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Malcolm F. G. Stevens - One of the best experts on this subject based on the ideXlab platform.

  • antitumor Benzothiazoles 16 1 synthesis and pharmaceutical properties of antitumor 2 4 aminophenyl benzothiazole amino acid prodrugs
    Journal of Medicinal Chemistry, 2002
    Co-Authors: Ian Hutchinson, AD Westwell, Sharon Jennings, Rao B Vishnuvajjala, Malcolm F. G. Stevens
    Abstract:

    A series of water-soluble l-lysyl- and l-alanyl-amide prodrugs of the lipophilic antitumor 2-(4-aminophenyl)Benzothiazoles has been synthesized to address formulation and bioavailability issues related to the desired parenteral administration of the chosen clinical candidate. The prodrugs exhibit the required pharmaceutical properties of good water solubility (in weak acid) and stability at ambient temperature and degradation to free base in vivo. The lysyl-amide of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (NSC 710305, 6d) has been selected for phase 1 clinical evaluation.

  • Antitumor Benzothiazoles. 14. Synthesis and in vitro biological properties of fluorinated 2-(4-aminophenyl)Benzothiazoles.
    Journal of Medicinal Chemistry, 2001
    Co-Authors: Ian Hutchinson, AD Westwell, Mei-sze Chua, Helen L. Browne, Valentina Trapani, Tracey D. Bradshaw, Malcolm F. G. Stevens
    Abstract:

    Synthetic routes to a series of mono- and difluorinated 2-(4-amino-3-substituted-phenyl)Benzothiazoles have been devised. Whereas mixtures of regioisomeric 5- and 7-fluoro-Benzothiazoles were formed from the established Jacobsen cyclization of precursor 3-fluoro-thiobenzanilides, two modifications to this general process have allowed the synthesis of pure samples of these target compounds. Fluorinated 2-(4-aminophenyl)Benzothiazoles were potently cytotoxic (GI50 10 μM) against PC 3 prostate, nonmalignant HBL 100 breast, and HCT 116 colon cells. The biphasic dose−response relationship characteristically shown by the benzothiazole series against sensitive cell lines was exhibited by the 4- and 6-fluoro-Benzothiazoles (10b,d) but not by the 5- and 7-fluoro-Benzothiazoles (10h,i). The most potent broad spectrum agent in the NCI cell panel was 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (10h) which, un...

  • antitumor Benzothiazoles 8 synthesis metabolic formation and biological properties of the c and n oxidation products of antitumor 2 4 aminophenyl Benzothiazoles
    Journal of Medicinal Chemistry, 1999
    Co-Authors: Eiji Kashiyama, AD Westwell, Ian Hutchinson, Mei-sze Chua, Tracey D. Bradshaw, Sherman F Stinson, Lawrence R Phillips, Gurmeet Kaur, Edward A Sausville, Malcolm F. G. Stevens
    Abstract:

    2-(4-Aminophenyl)Benzothiazoles 1 and their N-acetylated forms have been converted to C- and N-hydroxylated derivatives to investigate the role of metabolic oxidation in the mode of action of this series of compounds. 2-(4-Amino-3-methylphenyl)benzothiazole (1a, DF 203, NSC 674495) is a novel and potent antitumor agent with selective growth inhibitory properties against human cancer cell lines. Very low IC50 values (<0.1 μM) were encountered in the most sensitive breast cancer cell lines, MCF-7 and T-47D, whereas renal cell line TK-10 was weakly inhibited by 1a. Cell lines from the same tissue origin, MDA-MB-435 (breast), CAKI-1 (renal), and A498 (renal), were insensitive to 1a. Accumulation and metabolism of 1a were observed in sensitive cell lines only, with the highest rate of metabolism occurring in the most sensitive MCF-7 and T-47D cells. Thus, differential uptake and metabolism of 1a by cancer cell lines may underlie its selective profile of anticancer activity. A major metabolite in these sensitiv...

