6368 J. Am. Chem. Soc., Vol. 118, No. 27, 1996
Ohkata et al.
stirred overnight at room temperature. The resultant mixture was
filtered, and the filtrate was dried over MgSO4. After solvent removal,
the resultant solid was recrystallized from acetone to give 220 mg of
9a as a pure sample.
3H), 3.15 (s, 3H), 4.10 (s, 3H), 7.07 (s, 1H), 7.52 (t, J ) 6.2 Hz, 1H),
7.84 (d, J ) 8.4 Hz, 1H), 8.14 (t, J ) 8.4 Hz, 1H), 10.29 (d, J ) 6.2
Hz, 1H). The ratio of 14-N and 14-F is 9:1.
2,10,12-Trimethyl-6λ4-pyrido[1′′,2′′:2′,3′][1,2,4]-thiadiazolo[1′,5′:
1,5][1,2,4]thiadiazolo[2,3-a]pyridinium iodide (11a): 76% yield; mp
2,4-Dimethyl-6λ4-pyrido[1′′,2′′:2′,3′][1,2,4]-thiadiazolo[1′,5′:1,5]-
[1,2,4]thiadiazolo[2,3-a]pyrimidine (9a): 86% yield; mp 234-235 °C
(acetone); 1H NMR (CDCl3) δ 2.54 (s, 3H), 2.68 (s, 3H), 6.54 (s, 1H),
6.89 (ddd, J ) 8.1, 6.2, 1.8 Hz, 1H), 7.53 (dd, J ) 8.6, 1.8 Hz, 1H),
7.63 (ddd, J ) 8.6, 8.1, 1.5 Hz, 1H), 8.31 (dd, J ) 6.2, 1.5 Hz, 1H).
2,4,8-Trimethyl-6λ4-pyrido[1′′,2′′:2′,3′][1,2,4]-thiadiazolo[1′,5′:1,5]-
[1,2,4]thiadiazolo[2,3-a]pyrimidine (9b): 55% yield; mp 265 °C
(acetone); 1H NMR (CDCl3) δ 2.4-2.8 (bs, 6H), 2.74 (s, 3H), 6.53 (s,
1H), 6.69 (d, J ) 6.6 Hz, 1H), 7.44 (d, J ) 8.6 Hz, 1H), 7.62 (dd, J
) 8.6, 6.6 Hz, 1H).
1
285 °C dec; H NMR (CDCl3) δ 2.58 (s, 3H), 2.61 (s, 3H), 4.07 (s,
3H), 7.18 (d, J ) 6.3 Hz, 1H), 7.20 (d, J ) 5.4 Hz, 1H), 7.46 (s, 1H),
7.53 (s, 1H), 9.09 (d, J ) 5.4 Hz, 1H), 9.40 (d, J ) 6.3 Hz, 1H).
12-Ethoxycarbonylmethyl-2,10-dimethyl-6λ4-pyrido[1′′,2′′:2′,3′]-
[1,2,4]thiadiazolo[1′,5′:1,5][1,2,4]-thiadiazolo[2,3-a]pyridinium
1
iodide (11b): 88% yield; mp 225-226 °C; H NMR (CDCl3) δ 1.32
(t, J ) 7.2 Hz, 3H), 2.56 (s, 6H), 4.30 (q, J ) 7.2 Hz, 2H), 5.49 (s,
2H), 7.0-7.3 (m, 2H), 7.53 (bs, 2H), 8.90 (d, J ) 5.9 Hz, 1H), 9.37
(d, J ) 6.4 Hz, 1H).
2,4,10-Trimethyl-6λ4-pyrido[1′′,2′′:2′,3′][1,2,4]-thiadiazolo[1′,5′:
1,5][1,2,4]thiadiazolo[2,3-a]pyrimidine (9c): 83% yield; mp 235-
236 °C (acetone); 1H NMR (CDCl3) δ 2.41 (s, 3H), 2.52 (s, 3H), 2.65
(s, 3H), 6.51 (s, 1H), 6.71 (d, J ) 6.2 Hz, 1H), 7.31 (s, 1H), 8.14 (d,
J ) 6.2 Hz, 1H).
