33904-04-0

Basic information

• Product Name: 3,4-DIMETHOXYPHENYL ISOTHIOCYANATE
• Synonyms: 3,4-DIMETHOXYPHENYL ISOTHIOCYANATE;ISOTHIOCYANIC ACID 3,4-DIMETHOXYPHENYL ESTER;4-Isothiocyanato-1,2-dimethoxybenzene;ISOTHIOCYANIC ACID 3,4-DIMETHOXYPHENYL ESTER 96+%;3,4-Dimethoxyphenyl Isthiocyanate;3,4-Dimethoxyphenyl isothiocyate, 99%
• CAS NO: 33904-04-0
• Molecular Formula: C₉H₉NO₂S
• Molecular Weight: 195.24
• EINECS: -0
• Mol File: 33904-04-0.mol

Chemical Properties

• Melting Point: 47 °C
• Boiling Point: 171 °C
• Flash Point: 171-172°C/7mm
• Appearance: /
• Density: 1.12g/cm³
• Vapor Pressure: 0.00106mmHg at 25°C
• Refractive Index: 1.537
• Sensitive: Moisture Sensitive
• BRN: 2726948
• CAS DataBase Reference: 3,4-DIMETHOXYPHENYL ISOTHIOCYANATE(CAS DataBase Reference)
• NIST Chemistry Reference: 3,4-DIMETHOXYPHENYL ISOTHIOCYANATE(33904-04-0)
• EPA Substance Registry System: 3,4-DIMETHOXYPHENYL ISOTHIOCYANATE(33904-04-0)

Safety Data

• Hazard Codes: Xn:Harmful
• Statements: 20/21/22-36/37/38-34
• Safety Statements: 26-36/37/39-45
• RIDADR: 2810
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 33904-04-0(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
3,4-DIMETHOXYPHENYL ISOTHIOCYANATE is used as a building block in organic synthesis for the creation of various pharmaceuticals, agrochemicals, and other fine chemicals. Its reactivity with nucleophiles makes it a valuable component in the development of new compounds with potential applications in various industries.
Used in Biological Research:
3,4-DIMETHOXYPHENYL ISOTHIOCYANATE is used as a research tool in biological studies due to its ability to react with biomolecules and form covalent bonds. This property allows scientists to develop new tools for studying cellular processes and drug discovery, potentially leading to the creation of novel therapeutic agents and diagnostic methods.
Used in Drug Discovery:
3,4-DIMETHOXYPHENYL ISOTHIOCYANATE is employed in drug discovery as a starting material for the synthesis of new pharmaceutical compounds. Its reactivity and versatility in chemical reactions enable the development of innovative drugs with potential therapeutic benefits in various medical fields.
Used in Agrochemicals:
In the agrochemical industry, 3,4-DIMETHOXYPHENYL ISOTHIOCYANATE is used as a key intermediate in the synthesis of various agrochemicals, such as pesticides and herbicides. Its reactivity and ability to form stable covalent bonds contribute to the development of effective and environmentally friendly agricultural products.

InChI:InChI=1/C9H9NO2S/c1-11-8-4-3-7(10-6-13)5-9(8)12-2/h3-5H,1-2H3

Upstream product

• 16420-13-6 N,N-Dimethylthiocarbamoyl chloride 
• 6315-89-5 3,4-dimethoxyaniline 
• 75-15-0 carbon disulfide 
• 463-71-8 thiophosgene 

Downstream Products

• 895390-48-4 2-[3-(3,4-dimethoxy-phenyl)-thioureido]-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylic acid ethyl ester 
• 65069-52-5 N-[3,4-dimethoxyphenyl]thiourea 

Relevant articles and documents

Discovery of boronic acid-based potent activators of tumor pyruvate kinase M2 and development of gastroretentive nanoformulation for oral dosing

