3.2. Synthesis of 4-Arylmethyl (Z)-N′-(Adamantan-1-yl)-Morpholine-4-Carbothioimidates 7a–e and 4-Arylmethyl (Z)-N′-(Adamantan-1-yl)-4-Phenylpiperazine-1-Carbothioimidates 8a–e
The appropriate arylmethyl bromide (2 mmol) and anhydrous potassium carbonate (276 mg, 2 mmol) were added to a solution of N-(adamantan-1-yl)morpholine-4-carbothioamide 5 (560 mg, 2 mmol) or N-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioamide 6 (711 mg, 2 mmol), in anhydrous acetone (15 mL), and the mixture was heated under reflux for 4 h. The solvent was then distilled off in vacuo and the resulting residues were washed with water (20 mL), dried, and crystallized from ethanol or aqueous ethanol.
Benzyl (Z)-N′-(adamantan-1-yl)-morpholine-4-carbothioimidate 7a: 1H-NMR: δ 1.61–1.66 (m, 6H, adamantane-H), 1.85 (m, 6H, adamantane-H), 2.0 (s, 3H, adamantane-H), 3.20–3.21 (m, 4H, morpholine-H), 3.65–3.72 (m, 4H, morpholine-H), 3.90 (s, 2H, benzylic CH2), 7.07–7.19 (m, 5H, Ar-H). 13C-NMR: δ 29.02, 29.80, 35.96, 54.18 (adamantane-C), 37.06 (benzylic CH2), 49.66, 66.42 (morpholine-C), 125.60, 126.44, 127.90, 140.02 (Ar-C), 154.46 (C=N). ESI-MS, m/z: 372.3 (M + H)+.
4-Chlorobenzyl (Z)-N′-(adamantan-1-yl)-morpholine-4-carbothioimidate 7b: 1H-NMR: δ 1.62–1.65 (m, 6H, adamantane-H), 1.69–1.72 (m, 6H, adamantane-H), 2.05–2.06 (m, 3H, adamantane-H), 3.99 (s, 2H, benzylic CH2), 3.20–3.22 (m, 4H, morpholine-H), 3.65–3.72 (m, 4H, morpholine-H), 6.99 (d, 2H, Ar-H, J = 7.5 Hz), 7.14 (d, 2H, Ar-H, J = 7.5 Hz). 13C-NMR: δ 29.26, 29.99, 35.98, 54.08 (adamantane-C), 36.98 (benzylic CH2), 48.60, 66.44 (morpholine-C), 127.65, 128.65, 133.0, 138.04 (Ar-C), 154.24 (C=N). ESI-MS, m/z (Rel. Int.): 405.4 (M + H, 100)+, 407.4 (M + 2 + H, 35)+.
4-Bromobenzyl (Z)-N′-(adamantan-1-yl)-morpholine-4-carbothioimidate 7c: 1H-NMR: δ 1.63–1.69 (m, 6H, adamantane-H), 1.84 (m, 6H, adamantane-H), 2.01 (s, 3H, adamantane-H), 3.25–3.30 (m, 4H, morpholine-H), 3.69–3.74 (m, 4H, morpholine-H), 3.91 (s, 2H, benzylic CH2), 7.17 (d, 2H, Ar-H, J = 7.5 Hz), 7.45 (d, 2H, Ar-H, J = 7.5 Hz). 13C-NMR: δ 29.59, 29.94, 36.57, 54.69 (adamantane-C), 37.76 (benzylic CH2), 49.70, 66.85 (morpholine-C), 121.0, 130.51, 137.26, 146.91 (Ar-C), 156.46 (C=N). ESI-MS, m/z (Rel. Int.): 449.4 (M + 2 + H, 100)+, 451.4 (M + 2 + H, 98)+.
4-Nitrobenzyl (Z)-N′-(adamantan-1-yl)-morpholine-4-carbothioimidate 7d: 1H-NMR: δ 1.62 (s, 6H, adamantane-H), 1.77–1.79 (m, 6H, adamantane-H), 1.98–2.0 (m, 3H, adamantane-H), 3.24–3.30 (m, 4H, morpholine-H), 3.69–3.72 (m, 4H, morpholine-H), 4.02 (s, 2H, benzylic CH2), 7.42 (d, 2H, Ar-H, J = 8.2 Hz), 8.21 (d, 2H, Ar-H, J = 8.2 Hz). 13C-NMR: δ 29.58, 29.84, 36.44, 54.79 (adamantane-C), 37.53 (benzylic CH2), 49.79, 66.78 (morpholine-C), 123.76, 129.64, 146.07, 146.91 (Ar-C), 156.71 (C=N). ESI-MS, m/z: 416.2 (M + H)+.
3,5-Bis(trifluoromethyl)benzyl (Z)-N′-(adamantan-1-yl)-morpholine-4-carbothioimidate 7e: 1H-NMR: δ 1.53–1.56 (m, 12H, adamantane-H), 1.85–1.87 (m, 3H, adamantane-H), 3.10–3.12 (m, 4H, morpholine-H), 3.68–3.70 (m, 4H, morpholine-H), 4.17 (s, 2H, benzylic CH2), 7.95 (s, 1H, Ar-H), 8.0 (s, 2H, Ar-H). 13C-NMR: δ 29.16, 29.66, 35.25, 54.85 (adamantane-C), 36.41 (benzylic CH2), 49.76, 66.20 (morpholine-C), 120.76, 122.72, 130.39, 142.78 (Ar-C), 124.89 (CF3), 148.37 (C=N). ESI-MS, m/z: 507.2 (M + H)+.
