It has been shown that single-crystal X-ray analysis and solution NMR spectroscopy are methods that unambiguously identify isomers of analyzed compounds. In the context of the controlled substances analysis, results obtained with these methods are crucial because, in the absence of an appropriate reference standard, this is not always possible using routinely used technics such as LC-MS and GC-MS.
3.2. NMR Spectra
Conclusion and findings regarding the structure of analyzed compounds based on X-ray analysis results were confirmed by interpretation of solution NMR spectroscopy data. 1H NMR spectra for all analyzed samples display one set of signals coming from the examined compound.
Protons of substituted phenyl rings give signals in a range characteristic for aromatic systems (7.1–8.3 ppm). Signals derived from substituents on the phenyl ring appeared in the spectra of Compounds 2
(methylene at 6.20 ppm) and 4
(methyl at 2.41 ppm). The proton attached to Cα
can be observed at 5.40 (4-CDC), 5.19 (MDPT), 5.52 (4F-PHP) and 5.19 (3-MEC). Broad peaks with the highest chemical shifts can be assigned to the N-H protons of analyzed compounds. In case of 1
, only one signal is observed (10.45 ppm and 10.21 ppm, respectively). For MDPT and 3-MEC two diastereotopic protons attached to the nitrogen atom yielded double broad singlets (δ = 9.38 and 8.47 for 2
; δ = 9.30 and 8.95 for 4
, Figure 11
and Figure 12
). Peaks attributed to the methyl group attached to Cα
can be observed at 1.49 ppm (Compounds 1
) and 1.45 ppm (4
). The n
-butyl side chain of 4F-PHP forms multiplets in the range of 2.14–0.74 ppm.
Each of the described compounds is characterized by different substituents on the nitrogen atom, which is also evident in the NMR spectra. In case of 4-CDC, one singlet attributed to two methyl groups can be observed at 2.85 ppm, whereas the signal from the tert-butyl substituent of MDPT is located at 1.28 ppm. The 3-MEC ethyl group gives a multiplet at 1.26 ppm (three protons attached to the terminal C atom) and two broad singlets (3.05 ppm and 2.93 ppm) can be assigned to diastereotopic methylene protons. Eight protons of the pyrrolidine ring (4F-PHP) correspond to signals at 3.61, 3.48, 3.23 and 3.05 (position 2 of the pyrrolidine ring) and a multiplet at 1.96 ppm (position 3 of pyrrolidine ring).
All resonances for analyzed compounds are listed below:
1H NMR (500 MHz, DMSO) δ: 10.45 (bs, 1H, N+H), 8.08–8.03 (m, 2H, ArH orto), 7.78–7.63 (m, 2H, ArH meta), 5.40 (q, J = 7.2 Hz, 1H, CαH), 2.85 (s, 6H, N(CH3)2), 1.49 (d, J = 7.2 Hz, 3H, CαH3).
13C NMR (126 MHz, DMSO) δ: 195.3 (C=O), 139.8 (Ar-para), 132.1 (Ar-Cipso), 130.8 (Ar-orto), 129.4 (Ar-meta), 64.0 (Cα), 42.0 (N(CH3)2), 13.5 (CH3)
1H NMR (500 MHz, DMSO) δ: 9.38 (bs, 1H, N+H2), 8.47 (bs, 1H, N+H2), 7.89 (dd, J = 8.3, 1.7 Hz, 1H, ArH-6), 7.71 (d, J = 1.7 Hz, 1H, ArH-4), 7.15 (d, J = 8.2 Hz, 1H, ArH-7), 6.20 (s, 2H, -O-CH2-O-), 5.23–5.15 (m, 1H, CαH), 1.49 (d, J = 5.8 Hz, 3H, CαCH3), 1.28 (s, 9H, C(CH3)3).
13C NMR (126 MHz, DMSO) δ: 194.4 (C=O), 153.1, (Ar-C1) 148.4 (Ar-C3), 126.6 (Ar-Cipso), 126.2 Ar-C6), 108.7 (Ar-C7), 108.2 (Ar-C4), 102.6 (O-CH2-O), 57.9 (C(CH3)3), 52.4 (Cα), 25.9 (C(CH3)3), 18.5 (CH3)
1H NMR (500 MHz, DMSO) δ 10.21 (bs, 1H, N+H), 8.21–8.15 (m, 2H, ArH, orto), 7.49 (t, J = 8.2 Hz, 2H, ArH, meta), 5.52 (bs, 1H, CαH), 3.67–3.56 (m, 1H, PRL-1), 3.54–3.43 (m, 1H, PRL-1), 3.23 (bs, 1H, PRL-1), 3.05 (bs, 1H, PRL-1), 2.14–2.02 (m, 1H, -CH2-CH2-CH2-), 2.02–1.85 (m, 4H, PRL-2, 1H, -CH2-CH2-CH2-), 1.27–1.11 (m, 3H, -CH2-CH2-CH2-), 1.05–0.91 (m, 1H, -CH2-CH2-CH2-), 0.74 (t, J = 6.8 Hz, 3H, CH3).
13C NMR (126 MHz, DMSO) δ: 195.2 (C=O), 166.5 (Ar-para), 132.2 (Ar-orto), 132.1 (Ar-Cipso), 116.5 (Ar-meta), 67.7 (Cα), 54.0 (PRL-C2), 51.9 (PRL-C2), 29.3 (PRL-C3), 25.5 (-CH2-), 22.8 (-CH2-), 21.8 (-CH2-), 13.4 (-CH3)
1H NMR (500 MHz, DMSO) δ 9.30 (bs, 1H, N+H2), 8.95 (bs, 1H, N+H2), 7.91–7.84 (m, 2H, ArH-2,4), 7.61–7.55 (m, 1H, ArH-6), 7.53–7.47 (m, 1H, ArH-5), 5.19 (bs, 1H, CαH), 3.05 (bs, 1H, N-CH2-C), 2.93 (bs, 1H, N-CH2-C), 2.41 (s, 3H, ArCH3), 1.45 (d, J = 7.1 Hz , 3H, CαCH3), 1.26 (t, J = 7.2 Hz, 3H, CH2CH3).
13C NMR (126 MHz, DMSO) δ: 196.5 (C=O), 138.8 (Ar-Cipso), 135.4 (Ar-C6), 132.9 (Ar-C3), 129.1 (Ar-C2, Ar-C5), 126.1 (Ar-C4), 56.7 (Cα), 40.3 (-CH2-), 20.8 (Ar-CH3), 15.7 (Cα-CH3)11.2 (-CH2-CH3)