Complete assignment of 1 H and 13 C NMR spectra of 1 , 2 , 4-trisubstituted pyrroles

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We describe here the spectral assignment containing a subjective analysis of the chemical shis for these pyrroles.We report the complete assignment of each of their 1 H and 13 C NMR spectra.

Spectra.
All NMR spectra were recorded in CDCl 3 at room temperature on either a Bruker AC-200 or a Bruker Avance-300 instrument using 5 mm sample tubes.All samples were freshly dissolved in CDCl 3 (0.6 mL).Chemical shis () in ppm are reported as quoted relative to the residual signals of chloroform ( 1 H, 7.26 ppm; 13 C, 77.16 ppm).Multiplicities are described as: s (singlet), bs (broad singlet), d (doublet), t (triplet), q (quartet), and m (multiplet); coupling constants (J) are reported in Hertz (Hz). 13C NMR spectra were recorded with total proton decoupling.e complete assignment of each 1 H and 13 C NMR chemical shi for these pyrroles was achieved by 1D and 2D NMR techniques, including APT experiments, 1 H-1 H COSY, 1 H-13 C Hetcor exp, and HMBC spectra.
1 H NMR spectra were recorded at a proton frequency of 300.13 MHz with a spectral width of 4 kHz with 32 K data points, using a 90 ∘ pulse and repetition time of 3 s.e 13 C NMR spectra were obtained with a pulse angle     of 90 ∘ , an acquisition time of 1.3 s and a sweep width of 220 ppm.e pulse repetition time was 3 s.Exponential multiplication was applied before the Fourier transformation in both cases.
A typical proton-proton Cosy experiment at 200 MHz was performed at a spectral width of 2000 Hz in the F 2 domain and 2000 Hz in the F 1 domain.Spectra were acquired with 1 K data points in F 2 with eight transients, two dummy scans and 256 experiments.
A typical carbon-proton correlated 2D spectrum at 50 MHz (or 75 MHz) was acquired with a spectral width of 14000 Hz in the F 2 domain and 1000 Hz (2000 Hz) in the F 1 domain.Spectra were acquired with 1 K data points in F 2 and 256 W in F 1 with 64 transients (two dummy scans) over 128 experiments.e delay between scans was 2 s.
e APT experiment was run with 90 ∘ and 180 ∘ pulse widths of 21 and 42 s in the 10 mm probe and 35 and 70 s in the 12 mm probe, respectively.A 7.1 ms delay corresponding to 1/J(CH) provided positive signals for quaternary (C) and methylene (CH 2 ) resonance and negative intensities for methine (CH) and methyl (CH 3 ) resonance.
e long-range 1 H- 13 C correlation (HMBC) spectra were obtained using the following sequence: spectra resulted from a 256 × 2048 data matrix with 16 scans per t 1 increment.Spectral widths of 3.5 kHz in f 2 and 16.7 kHz in f 1 were used.e acquisition time was 0.30 s, the delays were set at 3.45 ms (1/ 2 J(C,H)) and 65 ms (corresponding to an average 1/  J(C,H) of 7.7 Hz) and the recycle time was 1.44 s.Fourier transformation was performed on a 2 K × 1 K data matrix.

Results and Discussion
e structures and numbering schemes for 1,2,4trisubstituted pyrroles 1a-f, 2a-b, 3, 4, and 5a-b are shown in Figure 1.e 1 H and 13 C assignments for each pyrrole are given in Tables 1 and 2, respectively.e twelve pyrroles are systematically related to each other by changes occurring with the R 1 , R 2 , or R substituents.As shown in Figure 1, there were four different substituents R 1 (benzyl, butyl, phenyl, or allyl: series 1 and 2, 3, 4, and 5, resp.), two types of substituent R (H or alkyl) which led to two types of function (carboxylic acid or ester, series 1, 3, 4, and 5 or 2, resp.).e nature of substituent R 2 in position 2 varied greatly: phenyl, pentyl, ether, diester, thiol, and even -ionone, which led to pyrrole retinoid 2b.
e carbon type (C, CH, CH 2 , CH 3 ) was determined using an APT experiment.Assignment of each protonated carbon was performed by 2D heteronuclear-correlated experiments using delay values that corresponded to 1 J(CH).
H-6 and H-8 appearing as singlets and the nonprotonated carbons C-2 and C-4 were assigned using delays in the 2D experiment to emphasize the long range coupling (HMBC), with either 2 J(C,H) or 3 J(C,H) between the carbons and protons.
Attribution of the aromatic carbon for compounds 1a-f and 2a-b was performed through protons H-10 and H-14 appearing as a doublet which, using the 2D heteronuclearcorrelated experiments with delay values that corresponded to 1 J(CH), correlated with the up�eld methine aromatic carbon resonance (C-10) and (C-14).
For all phenyl substituents the aromatic carbons were attributed using delays in the 2D experiment to emphasize the long range coupling (HMBC), with either 2 J(C,H) or 3 J(C,H) between the carbons and protons.
Assignment of protons and carbons of saturated chains was determined using the multiplicity of the proton signals, their coupling constant, a typical proton-proton Cosy experiment and heteronuclear-correlated experiments using delay values that corresponded to 1 J(CH).
Concerning compound 2b, the nonprotonated carbons C-18 and C-22 were assigned using delays in the 2D experiment to emphasize the long range coupling (HMBC), with either 2 J(C,H) or 3 J(C,H) between the carbons and protons.