86-88-4

Usage

Uses

Used in Pest Control Industry:
1-(1-NAPHTHYL)-2-THIOUREA is used as a single-dose rodenticide specifically for controlling adult Norway rats as a bait. It is less toxic to other rat species and was once popular due to its specificity towards Norway rodents. However, due to its tendency to cause resistance and limited effectiveness against other rodent species, ANTU has lost popularity and is no longer manufactured in the United States.

Air & Water Reactions

Slightly soluble in water.

Reactivity Profile

1-(1-NAPHTHYL)-2-THIOUREA is incompatible with the following: Strong oxidizers, silver nitrate .

Health Hazard

Moderately toxic: probable oral lethal dose (human) 0.5-5 gm/kg, or between 1 ounce and 1 pint (or l lb.) for 150 lb. person. Chronic sublethal exposure may cause antithyroid activity. Can produce hyperglycemia of three times normal in three hours. People with chronic respiratory disease or liver disease may be especially at risk.

Health Hazard

α-Naphthalene thiourea, a rodenticide, is very toxic and is fatal if swallowed. Exposures to ANTU cause poisoning with symptoms that include, but are not limited to, headache, weakness, dizziness, shortness of breath, cyanosis, blood abnormalities, methemoglobinemia, irritation of the digestive tract, liver and kidney damage, cardiac and CNS disturbances, convulsions, tachycardia, dyspnea, vertigo, tinnitus, weakness, disorientation, lethargy, drowsiness, and fi nally coma and death. The target organs include the blood, kidneys, CNS, liver, lungs, cardiovascular system, and blood-forming organs.

Fire Hazard

Emits sulfur dioxide, oxides of nitrogen, and carbon monoxide fumes upon decomposition. 1-(1-NAPHTHYL)-2-THIOUREA reacts with silver nitrate and strong oxidizers. Avoid decomposing heat.

Safety Profile

Poison by ingestion and intraperitoneal routes. Moderately toxic to humans by an unspecified route. Questionable carcinogen with experimental tumorigenic data. Mutagenic data. A rodenticide used extensively. Death is caused by pulmonary edema. Chronic toxicity has been known to cause dermatitis and a decrease in the white blood cells. When heated to decomposition it emits toxic fumes of NOx and SOx.

Potential Exposure

ANTU or its formulations are used as a rodenticide.

Carcinogenicity

ANTU was not carcinogenic in rodent feeding studies.4 Cases of bladder tumors among rat catchers exposed to ANTU have been attributed to b-naphthylamine, a manufacturing impurity of ANTU. In bacterial assays ANTU induced mutations.

Environmental Fate

Chemical/Physical. The hydrolysis rate constant for ANTU at pH 7 and 25°C was determined to be 8 × 10–5/hour, resulting in a half-life of 361 days (Ellington et al., 1988)Emits very toxic fumes of nitrogen and sulfur oxides when heated to decomposition (Lewis, 1990)

storage

α-Naphthalene thiourea should be kept stored in a tightly closed container in a locked poison room, in a cool, dry, well-ventilated area away from incompatible substances.

Shipping

UN1651 Naphthylthiourea, Hazard Class: 6.1; Labels: 6.1-Poisonous materials.

Purification Methods

Crystallise ANTU from EtOH. [Beilstein 12 III 2941, 12 IV 3086.]

