2016-36-6

Basic information

• Product Name: Choline salicylate
• Synonyms: (2-hydroxyethyl)trimethylammoniumsalicylate;2-hydroxy-n,n,n-trimethylethanaminiumsaltwith2-hydroxybenzoicacid(1:1);2-hydroxy-n,n,n-trimethyl-ethanaminiusaltwith2-hydroxybenzoicacid(1:;2-hydroxy-n,n,n-trimethyl-ethanaminiusaltwith2-hydroxybenzoicacid(1:1);actasal;arret;arthropan;artrobione
• CAS NO: 2016-36-6
• Molecular Formula: C₅H₁₄NO*C₇H₅O₃
• Molecular Weight: 241.28
• EINECS: 217-948-8
• Mol File: 2016-36-6.mol

Chemical Properties

• Melting Point: 49.5-50.0°
• Boiling Point: 384.06°C (rough estimate)
• Flash Point: 183 °C
• Appearance: Clear, colourless liquid
• Density: 1.1442 (rough estimate)
• Vapor Pressure: 4.45E-05mmHg at 25°C
• Refractive Index: 1.4596 (estimate)
• Storage Temp.: Hygroscopic, Refrigerator, under inert atmosphere
• Solubility: DMSO (Slightly), Methanol (Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: Choline salicylate(CAS DataBase Reference)
• NIST Chemistry Reference: Choline salicylate(2016-36-6)
• EPA Substance Registry System: Choline salicylate(2016-36-6)

Safety Data

• WGK Germany: 2
• RTECS: GA6475000
• F: 3-10
• Hazardous Substances Data: 2016-36-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Choline salicylate is used as a therapeutic agent for the treatment of Alzheimer's disease, providing protective effects against the neurodegenerative condition.
Used in Oral Health Applications:
Choline salicylate is used as a pain reliever for mouth ulcers, helping to alleviate the discomfort and pain associated with these oral sores.
Used in Pharmaceutical Formulations:
Choline salicylate is used as an active ingredient in the mint-flavored liquid formulation, Arthropan, which is designed to provide rapid absorption and higher salicylate plasma levels for effective pain relief and treatment of specific conditions.

Originator

Arthropan ,Purdue , US,1959

Manufacturing Process

A method of preparation is to react an acid salt of choline (such as choline chloride or choline bromide) with an alkaline salt of salicylic acid (such as sodium salicylate, potassium salicylate, or magnesium salicylate) in an alcoholic media.

Therapeutic Function

Analgesic; Antipyretic

Clinical Use

Choline salicylate has a lower incidence of GI side effects compared with aspirin, and it has been shown to be particularly useful in treating juvenile rheumatoid arthritis, in which aspirin was ineffective.

InChI:InChI=1/C7H6O3.C5H14NO/c8-6-4-2-1-3-5(6)7(9)10;1-6(2,3)4-5-7/h1-4,8H,(H,9,10);7H,4-5H2,1-3H3/q;+1/p-1

Synthetic route

cholin hydroxide (123-41-1) + salicylic acid (69-72-7) → choline salicylate (2016-36-6)

Conditions	Yield
In methanol at 20℃; for 12h;	100%
at 20 - 50℃; for 2h;	98%
With OH-	98%
In ethanol; water at 25℃;
In water at 20℃; for 12h;

choline chloride (67-48-1) + sodium salicylate (54-21-7) → choline salicylate (2016-36-6)

Conditions	Yield
In acetone for 72h;	100%
In ethanol at 20℃; for 1h;

choline chloride (67-48-1) → choline salicylate (2016-36-6)

Conditions	Yield
In acetone

Upstream product

• 67-48-1 choline chloride 
• 54-21-7 sodium salicylate 
• 123-41-1 cholin hydroxide 
• 69-72-7 salicylic acid 

Relevant articles and documents

Choline salicylate ionic liquid by X-ray scattering, vibrational spectroscopy and molecular dynamics

We report here a combined experimental and theoretical study on the bio-compatible salicylate choline ionic liquid. The liquid structure has been investigated by X-ray diffraction and vibrational (IR and Raman) spectroscopy. Local structure has been obtained from ab initio calculations on static ion pairs and from dynamic simulations of a small portion of the liquid. The theoretical models indicate that salicylate is connected by hydrogen bonding to choline mainly through the carboxylate group and forms stable ion pairs. A strong intramolecular interaction hinders internal rotations of the OH group of salicylate and competes with the hydrogen bonding with choline. When the liquid has been simulated by classical force fields we found a good agreement with the X-ray experimental features, comparable to that obtained from AIMD simulations. Important insights on hydrogen bonding between carboxylate and choline have been also derived from the analysis of the CO stretching modes of carboxylate measured in the Raman and IR spectra and calculated from VDOS-Wannier centers procedures.

Magnetic, Photo- And Electroluminescent: Multifunctional Ionic Tb Complexes

In the search for new multifunctional materials, particularly for application in solid-state lighting, a set of terbium salicylato (Sal) complexes of general composition [Cat][Tb(Sal)4] with the commonly ionic liquid-forming (IL) cations [Cat] = (2-hydroxyethyl)trimethylammonium (choline) (Chol+), diallyldimethylammonium (DADMA+), 1-ethyl-3-methylimidazolium (C2C1Im+), 1-butyl-3-methylimidazolium (C4C1Im+), 1-ethyl-3-vinylimidazolium (C2Vim+), and tetrabutylphosphonium (P4444+) were synthesized. All Tb compounds exhibit strong green photoluminescence of high color purity by energy transfer from the ligand in comparison with what the analogous La compounds show, and quantum yields can reach up to 63% upon ligand excitation. When excited with an HF generator, the compounds show strong green electroluminescence with the same features of mission. The findings promise a high potential of application as emitter materials in solid-state lighting. As an additional feature, the Tb compounds show a strong response to applied external fields, rendering them multifunctional materials.

