38585-62-5

Basic information

• Product Name: 4-Methyl-5-imidazolemethanol hydrochloride
• Synonyms: 4-Methyl-5-imidazolemethanolhydrochilride;4-METHYL-5-IMIDAZOLEMETHANOLHYDROCHLORIDE98%;1H-IMIDAZOLE-4-METHANOL, 5-METHYL-MONOHYDROCHLORIDE;4-METHYL-5-IMIDAZOLEMETHANOL HYDROCHLORIDE;4-HYDROXYMETHYL-5-METHYLIMIDAZOLE HYDROCHLORIDE;4-hydroxymethyl-5-methylimidazole monohydrochloride;(5-METHYL-1H-IMIDAZOL-4-YL)METHANOL HYDROCHLORIDE;5-METHYL-4-HYDROXYMETHYL IMIDAZOLE HCL
• CAS NO: 38585-62-5
• Molecular Formula: C₅H₈N₂O*ClH
• Molecular Weight: 148.59
• EINECS: 254-021-7
• Product Categories: Heterocyclic Compounds;Building Blocks;Heterocyclic Building Blocks;Imidazoles
• Mol File: 38585-62-5.mol
• Article Data: 10

Chemical Properties

• Melting Point: 233 °C (dec.)(lit.)
• Boiling Point: 389.1 °C at 760 mmHg
• Flash Point: 189.1 °C
• Appearance: Very slightly beige/Crystalline Powder
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: DMSO (Sparingly), Methanol (Slightly)
• CAS DataBase Reference: 4-Methyl-5-imidazolemethanol hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Methyl-5-imidazolemethanol hydrochloride(38585-62-5)
• EPA Substance Registry System: 4-Methyl-5-imidazolemethanol hydrochloride(38585-62-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39
• WGK Germany: 3
• Hazardous Substances Data: 38585-62-5(Hazardous Substances Data)

Usage

Chemical Properties

VERY SLIGHTLY BEIGE CRYSTALLINE POWDER

Uses

4-Methyl-5-imidazolemethanol hydrochloride was used in the synthesis of 1,3-bis(5-methyl-4-imidazolyl)-2-thiapropane (tridentate ligand).

InChI:InChI=1/C5H8N2O.ClH/c1-4-5(2-8)7-3-6-4;/h3,8H,2H2,1H3,(H,6,7);1H

Synthetic route

diethyl ether (60-29-7) + Ethyl 5-Methyl-4-imidazolecarboxylate (51605-32-4) → 4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5)

Conditions	Yield
With ammonium chloride; sodium In methanol; ethanol; ammonia; water; isopropyl alcohol; acetone	94%

1,4-dioxane (123-91-1) + potassium 5-methylimidazole-4-carboxylate → 4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5)

Conditions	Yield
With potassium hydroxide; formaldehyd	72%

1,4-dioxane (123-91-1) + 5-methylimidazole-4-carboxylic acid sodium salt → 4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5)

Conditions	Yield
With hydrogenchloride; formaldehyd In ethanol	63%

Ethyl 5-Methyl-4-imidazolecarboxylate (51605-32-4) → 4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5)

Conditions	Yield
In sulfuric acid
With ammonium chloride In nitrogen; ammonia; isopropyl alcohol

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) → 4-chloromethyl-5-methyl-imidazole hydrochloride (51605-33-5)

Conditions	Yield
With thionyl chloride for 3.5h; Ambient temperature;	100%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + 1,1-dimethyl-2-mercaptoethylamine hydrochloride (4146-00-3) → 1-<(5-Methylimidazol-4-yl)methylthio>-2-(2-methyl)propylamine-Dihydrobromid

Conditions	Yield
With hydrogen bromide for 6h; Heating;	92%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + (2R)-2-aminobutanethiol hydrochloride → (R)-1-<(5-Methylimidazol-4-yl)methylthio>-2-butyl-Dihydrobromid

Conditions	Yield
With hydrogen bromide for 6h; Heating;	89%

2-(methylamino)ethanethiol (10061-40-2) + 4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) → Methyl-[2-(5-methyl-1H-imidazol-4-ylmethylsulfanyl)-ethyl]-amine; hydrobromide (75613-66-0)

Conditions	Yield
With hydrogen bromide Heating;	88%

captamine (108-02-1) + 4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) → Dimethyl-[2-(5-methyl-1H-imidazol-4-ylmethylsulfanyl)-ethyl]-amine; hydrobromide (75613-68-2)

Conditions	Yield
With hydrogen bromide Heating;	83%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + (2S)-2-aminopropane-1-thiol hydrochloride → (S)-1-<(5-Methylimidazol-4-yl)methylthio>-2-propyl-Dihydrobromid

Conditions	Yield
With hydrogen bromide for 6h; Heating;	82%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + SOCl2 → 4-chloromethyl-5-methyl-imidazole hydrochloride (51605-33-5)

