COSY NMR Spectroscopy

...........
https://www.youtube.com/watch?v=37g2t2XJhxU

¹H-¹H COSY (COrrelation SpectroscopY) 

¹H-¹H COSY is used for clearly indicate correlation with coupled protons. A point of entry into a COSY spectrum is one of the keys to predict information from it successfully. Relation of Coupling protons is determined by cross peaks(correlation peaks) and in the COSY spectrum. In other words, Diagonal peaks by lines are coupled to each other. Figure 12 indicates that there are correlation peaks between proton H₁ and H₂ as well as between H₂ and H₄. This means the H₂ coupled to H₁and H₄. 

Fig 12. ¹H-¹H COSY spectrum

¹H-¹³C COSY (HETCOR) 

¹H-¹³C COSY is the heteronuclear correlation spectroscopy. The HETCOR spectrum is correlated ¹³C nuclei with directly attached protons. ¹H-¹³C coupling is one bond. The cross peaks mean correlation between a proton and a carbon (Fig 13). If a line does not have cross peak, this means that this carbon atoms has no attached proton (e.g. a quaternary carbon atom) 

Fig 13.  ¹H-¹³C COSY  spectrum

How To Read COSY Spectra

2-Nitropropane:  To see what type of information a COSY spectrum may provide. we shall consider several examples of increasing complexity. The first is the COSY spectrum of 2-nitropropane. In this simple molecule, we expect to observe coupling between the protons on the two methyl groups and the proton at the methine position.

Figure 1 is the COSY spectrum of 2-nitropropane. The first thing to note about the spectrum is that the proton NMR spectrum of the compound being studied is plotted along both the horizontal and vertical axes, and each axis is calibrated according to the chemical shift values (in parts per million , ppm). The COSY spectrum shows distinct spots on a diagonal. extending from the upper right corner of the spectrum down to the lower left corner. By extending vertical and horizontal lines from each spot on the diagonal, you call easily see that each spot on the diagonal corresponds with the same peak on each coordinate axis

Figure 1,  COSY spectrum of 2-nitropropane.

The diagonal peaks serve only as reference points. The important peaks in the spectrum are the oil-diagonal peaks. In the spectrum of 2-nitropropane, we can extend a horizontal line from the spot at 1.56 ppm (which is labeled A and corresponds to the methyl protons).  This horizontal line eventually encounters an off-diagonal spot (al the upper left of the COSY spectrum) that corresponds to the methine proton peak at 4.66 ppm (labeled B). A vertical line drawn from this off diagonal spot intersects the spot on the diagonal that corresponds to the methine proton (B). The presence of this off-diagonal spot, which correlates the methyl proton spot and the methine proton spot, confirms that the methyl protons arc coupled to the methine protons. as we would have expected. A similar result would have been obtained by drawing a vertical line from the 1.56-ppm spot (A) and at horizontal line from the 4.66-ppm spot (B). The two lines would have intersected at the second off-diagonal spot (at the lower right of the COSY spectrum). The vertical and horizontal lines described in this analysis are drawn on the COSY spectrum in Figure 1.

Isopentyl Acetate. In practice, we would not require a COSY spectrum to fully interpret the NMR spectrum of 2-nitropropane. The preceding analysis illustrated how to interpret a COSY spectrum, using a simple. easy-to-understand example. A more interesting example is the COSY spectrum of isopentyl acetic (Fig. 2).

Again we see coordinate axes; the proton spectrum of isopentyl acetate is plotted along each axis. The COSY spectrum shows a distinct set of spots on a diagonal, with each spot corresponding to the same peak on each coordinate axis. Lines have been drawn to help you identify the correlations. In the COSY spectrum of isopentyl acetate, we see that the protons of the two equivalent methyl groups (1) correlate with the methine proton (2). We can also see correlation between the two methylene groups (3 and 4) and between the methine proton (2) and the neighboring methylene (3). The methyl group of the acetatemoiety (6) docs not show off-diagonal peaks. because theacetyl methyl protonsare not coupled to other protons in the molecule.

Figure 2, COSY spectrum of isopentyl acetate.

