1003-21-0

Basic information

• Product Name: 5-BROMO-1-METHYL-1H-IMIDAZOLE
• Synonyms: 5-BROMO-N-METHYLIMIDAZOLE;5-BROMO-1-METHYL-1H-IMIDAZOLE;5-BROMO-1-METHYLIMIDAZOLE;5-Bromo-1-methylimidazole,97%;5-BroMo-1-Methyl-1H-iMidazole 97%;1H-Imidazole,5-bromo-1-methyl-
• CAS NO: 1003-21-0
• Molecular Formula: C₄H₅BrN₂
• Molecular Weight: 161
• Product Categories: blocks;Bromides;Imidazoles;pharmacetical;Imidazol&Benzimidazole;Halogenated Heterocycles;Heterocyclic Building Blocks;ImidazolesBuilding Blocks;Building Blocks;Chemical Synthesis;Halogenated Heterocycles;Heterocyclic Building Blocks
• Mol File: 1003-21-0.mol

Chemical Properties

• Melting Point: 40-44 °C(lit.)
• Boiling Point: 120°C 15mm
• Flash Point: 180 °F
• Appearance: White to tan crystalline solid
• Density: 1.693 g/cm³
• Vapor Pressure: 0.0106mmHg at 25°C
• Refractive Index: 1.606
• Storage Temp.: Keep Cold
• PKA: 5.25±0.10(Predicted)
• CAS DataBase Reference: 5-BROMO-1-METHYL-1H-IMIDAZOLE(CAS DataBase Reference)
• NIST Chemistry Reference: 5-BROMO-1-METHYL-1H-IMIDAZOLE(1003-21-0)
• EPA Substance Registry System: 5-BROMO-1-METHYL-1H-IMIDAZOLE(1003-21-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• RIDADR: UN 3335
• WGK Germany: 3
• Hazardous Substances Data: 1003-21-0(Hazardous Substances Data)

Usage

Chemical Properties

White to tan crystalline solid

InChI:InChI=1/C4H5BrN2/c1-7-3-6-2-4(7)5/h2-3H,1H3

Upstream product

• 2302-25-2 4-bromo-1 H-imidazole 
• 77-78-1 dimethyl sulfate 
• 141524-72-3 4-bromo-1,3-dimethyl-1H-imidazolium iodide 
• 616-47-7 1-methyl-1H-imidazole 
• 74-88-4 methyl iodide 
• 2302-25-2 5-bromo-1H-imidazole 
• 7664-93-9 sulfuric acid 

Downstream Products

• 861362-06-3 (5-bromo-1-methyl-1H-imidazol-2-yl)methanol 
• 143031-96-3 1-methyl-α-phenylsulfonyl-5-imidazoleacetonitrile 
• 462100-53-4 (R)-3-ethyl-4-(1'-methyl-5'-imidazolylcarbonyl)-2-oxazolidinone 
• 865798-15-8 ethyl 5-bromo-1-methyl-1H-imidazole-2-carboxylate 
• 883738-23-6 3-(3-methyl-3H-imidazol-4-yl)-phenylboronic acid 
• 1047645-35-1 1,1-dimethylethyl [2-({[5-(1-methyl-1H-imidazol-5-yl)-2-thienyl]carbonyl}amino)-3-phenylpropyl]carbamate 
• 1071444-92-2 C₂₃H₂₁N₃O₃ 
• 1187312-98-6 C₃₁H₂₆FN₅O₂S 
• 1196707-69-3 (R)-1-methyl-N-(1-phenylethyl)-1H-imidazole-5-carboxamide 
• 1218910-50-9 C₁₀H₉BrN₂ 
• 1318212-69-9 5-(diphenylphosphino)-1-methyl-1H-imidazole 
• 1450597-16-6 2-(1-methyl-1H-imidazol-5-yl)cyclohex-2-en-1-one 
• 1599530-86-5 3-benzyl-6-((4-fluorophenyl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl)-N-methyl-4-(trifluoromethyl)quinolin-2-carboxamide 
• 1599530-94-5 C₂₈H₂₈ClN₅O₄S 

Relevant articles and documents

Direct, Regioselective N-Alkylation of 1,3-Azoles

Regioselective N-alkylation of 1,3-azoles is a valuable transformation. Organomagnesium reagents were discovered to be competent bases to affect regioselective alkylation of various 1,3-azoles. Counterintuitively, substitution selectively occurred at the more sterically hindered nitrogen atom. Numerous examples are provided, on varying 1,3-azole scaffolds, with yields ranging from 25 to 95%.

Highly regioselective C-5 alkynylation of imidazoles by one-pot sequential bromination and Sonogashira cross coupling

A variety of 2-substituted 5-alkynyl-1H-imidazoles were easily prepared by a one-pot sequential procedure involving a highly regioselective electrophilic C-5 bromination of 1,2-dimethyl-1H-imidazole, 2-chloro-1-methyl-1H-imidazole, and 2-aryl-1-methyl-1H-imidazoles, followed by an efficient palladium/copper co-catalyzed Sonogashira-type alkynylation.

Synthesis of chiral pilocarpine analogues via a C-8 ketone intermediate.

