60-31-1

Basic information

• Product Name: Acetylcholine chloride
• Synonyms: (2-Hydroxyethyl)trimethylammoniumchlorideacetate;2-(acetyloxy)-n,n,n-trimethyl-ethanaminiuchloride;acecholin;acetylcholinehydrochloride;acetylcholiniumchloride;achchloride;ammonium,(2-hydroxyethyl)trimethyl-,chloride,acetate;arterocoline
• CAS NO: 60-31-1
• Molecular Formula: C₇H₁₆NO₂*Cl
• Molecular Weight: 181.66
• EINECS: 200-468-8
• Product Categories: Ammonium Chlorides (Quaternary);Quaternary Ammonium Compounds;A-AM;Bioactive Small Molecules;Building Blocks;C6 to C7;Carbonyl Compounds;Cell Biology;Chemical Synthesis;Esters;Organic Building Blocks;Intermediates & Fine Chemicals;Pharmaceuticals;ACECOLINE
• Mol File: 60-31-1.mol

Chemical Properties

• Melting Point: 146-150 °C(lit.)
• Appearance: White/Crystalline Powder
• Density: 1.1235 (rough estimate)
• Refractive Index: 1.5560 (estimate)
• Storage Temp.: 0-6°C
• Solubility: H2O: 0.1 g/mL, clear, colorless
• Water Solubility: Soluble IN COLD WATER
• Sensitive: Hygroscopic
• Stability: Stable. Substances to be avoided include strong oxidizing agents. Protect from moisture - very hygroscopic.
• Merck: 14,87
• BRN: 3571875
• CAS DataBase Reference: Acetylcholine chloride(CAS DataBase Reference)
• NIST Chemistry Reference: Acetylcholine chloride(60-31-1)
• EPA Substance Registry System: Acetylcholine chloride(60-31-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39-36
• WGK Germany: 2
• RTECS: FZ9800000
• F: 3-8-10-21
• TSCA: Yes
• HazardClass: IRRITANT
• Hazardous Substances Data: 60-31-1(Hazardous Substances Data)

Usage

Uses

1. Used in Pharmaceutical Industry:
Acetylcholine chloride is used as a cholinergic agent for its ability to exert a powerful stimulant effect on the parasympathetic nervous system. It is also used as an antiarrhythmic, miotic, and vasodilator (peripheral) due to its various physiological effects.
2. Used in Neuromuscular Research:
Acetylcholine chloride is used as an endogenous neurotransmitter at cholinergic synapses for amplifying sarcolemma action potential, inducing muscle contractions, and studying the function of acetylcholine in various biological processes.
3. Used in Cardiology:
Acetylcholine chloride is used as a cardiac depressant for its negative chronotropic effect, which causes a decrease in heart rate, and its negative inotropic action on heart muscle, producing a decrease in the force of myocardial contractions.
4. Used in Pulmonary Research:
Acetylcholine chloride is used to increase alveolar fluid clearance in a dose-dependent manner and enhance Na+/K+-ATPase activity, effects which are blocked by atropine, in a mouse model of pulmonary edema.
5. Used in Protein Aggregation Research:
Acetylcholine chloride is used to inhibit peptide aggregation of p53 mutants in vitro at micromolar concentrations, providing insights into protein misfolding and aggregation-related diseases.

Biological Activity

Endogenous neurotransmitter. Acts at nicotinic and muscarinic acetylcholine receptors.

Biochem/physiol Actions

Acetylcholine chloride, injected at 20 mg/kg body weight, reduces mortality and plasma proinflammatory cytokines in mice with experimentally-induced sepsis . The cholinergic anti-inflammatory mechanism is probably mediated by interaction of acetylcholine with α7n cholinoreceptor on monocytes, macrophages, and neutrophils, which decreases the levels of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6.

