645-65-8

Basic information

• Product Name: Imidazole-4-acetic acid
• Synonyms: 2-(3H-IMIDAZOL-4-YL)ACETIC ACID;midazole-4-acetic acidI;(1H-Imidazol-4-yl)acetic acid;Imidazole-4-acetic acid;2-(1H-imidazol-5-yl)acetic acid;2-(1H-imidazol-5-yl)ethanoic acid;1H-Imidazol-4-ylacetic acid hydrochloride;2-(1H-IMidazol-5-yl)acetic acid hydrochloride
• CAS NO: 645-65-8
• Molecular Formula: C₅H₆N₂O₂
• Molecular Weight: 126.11
• Product Categories: Imidaxoles
• Mol File: 645-65-8.mol
• Article Data: 3

Chemical Properties

• Melting Point: 217-219 °C (decomp)
• Boiling Point: 447.343 °C at 760 mmHg
• Flash Point: 224.345 °C
• Appearance: /
• Density: 1.426 g/cm³
• Storage Temp.: 2-8°C
• PKA: 3.60±0.10(Predicted)
• CAS DataBase Reference: Imidazole-4-acetic acid(CAS DataBase Reference)
• NIST Chemistry Reference: Imidazole-4-acetic acid(645-65-8)
• EPA Substance Registry System: Imidazole-4-acetic acid(645-65-8)

Safety Data

• Hazardous Substances Data: 645-65-8(Hazardous Substances Data)

Usage

General Description

Imidazole-4-acetic acid is a chemical compound with the molecular formula C6H6N2O2. It is a derivative of imidazole and is known for its role as a histidine derivative and as a component of metabolic pathways. Imidazole-4-acetic acid has been studied for its potential pharmaceutical applications, particularly in the treatment of inflammation and autoimmune diseases. It also acts as a precursor in the synthesis of various pharmaceutical compounds, making it a valuable intermediate in organic chemistry. The compound's structure and functional groups make it suitable for a wide range of chemical reactions and applications in both research and industrial settings.

InChI:InChI=1/C5H6N2O2/c8-5(9)1-4-2-6-3-7-4/h2-3H,1H2,(H,6,7)(H,8,9)

Synthetic route

4-cyanomethylimidazole (18502-05-1) → 2-(1H-imidazol-4-yl)acetic acid (645-65-8)

Conditions	Yield
With ethanol; sodium
With sodium hydroxide; water
With hydrogenchloride; water

α-oxy-β--propionic acid → 2-(1H-imidazol-4-yl)acetic acid (645-65-8)

Conditions	Yield
With barium permanganate; sulfuric acid

2-(1H-imidazol-4-yl)ethanol (872-82-2) + water (7732-18-5) → 2-(1H-imidazol-4-yl)acetic acid (645-65-8)

Conditions	Yield
UV-Licht.Irradiation;

urocanic Acid (3465-72-3) → 2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 4(5)formylimidazole (3034-50-2) + imidazole-4-carboxylic acid (1072-84-0) + (Z)-urocanic acid (7699-35-6)

Conditions	Yield
With dihydrogen peroxide pH=7.2; Product distribution / selectivity; aqueous phosphate buffer; UV-irradiation;

urocanic Acid (3465-72-3) → 2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 4(5)formylimidazole (3034-50-2) + imidazole-4-carboxylic acid (1072-84-0)

Conditions	Yield
With dihydrogen peroxide pH=7.2; Product distribution / selectivity; Fenton Oxidation; aqueous phosphate buffer;
With dihydrogen peroxide In water pH=7.2; Product distribution / selectivity; Fenton Oxidation;

methanol (67-56-1) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → (1H-imidazol-4-yl)-acetic acid methyl ester (4200-46-8)

Conditions	Yield
With thionyl chloride for 4h; Reflux;	99%
With hydrogenchloride Heating;
With hydrogenchloride
With thionyl chloride at 70℃;

methanol (67-56-1) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → methyl 2-(1H-imidazol-4-yl)acetate hydrochloride (51718-80-0)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane at 60℃;	98%
With thionyl chloride for 4h; Heating / reflux;

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + (1S,2S)-2,3-dihydro-1'-(((2-amino-7,7-dimethylbicyclo<2.2.1>hept-1-yl)methyl)sulfonyl)spiro(1H-indene-1,4'-piperidine) (142643-14-9) → (1S,2S)-2,3-dihydro-1'-(((7,7-dimethyl-2-((4-imidazolylacetyl)amino)bicyclo<2.2.1>hept-1-yl)methyl)sulfonyl)spiro(1H-indene-1,4'-piperidine)

Conditions	Yield
With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; 1-hydroxybenzotriazol-hydrate; triethylamine In N,N-dimethyl-formamide at 25℃; for 18h;	92%

ethanol (64-17-5) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → (1H-imidazol-4-yl)-acetic acid ethyl ester (28782-45-8)

Conditions	Yield
With sulfuric acid	90%
With acetyl chloride for 5h;

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 2,4-Dinitrofluorobenzene (70-34-8) → [1-(2,4-dinitrophenyl)-1H-imidazol-4-yl]acetic acid (153527-31-2)