Toxicity evaluation

ANTU toxicity in the rat is thought to depend on metabolic activation via the hepatic and lung microsomal enzymes. Two important metabolites are formed: ANU and atomic sulfur. ANTU pulmonary toxicity may result, in part, from covalent binding of sulfur or a metabolite containing carbonyl carbon of ANTU to macromolecules of liver and lung microsomes. The covalent binding of atomic sulfur released in the cytochrome P450 monooxygenase-catalyzed metabolism of thiono-sulfur compounds is responsible for monooxygenase activity being inhibited. Damage to liver and possibly lung edema and neoplasia result from the covalent binding of the electrophilic S-oxides, S-dioxides or carbene derivatives of these S-oxides and S-dioxides to tissue macromolecules. However, it is not known if these metabolites are seen in humans. ANTU is believed to act on certain enzyme systems involving the sulfhydryl group similar to other sulfhydryl inhibitors, such as alloxan, iodoacetamide, and oxophenarsine, which cause pulmonary edema. Hence the mechanism of action of causing pulmonary edema from the toxic effects of these sulfhydryl inhibitors and ANTU is assumed to be similar. Additionally, ANTU-induced lung damage has been linked to the formation of oxygen free radicals produced via the cyclooxygenase pathway. Following exposure to ANTU, there are a number of biochemical events, such as alteration in carbohydrate metabolism, adrenal stimulation, and interaction of the chemical with sulfhydryl groups, but none of these appear to bear any relationship to the observed signs of toxicity.

Incompatibilities

Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides, silver nitrate.

Waste Disposal

Incinerate in a furnace equipped with an alkaline scrubber. Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste containing this contaminant (≥100 kg/mo) must conform with EPA regulations governing storage, transportation, treatment, and waste disposal.

Precautions

Workers should use/handle α-naphthalene thiourea with adequate ventilation. During use, dust generation and accumulation should be minimum, and avoid contact with the eyes, skin, and clothing.

InChI:InChI=1/C11H10N2S/c12-11(14)13-10-7-3-5-8-4-1-2-6-9(8)10/h1-7H,(H3,12,13,14)

Upstream product

• 14185-62-7 N-acetyl-N'-[1]naphthyl-thiourea 
• 1147550-11-5 ammonium thiocyanate 
• 134-32-7 1-amino-naphthalene 
• 551-06-4 1-isothiocyanatonaphthalene 
• 532-55-8 Benzoyl isothiocyanate 
• 7732-18-5 water 
• 333-20-0 potassium thioacyanate 
• 67-66-3 chloroform 
• 1636-33-5 2-naphthyl isothiocyanate 
• 17356-08-0 thiourea 
• 1078157-23-9 1-(N-(1-naphthyl)thiocarbamoyl)-1H-benzotriazole 
• 43039-14-1 C₆H₁₅N*C₁₁H₉NS₂ 
• 552-46-5 1-naphthylamine hydrochloride 
• 4921-84-0 N-(naphthalen-1-ylcarbamothioyl)benzamide 

Downstream Products

• 398996-75-3 2-[1]naphthylamino-thiazol-4-one 
• 551-06-4 1-isothiocyanatonaphthalene 
• 1843-13-6 [1]naphthyl-(4-phenyl-thiazol-2-yl)-amine 
• 78864-07-0 [5-(4-fluoro-phenyl)-thiazol-2-yl]-naphthalen-1-yl-amine 
• 78864-17-2 [5-(2-fluoro-5-methyl-phenyl)-thiazol-2-yl]-naphthalen-1-yl-amine 
• 81979-39-7 [3-Methylsulfanyl-1-(3-naphthalen-1-yl-thioureido)-propyl]-phosphonic acid diphenyl ester 
• 82844-31-3 5,5-Bis-(2-hydroxy-phenyl)-3-naphthalen-1-yl-2-thioxo-imidazolidin-4-one 
• 1619-51-8 [4-(4-tert-butyl-phenyl)-thiazol-2-yl]-naphthalen-1-yl-amine 
• 84038-92-6 2-Phenyl-4-oxo-naphtho<1,2-d>thiazolo<3,2-a>pyrimidin 
• 63512-54-9 1-aminonaphthalene-2-thiol 
• 139331-56-9 3-{3-[4-(4-Fluoro-phenyl)-piperazin-1-yl]-propyl}-1H-naphtho[2,1-b][1,4]thiazin-2-one 
• 124646-94-2 N-Cyano-N'-(4'-dimethylaminophenyl)-1,4-naphthoquinone di-imine 
• 124646-92-0 N-Cyano-N'-(4'-diethylamino-2'-methylphenyl)-1,4-naphthoquinone di-imine 
• 124646-96-4 N-Cyano-N'-(4'-diethylamino-2',6'-dimethylphenyl)-1,4-naphthoquinone di-imine 

