1-Adamantyl cation – Predicting its NMR spectra

1-Adamantyl cation – Predicting its NMR spectra

What is required in order to compute very accurate NMR chemical shifts? Harding, Gauss and Schleyer take on the interesting spectrum of 1-adamantyl cation to try to discern the important factors in computing its ¹³C and ¹H chemical shifts.¹

1

To start, the chemical shifts of 1-adamtyl cation were computed at B3LYP/def2-QZVPP and
MP2/qz2p//MP2/cc-pVTZ. The root means square error (compared to experiment) for the carbon chemical shifts is large: 12.76 for B3LYP and 6.69 for MP2. The proton shifts are predicted much more accurately with an RMS error of 0.27 and 0.19 ppm, respectively.

The authors speculate that the underlying cause of the poor prediction is the geometry of the molecule. The structure of 1 was optimized at HF/cc-pVTZ, MP2/cc-pVTZ and CCSD(T)/pVTZ and then the chemical shifts were computed using MP2/tzp with each optimized geometry. The RMS error of the ¹²C chemical shifts are HF/cc-pVTZ: 9.55, MP2/cc-pVTZ: 5.62, and CCSD(T)/pVTZ: 5.06. Similar relationship is seen in the proton chemical shifts. Thus, a better geometry does seem to matter. The CCSD(T)/pVTZ optimized structure of 1 is shown in Figure 1.

1

Figure 1. CCSD(T)/pVTZ optimized structure of 1.

Unfortunately, the computed chemical shifts at CCSD(T)/qz2p//CCSD(T)/cc-pVTZ are still in error; the RMS is 4.78ppm for the carbon shifts and 0.26ppm for the proton shifts. Including a correction for the zero-point vibrational effects and adjusting to a temperature of 193 K to match the experiment does reduce the error; now the RMS for the carbon shifts is 3.85 ppm, with the maximum error of 6 ppm for C3. The RMS for the proton chemical shifts is 0.21ppm.

The remaining error they attribute to basis set incompleteness in the NMR computation, a low level treatment of the zero-point vibrational effects (which were computed at HF/tz2p), neglect of the solvent, and use of a reference in the experiment that was not dissolved in the same media as the adamantyl cation.

So, to answer our opening question – it appears that a very good geometry and treatment of vibrational effects is critical to accurate NMR shift computation of this intriguing molecule. Let the
computational chemist beware!

References

(1) Harding, M. E.; Gauss, J.; Schleyer, P. v. R., "Why Benchmark-Quality Computations Are Needed To Reproduce 1-Adamantyl Cation NMR Chemical Shifts Accurately," J. Phys. Chem. A, 2011, 115, 2340-2344, DOI: 10.1021/jp1103356

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Welwitindolinones structure

A quick note here on the use of computed NMR to determine stereochemical structure. The Garg group synthesized two “oxidized welwitindolines”, compounds 1 and 2.¹ The relative stereochemistry at the C3 position (the carbon with the hydroxy group) was unknown.

1

2

Low energy gas-phase conformers of both epimers of 1 and 2 were optimized at B3LYP/6-31+G(d,p). (These computations were done by the Tantillo group.) See Figure 1 for the optimized lowest energy conformers. Using these geometries the NMR chemical shifts were computed at mPW1PW91/6-311+G(d,p) with implicit solvent (chloroform). The chemical shifts were Boltzmann-weighted and scaled according to the prescription (see this post) of Jain, Bally and Rablen.² The computed chemical shifts were then compared against the experimental NMR spectra. For both 1and 2, the ¹³C NMR shifts could not readily distinguish the two epimers. However, the computed ¹H chemical shifts for the S epimer of each compound was significantly in better agreement with the experimental values; the mean average deviation for the S epimer of 2 is 0.08 ppm but 0.36ppm for the R epimer. As a check of these results, DP4 analysis³ (see this post) of 2 indicated a 100% probability for the S epimer using only the proton chemical shifts or with the combination of proton and carbon data.

1

2

Figure 1. B3LYP/6-31+G(d,p) optimized geometries of the
lowest energy conformations of 1 and 2.

