2ꢀHydroxyethyl methyleneꢀbisꢀtriazene oxides
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 11, November, 2015 2709
solution was diluted with EtOAc. The precipitate was collected
by filtration, washed with diethyl ether (2×100 mL), and dried
in vacuo to give the title product 1h in the yield of 18.3 g (58%).
1H NMR (D2O), δ: 2.70 (s, 3 H, CH3N); 3.00 (t, 2 H, CH2N,
J = 5.0 Hz); 3.50 (t, 2 H, CH2O, J = 5.0 Hz).
Synthesis of thio derivatives 2f,h (general procedure). To
a suspension of K2CO3 (0.01 mol) and NaI (0.001 mol) in DMF
(5 mL) cooled to 0 °C, chloromethyl methyl sulfide (0.025 mol)
was added dropwise with stirring. The reaction mixture was
stirred at 0 °C for 10 min, then the corresponding salt 1f,h
(0.02 mol) was added. The cooling was removed and the reacꢀ
tion mixture was stirred 8 h, diluted with ethyl acetate (60 mL),
and washed with water (3×20 mL). The organic layer was dried
and the solvent was removed in vacuo. Preparative TLC of the
residue afforded the target compounds 2f,h.
1ꢀ[(Methylthio)methoxy]ꢀ3,3ꢀpentamethyleneꢀ1ꢀtriazene 2ꢀ
oxide (2f)12. Preparative TLC (elution with MeOH—CHCl3,
1 : 15) afforded the title product in the yield of 25%. Oil. IR
(neat), ν/cm–1: 2942, 2856, 1497, 1443, 1223, 981. 1H NMR
(CDCl3), δ: 1.50 (m, 2 H, CH2(4)); 1.75 (m, 4 H, C(3)H2,
C(5)H2); 2.30 (s, 3 H, CH3S); 3.40 (t, 4 H, C(2)H2, C(6)H2,
J = 5.5 Hz); 5.25 (s, 2 H, CH2S).
ν/cm–1: 3474, 2963, 2883, 1490, 1275, 1025, 936. 1H NMR
(CDCl3), δ: 1.95 (m, 4 H, 2 CH2); 2.30 (br.s, 1 H, OH), 3.12
(s, 3 H, NCH3); 3.51, 3.72 (both t, 2 H each, 2 CH2, J = 5.0 Hz);
3.60 (t, 4 H, 2 CH2, J = 6.5 Hz); 5.74 (s, 2 H, OCH2O). 14N NMR
(CDCl3), δ: –50.54, –53.24. MS (ESI), m/z: 279.1423 [M + H]+,
296.1688 [M + NH4]+, 301.1244 [M + Na]+, 317.0976 [M + K]+.
C8H18N6O5. Calculated: 279.1411 [M
[M + NH4]+, 301.1231 [M + Na]+, 317.0970 [M + K]+.
Compounds 4a—g,h were synthesized similarly.
+
H]+, 296.1677
2,10ꢀDimethylꢀ5,7ꢀdioxaꢀ2,3,4,8,9,10ꢀhexaazadodecaꢀ3,8ꢀ
dienꢀ12ꢀol 3,9ꢀdioxide (4a). Yield 20%. Oil. IR (neat), ν/cm–1
:
1
3477, 2920, 1498, 1265, 1024, 939. H NMR (CDCl3), δ: 3.10
(s, 6 H, N(CH3)2); 3.15 (s, 3 H, NCH3); 3.55 (t, 2 H, HOCH2,
J = 5.0 Hz); 3.80 (t, 2 H, NCH2, J = 5.0 Hz); 5.70 (s, 2 H,
OCH2O). 14N NMR (CDCl3), δ: –49.62. MS (ESI), m/z:
253.1259 [M + H]+; 275.1083 [M + Na]+; 291.0825 [M + K]+.
C6H16N6O5. Calculated: 253.1255 [M + H]+; 275.1074 [M + Na]+,
291.0814 [M + K]+.
