622-78-6Relevant articles and documents
4-Amino-1,8-naphthalimide-based anion receptors: Employing the naphthalimide N-H moiety in the cooperative binding of dihydrogenphosphate
Pfeffer, Frederick M.,Buschgens, Alisha M.,Barnett, Neil W.,Gunnlaugsson, Thorfinnur,Kruger, Paul E.
, p. 6579 - 6584 (2005)
The 4-amino-1,8-naphthalimide-based anion receptor 3 binds dihydrogenphosphate with 1:1 stoichiometry through cooperative hydrogen bonding to a naphthalimide N-H and thiourea N-H groups. This was clearly established from 1H NMR titration experiments in DMSO-d6 where a substantial shift in the resonance for the naphthalimide N-H was observed concomitant with the expected thiourea N-H chemical shift migration upon successive additions of H2PO4-. However, whilst 1H NMR titration experiments indicate that 3 was capable of binding other anions such as acetate, the naphthalimide N-H does not participate and the N-H resonance was essentially invariant during the titration. The lack of cooperative binding in this instance was justifiable on steric grounds.
A more sustainable isothiocyanate synthesis by amine catalyzed sulfurization of isocyanides with elemental sulfur
Nickisch,Conen,Gabrielsen,Meier
, p. 3134 - 3142 (2021/01/28)
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
Synthesis of isothiocyanates using DMT/NMM/TsO? as a new desulfurization reagent
Janczewski, ?ukasz,Kolesińska, Beata,Kr?giel, Dorota
, (2021/05/29)
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.
4-Dimethylaminopyridine-catalyzed synthesis of isothiocyanates from amines and carbon disulfide
Rong, Hao-Jie,Chen, Tao,Xu, Ze-Gang,Su, Tian-Duo,Shang, Yu,Wang, Yong-Qiang,Yang, Cui-Feng
, (2021/03/03)
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.
A catalyst-free method for the synthesis of 1,4,2-dithiazoles from isothiocyanates and hydroxylamine triflic acid salts
An, Zhenyu,Liu, Yafeng,Ren, Yi,Wang, Ting,Yan, Rulong
supporting information, p. 6206 - 6209 (2021/07/28)
A catalyst-free method for the preparation of 1,4,2-dithiazoles is developed by reactions of isothiocyanates with hydroxylamine triflic acid salts. This reaction achieves C-S, C-N, and S-N bond formation, and a range of products are obtained in moderate to good yields. The obvious feature is using shelf-stable hydroxylamine triflic acid salts as a N source to synthesize heterocycles under mild conditions.
NaOH-promoted one-pot aryl isothiocyanate synthesis under mild benchtop conditions
Li, Hang,Liu, Xinyun,Yin, Xiaogang
supporting information, p. 839 - 844 (2021/05/27)
In this work, we have established a green synthesis of aryl isothiocyanates promoted by the low-cost and readily available NaOH from aryl amines and carbon disulfide in a one-pot procedure. The developed protocol features no extra desulfurating reagents and mild benchtop conditions, in which NaOH serves as both the base and the desulfurating reagent to decompose the dithiocarbamate intermediate. Fourteen examples of aryl amines bearing electronic neutral, rich and poor substituents, as well as benzylamine, have proved to be compatible substrates in the developed method to furnish the corresponding isothiocyanates. The reaction has been performed on a gram scale to further demonstrate its synthetic utility. Compared to the reported base-promoted synthesis of aryl isothiocyanates that requires the use of special equipment, such as the ball mill or the microwave reactor, the simplicity in operation and scalability enables this method to efficiently access a variety of aryl isothiocyanates.
Design, synthesis, and computational validation of novel compounds selectively targeting HER2-expressing breast cancer
Elseginy, Samia A.,Hamdy, Rania,Menon, Varsha,Almehdi, Ahmed M.,El-Awady, Raafat,Soliman, Sameh S.M.
, (2020/11/09)
Human epidermal growth factor receptor (HER) is a family of multidomain proteins that plays important role in the regulation of several biological functions. HER2 is a member of HER that is highly presented in breast cancer cells. Here, we designed and synthesized a series of diaryl urea/thiourea compounds. The compounds were tested on HER2+ breast cancer cells including MCF-7 and SkBr3, compared to HER2- breast cancer cells including MDA-MB-231 and BT-549. Only compounds 12–14 at 10 μM showed selective anti-proliferative activity against MCF-7 and SkBr3 by 65–79%. Compounds 12–14 showed >80% inhibition of the intracellular kinase domain of HER2. The results obtained indicated that compounds 12–14 are selectively targeting HER2+ cells. The IC50 of compound 13 against MCF-7 and SkBR3 were 1.3 ± 0.009 and 0.73 ± 0.03 μM, respectively. Molecular docking and MD simulations (50 ns) were carried out, and their binding free energies were calculated. Compounds 12–14 formed strong hydrogen bond and pi–pi stacking interactions with the key residues Thr862 and Phe864. 3DQSAR model confirmed the role of 3-bromo substituent of pyridine ring and 4-chloro substituent of phenyl ring in the activity of the compounds. In conclusion, novel compounds, particularly 13 were developed selectively against HER2-expressing/overexpressing breast cancer cells including MCF7 and SkBr3.
