Acetylcholine Chloride

Acetylcholine Chloride
2-acetyloxyethyl(trimethyl)azanium;chloride
60-31-1

Molecular Formula:	C7H16ClNO2
Molecular Weight:	181.66 g/mol

Acetylcholine chloride is obtained as white or off-white hygroscopic crystals, or as a crystalline powder. The salt is odorless, or nearly odorless, and is a very deliquescent powder. Acetylcholine bromide is obtained as deliquescent crystals, or as a white crystalline powder. The substance is hydrolyzed by hot water and alkali

Acetylcholine is an organic chemical that functions in the brain and body of many types of animals, including humans, as a neurotransmitter—a chemical released by nerve cells to send signals to other cells. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic. Substances that interfere with acetylcholine activity are called anticholinergics.

Acetylcholine is the neurotransmitter used at the neuromuscular junction—in other words, it is the chemical that motor neurons of the nervous system release in order to activate muscles. This property means that drugs that affect cholinergic systems can have very dangerous effects ranging from paralysis to convulsions. Acetylcholine is also used as a neurotransmitter in the autonomic nervous system, both as an internal transmitter for the sympathetic nervous system and as the final product released by the parasympathetic nervous system.

Inside the brain, acetylcholine functions as a neuromodulator—a chemical that alters the way other brain structures process information rather than a chemical used to transmit information from point to point. The brain contains a number of cholinergic areas, each with distinct functions. They play an important role in arousal, attention, and motivation.

Partly because of its muscle-activating function, but also because of its functions in the autonomic nervous system and brain, a large number of important drugs exert their effects by altering cholinergic transmission. Numerous venoms and toxins produced by plants, animals, and bacteria, as well as chemical nerve agents such as Sarin, cause harm by inactivating or hyperactivating muscles via their influences on the neuromuscular junction. Drugs that act on muscarinic acetylcholine receptors, such as atropine, can be poisonous in large quantities, but in smaller doses they are commonly used to treat certain heart conditions and eye problems. Scopolamine, which acts mainly on muscarinic receptors in the brain, can cause delirium and amnesia. The addictive qualities of nicotine derive from its effects on nicotinic acetylcholine receptors in the brain.

Chemistry

Acetylcholine is a choline molecule that has been acetylated at the oxygen atom. Because of the presence of a highly polar, charged ammonium group, acetylcholine does not penetrate lipid membranes. Because of this, when the drug is introduced externally, it remains in the extracellular space and does not pass through the blood–brain barrier. A synonym of this drug is miochol.

History

Acetylcholine (ACh) was first identified in 1915 by Henry Hallett Dale for its actions on heart tissue. It was confirmed as a neurotransmitter by Otto Loewi, who initially gave it the name Vagusstoff because it was released from the vagus nerve. Both received the 1936 Nobel Prize in Physiology or Medicine for their work. Acetylcholine was also the first neurotransmitter to be identified.

CLIP

http://drugsynthesis.blogspot.in/2011/11/laboratory-synthesis-of-acetylcholine.html

Laboratory Synthesis Of Acetylcholine chloride

Acetylcholine chloride Chemical Name: 2- (acetyl oxy)- N ,N ,N- tri methyl ethan aminium chloride
Acetylcholine chloride Use: parasympathomimetic, miotic, vasodilator (peripheral)
Acetylcholine chloride MW: 181.66
Acetylcholine chloride MF: C7H16ClNO2
Acetylcholine chloride LD50: 10 mg/kg (M, i.v.); 3 g/kg (M, p.o.);
22 mg/kg (R, i.v.); 2500 mg/kg (R, p.o.)
Reference(s):

1. Baeyer, A. v.: Justus Liebigs Ann. Chem. (JLACBF) 142, 235 (1867).
2. Nothnagel: Arch. Pharm. (Weinheim, Ger.) (ARPMAS) 232, 265 (1894).
3. Fourneau, E.; Page, H.J.: Bull. Soc. Chim. Fr. (BSCFAS) [4] 15, 544 (1914).
4. DE 801 210 (BASF; appl. 1948).
5. US 1 957 443 (Merck & Co.; 1934; appl. 1931).
6. US 2 012 268 (Merck & Co.; 1935; appl. 1931).
7. US 2 013 536 (Merck & Co.; 1935; appl. 1931).

