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Benzimidazole

HCID 5798
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Basic information

CAS
51-17-2
Standard SMILES
c1ccc2[nH]cnc2c1
InChIKey
HYZJCKYKOHLVJF-UHFFFAOYSA-N
Molecular formula
C7H6N2
Average molar mass
118.14 g/mol
Monoisotopic mass
118.05309819

Overview

Benzimidazole appears as white tabular crystals. (NTP, 1992)

Names & identifiers

Preferred name
Benzimidazole
IUPAC
1H-benzimidazole
English name
Benzimidazole
Molecular formula
C7H6N2
Molecular weight
118.14

Names & synonyms

BENZIMIDAZOLE51-17-21H-BenzimidazoleBenzoimidazole1,3-BenzodiazoleBenziminazole3-Azaindoleo-BenzimidazoleBenzoglyoxalineAzindole1,3-DiazaindeneN,N'-Methenyl-o-phenylenediamine
Show more names
1H-BENZO[D]IMIDAZOLEBenzimidazolBZI1H-BenzoimidazoleTIMTEC-BB SBB004294
NSC 759DTXSID8024573NSC-759E24GX49LD8CHEBI:41275DTXCID704573RefChem:5589CHEBI:36622

Database identifiers

CAS
51-17-2
PubChem CID
5798
DTXSID
DTXSID8024573
ChEMBL
CHEMBL306226
ChEBI
CHEBI:41275
UNII
E24GX49LD8
EC Number
200-081-4
Nikkaji
J2.303E

Properties

Computed structural propertiesFilling in

XLogP
1.3
Topological polar surface area
28.7 Ų
Hydrogen bond donors
1
Hydrogen bond acceptors
1
Rotatable bonds
0
Heavy atoms
9
Formal charge
0
Complexity
103

Experimental & physicochemical properties

DrugsPharmaceuticals -> Listed in ZINC15
pHWeak base
SpringerMaterials PropertiesSchoenflies notation
Pesticides · 2 items

Pesticides -> Fungicides

Environmental transformation -> Pesticide transformation products (metabolite, successor)

LogPlog Kow= 1.32
Color/Form · 3 items

RHOMBIC, BIPYRAMIDAL PLATES IN WATER

Tabular crystals

Othrorombic and monoclinic modifications

Solubility · 4 items

less than 1 mg/mL at 63 °F (NTP, 1992)

Freely soluble in alcohol, sparingly soluble in ether. Practically insoluble in benzene, petroleum ether. One gram dissolves in 2 g boiling xylene. Soluble in aqueous solutions of acids and strong alkalis.

In water, 2.01X10+3 mg/l @ 30 °C

>17.7 [ug/mL] (The mean of the results at pH 7.4)

Boiling Point · 3 items

Safety & regulation

Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.

GHS classification

GHS Classification · 5 items

This chemical does not meet GHS hazard criteria for 3.9% (6 of 153) of reports.

Warning

H302 (92.8%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 153 reports by companies from 5 notifications to the ECHA C&L Inventory.

Hazard information

Regulatory Information · 3 items

Chemical: 1H-Benzimidazole

Status: Active Update: 09-12-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/17477

1H-Benzimidazole: Does not have an individual approval but may be used under an appropriate group standard

Fire HazardsFlash point data for this chemical are not available. It is probably combustible. (NTP, 1992)
Health HazardsACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits highly toxic fumes. (NTP, 1992)
Hazards SummaryMay be an irritant; [MSDSonline]
Reactive GroupAmines, Phosphines, and Pyridines
Reactivity Profile · 1 item

An amine. Neutralizes acids to form salts plus water. These acid-base reactions are exothermic. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated in combination with strong reducing agents, such as hydrides. May be shock sensitive.

Air and Water Reactions

Chemistry & industry

Pharmacology

Mechanism of ActionBenzimidazole prevent tubulin polymerization or spindle movement and their administration can result in aneuploidy.
Metabolism/Metabolites · 3 items

5-HYDROXYBENZIMIDAZOLE IS A MAJOR URINARY METABOLITE OF BENZIMIDAZOLE IN RAT.

