148-79-8

Basic information

• Product Name: Thiabendazole
• Synonyms: STORITE;TBZ;TBZ(R);TECTO;TECTO(R);THIBENZOLE(R);THIABENDAZOLE (TM);THIABENDAZOL
• CAS NO: 148-79-8
• Molecular Formula: C₁₀H₇N₃S
• Molecular Weight: 201.25
• EINECS: 205-725-8
• Product Categories: Xanthones;Heterocyclic Compounds;FUNGICIDE;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;API's;API;COUMADIN;agrochemical
• Mol File: 148-79-8.mol
• Article Data: 33

Chemical Properties

• Melting Point: 298-301°C
• Boiling Point: 446 °C at 760 mmHg
• Flash Point: 226.2 °C
• Appearance: light yellow/powder
• Density: 1.2271 (rough estimate)
• Vapor Pressure: 3.89E-06mmHg at 25°C
• Refractive Index: 1.5500 (estimate)
• Storage Temp.: 0-6°C
• Solubility: Soluble in methanol and dimethyl sulfoxide.
• PKA: pKa 4.7 (Uncertain)
• Water Solubility: 0.005 g/100 mL
• Merck: 14,9289
• BRN: 611403
• CAS DataBase Reference: Thiabendazole(CAS DataBase Reference)
• NIST Chemistry Reference: Thiabendazole(148-79-8)
• EPA Substance Registry System: Thiabendazole(148-79-8)

Safety Data

• Hazard Codes: N,Xi
• Statements: 50/53-36/37/38
• Safety Statements: 60-61-36-26
• RIDADR: UN 3077 9/PG 3
• WGK Germany: 2
• RTECS: DE0700000
• TSCA: Yes
• HazardClass: 9
• PackingGroup: III
• Hazardous Substances Data: 148-79-8(Hazardous Substances Data)

Usage

Physical properties

MW 201, pKa not known. Practically insoluble in water.

Pharmacology and mechanism of action

Thiabendazole is a benzimidazole derivative introduced as a veterinary drug during the 1960s and later as a human anthelminthic drug. It has a broad spectrum anthelminthic activity being effective against various types of nematode infections. It is both ovicidal and larvicidal. It is also highly effective against many saprophytic and pathogenic fungi in vitro and has also shown anti-inflammatory, antipyretic and analgesic properties in laboratory animals[1]. Clinically, it is primarily used against Strongyloides stercoralis and cutaneous larva migrans. The mechanism of action is not clearly understood. It has been shown to inhibit the mitochondrial fumurate reductase, which is specific for helminths[2]. Thiabendazole may also affect parasite microtubules, by a mechanism similar to that described for mebendazole (see Mebendazole).

Indications

Thiabendazole is primarily indicated in infections with Strongyloides stercoralis and cutaneous larva migrans. It may also prove useful against Capillaria philippinensis, Trichostrongylus species and alleviate symptoms during the invasion stage of trichinosis.

Interactions

In a single patient, thiabendazole has been reported to have increased the plasma half-life of theophylline by three-fold because of decreased plasma clearance[3].

Side effects

Common side effects include nausea, vomiting, headache, dizziness, and abdominal pain. In one clinical study around 40% of the patients treated experienced side effects including vomiting (25%), headache (11%) and dizziness (11%) [4]. In another study [5], 43 patients treated with the recommended doses of the drug, 34 (89%) suffered side effects. Majorcomplaints included nausea (67%), smelly urine (26%), neuropsychiatric symptoms (23%), malaise (16%), dizziness (16%), anorexia (7%), vomiting (7%), abdominal pain (7%), ‘thought going to die’ (7%), and headache (5%). The patients in the study were largely elderly. Side effects occurred 1–4 hours after drug ingestion and lasted for up to 8–12 hours. Occasionally cholestatic jaundice, skin reactions, crystalluria, diarrhoea, headache, fatigue, drowsiness and drying of mucous membranes may occur. Hyperglycaemia, disturbances in colour vision, bradycardia and hypotension are uncommon. Hypersensitivity reactions such as fever, oedema, and lymphoadenopathy are also rare [4,6]. Single cases of StevensJohnsons syndrome and toxic epidermal necrosis have been reported [6]. The urine of some patients may have an odour much like that observed after eating asparagus; it is attributed to the presence of a metabolite [1,7].

Contraindications and precautions

Thiabendazole should be given with caution to patients with a history of drug hypersensitivity. Dosage reductions must be made in patients with kidney or hepatic failure. Thiabendazole is a potent inhibitor of cytochrome P450, and it is likely to increase the plasma concentrations of drugs metabolized by this route.

Preparations

? Mintesol? (Merck Sharp & Dohme). Oral suspension 100 mg/ml. Tablets 500 mg.

