57090-88-7

Basic information

• Product Name: 1H-Imidazole-4-carbonitrile
• Synonyms: 1H-IMIDAZOLE-4-CARBONITRILE;1H-Imidazole-5-carbonitrile;4-Cyano-1H-imidazole;lH-IMidazole-4-carbonitrile
• CAS NO: 57090-88-7
• Molecular Formula: C₄H₃N₃
• Molecular Weight: 93.09
• EINECS: 1312995-182-4
• Product Categories: pharmacetical;Imidazoles & Benzimidazoles
• Mol File: 57090-88-7.mol
• Article Data: 18

Chemical Properties

• Melting Point: 143.5-144.5 °C
• Boiling Point: 388.128 °C at 760 mmHg
• Flash Point: 130.816 °C
• Appearance: /
• Density: 1.29 g/cm³
• Vapor Pressure: 3.13E-06mmHg at 25°C
• Refractive Index: 1.551
• Storage Temp.: 2-8°C
• PKA: 9.17±0.10(Predicted)
• CAS DataBase Reference: 1H-Imidazole-4-carbonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 1H-Imidazole-4-carbonitrile(57090-88-7)
• EPA Substance Registry System: 1H-Imidazole-4-carbonitrile(57090-88-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36
• Safety Statements: 26
• HazardClass: IRRITANT
• Hazardous Substances Data: 57090-88-7(Hazardous Substances Data)

Usage

Uses

1H-Imidazole-4-carbonitrile acts as a reagent in the structure-based optimization of a potent class of arylamide FMS inhibitors.

Synthesis Reference(s)

The Journal of Organic Chemistry, 51, p. 3228, 1986 DOI: 10.1021/jo00366a037Synthesis, p. 677, 2003

InChI:InChI=1/C4H3N3/c5-1-4-2-6-3-7-4/h2-3H,(H,6,7)

Synthetic route

4-(trifluoromethyl)-1H-imidazole (33468-69-8) → 1H-imidazole-4-carbonitrile (57090-88-7)

Conditions	Yield
With ammonium hydroxide at 60℃; for 8h;	87%

4(5)formylimidazole (3034-50-2) → 1H-imidazole-4-carbonitrile (57090-88-7)

Conditions	Yield
Stage #1: 4(5)formylimidazole With pyridine; hydroxylamine hydrochloride at 8 - 30℃; for 2h; Stage #2: With acetic anhydride at 80 - 110℃; for 3.83333h;	82%
With pyridine; hydroxylamine hydrochloride; acetic anhydride at 0 - 110℃; for 5.83333h;	82%
Stage #1: 4(5)formylimidazole With pyridine; hydroxylamine hydrochloride at 8 - 30℃; for 2h; Stage #2: With acetic anhydride at 80 - 110℃; for 0.5h;	82%

1H-imidazole-4-carboxaldehyde oxime (57090-90-1) → 1H-imidazole-4-carbonitrile (57090-88-7)

Conditions	Yield
With acetic anhydride at 20 - 100℃; for 1h;	81%
With acetic anhydride at 78 - 110℃;
Stage #1: 1H-imidazole-4-carboxaldehyde oxime With acetic anhydride at 80 - 110℃; for 3.83333h; Stage #2: With sodium hydroxide In water at 30℃; pH=8; Stage #3: With hydrogenchloride In water pH=2; Product distribution / selectivity;
With pyridine; acetic anhydride at 120℃; for 1.5h;
With acetic anhydride at 80 - 110℃;	42.7 g

4-cyano-5-imidazolecarboxylic acid (56745-98-3) → 1H-imidazole-4-carbonitrile (57090-88-7)

Conditions	Yield
In nitrobenzene for 20h; Heating;	80%

imidazole-4-carboxamide (26832-08-6) → 1H-imidazole-4-carbonitrile (57090-88-7)