You may have noticed that each of the COSY spectra shown in this section contains additional spots besides the ones examined in our discussion. Often these "extra" spots have much lower intensities than the principal spots on the plot. The COSY method can sometimes detect interactions between nuclei over ranges that extend beyond three bonds. Besides this long-range coupling, nuclei that are several atoms apart but that are close together spatially also may produce off-diagonal peaks. We learn to ignore these minor peaks in our interpretation of COSY spectra.  In some variations of the method, however, spectroscopist make use of such long-range interactions to produce two-dimensional NMR spectra that specifically record this type of information.

Citronellol.  The COSY spectrum of citronellol is a third example. The spectrum (Figure 3) is rather complex in appearance. Nevertheless, we can identify certain important coupling interactions. Again, lines have been drawn to help you identify the correlations. The proton on C6 is clearly coupled to the protons on C5.  Closer examination of the spectrum also reveals that the proton on C6 is coupled through allylic (four-bond) coupling to the two methyl groups at C8 and C9. The protons on C1 are coupled to two nonequivalent protons on C2 (at 1.4 and 1.6 ppm). They are nonequivalent, owing to the presence of a stereocenter in the molecule at C3. The splitting of the methyl protons at C10 by the methine proton at C3 can also be seen. although the C3 spot on the diagonal line is obscured by other spots that are superimposed on it. However, from the COSY spectrum we can determine that the methine proton at C3 must occur at the same chemical shift as one of the C8 or C9 methyl groups (1.6 ppm). Thus, a great deal of useful information can be obtained even from a complicated COSY pattern.

Figure 3  COSY spectrum of citronellol

How To Read HETCOR Spectra

2-Nitropropane. Figure 4 is an example of a simple HETCOR plot. In this case, the sample is 2-nitropropane.

It is common practice to plot the proton spectrum of the compound being studied along one axis and the carbon spectrum along the other axis. Each spot of intensity on the two-dimensional plot indicates a carbon atom that bears the corresponding protons. In Figure 4. you should be able to see a peak corresponding to the methyl carbons. which appear at 21 ppm in the carbon spectrum (horizontal axis), and a peak at 79 ppm corresponding to the methine carbon. On the vertical axis, you should also be able to find the doublet for the methyl protons at 1.56 ppm (proton spectrum) and a septet for the methine proton at 4.66 ppm.

FIGURE 4 HERTCOR spectrum of 2-nitropropane.

If you draw a vertical line from the methyl peak of the carbon spectrum (21 ppm) and a horizontal line from the methyl peak of the proton spectrum (1.56 ppm), the two lines would intersect at the exact point on the two-dimensional plot where a spot is marked. This spot indicates that the protons at 1.56 ppm and the carbons at 21 ppm represent the same position of the molecule. That is, the hydrogens are attached to the indicated carbon. In the same way, the spot in the lower left corner of the HETCOR plot correlates with the carbon peak at 79 ppm and the proton septet at 4.66 ppm, indicating that these two absorptions represent the same position in the molecule.

Isopentyl Acetate. A second, more complex example is isopentyl acetate. Figure 5 is the HETCOR plot for this substance.  Each spot on the HETCOR plot has been labeled with a number and lines have been drawn to help you see the correlations between proton peaks and carbon peaks. The carbon peak at 23 ppm and the proton doublet at 0.92 ppm correspond to the methyl groups (1); the carbon peak at 25 ppm and the proton multiplet at 1.69 ppm correspond to the methine position (2); and the carbon peak at 37 ppm and the proton quartet at 1.52ppm correspond to the methylene group (3). The other methylene group (4) is deshielded by the nearby oxygen atom. Therefore, a spot on the HETCOR plot for this group appears at 63 ppm on the carbon axis and 4.10 ppm on the proton axis. It is interesting that the methyl group of the acetyl function (6) appears down field of the methyl groups of the isopentyl group (1) in the proton spectrum (2.04 ppm). We expect this chemical shift, since the methyl protons should be deshielded by the anisotropic nature of the carbonyl group. In the carbon spectrum, however. the carbon peak appears upfield of the methyl carbons of the isopentyl group.  A spot on theHETCOR plot that correlates these two peaks confirms the assignment.

Figure 5. HETCOR spectrum of isopentyl acetate.