Description

Different sources of media describe the Description of 148-79-8 differently. You can refer to the following data:
1. Thiabendazole is a kind of fungicide and parasiticide. As a fungicide, it can be used for the treatment of mold, blight and many other fungal diseases occurring in fruits and vegetable. As an antiparasitic, it is capable of treating roundworms, hookworms, and other kinds of helminth species that can attack wild animals, livestock and humans. It also has effects of inhibiting the angiogenesis of cells. The mechanism of action is still not fully understood. It has found that Thiabendazole is capable of suppressing the helminth-specific mitochondrial enzyme fumarate reductase, further inhibiting the citric acid cycle, mitochondrial respiration and ATP production, leading to helminth’s death. It may also inhibit the microtubule polymerization processes.
2. Thiabendazole is a broad-spectrum anthelmintic that is active against a variety of helminths. In sheep, thiabendazole (50 mg/kg) kills greater than 95% of adult worms from ten genera, including Trichostrongylus, Cooperia, Nematodirus, Ostertagia, Haemonchus, Oesophagostomum, Bunostomum, Strongyloides, Chabertia, and Trichuris. It also inhibits production of eggs and disrupts larval development. Thiabendazole inhibits fumarate reductase in helminths, which inhibits succinate formation, and therefore energy production through the citric acid cycle. It also inhibits methionine aminopeptidase in E. coli (Ki = 40 nM; IC50 = 47.2 nM). Formulations containing thiabendazole have been used in the control of parasitic infections in livestock.
3. Thiabendazole is also a broad-spectrum systemic fungicide against many fungal pathogens, although this compound was originally introduced as an anthelminthic (25).

References

1. Robinson HJ, Phases HF, Graessle DE (1969). Thiabendazole: lexicological, pharmacological and antifungal properties. Texas Rep Biol Med, 27, 537–560. 2. Sheth UK (1975). Thiabendazole inhibited the fumarate reductase metabolism of helminths. Prog Drug Res, 19, 147. 3. Schneider D, GannonR, Sweeney K, Shore E (1990). Theophylline and antiparasitic drug interactions. A case report and study of the influence of thiabendazole and mebendazole on theophylline pharmacokinetics in adults. Chest, 97, 84–87. 4. Farahmandian I, Arfaa F, Jalali H, Reza M (1977). Comparative studies on the evaluation of the effect of new anthelminthics on various intestinal helminthiasis in Iran. Chemotherapy, 23, 98. 5. Grove DI (1982). Treatment of strongyloidiasis with thiabendazole: an analysis of toxicity and effectiveness. Trans R Soc Trop Med Hyg, 76, 114–118. 6. Robinson HM, Samorodin CS (1976). Thiabendazole-induced toxic epidermal necrolysis. Arch Dermatol, 112, 1757–1760. 7. Robinson HJ, Phases HF, Graessle DE (1978). The lexicological and antifungal properties of thiabendazole. Ecotoxicol Environ Safety, 1, 471–476.

Chemical Properties

Light yellow powder

Originator

Mintezol,MSD,US,1967

Uses

Different sources of media describe the Uses of 148-79-8 differently. You can refer to the following data:
1. A drug used in the treatment of helminthiases
2. anticoagulant, rodenticide
3. Thiabendazole is widely used as a post-harvest systemic fungicide on citrus and bananas. It is active against fruit rots in bananas, citrus, apples and pears; bulb and corm rots in ornamentals; storage rots in sweet potato and potato and is also used to control Dutch elm disease. It is the original benzimidazole anthelmintic for both human and animal health usages.
4. Systemic fungicide used for diseases of fruits and vegetables and for control of Dutch elm disease.

Definition

ChEBI: A member of the class of benzimidazoles carrying a 1,3-thiazol-4-yl substituent at position 2. A mainly post-harvest fungicide used to control a wide range of diseases including Aspergillus, Botrytis, Cladosporium and Fusarium.

Manufacturing Process

6.5 grams of thiazole-4-carboxylic acid is stirred with 5.9 grams of thionyl chloride in 20 ml xylene for 10 hours at room temperature to form 4-thiazolyl acid chloride. 1.3 grams of 4-thiazolyl acid chloride and 1.3 grams of onitroaniline are then stirred together in 3.5 ml of pyridine at room temperature for about 12 hours. At the end of this time, the mixture is quenched in ice water and the solid nitroanilide recovered by filtration and washed with dilute sodium carbonate solution. The solid is suspended in 15 ml of glacial acetic acid, and 8 ml of 6 N hydrochloric acid added to the suspension. 6 grams of zinc dust is added in small portions to the acetic mixture. After the zinc addition is complete, and the reaction is essentially finished (by visual observation), the reaction mixture is filtered and the filtrate neutralized with concentrated ammonium hydroxide to precipitate 2-(4'- thiazolyl)-benzimidazole. The product is purified by recrystallization from ethyl acetate, according to US Patent 3,274,207.

Therapeutic Function

Anthelmintic

Synthesis Reference(s)

The Journal of Organic Chemistry, 30, p. 259, 1965 DOI: 10.1021/jo01012a061

General Description

White or cream-colored odorless, tasteless powder. Sublimes above 590°F. Fluoresces in acidic solution. Formulated as a dust, flowable powder or wettable powder for use as a systemic fungicide and anthelmintic.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

Thiabendazole is incompatible with a number of pesticides, including copper-containing fungicides, and with highly alkaline materials. Thiabendazole is a chelating agent, binding many metals including iron, but not calcium

Fire Hazard

Flash point data for Thiabendazole are not available; however, Thiabendazole is probably combustible.