Method for preparing isothiocyanate by alkali catalysis
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Paragraph 0057-0061, (2020/11/22)
The invention discloses a method for preparing isothiocyanate by alkali catalysis, which realizes one-step conversion from primary amine to isothiocyanate under the alkali catalysis. The method comprises the following steps: dissolving primary amine in methanol at -20 to 40 DEG C to obtain a primary amine solution, sequentially adding an alkali catalyst, carbon disulfide and an oxidant into the primary amine solution, carrying out stirring reaction, and carrying out reduced pressure distillation; finally, carrying out extraction and column chromatography purification to obtain the product; wherein the molar ratio of the primary amine to the base catalyst to the carbon disulfide to the oxidizing agent is 1: (0.05-0.2) : (2.5-10) : (1.2-4.5), the structural general formula of the primary amine is RNH2, the structural general formula of the isothiocyanate is R-N=C=S, and the R group is alkyl, aryl, benzyl or allyl. Herein, primary amine reacts with carbon disulfide under the action of analkali catalyst and an oxidizing agent to directly generate isothiocyanate, so that sulfur phosgene and excessive alkali are avoided, and the whole reaction atom economy is high, operation is simple.The method is more suitable for preparation of functional organic intermediates and active biomolecules.
Application of sulfur-containing isocyanate compounds in growth inhibition of blue-green algae
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Paragraph 0042-0048, (2020/04/29)
The invention relates to the application of sulfur-containing isocyanate compounds in the growth inhibition of blue-green algae. The compounds have structures as shown in a general formula I and a general formula II. In the general formula I, R1 represents a methyl group, a phenethyl group, a phenyl group, 4-methylpyridine or 3-methylpyridine. In the general formula II, M represents a carbonyl group, a methylene group and a methylene phenyl group; R3 represents hydrogen or chlorine; R4 represents oxygen, hydrogen, fluorine or chlorine; R5 represents oxygen, hydrogen, chlorine, a methyl group,fluorine, a benzene ring, bromine or a trifluoromethyl group; when R4 and R5 are oxygen, R4 and R5 are cyclized to form 1,3-dioxocyclopentene; R6 represents hydrogen, fluorine, bromine, a trifluoromethyl group, a methyl group and chlorine; and R7 represents hydrogen, a trifluoromethyl group, chlorine and bromine. The sulfur-containing isocyanate compounds with the structures as shown in the general formulas I and II provided by the invention have relatively good inhibition effect on blue-green algae, and can be used as an effective component of a blue-green algae algicide.
Thiosemicarbazone-based lead optimization to discover high-efficiency and low-toxicity anti-gastric cancer agents
Bo-Wang,He, Zhang-Xu,Li, Yi-Han,Liu, Hong-Min,Ma, Li-Ying,Ma, Qin,Tao, Yuan-Yuan,Wang, Hao-Jie,Wu, Hui-Pan,Zhang, Xin-Hui,Zhao, Bing
, (2020/05/19)
In this paper, a series of thiosemicarbazone derivatives containing different aromatic heterocyclic groups were synthesized and the tridentate donor system of the lead compound was optimized. Most of the target compounds showed improved antiproliferative activity against MGC803 cells. SAR studies revealed that compound 5d displayed significant advantages in inhibition effect with an IC50 value of 0.031 μM, and better selectivity between cancer and normal cells than 3-AP and DpC (about 15- and 5-fold improved respectively). Besides, compound 5d showed selective antiproliferative activity in not only other cancer cells but also different gastric cancer cell lines. In-depth mechanism studies showed that compound 5d could induce mitochondria-related apoptosis which might be related to the elevation of intracellular ROS level, and cause cell cycle arrest at S phase. Moreover, 5d could evidently suppress the cell migration and invasion by blocking the EMT (epithelial–mesenchymal transition) process. Consequently, our studies provided a lead optimization strategy of thiosemicarbazone derivatives which would contribute to discover high-efficiency and low-toxicity agents for the treatment of gastric cancer.
