3034-50-2

Basic information

• Product Name: 1H-Imidazole-4-carbaldehyde
• Synonyms: 4(5)-IMIDAZOLECARBOXALDEHYDE;4-IMIDAZOLECARBOXALDEHYDE;4-FORMYLIMIDAZOLE;1H-IMIDAZOLE-4-CARBOXALDEHYDE;1H-IMIDAZOLE-4-CARBALDEHYDE;IMIDAZOLE-4-CARBOXALDEHYDE;FORMYLIMIDAZOLE;4-Formylimidazole 98%
• CAS NO: 3034-50-2
• Molecular Formula: C₄H₄N₂O
• Molecular Weight: 96.09
• EINECS: 221-227-3
• Product Categories: Nitrogen cyclic compounds;Heterocycles;Carbonyl Compounds;Heterocycles series;Aldehydes;Imidazoles & Benzimidazoles;Imidazol&Benzimidazole;Imidaxoles;Imidazoles & Benzimidazoles;Giracodazole;NULL;Heterocycle-other series
• Mol File: 3034-50-2.mol
• Article Data: 25

Chemical Properties

• Melting Point: 174-177 °C(lit.)
• Boiling Point: 367.8 °C at 760 mmHg
• Flash Point: 179.8 °C
• Appearance: White to light yellow powder
• Density: 1.322 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.535
• Storage Temp.: Room temperature.
• Solubility: Soluble in DMSO, methanol.
• PKA: 11.05±0.10(Predicted)
• Sensitive: Air Sensitive
• CAS DataBase Reference: 1H-Imidazole-4-carbaldehyde(CAS DataBase Reference)
• NIST Chemistry Reference: 1H-Imidazole-4-carbaldehyde(3034-50-2)
• EPA Substance Registry System: 1H-Imidazole-4-carbaldehyde(3034-50-2)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-20/21/22
• Safety Statements: 26-36-36/37/39
• WGK Germany: 3
• Hazardous Substances Data: 3034-50-2(Hazardous Substances Data)

Usage

Chemical Properties

White to light yellow powder

Uses

Different sources of media describe the Uses of 3034-50-2 differently. You can refer to the following data:
1. 1H-Imidazole-4-carbaldehyde is a 4-formyl derivative of imidazole used in the preparation of C17,20-lyase inhibitor for the treatemnet of androgen-dependent prostate cancer. 4-Imidazolecarboxaldehyde is also used in the synthesis of other biologically active compounds such as antimalarial drugs.
2. Imidazole-4-carboxaldehyde is a 4-formyl derivative of imidazole used in the preparation of C17,20-lyase inhibitor for the treatment of androgen-dependent prostate cancer. It is also used in the synthesis of other biologically active compounds such as antimalarial drugs, fabrication of colorimetric chemosensor.

InChI:InChI=1/C5H6N2O/c1-4(8)5-2-6-3-7-5/h2-3H,1H3,(H,6,7)

Synthetic route

(1H-imidazol-4-yl)methanol (822-55-9) → 4(5)formylimidazole (3034-50-2)

Conditions	Yield
With manganese(IV) oxide In methanol	99%
With manganese(IV) oxide In methanol at 40℃; for 6h;	92%
With potassium osmate(VI) dihydrate; potassium carbonate; potassium hexacyanoferrate(III) In water; acetonitrile at 60℃; for 18h; chemoselective reaction;	51%

(1-tritylimidazol-4-yl)carboxaldehyde (33016-47-6) → 4(5)formylimidazole (3034-50-2)

Conditions	Yield
With acetic acid In methanol for 7h; Heating;	98%
With acetic acid In methanol for 13h; Heating;	82%

4-bromo-1 H-imidazole (2302-25-2) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 4(5)formylimidazole (3034-50-2)

Conditions	Yield
Stage #1: 4-bromo-1 H-imidazole With isopropylmagnesium chloride In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: With n-butyllithium In tetrahydrofuran; hexane at -20℃; for 0.5h; Stage #3: N,N-dimethyl-formamide In tetrahydrofuran; hexane at -20℃; for 0.5h;	85%

1-(N,N-dimethylsulfamoyl)-2-(triethylsilyl)imidazole-4-carbaldehyde (1025907-10-1) → 4(5)formylimidazole (3034-50-2)