Agricultural Uses

Fungicide: Thiabendazole is a fungicide used to control blight, mold, stain and rot that are found on fruit and vegetables; Dutch elm disease; and diseases found in food storage and other diseases. It is also used to treat roundworms and similar conditions in livestock and humans. Registered for use in EU countries. A U.S. EPA restricted use Pesticide (RUP). U.S. Maximum Allowable Residue Levels for Thiabendazole and its metabolite benzimidazole (free and conjugated) in or on the following food commodities:[40CFR 180.242(a) (1)]: apple, wet pomace 12.0 ppm; Avocado (There are no U.S. registrations on the indicated commodity) 10.0 ppm; banana, post harvest 3.0 ppm; bean, dry, seed 0.1 ppm; beet, sugar, dried pulp 3.5 ppm; beet, sugar, roots 0.25 ppm; beet, sugar, tops 10.0 ppm; cantaloupe (There are no U.S. registrations on the indicated commodity) 15.0 ppm; carrot, roots, postharvest 10.0 ppm; citrus, oil 15.0 ppm; fruit, citrus, group 10, postharvest 10.0 ppm; fruit, pome, group 11, postharvest 5.0 ppm; mango 10.0 ppm; mushroom 40.0 ppm; papaya, postharvest 5.0 ppm; potato, postharvest 10.0 ppm; soybean 0.1 ppm; strawberry (There are no U.S. registrations on the indicated commodity) 5.0 ppm; sweet potato (postharvest to sweet potato intended only for use as seed) 0.05 ppm; wheat, grain 1.0 ppm; wheat, straw 1.0 ppm. [40CFR 180.242(a)(2)]: cattle, meat 0.1 ppm; cattle, meat byproducts 0.4 ppm; goat, meat byproducts 0.4 ppm; Hog, meat byproducts 0.3 ppm; horse, meat byproducts 0.4 ppm; milk 0.1 ppm; sheep, meat byproducts 0.4 ppm. [40CFR 180.2010]: Use/Limits: As a seed treatment for dry pea (including field pea, pigeon pea, chickpea or lentil), using a maximum application rate of 0.075 pounds of active ingredient per 100 pounds of seed. Vines or hay grown from treated seed may not be fed to livestock.

Pharmaceutical Applications

Thiabendazole; a thiazolyl benzimidazole available for oral administration. It is active against most common intestinal nematodes. As a result of its larvicidal and ovicidal activity, it is effective in strongyloidiasis, trichinosis, visceral larva migrans and cutaneous larva migrans. It is well absorbed from the small intestine. Peak plasma levels are reached about 1–2 h after a single oral dose of the suspension. It is extensively metabolized in the liver to the 5-hydroxy derivative, which is inactive. Most of the drug is excreted within 24 h. About 90% is excreted in the urine, chiefly as glucuronide or sulfate conjugates; the remainder is passed in the feces. A wide range of unpleasant side effects occur, including nausea and other gastrointestinal upsets, fever and neurological effects. It has been largely replaced by the less toxic benzimidazole carbamates. Although active against Ascaris lumbricoides, E. vermicularis and hookworms, it should not be used as primary therapy for these infections.

Trade name

AGROSOL? AGROSOL?T, (with thiram); APL-LUSTER? ARBOTECT? BOVIZOLE? BRODEX? CHEM-TEK? CITRUS LUSTR? DECCO SALT NO.19? E-Z-EX? EPROFIL? EQUIVET TZ? EQUIZOLE? FRESHGARD? FUNGICIDE 4 T? GRANOX? IRGAGUARD? LOMBRISTOP? MERTEC? MERTECT 160? METASOL TK-100? MINTEZOL? MINZOLUM? MK-360? MYCOZOL? NEMAPAN? NSC 525040? OMNIZOLE? POLIVAL? RIVAL? (captan + PCNB + thiabendazole); RPH? RTU-VITAVAX-EXTRA? STA-FRESH? TBZ 6? TECTO? TECTO RPH? TECTO 10P? TECTO 40 F? TESTO? THIABEN? THIABENDAZOLUM? THIABENZAZOLE? THIABENZOLE? THIBENZOL? THIBENZOLE? THIBENZOLE 200? THIBENZOLE ATT? TIABENDAZOLE? TOBAZ? TOP FORM WORMER? VITAVAX?Thiabendazole Chemical class: Benzimidazole

Contact allergens

This fungicide and vermifuge agent is widely used in agriculture (for example, forcitrus fruits), and in medical and veterinary practice as an anthelmintic drug.

Mechanism of action

Thiabendazole is an antihelmintic drug with a broad spectrum of action. Although the details of its mechanism of action are not conclusively known, it seems likely that its action is mediated by the inhibition of a specific enzyme of helminthes—fumarate reductase. Thiabendazole is active with respect to most nematode infections, including Angyostrongylus cantonesis, Strongyloides stercoralis, Trichinella spiralis, Toxocara canis, Toxocara cati, Ancylostoma caninum, A. braziliense
, A. duodenale, Dracunculus medinesis, Capillaria philippinesis, as well as for treating Acaris cantonesis and Shistosoma stercoralis. Synonyms of this drug are mintezol, minzolum, and others.