Acetylcholine
IUPAC name	2-Acetoxy-N,N,N-trimethylethanaminium
Abbreviation	ACh
Sources	motor neurons, parasympathetic nervous system, brain
Targets	skeletal muscles, brain, many other organs
Receptors	nicotinic, muscarinic
Agonists	nicotine, muscarine, cholinesterase inhibitors
Antagonists	tubocurarine, atropine
Precursor	choline, acetyl-CoA
Synthesizing enzyme	choline acetyltransferase
Metabolizing enzyme	acetylcholinesterase
Database links
CAS Number	51-84-3
PubChem	CID: 187
IUPHAR/BPS	294
DrugBank	EXPT00412
ChemSpider	182
KEGG	C01996

1H NMR PREDICT

13 C NMR PREDICT

/////////CC(=O)OCC[N+](C)(C)C.[Cl-]

 
VALSARTAN

mp 114–118 °C; 

¹H NMR (400 MHz, DMSO-d₆): δ 12.6 (brs, 1H), 7.72 (m, 4H), 7.24 (m, 1H), 7.15 (m, 2H), 6.94 (m, 1H), 4.58 (m, 1H), 4.40 (m, 1H), 3.33 (m, 1H), 2.25 (m, 1H), 1.52 (m, 6H), 0.9 (m, 3H), 0.84 (m, 3H), 0.74 (m, 3H); 


¹³C NMR (100 MHz, DMSO-d₆): δ 174.0, 172.4, 171.8, 141.7, 138.2, 131.54, 131.1, 131.0, 129.3,128.8, 128.2, 127.4, 126.7, 70.3, 63.4, 49.9, 32.9, 28.05, 27.3, 22.2, 20.6, 14.2; 

ESIMS: m/z calcd [M]⁺: 435; found: 436 [M+H]⁺; HRMS (ESI): m/z calcd [M]⁺: 435.5187; found: 435.5125 [M]<sup>+




US 7439261 B2
1H-NMR (CDCl₃) (0.80-1.15 (m, 9H); 1.20-1.50 (m, 2H); 1.60-1.80 (m, 2H); 2.60 (t, 2H); 2.65-2.80 (m, 2H), 3.70 (d, 1H), 4.10 (d, 0.3 H), 4.30 (d, 0.7 H), 4.90 (d, 0.7H), 5.2 (d, 0.3H); 7.00 (d, 0.3H); 7.10-7.20 (m, 4H), 7.40-7.60 (m, 3H), 7.85 (d, 0.7 H).



SHORT DESCRIPTION</sup>

Valsartan, N-(1-oxopentyl)-N-[[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-L-valine, is a known anti-hypertensive agent having the following formula (I):

Valsartan and its preparation are disclosed in U.S. Pat. No. 5,399,578, in particular in Example 16. One of the synthetic routes according to U.S. Pat. No. 5,399,578 can be schematically represented as follows:

The synthetic pathway comprises various steps, among which:

• • coupling of compound (3) with 2-chlorobenzonitrile to obtain compound (4),
  • radicalic bromination of compound (4) to give compound (5),
  • transformation of the brominated derivative (5) into the respective aldehyde derivative (6),
  • reductive alkylation of compound (6) to obtain intermediate (8),
  • acylation of compound (8) to obtain intermediate (9),
  • conversion of the cyano group to the tetrazole group to afford intermediate (10),
  • deprotection of the carboxylic group by hydrogenolysis to obtain valsartan.