Polyethylene glycol derivatization of the non-active ion in active pharmaceutical ingredient ionic liquids enhances transdermal delivery

We report the synthesis of four salts composed of the salicylate anion ([Sal]?) paired with tributylammonium ([HN444]+), choline ([Cho]+), 1-methylpyrrolidinium ([HMPyrr]+), and triethylene glycol monomethyl ether tributylammonium ([mPEG3N444]+) cations. Three of the synthesized salts (room temperature liquids [mPEG3N444][Sal] and [Cho][Sal], and a supercooled liquid [HN444][Sal]) belong to the category of ionic liquids (ILs), and one salt (solid [HMPyrr][Sal]) was a crystalline solid. ILs in their neat form were studied for membrane transport through a silicon membrane, and exhibited higher transport compared to a control experiment with sodium salicylate dissolved in mPEG3OH as solvent, but lower membrane transport compared to salicylic acid dissolved in mPEG3OH. The ‘PEGylated’ IL, [mPEG3N444][Sal], crossed the membrane with an ca. ～2.5-fold faster rate than that of any of the non-PEGylated ILs. This work demonstrates not only that API-ILs can eliminate the use of a solvent vehicle during application and notably transport through a membrane as opposed to a higher melting crystalline salt, but also that the membrane transport can be further enhanced by PEGylation of the counter ions.

Biofriendly ionic liquids for starch plasticization: A screening approach

A series of cholinium cation-based bioionic liquids (BioILs) were synthetized with the aim of screening their performance as potential plasticizers of thermoplastic starch. To synthesize these BioILs, two easy and fast synthetic routes were selected: an ion exchange reaction, direct and economical, and a two-step acid-base reaction. Most of these BioILs allowed efficient plasticization of starch by film casting. The structure of the anion used significantly influences the thermo(hygro)mechanical and recrystallization behavior, making it possible to modulate the properties of the final material.

Highly luminescent and color-tunable salicylate ionic liquids

High quantum yields of up to 40.5 % can be achieved in salicylate-bearing ionic liquids. A range of these ionic liquids have been synthesized and their photoluminescent properties studied in detail. The differences noted can be related back to the structure of the ionic liquid cation and possible interionic interactions. It is found that shifts of emission, particularly in the pyridinium-based ionic liquids, can be related to cation-anion pairing interactions. Facile and controlled emission color mixing is demonstrated through combining different ILs, with emission colors ranging from blue to yellow. Brilliant liquids: Highly photoluminescent salicylate ionic liquids (ILs) were synthesized and characterized. Quantum efficiencies up to 40.5 % were achieved. The optical properties are related to cation-anion pairing interactions. Facile controlled emission color mixing was demonstrated by combining different ILs, with emission colors ranging from blue to yellow (see figure).

DUAL FUNCTIONING IONIC LIQUIDS AND SALTS THEREOF

Disclosed herein are ionic liquid compositions comprising active pharmaceutical, biological, and nutritional compounds, and methods of use. Further disclosed are compositions of matter including liquid ion pairs alone or in solution and their use; compositions of ionic liquids that are 'solvated,' for example, 'hydrated' and their uses.

Biodegradable naphthenic acid ionic liquids: Synthesis, characterization, and quantitative structure-biodegradation relationship

It has been confirmed that commonly used ionic liquids are not easily biodegradable. When ultimately disposed of or accidentally released, they would accumulate in the environment, which strongly restricts largescale industrial applications of ionic liquids. Herein, ten biodegradable ionic liquids were prepared by a single, one-pot neutralization of choline and surrogate naphthenic acids. The structures of these naphthenic acid ionic liquids (NAILs) were characterized and confirmed by 1H and 13C NMR spectroscopy, IR spectroscopy, and elemental analysis, and their physical properties, such as densities, viscosities, conductivities, melting points (Tm), glass transition points (Tg), and the onset temperatures of decomposition (Td), were determined. More importantly, studies showed that these NAILs would be rapidly and completely biodegraded in aquatic environments under aerobic conditions, which would make them attractive candidates to be utilized in industrial processes. To explore the underlying mechanism involved in the NAIL biodegradation reaction and seek prediction of their biodegradability under environmental conditions, four molecular descriptors were chosen: the logarithm of the n-octanol/ water partition coefficient (log P), van der Waals volume (KvdW). energies of the highest occupied molecular orbital (EHOMO), and energies of the lowest unoccupied molecular orbital (ELUMO)-Through multiple linear regression, a general and qualified model including the biodegradation percentage for NAILs after the 28-day OECD 301D test (%B28) and molecular descriptors was developed. Regression analysis showed that the model was statistically significant at the 99 % confidence interval, thus indicating that the %B28 of NAILs could be explained well by the quantum chemical descriptor EHOMO, which might give some important clues in the discovery of biodegradable ionic liquids of other kinds.

Method for Producing Quaternary Ammonium Compounds

The present invention relates to a process for preparing quaternary ammonium compounds, which comprises reacting compounds comprising an sp3-hybridized nitrogen atom with a dialkyl sulfate or trialkyl phosphate and subjecting the resulting ammonium compound to an anion exchange.

METHOD FOR PRODUCING QUATERNARY AMMONIUM COMPOUNDS

The inventive method for producing quaternary ammonium compounds consists in reacting compounds containing an sp3 hybridised nitrogen atom with dialkyl sulphate or trialkyl phosphate and in exposing the thus obtained ammonium compound to an ion-exchange.

Hydrophilic choline salicylate formulation

Stable, solid formulations of choline salicylate and hydrophilic silicon dioxide, a process for their preparation and a method for their use.