Clinical Use

Atropine blocks the depressant effect of ACh on cardiacmuscle and its production of peripheral vasodilation (i.e.,muscarinic effects) but does not affect the skeletal musclecontraction (i.e., nicotinic effect) produced.ACh chloride is a hygroscopic powder that is available inan admixture with mannitol to be dissolved in sterile waterfor injection shortly before use. It is a short-acting mioticwhen introduced into the anterior chamber of the eye and isespecially useful after cataract surgery during the placementof sutures. When applied topically to the eye, it has littletherapeutic value because of poor corneal penetration andrapid hydrolysis by AChE.

Safety Profile

Poison by subcutaneous, intravenous, and parenteral routes. Moderately toxic by ingestion. When heated to decomposition it emits very toxic fumes of NOx, and Cl-. A cholinergic agent. See also CHOLINE ACETATE (ESTER).

Purification Methods

It is very soluble in H2O (>10%), and is very hygroscopic. If pasty, dry it in a vacuum desiccator over H2SO4 until a solid residue is obtained. Dissolve this in absolute EtOH, filter it and add dry Et2O, when the hydrochloride separates. Collect by filtration and store it under very dry conditions. [Jones & Major J Am Chem Soc 52 307 1930.] The chloroplatinate crystallises from hot H2O in yellow needles and can be recrystallised from 50% EtOH, m 242-244o [Dudley Biochem J 23 1069 1929]; other m given is 256-257o. The perchlorate crystallises from EtOH as prisms m 116-117o. [J Am Pharm Assocn 36 272 1947, Beilstein 4 IV 1446.]

InChI:InChI=1/C7H16NO2.ClH/c1-7(9)10-6-5-8(2,3)4;/h5-6H2,1-4H3;1H/q+1;/p-1

Synthetic route

choline chloride (67-48-1) + acetic anhydride (108-24-7) → acetylcholine chloride (60-31-1)

choline chloride (67-48-1) + acetyl chloride (75-36-5) → acetylcholine chloride (60-31-1)

trimethylamine (75-50-3) + <β-chloro-ethyl>-acetate → acetylcholine chloride (60-31-1)

Conditions	Yield
With benzene

choline chloride (67-48-1) + acetic acid (64-19-7) → acetylcholine chloride (60-31-1) + H2O

Conditions	Yield
With macrocyclic polyphenolate at 60℃; Equilibrium constant; pH 10.0; ionic strength 0.10 M; var. pH;

C29H38N6O4*C7H16NO2(1+)*Cl(1-) → acetylcholine chloride (60-31-1) + Trp-Aib-Gly-Leu-NHPh (232279-44-6)

Conditions	Yield
In chloroform-d1 at 24.84℃; Equilibrium constant; complex formation;

C31H42N6O4*C7H16NO2(1+)*Cl(1-) → acetylcholine chloride (60-31-1) + Trp-Aib-Gly-Leu-NH-C6H3(3,5-Me2) (271770-12-8)

Conditions	Yield
In chloroform-d1 at 24.84℃; Equilibrium constant; complex formation;

C32H32O4*C7H16NO2(1+)*Cl(1-) → acetylcholine chloride (60-31-1) + 2,11,20,29-tetraoxa[3.3.3.3]paracyclophane (143760-37-6)

Conditions	Yield
In chloroform-d1 at 22.85℃; Equilibrium constant;

C7H16NO2(1+)*C33H32N4O6*Cl(1-) → N-[N-(3-carboxypropanoyl)-tryptophyl]-1-benzyltryptophan + acetylcholine chloride (60-31-1)

Conditions	Yield
In water-d2 pH=7.4; Equilibrium constant; aq. buffer;

C7H16NO2(1+)*C40H38N4O6*Cl(1-) → N-[N-(3-carboxypropanoyl)-1-benzyltryptophyl]-1-benzyltryptophan + acetylcholine chloride (60-31-1)

Conditions	Yield
In water-d2 pH=7.4; Equilibrium constant; aq. buffer;

