Neostigmine Methyl Sulfate Chemical Properties

Melting point:

175-177 °C(lit.)

storage temp. 

-20°C

solubility 

H₂O: 1 g/mL

form 

powder

color 

white

Water Solubility 

1g/10mL

Merck 

14,6464

InChI

InChI=1S/C12H19N2O2.CH4O4S/c1-13(2)12(15)16-11-8-6-7-10(9-11)14(3,4)5;1-5-6(2,3)4/h6-9H,1-5H3;1H3,(H,2,3,4)/q+1;/p-1

InChIKey

OSZNNLWOYWAHSS-UHFFFAOYSA-M

SMILES

C1(OC(=O)N(C)C)C=CC=C([N+](C)(C)C)C=1.S([O-])(=O)(=O)OC

CAS DataBase Reference

51-60-5(CAS DataBase Reference)

Safety Information

Hazard Codes 

T+

Risk Statements 

28-36/37/38-42/43-26/27/28

Safety Statements 

36-45-36/37/39-28A

RIDADR 

UN 2811 6.1/PG 2

WGK Germany 

3

RTECS 

CY1225000

HazardClass 

6.1(a)

PackingGroup 

II

HS Code 

29242990

Toxicity

LD50 in mice (mg/kg): 0.16 i.v.; 0.42 s.c.; 7.5 orally, (Randall, Lehmann)

MSDS

• Language:English Provider:3-[[(Dimethylamino)carbonyl]oxy]-N,N,N-trimethylbenzenaminium methyl sulfate
• Language:English Provider:ACROS
• Language:English Provider:SigmaAldrich

Neostigmine Methyl Sulfate Usage And Synthesis

Description

Neostigmine is a reversible inhibitor of acetylcholinesterase (AChE; K_d = 260 μM). In a rat model of knee joint inflammation, intrathecal administration of neostigmine (2-30 μg) increases endogenous acetylcholine levels and dose-dependently increases the latency of paw withdrawal in response to thermal and mechanical stimuli (ED₅₀s = 6.6 and 3.5 μg, respectively). Neostigmine (5 μg, i.p.) restores muscle action potentials in mice with a thymopoietin-induced neuromuscular block. Formulations containing neostigmine have been used in the treatment of myasthenia gravis and Ogilvie syndrome.

Chemical Properties

Crystalline Solid

Uses

Cholinergic; miotic; antidote (curare)

Definition

ChEBI: Neostigmine methyl sulfate is an arylammonium sulfate salt. It has a role as an EC 3.1.1.8 (cholinesterase) inhibitor.

brand name

Prostigmine (ICN).

General Description

Neostigmine methylsulfate,(m-hydroxyphenyl)trimethylammonium methylsulfatedimethylcarbamate or the dimethylcarbamic ester of 3-hydroxyphenyltrimethylammoniummethylsulfate (Prostigminmethylsulfate), is a bitter, odorless, white, crystalline powder.It is very soluble in water and soluble in alcohol. Solutionsare stable and can be sterilized by boiling. The compound istoo hygroscopic for use in a solid form and thus is alwaysused as an injection. Aqueous solutions are neutral to litmus.

Clinical Use

The methylsulfate salt is used postoperatively as a urinarystimulant and in the diagnosis and treatment of myastheniagravis.

Synthesis

Example 9 Preparation of neostigmine methyl sulfate (general procedure) To a 250 mL four-necked round-bottomed flask was added 3-(dimethylamino)phenyldimethylcarbamate and acetone obtained in Example 1. Dimethyl sulfate (1.66 eq.) was added dropwise to the flask at room temperature. The reaction mixture was stirred overnight and then cooled to 5 °C to 10 °C and kept for 2 hours. This was followed by filtration and the filtrate was washed with isopropanol. The residue was dried under vacuum at room temperature to give the crude product neostigmine methyl sulfate. Purification was carried out by recrystallization from isopropanol. Yield: 85%. Properties: light yellow oil HPLC Purity: 99.21%.

Purification Methods

Crystallise the sulfate from EtOH or Me2CO (m 143-144o). Its solubility in H2O is ~10%. [Beilstein 13 III 939.] (It is cholinergic and highly TOXIC.)

References

[1] Patent: WO2012/131699, 2012, A1. Location in patent: Page/Page column 15
[2] Pharmazie, 2001, vol. 56, # 2, p. 181 - 182
[3] Zhurnal Prikladnoi Khimii (Sankt-Peterburg, Russian Federation), 1941, vol. 14, p. 524,526
[4] Chem.Abstr., 1942, p. 3159
[5] Patent: CH208883, 1938,

Neostigmine Methyl Sulfate(51-60-5)Related Product Information

• Ammonium bisulfite
• Tetramethylammonium hydroxide pentahydrate
• PHENYLTRIMETHYLAMMONIUM METHOSULFATE
• DIMETHYLAMMONIUM DIMETHYLCARBAMATE(DIMCARB)
• AMMONIUM CARBAMATE
• 3-METHOXY-N-METHYLANILINE
• Neostigmine Methyl Sulfate
• Ammonium sulfate
• Sulfuric acid
• Ammonium bisulfate
• 3-Dimethylaminophenol
• Tetramethylammonium hydrogen sulfate
• 3-dimethylaminophenyl dimethylcarbamate
• 3-Dimethylaminoanisole
• PHENYLTRIMETHYLAMMONIUM HYDROXIDE
• 3-AMINOPHENYL N,N-DIMETHYLCARBAMATE, 97
• Phenyl carbamate
• Ammonium Sulfite