- COMPOUNDS WITH COPPER- OR ZINC-ACTIVATED TOXICITY AGAINST MICROBIAL INFECTION
-
Heterocyclic compounds with a novel pyrazole thioamide-based NNSN structural motif, having highly effective zinc- or copper-activated toxicity against microbial infections at micromolar or nanomolar minimum inhibitory concentrations (MIC), and methods of making and using same.
- -
-
-
- A more sustainable isothiocyanate synthesis by amine catalyzed sulfurization of isocyanides with elemental sulfur
-
Isothiocyanates (ITCs) are typically prepared using amines and highly toxic reagents such as thiophosgene, its derivatives, or CS2. In this work, an investigation of a multicomponent reaction (MCR) using isocyanides, elemental sulfur and amines revealed that isocyanides can be converted to isothiocyanates using sulfur and catalytic amounts of amine bases, especially DBU (down to 2 mol%). This new catalytic reaction was optimized in terms of sustainability, especially considering benign solvents such as Cyrene or γ-butyrolactone (GBL) under moderate heating (40 °C). Purification by column chromatography was further optimized to generate less waste by maintaining high purity of the product. Thus, E-factors as low as 0.989 were achieved and the versatility of this straightforward procedure was shown by converting 20 different isocyanides under catalytic conditions, while obtaining moderate to high yields (34-95%). This journal is
- Nickisch,Conen,Gabrielsen,Meier
-
p. 3134 - 3142
(2021/01/28)
-
- Synthesis of isothiocyanates using DMT/NMM/TsO? as a new desulfurization reagent
-
Thirty-three alkyl and aryl isothiocyanates, as well as isothiocyanate derivatives from esters of coded amino acids and from esters of unnatural amino acids (6-aminocaproic, 4-(aminomethyl)benzoic, and tranexamic acids), were synthesized with satisfactory or very good yields (25–97%). Synthesis was performed in a “one-pot”, two-step procedure, in the presence of organic base (Et3 N, DBU or NMM), and carbon disulfide via dithiocarbamates, with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TsO? ) as a desulfurization reagent. For the synthesis of aliphatic and aromatic isothiocyanates, reactions were carried out in a microwave reactor, and selected alkyl isothiocyanates were also synthesized in aqueous medium with high yields (72–96%). Isothiocyanate derivatives of L-and D-amino acid methyl esters were synthesized, under conditions without microwave radiation assistance, with low racemization (er 99 > 1), and their absolute configuration was confirmed by circular dichroism. Isothiocyanate derivatives of natural and unnatural amino acids were evaluated for antibacterial activity on E. coli and S. aureus bacterial strains, where the most active was ITC 9e.
- Janczewski, ?ukasz,Kolesińska, Beata,Kr?giel, Dorota
-
-
- 4-Dimethylaminopyridine-catalyzed synthesis of isothiocyanates from amines and carbon disulfide
-
Isothiocyanates were synthesized by reactions between primary amines and CS2 in the presence of 4-dimethylaminopyridine as a catalyst and tert-butyl hydroperoxide as an oxidant. Various aryl, benzyl, alkyl, and hydroxyl amines were transformed into the corresponding isothiocyanates in 41–82% yields.