C7H16NO2(1+)*C23H24N2O5*Cl(1-) → N-(3-carboxypropanoyl)-1-benzyltryptophan + acetylcholine chloride (60-31-1)

Conditions	Yield
In water-d2 pH=7.4; Equilibrium constant; aq. buffer;

C7H16NO2(1+)*C28H32N4O5*Cl(1-) (852998-99-3) → acetylcholine chloride (60-31-1) + (S,S)-methyl 2-[2-tert-butoxycarbonylamino-3-(indol-3-yl)-propionylamino]-3-(indol-3-yl)propanoate (72254-56-9)

Conditions	Yield
In chloroform-d1 Equilibrium constant;

C7H16NO2(1+)*C35H38N4O5*Cl(1-) → methyl N-[N-(tert-butoxycarbonyltryptophyl)]-1-benzyltryptophanate (1256796-96-9) + acetylcholine chloride (60-31-1)

Conditions	Yield
In chloroform-d1 Equilibrium constant;

C7H16NO2(1+)*C42H44N4O5*Cl(1-) → methyl N-[N-(tert-butoxycarbonyl)-1-benzyltryptophyl]-1-benzyltryptophanate (1256796-97-0) + acetylcholine chloride (60-31-1)

Conditions	Yield
In chloroform-d1 Equilibrium constant;

acetylcholine chloride (60-31-1) → acetylcholine gibberallate

Conditions	Yield
In methanol at 25℃; for 0.5h;	97%

acetylcholine chloride (60-31-1) + sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate (79060-88-1) → 2-acetyloxy-N,N,N-trimethylethanaminium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate

Conditions	Yield
In methanol at 20℃; for 4h;	90%

sodium 1,2,3,4-tetracyano-5-((1R,3R,4S)-menthoxycarbonyl)cyclopentadienide + acetylcholine chloride (60-31-1) → C7H16NO2(1+)*C20H19N4O2(1-)

Conditions	Yield
In water Inert atmosphere;	88%

sodium 1,2,3,4-tetracyano-5-phenylcyclopentadienide + acetylcholine chloride (60-31-1) → C7H16NO2(1+)*C15H5N4(1-)

Conditions	Yield
In water Inert atmosphere;	78%

pentacyanocyclopentadienyl anion sodium salt + acetylcholine chloride (60-31-1) → C7H16NO2(1+)*C10N5(1-)

Conditions	Yield
In water Inert atmosphere;	73%

sodium 1,2,3,4-tetracyano-5-(ethoxycarbonyl)cyclopentadienide + acetylcholine chloride (60-31-1) → C7H16NO2(1+)*C12H5N4O2(1-)

Conditions	Yield
In water Inert atmosphere;	60%

indium(III) nitrate hydrate + acetylcholine chloride (60-31-1) + oxalic acid (144-62-7) → 2C2O4(2-)*In(3+)*C7H16NO2(1+)

Conditions	Yield
In ethanol; water at 120℃; for 120h;	56.8%

ethanol (64-17-5) + acetylcholine chloride (60-31-1) → choline chloride (67-48-1)

Conditions	Yield
beim Umkrystallisieren;

acetylcholine chloride (60-31-1) → choline chloride (67-48-1) + acetic acid (64-19-7)

Conditions	Yield
With macrocyclic polyphenolate; water at 60℃; Rate constant; Equilibrium constant; Mechanism; pH 10.0; ionic strength 0.10 M; var. pH;

acetylcholine chloride (60-31-1) + Trp-Aib-Gly-Leu-NHPh (232279-44-6) → C29H38N6O4*C7H16NO2(1+)*Cl(1-)

Conditions	Yield
In chloroform-d1 at 24.84℃; Equilibrium constant; complex formation;

acetylcholine chloride (60-31-1) + Trp-Aib-Gly-Leu-NH-C6H3(3,5-Me2) (271770-12-8) → C31H42N6O4*C7H16NO2(1+)*Cl(1-)