Clinical Use

2-(4-Thiazolyl)benzimidazole (Mintezol) occurs as a whitecrystalline substance that is only slightly soluble in waterbut is soluble in strong mineral acids. Thiabendazole is abasic compound with a pKa of 4.7 that forms complexeswith metal ions.Thiabendazole inhibits the helminth-specific enzymefumarate reductase. It is not known whether metal ionsare involved or if the inhibition of the enzyme is related tothiabendazole’s anthelmintic effect. Benzimidazole anthelminticdrugs such as thiabendazole and mebendazolealso arrest nematode cell division in metaphase by interferingwith microtubule assembly. They exhibit a highaffinity for tubulin, the precursor protein for microtubulesynthesis.Thiabendazole has broad-spectrum anthelmintic activity.It is used to treat enterobiasis, strongyloidiasis (threadworminfection), ascariasis, uncinariasis (hookworm infection), andtrichuriasis (whipworm infection). It has also been used torelieve symptoms associated with cutaneous larva migrans(creeping eruption) and the invasive phase of trichinosis. Inaddition to its use in human medicine, thiabendazole iswidely used in veterinary practice to control intestinalhelminths in livestock.

Safety Profile

Moderately toxic by ingestion. An experimental teratogen. A questionable carcinogen. Experimental reproductive effects. Mutation data reported. When heated to decomposition it emits toxic fumes of SOX and NOX. See also SULFIDES.

Synthesis

Thiabendazole, 2-(4
-thiazolyl)benzimidazole (38.1.9), is also made in the same manner—heterocyclization which occurs upon reacting o-phenylendiamine with 1,3-thiazol-4-carboxylic acid.

Veterinary Drugs and Treatments

Thiabendazole has been used for the removal of the following parasites in dogs: ascarids (Toxocara canis, T. leonina), Strongyloides stercoralis, and Filaroides. It has been used systemically as an anti-fungal agent in the treatment of nasal aspergillosis and penicillinosis. Topical and otic use of thiabendazole for the treatment of various fungi is also commonly employed. Thiabendazole is indicated (labeled) for the removal of the following parasites in cattle: Haemonchus spp., Ostertagia spp., Trichostrongylus spp., Nematodirus spp., Cooperia spp. and Oesophagostomum radiatum. Thiabendazole is indicated (labeled) for the removal of the following parasites in sheep and goats: Haemonchus spp., Ostertagia spp., Trichostrongylus spp., Nematodirus spp., Cooperia spp., Chabertia spp., Bunostomum spp. and Oesophagostomum spp. Thiabendazole is indicated (labeled) for the removal of the following parasites in horses: Strongylus spp., craterstomum spp., Oesphagodontus spp., Posteriostomum spp., Cyathostomum spp., Cylicocylus spp., Cylicostephanus spp., Oxyuris spp., and Parasacaris spp. Thiabendazole is indicated (labeled) for the removal or prevention of the following parasites in swine: large roundworms (Ascaris suum) (prevention), and in baby pigs infested with Strongyloides ransomi. Although not approved, thiabendazole has been used in pet birds and llamas. See the Dosage section for more information. In many geographic areas, significant thiabendazole resistance problems have developed and, for many parasites, other anthelmintics would be a better choice for treatment. When used topically, thiabendazole has antidermatophytic properties.

Environmental Fate

Thiabendazole does not hydrolyze readily, nor it is metabolized in soil under aerobic or anaerobic conditions. While it photodecomposes in minutes in aqueous solutions, photodecomposition of thiabendazole in soil did not cause more than 40% reduction. Thiabendazole is also only slightly water soluble, and does not migrate in soil. Thus, it is unlikely to contaminate groundwater. If released into the atmosphere, it exists primarily in the particulate phase. In the vapor phase, it will degrade in the atmosphere by reacting with photochemically produced hydroxyl radicals with an estimated half-life of 6 h.

Metabolic pathway

The primary photolytic degradation of thiabendazole involves the cleavage of the thiazole-benzimidazole ring linkage. In animals, thiabendazole is extensively oxidised in bluegill sunfish, hens, goats, sheep, cattle, mice, rats and humans, followed by conjugation. When foliarly applied to plants, degradation to benzimidazole and its conjugates occurred. Benzimidazole formed in plants is mainly due to photolytic action. The primary degradation/metabolic pathways of thiabendazole in water, soil, plants and animals are depicted in Scheme 1.

Degradation

Thiabendazole (1) is quite stable in aqueous suspension and in acidic media, and it is stable to heat (PM). Opening and/or the cleavage of the thiazole-benzimidazole ring linkage appeared to be the primary photolytic degradation pathway. Thiabendazole was photolysed to (benzimidazol-2-yl)carboxamide (2) and benzimidazole (3) under natural sunlight exposure on sugar beet leaf surfaces or on glass plates (Jacob et al., 1975). Thiabendazole was also photolysed in aqueous solution when exposed to a Pyrex glass filtered high pressure mercury lamp (≥290 nm). In addition to 2 and 3, photoproducts included degradates 4-8 (Murthy et al., 1996). Compound 2 was proposed to result from hydrolysis of (benzimidazol-2-yl)nitrile (7). The rate constant for photolysis was not affected sigruficantly by the presence of either fulvic or humic acids, indicating that indirect photolysis does not play a large role in the degradation of thiabendazole.