• It is marketed as the free acid under the name DIOVAN. DIOVAN is prescribed as oral tablets in dosages of 40 mg, 80 mg, 160 mg and 320 mg ofvalsartan.
• [0004]
  Valsartan and/or its intermediates are disclosed in various references, including: U.S. Pat. Nos. 5,399,578 ,5,965,592 , 5,260,325 , 6,271,375 , WO 02/006253 , WO 01/082858 , WO 99/67231 , WO 97/30036 , Peter Bühlmayer, et. al., Bioorgan. & Med. Chem. Let., 4(1) 29-34 (1994), Th. Moenius, et. al., J. Labelled Cpd. Radiopharm., 43(13) 1245 - 1252 (2000), and Qingzhong Jia, et. al., Zhongguo Yiyao Gongye Zazhi, 32(9) 385-387 (2001), all of which are incorporated herein by reference.
• [0005]
  Valsartan is an orally active specific angiotensin II antagonist acting on the AT1 receptor subtype. Valsartan is prescribed for the treatment of hypertension. U.S. Pat. No. 6,395,728 is directed to use of valsartan for treatment of diabetes related hypertension. U.S. Pat. Nos. 6,465,502 and 6,485,745 are directed to treatment of lung cancer with valsartan. U.S. Pat. No. 6,294,197 is directed to solid oral dosage forms of valsartan

GOOD ARTICLES

http://users.uoa.gr/~tmavrom/2009/valsartan2009.pdf

http://www.acgpubs.org/JCM/2009/Volume%203/Issue%201/JCM-0908-14.pdf

https://www.beilstein-journals.org/bjoc/single/printArticle.htm?publicId=1860-5397-6-27 REPORTS
 mp 114–118 °C; ¹H NMR (400 MHz, DMSO-d₆): δ 12.6 (brs, 1H), 7.72 (m, 4H), 7.24 (m, 1H), 7.15 (m, 2H), 6.94 (m, 1H), 4.58 (m, 1H), 4.40 (m, 1H), 3.33 (m, 1H), 2.25 (m, 1H), 1.52 (m, 6H), 0.9 (m, 3H), 0.84 (m, 3H), 0.74 (m, 3H); ¹³C NMR (100 MHz, DMSO-d₆): δ 174.0, 172.4, 171.8, 141.7, 138.2, 131.54, 131.1, 131.0, 129.3,128.8, 128.2, 127.4, 126.7, 70.3, 63.4, 49.9, 32.9, 28.05, 27.3, 22.2, 20.6, 14.2; ESIMS: m/z calcd [M]⁺: 435; found: 436 [M+H]⁺; HRMS (ESI): m/z calcd [M]⁺: 435.5187; found: 435.5125 [M]⁺

Valsartan 

Structural formula

UV - Spectrum

Conditions : Concentration - 1 mg / 100 ml
The solvent designation schedule	methanol	water	0.1М HCl	0.1M NaOH
maximum absorption	249 nm	250 nm	248 nm	251 nm
	309	302	289	311
e	13400	13100	12600	13500

IR - spectrum

Wavelength (μm)
Wave number (cm -1 )

NMR spectrum

references

• UV and IR Spectra. H.-W. Dibbern, R.M. Muller, E. Wirbitzki, 2002 ECV
• NIST/EPA/NIH Mass Spectral Library 2008
• Handbook of Organic Compounds. NIR, IR, Raman, and UV-Vis Spectra Featuring Polymers and Surfactants, Jr., Jerry Workman. Academic Press, 2000.
• Handbook of ultraviolet and visible absorption spectra of organic compounds, K. Hirayama. Plenum Press Data Division, 1967.

<sup>CLIP





Scheme 2: (a) Et3N, CH2Cl2, 0 °C, 95%; (b) NaH, THF, 70%; (c) n-BuLi, 25 °C, THF, anhyd ZnCl2, −20 °C, Q-phos, Pd(OAc)2, 75 °C, 2 h, 80%; (d) 3 N NaOH, MeOH, reflux, 90%.