Conditions	Yield
With hydrogenchloride for 1h; Ambient temperature;	80.5%

4-hydroxymethyl-1H-imidazole hydrochloride (32673-41-9) → 4(5)formylimidazole (3034-50-2)

Conditions	Yield
Stage #1: 4-hydroxymethyl-1H-imidazole hydrochloride With sodium carbonate In water neutralization; Stage #2: With manganese(IV) oxide In isopropyl alcohol Oxidation; Heating;	77%
Stage #1: 4-hydroxymethyl-1H-imidazole hydrochloride With sodium hydrogencarbonate In methanol Stage #2: With manganese(IV) oxide In 1,4-dioxane for 2h; Heating / reflux;

4-[(1'R,2'S,3'R)-1',2',3',4'-tetrahydroxybutyl]-imidazole (2644-71-5) → 4(5)formylimidazole (3034-50-2)

Conditions	Yield
With sodium periodate In water at 27 - 30℃; for 2h;	54%

N-((E)-2-Amino-1-formyl-vinyl)-formamide → 4(5)formylimidazole (3034-50-2)

Conditions	Yield
With sodium hydroxide In ethanol for 1h; Heating; Yield given;

urocanic Acid (3465-72-3) → 4(5)formylimidazole (3034-50-2)

Conditions	Yield
With oxygen; purine In water Product distribution; Quantum yield; Mechanism; Irradiation; further solvent and additives; with 18O-labeled oxygen as well;

4(5)-(D-arabinotetritol-1-yl)-imidazole (340699-23-2) → 4(5)formylimidazole (3034-50-2)

Conditions	Yield
With sodium periodate In water

C11H23N(15)N2O2SSi + N-methyl-N-(2-pyridyl)-formamide (67242-59-5) → 4(5)formylimidazole (3034-50-2)

Conditions	Yield
Stage #1: C11H23N(15)N2O2SSi Stage #2: N-methyl-N-(2-pyridyl)-formamide

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;

1H-imidazole (288-32-4) + (1H-imidazol-4-yl)methanol (822-55-9) → 4(5)formylimidazole (3034-50-2)

Conditions	Yield
With manganese dioxide In 1,4-dioxane

4-methyl-1H-imidazole (822-36-6) → 4(5)formylimidazole (3034-50-2)

Conditions	Yield
With pyridine; chromium(VI) oxide; hydrogenchloride; titanium(IV) oxide In dichloromethane; water at 40℃; for 4h; Temperature; Time;

trityl chloride (76-83-5) + 4(5)formylimidazole (3034-50-2) → (1-tritylimidazol-4-yl)carboxaldehyde (33016-47-6)

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	100%
With triethylamine In N,N-dimethyl-formamide at 0 - 20℃;	100%
With triethylamine In N,N-dimethyl-formamide at 20℃;	99%

4(5)formylimidazole (3034-50-2) → imidazole-4-methanamine dihydrochloride (66247-84-5, 72631-80-2)

Conditions	Yield
Stage #1: 4(5)formylimidazole With ammonia; Raney nickel In methanol at 40℃; for 0.5h; Stage #2: With hydrogen In methanol at 40 - 50℃; under 3750.38 Torr; for 28h; Stage #3: With hydrogenchloride In methanol; diethyl ether	100%

N-(8-amino-6-cyano-chroman-3-yl)-N-benzyl methanesulfonamide + 4(5)formylimidazole (3034-50-2) → N-Benzyl-N-{6-cyano-8-[(3H-imidazol-4-yl)-methyl-amino]-chroman-3-yl}-methanesulfonamide (757956-47-1)

Conditions	Yield
Stage #1: N-(8-amino-6-cyano-chroman-3-yl)-N-benzyl methanesulfonamide; 4(5)formylimidazole With trifluoroacetic acid In dichloromethane at 20℃; for 0.166667h; Stage #2: With triethylsilane In dichloromethane	100%

4,5-dimethoxy-2-nitrobenzohydrazide (16308-07-9) + 4(5)formylimidazole (3034-50-2) → C13H13N5O5

Conditions	Yield
With hydrogenchloride In ethanol at 20℃;	100%

4(5)formylimidazole (3034-50-2) → 1H-imidazole-4-carboxaldehyde oxime (57090-90-1)

Conditions	Yield
With pyridine; hydroxylamine hydrochloride In methanol at 20 - 55℃; for 2h;	99%
With hydroxylamine hydrochloride; sodium carbonate In water at 20℃;	69%
With pyridine; hydroxylamine hydrochloride at 27 - 43℃; for 2h;