SIXTY DAYS AFTER TREATMENT WITH BENZIMIDAZOLE, MELON PLANTS CONTAINED METABOLITES 2-AMINOBENZONITRILE, O-PHENYLENEDIAMINE, ANILINE

Thiabendazole ... Is excreted in the urine as 5-hydroxythiabendazole, conjugated either as the glucuronide or as the sulfate. /Benzimidazoles/

MeSH Pharmacological ClassificationAgents that kill parasitic worms. They are used therapeutically in the treatment of HELMINTHIASIS in man and animal.
Absorption, Distribution and Excretion · 1 item

Benzimidazoles have only limited solubility in water; consequently, minor differences in solubility tend to have a major effect on absorption. Thiabenzole is rapidly absorbed after oral ingestion ... Most of the drug is excreted in the urine ... as 5-hydroxythiabendazole ... . In contrast tablet forms of mebendazole are poorly and erratically absorbed ... And is extensively metabolized. ... Like mebendazole, albendazole is variably and erratically absorbed after oral administration, although its absorbtion may be increased when it is given with a fatty meal.

Uses & manufacturing

Uses · 3 items

The benzimidazoles are a group of systemic fungicides; [HSDB] Classification: agricultural chemical, anthelmintic, anti-infective agent, and experimental pesticide; [ChemIDplus]

Farming (Pesticides) [Category: Industry]

A group of systemic fungicides /Benzimidazoles/

Methods of ManufacturingPrepd by reaction of o-phenylenediamine with formic acid: Wundt, Ber 11, 826 (1878); Wagner, Millett, Org Syn Coll Vol II, 65 (1943).

Related reactions

522 records
New reaction record
HRID 4310 reaction equation
HRID 4310As productuspto-grants-1988_02
HRID 5038 reaction equation
HRID 5038As reactantuspto-grants-1993_09
HRID 7124 reaction equation
HRID 7124As reactantuspto-grants-2006_08
HRID 7126 reaction equation
HRID 7126As reactantuspto-grants-2006_08
HRID 7190 reaction equation
HRID 7190As reactantuspto-grants-2006_08
HRID 16135 reaction equation
HRID 16135As reactantuspto-grants-2010_06
HRID 23311 reaction equation
HRID 23311As reactantuspto-grants-2005_02
HRID 26699 reaction equation
HRID 26699As reactantuspto-grants-1979_04
Page 1 of 66

Compound notes

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greater than 680 °F at 760 mmHg (NTP, 1992)

>360 °C

>360 °C

DecompositionDANGEROUS; WHEN HEATED TO DECOMPOSITION, IT EMITS HIGHLY TOXIC FUMES.
Melting Point · 2 items

338 to 342 °F (NTP, 1992)

170.5 °C

Vapor Pressure0.0000764 [mmHg]
Physical Description · 2 items

Benzimidazole appears as white tabular crystals. (NTP, 1992)

Solid; Soluble in hot water; [Merck Index] Slightly water solubility = 2 g/L at 20 deg C; [ChemIDplus] Off-white or tan powder; [MSDSonline]

Physicochemical properties

Melting point
169 · 169-171 °C (lit.)
Boiling point
360 °C · 360 °C
Density
1.1151 · 1.1151 (rough estimate)
refractive index
1.55 · 1.5500 (estimate)
Flash point
360 °C · 360°C
storage temp.
30 °C · Store below +30°C.
solubility
1 g · xylene: soluble1g in 2g (boiling)(lit.)
form
Crystalline Powder or Crystals
pka
5.532 · 5.532(at 25℃)
color
Beige to brown
Water Solubility
sparingly soluble
λmax
271 nm · 271nm(MeOH)(lit.)
Merck
14 · 14,1081
BRN
109682 · 109682
Henry's Law Constant
2.7 · 2.7×101 mol/(m3Pa) at 25℃, HSDB (2015)
Stability
Stable. Combustible. Incompatible with strong oxidising agents.
InChI
1S/C7H6N2/c1-2-4-7-6(3-1)8-5-9-7/h1-5H,(H,8,9)
InChIKey
HYZJCKYKOHLVJF-UHFFFAOYSA-N
SMILES
c1ccc2[nH]cnc2c1
LogP
1.32 · 1.320
CAS DataBase Reference
51 · 51-17-2(CAS DataBase Reference)
EWG's Food Scores
1 · 1
FDA UNII
24 GX49LD8 · E24GX49LD8
NIST Chemistry Reference
1 H-Benzimidazole · 1H-Benzimidazole(51-17-2)
EPA Substance Registry System
Benzimidazole (51-17-2)
UNSPSC Code
12352100 · 12352100
NACRES
22 · NA.22
Symbol(GHS)
7 · GHS07
Signal word
Warning
Hazard statements
302 · H302
Precautionary statements
264 · P264-P270-P301+P312-P501
PPE
95 · Eyeshields, Gloves, type N95 (US)
Hazard Codes
Xi
Risk Statements
36 · 36/37/38
Safety Statements
37 · 37/39-26-24/25
WGK Germany
3 · 3
RTECS
5425000 · DD5425000
Hazard Note
Irritant
TSCA
TSCA listed
HS Code
29339990 · 29339990
Storage Class
11 · 11 - Combustible Solids
Hazard Classifications
4 Oral · Acute Tox. 4 Oral
Hazardous Substances Data
51 · 51-17-2(Hazardous Substances Data)
Toxicity
50 oral · LD50 oral in mouse: 2910mg/kg
REACH Registrations
Active
Insoluble in water.
Hazard Classes and CategoriesAcute Tox. 4 (92.8%)

