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Due to its application as an anti-cancer drug, pazopanib (1) has attracted the interest of many researchers, and several studies on pazopanib synthesis have been reported over the years. This paper provides a novel route for synthesizing N,2,3-trimethyl-2H-indazol-6-amine (5), which is a crucial building block in the synthesis of pazopanib from 3-methyl-6-nitro-1H-indazole (6). By alternating between the reduction and two methylation steps, compound 5 was obtained in a yield comparable (55%) to what has been reported (54%). It is noteworthy that the last step of N2-methylation also yielded N,N,2,3-tetramethyl-2H-indazol-6-amine (5′) as a novel compound. Furthermore, the data presented in this paper can serve as a valuable resource for future research aimed at further refining the process of synthesizing pazopanib and its derivatives.

Efforts to improve the solar power conversion efficiencies of binary bulk heterojunction-type organic photovoltaic devices using an active layer consisting of a poly-(3-alkylthiophene) (P3AT) homopolymer and a suitable fullerene derivative face barriers caused by the intrinsic properties of homopolymers. To overcome such barriers, researchers might be able to chemically tailor homopolymers by means of monomer ratio-balanced block copolymerization to obtain preferable properties. Triblock copolymers consisting of three components—3-hexylthiophene (HT), 3-butylthiophene (BT), and 3-octylthiophene (OT)—were synthesized via Grignard metathesis (GRIM) polymerization. The component ratios of the synthesized block copolymers were virtually the same as the feeding ratios of the monomers, a fact which was verified using 1H-NMR spectra. All the copolymers exhibited comparable crystalline and melting temperatures, which increased when one type of monomer became dominant. In addition, their power conversion efficiencies and photoluminescence properties were governed by the major components of the copolymers. Interestingly, the HT component-dominated block copolymer indicated the highest power conversion efficiency, comparable to that of its homopolymer, although its molecular weight was significantly shorter.

The title compound, propyl gallate (III), is an important substance popularly used in the food, cosmetic and pharmaceutical industries. Current chemical syntheses of this compound are based on the acylation supported by thionyl chloride, DIC/DMAP or Fischer esterification using a range of homogenous and heterogenous catalysts. In this paper, an efficient, green, straightforward, and economical method for synthesizing propyl gallate using potassium hydrogen sulfate, KHSO4, as the heterogenous acidic catalyst has been developed for the first time. In addition, this paper provides a comprehensive spectral dataset for the title compound, especially the new data on DEPT and 2D NMR (HSQC and HMBC) spectra which are not currently available in the literature.

Sulfones are important building blocks in the construction of biologically active molecules or functional materials. The sulfonyl functional group in sulfones is so versatile that it can act as either a nucleophile, an electrophile, or a radical in different organic reactions. Recently, quinazoline sulfones have been used to build asymmetrical ether derivatives as inhibitors of signaling pathways governed by tyrosine kinases and the epidermal growth factor-receptor. In this paper, we report a facile synthesis of a novel quinazoline sulfone, 6-nitro-7-tosylquinazolin-4(3H)-one (III), using the modified protocol from 7-chloro-6-nitroquinazolin-4(3H)-one (I) and sodium p-toluenesulfinate (II). The structure of the title compound III was determined using mass-spectrometry, FT-IR, 1H-NMR, 13C-NMR, DEPT, HSQC (Heteronuclear single quantum coherence), HMBC (Heteronuclear Multiple Bond Correlation Spectroscopy) spectroscopies, and PXRD analysis.

Afatinib is a 4-anilinoquinazoline tyrosine kinase inhibitor (TKI) in the form of a dimaleate salt which is indicated for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). The most scalable route for the synthesis of this drug was reported in two Boehringer Ingelheim patents, in which the title compound, 4,7-dichloro-6-nitroquinazoline (IV), is an important intermediate. Compound IV is also present in a number of synthetic pathways for various 4,7-disubstituted quinazoline derivatives displaying high therapeutic potential. However, no detailed characterization of this popular compound has been reported, possibly due to its high instability. In this paper, IV was prepared in an overall yield of 56.1% by a 3-step process (condensation, nitration, and chlorination) from 2-amino-4-chlorobenzoic acid (I). The target compound has been for the first time fully characterized by melting point, mass-spectrometry, FT-IR, 1H-NMR and 13C-NMR spectroscopies.