Conditions	Yield
With sodium hydrogencarbonate In N,N-dimethyl-formamide	72%

C20H30N2O2 + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → N-(cyclopentylmethyl)-2-(1H-imidazol-4-yl)-N-{1-(4-methylphenyl)-2-oxo-2-[(tetrahydrofuran-2-ylmethyl)amino]ethyl}acetamide

Conditions	Yield
Stage #1: 2-(1H-imidazol-4-yl)acetic acid With 1-chloro-1-(dimethylamino)-2-methyl-1-propene In dichloromethane at 20℃; for 1h; Stage #2: C20H30N2O2 With triethylamine In dichloromethane at 20℃;	70%

(S)-1-(2-aminoacetyl)pyrrolidine-2-carbonitrile 4-methylbenzenesulfonate (1428264-81-6) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → (S)-N-(2-(2-cyanopyrrolidin-1-yl)-2-oxoethyl)-2-(1H-imidazol-4-yl)acetamide (1448440-90-1)

Conditions	Yield
Stage #1: 2-(1H-imidazol-4-yl)acetic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide for 0.25h; Stage #2: (S)-1-(2-aminoacetyl)pyrrolidine-2-carbonitrile 4-methylbenzenesulfonate In N,N-dimethyl-formamide at 20℃;	66%

1,8-diaminooctan (373-44-4) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → N-(8-(2-(1H-imidazol-4-yl)acetamido)octyl)-2-(1H-imidazol-5-yl)acetamide

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 12h;	65%

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 3,5-bis-trifluoromethylbenzylamine (85068-29-7) → C14H11F6N3O

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In water; N,N-dimethyl-formamide	62%

4-cyano-1H-imidazole-2-carboxylic acid (2-cyclohex-1-enyl-4-piperidin-4-yl-phenyl)-amide trifluoroacetic acid salt + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → 4-cyano-1H-imidazole-2-carboxylic acid {2-cyclohex-1-enyl-4-[1-(2-1H-imidazol-4-yl-acetyl)piperidin-4-yl]phenyl}amide trifluoroacetic acid salt

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 25℃; for 10h;	60%

di-tert-butyl dicarbonate (24424-99-5) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → 4-carboxymethyl-imidazole-1-carboxylic acid tert-butyl ester (112856-43-6)

Conditions	Yield
With dmap; triethylamine In tetrahydrofuran; water at 0 - 20℃;	54%

C35H38N4O3 + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → C54H50N6O8

Conditions	Yield
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 6h;	38%

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 6-nitro-1,4-benzoxazine (28226-22-4) → C13H12N4O4 (928118-22-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20 - 25℃;	38%

C43H44N4O5 (702692-02-2) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → C48H48N6O6

Conditions	Yield
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 6h;	38%

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 4-(2-((5-chloro-2-propoxybenzyl)amino)ethyl)-N-(prop-2-yn-1-yl)benzenesulfon-amide → N-(5-chloro-2-propoxybenzyl)-2-(1H-imidazol-4-yl)-N-(4-(N-(prop-2-yn-1-yl)sulfamo-yl)phenethyl)acetamide

Conditions	Yield
Stage #1: 2-(1H-imidazol-4-yl)acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-(2-((5-chloro-2-propoxybenzyl)amino)ethyl)-N-(prop-2-yn-1-yl)benzenesulfon-amide With triethylamine In dichloromethane at 20℃; for 3h; Inert atmosphere;	35%

3-{4-[(3R)-piperidin-3-ylamino]pyrimidin-2-yl}imidazo[1,2-a]pyridine-6-carbonitrile (1313006-17-5) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → 3-(4-{[(3R)-1-(1H-imidazol-4-ylacetyl)piperidin-3-yl]amino}pyrimidin-2-yl)imidazo[1,2-a]pyridine-6-carbonitrile (1313007-40-7)

Conditions	Yield
Stage #1: 2-(1H-imidazol-4-yl)acetic acid With triethylamine; 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 3-{4-[(3R)-piperidin-3-ylamino]pyrimidin-2-yl}imidazo[1,2-a]pyridine-6-carbonitrile In N,N-dimethyl-formamide	32%
Stage #1: 2-(1H-imidazol-4-yl)acetic acid With triethylamine; 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 3-{4-[(3R)-piperidin-3-ylamino]pyrimidin-2-yl}imidazo[1,2-a]pyridine-6-carbonitrile	32%

ethyl 5-amino-3-(4-chlorophenyl)-4-cyanothiophene-2-carboxylate (1322757-73-2) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → ethyl 5-(2-(1H-imidazol-4-yl)acetamido)-3-(4-chlorophenyl)-4-cyanothiophene-2-carboxylate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃; for 120h; Inert atmosphere;	30%

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + (2S,3S)-3-methyl-2-methylaminopentanoic acid benzyl ester → (2S,3S)-2-[(2-1H-imidazol-4-ylacetyl)methylamino]-3-methylpentanoic acid benzyl ester