Conditions	Yield
In chloroform-d1 at 24.84℃; Equilibrium constant; complex formation;

acetylcholine chloride (60-31-1) + 2,11,20,29-tetraoxa[3.3.3.3]paracyclophane (143760-37-6) → C32H32O4*C7H16NO2(1+)*Cl(1-)

Conditions	Yield
In chloroform-d1 at 22.85℃; Equilibrium constant; Thermodynamic data; Further Variations:; Reaction partners;

acetylcholine chloride (60-31-1) + hexacyclohexanocucurbit[6]uril (868751-94-4, 406498-91-7) → C7H16NO2(1+)*C60H72N24O12*Cl(1-) (485368-99-8)

acetylcholine chloride (60-31-1) + tin(ll) chloride → 2Sn(2+)*(CH3)3NC2H4OC(O)CH3(1+)*5Cl(1-)=[CH3(O)COC2H4N(CH3)3]Sn2Cl5

Conditions	Yield
In neat (no solvent) heated ammonium salt and SnCl2 (1:2 molar ratio) to ca. 150°C in air; dried at 100°C overnight;

acetylcholine chloride (60-31-1) + tin(ll) chloride + zinc(II) chloride (7646-85-7) → Sn(2+)*Zn(2+)*(CH3)3NC2H4OH(1+)*5Cl(1-)=[HOC2H4N(CH3)3]ZnSnCl5

Conditions	Yield
In neat (no solvent) heated ammonium salt and metal chloride (1:1:1 molar ratio) to ca. 150°C in air; dried at 100°C overnight; MAS;

acetylcholine chloride (60-31-1) + zinc(II) chloride (7646-85-7) → 2Zn(2+)*(CH3)3NC2H4OC(O)CH3(1+)*5Cl(1-)=[CH3(O)COC2H4N(CH3)3]Zn2Cl5

Conditions	Yield
In neat (no solvent) heated ammonium salt and zinc chloride (1:2 molar ratio) to ca. 150°C in air; dried at 100°C overnight;

Cu(2+)*NH2CH(CH2C6H5)CO2(1-)*C12H8N2*NO3(1-)*2H2O=[Cu(NH2CH(CH2C6H5)CO2)(C12H8N2)(H2O)]NO3*H2O + acetylcholine chloride (60-31-1) → Cu(NH2CH(CH2C6H5)CO2)(C12H8N2)Cl*3H2O

Conditions	Yield
In water crystn. (room temp.), recrystn. (aq. MeOH);

C16H14N4*C42H42N28O14 + acetylcholine chloride (60-31-1) → 4-(4-aminophenylazo)naphthalen-1-amine (1095097-66-7) + C7H16NO2(1+)*C42H42N28O14*Cl(1-)

Conditions	Yield
pH=4.76; aq. acetate buffer;

sodium {[3-(5,6-dihydro-1,4,2-dioxazin-3-yl)pyridin-2-yl]sulfonyl}[(4,6-dimethoxypyrimidin-2-yl)carbamoyl]azanide + acetylcholine chloride (60-31-1) → 2-(acetyloxy)-N,N,N-trimethylethanaminium {[3-(5,6-dihydro-1,4,2-dioxazin-3-yl)pyridin-2-yl]sulfonyl}[(4,6-dimethoxypyrimidin-2-yl)carbamoyl]azanide (1187432-15-0)

Conditions	Yield
In methanol; water at 20℃; for 16h;

Upstream product

• 67-48-1 choline chloride 
• 108-24-7 acetic anhydride 
• 64-19-7 acetic acid 
• 75-36-5 acetyl chloride 
• 75-50-3 trimethylamine 
• 852998-99-3 C₇H₁₆NO₂⁽¹⁺⁾*C₂₈H₃₂N₄O₅*Cl^(1-) 

