1H-Imidazole-2-carbaldehyde

Cat.NO.:A110938 Purity:95%

Product Details of 1H-Imidazole-2-carbaldehyde

CAS No. :	10111-08-7
Formula :	C₄H₄N₂O
M.W :	96.09
SMILES Code :	O=CC1=NC=CN1
Synonyms :	2-Formylimidazole
MDL No. :	MFCD00003544
InChI Key :	XYHKNCXZYYTLRG-UHFFFAOYSA-N
Pubchem ID :	24955

Safety of 1H-Imidazole-2-carbaldehyde

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Application In Synthesis of 1H-Imidazole-2-carbaldehyde

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 10111-08-7 ]
Downstream synthetic route of [ 10111-08-7 ]

[ 10111-08-7 ] Synthesis Path-Upstream 1~1

1
[ 10111-08-7 ]
[ 3724-26-3 ]

Yield	Reaction Conditions	Operation in experiment
78%	at 5 – 20℃; for 3 h;	To a solution of compound 1 H-imidazole-2-carbaldehyde (5g, 52.08 mmol) in MeOH (50 mL) was added sodium borohydride (3.93g, 104.16 mmol) portion-wise, at 5 00, and the reaction mixture was allowed to stir at RT for 3h. The reaction mixture was quenched with brine (25 mL) and concentrated in vacuo. The crude compound was purified by silica gel column chromatography eluting with 10percent MeOH/CHCI3) to obtain (1H-imidazol-2-yl)-methanol as a pale yellow solid (4g, 78percent).R:0.1 (10percent MeOH/CHCI3).1H NMR (400MHz, CD3OD): O 6.97 (5, 2H), 4.61 (5, 2H).
51%	With sodium tetrahydroborate In methanol at 20℃; for 1 h; Inert atmosphere	To a solution of 2-imidazolecarboxyaldehyde (18-1) (1.92 g, 20 mmol, 1.0 eq.) was suspended in methanol (30 ml), NaBH₄ (1.52g, 40 mmol, 2.0 eq.) was added portion-wise. The reaction mixture was stirred at room temperature for 1 h under N₂. It was quenched with 5 ml of brine. The solvent was removed and the solid was purified with silica gel column chromatography (DCM : MeOH = 20: 1) to afford 18-2 as a white solid. (1.0g, Yield: 51percent).
51%	at 20℃; for 1 h; Inert atmosphere	Compound 26-2 (0449) To a solution of 2-imidazolecarboxyaldehyde (26-1) (1.92 g, 20 mmol, 1.0 eq) was suspended in methanol (30 mL), NaBH₄(1.52 g, 40 mmol, 2.0 eq) was added portion-wise. The reaction mixture was stirred at room temperature for 1 h under N₂. It was quenched with 5 mL of brine. The solvent was removed and the solid was purified with silica gel column chromatography (DCM:MeOH=20:1) to afford a white solid. (1.0 g, Yield: 51percent).

45.2%

With sodium tetrahydroborate In methanol; dichloromethane

Part A
Preparation 2-hydroxymethyl-1H-imidazole
2-Imidazolecarboxyaldehyde (5.0 g, 52.0 mmol) was suspended in 200 mL of methanol. NaBH₄ (3.95 g, 0.10 mol) was added portion-wise.
The reaction mixture was stirred at room temperature for 1 h under N₂.
It was quenched with 10 mL of brine.
The solvent was removed.
The solid was washed with 5percent MeOH in CH₂Cl₂.
The inorganic solid was filtered off.
The filtrate was concentrated and chromatographed with 5percent MeOH in CH₂Cl₂ to give 2.32 g off-white solid (45.2percent yield).
¹H NMR (DMSO-d₆): δ 6.86 (s, 2H), 4.40 (s, 2H).

References:

[1] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 3, p. 827 – 833.

[2] Patent: WO2015/36759, 2015, A1, . Location in patent: Page/Page column 200.

[3] Journal of Organic Chemistry, 2010, vol. 75, # 10, p. 3208 – 3213.

[4] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 19, p. 5849 – 5853.

[5] Patent: US9138427, 2015, B2, . Location in patent: Page/Page column 302.

