83857-96-9

Basic information

• Product Name: 2-Butyl-4-chloro-5-formylimidazole
• Synonyms: 2-BUTYL-5-CHLOROIMIDAZOLE-4-CARBOXALDEHYDE;2-BUTYL-4-CHLORO-IMIDAZOLE-5-CARBALDEHYDE;2-BUTYL-5-CHLORO-1H-IMIDAZOLE-4-CARBALDEHYDE;2-BUTYL-5-CHLORO-1H-IMIDAZOLE-4-CARBOXALDEHYDE;2-BUTYL-4-CHLORO-1H-IMIDAZOLE-5-CARBALDEHYDE;2-BUTYL-4-CHLORO-1H-IMIDAZOLE-5-CARBOXALDEHYDE;2-BUTYL-4-CHLORO-5-FORMYLIMIDAZLOE;2-BUTYL-4-CHLORO-5-FORMYLIMIDAZOLE
• CAS NO: 83857-96-9
• Molecular Formula: C₈H₁₁ClN₂O
• Molecular Weight: 186.64
• EINECS: 410-260-0
• Product Categories: INTERMEDIATESOF;Aldehydes;Imidazoles & Benzimidazoles;(intermediate of losartan);Heterocyclic Compounds;Hypertension;Heterocycles;Imidazoles & Benzimidazoles;Building Blocks;C8;Carbonyl Compounds;Chemical Synthesis;Halogenated Heterocycles;Heterocyclic Building Blocks;Imidazoles;Organic Building Blocks;api;Intermediates
• Mol File: 83857-96-9.mol
• Article Data: 36

Chemical Properties

• Melting Point: 97-100 °C(lit.)
• Boiling Point: 384.1 °C at 760 mmHg
• Flash Point: 186.1 °C
• Appearance: Yellow solid
• Density: 1.240
• Vapor Pressure: 0.001Pa at 25℃
• Storage Temp.: Refrigerator
• Solubility: slightly soluble
• PKA: 8.87±0.10(Predicted)
• Water Solubility: slightly soluble
• CAS DataBase Reference: 2-Butyl-4-chloro-5-formylimidazole(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Butyl-4-chloro-5-formylimidazole(83857-96-9)
• EPA Substance Registry System: 2-Butyl-4-chloro-5-formylimidazole(83857-96-9)

Safety Data

• Hazard Codes: Xi,N
• Statements: 43-51/53
• Safety Statements: 24-37-61
• RIDADR: UN 3077 9/PG 3
• WGK Germany: 2
• HazardClass: IRRITANT
• PackingGroup: III
• Hazardous Substances Data: 83857-96-9(Hazardous Substances Data)

Usage

Chemical Properties

2-Butyl-4-chloro-5-formylimidazole is Yellow Solid

Uses

Different sources of media describe the Uses of 83857-96-9 differently. You can refer to the following data:
1. 2-Butyl-4-chloro-5-formylimidazole is used for preparation of N-(biphenylylmethyl)imidazoles as angiotensin II antagonists
2. 2-Butyl-5-chloro-1H-imidazole-4-carboxaldehyde may be used in the preparation of the following symmetrical esters of dialkyl 4-(2-butyl-5-chloro-1H-imidazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate:dimethyl 4-(2-butyl-5-chloro-1H-imidazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylatediethyl 4-(2-butyl-5-chloro-1H-imidazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylatediisopropyl 4-(2-butyl-5-chloro-1Himidazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylatediisobutyl 4-(2-butyl-5-chloro-1H-imidazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate di-tert-butyl 4-(2-butyl-5-chloro-1Himidazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylatebis(2-methoxyethyl) 4-(2-butyl-5-chloro-1Himidazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

Application

2-Butyl-4-chloro-1H-imidazole-5-carboxaldehyde (Losartan EP Impurity D) is used for preparation of N-(biphenylylmethyl)imidazoles as angiotensin II antagonists. Losartan USP Related Compound A.