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h;	27.4%

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + dimethyl sulfate (77-78-1) → zwitterionic zooanemonin (584-91-8)

dimethyl 3-aminophthalate (34529-06-1) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → dimethyl 3-<<2-(4-carboxymethyl)imidazolyl>azo>phthalate (141344-44-7)

Conditions	Yield
With hydrogenchloride; sodium carbonate; sodium nitrite 2.) 4 deg C, 30 min; Multistep reaction;

2-(methoxycarbonyl)-6-aminobenzoic acid (103259-06-9) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → methyl 2-carboxy-3-<<2-(4-carboxymethyl)imidazolyl>azo>benzoate (141344-48-1)

Conditions	Yield
With hydrogenchloride; sodium carbonate; sodium nitrite 2.) 4 deg C, 30 min; Multistep reaction;

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 3-amino-2-(methoxycarbonyl)benzoic acid (113579-20-7) → methyl 2-carboxy-6-<<2-(4-carboxymethyl)imidazolyl>azo>benzoate (141344-43-6)

Conditions	Yield
With hydrogenchloride; sodium carbonate; sodium nitrite 2.) 4 deg C, 30 min; Multistep reaction;

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 3-Amino-N,N-dimethyl-phthalamic acid methyl ester → N,N-dimethyl-2-carbomethoxy-6-<<2-(4-carboxymethyl)imidazolyl>azo>benzamide (141344-46-9)

Conditions	Yield
With hydrogenchloride; sodium carbonate; sodium nitrite 2.) 4 deg C, 30 min; Multistep reaction;

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 2-amino-5-<3,5-bis(trifluoromethyl)phenyl>-1-(3-indolyl)-3-pentanone hydrochloride → N-[(S)-4-(3,5-Bis-trifluoromethyl-phenyl)-1-(1H-indol-3-ylmethyl)-2-oxo-butyl]-2-(1H-imidazol-4-yl)-acetamide

Conditions	Yield
With triethylamine; 1,1'-carbonyldiimidazole 1.) DMF, CH2Cl2, 2.) DMF, CH2Cl2; Multistep reaction;

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + chloroformic acid ethyl ester (541-41-3) → 4-(2-Ethoxycarbonyloxy-2-oxo-ethyl)-imidazole-1-carboxylic acid ethyl ester

Conditions	Yield
With triethylamine In dichloromethane at 0 - 5℃; for 0.25h;

Upstream product

• 3465-72-3 urocanic Acid 
• 18502-05-1 2-(1H-imidazol-5-yl)acetonitrile 
• 872-82-2 2-(1H-imidazol-4-yl)ethanol 
• 7732-18-5 water 
• 18502-05-1 4-cyanomethylimidazole 

Downstream Products

• 51718-80-0 methyl 2-(1H-imidazol-4-yl)acetate hydrochloride 
• 183499-85-6 N-Methyl-N-methoxy-2-(1-triphenylmethyl-1H-imidazol-4-yl)acetamide 
• 28782-45-8 (1H-imidazol-4-yl)-acetic acid ethyl ester 
• 1221877-32-2 (S)-2-(2-(1H-imidazol-5-yl)acetamido)-N-(4-phenoxyphenyl)-5-phenylpentanamide 
• 18502-05-1 4-cyanomethylimidazole 
• 151094-26-7 3-Amino-2-(1-trityl-1H-imidazol-4-yl)-butyric acid methyl ester 

Relevant articles and documents

PHARMACEUTICAL AND COSMETIC COMPOSITIONS COMPRISING UROCANIC ACID DERIVATIVES AS RADICAL SCAVENGERS OR ANTIOXIDANTS

Upon exposure to UVB, the epidermal component trans-urocanic acid is not only photoisomerized into cis-urocanic acid, but will also, at least in part, be photooxidized into urocanic acid oxidation products. We hypothesized that urocanic acid oxidation products can mimic UV-induced systemic immunosuppression comparable to the suppressive properties already established for cis-urocanic acid. A crude mixture of urocanic acid oxidation products showed a significant suppression of the sensitization phase of the systemic contact hypersensitivity response to picryl chloride. Three of the urocanic acid oxidation products were selected for this study: imidazole-4-carboxylic acid, imidazole-4-carboxaldehyde and imidazole-4-acetic acid. Effects on the sensitization-, elicitation- and post-elicitation phase of contact hypersensitivity to picryl chloride in BALB/c mice were studied and compared to the effects of cis-urocanic acid. Imidazole-4-carboxaldehyde was equally effective at suppressing the sensitization phase as cis-urocanic acid. The triplet combination of the imidazoles showed more pronounced suppression than that induced by cis-urocanic acid. The most effective compounds for the suppression of the elicitation phase appeared to be imidazole-4-acetic acid and cis-urocanic acid. Significant suppression of the post-elicitation phase was only obtained with the triplet combination of imidazole-4-carboxaldehyde, imidazole-4-carboxylic acid and imidazole-4-acetic acid, which combination appeared to be effective at all three tested phases, Because these three urocanic acid oxidation products are present in UVB-exposed human stratum corneum, these compounds may play a role in UVB-induced immunosuppression.

The oxidation of histamine to imidazoleacetic acid in vivo.

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