INADEQUATE experiment

Homonuclear correlation of nuclei of with low natural abundance, spin-echo sequence for scalar coupling evolution, DQF to suppress unwanted coherences, a double quantum frequency scaled dimension in 2D spectra 

Starting with the basic INADEQUATE experiments the simulation focuses on the inherent disadvantage of homonuclear correlation experiments on nuclei with low natural abundance. 

The first step in increasing the signal intensity in INADEQUATE experiments is to implement a polarization transfer step. The INEPT-INADEQUATE experiment [5.162] starts with the INEPT sequence creating antiphase coherence for the sensitive nucleus with a subsequent coherence transfer step before continuing the basic INADEQUATE experiment. In Check it 5 A. 3.2 the INEPT-IN ADEQUATE pulse sequence is created and the results compared with the unrefocused ID INADEQUATE experiment. 

2D INADEQUATE experiments are also possible and these type of experiments are unique in that the fl dimension does not correspond to single quantum coherence frequency but to a double quantum coherence frequency. These double quantum coherences are observed because homonuclear coupling and chemical shift evolve simultaneously during the dO period and can not be suppressed. In Check its 5.4.3.3 and 

4 two alternative 2D INADEQUATE experiments are demonstrated. Both reveal the same connectivities, but the second experiment displays a COSY like spectrum. 

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The one-dimensional variations of the INADEQUATE experiment suppress the intense... 

Figure 2.12. Two-dimensional (2D-)INADEQUATE diagram of 1-butanol (12) [ CDajzCO, 95% v/v, 25°C, 50 MHz, 128 scans, 128 experiments], (a) Contour plot with the AB systems of bonded C atoms on the horizontal axis (b) plots of the three AB systems of the molecule obtained from (a) (c) contour plot of the symmetrised INADEQUATE experiment showing the AB or AX systems of bonded C atoms in the HH COSY format (cross signals on the axes perpendicular to the diagonal)...

Figure 2.13. Symmetrised two-dimensional INADEQUATE experiment with isopinocampheol (2) [ CDshCO, 250 mg in 0.3 ml, 25 °C, 50 MHz, 256 scans and exp.], (a) Stacked plot of the section between 8c = 20.9 and 48.2 (b) complete contour plot with cross signal pairs labelled a-k for the 11 CC bonds of the molecule to facilitate the assignments sketched in formula 2...

If the amount of the sample is sufficient, then the carbon skeleton is best traced out from the two-dimensional INADEQUATE experiment. If the absolute configuration of particular C atoms is needed, the empirical applications of diastereotopism and chiral shift reagents are useful (Section 2.4). Anisotropic and ring current effects supply information about conformation and aromaticity (Section 2.5), and pH effects can indicate the site of protonation (problem 24). Temperature-dependent NMR spectra and C spin-lattice relaxation times (Section 2.6) provide insight into molecular dynamics (problems 13 and 14). 

The correlation signals of the INADEQUATE experiment directly build up the ring skeleton A of the compound. Elere characteristic C shifts (5c = 123.1, 137.6 148.9, 109.1) establish the existence and position of two double bonds and of one tetrahedral C-0 single bond (5c = 70.5). DEPT spectra for the analysis of the CH multiplicities become unnecessary, because the INADEQUATE plot itself gives the number of CC bonds that radiate from each C atom. 

The INADEQUATE experiment is a homonuclear NMR technique in which coupling satellites are detected after suppressing the stronger... 

A two-dimensional INADEQUATE experiment therefore requires a pulse sequence capable of producing the following four changes in the spin and energy states ... 

A line is then drawn vertically upward from F to satellite peak F. The mirror image partner of F, appearing on the same horizontal axis, is A, which establishes the connectivity of the C-2 quaternary carbon with the attached methyl carbon (8 24.3). The carbon-carbon connectivity assignments based on the 2D INADEQUATE experiment are presented around the structure. 

Carbon-Carbon Connectivity Assignment by 2D INADEQUATE Experiment... 

The 2D INADEQUATE spectrum and C-NMR data of 7-hydroxyfrulla-nolide are given. Determine the carbon-carbon connectivities, and subsequently build the entire carbon skeleton based on the 2D INADEQUATE experiment. 

