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

•  1 = ( 2×(Jmin + 0.070(Jmax - Jmin)))-1
•  2 = ( Jmax + Jmin)-1
•  3 = ( 2×(Jmax - 0.070(Jmax - Jmin)))-1
•   i: duration of low-pass J filter (LPJF)
•  : scaling factor for apparent upscaling of nJ(X,H)
•  =  × t1max
• tA = 0.5 × (  -   i + t1max) - 
• tB = 0.5 × (  + t1max - (1 +  )×t1)
• tC = 0.5 × (  ×t1 +   i) + 
•  = 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

•  1 = ( 2×(Jmin + 0.070(Jmax - Jmin)))-1
•  2 = ( Jmax + Jmin)-1
•  3 = ( 2×(Jmax - 0.070(Jmax - Jmin)))-1
•   i: duration of low-pass J filter (LPJF)
•  : Excitation delay
•  = 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.  = 500 ms,  = 22;
F1 sections from J-HMBC spectra of 15 µl of ethyl trans-cinnamate in 600 µl CDCl3 at 25° C.  = 500 ms and  = 22 which results in an apparent splitting of the doublet components by  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.

Ranbezolid from Ranbaxy as an oxazolidinone antibacterial

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

 http://newdrugapprovals.org/2014/04/02/ranbezolid-from-ranbaxy-as-an-oxazolidinone-antibacterial/

• 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 C₅–H), 
  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

…………………..

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). 

ES MS M+l = 462

 http://newdrugapprovals.org/2014/04/02/mk-2048-an-hiv-integrase-inhibitor/

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.

http://pubs.rsc.org/en/Content/ArticleLanding/2014/GC/C3GC42613K?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

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.


VANILLIN





13C NMR

This ¹³C spectrum exhibits resonances at the following chemical shifts:

Shift (ppm)
191.6	128.0
152.4	115.0
147.7	109.4
130.0	56.6

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)
191.6	C=O
152.4	CH OF OCH3
147.7	CH 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




2D [1H,13C]-HMBC




2D [1H,13C]-HSQC



2D [1H,1H]-COSY

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]

Zotarolimus, ABT 578 « New Drug Approvals

Zotarolimus, ABT 578 « New Drug Approvals:



'via Blog this'

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

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  

Formula	C10H14N2
Molecular Weight	162,234 g.mol-1
Melting point	-7,9 ° C
Boiling point	247 ° C
Rotatory index (S)	aD = -168    at 20° C
Density	d=1,010
Refractive index	n=1,530
Comments	Pale yellow to dark brown liquid with a slight, fishy odor when warm.     Insecticide.

1D 1H(+/-) Nicotine





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



1D 13C(+/-) Nicotine



1D DEPT90(+/-) Nicotine




1D DEPT135(+/-) Nicotine






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

Assignment	Chemical shift (ppm)	Integration
1	149,45	750
2	148,51	783
3	138,80	517
4	134,86	917
5	123,54	894
6	68,83	1000
7	56,96	844
8	40,32	783
9	35,23	833
10	22,60	839

L-Nicotine

CAS:54-11-5

Nicotine biosynthesis