http://www.beilstein-journals.org/bjoc/single/articleFullText.htm?publicId=1860-5397-6-27

valsartan 8; mp 114–118 °C; 1H NMR (400 MHz, DMSO-d6): δ 12.6 (brs, 1H), 7.72 (m, 4H), 7.24 (m, 1H), 7.15 (m, 2H), 6.94 (m, 1H), 4.58 (m, 1H), 4.40 (m, 1H), 3.33 (m, 1H), 2.25 (m, 1H), 1.52 (m, 6H), 0.9 (m, 3H), 0.84 (m, 3H), 0.74 (m, 3H); 13C NMR (100 MHz, DMSO-d6): δ 174.0, 172.4, 171.8, 141.7, 138.2, 131.54, 131.1, 131.0, 129.3,128.8, 128.2, 127.4, 126.7, 70.3, 63.4, 49.9, 32.9, 28.05, 27.3, 22.2, 20.6, 14.2; ESIMS: m/z calcd [M]+: 435; found: 436 [M+H]+; HRMS (ESI): m/z calcd [M]+: 435.5187; found: 435.5125 [M]+












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(E)-2-(fluoro(phenyl)methylene)cyclopentan-1-one

Silver-initiated radical ring expansion/fluorination of ethynyl cyclobutanols: efficient synthesis of monofluoroethenyl cyclopentanones

Green Chem., 2016, Advance Article
DOI: 10.1039/C6GC02656G, Communication

Qingshan Tian, Bin Chen, Guozhu Zhang
A stereoselective synthesis of [small beta]-halogenated 2-methylenecyclopentanones via silver-catalyzed formal ring expansion using water as the cosolvent is described.

Silver-initiated radical ring expansion/fluorination of ethynyl cyclobutanols: efficient synthesis of monofluoroethenyl cyclopentanones

Qingshan Tian,^a   Bin Chen^a and   Guozhu Zhang*^a  

*

Corresponding authors

^a

State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China
E-mail: guozhuzhang@sioc.ac.cn

Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC02656G

A stereoselective synthesis of β-halogenated 2-methylenecyclopentanones via silver-catalyzed formal ring expansion using water as the cosolvent is described. A variety of 2-methylenecyclopentanones with fluoro, chloro and bromo functionalities are efficiently prepared from 1-alkynyl cyclobutanols. This method offers facile access to halogenated complex molecules which are not only useful chemicals but also valuable building blocks for further derivatizations.

1-(m-tolylethynyl)cyclobutan-1-ol (1b) Yield: 89%; Yellow oil;

1H NMR (400 MHz, CDCl3)

δ 7.25 (s, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.18 (t, J = 7.5 Hz, 1H), 7.10 (d, J = 7.5 Hz, 1H), 2.51 (dt, J = 15.8, 6.3 Hz, 2H), 2.34 (t, J = 9.3 Hz, 2H), 2.30 (s, 3H), 1.85 (m, 2H);

13C NMR (100 MHz, CDCl3)

δ 137.94, 132.27, 129.19, 128.72, 128.17, 122.49, 92.16, 83.58, 68.31, 38.64, 21.20, 12.98; HRMS (EI+ , 70 eV): C13H14O [M]+ : calcd. 186.1045, found 186.1047

(E)-2-(fluoro(phenyl)methylene)cyclopentan-1-one (2a) Yield: 85%; Colorless oil;

1H NMR (400 MHz, CDCl3) δ 7.79 (dd, J = 8.0, 1.5 Hz, 2H), 7.46-7.40 (m, 3H), 2.94 (td, J = 7.3, 3.3 Hz, 2H), 2.43 (td, J = 7.9, 1.2 Hz, 2H),1.99 (m, 2H);

13C NMR (100 MHz, CDCl3) δ 204.7 (d, J = 14.4 Hz), 162.4 (d, J = 270.7 Hz), 131.1, 130.0, 129.7, 128.7 (d, J = 7.0 Hz), 127.8, 117.3 (d, J = 19.4 Hz), 40.7 (d, J = 4.3 Hz), 27.6 (d, J = 3.9 Hz), 19.4;

19F (376 MHz, CDCl3) δ -76.9;

HRMS (EI+ , 70 eV): C12H11FO [M]+ : calcd. 190.0794, found 190.0795.

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