56610-81-2

Basic information

• Product Name: 2-(5-Mercaptotetrazole-1-yl)ethanol
• Synonyms: 2-(5-MERCAPTO-TETRAZOL-1-YL)-ETHANOL;2-(5-MERCAPTOTETRAZOLE-1-YL)ETHANOL;1-HYDROXY-5-MERCAPTO-1H-TETRAZOLE;1-HYDROXYETHYL-1H-TETRAZOLE-5-THIOL;1-HYDROXYETHYL-5-MERCAPTO-1H-TETRAZOLE;1-(2-HYDROXYETHYL)-5-MERCAPTO-1,2,3,4-TETRAZOLE;5-BENZYLMERCAPTO-1H-TETRAZOLE;5-BENZYLMERCAPTOTETRAZOLE
• CAS NO: 56610-81-2
• Molecular Formula: C₃H₆N₄OS
• Molecular Weight: 146.17
• EINECS: 1806241-263-5
• Product Categories: Tetrazoles
• Mol File: 56610-81-2.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 221.4 °C at 760 mmHg
• Flash Point: 2 °C
• Appearance: white crystals or crystalline powder
• Density: 1.76 g/cm³
• Vapor Pressure: 0.0222mmHg at 25°C
• Refractive Index: n20/D 1.354
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 14.20±0.10(Predicted)
• CAS DataBase Reference: 2-(5-Mercaptotetrazole-1-yl)ethanol(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(5-Mercaptotetrazole-1-yl)ethanol(56610-81-2)
• EPA Substance Registry System: 2-(5-Mercaptotetrazole-1-yl)ethanol(56610-81-2)

Safety Data

• Hazard Codes: F,Xn,Xi,T
• Statements: 11-20/21/22-36-36/37/38-23/24/25
• Safety Statements: 26-36-45-36/37/39-36/37-16
• RIDADR: UN 1648 3/PG 2
• WGK Germany: 3
• Hazardous Substances Data: 56610-81-2(Hazardous Substances Data)

Usage

Description

2-(5-Mercaptotetrazole-1-yl)ethanol is a white crystalline mercaptotetrazole derivative known for its significant role in the pharmaceutical industry. It is characterized by its unique chemical structure, which contributes to its various applications and properties.

Uses

Used in Pharmaceutical Industry:
2-(5-Mercaptotetrazole-1-yl)ethanol is used as an intermediate in the preparation of the beta-lactam antibiotic Flomoxef (F401850). Its role in the synthesis process is crucial for the development of this antibiotic, which is utilized for treating various bacterial infections.
Additionally, 2-(5-Mercaptotetrazole-1-yl)ethanol is used as a metabolite of Flomoxef, further emphasizing its importance in the pharmaceutical sector.
Used in Enzyme Inhibition:
2-(5-Mercaptotetrazole-1-yl)ethanol also exhibits vitamin K-dependent glutamylcarboxylase inhibitory activity. This property makes it a potential candidate for applications in the field of enzyme inhibition, which can be beneficial in various therapeutic approaches and drug development processes.

InChI:InChI=1/C3H6N4OS/c8-2-1-7-3(9)4-5-6-7/h8H,1-2H2,(H,4,6,9)

Synthetic route

C6H10Cl2N2O2S2 → 1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2)

Conditions	Yield
With sodium azide In water; isopropyl alcohol at 25 - 50℃; for 3h;	95%

(2-hydroxy-ethyl)-dithiocarbamic acid methyl ester (56158-48-6) → 1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2)

Conditions	Yield
With sodium azide In ethanol at 70℃; for 3h; Cyclization;
In 1,4-dioxane; water

3N-hydrochloric acid + 1-(2-t-butoxyethyl)-1H-tetrazole-5-thiol → 1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2)

Conditions	Yield
aluminium trichloride In dichloromethane; ethyl acetate; methoxybenzene

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + 7-methoxy-7-(N-tert-butoxycarbonyl)-3-(chloromethyl)-8-oxo-5-oxo-1-azabicyclo[4.2.0]-2-ene-2-carboxylic acid diphenylmethyl ester → 7-methoxy-7-(Ν-tert-butoxycarbonyl)-3-(((1-(2-hydroxyethyl)-1Η-tetrazol-5-yl)mercapto)methyl)-8-oxo-5-oxo-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate diphenylmethyl ester