Differentiation-inducing factor-1 [1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one (DIF-1)] is an important regulator of cell differentiation and chemotaxis in the development of the cellular slime mold Dictyostelium discoideum. However, the entire signaling pathways downstream of DIF-1 remain to be elucidated. To characterize DIF-1 and its potential receptor(s), we synthesized two fluorescent derivatives of DIF-1, boron-dipyrromethene (BODIPY)-conjugated DIF-1 (DIF-1-BODIPY) and nitrobenzoxadiazole (NBD)-conjugated DIF-1 (DIF-1-NBD), and investigated their biological activities and cellular localization. DIF-1-BODIPY (5 µM) and DIF-1 (2 nM) induced stalk cell differentiation in the DIF-deficient strain HM44 in the presence of cyclic adenosine monosphosphate (cAMP), whereas DIF-1-NBD (5 µM) hardly induced stalk cell differentiation under the same conditions. Microscopic analyses revealed that the biologically active derivative, DIF-1-BODIPY, was incorporated by stalk cells at late stages of differentiation and was localized to mitochondria. The mitochondrial uncouplers carbonyl cyanide m-chlorophenylhydrazone (CCCP), at 25–50 nM, and dinitrophenol (DNP), at 2.5–5 µM, induced partial stalk cell differentiation in HM44 in the presence of cAMP. DIF-1-BODIPY (1–2 µM) and DIF-1 (10 nM), as well as CCCP and DNP, suppressed chemotaxis in the wild-type strain Ax2 in shallow cAMP gradients. These results suggest that DIF-1-BODIPY and DIF-1 induce stalk cell differentiation and modulate chemotaxis, at least in part, by disturbing mitochondrial activity.

Yellow phosphorus is used widely in the world for production of phosphoric acid, various phosphates, flame retardant, detergent, water treatment, metal surface treatment, etc. After the production of yellow phosphorus, a large amount of phosphorus sludge is discharged to environment, causing environment pollution. This work focused on treatment of yellow phosphorus slag (YPS) and application of it as an absorbent for chromium (VI) ion and methylene blue. The YPS was first washed with water to remove phosphoferrite (FeP) and impurities and then being milled and transferred to a float sorting system to obtain YPS particles. The characteristics of YPS particles were determined by inductively coupled plasma-mass-spectrometry (ICP-MS), energy-dispersive X-ray spectroscopy (EDX), infrared spectroscopy (IR), scanning electron microscopy (SEM), X-ray diffraction (XRD), zeta potential, and nitrogen adsorption methods. The YPS particles were retreated with NaOH, HNO3, and EDTA solutions to evaluate the influence of these agents on metal ion and organic compound adsorption ability by YPS. The adsorption parameters of chromium (VI) ion and methylene blue (MB) by treated YPS particles were recognized by the ultraviolet-visible (UV-Vis) spectrometer. The effects of temperature, pH solution, and initial concentration of absorbed substances on the adsorption ability were investigated. The adsorption isotherms and adsorption kinetics of chromium (VI) ion and MB by YPS particles were also determined. The obtained results confirmed that the green technology used to treat the YPS2 particles is suitable to obtain an effective absorbent. The adsorption efficiency of YPS2 particles for removal of chromium (VI) ions is smaller than that for removal of MB in aqueous solutions. The adsorption isotherm of MB adsorption process is complied with the Langmuir isotherm while the adsorption kinetic fits well with the pseudo-second-order reaction model. The thermodynamic parameters of MB adsorption processed on YPS2 were calculated and discussed.

In this paper, the chromium, Cr (VI), ion adsorption ability of oyster shell samples collected from two sea regions in Vietnam (Phu Yen province and Quang Ninh province) was investigated and compared. The oyster shell samples were calcined at different temperatures and denatured by using ethylenediaminetetraacetic acid (EDTA). The Cr (VI) ion adsorption ability of the prismatic (PP) and nacreous (NP) shell layers of oysters was also evaluated. The characteristics of oyster shell samples before and after treatment were determined by using analysis methods including XRD, IR, BET, UV-Vis, and FESEM. The Langmuir, Freundlich, Temkin, and Dubinin–Radushkevich models and fit statistic equations were used to study the adsorption isotherms of Cr (VI) ion adsorption by oyster shells. The Cr (VI) ions adsorption kinetic has been set up using four reaction models consisting of first-order, pseudo-first-order, second-order, and pseudo-second-order reaction models. Effects of experimental factors on the Cr (VI) ion adsorption process using oyster shells were also investigated and discussed in this work.