InChI:InChI=1/C8H11ClN2O/c1-2-3-4-7-10-6(5-12)8(9)11-7/h5H,2-4H2,1H3,(H,10,11)

Synthetic route

(NH4)2 Ce(NO3)6 + dichloromethane (75-09-2) + 2-n-butyl-4-chloro-5-hydroxymethylimidazole (79047-41-9) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
With potassium hydroxide In water; acetic acid	92%
In water; acetic acid

(1-iminopentyl)glycine tert-butyl ester + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
Stage #1: (1-iminopentyl)glycine tert-butyl ester With trifluoroacetic acid In 1,2-dichloro-ethane at 20℃; for 24h; Large scale; Stage #2: With trichlorophosphate In toluene at 80℃; for 2h; Large scale; Stage #3: N,N-dimethyl-formamide In toluene at 105℃; for 7h; Temperature; Large scale;	89.2%

(Z)-2-butyl-4-(dimethylaminomethylene)-2-imidazolin-5-one (168900-00-3) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
With trichlorophosphate at 100℃; for 1.5h; Substitution;	88%

4(5)-bromo-2-butyl-1H-imidazole-5(4)-carboxaldehyde (139742-78-2) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
With hydrogenchloride for 24h; Heating;	87%

2-n-butyl-4-chloro-5-hydroxymethylimidazole (79047-41-9) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
With ammonium cerium(IV) nitrate In acetic acid at 25℃; for 3h;	77%
With 2,2,6,6-tetramethyl-piperidine-N-oxyl; iodine; sodium hydrogencarbonate In water; toluene at 20℃; for 16h;	690 mg
With oxygen; Pt/Bi on graphite In methanol at 60℃; under 2250.23 Torr; for 6h; Product distribution; Further Variations:; Reagents;
With manganese dioxide In dichloromethane	12.81 g (86%)

methyl pentanimidate (57246-71-6) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) + glycine (56-40-6) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
Stage #1: glycine With sodium hydroxide In methanol at 0℃; for 0.25h; Stage #2: methyl pentanimidate In methanol at 0 - 20℃; for 16.16 - 16.25h; Stage #3: N,N-dimethyl-formamide With sodium hydroxide; water; trichlorophosphate; copper(II) bis(trifluoromethanesulfonate) Product distribution / selectivity; more than 3 stages;	71%
Stage #1: glycine With sodium hydroxide In methanol at 0℃; for 0.25h; Stage #2: methyl pentanimidate In methanol at 0 - 20℃; for 16.16 - 16.25h; Stage #3: N,N-dimethyl-formamide With sodium hydroxide; trichlorophosphate Product distribution / selectivity; more than 3 stages;	66.4%
Stage #1: methyl pentanimidate; glycine With sodium hydroxide In methanol; water; toluene Stage #2: N,N-dimethyl-formamide With trichlorophosphate In toluene at 100℃; for 2h;	55%

N,N-dimethyl-formamide (68-12-2, 33513-42-7) + 2-butyl-2-imidazolin-5-one (154147-42-9) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) + (E)-2-(but-1-en-1-yl)-5-chloroimidazole-4-carbaldehyde + 5-chloro-2-(2-chlorobutyl)imidazole-4-carbaldehyde

Conditions	Yield
With trichlorophosphate In toluene at 100℃; for 2h; Dehydrogenation; Vilsmeier formylation; chlorination;	A 55% B n/a C n/a

[2-Butyl-5-chloro-imidazol-(4Z)-ylidenemethyl]-dimethyl-amine → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
With water Yield given;
With water Hydrolysis; Acid hydrolysis;

2-butyl-1H-imidazole-5-carboxaldehyde (68282-49-5) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
With N-chloro-succinimide Chlorination;

N,N-dimethyl-formamide (68-12-2, 33513-42-7) + 2-butyl-5-chloro-1H-imidazole (158365-99-2) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
With trichlorophosphate In chlorobenzene at 100℃; for 4h; Formylation; Vilsmeier reaction;

N,N-dimethyl-formamide (68-12-2, 33513-42-7) + (pentanimidoylamino)acetic acid (193140-43-1) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
With trichlorophosphate In toluene at 100℃; for 2h; Cyclization; Vilsmeier formylation; substitution;	26.0 g
With trichlorophosphate In toluene at 97 - 100℃; for 3h;	132 g
With trichlorophosphate In toluene at 60 - 100℃; for 2h; Green chemistry;	0.154 g

2-n-butyl-4-chloro-5-hydroxymethylimidazole (79047-41-9) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) + 2-butyl-4,5-dichloroimidazole

Conditions	Yield
With 2,2,6,6-tetramethyl-piperidine-N-oxyl; N-chloro-succinimide; sodium hydrogencarbonate In water; toluene at 20℃;	A n/a B 85 % Chromat.

