551-06-4

Basic information

• Product Name: 1-Naphthyl isothiocyanate
• Synonyms: 1-Isothiocyanatenaphthalene;1-isothiocyanate-naphthalene;1-isothiocyanato-naphthalen;1-Isothiocyanatonaphthalene;1-iso-Thiocyanatonaphthalene;1-Naftylisothiokyanat;1-Naphthalene isothiocyanate;alpha-Naphthysothiocyanate
• CAS NO: 551-06-4
• Molecular Formula: C₁₁H₇NS
• Molecular Weight: 185.24
• EINECS: 208-990-8
• Product Categories: Thiocyanates/IsothiocyanatesDerivatization Reagents;Derivatization Reagents HPLC;Organic Building Blocks;Sulfur Compounds;UV-VIS
• Mol File: 551-06-4.mol

Chemical Properties

• Melting Point: 55.5-57 °C(lit.)
• Boiling Point: 339.3°Cat760mmHg
• Flash Point: 167.2°C
• Appearance: Yellow/Fine Crystalline Powder
• Density: 1.1142 (rough estimate)
• Refractive Index: 1.5500 (estimate)
• Storage Temp.: 2-8°C
• Water Solubility: insoluble
• Sensitive: Moisture Sensitive
• Stability: Stable, but moisture sensitive. Incompatible with strong oxidizing agents.
• Merck: 14,6411
• BRN: 637868
• CAS DataBase Reference: 1-Naphthyl isothiocyanate(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Naphthyl isothiocyanate(551-06-4)
• EPA Substance Registry System: 1-Naphthyl isothiocyanate(551-06-4)

Safety Data

• Hazard Codes: T
• Statements: 20/21-25-36/37/38-42-23/24/25
• Safety Statements: 22-26-36/37-45-24/25
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: NX9100000
• TSCA: Yes
• HazardClass: 6.1
• PackingGroup: II
• Hazardous Substances Data: 551-06-4(Hazardous Substances Data)

Usage

Uses

Used in Insecticides:
1-Naphthyl isothiocyanate is used as an ingredient in insecticides, providing a means to control and manage insect populations.
Used in Industrial Applications:
It is found in cyanamide, which has a wide range of industrial applications, contributing to its versatility in various sectors.
Used in Medical and Drug Studies:
1-Naphthyl isothiocyanate is commonly used in medical and drug studies in animals as a model hepatotoxicant, producing experimental cholestasis in rats and mice. This helps researchers understand the effects of liver damage and develop potential treatments.
Used in the Study of Liver Damage:
1-Naphthyl isothiocyanate serves as a tool for studying liver damage, which can cause bile stasis and hyperbilirubinemia acutely, as well as bile duct hyperplasia and biliary cirrhosis chronically, with changes in hepatocyte function.
Used in Chemical Synthesis:
1-Naphthyl isothiocyanate (NITC) can be used as a source of the thiourea moiety to synthesize derivatives of calix[4]arenes, which are utilized as anion acceptors. Additionally, it is used for the synthesis of naphthyl-substituted 1,2,4-triazoles and 1,3,4-thiadiazoles, further expanding its applications in the chemical industry.

Air & Water Reactions

1-Naphthyl isothiocyanate is moisture sensitive. . Undergoes slow hydrolysis. Insoluble in water.

Reactivity Profile

Isocyanates and thioisocyanates, such as 1-Naphthyl isothiocyanate, are incompatible with many classes of compounds, reacting exothermically to release toxic gases. Reactions with amines, aldehydes, alcohols, alkali metals, ketones, mercaptans, strong oxidizers, hydrides, phenols, and peroxides can cause vigorous releases of heat. Acids and bases initiate polymerization reactions in these materials. Some isocyanates react with water to form amines and liberate carbon dioxide. Base-catalysed reactions of isocyanates with alcohols should be carried out in inert solvents. Such reactions in the absence of solvents often occur with explosive violence, [Wischmeyer(1969)].

Fire Hazard

Flash point data for 1-Naphthyl isothiocyanate is not available, but 1-Naphthyl isothiocyanate is probably combustible.

Environmental Fate

Naphthylisothiocyanate is moisture sensitive and insoluble in water. The hydrolysis rate is slow.

Purification Methods

Crystallise the isothiocyanate from hexane (1g in 9 mL). It forms white needles and is soluble in most organic solvents but is insoluble in H2O. It is absorbed through the skin and may cause dermatitis. [Cymmerman-Craig et al. Org Synth Coll Vol IV 700 1963, Beilstein 12 H 1244, 12 III 2948.]

Toxicity evaluation

1-Naphthylisothiocyanate causes separation of extracellular tight junctions that seal bile canaliculi, impairing bile formation. 1-Naphthylisothiocyanate inhibits microsomal drug-metabolizing activity. In rats, 1-naphthylisothiocyanteglutathione complex is formed in hepatocytes, then transported to the bile ducts, where it is released from the glutathione, and then selectively injures biliary epithelial cells, resulting in reduced bile flow.