11ꢀEthylꢀ3ꢀmethylꢀ6,8ꢀdioxaꢀ3,4,5,9,10,11ꢀhexaazatridecaꢀ
4,9ꢀdienꢀ1ꢀol 4,10ꢀdioxide (4b). Yield 9%. Oil. IR (neat), ν/cm–1
:
3484, 2978, 2939, 2878, 1499, 1463, 1390, 1243, 1068, 1026,
1
947. H NMR (CDCl3), δ: 1.10 (t, 6 H, 2 CH3C, J = 7.1 Hz);
3ꢀ(2ꢀHydroxyethyl)ꢀ3ꢀmethylꢀ1ꢀ[(methylthio)methoxy]ꢀ1ꢀ
triazene 2ꢀoxide (2h). Preparative TLC (elution with MeOH—
CHCl3, 1 : 20) afforded the title product in the yield of 39%. IR
(neat), ν/cm–1: 3437, 2926, 1496, 1440, 1389, 1255, 1095, 1053,
981, 693. 1H NMR (CDCl3), δ: 2.25 (s, 4 H, OH and CH3S);
3.10 (s, 3 H, CH3N); 3.45 (t, 2 H, CH2, J = 5.0 Hz); 3.80 (t, 2 H,
CH2, J = 5.0 Hz); 5.75 (s, 2 H, CH2).
Synthesis of chloromethoxyꢀ1ꢀtriazene 2ꢀoxides 3f,h (general
procedure). To a stirred solution of the corresponding sulfide 2
(0.02 mol) in dichloromethane (40 mL), SO2Cl2 (2.83 g, 0.021 mol)
was added dropwise at 0 °C. After warming up to room temperaꢀ
ture, the reaction mixture was kept for 1 h. The solvent was
removed in vacuo, purification of the residue by preparative TLC
(elution with MeOH—CHCl3, 1 : 25) afforded the title prodꢀ
ucts 3f,h.
1ꢀChloromethoxyꢀ3,3ꢀ(pentamethylene)ꢀ1ꢀtriazene 2ꢀoxide
(3f)12. Yield 96%. Oil. IR (neat), ν/cm–1: 2946, 2857, 1499,
1445, 1323, 1227, 1086, 1018, 937, 918, 688. 1H NMR (CDCl3),
δ: 1.50 (m, 2 H, C(4)H2); 1.75 (m, 4 H, C(3)H2, C(5)H2); 3.50
(t, 4 H, C(2)H2, C(6)H2, J = 5.5 Hz); 5.85 (s, 2 H, CH2Cl).
3ꢀ(Chloroethyl)ꢀ1ꢀchloromethoxyꢀ3ꢀmethylꢀ1ꢀtriazene 2ꢀoxꢀ
ide (3h). Yield 85%. Oil. IR (neat), ν/cm–1: 2975, 2928, 1502,
1440, 1321, 1254, 1078, 1023, 941, 681. 1H NMR (CDCl3),
δ: 3.20 (s, 3 H, CH3N); 3.80 (m, 4 H, 2 CH2); 5.90 (s, 2 H, CH2).
MS (ESI), m/z: 202.0156 [M + H]+, 223.9967 [M + Na]+,
239.9706 [M + K]+. C4H9Cl2N3O2. Calculated: 202.0145
[M + H]+, 223.9964 [M + Na]+, 239.9703 [M + K]+.
3ꢀMethylꢀ10ꢀ(pyrrolidinꢀ1ꢀyl)ꢀ6,8ꢀdioxaꢀ3,4,5,9,10ꢀpenꢀ
taazadecaꢀ4,9ꢀdienꢀ1ꢀol 4,10ꢀdioxide (4e). To a suspension of
Naꢀsalt 1h (0.152 g, 0.97 mmol) and Na2CO3 (0.103 g,
0.97 mmol) in DMF (2 mL) cooled to 0 °C, a solution of chloꢀ
ride 3e (0.174 g, 0.97 mmol) in DMF (1 mL) was added. The
reaction mixture was stirred at 20 °C for 7 h, kept at room temꢀ
perature for 16 h, diluted with water (10 mL), and extracted with
ethyl acetate (4×5 mL). The combined organic layers were
washed with water (3×1 mL), dried with MgSO4, and the solvent
was removed in vacuo. Purification of the residue by preparative
TLC (elution with ethyl acetate—hexane, 2 : 1) afforded comꢀ
pound 4e in the yield of 0.081 g (30%), viscous oil. IR (neat),
2.40 (br.s, 1 H, OH); 3.10 (s, 3 H, CH3N); 3.20 (q, 4 H,
2 CCH2N, J = 7.1 Hz); 3.50 (t, 2 H, CH2, J = 5.0 Hz); 3.75 (t, 2 H,
CH2, J = 5.0 Hz); 5.80 (s, 2 H, OCH2O). 14N NMR (CDCl3),
δ: –54.63. MS (ESI), m/z: 303.1394 [M + Na]+, 319.1129
[M + K]+. C8H20N6O5. Calculated: 303.1387 [M + Na]+,
319.1127 [M + K]+.