4(5)formylimidazole (3034-50-2) + methyl iodide (74-88-4) → 1-methyl-1H-imidazole-4-carbaldehyde (17289-26-8)

Conditions	Yield
Stage #1: 4(5)formylimidazole With sodium hydride In tetrahydrofuran; mineral oil at -78 - 20℃; for 0.166667h; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran; mineral oil at -78 - 20℃; for 18h; Inert atmosphere;	99%
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 1.5h;	53%
With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 2h;	34%
Stage #1: 4(5)formylimidazole With sodium hydride In tetrahydrofuran; mineral oil at -78 - 25℃; for 0.5h; Stage #2: methyl iodide In tetrahydrofuran; mineral oil at -78 - 25℃; for 16h;	15.71%
Stage #1: 4(5)formylimidazole With sodium hydride In tetrahydrofuran at 20℃; Stage #2: methyl iodide In tetrahydrofuran at 21℃; for 4h;

leelamine (1446-61-3) + 4(5)formylimidazole (3034-50-2) → imidazole-4-formaldehyde-dehydroabietylamine-Schiff-base

Conditions	Yield
With acetic acid In ethanol for 24h; Reflux;	99%
With acetic acid In ethanol for 24h; Reflux;	98.6%

ethylenediamine (107-15-3) + 4(5)formylimidazole (3034-50-2) → (1E,1′E)-N,N′-(ethane-1,2-diyl)bis(1-(1H-imidazol-4-yl)methanimine)

Conditions	Yield
In acetonitrile for 1h; Reflux;	99%

Di-tert-butyl acetylenedicarboxylate (66086-33-7) + 4(5)formylimidazole (3034-50-2) → ditert-butyl 5H-pyrrolo[1,2-c]imidazole-5,6-dicarboxylate (1301206-53-0)

Conditions	Yield
With triphenylphosphine In diethyl ether at -5 - 20℃; for 3.16667h; Wittig reaction;	98%

4(5)formylimidazole (3034-50-2) + p-toluenesulfonyl chloride (98-59-9) → 1-(p-toluenesulfonyl)-1H-imidazole-4(5)-carboxaldehyde (37622-92-7)

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; Schlenk technique;	98%
With triethylamine In tetrahydrofuran; 1,4-dioxane at 20℃; for 18h; Inert atmosphere;	96%
With triethylamine In ISOPROPYLAMIDE at 10℃;	85%

Cyclohexyl isocyanide (931-53-3) + 2-Butynoic acid (590-93-2) + 3,4-dimethoxybenzylamine (5763-61-1) + 4(5)formylimidazole (3034-50-2) → N-(2-(cyclohexylamino)-1-(1H-imidazol-4-yl)-2-oxoethyl)-N-(3,4-dimethoxybenzyl)but-2-ynamide (1428943-59-2)

Conditions	Yield
With sodium sulfate In methanol at 20℃; Ugi Condensation;	97%

1,4-diaminobutane (110-60-1) + 4(5)formylimidazole (3034-50-2) → N,N‘-(butane-1,4-diyl)bis(1-(1H-imidazol-4-yl)methanimine)

Conditions	Yield
In methanol at 80℃; for 6h;	95.1%

4(5)formylimidazole (3034-50-2) + dimethyl acetylenedicarboxylate (762-42-5) → dimethyl 5H-pyrrolo[1,2-c]imidazole-5,6-dicarboxylate (1301206-51-8)

Conditions	Yield
With triphenylphosphine In diethyl ether at -5 - 20℃; for 3.16667h; Wittig reaction;	95%

6-nitroindoline (19727-83-4) + 4(5)formylimidazole (3034-50-2) → C12H12N4O2 (927427-44-9)

Conditions	Yield
Stage #1: 6-nitroindoline; 4(5)formylimidazole With acetic acid In 1,2-dichloro-ethane for 1h; Stage #2: With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 20℃; Stage #3: With sodium hydrogencarbonate In water; 1,2-dichloro-ethane	94%

(3-benzyloxy-phenyl)-(6-bromo-pyridin-2-ylmethyl)-amine (1020818-08-9) + 4(5)formylimidazole (3034-50-2) → (3-benzyloxy-phenyl)-(6-bromo-pyridin-2-ylmethyl)-(3H-imidazol-4-ylmethyl)-amine (1020816-50-5)