Objectives: Sickness absenteeism has been rising in Singapore with sickness certification commonly performed by primary care physicians. The Primary Care Survey 2014 reported increased primary care demand driven by a rapidly ageing population and the prevalence of chronic disease. This article aims to determine the magnitude of outpatient sickness certification in all the polyclinics in Singapore and identify the demographic characteristics and factors influencing the taking of sick leave by the local multi-ethnic Asian patients. Design: A one-week, cross-sectional survey using computer-assisted interviews with age-stratified, systematically sampled patients was conducted at all 18 polyclinics in 2014. Sick leave data was then extracted from each polyclinic’s administrative system. Data was analysed with logistic regression to determine statistically significant factors. Results: The sickness certification rate was 22.6% during the study period with a weighted average duration of 1.42 days. Sickness certification was most associated with the younger age group (17–20 years; adjusted odd ratio (AOR) = 9.51), an acute condition (AOR = 24.8) and those living in 1–2 room public housing (AOR = 4.72). Among employees, those working in manufacturing industries had the most association with sickness certification while the finance and insurance industry had the least. An acute upper respiratory tract infection was the most frequent diagnosis for those who obtained medical certificates (38.7%). Conclusion: A medical certificate was issued in almost one-quarter of consultations in Singapore polyclinics. Sickness certification was predominated by short-term absence for acute conditions. Characterisation of sickness absenteeism among employees serves as a benchmark for future studies. Mitigation measures were discussed while exclusion of private primary care clinics probably led to an underestimation of the magnitude of sickness certification.

Cutting forces play very important in designing the tool machine, cutting tool, and in optimization of machining processes. Modeling and prediction of cutting forces by theoretical methods are quite difficult, so, this study was focused on modeling the cutting force in face milling process using combination of theoretical and experimental methods. This study was performed to model the milling forces (MFs) and determine the milling force coefficients (MFCs) in the face milling process of aluminum alloy Al7075 using square inserts. From theoretical and experimental methods, the relationship of average milling forces (AMFs) and feed per flute (ft) were determined as the linear regression. Using experimental data, the linear regressions of AMFs and feed per flute were determined with high values of determination coefficients (larger than 95 %). MFCs were determined including shear and edge MFCs (tangential shear MFC (Ktc) of 538.127 N/mm2, radial shear MFC (Krc) of 185.967 N/mm2, axial shear MFC (Kac) of -691.297 N/mm², tangential edge MFC (Kte) of 11.253 N/mm, radial edge MFC (Kre) of 6.991 N/mm, and axial edge MFC (Kae) of -32.971 N/mm. The MF models were successfully verified by comparing the measured and predicted MFs in face milling process of Al7075. The tendency and shape of predicted MFs were quite close to the measured ones. The differences between the predicted and the measured MFs can be due to the several reasons such as the influence of vibrations, the influence of cutting heat, etc., and these are also the limitations of this study. The modeling and prediction methods of this study can be used to model and predict the cutting forces in face milling of other milling types and other pairs of cutting tool and workpiece material as well. [ABSTRACT FROM AUTHOR]

This work focuses on optimizing process parameters in turning AISI 4340 alloy steel. A hybridization of Machine Learning (ML) algorithms and a Non-Dominated Sorting Genetic Algorithm (NSGA-II) is applied to find the Pareto solution. The objective functions are a simultaneous minimum of average surface roughness (Ra) and cutting force under the cutting parameter constraints of cutting speed, feed rate, depth of cut, and tool nose radius in a range of 50-375 m/min, 0.02-0.25 mm/rev, 0.1-1.5 mm, and 0.4-0.8 mm, respectively. The present study uses five ML models - namely SVR, CAT, RFR, GBR, and ANN - to predict Ra and cutting force. Results indicate that ANN offers the best predictive performance in respect of all accuracy metrics: root-mean-squared-error (RMSE), mean-absolute-error (MAE), and coefficient of determination (R2). In addition, a hybridization of NSGAII and ANN is implemented to find the optimal solutions for machining parameters, which lie on the Pareto front. The results of this multi-objective optimization indicate that Ra lies in a range between 1.032 and 1.048 μm, and cutting force was found to range between 7.981 and 8.277 kgf for the five selected Pareto solutions. In the set of non-dominated keys, none of the individual solutions is superior to any of the others, so it is the manufacturer's decision which dataset to select. Results summarize the value range in the Pareto solutions generated by NSGAII: cutting speeds between 72.92 and 75.11 m/min, a feed rate of 0.02 mm/rev, a depth of cut between 0.62 and 0.79 mm, and a tool nose radius of 0.4 mm, are recommended. Following that, experimental validations were finally conducted to verify the optimization procedure. [ABSTRACT FROM AUTHOR]