- Rong, Hao-Jie,Chen, Tao,Xu, Ze-Gang,Su, Tian-Duo,Shang, Yu,Wang, Yong-Qiang,Yang, Cui-Feng
-
-
- Synthesis and antitumor activity of novel pyridazinone derivatives containing 1,3,4-thiadiazole moiety
-
A series of novel pyridazinone derivatives containing the 1,3,4-thiadiazole moiety were synthesized and characterized by 1H NMR, 13C NMR, spectroscopies HRMS and IR. Among them, the structure of compound 5c (2-(Tert-butyl)?4-chloro-5-((5-((2-ethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was unambiguously confirmed via single crystal X-ray diffraction analysis. The inhibitory activity of all the target compounds against MGC-803 and Bcap-37 was determined by MTT assay, with doxorubicin (the inhibition rates were 95.5 ± 0.4% and 95.7 ± 1.0% respectively) as a control. The preliminary results showed that the inhibitory activity of compound 5n (2-(Tert-butyl)?4-chloro-5-((5-((3-fluorophenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was superior to the others. The inhibition rates of MGC-803 and Bcap-37 cells were 86.3 ± 2.2% and 92.3 ± 0.6% at a concentration of 10 μmol/L, respectively. The preliminary structure-activity relationship showed that when the 2-position of the benzene ring was substituted by a methyl group, such as compound 5j (2-(Tert-butyl)?4-chloro-5-((5-((2,3-dimethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), it exhibited good anticancer activity on MGC-803 cells. Besides, introducing fluorine, chlorine, or trifluoromethyl group onto the benzene ring, such as compound 5 m (2-(Tert-butyl)?4-chloro-5-((5-((4-(trifluoromethoxy)phenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), displayed good anticancer activity on MGC-803 and Bcap-37 cells.
- Qin, Junhu,Zhu, Mei,Zhu, Hongmei,Zhang, Liqiong,Fu, Yihong,Liu, Jiamin,Wang, Zhenchao,OuYang, Guiping
-
p. 592 - 599
(2020/03/16)
-
- Direct, Microwave-Assisted Synthesis of Isothiocyanates
-
A microwave-assisted desulfuration of readily available dithiocarbamates, formed in situ from primary amines, leading to target isothiocyanates has been developed. This efficient protocol provides a rapid, environmentally benign route to aliphatic and aromatic isothiocyanates.
- Janczewski, ?ukasz,Gajda, Anna,Gajda, Tadeusz
-
supporting information
p. 2528 - 2532
(2019/04/03)
-
- A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: A mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates
-
A new multicomponent reaction has been developed between isocyanides, sulfur and alcohols or thiols under mild reaction conditions to afford O-thiocarbamates and dithiocarbamates in moderate to good yields. The one-pot reaction cascade involves the formation of an isothiocyanate intermediate, thus a catalyst-free synthesis of isothiocyanates, as valuable building blocks from isocyanides and sulfur is proposed, as well. The synthetic procedure suits the demand of a modern organic chemist, as it tolerates a wide range of functional groups, it is atom economic and easily scalable.
- Németh, András Gy?rgy,Keseru, Gy?rgy Miklós,ábrányi-Balogh, Péter
-
supporting information
p. 1523 - 1533
(2019/08/07)
-
- Chemical synthesis method of 2,6-dimethylaniline thiazine
-
The invention discloses a chemical synthesis method of 2,6-dimethylaniline thiazine. The method comprises the following steps: dissolving dried acetyl (2,6-dimethyl) aniline into an anhydrous solution; carrying out quantitative reaction on a mixed solution and carbon disulfide under the action of metal hydride to generate isothiocyanic acid-2,6-dimethyl phenyl ester; carrying out aminolysis on theisothiocyanic acid-2,6-dimethyl phenyl ester and 3-aminopropanol to obtain 1-(2,6-dimethyl)-phenyl-3-propanolyl thiourea after drying and purifying; and catalyzing and cyclizing with concentrated hydrochloric acid to obtain a target product 2,6-dimethylaniline thiazine. The preparation method disclosed by the invention has the advantages of easily-obtained raw materials, rigorous requirements onoperating conditions, simplicity in actual production and suitability for industrial mass production.
- -
-
Paragraph 0027-0056
(2019/01/16)
-
- Reaction of Thiocarbonyl Fluoride Generated from Difluorocarbene with Amines
-
The reaction of thiocarbonyl fluoride, generated from difluorocarbene, with various amines under mild conditions is described. Secondary amines, primary amines, and o-phenylenediamines are converted to thiocarbamoyl fluorides, isothiocyanates, and difluoromethylthiolated heterocycles, respectively. Thiocarbamoyl fluorides were further transformed into trifluoromethylated amines by using a one-pot process. Thiocarbonyl fluoride is generated in situ and is rapidly fully converted in one pot under mild conditions; therefore, no special safety precautions are needed.