  • 2 4 aminophenyl Benzothiazoles novel agents with selective profiles of in vitro anti tumour activity
    British Journal of Cancer, 1998
    Co-Authors: Tracey D. Bradshaw, Rj Schultz, Kd Paull, S Wrigley, D F Shi, Malcolm F. G. Stevens
    Abstract:

    2-(4-Aminophenyl)benzothiazole (CJM 126) elicits biphasic growth-inhibitory effects against a panel of oestrogen receptor-positive (ER+) and oestrogen receptor-negative (ER-) human mammary carcinoma cell lines in vitro, yielding IC50 values in the nM range. Substitutions adjacent to the amino group in the 2-phenyl ring with a halogen atom or methyl group enhance potency in sensitive breast lines (pM IC50 values). Transient biphasic dose responses were induced but rapidly eradicated after specific drug exposure periods. Two human prostate carcinoma cell lines were refractory to the growth-inhibitory properties of 2-(4-aminophenyl)Benzothiazoles; IC50 values > 30 microM were obtained. Potency and selectivity were confirmed when compounds were examined in the National Cancer Institute's Developmental Therapeutics screen; the spectrum of activity included specific ovarian, renal, colon as well as breast carcinoma cell lines. Moreover, comparing 6-day and 48-h incubations, the exposure time-dependent nature of the biphasic response was corroborated. Differential perturbation of cell cycle distribution followed treatment of MCF-7 and MDA 468 cells with substituted 2-(4-aminophenyl)Benzothiazoles. In MDA 468 populations only, accumulation of events in G2/M phase was observed. Two MCF-7 cell lines were established with acquired resistance to CJM 126 (IC50 values > 20 microM), which exhibit cross-resistance to substituted Benzothiazoles, but equal sensitivity to tamoxifen and doxorubicin. Compared with standard anti-tumour agents evaluated in the National Cancer Institute in vitro cell panel, Benzothiazoles revealed unique profiles of growth inhibition, suggesting a mode(s) of action shared with no known clinically active class of chemotherapeutic agents.

  • antitumor Benzothiazoles 3 1 synthesis of 2 4 aminophenyl Benzothiazoles and evaluation of their activities against breast cancer cell lines in vitro and in vivo
    Journal of Medicinal Chemistry, 1996
    Co-Authors: Dongfang Shi, Tracey D. Bradshaw, Samantha Wrigley, Carol Jane Mccall, Peter Lelieveld, Iduna Fichtner, Malcolm F. G. Stevens
    Abstract:

    A new series of 2-(4-aminophenyl)Benzothiazoles substituted in the phenyl ring and benzothiazole moiety has been synthesized by simple, high-yielding routes. The parent molecule 5a shows potent inhibitory activity in vitro in the nanomolar range against a panel of human breast cancer cell lines, but is inactive (IC50 > 30 μM) against other cell types:  activity against the sensitive breast lines MCF-7 and MDA 468 is characterized by a biphasic dose−response relationship. Structure−activity relationships derived using these cell types has revealed that activity follows the heterocyclic sequence benzothiazole > benzoxazole ≫ benzimidazole and that 2-(4-aminophenyl)Benzothiazoles bearing a 3‘-methyl- 9a, 3‘-bromo- 9c, 3‘- iodo- 9f, and 3‘-chloro-substituent 9i are especially potent and their activity extends to ovarian, lung, and renal cell lines. Four compounds have been evaluated in vivo against human mammary carcinoma models in nude mice. Compound 9a showed the most potent growth inhibition against the ER...

Thorsten Reemtsma - One of the best experts on this subject based on the ideXlab platform.

  • determination of benzotriazole corrosion inhibitors from aqueous environmental samples by liquid chromatography electrospray ionization tandem mass spectrometry
    Analytical Chemistry, 2005
    Co-Authors: Stefan Weiss, Thorsten Reemtsma
    Abstract:

    The first method for the determination of commonly used corrosion inhibitors in environmental water samples by liquid chromatography-electrospray ionization-tandem mass spectrometry is presented. Benzotriazole (BTri) and the two isomers of tolyltriazole (5- and 4-TTri) are separated in an isocratic run. By gradient elution, BTri, 4-TTri, 5-TTri, and xylyltriazole can be determined simultaneously with three Benzothiazoles, but here TTri isomers coelute. The instrumental detection limit of 2 pg allows the determination of the three most important benzotriazoles from municipal wastewater and most surface waters by direct injection into the HPLC system without previous enrichment. When solid-phase extraction is employed with mean recovery rates of 95-113%, the limit of quantification for benzotriazoles range from 10 ng/L in groundwater to 25 ng/L in untreated wastewater. BTri and TTri were determined in municipal wastewater in microgram per liter concentrations. Elimination in wastewater treatment appears to be poor, and BTri and TTri can be followed through a water cycle from treated municipal wastewater through surface water to bank filtrate used for drinking water production. The TTri isomers show markedly different biodegradation behavior with 4-TTri being more stable.