Conditions	Yield
In ethanol 1.) reflux, 1 h, 2.) -5 to -10 deg C, 20 h;	82%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + 1-(mercaptomethyl)propylammonium chloride → rac-1-<(5-Methylimidazol-4-yl)methylthio>-2-butyl-Dihydrobromid

Conditions	Yield
With hydrogen bromide for 6h; Heating;	80%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + (S)-2-Amino-butane-1-thiol; hydrochloride → (S)-1-<(5-Methylimidazol-4-yl)methylthio>-2-butyl-Dihydrobromid

Conditions	Yield
With hydrogen bromide for 6h; Heating;	80%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + mercaptoacetic acid (68-11-1) → [(5-methyl-1H-imidazol-4-yl)methylsulfanyl]acetic acid (112528-37-7)

Conditions	Yield
In acetic acid for 24h; Heating;	80%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + (2R)-2-amino-1-propanethiol hydrochloride → (R)-1-<(5-Methylimidazol-4-yl)methylthio>-2-propyl-Dihydrobromid

Conditions	Yield
With hydrogen bromide for 6h; Heating;	79%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + mercaptoacetic acid (68-11-1) → 2-<<(5-Methyl-4-imidazolyl)methyl>thio>acetic acid hydrochloride (112528-45-7)

Conditions	Yield
at 126.9℃; for 12h;	79%

1-amino-2-propanethiol hydrochloride (4146-16-1) + 4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) → 2-<(5-Methylimidazol-4-yl)methylthio>-1-propylamine-Dihydrobromid

Conditions	Yield
With hydrogen bromide for 6h; Heating;	78%

homocysteamine hydrochloride (7211-54-3) + 4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) → 3-<(5-Methylimidazol-4-yl)methylthio>-1-propylamine-Dihydrobromid

Conditions	Yield
With hydrogen bromide for 6h; Heating;	78%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + trityl chloride (76-83-5) → 4-Hydroxymethyl-5-methyl-1-(triphenylmethyl)imidazole (106147-84-6)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 0℃; for 3h;	73%

2-Ethylamino-ethylmercatan (5977-97-9) + 4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) → Ethyl-[2-(5-methyl-1H-imidazol-4-ylmethylsulfanyl)-ethyl]-amine; hydrobromide (75637-20-6)

Conditions	Yield
With hydrogen bromide Heating;	70%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + Cysteamine (60-23-1) → 2-<(5-Methyl-4-imidazolyl)-methylthio>-ethylamin-dihydrobromid (38603-73-5)

Conditions	Yield
With hydrogen bromide Heating;	68%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + ethyl 2-sulfanylacetate (623-51-8) → (5-Methyl-1H-imidazol-4-ylmethylsulfanyl)-acetic acid ethyl ester

Conditions	Yield
In acetic acid for 24h; Heating;	67%

2-cyclohexylamino-ethanethiol (5977-96-8) + 4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) → Cyclohexyl-[2-(5-methyl-1H-imidazol-4-ylmethylsulfanyl)-ethyl]-amine; hydrobromide (75613-67-1)

Conditions	Yield
With hydrogen bromide Heating;	66%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + 6-fluoro-2,3,4,5-tetrahydro-5-methyl-1H-pyrido<4,3-b>indol-1-<14C>-one → 6-fluoro-2,3,4,5-tetrahydro-5-methyl-2-<5-methyl-1H-imidazol-4-yl>methyl-1H-pyrido<4,3-b>-indol-1-<14C>-one

Conditions	Yield
With methanesulfonic acid In various solvent(s) at 125℃; for 11h;	66%

2-mercapto-1-methylethylamine hydrochloride (4145-98-6) + 4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) → rac-1-<(5-Methylimidazol-4-yl)methylthio>-2-propyl-Dihydrobromid

Conditions	Yield
With hydrogen bromide for 6h; Heating;	65%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + 3-mercaptopropionic acid (107-96-0) → 3-(5-Methyl-1H-imidazol-4-ylmethylsulfanyl)-propionic acid (112528-38-8)

Conditions	Yield
In acetic acid for 24h; Heating;	54%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + p-toluenesulfonyl chloride (98-59-9) → 4-chloromethyl-5-methyl-1-(4-methylbenzenesulphonyl)-imidazole (155795-83-8) + 3-tosyl-4-chloromethyl-5-methyl-imidazole

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide Ambient temperature;	A 42% B n/a

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + (R)-1-Amino-propane-2-thiol; hydrochloride → (S)-2-<(5-Methylimidazol-4-yl)methylthio>-1-propyl-Dihydrobromid

Conditions	Yield
With hydrogen bromide for 6h; Heating;	40%

4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) + 2,3,4,5-tetrahydro-5-methyl-1H-pyrido[4,3-b]indol-1-one (122852-75-9) → alosetron (122852-42-0)

Conditions	Yield
In 1-methyl-pyrrolidin-2-one at 140℃; for 4h; Inert atmosphere;	29%