3,11ꢀDimethylꢀ6,8ꢀdioxaꢀ3,4,5,9,10,11ꢀhexaazatridecaꢀ4,9ꢀ
dienꢀ1ꢀolꢀ4,10 dioxide (4c). Yield 17%. Oil. IR (neat), ν/cm–1
:
1
3458, 2971, 2931, 2877, 1496, 1496, 1259, 1041, 944. H NMR
(CDCl3), δ: 1.10 (t, 6 H, 2 CH3C, J = 7.1 Hz); 2.35 (br.s, 1 H,
OH); 3.00 (s, 3 H, CH3N); 3.11 (s, 3 H, CH3N); 3.48 (q, 4 H,
2 CCH2N, J = 7.1 Hz); 3.51 (t, 2 H, CH2, J = 5.0 Hz); 3.78 (t, 2 H,
CH2, J = 5.0 Hz); 5.75 (s, 2 H, OCH2O). 14N NMR (CDCl3),
δ: –52.64. MS (ESI), m/z: 284.1676 [M + NH4]+, 289.1233
[M + Na]+, 305.0971 [M + K]+. C7H18N6O5. Calculated: 284.1677
[M + NH4]+, 289.1231 [M + Na]+, 305.0970 [M + K]+.
2,10ꢀDimethylꢀ1ꢀphenylꢀ5,7ꢀdioxaꢀ2,3,4,8,9,10ꢀhexaazaꢀ
dodecaꢀ3,8ꢀdienꢀ12ꢀolꢀ3,9 dioxide (4d). Yield 17%. Oil. IR
(neat), ν/cm–1: 3441, 2925, 1496, 1229, 1064, 1024, 939.
1H NMR (CDCl3), δ: 2.50 (s, 1 H, OH); 2.95 (s, 3 H, NCH3);
3.10 (s, 3 H, NCH3); 3.50 (t, 2 H, HOCH2, J = 5.0 Hz); 3.75
(t, 2 H, NCH2, J = 5.0 Hz); 4.55 (s, 2 H, NCH2Ph); 5.70 (s, 2 H,
OCH2O); 7.30 (s, 5 H, Ph). MS (ESI), m/z: 351.1385 [M + Na]+;
367.1117 [M + K]+. C12H20N6O5. Calculated: 351.1387 [M + Na]+;
367.1127 [M + K]+.
3ꢀMethylꢀ10ꢀ(piperidinꢀ1ꢀyl)ꢀ6,8ꢀdioxaꢀ3,4,5,9,10ꢀpentaꢀ
azadecaꢀ4,9ꢀdienꢀ1ꢀolꢀ4,10 dioxide (4f). Yield 16%. Oil. IR
(neat), ν/cm–1: 3474, 2944, 2859, 1498, 1445, 1227, 1171, 1069,
1
1035, 1018, 939. H NMR (CDCl3), δ: 1.50 (m, 2 H, C(4)H2,
J = 7.1 Hz); 1.75 (m, 4 H, 2 CH2); 2.60 (br.s, 1 H, OH); 3.10
(s, 3 H, CH3N); 3.40 (t, 4 H, 2 CH2, J = 7.1 Hz); 3.50 (t, 2 H, CH2,
J = 5.0 Hz); 3.75 (t, 2 H, CH2, J = 5.0 Hz); 5.85 (s, 2 H,
OCH2O). 14N NMR (CDCl3), δ: –53.45. MS (ESI), m/z:
315.1396 [M + Na]+, 331.1137 [M + K]+. C9H20N6O5. Calcuꢀ
lated: 315.1387 [M + Na]+, 331.1127 [M + K]+.
8ꢀMethylꢀ1ꢀ(morpholinꢀ4ꢀyl)ꢀ3,5ꢀdioxaꢀ1,2,6,7,8ꢀpentaazaꢀ
decaꢀ1,6ꢀdienꢀ10ꢀol 1,7ꢀdioxide (4g). Yield 12%. Oil. IR (neat),
ν/cm–1: 3387, 2939, 2885, 1504, 1443, 1334, 1286, 1176, 1068,
948, 666. 1H NMR (CDCl3), δ: 2.00 (br.s, 1 H, OH); 3.15 (s, 3 H,