high field nmr experiments in the upper level laboratory courses at furman university l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
High-Field NMR Experiments in the Upper-Level Laboratory Courses at Furman University PowerPoint Presentation
Download Presentation
High-Field NMR Experiments in the Upper-Level Laboratory Courses at Furman University

Loading in 2 Seconds...

play fullscreen
1 / 36

High-Field NMR Experiments in the Upper-Level Laboratory Courses at Furman University - PowerPoint PPT Presentation


  • 149 Views
  • Uploaded on

High-Field NMR Experiments in the Upper-Level Laboratory Courses at Furman University . Tim Hanks, Moses Lee and Larry Trzupek Dept. of Chemistry, Furman University. Current NMR Instrumentation. Varian EM-360A (1981; $31,000) CW; H-1 only

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'High-Field NMR Experiments in the Upper-Level Laboratory Courses at Furman University' - miliani


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
high field nmr experiments in the upper level laboratory courses at furman university

High-Field NMR Experiments in the Upper-Level Laboratory Courses at Furman University

Tim Hanks, Moses Lee and

Larry Trzupek

Dept. of Chemistry, Furman University

current nmr instrumentation

Current NMR Instrumentation

Varian EM-360A (1981; $31,000) CW; H-1 only

Varian VXR-300S (1988; $329,000) FT; H-1/C-13 and multinuclear; VT; computer system updated to Sun SPARCstation 5 in 1996

Varian Inova 500 (1996; $454,000) FT; indirect detection probe, H-1 {N-15/P-31}; VT; Sun SPARC station 5 computer system.

enantioselective epoxidation hanks chem 23

Enantioselective Epoxidation (Hanks; Chem 23)

NMR Techniques:

- H-1 NMR analysis of fructose-based intermediates,

-methylstyrene, and epoxide product

- C-13 NMR analysis of the chiral catalyst and epoxide

product

- use of chiral lanthanide shift reagent for determination

of enantiomeric purity

enantioselective epoxidation hanks chem 238

Enantioselective Epoxidation (Hanks; Chem 23)

H-1 NMR analysis, trans--methylstyrene, vinyl region

6.6 6.4 6.2

enantioselective epoxidation hanks chem 239

Enantioselective Epoxidation (Hanks; Chem 23)

C-13 NMR analysis, chiral oxirane precursor

180 140 100 60 20 ppm

enantioselective epoxidation hanks chem 2310

Enantioselective Epoxidation (Hanks; Chem 23)

NMR determination of enantiomeric purity using Eu(hfc)3

4.8 4.4 4.0 3.6 3.2 ppm

enantioselective epoxidation hanks chem 2311

Enantioselective Epoxidation (Hanks; Chem 23)

NMR determination of enantiomeric purity; results

Typical yield of epoxide product: 60%

Typical enantiomeric excess: 84%ee

Reference: “Catalytic Asymmetric Epoxidation Using a

Fructose-Derived Catalyst”; Andy Burke,

Patrick Dillon, Kyle Martin and Tim Hanks,

J. Chem. Ed., accepted for publication, 1999.

structure of a tricyclic compound lee chem 23

Features:

- Microscale preparation

- Multi-step reaction sequence

- Use of basic 2-D NMR to establish structure

Initial Reactants:

cyclopentadiene, maleic anhydride

Target Compound:

endo-9-methoxycarbonyl-3-oxatricyclo[4,2,1,0]-2-nonane

Structure of a Tricyclic Compound (Lee; Chem 23)

structure of a tricyclic compound lee chem 2313

Structure of a Tricyclic Compound (Lee; Chem 23)

(yield: 40 - 70%)

References: W. J. Shepard, J. Chem. Ed., 40, 40-41 (1963);

L. F. Fieser and K. L. Williamson, Organic Experiments, 7th ed., D. C. Heath, pp. 283-294 (1992)

structure of a tricyclic compound lee chem 2314

Structure of a Tricyclic Compound (Lee; Chem 23)

COSY spectrum of tricyclic product

Reference: “The Microscale Synthesis and the Structure Determination of Endo-9-methoxycar-

bonyl-3-oxatricyclo[4,2,1,0]-2-nonane”; M. Lee, J. Chem. Ed., 69, A172-A173 (1992)

detailed nmr characterization trzupek chem 34

Goals:

to develop

- a basic understanding of 2D NMR methods

- the ability to carry out 2D experiments independently

- the ability to process 2D data productively

- a facility with the interpretation of such data

Requirements:

assignment of

- all H-1 resonances (chemical shift, mulitplet pattern)

- all C-13 resonances (chemical shift)

- all H-H coupling constant values

- all C-H coupling constant values

Detailed NMR Characterization (Trzupek; Chem 34)

detailed nmr characterization trzupek chem 3416

NMR Techniques Available:

- simple H-1 spectrum

- resolution-enhanced H-1 spectrum

- proton decoupled H-1 spectrum

- use of lanthanide shift reagents

- relay COSY

- multiple quantum filtered COSY

- homonuclear 2D-J

- simple C-13 spectrum

- heteronuclear 2D-J

- HETCOR

-spectral simulation (H-1)

