Aromatic protons

Polar solvents shift the keto enol equilibrium toward the enol form (174b). Thus the NMR spectrum in DMSO of 2-phenyl-A-2-thiazoline-4-one is composed of three main signals +10.7 ppm (enolic proton). 7.7 ppm (aromatic protons), and 6.2 ppm (olefinic proton) associated with the enol form and a small signal associated with less than 10% of the keto form. In acetone, equal amounts of keto and enol forms were found (104). In general, a-methylene protons of keto forms appear at approximately 3.5 to 4.3 ppm as an AB spectra or a singlet (386, 419). A coupling constant, Jab - 15.5 Hz, has been reported for 2-[(S-carboxymethyl)thioimidyl]-A-2-thiazoline-4-one 175 (Scheme 92) (419). This high J b value could be of some help in the discussion on the structure of 178 (p. 423). 

The —OH proton of a primary alcohol RCH2OH is vicinal to two protons and its sig nal would be expected to be split into a triplet Under certain conditions signal splitting of alcohol protons is observed but usually it is not Figure 13 21 presents the NMR spec trum of benzyl alcohol showing the methylene and hydroxyl protons as singlets at 8 4 7 and 2 5 respectively (The aromatic protons also appear as a singlet but that is because they all accidentally have the same chemical shift and so cannot split each other)... 

The exchange of aromatic protons can be effected in the absence of any -OH or —NH2 activating group during the course of a Clemmensen reduction in deuteriochloric and deuterioacetic acid mixture (see section Ill-D). This reaction has been carried out with various tricyclic diterpenes and is best illustrated by the conversion of dehydroabietic acid into its 12,14-d2-labeled analog (40 -+ 41).Amalgamated zinc is reportedly necessary for the exchange reaction since the results are less satisfactory when a zinc chloride-mercuric chloride mixture is used. 

A solution of estradiol (38, 15 mg) in methanol-OD (4 ml) and one drop of 10% deuteriosulfuric acid in deuterium oxide is heated under reflux for 5 days. After cooling the reaction mixture is diluted with ether, washed with dilute sodium bicarbonate solution and water, then dried over anhydrous sodium sulfate. Evaporation of the ether gives crystalline 2,4-d2-estradiol (39, 15 mg, 99%), mp 173-175° (ether-hexane), exhibiting 82% isotopic purity and only one aromatic hydrogen by NMR. (For an experimental procedure describing the exchange of aromatic protons under Clemmensen conditions, see section III-D.)... 

After completion of the reaction, the mixture is diluted with water, extracted with ether and the residue from the ether phase purified by chromatography and/or recrystallization. If the substrate contains aromatic protons, the reduction procedure is repeated in protic medium to back exchange deuteriums incorporated into the aromatic ring. 

Extensions of the enamine alkylation to a-tetralones have also been used (245-248), but product yields were lower, presumably due to steric crowding in a transition state where generation of an imonium salt gives rise to a repulsion between a methylene group on nitrogen and a peri aromatic proton. 

Activating group Hammett cr value Deshielding of aromatic proton value (5) Ref. 

I The five aromatic proton signals (black in Figure 13.19) overlap into a complex pattern with a large peak at 7.42 8 and a broad absorption at 7.57 8. 

Much of the difference in chemical shift between aromatic protons (6.5-8.0 8) and vinylic protons (4.5-6.5 5) is clue to a property of aromatic... 

Figure 15.14 The origin of aromatic ring-current. Aromatic protons are deshielded by the induced magnetic field caused by delocalized tt electrons circulating in the molecular orbitals of the aromatic ring.

The Md NMR spectrum of /)-bromotoluene, shown in Figure 15.15, displays many of the features just discussed. The aromatic protons appear as two doublets at 7.02 and 7.45 8, and the benzylic methyl protons absorb as a sharp singlet at 2.29 8. Integration of the spectrum shows the expected 2 2 3 ratio of peak areas. 

H1 NMR spectroscopy was found to be unsuitable for head-group analysis of HSi-PaM-eSt. The resonance associated with the Si-H proton at the head-group is broadened by multiple splitting and the resonances of the aromatic protons of the initiator fragment are buried in the aromatic proton resonances of phenyl rings of the aMeSt repeating units. 