Conditions	Yield
With sodium hydrogencarbonate In N,N-dimethyl-formamide at 25℃; for 3h; Temperature;	95%

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + 7-Aminocephalosporanic acid (957-68-6) → (6R,7R)-7-Amino-3-[1-(2-hydroxy-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (55817-46-4)

Conditions	Yield
With boron trifluoride In acetonitrile at 30℃; for 1.5h;	89%

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + N-[4-(4-piperidinomethyl-pyridin-2-yloxy)-cis-2-butenyl]-4-chlorobutyramide → N-[4-(4-Piperidinomethyl-pyridin-2-yloxy)-cis-2-butenyl]-4-[1-(2-hydroxyethyl)tetrazol-5-ylthio]butyramide

Conditions	Yield
	63%

methanol (67-56-1) + 1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + nickel(II) acetate tetrahydrate (6018-89-9) + triethylamine (121-44-8) → 12C3H5N4OS(1-)*8CH3O(1-)*9Ni(2+)*2C8H20N(1+)

Conditions	Yield
at 120℃; for 72h; Autoclave;	55%

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) → C6H10N8O2S2

Conditions	Yield
With dihydrogen peroxide; sodium iodide In water at 20℃; for 2.5h;	50%

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + nickel(II) acetate tetrahydrate (6018-89-9) → C18H36N24Ni3O12S6(6-)*4H2O*6H(1+)

Conditions	Yield
In methanol; chloroform at 65℃; for 5h;	50%

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + copper(I) bromide (7787-70-4) → 4Cu(1+)*3C3H5N4OS(1-)*Br(1-)

Conditions	Yield
In methanol; ethanol at 120℃; for 72.5h; Sealed tube;	40%

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) → 5,6-dihydrothiazolo[3.2-d]tetrazole

Conditions	Yield
With azodicarboxylic acid bis(2-methoxyethyl) ester; triphenylphosphine In tetrahydrofuran at 20℃; Mitsunobu reaction;	32%

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + copper diacetate (142-71-2) → Cu(1+)*C3H5N4OS(1-)

Conditions	Yield
In methanol; ethanol at 120℃; for 72.5h; Sealed tube;	22%

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + copper(II) choride dihydrate → 2Cu(1+)*C3H5N4OS(1-)*Cl(1-)

Conditions	Yield
In methanol; ethanol at 120℃; for 72.5h; Sealed tube;	18%

copper(l) iodide (7681-65-4) + 1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) → 4Cu(1+)*3C3H5N4OS(1-)*I(1-)

Conditions	Yield
In ethanol; water at 120℃; for 72.5h; Sealed tube;	12%

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + (6R)-3-acetoxymethyl-7t-[2-(2-amino-thiazol-4-yl)-acetylamino]-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (58233-18-4) → (6R)-7t-[2-(2-amino-thiazol-4-yl)-acetylamino]-3-[1-(2-hydroxy-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (119672-56-9)

Conditions	Yield
With sodium hydrogencarbonate

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + p-Methoxybenzyl (1S,5R,6S)-2-Hydroxymethyl-1-methyl-6-<(R)-1-trinthylsilyloxyethyl>carbapen-2-em-3-carboxylate (135271-52-2) → (4S,5R,6S)-3-[1-(2-Hydroxy-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-4-methyl-7-oxo-6-((R)-1-triethylsilanyloxy-ethyl)-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-methoxy-benzyl ester

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran Ambient temperature;

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + pivaloyloxymethyl (3S*,4R*)-α-<4-(2,3-epoxypropyl)-3-(4-methyl-2-oxo-1,3-dioxolan-4-yl)-2-azetidinone-1-yl>-α-triphenylphosphoranilideneacetate (102990-88-5, 103065-48-1) → 2,2-Dimethyl-propionic acid 2-[(2R,3S)-2-{2-hydroxy-3-[1-(2-hydroxy-ethyl)-1H-tetrazol-5-ylsulfanyl]-propyl}-3-((S)-4-methyl-2-oxo-[1,3]dioxolan-4-yl)-4-oxo-azetidin-1-yl]-2-(triphenyl-λ5-phosphanylidene)-acetoxymethyl ester