- Yu, Jiao,Lin, Jin-Hong,Xiao, Ji-Chang
-
supporting information
p. 16669 - 16673
(2017/12/07)
-
- NOVEL FLAVONE BASED EGFR INHIBITORS AND PROCESS FOR PREPARATION THEREOF
-
The present invention discloses a novel EGFR inhibitor compound of formula (1), process for preparation thereof and methods of treating abnormal cell growth in mammals by administering the compounds of formula (1). wherein, R is selected from hydrogen, alkyl, nitro, halogens such as chlorine, bromine, fluorine and iodine; Rl= hydrogen, alkyl, alkoxy, aryl, nitro, halogens such as chlorine, bromine, fluorine and iodine, trifluoromethyl, thioalkyl, trifluromethoxy, trialkylsilyl.
- -
-
Page/Page column 13; 14
(2016/09/22)
-
- PESTICIDALLY ACTIVE SEMI-CARBAZONES AND THIOSEMICARBAZONES DERIVATIVES
-
Compounds of formula (I), wherein the substituents are as defined in claim 1, and agrochemically acceptable salts and enantiomers thereof, can be used as insecticides.
- -
-
Page/Page column 48
(2016/08/17)
-
- Double three bromo 1,3-di-pyridine salt-based propane and its preparation method, method of use, recovery method and application
-
The invention discloses a double tribromo 1,3-bipyridine onium salt dimethylmethane, and a preparation method, an application method, a recovery method and application thereof. The preparation method comprises the following steps: dissolving 1,3-bipyridine onium salt dimethylmethane by using water, and then adding potassium bromide; adding potassium peroxymonosulfate sulfate compound brine solution to prepare a clear solution after dissolving potassium bromide, and then stirring and reacting at -10 to 0 DEG C until solid is separated out; separating out solid, so as to obtain the double tribromo 1,3-bipyridine onium salt dimethylmethane. The product can be used for preparing isothiocyanate, aromatic thiourea or acetanilide. The preparation method disclosed by the invention is mild in condition, and simple to operate the reaction process, and raw materials are easily available. The double tribromo 1,3-bipyridine onium salt dimethylmethane not only can be used as a brominating reagent, but also can be used as organic synthesis intermediates, meanwhile, the reaction efficiency is improved, and the double tribromo 1,3-bipyridine onium salt dimethylmethane is convenient to recover and can be recycled.
- -
-
Paragraph 0150; 0151
(2016/10/07)
-
- Synthesis, acetylcholinesterase and alkaline phosphatase inhibition of some new 1,2,4-triazole and 1,3,4-thiadiazole derivatives
-
A new series of 4,5-disubstituted-2,4-dihydro-3H-1,2,4-triazole-3-thiones (6as) and 2,5-disubstituted-1,3,4-thiadiazoles (7ah) was synthesized by intramolecular dehydrocyclization of various 1,4-disubstituted thiosemicarbazide derivatives (5as) by refluxing in 4N aqueous sodium hydroxide and by overnight stirring with polyphosphoric acid, respectively. The structures of these compounds were characterized by IR, 1H and 13C NMR, elemental analysis and mass spectroscopic studies. All the synthesized compounds were screened for their acetylcholinesterase and alkaline phosphatase inhibition studies. Most of the tested compounds showed promising activities, amongst them (6k) and (6q) showed excellent acetylcholinesterase inhibitory activity with IC50 0.2410.012 and 0.2600.013M, respectively, as compared with those of standard drug whereas the compound (6p), with IC50 0.0440.001M, was found to be the most potent inhibitor of alkaline phosphatase.