SELINQUATE (Berger, 1988) is the selective ID counterpart of the 2D INADEQUATE experiment (Bax et al., 1980). The pulse sequence is shown in Fig. 7.4. Double-quantum coherences (DQC) are first excited in the usual manner, and then a selective pulse is applied to only one nucleus. This converts the DQC related to this nucleus into antiphase magnetization, which is refocused during the detection period. The experiment has not been used widely because of its low sensitivity, but it can be employed to solve a specific problem from the connectivity information. 

Figure 7.4 Pulse sequence for the SELINQUATE experiment, which is a selective INADEQUATE experiment. (Reprinted from Mag. Reson. Chem. 29, H. Kessler et at, 527, copyright (1991), with permission from John Wiley and Sons Limited, Baffins Lane, Chichester, Sussex P019 lUD, England.)...

Bardet, M. Robert, D. Lundquist, K. von Unge, S. Distribution of erythro and threo forms of different types of P-O-4 structures in aspen lignin by carbon-13 NMR using the 2D inadequate experiment. Magn. Reson. Chem. 1998, 36, 597-600. 

Table 5 Results from ID INADEQUATE experiment carried out on diester 2 Chemical shift (ppm) Assignment Coupling constants (Hz)...

We mentioned above that it is possible to carry out carbon-carbon correlation experiments using the 2D INADEQUATE procedure. There, as you may remember from the discussion of one-dimensional INADEQUATE, we have a very difficult problem to solve carbon-13 represents only 1.1% of the total carbon nuclei present in a sample. And in the INADEQUATE experiment we need to detect only those molecules containing two carbon nuclei which couple with one another, i.e. about 10"4 of the nuclei present at the same time we have to get rid of the signal coming from those molecules containing only one carbon-13 (the great majority) ... 

Practical constraints prevent this technique from living up to its potential, even in this, the era of the superconducting probe. Until sensitivity improves by at least another order of magnitude, the INADEQUATE experiment will remain just that - inadequate by name and by nature. 

The heteronucleus-detected INADEQUATE experiment, first reported in 1981 by Freeman and co-workers, is elegantly capable of establishing the identity of adjacent neighbour carbons via [fcc couplings.21-24 Major drawbacks of the INADEQUATE experiment are extreme insensitivity and prodigious sample requirements. To an extent, the sensitivity and... 

Figure 2 (A) Pulse sequence used to acquire the 1,1- and INADEQUATE experiments... 

In 2001, Knaack and co-workers56 reported an application of the INADEQUATE experiment in the course of synthesizing and characterizing a biologically active 2-[l-(4-chlorobenzyl)-lH-indol-3-yl]-2-oxo-N-pyri-din-4-yl acetamide (6). Treatment of l-(4-chlorobenzyl)-lH-indole with oxalyl chloride afforded the corresponding oxoacetyl chloride that was finally subjected to aminolysis with 4-aminopyridine to afford the final product of the reaction scheme, 6. Although the NMR data supported the N-benzyl structure, a 1,1-ADEQUATE spectrum was acquired to provide additional confirmation of the structure of 6. 

The elucidation of the structure of 5,6-dihydrolamellarin37 38 served as the development vehicle for the entire family of ADEQUATE experiments. Hence, this work also represented the first reported application of the INADEQUATE experiment. Two important 1ADEQUATE correlations were observed in the benzopyrone portion of the molecule and are shown by 28. The C19 resonance was correlated via three bonds to the C23 carbonyl. The C22 carbon was correlated via three bonds to the C3 quaternary carbon adjacent to the C23 carbonyl. 

Fig. 5a. Part of the spectra obtained with the ID multiple selective INADEQUATE experiment III applied to cembrene 3 dissolved in CDCI3. The spectra were obtained after appropriate processing, showing the responses in the olefinic and the aliphatic regions after selective inversion of carbons...

Fig. 5b. Comparison of the results obtained with the basic (left) and the multiple selective (right) INADEQUATE experiment. The signals of C-10, C-16, C-17 and C-18 are shown and are compared with the responses measured with the modified experiment after perturbation of C-15. Corresponding satellite signals are connected by horizontal lines.

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