4-Methyl-2-Pentanol.  Figure 6 shows the final example that illustrates some of the power of the HETCOR technique for 4-methyl-2-pentanol. Lines have been drawn on the spectrum to help you find the correlations. This molecule has a stereocenter atcarbon 2.  An examination of the HETCOR plot for 4-methyl-2-pentanol reveals two spots that correspond to the two methylene protons on carbon 3.  At 48 ppm on the carbon axis. two contour spots appear, one at about 1.20 ppm on the proton axis and the other at about 1.40 ppm. The HETCOR plot shows that there are two nonequivalent protons attached to carbon 3.  If we examine a Newman projection of this molecule, we find that the presence of the stereocenter makes the two methylene protons (a and b) nonequivalent. As a result, they appear at different values of chemical shift.

                 

The carbon spectrum also reveals the effect of a stereocenter in the molecule. In the protonspectrum, the apparent doublet (actually it is apair of doublets) at 0.91 ppm arises from the sixprotons on the methyl groups, which are labeled 5 and 6 in the preceding structure. Looking across to the right on the HETCOR plot, you will find twocontour spots, one corresponding to 22 ppm and the other corresponding to 23 ppm. These two carbon peaks arise because the two methyl groups are also not quite equivalent; the distance from one methyl group to the oxygen atom is not quitethe same as that from the other methyl group, when we consider the most likely conformation for the molecule.

FIGURE 6  HETCOR spectrum of 4-methyl-2-pentanol.

A great many advanced techniques can be applied to complex molecules.  We have introduced only a few of the most important ones here. As computers become faster and more powerful, as chemists evolve their understanding of what different pulse sequences can achieve. and as scientists write more sophisticated computer programs to control those pulse sequences and treat data, it will become possible to apply NMR spectroscopy to increasingly complex systems.

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Join me on Linkedin

Join me on Facebook FACEBOOK

Join me on twitter     

Join me on google plus Googleplus

 amcrasto@gmail.com

KHAJURAHO INDIA

Location of Khajuraho Group of Monuments in India.

Location in Madhya Pradesh

1. Khajuraho Group of Monuments - Wikipedia, the free ...

   en.wikipedia.org/wiki/Khajuraho_Group_of_Monuments
   

   
   

   • 
     
   • 
     

   The Khajuraho Group of Monuments are a group of Hindu and Jain temples in Madhya Pradesh, India. About 620 kilometres (385 mi) southeast of New Delhi, ...

Hotel Chandela - A Taj Leisure Hotel

Silodosin

SILODOSIN

Urief, 160970-54-7, Rapaflo, KMD 3213, Silodyx, KAD 3213, KMD-3213

Molecular Formula: C₂₅H₃₂F₃N₃O₄

Molecular Weight: 495.53449 g/mol

Alpha 1A adrenoceptor antagonist

Prostate hyperplasia

Kissei Pharmaceutical Co Ltd  INOVATOR

CAS 160970-54-7

2,3-Dihydro-1-(3-hydroxypropyl)-5-[(2R)-2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-1H-indole-7-carboxamide

160970-64-9 (racemate)
169107-04-4 (diHBr)

Properties: [a]D25 -14.0° (c = 1.01 in methanol).

Optical Rotation: [a]D25 -14.0° (c = 1.01 in methanol)

Therap-Cat: In treatment of benign prostatic hypertophy.

a-Adrenergic Blocker.

synthesis..............http://newdrugapprovals.org/2015/02/20/silodosin-for-treatment-of-benign-prostatic-hypertophy/

CN101993407

http://www.google.com/patents/CN101993407B?cl=en

silodosin for selective inhibition of urethral smooth muscle contraction and reduce the pressure within the urethra, but no significant impact on blood pressure, for the treatment of benign prostatic hyperplasia. At present, the method of synthesis Silodosin many reports, but the lack of high yield method for industrial production.

  JP200199956 reported that benzoic acid as a starting material, 1_ (3_ benzoyloxy-propyl) indoline hydrochloride (structural formula (1), R is a hydrogen atom) in 60% yield, then through the multi-step reaction was further prepared silodosin intermediate 1- (3-benzoyloxy-propyl) -5- (2-nitro-propyl) -7-cyano-indoline (structural formula VIII ), the total yield is low, and only 20 percent. Compound (VIII) with potassium carbonate, the reaction of hydrogen peroxide to yield compound (IX), impurities, and purified by column chromatography to be not suitable for industrial production. Compound (IX) under catalysis of molybdenum oxide, and L- (S) – benzyl glycyl alcohol asymmetric reactions, protecting groups may be due to steric hindrance is small, low chiral induction, is 3.8: I.