Relevant academic research and scientific papers

Solid phase deracemization of an atropisomer

The scope of Viedma ripening and temperature cycling with respect to chiral molecules has remained mostlylimited to molecules with a single stereogenic center, while racemization proceeds through inversion at that particularstereocenter. In this article we demonstrate for the first time that atropisomers, chiral rotamers that possess an axis of chirality, can be successfully deracemized in the solid phase by either applying temperature cycling or Viedma ripening.

Green and efficient synthesis of thioureas, ureas, primary: O -thiocarbamates, and carbamates in deep eutectic solvent/catalyst systems using thiourea and urea

An efficient and general catalysis process was developed for the direct preparation of various primary O-thiocarbamates/carbamates as well as monosubstituted thioureas/ureas by using thiourea/urea as biocompatible thiocarbonyl (carbonyl) sources. This procedure used choline chloride/tin(ii) chloride [ChCl][SnCl2]2 with a dual role as a green catalyst and reaction medium to afford the desired products in moderate to excellent yields. Moreover, the DES can be easily recovered and reused for seven cycles with no significant loss in its activity. Besides, the method shows very good performance for synthesizing the desired products on a large scale.

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.

High-performance liquid chromatographic enantioseparation of N-aryl-thioureidoalkylphosphonates and thiourylenedi(alkylphosphonates) on polysaccharide-based chiral stationary phases

The first successful enantioseparation of representative O,O-diphenyl-N-arylthioureidoalkylphosphonates, (±)-Ptc-ValP(OPh)2 & (±)-Ptc-LeuP(OPh)2 and thiourylenedi(isobutyl phosphonate), Tcm[ValP(OPh)2]2 on analytical and semipreparative scale was achieved by high-performance liquid chromatography using polysaccharide-based chiral stationary phases (CPs). Atc-AAP(OPh)2 was obtained using modified tricomponent condensations of the corresponding aldehydes, N-arylthiourea and triphenyl phosphite whereas Tcm[ValP(OPh)2]2 by the condensations of aldehydes, thiourea, and triphenyl phosphite. The prepared, racemic (±)-Atc-AAP(OPh)2 [(±)-Ptc-ValP(OPh)2, (±)-Ptc-LeuP(OPh)2, (±)-Ptc-PglyP(OPh)2 and (±)-Ntc-PglyP(OPh)2] and racemic (±)-Tcm[AAP(OPh)2]2 [(±)-Tcm[NvaP(OPh)2]2 & (±)-Tcm[ValP(OPh)2]2] were adequately characterized and used for chromatographic separations on high-performance liquid chromatography–chiral stationary phases. The best results were obtained for (±)-Ptc-ValP(OPh)2, (±)-Ptc-LeuP(OPh)2 and (±)-Tcm[ValP(OPh)2]2.

Thiocarbonyl Surrogate via Combination of Sulfur and Chloroform for Thiocarbamide and Oxazolidinethione Construction

An efficient and practical thiocarbonyl surrogate via combination of sulfur and chloroform has been developed. A variety of thiocarbamides and oxazolidinethiones have been established, including chiral thiourea catalysts and chiral oxazolidinethione auxiliaries with high selectivity. Meanwhile, pesticides Diafenthiuron (an acaricide), ANTU (a rodenticide), and Chloromethiuron (an insecticide) were practically synthesized through this method in gram scale. Dicholorocarbene, as the key intermediate, was further confirmed via a carbene-trapping control experiment.

HINDERED DISULFIDE DRUG CONJUGATES

The invention relates generally to disulfide drug conjugates wherein a linker comprising a sulfur-bearing carbon atom substituted with at least one hydrocarbyl or substituted hydrocarbyl is conjugated by a disulfide bond to a cysteine sulfur atom of a targeting carrier, and wherein the linker is further conjugated to a drug moiety. The invention further relates to activated linker-drug conjugates suitable for conjugation to a targeting carrier by a disulfide bond. The invention further relates to methods for preparing hindered disulfide drug conjugates.

