DR ANTHONY MELVIN CRASTO,WorldDrugTracker, helping millions, A 90 % paralysed man in action for you, I am suffering from transverse mylitis and bound to a wheel chair, With death on the horizon, nothing will not stop me except God................DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai) , INDIA 25Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK GENERICS at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational contribution

Saturday 5 April 2014

J-HMBC / Broadband XLOC

J-HMBC / Broadband XLOC

Measurement of long-range J(X,H) and J(H,H) coupling constants.

Sequences


J-HMBC and constant-time J-HMBC for measurement of long-range J(X,H) coupling constants
  • tau 1 = ( 2×(Jmin + 0.070(Jmax - Jmin)))-1
  • tau 2 = ( Jmax + Jmin)-1
  • tau 3 = ( 2×(Jmax - 0.070(Jmax - Jmin)))-1
  • sum tau i: duration of low-pass J filter (LPJF)
  • kappa : scaling factor for apparent upscaling of nJ(X,H)
  • Delta = kappa × t1max
  • tA = 0.5 × ( Delta - sum tau i + t1max) - delta
  • tB = 0.5 × ( Delta + t1max - (1 + kappa )×t1)
  • tC = 0.5 × ( kappa ×t1 + sum tau i) + delta
  • delta = gradient delay
  • Gradient ratios:
    • LPJF: +7, -4, -2, -1
    • Echo: +5.0 : -3.0
    • Antiecho: -3.0 : +5.0

Broadband XLOC for measurement of J(H,H) coupling constants
  • tau 1 = ( 2×(Jmin + 0.070(Jmax - Jmin)))-1
  • tau 2 = ( Jmax + Jmin)-1
  • tau 3 = ( 2×(Jmax - 0.070(Jmax - Jmin)))-1
  • sum tau i: duration of low-pass J filter (LPJF)
  • Delta : Excitation delay
  • delta = gradient delay
  • Gradient ratios:
    • LPJF: +7, -4, -2, -1
    • Echo: +5.0 : -3.0
    • Antiecho: -3.0 : +5.0

Results

Expansion of a constant-time J-HMBC spectrum of 15 µl of ethyl trans-cinnamate in 600 µl CDCl3 at 25° C. Delta = 500 ms, kappa = 22;
F1 sections from J-HMBC spectra of 15 µl of ethyl trans-cinnamate in 600 µl CDCl3 at 25° C. Delta = 500 ms and kappa = 22 which results in an apparent splitting of the doublet components by kappa J relative to the 13C chemical shifts.
Expansion from a Broadband XLOC spectrum of 15 µl of ethyl trans-cinnamate in 600 µl CDCl3 at 25° C. with F2traces suitable for measurement of J(H,H) coupling constants.

References

  • Meissner, A. and Sorensen, O.W. Measurement of J(H,H) and long-range J(X,H) coupling constants in small molecules. Broadband XLOC and J-HMBC Magn.Reson.Chem. 39 49-522001

ETHYL ACETATE THE BASIC NMR LEARNING TOOL


ETHYL ACETATE



1H NMR



The ethyl acetate spectrum displays the typical quartet and triplet of a substituted ethyl group.











13CNMR
proton-decoupled13C-NMR spectrum of ethyl acetate, showing the expected four signals, one for each of the carbons.

image104.png

Wednesday 2 April 2014

Ranbezolid from Ranbaxy as an oxazolidinone antibacterial

Ranbezolid structure.svg

Ranbezolid

392659-39-1 hydrochloride
392659-38-0 (free base)
N-{[(5S)-3-(3-Fluoro-4-{4-[(5-nitro-2-furyl)methyl]-1-piperazinyl}phenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide
(S)-N-[[3-fluoro-4-[N-1[4-{2-furyl-(5-nitro)methyl}]piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]-methyl]acetamide

  • Mp: 207–209 °C.
  •  1H NMR (DMSO, 300 MHz):  
    δ 8.30 (t, 1H, –NHCO–), 
    7.75 (d, J = 3.3 Hz, 1H, furyl–H), 
    7.52 (dd, 1H, phenyl–H), 
    7.3–7.0 (m, 3H, phenyl–H, furyl–H), 
    4.70 (m, 1H, oxazolidinone ring C5H), 
    4.63 (s, 2H), 
    4.08 (t, J = 8.8 Hz, 1H, –CH2–), 
    3.73 (t, J = 7.5 Hz, 1H), 
    3.43 (br m, piperazine–H merged with H2O in DMSO), 
    .83 (s, 3H, –COCH3).
  • HPLC purity: 98%. 
    Anal. Calcd for C21H25ClN5O6·0.5H2O: C, 50.76; H, 5.48; N, 14.09. Anal. Found: C, 50.83; H, 5.17; N, 13.83.