References

(1) Quasdorf, K. W.; Huters, A. D.; Lodewyk, M. W.; Tantillo, D. J.; Garg, N. K., "Total Synthesis of Oxidized Welwitindolinones and (-)-N-Methylwelwitindolinone C Isonitrile," J. Am. Chem. Soc. 2011,134, 1396-1399, DOI: 10.1021/ja210837b

(2) Jain, R.; Bally, T.; Rablen, P. R., "Calculating Accurate Proton Chemical Shifts of Organic Molecules with Density Functional Methods and Modest Basis Sets," J. Org. Chem. 2009, 74, 4017-4023, DOI: 10.1021/jo900482q.

(3) Smith, S. G.; Goodman, J. M., "Assigning Stereochemistry to Single Diastereoisomers by GIAO NMR Calculation: The DP4 Probability," J. Am. Chem. Soc. 2010, 132, 12946-12959, DOI:10.1021/ja105035r

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Spectrum for Neostigmine

Neostigmine shows notable UV/VIS absorption at 261nm, 267nm, and 225nm.

Neostigmine's ¹H NMR Spectroscopy reveals shifts at: 7.8, 7.7, 7.4, 7.4, 3.8, and 3.1 parts per million. The higher shifts are due to the aromatic hydrogens. The lower shifts at 3.8ppm and 3.1ppm are due to the electronic withdrawing nature of the tertiary and quarterary nitrogen, respectively.

pnmr of neostigime

13c nmr


HMBC SPECTRUM


IR

Neostigmine, N,N,N-trimethyl-meta-(dimethylcarbomoyloxy)-phenylammonium methylsulfonate, which can be viewed as a simplified analog of physostigmine, is made by reacting 3-dimethylaminophenol with N-dimethylcarbamoyl chloride, which forms the dimethylcarbamate, and its subsequent alkylation using dimethylsulfate forming the desired compound. 

• 43. J.A. Aeschlimann, U.S. Patent 1,905,990 (1933).

Spectral data[

Neostigmine shows notable UV/VIS absorption at 261 nm, 267 nm, and 225 nm.^[7]

Neostigmine's ¹H NMR Spectroscopy reveals shifts at: 7.8, 7.7, 7.4, 7.4, 3.8, and 3.1 parts per million. The higher shifts are due to the aromatic hydrogens. The lower shifts at 3.8ppm and 3.1ppm are due to the electronic withdrawing nature of the tertiary and quarterary nitrogen, respectively.^[8]

1. Porst H; Kny L (May 1985). "[The structure of degradation products of neostigmine bromide]". Pharmazie. (in German) 40 (5): 325–8. PMID 4034636.
2. Jump up^ Ferdous, Abu J; Waigh, Roger D (1993). "Application of the WATR technique for water suppression in 1H NMR spectroscopy in determination of the kinetics of hydrolysis of neostigmine bromide in aqueous solution". Journal of Pharmacy and Pharmacology 45 (6): 559–562. doi:10.1111/j.2042-7158.1993.tb05598.x. PMID 8103105

BAHRAIN

 
 


 


 
 

 

 

 

 

 

 
 
 
 

 
 
 



 

 

 
 

 
 


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Take a tour











 Qantab beach in oman
 
 Stephen Rego

 
 


 

 

 


 
 


 

 

 

A lovely day at the beach my sis and I spent at Qantab back in 2006:

(I have a thing for old Mosques).

Yeah, walking on that roof was soooooo not a good idea (I was covered in dust when a section caved in). Alhamdulilah I wasn't hurt at all, and was a little mroe willing to take advice about what is structurally sound and what isn't.

Our fave midnight hang-out ledge. For loosing Ah's fishing rods.

 Other than that, carry on!

Omani architecture

Muscat Fashion Week

enjoying art and eye candy

fabulous food and places to see and be seen

fabulous finds

Castles and Jinn

Omani traditions and superstitions

camping and off-road adventures

desert sunrises

not desert, and not just Salalah

recipes, Omani and inspired by Oman

forts crumbling into ruins and castles in the clouds

Mountain villages

coastal villages

the simple life

the simple life

and a couple of camels of course!

and a couple of camels of course!.............http://howtolivelikeanomaniprincess.blogspot.in/2011/06/my-own-photos-qantab-beach-2006.html

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