Safety & protection

Fire FightingFires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)
First Aid · 1 item

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Nonfire Spill Response · 1 item

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

Disposal Methods · 1 item

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Personal Protective Equipment (PPE) · 1 item

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Toxicology

Environmental Fate · 3 items

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 108(SRC), determined from a structure estimation method(2), indicates that benzimidazole is expected to have high mobility in soil(SRC). Volatilization of benzimidazole from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.7X10-7 atm-cu m/mole, using a fragment constant estimation method(3). Benzimidazole is not expected to volatilize from dry soil surfaces, based upon an estimated vapor pressure of 7.6X10-5 mm Hg(SRC), determined from a fragment constant method(4). There is no information on benzimidazole migration in soil, but benzimidazole-based fungicides Benlate and thiabendazole TBZ did not migrate any appreciable distance in soils(5). These fungicides applied to soil surfaces at 100 ug/g did not move more than 25 mm into the soil(5). Benzimidazole was inhibitory to individual strains of soil bacteria that could degrade benzimidazole-based fungicides(6); furthermore, benzimidazole did not support the growth of mixed cultures of microbes that could grow on benzimidazole-based fungicides(7). In contrast, in soil, repeated applications of benzimidazole led to its enhanced degradation(8). These findings suggest that benzimidazole degradation in soils is cometabolic, and that isolation of the appropriate pure cultures that perform the cometabolism has not yet been achieved(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 110(SRC), determined from an estimation method(2), indicates that benzimidazole is not expected to adsorb to suspended solids and sediment in water(SRC). At low pHs, when benzimidazole (pKa = 5.3(8)) exists in a primarily protonated form, it is expected to adsorb to suspended solids and sediments. Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.7X10-7 atm-cu m/mole(4). According to a classification scheme(5), an estimated BCF of 2.1(SRC), from a log Kow of 1.32(6) suggests the potential for bioconcentration in aquatic organisms is low. Benzimidazole is degraded in soils(7), and therefore biodegradation in water may be an important fate process.

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), benzimidazole, which has an estimated vapor pressure of 7.6X10-5 mm Hg at 25 °C(2), is expected to exist in the both the vapor and particulate phases in the ambient atmosphere. Vapor-phase benzimidazole is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 3.6 hours(SRC), calculated from its rate constant of 3.6X10-11 cu cm/molecule-sec at 25 °C(3). Particulate-phase benzimidazole may be removed from the air by wet and dry deposition(SRC). Benzimidazole absorbs light at 245, 271 and 278 nm, and therefore, has little potential for direct photolysis at environmental wavelengths (>290 nm).

Soil Adsorption/Mobility · 1 item

The Koc of benzimidazole is estimated as 110(SRC), using a log Kow of 1.32(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that benzimidazole is expected to have high mobility in neutral and basic soils. Benzimidazole's pKa of 5.3(4) indicates that it will be in the protonated form in acidic environments, and will tend to adsorb to soil particles and clays.