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane Ambient temperature;

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + (6S,7S)-3-Bromomethyl-7-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-8-oxo-4-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (157731-85-6) → (6S,7S)-7-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-[1-(2-hydroxy-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-8-oxo-4-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (136278-83-6)

Conditions	Yield
With sodium hydrogencarbonate In acetone for 2h; Ambient temperature;

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + (2S,4S)-4-Acetylsulfanyl-2-iodomethyl-pyrrolidine-1-carboxylic acid allyl ester (288399-99-5) → (2S,4S)-4-Acetylsulfanyl-2-[1-(2-hydroxy-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-pyrrolidine-1-carboxylic acid allyl ester (288400-18-0)

Conditions	Yield
With potassium carbonate In acetone at 60℃; for 3h; Alkylation;

1-(2-hydroxyethyl)-5-mercapto-1H-tetrazole (56610-81-2) + 2-benzhydryloxycarbonyl-7-tert-butoxycarbonylamino-3-(2-dimethylamino-vinyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene + 2-benzhydryloxycarbonyl-7-[2-methoxyimino-2-(2-tritylamino-thiazol-4-yl)-acetamido]-8-oxo-3-(2-tosyloxy-vinyl)-5-thia-1-aza-bicyclo[4.2.0]-oct-2-ene + N-ethyl-N,N-diisopropylamine (7087-68-5) → 2-Benzhydryloxycarbonyl-3-{2-[1-(2-hydroxyethyl)tetrazol-5-yl]-thiovinyl}-7-[2-methoxyimino-2-(2-tritylamino-thiazol-4-yl)-acetamido]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene

Conditions	Yield
In N-methyl-acetamide; dichloromethane; cyclohexane; ethyl acetate

Upstream product

• 56158-48-6 (2-hydroxy-ethyl)-dithiocarbamic acid methyl ester 

Downstream Products

• 136278-83-6 (6S,7S)-7-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-[1-(2-hydroxy-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-8-oxo-4-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 

Relevant articles and documents

Preparation method of 5-mercapto-1H-tetrazole compound

The invention relates to a preparation method of a 5-mercapto-1H-tetrazole compound shown in a formula (III), which comprises the following steps of: (1) dissolving disulfide in halogenated alkane, dropwise adding a chlorinating reagent at -5 to 0 DEG C, carrying out heat preservation reaction for 2-5 hours, and carrying out reduced pressure distillation at 5-10 DEG C to obtain chlorinated disulfide; (2) dissolving the chlorinated disulfide prepared in the step (1) in lower saturated monohydric alcohol, dissolving sodium azide in water, dripping a sodium azide solution at 20-30 DEG C, heatingto 50-65 DEG C after dripping, and carrying out heat preservation reaction for 2-5 hours; (3) evaporating the solution obtained in the step (2) at 40-45 DEG C under reduced pressure to remove the lower saturated monohydric alcohol, and adding halogenated alkane for extraction for three times to obtain a halogenated alkane extraction liquid; (4) concentrating and crystallizing the halogenated alkane extraction liquid prepared in the step (3), and filtering to obtain the 5-mercapto-1H-tetrazole compound. The preparation method has high yield, good product quality, convenient solvent recycling and low production cost.

Synthesis of hydroxyethyltetrazolethiol and etherified intermediates therefor

By heating an N-(2-hydroxyethyl)dithiocarbamate ester protected at its hydroxy group as an ether in the presence of an azide, the corresponding 1-(protected hydroxyethyl)-1H-tetrazole-5-thiol is obtained, and then, if required, deprotecting the etheric protection to give an industrially useful chemical, 1-(2-hydroxyethyl)-1H-tetrazole-5-thiol.

7-Substituted-3-aminoalkyl-, acylaminoalkyl-, or hydroxyalkyl-substituted heterocyclic thiomethyl-3-cephem-4-carboxylic acid derivatives and preparation thereof

Cephalosporanic acid derivatives and preparation thereof having the following formula STR1 wherein R1 is hydrogen or acyl, and R2 is aminoalkyl-, acylaminoalkyl-, sulfoalkylaminoalkyl-, or hydroxyalkyl-substituted, N- or N and S-containing heterocyclic groups.