Several studies have established that cancer cells explicitly over-express the less active isoform of pyruvate kinase M2 (PKM2) is critical for tumorigenesis. The activation of PKM2 towards tetramer formation may increase affinity towards phosphoenolpyruvate (PEP) and avoidance of the Warburg effect. Herein, we describe the design, synthesis, and development of boronic acid-based molecules as activators of PKM2. The designed molecules were inspired by existing anticancer scaffolds and several fragments were assembled in the derivatives. 6a-6d were synthesized using a multi-step synthetic strategy in 55–70% yields, starting from cheap and readily available materials. The compounds were selectively cytotoxic to kill the cancerous cells at 80 nM, while they were non-toxic to the normal cells. The kinetic studies established the compounds as novel activators of PKM2 and (E/Z)-(4-(3-(2-((4-chlorophenyl)amino)-4-(dimethylamino)thiazol-5-yl)-2-(ethoxycarbonyl)-3-oxoprop-1-en-1-yl) phenyl)boronic acid (6c) emerged as the most potent derivative. 6c was further evaluated using various in silico tools to understand the molecular mechanism of tetramer formation. Docking studies revealed that 6c binds to the PKM2 dimer at the dimeric interface. Further to ascertain the binding site and mechanism of action, rigorous MD (molecular dynamics) simulations were undertaken, which led to the conclusion that 6c stabilizes the center of the dimeric interface that possibly promotes tetramer formation. We further planned to make a tablet of the developed molecule for oral delivery, but it was seriously impeded owing to poor aqueous solubility of 6c. To improve aqueous solubility and retain 6c at the lower gastrointestinal tract, thiolated chitosan-based nanoparticles (TCNPs) were prepared and further developed as tablet dosage form to retain anticancer potency in the excised goat colon. Our findings may provide a valuable pharmacological mechanism for understanding metabolic underpinnings that may aid in the clinical development of new anticancer agents targeting PKM2.

Synthesis, in-vitro antiprotozoal activity and molecular docking study of isothiocyanate derivatives

Novel isothiocyanate derivatives were synthesized starting from noscapine, bile acids, amino acids, and some aromatic compounds. Antiparasitic activities of the synthesized derivatives were tested against four unicellular protozoa, i.e., Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani, and Plasmodium falciparum. Interestingly, seven isothiocyanate analogues displayed promising antiparasitic activity against Leishmania donovani with IC50 values between 0.4 and 1.0 μM and selectivity index (SI) ranged from 7.8 to 18.4, comparable to the standard drug miltefosine (IC50 = 0.7 μM). Compound 7h demonstrated the best antileishmanial activity with an IC50 value of 0.4 μM. Seven products exhibited inhibition activity against T. brucei rhodesiense with IC50s below 2.0 μM and SI between 2.7 and 29.3. Four primary amine derivatives of noscapine and five isothiocyanate derivatives exhibited antiplasmodial activity with IC50s in the range of 1.1–2.7 μM and SI values between 1.1 and 14.5. The isothiocyanate derivative 7c showed against T. cruzi with an IC50 value of 1.9 μM and SI 4. Molecular docking and ADMET studies were performed to investigate the interaction between active ligands and T. brucei trypanothione reductase active site. The docking studies showed significant binding affinity of noscapine derivatives to enzyme active site and good compatibility with experimental data.

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Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino- and Enteroviruses

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New syntheses of aryl isothiocyanates

Primary aromatic amines are readily converted into arylimino-1,2,3-dithiazoles 2 and the derived cyanothioformanilides 6, both of which are rapidly cleaved by ethylmagnesium bromide in hot THF to give the corresponding isothiocyanates. The transformation 2→6→ArNCS can be performed as a 'one-pot' operation. The imines 2 are also converted, more slowly, into the isothiocyanates by sodium hydride in hot THF, via the cyanothioformanilides 6. Conversion of the anilides 6 into isothiocyanates is much faster under microwave irradiation in 2,6-lutidine. Mechanisms are proposed for these reactions.

New syntheses of aryl isothiocyanates from N-arylimino-1,2,3-dithiazoles

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