Caryophyllene Oxide HMQC

The olefinic methylene group (protons and carbon) and the three methyl groups (protons and carbons) are trivial assignments, and they correspond with our previous discussion. Of more interest and of greater utility, we assign the three methine protons the doublet of doublets at 2.86 ppm (correlates with the carbon resonance at 63.0 ppm), the apparent quartet at 2.60 ppm (correlates with the carbon resonance at 48.0 ppm), and an apparent triplet at 1.76 ppm (correlates with the carbon resonance at 50.1 ppm). From the COSY and from the known structure, we now are now able to assign all three methine resonances and feed this information back into the COSY to establish other correlations. 

Beginning from the low-frequency end of the l3C spectrum, the following assignments can be made the methylene carbon at 26.6 ppm correlates with proton resonances at 1.45 and 1.63 ppm, the methylene carbon at 29.2 ppm correlates with proton resonances at 2.11 

FIGURE 5.15 The H, 13C, and DEPT spectra for caryophyllene oxide. The numbering for this structure is used in the text. 

FIGURE 5.16 The DQF COSY spectrum for caryophyllene oxide. The lower portion is an expanded view with correlation lines drawn in and assignments are given as an aid. 

FIGURE 5.17 The HMQC spectrum for caryophyllene oxide. In place of the usual l3C spectrum, the inset uses the DEPT 135 for better clarity. 

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The DQF-COSY spectrum of caryophyllene oxide can be found in Figure 5.16. The problem here is that there is no good entry point. The previous statement is not trivial. Without an entry point, it is impossible to relate the many obvious correlations (drawn in for convenience) that we see to a structural formula. Our approach therefore will be to record some of the correlations that we do see and wait until we have other information (i.e., HMQC) before we try to translate these correlations into a structure. 

This apparent conflict can be resolved by a close examination of the methyl singlets at about 0.98 ppm. There is an unusually low-frequency multiplet, partially buried by the methyl singlets, which we had initially overlooked. This type of unexpected dividend is common in correlation spectra both partially and completely obscured resonances usually reveal themselves in 2-D spectra (see HMQC below). Before continuing our discussion of caryophyllene oxide, let us consider H—13C correlations and how H— H correlations interplay with H—13C correlations. 

The COSY spectrum for caryophyllene oxide can be understood more clearly when interpreted in conjunction with the information from an HMQC spectrum (Figure 5.17). From the DEPT spectrum (see Figure 5.15), we already know that caryophyllene oxide has three methyl carbon resonances (16.4, 22.6, and 29.3 ppm), six methylene carbon resonances (26.6,29.2, 29.5, 38.4, 39.1, and 112.0 ppm), three methine carbon resonances (48.1, 50.1, and 63.0 ppm) and three quaternary carbon resonances (33.3,59.1, and 151.0 ppm)... 

H-l shows coupling to both C-2 protons at 1.45 and 1.63 ppm. The interaction is weak between H-l and H-2 at 1.63 ppm. Both C-2 protons are coupled to both C-3 protons at 0.95 and 2.06 ppm and the appropriate cross peaks can be found. Thus, we have shown indirect connectivities from C-10 through C-9, C-l, and C-2 all the way to C-3. The HMQC has been invaluable in our interpretation. However, many questions still remain. We neither have correlations to the three quaternary carbons nor to the three methyl groups. The HMQC and the COSY together support the structure for caryophyllene oxide, but they do not preclude other possible structures. 

The common theme so far in our correlation experiments has been to allow spins to evolve during q under the influence of directly coupled nuclear spins. We have seen the power of COSY, HMQC, HMBC, and INADEQUATE to provide us with detailed structural information for ipsenol, caryophyllene oxide, and lactose. In this section, we will develop another method for showing correlations and apply it to molecules with distinct, isolated proton spin systems such as carbohydrates, peptides, and nucleic acids. 

Compared to caryophyllene oxide and lactose, the HMQC spectrum for the tetra-peptide appears relatively simple (Figure 5.33). Indeed, VGSE has only 10 carbon atoms with attached protons and the spectrum shows correlations to nine carbons. Actually, there are 10 correlations as can be seen in the inset of the shielded methyl portion of the spectrum. Let us summarize the complementary information up to and including the HMQC spectrum. 

Chapter 5 still covers 2-D correlation but has been reorganized, expanded, and updated, which reflects the ever increasing importance of 2-D NMR. The reorganization places all of the spectra together for a given compound and treats each example separately ipsenol, caryophyllene oxide, lactose, and a tetrapeptide. Pulse sequences for most of the experiments are given. The expanded treatment also includes many new 2-D experiments such as ROESY and hybrid experiments such as HMQC-TOCSY. There are many new Student Exercises. 

FIGURE 6.18. The 300-MHz (F2) HMQC (also called inverse detected HETCOR ) spectrum of caryophyllene oxide. 

Before we tackle the HMBC for caryophyllene oxide, let us practice on ipsenol. The HMBC for ipsenol (Figure 6.19) looks like the HETCOR (with its axes switched) for ipsenol with two obvious differences There are considerably more correlations and the one-bond correlations (HMQC) are gone. Interpretation of HMBCs requires a degree of flexibility because we do not always find what we expect to find. In particular, whereas two-bond correlations (2/CH) are almost always found, the three-bond (3/CH) correlations are occasionally absent. The variations in correlations that we find result from the variations in the magnitude of 2Jni and VC coupling constants. 

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