InChI:InChI=1/C11H7NS/c13-8-12-11-7-3-5-9-4-1-2-6-10(9)11/h1-7H

Upstream product

• 1240-37-5 N,N'-bis(1-naphthyl)thiourea 
• 75-15-0 carbon disulfide 
• 40168-13-6 1-<(Triphenylphosphoranylidene)amino>naphthalene 
• 463-71-8 thiophosgene 
• 134-32-7 1-amino-naphthalene 
• 103-72-0 phenyl isothiocyanate 
• 86-84-0 1-Naphthyl isocyanate 
• 108-90-7 chlorobenzene 
• 86-88-4 naphthalen-1-yl-thiourea 
• 20979-20-8 Ethyl-1-naphthyldithiocarbamat 
• 13037-43-9 S-methyl-N-(naphthalen-1-yl)carbamodithioate 
• 4921-84-0 N-(naphthalen-1-ylcarbamothioyl)benzamide 
• 15867-07-9 N-(α-naphthyl)dithiocarbamic acid 
• 96989-50-3 di-2-pyridyl thionocarbonate 

Downstream Products

• 103151-81-1 1-cyclohexyl-3-(naphthalen-1-yl)thiourea 
• 51074-83-0 N-[1]naphthyl-N'-(4-sulfamoyl-phenyl)-thiourea 
• 2742-61-2 1,1,-dimethyl-3-(1-naphthyl)-2-thiourea 
• 24775-57-3 1-naphthalen-1-yl-3-phenyl-thiourea 
• 2078-93-5 N-(naphthalen-1-yl)-2-phenylhydrazine-1-carbothioamide 
• 4845-64-1 1H-naphtho[1,2-d]thiazole-2-thione 
• 111782-22-0 1-naphthalen-1-yl-3-o-tolyl-thiourea 
• 107544-71-8 1-benzyl-3-(naphthalen-1-yl)thiourea 

Relevant articles and documents

Design, synthesis, and biological evaluation of novel substituted thiourea derivatives as potential anticancer agents for NSCLC by blocking K-Ras protein-effectors interactions

Mutation of the proto-oncogene K-Ras is one of the most common molecular mechanisms in non-small cell lung cancer. Many drugs for treating lung cancer have been developed, however, due to clinical observed K-Ras mutations, corresponding chemotherapy and targeted therapy for such mutation are not efficient enough. In this study, on the basis of the crystal structure of K-Ras, 21 analogues (TKR01–TKR21) containing urea or thiourea were rationally designed, which can effectively inhibit the lung cancer cell A549 growth. The designing of these compounds was based on the structure of K-Ras protein, and the related groups were replaced by bioisosteres to improve the affinity and selectivity. Biological testing revealed that compound TKR15 could significantly inhibit the proliferation of A549 cell with IC50 of 0.21 μM. Docking analysis showed that the TKR15 can effectively bind to the hydrophobic cavity and form a hydrogen bond with the Glu37. In addition, through flow apoptosis assay and immunofluorescence staining assay, it confirmed that this compound can inhibit A549 cell proliferation with the mechanism of blocking K-RasG12V protein and effector proteins interactions through the apoptotic pathway. In conclusion, our studies in finding novel potent compound (TKR15) with confirmed mechanism showed great potential for further optimisation and other medicinal chemistry relevant studies.

Synthesis and biological evaluation of innovative thiourea derivatives as PHGDH inhibitors

In order to discover novel compounds with inhibitory activity against 3-phosphoglycerate dehydrogenase (PHGDH), a series of thiourea derivatives were designed and synthesized based on the structural modification of compound 5d. Compound 5d emerged from the visual database of ChemDiv of 200,000 small molecules by docking score ranking. Inhibition experiments on PHGDH activity of newly synthesized compounds were performed in vitro. Compounds with more than 30percent inhibitory rate at 25?μM on PHGDH were screened for IC50 measurement. Anti-proliferative activity of 4a, 5a, 6e, 6n against A2780, MDA-MB-468, MDA-MB-231 and HEK293T in vitro was evaluated. The results showed that the compound 4a displayed the best inhibitory activity on PHGDH among the newly synthesized compounds, and the compounds 4a, 5a, 6n had a better proliferation inhibition effect on human A2780 cell line than NCT-503 reported previously. In addition, 2D interaction diagrams revealed potential action modes of active compounds with PHGDH.

Organophosphine-free copper-catalyzed isothiocyanation of amines with sodium bromodifluoroacetate and sulfur

A copper-catalyzed isothiocyanation of amines with sodium bromodifluoroacetate and sulfur in the absence of organophosphine has been established. This approach represents a simple and efficient one-pot synthesis of isothiocyanates, and features excellent functional group tolerance and the use of a cheap, safe and odorless sulfur source. Moreover, this process could directly provide isothiocyanate analogous bioactive molecules, thiocarbonyl-containing pesticides and facile construction of benzoxazole and benzimidazole frames.