Conditions	Yield
Stage #1: imidazole-4-carboxamide With trichlorophosphate In acetonitrile for 15h; Inert atmosphere; Reflux; Stage #2: With sodium hydroxide In water; acetonitrile pH=9 - 11;	65.9%

potassiumhexacyanoferrate(II) trihydrate + 4-bromo-1 H-imidazole (2302-25-2) → 1H-imidazole-4-carbonitrile (57090-88-7)

Conditions	Yield
With t-BuBrettPhos; C44H62NO5PPdS(1-); potassium acetate In 1,4-dioxane; water at 100℃; for 1h; Inert atmosphere; Sealed tube;	34 %Spectr.

n-butyl magnesium bromide (693-03-8) + 1H-imidazole-4-carbonitrile (57090-88-7) → 1-[1H-imidazol-4(5)-yl]pentan-1-one

Conditions	Yield
In tetrahydrofuran at 20℃; Grignard reaction;	96%

1H-imidazole-4-carbonitrile (57090-88-7) + cyclohexylmagnesium bromide (931-50-0) → cyclohexyl[1H-imidazol-4(5)-yl]methanone

Conditions	Yield
In tetrahydrofuran at 20℃; Grignard reaction;	92%

isobutylmagnesium bromide (926-62-5) + 1H-imidazole-4-carbonitrile (57090-88-7) → 1-[1H-imidazol-4(5)-yl]-3-methylbutan-1-one

Conditions	Yield
In tetrahydrofuran at 20℃; Grignard reaction;	90%

1-fluoro-2-methoxy-4-nitrobenzene (454-16-0) + 1H-imidazole-4-carbonitrile (57090-88-7) → 4-cyano-1-(2-methoxy-4-nitrophenyl)-1H-imidazole (1263868-22-9)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 120℃;	89%

1H-imidazole-4-carbonitrile (57090-88-7) + methyl iodide (74-88-4) → 1-methyl-1H-imidazole-4-carbonitrile (66121-69-5)

Conditions	Yield
Stage #1: 1H-imidazole-4-carbonitrile With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 25℃; for 1h; Stage #2: methyl iodide In N,N-dimethyl-formamide; mineral oil at 25℃; for 2h;	86%
With potassium fluoride on basic alumina at 20℃; for 24h;	1.9 g

sec-butylmagnesium bromide (671795-46-3) + 1H-imidazole-4-carbonitrile (57090-88-7) → 1-[1H-imidazol-4(5)-yl]-2-methylbutan-1-one

Conditions	Yield
In tetrahydrofuran at 20℃; Grignard reaction;	85%

n-propylmagnesium bromide (927-77-5) + 1H-imidazole-4-carbonitrile (57090-88-7) → 1-[1H-imidazol-4(5)-yl]butan-1-one

Conditions	Yield
In tetrahydrofuran at 20℃; Grignard reaction;	83%
With sodium hydroxide; sulfuric acid In tetrahydrofuran; hexane; water	83%

1H-imidazole-4-carbonitrile (57090-88-7) + isopropyl bromide (75-26-3) → 1-[1H-imidazol-4(5)-yl]-2-methylpropan-1-one (247174-71-6)

Conditions	Yield
Stage #1: isopropyl bromide With iodine; magnesium In tetrahydrofuran Grignard reaction; Stage #2: 1H-imidazole-4-carbonitrile In tetrahydrofuran at 20℃; for 3h;	82%

di-isopropyl ether (108-20-3) + isopropylmagnesium bromide (920-39-8) + 1H-imidazole-4-carbonitrile (57090-88-7) → 1-[1H-imidazol-4(5)-yl]-2-methylpropan-1-one (247174-71-6)

Conditions	Yield
With sodium hydroxide; sulfuric acid In tetrahydrofuran; water	82%

isopropylmagnesium bromide (920-39-8) + 1H-imidazole-4-carbonitrile (57090-88-7) → 1-[1H-imidazol-4(5)-yl]-2-methylpropan-1-one (247174-71-6)