- Khan, Imtiaz,Hanif, Muhammad,Rama, Nasim Hasan,Hussain, Muhammad Tahir,Khan, Aftab Ahmed,Aslam, Muhammad Adil S.,Iqbal, Jamshed
-
p. 1413 - 1419,7
(2020/09/02)
-
- Synthesis, antioxidant activities and urease inhibition of some new 1,2,4-triazole and 1,3,4-thiadiazole derivatives
-
New series of 4,5-disubstituted-2,4-dihydro-3H-1,2,4-triazole-3-thiones (8a-j) and 2,5-disubstituted-1,3,4-thiadiazoles (9a-h) were synthesized by dehydrative cyclization of hydrazinecarbothioamide derivatives (7a-k) by refluxing in 4 N aqueous sodium hydroxide and by overnight stirring with polyphosphoric acid, respectively. The structures of the newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, elemental analysis and mass spectroscopic studies and the synthesized compounds were screened for their antioxidant and urease inhibition activities. N-(2,4-Dimethylphenyl)-5-(4-nitrophenyl)-1,3,4-thiadiazol-2-amine (9h) showed excellent antioxidant activity more than the standard drug whereas 4-(2,4-dimethylphenyl)-5-(3-nitrophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (8d) and 4-(2,3-dimethylphenyl)-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (8e) exhibited potent urease inhibitory activities.
- Khan, Imtiaz,Ali, Sajid,Hameed, Shahid,Rama, Nasim Hasan,Hussain, Muhammad Tahir,Wadood, Abdul,Uddin, Reaz,Ul-Haq, Zaheer,Khan, Ajmal,Ali, Sajjad,Choudhary, M. Iqbal
-
scheme or table
p. 5200 - 5207
(2011/01/04)
-
- Molecular iodine mediated preparation of isothiocyanates from dithiocarbamic acid salts
-
We have developed a general economical and environmentally benign method for the preparation of isothiocyanates from the corresponding dilhiocarbamic acid salts by using cheap and readily available reagent molecular iodine. This is perhaps the most efficient method reported so far for the synthesis of isothiocyanates. The reagent is easily available and nontoxic, and the precipitated sulfur can be removed easily; hence, this method is most suitable for large-scale synthesis. Wiley-VCH Verlag GmbH & Co. KGaA.
- Nath, Jayashree,Ghosh, Harisadhan,Yella, Mamesh,Patel, Bhisma K.
-
experimental part
p. 1849 - 1851
(2009/08/07)
-
- Desulfurization mediated by hypervalent iodine(III): A novel strategy for the construction of heterocycles
-
The desulfurization ability of diacetoxyiodobenzene (DIB) has been explored in the preparation of isothiocyanates from the corresponding dithiocarbamate salts. The in situ generated isothiocyanates reacted with o-phenylenediamine and o-aminophenol to form monothioureas, which, on treatment with a further equivalent of DIB in one pot, gave benzimidazoles and aminobenzoxazoles, respectively. Aliphatic 1,2-diamines on reaction with 2 equiv. of isothiocyanate followed by treatment with DIB gave imidazolidenecarbothioamides, whereas the treatment of aromatic 1,2-diaminebis(thioureas) yielded benzimidazoles with the concurrent formation of isothiocyanate. The driving force for the formation of the latter is the aromatization of the product. The use of DIB makes these methods simpler and more efficient, giving high yields of the desired products in one pot. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Ghosh, Harisadhan,Yella, Ramesh,Nath, Jayashree,Patel, Bhisma K.
-
scheme or table
p. 6189 - 6196
(2009/05/27)
-
- Method for treating central nervous system disorders with substituted 2-imidazoline derivatives
-
The present invention relates to a method for treating depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders which comprises administering to an individual a therapeutically effective amount of a compound of formula I wherein R, X, A, and n are as defined in the specification and pharmaceutically active salts, racemic mixtures, enantiomers, optical isomers and tautomeric forms thereof.