Downstream Products

• 67-48-1 choline chloride 
• 62-49-7 choline 
• 64-19-7 acetic acid 
• 1095097-66-7 4-(4-aminophenylazo)naphthalen-1-amine 

Relevant articles and documents

Catalytic application of zinc complex of oxygen depleted 1,3-bis(pyrazole)-p-tert-butylcalix[4]arene

In this paper we have described the synthesis and coordination properties of monometallic Zinc complex of oxygen depleted bis(pyrazole)-p-tert-butylcalix[4]arene ligand. We also present the catalytic activity of the Zinc–bis(pyrazole) complex, in acetylation of alcohols and lactide polymerization.

Modular incorporation of 1-benzyltryptophan into dipeptide hosts that bind acetylcholine in pure water

Proteins that recognize and bind quaternary ammonium ions depend on " aromatic-cage " structural motifs that use multiple aromatic residues to engage the side chain's ammonium cation. We introduce herein the use of 1-benzyltryp- tophan (Trp(Bn)) residues as synthetic, unnatural partial analogues of natural aromatic cages. We demonstrate the modular incorporation of these building blocks into simple dipeptide hosts and show that they are capable of binding quaternary ammonium ions in buffered water and in chloroform.

Cavitand templated catalysis of acetylcholine

A Zn-salen-modified cavitand templates the catalytic formation of acetylcholine from choline and acetic anhydride. The Royal Society of Chemistry 2006.

Binding of acetylcholine and tetramethylammonium to flexible cyclophane receptors: Improving on binding ability by optimizing host's geometry

The structure of a cyclophanic tetraester (1), previously employed for investigations on the cation-π interaction, has been optimized to better accommodate acetylcholine (ACh) and tetramethylammonium (TMA) guests. Following indications from molecular modeling calculations, a flexible cyclophane receptor of significantly improved binding properties has been obtained by removing the four carbonyl groups of the parent host. 2,11,20,29-Tetraoxa[3.3.3.3]paracyclophane (2) was prepared by an improved procedure, which was conveniently devised to avoid the formation of contiguous cyclooligomers that caused serious separation issues. Association of 2 with TMA picrate was measured in CDCl3 at T = 296 K by 1H NMR titrations and compared to binding data obtained for a set of reference hosts, including the parent tetraester 1, the corresponding cyclophanic tetraamine, the open-chain counterpart of 2, and its cyclooligomers from pentamer to octamer. Binding enhancements ranging from 15-fold (with respect to the tetraester and the tetraamine) to over 80-fold (with respect to the open-chain tetraether) were achieved by geometry optimization of the host. Binding of 2 to ACh and TMA was investigated for a variety of counterions. A constant binding free energy increment of nearly 8 kJ mol-1 with respect to 1 was observed, independent from the anion and irrespective of the different structure of the cationic guests. Results showed that the electrostatic inhibiting contribution of the counterion to the cation's binding is a characteristic constant of each anion. The value of -ΔG° = 44.9 kJ mol-1 extrapolated for TMA in the absence of a counterion indicates that 28-34 kJ mol-1 of binding free energy are lost in ion pairing.

Recognition of quaternary ammonium salts with tetrapeptides containing α-aminoisobutyric acid as a conformational constraint

Tetrapeptides Trp-Aib-Gly-Leu-NH-Ar (Aib:α-aminoisobutyric acid, 2-amino-2-methylpropanoic acid, Ar = phenyl or 3,5-dimethylphenyl) were synthesized. The peptides bound quaternary ammonium salts as guests in CDCl3. For every guest, the binding constant K of the peptide host which has a 3,5-dimethylphenyl group was larger than that of the host which has a phenyl group. ROESY analysis of the complex revealed that the N+-CH3 groups of the guests were close to the aromatic moieties of the host in the complex. The charge in cation guests, the φ-basicity of the host, and the turn conformation of the peptides were important factors for the complexation.