General Procedure for Preparation of 13-F and 14-N. A mixture
of 2-(methylamino)-4,6-dimethylpyrimidine (15, 120.3 mg, 0.88 mmol)
and 4,6-dimethyl-2-isothiocyanatopyrimidine 6a in chloroform (3 mL)
was heated at reflux temperature for 10 h. Removal of solvent gave
thiourea (175.4 mg). A mixture of the solid product (63.4 mg) and
NCS (26.7 mg, 0.20 mmol) in chloroform (4 mL) was stirred at room
temperature for 20 min. Filtration of the mixture afforded a solid
product. The solid was treated with KI to give 13-F.
9-Chloro-2,4-dimethyl-6λ4-pyrido[1′′,2′′:2′,3′][1,2,4]-thiadiazolo-
[1′,5′:1,5][1,2,4]thiadiazolo[2,3-a]pyrimidine (9d): 69% yield; mp >
300 °C (acetone); 1H NMR (CDCl3) δ 2.57 (s, 3H), 2.71 (s, 3H), 6.59
(s, 1H), 7.49 (d, J ) 9.1 Hz, 1H), 7.66 (dd, J ) 9.1, 2.2 Hz, 1H), 8.35
(d, J ) 2.2 Hz, 1H).
3-Chloro-2,4,8,10,12-pentamethyl-6λ4-pyrimido[1′′,2′′:2′,3′][1,2,4]-
thiadiazolo[1′,5′:1,5][1,2,4]-thiadiazolo[2,3-a]pyrimidinium iodide
1
2(or 4)-Methyl-6λ4-pyrido[1′′,2′′:2′,3′][1,2,4]-thiadiazolo[1′,5′:1,5]-
[1,2,4]thiadiazolo[2,3-a]pyrimidine (9e or 9e′): 90% yield; mp 246
(13-F): H NMR (CDCl3) δ 2.70 (s, 3H), 2.77 (s, 3H), 3.10 (s, 3H),
3.28 (s, 3H), 4.13 (s, 3H), 7.34 (s, 1H).
1
2,4,13-Trimethyl-6λ4-pyrido[1′′,2′′:2′,3′][1,2,4]-thiadiazolo[1′,5′:
°C (acetone); H NMR (CDCl3) δ 2.6-2.8 (3H), 6.5-6.8 (1H), 6.94
1
(dt, J ) 6.4, 1.8 Hz, 1H), 7.58 (d, J ) 8.6 Hz, 1H), 7.73 (ddd, J ) 8.6,
6.4, 1.5 Hz, 1H), 8.29 (d, J ) 6.4 Hz, 1H), 8.3-8.7 (1H), at 10 °C δ
[2.62 (s), 2.77 (s), 3H], [6.69 (d, J ) 4.8 Hz) 6.77 (d, J ) 4.8 Hz),
1H], 6.96 (dt, J ) 6.4, 1.5 Hz, 1H), 7.58 (d, J ) 8.8 Hz, 1H), 7.70
(ddd, J ) 8.8, 6.4, 1.5 Hz, 1H), 8.36 (d, 6.4 Hz, 1H), [8.43 (d, J ) 4.8
Hz), 8.69 (d, J ) 4.8 Hz).
1,5][1,2,4]thiadiazolo[2,3-a]pyrimidinium iodide (14-N): H NMR
(CDCl3) δ 2.64 (s, 3H), 3.15 (s, 3H), 4.10 (s, 3H), 7.07 (s, 1H), 7.52
(t, J ) 6.2 Hz, 1H), 7.84 (d, J ) 8.4 Hz, 1H), 8.14 (t, J ) 8.4 Hz, 1H),
10.29 (d, J ) 6.2 Hz, 1H).