Conditions	Yield
Stage #1: isopropylmagnesium bromide; 1H-imidazole-4-carbonitrile In tetrahydrofuran at 10℃; for 3.5h; Inert atmosphere; Stage #2: With sulfuric acid In water for 0.5h; Inert atmosphere;	82%

methyl isocyanate (624-83-9) + 1H-imidazole-4-carbonitrile (57090-88-7) → 4-cyano-1-(methylcarbamoyl)imidazole (87864-83-3)

Conditions	Yield
With dibutyltin(II) dilaurate; 2-methyl-1,4-diazabicyclo [2,2,2]octane In dichloromethane for 16h; Ambient temperature;	81%

2,3-dimethylbromobenzene (576-23-8) + 1H-imidazole-4-carbonitrile (57090-88-7) → (2,3-dimethylphenyl)(1H-imidazol-5-yl)methanone

Conditions	Yield
Stage #1: 2,3-dimethylbromobenzene With magnesium; ethylene dibromide In tetrahydrofuran at 40 - 65℃; for 1h; Stage #2: 1H-imidazole-4-carbonitrile With isopropylmagnesium chloride In tetrahydrofuran at -5 - 0℃; for 2h; Stage #3: With sulfuric acid In tetrahydrofuran; water at 30℃; for 3h;	80%

ethylmagnesium bromide (925-90-6) + 1H-imidazole-4-carbonitrile (57090-88-7) → 1-(1H-imidazol-4-yl)-1-propanone

Conditions	Yield
In tetrahydrofuran at 20℃; Grignard reaction;	79%
With sodium hydroxide; sulfuric acid In tetrahydrofuran; hexane; water	63%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + 1H-imidazole-4-carbonitrile (57090-88-7) → 2-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carbonitrile (854044-51-2)

Conditions	Yield
Stage #1: (2-trimethylethylsilylethoxy)methyl chloride; 1H-imidazole-4-carbonitrile With potassium carbonate In acetone at 20℃; for 10h; Stage #2: With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In tetrachloromethane at 60℃; for 4h;	77%
Stage #1: (2-trimethylethylsilylethoxy)methyl chloride; 1H-imidazole-4-carbonitrile With potassium carbonate In acetone at 60℃; Stage #2: With 2,2'-azobis(isobutyronitrile) In tetrachloromethane; acetone
Stage #1: (2-trimethylethylsilylethoxy)methyl chloride; 1H-imidazole-4-carbonitrile With potassium carbonate In acetone at 20℃; for 48h; Inert atmosphere; Stage #2: With N-Bromosuccinimide In tetrahydrofuran at 60℃; Inert atmosphere;	1.24 g
Stage #1: (2-trimethylethylsilylethoxy)methyl chloride; 1H-imidazole-4-carbonitrile With potassium carbonate In acetone at 10 - 20℃; Stage #2: With N-Bromosuccinimide In tetrachloromethane at 60 - 75℃;	800 mg

1H-imidazole-4-carbonitrile (57090-88-7) + N-(diphenylmethylene)-2,2,2-trifluoro-1-ethanamine → C19H13FN4

Conditions	Yield
Stage #1: 1H-imidazole-4-carbonitrile; N-(diphenylmethylene)-2,2,2-trifluoro-1-ethanamine With potassium phosphate In tetrahydrofuran at -78 - 25℃; for 0.5h; Inert atmosphere; Stage #2: With lithium diisopropyl amide In tetrahydrofuran at -78 - 20℃; for 17h; Inert atmosphere; stereoselective reaction;	75%

1H-imidazole-4-carbonitrile (57090-88-7) + methyl iodide (74-88-4) → 1-methyl-1H-imidazole-5-carbonitrile (66121-66-2)

Conditions	Yield
Stage #1: 1H-imidazole-4-carbonitrile With 2,2,6,6-tetramethylpiperidinylmagnesium chloride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at 70℃; for 20h; Inert atmosphere;	74%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + 1H-imidazole-4-carbonitrile (57090-88-7) → 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carbonitrile (854044-50-1)

Conditions	Yield
With potassium carbonate In acetone at 20℃; for 10h;	70%
With potassium carbonate In acetone at 20℃; for 10h; Product distribution / selectivity;	70%
With potassium carbonate In acetone at 20℃; for 10h;	70%