  • Occurrence, Sources, and Fate of Benzothiazoles in Municipal Wastewater Treatment Plants
    Environmental Science & Technology, 2005
    Co-Authors: Achim Kloepfer, Martin Jekel, Thorsten Reemtsma
    Abstract:

    A set of six Benzothiazoles was determined in effluents of three municipal wastewater treatment plants. Total concentrations of Benzothiazoles ranged from 1.9 to 6.7 μg/L, with benzothiazole-2-sulfonate (BTSA) being most prominent (35−70%), followed by benzothiazole, 2-hydroxybenzothiazole, and 2-methylthiobenzothiazole (MTBT). The removal of Benzothiazoles in tertiary municipal wastewater treatment was investigated in more detail in one of the plants during two sampling periods of several weeks. Total benzothiazole concentration decreased by 5−28% only. This very limited removal was primarily due to BTSA and MTBT that were either hardly removed or even increased in concentration. In street runoff Benzothiazoles exceeded the wastewater concentrations by 1 order of magnitude, showing that surface runoff can be a significant source of benzothiazole emission. In household wastewater total concentrations were in the range of 50−80% of that found in municipal wastewater. These investigations outline that benzo...

  • Occurrence of Benzothiazoles in municipal wastewater and their fate in biological treatment.
    Water Science and Technology, 2004
    Co-Authors: Achim Kloepfer, Martin Jekel, Regina Gnirss, Thorsten Reemtsma
    Abstract:

    A number of 2-substituted Benzothiazoles that are known to be used as fungicides, corrosion inhibitors and vulcanization accelerators in industry have been analyzed in municipal wastewater and the effluents of activated sludge and membrane bioreactor (MBR) treatment over a three month period. All six analytes were regularly detected in the municipal wastewater by liquid chromatography-mass spectrometry and amount to a total concentration of 3.4 μg/L. Of these compounds benzothiazole-2-sulfonic acid (1,700 ng/L), benzothiazole (850 ng/L) and 2-hydroxybenzothiazole (500 ng/L) were most prominent. The source of the benzothiazole emission is yet unknown. Activated sludge treatment did not reduce total benzothiazole concentration significantly. Removals of the individual compounds ranged from 90% for 2-mercaptobenzothiazole and 70% for hydroxybenzothiazole to 40% for benzothiazole. The concentration of benzothiazole-2-sulfonic acid increased by 20%, whereas 2-methylthiobenzothiazole increased by 160% during activated sludge treatment, likely due to the methylation of mercaptobenzothiazole. Total benzothiazole removal in two parallely operated MBRs was significantly better (43%) than in the conventional activated sludge treatment. Namely benzothiazole and benzothiazole-2-sulfonic acid were more effectively removed. This first systematic study on the occurrence of Benzothiazoles in municipal wastewater has shown that this is a relevant class of trace contaminants in municipal wastewater which is only incompletely removed in biological wastewater treatment. Emission from sewage treatment is dominated by the most polar benzothiazole-2-sulfonic acid. MBR treatment may reduce but cannot avoid this emission.

  • Extraction and analysis of various Benzothiazoles from industrial wastewater
    Analytica Chimica Acta, 1994
    Co-Authors: Oliver Fiehn, Thorsten Reemtsma, Martin Jekel
    Abstract:

    A method was developed for the analysis of benzothiazole, 2-mercaptobenzothiazole, 2_(methylthio)benzothiazole and 2-(thiocyanomethylthio)benzothiazole from industrial wastewater. It includes liquid-liquid extraction with ethyl acetate and toluene at pH 8.5, followed by liquid chromatographic (LC) analysis using a RP-18 column and an acetonitrile-water gradient with W detection at variable wavelengths. LC analysis is compared with the potential of gas chromatography and its advantages are discussed. Solid-phase extraction appeared not to be suitable for all compounds. The method allows the determination of benzothiazole derivatives without further clean-up down to contents of about 5 pg I-‘, with recovery rates exceeding 90% for all compounds. Dissolved organic carbon contents of up to 900 mg 1-l did neither interfere with extraction nor with chromatographic separation. Keywordr: Liquid chromatography; Extraction; Benzothiazoles; Wastewater; Waters 1. IJltroduction

Kurunthachalam Kannan - One of the best experts on this subject based on the ideXlab platform.