Conditions	Yield
Stage #1: (3-benzyloxy-phenyl)-(6-bromo-pyridin-2-ylmethyl)-amine; 4(5)formylimidazole With sodium cyanoborohydride; zinc(II) chloride In methanol at 40℃; Stage #2: With water; ammonium chloride In methanol at 0℃;	94%

1-[4-(trifluoromethyl)phenyl]piperazine (30459-17-7) + 4(5)formylimidazole (3034-50-2) → 1-((1H-imidazol-4-yl)methyl)-4-(4-trifluoromethylphenyl)-piperazine (1239717-00-0)

Conditions	Yield
Stage #1: 1-[4-(trifluoromethyl)phenyl]piperazine; 4(5)formylimidazole With triethylamine In 1,4-dioxane; methanol at 20℃; Stage #2: With sodium tetrahydroborate In methanol at 20℃;	94%

4(5)formylimidazole (3034-50-2) + dimethylamino sulfonyl chloride (13360-57-1) → 4-formyl-N,N-dimethyl-1H-imidazole-1-sulfonamide (140174-48-7)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 18h;	94%
Stage #1: 4(5)formylimidazole With sodium hydride In acetonitrile; mineral oil at 20℃; for 1.5h; Cooling with ice; Stage #2: dimethylamino sulfonyl chloride In acetonitrile; mineral oil at 20℃;	91%
With triethylamine In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; Schlenk technique;	87%

3-(1H-imidazol-1-yl)propan-1-amine (5036-48-6) + 4(5)formylimidazole (3034-50-2) → N-[(E)-1H-imidazol-5-ylmethylidene]-N-[3-(1H-imidazol-1-yl)propyl]amine (1432046-73-5)

Conditions	Yield
In methanol for 3h; Reflux;	94%

N-[(2-amino-5-cyanophenyl)methyl]-N-[(1R)-1-(phenylmethyl)-2-[(phenylsulphonyl)oxy]ethyl]-2-thiophenesulfonamide (530145-64-3) + 4(5)formylimidazole (3034-50-2) → C31H29N5O5S3

Conditions	Yield
With triethylsilane; trifluoroacetic acid In dichloromethane	94%

Trimethylenediamine (109-76-2) + 4(5)formylimidazole (3034-50-2) → N,N‘-(propane-1,3-diyl)bis(1-(1H-imidazol-4-yl)methanimine)

Conditions	Yield
In methanol at 80℃; for 6h;	94%
In methanol at 50℃;	68%

4(5)formylimidazole (3034-50-2) + methylamine (74-89-5) → N-methyl-1-(4-imidazolyl)methanimine (1374674-33-5)

Conditions	Yield
In methanol at 50℃; for 5h;	93.8%
In ethanol Reflux;

1H-3-(4-fluorobenzyl)-4-(phenylsulfonyl)-7-cyano-2,3,4,5-tetrahydro-1,4-benzodiazepine + 4(5)formylimidazole (3034-50-2) → 1-((imidazole-4-yl)methyl)-3-(4-fluorobenzyl)-4-phenylsulfonyl-7-cyano-2,3,4,5-tetrahydro-1,4-benzodiazepine

Conditions	Yield
Stage #1: 1H-3-(4-fluorobenzyl)-4-(phenylsulfonyl)-7-cyano-2,3,4,5-tetrahydro-1,4-benzodiazepine; 4(5)formylimidazole With trifluoroacetic acid In acetic acid at 20℃; for 0.5h; Stage #2: With triethylsilane In acetic acid at 20℃; for 5h; Stage #3: With sodium hydrogencarbonate In dichloromethane; water	93%

4(5)formylimidazole (3034-50-2) → 4-formylimidazol-potassium

Conditions	Yield
With potassium tert-butylate In ethanol for 0.166667h;	93%

4(5)formylimidazole (3034-50-2) + acetylenedicarboxylic acid diethyl ester (762-21-0) → diethyl 5H-pyrrolo[1,2-c]imidazole-5,6-dicarboxylate (1301206-52-9)

Conditions	Yield
With triphenylphosphine In diethyl ether at -5 - 20℃; for 3.16667h; Wittig reaction;	93%

Dimethyl phosphite (868-85-9) + 4(5)formylimidazole (3034-50-2) → dimethyl(hydroxy(1H-imidazol-4-yl)methyl)phosphonate