[6] Journal of Medicinal Chemistry, 2005, vol. 48, # 6, p. 1729 – 1744.

[7] Patent: US2003/144287, 2003, A1, .

[8] Biological and Pharmaceutical Bulletin, 1998, vol. 21, # 9, p. 958 – 963.

[9] Journal of Medicinal Chemistry, 2004, vol. 47, # 15, p. 3707 – 3709.

[ 10111-08-7 ] Synthesis Path-Downstream 1~7

1
[ 66640-86-6 ]
[ 10111-08-7 ]
5-((3aR,6S,6aS)-2-Oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoic acid [1-(1H-imidazol-2-yl)-meth-(E)-ylidene]-hydrazide [ No CAS ]

References: [1]Journal of labelled compounds and radiopharmaceuticals,1999,vol. 42,p. S147-S149.

2
[ 108499-32-7 ]
[ 10111-08-7 ]
[ 369655-08-3 ]

Yield	Reaction Conditions	Operation in experiment
		Synthesis Example 15-1: Synthesis of 2-methoxycarbonyl-5-(N-(imidazol-2-ylmethyl) aminomethyl) thiophene (Compound V-5) 2.02 g of the compound obtained in Synthesis Example 14-1 was dissolved in 30 ml of DMF, and then 1.92 gof potassiumphthalimide was added to the solution. After 3.5 hours, the reaction solution was concentrated and then water was added thereto, followed by extraction with chloroform. An organic layer was dried with anhydrous sodium sulfate and concentrated. The resulting residue was re-crystallized frommethanol, and 1.52 gof the above-mentioned compound was obtained as a yellow solid product. 714 mg of the compound was dissolved in 3.6 ml of ethanol, and then 0.57 ml of hydrazine monohydrate was added to the solution. After the 20-hours reaction, the reaction solution was concentrated. The resulting solid product was washed with chloroform. Filtrate was concentrated and then the resulting residue was dissolved in 14 ml of methanol. Subsequently, 232 mg of 2-imidazole carboxyaldehyde and 0.34 ml of triethylamine were added to the solution and the resultant mixture was stirred for 20 hours. Then, 183 mg of sodium borohydride was added to the reaction mixture. After additional 2 hours, a small amount of silica gel was added to the reaction solution and the solution was concentrated. The resulting residue was purified by means of silica gel column chromatography (15 g, chloroform/methanol = 20/1). Consequently, 105 mg of the above-mentioned compound was obtained as yellow syrup.

References: [1]Patent: EP1389460,2004,A1 .Location in patent: Page/Page column 39.

3
[ 5654-97-7 ]
[ 10111-08-7 ]
C₁₁H₈N₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium ethanolate; In ethanol; at 20℃;	General procedure: Various aldehydes (1.0 equiv) were added to stirred solutions of indolin-2-one, 5-chloroindolin-2-one or <strong>[5654-97-7]7-azaoxindole</strong> (1.0equiv) in absolute ethanol. After stirring at room temperature for 5 min NaOEt/EtOH (0.5 mL) was added and the mixture was then stirred at room temperature overnight. The solvent was then removed under vacuum. The residue was washed with saturated sodium chloride solution and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under vacuum. The solid part was purified by chromatography over silica gel using ethyl acetate/petroleum ether as the eluent to afford desired compounds 1a-1g, 2a, 3a.

References: [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 6953 – 6960.

4
[ 14704-31-5 ]
[ 10111-08-7 ]
1-([1,1′-biphenyl]-3-ylmethyl)-1H-imidazole-2-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With potassium carbonate; In acetonitrile; at 20℃;	A mixture of 1H-imidazole-2-carbaldehyde 40 (200 mg, 2.08 mmol), potassium carbonate (0.8630 g, 6.24 mmol) and <strong>[14704-31-5]3-(bromomethyl)-1,1′-biphenyl</strong> 38 (0.7716 g, 3.12 mmol) in acetonitrile (10 mL) was stirred overnight at room temperature, then the solvent was removed, diluted with water, and extracted with ethyl acetate (3 x 30 mL). The combined organic phases were washed with brine, dried with Na2SO4, filtered, concentrated and purified by silica gel chromatography to afford 44 as a pale yellow solid (527 mg, 97%).