5-fluoro-2-nitrophenol (446-36-6) + 1H-imidazole-4-carbonitrile (57090-88-7) → 1-(3-hydroxy-4-nitrophenyl)-1H-imidazole-4-carbonitrile

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 120℃; for 16h;	68%

phenyl isocyanate (103-71-9) + 1H-imidazole-4-carbonitrile (57090-88-7) → 4-cyano-1-(phenylcarbamoyl)imidazole (87864-82-2)

Conditions	Yield
With dibutyltin(II) dilaurate; 2-methyl-1,4-diazabicyclo [2,2,2]octane In dichloromethane for 16h; Ambient temperature;	60%

ethyl bromoacetate (105-36-2) + 1H-imidazole-4-carbonitrile (57090-88-7) → [4-Cyano-1H-imidazol-1-yl]acetic acid ethyl ester (1154030-58-6)

Conditions	Yield
With sodium ethanolate In ethanol at 20℃; for 16h;	60%
In ethanol; sodium ethanolate

1H-imidazole-4-carbonitrile (57090-88-7) + 2-(trifluoromethyl)pyridine-4-iodide (590371-73-6) → C10H5F3N4

Conditions	Yield
With copper(l) iodide; (R,R)-N,N'-dimethyl-1,2-diaminocyclohexane; caesium carbonate In N,N-dimethyl-formamide at 100℃; for 2h;	59%

2-chloro-3-methoxy-5-nitropyridine (75711-00-1) + 1H-imidazole-4-carbonitrile (57090-88-7) → 1-(3-methoxy-5-nitropyridin-2-yl)-1H-imidazole-4-carbonitrile

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 20 - 50℃; for 16h; Inert atmosphere;	56%
With potassium carbonate In dimethyl sulfoxide at 50℃; for 16h; Inert atmosphere;	56%

1H-imidazole-4-carbonitrile (57090-88-7) + thymidine (50-89-5) → 1-(2-deoxy-β-D-ribofuranosyl)-1H-imidazole-4-carbonitrile + 1-(2-deoxy-β-D-ribofuranosyl)-1H-imidazole-5-carbonitrile

Conditions	Yield
With nucleoside 2-deoxyribosyltransferases class II from L.leichmannii In dimethyl sulfoxide at 50℃; for 2h; pH=6.5; Enzymatic reaction; regioselective reaction;	A 56% B 4%

4-tolyl iodide (624-31-7) + 1H-imidazole-4-carbonitrile (57090-88-7) → 1-(p-tolyl)-1H-imidazole-4-carbonitrile

Conditions	Yield
With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; copper(l) iodide; caesium carbonate In N,N-dimethyl-formamide at 100℃; Inert atmosphere;	51%
With copper(l) iodide; (R,R)-N,N'-dimethyl-1,2-diaminocyclohexane; caesium carbonate In N,N-dimethyl-d6-formamide at 100℃; for 2h; Inert atmosphere;	44.7%

methylmagnesium bromide (75-16-1) + 1H-imidazole-4-carbonitrile (57090-88-7) → 1-(1H-imidazol-4-yl)ethan-1-one (61985-25-9)

Conditions	Yield
Stage #1: methylmagnesium bromide; 1H-imidazole-4-carbonitrile In tetrahydrofuran; diethyl ether at 10 - 20℃; for 2.75h; Stage #2: With sulfuric acid; water In tetrahydrofuran; diethyl ether at 20℃; for 0.5h;	48%

Upstream product

• 3034-50-2 4⁽⁵⁾formylimidazole 
• 26832-08-6 imidazole-4-carboxamide 
• 107-10-8 propylamine 
• 145837-74-7 4-benzamidoimidazo<1,5-a>-1,3,5-triazine 
• 57090-90-1 1(H)-imidazole-4⁽⁵⁾-carbaldehyde oxime 
• 26832-08-6 4⁽⁵⁾-imidazolecarboxamide 
• 2302-25-2 4-bromo-1 H-imidazole 
• 57090-90-1 1H-imidazole-4-carboxaldehyde oxime 
• 33468-69-8 4-(trifluoromethyl)-1H-imidazole 
• 56745-98-3 4-cyano-5-imidazolecarboxylic acid 