Ethyl bromodifluoroacetate (667-27-6) + 4-hydroxymethyl-5-methylimidazole hydrochloride (38585-62-5) → 3,3-Difluoro-4-(5-methyl-1H-imidazol-4-yl)-4-oxo-butyric acid ethyl ester

Conditions	Yield
With 1,4-dioxane; manganese(IV) oxide; phosphoric acid; trityl chloride; dimethyl sulfoxide; triethylamine; dicyclohexyl-carbodiimide; trifluoroacetic acid; zinc Yield given. Multistep reaction;

Upstream product

• 123-91-1 1,4-dioxane 
• 50-00-0 formaldehyd 
• 822-36-6 4-Methylimidazole 
• 67-63-0 isopropyl alcohol 
• 822-36-6 4-methyl-1H-imidazole 
• 73166-01-5 (4-methyl-imidazol-1-yl)-methanol 
• 51605-33-5 4-methyl-5-chloromethyl-imidazole hydrochloride 
• 51605-32-4 ethyl 4⁽⁵⁾-methylimidazole-5⁽⁴⁾-carboxylate 
• 60-29-7 diethyl ether 
• 51605-32-4 Ethyl 5-Methyl-4-imidazolecarboxylate 

Downstream Products

• 69395-89-7 5-methyl-4-chloromethyl imidazole 
• 1331755-54-4 4-(tert-butyldiphenylsilyloxymethyl)-5-methyl-1H-imidazole 
• 1331755-54-4 5-(tert-butyldiphenylsilyloxymethyl)-4-methyl-1H-imidazole 
• 1331755-57-7 5-(tert-butyldiphenylsilyloxymethyl)-4-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole 
• 1331755-56-6 4-(tert-butyldiphenylsilyloxymethyl)-5-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole 
• 1331755-58-8 1-[5-(tert-butyldiphenylsilyloxymethyl)-4-methyl-1-(2-(trimethylsilyl)ethoxymethyl)-1H-imidazol-2-yl]ethanone 
• 122852-42-0 alosetron 
• 38603-72-4 2-[((5-methyl-1H-imidazol-4-yl)methyl)thio]ethanamine dihydrochloride 
• 38603-72-4 4-Methyl-5-[(2-amino-ethyl)thiomethyl]-imidazole dihydrochloride 
• 58086-67-2 1-methyl-2-fluoropyridinium p-toluenesulfonate 
• 38585-67-0 4-methyl-5-<(2-aminoethyl)-thiomethyl>-imidazole 
• 38585-67-0 4-{[(2-aminoethyl)thio]methyl}-5-methylimidazole 
• 128486-54-4 6-fluoro-2,3,4,5-tetrahydro-5-methyl-2-[(5-methyl-1H-imidazol-4-yl)-methyl]-1H-pyrido[4,3-b]indol-1-one 
• 106147-84-6 4-Hydroxymethyl-5-methyl-1-(triphenylmethyl)imidazole 

Relevant articles and documents

Design, synthesis and evaluation of small molecule CD4-mimics as entry inhibitors possessing broad spectrum anti-HIV-1 activity

Since our first discovery of a CD4-mimic, NBD-556, which targets the Phe43 cavity of HIV-1 gp120, we and other groups made considerable progress in designing new CD4-mimics with viral entry-antagonist property. In our continued effort to make further progress we have synthesized twenty five new analogs based on our earlier reported viral entry antagonist, NBD-11021. These compounds were tested first in HIV-1 Env-pseudovirus based single-cycle infection assay as well as in a multi-cycle infection assay. Four of these new compounds showed much improved antiviral potency as well as cytotoxicity. We selected two of the best compounds 45A (NBD-14009) and 46A (NBD-14010) to test against a panel of 51 Env-pseudotyped HIV-1 representing diverse subtypes of clinical isolates. These compounds showed noticeable breadth of antiviral potency with IC50of as low as 150 nM. These compounds also inhibited cell-to-cell fusion and cell-to-cell HIV-1 transmission. The study is expected to pave the way of designing more potent and selective HIV-1 entry inhibitors targeted to the Phe43 cavity of HIV-1 gp120.

Process for the manufacture of 4-methyl-5-hydroxymethyl-imidazole

A process is provided for the manufacture of 4-lower-alkyl-5-hydroxymethyl-imidazole comprising reacting (4)-lower-alkyl imidazole with formaldehyde in an alkanol solvent having from 2 to 5 carbon atoms in the presence of a solid mild base suspended in the solvent.

Preparation of 5-hydroxymethylimidazoles

A process for the manufacture of 5-hydroxymethylimidazoles by reaction of an imidazole with formaldehyde or an oligomer of formaldehyde in aqueous hydrochloric acid solution containing from 5 to 18% by weight of hydrogen chloride, at from 80° to 160° C., if desired in a closed system under pressure, followed by isolation in the form of its hydrochloride of the 5-hydroxymethylimidazole obtained.