Preparation of 12-d6 from Deuterated 2-Methylamino-4,6-di-
methylpyrimidine (15-d6). To deuterium oxide (5 mL) was slowly
added 94.2 mg of NaH (62.3% in oil). To the resultant aqueous NaOD
solution was added 15 (113.4 mg, 0.83 mmol), and the solution was
heated at reflux temperature for 1 h. The deuterated compound was
extracted into ether, and the organic layers were concentrated to give
109.4 mg of 15-d6. Deuterated 10-S-3 sulfurane 12-d6 was prepared
by a similar procedure to that used in the preparation of 13-F. The 1H
NMR spectrum of the sample in D2O indicated that two methyl groups
at 8,10-positions of 12 were 95%-enriched: 1H NMR (CDCl3) for 12-
d6 δ 2.73 (s, 3H), 3.03, 3.20 (d, J ) 0.66 Hz, 3H), 4.11 (s, 3H), 7.16
(s, 1H), 7.30 (s, 1H).
2,4-Dimethyl-6λ4-thiadiazolo[3′′,2′′:2′,3′][1,2,4]-thiadiazolo[1′,5′:
1,5][1,2,4]thiadiazolo[2,3-a]pyrimidine (9f): 76% yield; mp 235-238
1
°C (acetone); H NMR (CDCl3) δ 2.58 (s, 3H), 2.70 (s, 3H), 6.61 (s,
1H), 6.85 (d, J ) 4.0 Hz, 1H), 7.51 (d, J ) 4.0 Hz, 1H).
2,10-Dimethyl-6λ4-pyrido[1′′,2′′:2′,3′][1,2,4]-thiadiazolo[1′,5′:1,5]-
[1,2,4]thiadiazolo[2,3-a]pyridine (10): 90% yield; mp 240-241 °C
1
(CH2Cl2-acetone); H NMR (CDCl3) δ 2.39 (s, 6H), 6.69 (dd, J )
6.2, 1.3 Hz, 2H), 7.24 (d, J ) 1.3 Hz, 2H), 8.13 (d, J ) 6.2 Hz, 2H);
13C NMR (CDCl3) δ 21.39, 115.47, 117.68, 132.88, 148.76, 156.02,
168.01.
General Procedure for Alkylation of the 10-S-3 Sulfurane 8a,
8d, 9a, and 10. To a solution of 8a (112.2 mg, 0.39 mmol) in
dichloromethane (20 mL) was added methyl iodide (223.5 mg, 1.57
mmol), and the mixture was heated at reflux temperature for 13 h.
Concentration of the mixture afforded a solid product. Recrystallization
of the solid from dichloromethane-n-hexane gave a pure sample of
12.
2,4,8,10,12-Pentamethyl-6λ4-pyrimido[1′′,2′′:2′,3′][1,2,4]thiadia-
zolo[1′,5′:1,5][1,2,4]-thiadiazolo[2,3-a]pyrimidinium iodide (12): 78%
yield; mp 242-245 °C dec; 1H NMR (CDCl3) δ 2.65 (s, 3H), 2.73 (s,
3H), 3.03 (d, J ) 0.65 Hz, 3H), 3.23 (d, J ) 0.66 Hz, 3H), 4.11 (s,
3H), 7.16 (q, J ) 0.65 Hz, 1H), 7.30 (q, J ) 0.66 Hz, 1H); 13C NMR
(acetone-d6) δ 20.42, 20.53, 25.27, 25.67, 33.96, 117.44, 118.17, 153.85,
157.73, 159.82, 163.97, 167.28, 174.85, 176.15.
3-Chloro-2,4,8,10,12-pentamethyl-6λ4-pyrimido[1′′,2′′:2′,3′][1,2,4]-
thiadiazolo[1′,5′:1,5][1,2,4]-thiadiazolo[2,3-a]pyrimidinium iodide
(13-F) and 3-chloro-2,4,8,10,13-pentamethyl-6λ4-pyrimido[1′′,2′′:
2′,3′][1,2,4]-thiadiazolo[1′,5′:1,5][1,2,4]thiadiazolo[2,3-a]pyrimidin-
ium iodide (13-N): 99% yield. For 13-F: 1H NMR (CDCl3) δ 2.70
(s, 3H), 2.77 (s, 3H), 3.10 (s, 3H), 3.28 (s, 3H), 4.13 (s, 3H), 7.34 (s,
1H). For 13-N: 1H NMR (CDCl3) δ 2.77 (s, 3H), 2.83 (s, 3H), 3.13
(s, 3H), 3.28 (s, 3H), 4.13 (s, 3H), 7.22 (s, 1H). The ratio of 13-N and
13-F was 2:1.