Downstream Products

• 87864-83-3 4-cyano-1-(methylcarbamoyl)imidazole 
• 854044-50-1 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carbonitrile 
• 885693-61-8 1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-5-carbonitrile 
• 854044-51-2 2-bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole-4-carbonitrile 
• 66121-69-5 1-methyl-1H-imidazole-4-carbonitrile 
• 13400-46-9 4-aminomethyl-1H-imidazole 
• 66121-66-2 1-methyl-1H-imidazole-5-carbonitrile 
• 1527467-98-6 1-{6-[5-(2-fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-pyridin-3-yl}-1H-imidazole-4-carbonitrile 
• 914781-69-4 1-benzyl-5-cyanoimidazole 

Relevant articles and documents

A convenient synthesis of 4(5)-alkylacyl-1H-imidazoles from 4(5)-imidazolecarboxaldehyde

A convenient synthesis of 4(5)-acyl-1H-imidazoles from 4(5)-imidazolecarboxaldehyde without N-protecting group is described. 4(5)-Cyanoimidazole could be synthesized from commercially available 4(5)-imidazolecarboxaldehyde in one-pot. Treatment of 4(5)-cyanoimidazole with various alkylmagnesium bromides followed by addition of aqueous sulfuric acid afforded 4(5)-acyl-1H-imidazoles in good yield.

Synthesis, ocular effects, and nitric oxide donation of imidazole amidoximes

Novel 1-R-imidazole-5-amidoximes and 1-R-5-cyano-imidazole-4-amidoximes (R: H, Me, Bn) were prepared from their corresponding nitriles and were tested for their efficacy to lower intraocular pressure (IOP) in rabbits. The ability of these compounds to donate nitric oxide (NO) was studied by observing the stimulation of formation of cyclic guanosine-3′,5′-monophosphate (cGMP) in the incubation of porcine iris-ciliary body. In the incubation experiments, 1-methylimidazole-5-amidoxime and 1(H)-imidazole-4(5)-amidoxime stimulated formation of cGMP indicating NO donating ability of these compounds. 1-Methylimidazole-5-amidoxime lowered IOP significantly after intravitreal injection.

Method for preparing 1H-imidazole-4-carbonitrile

The invention discloses a method for preparing 1H-imidazole-4-carbonitrile, and particularly relates to the technical field of fine chemical product preparation. The method for preparing 1H-imidazole-4-carbonitrile comprises the following steps: step (1) oxidation reaction: performing oxidation on 4-hydroxymethylimidazole to obtain 1H-imidazole-4-carboxaldehyde; step (2) oximation reaction: performing oximation reaction on the 1H-imidazole-4-carboxaldehyde prepared in the step (1) to obtain 4-formaldoximido imidazole; and step (3) dehydration reaction: performing dehydration reaction on the 4-formaldoximido imidazole prepared in the step (2) to obtain 1H-imidazole-4-carbonitrile. The method provided by the invention has the advantages of reducing many steps due to intermediates are not purified from the beginning of the reaction to the end of the process, reducing energy consumption due to high and low temperature equipment is not used, reducing environmental pollution due to acidic wastewater is not generated, and having a high yield of products; the invention proposes a complete process route for synthesizing 1H-imidazole-4-carbonitrile by using 4-hydroxymethylimidazole as a rawmaterial; and the method is simple in process and easy to realize industrial production.

PROCESS FOR THE PREPARATION OF CYANO-SUBSTITUTED-NITROGEN-CONTAINING HETEROARYL COMPOUNDS

The present invention provides compounds and methods that can be used to convert nitrogen-containing-heteroaryl carboxamides to the corresponding nitrogen-containing-heteroaryl nitriles reliably in one step, with high yields and without the need for elaborate purification.