Benzyl (Z)-N′-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidate 8a: 1H-NMR: δ 1.69 (s, 6H, adamantane-H), 1.74 (s, 6H, adamantane-H), 2.0 (s, 3H, adamantane-H), 2.88–2.92 (m, 4H, piperazine-H), 3.02–3.06 (m, 4H, piperazine-H), 3.98 (s, 2H, benzylic CH2), 6.84–7.04 (m, 5H, Ar-H), 7.12–7.16 (m, 5H, Ar-H). 13C-NMR: δ 29.10, 29.96, 35.68, 53.98 (adamantane-C), 46.90, 48.18 (piperazine-C), 36.90 (benzylic CH2), 114.28, 119.90, 126.92, 128.24, 129.0, 130.58, 139.94, 149.26 (Ar-C), 152.0 (C=N). ESI-MS, m/z: 446.3 (M + H)+.
4-Chlorobenzyl (Z)-N′-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidate 8b: 1H-NMR: δ 1.71–1.76 (m, 12H, adamantane-H), 2.15–2.17 (m, 3H, adamantane-H), 2.63–2.65 (m, 4H, piperazine-H), 3.22–3.24 (m, 4H, piperazine-H), 3.98 (s, 2H, benzylic CH2), 6.89–6.91 (m, 3H, Ar-H), 6.95–6.96 (m, 2H, Ar-H), 7.29–733 (m, 4H, Ar-H). 13C-NMR: δ 29.17, 29.71, 35.51, 53.07 (adamantane-C), 48.65, 48.10 (piperazine-C), 36.39 (benzylic CH2), 115.55, 116.13, 119.89, 128.49, 129.16, 129.45, 130.57, 150.31 (Ar-C), 151.27 (C=N). ESI-MS, m/z (Rel. Int.): 380.2 (M + H, 100)+, 382.2 (M + 2 + H, 37)+.
4-Bromobenzyl (Z)-N′-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidate 8c:
1H-NMR: δ 1.65 (s, 6H, adamantane-H), 1.86 (s, 6H, adamantane-H), 2.02–2.03 (m, 3H, adamantane-H), 3.26–3.27 (m, 4H, piperazine-H), 3.43–3.44 (m, 4H, piperazine-H), 3.95 (s, 2H, benzylic CH
2), 6.92–7.93 (m, 1H, Ar-H), 7.00–7.01 (m, 2H, Ar-H), 7.18 (d, 2H, Ar-H,
J = 7.0 Hz), 7.29–7.33 (m, 2H, Ar-H), 7.44 (d, 2H, Ar-H,
J = 7.0 Hz).
13C-NMR: δ 29.95, 36.58, 42.98, 54.70 (adamantane-C), 48.96, 49.17 (piperazine-C), 37.77 (benzylic CH
2), 116.20, 119.97, 120.94, 129.22, 130.59, 131.54, 137.33, 149.26 (Ar-C), 151.29 (C=N). ESI-MS,
m/z (Rel. Int.): 524.4 (M + H, 98)
+, 526.4 (M + 2 + H, 100)
+ [
38].
4-Nitrobenzyl (Z)-N′-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidate 8d: 1H-NMR: δ 1.53 (s, 6H, adamantane-H), 1.72 (s, 6H, adamantane-H), 1.91 (s, 3H, adamantane-H), 3.16–3.18 (m, 4H, piperazine-H), 3.30–3.33 (m, 4H, piperazine-H), 3.97 (s, 2H, benzylic CH2), 6.80–6.89 (m, 3H, Ar-H), 7.18–7.29 (m, 2H, Ar-H), 7.36 (d, 2H, Ar-H, J = 8.0 Hz), 8.08 (d, 2H, Ar-H, J = 8.0 Hz). 13C-NMR: δ 29.65, 29.90, 36.52, 54.86 (adamantane-C), 37.54 (benzylic CH2), 43.03, 49.12 (piperazine-C), 116.21, 120.05, 123.72, 129.21, 129.66, 146.14, 146.94, 148.09 (Ar-C), 151.22 (C=N). ESI-MS, m/z: 491.2 (M + H)+.
3,5-Bis(trifluoromethyl)benzyl (Z)-N′-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidate 8e: 1H-NMR: δ 1.58 (s, 6H, adamantane-H), 1.69 (s, 6H, adamantane-H), 1.95–1.97 (m, 3H, adamantane-H), 3.29–3.31 (m, 4H, piperazine-H), 3.40–3.42 (m, 4H, piperazine-H), 4.04 (s, 2H, benzylic CH2), 6.93–7.02 (m, 3H, Ar-H), 7.29 (s, 1H, Ar-H), 7.32–7.34 (m, 2H, Ar-H), 7.78 (s, 2H, Ar-H). 13C-NMR: δ 29.80, 35.51, 36.44, 54.80 (adamantane-C), 37.31 (benzylic CH2), 49.0, 49.13 (piperazine-C), 116.28, 120.12, 129.16, 129.24, 131.44, 131.63, 141.30, 147.50 (Ar-C), 124.04 (CF3), 151.19 (C=N). ESI-MS, m/z: 582.2 (M + H)+.