MK 2048 an HIV integrase inhibitor from Merck


Structure of MK-2048 with important pharmacophore highlighted

…………………..


File:MK-2048.svg
MK 2048
Molecular Formula: C21H21ClFN5O4   Molecular Weight: 461.873943


MK 2048
lH NMR (400 MHz, CDCI3) δ 7.48 (dhttp://newdrugapprovals.org/2014/04/02/mk-2048-an-hiv-integrase-inhibitor/d, 7 = 7.0, 2.2 Hz, IH), 7.33 (m, IH), 7.09 (t, 7 = 8.7 Hz, IH), 6.01 (m, IH), 5.33 (d, 7= 14.1 Hz, IH), 5.27 (d, 7 = 14.1 Hz, IH), 3.99 (dd, 7= 12.8, 4.0 Hz, 1 H), 3.71(heptet, 7 = 7.1 Hz, 1 H), 3.49 (heptet, 7 = 7.1 Hz, 1 H), 3.24 (dd, 7 = 13.2, 1.5 Hz, 1 H), 3.03 (d, 7 = 5.1 Hz, 3H), 1.42 (d, 7 = 6.6 Hz, 3H), 1.24 (t, 7 = 7.3 Hz, 3H). 

Saturday 15 March 2014

Vanillin, Organic spectroscopy

Vanillin, a promising biobased building-block for monomer synthesis










Green Chem., 2014, Advance Article
DOI: 10.1039/C3GC42613K, Paper
Maxence Fache, Emilie Darroman, Vincent Besse, Remi Auvergne, Sylvain Caillol, Bernard Boutevin
Corresponding authors
a
Institut Charles Gerhardt, UMR CNRS 5253, Equipe Ingénierie et Architectures Macromoléculaires, ENSCM, 8 rue de l'Ecole Normale, 34296 Montpellier, France
b
COLAS S.A., 7 place René Clair, 92653 Boulogne-Billancourt, France

We report the synthesis of new aromatic biobased building-blocks from vanillin, for their promising use in polymer synthesis.



Vanillin was used as a renewable building-block to develop a platform of 22 biobased compounds for polymer chemistry. Vanillin-derived biobased monomers bearing epoxy, cyclic carbonates, allyl, amine, alcohol and carboxylic acid moieties were synthesized. They can be used, among many others, in epoxy, polyester, polyurethanes, and Non-Isocyanate PolyUrethanes (NIPU) polymer synthesis. The epoxy-functionalized compounds were synthesized under solvent-free conditions and are original biobased aromatic epoxy monomers. Cyclic carbonates were prepared through a catalytic reaction between epoxy compounds and CO2. Thiol–ene reactions allowed the functionalization of allylated compounds with amines, acids and alcohols. The amine-functionalized compounds are, to our knowledge, the first non-aliphatic biobased amine hardeners, usable either in epoxy or NIPU materials.

1H (proton) NMR spectrum for 0.037 grams of vanillin in .5 milliliters of CDCl3 (deuterated trichloromethane) taken at 89.56 MHz showing location correlated peaks.


Skeletal formula of a vanillin minor tautomerVANILLIN





13C NMR

This 13C spectrum exhibits resonances at the following chemical shifts:
Shift (ppm)
191.6128.0
152.4115.0
147.7109.4
130.056.6
Point to a peak to learn more about it. Note: The peak at 130.4 ppm is much smaller than the one at 130.5 ppm. Also, the 1H spectrum is often helpful.

13C NMR





This 13C spectrum exhibits resonances at the following chemical shifts:
Shift (ppm)
191.6C=O
152.4CH OF OCH3
147.7CH OF OH
130.0 CH OF CHO
Point to a peak to learn more about it. Note: The peak at 130.4 ppm is much smaller than the one at 130.5 ppm. Also, the 1H spectrum is often helpful.
128   CH ON AROM RING PARA TO OH, ORTHO TO CHO
115.0    CH ON AROM RING ORTHO TO OH AND CHO FUNCTIONS
109.4      CH ON AROM RING ORTHO TO OCH3 AND META TO OH
56.0           OCH3