Artificial Pollution SourcesBenzimidazole's production and use as an intermediate in the synthesis of fungal pesticides(1) may result in its release to the environment through various waste streams.
Environmental Biodegradation · 1 item

AEROBIC: No wastewater degradation data for benzimidazole are available(1). Using several different water and soils as sources of inocula, and using benzimidazole as a sole carbon and energy source, no pure cultures of benzimidazole-degraders were found; furthermore, the compound did not support the growth of any bacteria that grew on benzimidazole-based fungicides(2,3). Pseudomonads and Bacillus species (both of which could degrade benzimidazole-based fungicides) were completely inhibited by benzimidazole at concentrations ranging from 500 to 1000 ug/ml, respectively(2). However, in the aerobic soil environment, benzimidazole (10 ug/g) was completely degraded in 10 days when the soils had been pre-exposed to the compound(4). This suggests that benzimidazole biodegradation is cometabolic, and likely occurs in soils as well as in natural waters.

Environmental Bioconcentration · 1 item

An estimated BCF of 2.1 was calculated for benzimidazole(SRC), using a log Kow of 1.32(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low.

Volatilization from Water/Soil · 1 item

The Henry's Law constant for benzimidazole is estimated as 3.7X10-7 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that benzimidazole is expected to be nonvolatile from water surfaces(2). This Henry's Law constant indicates that benzimidazole is essentially non-volatile(SRC) from moist soils. Benzimidazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 7.6X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(3).

Non-Human Toxicity Excerpts · 5 items

...PHENOXYPROPANEDIOL...CAUSED REVERSIBLE FLACCID PARALYSIS IN ANIMALS. ...SIMILAR EFFECTS /FROM/ BENZIMIDAZOLE.../REPORTED/

BENZIMIDAZOLE DID NOT INDUCE REVERSION RESPONSE IN ESCHERICHIA COLI A 46. SALMONELLA TYPHIMURIUM G 46 DISPLAYED A MUTAGENIC RESPONSE. TRANSITION IN VITRO AS WELL AS IN VIVO.

BENZIMIDAZOLE NON-TOXIC TO LUMBRICUS TERRESTRIS WHEN ADMIN ORALLY.

AT CONCN OF 8.5X10-4 MMOLAR BENZIMIDAZOLE FAILED TO STIMULATE TOBACCO CALLUS GROWTH OR SHOOT FORMATION /IN VITRO/. CONCN OF 0.85 MMOLAR & 1.7 MMOLAR INHIBITED KINETIN-DEPENDENT CALLUS GROWTH, WHEREAS LOWER CONCN HAD NO EFFECT.

For more Non-Human Toxicity Excerpts (Complete) data for BENZIMIDAZOLE (6 total), please visit the HSDB record page.

Environmental Abiotic Degradation · 1 item

The rate constant for the vapor-phase reaction of benzimidazole with photochemically-produced hydroxyl radicals has been estimated as 3.6X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 3.6 hours(SRC) at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Benzimidazole is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(3).

Probable Routes of Human ExposureOccupational exposure to benzimidazole may occur through inhalation and dermal contact with this compound at workplaces where benzimidazole is produced or used. (SRC)
Environmental Fate/Exposure Summary · 1 item

Benzimidazole's production and use as a chemical intermediate in the production of agricultural fungicides may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 7.6X10-5 mm Hg at 25 °C indicates benzimidazole will exist in both vapor and particulate phases in the ambient atmosphere. Vapor-phase benzimidazole will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 3.6 hours. Particulate-phase benzimidazole will be removed from the atmosphere by wet and dry deposition. Benzimidazole has little potential for direct photolysis at environmental wavelengths (>290 nm) since it does not absorb light. If released to soil, benzimidazole is expected to have high mobility based upon an estimated Koc of 110. However, a pKa value of 5.3 at 25 °C suggests that at low pH, the protonated form will exist, and will adsorb to organic carbon and clay more strongly than its neutral counterpart. The un-ionized form of benzimidazole will be unlikely to volatilize from soils based upon an estimated Henry's Law constant of 3.7X10-7 atm-cu m/mole and estimated vapor pressure of 7.6X10-5 mm Hg at 25 °C. Benzimidazole is not readily metabolized by isolated soil microbial strains that metabolize benzimidazole-based fungicides, and is inhibitory to some microbes at concentrations ranging from 500 to 1000 ug/g. Hydrolysis of benzimidazole is not expected to occur due to the lack of hydrolyzable functional groups. If released into water, benzimidazole is not expected to adsorb to suspended solids and sediments, based upon its estimated Koc of 108. However, under acidic conditions, due to a pKa of 5.3, adsorption to suspended solids and sediments may occur. The biodegradation of benzimidazole in aquatic systems has not been demonstrated, but it is degraded in soils, which suggests that it will be degraded in waters as well. Volatilization from water surfaces is not expected to be an important fate process, based upon this compound's estimated Henry's Law constant. An estimated BCF of 2.1 suggests the potential for bioconcentration in aquatic organisms is very low. Occupational exposure to benzimidazole may occur through inhalation and dermal contact with this compound at workplaces where benzimidazole is produced or used. (SRC)