  • benzotriazoles and Benzothiazoles in human urine from several countries a perspective on occurrence biotransformation and human exposure
    Environment International, 2013
    Co-Authors: Alexandros G. Asimakopoulos, Nikolaos S. Thomaidis, Lei Wang, Kurunthachalam Kannan
    Abstract:

    Benzotriazole (BTR) and benzothiazole (BTH) derivatives are high-production-volume chemicals that are mainly used as corrosion inhibitors, and are widely distributed in the environment. BTR derivatives are found in plastics, dishwasher detergents, dry cleaning equipment, and de-icing/anti-icing fluids. BTH derivatives are found in rubber materials, herbicides, slimicides, algicides, fungicides, photosensitizers, azo dyes, drugs, de-icing/anti-icing fluids, and food flavors. However, exposure of humans to BTRs and BTHs is still not known. In this study, six BTRs (1H-benzotriazole, 1-hydroxy-benzotriazole, 4- and 5-hydroxy-benzotriazole [mixture of two isomers], tolyltriazole, xylyltriazole [or 5,6-dimethyl-1H-benzotriazole], and 5-chloro-benzotriazole) and six BTHs (benzothiazole, 2-morpholin-4-yl-benzothiazole, 2-hydroxy-benzothiazole, 2-methylthio-benzothiazole, 2-amino-benzothiazole, and 2-thiocyanomethylthio-benzothiazole) were determined in human urine collected from general populations in seven countries (the U.S., Greece, Vietnam, Korea, Japan, China, and India). The median urinary concentration of the sum of five BTRs (Σ5BTRs; 4- and 5-hydroxy-benzotriazole were not included) ranged from 0.2 (Korea) to 2.8 (India) ng/mL among the countries studied, with the highest concentration of 24.5 ng/mL found in a sample from China. Xylyltriazole was found more frequently in urine from all five Asian countries than in urine from the U.S. and Greece. The median concentration of the sum of the six BTHs (Σ6BTHs) ranged from 3.6 (U.S.) to 10.9 (Japan) ng/mL among the countries studied, with a maximum detection rate of 100% in urine samples from Vietnam; BTH was the predominant derivative, accounting for, on average, 43% of the Σ6BTH concentration. Based on the concentrations and detection rates of several BTR and BTH derivatives in urine, possible metabolic transformation pathways of these compounds were presented and human exposure doses calculated. The estimated daily intake doses of BTRs and BTHs were on the order of a few to few tens of micrograms per day.

  • Occurrence and removal efficiencies of benzotriazoles and Benzothiazoles in a wastewater treatment plant in Greece
    Science of The Total Environment, 2013
    Co-Authors: Alexandros G. Asimakopoulos, Kurunthachalam Kannan, Akinranti S. Ajibola, Nikolaos S. Thomaidis
    Abstract:

    Abstract Despite the widespread use of benzotriazoles and Benzothiazoles and the occurrence of these compounds in wastewater treatment plants (WWTPs), no earlier study has comprehensively examined their fate in WWTPs. In this study, an integrated liquid chromatography–tandem mass spectrometry (LC–ESI(+)MS/MS) method was developed and validated for simultaneous determination of four benzotriazoles and four Benzothiazoles in dissolved and particulate phases of wastewater (raw and treated), and in dewatered sewage sludge. The target benzotriazoles (BTRs) were 1H-benzotriazole, 1-hydroxy-benzotriazole, tolyltriazole, and xylyltriazole (or 5,6-dimethyl-1H-benzotriazole), and the target Benzothiazoles (BTHs) were benzothiazole, 2-hydroxy-benzothiazole, 2-methylthio-benzothiazole, and 2-amino-benzothiazole. The limits of detection ranged from 0.08 (2-methylthio-benzothiazole) to 17 ng/L (benzothiazole) for dissolved phase samples, and from 0.04 (2-methylthio-benzothiazole) to 13 ng/g dry weight (dw) (benzothiazole) for particular matter and sludge samples. The method was applied in the analysis of wastewater and sludge samples from the WWTP in Athens, Greece. All target chemicals were detected in wastewater samples, and in some cases the concentrations were significant, on the order of a few μg/L. In sludge samples, benzothiazole and tolyltriazole were present at the highest concentrations (174 and 116 ng/g dw, respectively). For benzotriazole and tolyltriazole, the removal efficiency was below 68%, and for Benzothiazoles, the removal efficiency was greater than 64% in the activated sludge treatment process. Both BTRs and BTHs showed low solid–liquid distribution coefficients.