- -
-
Page/Page column 4
(2008/06/13)
-
- Copper(I)/S8 reversible reactions leading to an end-on bound dicopper(II) disulfide complex: Nucleophilic reactivity and analogies to copper-dioxygen chemistry
-
Elemental sulfur (S8) reacts reversibly with the copper(I) complex [(TMPA′)CuI]+ (1), where TMPA′ is a TMPA (tris(2-pyridylmethyl)amine) analogue with a 6-CH2OCH 3 substituent on one pyridyl ligand arm, affording a spectroscopically pure end-on bound disulfido-dicopper(II) complex [{(TMPA′)CuII}2(μ-1,2-S2 2-)]2+ (2) {ν(S-S) = 492 cm-1; ν(Cu-S)sym = 309 cm-1}; by contrast, [(TMPA)Cu I(CH3CN)]+ (3)/S8 chemistry produces an equilibrium mixture of at least three complexes. The reaction of excess PPh3 with 2 leads to formal "release" of zerovalent sulfur and reduction of copper ion to give the corresponding complex [(TMPA′)-CuI(PPh3)]+ (11) along with S=PPh3 as products. Dioxygen displaces the disulfur moiety from 2 to produce the end-on Cu2O2 complex, [{(TMPA′)Cu II}2(μ-1,2-O22-)]2+ (9). Addition of the tetradentate ligand TMPA to 2 generates the apparently more thermodynamically stable [{(TMPA)CuII}2(μ-1,2-S 22-)]2+ (4) and expected mixture of other species. Bubbling 2 with CO leads to the formation of the carbonyl adduct [(TMPA′)CuI-(CO)]+ (8). Carbonylation/sulfur- release/CO-removal cycles can be repeated several times. Sulfur atom transfer from 2 also occurs in a near quantitative manner when it is treated with 2,6-dimethylphenyl isocyanide (ArNC), leading to the corresponding isothiocyanate (ArNCS) and [(TMPA′)CuI(CNAr)]+ (12). Complex 2 readily reacts with PhCH2Br: [{(TMPA′)Cu II}2(μ-1,2-S22-)]2+ (2) + 2 PhCH2Br → [{(TMPA′)-CuII(Br)} 2]2+ (6) + PhCH2SSCH2Ph. The unprecedented substrate reactivity studies reveal that end-on bound μ-1,2-disulfide-dicopper(II) complex 2 provides a nucleophilic S 22- moiety, in striking contrast to the electrophilic behavior of a recently described side-on bound μ-η2: η2-disulfido-dicopper(II) complex, [{(N3)Cu II}2(μ-η2:η2-S 22-)]2+ (5) with tridentate N3 ligand. The investigation thus reveals striking analogies of copper/sulfur and copper/dioxygen chemistries, with regard to structure type formation and specific substrate reactivity patterns.
- Maiti, Debabrata,Woertink, Julia S.,Vance, Michael A.,Milligan, Ashley E.,Narducci Sarjeant, Amy A.,Solomon, Edward I.,Karlin, Kenneth D.
-
p. 8882 - 8892
(2008/02/09)
-
- 2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 1: Discovery of CB2 receptor selective compounds
-
2-Arylimino-5,6-dihydro-4H-1,3-thiazines have been identified as a novel class of cannabinoid agonists. A lead structure with moderate activity was discovered through a high throughput screening assay. Structure-activity relationships led to the discovery of potent agonists of CB2 receptor. The most potent compound 13 displays Ki values of >5000 and 9 nM to CB1 and CB2 receptors, respectively.
- Kai, Hiroyuki,Morioka, Yasuhide,Murashi, Takami,Morita, Koichi,Shinonome, Satomi,Nakazato, Hitoshi,Kawamoto, Keiko,Hanasaki, Kohji,Takahashi, Fumiyo,Mihara, Shin-ichi,Arai, Tohko,Abe, Kohji,Okabe, Hiroshi,Baba, Takahiko,Yoshikawa, Takayoshi,Takenaka, Hideyuki
-
p. 4030 - 4034
(2008/02/08)
-
- Rhodium-catalyzed synthesis of isothiocyanate from isonitrile and sulfur
-
Rhodium complexes RhH(PPh3)4 and Rh(acac)(CH 2CH2)2 catalyze sulfuration of isonitrile with sulfur giving isothiocyanates in high yields. The metal-catalyzed reaction is rapid in refluxing acetone, and completes within 3 h in most cases. The reaction exhibits induction period, which disappeared by preheating sulfur in refluxing acetone for 1.5 h. Use of several organic polysulfides in this transformation was examined in order to compare the reactivity.