InChI:InChI=1/C10H6N2S2/c1-2-4-9-7(3-1)12-10(14-9)8-5-13-6-11-8/h1-6H

Synthetic route

C10H9N3S*ClH → thiabendazole (148-79-8)

Conditions	Yield
With sodium hypochlorite; sodium carbonate In methanol; water at 0 - 65℃; for 1.5h; pH=9 - 10;	97.82%
Stage #1: C10H9N3S*ClH With sodium carbonate In methanol; water at 0 - 5℃; for 0.333333h; Stage #2: With sodium hypochlorite In methanol; water at 5 - 65℃; for 2h;

thiazole-4-carbonitrile (1452-15-9) + 1,2-diamino-benzene (95-54-5) + ascorbic acid (50-81-7) → thiabendazole (148-79-8)

Conditions	Yield
With hydrogenchloride; ethylenediaminetetraacetic acid In water	92.7%

thiazole-4-carbonitrile (1452-15-9) + o-phenylenediamine hydrochloride (39145-59-0) + 1,2-diamino-benzene (95-54-5) + ascorbic acid (50-81-7) → thiabendazole (148-79-8)

Conditions	Yield
With hydrogenchloride; ethylenediaminetetraacetic acid In methanol; water	91.7%
With hydrogenchloride; ethylenediaminetetraacetic acid In water

Thiazole-4-carboxylic acid (3973-08-8) + 1,2-diamino-benzene (95-54-5) → thiabendazole (148-79-8)

Conditions	Yield
Stage #1: 1,2-diamino-benzene With polyphosphoric acid at 150℃; Inert atmosphere; Stage #2: Thiazole-4-carboxylic acid at 230℃; for 2h; Reagent/catalyst; Temperature; Inert atmosphere;	88%
With polyphosphoric acid for 3h; Reflux;

thiazole-4-carbonitrile (1452-15-9) + 1,2-diamino-benzene (95-54-5) + ascorbic acid (50-81-7) + butan-1-ol (71-36-3) → thiabendazole (148-79-8)

Conditions	Yield
With methanesulfonic acid In water	87.1%
With acetic acid In water	75.4%

1,3-thiazole-4-carbaldehyde (3364-80-5) + 1,2-diamino-benzene (95-54-5) → thiabendazole (148-79-8)

Conditions	Yield
With sodium metabisulfite In N,N-dimethyl-formamide at 120℃;	85%
Stage #1: 1,3-thiazole-4-carbaldehyde; 1,2-diamino-benzene In N,N-dimethyl-formamide for 0.0833333h; Inert atmosphere; Stage #2: With sodium metabisulfite In N,N-dimethyl-formamide at 20℃; Inert atmosphere;
With sodium disulfite In N,N-dimethyl-formamide at 20℃; for 8h;
With sodium metabisulfite In N,N-dimethyl-formamide at 120℃;
With sodium metabisulfite In N,N-dimethyl-formamide for 6h;

thiazole-4-carbonitrile (1452-15-9) + aminosulfonic acid (5329-14-6) + 1,2-diamino-benzene (95-54-5) + ascorbic acid (50-81-7) + butan-1-ol (71-36-3) → thiabendazole (148-79-8)

Conditions	Yield
In water	75.7%

thiazole-4-carbonitrile (1452-15-9) + tin(II)chloride dihydrate + 1,2-diamino-benzene (95-54-5) + ascorbic acid (50-81-7) + butan-1-ol (71-36-3) → thiabendazole (148-79-8)

Conditions	Yield
In water	74.5%

(E)-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)thiazole-4-carboximidamide → thiabendazole (148-79-8)

Conditions	Yield
With [4,4’-bis(1,1-dimethylethyl)-2,2’-bipyridine-N1,N1‘]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate In tert-butyl methyl ether at 20℃; for 36h; Schlenk technique; Sealed tube; Inert atmosphere;	40%

C18H12F3N3O2S → thiabendazole (148-79-8)

Conditions	Yield
With [4,4’-bis(1,1-dimethylethyl)-2,2’-bipyridine-N1,N1‘]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate In tert-butyl methyl ether at 20℃; for 36h; Schlenk technique; Sealed tube;	40%

MIDA (1H-benzo[d]imidazol-2-yl)boronate + 4-bromo-1,3-thiazole (34259-99-9) → thiabendazole (148-79-8)

Conditions	Yield
With chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); copper diacetate; potassium carbonate In tert-Amyl alcohol; N,N-dimethyl-formamide at 100℃; for 16h; Inert atmosphere;	15%

thiazole-4-carbonitrile (1452-15-9) + 1-butanol+water → thiabendazole (148-79-8)

Conditions	Yield
In water

diisopropyl malonate (13195-64-7) + di-tert-butyl dicarbonate (24424-99-5) + 1,2-dihydroisoquinoline (2859-58-7) → thiabendazole (148-79-8)

Conditions	Yield
In dichloromethane; ethyl acetate

thiocarboxamide (115-08-2) + 2-dibromoacetylbenzimidazole hydrobromide salt → thiabendazole (148-79-8)

Conditions	Yield
With tetraphosphorus decasulfide In ethyl acetate at 45℃; for 2h;

1,2-diamino-benzene (95-54-5) → thiabendazole (148-79-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 3 h / 100 °C 2: sulfuric acid; potassium permanganate / acetone / 1.5 h / 35 - 40 °C 3: bromine; acetic acid / 1 h / 90 °C 4: tetraphosphorus decasulfide / ethyl acetate / 2 h / 45 °C View Scheme
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 0.03 h 2: sulfuric acid; potassium permanganate / acetone 3: acetic acid; bromine 4: tetraphosphorus decasulfide / ethyl acetate / 0.03 h View Scheme
Multi-step reaction with 4 steps 1: hydrogenchloride / water 2: sulfuric acid; potassium permanganate / acetone 3: bromine; acetic acid 4: tetraphosphorus decasulfide / ethyl acetate View Scheme

