quantification of the 5 target substances in water samples in a concentration range > 50 µg/L and assumable lower for DON (> 25 µg/L).

Microbial infections remains a serious challenge in food industries due to their resistance to some of the well-known antibacterial and antifungal agents. In this work, a novel monomyristoyl ester (fructosyl monomyristate) and two other derivatives (i.e., glucosyl and galactosyl monomyristates) were successfully synthesized from myristic acid and monosaccharides in two-step reactions. First, the myristic acid was converted to myristoyl chloride, and then the myristoyl chloride was reacted with fructose, glucose and galactose separately to produce the corresponding monosaccharide monomyristate derivatives. The structures of the synthesized products were confirmed by Fourier transform infrared (FTIR), proton and carbon nuclear magnetic resonance (1H- and 13C-NMR), and mass spectral (MS) data. The monomyristates esters were obtained in reaction yields of 45.80%−79.49%. The esters were then evaluated for their antimicrobial activity using the disc diffusion test. It was found that the esters exhibited a medium antibacterial activity against gram-positive bacteria; however, they showed a weak antibacterial activity against gram-negative bacteria. Amongst the esters, galactosyl myristate yielded the highest antibacterial activity against Salmonella typhimurium, Staphylococcus aureus and Bacillus subtilis, while glucosyl monomyristate exhibited the highest antibacterial activity only against Escherichia coli. Additionally, all products showed remarkable antifungal activity against Candida albicans. These findings demonstrate that monosaccharide monomyristate derivatives are promising for use as biocompatible antimicrobial agents in the future.

Preparations of azo, imine and azo-imine derivatives from vanillin as an indicator of acid-base titration have been carried out. The azo derivative of 4-hydroxy-3-methoxy-5-(phenylazo)benzaldehyde 2 was produced by diazotitation reaction of vanillin in 37.04% yield. The azo product was then refluxed with aniline in ethanol to yield azo-imine derivatives, 2-methoxy-6-(phenylazo)-4-((phenylimino)methyl)phenol 1 in 82.21% yield. The imine derivative, 2-methoxy-4-((phenylimino)methyl)-phenol 3 was obtained by refluxing of vanillin and aniline mixture in ethanol solvent and produced 82.17% yield. The imine product was then reacted with benzenediazonium chloride salt. However, the products indicated hydrolyzed product of 4-hydroxy-3-methoxy-5-(phenylazo)benzaldehyde 2 in 22.15% yield. The 2-methoxy-4-((phenylimino)methyl)phenol 2 could be used as an indicator for titration of NaOH by H2C2O4 with maximum concentration of H2C2O4 0.1 M while the target compound 1 could be used as titration indicator for titration of NaOH with H2C2O4 with same result using phenolphthalein indicator.

Synthesis and antioxidant activity of 2-methoxy-4,6-di(prop-1-enyl) phenol from eugenol have been investigated. Synthesis was conducted through three stages of reaction. The first step was CTAB micellar catalytic O-allylation reaction at room temperature, to give 4-allyl-1-(allyloxy)-2-methoxybenzene (2). Compound (2) was subsequently heated for Claisen rearrangement and produced 2,4-diallyl-6- methoxyphenol (3). The final steps was isomerization of compound (3) in alkaline conditions in ethylene glycol, to yield 2-methoxy-4,6-di(prop-1-enyl) phenol (4). Antioxidant activity test was conducted by TBARS and DPPH methods. TBARS test showed that the compound (4) at a concentration of 50 μM could inhibit the oxidation of linoleic acid shown by the increasing of time lag phase (96 ± 2.94 min), reducing the rate of propagation (± 54.54%) and reducing of malonal dialdehyde (MDA) formation (68.04 ± 0.84%). The DPPH test revealed that compound (4) indicated DPPH free radical scavenging activity with IC50 107.66 μM and comparable with IC50 for BHT 107.37 μM.