2-n-butyl-4-chloro-5-hydroxymethylimidazole (79047-41-9) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) + 5-bromo-2-butyl-4-chloro-1H-imidazole

Conditions	Yield
With 2,2,6,6-tetramethyl-piperidine-N-oxyl; N-Bromosuccinimide; sodium hydrogencarbonate In water; toluene at 20℃;	A n/a B 85 % Chromat.

pentanonitrile (110-59-8) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: HCl / 12 h / 20 °C 1.2: aq. KOH / toluene / 5 °C 2.1: aq. KOH / toluene; methanol / 15 h / 40 °C 3.1: 132 g / POCl3 / toluene / 3 h / 97 - 100 °C View Scheme
Multi-step reaction with 4 steps 1: 190.8 g / HCl / dibutyl ether / 144 h / 4 °C 2: 95 percent / NaOH / methanol; toluene / 3 h / 20 °C 3: 44 percent / CH2Cl2 / 20 - 27 °C 4: 88 percent / POCl3 / 1.5 h / 100 °C View Scheme
Multi-step reaction with 5 steps 1: 190.8 g / HCl / dibutyl ether / 144 h / 4 °C 2: 95 percent / NaOH / methanol; toluene / 3 h / 20 °C 3: 31 percent / POCl3 / chlorobenzene / 2 h / 100 °C 4: Et3N / chlorobenzene / Heating 5: H2O / Acid hydrolysis View Scheme

methyl pentanimidate (57246-71-6) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. KOH / toluene; methanol / 15 h / 40 °C 2: 132 g / POCl3 / toluene / 3 h / 97 - 100 °C View Scheme
Multi-step reaction with 3 steps 1: 95 percent / NaOH / methanol; toluene / 3 h / 20 °C 2: 44 percent / CH2Cl2 / 20 - 27 °C 3: 88 percent / POCl3 / 1.5 h / 100 °C View Scheme
Multi-step reaction with 4 steps 1: 95 percent / NaOH / methanol; toluene / 3 h / 20 °C 2: 31 percent / POCl3 / chlorobenzene / 2 h / 100 °C 3: Et3N / chlorobenzene / Heating 4: H2O / Acid hydrolysis View Scheme

pentanimidamide (109-51-3) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
Multi-step reaction with 3 steps 2: 44 percent / CH2Cl2 / 20 - 27 °C 3: 88 percent / POCl3 / 1.5 h / 100 °C View Scheme
Multi-step reaction with 4 steps 2: 31 percent / POCl3 / chlorobenzene / 2 h / 100 °C 3: Et3N / chlorobenzene / Heating 4: H2O / Acid hydrolysis View Scheme
Multi-step reaction with 3 steps 2: 31 percent / POCl3 / chlorobenzene / 2 h / 100 °C 3: POCl3 / chlorobenzene / 4 h / 100 °C View Scheme

ethyl valerimidate (999-09-7) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 40 percent / 24 h / -10 °C 2: 44 percent / CH2Cl2 / 20 - 27 °C 3: 88 percent / POCl3 / 1.5 h / 100 °C View Scheme
Multi-step reaction with 4 steps 1: 40 percent / 24 h / -10 °C 2: 31 percent / POCl3 / chlorobenzene / 2 h / 100 °C 3: Et3N / chlorobenzene / Heating 4: H2O / Acid hydrolysis View Scheme
Multi-step reaction with 3 steps 1: 40 percent / 24 h / -10 °C 2: 31 percent / POCl3 / chlorobenzene / 2 h / 100 °C 3: POCl3 / chlorobenzene / 4 h / 100 °C View Scheme

2-butyl-2-imidazolin-5-one (154147-42-9) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 44 percent / CH2Cl2 / 20 - 27 °C 2: 88 percent / POCl3 / 1.5 h / 100 °C View Scheme
Multi-step reaction with 3 steps 1: 31 percent / POCl3 / chlorobenzene / 2 h / 100 °C 2: Et3N / chlorobenzene / Heating 3: H2O / Acid hydrolysis View Scheme
Multi-step reaction with 2 steps 1: 31 percent / POCl3 / chlorobenzene / 2 h / 100 °C 2: POCl3 / chlorobenzene / 4 h / 100 °C View Scheme
Multi-step reaction with 2 steps 1: 1.) POCl3 / 1.) toluene, 80 deg C, 2.) toluene, 100 deg C 2: H2O View Scheme

