2 BUTANONE .....SPECTROSCOPY PROBLEM

Butanone, also known as methyl ethyl ketone or MEK, is an organic compound with the formula CH₃C(O)CH₂CH₃. This colorless liquid ketone has a sharp, sweet odor reminiscent of butterscotch and acetone. It is produced industrially on a large scale, and also occurs in trace amounts in nature. It is soluble in water and is commonly used as an industrial solvent

Example 

C₄H₈O
MW 72
First calculate the degree of unsaturation: the answer is 1. This means that the compound has four carbons and an oxygen, it can have a carbon-carbon double bond, a carbon-oxygen double bond - a carbonyl, or a ring.

IR Spectrum

A table of characteristic IR absorptions is available online: click on the link below. Note that this chart is also linked to in the frame to the left.
The IR spectrum for Example 1 is below. Since the degree of unsaturation indicates that the compound could have a carbonyl, let's look for that first, since carbonyl bands are strong and distinct. Carbonyls show up in the region 1760-1665, and specifically, saturated aliphatic ketone close to 1715. Sure enough, there is a band at 1718 indicating a saturated aliphatic ketone.

Think of possible structures

Now we know that the compound has a carbon-oxygen double bond, but there are still a few ways that this four-carbon molecule could be put together. Examples are below:

The second and third structures above are saturated aliphatic aldehydes, which show up at 1740-1720. While in the above IR spectrum the band at 1715 might be close to the range of saturated aliphatic aldehydes, an aldehyde would also show a distinct band for H-C=O stretch in the region 2830-2695, so it is not likely that it is one of these structures. That leaves the first compound, which is 2-butanone.

Proton NMR Spectrum

A table of characteristic NMR shifts is available online: click on the link below. Note that this chart is also linked to in the frame to the left.

• Before you look at the NMR spectrum, think about what the spectrum of 2-butanone should look like. There are three different types of protons:

The 3 protons in green will be a singlet and show up from 2-2.7 ppm. The 2 protons in blue will be split to a quartet by the protons in red; they will show up from 2-2.7 ppm. They will be further downfield (have a higher ppm value) than the protons in green because they are shielded both by the carbonyl and by the red methyl group. The 3 red protons are the farthest from the carbonyl and are split into a triplet by the blue protons. Let's look at the NMR and see if this is what we see.

Sure enough, here is how they correlate with the structure:

Note the pattern of the ethyl group -CH₂CH₃ in the above NMR spectrum. Whenever you suspect an ethyl group in a molecule, look for a quartet of 3 protons and a triplet of 2 protons, with the methylene (-CH₂-) group further downfield than the methyl group (-CH₃).

Summary

Example 1 is 2-butanone:

COSY

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/