  • Determination of Benzotriazoles and Benzothiazoles in Human Urine by Liquid Chromatography-Tandem Mass Spectrometry
    Analytical Chemistry, 2012
    Co-Authors: Alexandros G. Asimakopoulos, Anna A. Bletsou, Nikolaos S. Thomaidis, Kurunthachalam Kannan
    Abstract:

    Benzotriazole (BTR) and benzothiazole (BTH) derivatives are used in a wide variety of industrial and consumer products and have been reported to occur in the environment. Owing to a lack of analytical methods, human exposure to BTR and BTH is still unknown. In this study, a liquid chromatography-electrospray ionization tandem mass spectrometry (LC–ESI(+)MS/MS) method was developed for simultaneous determination of five 1,2,3-benzotriazoles and five 1,3-Benzothiazoles in human urine. The target benzotriazoles were 1H-benzotriazole, 1-hydroxy-benzotriazole, tolyltriazole, xylyltriazole (or 5,6-dimethyl-1H-benzotriazole), and 5-chloro-benzotriazole, and the target Benzothiazoles were benzothiazole, 2-hydroxy-benzothiazole, 2-methylthio-benzothiazole, 2-amino-benzothiazole, and 2-thiocyanomethylthio-benzothiazole. Urine specimens were enzymatically deconjugated with β-glucuronidase and extracted by a solid-phase extraction (SPE) procedure for the measurement of total concentrations (i.e., free + conjugated fo...

Alexandros G. Asimakopoulos - One of the best experts on this subject based on the ideXlab platform.

  • benzotriazoles and Benzothiazoles in human urine from several countries a perspective on occurrence biotransformation and human exposure
    Environment International, 2013
    Co-Authors: Alexandros G. Asimakopoulos, Nikolaos S. Thomaidis, Lei Wang, Kurunthachalam Kannan
    Abstract:

    Benzotriazole (BTR) and benzothiazole (BTH) derivatives are high-production-volume chemicals that are mainly used as corrosion inhibitors, and are widely distributed in the environment. BTR derivatives are found in plastics, dishwasher detergents, dry cleaning equipment, and de-icing/anti-icing fluids. BTH derivatives are found in rubber materials, herbicides, slimicides, algicides, fungicides, photosensitizers, azo dyes, drugs, de-icing/anti-icing fluids, and food flavors. However, exposure of humans to BTRs and BTHs is still not known. In this study, six BTRs (1H-benzotriazole, 1-hydroxy-benzotriazole, 4- and 5-hydroxy-benzotriazole [mixture of two isomers], tolyltriazole, xylyltriazole [or 5,6-dimethyl-1H-benzotriazole], and 5-chloro-benzotriazole) and six BTHs (benzothiazole, 2-morpholin-4-yl-benzothiazole, 2-hydroxy-benzothiazole, 2-methylthio-benzothiazole, 2-amino-benzothiazole, and 2-thiocyanomethylthio-benzothiazole) were determined in human urine collected from general populations in seven countries (the U.S., Greece, Vietnam, Korea, Japan, China, and India). The median urinary concentration of the sum of five BTRs (Σ5BTRs; 4- and 5-hydroxy-benzotriazole were not included) ranged from 0.2 (Korea) to 2.8 (India) ng/mL among the countries studied, with the highest concentration of 24.5 ng/mL found in a sample from China. Xylyltriazole was found more frequently in urine from all five Asian countries than in urine from the U.S. and Greece. The median concentration of the sum of the six BTHs (Σ6BTHs) ranged from 3.6 (U.S.) to 10.9 (Japan) ng/mL among the countries studied, with a maximum detection rate of 100% in urine samples from Vietnam; BTH was the predominant derivative, accounting for, on average, 43% of the Σ6BTH concentration. Based on the concentrations and detection rates of several BTR and BTH derivatives in urine, possible metabolic transformation pathways of these compounds were presented and human exposure doses calculated. The estimated daily intake doses of BTRs and BTHs were on the order of a few to few tens of micrograms per day.