Conditions	Yield
With silica supported tungstic acid at 20℃; for 0.5h;	93%

2-aminopyridine (504-29-0) + Cyclohexyl isocyanide (931-53-3) + 4(5)formylimidazole (3034-50-2) → N-cyclohexyl-2-(1H-imidazol-4-yl)imidazo[1,2-a]pyridin-3-amine

Conditions	Yield
With sulfonated β-cyclodextrin In ethanol at 80℃; for 1h;	93%

4(5)formylimidazole (3034-50-2) + 2-<1H-5-methyl-imidazol-4-yl>-2-hydroxyacetic acid (161193-75-5) → 2-(1H-Imidazol-4-yl)-2-hydroxyacetic acid (161193-76-6)

Conditions	Yield
In ethanol; water	92%

methanesulfonic acid (75-75-2) + 4(5)formylimidazole (3034-50-2) + (R)-2,3,4,5-tetrahydro-3-(phenylmethyl)-4-(thien-2-ylsulfonyl)-1H-1,4-benzodiazepine-7-carbonitrile (195985-38-7) → BMS-214662 mesylate

Conditions	Yield
Stage #1: 4(5)formylimidazole; (R)-2,3,4,5-tetrahydro-3-(phenylmethyl)-4-(thien-2-ylsulfonyl)-1H-1,4-benzodiazepine-7-carbonitrile With trifluoroacetic acid; trifluoroacetic anhydride In toluene at 20 - 30℃; for 0.5h; Large scale; Stage #2: With triethylsilane In toluene at 20 - 25℃; Large scale; Stage #3: methanesulfonic acid In toluene at 20 - 25℃; for 1h; Large scale;	92%

Upstream product

• 853803-63-1 tert-butyl 5-formyl-1H-imidazole-1-carboxylate 
• 3465-72-3 urocanic Acid 
• 67242-59-5 N-methyl-N-(2-pyridyl)-formamide 
• 822-36-6 4-methyl-1H-imidazole 
• 2644-71-5 4-[(1'R,2'S,3'R)-1',2',3',4'-tetrahydroxybutyl]-imidazole 
• 288-32-4 1H-imidazole 
• 822-55-9 (1H-imidazol-4-yl)methanol 
• 32673-41-9 4-hydroxymethyl-1H-imidazole hydrochloride 
• 340699-23-2 4⁽⁵⁾-(D-arabinotetritol-1-yl)-imidazole 
• 33016-47-6 (1-tritylimidazol-4-yl)carboxaldehyde 
• 1025907-10-1 1-(N,N-dimethylsulfamoyl)-2-(triethylsilyl)imidazole-4-carbaldehyde 
• 32673-41-9 1H-imidazol-5-ylmethanol hydrochloride 
• 822-55-9 1H-imidazole-5-methanol 
• 2302-25-2 4-bromo-1 H-imidazole 

Downstream Products

• 85102-93-8 1-benzyl-4-imidazolecarboxaldehyde 
• 85102-99-4 1-benzyl-1H-imidazole-5-carboxaldehyde 
• 195983-98-3 2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-4-[(1,1-dimethylethoxy)-carbonyl]-7-phenyl-1H-1,4-benzodiazepine 
• 263845-08-5 [3-(3,4-dihydro-2H-quinoline-1-sulfonyl)-phenyl]-bis-(3H-imidazol-4-ylmethyl)-amine 

Relevant articles and documents

Regioselective n-alkylation of 4-formylimidazole

We describe here a high yield and highly regioselective N-alkylation of 4-formylimidazole via reversible Michael Reaction.

A simple and efficient synthesis of N-protected imidazole-4-carbaldehyde

Successive addition of BuLi, triethylsilyl chloride, s-BuLi and DMF to 1- (N,N-dimethylsulfamoyl)imidazole (1) yields pure 1-(N,N-dimethylsulfamoyl)- 2-(triethylsilyl)imidazole-4-carbaldehyde (2) as judged by 1H NMR spectroscopy. Treatment of 2 with 2 N HCl leads to free imidazole-4- carbaldehyde (3) (overall yield 70.2%).

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.

Hydrazinyl-Substituted Heteroaryl Compounds and Methods for Producing a Conjugate

The present disclosure provides conjugate structures and hydrazinyl-substituted heteroaryl compounds used to produce these conjugates. The disclosure also encompasses methods of production of such conjugates and compounds, as well as methods of using the same.

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