The synthesis of a chiral pilocarpine analogue 3 in which the lactone ring is replaced by an oxazolidinone and the bridging methylene group is in the ketone oxidation state has been accomplished. The utility of this compound as a key intermediate for the preparation of more complex structures was demonstrated by its reduction to two alcohol epimers and its reaction with a methylene ylide.

Preparatory study for the synthesis of the starfish alkaloid imbricatine. Syntheses of 5-arylthio-3-methyl-L-histidines

Chiral syntheses of 3-methyl-5-(phenylthio)-L-histidine (8a) and 3-methyl-5-(1-naphthalenylthio)-L-histidine (8b), selected as models for the asteroid alkaloid imbricatine (7), have been accomplished through a 10-step route starting from 4(5)-bromoimidazole (9). The key steps involved were methylation of 9, hydroxymethylation of 4-bromo-1-methyl-1H-imidazole (11), replacement of the 4-bromo group by an arylthio group in the aldehyde 14, and introduction of a chiral α-amino acid moiety into the chlorides 17a and 17b by the 'bis-lactim ether' method. The synthesis of the 4-(4-methoxybenzyl)thio analogue 17c, carried out in a similar manner, concluded formal syntheses of ovothiols A and C (1 and 3).

SYNTHESIS OF 5-ARYLTHIO-3-METHYL-L-HISTIDINE, A MODEL FOR THE STARFISH ALKALOID IMBRICATINE

Syntheses of 3 methyl-5-phenylthio-L-histidine (8a) and 3-methyl-5-(1-naphthyl)thio-L-histidine (8b), selected as models for the asteroid alkaloid imbricatine (7), have now become feasible through a 10-step route starting from 4(5)-bromoimidazole (9).The key steps involve replacement of the 4-bromo group by an arylthio group in the aldehyde (14) and construction of the L-alanine moiety in the chlorides (17a,b) by the "bis-lactim ether" method.

Alkylation, Acylation and Silylation of Azoles

Performing alkylation, acylation and silylation reactions in separate deprotonation and nucleophilic displacement steps allows for better control of reaction conditions and facilitates problem handling in these processes.In the alkylation of azoles the alkylating agents and solvents possess individual reaction capabilities which seem to be approximately additive.Monoalkylation occurs if the sum of the normalized reaction potentials is equal or larger than the pKa value of the azole.Dialkylation is avoided by keeping the sum of the normalized reaction potentials below the pKa value of the alkylazole.The applicability of these principles is demonstrated by the development of effective procedures for the methylation, benzylation, acetylation, methoxycarbonylation and trimethylsilylation of azoles.

A General Route to 4-Substituted Imidazoles

Literature routes to di(imidazol-4-yl)methanol (1a) dinitrate and tri(imidazol-4-yl)methanol (2a) trihydrochloride were improved to give 32 and 16percent overall yields, respectively; but we failed to synthesize bis- (1b) and tris-(1-methylimidazol-4-yl)methanol (2b) by the methylation of the corresponding N-methoxymethyl compounds (3; x=2 and x=3).Attempted 4-lithiation of the 1,2,5-protected imidazole (4a) with BuLi-TMEDA failed, giving after hydrolysis 1-methyl-5-trimethylsilylimidazole (4b); similar failures were observed for 2,5-dicarboxy-1-methylimidazole, which after metallation with BuLi-TMEDA and hydrolysis afforded 1-methylimidazole-5-carboxylic acid (5).Our attempts to obtain 4-bromo-1-methylimidazole (10a) and 4-bromo-1-ethylimidazole suitable for a halogen-lithium exchange or for Grignard reaction also failed.Attempted selective lithiation of 2-phenylthio-1-tritylimidazole (16) at the 4-position, then theatment with ethyl formate, led only to a mixture of 4- and 5-substituted products in very low yield, and 1-diethoxymethyl-2-phenylthioimidazole (18) was unstable and difficult to purify. 4-Bromoimidazole with two mol equiv. of t-butyl-lithium gives 1,4-dilithioimidazole, which is now shown to provide a general route to 4-substituted imidazoles.

INTRODUCTION OF SUBSTITUENTS INTO 5-MEMBERED AZA-HETEROAROMATICS

With emphasis on mono- and regio-selectively, methods for introduction of substituents at nitrogen and carbon atoms of 5-membered aza-heteroaromatics have been developed.The methods involve application of activation and of assistant groups for direction and protection.Activation has been achieved by the use of quaternary azolium ions and azol-N-oxides as reactive intermediates.If necessary, the N-oxides were further activated by alkylation or acylation.

Metal-Halogen Exchange Reactions of Mono- and Poly-halogenoimidazoles

4(5)-Bromoimidazole gave a mixture of 4- and 5-bromo-1-methylimidazole on treatment with 1 or 2 mol equiv. of n-butyl-lithium in ether or THF under various reaction conditions followed by addition of dimethyl sulphate. 5-Iodo and 2,4,5-tribromo-1-methylim

Metallation and Metal-Halogen Exchange Reactions of Imidazoles

Some reactions (reagents in parentheses) are reported of 1-ethoxymethyl-2-phenylthioimidazol-5-yl-lithium 2S2>, 1-ethoxymethyl-5-methylthio-2-phenylthioimidazol-4-yl-lithium (Me2S2, HCONMe2, CO2), 4,5-dibromo-1-ethoxymethylimid