Synthesis of monosubstituted thioureas by vapour digestion and mechanochemical amination of thiocarbamoyl benzotriazoles

Thiocarbamoyl benzotriazoles, as safe and easy-to-handle isothiocyanate equivalents, were quantitatively converted to N-monosubstituted thioureas by vapour digestion synthesis under an ammonia atmosphere. This simple, but timely process provided a synthetic platform that enabled the "slow" amination reaction to be successfully transformed into a rapid one aided by mechanochemical milling. The ammonium chloride/sodium carbonate equimolar mixture allowed in situ formation of ammonia under ball-milling conditions. This novel and green approach yielded aromatic and aliphatic primary thioureas in near-quantitative isolated yields with workup entirely based on using only water. In addition, the molecular and crystal structures of selected polyaromatic primary thioureas were determined from the synchrotron powder diffraction data.

Synthesis and antitumor evaluation of 5-(benzo[: D] [1,3]dioxol-5-ylmethyl)-4-(tert -butyl)- N -arylthiazol-2-amines

A series of novel N-aryl-5-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(tert-butyl)thiazol-2-amines (C1-C31) were synthesized and evaluated for their antitumor activities against HeLa, A549 and MCF-7 cell lines. Some tested compounds showed potent growth inhibition properties with IC50 values generally below 5 μM against the three human cancer cells lines. Compound C27 showed potent activities against HeLa and A549 cell lines with IC50 values of 2.07 ± 0.88 μM and 3.52 ± 0.49 μM, respectively. Compound C7 (IC50 = 2.06 ± 0.09 μM) was the most active compound against A549 cell line, while compound C16 (IC50 = 2.55 ± 0.34 μM) showed the best inhibitory activity against the MCF-7 cell line. The preliminary mechanism of the inhibitory effect was investigated via further experiments, such as morphological analysis by dual AO/EB staining and Hoechst 33342 staining, and cell apoptosis and cycle assessment by FACS analysis. The results illustrated that compound C27 could induce apoptosis and cause both S-phase and G2/M-phase arrests in HeLa cell line. Therefore, compound C27 could be developed as a potential antitumor agent.

Linker Immolation Determines Cell Killing Activity of Disulfide-Linked Pyrrolobenzodiazepine Antibody-Drug Conjugates

Disulfide bonds could be valuable linkers for a variety of therapeutic applications requiring tunable cleavage between two parts of a molecule (e.g., antibody-drug conjugates). The in vitro linker immolation of β-mercaptoethyl-carbamate disulfides and DNA alkylation properties of associated payloads were investigated to understand the determinant of cell killing potency of anti-CD22 linked pyrrolobenzodiazepine (PBD-dimer) conjugates. Efficient immolation and release of a PBD-dimer with strong DNA alkylation properties were observed following disulfide cleavage of methyl- and cyclobutyl-substituted disulfide linkers. However, the analogous cyclopropyl-containing linker did not immolate, and the associated thiol-containing product was a poor DNA alkylator. As predicted from these in vitro assessments, the related anti-CD22 ADCs showed different target-dependent cell killing activities in WSU-DLCL2 and BJAB cell lines. These results demonstrate how the in vitro immolation models can be used to help design efficacious ADCs.

Synthesis and Cytotoxicity in Vitro of N-Aryl-4-(Tert-butyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine

A series of novel N-aryl-4-(tert-butyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amines were synthesized in a green way. H2O2-NaBr Brominating circulatory system was used in the synthesis of the key intermediate in a mild condition. All of the target compounds were confirmed by1H NMR and elemental analysis and tested for their cytotoxicity against two different human cancer cell lines. The cytotoxicity assay revealed that some of the title compounds showed moderate to strong cytotoxic activities. Compound 2i was the most potent compound with the IC50 values of 9 μMagainst Hela cells and 15 μMagainst Bel-7402 cells, respectively.