2-butyl-5-chloro-1H-imidazole (158365-99-2) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / chlorobenzene / Heating 2: H2O / Acid hydrolysis View Scheme

2-butyl-1H-imidazole (50790-93-7) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: H2O 2: MnO2 / CH2Cl2 3: N-chlorosuccinimide View Scheme
Multi-step reaction with 5 steps 1: 56 percent / Br2 / CHCl3 / Ambient temperature 2: 85 percent / Na2SO3 / H2O; ethanol / 18 h / Heating 3: 78 percent / aq. NaOH / ethanol / Ambient temperature 4: 81 percent / MnO2 / CH2Cl2; dioxane / Heating 5: 87 percent / conc. aq. HCl / 24 h / Heating View Scheme

2-butyl-5-hydroxymethyl-1H-imidazole (68283-19-2) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: MnO2 / CH2Cl2 2: N-chlorosuccinimide View Scheme

4(5)-bromo-2-butyl-1H-imidazole (145575-93-5) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 78 percent / aq. NaOH / ethanol / Ambient temperature 2: 81 percent / MnO2 / CH2Cl2; dioxane / Heating 3: 87 percent / conc. aq. HCl / 24 h / Heating View Scheme

4,5-dibromo-2-butyl-1H-imidazole (145575-92-4) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 85 percent / Na2SO3 / H2O; ethanol / 18 h / Heating 2: 78 percent / aq. NaOH / ethanol / Ambient temperature 3: 81 percent / MnO2 / CH2Cl2; dioxane / Heating 4: 87 percent / conc. aq. HCl / 24 h / Heating View Scheme

4(5)-bromo-2-butyl-1H-imidazole-5(4)-methanol (139742-77-1) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 81 percent / MnO2 / CH2Cl2; dioxane / Heating 2: 87 percent / conc. aq. HCl / 24 h / Heating View Scheme

aqueous H2 O2 + water (7732-18-5) + 2-n-butyl-4-chloro-5-hydroxymethylimidazole (79047-41-9) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In methanol
With hydrogenchloride; sodium hydroxide In methanol

aqueous H2 O2 + 2-n-butyl-4-chloro-5-hydroxymethylimidazole (79047-41-9) + 4-methyl-2-pentanone (108-10-1) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In water

2-butyl-4-chloro-5-hydroxyimdazole → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
With manganese dioxide; silica gel In methanol

Cs2 CO3 + dichloromethane (75-09-2) + Ethyl 4-(bromomethyl)benzoate (26496-94-6) + 2-n-butyl-4-chloro-5-hydroxymethylimidazole (79047-41-9) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
With manganese dioxide In tetrahydrofuran; methanol; water; ethyl acetate; N,N-dimethyl-formamide

1H-imidazole (288-32-4) + 2-n-butyl-4-chloro-5-hydroxymethylimidazole (79047-41-9) → 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9)

Conditions	Yield
With NH4Ca(NO3)3; sodium hydroxide In acetic acid
With NH4Ca(NO3)3; sodium hydroxide In acetic acid

2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) + N-(triphenylmethyl)-5-<4'-(bromomethyl)biphenyl-2-yl>tetrazole (133051-88-4) → 2-n-butyl-4-chloro-1-[(2'-(2-triphenylmethyl-2H-tetrazol-5-yl)-1,1'-biphenyl-4-yl)methyl]-1H-imidazole-5-methanol (133909-99-6)

Conditions	Yield
Stage #1: 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde; N-(triphenylmethyl)-5-<4'-(bromomethyl)biphenyl-2-yl>tetrazole With potassium carbonate In N,N-dimethyl-formamide at 20 - 22℃; for 3h; Stage #2: With sodium tetrahydroborate In water; N,N-dimethyl-formamide at 48 - 52℃; for 3.08333h;	99.2%
With potassium carbonate In N,N-dimethyl acetamide
With potassium carbonate In N,N-dimethyl acetamide

1H-benzimidazol-2-acetonitrile (4414-88-4) + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → (E)-2-(1H-benzo[d]imidazol-2-yl)-3-(2-butyl-4-chloro-1H-imidazol-5-yl)acrylonitrile

Conditions	Yield
With L-proline In ethanol at 20℃; for 0.166667h; Knoevenagel Condensation;	98%

2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 2-n-butyl-5-chloro-3H-imidazole-4-carboxylic acid