Quantitative Structure-Activity Relationship (QSAR) analysis of substituted flavone / flavonol compounds has been carried out by applying Hansch Analysis using their physicochemical properties as the predictors. The properties i.e. log P, (log P)2, core-core interaction energy (Eint), volume (V), molecular mass (M), dipole moment (μ), heat of formation ( ΔHof), binding energy (Ei), total energy (ET), surface area (L), polarizability (α), molar refractivity (RM), hidration energy (EH), electronic energy (Eel) and isolated atomic energy (Eat,is), were obtained on the basis of geometry optimization using PM3 semiempirical method. The QSAR analysis used antiradical activities (% A) as the dependent variable and has been done by applying multilinear regression technique. The result showed that QSAR equations i.e. % A = 77.426 - 67.343 [log P] + 3.160 [(log P)2 + 67.884 [α] + 6.63x10-4 [ Eint] - 5.280 [L] + 1.179 [V] + 0.447 [M] - 11.000 [μ] + 0.093 [Ei] + 3.433 [EH] - 3.44x10-3 [ET] (n = 16 ; r2 = 0.987 ; SD = 9.205; Fcal/Ftable = 4.797) Keywords: QSAR, antiradical, flavone, flavonol

The synthesis of azo compounds from eugenol has been carried out by diazotation reaction. The diazonium salt was produced by reaction of aniline and sodium nitrite in acid condition at 0-5 °C temperature to yield benzenediazonium chloride salt. The salt was then reacted with eugenol to produce the azo derivatives. The azo product was analyzed by IR, 1H-NMR, dan GC-MS spectrometer. The results showed that the reaction of benzenediazonium chloride with eugenol gave 4-allyl-2-methoxy-6-hydroxyazobenzene in 34.27% yield for 30 minutes reaction. The derivative of azo compound was dissolved in ethanol and then the color changing was observed in range of pH 9.8-11.1 from yellow to red. Application for titration indicator for acetic acid titrated with sodium hydroxide showed error less than 3.20% compared with phenol phtaline indicator. Keywords: Eugenol, Azo compound, titration indicator

The nucleophilic substitution reaction to quaternary Mannich base from vanillin has been investigated. Mannich reaction to vanillin was carried out by refluxing mixture of vanillin, formaldehyde and dimethyl amine. Quaternary ammonium halide salt was obtained from reaction of Mannich vanillin base with methyl iodide in THF solvents and yielded 93.28 %. Nucleophilic substituion to the halide salts with cyanide nucleophile produced 4-hidroxy-3-methoxy-5-(cyano)methylbenzaldehyde in 54.39% yield. Reaction with methoxyde ion yielded 4-hydroxy- 3-methoxy-5-(methoxy) -methylbenzaldehyde in 67.80% yield. The nucleophilic substitution reaction showed that trimethylamino substituent of quaternary Mannich base can act as a good leaving group on nucleophilic substitution reactions. Keywords: Mannich reaction, vanillin, nucleophilic substitution

Studies of the Lewis Acid (AlCl3 and BF3-methanol) to isoeugenol and isoeugenyl acetate have been conducted. Reactions were carried out by stirring of isoeugenol and isoeugenyl acetate for 4 days at room temperature.Structure analysis of the products using IR, MS, 1H NMR and 13C NMR spectrophotometer showed that cyclic dimer product has been obtained white crystal, 175 oC, as a 1-ethyl-5-hydroxy-3-(4-hydroxy-3-methyl phenyl)-6-methoxy-2-methyl indane. Keywords: csoeugenol, cyclic dimer, clove leaf oil, indane.

Structure Activity Relationship (SAR) technique between the theoretical parameters and antioxidant activities of isoeugenol, eugenol, vanillin and their derivatives as Mannich reaction products, have been analyzed. Antioxidant activities were examined by oxidation reaction of oleic acid at 60 °C with b-carotene methods, whereas theoretical parameters of the activities were determined by calculating Bonding Dissociation Enthalpy (BDE) and net charge of oxygen atom(-OH) using AM1 semi empiric methods. The result from both test showed in the following orders: BHT > Mannich product of isoeugenol > isoeugenol > Mannich product of eugenol > eugenol > Mannich product of vanillin > vanillin. The antioxidant activities increase with small the BDE value and high the net charge. Electron donating groups will increase the antioxidants activity with lowering the BDE value and increasing the net charge, while electron-withdrawing groups will decrease antioxidants activity. Keywords: SAR, antioxidants, Bonding Dissociation Entalphy, eugenol.