Silodosin Preparation: 12  Example

  Example 11 to give 8 g solid, dissolved in DMSO 100ml, was added 5mol / L NaOH 12ml, 18 ~ 20 ° C was added dropwise slowly with 30% H2027 grams, then 30 ° C, the reaction ended 4h. Extracted with ethyl acetate, the combined organic layer was washed 2N HCl and then the organic layer, the aqueous layer was neutralized with sodium hydroxide, and then extracted with ethyl acetate, washed with saturated sodium bicarbonate, dried over anhydrous sodium sulfate, and evaporated concentrated and then dissolved in ethyl acetate, natural cooling crystallization, filtration, drying 5 g (87%), purity> 99%.

 

  Mp 105 ~ 108 ° C

  [a] 20d = -16.2 C = I, MeOH

  1NMR spectrum (DMS0-d6): δ ppm 0.9-1.0 (3H, d), 1.5-1.6 (1H, s), 1.6-1.7 (2H, m),

2.3-2.4 (1H, dd), 2.6-2.7 (1H, dd), 2.8-3.0 (5H, m), 3.1-3.2 (2H, m), 3.3-3.4 (2H, m),

3.4-3.5 (2H, t), 4.0-4.1 (2H, t), 4.2-4.3 (1H, s), 4.6-4.8 (2H, t), 6.9-7.15 (6H, m),

7.2-7.3 (1H, s), 7.5-7.6 (1H, s)

synthesis..............http://newdrugapprovals.org/2015/02/20/silodosin-for-treatment-of-benign-prostatic-hypertophy/
सुकून उतना ही देना प्रभू, जितने से
जिंदगी चल जाये।
औकात बस इतनी देना,
कि औरों का भला हो जाये।
synthesis..............http://newdrugapprovals.org/2015/02/20/silodosin-for-treatment-of-benign-prostatic-hypertophy/



सुकून उतना ही देना प्रभू, जितने से
जिंदगी चल जाये।
औकात बस इतनी देना,
कि औरों का भला हो जाये।

 COCK WILL TEACH YOU

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Join me on Linkedin

Join me on Facebook FACEBOOK

Join me on twitter     

Join me on google plus Googleplus

 amcrasto@gmail.com

3-Methyl-1-oxa-2,7-diaza-7,10-ethanospiro[4.5]dec-2-ene

10a R= methyl

3-Methyl-1-oxa-2,7-diaza-7,10-ethanospiro[4.5]dec-2-ene (10a)

Data

10a ...............(960 mg, 82%) as a colorless oil. 

1 H NMR (300 MHz) δ 1.38–2.10 (m, 4H), 1.97 (s, 3H), 2.40 (m, 1H), 2.68 (d, J = 17.2 Hz, 1H), 2.68–3.00 (m, 4H), 2.92 (d, J = 14.4 Hz, 1H), 3.05 (d, J = 17.2 Hz, 1H), 3.24 (d, J = 14.4 Hz, 1H).

13C NMR (75.4 MHz) δ 13.4, 21.2, 23.6, 30.8, 46.3, 46.6, 48.4, 63.1, 85.3, 154.4. 


IR (thin film) υmax 2948, 2874, 1630, 1457, 1434, 1388, 1332, 1219, 1072, 1050, 1038, 982, 897, 800, 688, 630 cm–1. 

LRMS (EI) m/z (%) 180 (M+•, 0.8), 167 (6), 149 (21), 139 (63), 124 (7), 111 (3), 96 (100), 82 (43), 69 (49), 55 (44). 

HRMS (EI) Found m/z 180.1264 (M+•). C10H16N2O requires m/z 180.1263. 



Synthesis of spiroisoxazolines through cycloadditions of nitrile oxides with 3-methylenequinuclidine (JC-1605EP) 
Connie K. Y. Lee, Christopher J. Easton, G. Paul Savage and Gregory W. Simpson
Full Text: PDF (289K)
pp. 175 - 183 

received Jul 15 2005; accepted Sep 8 2005; published Sep 10 2005;
Synthesis of spiroisoxazolines through cycloadditions of nitrile oxides with 3-methylenequinuclidine 
Connie K. Y. Lee,a Christopher J. Easton,*a G. Paul Savage,b and Gregory W. Simpsonb 

a Research School of Chemistry, Australian National University, Canberra ACT 0200, Australia, 
and b CSIRO Molecular and Health Technologies, Bayview Ave, Clayton VIC 3168, Australia 
E-mail: easton@rsc.anu.edu.au 
http://www.arkat-usa.org/arkivoc-journal/browse-arkivoc/2006/3/graphical-abstracts/
http://www.arkat-usa.org/get-file/20010/