Conditions	Yield
With sodium chlorite; sodium dihydrogen phosphate monohydrate; 2-methyl-but-2-ene In tetrahydrofuran; water; tert-butyl alcohol at 20℃; for 12h;	95%
Multi-step reaction with 2 steps 1.1: sodium cyanide; manganese(IV) oxide; acetic acid / 20 h / 60 °C 2.1: sodium hydroxide / ethanol; water / 2.5 h / Reflux 2.2: pH 3 - 4 View Scheme

benzyl bromide (100-39-0) + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 3-benzyl-2-butyl-5-chloro-3H-imidazole-4-carbaldehyde (141692-01-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 4h;	92%
With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 1h;

2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) + 1,3-chlorobromopropane (109-70-6) → 2-butyl-4-chloro-1-(3-chloropropyl)-1H-imidazole-5-carboxaldehyde (1165931-51-0)

Conditions	Yield
With potassium carbonate In acetone for 2h; Reflux;	92%
With potassium carbonate In acetone at 60℃; for 2h;	70%

5-[4'-(bromomethyl)biphenyl-2-yl]-1-(p-methoxybenzyl)-1H-tetrazole (1307853-40-2) + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 2-butyl-4-chloro-1-({2'-[1-(p-methoxybenzyl)-1H-tetrazol-5-yl]-biphenyl-4-yl}-methyl)imidazole-5-carbaldehyde (1307853-51-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl acetamide at -10 - 20℃; for 8h;	92%

5-[4'-(bromomethyl)biphenyl-2-yl]-1-(p-methoxybenzyl)-1H-tetrazole (1307853-40-2) + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → C30H31ClN6O2

Conditions	Yield
With potassium carbonate In ISOPROPYLAMIDE at -10 - 20℃; for 8h; Inert atmosphere;	92%

p-methyloxycarbonylbenzyl chloride (34040-64-7) + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 2-butyl-4-chloro-1-<(4-carbomethoxyphenyl)methyl>-1H-imidazole-5-carboxaldehyde (133040-02-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20 - 25℃; for 10h; Temperature;	91.9%

para-chloroacetophenone (99-91-2) + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 1-(4-chlorophenyl)-3-(2-butyl-4-chloro-1H-imidazol-5-yl)-2-propen-1-one (1206796-57-7)

Conditions	Yield
With potassium hydroxide In PEG-400 at 40℃; for 1h; Claisen-Schmidt condensation;	91%
With potassium hydroxide

2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 2-n-butyl-4-chloro-5-hydroxymethylimidazole (79047-41-9)

Conditions	Yield
With sodium tetrahydroborate In methanol at 20℃; for 2h;	90%
With hydrogen; magnesium In methanol at 20℃; under 258.574 - 413.718 Torr; for 0.583333h;

1-bromo-2-(bromomethyl)-4,5-dimethoxybenzene (53207-00-4) + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 1-(2-bromo-4,5-dimethoxybenzyl)-2-butyl-4-chloro-1H-imidazole-5-carbaldehyde

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 10h;	90%

2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) + (3,4-methylenedioxy)-6-methylbenzyl chloride (117661-72-0) → 2-butyl-4-chloro-1-(6-methyl-1,3-benzodioxol-5-ylmethyl)-1H-imidazole-5-carbaldehyde

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 10h;	90%

2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) + 1-bromomethyl-4-bromobenzene (589-15-1) → 2-n-Butyl-4-chloro-1-p-bromobenzyl-1H-imidazole-5-carboxaldehyde (143722-29-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl acetamide; water; toluene	89.9%
With potassium carbonate In N,N-dimethyl acetamide; water; toluene	89.9%

2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) + methyl iodide (74-88-4) → 2-butyl-4-chloro-1-methyl-1H-imidazole-5-carbaldehyde (1332222-81-7)

Conditions	Yield
Stage #1: 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde With sodium hydride In N,N-dimethyl-formamide at 0℃; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; for 4h;	89.6%
With potassium carbonate In N,N-dimethyl-formamide	89.6%