Resonances associated with the aromatic protons and the Si-H proton in the HSKCHj Q C CHt- head-group, respectively, appear at 6.5-7.0 and 3.5-4.0 ppm. 

Significantly, integration of aromatic protons/Si-H head-group per polymer and demonstrates survival of this bond during polymerization. 

The submitters report obtaining the product in 99% yield. The enantiomeric excess of the Mosher ester of 3 was measured to be 98% using a Chiralcel OD column (40% 2-propanol/hexane). This optical purity measurement substantiated the optical purity assessment made by 111 NMR studies of 3 and racemic 3 prepared using a different method3. Addition of the chiral shift reagent tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorato]europium (III) resulted in clear resolution of the respective aromatic proton signals for the two enantiomers, which was demonstrated with the racemate. Under similar conditions, NMR analysis of 3 showed that within the detectable limits of the experiment (ca. <3%), there was none of the disfavored enantiomer. 

Mass spectra of compounds 11 are characterized by the presence of fission products of the molecule tricyclic moiety (m/e of fragments depending on alkaloid type) and ergolene moiety with m/e 448 and after SO2 elimination m/e 384 = 448 -SO2. The characteristic IH-NMR is the absence of signal for C - 2 proton and a new multiplet at region 7-7.5 ppm for aromatic protons from saccharin moiety. 

The COSY-45° spectrum of vasicinone displays two distinct spin systems, as indicated by square brackets. Cross-peaks A-H represent coupling between five relatively upfield protons cross-peaks I-K are due to couplings between the aromatic protons. We start from the most down-field proton of the upfield spin system, resonating at 8 5.10, and trace all the other coupling interactions. For instance, the peak at 8 5.10... 

I, however, represent the only long-range interactions between C-5a and /3 protons, and C-3 proton in the spin system (ring C). The down-field second spin system is represented by cross-peaks K-M due to the aromatic protons. Even the most downfield C-8 proton (8 8.25) is seen to show a strong cross-peak L with the C-11 proton (8 7.72), a feature characteristic of HOHAHA spectra. The HOHAHA interactions are presented on the structure. 

The most downfield cross-peaks, V-Y, are due to heteronuclear couplings of the aromadc or vinylic protons and carbons. For instance, cross-peak Y represents heteronuclear interaction between the C-1 vinylic proton (8 5.56) and a carbon resonating at 8 134.0 (C-1). The downfield cross-peaks, V and W, are due to the heteronuclear correlations of the ortho and meta protons (8 7.34 and 7.71) in the aromatic moiety with the carbons resonating at 8 128.3 and 126.9, respectively. The remaining cross-peak X is due to the one-bond correlation of the C-4 aromatic proton (8 7.42) with the C-4 carbon appearing at 8 131.4. The cross-peak U displays direct H/ C connectivity between the carbon at 8 77.9 (C-6) and C-6 methine proton (8 4.70). The crosspeak T is due to the one-bond heteronuclear correlation of carbon... 

The HMQC spectrum of podophyllotoxin shows heteronuclear crosspeaks for all 13 protonated carbons. Each cross-peak represents a one-bond correlation between the C nucleus and the attached proton. It also allows us to identify the pairs of geminally coupled protons, since both protons display cross-peaks with the same carbon. For instance, peaks A and B represent the one-bond correlations between protons at 8 4.10 and 4.50 with the carbon at 8 71.0 and thus represent a methylene group (C-15). Cross-peak D is due to the heteronuclear correlation between the C-4 proton at 8 4.70 and the carbon at 8 72.0, assignable to the oxygen-bearing benzylic C-4. Heteronuclear shift correlations between the aromatic protons and carbons are easily distinguishable as cross-peaks J-L, while I represents C/H interactions between the methylenedioxy protons (8 5.90) and the carbon at 8 101.5. The C-NMR and H-NMR chemical shift assignments based on the HMQC cross-peaks are summarized on the structure. 

Other major peaks in the H-NMR spectrum were a six-proton singlet at 8 2.03 assigned to the N(CH5)2 protons and groups of three- and two-proton multiplets centered at 8 7.50 and 7.85 due to the aromatic protons of the benzamidic moiety substituted on C-3 of ring A. 

The shifts produced by the addition of a paramagnetic complex have been used in the assignment of the aromatic protons in (83). ... 

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