1-benzimidazol-2-ylethanol (16414-04-3, 19018-24-7) → thiabendazole (148-79-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: sulfuric acid; potassium permanganate / acetone / 1.5 h / 35 - 40 °C 2: bromine; acetic acid / 1 h / 90 °C 3: tetraphosphorus decasulfide / ethyl acetate / 2 h / 45 °C View Scheme
Multi-step reaction with 3 steps 1: sulfuric acid; potassium permanganate / acetone 2: acetic acid; bromine 3: tetraphosphorus decasulfide / ethyl acetate / 0.03 h View Scheme
Multi-step reaction with 3 steps 1: sulfuric acid; potassium permanganate / acetone 2: bromine; acetic acid 3: tetraphosphorus decasulfide / ethyl acetate View Scheme

aniline (62-53-3) → thiabendazole (148-79-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogenchloride / 1,2-dichloro-benzene / 3 h / 135 °C 2.1: sodium carbonate / water; methanol / 0.33 h / 0 - 5 °C 2.2: 2 h / 5 - 65 °C View Scheme

C10H9N3OS → thiabendazole (148-79-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 1 h / 0 °C 2: [4,4’-bis(1,1-dimethylethyl)-2,2’-bipyridine-N1,N1‘]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate / tert-butyl methyl ether / 36 h / 20 °C / Schlenk technique; Sealed tube; Inert atmosphere View Scheme

2-dibromoacetylbenzimidazole hydrobromide salt + formamide (77287-34-4, 77287-35-5, 60100-09-6) → thiabendazole (148-79-8)

Conditions	Yield
With tetraphosphorus decasulfide In ethyl acetate for 0.0333333h;
With tetraphosphorus decasulfide In ethyl acetate

MIDA ((2-((tert-butoxycarbonyl)amino)phenyl)carbamoyl)boronate → thiabendazole (148-79-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: trifluoroacetic acid / dichloromethane 2: chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); copper diacetate; potassium carbonate / N,N-dimethyl-formamide; tert-Amyl alcohol / 16 h / 100 °C / Inert atmosphere View Scheme

thiabendazole (148-79-8) + copper dichloride → (2-(4'-thiazolyl)benzimidazole)-dichloro-copper(II) (16091-87-5)

Conditions	Yield
In ethanol mixing of solns. (molar ratio metal:ligand 1:1), boiling (1-3 h); filtration, washing (EtOH), drying (air); elem. anal.;	98%

thiabendazole (148-79-8) + mercury dichloride → [(2-(4'-thiazolyl)benzimidazole)]mercury dichloride

Conditions	Yield
In ethanol molar ratio Hg : ligand = 1 : 1, stirring, boiling (1 h, pptn.); filtration off, washing (EtOH), drying (in air); elem. anal.;	98%

thiabendazole (148-79-8) + benzoyl halide → 1-benzoyl-2-thiazol-4-yl-1H-benzoimidazole (3916-49-2)

Conditions	Yield
With Amberlite IRA-400 (Cl(1-)form) resin In methanol	96%

2-Fluoro-5-nitropyridine (456-24-6) + thiabendazole (148-79-8) → 4-(1-(5-nitropyridin-2-yl )-1H-benzo[d]imidazol-2-yl)thiazole

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 23℃; for 12h; Inert atmosphere;	95%

thiabendazole (148-79-8) + isopropyl halide → 1-isopropyl-2-thiazol-4-yl-1H-benzoimidazole

Conditions	Yield
With Amberlite IRA-400 (Cl(1-)form) resin In methanol	94%

thiabendazole (148-79-8) + phenyl-acetyl halide → 2-phenyl-1-(2-thiazol-4-yl-benzoimidazol-1-yl)-ethanone

Conditions	Yield
With Amberlite IRA-400 (Cl(1-)form) resin In methanol	94%

thiabendazole (148-79-8) + manganese(ll) chloride → (2-(4'-thiazolyl)benzimidazole)-dichloro-manganese(II) (102412-37-3)

Conditions	Yield
In ethanol mixing of solns. (molar ratio metal:ligand 1:1), boiling (1-3 h); filtration, washing (EtOH), drying (air); elem. anal.;	94%

benzyl bromide (100-39-0) + thiabendazole (148-79-8) → 4-(1-benzyl-1H-benzo[d]imidazol-2-yl)thiazole (33705-43-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃; Inert atmosphere;	94%
With sodium hydride In N,N-dimethyl-formamide at 20℃;	87%
Stage #1: thiabendazole With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: benzyl bromide In N,N-dimethyl-formamide at 20℃; for 4h; Schlenk technique; Inert atmosphere;	65%

bis[dichloro(pentamethylcyclopentadienyl)iridium(III)] (12354-84-6, 12354-85-7) + thiabendazole (148-79-8) → [(η5‑C5Me5)IrCl(κ2‑N,N‑thiabendazole)]Cl