Detailed NMR Characterization (Trzupek; Chem 34)

detailed nmr characterization trzupek chem 3417

Sample requirements:

- ready availability (commercial or easily prepared)

- good purity, solubility

- overlapping proton resonances

- complex splitting patterns

- manageable molecular size (5 to 8 types of H’s)

Typical candidates:

Detailed NMR Characterization (Trzupek; Chem 34)

(5-hexen-2-one)

(3,4-pentadien-1-ol)

(8-hydroxyquinoline)

detailed nmr characterization trzupek chem 3424

Results, 5-hexene-2-one: student report sheet

Detailed NMR Characterization (Trzupek; Chem 34)

Hchemshift multiplet J(x,y) J(x,y) J(x,y)

A 5.04 tdd AB, 2.2 AC, 17.0 AD, 1.1

B 4.97 tdd AB, 2.2 BC, 10.4 BD, 1.4

C 5.82 ddt AC, 17.0 BC, 10.4 CD, 6.6

D 2.33 tddd BD, 1.4 CD, 6.6 DE, 7.4

E 2.55 t DE, 7.4

F 2.16 s

Cchem shiftJ(H)

a 114.9 160 (A,B)

c 136.7 156 (C)

d 27.5 122 (D,D)

e 42.5 124 (E,E)

f 29.7 128 (F,F,F)

g 207.8 ---

(all chemical shifts in ppm; all J values in Hz)

B

C

c

a

e

E

A

d

D

F

g

f

3d structure of aztmp by nmr lee chem 44

Background:

- bioactivation of AZT:

AZT ---1---> AZTMP ---2----> AZTDP ---3---> AZTTP

- reaction rate of step 2 (thymidylate kinase) - v. slow

- consequence: build-up of AZTMP; imbalance in the

nucleoside pool (the basis of AZT toxicity)

Goal:

- to determine if the solution conformation of AZTMP is

significantly different from that of AMP and if that dif-

ference might be the basis for the sluggish kinase reaction

3D structure of AZTMP by NMR (Lee; Chem 44)

3d structure of aztmp by nmr lee chem 4426

NMR techniques employed:

- H-1 spectrum

- P-31 spectrum

- COSY analysis

- homonuclear decoupling

(use of the above to assign proton chemical shifts and ob-

tain H-H coupling constants throughout the molecule)

- determination of T1 relaxation time values for each H

- acquisition of NOE difference spectra

(use of the above to obtain non-bonded distances between

selected protons in the molecule)

3D structure of AZTMP by NMR (Lee; Chem 44)

3d structure of aztmp by nmr lee chem 4427

3D structure of AZTMP by NMR (Lee; Chem 44)

AZTMP; H-1 spectrum in buffer (20:1 D2O/DMSO-D6)

(DMSO-d5)

5’

1’

4’

3’

2’

(HOD)

T-H6

H1’

T-CH3

8

6

4

2 ppm

3d structure of aztmp by nmr lee chem 4429

3D structure of AZTMP by NMR (Lee; Chem 44)

J-values by homonuclear decoupling

5’

H-2’

1’

4’

3’

H-2”

2’

H-2”

H-2’

Decoouple

At H-3’

========>

2.40 2.36 // 2.24 2.20 ppm

2.40 2.36 // 2.24 2.20 ppm

3d structure of aztmp by nmr lee chem 4430

3D structure of AZTMP by NMR (Lee; Chem 44)

Dihedral angles from the Karplus relationship

H-H couplingJ (Hz)degrees

1’-2’ 7.0 136

1’-2” 7.0 20

2’-3’ 5.5 30

2”-3’ 5.5 130

3’-4’ 3.7 128

4’-5’ 2.2 57

4’-5” 2.9 53

5’-5” 14.0 ---

5’-P 6.1 ---

5”-P 4.6 --

5’

1’

4’

3’

2’

3d structure of aztmp by nmr lee chem 4431

3D structure of AZTMP by NMR (Lee; Chem 44)

Additional conformational features from the J-values

5’

1’

4’

3’

2’

3d structure of aztmp by nmr lee chem 4434

Determination of the glycosidic torsional angle, 

3D structure of AZTMP by NMR (Lee; Chem 44)

- obtain NOE’s for irradiation at thymine H-6

- use known H-6/CH3 distance, NOE,

and T1 to obtain molecular correla-

tion time, c

- use c thus determined, other NOE’s,

and other T1’s to get other distances

3d structure of aztmp by nmr lee chem 4435

Results: solution-phase conformational structure of AZTMP

3D structure of AZTMP by NMR (Lee; Chem 44)

Comparison to structure of TMP: very similar; conclusion:

some other factor (steric bulk of azido group) responsible

for poor interaction with the thymidylate kinase.

M. Lee, J. Chem. Ed., 73, 184-187 (1996)

acknowledgments

Acknowledgments

- National Science Foundation

- Keck Foundation

- Milliken Foundation

- Furman Chemistry Alumni

- Furman University