This paper is dedicated to Professor James M. Coxon (Jim) on the occasion of his 65th birthday, and in recognition of his many contributions to chemistry  




Professor Christopher J. Easton
B.Sc. Flinders University; Ph.D. D.Sc., University of Adelaide, FAA

Chris Easton is a graduate of Flinders University and the University of Adelaide. He held positions at Harvard University (1980-1981), the Research School of Chemistry (1982), the University of Canterbury (1983-1986) and the University of Adelaide (1986-1994), before his appointment as a Senior Fellow in the Research School of Chemistry, in 1995.
He was awarded a D.Sc. from the University of Adelaide in 1998 and is the recipient of the Royal Australian Chemical Institute Birch Medal for 2000, and the Archibald Oll? Prize for Chemical Literature for 2000. He was promoted to Professor at the Research School of Chemistry in 2001 and elected as a Fellow of the Australian Academy of Science in 2004.  

Professor

PhD DSc (Adelaide), BSc (Flinders), FAA

chris.easton@anu.edu.au,

+61 2 61258201

ANU Researchers profile

1. 1. • 
   2. 

Chris Easton is a graduate of Flinders University and the University of Adelaide. He held positions at Harvard University (1980-1981), the Research School of Chemistry (1982), the University of Canterbury (1983-1986) and the University of Adelaide (1986-1994), before his appointment as a Senior Fellow in the Research School of Chemistry, in 1995.
He was awarded a D.Sc. from the University of Adelaide in 1998 and is the recipient of the Royal Australian Chemical Institute Birch Medal for 2000, and the Archibald Ollé Prize for Chemical Literature for 2000. He was promoted to Professor at the Research School of Chemistry in 2001 and elected as a Fellow of the Australian Academy of Science in 2004. He is also the Graduate Studies Convenor for Chemistry.

Areas of expertise

• Organic Chemical Synthesis
• Physical Organic Chemistry
• Polymerisation Mechanisms
• Characterisation Of Biological Macromolecules
• Nanochemistry And Supramolecular Chemistry
• Industrial Chemistry
• Free Radical Chemistry
• Proteins And Peptides
• Separation Science
• Environmental Biotechnology
• Medicinal And Biomolecular Chemistry
• Organic Chemistry
• Theoretical And Computational Chemistry
• Nanotechnology

Publications

• Balotra, S, Newman, J, Cowieson, N et al 2015, 'X-ray structure of the amidase domain of AtzF, the allophanate hydrolase from the cyanuric acid-mineralizing multienzyme complex', Applied and Environmental Microbiology, vol. 81, no. 2, pp. 470-480.
• Fraser, S & Easton, C 2015, 'Biosynthetic incorporation of fluorinated amino acids into peptides and proteins', Australian Journal of Chemistry, vol. 68, no. 1, pp. 9-12.
• Amos, R, Chan, B, Easton, C et al 2015, 'Hydrogen-atom abstraction from a model amino acid: dependence on the attacking radical', Journal of Physical Chemistry B, vol. 119, no. 3, pp. 783-788.
• Alissandratos, A, Kim, H & Easton, C 2014, 'Formate production through carbon dioxide hydrogenation with recombinant whole cell biocatalysts', Bioresource Technology, vol. 164, pp. 7-11.
• Amos, R, Heinroth, F, Chan, B et al 2014, 'Hydrogen from formic acid through its selective disproportionation over sodium germanate - a non-transition-metal catalysis system', Angewandte Chemie International Edition, vol. 53, no. 42, pp. 11275-11279.
• CONT.........https://researchers.anu.edu.au/researchers/easton-cj  

 

....................

Canberra Civic viewed from Mount Ainslie with Lake Burley Griffin and Mount Stromlo in the background.


CANBERRA 

 COCK WILL TEACH YOU

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Join me on Linkedin

Join me on Facebook FACEBOOK

Join me on twitter     

Join me on google plus Googleplus

 amcrasto@gmail.com