Conditions	Yield
In dichloromethane at 20℃; for 20h; Inert atmosphere; Schlenk technique;	94%

thiabendazole (148-79-8) + allyl halide → 1-allyl-2-thiazol-4-yl-1H-benzoimidazole

Conditions	Yield
With Amberlite IRA-400 (Cl(1-)form) resin In methanol	93%

thiabendazole (148-79-8) + butyl halide → 1-butyl-2-thiazol-4-yl-1H-benzoimidazole

Conditions	Yield
With Amberlite IRA-400 (Cl(1-)form) resin In methanol	93%

thiabendazole (148-79-8) + zinc(II) chloride (7646-85-7) → (2-(4'-thiazolyl)benzimidazole)-dichloro-zinc (16091-86-4)

Conditions	Yield
In ethanol mixing of solns. (molar ratio metal:ligand 1:1), boiling (1-3 h); filtration, washing (EtOH), drying (air); elem. anal.;	93%

thiabendazole (148-79-8) + cinnamyl halide → (E)-3-Phenyl-1-(2-thiazol-4-yl-benzoimidazol-1-yl)-propenone

Conditions	Yield
With Amberlite IRA-400 (Cl(1-)form) resin In methanol	92%

thiabendazole (148-79-8) + ethyl halide → 4-(1-ethyl-1H-benzo[d]imidazol-2-yl)thiazole

Conditions	Yield
With Amberlite IRA-400 (Cl(1-)form) resin In methanol	92%

thiabendazole (148-79-8) + propyl halide → N-propyl-2-(4-thiazolyl)benzimidazole (118625-65-3)

Conditions	Yield
With Amberlite IRA-400 (Cl(1-)form) resin In methanol	92%

thiabendazole (148-79-8) + benzyl halide → 4-(1-benzyl-1H-benzo[d]imidazol-2-yl)thiazole (33705-43-0)

Conditions	Yield
With Amberlite IRA-400 (Cl(1-)form) resin In methanol	91%
With sodium hydride In N,N-dimethyl-formamide at 20℃;

sodium docusate (577-11-7) + thiabendazole (148-79-8) → thiabendazolium docusate (1337932-57-6)

Conditions	Yield
Stage #1: thiabendazole With hydrogenchloride In water at 20℃; for 1h; Stage #2: sodium docusate In water; acetone at 20℃; Product distribution / selectivity;	91%

thiabendazole (148-79-8) + methyl iodide (74-88-4) → 4-(1-methyl-1H-benzo[d]imidazol-2-yl)thiazole (32594-70-0)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20℃;	90%
Stage #1: thiabendazole With sodium hydride In N,N-dimethyl-formamide; benzene for 0.5h; Stage #2: methyl iodide In N,N-dimethyl-formamide; benzene for 1h; Heating;	79%
Stage #1: thiabendazole With caesium carbonate In dimethyl sulfoxide at 80℃; for 1.5h; Inert atmosphere; Schlenk technique; Stage #2: methyl iodide In dimethyl sulfoxide at 20℃; for 20h; Inert atmosphere; Schlenk technique;	71%
With sodium hydride; N,N-dimethyl-formamide In benzene Heating;
With sodium hydride In N,N-dimethyl-formamide

thiabendazole (148-79-8) + acetyl halide → 1-Acetyl-2-<4>thiazolyl-benzimidazole (3916-51-6)

Conditions	Yield
With Amberlite IRA-400 (Cl(1-)form) resin In methanol	90%

thiabendazole (148-79-8) + carboxymethyl halide → (2-Thiazol-4-yl-benzoimidazol-1-yl)-acetic acid

Conditions	Yield
With Amberlite IRA-400 (Cl(1-)form) resin In methanol	90%

thiabendazole (148-79-8) + methyl halide → 4-(1-methyl-1H-benzo[d]imidazol-2-yl)thiazole (32594-70-0)

Conditions	Yield
With Amberlite IRA-400 (Cl(1-)form) resin In methanol	90%
With sodium hydride In N,N-dimethyl-formamide at 20℃;

thiabendazole (148-79-8) + nickel dichloride → (2-(4'-thiazolyl)benzimidazole)2Cl2 nickel(II)

Conditions	Yield
In ethanol mixing of solns. (molar ratio metal:ligand 1:2), boiling (1-3 h); filtration, washing (EtOH), drying (air); elem. anal.;	90%

nickel(II) nitrate hexahydrate + thiabendazole (148-79-8) → [Ni(2-(4'-thiazolyl)benzimidazole)3]Cl2*3.5H2O

Conditions	Yield
In ethanol addn. of a soln. of metal salt in ethanol to a soln. of ligand in ethanol, standing for 1 wk; elem. anal.;	89%

aqueous cadmium chloride + diphenic acid (863305-32-2) + water (7732-18-5) + thiabendazole (148-79-8) → Cd2(dpa)2(btz)2(H2O)2 (1585253-38-8)

Conditions	Yield
Stage #1: aqueous cadmium chloride; diphenic acid; water; thiabendazole With sodium hydroxide In methanol; N,N-dimethyl-formamide for 0.5h; pH=6; Stage #2: In methanol; N,N-dimethyl-formamide at 130℃; for 72h; Sealed tube;	88%