2,4,12-Trimethyl-6λ4-pyrido[1′′,2′′:2′,3′][1,2,4]-thiadiazolo[1′,5′:
1,5][1,2,4]thiadiazolo[2,3-a]pyrimidinium iodide (14-F) and 2,4,13-
trimethyl-6λ4-pyrido[1′′,2′′:2′,3′][1,2,4]-thiadiazolo[1′,5′:1,5][1,2,4]-
thiadiazolo[2,3-a]pyrimidinium iodide (14-N): 53% yield. For 14-
F: 1H NMR (CDCl3) δ 2.74 (s, 3H), 3.26 (s, 3H), 4.16 (s, 3H), 7.58
(t, J ) 6.0 Hz, 1H), 7.70 (t, J ) 8.6 Hz, 1H), 8.26 (t, J ) 8.6 Hz, 1H),
9.82 (d, J ) 6.0 Hz, 1H). For 14-N: 1H NMR (CDCl3) δ 2.64 (s,
N,N ′-Di(4,6-dimethyl-2-pyrimidinyl)-N,N ′-dimethylthiourea (16).
To a mixture of 2-(methylamino)-4,6-dimethylpyrimidine (15, 1.31 g,
9.6 mmol) and sodium hydrogen carbonate (880 mg, 10 mmol) in 55
mL of acetonitrile was added thiophosgene (0.37 mL, 4.9 mmol), and
the mixture was heated at reflux temperature for 12.5 h. The mixture
was poured into water, and the product was extracted into dichlo-
romethane. The organic layers were dried over Na2SO4 and concen-
trated to leave a solid residue. Column chromatographic separation of
the solid on silica gel (n-hexane:ethyl acetate ) 2:1) afforded 16.
Recrystallization from methanol gave 16 as a pure sample: 43%
1
yield: mp 168-170 °C; H NMR (CDCl3) δ 2.15 (s, 12H), 3.83 (s,
6H), 6.26 (s, 2H).
2,4,8,10,12,13-Hexamethyl-6λ4-pyrimido[1′′,2′′:2′,3′][1,2,4]-thia-
diazolo[1′,5′:1,5][1,2,4]-thiadiazolo[2,3-a]pyrimidinium Di(triiodide)
(17). A mixture of 16 (53.4 mg, 0.17 mmol) and iodine (129 mg,
0.51 mmol) in dichloromethane (20 mL) was stirred for 30 min at room
temperature to afford precipitates. The resultant precipitates were
obtained by filtration and recrystallized from acetonitrile to give 180
1
mg (99%) of 17: mp 156-157 °C dec; H NMR (CD3CN) δ 2.83 (s,
6H), 2.99 (s, 6H), 4.57 (s, 6H), 7.66 (s, 2H); 13C NMR (acetone-d6) δ
19.77, 25.97, 40.07, 122.45, 151.40, 162.05, 178.31, 210.46; UV (CH3-
CN) λmax nm (ꢀ) 362 (49 400), 292 (106 000), 238 (29 400).
General Procedure for Preparation of 18a,b via 19a,b, 20a,b,
and 21a,b. A mixture of N-ethylaniline (2.0 g, 19 mmol) and 4,6-
dimethyl-2-isothiocyanatopyrimidine (6a, 1.5 g, 9 mmol) in 10 mL of
acetonitrile was stirred at room temperature for 20 h. The mixture
was filtered, and the solid was recrystallized from methanol to give a
pure sample 19 (550 mg) in 97% yield. To a solution of 19 (50 mg,
0.17 mmol) in dichloromethane (3 mL) was added SO2Cl2 (0.015 mL,
0.19 mmol) at 0 °C. After stirring overnight, 140 mg (1.7 mmol) of