Non-Human Toxicity Values · 3 items

LD50 Rat ip 385 mg/kg

LD50 Mouse oral 2910 mg/kg

LD50 Mouse iv 280 mg/kg

Safety data

PPE
Eyeshields, Gloves, type N95 (US)
wgk
3
tsca
TSCA listed
rtecs
DD5425000
hs_code
29339990
Toxicity
LD50 oral in mouse: 2910mg/kg
risk_code
36/37/38
Signal word
Warning
Symbol(GHS)
GHS07
hazard_code
Xi
hazard_note
Irritant
safety_code
37/39-26-24/25
Storage Class
11 - Combustible Solids
Hazard statements
H302
REACH Registrations
Active
Hazard Classifications
Acute Tox. 4 Oral
Precautionary statements
P264-P270-P301+P312-P501
Hazardous Substances Data
51-17-2(Hazardous Substances Data)
Use ClassificationEnvironmental transformation -> Pesticide transformation products (metabolite, successor)
General Manufacturing Information · 3 items

1H-Benzimidazole: ACTIVE

EFFECTIVE AGENT TO PREVENT TOXIC EFFECT OF AIR POLLUTANTS, SUCH AS OXIDANTS, ON PLANTS.

Not currently registered

Applications · 2 items

UsesBenzimidazole is a building block for making anthelmintic drugs like albendazole, mebendazole and triclabendazole and anti-ulcer drugs like pantoprazole, rabeprazole, lansoprazole and omeprazole. It is used in the preparation of pyrene derived benzimidazole linked polymers (BILPs), which are used for selective carbon dioxide separation applications due to their properties like porous materials, regenerability and sorbent selection parameters.

General DescriptionWhite tabular crystals.

Preparation methods · 1 item

PreparationBenzimidazole is synthesized by cyclizing o-phenylenediamine with formic acid. A mixture of o-phenylenediamine and formic acid is heated in a water bath for 2 hours, then cooled. The pH is adjusted to 10 using 10% sodium hydroxide solution, followed by filtration of the precipitated solid. The solid is washed with cold water to obtain the crude product (yield: 90%). The crude product is then refluxed in water, decolorized with activated carbon, and hot-filtered. Upon cooling the filtrate to room temperature, the purified product is collected by filtration, washed with cold water, and dried at 100°C to obtain the final product.

Upstream & downstream products

Upstream raw materials

o-Phenylenediamine1H-Benzimidazole, 1-(phenylmethyl)-1-tosyl-1H-benzo[d]imidazoleN,N-Diethylformamide2-Aminobenzimidazole

Downstream products

4,5-Imidazoledicarboxylic acid2-AcetylbenzimidazoleThiabendazoleButyl 2-[[3-[[(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)amino]carbonyl]-2-hydroxy-1-naphthyl]azo]benzoatePigment Red 175OxatomideImidazoleOmeprazoleDomperidone5-Bromo-1H-benzimidazole5-NitrobenzimidazoleN-Ethylbenzimidazole1-(4-nitrophenyl)-1H-benzimidazole
Additional notes · 1 item

DefinitionChEBI: 1H-benzimidazole is the 1H-tautomer of benzimidazole. It is a benzimidazole and a polycyclic heteroarene. It is a conjugate acid of a benzimidazolide. It is a tautomer of a 4H-benzimidazole, a 2H-benzimidazole and a 3aH-benzimidazole.