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Sheremetev et al.
differential syntheses of electron density and then normalized on
the distance of 0.90 Å. All the hydrogen atoms were refined
using the riding model (Uiso(H) = nUeq(s,N), where n = 1.5 for
the carbon atoms of methyl groups, n = 1.2 for the N atoms).
1388, 1312, 1148, 1104, 1084, 1044, 1024, 984, 952, 932, 820,
760, 704. 1H NMR (DMSOꢀd6), : 1.49 (d, 6 H, CHMe2,
J = 6.1 Hz); 2.25 (s, 3 H, C(3)Me); 2.51 (s, 3 H, C(5)Me); 5.47
(septet, 1 H, CHMe2, J = 6.1 Hz); 6.26 (s, 1 H, C(4)H).
13C NMR (DMSOꢀd6), : 165.3 (C(1)); 158.5 (C(2)); 151.3 (C(5));
142.2 (C(3)); 109.8 (C(4)); 73.56 (CHMe2); 21.3 (CHMe2); 13.2,
12.9 (C(3)Me; C(5)Me).
3ꢀ(3,5ꢀDimethylpyrazolꢀ1ꢀyl)ꢀ6ꢀ(N,Nꢀdimethylamino)ꢀsꢀ
tetrazine (8d). The yield was 10%, red finely crystalline comꢀ
pound, m.p. 141—142 C (cf. Ref. 4: m.p. 137—138 C).
Found (%): C, 49.37; H, 6.00; N, 44.66. C9H13N7 (M = 219.25).
Calculated (%): C, 49.30; H, 5.98; N, 44.72. MS, m/z: 219 [M]+,
122, 106. IR, max/cm–1: 3146, 3101, 2922, 2871, 2798, 1573,
1488, 1411, 1399, 1368, 1296, 1207, 1131, 1076, 1038, 1021,
974, 948, 845, 810, 755, 611, 576, 531. 1H NMR (CDCl3), :
2.25 (s, 3 H, C(3)Me); 2.46 (s, 3 H, C(5)Me); 3.30 (s, 6 H,
NMe2); 6.02 (s, 1 H, C(4)H). 13C NMR (CDCl3), : 156.2 (C(1));
151.2 (C(5)); 143.9 (C(2)); 141.5 (C(3)); 104.1 (C(4)); 36.7
(NMe2); 8.5, 8.1 (C(3)Me, C(5)Me).
The refinement included 9138 independent reflections (Rint
=
= 0.0609), number of refined parameters was 448. Convergence
of refinement for all the independent reflections wR2 = 0.1115,
GOOF = 1.014 (R1 = 0.0478 on 6163 reflections with I > 2(I)).
All the calculations were performed on IBM PC AT using the
SHELXTL program package.40 The structure was deposited with
the Cambridge Structural Database (CCDC 852363).
Preparation of N´ꢀ[6ꢀ(3,5ꢀdimethylpyrazolꢀ1ꢀyl)ꢀsꢀtetrazinꢀ
3ꢀyl]ꢀ4ꢀmethylfurazanꢀ3ꢀcarbohydrazide 5a in different solvents
(general procedure). A mixture of tetrazine 1a (0.27 g, 0.1 mmol)
and hydrazide 2a (0.14 g, 0.1 mmol) in the corresponding solꢀ
vent 10 mL) was stirred on heating until the reaction reached
completion (TLC monitoring, eluent CCl4—MeCN (3 : 1)). The
method for the isolation of product 5a depends on the type of
solvent used. For the reaction conditions and the product yields,
see Table 1. The data for compound 5a are summarized in Table 4.
A. When the reaction was carried out in alcohols and DMF,
formation of two product was observed. The starting comꢀ
pounds and the reaction products are well detectable by TLC:
Rf(8) > Rf(1) > Rf(2) > Rf(5). The reaction mixture was cooled
to 20 C and diluted with water (10 mL). An orange precipitate
formed was filtered off, washed with hexane (15 mL), and reꢀ
crystallized from the PriOH—H2O (1 : 1) mixture. The filtrate
was extracted with hexane (30 mL), the solvent was evaporated
to obtain a mixture of tetrazine 8a—d and 3,5ꢀdimethylpyrazole,
which was separated by column chromatography on SiO2 (eluent
dichloromethane).
B. When the reaction was carried out in THF, nitromethane,
benzene, or dioxane, no formation of side products was observed.
After the reaction was completed, the solvent was evaporated to
dryness, and the residue was recrystallized from PriOH—H2O
(1 : 1).
C. When the reaction was carried out in glyme or DMSO
(the reaction mixture was diluted with water (10 mL)), an orꢀ
ange precipitate formed was filtered off, washed with water
(2×3 mL), and recrystallized from PriOH—H2O (1 : 1).
D. After reflux in chloroform for 54 h, the reaction mixture
still contained about half of unreacted starting compounds. The
reaction mixture was cooled to 20 C, a formed precipitate of
product 5a was filtered off and recrystallized. The filtrate conꢀ
taining the starting compounds 1a and 2a was concentrated to
dryness. The residue was dissolved in hot EtOH (2 mL), the
solution was cooled to –5 C; a white precipitate formed was
filtered off to obtain methylfurazancarboxylic hydrazide 2a. The
filtrate was concentrated to dryness, and the residue was reꢀ
crystallized from PriOH—H2O (7 : 1) to yield the starting tetrꢀ
azine 1a.