Methyl 4-(bromomethyl)benzoate (2417-72-3) + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 2-butyl-4-chloro-1-<(4-carbomethoxyphenyl)methyl>-1H-imidazole-5-carboxaldehyde (133040-02-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide	89%
Stage #1: 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde With potassium carbonate In N,N-dimethyl-formamide at 25 - 30℃; for 0.5h; Stage #2: Methyl 4-(bromomethyl)benzoate In N,N-dimethyl-formamide at 0 - 30℃; for 19.5 - 23.5h;	82.12%
With potassium carbonate In N,N-dimethyl-formamide Alkylation;
With caesium carbonate In N,N-dimethyl-formamide
With potassium carbonate In N,N-dimethyl-formamide at 25 - 70℃; for 12.5h;

Methyl 4-(bromomethyl)benzoate (2417-72-3) + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 2-butyl-4-chloro-1-<(4-carbomethoxyphenyl)methyl>-1H-imidazole-5-carboxaldehyde (133040-02-5) + 4-(2-Butyl-5-chloro-4-formyl-imidazol-1-ylmethyl)-benzoic acid methyl ester

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 1h;	A 89% B n/a
With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 1h;

2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) + 4'-bromomethyl-biphenyl-2-carboxylic acid tert-butyl ester (114772-40-6) → 4’-(2-butyl-4-chloro-5-formylimidazol-1-ylmethyl)biphenyl-2-carboxylic acid t-butyl ester (133694-34-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	89%
With potassium carbonate In N,N-dimethyl-formamide at 20℃;

4'-(bromomethyl)-3-hydroxybiphenyl-2-carbaldehyde oxime + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 4-chloro-1-({3'-hydroxy-2'-[E-(hydroxyimino)methyl]biphenyl-4-yl}methyl)-2-butyl-5-carbaldehyde imidazole

Conditions	Yield
With potassium carbonate In N,N-dimethyl acetamide at 20℃; for 2h;	89%

N,N-didesmethylvenlafaxine (93413-77-5, 272788-06-4, 273720-73-3) + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 2-(2-butyl-4-chloro-1H-imidazol-5-yl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecane

Conditions	Yield
With potassium carbonate In methanol at 20℃; for 9h;	89%

2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 2-butyl-4-chloro-1H-imidazolyl-5-methaldoxime (634907-73-6)

Conditions	Yield
With sodium acetate; hydroxylamine sulfate In methanol Heating;	88%
With sodium acetate; hydroxylamine sulfate In methanol at 60℃;

2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) + 4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile (114772-54-2) → 2-n-Butyl-4-chloro-1-[(2'-cyanobiphenyl-4-yl)-methyl]-5-(hydroxymethyl)imidazole (114772-55-3)

Conditions	Yield
Stage #1: 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde; 4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile With potassium carbonate In 1-methyl-pyrrolidin-2-one at 70 - 75℃; Stage #2: With sodium tetrahydroborate In 1-methyl-pyrrolidin-2-one at 30℃; Stage #3: With water In 1-methyl-pyrrolidin-2-one; isopropyl alcohol at 75 - 80℃; for 1.5h;	88%
With tetrabutylammomium bromide; sodium hydroxide In water; toluene at 20℃;
With tetrabutylammomium bromide; water; sodium hydroxide In toluene at 20℃;

2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) + edaravone (89-25-8) → 3-(2-butyl-4-chloro-1H-imidazol-5-yl-methylene)-4-methyl-1-phenyl-1H-pyrrol-2(3H)one (1268160-00-4)

Conditions	Yield
With sodium acetate at 60 - 80℃; for 1.33333h; Green chemistry;	88%

1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol monoacetate + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 2-(2-butyl-4-chloro-1H-imidazol-5-yl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecane

Conditions	Yield
With potassium carbonate	88%

2-chloro-1-(2,4-dihydroxyphenyl)ethanone (25015-92-3) + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → 2-(2-butyl-4-chloro-1H-imidazol-5-yl)-7-hydroxy-4H-chromen-4-one

Conditions	Yield
With sodium hydroxide In ethanol; water at 20℃; for 24h;	86.3%
With sodium hydroxide In ethanol at 20℃; for 24h;	76.9%

4-bromomethylphenylboronic acid (68162-47-0) + 2-n-butyl-4-chloro-1H-imidazol-5-carboxaldehyde (83857-96-9) → (4-((2-butyl-4-chloro-5-formyl-1H-imidazol-1-yl)methyl)phenyl)-boronic acid (894806-32-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 3h;	86%

