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DOI: 10.1055/s-2003-43342
Synthesis and Reactivity of 3,4-Dimethyl-4H-1,3,4-thiadiazines
Publikationsverlauf
Publikationsdatum:
21. November 2003 (online)
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Abstract
3,4-Dimethyl-4H-1,3,4-thiadiazines, novel 8π heterocyclic systems, were prepared by cyclization of α-haloketones with 1,2,4-trialkylthiosemicarbazides. The desulfurization of the products afforded 5-imino-1,2-dimethylpyrazoles by valence isomerization into thia-σ-homopyrazoles.
Key words
cyclizations - heterocycles - sulfur - synthetic methodology - valence isomerization
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References
Typical Procedure for the Synthesis of 2-Alkylamino-3,4-dimethyl-5-aryl-2,3-dihydro-4 H -1,3,4-thiadiazines (3). An EtOH solution (20 mL) of 1,2-dimethyl-4-iso-propylthiosemicarbazide (1a) (1.47 g, 10.0 mmol) or of 1,2,4-trimethylthiosemicarbazide (1b) (1.19 g 10.0 mmol) and of the corresponding phenacyl bromide 2 (10.0 mmol) was refluxed for 1 h. After cooling to 20 °C, Et2O was added to give a colourless precipitate. The latter was isolated by filtration and recrystallized from EtOH-Et2O with addition of HBr. 3a: Yield: 2.20 g (70%); colourless lamella (EtOH-Et2O); mp 160-161 °C. IR (KBr): 705 (m), 712 (m), 781 (m), 820 (m), 970 (m), 1030 (m), 1170 (m), 1311 (s), 1410 (m), 1460 (s), 1499 (s), 1610 (s), 2995 (m), 3110 (m), 3225 (s) cm-1. 1H NMR (300 MHz, DMSO-d 6): δ =3.22 (br s, 1 H, NH+), 3.36 (d, 3 H, NHMe+), 3.75 (s, 3 H, NMe) 4.18 (s, 3 H, NMe), 6.26 (s, 1 H, 6-H), 7.32-7.66 (m, 5 H, ArH). 13C NMR (75 MHz, DMSO-d 6): δ = 30.14 (NMe), 32.52 (NMe), 43.99 (NMe), 121.78 (6-C), 124.38 (CH, Ar), 128.65 (CH, Ar), 129.90 (CH, Ar), 130.92 (Ar), 150.58 (5-C), 152.50 (2-C). MS (EI, 70 eV): m/z = 234 (17) [M+], 233 (11), 231 (9), 220 (31), 218 (43), 202 (23), 201 (29), 187 (48), 186 (16), 118 (23), 96 (92), 94 (100). Anal. Calcd for C12H16N3BrS (314.25): C, 45.87; H, 5.13; N, 13.37. Found: C, 45.79; H, 4.56; N, 13.08. All products gave satisfactory spectroscopic and analytical data.
111,2-Dimethyl-3-phenyl-5-methyliminopyrazoline-hydrate hydrobromide (4). Method A: A solution of 3a (3.14 g, 10.0 mmol) in HBr acid (15 mL, 48%) was refluxed for 1 h. After refluxing for 4-5 min sulfur started to precipiate. The solvent was evaporated under reduced pressure. The residue was recrystallized from EtOH-Et2O to give 4 as colourless lamella (1.20 g, 40%), mp 168 °C. The compound crystallized as a hydrate and hydrobromide. The water could not be completely removed in vacuo over P4O10 (140 °C). Method B: A solution of 3a (3.14 g, 10.0 mmol) in HCl acid (15 mL, concentrated) was refluxed for 1 h. The work up was carried out as described for method A. Yield: 0.90 g, 30%. Method C: A solution of 3a (3.14 g, 10.0 mmol) in glacial HOAc (10 mL) was refluxed 1 h. The mixture was poured into Et2O (150 mL). A colourless precipitate was formed. The latter was filtered off and recrystallized from EtOH-Et2O to give 4 as a colourless solid (1.60 g, 53%). IR (KBr): 780 (s), 805 (m), 812 (m), 924 (w), 989 (w), 1045 (m), 1082 (m), 1203 (w), 1295 (m) 1302 (m), 1430 (s), 1480 (s), 1496 (m), 1542 (m), 1645 (s), 2920 (m), 2951 (m), 3098 (s), 3225 (s) cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.78 (br s, 1 H, NH+), 2.99-3.01 (d, 3 H, NHMe+), 3.71-3.78 (d, 3 H, NHMe+), 4.24 (s, 3 H, NMe), 5.74 (s, 1 H, 4-H), 7.45-7.59 (s, 5 H, ArH), 8.40 (br s, 1 H, NH+). 13C NMR (75 MHz, CDCl3): δ = 30.31 (NMe), 34.74 (NMe), 35.11 (NMe), 89.53 (CH, Hetar), 126.89 (CH, Ar), 128.8 (CH, Ar), 129.49 (CH, Ar), 131.34 (Ar), 152.10 (3-C), 153.72 (5-C). MS (EI, 70 eV): m/z = 234 (4) [M+], 219 (4), 201 (11), 188 (100), 172 (10), 145 (16), 102 (48). Anal. Calcd for C12H18N3O (300.20): C, 48.01; H, 6.04; N, 13.98. Found: C, 48.20; H, 6.20; N, 13.98.