3ꢀ(3,5ꢀDimethylpyrazolꢀ1ꢀyl)ꢀ6ꢀmethoxyꢀsꢀtetrazine (8a).
The yield was 29%, pink solid compound, m.p. 157—158 C
(cf. Ref. 4, m.p. 156—157 C). Found (%): C, 46.67; H, 4.93,
N, 40.71. C8H10N6O (M = 206.20). Calculated (%): C, 46.60,
H, 4.89, N, 40.76. MS, m/z: 206 [M]+ 121, 106, 94, 80, 67. IR,
max/cm–1: 3112, 3024, 2960, 2924, 1644, 1576, 1484, 1448,
1400, 1376, 1356, 1280, 1160, 1136, 1084, 1048, 1028, 1000,
972, 952, 824, 760, 680, 588, 572. 1H NMR (DMSOꢀd6), : 2.25
(s, 3 H, Me, C(3)); 2.50 (s, 3 H, Me, C(5)); 4.27 (s, 3 H, OMe);
6.29 (s, 1 H, H, C(4)). 13C NMR (DMSOꢀd6), : 166.1 (C(1));
158.8 (C(2)); 151.5 (C(5)); 142.4 (C(3)); 110.1 (C(4)); 56.78
(OMe); 13.0, 13.3 (C(5)Me; C(3)Me). 15N NMR (DMSOꢀd6),
: 293.1, 301.6, 353.5, 373.2.
3ꢀ(3,5ꢀDimethylpyrazolꢀ1ꢀyl)ꢀ6ꢀethoxyꢀsꢀtetrazine (8b). The
yield was 20%, pink amorphous compound, m.p. 114—115 C.
Found (%): C, 49.13; H, 5.55, N, 38.08. C9H12N6O (M =
= 220.23). Calculated (%): C, 49.08: H, 5.49: N, 38.16. MS, m/z:
220 [M]+ 121, 106, 94, 80. IR, max/cm–1: 3104, 2988, 2964,
2932, 1576, 1484, 1432, 1388, 1348, 1328, 1280, 1112, 1088,
1024, 988, 968, 952, 932, 828, 764, 660. 1H NMR (DMSOꢀd6),
: 1.49 (t, 3 H, CH2CH3, J = 7 Hz); 2.25 (s, 3 H, C(3)Me); 2.50
(s, 3 H, C(5)Me); 4.65 (q, 2 H, CH2Me, J = 7 Hz); 6.28 (s, 1 H,
C(4)H). 13C NMR (DMSOꢀd6), : 165.7 (C(1)); 158.7 (C(2));
151.5 (C(5)); 142.3 (C(3)); 110.0 (C(4)); 65.8 (OCH2Me); 14.13
(OCH2CH3); 13.4, 13.0 (C(3)Me; C(5)Me).
E. When the reaction was carried out in water, it was stopped
after heating tetrazine 1a and hydrazide 2a for 55 h at 80 C
(according to the TLC data, the reaction mixture still contained
much of the starting compounds). The mixture was cooled to
20 C, the poorly soluble in water compounds 1a and 2a were
filtered off, the aqueous filtrate was extracted with dichloꢀ
romethane (10 mL), whose concentration gave product 5a. The
aqueous solution after acidification with 1% HCl (3 mL) and
extraction with diethyl ether (2×10 mL) furnished 3ꢀ(3,5ꢀdiꢀ
methylpyrazolꢀ1ꢀyl)ꢀ6ꢀhydroxyꢀsꢀtetrazine (8e), the yield was
11%, dark red solid compound, m.p. 205 C (with decomp.).
Found (%): C, 43.82; H, 4.16; N, 43.67. C7H8N6O (M = 192.18).
Calculated (%): C, 43.75; H, 4.20; N, 43.73. IR, max/cm–1
:
3136, 3088, 3036, 2900, 1744, 1708, 1692, 1552, 1508, 1432,
1404, 1372, 1264, 1160, 1140, 1104, 1064, 1024, 992, 976, 836,
808, 780, 764. 1H NMR (DMSOꢀd6), : 2.25 (s, 3 H, C(3)Me);
2.39 (s, 3 H, C(5)Me); 6.20 (s, 1 H, C(4)H). 13C NMR (DMSOꢀd6),
: 152.0 (C(1)); 150.6 (C(5)); 147.7 (C(2)); 141.9 (C(3)); 108.8
(C(4)); 13.21 12.11 (C(3)Me; C(5)Me).
F. When the reaction was carried out in ionic liquid, a mixꢀ
ture of [emim][BF4] (3 mL), tetrazine 1a (0.1 g, 0.37 mmol),
and hydrazide 2a (0.05 g, 0.37 mmol) was heated for 24 h at
3ꢀ(3,5ꢀDimethylpyrazolꢀ1ꢀyl)ꢀ6ꢀ(isoꢀpropoxy)ꢀsꢀtetrazine
(8c). The yield was 5%, light pink amorphous compound, m.p.
47—48 C. Found (%): C, 51.36; H, 6.07; N, 35.80. C10H14N6O
(M = 234.26). Calculated (%): C, 51.29; H, 6.02; N, 35.88. MS,
m/z: 234 [M]+ 121, 106. IR, max/cm–1: 2976, 2928, 1576, 1476,