N-(4-nitrophenyl)bromoacetamide (3598-91-2) + thiabendazole (148-79-8) → N-(4-nitrophenyl)-2-(2-(thiazol-4-yl)-1H-benzo[d]imidazol-1-yl)acetamide

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 25℃; for 8h;	88%

thiabendazole (148-79-8) + 1-bromomethyl-3-nitrobenzene (3958-57-4) → 4-(1-(3-nitrobenzyl)-1H-benzo[d]imidazol-2-yl)thiazole

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20℃;	88%

Upstream product

• 13195-64-7 diisopropyl malonate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 2859-58-7 1,2-dihydroisoquinoline 
• 34259-99-9 4-bromo-1,3-thiazole 
• 77287-34-4 formamide 
• 62-53-3 aniline 
• 16414-04-3 1-benzimidazol-2-ylethanol 
• 95-54-5 1,2-diamino-benzene 
• 115-08-2 thiocarboxamide 
• 3973-08-8 Thiazole-4-carboxylic acid 
• 3364-80-5 1,3-thiazole-4-carbaldehyde 
• 1452-15-9 thiazole-4-carbonitrile 
• 50-81-7 ascorbic acid 
• 39145-59-0 o-phenylenediamine hydrochloride 

Downstream Products

• 32594-70-0 4-(1-methyl-1H-benzo[d]imidazol-2-yl)thiazole 
• 5805-52-7 1H-benzo[d]imidazole-2-carboxamide 
• 1865-09-4 ethyl 1H-benzimidazole-2-carboxylate 
• 58575-68-1 1-[2-(5-Phenyl-[1,2,4]oxadiazol-3-yl)-ethyl]-2-thiazol-4-yl-1H-benzoimidazole 
• 62124-67-8 1-(2-benzyloxyethoxycarbonyl)-2-(4-thiazolyl)-benzimidazole 
• 1207456-41-4 C₁₈H₁₂Cl₂N₄OS 
• 1009450-70-7 N-(4-bromophenyl)-2-(2-(thiazol-4-yl)-1H-benzo[d]imidazol-1-yl)acetamide 
• 351355-01-6 N-(4-chlorophenyl)-2-(2-(thiazol-4-yl)-1H-benzo[d]imidazol-1-yl)acetamide 
• 1081112-26-6 2-(thiazol-4-yl)-1-{3-[4-(3-acetamidophenyl)piperidin-1-yl]propyl}-1H-benzimidazole 
• 33705-43-0 4-(1-benzyl-1H-benzo[d]imidazol-2-yl)thiazole 

Related news

Enhanced fluorescence of terbium with Thiabendazole (cas 148-79-8) and application in determining trace amounts of terbium and Thiabendazole (cas 148-79-8)09/29/2019

In this paper, a simple, rapid and sensitive fluorescence method based on the formation of terbium (Tb3+) complex has been developed for the rapid detection of Tb3+ in water. The fluorescence sensor has been studied by using terbium complexed with thiabendazole (TBZ) while acetonitrile (MeCN) as...detailed

Relevant articles and documents

Carboxyboronate: A Versatile C1 Building Block

The synthesis and applications of carboxy-MIDA-boronate, a novel C1 building block, are described. This molecule is accessible via a ruthenium tetraoxide-mediated cleavage of commercially available ethynyl-MIDA-boronate. In the course of this study, carboxy-MIDA-boronate was found to possess ambident reactivity towards nucleophiles. Carboxylic acid derivatization produces a broad range of previously unknown carbamoyl-, oxycarbo- and thiocarboboronates. Carboxy-MIDA-boronate and its derivatives undergo condensations to access borylated heterocycles with boron at positions that are difficult to access using alternate methods. The resulting heterocycles participate in the Suzuki–Miyaura cross-coupling reaction, enabling entry into diverse bis(heteroaryl) motifs. The carbon monoxide-releasing capacity of carboxy-MIDA-boronate was also examined and applied in palladium-catalyzed carbonylation.

-

-

New synthesis method of thiabendazole

The invention relates to a new synthetic route of a drug commonly named as thiabendazole. Thiazole-4-formaldehyde is used as a raw material, and is condensed with hydroxylamine hydrochloride to obtainthiazole-4-formaldoxime, thiazole-4-formaldoxime is subjected to chlorination by using NCS, and then reacts with aniline to obtain N-phenylthiazole-4-methylamine oxime, then N-phenylthiazole-4-methylamine oxime reacts with p-trifluoromethyl benzoyl chloride to obtain an amidoxime ester, and finally a visible-light-catalyzed free radical reaction is adopted for cyclization to obtain thiazole. According to the method, the visible-light-catalyzed free radical reaction is used to the synthesis of thiabendazole for the first time, the reaction conditions of a high temperature and a strong acid inthe traditional synthesis method are avoided, and thereby the reaction is greener and milder. The method has a broad spectrum, and can also be used for synthesis of imidazole compounds Ia-Ial.

Preparation method of thiabendazole technical

The invention provides a preparation method of a thiabendazole technical. Compared with the prior art, in the preparation method, raw materials are equally divided into multiple parts and placed in different containers for preparation, the reaction time interval of the two adjacent reaction containers is 2-4 minutes, data in the reaction is recorded in the interval time, products obtained from thecontainers with the maximum pH value and the minimum pH value are removed, the PH value of a final product is guaranteed, and product quality is ensured.