Isothiocyanate synthesized by three components and preparation method of isothiocyanate

The invention discloses isothiocyanate and a preparation method thereof. The method comprises the steps that primary amine, sodium difluorobromoacetate and elemental sulfur are taken as reactants forreaction; the reaction is carried out under the action of a copper catalyst, wherein the copper catalyst is any one of cuprous chloride, copper bromide, cuprous iodide, copper chloride and copper trifluoromethanesulfonate; an alkali is also added, wherein the alkali is any one of sodium bicarbonate, potassium carbonate, cesium carbonate, potassium phosphate, DABCO and sodium tert-butoxide; the whole reaction is carried out in a solvent, wherein the solvent is acetonitrile or dimethyl sulfoxide, the reaction temperature is 80-120 DEG C, and the reaction time is 10-14 hours. The method can directly synthesize the target product, does not need to separate intermediate products and only needs stirring and heating reaction under normal pressure to obtain the target product, and the yield can beup to 87%; a waste solution is fewer during the reaction, and the method protects the environment and ensures the health of an operator; in addition, a series of isothiocyanate derivatives can be prepared, and the method has a stronger substrate universality.

Na2S2O8-mediated efficient synthesis of isothiocyanates from primary amines in water

We have developed two green, practical, and efficient procedures, including a one-pot one, to synthesize isothiocyanates from amines and carbon disulfide via desulfurization with sodium persulfate. Water is used as the solvent. Basic conditions are necessary for good chemoselectivity for isothiocyanates. Structurally diverse linear and branched alkyl amines and aryl amines are readily converted to isothiocyanates by the two procedures in satisfactory yields. Halogens, benzylic C-H bonds, methylthio, nitro, ester, alkenyl, electron-rich or -deficient (hetero)aryls, acetylenyl, and even phenolic and alcoholic hydroxyls are well tolerated. The one-pot procedure in water can also be used to realize the preparation of chiral isothiocyanates from chiral amines, and the modification of bioactive structures with free amino groups. In large-scale preparation, simple and practical purification procedures independent of column chromatography are developed.

Alkali-free green synthetic isothiocyanate method

The invention discloses an alkali-free green synthetic method for isothiocyanate, and relates to the field of organic chemical industry. The method includes the steps: (1) adding solvents into carbon sulfide reagents and primary amine serving as raw materials, performing organic reaction at the temperature of 100-150 DEG C for 10-30 hours; (2) cooling and spin-drying the raw materials after reaction, adding dichloromethane, extracting and separating organic phases by 10% of dilute hydrochloride acid, washing the organic phases, combining the organic phases into an organic layer, washing the organic layer with saturated salt water, drying the organic layer by anhydrous Na2SO4, and performing column chromatographic separation to obtain the isothiocyanate. The molar ratio of the carbon sulfide reagents to the primary amine is 1:1.2-3. Compared with a preparation method in the prior art, the method has the advantages that only heating reaction needs to be performed in the solvents, additional alkali is omitted, and the method is greener and more environmentally friendly and has better application values.

Synthesis, structure-activity relationship and binding mode analysis of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase

A series of 4-thiazolidinone derivatives were synthesized and evaluated as novel human dihydroorotate dehydrogenase (hDHODH) inhibitors. Compounds 26 and 31 displayed IC50 values of 1.75 and 1.12 μM, respectively. The structure-activity relationship was summarized. Further binding mode analysis revealed that compound 31 could form a hydrogen bond with Tyr38 and a water-mediated hydrogen bond with Ala55, which may be necessary for maintaining the bioactivities of the compounds in this series. Further structural optimization of the para- or meta-position of the phenyl group at R will lead to the identification of more potent hDHODH inhibitors.

Isothiocyanation of amines using the Langlois reagent

The Langlois reagent was found to be effective for the isothiocyanation of primary amines in the presence of copper iodide and diethyl phosphonate.

Aminobenzimidazoles and Structural Isomers as Templates for Dual-Acting Butyrylcholinesterase Inhibitors and hCB2R Ligands To Combat Neurodegenerative Disorders

A pharmacophore model for butyrylcholinesterase (BChE) inhibitors was applied to a human cannabinoid subtype 2 receptor (hCB2R) agonist and verified it as a first-generation lead for respective dual-acting compounds. The design, synthesis, and pharmacological evaluation of various derivatives led to the identification of aminobenzimidazoles as second-generation leads with micro- or sub-micromolar activities at both targets and excellent selectivity over hCB1and AChE, respectively. Computational studies of the first- and second-generation lead structures by applying molecular dynamics (MD) on the active hCB2R model, along with docking and MD on hBChE, has enabled an explanation of their binding profiles at the protein levels and opened the way for further optimization. Dual-acting compounds with “balanced” affinities and excellent selectivities could be obtained that represent leads for treatment of both cognitive and pathophysiological impairment occurring in neurodegenerative disorders.