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Sunday 6 November 2016

(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 Chena 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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Зопиклон , Zopiclone, زوبيكلون , 佐匹克隆


Zopiclone structure.svg
ZOPICLONE
зопиклон 
زوبيكلون 
佐匹克隆 
(±)-Zopiclone
1-Piperazinecarboxylic acid, 4-methyl-, 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin-5-yl ester 
256-138-9 [EINECS]
43200-80-2 [RN]


Structural formula

UV- Spectrum

Conditions : Concentration - 1 mg / 100 ml
The solvent designation schedule
methanol 
water 
0.1М HCl
0.1M NaOH
maximum absorptionThere 
decay
303 nm304 nm277 nm 
237 nm
-362364199
390
e-10500105005800
11300

IR - spectrum

Wavelength (μm)
Wave number (cm -1 )

MASS spectrum

Range
10 largest peaks:
Peak425699112139143217245246247
Value155231280283209999279719156250

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.


Brief background information

SaltATCformulaMMCASE
-N05CF0117 H 17 ClN 6 O 3388.82 g / mol43200-80-2

Application

  • sedative
  • hypnotic

Classes substance

  • chlorine compounds
    • oxo
      • Esters of 1-piperazinecarboxylate
        • pyridines
          • Pirrolo [3,4-b] piraziny

Synthesis Way

Синтез a)

Trade names

countryTradenameManufacturer
GermanyOptydormDOLORGIET
SomnosanHormos
KsimovanSanofi-Aventis
ZopHEXAL
Zopi-cigarActavis
various generic drugs
FranceimovaneSanofiAventis
NoktireksSanofi-Synthélabo
United KingdomSnowmanSanofiAventis
ItalyimovaneSanofiAventis
tionTHERE
JapanAmoʙanSanofi-Aventis; Chugai; Mitsubishi
UkraineimovaneSanofi Winthrop Indastria, France
various generic drugs

Formulations

  • coated tablets 7.5 mg;
  • Tablets 7.5 mg, 10 mg

References

  • DOS 2 300 491 (Rhône-Poulenc; appl. 5.1.1973; F-prior. 7.1.1972, 9.9.1972).
  • US 3 862 149 (Rhône-Poulenc; 21.1.1975; F-prior. 7.1.1972, 9.9.1972).


Two major zopiclone metabolites.
Two major zopiclone metabolites.





CAS Registry No.:43200-80-2
Molecular Formula:C17H17ClN6O3Molecular Weight:388.8
ChemicalStructure
Compound Name:
zopiclone
1-piperazinecarboxylic acid, 4-methyl-, 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo(3,4-b)pyrazin-5-yl ester
4-methyl-1-piperazinecarboxylic acid 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo(3,4-b)-pyrazin-5-yl ester
4-methyl-1-piperazinecarboxylic acid-6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo(3,4-b)-pyrazin-5-yl ester
6-(5-chloro-2-pyridyl)-6,7-dihydro-7-oxo-5H-pyrrolo(3,4-b)pyrazin-5-yl 4-methyl-1-piperazinecarboxylate
6-(5-chloro-pyridin-2-yl)-5((4-methyl-1-piperazinyl)carbonyloxy)-7-oxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine
6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazin-5-yl 4-methylpiperazine-1-carboxylate
amoban (R)
imovane



















Zopiclone (Imovance), 4-methyl-1-piperzinecarboxylic acid 6-(5-chloro-2- pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin-5-yl ester (Figure 1) is one of the non benzodiazepine sedative-hypnotics of the cyclopyrrolone class, sold by Rhone-Poulene Company in France since 1987. Although structurally unrelated to benzodiazepines, its pharmacological profile is similar, exhibiting sedative-hypnotic, anxiolytic, myorelaxant, and anticonvulsant activity.[1] Other than the first generation barbiturates and the second-generation benzodiazepines, zopiclone, which is widely used in Europe as well as other regions worldwide,[2,3] as a representative of the third generation sedative-hypnotic drugs, has been shown to be free from residual effects on performance and psychological function the day after intake and from the risks of accumulation because of its short elimination half-life (3.5 to 6.5 hours).[3,4] It is indicated for the short term treatment of insomnia, transient, situational or chronic insomnia, and insomnia secondary to psychiatric disturbances.[3]










REFERENCES 1. Mann, K.; Bauer, H.; Hiemke, C.; Ro¨schke, J.; Wetzel, H.; Benkert, O. Acute, subchronic and discontinuation effects of zopiclone on sleep EEG and nocturnal melatonin secretion. Eur. Neuropsychopharm. 1996, 6 (3), 163– 168. Structure Elucidation of Sedative-Hypnotic Zopiclone 359 Downloaded by [Dalhousie University] at 22:10 19 December 2012

 2. Le´ger, D.; Janus, C.; Pellois, A.; Quera-Salva, M.A.; Dreyfus, J.P. Sleep, morning alertness and quality of life in subjects treated with zopiclone and in good sleepers. study comparing 167 patients and 381 good sleepers. Eur. Psychiat. 1995, 10 (973) Suppl. 3, 99s – 102s.

3. Piperaki, S.; Parissi-Poulou, M. Enantiomeric separation of zopiclone, its metabolites and products of degradation on a b-cyclodextrin bonded phase. J. Chromatogr. A 1996, 729 (1 – 2), 19 – 28



Spectral Data Analyses and Structure Elucidation of Sedative‐Hypnotic Zopiclone

Pages 349-360 | Received 10 Sep 2006, Accepted 18 Oct 2006, Published online: 13 Oct 2010


Zopiclone
Zopiclone structure.svg
Zopiclone ball-and-stick.png
Systematic (IUPAC) name
(RS)-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate
Clinical data
Trade namesImovane, Zimovane
AHFS/Drugs.comInternational Drug Names
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
    Routes of
    administration
    Oral tablets, 3.75 mg (UK), 5 or 7.5 mg
    Legal status
    Legal status
    • AU: S4 (Prescription only)
    • UK: Class C (POM)
    • US: Schedule IV
    Pharmacokinetic data
    Bioavailability75-80%[1]
    Protein binding52–59%
    MetabolismHepatic through CYP3A4and CYP2E1
    Biological half-life~5 hours (3.5–6.5 hours)
    ~7–9 hours for over 65
    ExcretionUrine (80%)
    Identifiers
    CAS Number43200-80-2 Yes
    ATC codeN05CF01 (WHO)
    PubChemCID 5735
    IUPHAR/BPS7430
    DrugBankDB01198 Yes
    ChemSpider5533 Yes
    UNII03A5ORL08Q Yes
    KEGGD01372 Yes
    ChEBICHEBI:32315 Yes
    ChEMBLCHEMBL135400 Yes
    PDB ligand IDZPC (PDBeRCSB PDB)
    Chemical data
    FormulaC17H17ClN6O3
    Molar mass388.808 g/mol
    3D model (Jmol)Interactive image




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