1D DEPT90
spectrum for vanillin



2D [1H,13C]-HMBC
spectrum for vanillin



2D [1H,13C]-HSQC
spectrum for vanillin


2D [1H,1H]-COSY

spectrum for vanillin

Chemical synthesis

The demand for vanilla flavoring has long exceeded the supply of vanilla beans. As of 2001, the annual demand for vanillin was 12,000 tons, but only 1,800 tons of natural vanillin were produced. The remainder was produced by chemical synthesis. Vanillin was first synthesized from eugenol (found in oil of clove) in 1874–75, less than 20 years after it was first identified and isolated. Vanillin was commercially produced from eugenol until the 1920s. Later it was synthesized from lignin-containing "brown liquor", a byproduct of the sulfite process for making wood pulp.[9] Counter-intuitively, even though it uses waste materials, the lignin process is no longer popular because of environmental concerns, and today most vanillin is produced from the petrochemical raw material guaiacol. Several routes exist for synthesizing vanillin from guaiacol.
At present, the most significant of these is the two-step process practiced by Rhodia since the 1970s, in which guaiacol (1) reacts with glyoxylic acidby electrophilic aromatic substitution. The resulting vanillylmandelic acid (2) is then converted via 4-Hydroxy-3-methoxyphenylglyoxylic acid (3) to vanillin (4) by oxidative decarboxylation.[4]
Synthesis vanillin 4.svg

Friday 21 February 2014

NICOTINE .......FRIEND FOR ORGANIC SPECTROSCOPY



File:Nicotine3Dan2.gif



NICOTINE
(-)-NICOTINE is classified as super toxic. Probable oral lethal dose in humans is less than 5 mg/kg or a taste (less than 7 drops) for a 70 kg (150 lbs.) person. It may be assumed that ingestion of 40-60 mg of nicotine is lethal to humans. There is fundamental difference between acute toxicity from use of nicotine as insecticide or from ingestion, and chronic toxicity that may be caused by prolonged exposure to small doses as occurs in smoking. Maternal smoking during pregnancy is associated with increased risk of spontaneous abortion, low birth weight and still-birth. Nicotine was found as a co-carcinogen in animals.

An alkaloid produced from tobacco. Colorless, oily liquid, combustible, highly toxic. When heated to decomposition (-)-NICOTINE(54-11-5) emits very toxic fumes of carbon monoxide and oxides of nitrogen [Lewis, 3rd ed., 1993, p. 919].


Properties of Nicotine  


FormulaC10H14N2
Molecular Weight162,234 g.mol-1
Melting point-7,9 ° C
Boiling point247 ° C
Rotatory index (S)
aD = -168    at 20° C
Densityd=1,010
Refractive indexn=1,530
Comments    Pale yellow to dark brown liquid with a slight, fishy odor when warm.
    Insecticide.


1D 1H(+/-) Nicotine

spectrum for (+/-) Nicotine



2D [1H,1H]-TOCSY(+/-) Nicotine
spectrum for (+/-) Nicotine


1D 13C(+/-) Nicotine
spectrum for (+/-) Nicotine


1D DEPT90(+/-) Nicotine

spectrum for (+/-) Nicotine


1D DEPT135(+/-) Nicotine


spectrum for (+/-) Nicotine



2D [1H,13C]-HSQC(+/-) Nicotine


spectrum for (+/-) Nicotine

IR analysis



On this spectrum, we can notice several peaks, which characterise the different chemical functions of nicotine: 
·    Around 3400 cm-1, we can see the large peak of water (it deals with a liquid film).
·    Between 2970 and 2780 cm-1 : C-H stretching.
·    The peak at 1677 cm-1 : aromatic C=N double bond stretching.
·    The peak at 1691 cm-1 : aromatic C=C double bond stretching.
·    The peaks at 717 cm-1 and 904 cm-1 correspond to the out of plane bending of the C-H bond of the monosubstituted pyridinic cycle.

Mass spectrum analysis

We can notice the molecular peak at 162 m/z. However, the biggest peak is at 84 m/z. It corresponds to the fragmentation of nicotine. It deals with the pyrrolidine cycle, which has this molecular weight. During the electronic bombardment, the nicotine was split between the two cycles. 

1H-RMN analysis in CDCl3 (400MHz)



 Assignment   
Chemical shift (ppm)

A

8,543

B

8,487

C

7,711

D

7,255

E

3,237

F

3,087

G

2,307

J

2,200

K

2,160

L

1,958

M

1,820

N

1,725

Done with C-H   COSY      


13C-RMN analysis in CDCl3


AssignmentChemical shift (ppm)Integration
1149,45750
2
148,51
783
3138,80517
4134,86917
5123,54894
668,831000
756,96844
840,32783
935,23833
1022,60839

L-Nicotine
CAS:54-11-5





Nicotine biosynthesis