  • Occurrence and removal efficiencies of benzotriazoles and Benzothiazoles in a wastewater treatment plant in Greece
    Science of The Total Environment, 2013
    Co-Authors: Alexandros G. Asimakopoulos, Kurunthachalam Kannan, Akinranti S. Ajibola, Nikolaos S. Thomaidis
    Abstract:

    Abstract Despite the widespread use of benzotriazoles and Benzothiazoles and the occurrence of these compounds in wastewater treatment plants (WWTPs), no earlier study has comprehensively examined their fate in WWTPs. In this study, an integrated liquid chromatography–tandem mass spectrometry (LC–ESI(+)MS/MS) method was developed and validated for simultaneous determination of four benzotriazoles and four Benzothiazoles in dissolved and particulate phases of wastewater (raw and treated), and in dewatered sewage sludge. The target benzotriazoles (BTRs) were 1H-benzotriazole, 1-hydroxy-benzotriazole, tolyltriazole, and xylyltriazole (or 5,6-dimethyl-1H-benzotriazole), and the target Benzothiazoles (BTHs) were benzothiazole, 2-hydroxy-benzothiazole, 2-methylthio-benzothiazole, and 2-amino-benzothiazole. The limits of detection ranged from 0.08 (2-methylthio-benzothiazole) to 17 ng/L (benzothiazole) for dissolved phase samples, and from 0.04 (2-methylthio-benzothiazole) to 13 ng/g dry weight (dw) (benzothiazole) for particular matter and sludge samples. The method was applied in the analysis of wastewater and sludge samples from the WWTP in Athens, Greece. All target chemicals were detected in wastewater samples, and in some cases the concentrations were significant, on the order of a few μg/L. In sludge samples, benzothiazole and tolyltriazole were present at the highest concentrations (174 and 116 ng/g dw, respectively). For benzotriazole and tolyltriazole, the removal efficiency was below 68%, and for Benzothiazoles, the removal efficiency was greater than 64% in the activated sludge treatment process. Both BTRs and BTHs showed low solid–liquid distribution coefficients.

  • Determination of Benzotriazoles and Benzothiazoles in Human Urine by Liquid Chromatography-Tandem Mass Spectrometry
    Analytical Chemistry, 2012
    Co-Authors: Alexandros G. Asimakopoulos, Anna A. Bletsou, Nikolaos S. Thomaidis, Kurunthachalam Kannan
    Abstract:

    Benzotriazole (BTR) and benzothiazole (BTH) derivatives are used in a wide variety of industrial and consumer products and have been reported to occur in the environment. Owing to a lack of analytical methods, human exposure to BTR and BTH is still unknown. In this study, a liquid chromatography-electrospray ionization tandem mass spectrometry (LC–ESI(+)MS/MS) method was developed for simultaneous determination of five 1,2,3-benzotriazoles and five 1,3-Benzothiazoles in human urine. The target benzotriazoles were 1H-benzotriazole, 1-hydroxy-benzotriazole, tolyltriazole, xylyltriazole (or 5,6-dimethyl-1H-benzotriazole), and 5-chloro-benzotriazole, and the target Benzothiazoles were benzothiazole, 2-hydroxy-benzothiazole, 2-methylthio-benzothiazole, 2-amino-benzothiazole, and 2-thiocyanomethylthio-benzothiazole. Urine specimens were enzymatically deconjugated with β-glucuronidase and extracted by a solid-phase extraction (SPE) procedure for the measurement of total concentrations (i.e., free + conjugated fo...

Yan Yin - One of the best experts on this subject based on the ideXlab platform.

  • a metal free and recyclable synthesis of Benzothiazoles using thiourea as a sulfur surrogate
    Tetrahedron Letters, 2015
    Co-Authors: Yan Yin, Hong Zhou, Xichen Liu, Haiying Chen, Heng Zhang, Ruiheng Tao, Fengkai Cheng, Yangbo Feng
    Abstract:

    Abstract Using odorless thiourea as the S source, Benzothiazoles and asymmetric disulfides could be obtained from thioformanilides through the tandem cyclization/nucleophilic addition/hydrolysis/nucleophilic substitution reaction. Furthermore, the obtained asymmetric disulfides could readily transfer to Benzothiazoles after nitro-reduction and amide formation reaction. This metal-free and recyclable synthetic methodology offered a time-efficient, less expensive, and environmentally friendly alternative to multifunctional Benzothiazoles.