Upstream product

• 168900-00-3 (Z)-2-butyl-4-(dimethylaminomethylene)-2-imidazolin-5-one 
• 79047-41-9 2-n-butyl-4-chloro-5-hydroxymethylimidazole 
• 110-59-8 pentanonitrile 
• 57246-71-6 methyl pentanimidate 
• 7732-18-5 water 
• 75-09-2 dichloromethane 
• 26496-94-6 Ethyl 4-(bromomethyl)benzoate 
• 154147-42-9 2-butyl-2-imidazolin-5-one 
• 10025-87-3 trichlorophosphate 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 
• 158365-99-2 2-butyl-5-chloro-1H-imidazole 
• 68-12-2 N,N-dimethyl-formamide 
• 193140-43-1 (pentanimidoylamino)acetic acid 
• 154147-42-9 2-n-butyl-3,5-dihydroimidazolin-4-one 

Downstream Products

• 159708-77-7 4-(2-Butyl-4-chloro-5-formyl-imidazol-1-ylmethyl)-benzonitrile 
• 151012-31-6 2-n-Butyl-4-chloro-1-(4-bromobenzyl)-1H-imidazole-5-methanol 
• 143722-29-6 3-(4-bromobenzyl)-2-butyl-5-chloro-3h-imidazole-4-carboxaldehyde 
• 137997-24-1 1-[(3-Ethoxycarbonyl-2-phenylimidazo[1,2-a]pyridin-6-yl)methyl]-2-butyl-4-chloro-5-formylimidazole 
• 146769-07-5 tert-butyl 2-[4-(2-n-butyl-4-chloro-5-formyl-imidazol-1-yl-methyl)phenyl]-2-cyclopentyl-acetate 
• 124751-00-4 2-Butyl-4-chloro-1-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-methanol 
• 124750-67-0 2-n-Butyl-4-chloro-1-[(2'-cyanobiphenyl-4-yl)methyl]imidazole-5-carboxaldehyde 
• 1192346-36-3 N-t-butyl-4-(2-butyl-4-chloro-5-formylimidazol-1-ylmethyl)benzenesulfonamide 
• 148674-53-7 4-[2-Butyl-5-((E)-2-cyano-3-thiophen-2-yl-propenyl)-imidazol-1-ylmethyl]-benzoic acid methyl ester 
• 148674-39-9 SB 206328 
• 149543-80-6 methyl (E)-3-[2-n-butyl-1-{(4-carbomethoxy-3-methoxymethoxyphenyl)methyl}-1H-imidazol-5-yl]-2-(thien-2-yl)methyl-2-propenoate 

Relevant articles and documents

Iodine as a chemoselective reoxidant of TEMPO: application to the oxidation of alcohols to aldehydes and ketones.

[reaction: see text] Chemoselective alcohol oxidations using catalytic TEMPO and stoichiometric iodine as the terminal oxidant were studied. Iodine was compared to other positive halogens as the terminal oxidant and shown to be superior in cases of electron-rich and heteroaromatic rings. The new conditions were successfully applied to an important intermediate (2) in the synthesis of Losartan.

Production process of imidazole aldehyde

The invention provides a production process of imidazole aldehyde. Imiline is prepared by using valeronitrile and methanol as raw materials, glycine and methanol are added to prepare imidic acid, anda further reaction is conducted with phosphorus oxychloride and DMF to obtain the imidazole aldehyde. By controlling reaction conditions and the feed ratio of the raw materials, the formation of by-products is reduced, and the yield is improved. A decoking and decolorization reaction and an activated carbon decolorization reaction are adopted, the solubility change of the imidazole aldehyde underdifferent pH conditions is used for purifying a product, and finally, the imidazole aldehyde with a purity of more than 99.2% is obtained by recrystallization.

Preparation method of 2-n-butyl-4-chloro-5-formylimidazole

The invention provides a preparation method of 2-n-butyl-4-chloro-5-formylimidazole. The preparation method comprises the following steps of using pentanimidamide hydrochloride and tert-butyl glycine hydrochloride as initial raw materials to react, so as to obtain (1-imido amyl)tert-butyl glycinate; performing deprotection, ring closing, chlorinating and vilsemier reaction, and recrystallizing, so as to obtain the 2-n-butyl-4-chloro-5-formylimidazole. The preparation method has the advantages that the price of raw materials is low, the obtaining is easy, the cost is low, the content of impurities is low, and the purity is high; the organic solvent used in the preparation process can be recycled, the pollution is little, the environment-friendly effect is realized, and the preparation method is suitable for industrialized large-scale production.