- Arisawa, Mieko,Ashikawa, Masanori,Suwa, Atsushi,Yamaguchi, Masahiko
-
p. 1727 - 1729
(2007/10/03)
-
- Direct synthesis of isothiocyanates from isonitriles by molybdenum-catalyzed sulfur transfer with elemental sulfur
-
The direct molybdenum-catalyzed sulfuration of a variety of isonitriles with elemental sulfur or propene sulfide as sulfur donors affords the corresponding isothiocyanates in good yields and under mild reaction conditions. A catalytic cycle is suggested, in which the molybdenum oxo disulfur complex operates as the active sulfur-transferring species. A novel adduct between the isonitrile and the molybdenum complex has been characterized by X-ray analysis and its association constant determined by UV-vis spectroscopy, but this adduct appears not to be involved in the sulfur-transfer process.
- Adam, Waldemar,Bargon, Rainer M.,Bosio, Sara G.,Schenk, Wolfdieter A.,Stalke, Dietmar
-
p. 7037 - 7041
(2007/10/03)
-
- Process of preparing an isothiocyanate intermediate used in the preparation of xylazine
-
A process for preparing 2,6-dimethylphenylisothiocyanate comprises the steps of dissolving 2,6-dimethylaniline in carbon disulfide and ammonium hydroxide to form a dithiocarbamate salt. The salt is reacted with ethyl chloroformate to form 2,6-dimethylphenylisothiocyanate, which may thereafter be reacted with 3-amino-1-propanol and subsequently cyclized, by treating with hydrochloric acid, to form xylazine.
- -
-
-
- Novel selenium catalyzed synthesis of isothiocyanates from isocyanides and elemental sulfur
-
A variety of aliphatic and aromatic isothiocyanates were synthesized in good to excellent yields from corresponding isocyanides and elemental sulfur under mild conditions by use of catalytic amounts of elemental selenium.
- Fujiwara, Shin-Ichi,Shin-Ike, Tsutomu,Sonoda, Noboru,Aoki, Minoru,Okada, Kazuhiro,Miyoshi, Noritaka,Kambe, Nobuaki
-
p. 3503 - 3506
(2007/10/02)
-
- Process for the production of xylazine
-
In the preparation of 2,6-dimethylphenylisothiocyanate by reacting N-(2,6-dimethylphenyl)acetamide with sodium hydride in an organic solvent to form the corresponding anion of said amide, then reacting carbon disulfide with said anion to form said 2,6-dimethylphenylisothiocyanate, unexpectedly high yields are obtained by using as the organic solvent tetrahydrofuran or a mixture of N,N-dimethylacetamide and toluene. 2,6-Dimethylphenylisothiocyanate is an intermediate in the preparation of xylazine useful, for instance, as a sedative, an analgesic and muscle relaxant.
- -
-
-
- Studies on organophosphorus compounds. XLV. Thiation of some sterically hindered N-nitrosamides
-
Some sterically hindered N-nitrosamides have been prepared using sodium nitrite in aqueous acid solution.Reaction of these N-nitrosamides with 2,4-bis-(4-methoxyphenyl)-1,2,3,4-dithiadiphosphetane-2,4-disulfide (Lawesson's Reagent ) causes thiation of both the carbonyl and the nitroso groups followed by destruction of the nitroso group giving ultimately the corresponding thioamides and amides as the main products.Dihydro-2(3H)-thiophenone is isolated as a by-product when N-nitroso-dihydro-2(3H)-pyrrolidinone is reacted with LR.A mechanism for its formation is postulated.Thiation of the sterically hindered amides yields the thioamide as rotamers which in two cases could be separated by column chromatography.Ames test has been performed for some of the compounds.
- Joergensen, Karl Anker,Ghattas, Abdul-Badik,Lawesson, Sven-Olov
-
p. 204 - 208
(2007/10/02)
-